Biomedical subjects
Publications and source records attributed to T Klein.
Hip synovitis plays a part in many rheumatic diseases. In the young adult acute arthritis may be due to reaction to trauma, infection or gout. Although transient synovitis of the hip is a well-known phenomena in children the condition is not well-documented in adults. We present 10 young adults with idiopathic transient synovitis of hip who had attended the Soroka Medical Centre between 1986 and 1990.
Sleep disturbances and the failure to entrain circadian rhythms to the 24-hour day have been reported in the majority of totally blind subjects. The present case study of a totally blind man with a well-documented recurring sleep disturbance was designed to investigate the mutual relationship between sleep and the circadian timing system. The 63-year-old subject, a high school teacher with a regular work schedule, had suffered from cyclically recurring insomnia for the past 28 years. Analysis of a sleep log that he had kept for the past 15 years suggested that his circadian rhythms were not entrained to the 24-hour day. During a 3-month inpatient study, the period of the endogenous circadian pacemaker was assessed by analysis of ambulatory core body temperature, urinary excretion and a series of estimates of the phase of core body temperature cycles and plasma cortisol levels during constant routines. All circadian markers revealed periods in the range of 24.22-24.27 hours, with no evidence for a modulation of the observed periods by the sleep-wake cycle. During this 3-month inpatient study, a complete cycle of the subject's sleep disturbance and remission was polysomnographically documented while the subject lived on a regular 24-hour schedule. Because the subject's circadian rhythms were free-running and his sleep times were fixed, sleep occurred at virtually all circadian phases. Analysis of sleep latency, REM sleep latency, sleep duration, wake in sleep episode and REM sleep during sleep episode revealed a strong modulation by circadian phase. These findings in this blind man suggest that: 1) the period of his cyclically recurring sleep disturbance is directly related to the nonentrained period of an endogenous circadian pacemaker that drives circadian variation in core body temperature, urinary excretion, plasma cortisol and sleep propensity; 2) both his sleep structure and the severity of his daily sleep disruption are directly related to circadian phase and 3) his circadian pacemaker, which has an endogenous period that deviates only 0.2-0.3 hours from 24 hours, cannot be entrained by periodic daily exposure to nonphotic time cues, including a very regular 24-hour sleep-wake schedule.
METHOD: Forty-eight parents and 172 children were typed for class I HLA antigens, locus A,B. RESULTS: Although the number of cases is small, we observed: (1) a significantly decreased number of sons born after a first delivery of a son, as compared to a first delivery of a daughter; (2) significantly increased sharing of maternal class I HLA antigens between the firstborn son and his brothers from higher birth orders, as compared to his sisters; and (3) HLA-A2 antigen, which is known to be involved in HLA restricted cytotoxic reactions in the recognition of minor histocompatibility antigens, was inherited in subsequent deliveries of sons as compared to daughters in a significantly higher frequency from the paternal than from maternal HLA haplotype. The results suggest that sharing of identical maternal HLA haplotypes between brothers may aid to decrease the degree of maternal sensitization to fetal antigens, and lack of HLA-2 antigen in maternal cells from sons as compared to daughters may avoid maternal HLA-A2 restricted cytotoxic reactions toward the male fetus.
"Life expectancy and mortality increasingly are analyzed in the context of social factors. This study analyzes the impact of social position, marital status, and religious confession on cohort life expectancy. The analysis is based on [German data from the] Socio-Economic Panel Survey, wherein proxy-interviewee's parents have been used to estimate cohort mortality. Results confirm a lower mortality risk of the upper classes and of married persons. However, as opposed to other studies, Catholics do not have a lower, but even a higher mortality risk." (SUMMARY IN ENG)
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Many methods for analyzing biological problems are constrained by problem size. The ability to distinguish between relevant and irrelevant features of a problem may allow a problem to be reduced in size sufficiently to make it tractable. The issue of learning in the presence of large numbers of irrelevant features is an important one in machine learning, and recently, several methods have been proposed to address this issue. A combination of machine learning approaches and statistical analysis methods can be used to identify a set of relevant attributes for currently intractable biological problems. We call our framework F/I/E (Focus-Induce-Extract). As an example of this methodology, this paper reports on the identification of the features of mutations in collagen that are likely to be relevant in the bone disease Osteogenesis imperfecta.
Therapeutic drug monitoring of 5-FU was investigated in patients with head and neck cancer treated with cisplatin (100 mg/m2) followed by 5-day continuous infusion of 5-FU (1 g/m2/d). In a first step, the 5-FU pharmacokinetic and pharmacodynamic analysis of 25 cycles for 14 patients revealed that both the time-concentration product (ASC) for the entire cycle and the half-cycle were predictive of cycle toxicity and a dose adjustment diagram was established. In a second experiment, this diagram was used for treatment monitoring in a group of 35 patients (97 cycles). The clinical toxicity and response were compared with those of a retrospective group of 55 patients (184 cycles) treated with the same protocol without dose adjustment. Pharmacokinetic follow-up of 5-FU has proved to be an objective means to significantly reduce haematological and/or digestive tract toxicity (47 to 33%). Moreover, although dose reduction was often performed, the clinical response was not affected (42-44%), neither was the median survival time (8.8 months-14.1 months in control and adapted groups respectively).
It is suggested that tubulointerstitial nephritis and uveitis (TINU) is a cell-mediated immune disease with a favourable response to treatment with steroids. However, long-term follow-up has not been described and data on immunological studies are limited. The aim of this study was to evaluate the clinical features in patients with TINU who have had a long follow-up period, and in parallel to assess their cellular immunity and HLA typing. Four women with TINU were followed for 5.7 +/- 3.6 years. On remission they were studied for T-cell-mediated immunity by skin tests, T-cell subpopulations, and lymphokine secretion in vitro. The lymphokines included interleukin-2, gamma-interferon, tumour necrosis factor, and colony-stimulating factor. The in vitro response to AS101, a previously described immunomodulator, was evaluated. HLA-typing was also performed. The nephritis, which occurred once, was resolved in all patients and did not recur. In contrast, numerous relapses of uveitis occurred despite topical or systemic steroid treatment. The patients' T-cell subpopulations did not differ from controls, but they revealed anergy to skin tests and a very low secretion rate of lymphokines. AS101 corrected the suppressed secretion in vitro. A high frequency of HLA-DR6 antigen was found in the TINU patients. TINU is probably a systemic disease with a chronic relapsing course of the uveitis but with complete clinical recovery of the nephritis. Both in vivo and in vitro T-cell functions are suppressed during remission.
Life expectancy in Germany has increased considerably during the 20th century. Simultaneously a considerable change in occupational structure has occurred. Keeping the occupational impact on mortality in mind, the question arises as to what extent the mortality decrease can be contributed to changes in occupation. Based on cohort data this question is analysed with the result that a considerable impact on life expectancy is confirmed. The impact of changes in occupational structure on life expectancy is greater for men than for women. This can be explained by the fact that men benefit from the improvements of general living conditions associated with occupational status, as well as from improved working conditions.
Attitudes toward Special Olympics were examined in a group of 41 experts in the field of mental retardation and 40 parents of participants in the Special Olympics program. Experts completed a 15-item questionnaire that included Likert-type items regarding possible Special Olympics goals and their importance and fulfillment and open-ended questions regarding program benefits, strengths and weaknesses. Experts were also asked how the program might fit into the normalization debate. Parents were given a similar survey that also included child and parent participation questions. Generally, both groups viewed the program as highly beneficial, particularly in terms of social adjustment and life satisfaction. As to concerns cited, some experts noted potentially segregative aspects of the program, whereas parents focused on administrative issues.
Using Escherichia coli K-235 as a production strain in a fed-batch fermentation process with an optimized sorbitol/yeast extract medium, we were able to produce 640 U of CMP-Neu5Ac synthetase in 10 l scale (64 U/l) and 9200 U (total enzyme) in 200 l scale (390 U/kg wet weight). By simple one-step purification procedures, enzyme preparations were obtained that could be used efficiently for the synthesis of CMP-Neu5Ac from CTP and Neu5Ac with over 90% yield, from Neu5Ac, CMP, and ATP or phosphoenolpyruvate by in situ generation of CTP, and from CTP, pyruvate, and ManNAc or GlcNAc by in situ generation of Neu5Ac.
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The HLA typing profile of 26 Israeli subjects with recurrent aphthous stomatitis (RAS) was examined and compared with that of 100 healthy control subjects. HLA-B51 was found in six subjects (23%) with RAS and in nine control subjects (9%) (p < 0.05). HLA-Cw7 was found in six subjects with RAS (23%) and in five control subjects (5%) (p < 0.01). Eleven subjects had first-degree relatives who had RAS. Because a high frequency of HLA-B51 has been found in Behcet's syndrome and aphthous stomatitis is part of this syndrome, it is suggested that in some subjects with RAS the entire syndrome may actually develop in the future.
Legionella pneumophila is an opportunistic intracellular pathogen that infects macrophages, both in vivo and in vitro. Tetrahydrocannabinol is a major psychoactive component of marijuana and can affect the functional activity of macrophages. In the present study, it was found that the treatment of macrophage cultures from permissive A/J mice with THC enhanced the growth of Legionella in these cells. Legionella grew much better in macrophages treated with low doses of THC, which caused no alteration in the number or viability of macrophages, as compared with growth in untreated cells. Furthermore, lipopolysaccharide-treated A/J mouse macrophages restricted the growth of Legionella, but this growth restriction was overcome by the addition of THC to LPS-treated macrophage cultures after infection. Thus, it is apparent that THC has the ability to enhance the growth of the intracellular opportunistic pathogen Legionella that grows in A/J mouse macrophages.
The authors analyze clinical and laboratory aspects of Indomethacin treatment of neonates with a patent ductus arteriosus. From June 1987 to November 1990 the authors treated 19 neonates with a patent ductus arteriosus with Indomethacin. The drug was administered, 0.1-0.3 mg/kg body weight, by the oral route three times/24 or 36 hours. In 17 infants after Indomethacin treatment the duct closed, in two infants the duct did not close during Indomethacin treatment, in three infants the authors observed oliguria which improved after discontinuation of treatment.
The expression of class I histocompatibility antigens (HLA) in transitional cell carcinoma of the bladder was studied by the immunoperoxidase technique and correlated with tumor differentiation and survival. Tumors of 33 patients who underwent cystectomy were examined; 57% of the tumors expressed HLA class I antigens. Positive expression was observed in 5 of 6 cases with Grade 1 tumors, 8 of 13 with Grade 2, and 6 of 14 with Grade 3. The 5-year survival was significantly better in patients with HLA class I-positive tumors (74%) compared with those with negative tumors (36%, P less than 0.05). The expression of HLA class I on tumor cells may serve as a target for the immune response and control the metastatic potential of the tumor. These results suggest that HLA class I expression in bladder carcinoma is a prognostic indicator that should be considered in treatment planning.
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Serum beta-2 microglobulin (B-2M) levels were studied in 365 breast cancer patients and 210 age-matched controls. The patients were divided into three groups: Group A, new patients at diagnosis; Group B, patients at follow-up; and Group C, metastatic patients. The mean B-2M of all breast cancer patients plus or minus one standard deviation (3.5 +/- 1.2; range, 1.1 to 5.9) was significantly higher than normal controls (1.29 +/- 0.49; range, 0.3 to 2.3; P less than 0.005). When the three patient groups were compared with each other, the mean B-2M level of Group A (3.0 +/- 1.5; range, 0.9 to 6.9) was similar to that of Group C (4.22 +/- 1.1; range, 2.0 to 6.4). The mean B-2M of both Groups A and C was significantly higher than that of Group B (2.38 +/- 1.02, range, 0.4 to 5.4; P less than 0.001). In Group A the mean B-2M decreased significantly after a 12-month period and reached the mean level of Group B but not that of normal controls. When patients in Group B were analyzed by their stage of disease at diagnosis, there was no significant difference between Stages I and II. There was a significant difference in the mean B-2M levels between Stages I and III. In relapsing patients, mean B-2M levels increased. These findings suggest that serum B-2M levels may reflect tumor burden, and even in patients at follow-up, occult tumor cells may activate the immune system.