Biomedical subjects
Publications and source records attributed to M Silbermann.
Trends in the incidence of classic Kaposi's sarcoma in the Jewish population in Israel for the period between 1960 and 1998 were analysed. World standardised incidence rates of 20.7 and 7.5 per million among men and women, respectively, were calculated. The highest incidence rates were displayed by men originated from Africa and by Asian-born women.
Reliable information about comparative cancer incidence in the Middle East has been lacking. The Middle East Cancer Consortium (MECC) has formed a network of population-based registries with standardized basic data. Here the age-adjusted cancer incidences are compared for four populations: Israeli Jews, Israeli non-Jews, Jordanians and the US Surveillance Epidemiology and End Results (SEER) population, for the years 1996-1997 (Israel) and 1996-1998 (other populations). The all-sites rate of cancer is approximately twice as high in Israeli Jews and SEER, compared with Israeli non-Jews and Jordanians. Rates of lung cancer are similar among Israeli Jews and non-Jews and about twice as high as in Jordanians. Childhood leukaemia rates in Jordan are higher than in Israeli Jews, but lower than SEER. Hodgkin lymphoma rates in Israeli non-Jews and Jordanians are similar to SEER, but non-Hodgkin lymphoma rates are lower than SEER. The previous suspicion of higher overall leukaemia and lymphoma rates in Jordan is thus not confirmed.
BACKGROUND: To evaluate and compare differences in the molecular genetics among high-risk (Ashkenazi Jews), intermediate-risk (Sephardic Jews) and low-risk (Palestinians) groups for colorectal cancer who live in the same geographical region. PATIENTS AND METHODS: The 1995-1996 records from the Tel Aviv Medical Center and Muqased hospital (East Jerusalem) randomly identified patients with colorectal cancer. There were 25 patients from each ethnic group. Epidemiological data were obtained from interviews with the patients and from their hospital charts. The levels of cyclin D1, beta-catenine, p27, p53, Ki-67 and Her-2/neu proteins were determined by immunohistochemistry. The main outcome measures were the association between gene expression and colorectal incidence in the different ethnic groups. RESULTS: Ashkenazi Jews have the highest rate of colorectal cancer, and are diagnosed at an early stage compared with Palestinians (72% and 33% of the cases are in Dukes' A and B, respectively), and, hence, this may explain the better 5-year survival rate among this group. Sephardic Jews are diagnosed at a more advanced stage, the tumors are poorly differentiated and they lack p27. Palestinians have significantly higher cyclin D1 levels. There was a statistically significant inverse correlation between the expression of beta-catenine and cyclin D1, as well as p53 and p27 (P <0.05). CONCLUSIONS: Increased expression of cyclin D1, p53, Ki-67, beta-catenine and Her-2/neu, and decreased expression of p27 may be important events in the three ethnic groups with colorectal cancer. The lower mortality rate among Ashkenazi Jews may be partially explained by their better molecular biology profile.
Obstructive sleep apnea (OSA) is a common disorder of the middle aged and elderly. It results from the decrease in upper airway muscle (UAM) tone that occurs during sleep. It is unclear whether age-related changes in UAM could constitute a contributory mechanism to the increased prevalence of OSA with increasing age, and previous papers evaluating the effects of aging on UAM in rats reported conflicting results. In the present study, we compared, in four age groups of Wistar rats (6-24 months), fiber-type distribution, mean cross-sectional fiber area and succinate dehydrogenase optical density of dilating and non-dilating UAM, and the diaphragm. Succinate dehydrogenase optical density, a marker of oxidative capacity, decreased significantly after the age of 6 months in all muscles (except for the sternohyoid), particularly in the genioglossus, the main tongue protrudor. In this muscle, we also found a significant decrease in type IIa and an increase in IIb fibers after the age of 18 months. Age-related changes in fiber-type distribution in other muscles were mostly insignificant. Dilating UAM could not be distinguished from their non-dilating neighboring muscles by their histochemical properties or aging-related changes. The aging-related changes observed in the present study may decrease UAM endurance, particularly that of the main tongue protrudor, the genioglossus.
This project signals an advance in cancer registration in the Middle East region. While it is too early to declare a major breakthrough, significant strides have been made toward establishing a basis for reliable information on the cancer burden at a population level and future collaborative efforts in cancer epidemiologic research and prevention.
OBJECTIVES: To investigate the effects of different levels of hormones on the ciliary activity of human oviducts and, consequently, to assess their possible role in tubal implantation of the fertilized egg. DESIGN: Fallopian tube epithelial samples were incubated in media with the addition of Estradiol (E2), progesterone (P), human menopausal gonadotropin (hMG), LH, or pure FSH (Metrodin) in different concentrations. The ciliary beat frequency (CBF) was measured after 24 h of incubation. Then the media were exchanged to media without the addition of hormones and the CBF was measured again 24 h later by using the photoelectric technique. SETTING: University teaching hospital, IVF unit. RESULTS: Twenty-four hr after the addition of P to the culture medium in concentrations of 0.5 or 1 ng/ml a significant decline of the CBF down to 63% of the control level was observed (P < 0.001) and with P in concentration of 2 ng/ml or greater, 50-70% of the cilia were paralyzed. These effects of P were found to be reversible. Incubation with E2 induced a slight increase of 4% in the mean CBF (P = 0.002). Twenty-four hr incubation with Metrodin, Pergonal, or LH did not affect ciliary motility. CONCLUSIONS: Higher levels of progesterone cause ciliary dysfunction and subsequently may be a possible cause of ectopic pregnancy.
Asthma is among the most frequent chronic diseases in childhood. Although numerous environmental risk factors have already been identified, the basis for familial occurrence of asthma remains unclear. Previous genome screens for atopy in British/Australian families and for asthma in different American populations showed inconsistent results. We report a sib pair study of a sample of 97 families, including 415 persons and 156 sib pairs. Following an extensive clinical evaluation, all participants were genotyped for 351 polymorphic dinucleotide markers. Linkage analysis for asthma identified four chromosomal regions that could to be linked to asthma: chromosome 2 (at marker D2S2298, P = 0.007), chromosome 6 (around D6S291, lowest P = 0.008), chromosome 9 (proximal to D9S1784, P = 0.007), and chromosome 12 (D12S351, P = 0.010). These linkage regions could be reproduced for all loci by analysis of total or specific immunoglobulin E (minimum P values at these regions were 0. 003, 0.001, 0.010, and 0.015, respectively).
The cartilage-flow phenomenon has been frequently described but not in connection with transplantation procedures for treatment of cartilage lesions. Consequently, we examined this particular phenomenon in an experimental sheep model originally set up to study the use of perichondrial grafts for repair of full-thickness cartilage lesions. Osteochondral lesions were made in nonweight-bearing and weight-bearing areas of knee joints in 36 sheep. The defects were filled with autologous rib perichondrial grafts and secured by either collagen sponges or fibrin glue (n = 24 animals). Defects without perichondrial grafts served as controls (n = 12 animals). Following 1 week of immobilisation of the operated leg, the plaster was removed, and animals were allowed to move freely. Animals were killed after 2, 4, 12 and 16 weeks. Grafts including rims of original surrounding cartilage and bone were removed and investigated by means of macroscopy, histology and micromorphology, including scanning electron microscopy and analysis under polarized light. Cartilage flow was observed in all specimens by 4 weeks after drilling the defects, independent of the weight-bearing condition. These flow formations exhibited a bending of the collagen fibres centrally into the defects, reduction of metachromasia, cell cluster formation and areas of reduced cell density. Time-dependent flow formations were observed related to the weight-bearing condition and whether or not the defects had been grafted. In grafted, non-weight-bearing defects further cartilage flow was stopped 8 weeks after transplantation by the growing perichondrial transplants, which had filled the defects completely. In contrast, control defects exhibited further flow formations in both areas. The same was observed in grafted defects in the weight-bearing area. In defects without complete filling as not enough spontaneously growing fibrous tissue had arisen from the bottom of the defects, two different observations were made: either the defects exhibited a fungiform mass of fibrous tissue that had overgrown the lateral flow formations, or the central mass of fibrous tissue was overgrown by the lateral flow formations. In conclusion, cartilage flow seems to be a mechanically induced phenomenon at the rims of cartilage lesions that contributes little to the reduction of size of large osteochondral defects. There was no evidence for new cartilage proliferation or production of cartilaginous matrix at the rims of the lesions.
To assess the long-term effect of vitamin D or calcium supplementation on the skeletal metabolism of aging laboratory rodents, 1.5-month-old female Wistar rats were fed with diets containing twice the concentration of vitamin D (group 2) and of calcium (group 3) as in the usual rat chow. Follow-up to 24 months of age did not show significant differences between the enriched-diet groups and the controls (group 1) in terms of the vertebral body weight and protein content. Significantly higher bone mineral contents were found in groups 2 and 3 than were found in controls, as revealed by an increased bone mineral density (BMD: +62%, group 2; +48%, group 3) and vertebral calcium content (+73%, group 2; +84%, group 3). The vertebral alkaline phosphatase enzymatic activity was significantly lower in the enriched diet groups than in controls (-47%, group 2; -45%, group 3). The ratio alkaline phosphatase/acid phosphatase activity was markedly reduced in groups 2 and 3 (-57% and -59%, respectively), which might indicate a diminished rate of bone turnover. The trabecular bone volume (BV/TV) decreased in all groups during senescence, being significantly elevated in group 3 as compared to controls. Vitamin D and calcium dietary supplementations increase the axial mineral bone content in laboratory rats and might reduce the bone turnover. Their influence on the trabecular bone volume has yet to be examined.
The effect of 17 beta-estradiol and progesterone on ocular lens in rats and untreated controls was studied. In the treated lenses, the activity of hexokinase and glucose-6-phosphate dehydrogenase remained unchanged. The activity of aldolase was increased in 18- and 20-month-old lenses as compared to controls. Aldose reductase activity was decreased at the age of 20 months (p < 0.001). Structural lens proteins studies by SDS polyacrylamide gel electrophoresis and immunodecoration with specific antibodies for crystallines alpha A + alpha B and beta + gamma suggest some protective effect in treated animals.
The main objective of this research was to study the relationship between glucocorticoids, aging and the deterioration of cognitive functions. Towards this end, an attempt was made to develop an animal model which will enable the investigation of such interactions, using subcutaneously implanted sustained-release corticosterone pellets. The goal was to achieve moderately high concentrations of corticosterone in plasma, comparable to the peak basal levels or to those found under mild stress. Middle-aged (12 months old) Fischer-344 rats, used in this study, were divided before the prolonged hormonal treatment into cognitively 'impaired' and 'non-impaired' groups using the Morris water maze. The cognitive impairment, which was induced by the long-term corticosterone administration, was exhibited during acquisition of the 8-arm radial maze only in the 'non-impaired' group. Behavioral scores for drug-treated 'impaired' rats were not statistically different from those of the placebo-treated 'impaired' group. The morphological deterioration in hippocampal areas of the brain was quantified and revealed high correlation with the behavioral data. This animal model may become extremely useful in testing projected prophylactic therapy against the brain damage and cognitive deficits induced by the high corticosteroid-aging combination.
Cognitive and memory capacities were assessed in two strains of rats of various age groups prior to histological evaluation of their brains. Male Wistar rats, at the age of 3, 12, 17 and 24 months, were tested using the 8-arm radial maze and male Fischer 344 rats, aged 3, 12 and 16 months, were tested in the Morris water maze. Significant memory impairments were found in both strains already at the age of 12 months in about 50% of the population. Morphological analysis of the brains revealed age-related structural changes in the hippocampal formation starting with the middle-age group. Degenerative CA1 and CA3 pyramidal cells characterized the hippocampus of cognitive-impaired rats, while non-impaired animals exhibited intact hippocampus irrespective of age. This characteristic was supported by quantitative morpho-analysis. The best correlation between the decrease of area or number of cells and working memory impairment was found for CA3 region in both strains. Age-related decline in the density of muscarinic receptors in Wistar rats' brain corresponded with the pattern of cognitive deficit. The results of the present study support the hypothesis which associates hippocampal integrity with normal memory function. It is concluded that chronological age by itself is not an adequate indicator of age-related brain alterations and individual evaluation of performance, based on behavioral scores, is recommended.
The effectiveness of autologous rib perichondrium for repair of full-thickness hyaline cartilage defects has been shown experimentally and clinically in various reports. The purpose of this study was to examine the behaviour of sheep rib perichondrial tissue under in vitro conditions and the influence of different culture matrices in order to evaluate possible stimulating effects. Rib perichondrium was obtained from sheep used for an experimental in vivo trial. After removal of adjacent cartilage remnants the tissue was divided and specimens cultured for 14 days in different ways. Explants cultured on collagen sponges (group A), fibrin glue (group B) and cellulose acetate filter (group C) were examined histologically, histochemically, histomorphometrically and autoradiographically. Clear differentiation of perichondrial cells towards a chondrocyte-like cell shape, particularly in the proliferation zone, was noticed on all matrices. These cells synthesized new matrix substances comparable to the ground substance normally present in hyaline cartilage. Morphometric comparison of tissue differentiation on different culture matrices revealed no significant differences in proliferation rates.
Cartilage tissue from embryonic mice which undergoes osteogenic differentiation during in vitro cultivation was used to study the effect of osteosarcomagenic doses of alpha-irradiation and bone-tumor-inducing retroviruses on proliferation and phenotypic differentiation of skeletal cells in a defined tissue culture model. Irradiated mandibular condyles showed dose-dependent enhancement of cell proliferation at day 7 of the culture and increased osteogenic differentiation at day 14. Maximal effects were found with 7.4 Bq/ml of 224Ra-labeled medium. Doses of 740 and 7400 Bq/ml of 224Ra-labeled medium induced increasing cell death. Retrovirus infection enhanced osteogenic differentiation and extended the viability of irradiated cells. After transplantation none of the treated tissues developed tumors in syngeneic mice.
Recently it has been demonstrated that long-term administration of GH leads to increase of skin thickness. The aim of the present study was to determine whether this effect of GH is mediated by insulin growth factor 1 (IGF-1), which enhances epidermal proliferation. In order to address this question, human split-thickness grafts obtained from aged skin were grafted onto nude mice. One group of mice was treated systemically with GH, whereas a second group was treated with intradermal graft injections of anti-IGF-1 in addition to GH. A third group received distilled water and served as a control group. Histological and autoradiographic analyses were performed before and after engraftment. The GH-treated mice showed a significant increase in epidermal proliferation measured by epidermal thickness (analysis of variance with repeated measurements, P < 0.01) and labeled index (analysis of variance, P < 0.01) as compared to the control group. The intradermal injections of anti-IGF-1 reduced significantly the proliferative stimulatory effect of GH (P < 0.01). The present study emphasizes the role of IGF-1 in the increased skin thickness observed after GH administration and provides a useful model for determining the effect of various compounds, including GH, on human skin.
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A clinico-biochemical study indicated that the beta-blocker DL-propranolol may affect human lens epithelial hexokinase (HK) activity. In that study five key enzymes were analysed in 192 freshly excised human lens epithelia obtained during cataract surgery. In a large number of patients the epithelial HK was found to be inactive. Medical records of these patients showed widespread use of the drug DL-propranolol. In vitro experiments demonstrated a direct inhibitory effect of the drug on human lens HK activity. Lens refractive function was monitored during long term bovine lens culture experiments in which the potential cataractogenic agent was added to the culture media. DL-propranolol in a concentration of 0.1 mM reduced HK activity in bovine lens epithelium after 72 hr in organ culture and disrupted lens light focusing ability after 250 hr of incubation. Kinetic studies of HK inhibition suggested a competitive inhibitory effect of the drug on the enzyme.
Condylar cartilages were cultured in the form of organ cultures on top of collagen sponges in medium containing 2% fetal calf serum and were treated with 3.5-350 nM insulin for 6 days. Doses of 175 nM of insulin caused a marked increase (+96%) in DNA synthesis and in proteoglycan production (+74%), features that manifested themselves structurally by a 60% increase in overall size of the cultured explants. Using a tissue culture system comprised of cartilage progenitor cells, insulin was found to enhance the differentiation of the progenitor cells so that by 6 days in culture an appreciable nodule of differentiated chondrocytes developed. The latter was surrounded by perichondrial cells whereas the extracellular matrix within the newly formed, insulin-induced, nodule reacted positively for cartilage-specific antigens (type II collagen and bone sialoprotein). It is suggested that insulin induces a direct stimulatory effect on progenitor cell proliferation, cartilage differentiation, and extracellular matrix deposition.