S-laminin and N-acetylgalactosamine located at the synaptic basal lamina of skeletal muscle are involved in synaptic recognition by growing neurites

Summary The purpose of the work reported here is to identify molecular components of the synaptic basal lamina of skeletal muscle fibres which allow recognition of original synaptic sites by regenerating motor axons. We focused on s-larninin and components recognized by the lectinDolichos biflorus agglutinin previously shown to be specifically located at the synaptic basal lamina. We used a cryoculture bioassay in which chick ciliary ganglion neurons grow on rat skeletal muscle cryostat sections. In control cultures, neurites extended over the muscle sections in close association with the muscle cell surface. It was observed that most of the neurites that extended towards the endplate zone and reached an area of 40 m around the neuromuscular junction ceased to grow when they contacted the synaptic site. Masking either lectin receptors or some s-laminin molecule epitopes prior to the culture of neurons alters the behaviour of growing neurites. On sections treated either withDolichos biflorus agglutinin or anti s-laminin monoclonal antibodies (D5 and C4) most of the neurites did not stop their growth at the synaptic regions. Moreover, treating muscle sections withDolichos biflorus agglutinin removed the gradient of substratum affinity around the endplate. These results indicate that the s-laminin andDolichos biflorus agglutinin receptors present on muscle cell surfaces may play a functional role in the interaction of growing neurites with original synaptic sites in the process of neuromuscular regeneration.     

100 years of x-rays: increase in image quality of intra-oral radiographs, decrease in patient exposure

Comparing a present-day bitewing radiograph with one of the first dental radiographs made immediately after the discovery of the X-rays, we can see how enormously the image quality of dental radiographs has improved. Besides the improved image quality, patient exposure has decreased considerably during the past 100 years. Improvement of image quality and reduction of patient exposure have been brought about by changes of X-ray equipment and radiographic films. These changes, which have led to a better image quality and a decrease of patient exposure during the past 100 years, are discussed in this article.     

Microdissection and microcloning of chromosomal alterations in human breast cancer

Summary The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1–4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5–8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band-or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10–13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.Presented by Jeffrey M. Trent at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, USA, November 4, 1993; Minisymposium on Molecular Genetics in Breast Cancer.     

Minimal changes with long-term administration of anxiolytics on septal driving of hippocampal rhythmical slow activity

In free-moving male rats, the function relating frequency to the threshold current required to drive hippocampal rhythmical slow activity (RSA; theta) with septal stimulation has a minimum at 7.7 Hz. Classical anxiolytics all increase thresholds in the region of 7.7 Hz, and so does the novel anxiolytic buspirone. However, unlike classical anxiolytics, 2 or 3 weeks are normally required for the onset of the clinical effects of buspirone. This study tested the effects of long-term administration of chlordiazepoxide and buspirone on septal driving of RSA. Separate groups of naive rats received three IP injections per day of chlordiazepoxide (0.4 mg/kg), buspirone (0.1 mg/kg) or saline for 50 days. Both chlordiazepoxide and buspirone increased thresholds at 7.7 Hz, as expected. These acute effects were not significantly changed with chronic administration. Buspirone and chlordiazepoxide produced similar, statistically significant, but small cumulative reductions in thresholds at 6.9 Hz. The present experiments suggest that if the effects of anxiolytic drugs on septally driven RSA provide any basis for their clinical action, then classical anxiolytics may have two actions: an immediate effect on euphoria and tension and a delayed effect on anxiety proper — with buspirone sharing only the latter effect.     

The effect of surgical glove powder on proliferation of human skin fibroblast and monocyte/macrophage

The effect of surgical glove powders (Biosorb, Keoflo, and CaCO3) and Hydrocote (powder-free lubricating agent, Biogel) was examined on human skin fibroblasts and monocyte/macrophage cell lines (U937 and HL-60). Glove powders (0.1-100 micrograms/ml) in the presence of 10% fetal bovine serum (FBS) had no significant effect on the rate of 3H-thymidine uptake and proliferation of these cells after 48 h and 7 days of exposure, respectively. However, they inhibited HL-60 growth after 10 days, and Biosorb and CaCO3 inhibited U937 after 10-21 days of exposure compared with control. In the presence of low serum (0.5%), Biosorb, but not Keoflo, CaCO3, and Hydrocote, inhibited HL-60 cells after the third day of exposure (p < 0.05), whereas they were without any effect on U937 cells. Further incubation resulted in a significant decrease in cell density in all treatments, as well as controls, because of cell death. In the presence of 2% serum, glove powder-treated HL-60 significantly increased in cell numbers during the first 3 days, and the cells became stationary thereafter, whereas Keoflo and CaCO3-stimulated U937 reached a maximal by 9 days of treatment. Coculturing of fibroblasts directly with macrophages (0.4-5 x 10(5) cells per dish) or incubation with macrophage culture-conditioned media (CCM) stimulated quiescent fibroblast growth equal to that induced by 10% and 0.5% serum, respectively (p < 0.05). However, incubation of fibroblasts with glove powder-treated HL-60 CCM (except CaCO3) inhibited (p < 0.05) and CCM from Biosorb-treated U937 stimulated (p < 0.05) fibroblast proliferation. The CCM from glove powder-treated HL-60 and U937 did not have any significant effect on the rate of 3H-thymidine incorporation into fibroblasts compared with controls. The present observations suggest that glove powder action on fibroblast and macrophage growth in vitro depends on both the serum concentration of the culture medium and the length of exposure. The results imply that glove powders may have an adverse effect in vivo by directly influencing the biologic activity of macrophages, as well as other cell types, leading to alterations in the early phases of wound healing.     

Human papillomaviruses and papillomatosis lesions of the female lower genital tract

Objective: The objective of this study was to determine whether human papillomavirus (HPV) infections are involved in the development of papillomatosis lesions of the lower female genital tract.Methods: A total of 616 biopsy specimens of genital papillomatous lesions (307 nodular and 309 papular types) from 598 patients were anaylyzed for the presence of HPV DNA sequences by polymerase chain reaction (PCR). These specimens were also examined by histopathological assessment for characteristic HPV-associated cytological changes, by immunohistochemical staining for HPV-associated antigen, and by electron microscopy for the presence of virions.Results: HPV DNA sequences were found in 97.9% (140 of 143 cases) and 1.1% (1 of 91 cases) of the nodular and papular papillomatosis cases tested, respectively. In 18 patients who had both types of papillomatosis lesions, HPV DNA was invariably found only in nodular tissues. HPV-associated antigen, koilocytosis, and virions were found in 53.6% (98 of 183 cases), 70.5% (129 of 183 cases), and 5.9% (5 of 85 cases) of nodular papillomatosis lesions tested, respectively.Conclusions: These data suggest that nodular papillomatosis was closely associated with HPV infection, but that papular papillomatosis of the lower female genital tract may have an etiology other than HPV infection.     

Combining qualitative with quantitative approaches to study contraceptive pill use

According to large-scale studies, oral contraceptive users become pregnant at rates that exceed ideal use failure rates. It is thought that a major cause is missed pills, but current research on consistent contraceptive pill taking is characterized by inadequate measures and a failure to investigate women's thinking about their own patterns of use. The purpose of this study was to gain some understanding about women's interpretations of consistency in their own pill taking through combining qualitative with quantitative data. The study was conducted in China, where contraception is free and widely available. Five urban and five rural oral contraceptive users were followed for up to three pill-taking cycles during 1996 for a total of 759 person-days. Consistency of pill taking was measured with electronic data obtained from a new blister package made by Anderson Clinical Technologies (Elmhurst, IL). Data from these devices were reviewed and interpreted by the study participants during in-depth private interviews. The users' reasons for missing pills included disruptions in their daily routines, their husband's absence, spotting, and trouble implementing the family planning program's instructions to take one pill per day for 22 days and start the next cycle on the fifth day of menses. One user gave these reasons for two cycles but denied missing numerous pills in her third cycle. Data from a series of four questionnaires showed that most demographic, psychosocial, and service system characteristics were not related to missed pills. However, results suggested that the daily routines of rural living may make consistent use more likely and that instructions for taking the pill may be associated with prolonged pill-free intervals and skipping pills during episodes of spotting. Three of the 10 women were at increased risk of pregnancy during the study period because of their pill-taking pattern. We concluded that the combination of qualitative with quantitative data enhances understanding of contraceptive use. Women themselves offer plausible reasons for their use behaviors. Listening to women could be useful in improving programs.     

Thyroid health status of ammonium perchlorate workers: a cross-sectional occupational health study

Since pharmaceutical exposures to perchlorate are known to suppress thyroid function in patients with hyperthyroidism, a study of employees at a perchlorate manufacturing plant was conducted to assess whether occupational exposure to perchlorate suppresses thyroid function. Exposure to perchlorate was assessed by measurement of ambient air concentrations of total and respirable perchlorate particles, and systemic absorption was assessed by measurement of urinary perchlorate excretion. Airborne exposures ranged from 0.004 to 167 mg total particulate perchlorate per day. Urinary perchlorate measurements demonstrated that exposure to the airborne particulate perchlorate resulted in systemic absorption. Workers were grouped into four exposure categories with mean absorbed perchlorate dosages of 1, 4, 11 and 34 mg perchlorate per day. Thyroid function was assessed by measurement of serum thyroid-stimulating hormone, free thyroxine index, thyroxine, triiodothyronine, thyroid hormone binding ratio, thyroid peroxidase antibodies, and by clinical examination. No differences in thyroid-function parameters were found between the four groups of workers across approximately three orders of magnitude of exposure and of dose. Thus human thyroid function was not affected by these levels of absorbed perchlorate. In addition, no clinical evidence of thyroid abnormalities was found in any exposure group. The blood-cell counts were normal in all groups, indicating no evidence of hematotoxicity in this exposure range. The absence of evidence of an effect on thyroid function or blood cells from occupational airborne perchlorate exposure at a mean absorption of 34 mg/day demonstrates a no-observed-adverse-effect-level (NOAEL) that can assist in the evaluation of human health risks from environmental perchlorate contamination.     

Smoking and the occurrence of Alzheimer's disease: cross-sectional and longitudinal data in a population-based study

The authors tested the hypothesis that smoking exerts a protective effect on Alzheimer's disease or dementia in a population-based cohort of 668 people aged 75-101 years (Sweden). Smoking was negatively associated with prevalent Alzheimer's disease (adjusted odds ratio = 0.6, 95% confidence interval 0.4-1.1) and dementia (adjusted odds ratio = 0.6, 95% confidence interval 0.4-1.0). Over 3-year follow-up (1989-1992), the hazard ratios of incident Alzheimer's disease and dementia due to smoking were 1.1 (95% confidence interval 0.5-2.4) and 1.4 (95% confidence interval 0.8-2.7). Mortality over 5-year follow-up was greater among smokers in demented (hazard ratio = 3.4) than nondemented (hazard ratio = 0.8) subjects. Smoking does not seem protective against Alzheimer's disease or dementia, and the cross-sectional association might be due to differential mortality.