GPs and health and safety at work.
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Biomedical subjects
Publications and source records attributed to C Fox.
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A1 adenosine-receptor-antagonist drugs such as 8-cyclopentyl-1,3-dipropylxanthine (CPX) and xanthine amine congener (XAC) are found to activate the efflux of 36Cl- from CFPAC cells. These cells are a pancreatic adenocarcinoma cell line derived from a cystic fibrosis (CF) patient homozygous for the common mutation, deletion of Phe-508. The active concentrations for these compounds are in the low nanomolar range, consistent with action on A1 adenosine receptors. In addition, drug action can be blocked by exogenous agonists such as 2-chloroadenosine and also can be antagonized by removal of endogenous agonists by treatment with adenosine deaminase. Cells lacking the CF genotype and phenotype, such as HT-29 and T84 colon carcinoma cell lines, appear to be resistant to activation of chloride efflux by either drug. CFPAC cells transfected with the CF transmembrane regulator gene, CFTR, are also resistant to activation by CPX. We conclude that, since these antagonists are of relatively low toxicity and appear to act somewhat selectively, they might be considered as promising therapeutic candidates for CF.
The regulation of mucin secretion by SW1116 human colon carcinoma cells has been studied using monoclonal antibody 19-9, which has previously been used to detect mucin in the serum of cancer and cystic fibrosis patients. We found that SW1116 cells constitutively secrete considerable amounts of mucin as the predominant glycoprotein. The secretion of mucin by these cells is independent of cyclic AMP levels, but can be further stimulated by the Ca2+ ionophore A23187. However, arachidonic acid and its metabolites inhibit mucin secretion. Electron microscope studies reveal that the mucin is located near the plasma membrane as well as in vesicular and lysosome-like structures. However, the secretion pathway of mucin is different than that of the lysosomal contents, since arachidonic acid, while inhibiting mucin secretion, actually activates the secretion of the lysosomal enzyme beta-glucuronidase. We suggest that the mechanism of mucin secretion by SW1116 cells occurs by a pathway different from common exocytosis, and possibly by more than one pathway. The response of mucin secretion by SW1116 cells to common secretagogues resembles that of epithelial cells obtained from cystic fibrosis patients. Thus SW1116 cells are an especially interesting system for studying processes related to pathological states associated with excessive constitutive secretion of mucin.
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Virulence of Vibrio vulnificus has been strongly associated with encapsulation and an opaque colony morphology. Capsular polysaccharide was purified from a whole-cell, phosphate-buffered saline-extracted preparation of the opaque, virulent phase of V. vulnificus M06-24 (M06-24/O) by dialysis, centrifugation, enzymatic digestion, and phenol-chloroform extraction. Nuclear magnetic resonance spectroscopic analysis of the purified polysaccharide showed that the polymer was composed of a repeating structure with four sugar residues per repeating subunit: three residues of 2-acetamido-2,6-dideoxyhexopyranose in the alpha-gluco configuration (QuiNAc) and an additional residue of 2-acetamido hexouronate in the alpha-galactopyranose configuration (GalNAcA). The complete carbohydrate structure of the polysaccharide was determined by heteronuclear nuclear magnetic resonance spectroscopy and by high-performance anion-exchange chromatography. The 1H and 13C nuclear magnetic resonance spectra were completely assigned, and vicinal coupling relationships were used to establish the stereochemistry of each sugar residue, its anomeric configuration, and the positions of the glycosidic linkages. The complete structure is: [----3) QuipNAc alpha-(1----3)-GalpNAcA alpha-(1----3)-QuipNAc alpha-(1----]n QuipNAc alpha-(1----4)-increases The polysaccharide was produced by a translucent phase variant of M06-24 (M06-24/T) but not by a translucent, acapsular transposon mutant (CVD752). Antibodies to the polysaccharide were demonstrable in serum from rabbits inoculated with M06-24/O.
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In this study, we have observed that a dissociation may occur in vitro between syncytia formation and HIV spreading. Efficient HIV spreading and virus replication occurred either in HIV-infected LFA-1+ lymphocytes treated with anti-LFA-1 mAb or in HIV-infected lymphocytes genetically deficient in LFA-1, despite the fact that syncytia formation was completely suppressed. Therefore, these results indicate that syncytia formation cannot be used as the sole parameter to evaluate the spread of HIV in vitro.
A 30 year-old man admitted to the hospital two weeks following a motor vehicle accident developed "locked-in" syndrome resulting from traumatic vertebral artery dissection. Aggressive nursing interventions during the acute and early recovery periods were implemented with the hope that both physical and emotional deficits might be alleviated. Although the prognosis for this type of injury is often poor, this patient has improved steadily over a 16-month period.
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A prevalence study of smoking during pregnancy showed that 30% of women in the Jerusalem area were smokers at the beginning of pregnancy and that 67% of women who quit smoking during an earlier pregnancy had started again after delivery. An organized series of health promotion activities for smokers was therefore begun in the framework of routine prenatal care at 4 MCH clinics in Jerusalem. This minimal input smoking cessation program was based on 4 elements: motivation, information, behavioral changes and reinforcement. In face-to-face contact the nurses provided relevant information and recommended specific methods for quitting, based on the reported reasons for smoking. The high prevalence among pregnant women of husbands who had ever smoked suggested their involvement in the program and support to change this harmful behavior. A simple recording system was developed to maintain surveillance of smoking habits and to monitor the planned activities. Controlled evaluation procedures based on the measurement of changes of smoking habits and knowledge and attitudes towards smoking during pregnancy, will test whether this program is feasible for spreading the health promotion message to the family as a whole. Preliminary results point to a positive influence of the intervention population.
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.
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High levels of retrovirus particles are present in the reproductive tract of male mice. In this report epithelial cells that line the lumen of the epididymis are shown to be a principal site of virus synthesis. Aggregates of free virus were evident in the epididymal lumen in addition to the sperm-associated virus previously reported. Large intraluminal cells with characteristics of macrophages and engorged with virus particles were also seen. Virus particles were not detected in testis, liver, brain, or spleen. Thus, the epididymal epithelium is a principal reservoir for retrovirus expression. The virus would be ejaculated as free, cell-associated, and sperm-bound particles. The high level of expression and the relative isolation of epididymal virus from the immune system may relate to venereal transmission of retrovirus infections in mice and humans.
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Computerized nuclear morphometry (CNM) has been compared with the standard histopathologic grading of squamous cell carcinoma in patients who have undergone chemotherapy for head and neck cancers. Statistics were significant between the histopathologic and CNM readings that were done. CNM represents an objective method of quantitating the histopathologic readings of nuclear pheomorphism and cancer differentiation to allow these criteria to be used as prognostic indicators in squamous cancers. CNM readings of individual biopsy specimens from patients were shown to characterize each tumor. This may represent a cytopathologic method for tracking a cancer through whatever course of therapy is given.
The Systolic Hypertension in the Elderly Program (SHEP) Pilot was a collaborative clinical trial that distributed to the clinics all data processing tasks except for randomization assignment codes and morbidity and mortality data. The clinics used customized programs to enter and verify data interactively, to maintain their own local master files, and to transmit the data electronically to the Coordinating Center. We measured quality control based on criteria from centralized as well as distributed models: the error rate for baseline forms was 0.5 per 1000 items. Ninety-eight percent of the forms were query-free, and a central reentry of the data in a 5% sample yielded a miskey rate of 2 per 1000 items. The potential problems of distributed data processing are vulnerability of the local master files and the time demands on Coordinating Center programmers for maintaining clinic computer systems. The advantages are the active involvement of clinic staff in their own quality control, the functional accessibility of the clinics to the Coordinating Center in controlling protocol decisions and data monitoring, and the level of accuracy, completeness, and timeliness of the data that can be achieved.
The pharmacokinetics of ciprofloxacin following a single 100 mg oral dose were evaluated in elderly patients (mean age 74 years), laboratory staff (30-40 years) and students (less than 20 years). There were no significant differences in serum Tmax (1.2-1.3 h) or in overall serum elimination half-life (3.7-4.0 h) but Cmax in elderly patients was more than double that in young volunteers (P less than 0.005). The serum AUC value was greater both in fasting students (1.4 mg/h/l) compared with the same subjects after food (1.09: P less than 0.01) and, after food, in elderly patients (1.95) compared with students (0.81: P less than 0.005). Urinary recoveries were greater in fasting subjects and in all categories of volunteers compared with elderly patients. However, in the elderly, urinary ciprofloxacin concentrations (0-6 h mean 66 mg/l: range 17.4-200 mg/l) were more than adequate for the eradication of urinary pathogens.