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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 703 records · Page 39Linked to original sources

Morphopoietic switch mutations of bacteriophage P2.

During the growth of bacteriophage P4, for which the genome of bacteriophage P2 is needed as helper, the decision whether to make large, P2 size, heads or small, P4 size, heads depends on the size-directing function of P4's sid gene and on P2's "sid responsiveness." P2 mutants (=P2 sir) impaired in their response to P4's sid function are readily obtainable as one class of P2 plaque formers selected on certain P4 cl plasmid lysogens. We describe nine P2 sir mutants of independent origin. For eight we could assign their sir mutation to P2 gene N, which encodes the major capsid protein. DNA sequencing indicated an open reading frame of 357 codons for gene N and showed these sir mutations to affect only four codons within a 38-codon segment in the middle of N. Seven mutations are missense mutations (three of them identical); one is a deletion of one codon. There seems to be a correlation between the phenotypic "strength" of the sir mutations and the type of amino acid replacement by missense mutations. Although the weakest mutation, sir7, could not yet be assigned to any P2 gene, it appears clear from this work that P2's N gene product is the major (or only) target of P4's Sid gene function.

Amino Acid Sequence↗

Retroviral arthritis: phenotypic analysis of cells in the synovial fluid of sheep with inflammatory synovitis associated with visna virus infection.

A phenotypic analysis on synovial fluid cells from the carpal and tarsal joints of sheep with visna virus-induced inflammatory synovitis was performed. The results showed increased representation of cells bearing lymphocyte, macrophage, and dendritic cell markers compared to equivalent synovial fluid cells from normal uninfected age-matched controls. In infected sheep, CD8+ T cells tended to predominate over CD4+ cells, while the numbers of gamma delta T cells varied from being absent in some samples to constituting the major T cell subset in others. B cells were found in relatively smaller numbers. Analysis of the large mononuclear cells showed that they stained with monoclonal antibodies that recognize macrophages and afferent lymph dendritic cells. Major histocompatibility complex (MHC) class II+ macrophage/dendritic cells were found in normal joints, but significantly elevated proportions of such cells were present in the carpal joints of infected sheep. The intensity of MHC class II staining was also significantly elevated in infected animals compared to control animals. A high proportion of these cells also stained for CD1 in both normal and infected animals, but were significantly elevated in number in the carpal joints of infected sheep. The elevated proportion of cells expressing molecules associated with accessary cell function and the increase in the numbers of accessory molecules per cell suggests an enhanced capacity for presenting antigen to a variety of T cell subsets within the joints of infected sheep, which could initiate or perpetuate potentially damaging local synovial inflammatory responses.

Animals↗

Codeine: developmental toxicity in hamsters and mice.

Timed-pregnant LVG Syrian hamsters and Swiss CD-1 mice were dosed orally twice daily (b.i.d.) with codeine in water on Gestational Days (gd) 5-13 (0, 10, 50, or 150 mg/kg, b.i.d.--hamsters) or 6-15 (0, 37.5, 75, 150, or 300 mg/kg, b.i.d.--mice). Dams were necropsied on gd 14 (hamsters) or 17 (mice), and fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations. No maternal deaths were observed in hamsters, while 19% of the pregnant mice in the high-dose group died. Maternal weight gain (gestational and treatment periods) and gravid uterine weights were significantly depressed in hamsters (150 mg/kg, b.i.d.) and in mice (300 mg/kg, b.i.d.). However, the corrected weight gain for both species, although decreased, was not significantly different from that of the controls. In both species, maternal liver weights (relative) were significantly increased in the high-dose groups. There were increases in the percentage resorptions per pregnant dam and in the proportion of litters with 100% resorptions in the high-dose groups of both species. Considering only live litters, the number of live fetuses per litter and the sex ratio were unaffected in both species. Mean fetal body weights were also significantly decreased in the 50 and 150 mg/kg, b.i.d. (hamsters), and the 150 and 300 mg/kg, b.i.d. (mice), groups. The no-observed-adverse-effect levels (NOAELs) for developmental toxicity were 10 (hamsters) and 75 (mice) mg/kg, b.i.d., whereas the NOAELs for maternal toxicity were 50 (hamsters) and 150 (mice) mg/kg, b.i.d. The predominant structural malformation in hamsters was meningoencephalocele (high-dose group only), affecting 3% of fetuses and 19% of litters (neither statistically significant). Codeine did not induce any increase in structural malformations in mice. Thus, codeine produced developmental toxicity (as indicated by decreased fetal body weight) at doses below those producing maternal toxicity in both hamsters and mice. In the hamster, the more sensitive species to codeine developmental toxicity, effects were observed at a total daily dose of 100 mg/kg, which is only 11 times the maximum human therapeutic oral dose.

Abnormalities, Drug-Induced↗

The effects of ethylene dibromide on semen quality and fertility in the rabbit: evaluation of a model for human seminal characteristics.

Mature (12 months old) male New Zealand White rabbits (8-10/group) were dosed subcutaneously with ethylene dibromide (EDB) in corn oil (untreated and vehicle controls, 15, 30, or 45 mg/kg body wt/day for 5 days). Weekly semen samples (for 6 weeks preexposure, during treatment, and 12 weeks postdosing [pd]) were analyzed for sperm concentration, number, morphology, viability, and motion parameters (velocity, linearity, beat cross-frequency, amplitude of lateral head displacement (ALH), and circularity), and semen pH, osmolality, volume, fructose, citric acid, carnitine, protein, and acid phosphatase (AP). Male fertility was assessed preexposure and at 4 and 12 weeks pd by artificial insemination of three females/male/time point with one million motile sperm. The percentage pregnant females, litter size, fetal body weights, and structural development were assessed. In the 45 mg/kg dose group of males there was 30% mortality and liver damage in 43% of the survivors as evidenced by increased levels of serum enzymes. Also in this group, EDB produced significant decreases in sperm velocity, percentage motility, and ALH (up to 25% at various times pd). There were also dose-related decreases in semen pH (up to 2%) and total ejaculate volume (up to 23%, 15 and 30 mg/kg dose groups only). AP activities were significantly elevated (up to 116%) 2 weeks pd in the 45 mg/kg dose group. All other semen parameters evaluated were unaffected. Male fertility and fetal structural development were also unaffected. Of the seven semen parameters perturbed by EDB in humans (Schrader et al., 1988), four were also affected in the rabbit (sperm velocity, percentage motility, pH, and volume), whereas sperm number, viability, and morphology were not. Thus, some of the male reproductive effects of EDB in the human have been modelled in the rabbit, although the rabbit appears not to be as sensitive, since semen parameters were affected only at doses close to the LD50 (55 mg/kg). The present study (together with other published data) suggests that the rabbit appears to be a potential model for male reproductive toxicity in humans, warranting further evaluation.

Acid Phosphatase↗

Socioeconomic status and cancer mortality and incidence in Melbourne.

Data were obtained for all deaths registered between 1979-1983, and for all new cancers recorded at the Victorian Cancer Registry between 1982-1983, in residents of Melbourne. A socioeconomic status (SES) measure had been produced for each local government area (LGA) by principal components analysis of sociodemographic variables recorded at the 1981 census. A SES score from 1 to 10 was assigned to each death and cancer. Population data from the census were similarly scored. Age standardised rates for all cause mortality, for mortality from all causes other than cancer and for both incidence and mortality of total cancers, cancer of the stomach, colon, rectum, lung, female breast, cervix, uterus, prostate and bladder, and for melanoma, lymphoma and leukaemia were analysed as a function of SES decile using weighted linear regression. Despite the limited number of years of data and the misclassification of the SES score, analyses showed there were inequitable distributions of mortality, and of some major cancers, across social strata in Melbourne during the early 1980s. The incidences of cancer of the breast, colon, prostate and melanoma were all positively associated with SES, while the incidences of cancer of the stomach, lung and cervix demonstrated negative SES gradients. For cancers where incidence showed a significant SES gradient there was a similar SES gradient with mortality. These patterns are consistent with the literature and implicate SES differences in education and access to services. Implications for health policy are discussed.

Adult↗

Liver function tests and neuropsychologic impairment in substance abusers.

The relationship between residual neuropsychologic dysfunction in alcoholics and subtle changes in liver function during acute phases of treatment was examined. Noncirrhotic alcoholics who exhibited extreme elevations in the liver enzyme gamma-glutamyl transferase (GGT) were found to have greater impairments in tasks of visuoperceptual and conceptual abilities when compared to alcoholics with normal or only mild elevations in GGT. The relationship between acute liver dysfunction and residual neuropsychologic impairment appeared to be independent of age and patterns of drinking. The implications of these findings in relation to treatment planning and prognosis of alcoholics are discussed.

Adult↗

Vaginal cyclicity, sexual receptivity, and eating behavior of the female rat following treatment with chlordecone.

The effects of 25, 50, or 75 mg/kg chlordecone on vaginal and behavioral estrus were examined following treatment of intact rats during estrus, diestrus 1, or diestrus 2. Chlordecone accelerated vaginal estrus, but sexual behavior was eliminated, delayed, or reduced. Chlordecone treatment led to the presence of vaginal estrus within 2 days, but reduced or eliminated sexual behavior on the evening of predicted proestrus. Of the females that received chlordecone, 20% to 50% showed some behavior on the day after the evening of predicted proestrus and 20% to 35% never showed behavior during the 8-day observation period. Although the lordosis to mount ratio was still reduced, the occurrence of behavior a day late suggested that the pesticide had delayed behavioral estrus. Chlordecone also rapidly suppressed food intake and led to a significant decline in body weight; these nutritional factors could have contributed to the disrupted estrous cycle. Some support for this possibility was derived from a reduced sexual receptivity on the evening of proestrus when the caloric intake of untreated female rats was matched to that of the chlordecone treated animals. However, the effects of caloric reduction on proestrous lordosis behavior were less robust than seen following chlordecone. Chlordecone treatment on diestrus 2 reduced the number of progesterone receptors in uterine tissue of females on the predicted day of proestrus. This suggested that the tissue sensitivity to circulating levels of progesterone would be reduced within 2 days after chlordecone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biliary strictures in hepatic transplantation.

Between August 1985 and December 1990, 198 liver transplantations were performed. Among 18 patients, 20 biliary strictures were identified, which were categorized as anastomotic (n = 6), nonanastomotic central hilar (n = 8), and nonanastomotic peripheral (n = 6). Pretransplant disease, hepatic artery patency, presence of acute or chronic rejection, and donor cold ischemia times were tabulated for each case. Among the six patients with peripheral strictures, three had sclerosing cholangitis prior to transplantation. Three patients with nonanastomotic strictures experienced chronic rejection. The mean cold ischemia time for patients with nonanastomotic strictures was 9.75 hours versus 8.1 hours for nonstrictured transplants (P = .025). Balloon dilation was performed in 13 patients; follow-up longer than 6 months was available for nine patients. Dilation was successful in four cases. Among the five failures, only one patient has needed surgery. An association was noted between nonanastomotic biliary strictures and prolonged donor cold ischemia time, between peripheral nonanastomotic strictures and pretransplant sclerosing cholangitis, and between nonanastomotic strictures and chronic rejection. Percutaneous balloon dilation was found useful in the treatment of the strictured transplant.

Biliary Tract Diseases↗

Impact of a student interdisciplinary oncology team project.

Team approaches to health care have been developing steadily over the past 30 years in response to increasing concerns about accessibility, efficiency, and comprehensiveness of health care services. Implementation of team approaches has been accompanied by development of curricula and educational experiences that educate health professionals both in effective teamwork skills and in understanding the contributions each profession makes to comprehensive health care. Such a project was implemented in 1975 at the University of Hawaii involving the Schools of Nursing, Social Work, and Medicine. This paper describes an evaluation of the impact of an interdisciplinary team approach to the care of oncology patients by students in medicine, nursing, and social work. Evaluation is based upon project objectives using a series of pre- and posttest measures and weekly logs by participating students between 1979 and 1985. The paper addresses the following questions: What was the impact of the team experience on participating students as reflected in evaluation data? How effective was the Student Interdisciplinary Oncology Team Project in helping students achieve each of the seven stated objectives? What are the differences in professional socialization processes among the three professions represented in the project?

Education, Medical, Undergraduate↗

Epidemiological evidence for the 'two-disease hypothesis' in Hodgkin's disease.

This study relates to 1803 newly diagnosed cases of Hodgkin's Disease (HD) registered between 1984 and 1988 by a specialist leukaemia-lymphoma registry covering approximately half of England and Wales. In addition to registration data the analyses use routine census data. Rye classification is available for the majority of cases with only 7% being unclassified. The data confirm that the young adult peak in HD occurrence is attributable to the nodular sclerosing subtype (NS), and there is some evidence that NS has a different geographical distribution by county to the other Rye subtypes. Because of possible geographical biases in the classification, subsequent spatial analyses are disaggregated by age at diagnosis with particular emphasis being placed on the two age groups 0-34 and 50-79 years. For these, trends of risk by areal socioeconomic status are in opposite directions and the effects of urban-rural status while in the same direction also differ significantly. Allowance for these does not, however, explain the significant difference between the county distributions of the two groups. Patterns of spatial clustering are quite distinct with evidence for local spatial aggregation amongst younger cases.

Adolescent↗

A comparison of memory and attention in Turner syndrome and learning disability.

Compared short-term verbal memory, sustained attention, and impulsivity in 13 children with Turner syndrome to 13 females and 14 males with learning disability who had neuropsychological patterns similar to the children with Turner syndrome. Similar patterns of short-term memory deficits were found in all three groups. There were no significant differences among the groups on computer measures of sustained attention and impulsivity. However, extreme variability of the attention and impulsivity scores for the Turner syndrome group may reflect atypical attention deficit disorder in some of these children.

Attention↗

High definition computed tomography in rheumatoid arthritis associated pulmonary disease.

Eighteen patients with rheumatoid arthritis (American Rheumatism Association definition) were selected consecutively from a rheumatology clinic. All patients were examined with plain chest radiographs, thin slice computed tomography, and pulmonary function tests. Four patients with normal chest radiographs, and normal pulmonary function tests were found to have normal CT scans. In ten patients, abnormalities consistent with rheumatoid associated lung disease were demonstrated, including changes of interstitial fibrosis in seven cases. This fibrosis had a predominantly peripheral pattern on CT scan. Computed tomography was found to be more sensitive than plain radiographs in detecting abnormalities; however, all the patients in this series with CT lung changes had abnormalities on pulmonary function testing.

Adult↗

Chronic lymphocytic leukemia with coexistent Hodgkin's disease. Implications for the origin of the Reed-Sternberg cell.

The association of chronic lymphocytic leukemia (CLL) and Hodgkin's disease has been controversial. Pleomorphic lymphoreticular cells resembling Reed-Sternberg cells have been observed in Richter's syndrome. Although most observers have favored the view that these cells are a component of a pleomorphic non-Hodgkin's lymphoma, some cases of histologically typical Hodgkin's disease have been described. We have studied two cases that appear to represent composite CLL and Hodgkin's disease, providing evidence for an interrelationship of these two disorders. Classic Reed-Sternberg cells and variants (RS-H) were seen in a background that was otherwise typical of CLL. Both patients initially presented with characteristic findings of CLL in the peripheral blood and bone marrow. The first patient was found to have RS-H cells within lymph nodes at initial presentation, and ultimately progressed to develop a disseminated lymphoma characteristic of Hodgkin's disease. In the second patient, RS-H cells were not discovered until 5 years later. Immunophenotypic studies confirmed these morphologic impressions. The predominant lymphocyte population had a phenotype consistent with B-cell CLL. By contrast, the RS-H cells were strongly positive for CD15 (Leu M1) with staining of the Golgi region and cell membrane. Additionally, the RS-H cells were surrounded by rosettes of lymphocytes that marked as T cells. In both of the patients, a small percentage of RS-H cells expressed positivity for the B-cell marker L-26, which may indicate an origin from the underlying CLL. These findings support a B-cell origin for the malignant cell in some cases of Hodgkin's disease and suggest that Hodgkin's disease in some patients may be related to or derived from a coexisting lymphoid malignancy.

Antigens, Differentiation↗

Determination of vigabatrin in plasma by reversed-phase high-performance liquid chromatography.

A method is described for the determination of vigabatrin in 50 microliters of plasma by isocratic high-performance liquid chromatography using fluorescence detection. The procedure involves protein precipitation with methanol followed by precolumn derivatisation with o-phthaldialdehyde reagent. Separation of the derivatised vigabatrin was achieved on a Microsorb C18 column using a mobile phase of 10 mM orthophosphoric acid:acetonitrile:methanol (6:3:1) at a flow rate of 2.0 ml/min. Assay time is 15 min and chromatograms show no interference from commonly coadministered anticonvulsant drugs. The total analytical error within the range of 0.85-85 micrograms/ml was found to be 7.6% with the within-replicates error of 2.76%. The minimum detection limit was 0.08 micrograms/ml and the minimum quantitation limit was 0.54 micrograms/ml.

Aminocaproates↗

Suppression of graft-versus-host reaction in severe combined immunodeficiency with maternal-fetal T cell engraftment.

Simultaneous engraftment of maternal T cells and T cells from unrelated transfusion donor in an infant with severe combined immunodeficiency disease (SCID) was identified by HLA typing blood lymphocytes of the patient, her triplet siblings, parents, and the platelet donor from whom the patient received nonirradiated platelet transfusion. T cell grafts from both the mother and platelet donor were stable for several months, but the graft-versus-host reactions (GvHR) remained mild and immune function was deficient. We hypothesize that immunosuppressive effects of a maternal-fetal GvHR may have modified the expected lethal GvHR from platelet donor's T cells.

Agammaglobulinemia↗

Unexpected localisation of cells expressing a prespore marker of Dictyostelium discoideum.

We show that the anterior, prestalk region of the Dictyostelium slug contains cells which express, or have expressed, a prespore-specific marker. We term these cells "prespore-like cells" (PLC). In newly formed slugs there is a sharp prespore/prestalk boundary, with very few PLC, but after several days of migration the clear demarcation between prespore and prestalk zones breaks down because the number of PLC increases dramatically. This is consistent with previous observations showing there to be rapid interchange of cells between the prestalk and prespore regions. This is not, however, their only source, as a scattering of PLC appear when separate prestalk and prespore regions first become apparent at the time of tip formation. Also, at culmination, there is respecification of "prespore" cells at the prestalk/prespore boundary to form part of the mature stalk. The existence of these cells, and of PLC, may explain why we find prespore-specific mRNAs in mature stalk cells.

Blotting, Northern↗