Viral hepatitis.
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Biomedical subjects
Publications and source records attributed to A Turner.
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Bryostatin 1 is a macrocyclic lactone protein kinase C (PK-C) activator which has demonstrated promising antileukemic activity in preclinical studies. We have examined the effect of this agent on the metabolism and cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in both log phase and high-density human promyelocytic leukemia cells (HL-60). Exposure of low-density cells to 12.5 nM bryostatin 1 for 24 hr prior to a 4-hr incubation with 1 or 10 microM ara-C resulted in nearly a 2-fold increase in ara-CTP formation. When cells were maintained under high-cell density conditions (e.g. 5 x 10(6) cells/mL) for 24 hr prior to ara-C exposure, a 90% reduction in ara-CTP formation and ara-C DNA incorporation was observed. However, coincubation of high-density cells with bryostatin 1 for 24 hr increased ara-CTP formation 6- to 8-fold, yielding levels essentially equivalent to those achieved in low-density cells. Smaller (but still significant) increases in ara-C DNA incorporation were also noted. Enhancement of ara-CTP formation by bryostatin 1 occurred over a broad ara-C concentration range (0.1 to 100 microM), involved a temperature-dependent process, could not be mimicked by addition of hematopoietic growth factors, and was not related to neutralization of toxic or inhibitory substances in high-density medium. Exposure of cells to bryostatin 1 did not lead to morphologic or functional evidence of HL-60 cell maturation or an increase in cell viability, but did produce a decline in cellular proliferative activity as determined by thymidine and bromodeoxyuridine incorporation and cytofluorometric analysis. Bryostatin 1 did not exert its effects in high-density cells by inhibiting ara-C deamination or by interfering with ara-CTP dephosphorylation, but instead appeared to act by enhancing ara-C phosphorylation. Although cell-free extracts obtained from high-density cells exposed to bryostatin 1 exhibited levels of deoxycytidine kinase activity compared to controls, treated cells did display a significant decline in intracellular dCTP levels (e.g. 0.7 vs 1.3 pmol/10(6)), and nearly a 2-fold increase in ATP and UTP concentrations. Ara-CTP formation was also increased substantially by other PK-C activators including phorbol dibutyrate and mezerein (10-100 nM); this process was inhibited more than 70% by the PK-C inhibitor H-7 (50 microM), but not by the PK-C inhibitors staurosporine, tamoxifen, and HA1004. Finally, coadministration of ara-C and bryostatin 1 resulted in greater than expected inhibitory effects toward HL-60 cell clonogenic growth.(ABSTRACT TRUNCATED AT 400 WORDS)
A 24-year-old West Indian woman with a four-year history of systemic lupus erythematosus presented with progressive dypsnoea due to primary pulmonary hypertension. Despite showing a response to vasodilators, these failed to control the condition. Her pulmonary hypertension increased in severity, eventually resulting in her death. We believe primary pulmonary hypertension to be an unusual complication of systemic lupus erythematosus. We suggest that this diagnosis should be considered in all patients with systemic lupus erythematosus and progressive dypsnoea, as optimum benefit can only be obtained by early institution of vasodilator therapy.
High level tetracycline resistant strains of Neisseria gonorrhoeae (TRNG) have been shown to carry a 40.6 kb (25.2 MDa) conjugative plasmid with a Class M tetracycline resistance determinant. Restriction endonuclease analysis mapping showed that there were at least two different TRNG plasmid types which were found in geographically distinct locations. The physical maps of these two plasmids were compared to a gonococcal conjugative plasmid which did not encode tetracycline resistance. The plasmid type which is endemic in the Netherlands was found to be closely related to the gonococcal conjugative plasmid, which supports the established hypothesis that the 40.6 kb plasmid has evolved by transposition of the TetM determinant into the conjugative plasmid. The plasmid found in the United States has either evolved by substantial divergent evolution or it results from a different transposition event. In the UK there have been isolations of TRNGs carrying either of the two plasmid types reflecting a flow of people both across the Atlantic and in Europe. It is possible that further TetM-containing plasmids will be found in N. gonorrhoeae paralleling the family of TEM beta-lactamase encoding plasmids already described.
During 1989 and 1990 strains of Neisseria gonorrhoeae with reduced susceptibility to ciprofloxacin were isolated in laboratories across the United Kingdom. Treatment failures were associated with some of these infections. These strains were detected by quantitative susceptibility testing because the zone of inhibition around 5 micrograms ciprofloxacin discs shows little decrease in size even with those that are the most resistant. This study determined that strains with reduced susceptibility to ciprofloxacin (MIC of greater than or equal to 0.05 mg/l) produced no zone of inhibition around a commercially available disc containing 30 micrograms of nalidixic acid. Ciprofloxacin sensitive (MIC of less than 0.05 mg/l) strains, however, grew with a large zone (greater than 21 mm) around this disc. These observations suggest that laboratories could adopt this disc test to detect those strains for which ciprofloxacin is not appropriate treatment.
A rapid enzyme activity strip test (Neisstrip, Lab M Ltd, Bury) was compared retrospectively with Phadebact Monoclonal GC coagglutination (Pharmacia Diagnostics, Uppsala, Sweden), cystine trypticase agar sugar utilisation (CTA), and Gonochek II (J W Turner, Liverpool) enzyme methods for identification of 95 Neisseria spp and related species. These had been previously identified using standard methods and included 29 that had given aberrant results. Neisstrip identified correctly all but two, including nine incorrectly identified by Phadebact and 18 erroneously identified using CTA sugars. Results were similar to those obtained with Gonochek II. After this a prospective study was performed testing 400 oxidase positive isolates derived from clinical samples cultured on gonococcal selective medium. Two organisms, both Moraxella spp, were incorrectly identified as N gonorrhoeae by the Neisstrip. The superoxol test, when used with either the Phadebact or Neisstrip tests, maintained 100% sensitivity and specificity. The Neisstrip is a rapid, economic test that is accurate and easy to interpret. It may be used alone or in conjunction with a superoxol test or a coagglutination test, which is relatively accurate but more expensive, and found by some technical staff to be more difficult to interpret.
Wegener's granulomatosis can be a difficult diagnosis to establish. It is not uncommon to require repeated biopsies over many months for histologic confirmation. A recently developed seromarker--anti-neutrophil cytoplasm antibody--ANCA (synonymous with anticytoplasmic autoantibody--ACPA) adds a new and valuable tool for diagnosis. The literature shows this to be a highly specific and sensitive test for Wegener's granulomatosis.
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There is concern that the impaired cell mediated immunity caused by the human immunodeficiency virus may increase the risk of severity of Plasmodium falciparum infection and could lead eventually to a decreased response to standard antimalarial treatment. In 1986, at Mama Yemo Hospital, Kinshasa, Zaire, the incidence of malaria was determined in a cohort of 59 patients who had recently acquired HIV-I infection through blood transfusion and in a cohort of 83 HIV-I seronegative controls who were recipients of HIV-I seronegative blood. All cohort patients were asked to visit the study physician whenever they developed fever. On each of these occasions thick film was examined for the presence of malarial parasites. HIV-I seropositive patients presented more often with episodes of fever per person month observation than HIV-I seronegative patients (P = 0.003). The total number of positive thick films per person months observation was significantly higher among HIV-I seropositive patients than among the HIV-I seronegative ones, but percentages of positive thick films per episode of fever were the same in both groups (46%). During a 5 month period, cohort patients presenting with a moderate attack of malaria were treated with oral quinine 20 mg/kg daily in two doses for 5 days. Twenty-three (92%) of 25 HIV-I seropositive patients and 28 (82%) of 34 HIV-I seronegative patients had a negative film 7 days after starting treatment. This study suggests that there seems to be no direct interaction of major clinical importance between HIV infection and malaria.
In a 2-year study of false-positive anti-HIV-1 tests in blood donors at Manchester and Lancaster Blood Banks, the reactions associated with a HIV-infected cell lysate antigen were compared with those using recombinant-antigen-based tests. In year 1 (cell lysate test) at Manchester BTS 0.21% of 119.178 donations were repeatedly reactive, compared with 0.53% of 119,004 donations in year 2 (recombinant antigen). Reactive sera were tested at Manchester PHL by three different immunoassays. Referred specimens were classified as anti-HIV positive (95-100% reactive in all the assays), equivocal or negative (negative results in all three immunoassays). Two donors were confirmed to be anti-HIV positive over the 2-year period. Most sera were negative by confirmatory immunoassays in years 1 and 2. In year 1, a study of 60 referred sera with sex- and age-matched controls showed high correlation between a reactive anti-HIV-1 screening test and indeterminate anti-HIV-1 patterns on Western blot showing reactions with HIV gag-coded proteins. In year 2, less than 10% of referred sera were reactive by Western blot, and there was no correlation between a reactive screening anti-HIV test, the strength of signal in the test or a reactive Western blot. Follow-up showed that donors whose sera were reactive in years 1 and 2 by the anti-HIV-1 screening test formed almost two different populations. Four donors with equivocal anti-HIV-1 confirmatory tests had anti-HIV 'envelope' reactions.(ABSTRACT TRUNCATED AT 250 WORDS)
A previously fit and well 20 year old man with primary meningococcal arthritis of the left knee is described. Despite intensive search there was no evidence of extra-articular meningococcal infection. He subsequently developed adult respiratory distress syndrome as a rare and previously undescribed complication.
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The molecules involved in the commitment of Xenopus cells to particular germ layers are unknown. The question has been investigated for the cells of the blastula in in vivo cell transplantation assays and in vitro aggregation assays. Using the former technique, we have shown that vegetal cells become committed before gastrulation, even when placed in inappropriate sites. We could find no evidence of regional determination within the endoderm germ layer at the early gastrula stage. In aggregation assays, animal and vegetal cells sorted incompletely at the mid-blastula stage and more efficiently at the gastrula stage. Their behaviour may be mediated by differential expression of adhesion molecules, which so far remain unidentified.
Regional differences in cell recognition properties along the animal-vegetal axis of Xenopus laevis embryos were investigated by using an in vitro cell sorting assay. Dissociated cells were obtained from defined regions of blastula- and early gastrula-stage embryos. Binary combinations of cells from different regions, or from the same region at different ages, were aggregated in stationary culture. Labelling of one population in each pair with a cell-autonomous dye allowed the degree of sorting out in the resulting aggregates to be scored. In combinations of cells from animal caps (prospective ectoderm) and vegetal masses (prospective endoderm), sorting was detectable at the equivalent of late blastula stage and increased with developmental age to the gastrula stage. In addition, cells from the same region but different stages sorted from each other, indicating temporal changes in regional identity. Marginal cells (prospective mesoderm) sorted strongly from vegetal cells but only weakly from animal cells. These results indicate the presence of regional identity in the form of specific recognition properties in cells of the Xenopus blastula. We suggest that these properties act to establish and maintain coherent cell populations, corresponding to the primary germ layers, prior to gastrulation. These results account for the gradual restriction in developmental capacity of blastomeres seen previously in single-cell transplantation experiments from this laboratory.
Melanotic neuroectodermal tumor of childhood is a rare lesion, but its presentation appears to be quite characteristic and a clinical diagnosis may be made with some confidence. Although this is an extremely rapidly growing, aggressive tumor, local excision appears to be adequate for cure.