Biomedical subjects
Publications and source records attributed to A Davidson.
A case of zygomycosis due to Rhizopus microsporus variety microsporus in a patient who was receiving haemodialysis is described. This infection resulted in amputation of the right hand. Criteria to identify the fungus are presented. The pathogenesis and treatment of zygomycosis are discussed.
The one-cell mouse embryo system has previously been shown to be more sensitive than the two-cell system to mild changes in in vitro fertilization (IVF) culture media. To determine whether this greater sensitivity is related to the developmental stage or to the length of exposure, one-cell embryos were collected and cultured in control media (Ham's F-10, 282 mOsm/liter), in media of altered osmolality (260, 300, and 316 mOsm/liter), or in media containing Cidex diluted 1:100,000. The one-cell embryos were exposed to control or altered media in four patterns: control group--control medium for 96 hr; Group A--altered medium for the first 24 hr followed by control medium for 72 hr; Group B--control medium for the first 24 hr followed by altered medium for 72 hr; and Group C--control medium for the first 24 hr, altered medium for the next 24 hr, and control medium again for 48 hr. The percentage of embryos developing to blastocysts in Group A (exposed to adverse conditions only for the first 24 hr of culture) was significantly lower than in the control group under all conditions studied. In contrast, the percentage of blastocysts developing in Group B was significantly lower than in the control group only in medium of 315 mOsm/liter and was not different from that in controls under the other conditions studied. There was no difference between Group C and the control group. We conclude that the higher sensitivity of the one-cell system is an inherent property of the one-cell stage, as exposure of the embryo during this critical first 24-hr period proved to have the most profound consequences.
Female mice were superovulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) and mated with male mice. One-cell (n = 429) and 2-cell (n = 450) embryos were collected 20 and 42 hours after hCG and cultured in Ham's F-10 medium (Gibco, Grand Island, NY) (282 mOsm/l, pH 7.4) and in media of altered osmolality (260, 300, 316 mOsm/l), altered pH (7.0, 7.8, 8.0) or various dilutions of Cidex (Surgikos, Arlington, TX) (1:1000, 1:10,000, 1:100,000). Stages of development were observed for 4 days. The development of embryos in the 1-cell system was significantly impaired under all studied conditions by the 4-cell stage of development. The 2-cell system failed to detect trace amounts of Cidex in the culture media and an increase in osmolality to 300 mOsm/l. Other changes in osmolality (260 mOsm/l) and pH (7.8) were detected by the 2-cell system only at the blastocyst stage. The authors conclude that the 1-cell system is more sensitive than the 2-cell system to mild changes in in vitro fertilization culture media.
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The anti-idiotype 3I which recognizes a determinant on kappa-chains of anti-DNA antibodies in SLE patients also recognizes a determinant on kappa-chains of 82/706 myeloma proteins tested. Twenty-nine of these 82 proteins bind to double-stranded DNA, including two monoclonal IgM, one monoclonal IgA, and 26 monoclonal IgG proteins. DNA binding is much more frequent in the IgG than in the IgM myeloma proteins (p less than 0.001), and is also associated with cationic antibody charge. Two-dimensional gel electrophoresis reveals markedly increased charge heterogeneity of both heavy and light chains of the monoclonal IgG as compared with the monoclonal IgM proteins. We postulate that the increased charge heterogeneity of the IgG-associated 3I-reactive kappa-light chains may reflect somatic mutation, and that DNA specificity within the 3I idiotype system arises by somatic mutation of germ-line genes found in normal individuals. DNA binding may be associated with those mutations that give rise to a cationic immunoglobulin charge.
Nu1 and A, the genes coding for bacteriophage lambda DNA terminase, rank among the most poorly translated genes expressed in E. coli. To understand the reason for this low level of translation the genes were cloned into plasmids and their expression measured. In addition, the wild type DNA sequences immediately preceding the genes were reduced and modified. It was found that the elements that control translation are contained in the 100 base pairs upstream from the initiation codon. Interchanging these upstream sequences with those of an efficiently translated gene dramatically increased the translation of terminase subunits. It seems unlikely that the rare codons present in the genes, and any feature of their mRNA secondary structure play a role in the control of their translation. The elimination of cos from plasmids containing Nu1 and A also resulted in an increase in terminase production. This result suggests a role for cos in the control of late gene expression. The terminase subunit overproducer strains are potentially very useful for the design of improved DNA packaging and cosmid mapping techniques.
Familial polyposis coli is a disease state that offers an opportunity to obtain colon tissue in a predictable manner in terms of identifying putative premalignant markers. Our results support the hypothesis that a sequential series of alterations occur in the dynamics of glycoprotein metabolism as normal colonic mucosa progresses to colon adenocarcinoma. Specifically, both nonmalignant polyps and colon adenocarcinoma tissue expressed diminished glycosylation of proteins, whereas an elevated level of activity for membrane-associated glycosyltransferases does not appear until colon cancer itself develops.
A new in vitro bacteriophage lambda DNA packaging system is described in which all the proteins necessary for head morphogenesis are supplied by extracts of plasmid-transformed cells. This assay is used to demonstrate that the lambda FI gene product (gpFI) is necessary for maximal packaging efficiency when proheads and terminase are present in limiting amounts. A 100- to 200-fold decrease in packaging is seen when gpFI is omitted. gpFI is shown to act at and/or after the stage in packaging where proheads bind to the DNA:terminase complex.
To elucidate further the clinical significance of the anticentromere antibody (ACA), 32 Australian-born Caucasian patients with scleroderma (SD) or CREST (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia) were reclassified as ACA-positive (19 patients) or ACA-negative (13 patients). The clinical features of the two groups were compared. Mean disease duration was 11.7 years for the ACA-positive group and 1.1 years for the ACA-negative group. No ACA-positive patient had generalized skin SD, whereas all ACA-negative patients with disease duration greater than 6 months had moderate or severe proximal scleroderma. Only one ACA-positive patient had serious extra-oesophageal internal organ involvement, excluding primary biliary cirrhosis (three patients) which is itself associated with ACA. Three ACA-negative patients had serious extra-oesophageal internal organ involvement. No ACA-positive patient had been treated with penicillamine or captopril compared with 11 ACA-negative patients. Thus ACA appears to be a favourable prognostic indicator. Analysis of individual CREST manifestations in ACA-positive patients revealed that most had 'incomplete CREST', lacking one or two of the five features. The classification of SD patients as ACA-positive or ACA-negative is suggested.
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Hydroxocobalamin (HOCb) when mixed with sodium nitroprusside (SNP) in a 10:1 or 1:1 molar ratio had no significant effect on the relaxation of noradrenaline-precontracted rat aortic rings. However, the addition of HOCb did prolong the time taken for the relaxant response to occur. The time taken for a 0.34 microM SNP dose to exert 50% of its relaxant effect was increased by about 120 and 35% with 10:1 and 1:1 HOCb/SNP molar ratio mixtures, respectively. A 0.5:1 HOCb/SNP molar ratio mixture caused no prolongation. In incubations with [14C]SNP, it was found that mixing with equimolar, or greater, amounts of HOCb, reduced aortic tissue uptake of radioactivity. The results support the hypothesis that both SNP alone and SNP/HOCb complexes breakdown extracellularly to release the same amount of active species, but that in the case of the complexes the active agent is released at a slower rate.
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