Biomedical subjects
Publications and source records attributed to D George.
We have utilized in situ hybridization techniques to determine the chromosomal location of alpha-interferon (IFN-alpha) genes in the mouse. The results allow regional assignment of the IFN-alpha gene family to a position close to the center of chromosome 4, in bands C3-C7.
We determined that the coding sequence for a 100-kilodalton super-T antigen found in Simian virus 40 mouse transformants spanned two separate partial repeats of the viral genome. The downstream repeat contained a complete Simian virus 40 large-T-antigen gene, whereas the upstream repeat was a truncated copy of the same gene. When the repeats were separated by subcloning, the capacity to code for the super-T antigen was lost. A small insertion or deletion in the origin-control region which preceded the second repeat could also destroy the ability to code for the 100-kilodalton protein. Our data suggest that differential splicing between parts of two gene copies was responsible for the additional molecular weight of this super-T antigen.
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An asymptomatic boy was found to have coarctation of the thoracic aorta. Despite no history of endocarditis or trauma, a large saccular aneurysm involving the coarctation site was identified angiographically, confirmed, resected surgically, and examined histologically.
We have shown that an alcoholic lotion containing ethyl lactate when applied topically to rat skin under occlusion became localized in the follicles and sebaceous glands. When applied to human facial skin the ethyl lactate was hydrolysed to ethanol and lactic acid, and thereby lowered the skin pH. Under such conditions the growth of recoverable skin bacteria, in particular the anaerobe Propionibacterium acnes, was inhibited, and the hydrolysis of sebum to free fatty acids by lipase derived from the bacteria was greatly impaired. These effects of ethyl lactate would account for its observed clinical efficacy in acne vulgaris.
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Circadian variations of breast surface temperature have been measured in patients with overt or occult benign breast disease, or in those with occult breast cancer. Subjects were studied in a hospital ward environment well-controlled with respect to ambient temperature. Using manual techniques temperatures were recorded half-hourly for 96 hr from replicate sensors placed on quadrants of the left and right breasts inclusive of tumour areas and similar sites on the contralateral breast. Application of time series analysis failed to consistently demonstrate differences in values for the rhythm parameters for the tumour area and contralateral site. It was apparent, however, that the tumour area was generally associated with a reduced initial variance of the series in addition to a reduced percentage variance explained by a time series model with two rhythmic components when compared to the control site. These data suggest that efforts to identify early breast disease from signals of breast temperature should, at least, be directed to studies of temperature variance.
We evaluated the in vitro and in vivo digestibility and clinical tolerance of three corn syrup sugars (DE10, 15, 24) and one infant formula containing corn syrup sugar as the sole carbohydrate source (DE24). In vitro studies were conducted using human duodenal fluid and jejunal mucosa with normal enzyme activities. In vivo studies included intragastric perfusion studies and tolerance tests using the corn syrup sugars and a clinical formula trial in 32 infants with acute diarrhea. Results of the in vitro studies showed that each of the corn syrup sugars was well hydrolyzed by duodenal fluid and by mixtures of duodenal fluids and mucosal homogenates. Similarly, in vivo studies revealed significant hydrolysis in the proximal intestine, as measured during the perfusion studies, and adequate absorption, as indicated by a rise in serum glucose concentration during tolerance tests. Only patients who had a marginal serum glucose rise after a glucose meal had a blunted rise after a corn syrup feeding. More than 85% of the infants beginning the clinical trial tolerated the formula well and gained weight at or above the expected rate for age during the study interval. These data indicate that, except with severe mucosal injury and secondary monosaccharide intolerance, glucose polymers of the dextrose equivalents tested are suitable carbohydrate sources for infants recovering from acute diarrhea.
Complement proteins serve a critical function in the non-antigen-specific elimination of foreign substances and organisms and of immune complexes. Studies of genetic and acquired alterations of complement proteins have provided insights into the pathophysiology of a number of rheumatic diseases, especially those in which immune complexes are believed to have a role in pathogenesis. Complement levels may be helpful in the management of some patients with SLE or vasculitis, and in evaluation of synovial, pleural and pericardial fluids.
The pharmacokinetics and protein binding of sulfapyridine (SP) and its major metabolite, acetylsulfapyridine (ACSP) were examined in 17 prepubertal children and 4 postpubertal adolescents receiving sulfasalazine (SASP) for treatment of inflammatory bowel disease (IBD). Five patients were studied in both active disease and remission. Comparisons were made with a group of 24 outpatients (9-62 years) with IBD controlled on SASP and in remission. Acetylator phenotype was calculated from plasma metabolite ratios. Slow acetylators had increased plasma concentrations of SP and ACSP + SP (P less than 0.05). Apparent SP clearance (clearance/availability) was increased in active disease (P less than 0.05) and AUCSP + ACSP and AUCSP were decreased (P less than 0.05). There were no age-related alterations in apparent SP clearance. Side effects were frequent but were unrelated to SASP dose, SP concentrations, or acetylator phenotype. Disease activity did not significantly alter the serum protein binding of SP or ACSP. The decreased SP and ACSP concentrations seen in active disease may be due to a combination of disease related alterations in either cleavage of SASP or absorption and clearance of SP.
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In a study of the role of oestrogen-receptor analysis in early breast cancer the oestrogen-receptor content of the tumour was estimated in 286 patients undergoing mastectomy. These patients were followed for up to 39 months, and the recurrence of disease was noted in relation to the presence or absence of oestrogen receptor.Recurrence-rates were significantly higher in patients whose tumours did not contain receptors than in those whose tumours did. This same relationship was seen when women with and without axillary metastases were considered separately. The highest rates of recurrence were in women with axillary lymph-node involvement whose tumours lacked oestrogen receptors. Women without axillary-node involvement whose tumours lacked oestrogen receptors showed the same high rate of recurrence as all women with axillary-node involvement. The oestrogen-receptor content of a primary breast cancer appears to be an independent guide to early recurrence of the disease.
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Two cases of primary squamous carcinoma of the breast are described. One of the tumours appeared to have an origin in an epidermoid cyst and had a pseudosarcomatous stroma. The other tumour arose from metaplastic ductal epithelium. A review of the literature is given.
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