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Biomedical subjects

K Mitchell

Publications and source records attributed to K Mitchell.

At least 73 records · Page 4Linked to original sources

Molecular genetic analysis of the pyr-4 gene of Neurospora crassa.

By means of S1 nuclease mapping, one transcription origin and three termini are identified for the pyr-4 gene of Neurospora crassa, the same origin being used also by Escherichia coli on the cloned gene. Translation of the clone in mini-cells gives a 50,000 dalton gene product, the same size as that determined for the Neurospora native enzyme. Putative CAAT and TATA boxes, and upstream and downstream potential secondary structures, are identified.

Amino Acid Sequence↗

Identification of three new Ig lambda-like genes in man.

Three new human lambda L chain-like Ig genes are identified by restriction enzyme and nucleotide sequence analysis. Two genes, 14.1 and 16.1, have intact J and C regions, and are potentially functional, with open reading frames. A third gene, 18.1, is a pseudogene. The evolutionary lineage of these genes compared to the known functional locus lambda C1-lambda C6 can be surmised from Southern blot and nucleotide homologies. This study demonstrates that the human lambda gene family is more complex than previously recognized.

Amino Acid Sequence↗

Influence of SLO4 on the leucocyte migration inhibiting factor and on the DTH response.

This phase I study demonstrates the immunostimulating properties of SLO4 administered by the oral route in the healthy volunteer. Responses to the test of DTH (delayed type hypersensitivity) were enhanced by SLO4 and the production of MIF (migration inhibiting factor) involved in this response was stimulated. These properties could be correlated with the previously demonstrated induction of interferon by SLO4.

Adjuvants, Immunologic↗

Macrophage-derived growth factor for osteoblast-like cells and chondrocytes.

Rat resident peritoneal macrophages in primary culture were found to elaborate a mitogenic factor (or factors) for rat osteoblast-like cells and chondrocytes but not for skin fibroblasts. Growth-promoting activity appeared in the incubation medium within the first 20 hr of macrophage culture and was released in amounts that paralleled the number of macrophages per culture. After their proliferative response, as judged by increases in DNA synthesis and cell number, the osteoblast-like cells became enriched in alkaline phosphatase, an index of osteoblast specialization. The macrophage-derived activity was nondialyzable and heat-stable, and it was eliminated by exposure to trypsin. Inhibition of prostaglandin cyclooxygenase failed to modify its generation. Partial purification (Amicon filter concentration, gel filtration) disclosed principal peaks of activity corresponding to Mr of 43,000 and 10,000. The crude conditioned medium and the Mr 43,000-peak, but not the low-molecular-weight peak, exhibited interleukin 1 activity, as judged by the ability to stimulate the proliferation of mouse thymic lymphocytes. The macrophage-derived growth factor described herein may participate in bone remodeling and repair and in primary bone and cartilage growth.

Animals↗

Functional consequence of variation in melanoma antigen expression.

Melanoma cells have been shown to express melanoma-associated antigens and, in many cases, the histocompatibility antigen, HLA-DR. We questioned whether the expression of these antigens was quantitatively altered during the serial passage of melanoma cells in culture. Therefore, we measured the binding of monoclonal antibodies specific for a melanoma-specific antigen and the HLA-DR antigen to melanoma cells from serial passages. Three cell lines were studied. We found that although both the melanoma-associated antigen and the HLA-DR antigen were qualitatively conserved, significant quantitative differences were seen. To study the functional consequences of these differences, we used fluorescence-activated cell sorting to create DR-enriched and DR-depleted populations from a single melanoma cell line heterogeneous for DR expression. We found that the proliferation of allogeneic T cells (measured by the 3H-TdR uptake) cultured with the DR-enriched and -depleted melanoma cell populations was directly related to the amount of the HLA-DR antigen expressed. These results indicate that in performance of experiments using melanoma cell lines quantitative assessment of antigenic expression is important, particularly if the function of a specific antigen is under examination. Further, our data clearly identify the HLA-DR antigen on melanoma cells as a participant in allogeneic lymphocyte stimulation.

Antibodies, Monoclonal↗

Comparison of twice-daily ranitidine and placebo in the treatment of duodenal ulcer--a multicentre study in the United Kingdom.

Treatment of duodenal ulcer with the H2-receptor antagonist ranitidine, 150 mg twice daily has been assessed in a double-blind, placebo controlled study at seven centres in the United Kingdom. One hundred-and-twenty-nine patients entered the trial with endoscopically confirmed duodenal ulcer. Five patients did not comply with the protocol and were excluded from the analysis. Nine patients (1 ranitidine, 8 placebo) did not complete the initial 4 weeks' treatment due to poor symptomatic response; one hundred-and-fifteen (58 ranitidine, 57 placebo) were endoscopically assessed after 4 weeks. The average 4-week healing rate among patients on ranitidine (83%) was significantly greater than that for the placebo group (32%, p less than 0.01). Forty-four patients whose ulcers had not healed received further treatment with ranitidine 150 mg b.d. on an open basis. After a total of up to 8 weeks' active treatment only three patients had not healed. Ulcer symptoms resolved or improved in a greater proportion of patients on ranitidine, and this was associated with a significantly lower antacid consumption. There was no serious unwanted effect associated with ranitidine treatment, and the twice daily dose of 150 mg is apparently a safe and effective short-term treatment for duodenal ulceration.

Adult↗

Prospective comparison of two Sengstaken tubes in the management of patients with variceal haemorrhage.

To compare the efficacy of two oesophageal tamponade tubes, 28 patients with endoscopically proven actively bleeding varices were randomly allocated to be intubated with either a newly available 4-lumen tube incorporating an extra lumen for oesophageal suction, or the modified 3-lumen Sengstaken tube. The patients and the nursing staff preferred using the 4-lumen tube and both aspiration pneumonias and balloon dysfunction occurred less frequently. Variceal haemorrhage was successfully controlled for the first 12 hours in most patients in the two treatment groups, although the incidence of re-bleeding at 48 hours after the tube had been deflated was high.

Adult↗

Colorectal carcinoma antigens detected by hybridoma antibodies.

Hybridoma cells which secrete colorectal carcinoma-specific antibodies have been produced and used to study the antigenic structure of these tumor cells. Nineteen antibodies have been studied in detail, and 15 of these are colorectal carcinoma specific. Only two antibodies reactive with carcinoembryonic antigen (CEA) have been discovered and five other antibodies that react with distinct epitopes on the cell surface have been defined. Several antigens with distinct molecular characteristics have been shown to exist by use of hybridoma antibodies. Six hybridoma antibodies have been shown to mediate antibody-dependent cell-mediated cytotoxicity (ADCC).

Animals↗

Uricosuric response to increasing doses of the indanone diuretic MK-196 in healthy volunteers.

Doses of 20, 40, 60 and 80 mg of the indanone diuretic MK-196 and 40 mg of frusemide were administered in random order to 5 healthy volunteers in a stable metabolic state, on the same day for 5 consecutive weeks. Diuresis, natriuresis and kaluresis increased with increasing doses, the natriuresis lasting for about 12 h and the kaluresis for about 24 h. Uricosuria increased with increasing doses of MK-196 and lasted for about 6 h. The uricosuria was followed by urate retention, so that there was little net change in the renal excretion of urate. Significant weight loss occurred, so that there was probably some associated plasma volume contraction, which would promote urate retention. By contrast, frusemide caused a reduction in renal excretion of urate at all times.

Diuretics↗

Thymic hormone-like restoration by human prealbumin of azathioprine sensitivity of spleen cells from thymectomized mice.

Gel filtration of fresh human serum revealed that over 95% of the thymic-hormone-like activity was present in the fraction representing the total albumin and prealbumin. Further studies demonstrated that the activity resided in the prealbumin fraction; albumin was inactive. Prealbumin was isolated from Cohn fraction IV-1 of pooled human plasma by extraction with aqueous buffer, fractionation with (NH4)2SO4, gel filtration on Sephadex G-150, and preparative disc gel electrophoresis. The final product was homogeneous by analytical gel electrophoresis was 40,000 times more active than the starting material in an azathioprine-sensitive rosette assay. Physical and chemical characterization studies showed that the isolated product was identical to authentic human plasma prealbumin. Isolation of the prealbumin fraction from sera of adult thymectomized mice revealed that the rosette activity was substantially lower than that isolated from sera of normal mice, suggesting a thymic dependence of the prealbumin activity. In vitro and in vivo bioassays of the fraction obtained prior to the final step of the purification procedure support the conclusion that prealbumin exhibits thymic hormone-like activity.

Animals↗

Ciguatera.

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Animals↗