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Biomedical subjects

J Bowen

Publications and source records attributed to J Bowen.

At least 109 records · Page 6Linked to original sources

Cardiovascular disease of connective tissue origin.

Inherited abnormalities of connective tissue elements often cause changes in the structure and function of the cardiovascular system. Well-known heritable disorders of connective tissue in which cardiovascular abnormalities are prominent include the Marfan syndrome and the Ehlers-Danlos syndrome. Connective tissue abnormalities also occur without the associated features of a recognized syndrome. These include isolated valvular prolapse and anuloaortic ectasia. In this review, the cardiovascular features of connective tissue abnormalities--both the recognized syndromes and the isolated abnormalities--are described, important concepts in the diagnosis and treatment of these disorders are reviewed, and the classification of inherited connective tissue abnormalities of the cardiovascular system is discussed.

Cardiovascular Diseases↗

Effects of N-trifluoroacetyladriamycin-14-O-hemiadipate and radiation on L1210 cells.

N-Trifluoroacetyladriamycin-14-O-hemiadipate (AD 143) is the most active among the 14-O-hemiester adriamycin-trifluoroacetamide derivatives and has been selected for preclinical studies. We now report its ability to enhance the kill by ionizing radiation of murine leukemic cells in culture. A 1-h exposure to either 1.28-12.8 micrograms/ml of AD 143 or to 0.16-1.62 micrograms/ml of adriamycin (ADR) was followed at 0 h by graded doses (0-1 Krad) of radiation, and cell viability was assessed by soft agar cloning technique. Regression analyses of the dose-response curve have shown that both compounds, at the concentrations employed, decrease the reciprocal of the slope D0 from 97 rad for radiation alone, to 66-56 rad for AD 143 (1.28-5.12 micrograms/ml) plus radiation, or to 85-61 rad for ADR (0.16-0.65 micrograms/ml) when used with radiation. ADR, however, had a significant "shoulder"-modifying effect. The Dq remained essentially unchanged after AD 143 pretreatment. Quantitation of synergism (superadditivity), additivity, and antagonism was performed by isobologram analysis and by a computerized method based on the "median effect principle." Both approaches have shown that synergism of AD 143 or ADR with radiation becomes apparent with dose escalation. This effect is discernible at significantly lower levels of AD 143 than of ADR, corresponding to less than LD50 measured by the clonogenic assay.

Animals↗

Expression of endogenous murine leukemia virus in transplantable tumor cells and DNA methylation of the viral sequences.

A cell line derived from early passage of a transplantable tumor in athymic mice that initially had been injected with human breast adenocarcinoma cells produced a substantial amount of RNA sequences related to the Kirsten murine leukemia virus. The cell line derived from later passage of transplantation of these tumors diminished viral RNA production. Expression of the viral RNA sequences in these cell lines is inversely correlated with the level of viral DNA methylation in the mouse genome.

Adenocarcinoma↗

Inflammatory breast cancer treated with surgery, chemotherapy and allogeneic tumor cell/BCG immunotherapy.

Thirteen consecutive patients with inflammatory breast cancer were treated with a regimen consisting of cyclic chemotherapy, extended simple mastectomy, and immunotherapy utilizing irradiated allogeneic breast cancer cells admixed with BCG. When surgery was performed after two or more cycles of 5-U, doxorubicin hydrochloride, and cyclophosphamide, there was complete eradication of detectable tumor in three of 11 operative specimens. Two patients had surgery prior to our evaluation and four had prior chemotherapy. Chest wall radiation was initiated after 8-10+ months of chemotherapy at the doxorubicin cardiotoxicity limits. Seven untreated patients, all premenopausal, were compared to our previous series which employed either irradiation after several courses of chemotherapy or irradiation alone. The current series has two relapses (eight months, 25 months) at a median follow-up time of 21 months (range, 8-26 months). In the previous chemoradiotherapy trial, all nine premenopausal patients had relapsed within 25 months, with a median disease free interval of 17 months. In the trial using radiotherapy alone, all ten patients had relapsed by 19 months (median disease free interval, nine months). The present regimen appears to improve control of the disease and further investigation of both surgery and immunotherapy intercalated with cyclic chemotherapy appears warranted in this disease.

Adult↗

Human alpha-1-antichymotrypsin: purification and properties.

Human alpha-1-antichymotrypsin has been purified to homogeneity by the following sequential steps--(a) ammonium sulfate fractionation; (b) chromatography on Cibacron Blue Sepharose at pH 7.0; and (c) chromatography on SP-Sephadex C-50 at pH 5.5. The inhibitor has a molecular weight near 68,000 and contains approximately 26% carbohydrate alpha-1-Antichymotrypsin has an amino-terminal arginine and a carboxy-terminal glycine. It also has some homology with alpha-1-PI based on amino-terminal sequence analysis of both proteins. Complexes of alpha-1-antichymotrypsin with human chymotrypsin and human leukocyte cathepsin G are stable in sodium dodecyl sulfate and have molecular weights near 90,000 suggesting 1:1 complex formation on a molar basis between inhibitor and enzyme.

Amino Acid Sequence↗

Human alpha-1-antichymotrypsin: interaction with chymotrypsin-like proteinases.

The interaction of human plasma alpha-1-antichymotrypsin with serine proteinases from different tissues has been investigated. The protein was found to form stable complexes with pancreatic chymotrypsin, leukocyte cathepsin G, and mast cell chymotrypsin. No inhibition of pancreatic trypsin or leukocyte elastase could be demonstrated. With mixtures containing both alpha-1-antichymotrypsin and alpha-1-proteinase inhibitor, it was found that the former preferentially inactivated leukocyte cathepsin G, while the latter showed a strong preference for pancreatic chymotrypsin. However, leukocyte elastase was specifically inactivated by alpha-1-proteinase inhibitor even in 1:1 mixtures with chymotrypsin. All of these results taken together suggest that one of the primary functions of alpha-1-antichymotrypsin is to inactivate leukocyte cathepsin G, while alpha-1-proteinase inhibitor controls the activity of other serine proteinases, particularly leukocyte elastase.

Binding, Competitive↗

Isolation of albumin from whole human plasma and fractionation of albumin-depleted plasma.

The dye Cibacron Blue F-3-GA was conjugated to Sepharose to provide an affinity column for serum albumin. Passage of whole human plasma through a column of Cibacron Blue-Sepharose results in the removal of approx. 98% of the albumin. The latter can be quantitatively recovered by desorption with NaSCN. Albumin-depleted plasma can be readily resolved into discrete fractions by a combination of conventional biochemical techniques. In particular, the resolution of plasma proteins with properties similar to those of native human plasma albumin can readily be accomplished by ion-exchange chromatography of the Sepharose-dye-treated plasma on DEAE-cellulose.

Ammonium Sulfate↗

Pulmonary water content in critical illness.

Pulmonary extravascular water content was measured using a double indicator technique and results compared with chest radiography. It is concluded that careful chest radiography is an effective and simple technique for assessing the pulmonary extravascular water content.

Body Water↗