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Biomedical subjects

B Kelly

Publications and source records attributed to B Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1989

Oxygen radicals and antioxidant enzymes alter pulmonary vascular reactivity in the rat lung.

It has been postulated that changes in the availability of partially reduced O2 species, such as O2 radicals, could serve as a link between PO2 in the alveolus and pulmonary vascular tone (Herz 11: 127-141, 1986). To assess this hypothesis, the hemodynamic effects of acute changes in the balance between the production of O2 radicals and availability of antioxidant enzymes were studied in the isolated perfused rat lung. Intravascular generation of O2 radicals, by administration of xanthine-xanthine oxidase, decreased the pulmonary vascular pressor response to alveolar hypoxia (-55 +/- 5%) and angiotensin II (-58 +/- 10%, P less than 0.01 for each) in isolated perfused rat lungs without increasing the lung wet-to-dry weight ratio. Decreases in pulmonary vascular reactivity were inhibited by pretreatment of the lung with desferrioxamine or a mixture of catalase and superoxide dismutase. Catalase and superoxide dismutase preserved the hypoxic pressor response whether given in liposomes or in dissolved form. Superoxide dismutase administered free in solution, or combined with catalase in liposomes, increased the normoxic pulmonary arterial pressure and enhanced vascular reactivity to angiotensin II and hypoxia. Lungs treated with antioxidant enzymes in liposomes had 50% higher lung catalase levels than control lungs (P less than 0.05). These findings demonstrate that exogenous partially reduced O2 species can decrease pulmonary vascular reactivity and suggest that endogenous radicals, superoxide radical in particular, might be important in modulating pulmonary vascular tone.

Animals↗
PubMed1988

Prostaglandins as reducing agents: a model of adenylate cyclase activation?

It has been suggested that adenylate cyclase activation involves reduction of a disulfide linkage. Prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and prostaglandin F2 alpha (PGF2 alpha) were tested for their ability to act as reducing agents with either cytochrome c, or the disulfide 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), the latter with a catalytic amount of ferric chloride. PGE1, PGE2, and PGI2 significantly reduced cytochrome c while PGF2 alpha did not. PGE1, PGE2 and PGI2 reduced DTNB while PGF2 alpha did not. The results are consistent with the postulate that prostaglandins which are effective in activating adenylate cyclase can act as reducing agents and might be involved in reductive activation of adenylate cyclase.

Adenylyl Cyclases↗
PubMed1988

Phosphorylation of tyrosine enhances its electron transfer capability: a model of redox modulation as oncogene expression?

The influence of tyrosine and o-phosphotyrosine on the transfer of electrons to nitrobluetetrazolium (NBT) was studied. Tyrosine phosphate was found to strongly promote the transfer of electrons from ferrous iron to NBT, while tyrosine was inhibitory. The enhancement of NBT reduction by tyrosine phosphate was blocked by superoxide dismutase (SOD). The results suggest a role for phosphorylated tyrosine residues to promote intracellular redox reactions. We suggest that the role of tyrosine protein kinases in cell proliferation and transformation may be to regulate electron transport in as yet undefined cellular systems. Consistent with a unique role for phosphotyrosine, the other commonly occurring phosphoamino acids, o-phosphoserine and o-phosphothreonine were not effective electron transfer agents.

Electron Transport↗
PubMed1987

Preliminary studies on a more effective phototoxic agent than hematoporphyrin.

Phototoxicity of benzoporphyrin derivative (BPD) has been tested in vitro and compared with that of hematoporphyrin (HP). After 1-hour activation with visible light, BPD was 10 times more cytotoxic than HP toward human adherent cell lines: A549 lung cancer, Calu-1 lung carcinoma, and CCD-19Lu normal lung, killing 100% of cells at the concentration of 70 ng/ml. Under the same conditions, BPD was 10-70 times more cytotoxic than HP toward nonadherent cells and cell lines. Tested were human leukemia cell lines HL60, K562, and KG1, normal human lymphocytes, and mouse mastocytoma cell line P815. The concentrations required to kill 100% of cells varied between 10 and 500 ng BPD/ml and between 0.2 and 10 micrograms HP/ml. The difference between the nonadherent cell lines in respect to their sensitivity to phototoxicity of both BPD and HP seemed to be related to the cell sizes, with the smallest cells being the most vulnerable. The most attractive characteristic of BPD in addition to its powerful phototoxicity is its maximum absorption around 700 nm, which is in the range of wavelengths penetrating tissues the best. This characteristic alone could make BPD a drug of choice in cancer photodynamic therapy when the safety of its use is ensured. Preliminary tests in vivo have shown that DBA/2J mice can tolerate a single ip injection of 20-60 micrograms BPD as well as the same dose of HP. The biodistribution and toxicity studies of BPD are under way in our laboratory.

Animals↗
PubMed1987

Safety education in a pediatric primary care setting.

Parents of 171 children coming to the Yale-New Haven Hospital Primary Care Center for their 6-month checkup were randomized into an intervention group (n = 85) and a control group (n = 86). Parents in the intervention group received a three-part individualized course in child safety that required active parental participation. Parts 1, 2, and 3 were given at the 6-month, 9-month, and 12-month well-child visits, respectively. Parents in the control group received routine safety education as provided at well-child visits. The educational phase of the study was completed by 129 families, 65 in the intervention group and 64 in the control group. Safety knowledge, number of hazards in the home, and reported accidents were assessed by a "blinded" community health worker approximately 1 month after the 12-month well-child visit. A total of 109 home visits were made, 55 for the intervention group and 54 for the control group. Parental safety knowledge was assessed based upon pictorial hazard recognition. Of 13 possible hazards, the mean number of hazards recognized by the intervention group parents was 9.4 (n = 55) v 8.4 (n = 50) by the control group parents (t = 2.1, P less than .05, two-tailed). A hazard score was determined for each family based on nine possible hazards observed at the home visit. The mean hazard score for the intervention group was 2.4 (n = 55 v 3.0 (n = 54) for the control group (t = 2.4, P less than .02, two-tailed). Parentally reported accidents and accidents reported in hospital records were similar for both groups. Results of this study suggest that age-appropriate safety education that is repetitive and individualized and that requires active parental participation results in an increase in parental knowledge and an improvement in certain safety practices.

Accident Prevention↗
PubMed1986

Allopurinol can act as an electron transfer agent. Is this relevant during reperfusion injury?

The xanthine oxidase inhibitor allopurinol markedly enhances myocardial function and decreases ventricular irritability during myocardial reperfusion. In the present report, we have evaluated the molecular mechanism of allopurinol action. First, allopurinol was shown to be a weak radical scavenger. Second, allopurinol was found to act as an electron transfer agent from ferrous iron to ferric cytochrome c. The results suggest that the beneficial effect of allopurinol might partially result from its facilitated electron transport during reperfusion when the lipid components of the chain can be expected to be disordered.

Allopurinol↗
PubMed1986

Internalization of transforming growth factor-beta and its receptor in BALB/c 3T3 fibroblasts.

The fate of 125I-labeled transforming growth factor-beta (125I-TGF beta) after binding to its cells surface receptor has been investigated in BALB/c 3T3 mouse fibroblasts. Binding of 125I-TGF beta to cellular receptors at 4 degrees C is pH-sensitive, being markedly decreased at pH less than 6. Most (approximately 90%) of the 125I-TGF beta bound to cells at 4 degrees C can be removed by a brief treatment with acidic medium but is converted into an acid-resistant state rapidly after shifting the cells to 37 degrees C. Cell-bound 125I-TGF beta is degraded at 37 degrees C and the degradation products are released into the medium. The lysosomotropic bases chloroquine, methylamine, and ammonium and the carboxylic ionophore monensin inhibit the degradation and release of 125I-TGF beta from the cells. Cells allowed to accumulate 125I-TGF beta intracellularly by the action of chloroquine or monensin were treated with the bifunctional agent disuccinimidyl suberate in the presence of detergent Triton X-100; this treatment caused the cross-linking of internalized 125I-TGF beta with the 280-kilodalton TGF beta receptor component. Under conditions in which sustained binding and degradation of saturating 125I-TGF beta concentrations occurs, there is no marked decrease in the binding capacity of the cells even when protein synthesis is blocked with cycloheximide. These results indicate that after TGF beta binding the TGF beta:receptor complex becomes rapidly internalized and that TGF beta is directed towards lysosomes where it is degraded and released. However, the cell surface is replenished with TGF beta receptors recycled after internalization or supplied by a large intracellular pool.

Animals↗
PubMed1986

Biologically active precursor for transforming growth factor type alpha, released by retrovirally transformed cells.

Retrovirus-transformed rat cells that actively express transforming growth factor type alpha (TGF-alpha) release into the medium a soluble protein of 17-19 kDa that has been identified as a precursor for TGF-alpha. The identification of this protein as a TGF-alpha precursor is based on its recognition by specific antibodies and by the ability of elastase to convert this protein into a 6-kDa polypeptide with the properties of mature TGF-alpha. This TGF-alpha precursor binds to epidermal growth factor/TGF-alpha receptors and activates the receptor-associated tyrosine kinase activity in intact cells. The biological potency of this precursor is not markedly increased by conversion into mature TGF-alpha in vitro. These studies demonstrate the ability of transformed cells to release a TGF-alpha precursor capable of strong mitogenic action in vivo.

Animals↗
PubMed1985

Stimulation by insulin-like growth factors is required for cellular transformation by type beta transforming growth factor.

Medium conditioned by BRL-3A cells, a known source of insulin-like growth factor II (IGF-II), induced phenotypic transformation (anchorage-independent proliferation) of mouse BALB/c 3T3 fibroblasts but not rat NRK-49F fibroblasts, in the presence of 10% calf serum. A specific radioreceptor assay and a bioassay indicated that BRL-3A conditioned medium contained 0.5-1 ng/ml of type beta transforming growth factor (beta TGF). Purified IGF-II and beta TGF acting together reconstituted the transforming activity of BRL-3A conditioned medium on BALB/c 3T3 cells. Insulin was 5-10% as potent as IGF-II in supporting the transforming action of beta TGF on BALB/c 3T3 cells. NRK-49F cells were phenotypically transformed by beta TGF in the presence of EGF and 10% calf serum as the sole source of IGFs. However, transformation of NRK-49F cells under these conditions was inhibited by addition of purified IGF-binding protein. Addition of an excess of IGF-II prevented the inhibitory action of IGF-binding protein. The different sensitivity of the two cell lines to IGFs was correlated with lower levels of type I IGF receptor and higher levels of type II IGF receptor in NRK-49F cells as compared with BALB/c 3T3 cells. The results suggest that cellular stimulation by IGFs is a prerequisite for transformation of rodent fibroblasts by beta TGF. We propose that transformation of fibroblasts by beta TGF requires concomitant stimulation by the set of growth factors that support normal cell proliferation.

Animals↗
PubMed1979

Isolation and partial characterization of immunologically reactive fractions from chitinase digested cell wall of Trichophyton mentagrophytes.

Cell wall preparations of Trichophyton mentagrophytes were digested with chitinase following which various fractions were isolated by ultrafiltration and Sephadex gel filtration. All fractions isolated contained both polysaccharide and peptide material. A correlation was seen between those fractions capable of eliciting immediate and delayed skin reactions in sensitized guinea pigs and those capable of stimulating the in vitro proliferation of lymphocytes taken from sensitized guinea pigs. These immunologically active fractions also developed precipitin lines with antiserum taken from sensitized animals. A low molecular weight fraction was found to be completely reactive immunologically (UM2(a)), and appeared to have a molecular weight in the range of 2,000--4,000 as assessed by ultrafiltration and gel filtration studies.

Animals↗
PubMed1979

Characterization of immunologically active peptides from the cell wall of T. mentagrophytes.

A low molecular weight fraction from chitinase digested cell walls of T. mentagrophytes containing both polysaccharide and peptide moieties was found to have immunological reactivity at both the cellular and humoral level. This fraction (UM2(a)) was further degraded by treatment with either a combination of pronase and carboxypeptidase A or with trypsin. Peptides were separated from the carbohydrate-rich fraction by ultrafiltration. The carbohydrate-rich fraction retained the ability to induce both immediate and delayed skin reactions in sensitized guinea pigs and to stimulate the proliferation of sensitized lymphocytes in vitro. The peptide moieties retained reactivity in that they caused delayed reactions and lymphocyte proliferation but were unable to induce immediate or Arthus reactions in sensitized animals. Tryptic peptides from UM2(a) were purified by ion exchange chromatography. A high proportion of these peptides demonstrated immunological activity at both the cellular and humoral level since they were capable of inducing delayed reactions and/or lymphocyte transformation, as well as being capable of blocking the complement fixation reaction between UM2(a) and specific antiserum.

Animals↗
PubMed1977

Evidence for a common tumour-associated antigen in extracts of human bronchogenic carcinoma.

Xeno-antiserum specific for antigenic components of bronchogenic carcinoma was raised in rabbits, by passively immunizing them to normal human lung antigens at the same time as immunization with a tumour extract from a squamous-cell carcinoma. Antiserum so raised contained minimal quantities of anti-normal antibody which could be removed by a single absorption with glutaral-dehyde-insolubilized normal lung extract. When tested by quantitative complement fixation with a panel of tumour extracts from surgical specimens, it was found that the antiserum gave positive complement fixation with all squamous-cell carcinoma extracts tested, and with some of the extracts from bronchogenic carcinomas of differing pathological types. The antiserum was essentially negative for pooled extracts from normal lung, liver and spleen but gave a weak positive reaction with an extract of pooled foetal lung tissue.

Antibodies, Neoplasm↗