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Biomedical subjects

B J Smith

Publications and source records attributed to B J Smith.

At least 217 records · Page 12Linked to original sources
PubMed1987

Stromelysin is an activator of procollagenase. A study with natural and recombinant enzymes.

The latent forms of stromelysin and collagenase from human gingival fibroblasts were purified to homogeneity. These latent proenzymes underwent serial small reductions in Mr upon activation by treatment with either 4-aminophenylmercuric acetate or trypsin. Similar shifts in Mr and activation kinetics were observed upon identical treatments of either recombinant prostromelysin or procollagenase. Prostromelysin showed a lag between activation and Mr fall, suggesting an initial activation by conformational change. Collagenase activity was enhanced up to 12-fold by either natural or recombinant stromelysin in the presence of trypsin or 4-aminophenylmercuric acetate. Stromelysin caused a further apparent decrease in the Mr of procollagenase. Since these important connective-tissue-degrading enzymes are usually co-ordinately produced by cells, a cascade mechanism is proposed in which collagenase is activated by stromelysin.

Collagenases↗
PubMed1987

Limitation of deuterium labelled methoximes as internal standards in the mass spectral analysis of prostaglandins.

A reported method for the preparation of d3-methoxime derivatives as internal standards for prostaglandin assays by gas chromatography-mass spectrometry was evaluated. Sample derivatization resulted in 1.5-86% exchange of the d3-methoxime in a series of prostaglandins. Exchange was minimal when the methoxime was on the 5-membered ring; whereas, acyclic methoximes exhibited extensive exchange. Induced strain energy due to the steric interaction of the hydroxyl group and the C13-C20 alkyl side chain with the gem-dimethoxylamine transition state is offered as an explanation for the unusual stability of PGE2. The use of 18O exchange of the carboxylic acid function is presented as an alternative for the preparation of unavailable labelled eicosanoids.

Deuterium↗
PubMed1987

Concurrent daily cisplatin and radiotherapy in locally advanced squamous carcinoma of the head-and-neck and bronchus.

In order to exploit the cytotoxic and radiosensitising actions of cis-platinum, we have treated 35 patients with locally advanced squamous cell carcinoma of the bronchus or head-and-neck. Each patient underwent radical irradiation (60 Gy/30 fractions over 6 weeks) with daily low-dose intravenous cisplatin (10 mg absolute dose per day) administered within 30 min of each daily radiation fraction. Total dose of cisplatin was 300 mg over 6 weeks. Although treatment was complicated by nausea in almost all patients and transient renal dysfunction in the majority, 27 patients completed treatment and renal function returned to normal or near normal in almost all cases. There was no obvious enhancement of pulmonary or skin toxicity, beyond what would have been expected from treatment with radical radiotherapy alone. There were two treatment-related deaths from renal failure. The response rate was high: all patients achieved at least a partial response, and in head-and-neck sites, there were nine complete responders and seven partial responders. Of the initial 35 patients, of whom all but two had advanced inoperable disease, 11 have died and 21 remain in continuous remission, 8-120 weeks from the start of treatment (median 55 weeks).

Carcinoma, Squamous Cell↗
PubMed1987

Efficacy of intramuscular and intraperitoneal deferoxamine for aluminum chelation.

As intravenous administration of deferoxamine is difficult in home dialysis patients we set out to determine the efficacy of intramuscular (i.m.) and intraperitoneal (i.p.) deferoxamine for removal of aluminum. Patients with serum aluminum levels greater than 90 micrograms/liter were studied in a paired fashion with each patient serving as their own control. Serum and peritoneal fluid aluminum were determined using flameless atomic absorption. In hemodialysis patients 2 g of intravenous deferoxamine increased serum aluminum from 124.7 +/- 32.4 to 415 +/- 192.4 micrograms/liter. One g of deferoxamine given intravenously or intramuscularly resulted in 76.8 +/- 35.3% and 70.4 +/- 23.2%, respectively, of the 2 g i.v. response. The rate at which serum aluminum increased following i.v. deferoxamine infusion was biphasic, with an initial rapid phase lasting 139 minutes followed by a much slower phase. The volume of distribution of aluminum following deferoxamine administration was 12.6 +/- 1.61 and the half life (t1/2) for aluminum removal during hemodialysis was 9.0 +/- 2.0 hours. The increase in serum aluminum following deferoxamine was not due to chelation of erythrocyte aluminum as erythrocyte aluminum remained constant over 24 hours. In patients on continuous ambulatory peritoneal dialysis, 2 g intravenous deferoxamine resulted in the removal of 560 +/- 267 micrograms of aluminum over 24 hours while 2 g deferoxamine given intraperitoneally gave 91 +/- 13% of the intravenous response. Aluminum clearance over 48 hours was twice that for 24 hours for both i.v. and i.p. deferoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1987

Mode of action studies on nitrodiphenyl ether herbicides: I. Use of barley mutants to probe the role of photosynthetic electron transport.

5-[2-Chloro-4-(trifluoromethyl)phenoxy]-2-nitroacetophenone oxime-o-(acetic acid, methyl ester) (DPEI), is a potent nitrodiphenyl ether herbicide which causes rapid leaf wilting, membrane lipid peroxidation, and chlorophyll destruction in a process which is both light- and O(2)-dependent. These effects resemble those of other nitrodiphenyl ether herbicides. Unlike paraquat, the herbicidal effects of DPEI are only slightly reduced by pretreatment with the photosynthetic electron transport inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea. DPEI is a weak inhibitor of photosynthetic electron transport (I(50) 15 micromolar for water to paraquat) in vitro, with at least one site of action at the cytochrome b(6)f complex. Ultrastructural studies and measurements of ethane formation resulting from lipid peroxidation indicate that mutants of barley lacking photosystem I (PSI) (viridis-zb(63)) or photosystem II (viridis-zd(69)) are resistant to paraquat but susceptible to DPEI. The results indicate that electron transfer through both photosystems is not essential for the toxic effects of nitrodiphenyl ether herbicides. Furthermore, the results show that neither cyclic electron transport around PSI, nor the diversion of electrons from PSI to O(2) when NADPH consumption is blocked are essential for the phytotoxicity of nitrodiphenyl ether herbicides.

Journal Article↗
PubMed1986

Comparison of human stromelysin and collagenase by cloning and sequence analysis.

A comparison of the cDNA-derived amino acid sequences of human stromelysin and collagenase with the N-terminal sequences of purified enzymes reveals that these metalloproteinases are highly conserved and that they are secreted as proenzymes. A putative zinc-binding site was identified by its homology with the zinc-chelating sequence of thermolysin. These sequences permitted the identification of: transin, a protein induced in rat fibroblasts either exposed to growth factors or transformed by oncogenic viruses, as the rat homologue of stromelysin, and XHF1, a protein induced in human fibroblasts after treatment with tumourigenic agents, as collagenase.

Amino Acid Sequence↗
PubMed1985

Chromatin proteins share antigenic determinants with neurofilaments.

Antigenic determinants common to distinct proteins may be unambiguously identified by the use of monoclonal antibodies. Some monoclonal antibodies to mammalian neurofilaments have recently been shown to cross-react with the neurofibrillary tangles found at high density in the brains of senile dements with Alzheimers disease (SDAT). Here, we show that these antibodies also cross-react with chromatin proteins, including the linker histones H1 and H1(0). Elevated levels of histone H1(0) have also been reported in SDAT brains.

Alzheimer Disease↗
PubMed1985

Continuous ambulatory peritoneal dialysis and scleroderma.

A patient with scleroderma has been maintained on continuous ambulatory peritoneal dialysis (CAPD) for the past 18 months after having developed associated renal failure. Peritoneal clearances, pulmonary function tests, and hand studies have shown seasonal changes from summer to winter with ambient temperature variations. Rehabilitation and quality of life have been acceptable, blood pressure has been well controlled off all medications, and there has been relatively little disease progression. Attempts have been made to maintain low-dose captopril therapy to suppress plasma renin activity. This case suggests that CAPD is an acceptable and, perhaps, indicated treatment modality for renal failure associated with scleroderma.

Female↗
PubMed1984

On the occurrence of polymers of H1, H1(0) and H5 in extracts of whole tissues. Artificial production during protein preparation.

Inspection of preparations of H1, H1(0) and H5 histones made by extraction of whole tissues has shown that dimers and higher polymers of all three of these proteins are present. They may be formed by the cross-linking action of poly(ADP-ribose) chains which are linked to some of the protein molecules. Putative dimers and higher polymers were noted in preparations from various tissues and species. However, evidence is presented which suggests that production of these polymers is an artifact of precipitation during the preparation of the proteins, so the significance of the polymers is questionable.

Animals↗
PubMed1984

Mapping the binding of monoclonal antibodies to histone H5.

The binding sites of nine monoclonal antibodies along the polypeptide chain of histone H5 were mapped. Immunoblotting experiments with peptides generated from H5 by trypsin digestion, N-bromosuccinimide cleavage, and cyanogen bromide cleavage revealed that all of the monoclonal antibodies reacted with the globular region of H5 which is encompassed by amino acid residues 22-98. Within this globular segment, the epitopes could be subdivided into three regions. Monoclonals 1G11, 2E5, and 2H5 bind to residues 28-31. The close proximity of the epitopes was verified by a competitive enzyme-linked immunosorbent assay and by their binding pattern to a tryptic digest of H5. Monoclonals 4C6, 6E12, and 2E12 bind to a region encompassed by amino acids 28-53 while monoclonals 4H7, 1C3, and 3H9 bind to a region encompassed by residues 53-98. Precise localization of the epitopes in the primary sequence of H5 will allow detailed studies on the mode of binding of H5 to core particles in chromatin.

Animals↗
PubMed1984

A survey of H1o-and H5-like protein structure and distribution in higher and lower eukaryotes.

A survey of H1o and H5-like proteins has been conducted through a range of higher and lower eukaryotic species. All mammals examined possessed H1o proteins, although in variable amounts, and the protein's structure was well conserved, though not invariant. The testis-specific histone Hlt (from rat) did not have an H1o-like structure and it appears that H1o does not occur in spermatocytes in any form. The results also show that Xenopus laevis contains H1o-like proteins, but lower, non-vertebrate eukaryotes (a crustacean, two fungi and a plant tissue) do not possess H1o or H5 proteins. The evidence suggests that H1o and H5 proteins may be considered as belonging to one family, distinct from H1 types. This H1o/H5 family may well be 'replacement histone' variants of H1. The results do not support suggestions of roles such as repression of DNA synthesis or of transcription for H1o/H5 proteins.

Animals↗