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Biomedical subjects

A R Jones

Publications and source records attributed to A R Jones.

At least 91 records · Page 5Linked to original sources
PubMed1989

Oxidative metabolic activity of boar spermatozoa: a system for assessing anti-glycolytic activity of potential inhibitors in vitro.

The oxidative metabolic capability of mature boar spermatozoa has been determined in vitro. The high rate of oxidation of fructose, glucose, glycerol, glycerol-3-phosphate and lactate to CO2 and the optimization of incubation conditions indicates that these cells could constitute a model system for investigating the anti-glycolytic activity of potential male anti-fertility agents. The effects of several chemical agents on the oxidative metabolism of boar spermatozoa are reported.

Acetone↗
PubMed1989

Hemopoietic origin of factor XIII A subunits in platelets, monocytes, and plasma. Evidence from bone marrow transplantation studies.

Factor XIII A subunit (FXIIIA) is found in plasma, platelets, and monocytes. The hemopoietic contributions to FXIIIA in these components were studied in patients transplanted with marrows from donors with different FXIIIA phenotypes. In three patients with successful engraftment (by DNA genotyping, red cell phenotyping, and cytogenetic studies) platelet and monocyte FXIIIA changed to donor phenotypes with hematologic recovery. Thus, FXIIIA in platelets and monocytes is synthesized de novo and/or from their progenitor cells. Plasma FXIIIA phenotype change after transplantation was more complex. Patient I changed from phenotype 1-1 (one electrophoretically fast band) to 1-2 (three bands) in 115 d; patients 2 and 3 did not change completely from phenotype 1-2 to 1-1 in up to 458 d, but did show enrichment of the fastest band. Thus, while there is a definite contribution of donor hemopoiesis to plasma FXIIIA, another source of recipient FXIIIA appears to be present to delay or prevent the phenotype change.

Adult↗
PubMed1989

Treatment of advanced Hodgkin's disease with high dose melphalan and autologous bone marrow transplantation.

Twenty patients with Hodgkin's disease which had relapsed at least once after chemotherapy, were treated with melphalan 140-220 mg/m2 i.v. followed by reinfusion of non-cryopreserved autologous bone marrow. Four patients (20%) remain alive and disease-free 28, 45, 52, and 96 months after treatment respectively. There were no treatment-related deaths. This appears to be the only reported series of patients treated with a single agent in this situation. The results are comparable to those achieved by multi-agent regimens with autologous or allogeneic bone marrow transplantation.

Adult↗
PubMed1989

Dose-rate effects of mammary tumor development in female Sprague-Dawley rats exposed to X and gamma radiation.

Mammary tumour development was followed in two experiments involving a total of 2229 female Sprague-Dawley rats exposed to various doses of X or gamma rays at different dose rates. The data for another 462 rats exposed to tritiated water in one of these experiments were also analyzed. The incidence of adenocarcinomas and fibroadenomas at a given time after exposure increased linearly in proportion to total radiation dose for most groups. However, no significant increase in adenocarcinomas was observed with chronic gamma exposures up to 1.1 Gy, and the increase in fibroadenomas observed with chronic gamma exposures at a dose rate of 0.0076 Gy h-1 up to an accumulated dose of 3.3 Gy was small compared to that observed after acute exposures. The incidence of all mammary tumors increased almost linearly with the log of dose rate in the range 0.0076 to 26.3 Gy h-1 for 3 Gy total dose of gamma rays. The effects of X rays appeared to be less influenced by dose rate than were the effects of gamma rays.

Adenocarcinoma↗
PubMed1988

Chloroplast transformation in Chlamydomonas with high velocity microprojectiles.

Bombardment of three mutants of the chloroplast atpB gene of Chlamydomonas reinhardtii with high-velocity tungsten microprojectiles that were coated with cloned chloroplast DNA carrying the wild-type gene permanently restored the photosynthetic capacity of the algae. In most transformants of one of the mutants, a fragment with a 2.5-kilobase deletion was restored to normal size by a homologous replacement event; in about 25 percent of the transformants the restored restriction fragment was 50 to 100 base pairs smaller or larger than that of wild type. About one-fourth of the transformants of this mutant contained unintegrated donor plasmid when first examined. This plasmid persisted in four different transformants after 65 cell generations of continuous liquid culture but was lost from all transformants maintained on plates of selective medium. The restored wild-type atpB gene remains in all transformants as an integral part of the chloroplast genome and is expressed and inherited normally.

Chlamydomonas↗
PubMed1988

Staging laparotomy in Hodgkin's disease: a community hospital experience.

Between 1977 and 1984, 50 patients with Hodgkin's disease underwent a staging laparotomy performed by nine surgeons in a community hospital. Adequate procedures were performed in 80% of cases compared to staging laparotomies done between 1969 and 1976 when only 40% were properly performed. Abdominal lymphangiogram had a false-negative rate of 0 but a false positive rate of 70%. Clinical stage III disease was significantly downstaged at laparotomy (65% of cases). Postoperative complication rate was 4% and there were no operative deaths. A subset of patients not requiring laparotomy have been identified. Because the quality of staging laparotomy and lymphangiography was variable, we encourage all centres treating patients with Hodgkin's disease to review their own experience with these techniques before making individual patient treatment decisions.

Alberta↗
PubMed1988

Inhibitory effects of (S)-3-chlorolactaldehyde on the metabolic activity of boar spermatozoa in vitro.

(S)-alpha-Chlorohydrin and 3-chloro-1-hydroxyacetone inhibited the oxidative metabolism of fructose by boar spermatozoa only after a period of incubation in which they presumably underwent conversion to (S)-3-chlorolactaldehyde, an inhibitor of sperm glyceraldehyde 3-phosphate dehydrogenase. With glycerol as substrate, 3-chloro-1-hydroxyacetone had a similar effect, (S)-alpha-chlorohydrin was ineffective while (R,S)-3-chlorolactaldehyde was immediately effective with either substrate. All three compounds caused the accumulation of fructose 1,6-bisphosphate and dihydroxyacetone phosphate from fructose but not from glycerol which led to the conclusion that inhibition of triosephosphate isomerase was also associated with the anti-glycolytic action of (S)-3-chlorolactaldehyde. (S)-3-Chlorolactaldehyde caused the depletion of ATP in incubates of boar spermatozoa metabolizing fructose but not glycerol. This suggests that futile substrate cycling may play an important function in the anti-glycolytic action of (S)-3-chlorolactaldehyde and/or that boar spermatozoa can synthesize ATP from glycerol by a mechanism not involving the glycolytic pathway.

Acetone↗
PubMed1988

Is the nephrotoxicity of (R)-3-chlorolactate in the rat caused by 3-chloropyruvate?

1. When (R, S)-[3-36 Cl]chlorolactate was administered to male rats, two radioactive constituents were excreted in the urine. These were identified as 36Cl- and [3-36 Cl]chlorolactate which was subsequently shown to be essentially the (S)-isomer. 2. Analysis of the urinary oxalate content from rats receiving either (R)- or (S)-3-chlorolactate revealed that elevated levels were produced by the (R)-isomer whereas normal levels followed the administration of the (S)-isomer. 3. Treatment of (R,S)-3-chlorolactate with a modified Fenton's oxidizing system produced oxalate and an intermediate which was identified as 3-chloropyruvate. 4. 3-Chloropyruvate is a potent nephrotoxin in the rat producing a brief phase of diuresis when administered, increasing the urinary excretion of oxalate and inhibiting the oxidative metabolic capability of rat kidney tubules and rat kidney mitochondria in vitro. 5. Both (R)-3-chlorolactate and 3-chloropyruvate were shown to be inhibitors of the commercially-available pyruvate dehydrogenase complex. 6. 3-Chloropyruvate inhibits kidney mitochondrial metabolism possibly at the pyruvate dehydrogenase complex level and appears to be a metabolite of (R)- but not (S)-3-chlorolactate.

Animals↗
PubMed1987

Inhibition of triosephosphate isomerase in boar spermatozoa by (S)-3-chlorolactaldehyde.

Mature epididymal boar spermatozoa converted fructose and glycerol to carbon dioxide but in the presence of 3-chloro-1-hydroxyacetone these oxidations were inhibited. When the substrate was fructose, there was an increase in the amounts of fructose 1,6-bisphosphate and dihydroxyacetone phosphate but these glycolytic intermediates did not accumulate when glycerol was the substrate. Examination of enzyme activities in mature boar spermatozoa incubated with 3-chloro-1-hydroxyacetone, which is metabolised in vitro to (S)-3-chlorolactaldehyde, confirmed that glyceraldehyde 3-phosphate dehydrogenase and triosephosphate isomerase were both inhibited to equivalent degrees by this metabolite.

Aldehydes↗
PubMed1987

The renal toxicity of (R)-3-chlorolactate in the rat.

The renal toxicity of (R,S)-3-chlorolactate has been shown to be due to the (R)-isomer which, when administered to rats, induces diuresis and glucosuria. The metabolic activity of isolated tubule cells, prepared from rat kidney, was inhibited by (R)-3-chlorolactate and the action of the compound was localised as affecting mitochondrial metabolism. Studies with kidney mitochondria pin-pointed the site of action as being involved with the oxidative metabolism of malate but not the inhibition of mitochondrial malate dehydrogenase. The effects of oxalate, a metabolite of (R)-3-chlorolactate, and of (R,S)-3-chlorolactaldehyde on renal tubule cells was investigated. While some degrees of inhibition of metabolic activity were evident, these compounds were not responsible for the toxic effects produced by (R)-3-chlorolactate.

Acetyl Coenzyme A↗
PubMed1987

Pathologic Malgaigne fracture following pelvic irradiation. A case report.

A 48-year-old woman developed symptomatic superior and inferior pubic rami fractures with a concomitant subluxation of the ipsilateral sacroiliac joint three years after pelvic irradiation for a gynecologic malignancy. Pathologic pelvic fractures (PPF) caused by irradiation may be difficult to distinguish from those caused by metastatic disease. PPF produce prolonged disability.

Brachytherapy↗
PubMed1986

Bone marrow transplantation for acute monocytic leukemia following the treatment of Hodgkin's disease.

A 32-year-old woman developed acute monocytic leukemia within a year of treatment for Hodgkin's disease with chemotherapy and radiation. Residual leukemia was present in the bone marrow after two induction courses of high-dose Ara-C. She received a bone marrow transplant from an HLA- and DR-identical sister and remains in complete remission more than 2 years after transplantation. Only one other instance of a remission greater than 2 years after transplantation for secondary acute leukemia could be found in the literature. Although bone marrow transplantation may be carried out successfully in these patients, it is possible that they may be more vulnerable to transplant-related complications because of their previous exposure to chemotherapy and radiation. Only further study can clarify this matter and determine the best time for the procedure and which regimen should be used.

Adult↗
PubMed1986

Mechanism of inhibition of fructolysis in ram spermatozoa by chlorinated antifertility agents.

When ejaculated ram spermatozoa were incubated with (S)-alpha-chlorohydrin (up to 0.25 mM) the oxidative metabolism of fructose to carbon dioxide was inhibited in a concentration-dependent manner. This appears to be due to inhibition of glyceraldehyde-3-phosphate dehydrogenase which leads to the accumulation of fructose-1,6-bisphosphate, dihydroxyacetone phosphate and, to a lesser extent, glyceraldehyde-3-phosphate. (R)-alpha-Chlorohydrin (10 mM) had no significant effect on the oxidative metabolism of fructose. The inhibition of the oxidative metabolism of fructose by (S)-alpha-chlorohydrin (0.1 mM) was not immediate but was detected after incubation for 15 min. By contrast, (R,S)-3-chlorolactaldehyde (5 mM) caused an immediate inhibition of this metabolic pathway. 1-Chloro-3-hydroxyacetone (0.5 mM) immediately decreased the oxidative metabolism of fructose which resulted in the accumulation of key fructolytic intermediates in a manner comparable to that produced by (S)-alpha-chlorohydrin. At a concentration of 20 mM, 6-chloro-6-deoxyglucose had no significant effect on the metabolic activity of ram spermatozoa. We suggest that the anti-fructolytic actions of (S)-alpha-chlorohydrin and 1-chloro-3-hydroxyacetone are mediated via a common metabolite, (S)-3-chlorolactaldehyde, and that the inactivity of 6-chloro-6-deoxyglucose is due to the inability of ram spermatozoa to metabolise this chlorinated sugar to (S)-3-chlorolactaldehyde.

Acetone↗
PubMed1986

Inhibition of fructolytic enzymes in boar spermatozoa by (S)-alpha-chlorohydrin and 1-chloro-3-hydroxypropanone.

When boar spermatozoa were incubated with the (S)-isomer of the male antifertility agent alpha-chlorohydrin the activity of glyceraldehyde-3-phosphate dehydrogenase was inhibited. The (R)-isomer had no significant effect on the activity of this enzyme whereas (R,S)-3-chlorolactaldehyde caused an inhibition of its activity and also in that of lactate dehydrogenase. The in vitro production of (S)-3-chlorolactaldehyde, the active metabolite of (S)-alpha-chlorohydrin, was attempted by incubating boar spermatozoa with 1-chloro-3-hydroxypropanone. Preliminary results lead us to propose that this compound is converted into (S)-3-chlorolactaldehyde as well as to another metabolite which is an inhibitor of other enzymes within the fructolytic pathway.

Acetone↗