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Biomedical subjects

A R Jones

Publications and source records attributed to A R Jones.

At least 55 records · Page 3Linked to original sources

Metabolism of 36Cl-ornidazole after oral application to the male rat in relation to its antifertility activity.

1. The antimycotic ornidazole (a male antifertility agent in rats) was synthesized incorporating 36Cl in the chloropropyl sidechain and its metabolism was investigated in the male rat after oral ingestion. 2. Blood levels of radioactivity were low over the first 24 h and there was no tissue accumulation of radioactivity over 48 h. 3. Most of the excreted radioactivity (20% of the ingested dose) appeared in the urine within the first 24 h. 4. Three major compounds were detected in 0-24-h urine samples and were characterized as ornidazole (13% of total radioactivity), Cl- (22%) and 3-chlorolactate (30%), the oxidation product of 3-chlorolactaldehyde. 5. No polyuria or glucosuria was observed following the oral administration of ornidazole, suggesting that any (R)-3-chlorolactate produced was insufficient to affect renal metabolism. 6. Conversion of ornidazole initially to (R, S)-alpha-chlorohydrin or ultimately to the glycolytic inhibitor (S)-3-chlorolactaldehyde could explain its antifertility action in the male rat.

Administration, Oral↗

Endogenous energy production by mature boar spermatozoa.

When incubated in the absence of exogenous substrates, washed boar spermatozoa maintained a high energy charge potential (ECP) for at least 5 h. Addition of 3-chloro-1-hydroxypropanone, an inhibitor of triosephosphate isomerase and glyceraldehyde 3-phosphate dehydrogenase, at any time caused the ECP to decline and fructose-1,6-bisphosphate, dihydroxyacetone phosphate and glycerol to accumulate. There appear to be two endogenous substrates that are degraded ultimately to produce the triosephosphates which allow the cells to produce lactate for the mitochondrial synthesis of ATP. One substrate generates minor amounts of glycerol 3-phosphate whereas the other substrate degrades to glycerol and may be di-glycerides, or tri-glycerides, or both.

Acetone↗

GLD-1, a cytoplasmic protein essential for oocyte differentiation, shows stage- and sex-specific expression during Caenorhabditis elegans germline development.

GLD-1, a putative RNA binding protein, is essential for oocyte development in Caenorhabditis elegans. A gld-1 null mutation abolishes hermaphrodite oogenesis and confers a tumorous germline phenotype in which presumptive female germ cells exit the meiotic pathway and return to the mitotic cell cycle. Here we demonstrate that gld-1(null) germ lines express female-specific, but not male-specific, molecular markers, indicating that gld-1 acts downstream of sexual fate specification to regulate oocyte differentiation. Immunolocalization studies identify GLD-1 as a cytoplasmic germline protein that displays differential accumulation during germline development. First, germ cells that are in the mitotic cell cycle contain low levels of GLD-1 that likely reflect a nonessential gld-1 function (negative regulation of proliferation in the mitotic germ line) revealed in previous genetic studies. Second, entry of presumptive oocytes into the meiotic pathway is accompanied by a strong increase in GLD-1 expression/accumulation. GLD-1 levels are high through the pachytene stage but fall to background as germ cells exit pachytene and complete oogenesis. The meiotic prophase accumulation pattern is consistent with GLD-1's essential role in oocyte differentiation, which may be to repress the translation of a subset of maternal RNAs synthesized during early oogenesis until late oogenesis when GLD-1 is absent.

Animals↗

Diurnal change of blood count analytes in normal subjects.

Short-term, within one 24-hour day (diurnal period) within-person changes of the principal blood count analytes in healthy subjects were studied at three major institutions. The results from each test site were indistinguishable and were therefore combined to make a database of 96 healthy subjects. Analytical imprecision of each analyte was subtracted from the total observed variation to give true diurnal change. Each analyte showed characteristic changes. As would be expected, cellular properties of erythrocytes, such as MCV (mean cell volume) and MCH (mean cell hemoglobin) showed negligible change. The red cell count, hematocrit, and hemoglobin showed changes that were consistent with fluid balance change. Total white cell count and some differential count components showed major changes that raised questions of the confidence limits of clinical decision levels and the validity of commonly used reference intervals. Platelet count changes were typically less than analytic imprecision, suggesting the need for improvement in this aspect of analyzer performance.

Blood Cell Count↗

Metabolism of glycerol 3-phosphate by mature boar spermatozoa.

Under anaerobic conditions boar spermatozoa metabolized fructose and glucose to lactate but did not produce ATP to the extent of that produced under aerobic conditions; the ketogenic amino acids leucine, tryptophan, phenylalanine and tyrosine were not oxidatively metabolized. Glycerol 3-phosphate was metabolized rapidly in the presence or absence of the glycolytic inhibitor, 3-chloro-1-hydroxypropanone (CHOP). In the absence of CHOP, glycerol 3-phosphate was converted to CO2, lactate, glucose 6-phosphate and fructose 6-phosphate, and ATP was produced. In the presence of CHOP, glycerol 3-phosphate did not produce CO2, lactate or ATP, but formed fructose 1,6-bisphosphate and dihydroxyacetone phosphate. With dihydroxyacetone phosphate as substrate, fructose 1,6-bisphosphate, lactate, glucose 6-phosphate, fructose 6-phosphate and ATP were produced. Accumulation of glucose 6-phosphate and fructose 6-phosphate from glycerol 3-phosphate appeared to depend on the production of ATP; if ATP was not produced, dihydroxyacetone phosphate and fructose 1,6-bisphosphate accumulated. The conversion of glycerol 3-phosphate to glycolytic intermediates appeared to be a mechanism for the conversion of substrates for the ultimate production of lactate.

Acetone↗

Glycerol 3-phosphate dehydrogenase of boar spermatozoa: inhibition by alpha-bromohydrin phosphate.

Boar spermatozoa incubated with glycerol 3-phosphate as substrate produced CO2 and an accumulation of dihydroxyacetone phosphate and fructose-1,6-bisphosphate. The rate of oxidation of glycerol 3-phosphate was decreased, as was the production of CO2 and the two glycolytic intermediates, in the presence of (R,S)-alpha-bromohydrin phosphate. In the presence of inhibitors of stage two of the glycolytic pathway, CO2 production was prevented, there was a marked increase in the concentration of the glycolytic intermediates but the rate of metabolism of the substrate was unaffected. Oxygen consumption by spermatoza incubated with glycerol 3-phosphate was unaffected in the presence of rotenone, whereas it was decreased when lactate was offered as the substrate. The results reported here confirm that in boar spermatozoa glycerol 3-phosphate dehydrogenase is an FAD-linked enzyme that is inhibited by (R,S)-alpha-bromohydrin phosphate in, possibly, a competitive manner.

Animals↗

Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68.

The gld-1 gene of Caenorhabditis elegans is a germ-line-specific tumor suppressor gene that is essential for oogenesis. We have cloned the gld-1 gene and find that it encodes two proteins that differ by 3 amino acids. The predicted proteins contain a approximately 170-amino-acid region that we term the GSG domain (GRP33/Sam68/GLD-1), on the basis of significant similarity between GLD-1, GRP33 from shrimp, and the Src-associated protein Sam68 from mouse (also described as GAPap62 from humans). A conserved structural motif called the KH domain is found within the larger GSG domain, suggesting a biochemical function for GLD-1 protein in binding RNA. The importance of the GSG domain to the function of gld-1 in vivo is revealed by mutations that affect 5 different conserved GSG domain residues. These include missense mutations in an absolutely conserved residue of the KH domain that eliminate the tumor suppressor function of gld-1.

Amino Acid Sequence↗

Inhibition of glycolysis in boar spermatozoa by 1,6-dichloro-1,6-dideoxy-D-fructose.

The dichloro-analogue of D-fructose 1,6-bisphosphate, 1,6-dichloro-1,6-dideoxy-D-fructose, is a weak substrate for boar sperm aldolase which converts it to (S)-3-chlorolactaldehyde and 3-chloro-1-hydroxypropanone in vitro. Production of these chloro-trioses leads to the strong inhibition of glyceraldehyde-3-phosphate dehydrogenase, the weak inhibition of triosephosphate isomerase and the transient inhibition of aldolase.

Animals↗

Microvessel endothelial cells and pericytes increase proliferation and repress osteoblast phenotypic markers in rat calvarial bone cell cultures.

To investigate the influence of microvessel cells on osteoblasts, we exposed osteoblast-enriched cultures of rat calvarial cells to cultured endothelial cells and pericytes using feeder-layer co-cultures, co-culture dish inserts, and conditioned media experiments. When co-cultured with growth-arrested feeder-layers of endothelial cells or pericytes for 10 days, bone cell cultures showed an increase in cell number and reduction in alkaline phosphatase activity. The response of bone cells to endothelial cells was nearly twice their response to pericytes. A similar response was demonstrated by exposure to microvessel cells in co-culture dish inserts and by exposure to media conditioned by microvessel cells. In long-term cultures of bone cells, the levels of osteocalcin and the number of mineralized nodules both were reduced by exposure to media conditioned by the microvessel cells. Transient exposure to conditioned media from the microvessel cell cultures for 3 days, during the period from initial plating to cell confluence, produced nearly the same effect on the cultures of bone cells as did continuous exposure to these conditioned media. The influence of isolated microvessel cells on osteoblast-enriched calvarial cells was found to be primarily mitogenic, mediated by soluble factors, independent of cell contact, and a cause of prolonged reduction in the expression of early and late markers of the osteoblast phenotype.

Animals↗

The anti-glycolytic activity of 3-bromopyruvate on mature boar spermatozoa in vitro.

Mature epididymal boar spermatozoa converted fructose, glycerol and glycerol-3-phosphate to carbon dioxide, but in the presence of 0.5 mM 3-bromopyruvate, these oxidations were inhibited while that of lactate was unaffected. Inhibition of the oxidation of these substrates results in a decrease in the content of ATP and the accumulation of dihydroxyacetone phosphate and fructose-1,6-bisphosphate. Examination of the activities of the enzymes within stage two of the glycolytic pathway showed that glyceraldehyde-3-phosphate dehydrogenase and 3-phosphoglycerate kinase were immediately inhibited by 3-bromopyruvate in a competitive manner. We now report the action of 3-bromopyruvate on the metabolic activity of boar spermatozoa. At a concentration of 0.5 mM, this compound selectively inhibits stage two of the glycolytic pathway and becomes yet another specific inhibitor of spermatozoal metabolism.

Adenosine Triphosphate↗

The aetiology and distinguishing features of solitary spinal hot spots on planar bone scans.

PURPOSE: To determine the aetiology of solitary spinal hot spots on planar bone scans and to determine which radiographic and scintigraphic features aid in distinguishing benign from malignant lesions. MATERIALS AND METHODS: 81 bone scans showing a solitary hot spot in the spine were identified. Aetiology was determined in 73 based on imaging and clinical findings, including clinical follow-up. The location of the hot spot was classified as paravertebral (related to the lateral spinal margin), panvertebral (diffuse uptake confined within a vertebra), hemivertebral (uptake confined between the midline and lateral spinal margin) or complex (all others). RESULTS: The aetiology of the spinal hot spot was benign in 55 patients and malignant in 18. The latter all belonged to the subgroup of 42 patients with a known malignancy. Only eight of the 18 malignant cases had suggestive plain radiographic findings. There was no significant relationship between aetiology and age. The spinal level of the hot spot was cervical in three (all benign), thoracic in 16 (eight benign) and lumbar in 54 (44 benign). The hot spot was paravertebral in 21 (all benign), panvertebral in 24 (20 benign), hemivertebral in 13 (10 benign) and complex in 15 (only four benign). CONCLUSIONS: Most (75%) solitary spinal hot spots are benign, and even in patients with known malignancy just over half (57%) are benign. Malignant lesions are often (56%) radiographically occult. Thoracic or complex hot spots are more likely to be malignant while paravertebral hot spots are characteristically benign. These features may be helpful in distinguishing benign and malignant lesions in patients with a known malignancy and unremarkable radiographs. Other scintigraphic features are unhelpful in distinguishing benign from malignant lesions.

Adolescent↗

Mycobacterium avium complex (MAC) osteomyelitis and septic arthritis in an immunocompetent host.

We describe a case of Mycobacterium avium complex (MAC) osteomyelitis and septic arthritis in an immunocompetent man. Infection was derived from a chainsaw injury sustained on the lateral aspect of the ankle 13 years earlier, and had spread through the bone, joint and soft tissue emerging at the medial aspect. This was successfully treated with surgical debridement, drainage, arthrodesis and 18 months of chemotherapy consisting of clarithromycin, rifampicin, ethambutol, and ciprofloxacin with an initial 2 weeks of amikacin. Infections with this organisms are generally associated with immunocompromised states, particularly advanced AIDS. However, our patient illustrates that atypical mycobacterial infections must also be considered in immunocompetent patients who have a prolonged clinical course and an appropriate potential source of infection.

Adult↗

Inhibition of glyceraldehyde 3-phosphate dehydrogenase in boar spermatozoa by bromohydroxypropanone.

In the presence of 3-bromo-1-hydroxypropanone (BOP), cauda epididymal sperm obtained from mature boars produced a carbonyl compound which is assumed to be (S)-3-bromolactaldehyde. Glyceraldehyde 3-phosphate dehydrogenase was rapidly inhibited which resulted in the accumulation of dihydroxyacetone phosphate and fructose-1,6-bisphosphate, and no accumulation of lactate when fructose was the substrate. The energy charge potential of the cells declined in the presence of BOP when either fructose or glycerol were substrates. It is suggested that BOP is transformed into (S)-3-bromolactaldehyde, which is the actual inhibitor of glyceraldehyde 3-phosphate dehydrogenase, thus demonstrating BOP to be the first brominated chemical to have an anti-glycolytic action on mature sperm in vitro.

Acetone↗

Inhibition of glycolysis in boar spermatozoa by alpha-chlorohydrin phosphate appears to be mediated by phosphatase activity.

(R,S)-alpha-chlorohydrin-1-phosphate, previously shown to have no anti-glycolytic activity on mature boar sperm in vitro, is a substrate for acid and/or neutral phosphatase(s) that are associated with washed sperm. The high phosphatase activity hydrolyses the ester to alpha-chlorohydrin which undergoes oxidation to (S)-3-chlorolactaldehyde, a specific inhibitor of sperm glyceraldehyde-3-phosphate dehydrogenase and triosephosphate isomerase, thereby exhibiting an anti-glycolytic action.

Animals↗