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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 667 records · Page 37Linked to original sources

KP1: a new monoclonal antibody that detects a monocyte/macrophage associated antigen in routinely processed tissue sections.

A new monoclonal antibody, KP1, raised against a lysosomal fraction of human lung macrophages, recognises a fixation-resistant epitope in a wide variety of tissue macrophages (such as Kupffer cells germinal centre, splenic, and lamina propria macrophages), and in granulocyte precursors. Its broad reactivity with cells of the mononuclear phagocytic lineage was established by testing on routinely processed samples of normal and reactive lymphoid tissues. Interdigitating reticulum cells were unstained or showed limited cytoplasmic staining while Langerhans' cells and follicular dendritic reticulum cells were unreactive. KP1 recognises a molecule of about 110 kilodaltons in macrophage-rich human tissue when tested by either immunoprecipitation or Western blotting (although the latter procedure also shows two additional components with molecular weights of 70 and 40 kilodaltons). KP1 should be of considerable value for studying disorders of the monocyte/macrophage system, including both reactive and neoplastic states (such as true histiocytic proliferations).

Antibodies, Monoclonal↗

Quality of parenting in alcoholics and narcotic addicts.

Alcoholics and heroin addicts were compared with a normal control group to determine whether there were differences in quality of parenting during childhood, assessed using the Parental Bonding Instrument. Maternal and paternal overprotection were reported more commonly by narcotic addicts. Maternal overprotection alone was implicated in alcoholics. Narcotic addicts seem to have more disturbed parenting than alcoholics, especially paternal parenting.

Adult↗

Increased fibronectin production by cell lines from hypertrophic scar and keloid.

Primary cell lines of fibroblasts from 8 tissues were established--three from hypertrophic scars (HS), one keloid (K) and four from the normal uninvolved dermis adjacent to each lesion. The objective was to quantify and compare all eight cell lines on the basis of fibronectin (FN) produced per cell and per total protein (PR). Two hypertrophic scars and their adjacent skin cell lines were evaluated by the ELISA method for FN and a micro Lowry assay for PR. The scar lines showed statistically significant increases in the amount of FN/cell compared to the cell lines from their adjacent normal dermis. The third hypertrophic scar and the keloid with their adjacent skin cell lines were assayed for FN and PR by radioimmunoprecipitation. Subconfluent cells were metabolically labeled with 35S-methionine for 20 hours. Harvested media and cell monolayers were assayed for radioactivity incorporated into FN and PR. The percentage of FN/PR was significantly higher in media for HS and K compared to the adjacent normal skin lines in the three passages tested. These results support our previous immunofluorescence studies and demonstrate that a fibroblast-type cell line from a hypertrophic scar or keloid produces more FN/PR over time than the normal fibroblast-type cell line from adjacent uninvolved dermis.

Cell Line↗

Metabolism and disposition studies with a [35S]-labelled growth promotor: bis(N1-methyl-N2-methylsulphonyl) guanidinylethyl] disulphide.

The disposition and metabolism of the [35S]-labelled growth promotor bis[N1-methyl- N2-methylsulphonyl) guanidinylethyl] disulphide was studied in the rat following oral administration. There was rapid and significant absorption of drug-derived products evidenced by maximum concentrations for plasma and the majority of sampled tissues at 1 h post dose, and extensive renal clearance, with greater than 62% of dose voided in urine in 12 h. Analysis of urine revealed that the administered compound had been completely metabolised to five metabolites of which the two major products have been characterised. A metabolic pathway involving reductive cleavage of the disulphide bond, followed by S-methylation and sulphoxidation would appear to be involved in the biotransformation of the compound.

Animals↗

A modified method for human bone marrow filtration prior to bone marrow transplantation.

A technique is described for filtering harvested bone marrow using disposable materials, namely a 4 x 4 inch piece of sterile gauze that is gently packed into the barrel of a 60-ml plastic disposable syringe, which is connected directly to a blood collection bag. The filtration of marrow directly into the collection bag eliminates additional filtration steps and therefore may potentially reduce the incidence of inadvertent microbial contamination. In this study we describe this filtering technique and compare it to the method described by Thomas and Storb. Numbers of granulopoietic progenitors (CFU-GM) and erythropoietic progenitors (BFU-E), total white cell counts, percentage of cells positive for the CD3 (OKT3) lymphocyte surface membrane marker, and volume changes were studied following filtration by each method. The two techniques were shown to be comparable in terms of these parameters. Furthermore, when compared with historical controls, this method resulted in a reduced incidence of microbial contamination compared to filtration using successive stainless steel screens.

Adolescent↗

HLA haplotype A1 B8 DR3 as a risk factor for HIV-related disease.

Of 32 patients exposed to a single batch of factor VIII contaminated with human immunodeficiency virus (HIV), 18 became antibody positive. Serial T cell subset analyses over the succeeding four years have shown a progressive decline in circulating T4 cells in those 18 but no change in the 14 who remain seronegative. 2 of the seroconverters have died and a further 7 have symptoms attributable to HIV infection. In the group as a whole, the HLA haplotype A1 B8 DR3 was weakly associated with an increased risk of seroconversion on exposure to the virus while, in those who seroconverted, it was strongly associated with a rapid decline in T4 cells and development of HIV-related symptoms within four years of infection.

Adult↗

Influence of the subendothelial basement membrane components on fibrin assembly. Evidence for a fibrin binding site on type IV collagen.

Effective repair of a vascular injury depends on establishment of a stable fibrin patch at the injury site. Data presented in this study demonstrate that structural modification of fibrin occurs as a result of fibrin interaction with naturally occurring components of the vascular basement membrane and subendothelial structures. Of the basement membrane components, type IV collagen produces the greatest structural modification, generating thick fibrin fibers; a 3-fold increase in the fiber mass/length ratio occurs when type IV collagen is increased from 0 to 100 ng/ml. Laminin and dermatan sulfate decrease the fibrin fiber mass/length ratio resulting in thinner fibers. However, the overall effect of the basement membrane on fibrin is to increase the fibrin fiber diameter. Electrophoretic light scattering and the binding of type IV collagen by fibrinogen-Sepharose further establish the interaction between type IV collagen and fibrinogen. Incorporation of laminin with type IV collagen onto coated surfaces decreases the ability of type IV collagen to bind fibrinogen. These studies emphasize that the final fibrin structure is influenced by the milieu in which the clot is assembled.

Basement Membrane↗

Contribution of gut bacterial metabolism to human metabolic disease.

Metronidazole, an antibiotic with specific activity against anaerobic bacteria, was of clinical and biochemical benefit in two patients with methylmalonic aciduria. The virtual elimination of propionic acid from the stool suggested that propionic acid derived from faecal bacterial metabolism contributes substantially to methylmalonate production. These findings point to a novel avenue of treatment for these disorders of intermediary metabolism, and indicate the importance of microbial gut flora in normal human metabolism.

Bacteria, Anaerobic↗

Graft-versus-host reaction-induced immune modulation. I. Donor-recipient genetic disparity and the differential expression of Lyt-2, L3T4, and Ly-6 during acute reactions in the host thymus.

To investigate the effects of graft-vs-host reactions (GvHR) on cells in a central lymphoid compartment, GvHR were induced across class I/II or class II only major histocompatibility complex differences utilizing the parent into nonirradiated F1 hybrid (P----F1) model. Thymocytes were subsequently examined during the acute stage of GvHR for the expression of Lyt-2, L3T4, and Ly-6 cell surface molecules. Class I/II "suppressive" GvHR resulted in a dramatic decrease (greater than 85%) in total thymocyte numbers by 2 wk after parental cell injection. Although a dramatic decrease in the percentages of Lyt-2 (85%----30%) and L3T4 (95%----50%) expression was observed, the percentage of thymocytes expressing Ly-6 was markedly increased compared to uninjected controls (5%----greater than 80%). This increased percentage was not due solely to a selective loss of Ly-6 negative cells from the thymus, since the actual number of Ly-6 positive cells was greater in GvHR mice than in controls. Class II GvHR during the same time interval resulted in a less dramatic decrease (20 to 60%) in total thymocyte numbers. In addition, the effect on the percentages of Lyt-2 (85%----approximately 70%) and L3T4 (95%----approximately 85) expression was subtle and transient. However, intrathymic Ly-6 expression was again clearly enhanced (5%----20 to 30%). Class I/II "proliferative" or "stimulatory" GvHR differ from "suppressive" reactions in that they are characterized by stimulatory pathologic symptoms and the appearance of autoimmune abnormalities. Such GvHR were found to result in minimal alteration of total thymocyte numbers. Similarly, the percentage expression of Lyt-2 and L3T4 was marginally affected. However, the percentage of Ly-6 expression was increased from 5%----20 to 30% and thus these intrathymic lymphocyte profiles more closely resemble those of class II as compared to class I/II "suppressive" GvHR. The present findings therefore demonstrate that major histocompatibility complex differences alone do not necessarily determine the effects of GvHR on recipient thymocytes and that Ly-6 is a useful marker for the early detection of GvHR-associated immunologic events.

Animals↗

Comparative distribution and excretion of carboplatin and cisplatin in mice.

The comparative distribution and excretion of Carboplatin (cis-diammine-1,1-cyclobutane dicarboxylate platinum II, CBDCA, JM8) and cisplatin have been investigated in Balb C- mice following i.v. administration of the maximally tolerated doses (MTDs) of the compounds. Although the concentrations of platinum in the plasma and tissues during the alpha-phase were much higher for Carboplatin than for cisplatin, reflecting the difference in the doses used (4 vs 80 mg/kg), the tissue-to-plasma ratios were similar. During the beta-phase (1-10 days), however, both the platinum concentrations and the ratios were found to be similar for most tissues when cisplatin and Carboplatin were compared. The platinum concentrations and the tissue-to-plasma ratios of the spleen, brain, muscle, testes, ovary and bile, on the other hand, were consistently higher (two- to sixfold) after Carboplatin than after cisplatin. The highest ratios (greater than 20) were found in the kidney, liver, spleen (after Carboplatin only) and skin at 6 days after treatment. Comparison of the two compounds showed that the half-lives of platinum in the plasma and tissues during both the alpha- and beta-phases were similar, except for the spleen, in which a nine-fold greater t1/2 beta was recorded for Carboplatin than for cisplatin. The main route of excretion for the two complexes is via the kidneys, with 52% of cisplatin and 93% of Carboplatin being excreted during the first 3 days. The major part of this, however, is excreted within the 1st day. These results indicate that, although there are quantitative differences, the distribution and excretion profiles are similar for Carboplatin and cisplatin.

Animals↗

Two membrane-bound proteins associated with alanine resistance and increased A-system amino acid transport in mutants of CHO-K1.

Growth of CHO-K1, a proline auxotroph, is inhibited by amino acids that prevent proline transport. From a hydroxyurea-treated, alanine-resistant, constitutive mutant, alar4, we isolated, in a stepwise fashion, mutants, resistant to higher concentrations of alanine, that have increased velocity of amino acid transport through the A system. Two such mutants, alar4-H2.1 and alar4-H3.9, isolated as resistant to 50 mM and 125 mM alanine, respectively, showed increases in Vmax of proline transport through the A system that are directly proportional to their resistance to alanine. Alar4-H3.9, as compared to alar4 and CHO-K1, has six and 29 times the Vmax of proline transport through the A system and two and five times the velocity of transport through the combined ASC and P systems, respectively, and no change in system L. No double-minute or homologous staining regions were detectable in alar4-H3.9. A-system activity of alar4-H2.1 and alar4-H3.9, when grown under nonselective conditions, was stable for 20 generations and then declined. The phenotype of alar4-H3.9 is codominant with that of alar4 and partially recessive to that of CHO-K1. Membrane vesicles prepared from alar4-H3.9 show increases mainly in A-system transport. In sodium dodecylsulfate-polyacrylamide gel electrophoresis analysis of A-system active membrane vesicles and endoplasmic reticulum, two bands of molecular weight of approximately 62-66 kd and 29 kd are present in higher concentrations in alar4-H3.9 than in CHO-K1. These results are compatible with the hypothesis that the phenotype of alar4-H3.9 is the result of gene amplification of an A-system transporter structural gene and that the two bands may represent this transporter.

Alanine↗

The effects of fetal energy depletion on amniotic fluid concentrations of amino acids, organic acids and related metabolites.

Concentrations of amino and organic acids, phosphate, sulphate, gluconic acid and gluconolactone were measured in amniotic fluid samples which contained either normal or raised hypoxanthine concentrations. In this way, the effect of mild fetal ATP depletion could be determined. The effects of this mild asphyxia were to raise concentrations of phenylalanine, tyrosine, lysine, glycine, phosphate, sulphate, gluconic acid and glucono-1,5-lactone. However, concentrations of a variety of other metabolites were unchanged; thus no diagnostic confusion should arise with organic acidurias in mild asphyxia in contrast to the biochemical mimickry produced by severe asphyxia. Since clinically normal parturition can produce changes in amniotic fluid, urine from newborn or cord blood may not reflect the metabolic balance in utero.

Adenosine Triphosphate↗

Influence of minoxidil on myocardial hemodynamics, regional blood flow, and morphology in beagle dogs.

Studies were made of the effects of two doses of minoxidil (3 mg/kg), given 24 hours apart, on cardiovascular hemodynamics, regional myocardial blood flow, and cardiac morphology in beagle dogs. Minoxidil caused increases in mean right atrial and left ventricular end-diastolic pressure. Systemic and pulmonary vascular resistance were reduced; cardiac output was increased. Left ventricular stroke work and the systolic pressure time index were unchanged by monoxidil administration. The diastolic pressure time index and ratio of diastolic/systolic pressure time index were decreased by minoxidil. Regional myocardial blood flow, measured with radioactive microspheres, increased in all regions of the heart except to the left ventricular papillary muscles. Minoxidil increased blood flow to left ventricular subendocardial tissue; however, this increase was significantly less than that observed in corresponding areas of subepicardial tissue, thus reducing the subendocardial/subepicardial tissue blood flow ratio. These results suggest that minoxidil is an effective peripheral vasodilator but may result in inadequate subendocardial perfusion. Morphologic studies disclosed two types of minoxidil-induced cardiac lesions: left ventricular papillary muscle necroses, and hemorrhagic lesions which were most prominent in right atrium and were associated with inflammation, intramural hemorrhage, and fibrinoid necrosis of small arteries. The papillary muscle necrosis were attributed to hypoxia. The atrial lesions were not of ischemic or hypoxic origin, because minoxidil did not decrease blood flow to atrial tissue. It is suggested that the atrial lesions are related to excessive vasodilation.

Animals↗