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Biomedical subjects

J C Moore

Publications and source records attributed to J C Moore.

At least 73 records · Page 4Linked to original sources

Neuron development in the superior colliculus of the fetal mouse following maternal alcohol exposure.

Pregnant Swiss Webster mice were given a liquid diet with ethanol (EtOH) or isocaloric amounts of maltose dextrin on gestation day (GD) 0 through 18. On GD 18, maternal blood samples were obtained. Fetuses were then removed and fetal brains were prepared for light microscopy. Fetal weight was reduced in the EtOH-exposed group. The ratio of midbrain cross sectional area to cerebral aqueduct was reduced in the ethanol group, while the density of neuronal nuclear population in both the dense outer layer (DS) and sparse inner layer (SS) of the developing superior colliculus was increased. Mean nuclear volume was decreased in the SS.

Animals↗

Relationship between platelet aggregating factor and von Willebrand factor in thrombotic thrombocytopenic purpura.

The pathophysiology of the platelet thrombotic disorder, thrombotic thrombocytopenic purpura (TTP), is not well understood. Two apparently unrelated laboratory abnormalities have recently been described in patients with TTP: a platelet aggregating factor and abnormalities in von Willebrand factor (vWF). Although an interaction between these two abnormalities has been postulated to participate in the disease, this has not been proved. In this report we describe studies on a patient with relapsing TTP. These studies demonstrate that a consistent relationship exists between the platelet aggregating factor present in the patient's serum and vWF. The patient had chronic low-grade thrombocytopenic and schistocytic haemolytic anaemia that could be temporarily cured by infusions of plasma and certain other blood products. During acute exacerbations of the illness, a platelet aggregating factor was detectable in the patient's serum and this was associated with the loss of the larger multimers of vWF. During remissions of the illness, abnormally large multimers of vWF were present. The results of this study support the concept that a platelet aggregating factor plus large multimers of vWF participate in the acute platelet thrombi that characterize TTP.

Anemia, Hemolytic↗

Calcium-dependent cysteine protease activity in the sera of patients with thrombotic thrombocytopenic purpura.

Plasma and serum from patients with thrombotic thrombocytopenic purpura (TTP) can cause activation and aggregation of normal human platelets in vitro. It is possible that this platelet-activating factor contributes to the disease. In this report we describe studies designed to identify the platelet-activating factor in TTP. Platelet activation by sera from 15 patients with TTP was inhibited by leupeptin, iodoacetamide, and antipain but not by phenylmethylsulphonylfluoride, epsilon-aminocaproic acid, soybean trypsin inhibitor, aprotinin, and D-phenylanyl-1-prolyl-1-arginine chloromethyl ketone. These studies suggested that the platelet-activating factor in TTP serum was a cysteine protease. We confirmed that a calcium-dependent cysteine protease (CDP) was present in the sera of each of the 15 patients when we used an assay based on the ability of CDP to proteolyse platelet membrane glycoprotein 1b (GP1b) and hence to abolish the ability of CDP-treated normal platelets to agglutinate in the presence of ristocetin and von Willebrand factor. This proteolytic activity was inhibited by EDTA, leupeptin, antipain, iodoacetamide, and by N-ethyl-maleamide (NEM) but not by the serine protease inhibitors. Activity was detected in 15 of 15 patients with TTP tested before therapy was begun. In contrast, no activity was detected in the serum of any of five of the TTP patients tested in remission or in any of the sera from 36 patients with thrombocytopenia and 423 nonthrombocytopenic controls. To look for in vivo CDP activity in patients with TTP, we studied platelets from two patients with acute TTP (drawn into acid-citrate-dextrose, NEM, and leupeptin). These platelets showed a loss of GP1b from the platelet surface. Both patients were also studied in remission: GP1b on the platelet surface had returned to normal. These studies provide evidence that CDP is present in the sera of patients with TTP, that it is specific to this disease, and that is is active in vivo as well as in vitro. We postulate that a disorder of CDP homeostasis plays a major role in the pathophysiology of TTP.

Blood Platelets↗

Studies investigating platelet aggregation and release initiated by sera from patients with thrombotic thrombocytopenic purpura.

Many patients with thrombotic thrombocytopenic purpura (TTP) have a platelet aggregating factor in their serum that may be pathologically linked with the disease process. To help characterize the type of platelet aggregation and platelet release induced by the sera from seven TTP patients, we measured the ability of a variety of inhibitors of platelet function as well as the ability of monoclonal antibodies (MoAbs) against platelet glycoproteins to inhibit TTP sera-induced platelet aggregation and release. These results were compared with the ability of the same inhibitors to block platelet aggregation induced by ristocetin, collagen, ADP, thrombin, and IgG-immune complexes. Monoclonal antibody directed against platelet glycoprotein Ib totally inhibited ristocetin-induced aggregation and release but had no effect on aggregation and release induced by the TTP sera or by any of the other platelet agonists. However, the MoAb against glycoproteins IIb/IIIa inhibited aggregation and release caused by TTP sera as well as by collagen, thrombin, and ADP but had no effect on aggregation and release induced by ristocetin. The aggregating activity could be abolished by heparin but not by the serine protease inhibitor PMSF (1 mmol/L). And although monomeric human IgG and purified Fc fragments of IgG inhibited IgG-immune complex-induced aggregation and release, they had no effect on TTP sera-induced aggregation and release nor on aggregation and release induced by any of the other agonists. Consistent with these in vitro studies showing no effect of IgG were the in vivo observations that intravenous (IV) IgG was without effect when administered to three patients with TTP. This study indicates that although a von Willebrand factor (vWF)-rich preparation of cryoprecipitate enhances the in vitro platelet aggregation and release caused by sera from the seven TTP patients we studied, the pathway of aggregation and release is not via platelet glycoprotein Ib. Also the aggregating factor of TTP sera is not neutralized in vitro or in vivo by IgG.

Adenosine Diphosphate↗

Effects of aerial thermal fog applications of fenthion on caged pink shrimp, mysids and sheepshead minnows.

Mosquito control applications of fenthion by aerial thermal fog equipment were studied at 2 sites in Collier County, FL, for sprays that occurred on June 20 and 23, 1984. Acute, lethal effects of fenthion deposited in these estuarine habitats were assessed for caged pink shrimp (Penaeus duorarum), mysids (Mysidopsis bahia) and sheepshead minnows (Cyprinodon variegatus). At Site 1, along a bay with substantial dilution and tidal mixing, fenthion concentrations of 1.5 and 0.29 micrograms/liter were measured in samples taken immediately after both sprays. Concentrations decreased to less than or equal to 0.020 microgram/liter 12 h postspray and no mortality was observed for caged pink shrimp and mysids. Site 2 was along a residential canal system that offered limited dilution and mixing. Maximum concentrations were 2.6 and 0.51 micrograms/liter and measurable concentrations (greater than 0.038 microgram/liter) of fenthion persisted at this site for 4 days. Fenthion concentrations in surface waters were toxic to caged pink shrimp and mysids after both sprays. No mortality occurred among caged sheepshead minnows at either site.

Animals↗

Glycosylated haemoglobin: comparison of five different methods, including measurement on capillary blood samples.

Glycosylated haemoglobin was measured in venous blood samples and in blood collected in 'Unistep' bottles by isoelectric focusing (IEF), as the reference method, and by electroendosmosis (EEO), the thiobarbituric acid method (TBA), ion-exchange chromatography (IEC) and affinity chromatography (AC). Isoelectric focusing, electroendosmosis and thiobarbituric acid gave similar results. Affinity chromatography gave lower results than isoelectric focusing for normal values but similar results for diabetics. Ion-exchange chromatography gave 24% lower results than isoelectric focusing across the range. Using Unistep collected blood samples and comparing multiple samples from the same patient, electroendosmosis gave the best results (coefficient of variation 4%) and thiobarbituric acid gave slightly less good precision that other methods. Re-use of affinity chromatography columns gave less good precision. Collection of blood samples into a Unistep bottle gave similar results to venous sample results. Storage of venous capillary blood samples in Unistep bottles over 1 week at 21 degrees C gave similar results to immediate assay. Electroendosmosis of blood samples in Unistep bottles gave stable results over 2 weeks. Home collection by a patient of a capillary blood sample into a Unistep bottle allows glycosylated haemoglobin results to be available when seen in the clinic.

Capillaries↗

Glycosylated plasma protein measurement by a semi-automated method.

A semi-automated method for determination of glycosylation of plasma proteins using the thiobarbituric acid method is described. Plasma samples (100 microL) and a plasma pool used as a secondary standard were incubated in 0.3 M oxalic acid at 100 degrees C for exactly 2 h. The hydroxymethyl furfural released and the total protein were measured concurrently on a Technicon AAII Autoanalyzer. Addition of 10 or 20 mmol glucose to plasma samples caused a minimal increase in the measured glycosylated protein. Within-batch and between-batch coefficients of variation were 3.1% and 4.9% respectively. The mean glycosylated protein levels for 52 normals and 48 maturity-onset diabetics were (+/- 1SD) 0.96 +/- 0.13 and 1.75 +/- 0.32 nmol HMF/mg protein/2 h incubation.

Autoanalysis↗

Recovery potentials following CNS lesions: a brief historical perspective in relation to modern research data on neuroplasticity.

This article begins with a brief historical account of our attempts to understand the brain by endlessly mapping out discrete structural and functional territories. These territorial or classical maps are then contrasted with the new metabolic maps, which show brain function and plasticity as it has never been conceptualized or visualized before. The new maps, along with more recent research in such areas as neuroplasticity, synaptogenesis, parallel processing, holistic brain functioning, sexual dimorphism, and individual differences, are giving our profession a solid scientific foundation on which to base many of the rehabilitation techniques used today in pediatrics, geriatrics, psychiatry, and physical disabilities.

Brain↗

Rapid symptomatic relief of streptococcal pharyngitis in children.

Sixty 3- to 14-year-old outpatients with positive streptococcal group A bacterial cultures and clinical signs and symptoms of pharyngitis were treated with a single intramuscular (IM) injection of penicillin G benzathine/penicillin G procaine in a multicenter study. At the first follow-up visit, usually within 48 hours of the injection, 60 children had negative cultures, and the mean body temperature had decreased from 100.2 +/- 1.6 degrees F to 98.5 +/- 0.5 degree F (P less than 0.05). At this time, the investigators rated 77% of the children clinically cured and the remaining 23% improved; major signs and symptoms (sore throat, difficulty swallowing, lethargy, and cervical node enlargement and tenderness) had disappeared in nearly all of the children. Initial injection site pain, noted in only 15% of the children 48 hours later, probably was secondary to the injection and not drug related. Most other adverse reactions (in seven children) also were injection related, were mild or moderate, and required no countermeasures. At the second follow-up visit approximately 10 days after injection, all children were considered clinically and bacteriologically cured. Thus, the combination of IM benzathine and procaine penicillin not only is safe and effective but eliminates compliance concerns.

Adolescent↗

A new early life-stage toxicity test using the California grunion (Leuresthes tenuis) and results with chlorpyrifos.

California grunion were continuously exposed as embryos and fry to technical chlorpyrifos in two toxicity tests conducted in the same exposure apparatus. The first test, a 35-day early life-stage (ELS) test, began with approximately 2.5-day-old embryos that were exposed in flow-through aquaria in darkness until hatching was stimulated on Day 9 of exposure. The second toxicity test, a fry test, began with newly hatched fry and lasted 26 days. Test water temperature ranged from 23 to 26 degrees C and salinity from 24.5 to 34.0%. Results of the two tests were similar, indicating that exposure of embryos added little to the overall toxicity of chlorpyrifos to grunions. Percentage hatch of embryos was unaffected by the chlorpyrifos concentrations tested. Fry survival was apparently reduced in nominal concentrations greater than or equal to 1.0 micrograms/liter in both tests, but significantly so in concentrations greater than or equal to 1.0 micrograms/liter in the ELS test and greater than or equal to 2.0 micrograms/liter in the fry test. When compared with carrier controls, mean fish weights were significantly reduced in nominal chlorpyrifos concentrations greater than or equal to 0.5 micrograms/liter in the ELS test and greater than or equal to 1.0 micrograms/liter in the fry exposure. Mean bioconcentration factors were 770X for fish that survived the ELS test and 190X for those that survived the fry test. Results demonstrate the practicality of conducting ELS tests for the first time with a marine fish from the Pacific coastal waters of the United States.

Animals↗

Relative sensitivity of six estuarine fishes to carbophenothion, chlorpyrifos, and fenvalerate.

The acute toxicity (96-hr LC50) of carbophenothion, chlorpyrifos, and fenvalerate to six estuarine fishes was determined in flow-through laboratory tests. The atherinid fishes (Menidia menidia, M. peninsulae, M. beryllina, and Leuresthes tenuis) consistently were among the most sensitive species tested and were similar to each other in their sensitivity to pesticides. The sensitivity of sheepshead minnows (Cyprinodon variegatus) to carbophenothion was the same as that of the atherinids. For fenvalerate, the sheepshead minnow LC50 was an order of magnitude greater than that of the most sensitive atherinid, whereas the LC50 for chlorpyrifos and sheepshead minnows was two orders of magnitude greater. Gulf toadfish (Opsanus beta) were the least sensitive fish tested with carbophenothion and chlorpyrifos and their 96-hr LC50 for fenvalerate ranked between the LC50 for sheepshead minnows and atherinids. Test results were compared to acute toxicity data for other estuarine fishes and invertebrates.

Animals↗

Adherence of Candida to cultured vascular endothelial cells: mechanisms of attachment and endothelial cell penetration.

To elucidate the pathogenesis of hematogenous Candida infections, we developed an in vitro model of Candida adherence to and penetration of human endothelial cells. We enhanced or inhibited adherence in order to probe mechanisms of attachment. Adherence of Candida albicans showed a linear relation to Candida inoculum (range, 10(2)-10(5) cfu, r = .99, P less than .01) and exceeded that of less virulent Candida species and that of Saccharomyces cerevisiae (P less than .01). Candida immune serum blocked attachment (greater than 95% inhibition; P less than .001), however, this activity was abolished by immunoprecipitation of immune serum with C. albicans mannan (P less than .001) and was unaffected by immunoprecipitation with S. cerevisiae mannan or by adsorption with particulate chitin. Adherence was diminished by exposing C. albicans to heat (greater than 99% inhibition; P less than .01), UV light (98% inhibition; P less than .01), or sodium periodate (greater than 72% inhibition; P less than .01). An extract from heat-exposed C. albicans blocked adherence (greater than 51% inhibition; P less than .001). Transmission electron microscopy demonstrated that viable or killed Candida organisms were attached to endothelial cells, were enveloped by membrane processes from the endothelial cell surface, and were incorporated into the endothelial cells within phagosomes. Cytochalasin B blocked incorporation without blocking surface attachment.

Adhesiveness↗

Loss of diabetic control and increased protein glycosylation following minor intercurrent infections.

To investigate the effect of intercurrent infections, 30 insulin-dependent diabetics and 12 normal subjects were followed prospectively during one winter, with short-term periods of control being assessed by the degree of glycosylation of plasma proteins. Eight diabetics and 7 normal subjects developed an intercurrent infection. During stable control, the diabetics had a mean +/- 1 S.D. glycosylation of 0.90 +/- 0.06 nmol HMF/mg protein/2 hour incubation, compared with the normal subjects of 0.63 +/- 0.04 nmol HMF/mg protein/2 hour. Following infection, there was no increase in glycosylated plasma protein in the normal subjects, but the diabetics increased at 3 and 6 days to 1.07 +/- 0.17 and 1.12 +/- 0.17 nmol HMF/mg protein/2 hour respectively (p less than 0.05 and p less than 0.01). This was similar to levels (1.09 +/- 0.20 nmol HMF/mg protein/2 hour) found in 12 diabetic subjects admitted to hospital because of marked loss of control with ketonuria. The marked protein glycosylation effect of temporary loss of glucose control following 'minor' intercurrent infections suggests that more attention should be paid to diabetic control during brief illnesses.

Adult↗

Patient-orientated metered capillary blood collection.

A small collector bottle, with a precision-moulded top, allows capillary blood from a finger-prick to be automatically metered into a diluent for subsequent laboratory analysis. This device, which has been successfully used by patients to obtain full blood counts, glycosylated haemoglobin values and blood glucose measurements, may have wide application.

Blood Cell Count↗

Plasma fibronectin, factor VIII-related antigen and fibrinogen concentrations, and diabetic retinopathy.

Fibronectin and factor VIII-related antigen (VIIIR: AG), which are produced by the endothelium and are involved in cellular adhesion, may have a role in the development of diabetic retinopathy. We have measured plasma levels of these glycoproteins and of fibrinogen in 9 control males, 10 insulin-dependent diabetic males with nil or minimal retinopathy and 10 insulin-dependent diabetic males with proliferative retinopathy. These three groups were closely matched for age, body weight and smoking habit. The diabetics in each retinopathy group had similar duration of disease and insulin doses. There was no significant difference between plasma fibronectin concentrations in the three groups. Both plasma factor VIII-related antigen activity and fibrinogen concentration were higher amongst the diabetic subjects, especially those with proliferative retinopathy. These two latter measures correlated significantly when the diabetics were considered as a single group, whereas they did not correlate with fibronectin. Plasma concentrations of fibrinogen and factor VIII R: AG, but not fibronectin, have an association with diabetic microvascular disease.

Adult↗