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Biomedical subjects

M McGill

Publications and source records attributed to M McGill.

At least 19 recordsLinked to original sources
PubMed1992

Expression of TTK, a novel human protein kinase, is associated with cell proliferation.

We have isolated the full-length sequence for a unique human kinase, designated TTK. TTK was initially identified by screening of a T cell expression library with anti-phosphotyrosine antibodies. The kinases most closely related to TTK are the SPK1 serine, threonine and tyrosine kinase, the Pim1, PBS2, and CDC2 serine/threonine kinases, and the TIK kinase which was also identified through screening of an expression library with anti-phosphotyrosine antibodies. However, the relationships are distant with less than 25% identity. Nevertheless, TTK is highly conserved throughout phylogeny with hybridizing sequences being detected in mammals, fish, and yeast. TTK mRNA is present at relatively high levels in testis and thymus, tissues which contain a large number of proliferating cells, but is not detected in most other benign tissues. Freshly isolated cells from most malignant tumors assessed expressed TTK mRNA. As well, all rapidly proliferating cell lines tested expressed TTK mRNA. Escherichia coli expressing the complete kinase domain of TTK contain markedly elevated levels of phosphoserine and phosphothreonine as well as slightly increased levels of phosphotyrosine. Taken together, these findings suggest that expression of TTK, a previously unidentified member of the family of kinases which can phosphorylate serine, threonine, and tyrosine hydroxyamino acids, is associated with cell proliferation.

Amino Acid Sequence↗
PubMed1992

The distribution of immunoreactive interferon-gamma-containing cells in normal human tissues.

An immunohistochemical technique has been used to study the distribution of lymphocytes expressing interferon-gamma in normal adult tissues. The greatest concentrations of these cells were seen in mucosal sites exposed to a resident microflora. It is proposed that such organisms, by eliciting immune responses, provide the stimulus for the production of 'physiological' interferon-gamma. This in turn may act to preserve the 'tone' or readiness of the immune system.

Adult↗
PubMed1991

Insulitis in type 1 (insulin-dependent) diabetes mellitus in man--macrophages, lymphocytes, and interferon-gamma containing cells.

This study sought to determine, firstly, the relative frequency of lymphocytes and macrophages and, secondly, the percentage of lymphocytes containing interferon-gamma in inflamed islets (insulitis) of patients with type 1 (insulin-dependent) diabetes. Autopsy pancreases of 12 patients who had died of recent-onset type 1 diabetes and one pre-diabetic patient who had died of cardiomyopathy were examined immunohistochemically. In the 87 islets that were studied, the lymphocyte macrophage ratio was 9.7:1 and approximately 40 per cent of the lymphocytes contained interferon-gamma. Interferon-gamma release in the insulitis process may be involved in the pathogenesis of type 1 diabetes.

Adolescent↗
PubMed1991

Determinants of blood and body fluid exposure in a large teaching hospital: hazards of the intermittent intravenous procedure.

Determinants of staff exposure to blood and body fluids in a 1100-bed hospital were examined over a 2-year period. Eighty-two percent of the 799 reported accidental exposures were needlestick injuries, and 18% were cutaneous or mucous membrane splashes. Nurses and nursing students incurred 78.8% of the exposures; respiratory technologists and laboratory personnel, 9.2%; medical personnel, 7.5%; and support staff, 4.2%. Rate of exposure per 100,000 hours worked showed nursing students to be at particularly high risk, highlighting the need for specific instruction. Analysis of events leading to needlestick-related exposures revealed that the heparin lock intermittent intravenous procedure was involved in 26%; recapping accounted for 17%; improper disposal, 15%; manipulating equipment, 14%; phlebotomy, 12%; and other needlestick events, 16%. Ocular splashes and spills onto nonintact skin each accounted for 50% of the total number of non-needlestick-related exposures. This study revealed the hazardous nature of the intermittent intravenous procedure, prompting specific revisions in this procedure as well as promoting point-of-use sharps disposal and other preventive measures.

Accident Prevention↗
PubMed1990

Interleukin 2-induced tyrosine phosphorylation. Interleukin 2 receptor beta is tyrosine phosphorylated.

Interaction of interleukin 2 (IL2) with its high affinity membrane receptor complex (IL2R) is sufficient to induce proliferation of T lymphocytes. However, the biochemical mechanisms by which IL2 induces this process remain unresolved. The IL2R complex consists of at least two distinct polypeptides that bind IL2, a 75-kDa intermediate affinity subunit (IL2R beta) and a 55-kDa low affinity subunit (IL2R alpha). As indicated by Western blotting with anti-phosphotyrosine-specific antibodies and confirmed by phosphoamino acid analysis, we now demonstrate that interaction of the T cell growth factor interleukin 2 (IL2) with its high affinity receptor on IL2-sensitive human peripheral blood lymphoblasts induces tyrosine phosphorylation of proteins of 92, 80, 78, 70-75, and 57 kDa. IL2 induced tyrosine phosphorylation in YT 2C2 cells which express only the 75-kDa intermediate affinity IL2 binding molecule (IL2R beta) but not in cells which either express only the 55-kDa low affinity IL2 receptor molecule (IL2R alpha) or no IL2-binding sites. Therefore, IL2R beta, in the absence of IL2R alpha, appears sufficient to transduce the transmembrane signal leading to tyrosine phosphorylation. Two different antibodies reactive with phosphotyrosine specifically immunoprecipitated IL2R beta cross-linked to radiolabeled IL2. These findings suggest that IL2R beta is a substrate for the tyrosine kinase which is activated by IL2 binding to its receptor. Thus, like several other growth factor receptors, activation of the IL2R results in an increase in tyrosine phosphorylation with the receptor itself serving as one substrate.

Amino Acids↗
PubMed1990

Interrelationship between signals transduced by phytohemagglutinin and interleukin 1.

In the murine cell line LBRM-331A5, phytohemagglutinin (PHA) induces secretion of the T cell growth factor interleukin 2 (IL2). IL1 augments PHA-induced IL2 production. In this cell line, PHA stimulates a number of biochemical changes including phospholipid hydrolysis, increases in cytosolic free calcium [( Ca2+]i), membrane hyperpolarization, cytosolic alkalinization, and tyrosine phosphorylation of specific substrates. Using LBRM cells, we have studied the interrelationship between these events and the secretion of IL2. Increases in [Ca2+]i triggered by PHA or following addition of ionomycin result in membrane hyperpolarization but are not required for PHA-induced cytosolic alkalinization or tyrosine phosphorylation. Addition of IL1 to PHA-stimulated cells did not affect any of the biochemical parameters, although it significantly augmented PHA-induced IL2 secretion. Increasing [Ca2+]i with ionomycin did not trigger IL2 secretion, increases in cytosolic pH, or tyrosine phosphorylation in the presence or absence of IL1. Preventing increases in cytosolic pH did not alter PHA-induced changes in [Ca2+]i or membrane potential. These data are compatible with PHA including activation of phospholipase C and production of inositol phosphates resulting in both release of Ca2+ from internal stores and transmembrane uptake of Ca2+ as well as activation of protein kinase C. However, unlike other growth factor or mitogen-stimulated systems, the changes stimulated by PHA and IL1 in LBRM cells including IL2 secretion are not regulated by a pertussis toxin-sensitive G protein.

Adenosine Diphosphate Ribose↗
PubMed1990

A search for the presence of the enteroviral capsid protein VP1 in pancreases of patients with type 1 (insulin-dependent) diabetes and pancreases and hearts of infants who died of coxsackieviral myocarditis.

Using an antiserum raised to a recombinant coxsackie virus B 3 capsid protein, VP1, an immunocytochemical technique was developed which was capable of detecting the presence of all coxsackie B viruses in formalin fixed paraffin embedded infected tissue culture cells. This technique was tested on autopsy heart and pancreas from 21 patients who were thought to have died of acute coxsackievirus B myocarditis. Cardiac myocytes were positive for the VP1 protein in 12 of 20 cases where the heart was available for study. Insulitis was present in the pancreas in seven of these cases and in all seven islet endocrine cells containing VP1 were found. VP1 was only rarely found in exocrine pancreas. In heart and pancreas, cells shown to contain VP1 usually showed signs of necrosis. Autopsy pancreases from 88 patients who had died at clinical presentation of Type 1 (insulin-dependent) diabetes mellitus showed no evidence of the presence of VP1. The continuing destruction of insulin-secreting B cells seen at the time of death in the diabetic pancreas is unlikely to be due to a direct cytopathic effect of a coxsackie B virus. However, this study does not exclude the possibility that a persistent infection of B cells by a defective enterovirus may result in their destruction by an autoimmune mechanism.

Acute Disease↗
PubMed1990

Abnormalities of ascorbic acid metabolism and diabetic control: differences between diabetic patients and diabetic rats.

Ascorbic acid is required in the synthesis of collagen and is also an important anti-oxidant. In a previous study, plasma ascorbic acid concentration was found to be decreased in diabetic patients but there was no relationship with blood glucose level. In the current study of diabetic patients, both plasma ascorbic acid and its urinary excretion correlated inversely with glycosylated hemoglobin level. Plasma ascorbic acid was also lower in diabetic rats but urinary ascorbic acid was elevated. The divergent trend in urinary ascorbic acid excretion observed in diabetic patients and diabetic rats may be due to difference in the ability of these two species to synthesize ascorbic acid. Difference in renal reabsorption of ascorbic acid may also be a relevant factor. The lower plasma and urinary ascorbic acid levels in diabetic patients with more severe hyperglycaemia indicates that this group of patients is particularly at risk of developing deficiency of this vitamin. As ascorbic acid has many important functions in the body, it may be necessary to supplement this vitamin in patients with chronically poorly controlled diabetes.

Adult↗
PubMed1989

Anti-smoking programme for diabetic patients: the agony and the ecstasy.

It is generally accepted that people with diabetes should be encouraged to abstain from smoking but there are few data on the best strategy to implement this. In a preliminary survey of our diabetic patients, knowledge of the general and specific health effects of smoking was poor. In a prospective study of 70 diabetic smokers, only 50% agreed to participate in an anti-smoking programme, and the drop-out rate was high irrespective of whether the content of the programme was general or specific for diabetes. The enrollment rate was best 2 months after the diagnosis of diabetes and the drop-out rate was highest in patients recruited immediately following diagnosis. According to self-reported data, cigarette consumption fell after the first session of the anti-smoking programme but this could not be verified by the measurement of plasma cotinine. It is concluded that an anti-smoking counselling programme based on provision of information, within the context of a specialized diabetes centre, is not cost-effective.

Cotinine↗
PubMed1988

Red blood cell membrane microviscosity correlates with posttransfusion survival.

The cholesterol/phospholipid and sphingomyelin/phospholipid ratios of red blood cells stored for 42 days were unchanged after storage. However, the total phospholipid concentration in the red cells decreased suggesting a loss of red cell membrane during storage. The 24 h survival of the stored red cells was assessed by the Cr technique in homologous donors. A decrease in fluorescence polarization of diphenylhexatriene incorporated into the membrane was observed following storage which correlated with survival. Thus, molecular defects in the lipid bilayer are associated with long-term storage of red blood cells.

Blood Preservation↗
PubMed1988

The effects of argon laser on in vitro aggregation of platelets in platelet rich plasma and whole blood.

The effects of an Argon laser on platelet aggregation were studied, since platelets may be exposed to laser energy when used intravascularly. Various preparations of platelets in platelet rich plasma (PRP) and whole blood, with or without aspirin, were tested with the aggregating agents ADP, collagen, thrombin, and epinephrine. Simultaneous release of ATP was also measured in PRP. At relatively low levels of irradiation, platelet aggregation was potentiated. Enhancement was evidenced by an increase in percent aggregation, earlier onset of the reaction, and reduction in the amount of aggregating agent required. In PRP, the mechanism of laser potentiation appeared to be the release of endogenous ATP from platelets. At relatively high levels of irradiation, platelets were destroyed and aggregation abolished. In whole blood, the mechanism was somewhat more complicated since release of ATP occurred from RBCs as well as platelets. Spontaneous aggregation following laser treatment occurred in isolated instances in PRP and in every trial in whole blood preparations. Aspirin ingestion inhibited the laser's effects in PRP but not in whole blood. These results may have important clinical implications for laser angioplasty, and the potentiated aggregation response may prove useful in laboratory studies of platelet function.

Adenosine Triphosphate↗
PubMed1988

A putative new growth factor in ascitic fluid from ovarian cancer patients: identification, characterization, and mechanism of action.

Ascitic fluid form ovarian cancer patients (n = 16), but not from patients with other cancers or with benign diseases, contains a growth-promoting activity which induces the proliferation of both fresh ovarian cancer cells (n = 5) and the ovarian cancer cell line HEY. The ascitic fluid growth factor(s) appears to signal cells through binding and activation of specific, saturable, high-affinity cell surface receptors. Incubation of fresh or cultured ovarian cancer cells with a partially purified preparation of ascitic fluid stimulates phosphatidylinositol turnover and increases cytosolic-free calcium. Each of these biochemical events has been implicated in the action of growth factors. Purified preparations of previously identified growth factors including epidermal growth factor, transforming growth factor-beta, tumor necrosis factor, platelet-derived growth factor, thrombin, insulin, interleukin-1, interleukin-2, vasopressin, angiotensin, alpha- and gamma-interferons, and fibroblast growth factor did not increase cytosolic-free calcium in either fresh ovarian cancer cells or HEY cells. Therefore, ascitic fluid appears to contain one or more previously unidentified growth factors which activate ovarian cancer cells through phosphatidylinositol hydrolysis and resultant changes in cytosolic-free calcium.

Ascitic Fluid↗
PubMed1987

Evaluation of a new microporous filtration membrane system for therapeutic plasma exchange.

A new therapeutic plasma exchange device developed by Sarns Inc./3M was evaluated in plasmapheresis of 20 healthy volunteers and in a multicenter clinical study of therapeutic plasma exchange that included 49 patients. Safety and efficacy of plasma separation from whole blood were assessed for a module that contains Durapore microporous surfactant-free polyvinylidene fluoride membrane (Millipore Corp., Bedford, Mass., USA). The extra-corporeal volume was 80 ml. Citrate and heparin anticoagulants were utilized. Mean plasma separation efficiency was 62% with unhindered passage of plasma proteins through the membrane pores and no hemolysis or activation of complement as measured by total hemolytic complement (CH50) and C3 conversion. Mean decrease in platelet count after procedures was 10%. No severe reactions occurred, and citrate effects (13%) were comparable to values reported with centrifugal instruments. The Sarns Inc./3M Therapore device is a rapid, safe and efficient system for plasma exchange and potentially for source plasma collection. The principal benefits are small extracorporeal volume and cell-free filtrate.

Citrates↗
PubMed1987

Platelet membrane vesicles reduced microvascular bleeding times in thrombocytopenic rabbits.

We investigated the possible role of platelet membrane vesicles on hemostatic function in vivo. Platelet membrane vesicles were prepared from rabbit platelets stored for up to 6 months at -65 degrees C and transfused into thrombocytopenic rabbits. Significant reductions in microvascular bleeding times were observed up to 24 hours after transfusion, with the greatest corrections at 4 hours. Measurements of factor V, factor VIII, fibrin degradation products, and fibrinogen in animals transfused with membrane ruled out intravascular coagulation and suggested a direct effect of platelet membrane vesicles at the bleeding sites. This conclusion was supported morphologically by identification of membrane vesicles in bleeding time lesions and radiologically by accumulation of 111In-labeled vesicles in lesions. Production of platelet membrane vesicles was simple, and freezing allowed long-term storage of a product capable of short-term hemostasis.

Animals↗
PubMed1979

Effects of storage on platelet reactivity to arterial subendothelium during blood flow.

The usual in vitro methods for studies of platelets after storage do not measure physiological parameters such as capability for interaction with vessel wall subendothelium during blood flow conditions. For studies reported here we adapted a technique described by Baumgartner (Microvasc Res 5:167, 1973) to quantitate platelet interactions with subendothelium during blood flow and before and after storage at 4 degrees and 22 degrees and by a modified 4 degrees procedure called temperature cycling. The results indicated that platelets kept at 22 degrees for 72 hr interacted with subendothelium in quantities which were less than 10% that of fresh controls. However, storage at 4 degrees and by temperature cycling produced interactions equal to 71% and 42% of controls, respectively. The data also indicated that utilization of Baumgartner's technigue as described here will (1) provide an in vitro technique for identification of qualitative defects responsible for the delayed hemostatic effectiveness of 22 degrees-stored platelets and (2) permit an objective and quantitative analysis of prospective improvements in storage before in vivo function testing is necessary.

Animals↗