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Biomedical subjects

M Cunningham

Publications and source records attributed to M Cunningham.

35 records · Page 2Linked to original sources
PubMed1990

Counselling survivors of torture and refugee trauma.

A substantial number of refugees arriving in Australia are the victims of torture and other forms of organised violence. In this article, the authors provide an overview of the broad range of physical and emotional disabilities that arise from these experiences, examine the special difficulties in identifying and assessing patients at the primary health care level, and offer an approach to counselling for survivors and their families.

Counseling↗
PubMed1988

Fragile X syndrome and acute lymphoblastic leukemia.

Fragile X [Fra(X)] syndrome is an example of a heritable fragility syndrome associated with mental retardation. It is characterized by a fragile site on the X chromosome at Xq27-28. There have recently been three reports of malignant solid tumors associated with Fra(X) syndrome. We describe the first case of a hematologic malignancy [T-cell acute lymphocytic leukemia (ALL)] in a patient with Fra(X) syndrome. The possibility of a predisposition to malignancy in Fra(X) is discussed.

Child, Preschool↗
PubMed1988

Reduced thiols and the effect of intravenous nitroglycerin on platelet aggregation.

Nitroglycerin inhibits platelet aggregation in vitro and this effect may be important in its overall mechanism of action. In addition, its use has been associated with prolonged bleeding times and hemorrhagic complications. Despite these experimental and clinical observations, no significant antiplatelet effect of nitroglycerin has been observed ex vivo during intravenous nitroglycerin administration to patients. Because the in vitro antiplatelet effects of nitroglycerin have been shown by one of the investigators participating in this study to depend on the presence of sufficient stores of reduced intracellular thiol--which are readily depleted ex vivo by nitroglycerin in the formation of S-nitrosothiols--an attempt was made to unmask nitroglycerin-mediated inhibition of platelet aggregation by exposing platelets taken from patients treated with nitroglycerin to the reduced thiol N-acetylcysteine ex vivo. The obtained data demonstrate that platelets taken from patients treated with intravenous nitroglycerin manifest attenuated aggregation responses ex vivo when thiol stores are repleted. It is therefore proposed that the mechanism of action of nitroglycerin is mediated in part by its antiplatelet effect and that this effect depends on the adequacy of reduced intracellular thiol stores.

Acetylcysteine↗
PubMed1986

Cytomegalovirus primo-infection in a patient with idiopathic proctitis.

A young heterosexual man, suffering from a low-grade, idiopathic proctitis, who developed severe rectal ulcerations at the time of a primary cytomegalovirus (CMV) infection is described. CMV was cultured from the rectum on two occasions. Sero-conversion and the appearance of a specific IgM antibody response to CMV were documented, suggesting that this was a case of a primo-infection by CMV, and not one of reactivation of latent CMV infection.

Adult↗
PubMed1985

Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation.

Platelet activation is accompanied by the appearance on the platelet surface of approximately 45,000 receptor sites for fibrinogen. The binding of fibrinogen to these receptors is required for platelet aggregation. Although it is established that the fibrinogen receptor is localized to a heterodimer complex of the membrane glycoproteins, IIb and IIIa, little is known about the changes in this complex during platelet activation that result in the expression of the receptor. In the present studies, we have developed and characterized a murine monoclonal anti-platelet antibody, designated PAC-1, that binds to activated platelets, but not to unstimulated platelets. PAC-1 is a pentameric IgM that binds to agonist-stimulated platelets with an apparent Kd of 5 nM. Binding to platelets is dependent on extracellular Ca2+ (KCa = 0.4 microM) but is not dependent on platelet secretion. Platelets stimulated with ADP or epinephrine bind 10,000-15,000 125I-PAC-1 molecules/platelet while platelets stimulated with thrombin bind 20,000-25,000 molecules/platelet. Several lines of evidence indicate that PAC-1 is specific for the glycoprotein IIb.IIIa complex. First, PAC-1 binds specifically to the IIb.IIIa complex on Western blots. Second, PAC-1 does not bind to thrombasthenic platelets or to platelets preincubated with ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid at 37 degrees C, both of which lack the intact IIb.IIIa complex. Third, PAC-1 competitively inhibits the binding of 125I-A2A9, and IgG monoclonal antibody that is specific for the IIb.IIIa complex. Fourth, the antibody inhibits fibrinogen-mediated platelet aggregation. These data demonstrate that PAC-1 recognizes an epitope on the IIb.IIIa complex that is located near the platelet fibrinogen receptor. Platelet activation appears to cause a Ca2+-dependent change involving the glycoprotein IIb.IIIa complex that exposes the fibrinogen receptor and, at the same time, the epitope for PAC-1.

Antibodies, Monoclonal↗
PubMed1985

Kinetic analysis of various heparin fractions and heparin substitutes in the thrombin inhibition reaction.

Kinetic characteristics of several heparin preparations and substitute heparins were determined to help understand the bases for activity differences. Several materials were highly active in factor Xa inhibition and the reaction rate at constant factor Xa concentration appeared to be predicted by the extent of intrinsic antithrombin III fluorescence change induced by the polysaccharide. Heparin fractions of different molecular weight and affinity for antithrombin III showed similar kinetic parameters in catalysis of the thrombin-antithrombin III reaction when these parameters were expressed on the basis of antithrombin III-binding heparin. The latter was determined by stoichiometric titration of the antithrombin III fluorescence change by the heparin preparation. However, the various heparin fractions showed very different specific activities per mg of total polysaccharide. This indicated that functional heparin molecules had similar kinetic properties regardless of size or antithrombin III-binding affinity and is possible because the Km for antithrombin III is determined by diffusion rather than by binding affinity. Substitute heparins and depolymerized heparin were poor catalysts for thrombin inhibition, due at least partially to their affinity for thrombin. This latter binary interaction inhibits thrombin reaction in the heparin-catalyzed reaction.

Animals↗
PubMed1978

Werdnig-Hoffmann disease. The effects of intrauterine onset on lung growth.

Thoracic gas volume (TGV), resting lung volume at end expiration, was measured by the plethysmographic technique in 9 infants with Werdnig-Hoffmann disease. Five of these infants were considered to have intrauterine onset of the disease; the mother in each case had reported a pronounced reduction in fetal activity during the last trimester of pregnancy, and 4 were found to be hypotonic at birth. The remaining 4 infants appeared normal at birth and did not develop any signs of the disease until between 2 and 12 weeks postnatally. Those with intrauterine onset of disease had a significantly reduced TGV (mean 20.8 ml kg(-1)), whereas those with postnatal onset had normal lung volumes (means 36.1 ml kg(-1)). The reduction in lung volume correlated only with intrauterine onset of disease, and was not related to either the degree of muscle weakness or the duration of disease. There is increasing evidence that fetal breathing movements may be one of the essential prerequisites for normal fetal lung development. It is therefore possible that diminished fetal breathing movements, resulting from weakness of the respiratory musculature in utero, could be responsible for the reduction in lung volume found in those infants with intrauterine onset of the disease.

Humans↗
PubMed1978

Cockayne's syndrome and emphysema.

A 5-year-old boy with Cockayne's syndrome is described. In addition to the recognised clinical features, he presented with severe fixed airways obstruction, and investigations confirmed clinical and physiological emphysema. In a disorder associated with many of the features of aging, it is probably that the presence of relative alpha-1-antitrypsin deficiency (1.5 g/l) in a child with PiMZ phenotype, contributed to his severe lung disease.

Airway Obstruction↗
PubMed1976

Purification and properties of cathepsin D from porcine spleen.

Cathepsin D was purified from porcine spleen to near homogeneity as determined by gel electrophoresis. The isolation scheme involved an acid precipitation of tissue extract, DEAE-cellulose and Sephadex G-200 chromatography, and isoelectric focusing. The end product represented about a 1000-fold purification and about a 10% recovery. The purified enzyme was the major isoenzyme, which represented 60% of cathepsin D present in porcine spleen. Two minor isoenzymes of cathepsin D were present in small amounts. The purified enzyme resembled porcine pepsin in molecular weight (35,000), amino acid composition, and inactivation by specific pepsin inactivators. The pH activity curve of the purified enzyme showed two optima near pH 3 and 4. The relative activities at these optimal pH values were affected by salt concentration. Experimental evidence indicated that the two-optima phenomenon is a property of a single enzyme species.

Amino Acid Sequence↗
PubMed1975

Immunochemical properties of streptococcal M protein purified by isoelectric focusing.

Electrofucusing of an alkaline extract of type 24 streptococcal M protein yielded an antigenic fraction that was type specific and apparently homogeneous. The haptenic nature of this fraction was suggested by its inability to precipitate type-specific antiserum or to induce opsonic antibodies in rabbits, despite its ability to strongly inhibit opsonization of homologous-type streptococci by M antibody. The fraction migrated as a single band upon electrophoresis in sodium dodecyl sulfate (SDS) acrylamide gel. The mobility of the protein band was consistent with a molecular weight of 36,500 daltons. In some experiments using larger quantities of protein, a second faint protein band with an average molecular weight of 70,000 was observed, suggesting the presence of dimers of the 36,500-dalton protein. Amino acid analysis showed the predominant amino acid to be glycine followed by aspartic acid and glutamic acid. Moreover, this M protein fraction was free of non-type-specific immunotoxic properties in guinea pigs and in man. Although apparently not immunogenic, this nontoxic fraction may provide a useful tool to study the relationship of the type-specific protective moiety to potentially harmful "impurities" in M protein vaccines.

Amino Acids↗
PubMedDate not supplied

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Aged↗