Biomedical subjects
Publications and source records attributed to A Cheung.
The activity of the rat liver vitamin K-dependent gamma-glutamyl carboxylase has been shown to be stimulated by the presence of the free amino terminal 'propeptide' region of the primary gene product of its normal protein substrates. A series of analogs of the human factor X propeptide have been utilized to demonstrate the structure/function relationships important in these interactions.
Primary dissecting aneurysm of the coronary arteries usually presents as sudden death or complications of myocardial infarction. The most common site of the dissection has been the anterior descending branch of the left coronary artery. A Chinese woman with primary dissecting aneurysm of the right coronary artery presenting as cardiac tamponade is reported. This is the first case of ruptured coronary aneurysm reported in the Chinese and the only case presenting as cardiac tamponade since 1931.
Routine cytological examination and HPV-DNA probing were performed on cervical cells obtained from 215 pregnant Chinese females. The procedure utilized the specific binding of a mixture of complementary [32P]-labelled RNA probes to membrane-bound target HPV DNA types 6, 11, 16, 18, 31, 33 and 35. Positive results for HPV-DNA were obtained in 11/215 (5%) of the cases. The cervical smears were routinely processed and in 3/215 (1.5%) cases a cytological diagnosis of wart virus infection was made. All three were included in the 11 probe-positive cases. Using similar molecular biological techniques, pregnant Western females have an incidence of HPV infection of the cervix which is up to five times that of the present series. This is an unexpected finding in view of the fact that the incidence of cervical cancer is higher in Chinese women than American women.
Infection of mural thrombus over an area of old myocardial infarct was found in an elderly woman with cholangitis. This case is unique since cholangitis was thought to be the cause of septicaemia and ventricular aneurysm was not present.
The prenatal identification of various types of placentation is important for the antenatal management of twin pregnancies. Such classification can be achieved with the use of ultrasound examination. In 32 cases of twin pregnancy the intervening septum was classified as either a thick (dichorionic) or thin (monochorionic) type. Macroscopic and microscopic examination of the placenta after delivery confirmed the ultrasound diagnosis in 24 of the 30 cases, an accuracy of 80%.
A prospective, observational study of forty pre-eclamptic patients was conducted to confirm or refute reports of a platelet functional defect superimposed on the consumptive thrombocytopenia of pre-eclampsia. Investigations included a platelet count, in vivo platelet function as assessed by a Duke bleeding time, and in vitro platelet function as assessed by thromboxane B2 and Platelet Factor 3 (PF 3). The overall incidence of thrombocytopenia was 15%. Prolonged bleeding time and slightly decreased availability of PF 3 (evidence of possible platelet dysfunction) was present in 2.5% of patients while 21% had evidence of fibrinolysis with an elevated monoclonal D-dimer. In the assessment of suitability for regional blockade, a platelet count is essential. If the platelet count is between 50 and 100 x 10(9)/l a bleeding time is indicated.
The liver microsomal vitamin K-dependent carboxylase catalyzes the post-translational conversion of specific glutamyl to gamma-carboxyglutamyl (Gla) residues in precursor forms of a limited number of proteins. These proteins contain an amino-terminal extension (propeptide) that is presumed to serve as an enzyme recognition site to assure their normal processing. The free, noncovalently bound propeptide has also been shown to stimulate the in vitro activity of this enzyme. This peptide has now been shown to lower the app Km of a low-molecular-weight Glu site substrate while having no influence on the app Km of the other substrates, vitamin KH2, O2, and CO2/HCO3-. Propeptide addition was shown to have no influence on the ratio of the two products of the enzyme, Gla and vitamin K-2,3-epoxide. Stimulation of carboxylase activity by the propeptide from human factor X was observed in a number of rat tissues and in the liver of a number of different species. Stability of the enzyme in crude microsomal preparations was greatly enhanced by the presence of propeptide. These observations are consistent with the hypothesis that this region of the protein substrates for the carboxylase not only serves an enzyme recognition or docking function but also modulates the activity of the enzyme by altering the affinity for one of its substrates.
The effects of recombinant DNA-derived chicken growth hormone (rcGH) on plasma corticosterone in young broiler cockerels were investigated. A single injection of 200 micrograms/kg rcGH significantly increased plasma corticosterone concentrations 2 hr (but not 20 or 40 min) after treatment. Administration of 10 or 100 micrograms/kg rcGH also significantly increased plasma corticosterone levels after 2 hr, with the higher dose eliciting greater responses. Chronic treatment with seven daily injections of the same doses of rcGH gave similar increases in plasma concentrations of corticosterone. No obvious difference in magnitude of plasma corticosterone was observed between acute and chronic exposure to rcGH. In a further experiment in which serial blood sampling was performed after a single injection or five daily injections of vehicle or 200 micrograms/kg rcGH, there were significant increases in plasma corticosterone concentrations 40 min after acute rcGH treatment and 40 and 80 min after chronic treatment when compared with plasma corticosterone concentrations of vehicle-injected controls. However, the increases could have incorporated a stress response due to repeated sampling because the control birds also showed elevated plasma corticosterone concentrations. The corticosterone response did not diminish with repeated GH challenge. These results suggest that GH may play a role in the acute regulation of corticosterone secretion in intact chickens.
Young cockerels (6-8 weeks old) were injected with serum from sheep immunized against somatostatin-14 (anti-SRIF) or normal sheep serum (NSS). Blood samples were withdrawn periodically for the determination of plasma corticosterone concentration by radioimmunoassay. With frequent (every 10 min) sampling, NSS-treated control animals exhibited increased plasma corticosterone levels, presumably as a stress response to the experimental manipulation. Anti-SRIF stimulated a much greater increase in plasma corticosterone concentrations and a peak response was observed within 10 to 20 min, when the plasma corticosterone level reached more than twice that of the corresponding control value. With less frequent sampling, plasma corticosterone increased with anti-SRIF administration to as much as nine times the corresponding control value, and the peak response occurred much later. Under pentobarbitone anaesthesia, which itself increased basal corticosterone concentrations, anti-SRIF treatment promoted further increases in plasma corticosterone levels although to a smaller magnitude compared with conscious birds. The results suggest that endogenous somatostatin may play a role in the regulation of adrenocortical function in the domestic fowl. The mechanism of response may involve a central component.
The rat liver microsomal vitamin K-dependent carboxylase catalyzes the carboxylation of glutamyl to gamma-carboxyglutamyl residues in the presence of reduced vitamin K, O2 and CO2. The specificity of the enzyme for the vitamin substrate has been probed by the synthesis of a number of menaquinone-2 (2-methyl-3-geranyl-1,4-naphthoquinone) derivatives. The 2-des-methyl and 2-ethyl-MK-2 derivatives had very low activity as substrates. The 6- or 7-methyl-MK-2 derivatives and (6,7)-chloro-MK-2 were relatively high Vmax substrates with Km values increased over that seen for K-2. The 5- or 8-methyl-MK-2 derivatives were low Vmax substrates but also demonstrated low Km values. Although these observations suggested that 5-methyl-MK-2 might be a competitive inhibitor of the carboxylation reaction, it was not an effective inhibitor of either phylloquinone or 6-methyl-MK-2-dependent carboxylation.
The biological activity of recombinant-DNA-derived chicken growth hormone (rcGH) has been examined in young broiler cockerels, by determining its effects on plasma concentrations of glucose, free fatty acids and alpha-amino nitrogen. A single injection of rcGH increased plasma glucose, which remained high for several hours, whereas daily treatment with rcGH for 1 week had no effect on basal plasma glucose concentrations but blunted the glucose response to a further rcGH challenge. Plasma free fatty acids were also promptly increased following acute rcGH treatment, and chronic exposure to rcGH again attenuated this response. The effects of rcGH on plasma alpha-amino nitrogen were more variable. The stress of repeated blood sampling tended to reduce alpha-amino nitrogen, and after rcGH, an increase relative to vehicle-injected controls was seen in both acute and chronically-treated birds. These data suggest that rcGH has both hyperglycaemic and lipolytic activity in chickens, and may also increase amino acid availability.
Isolated iliac artery aneurysms comprise less than 1% of all arteriosclerotic aneurysms. Spontaneous iliac arteriovenous fistula is a rare complication of these aneurysms with only 16 cases previously described. The diagnosis depends on a strong clinical suspicion and usually requires angiography for confirmation. We report a case in which CT with contrast medium showed clear findings of a spontaneous iliac arteriovenous fistula complicating rupture of an isolated iliac artery aneurysm. CT findings included: (1) iliac artery aneurysm, (2) vena caval dilatation, (3) rapid flow of contrast medium from the arterial side into the dilated inferior vena cava on dynamic scanning, (4) increased density of the inferior vena cava similar to that of the aorta caused by entry through the fistula of blood with a high concentration of iodinated contrast medium, and (5) the actual fistula connecting the two vessels.
The effects of serotoninergic drugs on adrenocortical function in domestic fowl were examined. Administration of the serotonin receptor agonist 2-(1-piperazinyl)quinoline maleate (quipazine), an inhibitor of serotonin metabolism, N-methyl-N-2-propynylbenzylamine HCl (pargyline), as well as serotonin itself, all increased plasma concentrations of corticosterone. The maximum responses to serotonin and quipazine occurred 1 h after treatment. The quipazine-stimulated response was partly prevented by the serotonin antagonist cyproheptadine. Cockerels pretreated with dexamethasone, a synthetic steroid known to inhibit pituitary ACTH release, showed attenuated responses to subsequent quipazine, pargyline or serotonin injection. Serotonin, quipazine and cyproheptadine did not affect corticosterone release directly from the adrenal gland incubated in vitro, nor did they affect adrenal responsiveness to ACTH stimulation. The neurotoxin 5,6-dihydroxytryptamine injected into day-old chicks decreased plasma concentrations of corticosterone for up to 7 days after treatment, with corresponding decreases in the hypothalamic concentration of serotonin, but not dopamine or noradrenaline concentrations. These results show that adrenal corticosterone secretion is regulated by a central serotoninergic system, probably acting on the hypothalamo-pituitary-adrenal axis.
The current status of pharmaceutical services in the Veterans Administration (VA) is described. The mission of the VA Department of Medicine and Surgery is to ensure that quality medical care is provided on a timely basis to all eligible veterans. The VA operates 172 medical centers and 225 ambulatory-care clinics, which makes the VA Pharmacy Service the largest multiinstitutional pharmacy system in the United States. VA pharmacy staffs in VA hospitals range in size from four or five people to more than 100 employees. The VA Pharmacy Service programs are divided into inpatient programs and ambulatory-care programs. Clinical pharmaceutical services and education and research activities are integrated into these programs. A Regional Pharmacy Advisory Council composed of chiefs of pharmacy service from seven geographical regions coordinates the exchange of information between the Central Office and the regions. Current issues of priority for the VA Pharmacy Service include human resource management, material resource management, information resource management, public relations, program enhancement, and new technology. The VA health-care system is comprehensive and complex, and the Pharmacy Service programs reflect the VA mission to provide quality services and support programs that will generate new information or knowledge to improve the care of veterans.
A proteinase inhibitor has been isolated from human colorectal adenocarcinomas by extraction with a low-ionic-strength buffer and a combination of Con A-Sepharose, Sephadex G-200, DEAE-cellulose and chromatofocusing steps. The preparation appeared to be homogeneous upon gel exclusion chromatography and SDS-polyacrylamide gel electrophoresis and had an estimated molecular weight of 66,000. The inhibitor was able to bind and inhibit urokinase, plasmin, trypsin, tissue plasminogen activator and thrombin. The binding appeared to be stoichiometric and relatively fast. The isoelectric point of the protein was 4.6-4.7. The inhibitor did not crossreact with antisera elicited against alpha 2-macroglobulin, alpha 2-antiplasmin, antithrombin III or C1-inhibitor, but it did crossreact with an antiserum against alpha 1-antitrypsin in double immunodiffusion. The antiserum only partially attenuated the activity of the inhibitor. Whereas alpha 1-antitrypsin completely inhibited the amidolytic activity of elastase, the tumor inhibitor had no effect on elastase under the same conditions.
We have isolated the bovine and human genes for Müllerian inhibiting substance (MIS), a testicular glycoprotein that causes regression of the Müllerian duct during development of the male embryo. The mRNA sequence of bovine MIS, determined from an analysis of cDNA and genomic clones, codes for a protein of 575 amino acids containing a 24 amino acid leader peptide. The human gene has five exons that code for a protein of 560 amino acids. A comparison of the bovine and human MIS proteins reveals a highly conserved C-terminal domain that shows marked homology with human transforming growth factor-beta and the beta chain of porcine inhibin. Animal cells transfected with the human gene secrete biologically active MIS, which causes regression of the rat Müllerian duct in vitro.
A plasminogen activator has been partially purified from benign serous cystadenomas by a combination of Sephadex G-200 gel filtration, CM-Sephadex ion exchange, Concanavalin A-Sepharose and arginine-Sepharose affinity chromatographies. Its apparent size was very large and could not penetrate Sepharose 6B or 5% SDS polyacrylamide gel. It hydrolyzed plasminogen in a manner similar to that of urokinase in terms of their apparent Michaelis constants, although a one-minute lag period had to be allowed for this activation before the hydrolysis of plasminogen. It was very sensitive to reducing agent such that 5 mM dithiothreitol could completely destroy its activity. The activator crossreacted with anti-uterine plasminogen activator IgG, but did not react with anti-urokinase at all. It also bound fibrin well. In the absence of plasminogen, the activator was devoid of amidolytic activity towards S-2251, S-2302 and S-2288 but had a small but measurable activity against S-2444.
Young leghorn cockerels were injected with antiserum to somatostatin (anti-SRIF) and plasma glucose, free fatty acids and alpha-amino nitrogen concentrations determined. Plasma glucose concentrations increased rapidly after anti-SRIF and remained high for up to 2 hr. Two different antisera tested had hyperglycaemic activity. Plasma free fatty acids also increased rapidly after administration of the two different anti-SRIFs, and remained high for about 1 hr. Plasma alpha-amino nitrogen increased during the first 30 min after anti-SRIF, then declined to levels significantly lower than control by 1-2 hr after injection. Anaesthesia reduced plasma concentrations of glucose and alpha-amino nitrogen, and also reduced the changes of these metabolites following anti-SRIF. The results show the importance of endogenous somatostatin in the regulation of plasma metabolite concentrations.