Biomedical subjects

M C Yang

Publications and source records attributed to M C Yang.

At least 55 records · Page 3Linked to original sources

PubMed1997

Inositol phosphate responses in portal veins from portal hypertensive rats: receptor- and nonreceptor-mediated responses.

BACKGROUND/AIMS: Venous hyporesponsiveness in portal hypertension has been reported previously by us. The present study was undertaken to investigate possible changes of phosphoinositide signal transduction pathway in the portal veins from portal hypertensive rats METHODS: Portal hypertension was induced by partial portal vein ligation. Fourteen days after surgery, portal veins were removed for measurement of [3H]inositol phosphate responses to both receptor- and nonreceptor-mediated stimuli. RESULTS: Basal [3H]inositol phosphate formation was similar between the two groups. Both phenylephrine and angiotensin II stimulated [3H]inositol phosphate formation in portal veins, but the responses were attenuated in the portal hypertensive group. In contrast, the [3H]inositol phosphate formation by nonreceptor-mediated stimuli (GTP gamma S, NaF/AlCl3, and phospholipase C) was similar between the two groups. CONCLUSION: Our results showed that the receptor-mediated [3H]inositol phosphate formation was attenuated, while the non-receptor-mediated formation was unaltered, in the portal vein from portal hypertensive rats.

Angiotensin II↗

PubMed1997

Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups.

Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.

Abatacept↗

PubMed1997

Evaluating the merits of option-3 methods in relative attachment level measurement in a healthy population.

Attachment loss is the principal clinical indicator for periodontal disease progression. However, the attachment measurement can be inaccurate due to outliers. A remedial scheme, the option-3 scheme, has been suggested in the literature. This scheme involves first measuring the relative attachment twice at any given site. A third measurement is required if there is a large disagreement between the first two probings. When the third measurement is taken, there are several possible ways to make the final assessment of the true attachment level. Among them are the average of the 3 measurements, the average of the closest 2, and the median of the 3. This report evaluates the merits of the option-3 scheme by comparing it with other schemes to reduce measurements variance and outliers. Since true attachment levels are unknown, we chose to check accuracy through measurement consistency between visits in healthy subjects using the fact that such subjects should have little real change in attachment levels. 12 healthy subjects participated in the study. They visited the clinic 4 times in 4 months. Two types of the Florida stent probe were used by 2 calibrated examiners. It was found that option-3 schemes were more accurate than a single probing or duplicate probings in estimating the relative attachment level. The 3 final assessment schemes performed almost equally well from a practical standpoint, but the median was the best among them in a statistical sense.

Adult↗

PubMed1997

Recombinant Coccidioides immitis complement-fixing antigen: detection of an epitope shared by C. immitis, Histoplasma capsulatum, and Blastomyces dermatitidis.

We undertook an investigation to assess the utility of a recombinant Coccidioides immitis complement-fixing (CF) antigen for detecting CF antibody in sera from patients with coccidioidomycosis. Enzyme-linked immunosorbent assays established that recombinant CF antigen and, for comparison, a commercially available coccidioidin were reactive with 19 of 19 sera from patients with active coccidioidomycosis. The recombinant antigen was significantly more sensitive than coccidioidin. The median titer obtained when patients' sera were assayed against recombinant CF antigen was 1:51,200 compared to 1:25,600 with coccidioidin (P < 0.027). The recombinant antigen was also more effective in distinguishing the antibody levels in sera from patients with pulmonary coccidioidomycosis than in sera from those with disseminated disease. Whereas patients with pulmonary disease showed a median antibody titer of 1:25,600, those with multifocal disease showed a median titer of 1:102,400 (P < 0.028). The recombinant CF antigen was found, however, to express an epitope(s) that reacted with sera from 6 of 12 patients with histoplasmosis and 2 of 12 patients with blastomycosis.

Antibodies, Fungal↗

PubMed1997

Mapping of a Coccidioides immitis-specific epitope that reacts with complement-fixing antibody.

We have previously cloned the cDNA fragment that encodes the complement fixation antigen of Coccidioides immitis. The recombinant protein was highly sensitive in detecting CF antibody in sera from patients with coccidioidomycosis but was not specific to C. immitis, as evidenced by its reactivity with sera from patients with histoplasmosis and, to lesser extent, blastomycosis. We undertook this study to determine if the epitope(s) that reacts with CF antibody is the same or differs from the epitopes that are shared with Histoplasma capsulatum and Blastomyces dermatitidis. PCR-generated CF/chitinase cDNA fragments were cloned and examined for their reactivity in enzyme-linked immunosorbent assays using sera from patients with coccidioidomycosis, histoplasmosis, or blastomycosis. A peptide domain comprised of amino acid residues 20 through 310 was shown to express an epitope(s) that is specific to anti-Coccidioides CF antibody. The peptide detected serum antibody in 21 (95%) of 22 patients with active coccidioidomycosis and was without reactivity with sera from 20 patients with histoplasmosis, 15 patients with blastomycosis, and 14 healthy subjects. Antibody titers to the recombinant peptide directly correlated with CF antibody titers (P < 0.01), and preadsorption of reference CF antiserum with the peptide ablated the reactivity of the antiserum in the immunodiffusion assay for CF antibody. The delineation of a recombinant peptide that has both sensitivity and specificity will provide a valuable tool for detecting CF antibody and for evaluating the role of CF antibody in the host response to C. immitis.

Antibodies, Fungal↗

PubMed1997

The hemodynamic effects of AT-112, an analog of ketanserin, in portal hypertensive rats.

A serotonin mechanism has been reported to contribute to the hyperdynamic circulation of portal hypertension. Different studies have demonstrated that serotonin antagonists decrease portal pressure in portal hypertensive patients and animals. The present study was undertaken to investigate the effect of AT-112, an analog of ketanserin, on portal hypertension induced by partial portal vein ligation in rats. Since ketanserin is known to possess alpha 1-adrenergic antagonistic activity, the effect of AT-112 was compared to that of prazosin. A single dose (prazosin 4.2 micrograms/kg, AT-112 1 mg/kg) was chosen to produce a similar hypotensive effect (-20 +/- 4% for prazosin and -24 +/- 4% for AT-112). At this dose, prazosin significantly decreased total peripheral resistance whereas AT-112 significantly decreased cardiac index and heart rate. Both agents significantly decreased the portal tributary blood flow and portal pressure. In rats receiving AT-112, a significant correlation was found between the magnitudes of decrease in cardiac index and the decrease in portal tributary blood flow. We also found that the magnitude of reduction in portal pressure was greater following AT-112 administration. This study suggested that AT-112 may have more beneficial hemodynamic effects than prazosin in portal hypertensive rats. Our results provide further support for the serotonergic mechanism in the pathogenesis of hyperdynamic circulation in portal hypertension.

Animals↗

PubMed1997

Hemodynamic effects of chronic tetrandrine and propranolol administration on portal hypertensive rats.

The purpose of this study was to investigate the therapeutic effects of tetrandrine and propranolol, alone or in combination, on portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Animals were allocated into one of the four groups: vehicle group (0.1 N.HCl, 0.7 ml/day), tetrandrine group (50 mg/kg/ day), propranolol group (30 mg/kg/day), and tetrandrine (50 mg/kg/day) plus propranolol (30 mg/kg/day) group. Drug or vehicle was administered by gavage for consecutive 9 days. After 9 days of treatment, the portal venous pressure and mean arterial pressure in each treatment group were significantly lower than those in the vehicle group. The cardiac index was not changed by tetrandrine alone, but reduced in the two groups receiving propranolol alone or in combination. Total peripheral resistance was significantly decreased in the tetrandrine group and significantly increased in the tetrandrine plus propranolol group as compared with the vehicle group. Our results suggested that tetrandrine or propranolol alone induced portal hypotensive effects, with propranolol achieving better antihyperdynamic effects in terms of cardiac index, and in combination propranolol effects predominated over those of tetrandrine.

Administration, Oral↗

PubMed1996

The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase.

The TIS21 immediate-early gene and leukemia-associated BTG1 gene encode proteins with similar sequences. Two-hybrid analysis identified a protein that interacts with TIS21 and BTG1. Sequence motifs associated with S-adenosyl-L-methionine binding suggested this protein might have methyltransferase activity. A glutathione S-transferase (GST) fusion of the putative methyltransferase modifies arginine residues, in appropriate protein substrates, to form NG-monomethyl and NG,NG-dimethylarginine (asymmetric). We term the protein- arginine N-methyltransferase (EC 2.1.1.23) gene "PRMT1, " for protein-arginine methyltransferase 1. GST-TIS21 and GST-BTG1 fusion proteins qualitatively and quantitatively modulate endogenous PRMT1 activity, using control and hypomethylated RAT1 cell extracts as methyl-accepting substrates. PRMT1 message appears ubiquitous, and is constitutive in mitogen-stimulated cells. Modulation of PRMT1 activity by transiently expressed regulatory subunits may be an additional mode of signal transduction following ligand stimulation.

Amino Acid Sequence↗

PubMed1996

The predominant protein-arginine methyltransferase from Saccharomyces cerevisiae.

We have identified the major enzymatic activity responsible for the S-adenosyl-L-methionine-dependent methylation of arginine residues (EC 2.1.1.23) in proteins of the yeast Saccharomyces cerevisiae. The RMT1 (protein-arginine methyltransferase), formerly ODP1, gene product encodes a 348-residue polypeptide of 39.8 kDa that catalyzes both the NG-mono- and NG, NG-asymmetric dimethylation of arginine residues in a variety of endogenous yeast polypeptides. A yeast strain in which the chromosomal RMT1 gene was disrupted is viable, but the level of NG,NG-[3H]dimethylarginine residues detected in intact cells incubated with S-adenosyl-L-[methyl-3H]methionine is reduced to less than 15% of the levels found in the parent strain, while the NG-[3H]monomethylarginine content is reduced to less than 30%. We show that soluble extract from parent cell, but not from mutant rmt1 cells, catalyzes the in vitro methylation of endogenous polypeptides of 55, 41, 38, 34, and 30 kDa. The hypomethylated form of these five polypeptides, as well as that of several others, can be mono- and asymmetrically dimethylated by incubating the mutant rmt1 extract with a purified, bacterially produced, glutathione S-transferase-RMT1 fusion protein and S-adenosyl-L-[methyl-3H]methionine. This glutathione S-transferase-RMT1 fusion protein is also able to methylate a number of mammalian polypeptides including histones, recombinant heterogeneous ribonucleoprotein A1, cytochrome c, and myoglobin, but cannot methylate myelin basic protein. RMT1 appears to be a yeast homolog of a recently characterized mammalian protein-arginine methyltransferase whose activity may be modulated by mitotic stimulation of cells.

Amino Acid Sequence↗

PubMed1996

Effects of long-term administration of octreotide in portal vein-stenosed rats.

The hemodynamic effects of long-term administration of octreotide in portal hypertension has not been established. In addition, whether long-term octreotide treatment prevents the development of portosystemic shunts has not yet been evaluated. Hence, the current study was undertaken to evaluate the effects of long-term administration of octreotide in rats with portal vein stenosis. Immediately after portal vein stenosis or sham operation, rats were given either a long-term octreotide administration of 100 micrograms/kg or a placebo every 12 hours by subcutaneous injection for 14 consecutive days. Systemic hemodynamics and regional blood flows, degree of mesenteric-systemic shunts, and plasma glucagon concentrations were measured after the final dose of octreotide or placebo. A fifth group of portal vein-stenosed rats received hemodynamic and plasma glucagon measurements after 1-day octreotide treatment given at 14 days after surgery. Long-term octreotide treatment modified the hyperdynamic circulation without affecting the degree of mesenteric-systemic shunts, and 1-day octreotide treatment decreased portal tributary blood flow without affecting the portal pressure, systemic hemodynamics, and degree of mesenteric-systemic shunts. Plasma glucagon levels were decreased in portal vein-stenosed rats receiving either long-term or 1-day octreodtide compared with rats receiving placebo. In contrast, chronic octreotide treatment did not affect any of the hemodynamic values or plasma glucagon levels in sham-operated rats. In conclusion, long-term administration of octreotide modified in part the development of portal hypertension and hyperdynamic circulation in portal vein-stenosed rats without affecting the degree of mesenteric-systemic shunts.

Analysis of Variance↗

PubMed1996

Surgical treatment of hepatocellular carcinoma originating from the caudate lobe.

Hepatocellular carcinoma (HCC) originating from the caudate lobe is rare, and its surgical management is difficult because of its unique anatomic location. We have seen six such cases at our hospital. For patients with fair to excellent liver reserve, we advocated caudate lobectomy combining other types of hepatic resection. For patients with marked liver cirrhosis and poor liver reserve or a small HCC, we advocated simple partial caudate lobectomy (limited hepatic resection). There was no operative mortality or major operative morbidity. We conclude that such approaches are safer, less time-consuming, and less technique-demanding, and they produce a fair survival result compared with the approaches of other procedures. With such approaches, it is our experience that patients with HCC from the caudate lobe have a prognosis comparable to that of patients with HCC in other parts of the liver.

Adult↗

PubMed1996

Decreased vascular reactivity of portal vein in rats with portal hypertension.

BACKGROUND/AIMS: Vascular hyporesponsiveness in portal hypertension is well documented in the arterial tissue. The present study aimed to investigate the possible changes in the portal vein from portal hypertensive rats. METHODS: Portal hypertension was induced by partial portal vein ligation. Fourteen days after surgery, portal veins were removed for contractile study and measurement of cAMP, cGMP and [Ca2+]i. RESULTS: In vitro tension preparation showed a decreased maximum response to norepinephrine in portal vein of portal vein ligated rats (38.3 +/- 4.1 vs. 23.4 +/- 1.5 mN/mm2). The pA2 values of WB4101 and yohimbine (alpha1- and alpha2-adrenoceptor antagonist, respectively) were not different between the two groups. Tissue cAMP (14.4 +/- 0.9 vs. 12.2 +/- 0.7 pmol/mg protein), but not cGMP, content was increased and intracellular calcium [Ca2+]i levels (247 +/- 9 vs. 281 +/- 13 nM) were decreased in portal vein ligated rats. CONCLUSIONS: These results showed that in portal vein from portal vein ligated rats, vascular hyporesponsiveness and an increase in basal cAMP content and a decrease in basal [Ca2+]i were observed.

Animals↗

PubMed1996

Effect of octreotide on total effective vascular compliance in patients with posthepatitic cirrhosis.

BACKGROUND/AIMS: This study aimed to evaluate the effect of octreotide on total effective vascular compliance, measured during rapid volume expansion, in patients with posthepatitic cirrhosis. METHODS: Twenty-nine patients with posthepatitic cirrhosis were randomly assigned to receive a 100-micrograms/h infusion of octreotide after a 100-micrograms bolus (n = 15), or a placebo (n = 14). Hemodynamic measurements were recorded before and 30 min after drug administration. Thereafter, rapid volume expansion was performed in each patient and hemodynamic measurements were repeated immediately after volume expansion. RESULTS: Before volume expansion, placebo administration did not affect any of the hemodynamic values, while the hepatic blood flow was significantly decreased following octreotide administration. After volume expansion, the hemodynamic changes were similar between patients receiving octreotide and the placebo. However, the increase in right atrial pressure from the beginning to the end of volume expansion was higher and the total effective vascular compliance was lower in patients receiving octreotide (+3.5 +/- 0.3 mmHg, p = 0.05 and 1.69 +/- 0.16 ml.mmHg-1.kg-1, p < 0.05) compared to patients receiving placebo (+2.5 +/- 0.3 mmHg, 2.60 +/- 0.34 ml.mmHg-1.kg-1). CONCLUSIONS: The present study suggests that octreotide decreased total effective vascular compliance in patients with posthepatitic cirrhosis. It is possible that, in patients with posthepatitic cirrhosis, venoconstriction was induced following octreotide administration.

Aged↗

PubMed1996

Identification of a RING protein that can interact in vivo with the BRCA1 gene product.

The hereditary breast and ovarian cancer gene, BRCA1, encodes a large polypeptide that contains the cysteine-rich RING motif, a zinc-binding domain found in a variety of regulatory proteins. Here we describe a novel protein that interacts in vivo with the N-terminal region of BRCA1. This BRCA1-associated RING domain (BARD1) protein contains an N-terminal RING motif, three tandem ankyrin repeats, and a C-terminal sequence with significant homology to the phylogenetically conserved BRCT domains that lie near the C terminus of BRCA1. The BARD1/BRCA1 interaction is disrupted by BRCA1 missense mutations that segregate with breast cancer susceptibility, indicating that BARD1 may be involved in mediating tumour suppression by BRCA1.

Amino Acid Sequence↗

PubMed1996

Chronic administration of octreotide increases vascular responsiveness in rats with portal hypertension.

1. It has been reported that ortreotide partially corrects the hyperdynamic state in patients and animals with portal hypertension. The aim of the present study was to investigate whether chronic administration of octreotide can increase vascular responsiveness in rats with portal hypertension. 2. Portal hypertension was induced by partial portal vein ligation. Octreotide was given for 9 days subcutaneously (100 micrograms/kg every 12 h) starting 1 day before ligation. The aorta and mesenteric artery were then removed to study contraction after pressure recording. 3. Octreotide treatment significantly reduced portal pressure and plasma glucagon concentrations compared with the vehicle-treated group. Both phenylephrine and vasopressin induced concentration-dependent contractile responses in the aorta and mesenteric artery from both groups. The maximum contractile responses to phenylephrine and vasopressin in aorta and mesenteric artery were significantly greater in the octreotide-treated group than in the vehicle-treated group. The EC50 values for phenylephrine and vasopressin were significantly different in the aorta, but not in the mesenteric artery, but not in the mesenteric artery, between the two groups. In contrast, octreotide treatment did not alter the contractile responsiveness of arteries rom sham-operated rats. 4. These results show that, in rats with portal vein stenosis, octreotide increases arterial contractile responsiveness and reduces portal pressure.

Animals↗

PubMed1996

Role of endotoxaemia in hyperdynamic circulation in rats with extrahepatic or intrahepatic portal hypertension.

This study investigated the role of endotoxaemia in the development of hyperdynamic circulation observed in rats with extrahepatic (high collateralization) or intrahepatic (low collateralization) portal hypertension. Compared with sham-operated rats, decreased mean arterial pressure and systemic vascular resistance were detected on days 1, 4, and 14 following partial portal vein ligation. By day 1, the cardiac index of portal vein-ligated rats was similar to that of sham-operated rats and progressively increased, thereafter, reaching statistically higher values days 4 and 14. No differences in plasma endotoxin levels were found between portal vein-ligated and sham-operated rats throughout the observation period. Both carbon tetrachloride-induced cirrhotic rats with and without ascites had a higher cardiac index and lower systemic vascular resistance. Plasma endotoxin levels were higher in cirrhotic rats with ascites (8.6 +/- 2.0 pg/mL; P < 0.01) than those of control rats (2.2 +/- 0.3 pg/mL) and cirrhotic rats without ascites (2.4 +/- 0.6 pg/mL). These results suggest that factors other than endotoxaemia play a role in the development of hyperdynamic circulation observed in rats with extrahepatic portal hypertension and cirrhotic rats without ascites, but that endotoxaemia may contribute to the maintenance of hyperdynamic circulation found in cirrhotic rats with ascites. The severity of liver disease may be a more important factor than the presence of portosystemic shunting for the development of endotoxaemia in portal hypertensive states.

Animals↗

PubMed1996

Hyperglucagonaemia in cirrhotic patients and its relationship to the severity of cirrhosis and haemodynamic values.

Plasma glucagon concentrations were measured in 160 cirrhotic patients (Pugh's grade A in 52 patients, Pugh's grade B in 64 patients and Pugh's grade C in 44 patients). These values were compared with plasma glucagon concentrations in 57 age and sex-matched healthy subjects. Systemic and portal haemodynamic measurements, effective renal plasma flow and creatinine clearance were recorded for each patient. Plasma glucagon levels were significantly increased in cirrhotic patients compared with healthy subjects. In addition, plasma glucagon levels were higher in cirrhotic patients with ascites than in those without ascites and were increased in relation to the severity of cirrhosis as assessed by Pugh's score. Multiple linear regression found that only Child-Pugh's score was estimated to be an independent predictor of hyperglucagonaemia in cirrhotic patients. However, in patients with different degrees of oesophageal varices and in patients without oesophageal varices, plasma glucagon concentrations were no different among the different groups of patients, but were still higher than plasma glucagon concentrations in healthy subjects. In contrast, plasma glucagon levels were negatively correlated with mean arterial pressure and systemic vascular resistance. The results of the present study suggest that impairment of liver function plays, in part, a role in increased plasma glucagon levels observed in patients with cirrhosis. In addition, these data support the hypothesis that hyperglucagonaemia may contribute, at least in part, to the pathogenesis of peripheral arterial vasodilatation in cirrhosis with portal hypertension.

Adult↗

PubMed1996

Effect of verapamil on renal haemodynamics in a portal hypertensive rat model.

In order to investigate the effects of verapamil on renal haemodynamics in rats with portal hypertension, verapamil was given at either a low (0.2 mg/kg) or high (2 mg/kg) dose to rats after portal vein ligation. An approximate 12% decrease in mean arterial pressure followed administration of low dose verapamil, with a significant decrease in cardiac output and renal blood flow, as well as reduced portal pressure, observed; these signs were all indicative of a rise in renal vascular resistance. In contrast, the marked fall in both mean arterial pressure and cardiac output with high dose verapamil, accompanied by a significant decrease in portal pressure and no change in renal blood flow, suggests a reduction in renal vascular resistance. This study shows that the acute effects of verapamil on renal haemodynamics may vary with the dose used. Also, acute verapamil administration tends to decrease renal blood flow to alter the autoregulation of the kidney; thus, caution should be taken in the clinical use of verapamil in the treatment of cirrhosis with portal hypertension.

Animals↗