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Biomedical subjects

S M Huang

Publications and source records attributed to S M Huang.

At least 73 records · Page 4Linked to original sources
PubMed1998

Troglitazone monotherapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled study. The Troglitazone Study Group.

To assess the effects of troglitazone monotherapy on glycemic control in patients with type 2 diabetes mellitus, we carried out a 6-month, randomized, double-blind, placebo-controlled study in 24 hospital and outpatient clinics in the United States and Canada. Troglitazone 100, 200, 400, or 600 mg or placebo once daily with breakfast was administered to 402 patients with type 2 diabetes with fasting serum glucose (FSG) > 140 mg/dL, glycosylated hemoglobin (HbA1c) > 6.5%, and fasting C-peptide > or = 1.5 ng/mL. Prior oral hypoglycemic therapy was withdrawn in patients who received it before the study. FSG, HbA1c, C-peptide, and serum insulin were evaluated at baseline and the end of the study. Analysis was performed on two subsets of patients based on prestudy therapy: Patients treated with diet and exercise only before the study (22% of patients), and those who had been receiving sulfonylurea therapy (78% of patients). Patients treated with 400 and 600 mg troglitazone had significant decreases from baseline in mean FSG and HbA1c at month 6 compared with placebo-treated patients (FSG: -51 and -60 mg/dL, respectively; HbA1c: -0.7 and -1.1%, respectively). In the diet-only subset, 600 mg troglitazone therapy resulted in a significant (P < 0.05) reduction in HbA1c (-1.35%) and a significant reduction in FSG (-42 mg/dL) compared with placebo. Patients previously treated with sulfonylurea therapy had significant (P < 0.05) decreases in mean FSG with 200-600 mg troglitazone therapy compared with placebo (-48, -61, and -66 mg/dL, respectively). Significant (P < 0.05) decreases in mean HbA1c occurred with 400 and 600 mg troglitazone therapy at month 6 (-0.8 and -1.2%, respectively) compared with placebo in this same subset. Significant (P < 0.05) decreases in triglycerides and free fatty acids occurred with troglitazone 400 and 600 mg, and increased high-density lipoprotein occurred with 600 mg troglitazone. We conclude that troglitazone monotherapy significantly improves HbA1c and fasting serum glucose, while lowering insulin and C-peptide in patients with type 2 diabetes. Troglitazone 600 mg monotherapy is efficacious for patients who are newly diagnosed and have never received pharmacological intervention for diabetes.

Aged↗
PubMed1998

Estrogen receptor activation function 1 works by binding p160 coactivator proteins.

Estrogen receptor-alpha contains two transactivation functions, a weak constitutive activation function (AF-1) and a hormone-dependent activation function (AF-2). AF-2 works by recruiting a large coactivator complex, composed of one or more p160s, CREB-binding protein (CBP)/p300, and P/CAF (p300 and CBP-associated factor), via direct contacts with the p160s. We report here that independent AF-1 activity also requires p160 contacts. Unlike AF-2, which binds signature NR boxes in the center of the p160 molecule, AF-1 binds to sequences near the p160 C terminus. We propose that the ability of AF-1 and AF-2 to interact with separate surfaces of the same coactivator is important for the ability of these transactivation functions to synergize.

Acetyltransferases↗
PubMed1998

Donor leukocyte infusion as salvage therapy in an adult with relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation.

Relapse of malignancy after allogeneic bone marrow transplantation remains the major cause of treatment failure in patients with leukemia. While donor leukocyte infusion (DLI) has been used to treat such patients, its use in patients with acute lymphoblastic leukemia is seldom reported. We describe a 35-year-old woman who suffered relapse of acute lymphoblastic leukemia after allogeneic bone marrow transplantation. She received DLI twice as salvage therapy. This patient achieved complete remission following DLI and has remained in remission for more than 11 months without further chemotherapy. We suggest DLI can be used as an initial salvage therapy, without significant toxicity, for patients with relapsed acute lymphoblastic leukemia following bone marrow transplantation.

Adult↗
PubMed1998

A modified design of microwave tissue coagulator monopolar antenna for applications in laparoscopic hepatic surgery.

Massive hemorrhage is of primary concern during hepatic surgery. In this study, we not only modified the monopolar antenna of the microwave tissue coagulator but also investigated its feasible applications in laparoscopic hepatic surgery. In addition, the conventional antenna of the microwave tissue coagulator was used as a model. A catheter was attached to the antenna. The network analyzer was used to analyze the impedance of the novel monopolar antenna. Moreover, we designed and constructed a novel monopolar antenna for the microwave tissue coagulator. The antenna is gas-leak-proof, having sufficient stiffness and length and retaining similar microwave emission strength, pattern, and shielding property as the conventional antenna. In vitro tests in porcine liver confirm the coagulation and hemostatic effects of the novel type laparoscopic monopolar antenna. Results presented herein confirm the effectiveness of a laparoscopic monopolar antenna for a microwave tissue coagulator with sufficient coagulation effects.

Animals↗
PubMed1998

ATRA-induced pseudotumour cerebri--one case report.

A 17-year-old girl with acute pomyelocytic leukemia (APL) went into complete remission following Daunorubicin, Ara-C and ATRA chemotherapy for 1 month. Unfortunately, prolonged administration of ATRA 6 weeks later caused binocular diplopia with left abducent nerve paresis, which gradually disappeared upon withdrawal of ATRA. We propose that it is ATRA induced pseudotumour cerebri and present this case to discuss the relationship between the ATRA and pseudotumour cerebri.

Adolescent↗
PubMed1997

Consequences of metabolic inhibition in smooth muscle isolated from guinea-pig stomach.

1. In smooth muscle isolated from the guinea-pig stomach, cyanide (CN) and iodoacetic acid (IAA) were applied to block oxidative phosphorylation and glycolysis, respectively. Effects of IAA on generation of spontaneous mechanical and electrical activities were systematically investigated by comparing those of CN. Spontaneous activity ceased in 10-20 min during applications of 1 mM IAA. On the other hand, application of 1 mM CN also reduced the spontaneous activity, but never terminated it. In the presence of CN the negativity of the resting membrane potential was slightly reduced. 2. When spontaneous activity ceased with IAA, the resting membrane potential was not significantly affected. Also, before ceasing, the amplitude and duration of the spontaneous electrical activity were significantly reduced. The amplitude of the electrotonic potential was, however, not changed by IAA. Further, glibenclamide did not prevent the effects of IAA. These results suggest that, unlike cardiac muscle, activation of metabolism-dependent K+ channels in stomach smooth muscle does not seem to play a major role in reducing and terminating spontaneous activity during metabolic inhibition. 3. Carbachol-induced contraction transiently increased, and subsequently decreased gradually during application of IAA. 4. After 50 min application of IAA, when there was no spontaneous activity, the concentrations of phosphocreatine (PCr) and ATP measured with 31P nuclear magnetic resonance decreased to 60 and 80% of the control, respectively, while inorganic phosphate (Pi) concentration paradoxically fell to below detectable levels. During subsequent prolonged application of IAA, high-energy phosphates steadily decreased. On the other hand, after 50 min CN application, [PCr] and [ATP] decreased to approximately 30 and 80% of the control, respectively, while [Pi] increased by 2.6-fold. 5. In the presence of either CN or IAA, spontaneous mechanical and electrical activities were reduced or eliminated, although amounts of high-energy phosphates sufficient to contract smooth muscle remained. It can be postulated that some mechanism(s) related to energy metabolism, but not including ATP-sensitive K+ channels, plays an important role in generating spontaneous activity in guinea-pig stomach smooth muscle. During metabolic inhibition the energy metabolism-dependent mechanism(s) would preserve high-energy phosphates, and consequently cell viability, by stopping spontaneous activity.

Adenosine Triphosphate↗
PubMed1997

Familial hyperparathyroidism without multiple endocrine neoplasia.

Hyperparathyroidism occurs sporadically, in association with multiple endocrine neoplasia (MEN) types I and II, or rarely as familial hyperparathyroidism (FHPT) without other manifestations. We analyzed our experience in 16 FHPT patients from 14 families treated between 1934 and 1991 and reviewed 51 other FHPT patients reported in the literature to determine the clinical course of these patients. Among our 16 patients, 7 (44%) had a serum calcium level >/= 3.75 mmol/L, 5 (31%) presented with hypercalcemic crisis, 3 (19%) had osteitis fibrosa cystica, 5 (31%) had nephrolithiasis, 1 had pancreatitis, 12 (75%) had multiple abnormal parathyroid glands, 3 (19%) had supernumerary glands, and 7 (44%) required reoperation for persistent (n = 4) or recurrent (n = 3) hyperparathyroidism. Three patients (19%) also had papillary thyroid cancer, and 7 (44%) had other coexistent thyroid disorders. Among 51 patients with FHPT reported in the literature, 23 (45%) had serum calcium >/= 3.75 mmol/L, and 23 (45%) had multiple abnormal parathyroid glands; 10 (20%) had recurrent hyperparathyroidism. FHPT without other endocrinopathies is a distinct entity. Patients with FHPT have multiple abnormal parathyroid glands and are prone to both recurrent and persistent hyperparathyroidism. They frequently present with profound hypercalcemia or hypercalcemic crisis, in contrast to patients with MEN-associated hyperparathyroidism or sporadic hyperparathyroidism.

Adolescent↗
PubMed1997

Expression of vascular endothelial growth factor in normal liver and hepatocellular carcinoma: an immunohistochemical study.

Angiogenesis is of vital importance during the development and progression of solid tumors. To examine the role of vascular endothelial growth factor (VEGF) in hepatocarcinogenesis, we evaluated the expression of peptide in normal human liver (n = 6) and in 36 cases of hepatocellular carcinoma (HCC). Immunoreactivity for VEGF was present in the extracellular matrix of the portal tracts in the normal and nontumor part of liver, but not in hepatocytes and bile duct epithelium. For HCC, variable amounts of VEGF were expressed in 13 cases (36.1%) of tumor cells. Using a logistic regression model, expression of VEGF was significantly associated with a higher proliferative index (P = .01) and sonographic portal vein thrombosis (P = .05). However, VEGF expression did not correlate with a biochemical liver profile, alpha-fetoprotein levels, histological grading, gender, or clinical stage of cirrhosis (P > 0.1, respectively). Log-rank test showed that evaluation of VEGF did not provide more prognostic information (P > .5) than that from tumor volume and portal vein thrombosis (P < .01, respectively). In addition, VEGF was always present in the fibrovascular stroma or pericellular matrix of HCC, although no strong relationship was observed with the expression of VEGF in tumor cells (P > .5). Our data suggested that expression of VEGF may characterize a progression toward higher proliferation in hepatocarcinogenesis in vivo. The relevance of VEGF existing in the extracellular matrix of the normal liver and HCC remains to be clarified.

Adolescent↗
PubMed1997

Functional roles of the N-terminal amino acid residues in the Mn(II)-L-malate binding and subunit interactions of pigeon liver malic enzyme.

Pigeon liver malic enzyme has an N-terminal amino acid sequence of Met-Lys-Lys-Gly-Tyr-Glu-. In this work, various mutants of the enzyme with individual or combinational deletion (delta) or substitution at these amino acids were constructed and functionally expressed in Escherichia coli cells. A major protein band corresponding to an Mr of approximately 65000 was observed for all recombinant enzymes in sodium dodecyl sulfate polyacrylamide gel electrophoresis. However, when examining by polyacrylamide gel electrophoresis under native conditions, the recombinant enzymes were found to possess a tetrameric structure with Mr approximately 260000 or a mixture of tetramers and dimers with the exception of delta(K2K3G4) and delta(1-16) mutants, which existed exclusively as dimers at the protein concentration we employed. K3A and K3E also dissociated substantially. K(2,3)A was a tetramer but K(2,3)E essentially existed as dimers. All tetramers and dimers were enzymatically active in the gels. All mutants displayed a similar apparent Km value for NADP+. The apparent Km for L-malate and Mn(II), on the other hand, was increased by 4-27-fold for the delta(K2/K3) and the delta(1-16) mutants. The small binding affinity of delta(K2/K3) with Mn(II)-L-malate was specific. With additional deletion at positions 3 and/or 4, the delta(K2K3), delta(K2G4/K3G4) or delta(K2K3G4) mutants exhibited similar kinetic properties for the wild type. The lysine residues at the positions 2 or 3 seem to be crucial for the correct active site conformation. The results indicate that the N-terminus of malic enzyme is located at the Mn(II)-L-malate binding domain of the active center and is also near the subunit's interface. These results were interpreted with our asymmetric double-dimer model for the enzyme in which the N-terminus was involved in the head-to-tail monomer-monomer interactions but not the dimer-dimer interactions.

Animals↗
PubMed1997

Effect of thyroid hormone on urinary excretion of epidermal growth factor.

Thyroid hormones were demonstrated to upregulate the synthesis of epidermal growth factor (EGF) mRNA and proEGF in the kidneys in vivo. This prospective study was performed to examine the extent of the hypothyroid state in modulating EGF excretion in the urine (U-EGF; n = 23). Patients with thyroid cancer were serially followed up from the euthyroid status, which was retained by thyroxine supplement after thyroidectomy, to the hypothyroidism in preparing for 131I whole body scanning. Paired thyroid function panel, including triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and U-EGF levels were measured on a weekly basis. Logarithmically transformed values of U-EGF were inversely correlated with TSH serum levels (p = 0.0000), but positively associated with T4 levels (p = 0.0005). No apparent correlation was observed with the T3 serum content, age and gender of the patients (p > 0.1, respectively). If the interval of measurement was taken into consideration, serum TSH was the most significant factor in association with U-EGF (p = 0.0003). Our data indicate that excretion of EGF in human urine depends substantially upon thyroid hormone support.

Adult↗
PubMed1997

Cardiac and glycemic benefits of troglitazone treatment in NIDDM. The Troglitazone Study Group.

Troglitazone is a thiazolidinedione under development for the treatment of NIDDM and potentially other insulin-resistant disease states. Treatment with troglitazone is associated with an improvement in hyperglycemia, hyperinsulinemia, and insulin-mediated glucose disposal. No significant side effects have been observed in humans. Because of reported cardiac changes in animals treated with drugs of this class, this multicenter 48-week study was conducted to evaluate whether NIDDM patients treated with troglitazone develop any cardiac mass increase or functional impairment. A total of 154 NIDDM patients were randomized to receive troglitazone 800 mg q.d. or glyburide titrated to achieve glycemic control (< or =20 mg b.i.d. or q.d.). Two-dimensional echocardiography and pulsed Doppler were used to measure left ventricular mass index (LVMI), cardiac index (CI), and stroke volume index (SVI). All echocardiograms were performed at each center (baseline, 12, 24, 36, and 48 weeks), recorded on videotape, and forwarded to a blinded central echocardiographic interpreter for analysis. The results showed that LVMI of patients treated with troglitazone was not statistically or clinically different from baseline after 24 or 48 weeks. Statistically significant increases in SVI and CI and a statistically significant decrease in diastolic pressure and estimated peripheral resistance were observed in troglitazone-treated patients. These results were not sex-specific. Glycemic benefits of troglitazone treatment were observed as evidenced by long-term improvement of HbA1c and C-peptide levels. Furthermore, triglycerides were significantly lower, and HDL was significantly higher at weeks 24 and 48. In conclusion, NIDDM patients treated with troglitazone do not show any cardiac mass increase or cardiac function impairment. Conversely, patients on troglitazone benefited from enhanced cardiac output and stroke volume, possibly as a result of decreased peripheral resistance. Treatment with troglitazone appears to have a favorable impact on known cardiovascular risk factors and could potentially lower cardiovascular morbidity in NIDDM patients.

Blood Glucose↗
PubMed1997

[Clinical report of 60 cases of diabetic cardio-vascular autonomous neuropathy by stasis removing treatment of combined traditional and Western medicine].

OBJECTIVE: To study the treatment of diabetic cardio-vascular autonomous neuropathy (DCVAN) by TCM-WM following the principle of promoting blood circulation to remove blood stasis. METHODS: Sixty patients with DCVAN were randomly divided into two groups, the treatment group (30 patients) were treated with combined TCM-WM therapy. Based on the control of blood sugar by WM effectively, then use TCM-Tangxinshen ([symbol: see text], TXS) with the function of supplementing the Qi and nourishing Yin, promoting blood circulation to remove blood stasis. Thirty cases of the control group were treated with WM alone. The course of treatment was three months. RESULTS: The total effective rate of the treatment group and the control group was 77.3% and 33.4% respectively, which were significantly different statistically (P < 0.005). CONCLUSION: The therapeutic effect of TCM-WM was better than that of WM.

Adult↗
PubMed1997

Comparison of intravenous granisetron with metoclopramide plus dexamethasone in the prevention of nausea and vomiting associated with emetogenic cytotoxic chemotherapy.

Fifty-one patients who received their first course of chemotherapy were studied to compare the respective efficacy and safety of granisetron and metoclopramide plus dexamethasone in the prevention of nausea and vomiting induced by emetogenic cytotoxic drugs. The results showed the response rate of antiemesis in the first 24 hours was higher in the metoclopramide plus dexamethasone group than in the granisetron group: 95% vs 84%. For the next six days of the study period, the response rate of the granisetron group was shown to be more effective than that of metoclopramide plus dexamethasone group: 77% vs 60%. Furthermore, the granisetron seemed to display enhanced tolerability with less drug-related side effects and no extrapyramidal effects which appeared in 2 cases of the metoclopramide plus dexamethasone group. In conclusion, a single dose of granisetron can be as effective as the gold standard of metoclopramide plus dexamethasone regimen in preventing and treating acute nausea and vomiting. For preventing delayed nausea and vomiting, granisetron is shown to be more effective than metoclopramide plus dexamethasone.

Adult↗
PubMed1997

High dose chemotherapy with peripheral blood stem cells transplantation in patients with relapsed or refractory lymphomas preliminary reports.

High dose chemotherapy with peripheral blood stem cells transplantation (PBSCT) has been used worldwide in the treatment of patients with various hematological malignancies and other solid tumors. It has just come into use as a salvage therapy in various malignancies in Taiwan in recent years. We report eight cases with relapsed or refractory lymphoma treated with high dose chemotherapy and PBSCT. Our results showed all cases but one achieved complete remission. The mean days of white cell recovery were 10 days to > 500/microliter (ranges, 8-16 days) and 12 days to > 1,000/microliter (ranges, 9-19 days). The mean days to platelet transfusion independent, i.e. platelet > 20,000/microliters, was 14 days. No specific side effect was noted except death in one case on D+9 during cytopenia state. Four patients relapsed and died during the follow-up after PBSCT. From our preliminary results we suggest that high dose chemotherapy with PBSCT could be used as a salvage therapy in patients with relapsed or refractory lymphomas with favorable and sustained hematological recovery. Most cases were tolerable with myeloablative chemotherapy and re-achieved remission, however, remission duration was still short and relapse remained the main problem to be overcome. The long term effects of high dose chemotherapy with PBSCT still need further study.

Adolescent↗
PubMed1997

Prenatal molecular diagnosis of RET proto-oncogene mutation in multiple endocrine neoplasia type 2A.

We report a case of multiple endocrine neoplasia type 2A (MEN 2A) diagnosed prenatally at 16 weeks gestation. The 35-year-old mother is a MEN 2A patient. She had had three prior pregnancies: one resulted in a stillbirth; one produced a genetically unaffected boy; and the third was terminated in the first trimester owing to a diagnosis of blighted ovum. Autopsy did not reveal the cause of death of the stillborn infant, who was also found to be affected with MEN 2A by molecular study of paraffin-embedded tissue. Because of poor obstetric history and the patient's age, amniocentesis for cytogenetic and molecular studies was performed at 16 weeks' gestation during the pregnancy under discussion. As with other affected members in the mother's family, the missense mutation of TGC to TTC at codon 634 of the RET proto-oncogene was found in amniotic fluid cells. Analysis of DNA extracted from the lymphocytes of the infant's blood at birth confirmed the diagnosis. To our knowledge, this is the first report of prenatal diagnosis of MEN 2A.

Adult↗
PubMed1997

Intestinal obstruction after laparoscopic herniorrhaphy.

Laparoscopic herniorrhaphy is still a controversial procedure. Two cases of intestinal obstruction after laparoscopic herniorrhaphy are reported. The clinical features, possible mechanisms, managements, and outcomes were analyzed. The results showed that preexisting mesenteric defect, fibrin depositions, and longer operation time were predisposing factors for post-laparoscopic herniorrhaphy intestinal obstruction. These findings suggest that cleansing of fibrin deposition and shorter operation times may be important to avoid postoperative intestinal obstruction.

Aged↗
PubMed1996

Involvement of Phe19 in the Mn(2+)-L-malate binding and the subunit interactions of pigeon liver malic enzyme.

A triple mutant, F19S/N250S/L353Q, of pigeon liver malic enzyme was found to have no detectable enzymatic activity [Chou, W.-Y., Huang, S.-M., & Chang, G.-G. (1994) Arch. Biochem. Biophys. 310, 158-166]. In the present study, point mutants at these positions (F19S, N250S, and L353Q) were prepared by site-directed mutagenesis. Both N250S and L353Q have kinetic properties similar to those of the wild-type. On the other hand, the K(m)(app) values for both Mn2+ and L-malate of F19S were increased by approximately 10-fold, while the kcat value was decreased by 5-fold, which results in a decrease of the apparent catalytic efficiency (kcat/K(mNADP)K(mMal)K(mMn) by approximately 300-fold. These results clearly indicate that the F19S mutation is mainly responsible for the undetectable enzyme activity of the triple mutant. Three more Phe19 mutants (F19Y, F19G, and F19A) were then prepared. There is a direct correlation between the size of the substitutes and the affinities for Mn2+ and L-malate. The kinetic parameters for F19Y were similar to those for wild-type. Both F19A and F19G reveal a 5-fold decrease of kcat values. Two K(dMn) values for the high- and low-affinity sites, respectively, were detectable for the wild-type. On the contrary, only one K(dMn) value was detected for the F19 mutants, which was increased in the order of F19G > F19A > F19S > F19Y, with F19G being the most affected mutant. The K(mMal) values of F19G and F19A were increased 100- and 6-fold, respectively. The catalytic efficiency (kcat/K(mNADP)K(dMal)K(dMn)) of F19G was decreased to only 0.01% of that of the wild-type. The above results clearly indicate that the hydrophobic aromatic ring at position 19 plays a critical role in L-malate and Mn2+ binding. Furthermore, all mutants that have a small residue at position 19 exist as monomers. Therefore, Phe19 may locate in or near the regions for Mn(2+)-L-malate binding as well as for the subunit contact. These results are compatible with the asymmetric model for the quaternary structure of malic enzyme we proposed previously [Chang, G.-G., Huang, T.-M., Huang, S.-M., & Chou, W.-Y. (1994) Eur. J. Biochem. 225, 1021-1027]. The possible roles of the N-terminus of malic enzyme were also addressed.

Amino Acid Sequence↗