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Biomedical subjects

C C Huang

Publications and source records attributed to C C Huang.

At least 253 records · Page 14Linked to original sources

Short-term treatment of obesity with fluoxetine as a supplement to a low calorie diet.

BACKGROUND: Inhibitors of serotonin re-uptake including fluoxetine have generally been successful in inducing modest but statistically significant weight reductions in clinical trials. However, there are few published trials with serotonin re-uptake inhibitors in obesity therapy on Asians. This study aimed to assess the effect of fluoxetine as an adjunct therapy to a low calorie diet in the obese Taiwanese population. METHODS: Sixty healthy obese subjects [body weight > 130% of ideal body weight (IBW)] were instructed to follow a low calorie diet. All subjects were randomized to receive fluoxetine 60 mg once daily with diet or diet only for 12 weeks. RESULTS: The mean total body weight reduction at the end of the study was significantly greater in the fluoxetine group than in the diet group (mean +/- S.E., -5.75 +/- 0.69 vs. -3.06 +/- 0.59 kg, p = 0.008). The body weight reduction in the first 4 weeks and second 4 weeks were greater in the fluoxetine group and they were statistically significant (mean +/- S.E., 1st 4 weeks: -2.57 +/- 0.34 vs. -1.24 +/- 0.22 kg, p = 0.0033; 2nd 4 weeks: -1.90 +/- 0.25 vs. -0.9 +/- 0.35 kg, p = 0.0226). In the third 4 weeks, the weight reduction in the fluoxetine group was still greater, but it was not statistically significantly (mean +/- S.E., third 4 weeks: -1.21 +/- 0.34 vs. -0.73 +/- 0.25 kg, p = 0.299). More symptoms of anorexia and nausea were noted in the fluoxetine group. The other side effects noted in the fluoxetine group were usually mild and tolerable. CONCLUSION: Fluoxetine is effective, well tolerated and relatively safe in the short-term treatment of obesity in the Taiwanese population when added to a low calorie diet.

Adult↗

X-linked recessive bulbospinal neuronopathy: clinical and molecular studies in a Taiwanese family.

We describe clinical, biochemical, and molecular studies on a Taiwanese family with X-linked recessive bulbospinal neuronopathy. There were three probands and five female carriers among the 23 members examined. The clinical manifestations included progressive muscle weakness, diffuse fasciculation, postural tremor, muscle cramps, dysarthria, dysphagia, diabetes, and gynecomastia. Phenotypic expression varied among the affected subjects. Two carriers also had postural tremor and perioral fasciculation. Endocrine tests were normal except for a mild increase in serum testosterone and/or growth hormone in one patient and one carrier. Type IV hyperlipoproteinemia was observed in two patients, one carrier, and one healthy offspring. Molecular genetic studies confirmed elongation of the CAG triplet repeat in exon 1 of the gene for the androgen receptor. Sequence analysis showed that there were 42 to 43 CAG repeats in the three probands and 42 to 45 in the five carriers. The mutant allele had a tendency to increase by one or two repeats from one generation to the next. The length of CAG repeats at which the mutant allele became unstable was shorter in our family than in previous reports. The normal allele was also unstable and had a tendency to shrink by one of five repeats during transmission. These findings suggest that the number of CAG triplet repeats is variable in both the mutant and normal alleles.

Adolescent↗

The object technology framework: an object-oriented interface to molecular data and its application to collagen.

We describe the Object Technology Framework (OTF) software system developed at the University of California, San Francisco Computer Graphics Laboratory for creating C+2 classes that facilitate rapid biomolecular application development and the application of the OTF to collagen modeling. C+2 class libraries for accessing and manipulating data from standard scientific data sources can be generated using the program genlib and its class library toolkit Molecule, thereby facilitating development of new applications. Use of the OTF for generating ideal collagen structural models (gencollagen) is described. The source code for the OTF is freely available at http:/(/)www.cgl.ucsf.edu/off/ to interested application developers.

Collagen↗

Continuous venovenous hemodialysis in multiple organ systems failure patients with acute renal failure.

BACKGROUND: Continuous renal replacement therapies have become the preferable methods for treating critically ill patients with acute renal failure. We studied the use of continuous venovenous hemodialysis (CVVHD) for the management of multiple organ failure patients with acute renal failure. MATERIALS AND METHODS: Forty patients in intensive care units were studied. Their mean age was 50.5 (range 21 to 82) years. The mean of number of organ system failures per patient was 4.9 (range 4 to 6). All patients required mechanical ventilation. CVVHD was performed from the femoral vein via a double-lumen catheter. Blood flow was maintained via blood pump at rate of 120 to 150 ml/min. Bicarbonate solution was delivered to the dialysate ports of the filter at rate of 700 to 900 ml/hour. Any complications during therapy were recorded. RESULTS: The mean urea clearance was 14.7 ml/min and the mean creatinine clearance was 15.4 ml/min. Electrolytes were all within the normal ranges. There were two episodes of extracorporeal circuit blood clotting and one patient experienced hypothermia. Seven of the 40 patients (17.5%) survived. CONCLUSION: CVVHD is a safe, effective, easily established therapy for managing the multiple organ failure patients with acute renal failure, offering good metabolic, electrolyte, and fluid control.

Acute Kidney Injury↗

Endobronchial metastasis from an occult papillary thyroid carcinoma: a case report.

It is well known that occult papillary thyroid cancers can result in regional lymph node metastasis. However, this small, clinically undetectable cancer rarely causes distant metastasis; moreover, an endobronchial presentation has not been described previously. We report on a 48-year-old man who experienced hemoptysis. A fiberoptic bronchoscopic biopsy established the diagnosis of endobronchial metastasis in the absence of clinically apparent thyroid cancer. After the patient was treated with a total thyroidectomy and radioactive iodine (131I), a whole body radioiodine scan revealed no evidence of distant functioning metastasis. A histological evaluation of the thyroid gland showed the presence of a 0.2 x 0.2 x 0.2 cm nodule in the right lobe. A left pneumonectomy was undertaken to treat the distant metastasis of the disease. Since most papillary thyroid carcinomas are curable, an aggressive surgical approach to the solitary metastasis is indicated.

Bronchial Neoplasms↗

Technetium-99m-HMPAO brain SPECT in neonates with hypoglycemic encephalopathy.

Regional brain injury in three neonates with hypoglycemic encephalopathy are presented using serial 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT and, for comparison, MRI. During the acute stage, both 99mTc-HMPAO SPECT and MRI reveal abnormalities in the posterior cerebrum. Technetium-99m-HMPAO SPECT reveals further areas of insult, for example the frontal lobes. The degree of hypoperfusion correlates with the clinical severity of hypoglycemia during the neonatal period and subsequent neurological sequelae. Follow-up with HMPAO SPECT several months after insult demonstrates persistent hypoperfusion in some areas, mainly in the occipital and posterior parietal regions. MRI can depict morphological changes with superior resolution. Because morphological change generally follows slowly after functional change, MRI is less sensitive than HMPAO SPECT in detecting and predicting the extent of hypoglycemic cerebral injury during the acute phase. HMPAO SPECT during the acute stage is a valuable tool for evaluating the extent and severity of brain injury in neonates with hypoglycemic encephalopathy.

Brain↗

Generation of type-specific probes for the detection of single-copy human papillomavirus by a novel in situ hybridization method.

The integration of human papillomavirus (HPV) DNA is associated with the pathogenesis of HPV-associated malignancies. The ability, however, of standard in situ hybridization (ISH) to detect low-copy integrated HPV DNA is limited. We describe the generation of HPV type-specific biotin-labeled DNA probes and a novel ISH method that uses the catalyzed reporter deposition (CARD) system for the detection of single-copy target HPV DNA in formalin-fixed, paraffin-embedded tissue. Consensus primers flanking the noncoding region of HPVs were used to generate biotin-labeled HPV-6b, -11, -16 and -18 probes by polymerase chain reaction (PCR). The probes were used for ISH with the novel technique of CARD to increase the sensitivity of the assay. Tissue blocks were prepared from CaSki (500-600 copies of HPV-16), SiHa (1-2 copies of HPV-16), and HeLa (10-50 copies of HPV-18) cell lines, as well as from an HPV-negative cell line, C33A, and then tested to demonstrate the sensitivity and specificity of the probes. Surgical specimens were used to show the clinical applicability of this technique. We successfully detected HPV-16 DNA in CaSki and SiHa cells but not in HeLa or C33A cells. HPV-18 DNA was detected in HeLa cells but not in CaSki, SiHa, or C33A cells. Sensitivity was increased when ISH was performed using probes with more biotin incorporation or when more cycles of signal amplification were employed, but significant nonspecific background was observed after more than two cycles of signal amplification. The probes generated in this study detected specific types of HPV in surgical specimens with much higher sensitivity than did conventional ISH. We concluded that our new method was highly sensitive and could be applied to formalin-fixed, paraffin-embedded clinical material for the detection of HPV.

Carcinoma↗

Neurodevelopment of surviving infants at age two years, with a birthweight less than 2000 g and cared for in neonatal intensive care units (NICU)--results from a population based longitudinal study in Taiwan.

All surviving infants from nine neonatal intensive care units (NICU) in a southern city and county of Taiwan were followed up and assessed at 2 y of age if they had a birthweight of less than 2000 g and were born between February 1, 1993 and January 31, 1994. The assessments included: neurological, growth and general health. A comparison group of normal birthweight and full-term infants without congenital anomalies, matched by birth month and sex to the NICU survivors was also studied with respect to the same outcome measures. A developmental delay (either a severe neurological deficit or Mental Development Index < 68 or Psychomotor Development Index < 68) was present in 21 (15.4%) of the cases, compared to 3 (2.5%) of the controls (P < 0.0004). Significant correlates of developmental outcome for the cases were birthweight, gestational age, and maternal education. The very low birthweight (VLBW) children (< 1500 g) in our study cohort had a comparatively higher incidence of severe neurological deficits (and cerebral palsy) than that reported by other similar studies in developed countries. The incidence of abnormal neurodevelopmental outcome remained high in the graduates of NICU at 2 y of age, compared to that in normal controls. The findings have important implications in future health policy making regarding postnatal management of the surviving infants of NICU in developing countries such as Taiwan.

Case-Control Studies↗

Deletions of the Aequorea victoria green fluorescent protein define the minimal domain required for fluorescence.

The Green Fluorescent Protein (GFP) from the jellyfish Aequorea victoria is a widely used marker for gene expression and protein localization studies. Dissection of the structure of the protein would be expected to shed light on its potential applications to other fields such as the detection of protease activity. Using deletion analysis, we have defined the minimal domain in GFP required for fluorescence to amino acids 7-229. This domain starts at the middle of the first small alpha helix at the N terminus of GFP and ends immediately following the last beta sheet. Studies of the amino acids at both termini of the minimal domain revealed that positions 6 and 7 at the N terminus are Glu-specific. Change of the Glu residues to other amino acids results in reduction of GFP fluorescence. Position 229 at the C terminus of GFP, however, is nonspecific: the Ile can be replaced with other amino acids with no measurable loss of fluorescence. A total of only 15 terminal amino acids can be deleted from GFP without disrupting fluorescence, consistent with findings of a previous study of GFP crystal structure (Ormo, M., Cubitt, A. B., Kallio, K., Gross, L. A., Tsien, R. Y., Remington, S. J. (1996) Science 273, 1392-1395 and Yang, F., Moss, L. G., and Phillips, G. N., Jr. (1996) Nat. Biotechnol. 14, 1246-1251) that a tightly packed structure exists in the protein. We also generated internal deletions within the loop regions of GFP according to its crystal structure and found that all such deletions eliminated GFP fluorescence.

Animals↗

Automated on-line sample pretreatment system for the determination of trace metals in biological samples by inductively coupled plasma mass spectrometry.

A fully automated on-line sample pretreatment system combining microwave digestion with sample preconcentration/matrix separation for the determination of trace metals (Fe, Ni, Cu, Zn, and Pb) in blood and serum samples by inductively coupled plasma mass spectrometry (ICPMS) was designed and evaluated. The samples were mixed with an appropriate reagent and digested in a flow-through, focused microwave-heated oven. After digestion, the sample solution was transferred on-line to a column packed with iminodiacetate-based resin for separation of matrix elements like Na, K, Ca, Mg, Cl, P, and S that might interfere with the measurement by ICPMS. The analytes chelated on the resin were subsequently eluted and led to ICPMS for multielement determination. The whole sample pretreatment process was automatically controlled by a self-designed expert system. The analytical reliability of data from this on-line system was confirmed to be good with the analysis of SRM samples (Seronorm Whole Blood and NIST SRM 1598 Bovine Serum), and the limits of detection (3 sigma) for Fe, Ni, Cu, Zn, and Pb were 68, 0.34, 3.5, 13.4, and 0.22 microgram/L, respectively. With this fully automated on-line system, the determination of analytes in biological fluid samples down to micrograms-per-liter levels has been proven to be feasible, and the sample throughput can achieve up to 6 samples/h.

Animals↗

A variant form of ETS1 induces apoptosis in human colon cancer cells.

We have previously shown that the human ETS1 protein (p51-ETS1), when ectopically expressed in colon cancer cell lines, is able to reduce its tumorigenicity without affecting its growth properties. To understand the mechanism of tumor reduction, we have expressed two different forms of ETS1 in colon cancer cell lines. Data presented in this paper indicate that the naturally occurring spliced variant protein, p42-ETS1, lacking the region encoded by ETS1 exon VII, represses the tumorigenicity, while p51-ETS1 reduces the tumorigenicity. Repression of tumorigenicity mediated by p42-ETS1 appears to be caused by its ability to induce apoptosis in epithelial cancer cells. This work can have profound medical significance in that it may open up new insights into the potential role of the p42-ETS1 in the induction of apoptosis in epithelial cell cancers and may provide a rationale for its use for potential gene therapy experiments to initiate cell death in cancer cells.

Animals↗

L-deprenyl (selegiline) limits the repetitive firing of action potentials in rat hippocampal CA1 neurons via a dopaminergic mechanism.

The effects of L-deprenyl (selegiline), a highly selective monoamine oxidase type B (MAO-B) inhibitor, on cell excitability of rat hippocampal CA1 neurons were examined in slice preparations using intracellular recording techniques. Superfusion of L-deprenyl (10 and 20 microM) reversibly limited the repetitive firing (RF) of action potentials elicited by injection of depolarizing current pulses (100 ms) into the pyramidal cells. At a concentration of 1-50 microM, L-deprenyl did not alter resting membrane potential or input resistance of the hippocampal CA1 neurons. The limitation of RF by L-deprenyl (20 microM) was accompanied by the reduction of the maximal rate of rise (Vmax) of the action potentials in a non-voltage-dependent manner. In 80% of recorded cells, application of L-deprenyl (20 microM) produced an increase in the amplitude and duration of afterhyperpolarization (AHP). The limitation of L-deprenyl on RF was mimicked by other MAO-B inhibitors, pargyline and 4-phenylpyridine. In addition, the ability of L-deprenyl to limit RF was not observed in the hippocampal CA1 neurons taken from dopamine (DA)-depleted rats. Moreover, we also observed that the L-deprenyl-induced limitation of RF was specifically antagonized by (+/-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaz epine (SKF-83566, 5 microM), a selective D1 dopaminergic receptor antagonist. However, the D2 dopaminergic receptor antagonist, sulpiride (5 microM), had no effect on L-deprenyl's action. These results indicate that the MAO-B inhibitory ability leading to an increase of the dopaminergic tone in the hippocampus is involved, at least in part, in the L-deprenyl-induced reduction of neuronal excitability in the CA1 region of rat hippocampus and that the D1 dopaminergic receptor is involved in L-deprenyl's action.

Action Potentials↗

Carbachol induces inward current in rat neostriatal neurons through a G-protein-coupled mechanism.

Our recent study demonstrated that carbachol can act at M1-like muscarinic receptors to reduce the membrane K+ conductance and excite the neostriatal neurons. In the present study, we further studied the molecular mechanism by which carbachol induced inward currents in neostriatal neurons. In acutely isolated neostriatal neurons held at-60 mV, pressure application of carbachol (30 microM) induced a transient inward current underlying whole-cell voltage-clamp mode. In cells loaded with the stable GDP analogue guanosine 5'-0-(2-thiodiphosphate) (GDP-beta-S, 1 mM), the carbachol-induced inward current was significantly diminished. However, the carbachol response was not affected by intracellular dialysis of the neostriatal neurons with either protein kinase C (PKC) inhibitors, PKCI 19-36 (5 microM) or NPC-15437 (20 microM), or a potent cAMP-dependent protein kinase (PKA) inhibitor, Rp-cAMPS (25 microM). These results show that a G-protein-coupled mechanism mediates carbachol-induced inward current in the neostriatal neurons and that neither PKC- nor PKA-dependent intracellular transduction pathways are involved in the carbachol response.

Animals↗

Evidence for a catalytic role of zinc in protein farnesyltransferase. Spectroscopy of Co2+-farnesyltransferase indicates metal coordination of the substrate thiolate.

Protein farnesyltransferase (FTase) is a zinc metalloenzyme that catalyzes the addition of a farnesyl isoprenoid to a conserved cysteine in peptide or protein substrates. We have substituted the essential Zn2+ in FTase with Co2+ to investigate the function of the metal polyhedron using optical absorption spectroscopy. The catalytic activity of FTase is unchanged by the substitution of cobalt for zinc. The absorption spectrum of Co2+-FTase displays a thiolate-Co2+ charge transfer band (epsilon320 = 1030 M(-1) cm(-1)) consistent with the coordination of one cysteine side chain and also ligand field bands (epsilon560 = 140 M(-1) cm(-1)) indicative of a pentacoordinate or distorted tetrahedral metal geometry. Most importantly, the ligand-metal charge transfer band displays an increased intensity (epsilon320 = 1830 M(-1) cm(-1)) in the ternary complex of FTase x isoprenoid x peptide substrate indicative of the formation of a second Co2+-thiolate bond as cobalt coordinates the thiolate of the peptide substrate. A similar increase in the ligand-metal charge transfer band in a product complex indicates that the sulfur atom of the farnesylated peptide also coordinates the metal. Transient kinetics demonstrate that thiolate-cobalt metal coordination also occurs in an active FTase x FPP x peptide substrate complex and that the rate constant for the chemical step is 17 s(-1). These data provide evidence that the zinc ion plays an important catalytic role in FTase, most likely by activation of the cysteine thiol of the protein substrate for nucleophilic attack on the isoprenoid.

Alkyl and Aryl Transferases↗

Variations of the middle and inferior right hepatic vein: application in hepatectomy.

We evaluated the anatomic variations of the middle right hepatic vein (MRHV) and inferior right hepatic vein (IRHV) and their clinical application to the possibility of right subtotal hepatectomy. In 400 of normal livers studied with ultrasound, the IRHV was found to drain segment 6 of the liver and flow into the inferior vena cava (IVC) in 72 (18%) cases. In 22 (5.5%) cases, the MRHV was found to drain segment 5 of the liver and flow into the IVC. The size of the IRHV ranged from 0.1 cm to 0.8 cm with an average of 0.46 cm. For the MRHV, the sizes ranged from 0.1 cm to 0.9 cm with an average of 0.34 cm. In 10/79 (12.6%) cases the IRHV and in 4/ 22 (18.1%) cases the MRHV were bigger than the right hepatic vein (RHV). The distance between the RHV and IRHV ranged from 3 cm to 5 cm with an average of 3.7 cm. The distance between the RHV and MRHV ranged from 3 cm to 3.3 cm with an average of 3.1 cm. A hyperechoic edge, similar to that of the portal vein, was observed at the wall of the hypertrophic IRHV and was 0.3 cm or larger in size. Preoperative delineation of this complex venous anatomy is very important. It provides vital information in the preoperative evaluation needed before performing a right subtotal hepatectomy with preservation of segment 6 or segment 5 of the liver, and with RHV resection. Prior to undertaking a right hepatectomy, clamping the hypertrophic MRHV and IRHV electively may minimize intra-operative blood loss and extrahepatic spread of the malignancy.

Adolescent↗

Combined-modality therapy for squamous carcinoma of the buccal mucosa: treatment results and prognostic factors.

BACKGROUND: Reports on locoregional control and survival of squamous cell carcinoma of buccal mucosa are scarce in literature. In this study, a single institutions's experience of combined surgery and postoperative radiotherapy (RT) for buccal mucosal malignancy with favorable results was analyzed and presented. The prognostic factors on locoregional control were also discussed. METHODS: From January 1988 to July 1994, 57 patients with squamous cell carcinoma of buccal mucosa treated by surgery and RT were reviewed. The distributions according to American Joint Committee on Cancer (AJCC) staging were: stage II, 6; stage III, 21; and stage IV, 30 patients. Total dose of RT at the buccal area ranged from 45 Gy to 68.4 Gy, median 61.2 Gy. Tumor-related factors (AJCC stage, T stage, histologic grading, pathologic tumor invasion to skin of cheek, adjacent bony structures, and regional lymph nodes) and treatment-related factors (surgical margin, radiation dose, and the time interval between operation and RT) were analyzed to determine their influence on locoregional control. RESULTS: Three-year actuarial locoregional control rate, overall survival rate, and disease-specific survival rates were 64%, 55%, and 62%, respectively. Ten of these 22 patients (45%) with recurrent tumors were reoperated, but only 2 patients were successfully salvaged. Positive surgical margin and tumor invasion to skin of cheek were significantly poor prognostic factors on locoregional control by univariate analysis. In multivariate analysis, tumor invasion to skin of cheek was the only prognostic factor (p = .0014). CONCLUSIONS: Locoregional failure was the major cause of death for squamous buccal mucosa cancers managed with surgery and RT. Few recurrences could be detected early and successfully salvaged. Skin of cheek involvement is an important prognostic factor for buccal mucosa cancers.

Actuarial Analysis↗

Childhood-onset autosomal-dominant limb-girdle muscular dystrophy with cardiac conduction block.

We report childhood-onset autosomal-dominant limb-girdle muscular dystrophy (LGMD) in a Chinese family with complete atrioventricular conduction block in the adult members. Six patients, including 5 men and 1 woman with an age of onset from 3 to 7 years, were affected. The grandfather had exercise intolerance since childhood and complete heart block with pace-maker placement at age 52. Three siblings had proximal muscle weakness and/or wasting since age 5 and heart block in their 40s. Two grandsons at the ages 7 and 3 showed exercise intolerance, and proximal muscle weakness and wasting. Sinus bradycardia was present in the elder grandson. Muscle enzymes were elevated in 3, particularly in childhood. Muscle biopsies from the proband showed myopathic changes with fatty degeneration, whorled fibers, and rimmed vacuoles. In adult patients, muscle magnetic resonance imaging scans disclosed atrophic changes and fatty degeneration in the gluteal, quadriceps, adductors, hamstrings, gastrocnemius, and soleus muscles, while in child probands the early atrophic changes were seen in the gluteal and hamstrings muscles. We conclude that this distinct family is characterized by childhood-onset autosomal-dominant LGMD with heart block and that prevention of sudden death in these patients is important.

Adolescent↗