Biomedical subjects

C C Yang

Publications and source records attributed to C C Yang.

At least 181 records · Page 10Linked to original sources

PubMed1995

Peptide aldehyde inhibitors of hepatitis A virus 3C proteinase.

Picornaviral 3C proteinases are a group of closely related thiol proteinases responsible for processing of the viral polyprotein into its component proteins. These proteinases adopt a chymotrypsin-like fold [Allaire et al. (1994) Nature 369, 72-77; Matthews et al. (1994) Cell 77, 761-771] and a display an active-site configuration like those of the serine proteinases. Peptide-aldehydes based on the preferred peptide substrates for hepatitis A virus (HAV) 3C proteinase were synthesized by reduction of a thioester precursor. Acetyl-Leu-Ala-Ala-(N,N'-dimethylglutaminal) was found to be a reversible, slow-binding inhibitor for HAV 3C with a Ki* of (4.2 +/- 0.8) x 10(-8) M. This inhibitor showed 50-fold less activity against the highly homologous human rhinovirus (strain 14) 3C proteinase, whose peptide substrate specificity is slightly different, suggesting a high degree of selectivity. NMR spectrometry of the adduct of the 13C-labeled inhibitor with the HAV-3C proteinase indicate that a thiohemiacetal is formed between the enzyme and the aldehyde carbon as previously noted for peptide-aldehyde inhibitors of papain [Lewis & Wolfenden (1977) Biochemistry 16,4890-4894; Gamcsik et al. (1983) J. Am. Chem. Soc. 105, 6324-6325]. The adduct can also be observed by electrospray mass spectrometry.

3C Viral Proteases↗

PubMed1995

Major contribution of a carboxymethyl group to transition-state stabilization by cytidine deaminase: mutation and rescue.

The crystal structure of an inhibitory complex formed between Escherichia coli cytidine deaminase and the transition-state analog 3,4-dihydrouridine indicates the presence of a short H-bond between Glu-104 and the inhibitor. To test the possibility that analogous H-bonds might play a significant role in stabilizing the hydrated substrate in the transition state for deamination, we replaced Glu-104 by alanine. Compared with the wild-type enzyme, the mutant enzyme's affinities for substrate cytidine and product uridine were found to have increased, whereas kcat for deamination of cytidine had been reduced by 8 orders of magnitude. By its presence, the carboxymethyl group of Glu-104 appears to minimize the activation barrier for deamination, not only by stabilizing the altered substrate in the transition state but also by destabilizing the enzyme-substrate and enzyme-product complexes. In the presence of added formate ion, but not in the presence of bulkier carboxylic acids, the low catalytic activity of the mutant enzyme was enhanced substantially.

Alanine↗

PubMed1995

Sequence comparison and computer modelling of cardiotoxins and cobrotoxin isolated from Taiwan cobra.

Six cardiotoxins and one neurotoxin isolated and purified from the Taiwan cobra venom (Naja naja atra) possess distinct pharmacological and biochemical properties despite the existence of a grossly similar tertiary structure among these toxins, i. e., a core consisting of a series of short loops and four disulfide bridges. A systematic structure comparison of these major toxin isoforms was made by the secondary-structure predictions together with computer model-building based on the primary sequences and the established X-ray and NMR structures of one published cardiotoxin isoform and cobrotoxin. It is of interest to find that some defined and subtle differences can be detected upon the superposition of these three-dimensional polypeptide chains, which may reflect the intrinsic differences in the surface hydrophobicity of cardiotoxins and cobrotoxin as revealed by hydropathy profiles of these toxins in one of three major loops. The differences seem to correlate with different inhibitory activities exhibited by cardiotoxins in contrast to the lack of activity by cobrotoxin on protein kinase C (PKC).

Amino Acid Sequence↗

PubMed1995

Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with schizophrenic disorder.

As compared to normal people, the lymphocytes of patients with schizophrenia were found to have an impairment of ATP.Mg-dependent protein phosphatase activation. More importantly, the impaired protein phosphatase activation in the lymphocytes of schizophrenic patients could be consistently and completely restored to normal by exogenous pure protein kinase FA/glycogen synthase kinase-3 alpha (kinase FA/GSK-3 alpha) (the activating factor of ATP.Mg-dependent protein phosphatase), indicating that the molecular mechanism for the impaired protein phosphatase activation in schizophrenic patients may be due to a functional loss of kinase FA/GSK-3 alpha. Immunoblotting and kinase activity analysis in an anti-kinase FA/GSK-3 alpha immunoprecipitate further demonstrate that both cellular activities and protein levels of kinase FA/GSK-3 alpha in the lymphocytes of schizophrenic patients were greatly impared as compared to normal controls. Statistical analysis revealed that the lymphocytes isolated from 37 normal people contain kinase FA/GSK-3 alpha activity in the high levels of 14.8 +/- 2.4 units/mg of cell protein, whereas the lymphocytes of 48 patients with schizophrenic disorder contain kinase FA/GSK-3 alpha activity in the low levels of 2.8 +/- 1.6 units/mg, indicating that the different levels of kinase FA/GSK-3 alpha activity between schizophrenic patients and normal people are statistically significant. Taken together, the results provide initial evidence that patients with schizophrenic disorder may have a common impairment in the protein levels and cellular activities of kinase FA/GSK-3 alpha, a multisubstrate protein kinase and a multisubstrate protein phosphatase activator in their lymphocytes.

Amino Acid Sequence↗

PubMed1995

Association of protein kinase FA/GSK-3alpha (a proline-directed kinase and a regulator of protooncogenes) with human cervical carcinoma dedifferentiation/progression.

Computer analysis of protein phosphorylation-sites sequence revealed that most transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) (a particular member of PDPK family) has been optimized for human cervical tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in poorly differentiated cervical carcinoma (82.8 +/- 6.6 U/mg of protein), moderately differentiated carcinoma (36.2 +/- 3.4 U/mg of protein), and well-differentiated carcinoma (18.3 +/- 2.4 U/mg of protein) from 36 human cervical carcinoma samples when compared to 12 normal controls (4.9 +/- 0.6 U/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase FA/GSK-3alpha in cervical carcinoma is due to overexpression of protein synthesis of the kinase. Taken together, the results provide initial evidence that overexpression of protein synthesis and cellular activity of kinase FA/GSK-3alpha may be involved in human cervical carcinoma dedifferentiation/progression, supporting an association of proline-directed protein kinase with neoplastic transformation and tumorigenesis. Since protein kinase FA/GSK-3alpha may function as a possible regulator of transcription factors/proto-oncogenes, the results further suggest that kinase FA/GSK-3alpha may play a potential role in human cervical carcinogenesis, especially in its dedifferentiation and progression.

Amino Acid Sequence↗

PubMed1995

External urethral sphincterotomy: long-term follow-up.

UNLABELLED: We retrospectively reviewed the charts of 37 male spinal cord injury patients who underwent sphincterotomy from 1986-1993 to evaluate the long-term results of this procedure. Patients were selected for the operation based on urodynamic criteria and all had some detrusor activity or were able to void by Valsalva's maneuver. There were 26 cervical injuries and 11 thoracic injuries. The operation was judged a failure if the following were present postoperatively: the presence of large post void residual volumes associated with urinary tract infections, autonomic dysreflexia symptoms associated with bladder overdistension or high voiding pressures, and/or progressive upper tract deterioration due to persistent vesicoureteral reflux or poor bladder emptying. Eighteen' operations were failures and 19 operations were successful. Causes for sphincterotomy failure included recurrent detrusor sphincter dyssynergy (6), detrusor hypocontractility (6), bladder neck contracture (3), stricture at the external sphincter (1), incomplete sphincterotomy (1), and unknown etiology (1). The reoperation rate was 32%. The mean follow-up time was 49 months for the failure group (range 2-81) and 26 months (range 2-54) for the successes. The longer mean follow-up period in the former group suggests that the number of failures increased with time. There was no predictor of failure among any of the following parameters: age at operation, level of injury, previous bladder neck/sphincter operations, preoperative maximum detrusor contraction pressures, or rise time to maximum pressure. IN CONCLUSION: (1) the external urethral sphincterotomy, even in appropriately selected patients, can have a high failure rate over time, and (2) we could not identify any variables to predict an unsuccessful operation using our present selection criteria.

Adult↗

PubMed1995

Protein recognition of ammonium cations using side-chain aromatics: a structural variation for secondary ammonium ligands.

A model for the structure of dimethylamine dehydrogenase was generated using the crystal coordinates of trimethylamine dehydrogenase. Substrate is bound in trimethylamine dehydrogenase by cation-pi bonding, but modeling of dimethylamine dehydrogenase suggests that secondary amines are bound by a mixture of cation-pi and conventional hydrogen bonding. In dimethylamine dehydrogenase, binding is orientationally more specific and distinct from those proteins that bind tertiary and quaternary amine groups.

Binding Sites↗

PubMed1995

Antioxidation of human low density lipoprotein by morin hydrate.

Oxidative modification of low density lipoprotein (LDL) has been suggested to be a risk factor for the development of atherosclerosis. Agents which can protect LDL from oxidation may be useful in preventing atherogenesis. Here, we found that morin hydrate, at 100 microM concentration, effectively inhibits Cu(2+)-induced oxidation of LDL. The oxidation of LDL was assessed by agarose gel electrophoresis. This was further studied by measuring the increased values of the malondialdehyde equivalents and the decreased numbers of reactive amino groups on oxidized LDL. Trolox, at equimolar concentrations, exhibit similar effects in preventing oxidation of LDL.

Antioxidants↗

PubMed1995

Excitatory innervation of caudal hypoglossal nucleus from nucleus reticularis gigantocellularis in the rat.

We examined the possible innervation of the caudal hypoglossal nucleus by the nucleus reticularis gigantocellularis of the medulla oblongata, based on single-neuron recording and retrograde tracing experiments in Sprague-Dawley rats. Under pentobarbital sodium (50 mg/kg, i.p.) anesthesia, electrical stimulation of the caudal portion of the nucleus reticularis gigantocellularis with repetitive 0.5-ms rectangular pulses increased (46 of 51 neurons) the basal discharge frequency of spontaneously active cells, or evoked spike activity in silent, hypoglossal neurons located at the level of the obex. This excitatory effect was related to the intensity (25-100 microA) and/or frequency (0.5-20 Hz) of the stimulating pulses to the nucleus reticularis gigantocellularis. Perikaryal activation of neurons by microinjection of L-glutamate (0.5 nmol, 25 nl) into the caudal portion of the nucleus reticularis gigantocellularis similarly produced an excitatory action on eight of 14 hypoglossal neurons. Retrogradely labeled neurons were found bilaterally within the confines of the nucleus reticularis gigantocellularis following unilateral microinjection of wheatgerm agglutinin-conjugated horseradish peroxidase or Fast Blue into the corresponding hypoglossal recording sites. Furthermore, the distribution of labeled neurons in the nucleus reticularis gigantocellularis substantially overlapped with the loci of electrical or chemical stimulation. These complementary electrophysiological and neuroanatomical results support the conclusion that an excitatory link exists between the nucleus reticularis gigantocellularis and at least the caudal portion of the hypoglossal nucleus in the rat.

Amidines↗

PubMed1995

Animal study of skin resurfacing using the ultrapulse carbon dioxide laser.

Ultrapulse carbon dioxide laser ablation of rabbit skin was investigated. Macroscopic and microscopic appearance of the ablation site was evaluated for 1 month. The Ultrapulse carbon dioxide laser was set in the ultrapulse mode and the parameters selected were 250 mJ of energy per pulse and 2 W average power with the 3-mm spot size collimated handpiece. Macroscopic investigation showed that ultrapulse carbon dioxide laser ablation removed rabbit skin precisely and bloodlessly without char formation. Skin re-epithelialization without scarring and perfect hair growth restoration within 3 weeks were impressive. Microscopic investigation demonstrated a layer of tissue thermal necrosis measured as 70 +/- 10 microns. During the first 2 weeks, laser ablation wound re-epithelialization begins with multiplying epidermal layers (from 2-3 cell layers to about 13 to 15 cell layers). There were marked fibroblastic reactions and capillary congestion within papillary dermis. By the end of 4 weeks, the thickened epidermal layer appeared normal. The repaired papillary dermal collagen showed a relative compact configuration and greater cellularity in Masson stain was found 2 to 3 weeks later and also was near normal 4 weeks after laser treatment. These findings suggest that Ultrapulse's delivery of short-duration, high-energy pulses may provide a new approach (laser dermal ablation) to damage selectively the epidermis and papillary dermis of rabbit skin in one single-pulse impaction with uneventful wound healing within 1 month.

Animals↗

PubMed1995

Comparison of myocardial ischaemia in post-infarction patients with and without angina: assessment by dipyridamole 201T1 imaging.

Ninety patients with old myocardial infarction were studied to evaluate the efficacy of intravenous dipyridamole 201Tl imaging for the detection of myocardial ischaemia in post-infarction patients, and to compare the prevalence of ischaemia in 63 patients with post-infarction angina (group I) and 27 patients without angina (group II). Thirty-four of the patients in group I and 15 of the patients in group II received coronary arteriography (CAG) for comparison; these were labelled groups IA and IIA, respectively. On 201Tl imaging, the incidence of scar with ischaemia in the infarct zone and scar with ischaemia at a distance were 72% and 42% in all patients, 89% and 52% in group I vs 33% and 19% in group II (P < 0.001 and P < 0.01, respectively). On CAG testing, the rates of infarct-related recanalization vessel and multi-vessel disease were 76% and 68% in group IA vs 40% and 40% in group IIA (P < 0.05 and P > 0.05, respectively). Thus, dipyridamole 201Tl imaging is a useful modality and post-infarction angina a proper indicator in the detection of myocardial ischaemia in post-infarction patients

Adult↗

PubMed1995

Central effect of angiotensin III on caudal hypoglossal neurons in rats.

We communicated the central effect of angiotensin III (ANG III), a potent signal for extracellular dehydration, on single neurons in the caudal hypoglossal nucleus of Sprague-Dawley rats anesthetized with pentobarbital sodium. A significant number (121 of 168) of caudal hypoglossal neurons responded to intracerebroventricular application of ANG III (80 or 160 pmol), with either an increase (n = 83) or decrease (n = 38) in their spontaneous discharge. These effects of ANG III were significantly reversed by intracerebroventricular application of the nonpeptide angiotensin AT1 receptor antagonist losartan (40 nmol), but not by the AT2 antagonist, PD-123319. The hypoglossal neuronal responses to repeated administration of ANG III (80 pmol), delivered at an interval < or = 18 min, exhibited acute tachyphylaxis. Intracerebroventricular administration of the cholinergic dipsogen, carbachol (50 ng), or the osmotic stimulant, hypertonic saline (0.5 M), also elicited responses in ANG III-responsive hypoglossal neurons. These results suggest that neurons in the caudal hypoglossal nucleus may serve as the final common pathway for extracellular and, possibly, intracellular thirst in the rat. Furthermore, it is likely that the action of ANG III is mediated by the AT1 subtype of angiotensin receptors.

Angiotensin III↗

PubMed1995

Effect of intraperitoneally administered agents on human peritoneal mesothelial cell growth.

During continuous ambulatory peritoneal dialysis, the peritoneal mesothelial cell layer is under continuous sloughing and regeneration processes. Agents unfavorable for mesothelial cell growth may be harmful to the peritoneal membrane. We investigated whether frequent intraperitoneally instilled agents affect mesothelial cell growth. Peritoneal mesothelial cells were cultured from the human omentum. The proliferation was assessed by using a modified methyltetrazolium assay and confirmed by Coulter cell counting. The results showed that a high-glucose medium and heparin inhibited mesothelial cell growth. Cephalothin at the usual intraperitoneal loading and maintenance doses is toxic to mesothelial cells. Ceftazidime is toxic to mesothelial cells at its loading dose and inhibits growth at its maintenance dose. Aminoglycosides including netilmicin, gentamicin, and amikacin all had inhibitory effects at the loading and maintenance dose ranges. Vancomycin had no effect. The usual combinations of heparin and cephalothin with netilmicin or gentamicin as the initial treatment regimen for bacterial peritonitis are toxic to mesothelial cells. These results suggest that some intraperitoneal agents potentially may hamper mesothelial cell regeneration. The judicious use of heparin and the proper choice of antibiotic combinations may be warranted from the point of view of peritoneal protection.

Anti-Bacterial Agents↗

PubMed1995

An outbreak of tetrodotoxin poisoning following gastropod mollusc consumption.

Tetrodotoxin, a violent neurotoxin, is present in puffer fish and may occur in a variety of marine animals. Outbreaks of human tetrodotoxin poisoning, following consumption of marine organisms other than puffer fish, has been rare. We here report an outbreak of tetrodotoxin poisoning following ingestion of gastropod molluscs and its clinical features are discussed. A 71-year-old woman was admitted with hypertension and other neurological symptoms developing after ingestion of some molluscs. A further 16 cases were also found to have typical symptoms of tetrodotoxication after mollusc consumption. Clinical features in these 17 cases were similar to those conventionally found in tetrodotoxin poisoning, except that there was hypertension in eight cases (47%). All except one case had mild poisoning and recovered well. The molluscs consumed comprised two different species: Nassarius castus and Nassarius conoidalis, both of which were shown to contain various amounts of tetrodotoxin. It is concluded that tetrodotoxin poisoning following mollusc consumption is a possibility. Hypertension, as an unusual feature in tetrodotoxication, is frequent in this outbreak, and should be looked for in future cases. The explanation of hypertension in tetrodotoxication may come either from an exaggerated response to sympathetic stimuli, or due to various responses of the vasomotor centre to a small dose of tetrodotoxin. Further studies are required to answer this question.

Adolescent↗

PubMed1995

Severe rhabdomyolysis mimicking transverse myelitis in a heroin addict.

Heroin addiction is known to cause various medical and neurological complications. We report here a case of rhabdomyolysis following heroin abuse, in which a neurological lesion mimicking transverse myelitis was also noted. A 29-year-old man was found comatose in a kneeling position one day after a heroin overdose. On admission, he was awake, yet with total paralysis of his lower legs. Physical examination revealed marked swelling and tenderness of the four limbs, especially the lower extremities. Deep tendon reflexes and positional sense were absent in both legs; however, pin-prick sense was preserved. Transverse myelitis or spinal cord vasculitis was the initial working diagnosis. Laboratory tests disclosed significantly elevated creatinine kinase of 146289 U/L. Though suffering transient acute renal failure, his neurological abnormalities gradually improved over four weeks and a left foot drop was the only residual lesion at discharge. Rhabdomyolysis, a well defined complication following heroin use, may also cause concomitant neurological symptoms, for which careful differential diagnosis is warranted. With the increasing number of heroin addicts in Taiwan, more cases with rhabdomyolysis-induced neurological symptoms may be observed in the future.

Adult↗

PubMed1995

Metobromuron/metolachlor ingestion with late onset methemoglobinemia in a pregnant woman successfully treated with methylene blue.

Metobromuron, a substituted urea herbicide, is widely used for control of grasses and broad-leaved weeds in Taiwan. Major systemic toxicity has not been reported following poisoning. A 22-year-old woman at 36 weeks of gestation was admitted to the emergency department three hours after ingestion of a mixture of 25% metobromuron and 25% metolachlor. Though stable initially, she developed central cyanosis 12 hours later. Emergent cesarean section was considered but administration of intravenous methylene blue readily reversed the cyanosis and prevented the operation. Recurrent cyanosis did not develop. Normal vaginal delivery occurred 17 days after the poisoning. Follow-up for four years revealed normal growth of the child. Metobromuron poisoning, like other urea herbicides, may cause methemoglobinemia via its hydrolysis products. Administration of methylene blue is effective treatment and should be considered in the treatment of methemoglobinemia following urea herbicide poisoning.

Acetamides↗

PubMed1995

Hypoglycemia following ethanol ingestion in children: report of a case.

Ethanol is present in a large number of pharmaceuticals, cosmetics, detergents and beverages. Without adequate safety measures, the accidental ingestion of such products by children is possible. Ethanol ingestion by children is known to cause various metabolic and neurologic disorders, including hypoglycemia, metabolic acidosis, seizures or coma. In Taiwan, little information has been published regarding the effects of ethanol ingestion by children. This is a report of a 5-year-old boy who became hypoglycemic after ingestion of rice wine. Admitted in a coma, the boy regained consciousness within 30 min after slow administration of 5% dextrose. His initial plasma glucose level was extremely low and hypokalemia was also found. Blood ethanol was 159 mg/dL, 3 h after the alcohol ingestion. He was discharged in good health the following day. Ethanol-induced hypoglycemia may be easily overlooked as symptoms of adrenaline excess are frequently absent. Prompt recognition and treatment with intravenous glucose are essential and may be life-saving. Pediatricians need to be aware of the devastating impact of ethanol. Preventive measures, such as child-proof packaging and parent education, are required if ethanol intoxication in children is to be avoided.

Accidents, Home↗

PubMed1995

Technetium-99m albumin scintigraphy in the diagnosis of protein-losing enteropathy: a case report.

A 34-year-old female presenting with bilateral lower leg edema and distended abdomen was admitted to our hospital. The serum albumin was 1.42g/dl. Renal function and hepatic function were normal. Urinalysis did not show proteinuria. Tc-99m albumin scintigraphy was arranged for this patient to rule out protein-losing enteropathy. The results demonstrated loss of albumin into the intestines. We conclude that Tc-99m albumin scintigraphy of the abdomen is a valuable adjunct in the diagnosis of protein-losing enteropathy.

Adult↗