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Biomedical subjects

C Y Hsu

Publications and source records attributed to C Y Hsu.

At least 19 recordsLinked to original sources
PubMed1992

Induction of Krox-20 expression after focal cerebral ischemia.

Krox-20 is one of the transcription factors of "zinc finger" family. The expression of Krox-20 was investigated in a rat focal cerebral ischemia model by Northern blot analysis and in situ hybridization. Northern blot analysis showed that ischemia for 30 min which caused little cortical infarction induced a 29-fold increase in Krox-20 mRNA signal exclusively in the ischemic cortex. Ischemia for 90 min which led to large cortical infarction induced Krox-20 mRNA not only in the ischemic cortex but also in the ipsilateral hippocampus. The induction of Krox-20 mRNA was rapid, transient and appeared to be controlled at the transcriptional level, as indicated by nuclear run-on assays. The regional induction of Krox-20 mRNA was further confirmed by in situ hybridization. These results suggest that the expression of transcription factor genes may play a role in the post-ischemic changes of the injured brain.

Brain Ischemia↗
PubMed1992

Inhibition kinetics and selectivity of the tyrosine kinase inhibitor erbstatin and a pyridone-based analogue.

The inhibition mechanisms of the epidermal growth factor (EGF) receptor tyrosine kinase and the cAMP-dependent kinase activities by erbstatin and its analogue, RG 14921, were studied by kinetic analysis. Both compounds were slow-binding inhibitors of the EGF receptor kinase. Erbstatin inhibited the EGF receptor kinase as a partial competitive inhibitor with respect to both ATP and the peptide substrate, suggesting that it binds at a site distinct from the ATP and peptide binding sites of the enzyme, and thus lowers the binding affinities of the enzyme for both substrates. In contrast, the analogue RG 14921 inhibited EGF receptor kinase activity as a non-competitive inhibitor with respect to both ATP and the peptide substrate. The distinct modes of inhibition by structurally related compounds suggest a dynamic and possibly extended structure of the catalytic center of the kinase domain of the receptor. Erbstatin and RG 14921 exerted similar effects on cAMP-dependent protein kinase activity. In this system, both compounds displayed potent inhibition and acted by a mode of competitive inhibition with respect to ATP and non-competitive with the peptide substrate.

Adenosine Triphosphate↗
PubMed1992

Effects of focal cerebral ischemia on inositol 1,4,5-trisphosphate 3-kinase and 5-phosphatase activities in rat cortex.

Ins(1,4,5)P3 3-kinase and 5-phosphatase are important enzymes responsible for the metabolism of Ins(1,4,5)P3, a second messenger for mobilization of intracellular Ca2+ stores. Focal cerebral ischemia induced in Long Evans rats through occlusion of the right middle cerebral artery (MCA) and both common carotid arteries resulted in a time-dependent decrease in the 3-kinase activity but not the 5-phosphatase activity. Approximately 50% of the 3-kinase activity in the cerebral cortex of the right MCA territory disappeared after 60 min of ischemia, and the enzyme activity was not restored during reperfusion. Reperfusion for 24 hr after a 60 min ischemic insult almost abolished the 3-kinase activity but the 5-phosphatase activity remained unaltered. These results suggest that the Ins(1,4,5)P3 3-kinase is one of the target enzymes of cerebral ischemia. The changes in Ins(1,4,5)P3 metabolism may be associated with the changes in intracellular Ca2+ homeostasis that underlies the pathophysiology of neuronal cell death.

Animals↗
PubMed1992

Racemization and intramolecular nucleophilic substitution reactions of ibutilide.

The kinetics and mechanisms of the racemization and cyclization reactions of ibutilide are described. The cyclization reaction yields a bell-shaped rate-pH curve consistent with a change in rate-determining step. It is hypothesized that the hydroxyl group leaves to form a carbocation intermediate; this is followed by nucleophilic attack by the amine. This mechanism is supported by kinetic analysis, aniline trapping of carbocation intermediate, and observation of all four stereo-isomers of the resulting quaternary ammonium compound. Whereas racemization can also progress through the carbocation intermediate, a direct SN2 mechanism appears to be the major route for the racemization reaction.

Anti-Arrhythmia Agents↗
PubMed1992

Receptor-linked hydrolysis of phosphoinositides and production of prostacyclin in cerebral endothelial cells.

The receptor agonist-mediated hydrolysis of phosphoinositides and production of prostacyclin were studied in murine cerebral endothelial cells (MCEC). Of 11 neurotransmitters and neuromodulators examined, carbachol, noradrenaline (NE), bradykinin, and thrombin significantly increased 3H-inositol phosphate accumulation in the presence of LiCl (20 mM). The maximal stimulation of [3H]inositol monophosphate ([3H]IP1) reached approximately 11, 11, seven, and four times the basal levels for carbachol, NE, bradykinin, and thrombin, respectively. The EC50 values of IP1 accumulation for carbachol and NE were 34 and 0.16 microM, respectively. The muscarinic antagonists, atropine and pirenzepine, blocked the carbachol-induced IP1 accumulation with Ki values of 0.3 and 30 nM, respectively. The adrenergic antagonist, prazosin, blocked NE-induced IP1 accumulation with a Ki of 0.1 nM. The calcium ionophore A23187, histamine, glutamate, vasopressin, serotonin, platelet activating factor, and substance P did not stimulate IP1 accumulation. A23187, bradykinin, and thrombin stimulated prostacyclin release to approximately four, four, and two times the basal levels, respectively, whereas carbachol and NE had little effect upon prostacyclin release. These results suggest that the activation of phospholipase C and of phospholipase A2 in MCEC are regulated separately.

Animals↗
PubMed1992

Bilateral multiple sclerosing hemangiomas of the lung.

A Chinese woman had bilateral coin lesions of the lung, which grew slowly. At pathologic examination, the lesions were considered to be multiple sclerosing hemangiomas. Multiplicity is rare, and bilaterality has not been previously reported.

Female↗
PubMed1992

Detection of localized Salmonella infection by gallium-67 citrate scan.

Fifteen cases (9 males, 6 females, ages: 18-73 y/o) of salmonella bacteremia were referred for a Gallium-67 citrate (Ga-67) scan to detect the focal site(s) of salmonella infection. Among them, 8 were finally proved to have focal infection(s). Their underlying diseases were systemic lupus erythematous (SLE, 4 cases), malignancies (2 cases), immunocompromise (1 case) and unknown disease (1 case). The focal infections detected were septic arthritis in 6, soft tissue abscesses in 4 and lung abscesses in 2. This report suggests that Ga-67 scan is of great value in detection of localized salmonella infection.

Adolescent↗
PubMed1992

[Phagocytosis of the reticuloendothelial system in diabetes mellitus].

It has been assumed that patients with diabetes mellitus (DM), who are usually susceptible to bacterial infections, have a depression of the antibacterial defense mechanism. This study was undertaken to substantiate the hypothesis that phagocytosis of the reticuloendothelial system (RES) is depressed in diabetic patients. It is believed that intravenously injected colloidal suspensions whose particles are unable to pass through the capillary barrier will be phagocytized mainly by the reticuloendothelial cells in the liver and spleen. In the present study, the RES phagocytic index (RESPI) was measured in 48 subjects: 20 normal controls and 28 patients with DM. Measurements were based on the rate of disappearance (T1/2) of radioactivity in the heart (blood pooling) after rapid I.V. injection of 3mCi of Tc-99m phytate (2mg phytate). Using a gamma camera, sequential images of the liver and heart were obtained, and computer-generated time-activity curves were established. The T1/2 was then calculated. Our results revealed that the RESPI values in the DM group were significantly increased as compared to the normal control group (normal control = 4.60 +/- 1.01; DM = 6.78 +/- 3.83; P < 0.05). This prolonged half-disappearance time of blood radioactivity in diabetic patients is interpreted as a reflection of impaired phagocytotic efficiency in the reticuloendothelial system. The results of this preliminary study add support to the in vivo evidence explaining the increased susceptibility to infection in diabetic patients.

Adolescent↗
PubMed1992

Angiodysplasia as a source of intestinal bleeding: report of seven cases.

From October 1978 to April 1991, seven patients presenting at the National Taiwan University Hospital with gastrointestinal tract hemorrhage were diagnosed by colonofibroscopy or angiography as having angiodysplasia of the colon and small intestine. There were two men and five women; their ages ranged from 23 to 65 years, with a mean age of 50.3 years. None of these patients were diagnosed by barium enema. Only two patients were diagnosed by colonofibroscopy, and six patients were diagnosed by angiography. Therefore, angiography was the most effective method for diagnosing angiodysplasia. A vascular tuft was the most frequent finding. Six patients with lesions on the right side of the colon underwent a right hemicolectomy, one patient with a lesion on the jejunum underwent a right hemicolectomy initially with segmental resection of the jejunum later. The postoperative courses were smooth, and there has been no further evidence of gastrointestinal blood loss or anemia in the follow-up period. A right hemicolectomy is the treatment of choice because these lesions are frequently multiple; the lesions are found primarily on the right side of the colon.

Adult↗
PubMed1992

The effects of hyperthyroidism on oesophageal motility.

This study, evaluating the effects of hyperthyroidism (HT) in oesophageal motility, depended on an oesophageal radionuclide transit test. A modified standard method was used to calculate: (a) total mean transit time (MTT), (b) residual fraction (RF) and (c) retrograde index (RI) in a supine position. Eighteen untreated patients with HT and 25 normal volunteers (NV) with a similar age distribution were included in this study. The results showed that oesophageal motility in patients with HT was worse than in the normal controls (P < 0.05 by Student's t-test). The correlation of MTT, RF and RI with size and function of thyroid glands in the patients with HT were calculated to explain the effects of HT in oesophageal motility. The results showed that neither the size nor the function of the thyroid glands in HT affected oesophageal motility.

Adult↗
PubMed1992

I-131 NP-59 adrenal cortical scintigraphy in suspected primary aldosteronism.

Dexamethasone suppression [Iodine-131] 6-Beta-Iodomethy1-19- Norcholesterol (I-131 NP-59) adrenal cortical scintigraphy was performed in 35 patients with suspected primary aldosteronsim, between May 1983 and June 1990. Based on clinical, biochemical, radiographic and pathologic data, the diagnostic accuracy of primary aldosteronism from I-131 NP-59 adrenal cortical scintigraphy was evaluated. The sensitivity, specificity, positive predictive accuracy and negative predictive accuracy was 78.9%, 100%, 100% and 80% respectively. We conclude that I-131 NP-59 adrenal cortical scintigraphy is an accurate and noninvasive technique for the diagnosis of suspected primary aldosteronism.

Adosterol↗
PubMed1992

Neurophysiological assessment of spinal cord and head injury.

Selected neurophysiologic studies can supplement clinical examination in assessing residual motor function after spinal cord or head injury. The ability of polyelectromyographic recording to detect subclinical suprasegmental control is illustrated in paraplegic patients after spinal cord injury. Excitatory or inhibitory modulation of segmental motor activity in a subpopulation of patients with clinically complete motor paralysis suggests residual connection across the lesion. This observation is consistent with the pathologic finding that complete transection of the spinal cord is rare after spinal cord injury. A preliminary study of motor-evoked potentials also indicates their potential value as an objective measure of the functional status of descending pathways. Neurophysiological assessment of subclinical residual motor function may be useful in understanding the role of suprasegmental input in the manifestation of spasticity, in objectively documenting recovery of function after injury, and may aid in the development of more specific restorative measures. Our limited experience in head-injured patients also suggests the potential usefulness of these tools in supplementing clinical evaluation.

Brain Injuries↗
PubMed1991

Kinetic analysis of the inhibition of the epidermal growth factor receptor tyrosine kinase by Lavendustin-A and its analogue.

Lavendustin-A was reported to be a potent tyrosine kinase inhibitor of the epidermal growth factor (EGF) receptor (Onoda, T., Iinuma, H., Sasaki, Y., Hamada, M., Isshibi, K., Naganawa, H., Takeuchi, T., Tatsuta, K., and Umezawa, K. (1989) J. Nat. Prod. 52, 1252-1257). Its inhibition kinetics was studied in detail using the baculovirus-expressed recombinant intracellular domain of the EGF receptor (EGFR-IC). Lavendustin-A (RG 14355) is a slow and tight binding inhibitor of the receptor tyrosine kinase. The pre-steady state kinetic analysis demonstrates that the inhibition corresponds to a two-step mechanism in which an initial enzyme-inhibitor complex (EI) is rapidly formed followed by a slow isomerization step to form a tight complex (EI*). The dissociation constant for the initial rapid forming complex is 370 nM, whereas the overall dissociation constant is estimated to be less than or equal to 1 nM. The difference between the two values is due to the tight binding nature of the inhibitor to the enzyme in EI*. The kinetic analysis using a preincubation protocol to pre-equilibrate the enzyme with the inhibitor in the presence of one substrate showed that Lavendustin-A is a hyperbolic mixed-type inhibitor with respect to both ATP and the peptide substrate, with a major effect on the binding affinities for both substrates. An analogue of Lavendustin-A (RG 14467) showed similar inhibition kinetics to that of Lavendustin-A. The results of the pre-steady state analysis are also consistent with the proposed two-step mechanism. The dissociation constant for the initial fast forming complex in this case is 3.4 microM, whereas the overall dissociation constant is estimated to be less than or equal to 30 nM. It is a partial (hyperbolic) competitive inhibitor with respect to ATP. Its inhibition is reduced to different extents by different peptide substrates, when the peptide is added to the enzyme simultaneously with the inhibitor. When studied with the least protective peptide, K1 (a peptide containing the major autophosphorylation site of the EGF receptor), RG 14467 acts as a hyperbolic noncompetitive inhibitor with respect to the peptide.

Adenosine Triphosphate↗
PubMed1991

Autophosphorylation of the intracellular domain of the epidermal growth factor receptor results in different effects on its tyrosine kinase activity with various peptide substrates. Phosphorylation of peptides representing Tyr(P) sites of phospholipase C-gamma.

The effect of autophosphorylation on the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) is not well understood. We previously demonstrated that phospholipase C-gamma physically associates with the EGF-activated EGFR, but not with a kinase-negative mutant of the EGFR, and, moreover, that only the tyrosine-phosphorylated EGFR is able to associate with phospholipase C-gamma. We have now investigated the effect of autophosphorylation on the tyrosine kinase activity of the EGFR by employing the purified kinase-active intracellular domain of the EGFR (EGFR-IC) produced by a baculovirus expression system. Synthetic peptides, including ones which contain the individual major tyrosine phosphorylation sites of phospholipase C-gamma, were used as substrates. We found that the extensively prephosphorylated EGFR-IC exhibited similar reaction kinetics to the unphosphorylated EGFR-IC when angiotensin II was used as a nonspecific substrate. In contrast there was a clear stimulation of kinase activity due to autophosphorylation of the EGFR-IC when peptides representing either the major autophosphorylation site of the EGFR or the EGFR phosphorylation sites of phospholipase C-gamma were used as substrates. However, the modes of stimulation for these peptides differed. The binding affinity (Km) for the unphosphorylated EGFR-IC for the peptide containing Tyr-771 of phospholipase C-gamma was relatively poor compared with other peptides, but improved 5-6-fold when the EGFR-IC was prephosphorylated. On the other hand, autophosphorylation improved the reaction velocity (Vm) of the phosphorylation of other peptides by 2-3-fold, with little or no increase in affinity. These results suggest that autophosphorylation of the EGFR may induce a conformational change of its kinase domain which enhances its kinase activity with exogenous substrates and may induce association with phospholipase C-gamma by increasing its affinity to a domain containing Tyr-771.

Amino Acid Sequence↗