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Biomedical subjects

C H Ho

Publications and source records attributed to C H Ho.

At least 37 records · Page 2Linked to original sources
PubMed1999

Increased myosin light chain phosphorylation is not required for growth factor stimulation of collagen matrix contraction.

Previous research suggested the possibility that contraction of floating collagen matrices by human fibroblasts required increased myosin light chain (MLC) phosphorylation. In the current studies, we show that increased MLC phosphorylation was neither necessary for platelet-derived growth factor (PDGF)-dependent matrix contraction nor sufficient for lysophosphatidic acid (LPA)-dependent contraction. In contrast, increased MLC phosphorylation did appear to be coupled to the formation of stress fibers by cells spreading in monolayer culture. Signal transduction pathways required for PDGF- and LPA-dependent matrix contraction involved phosphatidylinositol 3-kinase and the G(i) class of heterotrimeric G proteins, respectively. Our results indicate that PDGF- and LPA-dependent contraction of floating collagen matrices can be uncoupled from an increase in MLC phosphorylation.

Actins↗
PubMed1999

A 450-kb contig of defensin genes on human chromosome 8p23.

Defensins are a large family of host defense peptides expressed in leukocytes and epithelia. Using P1 and BAC clones, we have determined the organization of the human alpha-defensin genes and the beta-defensin gene HDEFB1 on chromosome 8p23. From the telomere, the order of the genes (with encoded peptides in parentheses) is HDEFA5 (HD-5), HDEFA1/1A (HNP-1/3), HDEFA4 (HNP-4), HDEFA6 (HD-6), and HDEFB1 (HBD-1). These genes span a region of approximately 450kb. Genes encoding intestinal Paneth cell defensins (HDEFA5 and HDEFA6) flank the myeloid defensin gene cluster (HDEFA1, HDEFA1A, HDEFA4). Based on our previous studies, the remaining known defensin gene, HDEFB2 (HBD-2), is about 400kb centromeric to HDEFB1. This map supports the hypothesis, originally proposed because of sequence similarities, that myeloid alpha-defensin genes evolved by reduplication and divergence from Paneth cell defensin genes, and identifies regions and clones, which should be useful in the search for new defensin genes.

Base Sequence↗
PubMed1999

Motility of dimeric ncd on a metal-chelating surfactant: evidence that ncd is not processive.

The surface immobilization methods that allowed single-molecule motility experiments with native kinesin have not worked with the ncd motor protein and other kinesin-related motors. To solve this problem, a surfactant (Pluronic F108) was chemically modified with the metal-chelating group nitrilotriacetic acid (NTA) to allow surface immobilization of histidine-tagged microtubule motors. The chelating surfactant provided a convenient and effective method for immobilization and subsequent motility experiments with a dimeric H-tagged ncd protein (H-N195). In experiments with the absorption of H-N195 to polystyrene (PS) beads coated with F108-NTA, a monolayer of H-N195 bound in the presence of Ni2+, while in the absence of Ni2+, the extent of adsorption of H-N195 to PS beads was greatly reduced. In motility experiments with H-N195 immobilized on F108-NTA-coated surfaces, microtubules moved smoothly and consistently at an average speed of 0.16 +/- 0.01 micrometer/s in the presence of Ni2+, while without Ni2+, no microtubules landed on the F108-NTA-coated surfaces. Investigation of H-N195 motility on the F108-NTA surfaces provided several indications that ncd, unlike kinesin, is not processive. First, a critical H-N195 surface density for microtubule motility of approximately 250 molecules/micrometer(2) was observed. Second, microtubule landing rates as a function of H-N195 surface density in the presence of MgATP suggested that several H-N195 molecules must cooperate in microtubule landing. Third, the ATP KM in motility assays (235 microM) was substantially higher than the ATP KM of dimeric ncd in solution (23 microM) [Foster, K. A., Correia, J. J., and Gilbert, S. P. (1998) J. Biol. Chem. 273, 35307-35318].

Adenosine Triphosphate↗
PubMed1999

Differences in the regulation of fibroblast contraction of floating versus stressed collagen matrices.

To learn more about the regulation of contraction of collagen matrices by fibroblasts, we compared the ability of lysophosphatidic acid (LPA) and platelet-derived growth factor (PDGF) to stimulate contraction of floating and stressed collagen matrices. In floating collagen matrices, PDGF and LPA stimulated contraction with similar kinetics, but appeared to utilize complementary signaling pathways since contraction obtained by the combination of growth factors exceeded that observed with saturating concentrations of either alone. The PDGF-simulated pathway was selectively inhibited by the protein kinase inhibitor KT5926. In stressed collagen matrices, PDGF and LPA stimulated contraction with different kinetics, with LPA acting rapidly and PDGF acting only after an approximately 1-h lag period. Pertussis toxin, known to block signaling through the Gi class of heterotrimeric G-proteins, inhibited LPA-stimulated contraction of floating but not stressed matrices, suggesting that LPA-stimulated contraction depends on receptors coupled to different G-proteins in floating and stressed matrices. On the other hand, the Rho inhibitor C3 exotransferase blocked contraction of both floating and stressed collagen matrices. These results suggest the possibility that distinct signaling mechanisms regulate contraction of floating and stressed collagen matrices.

ADP Ribose Transferases↗
PubMed1999

Diagnostic and prognostic values of plasma levels of fibrinolytic markers in ovarian cancer.

OBJECTIVE: The aim of this study was to find out whether any of the fibrinolytic parameters could be used as tumor markers in predicting the prognosis of ovarian cancers. MATERIALS AND METHODS: In the present study, we determined the plasma concentrations of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), PAI-2, and uPA receptor (uPAR) in 25 patients with ovarian cancer, 16 patients with benign gynecologic tumor or inflammation, and 36 healthy controls in order to find out whether the plasma levels of these markers could be used to evaluate the prognostic value in patients with gynecologic cancers. We also determined two tissue concentrations of malignant tumor (one was at the tumor site itself and the other at the cut-end tissue of the tumor, which was expected to be free of tumor) in order to see the correlation between plasma and tissue concentrations. RESULTS: Plasma PAI-1 was significantly higher in patients with malignancy than in the healthy controls (P = 0.0001). There was no significant correlation between plasma and tissue concentrations, either tumor tissue or cut-end tissue, of the same parameters. Tissue concentrations of uPA, PAI-1, and PAI-2 were significantly higher and tPA significantly lower in the malignant tumor tissue than in the cut-end tissue in the patients with ovarian cancer (P = 0.014, 0.03, 0.002, and 0.01, respectively). Plasma PAI-1 was significantly higher in patients in the late stage of ovarian cancer than in the early stages and in the controls. CONCLUSION: From our study, we concluded that plasma levels of PAI-1 were correlated with the presence of malignant ovarian cancer and higher stage of disease.

Adult↗
PubMed1999

In vivo 31P and multilabel 13C NMR measurements for evaluation of plant metabolic pathways.

Reliable measurements of intracellular metabolites are useful for effective plant metabolic engineering. This study explored the application of in situ 31P and 13C NMR spectroscopy for long-term measurements of intracellular pH and concentrations of several metabolites in glycolysis, glucan synthesis, and central carbon metabolic pathways in plant tissues. An NMR perfusion reactor system was designed to allow Catharanthus roseus hairy root cultures to grow for 3-6 weeks, during which time NMR spectroscopy was performed. Constant cytoplasmic pH (7.40+/-0.06), observed during the entire experiment, indicated adequate oxygenation. 13C NMR spectroscopy was performed on hairy root cultures grown in solutions containing 1-13C-, 2-13C-, and 3-13C-labeled glucose in separate experiments and the flow of label was monitored. Activities of pentose phosphate pathways, nonphotosynthetic CO2 fixation, and glucan synthesis pathways were evident from the experimental results. Scrambling of label in glucans also indicated recycling of triose phosphate and their subsequent conversion to hexose phosphates.

Carbon Isotopes↗
PubMed1999

Circulating levels of thrombopoietic and inflammatory cytokines in patients with clonal and reactive thrombocytosis.

The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. To determine the relationship between endogenous cytokine levels and circulating platelet counts, we measured the serum levels of both thrombopoietic and inflammatory cytokines in the peripheral blood and bone marrow samples from 70 patients with clonal thrombocytosis (CT) caused by myeloproliferative disorders, 28 patients with reactive thrombocytosis (RT), and 35 normal control subjects. The levels of thrombopoietin (TPO), interleukin-6 (IL-6), soluble IL-6 (sIL-6) receptor, IL-11, stem cell factor (SCF), IL-3, and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA). Platelet counts were significantly higher in both CT and patients with RT (699+/-399x10(9)/L, P<.001; 642+/-200 x 10(9)/L, P<.001; respectively) as compared with the normal control subjects (240+/-47x10(9)/L). The concentrations of cytokines in the bone marrow correlated well with those in the peripheral blood. The endogenous levels of TPO, IL-6, and sIL-6 receptor were significantly higher in both CT and patients with RT than those in normal control subjects. The median level of IL-6 was significantly higher in patients with RT than in patients with CT (40 pg/mL vs. 5 pg/mL; P<.001); however, there was no detectable difference in TPO and sIL-6 receptor levels between the two groups. Significantly higher levels of SCF and IL-8 were also found in patients with CT as compared with those found in normal control subjects (median 2460 pg/mL vs 1995 pg/mL, P<.05; 20 ng/mL vs. 5 ng/mL, P = .001; respectively). Finally, IL-11 and IL-3 levels were undetectable in most patients with thrombocytosis. Our results reveal that the endogenous levels of TPO, IL-6, sIL-6 receptor, IL-8, and SCF are elevated in patients with CT or RT. These cytokines appear to be active mediators involved in the regulation of thrombopoiesis during clonal and reactive thrombocytosis.

Adult↗
PubMed1999

Methamphetamine-related deaths in San Francisco: demographic, pathologic, and toxicologic profiles.

A study was undertaken to develop demographic, toxicologic, and pathological profiles of methamphetamine-related deaths. Anatomic and toxicologic findings in 413 deaths where methamphetamine was detected were compared with findings in a control group of 114 drug-free trauma victims. The number of cases per year did not change significantly over the course of the study. Mean age was 36.8 years, but 11% were over the age of 50. Decedents were overwhelmingly male (85.2%) and Caucasian (75%). Blood concentrations of methamphetamine and amphetamine were indistinguishable in cases where methamphetamine was related to the cause of death (MR) and cases where it was not (non-MR) (2.08 vs. 1.78 mg/L, p = 0.65, and 0.217 vs. 0.19 mg/L, p = 0.82). Coronary artery disease, ranging from minimal to severe multivessel, was identified in 79 of the 413 drug users, but in only six of the 114 drug-free controls (p = 0.0004), and MR decedents had enlarged hearts compared with controls. There were also ten cases of subarachnoid and intracranial hemorrhage in the MR group. Abnormalities of the liver (34%) and lungs (24.7%) were frequent. In 65% of these cases, death was due to accidental methamphetamine toxicity. In the remaining cases, methamphetamine was an incidental finding. We conclude that, in our jurisdiction, neither the rate of detection nor the number of methamphetamine deaths has increased significantly in the past 13 years. Decedents are almost all Caucasian males, and many were approaching middle-age. Methamphetamine use is strongly associated with coronary artery disease and with subarachnoid hemorrhage.

Accidents↗
PubMed1999

Hemostatic changes in patients with liver cirrhosis.

BACKGROUND: Hemostatic changes in liver disease are complicated. An overall evaluation of the main hemostatic parameters in patients with different degrees of cirrhosis of the liver has not been reported in Taiwan. METHODS: A series of hemostatic tests and parameters including activated partial thromboplastin time, prothrombin time, thrombin time, bleeding time, factor VIII assay, antithrombin activity, fibrinogen, plasminogen, protamine sulfate test, fibrin(ogen) degradation products, D-dimer, thrombin-antithrombin complex (measured by modified antithrombin), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1, euglobulin lysis test and venous occlusion test were performed in 51 patients with cirrhosis of the liver and 33 healthy controls. Among the cirrhotics, 18 were classified as Child-Pugh group A, 16 were B and 17 were C. RESULTS: Plasminogen, antithrombin and platelet count decreased progressively, starting with group A, then B and then C, relative to the controls. Factor VIII, activated partial thromboplastin time, prothrombin time, bleeding time, D-dimer and fibrin(ogen) degradation products increased progressively starting with group A, to B and then C, relative to controls. Severity of cirrhosis correlated with hemostatic changes. No significant change in the fibrinolytic response after challenge with the venous occlusion test was found in either Child-Pugh groups A, B, C or the controls, though progressive increases in tPA were found starting with group A, to B and then C, relative to controls. CONCLUSIONS: Our study proved a close relationship between the severity of cirrhosis and hemostatic changes. Activated partial thromboplastin time was better than bleeding time or thrombin time to demonstrate the severity of liver damage and hemostatic change in cirrhosis. Because the deterioration of coagulation function and increased fibrinolytic activity paralleled the severity of liver cirrhosis, adequate treatment for cirrhotic bleeding should not only correct the coagulation defects, but should also lower the increasing fibrinolytic activity.

Adult↗
PubMed1999

Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A.

BACKGROUND: Plasma-derived factor VIII concentrates used in the treatment of hemophilia A have the potential danger of transfusion-associated viral disease. The safety and efficacy of a recombinant factor VIII preparation for the treatment of this disorder were evaluated in this study. METHODS: We compared the pharmacokinetics of plasma-derived and recombinant factor VIII in 12 previously treated subjects with severe hemophilia A. RESULTS: The recovery and elimination half-lives of the recombinant factor VIII were equal to those of plasma-derived factor VIII. It was well tolerated via parenteral therapy, and only two mild adverse reactions (5%) were reported. No evidence of new viral infection was noted during the study period with the recombinant factor VIII. CONCLUSIONS: The biologic activity of the recombinant factor VIII is comparable with that of plasma factor VIII concentrate. It is safe and efficacious for the treatment of hemophilia A.

Adult↗
PubMed1999

Acute febrile neutrophilic dermatosis (Sweet's syndrome) in hairy cell leukemia: a case report.

Sweet's syndrome is a cutaneous reactive process that is usually associated with fever, but rarely occurs in patients with hairy cell leukemia (HCL). We report the case of a patient with HCL who developed typical Sweet's syndrome five months after the diagnosis of HCL. Skin eruptions and constitutional symptoms subsided rapidly after short-term systemic adrenocorticosteroid treatment without recurrence, until the patient died from disease exacerbation and uncontrolled infection. According to his manifestations, chemical allergens, microorganisms or HCL progression were unlikely to have been the precipitating factors for development of Sweet's syndrome. Because immunologic disorders and opportunistic infection are not uncommon in patients with HCL, a skin biopsy should be taken as early as possible when cutaneous lesions and fever develop in order to establish a correct diagnosis. Hence, unnecessary and prolonged use of antibiotics is avoided and prompt relief of the symptoms by appropriate management can be achieved.

Diagnosis, Differential↗
PubMed1999

Simulation of tissue cutting and bleeding for laparoscopic surgery using auxiliary surfaces.

Realistic simulation of tissue cutting and bleeding is important components of a surgical simulator that are addressed in this study. Surgeons use a number of instruments to perform incision and dissection of tissues during minimally invasive surgery. For example, a coagulating hook is used to tear and spread the tissue that surrounds organs and scissors are used to dissect the cystic duct during laparoscopic cholecystectomy. During the execution of these procedures, bleeding may occur and blood flows over the tissue surfaces. We have developed computationally fast algorithms to display (1) tissue cutting and (2) bleeding in virtual environments with applications to laparoscopic surgery. Cutting through soft tissue generates an infinitesimally thin slit until the sides of the surface are separated from each other. Simulation of an incision through tissue surface is modeled in three steps: first, the collisions between the instrument and the tissue surface are detected as the simulated cutting tool passes through. Then, the vertices along the cutting path are duplicated. Finally, a simple elastic tissue model is used to separate the vertices from each other to reveal the cut. Accurate simulation of bleeding is a challenging problem because of the complexities of the circulatory system and the physics of viscous fluid flow. There are several fluid flow models described in the literature, but most of them are computationally slow and do not specifically address the problem of blood flowing over soft tissues. We have reviewed the existing models, and have adapted them to our specific task. The key characteristics of our blood flow model are a visually realistic display and real-time computational performance. To display bleeding in virtual environments, we developed a surface flow algorithm. This method is based on a simplified form of the Navier-Stokes equations governing viscous fluid flow. The simplification of these partial differential equations results in a wave equation that can be solved efficiently, in real-time, with finite difference techniques. The solution describes the flow of blood over the polyhedral surfaces representing the anatomical structures and is displayed as a continuous polyhedral surface drawn over the anatomy.

Algorithms↗
PubMed1999

Prevalence of factor V Leiden in the Chinese population.

BACKGROUND: Thromboembolic diseases remain a major cause of morbidity and mortality in most countries. Factor V Leiden was found to be a major cause of thromboembolic disease in Western countries. Chinese have proved to be less prone to thromboembolic diseases, therefore investigation of the prevalence of factor V Leiden is necessary among a Chinese population. METHODS: From May, 1997, to April, 1998, a total of 1,261 subjects, including 420 healthy subjects, 719 patients with nonthrombotic hematologic disorders, 77 patients with diabetes mellitus and 45 patients with deep vein thrombosis, different in age and sex, were consecutively entered into our study to determine the prevalence of factor V Leiden in the Chinese population (mean age, 50.1 +/- 18.3 years; range, 1-99 years). Of this population, 873 were male and 388 were female. RESULTS: None of the subjects was found to have factor V Leiden mutation (Arg 506-Gln mutation). Activated protein C resistance was also measured in 827 patients; none of them had an activated protein C ratio of less than 2.0. CONCLUSIONS: We suggest that factor V Leiden mutation is rare among the Chinese.

Activated Protein C Resistance↗
PubMed1998

Diagnostic and prognostic values of plasma levels of fibrinolytic markers in gastric cancer.

In the present study, we determined the plasma and tissue concentrations of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2 and urokinase-type plasminogen activator receptor in 32 patients with pathology-proved gastric cancer. The plasma levels of the same markers were compared in 37 patients with benign gastric ulcer in order to find out if these plasma levels could be used to evaluate the prognostic value in patients with gastric cancer. Plasma plasminogen activator inhibitor-1 was significantly higher in gastric cancer than in benign gastric disease (p < 0.0005), whereas plasma urokinase-type plasminogen activator was significantly lower in patients with gastric cancer than in those with benign ulcer (p = 0.003). There was no significant correlation between tissue and plasma concentrations of the same parameters. The plasma and tissue levels of fibrinolytic parameters were not affected by tumor size or distant metastasis, whereas tumor tissue concentration of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-2 were significantly higher in N0 than in N1 and N2, and tissue plasminogen activator inhibitor-1 was significantly higher in N0 than in N1. Plasma levels of the five fibrinolytic parameters could not take the place of the corresponding tissue concentrations on the diagnosis and prediction of prognosis in patients with gastric cancer. Tissue concentrations of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-2, especially the latter, can be used to predict lymph node involvement in patients with gastric cancer.

Aged↗
PubMed1998

Decreased PDGF receptor kinase activity in fibroblasts contracting stressed collagen matrices.

Fibroblasts cultured in mechanically stressed collagen matrices proliferate, whereas cells in floating collagen matrices become quiescent. Previous research indicated that one factor contributing to cell quiescence in floating matrices was reduced receptor autophosphorylation in response to PDGF stimulation (i.e., PDGF receptor desensitization). To learn more about the mechanism of PDGF receptor desensitization, we analyzed changes in PDGF receptor autophosphorylation and receptor kinase activity after stressed collagen matrices were switched to floating conditions, which results in rapid cell contraction and dissipation of mechanical stress. PDGF receptor desensitization occurred during contraction stimulated by serum but not in the absence of serum, and desensitization was prevented by inhibitors of contraction but not by inhibitors of the contraction-activated cyclic AMP signaling pathway. Receptor desensitization resulted from decreased receptor kinase activity rather than from elevated protein tyrosine phosphatase activity, and only receptors unoccupied at the time of contraction were affected. After contraction, radiolabeled PDGF binding to the cells was decreased, which suggested that receptor desensitization resulted from a contraction-dependent change in receptor availability or affinity.

Cells, Cultured↗
PubMed1998

Response times and outcomes for cardiac arrests in Las Vegas casinos.

This study was conducted to measure emergency medical services (EMS) response times in sudden out-of-hospital cardiac arrests and relate those times to probability of survival in cardiac arrest victims in Las Vegas casino-hotels from January 1993 to June 1996. Times from 911 activation to casino arrival and casino arrival to arrival at patient's side (time to first defibrillatory shock), as well as survival to hospital discharge, were studied with regression analysis. Sixty patients survived (29.3%). Response times to the hotels for survivors and nonsurvivors were similar (4.8 v 5.6 min, P = .44). However, times from arrival at the casino to arrival at the patient's side (5.0 v 6.88 min, P = .01) and elapsed times from 911 activation until first shock (9.88 v 12.46 min, P = .02) were substantially longer for nonsurvivors. Model fitting disclosed that with a 911-to-shock time of 4 minutes, survival probability was 36%. Odds decreased by 5% each minute, to 19% after 23 minutes. Ventricular fibrillation was the most common initial rhythm (187 cases) and was associated with the shortest times from 911 to shock (10.7 +/- 7.8 min). There was a strong trend to increased survival with ventricular fibrillation. The 911-to-shock times in this study are considerably better than in other published reports for large metropolitan EMS systems, but the time from 911 to shock was nearly 3 minutes longer for nonsurvivors, and even those defibrillated at 4 minutes had only a 36% chance of survival. New measures, including use of the automatic external difibrillator, to reduce the "vertical" response are urgently needed.

Cardiopulmonary Resuscitation↗
PubMed1998

Force interactions in laparoscopic simulations: haptic rendering of soft tissues.

Research in the area of computer assisted surgery and surgical simulation has mainly focused on developing 3D geometrical models of the human body from 2D medical images, visualization of internal structures for educational and preoperative surgical planning purposes, and graphical display of soft tissue behavior in real time. Conveying to the surgeon the touch and force sensations with the use of haptic interfaces has not been investigated in detail. We have developed a set of haptic rendering algorithms for simulating "surgical instrument--soft tissue" interactions. Although the focus of the study is the development of algorithms for simulation of laparoscopic procedures, the developed techniques are also useful in simulating other medical procedures involving touch and feel of soft tissues. The proposed force-reflecting soft tissue models are in various fidelities and have been developed to simulate the behavior of elastically deformable objects in virtual environments. The developed algorithms deal directly with geometry of anatomical organs, surface and compliance characteristics of tissues, and the estimation of appropriate reaction forces to convey to the user a feeling of touch and force sensations.

Algorithms↗