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Biomedical subjects

H C Chen

Publications and source records attributed to H C Chen.

At least 289 records · Page 16Linked to original sources

Lack of influence of recombinant human erythropoietin on parathyroid function in hemodialysis patients with secondary hyperparathyroidism.

The effects of recombinant human erythropoietin (rHuEPO) treatment on parathyroid function in patients on maintenance hemodialysis (HD) with secondary hyperparathyroidism (HPT) is poorly understood. We compared the levels of serum intact parathyroid hormone (PTH) and the suppressibility of PTH by intravenous calcium infusion before and after 12 weeks of rHuEPO treatment in 8 HD patients with secondary HPT. The suppressibility of PTH by calcium infusion in HD patients was also compared with that of normal subjects. After rHuEPO treatment, in HD patients hematocrit and hemoglobin levels increased significantly from 20.1 +/- 1.3% and 6.65 +/- 0.46 g/dl to 28.7 +/- 1.0% and 9.68 +/- 0.39 g/dl, respectively. The serum intact PTH levels did not change significantly (541.9 +/- 65.3 pg/ml before versus 572.9 +/- 75.3 pg/ml after rHuEPO treatment), nor did serum ionized calcium, phosphate, magnesium, aluminum, alkaline phosphatase, and 1.25(OH)2D levels. Calcium infusion significantly increased serum ionized calcium and suppressed serum PTH levels. However, the increment in serum calcium levels and the percent decrement of serum PTH showed no significant differences before and after rHuEPO treatment in HD patients. Elevations in serum calcium levels during calcium infusions were not significantly different between normal subjects and HD patients. However, the percent maximal decrement in serum PTH level was less in HD patients both before and after rHuEPO treatment than in normal subjects (-75.4 +/- 3.9 and -76.4 +/- 4.1% versus -91.4 +/- 1.4%). We conclude that rHuEPO treatment has no influence on parathyroid function in maintenance HD patients with secondary HPT. In addition, PTH secretion is less suppressed by calcium infusion in the same group of patients.

Adult↗

Nasal adenocarcinoma with myoepithelial component in a CD-1 mouse.

Spontaneous nasal tumors are rare in mice, and only one adenocarcinoma and two more primary neoplasms of the nose have been observed in our files of long-term feeding studies, which are composed of 3,419 male and 3,521 female CD-1 (Crl:CD-1 (ICR)BR) mice. This adenocarcinoma was a 1-cm-diameter mass observed grossly in the right nasal cavity of a 454-day-old, male CD-1 mouse from a treated group in a bioassay study conducted with 340 males and 340 females. The neoplastic epithelial cells affected the normal nasal architecture on the right side of the nose. Roughly, tumor neoplastic cells of the outer, lateral portion occurred as cuboidal to low columnar cells with basilarily located nuclei and eosinophilic cytoplasm. These cells were arranged in cylindrical profiles and frequently entrapped acini of the glands of the maxillary sinus. Neoplastic epithelial cells of the inner, medial portion appeared as serous acinar or ductular structures circumscribed by multiple lagers of myoepithelial-like cells. Staining failed to demonstrate mucous secretion. The site of origin of this neoplasm appeared to be the serous glands of the maxillary sinus. The adenocarcinoma was believed to be spontaneous.

Adenocarcinoma↗

Differential pathways of insulin action upon the hepatitis B surface antigen gene expression and cell proliferation in human hepatoma cells.

We have shown previously that insulin at the physiological concentration suppresses hepatitis B surface antigen (HBsAg) gene expression in cultured human hepatoma Hep3B cells, and this suppression phenomenon is concomitant with the stimulation of cell proliferation. We have now examined whether these two distinct insulin actions on the Hep3B cells are mediated through the same or different signaling pathways. After prolonged treatment with high concentration of tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), the protein kinase C-alpha (PKC-alpha) level in the Hep3B cells was diminished and could not be detected by Western blot analysis. Under this condition, TPA treatment has no effect on the number or affinity of the insulin receptor on Hep3B cells. However, insulin-stimulated cell proliferation was completely abolished in the PKC-alpha depleted cells. In contrast, insulin still suppressed HBsAg gene expression with the same ED50 (approximately 0.5 nM) as the control cell. The induction of proto-oncogene egr-1 (early-growth-regulatory-1) by insulin and TPA under similar conditions were also examined. Both insulin and TPA stimulated egr-1 gene expression up to 10-fold in the control cell, but neither of these two agents showed any effect on egr-1 gene expression in the PKC-alpha down-regulated Hep3B cells. These observations indicate that the PKC-alpha may be involved in the insulin induced egr-1 expression and cell proliferation but not in the insulin suppressed HBsAg gene expression in human hepatoma cells.

Carcinoma, Hepatocellular↗

Jejunoileal atresia in neonates.

BACKGROUND: Jejunoileal atresia is the most common intestinal atresia and the most frequent cause of neonatal intestinal obstruction. The prognosis depends on several important factors. The patients reported were collected for evaluation of the factors contributing to their prognoses. METHODS: In the ten-year period from October 1982 to October 1992, all jejunoileal atresia patients who received treatment in this hospital were entered in this study. Possible factors contributing to prognosis, such as prematurity, low birth weight, apple peel atresia, anastomotic leakage, sepsis, short bowel syndrome were evaluated using Mann-Whitney U-test. RESULTS: Twenty-four patients of jejunoileal atresia had been managed in our hospital in 10 years period. Their ages ranged from one to thirteen days old (mean 3.9 days). The numbers and types of atresia were as follow: type I (n = 4), type II (n = 4), type IIIa (n = 10), type IIIb (n = 5), type IV (n = 1). All patients received surgical correction. Nine complications were found in eight patients, which included four anastomotic leakage, three wound infections and two intestinal obstructions. There were three mortalities from sepsis. Total parenteral nutrition was applied to 14 patients (58.3%). The mean hospital stay was 45.1 days, and the survival rate was 87.5%. Low birth weight and anastomotic leakage contributed to prolonged hospital stays (p < 0.05). CONCLUSIONS: Jejunoileal atresia is a common neonatal surgical condition. The prognosis is generally good, except when a patient presented with factors, such as, low birth weight or anastomotic leakage, which prolonged hospital stays. Moreover, sepsis is the only important factor contributing to mortality.

Female↗

Posterior urethral valves: a report of five cases.

From 1985 to 1993, five male patients with posterior urethral valves were treated at our hospital; they included three newborns, a 32-month-old and a 10-year-old child. On initial examination, all patients showed severe bilateral hydronephrosis and hydroureter on sonographic findings, dilatation of the prostate urethra and trabeculation of the bladder wall in the voiding cystourethrogram; only one patient showed vesicoureteral reflux. Type I urethral valves were present in all patients. Retrograde transurethral ablation of the valves was performed in four patients with good preoperative renal function. The postoperative courses were smooth except for vesicoureteral reflux in one patient and systemic fungus infection in another. Reimplantation of the ureter was done for the vesicoureteral reflux, and the fungus infection was treated by amphotericin B. Cutaneous vesicostomy was performed for a newborn since the urethral orifice was small. He presented with poor renal function and ascites. Delayed antegrade ablation of the valves per vesicostomy and closure of the vesicostomy were done three months later after restoration of the renal function. Renal function returned to normal after operation in all patients, but the function of the upper urinary tract and bladder continence need long-term follow-up.

Child↗

Stimulation of phosphatidylinositol 3'-kinase association with foca adhesion kinase by platelet-derived growth factor.

We have previously described the stable association of the focal adhesion kinase (FAK) with phosphatidylinositol 3'-kinase (PI3K) in NIH 3T3 cells. This interaction was stimulated by cell adhesion in vivo and by autophosphorylation of recombinant FAK in vitro. In this report, we show that platelet-derived growth factor (PDGF) could also specifically stimulate this association in vivo. This stimulation is independent of cell adhesion or the integrity of the cytoskeleton, suggesting potentially different mechanisms by which the cell surface PDGF receptor and integrins regulate PI3K:FAK associations. We also found that this increased association in response to PDGF occurred in the membrane fractions, consistent with the recruitment of PI3K to the cell surface by the activated PDGF receptor. These results provide a novel mechanism of cross-talk between the signaling pathways initiated by PDGF and that initiated by integrins and raise the intriguing possibility that FAK might participate in some of the cellular effects of the growth factors in modulating cell morphology and migration.

3T3 Cells↗

Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase.

The focal adhesion kinase (FAK) has been implicated in signal transduction pathways initiated by cell adhesion receptor integrins and by neuropeptide growth factors. To gain insight into FAK function, we examined the potential interaction of FAK with intracellular signaling molecules containing the Src homology 2 domains. We report here the stable association of FAK with phosphatidylinositol 3-kinase (PI3-kinase; EC 2.7.1.137) in NIH 3T3 mouse fibroblasts. This interaction was stimulated by cell adhesion concomitant with FAK activation. We also found that recombinant FAK bound to the p85 subunit of PI 3-kinase directly in vitro and that autophosphorylation of recombinant FAK in vitro increased its binding to PI 3-kinase. We detected increased tyrosine phosphorylation of the p85 subunit of PI 3-kinase during cell adhesion and observed direct phosphorylation of p85 by FAK in vitro. Together, these results suggest that PI 3-kinase may be a FAK substrate in vivo and serve as an effector of FAK.

3T3 Cells↗

Aggregation of beta A3-crystallin is independent of the specific sequence of the domain connecting peptide.

The beta- and gamma-crystallins are structural proteins whose high concentration and close packing are important in maintaining transparency of the eye lens. The beta gamma-crystallin superfamily includes proteins with similar core structures consisting of two compact domains linked by a short connecting peptide. In gamma-crystallins, the connecting peptide folds back on itself, allowing the amino and carboxyl domains to participate in close interactions. The beta-crystallin connecting peptide is extended so that dimerization of two beta-crystallin monomers is required for similar interdomain interactions. In order to examine the role of the sequence of the connecting peptide in determining the extended beta-crystallin conformation and hence their association into dimers, we have exchanged the 10 residues of the beta A3-crystallin connecting peptide with the 9-residue connecting peptide sequence of mouse gamma B-crystallin by site-directed mutagenesis. Unaltered and modified recombinant beta A3-crystallins were expressed in a baculovirus system and purified by sequential anion exchange chromatography and gel filtration. Integrity of the recombinant crystallins was confirmed by NH2-terminal sequence analysis, immunoblots, and CD spectrometry. Reconstitution of the mutant recombinant protein with crystallins from mouse lens soluble extract resulted in aggregates of identical size distribution as normal beta A3-crystallin. We conclude that the sequence of the connecting peptide is not critical for the association of beta A3-crystallin into dimers and higher order aggregates as had been postulated.

Amino Acid Sequence↗

Crystallization and preliminary X-ray analysis of GAP 31. A protein which inhibits the life cycle of HIV-1.

GAP 31 is an anti-HIV plant protein that we have identified and purified to homogeneity from Gelonium multiflorum. It is the first reported example of an anti-HIV agent capable of acting against multiple stages of the viral life cycle, on viral infection and viral replication. GAP 31 is a unique paragon of multi-functional protein. In addition to anti-HIV activity, it also exhibits anti-tumor action, DNA binding, RNA binding and ribosome inactivation. The present crystals diffract up to 2.0 A resolution and belong to monoclinic space group P2(1). The cell dimensions are a = 49.30(2) A, b = 44.57(2) A, c = 137.78(7) A and beta = 98.32(3) degrees. There are two molecules of molecular weight 31 kDa in an asymmetric unit with a solvent content of 49%.

Antiviral Agents↗

A rapid method for detection of N-acetylglucosaminidase-type chitinase activity in crossed immunoelectrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels using 4-methylumbelliferyl-N-acetyl-D-glucosaminide as substrate.

A method for the detection of N-acetylglucosaminidase (GlcNAcase) activity has been developed by using 4-methyl-umbelliferyl-N-acetyl-D-glucosaminide (4-MU-GlcNAc) as substrate in crossed immunoelectrophoresis (CIE) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels. Visualization of the reaction with a 366 nm ultra-violet light is possible in approximately 30 min. The method is fast and sensitive in comparison with previous methods. The same band as in SDS-PAGE, showing both GlcNAcase and chitinase activity, was found in the present study; we therefore conclude that this method is also useful in a GlcNAcase-type chitinase assay.

Acetylglucosamine↗

Distal phalanx replantation.

Microsurgical replantation has been attempted in the distal phalanx of the digits. Twenty-three complete, single digit amputations are reviewed. The patients' ages ranged from 9 months to 48 years. Viability was 78%. Sensory recovery averaged 7 mm static two-point discrimination. Range of motion in the distal interphalangeal joint of the finger and the interphalangeal joint of the thumb averaged 64 and 51 degrees, respectively. Eight of the 17 successfully replanted digits had mild to moderate atrophy. Eighty-two percent of patients were able to use the replanted digit successfully in their daily work. We feel that distal digital replantation is rewarding. In successful cases, it always preserves acceptable function and good appearance at a price of an average of 2.3 months off work.

Adolescent↗

Major mandibular reconstruction with vascularized bone grafts: indications and selection of donor tissue.

Free vascularized bones have been shown by many specialists to exhibit specific capabilities of reconstructing a major mandibular defect and can solve problems that may be insoluble by other methods. Nevertheless, absolute indications for using vascularized bone for major mandibular reconstructions have not been sufficiently well delineated to convince people of always considering vascularized bone for major mandibular reconstructions as a first option. Based on our experience with 55 major mandibular reconstructions, we might delineate the absolute indications for using free vascularized bone for major mandibular reconstructions explicitly: 1) osteoradionecrosis of mandible or on irradiated tissue bed; 2) hemimandibular reconstruction with a free end facing the glenoid fossa; 3) long segment mandibular defect, especially across the symphysis; 4) inadequate skin or mucosal lining; 5) defects demanding sandwich reconstruction; 6) inability to obtain secure immobilization on the reconstructed unit; 7) failure of reconstruction by other methods; 8) near total mandibular reconstruction. Selection of donor tissue should be according to 1) the amount of tissue deficiencies, 2) composition of the defect, 3) design and placement of the flap, 4) irradiation on the recipient site or not, 5) which vessels to be used, 6) which flap has the appropriate vessel length 7) skin color and texture of the donor tissue, 8) how many osteotomies required to stimulate the curvature of the resected mandible 9) speed of bony union, 10) feasibility of future osseointegration. We have used three kinds of vascularized bones (iliac bone, fibula, scapula). Iliac bone was most frequently used, and has always been our first choice, since it can carry good quality bone, a large skin flap, and ample soft tissue. The fibula has the merit of being less bulky and good for simultaneous intraoral lining, but the contour is more rigid and the bony height is insufficient. The scapula bone is rarely used at present because of its relative inconvenience.

Adult↗

Selection of recipient vessels for free flaps to the distal leg and foot following trauma.

The recipient vessels are of prime importance in free flap transfers to the lower limbs. To determine the incidence and pattern of vascular trauma, a study was carried out in 126 patients who had Gustillo Type III open fractures of the distal legs and feet that required free flaps for wound coverage. In comparison with the posterior tibial artery, the anterior tibial artery has a much higher incidence of injury with more extensive damage. It can be injured at a more proximal level than estimated from gross inspection during surgery. This should be borne in mind when the anterior tibial artery is selected as the recipient artery in order to prevent reexploration and failure of the flaps. However, the posterior tibial artery is much less vulnerable to damage in most injuries and is more reliable as the recipient artery. In this series there was no problem in finding proper recipient veins in the legs. A general principle is proposed for selecting recipient vessels in crushed legs, with a warning against the pitfalls that have been encountered.

Adolescent↗

A surface mutant (G82R) of a human alpha-glutathione S-transferase shows decreased thermal stability and a new mode of molecular association in the crystal.

A chimeric enzyme (GST121) of the human alpha-glutathione S-transferases GST1-1 and GST2-2, which has improved catalytic efficiency and thermostability from its wild-type parent proteins, has been crystallized in a space group that is isomorphous with that reported for crystals of GST1-1. However, a single-site (G82R) mutant of GST121, which exhibits a significant reduction both in vitro and in vivo in protein thermostability, forms crystals that are not isomorphous with GST1-1. The mutant protein crystallizes in space group P2(1)2(1)2(1), with cell dimensions a = 49.5, b = 92.9, c = 115.9 A, and one dimer per asymmetric unit. Preliminary crystallographic results show that a mutation of the surface residue Gly 82 from a neutral to a charged residue causes new salt bridges to be formed among the GST dimers, suggesting that the G82R mutant might aggregate more readily than does GST121 in solution, resulting in a change of its solution properties.

Amino Acid Sequence↗

The acute effect of smoking on retinal blood flow in subjects with and without diabetes.

PURPOSE: This study investigates the effect of smoking on retinal blood flow and autoregulation in smokers with and without diabetes. METHODS: Eleven patients with diabetes mellitus and ten control subjects were investigated. Laser Doppler velocimetry and retinal photography were used to measure retinal blood flow; vascular autoregulation was assessed with 60% oxygen breathing. These procedures were performed before and after smoking. RESULTS: Both groups demonstrated a significant increase in heart rate and systolic and diastolic blood pressure (P < 0.01). In both groups, smoking caused a significant decrease in retinal blood flow: 9.6% +/- 12% in the control group (P < 0.05) and 16.4% +/- 13.8% in the diabetic group (P < 0.01). The pre-smoking oxygen reactivity was comparable in both groups (P = 0.5); 27.9% +/- 3.3% and 32.0% +/- 5.0% in the control and diabetic groups, respectively. After smoking, oxygen reactivity was reduced significantly in the control group to 9.6% +/- 4.0% (P = 0.002) and eliminated in the patients with diabetes. CONCLUSIONS: This study shows that smoking reduces retinal blood flow and the ability of the retinal vessels to autoregulate to hyperoxia; these effects are likely to be due to the vasoconstrictive effect of nicotine, which is mediated through activation of the sympathetic system. Smoking has been shown previously to increase the level of carboxyhemoglobin, thereby reducing the oxygen-carrying capacity of blood, which, when associated with the reduced blood flow shown in the current study, may reduce retinal oxygen delivery. Hypoxia is a major factor in the progression of diabetic retinopathy; therefore, smoking may exert a detrimental influence, which may be compounded further by the additional effect smoking has on autoregulation.

Adult↗

Effect of betaxolol on the retinal circulation in eyes with ocular hypertension: a pilot study.

This study investigated the effect of betaxolol, a beta 1 selective blocker, on the retinal circulation in 10 patients with ocular hypertension. In a masked randomised fashion, one eye of each subject received betaxolol and the fellow eye received placebo (hypromellose). Retinal blood flow (RBF) was determined in a major temporal vein of each eye just prior to instillation of drops and 2 h later, using laser Doppler velocimetry and monochromatic fundus photography. There was an increase of 15.0% in RBF (p = 0.03) in the betaxolol-treated eyes. No significant change was observed in the placebo-treated eyes. Intraocular pressure was reduced by 27.7% in the treated eyes, resulting in an increase of 16.9% in perfusion pressure (p = 0.02) compared with an 8.4% increase in placebo-treated eyes (p = 0.15). This study demonstrated that betaxolol increases RBF in eyes with ocular hypertension; this increase is probably related to the increase in perfusion pressure.

Administration, Topical↗

Vessel diameter changes during the cardiac cycle.

Retinal vessel diameter, which is an important parameter in blood flow measurement, is affected by pulsation during the cardiac cycle and by vasomotion. This project studied these changes by analysing three monochromatic fundus photographs taken in eight arbitrary parts of the cardiac cycle of 10 healthy subjects. It was found that the venous diameter decreased in early systole, increasing thereafter to a maximum level in early diastole and then declined towards end diastole. The maximum change of 4.82% (between early systole and early diastole) (p = 0.03) represents a 9.83% change in volumetric blood flow. The arterial diameter peaked in mid-late systole, increasing by 3.46% (p = 0.01); this represents a blood flow increase of 7.04%. Vasomotion led to changes of 3.71% and 2.61% in arteries and veins respectively. It is concluded that for accurate measurement of retinal blood flow, fundus photographs should be taken synchronised with the electrocardiogram.

Adult↗

Induction of heparin-binding epidermal growth factor-like growth factor mRNA by protein kinase C activators.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent smooth muscle cell mitogen of macrophage origin. To determine whether the HB-EGF gene is transcribed and regulated in mesangial cells, we measured HB-EGF mRNA levels in cultured rat mesangial cells by RNA blot analysis. A 2.5-kb HB-EGF mRNA was detected in unstimulated mesangial cells. The protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) increased HB-EGF mRNA levels by 15-fold in mesangial cells, and this induction of HB-EGF mRNA by TPA was both time- and dose-dependent. HB-EGF mRNA could also be stimulated by 10% fetal calf serum, ionomycin, thrombin, and endothelin-1. Staurosporine, a protein kinase C inhibitor, abolished the induction of HB-EGF mRNA by TPA and serum. To determine whether HB-EGF is mitogenic for mesangial cells, we transfected COS cells with HB-EGF expression plasmids. Culture medium from COS cells transfected with these plasmids increased 3H-thymidine incorporation in mesangial cells in a dose-dependent manner. To our knowledge, this is the first report that HB-EGF is expressed in renal cells. This inducible transcription of HB-EGF suggests that it may have an autocrine role in mesangial cell proliferation in kidney disease.

Alkaloids↗