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Biomedical subjects

J J Hwang

Publications and source records attributed to J J Hwang.

At least 91 records · Page 5Linked to original sources
PubMed1996

Changes in S-adenosylmethionine synthetase in human liver cancer: molecular characterization and significance.

S-adenosylmethionine synthetase (SAMS) catalyzes the formation of S-adenosylmethionine (SAM) and is essential to normal cell function. There are two forms of SAMS, liver-specific and nonliver-specific (often referred to as "kidney"), which are products of two different genes. SAMS isoenzymes differ greatly in kinetic parameters and sensitivity to inhibition by methionine analogs. The current work studied changes in SAMS and their significance in liver cancer. Northern blot analysis showed that while normal liver expresses only liver-specific SAMS, both HepG2 and HuH-7 cells express only nonliver-specific SAMS. Absence of liver-specific SAMS messenger RNA (mRNA) was not because of gene deletion or rearrangement but complete lack of gene transcription. Reverse-transcription polymerase chain reaction (RT-PCR) with liver- and kidney-specific SAMS primers showed that liver-specific SAMS mRNA was absent with only kidney SAMS mRNA present in HepG2, HuH-7, Hep3B, and HuH-1 cells, and four consecutive hepatocellular carcinoma (HCC) specimens. Normal liver tissues from the same patients express both forms of SAMS mRNA. As a result of the change in SAMS expression, SAMS activity was higher in HepG2 and HuH-7 cells at physiologically relevant methionine concentrations but lower at high (mmol/L) methionine concentrations than rat hepatocytes. Treatment with ethionine and seleno-D,L-ethionine, two inhibitors known to have I50 values 50 to 60 times lower against SAMS purified from Novikoff hepatoma cells as compared with SAMS purified from normal rat liver, resulted in increased cell lysis in HepG2 and HuH-7 cells but not cultured rat hepatocytes. These agents did not affect cellular adenosine triphosphate (ATP) levels but inhibited SAMS activity in HepG2 and HuH-7 cells when added to their protein extracts. In summary, expression of SAMS is altered in human liver cancer. This occurrence may provide a potentially exploitable target for cancer chemotherapy.

Animals↗
PubMed1996

Characterization of an L-type calcium channel expressed by human retinal Müller (glial) cells.

The traditional notion that glial cells are permeable only to potassium has been revised. For example, glia from various parts of the nervous system have calcium-permeable ion channels. Since characterization of the calcium channels in glia is limited, the purpose of this study was to determine the molecular identity and examine the functional properties of a voltage-gated calcium channel expressed by Müller cells, the predominant glia of the retina. Whole-cell and perforated-patch recordings of human Müller cells in culture revealed a high threshold voltage-activated calcium current that is blocked by dihydropyridines, but not by omega-conotoxin GVIA or omega-conotoxin MVIIC. RT-PCR of cultured human Müller cells using primers specific for the calcium channel subunits demonstrated the expression of an L-type channel composed of the alpha 1D, alpha 2 and beta 3 subunits. The alpha 2 subunit of the Müller cell calcium channel is a splice variant which is distinct from either the skeletal muscle alpha 2s or the brain alpha 2b. Our electrophysiological experiments indicate that the alpha 1D/alpha 2/beta 3 calcium channel is functionally linked with the activation of a potassium channel that may serve as one of the pathways for the redistribution by Müller cells of excess retinal potassium.

Amino Acid Sequence↗
PubMed1996

Spirometry in life-long non-smoking, healthy Chinese women in Taiwan.

To establish the spirometric values for normal, healthy Chinese women in Taiwan, the spirometry of 506 life-long non-smoking, healthy Chinese women was examined, including 140 subjects over the age of 60 years. Significant correlations among age, height and forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC%, peak expiratory flow (PEF), Vmax75, Vmax50, Vmax25 were found. However, there were no significant correlations between age and FEV1/FVC%, nor age and Vmax25 in the elderly group. FEV1 (FEV1*) and FVC (FVC*) were standardized to the overall mean height for elderly women using Cole's formula. The decline in FEV1* and FVC* with age were observed. The predicted value for the average 70-year-old woman with a height of 1.5 m derived from the present study is compared with those from other surveys of the elderly. The values from the present study are somewhat higher than the values from the Hong Kong study. The authors believe the fact that all of the present subjects were life-long non-smokers might explain the differences.

Adult↗
PubMed1996

Relaxin modulates the ovulatory process and increases secretion of different gelatinases from granulosa and theca-interstitial cells in rats.

There were two related objectives in this study. The first was to determine the influence of endogenous relaxin on ovulation in rats. The second was to investigate the effect of relaxin on the secretion of gelatinases involved in extracellular matrix remodeling from rat ovarian cells. Immature rats were primed s.c. with 10 IU eCG; 51 to 52 h later, a monoclonal antibody specific for rat relaxin (MCAR), a control antibody against fluorescein (MCAF), or PBS vehicle was administered via intraovarian bursal injection under anesthesia, and 15 IU hCG was injected i.p. immediately thereafter. Rats were killed 26 h later, and oviducts were isolated and examined under the microscope to determine the number of ovulated oocytes. MCAR (0.25 and 2.5 micrograms/ovary) partially suppressed gonadotropin-induced ovulation as compared to the value for PBS controls. There was no significant difference in the number of ovulated oocytes between animals treated with MCAF and PBS controls. Also, porcine relaxin, given s.c. immediately after MCAR treatment, could reverse the inhibitory effect of MCAR on ovulation. To examine a possible mechanism for the effect of relaxin on ovulation, granulosa cells and theca-interstitial cells were obtained from ovaries of eCG-primed immature rats. The gelatinases secreted from cultured cells were analyzed using gelatin zymography and scanning densitometry. In the granulosa cell culture, relaxin increased the secretion of two major gelatinases of about 92 and 63 kDa in a dose-and time-dependent manner within 24 h of treatment. In the theca-interstitial cell culture, relaxin induced dose- and time-dependent increases in the secretion of two other major gelatinases of about 76 and 71 kDa. These gelatinases were characterized as metalloproteinases but not serine/cysteine proteinases. Furthermore, an immunoblot study demonstrated that relaxin stimulated the secretion of a 72-kDa type IV collagenase-like substance from cultured theca-interstitial cells but not from granulosa cells. This study demonstrates several original findings. First, endogenous relaxin may facilitate the ovulatory process in rats. Second, exogenous relaxin exhibits a biological effect on cultured rat theca-interstitial cells in addition to granulosa cells. Third, exogenous relaxin regulates the secretion of different major forms of gelantinases from cultured rat granulosa cells and theca-interstitial cells. The study supports the idea that relaxin may play an autocrine/paracrine role that is involved in modulating ovarian function.

Animals↗
PubMed1996

Novel retroviral vector transferring a suicide gene and a selectable marker gene with enhanced gene expression by using a tetracycline-responsive expression system.

A retroviral vector for the enhanced expression of the herpes simplex virus thymidine kinase (HSV tk) gene was developed by using a tetracycline-responsive expression system (TRES). The two components of the TRES, the chimeric transactivator (tTA) and the corresponding tTA-binding cis element (tetO), were both incorporated into a retroviral vector and resulted in high levels of tk gene expression from tetO in target cells. Amphotropic virus supernatants from stable producer cells, generated by the retroviral vector containing the TRES, gave titers of 10(4) to 10(5) G418-resistant CFU/ml on murine NIH 3T3 cells. The retroviral vector (G1tTA-[tetOTkINa]R), in which tetO was used in the opposite orientation relative to viral transcription, was capable of transducing tk and neo genes into murine NIH 3T3 cells to yield a high level of tk gene expression. TK enzyme activity in NIH 3T3 cells transduced by this vector was 417-fold higher than in control cells. This increased TK activity was returned to basal levels in the presence of tetracycline. The level of tk gene expression driven by tetO from G1tTA-[tetOTkINa]R vector in NIH 3T3 cells was fourfold higher at both the mRNA level and the TK enzyme level than that produced by the long terminal repeat of G1Tk1SvNa, the vector being used in the ongoing brain tumor gene therapy trial. Retroviral vectors containing the TRES may be useful therefore in achieving higher levels of tk gene expression, which should facilitate gene therapy approaches in the treatment of cancer.

3T3 Cells↗
PubMed1996

Interaction between T antigen and TEA domain of the factor TEF-1 derepresses simian virus 40 late promoter in vitro: identification of T-antigen domains important for transcription control.

The large tumor antigen (TAg) of simian virus 40 regulates transcription of the viral genes. The early promoter is repressed when TAg binds to the origin and DNA replication begins, whereas the late promoter is activated by TAg through both replication-dependent and -independent mechanisms. Previously it was shown that activation is diminished when a site in the viral enhancer to which the factor TEF-1 binds is disrupted. We show here that the NH2-terminal region of TAg binds to the TEA domain of TEF-1, a DNA binding domain also found in the Drosophila scalloped and the Saccharomyces cerevisiae TEC1 proteins. The interaction inhibits DNA binding by TEF-1 and activates transcription in vitro from a subset of naturally occurring late start sites. These sites are also activated by mutations in the DNA motifs to which TEF-1 binds. Therefore, TEF-1 appears to function as a repressor of late transcription, and its involvement in the early-to-late shift in viral transcription is discussed. The mutation of Ser-189 in TAg, which reduces transformation efficiency in certain assays, disrupts the interaction with TEF-1. Thus, TEF-1 might also regulate genes involved in growth control.

Animals↗
PubMed1996

Relaxin modulates human cervical stromal cell activity.

The cervix undergoes profound changes in size and consistency during pregnancy which are designed to facilitate a normal delivery. These changes are under the control of a number of hormonal factors. Experimental and clinical studies suggest that relaxin, a protein hormone, plays a role in promoting cervical softening. One possible target site for the effects of relaxin on the cervix is the stroma. In the studies reported here, cultures of normal human cervical stromal cells were used to determine what direct relaxin has on cervical cells. Relaxin at concentrations ranging from 0.10-100 ng/mL had no effect on human cervical stromal cell proliferation, but was found to modulate stromal cell activity related to the remodeling of extracellular matrix. When gelatin substrate gels were used, relaxin stimulated the secretion of several cervical stromal proteinase activities, including 36,52, and 116 kDa. Inhibitor studies using ethylenediamine tetraacetate, 1,10-phenanthroline, and L-cysteine identify these gelatinases as metalloproteinases. Neither estradiol nor progesterone augmented the effects of relaxin. A relaxin-induced concentration-dependent increase in collagenase activity was observed when measured with a conventional collagen fibril assay. Finally, relaxin was found to increase glycosaminoglycan synthesis, as indicated by [3H]g-lycocyamine incorporation in human cervical stromal cell cultures. These results indicate the relaxin may regulate cervical ripening in humans, as it does in other species, by direct effects on cervical cells.

Cell Division↗
PubMed1996

Cytokeratin fragment 19 (CYFRA 21-1) as a tumor marker in non-small cell lung cancer.

To evaluate the diagnostic value of the serum cytokeratin 19 fragment (CYFRA 21-1) in bronchogenic carcinoma, we investigated the sera of 138 patients (58 with benign pulmonary disease and 80 with non-small cell lung cancer (NSCLC)) using immunoradiometric assay. The mean (SD) value of serum CYFRA 21-1 in NSCLC (13.26 (16.54)) was significantly higher than in benign lung diseases (1.74 (1.55)) (p < 0.0001). Sensitivity for CYFRA 21-1 (using 3.5 ng/ml, a cut-off value corresponding to a 95% specificity for benign pulmonary disease) in NSCL was 62%. Positive CYFRA 21-1 levels were significantly higher in 75% of patients with squamous cell carcinoma (n = 36) than in 53% with other NSCLC (n = 44) (p < 0.05). CYFRA 21-1 levels were significantly different between squamous cell carcinoma (17.28 (19.94)) and the other NSCLC (9.96 (12.44)) (P < 0.05). Elevated CYFRA 21-1 levels in patients with stage III and IV disease (n = 64, 18.19 (26.51)) were significantly higher than in stage I and II (n = 16, 4.41 (5.76)) (p < 0.02). The positive rate of CYFRA 21-1 in tumor stage I and II was only 37%. Our results indicate that CYFRA 21-1 may be a useful tumor marker in NSCLC, especially in squamous cell carcinoma. However, CYFRA 21-1 cannot be used for the diagnosis of early stage disease of NSCLC. CYFRA 21-1 may also contribute to the monitoring of NSCLC.

Adolescent↗
PubMed1996

Pulmonary hyperinfection with Strongyloides stercoralis.

Strongyloides stercoralis is an intestinal parasite in humans. Infected patients may be asymptomatic or have mild to moderate abdominal symptoms. It may spread to the lungs and, finally, disseminate in the immunocompromised patient. S. stercoralis is an important cause of severe pulmonary infection and death in many areas of the world. Here we describe an 87-year-old man with S. stercoralis pulmonary hyperinfection. He had respiratory failure with severe abdominal distention. Chest x-ray showed infiltration over the right upper lung field. Papanicolaou stain of sputum demonstrated the rabditiform larvae of S. stercoralis. Stool examination revealed S. stercoralis larvae and eggs. He received two courses of albendazole treatment, but died 5 weeks after admission from Gram-negative bacteremia. This case is a classic presentation of the S. stercoralis pulmonary hyperinfection syndrome.

Aged↗
PubMed1995

Transesophageal echocardiographic assessment of mitral valve position and pulmonary venous flow during cardiopulmonary resuscitation in humans.

BACKGROUND: The mechanisms of blood flow during closed-chest cardiopulmonary resuscitation (CPR) in humans have been debated since the technique was first described in 1960. Two competing models, the cardiac pump theory and the thoracic pump theory, have been proposed, and some investigators have used mitral valve position during the downstroke of chest compression to distinguish between them. Previous studies using either transthoracic or transesophageal echocardiography have yielded conflicting results, and there have been few, if any, hemodynamic or echocardiographic studies on pulmonary venous flow (PVF) during CPR. METHODS AND RESULTS: In this study, transesophageal two-dimensional and pulsed Doppler echocardiography were used to study mitral valve position and flow, together with PVF, in 20 adult patients undergoing manual CPR. In the 17 patients who could be analyzed, the mitral valve closed in 5 patients (group 1) during chest compression but stayed open or opened further in the remaining 12 patients (group 2). Peak forward mitral flow occurred during the release phase in group 1 but during the compression phase in group 2. During chest compression, PVF occurred in the forward direction (from the pulmonary vein to the left atrium) in 8 of the group 2 patients (group 2a) and in the backward direction (from the left atrium to the pulmonary vein) in all group 1 patients and the remaining 4 patients in group 2 (group 2b). The downtime (time from collapse to CPR) was significantly shorter (P < .05) for those in group 1 (7.0 +/- 4.4 minutes) than in groups 2a (19.8 +/- 7.7 minutes) and 2b (17.8 +/- 6.8 minutes). CONCLUSIONS: Transesophageal echocardiography performed during manual CPR in humans disclosed three different patterns of mitral valve position and PVF during chest compression. The presence of an opened mitral valve with forward mitral flow and backward pulmonary venous flow during chest compression in a small number of subjects underscores this heterogeneity in blood flow and suggests the possible existence of a "left atrium pump" in addition to the currently known "left ventricle pump" and "chest pump" mechanisms.

Adult↗
PubMed1995

Pulmonary embolism presenting as syncope in paraplegia: a case report.

Syncope as an initial presentation of pulmonary embolism is unusual. A 16-year-old girl, with T7 paraplegia after a traumatic spinal cord injury, developed syncope on the 33rd hospital day. The episode occurred approximately 3 hours after her first tilting table training and just after her attendant had assisted passive range-of-motion exercise. Subsequent studies showed pulmonary embolism at the left lower branch of the left pulmonary artery, and the branch to lower segment of the lingual lobe. Doctors should be alert to possible diagnosis of pulmonary embolism in such high-risk patients, especially when new onset symptoms or signs appear.

Adolescent↗
PubMed1995

The evolution of platelet aggregability in patients undergoing catheter ablation for supraventricular tachycardia with radiofrequency energy: the role of antiplatelet therapy.

Forty-two consecutive patients were checked for profiles of platelet aggregability before, during, and 10 and 30 minutes after catheter ablation. They were randomized into Group A (n = 20) who accepted intravenous aspirin (in 0.015 g/kg body weight) and Group P (n = 22) who accepted only placebo treatment. Blood samples were drawn from ascending aorta (Ao) and main pulmonary artery (MPA) simultaneously at each time period. In Group P, the EC50 of substrate induced platelet aggregability decreases significantly during (for ADP, from 1.72 to 0.78 mumol/L for samples from Ao, P < 0.0001; and from 1.68 to 0.69 mumol/L for MPA, P < 0.0001; for collagen, from 2.26 to 1.34 micrograms/mL for Ao, P < 0.005, and from 2.40 to 1.64 micrograms/mL, P < 0.0001) and 10 minutes after successful ablation (for ADP, to 0.70 mumol/L for Ao, P < 0.000, and to 0.61 mumol/L for MPA, P < 0.0001; for collagen, to 1.54 micrograms/mL for Ao, P < 0.01, and to 1.63 micrograms/mL, P < 0.0001), and then returned to baseline levels 30 minutes later (all P = NS) compared with comparative baseline levels. The levels of thromboxane B2 (TXB2) had the similar evolution. The evolution of platelet aggregability profiles was not associated with total energy dose, duration of energy application, duration of procedure, impedance, and ablation site. However, there were moderate positive correlations between the TXB2 levels and tip temperatures (r = 0.56, P < 0.05 for Ao and r = 0.65, P < 0.01 for MPA). These results suggest that increased platelet aggregability can occur during and 10 minutes after radiofrequency current ablation and antiplatelet therapy can maintain "flat" response of platelet aggregability to radiofrequency energy, which may provide possible benefits in preventing the occurrence of the complication.

Adenosine Diphosphate↗
PubMed1995

Cerebral embolism from the thrombus in the atrioventricular septal aneurysm.

Atriventricular septal aneurysm is a rare finding. Thrombus within the atrioventricular septal aneurysm has never been reported. Here, we report a girl with sudden-onset hemiparesis. Magnetic resonance imaging of the patient's head revealed a lesion at the right basal ganglion. Cerebral infarction was impressed. A series of examinations was performed to find the source of the cerebral embolism. Transthoracic echocardiography further showed a thrombus in the aneurysm. A subsequent operation revealed a fresh thrombus in the aneurysm. The presence of an anatomic substrate such as this might justify anticoagulation treatment or even surgical intervention before thromboembolism occurs.

Adult↗
PubMed1995

Detection of cardiovascular shunts by transesophageal echocardiography in patients with pulmonary hypertension of unexplained cause.

The purpose of this study was to validate the usefulness of transesophageal echocardiography (TEE) in the assessment of cardiovascular shunts in patients with pulmonary hypertension (PH) of unexplained cause. Twenty-four adult patients, 16 women, 8 men; 15 to 70 years of age, with PH of unexplained cause were studied. All were examined by transthoracic echocardiography (TTE) and TEE. TTE showed the ventricular septal defect in two patients, muscular type in one and perimembranous type in the other. TEE showed the atrial septal defect in eight patients (secundum type in six and primum type in the remaining) and the patient ductus arteriosus in six patients, which were not seen by TTE. The ventricular septal defect shown by TTE was also found by TEE. Patients with a ventricular septal defect were also associated with a patient ductus arteriosus. Among 14 patients with cardiovascular lesions, nine patients displayed a pattern of bidirectional shunt, four a pure left-to-right shunt, and the remaining one a pure right-to-left shunt. All of the cardiovascular defects could be confirmed by passage of the catheter across the defect at cardiac catheterization. In light of PH, transthoracic identification of cardiovascular shunts is difficult because of the low velocity across the defect. In this study, we found that TEE was superior to TTE in detecting and localizing cardiovascular malformations in patient with PH.

Adolescent↗
PubMed1995

Left atrial spontaneous echo contrast in patients with rheumatic mitral valve disease in sinus rhythm. Implication of an altered left atrial appendage function in its formation.

Thirty-nine patients who had rheumatic mitral valve disease in sinus rhythm were studied to compare echocardiographic and hemodynamic characteristics between those with and without left atrial (LA) spontaneous echo contrast. Patients were divided into two groups according to the presence (group 1, n = 17) or absence (group 2, n = 22) of the echo contrast. Transthoracic echocardiography and transesophageal echocardiography were performed in all patients within 1 week of cardiac catheterization study. Group 1 patients (5 men and 12 women; mean age, 47.7 +/- 13.1 years) showed smaller mitral valve area, greater transmitral valve pressure gradient, and absence of moderate to severe mitral regurgitation compared with group 2 patients (7 men and 15 women; mean age, 47.8 +/- 14.3 years). There was no significant difference in LA dimension, left ventricular end-systolic and end-diastolic dimensions, or in left ventricular ejection fraction between the two groups of patients. Left atrial appendage function was studied with Doppler in 26 patients. Patients (n = 10) with LA spontaneous echo contrast had significantly lower LA appendage ejection fraction (20.34 +/- 10.76% vs 34.16 +/- 13.13%; p < 0.05) and lower LA appendage peak emptying velocity (0.17 +/- 0.09 m/s vs 0.27 +/- 0.12 m/s; p < 0.05) than those (n = 16) without echo contrast. It is concluded that obstruction to mitral flow and altered LA appendage contractile function, not the LA size, are likely to be more important factors for the development of LA and LA appendage spontaneous echo contrast in patients with rheumatic mitral valve disease (predominant mitral stenosis) who are in sinus rhythm. These findings further substantiate that blood stasis in the LA cavity and the LA appendage is the mechanism fundamental to the formation of such spontaneous echo contrast.

Adult↗
PubMed1995

Clinical significance of fibrillatory wave amplitude. A clue to left atrial appendage function in nonrheumatic atrial fibrillation.

Seventy-eight patients with chronic nonrheumatic atrial fibrillation were studied by transesophageal echocardiography with regard to the left atrial appendage function and its relation to the coarseness of atrial fibrillation on electrocardiogram. These 78 patients (52 men and 26 women; mean age, 66 +/- 10 years; range, 40 to 94 years) were classified into two groups according to the presence of coarse (group 1, n = 46; those with the greatest amplitude of fibrillatory wave in lead V1 > or = 1 mm) or fine (group 2, n = 32; those without the coarse fibrillatory wave in lead V1) atrial fibrillation on a standard 12-lead electrocardiogram within 1 month of echocardiographic studies. There were no significant differences in age, sex, mean duration of atrial fibrillation, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, and left atrial dimension between the two groups. In group 1, however, the left atrial appendage ejection fraction (24.4 +/- 14.2% vs 32.6 +/- 14.8%; p < 0.05) and the peak emptying velocity (21.7 +/- 12.6 cm/s vs 30.4 +/- 14.3 cm/s; p < 0.01) were lower than those in group 2. There were higher incidences of left atrial appendage spontaneous echo contrast (26/46 vs 7/32; p < 0.005) and thrombus (8/46 vs 0/32; p < 0.05) in group 1 patients. The coarse atrial fibrillation revealed a sensitivity of 80.0%, a specificity of 58.1%, a positive predictive value of 60.9%, and a negative predictive value of 78.1% for the presence of left atrial appendage spontaneous echo contrast and/or thrombus formation. In conclusion, in patients with coarse nonrheumatic atrial fibrillation, the left atrial appendage function is usually poor and the incidence of spontaneous echo contrast and thrombus formation appears to be higher in these patients.

Adult↗