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Biomedical subjects

M C Lin

Publications and source records attributed to M C Lin.

At least 127 records · Page 7Linked to original sources
PubMed1998

Hepatic resection for bilobar multicentric hepatocellular carcinoma: is it justified?

BACKGROUND: Hepatic resection for multiple hepatocellular carcinomas (HCCs) involving both lobes of the liver is rarely recommended because of high operative risks and low radicality. Thus the justification of hepatic resection for bilobar multicentric HCC remains undefined. METHODS: Two hundred eleven patients with HCC, who underwent curative hepatic resection, were studied retrospectively. The patients were divided into two groups. Group A consisted of 39 patients with bilobar (both sides of Cantlie's line) multicentric HCCs. Group B consisted of 172 patients with HCC with solitary or unilobar lesions. The backgrounds and resectional results of patients in groups A and B were compared. RESULTS: Patients in group A usually required multiple separate liver resections and a longer operative time. However, the operative blood loss, amount of blood transfused, and operative morbidity and mortality rates were not significantly different. Patients in group A showed higher incidences of associated satellite nodules, microscopic vascular invasion, and a lack of capsules. The 6-year disease-free and actuarial survival rates of patients in groups A and B were 30.5% and 41.8% (p = 0.17) and 42.9% and 51.4% (p = 0.12), respectively. For patients in group A the presence of satellite nodules in any resected tumor was the only independent unfavorable feature that influenced the actuarial survival rate after multivariate analysis. CONCLUSIONS: Liver resection is justified for bilobar multicentric HCCs in selected patients, if the tumors can be totally resected. Postoperative adjuvant therapies should be considered when satellite nodules are present in any resected tumor.

Adult↗
PubMed1998

Patterns of allelic loss (LOH) in vulvar squamous carcinomas and adjacent noninvasive epithelia.

The pathogenesis of carcinoma of the vulva is diverse and includes both human papilloma virus (HPV)-positive and HPV-negative pathways. The objective of this study was to correlate the morphology with patterns of loss of heterozygosity (LOH) within four vulvar carcinomas and in adjacent vulvar epithelia. Tumors were categorized as HPV positive or negative by polymerase chain reaction (PCR) analysis. Forty-one different sites of normal squamous mucosa, hyperplasia, vulvar intraepithelial neoplasia (VIN), and carcinoma were microdissected in duplicate, and each extracted DNA was analyzed in duplicate for LOH at 10 chromosomal loci by PCR and polyacrylamide gel electrophoresis. Patterns of LOH were compared within different sites of tumors and between the tumor and the noninvasive epithelia. Of three tumors with multiple invasive foci analyzed, divergent patterns of LOH were identified in two, correlating in one with differences in tumor grade. In one HPV-16-positive case, multiple sites of VIN displayed heterogeneity for LOH consistent with divergent clonal or subclonal populations, some of which were not shared by the tumor. In one HPV-negative case, LOH was found in foci of hyperplasia and differentiated VIN (atypical hyperplasia), the latter sharing LOH with the invasive carcinoma at some but not all chromosomal loci. This study suggests that a genetic relationship exists between VIN and carcinoma, irrespective of HPV involvement. It also suggests that in HPV-negative tumors, allelic loss may predate the onset of invasive carcinoma and, in some cases, cellular atypia (VIN). However, the divergent patterns of LOH observed imply that many genetic alterations in the adjacent vulvar epithelium are not directly related to the invasive carcinoma.

Carcinoma in Situ↗
PubMed1998

Serodiagnosis of tuberculosis by enzyme-linked immunosorbent assay for anti-A60 and anti-A38.

BACKGROUND: For early diagnosis of tuberculosis (TB), especially in the patients without adequate sputum specimens for examination, we found a simple, rapid and inexpensive method among many current available diagnostic tools, the enzyme-linked immunosorbent assay (ELISA). To investigate the diagnostic effectiveness of this method, we applied ELISA for detection of antigen 60 IgG and IgM as well as antigen 38 IgG antibodies at Chang Gung Memorial Hospital from April 1995 through June 1996. MATERIALS AND METHODS: Sixty-seven patients were enrolled and divided into 3 groups, Group A (n = 24), patients with positive sputum acid-fast stain; Group B (n = 18), patients with lung cancer and negative sputum acid-fast stain; and Group C (n = 25), patients with chest roentgenogram (CXR) which were suggestive of TB but with negative acid-fast stain results or no sputum for examination. RESULTS: For the A60 IgG antibody, we found a sensitivity rate of 91.7% for Group A and Group B, and 85.7% for Group C as well as an overall sensitivity of 89.5% but with lower specificity. For the A60 IgM antibody, a lower sensitivity (37.5%, 14.3%, 28.9%, respectively) was found but with higher specificity. For the A38 IgG antibody, we found a lower sensitivity (40%, 11.1%, 31%, respectively) but with higher specificity (100%, 71.4%, 90%, respectively). CONCLUSION: With a high sensitivity but low specificity for diagnosis of TB, A60 IgG ELISA could be used as a rapid, simple screening test for patients with results suggestive of TB, especially in those who had no sputum or had negative sputum acid-fast stain results. Otherwise, A60 IgM or A38 IgG ELISA, with a high specificity, could be used as a reliable test in the diagnosis of pulmonary TB when the result is positive. In summary, although ELISA is a simple, rapid, inexpensive method, it is helpful but limited in the diagnosis of pulmonary TB.

Antibodies, Bacterial↗
PubMed1997

Activation volume of DNA duplex formation.

The denaturation-renaturation thermal hysteresis was used to investigate the kinetics of the helix-coil equilibrium of four 22-base pair homopurine-homopyrimidine duplex oligonucleotides with fractional G x C base pair content (f(G x C)) between 0.14 and 0.5. In 20 mM NaCl and 20 mM Tris-HCl at pH 7.0 and at hydrostatic pressures up to 200 MPa, a two-state bimolecular reaction mechanism adequately described the observed kinetics. At 1 MPa and 47 degrees C, the rate constant for helix formation, k1, increased by a factor of 210, and the reverse rate constant, k(-1), decreased by a factor of 420 upon increasing f(G x C) from 0.14 to 0.5. The activation energies for formation of the duplexes were negative and relatively insensitive to f(G x C). The pressure-induced change in the rate constants is related to the activation volume of the reaction step. Pressure causes k1 to become larger, and the magnitude of the change in k1 with pressure increases the lower the f(G x C) value. Thus, when f(G x C) = 0.14, the activation volume for forward reaction, delta V++(1), equals -20 mL/mol, while when f(G x C) = 0.5, delta V++(1) = -6.7 mL/mol. The rate constant for strand separation, k(-1), decreases at high pressure. The activation volume for this step, delta V++(1), varies from 17 to 1.6 mL/mol when f(G x C) = 0.14 and 0.5, respectively. The delta V for helix formation calculated from the activation parameters changed from -23 mL/mol when f(G x C) = 0.14 to -5.8 mL/mol when f(G x C) = 0.5. From extrapolation, it is estimated that the molar volume change for formation of G x C base pairs in homopurine-homopyrimidine sequences is approximately 0 mL/mol. Parameters calculated from kinetics of other two duplex molecules, when f(G x C) = 0.23 and 0.32, lie between these extremes.

Base Composition↗
PubMed1997

Shear stress induction of the tissue factor gene.

Using flow channel, we report that the application of a laminar shear stress induced a transient increase of tissue factor (TF) procoagulant activity in human umbilical vein endothelial cells (HUVEC), which was accompanied by a rapid and transient induction of the TF mRNA in the HUVEC. Functional analysis of the 2.2 kb TF 5' promoter indicated that a GC-rich region containing three copies each of the EGR-1 and Sp1 sites was required for induction. Mutation of the Sp1 sites, but not the EGR-1 sites, attenuated the response of TF promoter to shear stress. Thus, Sp1 is a newly defined shear stress responsive element. Electrophoretic mobility shift assays showed there was no increase in binding of nuclear extracts from sheared cells to an Sp1 consensus site. In contrast, immunoblotting of these nuclear extracts with antibody against transcription factor Sp1 demonstrated that shear stress increased the phosphorylation of Sp1. We also showed that shear stress, like the phosphatase inhibitor okadaic acid, increased the transcriptional activity of Sp1. These findings suggest that the shear stress induction of TF gene expression is mediated through an increased Sp1 transcriptional activity with a concomitant hyperphosphorylation of Sp1.

Endothelium, Vascular↗
PubMed1997

Channel formation by a neurotoxic prion protein fragment.

Prions cause neurodegenerative disease in animals and humans. Recently it was shown that a 21-residue fragment of the prion protein (106-126) could be toxic to cultured neurons. We report here that this peptide forms ion-permeable channels in planar lipid bilayer membranes. These channels are freely permeable to common physiological ions, and their formation is significantly enhanced by "aging" and/or low pH. We suggest that channel formation is the cytotoxic mechanism of action of amyloidogenic peptides found in prion-related encephalopathies and other amyloidoses. The channels reported here are large enough and nonselective enough to mediate cell death through discharge of cellular membrane potential, changes in ionic homeostasis, and specifically, influx of calcium, perhaps triggering apoptosis.

Electric Conductivity↗
PubMed1997

Effects of indoor environmental factors on respiratory health of children in a subtropical climate.

This study was conducted to determine whether indoor environmental factors affected respiratory symptoms in 4164 primary school children in Kaohsiung rural areas of Taiwan. Information on respiratory health symptoms and characteristics of the housing was obtained using a written questionnaire, completed by the parents of children. Multiple logistic regression analysis examined the relationship between respiratory health symptoms (cough, wheezing, bronchitis, asthma, and allergic rhinitis) and housing factors. Home dampness was significantly associated with all respiratory health symptoms. Incense burning and mosquito repellant burning showed effects on the reporting of coughing symptoms. No apparent associations were found with the other indoor factors included in this study or respiratory health symptoms. We conclude that dampness in the home has a pronounced effects on respiratory health symptoms and is a new public health issue in subtropical areas.

Air Pollution, Indoor↗
PubMed1997

Ethanol down-regulates the transcription of microsomal triglyceride transfer protein gene.

Microsomal triglyceride transfer protein (MTP) plays a central role in the assembly and secretion of apoB-containing lipoproteins. In this study, we investigated the effect of ethanol on the expression of the large subunit of MTP in a human liver hepatoma cell line, the HepG2 cells. Exposure of HepG2 cells to low concentrations of ethanol reduced MTP mRNA levels in a concentration- and time-dependent manner. The level of MTP mRNA decreased significantly (P<0.05, -26% relative to pretreatment control) when the concentration of ethanol in the culture medium was 50 ppm (0.005%, v/v). Maximal suppression (-50%) was observed at 100 ppm ethanol; the MTP mRNA levels remained at 50% of control when the ethanol concentration was raised to 10,000 ppm. Furthermore, a 10-day ethanol treatment caused a significant 50% decrease in the MTP activity and apoB secretion rate in HepG2 cells. To investigate the molecular mechanisms underlying this phenomenon, we examined the effect of ethanol on the promoter activity of the MTP gene. Transient transfection analysis of human MTP promoter-driven luciferase gene expression showed that ethanol down-regulates MTP promoter activity in a manner parallel to that observed for mRNA levels. Deletion analysis suggested that the MTP promoter sequence contains a negative ethanol response element -612 to -142 bp upstream of the transcription start site. To evaluate the in vivo relevance of the effect of ethanol on MTP mRNA levels, rats were given a single oral dose of ethanol, with hepatic and intestinal MTP mRNA measured 3 h after dosing. Rats receiving 1 or 3 g/kg of ethanol exhibited substantially lower hepatic and intestinal MTP mRNA levels. Taken together, these results strongly suggest that ethanol can modulate the secretion of apoB-containing lipoproteins by down-regulating the expression of MTP large subunit, primarily through inhibiting the transcription of the MTP gene.

Animals↗
PubMed1997

Geographic variations in mortality from motor vehicle crashes in Taiwan.

Mortality from motor vehicle crashes within five urbanization categories in Taiwan between 1981 and 1990 was investigated. Sex-specific standardized mortality ratios (SMRs) were calculated within each urbanization category for motor vehicle crash deaths. Most urban areas demonstrated lower SMRs for both males and females. In contrast, most rural areas exhibited higher SMRs for both males and females. Both males and females demonstrated a significant linear relationship between decreasing urbanization and increasing SMRs for motor vehicle crash mortality. A variety of factors may underlie the inverse correlation between SMRs for motor vehicle crashes and urbanization category. These data are most useful in generating hypotheses for further studies to define specific etiological factors operating within urbanization categories.

Accidents, Traffic↗
PubMed1997

Respiratory drive and pulmonary mechanics during haemodialysis with ultrafiltration in ventilated patients.

The improvements of respiratory drive and pulmonary mechanics which follow haemodialysis with ultrafiltration in mechanically ventilated renal failure patients seem predictable but have not been studied before. In this study, 14 renal failure patients with stable haemodynamics mechanically ventilated with pressure support ventilation (PSV) were enrolled. Respiratory drive (represented as P0.1), pulmonary mechanics, breathing pattern, arterial blood gas and haemodynamics were measured according to the time schedule: pre-dialysis (Time 0), and at 60, 120, 180, 240 minutes thereafter. Following the removal of excess lung water during haemodialysis, auto-PEEP and patient's work of breathing (WOBp) decreased gradually. P0.1 lessened progressively along with the improvement in pulmonary mechanics. The changes in auto-PEEP and WOBp correlated closely to the pre- and post-dialysis decline of P0.1 (delta P0.1). There was a negative, moderately significant correlation between the amount of fluid ultrafiltrated during dialysis (delta UF) and the delta P0.1 (R = -0.54). The breathing pattern remained stable during dialysis. No hypoventilation or hypoxaemia occurred despite the development of metabolic alkalosis induced by bicarbonate dialysate. We have shown that respiratory drive decreases gradually during bicarbonate haemodialysis. The improvements of pulmonary mechanics, rather than the rapid alkalization of body fluids, responds to the decrease of P0.1 in renal failure patients ventilated with PSV.

Aged↗
PubMed1997

Bilateral diaphragmatic paralysis--a rare cause of acute respiratory failure managed with nasal mask bilevel positive airway pressure (BiPAP) ventilation.

A 68 yr old woman presented with acute respiratory failure. She was suspected of having a phrenic-diaphragmatic impairment, without evidence of an intrinsic lung disease or generalized neuromuscular disorder, after 3 weeks of prolonged mechanical ventilation. A series of studies, including fluoroscopy, phrenic nerve stimulation test and diaphragmatic electromyography, was performed before the diagnosis of bilateral diaphragmatic paralysis (BDP) was confirmed. The patient was successfully weaned from the conventional mechanical ventilator, and was placed on nasal mask bi-level positive airway pressure (BiPAP) ventilation. A high degree of clinical suspicion of bilateral diaphragmatic paralysis should always be raised in patients suffering respiratory failure without definite predisposing factors. Weaning with noninvasive nasal mask ventilation should be tried first instead of direct tracheostomy.

Acute Disease↗
PubMed1997

A multidisciplinary pulmonary rehabilitation program for patients with moderately severe chronic obstructive pulmonary disease.

A multidisciplinary pulmonary rehabilitation program was conducted for 13 outpatients (mean age 66 +/- 6.7 yr) with moderately severe chronic obstructive pulmonary disease. Changes in pulmonary function and blood gas data were not significant. Exercise capability, including 6-minute walking distance (WkD6), maximal work load (WkLmax), endurance time, and maximum heart rate, improved significantly (p < 0.05), as did subjective symptoms and quality of life. Of the observed changes, only baseline PaO2 and oxygen saturation were positively correlated with changes in maximum heart rate. The initial maximum heart rate was inversely related to both the absolute and percentage improvement. There were no significant relationships between improvement in WkD6 and age, initial arterial blood gas, or pulmonary function, but a significant relationship was found between baseline forced expired volume in the first second (FEV1) and percentage change in WkLmax. Our results indicate that patients with moderately severe chronic obstructive pulmonary disease can improve their exercise capacity, subjective symptoms, and quality of life through a pulmonary rehabilitation program. All patients can increase their endurance, regardless of their initial exercise performance. Maximum heart rate and FEV1 are predictors of exercise capability improvement.

Aged↗
PubMed1996

The activation volume of a DNA helix-coil transition.

The role of hydration in the kinetics of a DNA helix-coil equilibrium is investigated by studying the effect of hydrostatic pressure on the rate constants describing the reaction. The kinetics were measured using the thermal hysteresis between the denaturation and renaturation curves of the triplex-forming oligonucleotides: 5'd[AAA-GGAGGAGAAGAAGAAAAAA] (sequence of purine strand) and 5'd[TTTCCTCCTCTTCTTCTTTTTT] (third strand). The kinetics at atmosphere pressure for this system have been recently reported [Rougée et al. (1992) Biochemistry 31, 9269-9278]. At all pressures the data are consistent with a single-step bimolecular reaction under the conditions of our experiments (100 mM NaCl, 10 mM cacodylate, pH 6.5). The rate of formation of the triplex from the duplex + single strand is accelerated by pressure. At the midpoint of the helix-coil transition (32.5 degrees C), the activation volume for helix formation, V*1, equals -11.8 (+/- 2.4) cm3 mol-1 at atmospheric pressure. At the same temperature, the activation volume for helix dissociation, V*-1, equals +39.9 (+/- 5.0) cm3 mol-1; that is, the rate of strand separation is slowed by pressure. These findings emphasize the importance of solvent interactions in the stabilization and formation of DNA helices. It is proposed that the activation volume of the forward reaction may arise from the volume change due to charging the cytosine residues and the formation of base-stacking interactions in the third strand. The positive activation volume of strand separation may be a consequence of poor solvent packing of the DNA duplex major groove during dissociation of the third strand.

Base Sequence↗
PubMed1996

Pore formation by the cytotoxic islet amyloid peptide amylin.

Amylin is a 37-amino acid cytotoxic constituent of amyloid deposits found in the islets of Langerhans of patients with type II diabetes. Extracellular accumulation of this peptide results in damage to insulin-producing beta cell membranes and cell death. We report here that at cytotoxic concentrations, amylin forms voltage-dependent, relatively nonselective, ion-permeable channels in planar phospholipid bilayer membranes. Channel formation is dependent upon lipid membrane composition, ionic strength, and membrane potential. At 1-10 microM, cytotoxic human amylin dramatically increases the conductance of lipid bilayer membranes, while non-cytotoxic rat amylin does not. We suggest that channel formation may be the mechanism of cytotoxicity of human amylin.

Amyloid↗
PubMed1996

Protective effect of diallyl sulfone against acetaminophen-induced hepatotoxicity in mice.

Diallyl sulfone (DASO2) is a metabolite of diallyl sulfide, a compound derived from garlic. The present study investigated the effect of DASO2 as a protective agent against acetaminophen (APAP)-induced hepatotoxicity in mice. Oral administration of DASO2 protected mice against the APAP-induced hepatotoxicity in a dose- and time-dependent manner. When administered 1 hour prior to, immediately after, or 20 minutes after a toxic dose of APAP, DASO2 at a dose of 25 mg/kg completely protected mice from development of hepatotoxicity, as indicated by liver histopathology and serum lactate dehydrogenase levels. Protective effect was observed when DASO2 at a dose as low as 5 mg/kg was given to mice 1 hour prior to APAP administration. Oral administration of DASO2 to mice 1 hour prior to a toxic dose of APAP significantly inhibited the APAP-induced glutathione depletion in the liver. DASO2 treatment also decreased the levels of oxidative APAP metabolites in the plasma without affecting the concentrations of nonoxidative APAP metabolites. In liver microsomes, 0.1 mM of DASO2 caused a 60% decrease in the rate of APAP oxidation to N-acetyl-p-benzoquinone imine, which was determined as glutathione conjugate. This inhibitory effect is mainly due to its inhibition of cytochrome P450 2E1 activity; with an IC50 value equal to 0.11 mM. DASO2 also slightly inhibited the activities of P450s 3A and 1A, with IC50 values > 5 mM. Furthermore, a single oral dose of DASO2 inactivated P450 2E1- and P450 1A-dependent activities in liver microsomes. The results suggest that the protective effect of DASO2 against APAP-induced hepatotoxicity is due to its ability to block acetaminophen bioactivation mainly by the inactivation and inhibition of P450 2E1.

Acetaminophen↗
PubMed1996

Chronic intrathecal morphine treatment does not cause down-regulation of spinal adenosine A1 receptors in rats.

We have shown previously that systemic chronic morphine treatment causes down-regulation of spinal adenosine A1 receptors in rats. Recently, we have found that chronic supraspinal morphine treatment also causes this effect. In the present study, we investigated whether chronic spinal morphine treatment has the same effect of down-regulation of spinal adenosine A1 receptors. Adult male Sprague-Dawley rats were rendered tolerant to morphine either by multiple intrathecal (i.t.) injections or continuous i.t. infusion by osmotic pump administration for 2 or 4 days. Spinal A1-adenosine receptor binding activity was measured by using the selective A1 adenosine agonist [3H]cyclohexyladenosine. No significant decrease in [3H]cyclohexyladenosine binding was found in the spinal cord after 2 or 4 days of multiple i.t. injections of morphine. There was also no significant change in the amount of spinal [3H]cyclohexyladenosine bound after 4 days of continuous i.t. infusion of morphine by osmotic pump. From these and our previous results, it is concluded that only supraspinal chronic morphine treatment down regulates the spinal A1 adenosine receptor and this may play a role in the mechanism of supraspinal morphine tolerance but not spinal morphine tolerance.

Adenosine↗