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Biomedical subjects

C L Chen

Publications and source records attributed to C L Chen.

At least 109 records · Page 6Linked to original sources
PubMed2000

RAG2-/-, I kappa B-alpha-/- chimeras display a psoriasiform skin disease.

Nuclear factor-kappa B, a ubiquitous transcription factor involved in inflammatory and immune responses, is inappropriately activated in several immuno-related diseases, such as allograft rejection, or bronchial asthma. As nuclear factor-kappa B activity is regulated by inhibitor of kappa B (I kappa B), the gene encoding I kappa B-alpha was disrupted in mice to observe the in vivo effects of hyperactivation of nuclear factor-kappa B. I kappa B-alpha-/- mice have constitutive nuclear factor-kappa B activity, severe skin disease, and neonatal lethality. To determine the role of I kappa B-alpha deficient immunocytes in the pathogenesis of the skin disease in adult mice, we utilized the RAG2-deficient blastocyst complementation system to generate RAG2-/-, I kappa B-alpha-/- chimeras. These animals display a psoriasiform dermatitis characterized by hyperplastic epidermal keratinocytes and dermal infiltration of immunocytes, including lymphocytes. Skin grafts transferred from diseased chimeras to recipient nude mice produce hyperproliferative psoriasiform epidermal keratinocytes in response to stimulation. Furthermore, adoptive transfer of lymph node cells from diseased chimeras to RAG2-/- recipient mice recapitulates the disease. Taken together, these characterizations provide evidence to suggest that constitutive activation of nuclear factor-kappa B, due to deficiency in I kappa B-alpha, can invoke severe psoriasiform dermatitis in adult mice. J Invest Dermatol 115:1124-1133 2000

Animals↗
PubMed2000

Correlation of polyelectromyographic patterns and clinical upper motor neuron syndrome in hemiplegic stroke patients.

OBJECTIVE: To investigate the correlation between movement patterns, measured by polyelectromyography (PEMG), and clinical upper motor neuron (UMN) syndrome in stroke patients. DESIGN: PEMG patterns, recorded from pairs of flexor-extensor muscles during voluntary maneuvers, and motor outcomes were assessed approximately 1 month after stroke (early stage). Motor outcomes were reassessed 6 months later (late stage). PARTICIPANTS: Thirty-nine hemiplegic stroke patients and 18 healthy control subjects. MAIN OUTCOME MEASURES: Passive stretch reflexes (PSRs), Brunnstrom's stages, and walking ability. RESULTS: Six PEMG patterns, varying from complete reciprocal to complete synchrony, were identified. Higher PEMG pattern scores were associated with better Brunnstrom's stages (r > .80), walking ability (r > .39), and some PSRs (r < -.37). PEMG patterns could separate patterns 1 and 2 from patterns 3 and 4 for patients with early Brunnstrom's stages 1 and 2. Patterns 1 and 2 (reduced agonist electromyographic activities) indicated weakness and resulted in the worst motor outcomes. Patterns 3 and 4 (cocontraction and coactivation) indicated spasticity and associated synergistic movements. Patients with patterns of 5 and 6 (reciprocal electromyographic activities) had more selective motor control. CONCLUSIONS: PEMG patterns correlate with clinical UMN syndromes and may allow treatment strategy planning on the basis of underlying motor control, as well as the prediction of final motor outcomes soon after stroke, even in patients who cannot move their legs initially.

Aged↗
PubMed2000

Brain lesion size and location: effects on motor recovery and functional outcome in stroke patients.

OBJECTIVE: To investigate effects of brain lesion profiles that combined sizes and locations on motor recovery and functional outcome after stroke in hemiplegic patients. DESIGN: Delimiting sizes (a threshold lesion size) of 5 primary locations were identified to establish brain lesion profiles based on magnetic resonance imaging findings 1 month after stroke. Motor and functional outcome were correlated with brain lesion profiles and other brain lesion factors to identify the most dominant factor. SETTING: Medical center, rehabilitation department. PARTICIPANTS: Fifty-five hemiplegic patients. MAIN OUTCOME MEASURES: Brunnström's stages and Functional Independence Measure (FIM) scores were assessed 1 and 6 months after stroke. RESULTS: With delimiting sizes for the cortical, corona radiata, internal capsule, putaminal, and thalamic regions set at 75, 4, .75, 22, and 12cm3, respectively, brain lesion profiles play a dominant role in determining final Brunnström's stages (Spearman's rho = .861, p < .01) and FIM score (Spearman's rho = .571, p < .01). Brunnström's and FIM scores had no or only weak negative relationship with either absolute or relative lesion size. CONCLUSIONS: These findings may suggest that motor and functional outcomes after stroke correlate with brain lesion profiles (a combination of delimiting sizes and primary locations) more than with absolute or relative lesion sizes only. Delimiting sizes in determining final outcomes varied markedly according to the primary lesion locations.

Aged↗
PubMed2000

Major hepatic resection may suppress the growth of tumours remaining in the residual liver.

Little is known as to how hepatectomy is associated with the growth of hepatic tumours, which may reside in the remaining liver after curative resection for hepatocellular carcinoma. Using an intra-hepatic tumour implantation model in rats, the effects of hepatectomy on tumour growth in the remaining liver were investigated. On post-operative day 7, the tumour weight in the remaining liver following 30% hepatectomy was 0.321+/-0.058 g (mean +/- SD) which was significantly greater than that (0.245+/-0.040 g) in sham operations (P<0.05). However, the tumour weight (0.156+/-0.067 g) in the remaining liver following 60% hepatectomy was significantly lower than that in sham animals (P< 0.005). The number of TdT-mediated dUTP nick-end labelling (TUNEL) positive tumour cells was significantly increased in 60% hepatectomy as compared with the sham and 30% hepatectomy group. The mRNA expression of TGF-beta1, TNF-alpha and Fas in the tumour portion of 60% hepatectomy, was higher than that in 30% hepatectomy group. Plasma levels of TGF-beta1 were inversely correlated with intra-hepatic tumour weights. These results suggest that major hepatic resection may lead to an increased induction of apoptosis for the remaining hepatic tumour.

Animals↗
PubMed2000

Elevated expression of thyroid hormone receptor alpha 2 (c-erb A- alpha 2) in nasopharyngeal carcinoma.

Differential display was used to identify genes differentially expressed between cultured normal nasal epithelial cells and nasopharyngeal carcinoma (NPC) cell lines. A 130 bp cDNA fragment showing homology with thyroid hormone receptor alpha2 (TR-alpha2 or c-erb A-alpha2) was identified in NPC cell lines. Northern blot analysis using the 130 bp cDNA fragment and a TR-alpha2 specific cDNA containing part of the coding region as probes, we were able to detect a 2.7 kb transcript corresponding to that of TR-alpha2 in NPC cell lines but not in normal nasal epithelial cells. RNA in situ hybridization was used to detect TR-alpha2 expression in clinical biopsies obtained from NPC patients and non-tumour controls. TR-alpha2 mRNA was detected in 1 out of 24 (4.2%) normal nasopharynx epithelium biopsies, in 5 out of 27 (18.5%) primary and 15 out of 24 (62.5%) recurrent tumours. The positive rate of TR-alpha2 expression in recurrent NPC biopsies was significantly higher than that in normal nasopharynx epithelium (P<0.00001). The relevance of the elevated expression of TR-alpha2 in the pathogenesis process of NPC was discussed.

Adult↗
PubMed2000

Preliminary acute and subchronic toxicity studies of GLG-V-13, a novel class III antiarrhythmic agent, in mice.

The acute and subchronic toxic effects of GLG-V-13 (3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo[3.3.1]nona ne dihydroperchlorate, CAS 155029-33-7), a novel class III with some class Ib antiarrhythmic activity, were investigated in mice. The estimated LD50 for GLG-V-13 given orally were 419 mg/kg for male mice and 383 mg/kg for female mice, respectively. The acute toxic signs appeared to be of the central nervous system in origin. Four groups of mice (15 per sex, group and dose) were fed daily with diets containing GLG-V-13 for 90 consecutive days. The equivalent daily doses were 0, 22, 50 and 121 mg/kg/day and 0, 27, 60 and 136 mg/kg/day for male and female mice, respectively. All of the mice survived. Food consumption was decreased. However, mean body weight and body weight gain were not significantly changed. Gross pathological changes, especially in the lungs and liver, were found in the middle and high dose groups. Consistent increased mean corpuscular hemoglobin concentration and decreased mean corpuscular hemoglobin were observed in all dose groups. Hepatocellular necrosis was found in both male and female mice treated with the drug and was dose-dependent. Marked vacuolation of the X zone in the adrenal gland with mild to moderate deposition of ceroid pigments (brown degeneration) was observed in female mice. Lesions in the kidneys and adrenal glands may be a possible reason for changes in serum sodium and potassium ions concentrations leading to an increase in water intake. A significant reduction in cholesterol in the high dose group may be a favorable pharmacological effect of GLG-V-13. The data from the 90-day subchronic toxicity studies indicate that GLG-V-13 appears to have limited systemic toxicity potential.

Animals↗
PubMed2000

Treatment of atherosclerosis in apolipoprotein E-deficient mice with 4-(3-Bromobenzoyl)-6,7-dimethoxyquinazoline (WHI-P164), a potent inhibitor of triglyceride synthesis.

We identified a novel organic compound, 4-(3'-bromobenzoyl)-6,7-dimethoxyquinazoline (compound WHI-P164), as a potent inhibitor of triglyceride (TG) synthesis. In an in vitro model of lipid synthesis, WHI-P164 (but not any one of the three structurally similar control dimethoxyquinazoline compounds) inhibited the accumulation of TG-rich intracellular lipid droplets in Caco-2 human intestinal cells in a concentration-dependent fashion. WHI-P164 caused no acute toxicity associated with morbidity or mortality in mice when administered at dose levels ranging from 0.5 to 80 mg/kg. In pharmacokinetic studies in mice, WHI-P164 was rapidly eliminated from plasma with a terminal elimination half-life of 26.1 +/- 1.3 min after intraperitoneal administration and 33.3 +/- 11.3 min after intravenous administration. Treatment with 40 mg/kg WHI-P164 (but not one of three structurally similar control dimethoxyquinazoline compounds) administered intraperitoneally once daily for 7 consecutive treatment days blocked the in vivo hepatic TG synthesis in both apoE-deficient and wild-type C57B1/6 mice. In apoE-deficient mice maintained on a high-fat/high-cholesterol Western diet, WHI-P164 substantially reduced the lipid accumulation in the liver after 7 days of treatment and the lipid accumulation in the aorta after 1 month of treatment. Our results in apoE-deficient mice show that lipid accumulation in hepatocytes and foam cells are related events, and inhibiting TG synthesis with WHI-P164 offers an effective means to treat atherosclerosis.

Animals↗
PubMed2000

Multiorgan nuclear factor kappa B activation in a transgenic mouse model of systemic inflammation.

We utilized a line of transgenic mice expressing Photinus luciferase complementary DNA (cDNA) under the control of a nuclear factor kappa B (NF-kappaB)-dependent promoter (from the 5' human immunodeficiency virus-1 [HIV-1] long terminal repeat) to examine the role of NF-kappaB activation in the pathogenesis of systemic inflammation induced by bacterial endotoxin (lipopolysaccharide [LPS]). After intraperitoneal injection of E. coli LPS, these mice displayed a time- and dose-dependent, organ-specific pattern of luciferase expression, showing that NF-kappaB-dependent gene transcription is transiently activated in multiple organs by systemic LPS administration. Luciferase expression in liver could be specifically blocked by intravenous administration of replication-deficient adenoviral vectors expressing a dominant inhibitor of NF-kappaB (IkappaB-alphaDN), confirming that luciferase gene expression is a surrogate marker for NF-kappaB activation in this line of mice. After treatment with intraperitoneal LPS, the mice were found to have increased lung tissue messenger RNA (mRNA) expression of a variety of cytokines that are thought to be NF-kappaB-dependent, as well as elevated serum concentrations of presumed NF-kappaB-dependent cytokines. In lung tissue homogenates, a close correlation was identified between luciferase activity and KC levels. These studies show that systemic treatment with LPS orchestrates a multiorgan NF-kappaB-dependent response that likely regulates the pathobiology of systemic inflammation.

Animals↗
PubMed2000

GATA-1 and GATA-4 transactivate inhibin/activin beta-B-subunit gene transcription in testicular cells.

We have recently demonstrated that a testicular GATA-binding protein, GATA-1, up-regulates the transcription of inhibin alpha-subunit gene through interaction with GATA motifs in the promoter region in MA-10, a mouse Leydig tumor cell line. In this study, we showed that both GATA-1 and GATA-4 also transactivated the transcription from the promoter for the 4.8-kb inhibin/activin beta-B-subunit gene transcripts, beta-B(4.8)-subunit promoter, in two testicular cell lines, MA-10 and MSC-1, which is a mouse Sertoli cell line. The abilities of GATA-1 and GATA-4 interacting with GATA and/or GATA-like sequences to transactivate the beta-B(4.8)-subunit promoter were next examined by mutation analysis. Mutations of GATA or GATA-like sequences caused no apparent effect or only a small decrease in the basal transcriptional activity of this promoter. However, mutation of the GATA motif at -65 markedly decreased 60-70% of the effect of GATA-1 on the transactivation of beta-B(4.8)-subunit promoter in both MA-10 and MSC-1 cells. In addition, mutation of the GATA motif in MSC-1 cells also reduced 40-50% of the effect of GATA-4 to transactivate this promoter. Interestingly, mutation of GATT at -42 caused a 70-90% increase in the transactivation of beta-B(4.8)-subunit promoter by GATA-1 or GATA-4. No significant change in the promoter activity was observed when GATT at -177 or GATC at -201 was mutated. Electrophoretic mobility shift assay confirmed the above observations that these GATA-binding proteins interacted with the GATA motif at -65 and GATT at -42, but not with GATC at -201 or GATT at -177. Serial deletion from the 5'-end of the basal promoter, from -226 to -90, markedly decreased the basal transcription, but increased the effect of GATA-1 on transactivation of the beta-B(4.8)-subunit promoter. In summary, our observations suggest that the two GATA-binding proteins transactivate the beta-B(4.8)-subunit promoter in testicular cells via complicated mechanisms. Both GATA-1 and GATA-4 factors act through the GATA motif at -65 and GATT at -42 to positively and negatively regulate the transcription from this promoter, respectively. Furthermore, GATA-1 may also interact directly or indirectly with DNA sequences at -180 to -90 to regulate the beta-B(4.8)-subunit promoter.

Activins↗
PubMed2000

Loss of imprinting of the IGF-II and H19 genes in epithelial ovarian cancer.

To establish a possible role of genomic imprinting in the carcinogenesis of epithelial ovarian cancer, we determined the imprinting status of both IGF-II and H19 genes in 43 ovarian cancers, 7 low malignant potential ovarian tumors, and their matched normal tissues. In ovarian cancer, loss of heterozygosity (LOH) of IGF-II, H19 RsaI, and H19 AluI was found in 4 of 24 (16.7%), 3 of 20 (15%), and 1 of 16 (6.3%) samples, respectively. All patients with tumor specimens exhibiting LOH are of advanced clinical stages. Loss of imprinting (LOI) was found in 5 of 20 (25%) for IGF-II and in 4 of 17 (23.5%) and 1 of 15 (6.7%) for the RsaI and AluI sites of H19 gene with no LOH. However, no LOH was found in low malignant potential tumors, and only one of them showed LOI in H19 AluI site. Overexpression of IGF-II was demonstrated in all five LOI samples with normal expression of H19. Three of the five tumor specimens exhibiting LOI were transcribed from P1 promoter, whereas the remaining two were from the P3 promoter. These results suggested that LOH of both IGF-II and H19 genes was associated with advanced ovarian cancer. LOI of IGF-II and H19 genes may be involved in the development of ovarian cancer. Transcription of IGF-II from the P1 promoter may account for the biallelic expression of the IGF-II gene.

Female↗
PubMed2000

[Glucose isomerase gene knock-out by denatured double-stranded DNA].

After Genetic background analysis of Streptomyces diastaticus No. 7 strain M1033, the modified conditions of M1033 protoplasts and transformation were established. Replacement plasmid for homologous recombination was also constructed by inserting tsr gene into glucose isomerase gene. The homologous recombination of GI gene in M1033 chromosomes was achieved by using denatured linearized DNA fragments and glucose isomerase deficient strain M1033LJ was obtained. It is basic for introducing mutation into M1033 chromosome and realizing site-directed molecular reformation.

Aldose-Ketose Isomerases↗
PubMed2000

P73 gene expression in ovarian cancer tissues and cell lines.

Thep73 gene, a homology of p53, is a new candidate of imprinting and tumor suppressor gene. To investigate the role of p73 in ovarian cancer, we studied the allelic expression in 56 cases of ovarian cancer using StyI polymorphism analysis. We also examined p73 expression by semi-quantitative reverse transcription-PCR as well as by Western blot analysis and DNA methylation study of the CpG island in exon 1 in ovarian cancer tissues and cell lines. Loss of heterozygosity was found in 8.3% (2 of 24) of the cases. Biallelic expression was demonstrated in 91.7% (22 of 24) of the tumor samples, in 70.8% (17 of 24) of the normal samples, and in 1 ovarian cancer cell line. Imbalanced expression and monoallelic expression were found in three and two pairs of matched samples, respectively. Overexpression of p73 was found in advanced ovarian cancer rather than in early-stage disease or in borderline ovarian tumor. No significant difference was found in the p53 expression. Three cell lines with absent p73 protein expression and one tumor sample with monoallelic expression were methylated in the CpG island. Demethylation in SKOV3 cell line using 5-azacytidine can reactivate the expression of this gene in both the mRNA and the protein level. Our results indicated that p73 was not imprinted in most of the ovarian cancer and normal tissues, but it could be involved in the advanced ovarian cancer through overexpression. DNA methylation may contribute to the lack of p73 expression.

Adenocarcinoma, Clear Cell↗
PubMed2000

Treatment of allergic asthma by targeting janus kinase 3-dependent leukotriene synthesis in mast cells with 4-(3', 5'-dibromo-4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline (WHI-P97).

4-(3',5'-Dibromo-4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline (WHI-P97) is a rationally designed potent inhibitor of Janus kinase (JAK)-3. Treatment of mast cells with WHI-P97 inhibited the translocation of 5-lipoxygenase (5-LO) from the nucleoplasm to the nuclear membrane and consequently 5-LO-dependent leukotriene (LT) synthesis after IgE receptor/FcepsilonRI crosslinking by >90% at low micromolar concentrations. WHI-P97 did not directly inhibit the enzymatic activity of 5-LO, but prevented its translocation to the nuclear membrane without affecting the requisite calcium signal. WHI-P97 was very well tolerated in mice, with no signs of toxicity at dose levels ranging from 5 microg/kg to 50 mg/kg, and LD(10) was not reached at a 50 mg/kg dose level when administered as a single i. p. or i.v. bolus dose. Therapeutic WHI-P97 concentrations, which inhibit mast cell leukotriene synthesis in vitro, could easily be achieved in vivo after the i.v. or i.p. administration of a single nontoxic 40 mg/kg bolus dose of WHI-P97. Notably, WHI-P97 showed promising biological activity in a mouse model of allergic asthma at nontoxic dose levels. Treatment of ovalbumin-sensitized mice with WHI-P97 prevented the development of airway hyper-responsiveness to methacholine in a dose-dependent fashion. Furthermore, WHI-P97 inhibited the eosinophil recruitment to the airway lumen after the ovalbumin challenge in a dose-dependent fashion. Further development of WHI-P97 may therefore provide the basis for new and effective treatment as well as prevention programs for allergic asthma in clinical settings.

Animals↗
PubMed2000

Adrenal ganglioneuroma: report of five cases.

Adrenal ganglioneuromas are rare tumors originating from the neural crest tissue of the sympathetic nervous system. The clinical presentation of most patients is asymptomatic, and most of these tumors are hormone silent. Usually the tumor is detected incidentally by abdominal imaging studies for unrelated reasons. Herein, we review our cases of adrenal ganglioneuroma over the past 20 years. All patients diagnosed with primary adrenal ganglioneuroma between 1979 and 1999 were reviewed. There were 5 cases of pathologically confirmed adrenal ganglioneuroma. All patients underwent surgical excision of the adrenal tumors. The mean age of the 5 patients (3 women and 2 men) was 27 years (range, 11 to 45 years). The average diameter of the tumor was 8.2 cm (range, 6 to 10 cm). The mean follow-up period was 33.6 months (range, 3 to 92 months). One case involved mesenteric lymph nodes. This patient had persistent hypertension following the operation, but no evidence of tumor recurrence was noted over the 7-year follow-up period. The prognosis was excellent after surgical excision in our series. Awareness of this rare entity may add to the differential diagnoses of adrenal masses preoperatively.

Adolescent↗
PubMed2000

Review of pre-eclampsia in Taiwan: a multi-institutional study.

BACKGROUND: Because the reported frequency of pre-eclampsia in Taiwan varies significantly, the aims of this study were to measure the current incidence of pre-eclampsia and its correlated morbidity and mortality for both mothers and fetuses in Taiwan. METHODS: We retrospectively studied all reported cases of pre-eclampsia and eclampsia from January 1, 1993 to December 31, 1997 in the 14 tertiary medical centers and regional hospitals in Taiwan. Recruiting criteria were pregnancy-induced hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg) with proteinuria (> or = 300 mg of urinary protein per 24 hours) and independent part edema. RESULTS: There were 4,193 patients with pre-eclampsia and eclampsia for a frequency of 2.03% of 206,551 deliveries during the study period. Of these, 58.9% of patients were classified as having mild pre-eclampsia while 38.4% had severe pre-eclampsia. Advanced maternal age (> 35 years) (odds ratio [OR] = 4.56; 95% confidence interval [CI] = 4.23-4.90; p < 0.001), primiparity (OR = 1.71; 95% CI = 1.61-1.82; p = 0.02) and twin pregnancy (OR = 1.92; 95% CI = 1.64-2.25; p = 0.01) were significant risk factors for developing pre-eclampsia. However, multivariate analysis showed that only advanced maternal age was a significant risk factor for pre-eclampsia (OR = 3.21; 95% CI = 2.95-3.50; p < 0.001). In contrast to mild pre-eclampsia, severe pre-eclampsia resulted in significantly worse outcomes for both mothers and fetuses. Complications in patients with severe pre-eclampsia included placental abruption, acute renal failure, pulmonary edema, postpartum hemorrhage, pleural effusion, preterm labor, intrauterine growth retardation, stillbirth, neonatal mortality and low birth weight infants, all of which occurred significantly more frequently than in patients with mild pre-eclampsia (p < 0.001). CONCLUSIONS: Pre-eclampsia remains a big challenge in modern obstetrics in Taiwan. Early diagnosis and management of patients with pre-eclampsia to prevent progression would significantly improve outcomes for mothers and fetuses.

Adult↗
PubMed1999

Activation of rat locus coeruleus neuron GABA(A) receptors by propofol and its potentiation by pentobarbital or alphaxalone.

The action of propofol on the rat locus coeruleus was examined using intracellular recording from in vitro brain slice preparations. Concentrations of propofol between 3 and 300 microM were tested. At 100 microM, propofol completely inhibited the firing of all neurons tested (n=34); this was associated with a 5.7-mV hyperpolarization (range 0-16 mV, n=33) and a 35.6% reduction in input resistance (range 7.3-66.1%, n=33). The propofol-induced responses were not affected by 2-hydroxysaclofen (50 microM) or BaCl(2) (300 microM), but were completely blocked by bicuculline methiodide (100 microM) or picrotoxin (100 microM), indicating that propofol acts on GABA(A) receptors. As assessed by inhibition of the spontaneous firing rate, propofol was 5.6-fold more potent than GABA (gamma-aminobutyric acid). Potentiation of the propofol effect by other general anesthetics or other drugs was also investigated. When pentobarbital (100 microM) was tested alone on locus coeruleus cells, no change in membrane potential or input resistance was seen and there was only a 20.3+/-7.2% (n=8) inhibition of firing rate; however, in combination with 30 microM propofol, it caused a 6.1-fold greater increase in membrane hyperpolarization and a 9.7-fold greater reduction in input resistance than 30 microM propofol alone. A relatively low concentration of alphaxalone (10 microM), when tested alone, had little effect on the membrane potential or input resistance and only produced a 46.0+/-8.9% (n=8) inhibition of firing rate; however, in combination with 30 microM propofol, it caused a 9.3-fold greater hyperpolarization and an 8.6-fold greater reduction in input resistance compared with 30 microM propofol alone. In contrast, diazepam caused no potentiation of either propofol- or GABA-induced responses. Our data also indicate that locus coeruleus neuron GABA(A) receptors possess distinctive pharmacologic characteristics, such as blocking of the propofol effects by zinc and insensitivity to diazepam and the direct action of pentobarbital. On the basis of these pharmacologic properties, we suggest that locus coeruleus neuron GABA(A) receptors do not contain the gamma subunit.

Anesthetics↗
PubMed1999

Age, gender, and local geographic variations of viral etiology of hepatocellular carcinoma in a hyperendemic area for hepatitis B virus infection.

BACKGROUND: There are etiologic variations of hepatocellular carcinoma (HCC) in different geographic areas. Taiwan is a hyperendemic area for hepatitis B virus (HBV) infection. Hepatitis C virus (HCV) infection also plays an important role in HCC development in Taiwan. Identification of local HCV-endemic areas is important to keep HCV from spreading. This study investigated the etiologic variations of HCC in different geographic areas of Taiwan. METHODS: The authors evaluated the hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV) status of 284 patients (232 male, 52 female) with HCC. They also evaluated the gender ratio and mean age of these patients. RESULTS: The mean age of HBsAg positive patients was significantly lower than the mean age of HBsAg negative patients (52.6 +/- 12.3 vs. 61.3 +/- 11.2 years) (P < 0.05). The male-to-female ratio was 4.5:1 for all HCC patients, 7:1 for HBsAg positive HCC patients, and 2.8:1 for anti-HCV positive HCC patients. In Chaiyi County in southern Taiwan, the prevalence of anti-HCV in male HCC patients was 52%, significantly greater than that of Taiwan as a whole (27.6%) (P = 0.07). However, the prevalence of anti-HCV in male HCC patients in Taipei County in northern Taiwan was 8.7%, significantly less than that of Taiwan as a whole (P = 0.043). Of a total of 65 Chiayi-based HCC patients, 55.4% were anti-HCV positive and 46.2% were HBsAg positive. In the Chiayi area, results of multiple logistic regression showed that the HCC patients who were age 60 years or older or who were living in the city area both had highly HCV-related disease. CONCLUSIONS: The mean age of patients with HBV-related HCC was significantly lower than that of patients with non-HBV-related HCC. The male-to-female ratio for patients with HBV-related HCC was significantly higher than that of patients with HCV-related HCC. The authors identified an area of Taiwan in which HCV-related HCC was prevalent.

Age Factors↗