Search PubMed⌕ Search

Biomedical subjects

T J Chen

Publications and source records attributed to T J Chen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Lymphocyte beta2-adrenergic receptors and plasma catecholamine levels in lead-exposed workers.

The effect of lead exposure on beta2-adrenoceptor density and catecholamine response was studied in 26 male workers and 1 female worker, exposed to lead on average for 6 years. The systolic blood pressure in lead workers (101-160 mmHg, 124.4 +/- 14.7 mmHg) was found to be significantly higher than in controls (97-134 mmHg, 115.4 +/- 10.4 mmHg, p < 0.01) as was plasma norepinephrine (0.51 +/- 0.1 microg/liter vs 0.24 +/- 0.05 microg/liter, p < 0.01). The density of lymphocyte beta2-adrenergic receptors (Bmax) in lead-exposed workers was 86% lower than that in controls (0.15 +/- 0.08 vs 1.08 +/- 0.29 fmol/0.1 x 10(6) cells; p < 0.01). The dissociation constants (Kd) of [125I]iodocyanopindolol were 93.6 +/- 42.6 and 87.9 +/- 42.7 pM in lead-exposed workers and controls, respectively. Multiple linear regression analysis showed that elevation of systolic pressure was closely related to (a) blood lead levels, (b) decreased beta2-adrenergic receptor density, and (c) increased plasma catecholamine levels in lead-exposed workers. Linear regression analysis revealed that both plasma norepinephrine levels and beta2-adrenoceptor density (Bmax) were highly correlated with both systolic blood pressures and blood lead levels in lead-exposed workers, and a highly significant negative correlation was found to exist between Bmax and plasma norepinephrine levels (r = -0.82, p < 0.001). These data therefore demonstrate that there is a close relationship between elevated plasma catecholamine levels, decreased beta2-adrenergic receptors, and elevated blood pressure in lead-exposed workers.

Adult↗
PubMed1996

Increased prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorder: a preliminary report.

In order to investigate the prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with and without comorbid substance use disorder, a total of 40 patients, from an outpatient neuropsychiatric clinic in Princeton, New Jersey, were genotyped for presence or absence of the Taq I DRD2 A1 allele. The primary inclusion criterion for 40 obese subjects was a body mass index (BMI) equal to or over 25 (uncharacterized); 11 obese subjects had severe substance use disorder; 20 controls had a BMI below 25; and, 33 substance use disorder (less severe) patients had a BMI below 25. The data were statistically compared with three different sets of controls divided into three separate groups (Group I, n = 20; Group II, n = 286; Group III, n = 714). They differed according to screening criteria (drug, alcohol, nicotine abuse/dependence, BMI below 25 and other related behaviours including parental history of alcoholism or drug abuse and DSM IV, Axis I and Axis II diagnoses). Groups II and III were population controls derived from the literature. The prevalence of the Taq I A1D2 dopamine receptor (DRD2) alleles was determined in 40 Caucasian obese females and males. In this sample with a mean BMI of 32.35 +/- 1.02, the A1 allele of the DRD2 gene was present in 52.5% of these obese subjects. Furthermore, we found that in the 23 obese subjects possessing comorbid substance use disorder, the prevalence of the DRD2 A1 allele significantly increased compared to the 17 obese subjects without comorbid substance use disorder. The DRD2 A1 allele was present in 73.9% of the obese subjects with comorbid substance use disorder compared to 23.5% in obese subjects without comorbid substance use disorder. Moreover, when we assessed severity of substance usage (alcoholism, cocaine dependence, etc.) increasing severity of drug use increased the prevalence of the Taq I DRD2 A1 allele; where 66.67% (8/12) of less severe probands possessed the A1 allele compared to 82% (9/11) of the most severe cases. Linear trend analyses showed that increasing use of drugs was positively and significantly associated with A1 allelic classification (p < 0.00001). These preliminary data suggest that the presence of the DRD2 A1 allele confirms increased risk not only for obesity, but also for other related addictive behaviours (previously referred to as the Reward Deficiency Syndrome) and that a BMI over 25 by itself (without characterization of macroselection or comorbid substance use disorders) is not a sufficient criterion for association with the DRD2 A1 allele.

Adult↗
PubMed1996

Impact of increased neonatal survival on postneonatal mortality in the United States.

Neonatal intensive care has increased neonatal survival, but has also led to postponement of some of the neonatal deaths to the postneonatal period, particularly in very low birthweight (< 1.5 kg) infants. Our report assesses the impact of the increased neonatal survival and the accompanying delayed deaths on the crude postneonatal mortality rate of the US, using the national livebirth cohort data of 1960, 1980, and 1986. With increased neonatal survival, very low birthweight infants comprised 0.68% of all neonatal survivors in 1986, compared with only 0.31% in 1960. However, postneonatal mortality was increased in infants with birthweights < 1.0 kg from 69 per 1000 neonatal survivors in 1960 to 116 per 1000 in 1986. All other birthweight groups (> 1.0 kg) showed significant reductions in their postneonatal mortality, although the 1.0-1.5 kg group showed the least improvement. Thus, in 1986, 12.1% of all postneonatal deaths were from the very low birthweight neonatal survivors, as compared with 2.7% in 1960. If there had been no improvement in neonatal survival of very low birthweight infants since 1960, the crude postneonatal mortality rate of the US would have been 5.5% and 7.9% less than the actual rates of 3.65 and 3.45 per 1000 neonatal survivors in 1980 and 1986, respectively. However, the impact of these delayed deaths in very low birthweight infants was far less than the increase in their neonatal survival: an additional 416 per 1000 very low birthweight infants survived to 1 year of age in 1986 as compared with 1960. Delayed deaths in the 1.5-2.5 kg birthweight group had a very small effect on postneonatal mortality and there was no such effect of delayed deaths in the > 2.5 kg birthweight group.

Age Distribution↗
PubMed1996

The D2 dopamine receptor gene as a determinant of reward deficiency syndrome.

The dopaminergic system, and in particular the dopamine D2 receptor, has been profoundly implicated in reward mechanisms in the brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance seeking behaviour (alcohol, drug, tobacco, and food) and other related behaviours (pathological gambling, Tourette's syndrome, and attention deficit hyperactivity disorder). We propose that variants of the D2 dopamine receptor gene are important common genetic determinants of the 'reward deficiency syndrome'.

Compulsive Behavior↗
PubMed1996

Determination of choline dehydrogenase activity along the rat nephron.

A radioenzymatic microassay was developed to quantitate choline dehydrogenase activity in single microdissected nephron segments. This enzyme is the rate limiting step in the biosynthesis of betaine, which serves as an intracellular osmoregulatory organic solute in mammalian kidney. The enzyme localized in renal mitochondrial inner membrane forms betaine aldehyde, which in the assay is converted to betaine by oxidative treatment. A histochemical procedure based on the formazan detection of tetranitroblue tetrazolium chloride was applied in parallel. The results show that activities in proximal convoluted and straight tubules are more than 5 times higher (21 to 25 pmol h-1 mm tubule-1) compared to distal nephron segments with no significant differences along the proximal tubule. Along the osmotic gradient from the outer medullary towards the papillary structures enzyme activities increased in ascending limbs of Henle's loop and collecting tubules. Collecting ducts showed two times higher activities than ascending loop segments when corrected for tubular cell volumes. The quantitative data were confirmed by the histochemical procedure. The results allow for the conclusion that betaine synthesis is sufficient to build up renal betaine, but cannot explain the distribution pattern of betaine along the corticopapillary axis. Additional mechanisms like intrarenal and tubular transport have to be postulated.

Alcohol Oxidoreductases↗
PubMed1995

Outcome of very low birth weight infants in industrialized countries: 1947-1987.

Neonatal intensive care has led to a progressive improvement in the survival of very low birth weight (VLBW, < 1,500 g) infants. However, it has not been established whether there has been a simultaneous increase or decrease in the prevalence of handicapping conditions in this group of children. To explore this question, a meta-analysis was performed using outcome data of 32 developmental studies of VLBW infants born in industrialized countries between 1947 and 1987. The authors' results show that the proportion of VLBW infants who survived and had an intact outcome progressively increased between 1947 and 1987--from 147 per 1,000 live births in the period 1947-1965 to 498 per 1,000 in the period 1980-1987 (p < 0.01). The prevalence of major handicapping conditions for the subset of VLBW infants who weighed < 1,000 g at birth increased, resulting from the increasing survival rates. However, the prevalence of major handicapping conditions among all children with VLBW decreased from 147 per 1,000 live births in 1947-1965 to 45 per 1,000 in 1980-1987 (p = 0.02). The authors' meta-analysis suggests that improved survival of VLBW infants has not been accompanied by an increase, but more likely a decrease, in the prevalence of handicapping conditions in this birth weight group.

Cohort Studies↗
PubMed1995

Effects of fetal brain grafting on adult behavioral masculinization and defeminization in neonatally androgenized female rats.

Treatment of neonatal female rats with androgen results not only in decreased female sexual behavior but also in enhanced male sexual behavior examined in adulthood. The effects of grafting fetal preoptic area (POA) neurons into the POA, and fetal hypothalamic (HPT) neurons into the ventromedial hypothalamus (VMH), were tested in neonatally androgen-sterilized rats (ASR). The rats were injected subcutaneously with 80 micrograms testosterone propionate within the 24 hours after birth to see if sexual behavior could be normalized by fetal brain grafts. In repeated tests on ASR grafted with fetal HPT into the VMH, the lordotic response was seen to increase to the level seen in non-ASR controls, while the increase in mounting behavior in ASR was suppressed following grafting of fetal POA or cerebral cortex into the POA. These results suggest that there are dysfunctions of POA and VMH in ASR, and that the dysfunctions revealed by sexual behavior can be overcome by fetal POA or HPT grafting.

Androgens↗
PubMed1995

Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour.

Drug and alcohol seeking behaviour has become a great global problem affecting millions of inhabitants with a cost to society in the billions. Dopaminergic reward pathways have frequently been implicated in the etiology of addictive behaviour. While other neurotransmitters have also been implicated, to date the only molecular genetic defect which has been found to associate with alcoholism, drug dependency, obesity, smoking, pathological gambling, attention-deficit-hyperactivity disorder (ADHD), Tourette syndrome, as well as other related compulsive behaviours, are the variants of the dopamine D2 receptor gene (DRD2). In this review of the available data on the subject, we report a number of independent meta-analyses that confirm an association of DRD2 polymorphisms and impulsive-additive-compulsive behaviour (IACB), which we have termed "Reward Deficiency Syndrome". While we agree that Meta-analyses of all exant studies support an association of variants of DRD2 and IACB, correct negative findings with alcoholism may be due to differences in assessing controls and inclusion/exclusion criteria for selection of diseased probands.

Behavior, Addictive↗
PubMed1995

[Locomotion of dystrophin-deficient mice].

The purpose of our study was to make a comparison of the motor function between murine dystrophy mice (MDX mice) and C57BL/10ScSn control mice. The locomotor activities of mice were measured by an animal three-dimension optical monitor. Measurements were performed at ages of 21, 45 and 60 days. Animals were tested in a dark and peaceful environment under room temperature (25 degrees C-27 degrees C) at night for an hour. Results showed that the most important differences were in data on vertical activities. Among 15 variables of locomotor activity detected by the optical activity monitor, the MDX mice and control mice at age 21 days showed significant differences in 12 variables. However, the MDX mice and control mice at age 45 days revealed significant differences in only 7 variables. The MDX mice and control mice at age 60 days had significant differences for only one variable. The results may be explained by the fact that dystrophin-deficient mice undergo more severe dystrophic degeneration at an early age (5 weeks) and new regeneration of their muscle fibres is prevalent. Moreover, a functional recovery occurred in MDX skeletal muscle which was probably due to the regeneration of dystrophic muscle.

Age Factors↗
PubMed1995

[Study of myoblast culture and myoblast transfer therapy in dystrophic mice].

In this report, we study the suitable conditions for myoblast cultures through analysis of myoblast growth and differentiation, and then try to develop a mouse model for myoblast transfer therapy (MTT). Recently, some research has indicated that Muscular Dystrophy Murine Mice (MDX) have an X-linked recessive dystrophin deficiency which is caused by dystrophin gene point mutation at the X chromosome. Therefore, MDX mice are usually used for MTT models of muscular dystrophy disease. Control mice, C57BL10/SCSN (B-10) were chosen as a source of normal myoblasts. Myoblasts isolated from the hindlimb muscle tissues of two- to three-day-old neonatal B-10 mice were cultured in vitro for one to seven days. Through our modifyied techniques of isolation and culturing conditions, a myoblast purity of 70% could be achieved, with fibroblast the only contaminating cell type. The proliferative capacity and the doubling time of myoblasts were counted from analysis of growth kinetics. While differentiative capacity was analyzed morphologically, we found the fusion of myoblasts was time-dependent. Immunostaining myoblasts of different stages with anti-dystrophin antibody showed that purified myoblasts with the capacity of fusion can express dystrophin and can be utilized as a donating source in MTT. In the MTT experiment, eight young MDX mice were injected with normal myoblasts at a concentration of 1 x 10(6) cells. All transplated mice received daily cyclosporine A injection for immunosuppression. Two to three months later, dystrophin was found in the myoblast-transferred muscles while staining immunocytochemically. The result suggests that we successfully transferred the normal dystrophin gene from the normal myoblasts into the MDX mice since their myoblast-injected muscle could express dystrophin.

Animals↗
PubMed1995

Dissociation of the restoration of copulatory behavior and the testicular morphology in old male rats with fetal brain grafting.

Improvement of copulatory activity has been reported in aged male rats bearing the fetal preoptic area (POA), however, whether the fetal POA graft has any effect on the gonad of aged male rats has not been established. In the present study, the testicular histology and the sexual behavior were studied in 20 old (18-19 months) Long-Evans male rats after fetal brain transplantation. Animals were divided into three groups: (1) POA-grafted group (n = 6): fetal POA neurons were grafted into the POA, (2) COR-grafted group (n = 7): fetal cerebral cortex tissue was grafted into the POA and (3) SHAM-grafted group (n = 7): the POA of rats received glucose-saline injection. Thirty days after the grafting, only those bearing POA graft showed an increase in mount frequency and intromission frequency. Sixty days after fetal brain grafting, testicular morphology was examined. Testicular volume was measured and paraffin sections (8 microns) of the testis were stained with Hematoxylin-Eosin. Seminiferous tubular diameter and epithelial height were analyzed quantitatively. No significant changes in testicular volume, seminiferous tubular diameter and epithelial height were observed in all three groups. The shrunk testicular morphology in the aged male rats cannot be restored by fetal POA grafting. These results suggest that copulatory behavior and testicular morphology may be dissociated in old male rats.

Aging↗
PubMed1994

Effects of estrogen and estrogen receptor in normal human melanocytes.

Normal human melanocytes were cultured selectively with F12 culture medium supplemented with growth hormones, phorbol ester and 1% of fetal calf serum. The estrogen receptors were analyzed using hydroxylapatite-column assay with tritiated 17-beta-estradiol as the binding ligand. Phenol red- free medium was used when the changes in cell numbers, melanin content and tyrosinase were assessed after incubating with physiological concentration of 17-beta estradiol (10(-12) and 10(-9) M). It was found that the melanocytes contained both cytosol (5.42 +/- 1.11 fmol/mg protein) and nuclear (59.13 +/- 17.12 fmol/mg protein) estrogen receptor. In response to estradiol, the cell number increased but both the melanin content and the tyrosinase activity decreased in a dose related pattern. These data suggested the presence of estrogen receptor with biological function in normal human melanocytes.

Animals↗
PubMed1994

The effect of hyperthermic treatment on electroencephalographic recovery after interruption of respiration in rats.

Electroencephalography (EEG) was utilized for investigating the effect of hyperthermia followed by apneic hypoxia in rats. They were heated whole-bodily to 41 degrees C for 15 min under the control of an artificial rodent ventilator, after drug-induced generalized paralysis. A transcutaneous oxygen saturation monitor was applied to detect the hypoxic condition. EEG was monitored with bipolar needle electrodes. The 72-kDa heat-shock protein (HSP72) in brain was analyzed by sodium dodecyl sulfate-polyacrylamide electrophoresis, followed by immunostaining with an anti-HSP72 antibody. There was no difference in the time interval from onset of apneic hypoxia to flat EEG between the hyperthermic and control groups, but cortical electrical activity appeared earlier in the hyperthermia group than the control group, after 90 s of ventilation interruption. The cardiac function did not change in the two groups. The HSP72 synthesis significantly increased in the brain of the rats with hyperthermic treatment.

Animals↗
PubMed1994

Changes of progesterone receptors in mesometrial and antimesometrial deciduoma after removal of fetus or placenta in unilateral pregnant hamster.

The effects of fetuses or placentas (with fetuses) removal on progesterone receptors (PR) in deciduomal tissues were investigated in unilateral pregnant (ULP) hamsters. Deciduomal reactions in response to artificial stimuli were induced on the tube-ligated uterine horns of ULP hamsters. Fetuses or placentas (with fetuses) were removed on day 8 of ULP, and the cytosolic and nuclear PR (cPR, and nPR, respectively) levels in deciduomal tissues at mesometrial (MS) and antimesometrial (AMS) sites were separately studied on day 10 and 12 of ULP. In the sham control group, cPR at the MS decreased with time, but at a slower rate than that at the AMS. The MS deciduoma contained higher cPR than the AMS deciduoma on day 12. Removal of fetuses did not cause any significant change of the decline rate, and the PR levels were similar to that of the control. The nPR at the MS and AMS also declined with time in all three groups. Removal of placentas induced drastic losses of cPR and nPR at the MS and AMS on day 10 and 12. Supplement of progesterone (P; 2 mg/animal/day) to the placenta-removed group restored the cPR somewhat at the MS site, but not back to the level of the control. The effect of P to restore nPR levels could be observed at the MS and AMS on day 10, but only at the MS on day 12. These data suggest that placental factor(s) other than P may play an important role on the maintenance of PR in deciduoma. Other cellular mechanisms may exist at the MS and AMS sites for the heterogeneous responses.

Animals↗
PubMed1994

Beneficial effect of prednisolone withdrawal followed by human lymphoblastoid interferon on the treatment of chronic type B hepatitis in Asians: a randomized controlled trial.

To evaluate the effect of interferon and the benefit of prednisolone pretreatment in Oriental patients with chronic active hepatitis B, 120 male Chinese patients were randomly allocated to receive: 1) group A: a 4-week course of prednisolone followed by 2 weeks of no treatment and then a 12-week course of human lymphoblastoid interferon, 4 to 6 MU/m2 intramuscularly; 2) group B: as group A, but with placebo given instead of prednisolone; 3) group C: an 18-week course of placebo. Clearance of serum hepatitis B virus-DNA and HBeAg (complete response) was achieved in 21% of group A, 5% of group B and none of group C at the end of therapy (A vs B: p = 0.054; A vs C: p < 0.01). When assessed 12 months after the end of therapy, the complete response rate was 46% in group A, 24% in group B and 25% in group C (p < 0.05). Those with baseline alanine transaminase < or = 200 U/l showed a better response to interferon following prednisolone withdrawal (48%) than with interferon therapy alone (20%, p = 0.056) and no treatment (9%, p < 0.01). Those with a baseline serum hepatitis B virus-DNA < or = 1000 pg/ml also showed a higher complete response rate when pretreated with prednisolone (59%) than when treated with interferon alone (29%, p = 0.084) or untreated (22%, p < 0.03). The strongest independent predictor of a response to treatment was prednisolone withdrawal (p < 0.05). None of the responders lost hepatitis B surface antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A new mutational hot-spot in the p53 gene in human hepatocellular carcinoma.

Mutations in the p53 gene are frequent genetic alterations in human hepatocellular carcinoma. We have examined 38 hepatocellular carcinoma cases from Taiwan for the presence of p53 alterations in exons 5-8 of the gene using the single-stranded conformational polymorphism method and direct sequencing of polymerase chain reaction products. Using the single-stranded conformational polymorphism method, we found mutations in 16 (42.1%) cases. Twelve mutations were found in exon 5, three in exon 7, and one in exon 8. No mutations were found in exon 6. Sequencing of polymerase chain reaction products showed that all mutations in exon 5 were clustered at codon 166 and were T/A transversions resulting in an amino acid change from serine to threonine, identifying a new hot-spot for point mutations in the p53 gene. The mutations in exon 7 were all at codon 249, and were G/T transversions leading to an amino acid change of arginine to serine. Finally, the mutation at exon 8 was a G-to-T transversion at codon 286 leading to a stop codon. These data indicate that mutations of the p53 gene may be important in the development of human hepatocellular carcinoma and that, in contrast to other tumors, the mutations of the p53 gene in hepatocellular carcinomas can be clustered in a specific codon of the gene.

Base Sequence↗
PubMed1994

Detection of hepatitis B and C viruses in liver tissue with hepatocellular carcinoma.

Polymerase chain reaction was used to investigate the presence of the hepatitis B and C viruses in liver tissue from Taiwanese patients with hepatocellular carcinoma by examining paired samples (tumor and non-tumor) from 38 cases. We used a DNA-polymerase chain reaction protocol with primers spanning the regions of the hepatitis B virus genome corresponding to HBs, HBc, and HBx genes and RNA-polymerase chain reaction protocol with primers spanning the 5' untranslated region of the hepatitis C virus. Co-infection with hepatitis B and hepatitis C viruses was seen in nine patients (23%), only three of whom had anti-hepatitis C virus in serum. One of these three was HBsAg-negative in serum while the other two and four of the other six from this group were HBsAg-positive. One of the patients with anti-HCV and no HBsAg in serum had no hepatitis C virus-RNA in liver tissue, while hepatitis B virus-DNA was detectable by using the HBc and HBx specific primers. We detected hepatitis C virus as a single agent in the liver in only one patient. This patient was anti-HCV positive and HBsAg-negative. The remaining 27 patients (71%) had infection with hepatitis B virus only. Twenty-five of 27 patients had HBsAg in their sera. HBs-specific primers detected hepatitis B virus-DNA in non-tumor tissue from 23 patients and in tumor tissue from 25 patients. HBc-specific primers detected hepatitis B virus-DNA in non-tumor tissue from 24 patients and in tumor tissue from 20 patients. Finally, HBx-specific primers detected hepatitis B virus-DNA in non-tumor tissue from 24 patients and in tumor tissue from 25 patients. These data indicate that in a hyperendemic area, hepatitis B virus is closely associated with the development of hepatocellular carcinoma but that infection with hepatitis C virus may play a secondary role.

Carcinoma, Hepatocellular↗