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Biomedical subjects

C Hsu

Publications and source records attributed to C Hsu.

At least 91 records · Page 5Linked to original sources
PubMed1995

The role of T cell receptor beta chain genes in susceptibility to rheumatoid arthritis.

OBJECTIVE: To evaluate the role of the T cell receptor beta chain locus (TCRB) in genetic susceptibility to rheumatoid arthritis (RA). METHODS: Twenty-eight multiplex RA families were recruited from 3 rheumatology outpatient departments. All members were genotyped for a highly informative microsatellite (V beta 6.7), a V beta 12.2 SSCP marker, and a biallelic C beta restriction fragment length polymorphism. Data were analyzed by the SIBPAL program to assess identity-by-descent in affected sib-pairs. RESULTS: Using the V beta 12.2 marker, there was suggestive evidence of increased sib-pair sharing (P = 0.005) in affected offspring (a P value of 0.001 is generally taken to establish linkage). Data for V beta 6.7 and C beta yielded significance levels of 0.06 and 0.19, respectively. CONCLUSION: These data suggest that a gene in or linked to the TCRB complex may confer genetic susceptibility to RA in these families. Confirmation in a larger panel of families is required.

Adolescent↗
PubMed1995

Non-linkage of a T-cell receptor gamma chain microsatellite (D7S485) to rheumatoid arthritis in multiplex families.

A highly informative microsatellite marker, D7S485, from the T-cell receptor gamma (TCRG) locus, has been used to study segregation of TCRG genes in 26 multiplex rheumatoid arthritis (RA) families. We used the sib-pair method to assess excess identity-by-descent sharing among affected members in these families and the LINKAGE package of programs was used to calculate two-point lod scores for the D7S485 marker. There was no evidence for segregation of TCRG genes with RA in affected siblings and significantly negative lod scores were obtained from linkage analyses using both autosomal dominant and recessive models of inheritance.

Adolescent↗
PubMed1995

The first intron of the mouse neurofilament light gene (NF-L) increases gene expression.

Neurofilament expression is developmentally and post-transcriptionally controlled. Using transient transfection assays in mouse L cells, we demonstrate that the expression of the mouse neurofilament light subunit (NF-L) is influenced by intron sequences. NF-L expression was decreased twenty fold upon deletion of the three intron sequences. Elements contained principally within a 350 bp region of intron 1 were responsible for enhanced NF-L expression. Enhancement of expression did not occur when intron I was placed 3' to a heterologous chloramphenicol acetyl transferase (CAT) gene whose expression was driven by NF-L 5' sequences. The intron enhancement of NF-L expression was not promoter-specific and also occurred with the mouse sarcoma virus (MSV) LTR promoter. These data suggest intron sequences may be important in regulating NF gene expression.

Animals↗
PubMed1995

Clinical risk factors for pulmonary barotrauma: a multivariate analysis.

Previous investigations have suggested that elevated airway pressures increase the risk of ventilator-induced pneumothorax. However, risk factor analysis using multivariate techniques has not been done. We investigated the hypothesis that airway pressures would not independently correlate with pneumothorax when underlying disease was considered. All ventilated patients over a 1 yr period in the Hohenburg Critical Care Unit at the University of Alabama were followed until death or discharge from the ICU. Ventilator data were collected daily and the presence of pneumomediastinum and pneumothorax determined by review of chest radiographs. Maximal values of airway pressures, minute ventilation, tidal volume, and respiratory rate, as well as age, sex, and underlying disease, were entered into logistic regression analysis. A total of 168 patients was studied, and 20 experienced pneumothorax. Multivariate analysis of the entire ventilated population revealed that only the presence of ARDS independently correlated with pneumothorax. A similar analysis performed on the ARDS population revealed independent correlation only with male sex. Trends toward elevation in airway pressures were seen that did not reach statistical significance. We conclude that development of pneumothorax is most closely correlated with underlying disease, specifically ARDS, and that the associations previously noted between airway pressures and barotrauma largely relate to the occurrence of high airway pressures in ARDS.

Adult↗
PubMed1995

[Effect of pinealectomy on N-methyl-D-aspartate-facilitated receptivity in female rats].

The purpose of this study was to examine the effect of pinealectomy and the possible mechanism of the pineal gland on N-methyl-D-aspartate (NMDA)-associated receptivity in female rats. Monosodium L-glutamate (MSG) was used as a neurotoxin to induce hypogonadal status. Long-Evans rats were divided into four groups: (1) control (C), (2) pinealectomized (Px), (3) MSG-treated (MSG) and (4) pinealectomized MSG-treated (Px-MSG). Two injections of MSG were administered on the first and the third days postnatally with a dose of 4 mg/g body weight. Pinealectomy was performed at six weeks of age. In the first part of the experiment, all four groups of rats were ovariectomized at 3.5 months and implanted subcutaneously with a 2mm silastic capsule filled with 20% estradiol benzoate (EB). One week later, the sexual receptivity was estimated by lordosis quotient (LQ) before and ten minutes after 20 mg/kg B.W. NMDA administration. The result shows that NMDA caused a remarkable increase of LQ in control rats, but no significant effect on MSG-treated rats. There was no significant difference between control and Px rats before NMDA administration, but Px rats exhibited higher LQ than control rats after NMDA treatment. In the second part of the experiment, the effect of pinealectomy on releasability of LHRH neurons was examined indirectly by NMDA-evoked LH secretion. The dosage and sampling schedule were chosen by the dose-response and time course of LH response to NMDA, respectively. Serum samples were collected before and ten minutes after NMDA administration. Serum concentration of LH was measured by radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Over-representation of the disease associated (CAG) and (CGG) repeats in the human genome.

Expansion of trimer repeats has recently been described as a new type of human mutation. Of the 64 possible trimer compositions, only the CGG and CAG repeats have been implicated in genetic diseases. This study intends to address two questions: (1) What makes the CGG and CAG repeats unique? (2) Could other trimer repeats be involved in this type of mutation? By computer analysis of trimer and hexamer frequency distributions in approximately 10 Mb of human DNA, twenty trimer motifs (ten complementary pairs) have been identified that are the most likely to be expanded. The frequency distribution study also indicated that the expanded trimer motif in Fragile-X syndrome is GGC instead of CGG. DNA linguistics studies revealed that the GGC/GCC and CAG/CTG repeats were over-represented in the human genome. Further analysis of base composition suggested that the CCA/TGG repeats may be involved in the trimer expansion mutation since they possessed many similar characteristics to GGC/GCC and CAG/CTG. The computer aided sequence analysis studies reported here may help to understand the molecular mechanisms of trimer repeat expansion.

Base Sequence↗
PubMed1994

Selection of antisense oligonucleotides on the basis of genomic frequency of the target sequence.

Antisense oligonucleotides (ASOs) are capable of blocking the expression of targeted genes and are potential antitumor and antiviral therapeutic agents. The specificity of ASO gene inhibition is compromised when homology to other sequences allows the selected ASO to bind to nontargeted mRNAs. To reduce this nonspecific activity, an ASO should target a sequence that is predicted to be unlikely to occur in other mRNAs. The probability of a sequence being unique can be predicted by determining the genomic frequency of short stretches of sequences contained within the target sequence. Two computer programs, OLIGOMER and HEXAGRAPH, were developed for this analysis. OLIGOMER was used to analyze the genomic frequencies of di-, tri-, and hexamers in more than 24 million nucleotides from 8 different genomes in GenBank. A mathematical model was developed that predicts the genomic frequency of longer oligomers on the basis of the observed frequencies of shorter oligomers. The second program, HEXAGRAPH, was used to graphically display the genomic frequency data of a selected target gene. The computational tools developed in this study may help to design more efficient ASOs by decreasing their nonspecific binding activity.

Animals↗
PubMed1994

Differential growth kinetics are exhibited by human immunodeficiency virus type 1 TAR mutants.

The human immunodeficiency virus type 1 (HIV-1) TAR element is critical for the activation of gene expression by the transactivator protein, Tat. Mutagenesis has demonstrated that a stable stem-loop RNA structure containing both loop and bulge structures transcribed from TAR is the major target for tat activation. Though transient assays have defined elements critical for TAR function, no studies have yet determined the role of TAR in viral replication because of the inability to generate viral stocks containing mutations in TAR. In the current study, we developed a strategy which enabled us to generate stable 293 cell lines which were capable of producing high titers of different viruses containing TAR mutations. Viruses generated from these cell lines were used to infect both T-lymphocyte cell lines and peripheral blood mononuclear cells. Viruses containing TAR mutations in either the upper stem, the bulge, or the loop exhibited dramatically decreased HIV-1 gene expression and replication in all cell lines tested. However, we were able to isolate lymphoid cell lines which stably expressed gene products from each of these TAR mutant viruses. Though the amounts of virus in these cell lines were roughly equivalent, cells containing TAR mutant viruses were extremely defective for gene expression compared with cell lines containing wild-type virus. The magnitude of this decrease in viral gene expression was much greater than previously seen in transient expression assays using HIV-1 long terminal repeat chloramphenicol acetyltransferase gene constructs. In contrast to the defects in viral growth found in T-lymphocyte cell lines, several of the viruses containing TAR mutations were much less defective for gene expression and replication in activated peripheral blood mononuclear cells. These results indicate that maintenance of the TAR element is critical for viral gene expression and replication in all cell lines tested, though the cell type which is infected is also a major determinant of the replication properties of TAR mutant viruses.

Base Sequence↗
PubMed1993

The facilitatory effect of N-methyl-D-aspartate on sexual receptivity in female rats through GnRH release.

The purpose of this study was to examine whether N-methyl-D-aspartate affects the sexual receptivity of female rats. Monosodium L-glutamate was used as a neurotoxin to induce hypogonadal status. Matured normal and monosodium L-glutamate-treated rats were ovariectomized and implanted subcutaneously with estradiol capsules. One week later, lordosis responsiveness was observed before and 10 min after N-methyl-D-aspartate (40 mg/kg of BW, ip) administration. The results showed that N-methyl-D-aspartate caused a remarkable increase of lordosis quotient in control rats but not in monosodium L-glutamate-treated rats. Moreover, the possible action site of N-methyl-D-aspartate in the enhancement of receptivity was evaluated by the post-castrational LH rise, pituitary LH release in response to GnRH, and N-methyl-D-aspartate-evoked GnRH releasability. The results revealed that: (a) serum levels of LH in monosodium L-glutamate-treated rats were lower (p < 0.01) than those of control rats after ovariectomy; (b) there was no significant difference of pituitary LH release responsiveness to GnRH test between two groups; and (c) N-methyl-D-aspartate-evoked LH release in monosodium L-glutamate-treated rats was similar to that in the control rats. In conclusion, N-methyl-D-aspartate may facilitate the sexual receptivity through stimulating GnRH release. The failure of N-methyl-D-aspartate in enhancing receptivity in monosodium L-glutamate-treated rats is probably due to the cellular damage by monosodium L-glutamate on specific areas responsible for lordosis.

Animals↗
PubMed1993

Effects of long-term estradiol exposure on the hypothalamic neuron number.

Neuron density, volume of the area and total neuron number were measured in the medial preoptic area, anterior hypothalamic area and arcuate nucleus of the hypothalamus of young (6-month-old), middle age (14-month-old) and old (22-month-old) male and female rats. Intact male rats did not show neuron loss even in old age, while intact female rats manifested neuron loss in the medial preoptic area, anterior hypothalamic area and arcuate nucleus in old age. Long-term administration of estradiol benzoate to castrated male rats induced neuron loss in the anterior hypothalamic area and arcuate nucleus of the middle age group and in all three areas of the old age group. However, long-term ovariectomy could not prevent neuron loss in these hypothalamic areas in old age. The results suggested that estradiol can have a cumulative impact on the degree of neuron damage and simulate female-type age-related neuron loss in male rats and that there may be the possibility of an intrinsic aging process inducing neuron loss in female rats.

Animals↗
PubMed1993

[The mechanism of the pineal gland in inhibiting sexual receptivity of female rats treated with monosodium-L-glutamate: (III). Does it concern with the function of the pituitary gland?].

To elucidate whether pituitary function participates in the effect of the pineal gland on sexual receptivity, monosodium L-glutamate (MSG) was used as a neurotoxin to induce hypogonadal status. Long-Evans rats were divided into four groups: (1) normal control (C), (2) pinealectomized (Px), (3) MSG-treated (MSG) and (4) pinealectomized MSG-treated (Px-MSG). Pinealectomy was performed at six weeks of age. In the first part of the experiment, the sexual receptivity was estimated at the age of 2.5 months by lordosis quotient (LQ). The result indicates that the decline of receptivity by neonatal MSG treatment can be significantly improved by pinealectomy. In the second part of the experiment, the effect of pinealectomy on pituitary function was examined by two tests including (1) post-castrational LH rise and (2) pituitary response to LHRH. Ovariectomy was performed at the age of 2.5 months. Four weeks later three consecutive blood samples were collected at 10 minute intervals for LH radioimmunoassay. Then, three doses of LHRH (100 ng, 250 ng and 500 ng/100 g of body weight) were administered separately at two-week intervals, serum samples were taken before as well as 15 and 60 minutes after LHRH administration. The results showed that there was no significant difference in serum LH levels between Px and control rats after ovariectomy. The LHRH-evoked LH elevation in Px-MSG rats was just the same as that of the MSG rats, although the LH level in MSG rats was lower than in the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of anterior roof deafferentation on lordosis behavior and estrogen receptors in various brain regions of female rats.

This study investigated whether the estrogen receptors (ER), located at different brain areas and anterior pituitary (AP), changed after anterior roof deafferentation (ARD), and on the effects of facilitating the lordosis reflex in female rats. Female rats were ovariectomized and implanted with estradiol capsules. ARD or sham operation was performed with a Halász knife. All animals were tested for lordosis both before and after surgery. One day after the last test they were sacrificed. Cytosol and nuclear ER in the AP, medial preoptic area (MPOA), basal medial hypothalamus (BMH), amygdala (AMYG), septum (SEP), hippocampus (HPC), and cortex (CTX) were measured using an in vitro exchange assay. Rats with ARD showed significantly higher mean levels of lordosis quotient than the control and the sham groups before ARD surgery. An increase of both cytosol and nuclear ER in the BMH area compared to the control was observed, whereas the ER, in the SEP was reduced. ER in other areas were not affected by ARD. Serum estradiol and progesterone levels were not altered by the operation. These data suggest that the dorsal inhibitory pathway from the extrahypothalamus to the preoptic area and hypothalamus may modulate the estrogen receptor and the display of lordosis in female rats. Change of ER level in the BMH area may influence the hormonal sensitivity of lordosis in female rats.

Animals↗