Association study of NlaIII and MspI genetic polymorphisms of catechol-O-methyltransferase gene and susceptibility to schizophrenia.
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Biomedical subjects
Publications and source records attributed to Y R Lee.
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Recent studies have reported an association between a 102T/C polymorphism of serotonin receptor type 2A gene (5-HT2A) and schizophrenia. In addition, an association was detected between a 102T/C polymorphism of the 5-HT2A receptor gene and drug response to clozapine in the treatment of schizophrenic patients. These studies suggest an important role of the 5-HT2A gene in schizophrenia. To study the possible involvement of the 5-HT2A gene in the pathogenesis of schizophrenia, a case-control association study was carried out in a Chinese population from Taiwan. No significant differences of genotype distributions, allele frequencies and homozygosity were detected between schizophrenic patients (n = 177) and nonpsychiatric controls (n = 98). When subjects were divided into subgroups according to sex, still no differences of allele frequencies or genotype distributions were noted between patients and controls. Our data do not support an allelic association between the 102T/C polymorphism of the 5-HT2A receptor gene and schizophrenia in Chinese population.
The study examined differences in motivations for parent care of Korean caregivers and Caucasian American caregivers of elderly parents with dementia. A number of American caregivers, mostly daughters of the demented parents, had affectionate relationships with their parents, but they expressed a relatively low degree of filial responsibility. In contrast, among Korean caregivers, the care of demented parents was predominantly the responsibility of daughters-in-law who were less likely to have affectionate relationships with the parents-in-law. However, Korean caregivers expressed a significantly higher level of filial responsibility than the American caregivers. Some cultural differences between the two ethnic groups associated with parent care were discussed.
Several linkage studies suggested chromosome 22q11-13 may harbor susceptible genes for schizophrenia. Catechol-O-methyl-transferase (COMT), which is involved in the metabolism of catecholamines, was mapped to 22q11 and is considered a possible candidate gene for schizophrenia. Recently, we identified a polymorphic marker, a single nucleotide C insertion at the 3' untranslated region of the COMT gene, which obliterates a BglI site. Using this BglI polymorphism, we conducted a case-control association study in Chinese patients with schizophrenia. No significant differences of allele and genotype frequencies were noted between patients (N = 177) and controls (N = 99). When patients were subgrouped according to sex, no significant differences of genotype and allele frequencies were noted in either male or female patients compared to normal controls. Our results do not support an association between the BglI polymorphism of COMT gene and schizophrenia.
In the present experiments, we measured N-methyl-D-aspartate (NMDA)-induced norepinephrine (NE) release and extracellular action potentials in the cerebellar cortex of urethane-anesthetized rats. The overflow of NE was measured using a Nafion coated-carbon fiber electrode and in vivo chronoamperometry. We found that both NMDA and quisqualate evoked NE release. Our previous work demonstrated that the electrophysiological activity of cerebellar Purkinje neurons could be either excited or inhibited by local NMDA application. It was reported that bicuculline antagonized NMDA-induced inhibition in Purkinje neurons, suggesting that a GABAergic mechanism was activated during NMDA application. We and others previously found that GABA-mediated electrophysiological depressions were enhanced by NE acting via beta-adrenergic receptors while these responses were decreased by activation of alpha-adrenergic receptors. Since NMDA evokes overflow of endogenous NE, the electrophysiological depression induced by NMDA may contain an NE-mediated modulatory component. In this study, we first examined the interaction of NMDA with beta-adrenergic agonist. We found that local application of isoproterenol facilitated NMDA- or GABA-mediated electrophysiological depressions of the Purkinje neurons. Applications of phenoxybenzamine, which antagonized the alpha-adrenergic response of synaptically released NE, also facilitated NMDA-elicited depression. In contrast, the depression induced by GABA, which did not induce NE overflow, was not potentiated by phenoxybenzamine. The facilitation of NMDA-induced depression by phenoxybenzamine was antagonized by the beta-adrenergic antagonist timolol. Taken together, these data suggested that the nonadrenergic pathway is involved in NMDA-induced electrophysiological responses in the cerebellum. NMDA may induce neuronal depression through modulation of GABAergic inhibition via NMDA-evoked NE release onto cerebellar Purkinje neurons.
Wound contraction is an important event that minimizes the wound defect during the healing process. Involvement of insulin-like growth factor (IGF)-I and IGF-binding protein (IGFBP)-1 in wound contraction was studied using an in vitro model. Human dermal fibroblasts (1 x 10(5) cells/ml) were incorporated into a porcine type I collagen (0.21% final) in serum-free medium. The fibroblast-embedded collagen gels in a 12-well plate were floated from the well, and various reagents were then added to the assay medium. The surface area of the gel was calculated by measuring the diameters of the collagen gel. IGF-I at high doses (30 and 100 ng/ml) revealed 6.8% (P < 0.01) and 7.7% (P < 0.001) gel contraction, respectively, and des (1-3) IGF-I at 10 ng/ml produced a 4.5% gel contraction (P < 0.01). Meanwhile, IGFBP-I did not induce any significant contraction throughout the tested concentrations (0.1-100 ng/ml). A combination of IGF-I and IGFBP-1 at 1 ng/ml of each reagent, a concentration at which gel contraction was not observed when each of the reagents was tested individually, produced a 14% gel contraction (P < 0.001), whereas combinations of des (1-3) IGF-I with IGFBP-1 at the same concentrations did not promote gel contraction. The increased IGFBP-I doses in combination with 1 ng/ml IGF-I tended to enhance the gel contraction. IGF-I- and IGFBP-1-induced gel contraction was prominent during the initial 12-h incubation period. When anti-IGF-I, anti-IGFBP-1, or anti-IGF-I receptor antibody was added to the assay medium before the addition of IGF-I and IGFBP-1, the IGF-I- and IGFBP-1-induced gel contraction was significantly suppressed (P < 0.001). Endothelin-1, a vasoconstrictor peptide that is known to promote fibroblast-embedded collagen gel contraction, appeared to be partially involved in the IGF-I- and IGFBP-1-induced gel contraction, because the addition of an endothelin receptor antagonist (Bosentan or BE-18257B at 1 microg/ml) moderately suppressed the IGF-I- and IGFBP-1-induced gel contraction (P < 0.01). On the other hand, when IGF-I and IGFBP-1 were applied with endothelin-1 (1 nM), an enhanced gel contraction (29.4%) was observed that was significantly greater than that induced by either individually (P < 0.001). These results clearly indicate that the combination of IGF-I and IGFBP-1 promotes fibroblast contraction in collagen gel, and that this phenomenon is caused by IGFBP-1's strong potentiation of the IGF-I-induced gel contraction.
A cDNA clone encoding a 101-kD heat shock protein (HSP101) of soybean was isolated and sequenced. Genomic DNA gel blot analysis indicated that the corresponding gene is a member of a multigene family. The mRNA for HSP101 was not detected in 2-day-old etiolated soybean seedlings grown at 28 degrees C but was induced by elevated temperatures. DNA sequence comparison has shown that the corresponding gene belongs to the Clp (caseinolytic protease) (or Hsp100) gene family, which is evolutionarily conserved and found in both prokaryotes and eukaryotes. On the basis of the spacer length between the two conserved ATP binding regions, this gene has been identified as a member of the ClpB subfamily. Unlike other Clp genes previously isolated from higher plants, the expression of this soybean Hsp101 gene is heat inducible, and it does not have an N-terminal signal peptide for targeting to chloroplasts. Transformation of the soybean Hsp101 gene into a yeast HSP104 deletion mutant complemented restoration of acquired thermotolerance, a process in which cells survive an otherwise lethal heat stress after they are given a permissive heat treatment.
In sabellid polychaetes the vitelline envelopes, in which microvilli with glycocalyx structures at the tips are invested, change in structure during oogenesis. Vitelline envelopes isolated from Schizobranchia oocytes 25-100 micron and 160-185 micron in diameter, were analyzed in protein components by iodination, electrophoresis, Western blotting and radioactive labeling technique. The observations demonstrate that the membrane proteins of the vitelline envelopes are not consistent but variable in components during oogenesis. Most of these proteins, particularly the high molecular weight proteins, are PAS-positive glycoproteins, which may have specific carbohydrate residues binding to wheat germ agglutinin. The proteins could be labeled with [3H]valine within 36 h by incubating the whole oocytes in sea water to a high level, indicating that the proteins are actively synthesized by the growing oocytes. Synthetic rates of the proteins differ from each other at one stage and are higher in the small than in the large oocytes in general, suggesting that the membrane proteins are involved in the function of the vitelline envelopes during oogenesis.
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Solid and papillary epithelial neoplasm of the pancreas is a low-grade malignant tumor, generally occurring as a slowly growing upper abdominal mass in a young female. With complete excision, the prognosis is good. Malignant behavior with metastasis does occur, but the incidence is very low. We report a young woman who had this neoplasm in the pancreatic tail with peritoneal seeding and its recurrence.
BACKGROUND: We assessed the postoperative findings of proximal gastrectomy and jejunal pouch interposition with contrast radiography. METHODS: Eleven patients with proximal gastrectomy and jejunal pouch interposition for proximal gastric carcinoma underwent contrast radiography. We evaluated the radiographic findings of the remnant stomach and interposed jejunal pouch. RESULTS: The interposed jejunal pouch showed good expansion, and the motility of the remnant gastric antrum was normal in all patients. One patient had significant lumenal narrowing of the esophageal pouch anastomotic site. Leak at the anastomotic site was not found. Reflux into the esophagus from the pouch was observed in two patients. Gastric emptying time was considerably delayed in two patients. CONCLUSION: Follow-up upper gastrointestinal series of the proximal gastrectomy and jejunal pouch interposition showed different postoperative findings. Awareness of the normal and abnormal findings is essential in the accurate postoperative evaluation of these patients.
Endocrine therapy is effective in approximately one-third of all breast cancers and up to 80% of tumors that express both estrogen and progesterone receptors. Despite the low toxicity, good overall response rates, and additional benefits associated with its partial agonist activity, most Tamoxifen-responsive breast cancers acquire resistance. The development of new antiestrogens, both steroidal and non-steroidal, provides the opportunity for the development of non-cross-resistant therapies and the identification of additional mechanisms of action and resistance. Drug-specific pharmacologic mechanisms may confer a resistance phenotype, reflecting the complexities of both tumor biology/pharmacology and the molecular endocrinology of steroid hormone action. However, since all antiestrogens will be effective only in cells that express estrogen receptors (ER), many mechanisms will likely be directly related to ER expression and signaling. For example, loss of ER expression/function is likely to confer a cross-resistance phenotype across all structural classes of antiestrogens. Altered expression of ERalpha and ERbeta, and/or signaling from transcription complexes driven by these receptors, may produce drug-specific resistance phenotypes. We have begun to study the possible changes in gene expression that may occur as cells acquire resistance to steroidal and non-steroidal antiestrogens. Our preliminary studies implicate the altered expression of several estrogen-regulated genes. However, resistance to antiestrogens is likely to be a multigene phenomenon, involving a network of interrelated signaling pathways. The way in which this network is adapted by cells may vary among tumors, consistent with the existence of a highly plastic and adaptable genotype within breast cancer cells.
Novel fluorocyclopropanoid nucleosides were designed, synthesized and evaluated their antiviral activities against poliovirus, HSV, HIV, and HBV.
PURPOSE: The purpose of this study was to evaluate the radiological features of 12 pathologically proven cases of colorectal leiomyomatous tumors. METHOD: A retrospective analysis of radiologic findings was performed in 12 patients with pathologically proven colorectal leiomyomatous tumors (2 leiomyomas and 10 leiomyosarcomas). Available radiologic studies included abdominal CT scans in 11 patients, double contrast barium studies in 4, and pelvic MRI in 1. On imaging, we evaluated the size, tumor margin (smooth or lobulated), morphologic appearance, growth patterns (endocolic, exocolic, or combined), contrast enhancement patterns, presence or absence of calcification within the tumors, and metastasis. RESULTS: The involved tumor sites were the colon in 2 patients and the rectum in 10. The mean tumor size was 7.9 cm (range 2-15 cm): It was 3.5 cm in leiomyomas and 8.8 cm in leiomyosarcomas. On imaging studies, the tumor margin was smooth in three patients and lobulated in nine, with endocolic growth in one, exocolic in four, and combined in the remaining seven. Eight of the 12 tumors showed varying degrees of internal necrosis with heterogeneous contrast enhancement. Dystrophic calcification was noted in five patients. Metastasis was seen in the liver in three patients at the time of initial diagnosis, and lymphadenopathy was noted in two patients (paraaortic space in one and perirectal space in two). CONCLUSION: Although rare, the diagnosis of leiomyomatous tumor may be suggested especially when the tumor occurring in the colorectum shows exocolic growth or calcification with varying degree of internal necrosis.