Biomedical subjects

S Harada

Publications and source records attributed to S Harada.

At least 37 records · Page 2Linked to original sources

PubMed2001

Linked polymorphisms (-333G>T and -286A>G) in the promoter region of the CCK-A receptor gene may be associated with schizophrenia.

Cholecystokinin A receptors (CCKAR) modulate CCK-stimulated dopamine release, and mutations in the CCKAR gene may predispose affected individuals to schizophrenia. Our previous study suggested that -286A>G polymorphism (previously named 201A>G) in the CCKAR gene promoter is associated with schizophrenia. In the present study, we carried out a further investigation of the promoter and intron 1 of the CCKAR gene. In addition to polymorphisms reported previously (-333G>T, -286A>G, -241G>A, 773A>T, and 779T>C), two novel polymorphisms (-388(GT)(8)>(GT)(9) and -85C>G) were identified. These polymorphisms were in a linkage disequilibrium. Association analyses between schizophrenic patients and controls revealed that the frequencies of the A allele and AA genotype at the -286 loci, as well as the frequency of the GG genotype at the -333 loci, were significantly higher in patients than in controls. Furthermore, patients with paranoid type schizophrenia, auditory hallucinations, or a positive family history had a significantly higher frequency of the -286A allele than the control group. The results supported our previous data, and suggest the possible involvement of the -333G>T and the -286A>G polymorphisms in the promoter region of the CCKAR gene in the predisposition to schizophrenia.

Adult↗

PubMed2001

The (CTG)n polymorphism in the NOTCH4 gene is not associated with schizophrenia in Japanese individuals.

BACKGROUND: The human NOTCH4 gene is a candidate gene for schizophrenia due to its chromosomal location and neurobiological roles. In a British linkage study, NOTCH4 gene polymorphisms were highly associated with schizophrenia. In a Japanese case-control association study, however, these polymorphisms did not show significant associations with schizophrenia. We conducted a case-control study with Japanese subjects to explore an association between the triplet repeat polymorphism in the NOTCH4 gene and schizophrenia, including subtypes of schizophrenia, longitudinal disease course characteristics, and a positive family history for psychoses. METHODS: We examined the (CTG)n repeat polymorphism in the NOTCH4 gene among 100 healthy Japanese individuals and 102 patients with schizophrenia (22 paranoid, 38 disorganized, 29 residual, 64 episodic, 31 continuous, 42 with prominent negative symptoms, and 46 with positive family histories) using a polymerase chain reaction-based, single-strand conformational polymorphism analysis. RESULTS: Five different alleles consisting of 6, 9, 10, 11, and 13 repeats of CTG (Leu) in patients with schizophrenia, and 4 alleles consisting of 6, 9, 10, and 11 repeats in controls were found. No significant differences in genotype or allele frequencies of repeat numbers were found between controls and patients. In addition, there were no associations between the polymorphism and schizophrenia subtypes, longitudinal disease course characteristics, or positive family history of the patients. CONCLUSIONS: Our data suggest a lack of association between the NOTCH4 gene triplet repeat polymorphism and schizophrenia in Japanese individuals.

Adult↗

PubMed2001

Enhanced infection of an X4 strain of HIV-1 due to capping and colocalization of CD4 and CXCR4 induced by capsianoside G, a diterpene glycoside.

We investigated whether capsianosides, diterpene glycosides, extracted from Capsicum plants could affect human immunodeficiency virus type 1 (HIV-1) infection. Significant effect on virus infection in MAGI/CCR5 cells was neither observed for the X4 virus by capsianosides II, XI, and A, nor for an R5 virus by capsianoside G. Apparent enhancement of X4 HIV-1 infection by capsianoside G was observed and exclusively related to the usage of the CXCR4 coreceptor. The capsianoside G-treated cells had no change in the expression level of CD4, CXCR4, and CCR5, however, colocalization and capping of CD4 and CXCR4, but not of CD4 and CCR5 was observed. Our results suggested that capsianoside G enhanced X4 virus infection at the level of viral penetration through the capping and colocalization of receptors needed for infection.

Adsorption↗

PubMed2001

Long-term exposure of tumor necrosis factor alpha causes hypersensitivity to androgen and anti-androgen withdrawal phenomenon in LNCaP prostate cancer cells.

BACKGROUND: One of the mechanisms through which prostate cancers relapse during anti-androgen therapy may involve adaptation to low concentrations of androgen induced by anti-androgen therapies. Recent studies from our laboratory have reported that tumor necrosis factor-alpha (TNFalpha) is secreted from prostate cancer epithelial cells and LNCaP cells. We hypothesized that TNFalpha changes androgen-sensitivity in LNCaP cells. METHODS: We cultured LNCaP cells for more than 3 months in the presence of 50 ng/ml TNFalpha and established TNFalpha-resistant LNCaP cells (LN-TR2). Sensitivity to androgen was examined by the cell proliferation assay. We also transfected LNCaP and LN-TR2 cells with a luciferase reporter plasmid driven by prostate-specific antigen (PSA) promoter and compared PSA promoter activity. Nuclear localization of AR protein that binds to target genes was also examined by Western blotting. RESULTS: LN-TR2 cells had increased sensitivity to dihydrotestosterone (DHT) (i.e., proliferation and PSA promoter activation) than LNCaP cells. Total AR mRNA and AR protein levels were decreased in LN-TR2 cells. However, LN-TR2 cells demonstrated increased levels of nuclear AR compared to LNCaP cells. At 1 nM DHT, the anti-androgen bicalutamide stimulated LN-TR2 and inhibited LNCaP proliferation. CONCLUSIONS: Long-term exposure of TNFalpha causes hypersensitivity to DHT in LNCaP and this was associated with increased nuclear AR protein. Furthermore, hypersensitivity to androgen caused anti-androgen withdrawal phenomenon in the presence of DHT although bicalutamide itself did not stimulate LNCaP proliferation without androgen. This result may be one possible mechanism for the anti-androgen withdrawal phenomenon.

Androgen Antagonists↗

PubMed2001

[Long-term survival of hormone-refractory prostate cancer: a case report].

Although prostate cancer initially responds well to endocrine therapy, it becomes resistant to the therapy a few years later, and is called hormone-refractory cancer. In general, hormone-refractory prostate cancer is resistant to all kinds of therapy and the prognosis is extremely poor. Here we report an unusual case of a person with hormone-refractory prostate cancer, who has been surviving for more than 5 years after being diagnosed as having this type of cancer. A 75-year-old man was diagnosed with prostate cancer (poorly differentiated adenocarcinoma, T3 N0 M1, stage D2) and initial endocrine therapy combined with castration and estrogen was effective. Four years later, the tumor marker of prostate-specific antigen (PSA) increased and the cancer was thought to be hormone-independent, refractory state. Alteration of antiandrogen from chlormadinone acetate to flutamide was effective and PSA was kept at low levels for 6 months. When PSA rose again, we started oral chemotherapy with tegafur.uracil. PSA decreased to normal range (complete response) and remained stable for 10 months. After that, a rapid increase of PSA was controlled for 7 months by oral chemotherapy with estramustine phosphate sodium and VP-16. This case indicates that alteration of antiandrogens or oral chemotherapy may be useful in some cases with hormone-refractory prostate cancer.

Adenocarcinoma↗

PubMed2001

Association of a 27-bp repeat polymorphism in ecNOS gene with ischemic stroke in Chinese patients.

OBJECTIVE: To investigate the association between a 27-bp repeat polymorphism of the ecNOS gene in 364 patients with ischemic stroke and 516 control subjects. BACKGROUND: The incidence of stroke in China is higher than that of coronary artery disease. Furthermore, ischemic stroke is more prevalent than hemorrhagic stroke. A 27-bp repeat polymorphism in intron 4 of the endothelial constitutive nitric oxide synthase (ecNOS) gene has been reported to associate with coronary artery disease in an Australian population, but no association was found between this polymorphism and ischemic stroke in a Japanese population. METHODS: All patients and unrelated control subjects were screened by CT. All participants lived in central China. Multivariate logistic regression analysis was used to determine the independent roles of this ecNOS gene polymorphism and covariates in ischemic stroke. RESULTS: These results indicated an association between the ecNOS a allele and ischemic stroke in the Chinese patients studied (7.8 versus 17.0%; OR = 2.44; 95% CI = 1.60 to 3.71, p < 0.0001). CONCLUSION: The ecNOS a allele in intron 4 may be an independent risk factor for ischemic stroke in the Chinese population studied, especially in those lacking other conventional risk factors.

Aged↗

PubMed2001

Glutathione S-transferase M1 gene deletion may be associated with susceptibility to certain forms of schizophrenia.

Recent studies have revealed that GSTM1 and M2 of the mu-class glutathione S-transferases catalyze a glutathione conjugate of catechol o-quinones including dopachrome, noradrenochrome, and adrenochrome under physiological conditions. Reduced or negative levels of activity amongst these enzymes would lead to an excess of neurotoxic compounds of catecholamine o-quinones. A defect in the mechanisms responsible for this form of detoxification may contribute to the development of certain forms of schizophrenia. We have performed a case-control study to explore the association between schizophrenia and polymorphism of the GSTM1 gene. DNA samples were obtained from 87 unrelated patients with schizophrenia who met the DSM-IV criteria for schizophrenia and from 176 control subjects. Individuals of both groups were ethnically Japanese and were from the same district. GSTM1 polymorphism was determined using the polymerase chain reaction method. The frequency of the GSTM1*0 allele was significantly higher amongst the patients with schizophrenia compared to controls (P = 0.0075). Moreover, the incidence of the GSTM1*0 was significantly higher amongst the schizophrenic patients classified as disorganized type (P = 0.0008), relative to the control sample. Our findings suggest that the GSTM1*0 is associated with an increased susceptibility to schizophrenia, particularly disorganized type of the disease. It is therefore likely that the GSTM1 gene deletion constitutes to vulnerability for disease states of this kind, rather than being the direct cause of schizophrenic conditions.

Adult↗

PubMed2001

Effects of high ELF magnetic fields on enzyme-catalyzed DNA and RNA synthesis in vitro and on a cell-free DNA mismatch repair.

Environmental electromagnetic fields have been implicated in human cancers. We examined whether high extremely low frequency (ELF) AC magnetic fields could affect DNA synthesis, transcription or repair, using in vitro model systems with defined sequences. The rate and fidelity of DNA polymerase catalyzed DNA synthesis, as well as of RNA polymerase catalyzed RNA synthesis, were not statistically significantly affected by 60 Hz 0.25-0.5 Tesla magnetic fields. The efficiency of mutS dependent mismatch repair with human cell extracts was also not affected by the magnetic field exposure. The results suggest that the core processes related to the transmission of genetic information are stable under high ELF magnetic fields.

Animals↗

PubMed2001

Exposure of Caenorhabditis elegans to extremely low frequency high magnetic fields induces stress responses.

Responses of the small heat shock protein gene, hsp-16, were examined in transgenic Caenorhabditis elegans exposed to electromagnetic fields. Expression of the hsp-16-lacZ gene was enhanced when transgenic animals were exposed to magnetic fields up to 0.5 T at 60 Hz. The hsp-16 promoter was more efficiently expressed at the embryonic than at the post-embryonic stage irrespective of exposure. Promoter activity was more sensitive to the stimulus in the intestine at the post-embryonic stage. Evidence is presented that the induction occurs at the transcriptional step of hsp-16.

Animals↗

PubMed2001

Improvement of splenomegaly and pancytopenia by enzyme replacement therapy against type 1 Gaucher disease: a report of sibling cases.

Gaucher disease is a genetic lipid storage disease and represents a potentially serious health problem. It arises from a deficiency of glucocerebrosidase activity with secondary accumulation of large quantities of glucocerebroside. Symptoms are usually multisystemic, often debilitating or disabling, and sometimes disfiguring, and they can lead to death. We report objective clinical response's to repeated infusion of human placental and recombinant glucocerebrosidase in 2 patients with type 1 Gaucher disease and increased hemoglobin levels and platelet counts. Splenic volume decreased during the period of enzyme administration. Enzyme replacement therapy has improved the treatment of type 1 Gaucher disease by safely and effectively arresting, decreasing, or normalizing many of its major signs and symptoms. Consideration by physicians must be given to Gaucher disease, and appropriate treatments must be given when confronted with cryptogenic pancytopenia or hepatosplenomegaly.

Adult↗

PubMed2001

Differential in vitro effects of IL-4, IL-10, and IL-13 on proinflammatory cytokine production and fibroblast proliferation in rheumatoid synovium.

The purpose of this study was to compare the potential of interleukin-4 (IL-4), IL-10, and IL-13 to interrupt two major inflammatory pathways in rheumatoid arthritis (RA), i.e., overexpression of proinflammatory cytokines and cytokine-mediated fibroblast growth. IL-4, IL-10, and IL-13 were all able to significantly inhibit the production of IL-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 by freshly isolated RA synovial tissue cells, IL-10 was most effective in terms of IL-1beta and TNF-alpha reduction. The IL-1 receptor antagonist was enhanced by IL-4 and IL-13, but only slightly enhanced by IL-10. Spontaneous interferon-gamma secretion was diminished by IL-4 and IL-10 but not by IL-13. Addition of anti-IL-10 neutralizing antibody to RA synovial tissue cells resulted in a substantial increase in IL-1beta and TNF-alpha levels, whereas neither anti-IL-4 nor anti-IL-13 antibody had a significant effect. IL-1beta-stimulated proliferation of RA synovial fibroblast cell lines was inhibited by IL-4 and IL-13, but not by IL-10; IL-4 was over tenfold more effective than IL-13. These results suggest that IL-4, IL-10, and IL-13 all have the therapeutic potential to regulate the disease activity mediated by proinflammatory cytokines in RA, but each cytokine may have different potencies.

Arthritis, Rheumatoid↗

PubMed2001

Association analysis of polymorphisms in the prepronociceptin gene and schizophrenia.

The human prepronociceptin (ppNoc) gene is located on chromosome 8p21, and several linkage studies have suggested that the susceptibility locus for schizophrenia is present in this chromosomal region. We investigated genetic variations in the promoter and coding regions of the ppNoc gene to determine if there may be an association between naturally occurring mutations and the manifestation of schizophrenia. Association analyses for the variations found were conducted between 87 unrelated schizophrenic patients and 100 healthy controls. Polymorphisms were found at both the -503 locus (G/A) in the promoter region and the 353 locus (Ala118Gly) in exon 3. Additionally, rare variants were identified at the -261 locus (A/G) in the promoter region, the 515 locus (Gln172Arg) in exon 3, and the 561 locus (G/A) in the untranslated region of exon 3. A significant difference was observed in allele frequency at the 353 locus between controls and patients with continuous-course schizophrenia (P = 0.0237), and between patients with and without prominent negative symptoms (P = 0.0201). However, neither difference was significant after Bonferroni correction. In addition, there were no significant differences in genotype and allele frequencies at either the -503 or 353 locus between the control group and patients with schizophrenia. These results suggest that ppNoc gene polymorphisms have no association with schizophrenia.

Adult↗

PubMed2001

Different expression of androgen receptor coactivators in human prostate.

OBJECTIVES: To investigate the expression of androgen receptor (AR) coactivators in the human prostate for a better understanding of androgen action in prostate cancer. METHODS: Using reverse transcriptase-polymerase chain reaction, we examined the expression levels of AR coactivators (ARA55, SRC1, ARA54, TIF2, RAC3) in four prostate cancer cell lines (DU145, PC3, LNCaP, and LN-TR2), nine benign prostatic tissue samples, and 21 prostate cancer tissue specimens. RESULTS: In the cell lines, SRC1 was expressed ubiquitously at almost equal amounts. Contrary to this, ARA55, ARA54, TIF2, and RAC3 displayed cell line-specific expression. In the LN-TR2 cells, established from LNCaP cells by long-term treatment with tumor necrosis factor-alpha, the expression levels of ARA55 and TIF2 were much higher than those in the LNCaP cells. In every prostatic tissue specimen, the expression levels of TIF2 and RAC3 were very low. The expression levels of ARA55 and SRC1 were higher in the cancer specimens with a higher grade or poor response to endocrine therapy than in those with a lower grade or good response to endocrine therapy. CONCLUSIONS: Prostate cancer cells express AR coactivators. Long-term stimulation by tumor necrosis factor-alpha could increase ARA55 and TIF2 expression in LNCaP cells. The different expression of coactivators may contribute to the different response of prostate cancer to androgenic stimulation or endocrine therapy.

Androgens↗

PubMed2001

Reduction of white coat effect by cilnidipine in essential hypertension.

Stress elevates blood pressure (BP) by increased sympathetic nerve activity. Cilnidipine, a novel dihydropyridine calcium antagonist that has inhibitory actions on N-type as well as L-type voltage-dependent calcium channels, has been reported to attenuate the cold stress-induced increase in plasma norepinephrine and BP in rats. Because white coat effect is associated with an enhanced pressor response to mental stress, we postulated that cilnidipine would attenuate white coat effect in patients with essential hypertension. Sixty-one consecutive outpatients (50 men, 11 women) with essential hypertension were studied prospectively. Twenty-nine patients were treated with either cilnidipine (n = 15) or nifedipine, a representative L-type voltage-dependent calcium antagonist (n = 14). Gender, age, body mass index, duration of hypertension, target organ damage of hypertension, and BP and heart rate (HR) were not significantly different between cilnidipine and nifedipine groups, and both systolic (SBP) and diastolic BP (DBP) were significantly decreased after treatment in both groups. White coat effects on systolic and DBP and HR were not significantly different between groups before antihypertensive treatment. Cilnidipine, but not nifedipine, significantly reduced white coat effects on SBP and HR. Furthermore, white coat effects on systolic BP and HR were significantly lower after treatment in the cilnidipine group compared with the nifedipine group. These data suggest that cilnidipine may reduce white coat effect in hypertensive patients by N-type calcium channel antagonism.

Blood Pressure↗

PubMed2001

Expression of the prostaglandin E(2) (PGE(2)) receptor subtype EP(4) and its regulation by PGE(2) in osteoblastic cell lines and adult rat bone tissue.

Prostaglandins E (especially PGE(2)) stimulate bone formation and increase bone mass in several species including man. The mechanism for this effect, the target cells, and the receptors involved are not known. Specific cell-surface receptors for PGE(2) (EP(1-4)) have been cloned and characterized. EP(4) was reported to be the major receptor in embryonic and neonatal bone tissue in mice, especially in preosteoblasts; however, no data are available regarding its expression in adult bone. This study examines the expression of EP(4) in bone tissue of young adult rats, in which PGE(2) is markedly anabolic, and in various osteoblastic cell lines. Using northern blot analysis, we found that osteoblastic cell lines RCT-1, RCT-3, TRAB-11, and RP-1, primary osteoblastic cells harvested from fetal rat calvaria, as well as tibiae and calvariae of 5-week-old rats express 3.8 kb EP(4) messenger RNA (mRNA). Treatment of periosteal cells (RP-1) in vitro with 10(-6) mol/L PGE(2) increased the levels of both EP(4) mRNA and EP(4) protein, peaking at 1-2 h. Similarly, systemic administration of an anabolic dose of PGE(2) (3-6 mg/kg) to young adult rats upregulated the expression of EP(4) in the tibia and calvaria, also peaking at 1-2 h. Using in situ hybridization, we found increased expression of EP(4) in bone marrow cells of the tibial metaphysis in response to systemic PGE(2) treatment. The preosteoblastic nature of these EP(4)-expressing cells was suggested by the fact that dexamethasone-treated bone marrow stromal cells in culture express EP(4) mRNA, which is upregulated by PGE(2). Northern blot analysis failed to detect both basal and PGE(2)-induced EP(2) mRNA in the bone samples or cell lines tested. Taken together, these data implicate EP(4) as the major cyclic AMP-related PGE(2) receptor subtype expressed in bone tissue and osteoblastic cells and indicate that this receptor is upregulated by its ligand, PGE(2).

Animals↗

PubMed2001

Human T-cell leukemia virus type-I (HTLV-I) tax is not the only one factor to enhance human immunodeficiency virus type-I (HIV-1) infection in culture-supernatants.

It is hypothesized that supernatants from cell cultures contain several factors to modify the human immunodeficiency virus type-1 (HIV-1) infection. Single round infection with pseudotyped viruses with envelope from HIV-1, amphotropic murine leukemia virus (A-MLV) and vesicular stomatitis virus G-protein (VSV-G) carrying luciferase reporter gene detected that not only human T-cell leukemia/lymphoma virus type-I (HTLV-1) transformed cells but also HTLV-I-unrelated T-cells and BJA-B cells released factors enhancing the infection with all pseudotyped viruses in their culture-supernatants. No supernatants upregulated the level of transcription from transfected DNA probe. suggesting that the action of supernatants is different from that of tumor necrosis factor (TNF) and Tax of HTLV-I. These results indicated that factors not always related to HTLV-I were ubiquitously produced and promoted viral infections, probably due to non-specific enhancement of early phase of the infection.

B-Lymphocytes↗

PubMed2001

Aspirin enhances the induction of type I allergic symptoms when combined with food and exercise in patients with food-dependent exercise-induced anaphylaxis.

We examined the effect of aspirin as a substitute for exercise in inducing urticaria/anaphylaxis in three patients with food-dependent exercise-induced anaphylaxis (FDEIA). Two of the patients had specific IgE antibodies to wheat and the other had antibodies to shrimp. Administration of aspirin before ingestion of food allergens induced urticaria in one patient and urticaria and hypotension in another, while aspirin alone or food alone elicited no response. The third patient developed urticaria only when he took all three items, i.e. aspirin, food and additional exercise, whereas provocation with any one or or two of these did not induce any symptoms. These findings suggest that aspirin upregulates type I allergic responses to food in patients with FDEIA, and further shows that aspirin synergizes with exercise to provoke symptoms of FDEIA. This is the first report of a synergistic effect of aspirin in inducing urticaria/anaphylaxis, which was confirmed using challenge tests in patients with FDEIA.

Adolescent↗

PubMed2001

Low-attenuation areas of the lungs on high-resolution computed tomography in asthma.

To investigate the low-attenuation areas of the lungs (LAA) in asthma, we compared the mean lung density (MLD) and the LAA in 22 asthmatics (12 ex-smokers and 10 nonsmokers) and 13 patients with chronic obstructive pulmonary disease (COPD) by high-resolution computed tomography. The MLD and the relative area of the lung with attenuation values lower than -950 Hounsfield Units at full inspiration (inspiratory RA950) were significantly different in nonsmoking asthmatics compared to patients with COPD and asthmatics with a smoking history. The MLD and the RA950 correlated significantly with the FEV1 in all groups and with the DL(CO) in patients with COPD and asthmatics with a smoking history but not in nonsmoking asthmatics. We concluded that the LAA in asthmatics with a smoking history indicates the presence of emphysema, but in nonsmoking asthmatics it reflects hyperinflation and nonemphysematous expiratory airflow limitation rather than emphysematous lesions.

Administration, Inhalation↗