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Biomedical subjects

Toshio Ishikawa

Publications and source records attributed to Toshio Ishikawa.

At least 19 recordsLinked to original sources
PubMed2006

Possible role of preproghrelin gene polymorphisms in susceptibility to bulimia nervosa.

Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty-six eating disorder patients, including 131 anorexia nervosa (AN)-restricting types (AN-R), 97 AN-binge eating/purging types (AN-BP) and 108 bulimia nervosa (BN)-purging types (BN-P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D' = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN-P (allele-wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72-3056C in BN-P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN-P.

Adult↗
PubMed2006

Gene expression signatures that can discriminate oral leukoplakia subtypes and squamous cell carcinoma.

The purpose of this study is to generate a classifier for oral squamous cell carcinoma (OSCC) and leukoplakias (LPs), and evaluate its diagnostic potential. In order to identify marker gene candidates, differential gene expression between LPs and OSCCs were examined by cDNA microarray. The expression of 118 marker gene candidates was further evaluated by quantitative reverse transcription-PCR (QRT-PCR) analyses of 27 OSCC and 19 LP tissues. We identified 12 up-regulated and 15 down-regulated marker genes in OSCCs compared to LPs. Using Fisher's linear discriminant analysis (LDA), we demonstrated that 11-gene predictors among this novel marker set could best distinguish OSCCs from LPs (>97% accuracy), whereas a further seven of these gene predictors could be utilized to distinguish higher grade (higher than moderate) from lower grade (lower than mild) dysplasias (>95% accuracy). These predictor gene sets provide multigene classifiers for the diagnosis of pre-cancerous to cancerous transition of oral malignancy.

Adult↗
PubMed2006

[Fluticasone propionate aqueous nasal spray for the treatment of chronic sinusitis with eosinophil].

Chronic sinusitis with eosinophils easily recurs after endoscopic sinus surgery. The condition is usually complicated by asthma, and many eosinophils are present in the sinus mucosa. One conservative treatment method is the administration of glucocorticoids locally or systematically. To evaluate the efficacy and tolerability of intranasal fluticasone propionate for the treatment of chronic sinusitis with eosinophils, seven patients with chronic sinusitis with eosinophils were treated over a 12-week period using a fluticasone propionate aqueous nasal spray (800 microg per day in each nostrilz). The Symptons of 7 patients, especially nasal discharge and nasal obstructions, improved and an expanded air space was observed on paranasal CT images. The percent of drug systemically available after intranasal administration varied by less than 1% for intranasal fluticasone propionate. Therefore, even if intranasal fluticasone propionate is administerved at double the usual dose, it is unlikely to cause systemic side effects. Fluticasone propionate aqueous nasal spray at double the usual dose is effective for the treatment of chronic sinusitis with eosinophils.

Administration, Intranasal↗
PubMed2006

High-fat diet in low-dose-streptozotocin-treated heminephrectomized rats induces all features of human type 2 diabetic nephropathy: a new rat model of diabetic nephropathy.

BACKGROUND AND AIM: We have developed a new rat model that mimics the natural course of diabetic nephropathy seen in type 2 diabetes. METHODS: Nine days after intravenous injection of streptozotocin (STZ) (40 mg/kg) or vehicle to 8-week-old male Sprague-Dawley rats, the animals' right kidneys were surgically removed. Two weeks after surgery, the STZ-injected rats were fed on either a high-fat (ST+HF) or a normal (ST) diet, while the vehicle-injected rats were fed on the high-fat diet (HF). RESULTS: Baseline biochemical markers did not differ between the three groups. Only the ST+HF group showed a significant increase in plasma glucose levels after 15 weeks, and simultaneously plasma insulin levels started to decrease, followed by an increase in plasma total cholesterol and triglyceride levels at 25 weeks and slightly later by an increase in blood pressure. In the ST+HF group, significant microalbuminuria was detected at 15 weeks followed by overt proteinuria, both of which were absent in the other two groups. Also in ST+HF, the creatinine clearance rate increased until week 15, and then gradually decreased. Histologically, ST+HF rats showed mesangial expansion at week 25, and diffuse glomerular sclerosis at the end of the experiments. CONCLUSION: The chronological changes in biochemical, physiological and histological markers in ST+HF rats are reminiscent of human type 2 diabetes and nephropathy. Our new model of type 2 diabetic nephropathy should help us to understand the pathophysiology of the disease and serve to explore measures to prevent and treat diabetic nephropathy.

Animals↗
PubMed2006

Development and validation of the psychosomatic scale for atopic dermatitis in adults.

Psychosocial factors play an important role in the course of adult atopic dermatitis (AD). Nevertheless, AD patients are rarely treated for their psychosomatic concerns. The purpose of the present study was to develop and validate a brief self-rating scale for adult AD in order to aid dermatologists in evaluating psychosocial factors during the course of AD. A preliminary scale assessing stress-induced exacerbation, the secondary psychosocial burden, and attitude toward treatment was developed and administered to 187 AD patients (82 male, 105 female, aged 28.4 +/- 7.8, 13-61). Severity of skin lesions and improvement with standard dermatological treatment were assessed by both the dermatologist and the participant. Measures of anxiety and depression were also determined. In addition, psychosomatic evaluations were made according to the Psychosomatic Diagnostic Criteria for AD. Factor analysis resulted in the development of a 12-item scale (The Psychosomatic Scale for Atopic Dermatitis; PSS-AD) consisting of three factors: (i) exacerbation triggered by stress; (ii) disturbances due to AD; and (iii) ineffective control. Internal consistency indicated by Cronbach's alpha coefficient was 0.86 for the entire measure, 0.82 for (i), 0.81 for (ii), and 0.77 for (iii), verifying the acceptable reliability of PSS-AD. Patients with psychosomatic problems had higher PSS-AD scores than those without. PSS-AD scores were positively associated with the severity of the skin lesions, anxiety and depression. The scores were negatively associated with improvement during dermatological treatments. In conclusion, PSS-AD is a simple and reliable measure of the psychosomatic pathology of adult AD patients. It may be useful in dermatological practice for screening patients who would benefit from psychological or psychiatric interventions.

Adolescent↗
PubMed2005

Aromatase-independent testosterone conversion into estrogenic steroids is inhibited by a 5 alpha-reductase inhibitor.

Estrogens are generated mainly by the action of aromatase, which converts testosterone to estradiol and androstenedione to estrone. However, in addition to estradiol and estrone, a variety of other steroids, whose synthesis is not dependent on aromatase, can stimulate the estrogen receptor. Here we show that testosterone is converted into such estrogenic steroids by aromatase-negative HeLa cells. This aromatase-independent generation of estrogenic steroids is seen in aromatase-positive MCF-7 cells as well. In both cell lines, the synthesis of estrogenic steroids was blocked by inhibition of testosterone conversion into dihydrotestosterone using a 5 alpha-reductase inhibitor finasteride, suggesting that they are generated downstream of dihydrotestosterone. This finding raises the possibility that the combination of a 5 alpha-reductase inhibitor and an aromatase inhibitor may reduce estrogenic steroids in vivo more completely than an aromatase inhibitor alone.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2005

ERE-independent ERalpha target genes differentially expressed in human breast tumors.

The classical pathway for estrogen receptor (ER) signaling is mediated by ER binding to an estrogen response element (ERE) in DNA. ERalpha can also act via a nonclassical pathway by altering the activities of other transcription factors (e.g., Sp1, AP-1, or NF-kappaB) at their cognate sites on DNA. We previously generated a mutant form of ERalpha (E207A/G208A) that does not bind to EREs, and therefore lacks signaling via the classical pathway but retains signaling via the nonclassical pathway. In the current study, we introduce this mutant ERalpha into MDA-MB231 ERalpha-negative breast carcinoma cells to identify nonclassical pathway genes that respond to 17beta-estradiol (E2), selective estrogen receptor modulators (SERMs) tamoxifen (TAM) or raloxifene (RAL), or the estrogen antagonist ICI 182,780 (ICI). Consistent with a role for nonclassical signaling in SERM action, microarray analyses identify 268 responsive nonclassical ERalpha pathway target genes. ICI elicits the largest number of nonclassical genes, followed by RAL, TAM, and E2. Custom microarrays containing identified nonclassical ERalpha responsive genes are used to compare gene expression in human breast tumor (n = 34) and normal mammary epithelial cell (n = 9) samples. A subset of nonclassical genes (n = 32) are differentially expressed in breast tumors. In summary, we show that nonclassical ERalpha pathway target genes exhibit a range of transcriptional responses to SERMs and identify targets of this pathway as potentially relevant to breast cancer. The identification of nonclassical ERalpha target genes offers new insight into estrogen receptor signaling and cross talk with pathways that mediate breast tumor response to SERM therapy.

Breast Neoplasms↗
PubMed2005

Association between perceived social support and Th1 dominance.

Social support is supposed to have a positive health effect via alteration of immunity. In this study, associations between perceived social support and immune systems were examined. Immunological assessments, e.g. T cell count, Natural Killer cell count, Interferon-gamma, Interleukin-4, and psychological assessments, e.g. Generic Job Stress Questionnaire were conducted on male employees. Two-way (social support x job stressor) analyses of covariance controlling for age, smoking, alcohol consumption, and exercise revealed that there were main effects of perceived social support on NK cell counts, IL-4, and Th1/Th2 balance. On the other hand, interaction effects were observed on T cell counts and INF-gamma production in vitro. Social support affects immune function in a way that is consistent with both the direct and buffering hypotheses depending on the sources of support and the immune parameter.

Adult↗
PubMed2005

[Systemic effects of intranasal steroid drops in patients with dysosmia].

PURPOSE: To evaluate the systemic effects of intranasal steroid drops in patients with dysosmia. CASES AND METHODS: Intranasal steroid drops were administered for 12 weeks to 23 patients with dysosmia, and their plasma cortisol and adrenocorticotropic hormone (ACTH) values were measured before and after treatment. Improvement in dysosmia was judged based on the standerd olfactory test and the patients' symptoms. RESULTS: The post-treatment plasma cortisol levels ranged from 0.1 to 25.0 microg/dl (5.4 +/- 5.9 microg/dl), and the posttreatment plasma ACTH levels ranged from 5.0 to 55.0 pg/ml (13.8 +/- 11.7 pg/ml). After treatment, the 23 cases were divided into two groups: 14 cases (60.9%) with a decline in cortisol and/or ACTH level, and 9 patients (39.1%) with normal plasma cortisol and ACTH levels. Improvement in dysosmia was found in 4 patients (28.6%) in the former group and 4 patients (44.4%) in the latter group. The difference in percentage of patients who improved was not significant between the groups. CONCLUSIONS: We conclude that the direct topical effect of intranasal steroid drops on the olfactory mucosa may have been the principal reason for the improvement in the patients' dysosmia.

Administration, Intranasal↗
PubMed2004

Uncoupling protein-2/uncoupling protein-3 gene polymorphism is not associated with anorexia nervosa.

Energy expenditure abnormalities have been observed in anorexia nervosa (AN). The uncoupling proteins (UCPs) have been implicated as having a role in energy metabolism and thermogenesis, and an association between a marker flanking the UCP-2/UCP-3 gene cluster and AN has been reported. Also known are insertion/deletion and -866G/A polymorphisms in the UCP-2 gene, and the -55C/T polymorphism in the UCP-3 gene. Differences in these alleles are reportedly related to changes in energy expenditure, body mass index, fat tissue accumulation and obesity. Therefore, this case-control association analysis was done to determine whether any of these UCP-2/3 gene polymorphisms are related to a predisposition to AN. In analysis of a cohort of 106 female Japanese AN sufferers and 126 normal female controls, we found no between-group differences in the polymorphism frequencies of these groups. The hypothesis that differences in the UCP-2/3 gene influence the susceptibility to AN was not supported.

Adult↗
PubMed2004

Nonhomologous end-joining ligation transfers DNA regulatory elements between cointroduced plasmids.

Cointroduction of plasmids into mammalian cells is commonly used to investigate transcription factor regulation of reporter genes or to normalize transfection efficiency. We report here that cotransfected DNA molecules commonly transfer enhancer elements from one plasmid to another. Using separate Renilla or Firefly luciferase reporters, we found that an estrogen response element (ERE) originally linked to one of the reporters stimulated expression of the non-ERE-containing reporter. Similar enhancer transfer was seen with the cytomegalovirus enhancer. This enhancer transfer effect was not seen when cells were transfected separately with the reporters and the extracts were then combined before luciferase assays. The degree of enhancer transfer increased with transfected plasmid concentration and was greater when linearized rather than circular plasmid DNA was used. We hypothesized that double-strand breaks and heteroligation of cointroduced DNA molecules mediated the transfer of regulatory elements from one molecule to another. PCR of transfected plasmid DNA confirmed nonhomologous end-joining (NHEJ) ligation of DNA fragments originally present in separate plasmids. The NHEJ reaction was enhanced by UV light treatment to introduce double-strand breaks, and it was greater after liposome-mediated transfection than after calcium-phosphate-mediated transfection. NHEJ also occurred after adenoviral transfer of DNA into cells. We conclude that NHEJ mediates the transfer of regulatory DNA elements among cointroduced DNA molecules. These findings indicate the need for caution when interpreting results of transfection experiments containing more than one plasmid and suggest a mechanism whereby viruses or other exogenous DNA might recombine to activate unrelated genes.

Adenoviridae↗
PubMed2002

Cysteine protease activity and histamine release from the human mast cell line HMC-1 stimulated by recombinant streptococcal pyrogenic exotoxin B/streptococcal cysteine protease.

We constructed the expression vector pSK-SCP containing the streptococcal exotoxin B gene (spe b) which expressed protease activity. We showed that the recombinant streptococcal pyogenic exotoxin B/streptococcal cysteine protease (rSPE B/SCP) was secreted into the culture supernatant of the transformant and retained its SCP activity, which was equivalent to or greater than that of the naturally occurring molecule. The secreted rSPE B/SCP induced histamine release and degranulation of the human mast cell line HMC-1. This study may contribute to the understanding of the pathogenic role of SPE B/SCP in streptococcal infection and streptococcal toxic shock syndrome.

Bacterial Proteins↗
PubMed2002

An estrogen receptor (ER)alpha deoxyribonucleic acid-binding domain knock-in mutation provides evidence for nonclassical ER pathway signaling in vivo.

We created a nonclassical estrogen receptor (ER) knock-in mouse model by introducing a mutation that selectively eliminates classical ER signaling through estrogen response elements, while preserving the nonclassical ER pathway. Heterozygous nonclassical ER knock-in (NERKI) females are infertile. Their ovaries contain no corpora lutea, reflecting a defect in ovulation, and the stromal cells contain lipid droplets, suggesting altered steroidogenesis. The uteri are enlarged with evidence of cystic endometrial hyperplasia, and the mammary glands are hypoplastic. These phenotypic features indicate differential ER effects on growth and development in various estrogen-responsive tissues. These findings suggest that nonclassical ER signaling pathways play an important physiological role in the development and function of the reproductive system.

Animals↗