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Biomedical subjects

M Igawa

Publications and source records attributed to M Igawa.

At least 19 recordsLinked to original sources
PubMed1998

Dietary carbohydrates enhance lactase/phlorizin hydrolase gene expression at a transcription level in rat jejunum.

We have previously shown that dietary sucrose stimulates the lactase/phlorizin hydrolase (LPH) mRNA accumulation along with a rise in lactase activity in rat jejunum [Goda, Yasutake, Suzuki, Takase and Koldovský (1995) Am. J. Physiol. 268, G1066-G1073]. To elucidate the mechanisms whereby dietary carbohydrates enhance the LPH mRNA expression, 7-week-old rats that had been fed a low-carbohydrate diet (5.5% of energy as starch) were given diets containing various monosaccharides or sucrose for 12h. Among carbohydrates examined, fructose, sucrose, galactose and glycerol elicited an increase in LPH mRNA accumulation along with a rise in lactase activity in the jejunum. By contrast, glucose and alpha-methylglucoside were unable to elicit a significant increase in LPH mRNA levels. To explore a transcriptional mechanism for the carbohydrate-induced increases in LPH mRNA levels, we employed two techniques currently available to estimate transcriptional rate, i.e. RNA protection assays of pre-mRNA using an intron probe, and nuclear run-on assays. Both assays revealed that fructose elicited an increase in transcription of the LPH gene, and that the transcription of LPH was influenced only slightly, if at all, by glucose intake. These results suggest that certain monosaccharides such as fructose or their metabolite(s) are capable of enhancing LPH mRNA levels in the small intestine, and that transcriptional control might play a major role in the carbohydrate-induced increase of LPH mRNA expression.

Animals↗
PubMed1998

Comparison of chromosomal aberrations detected by fluorescence in situ hybridization with clinical parameters, DNA ploidy and Ki 67 expression in renal cell carcinoma.

To evaluate the significance of chromosomal aberrations in renal cell carcinoma, fluorescence in situ hybridization (FISH) was used to determine its prevalence and correlation with clinical parameters of malignancy. In addition, correlation of chromosomal aberration with Ki 67 expression was analysed. We performed FISH with chromosome-specific DNA probes, and the signal number of pericentromeric sequences on chromosomes 3, 7, 9 and 17 was detected within interphase nuclei in touch preparations from tumour specimen. The incidence of loss of chromosome 3 was significantly higher than those of chromosomes 7, 9 and 17 (P < 0.001, P = 0.03 and P < 0.001 respectively). Hyperdiploid aberration of chromosomes 3 and 17 was significantly correlated with tumour stage (P = 0.03, P = 0.02 respectively), whereas hyperdiploid aberration of chromosome 9 was associated with nuclear grade (P = 0.04). Disomy of chromosome 7 was correlated with venous involvement (P = 0.04). Ki 67 expression was significantly associated with hyperdiploid aberration of chromosome 17 (P = 0.01), but not with aberration of chromosome 3. There was a significant relationship between hyperdiploid aberration of chromosome 7 and Ki 67 expression (P = 0.01). In conclusions, gain of chromosome 17 may reflect tumour development, and aberration of chromosome 7 may affect metastatic potential of malignancy, whereas loss of chromosome 3 may be associated with early stage of tumour development in renal cell carcinoma.

Adult↗
PubMed1998

Heat-induced membrane damage combined with adriamycin on prostate carcinoma PC-3 cells: correlation of cytotoxicity, permeability and P-glycoprotein or metallothionein expression.

OBJECTIVE: To assess heat-induced membrane damage in a prostate cancer cell line when combined with adriamycin treatment. MATERIALS AND METHODS: The changes in intracellular adriamycin accumulation, cell proliferation and cell-cycle fractions were examined after human prostate carcinoma PC-3 cells were exposed to heat and/or further treatment with adriamycin. Proliferation and the cell cycle were determined using adherent cell analysis and sorting laser cytometry (ACAS) or flow cytometry. P-glycoprotein (PGP) and metallothionein (MT) expression, which may have a physiological role in the transport of or reduction in cytotoxicity of some anticancer drugs, were also analysed after cells were exposed to heat, using immunohistochemical or flow cytometric methods. RESULTS: There was a significant increase in intracellular adriamycin accumulation, related to both influx (P<0.05) and efflux (P<0.01), in cells treated with adriamycin, especially after heating them at 44 degrees C for 1 h. There was a significant decrease in cell proliferation of preheated cells when exposed to adriamycin, especially at 44 degrees C (P<0.05). In the cell-cycle analysis, cells preheated at 44 degrees C showed partial accumulation in the debris or apoptotic fraction at 24 h, and many cells accumulated in these fractions at 48 h. There was significantly less PGP or MT expression in cells preheated at 44 degrees C than in control cells or cells preheated at 41 degrees C (P<0.01). This reduction in PGP or MT level by heating may inhibit drug efflux and thus increase intracellular drug level at elevated temperatures. CONCLUSIONS: These results suggest that hyperthermia may damage the drug-exclusion mechanism in these cells and thus increase the effectiveness of drug action.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Cerebral blood volume in the sleep measured by near-infrared spectroscopy.

We investigated the relationship between hemodynamic changes in the cortex measured by near-infrared spectroscopy (NIRS) and the polysomnographic changes during sleep. Four healthy male volunteers participated in the study. Near-infrared spectroscopy measuring and polysomnographic recordings were done simultaneously during sleep. In many case, oxy-hemoglobin (oxy-Hb) decreased and deoxy-hemoglobin (deoxy-Hb) increased during the transition from wakefulness to sleep, and oxy-Hb increased toward deep sleep. Oxy-Hb and deoxy-Hb had larger fluctuations during REM sleep than those during non-REM sleep. During REM sleep, oxy-Hb often showed a lower level and deoxy-Hb showed a higher level than those during the preceding and following non-REM sleep.

Adult↗
PubMed1998

Catheter ablation of ventricular tachycardia in patients with right ventricular dysplasia: Identification of target sites by entrainment mapping techniques.

OBJECTIVE: To identify target sites for radiofrequency ablation of ventricular tachycardia (VT) by entrainment mapping techniques in patients with arrhythmogenic right ventricular dysplasia. METHODS: Entrainment mapping and radiofrequency ablation of eight VTs was performed in seven patients. Radiofrequency ablation was applied at 31 reentry circuits sites that were classified based on findings during entrainment. RESULTS: By entrainment criteria the 31 sites were classified as: exit sites (n = 12), proximal sites (n = 6), and outer loop sites (n = 13). Radiofrequency current application terminated VT at 7 of 31 sites: 2 of 12 exit sites (17%), 4 of 6 proximal sites (67%), and 1 of 13 outer loop sites (8%). CONCLUSION: Radiofrequency ablation terminated VTs most often at sites proximal to the exit as opposed to outer loop sites and exit sites (P = 0.05). The critical isthmus for ablation of VT in right ventricular dysplasia often may be distant to the exit.

Arrhythmogenic Right Ventricular Dysplasia↗
PubMed1997

Overexpression of members of the AP-1 transcriptional factor family from an early stage of renal carcinogenesis and inhibition of cell growth by AP-1 gene antisense oligonucleotides in the Tsc2 gene mutant (Eker) rat model.

We previously isolated subtracted cDNA clones for genes having increased expression in Tsc2 gene mutant (Eker) rat renal carcinomas (RCs). Among them, fra-1 encoding a transcriptional factor activator protein 1 (AP-1) was identified. We have therefore investigated whether other members of the AP-1 transcription factor family might also be involved in renal carcinogenesis in the Eker rat model. In the present study, overexpression of fra-1, fra-2, c-jun, junB, and junD mRNAs was demonstrated in RCs by Northern blot analysis. Interestingly, AP-1 proteins were highly expressed even in the earliest preneoplastic lesions (e.g., phenotypically altered tubules) as suggested by immunohistochemistry. Moreover, 12-O-tetradecanoylphorbol-13-acetate-responsive element (TRE)-binding activity of AP-1 proteins was observed in RC cell extracts by electrophoretic mobility shift assay. As a next step, we transfected antisense oligonucleotides targeting AP-1 genes into RC cells and demonstrated that their growth was strongly inhibited. Thus, the data suggest that overexpression of AP-1 genes might play a crucial role in renal carcinogenesis in the Eker rat model.

Animals↗
PubMed1997

Immunohistochemical analysis of estramustine binding protein with particular reference to proliferative activity in human prostatic carcinoma.

BACKGROUND: The estramustine binding protein (EMBP) specifically binds to estramustine and was first discovered in the rat ventral prostate. However, the physiological property of EMBP in the human prostate still remains to be elucidated. To elucidate whether EMBP is interrelated with cellular proliferation in human prostatic carcinoma (PC), the change in EMBP immunostaining during luteinizing hormone-releasing hormone (LH-RH) analog administration or during Cis-platinum-based chemotherapy, and the difference in EMBP immunostaining between hormone refractory (hr-PC) and untreated PC were analyzed. METHODS: Forty-six patients with histologically proven untreated PCs (34 were treated with LH-RH analog and 12 were treated with chemotherapy as an initial therapy) and 14 with hr-PC were used in this study. PC tissues were obtained before and 3 months after the initial therapy. The changes in immunostainings for EMBP, proliferating cell nuclear antigen (PCNA), and nm23 protein were compared with the change in serum prostate-specific antigen (PSA) level and the histological response during the treatment. RESULTS: The increased EMBP expression was observed in tumors with high histological grade and high clinical stage as well as in hr-PC. In untreated PC, EMBP expression weakly correlated with PCNA or nm23 protein immunoreactivity. In PC receiving LH-RH analog, EMBP expression was significantly reduced after treatment, however, no significant changes were observed in PCNA or nm23 protein immunoreactivity. In addition, EMBP expression before the treatment significantly correlated with the serum PSA change, while PCNA expression and nm23 protein immunoreactivity did not. On the other hand, no significant relationship was observed between histological changes induced by the LH-RH analog and immunostainings for EMBP, PCNA, and nm23 protein before treatment. In PC patients receiving chemotherapy, immunostainings for EMBP, PCNA, and nm23 protein were not significantly changed during the treatment. EMBP immunoreactivity was significantly higher in hr-PC than in untreated PC with paralleled change of PCNA expression and nm23 protein immunoreactivity. CONCLUSIONS: These observations indicate that EMBP is androgen regulated in some PCs. However, EMBP expression is demonstrated even in hr-PC and is interrelated with cellular proliferation especially in hr-PC.

Aged↗
PubMed1997

Urethral caruncle with coexistence of intestinal heterotopia. A case report.

Urethral caruncle is one of the benign disorders which occurs frequently after the menopause. We describe a case of urethral caruncle with intestinal heterotopia, in which infiltration by lymphocytes, invagination of the urethral transitional epithelium causing nest formation, lumen formation, hypervascularity as well as teleangiectasia were observed, suggesting the occurrence of metaplasia in the transitional epithelium preceding the intestinal heterotopia. The aetiology and clinical significance of urethral caruncle exhibiting intestinal heterotopia are discussed.

Epithelium↗
PubMed1997

Inverted papilloma of the urinary bladder: a case evaluated for malignant potential.

We report a case of inverted papilloma in the urinary bladder with special reference to its malignant potential. A 77-year-old male patient complaining of microhaematuria was subjected to cystoscopic examination, which showed a non-papillary pedunculated tumour at the postero-lateral wall, and was treated with transurethral resection. The histological findings of the specimen were compatible with inverted papilloma of the urinary bladder, except for the presence of low grade dysplastic changes in the tumour nuclei. We revealed the malignant potential of this tumour, analyzing and evaluating nuclear DNA content, proliferating cell nuclear antigen (PCNA) as well as p53 expression.

Aged↗
PubMed1997

Chromosome aberrations in renal tumors detected by fluorescence in situ hybridization.

The aim of this study was to investigate the relationship between chromosome aberrations detected by fluorescence in situ hybridization (FISH) and tumor grade, stage, venous involvement, and DNA ploidy status in 18 renal tumors. Using FISH with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 3, 7, 9, and 17 was detected within interphase nuclei in touch preparations from tumor specimens. Monosomy for chromosome 3 was detected in seven of 9 DNA diploid tumors, whereas all DNA aneuploid tumors demonstrated trisomy or tetrasomy for chromosome 7. Moreover, monosomy for chromosome 3 was more frequently shown in the diploid and low-stage tumors than in the aneuploid and high-stage tumors. The percentage of hyperdiploid cells significantly correlated with DNA ploidy status in the case of chromosomes 3 and 7 (p = 0.030, p = 0.007, respectively). The percentage of hyperdiploid cells for chromosome 3 had borderline significance with tumor stage. On the other hand, the percentage of diploid cells for chromosome 17 was significantly correlated with DNA ploidy status and tumor stage (p = 0.030, p = 0.027, respectively). Moreover, the percentage of diploid cells for chromosome 7 in renal cell carcinoma (RCC) with venous involvement was significantly lower than those without venous involvement (p = 0.023). These results suggest that the incidence of chromosomal aberrations detected by FISH is more frequent than the chromosomal aneuploidy reported previously by conventional cytogenetics. Therefore, loss of chromosome 3 may be associated with an early event in RCC carcinogenesis. Gain of chromosomes 3 and 7 is correlated with tumor progression as well as gain and loss of chromosome 17. Study of the chromosomal aberrations may provide a greater understanding of tumor carcinogenesis and progression in RCC.

Adult↗
PubMed1997

Somatic mutation of the tuberous sclerosis (Tsc2) tumor suppressor gene in chemically induced rat renal carcinoma cell.

PURPOSE: von Hippel-Lindau (VHL) gene mutations are detected in noninherited, sporadic human renal cell carcinomas (RCs) at a high frequency. We recently identified a germline mutation in the rat homologue of the human tuberous sclerosis (TSC2) predisposing RC gene in the Eker rat model, and in this study we searched for mutations of the Tsc2 gene in chemically induced non-Eker rat RCs. MATERIALS AND METHODS: Chemically [N-ethyl-N-hydroxyethylnitrosamine (EHEN)]-induced non-Eker rat RC lines (designated as BP13 and BP36B) were subjected to PCR-single strand conformation polymorphism (PCR-SSCP) analysis using specific primers covering entire exons of Tsc2 gene (41 coding exons and one non-coding exon). We simultaneously searched for mutations of Vhl gene, a rat homologue of von Hippel-Lindau disease gene (VHL) as well as Tsc2 gene. RESULTS: BP36B showed an abnormal mobility shift from the normal tissue of the same rat in exon 35 on analysis by PCR-SSCP. This mutation was confirmed by direct sequencing and found to be a T-to-C transition at the second position of codon 1470, resulting in an amino acid change from leucine to proline (missense mutation). CONCLUSIONS: This is the first demonstration of Tsc2 gene somatic mutation in non-Eker rat RCs. Our present findings call attention to further investigation of the role of Tsc2 gene mutations in rat renal carcinogenesis and possible Tsc2 gene mutations in human RCs, especially of the non-clear cell type, which are not related to the VHL gene.

Animals↗
PubMed1997

Clinical significance of immunohistochemically detectable p53 protein in renal cell carcinoma.

OBJECTIVE: To elucidate the clinical significance of p53 protein in renal cell carcinoma (RCC). MATERIALS AND METHODS: The p53 protein in the paraffin-embedded materials taken from 72 patients with RCCs was evaluated immunohistochemically and was compared with the histological findings, expression of proliferating cell nuclear antigen (PCNA), genetic instability as assessed by 2c deviation index (2cDI) and 5c exceeding rate (5cER) as well as clinical outcome. RESULTS: The p53 positivity was demonstrated only in a localized and/or focal area of the cancerous tissue. The positive rate of p53 protein was 40.3% in this study. The p53 protein significantly correlated with nuclear grade as well as PCNA expression (p < 0.001 and p < 0.01, respectively). Although there was a wide scatter of 2cDI and 5cER values between p53 positive and negative RCCs, the RCC with positive p53 exhibited significantly higher values in 2cDI as well as 5cER, as compared to that with negative p53 (p < 0.02 and p < 0.005, respectively). However, some of the RCCs with negative p53 showed relatively higher values in 2cDI and 5cER. Using univariate analysis, the prognostic relevance was noted in T, N, M categories, age and p53 positivity, while it was not in 2cDI, 5cER and PCNA expression. Multivariate analysis demonstrated that N category and p53 positivity were independently significant indicators in predicting survival. CONCLUSIONS: The presence of p53 protein might reflect the genetic instability already occurred. The p53 positivity reflecting a high cellular proliferation could afford an additional but useful information when predicting survival in patients with RCC.

Carcinoma, Renal Cell↗
PubMed1997

Quantitative analysis of NM23 protein immunoreactivity in renal cell carcinoma using an image analyzer.

PURPOSE: nm23 is a candidate tumor suppressor gene. Whether or not tumor metastasis suppressive activity is present in renal cell carcinoma (RCC) was studied. MATERIALS AND METHODS: Immunohistochemical analysis of nm23 protein using an anti-human nm23 H1/H2 polyclonal antibody was performed in 67 RCCs and in the corresponding 67 normal proximal renal tubules (NTs). The quantity and intensity of nm23 protein immunoreactivity were evaluated using a computer-interfaced image analyzer, and the obtained results were compared with pathological findings and clinical outcome. RESULTS: The quantity and intensity of nm23 protein immunoreactivity were significantly higher in RCCs than those observed in NTs (p <0.0001, respectively). Both quantity and intensity of nm23 protein immunoreactivity held a tendency to increase along with histological grade (p = 0.094 and p = 0.089, respectively) and T category (p = 0.063 and p = 0.063, respectively). Similarly, the immunoreactivity had a tendency to be higher in RCCs with lymph node involvement than those tumors without involvement (p = 0.060 and p = 0.067, respectively). However, no significant difference in nm23 protein immunoreactivity was found between tumors with and without distant metastasis. Using a univariate analysis, a high nm23 protein immunoreactivity (quantity > or = 51.0% or intensity > or = 72.5%) significantly correlated with a poor clinical outcome (p = 0.0051 and p = 0.0013, respectively). Furthermore, a multivariate analysis adjusted to age, T, N and M categories, showed that a high intensity of nm23 protein immunoreactivity was significantly associated with a poor clinical outcome in patients with RCCs (p = 0.0192). CONCLUSIONS: Immunohistochemical analysis of nm23 protein intensity is an additional tool for analyzing the difference of biological features in RCCs. The potential role of the tumor metastasis suppressive activity of nm23 remains unclear in RCCs.

Adult↗
PubMed1997

[Androgen--biosynthesis, receptor and action].

Androgens play a key role in promoting normal sex differentiation and development, pubertal masculinization, initiation of spermatogenesis, and maintenance of male sexual function. In addition to these classical function, androgens are significantly associated with cell differentiation, proliferation as well as carcinogenesis. The function of androgens can be mediated by the androgen receptor (AR), which transduces the steroid signal within cells. AR belongs to the superfamily of nuclear receptors that employ complex genetic mechanisms to control the development and physiological functions of target tissues. AR activates or represses gene transcription through association with specific DNA elements and/or proteins. Moreover, molecular investigations of AR gene structure have provided new insights towards defining a genetic basis for the relationship between the diseased conditions and androgen action. Recent data on androgen biosynthesis, action of androgens and molecular genetic analysis of gene structure have led to a new understanding of the pathology in affected men. This review summarizes briefly our current view of androgen action with a special emphasis on the alterations of AR.

Androgen-Insensitivity Syndrome↗
PubMed1997

[Cryptorchidism].

Cryptorchidism represents the most common genital abnormalities in boys. Cryptorchidism means the abnormalities that lead to the empty scrotum and specifically refers to undescended testis. Testicular descent is multifactorial, and abnormalities of morphogenesis and hormonal aspects are considered to be the etiology of non-descent of the testis. Furthermore, hormonal abnormalities associated with cryptorchidism have the potential risks of infertility and malignancy that appear in later life. The modality of the management has undergone major refinements with the introduction of laparoscopy. Laparoscopy has become the most widely used and most useful diagnostic modality in the management of the impalpable undescended testes.

Child↗
PubMed1996

Immunohistochemical analysis of proliferating cell nuclear antigen, p53 protein and nm23 protein, and nuclear DNA content in transitional cell carcinoma of the bladder.

BACKGROUND: Transitional cell carcinoma (TCC) of the bladder displays an unpredictable biologic behavior and the morphologic methods of grading tumor malignancy are often insufficient to predict the clinical outcome of patients with TCC of the bladder. Thus, the new indicator should reliably reflect prognosis. In this study, the authors determined the prognostic significance of proliferating cell nuclear antigen (PCNA), p53 protein, and nm23 protein, as well as nuclear DNA content in specimens with TCC of the bladder. METHODS: Paraffin embedded materials taken from 77 patients with nonmetastatic untreated TCC of the bladder (classified as pTa-3b, NO, MO) treated with total cystectomy were employed in this study. PCNA expression, p53 protein and nm23 protein immunoreactivities, and the parameters for nuclear DNA content such as 2c deviation index (2cDI) and 5c exceeding rate (5cER) were evaluated using a computer-assisted image analyzer, and the results were compared with histologic findings and clinical outcome. RESULTS: PCNA expression positively correlated with p53 protein and nm23 protein immunoreactivities, 2cDI value, and 5cER. In addition, histologic grade positively correlated with all of these five parameters. Similarly, pT category and disease progression positively correlated with all of the five parameters, except for nm23 protein immunoreactivity. In tumors with high genetic instability as judged by 2cDI and 5cER, both PCNA expression and p53 protein immunoreactivity were elevated, whereas nm23 protein immunoreactivity was not. However, the percent coefficient of variation in PCNA expression was smaller than that observed in p53 protein immunoreactivity in each group of genetic instabilities. In univariate analysis, prognostic potential was found with histologic grade, pT category, PCNA expression, p53 protein immunoreactivity, 2cDI value, and 5cER, but was not noted in nm23 protein immunoreactivity. Multivariate analysis indicated that quantity and intensity of PCNA expression (chi 2 = 8; P = 0.0047 for quantity and chi 2 = 8.71; P = 0.0032 for intensity) and 2cDI value (chi 2 = 5.52; P = 0.0019) were independent variables of histologic grade and pT category when predicting survival. However, p53 protein and nm23 protein immunoreactivities and 5cER were not of independent significance. CONCLUSIONS: The tumor growth fraction as assessed by PCNA immunostaining is an independently significant predictor for survival of patients with TCC of the bladder.

Adult↗
PubMed1996

Clinical study on estramustine binding protein (EMBP) in human prostate.

To elucidate the characteristics of estramustine binding protein (EMBP) in human prostate, tissue EMBP concentration was examined in 42 benign prostatic hypertrophy (BPH), 34 untreated prostatic carcinoma (PC), 8 hormone refractory PC (hr-PC), as well as 13 control prostate human tissue samples by RIA using rat-EMBP antibody, and the concentration thus obtained was compared with dihydrotestosterone (DHT), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), and zinc, indices exhibiting androgen dependency in the prostate. EMBP concentration correlated significantly with DHT and PSA levels in the control prostate and BPH, but not in untreated PC. In BPH, EMBP concentration increased significantly after administration of fluoxymesterone (4 mg/day for 2 weeks), whereas it decreased significantly after estramustine phosphate (280 mg/day for 2 weeks). The EMBP/DHT ratio in moderately and poorly differentiated, and the hr-PC was significantly higher than in controls, BPH, and well-differentiated PC. In addition, untreated PC with an EMBP/DHT ratio of more than 40 showed significantly lower progression-free probability as compared with PC with an EMBP/DHT of less than 40. These results suggest that (1) EMBP in BPH and well-differentiated PC preserves androgen dependency, but not in moderately and poorly differentiated, nor in hr-PCs, indicating that EMBP is a protein different from PAP and PSA, and (2) that the tissue EMBP/DHT ratio might be useful as a marker for predicting disease progression.

Acid Phosphatase↗