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Biomedical subjects

M Murai

Publications and source records attributed to M Murai.

At least 19 recordsLinked to original sources
PubMed2001

Early postnatal ataxia and abnormal cerebellar development in mice lacking Xeroderma pigmentosum Group A and Cockayne syndrome Group B DNA repair genes.

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are rare autosomal recessive disorders associated with a defect in the nucleotide excision repair (NER) pathway required for the removal of DNA damage induced by UV light and distorting chemical adducts. Although progressive neurological dysfunction is one of the hallmarks of CS and of some groups of XP patients, the causative mechanisms are largely unknown. Here we show that mice lacking both the XPA (XP-group A) and CSB (CS-group B) genes in contrast to the single mutants display severe growth retardation, ataxia, and motor dysfunction during early postnatal development. Their cerebella are hypoplastic and showed impaired foliation and stunted Purkinje cell dendrites. Reduced neurogenesis and increased apoptotic cell death occur in the cerebellar external granular layer. These findings suggest that XPA and CSB have additive roles in the mouse nervous system and support a crucial role for these genes in normal brain development.

Animals↗
PubMed2001

A new recombinant human bone morphogenetic protein-2 carrier for bone regeneration.

A gelatin sponge was formed by foaming and heat treating a gelatin solution, followed by coating the solid with poly(D,L-lactic-co-glycolic acid) to reinforce the gelatin framework. This sponge was tested for its suitability as a biodegradable porous, recombinant human bone morphogenetic protein (rhBMP)-2 carrier. Incorporation of rhBMP-2 into the sponge was closely related to its bulk density of gelatin sponge. The calcium content in the sponges, as assessed by an ectopic bone formation assay in rats, increased with the increasing sponge bulk density. Histologic and peripheral quantitative computed tomography analysis of implants in this ectopic assay system revealed cell growth throughout the carrier in 4 weeks after implantation regardless gelatin bulk density. The carrier containing rhBMP-2 maintained its three-dimensional structure after implantation; the carrier resisted collapse caused by soft tissue pressure during rapid bone formation as assessed by soft X-ray photographs. These results indicate that this newly developed sponge has excellent carrier characteristics to introduce rhBMP-2 into areas needed for bone regeneration.

Animals↗
PubMed2001

Constitutive activation of nuclear factor-kappaB prevents TRAIL-induced apoptosis in renal cancer cells.

TRAIL has gained much attention for its specific induction of apoptosis in cancer cells but not in normal cells. This phenomenon has been explained thus: that cancer cells dominantly express death receptors while normal cells express decoy receptors. However, recent reports have shown that some cancer cell lines are resistant to TRAIL-induced apoptosis despite the absence of decoy receptors and the presence of death receptors. This suggested the existance of an inhibitory factor. We herein showed that NF-kappaB is a key molecule underlying the TRAIL-resistant mechanism in renal cell carcinoma (RCC) cell lines. We observed that NF-kappaB is constitutively activated in resistant cell lines. Forced expression of antisense cDNA of IkappaBalpha, a specific inhibitor of NF-kappaB, in TRAIL-sensitive cell lines with a low NF-kappaB activity result in constitutive activation of NF-kappaB and resistance to TRAIL-induced apoptosis. Adenoviral expression of a stable form of IkappaBalpha in the TRAIL-resistant cell lines induced apoptosis. These data suggest that RCC can be classified into two subsets: TRAIL-sensitive RCC with a low NF-kappaB activity and TRAIL-resistant RCC with constitutively activated NF-kappaB. In the former group TRAIL can be a treatment option, while in the latter group a molecular approach targeting NF-kappaB appears to be a promising therapy.

Antineoplastic Agents↗
PubMed2001

Interstitial photodynamic therapy with rotating and reciprocating optical fibers.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment modality that allows selective destruction of malignant tumor cells. However, because of the difficulty in exposing deeper areas of tumors, the modality has strictly limited indications. In this study, the authors introduce a new method for delivering laser light to a three-dimensional, wide area with the purpose of improving the therapeutic value of PDT. METHODS: Three patients with squamous cell carcinoma of the tongue were treated with the present course. After administering porfimer sodium, laser-proof tubes were inserted through the tumor, and optical fibers were passed through the tubes. Pulse laser was emitted from the obliquely prepared fiber tip and distributed toward the target area while rotating and reciprocating the optical fiber. RESULTS: Two patients achieved a complete response without any complications or functional disabilities. The third patient, however, had a partial response and required surgery. CONCLUSIONS: The results indicate the capability of distributing laser light to an entire area of solid tumor. However, the ideal dose of laser light for the treatment of tumors remains unknown. Interstitial PDT will be more efficacious and reliable after the dosimetry is established.

Aged↗
PubMed2001

Integrin alpha3beta1 engagement disrupts intercellular adhesion.

During tissue morphogenesis and tumor invasion, epithelial cells must undergo intercellular rearrangement in which cells are repositioned with respect to one another and the surrounding mesenchymal extracellular matrix. Using three-dimensional aggregates of squamous epithelial cells, we show that such intercellular rearrangements can be triggered by activation of beta1 integrins after their ligation with extracellular matrices. On nonadherent substrates, multicellular aggregates (MCAs) formed rapidly via E-cadherin junctional complexes and over time became compacted spheroids exhibiting a more epithelial phenotype. After MCAs were replated on culture substrates, the spheroids collapsed to yield tightly arranged cell monolayers. Cell-cell contact induced rapid elevation in E-cadherin levels, which was due to an increase in the metabolic stability of junctional receptors. During MCA remodeling of cell-cell adhesions, and monolayer formation, their E-cadherin levels fell rapidly. Similar behavior was obtained regardless of which ECM ligand-collagen type I, fibronectin, or laminin 1-MCAs were seeded on. In contrast, when seeded onto a matrix elaborated by squamous epithelial cells, cells in the MCA attached, spread, lost cell-cell junctions, and dispersed. Analysis identified laminin 5 as the active ECM ligand in this matrix, and MCA dispersion required functional beta1 integrin and specifically alpha3beta1. Furthermore, substrate-immobilized anti-integrin antibody effectively reproduced the epithelial-mesenchymal-like transition induced by the laminin 5 matrix. During the early stages of aggregate rearrangement and collapse, cells on laminin 5 substrates, but not those on collagen I substrates, exhibited intense cortical arrays of F-actin, microspikes, and fascin accumulation at their peripheral surfaces. These results suggest that engagement of specific integrin-ligand pairs regulates cadherin junctional adhesions during events common to epithelial morphogenesis and tumor invasion.

Antibodies, Monoclonal↗
PubMed2001

Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease.

We have studied the recruitment and roles of distinct dendritic cell (DC) precursors from the circulation into Propionibacterium acnes-induced granulomas in mouse liver. During infection, F4/80(-)B220(-)CD11c(+) DC precursors appeared in the circulation, migrated into the perisinusoidal space, and matured within newly formed granulomas. Recruited DCs later migrated to the portal area to interact with T cells in what we term "portal tract-associated lymphoid tissue" (PALT). Macrophage inflammatory protein 1alpha attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT. Anti-SLC antibody diminished PALT expansion while exacerbating granuloma formation. Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.

Animals↗
PubMed2001

Detection of IL-2 receptor gene expression in peripheral blood from renal transplant patients.

Cytokine monitoring is a potentially useful tool in the management of transplant patients. This study was conducted to analyze interleukin (IL)-1, tumor necrosis factor (TNF), IL-2, and IL-2 receptor gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in peripheral whole blood from healthy volunteers and patients who underwent laparotomy or renal transplantation. In the patients who underwent laparotomy, IL-1 and TNF expression was detected postoperatively, but IL-2 and IL-2 receptor expression was not. IL-1, TNF, and IL-2 receptor gene expression was detected in all the renal transplant patients, including those with signs of rejection. No cytokine gene expression was detected preoperatively, pretransplant, or in the healthy volunteers. We were able to discriminate transplantation from laparotomy by the cytokine profile. These results indicate that our method may be a useful tool for the immunological monitoring of transplant patients.

Adult↗
PubMed2001

Genomic analysis of a mouse model of immunoglobulin A nephropathy reveals an enhanced PDGF-EDG5 cascade.

The molecular mechanism of immunoglobulin A nephropathy (IgAN), the most common primary renal glomerular disease worldwide, is unknown. HIGA (high serum IgA) mouse is a valid model of IgAN showing almost all of the pathological features, including mesangial cell proliferation. Here we elucidate a pattern of gene expression associated with IgAN by analyzing the diseased kidneys on cDNA microarrays. In particular, we showed an enhanced expression of several genes regulating the cell cycle and proliferation, including growth factors and their receptors, as well as endothelial differentiation gene-5 (EDG5), a receptor for sphingosine 1-phosphate (SPP). One of the growth factors, platelet-derived growth factor (PDGF) induces a marked upregulation of EDG5 in proliferative mesangial cells, and promotes cell proliferation synergistically with SPP. The genomic approach allows us to identify families of genes involved in a process, and can indicate that enhanced PDGF-EDG5 signaling plays an important role in the progression of IgAN.

Animals↗
PubMed2001

Age-related prevalence of erectile dysfunction in Japan: assessment by the International Index of Erectile Function.

BACKGROUND: The effects of age and concomitant chronic illness on male sexual function were investigated to obtain insight into the prevention of erectile dysfunction (ED). METHODS: A questionnaire from the International Index of Erectile Function (IIEF) was given to 2311 non-institutionalized men aged 23-79 years along with a survey of health status. The study sample consisted of 1517 men who provided complete responses to the questionnaire. For statistical analysis, ANOVA was conducted to evaluate the effect of aging on the sexual functions and a logistic regression model was used to identify significant independent risk factors for ED. RESULTS: There was a significant correlation between age and the scores for erectile function, orgasmic function, sexual desire and intercourse satisfaction. The prevalence of moderate and severe cases of ED were 1.8% and 0% for ages 23-29; 2.6% and 0% for ages 30-39; 7.6% and 1.0% for ages 40-49; 14.0% and 6.0% for ages 50-59; 25.9% and 15.9% for ages 60-69; and 27.9% and 36.4% for ages 70-79 years, respectively. Hypertension, diabetes mellitus, heart disease, chronic hepatitis, disc herniation and cerebral infarction under treatment with anticoagulants were significant independent risk factors for ED. CONCLUSIONS: The results obtained indicated a significant association between aging and chronic diseases and erectile function. Further epidemiologic research and analysis of individual risk factors are required to allow more effective future strategies for the treatment and prevention of ED.

Adult↗
PubMed2001

Transurethral needle ablation of the prostate: an initial Japanese clinical trial.

OBJECTIVES: Transurethral needle ablation of the prostate is a new alternative endoscopic thermal therapy that uses a low-energy radio frequency delivered into the prostatic adenoma. Herein is reported the initial clinical experience by multiple institutes in Japan of transurethral needle ablation of the prostate for the treatment of symptomatic benign prostatic hyperplasia. METHODS: A total of 93 patients were treated with this technique. Transurethral needle ablation of the prostate was generally performed under low-spinal anesthesia. Before and after the procedure, international symptom score (IPSS), quality of life (QOL) score, peak urinary flow rate (Qmax), postvoid residual urine volume and prostate size were evaluated. RESULTS: There was a reduction of IPSS of more than 50% when compared with that of pretreatment, being 51.3% (57/93 patients) and 60.2% (56/93 patients) at 3 months and 6 months after the procedure, respectively. Sixty-seven patients who were available for a 12-month follow-up period demonstrated a markedly decreased mean IPSS when compared with that measured before the treatment for a statistically significant difference (P < 0.01). Fifty-eight patients who were available for uroflowmetric study at 12 months exhibited a notably increased mean Qmax of 11.2 +/- 4.5 mL/s, which was a statistically significant increase when compared with that found before treatment (P < 0.05). Although all patients suffered some degree of gross hematuria after the procedure, none of them required any specific treatment for complications. CONCLUSION: Transurethral needle ablation technique for the treatment of symptomatic benign prostatic hyperplasia is safe and effective. However, a much longer follow-up study is essential for fully evaluating the extended effectiveness of this technique.

Aged↗
PubMed2001

Brachytherapy for prostate cancer in Japan.

The temporary implantation of iridium-192 (Ir-192) is available in Japan if the patient is isolated in a radiation control area during the treatment. In this study, brachytherapy for prostate cancer was preceded by using low-dose rate Ir-192. Twenty-six patients with localized prostate cancer were treated with brachytherapy since December 1997. The age of patients ranged from 61 to 82 (median 76) years and the initial serum prostate-specific antigen (PSA) level ranged from 4.3 to 141 (median 17.4) ng/ml. Ten to 14 needles with Teflon sheaths were introduced into the prostate via a transperineal approach and an Ir-192 wire was placed in each sheath. The dose-distribution curve based on computed tomography imaging was drawn and the irradiation time was calculated for the whole prostate to receive over 70 Gy. During the 1-22-month follow-up period, all cases with an initial PSA level of less than 25 ng/ml showed continuous PSA decrease without biochemical failure. Magnetic resonance imaging demonstrated tumor regression in all cases within 6 months after the treatment. One-year biopsy specimens from patients with PSA failure demonstrated viable tumor cells, and the specimens from patients with favorable progress revealed fibrosis replacement without any variable tumor cells. Characterization of nocturnal penile tumescence data and IIEF 15 score proved the minimal effect of the treatment on erectile function. No major side effects or complications were observed. Brachytherapy using Ir-192 is a less invasive and safe procedure, which is expected to become a standard treatment for localized prostate cancer patients with relatively low PSA levels.

Aged↗
PubMed2001

Aging and erectile dysfunction: the role of aging and concomitant chronic illness.

Erectile dysfunction (ED) can have a strong negative effect on the well-being and quality of life of the sufferer. Many factors may contribute to the development of this disorder; age in particular and also concomitant chronic illnesses including neurological, hormonal, arterial and cavernosal factors. An understanding of the prevalence and characteristics of risk factors for ED is required, in order to establish effective therapeutic strategies. However, the prevalence of ED depends on the definitions used and the use of an internationally established scale for the assessment of male sexual function is necessary to facilitate the comparison of data between different countries. Further epidemiologic research and analysis of individual risk factors is required. Such studies will clarify the interactive effects of organic factors and their probable etiology with the general physical, sociocultural and psychologic status of patients. These efforts will make it possible to design more effective future strategies for the treatment and prevention of ED.

Aged↗
PubMed2001

Re-evaluation of the latent period of bladder cancer in dyestuff-plant workers in Japan.

BACKGROUND: The carcinogenesis of benzidine (BZ) and beta-naphthylamine (BNA) for bladder is well known. Although it was thought to be rare to develop occupational bladder cancer more than 20 years after the exposure to these chemicals, there are still new clinical cases even 30 years after exposure. The purpose of this study was to re-evaluate the latent carcinogenic period of BZ and BNA, in order to set the safety period after exposure for the health surveillance system. METHODS: The subjects were 236 dyestuff-plant workers in Tokyo, who had been exposed to these dyestuffs. The incidence of bladder cancer and its histopathology in this group was surveyed in the period from 1962 to 1996. RESULTS: Nineteen workers (8.1%) were found to have bladder cancers. The exposure period for these 19 patients was 82.0 +/- 50.2 months. The mean +/- SD latent period from the subjects' initial and final exposure until tumor development was 29.5 +/- 8.2 years and 20.1 +/- 10.6 years, respectively. Significantly, a negative correlation (Pearson) was observed between the exposure period and the latent period from the end of exposure to cancer onset (R = -0.544, P < 0.05). All tumors except one were transitional cell carcinoma. Flow cytometric analysis was performed in 11 patients and all of these patients had DNA aneuploidy. CONCLUSIONS: The latent periods of bladder cancer caused by BZ and BNA were longer than previously expected. It is necessary to survey the onset of bladder cancer in exposed workers more than 30 years after the initial exposure.

2-Naphthylamine↗
PubMed2001

Establishment of a testicular carcinoma cell line producing alpha-fetoprotein.

OBJECTIVE: To characterize a newly established human testicular carcinoma cell line that continuously produces alpha-fetoprotein (AFP), and to investigate the effects of retinoic acid on AFP production. MATERIALS AND METHODS: A 24-year-old man underwent a radical orchidectomy for a right testicular tumour and was found to have two separate metastatic lesions in the lungs, both of which were removed surgically. The cancer cells were isolated from one of the tumours, which was composed of undifferentiated germ cells and produced AFP; the cells were cultured in a monolayer. This cell line was designated as KU-MT. RESULTS: The cell line was successfully maintained both in athymic nude mice and in culture. Histological examination showed that the xenografted tumours were composed of cells in the reticular, solid and glandular patterns of a yolk sac tumour, and of embryonal carcinoma cells. These cells immunostained positively for AFP. On electron microscopy, the extracellular deposition of a basement lamina-like substance, a typical feature of yolk sac tumour, was detected. The AFP production in mice correlated well with the tumour weight of the xenograft. The cultured KU-MT cells were oval to polygonal in morphology and grew exponentially, with a population doubling time of approximately 2 days. Chromosomal analysis showed a modal number of 57 with consistent structural abnormalities of +add(1)(p13), del(1)(q32), del(2)(q31), add(6) (q21), +add(9)(p22), add(11)(p15), and add(14)(p11). Reverse-transcription polymerase chain reaction analysis showed that the retinoic acid receptors (RAR)-alpha, RAR-gamma, and retinoid X receptor-alpha were present in the cells. The expression of AFP mRNA was up-regulated in response to all-trans-retinoic acid; treatment with this agent caused morphological changes and induced apoptosis in the cells. CONCLUSIONS: This newly established cell line provides a reproducible model system that should offer a good insight into the differentiation of testicular carcinoma.

Adult↗
PubMed2001

Retroperitoneoscopic radical nephrectomy by the posterior lumber approach for renal-cell carcinoma associated with chronic renal failure.

PURPOSE: To evaluate the efficacy and invasiveness of retroperitoneoscopic radical nephrectomy for renal-cell carcinoma (RCC) in patients with chronic renal failure (CRF), a group known to have relatively high surgical risk. PATIENTS AND METHODS: Between May 1996 and September 1999, six CRF patients maintained on hemodialysis underwent retroperitoneoscopic radical nephrectomy for clinically localized RCC by the posterior lumber approach. The excised kidneys were evacuated via a posterior skin incision (5 cm) between two port sites; the muscle layers were not incised. RESULTS: The procedure was completed in all patients with no major complications. The mean operative time was 162 (range 135-210) minutes, and the estimated blood loss was 58 (15-100) mL; none of the patients required a blood transfusion. Regular hemodialysis was restarted on postoperative day 2 or 3. CONCLUSIONS: This procedure seems to be minimally invasive and suitable for the treatment of small RCC in atrophic kidneys, especially in patients with CRF.

Atrophy↗
PubMed2001

Expression of estrogen receptor (ER-alpha and ER-beta) mRNA in human prostate cancer.

OBJECTIVE: The distribution of the two estrogen receptors (ER-alpha, ER-beta) in human prostate tissue have not been fully clarified, so the present study investigated the mRNA expression of the receptors to explain the broad spectrum of estrogen activity in prostate cancer. MATERIALS AND METHODS: Four human prostate cancer cell lines (LNCap, JCA-1, DU-145 and PC-3) and 24 pairs of untreated prostate cancer tissue and noncancerous tissue from resected prostate glands were subjected to RT-PCR testing. RESULTS: Both LNCap and JCA-1 expressed the mRNA of both receptors, but DU-145 and PC-3 only expressed ER-beta mRNA. In the human prostate tissue samples, 20 of the 24 prostate cancer tissues expressed ER-alpha, and 23 of the 24 expressed ER-beta. Of the 24 noncancer tissues, 14 expressed ER-alpha mRNA and 17 expressed ER-beta mRNA. The incidence of ER-beta mRNA expression between the paired cancer and noncancer tissues was statistically significantly different (p<0.05). CONCLUSIONS: A higher incidence of ER-beta mRNA expression in untreated prostate cancer tissues was observed. Furthermore, the absence of ER-alpha mRNA and the presence of ER-beta mRNA expression in hormone-independent and/or untreated prostate cancer cells leads to a tentative speculation of the mechanism of the hormone refractory feature of prostate cancer.

Estrogen Receptor alpha↗