Biomedical subjects

K Shiraishi

Publications and source records attributed to K Shiraishi.

At least 19 recordsLinked to original sources

PubMed2006

Pre-B-cell leukemia transcription factor 1 is a major target of promyelocytic leukemia zinc-finger-mediated melanoma cell growth suppression.

Promyelocytic leukemia zinc-finger (PLZF) is a transcriptional repressor and tumor suppressor. PLZF is expressed in melanocytes but not in melanoma cells, and recovery of PLZF expression markedly suppresses melanoma cell growth. Several target genes regulated by PLZF have been identified, but the precise function of PLZF remains uncertain. Here, we searched for candidate target genes of PLZF by DNA microarray analysis. Pre-B-cell leukemia transcription factor 1 (Pbx1) was one of the prominently suppressed genes. Pbx1 was highly expressed in melanoma cells, and its expression was reduced by transduction with the PLZF gene. Moreover, the growth suppression mediated by PLZF was reversed by enforced expression of Pbx1. Knockdown of Pbx1 by specific small interfering RNAs suppressed melanoma cell growth. We also found that Pbx1 binds HoxB7. Reverse transcription-polymerase chain reaction analysis demonstrated that repression of Pbx1 by PLZF reduces the expression of HoxB7 target genes, including tumor-associated neoangiogenesis factors such as basic fibroblast growth factor, angiopoietin-2 and matrix metalloprotease 9. These findings suggest that deregulation of Pbx1 expression owing to loss of PLZF expression contributes to the progression and/or pathogenesis of melanoma.

Angiopoietin-2↗

PubMed2006

Radiation therapy combined with cis-diammine-glycolatoplatinum (nedaplatin) and 5-fluorouracil for Japanese stage II-IV esophageal cancer compared with cisplatin plus 5-fluorouracil regimen: a retrospective study.

To evaluate the treatment outcome of radiotherapy combined with cis-diammine-glycolatoplatinum (nedaplatin) plus 5-fluorouracil (5-FU) for esophageal cancer. From January 2000 to December 2004, a total of 12 esophageal cancer patients with locally advanced and metastatic esophageal cancer (stages II-IVB) were treated with radiation therapy (50.4 Gy) combined with nedaplatin (80 mg/m(2), bolus infusion) and 5-FU (800 mg/m(2)/24 h, continuous infusion for 4 days) (NDP group). We compared the data with those of patients during the same period receiving a different chemotherapy regimen consisting of cisplatin (75 mg/m(2), bolus infusion) and 5-FU (1000 mg/m(2)/24 h, continuous infusion for 4 days) (n = 29, CDDP group) combined with the same radiation therapy. The median survival period was 11.5 months in the NDP group and 13.1 months in the CDDP group. The overall survival rates at 1-, 2-, and 3-years were 40%, 13%, and 13% in the NDP group and 56%, 42%, and 8% in the CDDP group (P = 0.2472), respectively. Grade III and IV leukocytopenia was observed in six (50%) and none of the patients in the NDP group and 14 (48%) and seven (24%) in the CDDP group, respectively. Grade III thrombocytopenia was observed in three (25%) in the NDP group and four (14%) in the CDDP group. Radiation combined with nedaplatin and 5-FU is a safe and effective method for treating esophageal cancer. We recommend that NDP should be used rather than dose-reduction of CDDP combined with 5-FU in patients with impaired renal function as indicated by low creatinine clearance value (40-60 mL/min).

Adenocarcinoma↗

PubMed2005

Increased expression of Leydig cell haem oxygenase-1 preserves spermatogenesis in varicocele.

BACKGROUND: Oxidative stress is involved in the pathogenesis of testicular disorders. Haem oxygenase-1 (HO-1) plays an important cytoprotective role against oxidative stress. We investigated the presence of oxidative stress, represented by generation of 4-hydroxy-2-nonenal (4-HNE)-modified proteins, and expression of HO-1 in varicocele testes of human. METHODS: Thirty testicular biopsies from patients with left varicocele and 10 from patients with normal spermatogenesis were included. Generation of 4-HNE-modified proteins was examined as a marker of oxidative stress. Expression of HO-1 was assessed by western blotting and immunohistochemistry. The expression was compared with clinico-pathological parameters. RESULTS: Increased generation of 4-HNE-modified proteins was observed in varicocele testes. HO-1 expression was significantly correlated with varicocele grade (P < 0.01 in grade 2 and 3 compared to control) and expression of 4-HNE-modified proteins (r = 0.508, P < 0.01). The immunoreactivity was increased in Leydig cells in varicocele testes. There were significant correlations between age, total motile sperm count, Johnsen's mean score and HO-1:4-HNE-modified protein ratio (r = 0.206, 0.405 and 0.408, P = 0.027, 0.027 and 0.025 respectively). CONCLUSIONS: In testes with varicocele, there are increases in 4-HNE-modified proteins, suggesting that oxidative stress is present. Increased HO-1 expression, mainly in Leydig cells, is considered to protect the cells against oxidative stresses in varicocele testes.

Adult↗

PubMed2005

Salvage radiotherapy for postoperative loco-regional recurrence of esophageal cancer.

The aim of this paper is to evaluate the treatment outcome of radiation therapy (RT) for 16 loco-regionally recurrent esophageal cancer patients. Between 1995 and 2004, patients with loco-regional recurrence of esophageal cancer after curative surgery received RT with or without chemotherapy (CTx) at an average total dose of 56.6 Gy (n = 16, REC group). The site of recurrence was the supraclavicular region in three patients, the mediastinal region in nine patients, and both the supraclavicular and mediastinal regions in four patients. We compared the data with those of patients receiving palliative RT with or without CTx for mediastinal relapse, distant metastasis or malignant pleural effusion (n = 39, META group) and with those of patients receiving postoperative RT with or without CTx in a planned fashion 4-6 weeks after esophagectomy (n = 27, PORT group). The median survival period was 13.8 months in the REC group, 3.5 months in the META group, and 19.1 months in the PORT group. The survival rates at 1 and 2 years were 56% and 19% in the REC group, 6% and 3% in the META group (P = 0.0003), and 70% and 43% in the PORT group (P = 0.1917), respectively. According to univariate analysis, the factor of worse prognosis was not found in the REC group. Complete or partial responses were observed in four (25%) and nine (56%) of the REC group patients, respectively. In the REC group, changes in clinical symptoms, such as dysphagia and recurrent nerve paralysis, could be evaluated in eight patients, and improvement in symptoms was obtained in five (63%) patients. The prognosis of patients who received RT for postoperative loco-regional recurrence of esophageal cancer was significantly better than that of the META group patients and compatible with that of the PORT group patients. Additionally, there is symptomatic relief in a substantial proportion of such patients, and long-term survival is possible in some patients.

Adult↗

PubMed2005

Treatment results and prognostic analysis of radical radiotherapy for locally advanced cancer of the uterine cervix.

This study investigated treatment results and prognostic factors in radical radiotherapy for stage IIB-IVA cervical cancer. This is a retrospective analysis of 71 patients with cancer of the uterine cervix treated radically with external beam radiotherapy and high-dose-rate intracavitary brachytherapy between June 1991 and May 2004. In 47/71 (66%) of patients' chemotherapy was combined with radiotherapy. All 71 patients were retrospectively analysed. The median follow-up time was 34.8 months. The median age was 57 years (range 26-78 years) There were 21 patients (30%) in stage IIB, 3 (4%) stage IIIA, 40 (56%) stage IIIB, and 7 (10%) stage IVA. The 5-year overall survival rate was 83.5%, 77.0%, and 42.9% for stage IIB, III, and IVA, respectively. Federation Internationale de Gynocologie et d'Obstetrique (FIGO) classification stage and pelvic and para-aortic nodal status significantly affected survival in univariate analysis, but no treatment-related factor was found to be significant in multivariate analysis. In this study para-aortic nodal status was the most important prognostic factor in the radical radiotherapy of cervical cancer.

Adenocarcinoma↗

PubMed2003

Quantitative analysis of testicular interstitial fibrosis after vasectomy in humans.

PURPOSE: Germ cell differentiation, DNA synthesis, and apoptosis can be evaluated quantitatively. On the other hand, an interstitial lesion is difficult to examine. We have focused on the quantitative analysis of testicular interstitial fibrosis after vasectomy. MATERIALS AND METHODS: Forty testicular biopsy specimens from twenty consecutive men were obtained at vasovasostomy. Johnsen's mean score was calculated from testicular biopsy specimens. Percent of interstitial fibrosis was determined quantitatively by the NIH-Image after Masson-trichrome staining. RESULTS: A significant increase in interstitial fibrosis was observed along with the obstructive interval (p < 0.001). Johnsen's mean score count did not associate with the obstructive interval. CONCLUSION: Interstitial lesions of testicular physiology and pathophysiology can be evaluated using the NIH-Image. Interstitial fibrosis, but not the intraseminiferous status, reflects the irreversible damage of vasectomized testes.

Adult↗

PubMed2002

Elevation of serum KL-6 levels in patients with hematological malignancies associated with cytomegalovirus or Pneumocystis carinii pneumonia.

The level of serum KL-6 antigen has been reported to be a sensitive indicator of various interstitial pneumonitis, but in patients with hematological malignancies who were accompanied by infective interstitial pneumonitis like Pneumocystis carinii or cytomegalovirus (CMV) pneumonia, it is still unknown whether serum KL-6 level is useful as a good marker for the diagnosis or disease activity. In this study, the serum levels of KL-6 and soluble intercellular adhesion molecule 1 (sICAM-1) were evaluated in five patients with malignant lymphoma or adult T-cell leukemia. Serum KL-6 and sICAM-1 levels at the time of diagnosis of P. carinii or CMV pneumonia were 1220+/-323 U/ml (mean+/-SD) and 1246+/-485 ng/ml, respectively. These levels were apparently high, when compared with standard value of serum KL-6 (<520 U/ml) and that of sICAM-1 (115-306 ng/ml). In patients without P. carinii or CMV pneumonia, who had hematological malignancies or AIDS, serum level of KL-6 was not high (299+/-122 U/ml), but sICAM-1 was high (651+/-495 ng/ml) because of the elevation of sICAM-1 in four of five cases. These findings suggest that, in patients with hematological malignancies, serum level of KL-6 antigen rather than sICAM-1 may be useful in the evaluation of CMV or P. carinii pneumonia.

Aged↗

PubMed2001

Convenient formation of 4-hydroxyalk-2-en-1-one functionality via A knoevenagel-type carbon chain elongation reaction of aldehyde with 1-arylsulfinylalkan-2-one.

A highly functionalized four-carbon unit, 4-hydroxyalk-2-en-1-one functionality [R2CH(OH)CH=CHCOR1], was conveniently prepared by a reaction of an aldehyde (R2CH2CHO) with a 1-(arylsulfinyl)alkan-2-one [ArS(O)CH2COR1] in the presence of diethylamine (Knoevenagel condition). Other functional groups, such as carbonyl and hydroxy groups, in both of the alkyl chains (R1, R2) did not prevent this reaction. This reaction was used to conveniently prepare (+/-)-(11E)-13-hydroxy-10-oxooctadec-11-enoic acid (14), having cytotoxic activity, and its analogues from undec-10-enoic acid in good yield.

Journal Article↗

PubMed2001

Comparative genomic hybridization analysis of genetic aberrations associated with development and progression of biliary tract carcinomas.

BACKGROUND: Little is known about genetic aberrations associated with development and progression of biliary tract carcinomas. METHODS: To study chromosomal aberrations associated with development and progression of biliary tract carcinomas, the authors used comparative genomic hybridization to examine 50 such carcinomas. RESULTS: Gains in part or in whole of chromosomes 1q, 8q, and 20q and losses of 5q, 8p, 9p, and 18q were detected frequently in early stage (T1/T2 classification) biliary tract carcinomas (> or = 40% of 19 early stage tumors), and they also were found in advanced stage (T3/T4 classification) tumors. In particular, loss of 9p was the most frequently observed aberration in both early stage (15 of 19; 78%) and advanced stage tumors (21 of 31; 68%). The frequencies of gains of 7p12-p14 (P < 0.003), 7p21-pter (P < 0.007), and 7q31 (P < 0.01) differed significantly between biliary tract carcinoma with and without distant metastasis. Also, gains of 5p and 19q13 and loss of 6q14-q16 were more frequent in tumors with lymph node metastasis than in those without it (P < 0.02). CONCLUSIONS: It is likely that loss of 9p is one of the genetic aberrations critical for the development of biliary tract carcinoma, whereas gains of 5p, 7p, 7q, and 19q and loss of 6q are considered later events associated with tumor progression and are thought to confer metastatic potential to biliary tract carcinomas.

Adult↗

PubMed2001

Prognosis of acute acoustic trauma: a retrospective study using multiple logistic regression analysis.

OBJECTIVE: The prognosis for acute acoustic trauma (AAT) is difficult to predict. Multiple logistic regression analysis was used in this study to determine which factors were most strongly related to outcome for patients with AAT. METHODS: The study group was comprised of 52 patients (52 ears). Separate analyses were performed on the no change and partial recovery groups, and on the no change and full recovery groups. The following eight factors were examined as explanatory variables, age; number of days before the start of treatment; use of earplugs; drug therapy (adrenocortical hormones, low molecular weight dextrans, and vitamin B12), mean hearing levels at 0.5, 1, and 2 kHz (pure tone average, PTA), and mean hearing levels at 4 and 8 kHz (high tone average, HTA). RESULTS: Factors determined to be most strongly related to outcome were the number of days before the start of treatment, PTA, and HTA. No significant relation to outcome was determined for the five following factors, age; use of earplugs; and drug therapy (adrenocortical hormones, low molecular weight dextrans, and vitamin B12). CONCLUSION: Our results will increase the ability to prognosticate the outcome for AAT.

Acute Disease↗

PubMed2001

Internal spermatic vein diameter and age at operation reflect the response to varicocelectomy.

It was evaluated whether the diameter of internal spermatic veins (measured directly during operation) correlates with the clinical grade and treatment outcome following varicocelectomy. Fifty-seven consecutive men undergoing left varicocelectomy were included in the study, and spermatic vein diameter was compared with the response to the operation. The diameter appeared larger with increasing clinical grade (subclinical: 3.40 +/- 1.64 mm; grade 1 : 2.74 +/- 0.84 mm; grade 2 : 3.70 +/- 1.09 mm; grade 3 : 4.38 +/- 1.30 mm). In patients 30 years or older, spermatic vein diameter in men whose post-operative semen parameters were unchanged or worsened was statistically larger than that of patients whose post-operative semen parameters were improved, in terms of both sperm concentration (3.90 +/- 1.24 mm versus 2.84 +/- 0.94 mm; P < 0.05) and sperm motility (3.98 +/- 1.24 mm versus 2.67 +/- 0.67 mm, P < 0.01). Although the diameter of internal spermatic veins measured directly during operation correlated well with clinical grade, it is the diameter and patient's age at operation, but not clinical grade, that determine the reversibility of testicular injury following varicocelectomy.

Adult↗

PubMed2001

Nitric oxide promotes germ cell necrosis in the delayed phase after experimental testicular torsion of rat.

The purpose of this study is to determine whether inducible nitric oxide synthase (iNOS) is involved in the pathogenesis of testicular ischemia-reperfusion (I/R) injury in association with germ cell death, through either necrosis or apoptosis. Western blot analysis showed that iNOS expression was markedly increased 1 h after ischemia, and was accompanied by a huge nitric oxide (NO) production, as measured by the Griess method, with a peak at 48 h of reperfusion. Immunohistochemistry showed that iNOS was expressed predominantly in the macrophage-like cells infiltrated in the interstitial tissues of the testis. Intraperitoneal injection of aminoguanidine (AMG) (400 mg/day), the inhibitor of iNOS, reduced NO production by 57.7% at 96 h of reperfusion. Calpain activation and proteolysis of alpha-fodrin induced by I/R were inhibited by AMG. Germ cell apoptosis was demonstrated by in situ TUNEL and DNA fragmentation on agarose gel electrophoresis. Germ cell apoptosis was maximally induced at 24 h of reperfusion, and was not inhibited by AMG. NO produced by iNOS in the delayed phase of reperfusion promoted alpha-fodrin proteolysis, which is closely associated with necrosis. Inducible NOS inhibition combined with calpain inhibition may improve impaired spermatogenesis after testicular torsion.

Animals↗

PubMed2001

Estimation of dietary 232Th, 238U, cesium, and strontium intakes in Vietnamese people from different geographical regions.

Diet samples were collected to estimate dietary intakes of 232Th, 238U, cesium, and strontium for Vietnamese adults using duplicate portion studies and market basket studies. Average concentrations of 232Th, 238U, cesium, and strontium in diet samples were 4.0 ng/g-dry, 2.5 ng/g-dry, 41 ng/g-dry, and 4.5 ng/g-dry, respectively. Daily intakes per person for 232Th, 238U, cesium, and strontium were estimated to be 0.99 microg, 0.66 microg, 10 microg, and 1.2 mg, respectively. Daily intakes of 232Th, 238U, and cesium differed statistically between northern and southern of Vietnam, depending on geological conditions and food habits. However, intakes of the four nuclides were similar to the global averages.

Adult↗

PubMed2001

A comparison of DNA copy number changes detected by comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas.

Tumors arising from the liver, biliary tract and pancreas, which originate in the foregut and are in close anatomical proximity to each other, sometimes show similar histological features. No studies have focused on genetic similarities and differences between tumors of these organs. To elucidate the similarities and differences in DNA copy number alterations between tumors of these organs, we applied comparative genomic hybridization (CGH) to cancers of the liver (31 cases), biliary tract (42 cases) and pancreas (27 cases). Some alterations were common to tumors of all three organs, and some were preferential in certain types of tumor. Gains of 1q and 8q and losses of 8p and 17p were common to all tumors. In contrast, 13q14 and 16q losses were detected exclusively in hepatocellular carcinomas (HCCs; p < 0.01). The incidence of 17q21 gain and 5q loss was higher in biliary tract cancers than in the other two types (p < 0.05). Pancreatic cancers exhibited higher incidence of 5q14-q23 gain and 19p loss than tumors of other organs (p < 0.01). Gains of 7p, 7q, 12p and 20q and losses of 3p, 6q, 9p and 18q were frequent in both biliary tract and pancreatic cancers but rare in HCCs (p < 0.05). The present results suggest that although genes located at 1q, 8p, 8q and 17p are frequently involved in HCC, biliary tract and pancreatic cancer, at least some of the genes implicated in carcinogenesis are different between these three types. It is also suggested that CGH analysis is useful as a potential adjunct for the diagnosis and management of these tumors of organs that are anatomically close to one another.

Aged↗

PubMed2001

In vitro effects of environmental salinity and cortisol on chloride cell differentiation in embryos of Mozambique tilapia, Oreochromis mossambicus, measured using a newly developed 'yolk-ball' incubation system.

To examine the functional differentiation of chloride cells in the yolk-sac membrane of tilapia (Oreochromis mossambicus) embryos, we developed a 'yolk-ball' incubation system in which the yolk sac was separated from the embryonic body and subjected to incubation in vitro. The yolk-ball preparation consists of the yolk and the covering yolk-sac membrane, which contains a rich population of chloride cells. After appropriate cutting, the incision on the yolk ball healed during incubation in balanced salt solution for 3h, so that the yolk-sac membrane completely enclosed the yolk. Yolk balls prepared from freshwater-acclimated embryos were transferred either to fresh water or to sea water and incubated for 48 and 96 h to elucidate the morphological changes in the chloride cells in response to environmental salinity. The chloride cells in the yolk-sac membrane were larger in sea water than in fresh water. In yolk balls transferred to sea water, chloride cells often formed multicellular complexes characteristic of seawater-type chloride cells. In those transferred to fresh water, however, the cells were small and rarely formed such complexes. These responses of chloride cells were identical to those observed in intact embryos. Thus, chloride cells in the yolk-sac membrane could differentiate into the seawater type independent of the embryonic body. To examine the possible effects of exogenous cortisol on chloride cell differentiation, the yolk balls were incubated for 48 h in fresh water or sea water containing different doses of cortisol (0.1-10 microg x ml(-1)). Although chloride cells were consistently larger in sea water than in fresh water in all experimental groups, cortisol administration had no effect on chloride cell surface area in either medium. These findings indicate that the chloride cells in the yolk-sac membrane are equipped with an autonomous mechanism of functional differentiation that is independent of the embryonic endocrine and nervous systems. The yolk-ball incubation system established here is an excellent experimental model for further studies on chloride cell differentiation and function.

Animals↗

PubMed2001

[Multivariate analysis using quantitative methods to evaluate the subjective loudness of tinnitus].

Factors affecting the subjective loudness of tinnitus were analyzed using quantitative methods. One hundred and eighty-four patients with unilateral tinnitus were studied. Major factors affecting the subjective loudness of tinnitus were found to be subjective tinnitus pitch, annoyance, diagnosis, pitch-matched frequency, insomnia, age, tinnitus loudness level in dB HL, the duration of tinnitus and the tinnitus loudness level in dB SL at the first axis. Tinnitus pitch and pitch-matched frequency strongly affected the loudness of the tinnitus; high-pitch tinnitus and middle and low frequencies were associated with the subjective loudness of the tinnitus. In contrast, low-pitch tinnitus and a high frequency were associated with the subjective softness of the tinnitus. Thus, tinnitus pitch and pitch-matched frequency are inversely related. Sudden deafness and dizziness were associated with subjective softness of tinnitus, while hearing loss in elderly patients was associated with subjective loudness of tinnitus. Our results suggest that the level of annoyance from tinnitus and the subjective loudness of tinnitus are closely related. The relation between these factors should be considered when evaluating patients with tinnitus.

Female↗

PubMed2001

Vasectomy impairs spermatogenesis through germ cell apoptosis mediated by the p53-Bax pathway in rats.

PURPOSE: The pathophysiology of impaired spermatogenesis after vasectomy has not been completely investigated. We examined the role of p53 protein in cell cycle arrest and apoptosis of germ cells after vasectomy in the rat. MATERIALS AND METHODS: Eight-week old rats underwent bilateral vasectomy and the testes were harvested 1, 4, 8, 12 and 24 weeks after surgery. Germ cell apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) and electrophoresis assay of DNA fragmentation. Western blot analysis and immunohistochemistry were performed to examine the expression of p53, proliferating cell nuclear antigen, Bax, Bcl-2, p21WAF1/Cip1 and Gadd45. To evaluate spermatogenesis, testicular weight and percent of haploid cells flow cytometry was done. RESULTS: Spermatogenesis impairment was associated with increased p53 and decreased proliferating cell nuclear antigen expression at the delayed phase more than 8 weeks after vasectomy. The number of TUNEL positive germ cells was increased at the early 1-week and delayed phases after vasectomy. Bax but not p21WAF1/Cip1 or Gadd45 expression was increased. p53, Bax and TUNEL positive cells were co-localized in the seminiferous tubules. CONCLUSIONS: Spermatogenesis was impaired after vasectomy by apoptosis but not by cell cycle arrest. The p53-Bax pathway effects apoptosis in the delayed phase after vasectomy in some seminiferous tubules.

Animals↗

PubMed2001

Genetic analysis of an influenza B virus isolated from a patient with encephalopathy in Japan.

An influenza B virus, B/Saga/S172/99 (SAG99), was isolated from the nasopharynx of a patient with encephalopathy/encephalitis in Japan in 1999. To clarify the molecular characteristics of this virus, detailed analysis of the gene segments coding for the hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix protein (M) and non-structural protein (NS) was undertaken. All five genes of SAG99 showed high nucleotide and predicted amino acid similarities with those of recent non-encephalopathic strains isolated in the same epidemic season. Subsequent phylogenetic analysis revealed that all five gene segments of SAG99 analyzed in the present study were most similar to those of the recent Yamagata/16/88-like viruses. The hemagglutinin and neuraminidase proteins of SAG99 were each distinguished from those of recent epidemic strains by one characteristic amino acid substitution. These substitutions were not found in the previously reported encephalopathy/encephalitis-derived influenza B viruses, and we could not find any common characteristic amino acid changes in SAG99 and these viruses. Similarly, among the internal proteins studied, only the M2 protein of SAG99 was found to contain a single novel amino acid change when compared with other recent isolates. Thus, it was apparent that SAG99 contained very few amino acid differences when compared with other epidemic viruses. The association of recent B/Yamagata/16/88-like viruses with encephalitis/encephalopathy observed in the present study and previously suggest that these viruses may have a higher potential for causing neurological complications in certain individuals.

Child↗