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T Kishida

Publications and source records attributed to T Kishida.

At least 55 records · Page 3Linked to original sources

Role of chromosome 3p12-p21 tumour suppressor genes in clear cell renal cell carcinoma: analysis of VHL dependent and VHL independent pathways of tumorigenesis.

AIMS: Chromosome 3p deletions and loss of heterozygosity (LOH) for 3p markers are features of clear cell renal cell carcinoma but are rare in non-clear cell renal cell carcinoma. The VHL tumour suppressor gene, which maps to 3p25, is a major gatekeeper gene for clear cell renal cell carcinoma and is inactivated in most sporadic cases of this disease. However, it has been suggested that inactivation of other 3p tumour suppressor genes might be crucial for clear cell renal cell carcinoma tumorigenesis, with inactivation (VHL negative) and without inactivation (VHL positive) of the VHL tumour suppressor gene. This study set out to investigate the role of non-VHL tumour suppressor genes in VHL negative and VHL positive clear cell renal cell carcinoma. METHODS: Eighty two clear cell renal cell carcinomas of known VHL inactivation status were analysed for LOH at polymorphic loci within the candidate crucial regions for chromosome 3p tumour suppressor genes (3p25, LCTSGR1 at 3p21.3, LCTSGR2 at 3p12 and at 3p14.2). RESULTS: Chromosome 3p12-p21 LOH was frequent both in VHL negative and VHL positive clear cell renal cell carcinoma. However, although the frequency of 3p25 LOH in VHL negative clear cell renal cell carcinoma was similar to that at 3p12-p21, VHL positive tumours demonstrated significantly less LOH at 3p25 than at 3p12-p21. Although there was evidence of LOH for clear cell renal cell carcinoma tumour suppressor genes at 3p21, 3p14.2, and 3p12, both in VHL negative and VHL positive tumours, the major clear cell renal cell carcinoma LOH region mapped to 3p21.3, close to the lung cancer tumour suppressor gene region 1 (LCTSGR1). There was no association between tumour VHL status and tumour grade and stage. CONCLUSIONS: These findings further indicate that VHL inactivation is not sufficient to initiate clear cell renal cell carcinoma and that loss of a gatekeeper 3p21 tumour suppressor gene is a crucial event for renal cell carcinoma development in both VHL negative and VHL positive clear cell renal cell carcinoma.

Carcinoma, Renal Cell↗

Factor XII deficiency in women with recurrent miscarriage.

Congenital thrombophilia is known to cause significant maternal complications, and possibly has an adverse effect on normal fetal development. The aim of this study was to assess the prevalence of factor XII (FXII) deficiency in women with a history of recurrent miscarriage. Two hundred and forty-one consecutive Japanese women with a history of two or more recurrent miscarriages were prospectively assessed for their etiology by conventional screening methods. Seven women were found to have reduced FXII activity (19. 2-46.1%) and prolonged activated partial thromboplastin time (33. 3-51.3 s). Of these 7 women, 6 had experienced early pregnancy losses, while 1 woman had experienced repeated mid-trimester fetal losses with coincidental gestational thrombocytopenia. In 241 women with a history of recurrent miscarriage, the prevalence of FXII deficiency was 2.9%.

Abortion, Spontaneous↗

A practical quick staining method using hydrochloric acid-fast metachromatic dye for megakaryocytes.

A specific stain using violet polymethine dye (VPM stain) for megakaryocytes was first developed by Kass (1995). We have modified this method for practical use in bone marrow specimens. The modified VPM stain labels megakaryocytes very well, while other marrow cells are poorly colorized. This staining procedure was more stable, and its color intensity was finer and clearer than the original. Using this stain, morphologic classification of megakaryocytes in bone marrow specimens from 11 normal and 8 myelodysplastic syndrome (MDS) patients was performed. Many megakaryocytes observed in MDS patients were juvenile compared with normal subjects according to their morphology. Blasts from acute megakaryoblastic leukemia (M7) and from a megakaryoblastic cell line (Mo7e) were also clearly stained with our method. This staining method is practical and very useful for rapid identification of megakaryocyte distribution and morphology.

Bone Marrow Examination↗

Effect of dietary soy isoflavone aglycones on the urinary 16alpha-to-2-hydroxyestrone ratio in C3H/HeJ mice.

Estradiol is metabolized through two mutually exclusive pathways. 2-Hydroxyestrone (2-OHE,) is antiestrogenic, while 16alpha-hydroxyestrone (16alpha-OHE1) is a potent estrogen. It is suggested that a high urinary 16alpha-OHE1-to-2-OHE1 rato is a biomarker of increased mammary tumor risk. Mice were fed one of the test diets for 21 days. Indole-3-carbinol (2,500 mg/kg diet) increased the cytochrome P-450 content of hepatic microsomes and liver weight and reduced the urinary 16alpha-OHE1-to-2-OHE1 ratio in comparison with the respective value in the control mice. Fermented soy extract (100, 200, or 400 mg isoflavonoid/kg diet), genistein (200 mg/kg diet), and daidzein (200 mg/kg diet) each reduced the urinary 16alpha-OHE1-to-2-OHE1 ratio without increasing the cytochrome P-450 content of hepatic microsomes or liver weight. The combination of genistein and daidzein (100 mg and 100 mg/kg diet) did not have a synergistic effect on the reduction in urinary 16alpha-OHE1-to-2-OHE1 ratio. These data suggest that the soy isoflavonoid aglycones genistein and daidzein and indole-3-carbinol each exert a cancer-preventive effect by shifting metabolism away from the production of genotoxic metabolites toward the production of inactive metabolites.

Animals↗

[A 5 year follow-up study on the relationship between changes in serum lipids and blood pressure, and changes in exercise habits in subjects 30 years of age].

A 5 year follow-up study was conducted to investigate the relationships between %changes in serum lipids and blood pressure and corresponding changes in exercise habits in the middle-aged. The subjects were 152 males and 169 females who received a health check-up at 30-years-old during the period between 1990-1992 and then at 35-years-old during the period between 1995-1997. The results are as follows: 1. In multiple regression analysis, % delta toriglyceroid (TG) and % delta AI(atherogenic index) ratio were associated significantly with changes in exercise habits in males (P < 0.05) and % delta high density lipoprotein cholesterol (HDLC) was associated with changes in exercise habits in females (P < 0.05). % delta TG and % delta HDLC were affected by changes in exercise habits adjusted for BMI, smoking, and drinking. But changes in TC and blood pressure were not affected by changes in exercise habits. 2. In males, % delta TG was significantly lower in those subjects who started their exercise habit than in the no exercise group and than in those within the ceased exercise group who ceased their exercise during the study period (P < 0.05). % delta AI was significantly lower in the started exercise group than in the no exercise group. Also, the continued exercise group had a significantly (P < 0.05) lower % delta AI as compared to the ceased exercise group. In females, % delta TG was significantly lower in the started exercise group than in the no exercise group (P < 0.05). % delta HDLC was higher significantly in the continued exercise group than in the ceased exercise group (P < 0.05). From the results obtained, it is recommended that the no exercise subjects should have exercise more than once time per week and those with more than 1 time per week maintain their exercise habits.

Adult↗

[High-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of non-Hodgkin's lymphoma].

Findings for 41 patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and/or autologous peripheral blood stem cell transplantation (PBSCT) are reported. Two of the 41 patients were treated with HDC alone without PBSCT. At transplant, 20 patients were in complete remission, while 19 had resistant NHL and had failed to achieve a complete remission (CR) after several courses of conventional chemotherapy. The conditioning regimens used were mainly ACE (cytarabine, cyclophosphamide, etoposide) and MEAC (MCNU, etoposide, cytarabine, cyclophosphamide). The treatment-related mortality rate was 4.9%. Two patients treated with MEAC died from intractable congestive heart failure. Nine of the 19 patients with resistant NHL achieved CR, and at a median follow-up of 26 months (range, 3 to 93 months) the estimated two-year disease-free survival rate for these patients was 44.4%. Four patients in CR at present were in partial remission before HDC and PBSCT. Fifteen of the 20 patients in CR before HDC were transplanted in first CR and 5 in 2nd CR. At a median follow-up of 49 months (range, 3 to 96 months), the estimated 3-year DFS for the group of all patients was 73.7%. Five relapses occurred between 5 and 35 months post-transplantation. In conclusion, HDC and PBSCT as induction therapy was only effective for patients with resistant NHL who responded to conventional chemotherapy, and may improve the survival of patients in CR as consolidation therapy.

Adolescent↗

Risk of colorectal cancer in patients with hematologic disease.

BACKGROUND AND AIMS: A relatively large number of patients with multiple myeloma have been reported to develop a secondary malignancy such as cancer of the breast, biliary system or bowel. METHODS: A retrospective study was perfomed in 734 patients with hematologic disease diagnosed at Nippon Medical School Hospital between May 1984 and September 1994 to determine the incidence of colorectal cancer in these patients based on a history review, colonoscopic findings, and surgical or autopsy data. RESULTS: Of the 734 patients, 14 (1.9%) had colorectal cancer; two of 11 patients (18.2%) had pure red cell aplasia; two of 25 patients (8%) had multiple myeloma; and three of 46 patients (6.5%) had aplastic anemia. Patients with pure red cell aplasia, multiple myeloma or aplastic anemia had colorectal cancer at a significantly higher rate compared to those with leukemia (P< 0.005, P< 0.02, P< 0.01, respectively). CONCLUSIONS: It is possible that a relatively large number of patients with pure red cell aplasia, multiple myeloma or aplastic anemia will develop a colorectal cancer.

Aged↗

An important von Hippel-Lindau tumor suppressor domain mediates Sp1-binding and self-association.

VHL is the causative gene for both von Hippel-Lindau (VHL) disease and sporadic clear-cell renal cancer. We showed earlier that VHL downregulates vascular endothelial growth factor transcription by directly binding and inhibiting the transcriptional activator Sp1. We have now mapped the VHL Sp1-binding domain to amino acids 96-122. The 96-122 domain is disproportionately affected by substitution mutations, which interfere with the VHL-Sp1 interaction. Deletion of the 96-122 domain prevents VHL effects on Sp1 DNA binding and on VHL target gene expression, indicating the domain contributes importantly to VHL tumor suppressor activity. Nevertheless, prevention of the VHL-Sp1 interaction only partially abrogates VHL's transcriptional repressor activity, supporting the existence of VHL transcriptional effectors in addition to Sp1. VHL also directly interacts with the Sp1 zinc fingers and self-associates via the 96-122 domain, which furthermore suggest the domain may bind other metalloproteins and contribute to VHL dominant-negative effects.

Amino Acid Substitution↗

Direct interaction of the beta-domain of VHL tumor suppressor protein with the regulatory domain of atypical PKC isotypes.

VHL tumor suppressor protein contains two domains, alpha and beta. The alpha-domain is involved in the formation of a large protein complex suggested to be involved in ubiquitin-mediated protein degradation. However, the role of the beta-domain, which may recognize the target proteins for protein degradation, remains unknown. Here we report that the beta-domain interacts directly with atypical PKC isotypes, PKCzeta and PKClambda. Further, the regulatory domain of aPKC is sufficient for this direct protein-protein interaction. Since aPKC isotypes have been implicated in the regulation of cell growth and apoptosis, these results suggest that aPKC isotypes are potential direct target of the VHL beta-domain.

Amino Acid Sequence↗

Interaction of kyotorphin and brain peptide transporter in synaptosomes prepared from rat cerebellum: implication of high affinity type H+/peptide transporter PEPT2 mediated transport system.

High-affinity type H+/peptide cotransporter PEPT2 is preferentially expressed in the kidney, and is responsible for reabsorption of di- and tripeptides in epithelial tubules. Interestingly, PEPT2 has been recently cloned from rat brain. However, there is very little information available on the peptide transporter activity in the brain. In the present study, we investigated the interaction of kyotorphin (L-tyrosyl-L-arginine) with the peptide transporter using synaptosomes prepared from rat cerebellum. The activity of the peptide transporter was assessed by measuring the uptake of radiolabeled glycyl-sarcosine (Gly-Sar), which is a prototypical substrate for the peptide transporter, in the presence of H+-gradient. Kyotorphin competitively inhibited the uptake of Gly-Sar with an inhibitory constant (Ki) of 30 +/- 4 microM in rat cerebellum synaptosomes. This uptake property is very close to that of PEPT2. Carnosine (beta-alanyl-L-histidine) also inhibited the uptake of Gly-Sar, on the other hand, TRH did not interact with the peptide transporter. RT-PCR using specific primers revealed that PEPT2 mRNA exists in cerebellum in rat. Taken collectively, these results indicate that the functional peptide transport system in rat cerebellum might be the high affinity transporter PEPT2.

Animals↗

Recent trends in the prevalence of Down syndrome in Japan, 1980-1997.

The aims of the present study were to determine recent trends in the prevalence of Down syndrome (DS) in Japan, and to determine whether recent changes in demographic and social habits and access to prenatal diagnosis have influenced the livebirth rates of DS. Livebirth statistics indicate that the birth rate in Japan has decreased for women in their 20s and has increased for those in their 30s and 40s. During an 18-year period between 1980 and 1997, 1,299 consecutive DS infants were born among a total of 2,232,694 births, a rate corresponding to approximately 10% of all births in Japan over the same period. The increasing risk of DS with advancing maternal age was confirmed. The overall prevalence was 5.82 DS births per 10,000 livebirths (8.3-9.7 per 10,000 after correction according to the estimated ascertainment ratio: 60-70%). The prevalence rate by year of child birth represents a statistically significant increase (P = 0.001). In conclusion, recent trends in the prevalence of DS in Japan from 1980 to 1997 failed to show a consistent tendency to decrease, probably because of the concomitant increase in pregnancy in advanced maternal age.

Birth Rate↗

Changes in uterine size after vaginal delivery and cesarean section determined by vaginal sonography in the puerperium.

There have been few reports on postpartum changes in the uterus during the three months after delivery. The aim of this study was to evaluate uterine morphological changes in women after vaginal delivery (n=262-351) and in women after cesarean section (n=64-82) and to evaluate the relation between breast-feeding and parity, and uterine involution at 1 and 3 months postpartum measured by vaginal ultrasonography. There were no significant differences in parity between the vaginal delivery group and the cesarean section group. The length of the uterus at one month (7.93+/-1.16 cm, mean+/-SD) and, three months (7.03+/-1.19 cm) and the width of the uterus at three months (3.83+/-0.94 cm) after delivery in the cesarean section group were greater than in the transvaginal group (7.64+/-1.03 cm, 6.65+/-0.99 cm, 3.57+/-0.62 cm, respectively). Increasing maternal parity was associated slightly with larger uterine size at one month post partum. The length of the uterus of women with a breast-feeding rate of 80% or more per day was 6.35+/-0.85 cm, and shorter than in women with a rate of 20% or less 7.03+/-1.04 cm, at three months after delivery. The width of the uterine body of women with a breast-feeding rate of 80% or more per day was 3.32+/-0.45 cm, and shorter than in women with a rate of 20% or less 3.87+/-0.66 cm, at 3 months after delivery. Stepwise regression and multiple regression analysis among parity, the history of cesarean section, the breast-feeding rate at one and three months after the delivery, and the restoration of the menses at three months after the delivery showed that the uterine size at one month after the delivery was related to the cesarean section and that the uterine size at three months after delivery was mostly related to the rate of breast-feeding. These results indicated that uterine involution was related to delivery mode at one and three months postpartum, feeding mode at three months postpartum, the menses restoration, and parity. The rate of breastfeeding was mostly related to the uterine size at three months postpartum.

Adult↗

Serum iron and ferritin levels in patients with colorectal cancer in relation to the size, site, and disease stage of cancer.

We investigated blood loss from colorectal cancer in 92 men seen between January 1990 and June 1997, in relation to the size and site of the tumor, Dukes stage, pathologic type of cancer, and serum carcinoembryonic antigen (CEA) positivity. We used indirect methods, measuring serum hemoglobin, iron, and ferritin concentrations. The means of these three concentrations were significantly lower in patients with a tumor >3cm than in those with a tumor < or =3cm in largest diameter. The means of the three values were lower in patients with proximal colon cancer than in those with distal colon cancer, but only the difference in serum hemoglobin concentration was significant. Cancers of the ulcerative type were found more often in the proximal colon. The proportion of patients with Dukes stage C or D was not different between those with proximal colon cancer and those with distal colon cancer. There was a positive correlation between tumor size and Dukes stage. There were no differences in serum hemoglobin, iron, and ferritin concentrations with respect to the pathologic type of cancer and CEA positivity. These findings show that blood loss from colorectal cancer is closely related to the size and site of the tumor.

Adenocarcinoma↗

Superficial blood flow, blood volume, and blood velocity in colorectal tubular adenomas and adenocarcinomas.

To clarify differences in the vasculature of benign and malignant colorectal tumors, we compared blood flow (which has been examined in previous studies) as well as blood volume and blood velocity in two types of human colorectal tumors. We measured blood flow and blood volume with an endoscopic laser-Doppler flowmeter in the lesions and the normal mucosa near the lesions of 79 tubular adenomas with mild dysplasia and 38 adenocarcinomas. Blood velocity was defined as blood flow per blood volume. The ratio of each value in the lesions to that in the neighboring normal mucosa was defined as the relative value, and the mean relative values in the two groups were compared. The relative blood flow was 1.89 +/- 0.64 in the tubular adenomas and 1.49 +/- 0.66 in the adenocarcinomas (P < 0.005), and the relative blood volume was 1.10 +/- 0.14 and 0.90 +/- 0.13, respectively (P < 0.001). The relative blood velocity was approximately 1.7 in both groups (NS). This study demonstrated that the superficial blood flow in adenocarcinomas is increased due to increased blood velocity, despite blood volume being decreased.

Adenocarcinoma↗

Expression of von Hippel-Lindau protein in normal and pathological human tissues.

To examine the localization of von Hippel-Lindau (VHL) protein in human tissues, we produced four novel monoclonal antibodies against human VHL protein. Western blot analysis revealed that two of these antibodies recognized the epitope in amino acid sequence 60-89 of the VHL protein and the others recognized sequences 54-60 and 189-213. In a wild-type VHL gene-transfected cell line, immunocytochemistry and immunoelectron microscopy demonstrated the intracytoplasmic localization of VHL protein, particularly in mitotic cells. In normal human tissues, VHL protein was detected immunohistochemically in epithelial cells covering the body surface and the alimentary, respiratory, and genitourinary tracts; in secretory epithelial cells of exocrine and endocrine organs; in parenchymal cells of visceral organs; in cardiomyocytes; in neurons in nervous tissue; in lymphocytes in lymphoid tissue; and in macrophages. In pathological specimens, VHL protein was expressed in VHL-related tumor, as well as in endothelial cells, fibroblasts, and pericytes, all of which are involved in active angiogenesis. These findings suggest that these monoclonal antibodies can be useful for various immunological assays and that the VHL protein plays fundamental roles in physiological and pathological situations, especially in neovascularization.

Adolescent↗

Passive immune thrombocytopenia in neonates of mothers with idiopathic thrombocytopenic purpura: incidence and risk factors.

The aim of this study was to evaluate risk factors for occurrence of neonatal passive immune thrombocytopenia (PIT) in pregnancy complicated by idiopathic thrombocytopenic purpura (ITP). We studied 63 pregnant women with ITP and the 66 neonates retrospectively. Neonatal platelet counts were compared with maternal platelet counts, platelet-associated gamma G immunoglobulin (PAIgG) values, and the presence of antiplatelet antibody in the maternal circulation, history of previous PIT, maternal treatments for ITP, and other maternal or neonatal factors. PIT (platelet counts <100 x 10(3)/microL) was observed in 9 (14.3%) of 63 pregnancies. Presence of circulating antiplatelet antibody in maternal blood, splenectomy prior to pregnancy, and history of previous PIT were observed more frequently with statistical significance in patients giving birth to neonates who developed PIT. No effect on occurrence of PIT was found by the administration of corticosteroids or immunoglobulin. Splenectomy prior to pregnancy was found by logistic regression analysis to be a single significant variable (p = 0.021, odds ratio 7.20, confidence intervals: 1.35 to 38.3) among the risk factors for PIT.

Adrenal Cortex Hormones↗

Morphological aspects of ectopia cordis: four case reports and a review of the literature.

Ectopia cordis is a rare congenital anomaly. We present 4 cases of ectopia cordis, 1 of which is the first report of an affected fetus in a triplet pregnancy. The morphological relationship between the types of ectopia cordis and their outcomes were investigated in all 4 cases. In addition, the literature on ectopia cordis in Japan was reviewed and discussed.

Adult↗