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Biomedical subjects

K Sakata

Publications and source records attributed to K Sakata.

At least 217 records · Page 12Linked to original sources

Loss of heterozygosity at the DCC gene locus is not crucial for the acquisition of metastatic potential in oesophageal squamous cell carcinoma.

Tumour specimens from 111 patients with oesophageal squamous cell carcinoma were screened for loss of heterozygosity (LOH) at the deleted colorectal carcinoma (DCC) gene locus. DCC-LOH occurred in 10 of 61 informative cases (16%). No statistically significant correlation was observed between DCC-LOH and lymph node metastasis, histopathological grade or tumour stage. The survival of patients exhibiting DCC-LOH was not statistically different from that of patients without LOH. These results suggest that LOH at the DCC locus is not related to the acquisition of metastatic potential or the state of tumour cell differentiation in oesophageal squamous cell carcinoma.

Base Sequence↗

Impaired fibrinolysis early after percutaneous transluminal coronary angioplasty is associated with restenosis.

This study examined the role of fibrinolytic components in the process of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Seventy-two patients with single-vessel disease who underwent successful PTCA were prospectively selected. Tissue plasminogen activator (TPA), free plasminogen activator inhibitor-1 (free PAI-1), TPA/PAI-1 complex, and total PAI-1 antigen levels were measured before, at 1 week after, and at 3 months after PTCA. Six months after PTCA, the study patients were divided into two groups: 41 patients without restenosis and 31 patients with restenosis. There were no significant differences with regard to sex, age, coronary risk factors, or morphologic changes in the target lesions between the two groups. There were no significant differences in plasma TPA, TPA/PAI-1 complex, or total PAI-1 levels at each sampling period, or in the time courses between the two groups, except for total PAI-1 levels at 1 week after PTCA. Although no significant differences in free PAI-1 levels before PTCA were observed, free PAI-1 levels after PTCA in the patients with restenosis were significantly higher than those in the patients without restenosis. In addition, each group had a significant change in the time course of free PAI-1 levels. The results suggest that impaired fibrinolysis early after PTCA might affect the repair process of vascular injury, which leads to restenosis, and also that serial determination of free PAI-1 levels could help predict restenosis.

Angioplasty, Balloon, Coronary↗

Functional expression of GABA rho 3 receptors in Xenopus oocytes.

Homomeric rat GABA rho 3 receptors were expressed in Xenopus oocytes, and their pharmacological profile was investigated electrophysiologically. GABA activated the rho 3 receptors with an EC50 value of 7.5 microM and a Hill coefficient of 1.6. The GABA-induced current was not antagonized by bicuculline (100 microM), but was blocked by picrotoxin (IC50: 0.68 microM for 100 microM GABA). The current was almost insensitive to pentobarbital, diazepam and a neurosteroid, 3 alpha-OH-DHP. Many of the pharmacological properties of the rho 3 subunit were similar to those of the previously reported rat rho 1 and rho 2 subunits and GABAC receptors.

Animals↗

The immunosuppressant FK506 ameliorates ischaemic damage in the rat brain.

The effect of the immunosuppressant FK506 on ischaemic neuronal damage was studied in a rat model of transient cerebral ischemia induced by occlusion of both common carotid arteries in combination with hypotension for 10 min. Neuronal damage was assessed morphologically after 4 days of recovery. Treatment with FK506, given at a dose of 2 mg kg-1 by intraperitoneal injections 30 min prior to ischemia and once daily during recovery, decreased neuronal damage by 52% in the hippocampal CA1 region and by 48% in the temporal cortex. The protection was not due to diminished body temperature or a marked reduction of ischaemia-induced synaptic overflow of glutamate. We propose that FK506 decreases neuronal damage either by inhibiting calcineurin-mediated events or by preserving mitochondrial function.

Animals↗

Successful induction of severe destructive arthritis by the transfer of in vitro-activated synovial fluid T cells from patients with rheumatoid arthritis (RA) in severe combined immunodeficient (SCID) mice.

In order to investigate the role of pathogenic T cells in RA, the establishment of an RA model using patients' T cells is thought to be essential. In this study, multiple and severe destructive arthritis was established by transferring in vitro-stimulated synovial fluid T (SFT) cells from patients with RA through simultaneous injection into knee joint and peritoneal cavity of SCID mice without causing xenogeneic graft-versus-host disease (GVHD). Neither the transfer of unstimulated SFT cells nor sole i.p. injection was sufficient to induce severe arthritis. Interestingly, in contrast with SFT cells, in vitro-activated peripheral blood lymphocytes from RA patients failed to trigger such arthritis, suggesting that pathogenic T cells might be concentrated in synovial fluid of RA patients. This, the first severe arthritis model mimicking RA induced by RA patients' T cells, is expected to provide important information about RA pathogenesis and a possible therapeutic approach.

Aged↗

Histone hyperacetylation plays a role in augmentation of IL-4-induced IgE production in LPS-stimulated murine B-lymphocytes by sodium butyrate.

We previously reported the augmentation by sodium butyrate (NaBu) of IL-4-induced IgE production in LPS-stimulated murine B-lymphocytes. Histone deacetylase inhibition may be involved in the molecular mode of action of NaBu. Thus, this study was accomplished to examine the involvement of histone hyperacetylation in IL-4-induced class switching promotion by NaBu with a specific histone deacetylase inhibitor, trichostatin A (TSA). TSA was found to enhance IL-4-dependent IgE production in a concentration-dependent manner (0.3-30 nM) as did NaBu, although neither compound affected the IgE production in the absence of IL-4. The effect of combined addition of suboptimal concentrations of NaBu and TSA to the culture appeared to be additive, not synergistic. Moreover, the intense of enhancement of IgE production observed by addition of both compounds at optimal concentrations appeared to be equivalent to that obtained with each maximal concentration. Furthermore, enhancement of IgE production by TSA or NaBu was confirmed to be absolutely IL-4 dependent and was not due to the shift of kinetics. On the other hand, various cell cycle inhibitors such as caffeine and theophylline (G1 or G2-arrest), hydroxyurea (S-arrest), and colchicine (M-arrest), none of which have the ability to inhibit histone deacetylase, were shown to have no effect. These findings suggest that histone hyperacetylation plays an important regulatory role in the modification of IL-4-dependent class switching to C epsilon in LPS-stimulated murine B-cells by NaBu.

Animals↗

Retropharyngeal abscess after radiation therapy and cis-platinum, 5-fluorouracil treatment for nasopharyngeal carcinoma with collagen disease: report of two patients and a review of the literature.

Collagen disease are frequently associated with malignant tumors. Recently, radiotherapy combined with chemotherapy has been recommended for improving the efficacy of treatment for nasopharyngeal carcinoma. Two patients with nasopharyngeal carcinoma complicated by collagen diseases (dermatomyositis in one, and Sjögren's syndrome with mixed connective tissue disease in the other) were given radiotherapy combined with chemotherapy consisting of cis-platinum and 5-fluorouracil. Following this combination therapy, both patients developed retropharyngeal abscess and ulceration of the mucosal membrane on the posterior wall of the oropharynx; there was no tumor cell involvement. Because these injuries were more severe than would have been expected from radiotherapy alone, it is recommended that special attention be paid to combination therapy in patients with nasopharyngeal carcinoma complicated by collagen disease.

Antineoplastic Combined Chemotherapy Protocols↗

Echo-Doppler evaluation of reverse flow sign in the intrahepatic portal branches after surgery.

OBJECTIVE: The author's evaluated the clinical significance of the development of reversed portal flow after abdominal surgery other than portosystemic shunt procedure. SUMMARY BACKGROUND DATA: There have been several reports in regard to reversed portal flow demonstrated by pulsed Doppler ultrasonography, most of which were related to portal hypertension. To the authors' knowledge, this is the first report in which reversed portal flow also is present in patients who have undergone abdominal surgery other than portosystemic shunt procedure. METHODS: Preoperative and postoperative pulsed Doppler ultrasonographic examinations were performed in 126 patients who underwent abdominal surgery. Postoperatively, the portal flow direction was assessed in the right portal branch or the umbilical portion of the left portal branch. RESULTS: Of the 126 patients, reversed portal flow developed in 10 after surgery; 9 of them died of liver failure. CONCLUSIONS: The postoperative development of reversed portal flow is considered to have grave prognostic significance, indicating that the degree of postoperative liver damage is extremely critical.

Adult↗

Establishment and characterization of high- and low-lung-metastatic cell lines derived from murine colon adenocarcinoma 26 tumor line.

We established and characterized high- (LuM1) and low-lung-metastatic (NM11) cell lines derived from murine colon adenocarcinoma 26 tumor line. LuM1 cell line was established as a clonal cell line from a cultured cell mixture derived from a lung-metastatic nodule after 7 sequential subcutaneous transplantations of lung-metastatic tumors in the abdominal wall of BALB/c mice. NM11 cell line was established from a cultured cell mixture derived from a subcutaneous transplant of murine colon adenocarcinoma 26 tumor cells. LuM1 cells showed marked spontaneous lung metastases, but NM11 cells rarely did. High invasive potential of LuM1 cells was revealed by in vitro invasion assay using Matrigel reconstituted membranes. Rapid retraction was observed in monolayers of human umbilical vein endothelial cells and bovine aortic endothelial cells when LuM1 cells were added on the monolayers. Gelatin zymography and immunochemical examinations with monoclonal antibodies against gelatinase B (Mr 95,000 type IV collagenase) showed secretion of large amounts of the gelatinase by LuM1 cells.

Adenocarcinoma↗

Inactivation of the E-cadherin gene in primary gastric carcinomas and gastric carcinoma cell lines.

We investigated the E (epithelial)-cadherin gene for mutations and loss of heterozygosity (LOH) in 24 primary gastric carcinomas (12 differentiated and 12 undifferentiated types, including 3 signet-ring cell carcinomas), as well as 4 gastric carcinoma cell lines of the undifferentiated type (MKN-45, GCIY, HGC-27 and GT3TKB). We utilized PCR-SSCP and RT-PCR followed by direct sequencing to detect gene mutations and skipped exons, and RT-PCR-SSCP to examine LOH. In primary carcinomas, gene mutations or skipped exons were detected in 4 of 9 (44%) undifferentiated carcinomas of the scattered type, including 2 signet-ring cell carcinomas, and in none of the 3 undifferentiated carcinomas of the adherent type and 12 differentiated carcinomas. Demonstrated mutations of the E-cadherin gene included an 18 bp deletion (codon 418-423) and a 3 bp deletion (codon 400, calcium-binding domain), both located in exon 9. Skipping of exon 9 with a 1 bp insertion at codon 337, and skipping of exon 8 with a 1 bp deletion at codon 336, also were detected. LOH was confirmed in all of the carcinomas in which gene mutations or skipped exons (3/3 informative cases) were demonstrated. The MKN-45 cell line exhibited an 18 bp deletion at the exon 6-intron 6 boundary with loss of the wild-type allele, and 2 of the remaining 3 cell lines (HGC-27 and GT3TKB) had lost expression without detectable structural alteration of the E-cadherin gene. These data provide support for classic two-hit inactivation of the E-cadherin gene in a high percentage of undifferentiated carcinomas of the scattered type.

Alleles↗

Alterations of tumor suppressor genes and the H-ras oncogene in oral squamous cell carcinoma.

The frequencies of mutations in the adenomatous polyposis coli (APC). p53, and p16 (MTS1; multiple tumor suppressor 1/CDK4I; cyclin-dependent kinase 4 inhibitor) tumor suppressor genes were investigated in 23 oral squamous cell carcinomas (SCCs). Loss of heterozygosity (LOH) at the retinoblastoma (Rb) gene locus and on chromosomes 3p (VHL; von Hippel-Lindau disease tumor suppressor gene locus), 5q (APC) and 9p (p16), and H-ras oncogene mutations were also studied in the same samples. Techniques employed were polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP), DNA sequencing and PCR-microsatellite analyses. Mutations of the p53 gene were detected in 26% (6/23) of the tumor specimens. APC and p16 were not mutated in any of the 23 oral SCCs studied. LOH was detected in 17% (2/12 informative cases) at the Rb, in 33% (4/12) on 3p, in 17% (4/ 23) on 5q and in 30% (3/10) on 9p. Mutations of the H-ras gene were detected in 9% (2/23). The only correlation between these genetic alterations and clinicopathologic characteristics was that mutations of the p53 gene were detected more frequently in oral SCCs with lymph node metastasis than in those without it (P < 0.05). These results demonstrate that mutations of the p53 gene and LOH on 3p and 9p frequently occur in oral SCC and play important roles in the development and/or progression of this common malignancy.

Adult↗

Characteristics of vasospastic angina with exercised-induced ischemia--analysis of parameters of hemostasis and fibrinolysis.

To characterize the vasospastic angina patients with exercise-induced ischemia, we measured hemostasis (platelet factor 4; PF4, fibrinopeptide A; FPA) and fibrinolytic parameters (tissue plasminogen activator antigen; t-PA, free plasminogen activator inhibitor-1 antigen; free PAI-1) in 15 normal subjects and 33 vasospastic angina patients without significant coronary artery stenosis (less than 50% stenosis). All of the vasospastic angina patients began to feel chest pain within 3 months before diagnostic coronary angiography. Blood samples were obtained from all of the study patients at 8:30-9:30 am before exercise 201Tl emission computed tomography. Vasospastic angina patients were divided into 2 groups; 15 patients with exercise-induced ischemia (group 1) and 18 patients without exercise-induced ischemia (group 2). On coronary angiography, the severity of coronary artery stenosis at the site of spasm in group 1 (34 +/- 5%) was greater than that in group 2 (18 +/- 3%). Plasma FPA and PF 4 levels in group 1 were also significantly higher than those in normal subjects and group 2. Plasma t-PA and free PAI-1 levels in group 1 were significantly higher than those in normal subjects and group 2. Plasma levels of free PAI-1 group 2 were also significantly higher than those in normal subjects. The present study demonstrated that all of the patients with vasospastic angina had impaired fibrinolysis, and these patients with exercise-induced ischemia showed enhanced platelet activation, an enhanced coagulation system, and advanced atherosclerotic lesions. These results suggest that vasospastic angina with exercise-induced ischemia puts patients at increased risk for thrombus formation.

Adult↗

[A study on the relationship between sources of health information concerning smoking and drinking, and health behavior].

To determine effective measures to popularize knowledge on the health effects of smoking and drinking and to change health behavior, an interview survey of 2000 persons aged 18 or older randomly chosen from national census forms throughout Japan was carried out. The coverage rates of the information concerning smoking and drinking were 97.3% and 92.5%, respectively. Television, newspapers and magazines were the major sources of health information concerning smoking and drinking. In addition, men who gave up or controlled smoking or drinking usually obtained health information from doctors, while those who had never controlled smoking usually obtained health information from their friends and families. Men who could not control drinking effectively usually obtained health information from the health examination consultant at the workplace. However, according to the answers from men who gave up or controlled drinking, the health information useful in changing health behavior was obtained from the health examination consultant at the workplace and from persons who had a disease history. Women who gave up or controlled drinking answered that the health information from their friends and families was helpful to change the health behavior.

Adolescent↗

Cis- and trans-linalool 3,7-oxides and methyl salicylate glycosides and (Z)-3-hexenyl beta-D-glucopyranoside as aroma precursors from tea leaves for oolong tea.

Two new alcoholic aroma precursors, cis- and trans-linalool, 3,7-oxides 6-O-beta-D-apiofuranosyl-beta-D-glucopyranosides (1 and 2), as well as two already known compounds, (Z)-3-hexenyl beta-D-glucopyranoside (3) and methyl salicylate 6-O-beta-D-xylopyranosyl-beta-D-glucopyranoside (beta-primeveroside: 4), and another new monoterpendiol glycoside, 8-hydroxygeranyl beta-primeveroside (5) have recently been isolated as aroma precursors in tea leaves (Camellia sinensis var. sinensis cv. Maoxie) ready for oolong tea processing.

Carbohydrate Sequence↗

A human T-cell lymphotropic virus type-I carrier with chronic renal failure, aplastic anemia, myelopathy, uveitis, Sjögren's syndrome and panniculitis.

A 53-year-old female infected with human T lymphotropic virus type-I (HTLV-I) suffered from chronic renal failure, aplastic anemia, myelopathy, uveitis, Sjögren's syndrome and Weber-Christian disease. Although HTLV-I antibody was negative in cerebrospinal fluid, she was diagnosed as HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) based on clinical and histological findings. Though to date there is no direct evidence, other complications have also been reported to be HTLV-I related diseases. This case provided the unique opportunity to observe various HTLV-I related diseases.

Anemia, Aplastic↗

Relationships between smoking habits and other behavior factors among males: from the results of the 1990 National Cardiovascular Survey in Japan.

Relationships between smoking habits and other behavior factors such as habitual exercise, physical activities, and alcohol drinking habits were observed among Japanese males. Data used were obtained in The 1990 National Cardiovascular Survey in Japan, which consisted of 3826 males aged 30+ years selected from the Japanese population randomly. The proportion of current smokers was 53.5% in overall, and it decreased according to aging; these results were similar to Japanese former data. Those exercising habitually were more likely to be former smokers, whereas no relationship was observed between smoking habits and physical activities. Smoking and alcohol drinking habits were closely related; habitual drinkers were 3.34 times as likely to be current smokers as non-drinkers. Dose-response relationship was observed as well. Thus, the relationship between smoking and alcohol drinking habits was shown quantitatively.

Adult↗

Changes in cardiovascular disease risk factors in three Japanese national surveys 1971-1990.

Trends of cardiovascular disease risk factors were evaluated through comparison of three national surveys in Japan, 1971-1990. Data from three Japanese national surveys on circulatory disorders, conducted in 1971, 1980, and 1990, were analyzed. Variables common to the three national surveys were selected for analysis. Serum total cholesterol was also but was examined only in 1980 and 1990. Age- and sex-specific mean values, standard deviations, median values, and proportions in extreme categories were determined for all continuous variables and proportions in categories interest for all discrete variables. Trends from 1971-1990 and 1980-1990 were estimated by linear regression analysis for continuous variables, and logistic regression analysis for binary variables. Systolic blood pressure was decreasing constantly during three surveys in both men and women (beta = -0.22 in men and -0.34 in women, p < 0.01 in both). Total cholesterol was increasing rapidly in both men and women between 1980 and 1990 (beta = 1.27 in men and 1.41 in women, p < 0.01 in both). For other risk factors, the results were less consistent among age- or sex-specific groups. Continued monitoring of risk factor trends in Japan will be important for predicting and explaining future trends in the occurrence of coronary heart disease and stroke in this population.

Adult↗

Primary adult T cell leukemia of bone: two patients with primary bone lesion showing monoclonal integration of HTLV-I proviral DNA.

Adult T cell leukemia (ATL), a neoplasm of mature helper T lymphocytes is etiologically associated with human T lymphotropic virus type-I (HTLV-I). ATL cells infiltrate various organs, the lung, skin, central nervous system, gastrointestinal tract, and bone, causing various clinical manifestations. Two unusual cases of ATL, in which lytic bone lesion was the primary site of ATL, are described. One patient had multiple lytic lesions in bones without any involvement of other organs, and the other patient had a bone lesion in the right radius, which disappeared after chemotherapy. In both cases, monoclonal integration of HTLV-I provirus was demonstrated in the genomic DNA from each bone lesion. Although their clinical courses and pathological findings were different, ATL in both patients began as a bone lesion, showing that primary lymphoma of bone can be manifested in ATL cases.

Adult↗