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S Okada

Publications and source records attributed to S Okada.

At least 109 records · Page 6Linked to original sources
PubMed2001

Progression of T cell lineage restriction in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity.

The proximal promoter of lck directs gene expression exclusively in T cells. To investigate the developmental regulation of the lck proximal promoter activity and its relationship to T cell lineage commitment, a green fluorescence protein (GFP) transgenic (Tg) mouse in which the GFP expression is under the control of the proximal promoter of lck was created. In the adult GFP-Tg mice, >90% of CD4(+)CD8(+) and CD4(+)CD8(-) thymocytes, and the majority of CD4(-)CD8(+) and CD4(-)CD8(-) [double-negative (DN)] thymocytes were highly positive for GFP. Slightly lower but substantial levels of expression of GFP was also observed in mature splenic T cells. No GFP(+) cells was detected in non-T lineage subsets, including mature and immature B cells, CD5(+) B cells, and NK cells, indicating a preserved tissue specificity of the promoter. The earliest GFP(+) cells detected were found in the CD44(+)CD25(-) DN thymocyte subpopulation. The developmental potential of GFP(-) and GFP(+) cells in the CD44(+)CD25(-) DN fraction was examined using in vitro culture systems. The generation of substantial numbers of alphabeta and gammadelta T cells as well as NK cells was demonstrated from both GFP(-) and GFP(+) cells. However, no development of B cells or dendritic cells was detected from GFP(+) CD44(+)CD25(-) DN thymocytes. These results suggest that the progenitors expressing lck proximal promoter activity in the CD44(+)CD25(-) DN thymocyte subset have lost most of the progenitor potential for the B and dendritic cell lineage. Thus, progression of T cell lineage restriction in the earliest thymic population can be visualized by lck proximal promoter activity, suggesting a potential role of Lck in the T cell lineage commitment.

Animals↗
PubMed2001

Phase I trial of gemcitabine in patients with advanced pancreatic cancer.

BACKGROUND: Gemcitabine is the most promising new agent currently being tested in pancreatic cancer. The present study was conducted to confirm the tolerability of a weekly schedule of gemcitabine at a dose of 1000 mg/m2 in Japanese patients with advanced pancreatic cancer. METHODS: The primary end-point was to evaluate the frequency of dose-limiting toxicity. Gemcitabine 1000 mg/m2 was administered over 30 min weekly in two schedules: gemcitabine x3 every 4 weeks (Schedule 1) and gemcitabine x7 followed by a week of rest and then gemcitabine x3 every 4 weeks thereafter (Schedule 2). At least three patients entered each schedule and three additional patients were treated in the presence of dose-limiting toxicity. RESULTS: Eleven chemo-naive patients with a good Karnofsky performance status of > or =80 points and distant metastasis were entered into this trial. In Schedule 1, no dose-limiting toxicity was observed in the three patients. In Schedule 2, the evaluation of dose-limiting toxicity was complete in six of the eight enrolled patients and two patients showed dose-limiting toxicity in this Schedule; one patient experienced both grade 4 leukocytopenia and grade 4 neutropenia, and both grade 4 neutropenia and grade 3 GOT/GPT increased in another patient. Two patients (18%) showed a partial response and a clinical benefit response was also achieved in two (29%) of the seven evaluable patients. CONCLUSION: Gemcitabine 1000 mg/m2 weekly x7 followed by a week of rest and weekly x3 every 4 weeks thereafter may be tolerated in Japanese patients with advanced pancreatic cancer.

Adult↗
PubMed2001

Radiofrequency ablation and percutaneous ethanol injection in patients with small hepatocellular carcinoma: a comparative study.

BACKGROUND: Radiofrequency ablation (RFA) is a novel thermal ablation technique to achieve coagulative necrosis of hepatocellular carcinoma. A study was conducted to compare the antitumor effect and adverse effect of RFA with those of percutaneous ethanol injection (PEI) in patients with solitary small hepatocellular carcinoma. METHODS: The study population consisted of 119 consecutive patients with solitary hepatocellular carcinoma smaller than 3 cm in diameter. Among these, 23 patients were treated with RFA and the remaining 96 patients were treated with PEI. The antitumor effects of both treatments were assessed by contrast-enhanced computed tomography 1 month after treatment. RESULTS: Complete tumor necrosis was achieved in 23 patients (100%) of the RFA group and 90 patients (94%) of the PEI group (p = 0.48) and local recurrence rates at 1 year were 15% in the RFA group and 14% in the PEI group (p = 0.80). RFA required an average of 1.5 sessions to achieve complete necrosis, whereas PEI required an average of 4.0 sessions. As a consequence, the hospital stay in the RFA group (median 10 days) was significantly shorter than that in the PEI group (median 17 days). There were no serious adverse effects or complications except for one case of cholangitis in the PEI group, although deterioration of serum transaminase after RFA was significantly more severe than that after PEI. CONCLUSION: RFA achieved complete tumor necrosis for small hepatocellular carcinoma with fewer treatment sessions compared with PEI. There were no serious complications.

Adult↗
PubMed2001

Spontaneous regression of hepatocellular carcinoma with multiple lung metastases: a case report.

Spontaneous regression of hepatocellular carcinoma is an extraordinarily unusual phenomenon. We present here a case of a 75-year-old man in whom multiple lung metastases of hepatocellular carcinoma regressed spontaneously. He underwent systemic chemotherapy for hepatocellular carcinoma with multiple lung metastases. However, the chemotherapy was not effective and he was therefore followed up without any anticancer treatments in an outpatient clinic. Four months later, multiple lung nodules regressed dramatically and the serum alpha-fetoprotein level decreased markedly. After an 8-month period of the regression, however, intrahepatic lesions gradually enlarged, although multiple lung metastatic lesions remained regressed. The mechanisms underlying this intriguing phenomenon remain unknown.

Aged↗
PubMed2001

Prospective study of mother-to-infant transmission of hepatitis C virus.

BACKGROUND: Mother-to-infant transmission of hepatitis C virus (HCV) could become the main route of HCV infection in the future because there are no methods available to prevent vertical infection. The aim of this study was to determine the incidence of mother-to-infant transmission in infants born to mothers who tested positive for anti-HCV antibodies and to elucidate associated risk factors for transmission. METHODS: Screening was conducted for 16,800 pregnant women with an anti-HCV antibodies test, and 154 mothers were positive. From the positive group 141 mothers were enrolled in the study and their 147 infants were followed from birth for serum alanine aminotransferase activity, anti-HCV antibodies and HCV RNA. HIV infection was tested in 73 of 141 mothers, all of whom were negative. RESULTS: Thirty-three infants were dropped from the study because they were followed for <6 months or were not tested adequately. Of the 114 infants finally evaluated 9 (7.8%) had detectable HCV RNA. The transmission rate was not influenced by the mode of delivery [vaginal delivery, 8 of 90 vs. cesarean section, 1 of 24 (P = 0.396)] or by the type of feeding [9 of 98 for breast-fed infants vs. 0 of 16 for formula-fed infants (P = 0.243)]. All infected infants were born to mothers who had HCV viremia at the delivery (P = 0.040) and to those with a high viral load (P = 0.019). CONCLUSIONS: Our prospective study showed that the transmission rate of mother-to-infant HCV infection was 7.8% in anti-HCV antibody-positive mothers. Risk was related to the presence of maternal HCV viremia at delivery and a high viral load in the mothers.

Alanine Transaminase↗
PubMed2001

Abdominal pain in patients with resectable pancreatic cancer with reference to clinicopathologic findings.

Abdominal and/or back pain is one of the most common symptoms in patients with pancreatic cancer. However, the cause of the pain and the clinicopathologic features of patients with pain have not been fully elucidated. We retrospectively determined the factors related to preoperative abdominal and/or back pain in 95 patients with resectable pancreatic cancer. Pancreatic tumor size, invasion of the intrapancreatic nerves, invasion of the anterior pancreatic capsule, and lymph node metastasis were determined to be variables related to the pain. Pancreatic tumor size, invasion of anterior pancreatic capsule, and lymph node metastasis were also variables significantly correlating to pain intensity. Survival also correlated with pain intensity: the median survival periods were 29 months in patients without pain, 19 months in those with mild pain, and 9 months in those with severe pain who required analgesics. Larger pancreatic tumors, invasion of the intrapancreatic nerves, and invasion of the anterior pancreatic capsule may cause abdominal and/or back pain in patients with resectable pancreatic cancer. This study also suggests clinical implications of the pain intensity as a prognostic factor in patients with resectable pancreatic cancer.

Abdominal Pain↗
PubMed2001

Comparative study of the cyclization reactions of three bacterial cyclomaltodextrin glucanotransferases.

The actions of cyclomaltodextrin glucanotransferases (CGTase; EC 2.4.1.19) from alkalophilic Bacillus sp. strain A2-5a (A2-5a CGTase), Bacillus macerans (Bmac CGTase), and Bacillus stearothermophilus (Bste CGTase) on amylose were investigated. All three enzymes produced large cyclic alpha-1,4-glucans (cycloamyloses) at the early stage of the reaction, but these were subsequently converted into smaller cycloamyloses. However, the rates of this conversion differed among the three enzymes. The product specificity of each CGTase in the cyclization reaction was determined by measuring the amount of each cycloamylose from CD6 to CD31 (CDn, a cycloamylose with a degree of polymerization of n). A2-5a CGTase produced 10 times more CD7, while Bmac CGTase produced 34 times more CD6 than other cycloamyloses. Bste CGTase produced 12 and 3 times more CD6 and CD7 than other cycloamyloses, respectively. The substrate specificities of the linearization reactions of CD6, CD7, CD8, and larger cycloamyloses (a mixture of CD22 to CD50) were investigated, and we found that CD7 and CD8 are extremely poor substrates for both hydrolytic and transglycosidic linearization (coupling) reactions while larger cycloamyloses are linearized at a much higher rate. By repeating these cyclization and linearization reactions, the larger cycloamyloses initially produced are converted into smaller cycloamyloses and finally into mainly CD6, CD7, and CD8. These three enzymes also differ in their hydrolytic activities, which seem to accelerate the conversion of larger cycloamyloses into smaller cycloamyloses.

Amylose↗
PubMed2001

Frequent detection of the human herpesvirus 6-specific genomes in the livers of children with various liver diseases.

This study was performed to investigate the frequency of human herpesvirus 6 (HHV-6) infection of the liver in children with a variety of liver diseases and to evaluate the role of HHV-6 infection in pediatric patients with prolonged non-B non-C hepatitis. Detection of the HHV-6 genomes in liver, in peripheral blood mononuclear cells (PBMC), and in plasma was performed by PCR or by in situ hybridization. Liver biopsy materials from 48 patients, in whom HHV-6 infection was serologically confirmed, were available for PCR analysis. Sequences of the HHV-6B genome were detectable in the livers of 36 of 48 patients (75%). The presence of the genome was not associated with serum transaminase activities. The genome was detectable in PBMC of 22 of 31 (71%) patients tested. In these 31 patients HHV-6 was detected in both the livers and PBMC of 20, was detected in PBMC but not in the livers of 2, was detected in the livers but not in PBMC of 3, and was detected in neither of samples of 6. In situ hybridization of the livers of six patients showed the presence of the HHV-6B genome in the nuclei of hepatocytes. The anti-HHV-6 immunoglobulin M antibody was detectable in 2 of 9 of the non-B non-C hepatitis patients, whereas none of the 22 patients with etiology-defined liver diseases tested positive. Cell-free viral DNA was not detectable in either group of patients. Our results showed that HHV-6B is frequently present in the livers of children with a variety of liver diseases but do not support the assumption that HHV-6B infection of the liver is associated with prolonged non-B non-C hepatitis.

Adolescent↗
PubMed2001

Mitochondrial coupling factor 6 as a potent endogenous vasoconstrictor.

We demonstrated recently that coupling factor 6, an essential component of the energy-transducing stalk of mitochondrial ATP synthase, suppresses the synthesis of prostacyclin in vascular endothelial cells. Here, we tested the hypothesis that coupling factor 6 is present on the cell surface and is involved in the regulation of systemic circulation. This peptide is present on the surface of CRL-2222 vascular endothelial cells and is released by these cells into the medium. In vivo, the peptide circulates in the vascular system of the rat, and its gene expression and plasma concentration are higher in spontaneously hypertensive rats (SHRs) than in normotensive controls. Elevation of blood pressure with norepinephrine did not affect the plasma concentration of coupling factor 6. Intravenous injection of recombinant peptide increased blood pressure, apparently by suppressing prostacyclin synthesis, whereas a specific Ab to coupling factor 6 decreased systemic blood pressure concomitantly with an increase in plasma prostacyclin. Interestingly, the antibody's hypotensive effect could be abolished by treating with the cyclooxygenase inhibitor indomethacin. These findings indicate that mitochondrial coupling factor 6 functions as a potent endogenous vasoconstrictor in the fashion of a circulating hormone and may suggest a new mechanism for hypertension.

Amino Acid Sequence↗
PubMed2001

Testicular germ cell apoptosis in Bcl6-deficient mice.

Bcl6 protein has been detected in testicular germ cells, mainly spermatocytes, of normal mice, but its physiological role is largely unknown. The number of spermatozoa in the cauda epididymis of adult Bcl6-deficient (Bcl6-/-) mice is lower than that of Bcl6+/+ mice. We have found numerous apoptotic spermatocytes at the metaphase I stage with induction of Bax protein in adult Bcl6-/- testes. Developmentally, the incidence of germ cell apoptosis of Bcl6-/- mice was similar to that of Bcl6+/+ mice until six weeks of age and increased after eight weeks of age. The incidence of apoptosis in heterozygous Bcl6+/- mice was also higher than that of Bcl6+/+ mice. Since the activated form of p38 MAP kinase was detected in spermatocytes of adult Bcl6-/- mice, the germ cell apoptosis may be induced by stressors. Treatment of testes of adult Bcl6+/+ mice with a mild hyperthermia resulted in germ cell apoptosis predominantly in metaphase I spermatocytes with induction of Bax protein and activation of p38 MAP kinase and this apoptosis mimics that in adult Bcl6-/- mice. Thus, Bcl6 may play a role as a stabilizer in protecting spermatocytes from apoptosis induced by stressors.

Animals↗
PubMed2001

Antidiabetic effect of glycyrrhizin in genetically diabetic KK-Ay mice.

We, previously demonstrated that one shot administration of glycyrrhizin (Grz) reduced the postprandial blood glucose rise, using Std ddY mice. Subsequently, we evaluated the effects of long-term Grz treatment (2.7, 4.1 g/kg diet) on diabetic symptoms using genetically non-insulin dependent diabetic model mice (KK-Ay). Male KK-Ay mice were divided into 3 groups: the control group, 0.27% Grz diet (2.7 g of Grz/kg diet) group and 0.41% Grz diet (4.1 g of Grz/kg diet) group. The elevation of blood glucose concentration was almost entirely suppressed in mice fed the 0.41% Grz diet 7 weeks after the beginning of test feeding, although it was not suppressed in mice fed the control diet or the 0.27% Grz diet. Water intake in the control and 0.27% Grz diet groups increased gradually, whereas, this was not true in the 0.41% Grz diet group. Grz treatment significantly lowered blood insulin level. Throughout the experiment, Grz did not affect the food intake or body weight among the three groups. The mice fed the 0.41% Grz diet also improved their tolerance to oral glucose loading 9 weeks after the beginning of test feeding. This study shows that Grz has an antidiabetic effect in noninsulin-dependent diabetes model mice.

Animals↗
PubMed2001

Oral administration of dimethylarsinic acid, a main metabolite of inorganic arsenic, in mice promotes skin tumorigenesis initiated by dimethylbenz(a)anthracene with or without ultraviolet B as a promoter.

Concerning arsenic-induced tumorigenesis, an animal model must be developed for understanding the mechanism of human carcinogenesis by arsenics. To determine whether orally administered dimethylarsinic acid (DMA) promotes and causes the progression of skin tumorigenesis, an animal protocol by topical application of dimethylbenz(a)anthracene (DMBA) with or without UVB, a tumor promoter, in hairless mice was used. The administration of DMA by the oral route promoted not only the formation of papillomas induced by DMBA alone but also the formation of malignant tumors induced by way of the formation of atypical keratoses by treatment with DMBA and UVB. A phenomenon, the progression of keratoses-->atypical keratoses-->squamous cell carcinomas (SCCs), observed in the present study may resemble the development of tumors in arsenic-exposed humans. We also discussed the involvement of a reactive oxygen species (ROS), e.g., the dimethylarsenic peroxy radical [(CH3)2AsOO.], produced during the metabolic processing of DMA, in skin and in multi-organ tumorigenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Hyaluronate depolymerization following thermal decomposition of oxytetracycline.

Depolymerization of sodium hyaluronate (HA) by tetracyclines was investigated. Reduction in HA molecular weight was followed by size exclusion chromatography with a low angle laser light scattering detector. On mixing with oxytetracycline hydrochloride (OTC) solution and incubating at 37 degrees C, HA was gradually depolymerized. OTC, a representative antibiotic, is known as a photosensitizer, and phototoxic side effects relevant to radicals have been reported. However, HA depolymerization required no irradiation. As time passed, OTC solution incubated at 37 degrees C got colored reddish brown, even in the dark. With reversed-phase HPLC separation, several peaks derived from decomposed OTC appeared. One of the peaks had an absorbance in the visible range. A quantitative correlation between the discoloration and the HA depolymerization rate was obtained. On the other hand, when samples were incubated below 25 degrees C, change of color was slight, and practically no HA depolymerization was observed after up to 4 h. Oxygen depletion by nitrogen saturation or addition of mannitol also prevented the depolymerization. Under anaerobic conditions, the color of the solution did not change, whereas it turned red under aerobic conditions in the presence of mannitol. The mannitol did not inhibit the OTC decomposition, but it preserved HA from damage. On the basis of the known decomposition of OTC and the results of HPLC separation, anhydrooxytetracycline can be proposed as the derivative causing HA depolymerization.

Hot Temperature↗
PubMed2001

4-(Benzoylindolizinyl)butyric acids; novel nonsteroidal inhibitors of steroid 5alpha-reductase. III.

A novel series of indolizinebutyric acids with various benzoyl substituents was synthesized to develop nonsteroidal inhibitors of steroid 5alpha-reductase, and the structure-activity relationships in this series were studied. We previously reported the structure-activity relationships in a series of indolebutyric acids as well as the discovery of the novel nonsteroidal 5alpha-reductase inhibitor, FK143. We have now made other modifications to this compound to improve in vivo inhibitory activity. By altering the heterocyclic nucleus and changing the benzoyl substituent we have succeeded in identifying the strongly active compound, FK687, (S)-4-[1-[4-[[1-(4-isobutylphenyl)butyl]oxy]benzoyl]indolizin-3-yl]butyric acid, which displays strong in vitro inhibitory activity against the human enzyme and in vivo inhibitory activity against the castrated young rat model. This compound should be a useful agent for the treatment of benign prostatic hyperplasia.

5-alpha Reductase Inhibitors↗
PubMed2001

[Awareness of the health and defecation tendencies among college students by location of domicile].

In order to compare the food habits and defecation tendencies by region, a questionnaire survey was conducted of 1722 college women (18-20 years of age) living in Sapporo (146), Sendai (183), Osaka (1214), and Kumamoto (179). (1) When questioned about food habits, less than 58.5% of the respondents in the four groups considered their food intake to be sufficient to maintain their health. In regard to knowledge about their food intake requirements, the positive response was the highest in Sendai (85.8%), followed by Kumamoto (58.2%) and Osaka (50.9%) with the lowest in Sapporo (41.1%) (p < 0.01, among the four groups). (2) The students in Sendai, Osaka, Kumamoto and Sapporo, 96.2%, 93.5%, 92.9% and 92.5%, respectively, considered that constipation could affect their health (p < 0.05, among four groups). The percentage of those with regular bowel movements every day, tended to decrease in the order of Osaka (22.2%), Sapporo (21.2%) and Sendai (20.8%), with the lowest in Kumamoto (12.3%). Bowel movements of less than three times a week were reported by 24.7% in Sapporo, 24.0% in Sendai, 23.2% in Osaka and 22.3% in Kumamoto (p < 0.01, among the four groups). (3) Of those who defecated every day, in terms of time of day, the percentage was high between waking and after breakfast, with the highest percentage in Kumamoto (72.8%) and the lowest in Sapporo (61.2%) (p < 0.05, among the four groups). For subjects that responded that they should have a bowel movement every day, the highest percentage was in Osaka (91.0%) and the lowest was in Sapporo (83.9%) (p < 0.05, among the four groups).

Adolescent↗
PubMed2001

Granulysin: a novel antimicrobial.

Granulysin is a novel lytic molecule produced by human cytolytic T-lymphocytes (CTLs) and natural killer (NK) cells. It is active against a broad range of microbes, including Gram-positive and -negative bacteria, parasites and Mycobacterium tuberculosis. It is functionally related to other antibacterial peptides, like defensins and magainins, but is structurally distinct. It has structural similarity to porcine NK-lysin and to amoebapores made by Entamoeba histolytica. Synthetic peptides derived from granulysin have differential activity against eukaryotic cells and bacteria. Selective bactericidal peptides may have therapeutic roles as novel antibiotics.

Amino Acid Sequence↗
PubMed2001

In vitro transformation of rat renal cells by treatment with ferric nitrilotriacetate.

Administration of ferric nitrilotriacetate (Fe-NTA) in vivo causes acute renal tubular injury and finally induces renal cell carcinoma. There is accumulating evidence that these processes involve free radicals generated by Fe-NTA. To study the mechanism of renal carcinogenesis by Fe-NTA, we attempted to induce malignant transformation of primary cultured renal cells by treatment with Fe-NTA. When primary cultured renal cells (PRC) were treated continuously with Fe-NTA, all of the PRC died without transformation. On the other hand, when PRC were treated intermittently with Fe-NTA, transformed epithelial colonies were observed at 3 weeks after the first treatment. The established transformed cell line (RK523) showed drastic morphological transformation, grew in soft agar, and formed tumors when transplanted into athymic nude mice. These results indicate that the balance between cytotoxicity and mutagenecity is important for Fe-NTA induced transformation. The RK523 cell line may be a useful model for studying renal carcinogenesis in vitro.

Animals↗