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Biomedical subjects

S Saitoh

Publications and source records attributed to S Saitoh.

At least 199 records · Page 11Linked to original sources
PubMed1997

[Cranial MRI in the patients with chronic liver disease (CLD)].

We examined cranial MRI in 62 patients with CLD. Abnormal finding that high intensity area in symmetrical bilateral basal ganglia other than globus pallidum was found on both T-1 weighted images (T1WI) and fat suppression (chemical shift selective) images. This MRI finding was observed in 32 of 41 patients with cirrhosis while 1 of 21 patients with chronic hepatitis. This MRI finding was irreversible. The incidence of this MRI finding was correlated with severity of CLD and was statistically significant between in the patients with chronic hepatitis and those with cirrhosis. The contributing factors to the incidence of this MRI finding were severity of CLD and total bilirubin level by an analysis with logistic regression model. This MRI finding was detected clearer in a fat suppression imaging than in T1WI. The cause of this MRI finding was supposed not fat related substance by the finding of fat suppression imaging. This MRI finding would be useful for prediction of severity of CLD.

Adult↗
PubMed1997

[Two cases of advanced gastric cancer effectively treated with chemotherapy of 5-fluorouracil, cisplatin and cytarabine].

We reported two cases of advanced gastric cancer effectively treated with chemotherapy of 5-fluorouracil (5-FU), cisplatin (CDDP) and cytarabine (Ara-C), 5-FU (300-350 mg/body) was given by continuous intravenous infusion. Ara-C (20-40 mg/body) by continuous infusion and CDDP (15-20 mg/body) were added intravenously for 3-6 days. For case 1, epirubicin (30 mg/body) was also given on the first day of each therapy course. Case 1 was a 62-year-old female who had gastric cancer with liver metastasis, ovarian metastasis and peritonitis carcinomatosa. After 3 courses of the chemotherapy, reduction of ovarian metastasis greater than 75% was observed. The value of CA125 decreased from 6,800 U/ml to 527 U/ml and ascites disappeared. Case 2 was a 54-year-old male who had type 3 advanced gastric cancer with multiple liver metastases. He received 6 courses of the therapy. Both primary and metastatic tumors showed over 50% reduction in tumor size. These suggested that this combination therapy was effective for inoperable advanced gastric cancers.

Adenocarcinoma↗
PubMed1997

A case of membranous glomerulonephritis associated with gastric cancer.

We describe a patient with gastric cancer and membranous glomerulonephritis (MGN). The patient, a 61-year-old male, was admitted to our Hospital in May, 1996, because of proteinuria and hyperlipidemia persisting for a year. Laboratory examination filled the criteria of nephrotic syndrome and renal biopsy revealed MGN of stage II. Prednisolone therapy (40 mg/day p.o.) was started, followed by a gradual decrease in proteinuria from 4.5 g/day to 0.1 g/day. Endoscopic examination was performed because of stomach-ache revealed advanced gastric cancer of Borrmann 4. Desiring for a conservative therapy, he was discharged and moved to a hospice. In literature review, MGN is the most frequent lesion among various glomerular diseases associated with malignancy, such as the lung, stomach, and colon, particularly at an elderly ages, and sometimes antedates the detection of malignancy, as in the present case. In several cases with MGN, immune-complexes composed of tumor antigens, such as carcino-embryonic antigen, and antibodies have been reported to deposit in basement membrane of glomeruli, causing MGN. In the renal and gastric cancer tissues of the present case, the presence of three novel tumor-associated antigens, Span-1, Thomsen-Friedenreich antigen (T antigen) and F1 alpha antigen, was examined, using a immuno-peroxidase method. Although none of these three antigens were immuno-stained in the renal tissue, clinical course and literature review suggest that MGN in this patient seems to be associated with gastric cancer, which may have produced MGN-causing tumor antigens other than the three antigens. It should be emphasized that malignancy should be carefully and routinely examined in patients with MGN, particularly at elderly ages.

Glomerulonephritis, Membranous↗
PubMed1996

Identification of a novel transmembrane semaphorin expressed on lymphocytes.

Semaphorin (also known as collapsin) members are thought to be involved in axon guidance during neural network formation. Here, we report the isolation of a novel member, mouse semaphorin G (M-sema G), which encodes a semaphorin domain followed by a single putative immunoglobulin-like domain, a transmembrane domain, and a cytoplasmic domain. M-sema G is most closely related to M-sema F, which we previously reported, and semB and semC. These four members appear to constitute a transmembrane type subfamily in mouse semaphorins. In contrast to the predominant expression of M-sema F mRNAs in the nervous tissues, M-sema G mRNAs are strongly expressed in lymphoid tissues, especially in the thymus, as well as in the nervous tissues. The mRNAs are also detected in various cell lines from hematopoietic cells. By generating specific antibodies, we confirmed the strong expression of M-Sema G proteins on the surface of lymphocytes. These results provide the first evidence that semaphorin is expressed on lymphocytes and suggest that semaphorins may play an important role in the immune system, as well as in the nervous system.

Amino Acid Sequence↗
PubMed1996

Molecular epidemiology of breast cancers in northern and southern Japan: the frequency, clustering, and patterns of p53 gene mutations differ among these two low-risk populations.

Comparison of acquired mutations in the p53 tumor suppressor gene can illuminate factors contributing to carcinogenesis among cancer cohorts. Japan has an ethnically homogeneous population with a low incidence of breast cancer. Previously we reported an unusual frequency, allelic status, and clustering of mutations in breast cancers from the northern part of the main Japanese island. To extend these findings, exons 2-11 and adjacent intronic sequences were analysed in tumors of women from northern (Hokkaido) and southern (Tokushima) Japan. The frequency of breast cancers with p53 gene mutations in the Hokkaido group is the highest reported (81%) while that in Tokushima (28%) is similar to most other populations. Thirteen of the 19 mutations (68.4%) in the Hokkaido cohort were heterozygous, an unusually high frequency for p53 mutations in any tumor type. There were three missense mutations at codon 175, a known hotspot for alterations in the p53 gene, and three missense mutations at codon 179, a rare site for p53 changes. In addition, the patterns of p53 gene mutation differed between the two Japanese cohorts (P=0.04). The multiple differences in acquired p53 mutations suggest unsuspected biological differences among breast cancers in northern and southern Japan. In addition, the high frequency of p53 mutations in breast cancers from Hokkaido predicted a poorer prognosis for this population which was confirmed on examination of mortality data.

Adult↗
PubMed1996

Minimal definition of the imprinting center and fixation of chromosome 15q11-q13 epigenotype by imprinting mutations.

Patients with disorders involving imprinted genes such as Angelman syndrome (AS) and Prader-Willi syndrome (PWS) can have a mutation in the imprinting mechanism. Previously, we identified an imprinting center (IC) within chromosome 15q11-ql3 and proposed that IC mutations block resetting of the imprint, fixing on that chromosome the parental imprint (epigenotype) on which the mutation arose. We now describe four new microdeletions of the IC, the smallest (6 kb) of which currently defines the minimal region sufficient to confer an AS imprinting mutation. The AS deletions all overlap this minimal region, centromeric to the PWS microdeletions, which include the first exon of the SNRPN gene. None of five genes or transcripts in the 1.0 Mb vicinity of the IC (ZNF127, SNRPN, PAR-5, IPW, and PAR-1), each normally expressed only from the paternal allele, was expressed in cells from PWS imprinting mutation patients. In contrast, AS imprinting mutation patients show biparental expression of SNRPN and IPW but must lack expression of the putative AS gene 250-1000 kb distal of the IC. These data strongly support a model in which the paternal chromosome of these PWS patients carries an ancestral maternal epigenotype, and the maternal chromosome of these AS patients carries an ancestral paternal epigenotype. The IC therefore functions to reset the maternal and paternal imprints throughout a 2-Mb imprinted domain within human chromosome 15q11-q13 during gametogenesis.

Angelman Syndrome↗
PubMed1996

Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a signal through thymic shared antigen-1/stem cell antigen-2.

During T cell development in the thymus, the expression of thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2), a glycosylphosphatidylinositol (GPI)-anchored differentiation antigen, is developmentally regulated. The expression level of TSA-1 is the highest in most immature CD4- CD8- thymocytes, high in CD4+ CD8+ thymocytes, but barely detectable in mature CD4+ CD8- or CD4- CD8- thymocytes and peripheral T cells. We have previously shown that surface TSA-1 expression in peripheral T cells is induced upon activation and that anti-TSA-1 mAb inhibits the T cell receptor (TCR) signaling pathway in activated T cells. In the present study, we have analyzed a role of TSA-1 in thymic selection events, especially in TCR-mediated apoptosis. In in vitro experiments, anti-TSA-1 blocked anti-CD3-induced cell death of T cell hybridomas. When anti-TSA-1 was injected into newborn mice in vivo together with anti-CD3 epsilon or anti-TCR-beta, TCR/CD3-mediated apoptosis of thymocytes was almost completely blocked. The blockade of apoptosis was defined by the inhibition of, first, the decrease in total number of thymocytes; second, the decrease in percentages of CD4+ CD8+ thymocytes; and third, the induction of DNA fragmentation. However, anti-TSA-1 did not block either steroid- or radiation-induced apoptosis, indicating that a signal via TSA-1 does not inhibit a common pathway of thymocyte apoptosis. Since TCR-mediated apoptosis is pivotal in thymic ontogeny, these results suggest that TSA-1/Sca-2 is an important cell surface molecule regulating the fate of a developing T cell.

Animals↗
PubMed1996

Cyclin-dependent kinase-2 (Cdk2) forms an inactive complex with cyclin D1 since Cdk2 associated with cyclin D1 is not phosphorylated by Cdk7-cyclin-H.

Cyclin-dependent kinases (Cdks) form complexes with cyclins, and as a consequence they generally express kinase activities. One of these Cdks, Cdk2, is known to bind with cyclins A and E, and plays an important role in the progression of the cell cycle via phosphorylation of target proteins such as the product of the retinoblastoma tumor-suppressor gene (pRB). It has been suggested that Cdk2 bound with cyclin D1 and Cdk2-cyclin-D1 complex show neither H1 histone nor pRB kinase activity. However, it is not clear whether Cdk2-cyclin-D1 has unknown targets and why Cdk2 is not activated by binding with cyclin D1. We investigated these questions using Cdk, cyclin and Cdk-cyclin complexes produced in a baculovirus expression system. Cdk2 formed a complex with cyclin D1 in this system. After extensive purification, Cdk2 was still bound to cyclin D1. The Cdk2-cyclin-D1 complex did not phosphorylate any tested substrates, such as H1 histone, pRB, SV40 large T antigen, p53, E2F-1 or a preparation of nuclear proteins from HeLa cells; in contrast, Cdk2-cyclin-E and Cdk2-cyclin-A phosphorylated these proteins. Moreover, the Cdk2-cyclin-D1 complex was not activated by incubation with Cdk4 or cyclin E. Thus, Cdk2 and cyclin D1 formed a stable complex that was not activated. In order to determine why Cdk2-cyclin-D1 lacks kinase activity, we investigated the phosphorylation of Cdk2. Under-shifted Cdk2, the active form of Cdk2, was not detected in the Cdk2-cyclin-D1 complex in the baculovirus system. In human WI-38 cells, cyclin D1 began to form a complex with Cdk2 as well as with Cdk4 from the mid-G1 phase of the cell cycle. The Cdk2 bound to cyclin D1 in human cells was also the inactive form that was slowly migrated. Moreover, we found that Cdk2 bound to cyclin D1 was not phosphorylated by Cdk7-cyclin-H, while Cdk2 bound to cyclin E, as well as free Cdk2, was was phosphorylated by Cdk7-cyclin-H. Additionally, Cdk2 phosphorylated by Cdk7-cyclin-H did not bind to cyclin D1. These results strongly suggest that Cdk2 forms a stable complex with cyclin D1 but is not activated because the Cdk2 molecule in the complex is not phosphorylated by Cdk7-cyclin-H and the phosphorylated Cdk2, an active form, does not bind to cyclin D1.

Animals↗
PubMed1996

Peroneal osteocutaneous flap raised on reconstructed popliteal artery for delayed union following open tibial fractures.

Two cases of delayed union following type IIIC open tibial fracture were treated by a pedicled peroneal osteocutaneous flap raised on reconstructed popliteal vessels. Dissection of the peroneal vessels from the already traumatized extremity was tedious, but this technique provided a reliable vascularized skin and bone graft that was indispensable for the fracture healing. Peroneal osteocutaneous flaps raised on the reconstructed popliteal artery have not been reported to date; they appear to be a good alternative to free osteocutaneous flaps for non-union of the proximal tibia.

Adult↗
PubMed1996

Age-related changes in the localization of glycosaminoglycans in condylar cartilage of the mandible in rats.

There is little information available regarding the morphological and biomolecular characteristics of mandibular condylar cartilage. The purpose of this study was to determine the age-related changes in the morphology and immunolocalization of glycosaminoglycans (GAGs) in mandibular condyles. The mandibular condylar cartilages from 4-, 8-, 16-, 32-, and 64-week-old Wistar male rats were examined to verify the localization of chondroitin-4-sulfate (Ch-4S), chondroitin-6-sulfate (Ch-6S) and keratan sulfate (KS) using an indirect immunofluorescent technique with three monoclonal antibodies for glycosaminoglycans, 2-B-6, 3-B-3 and 5-D-4, respectively. Morphologically, the condylar cartilage was a growth cartilage during growing periods, began to differentiate into articular cartilage from the central area of 16-week-old condyles, and became mature articular cartilage at 32 weeks of age. A regional difference was found in the morphological features and distribution of GAGs between the anterior, central, postero-superior and posterior areas of the condyles at each age. The immunohistochemical localizations of these three glycosaminoglycans showed age-related, morphology-dependent changes, from growth cartilage to articular cartilage-like cartilage. Immunoreactions for all of the antibodies decreased progressively with age in the interterritorial matrix, while the pericellular and territorial matrix in the condylar cartilage of the mandible maintained relatively higher immunoreactivity. In conclusion, age-related and regional differences in the localization of glycosaminoglycans Ch-4S, Ch-6S, and KS were found in the mandibular condyles in rats, and these changes are believed to be related to functional and developmental requirements.

Aging↗
PubMed1996

Effects of short-term dietary change from high fat to high carbohydrate diets on the storage and utilization of glycogen and triacylglycerol in untrained rats.

The effects of short-term diet change from high fat (F) to high carbohydrate (C) (or vice versa) on the storage and utilization of glycogen and triacylglycerol (TG) in muscle and liver were studied in untrained rats. Rats were fed on an F or C diet for 28 days. For an additional 3 days, half of the rats in both F and C groups were fed the same diets as before (F-F and C-C) and the other half of the rats were switched to the counterpart diets (F-C and C-F). On the final day of the experiment, half of the rats in each diet group were exercised by swimming for 1.5 h and the other half were rested. Short-term diet change from F to C diets increased, but the change from C to F diets decreased, glycogen stores of soleus and plantaris muscles and liver, resulting in no difference in glycogen stores between F-C and C-C, and between F-F and C-F. The dietary change also had an affect on TG stores of red gastrocnemius muscle and liver-however, muscle TG stores were still higher in F-C than in C-C and C-F, and there were no differences in liver TG stores between F-C and C-F. Exercise decreased muscle glycogen contents markedly in F-C and C-C, whereas, it decreased muscle TG concentrations in F-F and C-F. Liver glycogen depletion was lower in F-C than in other groups. Lipolytic activities of epididymal adipose tissue at rest and postexercise were no differences between F-F and F-C, and were higher in F-C than in C-C and C-F. beta-adrenergic receptor binding was determined with [125I] iodocyanopindolol, and maximal numbers of beta-adrenergic receptor of plasma membrane from perirenal adipose tissue were approximately 170%-200% higher in F-C than in other groups at rest and postexercise. These results suggested that short-term C diet fed rats adapted to F diet enhanced not only glycogen stores of muscle and liver but also did not decrease lipolytic activity of adipose tissue with increased beta-adrenergic receptor density, resulting in the preservation of energy reserves (glycogen and TG) of muscle at rest, and liver glycogen sparing during exercise.

Adipose Tissue↗
PubMed1996

IgA nephropathy presenting clinicopathological features of acute post-streptococcal glomerulonephritis.

UNLABELLED: A 5-year-old Japanese girl was affected with acute nephritis. The patient had hypo-complementaemia and an elevation of anti-streptolysin O with positive throat culture of Group A streptococci. Four weeks after onset of the disease, serum complement level returned to normal, but proteinuria increased into the nephrotic range with a deterioration in renal function. Four weeks after onset, light microscopy of a renal biopsy showed diffuse endocapillary proliferation, and immunofluoroscopy revealed predominant IgA deposition in the mesangium. Electron microscopy showed electron dense deposits in the mesangial and subendothelial area, but subepithelial deposits were not found in the glomeruli. Histological diagnosis was IgA nephropathy, while her clinico-serological features were typical of acute post-streptococcal glomerulonephritis. CONCLUSION: These results suggest that in some patients, IgA nephropathy may be triggered by streptococcal infection and misdiagnosed as acute post-streptococcal glomerulonephritis if renal histological examinations are not done.

Acute Disease↗
PubMed1996

Relationship between pretreatment viremia level and response to interferon-alpha therapy in chronic hepatitis C differs in viral type 1 and 2 infections.

To determine the contribution of virus-related factors to long-term remission of chronic hepatitis C infection, we analyzed viral type and viremia level in 185 patients who had undergone a six-month course of interferon-alpha therapy. These virus-related factors were measured by an enzyme-linked immunosorbent assay with use of viral type-specific antigens and the branched DNA (bDNA) signal amplification assay, respectively. Sustained and long-term sustained responses were achieved in 55% and 50% of the patients, respectively. Transient or no responses were observed in 30% and 15% of the patients, respectively. Thirty-five percent of viral type 1 patients and 82% of viral type 2 patients had long-term sustained responses. Forty-two percent of bDNA-positive and 71% of bDNA-negative patients experienced long-term sustained responses. On multivariate analysis, viral type, Knodell's intralobular score, and viremia level were strong independent predictors of long-term sustained response (P < 0.0001, = 0.0060, and 0.037, respectively). Viremia level, however, was a significant predictor only in viral type 1, not type 2, patients. The relation between pretreatment viremia level and response to interferon-alpha therapy in chronic hepatitis C differs in viral type 1 and 2 infections.

Chronic Disease↗
PubMed1996

A randomized, double-blind, controlled trial of natural interferon-beta therapy for e-antigen-negative chronic hepatitis B patients with abnormal transaminase levels.

Intermittent interferon (IFN) therapy appears to be effective for patients with e-antigen-negative chronic hepatitis B who exhibit abnormal fluctuations of alanine aminotransferase (ALT) levels and histological evidence of disease progression. To determine the optimal dose of IFN in such patients, we studied the effects of natural IFN-beta in a prospective, randomized, double-blind, controlled trial in 36 patients with e-antigen-negative chronic hepatitis B who repeatedly demonstrated abnormal fluctuations in ALT levels. Thirty-six patients were randomly assigned to three groups, receiving doses of: 0.3 MIU IFN (group 1; n = 12), 1 MIU (group 2; n = 12), or 3 MIU (group 3; n = 12), administered twice per week for 24 weeks. Patients were regarded as responders if ALT levels remained within the normal range and HBV-DNA tested negative for 6 months after the initiation of the therapy. According to this criterion, treatment was effective in 16.7% of the patients (2/12) in group 1, 33.3% (4/12) in group 2, and 75% (9/12) in group 3, the efficacy rate in group 3 being significantly higher than that in the other two groups. However, in 12 of the 15 responders, (80%) ALT levels were frequently elevated again within 3 years of the termination of IFN therapy. Although IFN was effective in controlling the manifestations of hepatitis in terms of e-antigen-negative patients who exhibited abnormal fluctuations in ALT, it appears that continuous treatment with intermittent high-dose IFN is necessary to maintain ALT levels within the normal range.

Adult↗
PubMed1996

Ischemic colitis during interferon-alpha treatment for chronic active hepatitis C.

Between 1991 and 1994, at Hoshigaoka Koseinenkin Hospital, we treated 280 patients with chronic hepatitis C with interferon (IFN), and ischemic colitis occurred in two patients (0.7%) during the treatment. Melena appeared in case 1 in the 2nd month after the initiation of IFN-alpha treatment, and in case 2 in the 6th month. In both patients, longitudinal ulcerations in the descending colon were revealed by urgent colonoscopy, and these resolved within 2 weeks after discontinuation of the IFN treatment. It appears that ischemic colitis was associated with the IFN treatment, suggesting that attention should be paid to this possible complication.

Aged↗
PubMed1996

Hepatitis C virus subtype 3b infection in a hospital in Japan: epidemiological study.

To elucidate the epidemiology of infection with hepatitis C virus (HCV) subtype 3b (a rare subtype thought to have originated in Southeast Asia) in Japan, we examined the genotypic subtype in 1397 patients with HCV-related chronic liver diseases. Of 1330 patients with identified HCV RNA genotypes. 960 had subtype 1b, 243 had subtype 2a, 97 had subtype 2b, 14 (1.1%) had subtype 3b, and 16 had other types of HCV or mixed subtypes. The age, gender, and severity of liver disease in patients with HCV subtype 3b did not differ from these features in patients with other subtypes. Eleven of the 14 patients with the 3b subtype had once worked at Company A in Tokyo, Japan. Multivariate logistic analysis showed that working history at that company was independently associated with the incidence of the subtype; the risk ratio was 207.2 (P < 0.0001). All 11 patients from Company A had received medical services, between 1953 and 1981, at Clinic C, which undertook medical care of the company staff. All 11 patients had received repeated intramuscular or intravenous injections for treatment of various diseases or for preventive vaccination for contagious diseases. The rare HCV subtype 3b, appeared to have been transmitted among the employees of a company through the performance of certain medical practices.

Adult↗
PubMed1996

Effects of synchronized retroperfusion on the coronary arterial pressure-flow relationship.

OBJECTIVE: We compared the effects of diastolic coronary sinus pressure elevation due to synchronized retroperfusion (SRP) with systolic coronary sinus pressure elevation due to coronary sinus occlusion on the coronary pressure-flow relationship under similar mean coronary sinus pressure values. METHODS: Using isolated, perfused canine hearts, coronary perfusion of the left anterior descending artery was reduced gradually, setting the mean coronary sinus pressure to 14.2 +/- 5.7 mmHg (mean +/- s.d.) under control conditions, 30.3 +/- 4.9 mmHg under SRP with lower retrograde perfusion flow [SRP(L)], 30.7 +/- 4.6 mmHg under coronary sinus partial occlusion [CSPO], 51.9 +/- 7.9 mmHg under SRP with higher retrograde perfusion flow [SRP(H)] and 49.0 +/- 7.9 mmHg under coronary sinus complete occlusion [CSCO]. Zero-flow pressure and the slopes of pressure-flow relationship were determined in each condition. RESULTS: The mean values of the slopes did not significantly differ among the interventions. The mean control value of zero-flow pressure was 17.4 +/- 4.3 mmHg. Zero-flow pressure of SRP(L) was 20.0 +/- 3.5 mmHg, which was not a significant increase, whilst zero-flow pressure of CSPO was 22.9 +/- 3.4 mmHg, a significant increase compared with control (P < 0.05). Zero-flow pressure of SRP(H) and CSCO was 26.0 +/- 4.5 and 31.3 +/- 6.7 mmHg, respectively, and both were significantly higher than control (P < 0.01). Zero-flow pressure of SRP(H) was, however, significantly lower than CSCO (P < 0.05). CONCLUSIONS: SRP, which causes diastolic coronary sinus pressure elevation, does not greatly affect coronary arterial inflow, compared with coronary sinus occlusion which causes systolic coronary sinus pressure elevation. These results suggest that the blood volume contained in the heart during systole plays a role in determining coronary inflow. Therefore, SRP intervention, which does not interfere with venous outflow during systole, may ameliorate injured myocardium during ischaemia without seriously affecting coronary inflow supply.

Animals↗