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Biomedical subjects

S Saitoh

Publications and source records attributed to S Saitoh.

At least 271 records · Page 15Linked to original sources

Imaging diagnosis of small hepatocellular carcinoma.

To elucidate the detectability of small hepatocellular carcinoma by various imaging modalities, we performed digital subtraction angiography, computed tomographic arterioportography and carbon dioxide-enhanced ultrasonography. Of 76 patients with a small hepatocellular carcinoma of 2 cm or less in maximum diameter, 61 underwent digital subtraction angiography, computed tomographic arterioportography and enhanced ultrasonography at the same time. Concerning the 61 patients undergoing all the procedures, the characteristics of hepatocellular carcinoma were found in 57.4% (35 of 61) by digital subtraction angiography, 75.4% (46 of 61) by computed tomographic arterioportography and 72.1% (44 of 61) by enhanced ultrasonography. Among them, four hepatocellular carcinomas were detected only by enhanced ultrasonography, three were diagnosed only by computed tomographic arterioportography and two were diagnosed by both of them. Except for six hemangioma nodules that were easily diagnosed only with angiography, four of 55 benign hepatic nodules (7.3%) showed false-positive findings suggestive of hepatocellular carcinoma with either computed tomographic arterioportography or enhanced ultrasonography. In conclusion, computed tomographic arterioportography and enhanced ultrasonography could complementarily detect a small hepatocellular carcinoma more sensitively than digital subtraction angiography.

Adult↗

Activation-induced expression of thymic shared antigen-1 on T lymphocytes and its inhibitory role for TCR-mediated IL-2 production.

We have produced a hamster mAb, PRST1, which reacts with thymic shared Ag-1 (TSA-1), a product of the Ly6 gene family. By cross-blocking experiments, we found that TSA-1 is identical to stem cell Ag-2 (Sca-2). Using PRST1, the changes of TSA-1/Sca-2 expression on mature T cells during the activation process were analyzed. Although freshly isolated T cells did not express detectable TSA-1 on their cell surface, in vitro stimulation of T cells with concanavalin A induced a marked increase of surface TSA-1 expression. The increased expression of TSA-1 on T cells was detected from 12 h after stimulation and was associated with the increase of TSA-1 mRNA. In vivo injection of mice with staphylococcal enterotoxin B (SEB) resulted in the enhanced TSA-1 expression in splenic V beta 8+ T cells. This antigen-specific induction of TSA-1 expression in vivo preceded a detectable increase in numbers of V beta 8- T cells after SEB injection. Functionally, whereas anti-TSA-1 mAb was not mitogenic to T cells, it inhibited anti-CD3-induced IL-2 production by T cell hybridomas. These results indicate that TSA-1/Sca-2 is a unique marker for T cell activation and a signal through this molecule may have a negative feedback role to limit IL-2 production from activated T cells stimulated through the TCR.

Animals↗

Nucleotide sequence of hepatitis C virus (type 3b) isolated from a Japanese patient with chronic hepatitis C.

The genomic sequences of many hepatitis C virus (HCV) isolates have been reported and a variety of virus genotypes have been classified based on homology in the conserved regions. We have previously identified five distinct genotypes (1a, 1b, 2a, 2b and 3b) in Japanese patients with chronic HCV infection by comparing the sequences of the NS5 region. The complete nucleotide sequence for five genotypes (1a, 1b, 1c, 2a and 2b) have already been reported and we report here the complete nucleotide sequence of genotype 3b. The isolate (HCV Tr) was 9439 nucleotides long, excluding the poly(U) tract at its 3' end, and encodes a single long open reading frame of 3023 amino acids. Total nucleotide sequence homologies were 68.4 to 68.7%, 68.3 to 69.0%, 67.2%, 65.8% and 65.6% compared with type 1a, 1b, 1c, 2a and 2b genomes, respectively. The amino acid sequences of these five genotypes were highly homologous in the core, NS3 and NS5B regions, but the E2/NS1 region, which contains hypervariable regions 1 and 2, and the NS5A region were poorly conserved. Although it was possible to detect antibody against the relatively homologous core and NS3 regions by ELISA, the presence of divergent protein structures must be taken into account in the development of a vaccine.

Amino Acid Sequence↗

Small hepatocellular carcinoma: evaluation of portal blood flow with CT during arterial portography performed with balloon occlusion of the hepatic artery.

PURPOSE: To evaluate portal blood flow in small hepatocellular carcinomas (HCCs) by means of computed tomography during arterial portography (CTAP) and CTAP with hepatic arterial obstruction (CTP-HAO) achieved by means of balloon occlusion. MATERIALS AND METHODS: Thirteen patients with small HCC (< 20 mm in diameter) underwent CTAP, CTP-HAO, carbon dioxide-enhanced ultrasound (CEUS), and digital subtraction angiography (DSA). The imaging findings were correlated with histologic features. RESULTS: The first group of patients (n = 3) had tumors with portal blood flow at both CTAP and CTP-HAO and no hypervascularity at CEUS. The second group (n = 3) had tumors with portal blood flow at CTP-HAO but not at CTAP and hypervascularity at CEUS only. The third group (n = 7) had tumors without portal blood flow at CTAP or CTP-HAO and hypervascularity at DSA and CEUS. The first and second groups had well-differentiated HCCs; six of seven patients in the third group had moderately differentiated HCCs. CONCLUSION: Lack of portal blood flow was reversible in well-differentiated HCCs but irreversible in the other tumors.

Carcinoma, Hepatocellular↗

Effects of a metalloendopeptidase-24.15. Inhibitor on renal hemodynamics and function in rats.

N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB), an active-site-directed inhibitor of metalloendopeptidase-24.15, has been shown to lower blood pressure, increase cardiac output and renal blood flow, and potentiate the intravenous bradykinin-induced vasodepressor response. Because in vivo cFP-AAF-pAB can be converted to N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala (a compound with angiotensin converting enzyme inhibitory activity) by metalloendopeptidase-24.11, it is possible that some of its effects are due to angiotensin converting enzyme inhibition. In the present study, we questioned (1) whether cFP-AAF-pAB inhibits angiotensin converting enzyme in vivo and (2) whether cFP-AAF-pAB has renal effects that are independent of its conversion to an angiotensin converting enzyme inhibitor. cFP-AAF-pAB alone (3 mumol in 300 microL per rat) almost abolished the blood pressure response to angiotensin I, suggesting that in vivo it inhibits angiotensin converting enzyme. In rats pretreated with a high dose of enalaprilat (1 mg/kg), cFP-AAF-pAB had no further effect on blood pressure, renal blood flow, or potentiation of the vasodepressor response to bradykinin but still increased glomerular filtration rate by 44 +/- 9% (P < .01); urine volume increased by 118 +/- 10% (P < .001), urinary sodium excretion by 230 +/- 31% (P < .001), urinary potassium excretion by 68 +/- 14% (P < .01), and urinary cyclic GMP by 55 +/- 18% (P < .01). All of these changes were significant compared with enalaprilat/vehicle-treated rats. Fractional excretion of sodium and potassium did not differ from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

Management of acute leukemia during pregnancy: from the results of a nationwide questionnaire survey and literature survey.

In March, 1993, a questionnaire was sent to 362 gynecological and obstetric offices of national, prefectural and municipal hospitals and private university hospitals with 250 beds or more. Answers were collected from 260 institutions. Thus, this study analyzed 39 patients with acute leukemia during pregnancy collected by the questionnaires survey and 64 cases reported in the Japanese literatures during 1975-1993 (total 103 patients). The weeks of pregnancy were defined as the 1st (< 15th week), 2nd (16th-27th week), and 3rd (> 28th week) trimesters. The time of diagnosis of leukemia during pregnancy changed from 25% in the 2nd trimester and 62% in the 3rd trimester during 1975-1984 to 39% and 48% after 1985, respectively. After 1985, the remission rate was 72% in the questionnaire group and 75% in the group from literatures. There was no statistical difference. The 50% survival period was 12 months in the group during 1975-1984, but 25 months in the group after 1985. The survival was significantly longer in the patients whose induction therapy was started before delivery than in those treated after delivery. The results suggest that the treatment for acute leukemia during pregnancy should be initiated as soon as possible after the diagnosis of leukemia, with carefully selected regimens. It is important that the time of delivery should be selected considering the maternal and fetal conditions after consultation with an obstetrician.

Adult↗

[Combination therapy of high energy under water shock waves and anticancer drugs for subcutaneous murine bladder cancer (MBT-2)].

The effect in combination therapy of high energy under water shock waves (HESW) and anticancer drugs for subcutaneous murine bladder cancer (MBT-2) in C3H/He mice was examined. HESW were generated by piezoceramics and directed to the subcutaneous tumor under ultrasonographic guidance. The subcutaneous tumor was exposed to HESW alone (100 MPa, 1000 shots, 3 shots/sec) or in combination with pirarubicin (THP, 5 mg/kg, i.p.) or carboplatin (CBDCA, 40 mg/kg, i.p.). Remarkable bleeding in the tumor was seen immediately after the exposure of HESW, destroyed cancer cells appeared after one day and wider and clearly bordered tumor necrosis was observed after three days. In the HESW alone therapy, tumor growth of smaller tumors (< 10 mm3, n = 8) were suppressed more than that of larger tumors (10-35 mm3, n = 11). Tumor growth ratio on the 14th day (TGR 14) (tumor volume on the 14th day/tumor volume on the 1st day) was examined in larger tumors. TGR 14 were 152.2 +/- 146.6 (mean +/- S.D.) in the control (n = 20), 116.3 +/- 98.9 in HESW alone (n = 11), 75.5 +/- 110.7 in THP alone (n = 8), 90.7 +/- 61.6 in CBDCA alone (n = 6), 75.8 +/- 72.2 in THP + HESW (n = 9), 3.2 +/- 4.5 in CBDCA + HESW (n = 8) and 0.8 +/- 1.3 in CBDCA + HESW 2 cycles (n = 9). Evident suppression on tumor growth was more often seen in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.01). The cumulative survival rates were higher in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.05). Tumor metastasis was seen only in the lungs of the dead mice after 19 days. Lung metastases were seen in 1/6 in the control, 0/5 in HESW alone, 1/5 in CBDCA alone, 0/6 in CBDCA + HESW and 1/5 in CBDCA + HESW 2 cycles therapy, respectively.

Animals↗

[Trans-urethral whole layer core biopsy of invasive bladder tumor].

We have developed a percutaneous whole layer core biopsy (WLCB) of bladder tumor and applied it successfully to stage invasive bladder tumor since April, 1985. We report here a modified method, trans-urethral WLCB (TU-WLCB) and present its clinical results. The patient was placed in the lithotomy position under caudal anesthesia, and a 20 F rigid nephroscope was introduced transurethrally. A newly developed 18-gauge (1.2 mm), 350 mm-long biopsy needle (Crown Core Cut Biopsy Needle) was advanced to the tumor through the nephroscope. A longitudinal transabdominal US was used to measure the distance between the needle tip and the outer layer of the bladder tumor. Because the needle advances 2.5 cm when fired by spring-loaded BIP Biopsy Gun (BIP, Germany), biopsy is performed by advancing the needle tip until the outer layer of tumor is slightly pierced under US guidance. Specimens of all 11 trans-urethral WLCB cases included the muscle layer and adipose tissue, and pathological staging were possible. TU-WLCB could be applied safely to tumors located at posterior wall and covered with the peritoneum. Serious complications were not observed so far. Thus, TU-WLCB may become a reliable technique to stage and evaluate neoadjuvant therapy for invasive bladder cancer.

Adult↗

Histamine release from rabbit platelets by platelet-activating factor (PAF).

In this study, we examined firstly whether PAF could activate washed platelets of rabbits and release ATP from the platelets, secondly whether activated platelets could release histamine, and thirdly whether certain antagonists of PAF could inhibit the release of histamine from platelets. The results obtained in these experiments may be summarized as follows. 1) Release of ATP was increased with enhanced platelet aggregation by PAF. At 3.4 x 10(-7) M of PAF, the maximal aggregation rate of platelets was about 70% and the concentration of released ATP was 1.6 x 10(-5) M. 2) After aggregated platelets induced by PAF had been sonicated and centrifuged, the resultant supernatant could cause contraction of the guinea pig ileum. This contraction was inhibited by the antihistaminic agents, cimetidine and pyrilamine. Furthermore, the histamine content of the supernatant was about 3.7 micrograms/ml (platelet count, 30 x 10(4)/microliter). 3) At 10(-5) M of CV-3988, the inhibitory ratio of PAF-induced aggregation was 35% and that of histamine release was 50%. On the other hand, at 5 x 10(-7) M of CV-6209, the inhibitory ratio of PAF-induced aggregation was 35% and that of histamine release was about 30%. From the above results, it was clear that PAF-activated platelets could release histamine. In addition, it is suggested that a direct relationship between PAF and platelets may exist in the process of allergic reactions, and histamine from PAF-activated platelets may modify allergic reactions.

Adenosine Triphosphate↗

p53 gene mutations in breast cancers in midwestern US women: null as well as missense-type mutations are associated with poor prognosis.

We determined the pattern of mutations in exons 2-11 and adjacent intronic regions in breast cancers from Midwestern US white women. Twenty-one mutations were detected in 53 tumors (39.6%). Comparisons of the pattern of mutations within exons 5-9 showed that the frequency of missense mutations (44%) was lower in breast cancers of US Midwestern women than in most tumor types including breast cancers in other populations. Compared to breast cancers reported in a Scottish population, US women had a high frequency of G:C-->T:A transversions (P = 0.046). These findings suggest that environmental or endogenous factors contribute to p53 mutagenesis in mammary tissue to different extents among different populations. With a median follow-up of 19 months, the presence of a mutation was associated with shorter time to disease recurrence (P = 0.05) and shorter survival (P = 0.003). Putative dominant negative missense-type mutations (missense and in-frame microdeletions; P = 0.001) and null mutations (hemizygous nonsense and frameshift mutations; P = 0.007) were equally ominous. Thus, tumors with missense p53 mutations resulting in over-expression of a dysfunctional but otherwise intact protein have a clinical outcome similar to tumors with null mutations resulting in a truncated or garbled protein.

Adult↗

Factors predictive of response to interferon-alpha therapy in hepatitis C virus infection.

To determine the patient-dependent and virus-related factors that may predict sustained response to interferon-alpha therapy, we prospectively evaluated 60 consecutive patients with chronic hepatitis C who received a standardized treatment schedule of interferon-alpha. Twenty-eight patients achieved a long-term sustained remission, 14 patients had temporary responses during treatment but relapsed after completing it and 14 patients did not respond. Four patients dropped out because of severe side effects and were excluded from evaluation of efficacy. Twenty-one variables were chosen as possible predictors of sustained response and were analyzed by means of multivariate analysis. Variables related to the hepatitis C virus included genotype and concentration in serum before treatment. The former was determined by means of the polymerase chain reaction with genotype-specific primers for genotypes PT, K1, K2a and K2b, which were deduced from nonstructural region 5 of the hepatitis C virus genome. The latter was measured with a competitive polymerase chain reaction technique. Three variables were statistically significant (p < 0.05) on univariate analysis: viral genotype, pretreatment level of viremia and Knodell's fibrosis score. In multivariate analysis viral genotype and Knodell's fibrosis score were correlated independently with a sustained response (p < 0.05 for both). Incidence of sustained response was 40% and 91% in patients with genotypes K1 and K2a, respectively. We conclude that with the treatment schedule used, viral genotype was the most useful predictor of a sustained response to treatment with interferon-alpha.

Adult↗

Myristoylation of hippocalcin is linked to its calcium-dependent membrane association properties.

Hippocalcin, a recently identified Ca(2+)-binding protein of the recoverin family exclusively expressed in the hippocampus, has a primary structure containing three putative Ca(2+)-binding sites (EF-hands) and a possible NH2-terminal myristoylation site. 45Ca blots demonstrated that every three EF-hand domains, expressed as fusion proteins in Escherichia coli, bind Ca2+, indicating that hippocalcin binds 3 mol of Ca2+/mol of protein. To determine whether hippocalcin is myristoylated, hippocalcin mRNA was translated in vitro in the presence of [3H]myristic acid. 3H label was resistant to hydroxylamine treatment, and replacement of NH2-terminal glycine with alanine prevented 3H label incorporation, indicating that in vitro translated hippocalcin covalently bound [3H]myristic acid at the NH2-terminal glycine. In vitro translated hippocalcin is quantitatively myristoylated, as evidenced by an electrophoretic mobility shift of [35S]methionine-labeled protein on two-dimensional gels. Native hippocalcin comigrated precisely with the in vitro translated hippocalcin on two-dimensional gels, suggesting that native hippocalcin is myristoylated. Native and in vitro translated hippocalcins, but not non-myristoylated mutagenic (Gly1-Ala1) hippocalcin, displayed Ca(2+)-dependent membrane association, indicating that myristoylation participates in its Ca(2+)-dependent membrane association properties. In vitro translated hippocalcin bound to phospholipid vesicles somewhat, however, phospholipid association was insufficient for its membrane association properties, suggesting that the NH2-terminal myristoyl moiety on hippocalcin interacts with lipid bilayers and facilitates interaction with other membrane proteins.

Alanine↗

Distribution of hippocalcin mRNA and immunoreactivity in rat brain.

Distribution of hippocalcin in rat brain was analysed by in situ hybridization and immunohistochemical methods. Hippocalcin mRNA and immunoreactivity were expressed more intensely in the pyramidal cells of the hippocampus, intensely in the Purkinje cells of the cerebellum, moderately in the dentate granule cells and pyramidal cells of cerebral cortex layers II-VI and weakly in the large neuronal cells of the caudate-putamen. Some discrepancies in the localization of hippocalcin mRNA and immunoreactivity were noted in the mamillary nuclei, anterior part of the thalamus and the septal nuclei. In most cell types, hippocalcin immunoreactivity was localized in the cytoplasm and plasma membrane of cell bodies and dendrites.

Animals↗