Biomedical subjects

S Kawa

Publications and source records attributed to S Kawa.

At least 37 records · Page 2Linked to original sources

PubMed1998

Characteristic pancreatic duct appearance in autoimmune chronic pancreatitis: a case report and review of the Japanese literature.

We report a case demonstrating the progressive narrowing of the pancreatic duct, which is presumed to be characteristic of autoimmune pancreatitis, and we review the 37 cases of chronic pancreatitis in which autoimmunity was suggested as an etiological factor in the Japanese literature. A 55-year-old man presented with abdominal discomfort, jaundice, and diffuse swelling of the pancreas on ultrasonography. Serial endoscopic retrograde pancreatography demonstrated the progression of an irregular narrowing of the main pancreatic duct forming diffusely over the course of 2 months. Because the patient had hyperglobulinemia and tested positive for autoantibodies, he was diagnosed as a case of autoimmune chronic pancreatitis. Steroid therapy was carried out with excellent success.

Autoimmune Diseases↗

PubMed1998

A case of glycogen storage disease type Ia with multiple hepatic adenomas and G727T mutation in the glucose-6-phosphatase gene, and a comparison with other mutations previously reported.

We report a case of 23-yr-old man with glycogen storage disease (GSD) type Ia complicated by multiple hepatic adenomas. Analysis of the G-6-Pase gene using peripheral blood sample showed this patient to be homozygous for a G-to-T transversion at nucleotide 727 in exon 5. This mutation is prevalent among Japanese patients, suggesting that specific genotypes may correlate with different clinical courses or outcomes.

Adenoma↗

PubMed1997

Inhibition of chemotactic motility and trans-endothelial migration of human neutrophils by sphingosine 1-phosphate.

In previous studies, we reported that sphingosine 1-phosphate (Sph-1-P) inhibits the chemotactic motility of some cancer cell lines such as mouse melanoma cells, as well as human smooth muscle cells, at a very low concentration, as demonstrated by a transwell migration assay method (Proc. Natl. Acad. Sci. USA 89, 9698, 1992; J. Cell Biol. 130, 193, 1995). In this study, we investigated the effect of Sph-1-P on the chemotactic motility and invasiveness of human neutrophils, utilizing three different assay systems: (a) a transwell migration assay where IL-8 or fLMP was added as a chemotactic factor, (b) a phagokinetic assay with gold colloids, and (c) a trans-endothelial migration assay with human umbilical vein endothelial cells (HUVECs) plated on collagen layers. We found that among various sphingosine derivatives, Sph-1-P specifically inhibited the IL-8- or fLMP-induced chemotactic migration of neutrophils at concentrations below 1 microM. Phagokinetic activity of neutrophils was also suppressed by Sph-1-P, but more moderately than by the PKC inhibitory sphingosine analog, trimethylsphingosine. Finally, Sph-1-P inhibited trans-endothelial migration and invasiveness of neutrophils into HUVEC-covered collagen layers, whereas no effect on their adhesion to HUVECs was observed. These observations strongly suggest that Sph-1-P can act as a specific and effective motility regulator of human neutrophils, raising the possibility of future applications of Sph-1-P, or its analogs, as anti-inflammatory agents regulating invasive migration of neutrophils through endothelial layers at injured vascular sites.

Cell Adhesion↗

PubMed1997

Arotinoid mofarotene (RO40-8757) up-regulates p21 and p27 during growth inhibition of pancreatic cancer cell lines.

Effective chemotherapy for pancreatic cancer is urgently needed. The anti-proliferative activity of a new retinoid, mofarotene (RO40-8757), was compared with that of other retinoids, such as all trans-retinoic acid, 13-cis retinoic acid and 9-cis retinoic acid, on 9 pancreatic cancer cell lines in relation to the effects on various cell cycle-regulating factors. After treatment with each retinoid, anti-proliferative effect was determined by the MTT method and expression of cell cycle-regulating factors, such as cyclins (D1, E and A), cyclin-dependent kinases (2 and 4), cyclin-dependent kinase inhibitors (p21 and p27) and retinoblastoma protein, was analyzed by Western blotting. Mofarotene showed half-maximal inhibition of cell proliferation at concentrations between 0.14 x 10(-6) and 3.8 x 10(-6) mol/l with little cytotoxicity. In contrast, the other retinoids did not inhibit the growth of all cell lines by over 50% compared to controls. A marked increase in the fraction of cells in G1 phase of the cell cycle was observed after mofarotene treatment; this was associated with marked up-regulation of p21/p27 and a shift of retinoblastoma protein into the hypophosphorylated form. In conclusion, mofarotene inhibits the growth of pancreatic cancer cells by inducing G1-phase cell cycle-inhibitory factors (p21, p27 and hypophosphorylated form of Rb protein) and is considered to be a useful agent for pancreatic cancer treatment.

Alitretinoin↗

PubMed1997

Growth hormone-releasing hormone (GRH)-producing pancreatic tumor with no evidence of multiple endocrine neoplasia type 1.

The characteristic features of a 48-year-old male presenting with isolated acromegaly caused by a GRH-producing pancreatic endocrine tumor bearing no relation to MEN1 was reported. The clinical features, laboratory findings, and sellar enlargement were improved after removal of the pancreatic tumor. The resected pancreatic tumor showed positive GRH immunoreactivity and contained abundant GRH mRNA. This tumor is extremely rare and to date only 10 cases have been reported. In the management of acromegaly, the measurement of GRH is recommended and the search for an ectopic source will prevent unnecessary and potentially ineffective pituitary surgery.

Acromegaly↗

PubMed1997

Vitamin D analogues up-regulate p21 and p27 during growth inhibition of pancreatic cancer cell lines.

To obtain information regarding the growth-inhibitory effect of 1,25-dihydroxyvitamin D3 and its non-calcaemic analogue 22-oxa-1,25-dihydroxyvitamin D3 on pancreatic cancer cell lines, differences in the effects of G1-phase cell cycle-regulating factors were studied in vitamin D-responsive and non-responsive cell lines. Levels of expression of cyclins (D1, E and A), cyclin-dependent kinases (2 and 4) and cyclin-dependent kinase inhibitors (p21 and p27) were analysed by Western blotting after treatment with these compounds. In the responsive cells (BxPC-3, Hs 700T and SUP-1), our observations were: (1) marked up-regulation of p21 and p27 after 24 h treatment with 10(-7) mol l(-1) 1,25-dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3; and (2) marked down-regulation of cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors after 7 days' treatment. In non-responsive cells (Hs 766T and Capan-1), no such changes were observed. In conclusion, vitamin D analogues up-regulate p21 and p27 as an early event, which in turn could block the G1/S transition and induce growth inhibition in responsive cells.

Antineoplastic Agents↗

PubMed1997

Long-term follow-up of patients with chronic pancreatitis and K-ras gene mutation detected in pancreatic juice.

BACKGROUND & AIMS: Conflicting reports have raised the question whether K-ras gene mutations in chronic pancreatitis are related to the development of pancreatic neoplasm. The aim of the present study was to clarify this issue by surveying patients with chronic pancreatitis and K-ras gene mutation over 4 years. METHODS: K-ras point mutations at codon 12 in duodenal juices obtained during exocrine function tests were examined by enriched polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequence analysis, and long-term follow-up of these patients was performed. RESULTS: K-ras gene mutation was found in 20 of 54 patients (37%) with chronic pancreatitis. The types of mutation were GAT in 7, GTT in 11, and TGT in 2 patients. Pancreatic neoplasm occurred in none of the mutation-positive patients over a mean follow-up period of 78 months. CONCLUSIONS: K-ras gene mutation in patients with chronic pencreatitis did not seem to be related to the development of pancreatic neoplasm during the follow-up period, and analysis of K-ras gene mutation seems of little use for diagnosing pancreatic neoplasm in patients with chronic pancreatitis.

Adult↗

PubMed1996

Comparative study of CA242 and CA19-9 in chronic pancreatitis.

CA242 has been proved to be useful in the diagnosis of pancreatic cancer. The aim of the present study was to clarify the mechanisms contributing to the high specificity of CA242 as compared with CA19-9 resulting from scarce serum elevation of this antigen in patients with chronic pancreatitis by correlating serum levels and endoscopic retrograde choledocho-pancreatography (ERCP) findings and by immunohistochemical analysis. Serum CA19-9 levels were significantly elevated in patients with calcification and with main pancreatic duct (MPD) stenosis or obstruction. On the other hand, serum CA242 levels showed no significant elevation in patients with such factors. Even though such pathological conditions were considered to lead to the stagnation of pancreatic juice, serum CA242 levels seemed to be less affected than serum CA19-9 levels. Immunohistochemical studies of chronic pancreatitis tissues revealed that CA242 was expressed less frequently and less intensely than CA19-9, and the difference in expression was more prominent in the centroacinar cells and terminal ductules. From the results of the present study, it is conceivable that CA242 is less influenced by the stagnation of the pancreatic juice than CA19-9 because of the low levels of expression in ductal systems, which results in the release of this antigen into the circulation in lower amounts than that of CA19-9.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1996

Inhibitory effect of 220-oxa-1,25-dihydroxyvitamin D3 on the proliferation of pancreatic cancer cell lines.

BACKGROUND & AIMS: Effective chemotherapy for pancreatic cancer is urgently needed. The aim of this study was to compare the anti-proliferative activity of a new vitamin D3 analogue, 22-oxa-1,25-dihydroxyvitamin D3 (22-oxa-calcitriol), on pancreatic cancer cells lines with that of 1,25-dihydroxyvitamin D3 (calcitriol) with analysis of vitamin D receptor status. METHODS: Antiproliferative effects of both agents were compared using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method and by measuring the tumor size of xenograft inoculated into athymic mice. Vitamin D receptor contents by Scatchard analysis and mutational analysis of receptor complementary DNA were performed. RESULTS: In vitro, 22-oxa-calcitriol and calcitriol markedly inhibited the proliferation (3 of 9 cell lines) and caused a G1 phase cell cycle arrest by appearance of numerous domes. In vivo, 22-oxa-calcitriol inhibited the growth of BxPC-3 xenografts more significantly than calcitriol without including hypercalcemia. Hs 766T, showing no response to either agent, had the second highest receptor contents with no abnormalities in its primary structure deduced by receptor complementary DNA. CONCLUSIONS: 22-oxa-calcitriol may provide a more useful tool for the chemotherapy of pancreatic cancer than calcitriol. Also, the susceptibility of the cell lines to both agents is not well determined by evaluating either the contents or the mutation of vitamin D receptor.

Animals↗

PubMed1996

The relationship between drinking status and serial changes of pancreatographic findings in patients with suspected early chronic alcoholic pancreatitis.

Twenty-two patients (mean age, 48.5 years) suspected of early chronic alcoholic pancreatitis, who had ductal changes mainly in the side branches, were followed by serial endoscopic retrograde pancreatography (ERP). Follow-up ranged from 1.1 to 11.9 years (mean, 5.4). Serial ERP revealed deterioration in six patients (27%), five of whom had outflow disturbance of the main pancreatic duct. On the other hand, five patients presented slight progressive changes restricted to the side branches and the remaining 11 patients showed no change. None of the 12 patients who abstained from drinking showed a deterioration of their pancreatogram. The deterioration of clinical symptoms was less frequently seen in patients with abstinence (5/12) than in those who continued drinking (10/10). This study suggests that a ductal abnormality mainly in the side branches may be an early sign of chronic alcoholic pancreatitis. Outflow disturbance of the main pancreatic duct might play an important role in the progression of the pancreatogram to an advanced stage. Abstinence is associated with a high probability of stabilization of both clinical symptoms and ductal changes.

Abdominal Pain↗

PubMed1996

Autoimmune chronic pancreatitis simulating pancreatic lymphoma.

A 51-yr-old man, who presented with diabetes mellitus, abdominal pain, inguinal lymphadenopathy, and diffuse enlargement of the whole pancreas on ultrasonography, was at first thought to have pancreatic lymphoma. Chemotherapy including steroid was carried out successfully, although the definitive diagnosis of lymphoma was not made. However, on follow-up, we realized that both laboratory findings, such as hyperglobulinemia and autoantibody-positive results, and radiographic features in this case were very similar to those of a case of autoimmune pancreatitis recently reported by Yoshida et al. (Dig Dis Sci 1995;40:1561-8). When the disease recurred, therefore, treatment with steroid alone was performed with an excellent result. We report a case of autoimmune pancreatitis simulating primary pancreatic lymphoma.

Autoimmune Diseases↗

PubMed1995

[Multiple endocrine neoplasia type I].

Multiple endocrine neoplasia type 1 (MEN1) is characterized by the combined occurrence of primary hyperparathyroidism, pancreatic endocrine tumors, and neoplasms of the anterior pituitary gland. The disease is inherited as an autosomal dominant disorder with a high penetrance. Although many investigators have localized the causative genes to chromosome 11q3 by linkage analysis, the MEN1 gene remains unidentified. The use of molecular genetic markers in family linkage studies, however, have made it possible to identify gene carriers. Repetitive screening combined with the assignment of gene-carrier status will provide possibilities for therapeutic or prophylactic intervention earlier in the development of each of the manifestations of this syndrome, such as gastrointestinal bleeding secondary to ulcers or malignant transformation.

DNA↗

PubMed1994

Liposomal N,N,N-trimethylsphingosine (TMS) as an inhibitor of B16 melanoma cell growth and metastasis with reduced toxicity and enhanced drug efficacy compared to free TMS: cell membrane signaling as a target in cancer therapy III.

We demonstrated previously that N,N,N-trimethylsphingosine (TMS) and N,N-dimethylsphingosine (DMS), but not unsubstituted sphingosine, produce significant inhibitory effects on in vivo growth of human tumor cells in nude mice (K. Endo et al., Cancer Res., 51: 1613-1618, 1991) and on metastasis of B16 melanoma cells in syngeneic mice (H. Okoshi et al., Cancer Res., 51: 6019-6024, 1991). These observations were attributed to inhibition by TMS or DMS of protein kinase C activity and tumor cell-dependent platelet activation. TMS yields a more stable aqueous solution than DMS, and its antitumor effect is more reproducible. However, dosages of both TMS and DMS required to produce significant antitumor or antimetastasis effects are high (several injections of 0.1-0.3 mg/mouse). At these dosages, TMS treatment (by tail vein injection) often produced the undesirable side effects of hemolysis and hemoglobinuria. We now report that TMS incorporated into liposomes with egg phosphatidylcholine and cholesterol had no hemolytic effect, yet was more potent than free TMS in suppressing B16 melanoma cell growth and metastasis. Biodistribution assay revealed that, compared to free TMS, liposomal TMS was accumulated in tumor tissue at higher concentrations and had longer circulation half-life. These factors could explain the higher antitumor efficacy of liposomal TMS.

Animals↗

PubMed1994

Comparative study of CA242 and CA19-9 for the diagnosis of pancreatic cancer.

A comparative study of a new tumour marker, CA242, and CA19-9 was conducted with special reference to their diagnostic usefulness in pancreatic cancer. CA242 showed sensitivity similar to that of CA19-9 for overall cases and early cases (stage I tumour) of pancreatic cancer. For other malignancies, the positive rates of CA242 were lower than those of CA19-9 except for colorectal cancer. An important characteristics of CA242 was that it was only slightly and infrequently elevated in the sera of patients with benign diseases such as chronic pancreatitis, chronic hepatitis and liver cirrhosis. This characteristic was more apparent in the patients with benign obstructive jaundice, indicating that the serum level of this marker was scarcely affected by cholestasis. Using cut-off levels corresponding to a 90% specificity, the clinical results obtained with CA242 in the diagnosis of pancreatic cancer were similar to those obtained with CA19-9, except that CA19-9 was falsely negative in some patients with early-stage pancreatic cancer. These findings suggest the usefulness of this marker for screening pancreatic cancer in patients on their first hospital visit. However, CA242 was found to be influenced by the Lewis blood group system. This unfavourable result is attributed to the C241 catcher antibody of this assay system, which has almost the same epitope specificity as the C50 and the NS19-9 monoclonal antibodies. In conclusion, CA242 is superior to CA19-9 in diagnosing pancreatic cancer by virtue of its higher specificity.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1994

Epitope analysis of SPan-1 and DUPAN-2 using synthesized glycoconjugates sialyllact-N-fucopentaose II and sialyllact-N-tetraose.

Epitope analysis of SPan-1 and DUPAN-2 was compared with that of CA19-9 using the synthesized glycoconjugate sialyllacto-N-fucopentaose II (SLF II, sialyl-Lewis(a)) and its precursor, sialyllact-N-tetraose (LSTa, sialyl-Lewis(c)), conjugated to human serum albumin. The CA19-9 and DUPAN-2 assay systems specifically recognized SLF II and LSTa, respectively. The SPan-1 assay system recognized both SLF II and LSTa, although the reactivity with the former was far stronger than that with the latter. These results were, in general, compatible with those obtained from assaying these markers in the sera of two pancreatic cancer patients with definite Lewis-negative phenotype and in the sera of 39 CA19-9-negative pancreatic cancer patients. In conclusion, DUPAN-2 is the precursor of CA19-9 and is accumulated in the sera of pancreatic cancer patients with Lewis-negative phenotype and SPan-1 has an advantage over CA19-9 in the diagnosis of patients with Lewis-negative phenotype, although both markers have almost the same sensitivity for this malignancy.

Antibodies, Monoclonal↗

PubMed1994

[Clinical study of cyclic intra-arterial chemotherapy using mitoxantrone for advanced hepatocellular carcinoma].

Cyclic intra-arterial infusion chemotherapy using Mitoxantrone via reservoir system was prescribed for 8 patients with advanced hepatocellular carcinoma. According to the clinical staging system, two patients were in Stage III and the other six patients in Stage IV-A. Vp-3 portal invasion was observed in six out of the eight patients. Mitoxantrone (5-8 mg/body) was administered intra-arterially via port-a-cath device every 4 weeks. For tumor response, there were two PR cases, four NC cases, and two PD cases. Thus, the response rate was 25%. The mean survival period was 6.5 months, and 1-year survival rate was 13%. In one of two PR cases, the survival time has been more than two years so far. Gastrointestinal toxicities such as nausea and vomiting were not severe. Critical myelosuppression requiring medication was not observed. Although a temporary increase of serum bilirubin was found in two cases, no severe damage to hepatic function was observed. From our preliminary data, this arterial infusion chemotherapy using Mitoxantrone via reservoir system can be safely performed on non-hospitalized patients with advanced hepatocellular carcinoma, and may be a useful treatment modality.

Aged↗

PubMed1993

Steroid metabolism in the cortex and the medulla of the early fetal bovine ovary.

Suspensions of cells obtained from the cortex and the medulla of the ovary of early bovine fetuses of 4-10 cm in crown-rump (C-R) length were used for studies of the metabolism of radiolabeled exogenous steroid precursors. Tritiated dehydroepiandrosterone, androstenedione, and testosterone were employed as precursors and their metabolic products were evaluated after separation by thin-layer chromatography. The extent of conversion of tritiated dehydroepiandrosterone to androstenedione was higher in cells from medulla than in those from the cortex. Androstenedione was metabolized mainly to estrone, and the percent of transformation was similar in the cortex and the medulla, but the rate of formation of 17 beta-estradiol was higher in the medulla than in the cortex. Furthermore, cells obtained from the cortex and the medulla aromatized testosterone to 17 beta-estradiol at a similar rate. In all cases, the percent of transformation was higher in ovaries from fetuses of 4.0 cm in C-R length than those from fetuses of 9.0-10.0 cm in C-R length. These data suggest that, in the bovine fetal ovary, the activity of 3 beta-hydroxysteroid dehydrogenase/isomerase and 17 beta-hydroxysteroid dehydrogenase predominates in the medulla, whereas aromatase activity is similar in the cortex and the medulla of the early fetal bovine ovary.

Androstenedione↗

PubMed1993

Expression and purification of the HIV-1 reverse transcriptase using the baculovirus expression vector system.

We have successfully expressed and purified the human immunodeficiency virus type-1 reverse transcriptase (RT) using the baculovirus expression vector system. This expression system provides a eukaryotic environment in which post-translational modifications of foreign gene products can occur. After infection with recombinant virus, Western blot analysis confirmed the presence of an immunoreactive polypeptide of approximately 66 kDa from insect Sf9 cell lysates. RT was then purified from crude extracts of baculovirus-infected Sf9 cells; SDS-PAGE analysis of fractions obtain from partial purification showed that in contrast to the Escherichia coli-expressed RT, the baculovirus-expressed RT corresponded to a doublet of peptides at approximately 66 kDa. Further purification of the protein resulted in a p66 protein, judged to be more than 90% pure by SDS-PAGE and Coomassie blue stain. Following purification, the baculovirus derived RT had specific activity for DNA polymerase similar to that of the E. coli-derived RT. Therefore, RT purified from Sf9 cells appears to be suitable for structure-function studies of this enzyme.

Animals↗