Biomedical subjects

M Tada

Publications and source records attributed to M Tada.

At least 145 records · Page 8Linked to original sources

PubMed1998

Helicobacter pylori infection induces gastric cancer in mongolian gerbils.

BACKGROUND & AIMS: Although epidemiological studies have indicated that Helicobacter pylori infection plays a crucial role in gastric carcinogenesis in humans, there is no direct proof that H. pylori is actually associated with gastric carcinogenesis. The purpose of this study was to elucidate the relationship between H. pylori infection and gastric carcinogenesis using an animal model of long-term H. pylori infection. METHODS: Mongolian gerbils were orally inoculated with H. pylori, and the sequential morphological changes in the stomach were examined for up to 62 weeks. RESULTS: H. pylori was constantly detected in all infected animals throughout the study. At the 26th week, severe active chronic gastritis, ulcers, and intestinal metaplasia could be observed in infected animals. By the end of the study, adenocarcinoma had developed in the pyloric region of 37% of the infected animals. All tumors consisted of well-differentiated intestinal-type epithelium, and their development seemed to be closely related to intestinal metaplasia. CONCLUSIONS: We have successfully demonstrated that long-term infection with H. pylori induces adenocarcinoma in Mongolian gerbils. The observations are thus highly suggestive of the involvement of H. pylori infection in gastric carcinogenesis in humans.

Adenocarcinoma↗

PubMed1998

Germ cell tumours of the central nervous system: treatment consideration based on 111 cases and their long-term clinical outcomes.

Germ cell tumours (GCTs) of the central nervous system (CNS) encompass various histological subtypes, and their optimal management has been the subject of debate. To indicate a better management strategy for each subtype, we analysed the records of 111 patients (median age 14 years), who underwent treatment since 1970. With a median follow-up duration of 86 months, the probability of surviving 5 years was: 96% for pure germinoma patients, 100% for mature teratoma, 67% for immature teratoma and 69% immature teratoma mixed with germinoma. The probability of cause-specific progression of germinomas producing human chorionic gonadotropin (HCG) was higher than that of non-producing germinomas (P < 0.01). GCTs that included a highly malignant component, such as embryonal carcinoma or yolk sac tumour, exhibited a poor prognosis with 38% chance of 5-year survival. Late adverse effects of therapy included stroke, secondary malignancy and cognitive, endocrinological, auditory and visual dysfunctions. Of 85 survivors with a median follow-up period of 99 months, 58 patients needed hormone replacement therapy, 26 patients showed poor performance status and, to date, only 1 patient has fathered children. Because the outcomes varied widely for each subtype, the traditional categories, that is, germinoma and non-germinomatous GCT as an extrapolation from the gonadal GCTs, are not suitable for appropriately selecting therapeutic regimen for CNS GCTs.

Activities of Daily Living↗

PubMed1998

Molecular regulation of phospholamban function and expression.

Intracellular levels of cAMP regulated by the beta-adrenergic actions of catecholamines play a key in the metabolic, electrical, and mechanical performance of the cardiac muscles. Among a number of biological actions of cAMP, the excitation-contraction coupling process in cardiac myocytes is markedly affected by cAMP through its stimulatory effect on cAMP-dependent protein kinase. Phospholamban, which is expressed in the sarcoplasmic reticulum of cardiac, slow-twitch skeletal, and smooth muscles, is one of the substrates for cAMP-dependent protein kinase. Phospholamban regulates the activity of Ca ATPase in the sarcoplasmic reticulum membranes in a manner dependent on the phosphorylation state of cAMP-dependent protein kinase, thereby changing the mechanical performance of the cardiac muscles. This Ca regulatory mechanism of phospholamban-Ca ATPase system is mediated by a direct protein-protein interaction between two proteins. This review focuses on recent advances in understanding the role of phospholamban molecule in the regulation of Ca transport by cardiac muscle sarcoplasmic reticulum.

Journal Article↗

PubMed1998

Cisplatin/vincristine chemotherapy for hypothalamic/visual pathway astrocytomas in young children.

Hypothalamic/visual pathway astrocytomas in children are usually quiescent, but certain cases contain aggressive neoplasms that cause progressive neurological and visual deterioration. Radiotherapy is not recommended in young children because of its adverse effects later in life. This report describes the efficacy of a chemotherapeutic regimen. Four young children with hypothalamic/visual pathway astrocytoma, with a mean of 18 months of age at diagnosis, were treated with chemotherapy. Three patients had diencephalic syndrome at the disease's onset. Three patients with pilocytic astrocytoma were histologically verified, and another infant was clinically diagnosed. A combination chemotherapy using cisplatin and vincristine was administered in a total of 8 cycles in 3 children and 4 in one child. One patient who demonstrated renal insufficiency after 4 cycles of this regimen was treated with additional 4 cycles using carboplatin instead of cisplatin. The acute and subacute hematologic and otologic toxicities were mild, and a transient renal insufficiency in a child during chemotherapy improved. After chemotherapy, tumor regression was documented in 3 patients, and the disease was observed to be stable in one patient with an evidence of intratumoral necrosis on MRI. Three patients showed neurological and endocrinological improvements. These results suggest that this regimen is feasible in young children and may be useful as a first-line treatment for hypothalamic/visual pathway astrocytomas, which in turn may allow potentially deleterious irradiation on the maturing brain to be deferred until the disease progresses.

Antineoplastic Agents↗

PubMed1998

Human astrocytoma cells are capable of producing macrophage inflammatory protein-1beta.

We investigated expression of macrophage inflammatory protein-1 (MIP-1) alpha and beta in human astrocytoma cell lines and surgical specimens of astrocytic tumors. Enzyme-linked immunosorbent assay (ELISA) showed constitutive secretion of MIP-1alpha protein in only one and MIP-1beta in none of 7 cell lines tested. However, MIP-1alpha production was increased in three cell lines by stimulation with lipopolysaccharide (LPS) and 5 cell lines by stimulation with phorbol-12myristate-13-acetate (PMA). Also, induction of MIP-1beta production was observed in one cell line with LPS stimulation and in two cell lines with PMA stimulation. Reverse-transcription polymerase chain reaction (RT-PCR) showed the increase of MIP-1alpha and beta mRNA expression in these cell lines. The increase of the mRNA with the stimuli was further confirmed by Northern blot analysis. In contrast, RT-PCR analysis revealed that the majority of the tested tumor specimens of high-grade.astrocytomas expressed both MIP-1alpha and MIP-1beta mRNAs. ELISA detected MIP-1beta protein in 1 of 11 cerebrospinal fluid samples from patients with high-grade astrocytoma and in 8 of 9 tumor cyst fluid samples, whereas MIP-1alpha was detected in only 1 cyst fluid somple. Taken together, these results indicate that astrocytic tumor cells are capable of expressing and producing MIPs, and suggest that MIPs may participate in the inflammatory responses commonly seen in astrocytic tumors.

Astrocytoma↗

PubMed1998

Quantitative analysis of ras gene mutation in pancreatic juice for diagnosis of pancreatic adenocarcinoma.

It has recently been demonstrated that mutant ras gene was also detected in patients with mucinous cell hyperplasia without adenocarcinoma, indicating that the presence of the mutation could not be a definite marker for pancreatic adenocarcinoma. The present study was performed to differentiate pancreatic adenocarcinoma from others by quantification of mutant ras gene in pancreatic juice. By measuring mutant ras gene by polymerase chain reaction (PCR) during its logarithmic phase, the amount was semiquantitatively evaluated between 0.1 and 10% of total DNA that was extracted from pancreatic juice obtained via endoscopy. Semiquantitative analysis revealed that the mutant gene occupied more than 1% of total DNA in eight of 15 patients (53%) with pancreatic adenocarcinoma, and in all three patients (100%) with intraductal papillary neoplasm of the pancreas, but in only two of 19 cases (11%) without neoplasm. Semiquantitative analysis may provide a clinical tool for the differential diagnosis of pancreatic carcinoma.

Adenocarcinoma↗

PubMed1998

Monitoring adenoviral p53 transduction efficiency by yeast functional assay.

Monitoring the transduction efficiency is of paramount importance in gene therapy. To monitor adenovirus-mediated wild-type p53 gene transfer, we have used a quantitative assay which tests the ability of human p53 to activate transcription in yeast. Selective amplification of cellular and viral p53 transcripts followed by quantitative assessment of mutant p53 content with the assay permits measurement of the wild-type p53 transduction efficiency into SF-188, U251MG and HUG31 glioblastoma cells. One reverse transcription primer tracks the wild-type/mutant ratio of endogenous p53 mRNA (P2), and the other the wild-type/mutant ratio of both endogenous and exogenous p53 mRNA (P1). Following infection of cell lines homozygous for mutant p53, the apparent transduction efficiency calculated (tau 0 = [P1-P2]/[1 + P2]) correlated with the level of p21 expression. Transduction efficiency in heterozygous wild-type/mutant HUG31 cells increased linearly with multiplicity of infection (MOI) for tau 0 values between 0.5 and 5.9, and admixture of normal cell-derived RNA produced only a modest reduction in tau 0 value, in keeping with theoretical predictions. These results suggest that the yeast p53 functional assay may be a useful tool for monitoring p53 gene therapy.

Adenoviridae↗

PubMed1998

Endoscopic papillary balloon dilation for the management of common bile duct stones: experience of 226 cases.

BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy is a widely accepted technique for the treatment of patients with common bile duct stones. However, it is still associated with occasional complications. The recently developed technique of endoscopic papillary balloon dilation seems to be a safe and effective procedure, and to have great potential for replacing endoscopic sphincterotomy. However, few reports have been published on the use of this technique for bile duct stones. The present study was undertaken to evaluate its safety and efficacy. PATIENTS AND METHODS: Endoscopic papillary balloon dilation was used to remove common bile duct stones in 226 consecutive patients including 41 patients of ASA classification III/IV, 41 elderly patients (> 80 years) 24 with liver cirrhosis, and 86 with periampullary diverticulum. After dilation of the papilla with a balloon diameter of 8 mm, the stones were retrieved. RESULTS: In conjunction with the use of a mechanical or/and electrohydraulic lithotriptor in 79 patients (35%) with large stones (> 10 mm in diameter), clearance of the common bile duct was achieved in 225 of 226 patients (99%) without serious complications, such as hemorrhage or severe pancreatitis; mild (n = 13) or moderate (n = 2) pancreatitis occurred in 7% of cases. CONCLUSIONS: Endoscopic papillary balloon dilation is a safe and effective technique for the treatment of common bile duct stones, even in high-risk patients.

Adult↗

PubMed1998

Isolation of a tobacco cDNA encoding Sar1 GTPase and analysis of its dominant mutations in vesicular traffic using a yeast complementation system.

The cDNA clone of NtSAR1, a gene encoding the small GTPase Sar1p which is essential for vesicle formation from the endoplasmic reticulum (ER) membrane in yeast, has been isolated from Nicotiana tabacum BY-2 cells. NtSAR1 as well as AtSAR1 cDNA isolated from Arabidopsis thaliana [d'Enfert et al. (1992) EMBO J. 11: 4205] could complement the lethality of the disruption of SAR1 in yeast cells in a temperature-sensitive fashion. They also suppressed yeast sec12 and sec16 temperature-sensitive mutations as yeast SAR1 does. Using this complementation system, we analyzed the phenotypes of several mutations in plant SAR1 cDNAs in yeast cells. The expression of NtSAR1 H74L and AtSAR1 N129I showed dominant negative effect in growth over the wild-type SAR1, which was accompanied by the arrest of ER-to-Golgi transport. Such dominant mutations will be useful to analyze the role of membrane trafficking in plant cells, if their expression can be regulated conditionally.

Amino Acid Sequence↗

PubMed1998

Significant correlation of nitric oxide synthase activity and p53 gene mutation in stage I lung adenocarcinoma.

Nitric oxide (NO) and its derivatives can directly cause DNA damage and mutation in vitro and may play a role in the multistage carcinogenic process. It has been reported that NO induces mutation in the p53 tumor suppressor gene; we therefore analyzed the relationship between NO synthase (NOS) activity and p53 gene status in early-stage lung adenocarcinoma. Surgical samples were classified into two categories: 14 lung adenocarcinomas with high NOS activity (>25 pmol/min/g tissue, category A), and 16 with low NOS activity (<25 pmol/min/g tissue, category B). A yeast functional assay for p53 mutations disclosed a red colony that corresponded to a mutation in the p53 gene in 8 cases (57.1%) in category A and 3 cases (18.8%) in category B, the frequency being significantly higher in the former (P<0.05). A p53 DNA sequence analysis revealed that 5 of the 8 p53 mutation-positive samples in category A had a G:C-to-T:A transversion, which is reported to be a major target of NO. The mechanism of carcinogenesis of adenocarcinoma is not fully understood, but these results suggest that an excess of endogenously formed NO may induce a p53 gene mutation containing mainly G:C-to-T:A transversion in the early stage of lung adenocarcinoma. Our results suggest that NO has potential mutagenic and carcinogenic activity, and may play important roles in human lung adenocarcinoma.

Adenocarcinoma↗

PubMed1998

Case report: hypoechoic submucosal nodules: a sign of Epstein-Barr virus-associated early gastric cancer.

The Epstein-Barr virus (EBV) has been reported to be detectable in about 10% of gastric carcinomas. We performed a comparative study of endosonographic findings of EBV-positive and -negative early gastric carcinomas. Epstein-Barr virus was detected in 11.8% (four of 34) of endosonographically observed early gastric carcinoma lesions. Endoscopic ultrasonography (EUS) revealed a hypoechoic mass in the third layer, which reflected submucosal nodules, in 75% (three of four) of EBV-associated lesions. Endoscopically, in 66.7% (two of three) of EBV-associated carcinomas, the depressed lesion was surrounded by a raised margin covered with normal mucosa and was similar to a submucosal tumour (P < 0.05). Histologically, all three cases of EBV-associated lesions with submucosal tumour invasion had submucosal nodules of carcinoma with lymphoid stroma and 75% (three of four) were located in the gastric body. The ratio of maximal thickness to width of EBV-associated lesions was significantly larger than that of EBV-negative lesions, and this tendency was marked in lesions with submucosal tumour invasion (P < 0.05). This study indicated that EUS and endoscopy are of great use for the determination of EBV association with early gastric carcinoma.

Adult↗

PubMed1998

Mucoadhesive microspheres containing amoxicillin for clearance of Helicobacter pylori.

In an effort to augment the anti-Helicobacter pylori effect of amoxicillin, mucoadhesive microspheres, which have the ability to reside in the gastrointestinal tract for an extended period, were prepared. The microspheres contained the antimicrobial agent and an adhesive polymer (carboxyvinyl polymer) powder dispersed in waxy hydrogenated castor oil. The percentage of amoxicillin remaining in the stomach both 2 and 4 h after oral administration of the mucoadhesive microspheres to Mongolian gerbils under fed conditions was about three times higher than that after administration in the form of a 0.5% methylcellulose suspension. The in vivo clearance of H. pylori following oral administration of the mucoadhesive microspheres and the 0.5% methylcellulose suspension to infected Mongolian gerbils was examined under fed conditions. The mucoadhesive microspheres and the 0.5% methylcellulose suspension both showed anti-H. pylori effects in this experimental model of infection, but the required dose of amoxicillin was effectively reduced by a factor of 10 when the mucoadhesive microspheres were used. In conclusion, the mucoadhesive microspheres more effectively cleared H. pylori from the gastrointestinal tract than the 0.5% methylcellulose suspension due to the prolonged gastrointestinal residence time resulting from mucoadhesion. A dosage form consisting of mucoadhesive microspheres containing an appropriate antimicrobial agent should be useful for the eradication of H. pylori.

Amoxicillin↗

PubMed1998

Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes.

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined: Interleukin-1 beta induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS, L-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso-N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2 (0.1 mM, 1 h). Inhibition of iNOS with N omega-nitro-L-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

1-Methyl-3-isobutylxanthine↗

PubMed1998

Bix1, a direct target of Xenopus T-box genes, causes formation of ventral mesoderm and endoderm.

Brachyury, a member of the T-box gene family, is required for posterior mesoderm and notochord differentiation in vertebrate development, and mis-expression of Xenopus Brachyury causes ectopic mesoderm formation. Brachyury is a transcription activator, and its ability to activate transcription is essential for its biological function, but Brachyury target genes have proved difficult to identify. Here we employ a hormone-inducible Brachyury construct and subtractive hybridization to search for such targets. Using this approach we have isolated Bix1, a homeobox gene expressed both in the marginal zone of Xenopus and in the vegetal hemisphere. Expression of Bix1 is induced in an immediate-early fashion by mesoderm-inducing factors such as activin as well as by the products of the T-box genes Xbra and VegT (also known as Antipodean, Brat and Xombi). Activation of Bix1 in response to Xbra is direct in the sense that it does not require protein synthesis, and both Xbra and VegT activate expression of a reporter gene driven by the Bix 5' regulatory region, which contains an Xbra/VegT binding site. Mis-expression of low levels of Bix1 causes formation of ventral mesoderm, while high levels induce endodermal differentiation. These results suggest that Bix1 acts downstream of both VegT and Xbra to induce formation of mesoderm and endoderm.

Activins↗

PubMed1998

Involvement of the sonic hedgehog, patched 1 and bmp2 genes in patterning of the zebrafish dermal fin rays.

The signaling molecule encoded by Sonic hedgehog (shh) participates in the patterning of several embryonic structures including limbs. During early fin development in zebrafish, a subset of cells in the posterior margin of pectoral fin buds express shh. We have shown that regulation of shh in pectoral fin buds is consistent with a role in mediating the activity of a structure analogous to the zone of polarizing activity (ZPA) (Akimenko and Ekker (1995) Dev. Biol. 170, 243-247). During growth of the bony rays of both paired and unpaired fins, and during fin regeneration, there does not seem to be a region equivalent to the ZPA and one would predict that shh would play a different role, if any, during these processes specific to fish fins. We have examined the expression of shh in the developing fins of 4-week old larvae and in regenerating fins of adults. A subset of cells in the basal layer of the epidermis in close proximity to the newly formed dermal bone structures of the fin rays, the lepidotrichia, express shh, and ptc1 which is thought to encode the receptor of the SHH signal. The expression domain of ptc1 is broader than that of shh and adjacent blastemal cells releasing the dermal bone matrix also express ptc1. Further observations indicate that the bmp2 gene, in addition to being expressed in the same cells of the basal layer of the epidermis as shh, is also expressed in a subset of the ptc1-expressing cells of the blastema. Amputations of caudal fins immediately after the first branching point of the lepidotrichia, and global administration of all-trans-retinoic acid, two procedures known to cause fusion of adjacent rays, result in a transient decrease in the expression of shh, ptc1 and bmp2. The effects of retinoic acid on shh expression occur within minutes after the onset of treatment suggesting direct regulation of shh by retinoic acid. These observations suggest a role for shh, ptc1 and bmp2 in patterning of the dermoskeleton of developing and regenerating teleost fins.

Animals↗

PubMed1998

Purification method for human plasma kallikrein by a new affinity chromatography.

We synthesized a new affinity gel (PKSI-Toyopearl) using a selective synthetic inhibitor of plasma kallikrein (PKSI-527) as an affinity ligand, and employed it for the rapid purification of plasma kallikrein from human plasma. Human plasma activated with kaolin after acid treatment was applied to a PKSI-Toyopearl column. Adsorbed protein was eluted with 50 mM glycine-hydrochloric acid buffer (pH 3.0). Plasma kallikrein was purified 181-fold with a yield of 85% from the kaolin-activated plasma. Further purification was performed by chromatography on a DEAE-Toyopearl 650M column. Plasma kallikrein was finally purified 1720-fold with a 63% yield by these procedures. On sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, a band was observed at approximately 88 kDa. These findings indicate that PKSI-Toyopearl is a valuable tool for the purification of plasma kallikrein from human plasma.

Blood↗

PubMed1998

Effects of gonadal hormones on the zonal expression of rat hepatic phenol sulfotransferases.

Estradiol benzoate (EB) and testosterone propionate (TP) were administered to male and female Wistar rats, and their effects on the zonal expression of hepatic phenol sulfotransferase (P-ST) activities were determined at pH 5.5 and 7.4. Cytosolic fractions from periportal (PP) and perivenous (PV) hepatocytes were prepared by the dual-digitonin-pulse perfusion technique. In control rats, P-ST activities assayed at pH 5.5 and 7.4 were higher in males than in females, and were higher in the PV fraction than in the PP fraction in both sexes. P-ST activities were increased by the administration of TP in the PP and PV fractions of females, whereas the same treatment diminished the enzyme activities in both fractions of the males. EB administration gave reduced P-ST activity at pH 5.5 of both fractions, irrespective of sex, but not a marked difference at pH 7.4. Chromatofocusing of PP and PV fractions revealed the presence of P-ST isoforms eluted at approx. pH 8.0 (peak 1), 7.5 (peak 2), 7.0 (peak 3) and 6.0 (peak 4). In male rats, peak 3, which showed high enzyme activity at pH 5.5 in the PP and PV fractions, was markedly decreased by EB treatment, whereas in females, peak 3 was present only in the PV fraction and was not affected by EB administration. TP treatment did not show remarkable changes in P-ST peaks in the males, while peaks 2 and 3 were increased in the females. Immunoblot analysis revealed the presence of multiple P-ST isoforms which showed different immunoreactivity and electrochemical properties.

Animals↗

PubMed1998

Design of plasma kallikrein inhibitors: functional and structural requirements of plasma kallikrein inhibitors.

The synthetic plasma kallikrein (PK) inhibitor trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyme thylanilide (PKSI-527) consists of three parts. Each part was replaced by analogues in an attempt to improve the potency and the selectivity of PKSI-527. Among the peptides examined, trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyan ilide (peptide 16) inhibited PK with a high selectivity and an IC50 value of 2.7 microM, being as potent as PKSI-527.

Drug Design↗