Biomedical subjects

K Adachi

Publications and source records attributed to K Adachi.

At least 199 records · Page 11Linked to original sources

PubMed1998

In vitro effects of endothelin-1 on somatostatin and thyrotropin-releasing hormone release from the rat stomach.

The effects of endothelin (ET) 1 on the release of somatostatin (SS) and thyrotropin-releasing hormone (TRH) from the rat stomach were studied in vitro. The rat stomach was incubated in medium 199 with 1.0 mg/ml of bacitracin (pH 7.4) for 20 min. The amounts of SS and TRH released into the medium were measured by individual radioimmunoassays. With the addition of ET-1, the release of SS from the rat stomach was inhibited significantly in a dose-related manner, whereas TRH released from the stomach was enhanced significantly. These effects of ET-1 on SS or TRH release were blocked by BQ-485, a blocker of ETA receptor. These findings suggest that ET-1 inhibits SS and stimulates TRH release from the rat stomach in vitro, and that these effects are mediate via ETA receptor.

Animals↗

PubMed1998

Evidence for a critical role of DNA topoisomerase IIalpha in drug sensitivity revealed by inducible antisense RNA in a human leukaemia cell line.

To examine the role of human DNA topoisomerase IIalpha (topo IIalpha) in drug resistance, we selectively inhibited topo IIalpha gene expression in U937 human monocytic leukaemia cells stably transfected with a plasmid that allowed for Zn-mediated conditional expression of a human alpha-topo IIalpha antisense sequence. Expression of topo IIalpha mRNA was reduced to <30%, whereas no significant alteration of topo IIbeta mRNA expression was observed. Under these conditions, drug sensitivity to the topo-II-directed agents, etoposide and daunorubicin, was reduced to approximately 50%, whereas sensitivity to 4-hydroperoxy-cyclophosphamide (4-HC) was not altered. This suggests that a reduced amount of topo IIalpha mRNA may be sufficient for the resistance to topo II inhibitors in leukaemia cells.

Antibiotics, Antineoplastic↗

PubMed1998

Activation of JNK pathway and induction of apoptosis by manganese in PC12 cells.

Manganese is known to induce neurological disorders similar to parkinsonisms. A dopamine deficiency has been demonstrated in Parkinson's disease and in chronic manganese poisoning, suggesting that the mechanisms underlying the neurotoxic effects of the metal ion are related to a functional abnormality of the extrapyramidal system. However, the details have yet to be elucidated. Here we report that manganese causes characteristic internucleosomal DNA fragmentation, a biochemical hallmark of apoptosis, in PC12 cells. It was transcription dependent, relatively specific for manganese, and blocked in Bcl-2-overexpressed PC12 cells. The results indicate that apoptosis may play a role in the dopaminergic neurotoxicity associated with manganese, the first metal to be reported to induce this form of cell death. The early biochemical events show the impairment of energy metabolism, and the process may require new synthesis of proteins such as c-Fos and c-Jun. In addition, manganese induces phosphorylation of c-Jun at Ser63 and Ser73 and SEK1/MKK4 (c-Jun N-terminal kinase kinase) at Thr258 and tyrosine phosphorylation of several proteins. These results indicate that manganese activates specific signal cascades including the c-Jun N-terminal kinase pathway.

Animals↗

PubMed1998

An assessment of local curability of endoscopic surgery in early gastric cancer without satisfaction of current therapeutic indications.

BACKGROUND AND STUDY AIMS: Therapeutic endoscopy for early gastric cancer has been established with strict criteria for indications. In the present study, we evaluated the efficacy of endoscopic treatment in cases that did not fulfil the standard therapeutic criteria, consisting of well differentiating mucosal adenocarcinomas less than 2 cm in size and without an ulcer or a scar. PATIENTS AND METHODS: Sixty nine early gastric cancers in 64 patients that did not fulfil the standard criteria were treated endoscopically, and a rate of cure was retrospectively assessed during a mean follow-up of 5.2 years. Endoscopic treatment consisted of mucosal resection or thermal methods, or both. RESULTS: Curative resection was achieved in 19/20 (95%) of cases which came into one of the following categories, all being well differentiated adenocarcinomas, less than 3.0 cm in size, without ulcer or the scar of an ulcer, with invasion limited to mucosal layer (depth m); tumors less than 2.0 cm, with an ulcer or scar, depth m; tumors less than 2.0 cm, without ulcer or scar, invading the submucosa but in which invasion was limited to the superficial portion (depth sm-1); and poorly differentiated tumors less than 1.0 cm in size, without an ulcer or scar, depth m. The rate of cure in this group was statistically similar to the cure rate of cases that fulfilled the standard criteria (98%). CONCLUSIONS: Our retrospective results suggest that the indications for curative treatment of early gastric cancer could be expanded. Prospective studies are required.

Adenocarcinoma↗

PubMed1998

Immunohistochemical analysis of a case of gastritis cystica profunda associated with carcinoma development.

We report a rare case of gastritis cystica profunda (GCP) accompanied by carcinoma that developed in a 51-year-old Japanese man without antecedent gastric surgery. The polypoid tumor was located in the upper body of the resected stomach. Histologically, it was characterized by herniation of surface epithelium and cystic glands in the submucosa, muscularis propria, and subserosa. Marked chronic atrophic gastritis was found throughout the stomach, and dysplastic epithelia and a few adenocarcinoma cells were found in the deeper parts of the GCP. The Ki-67, p53, and p21WAF1/CIP1 labeling indices for the deeper part of the GCP were higher than those for the superficial parts or the surrounding mucosa, suggesting that both epithelial cell proliferation and p53-dependent p21WAF1/CIP1 expression in DNA-damaged cells, which might be associated with gastritis, are enhanced in line with penetration of glands. The underlying mechanisms might be linked in a chain of factors leading to malignancy.

Adenocarcinoma↗

PubMed1998

A combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than is ursodeoxycholic acid monotherapy.

Inhibitors of 3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase have been reported to decrease the cholesterol saturation index (CSI) in duodenal bile in humans and to prevent formation of cholesterol gallstones in animal studies. We performed a prospective study to evaluate the role of HMG-CoA reductase inhibitors as gallstone-dissolving agents. Fifty patients with radiolucent gallstones in a gallbladder opacifying at drip infusion cholecystography were treated with either 10 mg/day simvastatin plus 600 mg/day ursodeoxycholic acid (group 1, n=26) or 600 mg/day ursodeoxycholic acid alone (group 2, n=24) for 12 months. The ratio of solitary to multiple gallstone cases was 21:29. Plasma lipid levels were assessed and ultrasonographic examination of the gallbladder was performed at baseline and at 3-month intervals during treatment. Duodenal bile sampling was performed in five patients in each group at baseline and after 12 months of treatment. Plasma cholesterol decreased significantly in group 1 but not in group 2. In solitary gallstone cases, no significant difference in dissolution rates was observed between groups 1 (3 of 9, 33%) and 2 (4 of 12, 33%). In contrast, the dissolution rate in multiple gallstone cases was significantly higher in group 1 (12 of 17, 71%) than in group 2 (3 of 12, 25%) (p < 0.01). Bile cholesterol saturation index was significantly decreased (p < 0.01) but did not significantly differ between the two groups. These results suggest that combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than ursodeoxycholic acid monotherapy in patients with multiple gallstones.

Bile↗

PubMed1998

Conservation of resources: indications for intensive care monitoring after upper airway surgery on patients with obstructive sleep apnea.

Although significant complications can result after upper airway surgery for obstructive sleep apnea (OSA), there is a lack of consensus regarding the most appropriate level of monitoring in the perioperative period. A retrospective analysis was performed on the operative records of 109 adult patients who underwent 125 surgical procedures from January 1, 1991, to May 31, 1996, with particular emphasis on complications that would have mandated intensive care monitoring and management. Airway complications occurred in one patient (0.8%), who became obstructed immediately after surgery; he responded to naloxone and suctioning. Five other patients (4%) suffered oxygen desaturation to levels below 90% (none fell below 80%, and in only one case was it below the lowest preoperative oxygen saturation level). Cardiac complications, primarily significant hypertension, were the most common adverse events. Four (3.2%) bleeding complications were encountered; all occurred after discharge from the hospital. Routine postoperative intensive care monitoring for all adult patients undergoing upper airway surgery for OSA is unnecessary. Although high-risk patients cannot always be identified preoperatively, significant complications generally emerge within 2 hours after surgery. Therefore a decision regarding the level of postoperative monitoring needed may be made with confidence during the period of time that the patient is in the recovery room.

Adult↗

PubMed1998

Divergent cAMP signaling pathways regulate growth and pathogenesis in the rice blast fungus Magnaporthe grisea.

cAMP is involved in signaling appressorium formation in the rice blast fungus Magnaporthe grisea. However, null mutations in a protein kinase A (PKA) catalytic subunit gene, CPKA, do not block appressorium formation, and mutations in the adenylate cyclase gene have pleiotropic effects on growth, conidiation, sexual development, and appressorium formation. Thus, cAMP signaling plays roles in both growth and morphogenesis as well as in appressorium formation. To clarify cAMP signaling in M. grisea, we have identified strains in which a null mutation in the adenylate cyclase gene (MAC1) has an unstable phenotype such that the bypass suppressors of the Mac1(-) phenotype (sum) could be identified. sum mutations completely restore growth and sexual and asexual morphogenesis and lead to an ability to form appressoria under conditions inhibitory to the wild type. PKA assays and molecular cloning showed that one suppressor mutation (sum1-99) alters a conserved amino acid in cAMP binding domain A of the regulatory subunit gene of PKA (SUM1), whereas other suppressor mutations act independently of PKA activity. PKA assays demonstrated that the catalytic subunit gene, CPKA, encodes the only detectable PKA activity in M. grisea. Because CPKA is dispensable for growth, morphogenesis, and appressorium formation, divergent catalytic subunit genes must play roles in these processes. These results suggest a model in which both saprophytic and pathogenic growth of M. grisea is regulated by adenylate cyclase but different effectors of cAMP mediate downstream effects specific for either cell morphogenesis or pathogenesis.

Alleles↗

PubMed1998

Functional diversity of infiltrating macrophages in inflamed human colonic mucosa ulcerative colitis.

1. Phenotypical heterogeneity of macrophages infiltrating the colonic mucosa of patients with ulcerative colitis has been shown in many reports. The functional diversity of macrophages in inflamed colonic mucosa remains unclear. 2. Intestinal macrophages have been characterized by immunohistochemical staining and their ability to generate free oxygen radicals in inflamed and non-inflamed mucosa. 3. No correlation was found between RFD1 (activated dendritic cells), RFD7 (tissue macrophages) or RFD9 (epithelioid cells, giant cells in association with granuloma) positivity and either CD68 or human histocompatibility complex class II antigen (HLA-DR) positivity. The proportions of RFD7- and RFD9-positive cells were significantly increased in inflamed colonic mucosa. Nitroblue tetrazolium-reducing mononuclear cells were CD68 or RFD7 positive but they were rarely positive for HLA-DR and RFD1. 4. These results suggest that nitroblue tetrazolium-reducing macrophages are (scavenger) macrophages.

Cell Movement↗

PubMed1998

Intracellular changes in ions and organic solutes in halotolerant brevibacterium sp. Strain JCM 6894 after exposure to hyperosmotic shock

In the present study we aimed to observe the intracellular responses when there was a hyperosmotic shock with a large shift in ionic strength in nutrient-rich and nutrient-poor external environments in order to clarify the availability of substrates. To do this, we used the halotolerant organism Brevibacterium sp. strain JCM 6894, which is able to grow in the presence of a wide range of salt concentrations. Hyperosmotic shock was induced by transferring cells in the late exponential phase of growth in a complex medium containing 0.5 M NaCl into either old or fresh culture medium containing 2 M NaCl. Changes in the growth rate, in the pH of the medium, and in the internal cation or organic solute concentrations in the cytosol after an upshock were analyzed as a function of incubation time. The cells exhibited very different responses to upshocks in fresh culture medium and in old culture medium; in fresh culture medium, growth was stimulated and the medium became more acidic, whereas the old culture medium repressed growth and the medium became more alkaline. The intracellular free Na+ concentrations remained low (80 nmol mg of protein-1) after an upshock in fresh culture medium, although they quickly increased twofold in the old culture medium. In contrast, K+ ions immediately accumulated in the cells in fresh culture medium, whereas K+ ions were taken up quite slowly in old culture medium. Furthermore, the cells placed in fresh culture medium transiently accumulated alanine and glutamine in response to the upshock, but the cells placed in old culture medium did not. Growth of the Brevibacterium strain at higher levels of salinity was supported by ectoine synthesis but was not observed after the shift to high-osmolarity conditions in the old culture. In the fresh culture, however, ectoine was vigorously synthesized in cells for more than 5 h after the upshock; the concentration of ectoine in cells was more than 3,500 nmol mg of protein-1 at 10 h, which corresponded to a ninefold increase compared to the concentration before the shock. These findings are consistent with the results of an analysis of the extracellular medium composition before and after the upshock.

Journal Article↗

PubMed1998

A novel ATP-binding cassette transporter involved in multidrug resistance in the phytopathogenic fungus Penicillium digitatum.

Demethylation inhibitor (DMI)-resistant strains of the plant pathogenic fungus Penicillium digitatum were shown to be simultaneously resistant to cycloheximide, 4-nitroquinoline-N-oxide (4NQO), and acriflavine. A PMR1 (Penicillium multidrug resistance) gene encoding an ATP-binding cassette (ABC) transporter (P-glycoprotein) was cloned from a genomic DNA library of a DMI-resistant strain (LC2) of Penicillium digitatum by heterologous hybridization with a DNA fragment containing an ABC-encoding region from Botrytis cinerea. Sequence analysis revealed significant amino acid homology to the primary structures of PMR1 (protein encoded by the PMR1 gene) and ABC transporters of Saccharomyces cerevisiae (PDR5 and SNQ2), Schizosaccharomyces pombe (HBA2), Candida albicans (CDR1), and Aspergillus nidulans (AtrA and AtrB). Disruption of the PMR1 gene of P. digitatum DMI-resistant strain LC2 demonstrated that PMR1 was an important determinant of resistance to DMIs. The effective concentrations inhibiting radial growth by 50% (EC50s) and the MICs of fenarimol and bitertanol for the PMR1 disruptants (Deltapmr1 mutants) were equivalent to those for DMI-sensitive strains. Northern blot analysis indicated that severalfold more PMR1 transcript accumulated in the DMI-resistant strains compared with those in DMI-sensitive strains in the absence of fungicide. In both DMI-resistant and -sensitive strains, transcription of PMR1 was strongly enhanced within 10 min after treatment with the DMI fungicide triflumizole. These results suggested that the toxicant efflux system comprised of PMR1 participates directly in the DMI resistance of the fungus.

4-Nitroquinoline-1-oxide↗

PubMed1998

The isolation and characterization of androgen-dependent genes in the flank organs of golden Syrian hamsters.

To elucidate the molecular action of androgens, we have isolated two androgen-dependent genes, FAR-17a and -17c, from the cDNA library of flank organs of male golden Syrian hamsters by a differential hybridization method. FAR-17a has been reported previously. Androgens regulated the expression in the flank organs, ear lobe and skin. FAR-17a protein was located in sebaceous glands. FAR-17c has a similar expression pattern to that of FAR-17a, but its response to androgen is faster than that of FAR-17a. It is expressed strongly in the liver, sebaceous glands and brain. The homology search and mRNA expression pattern suggested that it might encode a stearyl CoA desaturase (SCD) of golden Syrian hamsters. The SCD is a key enzyme in fatty acid biosynthesis and its expression is controlled by temperature, nutritional conditions and hormones. This is the first report that the mRNA expression of stearyl CoA is regulated by androgens.

Amino Acid Sequence↗

PubMed1998

Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group.

PURPOSE: We conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL) and analyzed the prognostic factors for predicting complete remission (CR), event-free survival (EFS), and disease-free survival (DFS). PATIENTS AND METHODS: All patients received ATRA until CR. If patients had an initial leukocyte count greater than 3.0 x 10(9)/L, they received daunorubicin (DNR) and behenoyl cytarabine (BHAC). During therapy, if patients showed blast and promyelocyte counts greater than 1.0 x 10(9)/L, they received additional DNR and BHAC. After achieving CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. RESULTS: Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved CR. Multivariate analysis showed that no or minor purpura at diagnosis (P = .0046) and age less than 30 years (P = .0076) were favorable factors for achievement of CR. Predicted 4-year overall survival and EFS rates were 74% and 54%, respectively, and the 4-year predicted DFS rate for 173 CR patients was 62%. Multivariate analysis showed that age less than 30 years (P = .0003) and initial leukocyte count less than 10 x 10(9)/L (P = .0296) were prognostic factors for longer EFS, and initial leukocyte count less than 10.0 x 10(9)/L was a sole significant prognostic factor for longer DFS (P = .0001). CONCLUSION: Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for APL treated with ATRA followed by intensive chemotherapy.

Adolescent↗

PubMed1998

The relation between the pacing sites in the right ventricular outflow tract and QRS morphology in the 12-lead ECG.

Optimal pace mapping is a good predictor of the appropriate ablation site for idiopathic right ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT). We studied the relationship between the RVOT pacing site and QRS morphology in the 12-lead ECG during pacing to find the optimal site more quickly. In 13 patients with idiopathic VT, pacing at 8 sites in the RVOT (free wall, septum, and anterior and posterior regions of upper and lower sites) was performed while 12-lead ECGs were recorded. The R-wave amplitude minus the S-wave amplitude in lead I (RI-SI) and aVF (RavF-SavF) and the transitional zone index (TZI) were compared in the different pacing sites; TZI was defined to examine the transitional zone as a value. The RI-SI was smaller in the anterior region than in the other regions, and the negative RI-SI predicted that the pacing site was in the upper or lower anterior regions. The RavF-SavF was larger in the septum and anterior regions than in the free wall and posterior regions. The TZI was larger in the free wall region than in the septum. From the results, we constructed a flow chart that differentiates the origin of the arrhythmia in the RVOT and a directional guide that indicates the direction from the current mapping site for optimal pace mapping. The results provided an ECG guide for locating the focus of VT originating from the RVOT. These findings may systematically improve the mapping procedure.

Adolescent↗

PubMed1998

[Techniques for evaluating neuronal death of the retina in vitro and in vivo].

This review describes the techniques to evaluate retinal neurodegeneration induced by excitatory amino acids and transient ischemia. Glutamate-induced neurotoxicity was examined in cultured rat cortical cells. Cultures obtained from the retinas of fetal rats were incubated in Eagle's minimal essential medium supplemented with 10% fetal calf serum or 10% horse serum at 37 degrees C in a humidified 5% CO2 atmosphere for 10-14 days. The neurotoxicity induced by glutamate was quantified by trypan blue exclusion. The viability of cultures was markedly reduced by a 10-min exposure to glutamate followed by incubation with glutamate-free medium for 1 hr. N-methyl-D-aspartate (NMDA)-induced retinal damage was examined in adult rats. Transverse sections of the retinas through the optic disk were stained with hematoxylin and eosin. A single intravitreal injection of NMDA damaged the ganglion cell layer and the inner plexiform layer without affecting the other retinal layers 7 days after injection. Retinal ischemia was induced by elevating the intraocular pressure for 45 min through the needle which was placed in the anterior chamber. Ischemia-induced retinal damage was inhibited by MK-801. These results indicate that the techniques described in this review can be employed to develop new drugs possessing neuroprotective action against neurodegeneration that occurs during retinal ischemia.

Animals↗

PubMed1998

Purification and properties of a novel sulfatase from Pseudomonas testosteroni that hydrolyzed 3 beta-hydroxy-5-cholenoic acid 3-sulfate.

A novel sulfatase hydrolyzing the sulfate ester bond in 3 beta-hydroxy-5-cholenoic acid 3-sulfate (delta 5-3 beta-sulfate) was purified from Pseudomonas testosteroni ATCC 11996 as the second bile acid sulfatase. The molecular weight was 95,000 and the molecule was composed of a homodimer of a subunit of which the molecular weight was 46,000. This sulfatase hydrolyzed delta 5-3 beta-sulfate to 3 alpha-hydroxy-5-cholenoic acid and sulfuric acid with inversion of beta- to alpha-configuration of the hydroxyl group at the C-3 position of the substrate. The optimum pH and the stable pH of the enzyme were 8.5 and 6.5-9.7, respectively. 3 beta-Sulfate ester bonds of steroids such as isolithocholic acid, pregnenolone, and epiandrosterone, in which the side chain of the steroid ring was shorter than cholesterol, were also hydrolyzed to 3 alpha-hydroxyl compounds corresponding to each steroid compound and sulfuric acid. We tentatively named this novel enzyme bile acid 3 beta-sulfate sulfohydrolase (beta-BSS).

Arylsulfatases↗

PubMed1998

Significant decrease of serum vitamin A level in Japanese Black beef steers after introduction to a farm.

Significant decrease of serum vitamin A (V.A) level in 4 out of 5 Japanese Black beef steers on day 7 after introduction was described in the present study. The feeder steers were fed the diets containing much more V.A than they required. In the farm where they were introduced, the productivity was high and the frequency was low in bovine cases of death and disease. The herd management; i.e. feeding method and environment of the farm were properly arranged. Results obtained from blood serum analyses revealed that health and nutritional status of the feeder steers were good on the day of introduction. The feeder steers, clinically healthy on the day of introduction, manifested mild bronchitis and diarrhea on days 2 and 10 after introduction, respectively, and slightly decreased dietary intake on both days. Serum V.A levels of the feeder steers were within the normal range. However, significantly decreased serum V.A level was detected in 4 feeder steers out of 5 on day 7 after introduction. This may be attributed to stress-increased V.A consumption rather than the decreased V.A intake.

Animal Feed↗

PubMed1998

Quantitative kinetic analysis of blood vessels in the outer membranes of chronic subdural hematomas.

Dynamic biologic modeling was used to calculate the transfer rate constant for gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) and capillary permeability in the outer membrane of chronic subdural hematomas and effusions. Following intravenous Gd-DTPA injection, Gd concentrations in the subdural fluid and in timed arterial blood samples were measured by ion-coupled plasma emission spectrometry in 53 chronic subdural hematomas and 18 chronic subdural effusions. The capillary surface area in outer membrane was assessed morphometrically. Transfer rate constants for subdural hematomas and subdural effusions were 12.4 +/- 1.0 and 20.6 +/- 1.7 (x 10(-4)min-1, respectively. Capillary permeabilities for subdural hematomas and subdural effusions were 16 +/- 1.2 and 19 +/- 3.7 ml.min-1(mm2/mm3)-1, respectively. The capillary surface areas for subdural hematomas and subdural effusions were 48 +/- 3 and 77 +/- 10 mm2/mm3, respectively. The high degree of infiltration of Gd into subdural effusions reflects the high capillary surface area in the outer membrane rather than greater permeability of individual capillaries. The value of transfer rate constant was correlated inversely with the duration of the chronic subdural fluid collection. Immature outer membrane has a high transfer rate constant which allows extravasation of plasma components into the subdural space, resulting in increasing volume of the subdural effusion. Delayed magnetic resonance imaging following Gd administration may be clinically useful for estimating the age of chronic subdural fluid accumulations.

Aged↗