Search PubMed⌕ Search

Biomedical subjects

H Kaneko

Publications and source records attributed to H Kaneko.

At least 19 recordsLinked to original sources
PubMed1995

Selective inhibition of gastrulation in the starfish embryo by albuside B, an inosine analogue.

External application of 0.2-100 micrograms/ml albuside B inhibits gastrulation of the starfish (Asterina pectinifera) embryo. Treated embryos retain the late blastula morphology with the vegetal plate. However, the vegetal plate is unreactive to soybean agglutinin, a probe for observing the progenitor cells of the archenteron (mesendoderm) in a normal embryo. The effective period of the treatment is limited from 4 to 6 h after fertilization, a period immediately before the onset of blastulation. RNA synthesis is unaffected during the period of sensitivity. The selectivity of the inhibition shows that albuside B may be a useful tool for studying the mechanisms of mesendoderm differentiation.

Animals↗
PubMed1995

Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p230 BCR/ABL fusion protein.

The cell line AR230 was established from the peripheral blood mononuclear cells of a patient with chronic myeloid leukemia and t(9;22) translocation bearing a variant type of BCR/ABL rearrangement. AR230 expresses a BCR/ABL fusion protein with a molecular mass of 230 kilodaltons (kDa) due to the insertion of 180 amino acids encoded by 3' exons of BCR (b4 to c3). An immune complex kinase assay showed that the 230-kDa BCR/ABL protein ahd autophosphorylation activity. Immunoprecipitation analysis revealed a stable complex of GRB2 and 230-kDa BCR/ABL proteins, indicating that the Ras activation pathway is involved in the process of transformation. AR230 expressed another short transcript consisting of a BCRc2/ABL junction, which is associated with a stop signal shortly after the junction. To our knowledge, this is the first cell line expressing a 230-kDa fusion product of BCR/ABL. AR230 will be useful for studying the biological function of divergent BCR/ABL proteins.

Amino Acid Sequence↗
PubMed1995

TP53 mutations emerge at early phase of myelodysplastic syndrome and are associated with complex chromosomal abnormalities.

We examined TP53 mutation in 57 patients with myelodysplastic syndrome (MDS) at either the MDS phase or at the terminal leukemic phase using polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis. TP53 mutations within exons 5 through 8 were found in seven patients. All these mutations were detected at the presentation of MDS whether these patients showed leukemic transformation or not. TP53 mutations were frequently found in patients with loss of the short arm of chromosome 17 (17p-) (three of seven patients with 17p-, 43%) and complex karyotypic abnormalities (five of 14, 38%). Among the seven patients with the TP53 mutation, four patients progressed to acute leukemia within 7 months from the diagnosis of MDS, and the remaining three died within 7 months without leukemic transformation. These findings suggest that mutations of the TP53 can be implicated in leukemic transformation and a poor prognosis in MDS.

Acute Disease↗
PubMed1995

Molecular cloning and characterization of mouse HS1.

Here we report the cloning of a cDNA and a genomic DNA encoding the mouse homolog of human HS1, a hematopoietic cell-specific protein-substrate of non-receptor type protein-tyrosine kinase(s). Sequence analysis of the mouse HS1 cDNA revealed that it is highly homologous to human HS1 (total percent match = 84%) especially in the amino-terminal half, which contains unique repeating motifs, and in the carboxyl-terminal Src-homology 3 domain. As is the human counterpart, the mouse HS1 gene is expressed exclusively in hematopoietic cells. Genomic fragments covering most of the HS1 gene were isolated and used to map this gene to mouse chromosome 16.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Effect of plaunotol on hypergastrinemia induced by long-term omeprazole administration in humans.

Omeprazole markedly inhibits basal and stimulated gastric acid secretion and has the ability to produce hypergastrinemia and hyperplasia of enterochromaffin-like cells in humans. On the other hand, plaunotol, an acyclic diterpene alcohol, has been reported to inhibit gastrin release by stimulating endogenous secretion release. We investigated the effect of plaunotol on serum gastrin levels after six to eight weeks of omeprazole (20 mg/day) administration in 22 patients (16 males, 6 females; mean age 52.3, range 36-70 years) with peptic ulcer disease. The patients were randomized to the following two groups: 11 subjects with omerprazole alone (single group) and 11 with omeprazole plus plaunotol (240 mg/day) (combination group) treatment. There were no significant differences between the two groups concerning age, sex, ulcer stage, ulcer history, environmental factors, and Helicobacter pylori (HP) prevalence. After complete drug(s) administration, serum immunoreactive (ir) -gastrin levels increased significantly in the single group (P < 0.001) in contrast to the combination group, and plaunotol significantly inhibited hypergastrinemia induced by omeprazole administration (P < 0.001). Significant increases in serum ir-calcitonin gene-related peptide concentrations were observed in the combination group compared to the single group (P < 0.05). However, there were no significant changes in sereum ir-secretin, somatostatin, and vasoactive intestinal polypeptide levels as well as ulcer healing and HP prevalence between the two groups. These findings suggest that plaunotol may suppress hypergastrinemia induced by long-term omeprazole administration, at least partly, via a certain brain-gut hormone affecting gastrin release.

Adult↗
PubMed1995

Nizatidine accelerates gastric emptying of a solid meal in rats.

Nizatidine, a new histamine-2-receptor antagonist, stimulates gastrointestinal motility in dogs and gastric emptying of liquids in rats. Effect of nizatidine on gastric emptying of a solid meal was investigated using a novel gastric emptying model in rats. Male Wistar rats (weighing 200-300 g) were supplied with powdered food containing 30 w/w% barium 14 hr before the beginning of the experiment and x-ray photography of rat stomach was taken under light ether anesthesia. Gastric emptying was assessed by percentage of a decrease in area 30 min after drug was injected intraperitoneally. There was a positive correlation between the area of the gastric outline and the weight of the gastric contents (r = 0.94, P < 0.01). Ether anesthesia itself did not affect gastric emptying. Nizatidine increased gastric emptying dose-dependently (emptied percentage; vehicle: 4.9 +/- 1.5%, 1 mg/kg: 7.2 +/- 0.4%, 3 mg/kg: 10.4 +/- 2.0%, 10 mg/kg: 16.7 +/- 4.9%, 30 mg/kg: 25.7 +/- 7.4%). N-Desmethyl nizatidine (NDM) also stimulated gastric emptying, but nizatidine S-oxide, cimetidine, an famotidine had no significant effects on gastric emptying. Nizatidine and neostigmine, but not NDM, at a subthreshold dose accelerated gastric emptying treated with a low dose of acetylcholine (0.1 mg/kg). Atropine (2 mg/kg, -30 min) did not modulate the gastroprokinetic action of nizatidine, but blocked that of NDM. These findings suggest that this noninvasive method may allow measurement of gastric emptying of solids accurately and that nizatidine and NDM facilitate gastric emptying probably mediated by a direct and/or an indirect (acetylcholinesterase inhibition) cholinergic mechanism.

Acetylcholine↗
PubMed1995

Effect of cold-restraint stress on immunoreactive thyrotropin-releasing hormone and immunoreactive somatostatin in the rat stomach.

The effects of cold-restraint stress on immunoreactive thyrotropin-releasing hormone (ir-TRH) and immunoreactive somatostatin (ir-SOM) concentrations in the rat stomach were investigated. Rats immobilized with a spring-loaded metallic plate were placed in a room maintained at 4 degrees C for 1-3 h and then decapitated serially for investigation. Gastric ir-TRH and ir-SOM concentrations were measured by individual radioimmunoassays. Cold-restraint stress induced gastric mucosal lesions as well as a decrease of the ir-TRH concentration in the glandular stomach, an increase of the ir-TRH concentration in the gastric juice, and a decrease in gastric pH. In contrast, this stress caused an increase of ir-SOM in the glandular stomach and a decrease of ir-SOM in the gastric juice. However, cold or restraint stress alone did not induce gastric mucosal lesions or changes in gastric ir-TRH and ir-SOM concentrations or the gastric pH. To clarify the endocrine influence of peripheral TRH, pretreatment with thyroid hormone was performed to inhibit elevation of the serum TRH level during cold-restraint stress. Despite this pretreatment, cold-restraint stress still induced ulcer formation, along with changes in gastric ir-TRH and ir-SOM concentrations and gastric pH. These findings suggest that changes in gastric ir-TRH and ir-SOM concentrations may be closely related to ulcer formation due to cold-restraint, and that TRH may act in a paracrine manner in the stomach.

Animals↗
PubMed1995

Assessment of adrenal surgery on creatinine clearance in patients with phaeochromocytoma.

Sequential changes in creatinine clearance (Ccr) were determined in 14 patients undergoing operation for phaeochromocytoma. All patients had been given alpha-adrenergic antagonists 2 weeks before surgery. In the younger group (mean age 40 +/- 2 years), Ccr improved following adrenal surgery. Urinary concentrations of epinephrine, norepinephrine and total catecholamines correlated inversely with Ccr. A similar inverse relationship was noted between tissue norepinephrine concentration expressed as microgram/g and Ccr to a lesser extent. In older patients (mean age 69 +/- 2 years) Ccr remained unchanged by this surgical procedure. No significant correlations were found between both parameters in the older group. It appears reasonable to presume that excessive amount of catecholamine plays an important role in the impairment of Ccr in relatively young patients with phaeochromocytoma, but other possibilities as regards the sequence of this phenomenon must be pursued in older patients.

Adrenal Gland Neoplasms↗
PubMed1995

Medullary thyrotropin-releasing hormone mediates vagal-dependent adaptive gastric protection induced by mild acid in rats.

BACKGROUND & AIMS: Adaptive gastric protection is dependent on vagal pathways in rats. It is hypothesized that medullary thyrotropin-releasing hormone (TRH), known to regulate vagal function, is part of the brain mechanisms mediating adaptive gastric protection. METHODS: Urethane-anesthetized rats were pretreated with either acute bilateral subdiaphragmatic vagotomy, sham operation, or intracisternal injection of purified control, TRH, or peptide YY antibody. Gastric lesions were assessed 75 minutes after orogastric administration of 1 mL of either vehicle or 0.35N HCl followed 15 minutes later by 0.6N or 1.0N HCl. RESULTS: Injection of 0.6N and 1.0N HCl induced gastric lesions covering 23.1% +/- 2.7% and 37.8% +/- 3.3% of the corpus mucosa, respectively. Pretreatment with 0.35N HCl resulted in 67.3% and 50.5% reductions in gastric lesions induced by 0.6N and 1.0N HCl, respectively. Subdiaphragmatic vagotomy or intracisternal injection of TRH antibody increased gastric lesions induced by 0.6N HCl to 32.2% +/- 2.2% and 42.9% +/- 5.6%, respectively, and completely abolished the protective effect of 0.35N HCl pretreatment. Control or peptide YY antibody injected intracisternally did not alter the gastric protection induced by mild acid. CONCLUSIONS: These results indicate that medullary TRH plays a role in the vagally mediated adaptive gastric protection induced by mild acid.

Adaptation, Physiological↗
PubMed1995

Caudal raphe-dorsal vagal complex peptidergic projections: role in gastric vagal control.

Subpopulations of raphe pallidus (Rpa) and raphe obscurus (Rob) neurons containing TRH, serotonin (5-HT), and substance P contribute projections to the dorsal vagal complex (DVC). Activation of Rpa and Rob neurons induces a vagal cholinergic-dependent stimulation of gastric secretory and motor function and modulates resistance of the gastric mucosa to gastric injury in rats and cats. The caudal raphe nuclei-DVC pathways containing TRH/5-HT are involved in mediating cold-induced vagal stimulation of gastric function and erosion formation. These results suggest that Rpa/Rob-DVC projections containing TRH/5-HT may be an important pathways in the medullary regulation of vagal activity to the viscera.

Afferent Pathways↗
PubMed1995

Neurofibromatosis 1 gene (NF1) mutation is a rare genetic event in myelodysplastic syndrome regardless of the disease progression.

Neurofibromatosis 1 gene (NF1) is a tumor suppressor gene and the product of which down-regulates Nras protein by its GTPase activating protein-related domain (NF1-GRD). Although the incidence of NF1 mutation was reported to be rare in the chronic phase of myelodysplastic syndrome (MDS), there have been no previous reports on its configuration in patients showing the disease progression. We examined NF1 in 50 patients with MDS including 9 who had progressed to more advanced stages and 16 to acute leukemia. Six patients had an Nras mutation. We carried out allele specific restriction analysis (ASRA) to detect a mutation at the first nucleotide A of codon 1423 (AAG), a mutational hot spot. We also employed a polymerase chain reaction mediated single strand conformation polymorphism (PCR-SSCP) method to confirm the result of ASRA and to detect a point mutation in other sequences of FLR exon. In consequence, ASRA disclosed wild type configuration and PCR-SSCP showed no aberrant band in any sample examined whether the samples harboured an Nras mutation or not. We conclude that NF1 mutation does not play a crucial role in the development and the progression of MDS.

Base Sequence↗
PubMed1995

Failure of IgG production due to a defect in the opening of the chromatin structure of I gamma 1 region in a patient with IgG and IgA deficiency.

Patients with common variable immunodeficiency (CVID) display reduced levels of two or all three of the major immunoglobulin isotypes, and the deficiency is characterized by failure of B cells to differentiate into plasma cells in many cases. A patient (14 years old, female) showed normal serum IgM levels and low serum IgG and IgA levels, including low levels of all IgG subclasses. Northern blot analysis suggested that the patient's B cells may be defective at the immunoglobulin heavy chain isotype switch. The germ-line C gamma 1 transcript was amplified from cDNA of healthy controls by the addition of recombinant IL-2 (rIL-2) to pokeweed mitogen-stimulated peripheral mononuclear cells or Staphylococcus aureus Cowan I (SAC)-stimulated IgM-producing lymphoblastoid cell lines (LCL) transformed by Epstein-Barr virus, while it was not amplified from cDNA of the patient. In the I gamma 1 region of LCL cultured with SAC plus rIL-2, the inner cytosine in the 5' C-C-G-G 3' sequence nearest the 3' site of the I gamma 1 region, at least, was not completely unmethylated in the patient. Moreover, the DNase I hypersensitive site was not induced in the patient's LCL by SAC plus rIL-2. These results indicate that the defects of the immunoglobulin heavy chain isotype switch in the patient's B cells are due to failure in the synthesis of germ-line C gamma transcripts, and this may be caused by defects in opening of the chromatin structures of specific switch regions.

Adolescent↗
PubMed1995

Medullary TRH is involved in gastric protection induced by low dose of kainic acid into the raphe pallidus.

The gastroprotective effect of kainic acid microinjected into the raphe pallidus (Rpa) at a dose subthreshold to increase acid secretion was investigated in urethan-anesthetized rats. Kainic acid (25 pg/30 nl) microinjected into the Rpa inhibited by 65.8% gastric damage induced by intragastric ethanol (60%). No protection was observed when kainic acid was injected outside of the Rpa. The cytoprotective effect was completely abolished by thyrotropin-releasing hormone (TRH) antibody microinjected bilaterally (1.3 micrograms/site) into the dorsal motor nucleus of the vagus (DMN), indomethacin (5 mg/kg ip), and atropine (0.3 mg/kg sc). Microinjection of TRH antibody outside of the DMN or of control antibody into the DMN did not modify the protective action induced by kainic acid into the Rpa. The TRH antibody microinjected alone into the DMN did not alter the severity of the ethanol-induced gastric lesions. These data indicate that excitation of Rpa neurons by a low dose of kainic acid results in cytoprotection against ethanol lesions. Furthermore, this cytoprotection occurs as a result of TRH action in the DMN and activation of muscarinic and prostaglandin pathways.

Animals↗
PubMed1995

[An analysis of 41 elderly patients with urosepsis].

We performed a clinical evaluation in 41 patients with urosepsis at Tokyo Metropolitan Geriatric Hospital from July 1992 through March 1993. The most common organism isolated from the patients was Escherichia coli (46.3%), followed by Pseudomonas aeruginosa (9.8%), Methicillin-resistant staphylococcus aureus (7.3%), and mycetes (7.3%). The most frequent underlying disease was cerebrovascular disease (34.1%) and malignancies were observed 29.2% of all cases. Twenty-six patients (63.4%) had indwelling urethral catheters. Indwelling catheters were suspected to be related to the onset of urosepsis in 16 cases. Total mortality of urosepsis was 4.9% (2/41) in this study. We speculate that the main cause of urosepsis is a long-term use of urethral catheterization, especially in elderly patients with severe complications who are vulnerable to infections. It is important to assess and correct the conditions of dysuria of individual patients before placing indwelling urethral catheters.

Aged↗
PubMed1995

[A combined consecutive therapy with fosfomycin and sulbactam/cefoperazone for bacterial infections associated with hematological diseases].

A combination antibacterial therapy with fosfomycin (FOM) and sulbactam/cefoperazone (SBT/CPZ) was applied to 78 patients with severe infections associated with hematological diseases. In this protocol, FOM was followed by SBT/CPZ and each drug was administered for 1 hour intravenously and consecutively. Among 72 evaluable patients, 43 patients had acute leukemia, myeloblastic or lymphoblastic, 22 had malignant lymphoma, 3 had multiple myeloma, and 4 had other hematological diseases as underlying diseases. Bacterial infections diagnosed were sepsis in 21 patients, suspected sepsis in 47, and other infections in 4. The overall efficacy rate of this treatment was 72.2%, and those for individual infections were 66.7% for sepsis, 74.5% for suspected sepsis, and 75.0% for other infectious diseases. Among 22 bacteria separated from patients with sepsis, 78.6% (11/14 strains) were eradicated by this treatment. This protocol was also effective in 57.1% (8/14) of patients whose granulocyte count was less than 100/mm3 during the course of treatment as well as in 83.3% (15/18) of patients with granulocyte count over 500/mm3. There was no difference in effectiveness between those patients to whom G-CSF was administered and those to whom it was not (17/24, 70.8% vs 35/48, 72.9%). As an adverse reaction, a transient increase of GOT and/or GPT was observed in 2 patients (2.8%). The consecutive administration treatment of FOM and SBT/CPZ is thus an effective and safe regimen for the treatment of patients with hematological diseases complicated by severe infections.

Adult↗