Biomedical subjects

H Kaneko

Publications and source records attributed to H Kaneko.

At least 307 records · Page 17Linked to original sources

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

Successful steroid withdrawal half a year after kidney transplantation.

We report two kidney transplant recipients with successful steroid withdrawal. They are living related donor transplant recipients. The first patient, a 37-year-old female, received the kidney from her HLA identical father. The second patient, a 44-year-old man, received the kidney from his HLA 1 haploidentical brother. Both patients were maintained on triple immunosuppressive drug therapy prior to withdrawal of steroid and subsequently were maintained on cyclosporine and azathioprine or mizoribine. Acute rejection occurred within the first 1 month and was treated with steroid bolus therapy successfully in both cases. The time of steroid withdrawal after transplantation was 6.5 months in the first patient and 5 months in the second patient. After steroid withdrawal their graft function remained stable and the graft specimens obtained by biopsy 8 months after withdrawal showed no signs of rejection; no side effects of steroid appeared. These results suggest that steroid withdrawal half a year after transplantation can be accomplished without jeopardizing graft function in selected living related donor transplant recipients.

Adult↗

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

Pyrethroids, nerve poisons: how their risks to human health should be assessed.

The extensive worldwide efforts of structural modification of natural pyrethrins for better performances have resulted in successful development of a wide variety of synthetic pyrethroids with tremendously high efficacy, knock-down activity or vapor action, and/or with acceptable environmental stability and safety. Currently these pyrethroids including their preferentially manufactured stereoisomers are widely used in agriculture, and for public health as well as household insect control. The detailed toxicology and metabolism studies intended to attain human risk assessment have revealed that with voltage-dependent sodium channel as target site pyrethroids induce pronounced repetitive activity characterized grossly by tremor, hypersensitivity, choleoathetosis, and salivation. In addition, so-called cyano-pyrethroids cause transient skin paresthesia in workers. With regard to tumorigenicity, mutagenicity, teratogenicity and developmental toxicity, no significant findings have been reported. Pyrethroids are eliminated from the animals quite rapidly and completely, undergoing oxidation and ester hydrolysis followed by various conjugations, with low tissue residues. Thus, overall, sound scientific bases exist for human risk assessment under the present usage conditions.

Animals↗

PubMed1995

A new adenosine subtype-1 receptor antagonist, FK-838, attenuates salt-induced hypertension in Dahl salt-sensitive rats.

We investigated the effects of the adenosine type-1 receptor antagonist FK-838 on salt-induced hypertension in Dahl-Sea salt-sensitive (Dahl S) rats. Dahl S rats fed a high-salt (4% NaCl) diet for 4 weeks were treated with FK-838 or hydrochlorothiazide for 4 weeks and alterations in kidney function and morphologic changes were assessed. FK-838 attenuated the development of hypertension in Dahl S rats, and caused a decrease in aortic weight in a dose dependent fashion. The adenosine antagonist did not produce any detectable metabolic disturbance. The blood pressure reduction by FK-838 was associated with attenuation of glomerular and arterial injury in the kidney. The renal protective effect of FK-838 treatment was associated with a reduction of plasma renin activity and plasma aldosterone concentration. In contrast, the thiazide diuretic, which produced almost the same blood pressure reduction as FK-838, did not attenuate renal damage. These data indicate that adenosine A1 receptor antagonism reduces salt-induced hypertension and the consequent renal injuries.

Animals↗

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

Double mutations of the N-ras gene in a patient with acute myelomonocytic leukemia.

We report a patient with acute myelomonocytic leukemia (AMMoL) who showed two independent point mutations of the N-ras gene at codons 12 and 13. Longitudinal analysis revealed that one mutation at codon 13 was detectable throughout his disease course and the other at codon 12 emerged as a second mutation 14 months after the diagnosis was made, at the refractory stage. Cloning to vector and subsequent sequencing confirmed that these mutations occurred in different alleles. Chromosome findings showed a simple abnormal karyotype at presentation and further karyotypic aberrations during his disease course, concomitantly with the second mutation of the N-ras gene. These findings revealed a close relationship among the disease progression, karyotypic evolution and a newly-appearing N-ras mutation.

Aclarubicin↗

PubMed1995

Novel monoclonal antibody reactive with thrombin-sensitive 74-kDa glycoproteins present on platelets and megakaryocytes both from mouse and rat.

A monoclonal antibody (designated 1C2) that reacts only with mouse platelets and megakaryocytes among hematopoietic cells was established by immunizing mouse platelets to an Armenian hamster. 1C2 reactive mouse molecule (1C2 antigen) was a surface glycoprotein with molecular weight of 74 kDa. Side by side comparison revealed that 4A5, a rat monoclonal antibody against mouse platelet, immunoprecipitated the identical molecule to 1C2 antigen. Of particular interest, 1C2 also labeled rat tissues with an identical pattern to that of mouse tissues and recognized a 74-kDa protein from rat platelets. Reactivity of 1C2 to mouse and rat platelets decreased when they were treated with thrombin. Following thrombin treatment of mouse platelets, 1C2 reactive 69-kDa protein appeared in the supernatants. Mouse and rat 1C2 antigens purified on 1C2-coated beads were cleaved by thrombin to generate 69-kDa fragments, establishing that 1C2 antigen is a direct substrate for thrombin. 1C2 is the first antibody to platelets and megakaryocytes of mouse and rat whose reactive molecule is well characterized, i.e., substrate for thrombin. 1C2 can be a useful tool in studying megakaryocytopoiesis and thrombopoiesis in rodent systems.

Animals↗

PubMed1995

Immunoneutralization of inhibin and estradiol during the follicular phase of the estrous cycle in cows.

To investigate the physiological importance of inhibin and estradiol in the regulation of FSH secretion during the follicular phase of the estrous-cycle in cows, animals were passively immunized against the two hormones. Sixteen cows were divided into four equal groups and given injections of prostaglandin F2 alpha (PG) i.m. twice at 8-h intervals on Day 10 of the estrous cycle (Day 0 = day of estrus) to induce luteal regression. At 48 h after the first PG injection, each group of four cows received injections of one of the following: 100 ml castrated goat serum (control serum), 100 ml antiserum against inhibin, 100 ml antiserum against estradiol, or a combination of 100 ml inhibin antiserum and 100 ml estradiol antiserum. The LH surge occurred within 2 days after injection of the control serum or inhibin antiserum, whereas it was not detected in either of the groups passively immunized against estradiol, indicating that passive immunization against estradiol blocks a positive feedback effect of estradiol on LH secretion. There was no clear difference in basal concentrations of LH among the four groups. Injection of the inhibin antiserum resulted in a marked increase (p < 0.01) in plasma concentrations of FSH compared with values in the control group, while there were no significant changes in concentrations of plasma FSH after injection of the estradiol antiserum. Combined administration of the inhibin and estradiol antisera also produced a marked increase (p < 0.01) in plasma concentrations of FSH. The FSH response to the combined immunization was longer in duration than the FSH response to immunization with inhibin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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

Non-phenotypic detection of osteopetrotic (op/op) mutation by using PCR-SSCP analysis.

Mice homozygous for recessive mutation osteopetrosis (op/op) on chromosome 3 provide a unique model to study the mechanism of haematopoiesis in conjunction with bone formation. Based on the DNA sequence data recently reported, we established a PCR-SSCP (polymerase chain reaction--single strand conformation polymorphism) assay which identifies an amplified fragment having an insertional point mutation present in macrophage colony-stimulating factor (M-CSF) gene of op/op mice. With this assay, three genotypes, op/op, +/op, and +/+ can be distinguished. Although heterozygous (+/op) and normal (+/+) mice could not be discriminated phenotypically, we could generate op/op mutant mice starting from a single heterozygous (+/op) mouse using only the PCR-SSCP aided screening method. This assay will permit introduction of the op mutant into any strain to generate a new animal model to study the cytokine network and haematopoiesis.

Animals↗

PubMed1995

In vitro reactions of coelomocytes against sheep red blood cells in the solitary ascidian Halocynthia roretzi.

Coelomocytes (blood cells) of the solitary ascidian Halocynthia roretzi were placed in culture to which sheep red blood cells (SRBCs) were introduced. Their reactions against SRBCs were observed by phase-contrast, time-lapse video and scanning electron microscopy. Three cell types, the phago-amoebocyte, the vacuolated cell and the fusogenic phagocyte, reacted to the SRBCs by phagocytosis. The vacuolated cell occasionally discharged the material of their vacuoles at the time of or shortly after ingesting the SRBC. The lymphoid cell captured SRBCs, but did not ingest them. Three other cell types, the fibroblastic cell, the giant cell and the multipolar cell, showed no reaction to the SRBC. The SRBCs captured by the lymphoid cells were transferred either to phago-amoebocytes or fusogenic phagocytes, probably to be ingested. Such collaboration between multifunctional cell is considered to characterize the cellular defense mechanism of H. roretzi.

Animals↗

PubMed1995

Metabolism of Cyanox in the rat. I. Absorption, disposition, excretion and biotransformation.

1. To examine the metabolic fate of Cyanox [O-4-cyanophenyl O, O-dimethyl phosphorothioate, cyanophos, CYAP], rats of both sexes were administered [phenyl-4C]Cyanox as a single oral dose at levels of 0.5 mg/kg (low-dose group) or 25 mg/kg (high-dose group), or as multiple doses at 50 mg/kg/day once daily for 7 days (repeat-dose group). 2. The radiocarbon was almost completely eliminated from rats within 7 days after administration in both low- and high-dose groups. 14C-recoveries (expressed as % relative to the dosed 14C) in faeces and urine were 2-3 and 95-96% respectively for the low-dose and 13-14 and 86% respectively for the high-dose. 3. 14C-tissue residues on the seventh day after a single administration were generally low. Peak 14C-concentrations in blood and kidney occurred at 0.5 h (high-dose) and decreased rapidly thereafter. 4. Sex-related differences in the amounts of metabolites were observed in both groups. With the low-dose, the major metabolite was 4-cyanophenylsulphate in both sexes. However, in the high-dose, the major metabolites were 4-cyanophenyl sulphate and desmethylcyanoxon in males, but 4-cyanophenyl sulphate and desmethylcyanox in females. These findings indicate that the amounts or the types of enzymes responsible for oxidative desulphuration or oxidative dearylation in males are different from those in females. In the male rat given repeat doses significant differences in the amounts of metabolites in excreta were observed between early and final dosing. 5. The greater formation of desmethylcyanoxon in the male rat in the high-dose case is consistent with the higher incidence of toxicity in this sex.

Absorption↗