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Biomedical subjects

H Kaneko

Publications and source records attributed to H Kaneko.

At least 325 records · Page 18Linked to original sources

Species and sex differences of testosterone and nifedipine oxidation in liver microsomes of rat, dog and monkey.

1. Species and sex differences in testosterone hydroxylation and nifedipine oxidation in liver microsomes from rat, dog and monkey have been investigated. 2. The formation of 2 alpha-, 2 beta-, 6 beta-, and 16 alpha-hydroxytestosterone and androstenedione in the male rat was higher than that in the female rat. Microsomes prepared from the male rat oxidized nifedipine about eight times faster than did those from the female rat. In contrast, marked sex-related differences were not seen in the dog and monkey. 3. Nifedipine oxidase activity in rat, dog and monkey correlated significantly with the activities for both testosterone 2 beta-hydroxylation and 6 beta-hydroxylation, suggesting the involvement of P4503A isozymes in these reactions. The ratios of formation of the 2 beta- to 6 beta-hydroxytestosterone in male rat and monkey were 0.17 and 0.18 respectively, whereas that in dog was 0.46. The corresponding activity ratios catalysed by P450DPB-1, a P4503A isoform purified from dog liver microsomes, was 0.36. 4. The formation of 16 beta-hydroxytestosterone was higher than that of the 16 alpha-hydrolated metabolite in liver microsomes from monkey, whereas 16 alpha-hydroxytestosterone was the predominant metabolite in the rat and dog, indicating species differences in stereoselectivity at the 16-position.

Animals↗

[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↗

[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↗

Possibility of postprandial electrogastrography for evaluating vagal/nonvagal cholinergic activity in humans, through simultaneous analysis of postprandial heart rate variability and serum immunoreactive hormone levels.

OBJECTIVES: To investigate changes in postprandial electrogastrography (EGG) from the neurohormonal mechanisms. METHODS: We measured EGG indices [frequency amplitude of normal 3-cpm (EGG-3 cpm)], high frequency amplitude of heart rate variability which has reflected cardiac parasympathetic tone, and several serum immunoreactive (ir)-hormone levels in 12 fasted male volunteers (mean age 25.3 yr). RESULTS: Immediately after the liquid food intake (250 kcal), a transient decrease in EGG-3 cpm frequency (from 0.045 +/- 0.001 Hz to 0.040 +/- 0.001 Hz; p < 0.05) accompanied by an increase in high frequency amplitude (from 31.05 +/- 3.45 ms to 39.10 +/- 4.08 ms; p < 0.05), and a serum immunoreactive gastrin level increase (from 38.72 +/- 4.92 pmol/L to 54.00 +/- 10.45 pmol/L; p < 0.05) and an immunoreactive somatostatin level decrease (from 15.00 +/- 0.43 pmol/L to 13.70 +/- 0.46 pmol/L; p < 0.01) were observed, suggesting vagal excitement. EGG-3 cpm amplitude and serum immunoreactive human pancreatic polypeptide (hPP) levels significantly increased soon after ingestion, and these changes lasted for 30 min. Furthermore, there was a positive correlation between changes in EGG-3 cpm amplitude and those in serum immunoreactive hPP levels during the postprandial periods (r = 0.55, p < 0.001). CONCLUSIONS: Considering the reports that a cholinergic, nonvagal pathway is of major importance in food-stimulated hPP release, the present results suggest that postprandial changes in EGG-3 cpm frequency and amplitude might be a good tool for evaluating not only vagal but also nonvagal cholinergic activity in the human gut.

Adult↗

[Combination chemotherapy with FP versus FEP in patients with advanced gastric cancer. Research group of gastric cancer chemotherapy].

Forty-eight patients with unresectable gastric cancer were enrolled for a randomized trial of FP (n = 24) vs FEP (n = 24) combination chemotherapy with respect to their effects on survival period. Of these, excluding 7 patients, 21 in FP group were treated with 400 mg/m2 UFT po daily and 50 mg/m2 CDDP i.v. on days 1 and 8 every 4 weeks, and 20 in FEP group were treated with 400 mg/m2 UFT po daily, 50 mg/m2 etoposide iv and 50 mg/m2 CDDP i.v. on days 1 and 8 every 4 weeks. In FP group, 10 PR in primary lesions were observed with an overall response rate of 52.4%. In FEP group, 5 PR in primary lesions were observed with an overall response rate of 35.0%. Toxicities over Grade 3 were anorexia (35%), vomiting (25%), and leukopenia (12%), which were manageable. The 50% survival time in FP and FEP group was 233 and 176 days, respectively. Because of the high response rate and prolongation of the survival period, combination chemotherapy with FP seemed to be useful for the treatment of patients with advanced gastric cancer.

Adenocarcinoma↗

[An immunohistochemical study on microtubule associated protein-1 of normal and malignant human gastric tissue].

Microtubule Associated Protein-1 (MAP-1) plays an important role for polymerization of tublin to microtubules. Indirect immunohistochemistry using anti-MAP-1 monoclonal antibody was performed in this study. Difference of internuclear MAP-1 staining patterns between normal and malignant human gastric tissues was investigated. Normal gastric tissue had localized MAP-1 positive staining nucleus in corresponding area of generative cell zone of gastric gland. On the other hand, the 75% cases of gastric cancer showed numerous labeled nuclei in most of the cancer tissues, and 25% cases did not show positive staining of nuclei in cancer tissue. The nuclei staining were classified as negative (-), weak granular (+) and strong punctate (++). The tissue staining pattern was fallen into two patterns, uniform and ununiform stained groups. Positive nuclei staining for MAP-1 and staining pattern had no correlation with histological type of gastric cancer, vessel invasion and lymph node metastasis. But post operative 5-years survival rares were 77.3% in uniform stained group and 30.0% in ununiform stained group. Thus, there were relationship between the post operative survival ratio and the staining pattern of nuclei. Internuclear MAP-1 staining pattern was considered to be one of effective parameters on prognostic sign in gastric cancer.

Antibodies, Monoclonal↗

Changes in urinary kallikrein excretion and plasma natriuretic factor in a patient with primary aldosteronism with special reference to adrenal histology.

High level of urinary kallikrein excretion was observed in a 23-year-old man with primary aldosteronism. Unilateral adrenalectomy improved the clinical symptoms and normalized the urinary concentration of this vasoactive substance. Although plasma atrial natriuretic factor was not elevated, adrenal surgery lowered its concentration. Coexistence of an adrenal adenoma and lesions of nodular hyperplasia were detected in the removed adrenal gland. We summarize the clinical data of this patient and review the literature.

Adrenal Cortex↗

Relative shear disparities and the perception of surface inclination.

A dichoptic display in which the images are cyclorotated in opposite directions does not appear inclined. This suggests that perceived inclination depends on the difference between horizontal-shear and vertical-shear disparity. Large random-dot stereoscopic displays were presented with various types of shear disparity. Perceived inclination was the same magnitude for horizontal and vertical shear disparities. Opposed horizontal and vertical shear produced greater inclination than a single-axis shear. Same-sign vertical and horizontal shear (rotation) produced no inclination. These results support the relative-shear hypothesis. Cyclovergence was measured and was insufficient to account for these effects. We conclude that perceived inclination depends on the difference between horizontal- and vertical-shear disparities. Perceived inclination was not based on vertical disparity within small displays or within large displays with a zero-disparity surround. Relative-shear disparities are therefore extracted globally rather than locally.

Adult↗

Biosynthesis of a novel polysaccharide by Acetobacter xylinum.

An Acetobacter xylinum adapted to a medium containing N-acetylglucosamine (GlcNAc) has been used to prepare a novel polysaccharide containing residual GlcNAc in cellulose. The maximum amount of incorporation was found to be 4 mol% in cellulose, when a mixed medium containing 1.4% glucose (Glc) and 0.6% GlcNAc was used for the culture of A. xylinum. The resulting polysaccharide was lysozyme-susceptible. The aminosugar residue incorporated into bacterial cellulose was found to be only GlcNAc, even if galactosamine (GalN) and glucosamine (GlcN) were applied, whereas there was little effect by mannosamine (ManN). As the major component of the resulting polysaccharide was Glc residues, even if the only carbon source in the culture medium was GlcNAc, it was suggested that there must be several enzyme systems to convert GlcNAc into Glc in the bacteria. Several ammonium salts were also found to be effective for the incorporation of GlcNAc residues when the incubation system was converted to rotatory and aerobic incubation from static incubation. The amount of residual GlcNAc was remarkably increased by the addition of lysozyme-susceptible phosphoryl-chitin (P-chitin) and increased slightly with addition of P-chitin that was less lysozyme-susceptible. However, little effect was found on addition of highly substituted P-chitin.

Acetylglucosamine↗

Mercury compounds induce a rapid increase in procoagulant activity of monocyte-like U937 cells.

When monocytic leukaemia line U937 cells were incubated in the presence of HgCl2 there was a rapid increase in tissue factor (TF)-dependent procoagulant activity, reaching a maximum (equivalent to the total TF activity observed when cells had been subjected to a freeze/thaw cycle) after 15 min at 50 microM HgCl2 and after 30 min at 10 microM HgCl2. Two other heavy metal compounds, AgNO3 and phenylmercuric acetate, caused a similar increase in TF activity. The increase was independent of protein synthesis. Other reagents tested, CdCl2, ZnCl2, NiCl2, ADP, FMLP and monocyte chemotactic factor (MCF-1), did not cause a rapid increase in functional activity, when tested under the same experimental conditions. The addition of HgCl2 to the cells causes, in a concentration-dependent manner, a 10-12-fold increase in intracellular calcium (Cai) which coincides with increase in TF activity. Calcium ionophore also caused an increase in TF activity of the U937 cells. Upon treatment with HgCl2 the cell surface of U937 cells showed a large increase in the level of phosphatidylserine (PS) on the cell surface (as measured by potentiation of the rate of activation of prothrombin by factor Xa-factor Va) but with no change in the level of TF antigen on the cell surface. We consider that the TF is present on the cell surface of the monocyte but relatively inactive towards the physiological substrate, factor X (FX), until HgCl2 causes a change in the polarity of the cell membrane exposing PS on the outer leaflet by a mechanism likely to be enhanced by the increase in intracellular calcium.

Blood Coagulation↗

Multiple aberrant splicing of the p53 transcript without genomic mutations around exon-intron junctions in a case of chronic myelogenous leukaemia in blast crisis: a possible novel mechanism of p53 inactivation.

We found three truncated p53 transcripts in a patient with chronic myelogenous leukaemia in blast crisis carrying chromosome 17 abnormalities. Sequencing of these transcripts revealed complete absence of the entire exons 7, 8 and 9 in one, exons 8 and 9 in another, and exon 10 in the other. Sequencing analysis of genomic DNA, however, revealed no mutation in exons 6-10 and their flanking introns. These results suggest that the aberrant p53 transcripts in this case might not result from splicing mutations but from an unknown affected splicing process.

Base Sequence↗

Intracisternal thyrotropin-releasing hormone-induced vagally mediated gastric protection against ethanol lesions: central and peripheral mechanisms.

The vagus is involved in mediating gastric cytoprotection and adaptive cytoprotection. However, the central and peripheral mechanisms through which the vagus expresses its action are still poorly known. Medullary thyrotropin-releasing hormone (TRH) plays an important role in the vagal regulation of gastric function. The stable TRH analogue, RX 77368, micro-injected into the cisterna magna or the dorsal motor nucleus (DMN) of the vagus at a dose that did not influence gastric acid secretion prevented gastric injury induced by intragastric administration of 60% ethanol in conscious or urethane-anaesthetized rats. The cytoprotective action of TRH is mediated through vagal cholinergic release of prostaglandin E2 (PGE2). Prostaglandin E2 action is unrelated to changes in gastric mucosal blood flow (GMBF). In addition, other peripheral mechanisms involve calcitonin gene-related peptide (CGRP) contained in capsaicin sensitive afferent fibres and nitric oxide, both of which mediate the associated increase in GMBF induced by intracisternal injection of RX 77368. These data indicate that medullary TRH induces vagally mediated gastric protection against ethanol lesions. Its action is expressed through the muscarinic dependent release of PGE2 and nitric oxide, and efferent function of capsaicin-sensitive afferent fibres releasing CGRP.

Animals↗

Effects of microsphere suspension agents on systemic hemodynamics in rats. Comparison of nonradioactive colored and radioactive microspheres.

The systemic hemodynamic effects of different microsphere suspension agents were evaluated in 22 Sprague-Dawley male rats. Rats were divided into three groups, and three different solutions (distilled water; n = 7, 10% dextran; n = 8, and 70% glucose; n = 7) were injected through the left atrium respectively. 0.2 ml of each solution was injected repeatedly until significant hemodynamic changes developed. During four sequential injections, distilled water had no significant effects on cardiac output, mean arterial pressure, and heart rate. However, the 10% dextran (mol wt 70,000) solution produced significant decreases in both cardiac output and mean arterial blood pressure during and after the third injection. The 70% glucose solution also decreased, cardiac output significantly during the third injection. Although microspheres itself must cause some hemodynamic changes, our results indicated that the hemodynamic disturbances observed during a large dose injection of microspheres might have been at least in part due to the use of high-density suspending solutions. The doses of radioactive microsphere solution in many previous rat studies were usually less than 0.6 ml. However, in the case of large dose injection of microspheres, these results indicate that the suspending solutions can affect hemodynamic parameters in various ways.

Animals↗

Metabolism of tetramethrin isomers in rat: II. Identification and quantitation of metabolites.

1. To examine the metabolic fate of (1RS, trans)- or (1RS, cis)-tetramethrin [3, 4, 5, 6-tetrahydrophthalimidomethyl (1RS, trans)- or (1RS, cis)-chrysanthemate], rat was administered a single oral dose of trans- or cis-[alcohol-14C]tetramethrin at dose levels of 2 or 250 mg/kg. 2. The radiocarbon was almost completely eliminated from rat within 7 days after administration in all groups. 14C-recoveries (expressed as percentages relative to the dosed 14C) in faeces and urine were 38-58 and 42-58% respectively in rat administrated trans-[alcohol-14C]tetramethrin, and in faeces and urine were 66-91 and 9-31% respectively in rat administered cis-[alcohol-14C]tetramethrin. 3. Fourteen metabolites found in excreta were purified by using several chromatographic techniques and identified by spectroanalyses (nmr and MS). Five sulphonate derivatives and three dicarboxylic acid derivatives were found. 4. The main metabolites were sulphonate derivatives in the faeces, and in the urine, alcohols, dicarboxylic acid and reduced metabolites derived from the 3,4,5,6-tetrahydrophthalimide moiety.

Animals↗

Metabolism of tetramethrin isomers in rat. I. Identification of a sulphonic acid type of conjugate and reduced metabolites.

1. Urinary and faecal metabolites in rat treated with 14C-labelled (1RS, trans)-tetramethrin [3,4,5,6-tetrahydrophthalimidomethyl (1RS, trans)-chrysanthemate] were identified using chromatographic techniques and spectroanalyses (nmr and ms). 2. 3-Hydroxy-cyclohexane-1,2-dicarboximide was found to be a major and unique urinary metabolite, reduced at the 1,2-double bond of the 3,4,5,6-tetrahydrophthalimide moiety. 3. The major faecal metabolites were sulphonic acid conjugates, having a sulphonic acid group incorporated into the double bond of the 3,4,5,6-tetrahydrophthalimide moiety. 4. On the basis of the metabolites identified here, the major biotransformation reactions of trans-tetramethrin in rats are: (1) cleavage of the ester linkage; (2) cleavage of the imide linkage; (3) hydroxylation of the cyclohexene or cyclohexane ring of the 3,4,5,6-tetrahydrophthalimide moiety; (4) oxidation at the methyl group of the isobutenyl moiety; (5) reduction at the 1,2-double bond of the 3,4,5,6-tetrahydrophthalimide moiety; and (6) incorporation of a sulphonic acid group into the 1,2-double bond of the 3,4,5,6-tetrahydrophthalimide moiety.

Animals↗

Identification of two new types of S-linked conjugates of Etoc in rat.

1. Two major metabolites of 14C-labelled (4S,1R)-trans-Etoc[(S)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1R)-trans-chrysanthemate] were purified using a combination of chromatographic techniques and identified by spectroanalysis (nmr(HMBC) and FAB-, TSP-MS). These were established as new types of S-linked conjugates (sulphonic acid and mercapturic acid types). 2. To examine the mechanism of formation of the sulphonic acid and mercapturic acid conjugates, sodium sulphate or glutathione labelled with 35S were administered to rat along with unlabelled trans-Etoc. Both sulphonic acid and mercapturic acid conjugates were found in the excreta, more of the former being yielded with 35S-sodium sulphate than with 35S-glutathione, implying that a sulphonic acid was incorporated into the double bond of a possible intermediate after reduction of sulphate to sulphite. The mercapturic acid conjugate was produced only with 35S-glutathione, implying incorporation of glutathione into the triple bond before subsequent generation of mercapturic acid from the glutathione conjugate. 3. Additional investigation of whether or not the mercapturic acid conjugate was produced by mixing the alcohol moiety of Etoc, PGL (4-hydroxy-3-methyl-2-(2-propynyl)cyclopent-2-en-1-one) and N-acetyl-L-cysteine under alkaline conditions. However, spectral data for the synthesized compound were not the same as those of the metabolite generated in vivo. That is, the addition reaction appeared to proceed by anti-Markownikov's rule, whereas the in vivo metabolite was apparently formed according to Markownikov's rule. Addition of glutathione at a triple bond has not been reported to our knowledge for any other foreign compounds in mammalian species.

Animals↗