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Biomedical subjects

K Nishino

Publications and source records attributed to K Nishino.

At least 19 recordsLinked to original sources

[Clinical significance of serum neuron-specific enolase in non-small cell lung cancer].

The present study was a retrospective analysis of serum neuron-specific enolase (NSE) assayed in 302 patients with non-small cell lung cancer (NSCLC) before treatment. Serum NSE ranged from 0.6 to 183.0 ng/ml, with a mean value of 12.2 ng/ml, and exceeded 10 ng/ml in 145 patients (48.0%). The mean levels and rate of NSE positivity in 177 patients whose tumors were categorized as small, medium and large (from the product of the maximum and perpendicular axis of the tumor on chest X-ray), were highest in the large group. There was no significant relationship between serum NSE and the response rate to anticancer chemotherapy. The survival period of the patients with elevated serum NSE (median, 5.7 months) was significantly shorter, than those with normal serum NSE levels (median, 12.1 months). Serum NSE is of prognostic significance in a multivariate analysis (p < 0.01), but not predictive of response to chemotherapy in NSCLC.

Aged

[Clinical evaluation of a reagent for detection of DNA of Mycobacterium tuberculosis complex using the ligase chain reaction (LCR) method].

We evaluated the clinical efficacy of LCR MTB, a reagent developed by Abbott in the USA, in the full automatic ligase chain reaction (LCR) for detection of DNA of M. tuberculosis complex using a thermostable ligase. Using 458 samples isolated from patients with tuberculosis, LCR was compared with a smear method and with a culture method, and was also compared with two other methods of gene amplification, MTD and Amplicor, using 340 and 200 of the 458 samples, respectively. The LCR method detected M. tuberculosis in 49.8% (228/458) of the samples, and was superior to the smear method (31.9%, 146/458) and the culture method (39.1%, 179/458) in sensitivity. The LCR method was also superior to the MTD and Amplicor methods; sensitivity were 37.9% (129/340) for MTD vs. 47.6% (162/340) for LCR, and 56.5% (113/200) for Amplicor vs. 59.5% (119/200) for LCR. These favorable results and the convenience of the LCR method, which enables rapid detection of target genes with a high degree of sensitivity, strongly suggest that LCR MTB is useful as a reagent for detection of M. tuberculosis using nucleic acid amplification.

Adolescent

Weight reduction regresses left ventricular mass regardless of blood pressure level in obese subjects.

The effects of weight reduction on left ventricular mass in obese normotensive and hypertensive subjects were investigated. Previous studies have shown that weight reduction in hypertensive (HT) obese patients is associated with decreased left ventricular mass (LVM) and decreased blood pressure (BP). This study was performed to examine whether weight reduction would also regress LVM in normotensive (NT) obese subjects and to clarify the mechanisms of these effects if they occurred. A weight-reduction program consisted of mild exercise and mild hypocaloric intake. M-mode echocardiography was performed to estimate the LVM. After the 12-week intervention, the mean reductions in body weight (BW) in the NT (n = 11) and HT (n = 11) groups were 4.9 kg (p < 0.005) and 4.6 kg (p < 0.0005), respectively. Systolic, diastolic, and mean BP were significantly reduced by 13, 9, and 11 mm Hg, respectively, in the HT group. By contrast, no significant changes in systolic, diastolic, or mean BP were observed in the NT group. LVM was significantly reduced from 176 +/- 26 gm to 159 +/- 26 gm (p < 0.05) in the HT group and from 167 +/- 33 gm to 145 +/- 34 gm (p < 0.02) in the NT group. These results suggest that weight reduction in obese subjects by mild exercise and mild hypocaloric intake can lead to a reduction in LVM, regardless of whether the subjects have normal or high blood pressure.

Adult

Effects of bilateral orbital decompression by an endoscopic endonasal approach in dysthyroid orbitopathy.

AIMS: The efficacy of endoscopic endonasal orbital decompression in dysthyroid orbitopathy was analysed. METHODS: In 21 consecutive cases of bilateral operation short term (10 (SD 6) days after operation) and long term (156 (12) days after operation) results were recorded. RESULTS: Short term results showed that vision of the more affected eye improved from a mean of 0.35 to 0.59; vision improved in all but one eye which remained unchanged. In the fellow eyes mean visual acuity improved from 0.6 to 0.7; three of these eyes showed a decrease. Mean proptosis returned from 23.0 mm to 20.0 mm. As to motility the mean abductive capacity decreased from 5.5 mm to 4.0 mm of monocular excursion, whereas adduction increased from 7.5 mm to 8.5 mm. Upgaze and downgaze did not show any major change. The mean angle of horizontal squint shifted from 7.5 degrees of convergence to 15.5 degrees while no significant vertical or cyclorotational deviation was induced. These immediate postoperative results proved to be stable for the period of long term follow up with only slight changes. No significant bleeding or specific otorhinolaryngological complication without resolve occurred intraoperatively or perioperatively. CONCLUSION: This method is believed to be superior to non-endoscopic techniques because it avoids external scars and antral pain. With regard to the relief of intraorbital pressure, the technique gives good results for visual acuity improvement, but in proptosis reduction the method is not as efficient as external or combined procedures. There seems to be no difference when compared with other approaches in induction of horizontal squint. The method has a protective long term effect against the recurrence of compressive optic neuropathy.

Adult

[Antibiotic resistance of clinical isolates Streptococcus pneumoniae].

Streptococcus pneumoniae is a major pathogenic organism of community-acquired bacterial pneumonia as well as otitis media and bacterial meningitis. Recently penicillin- or multiply resistant pneumococci have been isolated worldwide. In this study we examined the susceptibility tests of 11 antibiotics with the total of 63 clinically isolated pneumococci, using a broth microdilution method. Most of pneumococci were isolated from respiratory specimens. According to NCCLS standard, all these pneumococci were classified as follows: PCG-susceptible S. pneumoniae (PSSP, MIC < or = 0.06 micrograms/ml), PCG-intermediately resistant S. pneumoniae (PISP, 0.12 < or = MIC < or = 1.0 micrograms/ml), and PCG-highly resistant S. pneumoniae (PRSP, MIC > or = 2.0 micrograms/ml) were 45 (71.4%), 14 (22.2%) and 4 isolates (6.4%), respectively. Forty-four percent of isolates from children under 10 years and 29% from outpatients were PISP or PRSP. Resistance to erythromycin (EM) clindamycin (CLDM) or minocycline (MINO) was significantly recognized, but not correlated with that to PCG. On the other hand, the resistance to beta-lactam antibiotics were correlated with that to PCG. Seventeen isolates (27%) were resistant to two or more antibiotics among PCG, EM, MINO, ofloxacin (OFLX), and sulfamethoxazole-trimethoprim (ST). In pneumococcal infection, we always have to pay a careful attention to susceptibility test before we choose antibiotics.

Anti-Bacterial Agents

Metal-mediated oxidative damage to cellular and isolated DNA by certain tryptophan metabolites.

The tryptophan metabolites 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxykynurenine (3-HKyn) are carcinogens. DNA damage by 3-HAA and 3-HKyn in the presence of metal ions was investigated as a potential mechanism of their carcinogenicity. Pulsed field gel electrophoresis showed that in the presence of Mn(II), 3-HAA and 3-HKyn induced DNA double-strand breaks in cultured human cells. DNA single-strand breaks were observed with alkali treatment. The enhancing effect of catalase inhibitor and the inhibitory effect of o-phenanthroline on the strand breakage indicated the involvement of H2O2 and endogenous transition metal ion. Damage to DNA fragments obtained from c-Ha-rds-1 protooncogene was investigated by a DNA sequencing technique. 3-HAA and 3-HKyn induced piperidine-labile sites frequently at thymine and guanine residues in the presence of Cu(II). The inhibitory effects of bathocuproine and catalase on Cu(II)-mediated DNA damage suggest that Cu(I) and H2O2 have important roles in the production of active species causing DNA damage. The Cu(II)-mediated DNA damage was enhanced by preincubation of 3-HAA with Mn(II). UV-visible spectroscopy showed that Mn(II) and Cu(II) enhanced the rate of autoxidation of 3-HAA in different ways. These results suggest that in the presence of Mn(II) or Cu(II), these tryptophan metabolites produce H2O2, which is activated by transition metal ion to cause damage to DNA both in the case of isolated DNA and cultured cells.

3-Hydroxyanthranilic Acid

Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy. Evidence for brain natriuretic peptide as an "emergency" cardiac hormone against ventricular overload.

We previously demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone mainly produced in the ventricle, while the major production site of atrial natriuretic peptide (ANP) is the atrium. To assess the pathophysiological role of BNP in ventricular overload, we have examined the gene expression of BNP, In comparison with that of ANP, in a model of cardiac hypertrophy using cultured neonatal rat ventricular cardiocytes. During cardiocyte hypertrophy evoked by endothelin-1, Phenylephrine, or PMA, the steady state level of BNP mRNA increased as rapidly as the "immediate-early" induction of the c-fos gene expression, and reached a maximal level within 1 h. Actinomycin D, a transcriptional inhibitor, completely diminished the response, while the translational blocked with cycloheximide did not inhibit it. In contrast, ANP mRNA began to increase 3 h after the stimulation, and accumulated during cardiocyte hypertrophy. The BNP secretion from ventricular cardiocytes was also stimulated, more rapidly than the ANP secretion. Furthermore, the turnover of BNP mRNA was significantly faster than that of ANP mRNA, being consistent with the existence of AUUUA motif in the 3'-untranslated region of BNP mRNA. These results demonstrate that the gene expression of BNP is distinctly regulated from that of ANP at transcriptional and posttranscriptional levels, and indicate that the characteristics of the BNP gene expression are suitable for its possible role as an " emergency" cardiac hormone against ventricular overload.

Animals

[A case of cutaneous malignant melanoma metastatic to the choroid].

A case of metastasis of cutaneous malignant melanoma to the choroid was reported. The patient, a 61-year-old man, had undergone an amputation of his right first finger 3 years ago due to cutaneous malignant melanoma. Ophthalmoscopic examination revealed a whitish yellow elevated choroidal lesion and serous retinal detachment in the left eye. Fluorescein angiography demonstrated multiple pinpoint leaks in the early phase and progressive pooling of dye into the subretinal space in the late phase. In magnetic resonance imaging, the tumor showed a hyperintense image in both T1 and T2-weighted images. Autopsy was performed and histopathological examination of the eye showed that the tumor cells were polygonal in shape, and had round or oval nuclei, but the cytoplasms had little melanin pigment. Immunohistochemistry for S-100 and HMB-45 antibody showed positive staining in choroidal tumor and other metastatic lesions, indicating that they were metastatic tumors from cutaneous malignant melanoma (amelanotic melanoma cells).

Choroid Neoplasms

Hydroxyl radical generation in skeletal muscle atrophied by immobilization.

Male Wistar rats (15 weeks old), the ankle joints of one hindlimb of which were immobilized in the extended position for 12 days, were injected with salicylate as a trapping agent for hydroxyl radicals before sacrifice. Atrophied and contralateral soleus, typical slow red muscles were collected and their levels of 2,3-dihydroxybenzoic acid (2,3-DHB), one of the main reaction products formed by the attack of hydroxyl radical on salicylate, were determined using high-performance liquid chromatography with an electrochemical detector. There was a significant increase in 2,3-DHB in the atrophied muscle. This result strongly suggests the enhanced generation in vivo of hydroxyl radicals in atrophied muscle.

Animals

Amino acid sequence of an inhibitor from the silkworm (Bombyx mori) hemolymph against fungal protease.

A novel protein protease inhibitor (FPI-F) which is highly specific for fungal proteases and subtilisin was isolated from the silkworm hemolymph, and its amino acid sequence was determined by conventional methods. The inhibitor consisted of 55 amino acid residues and had a molecular weight of 6,100. The inhibitor included eight cysteine residues and relatively large amounts of acidic amino acids, but neither alanine, methionine nor tryptophan. The amino acid sequence of FPI-F was not homologous with those of other known protease inhibitors of microbe, plant or animal origin.

Amino Acid Sequence

Analysis of cytoplasmic and surface antigens in childhood T-cell acute lymphoblastic leukaemias: clinical relevance of cytoplasmic TCR beta chain expression.

Expression of surface and cytoplasmic antigens on the blasts from 42 cases of childhood T-cell acute lymphoblastic leukaemia (T-ALL) were analysed. All with childhood T-ALL, except for one case expressing cytoplasmic TCR delta chain, were classified on the basis of differential expression of cytoplasmic CD3 (cCD3), TCR beta chain (cTCR beta) and surface CD3 (sCD3) into the following three groups: group I (cCD3+, cTCR beta-, sCD3-), eight cases (19.5%); group II (cCD3+, cTCR beta +, sCD3-), 23 cases (56.1%); group III (cCD3+, cTCR beta +/-, sCD3+), 10 cases (24.4%). Each group defines the stepwise maturational stage of the CD3/TCR complex along the intrathymic T-cell differentiation. Group I had the lowest initial WBC count among the three groups (P < 0.05) and showed significantly (P < 0.05) a higher event-free survival (0.75) than those of group II (0.33). There was no significant difference in both the initial WBC count and the event-free survival between groups II and III. Thus, the absence of cTCR beta in sCD3-negative T-ALL appears to be a good prognostic factor, suggesting that this classification provides a useful tool to predict the prognosis of childhood T-ALL. This is the first report, to our knowledge, studying the relationship between the expression of cytoplasmic CD3/TCR antigens and the clinical features in T-ALL.

Adolescent

Effect of ibudilast, a novel antiasthmatic agent, on anaphylactic bronchoconstriction: predominant involvement of endogenous slow reacting substance of anaphylaxis.

The effect of ibudilast on anaphylactic bronchoconstriction was studied in guinea pigs sensitized actively with ovalbumin (OA). Animals were treated with indomethacin, tripelennamine and propranolol prior to the antigen challenge. Anaphylactic bronchoconstriction was prevented by ibudilast (1-4 mg/kg i.v. and 5-20 mg/kg p.o.) dose-dependently. FPL55712 and phenidone were also effective. Even when administered at the maximum development of bronchoconstriction, ibudilast (0.5 and 2 mg/kg i.v.) and FPL 55712 caused significant reduction of the increased airway tone, while phenidone did not. Ibudilast (1-4 mg/kg i.v.) and FPL55712 inhibited leukotriene D4-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol. Ibudilast (1.6 and 4 mg/kg i.v.) inhibited platelet-activating-factor (PAF)-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol, however, FPL 55712 inhibited PAF-induced airway responses only at a high dose such as 10 mg/kg i.v. Ibudilast (4 mg/kg i.v.) did not inhibit acetylcholine-induced airway response. Ibudilast showed inhibition of the release of slow-reacting substance of anaphylaxis (SRS-A) from guinea pig chopped lung sensitized with OA, which was significantly diminished by indomethacin. The drug little affected the activity of phospholipase A2 and 5-lipoxygenase in guinea pig polymorphonuclear leukocytes. These results indicate that ibudilast inhibits anaphylactic bronchoconstriction which is considered to be largely mediated by endogenously released SRS-A. The inhibitory effect of ibudilast on anaphylactic bronchoconstriction in the presence of indomethacin is considered to be exerted through its antagonism to SRS-A.

Acetylcholine

Effects of the new histamine H2-receptor antagonist N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl] urea with potent gastric mucosal protective activity on acute gastric lesions and duodenal ulcers in rats.

The effects of KU-1257 (N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl]urea, CAS 120958-90-9) on gastric lesions and duodenal ulcers in rats were compared with those of various antiulcer drugs. KU-1257 prevented the formation of gastric lesions induced by necrotizing agents. The ID50 values against 0.6 N HCl-induced gastric lesions were 18.6 mg/kg, p.o. and 6.0 mg/kg, i.p. The ID50 values against absolute ethanol- and 1% NH3-induced gastric lesions were 12.4 and 9.2 mg/kg, p.o., respectively. Roxatidine acetate, troxipide and teprenone at doses of 100-200 mg/kg p.o. also significantly prevented the formation of gastric lesions by these necrotizing agents. Cimetidine, ranitidine and famotidine had no protective effect against these gastric lesions even at a dose of 200 mg/kg p.o. KU-1257, roxatidine acetate and famotidine inhibited acetylsalicylic acid- and water-immersion stress-induced gastric lesions. KU-1257, roxatidine acetate and famotidine inhibited mepirizole-induced duodenal ulcers, but not troxipide and teprenone. These results suggest that KU-1257 is more potent in the mucosal protective action than troxipide, teprenone, roxatidine acetate and other histamine H2-receptor antagonists.

Animals

Healing-promoting action of the new histamine H2-receptor antagonist N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl]urea with dual action on chronic gastric and duodenal ulcers induced by acetic acid in rats.

Healing-promoting actions of KU-1257 (N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl]urea, CAS 120958-90-9) were investigated in chronic gastric and duodenal ulcer models induced by acetic acid in rats and the effects were compared with those of famotidine and roxatidine acetate by gross or histological evaluation. KU-1257 markedly promoted the well-balanced healing of gastric ulcer at oral doses of 10-50 mg/kg x 2/day, as evidenced by the reduction of ulcer, regeneration of mucosa and proliferation of connective tissue. KU-1257 caused an increase in gastric mucus secretion in the regenerated mucosa around the gastric ulcers. Famotidine and roxatidine acetate failed to promote the healing of gastric ulcers even at 100 mg/kg x 2/day p.o. KU-1257 also significantly accelerated the healing of acetic acid-induced duodenal ulcers as well as famotidine and roxatidine acetate. These results indicate that KU-1257 is characterized by a potent promoting action on the healing of chronic ulcers, suggesting that the increase in gastric mucus secretion might be associated with the antiulcer actions of KU-1257 in part.

Acetates

Synthesis and antiulcer activity of N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas: histamine H2-receptor antagonists with a potent mucosal protective activity.

As an aim toward developing new antiulcer agents, new N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas were synthesized and evaluated for histamine H2-receptor antagonistic, gastric antisecretory, and gastric mucosal protective activities. A QSAR study showed that the most favorable N-substituents were electron-donating straight-chain alkyl groups of short length such as ethyl group from the viewpoint of dual action, i.e., gastric antisecretory and mucosal protective actions. Among the ureas studied, compounds 4, 5, and 8-10 were selected as candidates for further study.

Animals

Immunohistochemical demonstration of a new thiamine diphosphate-binding protein in the rat digestive tract.

We purified a new thiamine diphosphate-binding protein (ThDP-BP), produced an antiserum against it, and examined its immunohistochemical distribution in the rat gastrointestinal tract using the avidin-biotin complex method. Positive staining for ThDP-BP was found in the epithelial glands of the stomach, small intestine and large intestine, and in the nuclei of hepatocytes. Measurement of the content of thiamine and its phosphate esters in extracts from the gastric and intestinal mucosa also indicated the presence of ThDP-BP in the stomach and intestinal mucosa. ThDP-BP may be useful for investigating the absorption and metabolism of the thiamine in metabolic disorders.

Animals

Blood levels and urinary excretion of thiamin and riboflavin during oral administration of multivitamin tablets to healthy adults.

1. The baseline blood thiamin concentration increased gradually during the long-term administration of TTFD, and the blood concentration was dose-dependent. The cumulative urinary thiamin excretion showed the same dose-dependence as the blood concentration. 2. The baseline blood riboflavin concentration also increased steadily during the administration period, but the increase was less than that of thiamin. Dose-dependence of the cumulative urinary excretion of riboflavin was noted. 3. No side effect were observed.

Administration, Oral