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Biomedical subjects

K Shibata

Publications and source records attributed to K Shibata.

At least 253 records · Page 14Linked to original sources

Conversion ratio of tryptophan to niacin in rats fed a vitamin B1-free diet.

The effect of a vitamin B1-free diet on the conversion ratio of tryptophan to niacin in rats was investigated using the current methods for determination of the intermediate metabolites. Rats were fed with diets with or without B1 for 33 days. The body weight gain and food intake in the B1-free group were almost the same as the control group for 10 days, but, they steeply dropped after that time and the conversion ratio of tryptophan to niacin began to increase. The ratio reached 7-fold that of the control group on the last day of the experiment. This finding seriously differed from the previous reports, which described that B1 was needed in the first part of tryptophan conversion to niacin and that the conversion ratio of tryptophan to niacin decreased in B1-deficient rats. Furthermore, the activity of tryptophan oxygenase, in which it was reported that B1 is required for the tryptophan catalytic reaction, did not decrease but increased even when the B1-free diet was fed. These results suggest that there is a very small possibility of the direct involvement of B1 in the conversion of tryptophan to niacin.

Animals↗

[Negative potential auditory brainstem response with 3-msec latency in profoundly deaf patients: characteristics and relationship to vestibular evoked response].

A large negative deflection with a latency of 3 msec was observed in the auditory brainstem response (ABR) waveforms of 48 patients (6.5%), [59 ears (5.8%)] in 740 patients with profound peripheral deafness (1,009 ears) between 1978 and 1990 at our department. This negative deflection was termed the "N3 potential." We reviewed some of these patients and discuss some common characteristics found in abnormal ABR waveforms. We also inquired into the conditions and origins of these potentials. Although virtually all patients were less than 10 years of age, the N3 potential was also observed in the ABR waveform of adult patients. There were no sex differences. In the majority of patients audiograms showed no response to the maximum output of an andiometer in the high frequency range and a residual response in the low frequency range. The most common cause of deafness was "unknown" in children, and "sudden deafness" in adults. The N3 potentials were noted at intensities of 80 dBnHL or greater. A high repetition rate (83.3/sec) of the click stimulus influenced the latency and amplitude of the N3 potential. As the stimulus intensity increased, the amplitude of the potential increased, and the latency decreased. The potential was replicated on retesting within less than a month. The N3 potential had a consistent latency and amplitude over the scalp. We conclude that the N3 potential was a physiological "neural" response evoked by a loud sound rather than by an electrical artifact. The N3 potential was most likely not an auditory evoked response or a response from a semicircular canal, because of the 3-msec latency and sharpness of the waveform, with lack of vertigo. The results suggest that the N3 potential may be a saccular acoustic response.

Acoustic Stimulation↗

In vitro and in vivo evaluation of BO-2727 against imipenem- and/or meropenem-resistant Pseudomonas aeruginosa.

The in vitro and in vivo activity of BO-2727, a carbapenem antibiotic, against resistant clinical isolates of Pseudomonas aeruginosa was studied. The geometric mean MICs against three groups of clinical isolates resistant to imipenem, meropenem and both carbapenems were 4.28, 4.08 and 5.44 micrograms/ml, respectively. BO-2727 also inhibited multiply antibiotic resistant isolates and laboratory mutants including a nalB-type mutant, which showed resistance to antibiotics such as imipenem, meropenem, ceftazidime, and/or ciprofloxacin, at less than 1.56 micrograms/ml. Overall, BO-2727 was 4-fold more active than biapenem, meropenem, panipenem and imipenem with an MIC90 of less than 6.25 micrograms/ml. The presence of basic amino acids in minimal medium less affected the antipseudomonal activity to a minimal extent, suggesting that BO-2727 has diverse penetration routes through the outer membrane other than OprD channel, which facilitates the diffusion of basic amino acids and carbapenems. The in vitro activity of BO-2727 reflected well in its therapeutic efficacy in experimental systemic infection in mice. These results suggest a possibility for the development of antipseudomonal carbapenems having activity against imipenem- and/or meropenem-resistant P. aeruginosa as well as a broad spectrum encompassing Gram-positive and -negative bacteria.

Animals↗

UK-3A, a novel antifungal antibiotic from Streptomyces sp. 517-02: fermentation, isolation, structural elucidation and biological properties.

A novel antifungal antibiotic, UK-3A, was obtained from the mycelial cake of Streptomyces sp. 517-02. UK-3A was very similar in structure to UK-2A, a structural relative of antimycin A. The antifungal spectrum of UK-3A was relatively broad (MICs for yeasts and filamentous fungi: 1.56-6.25 and 0.39-1.56 micrograms/ml, respectively). The cytotoxic activity of UK-3A was weak (IC50: 18-100 micrograms/ml).

Antibiotics, Antineoplastic↗

[Clinical analysis of adjuvant chemotherapy using 5-fluorouracil, leucovorin and cis-diamminedichloroplatinum for patients with advanced and recurrent gastric cancer].

The chemotherapy combining 5-FU, CDDP, and LV was conducted in 17 patients with advanced and recurrent gastric cancer. The regimen consisted of 5-FU (by continual infusion 600 mg/m2/day for 5 days), CDDP (low-dose consecutive drip infusion, 2 hours 20 mg/m2/day for 3 days) and LV (by bolus infusion 20 mg/ m2/day for 5 days). Advanced gastric cancer was found in 12 cases (operation performed in 9 cases and 7 cases resectable) and recurrent in 5 cases. Macroscopic judgment of efficacy in 10 recurrent and inoperable cases revealed CR in 1 patient, PR in 5 patients, NL in 2, and PD in 2 patients. The overall response rate was 60.0%. There were 7 resectable cases, 4 PR patients, 1 MR and 2 NC patients. The overall response rate was 57.1%. Operations were done in 9 of 12 patients with advanced gastric cancer. The histological effects in 7 cases with resectable cases were as follows: 1 patient of grade 0, 2 patients of grade 1a, 3 patients of grade 1b, and 1 patient of grade 2. The main adverse reactions were gastrointestinal symptoms, but in 3 cases thrombocytopenia was found. This chemotherapy for advanced and recurrent gastric cancer shows excellent clinical efficacy.

Adenocarcinoma↗

New sandwich ELISA for human urinary N-acetyl-beta-D-glucosaminidase isoenzyme B as a useful clinical test.

We have developed a new ELISA for quantifying N-acetyl-beta-D-glucosaminidase (NAG) isoenzyme B in human urine after raising monoclonal antibodies against the isoenzyme from human placenta. Though the obtained antibodies reacted not only to isoenzyme B but also to A, we could detect isoenzyme B selectively by a two-step sandwich ELISA with a pair of selected antibodies at low pH in the first reaction. The detected limit was 0.5 microgram/L for a sample volume of 25 microL. Within-run CVs ranged from 2.5% to 5.4% and between-run CVs ranged from 6.2% to 9.1%. Recoveries of NAG isoenzyme B added to each of three urine samples ranged from 91% to 114%. The dilution curves of urine samples showed good linearity. The cross-reactivity of NAG isoenzyme A was practically negligible (2-3%). The mean value for NAG isoenzyme B in spot urines from healthy adults was 2.9 micrograms/g creatinine. This ELISA method is rapid and precise enough for routine determination of NAG isoenzyme B in human urine.

Acetylglucosaminidase↗

Persistent sciatic artery aneurysm with ruptured internal iliac artery aneurysm.

A case of aneurysm of persistent sciatic artery with ruptured aneurysm of the internal iliac artery is reported. A 62-year-old man was admitted to our hospital in emergency because of abdominal severe pain. Abdominal CT and angiography showed aneurysm of the infrarenal aortic aorta and left internal iliac artery and left persistent sciatic artery. The persistent sciatic artery aneurysm was coursed down the left thigh. Left superficial femoral artery was supplying blood to the popliteal artery as normal connection. Emergency operation was performed. The left internal iliac aneurysm was ruptured to a retroperitoneal space. The aneurysm was replaced by a Y-shaped dacron double velour graft from the infrarenal abdominal aorta to right common iliac and left external iliac arteries, which was followed by a ligation at the origin of left persistent sciatic aneurysm. The pulsation of the left lower extremity was good and additional bypass procedure to the popliteal artery was not performed. The post-operative course of the patient was excellent and post-operative angiography showed normal anatomy of the left lower extremity. Optimal management of ruptured abdominal aneurysm thus requires not only an emergency operation but detailed observation of preoperative CT and angiography in order to scrutinize the associated vascular anomalies.

Aneurysm↗

Successful endoscopic injection sclerotherapy with N-butyl-2-cyanoacrylate following the recurrence of bleeding soon after endoscopic ligation for ruptured duodenal varices.

Bleeding from duodenal varices in a 63-yr-old man with alcoholic cirrhosis of the liver was found at endoscopy, and ligation surgery was carried out. Ten months after the operation, bleeding from the duodenal varices occurred and was treated by endoscopic ligation. However, after performing this procedure, bleeding again occurred 1 week later. Hemostasis was finally achieved by endoscopic injection sclerotherapy with N-butyl-2-cyanoacrylate. For the 22 months since the injection, the patient has been free from further bleeding. These results suggest that endoscopic injection sclerotherapy with N-butyl-2-cyanoacrylate was effective in bringing about immediate cessation of the bleeding in duodenal varices and that long-term hemostasis can be expected.

Duodenoscopy↗

Bactericidal effect of ecabet sodium on clarithromycin- and metronidazole-resistant clinical isolates of Helicobacter pylori.

Ecabet sodium showed a bactericidal effect on Helicobacter pylori NCTC 11637 which is susceptible to antimicrobial agents (Antimicrob. Agents Chemother, 39: 1295-1299, 1995). In the present study, we investigated the bactericidal effect of ecabet sodium on clarithromycin- and metronidazole-resistant strains of clinical isolates of H. pylori under acidic conditions. In a buffer supplemented with urea at pH 3.0, ecabet sodium decreased the number of viable cells in both isolates. In the morphological study, ecabet sodium changed the isolates from the bacilliform to the horseshoe-shaped form and denatured the cytoplasm. Ecabet sodium also showed the bactericidal effect on both isolates in buffers at pH 4.0 and 5.0, and the bactericidal effect was dependent on pH, i.e., the lower the pH, the greater the effect. These results suggest that the susceptibility of H. pylori to antimicrobial agents does not affect the bactericidal effect of ecabet sodium on H. pylori.

Abietanes↗

Kinetic analysis of furosine and pentosidine in CAPD patients.

Advanced glycation end products (AGEs) have been noted in the peritoneal tissue of continuous ambulatory peritoneal dialysis (CAPD) patients, and this may cause an increase in membrane permeability. In vivo and in vitro kinetic analysis was carried out on furosine and pentosidine, early and late glycation products. Plasma furosine and pentosidine were measured by HPLC in patients with renal dysfunction with or without diabetes mellitus (DM) and dialysate pentosidine and furosine in CAPD patients. Only those dialysis patients without residual renal function were used in this study. Plasma furosine was remarkably high in DM, hemodialysis (HD), and CAPD patients. Plasma pentosidine appeared to depend on renal function and was not influenced by diabetic condition. Plasma pentosidine was significantly higher in CAPD than HD patients. A weak positive correlation was noted between dialysate and plasma furosine and pentosidine, indicating the main source of furosine and pentosidine in PD effluent to be plasma. Serial dialysate sampling showed furosine and pentosidine to increase linearly. Mean dialysate/plasma (D/P) of furosine and pentosidine were 0.043 and 0.012, respectively. Protein-bound product size and in situ formation of furosine in the peritoneal cavity would be the reason for these differences in D/P. In situ formation of early glycation products in the peritoneal cavity may be concluded to take place in CAPD patients, and high plasma pentosidine may lead to its accumulation in tissue, resulting, possibly, in pathological change.

Adult↗

[A case of paradoxical cerebral embolism with 'spectacular shrinking deficit'].

A 66-year-old woman was admitted to our hospital because of abrupt onset of left hemiparesis and confusional state. Ten hours prior to admission, she developed difficulty in left hand movement, and her family noticed cloudiness of consciousness and gait disturbance. Neurological examination revealed only a hollow hand sign of the left hand without other neurological deficits. Cranial CT showed a low density area in the right superior parietal region, and the follow up CT on 6th hospital day exhibited contrast enhancement and hemorrhagic transformation in this area. Cerebral angiography demonstrated capillary blush and early venous filling in the right posterior parietal region. Transesophageal color-coded Doppler echocardiography (TEE-CD) showed a shunt flow via patent foramen ovale (PFO). Thus, we diagnosed this case as paradoxical cerebral embolism through PFO, which is characterized by rapid recovery of clinical manifestation, so-called spectacular shrinking deficit. Even in elderly patients with embolic stroke of unknown origin, TEE-CD should be performed to investigate PFO.

Aged↗

Refractory anaemia with ringed sideroblasts concurrent with multiple myeloma--a brief review of the recent literature.

The report describes a patient in whom myelodysplastic syndrome and multiple myeloma (MM) were simultaneously present. This patient manifested an IgA-lambda type of MM concurrent with a refractory anaemia with ringed sideroblasts (RARS) without prior therapy. His bicytopenia could not be improved by vitamin B6 regardless of a reduced serum vitamin B6 concentration. A review of the literature suggests that myelodysplastic syndrome (MDS), chronic neutrophilic leukaemia (CNL) and idiopathic myelofibrosis (IMF) are the most frequent disorders associated with MM. The IgA type seems to be associated more commonly with these disorders. The mechanisms responsible for the development of plasma cell proliferation are diverse; the neoplastic transformation of a common progenitor, the involvement of the lymphoplasmacytic system and/or chronic reticuloendothelial stimulation may play a role in the occurrence of such hybrid haematological disorders.

Aged↗

[Efficacy of combination chemotherapy with mitoxantrone, vincristine, doxifluridine and prednisolone for recurrence of breast cancer].

We treated fifteen patients with recurrent breast cancer by a combination of mitoxantrone (8 mg/m i.v., day 1), vincristine (1.2 mg/m i.v., day 1), doxifluridine (800 mg/body po, everyday) and prednisolone (30 mg/body po, day 1-7). Cycles were repeated every 3 weeks and all patients received more than 2 cycles. A response to treatment was observed in 9 of 15 evaluable patients (60.0%) with 4 complete remissions and 5 partial remissions. Eight patients were previously exposed to anthracyclines. In 5 of 7 cases with no previous chemotherapy, treatment was effective, and in 4 of 8 cases previous chemotherapy was effective. The toxicity was primarily leucopenia (86.7%), and 9 patients received G-CSF therapy. Other toxicities (alopecia, neurologic and general fatigue) were mild. Two patients with heart failure were recognized and treated with other therapy. This chemotherapy is effective for the treatment of recurrent breast cancer.

Administration, Oral↗

High-efficiency full-length cDNA cloning by biotinylated CAP trapper.

We have devised a method for efficiently constructing high-content full-length cDNA libraries based on chemical introduction of a biotin group into the diol residue of the cap structure of eukaryotic mRNA, followed by RNase I treatment to select full-length cDNA. The selection occurs by trapping the biotin residue at the cap sites using streptavidin-coated magnetic beads, thus eliminating incompletely synthesized cDNAs. When this method was used to construct a mouse brain full-length cDNA library, our evaluation showed that more than 95% of the total clones were of full length, and recombinant clones could be produced with high efficiency (1.2 x 10(7)/10 micrograms starting mRNA). The analysis of 120 randomly picked clones indicates an unbiased representation of the starting mRNA population.

Animals↗

Ca2+ entry induced by calcium influx factor and its regulation by protein kinase C in rabbit neutrophils.

Extracellular application of acid extract from platelet-activating factor- or thapsigargin-treated rabbit neutrophils induced a rise of cytosolic free calcium concentration ([Ca2+]i) in neutrophils and adrenal chromaffin cells suspended in Ca(2+)-containing, but not in Ca(2+)-deficient, medium. The ability of the extract to selectively induce Ca2+ entry was also confirmed by the increase in 45Ca2+ uptake and failure to stimulate Ca2+ release in digitonin-permeabilized neutrophils. 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited the extract-induced [Ca2+]i rise in a staurosporine (ST)-sensitive fashion, neither of which had any effect on its production. SK&F 96365 and econazole also reduced extract-induced Ca2+ entry. These results suggest that a Ca2+ entry-inducible substrate (calcium influx factor) is extracted from Ca2+ store-depleted neutrophils, and that its action may be regulated by protein kinase C and certain pharmacological agents.

Adrenal Glands↗

Cytogenotoxicities of sublimed urethane gas to the mouse embryo.

Urethane (ethyl carbamate) which has long been used for commonly used drugs and has proven to be useful in the formation of products in every-day use, is volatile, and small amounts sublime spontaneously. Pregnant ICR mice were maintained in the vinyl chamber (45 liter) which was ventilated 4 times per hour. To inhale urethane gas, air was passed first through a glass bottle containing 500 g of crystalline urethane and then into the vinyl chamber. Concentration of the sublimed urethane gas in the chamber was 1.28 +/- 0.08 mg/l, and sublimed urethane gas produced significantly high incidence of chromosomal aberrations in the cells of whole embryo, when mice inhaled it for 48 h from day 9 to day 11 of pregnancy. High and significant incidence of chromosomal aberrations (36.0%) was detected in the embryo 3 h after urethane gas inhalation, but decreased to 5.3% at 24 h after exposure and showed no significant differences from controls after 48 h, while the incidence in bone marrow cells from the adult (pregnant) mice was lower (21.5%) at 3 h after exposure but a significant increase remained until 72 h after exposure. A majority of chromosomal aberrations was chromatid types. As a consequence of cellular damages by urethane gas inhalation during pregnancy, significantly high incidence of fetal deaths and congenital malformations (cleft palate, polydactyly, tail anomaly etc.) was induced in the offspring. Thus, we must be aware of the risk of volatile chemicals, because it is difficult to perceive and avoid hazardous exposure via respiration.

Abnormalities, Drug-Induced↗

Flow cytometry analysis of alpha1-adrenoceptor subtypes.

To characterize the alpha1-adrenoceptor subtypes, we developed a flow cytometry method using the fluorescent ligand BODIPY-FL prazosin and the anti-peptide antibody against the alpha1b-adrenoceptor amino terminus (designated 1B-N1-C) as probes. Three alpha1-adrenoceptors (alpha1a, alpha1b and alpha1d) expressed in CHO cells were detected by BODIPY-FL prazosin; however, only alpha1b-adrenoceptor subtype was detected by the anti-peptide antibody 1B-N1-C. Furthermore, the flow cytometry analysis with 1B-N1-C specifically identified alpha1b-adrenoceptor in native cells of hamster DDT1-MF2 cells, rat hepatocytes and cardiomyocytes.

Amino Acid Sequence↗