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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 1,027 records · Page 57Linked to original sources

Capuramycin, a new nucleoside antibiotic. Taxonomy, fermentation, isolation and characterization.

A new antibiotic capuramycin was isolated from the culture filtrate of Streptomyces griseus 446-S3 by adsorption and partition column chromatography. Based on its chemical structure being an uracil nucleoside with a caprolactam substituent, this substance was named as capuramycin. This paper describes the taxonomy of a producing organism, fermentation, isolation, characterization and biological properties of capuramycin.

Aminoglycosides↗

Inhibition of experimental pulmonary metastasis of mouse colon adenocarcinoma 26 sublines by a sialic acid:nucleoside conjugate having sialyltransferase inhibiting activity.

The total and sialidase-releasable sialic acid contents of murine colon adenocarcinoma 26 sublines of high (NL-17) and low (NL-44) metastatic potential were found to be positively correlated with their ability to undergo metastasis. Furthermore, sialyltransferase activity of intact NL-17 cells was higher than that of NL-44 cells. These findings suggest that sialic acid on the cell surface may play a role in the metastasis of these cells. Therefore, the effect of a sialyltransferase inhibitor, 5-fluoro-2',3'-isopropylidene-5'-O-(4-N-acetyl-2,4-dideoxy-3,6,7,8-tetra -O -acetyl-1-methoxycarbonyl-D-glycero-alpha-D-galactooctapyranosyl)u ridine (Kl-8110), on the experimental lung metastasis of NL-17 or NL-44 cells was examined. Kl-8110 inhibited the transfer of sialic acid to its endogenous acceptor in NL-17 and NL-44 cells. NL-17 or NL-44 cells were injected into the tail veins of mice, and the metastasis-inhibiting activity of Kl-8110 was evaluated on the basis of both the lung weight and the number of pulmonary surface nodules about 3 wk after the tumor cell injection and of the survival ratio of mice inoculated with the tumor cells. Pretreatment of tumor cells with Kl-8110 together with i.v. injection of Kl-8110 caused significant inhibition of pulmonary metastasis of both NL-17 and NL-44 cells. Inhibition of metastasis and prolongation of survival were also observed on i.v. injection of Kl-8110 without pretreatment of the tumor cells with Kl-8110, but the degree of inhibition was lower than that in the case of the two treatments together. Kl-8110 itself had neither cytostatic nor cytotoxic effects on NL-17 and NL-44 but reduced the retention of tumor cells in the lungs. This antimetastatic effect of Kl-8110 may be due to modification of the tumor cell surface resulting from inhibition of sialyltransferase by Kl-8110. In addition, a beta-linked sialic acid:nucleoside conjugate (Kl-8111) and an equimolar mixture of Kl-8110 and Kl-8111 (Kl-414) also inhibited the metastatic ability of NL cells to the same extent as Kl-8110 did.

Adenocarcinoma↗

Nanosecond fluorescence studies of noncovalent interaction of monomeric and dimeric intercalators with DNA.

The noncovalent interaction of 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) and its derivatives, which are potent mutagens isolated from L-glutamic acid pyrolysate, with calf thymus DNA was studied by steady-state and nanosecond fluorescence spectroscopies. The fluorescence of these compounds exhibits static quenching by noncovalent interaction with DNA. Fluorescence lifetimes of the free and intercalated states of these compounds were determined to be 9-10 and 0.5-1 ns, respectively. The bisintercalative effect of the dimeric analogue of Glu-P-2, bis(Glu-P-2)spermine (2GP-SP), to DNA was also investigated. This 2GP-SP, which has two Glu-P-2 moieties at each end of spermine, indicates a strong intramolecular interaction exhibiting remarkable quenching of fluorescence spectrum and lifetime (tau = 3.5 ns) in the absence of DNA. In the presence of DNA, however, the 3.5-ns lifetime component of fluorescence disappeared, and a two-exponential decay of fluorescence (t = approximately 10 and 1.5 ns) was observed at a DNA concentration of more than approximately 0.001 mM P, while the solution containing a very dilute DNA concentration (less than or equal to 0.001 mM P) exhibits a three-component decay of fluorescence (1.5, 3.5, and approximately 10 ns). The potent bis intercalation of two moieties in 2GP-SP with an identical DNA molecule was suggested by the DNA-concentration dependence of these fluorescence lifetimes and their intensity.

Animals↗

Experimental studies on myocardial glucose metabolism of rats with 18F-2-fluoro-2-deoxy-D-glucose.

The myocardial uptake of 18F-FDG was investigated under various conditions, and compared with brain and tumor uptake as a function of blood glucose level. The uptake by the heart of normal feeding rats was rapid and remained essentially unchanged up to 2 h after 18F-FDG injection, approximately 3%-4% dose/g tissue. On the other hand, the myocardial uptake of fasted rats was significantly lower than that of control rats throughout the course of the study, and it was about 0.3%-0.4% dose/g tissue. Myocardial uptake of 18F-FDG was relatively constant at glucose levels under about 120 mg/100 ml and increased steeply at higher blood glucose levels. In contrast, brain uptake decreased linearly with increasing levels of blood glucose, revealing a strong negative correlation between brain uptake of 18F-FDG and blood glucose levels. The tumor uptake pattern remained relatively unchanged, irrespective of blood glucose levels. It was revealed that the glucose demands of brain, heart, and tumor were entirely different. After a glucose load, the myocardial uptake of fasted rats increased only slightly from 0.4% to 0.6% dose/g tissue, in spite of transitional hyperglycemia. In contrast, insulin caused myocardial uptake to increase extraordinarily, although it caused a decrease in blood glucose levels.

Animals↗

Airflow, volume, and durational characteristics of oral reading by the hearing-impaired.

This study examined airflow, volume,and durational characteristics of speech produced by hearing-impaired subjects using a face-mask-pneumotachometer-pressure-transducer system. Results or oral reading of a standard passage indicated that, in comparison to the normal-hearing subjects, the speech respiration of the hearing-impaired was characterized by high air consumption manifested as high air expenditure per syllable, high average expiratory airflow rates, and high peak-airflow rates; frequent inspirations; inspirations at linguistically inappropriate places; short duration of expiration; and large individual differences. These characteristics were especially prominent among the more severely hearing-impaired individuals. Correlational analysis revealed that more frequent inspirations were associated with poorer overall speech proficiency while high air consumption was closely related to a breathy voice quality.

Adolescent↗

Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions in the rat.

This study was designed to determine whether oxygen-derived free radicals play a role in the pathogenesis of gastric lesions produced by hypotensive ischemia in the rat. To achieve this goal, allopurinol, an inhibitor of xanthine oxidase (the enzyme responsible for the formation of superoxide radicals); superoxide dismutase, a scavenger of superoxide radicals (O2-); and dimethyl sulfoxide, a scavenger of hydroxyl radicals (OH) were used. In the anesthetized rat, HCl (0.1 N) was instilled into the pylorus-ligated stomach, and the rat was bled to reduce the blood pressure to less than 30 mmHg. The blood pressure was maintained at less than 30 mmHg for 20 min and then the shed blood was retransfused. Twenty minutes after the retransfusion the rat was killed, the stomach was removed, and the area of gastric mucosal lesions was measured. Both allopurinol and superoxide dismutase, but not dimethyl sulfoxide, significantly protected against hemorrhagic shock-induced gastric lesions. These findings suggest that oxygen-derived free radicals, particularly O2-, play an important role in the formation of gastric lesions produced by ischemia plus HCl.

Allopurinol↗

Role of blood flow in gastric and duodenal mucosal injury in the rat.

The hemorrhagic hypotension model in anesthetized rats was used to study the relationship between gastric and duodenal mucosal blood flow and susceptibility to acid-induced injury. Mucosal blood flows measured by the hydrogen gas clearance technique in the corpus, antrum, and duodenum all showed a significant linear correlation with mean blood pressure, decreasing progressively as blood pressure fell. Significant gastric mucosal lesions occurred only after mean blood pressure and hence, mucosal blood flow was reduced to below 40% of baseline values. In contrast, duodenal mucosal lesion formation was related in a linear manner to decrease in mean blood pressure or blood flow. We conclude that mild reductions in blood flow are more important in the duodenum than in the stomach in increasing susceptibility of the mucosa to acid-induced injury.

Animals↗

Gigantism associated with McCune-Albright's syndrome.

The case of a 16 year-old boy with McCune-Albright's syndrome which is rarely accompanied by gigantism was studied endocrinologically. The stimulation of growth hormone (GH) release by hypoglycemia, the decline of elevated GH by hyperglycemia and a little lower somatostatin like immunoreactivity (SLI) may support abnormalities of hypothalamic function, but the existence of pituitary microadenoma cannot be ruled out because of the paradoxical suppression of GH release by oral administration of bromocriptine (CB-154) and L-DOPA and the stimulation of GH release by intravenous administration of TRH.

Adolescent↗

Sensitive radioimmuno assay for 2',5'-oligoadenylates using a novel 125I-labeled derivative of 2',5'-triadenylate 5'-triphosphate.

A novel 125I-labeled derivative of 2',5'-triadenylate 5'-triphosphate, pppA2'p5'A2'p5'A, with high specific radioactivity was synthesized by coupling of periodate-oxidized pA2'p5'A2'p5'A with beta-alanyltyrosine methyl ester followed by 5'-triphosphorylation and iodination with 125I. Antisera toward 2',5'-oligoadenylate 5'-triphosphate were produced in rabbits by immunization with the conjugate of pppA2'p5'A2'p5'A2'p5'A with bovine serum albumin, and an antiserum with high specificity and high sensitivity for 2',5'-oligoadenylates was selected and tested extensively. Radioimmuno assaying of 2',5'-oligoadenylates was carried out by a competitive double antibody method in which the amount of the antibody bound to the 125I-labeled probe was measured after precipitation with goat anti-rabbit IgG. The concentration of pppA2'p5'A2'p5'A required for 50% inhibition of the binding between the antiserum and the probe was 0.6 nM. The cross reactivity of the antiserum with the 3',5'-triadenylate was more than 10,000 times weaker compared to in the case of 2',5'-oligoadenylates. Very low or no cross reaction was observed with ATP, AMP, and adenosine. The radioimmuno assay using the 125I-labeled compound and the antiserum allows the direct analysis of 2',5'-oligoadenylates in the range of 4 fmol to 1 pmol (0.04-10 nM in a 100 microliter sample). This assay was applied to the measurement of the activity of 2',5'-oligoadenylate synthetase in cells stimulated by interferon. The properties of the 125I-labeled derivative of pppA2'p5'A2'p5'A are described.

2',5'-Oligoadenylate Synthetase↗

Right-sided infective endocarditis combined with mitral involvement in a patient with ventricular septal defect.

An autopsy case of right-sided infective endocarditis combined with mitral valvular involvement in a 20-year-old male Japanese with ventricular septal defect (VSD) was reported. The vegetations were found on the endocardium bordering VSD, tricuspid valve, mural endocardium of the right ventricular outflow tract, and even the pulmonic valve, resulting in forming infective aneurysm of the pulmonary trunk. Streptococcus was morphologically identified in the vegetations obtained at autopsy. On the other hand, smaller vegetations were also noted on the mitral valve. The mechanisms of the mitral extending were discussed when right-sided infective endocarditis associated with VSD preceded that on the mitral valve. The authors think that mitral regurgitation in relation to VSD and right to left shunt through VSD which occur even temporarily may be the most important mechanism responsible for the mitral valvular involvement. Several differences between right-sided and left-sided infective endocarditis were also reviewed.

Adult↗

Domains involved in osmoregulation of the ompF gene in Escherichia coli.

Expression of the ompF gene, which is under the control of the OmpR protein, is regulated by the osmolarity of the medium. To study the mechanism of osmoregulation, plasmids carrying two different types of chimeric genes were constructed. In one type, the coding region of the ompF gene was linked to the trp promoter (trpPO) preceding ompF, and in the other type the ompF upstream region, mostly composed of the region for regulation by OmpR and the promoter region, was linked to the lacZ gene by protein fusion. Expression of beta-galactosidase by the lacZ chimeric gene was OmpR dependent and osmoregulated as sensitively as that of the intact ompF gene. In the ompR20 background the direction of osmoregulation was opposite that of normal osmoregulation, as was the direction of osmoregulation of the intact ompF gene. Osmoregulation was also observed with trpPO-ompF chimeric genes. However, the regulation was not as sensitive to the osmolarity of the medium as was regulation of the intact ompF gene and was independent of OmpR. These results suggest that OmpR-dependent osmoregulation played a primary role in the osmoregulation of ompF expression and that ompR-independent osmoregulation most likely did not play a crucial role. Studies with a series of trpPO-ompF chimeric genes also suggest that the untranslated leader region, about 100 base pairs in length, between the transcription initiation site and the initiation codon was not required for osmoregulation.

Bacterial Outer Membrane Proteins↗

pH change in artificial dental plaque formed by glucosyltransferase and some oral bacteria during batch and continuous culture.

Streptococcus mutans alone or cell-free glucosyltransferase (G-Tase)-together with either Streptococcus sanguis, Streptococcus salivarius, Actinomyces viscosus, or Lactobacillus casei cells-formed artificial dental plaque that firmly adhered to glass electrodes in a continuous culture system containing sucrose. The pH in these artificial plaque samples decreased more than did that of the surrounding medium. In the absence of GTase, the bacteria other than S. mutans did not form firmly-adhering plaque on glass electrodes. The pH of the plaque formed with GTase alone did not show the pH decrease seen when the plaque contained bacteria, but, because it catalyzed the synthesis of glucan, it is suggested that the glucan acts as a diffusion barrier to retard acid loss from plaque containing acid-producing bacteria.

Actinomyces↗