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Biomedical subjects

R Ohta

Publications and source records attributed to R Ohta.

At least 37 records · Page 2Linked to original sources
PubMed1999

Antimicrobial activity of the thiosulfinates isolated from oil-macerated garlic extract.

Three thiosulfinates were isolated from oil-macerated garlic extract, and their structures were identified as 2-propene-1-sulfinothioic acid S-(Z,E)-1-propenyl ester [AllS(O)SPn-(Z,E)], 2-propenesulfinothioic acid S-methyl ester [AllS(O)SMe], and methanesulfinothioic acid S-(Z,E)-1-propenyl ester [MeS(O)SPn-(Z,E)]. This is the first report of isolating these thiosulfinates from oil-macerated garlic extract. Antimicrobial activities of AllS(O)SPn-(Z,E) and AllS(O)SMe against Gram-positive and negative bacteria and yeasts were compared with 2-propene-1-sulfinothioic acid S-2-propenyl ester [AllS(O)SAll, allicin] which is well-known as the major thiosulfinate in garlic. Antimicrobial activity of AllS(O)SMe and AllS(O)SPn-(Z,E) were comparable and inferior to that of allicin, respectively. This result suggested that the antimicrobial activity of 2-propene sulfinothioic acid S-alk(en)yl esters were affected by alk(en)yl groups. The order for antimicrobial activity was: allyl > or = methyl > propenyl.

Anti-Bacterial Agents↗
PubMed1999

Structural and functional analysis of the control region of the human DNA topoisomerase II alpha gene in drug-resistant cells.

We have previously shown that the DNA topoisomerase II alpha (topo II alpha) gene is down-regulated in VP16/VM26-resistant cells at the transcriptional level. To determine the DNA elements responsible for down-regulation, the transcriptional activities of luciferase reporter constructs containing various lengths of the promoter sequences were investigated by transient transfection of two resistant cell lines, KB/VP2 and KB/VM4. The transcriptional activities of the full-length promoter (-295 to +85) and of three deletion constructs (-197, -154 and -74 to +85) were significantly down-regulated in resistant cells. In contrast, the transcriptional activity of the minimal promoter (-20 to +85) in resistant cells was similar to that in parental KB cells. Furthermore, introduction of a mutation in ICE1 abolished the down-regulation of the topo II alpha promoter activity in drug-resistant cells. In vivo footprinting analysis of topo II alpha gene promoter revealed several specific protein-binding sites, a GC box, ICE1, ICE2 and ICE3. In vivo footprinting analysis also identified a cluster of hypersensitive sites. However, there was no marked difference in protein-binding sites between parental and resistant cells. To confirm our previous results, we have established the VP16-resistant cell lines T12-VP1 and T12-VP2 from T12 cells derived from human bladder cancer T24 cells stably transfected with the chloramphenicol acetyltransferase reporter gene driven by the topo II alpha gene promoter. The expression to topo II alpha was down-regulated in both cell lines. We also found that CAT gene expression was significantly decreased to one-fifth of that in T12 parental cells. These results suggest that the expression of the topo II alpha gene requires the binding of multiple factors to the core promoter and is down-regulated at the transcriptional level, probably through binding of a negative factor to ICE1 in drug-resistant cells.

Antigens, Neoplasm↗
PubMed1998

Comparative study of behavioral development between high and low shuttlebox avoidance rats.

Previously, we reported that high- and low-avoidance animals (HAA and LAA, respectively), selectively bred for different avoidance response rates in a shuttlebox avoidance test, showed additional behavioral differences in wheel cage activity and in water maze performance after weaning. In the present study, physical and behavioral development were examined in HAA and LAA during the preweaning period. As compared to HAA, LAA offspring showed lower body weight, delayed eye opening, poorer performance in pivoting and negative geotaxis, and increased open-field activity. A fostering study indicated that these differences observed in eye opening, pivoting, negative geotaxis, open-field activity, swimming speed, shuttlebox avoidance and wheel cage activity were independent of maternal care. Only the pup weight was strongly dependent on the maternal line. These results indicate that behavioral differences between HAA and LAA observed in the pre- and postweaning periods may be linked to the avoidance genotype, but the difference in pup weight may be caused by maternal care.

Animals↗
PubMed1997

High-performance liquid chromatographic determination of seratrodast and its metabolites in human serum and urine.

A high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of seratrodast, a new antiasthmatic drug, and its metabolites (M-I to M-III) in human serum and urine. The method for serum and urine with and without enzymatic hydrolysis using beta-glucuronidase involved liquid-liquid extraction and chemical oxidation with iron(III) chloride. The compounds in the extract were analyzed using HPLC with UV detection at 266 nm. The detection limits of seratrodast, M-I, M-II and M-III in serum and urine were 5-10 and 5-20 ng/ml, respectively, and those of deconjugated compounds in urine were 10-50 ng/ml. The method was applicable for human serum and urine from clinical trials.

Anti-Asthmatic Agents↗
PubMed1997

Traumatic pancreatic duct rupture in a child diagnosed by endoscopic retrograde pancreatography.

We report on a child who sustained blunt abdominal trauma with pancreatic duct rupture diagnosed by preoperative endoscopic retrograde pancreatography (ERP). Duct laceration remained undiagnosed by computerized tomography or ultrasonography. Preoperative ERP is the only known method for the accurate diagnosis of injury to main pancreatic duct. Even in children with pancreatic trauma we recommend ERP before any surgery is attempted to help in decisions on operative strategy.

Abdominal Injuries↗
PubMed1993

Effects of water content on physical and chemical stability of tablets containing an anticancer drug TAT-59.

(E)-4-[1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-(4-isopropyl) phenyl]-1-butenyl]phenyl monophosphate (TAT-59) is a new drug for the treatment of breast cancer. Physical and chemical stability of a tablet consisting of TAT-59 powder and a few excipients (Formulated tablet), a tablet consisting of only TAT-59 powder (TAT-59 tablet) and TAT-59 powder itself was evaluated based on water content, tensile strength, porosity, the amount of TAT-59 and its hydrolysis product, DP-TAT-59. The water content of Formulated tablet increased with relative humidity (RH), whereas that of TAT-59 tablet and TAT-59 powder scarcely changed. The equilibrium water content of Formulated tablet was much greater than that of the TAT-59 tablet or TAT-59 powder due to adsorbed moisture by the excipients. The tensile strength and porosity of Formulated tablet decreased and increased linearly, respectively, with increasing water content. The degradation rate of TAT-59 decreased in the following order: Formulated tablet > TAT-59 tablet > TAT-59 powder. The relationship between equilibrium water content and degradation rate of the Formulated tablet was determined by the Carstensen equation, in which the interaction order between the drug and water content was 1.9, and the degradation of TAT-59 in Formulated tablet was related to water content. Thus, it was found that the degradation of TAT-59 was accelerated by compression and addition of excipients.

Antineoplastic Agents↗
PubMed1990

Normative data and the effect of correction for prematurity on test scores in the psychomotor development of extremely low birthweight infants.

This study was concerned with the problem how we should allow for gestational age at birth when evaluating psychomotor development in extremely low birthweight (ELBW) infants. The consequences of the use of corrected and uncorrected developmental test scores as to the degree of prematurity were studied in 27 consecutive ELBW children who had been categorized as being normal on neurological and psychological testing at 5 1/2 years. The present study provides evidence that the overall trend of psychomotor development in normal ELBW children is not accelerated, but is guided by maturation of the central nervous system. This study also suggests that there are no significant differences in the predictive value of corrected and uncorrected DQ scores after 2 years of age with respect to IQ scores at 5 1/2 years.

Aging↗
PubMed1990

[Effects of lung volume levels and trapidil on transdiaphragmatic pressure in young healthy subjects].

Effects of lung volume levels, and effect of intravenous administration of Trapidil on the maximal force developed by the diaphragm were investigated by the measurement of transdiaphragmatic pressure (Pdi) in 10 healthy young subjects. To evaluate transdiaphragmatic pressure, delta Pdimax was used. delta Pdimax was calculated by the subtraction of the transdiaphragmatic pressure at FRC (Pdi FRC) from the maximal transdiaphragmatic pressure (Pdimax) at each lung-volume level. Regardless of the administration of Trapidil, delta Pdimax was highest at FRC in each subject. When Trapidil was administered, Pdimax increased in cases where absolute Pdimax FRC was initially low. The relation between changes of delta Pdimax at FRC after Trapidil administration and delta Pdimax showed significant linear correlation (r = -0.85, p less than 0.002). These results suggest that FRC is the most adequate lung volume level to produce an effective transdiaphragmatic pressure, and that Trapidil increases the muscle force of the diaphragm in cases where the force is initially low in young healthy subjects.

Adult↗
PubMed1988

Consistency and changes in the development of extremely low birthweight infants.

Thirty infants who weighed less than 1,000 g were evaluated as to neurological functioning and mental ability at 1 year and, again, at 3 years of age. The results of the examinations showed the high correlation in the neurological status between infancy and the preschool period, particularly, for children who were diagnosed as being clearly normal or abnormal at 1 year. There was a high percentage of psychomotor delays in those with ophthalmic complications.

Cerebral Palsy↗
PubMed1979

Self-mutilation and sleep stage in the Lesch-Nyhan syndrome.

Correlation of self-mutilation and sleep stage in the Lesch-Nyhan syndrome was studied by a polygraphic method. Five patients and three control boys were monitored with EEG, EOG, EMG, ECG and respiration throughout the night. The results were as follows: 1. The sleep-time of the patients was much disturbed during the night. 2. Decreased REM density was noticed with low DQ of the patients. 3. Self-mutilation during sleep-time was observed a lot in stages 1, 2, and REM in two cases. 4. No correlation was observed between body movement and self-mutilation in the Lesch-Nyhan syndrome. These data suggested functional disorders of the frontal lobe in the patients.

Adolescent↗
PubMedDate not supplied

Effect of butyl benzyl phthalate in Sprague-Dawley rats after gavage administration: a two-generation reproductive study.

Butyl benzyl phthalate (BBP), a plasticizer, has been shown in in vitro studies to be weakly estrogenic, and in in vivo studies to possess testicular toxicity and teratogenicity, but few experimental data on BBP multigeneration effects on reproduction in mammals are available. The present two-generation reproductive study was conducted in male and female Sprague-Dawley rats using oral doses of 0, 20, 100, and 500 mg/kg/day BBP. Endpoints were chosen in order to evaluate both subchronic and reproductive toxicity. In the parent animals (F(0)), a decrease in body weight gain was observed in males in the 500 mg/kg/day group, although no significant decrease in food consumption was found. No dose-related changes were observed in estrous cyclicity, fertility, or lactation. A dose-dependent increase in kidney weight in rats of both sexes, an increase in liver weight in males, and a decrease in the weight of the ovaries in females were observed. No macroscopic or microscopic changes were found in the reproductive system of males or females. Oral administration of BBP caused a decrease in the serum concentration of testosterone, and an increase in FSH. In the next generation (F(1)), the body weight of male and female offspring at birth in the 100 and 500 mg/kg groups was significantly decreased, and the body weight in the 500 mg/kg group was lower throughout the study, while viability was not affected. Anogenital distance (AGD) at birth was decreased in male pups and was increased in female pups of the 500 mg/kg/day group. Preputial separation for male offspring in the 500 mg/kg/day group was delayed, while vaginal opening for female offspring in this group was not affected. BBP did not affect reproductive ability, including delivery and lactation, at any dose whereas macroscopic and microscopic changes of the testis, and decreased serum concentrations of testosterone were observed in male offspring of the 500 mg/kg/day group after puberty. From these data, it would appear that 20 mg/kg BBP is a no observed adverse effect level (NOAEL) for reproductive effects on parent animals and the next generation.

Administration, Oral↗
PubMedDate not supplied

Behavioral characteristics of micrencephalic rats in high and low shuttlebox avoidance lines.

Rats of two lines, selectively bred for high and low shuttlebox avoidance response, and unselected line of the Sprague-Dawley (SD) rats were given an IP injection of methylnitrosourea (MNU) at 5 mg/kg on day 13 of gestation. Their offspring, all with micrencephaly, were subjected to the Biel maze, shuttlebox avoidance, and wheel cage activity tests during 6 to 9 weeks of age. Results from micrencephalic rats were compared with those obtained from untreated control offspring of the respective lines. The MNU-treated offspring in each line made more errors than controls in the Biel maze, and showed similar avoidance responses to controls in the shuttlebox test. Line differences in effects of MNU treatment were observed in elapsed time in the straight channel, extinction of shuttlebox avoidance responses, and activity in the wheel cage. These line differences in effects of MNU treatment may be related to control baseline levels of behavior in which the three lines differed widely, and suggest that the behavioral effects of prenatal MNU treatment vary in rats depending on the lines used.

Animals↗
PubMedDate not supplied

Postnatal behavior in hatano high- and low-avoidance rats following prenatal exposure to low-dose methylazoxymethanol.

The hypothesis that genetic factors influence behavioral effects was tested in rats exposed prenatally to methylazoxymethanol (MAM). We examined whether baseline behavior is an important factor influencing behavioral effects, and whether a behaviorally selected strain was useful for study of neurobehavioral teratology. Pregnant high- and low-avoidance animals (HAAs and LAAs) of the Hatano strain, selectively bred for high and low shuttlebox avoidance responses, respectively, were given an IP injection of a low dose of MAM (15 mg/kg) on day 14 of gestation. The offspring of these animals were subjected to behavioral tests for locomotor activity (running-wheel and open-field tests) and learning ability (Biel maze and shuttlebox avoidance tests). There were no significant effects of MAM on running-wheel activity or shuttlebox avoidance learning, whereas the number of errors in the Biel maze was increased in the MAM offspring of both strains. Interestingly, open-field activity of the MAM offspring was markedly decreased in LAAs but not in HAAs. Therefore, an additional experiment was performed to determine plasma levels of ACTH and corticosterone following open-field exposure. When compared to control offspring of the respective strains, plasma levels of ACTH and corticosterone were not altered by prenatal MAM treatment in LAAs. Instead, the MAM offspring in HAAs exhibited decreased ACTH levels in absence of behavioral alterations. These results demonstrated that prenatal exposure to low doses of MAM may alter postnatal behavior and endocrine response of the offspring, although to a differing degree in HAAs and LAAs. Our observations suggested that behaviorally selected strains are sensitive to neurobehavioral teratogens such as MAM.

Adrenal Glands↗
PubMedDate not supplied

Living-related auxiliary partial orthotopic liver transplantation for primary sclerosing chonangitis--subsequent removal of the native liver.

In Japan, living-related auxiliary partial orthotopic liver transplantation (APOLT) is mainly indicated for small-for-size grafts. We present the case of a 24 year-old patient with primary sclerosing cholangitis (PSC) who underwent a living-related auxiliary partial orthotopic liver transplantation for a small-for-size graft, that was subsequently excised. During the transplantation procedure, the native liver was freed from the surrounding tissues, and was only connected to the body by the right hepatic artery and right hepatic vein. The auxiliary extended left lobe graft, corresponding to 22% of the estimated recipient liver volume, was orthotopically transplanted after extended left lobectomy of the recipient native liver. Post-transplant CT-volumetry showed rapid increase of the graft volume with atrophy of the native liver, and GSA scintigraphy showed dominant function of the graft. Although hyper-bilirubinemia was prolonged by the removal of the native liver on the 18th post-transplantation day, it gradually subsided after plasmapheresis was performed twice, and the patient was discharged on the 77th post-transplantation day. We conclude, based on this case, that subsequent removal of the native liver is necessary in APOLT for patients with potential hepatic malignancies. The optimal timing of the removal of the remnant native liver should be determined based on CT-volumetry, GSA scintigraphy, and the liver biopsy specimen of the graft.

Adult↗
PubMedDate not supplied

Serum levels of interleukin-12 in patients with gastrointestinal cancer.

Interleukin 12(IL-12) is a heterodimeric cytokine that has potent anti-tumor and anti-metastatic activities. Although clinical trials of recombinant human IL-12 have begun in patients with several advanced malignancies, very few studies have investigated the preoperative serum levels of IL-12 in patients with gastric or colorectal cancer. The purpose of the present study was to investigate the relationships between the preoperative serum levels of IL-12 and clinicopathological factors in patients with gastric or colorectal cancer. Blood was obtained before surgery from 14 patients with gastric cancer and 15 patients with colorectal cancer. Serum levels of IL-12 was assessed using the quantitative sandwich enzyme immunoassay technique. Although not statistically significantly, low serum levels of IL-12 tended to be associated with gastric cancer patients who were node-positive, CEA positive, had tumors that penetrated the serosa, had tumors greater than 5 cm in diameter, were more than 60 years-old, or were more advanced than stage IIIA(TNM) or stage IIIa(Japanese Research Society for Gastric Cancer). Patients with colorectal cancer who were node-positive, had tumors that penetrated the serosa, were more than 60 years-old, or were more advanced than stage III(TNM), stage IIIa(Japanese Society for Cancer of the Colon and Rectum) and Dukes' C also tended to have low serum IL-12 levels. These results suggest that low serum levels of IL-12 may be observed in more advanced gastric and colorectal cancer patients. Thus, patients with low serum levels of IL-12 in gastric or colorectal cancer may require additional immunochemotherapy after surgery.

Female↗