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Biomedical subjects

K Morimoto

Publications and source records attributed to K Morimoto.

At least 361 records · Page 20Linked to original sources

Antiepileptogenic action of 7-chlorokynurenic acid on amygdala kindling of rats.

To investigate the role of strychnine-insensitive glycine receptors in epilepsy, we studied the effects of 7-chlorokynurenic acid (7-CK), a selective strychnine-insensitive glycine receptor antagonist, on amygdala kindling development and previously amygdala-kindled seizures in rats. ICV administration of 7-CK (10 or 20 micrograms) suppressed amygdala kindling development, according to the motor seizure stage and afterdischarge development, in a dose-dependent manner. However, 7-CK had no significant effect on previously kindled seizures at either of these doses nor did 20 micrograms at any time (15 min, 30 min, 2 h, and 24 h) after injection studied. These results demonstrate that this selective strychnine-insensitive glycine receptor antagonist has antiepileptogenic activity and suggest a role for the glycine receptors in the contribution of the NMDA receptor complex to epileptogenic events.

Amygdala↗

Single-step purification of F(ab')2 mu fragments of mouse monoclonal antibodies (immunoglobulins M) by hydrophobic interaction high-performance liquid chromatography using TSKgel ether-5PW.

A procedure is described for preparation and single-step purification of F(ab')2 fragments, herein designated as F(ab')2 mu' from mouse monoclonal antibodies of the IgM class. Hydrophobic interaction high-performance liquid chromatography (HPLC) using TSKgel Ether-5PW was well applicable to the purification. The IgM was digested with pepsin at the pepsin-to-IgM ratio of 1:200 (w/w) in 100 mM citrate buffer (pH 4.2) at 37 degrees C for 2 h. The digests were applied to the gel equilibrated with the buffer containing 1 M ammonium sulfate. F(ab')2 mu fragments were adsorbed onto the gel with the same buffer, and eluted by reducing the ammonium sulfate concentration to 0 M. The fraction containing F(ab')2 mu fragments was homogeneous (purity higher than 97%) by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel-filtration HPLC. The recovery of the antigen-binding site was 55-72%. The cycle time of the Ether-5PW HPLC was 40 min, and up to 98 mg F(ab')2 mu fragments. The molecular mass of F(ab')2 mu was estimated to be 144-146 kDa. In comparison with IgM, F(ab')2 mu lost entirely the complement C1q binding activity, and the sugar content was greatly reduced. The binding of IgM with non-specific proteins turned to be negligible, when IgM was converted to F(ab')2 mu, suggesting that the fragments are useful for immunological application.

Animals↗

A review of the genotoxicity of 1-ethyl-1-nitrosourea.

1-Ethyl-1-nitrosourea (ENU) is a potent monofunctional ethylating agent that has been found to be mutagenic in a wide variety of mutagenicity tests system from viruses to mammalian germ cells. It also has been shown to induce tumors in various organs of mammals. ENU has been used only for research purposes. ENU possesses the dual action of ethylation and carbamoylation. The ethyl group can be transferred to nucleophilic sites of cellular constituents, and the carbonyl group can be transferred to an amino group of protein. ENU is able to produce significant levels of alkylation at oxygens, such as the O6 position of guanine and the O4 position of thymine of DNA. The molecular genetic data obtained from ENU-induced mutants on various species suggest that ENU produces mainly GC-AT transitions and, to a small extent, AT-GC, AT-CG, AT-TA, GC-CG and GC-TA base substitutions. This mutation spectrum of ENU is different from that of 1-methyl-1-nitrosourea, which mainly induces GC-AT transitions. ENU is a most potent mutagen in mouse germ cells, especially in stem-cell spermatogonia. It induces intragenic mutations with high frequency in male mouse germ cells. ENU has been established as a model compound for exploring the effects of chemical mutagenesis on mouse germ cells.

Animals↗

Dipeptide transport across rat alveolar epithelial cell monolayers.

The transepithelial transport and metabolism of two model peptides, glycyl-D-phenylalanine (Gly-D-Phe) and glycyl-L-phenylalanine (Gly-L-Phe), across primary cultured monolayers of rat alveolar epithelial cells were studied. These tight monolayers (> 2000 omega-cm2) exhibited type I pneumocyte morphological and phenotypic characteristics. A reverse-phase HPLC was used to monitor the appearance of parent dipeptides and their metabolites (D- or L-Phe) in the receiver fluid. The apparent permeability coefficient (Papp) for Gly-D-Phe was about 1.6 x 10(-7) cm/sec at both 1 and 10 mM and in both the apical-to-basolateral (AB) and the basolateral-to-apical (BA) directions. In contrast, the Papp of Gly-L-Phe at 1 mM was about two times higher than that at 10 mM in the AB direction. The Papp of Gly-L-Phe in the BA direction at either concentration was about the same (about 1.4 x 10(-7) cm/sec). Whereas no metabolite was detected during Gly-D-Phe transport, the proportions of a metabolite, L-Phe, observed at 4 hr in the basolateral receiver fluid for 1 and 10 mM apical donor Gly-L-Phe accounted for 83 and 77% of the estimated total Gly-L-Phe (i.e., L-Phe+Gly-L-Phe), respectively. The corresponding values in the BA direction were 40 and 19% of the estimated total Gly-L-Phe in the apical receiver reservoir. Metabolism of Gly-L-Phe was significantly reduced in the presence of 3 microM actinonin (an inhibitor relatively specific for aminopeptides M) in the apical but not the basolateral fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increased formation of 8-hydroxydeoxyguanosine, an oxidative DNA damage, in lymphoblasts from Fanconi's anemia patients due to possible catalase deficiency.

Fanconi's anemia (FA) cells are highly susceptible to both reactive oxygen species and mitomycin C (MMC), a DNA cross-linking agent. In this study we have determined the amounts of 8-hydroxydeoxyguanosine (8OHdG), typical of oxidative DNA damage, in Epstein-Barr virus transformed lymphoblasts from FA patients and normal controls by the use of HPLC combined with electrochemical detection. FA cells (HSC72 and 99 cells being assigned to FA complementation group A) formed 2-3 times more 8OHdG than control cells after incubation with 20 mM H2O2 at 37 degrees C for 30 min. FA cells also formed more 8-hydroxyguanosine, typical of oxidative RNA damage, than control cells. FA cells showed decreased activity to decompose H2O2. Although the activity in FA cells was only 20-30% less than control cells, the remaining, undecomposed H2O2 concentration was almost twice as much in FA cells as in control cells, and the remaining H2O2 concentration correlated well with the amounts of 8OHdG formation. The H2O2 decomposing activity was almost completely inhibited by sodium azide (NaN3) or aminotriazole, both catalase inhibitors. With these inhibitors the amounts of 8OHdG formation were much higher than in those cells without inhibitors, and were almost the same in control cells as in FA cells. Catalase activity in FA cell lysates was 70-80% of controls. MMC also increased 8OHdG formation in FA cells only at ED100 but not at ED50. These results indicate that FA cells, at least FA complementation group A cells, have increased susceptibility to oxidative DNA damage, and that this increased susceptibility is possibly due to decreased catalase activity. These results also suggest that catalase plays an important role in protecting DNA from oxidative damage. However, this increased susceptibility to oxidative DNA damage is considered not to be the major cause of the increased susceptibility to MMC.

8-Hydroxy-2'-Deoxyguanosine↗

Effect of lifestyle on levels of specific IgE antibodies.

Specific IgE antibodies against cobalt-conjugated human serum albumin (Co-HSA) were determined in serum samples from 706 hard metal workers who responded to a questionnaire on 17 physical and mental health practices. Hard metal (an alloy of cobalt) exposure resulted in significant (P < 0.05) increases in Co-HSA RAST indices in male subjects. In contrast, no factor concerning health practices made an independent contribution to elevation or suppression of specific IgE levels against cobalt. Although total IgE level was found to be significantly (P < 0.01) modulated by the cumulative health practice index (HPIA: Health Practice Index in Allergic reaction), which was extracted by MANOVA analysis while controlling for sex, age, and environmental factors, no significant association was found between HPIA and specific IgE level against cobalt. Multiple logistic analysis also revealed that health practices and hard metal exposure had a significant relative risk (> 2.3; P < 0.05) of elevating Co-HSA RAST index when the total IgE level was more than 400 IU/ml. Thus, a healthy lifestyle as well as discouragement of occupational exposure may be of benefit in reducing allergic disorders for persons with high IgE levels.

Adult↗

The central role of corticotrophin-releasing factor (CRF-41) in psychological stress in rats.

1. We investigated the central role of corticotrophin-releasing factor (CRF-41) in psychological stress-induced responses, including cardiovascular, thermoregulatory and locomotive activity in free-moving rats. 2. Psychological stress was induced by cage-switch stress. After rats were placed in the novel environment, blood pressure, heart rate, body temperature and locomotive activity significantly increased. The intracerebroventricular (I.C.V.) injection of alpha-helical CRF(9-41), a CRF-41 receptor antagonist, significantly attenuated the stress-induced hypertension, tachycardia, hyperthermia and increase in locomotive activity. However, in unstressed rats, the I.C.V. injection of alpha-helical CRF(9-41) had no effect on physiological parameters measured in this study. 3. In unstressed rats, the I.C.V. injection of CRF-41 (1 microgram and 10 micrograms) increased blood pressure, heart rate, body temperature and locomotive activity in a dose-dependent manner. The changes in these responses were quite similar to those observed during cage-switch stress. 4. The results suggest that central CRF-41 plays an important role in psychological stress-induced hypertension, hyperthermia, tachycardia and increase in locomotive activity. However, it is likely that central CRF-41 does not contribute to normal cardiovascular and body temperature regulation when rats are free from stress.

Animals↗

Effects of alpha- and beta-adrenergic antagonists on rise in body temperature induced by psychological stress in rats.

We investigated the effects of intraperitoneal injection of alpha- and beta-adrenergic antagonists on psychological stress-induced responses in free-moving rats. Psychological stress was induced by immersion in 2-cm-deep water. The intraperitoneal injection of the alpha-adrenergic blocker, phentolamine (10 mg/kg), attenuated the stress-induced rise in body temperature and hypertension but enhanced tachycardia. In contrast, intraperitoneal injection of the beta-adrenergic blocker, propranolol (1 mg/kg), suppressed tachycardia but had no effect on rise in body temperature and hypertension during stress. The intraperitoneal injection of both blockers had no effect on the increase in metabolic rate (O2 consumption) induced by stress. The intravenous injection of propranolol (1 mg/kg) suppressed the stress-induced rise in body temperature. We then examined the effect of intracerebroventricular injection of propranolol on the stress-induced rise in body temperature and found that intracerebroventricular injection of propranolol (50 micrograms) suppressed the stress-induced rise in body temperature. These results support the following hypotheses: 1) Systemic injection of phentolamine suppresses the psychological stress-induced rise in body temperature by facilitating heat-loss; 2) Peripheral beta-adrenergic stimulation probably does not contribute to psychological stress-induced rises in body temperature; and 3) central beta-adrenergic receptors are important in stress-induced increases in body temperature.

Adrenergic alpha-Antagonists↗

MR angiography of renal cell carcinoma.

Seventeen patients with renal cell carcinoma were studied to evaluate the usefulness of gradient echo (fast low-angle shot), time-of-flight magnetic resonance (MR) angiography under breath-holding. By reconstruction of the data of consecutive coronal scans of the abdomen, in all 17 patients with renal cell carcinoma, MR angiography can delineate the abdominal aorta, inferior vena cava and renal arteries and veins simultaneously without any contrast materials. Our present study suggested that MR angiography is a useful imaging method for preoperatively assessing spacial vascular structures of the abdomen of patients with renal cell carcinoma.

Adult↗

An inquiry into the relationship between job strain and blood pressure in male white-collar workers.

We conducted a cross-sectional study to investigate the relationship between psychological load and blood pressure using white-collar male employees of a company located in an urban area in June, 1991. Excluding those with diseases which might induce hypertension or those under 20 yr and over 60 yr of age, 570 male subjects were eligible for analysis. Logistic regression analysis was applied to 461 subjects excluding 109 who showed unstable blood pressure level; the dependent variable was blood pressure class which contained 386 normotensives and 75 hypertensives. The explanatory variables were age, obesity, alcohol intake, cigarette smoking, habitual physical exercise, all well-known factors affecting blood pressure level, working time, commuting time, paid annual leave, and type of living (with family or alone) as objective workload, and Karasek's job strain as psychological workload. Odds ratio of job strain was statistically significant after adjusting for the foregoing factors, but in the case of high job strain, the prevalence of hypertension was low. Theorell has pointed out that contrary to the usual recognition those having a family history of hypertension tended to have a non-complaining life attitude and this indication seems to be the reason for the results of this analysis. Blood pressure is one of the most important problems in the field of industrial health and because of our highly industrialized society, it is necessary to consider psychological workload. Longitudinal observations which take into account psychological workloads must be planned, and personal traits represented by a family history of hypertension should be always taken into consideration.

Adult↗

[Effects of lifestyle on hematologic parameters; I. Analysis of hematologic data in association with smoking habit and age].

The effects of smoking and age on the results of hematologic tests were determined in a group of 429 healthy male workers. The results obtained were as follows: 1) The values of total leucocyte count (x10(9)/l), neutrophil count (x10(9)/l), lymphocyte count (x10(9)/l), monocyte count (x10(9)/l), hemoglobin (g/l), hematocrit, mean corpuscular volume (MCV; fl), mean corpuscular hemoglobin (MCH; pg), and mean corpuscular hemoglobin concentration (MCHC; g/dl) in current smokers were significantly higher than those in non-smokers. 2) Total leucocyte counts and neutrophil counts significantly increased with the number of cigarettes smoked per day in current smokers. 3) Total leucocyte counts, neutrophil counts, and lymphocyte counts significantly increased with Brinkman Index (B.I.) in current smokers. 4) The increase of age was significantly associated with the decrease of erythrocyte counts and the increase of MCV in both current smokers and non-smokers.

Adolescent↗

Effects of bed rest on bone metabolism in patients with femoral neck fracture.

The effect of continuous 1 week bed rest during traction on bone metabolism were studied in patients with femoral neck fracture. Bone demineralization was assessed by measuring serum calcium (Ca), phosphorus (P), and alkaline phosphatase (AlkP) before, during, and after 1 week-bed rest with skeletal traction. In addition, 24-hour urinary excretion of calcium and phosphorus were measured. Serum Ca did not change significantly before, during, and after bed rest, whereas serum P increased after 1 week bed rest and postoperatively remained significantly elevated. Serum AlkP did not increase with bed rest, but became elevated postoperatively. Urinary Ca excretion increased from 105.8 +/- 15.2 to 138.0 +/- 15.4 mg/24h after 1 week of bed rest, and remained elevated postoperatively. In contrast, urinary P excretion initially increased 495.1 +/- 65.0 to 610.8 +/- 87.7 mg/24h, and subsequently decreased to a level significantly less than the admission level. These results suggest that 1 week bed rest for the patients with femoral neck fracture resulted in bone atrophy and demineralization.

Aged↗

Two-step procedure for early neonatal surgery of fetal hydrocephalus.

This retrospective study analyzed the diagnosis and treatment of 36 infants with central nervous system anomalies diagnosed antenatally by ultrasonographic studies between December, 1987 and December, 1990. Magnetic resonance imaging of the fetuses without maternal or fetal sedation/anesthesia was very useful, as the fetal ventricular system was depicted clearly. Twenty-three infants with hydrocephalus underwent early postnatal surgical emplacement of a miniature Ommaya's reservoir. Continuous cerebrospinal fluid aspiration was combined with intracranial pressure monitoring. Observation of the ventricular size used ultrasonography through the anterior fontanelle. This technique controlled the intracranial pressure during the early neonatal period without serious complications. A ventriculoperitoneal shunt was emplaced 1 month later as the second, more permanent treatment. This two-step procedure achieves brain reconstitution and prevents irreversible neurological damages. Clinical and radiographic findings are presented to illustrate the effectiveness of this approach.

Brain↗

[Clinical study of children with nasal allergy].

Possible factors influencing nasal allergy in children were studied using a questionnaire and allergic examination including eosinophil count of nasal discharge, IgE RAST score to house dust and provocation test. We investigated three groups of children according to the results of allergic examinations. The negative group, the equivocal group and the definite group, respectively, consisted of 40, 49 and 107 children. We found the prediction value of definite group with eosinophil count of nasal discharge, IgE-RAST score and provocation test to house dust were respectively 77.0, 89.2 and 78.1%. Bottle feeding and history of asthma bronchiale occurred more frequently in the definite group. These observations provide epidemiologic and clinical bases for further investigations of children with nasal allergy.

Adolescent↗

[A statistical analysis of sudden deafness].

The present study was carried out in order to determine factors which influenced the prognosis of sudden deafness and to try to predict the prognosis of sudden deafness, analyzed statistically by multivariate analysis. A total of 143 patients with sudden deafness diagnosed and treated at the department of otolaryngology, Ebetsu Municipal General Hospital and Obihiro Kohsei Hospital between 1986 and 1991, were selected for this study. Statistical analysis disclosed the following. 1. A good hearing level at the initial visit, a low-frequency hearing loss, the absence of vestibular symptoms and an initial visit within seven days after onset, indicate a good prognosis for sudden deafness. 2. Multivariate analysis showed that the hearing level at the initial visit most strongly influences sudden deafness, followed by the number of days from onset to initial visit, vestibular symptoms and the difference between low- and high-frequency hearing level, in that order. 3. Furthermore, multivariate analysis showed that the prognosis of sudden deafness can be predicted at a level of 78.3%, considering the above four factors. This facilitates treatment of patients with sudden deafness.

Adolescent↗

Insulin-like growth factor-I ameliorates transient ischemia-induced acute renal failure in rats.

Acute renal failure in rats was induced by transient occlusion of bilateral renal arteries and veins to investigate whether insulin-like growth factor-I (IGF-I) has an effect on the damaged renal function or not. Administration of IGF-I at 0.01, 0.1 and 1 mg/kg by s.c. injection caused a 18.7, 33.0 and 66.5% increase of glomerular filtration rate and 54.8, 61.2 and 84.1% decrease of blood urea nitrogen, respectively, compared with the values in the saline-treated group 2 days after ischemia. Other renal parameters tested such as fractional excretion of sodium, N-acetyl-beta-D-glucosaminidase and tubular reabsorptance of phosphorus which are thought to represent renal function of proximal and distal tubules, respectively, were also improved by IGF-I treatment. A histochemical study also supported these observations. Severe epithelial necrosis of proximal tubules and decrease of brush borders were observed 2 days after transient ischemia in the saline-treated group, whereas marked histochemical alterations were not observed in the IGF-I-treated group. L-NG-nitroarginine, an inhibitor of nitric oxide synthetase, prevented the improvement of glomerular filtration rate and blood urea nitrogen by IGF-I at 1 mg/kg, suggesting that the ameliorative action on renal function by IGF-I is mediated via nitric oxide, possibly its vasodilating action. These findings provide the first evidence for the efficacy of IGF-I in the model of acute renal failure, suggesting that IGF-I may be useful for the treatment of acute renal failure.

Acute Kidney Injury↗