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Biomedical subjects

T Takeda

Publications and source records attributed to T Takeda.

At least 1,531 records · Page 85Linked to original sources
PubMedDate not supplied

Neuropathological studies on strains of senescence-accelerated mice (SAM) with age-related deficits in learning and memory.

In a series of inbred Senescence-Accelerated mice (SAM) strains, accelerated-senescence prone SAMP substrains show early onset and rapid advancement of senescence. SAMP8 and SAMP10, in particular, exhibit a significant age-related deterioration in memory and learning for passive and active avoidance tasks with, respectively, a low and high incidence of systemic senile amyloidosis. In the brains of both SAMP8 and SAMP10 strains, we have found numerous morphological alterations. Here we review the changes seen in both neuronal or glial components in SAMP8/P10 brains. They may serve as markers of the neuronal degeneration leading to the deficits in learning and memory.

Aging↗
PubMedDate not supplied

Pathobiology of the senescence-accelerated mouse (SAM).

Routine postmortem examinations and the pathobiological features revealed by systematically designed studies have shown several pathologic phenotypes that are often characteristic enough to differentiate among the various SAM strains: senile amyloidosis in SAMP1, -P2, -P7, -P9, -P10, and -P11; secondary amyloidosis in SAMP2 and -P6; contracted kidney in SAMP1, -P2, -P10, and -P11; immunoblastic lymphoma in SAMR1 and -R4; histiocytic sarcoma in SAMR1 and -R4; ovarian cysts in SAMR1; impaired immune response in SAMP1, -P2, and -P8; hyperinflation of the lungs in SAMP1; hearing impairment in SAMP1; degenerative temporomandibular joint disease in SAMP3; senile osteoporosis in SAMP6; deficits in learning and memory in SAMP8 and -P10; emotional disorders in SAMP8 and -P10; cataracts in SAMP9; and brain atrophy in SAMP10. These are all age-associated pathologies, the incidence and severity of which increase with advancing age. The SAM model in which these pathobiological features have been carefully monitored will be a valuable tool in the clarification of the pathogenic mechanisms of age-associated pathologies and in the research for effective methods to modulate or ameliorate these pathologies.

Aging↗
PubMedDate not supplied

Management and design of the maintenance of SAM mouse strains: an animal model for accelerated senescence and age-associated disorders.

The Senescence-Accelerated Mouse (SAM) was established by inbreeding and pedigree selection based on the life span, degree of senescence, as well as the incidence and degree of several age-associated disorders. At first, SAM strains were developed under conventional conditions, but now some strains are also maintained under specific pathogen-free conditions. There are many methods used to maintain such strains of mice; our methods will be introduced as one example of how to develop and maintain strains of mice used in aging research.

Aging↗
PubMedDate not supplied

Enzyme-free method for cultured skin grafting.

Cultured skin autografting has promise to improve the prognosis of severe burn injury. Established methods for cultured epithelial cell autografting need enzymatic proteolytic reaction that have potential risks of losing cell surface structures and causing allergic reactions in the recipients. Therefore, we have developed an enzyme-free method of cultured skin autografting. Donor skin was obtained in 0.2-0.3 mm thickness during an operation of debriding burned eschar. The skin was cut into pieces and spread on removable soft culture surface membrane in culture plates. Modified MCDB 153 medium with 10 microg/L epidermal growth factor and 150 mg/L bovine pituitary extract was used. The tissues were incubated at 37 degrees C in a water-saturated atmosphere of 5% CO2 in air. After 3 weeks, the cultured tissue on the membrane was removed mechanically from the bottom of the plates and implanted on granulated recipient sites in upside down manner. The cultured auto-skin grafting was successfully performed in two patients with severe burn. The recipient sites were partially epithelized in 2 weeks and maintained thereafter. Our method is performed easily using partial thickness donor skin without enzymatic processes.

Adult↗
PubMedDate not supplied

Bone mineral density of metatarsus in hemiplegic subjects.

The cortical bone mineral density (BMD) of the first metatarsus was measured using computed x-ray densitometry in 84 hemiplegic subjects (35 men and 49 postmenopausal women) and 49 healthy age-matched controls (23 men and 26 postmenopausal women), and the determinants of paralysis-induced cortical osteopenia were investigated. In the hemiplegia group, ages were 63.9 +/- 9.8 yr (mean +/- standard deviation) for men and 66.6 +/- 11.0 yr for women. The duration of hemiplegia was 25.3 +/- 19.8 mo for men and 26.0 +/- 26.3 mo for women. The Brunnstrom stage (lower limb) was 4.0 +/- 1.1 for men and 3.8 +/- 1.4 for women. The walking ability, evaluated by walking score, was 3.6 +/- 1.3 (range, 1-5) for men and 3.2 +/- 1.5 (range, 1-5) for women. The time since menopause was 14.8 +/- 10.0 yr. The age and time since menopause were similar in the hemiplegia and control groups. On the paralyzed side, the BMD of men and women in the hemiplegia group was significantly lower than that of the control group on the nondominant side (by 6.1% and 11.6%, respectively). In hemiplegic men, Brunnstrom stage and walking score showed a significant positive correlation to the BMD (r = 0.418 and r = 0.349, respectively). In hemiplegic women, on the other hand, age, duration of hemiplegia, and years since menopause showed a significant negative correlation to the BMD (r = -0.260, r = -0.478, and r = -0.506, respectively), and Brunnstrom stage and walking score showed a significant positive correlation to the BMD (r = 0.526 and r = 0.406, respectively). These findings suggest that the determinant of metatarsal cortical BMD loss on the paralyzed side of the hemiplegic subject might be different according to gender. That is, although the degree of paralysis and walking ability could be a determinant of metatarsal cortical BMD loss on the paralyzed side of hemiplegic men, additional factors such as age, duration of hemiplegia, and years since menopause could play an important role in the determination of metatarsal cortical BMD loss in postmenopausal hemiplegic women.

Activities of Daily Living↗
PubMedDate not supplied

N-isopropyl-p-[123I]iodoamphetamine SPECT in MELAS syndrome: comparison with CT and MR imaging.

Regional cerebral perfusion was studied in three patients with the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, using single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine (IMP). Accumulation of the tracer was relatively decreased in the parietooccipital regions and also in the frontotemporal regions after stroke-like episodes. However, quantitative regional cerebral blood flow (rCBF) measurement showed that rCBF was relatively well preserved even at these sites, and a hyperemic state was observed at the sites of normal accumulation. IMP SPECT may be useful in the diagnosis and assessment of the progress of the MELAS syndrome.

Acidosis, Lactic↗
PubMedDate not supplied

High spatial resolution CT with a synchrotron radiation system.

OBJECTIVE: We describe a monochromatic X-ray CT system using synchrotron radiation, which has been constructed employing a vertical wiggler beam line at the National Laboratory for High-Energy Physics in Tsukuba, Japan. This CT system was produced to facilitate examination of the microstructures of material and biological specimens. MATERIALS AND METHODS: The system provides excellent contrast and has a spatial resolution capacity ranging from 2 to 100 mm. In this preliminary experiment, the images of the rat were obtained at 36-mm slice thickness and 33.2-keV X-ray energy. RESULTS: The nasal cartilage, skull, and teeth of a live rat were clearly demonstrated with 36-mm spatial resolution. CONCLUSION: Using a monochromatic X-ray CT system with synchrotron radiation, detailed structures of rat skull were imaged clearly.

Animals↗
PubMedDate not supplied

Treatment results of advanced neuroblastoma with the first Japanese study group protocol. Study Group of Japan for Treatment of Advanced Neuroblastoma.

PURPOSE: To elucidate the efficacy of intensive induction and consolidation chemotherapy regimens (Study Group of Japan for Advanced Neuroblastoma [JANB] 85) for patients with advanced neuroblastoma aged 1 year or older. PATIENT AND METHODS: One hundred fifty-seven patients with newly diagnosed advanced neuroblastoma were entered into this study between January 1985 and December 1990. Eligible patients were 12 months old or older with stage III or IV disease. The patients first received six cyclic courses of intensive induction chemotherapy (designated regimen A1) consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydro-pyranyl Adriamycin (pirarubicin; 40 mg/m2), and cisplatin (90 mg/m2). The patients were further treated with three different consolidation protocols: 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosour ea, dacarbazine, and bone marrow transplantation. RESULTS: Overall survival rates for patients with stage III disease without reference to the consolidation protocols were 80.8%, 76.9%, and 66.3% at 2, 5, and 10 years, respectively. The overall survival rates for patients with stage IV disease were 58.8%, 34.4%, and 28.9% at 2, 5, and 10 years, respectively. There were no statistically significant differences between the three consolidation treatment groups. Patients who did not achieve complete remission (CR) with induction chemotherapy and surgery all died, suggesting that CR is essential for the cure of advanced neuroblastoma. The overall 5-year survival rate of the 24 patients with N-myc amplified stage III and IV disease was 33.3%, and the longest survival time of a relapse-free patient was 103 months. CONCLUSION: The intensive induction chemotherapy regimen used in this study may be of significant value in increasing the CR rate and survival for patients with N-myc amplified and nonamplified advanced neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Erythrocyte water content in spontaneously hypertensive rats and DOCA-salt hypertensive rats.

Intra-erythrocyte water, sodium and potassium contents were measured in spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)-salt rats. In 12 week old SHR, the intra-erythrocyte water content was slightly but significantly lower than that in age-matched Wistar-Kyoto (WKY) rats. SHR also exhibited a significantly lower intra-erythrocyte potassium content, but sodium content tended to be elevated. Although sodium content was not correlated with the water content, potassium content was. In DOCA-salt hypertensive rats, the intra-erythrocyte sodium content was higher than that in age-matched normotensive Sprague-Dawley rats by about 33%, but the water and potassium contents were similar. There were no significant correlations between these parameters. These findings provide no evidence of water retention in erythrocytes from DOCA-salt rat or SHR even though intra-erythrocyte sodium content was increased.

Animals↗
PubMedDate not supplied

Gene expression of endothelin receptors in aortic cells from cyclosporine-induced hypertensive rats.

1. We examined preproendothelin-1, ETA and ETB receptor mRNA levels in aortic endothelial and smooth muscle cells from cyclosporine (CyA)-induced hypertensive rats using the reverse transcription polymerase chain reaction method. 2. Aortic endothelial preproendothelin-1 mRNA expression was about 1.5-fold higher, while that of ETB receptor mRNA was markedly decreased in CyA-treated rats compared with those in controls. 3. The expression of ETA receptor mRNA in smooth muscle cells from CyA-induced hypertensive rats was increased about two-fold over that in cells from control animals. 4. Thus, increased endothelial preproendothelin-1, and ETA receptor mRNA levels in smooth muscle cells, which are concomitant with the decrease in ETB receptor mRNA levels in endothelium, may contribute to CyA-induced hypertension in rats.

Animals↗
PubMedDate not supplied

Relationship between endotoxin antibody levels and portal systemic shunt evaluated by per-rectal portal scintigraphy.

The reasons for the high frequency of endotoxaemia in cirrhosis, whether poor liver function or abnormal portal circulation, are not known. Accurate measurement of endotoxin itself is difficult. Instead, in this study an enzyme-linked immunosorbent assay was used to measure levels of IgA, IgG and IgM antibodies to endotoxin in patients with chronic liver disease and underlying hepatic viral infection. The relationships between the results and clinical symptoms or the presence of a portal systemic shunt were investigated. The median level of IgA antibodies was not different in patients with chronic hepatitis and those with cirrhosis, and the same was found for IgM, but the median level of IgG antibodies was significantly higher in the patients with cirrhosis. When patients with cirrhosis were grouped by the presence or absence of ascites or hepatocellular carcinoma, no significant difference was observed in any of these antibody levels. However, in cirrhotic patients with varices, the level of IgG antibodies to endotoxin was significantly higher than in patients without varices. For evaluation of the portal systemic shunt, the per-rectal portal shunt index was calculated. There was a significant correlation (R = 0.431, P < 0.001) between the per-rectal portal shunt index and the level of IgG antibodies to endotoxin. That is, the degree of abnormality in the portal haemodynamics was correlated with the level of IgG antibodies to endotoxin in patients with liver disease.

Antibodies, Bacterial↗
PubMedDate not supplied

Mass screening for neuroblastoma and estimation of costs.

On the basis of epidemiological data and medical costs for patients with neuroblastoma, we have calculated the cost of mass screening for neuroblastoma with high performance liquid chromatography (HPLC) compared to the cost when it is not performed. If the sensitivity of the mass screening is 80% and 22,000 infants are screened annually the cost will be 27,809,000 yen ($191,800). If mass is not performed, the cost will be 28,446,000 yen ($196,200). The difference in cost (637,000 yen or $4,400) is fairly small. If the sensitivity is 75% and 16,500 infants are screened, the difference is also small (174,000 yen or $1,200). Therefore, mass screening with the HPLC method will not be an undue financial burden. But re-screening at an older age will be done with less financially favorable results, considering that the sensitivity may not be as high as that of the first screening and that mothers are somewhat reluctant about re-screening. The balance of the cost of mass screening by qualitative methods may also be less favorable, since the detection rate is low.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Release mechanism of endothelin-1 and big endothelin-1 after stimulation with thrombin in cultured porcine endothelial cells.

Cultured porcine endothelial cells (EC) released immunoreactive endothelin-1 (ir-endothelin-1) and big endothelin-1 (ir-big endothelin-1) into the medium in a time-dependent way. Reverse-phase high-pressure liquid chromatography coupled with radioimmunoassay showed that the major component of ir-endothelin-1 corresponded to standard endothelin-1 (1-21) and that the major component of ir-big endothelin-1 corresponded to standard big endothelin-1 (porcine 1-39). This release was strongly inhibited by cycloheximide and was, therefore, related to de novo protein synthesis. The release of greater amounts was stimulated by thrombin. The protein kinase C (PKC) inhibitors from two chemical classes, H7 and staurosporine, inhibited release following such stimulation in a relatively dose-dependent way. Neither H7 nor staurosporine affected the basal release of both endothelin-1 and big endothelin-1. Phorbol myristate acetate, which activates PKC and the Ca2+ ionophore A23187, stimulated the release of ir-endothelin-1 and ir-big endothelin-1 in a dose-dependent way, respectively. In addition, the combination of both compounds had a synergistic effect. An inactive enantiomer of phorbol ester, 4 alpha-phorbol-12,13-didecanoate had no effect on the release of ir-endothelin-1 and ir-big endothelin-1. These results suggest that cultured EC release endothelin-1 and big endothelin-1 simultaneously, and that thrombin stimulates this release by a mechanism that probably involves intracellular Ca2+ mobilization and the activation of PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMedDate not supplied

Expression of p16 and cyclin-dependent kinase 4 proteins in primary breast carcinomas.

The immunolocalization of the p16 and cdk4 proteins was investigated in 65 retinoblastoma gene product (pRB)-positive and 20 pRB-negative breast carcinomas. These proteins were expressed in similar lesions in 84.6% of the pRB-positive and 100% of the pRB-negative carcinomas. Diffuse expression of p16 was observed in 73.8 and 70.0% of the pRB-positive and -negative cases, respectively. cdk4 and p16 expression was significantly more heterogeneous in tumors of larger sizes and/or at higher stages. These findings suggest that p16 can be induced regardless of pRB status and Rb gene function in primary breast carcinoma and that it modulates the cell cycle progression in association with cdk4.

Blotting, Western↗
PubMedDate not supplied

Elevated plasma catecholamines in hypertensives with primary glomerular diseases.

Supine plasma concentration of norepinephrine (PNE), epinephrine (PE), and aldosterone (PA), plasma renin activity (PRA), and blood volume (BV) were measured in 25 normotensive and 11 hypertensive patients with biopsy-proven glomerulonephritis who had serum creatinine concentrations of less than 1.6 mg/dl, and in 20 normotensive control subjects. PNE and PE were measured according to the trihydroxyindol method using high pressure liquid chromatography. Renal clearances of p-aminohippurate (CPAH) and endogenous creatinine (Ccr) were also determined. Age, BV, and 24-hour urinary excretion of sodium were not significantly different in the three groups. Although all the measured variables were comparable between the control subjects and the normotensive nephritic patients, blood pressure, PNE, PE, PRA, and PA were significantly higher and CPAH and Ccr were significantly lower in the hypertensive nephritic patients than in the normotensive nephritic patients or the control subjects. In the pooled nephritic patients, mean blood pressure was significantly correlated with PNE (r = 0.76, p less than 0.001), PE (r = 0.34, p less than 0.05), PRA (r = 0.33, p less than 0.05), PA (r = 0.40, p less than 0.05) and CPAH (r = -0.51, p less than 0.01). Highly significant positive correlation was also observed between PNE and systolic pressure (r = 0.63, p less than 0.001) or diastolic blood pressure (r = 0.78, p less than 0.001). The results suggest that deterioration of renal function is an important factor in the development of hypertension even in non-azotemic patients with glomerulonephritis, and that increased activities of the sympathetic nervous system and the renin-aldosterone system participate, in part, in elevating blood pressure in the hypertensive nephritic patients. Mechanisms involved in the elevation of plasma concentrations of catecholamines and renal effects on the plasma catecholamines remain to be elucidated.

Adult↗
PubMedDate not supplied

Sodium loading of inner ear fluids.

A slow intracarotid infusion of hypertonic sodium chloride solution, 350 mEq/L, and potassium chloride, 5 mEq/L, was used to increase serum sodium chloride over a 90-minute period in 85 cats. A slow, steady rise in serum sodium occurred, which reached almost 208 mEq/L at the end of 90 minutes. A concomitant rise in sodium occurred in the cerebrospinal fluid and perilymph. In contrast, the sodium showed only a transient slight increase in the cochlear and vestibular endolymph. Endolymph potassium appeared to rise in order to balance out the increase in sodium concentration of the surrounding and extracellular fluids. The ratio of sodium to potassium ions in both the endolymph and perilymph compartment remained relatively constant before and after the infusion with hypertonic NaCl. After infusion, the total concentration of ions in endolymph was similar to that of perilymph. These experiments indicate that the endolymph compartment has a built-in mechanism for maintaining a low-sodium concentration while keeping ionic balance with the surrounding perilymph and serum.

Animals↗
PubMedDate not supplied

Endolymphatic sac obstruction. Biochemical studies.

Inner ear fluids were studied biochemically in guinea pigs from 1 to 16 weeks after producing endolymphatic hydrops by obstructing the endolymphatic duct. Fluid collected from beneath the footplate showed changes of 50% of the animals indicating distension of the saccule. There was an increase in potassium concentration and decrease in sodium concentration of the collected fluid, indicating a traumatic mixing of endolymph and perilymph produced by rupture of the saccule during collection of the fluid. The smallest changes occurred at one week, and the greatest changes were found four months after endolymphatic sac obstruction. Similar findings were observed in studying inner ear fluids obtained from patients with Ménière's disease. Cochlear endolymph showed biochemical alterations after endolymphatic duct blockage. There was a two- to three-fold increase in sodium concentration and a decrease in potassium concentration with the total ionic concentration remaining approximately the same. Some guinea pigs showed similar changes in vestibular endolymph. This study indicates that in the guinea pig, endolymph obtained in the distended endolymph compartment has a slightly different sodium-potassium ratio as compared to the normal ear. In patients with Ménière's disease there may also be an elevation of endolymph sodium concentration. The significance of this change and hearing loss observed in experimental endolymphatic hydrops and Ménière's disease is open to speculation at the present time.

Animals↗