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Biomedical subjects

K Ohtsubo

Publications and source records attributed to K Ohtsubo.

At least 55 records · Page 3Linked to original sources

Immunocytochemical demonstration of prolactin interaction with choroid plexus in aging and acute hyperprolactinemia.

Prolactin (PRL) exerts a direct effect on the central nervous system, reaching the PRL-responsive brain regions via cerebro-spinal fluid (CSF). The hormone enters the CSF by a specific receptor-mediated transport mechanism that is localized on the epithelium of the choroid plexus (CP) of brain ventricles. PRL interactions with the CP in aging were examined in young (3-month) and old (27-month) female Wistar rats using immunocytochemistry (immunogold technique). The enhancement of PRL uptake by the CP in animals at both ages was achieved by the modelling of acute hyperprolactinemia. A great age-related difference was found in the intensity of immunocytochemical reaction under activated conditions, the uptake of PRL by CP being significantly higher in young animals than in old. The character of the colloidal gold particle distribution in different components of CP epithelial cells appeared to be the same in both age groups. The weakening of PRL-transporting capacity in the CP of old animals may constitute one aspect of the alteration of neuroendocrine regulation in the CP-CSF system that occurs during aging.

Acute Disease↗

"Lupinosis"-like lesions in mice caused by ustiloxin, produced by Ustilaginoieda virens: a morphological study.

A crude toxin, obtained by methanol-extraction of a water extract of false smut balls (INA-KOUJI in Japanese) caused by Ustilaginoidea virens on rice panicles, was injected into mice intraperitoneally. Single injection of 100 or 200 mg/kg body weight of the extract was not lethal but caused acute, occasional necrosis of hepatocytes and renal tubular cells, followed by increased number of mitotic figures with occasional multinuclear giant cells. Erosions and ulceration of the forestomach and atrophy of the thymus were observed a week later. Repeated intraperitoneal injection of the crude toxin at the levels of 12 and 25 mg/kg body weight induced more severe necrosis of the liver and kidneys, with delayed occurrence of mitosis. Forestomach erosion also occurred. Serial injection for 10-12 days of either 3 or 6 mg/kg of the crude extract or 400 micrograms/kg of ustiloxin A, using the purified crystals, caused relatively mild but definite liver and kidney lesions similar to those described above. The lesions in the liver and kidney were quite similar to those observed in lupinosis caused by phomopsin A, a mycotoxin produced by Phomopsis leptostromiformis. Isolation of the toxic substance indicates that the contaminated rice panicles may cause toxicosis of cattle, although no field outbreaks have occurred yet.

Animals↗

Computer-aided 3-dimensional visualization of abdominal aortic aneurysms from CT images.

A new method for elucidating the process of abdominal aortic aneurysm enlargement is presented herein. First, 3-dimensional (3-D) reconstructed images were used to precisely evaluate the size of an aneurysm, after which reconstruction and a volume analysis of images were performed with a personal computer system using serial computed tomographic films. The evolution of an aneurysm was examined by the detailed reconstruction, and an estimation of size was achieved by accurately measuring the figure reconstructed from the angle perpendicular to the axis of the contour. In quantifying the enlargement of an aneurysm, an exact evaluation of volume changes and morphological changes can be performed using the 3-D reconstruction method from the film series obtained at follow-up studies. The volume analysis proved especially useful for evaluating the axial expansion of aneurysms with stable maximum diameters.

Aortic Aneurysm, Abdominal↗

CELSS: possible contributions to earth science program and others.

CELSS technology, composed of various subsystems designed to stabilize the environment in closed space can be used to construct the Closed Ecology Experiment Facility. The Closed Ecology Experiment Facility has the character of an Environmental Time Machine. Many environmental researches of studies will, it is proposed, be conducted using this facility. The concept of Closed Ecology Experiment Facility is described, and several research items related to earth science potentially to be conducted using this facility are indicated. As an example of the application, an improved model of climate estimation is discussed.

Animals↗

Measurement of rice crop metabolism using closed-type plant cultivation equipment.

In order to determine a required plant cultivation area which can sustain human life in a closed environment, the material circulating measurement system including a Closed-type Plant Cultivation Equipment (CPCE) in which the metabolic data of plants can be accurately measured has been constructed. According to results from cultivation experiments using rice, the harvest index was 29.9% for 110 days, and the required crop area to supply food, oxygen and water for one person was calculated to be about 111m2, 36m2 and 0.9m2, respectively.

Air Conditioning↗

Effects of neonatal administration of zearalenone on the reproductive physiology of female mice.

The effects of neonatal (1-10 days) administration of various doses (5-30 micrograms/animal) of zearalenone, a mycotoxin, on the sexual maturation and reproductive physiology of female ICR mice were investigated. The drug was found to have mimic estrogen actions, causing delayed vaginal opening, persistent estrus (60-80% incidence) and sterility. Daily doses of zearalenone (10-30 micrograms/animal) for 3-5 neonatal days resulted in infertility accompanied by thickening of the vaginal epithelium, even after ovariectomy and adrenalectomy, indicating mucosal independence of endogenous estrogen. Thus, it may be possible that zearalenone acts by binding irreversibly to estrogen receptors in the target tissues.

Adrenalectomy↗

Recombinant human granulocyte colony-stimulating factor accelerates regeneration after T-2 toxin-induced hemopoietic injury and lessens lethality in mice.

The effects of rhG-CSF on T-2-induced leukopenia and lethal toxicity in mice were investigated. First, T-2 was administered by gavage to adult male mice at a dose of 3 mg/kg b.w. daily for 7 days, and rhG-CSF was given i.p. in daily dose of 10 or 30 micrograms/kg b.w./day, beginning on the 2nd day, for 5 days. The peripheral WBC of mice receiving T-2 alone was decreased to one fourth of control counts, and bone marrow (BM) cell counts were also markedly diminished. The administration of rhG-CSF prevented those T-2-induced depressions. Histologically, the delation of the hematopoietic cells from BM and spleen of mice given T-2 was remarkably counteracted by administration of rhG-CSF. In the other experiment, rhG-CSF was injected i.p. for 5 days beginning on the next day of the 7-day T-2 administration. The recovery of WBC and BM cell counts was hastened by rhG-CSF reaching the control level in 6 days, and differential leukocyte analysis revealed an increase of neutrophils. Furthermore, simultaneous administration of rhG-CSF depressed the T-2-induced lethal toxicity, dose-dependently. The results revealed that rhG-CSF possesses a potent ability to protect T-2-induced leukopenia and lethality in mice, and it could be as an antidote against T-2 and related trichothecene-induced acute intoxication.

Animals↗

The amino acid sequence of a 20 kDa bifunctional subtilisin/alpha-amylase inhibitor from bran [correction of brain] of rice (Oryza sativa L.) seeds.

A 20 kDa bifunctional inhibitor of the microbial proteinase, subtilisin, and the alpha-amylase from the larvae of the red flour beetle (Tribolium castaneum) was purified from bran of rice seeds by saline extraction, precipitation with ammonium sulphate, ion-exchange chromatography on DEAE-Cellulose and Toyopearl CM-650, and preparative HPLC on Vydac C18. The complete primary structure was determined by automatic degradation of the intact, reduced and S-alkylated protein, and by manual DABITC/PITC micro-sequencing of peptides obtained from the protein following separate enzymic digestions with trypsin, pepsin, chymotrypsin, elastase and the protease from S. aureus V8. The protein sequence, which contained 176 residues, showed strong homology with similar bifunctional inhibitors previously isolated from wheat and barley which are related to the Kunitz family of proteinase inhibitors from legume seeds.

Amino Acid Sequence↗

Influence of food on serum ambenonium concentration in patients with myasthenia gravis.

Influence of food on the serum concentration and kinetics ambenonium chloride (AMBC) has been examined in thirteen patients with myasthenia gravis (MG). Mean serum concentrations and Cmax during fasting were higher than those in the non-fasting state. The AUC (0-3 h) was also about four-times larger. The drug effects versus the serum concentration were observed to be anti-clockwise or clockwise. The effective range of the Cmax varied between patients. The unexpected increase in Cmax led to adverse muscarinic actions of AMBC, when the condition was changed from the nonfasting to the fasting state. It is recommended that the dose be changed during non-fasting treatment when adjusting the optimum regimen for patients myasthenia gravis. Patients must be advised to keep to the dosing and dietary schedule in order to avoid unexpected adverse actions to AMBC.

Adult↗

Ultrastructure appearance of atherosclerosis in human and experimentally-induced animal models.

We describe here the basic structure of the aorta, the changes with aging and ultrastructural appearance of atherosclerosis of human and animal models. The architecture of the aortic wall is highly organized, for adaptation to changes of blood pressure. The main cells composing the vessel are endothelial cells and smooth muscle cells. They maintain the integrity and homeostasis of the aorta along with the extracellular matrix of collagen fibrils, elastic fibers and glycosaminoglycans. The structural changes with aging and atherogenesis are a compensative or degenerative phenomenon caused by many factors. Three major cells are the endothelial cell, smooth muscle cell and monocyte-derived macrophages (as well as platelets) all of which are involved in atherogenesis. Foam cells in atheromatous lesions are derived from macrophages and smooth muscle cells. Recently, the molecular biological nature and function of these cells and their derived-factors have been thoroughly investigated in cell culture and in experimental animal models caused by a mechanical injury of the endothelium or by a dietary induced hypercholesterolemia. However, the mechanism of the endothelial injury in vivo as well as formation of atheromatous cores of human atherosclerosis is not exactly understood. Some structural and functional changes inherent to the arterial wall during aging may play an important role in initiation or progression of human atherosclerosis.

Aging↗

[Age-related non-tumorous lesions in SPF C57BL/6 mice with special reference to amyloidosis].

Non-tumorous pathological changes in C57BL/6 CrSlc mice, which were reared under a barrier system and died spontaneously, were examined. At 3 months intervals 125 to 209 mice were purchased at 4 weeks of age and raised for the supply of aged animals. A large portion of the mice were used for various experiments between 3 and 30 months of age, while not a small number died spontaneously and were autopsied. The major non-neoplastic lesion was amyloidosis, with incidence of 55.5% and 74.4% for the autopsied female and male, respectively. The organs involved were the liver, kidneys, spleen, adrenal glands, ileum, heart and lungs. Skin ulceration and its scar, cerebral vascular calcification, glomerulosclerosis and sepsis in both sexes, distension of the seminal vesicles in males, fibroblast growth of the adrenal glands in females were commonly found. Incidence of spontaneous neoplastic lesions was 69.7% and 55.1% for the female and male, respectively.

Aging↗

[Age-related incidence of spontaneous tumors in SPF C57BL/6 and BDF1 mice].

Incidence of spontaneous tumors in C57BL/6 NCrj (CR), C5BL/6 CrSlc (SL) and B 6 Crj x DBA/2 NCrj F1 (BD) mice, which were reared under a barrier system and died natural death, were examined. Cohorts of mice in 200 to 300 each were purchased at 4 weeks of age and raised under SPF conditions. A large portion of the mice were used for various experiments between 3 and 30 months old while not a small number died before use and were autopsied. Median survival periods of the female and male were estimated at 697 and 680 days for CR, 764 and 806 days for SL and 866 and 929 days for BD, respectively. Incidence of spontaneous neoplastic lesions in the autopsied animals were 77.4% and 79.2% of 535 female and 590 male CR, 69.7% and 55.1% of 502 female and 463 male SL, and 75.8% and 78.0% of 298 female and 346 male BD, respectively. In CR, histiocytic sarcoma was the most predominant tumor, accounting for 72.1% of all tumors. In SL, malignant lymphoma was the most prevailing, forming 62.3%, and, in male BD, hepatocellular carcinoma was the most frequent, accounting for 41.8% of all tumors.

Aging↗

The use of t-butyl alcohol in the microdissection of resin corrosion casts for SEM.

We developed a new method using t-butyl alcohol in the microdissection of microvascular resin casts of the rat cerebral cortex for scanning electron microscopy. Brains injected with Mercox resin were eroded with sodium hypochlorite solution and dehydrated with graded ethanol. The resin casts obtained were embedded and frozen in t-butyl alcohol at 4 degrees C, and shaved through the planes of interest parallel to the brain surface with a razor blade. The sections were directly freeze-dried and coated with gold and platinum for scanning electron microscopy. Our method enables the demonstration of cross sections of the fine microvascular networks by SEM without any contamination or mechanical artifacts such as distortion and destruction.

Animals↗

Elucidation of three-dimensional ultrastructure of Hirano bodies by the quick-freeze, deep-etch and replica method.

To clarify the yet controversial fine structure of Hirano bodies, we made three-dimensional observations of the tissues from the right hippocampus obtained at autopsy of elderly patients by the quick-freeze, deep-etch and replica method. The basic structure of Hirano bodies was a unit lamella, a closely attached pair of sheets composed of parallel-running smooth filaments, 10 to 12 nm in diameter with 12-nm interspaces. In the unit lamella, filaments from each of the overlapping sheets crossed obliquely at acute or obtuse angles to form lattice-like meshworks. The unit lamellae were arranged in a folded, waved or concentric manner, and connected or supported by cross-linking filaments of the same width. The distance between these unit lamellae was about 50 nm. Occasionally the sheets were separated or fused making layers of one to three sheets. At the periphery of the bodies parallel filaments were dispersed into individual filaments of similar size or directly attached to the cytoplasmic membrane.

Aged↗

The histopathology of the liver in older patients with hepatitis B virus surface antigenaemia.

The histopathology of the liver and the detectability of intrahepatic hepatitis B virus (HBV) markers were studied in 34 autopsy cases in elderly patients (mean age 73.9 years, range 60-91 years) who had had a history of positive HBV surface antigenaemia prior to death. Seven of 14 persistent HBV carrier cases (group A) in which long-lasting HBV surface antigen (HBsAg) carriage in the sera had been confirmed by sequential assays, and 5 out of 15 HBV-infected people (group C, single assay) showed significant primary liver damages including chronic hepatitis, toxic hepatitis, liver cirrhosis and hepatocellular carcinoma. In 5 cases (group B), one of which was type B liver cirrhosis, HBsAg became negative and HBsAb appeared during the follow-up period (up to 33 months). Among confirmed HBV carriers, HBsAg and HBV core antigen were most frequently found in the liver of cirrhotic cases with and without hepatocellular carcinoma (5 of 6), whereas these were rarely detected in those with non-specific changes or slight hepatitic activity (1 of 7). All 5 cases in group B were negative for histological HBV-related antigens and the findings in group C were variously interpreted. Post-mortem cases of the aged HBV carriers who survived their mean life expectancy represent an important population in which to study the natural history of HBV carriers.

Aged↗

Paired twisted filaments in human pinealocytes.

Paired twisted filaments (PTF) have been confirmed and described ultrastructurally in the normal human pineal gland for the first time. The PTF showed a peculiar double helical structure, measuring 12 to 25 nm in maximal helix width with a half-periodicity of 30 to 35 nm (periodicity of the constrictions). Each filament was about 10 nm wide. The PTF formed parallel aggregates in the perikaryotic cytoplasm of the pinealocytes. In 8 of 12 autopsied middle-aged to elderly individuals, the PTF were present in a small proportion of pinealocytes. The identity of the PTF remains unclear in terms of their apparent similarity to the paired helical filaments observed previously in aged rats. However, the age distribution of individuals with PTF suggests that the intermediate filaments of human pinealocytes are more susceptible to early deterioration during aging than those of other cerebral neurons.

Actin Cytoskeleton↗

Effect of long-term feeding of nivalenol on aflatoxin B1-initiated hepatocarcinogenesis in mice.

Nivalenol, a trichothecene, occurs widely in cereals and foods; our current two-year feeding trial has revealed no tumorigenic activity in female mice. To investigate whether dietary nivalenol modulates the development of aflatoxin B1 (AFB1)-initiated hepatocarcinogenesis, one-week old C57Bl/6 x C3H F1 mice were injected intraperitoneally with 6 mg/kg bw AFB1 and six weeks later fed diets containing 0, 6 or 12 ppm nivalenol for one year. Male mice in all three groups developed hepatocellular carcinomas and adenomas, while the incidences in females were 31% in those given AFB1 alone and 20% and 0 in those given AFB1 with 6 and 12 ppm nivalenol, respectively. These findings indicate that dietary nivalenol suppresses AFB1-initiated hepatocarcinogenesis in female mice, presumably by acting on the promotion step.

Aflatoxin B1↗

[Evaluation of the intra-hepatic arterial injection therapy of cisplatin (CDDP)-lipiodol suspension in a child with hepatoblastoma].

Treatment, beginning in November 1986, of chemotherapy with cisplatin (CDDP) was given to a 4-year-old girl with unresectable hepatoblastoma. Laparotomy for excision was performed after 16 months of therapy. The solution of CDDP was administered by dropping intravenously (DIV therapy) or intrahepatic arterially (IA therapy), and a suspension of crystalline CDDP with Lipiodol containing phosphatidylcholine was injected intrahepatic arterially (CDDP-suspension therapy). To evaluate the safety and effect of CDDP-suspension therapy in this case, toxicity and antitumor effect were investigated by comparison with DIV therapy. Under chemotherapy with CDDP, logarithm of alpha-fetoprotein reduced linearly. When a slope (k) of the regression line was defined as a constant of AFP reduction rate, k was -0.0072. AFP reduction rate under CDDP-suspension therapy (k = -0.0097, 12/1987-6/1988) was more rapid than that under DIV therapy (k = -0.0053, 2/1987-12/1987), and AFP reduced completely in June of 1988. The CDDP-suspension therapy may be suggestive of more effective treatment. Platinum (Pt) concentration in serum, urine and hepatic specimens was determined in order to investigate CDDP pharmacokinetics. The area under serum concentration (AUC) per doses and renal elimination rate were lower values under CDDP-suspension therapy. In the hepatic specimen, Pt concentration was significantly higher at the site where Lipiodol was localized. These results suggested that CDDP-suspension therapy delayed CDDP distribution and reduced toxicity. After CDDP-suspension therapy, reversible toxicity to the liver was observed. However, that to kidney or to blood components was less severe than after DIV therapy. After multiple DIV therapy, serum creatinine and blood urea nitrogen increased gradually in the course of therapy, while they tended to recovery after multiple CDDP-suspension therapy.

Carcinoma, Hepatocellular↗