Search PubMed⌕ Search

Biomedical subjects

K Ohtsubo

Publications and source records attributed to K Ohtsubo.

At least 73 records · Page 4Linked to original sources
PubMed1990

Three-dimensional structure of Alzheimer's neurofibrillary tangles of the aged human brain revealed by the quick-freeze, deep-etch and replica method.

The three-dimensional structure of Alzheimer's neurofibrillary tangles in the pyramidal cells of the hippocampus and in the nerve cells of the parahippocampal gyrus was examined by the quick-freeze, deep-etch and replica method. The tangles consisted of either parallel bundles of or randomly arranged paired helical filaments (PHF), occupying the perikaryotic cytoplasm and extending to the dendritic processes. On the stereophotographs the PHF, measuring 28 to 36 nm in width, had two component filaments of 14 to 18 nm in diameter which were coiled anti-clockwise (left-handed) around each other with periodicity of 70 to 90 nm. The PHF in compact parallel bundles were cross-linked to each other with thin filaments, of about 6 nm in diameter, at relatively regular intervals. Randomly arranged PHF had no cross-bridges or side arms. Straight-type tangles of about 24 nm in diameter were rarely found in the dendritic processes. There were no discernible differences between the PHF of the patients with senile dementia of Alzheimer type and those of nondemented brains.

Aged↗
PubMed1990

Curly fibers are tau-positive strands in the pre- and post-synaptic neurites, consisting of paired helical filaments: observations by the freeze-etch and replica method.

The ultrastructure of the curly fibers was examined by the transmission and immunoelectron microscopy as well as by the rapid-freeze, deep-etch and replica method. The curly fibers consisted mainly of paired helical filaments (PHF) in the neuropils, both pre- and post-synaptic. On the deep-etch replicas, PHF in the neurites had similar dimensions to those of Alzheimer's neurofibrillary tangles in the nerve cell somata, having the width of 28 to 36 nm. The two component filaments, 14 to 18 nm in width, were twisted left-handedly with about 70- to 90-nm intervals. There were also cross-bridging fibrils of about 6 nm in diameter connecting the neighboring PHF.

Aged↗
PubMed1990

Alzheimer's neurofibrillary tangles and paired helical filaments in the pheochromocytoma cells of the adrenal medulla--electron microscopic and immunoelectron microscopic observations.

Alzheimer's neurofibrillary tangles (NFT) and paired helical filaments (PHF) were found in the pheochromocytoma cells of the adrenal gland removed from a 54-year-old female. By electron microscopy they were identical to those found in the brains affected by dementia of Alzheimer type. In the tumor cells, most of the PHF were found dispersed loosely in the cytoplasm, while typical NFT were infrequent. By immunoelectron microscopy using peroxidase-antiperoxidase method, both NFT and dispersed PHF were stained positively with a polyclonal antiserum to human tau protein. This is the first observation of NFT and PHF in paraneuronal tumor cells. The patient has no obvious Alzheimer's disease.

Adrenal Gland Neoplasms↗
PubMed1990

Ultrastructural study of the human pineal gland in aged patients including a centenarian.

An ultrastructural study of human pineal glands obtained at autopsy from 7 patients older than 70 years was conducted in order to clarify the functional anatomy of the pineal in the aged. By light microscopy, the pineal glands from aged patients were parenchymatous and almost indistinguishable from those of younger controls. Electron microscopy of the pineal parenchymal cells revealed deep nuclear indentations, synaptic ribbons and ribbon fields, Golgi apparatus, lipofuscin granules and microtubular sheaves in all subjects, cilia with a 9 + 0 pattern in a few, and lamellated structures suggestive of the outer segment of photoreceptor cells very rarely. Microtubules were numerous in the cytoplasmic processes and bulbous endings. Fibrous astrocytes located between the pinealocytes showed long and thin cytoplasmic processes containing numerous glial filaments. Two types of nerve bouton were present in the pineal parenchyma, one of which contained clear vesicles forming synapse-like contacts with pinealocytes. There were no significant age-related changes in these features in a qualitative comparison with pineal glands from 5 adult patients younger than 70 years. These findings indicate that even in advanced age, the human pineal gland maintains some functions, such as intercellular communication and photoreception, in common with the pineal in lower vertebrates.

Adult↗
PubMed1990

Therapeutic drug monitoring services at Kyushu University Hospital in Japan.

Quantitative evaluation of the therapeutic drug monitoring services (TDMS) provided in Kyushu University Hospital from August 1981 to April 1989 was performed. Since 1982, the annual number of assay requests was about 4300-4400, but the annual number of clinical pharmacokinetic consultation services (CPCS) showed a tendency to increase. Antiepileptics were the drugs for which CPCS were most often performed (26.3 percent of the population given drugs for which TDMS was available); digoxin, lithium, and theophylline followed. Preparation of one consultation required 1.5-2.5 hours. Our TDMS team consists of eight members. In 1988, the average time per week spent for CPCS and TDMS was 8.2 and 11.3 hours per member, respectively. Thus, the number of pharmacists performing CPCS and TDMS was 1.2 and 1.7 full-time equivalents, respectively.

Drug Information Services↗
PubMed1989

Sensitive determination of ambenonium chloride in serum from patients with myasthenia gravis using ion-exchange resin extraction and reversed-phase ion-pair chromatography.

An effective and selective procedure for the extraction of ambenonium chloride (AMBC) from serum using a weak cation-exchange extraction cartridge has been developed. The solid-phase extraction procedure permitted the extraction of AMBC from serum without adhesion to materials such as the containers. A 200-microliter volume of the eluate could be directly injected on to a reversed-phase ion-pair high-performance liquid chromatographic column. The recovery was in the range 97-100%. The limit of detection for AMBC was 0.5 ng/ml in serum (signal-to-noise ratio = 3). The method was used to determine the serum concentration of AMBC in patients with myasthenia gravis. The method would be useful for monitoring AMBC in serum in order to study its pharmacokinetic behaviour in patients under oral administration therapy.

Adult↗
PubMed1989

Clinical and pathological features of acute interstitial pancreatitis in the aged.

Histological examination of the pancreas disclosed acute diffuse interstitial pancreatitis in nine cases (0.62%) out of 1457 autopsies performed in 3 yr at two general hospitals in Tokyo. In this series, there were 11 cases of necrotizing or hemorrhagic pancreatitis. In addition to diffuse phlegmonous inflammation, acute interstitial pancreatitis was characterized by rupture of the ducts and ductules associated with profuse intraluminal exudation of polymorphonuclear leukocytes and protein plugs formation. There was scarce parenchymal or fat necrosis. The interstitial type may represent characteristics of acute pancreatitis in the aged. In all nine cases, there were few clinical signs suggestive of acute pancreatitis, except for shock, that developed rapidly. Duration of the disease was rather short. Diagnosis of acute pancreatitis was not made before death. In five patients, acute pancreatitis was terminally superimposed on other serious ailments. But in the other four cases, acute pancreatitis was disclosed as the primary disease at autopsy. Although there was only one case that had a possibility of being secondary to biliary tract infection, ascending bacterial infection and impaired secretion by atrophic parenchyma seemed to be involved in its pathogenesis.

Acute Disease↗
PubMed1989

Age-associated ultrastructural changes in the aortic intima of rats with diet-induced hypercholesterolemia.

The ultrastructure of the aortic intima and serum lipid levels in Fischer 344 rats were examined at the ages of 12, 18 and 24 months after feeding the animals an atherogenic diet (2% cholesterol, 0.25% sodium cholate, 5% beef fat) for 6 months. Structural changes in the intima were noticeable only at the age of 24 months. In control rats, the endothelial cells were irregular in shape and each had a well-developed Golgi complex and a few lipid droplets. Simultaneously, reticular, basal lamina-like material and electron-dense granules of extracellular liposomes accumulated in the subendothelium. In fat-fed rats, these structural changes were more conspicuous in association with hypercholesterolemia, and numerous monocytes with lipid droplets were attached to the endothelium, occasionally invading into the subendothelium. Slight foam cell lesions were evident in the intima. The finding that older rats were more susceptible to the atherogenic diet suggests that atherogenesis in the rat is promoted by intrinsic age-associated changes in the aortic intima.

Aging↗
PubMed1989

Subchronic feeding studies with nivalenol in C57BL/6 mice.

Groups of ten C57BL/6CrSlc SPF mice of each sex were fed diets containing 0, 6, 12 or 30 ppm nivalenol for 4 or 12 wk. Body-weight gains of males and females were depressed, dose-dependently in the case of males. Feed consumption was also depressed. Treatment-related changes in liver, kidney, spleen and thymus weights were seen in some groups but showed no clear trends. No gross or histopathological lesions were seen in the organs examined but treated groups had considerably less fatty tissue at autopsy than did controls. There was a dose-dependent increase in serum alkaline phosphatase activity. Other serum parameters showed scattered significantly altered value but no clear trends, except for serum GOT values for males fed 12 and 30 ppm for 12 wk; these showed a statistically significant dose-related increase, but were within the normal range and were not considered to indicate hepatotoxicity.

Animals↗
PubMed1989

Chronic toxicity of nivalenol in female mice: a 2-year feeding study with Fusarium nivale Fn 2B-moulded rice.

Groups of 42 7-wk-old female C57BL/6CrSlc SPF mice were fed diets containing 0, 6, 12 and 30 ppm nivalenol (NIV) for 2 years. Body-weight gain was reduced in all treated groups of animals and feed efficiency was reduced, significantly so, in the high-dose group. The absolute weights of the liver in the 30-ppm group, and of the kidneys in the 12- and 30-ppm groups were significantly reduced, compared with those of the controls. When expressed relative to brain weight there was a reduction in the kidney weight of the 12-ppm NIV group only. Some leucopenia was seen in the treated mice, particularly in the 30-ppm group, although this was not statistically significant, and there were dose-dependent increases in the serum concentrations of alkaline phosphatase and non-esterified fatty acids. No tumours attributable to NIV were found in any of the experimental groups. Naturally occurring tumours, mostly lymphomas, were of similar incidence in all groups, but developed later and appeared to grow more slowly in the mice of the 30-ppm group than in those of other groups. The incidence of amyloidosis, particularly in the small intestine, was low in the two higher dose groups compared with that in the control group. The mortality rate of the 30-ppm NIV group was lower than that of the control group and this may be partly due to the lower tumour incidence in the earlier period and partly due to the lower incidence of amyloidosis.

Amyloidosis↗
PubMed1989

Stenotic lesions and length of the left main coronary artery in the aged.

To evaluate lesions of the left main coronary artery (LM) in the aged, a pathologic study was performed on a total of 972 consecutive autopsy cases over 60 years of age. The study population consisted of 503 men and 469 women with an average age at death of 79.0 years. In this study the degree of narrowing and length of the LM were evaluated in all cases (T), and the 141 cases with normal hearts (N) were compared with the 202 cases with myocardial infarction (MI). The following results were obtained: (1) the average coronary stenotic index (CSI) was 9.1/15 in T, 5.8/15 in N and 11.2/15 in MI (N less than MI, p less than 0.001), (2) the grade of narrowing in the LM (LMG), when 100% obstruction of the LM is counted as 5, was 1.8 +/- 0.9 in T, 1.3 +/- 0.6 in N and 2.3 +/- 1.1 in MI (N less than MI, p less than 0.001). Cases showing more than 75% narrowing of the LM were found in 58 (6%), of which 35 cases belonged to MI, but development of MI directly due to lesions in the LM was found in only 9 patients (4.5% among MI), (3) the average length of the LM (LML) was 9.4 +/- 4.4 mm in T, 9.0 +/- 4.2 mm in N and 9.3 +/- 3.8 mm in MI (N vs MI; n.s.). Cases presenting left coronary artery dominance (n = 82) or a balanced type (n = 159) showed shorter LML than those with right coronary artery dominance (n = 729) (8.5 +/- 4.0 mm, 8.8 +/- 4.6 mm and 9.7 +/- 4.4 mm, respectively, p less than 0.05), (4) in T there was a correlation between the LMG and CSI, but not between the LML and CSI. In conclusion, lesions of the LM in the aged were generally mild and the LMG showed a positive correlation with CSI and the narrowing of each coronary branch, while no relationship was noted between the LML and CSI.

Aged↗
PubMed1988

Incidence, sites of origin, and immunohistochemical and histochemical characteristics of atypical epithelium and minute carcinoma of the papilla of Vater.

To elucidate the relationship between atypical epithelial growth and cancer of the papilla of Vater, histologic, histochemical, and immunohistochemical observations were made of the autopsy cases of mainly elderly people. The atypical grades of the epithelium were histologically classified into five groups: normal epithelium, Group 1; mild atypism, nonmalignant, Group 2; moderate atypism, borderline, Group 3; severe atypism, possibly malignant, Group 4; and apparent carcinoma, Group 5. The incidences of each group in 576 autopsy cases were 65.8%, 30.0%, 3.1%, 0.9%, and 0.2, respectively. The atypical epithelia were observed with the highest incidence in the common pancreaticobiliary channel. The immunohistochemical stainings for cancer-associated antigens (carcinoembryonic antigen [CEA] and carbohydrate antigen 19-9 [CA 19-9]) and histochemical stainings for mucin (periodic acid-Schiff [PAS] and alcian blue [AB], pH 2.5 and pH 1.0) revealed that most of the Group 1 and 2 epithelia were negative for CEA and positive for AB, pH 2.5. Group 3 and 4 epithelia were negative for both CEA and AB, and Group 5 epithelia were positive for CEA but negative for AB (chi-square test, P less than 0.01). A combination of CEA and AB pH 2.5 stainings may be helpful in the histologic diagnosis of normal epithelium to mild atypism, moderate to severe atypism, and carcinoma. The study on the relationships between atypical epithelia showed that some carcinomas of the papilla of Vater may arise from atypical epithelia.

Aged↗
PubMed1988

The acute and chronic toxicities of nivalenol in mice.

In an attempt to ascertain precisely the toxic effects of nivalenol (NIV), we conducted the determination of LD50 values, and interim kills during the carcinogenic study in mice. LD50 values (mg/kg) of NIV in 6-week-old male ddY mice were determined as 38.9 (po), 7.4 (ip), 7.2 (sc), and 7.3 (iv). Seven-week-old female C57BL/6CrSlc SPF mice were fed diets containing 0, 6, 12, and 30 ppm (mg/kg) NIV over 1 year, and were assessed for effects on body weight gain, feed efficiency, terminal organ weights, hematology, and histopathology. The rates of body weight gain and feed efficiency showed a good dose-dependent correlation in all experimental periods. Gross and histopathological evaluation of the liver, thymus, spleen, kidneys, stomach, adrenal glands, pituitary gland, ovaries, sternum, bone marrow, lymph node, brain, and small intestines with or without Peyer's patch portion from control and all NIV-exposed mice revealed that these tissues were normal in appearance and in histopathological structure. Also, no changes were observed in the ultrastructural studies on the bone marrow. Dietary NIV did, however, cause dose-dependent decreases of absolute organ weights (mg) and increases of relative organ weights (mg/g body weight) in the terminal organ weights recorded. A significant leukopenia was observed in the 30 ppm group at 6 months and in all NIV-treated groups at 1 year. No marked changes were observed in the other hematological parameters. These results indicated that 6 ppm or more of dietary NIV for 1 year showed a characteristic toxic effect of trichothecene mycotoxins in mice.

Animals↗
PubMed1988

Comparison of single-point phenytoin dosage prediction techniques.

To dose the anticonvulsant phenytoin (PHT) in a clinical situation is difficult because of the non-linear metabolism of the drug. Therefore many techniques have been advocated to aid dosage adjustments based on a single-point PHT concentration determined at steady-state (ss). We retrospectively investigated six methods in a population of 130 out-patients treated with PHT. The dose needed to achieve a desired PHT concentration at ss was calculated based on an observed ss dose-concentration pair using a Bayesian feedback method (B), the Richens and Dunlop nomogram (RD), the Rambeck nomogram (R), the Martin nomogram (M), a population clearance equation (PC), and the Wagner equation (W). The mean prediction error (ME), mean absolute error (MAE), and root mean squared error (RMSE) were separately calculated for each method, and served as a measure of prediction bias and precision. The MEs for B, RD, R, M, PC, and W, respectively, were -0.4, 1.2, 6.9, 3.4, -1.8, and 0.0 mg/day. The MAEs were 33.9, 38.5, 44.3, 50.4, 43.5, and 53.7 mg/day. The RMSEs were 43.7, 53.1, 65.2, 63.5, 56.0, and 68.2 mg/day. The MAE and RMSE showed lowest values for method B, followed by method RD. Therefore, we assume that method B is the most accurate in making routine PHT dosage adjustments.

Adolescent↗
PubMed1987

Pineal gland in old age; quantitative and qualitative morphological study of 168 human autopsy cases.

Age-related changes of human pineal gland were studied morphologically on 168 autopsy cases. Pineal weight in the formalin-fixed condition was 99 +/- 56 mg in males (n = 88, mean age 78 years) and 91 +/- 41 mg in females (n = 80, mean age 79 years), which showed no sexual difference (P = 0.290). There was no correlation between pineal weight and age of the patient (r = 0.0678, P = 0.191, n = 168). The pineal volume calculated as a spheroid was directly proportional to the weight (r = 0.904, n = 167, P = 0.000). A significant correlation existed between pineal weight and the degree of calcification (r = 0.231, P = 0.002, n = 156). The density of the pineals decreased with age (r = -0.164, P = 0.017, n = 167). The degree of calcification and cyst formation did not increase with age, but the grade of cyst formation was related to the pineal volume (P = 0.0002). Some pineals of the patients over 90 years old showed no calcification and appeared indistinguishable from the ones of the younger subjects. The weight and volume of the pineals of the patients with hypertension was appreciably greater than those of the non-hypertensive patients. These results indicate that human pineals do not necessarily degenerate progressively after involution.

Age Factors↗