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Biomedical subjects

K Ohtsubo

Publications and source records attributed to K Ohtsubo.

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

Association between pulmonary microthromboembolism and coagulation variables in hypercoagulable states: an autopsy study.

OBJECTIVE: This autopsy study was carried out to investigate the relationship between the number of pulmonary microthromboemboli and coagulation tests in patients with coagulation abnormalities. METHODOLOGY: Fifty-one patients in whom coagulation studies were performed within 2 days prior to death were studied. The coagulation tests included platelet counts, prothrombin times expressed as International Normalized Ratios (INR), activated partial thromboplastin times, fibrinogen concentrations, plasma fibrinogen/fibrin fragment E antigen levels, and plasma D-dimer levels. For microscopic analysis, five tissue blocks of the lung were taken from each subject and the number of pulmonary microthromboemboli per 20 cm2 of tissue sections was calculated. RESULTS: Thirty-six of the 51 patients had pulmonary microthromboembolism. International Normalized Ratios were higher than 1.7 in 12 of 36 embolic and in two of 15 non-embolic patients (33.3% of sensitivity and 86.7% of specificity). There was no significant difference in D-dimer levels between the two groups. Multiple regression analysis identified that INR was significantly related to the number of microthromboemboli (P = 0.042). CONCLUSIONS: D-dimer levels appear to be inappropriate as a single screening test for disseminated intravascular coagulation (DIC) in critically ill patients because the levels in these subjects are elevated irrespective of the presence of microthromboemboli. Because of the high specificity, INR could be a specific marker for microthromboemboli. The significant association between the number of microthromboemboli and INR might indicate the importance of the extrinsic pathway in the initiation of DIC.

Aged↗
PubMed1999

Extensive involvement of the myocardium and the cardiac conduction system in a case of Wegener's granulomatosis.

A 61-year-old female who had shown Raynaud's phenomenon and articular swelling for 10 years, was admitted to hospital because of fever of unknown origin (FUO) and dry cough. She was diagnosed by skin biopsy to have a collagen disease or overlap syndrome. Anemia developed rapidly and FUO persisted, but blood culture was negative. Although indomethacin and prednisolone were administered for the progression of clinical signs and symptoms, severe dyspnea developed, resulting in bradycardia, followed by recurrent episodes of ventricular tachycardia. In spite of extensive treatment for her arrhythmia she died on the 9th hospital day. An autopsy revealed generalized Wegener's granulomatosis with extensive cardiac involvement. Necrotizing angitis and severe granulomatous inflammatory foci affected characteristically the common bundle of His and right bundle branch in addition to the ordinary myocardium.

Electrocardiography↗
PubMed1999

Detection of mutations of p53 tumor suppressor gene in pancreatic juice and its application to diagnosis of patients with pancreatic cancer: comparison with K-ras mutation.

Because of the difficulty in obtaining biopsy specimens from pancreatic cancer patients, K-ras mutation analysis in pancreatic juice has been used for specific diagnosis. But recently, false positives have been obtained with this method. To improve the genetic diagnosis of pancreatic cancer, detection of p53 gene mutation in pancreatic juice was studied. Pancreatic juice was sampled endoscopically. Single-strand conformation polymorphism analysis was used for p53 mutation analysis. Furthermore, K-ras mutations at codon 12 were also studied in the same pancreatic cancer patients. Of 26 cases of pancreatic cancer, p53 mutations were detected in 11 (42.3%). No mutations were seen in the cases with mucin-producing adenoma nor with chronic pancreatitis. K-ras mutations were detected in 84.0% of cases by RFLP analysis, which has high sensitivity, and in 65.3% by hybridization protection assay, which has high specificity. Using a combination assay with both genes, genetic abnormalities were detected in 92.0% by RFLP and 73.1% by hybridization protection assay including two cases in which p53 alone was positive by both methods. The specificity of p53 mutation for pancreatic cancer is very high. Therefore, simultaneous analysis of p53 and K-ras mutation is suggested to enhance the genetic diagnosis of pancreatic cancer.

Aged↗
PubMed1998

Pancreatic cancer associated with granulocyte-colony stimulating factor production confirmed by immunohistochemistry.

We report an 83-year-old man with pancreatic body cancer of 4.5 cm in diameter. Peripheral leukocyte count was 15,700/microl and the serum concentration of granulocyte-colony stimulating factor (G-CSF) was 123 pg/ml (normal, 6.0-21.9 pg/ml) on admission. Furthermore, not only K-ras codon 12 (GGT --> GAT) but also p53 at codon 247 (CGG --> CCG) mutations were identified in the pancreatic juice aspirated endoscopically. We performed chemotherapy with two courses of 5-fluorouracil, pirarubicin hydrochloride, and mitomycin-C, resulting in no beneficial effect. After the second course the patient developed interstitial pneumonia, probably caused by anticancer drugs, and died 4 months after the tumor was detected. In the autopsy tissue, the tumor macroscopically occupied the pancreas body and was 7 x 6 x 5 cm in size. Histopathologic diagnosis of the tumor was poorly differentiated adenosquamous carcinoma. Immunohistochemical staining of the autopsy tissue showed that pancreatic cancer cells were positive for G-CSF. This is the first case report of G-CSF-positive pancreatic cancer confirmed by immunohistochemistry.

Aged↗
PubMed1998

Rheological properties and lipid oxidation of rice decontaminated with low-energy electrons.

Microbial load and quality of rice grains which were exposed to electrons at different acceleration voltages of 170 to 200 kV were examined to evaluate the efficacy of decontaminating rice with low-energy electrons. Electrons at any acceleration voltage between 170 and 200 kV reduced microbial loads of brown rice grains to levels lower than 10 colony-forming units (CFU)/g. Higher acceleration voltages resulted in a lower viscosity and a higher thiobarbituric acid value (TBA). Milling at a yield of 90 or 88% after electron treatment made the viscosity and TBA of rice treated with electrons at 170 kV almost the same as untreated rice. Low and high compression analyses of rice grains which were exposed to electrons at 170 to 180 kV and milled at a yield of 90% followed by cooking showed almost the same hardness and stickiness as untreated grains which were milled at 90%. The results indicate that milling at a yield of 90% or lower removes the portion of rice exposed to electrons at 170 kV and that treatment of brown rice with low-energy electrons enables the preparation of milled rice with extremely low levels of microbial load and little quality deterioration.

Decontamination↗
PubMed1998

Infrequent expression of p21 is related to altered p53 protein in pancreatic carcinoma.

This study is designed to investigate the expression of p21 and its relation to altered p53 protein in pancreatic carcinoma (PC). Immunohistochemical staining of formalin-fixed, paraffin-embedded tissue sections of PC was performed using a monoclonal antibody against p21 (187), with a parallel examination of altered p53 protein. The expression of p21 was only found in 12 of 58 (20.7%) PCs and, moreover, was mainly restricted to the well-differentiated ductal epithelium. Sixty-four % (37 of 58) of PCs showed positive p53 staining, and this change was significantly related to the absence of p21 expression (P < 0.01). In a subgroup, the proportion of the undetectable p21 expression and the expression of p53 were increased with increasing tumor grade but decreased with advancing clinical stage. The results of the present study suggest that the absence of p21 expression is very common in PCs and appears to relate to altered p53 protein. Moreover, the abnormalities involving the expression of p21 and p53 may play a more important role in the development than in the progression of this malignancy.

Adult↗
PubMed1997

Oxidative injury of synapse and alteration of antioxidative defense systems in rats, and its prevention by vitamin E.

In order to define whether active oxygen species actually induce oxidative damage to the nervous system, and how antioxidative defense systems are changed by oxidative stress, morphological and functional changes in the nervous system and antioxidant status were investigated. When rats were exposed to 100% oxygen in a chamber, many morphological changes, e.g. swollen astrocytes around vessels, deformed nuclei in nerve cells, pigmentation, swollen mitochondria, and abnormal accumulation of synaptic vesicles in swollen nerve terminals, were observed by electron microscopy. When synaptosomes isolated from oxygen-exposed rats were stimulated by KCl, acetylcholine release from the terminal was decreased more significantly than in synaptosomes from unexposed rats (P < 0.01). Synaptic plasma membrane fluidity decreased in response to oxygen exposure, and plasma membrane permeability to sucrose was increased significantly (P < 0.05). The cholesterol/phospholipid ratio of the plasma membranes was increased by oxidative stress and the content of unsaturated fatty acids, especially arachidonic acid and docosahexaenoic acid, decreased. The levels of thiobarbituric-acid-reactive substances in the plasma membranes of oxygen-exposed rats were significantly higher than in unexposed rats (P < 0.01). These results suggest that free radicals derived from oxygen may attack nerve terminals and peroxidize the plasma membrane. It was found that in response to the oxidative stress, the status of the defense system in synapse, i.e. the concentration of vitamin E, activities of superoxide dismutase and glutathione peroxidase changed, and that many of the changes observed were reduced remarkably by the intraperitoneal administration of vitamin E prior to stress. Data support the idea that vitamin E contributes to the protection against nerve dysfunction caused by oxidative stress.

Acetylcholine↗
PubMed1997

Systemic sclerosis associated with diabetes insipidus.

A rare case of systemic sclerosis that preceded the development of diabetes insipidus is reported. This 25-year-old man presented with Raynaud's phenomenon and ulceration of the tip of the right thumb. The diagnosis of systemic sclerosis was based on findings of proximal scleroderma, sclerodactyly, serological abnormalities, and skin abnormalities verified histologically. Partial central diabetes insipidus was later diagnosed after the sudden appearance of polyuria and polydipsia. Coexistence of systemic sclerosis with diabetes insipidus suggests that diabetes insipidus in this patient might have occurred via an autoimmune mechanism.

Adult↗
PubMed1997

Frequent loss of p16 expression and its correlation with clinicopathological parameters in pancreatic carcinoma.

Expression of the p16 gene product in human primary pancreatic carcinoma (PC) was investigated in paraffin-embedded tissue using a monoclonal antibody against p16 protein, clone G175-405, by means of immunohistochemistry, and the correlation of results with various clinicopathological parameters was evaluated. All six cases of normal pancreas and all but 1 of 20 cases of chronic pancreatitis expressed p16 protein, whereas 37.5% (3 of 8) of cystadenomas and 41. 9% (26 of 62) of PCs lost p16 expression. There was a significant difference between chronic pancreatitis and PC for frequency of the loss of p16 expression (P < 0.01). Moreover, loss of p16 expression in pancreatic malignancy was significantly associated with histological grade (G1 versus G2 and G3, P < 0.01) but not with sex, age, clinical stage, tumor location, or resectability. The survival period was shorter and metastasis is more likely in those cases that did not show p16 expression than those that did.

Adenocarcinoma↗
PubMed1996

Exposure to dimethylarsinic acid, a main metabolite of inorganic arsenics, strongly promotes tumorigenesis initiated by 4-nitroquinoline 1-oxide in the lungs of mice.

The effect of dimethylarsenics on the pulmonary tumorigenesis initiated by 4-nitroquinoline 1-oxide (4NQO) in mice was examined. The exposure of mice to dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics in mammals, resulted in not only promotion but also progression of the tumorigenic process in the lungs of mice administered 4NQO. Furthermore, dimethylarsenics influenced the differentiation process in lung tumorigenesis by 4NQO. These results may pave the way for the elucidation of lung carcinogenesis caused by arsenics.

4-Nitroquinoline-1-oxide↗
PubMed1995

Effect of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) enantiomers, major metabolites of phenytoin, on the occurrence of chronic-gingival hyperplasia: in vivo and in vitro study.

The purpose of this study was to assess the possible role of the (R)- and (S)- enantiomers of the phenytoin metabolite p-HPPH in the pathogenesis of gingival hyperplasia (GH). About 98% of circulating p-HPPH is in the (S)-form. There were significant differences between patients with and without GH in (R)-p-HPPH level (0.055 vs 0.042 microgram.ml-1), both enantiomer/racemate level ratios, and R/S enantiomeric ratio (0.0313 vs 0.0232); an increase in serum (R)-p-HPPH level was observed in patients with GH. In separate experiments, the effect of p-HPPH enantiomers on the proliferation of the normal human dermal fibroblast was studied. The in vitro study showed that (R)-p-HPPH selectively stimulated fibroblast growth. The results suggest that the least abundant metabolite, (R)-p-HPPH, is the most toxic with respect to gingival hyperplasia.

Adult↗
PubMed1995

Pharmacokinetic study of valproic acid sustained-release preparation in patients undergoing brain surgery.

Pharmacokinetics of valproic acid sustained-release preparation (VPA-SR) were studied in nine patients undergoing surgery for brain tumor. Total (t) and free (f) serum concentrations were analyzed in samples drawn during the day of brain surgery and compared with levels from a postoperative day. The area under the curve (AUCt) and clearance (CLt) of the total concentration did not differ on these occasions. In contrast, statistically significant differences were observed in AUCf and CLf between the two occasions; increased AUCf and decreased CLf were observed on the day of surgery. A significant relation was found between the average free fraction (AUCf/AUCt on operation day per AUCf/AUCt on postoperative day) and estimated blood loss during operation (r = 0.82; p < 0.001). In addition, a significant relation was found between simple free fraction and the intraoperative albumin level in serum (r = -0.68; p < 0.001). These findings indicate that the increased VPA free concentration is due to low serum albumin level secondary to blood loss and that there has been a decrease in intrinsic clearance during operation.

Adolescent↗
PubMed1995

Incidence of pulmonary thromboembolism, infarction and haemorrhage in disseminated intravascular coagulation: a necroscopic analysis.

BACKGROUND: The pathological features of the lung in disseminated intravascular coagulation (DIC) have not been established. This study was carried out on lungs taken at necropsy to examine the incidence and extent of thromboembolism, infarction, and haemorrhage. METHODS: The subjects were 87 patients whose illnesses were complicated by DIC and 64 patients who showed no abnormalities of blood coagulation in their terminal illness. The lungs were fixed by intrabronchial infusion of 10% formalin, cut into 5 mm thick slices, and each cut surface was carefully examined for macroscopic thromboembolism, infarction, and haemorrhage. Five tissue blocks per case were taken for quantitative analysis of microscopic thromboembolism. RESULTS: In the control group macroscopic thromboembolism was identified in 20 cases (31.3%), infarction in one, and haemorrhage also in one. Moreover, fibrin thrombosis was seen in 13 cases (20.3%) and microthromboembolism in 24 (37.5%). Of the 87 patients with DIC, thromboembolism was found in 51 cases (58.6%), infarction in six, haemorrhage in 14, microscopic fibrin thrombosis in 43 (49.4%), and microthromboembolism in 45 (51.7%). Macroscopic thromboembolism, haemorrhage, and fibrin thrombosis were found more often in the patients with DIC. CONCLUSIONS: In addition to fibrin thrombosis, macroscopic thromboembolism and haemorrhage were the main pathological findings in the lungs of patients dying with DIC. The frequency of pulmonary infarction increased in proportion to the frequency of thromboembolism.

Aged↗
PubMed1995

Colocalization of vascular endothelial growth factor (vascular permeability factor) and insulin in pancreatic islet cells.

Previously, we found that the islet of pancreas stained with a antibody against the vascular permeability factor (VPF; also known as vascular endothelial growth factor, VEGF) protein. To determine how common this reaction was and whether it was a specific reaction for the islet, we examined its expression and specific cellular localization. Two different antibodies directed against VPF/VEGF peptide revealed an intense reaction for beta-cells in the human islets of Langerhans, and several human beta-cell tumors (insulinomas), but no reaction, were detectable in the vascular endothelium. In the fetal pancreas (second and third trimesters), the VPF/VEGF peptide was detected in immature islets. Northern blot analysis of cell lines derived from rodent insulinomas revealed expression of VPF/VEGF messenger ribonucleic acid. Western blot analysis of conditioned medium from one of these cell lines showed the presence of the released VPF/VEGF protein. These findings indicate that beta-cells have a specific role other than endocrine function in the pancreas. VPF/VEGF in beta-cells may be involved in the maintenance and control of permeability within the islet capillary system.

Adult↗
PubMed1995

[Histological evaluation of bronchial tissue from elderly individuals with bronchial asthma].

We studied morphologic and morphometric characteristics of the bronchial walls in lungs obtained at autopsy form elderly patients who had had bronchial asthma. Thirteen patients (age at time of death 57 to 98 years; average, 81 years) were divided into three groups: AS, died of severe asthma attack (n = 4); AC, admitted with asthma symptoms but died of other diseases (n = 6); and NA, died of other diseases and had had no asthma symptoms in the year before death (n = 3). Lungs from ten non-smokers with no history of bronchial asthma or other lung disorders were used as control. Transverse sections of segmental and subsegmental bronchi were prepared, and four quantities were analyzed: 1) the ratio of total bronchial gland area to total area of the bronchial wall (Yamanaka index), 2) the thickness of the basement membrane, 3) the thickness of the smooth muscle bundle, and 4) the ratio of luminal area to total area of the bronchial wall (bronchial dilation ratio). In the AS group, the Yamanaka index and the thickness of the smooth muscle bundles and of the basement membrane were significantly greater than those in the control group at both the segmental and subsegmental levels, with massive eosinophil infiltration into the bronchial walls. Furthermore the bronchial dilation ratio at the subsegmental level correlated closely with the Yamanaka index. Thickness of the smooth muscle bundle seemed to be most representative of the severity of asthma symptoms. In conclusion, morphometric findings of bronchial walls in elderly patients with asthma symptoms seem to be similar to those in their younger counterparts.

Age Factors↗