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Biomedical subjects

H Ohtani

Publications and source records attributed to H Ohtani.

At least 127 records · Page 7Linked to original sources

[Hemostatic effect of a novel sheeted fibrin adhesive agent, TO-193, on experimental incision models].

TO-193 (TachoComb) is a new fibrin adhesive agent that consists of a collagen sheet coated with fibrin glue. We compared the hemostatic effect of TO-193 in several experimental models with Beriplast P as a fibrin adhesive agent, Avitene and Novacol as a microfibrillar collagen hemostat, and a sponge-like collagen sheet as the constitutional parts of TO-193. In the in vitro bleeding model in which blood leaks out through cotton cloth, the pressure of TO-193 when blood leakage was observed was higher than those of Beriplast P, Avitene, Novacol and the collagen sheet, indicating that TO-193 possessed a strong adhesive effect on the bleeding surface. On the kidney resection surface, TO-193 showed a more potent adhesive effect than those of Beriplast P and the collagen sheet, suggesting that TO-193 has a potent hemostatic effect. In the liver resection, TO-193 significantly reduced the bleeding volume compared with that of Novacol in normal rats. Furthermore, the bleeding volume of TO-193 was about half that of Beriplast P and equivalent to that of Novacol even in anticoagulant-treated rats. From these data, it is expected that TO-193 would be a valuable hemostatic agent for clinical use since TO-193 possesses a potent adhesive ability on the bleeding resection surface and would certainly stop bleeding in both patients with normal coagulation and those with a low blood coagulation condition.

Animals↗

Pathophysiologic significance of host reactions in human cancer tissue: desmoplasia and tumor immunity.

Invasive growth of malignant cells, particularly carcinoma cells, induces host reaction within and around tumor tissue. Representatives of them are desmoplasia, angiogenesis and immune reactions. Desmoplasia, a process of fibrosis, is induced by activation of fibroblasts with increased production of matrix proteins and matrix degrading enzymes. Angiogenesis is prerequisite for the growth of solid tumor. Inhibition of this is now a target of cancer therapy. The present author has proposed a concept that tumor vessels are composed of nutrient vessels and immune/inflammatory vessels. The latter is similar to venules in inflammatory lesions expressing the cell adhesion molecules to facilitate the transmigration of inflammatory cells to the tissue. In colon cancer, venules distributed along the invasive margin correspond to these vessels, which express E-, and P-selectins, and ICAM-1. These venules are considered to be an entry site of immune/inflammatory cells to cancer tissue. To further analyze immune mechanism, the present authors have confirmed that macrophages distributed along the invasive margin of colon cancer express costimulatory molecules B7.1/B7.2, which are required for the proliferation of T-cells. T-cells were co-localized with these cells. Clinicopathologic analysis confirmed that CD8+ T-cells distributed within cancer cell nest (intraepithelial) have the most significant impact on the patients' survival in colorectal cancer. These data suggest that various host reactions take place in the stroma of cancer tissue, which modulate the biologic behavior of cancer.

Fibrosis↗

[A sensitive enzyme immunoassay for the measurement of small quantities of erythrocyte-associated IgG in patients with systemic lupus erythematosus who had negative direct antiglobulin test].

To measure the amount of erythrocyte-associated IgG (EAIgG) molecules from 70 patients with systemic lupus erythematosus (SLE) who had negative direct antiglobulin test (DAT), we employed a sensitive enzyme-linked immunosorbent assay (ELISA) technique. Ninety-five percent of healthy individuals were less than 65 molecules of EAIgG per red cell (RBC). About 51 percent of these patients with SLE were positive (over 65 molecules of EAIgG per RBC) by this technique that showed more sensitive than the DAT. EAIgG levels of these patients were inversely proportional to RBC count (r = -0.369, p < 0.005), and EAIgG positive patients were recognized by 88 percent in patients group who were less than 4 x 10(6)/microliter RBC counts. These results suggest that even a few EAIgG, as of a DAT shows negative, are related to the catabolism of erythrocytes in patients with SLE. EAIgG determination value in this method calculated and converted with CRM 470 that is the IFCC international reference preparation for plasma protein.

Biomarkers↗

[Quantitation and heterogeneity of serum alpha 2-macroglobulin].

alpha 2-Macroglobulin (alpha 2M) is a major protease inhibitor in human plasma. In this study, serum alpha 2M was determined by means of immunoelectrophoresis (IEP), rocket immunoelectrophoresis (R-IEP), laser nephelometry (LN) and single radial immunodiffusion (SRID) in 133 subjects. The values obtained by these methods coincided well in most specimens, but some specimens showed disagreement. The sera of alpha 2M deficiency found by IEP were analyzed by the other methods. We found that R-IEP gave the results of alpha 2M deficiency most frequently while the other methods gave the results of normal alpha 2M level for some specimens. We studied on the presumption that the phenomenon is due to heterogeneity in molecular weight of alpha 2M. After alpha 2M was purified by affinity chromatography and gel filtration chromatography, we further employed gel-filtration on a high-performance liquid chromatography (HPLC) to isolate alpha 2M with different molecular size. Two peaks of immunoreactive alpha 2M were found by the gel-filtration HPLC. When we performed IEP for both portions, the first portion with higher molecular size showed larger rate of migration than the second portion. Serum alpha 2M quantitation with SRID is not appropriate because molecular weight influences on the determination by SRID. We conclude that R-IEP is best suitable for the detection of decrease of serum alpha 2M, although this method requires expertness of manipulation.

Adolescent↗

[Detection size dependence of field factor for narrow beam].

An absorbed dose in the narrow beam is calculated based on the depth dose distribution and a field factor. The field factor has to be measured with especially high accuracy because it is highly variable. The field factor was calculated when detection size was changed, by using Monte Carlo simulation, which had no energy dependency or geometrical error. Then the relation between field factor and detection size in the narrow beam was investigated. An absorbed dose in peak depth and reference depth according to detection size was calculated for each field size. Detection size dependency was recognized in the case of measuring a field factor, because the absorbed dose tended to decrease as detection size increased. The absorbed dose in the narrow beam has to be calculated within a change of +/- 2%. The change in peak depth according to detection size was eliminated, and then the relation between an absorbed dose at the ideal detection size of 0 mm phi by extrapolation and detection size which has a deference of 2% from it, were acquired. In addition, the maximum usable detection size was estimated in the case of measuring the field factor.

Models, Theoretical↗

[Plasma nicotinic acid levels in hemodialysis patients after the administration of niceritrol].

Lp(a) has recently begun to attract attention as a risk factor of atherosclerotic disease, especially of ischemic heart disease. The Lp(a) concentration in the serum was shown to be important for chronic hemodialysis patients who have high mortality due to cardiovascular disease. Nicotinic acid derivatives, which are recognized for their capacity to lower the serum Lp(a) concentration, are effective against a high Lp(a) concentration in hemodialysis patients. In this study, niceritrol which is a nicotinic acid derivative was tested on hemodialysis patients and healthy controls by investigating the serum nicotinic acid level. Serum nicotinic acid concentration was also measured by the severity of renal dysfunction of patients untreated by niceritrol. The blood nicotinic acid concentration in healthy controls (n = 4) was changed after 2 hrs by the administration of niceritrol from 9.8 +/- 1.4 ng/ml to 192.7 +/- 23.1 ng/ml then slowly decreased. Chronic hemodialysis patients who take niceritrol every day showed the highest nicotinic acid serum concentration (500-1,000 ng/ml) on the day without hemodialysis and the serum level decreased with dialysis for 4 hrs to 25-80%. There was no significant difference in the nicotinic acid level in the serum between healthy controls (n = 10), chronic glomerulonephritis patients (n = 7), chronic renal failure patients (n = 8) and chronic hemodialysis patients (n = 17). Lp(a) concentration in the serum, however, was increased with greater severity of renal dysfunction, The side effect was not observed in any cases administered niceritrol. These data suggest nicotinate derivatives are effective for hemodialysis patients. High nicotinic acid level in the serum after treatment with niceritrol was lowered by dialysis. It is plausible that the nicotinate level in patients without niceritrol treatment did not influence the Lp(a) concentration, because there was no increase in the nicotinate level of the serum even if the patients had renal dysfunction.

Arteriosclerosis↗

[Immunological background of plasma protein abnormalities--the relation between inflammation and malignant neoplasm].

Mechanisms causing negative findings of serum C-reactive protein (CRP) in inflammatory disorders and malignant neoplasms were investigated. Patients with advanced prostate cancer manifesting negative CRP and alpha 2M deficiency were found. This finding suggests that alpha 2M, a carrier protein of interleukin-6, mediates CRP synthesis by the liver. Mechanism of synthesis of acute phase proteins including CRP, SAA and others was shown to be different in response to inflammation, alpha 2M-dependence in alpha 2M deficiency, the production of CRP and SAA by human hepatoma cells (HepG2) and the processes on the transcriptional activation of acute phase protein genes. In cases of prostate cancer associated with serum alpha 2M deficiency metastasis to the bones was noted. This finding suggests that alpha 2M inhibits metastasis of prostate cancer. It was suggested that the alpha 2M deficiency develops from complex formation of alpha 2M with proteases including PSA and u-PA, and accelerated catabolism of the complex rather than suppressed production of alpha 2M.

Acute-Phase Proteins↗

[A role of clinical pathologists in Laboratory Information (Consulting) Center].

In the 21st Century, laboratory scientists must change their concepts and attitude in order to supply services and information of great value. The laboratory tests comprise an increasing volume, and medical workers frequently need consultation on these tests. Effective utilization of laboratory data are important aspects of evidence-based medicine, and will also contribute to the efficiency of hospital practice and management. Clinical Laboratory of Kitasato University Hospital opened the "Clinical Laboratory Information (Consulting) Center" in July 1995 to respond to the increasing demand for consultation. It has been supporting medical care and research. The Center is located on the second floor of the Clinical Laboratory building of Kitasato University Hospital, and is staffed by one medical technologist and a clinical pathologist specialized in laboratory medicine. The Center staff consults by telephone from 9 am to 5 pm on weekdays, and get inquiries after-work hours and during weekends either by e-mail or fax. The Center aims to improve medical care by providing accurate and up-to-date information on clinical laboratory tests and interpretations. The clinical pathologist of the Center attempts to advise physicians regarding appropriate tests for particular patients. This avoids the ordering of unnecessary tests, which benefits the patient, the physician, and the hospital. The clinical pathologist should keep abreast of new findings on a wide array of clinical laboratory tests. The clinical pathologist should respond immediately to requests and complaints, thereby always seeking to improve oneself and the Center. Our Center is the first clinical laboratory in Japan staffed by both a clinical pathologist and a medical technologist, and our Center could be a pilot study for a new service of hospital clinical laboratories.

Clinical Laboratory Information Systems↗

[The possibility of acute inflammatory reaction affects the development of pressure ulcers in bedridden elderly patients].

To test the hypothesis that acute inflammatory reaction associates with the development of pressure ulcers in bedridden elderly patients, 40 hospitalized elderly patients suffering from bacterial pneumonia, cerebrovascular disease, and femoral bone fracture were enrolled in this study. All of them were divided into two groups with pressure ulcers (group P; 17 patients) and without one (group N; 23 patients). The blood samples were taken from them within 5 days after the patients being bedridden. Although no significant difference exist in pressure ulcer risk factors (age, gender, Braden scale, underlying diseases, blood pressure, and heart rate) between the two groups, white blood cell, plasma C-reactive protein and fibrinogen in group P increased significantly as compared with those in group N. Besides number of platelets and maximum platelet aggregation rate were significantly higher in group P than in group N. Serum albumin and hemoglobin of both groups decreased after being bedridden, especially hemoglobin in group P was significantly lower than that in group N. While the concentration of serum IL-6 did not indicate a significant difference between both the groups, serum IL-1 beta increased significantly in group P. In conclusion, we suggested that acute inflammatory reaction releasing proinflammatory cytokines affected the development of pressure ulcer in bedridden elderly patients.

Aged↗

Optimization of excimer-forming two-probe nucleic acid hybridization method with pyrene as a fluorophore.

A previously presented homogeneous assay method, named the excimer-forming two-probe nucleic acid hybridization (ETPH) method, is based on specific excimer formation between two pyrenes attached at the neighboring terminals of two sequential probe oligonucleotides complementary to a single target. In this study, we investigated assay conditions and optimal molecular design of probes for intense excimer emission using a pyrenemethyliodoacetamide-introduced 16mer probe, a pyrene butanoic acid-introduced 16merprobe and a target 32mer. The length of the linker between the pyrene residue and the terminal sugar moiety remarkably influenced the quantum efficiency of excimer emission; the pair of linker arms of these two probes was optimal. The quantum efficiency was also dependent upon the concentrations of dimethylformamide and NaCl added to the assay solution. Spectroscopic measurements and T m analysis showed that an optimal configuration of the two pyrene residues for intense excimer emission might be affected by pyrene-pyrene interaction, pyrene-duplex interaction (intercalation/stacking) and solvent conditions as a whole. We then demonstrated the practicality of the ETPH method with the optimal hybridization conditions thus attained by determining that the concentration of 16S rRNA in extracts from Vibrio mimicus ATCC 33655 cells in exponential growth phase is 18 500 16S rRNA molecules/cell on average.

Absorption↗

Correlation analysis between fatty acid compositions of zooplankter individuals, fed on different phytoplankton species by means of pyrolysis-gas chromatography combined with on-line methylation.

Pyrolysis-gas chromatography (Py-GC) combined with on-line methylation was applied to a correlation analysis between the distributions of fatty acid components in the lipids of zooplankter individuals and those of ingested algae using principal component analysis (PCA). Py-GC in the presence of organic alkali, tetramethylammonium hydroxide (TMAH), was used to estimate the apparent distributions of fatty acid components contained in a single individual zooplankter weighing several tens of micrograms and a small sample size of ingested algae samples in the order of 10 microg. The observed fatty acid compositions were used as a database for the PCA in order to discriminate the zooplankton and ingested algae samples. The result obtained indicated that the fatty acid compositions of zooplankton individuals used in this work were significantly reflected in those of their ingested food in spite of some contribution from isomerization and/or elongation of fatty acid components during digestion of the ingested algae phytoplankton in living zooplankters.

Animals↗

CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer.

The pathophysiological significance of tumor infiltrating lymphocytes remains controversial. To clarify their role, we performed clinicopathological analysis of CD8+ T cells in 131 cases of human colorectal cancer. CD8+ T cells were classified into three groups by their localization: (a) those infiltrated within cancer cell nests; (b) those distributed in the cancer stroma; and (c) those present along the invasive margin (tumor-host interface). Of these, CD8+ T cells within cancer cell nests were most significantly associated with a better survival of patients by both mono- and multivariate analyses. The impact on survival was similar to that of Dukes' staging. Granzyme B+ cytoplasmic granules were detected in lymphocytes within cancer cell nests, confirming their activated, cytotoxic phenotype. CD8 and Ki-67 double immunohistochemistry confirmed higher proliferative activity of CD8+ T cells within cancer cell nests. Our data suggested that human colorectal cancer tissue was infiltrated by various numbers of T cells that had cytotoxic phenotype, contributing to a better survival of patients. This infiltration of colorectal cancer cell nests by CD8+ T cells could be a novel prognostic factor.

Analysis of Variance↗

Procollagen-positive fibroblasts predominantly express fibrogenic growth factors and their receptors in human encapsulation process against foreign body.

This paper addresses the in situ expression of transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), and their receptors in the encapsulation process against a foreign body, using 20 cases of the titanium miniplate as a model of the foreign body, used clinically to fix a fractured mandible. Fibrous tissue formed during the encapsulation process was composed of scar-like and fibrogenic layers, with the former directly facing the foreign body. By immunohistochemistry using pre-fixed frozen sections, only the fibrogenic layer was characterized by expression of type I procollagen (PC-I). Spindle-shaped mesenchymal cells in the fibrogenic layer expressed TGF-beta isoforms and receptors, PDGF isoforms, and PDGF beta-receptor. In contrast, the scar-like layer had few such cells. In both layers, spindle-shaped cells did not express Ki-67 in their nuclei. Double immunofluorescence microscopy for cell identification revealed that most PC-I-positive fibroblasts expressed both isoforms and receptors of TGF-beta and PDGF in the fibrogenic layer, while in contrast, they were expressed by only a small number of CD68-positive macrophages. These results suggest that in the maintenance stage of the human encapsulation process against a foreign body, both TGF-beta and PDGF function cooperatively via their receptors in the fibrogenic layer, with such stimuli markedly diminished in the scar-like layer.

Adolescent↗

Effects of hypokalaemia on arrhythmogenic risk of quinidine in rats.

Plasma potassium concentration plays an important role in the induction of arrhythmia and is closely related to the arrhythmogenicity of various drugs. We quantitatively analyzed the influence of plasma potassium concentration on QT intervals before drug administration and on drug-induced QT prolongation, to estimate the risk of drug-induced arrhythmia under hypokalaemic conditions. The hypokalaemic models were produced by intraperitoneal administration of furosemide and hydrochlorothiazide in male Sprague-Dawley rats. The relationship between the changes in QT intervals and time profiles of plasma quinidine (QND) concentration were analyzed during constant intravenous infusion of QND (10 or 30 mg/kg/h) and post infusion in normal and hypokalaemic rats. The plasma QND concentration reached the therapeutic range (3-7 microg/ml) at the high infusion rate (30 mg/kg/h). No pharmacokinetic differences between normal and hypokalaemic rats were observed. QND induced QT prolongation in parallel with the plasma concentration without hysteresis. Although the potency of QND for QT prolongation was not affected by hypokalaemia, the QT intervals before drug administration were significantly prolonged in hypokalaemic rats (65.90 +/- 1.40 vs 56.60 +/- 0.748 msec, mean +/- SEM, p < 0.0001). Thus, the prolongation of QT intervals before drug administration may act as a risk factor of arrhythmia under hypokalaemic conditions.

Animals↗

Remission of the nephrotic syndrome in a patient with renal amyloidosis due to rheumatoid arthritis treated with prednisolone and methotrexate.

A 46-year-old woman developed nephrotic syndrome secondary to rheumatoid arthritis (RA). A renal biopsy showed deposition of amyloid fibrils in the subendothelial space of the glomerular capillary walls. After treatment with prednisolone (PSL, 40 mg/day), the levels of C-reactive protein (CRP) and serum amyloid A decreased to within normal limits for 2 weeks. However, the nephrotic syndrome persisted for 6 months after the therapy. To maintain the suppression of disease activity and to reduce PSL, methotrexate (5 mg/week) was added. The nephrotic syndrome resolved gradually, and the level of serum albumin returned to normal. Although renal prognosis of patients with nephrotic syndrome due to amyloidosis caused by RA has been considered poor, adequate and long-term treatment of RA with antiinflammatory drugs, including PSL and methotrexate, is useful for patients with secondary amyloidosis complicated by RA.

Amyloidosis↗