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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 541 records · Page 30Linked to original sources

Mechanisms of bronchoconstriction after allergen ingestion in sensitized guinea pigs.

We examined whether oral administration of allergen induced bronchoconstriction in sensitized guinea pigs and investigated the mechanisms of bronchoconstriction. The animals had been immunized intraperitoneally with a mixture of Ascaris suum extract and silica gel, and exposed to ozone. They were then challenged with an oral dose of A. suum extract (6 mg/kg), and respiratory resistance (Rrs) was measured up to 7 h. After oral administration of the allergen, an increase in Rrs was observed. The mean values at 1, 3, 5 and 7 h after oral allergen challenge were 150 +/- 21, 149 +/- 11, 151 +/- 12 and 134 +/- 10% of the baseline value, respectively. When saline instead of the allergen was orally administered, almost no significant increase in Rrs was observed up to 7 h. Moreover, in nonsensitized guinea pigs, oral administration of allergen produced no significant increase in Rrs for up to 7 h. When atropine was administered as an aerosol, the increase in Rrs induced by an oral allergen challenge was attenuated. Three of the five atropine-treated guinea pigs showed temporary increases in Rrs immediately after the oral allergen challenge. The mean values of Rrs in the atropine-treated animals challenged with oral allergen at 1, 3, 5 and 7 h were 106 +/- 3, 106 +/- 5, 115 +/- 5 and 102 +/- 4% of baseline value, respectively. In the animals which received oral allergen, the number of neutrophils in bronchoalveolar lavage fluid (BALF) significantly increased 2.0-fold (p < 0.05), while no significant increase in the number of eosinophils, macrophages, or lymphocytes in BALF was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Macrophage colony-stimulating factor regulates both activities of neutral and acidic cholesteryl ester hydrolases in human monocyte-derived macrophages.

Macrophage colony-stimulating factor (M-CSF) regulates cholesterol metabolism in vivo and in vitro. We studied the effects of M-CSF on enzyme activities of acidic cholesteryl ester (CE) hydrolase, neutral CE hydrolase, and acyl-coenzyme A:cholesterol acyltransferase (ACAT), all of which are involved in cellular cholesterol metabolism in macrophages. During the differentiation of monocytes to macrophages, these enzyme activities were induced and further enhanced in response to M-CSF. M-CSF (100 ng/ml) enhanced acidic and neutral CE hydrolase and ACAT activities by 3.2-, 4-, and 2.3-fold, respectively, in the presence of acetyl LDL. The presence of acetyl LDL influenced these enzyme activities. ACAT and acidic CE hydrolase activities were increased and neutral CE hydrolase activity was decreased, indicating that these enzymes are regulated by intracellular cholesterol enrichment. M-CSF increased the ratios of acidic CE hydrolase to ACAT activity and of neutral CE hydrolase to ACAT activity. The results suggest that M-CSF enhances net hydrolysis of CE by stimulating the two CE hydrolases to a greater extent than ACAT, and M-CSF may reduce the rate of atherogenesis.

Base Sequence↗

beta 2-Microglobulin modified with advanced glycation end products is a major component of hemodialysis-associated amyloidosis.

beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis, a complication of long-term hemodialysis patients. Amyloid fibril proteins were isolated from connective tissues forming carpal tunnels in hemodialysis patients with carpal tunnel syndrome. Two-dimensional polyacrylamide gel electrophoresis and Western blotting demonstrated that most of the beta 2M forming amyloid fibrils exhibited a more acidic pI value than normal beta 2M. This acidic beta 2M was also found in a small fraction of beta 2M in sera and urine from these patients, whereas heterogeneity was not observed in healthy individuals. We purified acidic and normal beta 2M from the urine of long-term hemodialysis patients and compared their physicochemical and immunochemical properties. Acidic beta 2M, but not normal beta 2M, was brown in color and fluoresced, both of which are characteristics of advanced glycation end products (AGEs) of the Maillard reaction. Immunochemical studies showed that acidic beta 2M reacted with anti-AGE antibody and also with an antibody against an Amadori product, an early product of the Maillard reaction, but normal beta 2M did not react with either antibody. Incubating normal beta 2M with glucose in vitro resulted in a shift to a more acidic pI, generation of fluorescence, and immunoreactivity to the anti-AGE antibody. The beta 2M forming amyloid fibrils also reacted with anti-AGE antibody. These data provided evidence that AGE-modified beta 2M is a dominant constituent of the amyloid deposits in hemodialysis-associated amyloidosis.

Amyloidosis↗

Auto-growth inhibitory substance from the fresh-water cyanobacterium Phormidium tenue.

An extract of the cyanobacterium P. tenue showed a significant inhibitory effect on its own growth. Bioassay-directed fractionation has led to the identification of the auto-growth inhibitory substance as a mixture of fatty acids. Unsaturated fatty acids such as linoleic and linolenic acids appear to be predominantly responsible for the auto-growth inhibitory effect.

Cyanobacteria↗

Improved oral absorption of a poorly water-soluble drug, HO-221, by wet-bead milling producing particles in submicron region.

N-[[[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]amino]carbonyl]-2 -nitrobenzamide (HO-221) is being developed as an anticancer agent with a novel mode of action. HO-221 shows poor oral absorption and is only slightly soluble in water (0.055 micrograms/ml at 37 degrees C). In this study, it was shown that the reduction in particle size of HO-221 to the submicron region (0.453 microm, mean by volume) could be achieved by a wet milling in a decaglycerin monolaurate aqueous solution with small glass beads. The wet milling suspension obtained showed improved dissolution rate and oral absorption in rats. A solid dosage form could also be made from that suspension with addition of sucrose palmitate which prevented aggregation caused by the hydrophobic interaction. The solid dosage form thus obtained showed twice as much oral absorption in dogs as the preparation made by dry milling.

Animals↗

A novel mutation involved in the mitotic checkpoint in the fission yeast Schizosaccharomyces pombe.

The cps8 mutation which confers supersensitivity to a spindle poison, Isopropyl N-3-chlorophenyl carbamate (CIPC), in the fission yeast Schizosaccharomyces pombe was investigated. The cps8 mutant accumulated enlarged multinucleate cells in the stationary phase under normal growth conditions. The mutant was highly lethal at 36.5 degrees C in a fresh growth medium but not in a saline solution where the cell cycle ceases quickly. Lethality at high temperature was significantly suppressed by cdc1 or nda2 mutation which blocks nuclear division, but not by hydroxyurea treatment or cdc22 mutation which blocks DNA synthesis. A cdc10 cps8 double mutant remained lethal to high temperature, suggesting this double mutant to bypass the requirement for cdc10+ indispensable for the cell cycle start in a wild-type cell. After being transferred to a fresh medium at 36.5 degrees C, the multinucleate cells rapidly divided with aberrant nuclear segregation. Thus, cps8 mutation allows cells to undergo mitosis without DNA replication at the restrictive temperature. The cps8 gene was mapped on the left arm of chromosome II closely linked to but distinct from cdc2 locus.

Cell Cycle↗

A study on the values computed by dieticians and chemical analysis of fats, cholesterol, and P/S ratio in food.

Dieticians computed the fat and cholesterol contents of 11 foods that were commercially produced as ready-to-eat food from food component lists and obtained the P/S ratio (polysaturated/saturated fatty acids) from the fatty acid component list. Meanwhile the same foods were diluted and homogenized. The internal standard was combined with hepatadecanoic acid and tricaprin. The samples that had been extracted by the Folch method were analyzed for their lipid content (GC analysis using a HS-SS-10 columns for fatty acids and an OV-1 column for lipid and cholesterol). A significant positive correlation was noted between the results of dieticians' analysis and those obtained from a gas chromatographic analysis of lipid and cholesterol contents and the P/S ratio, proving that lipid analysis of food by dieticians is highly reliable. Therefore for diseases (such as hyperlipemia, arteriosclerosis, obesity, diabetes mellitus, fatty liver, and pancreatitis) in which dietary factors have a significant effect on their clinical course, dietary instructions on dietary fats based on an analysis by dieticians are considered to be effective.

Cholesterol↗

Apolipoprotein E polymorphism is associated with plasma cholesterol response in a 7-day hospitalization study for metabolic and dietary control in NIDDM.

OBJECTIVE: To investigate the effects of apolipoprotein E phenotype, which is an important genetic factor determining plasma cholesterol level, on plasma lipoprotein metabolism during a 7-day diet therapy of diabetes. RESEARCH DESIGN AND METHODS: Diet therapy was performed in 242 subjects with NIDDM. Plasma lipid levels and apolipoprotein A-I, B, and E levels on hospital days 2 and 9 were compared in three phenotype groups, epsilon 2 (E2/2, and E2/3), epsilon 3 (E3/3), and epsilon 4 (E3/4 and E4/4). RESULTS: No differences were observed in fasting blood glucose level, body mass index, age, duration of NIDDM, or medication among the three phenotype groups. Before starting the treatment, total plasma cholesterol did not vary by apolipoprotein E phenotype, although the mean plasma low-density lipoprotein cholesterol level in epsilon 4 patients was higher than in either epsilon 3 or epsilon 2 patients (epsilon 4, 145 +/- 42; epsilon 3, 131 +/- 34; epsilon 2, 128 +/- 36 mg/dl; P < 0.05). Changes in fasting blood glucose/body mass index after the 7-day treatment were not different among the apolipoprotein E phenotype groups, whereas the decrease in plasma cholesterol level after the treatment was significantly greater in epsilon 2 patients than in either epsilon 3 or epsilon 4 patients (epsilon 2, 10.3 +/- 14.2; epsilon 3, 6.1 +/- 11.0; epsilon 4, 3.8 +/- 9.6%; P < 0.05). CONCLUSIONS: Total plasma cholesterol response to in-hospital diet therapy varies by apolipoprotein E phenotypes, with subjects with apolipoprotein E2 showing the greatest response, whereas those with apolipoprotein E4 show the least. We suggest that subjects with apolipoprotein E4 should be controlled more strictly than other subjects from a viewpoint of reducing plasma cholesterol levels.

Alleles↗

[Immunohistochemical study of borderline thyroid lesions with special reference to relationships among nuclear features, type IV collagen and malignancy of follicular lesions].

It is very difficult to differentiate follicular adenoma from follicular carcinoma in thyroid follicular lesions. The authors investigated the biological behavior of these thyroid follicular lesions using immunohistochemical techniques. Specimens taken from normal thyroid, 2 cases; follicular adenoma, 9; atypical adenoma, 7; and follicular carcinoma, 8; were observed. Proliferating cell nuclear antigen (PCNA) is a marker of cellular proliferation. Nucleoli are also increased in number and move to the nuclear margin in cases of cellular proliferation. The PCNA labeling index was calculated by counting the number of PCNA-positive cells per 2,000 tumor cells. PCNA labeling indices were 0.025% in the normal thyroid, 1.41% in follicular adenoma, 5.73% in atypical adenoma, and 6.16% in follicular carcinoma, respectively. Nucleoli retaining rate of the tumor cells were 40.0% in follicular adenoma, 63.7% in atypical adenoma, and 71.8% in follicular carcinoma. Rates of nucleolus margination were 20.9% in follicular adenoma, 34.4% in atypical adenoma, and 36.0% in follicular carcinoma. Changes in the basement membrane were morphologically classified into three groups as follows; membrane structure almost preserved (group I), partial discontinuity (breaks) (group II), and widespread absence of membrane structure (group III), based on immunohistochemical investigation of Type IV collagen. Group I was demonstrated in 8 cases of follicular adenoma and one case of atypical adenoma. Group II was observed in one case of follicular adenoma, 3 cases of atypical adenoma and 3 cases of follicular carcinoma. In addition, group III was noted in 3 cases of atypical adenoma and 5 cases of follicular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Follicular↗

[The relation of CFQ (Cognitive Failures Questionnaire) to strategies of target search or focused attention].

Cognitive Failures Questionnaire devised by Broadbent, Cooper, Fitzgerald, and Parkes (1982) is a questionnaire which measures frequencies of failure behaviors in daily life. In this study, the relation between CFQ score and performance on visual attentional task was examined. Subjects were 20 female college students. In one task there was no information about target location, in other tasks signal stimulus was presented previously at the same location as target. The result indicates that, regardless of task condition, high CFQ score subjects tended to search the target, low score subjects focused their attention on the location where the target would be presented. These results agree with the notion of Broadbent, Broadbent, and Jones (1986).

Adult↗

[Leukocyte activity and occurrence of tissue injury by G-CSF].

G-CSF (granulocyte-colony stimulating factor) is one of the cytokines which increase and activate neutrophils. These effects have been confirmed by a lot of clinical studies. Although only few side effects have been reported so far, we saw a patient with hypertension, facial edema, and severe headache after G-CSF administration. We have measured the sticking strength of leukocytes to the walls of narrow pores in modified Nuclepore filtration method of Kikuchi, in various clinical situations, and we have denoted the pore filtration time as the rheological activity of leukocytes (RAL). In this study, we tried to measure RALs of patients after G-CSF administration (60-100 micrograms) and to compare them with those of non-treated normal individuals. We also checked serum levels of granulocyte elastase in the patients. In the static state (in which neutrophils were not stimulated), RALs of the patients were 8.0 +/- 1.5sec. [N = 8], and those of the controls were 3.8 +/- 1.6sec. [N = 21] (p < 0.001). In the activated state (in which neutrophils were stimulated by formyl-methionyl-leucyl-phenylalanine), PALs of patients were quite high, i.e. those of the patients and controls were 592 +/- 322sec. and 69 +/- 62sec., respectively (p < 0.001). In all cases given G-CSF, the serum levels of granulocyte elastase were above the normal range. In view of our results, we it is possible that highly activated leukocytes would injure tissue and then induce organ failure and several symptoms, as in this study.

Adult↗

Widespread expression of inositol 1,4,5-trisphosphate receptor type 1 gene (Insp3r1) in the mouse central nervous system.

The expression of inositol 1,4,5-trisphosphate receptor type 1 (InsP3R1) in the mouse central nervous system (CNS) was studied by in situ hybridization. The receptor mRNAs were widely localized throughout the CNS, predominantly in the olfactory tubercle, cerebral cortex, CA1 pyramidal cell layer of the hippocampus, caudate putamen, and cerebellar Purkinje cells, where phosphoinositide turnover is known to be stimulated by various neurotransmitter receptors. In the most abundantly expressing Purkinje cells, InsP3R1 mRNA appeared to be translocated to the distal dendrites, since a strong hybridization density was observed in the molecular layer of the cerebellum. InsP3R protein is known to form tetrameric receptor-channel complex. Our preliminary hybridization data using probes for three distinct InsP3R subtypes showed preferential expression of InsP3R1 in many parts of the CNS. The expression of other receptor subtypes (InsP3R2 and InsP3R3) is less efficient, suggesting that a homotetramer formed of InsP3R1 subtype may play a central part in InsP3/Ca2+ signalling in the neuronal function, whereas a homotetramer of other subtypes and a possible heterotetramer among subtypes may be involved in differential InsP3/Ca2+ signalling. The chromosomal localization of the gene coding for InsP3R1 was confirmed on chromosome 6 but was found to be genetically independent of the Lurcher (Lc) mutation.

Animals↗

Mutational analysis of human lipoprotein lipase by carboxy-terminal truncation.

We have previously reported a Trp382 (TGG)-->stop (TGA) mutation that causes familial lipoprotein lipase (LPL) deficiency. Expression study of the Trp382-->stop mutant showed that the truncated LPL was catalytically inactive with a marked reduction in the expressed mass. To investigate the minimal amino-terminal sequence of human LPL required for an active enzyme, a series of carboxy-terminal (C-terminal) truncated LPLs were expressed in vitro, and the enzyme activity, mass, and LPL mRNA levels were analyzed. The lipolytic activity showed a stepwise reduction between LPL-437 (Cys438-->stop; 68% of normal LPL activity in medium) and LPL-434 (Phe435-->stop; 3%). Without affecting LPL mRNA levels, LPL mass was reduced with the mutants not larger than LPL-437. In terms of specific activity, a significant difference was observed between LPL-436 (Lys437-->stop; 88% of that of normal LPL in medium) and LPL-435 (Val436-->stop; 22%), implying the importance of the role of Val436 in LPL action. Furthermore, our results unexpectedly showed that LPL-446 (Ser447-->stop), which is considered to be a common polymorphic form of LPL, exhibited higher activity than normal LPL (185% in medium). These results demonstrate that the C-terminal region of human LPL is closely associated with the expression of enzyme mass and catalytic activity.

Amino Acid Sequence↗

Effects of long-term, low-fat diet on plasma apo E in familial LCAT deficiency.

To study the metabolic abnormalities in familial lecithin-cholesterol acyltransferase (LCAT) deficiency, the effects of a long-term, low-fat diet and LCAT replacement therapy on plasma lipids and apolipoproteins were investigated in a patient with LCAT deficiency. The patient had elevated triglycerides (TG, 543.7 mg/dl) and phospholipids (PL, 350.3 mg/dl) and normal total cholesterol (TC, 206.9 mg/dl). Change to a low-fat diet reduced TC and TG by 20% and 75%, respectively. These reductions occurred mainly in the d < 1.006 fraction. At baseline, the patient had normal apolipoprotein B (apo B), low apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) and elevated apolipoprotein E (apo E). Long-term treatment with a low-fat diet increased plasma apoA-I and decreased apo E. However, urinary protein excretion did not change throughout the observed period. LCAT replacement with fresh frozen plasma (FFP) after the low-fat diet further reduced plasma apo E to the normal range. These results indicate that the elevated plasma apo E in LCAT deficiency was related not only to the lack of LCAT in the plasma, but also to fat intake. A low-fat diet may be effective in correcting lipid abnormalities. Moreover, plasma apo E may be a good indicator of the efficacy of diet therapy.

Apolipoproteins E↗

[A case of subtotal esophagectomy for esophageal basaloid carcinoma after mitral valve replacement].

We reported a rare case of subtotal esophagectomy for esophageal basaloid carcinoma after mitral valve replacement. Up to present, only this case had been printed in Japan. A 51-year-old male who had been performed MVR for mitral stenosis at the 44 complained of dysphagia. On esophageal X-ray and esophagoscopic findings showed round, irregular, and stenotic lesion (type-3) in the middle thoracic esophagus. We performed subtotal esophagectomy, esophagogastrostomy through the posterior mediastinal pathway and lymph node dissection (R2). Despite normal cardiac function before operation, the patient followed lung edema and perioperative measurement of Extra Vascular Lung Water Index (EVLWI) was stable within high level. On microscopic inspection, we revealed lots of basophilic basal cells mainly occupied submucosal layer coexisted with pseudoglandular formation and poorly differentiated squamous cell carcinoma. And the tumor cells strongly invaded into the lymph ducts and blood vessels. We need more detailed exploration for more cases about factors causing poor prognosis.

Carcinoma, Transitional Cell↗

Morphological changes of Candida albicans induced by BMY-28864, a highly water-soluble pradimicin derivative.

The time course of BMY-28864-dependent morphological changes in Candida albicans A9540 was studied by electron microscopy. Scanning electron microscopy revealed that BMY-28864 often induced cell surface deformations such as abnormal swelling and bulging around budding sites and bud scars. The cell membrane damage was visualized by freeze-fracturing technique as deep pit-like invaginations. Transmission electron microscopy with thin-sectioned specimens also demonstrated that BMY-28864 induced cell membrane invaginations together with cell membrane detachment from the cell wall, nuclear membrane fragmentation and mitochondrial aberration. Statistical sequence analysis of the prominent BMY-28864-dependent morphological changes of the yeast cells led to the conclusion that BMY-28864 first attacked the cell membrane and then caused disintegration of other intracytoplasmic organelles, resulting in the lethal effect.

Anthracyclines↗

[Usefulness of 201TlCl SPECT for evaluation of treatment effect of pancreatic cancer].

To assess the treatment effect of pancreatic cancer, thallium 201 chloride (201TlCl) SPECT was performed in three patients. All of the patients before and after treatment showed the same change between the tumor/liver uptake ratio of 201TlCl and the serum level of CA 19-9. In one of the patients, tumor shrinkage was not observed on CT. However, the uptake ratio decreased, accompanying with a reduced serum level of CA 19-9. These results indicate that 201TlCl SPECT is useful to evaluate therapeutic effect of pancreatic cancer.

Adult↗

[Changes of pulmonary perfusion in the lung area unaffected by embolism].

Observation of serial pulmonary scintigraphies after the treatment in the patients with pulmonary thromboembolism revealed altered perfusion in the lung area unaffected by embolism in 2 cases. Also, showed that recovered perfusion of the embolized lung area influenced the perfusion of contralateral embolic lung area in 1 patient. These findings were detected and confirmed by comparison of the serial scintigraphies mutually. These results indicate that the serial scintigraphy is useful not only for assessing perfusion recovery but also for detecting altered perfusion in the lung area unaffected by the embolism.

Aged↗