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Biomedical subjects

N Hirose

Publications and source records attributed to N Hirose.

At least 55 records · Page 3Linked to original sources
PubMed1997

Different effects of hypertension and hypercholesterolemia on the natural history of aortic atherosclerosis by the stage of intimal lesions.

To investigate the histopathologic modes of the effect of hypertension and hypercholesterolemia on atherosclerosis progression, a total of 573 male autopsied aortas, ranging from 0 to 97 years-old, were histomorphometrically compared by the status based on antemortem risk factors. Specimens were classified into four categories according to the criteria reported by the American Heart Association after histometric measurement at defined sites of the aortas. Intimal lesions progressed in the same fashion in all the risk factor groups examined; normal intima converted to fatty streak, preatheroma (characterized by microscopic extracellular lipid deposition) and then atheroma. This progression of intimal lesions correlated with age-related increases in intimal thickness independent of risk factors. Although the frequency of fatty streaks and the population of foam cells were greater in the hypercholesterolemics than in the non-risk patients, the frequencies of preatheroma and atheroma were not different between these two patient groups until patients reached the fifth decade. In contrast, the frequencies of preatheroma and atheroma were consistently greater in the hypertensives than in the other groups by the fifth decade. Hypertension was also related to intimal thickness in the younger groups. Our findings suggest that hypertension and hypercholesterolemia affect the progression of atherosclerosis differently by histopathologic stages.

Adolescent↗
PubMed1997

Bleomycin-induced lung disease in an animal model: correlation between computed tomography-determined abnormalities and lung function.

RATIONALE AND OBJECTIVES: The authors evaluated whether specific types of computed tomographic (CT) abnormalities could be correlated with physiologic impairment in animals with bleomycin-induced lung injury. METHODS: Lung injury was induced in 20 rabbits by means of intratracheal administration of bleomycin (3 U per kilogram of body weight), followed by 100% oxygen for 2 minutes. The animals underwent high-resolution CT scanning at 14 (n = 4), 28 (n = 6), or 56 (n = 10) days after injury. CT morphometry was used to determine the extent of abnormal lung. Physiologic evaluation was performed before injury and before scanning. RESULTS: The overall extent of abnormal lung and of parenchymal opacification on CT scans did not correlate with any physiologic variable. The extent of interstitial thickening correlated significantly with total lung capacity (r = -.783, P = .0005), airway pressure at maximal lung volume (r = .836, P = .0001), and alveolar-arterial oxygen gradient (r = .613, P = .004). CONCLUSION: CT findings of interstitial thickening are associated with impaired gas exchange and lung stiffness in rabbits.

Animals↗
PubMed1997

Correlation of clonal T cell expansion with disease activity in systemic lupus erythematosus.

It has been proposed that T cell activation may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). In order to examine this hypothesis, we assessed the whole degree of clonal accumulation of T cells using RT-PCR and subsequent single-strand conformation polymorphism (SSCP) analysis. The analysis of the beta chain of the TCR revealed little clonotypic T cell expansion in the peripheral blood of lupus patients in remission, whereas in patients with active disease many dominant T cell clonal expansions without any distinct V beta bias were observed. The alteration in the number of T cell clones correlated well with disease activities, since these T cell expansions decreased as patients had improved. Furthermore, similar but more intense accumulations of T cell clones were found in pleural and pericardial effusions of patients with lupus serositis. Some of these identical expanded clonotypes were observed irrespective of the lesions and the times of sampling, and some of them were identical to those observed in the peripheral blood. These results suggest that the T cell clonal expansions correlate with the disease activities and that the expansion might contribute to the pathogenic lesion formation in SLE.

Adolescent↗
PubMed1997

Effects of YM-14673, a thyrotropin-releasing hormone analogue, injected into the shell and the core of the nucleus accumbens on production of repetitive jaw movements in rats: comparison with the effects of a dopamine D1 and D2 receptor agonist combination.

The present study examined whether the shell and the core of the nucleus accumbens play a differential role in the display of YM-14673-induced jaw movements in rats. For that purpose the effects of YM-14673 were compared to those of a SKF 82958 and quinpirole combination, a dopamine D1 and a D2 receptor agonist respectively, that is known to functionally differentiate these two subregions of the nucleus. Consistent with the previous report, bilateral injections of a mixture of SKF 82958 (5 micrograms) and quinpirole (10 micrograms) into the shell of the nucleus accumbens produced repetitive jaw movements, whereas similar injections of the mixture into the core did not induce such an effect. In contrast, there was no regional difference in the effects of YM-14673 on the production of repetitive jaw movements. Thus, both bilateral injections of YM-14673 (0.1 or 1.0 microgram) into the shell or the core produced similar repetitive jaw movements in a dose-related manner. Moreover, the pattern of oral movements induced by YM-14673 differed from that induced by the mixture of SKF 82958 and quinpirole; frequent tongue protrusions were evident in rats treated with the mixture but were not seen in YM-14673-treated rats. It therefore appears that, unlike the effects of the mixture of dopamine D1 and D2 receptor agonists, the effects of YM-14673 in the shell on the production of rat jaw movements do not differ from the effects of the compound in the core.

Animals↗
PubMed1997

[Carotid intima-media thickness and the occurrence of plaque in centenarians--data from the Tokyo Centenarian Study].

We studied carotid intima-media thickness at non-plaque sites and the occurrence of plaque in 25 centenarians (8 men and 17 women) living in Tokyo. The studies were done by B-mode ultrasonography and the results were compared with those found in 126 healthy subjects (83 men and 43 women) aged 28 to 82 years. The intima-media complexes were diffusely thickened in the centenarians; average thickness at bifurcations and at three sites in each common carotid artery ranged from 0.91 to 1.12 mm. The thickness was not associated with blood pressure or with serum lipid concentration. The thickness in the control group correlated with age, and that relationship fit a second degree equation. The expected values of mean intima-media thickness of the common carotid arteries at age 100 were computed with these equations; the predicted values ranged from 0.92 to 0.98 mm, which are close to the mean values measured in the centenarians (0.95 to 1.05 mm). However, the variations in intima-media thickness were greater in the centenarians. The prevalence of plaque in the centenarians was 40% for the right carotid artery and 36% for the left, but the prevalence among those in the eighth decade of life was 9.5% for both sides; plaque was not found among subjects in the sixth decade of life or younger. These data suggest that the degree of carotid arteriosclerosis is one factor that limits human longevity.

Adult↗
PubMed1997

[Lipid and lipoprotein profile of Japanese centenarians--high prevalence of hypo beta lipoproteinemia].

To study the relationship between lipids and longevity, we examined the level of serum lipids and apolipoproteins, and the susceptibility of low density lipoprotein (LDL) to oxidation of 45 centenarians (15 men, 30 women, mean age 101.1 +/- 1.4) living in the Tokyo metropolitan area. The average levels of total cholesterol (TC), of LDL-C of high-density lipoprotein cholesterol (HDL-C), and of apolipoproteins A1 and B were significantly lower in centenarians than in healthy middle-aged controls. The frequency of hypobeta-lipoproteinemia (apoB < 60 mg/dl) in centenarians was almost ten times as high as in controls. The time course of copper-mediated LDL, oxidation (assessed by monitoring 234 nm diene absorption (lag time)) did not significantly differ between the two groups. Analysis of LDL subfractions by non-denaturated gradient-gel electrophoresis showed a predominance of large, buoyant LDL particles (pattern A) in 75%, and a predominance of small dense LDL particles (pattern B) in 25% of centenarians. We also assessed activities of daily living (ADL) and cognitive function in the centenarians. Centenarians were divided into two groups according to the median ADL score, and were classified into five groups with a scale clinical dementia. In subjects with good ADL scores, the mean concentration of HDL-3-C was significantly higher than in those with poor ADL scores. Average levels of HDL-C were also significantly lower in subjects with moderate or severe dementia than in those with normal cognitive function. These findings suggest that centenarians have protective phenotypes of lipids and lipoproteins that protect them from atheroscierosis.

Activities of Daily Living↗
PubMed1997

[Tokyo Centenarian Study. 4. Apolipoprotein E phenotype in Japanese centenarians living in the Tokyo Metropolitan area].

To examine the relationship between apolipoprotein E (apoE) phenotype and life span, we measured the frequently of the apoE phenotype and allele in 54 Japanese centenarians who lived in the Tokyo metropolitan area in 1994, 1995, and 1996. The control group consisted of 973 subjects, 883 healthy volunteers who were described previously and 90 healthy people who came to the Keio health consulting center. The apoE phenotypes in the centenarians was 2 E2/E2 (3.7%), 5 E2/E3 (9.3%), 38 E3/E3 (70.4%), and 9 3E/E4 (16.7%). No other phenotype was observed. In the control group, the phenotypes were 2 E2/E2 (0.2%), 57 E2/E3 (5.9%) 712 E3/E3 (73.2%), and 179 E3/E4 (18.4%). The frequency of E2 was higher in the centenarians. The frequencies of the apoE allele in the centenarians and the control subjects were epsilon 2 8.3% vs. 3.5%, epsilon 3 83.3% vs. 85.4%, and epsilon 4 8.3% vs. 10.9%. The frequency of the apoE allele differed significantly between centenarians and control subjects (chi 2 = 6.84, p = 0.033). Levels of serum cholesterol and apolipoprotein B were significantly lower in the E2/E2 + E2/E3 centenarians. Studies of the frequency of the apoE allele in Japanese, French, and Finnish subjects showed that epsilon 2 is more frequent and epsilon 4 is less frequent in centenarians. These data show the apoE phenotype may affect life span: epsilon 2 is positively and epsilon 4 is negatively associated with longevity.

Aged↗
PubMed1997

[Tokyo Centenarian Study. 5. Nutritional status of Japanese centenarians].

To establish the guideline for nutrition in the very old, we analyzed biochemical and hematological data from 45 Japanese centenarians living in Tokyo metropolitan area during 1994 and 1995. Levels of cholesterol, HDL-cholesterol, apolipoprotein A1 and B, albumin, prealbumin in serum were lower than in a control group or lower than the reference range, which indicates that these centenarians were undernourished. RBC counts, hemoglobin, and hematocrit were also low in the centenarians. The concentration of albumin correlated positively with those of HDL-cholesterol and apolipoprotein A1, and negatively with concentration of Lp(a). The value for transferrin correlated positively with energy intake and with the concentration of apolipoprotein A1. The concentration of prealbumin correlated positively with the concentration of hemoglobin, hematocrit and the total cholesterol concentration. According to their nutritional status, the centenarians were divided into 2 groups: well-nourished and undernourished. Those who were well-nourished had higher levels of cholesterol, HDL, Hb, and apolipoprotein A1, their levels of ADL and cognitive function were also high. The findings of blood-chemical data in the centenarians may be partly due to undernutrition. Centenarians who were well-nourished were considered to be aging successfully. These results and others previously published indicate that the concentrations of albumin, prealbumin, transferrin and either CRI or IL-6 are useful for nutritional assessment in the very old.

Aged↗
PubMed1996

Beyond oxidized LDL: the initiation and progression of atherosclerosis.

Oxidized-low density lipoprotein (ox-LDL) exhibits various atherogenic properties, such as the formation of foam cells, the recruitment of macrophages into arteries, the promotion of cell growth, the formation of thrombi, and the development of vasoconstriction. Antioxidants inhibit atherosclerosis in cholesterol-fed animals by preventing the recruitment of macrophages into the arteries suggesting that oxidation is important for such recruitment of macrophages, and that it is responsible for early development of atherosclerosis. Calcification and an increase in extracellular matrix (ECM) are frequently observed in advanced atherosclerosis. These processes are active and regulated, not passive and degenerative, and do not appear to be controlled by ox-LDL. The control of calcifications and ECM increase will provide new directions in the treatment of atherosclerosis especially in the advanced stages. Future treatment should include strategies to inhibit the calcification and the increase in ECM.

Antioxidants↗
PubMed1996

[Fluorescence polarization immunoassay and microparticle enzyme immunoassay].

We describe a new clinical laboratory instrument, the Abbott AxSYM, which provides random- and continuous-access testing for immunoassays, 20 onboard reagents, primary tube sampling, and a throughput of 80 to 120 tests per hour. The AxSYM incorporates three separate analytical technologies for processing immunoassays: microparticle enzyme immunoassay, fluorescence polarization immunoassay, and a novel technology known as ion-capture immunoassay. The system incorporates both common and technology-specific subsystems controlled by a real-time software scheduling processor. Tests can be processed in one- or two-step sandwich or competitive formats, with variable pipetting steps, incubation periods, optical read formats, and wash sequences. Menu capabilities include test for hepatitis, retrovirus, tumor markers, fertility markers, thyroid functions, and therapeutic drugs. The time to first result is 15 approximately 25 min for most routine assay and < or = 15 min for stat assays (i.e., creatine kinase MB isoenzyme, human chorionic gonadotropin beta subunit, and therapeutic drugs). AxSYM assay performance for 23 assays was comparable with that of the Abbott IMx and TDx analyzers; specimen correlation data had correlation from 0.99 to 1.10. Within-run imprecision (CV) was 1.5% to 11.4%, with most assays (19 of 23) demonstrating CVs < or = 8.0%.

Fluorescence Polarization Immunoassay↗
PubMed1995

The distribution of TM-316-associated surface antigen on polymorphonuclear leucocytes: an immunoelectron microscopic study.

It has been established that MoAb TM-316 recognizes an epitope on leucocytes and specifically inhibits the chemotactic behavior of leucocytes. In the present paper, the distribution of this epitope on the cell surface and in intracellular organelles was studied by immunoelectron microscopy. Leucocytes separated from the blood of healthy men and from synovial fluid from patients suffering from rheumatoid arthritis were used. They were fixed with a mixture containing paraformaldehyde, glutaraldehyde and picric acid. As the second antibody, goat anti-mouse IgM conjugated to 10 nm gold colloids was employed. In normal specimens, the epitope was found to some extent on the cytoplasmic membrane of neutrophilic leucocytes, but it was only sparsely distributed on eosinophilic and basophilic leucocytes. On activated neutrophilic leucocytes, obtained from the synovial fluid of rheumatoid arthritis patients, the immunolabeling was markedly increased. The number of sites where the epitope occurs on the surface of leucocytes is thus associated with the cell type, and also with the level of activation of the leucocytes. In order to investigate the processing of the antigen, the intracellular localization of the epitope in the neutrophilic leucocytes was also studied. The epitope recognized by TM-316 was also detected in/on the characteristic granules and Golgi stacks.

Antigens↗
PubMed1995

Gq pathway desensitizes chemotactic receptor-induced calcium signaling via inositol trisphosphate receptor down-regulation.

Desensitization of a chemotactic receptor is an adaptive process that terminates inflammation. Although homologous desensitization can be well explained by the action of specific receptor kinases, the mechanisms of heterologous desensitization remain elusive. As an approach to evaluate the roles of Gq pathway in desensitization of calcium signaling, we expressed a constitutively active Gq alpha mutant (Gq alpha Q-L) together with platelet-activating factor (PAF) receptor in Xenopus laevis oocytes. Gq alpha Q-L expression completely attenuated the calcium-sensitive chloride current and the 45Ca release elicited by PAF. The Gq-mediated desensitization could not be ascribed to G protein/receptor uncoupling via receptor phosphorylation, because (i) PAF-induced inositol 1,4,5-trisphosphate (IP3) synthesis was only partially suppressed and (ii) a mutated PAF receptor devoid of all Ser and Thr in the third cytoplasmic loop and in the C-terminal tail was also completely desensitized by Gq alpha Q-L. In Gq alpha Q-L expressing oocytes, microinjection of IP3 failed to elicit the calcium response, and the IP3 receptor, detected by a specific antibody, disappeared. Thus, the Gq-mediated desensitization can be most likely explained by IP3 receptor down-regulation. These novel mechanisms may explain in part heterologous desensitization in chemotactic factor-stimulated inflammatory cells.

Animals↗
PubMed1995

Immunohistochemical identification and characterization of smooth muscle-like cells in idiopathic pulmonary fibrosis.

The interstitium of the fibrotic lung possesses a contractile capability that is unusual for nonmuscle tissue. An abundance of actin filament-laden cells have been demonstrated in animal and human studies of fibrotic lung tissue and have frequently been termed myofibroblasts. The origin and significance of these cells remain unclear. Proliferation of cells with the capability to contract and thereby generate force within the parenchyma is potentially a significant contribution to the increased lung elastic recoil of advanced pulmonary fibrosis. In the present study, we immunohistochemically examined these intermediate phenotypes of filament-laden cells with a focus on those expressing smooth muscle-associated isoforms of actin. The monoclonal antibody HHF35 was used to study the presence and distribution of cells expressing alpha and gamma smooth muscle actin in idiopathic pulmonary fibrosis (IPF). Adjacent sections of tissue from open lung biopsies of eight patients with IPF were stained with a pentachrome stain and with multiple antibodies (HHF35, polyclonal anti-actin, anti-vimentin, anti-keratin, anti-procollagen I, and anti-von Willebrand Factor VIII) to identify specific cell types. In addition, anti-laminin antibody was used to stain basement membrane. Many tightly packed, HHF35-reactive cells were found to be architecturally dissociated from airways and blood vessels in all eight patients with IPF. Some HHF35-reactive bundles were composed of loosely associated cells, and single smooth muscle cell types (SMC) were distributed in the fibrotic interstitium. Interestingly, some of the SMC were distinctly negative for anti-laminin and stained atypically with pentachrome. Moreover, some single SMC were found to be anti-procollagen type I reactive with double staining technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1995

[A case report of a metaplastic carcinoma of the breast diagnosed by the preoperative needle biopsy].

A case of the metaplastic carcinoma, a rare type of the breast cancer, was reported. A 49-year-old woman noticed the left breast lump. Ultrasonography revealed a well circumscribed hypoechoic mass measuring 3 cm in diameter. The preoperative needle biopsy showed the invasive carcinoma with chondrometaplasia. The modified radical mastectomy along with the lymph node dissection was performed. There have been few reports of the metaplastic breast carcinoma diagnosed preoperatively.

Biopsy, Needle↗
PubMed1995

alpha-Tocopherol enhances the hypocholesterolemic action of sesamin in rats.

The effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was examined in rats given a cholesterol-enriched diet. When different levels (0.05 and 0.2%) of sesamin were fed, the supplementation of 1% alpha-tocopherol significantly accentuated the hypocholesterolemic action of sesamin, particularly with the higher sesamin level, although alpha-tocopherol alone did not affect the concentration of serum cholesterol. The dose-dependent promoting effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was confirmed by supplementing different levels (0.2 and 1%) of alpha-tocopherol to a fixed level of sesamin (0.2%). alpha-Tocopherol was still effective at the 0.2% level. The metabolism of sesamin in the liver S9 fraction appeared to be interfered with alpha-tocopherol in vitro, suggesting a possible role of alpha-tocopherol in maintenance of the availability of sesamin.

Animals↗
PubMed1994

Identification of commonly recognized epitopes on a rare autoantigen: poly(ADP-ribose) polymerase.

To analyze mechanisms of autoantibody production, epitope mapping of a rare autoantigen, poly(ADP-ribose) polymerase, was performed. A cDNA fragment (1873 bp long), which was already confirmed to encode the autoepitopes of this protein, was subcloned into a protein expression plasmid pEX. Several deletion mutants were produced by enzymatic treatments of this construct. PCR-amplified cDNA fragments were also individually subcloned into this vector. The recombinant proteins produced in Escherichia coli by these vectors were tested for their respective antigenicities by immunoblotting. It was found that all positive sera tested (seven cases) strongly recognized common epitopes in a restricted region of the molecule. Furthermore, three out of the seven positive sera were found to recognize other parts of the molecule. The data suggest possible mechanisms for the formation of anti-poly(ADP-ribose) polymerase autoantibodies.

Antibody Specificity↗