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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 325 records · Page 18Linked to original sources

The role of gamma delta T cells in priming macrophages to produce tumor necrosis factor-alpha.

The secretion of tumor necrosis factor (TNF)-alpha from macrophages is regulated by both priming and triggering signals. We found that macrophages from mice lacking gamma delta T cells [T cell receptor (TCR) delta-/- mice], which lack the gene encoding the delta chain, produced only small amounts of TNF-alpha in response to lipopolysaccharide (LPS) and showed a reduced level of expression of CD14. Pre-incubation of macrophages from TCR delta-/- mice with gamma delta T cells from their TCR delta +/- littermates restored their capacity to produce TNF-alpha in response to LPS. The priming activity of gamma delta T cells was in part inhibited by neutralizing anti-interferon (IFN)-gamma monoclonal antibodies. Collectively, these results suggest that gamma delta T cells play a role in priming macrophages to a steady state of activation via IFN-gamma secretion, which allows them to produce TNF-alpha when exposed to LPS.

Animals↗

Abnormal T cell activation and skewed T cell receptor V beta repertoire usage in Japanese patients with idiopathic portal hypertension.

Idiopathic portal hypertension (IPH), a disorder of unknown etiology, is characterized by a noncirrhotic portal hypertension associated with splenomegaly, hypersplenism, and anemia. We examined the surface phenotypes of T cells and the T cell receptor V beta repertoire in patients with IPH. The T cells in peripheral blood samples and from spleens showed a marked increase in frequencies of HLA-DP(+)- and HLA-DR(+)-activated T cells and the observed high frequencies in the blood were to a considerable extent reduced after splenectomy. Thus, the continuous activation of T cells may occur initially in the spleen. Investigation of T cell receptor V beta repertoire revealed a significant skewing of V beta 9 and V beta 11 in both peripheral blood and splenic T cells and V beta 12 in splenic T cells. The IPH may be a disease mediated by a continuous stimulation with either a certain antigen or more likely a superantigen.

Adult↗

High thoracic neurinoma mimicking femoral neuralgia.

We report a case of spinal neurinoma at a high thoracic level, whose main presentation was intractable pain in a body part innervated by the right femoral nerve. Sensations of pain and temperature were impaired in the right thigh, but usual symptoms of myelopathy were undetectable. In conjunction with the other reports, this case suggests that spinal tumors at high thoracic levels can produce remote symptoms mimicking peripheral neuropathy such as femoral or sciatic neuralgia.

Femoral Nerve↗

Biomedical and biotechnological applications of PEG- and PM-modified proteins.

Chemical modification of proteins and other bioactive molecules with polyethylene glycol (PEG) or its derivatives (PM) can be used to tailor molecular properties to particular applications, eliminating disadvantageous properties or conferring new molecular functions. Complexes of therapeutic proteins and PEG or PM show reduced immunoreactivity, prolonged clearance times and improved biostability. Modification with PEG can also increase the solubility and activity of enzymes in organic solvents, thus extending their potential for application in organic syntheses and biotransformation processes.

Amino Acid Sequence↗

Mechanisms of angiotensin II formation in humans.

Various organs, including the heart and blood vessels, apparently contain tissue renin-angiotensin systems. Through autocrine and paracrine activity, locally produced angiotensin II (Ang II) may well play an important role in cardiovascular homeostasis; in pathological conditions. Ang II may also contribute to the remodelling of the heart and vasculature. In addition to angiotensin converting enzyme (ACE), a cardiac Ang II forming serine proteinase (human heart chymase) has been identified in the left ventricle of the human heart. The different cellular and regional distributions of ACE and chymase in the heart as well as in the blood vessels suggest distinct pathophysiological roles for these two Ang II forming enzymes. Several reports indicate that both ACE-dependent and ACE-independent Ang II formation appear to occur in hypoxic or ischaemic hearts or blood vessels in vivo and seem to be involved in the pathological changes seen in these organs. However, chymase-dependent Ang II formation--which is chymostatin sensitive but aprotinin insensitive--does not explain all ACE-independent Ang II formation. Therefore, it is important to elucidate the mechanisms of tissue Ang II formation in humans and their contribution to the pathophysiological changes in cardiovascular disease.

Angiotensin II↗

Functional CD4+ T cell subsets defined by expression of CD45RC and NTA260 antigens and age-associated polarization in murine lupus.

Using two mAb, one specific to the alternative exon 6-dependent epitope of CD45 molecules (JH6.2) and one a natural thymocytotoxic autoantibody (NTA) with an unknown reactive epitope (NTA260), we subdivided splenic CD4+ T cells from 2-month-old BALB/c mice into five phenotypically distinct subsets. CD45RC+NTA260- (S I) cells were phenotypically analogous to CD4+ T cells predominating in newborn mice and produced a significant amount of IL-2, but not so IL-4, IL-10 or IFN-gamma when stimulated with immobilized anti-CD3 mAb in vitro. They appeared to consist mainly of naive ThP cells. The CD45RC+NTA260+ (S II) subset also produced IL-2, but not other cytokines; however, the IL-2 levels produced were much higher than seen with the S I subset, thereby suggesting the predominance of further maturated ThP cells. The CD45RC-NTA260+ (S III) subset mainly produced IL-4, IL-10, IFN-gamma and less IL-2, and contained memory cells that helped the secondary antibody response to a recall antigen, and hence contained Th2 and probably a mixture of Th0 and Th1 cells. The CD45RC-NTA260- (S IV) subset was a poor responder to the immobilized anti-CD3 mAb. The CD45RCbrightNTA260dull (S V) subset consisted of a small number of cells that were phenotypically analogous to activated CD4+ T cells. While an age-associated decrease in the proportion of S I and less markedly in S II and in turn increase in S III subsets of CD4+ T cells occurred in normal BALB/c mice, autoimmune disease-prone (NZB x NZW)F1 mice showed a marked age-associated decrease in the proportion of not only S I, II but also III subsets. As aged (NZB x NZW)F1 mice carry CD4+ T helper cells for IgG anti-DNA antibody production, such age-associated polarization to the S IV subset appears to be critical in the pathogenesis of autoimmune disease in these mice.

Aging↗

Lipid peroxidation as an indicator of biocompatibility in haemodialysis.

Peroxidation of cell membrane (phosphatidylcholine hydroperoxide, PCOOH) was quantitatively assessed using a chemiluminescence-HPLC system to clarify whether haemodialysis patients are damaged by oxidative stress. Patients were divided into two groups, one dialysed with conventional cellulose membranes, and the other with cellulose triacetate for 3 months, subsequently followed by a crossover study of each membrane for 3 more months. The mean value of PCOOH in haemodialysis patients was 508.5 +/- 208.7 pmol/ml (P < 0.01 vs normal controls), which showed a statistically insignificant tendency to increase during each haemodialysis session of 4 h. Two years after commencing haemodialysis, PCOOH was maintained within almost the same range, but significantly greater than normal. There was no significant tendency between an index of aortic sclerosis and plasma PCOOH. However, three patients using conventional cellulose membranes died of myocardial infarction. Plasma PCOOH increased after the commencement of haemodialysis. This tendency was more notable in patients using conventional cellulose membrane compared to the cellulose triacetate. Cellulose triacetate, which we thought to be more biocompatible, did not necessarily produce lipid peroxide. We conclude that it is very important to check production of oxygen radicals when developing new membranes.

Biocompatible Materials↗

Identification of influenza C virus phosphoproteins.

The HMV-II cells infected with influenza C virus were labeled with inorganic [32P]phosphate to identify phosphorylated proteins. Analysis by radioimmunoprecipitation with antiviral serum or monoclonal antibodies revealed that three major structural proteins of the virus, hemagglutinin-esterase (HE), nucleoprotein (NP), and matrix protein (M1) are all phosphorylated in both infected cells and virions. It was also observed that, in the presence of trypsin (10 micrograms/ml), the unphosphorylated form of the HE glycoprotein was cleaved efficiently whereas the phosphorylated form was not, raising the possibility that phosphorylation of HE may influence its susceptibility to degradation by proteolytic enzymes.

Antibodies, Monoclonal↗

Inhibition of 1,2-dimethylhydrazine-induced oxidative DNA damage by green tea extract in rat.

Following subcutaneous injection of 1,2-dimethylhydrazine (DMH), which is carcinogenic to rat colon and liver, to Sprague-Dawley rats, a significant increase of 8-hydroxydeoxyguanosine (8-OHdG) was observed in the DNA of colonic mucosa and liver. The 8-OHdG formation reached the maximal level at about 24 h after the DMII injection. On the other hand, no increase of 8-OHdG was observed in the DNA of the kidney. Drinking green tea extract (GTE) for ten days prior to the DMH injection significantly inhibited the formation of 8-OHdG in the colon. These findings demonstrate that DMH causes oxidative damage to the DNA of its target organ, and that GTE protects colonic mucosa from this oxidative damage.

1,2-Dimethylhydrazine↗

A novel method to study the hyphal phase of Candida albicans and to evaluate its hydrophobicity.

As little is known about the surface properties of the hyphal phase of the dimorphic fungus Candida albicans due to the difficulty in examining the latter phase in isolation, a novel method was designed to compartmentalize the two phases of the yeast using a commercially available filter-type device-Chemotaxicell. When yeast cells in the blastospore phase were incubated in filter chambers of Chemotaxicell submerged in hyphal-induction media, hyphae traversed through the pores of the filter into the exterior of the chamber enmeshing the entire outer filter surface, after 72 h of incubation. However, the inner or the chamber surface of the filter comprised mainly blastospores. The hydrophobicity of the two morphologic phases of the yeast was then compared using this method, by contact angle measurement. When the 72-h specimens with matted hyphal elements were evaluated, the contact angles varied depending on the incubation medium (such as TC 199 or serum), and in each case hydrophobicity of the hyphal phase was significantly higher than the blastopore phase yeasts. This simple, reproducible method should help not only in evaluating the properties of the hyphal elements of C. albicans but also in studying parameters such as saliva and serum, which are known to affect hyphal formation in vivo.

Analysis of Variance↗

[A case of toxic shock-like syndrome due to Streptococcus pyogenes].

A case of toxic-shock syndrome due to Streptococcus pyogenes is reported. A 76-year-old female was admitted with complaints of fevers and chills. She had been suffering from cellulitis on her right dorsum pedis for 7 months. Laboratory data on admission showed elevated values of WBC, CRP, and dysfunction of the liver and kidney. She was diagnosed as sepsis due to the cellulitis, and was treated with PIPC and FMOX. However, several hours after admission, her blood pressure decreased and oliguria appeared. Bacteriological examinations from the blood and the cellulitis revealed group A beta-hemolytic Streptococcus which gave streptococcal pyrogenic exotoxin (T-28, SPE.B + C). She died 23 hours after her admission in spite of changing antibiotics to a high-dose of PC-G therapy. This is one of the rare cases of toxic shock-like syndrome due to Streptococcus pyogenes from the cellulitis of the dorsum pedis.

Aged↗

Blockade of beta-adrenoceptor in control of blood pressure in fowl.

Several avian species show elevated blood pressure (BP) and spontaneous atherogenesis in the aorta and other large arteries. The BP appears to be influenced by age, sex (higher in males), environment, and diet in some species. We reported previously that mean aortic pressure and heart rate, but not plasma renin activity (PRA), of conscious female domestic fowl were markedly reduced by propranolol. In the present study, we aimed to determine in conscious roosters whether 1) hypotension evoked by atenolol or practolol, which selectively inhibit cardiac beta-receptors in mammals, is more potent than that evoked by propranolol, and 2) the renin-angiotensin (ANG) system and/or catecholamines are involved in beta-adrenoceptor antagonist-induced hypotension. Mean arterial pressure (171.2 +/- 3.5 mmHg) and heart rate (281 +/- 4 beats/min) of chronically cannulated roosters (n = 38) were markedly reduced by acute infusion or repeated injections (14 days) of propranolol, atenolol, or practolol, but not by SQ-14,225 (ANG-converting enzyme inhibitor) or [Sar1, Thr8]ANG II (nonselective ANG receptor antagonist). None of the beta-adrenoceptor blockers, however, showed cardioselectivity. The resting PRA of conscious roosters (1.27 +/- 0.09 ng.ml-1.h-1, n = 38) was low and did not change significantly after chronic or acute treatment with beta-adrenoceptor blockers except for a slight decrease induced by practolol. PRA increased after SQ-14,225. The plasma levels (pg/ml) of norepinephrine (701.9 +/- 76.0), epinephrine (337.2 +/- 57.1), and dopamine (299.1 +/- 39.0) of conscious roosters were further increased by propranolol. Practolol also increased dopamine significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Polyethylene glycol-modified avidin: a novel agent for the selective extraction of biotinylated immune-complex in an aqueous two-phase system.

Chicken avidin was chemically modified with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine (activated PEG2) to form PEG-avidin. The PEG-avidin, in which 78% of the amino groups were modified, retained 49% of the active biotin-binding sites. The modified avidin was partitioned preferentially into the PEG-phase in an aqueous two-phase system (PEG/dextran). Using PEG-avidin, the immune-complex formed between biotinylated anti-mouse IgG and its antigen IgG (mouse) molecules, was successfully transferred into the PEG-phase in an aqueous two-phase system. This finding leads to the effective isolation of a specific antigen among various kinds of antigens by partitioning with a two-phase system using PEG-avidin.

Animals↗

Comparable effects of angiotensin II and converting enzyme blockade on hemodynamics and cardiac hypertrophy in spontaneously hypertensive rats.

Angiotensin-converting enzyme inhibitors may regress left ventricular hypertrophy (LVH) without decreasing blood pressure (BP). The aim of the present study was to compare the effects of low and high doses of lisinopril and the angiotensin II receptor antagonist TCV116 (TCV) on LVH and hemodynamics in spontaneously hypertensive rats (SHR). Lisinopril (0.5 and 3 mg/kg per day) and TCV (0.3 mg/kg per day) were given to 8-week-old male SHR daily for 2 weeks. Untreated SHR and Wistar-Kyoto rats (WKY) served as controls. Untreated SHR had a greater left ventricular (LV) weight than WKY (p < 0.01). Lisinopril (3 mg/kg per day) decreased both LV weight and BP. Lisinopril (0.5 mg/kg per day) significantly decreased LV weight, but not BP. In contrast, although TCV significantly decreased BP, LVH was not suppressed. Renal blood flow (RBF) in untreated SHR was less than that in WKY (p < 0.05), but was increased with either lisinopril (3 mg/kg per day)-treated rats (p< 0.05). These findings suggest that factors other than afterload reduction play a role in the regression of LVH with lisinopril, whereas a longer duration of treatment and/or a higher dose may be necessary with TCV. Despite the decrease in BP, TCV normalized RBF in SHR, perhaps due to the blockade of renal angiotensin II.

Angiotensin II↗

Absolute configuration of a new mosquito repellent, (+)-eucamalol and the repellent activity of its epimer.

(+)-Eucamalol (1) and (-)-1-epi-eucamalol (2) were synthesized from (S)-(-)-perillaldehyde to determine the absolute configuration of 1, the structure of natural (+)-eucamalol being determined to be (1R,6R)-(+)-3-formyl-6-isopropyl-2-cyclohexen-1-ol. (+)-Eucamolol (1) and its 1-epimer (2) exhibited significant repellent activity against Aedes albopictus, and inhibited its feeding as well as DEET.

Aedes↗