Search PubMed⌕ Search

Biomedical subjects

H Aihara

Publications and source records attributed to H Aihara.

At least 127 records · Page 7Linked to original sources
PubMed1999

Intrarenal angiotensin converting enzyme inhibition in spontaneously hypertensive rats.

We examined the hypotensive effect of enalapril in relation to the local renin-angiotensin system of the kidney in spontaneously hypertensive rats (SHR). Oral administration of enalapril for 7 days decreased mean arterial blood pressure and renal tissue angiotensin II concentration without affecting plasma angiotensin II concentration in SHR. The enalapril treatment did not affect maximum binding of angiotensin II to renal tubules and glomeruli in SHR. In normotensive Wistar-Kyoto rats, no significant changes in mean arterial blood pressure, renal and plasma angiotensin levels were observed with enalapril treatment. Direct infusion of enalapril into the renal medullary interstitium decreased mean arterial blood pressure in association with the reduction of renal tissue angiotensin II concentration without changes in plasma angiotensin II concentration in SHR. These observations suggest that the inhibition of angiotensin conversion in the kidney is important for the hypotensive action of enalapril.

Administration, Oral↗
PubMed1999

Role of endothelin in deterioration of heart failure due to cardiomyopathy in hamsters: increase in endothelin-1 production in the heart and beneficial effect of endothelin-A receptor antagonist on survival and cardiac function.

BACKGROUND: We previously reported that chronic endothelin (ET) receptor blockade ameliorated the survival rate and cardiac hemodynamics in rats with chronic heart failure (CHF) due to myocardial infarction. However, it remains unclear whether ET-1 is involved in the pathophysiology of cardiomyopathy, which is one of the major causes of CHF. Accordingly, we investigated the production of ET-1 in the heart and the effect of chronic ETA receptor blockade on survival rate and cardiac function in the Bio 14.6 hamster, which is an idiopathic model of CHF caused by cardiomyopathy. METHODS AND RESULTS: We used 52-week-old Bio 14.6 cardiomyopathic hamsters and age-matched F1b normal hamsters. The expression of preproET-1 mRNA and the ET-1 level in the hearts were markedly higher in the cardiomyopathic hamsters than in the normal hamsters. The cardiomyopathic hamsters showed severe CHF, illustrated by lower left ventricular (LV) +dP/dt/Pmax and right ventricular (RV) +dP/dt/Pmax and by higher LV end-diastolic pressure (EDP), RVEDP, and central venous pressure compared with the normal hamsters. Long-term (9 weeks) treatment with an ETA antagonist (TA-0201, 1.3 mg. kg-1. d-1) markedly increased survival of cardiomyopathic hamsters (untreated, 16%; TA-0201-treated, 65.2%; P<0.001). After 6 weeks of treatment, LV +dP/dt/Pmax and RV +dP/dt/Pmax were significantly higher and LVEDP and RVEDP were lower in the TA-0201-treated group than in the untreated group, suggesting that chronic TA-0201 treatment effectively prevented deterioration of cardiac dysfunction. CONCLUSIONS: In the cardiomyopathic hamsters with CHF, the production of ET-1 in the heart was markedly increased, and chronic ETA receptor blockade greatly ameliorated survival and cardiac dysfunction. These results suggest that ET-1 plays an important role in the deterioration of CHF caused by cardiomyopathy, and ETA antagonists may exert therapeutic effects in CHF due to cardiomyopathy.

Animals↗
PubMed1999

A mutant of deleted variant of hepatocyte growth factor (dHGF) with alanine substitution in the N-terminal basic region has higher activity in vivo.

In a previous study, we generated a mutant of dHGF (deleted variant of hepatocyte growth factor), termed #2, with higher specific activity than dHGF in assays of mitogenic activity on rat hepatocytes and America opossum kidney epithelial cells (OK). In the present study, we examine in vivo hepatotropic and renotropic activities of #2 and its distribution to target tissues, liver and kidney. Administration of #2 to normal rats significantly increased serum levels of total protein, albumin, free-cholesterol, and HDL-cholesterol and liver weight in a dose-dependent manner. Analysis of these parameters suggests that #2 is more potent than dHGF as a hepatotropic factor in vivo. In addition, #2 reduced mortality of mercuric chloride-administered mice and the effect was stronger than that of dHGF. When injected to mice, a larger amount of #2 than dHGF was rapidly distributed to the liver. Sixty minutes after injection, the concentrations of #2 in plasma, liver, and kidney were higher than those of dHGF. These distribution properties and the higher mitogenic activity in vitro may explain why #2 exerts more potent in vivo biological activity than dHGF.

Acute Kidney Injury↗
PubMed1999

Suitable image parameters and analytical method for quantitatively measuring cerebral blood flow volume with phase-contrast magnetic resonance imaging.

The aim of this study was to determine suitable image parameters and an analytical method for phase-contrast magnetic resonance imaging (PC-MRI) as a means of measuring cerebral blood flow volume. This was done by constructing an experimental model and applying the results to a clinical application. The experimental model was constructed from the aorta of a bull and circulating isotonic saline. The image parameters of PC-MRI (repetition time, flip angle, matrix, velocity rate encoding, and the use of square pixels) were studied with percent flow volume (the ratio of actual flow volume to measured flow volume). The most suitable image parameters for accurate blood flow measurement were as follows: repetition time, 50 msec; flip angle, 20 degrees; and a 512 x 256 matrix without square pixels. Furthermore, velocity rate encoding should be set ranging from the maximum flow velocity in the vessel to five times this value. The correction in measuring blood flow was done with the intensity of the region of interest established in the background. With these parameters for PC-MRI, percent flow volume was greater than 90%. Using the image parameters for PC-MRI and the analytical method described above, we evaluated cerebral blood flow volume in 12 patients with occlusive disease of the major cervical arteries. The results were compared with conventional xenon computed tomography. The values found with both methods showed good correlation. Thus, we concluded that PC-MRI was a noninvasive method for evaluating cerebral blood flow in patients with occlusive disease of the major cervical arteries.

Adult↗
PubMed1999

[Salazosulfapyridine and 5-aminosalicylic acid agents for the treatment of ulcerative colitis].

Sulfasalazine and 5-aminosalicylic acid are very useful therapeutic agents for the treatment of the inflammatory bowel disease, such as ulcerative colitis or Crohn's disease. However, the mechanism of action of the aminosalicylates remains obscure. Recently, many studies about their mechanism have been performed. As a result, aminosalicylates have been identified to have several antiinflammatory pathways: (1) alterations in eicosanoid metabolism of arachidonic acid; particularly inhibition of leukotrien B4 production, (2)free radical scavengers; scavenging reactive oxygen metabolites or nitric oxide (3)immunologic suppression; inhibition of HLA-DR expression on the intestinal epithelial cells, inflammatory cytokine(IL-1 and IL-2) production, adhesion molecule expression, platelet-activating factor release, or histamine release from mast cell, and so on.

Animals↗
PubMed1998

Gene transfer into muscle by electroporation in vivo.

Among the nonviral techniques for gene transfer in vivo, the direct injection of plasmid DNA into muscle is simple, inexpensive, and safe. Applications of this method have been limited by the relatively low expression levels of the transferred gene. We investigated the applicability of in vivo electroporation for gene transfer into muscle, using plasmid DNA expressing interleukin-5 (IL-5) as the vector. The tibialis anterior muscles of mice were injected with the plasmid DNA, and then a pair of electrode needles were inserted into the DNA injection site to deliver electric pulses. Five days later, the serum IL-5 levels were assayed. Mice that did not receive electroporation had serum levels of 0.2 ng/ml. Electroporation enhanced the levels to over 20 ng/ml. Histochemical analysis of muscles injected with a lacZ expression plasmid showed that in vivo electroporation increased both the number of muscle fibers taking up plasmid DNA and the copy number of plasmids introduced into the cells. These results demonstrate that gene transfer into muscle by electroporation in vivo is more efficient than simple intramuscular DNA injection.

Animals↗
PubMed1998

Establishment and characterization of Japanese encephalitis virus-specific, human CD4(+) T-cell clones: flavivirus cross-reactivity, protein recognition, and cytotoxic activity.

We analyzed the CD4(+) T-lymphocyte responses of two donors who had received Japanese encephalitis virus (JEV) vaccine 6 or 12 months earlier. Bulk culture proliferation assays showed that peripheral blood mononuclear cells (PBMC) responded to JEV antigens (Ag) but also responded at lower levels to West Nile virus (WNV) and dengue virus type 1, 2, and 4 (D1V, D2V, and D4V, respectively) Ag. Five JEV-specific CD4(+) human T-cell clones and one subclone were established from PBMC of these two donors. Two clones responded to WNV Ag as well as to JEV Ag, whereas the others responded only to JEV Ag. Three of five CD4(+) T-cell clones had JEV-specific cytotoxic activity and recognized E protein. The HLA restriction of the JEV-specific T-cell clones was examined. Three clones were HLA-DR4 restricted, one was HLA-DQ3 restricted, and the HLA restriction of one clone was not determined. T-cell receptor analysis showed that these clones expressed different T-cell receptors, suggesting that they originated from different T lymphocytes. These results indicate that JEV vaccine induces JEV-specific and flavivirus-cross-reactive CD4(+) T lymphocytes and that these T lymphocytes recognize E protein. The functions and HLA restriction patterns of these T lymphocytes are, however, heterogeneous.

CD4-Positive T-Lymphocytes↗
PubMed1998

EMG potentials elicited by forehead taps in the sternocleidomastoid muscles and lower leg muscles--a study on patients with vestibular lesions.

The aim of the present study was to determine whether a tap on the forehead evokes a vestibulospinal reflex in the sternocleidomastoid muscles and the lower leg muscles in patients with vestibular lesions. Although first positive-negative short-latency EMG potentials with a mean positive potential peak of about 12.6 ms and a mean negative potential peak of about 17.3 ms were found in the bilateral sternocleidomastoid muscles in normal subjects, they were lacking in patients with vestibular lesions. The first negative short-latency EMG potentials had a mean latency of 48.3 +/- 3.1 ms (onset) to 98.3 +/- 6.3 ms (end) in both gastrocnemius muscles in normal subjects, but they were delayed in patients with vestibular lesions.

Adult↗
PubMed1998

Evaluation of vertical semicircular canal function by the caloric test--a study on patients with benign paroxysmal positional vertigo.

The morbidity of benign paroxysmal positional vertigo (BPPV) was investigated from the functional standpoint by analyzing nystagmus elicited by the caloric test. As a result of an investigation of the three (horizontal, vertical and torsional) components of the nystagmus elicited by the caloric stimulus (cold water), the vertical nystagmus differed in direction between the left and the right ear in 3 out of the 4 BPPV cases. The vertical nystagmus elicited by the caloric stimulus reflected the functions of the anterior and posterior semicircular canals, and investigation of the difference in function between the anterior and posterior semicircular canal from the direction of the vertical nystagmus appeared to be feasible.

Adult↗
PubMed1997

An interaction between a specified surface of the C-terminal domain of RecA protein and double-stranded DNA for homologous pairing.

RecA protein and its homologs catalyze homologous pairing of dsDNA and ssDNA, a critical reaction in homologous genetic recombination in various organisms from a virus, microbes to higher eukaryotes. In this reaction, RecA protein forms a nucleoprotein filament on ssDNA, which in turn binds to naked dsDNA for homology search. We suggested that the C-terminal domain of RecA protein plays a role in capturing the dsDNA. Here, we isolated the C-terminal domain as a soluble form and determined the solution structure by NMR spectroscopy. The overall folding of the NMR structure agrees with that of the corresponding part of the reported crystal structure, but a remarkable difference was found in a solvent-exposed region due to intermolecular contacts in the crystal. Then, we studied the interaction between the C-terminal domain and DNA, and found that significant chemical shift changes were induced in a specific region by titration with dsDNA. SsDNA induced a much smaller chemical shift perturbation. The difference of DNA concentrations to give the half-saturation of the chemical shift change showed a higher affinity of the C-terminal region toward dsDNA. Combined with our previous results, these provide direct evidence that the defined region in the C-terminal domain furnishes a binding surface for DNA.

Amino Acid Sequence↗
PubMed1997

Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel.

ATP-sensitive K+ (KATP) channels are known to play important roles in various cellular functions, but the direct consequences of disruption of KATP channel function are largely unknown. We have generated transgenic mice expressing a dominant-negative form of the KATP channel subunit Kir6.2 (Kir6.2G132S, substitution of glycine with serine at position 132) in pancreatic beta cells. Kir6.2G132S transgenic mice develop hypoglycemia with hyperinsulinemia in neonates and hyperglycemia with hypoinsulinemia and decreased beta cell population in adults. KATP channel function is found to be impaired in the beta cells of transgenic mice with hyperglycemia. In addition, both resting membrane potential and basal calcium concentrations are shown to be significantly elevated in the beta cells of transgenic mice. We also found a high frequency of apoptotic beta cells before the appearance of hyperglycemia in the transgenic mice, suggesting that the KATP channel might play a significant role in beta cell survival in addition to its role in the regulation of insulin secretion.

Adenosine Triphosphate↗
PubMed1997

Electron microscopic study of human immunodeficiency virus type 1 (HIV-1) core structure: two RNA strands in the core of mature and budding particles.

The basic structure of human immunodeficiency virus type 1 (HIV-1) has been investigated morphologically; however, the internal structure of HIV-1 core is not well understood. We studied the internal structures by transmission electron microscopy. We modified the method for electron staining of ultrathin sections and processed electron microscopic photographs using a computer. We confirmed that a mature HIV-1 particle had two copies of RNA strands in a cone-shaped core. These two RNA strands formed a coiling structure and interwound each other, and were already present in the late budding stage.

HIV-1↗
PubMed1997

[Motor functional MRI by spiral scan--compared with GRE].

Recently, functional MRI (fMRI) has been performed in two methods using 1.5 tesla machine. One was performed using gradient recalled echo (GRE), the other was performed using echo planner imaging (EPI). There is a third method for fMRI called spiral scan. This method is applicable without strong gradient magnetic field such as required by EPI. In this study, motor fMRI was performed in ten normal volunteers by both spiral scan and GRE. Less than 1% risk (t-test), spiral scan showed the reactive area more clearly than GRE. And GRE showed higher signal intensity changing ratio than spiral scan, but there was no significant difference between spiral scan and GRE. The acquisition time of spiral scan was 2 seconds per image, and that of GRE was 10.5 seconds. Spiral scan has good temporal resolution and contrast-noise ratio. These are very advantageous for fMRI.

Adult↗
PubMed1996

A possible role of the C-terminal domain of the RecA protein. A gateway model for double-stranded DNA binding.

According to the crystal structure, the RecA protein has a domain near the C terminus consisting of amino acid residues 270-328 (from the N terminus). Our model building pointed out the possibility that this domain is a part of "gateway" through which double-stranded DNA finds a path for direct contact with single-stranded DNA within a presynaptic RecA filament in the search for homology. To test this possible function of the domain, we made mutant RecA proteins by site-directed single (or double, in one case) replacement of 2 conserved basic amino acid residues and 5 among 9 nonconserved basic amino acid residues in the domain. Replacement of either of the 2 conserved amino acid residues caused deficiencies in repair of UV-damaged DNA, an in vivo function of RecA protein, whereas the replacement of most (except one) of the tested nonconserved ones gave little or no effect. Purified mutant RecA proteins showed no (or only slight) deficiencies in the formation of presynaptic filaments as assessed by various assays. However, presynaptic filaments of both proteins that had replacement of a conserved amino acid residue had significant defects in binding to and pairing with duplex DNA (secondary binding). These results are consistent with our model that the conserved amino acid residues in the C-terminal domain have a direct role in double-stranded DNA binding and that they constitute a part of a gateway for homologous recognition.

Adenosine Triphosphate↗