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Biomedical subjects

M Ohishi

Publications and source records attributed to M Ohishi.

At least 73 records · Page 4Linked to original sources
PubMed1999

Roles of AT1 and AT2 receptors in the hypertensive Ren-2 gene transgenic rat kidney.

Adult Ren-2 gene transgenic rats, TGR(mRen-2)27, exhibit elevated circulating and kidney angiotensin II (Ang II) levels in the presence of severe hypertension. The aim of this study was to examine whether AT1 and AT2 receptors in the kidney and renal hemodynamic and tubular responses to blockade of these receptors were altered in the Ren-2 gene transgenic rats during the maintenance phase of hypertension. Renal AT1 and AT2 receptors were mapped by in vitro autoradiography (n=8), and the effects of blockade of these receptors on mean arterial pressure (MAP), heart rate (HR), and renal cortical (CBF) and medullary blood flows (MBF) were studied in anaesthetized, adult age-matched male homozygous TGR rats (n=12) and Sprague-Dawley (SD) rats (n=7). TGR rats showed higher basal MAP (P<0.001), heart and kidney weight (P<0.001), plasma renin activity (P<0.05) and plasma Ang II level (P<0.05), and CBF (P<0.05) and MBF (P<0.05) than SD rats. AT1 receptor binding was significantly increased in the glomeruli, proximal tubules, and the inner stripe of the outer medulla of TGR rats (P<0.01), while the AT2 receptor binding was low at all renal sites of TGR and SD rats. Immunohistochemistry revealed that this increased AT1 receptor labeling occurred mainly in vascular smooth muscle layer of intrarenal blood vessels including afferent and efferent arterioles, juxtaglomerular apparatus, glomerular mesangial cells, proximal tubular cells, and renomedullary interstitial cells (RMICs) in the transgenic rats. Blockade of AT1 receptors with losartan in TGR rats markedly reduced MAP to the normotensive level (P<0.001) without altering HR. Both CBF (P<0.005) and MBF (P<0.05) were significantly increased by losartan in the transgenic rats. By contrast, losartan only caused a smaller decrease in MAP and an increase in renal CBF in SD rats (P<0.05). PD 123319 was without any renal effect in both SD and TGR rats. These findings suggest that markedly increased AT1 receptors in renal vasculature, glomerular mesangial cells, and RMICs in the presence of fulminant hypertension and elevated circulating and tissue Ang II levels may play an important role in the maintenance of hypertension in the Ren-2 gene transgenic rats.

Angiotensin I↗
PubMed1999

Activation of the brain angiotensin system by in vivo human angiotensin-converting enzyme gene transfer in rats.

The possibility of the brain-specific expression of a component of the renin-angiotensin system was evaluated in the present study. We used the hemagglutinating virus of Japan-liposome complex to transfect human angiotensin-converting enzyme (ACE) cDNA, driven by the cytomegalovirus enhancer and beta-actin promoter, into the lateral cerebroventricle of male Sprague-Dawley rats. We evaluated the time course of hemodynamics, the tissue levels of angiotensin (Ang) II and vasopressin, and ACE activity. Intracerebroventricular transfection of the human ACE gene increased both blood pressure and heart rate. Transfected rats exhibited higher concentrations of brain Ang II and increased brain ACE activity. This activation of the brain angiotensin system was accompanied by increased vasopressin production. The increases in blood pressure and heart rate were abolished by intracerebroventricular administration of an ACE inhibitor or Ang II type 1 receptor antagonist. The expression of the transgene was widely distributed in the periventricular cell layer, the cortex, the hypothalamic nuclei, and the brain stem. Expression in the neuronal cells persisted for up to 14 days. Thus, this hemagglutinating virus of Japan-liposome method is a highly efficient system for gene delivery and is extremely useful for functional gene transfection. This novel hypertensive model may enable characterization of the functions of the renin-angiotensin system in the brain and determination of its role in the pathogenesis of hypertension.

Angiotensin II↗
PubMed1999

Pharmacogenetic analysis of the effect of angiotensin-converting enzyme inhibitor on restenosis after percutaneous transluminal coronary angioplasty.

Angiotensin-converting enzyme (ACE) inhibitors are reported to prevent neointimal formation after balloon injury in animal models, but in most prospective studies in humans, ACE inhibitors failed to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA). The ACE genotype assigned by an insertion/deletion (I/D) polymorphism is known to affect the potency of ACE inhibitors in several renal diseases. The authors attempted to clarify whether the effect of ACE inhibitors on restenosis might be modified by the ACE genotype. A total of 126 patients was randomly and prospectively assigned to the control group and the imidapril group. In the imidapril group, patients received 5 mg imidapril daily, starting 1 day before PTCA and continuing for 3 to 6 months. Forty-six control (65 vessels) and 32 imidapril patients (43 vessels) completed the study. The minimal lumen diameter before and after the procedure did not differ significantly among the groups with the three genotypes (II, ID, and DD) in both the control and imidapril groups. Late luminal loss during the follow-up period was not related to the ACE genotype in the control group but was significantly related in the imidapril group (II, 0.63+/- 0.19 mm; ID + DD, 1.12+/-0.14 mm, p<0.05). Furthermore, in the II genotype, imidapril significantly reduced late loss and restenosis rate as defined by most of the frequently used definitions. In conclusion the ACE I/D polymorphism may influence the effect of ACE inhibitors in preventing restenosis after PTCA.

Aged↗
PubMed1998

Abundances of ethylene oxide and acetaldehyde in hot molecular cloud cores.

We have searched for millimetre-wave line emission from ethylene oxide (c-C2H4O) and its structural isomer acetaldehyde (CH3CHO) in 11 molecular clouds using SEST. Ethylene oxide and acetaldehyde were detected through multiple lines in the hot cores NGC 6334F, G327.3-0.6, G31.41+0.31, and G34.3+0.2. Acetaldehyde was also detected towards G10.47+0.03, G322.2+0.6, and Orion 3'N, and one ethylene oxide line was tentatively detected in G10.47+0.03. Column densities and rotational excitation temperatures were derived using a procedure which fits the observed line intensifies by finding the minimum chi 2-value. The resulting rotational excitation temperatures of ethylene oxide and acetaldehyde are in the range 16-38 K, indicating that these species are excited in the outer, cooler parts of the hot cores or that the excitation is significantly subthermal. For an assumed source size of 20", the deduced column densities are (0.6-1)x10(14) cm-2 for ethylene oxide and (2-5)x10(14) cm-2 for acetaldehyde. The fractional abundances with respect to H2 are X[c-C2H4O]=(2-6)xl0(-10), and X[CH3CHO]=(0.8-3)x10(-9). The ratio X[CH3CHO]/X[c-C2H4O] varies between 2.6 (NGC 6334F) and 8.5 (G327.3-0.6). We also detected and analysed multiple transitions of CH3OH, CH3OCH3, C2H5OH, and HCOOH. The chemical, and possibly evolutionary, states of NGC 6334F, G327.3-0.6, G31.41+0.31, and G34.3+0.2 seem to be very similar.

Acetaldehyde↗
PubMed1998

Long-term outcomes of nonsurgical treatment in nonreducing anteriorly displaced disk of the temporomandibular joint.

OBJECTIVES: The aim of this study was to evaluate long-term outcomes of nonsurgical treatment in patients with persistent anterior disk displacement without reduction of the temporomandibular joint. STUDY DESIGN: Thirty-five patients were treated with occlusal splints, and 12 patients underwent additional occlusal treatments after splint treatment. These patients were evaluated clinically and radiographically. At least 2 years after the treatment, the 34 patients' symptoms were assessed with the use of a questionnaire. RESULTS: The mean maximal interincisal distance (MID) was 27.6 mm before treatment and 44.4 mm at the end of treatment (p < 0.001). Before the treatment, all 35 patients had complained of pain, and mild pain persisted in 9 patients at the end of treatment. Flattening of the condylar head and of the articular eminence increased in prevalence from 12.1% and 9.1%, respectively, before treatment to 54.5% and 51.5%, respectively, at the time of follow-up observation. At the time of the survey, the mean self-reported MID was 46.8 mm (p < 0.01). CONCLUSIONS: After the nonsurgical treatment, the clinical signs and symptoms improved significantly, although the prevalence of osteoarthrotic findings increased.

Adolescent↗
PubMed1998

A follow-up of rhabdomyosarcoma of the infratemporal fossa region in adults based on the magnetic resonance imaging findings: case reports.

Two adult patients with rhabdomyosarcoma of the infratemporal fossa region were evaluated by computed tomography and magnetic resonance imaging both before and after treatment. Successful treatment accompanied by reduction of the tumor mass as a result of chemotherapy was demonstrated in one patient. In the other patient a subsequent increase in the tumor mass was documented. Information on not only the size but also the internal architecture of the tumor may be useful when tumor response to therapy is being investigated. Magnetic resonance imaging is recommended as a method for outcomes evaluation in adult rhabdomyosarcoma cases.

Adult↗
PubMed1998

Range of motion of the temporomandibular joint in rheumatoid arthritis: relationship to the severity of disease.

The purpose of this study was to determine the frequency and nature of temporomandibular joint (TMJ) involvement in rheumatoid arthritis (RA) patients with symptoms in this joint, and to investigate the relationship of symptoms to the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and Steinbrocker stage. Clinical examination of the range of motion of the TMJ was performed in 218 RA patients. In addition, correlations between the maximal mouth opening and the severity of RA were studied. Restriction in opening the mouth (defined as < or = 30 mm movement in the central incisor region from the fully occluded to maximally open positions) was observed in 12.8% of the RA patients (28/218). The CRP, ESR and Steinbrocker stage were all correlated with maximal opening (p < 0.05). There was a positive correlation between the severity of RA and the range of motion of the jaw.

Adult↗
PubMed1998

Biochemical and functional properties of lysine-specific cysteine proteinase (Lys-gingipain) as a virulence factor of Porphyromonas gingivalis in periodontal disease.

The oral anaerobic bacterium Porphyromonas gingivalis has been implicated as a major etiologic agent of progressive periodontal disease. A novel lysine-specific cysteine proteinase, termed "Lys-gingipain," was purified from the culture supernatant of the Arg-gingipain-deficient mutant of P. gingivalis (KDP112) by a simple method including immunoaffinity chromatography. The purified enzyme was found to be composed of a single polypeptide of Mr=51,000. Analysis of the enzymatic properties revealed several distinctive features of this enzyme. The proteolytic activity was remarkably activated by thiol-reducing agents and inhibited by idoacetamide, idoacetic acid, and leupeptin. The enzyme was also inhibited by the chloromethyl ketones of tosyl-L-lysine and tosyl-L-phenylalanine. However, internal protease inhibitors, such as cystatins and alpha1-antichymotrypsin, had no effect on the activity, suggesting its resistance to normal host defense systems in vivo. Despite its narrow specificity for synthetic substrates containing Lys in the P1 site, the enzyme extensively degraded human type I collagen and immunoglobulins G and A (both serum and secretory types). Most important, the enzyme was able to disrupt the functions of polymorphonuclear leukocytes, as shown by its inhibitory effect on the generation of active oxygen species from the activated cells. These results suggest that Lys-gingipain, like Arg-gingipain, plays a crucial role as a virulence factor from P. gingivalis in the development of periodontal disease via the direct destruction of periodontal tissue components and the disruption of normal host defense mechanisms.

Adhesins, Bacterial↗
PubMed1998

Mapping tissue angiotensin-converting enzyme and angiotensin AT1, AT2 and AT4 receptors.

BACKGROUND: The renin-angiotensin system (RAS) functions as both a circulating endocrine system and a tissue paracrine/autocrine system. As a circulating peptide, angiotensin II (Ang II) plays a prominent role in blood-pressure control and body fluid and electrolyte balance by acting on the AT1 receptor in the brain and peripheral tissues. As a paracrine/autocrine peptide, locally formed Ang II also plays additional roles in tissues involving the regulation of regional haemodynamics, cell growth and remodelling, and neurotransmitter release. Evidence is emerging that Ang II is not the only active peptide of the RAS, and other Ang II fragments may also have important biological activities. OBJECTIVES: To provide a morphological basis for understanding novel actions of angiotensin-converting enzyme (ACE), Ang II and related peptides in tissues, this article will review the localization of ACE and AT1, AT2 and AT4 receptors in the central nervous system, blood vessels and kidney. RESULTS AND CONCLUSION: Autoradiographic mapping of the major components of the RAS has proved a valuable strategy to reveal, or suggest, cellular sites of novel actions for Ang II and related peptides in tissues. First, colocalization of ACE and AT1 receptors in the substantia nigra, the caudate nucleus and putamen of human and rat brain, which contain the dopamine-synthesizing neurons, suggests that the central RAS may be important in modulating central dopamine release. Secondly, the distribution of AT4 receptors with a striking association with cholinergic neurons, motor and sensory nuclei in the brain reveals that Ang IV may modulate central motor and sensory activities and memory. Thirdly, the occurrence of high levels of ACE and AT1 and/or AT2 receptors in the adventitia of blood vessels suggests important paracrine roles of the vascular RAS. Finally, the identification of abundant AT1 receptor and elucidation of its roles in the renomedullary interstitial cells of the kidney may provide a new impetus to study further the role of Ang II in the regulation of renal medullary function and blood pressure. Overall, circulating and locally produced Ang II and related peptides may exert a remarkable range of actions in the brain, kidney and cardiovascular system through multiple angiotensin receptors.

Animals↗
PubMed1998

[Vascular endothelial cells and renin-angiotensin system].

The vascular renin-angiotensin system (RAS) is regulated independently from circulating RAS and plays a role in the local regulation of vascular tone, the modulation of sympathetic activity and vascular remodeling. Endothelial cells are a major source of angiotensin converting enzyme (ACE), which produces angiotensin II and degrades bradykinin, in normal arteries. Mechanical stress such as transmural pressure, stretch stress and shear stress appear to contribute to the regulation of endothelial ACE activity. In contrast, vessels with intimal proliferation such as atheromatous plaque and neointima following balloon injury show expression of ACE in smooth muscle cells and macrophages in the intimal lesions. Activation of ACE in intimal SMC may relate to a phenotypic change of SMC from the contracting type of the synthetic type. Activation of ACE in macrophages is also related to the transformation of macrophages from monocytes. Concerning the role of the activated RAS, elevated blood pressure and vascular tonus by angiotensin II are candidates of vascular injury and plaque rupture. Angiotensin II stimulates migration and proliferation of smooth muscle cells and production of extracellular matrix. Furthermore, angiotensin II increases oxidized-LDL which may be related to the forming of macrophages. These evidence suggest that activation of vascular RAS following endothelial dysfunction/injury play an important role in the pathogenesis of vascular remodeling and atherosclerosis.

Animals↗
PubMed1997

Upregulation of angiotensin-converting enzyme during the healing process after injury at the site of percutaneous transluminal coronary angioplasty in humans.

BACKGROUND: Balloon injury models in rat have shown enhanced expression of ACE in the developing neointima. However, neointimal lesions in human coronary arteries are complex due to atherosclerosis and different types of wall laceration. This study was designed to investigate whether ACE is present in the neointima of humans, including patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: Thirty-seven sites with angioplasty injury, obtained at autopsy, were studied using immunocytochemical techniques. Sites with injury limited to a fibrous plaque and those with injury extending into the media (<2 months after PTCA) showed fibrocellular repair tissue composed mainly of smooth muscle cells that were distinctly positive for ACE. In cellular reactions at the site of injury limited to the atheromatous plaque (<2 months after PTCA), the expression of ACE appeared first in accumulated macrophages; once smooth muscle cells appeared in the repair tissue, they also expressed ACE. At a later stage (3 months after PTCA), the number of cells with ACE expression decreased markedly; from 7 months on, ACE was no longer expressed within the repair tissue. Basically, there were no differences with regard to ACE expression during the healing process after PTCA between segments with and those without angiographic evidence of restenosis. CONCLUSIONS: These results show that PTCA injury in humans results in upregulation of ACE at sites of active repair and, therefore, ACE could play an important role as one of the mediators of the healing process after PTCA.

Aged↗
PubMed1997

Detection of interstellar ethylene oxide (c-C2H4O).

We report the identification of 10 transitions that support the detection of the small cyclic molecule ethylene oxide (c-C2H4O) in Sgr B2N. Although one of these transitions is severely blended, so that an accurate intensity and line width could not be determined, and two other lines are only marginally detected, we have done Gaussian fits to the remaining seven lines and have performed a rotation diagram analysis. Our results indicate a rotation temperature T(rot) = 18 K and a molecular column density N(c-C2H4O) = 3.3 x 10(14) cm-2, corresponding to a fractional abundance relative to molecular hydrogen of order 6 x 10(-11). This is a factor of more than 200 higher than the abundance for this molecule suggested by the "new standard" chemistry model of Lee, Bettens, & Herbst. This result suggests that grain chemistry might play an effective role in the production of c-C2H4O. No transitions of this molecule were detected in either Sgr B2M or Sgr B2NW.

Astronomical Phenomena↗
PubMed1997

Hydrogenation of interstellar molecules: a survey for methylenimine (CH2NH).

Methylenimine (CH2NH) has been convincingly detected for the first time outside the Galactic center as part of a study of the hydrogenation of interstellar molecules. We have observed transitions from energy levels up to about 100 K above the ground state in the giant molecular clouds W51, Orion KL and G34.3 + 0.15. In addition, CH2NH was found at the " radical-ion peak" on the quiescent ridge of material in the Orion molecular cloud. The abundance ratio CH2NH/HCN at the radical-ion peak agrees with the predictions of recent gas-phase chemical models. This ratio is an order of magnitude higher in the warmer cloud cores, suggesting additional production pathways for CH2NH, probably on interstellar grains.

Astronomical Phenomena↗
PubMed1997

Nuclear DNA fragmentation and expression of Bcl-2 in primary biliary cirrhosis.

It is uncertain whether or not apoptosis is involved in the pathogenesis of primary biliary cirrhosis (PBC). The aims of this study were to assess the nuclear DNA fragmentation and expression of Bcl-2 in the biliary epithelial cells (BECs) and in the hepatocytes of PBC. Additionally, the effects of ursodeoxycholic acid (UDCA) on DNA fragmentation and Bcl-2 expression in PBC were evaluated. Liver tissue specimens from 35 PBC patients were examined by in situ nick-end labeling to detect any nuclear DNA fragments, and by immunohistochemistry for Bcl-2. Ten of these patients underwent a second liver biopsy after the treatment with UDCA. Sixteen histologically normal liver tissues and 17 chronic viral hepatitis C (CVHC) samples were chosen as controls. DNA fragmentation in BECs was more frequently found in PBC than in CVHC and more frequently than in the normal controls (both P < .05), and fragmentation in the hepatocytes of PBC more frequently than in normal controls (P < .01). Bcl-2 expression was more frequently found in both the BECs and hepatocytes of PBC than in the controls. UDCA significantly decreased the DNA fragmentation in BECs (P < .05) and the positivity for Bcl-2 in BECs (P < .01), although no significant decrease was found in hepatocytes. In conclusion, de novo Bcl-2 expression in hepatocytes of PBC was shown, and the increased nuclear DNA fragmentation and the Bcl-2 expression both in BECs and in hepatocytes may reflect apoptotic stress, although nuclear DNA fragmentation in BECs did not necessarily represent apoptosis. UDCA showed a potential effect of reducing nuclear DNA fragmentation in BECs.

Apoptosis↗
PubMed1997

Insulin resistance is related to silent cerebral infarction in patients with essential hypertension.

Recently, hyperinsulinemia or insulin resistance has been suggested to be a risk factor for cardiovascular diseases. We evaluated the role of insulin resistance in the occurrence of silent cerebral infarction in 28 patients with essential hypertension (40 to 75 years, 157 +/- 4/89 +/- 2 mm Hg). Patients with diabetes mellitus or obesity (BMI > or = 30) were excluded. Insulin resistance was evaluated by means of constant glucose infusion rate (M value) during euglycemic-hyperinsulinemic glucose clamp test. Infarction was defined as a focal area with prolonged T1 and T2 relaxation times that was > 5 mm in diameter on brain magnetic resonance imaging. The severity of periventricular hyperlucency was evaluated by the distribution of the high intensity area. The number of silent infarctions significantly correlated only with the M value (F = 7.58, R2 = 0.23, P = .01) in multiple regression analysis using all variables: age, blood pressure, smoking history, lipid profile, levels of plasma glucose and insulin on fasting, and total amounts during 75-g OGTT. However, the severity of periventricular hyperlucency did not show a correlation with any factors. The occurrence of cerebral infarction was significantly correlated with thickening of the intima-media complex (IMC) of the common carotid artery on B-mode ultrasonography (F = 8.43, R2 = 0.25, P < .01). In conclusion, insulin resistance and thickening of IMC show a close relationship with the occurrence of silent cerebral infarction. Therefore, it may be important to improve insulin resistance for prevention of cerebral infarction in essential hypertensives.

Carotid Arteries↗
PubMed1997

Polymorphism of angiotensin converting enzyme, angiotensinogen, and apolipoprotein E genes in a Japanese population with cerebrovascular disease.

The homozygous deletion allele of the angiotensin converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the epsilon4 allele of the apolipoprotein E gene (apoE/epsilon4) are reported to be associated with ischemic heart disease. Cerebrovascular disease (CVD) is another atherosclerotic disease; and the effects of these polymorphisms on CVD have been confusing. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon4 genotypes are associated with CVD and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with cerebral infarction (n = 55) and cerebral hemorrhage (n = 38), diagnosed by brain computed tomography. Control subjects for the infarction group and the hemorrhage group were randomly selected from 583 subjects matched for age, gender, and history of hypertension with patients. Frequency of ACE/DD genotype was higher in the patients with infarction than in the controls (chi2 = 6.1, P < .05). The AGN/TT genotype was not associated with either infarction or hemorrhage, but it increased the relative risk for cerebral infarction in the subjects with ACE/DD genotype (chi2 = 8.0, P < .01, odds ratio; 11.7, 95% confidence intervals: 1.4 to 96.0). There was no significant association between apoE/epsilon4 and CVD. These results suggest that ACE/DD predicts cerebral infarction, but not cerebral hemorrhage, and that AGN/TT enhances the risk for cerebral infarction associated with ACE/DD.

Adult↗
PubMed1997

Establishment and characterisation of an osteoblastic clonal cell line from human mandibular osteosarcoma (HMOS-1).

A human mandibular osteosarcoma cell line, HMOS-1, with osteoblastic phenotypes and tumor-genicity was established. The cell line showed high alkaline phosphatase (ALP) activity immediately after seeding, with its peak around the 7th to 10th day of culture (1.44 mumol/min/mg protein). Parathyroid hormone (PTH) enhanced the ALP activity as well as intracellular cAMP production in a concentration-dependent manner. The effects of PTH on both ALP activity and cAMP production were expressed more strongly at the end stage of logarithmic cell growth than at the resting stage. 1,25 (OH)2D3 also stimulated the ALP activity, but its effect was low and was not different in any of the different culture stages. When these cells were transplanted to BALB/C nude mice, similar tumours to the original one, with abundant osteoids were observed. However, th e synthesis of type 1 collagen was not detected in the culture medium. The results indicate that the HMOS-1 cell line expresses an immature pre-osteoblastic phenotype. Because of these characteristics, HMOS-1 cells should be useful, not only in studies on the differentiated phenotypes of human osteoblasts, but also in studies on the diagnosis, treatment and aetiology of human osteosarcoma of the jaw.

Adult↗