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Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Nitric oxide inhalation and nitric oxide synthase inhibitor supplement for endotoxin-induced hypotension.

BACKGROUND: This study was performed to determine whether a combined therapy of nitric oxide (NO) inhalation and nitric oxide synthase (NOS) inhibitor is effective in experimental animals with endotoxin-induced refractive hypotension accompanied by pulmonary hypertension. METHODS: Escherichia coli lipopolysaccharide (1 mg/kg) was administered to 10 newborn piglets to induce endotoxemia. The experiment then began 60 min later, when the systemic arterial pressure dropped. The inhalation of 20 p.p.m. NO at 60 and 120 min of endotoxemia created a control group. Another group was also administered N w-nitro-L-arginine (L-NNA; 5 mg) after the first NO inhalation at 60 min of endotoxemia (the L-NNA group). Pulmonary arterial pressure, systemic arterial pressure and cardiac output were measured and compared among the groups. RESULTS: Three of the 5 piglets in the control group died of hypotensive shock, while in the L-NNA group the systemic arterial pressure recovered to pre-endotoxin administration levels. The L-NNA group produced a further increase in pulmonary arterial pressure against which NO inhalation was effective. CONCLUSION: Nitric oxide inhalation alone carries a potential risk of further lowering systemic arterial pressure in a piglet with hypotension induced by endotoxin, whereas the combined therapy resulted in the recovery of the blood pressure to pre-endotoxin levels. The combined therapy was simultaneously effective against pulmonary hypertension.

Animals↗
PubMed2001

Maintenance of oxidative phosphorylation protects cells from Actinobacillus actinomycetemcomitans leukotoxin-induced apoptosis.

Subnanomolar concentrations (3 x 10(-10) M) of Actinobacillus actinomycetemcomitans leukotoxin (Ltx) trigger apoptosis of JY cells, as shown by a decrease in mitochondrial transmembrane potential (DeltaPsim), hyperproduction of reactive oxygen species (ROS) and release of cytochrome c from the intermembrane space. When compared with heat-inactivated leukotoxin (DeltaI Ltx) controls, ATP levels in Ltx-treated JY cells continued to decrease during a 24 h experiment while cytoplasmic ADP concentrations were increasing. These results suggest that a blockage occurred in ATP/ADP exchange. To maintain ATP/ADP exchange, JY cells were transfected with bcl-2 and bcl-xL and incubated with Ltx. ATP levels of the transfected cells decreased to 67% (JY/bcl-2) and 73% (JY/bcl-xL) after the experiment. Furthermore, cytochrome c remained localized to the mitochondrial fraction of Ltx-treated JY/bcl-2 and JY/bcl-xL cells, whereas its presence in the cytoplasmic fraction of JY/gen cells suggests an uncoupling of electron transport. Expression of bcl-2 and bcl-xL in cells inhibited downstream apoptotic events such as cleavage of poly(ADP-ribose) polymerase, DNA fragmentation and activation of a family of caspases. The results indicate that Ltx induces apoptosis through a mitochondrial pathway that involves decreased levels of the ADP in the mitochondrial matrix, a lack of substrate for ATP synthetase and arrest of oxidative phosphorylation.

Adenosine Triphosphate↗
PubMed2001

Nrf2-deficient female mice develop lupus-like autoimmune nephritis.

BACKGROUND: NF-E2-related factor 2 (Nrf2) is a basic leucine zipper transcriptional activator essential for the coordinate transcriptional induction of antioxidant enzymes and phase II drug metabolizing enzymes through the antioxidant response element/electrophile response element. The Nrf2-deficient mice were found to develop normally under standard laboratory conditions. However, upon closer examination, we found that aged female Nrf2-deficient mice displayed a shortened lifespan and developed severe glomerulonephritis. The present study investigated the glomerulonephritis findings in Nrf2-deficient mice. METHODS: To evaluate glomerular lesions of Nrf2-deficient mice, histological and functional analyses were performed. The amounts of serum immunoglobulins, anti-double-stranded (ds) DNA antibody, and lipid peroxidation using thiobarbituric acid reactive substances (TBARS) also were measured. RESULTS: Nrf2-deficient female mice over 60 weeks of age developed severe nephritis characterized by cellular proliferation, lobular formation, crescent formation, and subepithelial electron-dense deposits. In immunofluorescent assays, Nrf2-deficient female mice showed mesangial deposits and massive granular deposits of IgG, IgM, and C3 along the capillary walls. Higher serum levels of IgG, anti-dsDNA antibody, lower creatinine clearance, and slight splenomegaly also were found in Nrf2-deficient female mice. A higher concentration of TBARS also was found in Nrf2-deficient female mice. CONCLUSIONS: These data indicate that the aged Nrf2-deficient female mice develop lupus-like autoimmune nephritis and suggest that nrf2 is one of the genes determining susceptibility to autoimmune disease. Analysis of nephritis in the Nrf2-deficient female mouse may clarify the mechanisms leading to the development of lupus disease.

Animals↗
PubMed2001

Infantile cholestatic jaundice associated with adult-onset type II citrullinemia.

Adult-onset type II citrullinemia, characterized by a liver-specific argininosuccinate synthetase deficiency, is caused by a deficiency of citrin that is encoded by the SLC25A13 gene. Three patients with infantile cholestatic jaundice were found to have mutations of the SLC25A13 gene. Adult-onset type II citrullinemia may be associated with infantile cholestatic disease.

Biopsy↗
PubMed2001

Transient involvement of endothelin in hypertrophic remodeling of small arteries.

OBJECTIVE: This study was designed to evaluate the capacity of norepinephrine (NE) to induce hypertrophic remodeling of small arteries in rats, and to determine the involvement of endothelin (ET) to initiate and maintain it. DESIGN AND RESULTS: Treatment with NE (2.5 microg/kg per min) for 14 or 28 days produced a similar inward hypertrophic remodeling, characterized by a smaller lumen, but increased media thickness and cross-sectional area. Arterial stiffness was reduced. Histological evaluation confirmed the hypertrophic nature of remodeling. Concomitant administration of LU135252 (ET-receptor antagonist) for the first 14 days of NE administration prevented the development of hypertrophy, without altering arterial mechanics. Treatment with the same antagonist from day 14 to day 28 of NE or angiotensin II (Ang II) treatment failed to regress established vascular hypertrophy. In contrast, normalization of arterial structure was observed with prazosin, an alpha-adrenergic blocker. Endothelin content in small mesenteric arteries showed a transient elevation following chronic NE administration. CONCLUSIONS: Increased circulating NE levels are associated with hypertrophic remodeling of small arteries, in which ET plays an initiating role. However, the maintenance of vascular hypertrophy is ET-independent, either in the presence of augmented circulating levels of NE or Ang II. Thus, early rather than late treatment with ET-receptor antagonists may be a preferable approach to limit small artery-mediated end-organ damage in cardiovascular diseases.

Angiotensin II↗
PubMed2001

Beneficial effect of muscarinic-2 antagonist on dilated cardiomyopathy induced by autoimmune mechanism against muscarinic-2 receptor.

We have previously shown that a peptide corresponding to the sequence of the second extracellular loop of the human muscarinic-2 (M2) receptor (M2-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we investigated the effect of M2-antagonist (otenzepad) on M2-peptide-induced cardiomyopathy in rabbits. New Zealand White rabbits were divided into four groups: 1) control group, saline injection; 2) M2-peptide group, M2-peptide injection; 3) M2-antagonist group, otenzepad (30 mg/day) orally and saline injection; and (4) M2-antagonist + M2-peptide group, otenzepad (30 mg/day) orally and M2-peptide injection. The study duration was 1 year. Saline or peptide was injected once a month. All rabbits in both the M2-peptide group and the M2-antagonist + M2-peptide group had high titers of anti-M2-autoantibodies in their sera. Rabbits in the M2-peptide group showed an increase in heart weight, wall thinning and dilatation of the right ventricle. On the contrary, rabbits in the M2-antagonist + M2-peptide group had normal heart weight and shape. All rabbits in the M2-peptide group showed multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells, while four rabbits in the M2-antagonist + M2-peptide group showed slight infiltration of inflammatory cells with normal myocardial cells and interstitium, and another three showed no histological changes in the hearts. In conclusion, M2-antagonist protects the myocardium from injury induced by autoimmune mechanism against M2-muscarinic receptor.

Animals↗
PubMed2001

Unusual brain metastases from papillary thyroid carcinoma: case report.

OBJECTIVE AND IMPORTANCE: Brain metastases from papillary carcinoma of the thyroid gland are unusual. No consensus regarding management has yet been reached. We report a case, review the current literature, and explain our approach on the basis of clinical, pathological, and radiological data. CLINICAL PRESENTATION: A 33-year-old woman presented with signs of intracranial hypertension. The diagnostic evaluation included chest tomography, head computed tomography, brain magnetic resonance imaging with and without contrast enhancement, total-body scanning, and cerebral scintigraphy. Multiple supratentorial lesions and one right cerebellopontine angle lesion were observed. Histopathological analysis of the surgical specimen confirmed papillary carcinoma of the thyroid gland. INTERVENTION: A ventriculoperitoneal shunt was placed and a right suboccipital craniotomy was performed, with complete removal of the cerebellopontine angle tumor. Total-brain irradiation with 40 Gy/lesion followed the initial operation. One year after surgery, the patient presented with signs of increased intracranial pressure. A new left frontal lobe lesion with massive peritumoral edema was identified on magnetic resonance imaging scans. The edema was treated clinically and a left frontal craniotomy was performed, with complete resection of the tumor. The patient is currently faring well, with residual expressive aphasia. CONCLUSION: Surgery followed by radiotherapy seems to be a good alternative for the treatment of this specific type of metastasis. Thorough clinical and radiological evaluation, followed by genetic analysis of the surgical specimen, particularly with respect to the potential for tumor invasion under specific conditions, is recommended. The information obtained contributes to better management and better overall long-term outcomes for these patients.

Adult↗
PubMed2001

Increased plasminogen activator inhibitor-1 and apolipoprotein (a) in coronary atherectomy specimens in acute coronary syndromes.

BACKGROUND: Although increased tissue factor expression is known in vulnerable plaques, there is no reported study to compare plaque fibrinolysis in stable and unstable plaques. This study investigates the extent of plasminogen activator inhibitor-1 (PAI-1) and apolipoprotein (a) [apo(a)] in the plaques of different types of coronary artery disease as well as the correlation between these molecules and infiltration of macrophages to plaques. METHODS: Using immunohistochemical staining, we examined PAI-1 expression and apo(a) deposition in coronary atherosclerotic specimens obtained by directional coronary atherectomy from 19 patients with acute myocardial infarction (AMI), 12 with unstable angina pectoris (UAP), and 13 with stable angina pectoris (SAP). The percentages of the total areas of specimens stained with PAI-1 or apo(a) were estimated by an NIH image program. The proportion of macrophages as a percentage of all cells in plaques was calculated as the macrophage density. RESULTS: We found significantly higher percentages of total areas of specimens stained with PAI-1 in AMI (25.5 +/- 8.6%, P < 0.001) and UAP (22.2 +/- 10.4%, P < 0.005) than in SAP (9.5 +/- 5.0%), as well as with apo(a) (AMI; 11.7 +/- 7.1%, P < 0.005, UAP; 11.1 +/- 5.5%, P < 0.01 versus SAP; 3.9 +/- 1.5%). Linear regression analysis of all the samples showed a correlation between PAI-1 or apo(a) and macrophage density (PAI-1: r = 0.75, P < 0.001 and apo(a): r = 0.56, P < 0.001). CONCLUSIONS: Our results suggest a possible contribution of increased PAI-1 and apo(a) in plaques to the pathogenesis of acute coronary syndromes including impaired fibrinolysis.

Aged↗
PubMed2001

Troglitazone, a ligand for peroxisome proliferator-activated receptor gamma, inhibits chemically-induced aberrant crypt foci in rats.

The biological roles of peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, have been highlighted recently. Although PPARgamma ligand is suspected to play an important role in carcinogenesis, its effects on colon tumorigenesis remain undetermined. The present time-course study was conducted to investigate possible modifying effects of a PPARgamma ligand, troglitazone, on the development and growth of aberrant crypt foci (ACF), putative precursor lesions for colon carcinoma, induced by azoxymethane (AOM) or dextran sodium sulfate (DSS) in male F344 rats. Oral troglitazone (10 or 30 mg / kg body weight (b.w.)) significantly reduced AOM (two weekly subcutaneous injections, 20 mg / kg b.w.)-induced ACF. Treatment with troglitazone increased apoptosis and decreased polyamine content and ornithine decarboxylase (ODC) activity in the colonic mucosa of rats treated with AOM. Gastric gavage of troglitazone also inhibited colitis and ACF induced by DSS (1% in drinking water), in conjunction with increased apoptosis and reduced colonic mucosal polyamine level and ODC activity. Our results suggest that troglitazone, a synthetic PPARgamma ligand, can inhibit the early stage of colon tumorigenesis with or without colitis.

Animals↗
PubMed2001

Residue aspartate-147 from the third transmembrane region of Na(+)/H(+) antiporter NhaB of Vibrio alginolyticus plays a role in its activity.

NhaB is a bacterial Na(+)/H(+) antiporter with unique topology. The pH dependence of NhaB from Vibrio alginolyticus differs from that of the Escherichia coli NhaB homolog. Replacement of Asp-147 with Glu made high H(+) concentrations a requirement for the NhaB activity. Replacement of Asp-147 with neutral amino acids inactivated NhaB.

Amino Acid Substitution↗
PubMed2001

Role of PAC(1) receptor in adrenal catecholamine secretion induced by PACAP and VIP in vivo.

The present study was conducted to investigate the functional implication of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I (PAC(1)) receptor in the adrenal catecholamine (CA) secretion induced by either PACAP-27 or vasoactive intestinal polypeptide (VIP) in anesthetized dogs. PACAP-27, VIP, and their respective antagonists were locally infused to the left adrenal gland via the left adrenolumbar artery. Plasma CA concentrations in adrenal venous and aortic blood were determined by means of a high-performance liquid chromatograph coupled with an electrochemical detector. Adrenal venous blood flow was measured by gravimetry. The administration of PACAP-27 (50 ng) resulted in a significant increase in adrenal CA output. VIP (5 microg) also increased the basal CA secretion to an extent comparable to that observed with PACAP-27. In the presence of PACAP partial sequence 6--27 [PACAP-(6--27); a PAC(1) receptor antagonist] at the doses of 7.5 and 15 microg, the CA response to PACAP-27 was attenuated by approximately 50 and approximately 95%, respectively. Although the CA secretagogue effect of VIP was blocked by approximately 85% in the presence of PACAP-(6--27) (15 microg), it remained unaffected by VIP partial sequence 10--28 [VIP-(10--28); a VIP receptor antagonist] at the dose of 15 microg. Furthermore, the CA response to PACAP-27 did not change in the presence of the same dose of VIP--(10--28). The results indicate that PACAP-(6--27) diminished, in a dose-dependent manner, the increase in adrenal CA secretion induced by PACAP-27. The results also indicate that the CA response to either PACAP-27 or VIP was selectively inhibited by PACAP-(6--27) but not by VIP-(10--28). It is concluded that PAC(1) receptor is primarily involved in the CA secretion induced by both PACAP-27 and VIP in the canine adrenal medulla in vivo.

Adrenal Medulla↗
PubMed2001

Overexpression of the Csk homologous kinase (Chk tyrosine kinase) induces multinucleation: a possible role for chromosome-associated Chk in chromosome dynamics.

The Csk family of non-receptor-type tyrosine kinases consists of Csk and the Csk homologous kinase Chk. Each enzyme suppresses the catalytic activity of Src family kinases by phosphorylating their C-terminal negative regulatory tyrosine residues. Ectopic and transient expression of Chk in COS-1 cells showed nuclear localization of Chk and growth inhibition. To further explore the role of Chk in cell growth, we overexpressed Chk in human immature myeloid KMT-2 cells. Chk overexpression brought about growth retardation and aberrant chromosome movement leading to multinucleation, and these events were accompanied by insufficient formation of mitotic spindles. In vitro kinase assays showed that Chk overexpression suppressed the tyrosine kinase activity of Lyn, a member of the Src family, immunoprecipitated from Triton X-100 lysates. Subcellular fractionation studies revealed that fractions of Chk and Lyn, resistant to Triton X-100 solubilization, are associated with mitotic chromosome scaffolds and spindles. Chk overexpression induced a decrease in autophosphorylation of Lyn and concomitant changes in levels of tyrosine phosphorylation of proteins associated with both fractions. These results indicate that Chk, Lyn and the tyrosine-phosphorylated proteins localize to mitotic chromosomes and spindles, suggesting that Chk-dependent tyrosine phosphorylation, presumably through Lyn, may be involved in chromosome dynamics.

Animals↗
PubMed2001

[Persistent pulmonary hypertension of the newborn].

Persistent pulmonary hypertension of the newborn (PPHN) is a cardiopulmonary disorder characterized by systemic arterial hypoxemia secondary to elevated pulmonary vascular resistance with resultant shunting of pulmonary blood flow to the systemic circulation. This disorder can be classified into four forms dependent on the etiology of the pulmonary hypertension: (1) Hypoplastic lung associated with congenital diaphragmatic hernia and oligohydramnions. (2) Primary PPHN (without known causative factor), such as preterm PPHN. (3) Secondary PPHN (with known causative factor), such as meconium aspiration syndrome, birth asphyxia or respiratory distress syndrome. (4) Relative PPHN associated with heart failure of hydrops fetalis or ischemic myocardial dysfunction. Inhalation of nitric oxide, which previously known as endothelial-derived-relaxation-factor, has been studied intensively as therapy for PPHN.

Administration, Inhalation↗
PubMed2001

A new prognosis factor analysis based on nonhomogeneous Markov description.

To evaluate prognosis factors, Cox's proportional hazard model has been used. But it was found that the analytical ability was not sufficient. So we propose a new evaluation method combining Markov chain model and multiple logistic regression analysis to estimate the prognosis factors. Stage II breast cancer was chosen as the subject. The data was retrospective data gathered in National Cancer Center Central Hospital. As first step, a simple Markov chain model was constructed to describe the state transition of a breast cancer. Then the multiple property of each state transition was investigated in detail. And the patients who had gotten a recurrence for the first two and a half years were discriminated as the poor prognosis group by a nonparametric test (p < 0.05). And the result proved to corresponding with the clinical experience. As second step, three factors (n classification of pathological diagnosis, ductal spread, and estrogen receptor) were selected as the prognosis factors for the early death in Stage II breast cancer by a multiple logistic regression analysis. This new prognosis factor analysis could find out some scientific evidences. Especially, it was found to be remarkable efficient in proving clinically experienced observation.

Breast Neoplasms↗