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Biomedical subjects

H Masaki

Publications and source records attributed to H Masaki.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Importance of a cleaning in upper airways by using povidone iodine for the prevention of nosocomial pneumonia].

We investigated the efficacy of infection control measures against nosocomial pneumonia in geriatric wards. Cases with nosocomial pneumonia were retrospectively analyzed between January 1991 and March 1995. The study period was divided into four annual periods (periods 1, 2, 3 and 4). Period 1, January to December 1991, was applied as the cotrol. We investigated patients with nosocomial pneumonias in geriatric wards (190 beds) of AINO Memorial Hospital, affiliated with Nagasaki University. During the study period, nosocomial pneumonia significantly diminished. (period 1 vs periods 2, 3 and 4, p < 0.05, p < 0.05, p < 0.05, respectively). Major causative organisms of nosocomial pneumonia were MRSA and Pseudomonas aeruginosa. During the four periods, a significant reduction in cases with MRSA- and P. aeruginosa-induced nosocomial pneumonia was observed (MRSA: period 1 vs periods 2, 3 and 4, p < 0.05, p < 0.05, p < 0.01, respectively; P. aeruginosa: period 1 vs period 3, p < 0.01, period 2 vs periods 3 and 4, p < 0.01, p < 0.05, respectively). On the other hand, the improvement of decubitus ulcers was associated with a significant reduction in nosocomial pneumonia (period 1 vs. periods 2 and 3, p < 0.05 and p < 0.05, respectively). In conclusion, stringent infection control programs, including a cleaning in the upper airways by povidone iodine, are necessary in geriatric wards to reduce and prevent nosocomial pneumonia.

Aged↗
PubMed2001

Low concentrations of mupirocin in the pharynx following intranasal application may contribute to mupirocin resistance in methicillin-resistant Staphylococcus aureus.

We describe a patient with methicillin-resistant Staphylococcus aureus (MRSA) colonizing the pharynx. The MIC of mupirocin was 0.25 microg/ml before treatment and increased after treatment to 8 microg/ml. Using pulsed-field gel electrophoresis, we confirmed that the genotypes of MRSA that colonized the pharynx before and after the use of mupirocin were identical. We measured the delivery of mupirocin to the pharynx in three normal volunteers and two patients. Low concentrations of mupirocin were present in the pharynx in all cases 10 min to 3 days after intranasal application. Our data suggested that low concentrations of the drug in the pharynx after intranasal application of mupirocin ointment might explain the selection of mupirocin resistance in MRSA.

Aged↗
PubMed2001

Apoptosis is not increased in myocardium overexpressing type 2 angiotensin II receptor in transgenic mice.

To determine whether angiotensin type 2 (AT(2)) receptor stimulation induces apoptosis in cardiomyocytes in vivo, we developed transgenic mice overexpressing the AT(2) receptor in a cardiac-specific manner, using the alpha-myosin heavy-chain promoter. Ten- to 12-week-old male homozygous transgenic mice (n=44) and wild-type mice (n=44) were used. Both transgenic and wild-type mice were given either saline (control), a subpressor dose of angiotensin II (100 ng. kg(-1). min(-1)), a pressor dose of angiotensin II (1000 ng. kg(-1). min(-1)) for 14 days, a pressor dose of angiotensin II for 28 days to investigate the effects of stimulation on both angiotensin type 1 (AT(1)) and AT(2) receptors, the AT(1) antagonist L158809 alone, or a combination of angiotensin II (1000 ng. kg(-1). min(-1)) and L158809 for 14 days to investigate the effects of selective AT(2) receptor stimulation. Apoptosis was analyzed in paraffin-embedded ventricular sections by the terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) technique. In both transgenic and wild-type mice, administration of a subpressor dose of angiotensin II, L158809, or a combination of angiotensin II and L158809 did not significantly affect the tail-cuff blood pressure or heart-to-body weight ratio, whereas administration of a pressor dose of angiotensin II for 14 or 28 days significantly increased blood pressure and the heart-to-body weight ratio. However, there was no statistical difference between the effects of angiotensin II in transgenic and wild-type mice. The number of TUNEL-positive nuclei was approximately 0 to 10 per 100 000 cardiomyocytes, with no difference between transgenic and wild-type mice, regardless of saline infusion or any stimulation. In infarcted canine myocardial tissue sections for positive control, the number of TUNEL-positive nuclei was increased by 13.8 to 19.1 times compared with those in the noninfarcted myocardium. In conclusion, angiotensin II infusion for a period of 28 days failed to induce cardiomyocyte apoptosis regardless of the presence or absence of cardiac AT(2) receptor overexpression. It is unlikely that in mice the AT(2) receptor is a strong signal to induce cardiomyocyte apoptosis in vivo.

Angiotensin II↗
PubMed2001

Angiotensin II type 2 receptor inhibits epidermal growth factor receptor transactivation by increasing association of SHP-1 tyrosine phosphatase.

Angiotensin (Ang) II has 2 major receptor isoforms, Ang type 1 (AT(1)) and Ang type (AT(2)). AT(1) transphosphorylates epidermal growth factor receptor (EGFR) to activate extracellular signal-regulated kinase (ERK). Although AT(2) was shown to inactivate ERK, the action of AT(2) on EGFR activation remains undefined. Using AT(2)-overexpressing vascular smooth muscle cells from AT(2) transgenic mice, we studied these undefined actions of AT(2). Maximal ERK activity induced by Ang II was increased 1.9- and 2.2-fold by AT(2) inhibition, which was abolished by orthovanadate but not okadaic acid or pertussis toxin. AT(2) inhibited AT(1)-mediated EGFR tyrosine phosphorylation by 63%. The activity of SHP-1 tyrosine phosphatase was significantly upregulated 1 minute after AT(2) stimulation and association of SHP-1 with EGFR was increased, whereas AT(2) failed to tyrosine phosphorylate SHP-1. Stable overexpression of SHP-1-dominant negative mutant completely abolished AT(2)-mediated inhibition of EGFR and ERK activation. AT(1)-mediated c-fos mRNA accumulation was attenuated by 48% by AT(2) stimulation. Induction of fibronectin gene containing an AP-1 responsive element in its 5'-flanking region was decreased by 37% after AT(2) stimulation, corresponding to the results of gel mobility assay with the AP-1 sequence of fibronectin as a probe. These findings suggested that AT(2) inhibits ERK activity by inducing SHP-1 activity, leading to decreases in AP-1 activity and AP-1-regulated gene expression, in which EGFR dephosphorylation plays an important role via association of SHP-1.

Angiotensin II↗
PubMed2001

Safety and availability of doxazosin in treating hypertensive patients with chronic renal failure.

Hypertension accelerates the progression of renal disease in patients with chronic renal failure. Doxazosin, an alpha1-antagonist, is an antihypertensive agent with a long half-life. In this study, 15 patients with chronic renal failure were treated only with doxazosin and diuretics for 6 months and their blood pressure, renal parameters and lipid profile were measured. The initial dose of doxazosin was 2 mg/day and it was titrated until blood pressure was normalized. The average dose was 5.6 mg/day. As expected, systolic and diastolic blood pressure were decreased with treatment (165/91 mmHg to 135/73 mmHg). The drop in blood pressure was associated with an increase in glomerular filtration and a decrease in plasma BUN and creatinine levels. Reduction in mean blood pressure and decrease in proteinuria had a significant positive correlation (r=0.048, p=0.007). Proteinuria was decreased from 1.8 mg/day to 1.3 mg/day with doxazosin treatment and triglycerides also decreased, while HDL-cholesterol was increased. No side effects were observed. These results indicate that doxazosin is an efficient depressor agent with renal protective actions and that higher doses of doxazosin can be safely given to patients with chronic renal failure.

Adrenergic alpha-Antagonists↗
PubMed2001

Significant reduction of methicillin-resistant Staphylococcus aureus bacteremia in geriatric wards after introduction of infection control measures against nosocomial infections.

OBJECTIVES: (1) To investigate the efficacy of infection control measures against methicillin-resistant Staphylococcus aureus (MRSA) bacteremias in geriatric wards. (2) To identify predisposing risk factors for MRSA bacteremia. METHODS: Cases with nosocomial bacteremias were retrospectively analyzed between January 1991 and March 1995. The study period was divided into four annual periods and the period 1, January to December 1991, was applied as the control. MATERIALS: We investigated patients with nosocomial bacteremias in geriatric wards (190 beds) of AINO Memorial Hospital, affiliated with Nagasaki University. RESULTS: A significant reduction in cases with MRSA-induced nosocomial bacteremia was observed after the introduction of a stringent infection control and prevention program (period 1 vs. periods 2, 3, and 4: p<0.00833, p<0.00167, and p<0.00167, respectively). The major source of bacteremia included urinary tract infections, intravenous catheter-related infections, and infected decubitus ulcers. Improvement of decubitus ulcer was associated with a significant reduction in MRSA bacteremia (period 1 vs. periods 2 and 3: p<0.00017 and p<0.00833). CONCLUSION: Stringent infection control programs, including prevention and treatment of decubitus ulcers, are necessary in geriatric wards to reduce and prevent MRSA bacteremia.

Aged↗
PubMed2001

[Gene-therapy for peripheral vascular diseases].

The prognosis for patients with chronic critical leg ischemic is often poor. The treatment of peripheral vascular disease, although greatly improved over recent decades by drug medication, surgical and minimally-invasive techniques, remains limited by vascular proliferative lesions and by our inability to modulate the progression of native disease. The therapeutic angiogenesis is now the most expected therapy for peripheral vascular diseases. This review explores some of concepts and methods of therapeutic angiogenesis including gene therapy using angiogenic growth factor such as VEGF and basic FGF and an implantation of bone marrow derived endothelial progenitor cells.

Animals↗
PubMed2001

[Pathophysiology of blood pressure variability in patients with chronic renal failure under maintenance hemodialysis].

The rise of blood pressure is negatively related with the glomerullar filtration rate(GFR) in patients with terminal renal failure. Hypertension may be a mechanism to maintain renal blood flow and GFR constant by the increased driving force of blood to the kidney. Elevated levels of a so-called third factor, now designated as endogenous digitalis, are found in those patients. The most likely candidate of the endogenous digitalis is ouabain, which causes hypertension with chronic administration. On the other hand, extreme hypotension often occurs during maintenance hemodialysis, and since hemodynamic alterations closely resemble endotoxin shock, the involvement of nitric oxide(NO) over-production has been suggested. When we measured nitrate anion as the final metabolite of NO, the concentration was significantly higher in patients with marked hypotension during hemodialysis than those without hypotension. Since reflex tachycardia was not observed during hypotension, we speculated that those patients had autonomic disturbances, and assessed autonomic function by heart rate spectral analysis. Although the high frequency spectral power, regarded as the vagal tone, was not significantly different between the groups, low/high frequency spectral power ratio, which was thought to be a sympathetic component, was significantly lower in patients with hypotension during hemodialysis than that in patients without hypotension. We speculated that NO synthase may be induced by the stimuli to monocytes by tubes and dialyser membrane made of synthetic materials leading to the over production of NO during and after regular hemodialysis. Thus, cytokines may be the mediator of the induction of NO synthase. Dilated capacitance vessels decrease the venous return to the heart, which may be the direct cause of dialysis-induced hypotension.

Autonomic Nervous System↗
PubMed2001

[A case of primary racemose hemangioma of bronchial artery with recurrent hemoptysis].

A 42-year old man was admitted to our hospital because of hemoptysis. Bronchial arteriography revealed a tortuous and dilated left bronchial artery with a shunt formation between the bronchial and pulmonary arteries. Bronchial artery embolization using a sponge was performed three times to treat the hemoptysis, but all attempts failed. The patient therefore underwent left lower lobectomy, after which no hemoptysis was observed. Histopathologically, the resected tissue showed no inflammatory change. Interestingly, abnormal vessels resembling arteriovenous malformations were also found. Although the embolization therapy was effective in several reported cases, we concluded that surgery was required for this patient with persistent hemoptysis because of the development of collaterals and a bronchial-pulmonary artery shunt.

Adult↗
PubMed2001

Clinical evaluation of the Elecsys beta-CrossLaps serum assay, a new assay for degradation products of type I collagen C-tlopeptides.

BACKGROUND: The Elecsys beta-CrossLaps serum assay measures type I collagen degradation fragments (beta-CTx) that contain the beta-isomerized octapeptide EKAHD-beta-GGR. We investigated the analytical performance of the assay and changes in beta-CrossLaps in patients with metabolic bone diseases. METHODS: The electrochemiluminescent sandwich immunoassay uses two monoclonal antibodies directed against different regions of the linear EKAHD-beta-GGR. RESULTS: beta-CrossLaps (beta-CTx) immunoreactivity was stable in serum and plasma stored at 4 degrees C for 24 h or at room temperature for 4 h, and it did not decrease appreciably in samples stored at -30 degrees C for 12 weeks. Nine cycles of repeated freezing-thawing did not affect serum beta-CTx. The intra- and interassay imprecision (CVs) for four samples was < or = 2.6% (n = 10) and < or = 4.1% (n = 10), respectively. The mean day-to-day biological variation (CV) was 20% in 10 postmenopausal women (n = 10 days). Serum beta-CTx and osteocalcin were correlated in patients with hyperparathyroidism (r = 0.796; P <0.0001; n = 28), chronic renal failure on hemodialysis (r = 0.784; P = 0.0003; n = 16), hypoparathyroidism (r = 0.950; P = 0.0001; n = 11), and pseudohypoparathyroidism (r = 0.987; P = 0.130; n = 4). Serum beta-CTx decreased by 47.4% +/- 8.8% (mean +/- SD) and 60.7% +/- 6.5% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy in 34 women. These decreases were greater than the decreases in urinary excretion of deoxypyridinoline (31.8% +/- 3.9% and 38.1% +/- 4.4%, respectively) or pyridinoline cross-linked C-terminal telopeptide of type I collagen (15.9% +/- 3.9% and 16.9% +/- 4.6%, respectively). CONCLUSIONS: The Elecsys beta-CrossLaps serum assay provides a potentially useful tool for assessing bone resorption state, including its response to estrogen replacement therapy.

Biomarkers↗
PubMed2001

[Calcium supplement and bone metabolism].

Calcium supplementation ameliorates the elevated bone metabolism, especially for the elderly osteoporotic patients, because, calcium suppresses PTH level through the increase of serum calcium level. Urinary deoxypyridinolin, and/or NTx can detect the metabolic changes induced by calcium supplementation. Serum markers such as serum CTx or NTx will detect the small changes more clearly in near future.

English Abstract↗
PubMed2000

Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Rac1-mediated c-Jun NH2-terminal kinase.

Ca(2+)-sensitive tyrosine kinase Pyk2 was shown to be involved in angiotensin (Ang) II-mediated activation of extracellular signal-regulated kinase (ERK) via transactivation of epidermal growth factor receptor (EGF-R). In this study, we tested the involvement of Pyk2 and EGF-R in Ang II-induced activation of JNK and c-Jun in cardiac fibroblasts. Ang II markedly stimulated JNK activities, which were abolished by genistein and intracellular Ca(2+) chelators but partially by protein kinase C depletion. Inhibition of EGF-R did not affect Pyk2 and JNK activation by Ang II. Stable transfection with a dominant negative (DN) mutant for Pyk2 (PKM) completely blocked JNK activation by Ang II. DN mutants of Rac1 (DN-Rac1) and MEK kinase (DN-MEKK1) also abolished it, whereas those of Cdc42, RhoA, and Ha-Ras had no effect. Induction of c-Jun gene transcription by Ang II was abolished in PKM, DN-Rac1, and DN-MEKK1, in which Ang II-induced binding of ATF2/c-Jun heterodimer to the activator protein-1 sequence at -190 played a key role. These results suggest that 1) in cardiac fibroblasts activation of JNK and c-Jun by Ang II is initiated by Pyk2-dependent signalings but not by downstream signals of EGF-R or Ras, 2) Rac1 but not Cdc42 is required for JNK activation by Ang II upstream of MEKK1, and 3) ATF-2/c-Jun binding to the activator protein-1 sequence at -190 plays a key role for induction of c-Jun gene by Ang II.

Angiotensin II↗
PubMed2000

A cytotoxic ribonuclease which specifically cleaves four isoaccepting arginine tRNAs at their anticodon loops.

Colicin D has long been thought to stop protein synthesis in infected Escherichia coli cells by inactivating ribosomes, just like colicin E3. Here, we show that colicin D specifically cleaves tRNAs(Arg) including four isoaccepting molecules both in vivo and in vitro. The cleavage occurs in vitro between positions 38 and 39 in an anticodon loop with a 2',3'-cyclic phosphate end, and is inhibited by a specific immunity protein. Consistent with the cleavage of tRNAs(Arg), the RNA fraction of colicin-treated cells significantly reduced the amino acid-accepting activity only for arginine. Furthermore, we generated a single mutation of histidine in the C-terminal possible catalytic domain, which caused the loss of the killing activity in vivo together with the tRNA(Arg)-cleaving activity both in vivo and in vitro. These findings show that colicin D directly cleaves cytoplasmic tRNAs(Arg), which leads to impairment of protein synthesis and cell death. Recently, we found that colicin E5 stops protein synthesis by cleaving the anticodons of specific tRNAs for Tyr, His, Asn, and Asp. Despite these apparently similar actions on tRNAs and cells, colicins D and E5 not only exhibit no sequence homology but also have different molecular mechanisms as to both substrate recognition and catalytic reaction.

Anticodon↗
PubMed2000

Definition of an epitope on Japanese encephalitis virus (JEV) envelope protein recognized by JEV-specific murine CD8+ cytotoxic T lymphocytes.

We defined an epitope on the Japanese encephalitis virus (JEV) envelope (E) protein recognized by CD8+ cytotoxic T lymphocytes (CTLs). CTLs induced in JEV-infected BALB/c (H-2d) mice recognized E and/or premembrane (PrM) proteins, while CTLs in C57BL/6J (H-2b) and C3H/HeJ (H-2k) mice did not. JEV-specific CTLs had a phenotype of CD3+ CD4- CD8+. Twenty-four 9-amino acid (a.a.) peptides, which had binding motifs for H-2Kd, H-2Ld or H-2Dd, were synthesized according to the amino acid sequences of PrM and E proteins. CTLs induced by JEV infection recognized only the peptide K-3. Immunization of BALB/c mice with only a group of peptides including K-3 induced CTLs which recognized the homologous K-3 peptide, while immunization with other peptides did not. The peptide K-3 had a binding motif for H-2Kd. This is consistent with the finding that JEV-specific CTLs in BALB/c mice was H-2Kd-restricted. These results indicate that the epitope recognized by CTLs in BALB/c mice is located between a.a. 60 and 68 on the E protein, corresponding to an a.a. sequence of CYHASVTDI.

Amino Acid Sequence↗
PubMed2000

Transactivation of EGF receptor induced by angiotensin II regulates fibronectin and TGF-beta gene expression via transcriptional and post-transcriptional mechanisms.

The signaling cascade elicited by angiotensin II (Ang II) resembles that characteristic of growth factor, and recent evidence indicates transactivation of epidermal growth factor receptor (EGF-R) by G protein-coupled receptors. Here, we report the involvement of EGF-R in Ang II-induced synthesis of fibronectin and TGF-beta in cardiac fibroblasts. Ang II stimulated fibronectin mRNA levels dose-dependently with a maximal increase (approximately 5-fold) observed after 12 h of incubation. Ang II-, or calcium ionophore-induced fibronectin synthesis was completely abolished by tyrosine kinase inhibitors and intracellular Ca2+ chelating agents. Ang II-induced fibronectin mRNA was not affected by PKC inhibitors or PKC depletion, whereas specific inhibition of EGF-R function by a dominant negative EGF-R mutant and tyrphostin AG1478 abolished induction of fibronectin mRNA. We isolated the rat fibronectin gene including the 5'-flanking region and found that the AP-1 binding site present in the promoter region was responsible for the Ang II responsiveness of this gene. Gel retardation assay revealed the binding of nuclear protein to the AP-1 site, which was supershifted with anti-c-fos and anti-c-jun but not anti-ATF-2 antibodies. Conditioned medium from Ang II-treated cells contained TGF-beta bioactivity and addition of neutralizing TGF-beta antibody modestly (46%) inhibited induction of fibronectin. Ang II-induced synthesis of TGF-beta was also abolished by inhibition of EGF-R function. The effect of TGF-beta was exerted by stabilizing fibronectin mRNA without affecting the promoter activity and required de novo protein synthesis. We concluded that Ang II-induced expression of fibronectin and TGF-beta is mediated by downstream signaling of EGF-R transactivated by Ca2+-dependent tyrosine kinase, and that Ang II-induced fibronectin mRNA expression is regulated by two different mechanisms; transcriptional control by binding of c-fos/c-jun complex to the AP-1 site, and post-transcriptional control by mRNA stabilization due to autocrine and/or paracrine effects of TGF-beta. Thus, this study suggested that the action of Ang II on extracellular matrix formation should be interpreted in association with the EGF-R signaling cascade.

Angiotensin II↗
PubMed2000

Changes in patterns of left ventricular hypertrophy after aortic valve replacement for aortic stenosis and regurgitation with St. Jude Medical cardiac valves.

In this study, we analyzed the extent and pattern of regression of left ventricular (LV) hypertrophy after aortic valve replacement in patients with aortic stenosis (AS) and compared the results with those of another group of patients with aortic regurgitation (AR). Seventy patients who underwent isolated aortic valve replacement were divided into 2 groups. Group 1 was comprised of 29 patients who underwent aortic valve replacement for aortic stenosis, and Group 2 of 41 patients who underwent aortic valve replacement for aortic regurgitation. A third group of 10 healthy subjects served as a healthy control group. Echocardiographic studies were done before the operation and 5 years postoperatively. At follow-up, a significant reduction in the left ventricular mass was found in both groups, but it remained significantly greater than in the healthy control group. The ratio of LV wall thickness to radius (th/r) in Group 1 decreased significantly, and at follow-up it was within the normal value. In Group 2, the th/r ratio increased, and at follow-up it was within the normal value. After aortic valve replacement, the wall thickness remained significantly greater than normal for patients with AS, and the chamber radius remained significantly greater than normal for patients with AR. For these reasons, LV hypertrophy still existed in both groups at postoperative follow-up. The actuarial survival rate was 85.3% at 16 years for Group 1 and 83.4% at 18 years for Group 2. There was no significant difference in the long-term survival rates between the 2 groups. Actuarial freedom from valve-related events was 91.9% at 16 years for Group 1 and 82% at 18 years for Group 2. There was no significant difference in the valve-related event free curves between groups. After 5 years of follow-up, th/r reached normal for both groups, indicating remodeling of the LV geometry after aortic valve replacement.

Adult↗