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Biomedical subjects

H Yamaguchi

Publications and source records attributed to H Yamaguchi.

At least 559 records · Page 31Linked to original sources

Pressure-interval relationship characterizes left ventricular irregular beat contractilities and their mean level during atrial fibrillation.

How left ventricular (LV) contractility relates to irregular RR intervals during atrial fibrillation (AF) is still unclear. We investigated the relationship between the LV contractility (Emax) of individual beats and their preceding RR intervals during AF in isovolumic contractions is excised cross-circulated canine hearts, and additionally in ejecting contractions in in situ canine hearts. Atrial high-frequency electrical stimulation induced AF. We recorded a LV electrocardiogram, volume and pressure, and calculated the Emax of every arrhythmic beat. Multiple linear regression analysis between Emax and the six preceding RR intervals of all arrhythmic beats during 1 min AF showed the preceding RR interval (RR1) and the pre-preceding interval (RR2) to be the predominant predictors of Emax. The Emax-RR1/RR2 scattergram was closely fitted by a linear regression line. We found Emax at RR1/RR2 = 1 on the regression line to be virtually identical with both mean Emax during AF and stable Emax obtained during irregular atrial pacing at the same intervals as the mean RR interval during AF. These results newly indicate that the pressure-interval relationship predominantly characterizes LV irregular beat contractilities and their mean level during AF.

Animals↗

Excitatory amino acid receptors in the paraventricular hypothalamic nucleus mediate pressor response induced by carotid body chemoreceptor stimulation in rats.

In urethane-anesthetized rats with spinal transection, antagonists of excitatory amino acid receptors, P2 purinoceptors and adrenoceptors were microinjected into the paraventricular hypothalamic nucleus (PVN) and their effects on the pressor response evoked by carotid body chemoreceptor stimulation were examined. Microinjections of the non-selective excitatory amino acid antagonist kynurenate, the non-NMDA receptor antagonist CNQX and the NMDA antagonist 2-amino-5-phosphonovalerate (AP5) into the PVN inhibited the chemoreceptor reflex-induced pressor response. The excitatory amino acid agonist L-glutamate injected into the PVN produced an increase in blood pressure. The P2 purinoceptor antagonist suramin did not affect the pressor response and ATP did not affect basal blood pressure. The alpha adrenoceptor antagonist phentolamine, prazosin and yohimbine also inhibited the chemoreceptor-induced pressor response, while the beta antagonist propranolol did not affect it. These findings indicate that excitatory amino acid receptors and alpha adrenoceptors in the PVN are involved in mediating the pressor response induced by carotid body chemoreceptor stimulation in rats.

2-Amino-5-phosphonovalerate↗

Mode of antifungal action of benanomicin A in Saccharomyces cerevisiae.

The mechanism of fungitoxic action of an antifungal antibiotic benanomicin A was studied with intact cells and protoplasts of Saccharomyces cerevisiae as well as with its enzymic preparations. The results obtained are summarized as follows: (1) benanomicin A at relatively high concentrations (almost equal to MIC) was fungicidal and disrupted the cell permeability barrier, inducing leakage of intracellular K+ and ATP in growing cells, while the antibiotic had none of these effects in non-growing cells; (2) no biosynthesis of any of several major cellular constituents in yeast cells was inhibited markedly or selectively enough to explain its fungitoxic activity; (3) whereas benanomicin A induced lysis of metabolically active yeast protoplasts incubated in the presence of glucose, inactive yeast protoplasts incubated without glucose were refractory to the lytic action of the antibiotic; (4) osmotically shocked yeast cells became feasible to the cidal action of benanomicin A; (5) benanomicin A substantially inhibited uptake of 6-deoxy-glucose by yeast cells; (6) liposomes composed of phospholipids and cholesterol were not susceptible to benanomicin A; and (7) benanomicin A inhibited in vitro activity of H(+)-ATPase from yeast cell membranes to a greater extent than that for H(+)-ATPase from yeast mitochondria or H(+)-ATPase from yeast vacuolar membranes. Based on these and our previous data that benanomicin A preferentially binds to mannan or mannoproteins constituting the cell wall and cell membrane of yeasts, such binding of the antibiotic is suggested to deteriorate the normal structure and function of those cell membranes of yeasts which are in a growing or metabolically active state, ultimately leading to cell death.

Adenosine Triphosphatases↗

Increased plasma guanylin levels in patients with impaired renal function.

Guanylin, a 15-amino acid peptide, activates intestinal guanylate cyclase C receptor, thereby regulating intestinal fluid and electrolyte transport through the second messenger, cyclic GMP. To examine the role of the kidney in guanylin metabolism, we used a radioimmunoassay (RIA) to measure plasma concentrations of guanylin in 3 groups; normal individuals, patients who had renal disorders with normal or elevated serum creatinine levels (0.4 < Cre < 11.9 mg/dl), and patients who received hemodialysis (HD). The plasma concentration of immunoreactive guanylin in the normal individuals was 32.3 +/- 4.8 fmol/ml. The concentrations in 32 non-HD patients were correlated with their serum creatinine concentrations (r = 0.81, p < 0.0001). In 16 HD patients the plasma concentrations of immunoreactive guanylin before the start of HD were correlated with their dialysis duration (r = 0.63, p < 0.01). The plasma levels of immunoreactive guanylin in HD patients for whom EVAL membranes were used decreased one hour after the start of HD as compared with the prior levels. The plasma levels in HD patients for whom PC membranes were used showed no change. Ten kilodalton guanylin is the main component of guanylin molecules in the plasma and hemofiltrates of HD patients. These findings suggest that the kidney has a major role in the elimination and/or metabolism of guanylin. Uroguanylin, a member of the guanylin family that was recently isolated from human urine, also acts on the guanylate cyclase C receptor. Further studies of guanylin family peptides should provide a better understanding of the physiological roles of the kidney in the control of water and electrolyte balance.

Binding Sites↗

[Application of NGF/PC12 cell system for screening tubulin inhibitors].

Microtubules are stiff polymers that extend throughout the cytoplasm of eukaryotic cells and regulate the location of intracellular compartments. Microtubules are formed by the polymerization of tubulin molecules, each of which is a heterodimer consisting of two closely related globular polypeptides, alpha-tubulin and beta tubulin. Many of the microtubule arrays are labile and are turning over rapidly; they depolymerize and repolimerize continually in living cells. One of the most striking examples is the mitotic spindle, which forms after the cytoplasmic microtubules disassemble at the onset of mitosis. The mitotic spindle is the target of a variety of agents that act by interfering with the exchange of tubulin subunits between the microtubules and the free tubulin pool; some of these agents can be used as antimitotic or anticancer drugs. We recently have developed a simple and sensitive method of screening for tubulin inhibitors, to which we have successfully applied the nerve growth factor/PC12 cell system. In this report, we describe the details of this method for screening tubulin inhibitors, by which we have analyzed several well-known and new compounds a model experiments.

Animals↗

Juvenile systemic granulomatosis manifesting as premature aging syndrome and renal failure.

We describe a case of juvenile systemic granulomatosis in a 22-year-old woman. The rash consisted of purple papules and first appeared at the age of one year. She had persistent symmetrical painless boggy tenosynovitis with minimal roentgenographic changes and chronic granulomatous symptoms. Uveitis resulted in visual impairment. She also had granulomatous changes in her vessels. Renal impairment developed; however, neither renal artery stenosis nor hypercalcemia was found. Clinical features included the development of premature aging with alopecia, which differed from the previously reported progeria syndrome. Poikiloderma may cause a prematurely aged appearance. Our report expands the clinical spectrum of systemic granulomatosis to include the development of premature aging with alopecia.

Adult↗

[Genetic diagnosis of aspergillosis].

Aspergillosis is an opportunistic infection caused by pathogenic Aspergillus species (spp.) and is a major hazard for immunocompromised patients and even for non-immunocompromised individuals. Clinical diagnosis of aspergillosis, especially invasive pulmonary aspergillosis (IPA) is difficult and is largely presumptive, typically based on spiking fevers not responding to antibiotics in a patient with the risk factors. It is well known that Aspergillus spp. can be only infrequently cultured from clinical specimens, and that the cultural examination is laborious and time-consuming. Moreover, positive culture from bronchoalveolar lavage or sputa is indicative, but not proof of infection. The criterion for diagnosis of pulmonary infection by aspergilli requires repeated isolation of the same species of Aspergillus from respiratory specimens. There have been some successful attempts using serological assays to detect circulating antibodies to Aspergillus spp. in the noninvasive form of the disease, but these are generally negative in an acute phase IPA patient. A currently available serodiagnostic kit, Pastrex Aspergillus is limited in clinical usefulness because of low sensitivity and specificity in spite of being simple and rapid. Contamination of clinical specimens with various saprophytic filamentous fungi other than aspergilli also often give false positive. Diagnostic methods using such molecular biological techniques, as polymerase chain reaction (PCR) have recently been employed to identify DNA from a number of pathogens when diagnostic means are limited. PCR is known as the most sensitive and specific technique by which to detect a specific DNA sequence. In this paper we have reviewed new genetic methods of diagnosing aspergillosis including PCR and in situ hybridization.

Aspergillosis↗

[In vitro antifungal activity of rilopirox, a new hydroxypyridone antimycotic agent].

In vitro antifungal activities of rilopirox (RIL), a new topical hydroxypyridone antifungal agent, were studied against 7 species (31 strains) of yeast-like fungi and 15 species (17 strains) of mycerial fungi from stock cultures of a wide range of medically important fungi. Tests were carried out by the liquid dilution method using Neopeptone dextrose broth with ciclopirox olamine (CPO) and oxiconazole nitrate (OCZ) as reference drugs. RIL exhibited a broad spectrum of antifungal activities; the MIC of RIL against yeasts were about 1 microgram/ml, those against other fungi were 0.5-4 micrograms/ml. Antifungal activities were similar to CPO, and compare to OCZ, RIL showed characteristically little differences in its activities against different species or strains of target organisms.

Antifungal Agents↗

A novel missense mutation in the endoglin gene in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystem vascular dysplasia and recurrent hemorrhage. Recent investigation has mapped one of the responsible genes for HHT to chromosome 9q33-q34; subsequently, nine different mutations have been identified in the endoglin gene, which encodes a transforming growth factor beta (TGF-beta) binding protein, in nine unrelated families with HHT. We examined the endoglin gene in a Japanese patient with HHT and her family members. Using PCR-SSCP analysis followed by sequencing, we identified a C to A missense mutation in exon 4 which changed an Ala160 codon(GCT) to an Asp160 codon (GAT). Since this mutation destroys one of three Fnu4H 1 sites in exon 4, the Fnu4H I digestion patterns of the PCR-amplified exon 4 fragments from each family member were analyzed. In affected members, the restriction patterns were all consistent with a phenotype of HHT. PCR-amplified exon 4 fragments from 150 normal individuals were also analyzed by allele-specific oligonucleotide hybridization analysis. As a result, the mutation was not found in any of them. We conclude that the C to A mutation in exon 4 of the endoglin gene in this proband is responsible for the occurrence of HHT in this family.

Aged↗

[Percutaneous transluminal coronary angioplasty in patients with multivessel coronary disease: does complete revascularization improve the long-term survival?].

The influence of complete revascularization on long-term outcome of patients with multivessel coronary artery disease undergoing percutaneous transluminal coronary angioplasty (PTCA) was determined by analysis of 10-year survival in 167 consecutive patients treated at Juntendo University Hospital during 1984-1993. Forty-nine patients were completely revascularized and 118 had incomplete revascularization according to the anatomical classification. Among patients with anatomically incomplete revascularization, 56 were categorized as functionally adequate revascularization and 62 as functionally inadequate revascularization according to Faxon's criteria. Baseline characteristics showed incompletely revascularized patients had a higher incidence of prior myocardial infarction triple-vessel disease and/or chronic total occlusion in at least one lesion. The 10-year survival was slightly better in patients with complete (100%) than in those with incomplete revascularization (79%), but not statistically significant (p = 0.089). Event-free survival was not significantly different between the two groups. However, the need for coronary artery bypass surgery was higher in the incomplete revascularization group than that in the complete revascularization group (100% vs 81%, p = 0.013). The influence of the degree of functional revascularization on outcome was not clear in the present study. Long-term survival appeared to be better in patients with complete revascularization than that in patients with incomplete revascularization, but even in the latter, coronary artery bypass grafting in the later period could improve outcome. The effect of functional revascularization status should be further investigated in a larger population.

Angioplasty, Balloon, Coronary↗

[Concealed infective endocarditis].

The occurrence of concealed infection or "natural remission" in infective endocarditis was investigated microscopically in 35 consecutive patients (36 valves) with infective endocarditis (between April 1987 and May 1995). Four patients were considered as having concealed or silent infective endocarditis. Preoperative diagnosis of these patients was mitral valve prolapse, rheumatic aortic valve stenosis with insufficiency, aortic valve prolapse and hypertrophic cardiomyopathy, respectively. These patients did not present with any clinical signs of infective endocarditis such as cardiac murmur and ventricular dysfunction. Histological examination of the excised valves revealed valvular perforation, small round cell infiltration, neovascularization, remnants of vascular smooth muscle cells, and organizing vegetations. These findings are consistent with the histological findings of infective endocarditis. Latent infective endocarditis may be present without inflammatory manifestation.

Aortic Valve Insufficiency↗

Evaluation of plasma (1-->3)-beta-D-glucan measurement by the kinetic turbidimetric Limulus test, for the clinical diagnosis of mycotic infections.

The present multicentre clinical study was conducted to assess the clinical utility of a new diagnostic method for deep mycosis in which (1-->3)-beta-D-glucan, a fungal cell wall component existing in plasma, was quantitatively measured by the kinetic turbidimetric Limulus test (WB003). Plasma (1-->3)-beta-D-glucan concentrations were 0.57 +/- 0.10 microgram/l in 92 healthy subjects and 0.62 +/- 0.32 microgram/l in 26 patients with non-mycotic diseases (disease control group). In comparison with these healthy subjects and patients with non-mycotic diseases, patients with mycosis had significantly higher plasma (1-->3)-beta-D-glucan concentrations: 19.63 +/- 73.28 micrograms/l in 12 patients with candidaemia, 11.28 +/- 21.42 micrograms/l in 7 patients with urinary Candida infection, 4.84 +/- 12.71 micrograms/l in 5 patients with pulmonary candidiasis, and 12.21 +/- 31.31 micrograms/l in 4 patients with invasive pulmonary aspergillosis. On the statistical analysis of these data, a cut-off value was set at 1.0 microgram/l. Using this cut-off value, 3 patients with pulmonary cryptococcosis and 4 patients (4/6) with pulmonary aspergilloma were all negative with low plasma (1-->3-beta-D-glucan levels. The test WB003 provided equivalent or higher efficiency of diagnosis of candidiasis and aspergillosis, in comparison with commercially available antigen detection kits, demonstrating its utility as a diagnostic reagent. It may also be useful in assessing therapeutic effectiveness when used periodically after treatment.

Adolescent↗

[Transthoracic Doppler echocardiographic detection of intramyocardial coronary artery flow in humans using high frequency transducer].

The use of transthoracic color and pulsed Doppler echocardiography to detect intramyocardial coronary artery flow in humans was evaluated in 18 normal healthy subjects (mean age 54 years) and in 16 patients with hypertrophic cardiomyopathy (HCM; mean age 59 years) to measure the intramyocardial coronary artery flow velocity at the ventricular septum and the apex using a 10-5 or 7-4 MHz transducer. Linear inflow color Doppler signals which passed the interventricular septum were demonstrated in 15 of 18 normal subjects (83%) and 15 of 16 patients with HCM (94%). The phasic flow velocities measured by pulsed Doppler echocardiography consisted of two forward flow signals in mid-systole (S-wave) and holodiastole (D-wave), and were obtained in 11 of 18 in normal subjects (61%) and 14 of 16 patients with HCM (88%). The mean peak velocities of the S- and D-waves in patients with HCM (mean [+/-SD] 27 +/- 9 and 86 +/- 23 cm/sec, respectively) were significantly (p < 0.05) higher than those in normal subjects (18 +/- 4 and 54 +/- 11 cm/sec, respectively). At the apex, linear inflow color Doppler signals which passed the myocardium perpendicularly during the whole diastole were demonstrated in 14 of 18 normal subjects (78%) and all 16 patients with HCM (100%). The phasic flow velocities were measured by pulsed Doppler echocardiography in 10 of 18 normal subjects (56%) and 15 of 16 patients with HCM (94%). The mean peak velocities in patients with HCM (74 +/- 27 cm/sec) were significantly (p < 0.05) higher than those in normal subjects (33 +/- 13 cm/sec). Transthoracic color and pulsed Doppler echocardiography can detect intramyocardial coronary artery flow in humans at the interventricular septum and the apex noninvasively.

Blood Flow Velocity↗

Studies on the antifungal activity of the new imidazole antimycotic lanoconazole in infected sites. Distribution in the skin and in vitro activity in the presence of stratum corneum.

To answer the question why topically applied lanoconazole (CAS 101530-10-3, NND-318) is so highly effective in the treatment of dermatomycoses in both animal models and human patients, the antifungal activity of lanoconazole in infected sites was investigated. 1. Distribution of lanoconazole in rat skin: The distribution of lanoconazole within the dorsal skin of rats was examined by measurement of radioactivity and microscopic autoradiography. 24 h after dermal application of 14C-lanoconazole cream formulation, 83% of the total radioactivity in the skin was recovered from the stratum corneum, and thereafter the radioactivity decreased gradually up to 96 h. Metabolite analysis showed that more than 94% of the extractable radioactivity was lanoconazole itself after 24 and 48 h. Microautoradiograms of the skin also supported the radioactivity distribution. 2. In vitro antifungal activity in stratum corneum-containing medium: Candida albicans TIMM 2640 was incubated for 10 days at 27 degrees C in a vitamin-supplemented yeast carbon base medium containing 5 mg/ml of human stratum corneum and different concentrations of lanoconazole or bifonazole (CAS 60628-96-8, reference agent). Compared with the control culture, lanoconazole strongly inhibited fungal growth in a concentration dependent manner at concentration above 0.1 microgram/ml, resulting in a reduction of viable cell recovery to less than 50% after 10 days. The inhibitory activity of bifonazole was clearly weaker than that of lanoconazole. At concentrations of 0.1-10 micrograms/ml lanoconazole reduced keratinolytic acid proteinase activity in the culture-supernate to 40-70% of the control value, while bifonazole showed 50% reduction of the activity at a concentration of 10 micrograms/ml. These results indicate that lanoconazole is mainly distributed and retained in the stratum corneum after topical application where it exerts strong antifungal activity.

Administration, Topical↗

Retinal toxicity of nitric oxide released by administration of a nitric oxide donor in the albino rabbit.

PURPOSE: Nitric oxide (NO), which has been identified as an endothelium-derived relaxing factor, might be involved in regulation of retinal circulation and intraocular pressure. Recently, it was suggested that NO might also be related to neuronal excitotoxicity mediated by the N-methyl-D-aspartate receptor and to the pathologic changes induced by some kinds of uveitis. However, ocular toxicity of NO released by an NO donor has not been clearly demonstrated. In the current study, NO neurotoxicity in the retina was investigated. METHODS: S-nitroso-N-acetyl-DL-penicillamine (SNAP, 200 nmol) was injected into the vitreous of albino rabbits as an NO donor. The changes of retinal function were evaluated at 1, 2, and 3 hours and 1 and 4 weeks after SNAP injection, using electroretinogram and visual-evoked potentials. Histologic changes of the retina were also examined. RESULTS: Injection of SNAP reduced the a-wave amplitude. In contrast, the amplitudes of the oscillatory potentials were increased during the 3-hour observation period. Histologic examination showed vacuolar degeneration and loss of the nuclei of the photoreceptors. In the inner retina, some ganglion cells were lost, and cell density in the internal nuclear layer was decreased. CONCLUSION: Retinal toxicity of NO was demonstrated functionally and histologically, suggesting that NO may play a pathophysiologic role in retinal ischemia or in degenerative retinal diseases.

Animals↗