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Biomedical subjects

M Yoshii

Publications and source records attributed to M Yoshii.

At least 19 recordsLinked to original sources

Optic nerve hyperintensity on T2-weighted images among patients with pituitary macroadenoma: correlation with visual impairment.

PURPOSE: Visual acuity (VA) disturbance other than field defect is important in evaluating patients with pituitary macroadenoma. The purpose of this study was to evaluate MR imaging appearances of optic nerves in patients with pituitary macroadenoma and to ascertain whether visual impairment was correlated with abnormality in optic nerve signal intensity. PATIENTS AND METHODS: Twenty-seven patients with pituitary macroadenoma were examined. Optic nerves were evaluated on T2-weighted images and correlations of signal intensity abnormality with VA disturbance, visual field disturbance, degree of optic chiasm compression, pathologic findings of surgical specimen, and disease duration were statistically analyzed. Correlations between recovery of VA after treatment and the above-mentioned factors were also determined. RESULTS: Coronal T2-weighted images demonstrated unilateral optic nerve hyperintensity lesions in 9 patients. Bilateral signal intensity abnormality of the optic nerve was seen in 5 patients. Signal intensity abnormality of the optic nerve was seen at the site of compression and in the ventral side of the tumor. These patients did not demonstrate signal intensity abnormality posterior to the tumor. Presence of such signal intensity abnormalities was correlated with the degree of optic chiasmal compression and with VA disturbance. Recovery of VA after treatment was correlated with disease duration. CONCLUSION: Hyperintensity of the optic nerves ventral to the pituitary macroadenoma was associated with VA impairment. Recovery of VA after treatment was correlated with disease duration. MR imaging of the optic nerves can provide valuable information for management of pituitary macroadenoma.

Adenoma↗

Genetic variation and geographic distribution of porcine reproductive and respiratory syndrome virus in Japan.

Porcine reproductive and respiratory syndrome virus (PRRSV) has two genotypes, the North American-type (NA-type) and the European-type (EU-type), and each genotype is also genetically diverged. We sequenced the ORF5 gene of 30 PRRSVs isolated from 23 prefectures of Japan during 1992 and 1993 and during 2000 and 2001. All of the isolates were of the NA-type. Phylogenetic analysis of the overall NA-type viruses isolated from around the world identified five major genetic clusters. The 1992-1993 Japanese samples belonged to only two genetic clusters, while the 2000-2001 samples included more diverged ORF5 genomes. One genetic cluster, which included 63% (20/32) of Japanese isolates, one Taiwanese isolate and one Chinese isolate, was mainly found in the eastern part of Japan. Another genetic cluster, which was found in various areas around the world, was distributed in the western part of Japan.

Animals↗

Diagnostic value of carotid intima-media thickness and plaque score for predicting target organ damage in patients with essential hypertension.

Carotid intima-media thickness (IMT) assessed by ultrasonography is regarded as an early predictor of general arteriosclerosis in patients with essential hypertension. However, the methods of measuring IMT have not been globally standardized, and it remains unclear whether conventional measurement of IMT represents the prevalence of hypertensive target organ damage. In this study, we verified the association between several commonly used carotid ultrasonographical parameters and the severity of hypertensive target organ damage (retinal arteriosclerosis, microalbuminuria, left ventricular hypertrophy (LVH)). Carotid ultrasonography, echocardiography, urinalysis, and funduscopy were performed in 184 patients (64 +/- 12 years, 96 males and 88 females) with various stages of essential hypertension. Carotid arteriosclerosis was assessed using four methodologically different methods: conventional-IMT, maximum-IMT (Max-IMT), Mean-IMT, and Plaque Score (the sum of all plaque thicknesses). Age and all carotid ultrasonographical parameters were significantly associated with albuminuria, retinal arteriosclerosis, and left ventricular mass index. High-sensitivity CRP was significantly correlated with retinopathy and LVH. Carotid parameters in patients with histories of cardiovascular events were significantly greater in those without events. Among all carotid parameters, Max-IMT showed the highest correlation coefficient of the severity of target organ damage, and showed significant association with CRP. Stepwise regression analysis revealed that Max-IMT was the independent factor for predicting target organ damage. Max-IMT is suggested to be the most reliable and simplest parameter for predicting hypertensive target organ damage including microangiopathy in patients with essential hypertension.

Albuminuria↗

Nonsuppurative encephalitis in piglets after experimental inoculation of Japanese encephalitis flavivirus isolated from pigs.

Nonsuppurative encephalitis was experimentally induced in 3-week-old piglets by a single intravenous inoculation of either of two strains (IB 2001 or AS-6) of Japanese encephalitis flavivirus (JEV) isolated from field pigs. The lesions, which consisted of neuronal necrosis, neuronophagia, glial nodules, and perivas-cular cuffing, were distributed in the cerebrum, midbrain, pons, medulla oblongata, and cerebellum, particularly in the gray matter of the frontal and temporal lobes and thalamus. The gray matter of the spinal cord of piglets that were given the AS-6 strain also was affected. JEV antigen was immunohistochemically detected in the cytoplasm of the nerve cells in the cortex of the frontal and temporal lobes and in the gray matter of the thalamus and midbrain. Two JEV strains isolated from field pigs exhibited neurovirulence, inducing nonsup-purative encephalitis in piglets.

Animals↗

Positive association of CYP11B2 gene polymorphism with genetic predisposition to essential hypertension.

Predispositions to essential hypertension and cardiovascular diseases are possibly associated with gene polymorphisms of the renin-angiotensin system. Gene polymorphisms of angiotensinogen and angiotensin-converting enzyme genes have been suggested to be risk factors for hypertension and myocardial infarction. Concerning the polymorphism of aldosterone synthase (CYP11B2) gene, earlier studies have shown inconsistent results in terms of its relation to hypertension. In the present case-control study, we investigated the association of -344T/C polymorphism in the promoter region of human CYP11B2 gene with genetic predisposition to hypertension. The genotype of -344T/C polymorphism was determined in essential hypertension subjects (n=250) and normotensive subjects (n=221). The distributions of three genotypes (TT, TC, and CC) were significantly different between the hypertensive and the normotensive groups (chi(2)=9.61, P=0.008). Namely, the frequency of C allele was higher in the hypertensive patients than in the normotensive subjects (34.2 vs 26.5%, P=0.010). Our data suggest that the -344C allele of CYP11B2 gene polymorphism is associated with the genetic predisposition to develop essential hypertension.

Adult↗

[The significance of early detection for prostate cancer in mass screening].

PURPOSE: In Mitaka city, mass screening for prostate cancer was conducted for 3 years from 1995 to 1997. Clinical stages were compared between patients found by screening and those diagnosed at our clinic during the same time. The significance of serum-free prostate specific antigen (PSA) in mass screening for prostate cancer was examined. MATERIAL AND METHODS: A prospective clinical trial was conducted on men aged 50 years or older. The primary examination consisted of taking the international prostate symptom score, quality of life score, PSA (Tandem-R) and digital rectal examination (DRE). If PSA was greater than 4.0 ng./ml and/or if DRE suggested cancer, transrectal ultrasound-guided sextant prostate biopsies were indicated. RESULTS: Of the men screened, 23.2% (320/1375) had serum PSA greater than 4.0 ng./ml. and/or suspicious findings on DRE. Biopsy was performed in 199 of 320 (62.1%). Cancer was detected in 21 (1.5%, 21/1375). Prostate cancer was found in one case among 154 males (0.65%, 1/154) who were screened twice or more. The cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic (Wilcoxon's rank-sum test: p = 0.0047). Receiver operating characteristics analysis showed that the optimal free PSA-to-PSA ratio was 12%. Positive predictive value increased from 18% to 50% when free PSA-to-PSA ratio was combined with PSA. CONCLUSION: 1. Cancer detection rate was 1.5% in the mass screening in Mitaka City. 2. Cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic. 3. Free PSA determination might eliminate unnecessary biopsies in men with PSA above 4.0 ng./ml with minimal loss of cancer detection.

Aged↗

[Comparisons of factors affecting voiding disorders between patients with benign prostate hyperplasia and volunteers].

PURPOSE: The prostate size and motivation to visit clinics were investigated in patients with prostate hyperplasia. OBJECTS AND METHODS: One hundred ninety-five patients who had urinary symptoms and visited our outpatient clinic between September 1994 and October 1999 and 268 age-matched volunteers in Mitaka City who underwent a medical examination of the prostate in June 1997 were compared. International Prostate Symptom Score (IPSS), Quality Of Life Score (QOL score), residual urine volume, prostate volume and urinary flow rate were measured. RESULTS: The prostate volume of the volunteers was 20-25 cm3 irrespective of the age. The prostate size of the outpatients was larger than that of the volunteers for every age group. IPSS and QOL score were significantly higher in the outpatients than in the volunteers. Diurnal urinary frequency and sense of residual urine contributed to the discrimination index of the two groups more significantly than the other scores. There was a significant correlation between prostate volume and residual urine volume. The score of weak urinary steam was inversely and significantly correlated with peak urinary flow rate. CONCLUSIONS: There was no age-related enlargement of the prostate gland. The prostate gland was significantly larger in the patients than in the volunteers even in those in their fifties. Urinary frequency and sense of residual urine are important factors for men to seek and receive medical care.

Adult↗

[A case of fundus albipunctatus with a retinol dehydrogenase 5 gene mutation in a child].

BACKGROUND: We examined a family with fundus albipunctatus in which mutation of the retinol dehydrogenase 5(RDH 5) gene was suspected to be the cause of this disease. CASE: An 8-year-old girl had diffuse multiple white dots in her fundus except for the macula. She had good central vision. The amplitude of her electroretinogram wave was low, but it recovered after three hours of dark adaptation. Dark adaptometry showed an elevated threshold for rod adaptation. No visual field loss was observed. A homozygous missense mutation was found in exon 5 of the RDH 5 gene that substituted histidine for arginine at codon 280(Arg 280 His). Her mother had a normal fundus but was heterozygous for the same mutation. CONCLUSION: A missense mutation of RDH 5(Arg 280 His) was found in a Japanese family with fundus albipunctatus.

Alcohol Oxidoreductases↗

The anti-dementia drug nefiracetam facilitates hippocampal synaptic transmission by functionally targeting presynaptic nicotinic ACh receptors.

Nefiracetam, a pyrrolidone derivative developed as an anti-dementia drug, persistently potentiated currents through neuronal nicotinic acetylcholine (ACh) receptors (alpha7, alpha4beta2) expressed in Xenopus oocytes, and the potentiation was blocked by either the selective protein kinase C (PKC) inhibitors, GF109203X and staurosporine, or co-expressed active PKC inhibitor peptide. In primary cultures of rat hippocampal neurons, nefiracetam increased the rate of nicotine-sensitive miniature excitatory postsynaptic currents, without affecting the amplitude, and the increase was inhibited by GF109203X. In addition, the drug caused a marked increase in the glutamate release from electrically stimulated guinea pig hippocampal slices, and the effect was abolished by the nicotinic ACh receptor antagonists, alpha-bungarotoxin and mecamylamine. Nefiracetam induced a long-lasting facilitation of synaptic transmission in both the CA1 area and the dentate gyrus of rat hippocampal slices, and the facilitation was inhibited by alpha-bungarotoxin and mecamylamine. Such facilitatory action was still found in the hippocampus with selective cholinergic denervation. The results of the present study, thus, suggest that nefiracetam enhances activity of nicotinic ACh receptors by interacting with a PKC pathway, thereby increasing glutamate release from presynaptic terminals, and then leading to a sustained facilitation of hippocampal neurotransmission. This may represent a cellular mechanism underlying the cognition-enhancing action of nefiracetam. The results also provide the possibility that nefiracetam could be developed as a promising therapeutic drug for senile dementia or Alzheimer's disease.

Animals↗

Molecular characterization and physiological role of ascorbate peroxidase from halotolerant Chlamydomonas sp. W80 strain.

A cDNA clone encoding an ascorbate peroxidase was isolated from the cDNA library from halotolerant Chlamydomonas W80 by a simple screening method based on the bacterial expression system. The cDNA clone contained an open reading frame encoding a mature protein of 282 amino acids with a calculated molecular mass of 30,031 Da, preceded by the chloroplast transit peptide consisting of 37 amino acids. In fact, ascorbate peroxidase was localized in the chloroplasts of Chlamydomonas W80 cells; the activity was detected in the stromal fraction but not in the thylakoid membrane. The deduced amino acid sequence of the cDNA showed 54 and 49% homology to chloroplastic and cytosolic ascorbate peroxidase isoenzymes of spinach leaves, respectively. The enzyme from Chlamydomonas W80 cells was purified to electrophoretic homogeneity. The molecular properties of the purified enzyme were similar to those of the other algal ascorbate peroxidases rather than those of ascorbate peroxidases from higher plants. The enzyme was relatively stable in ascorbate-depleted medium compared with the chloroplastic ascorbate peroxidase isoenzymes of higher plants. The presence of NaCl (3%) as well as of beta-d-thiogalactopyranoside was needed for the expression of Chlamydomonas W80 ascorbate peroxidase in Escherichia coli.

Amino Acid Sequence↗

Anticonvulsant actions of nefiracetam on epileptic EL mice and their relation to peripheral-type benzodiazepine receptors.

Anticonvulsant actions of the nootropic drug nefiracetam were studied using EL mice, an animal model of epilepsy, in which peripheral-type benzodiazepine receptors (PBRs) might be involved in their epileptogenesis. Nefiracetam, when administered orally t o EL mice, inhibited convulsions induced by the PBR agonist, Ro 5-4864, with an ED(50) of 17.2 mg/kg, whereas it did not inhibit the drug-induced convulsions in control DDY mice. When administered intravenously (i.v.) to DDY mice, nefiracetam and other piracetam-like nootropics inhibited the Ro 5-4864-induced convulsions in the sequence of nefiracetam>aniracetam>>oxiracetam, piracetam. Spontaneous EL mouse seizures were also inhibited by these nootropics with a similar rank order of potencies. Binding studies for PBRs, performed on crude membranes of brain tissues of these mice, revealed that [3H]Ro 5-4864 and [3H]PK 11195 bindings were both inhibited by micromolar concentrations of nootropic agents in the sequence of nefiracetam> aniracetam>>oxiracetam, piracetam. The results suggest that nefiracetam may exert an anticonvulsant action through interacting with a low-affinity type of PBR in the brain, and could be developed as a promising therapeutic drug for neurological disorders including epilepsies.

Animals↗

Bile acid sulfonate and 7-alkylated bile acid analogs: effect on intestinal absorption of taurocholate and cholesterol 7alpha-hydroxylase activity in cultured rat hepatocytes.

The effects of sulfonate analogs of cholic (C), chenodeoxycholic (CDC), and ursodeoxycholic acid (UDC) and three 7-alkylated CDCs--7-methyl-, 7-ethyl-, and 7-propyl-CDCs--on taurocholate absorption from rat terminal ileum in situ and on cholesterol 7alpha-hydroxylase activity in primary culture of the rat liver were investigated. The sulfonate analogs of two dihydroxy bile acids CDC and UDC, but not C, significantly decreased the absorption of taurocholate. Taurine conjugates of 7-alkylated CDC slightly decreased the taurocholate absorption, and tauro-7-propyl-CDC significantly suppressed the absorption. Although the sulfonate analogs of C and CDC reduced cholesterol 7alpha-hydroxylase activity by 40% and 60% compared to control, UDC-sulfonate analog did not affect enzymatic activity. These results were consistent with those of the lead compounds, C, CDC, and UDC. The introduction of methyl group at C-7 position of CDC attenuated the reduction in cholesterol 7alpha-hydroxylase activity by CDC. However, elongation of the alkyl group resulted in an inhibitory effect. The present study revealed the following: 1) bile acid sulfonates act on cholesterol and bile acid metabolism in a similar manner as taurine conjugated bile acids; and 2) the biologic properties of CDC could be altered by the introduction of alkyl group at C-7 position.

Animals↗

Enhancing effect of 5 alpha-cyprinol sulfate on mucosal membrane permeability to sodium ampicillin in rats.

Effect of 5 alpha-cyprinol sulfate, a bile alcohol sulfate specific to carp bile, on rectal membrane permeability to sodium ampicillin (AMP Na) was examined in rats. AMP Na is not easily absorbed through rat rectal membrane without aid. 5 alpha-Cyprinol sulfate significantly enhanced the rectal membrane permeability to AMP Na even at a low concentration (6.25 mM), though sodium taurocholate needed a higher concentration (25 mM). Co-administration of phosphatidylcholine significantly suppressed the enhancing action of both sodium taurocholate and 5 alpha-cyprinol sulfate. On the other hand, calcium ion did not suppress the action of 5 alpha-cyprinol sulfate, although it did clearly suppress the action of sodium taurocholate. In conclusion, 5 alpha-cyprinol sulfate was found to have a potent enhancing effect on mucosal membrane permeability to water-soluble compounds. The enhancing mechanism of 5 alpha-cyprinol sulfate appeared to be different from that of sodium taurocholate.

Ampicillin↗

A solid-state culture system using a cellulose carrier containing defined medium as a useful tool for investigating characteristics of koji culture.

The purpose of this article is to establish a new solid-state culture system that uses a defined medium and allows control of the chemical factors in the medium in solid-state cultivation. To achieve this purpose, we produced a solid substrate, in which the defined medium was packed in a cellulose carrier with agar, and named it "cellulose agar cube (CA-cube)". In order to obtain growth conditions similar to koji culture, we then determined the moisture content of the CA-cube. Five runs of column reactor operations were carried out at various moisture contents of the CA-cube in the range of 50-90%. A very similar mycelial morphology to that of koji culture was observed on the surface of CA-cube with moisture content lower than 63%. The glucoamylase production and the production ratio of glucoamylase to alpha-amylase (G/A ratio) were both increased exponentially with decreasing moisture content and reached 237.5 units per g dry solid and 13.59, respectively, at the moisture content of 50%, which are almost comparable to those of koji culture. In addition, the glucoamylase "glaB", which is mainly produced in koji culture, was observed in the CA-cube culture with low moisture content. These results indicate that growth conditions similar to koji culture could be attained by the column reactor culture with the CA-cube.

Journal Article↗

The significance of the free-to-complexed prostate-specific antigen (PSA) ratio in prostate cancer detection in patients with a PSA level of 4.1-10.0 ng/mL.

OBJECTIVE: To compare the ratio of free prostate specific antigen (fPSA), total PSA (tPSA) and complexed PSA (cPSA, measured using a novel immunoassay) with other variables used to detect prostate cancer in patients with intermediate serum PSA levels of 4.1-10.0 ng/mL. PATIENTS AND METHODS: From July 1997 to August 1998, 140 consecutive patients were assessed; all had intermediate serum PSA levels and/or abnormal findings on a digital rectal examination. All patients underwent transrectal ultrasonography (TRUS)-guided biopsy, and the prostate and transition zone volumes were determined by TRUS. Free and tPSA were measured using the Tandem-R assay (Hybritech Corp., San Diego, CA). PSA complexed with alpha1-antichymotrypsin (cPSA) was measured using an appropriate assay. The ability of cPSA, free-to-total PSA ratio (f/tPSA), free-to-complexed PSA ratio (f/cPSA), tPSA density of the whole prostate (PSAD), of the transition zone (tPSATZ), and cPSA density of the whole prostate (cPSAD) and of the transition zone (cPSATZ) to improve the power of PSA in detecting prostate cancer was evaluated using receiver operating characteristic (ROC) curves. Results Of the 140 patients, 126 had histologically confirmed benign disease and 14 had prostate cancer. The cPSA alone had better specificity for detecting prostate cancer than had tPSA alone but the difference was not significant. The area under the ROC curve for f/cPSA was larger than those for all other variables. With a 93% sensitivity for detecting prostate cancer, a f/cPSA threshold of 25% would result in fewer unnecessary biopsies (40% f/cPSA specificity) than with all other PSA variables. The difference in the resolution was significant between f/cPSA and tPSA, cPSA, tPSAD and tPSATZ, but not with f/tPSA, cPSAD or cPSATZ. In patients with a prostate volume of < 30 mL, the cPSATZ showed better specificity for prostate cancer than tPSA alone. CONCLUSION: Measuring the level of cPSA and its derivatives may provide better differentiation of prostate cancer and benign disease than tPSA alone in patients with a tPSA level of 4.1-10.0 ng/mL.

Aged↗

Presynaptic nicotinic acetylcholine receptors as a functional target of nefiracetam in inducing a long-lasting facilitation of hippocampal neurotransmission.

Nefiracetam (1-10 microM), a nootropic (or cognition-enhancing) agent, persistently potentiated currents through Torpedo acetylcholine (ACh) receptors expressed in Xenopus oocytes as a result of interacting with a protein kinase C pathway and the ensuing protein kinase C phosphorylation of the receptors. A similar effect was found in neuronal nicotinic ACh receptors (alpha4beta2 and alpha7). In contrast, the other nootropic agents such as piracetam and aniracetam had no potentiating action on the receptors. A sustained enhancement in the activity of nicotinic ACh receptors induced by nefiracetam caused a marked increase in the glutamate release, leading to a long-term potentiation-like facilitation of hippocampal synaptic transmissions. One of the consistent neuropathologic features of the Alzheimer brain is a loss of nicotinic ACh receptors. This fact, together with the results of our study, raises the possibility that the loss of nicotinic ACh receptors may be a key factor in the decline of cognitive function observed in Alzheimer disease and that agents targeting neuronal nicotinic ACh receptors like nefiracetam could, therefore, be of great therapeutic importance.

Acetylcholine↗

Cellular mechanism of action of cognitive enhancers: effects of nefiracetam on neuronal Ca2+ channels.

Cellular mechanisms underlying the cognition-enhancing actions of piracetam-like nootropics were studied by recording Ca2+ channel currents from neuroblastoma x glioma hybrid (NG108-15) cells and Xenopus oocytes expressing Ca2+ channels. In NG108-15 cells, nefiracetam (1 microM) produced a twofold increase in L-type Ca2+ channel currents. A similar, but slightly less potent effect was observed with aniracetam, whereas piracetam and oxiracetam exerted no such effects. Cyclic AMP analogs mimicked the nefiracetam action. N-type Ca2+ channel currents inhibited by leucine (Leu)-enkephalin by means of inhibitory G proteins (Go/Gi) were recovered promptly by nefiracetam, whereas those inhibited by prostaglandin E1 via stimulatory G proteins were not affected by nefiracetam. Cells treated with pertussis toxin (500 ng/mL, > 20 hours) were insensitive to nefiracetam. In Xenopus oocytes functionally expressing N-type (alpha1B) Ca2+ channels and delta-opioid receptors, nefiracetam was also effective in facilitating the recovery from Leu-enkephalin-induced inhibition. These results suggest that nefiracetam, and possibly aniracetam, may activate N- and L-type Ca2+ channels in a differential way depending on how they recover from Go/Gi-mediated inhibition.

Animals↗