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Biomedical subjects

M Uchiyama

Publications and source records attributed to M Uchiyama.

At least 127 records · Page 7Linked to original sources

An event-related potential study in schizophrenia using Japanese sentences.

To examine the neurophysiological and cognitive characteristics of language disorder in schizophrenia, the N400 component and late positive component (LPC) of event-related potentials (ERPs) were investigated in medicated schizophrenic patients and health comparison subjects. The subjects were required to indicate whether Japanese sentence completions were semantically congruous or incongruous. The ERPs for the range of 300-500 ms to the incongruous completions contained a more negative component (N400), followed by LPC, which was inversely more positive for the incongruous than congruous condition. The N400 effect and the mean amplitude of the LPC were reduced in the patients. The attenuated N400 effect in schizophrenics mainly originated from an enhanced negativity for the congruous completions, suggesting that the use of context is poor in schizophrenia.

Adult↗

Activity of midbrain reticular formation and neocortex during the progression of human non-rapid eye movement sleep.

To clarify the neural correlates and brain activity during the progression of human non-rapid eye movement (NREM) sleep, we examined the absolute regional cerebral blood flow (rCBF) during light and deep NREM sleep and during wakefulness in normal humans using positron emission tomography with H(2)(15)O. Relative changes in rCBF during light and deep NREM sleep in comparison to the rCBF during wakefulness were also analyzed. During light NREM sleep, the rCBF in the midbrain, in contrast to that in the pons and thalamic nuclei, did not decrease when compared to that during wakefulness, whereas rCBF decreased in the left medial frontal gyrus, left inferior frontal gyrus, and left inferior parietal gyrus of the neocortex. During deep NREM sleep, the rCBF in the midbrain tegmentum decreased, and there was a marked and bilateral decrease in the rCBF in all neocortical regions except for the perirolandic areas and the occipital lobe. There have been three groups of brain structures, each representing one type of deactivation during the progression of NREM sleep. The activity of the midbrain reticular formation is maintained during light NREM sleep and therefore represents a key distinguishing characteristic between light and deep NREM sleep. Selective deactivation of heteromodal association cortices, including those related to language, occurs with increasingly deep NREM sleep, which supports the recent theory that sleep is not a global, but it is a local process of the brain.

Adult↗

Alleic variants of human melatonin 1a receptor: function and prevalence in subjects with circadian rhythm sleep disorders.

The human melatonin 1a (hMella) receptor gene was screened for mutations using genomic DNA samples from patients with circadian rhythm sleep disorders and control subjects by single strand conformational polymorphism analysis (SSCP). We found seven mutations, two of which predict amino acid changes R54W and A157V, respectively. The prevalence of the R54W variant and that of the A157V variant were several times more common in non-24-h sleep-wake syndrome subjects than among control subjects, although the incidence was not significant in our study group. When expressed in COS-7 cells, the R54W mutant receptor exhibited significantly reduced B(max) and slightly enhanced affinity (reduced K(d)) compared to the wild type receptor, while the A157V variant receptor showed similar binding characteristics to the wild type. The identification of variants in the hMella receptor will provide a useful tool for analyzing genetic predisposition toward various diseases related to melatonin function and to clarify the physiological role of melatonin receptors in humans.

Alleles↗

Chemical and immunochemical characterization of limulus factor G-activating substance of Candida spp.

The limulus test is a well-established method for the diagnosis of both gram (-) sepsis and invasive fungal infection. To diagnose deep-seated fungal infections, a (1-->3)-beta-D-glucan-specific chromogenic kit (Fungitec G test MK) has been developed and applied clinically. It is suggested that the limulus reactive substance was released from the fungi to the blood, however, its chemical properties were not precisely examined in detail because of the limited quantity available. In this study, we used chemically defined liquid medium to culture Candida spp. and collected the water soluble fraction, CAWS. The yield of CAWS was circa 100 mg/l, independent of the strain of Candida. CAWS reacted with limulus factor G (Fungitec G test MK) at concentrations as low as 100 ng/ml. Limulus factor G reactivity of CAWS was sensitive to (1-->3)-beta-glucanase, zymolyase and was, at least in part, bound to ConA-agarose. The ConA-bound fraction also reacted with anti-beta-glucan antibody. CAWS is mainly composed of mannan and (1-->6)-beta-glucan, in addition to protein, assessed by 1H-NMR spectroscopy. CAWS also reacted with typing sera of Candida spp., specific for cell wall mannan. Chemical, immunochemical and biochemical analyses of CAWS strongly suggested that the limulus factor G-activating substance was a mannan-beta-glucan complex, present within the architecture of the yeast cell wall.

Candida↗

Solubilization of yeast cell-wall beta-(1-->3)-D-glucan by sodium hypochlorite oxidation and dimethyl sulfoxide extraction.

The limulus test is a well-established method for the diagnosis of both Gram-negative sepsis and invasive fungal infection. To diagnose fungal infections, a beta-(1-->3)-D-glucan-specific chromogenic kit (Fungitec G test MK) has been developed and applied clinically. We are concentrating our main efforts on developing a better standard to improve the precision of this method. To this end, we have successfully developed a protocol to obtain a soluble Candida spp. beta-(1-->3)-D-glucan (CSBG) by sodium hypochlorite (NaClO) oxidation and subsequent dimethyl sulfoxide (Me2SO) extraction (yield of 9.6 +/- 4.1%) of acetone-dried whole-cell preparations. The beta-glucan fraction is free from the cell-wall mannan, gives a symmetrical peak by gel filtration, and is soluble in dilute NaOH. The product is composed mainly of beta-(1-->3)- and beta-(1-->6)-D-glucosidic linkages. The specific activity of the beta-glucan is comparable with pachyman when combined with the Fungitec G test as the standard glucan and reacted as low as 10(-11) g/mL.

Candida↗

Preoperative cervical cytology in endometrial carcinoma and its clinicopathologic relevance.

OBJECTIVE: The aim of this study was to assess the significance of malignant or suspicious cervical cytology in preoperative identification of poor prognostic factors in endometrial carcinoma and to determine whether preoperative abnormal cervical cytology is an independent prognostic factor for endometrial carcinoma. METHODS: We evaluated the correlation between preoperative cervical cytology and postoperative clinicopathologic findings, sites of metastasis, and receptor status from 99 surgically staged patients with endometrial carcinoma. RESULTS: Sixty-eight patients (68.7%) had normal cervical cytology, 1 (1.0%) had atypical cytology suspicious for malignancy, and 30 (30.3%) had malignant cytology on preoperative cervical cytology. Malignant and suspicious cervical smears were statistically correlated with surgical stage (P = 0.001), histopathology (P = 0.010), tumor grade (P = 0.012), depth of myometrial tumor invasion (P = 0.001), cervical involvement (P = 0. 01), lymph node metastases (P = 0.002), adnexal metastases (P = 0. 012), progesterone receptor (P = 0.007), and estrogen receptor (P = 0.031). No association was found between preoperative cervical cytology and patients' age or peritoneal cytology. Univariate analysis showed that cervical cytology was related to survival (P = 0.018). However, multivariate analysis of cervical cytology, stage, grade, and myometrial invasion showed that preoperative cervical cytology was not a significant prognosticator for survival. CONCLUSION: Patients with endometrial carcinoma who have malignant or suspicious cytology detected by preoperative cervical cytology are at increased risk of having known poor prognostic factors. However, positive preoperative cervical cytology itself does not appear to be an independent prognostic factor and probably should not influence treatment decisions in endometrial cancer.

Adult↗

Prognostic significance of progesterone receptor immunohistochemistry for lymph node metastases in endometrial carcinoma.

OBJECTIVE: The aim of this study was to determine whether progesterone receptor (PR), estrogen receptor (ER), p53 protein, and proliferating cell nuclear antigen (PCNA) expression constitute independent prognostic factors for lymph node metastases in endometrial carcinoma using immunohistochemical techniques on hysterectomy and biopsy specimens. METHODS: We evaluated the correlation between lymph node metastases and PR/ER immunohistochemistry, p53/PCNA expression, age, tumor grade, myometrial tumor invasion, cervical involvement, and ovarian metastases in a series of 99 cases of primary endometrial carcinoma surgically staged with systemic pelvic lymphadenectomy and para-aortic lymph node biopsy. RESULTS: Lymph node metastases from endometrial carcinoma were statistically correlated with negative PR immunohistochemistry (P = 0.001), intense p53 expression (66% or more of the tumor cells stained, P = 0.003), deep myometrial tumor invasion (greater than one-half, P = 0.001), and cervical involvement (P = 0.001). Tumor grade showed borderline statistical significance for lymph node metastases (P = 0.058). On multivariate analysis, negative PR, intense p53 expression, and cervical involvement were significant prognostic variables for lymph node metastases (P = 0.0001, 0.0023, and 0.002, respectively). Immunohistochemical study indicated that the PR status on preoperative biopsy specimens and hysterectomy specimens was in good agreement, but p53 status was not. Age, ovarian metastases, ER immunohistochemistry, and PCNA expression were not significantly related to lymph node metastases. CONCLUSION: PR immunohistochemistry appeared to be the most powerful prognostic factor associated with lymph node metastases in endometrial carcinoma, independent of other clinicopathological parameters.

Adult↗

Identification of 1-aminocyclopropane-1-carboxylic acid synthase genes controlling the ethylene level of ripening fruit in Japanese pear (Pyrus pyrifolia Nakai).

The shelf life of Japanese pear fruit is determined by its level of ethylene production. Relatively high levels of ethylene reduce storage potential and fruit quality. We have identified RFLP markers tightly linked to the locus that determines the rate of ethylene evolution in ripening fruit of the Japanese pear. The study was carried out using sequences of two types of 1-aminocyclopropane-1-carboxylic acid (ACC) synthase genes (PPACS1 and pPPACS2) and a ACC oxidase gene (PPAOX1) as probes on 35 Japanese pear cultivars expressing different levels of ethylene (0.0 to approximately 300 microl/kg fresh weight/h) in ripening fruit. When total DNA was digested with HindIII and probed with pPPACS1, we identified a band of 2.8 kb which was specific to cultivars having very high ethylene levels (> or = 10 microl/kg f.w./h) during fruit ripening. The probe pPPACS2 identified a band of 0.8 kb specific to cultivars with moderate ethylene levels (0.5 microl/kg f.w./h-10 microl/kg f.w./h) during fruit ripening. The cultivars that produce high levels of ethylene possess at least one additional copy of pPPACS1 and those producing moderate levels of ethylene have at least one additional copy of pPPACS2. These results suggest that RFLP analysis with different ACC synthase genes could be useful for predicting the maximum ethylene level during fruit ripening in Japanese pear.

Amino Acid Oxidoreductases↗

Hypercholesterolemia and glomerular diseases in urinary screening of school children.

Although hypercholesterolemia frequently accompanies nephrotic syndrome, high serum total cholesterol (TC) levels are occasionally seen in children with non-nephrotic glomerular diseases. However, little is known of the significance, if any, of these elevated serum TC levels in non-nephrotic glomerular diseases. During the past 5 years, a total of 256,179 school children received yearly urinary screening at school for renal diseases and 1,702 children (0.66% of the total, although 174 children dropped out) had proteinuria and/or hematuria. Using the data obtained from the 1,528 children, we studied whether there is any association between serum TC levels and the presence of glomerular diseases. The detection rate of glomerular diseases (IgA nephropathy, membranoproliferative glomerulonephritis, focal segmental glomerular sclerosis, etc.) in the subjects with high serum TC levels (> or =200 mg/dl) was significantly higher (16 of 161, 9.94%, P<0.001) than in those with normal serum TC levels (<200 mg/dl) (10 of 1,367, 0.73%). There were no significant differences in serum albumin and blood urea nitrogen levels between the two groups. We conclude that children with chance proteinuria and/or hematuria may be at higher risk for glomerulonephritis of various types when they have unexplained hypercholesterolemia, and that measurement of serum cholesterol levels may be useful in urinary screening for renal diseases.

Adolescent↗

Apolipoprotein E epsilon 4 allele and nephrotic glomerular diseases in children.

Hyperlipidemia is a well-recognized complication of the nephrotic syndrome and is a factor contributing to the progression of the initial glomerular injury and the development of glomerulosclerosis. Apolipoprotein E (apoE) is a plasma protein and apoE epsilon 4 allele is associated with higher plasma cholesterol levels. With this in mind, we studied apoE phenotypes and alleles in children with nephrotic glomerular diseases (NGD, n=29), including idiopathic nephrotic syndrome (n=16), membranoproliferative glomerulonephritis (n=7), and focal segmental glomerulosclerosis (FSGS, n=6). Children with NGD had a higher epsilon 4 allele frequency (20.7%) than controls (10.8%), and those with FSGS had both higher apoE4/3 (66.7%) and epsilon 4 allele (33.3%) frequencies than controls (20.4% and 10.8%, respectively). In IgA nephropathy (n=30, disease controls), no significant association with specific apoE was found. Further studies are needed to clarify the significance of the observed high frequencies of apoE epsilon 4 allele in children with NGD and apoE4/3 phenotype distribution in FSGS.

Adolescent↗

Changes in serum apolipoprotein concentrations after L-thyroxine therapy in infants with congenital hypothyroidism.

To further characterize the impact of thyroid hormones on the serum lipid profile, we studied serum apolipoproteins in infants with congenital hypothyroidism before and after L-thyroxine (L-T4) replacement therapy. Serum high-density lipoprotein cholesterol (HDLC) decreased after L-T4 therapy. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels did not change significantly after therapy. Two months after L-T4 replacement therapy, serum apolipoprotein A-I (apo A-I), C-III, and E declined and apo B increased significantly. No significant changes were observed for serum concentrations of apo A-II and C-II after L-T4 substitution. We conclude that in infants, thyroid hormone reduces serum levels of apo A-I, the principal protein component of HDLC, and this may contribute to the decline of serum HDLC concentrations after L-T4 replacement therapy.

Apolipoproteins↗

Inflammatory and immunopharmacological activities of meta-periodate oxidized zymosan.

Zymosan (ZYM), a strong complement-activating yeast cell preparation composed mainly of mannan and beta-glucan moieties, is a potent inflammatory substance with immunopharmacological activity. We previously analyzed the metabolism of ZYM in mice and found that it was deposited in liver and spleen for at least several months and then gradually oxidatively degraded. In this paper, we prepared oxidized ZYM by sodium metaperiodate oxidation (NaIO4) and borohydride reduction (I/B-ZYM) and/or limited hydrolysis of oxidized moieties (I/B/H-ZYM). Activities of the resulting products were assessed by (i) vascular permeability in mice, (ii) H2O2 synthesis by macrophages, (iii) TNF-alpha synthesis by macrophages, and (iv) reactivity to anti-ZYM sera. As a general trend, NaIO4, oxidation products exhibited reduced, but still significant, activity. Interestingly, the H2O2 production induced by I/B/H-ZYM was significantly reduced after extensive sonication. Antagonist(s) for H2O2 synthesis were concomitantly solubilized by sonication of I/B/H-ZYM. On the contrary, TNF-alpha production induced by I/B/H-ZYM was comparable with that of ZYM. These facts strongly suggest that highly branched 1,3-beta- and 1,6-beta-glucosidic linkages resistant to NaIO4 oxidation are important for biological activity of ZYM. Further, the minimal structure in ZYM necessary for biological activity may depend on the activity tested.

Animals↗

Insertion of the cuffed oropharyngeal airway (COPA) with propofol or sevoflurane in adults.

STUDY OBJECTIVES: To compare the respiratory depressant effects of propofol and sevoflurane used to facilitate the placement of the cuffed oropharyngeal airway (COPA), and to evaluate the effectiveness of the COPA in supporting positive pressure ventilation during anesthetic-induced apnea. DESIGN: Randomized, single-blinded study. SETTING: University hospital. PATIENTS: 60 ASA physical status I and II adult patients scheduled for elective surgery with general anesthesia. INTERVENTIONS: Patients were induced either with spontaneous inhalation of 5% sevoflurane or with propofol 2.0 mg/kg intravenously (i.v.) followed by a continuous infusion of 170 micrograms kg-1 min-1. If the propofol patient had a tight jaw in 90 seconds, additional propofol (0.5 mg/kg) was administered and the infusion rate was increased to 200 micrograms kg-1 min-1. The COPA was placed as soon as the jaw was sufficiently relaxed to allow its insertion into the mouth. MEASUREMENTS AND MAIN RESULTS: The median (range) time to the COPA placement were 90 seconds (30 to 150 sec) and 120 seconds (60 to 210 sec) with propofol and sevoflurane, respectively (p = 0.07, Mann-Whitney U-test). Unacceptable responses to the placement (3 or more coughs, vigorous or persistent [> 30 sec] movements) occurred in 23% and 17% of those who received propofol and sevoflurane, respectively, (p = 0.35. Chi-square test). All these responses were easily suppressed by additional doses of the assigned induction drug. After placement of the COPA, 53% (16/30) of the propofol patients had apnea lasting at least 30 seconds. Notably, the positive airway pressure at which a leak occurred in the mouth (pharyngeal leak pressure) was lower during this propofol-induced apnea than after the return of spontaneous breathing [9 (5 to 20) cmH2O vs. 15 (5 to 20) cmH2O, p < 0.01, Wilcoxon's signed-rank test]. In contrast, at no time were the sevoflurane patients apneic, and their pharyngeal leak pressure immediately following the placement was 12 (10 to 20) cmH2O. CONCLUSIONS: Propofol and sevoflurane are equally effective in facilitating the placement of the COPA. However, propofol often induces apnea, which is complicated by a less effective seal of the airway by the COPA against positive pressures. Because sevoflurane induction allows spontaneous respiration to continue and provides an adequate pharyngeal seal immediately following the placement of the COPA, it may be advantageous when apnea is not desired.

Adult↗

Chemical species of organotin compounds in sediment at a marina.

A bottom sediment collected in a marina was analyzed for organotin species, and >20 organotin compounds including biodegraded ones were confirmed by comparison with the synthesized standards using gas chromatography (GC)/mass spectrometry and a GC/atomic emission detection system. Their structures were also determined in comparison with those in a technical grade of tri-n-butyltin chloride (TBTC). Eleven organotin compounds were found in the technical TBTC. Among them, unexpected organotin compounds, such as di-n-butyl(2-ethylhexyl)tin chloride and di-n-butyloctyltin chloride, were identified, although the levels were low. These compounds were also found in the sediment sample. The relationship between organotin compounds in the technical TBTC and those in marine products was also discussed.

Chromatography, Gas↗

Some sulfur-containing metabolites of tri-n-butyltin chloride in male rats.

In an attempt to elucidate metabolic destination of TBTO, sulfur-containing metabolites were investigated in the urine. Tri-n-butyltin chloride (TBTC), tri-n-butyltin oxide (TBTO), and their in vitro metabolites in rat liver microsomal enzyme systems, di-n-butyl(3-hydroxybutyl)tin chloride (T3OH), di-n-butyl(3-oxobutyl)tin chloride (T3CO), dibutyltin dichloride (DBTC), and monobutyltin trichloride (MBTC), were intraperitoneally administered to rats. In particular, administration of T3OH and T3CO gave higher amounts of mercapturic acid derivatives, such as N-acetyl-S-(3-oxobutyl)-L-cysteine (3CO-MA) and N-acetyl-S-(3-hydroxybutyl)-L-cysteine (3OH-MA), than TBTC or TBTO. On the other hand, DBTC and MBTC did not yield measurable amounts of 3CO-MA and/or 3OH-MA. The appearance of organotin metabolites in urine indicates that T3OH, T3CO, and hypothesized secondary metabolites, such as n-butyl(3-hydroxybutyl)(3-oxobutyl)tin chloride, n-butyl(3-hydroxybutyl)(4-hydroxybutyl)tin chloride, etc., are subject to the action of glutathione S-transferase to give mercapturic acid derivatives. These sulfur-containing metabolites (3CO-MA and 3OH-MA) were also found in control rat urine.

Animals↗