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Biomedical subjects

T Nagata

Publications and source records attributed to T Nagata.

At least 37 records · Page 2Linked to original sources

High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia.

BACKGROUND: The pathological diagnosis of interstitial lung diseases (ILD) by surgical lung biopsy is important for clinical decision making. There is a need, however, to use serum markers for differentiating usual interstitial pneumonia (UIP) from other ILD. Surfactant protein (SP)-A, SP-D, KL-6, sialyl SSEA-1 (SLX), and sialyl Lewis(a) (CA19-9) are useful markers for the diagnosis and evaluation of activity of ILD. We have investigated the usefulness of these proteins as markers of UIP. METHODS: Serum and bronchoalveolar lavage (BAL) fluid levels of the above five markers were measured in 57 patients with various forms of ILD (19 with UIP, 12 with non-specific interstitial pneumonia (NSIP), eight with bronchiolitis obliterans organising pneumonia (BOOP), and 10 with sarcoidosis), eight patients with the control disease (diffuse panbronchiolitis (DPB)), and nine healthy volunteers. RESULTS: Serum levels of SP-A, SP-D, and KL-6 in patients with UIP and NSIP were significantly higher than in healthy volunteers. In particular, the serum levels of SP-A in patients with UIP were significantly higher than in patients with NSIP (p<0.0001, mean difference -58.3 ng/ml, 95% confidence interval -81.6 to -35.0), and BAL fluid levels of SP-D in patients with UIP were significantly lower than in patients with NSIP (p=0.01, mean difference 322.4 ng/ml, 95% confidence interval 79.3 to 565.5). CONCLUSION: Serum SP-A levels may be clinically useful as a biomarker to differentiate between UIP and NSIP.

Adult↗

Decreased computed tomographic lung density during exacerbation of asthma.

Recently, it was shown that both mean lung density (MLD) and the relative lung area with an attenuation of <-950 HU (RA950) are related to severity of asthma in nonsmoking asthmatics. The aim of the present study was to examine whether reduced computed tomography (CT) lung density during exacerbation could change after treatment. A cross-sectional study was performed to compare CT lung density in 30 stable asthmatics, 30 unstable asthmatics and 25 control subjects. In order to investigate longitudinally the effect of treatment on decreased CT lung density, 17 asthmatics with an exacerbation were followed at the initiation of treatment and 2 months after relief. The MLD was significantly lower and the RA950 significantly higher in unstable asthmatics than in controls and stable asthmatics. Both MLD and RA950 changed significantly with administration of systemic glucocorticoid therapy. The changes in forced expiratory volume in one second correlated significantly with those in both MLD and RA950. The changes in residual volume also correlated significantly with those in both MLD and RA950. It was concluded that decreased computed tomographic lung density during an asthma exacerbation is at least partially reversible, and changes in mean lung density and the relative lung area with a radiation attenuation of <-950 HU are related to the change in forced expiratory volume in one second and residual volume.

Adult↗

Light and electron microscopic radioautographic studies on macromolecular synthesis in amitotic hepatocytes of aging mice.

The problem on cell divisions whether cells proliferate by mitosis or amitosis has been the heated controversy among many biologists since the late 19th century. We confirmed by extensive experiments since the mid 20th century that all the cells proliferated by mitosis not by amitosis but that amitosis actually existed in some glandular cells such as hepatocytes or pancreatic acinar cells which showed only amitotic nuclear divisions without cytoplasmic division producing binucleate cells in several kinds of experimental animals. We further verified that such amitotic cells did not synthesize macromolecular compounds incorporating macromolecular precursors such as 3H-thymidine for DNA, 3H-uridine for RNA or 3H-leucine for proteins. Recent experiments at the end of 20th century using many groups of aging mice, from fetal day 19 to postnatal month 24, injected with such precursors, amitotic cells and resulting binucleate cells in the hepatocytes were detected by electron microscopic radioautography and compared to mononucleate cells. The results demonstrated that only a few hepatocytes showing amitotic nuclear division were found labelled with the 3 precursors demonstrating DNA, RNA and protein synthesis. However, the numbers of silver grains showing incorporations of labelled precursors in respective amitotic cells were very few. It was clarified that the amitotic cells did not synthesize such macromolecules as mononucleate hepatocytes did. On the other hand, more binucleate cells were found than the amitotic cells. DNA synthesis of mononucleate and binucleate hepatocyte nuclei was observed at perinatal stage and disappeared at adult stage. The labeling index of mononucleate hepatocytes was greater than that of binucleate hepatocytes. RNA and protein syntheses in karyoplasm and cytoplasm in both mononucleate and binucleate cells increased from perinatal stage, reaching the maxima at adult stage then decreased to senescent stage. Grain counts revealed that synthesized RNA and proteins were more in binucleate cells than mononucleate cells at respective aging stages.

Aging↗

Comparison of fuzzy inference, logistic regression, and classification trees (CART). Prediction of cervical lymph node metastasis in carcinoma of the tongue.

OBJECTIVES: In this paper three statistical methods [logistic regression, classification and regression tree (CART), and fuzzy inference] for the prediction of lymph node metastasis in carcinoma of the tongue are compared. METHODS: A retrospective collection of data in 75 patients treated for tongue cancer was carried out at the Clinic and Policlinic for Oral and Maxillo-facial Surgery at the University Hospital of Freiburg in Germany between January 1990 and December 1999; biopsy material was used for laboratory evaluations. Statistical methods for the prediction of lymph node metastasis were compared using ROC curves and accuracy rates. RESULTS: All three methods show similar results for the prediction of lymph node metastasis with slightly superior results for fuzzy inference and CART. A great overlap is apparent in the ROC curves. The best result observed for fuzzy inference and CART was a sensitivity of 79.2% [95% confidence interval: (57.8%; 92.9%)] and a specificity of 86.3% (73.7%; 94.3%); the best result for predictions based on the logistic regression was a sensitivity of 66.7% (44.7%; 84.4%) and a specificity of 80.4% (66.9%; 90.2%). Accuracy rates of fuzzy method and CART were higher [accuracy rate for fuzzy method and CART: 84% (73.7%; 91.4%), for logistic regression method: 73.3%, 95%-CI: (61.9%; 82.9%)]. CONCLUSIONS: From a clinical point of view, the predictive ability of the three methods is not sufficiently large to justify use of these methods in daily practice. Other factors probably on the molecular level are needed for the prediction of lymph node metastasis.

Decision Support Techniques↗

Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy.

BACKGROUND: Distal myopathy with rimmed vacuoles (DMRV) is an autosomal-recessive disorder with preferential involvement of the tibialis anterior muscle that starts in young adulthood and spares quadriceps muscles. The disease locus has been mapped to chromosome 9p1-q1, the same region as the hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases have been suspected to be allelic. Recently, HIBM was shown to be associated with the mutations in the gene encoding the bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). OBJECTIVE: To determine whether DMRV and HIBM are allelic. METHODS: The GNE gene was sequenced in 34 patients with DMRV. The epimerase activity in lymphocytes from eight DMRV patients was also measured. RESULTS: The authors identified 27 unrelated DMRV patients with homozygous or compound-heterozygous mutations in the GNE gene. DMRV patients had markedly decreased epimerase activity. CONCLUSIONS: DMRV is allelic to HIBM. Various mutations are associated with DMRV in Japan. The loss-of-function mutations in the GNE gene appear to cause DMRV/HIBM.

Alleles↗

Intestinal granuloma formation in normal and SCID BALB/c mice infected with Angiostrongylus costaricensis.

We studied the histomorphology of granuloma formation and cytokine production in Angiostrongylus costaricensis-infected immunocompetent and immunodeficient BALB/c mice. Histological examination of the infected intestine showed well developed granulomas in BALB/c mice. In contrast, in SCID mice, clusters of eggs and larvae and a progression of infiltration of inflammatory cells were also observed, but little fibroblastic activity was seen. Analysis of plasma of the infected mice demonstrated a dramatic contrast in the cytokine profile between normal and SCID mice. Normal mice infected with A. costaricensis showed highly elevated plasma IFN-gamma levels at week 3 of infection, but plasma IL-4 remained close to the background levels obtained from non-infected mice. In contrast, the amount of those cytokines in the plasma of SCID animals was little affected by this parasitic infection. These results suggest that Th1-mediated immunity is required for granuloma formation in response to A. costaricensis infection in mice.

Angiostrongylus↗

Expression of the movement protein of Tomato spotted wilt virus in its insect vector Frankliniella occidentalis.

Tomato spotted wilt virus (TSWV) is able to infect both its botanical hosts and its insect vector (thrips). In plant tissue the NS(M) protein of TSWV functions as viral movement protein (MP), aggregating into plasmodesma-penetrating tubules to establish cell-to-cell movement. As upon heterologous expression NS(M) was able to form similar tubules on the surface of insect (Spodoptera frugiperda) cells, we have now investigated the expression and cellular manifestation of this protein in infected thrips tissue. It is shown that NS(M), though detectably expressed in both the L2 larval and adult thrips stages, does not aggregate into tubules, indicating that this requirement is associated to its function as MP in plants, and raising the question if NS(M) has a function at all during the insect life cycle of TSWV.

Animals↗

Overexpression of pyrimidine nucleoside phosphorylase enhances the sensitivity to 5'-deoxy-5-fluorouridine in tumour cells in vitro and in vivo.

5-Fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR), a prodrug of 5-FU, are representative of the chemotherapeutic agents for colorectal adenocarcinomas. Pyrimidine nucleoside phosphorylase (PyNPase) catalyses the conversion of 5'-DFUR to 5-FU, the activated form. Murine adenocarcinoma CT26 cells were transfected with human PyNPase cDNA. The engineered transfectants producing PyNPase augmented the response to 5'-DFUR in vitro and in vivo. Animals were administered by means of intraperitoneal (i.p.) injection, and not orally, in order to obtain a better efficiency of absorption. The tumours of the transfected cells nearly all disappeared, even following treatment with quite a small amount of the anticancer agent. The animals injected with the tranfected cells were protected against subsequent challenge with the parental tumour cell line. These findings demonstrate that PyNPase gene transfection increases the sensitivity to 5'-DFUR, and thereby decreases the toxicity of the agent.

Adenocarcinoma↗

Relationship between perfectionism, personality disorders and agoraphobia in patients with panic disorder.

OBJECTIVE: In earlier reports, we found that perfectionism might be involved in the development and/or maintenance of agoraphobia in panic disorder. The present report extends this work by examining the relationship between perfectionism and comorbidity with personality disorders in panic disorder patients with agoraphobia (PDA) and those without agoraphobia (PD). METHOD: We examined comorbidity of personality disorders by Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and assessed perfectionism using multidimensional perfectionism scale in 56 PDA and 42 PD patients. RESULTS: The PDA group met criteria for at least one personality disorder significantly more often than the PD group. With stepwise regression analyses, avoidant and obsessive-compulsive personality disorders emerged as significant indicators of perfectionism in patients with panic disorder. CONCLUSION: These findings suggest that perfectionism in panic disorder patients may be more common in those with comorbid personality disorders, and may be an important target for preventive and therapeutic efforts.

Adult↗

Vertical transmission of Wolbachia in Tetranychus kanzawai Kishida and Panonychus mori Yokoyama (Acari: Tetranychidae).

The vertical transmission of Wolbachia in two species of spider mite was investigated and compared. One species, Tetranychus kanzawai Kishida, was infected with a modification negative strain of Wolbachia while the other species, Panonychus mori Yokoyama, was infected with a modification positive strain. The infection showed perfect maternal transmission in the laboratory population of T. kanzawai in which Wolbachia-infected females produced infected offspring regardless of whether they mated with infected or uninfected males, and uninfected females produced Wolbachia-free progenies without regard to the infection status of their mating partners. In artificial P. mori populations initiated with 50% infected and 50% uninfected female adults, the infection frequencies among progenies increased with each generation, reaching 100% at the sixth generation in the Sendai population and after the sixth generation in the Toyama population. In another experiment, in which an artificial T. kanzawai population was composed of 50% infected and 50% uninfected female adults, the infection frequency in progeny populations increased very slowly, reaching 62.5% at the 15th generation. The difference in infection frequency in the two spider mites may be due to the different strains of Wolbachia.

Animals↗

Circadian rhythm of melatonin and prostaglandin in modulation of stress-induced gastric mucosal lesions in rats.

BACKGROUND: We previously demonstrated the circadian variation of water-immersion restraint stress (WRS)-induced gastric mucosal lesions in rats. AIM: To investigate the roles of melatonin and prostaglandin in the gastric mucosa in circadian modulation of WRS. METHODS: Fasted rats were subjected to 4-h WRS during both the diurnal and nocturnal phases of a light/dark cycle. Mucosal lesions, serum melatonin concentrations, mucosal generation of prostaglandin E2 (PGE2) and mucosal gene expressions of cyclooxygenase (COX)-1 and -2 were evaluated. RESULTS: Lesion area after 4-h stress during the dark phase was significantly smaller than that in light-phase controls. Serum melatonin concentration in control rats during the light phase was significantly increased 4 h after WRS, but PGE2 generation was decreased by 48% as compared to that in intact mucosa before stress. In the dark phase, melatonin concentration after 4-h WRS was significantly depressed as compared with the control level at the corresponding time. PGE2 concentrations after 4-h WRS in the dark phase were not decreased compared with the control level at the corresponding time, although PGE2 level was significantly lower than that in light-phase controls. Expression of COX-1 and COX-2 mRNA was detected after exposure to stress in both the light and dark phases. CONCLUSION: These results suggest that circadian rhythm has an important role in the formation of stress-induced gastric mucosal lesions in rats. The circadian rhythm of melatonin responses and PGE2 generation may contribute to nocturnal/diurnal rhythmicity of gastric mucosal defences between day and night.

Animals↗

Synthesis and antiherpesvirus activities of 5-alkyl-2-thiopyrimidine nucleoside analogues.

Twenty 5-alkyl-2-thiopyrimidine nucleosides were newly synthesized and examined for antiviral activities against herpes simplex virus (HSV), varicella-zoster virus (VZV) and human cytomegalovirus (HCMV). In this study, 2'-deoxy-5-alkyl-2-thiocytidine analogues had lower 50% effective concentration (EC50) values against HSV-1, and 2'-deoxy-5-alkyl-2-thiouridine analogues showed lower EC50 against VZV than their congeners of arabinoside form. Among the compounds examined, 2'-deoxy-5-ethyl and 5-propyl-2-thiocytidine (TN-53 and TN-54) were most potent and selective anti-HSV compounds. Their EC50s were 0.04 and 0.15 microM, and selectivity indexes were more than 7,215 and 1,849, respectively. On the other hand, 2'-deoxy-5-propyl-2-thiouridine (TN-51), 5-bromovinyl-2-thiouracil arabinoside (TN-65) and 5-styryl-2-thiouracil arabinoside (TN-67) were most potent and selective anti-VZV compounds. Their EC50s were 3.1, 3.8 and 2.6 pM for CaQu strain of VZV, respectively, and 2.1 to 3.0 times lower than that of acyclovir. All 2-thiopyrimidine nucleoside analogues did not show antiviral activities against thymidine kinase (TK) negative strains of HSV-1 and VZV. Only three 2-thiocytosine arabinoside compounds showed marginal anti-CMV activities (EC50s were 57-159 pM). All of the five alkyl-2-thio-pyrimidine nucleoside analogues examined were not cytotoxic to human lymphoblastoid cells (RPM18226) and human embryonic fibroblast cells (MRC-5) at 240 microM (100 microg/ml) or more. Regarding the structure-activity relationship of 5-alkyl-2-thiopyrimidine nucleoside analogues, the following remarks will be noted. Elongation of 5-alkyl chain (methyl to ethyl) of 2-thiocytosine in both deoxyribosyl and arabinosyl nucleosides increased anti-HSV-1 activity but not anti-VZV activity. Furthermore, elongation of the same chain (ethyl to propyl) of 2-thiodeoxyuridine increased anti-VZV activity whereas it did not in the case of 2-thiouracil arabinosides.

Antiviral Agents↗

Microarray analysis of gene expression changes in aging in mouse submandibular gland.

Little is known about the effect of salivary gland function during aging based on gene expression. Recently emerged DNA array technology provides a sensitive, quantitative, rapid approach to the monitoring of the global pattern of gene expression. In this study, we used high-density oligonucleotide arrays to monitor the changes of gene expression levels in the submandibular gland (SMG) by comparing adult mice with elderly adult mice. Of the 1328 genes screened, 160 genes (12.0%) showed more than two-fold changes; 154 (96.3%) of these genes, associated with transcription regulation, transport, signal transduction, and enzymes in the elderly mice, exhibited decreased expression levels. The remaining 6 genes (3.7%) in the elderly mice showed increased expression levels. In mouse SMG, analysis of these data suggests that aging may lead the gene expression to decrease than increase. Thus, DNA array technology can be a powerful tool for the identification of age-associated candidate genes for further analysis in aging.

1-Phosphatidylinositol 4-Kinase↗

Enhanced expression of endothelin-1 and endothelin-converting enzyme-1 in acute hypoxic rat aorta.

Deeply anesthetized male Wistar rats were perfused by Hanks' balanced salt solution bubbled with either 95%air and 5%CO2 (normoxic group) or 95%N2 and 5%CO2 (hypoxic group) from the thoracic aorta for 30 min, and the isolated abdominal aortae from both groups were used for electron microscopy, immunocytochemistry of endothelin (ET)-1 and ET-converting enzyme (ECE)-1, and in situ hybridization of preproET-1 mRNA. A remarkable increase in the number of Weibel-Palade (WP) bodies, storage sites of ET-1 and ECE-1, occurred in the hypoxic group when compared to the normoxic group. Immunoreactivities for ET-1 and ECE-1, and signals for preproET-1 mRNA were seen along the endothelia of both groups, but the intensities were significantly elevated in the hypoxic group. The increase in the number of ECE-1 immunoreactive gold particles was noticed especially in WP bodies in the hypoxic group. These findings indicate the enhancement of preproET-1 synthesis in the aortic endothelial cells as well as the acceleration of ET-1 processing in increased WP bodies in such cells in an experimentally hypoxic condition of the rat aortae.

Acute Disease↗

Association of parvovirus B19 infection with acute glomerulonephritis in healthy adults: case report and review of the literature.

An otherwise healthy 20-year-old woman presented with an erythematous rash on her face as well as arthralgia and anemia. She also had systemic edema, proteinuria and hypertension. Laboratory data on admission showed hypocomplementemia, human parvovirus B 19 (HPV) DNA and both immunoglobulin (Ig) M and IgG antibodies to HPV in her serum. Renal biopsy specimens showed features of endocapillary glomerulonephritis under light microscopy. Electron microscopy showed massive subendothelial electron-dense deposits. No cause was probable other than immune complex-mediated glomerulonephritis associated with HPV infection. In a review of this and similar cases reported in the literature, several characteristic features come to light: female dominance, onset in the second or third decade of life, hypocomplementemia, histologic renal endocapillary and/or mesangioproliferative glomerulonephritis with subendothelial deposits and spontaneous recovery.

Adult↗

Role of glial glutamate transporters in the facilitatory action of FK960 on hippocampal neurotransmission.

We found previously that N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate (FK960) facilitated hippocampal neurotransmission in the dentate gyrus of rat hippocampal slices. The present study was conducted to understand the mechanism underlying the facilitatory action of FK960. The facilitation was inhibited by H-89, an inhibitor of cAMP-dependent protein kinase (PKA), but it was not affected by cycloheximide, a protein synthesis blocker. In cultured rat hippocampal neurons, the drug had no effect on either spontaneous miniature excitatory postsynaptic currents or whole-cell membrane currents evoked by glutamate, kainate, or NMDA, suggesting that the facilitatory action of FK960 is not caused by increasing presynaptic transmitter release or excitatory postsynaptic conductances. FK960 inhibited responses of the glial glutamate transporter, GLT-1, expressed in Xenopus oocytes, and a similar effect was found with cultured rat astrocytes. The FK960 action was inhibited in the presence of H-89. The results of the present study thus suggest that FK960 facilitates hippocampal neurotransmission by inhibiting GLT-1 glial glutamate reuptake via a PKA pathway, thereby increasing synaptic glutamate concentrations.

Amino Acid Transport System X-AG↗