Biomedical subjects

J Nagata

Publications and source records attributed to J Nagata.

At least 19 recordsLinked to original sources

PubMed2003

Adenocarcinoma and multiple adenomas of the large intestine, associated with Cronkhite-Canada syndrome.

The Cronkhite-Canada syndrome is a rare non-hereditary disorder with generalised gastrointestinal polyposis, associated with ectodermal changes. We report here a case of adenocarcinoma and multiple adenomas of the large intestine associated with Cronkhite-Canada syndrome in a 61-year-old Japanese man. Histologically, the rectal tumour was composed of well-differentiated tubular adenocarcinoma, admixed with foci of adenomatous components, and associated with hyperplastic mucosa of Cronkhite-Canada syndrome. Multiple polyps, >20 polyps < or = 2.0 cm in diameter, were found near the carcinoma of the resected rectum. Histologically, superficial parts of the polyps were composed of tubular adenomas, and basal parts of the polyps were hyperplastic dilated glands. It was speculated that, in the present case, the rectal adenocarcinoma arose from mucosal hyperplasia (Cronkhite-Canada polyp)-adenoma-carcinoma pathway. This suggested that Cronkhite-Canada syndrome has definite malignant potential, although the frequency of malignant transformation is thought to be low in Cronkhite-Canada syndrome.

Adenocarcinoma↗

PubMed2001

Reversal of cisplatin and multidrug resistance by ribozyme-mediated glutathione suppression.

gamma-Glutamylcysteine synthetase (gamma-GCS) is a key enzyme in glutathione (GSH) synthesis, and is thought to play a significant role in intracellular detoxification, especially of anticancer drugs. Increased levels of GSH are commonly found in the drug-resistant human cancer cells. We designed a hammerhead ribozyme against gamma-GCS mRNA (anti-gamma-GCS Rz), which specifically down-regulated gamma-GCS gene expression in the HCT-8 human colon cancer cell line. The aim of this study was to reverse the cisplatin and multidrug resistance for anticancer drugs. The cisplatin-resistant HCT-8 cells (HCT-8DDP cells) overexpressed MRP and MDR1 genes, and showed resistance to not only cisplatin (CDDP), but also doxorubicin (DOX) and etoposide (VP-16). We transfected a vector expressing anti-gamma-GCS Rz into the HCT-8DDP cells (HCT-8DDP/Rz). The anti-gamma-GCS Rz significantly suppressed MRP and MDR, and altered anticancer drug resistance. The HCT-8DDP/Rz cells were more sensitive to CDDP, DOX and VP-16 by 1.8-, 4.9-, and 1.5-fold, respectively, compared to HCT-8DDP cells. The anti-gamma-GCS Rz significantly down-regulated gamma-GCS gene expression as well as MRP/MDR1 expression, and reversed resistance to CDDP, DOX and VP-16. These results suggested that gamma-GCS plays an important role in both cisplatin and multidrug resistance in human cancer cells.

Antineoplastic Agents↗

PubMed2001

Spontaneous arterial baroreflex control of the heart rate during head-down tilt in heat-stressed humans.

The purpose of this study was to elucidate the effect of raised body temperature per se during acute heat stress on the spontaneous arterial baroreflex control of heart rate (fc) in humans. To investigate whether unloading of cardiopulmonary baroreceptors during whole-body heating would alter the arterial baroreflex control of fc, we controlled loading of the cardiopulmonary baroreceptors by head-down tilt (HDT) at angles of 5 degrees, 10 degrees, 15 degrees, and 30 degrees during heat stress produced by hot-water-perfused suits. The sensitivity of the arterial baroreceptor-cardiac reflex was calculated from the spontaneous changes in beat-to-beat arterial pressure and fc. As an index of cardiopulmonary baroreceptor loading, the left atrial diameter (LAD) was measured by echocardiography. During whole-body heating, the LAD decreased with the rising body core temperature and increased with the HDT. The decreased LAD during heating almost recovered to the normothermic control level by 10 degrees HDT. In the supine position, cardiac baroreflex sensitivity remained unchanged during heating. Arterial pressure, fc and cardiac baroreflex sensitivity were not changed by HDT ranging from 5 degrees to 30 degrees during heating. These results suggest that cardiac baroreflex sensitivity remain unchanged during graded loading of the cardiopulmonary baroreceptors in heat-stressed humans. Also, we conclude that the sensitivity of the spontaneous arterial baroreflex controlling the fc is not influenced by raised body temperature per se during acute heat stress.

Adult↗

PubMed2001

Effects of water-soluble hemicellulose from soybean hull on serum antibody levels and activation of macrophages in rats.

Effects of soybean hull water-soluble hemicellulose (WSHC) on serum immunoglobulin (Ig) concentration and production of NO and IL-1beta from peritoneal macrophages were examined and compared with those of Agaricus blazei in the rat system. WSHC consisted of arabinose, galactose, xylose, glucose, and rhamnose, and the molecular weight was approximately 500000. Rats were ip administrated each sample at a dose of 0.67, 13.4, or 26.9 mg/kg/day for 14 days. The administration of WSHC resulted in significantly higher productions of IgM (p < 0.01 on day 6, p < 0.05 on day 14) and IgG (p < 0.05 on day 6) than those in other groups. When peritoneal macrophages were stimulated with various concentrations of sample (0.67, 13.4, or 26.9 mg/mL), WSHC significantly increased both NO and IL-1beta productions only at the concentration of 13.4 (mg/mL) compared with those of a saline group. These findings demonstrate that WSHC enhances humoral immunity and activation of macrophages, thereby leading to the augmentation of immune responses in rats.

Agaricus↗

PubMed2001

Bottlenecks, drift and differentiation: the population structure and demographic history of sika deer (Cervus nippon) in the Japanese archipelago.

We assessed genetic differentiation and diversity in 14 populations of sika deer (Cervus nippon) from Japan and four populations of sika deer introduced to the UK, using nine microsatellite loci. We observed extreme levels of differentiation and significant differences in diversity between populations. Our results do not support morphological subspecies designations, but are consistent with previous mitochondrial DNA analyses which suggest the existence of two genetically distinct lineages of sika deer in Japan. The source of sika introduced to the UK was identified as Kyushu. The underlying structure of Japanese populations probably derives from drift in separate glacial refugia and male dispersal limited by distance. This structure has been perturbed by bottlenecks and habitat fragmentation, resulting from human activity from the mid-nineteenth century. Most current genetic differentiation and differences in diversity among populations probably result from recent drift. Coalescent model analysis suggests sika on each of the main Japanese islands have experienced different recent population histories. Hokkaido, which has large areas of continuous habitat, has maintained high levels of gene flow. In Honshu the population is highly fragmented and is likely to have been evolving by drift alone. In Kyushu there has been a balance between gene flow and drift but all the populations have experienced high levels of drift. Habitat fragment size was not significantly associated with genetic diversity in populations but there was a significant correlation between habitat fragment size and effective population size.

Alleles↗

PubMed2001

Embolization of the left portal vein to inferior vena cava shunts for chronic recurrent hepatic encephalopathy via the mesenteric vein.

Diagnostic imaging and embolization therapy for very rare intrahepatic portal-systemic shunts with liver cirrhosis are reported. An 82-year-old woman was admitted to the hospital (Yachiyo Hospital) because of hepatic encephalopathy. Computed tomography with contrast enhancement demonstrated anomalous vessels between the portal vein and the inferior vena cava. Those shunts were suspected as the cause of her encephalopathy with hyperammonemia. Portography through McBurney's laparotomy demonstrated two portal-caval shunts; one was from the bifurcation of the portal vein and the other was from the left portal vein. They seemed to originate from the vascular system of the caudate lobe, and were obstructed with stainless coils. The patient is well with a normal serum ammonia level 40 months following the intervention.

Aged↗

PubMed2001

Interleukin 10 expression is correlated with thrombospondin expression and decreased vascular involvement in colon cancer.

Interleukin 10 (IL-10) is an immuno-suppressive cytokine produced by T-lymphocytes, and a regulatory molecule for angiogenesis in various cancers. We examined IL-10 gene expression in 53 colon cancer patients who underwent surgical resection. IL-10 gene expression was correlated with TSP1 and TSP2 gene expression (P=0.0049, P=0.0285). Colon cancer with IL-10 gene expression (19/53) showed significantly decreased venous involvement (P=0.0433). The mean vessel counts in the colon cancers with IL-10 gene expression were significantly lower than those without IL-10 gene expression (P<0.001). These results suggested that IL-10 stimulates angiostatic factor gene expression, and results in suppression of venous involvement.

Adenocarcinoma↗

PubMed2001

Significant correlation between interleukin 10 expression and vascularization through angiopoietin/TIE2 networks in non-small cell lung cancer.

The expression of interleukin 10 (IL-10) is correlated with clinical prognosis in non-small cell lung cancer [NSCLC (H. Hatanaka et al., ANN: ONCOL:, 11: 815--819, 2000)]. However, the effects of IL-10 expression on vascularization in NSCLC are not apparent. We examined the gene expression of IL-10/IL-10 receptor and various angiogenic/angioinhibitory factors in 95 NSCLC samples to determine the correlation between IL-10 production and vascularization. Vascular endothelial growth factor, angiopoietin [Ang (Ang-1 and Ang-2)], thrombospondin, brain-specific angiogenesis inhibitor 1, vascular endothelial growth factor receptors (KDR and flt-1), and Ang receptor (TIE2) gene expression were evaluated by reverse transcription-PCR. The cellular localization of these factors and vascularity in the cancer stroma were examined immunohistochemically. Seventy-eight (82.1%) and 93 (97.9%) of these 95 NSCLCs were positive for IL-10 and IL-10 receptor, respectively. Ang-1, Ang-2, and TIE2 gene expression was seen in 76 (97.4%), 73 (93.6%), and 78 (100%) of 78 IL-10-positive NSCLCs, respectively, and was significantly correlated with IL-10 gene expression (P < 0.0088, <0.0008, and 0.0305, respectively; Fisher's exact method). The localizations of Ang-1, Ang-2, and TIE2 were confirmed within tumor cells immunohistochemically. Vascular number and measurement area were significantly higher in the IL-10-positive NSCLCs (33.500 +/- 9.299/microm(2) and 4.742 +/- 1.287%) as compared with IL-10-negative NSCLCs (10.611 +/- 2.839/microm(2) and 0.718 +/- 0.331%; Mann-Whitney U test, P = 0.0039). The IL-10 expression did not show any significant correlation with the expression of other factors. These results suggested that tumor-produced IL-10 promotes stromal vascularization through expression of Ang-1, Ang-2, and TIE2.

Angiogenesis Inhibitors↗

PubMed2000

Clinical implications of interleukin (IL)-10 induced by non-small-cell lung cancer.

BACKGROUND: The type 2 cytokine interleukin (IL)-10 has been reported to inhibit the antitumour activity of the regional immunity against various neoplasms. Certain lung cancers produce IL-10, but the clinical significance of IL-10 expression is not well understood. PATIENTS AND METHODS: We examined IL-10 and IL-10 receptor (IL-10R) mRNA expression in 82 non-small-cell lung cancers (NSCLC) by reverse transcription-polymerase chain reaction (RT-PCR) assay. Immunohistochemistry (IHC) and enzyme immunoassay (EIA) were applied to evaluate the cellular localisation and the serum levels of IL-10. RESULTS: RT-PCR assay revealed IL-10 mRNA expression in 68 (83%) of 82 NSCLC surgical specimens (40 of 50 adenocarcinomas, 22 of 26 squamous cell carcinomas, 5 of 5 large-cell carcinomas, 1 of 1 adenosquamous-cell carcinoma). RT-PCR assay also revealed IL-10R mRNA expression in 79 cases of NSCLC (96.1%). IL-10 expression was confirmed within tumour cells by IHC. EIA showed no significant serum IL-10 elevation in the 12 NSCLC positive for IL-10 mRNA expression (0-2.99 pg/ml). The NSCLC patients with IL-10 production showed significantly poorer prognosis than those without IL-10 production (P < 0.05, Kaplan Meier, log-rank test). CONCLUSIONS: These results suggested that the cytoplasmic IL-10 correlated to clinical prognosis, and that IL-10 expression is a prognostic factor for NSCLC.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Hammerhead ribozyme specifically inhibits vascular endothelial growth factor gene expression in a human hepatocellular carcinoma cell line.

Hammerhead-type ribozymes are often utilized to suppress the expression of target genes. We evaluated the efficacy of an anti-vascular endothelial growth factor (VEGF) hammerhead-type ribozyme against GUC at exon 1 of the VEGF gene in a cell-free system (in vitro) as well as in the hepatocellular carcinoma cell line HLF (in vivo). The anti-VEGF ribozyme (alphaVRz) specifically cleaved synthetic VEGF RNA substrate, but not other triplet sequences of VEGF RNA substrate in vitro. When the alphaVRz was introduced into HLF cells, the ribozyme suppressed not only VEGF mRNA level but also that of VEGF protein. These results suggest that this ribozyme selectively inhibits VEGF gene expression in human hepatocellular carcinoma cells.

Base Sequence↗

PubMed2000

Hyoid position, pharyngeal airway and head posture in relation to relapse after the mandibular setback in skeletal Class III.

This study evaluates the process of relapse after mandibular setback surgery by an analysis of the role of craniofacial morphology, hyoid position, pharyngeal airway and head posture. Subjects examined were 62 patients who received the sagittal split ramus osteotomies (SSRO). Changes of the craniofacial and related structures were evaluated from the serial cephalograms up to 3 years after the surgery. Results indicated that mandibular relapse represented by Pg occurred mostly within 6 months after the surgery. A net setback of the mandible was 9.1 mm and the superior move was 1.7 mm, with a reduction of 7.2 mm in mandibular length, 4.2 mm in ramus height, 3.7 mm in posterior face height, 2.6 degrees in gonial angle, an increase of 2.9 degrees in mandibular plane angle (MPA) by the last examination. Hyoid bone moved backward and downward and head posture was raised. The forward relapse of Pg was correlated with the changes of ANB, MPA, ramus height and hyoid position. Only hyoid position was predictably correlated with mandibular morphology and head posture. These findings suggest that mandibular setback alters the relationship among the hyoid position, pharyngeal airway and the head posture. It might be critical, therefore, relapse is closely monitored and controlled before the full healing of fragments and new muscular balance is established.

Journal Article↗

PubMed2000

Hyoid position, pharyngeal airway and head posture in relation to relapse after the mandibular setback in skeletal Class III.

Journal Article↗

PubMed1999

Two genetically distinct lineages of the sika deer, Cervus nippon, in Japanese islands: comparison of mitochondrial D-loop region sequences.

To investigate genetic diversity among populations of the sika deer, Cervus nippon, nucleotide sequences (705-824 bases) of the mitochondrial D-loop regions were determined in animals from 13 localities in the Japanese islands. Phylogenetic trees constructed by the sequences indicated that the Japanese sika deer is separated into two distinct lineages: the northern Japan group (the Hokkaido island and most of the Honshu mainland) and the southern Japan group (a part of the southern Honshu mainland, the Kyushu island, and small islands around the Kyushu island). All sika deer examined in this study shared four to seven units of repetitive sequences (37 to 40 bases each) within the D-loop sequences. The number of tandem repeats was different among the populations, and it was specific to each population. Six or seven repeats occurred in populations of the northern Japan group, while four or five repeats occurred in populations of the southern Japan group. Each repeat unit included several nucleotide substitutions, compared with others, and 26 types were identified from 31 animals. Sequences of the first, second, and third units in arrays were clearly different between the northern and the southern groups. Based on these D-loop data, colonization and separation of the sika deer populations in the Japanese islands were estimated to have occurred less than 0.5 million years before present. Our results provide an invaluable insight into better understanding the evolutionary history, phylogeny, taxonomy, and population genetics of the sika deer.

Animals↗

PubMed1999

Immunohistochemical evaluation of the marbled state in childhood hypoxic encephalopathy.

We have immunohistochemically analyzed the marbled state in 8 cases of perinatal hypoxic ischemic encephalopathy and 4 cases of infantile hypoxic encephalopathy, using antibodies against calbindin-D28k (CaBD), glial fibrillary acidic protein (GFAP), methionine-enkephalin (MEnk), myelin basic protein (MBP), neurofilament (NF), parvalbumin (PV), substance-P (SuP) and synaptophysin (SP). The marbled state was found in the thalamus in 11 cases, whose age at death was over 10 years. Four cases demonstrated the marbled state in the cerebral cortex, in addition to the striatum and/or the thalamus. The abnormally myelinated fibers in the marbled state were stained with both Kluver-Barrera and Holzer stainings; however, they were partly immunopositive for MBP and completely immunonegative for GFAP, CaBD, MEnk, PV, SuP and SP, although some of the neurons and/or fibers showed immunoreactivities for those calcium-binding proteins and/or neurotransmitters. The axons were visualized in the abnormally myelinated fibers by Bodian staining and/or anti-NF immunostainings in the cerebral cortex and striatum but not in the thalamus. GFAP-positive astrocytes did not show any continuity with the abnormally myelinated fibers. These histological features were seen in the cerebral cortex, striatum and thalamus. Difference of the etiology did not affect the histological features with the exception of anti-PV staining, in which PV-immunopositive neurons were observed only in aged subjects with infantile hypoxic encephalopathy, and seemed to be more severely affected by hypoxic stress during the perinatal period than the early infantile period. These data suggest that the site of lesion or the length of survival period after brain injury might influence the formation of the marbled state rather than the etiology. And the direct relationship between the abnormally myelinated fiber and astrocytic process was not verified.

Adolescent↗

PubMed1999

Percutaneous bowel drainage for jaundice due to afferent loop obstruction following pancreatoduodenectomy: report of a case.

A case of jaundice due to an obstruction of the afferent loop following a pancreatoduodenectomy is presented. The dilated loop of the jejunum was drained percutaneously with a 12-F gastrostomy tube. Localized peritonitis around the puncture site was managed conservatively and the obstructive jaundice improved. The treatment strategy for this type of jaundice is discussed.

Afferent Loop Syndrome↗

PubMed1999

Increased heterogeneity of chromosome 17 aneuploidy in endometriosis.

OBJECTIVE: Endometriosis is a complex gynecologic disorder that may display features similar to malignancy, including aggressive growth and localized invasion of the myometrium or spread to various organs outside the uterus. Molecular studies of cancer have demonstrated that genomic instability involving chromosome 17 plays a role in the development and progression of various tumor types. These involve gain and/or loss, deletions, and mutations of candidate tumor suppressor genes (eg, BRCA1 and p53 ) on chromosome 17. STUDY DESIGN: We used a 2-color fluorescence in situ hybridization method for analysis of endometriotic and normal archival tissue. Centromere-specific and locus-specific p53 probes localized to chromosome 17 were selected to study 8 patients with late-stage (severe) endometriosis. Single cells localized to endometriotic lesions or normal endometrial glands were analyzed and identified as normal or abnormal on the basis of the distribution of fluorescence in situ hybridization signals. RESULTS: Overall, chromosome 17 aneuploidy was significantly greater (P <.05) in the endometriosis specimens (mean of 65%) than in normal endometrial cells (mean of 25%). No significant difference (P =.1071) in the distribution of fluorescence in situ hybridization signals was observed among the 5 normal endometrial specimens. However, significant differences (P <. 0001) were observed between the 8 endometriosis tissue specimens. CONCLUSION: We found increased heterogeneity of chromosome 17 aneuploidy in endometriosis. These findings support a multistep pathway involving somatic genetic alterations in the development and progression of this common disease.

Aneuploidy↗

PubMed1999

Pathological study on sibling autopsy cases of the late infantile form of neuronal ceroid lipofuscinosis.

We report autopsy cases of two brothers with the late infantile form of neuronal ceroid lipofuscinosis (LINCL) and examine apoptotic cell death in autopsied brains. Both patients showed psychomotor developmental delay, cerebellar ataxia, convulsions, visual disturbance and myoclonus, and they became bedridden around the age of 6-7 years. Macular changes, mimicking cherry-red spots, were observed on funduscopy, but conjunctival biopsy failed to disclose storage materials. In these cases, the autopsies demonstrated severe atrophy with neuronal loss and gliosis throughout the brain and spinal cord, except the hypothalamic neurons and motor neurons in the brain-stem and spinal cord, and autofluorescent lipofuscin-like materials of two types, fine granular deposits and coarse round bodies, were stored in the remaining neurons and glial cells, and in the epithelial cells of various visceral organs. Immunostaining for mitochondrial subunit C visualized the fine granular deposits but not the coarse round bodies. The nuclei of neurons and glia cells were stained by in situ nick end labeling, which was more pronounced in the younger case, although the expression of both bcl-2 and bcl-x was not significantly altered in these cases. It is suggested that immunohistochemistry for subunit C may be useful for diagnosis of NCL, and further investigations are necessary to clarify the relationship between LINCL and apoptosis, especially in severely affected cases.

Atrophy↗

PubMed1998

Megalencephaly, hydrocephalus and cortical dysplasia in severe dwarfism mimicking leprechaunism.

This report concerns an autopsy case of megalencephaly exhibiting a unique combination of physical and brain malformations. A 4-year-old boy had a peculiar face, a severe reduction of subcutaneous adipose tissue, severe growth failure and frequent hypoglycemic episodes. These clinical features were compatible with leprechaunism; however, the absence of hyperinsulinemia and insulin resistance prevented the diagnosis of leprechaunism. The autopsy disclosed complex cardiac and brain malformations. Although hydrocephalus coexisted, the brain weight after complete removal of the cerebrospinal fluid was 2260 g, which was greater than the average brain weight of normal Japanese children of the same age. The neuronal density in the cerebral cortex was decreased, while the surface area of the cerebral cortex and white matter were greater than those in an age-matched control. There was cortical dysplasia in the frontal and parietal lobes. Endocrine tests and immunohistochemical analysis of the brain did not demonstrate any abnormalities in the hypothalamus-pituitary system. Megalencephaly can be associated with dwarfism, and this case is important for consideration of the interrelationship between neuronal proliferation and physical growth.

Brain↗