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Biomedical subjects

K Inada

Publications and source records attributed to K Inada.

At least 91 records · Page 5Linked to original sources
PubMed1997

Rare occurrence of ras and p53 gene mutations in mouse stomach tumors induced by N-methyl-N-nitrosourea.

The incidence of point mutations of H-, K- and N-ras and p53 oncogenes in male BALB/c mouse stomach tumors induced with N-methyl-N-nitrosourea (MNU) was examined by direct sequencing and PCR single-strand conformation polymorphism (PCR-SSCP). A mutation of GGT to AGT at K-ras codon 12 was found by SSCP in one adenocarcinoma from a total of 19 specimens including 5 adenocarcinomas, 9 adenomatous hyperplastic regions, 1 squamous cell carcinoma and 4 normal-like stomach regions from 4 mice. No mutations were detected by direct sequencing of H-, K- and N-ras oncogenes at exons 1 (codons 12 and 13) and 2 (codon 61) in a total of 26 specimens comprising 10 adenocarcinomas, 10 adenomatous hyperplastic regions, 2 squamous cell carcinomas and 4 normal-like stomach regions from 6 mice. No mutations were detected by direct sequencing of p53 oncogene at exons 5, 6, 7 and 8 in a total of 30 specimens including 13 adenocarcinomas, 8 adenomatous hyperplastic regions, 2 squamous cell carcinomas, 1 papilloma and 6 normal-like stomach regions from 7 mice. These results suggest that ras and p53 oncogenes do not play a role in mouse stomach carcinogenesis induced by MNU.

Adenoma↗
PubMed1997

Gastric and intestinal mixed and solely intestinal types of intestinal metaplasia in the human stomach.

To generate a novel understanding of intestinal metaplasia (IM) on the basis of cellular differentiation status, a total of 132 gastric surgical specimens were studied using gastric and small intestinal cell markers by mucin histochemical and immunohistochemical techniques. The cases were divided into two types: (i) gastric and intestinal (GI) mixed type; and (ii) solely intestinal (I) type, with the reference to the presence of gastric and/or intestinal cell markers. The GI mixed type was subdivided into six subtypes: (I) a subtype consisting of surface mucous (Su), pyloric gland (Py), intestinal absorptive (Ab), and goblet (Go) cells, but lacking Paneth (Pa) cells, GI(Pa-); (ii) a GI(Pa-) subtype without Py cells, GI(Py-, Pa-); (iii) a GI(Pa-) subtype without Su cells, GI(Su-, Pa-); (iv) a GI(Su-, Pa-) subtype with Pa cells, GI(Su-, Pa+); (v) a GI(Pa-) subtype with Pa cells, GI(Pa+); and (vi) a GI(Pa+) subtype without Py cells, GI(Py-, Pa+). The I type was subdivided into: (i) a subtype consisting of cells with Ab and Go cells, I(Pa-); and (ii) a I(Pa-) subtype with Paneth cells, I(Pa+). The GI mixed subtypes, except for the GI(Py-, Pa-) and GI(Py-, Pa+), were characterized by intestinalized gastric pits connected with underlying pyloric glands. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) revealed a common proliferative cell zone between the two. The GI mixed type, especially the GI(Pa-) subtype, predominated in the pyloric mucosa, while the I type was most frequent in the fundic region, suggesting that the pathogenesis of IM differs between these two locations. The results of the study confirm that IM is an abnormal and unstable differentiation status between the stomach and small intestine.

Adult↗
PubMed1997

A case of congenital Listeria septicemia associated with high levels of inflammatory cytokines.

A case of congenital Listeria septicemia is reported. A 2256 g male infant suffering from respiratory and circulatory failure with shock-like symptoms and high levels of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, -6, and -8), was admitted to the Morioka Red Cross Hospital. Listeria monocytogenes was cultured from cord blood, contents from the external ear canal, rectum and stomach. The infant was treated with surfactant replacement as well as conventional therapy. The high levels of interleukin-1 beta decreased with the improvement of the circulatory function, which might have been the major cause of the poor clinical state.

Cytokines↗
PubMed1997

Elevation of serum interleukin-1 receptor antagonist levels in women with gynaecological cancers.

This study included 15 patients with gynaecological cancers (7 with cervical cancer, 6 with endometrial cancer, and 12 with ovarian cancer); 7 with benign gynaecological disorders (5 with benign ovarian tumour and 2 with uterine myoma); and 10 healthy women as a control group. Serum interleukin-1 receptor antagonist (IL-1 ra) levels in patients with gynaecological cancer were significantly higher than those in patients with benign gynaecological disorders (P = 0.04) and in healthy controls (P = 0.0009). IL-1 ra may play an important role in host immune responses in local and general environments against gynaecological cancers.

Endometrial Neoplasms↗
PubMed1997

Interleukin-4, interleukin-10, and soluble tumor necrosis factor receptors in cord blood.

OBJECTIVE: We assessed cord blood for levels of interleukin-4 (IL-4), interleukin-10 (IL-10), and p55 (sTNFR-I) and p75 (sTNFR-II) soluble tumor necrosis factor receptors. STUDY DESIGN: Umbilical cord IL-4, IL-10, tumor necrosis factor alpha (TNF alpha), sTNFR-I, and sTNFR-II were measured in 21 normal appropriately grown newborns delivered vaginally (normal pregnancy), and 3 abnormal pregnancies (1 preterm delivery, 1 premature rupture of membranes with chorioamnionitis, and 1 abruptio placentae with fetal and neonatal distress). Umbilical cord arterial blood pH and PO2 were also measured. RESULTS: The TNF alpha, sTNFR-I, and sTNFR-II were detectable in all cord blood samples in normal pregnancies. IL-4 was detected in 10 of 21 samples (47.6%), and IL-10 was undetectable in normal pregnancies. IL-10 could be detected in the cases with chorioamnionitis and abruptio placentae. Soluble tumor necrosis factor receptors in the case with preterm delivery and the case with abruptio placentae were elevated compared with the levels in control samples. CONCLUSION: Both the p55 and p75 soluble tumor necrosis factor receptors are physiologic constituents of term cord blood. An immunosuppressive role of IL-10 and a protective role of soluble tumor necrosis factor receptors are suggested in abnormal pregnancies. However, in view of the small number of abnormal pregnancies, these observations must be considered preliminary.

Abruptio Placentae↗
PubMed1997

Immunoelectron microscopic demonstration of regulated pathway for calcitonin and constitutive pathway for carcinoembryonic antigen in the same cells of human medullary carcinomas of thyroid glands.

The human medullary carcinomas are well known to secrete calcitonin (CT) as a neuroendocrine peptide and carcinoembryonic antigen (CEA) as a serum protein that is integrated into the cell membrane. This ultrastructural study is designed to elucidate whether CT and CEA are secreted via two different intracellular secretory pathways, a regulated pathway and a constitutive pathway. The immunoelectron microscopic postembedding method, performed on four cases of the human medullary carcinomas of the thyroid using plastic embedding material, disclosed two distinct different localization patterns for CT and CEA. CT was localized exclusively in dense cored secretory granules. CEA was present in the cell membrane and in the secretory vesicles. The secretory granules were completely negative for CEA. The trans-Golgi networks were also positive for CT and CEA. Electron microscopic double staining confirmed these localization in the same carcinoma cells. These observations suggest the presence of two distinct pathways in the endocrine cancer cells, i.e., the regulated pathway for CT and the constitutive pathway for CEA.

Biological Transport↗
PubMed1997

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

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

Adolescent↗
PubMed1997

Anti-inflammatory cytokine levels in patients with septic shock.

We measured the plasma levels of anti-inflammatory cytokines, including interleukin 1 receptor antagonist (IL-1ra), IL-4 and IL-10; inflammatory cytokines, including IL-2, IL-6, IL-8 and tumor necrosis factor receptor I and II (TNFR I and TNFR II); and endotoxin in 11 patients with septic shock associated with gram-negative bacteria and 12 patients with sepsis not associated with shock. The plasma levels of IL-1ra and IL-10 were elevated in the septic shock group compared with the sepsis group. TNFR I and TNFR II levels tend to be higher in the septic shock group. The plasma level of TRNF-alpha was significantly correlated with levels of IL-1ra, IL-4, IL-10, TNFR I, and TNFR II. The elevated levels of the anti-inflammatory cytokines, TNFR I, and TNFR II, appeared to reflect an attempt to suppress the shock syndrome.

Adult↗
PubMed1997

Assessment of inflammatory cytokines, nitrate/nitrite, type II phospholipase A2, and soluble adhesion molecules in systemic inflammatory response syndrome.

Plasma endotoxin levels, nitrate/nitrite (NOx), type II phospholipase A2 (PLA2), soluble adhesion molecules, and inflammatory cytokines were measured in 34 patients with systemic inflammatory response syndrome (SIRS). Significant correlations were found between NOx values, PLA2 values, soluble adhesion molecules, and inflammatory cytokines, suggesting the possibility that these factors were deeply affected each other. When the 34 SIRS patients were divided into the group with sepsis (n = 20) and with the group with trauma without documented infection (n = 14), despite the fact that the difference in APACHE II scores was not significant, all of the factors except endotoxin were significantly higher in the sepsis group than in the trauma group, and the outcome was death in 4 of the 14 patients in the trauma group (28.6%), as opposed to 14 of the 20 patients in the sepsis group (70.0%). The mediator values measured in this study seemed to reflect the difference in the severity of the patients' disease and their outcome.

Adult↗
PubMed1996

Age-related increase in nitric oxide synthase activity in senescence accelerated mouse brain and the effect of long-term administration of superoxide radical scavenger.

The levels of nitric oxide (NO) and NO synthase (NOS) activities were compared in the brains of young adult (3 months old), aged (11 months old) and TJ-960 administered (11 months old) senescence accelerated mice (SAM), of which the SAMP8 substrain is inferior in acquisition of learning due to the abnormality of glutamatergic neurotransmission in the cerebral cortex. TJ-960, which is based on the Kampo (Japanese traditional herbal medicine) prescription Sho-saiko-to-go-keishi-ka-shakuyaku-to, acts as a superoxide radical scavenger and attenuates the deterioration of neuronal activity associated with aging. We administered TJ-960 orally for 5 months. In the cerebral cortex of aged SAMP8, NOS activity was increased compared with that of young adult SAMP8. Though TJ-960 did not alter the contents of NO in any brain region compared with those in aged SAMP8, it did prevent the increase in NOS activity in the aged cerebral cortex. Our data suggest that NOS activity may increase to compensate for the reduced sensitivity of the NO reaction system in the aging process, and that TJ-960 may normalize this increased NOS activity in the cerebral cortex, although further work is clearly needed to ascertain maintenance in the acquisition of learning.

Administration, Oral↗
PubMed1996

p53 mutations in transitional cell carcinomas of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Involvement of p53 gene alterations has been demonstrated in a variety of human neoplasias including urinary bladder carcinomas. N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis models in rodents have been widely used to study carcinogenic processes in this organ. In the present study, transitional cell carcinomas induced in the urinary bladders of male F344 rats treated with 0.05% BBN for 16 or 32 weeks and then sacrificed at experimental week 32 were analyzed for mutational changes in the p53 and H-ras genes by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and subsequent DNA sequencing. The total p53 mutation incidences were 3/10 (30%) and 8/12 (66.7%) in rats treated with BBN for 16 weeks followed by 16 weeks' non-treatment, or in rats treated with BBN for 32 weeks, respectively, while the H-ras mutation incidences were 0/10 (0%), and 1/12 (8.3%), respectively. The present results indicate that mutations in the p53 gene might be involved in the process of urinary bladder carcinogenesis by BBN as part of a multistep pathway. However, considering the decreasing tendency in lesions with p53 mutations after stopping BBN administration, a p53 mutation alone would not appear to be sufficient to give a marked selective advantage to mutant cells. No evidence of H-ras mutation involvement was gained even for the late course of rat urinary bladder carcinogenesis.

Animals↗
PubMed1996

Primary monoclonal and secondary polyclonal growth of colon neoplastic lesions in C3H/HeN<-->BALB/c chimeric mice treated with 1,2-dimethylhydrazine immunohistochemical detection of C3H strain-specific antigen and simple sequence length polymorphism analysis of DNA.

To determine the clonality and cellular origin of colon pre-neoplastic and neoplastic lesions, C3H/HeN<-->BALB/c chimeric mice treated with 1,2-dimethylhydrazine (DMH) were investigated immunohistochemically using a specific antibody to C3H strain-specific antigen (CSA) enabling immunohistochemical discrimination of C3H cells in histological sections of chimeric mouse tissues. To confirm the results of immunostaining, simple sequence length polymorphism (SSLP) analysis was performed on DNA samples extracted from histological sections of adenocarcinomas. C3H/HeN<-->BALB/c chimeric mice were produced by an aggregation procedure and together with BALB/c and C3H/HeN animals were given weekly s.c. injections of 20 mg/kg body weight DMH for up to 20 weeks. At weeks 20 and 35 animals were killed and autopsied. In normal colonic mucosa of the chimeras, each gland was composed entirely of either CSA-positive or -negative cells and no mixed glands were found. Cells of all focal atypias in chimeric mice were, in each case, homogeneous for one or another of the parental types. Of 91 adenomas in chimeric mice, only one comprised both types of cell. Among 119 adenocarcinomas, 12 contained cells of both parental types. In these tumors, however, the 2 phenotypes were not mixed together at random but arranged in discrete areas, with intermingling limited to the junctions. SSLP analysis demonstrated DNAs extracted from CSA-positive and -negative tumors to exhibit the polymorphic patterns of C3H and BALB/c, respectively, while mixed CSA-positive and -negative tumors showed mixtures of both polymorphic DNA types.

1,2-Dimethylhydrazine↗
PubMed1996

Quantitative analysis of vascular endothelial growth factor in primary breast cancer.

BACKGROUND: Recent clinical studies have demonstrated that tumor angiogenesis is a potent prognostic indicator for breast cancer patients. The quantitation of endothelial growth factors is thought to be useful to assess angiogenic phenotype in the tumor. Among the many new endothelial growth factors, vascular endothelial growth factor (VEGF) is known to be particularly responsible for promoting the neovascularization in human breast cancer. METHODS: Intratumoral protein levels of VEGF were measured by enzymatic immunoassay in 135 primary breast cancer tissues. The VEGF levels were compared with the microvessel density evaluated by immunostaining the endothelial antigen and also were compared with intratumoral protein levels of other endothelial growth factors, including basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). RESULTS: Intratumoral VEGF concentrations varied from 3.3 pg/mg protein to 2032 pg/mg protein (average 148 pg/mg protein). An immunocytochemical analysis using anti-VEGF antibody confirmed that VEGF was located mainly in the cytoplasm of the tumor cells. The VEGF concentrations were significantly higher in vascularly rich tumors than in vascularly poor tumors. No significant association was found between VEGF concentrations and the two other endothelial growth factor concentrations. CONCLUSIONS: The quantitation of intratumoral VFGF levels seems to be useful for assessing the activity of tumor angiogenesis.

Breast Neoplasms↗
PubMed1996

The coexistence of systemic sclerosis and rheumatoid arthritis in five patients. Clinical and immunogenetic features suggest a distinct entity.

To elucidate the clinical characteristics and pathogenesis of scleroderma-rheumatoid arthritis (SSc-RA) overlap syndrome, we analyzed the clinical features of 5 patients with SSc-RA overlap. Their HLA phenotypes and genotypes were also determined. Generalized skin sclerosis, severe seropositive polyarthritis, pulmonary fibrosis, anti-topoisomerase I antibodies, and HLA-DR4,53;DQA1*0301;DBQ1*04 haplotype were observed in all of the patients. Similar clinical features were recognized in most of the 10 cases reported previously. Our case studies indicate that SSc-RA overlap may be a distinct entity.

Aged↗
PubMed1996

Chronological changes in the complement system in sepsis.

The time courses of serum complement levels and the severity of sepsis were compared in two groups of septic patients, one in which the patients survived (surviving group) and one in which they did not (nonsurviving group). The components of the complement system, namely, C3a, C4a, C5a, CH50, C3, C4, and C5, were measured at several points in time after the diagnosis of sepsis had been established. A 2-antibody radioimmunoassay was used to measure C3a, C4a, and C5a; the latex agglutination test was used to measure C3 and C4; nephelometry was used to measure C5; and Meyer's 50% hemolysis method was used to measure CH50. Following the diagnosis of sepsis, the levels of CH50, C3, and C4 were significantly lower in the nonsurviving than the surviving group, while the levels of C3a and C4a were significantly higher in the nonsurviving than the surviving group. The C5a levels were significantly higher in the nonsurviving than the surviving group, although no significant intergroup differences were subsequently noted. These results suggest that the serum levels of C3a, C4a, C5a, CH50, C3, and C4 could serve as indices of the severity of sepsis. Thus, monitoring the complement system may be useful for predicting the outcome of patients with sepsis.

Adult↗
PubMed1996

Adenocarcinoma in the anal canal associated with a fistula: report of a case.

Adenocarcinoma in the anal canal associated with an anal fistula is extremely rare, and in most cases its origin is difficult to ascertain because the primary sites have already been destroyed before any diagnosis of malignancy is able to be made. We report herein the case of a 62-year-old man found to have papillary adenocarcinoma with partial mucinous carcinoma associated with an anal fistula. The tumor was not exposed to the mucosal surface of the anal canal or rectum and an abdominoperineal resection was carried out. Macroscopic findings suggested that the tumor had developed from the anal fistula; however, the tumor showed a positive results when tested for O-acetylated sialic acids. This test also proved positive in the mucus of normal rectal mucosa, but not in the mucus of the anal glands. We speculated that the results of these tests may indicate that this tumor could have originated from the rectal mucosa, from where it migrated into the anal fistula.

Adenocarcinoma, Mucinous↗