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Biomedical subjects

K Nagayama

Publications and source records attributed to K Nagayama.

At least 73 records · Page 4Linked to original sources

Association of Ile462Val (Exon 7) polymorphism of cytochrome P450 IA1 with lung cancer in the Asian population: further evidence from a case-control study in Okinawa.

Okinawa, a group of islands that lie between the East China Sea and the Pacific Ocean, 2000 km south of the Japanese main islands, has a different profile of diseases, ethnicities, and cultures than does the rest of Japan. We examined an Ile462Val polymorphism (CYP1A1*2 allele) of cytochrome P450 IA1 in a hospital-based case-control study of lung cancer patients (247 cases and 185 controls) in Okinawa to ascertain the association of this variant with lung cancer. In addition, the distribution of this genotype was studied in populations from different areas of Japan, including Tokyo (n = 69) and Iwate (northern part of Japan; n = 81), as well as in a Chinese group from the Jiangsu province (n = 39) and in an Australian Caucasian group (n = 146). Genotype frequency in controls was not significantly different from area to area in Japan. In Okinawa, however, the genotype encoding Val/Val was associated with a significantly higher risk of lung cancer (odds ratio = 3.32, P = 0.013), especially of squamous cell carcinoma and small cell carcinoma (odds ratio = 4.85 and 9.35, respectively). The Val-encoding allele was less frequent in the Chinese population and was rare in Australian Caucasians. Thus, this study gives support to the value of the cytochrome P450 IA1 Ile462Val polymorphism as a practical high-risk marker of lung cancer in populations, especially those in southeast Asia, in which this variant is more common.

Adult↗

Bacterial invasion induces interleukin-7 receptor expression in colonic epithelial cell line, T84.

The intestinal epithelial layer forms the interface between the external and the internal environments of a host. Since the interleukin-7 (IL-7) and IL-7 receptor (IL-7R) signaling pathway has been shown to play an important role in the mucosal immune system, we studied the expression of IL-7R in T84, a colonic epithelial cell line, after cells were infected with several types of enteropathogenic bacteria, including Salmonella typhimurium, enteropathogenic Escherichia coli and enteroinvasive Escherichia coli. Bacterial invasion induced IL-7R expression in T84 assessed by a semi-quantitative reverse transcription-polymerase chain reaction technique and flow cytometry. The inhibition of bacterial invasion by cytochalasin D, a specific inhibitor of actin polymerization, led to a reduction in the expression of IL-7R. These data indicate that bacterial invasion into intestinal epithelial cells is likely to be an essential process in the induction of IL-7R. The communication between the epithelium and mucosal lymphocytes which is mediated via IL-7 and IL-7R may be involved in the modulation of the mucosal inflammation which occurs in bacterial infection.

Antigens, CD↗

Protein arrays: concepts and subjects.

To adapt proteins, the materials in life, for use as materials in science and technology, we focused not only on the biological aspects (functional aspects) but also on the material aspects as matter (structural and physical aspects). Engineering with protein arrays will develop under such consideration and advance toward stable devices made of protein molecules. The protein arrays with 2D crystalline order provide a primary model of macroscopic protein-based devices. The combination of protein engineering, the leading edge of life science, and array engineering, the leading edge of materials science, will provide clues to the controlled integration of protein molecules to a form of functional supramolecules on proper surfaces.

Adsorption↗

Assembly process of 2D protein arrays in wetting films.

We were successful in developing a technique to form protein array developed directly on solid surfaces. This promising array formation revealed two new concepts of the ordering mechanism: the lifetime of a secondary minimum and secondary films. These concepts are not limited to our film formation technique. Any electrolytic thin film on a solid surfaces or any free film may contain a secondary film. If the secondary film can be retained in an electrolytic thin film for a sufficient period, a large single domain of small colloidal particles, such as proteins, fine metal particles, fine semi-conductive particles, etc., can be produced by an Alder-type transition.

Air↗

Hepatic denervation ameliorates sodium and water retention in experimental cirrhosis in rats.

Increased activity in the hepatic sympathetic nervous system may exacerbate salt and water retention in patients with liver cirrhosis. The aim of this study was to evaluate sodium and water homeostasis in rats with cirrhosis induced by diethylnitrosamine and to investigate the influence of hepatic denervation in this model. Animals were randomized into three groups: diethylnitrosamine-treated rats with (N = 13) and without (N = 8) hepatic denervation and control rats (N = 8). Rats were fed a normal salt diet (0.23% sodium ad libitum). The 24-hr measurements for sodium balance, water balance, and creatinine clearance were performed every two weeks for 12 weeks after surgery. Diethylnitrosamine-induced cirrhosis was confirmed histologically. The cumulative change in sodium balance in the innervated diethylnitrosamine-treated rat increased progressively and was significantly higher than the control during the last four weeks of the study. Meanwhile, rats with hepatic denervation showed significantly smaller changes in cumulative sodium balance at week 12 than those in the innervated group. The cumulative changes in water balance in the innervated group were significantly greater at weeks 10 and 12 than those of the denervated and control group, which remained unchanged throughout the study. Creatinine clearance in the innervated group decreased at weeks 10 and 12 by approximately 70% from baseline (P < 0.05); in contrast, it did not change significantly in the denervated group and control group throughout the study. These results demonstrated that hepatic denervation ameliorates sodium and water retention as well as glomerular function in cirrhosis model in rats.

Animals↗

Invasive phenotype of Vibrio parahaemolyticus.

Many studies have been done on the virulence factors of Vibrio parahaemolyticus, which causes acute gastroenteritis. Invasion by this bacterium of culture cells in vitro, however, has not been clearly demonstrated. To assess the invasive ability of V. parahaemolyticus, quantitative studies using antibiotic survival assays were done. Of 21 isolates examined, 4 could invade Caco-2 cells, a human colon carcinoma-derived cell line. Invasion of an isolate, AQ4023, was inhibited by cytochalasin D, nocodazole, and genistein. This indicates that active processes in cells, such as signal transduction by tyrosine protein kinase, may be involved in the internalization of this bacterium by Caco-2 cells and that actin filaments and cytoskeletal structure may have important roles in this process. These results suggested that the disease caused by some isolates of V. parahaemolyticus is attributable not only to toxin production but also to invasion into intestinal epithelium.

Caco-2 Cells↗

Epidemiological study on infectious diarrheal diseases in children in a coastal rural area of Kenya.

Diarrheal diseases are major causes of morbidity and mortality among children in developing countries. We have analyzed the causative agents of diarrhea in children under five years of age who resided in rural environments but attended a hospital in Malindi, a coastal town in Kenya. Bacterial diarrhea was found in 239 (27.7%) of 862 patients with diarrhea. Diarrheagenic Escherichia coli, including enteropathogenic, enterotoxigenic, and enterohaemorrhagic strains, was isolated from 119 (13.8%) patients, followed by Salmonella spp. (63 cases, 7.3%) and Shigella spp. (56 cases, 6.5%). Intestinal parasites were found in 109 (12.6%) of the patients. Entamoeba histolytica and Giardia lamblia were found in 67 (7.8%) and 42 (4.9%) of the cases, respectively. Rotavirus was found in 69 (16.1%) of 428 cases, a part of the 862 cases. Significant differences in age distribution were seen in diarrheal cases due to Campylobacter spp., G. lamblia, and rotavirus. No significant seasonal incidence of specific pathogens was found, but the number of diarrheal patients was significantly correlated to rainfall. Drinking water was contaminated with bacteria at concentrations ranging from 10(3) to 10(6) CFU/ml in 98% of the households and by coliform bacteria at concentrations of 10(2) to 10(5) CFU/ml in 72% of the households. These results suggest that the main routes of infection may be contaminated drinking water and fecal-oral transmission of enteric pathogens. Consequently, we propose that the enhancement of hygienic practice through health education is a feasible control measure of diarrhea in the study area.

Age Distribution↗

Hemolysis, elevated liver enzymes, and low platelets syndrome associated with primary anti-phospholipid antibody syndrome.

A 28-year-old woman with a history of a spontaneous abortion developed thrombocytopenia, Coombs-negative hemolytic anemia, and liver dysfunction at the sixteenth week of pregnancy. These findings were compatible with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome (hemolysis, elevated liver enzymes, and low platelet counts). Moreover, serum anti-phospholipid antibodies were positive, suggesting the association of anti-phospholipid antibody syndrome. An artificial abortion, anti-coagulation therapy, and plasma exchange were performed concomitantly with corticosteroid therapy. She responded to the therapy, a remission was obtained. Anti-phospholipid antibodies may play a role in the pathogenesis of HELLP syndrome.

Abortion, Induced↗

[A novel marker of development of HUS associated with enterohemorrhagic Escherichia coli infection--thrombomodulin levels in the blood].

Vero toxins-mediated vascular endothelial cell damage is thought to play a central and important role in the pathogenesis of HUS associated with EHEC infection. Thrombomodulin (TM) is an endothelial membrane protein inhibiting procoagulant activities of thrombin. Elevation of soluble TM in the blood is regarded a possible marker for endothelial cell damage. To test whether serum TM acts as an indicator for HUS, we evaluated serum TM in 21 children with HUS, 31 children with hemorrhagic colitis(HC), and 25 healthy age-matched controls. TM levels in acute HUS patients (6.89 +/- 1.91 ng/ml) were significantly higher when compared with in acute HC patients(3.15 +/- 0.37 ng/ml) and in the controls (2.77 +/- 0.42 ng/ml) (p < 0.001, respectively). This result indicated that serum TM may be an useful marker for the development of HUS.

Acute Disease↗

[Considerations on the fundamental structure and characteristics of the "Amae" phenomenon--clarification of the "Amae-theory (Takeo Doi)"].

It is well-known that Takeo Doi tried to describe Japanese culture using the Japanese term "Amae". However, with many Japanese students of psychotherapy pointing out that his use of the term was arbitrary, his Amae-theory fell into confusion. Actually, with the single word Amae, he explained many heterogeneous psychological phenomena including pathological dependency as well as maternal separation. In this paper, I use my own clinical observations to clarify the Amae-phenomenon and define it as follows: The "Aame" the Japanese usually experience in daily life differs from both pathological dependency (which M. Balint described as "ocnophilia"), and an affinity for friendly expanses in the therapeutic depressive position (described by M. Balint as "philobatism", by me as "sumu-akirameru"; c.f. Keiichi Nagayama: Considerations on the Guilt Feeling towards Mother and Maternal Separation using the Japanese Keywords "Sumu-Akirameru" and "Sumanai", Psychiatria et Neurologica Japonica, 96: 83-108, 1994). In psychotherapy, Japanese patients only become able to form Amae connections with others after experiencing the two opposites (ocnophilia and philobatism) mentioned above. Although Amae is phenomenologically different from those extremes, it consists of two elements carrying some attributes from those extremes. One element consists of interpenetrating and mutually interdependent personal relations in a small familiar group; and the other element is a kind of protective and harmonious space in which the Japanese enjoy "temporary and partial regression in the service of the ego". As these two elements are both present in Amae, where dependence and independence are concerned, Amae toes the midline and has a double meaning. A fundamental principle of interpersonal relationships in Japanese society, Amae calls upon members of a small group to be moderately individualistic. If a member lacks ego flexibility regarding Amae and cannot obey this principle, he cannot adapt to a small familiar group. From the Western standpoint of individuality, Amae and interpenetrating personal relations in Japanese society must be regarded as regressive phenomena, whereas, for the Japanese, Amae is a personal skill necessary for social adaptation. Whereas Sumu-Akirameru (Nagayama) and Philobatism (Balint) are ontological phenomena that tend to avoid external objects, Amae involves the need for relationships and is a somewhat socialized phenomenon in Japan. Although Amae and Sumu-Akirameru are different phenomena, they share several characteristics: 1) both tend towards protective harmonious spaces which have both specialty and boundaries; 2) things arise spontaneously and unintentionally in both phenomena; 3) the Japanese use both to confirm their sense of self; 4) both have the qualities of "corporality" and "living in". Because of these common areas, the Japanese tend to perceive Sumu-Akirameru and Amae as one experience, although they are different, separate phenomena. This tendency leads the Japanese to group behavior patterns, and unconsciously forces them into a double bind between individualization and group behavior patterns. This cultural tendency and phenomenological ambiguity of Amae itself allow the Japanese to easily project many kinds of psychological phenomena onto Amae. It is this projection deeply rooted in Japanese culture that confused the Amae-theory (Doi). Clarification of this cultural tendency not only contributes to the study of Japanese psychotherapy (Morita therapy, Naikan therapy), but also to that of "narcissism" and Preoedipal subjects in psychoanalysis.

Adult↗

[New combination therapy with FTM [5-FU, pirarubicin (THP) and MMC] for treatment of inoperable advanced gastric cancer].

Clinical usefulness of a new combination FTM therapy consisting of 5-FU, Pirarubicin (THP) and MMC for the treatment of advanced gastric cancers was investigated. 5-FU, THP or MMC was administered at a dose of 600 mg/m2 on day 1, 8, 22 and 29, 30 mg/m2 on days 1 and 22, and 10 mg/m2 on day one only of each course, respectively. Eighteen patients with inoperable advanced gastric cancer were treated with FTM. All drugs were investigated by intravenously by one shot. The tumor response rate was 50% [9 of 18 showed PR]. The survival rate was higher in responders than in nonresponders (18.1% vs 11.1%) (p < 0.05). Side effects in the gastrointestinal tract were minimal. Cardiotoxicity and nephrotoxicity were not detected, but myelosuppression was prominent in most cases. G-CSF was given in sixteen patients (88%), and platelet transfusion was performed in two patients (11%). New combination FTM therapy is an effective treatment regimen even for advanced inoperable gastric cancer.

Adult↗

Wheat germ agglutinin-reactive chains of giant hemoglobin from the polychaete Perinereis aibuhitensis.

Wheat germ agglutinin-reactive chains of multisubunit extracellular hemoglobin from the polychaete Perinereis aibuhitensis were identified to clarify the carbohydrate gluing which is the carbohydrate-dependent supramolecular architecture of the hemoglobin (Ebina S. et al. (1995) Proc. Natl. Acad. Sci. USA 92, 7367-7371). Electron microscope micrographs of Perinereis hemoglobin showed a characteristic shape of two-tiered hexagonal rings whose diameter and height were determined to be 29.4 +/- 1.7 nm and 20.0 +/- 1.8 nm, respectively. Four types of globins and two types of linkers were isolated from the giant hemoglobin by reverse-phase chromatography and SDS-PAGE. These constituents showed similar NH2-terminal sequences as those previously reported for corresponding chains of Tylorrhynchus hemoglobin (Suzuki T. and Gotoh T. (1986) J. Biol. Chem. 261, 9257-9267; Suzuki T. et al. (1990) J. Biol. Chem. 265, 12168-12177). Thus, each globin of Perinereis hemoglobin was identified in terms of amino acid sequence homology and designated using names common to Tylorrhynchus hemoglobin, namely, a, A, b, and B. The linkers were stained by horseradish peroxidase (HRP)-lectins and PAS staining kits, indicating the presence of carbohydrate oligomers. Lectin staining was also significantly positive to globins a and A, which belong to strain A, but negative to globins b and B, which belong to strain B. Results showed that linkers and globins of strain A had a site in a carbohydrate oligomer to which wheat germ agglutinin (WGA) could bind. On the other hand, an alignment between known amino acid sequences of annelid globins and linkers and the sequences of lectins revealed that only the domain of the cysteine-rich motif in linkers has a homology with WGA-type lectins. The results of this study clarify the structuring mechanism of a supramolecule by lectin-like binding, called carbohydrate gluing.

Amino Acid Sequence↗