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Biomedical subjects

K Taniguchi

Publications and source records attributed to K Taniguchi.

At least 145 records · Page 8Linked to original sources

Induction of the p16INK4a senescence gene as a new therapeutic strategy for the treatment of rheumatoid arthritis.

Synovial tissue affected by rheumatoid arthritis is characterized by proliferation, which leads to irreversible cartilage and bone destruction. Current and experimental treatments have been aimed mainly at correcting the underlying immune abnormalities, but these treatments often prove ineffective in preventing the invasive destruction. We studied the expression of cyclin-dependent kinase inhibitors in rheumatoid synovial cells as a means of suppressing synovial cell proliferation. Synovial cells derived from hypertrophic synovial tissue readily expressed p16INK4a when they were growth-inhibited. This was not seen in other fibroblasts, including those derived from normal and osteoarthritis-affected synovial tissues. In vivo adenoviral gene therapy with the p16INK4a gene efficiently inhibited the pathology in an animal model of rheumatoid arthritis. Thus, the induction of p16INK4a may provide a new approach to the effective treatment of rheumatoid arthritis.

Adenoviridae↗

Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: a novel drug carrier for cancer targeting therapy.

The tissue distribution of anti-tumour vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles from isolated rat tumour-derived endothelial cells (TECs) was assessed in various tumour-bearing animals. Radiolabelled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, the source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumour tissue in nude mice, radioactivities of 125I-labelled TES-23 were also up to 50 times higher than those of control antibody with little distribution to normal tissues. The selective recognition of TES-23 to TECs was competitively blocked by preadministration of unlabelled TES-23 in vivo. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in oesophagus cancers. These results indicate that tumour vascular endothelial cells express common antigen in different tumour types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, was tested for its anti-tumour effect in rats bearing KMT-17 fibrosarcomas. The immunoconjugate (TES-23-NCS) caused marked regression of the tumour, accompanied by haemorrhagic necrosis. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumour vascular endothelium and its application to many types of cancer.

Adenocarcinoma↗

Systemic immune response after intravesical instillation of bacille Calmette-Guérin (BCG) for superficial bladder cancer.

The mechanism of anti-tumour activity by BCG is not known clearly. However, many studies suggest that immunological response is related to effectiveness of intravesical instillation of BCG in the therapy for superficial bladder carcinoma. Peripheral blood mononuclear cells (PBMC), urine and serum were obtained from patients with superficial carcinoma at various times during the course of BCG instillation. Urine of patients showed increased levels of IL-1beta, IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and macrophage colony-stimulating factor (M-CSF) after BCG instillation. Levels of IL-2 and IFN-gamma in the serum also increased after BCG instillation, but IL-1beta, IL-6, TNF-alpha and M-CSF were not detectable. Maximal levels of IL-2 and IFN-gamma in the urine or serum were shown after the fourth instillation. BCG-induced killer cell activity in PBMC increased significantly after the third BCG instillation. These results suggest that BCG instillation involved not only local immunological efforts but also systemic immune responses. Tumour-free patients produced higher BCG-induced killer cell activity than tumour recurrence patients. BCG-induced killer cell activity may be useful for monitoring the effectiveness of intravesical BCG instillation.

Administration, Intravesical↗

Immunological background in children with persistent diarrhea in Ghana.

BACKGROUND: Persistent diarrheal diseases have become one of the most serious medical problems in developing countries, but few studies have been conducted to determine the risk factors. In the present study, we investigated the nutritional and immunological background in children with persistent diarrhea in comparison with those with acute diarrhea. METHODS: Children with diarrhea who were brought to the Oral Rehydration Salt Clinic of Princess Marie Louise Children's Hospital in Accra were evaluated from an immunological and nutritional aspect. In the follow-up visit, the cases whose diarrhea stopped within 2 weeks after onset were classified into the acute diarrhea group; those with diarrhea lasting more than 2 weeks were classed in the persistent group. Nutritional and immunological data at the initial visit were compared between these two groups. RESULTS: In general, the diarrhea cases had a tendency to undernutrition and impaired cellular immunity compared with healthy control. Persistent cases had lower values for longer half-life, rapid turn-over proteins. Persistent cases had a higher percentage of CD8+ cells and lower CD4/CD8 ratio. CD25 expression in CD4+ cells stimulated by anti-CD3 antibody was lower in the persistent diarrhea group. CONCLUSION: These results appear to support the hypothesis that more severe nutritional status and impairment of cellular immunity is related to the persistence of diarrhea.

CD4-CD8 Ratio↗

Infantile fibrosarcoma. Report of two cases.

We present two cases of infantile fibrosarcoma, one of which was thought to be a congenital tumour on the thigh and was initially diagnosed as a haemangioma, and the other was a tumour on the trunk. Although both recurred locally after initial surgical treatment, wide local re-excision controlled the disease without adjuvant treatment.

Female↗

Heterogeneous expression of glycoconjugates among individual glomeruli of the hamster main olfactory bulb.

Glomeruli within the main olfactory bulb (MOB) are known as areas of synapse formation between axon terminals of olfactory neurons in the olfactory epithelium and dendrites of the first relay neurons (mitral and tufted cells) in the MOB, so that they serve as functional units in olfaction. We examined expression patterns of glycoconjugates in the glomeruli of the hamster MOB by lectin histochemistry using 21 biotinylated lectins. Thirteen lectins, WGA, s-WGA, DSL, DBA, SBA, WA, SJA, RCA-I, PNA, ECL, UEA-I, PSA and LCA, showed differential binding patterns among the glomeruli. To evaluate these differential binding patterns of lectins, we analysed staining intensity of each of the 13 lectins on the level of individual glomeruli by image analysis, and classified staining intensity into five grades (negative, 1+, 2+, 3+, 4+) on the basis of results obtained. This classification enables us to make detailed comparison among individual glomeruli. We further analysed the grade of staining intensity of each of the 13 lectins in the same glomerulus in adjacent serial sections by image analysis, and found that individual glomeruli varied in combination of grades of staining intensity and kinds of lectins. These results indicate that glycoconjugates are expressed heterogeneously in individual glomeruli, and that heterogeneous expression may contribute to the topographic organization of the primary olfactory pathway.

Animals↗

Direct evidence for in vivo reversible tyrosine phosphorylation of the N-terminal domain of the H/K-ATPase alpha-subunit in mammalian stomach cells.

In vivo reversible phosphorylation of Tyr-7 and Tyr-10 of the pig stomach H/K-ATPase alpha-chain was initially demonstrated in mammals, rat, rabbit, and pig, in the presence of vanadate + H(2)O(2). In vitro phosphorylation has also been unequivocally demonstrated via the use of protease inhibitors during membrane H/K-ATPase preparation. An amphoretic detergent permitted each intrinsic kinase to phosphorylate each fusion protein containing the requisite Tyr residues, along with a reduction in alpha-chain phosphorylation. These and other data suggest that some important enzyme systems are present in the apical membrane and that they are in sufficient proximity to participate in the reversible phosphorylation of the amino terminal soluble domain of the alpha-chain with an unknown physiological function in the membrane embedded H/K-ATPase.

Animals↗

Sequence analysis of VP1 and VP7 genes suggests occurrence of a reassortant of G2 rotavirus responsible for an epidemic of gastroenteritis.

G2 rotavirus was prevalent in a 1993 epidemic of acute gastroenteritis in Taiwan. In this study, the genetic relationship among G2 rotavirus strains was analysed. The VP7 genes were amplified and sequenced. Except for one strain isolated in 1981, the nucleotide sequences of the VP7 genes of most of the G2 rotaviruses were very similar (identity > 97%) and were closely related to that of a Japanese G2 reference strain, S2. The genetic relatedness of G2 rotaviruses was analysed further by RNA-RNA hybridization. The genomes of the major G2 strains of 1993 did not hybridize well with those of the G2 strains of previous seasons in RNA segments 1, 6 and 7. Partial nucleotide sequences of the VP1 gene were analysed and appeared to be similar among the major G2 strains from the same epidemic (identity > 98%), whereas the identity of the VP1 genes of the major G2 strains of the 1993 epidemic to those of previous seasons was only about 84%. Since the numbers of mutations accumulated in the VP1 and VP7 genes over a period of 10 years were comparable, the significant change in the VP1 genes of the major strains of the 1993 epidemic suggests that these G2 rotaviruses had evolved by genetic reassortment.

Amino Acid Sequence↗

Left posteroseptal Mahaim fiber associated with marked longitudinal dissociation.

We report a patient who underwent radiofrequency catheter ablation of a left posteroseptal atrioventricular (AV) Mahaim fiber with a marked longitudinal dissociation. During atrial pacing, Wenckebach-type atrioventricular block over the accessory pathway was observed with progressive preexcitation and no change in polarity of the delta waves. The AV conduction curve was discontinuous, with a distinct "jump-up" in local AV conduction time of 84 ms. The earliest ventricular activation was recorded from the posteroseptal portion of the mitral annulus, and the unipolar electrogram from a distal electrode had a high, steep deflection with uniphasic QS-like activity with 62 ms of local AV conduction time.

Adult↗

The effect of mechanical trauma on the tooth germ of rat molars at various developmental stages: a histopathological study.

Intrusive trauma was experimentally applied to the tooth germ at different developmental stages in the rat first molar. The tooth germ at the earliest (postnatal day 1, initiating stage of enamel matrix formation) and the latest (postnatal day 10, calcifying stage of preformed enamel matrix) developmental stages studied showed localized enamel hypoplasia as a direct sequela of trauma. The tooth germs in which enamel matrix was rapidly thickening (postnatal days 3, 5, 7) and had not yet started to calcify showed the most intense and extensive injuries to the formation and structural organization of both enamel and dentin. As for indirect effects secondary to trauma, tooth germ dislocation was observed chiefly in tooth germs at the same developmental stages, frequently resulting in ankylosis. The present experimental model may be helpful for clarifying the histogenesis of traumatic changes in the developing tooth germ.

Ameloblasts↗

[Current status of Japanese encephalitis in Japan].

Japanese encephalitis (JE) cases confirmed by serological and/or virological tests, and clinically typical fatal JE cases have been collected using individual report cards in Japan since 1965. A total of 324 confirmed cases (male: 167, female: 157) reported between 1982 and 1996 were analyzed. Annual incidence of JE cases was less than one hundred cases from 1982 to 1991, and less than 10 cases after 1992. Age distribution of the patients was: 0-9 years old, 43 cases (13%); 10-39 years old, 30 cases (9%); 40-69 years old, 161 cases (50%); over 70 years old, 90 cases (29%). The highest incidence in male cases was observed in the age group of 50-59 years, and that in female was in 60-69 years. Most of the patients (95%) were living in the western parts of Japan. No patient was reported from Okinawa, southern-most prefecture of Japan, and from Tohoku-Hokkaido area, northern parts of Japan. The date of onset were distributed from the end of July to the end of October, and the highest incidence was observed in the end of August. Prognosis of the patients were: complete recovery, 99 cases (31%); sequelae, 156 cases (48%); total, 56 cases (17%); unknown, 13 cases (4%). Vaccination histories of patients were reported as vaccinee, 4 cases (1%); incomplete vaccinee, 14 cases (4%); non-vaccinee, 181 cases (56%); unknown, 125 cases (39%). Spread of JE virus in Japan has not been diminished as shown by the data of antibody acquisition of young swine in every summer in Japan. Based on these observations we conclude that JE vaccination has contributed to maintaining the low JE incidence among children in Japan.

Adolescent↗

Identification of functional amino acids in the macrolide 2'-phosphotransferase II.

Macrolide 2'-phosphotransferase [MPH(2')] transfers the gamma phosphate of ATP to the 2'-OH group of macrolide antibiotics. The role of aspartic acids in the putative ATP-binding site of MPH(2')II was investigated through the substitution of alanine for aspartate by site-directed mutagenesis. D200A, D209A, D219A, and D231A mutant strains were unable to inactivate the substrate oleandomycin, while a D227A mutant retained 7% of the activity of the original enzyme.

Adenosine Triphosphate↗

Evolution and biological characterization of human immunodeficiency virus type 1 subtype E gp120 V3 sequences following horizontal and vertical virus transmission in a single family.

It has been suggested that immune-pressure-mediated positive selection operates to maintain the antigenic polymorphism on the third variable (V3) loop of the gp120 of human immunodeficiency virus type 1 (HIV-1). Here we present evidence, on the basis of sequencing 147 independently cloned env C2/V3 segments from a single family (father, mother, and their child), that the intensity of positive selection is related to the V3 lineage. Phylogenetic analysis and amino acid comparison of env C2/V3 and gag p17/24 regions indicated that a single HIV-1 subtype E source had infected the family. The analyses of unique env C2/V3 clones revealed that two V3 lineage groups had evolved in the parents. Group 1 was maintained with low variation in all three family members regardless of the clinical state or the length of infection, whereas group 2 was only present in symptomatic individuals and was more positively charged and diverse than group 1. Only virus isolates carrying the group 2 V3 sequences infected and induced syncytia in MT2 cells, a transformed CD4(+)-T-cell line. A statistically significant excess of nonsynonymous substitutions versus synonymous substitutions was demonstrated only for the group 2 V3 region. The data suggest that HIV-1 variants, possessing the more homogeneous group 1 V3 element and exhibiting the non-syncytium-inducing phenotype, persist in infected individuals independent of clinical status and appear to be more resistant to positive selection pressure.

Amino Acid Sequence↗

Quantitative analysis of surface P-wave morphology in isthmus ablation for type 1 atrial flutter: differentiation between complete isthmus block and slow isthmus conduction.

Changes in P-wave morphology in inferior leads during atrial pacing at the margins of the carvo-tricuspid isthmus have been reported to be useful for predicting the creation of isthmus block in radiofrequency (RF) ablation of type I atrial flutter (AFL). However, it is not known whether these changes in P-wave morphology allow the clinician to differentiate between complete isthmus block and slow isthmus conduction. P-wave morphology during low lateral right atrial (LLRA) pacing, as well as during coronary sinus ostium (PCS) pacing, was evaluated prior to ablation, during slow isthmus conduction, and after complete isthmus block in 30 patients with AFL. Changes in P-wave morphology during LLRA pacing were not sufficient to differentiate between complete isthmus block and slow isthmus conduction. While changes in P-wave morphology in lead II from inverted to biphasic during PCS pacing were observed in both slow isthmus conduction and complete isthmus block, the ratio of the positive component to the total P-wave amplitude (P-wave ratio) was significantly different between slow isthmus conduction (20+/-17%) and complete isthmus block (40+/-11%) (P<0.0001). When the P-wave ratio in lead II during PCS pacing was more than 75% of the F-wave ratio in lead II during AFL, bilateral complete isthmus block was predicted with a sensitivity of 88%, a specificity of 71%, a positive predictive value of 75%, and a negative predictive value of 85%. These results indicate that a P-wave ratio greater than 20% or a P-wave ratio during PCS pacing greater than 75% of the F-wave ratio during AFL may predict a bidirectional complete isthmus block.

Aged↗

The time from anaerobic threshold (AT) to respiratory compensation point reflects the rate of aerobic and anaerobic metabolism after the AT in chronic heart failure patients.

The significance of the time from anaerobic threshold to respiratory compensation point (RCP-AT time) in patients with chronic heart failure was investigated. Thirty-seven patients with chronic heart failure (New York Heart Association class II or III) were enrolled into the study. Cardiopulmonary exercise testing was performed using breath-by-breath gas sampling. A bicycle ergometer was used, and incremental exercise testing was carried out. Anaerobic threshold, respiratory compensation point (RCP), and the slope of oxygen uptake (VO2) as a function of work rate (deltaVO2/deltaWR) were measured. A positive correlation (r=0.53) between RCP-AT time and deltaVO2/deltaWR was found. RCP-AT time was corrected for the whole exercise period (ramp exercise-RCP point), and the correlation between corrected RCP-AT time and deltaVO2/deltaWR was still present (r=0.46). There was no correlation between RCP-AT time and anaerobic threshold. These findings suggest that RCP-AT time is a new parameter that reflects the rate of the aerobic and anaerobic metabolism after AT.

Anaerobic Threshold↗