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Biomedical subjects

H Kasuga

Publications and source records attributed to H Kasuga.

At least 19 recordsLinked to original sources
PubMed2001

Effects of anti-TGF-beta type II receptor antibody on experimental glomerulonephritis.

BACKGROUND: Renal fibrosis, characterized by the accumulation of extracellular matrix (ECM), is a common histopathological feature of progressive renal disease of diverse etiology. Interaction between transforming growth factor-beta (TGF-beta) and TGF-beta type II receptor (TGF-betaIIR) may play an important role in the ongoing fibrotic process. TGF-betaIIR and TGF-beta have been reported to be up-regulated in human glomerulopathies. In order to block the TGF-beta system, many studies have inhibited TGF-beta itself, but not its receptors. Our study explored the effects of fully human monoclonal antibody against TGF-betaIIR (hTGF-betaIIRAb) on experimental proliferative glomerulonephritis. METHODS: hTGF-betaIIRAb was generated from Xenomice. The expression of TGF-betaIIR was studied by immunohistochemistry in normal and anti-Thy-1 nephritis rats. hTGF-betaIIRAb or control Ab was injected intraperitoneally at day 0 and day 4 of anti-Thy-1 nephritis, and rats were sacrificed at day 7. Effects of hTGF-betaIIRAb were assessed by histological and immunopathological measurements. RESULTS: The specificity of hTGF-betaIIRAb was confirmed by ELISA and Western blot analysis. By immunostaining, TGF-betaIIR expression was up-regulated in the proliferative lesions of anti-Thy-1 nephritis at day 7. In the hTGF-betaIIRAb-treated group, the extent of mesangial expansion was less than that in the control group. By immunohistology, alpha-smooth muscle actin, fibronectin-EDA, and type I collagen were significantly reduced in the hTGF-betaIIRAb-treated group. CONCLUSIONS: Anti-TGF-betaIIR antibody ameliorated ECM accumulation in anti-Thy-1 nephritis. Our data suggest that TGF-betaIIR may be one of the therapeutic targets, and that fully human monoclonal antibody against TGF-betaIIR may have a new therapeutic potential for renal fibrosis.

Actins↗
PubMed2001

Pathogenicity of Leucocytozoon caulleryi for specific pathogen-free laying hens.

The pathogenicity of Leucocytozoon caulleryi against specific-pathogen-free laying hens was investigated. Many large schizonts (second-generation schizonts) of L. caulleryi were seen in the ovary and oviducts of chickens. Edema and pressure atrophy of the adjacent tissues were associated with these schizonts. The eggshell-secreting portion of the uterus exhibited the most severe damage in the oviduct. This experiment reconfirms that L. caulleryi may stop egg production in laying hens, presumably as a result of damage to ovaries and oviducts.

Animals↗
PubMed1999

A clinicopathological study of lung cancer patients with occupational exposure to chrysotile asbestos fibers.

OBJECTIVE: To summarize the features of asbestos-related lung cancer. PATIENTS: Thirty-one lung cancer patients with occupational exposure to chrysotile asbestos fibers. They worked or had worked in one asbestos factory or its subcontracters. RESULT: All patients were male with mean age of 60.6 when diagnosed, and all except one were current or ex-'heavy' smokers. Histological types were fairly evenly divided into adeno-, squamous and small cell carcinoma and 24 (78%) of patients showed 'peripheral type' lung cancers. Regarding clinical stages, 20 patients (65%) were classified as III or IV (advanced stage). Tumor shadow(s) was detected on chest X-ray in 22 patients (71%), and in 5 patients with 'negative' chest X-ray, chest CT was necessary to recognize a primary tumor. Seventeen patients (55%) did not undergo periodical check-ups. CONCLUSION: Occupational asbestos exposure is interpreted as one of the important risks for lung cancer and frequent and accurate observation is necessary.

Adult↗
PubMed1999

Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin.

Excess of body fat, or obesity, is a major health problem and confers a higher risk of cardiovascular and metabolic disorders such as diabetes, hypertension, and coronary heart disease. Leptin is an adipocyte-derived satiety factor that plays an important role in the regulation of energy homeostasis, and its synthesis and secretion are markedly increased in obese subjects. To explore the metabolic consequences of an increased amount of leptin on a long-term basis in vivo, we generated transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. Overexpression of leptin in the liver has resulted in complete disappearance of white and brown adipose tissue for a long period of time in mice. Transgenic skinny mice exhibit increased glucose metabolism accompanied by the activation of insulin signaling in the skeletal muscle and liver. They also show small-sized livers with a marked decrease in glycogen and lipid storage. The phenotypes are in striking contrast to those of recently reported animal models of lipoatrophic diabetes and patients with lipoatrophic diabetes with reduced amount of leptin. The present study provides evidence that leptin is an adipocyte-derived antidiabetic hormone in vivo and suggests its pathophysiologic and therapeutic implications in diabetes.

Animals↗
PubMed1998

Tissue and cell type specificity of the human neurotrophin-3 promoter region in transgenic mice.

To examine the tissue and cell type specificity of the human neurotrophin-3 (NT-3) promoter, we generated transgenic mice bearing the 3.3 kbp upstream region of the human NT-3 gene linked to the bacterial chloramphenicol acetyltransferase (CAT) gene as a reporter. Eight independent founders of transgenic mice were obtained, and four of them transmitted the transgene to their offsprings. Among three lines of four transgenic mice at 6 weeks of age, a high level of production of CAT protein was detected in the spleen and a low level in the brain. By in situ hybridization analysis, CAT gene expression was detected in the hippocampal neurons and in the cerebellar granular neurons of the transgenic mouse brain. These results suggest that the 3.3 kbp 5' flanking region of the human NT-3 gene has adequate promoter activity in vivo and that its expression pattern resembles the endogenous gene.

Animals↗
PubMed1998

Per capita gross national product and summarized odds ratio for epidemiologic studies on the relationship between passive smoking and lung cancer.

The summarized odds ratios of epidemiologic studies on the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer by country were recalculated, using the odds ratio values in a 1992 report entitled, "Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders" by the US Environmental Protection Agency. The relationship between the summarized odds ratio and per capita gross national product (GNP) in 1964 was studied by the country. The graphic relationship between the summarized odds ratio (ordinate) and GNP (abscissa) showed an upward convex curve. The summarized odds ratios of a developing country (China) and developed countries (USA, Western Europe) in 1964 indicated a very weak association, while those of other countries (Greece, Hong Kong, and Japan) were slightly greater than unity (1.0). This means that ETS in the developing and developed countries in 1964 hardly affected lung cancer, whereas that in the other areas affected lung cancer somewhat. Socioeconomic status in developed countries is far better than that in developing countries, and factors related to socioeconomic status may affect the summarized odds ratio. It is recognized that cancer is diagnosed clinically some years after cancer risk factors appear. If the socioeconomic status involves some risk factors which affect lung cancer, the relationship between the summarized odds ratio and the GNP may be significant. Therefore, we can forecast that the summarized odds ratio of Japan will decrease to close to unity and that that of China will increase in the future because of economic growth, making it possible for the Chinese Government to adopt a policy to reduce the influence of ETS on health.

Air Pollutants↗
PubMed1997

[Autopsy findings of retroperitoneal cystic tumor and peliosis hepatis in lymphangiomyomatosis].

A 40-year-old woman who worked as a nurse and had suffered from progressive exertional dyspnea for about 14 years underwent open lung biopsy with surgical treatment for pneumothorax. The diagnosis was lymphangiomyomatosis and she was treated with danazol to suppress ovarian function. Her condition improved temporarily, but she died of respiratory failure when she was 47 years old. The survival time after the onset of respiratory symptoms was 21 years, and after the biopsy it was 8 years. At autopsy a retroperitoneal cystic tumor was found (9 x 7 x 5 cm), which had been evident clinically. Histologic examination showed that the tumor was an extrapulmonary manifestation of the lumphangiomyomatosis lesion. Some paraaortic lymph nodes has similar lesions. Aggregates of small red spots were seen on acute surface of the liver. These were diagnosed as peliosis hepatis, they may have been caused by the danazol.

Danazol↗
PubMed1997

[A study on the prognosis of patients with asbestos pleurisy].

We investigated the outcome of patients with asbestos pleurisy. The mean follow-up period of 12 patients was 6.5 +/- 3.7 years. Recurrence occurred in 5 patients (41.7%). Six of the cases recurred contralateral to the original lesion, while one recurred ipsilaterally. The mean period from onset to recurrence was 2.8 +/- 2.8 years. Five of the cases ended in death, and the mean period from onset to death was 5.0 +/- 3.1 years. Two patients died from pneumonia, 2 died from respiratory failure due to progressive pleural fibrosis, and 1 died from lung cancer. One of the 2 patients with progressive pleural fibrosis had leukopenia. It has been reported that the majority of cases of asbestos pleurisy resolve spontaneously, with a good prognosis. However, because of the possible mortality associated with respiratory failure caused by progressive pleural fibrosis, it seems prudent to follow patients with asbestos pleurisy closely.

Aged↗
PubMed1996

[Study on correlation between chest X-P course findings and change in antinuclear antibody in asbestos plant employees].

In order to investigate the correlation between a course of chest radiograms and changes in antinuclear antibody (ANA), 140 asbestos workers who had a chest radiogram and measurement of ANA in 1987 and had been working in the same plant were given the same examination again in 1992. In the group who showed a change in ANA to positive, the progression of pulmonary asbestosis was significantly higher than in the group who remained negative. Progression in pleural lesions was not significantly correlated.

Antibodies, Antinuclear↗
PubMed1994

Purification and partial amino acid sequence of initiatorin, a prostatic endopeptidase of the silkworm, Bombyx mori.

We have purified initiatorin, a prostatic endopeptidase that initiates the protein-arginine degradation cascade in the spermatophore of Bombyx mori. Purification of the enzyme from spermatophores was monitored by measuring BAEE (N alpha-benzoyl-L-arginine-ethyl ester) hydrolyzing activity. Spermatophores were used as a source for this enzyme. Of several isoforms the major form (MW, 29 kDa) was purified over 200-fold. The N-terminal sequence of initiatorin showed strong homology with those of serine-type of endopeptidases.

Amino Acid Sequence↗
PubMed1994

Production and properties of mouse monoclonal anti-adriamycin antibody.

Eight mouse IgG1 monoclonal anti-Adriamycin antibodies were produced in culture and in ascites in BALB/c nude mice. The binding constant and specificity was measured by an inhibition ELISA method. The assay was an indirect method using horseradish peroxidase-labeled goat Fab' antibody and 2mM ABTS (2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) containing 2.5 mM H2O2 as a color reaction reagent. The binding constant of the antibodies was 10(6) to 10(8) M-1. The antibodies possessed different specificities and affinities to the adriamycin. Though adriamycin is a low molecular weight (M.W. 579.99) hapten antigen, it possesses several epitopes as antigenic determinant sites. The antigenic epitopes of the adriamycin, which until recently were unknown, were analyzed by the monoclonal antibodies.

Animals↗
PubMed1994

Publication probability of a study on odds ratio value circumstantial evidence for publication bias in medical study areas.

A summarized odds ratio, calculated from odds ratios of published studies in a meta-analysis, may be overestimated because of publication bias. A method has been developed estimating indirectly the summarized odds ratio of all studies in a given research area, including not only those published but also unpublished. In the present study, a publication probability according to odds ratio value was obtained from the probability density function of all the studies, and a histogram of those published. A publication probability, according to odds ratio value, enables us to infer the quantitative relationship between publication probability and odds ratio. A notable nonpublication of studies whose odds ratios were close to unity was shown from examples of studies on the relationship between passive smoking and lung cancer, whereas nonpublication of studies whose summarized odds ratio was located far from unity was not detected from examples of studies on the relationship between cryptorchidism and testicular cancer. In both study areas, however, the differences between the summarized odds ratios, either with or without the hypothetical unpublished studies, were not large. The small difference, however, should not be ignored, when the study area is recognized as a social problem.

Cryptorchidism↗
PubMed1993

Heterogeneity in the molecular species of heat-stable enterotoxin of Vibrio cholerae non-O1 expressed by Escherichia coli carrying the cloned toxin gene.

The biological activity of the heat-stable enterotoxin of Vibrio cholerae non-O1 (NAG-ST) was found to be predominantly associated with the periplasmic extract (about four-fold higher than the culture supernatant) of a recombinant E. coli (JM109) strain carrying the NAG-ST toxin gene. Four molecular species of NAG-ST, two each from the periplasmic extract and culture supernatant of JM109, were purified. Amino acid sequence analysis of the four NAG-ST peptides isolated by HPLC revealed that they all differed from that of the mature 17-amino acid residue NAG-ST released by V. cholerae non-O1. The M(r)-values of the peptides obtained from the periplasmic extract were 4331 and 2785, while those recovered from the culture supernatant were 3154 and 2785. It thus appears that V. cholerae NAG-ST is synthesized as larger molecules in the recombinant E. coli strain. The differences in sizes of the exported NAG-ST molecule could relate to differences in the enzyme cleavage system between E. coli and V. cholerae.

Amino Acid Sequence↗
PubMed1993

Assessment of enterotoxin production by Yersinia enterocolitica and identification of a novel heat-stable enterotoxin produced by a noninvasive Y. enterocolitica strain isolated from clinical material.

Twenty-eight clinical isolates of Yersinia enterocolitica were investigated for their abilities to produce heat-stable enterotoxin (YST). All 21 invasive strains (serogroup O3 biotype 4) carried the previously described gene for YST (yst), with toxin detectable in culture supernatants from 20 strains. One of seven noninvasive, biotype 1A strains also had enterotoxic activity, despite failure to hybridize with a probe for yst. The toxin produced by this noninvasive (serogroup O6) strain resembled YST in terms of molecular size, heat stability, and solubility in methanol. It differed from YST, however, with respect to regulation of its production by temperature and its mechanism of action, which did not appear to involve cyclic GMP.

Animals↗
PubMed1993

[Study on the relationship between appearance of autoantibodies and chest X-ray findings of asbestos plant employees].

Antinuclear factor (ANA) and rheumatoid factor (RF) were determined in 220 employees of an asbestos plant. The relationship of the appearance of the two factors to sex, age, smoking habit, duration of asbestos exposure and asbestos exposure level was studied. In 207 employees who had chest roentgenograms, the relationship of these two factors to pulmonary lesions and pleural lesions was examined. Of the 220 employees, 33 (15%) had ANA and 7 employees (3.2%) had RF. ANA positive rate in the asbestos plant employees was significantly higher than in the control. Factors significantly correlated to their appearance could not be demonstrated. With the progress of pulmonary lesions the ANA positive rate significantly elevated, but ANA positive rate was not significantly correlated with pleural lesions. RF did not show any significant correlation with any of the factors.

Adult↗
PubMed1993

The technical problems shoot for the production of anti low molecular weight hapten antibody.

Four kinds of small molecular weight haptens, Desmosine, Adriamycin, 4'-carboxycotinine and 5'-Fluorouracil were used as the immunizing antigens to obtain rabbits polyclonal antisera. All of these haptenes were conjugated to Bovine Serum Albumin (BSA) using 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (EDCl) reagent. The functional amino or/and carboxyl group in hapten molecules was utilized for conjugation with BSA by EDCl reagent. The hapten conjugated with BSA was mixed with Freund's Complete or Incomplete Adjuvant, and immunized to rabbits abdominal subcutaneous regions. More than 3 times immunized rabbit's antisera were evaluated the titer, and the specificity was investigated by ELISA method. The specific antisera against desmosine and adriamycin were produced. Anti-desmosine antibodies had no cross-reaction to molecular structure resemble pyridinoline. Anti-adriamycin antibodies reacted well to adriamycin and it could distinguish the differences of -epi type of adriamycin. The ELISA assay systems used here had such sensitivity. However the specificity possessing antisera against 4'-carboxycotinine and 5-Fluorouracil could not produce even though the antisera titers were elevated. The reasons why and what kinds of problems were there are discussed in this paper. For the production of the specific affinity possessing antisera, the length and distance between the carrier protein and the hapten and the shape of the functional groups were the important factors for production of the specific antisera which recognize free form hapten molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Interleukin-1 beta production by alveolar macrophages in cases of asbestos exposure].

In order to investigate the role of interleukin-1 beta secreted by alveolar macrophages in the pathogenesis of pulmonary asbestosis, we performed bronchoalveolar lavage on 12 asbestos-exposed subjects and 10 control subjects, and measured interleukin-1 beta secreted by alveolar macrophages. Interleukin-1 beta production was increased in the asbestos-exposed subjects compared to control subjects (3.1 +/- 2.2 ng/ml versus 0.8 +/- 0.4 ng/ml, p < 0.05). The period after retirement was inversely correlated with interleukin-1 beta production (r = -0.67, p < 0.05). We divided non-smoking asbestos-exposed subjects into two subgroups based on the radiographical profusion according to the ILO classification. The advanced group was defined as grade 2 or greater profusion, and the early group was defined as grade 1 or lower profusion. We found higher production of IL-1 beta in the early group than in the advanced group.

Aged↗