Biomedical subjects

R Chiba

Publications and source records attributed to R Chiba.

At least 19 recordsLinked to original sources

PubMed2001

Effects of dermatan and dextran sulfates on arginine amidase activity released from isolated rabbit arteries.

We examined the levels of arginine amidase secreted from isolated rabbit arteries treated with dermatan and dextran sulfates, and the relation between the secretion of arginine amidase activity and the concentration of dermatan sulfate added to these arteries. The results showed that while dextran sulfate tended to accelerate the release of arginine amidase activity from the isolated rabbit ear artery, the induction was not significant. There was a significant increase in the level of arginine amidase released from the lower portion of isolated rabbit aorta (p<0.05), but no significant change in the upper portion of the aorta. In contrast, the addition of dermatan sulfate significantly increased the level of arginine amidase activity released from the isolated rabbit ear artery and the upper and lower portions of the aorta (p<0.05). Linear dose-response relationships were observed between the level of arginine amidase activity released from the isolated rabbit ear artery and aorta and the concentration of dermatan sulfate added.

Animals↗

PubMed2001

[A case of systemic lupus erythematosus with hemophagocytic syndrome and cytophagic histiocytic panniculitis].

A 23-year-old man, admitted because of high fever, polyarthralgia, butterfly rash and chest pain, was diagnosed as systemic lupus erythematosus (SLE) from the findings of positive antinuclear antibody and anti-DNA antibody. He was treated with 60 mg prednisolone daily, but as reducing the dose, white blood cell counts and platelet counts were decreased and fever, polyarthralgia, decrease of complements, increase of ferritin, hepato-splenomegaly and liver dysfunction were observed. Bone marrow specimen revealed phagocytosis of blood cells by histiocytes and he was diagnosed as hemophagocytic syndrome(HPS) due to active SLE. Methylprednisolone pulse therapy was effective temporarily, HPS recurred while reducing steroid, and cyclosporin was added. After a temporary remission, marked extensive swelling in the face appeared suddenly. Facial skin biopsy showed necrosis of fat cells and hemophagocytosis by histiocytes. Accordingly, he was diagnosed as panniculitis due to HPS and was treated successfully with intravenous cyclophosphamide pulse therapy and high dose of gammaglobulin. Several cases of HPS due to SLE have been reported recently, but this is a rare case of cytophagic histiocytic panniculitis (CHP) due to SLE.

Adult↗

PubMed2000

Genes encoding nitrilase-like proteins from tobacco.

Nitrilase (nitrile aminohydrolase, EC 3.5.5.1) catalyzes the hydrolysis of indole-3-acetonitrile (IAN) to indole-3-acetic acid (IAA). Arabidopsis thaliana genome has four nitrilase genes (NIT1, NIT2, NIT3 and NIT4). Three (NIT1, NIT2 and NIT3) of the four genes have high similarity. We have cloned two NIT4 homologs (TNIT4A and TNIT4B) from tobacco (Nicotiana tabacum). Genomic Southern hybridization, among other experiments, strongly suggests that tobacco has NIT4 homologs but not NIT1 to NIT3 homologs. Introduction of Arabidopsis NIT2 into tobacco conferred IAN-mediated growth inhibition, probably due to hydrolysis of IAN to IAA, while ectopic expression of TNIT4A had little effect on the sensitivity of transgenic plants to IAN. Nitrilase activity of TNIT4 proteins is discussed.

Amino Acid Sequence↗

PubMed1999

Ligation of CD31 (PECAM-1) on endothelial cells increases adhesive function of alphavbeta3 integrin and enhances beta1 integrin-mediated adhesion of eosinophils to endothelial cells.

We determined the role of the heterophilic interaction of alphavbeta3 integrin on endothelial cells with CD31 on leukocytes in mediating leukocyte-endothelial cell interactions. Preincubation of interleukin-4 (IL-4)-stimulated human umbilical vein endothelial cells (HUVECs) with anti-CD31 monoclonal antibodies (MoAbs) enhanced eosinophil adhesion to the IL-4-stimulated HUVECs, and the endothelial CD31-induced enhancement of eosinophil adhesion to IL-4-stimulated HUVECs was prevented by anti-vascular cell adhesion molecule-1 (VCAM-1) MoAb and anti-very late activation antigen-4 (VLA-4) MoAb, but not by anti-intercellular adhesion molecule-1 (ICAM-1) MoAb, anti-lymphocyte function-associated antigen-1 (LFA-1) MoAb, anti-P-selectin MoAb, or anti-E-selectin MoAb. CD31 stimulation of HUVECs increased the adhesive function of alphavbeta3 integrin to its ligand RGD peptide, the binding of which reached a maximum at 10 minutes after the stimulation, and the CD31-induced alphavbeta3 integrin activation on HUVECs was inhibited by inhibitors of protein kinase C and phosphatidylinositol 3 kinase (PI3-kinase). Furthermore, anti-alphavbeta3 integrin MoAb and RGD peptide as well as soluble CD31 inhibited endothelial CD31-induced enhancement of eosinophil adhesion to IL-4-stimulated HUVECs. However, anti-alphavbeta3 integrin MoAb had no significant inhibitory effect on the eosinophil adhesion to IL-4-stimulated or unstimulated HUVECs without CD31 stimulation of HUVECs. Finally, CD31 stimulation of eosinophils increased the adhesive function of alpha4beta1 integrin (VLA-4) to its ligand fibronectin and their adhesion to IL-4-stimulated HUVECs in a VLA-4-dependent manner. These results indicate that CD31-mediated inside-out signaling activates alphavbeta3 integrin on endothelial cells, that the heterophilic alphavbeta3 integrin/CD31 interaction induces beta1 integrin-mediated adhesion of eosinophils to endothelial cells, and that the heterophilic interaction itself is not significantly involved in firm adhesion of eosinophils to endothelial cells.

Antibodies, Monoclonal↗

PubMed1999

Total number and size distribution of hepatic metastases of carcinoma.

OBJECTIVE: To quantify the susceptibility of carcinoma to hepatic metastases by studying autopsy livers with carcinoma metastases, the primary sites of which were mostly the digestive organs. STUDY DESIGN: We developed a stereologic method of estimating the total number, N, and the size distribution of metastatic tumors in the liver based on a geometric model of spherical nodules with varying radii, r. This method proved to be sufficiently reliable by disector analysis simultaneously performed in some cases; it gave an approximate result. This method was applied to the 31 autopsy cases. Correlation and regression analyses were performed among N, the mean radius of nodules, rmean, and conventional pathologic features of the primary tumor. RESULTS: The estimates of N ranged from 10 to 3.2 x 10(5). A close negative correlation was confirmed between N and rmean. Neither significant correlation nor regression was observed among N and the other pathologic factors of the primary tumors. CONCLUSION: N turned out to serve as a useful index for evaluating the metastatic potential of a carcinoma. However, investigation has yet to be made to determine biologic factors in the primary tumor closely associated with N.

Carcinoma↗

PubMed1998

Cross-linking of intercellular adhesion molecule-1 induces interleukin-8 and RANTES production through the activation of MAP kinases in human vascular endothelial cells.

We investigated whether intercellular adhesion molecule-1 (ICAM-1) transduces outside-in signals for the production of chemokines IL-8 and RANTES in endothelial cells. Cross-linking of ICAM-1 induced IL-8 and RANTES mRNA expressions and increased their protein synthesis and secretions in endothelial cells. Furthermore, ICAM-1 cross-linking activated 44- and 42-kDa mitogen-activated protein (MAP) kinases (ERK1 and ERK2) in endothelial cells, as indicated by the electrophoretic mobility shift of MAP kinases on SDS-polyacrylamide gels. Finally, the specific MEK inhibitor PD98059 inhibited ICAM-1-induced IL-8 and RANTES production in endothelial cells. Taken together, these results indicate that stimulation of ICAM-1 induces IL-8 and RANTES production through the activation of 44- and 42-kDa MAP kinases in endothelial cells, suggesting that ICAM-1-induced chemokine production in endothelial cells would further attract and activate leukocytes to induce intense inflammation.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1998

Effects of Nd:YAG laser irradiation on morphometry and lung function in elastase-induced emphysema in rats.

BACKGROUND & OBJECTIVE: Although thoracoscopic laser ablation therapy has been hailed as an effective surgical treatment for diffuse emphysema, no one has as yet made an in-depth study of the efficacy of this treatment. This investigation was undertaken to research the effects of laser pneumoplasty on an animal model of emphysema. STUDY DESIGN/MATERIALS AND METHODS: Eight weeks after elastase treatment, the rats' left lungs were irradiated using contact Nd:YAG laser. Pulmonary function tests were performed 4 weeks after irradiation and the lungs were prepared for histologic examination. RESULTS: Dense fibrous scars beneath the pleura were observed at 4 weeks after irradiation. Although mean linear intercept values of irradiated lungs were not much lower than those in the non-irradiated elastase-treated group, laser irradiation caused a significant decrease in lung volume. While there was no significant difference in quasistatic compliance, elastic recoil pressure of the lung increased to control levels at total lung capacity volume. CONCLUSION: We conclude that laser therapy does not cause normalization of compliance, or improvement in the deeper part of the emphysematous lung, but rather a peripheral volume reduction and "encasement effect" on the lungs as a result of fibrotic scars.

Analysis of Variance↗

PubMed1997

Two-D distance distribution analysis: an application to HBcAg-positive hepatocytes and its relation to septum formation in cirrhosis.

The morphogenesis of cirrhotic septa in chronic hepatitis B was studied assuming that they arise at the sites of hepatocellular necrosis invoked by host immune reaction against HBcAg-expressing hepatocytes. Sections from three livers with chronic hepatitis B, all in cirrhotic stage, were immunostained with HBcAg and subjected to morphometry to analyze the distribution of HBcAg(+) hepatocytes and its relation with septa. HBcAg(+) cells were not distributed randomly over the nodules but forming focal areas. The septum formation along these foci was shown by 2-D distance distribution analysis, a technique we devised. Upon a sheet of color microphotograph of immunostained section, hundreds of test points each 400 microns apart were arranged by overlaying a tessellated grid. From each of the points hitting the nodules, the distance to the nearest nodulo-septal border D(min) was measured. Measurement was performed on a total of 2,585 test points. It was shown that the mean D(min) in the HBcAg(+) areas was significantly smaller than in HBcAg(-) areas. Thus, the cirrhotic septa are considered to arise at the places of HBcAg(+) foci, connecting them by postnecrotic collapsing.

Chronic Disease↗

PubMed1996

Atypical adenomatous hyperplasia and adenocarcinoma of the human lung: their heterology in form and analogy in immunohistochemical characteristics.

BACKGROUND: In a previous study, morphometry and multivariate cluster analysis was performed on 97 lesions. These consisted of atypical adenomatous hyperplasia (AAH), considered to be an important lesion corresponding to a step of carcinogenesis for adenocarcinoma of the human lung, Clara cell type, and type 2 pneumocyte type adenocarcinomas. Although AAH and the two types of adenocarcinoma were re-classified into three clusters and AAH was defined in clear morphologic terms, the biologic nature of AAH has yet to be clarified. In the present study, immunohistochemical analysis was performed to gain a deeper understanding of the relationship between AAH and the two types of adenocarcinoma, and to compare the results with those obtained by morphometry. METHODS: The 97 lesions analyzed by morphometry were submitted to immunohistochemical analyses using antibodies against surfactant apoprotein A, urine protein 1, carcinoembryonic antigen and cytochrome P-450s (1A1-2, 2B1-2, 2E1). Also examined, as controls, were 17 lesions with adenomatous hyperplasia (AH), a non-neoplastic reactive change of bronchiolo-alveolar cells, 30 areas of normal Clara cells, and 36 areas of normal type 2 pneumocytes. The immunoreactivity was graded by introducing a semi-quantitative scoring system. RESULTS: Immunohistochemically, AAHs behaved quite similarly to the lesions classified as Clara cell type or type 2 pneumocyte type adenocarcinomas. For any of the antibodies employed, no significant difference in immunoreactivity was demonstrated among these lesions. CONCLUSIONS: The results suggest, in accordance with our previous morphometry, that AAH is a lesion closely related with Clara cell type and type 2 pneumocyte type adenocarcinomas, probably as their common precursor. However, the two types of adenocarcinomas, despite their characteristic morphologic features, are indistinguishable using the biological indicators applied in this study.

Adenocarcinoma↗

PubMed1996

Papillary adenoma of type II pneumocytes might have malignant potential.

Papillary adenoma of type II pneumocytes is a rare tumour. It is considered to be a benign neoplasm and is derived from immature cells in the bronchioloalveolar epithelium, however, its biological nature has not been elucidated. We report a case of an adenomatous tumour; a papillary adenoma of type II pneumocytes, which we regard as possessing malignant potential. Light microscopically, as well circumscribed, papillary tumour of predominantly cuboidal cells resembling type II pneumocytes was found, but Clara type and ciliated cells were also present. Immunohistochemically, the tumour cells reacted positively with antibodies to surfactant apoproteins (A, B), carcinoembryonic antigen, cytochrome P-450 1A1-2 and 2B1-2. Ultrastructurally, many osmiophilic lamellar bodies and electron-dense granules were demonstrated. Semi-serial sections revealed signs of transbronchial dissemination and vascular invasion. Morphometry using 12-dimensional cluster analysis disclosed features of the tumour cells which resembled those of pneumocyte type II adenocarcinoma. These findings suggest that the present case has some malignant characteristics and originates from immature bronchiolar or alveolar cells, with a potential to develop into both type II pneumocyte and Clara cell type adenocarcinomas.

Adenoma↗

PubMed1996

[Histological effects of short term endocrine therapy on prostatic cancer].

BACKGROUND: The objective of this study is to investigate the pathological changes which occurred in prostatic cancer shortly after the commencement of endocrine therapy. METHODS: Fourty-three patients underwent radical prostatectomy immediately after the short term endocrine therapy (treatment period was within one month) and the histological pictures of operative specimens were compared to those obtained from the pretreatment biopsy specimens. RESULTS: Degenerative changes of cancer cells, such as nuclear and cytoplasmic vacuole, collapse of the cytoplasm and the appearance of naked hyperchromatic nucleus were noticed after the short term endocrine therapy. Especially in the cases which were histologically evaluated to be poorly differentiated in the biopsy specimens, not only degenerative changes but also destruction of cancer nests caused by cell death were observed. The histological effects affected by short term endocrine treatment had no relation to the prognosis, but in the cases of stage D2, the pathological grade judged by post-therapeutic specimens were found to be useful for the prediction of prognosis. CONCLUSION: Endocrine therapy induces remarkable pathological changes in prostatic cancer within a very short time after beginning treatment.

Aged↗

PubMed1995

Computer-assisted pathology of intraepithelial adenocarcinoma and related lesions: 3-D distribution, structural aberration and discrimination.

To discriminate among intraepithelial neoplasms, we have been relying on tissue microscopy, but pathologists' subjectivity sometimes impairs diagnosis. Even an individual pathologist is sometimes unable to reproduce exactly his or her own previous diagnosis. Are various atypical lesions classifiable in a reproducible way, and if they are, how? The reliability of a diagnosis will be strengthened if we can define the "natural" categories inherent in cells and tissues. Morphometry and statistical analysis using a computer can provide answers. Atypia, a morphological feature of carcinoma, is essentially multivariate. Quantification of a tissue feature requires reducing it to a set of ten or more quantities, including size, shape and position of the nucleus, nucleolus, and the cell itself. The grade of aberration from the norm can be assessed only by a synthetic approach, using a computer for multivariate cluster analysis. This classification has been attempted in adenocarcinoma and related lesions of the lung and pancreas. The categories thus established are reproducible, because the lesions fall into divisions according to their forms. We can also examine the organ distribution of intraepithelial neoplasms by three dimensional (3-D) computer-assisted mapping. To reach a higher level of reliability, as many meaningful features as possible should be taken into account. Particularly, we emphasize the significance of architectural pattern as a biomarker for intraepithelial glandular neoplasms. Computer-aided 3-D structural analysis visualizes the basic skeleton of these neoplasms around which the cells adhere. Instead of the dichotomous tree pattern of normal glands, the tumors basically harbor a 3-D network, tubular or porous, which increasingly deviates from the norm along with the transition from adenoma to well to moderately to poorly differentiated adenocarcinoma. This structural aberration, if recognizable on 2-D sectional images, will serve as a surrogate endpoint biomarker for glandular tumors.

Algorithms↗

PubMed1995

Quantitative cytopathology of endometrial lesions.

Morphometric and multivariate statistical methods were used to discriminate endometrial carcinoma from benign cells in cytologic studies. Clumps of epithelial cells that appeared most diagnostically relevant were selected from aspirated samples of 70 endometrial cancer patients. The cells' cytologic character was reduced to a combination of five quantitative parameters--nuclear size, degree of anisokaryosis, nuclear from index, homogeneity of nuclear chromatin texture, and regularity of nuclear arrangement. The 5-variate cluster analysis demonstrated that the 70 cases could be classified into three definite groups: Group A (17 cases) was characterized by cells of small nuclear size, slight anisokaryosis, homogeneous chromatin texture, and regular nuclear arrangement; Group C (12 cases) by cells of large nuclear size, marked anisokaryosis, heterogeneous chromatin texture, and irregular nuclear arrangement; and Group B (41 cases) by cells of intermediate parameter values. Group C was derived from 10 cases of adenocarcinoma and 2 of atypical hyperplasia, while Groups A and B were not derived from any cases of malignancy. The computer-assisted morphometric statistical method can objectively classify the endometrial cells into malignant and benign, with improved validity and reproducibility. The cytopathologic finding, if detected by this method, may serve as a surrogate endpoint biomarker.

Cluster Analysis↗

PubMed1994

Quantitative morphology of human cirrhotic livers. Part I: Parameter expression of pattern as a basis for computerized classification.

Although classification is a long-used method of histopathology, a reproducible one has yet to be created. We established a most adequate classification of cirrhosis from a geometric and statistical point of view, by reducing its form to a set of quantities and submitting the data to multivariate analysis. In this article, methods for quantification are described as a preliminary step for the statistical treatment that appears in another paper. The pattern was reduced to a set of four quantities: (i) the mean nodular radius; (ii) the coarseness; (iii) the mean septal thickness; and (iv) the degree of nodular separation. A model of dispersed spheres with various radii r was employed to assimilate cirrhosis; r was assumed to follow a logarithmic normal distribution. The parameters of this distribution were estimated stereologically from measurements on microscopic sections of chord lengths lambda generated from nodules by a test line. The coarseness was defined as the volume % of nodules larger than 1.5 mm in r. The mean septal thickness was determined stereologically on a plate model, into which the actual septa were transformed without changing their volume or surface density. The degree of nodular separation p theta was defined as a two-dimensional parameter, based on the curvature of nodulo-septal borders. It was demonstrated in several examples how accurately a set of these quantities describes various patterns of cirrhosis.

Humans↗

PubMed1994

Quantitative morphology of human cirrhotic livers. Part II: The statistically adequate morphological classification of liver cirrhosis. Multivariate analysis from quantified data of form.

In a previous report, we developed methods by which to quantify various patterns of cirrhosis. A set of parameters were used: (i) the mean nodular radius; (ii) the coarseness; (iii) the mean septal thickness; and (iv) the degree of nodular separation. This was applied to 70 cirrhotic livers in an attempt to establish a reproducible classification, and the data were subjected to four-dimensional cluster analysis (Ward method) using a mainframe computer. Five clusters appeared: cluster A, fine nodules, thin septa; cluster B, coarse nodules, relatively thin septa; cluster C, fine nodules, thick septa; cluster D, extremely coarse nodules; and cluster E, coarse nodules, thin septa and incomplete nodulation. Of these, cluster A was considered to correspond to the nutritional type of Gall, cluster B to posthepatitic type (Nagayo's Type B), cluster C to postnecrotic type (Nagayo's Type A) and cluster E to the subtype of posthepatitic cirrhosis with incomplete nodulation (Miyake's Type BI). Cluster D comprised cases with extremely coarsened nodules. The reproducibility of this clustering was fully ensured by linear discriminant analysis. Another discriminant analysis, the canonical, allowed us to visualize the separation of clusters in a two-dimensional (2-D) scatter diagram. We thus managed to establish a most adequate classification from a geometric and statistical point of view.

Humans↗

PubMed1994

[Flow cytometric analysis of prostatic adenocarcinomas after hormone therapy].

A DNA ploidy pattern of prostatic adenocarcinoma was studied by flow cytometry using the formalin-fixed, paraffin-embedded tissues obtained from 65 patients. These patients received hormone therapy preoperatively. Forty cases (61.5%) showed a diploid pattern, and 25 (38.5%) an aneuploid pattern. Comparing this ploidy pattern with histological classification, the aneuploid pattern was found in 13 cases (52%) of poorly differentiated group, 12 cases (48.0%) of moderately differentiated group and 0 case (0%) of well differentiated group. Thus, rate of aneuploid pattern increased with an increase in the grade of malignancy. Five years survival rate was 62.6% in the diploid group while it decreased to 30.9% in the aneuploid group. There was a significant difference between the two groups. In 23 cases with stage D, the ploidy pattern of primary region could be compared with that of metastatic region (lymph nodes). The prognosis of patients who exhibited the aneuploid pattern in metastatic region was significantly worse than that of other patients. These data suggested that flow cytometric DNA analysis of prostatic cancer materials after hormone therapy also produces meaningful information in predicting the prognosis of prostatic cancer.

Adenocarcinoma↗

PubMed1994

Morphometric and multivariate statistical detection of cancer cells in endometrial cytology.

Endometrial carcinoma was discriminated in cytologic studies using morphometric and multivariate statistical methods. On aspirated samples from 70 cases (10 well-differentiated adenocarcinomas, 4 hyperplasias and 56 normal controls), clumps of epithelial cells that could be regarded as the most diagnostically relevant were selected in each case. Their cytologic character was reduced to a combination of five quantitative parameters (nuclear size, degree of anisokaryosis, nuclear form index, homogeneity of nuclear chromatin texture and regularity of nuclear arrangement). The five-variate cluster analysis demonstrated that the 70 cases could be classified into three groups: group A (17 cases) was characterized by cells with small nuclear size, slight anisokaryosis, homogeneous chromatin texture and regular nuclear arrangement; group C (12) by cells with large nuclear size, marked anisokaryosis, heterogeneous chromatin texture and irregular nuclear arrangement; and group B (41) by cells with intermediate parameter values. Group C was derived from 10 cases of adenocarcinoma and 2 of atypical hyperplasia, while groups A and B were not derived from any cases of malignancy. This preliminary study indicated that morphometric-statistical classification can be of great help in improving the cytodiagnostic validity and reproducibility of endometrial carcinoma, and it awaits further, practical testing within a significantly larger series of malignancy cases.

Adenocarcinoma↗

PubMed1994

[Morphometrical and statistical detection of cancer cells].

Morphometrical and multivariate statistical methods were applied to detection of carcinoma cells in cytologic studies. A total of 70 clumps of epithelial cells were selected from endometrial samples (10 adenocarcinomas, 4 hyperplasias and 56 normal controls), and their cytologic characters were reduced to a combination of five quantitative parameters (nuclear size, degree of anisokaryosis, nuclear from index, homogeneity of nuclear chromatin texture and regularity of cellular arrangement). The 5-variate cluster analysis demonstrated that the 70 clumps could be classified into three definite groups; A(17), B(41), and C(12). Group C, characterized by cells of large nuclear size, marked anisokaryosis, heterogeneous chromatin texture and irregular cellular arrangement, was derived from 10 samples of adenocarcinoma and 2 hyperplasia, while Groups A and B were not derived from any malignant samples. In conclusion, morphometrical-statistical classification can be of great aid in improving the cytodiagnostic validity and reproducibility.

Adenocarcinoma↗