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Biomedical subjects

H Ohtani

Publications and source records attributed to H Ohtani.

At least 181 records · Page 10Linked to original sources

[Production of inflammatory markers by HepG 2 cells stimulated with monocyte conditioned media: the effects of corticosteroid and other immunosuppressants].

Both C-reactive protein (CRP) and serum amyloid A protein (SAA) are determined as an indicator of inflammation and tissue damage. We found that CRP decreased extremely after administration of corticosteroid but SAA did not. However, the mechanism of the CRP decrease by corticosteroid therapy is unclear. In this study we have examined the effects of some immunosuppressive drugs and cytokines on the production of CRP and SAA by human hepatoma cells (HepG 2). A corticosteroid prednisolone did not enhance the production of CRP by HepG 2 cells but enhanced that of SAA, which indicate that prednisolone had no direct effect on the CRP production. Some immunosuppressants other than corticosteroids suppressed the SAA production but had no effect on the CRP production. IL-1 beta induced both CRP and SAA production but only in the co-presence of IL-6. A cytokine IL-6 induced the CRP production in the presence of IL-1 beta, but did not affect the constitutive production of SAA. Then we have examined the cytokine production by monocytes stimulated by lipopolysaccharide. Prednisolone inhibited the production of IL-1 alpha, IL-1 beta, IL-6 and TNF alpha.

Animals↗

[Studies on alpha 2 macroglobulin deficiency in association with cancer metastasis].

We found 5 cases of prostatic carcinoma with metastasis with alpha 2 macroglobulin (alpha 2 M) concentration below approximately 40 mg/dl in serum. All these patients had bone metastasis, and none of them had DIC. We found no other cases with such a low concentration of alpha 2 M. Their alpha 2 M level increased to normal level after treatment with transurethral resection of prostate or hormone agents, and the level was correlated with the clinical symptom. During the clinical course, their alpha 2 M level was negatively correlated with prostate-specific antigen (PSA) and prostatic acid phosphate (PAP). All these results suggest that alpha 2 M concentration in serum reflects the severity of prostatic carcinoma with metastasis and that alpha 2 M deficiency is an indicator of metastasis. The acute phase proteins of CRP and serum amyloid A did not increase in spite of the presence of metastasis in these patients with extremely low alpha 2 M level (< 20 mg/dl), suggesting that alpha 2 M is involved in the metabolism of these acute phase proteins. On immunohistochemical studies, their specimens of prostatic carcinoma gave positive stain for PSA and urokinase-type plasminogen activator (u-PA). Both PSA and u-PA formed a complex with alpha 2 M in vitro. The alpha 2 M deficiency in these patients might be due to the complex formation between alpha 2 M and these prostate-originated proteases and to the rapid disappearance of the complex.

Aged↗

Transarterial infusion of cisplatin and doxorubicin in bladder cancer.

Forty-five patients (median age 63 years) with muscle invasive bladder cancer were treated with transcatheter intraarterial infusion (TAI) of cisplatin (CDDP) and doxorubicin. They received a total of 114 courses (median 3 courses per patient) of TAI. Complete response was obtained in 20 patients (44%), partial response in 17 (38%), stable disease in 6(13%), and progression of disease in 2 patients (5%). The overall response rate was 82% at a median follow-up of 36 months. The actuarial survival of the patient population was 72% at 5 years; 36 patients were alive and 9 had died of cancer progression. The treatment was generally extremely well tolerated without major complications. The current study also revealed the fact that papillary carcinomas were more sensitive to this therapy than were non-papillary tumors. Overall, response rate and local control were significantly higher in low-grade than in high-grade tumors. The observed high complete response and good survival rate suggest that intraarterial CDDP and doxorubicin might be highly effective for localized invasive bladder cancer.

Adult↗

[Lipoprotein(a) concentrations and apolipoprotein(a) phenotype frequencies in cord blood of newborn infants and sera of children in Japan].

Lipoprotein(a) [Lp(a)] is considered to be an additional, independent, and largely genetically risk factor for the development of premature coronary heart disease. We measured Lp(a) levels and apo(a) phenotype in cord blood samples from 140(72 males, 68 females) Japanese newborn infants, and those in serum samples from seventy-nine normolipidemic out-patient children from the pediatrics. In the present study, we determined the relations between cord blood Lp(a) levels and apo(a) phenotypes. Maternal age, gestational age, weight and height were analyzed as covariates. The distribution of Lp(a) levels in cord blood was highly skewed towards the lower levels, as previously described. The mean Lp(a) concentration was 4.6 mg/dl(SD of 2.22 mg/dl) and median of 4.0 mg/dl, approximately three-fold lower than that observed in Japanese adult subjects. We did not find differences in the mean and median cord blood Lp(a) levels between male and female. Phenotyping of apo(a) was performed for 140 sera. The mean Lp(a) level in the B type was almost three times higher than that for the S4 type. A strong inverse relationship was found between the apparent molecular weight of apo(a) isoforms and serum Lp(a) concentration. The concentrations of Lp(a) reached to adult levels within first five years of life.

Adult↗

Copper-62-ATSM: a new hypoxia imaging agent with high membrane permeability and low redox potential.

UNLABELLED: An ideal hypoxia imaging agent should have high membrane permeability for easy access to intracellular mitochondria and low redox potential to confer stability in normal tissue, but it should be able to be reduced by mitochondria with abnormally high electron concentrations in hypoxic cells. In this context, nitroimidazole residues are not considered to be essential. In this study, Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM), a 62Cu-bisthiosemicarbazone complex, with high membrane permeability and low redox potential, was evaluated as a possible hypoxia imaging agent, using electron spin resonance spectrometry and the Langendorff isolated perfused rat heart model as well as rat heart left anterior descending occlusion model. METHODS: Nonradioactive Cu-ATSM was incubated with rat mitochondria, after which reduction of Cu(II) to Cu(I) was measured with electron spin resonance. As a model of hypoxic mitochondria, rotenone (Complex I inhibitor)-treated mitochondria were used. RESULTS: In this study, Cu-ATSM was reduced by hypoxic but not by normal mitochondria. CONCLUSION: Thus, retention of 62Cu-ATSM was studied serially in perfused rat hearts under conditions of normoxia (95% O2 + 5% CO2), hypoxia (95% N2 + 5% CO2) and reoxygenation (95% O2 + 5% CO2). In normoxia and reoxygenation, 62Cu-ATSM injected as a single bolus showed low retention (23.77% and 22.80%, respectively) 15 min after injection, but retention was increased markedly under hypoxic conditions (81.10%). Also, in the in vivo left anterior descending occluded rat heart model, 62Cu-ATSM retention was inversely correlated with accumulation of 201Tl, a relative myocardial blood flow marker.

Animals↗

Expression of costimulatory molecules B7-1 and B7-2 in macrophages and granulomas of Crohn's disease: demonstration of cell-to-cell contact with T lymphocytes.

The pathogenesis of Crohn's disease, an intractable inflammatory disease, involves impaired and/or excessive activation of mucosal macrophages and T lymphocytes. B7-1 (CD80) and B7-2 (CD86) molecules are costimulatory molecules that are indispensable to T-cell activation by antigen-presenting cells. To elucidate the roles and characteristics of these antigen-presenting cells in Crohn's disease, in situ localization of B7-1 and B7-2 (in relation to the distribution of T cells) was clarified by light and electron microscopic immunohistochemistry. The results were compared with those from a study of ulcerative colitis. Normal colonic tissue expressed B7-1 or B7-2 only sporadically. In active Crohn's disease, however, an increase in the number of B7-1/B7-2+ cells correlated with an increase in expression of HLA-DR and intercellular adhesion molecule-1. Most B7-1/B7-2+ cells were identified as noncaseating granulomas or as macrophages, which tended to form an aggregate especially in ulcer bases. In active ulcerative colitis, the increase of B7-1/B7-2+ cells was not as prominent as that in Crohn's disease. Double immunohistochemistry revealed a close cellular distribution between noncaseating granulomas and T cells. Immunoelectron microscopy confirmed the expression of B7-1/B7-2 along the plasma membranes of cytoplasmic processes of granuloma cells, where lymphocytes were closely attached. The present study suggested that granuloma formation in Crohn's disease is coupled with antigen presentation via a B7-1/B7-2-CD28 pathway, which may contribute to the pathogenesis of the disease.

Adult↗

[CREST syndrome].

Explore the source record for details and available documents.

Acute Kidney Injury↗

[Establishment of a laboratory information office in response to the expanding need for consultation--actual situation of the laboratory information room, Clinical Laboratory Department, Kitasato University Hospital].

Due to the advancement, segmentation and specialization of the medical care, laboratory examinations covered by the National Health Insurance (NHI) tariff have exceeded several hundred, and it is not possible for medical staff to be familiar with all of these and to utilize them appropriately. There is an urgent need for laboratory information for physicians, nurses, and other health professionals. Accordingly, our Clinical Laboratory Department, Kitasato University Hospital, established a "Laboratory Information (Consultation) Office" in July 1995 to provide consultations on clinical laboratory tests to those engaged in daily clinical practice and in medical research. The office is situated on the second floor of the Laboratory Building of the Kitasato University Hospital. One laboratory technician and one laboratory physician (clinical pathologist) are stationed there. They are available for telephone consultations from 9:00 to 17:00 on weekdays, except for holidays, and from 9:00 to 13:00 on the first, third and fifth Saturdays. In addition, since January 1997, this office also has been open to members of medical associations in various cities in our area. To cope with requests for laboratory information, including whether an examination is covered the NHI tariff, selection of appropriate screening examinations and availability of new laboratory tests, consultations by fax are accepted at any time, even after regular working hours. As a post-graduate education program, the clinical laboratory physicians study specimen handling analytical methods and interpretation of results. At medical staff meeting, personnel from the Laboratory Information Office provide clarification on the types of consultations offered, address complex questions and find resolutions for rarely encountered and difficult laboratory issues. At these meetings, a summary of new laboratory examinations also is presented. This system of an information office where full-time laboratory physicians and laboratory technicians are stationed is the first such attempt in Japan. It may be considered a pilot project to determine if such a system may be applied to other laboratory departments in the future.

Clinical Laboratory Information Systems↗

Expression of costimulatory molecules B7-1 and B7-2 by macrophages along invasive margin of colon cancer: a possible antitumor immunity?

Costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are indispensable for T-cell activation. Recently, a paucity of these costimulatory molecules was reported in inflammatory cells in colon cancer, which may permit the immune evasion of the cancer. The present study uses immunohistochemistry to reveal the expression of these molecules in 43 cases of colorectal cancer tissue. B7-2 was expressed in mononuclear calls distributed along the invasive margin in 37 of 43 cases. B7-1 was positive in the same area in 22 cases. In contrast, the expression of B7-1/B7-2 was usually inconspicuous in the stroma within cancer. Most B7-1+ and B7-2+ cells were identified as macrophages because of the coexpression of CD68 antigen or acid phosphatase activity. CD4+ or CD8+ T cells were distributed in the same area and were in close contact to B7-1/B7-2+ cells. Both CD4+ and CD8+ T cells had a proliferative activity with a labeling index of Ki-67 of 1.5% and 2.5%, respectively. Conventional electron microscopy confirmed both the accumulation of macrophages along the invasive margin and the attachment of lymphocytes to them. Immunoelectron microscopy confirmed: (a) localization of B7-2/B7-1 along the cell membrane; (b) abundance of vacuoles and heterophagosomes (a finding indicative of phagocytosis of other cells) in the cytoplasm of these cells; and (c) direct cell-to-cell contact between these macrophages and lymphocytes. The present data, which suggest that an immune reaction occurs along the invasive margin of colorectal cancer, are in accordance with previous clinicopathologic studies suggesting that peritumoral lymphocytic infiltration is one of the favorable prognostic factors in this disease.

Antigens, CD↗

Optimal configuration of pyrene excimer induced by the excimer-forming two-probe nucleic acid hybridization method.

Excimer-forming two-probe nucleic acid hybridization (ETPH) method with pyrene as a fluorophore enables homogeneous hybridization assays. We examined the effect of linker length between a pyrene residue and a terminal sugar moiety on Tm of hybrids in the presence of 20% dimethylformamide (DMF). The results including those of CD measurements indicated no interaction of pyrene residues with the duplex formed between a target 32-mer and a pyrenemethyliodoacetamide-introduced 16-mer probe (PMIA-P5)/a pyrenebutanoic acid-introduced 16-mer probe (PBuA-P3), which is the best pair of probes for intense excimer emission. This was also supported by a computer-assisted molecular modeling using Insight II and Discover software.

DNA↗

Primary structure of the novel bacterial rhodopsin from extremely halophilic archaeon Haloarcula japonica strain TR-1.

A novel bacterial rhodopsin was identified in Haloarcula japonica strain TR-1. The gene encoding the bacterial rhodopsin was cloned and sequenced. The structural gene consisted of an open reading frame of 750 nucleotides encoding 250 amino acids. The deduced amino acid sequence of the Ha. japonica bacterial rhodopsin showed the highest homology to those of cruxrhodopsins.

Amino Acid Sequence↗

Dual over-expression pattern of membrane-type metalloproteinase-1 in cancer and stromal cells in human gastrointestinal carcinoma revealed by in situ hybridization and immunoelectron microscopy.

Membrane-type metalloproteinase-I (MTI-MMP) is a transmembrane metalloproteinase, which activates pro-gelatinase A. There has been disagreement as to whether the cell types expressing MTI-MMP are cancer cells or stromal fibroblasts. Using human gastrointestinal carcinomas, the present study disclosed the tissue localization of MTI-MMP mRNA by in situ hybridization and ultrastructural localization of its protein by immunoelectron microscopy. In normal colon and stomach tissues, MTI-MMP mRNA and protein were negative or faintly positive both in epithelial cells and in stromal fibroblasts, except in the fundic gland of the stomach, which showed the positivity for MTI-MMP. In contrast, gastrointestinal cancer tissue showed over-expression of MTI-MMP mRNA and protein both in cancer cells and in stromal cells (fibroblasts). Stromal fibroblasts also expressed mRNA for gelatinase A and type-I procollagen. Double immunohistochemistry revealed that macrophages were also positive for MTI-MMP. Immunoelectron microscopy showed that MTI-MMP was localized along the plasma membrane of cancer cells and macrophages and in rough endoplasmic reticulum of fibroblasts. The present study reveals a dual over-expression pattern of MTI-MMP both in cancer cells and in stromal fibroblasts; the expression in cancer cells may be related to the invasive growth, whereas that in fibroblasts may be related to the tissue remodeling process caused by invasive growth of cancer cells.

Carcinoma↗

Quantitative determination of epinastine in plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for the quantitative determination of epinastine, a non-sedating histamine H1 receptor antagonist, in rat plasma, was developed. A 100-microliters volume of plasma sample was spiked with a solution of internal standard (diphenidol) and extracted with dichloromethane under alkaline conditions. The extract was applied onto the HPLC system and detected by ultraviolet absorption at a wavelength of 220 nm. The linearity of the calibration curve was preserved over the concentration range of 20-1000 ng/ml. Both intra-assay variation and relative error were less than 5% for the plasma containing 50 ng/ml or 1000 ng/ml of epinastine hydrochloride. The analytical method presented here should be useful for the investigation of the pharmacokinetic properties of epinastine, which is of clinical significance.

Animals↗

On-column isomerization of sugars during high-performance liquid chromatography: analysis of the elution profile.

Four monosaccharides (glucose, galactose, mannose and fructose) and one disaccharide (maltose) were subjected to high-performance liquid chromatography with UV or refractive index detection. Various profiles such as broad, tailed and splitted peaks were produced, depending on column temperature and eluent flow-rate because these saccharides underwent isomerization. In contrast, alpha-methylglucoside, a non-converting derivative, always produced a sharp peak. By analyzing these profiles kinetic constants of the isomerization were obtained and compared with the literature data.

Carbohydrates↗

Chondrocytes synthesize type I collagen and accumulate the protein in the matrix during development of rat tibial articular cartilage.

The present study was designed to investigate whether or not chondrocytes in articular cartilage express type I collagen in vivo under physiological conditions. Expressions of the gene and the phenotype of type I collagen were examined in rat tibial articular cartilage in the knee joint during development. Knee joints of Wistar rats at 1, 5, and 11 weeks postnatal were fixed in 4% paraformaldehyde with or without 0.5% glutaraldehyde and decalcified in 10% EDTA. After the specimens were embedded in paraffin and serial sections made, adjacent sections were processed for immunohistochemistry and in situ hybridization for type I collagen. The epiphysis of the tibia was composed of cartilage in week- 1 rats. Formation of articular cartilage was in progress in week 5 as endochondral ossification proceeded and was completed in week 11. Anti-type I collagen antibody stained only the superficial area of the epiphysis in week 1, but the immunoreactivity was expanded into the deeper region of the articular cartilage with development in weeks 5 and 11. Hybridization signals for pro-alpha 1 (I) collagen were seen in some of chondrocytes in the epiphysis of the week-1 tibia. The most intense signals were identified in chondrocytes in week 5 and the signals appeared weaker in week 11. The present study demonstrated that chondrocytes synthesize type I collagen and accumulate the protein in the matrix during development of the articular cartilage.

Age Factors↗

Localization of transforming growth factor-beta 1 precursor and latent TGF-beta 1 binding protein in colorectal adenomas.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine and is thought to be involved in colorectal tumorigenesis as a regulator of cell growth and differentiation. This role is mainly supported by in vitro studies while its role in vivo remains unclear. The aim of the present study was to investigate whether the TGF-beta 1 precursor (beta 1-LAP) and the latent TGF-beta 1 binding protein (LTBP) are expressed in colorectal adenomas, the presumed precursors of most of colorectal adenocarcinomas. TGF-beta 1 precursor and LTBP were examined in 35 adenomas and 10 normal colonic mucosa specimens by immunohistochemistry, using specific polyclonal antibodies. In normal colonic mucosa, beta 1-LAP was moderately expressed in epithelial crypt cells and in the stromal cells in the lamina propria. In adenomas, beta 1-LAP was localized in epithelial cells with an heterogeneous pattern and was also present in stromal cells around the adenomatous glands. LTBP was not detected in epithelial cells but was observed in stromal cells and in the extracellular matrix (ECM). beta 1-LAP expression in epithelial cells did not correlate with the grade of dysplasia, while LTBP localized in stromal cells and ECM appeared to be closely associated with areas of higher grade of dysplasia. This study is the first demonstration of both beta 1-LAP and LTBP in colorectal adenomas with different dysplasia grades. Our results suggest that TGF-beta 1 might be involved in the mechanisms controlling in vivo colorectal tumorigenesis and support a role for the stromal-associated TGF-beta 1.

Adenomatous Polyps↗

Structural differences between XX and ZW sex lampbrush chromosomes in Rana rugosa females (Anura: Ranidae).

In this study we investigated the morphology and pairing behavior of sex lampbrush chromosomes of XX and ZW females of Rana rugosa from five localities in Japan. Whereas lampbrush chromosomes of XX females from Hiroshima and Isehara had subterminally located centromeres and showed remarkable similarity, those of XX females from Hamakita had the centromeres in the middle. Analysis of landmark configurations revealed that chromosome Xq of Hamakita females closely resembled a part of Xq of Hiroshima and Isehara females, whereas Xp of Hamakita females was inverted compared with the other part of Xq of Hiroshima and Isehara females. Z chromosomes from Kanazawa and Niigata closely resembled the Hiroshima X, whereas the W closely resembled the Hamakita X. XX pairings from Hiroshima, Isehara, and Hamakita were found to be joined by one to four chiasmata at various points all along the axis in both the short and long arms, whereas chromosomal pairs from Kanazawa and Niigata showed only one chiasma between Zp and the distal region of Wq. From these findings we conclude that (1) both the W and the Hamakita X must have evolved from the more primitive Hiroshima and Isehara X chromosomes by a series of pericentric inversions; and (2) females distributed in Hamakita possess two X chromosomes similar to the W, suggesting that either sex-determining or sex-modifying genes on the Hamakita X are clearly different from those on the Kanazawa and Niigata W chromosome.

Animals↗