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Biomedical subjects

R M Nakamura

Publications and source records attributed to R M Nakamura.

At least 19 recordsLinked to original sources
PubMed2001

Laboratory tests for the evaluation of Helicobacter pylori infections.

Helicobacter pylori is a highly motile bacterium with multiple unipolar flagella, and it produces the urease enzyme. The flagella and urease are the virulence factors of H. pylori. H. pylori often establishes a chronic infection in the stomach that may lead to gastric and duodenal ulcers, gastric cancers, gastric lymphomas, and other gastrointestinal diseases. There are several different invasive and noninvasive clinical laboratory tests for H. pylori. Laboratory testing is not indicated in asymptomatic patients and should be considered only if treatment of H. pylori infection is planned. Invasive tests for H. pylori, such as tissue histology, culture, and rapid urease tests, are used if an endoscopy is performed on the patient. The noninvasive tests for H. pylori, such as enzyme antibody and urea breath tests, are recommended in patients whose symptoms do not warrant endoscopy. The urea breath test is very useful and is recommended to evaluate effectiveness in the eradication and treatment of H. pylori infections. Nucleic acid tests can complement other diagnostic procedures, and are useful in evaluating fixed biopsy tissue, environmental samples, gastric juices, oral secretions, and stool samples.

Anti-Bacterial Agents↗
PubMed2001

Aberrant expression of fetal RNA-binding protein p62 in liver cancer and liver cirrhosis.

p62 is a RNA-binding protein that was isolated by immunoscreening a cDNA expression library with autoantibodies from patients with hepatocellular carcinoma (HCC). This autoantigen binds to mRNA encoding insulin-like growth factor II, which has been found to be overexpressed in HCC and is tumorigenic in transgenic animals. Immunohistochemical analysis of HCC liver showed that 33% (9 of 27) exhibited readily detectable staining of p62 protein in the cytoplasm of all malignant cells in cancer nodules, whereas it was undetectable in adjacent nonmalignant liver cells. In addition one of two patients with cholangiocarcinoma expressed p62 in malignant bile duct epithelial cells. p62 expression was also detected in scattered cells in cirrhotic nodules in contrast to uniform expression in all cells in HCC nodules. In HCC nodules, p62 mRNA was also detected by reverse transcriptase-polymerase chain reaction analysis. Nine normal adult livers did not contain detectable p62 mRNA or p62 protein whereas five fetal livers were all positive for mRNA and protein. The observations show that p62 is developmentally regulated, expressed in fetal, but not in adult liver, and aberrantly expressed in HCC and could be playing a role in abnormal cell proliferation in HCC and cirrhosis by modulating expression of growth factors such as insulin-like growth factor II.

Adult↗
PubMed2001

Detection of active tuberculosis by an MPB-64 transdermal patch: a field study.

The mycobacterial antigen MPB-64 was formulated for delivery in a transdermal patch and used as a diagnostic skin test reagent to detect active tuberculosis (TB) in patients attending a clinic in Manila, The Philippines. The MPB-64 Transdermal Patch was applied to 62 patients, 49 with sputum-positive active disease and 13 who had completed TB chemotherapy, and to 28 non-TB but tuberculin-positive controls. The results were read at 72 h. The sensitivity of the Transdermal Patch was 87.8%, with an efficacy of 92.9% and a specificity of 100%. The 13 TB patients who had completed 6 months of TB chemotherapy showed different reactions to the MPB64 patch test: those who had completed chemotherapy < 4 months before testing were positive; 50% of patients who completed chemotherapy 5 months previously were positive; and those who had completed chemotherapy 7 and 8 months before were negative. All the non-TB controls with positive tuberculin tests were negative to the MPB-64 Transdermal Patch, even at the highest protein dose tested. This test may be a useful method to distinguish active TB patients from TB-infected but asymptomatic individuals. Moreover, the MPB64 Transdermal Patch may be useful to monitor successful chemotherapy.

Antigens, Bacterial↗
PubMed2001

Th1 adjuvant N-acetyl-D-glucosamine polymer up-regulates Th1 immunity but down-regulates Th2 immunity against a mycobacterial protein (MPB-59) in interleukin-10-knockout and wild-type mice.

Treatment of mice with heat-killed (HK) Mycobacterium bovis BCG or 1- to 10-microm chitin particles (nonantigenic N-acetyl-D-glucosamine polymers) is known to induce innate immune responses, including gamma interferon (IFN-gamma) production, which plays a Th1 adjuvant role. However, HK BCG further induces prostaglandin E2-releasing spleen macrophages (Mphi) (PGE2-Mphi), which potentially inhibit Th1 adjuvant activities. We found that chitin particles did not induce PGE2-Mphi formation. To further assess whether chitin has Th1 adjuvant effects, interleukin-10 (IL-10)-knockout (KO) mice and their wild-type (WT, C57BL/6) controls were immunized with a 30-kDa MPB-59 mycobacterial protein mixed with chitin. Immunization with MPB-59 alone induced Th2 responses, characterized by increases in total serum immunoglobulin E (IgE) and specific serum IgG1 levels and spleen Th2 cells producing IL-4, IL-5, and IL-10. No IFN-gamma-producing spleen Th1 cells, specific serum IgG2a, or delayed-type hypersensitivity (DTH) footpad reactions were detected. On the other hand, chitin-MPB-59 immunization significantly increased spleen Th1 responses, DTH reaction, and serum IgG2a levels along with decreases of Th2 responses. The magnitude of these Th1 adjuvant effects was greater in IL-10-KO mice than in WT mice. In contrast, immunization with HK BCG-MPB-59 showed little or no Th1 adjuvant effect. These data indicate that chitin has a unique Th1 adjuvant effect on the development of Th1 immunity against a mycobacterial antigen. IL-10 down-regulates the adjuvant effect of chitin.

Acetylglucosamine↗
PubMed2001

Serologic markers in inflammatory bowel disease (IBD).

Inflammatory bowel disease (IBD) is a generic term that refers to Crohn's disease and ulcerative colitis. Crohn's disease (CD) is a granulomatous enteritis which can involve the ileum, colon, and other parts of the intestinal tract. The serologic responses seen in Crohn's disease include antibodies to Saccharomyces cerevisiae, mycobacteria, bacteroides, listeria and E. coli. Many of these organisms may be involved in the pathogenesis of the Crohn's disease. Ulcerative colitis is characterized by inflammation of the mucosa and submucosa of the large intestine. The CD and UC are considered to be distinct forms of IBD; however, there is a subgroup of CD with a UC-like presentation. In recent years, several serologic markers have been found to be useful for the diagnosis and differentiation of CD and UC. These markers include the following antibodies (a) 2pANCA, (b) ASCA, (c) pancreatic antibody, and (d) OmpC antibody. The application of a panel of markers with the use of an algorithm can identify specific subtypes of IBD that have different clinical courses and progression of the diseases. The application of the serologic markers is useful for diagnosis and management of CD and UC patients.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Progress in the use of biochemical and biological markers for evaluation of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disorder which is predominant in females. The exact etiology remains undefined. Recently, a large number of biochemical and biologic markers, which are useful in the diagnosis, prognosis, and monitoring therapy of RA, have been reported. The new markers include genetic markers, filaggrin, citrulline containing peptides, A2/RA33, cytokines, joint and collagen breakdown products, and bone turnover markers. No laboratory tests in and of themselves are diagnostic of RA. The new markers have been employed in monitoring RA patients during treatment and following the course of the disease. With the development of innovative therapies for RA, many of the biochemical and biologic markers will be useful.

Acute-Phase Proteins↗
PubMed2000

Development of the antinuclear and anticytoplasmic antibody consensus panel by the Association of Medical Laboratory Immunologists.

The Association of Medical Laboratory Immunologists (AMLI) have developed a panel of antinuclear and anticytoplasmic antibody consensus sera that can be useful for enzyme immunoassay (EIA), Ouchterlony, and immunofluorescence assay methods. It was developed to assist in the evaluation of newly available EIA methods for the detection of autoantibodies. The panel of sera was evaluated in several clinical laboratories and a large number of laboratories owned by manufacturers of clinical autoantibody testing kits. The majority of sera performed well for the EIAs in both the clinical laboratories and the manufacturers' laboratories, but some samples had discrepant results. A major source of discrepancy is the current inability of the EIA results to be directly compared in a quantitative way as no standardization exists. The evaluation demonstrated lower sensitivity of detection by the Ouchterlony method. The limited evaluation of the sera with immunoblotting and Western blotting did not show good agreement with other methods. Further work must be done to standardize blotting methods prior to their use in routine clinical testing. The sera are now available to vendors and clinical laboratories for use in the detection of SS-A, SS-B, Sm, U1-RNP, Scl-70, Jo-1, double-stranded DNA, and centromere antibodies. The availability of the consensus sera will help evaluate and improve the EIA methods currently being used.

Antibodies, Antinuclear↗
PubMed2000

Effects of topical and oral vitamin E on pigmentation and skin cancer induced by ultraviolet irradiation in Skh:2 hairless mice.

This study investigates whether supplementation with topical RRR-alpha-tocopherol (Eol), topical RRR-alpha-tocopheryl succinate, and oral RRR-alpha-tocopheryl acetate can reduce the incidence of acute and chronic damage to the skin (i.e., sunburn and pigmentation and skin cancer, respectively) induced by ultraviolet (UV) irradiation to mice. Groups of twenty Skh:2 female hairless pigmented mice were treated with 1) lotion vehicle, 2) 5% Eol lotion, 3) 5% topical RRR-alpha-tocopheryl succinate lotion, or 4) lotion vehicle and oral RRR-alpha-tocopheryl acetate. Within each group, 15 mice were exposed to 0.24 J/cm2 of UV-B radiation three times per week. The animals' weights and food intakes were monitored, and the vitamin E concentrations of skin, liver, and adipose tissue were measured to determine whether the topical Eol resulted in significant tissue levels. Skin pigmentation was scored, and the total number of clinically detectable skin tumors per animal was counted weekly. Results showed that the skin concentrations of Eol, as well as levels in the adipose tissue, were increased after topical application. Mice treated with each form of vitamin E showed no signs of toxicity and had significantly less acute and chronic skin damage induced by UV irradiation, as indicated by reduced inflammation and pigmentation and by later onset and lesser incidence of skin cancer.

Administration, Oral↗
PubMed1999

Technology that will initiate future revolutionary changes in healthcare and the clinical laboratory.

Future trends in healthcare delivery will focus on preventive medicine that will require integration of molecular medicine with advanced information and computer technology. Molecular medicine will shift from costly intervention and treatment of established diseases to proactive prediction and prevention of disease risks. This approach will require new informatic systems that will link large scale databanks and special programs for data mining and retrieval in bioinformatics, cheminformatics, and population genetics. The clinical laboratory will soon be able to provide powerful new molecular diagnostic tools along with multianalytic assays for expression of genes and proteins in different patterns of diseases, disease progression, and predisposition to diseases.

Biotechnology↗
PubMed1998

Immunoregulatory roles of IL-10 in innate immunity: IL-10 inhibits macrophage production of IFN-gamma-inducing factors but enhances NK cell production of IFN-gamma.

In our study of the immunoregulatory roles of IL-10 in innate immunity, nonantigenic phagocytosable chitin particles were administered i.v. to IL-10-deficient (knockout (KO)) mice or KO mice pretreated with anti-NK1.1 or anti-IFN-gamma Abs. The results established that chitin treatment of KO mice increased superoxide anion release from alveolar macrophages (Mphi) to a level much higher than that in wild-type (WT) mice. The results also suggested that the NK cell is the source of IFN-gamma that is primarily responsible for this alveolar Mphi priming. To further study the roles of IL-10-inhibiting chitin-induced IFN-gamma production, we used spleen cell cultures. The experiments showed that IL-12, IL-18, and TNF-alpha, which were produced by chitin-stimulated Mphi, contributed to the IFN-gamma-inducing activity of chitin. Our results established that exogenous IL-10 inhibited chitin-induced IFN-gamma production in spleen cell cultures from both KO and WT mice. Exogenous IL-10 also inhibited IL-12 and TNF-alpha production by chitin-stimulated Mphi. Exogenous IL-10 decreased IL-12- or IL-18-induced IFN-gamma levels in KO but not in WT NK cell cultures. However, exogenous IL-10 enhanced IFN-gamma levels when NK cells were stimulated simultaneously with both IL-12 and IL-18 in KO and WT cultures. Our in vitro data indicate that IL-10 has differential effects on chitin-induced IFN-gamma production. However, the inhibitory effects of endogenous IL-10 appear to be dominant in the chitin-induced alveolar Mphi priming response in vivo.

Animals↗
PubMed1998

MPB64 mycobacterial antigen: a new skin-test reagent through patch method for rapid diagnosis of active tuberculosis.

SETTING: A collaborative study between the Japan BCG Laboratory, Tokyo, Japan, and the Infectious Disease Section, Philippine General Hospital, Manila, the Philippines. Tuberculosis patients from four clinics in the vicinity of Manila, Our Lady of Grace Parish, Sto. Niño de Tondo Parish, the Canossa Health and Social Center, and the Health Care Development Center, were examined. OBJECTIVE: To develop a new, simple and rapid diagnostic method for active tuberculosis. Subjects were tested for skin reaction to a special antigen, MPB64, by the patch test method instead of intradermal injection of purified protein derivative (PPD). DESIGN: Fifty-three active tuberculosis patients and 43 healthy PPD-positive controls were tested to determine whether or not the reaction to MPB64 was positive only in active tuberculosis patients. RESULTS: Fifty-two of the 53 active tuberculosis patients showed a positive reaction to MPB64, while none of the 43 PPD-positive controls did. The specificity of MPB64 to active tuberculosis was 100%, and the sensitivity was 98.1%. The efficacy of the test was 98.9%. CONCLUSION: The patch test with MPB64 is a promising method for the diagnosis of active tuberculosis, distinguishing tuberculous patients from those who are infected but have not developed the disease, and also from BCG-vaccinated individuals. This new skin test is a subject for further evaluation and it is important to compare the results with PPD Mantoux.

Animals↗
PubMed1998

[Analysis of Mycobacterium tuberculosis-derived substance which induces interleukin-12 production from macrophages].

Protection of hosts against tuberculosis depends on expression of cellular immunity. To express cellular immunity, interleukin 12 (IL-12) has been shown to play an important role. Although Mycobacterium tuberculosis is known to induce IL-12 from macrophages (M phi s), the mechanism for the induction is still unclear. To understand the mechanisms of IL-12 induction from M phi s by M. tuberculosis, the IL -12-inducing ability of substances derived from M. tuberculosis was investigated in vitro. Production of IL-12 in culture medium of M phi s was measured by ELISA system using specific antibodies. Live M. tuberculosis H37Rv induced slightly higher IL-12 production than live M. tuberculosis H37Ra upon stimulation of human or mouse alveolar macrophages (hAM phi s or mAM phi s). Heat-killed M. tuberculosis failed to induce IL-12 production of alveolar macrophages (AM phi). The responses of hAM phi s and mAM phi s to M. tuberculosis were remarkably different. mAM phi s produced five times larger amount of IL-12, compared with that from hAM phi s. Human peripheral blood mononuclear cells (PBMC) obtained by the density gradient centrifugation were also used for induction of IL-12 production. Although production levels of IL-12 from PBMC stimulated with M. tuberculosis were below the detectable level, addition of interferon-gamma (IFN-gamma) or neutralizing antibody against IL-10 augmented the production of IL-12 from PBMC, suggesting that IFN-gamma and IL-10 regulate the production of IL-12 from M phi positively and negatively, respectively. To characterize the physicochemical properties of IL-12-inducing molecules, M. tuberculosis H37Rv was disrupted by pressing with 1,000 bar and centrifuged and separated into cytosol and cell wall fraction. The culture filtrate was also examined on IL-12-inducing activity. Among the three subjects examined, cytosol was found to induce the highest production of IL-12 from mAM phi s 1 day after the stimulation. Addition of IFN-gamma to the cytosol fraction markedly increased the production of IL-12 from mAM phi s. The molecular weight of IL-12-inducing substance was shown to be more than 30kDa by fractionating with molecular filters. Treatment of 30kDa-fraction with IL-12-inducing activity by proteinase K completely abolished the activity. Furthermore, approximately 90% of IL-12-inducing activity of 30kDa-fraction was lost by proteinase K treatment even in the presence of IFN-gamma. These results indicate that the major component of IL-12-inducing activity is a protein. The identification of this IL-12-inducing active substance may provide a new therapeutic tool for tuberculosis.

Animals↗
PubMed1997

Mortality experience of Navajos with type 2 diabetes mellitus.

OBJECTIVES: We sought to determine the contribution of type 2 diabetes mellitus to mortality in a Navajo population, and to assess the impact of pre-existing coronary heart disease on this relationship. METHODS: A cohort of 77 Navajos with type 2 diabetes mellitus and 77 non-diabetic controls matched on age, gender and community of residence were followed for an 18-year period, from 1974 to 1992. RESULTS: The vital status of 152 of the 154 study subjects was ascertained at 18-year follow-up. There were 30 deaths (39%) in the type 2 diabetes group and 13 (17%) in the control group during the 18-year period which was significantly different in bivariate matched pairs analysis (risk ratio = 3.12, McNemar's chi 2 = 7.76, p < 0.01). Multivariate conditional logistic response models (risk ratio = 3.02, 95% CI 1.21, 7.53) and stratification analysis (McNemar's Summary chi 2 = 8.05, 2 df, p < 0.05), confirmed that survival was significantly different for the two groups, even when controlling for baseline cardiovascular comorbidity and hypertension. CONCLUSION: These data describe the mortality impact of the epidemic of type 2 diabetes and cardiovascular disease now accelerating among the Navajo. The significant mortality differences between the diabetes and non-diabetes groups and the continuing rise in prevalence of type 2 diabetes underscore the need for an effective community-based approach to diabetes prevention among the Navajo.

Arizona↗
PubMed1997

Current concepts and advances in clinical laboratory testing for autoimmune diseases.

This review discusses the current concepts of immunological tolerance, physiological vs. pathological autoimmunity, autoimmune diseases, and laboratory tests helpful in diagnosis. The autoantibodies in organ-specific autoimmune diseases are directed against antigens of the injured organs, whereas the antinuclear antibodies (ANA) detected in systemic autoimmune diseases are detected against a vast array of nuclear and intracellular antigens and peptides necessary for DNA/RNA synthesis, repair, splicing, and transcription. Knowledge of the mean titer and presence or absence of specific ANA types will help predict the nature of the disease and the response to therapy. Noteworthy features of these "ANA profiles" are (1) patients with systemic lupus erythematosus frequently have multiple types of ANA but anti-dsDNA and anti-SM are diagnostic, (2) patients with drug-induced lupus have ANA restricted to antihistone, (3) patients with mixed connective tissue disease have ANA restricted to anti-RNP, (4) patients with CREST (calcinosis, Raynaud's, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome have ANA restricted to anticentromere, (5) ANA with anti-SS-A/Ro specificity is associated with vasculitis and nephritis, (6) ANA with anti-SS-B/La and anti-nRNP specificities is associated with milder clinical disease, (7) ANAs with anti-Jo-1 and PM-Scl specificities are associated with pulmonary fibrosis and poor prognosis. Technological advances in the fields of molecular immunogenetics are guiding the studies of autoimmune diseases from serological and histopathological evaluations toward search for subcellular risk factors such as chemical and biological agents and susceptibility genes. Knowledge of these factors will help (1) to identify disease susceptibility genes prior to clinical onset and irreversible tissue damage, (2) to avoid environmental risk factors, and (3) to devise specific immunosuppressive strategies.

Autoimmune Diseases↗
PubMed1997

Role of autoantibody tests in the diagnostic evaluation of neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) can be defined as a significant and unequivocal change in the baseline neurologic and psychiatric function identified by history and physical examination. NPSLE can involve the central nervous system and/or the peripheral autonomic nervous system. This article reviews the clinical manifestations, pathology, and immunopathogenesis of NPSLE. The use and importance of diagnostic procedures including autoantibody assays in the evaluation of NPSLE are discussed.

Autoantibodies↗
PubMed1996

Extracellular matrix and integrin composition of the normal bladder wall.

We performed an immunohistochemistry study of the normal human bladder so as to understand the interactions of extracellular matrix (ECM) components and the integrins of cell adhesion that accommodate the volume changes and maintain an impermeable barrier to reabsorption of urine in the bladder. The normal human urothelial cell and/or its plasma membrane contained integrins alpha 3, alpha V, beta 1, and beta 4 but did not contain integrin beta 3. The urothelial basement membrane (UBM) contained collagen type IV and laminin. Fibronectin and integrins alpha 3 and beta 4 were found in or near the UBM area, with types I and III collagen and tenascin abutting the area. The patterns of collagen, laminin, tenascin, vitronectin, fobronectin, and the alpha 3, alpha V, beta 1, and beta 3 integrins in the lamina propria, vessels, nerves, and smooth-muscle layers are described. These findings detail the normal anatomical ECM/integrin relationship that provides the cellular basis for bladder-wall relationships responsible for its impermeable state and other functions.

Cells, Cultured↗
PubMed1996

Effective isolation of MPB64 from a large volume of culture filtrate of Mycobacterium bovis BCG Tokyo.

MPB64, a secretory protein of Mycobacterium bovis BCG Tokyo, was isolated from a culture filtrate of the bacteria in Sauton synthetic medium harvested on day 8. The protein was isolated by five steps; (i) concentration of the culture filtrate by cutting the molecules smaller than 5 kDa with the Millipore Pellicon Cassette system, (ii) affinity separation by a Phenyl Sepharose CL-4B column, (iii) separation with a DEAE-Sepharose CL-6B column with 3 M urea, (iv) separation with a Sephacryl S200HR column, and (v) separation with a DEAE-Sepharose column without urea. MPB64 in each fraction was determined by comparing the band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with that of standard MPB64. The specificity of isolated MPB64 was tested by immunoblotting with anti-MPB64 antibody. The potency of isolated MPB64 in eliciting skin reaction in the BCG-sensitized guinea pigs was the same to that of standard MPB64. The method described herein is an improved one for isolating MPB64 from a large volume of culture filtrate of M. bovis BCG Tokyo. The technique should be applicable to isolation of other mycobacterial secretory proteins.

Antigens, Bacterial↗