Lymphoid microstructures in rheumatoid synovitis.
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Arthritis, Rheumatoid↗
Biomedical subjects
S Takemura
Publications and source records attributed to S Takemura.
Relation between smoking prevalence and various social factors in Japan.
Although the smoking prevalence among women is significantly low compared to that among men in Japan, the prevalence in young Japanese women has been steadily increasing recently. The relationship between the prevalence of smoking among the general population and various social factors was investigated with a special emphasis regarding the influence of household size on the smoking prevalence of young Japanese women. Thirty-one thousand and six hundreds twenty-seven subjects of 20 years and older were randomly selected from the general population of Japan. The Ministry of Health and Welfare, Japan planned and conducted the survey. Subjects were divided into male and female, and smoking prevalence was investigated in terms of age, place of residence, occupation and household size factors. Statistical analyses were performed using chi-square test and multiple logistic regression. Multiple logistic regression analyses suggested that for men there was a strong relationship between becoming a smoker and living in a municipality with a smaller population, and that for women who were living in a municipality with a larger population. For women, as the size of a household increased from living alone to a two- or three-generation household, the tendency to becoming a smoker decreased, but this tendency was not observed among men. As to reasons for quitting smoking, more women than men living in two- and three-generation households gave "family's advice" as a major reason (p < 0.01). The steady replacement of the traditional three-generation household by smaller households in Japan may lead to an increase in the number of young women who smoke.
Adult↗
[Study of factors that influence the use of ambulances in Japanese prefectures].
PURPOSE: The objective of this study was to clarify the factors that influence the rate of patient-carriage by ambulances in Japanese Prefectures. METHOD: The study was conducted using data on cases of patients with mild conditions carried by ambulances in Japanese prefectures in 1993, concentrating the factors that influence the rate of usage. The cases were analyzed focusing on three major types of medical emergencies (accounting for 93.4% of the total): sudden illnesses, traffic accidents and general injuries. SPSS for Windows was used for statistical analysis. RESULTS AND DISCUSSION: Data analysis by age group and type of medical emergency showed a positive correlation (r > 0.7) for the rate of cases with mild conditions carried by ambulances in all age groups (early childhood, adolescence, adult and senior) and the three major types of medical emergencies. Particularly, a strong correlation (r > 0.9) was observed with regard to patients suffering from sudden illnesses and general injuries. Multiple regression analysis showed that the rate for patients with mild cases carried by ambulances was higher in prefectures where; (1) there were more cases of administrative litigation related to individuals' rights, and (2) there were many nuclear families that tended to lack the capacity for family care. In addition, it also became evident that the rate for patients with mild injuries from traffic accidents was higher in prefectures where; (1) the rate for male-driver license holders for small- and medium-size cars was higher, and (2) the ratio of numbers of vehicles to total roadway area was higher. CONCLUSIONS: The findings suggest that factors unrelated to medical emergencies have a major influence on use of ambulance. Reevaluation of policy in order to promote appropriate utilization is necessary.
Accidents, Traffic↗
[The validity of repeated mail surveys concerning smoking habits for Japanese physicians].
PURPOSE: A cross-sectional study of smoking prevalence among medical doctors was performed using questionnaires. Mailing four times proved essential in order to obtain a reasonable number of responses from the subjects. The objective of the present study was to analyze the smoking characteristics of the subjects who returned the questionnaires after the second to fourth mailings. METHODS: A set of an anonymous questionnaire and a letter from the President of the Japan Medical Association (JMA) requesting cooperation was mailed with a return envelope with the subject's name and address written to 3,000 male and 1,500 female doctors randomly selected from the roster membership of the JMA. The survey was conducted between February and June 2000. RESULTS: The collection rate after the first mailing was 66%, while the subtotal collection rate for the second through fourth mailings was 21%, bringing the grand-total to 87%. The total prevalence of smoking among the subjects who had sent back the questionnaire on the second to fourth mailings was approximately 1.5 times higher than for those who had sent back the questionnaire after the initial mailing for both male and female subjects. As to other characteristics of the subjects who only responded after the second to fourth mailings were: working in hospitals (odds ratios; male: 1.39, female: 1.47), not giving smoking cessation guidance (odds ratio; male: 0.58), and not recognizing the idea that doctors should not smoke (odds ratio; female: 0.67). CONCLUSIONS: The results suggested that for future surveys on smoking to be conducted in academic institutions or work-places, efforts to obtain responses from those who do not answer the first attempt should take into consideration these points.
Adult↗
[The influence of lifestyle and night-shift work on sleep problems among female hospital nurses in Japan].
STUDY OBJECTIVE: In this study, by conducting a questionnaire survey, we aimed to clarify the situation regarding sleep disorders in female hospital nurses and their relation with night-shift work and lifestyle. METHODS: The subjects were female nurses working at 5 hospitals, each with more than 400 beds. The survey was carried out in July 2000. The questionnaire contained six items concerning sleep quality from the Pittsburgh Sleep Quality Index (PSQI), two new items on sleep drafted by ourselves, and some questions on lifestyle and shift-work status. RESULTS: Among all female nurses, statistically significant differences were observed between those working and those not working night shifts for 7 items regarding sleep (P < 0.05). Significant correlations were observed between sleep disorders and the following factors: (1) working night shift, (2) having anxiety or stress, (3) getting less than 6 hours of sleep, (4) working in cities, (5) having children, and (6) bathing more than 1 hour before going to bed. In addition, significant correlations were observed between getting less than 6 hours of sleep and the following factors: (1) being 40 years of age or older, (2) working in cities, and (3) having anxiety or stress. CONCLUSIONS: The results of this study suggest that sleep problems among nurses are associated not only with night-shift work but also with lifestyle. They also suggest that nurses who work night shifts, especially in Tokyo, should try to get sufficient hours of sleep to ensure good quality of sleep.
Adult↗
New thiocholine ester substrates for the assay of human serum cholinesterase.
BACKGROUND: Several thiocholine alkanoyl esters were newly synthesized and explored as substrates for the assay of human serum cholinesterase after being subjected to the Ellman reaction (Arch Biochem Biophys 1958;74:443-50 and Arch Biochem Biophys 1959;82:70-7). METHODS: We synthesized thiocholine ester iodides by the method of Renshow et al. (J Am Chem Soc 1938;60:1765-70). We examined solubility in H(2)O, substrate specificity serum for cholinesterase, (spontaneous) self-hydrolysis, storage stability, and reaction conditions for measurement of the activity of the enzyme. RESULTS: Isobutyryl and cyclohexane-carboxyl esters showed the best efficiency for the specific and stable assay of human serum cholinesterase. Aqueous solubility of each was >10 mmol/L, and the reactivity with acetylcholinesterase was negligible. For isobutyryl and cyclohexane-carboxyl esters, respectively, spontaneous hydrolysis in the aqueous phase was approximately 1/25 and approximately 1/175 slower than the enzymatic hydrolysis, and assays with these substrates were linear to 1800 and 3000 U/L, respectively. The K(m) values of these acylthiocholines with human cholinesterase were almost equivalent (6.9 x 10(-3) mmol/L). The substrates were stable in aqueous solution and in the solid state as the iodides for at least 5 years at 5 degrees C. CONCLUSIONS: The isobutyrate and cyclohexane-carboxylate of thiocholine are suitable for the specific assay of human serum cholinesterase.
Cholinesterases↗
[Implementation and evaluation of public relations activity in a community health program].
OBJECTIVE: This study evaluated public relations activity in a community health program in order to develop effective strategies to attract the public attention for the program. METHODS: An intervention study was conducted on public relations for "Nutrition Seminar for Citizens," sponsored by the Health Department of Machida City, Tokyo, in October, 1999. One ward in the city was selected as an intervention area, and another ward which had similar demographic and geographic characteristics was chosen as a control area. Two target populations were defined; one was women in their 20s to 60s (#1) and the other was those who had previously never utilized community health programs sponsored by the city (#2). Handbills were used as the medium for public relations for the seminar. These announced the time, place and content of the nutrition seminar and were designed by authors with special attention to catchphrases, colors and fonts. Handbills were distributed in the intervention area through elementary schools, local voluntary organizations and local health volunteers. In addition, the authors directly handed them out to people in front of two supermarkets in the town. The sources of seminar information were requested from the participants of the Nutrition Seminar with a self-administered questionnaire. RESULTS: 1. The percentage of participants who received the seminar information from handbills was higher than that of those who used monthly newsletters from the city as a source of information. 2. The percentage of participants from the intervention area was higher than that from the control area. 3. Regarding target populations #1 and #2, there were no differences in participation rates between the intervention and control area. 4. Among the four distribution routes, the local voluntary organization route was the most effective for attracting participants. CONCLUSIONS: The results show that handbills can be an effective medium for pubic relations to increase the number of participants in community health programs. Also, local voluntary organizations can play a crucial role in information transfer in the community because of their high credibility. On the other hand, we could not reach specified target populations with the medium. Further surveys are needed to establish optimal media and routes to reach appropriate target populations in health programs.
Adult↗
[Clinical significance of interferon therapy in treatments for hepatitis C virus-related hepatocellular carcinoma].
The results of liver resection for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) are affected by persistent active hepatitis and/or hepatic fibrosis including cirrhosis. In patients infected with HCV, interferon therapy prevents the development of HCC by eradication of HCV and/or the remission of active hepatitis. Although HCCs are found even in some patients treated with interferon, the results of liver resection for such HCCs were satisfactory, especially in patients successfully treated with interferon. Postoperative interferon-alpha therapy decreased recurrence after resection of HCV-related HCC in a randomized controlled trial. Strategies for viral infection as well as the carcinoma can improve the outcome after treatment of HCV-related HCC. Interferon therapy is useful to improve the outcome after treatments for HCV-related HCC.
Antineoplastic Agents↗
Large focal nodular hyperplasia of the liver: possible to evade surgical resection.
PURPOSE: Although recent advances in diagnostic imaging have allowed a number of patients with focal nodular hyperplasia (FNH) to avoid surgical treatment, the natural course of large FNH is still unknown. CASE REPORT: A 25-year-old man was admitted because of a large hepatic mass detected on routine examination in June 1998. The only laboratory abnormality was an elevated gamma-GTP. Computed tomography, angiography, positron emission tomography using F-18 fluorodeoxyglucose (FDG-PET), and scintigraphy using technetium-99m-galactosylneoglycoalbumin(99mTc-NGA) demonstrated a spoke-wheel appearance of vessels, normal hepatocytes, and no malignancy. Histologic findings on needle biopsy were consistent with FNH. After informed consent, the patient agreed to observation. Two years after the initial diagnosis, he has no symptoms, and there are no changes in the size or character of the lesion on computed tomography. DISCUSSION: Careful observation of patients with FNH is required because its natural course is unknown and these lesions can bleed or rupture.
Adult↗
Cell-cell interactions in synovitis. Interactions between T cells and B cells in rheumatoid arthritis.
In rheumatoid arthritis, T cells and B cells participate in the immune responses evolving in the synovial lesions. Interaction between T cells and B cells is probably antigen specific because complex microstructures typical of secondary lymphoid organs are generated. Differences between patients in forming follicles with germinal centers, T-cell-B-cell aggregates without germinal center reactions, or loosely organized T-cell-B-cell infiltrates might reflect the presence of different antigens or a heterogeneity in host response patterns to immune injury. Tertiary lymphoid microstructures in the rheumatoid lesions can enhance the sensitivity of antigen recognition, optimize the collaboration of immunoregulatory and effector cells, and support the interaction between the tissue site and the aberrant immune response. The molecular basis of lymphoid organogenesis studied in gene-targeted mice will provide clues to why the synovium is a preferred site for tertiary lymphoid tissue. B cells have a critical role in lymphoid organogenesis. Their contribution to synovial inflammation extends beyond antibody secretion and includes the activation and regulation of effector T cells.
Animals↗
Functional Fv fragment of an antibody specific for CD28: Fv-mediated co-stimulation of T cells.
The most predominant co-stimulation pathway, which is critical for T cell activation and proliferation, is the CD28-B7 pathway. The anti-CD28 monoclonal antibody (mAb) also provides a co-stimulatory signal to T cells. In order to construct a functional Fv fragment (complex of VH and VL domains) of anti-CD28 antibody using a bacterial expression system, cDNA encoding the variable regions of immunoglobulin from 15E8 hybridoma cells was cloned and expressed in Escherichia coli. The Fv fragment was obtained as a soluble protein from the periplasmic fraction and showed a binding pattern similar to parental IgG. The Fv fragment induced proliferation of peripheral blood mononuclear cells in the presence of anti-CD3 or anti-CD2 mAb and enhanced anti-tumor activity of anti-MUC1x(anti)-CD3 bispecific antibody when tested with lymphokine-activated killer cells with T cell phenotype. Thus, the anti-CD28 Fv fragment will be promising not only for the study of co-stimulation, but also for cancer immunotherapy.
Amino Acid Sequence↗
The thoracoscopic approach for internal mammary nodes in breast cancer.
BACKGROUND: This pilot study was conducted to estimate the use of the thoracoscopic surgery as a new approach for the internal mammary nodes (IMN) in breast cancer. PATIENTS AND METHODS: For this study, 21 women with breast cancer who underwent the approach for nodes IMN were enrolled. All the women had suspicious IMN metastasis and no distant metastasis. RESULTS: Thoracoscopic IMN dissection was performed safely for 20 of the women, with an average operative time of 44 min. One woman was excluded from the procedure because of pleural adhesion. The patients were restricted from walking for 1.3 days because of chest drainage, but no patients had severe complication or chest wall deformity after the operation. Six patients had positive IMN outcomes. After surgery, 10 of the 20 patients had a lower tumor node metastases (TNM) staging. Two patients who tested positive for IMN and three who tested negative experienced a relapse, but none had pleural dissemination in a median follow-up period of 24 months. CONCLUSION: Thoracoscopic surgery may be useful in managing patients with IMN.
Adult↗
Post-ischemic intraportal adenosine administration protects against reperfusion injury of canine liver.
Although adenosine has been postulated to inhibit ischemia-reperfusion injury in various tissues, its in vivo cytoprotective mechanism is not fully known. The aim of this study was to determine the effect of intraportally infused adenosine on reperfusion injury in the canine liver. Two h ischemia and reperfusion of the liver were induced in beagle dogs by clamping the portal triad. Either adenosine or saline was infused in the portal vein after reperfusion for 60 min. Levels of serum aspartate aminotransferase and alanine aminotransferase and the survival of animals were examined. Hepatic levels of protein carbonyls and glutathione were also measured, as markers of oxidative stress. One h after reperfusion, the liver was perfused with nitroblue tetrazolium and the formation of formazan was observed to evaluate superoxide formation. Twenty-four h after reperfusion, 100% of animals in the adenosine group and 33% of animals in the control group survived. Adenosine significantly decreased the reperfusion-induced increase in serum levels of aspartate aminotransferase and alanine aminotransferase. Adenosine also suppressed the formation of protein carbonyls and the decrease in glutathione levels. Histologically, neutrophil infiltration, superoxide formation, and apoptosis were decreased by adenosine. These results suggest that intraportally infused adenosine attenuates reperfusion injury of the liver, presumably by suppressing the activation of neutrophils and oxidative stress.
Adenosine↗
Isolation and chemical--structural identification of a novel aromatic amine mutagen in an ozonized solution of m-phenylenediamine.
The mutagenicity of a m-phenylenediamine (m-PD) solution was markedly enhanced by oxidation with ozone. The ethyl acetate extracts from a m-PD solution ozonized at pH 10.7 were fractionated by normal-phase and reversed-phase column chromatography to isolate mutagens by monitoring mutagenic activities on Salmonella typhimurium TA98 in the presence of a mammalian metabolic activation system (S9 mix). From fraction 5-3-2, which exhibited the strongest mutagenicity (308000 revertants/mg), a major mutagenic compound was isolated. On the basis of the high-resolution EI-mass, (1)H NMR and (13)C NMR spectral, and X-ray crystallography data, the structure of this compound was determined to be 2-amino-5-[(3-aminophenyl)amino]-4-[(3-aminophenyl)imino]-2, 5-cyclohexadien-1-one (PDT-1), which is a novel compound. PDT-1 is a newly identified frame-shift type mutagen, inducing 65400 revertants and 295000 revertants of S. typhimurium TA98 and YG1024 per micromole, respectively, in the presence of S9 mix. When a m-PD solution was oxidized with 1 or 2 mol of ozone at pH 4.0, 7.0, and 10.7, the contribution of PDT-1 to the mutagenicity of ethyl acetate extracts from the ozonized m-PD solution was 5-23%.
Animals↗
Functional construction of the anti-mucin core protein (MUC1) antibody MUSE11 variable regions in a bacterial expression system.
A bacterial expression system for the variable region fragments (Fvs) of the anti-MUC1 tumor antigen antibody MUSE11 has been constructed. The Fv fragment showed binding specificity toward TFK-1 cells, with slightly reduced affinity compared to its parent IgG. The single-chain Fv fragment was arranged in two orders, VH-linker-VL and VL-linker-VH. However, linking the regions with a flexible peptide linker (GGGGS)(3) or with a shorter linker (GGGGS) led to a dramatic decrease in the biological activity toward the target antigen in both arrangements, suggesting that the MUSE11 antibody loses its activity when the domains are linked with polypeptide linkers. These results indicate that the variable region domains of the anti-MUC1 antibody MUSE11 have specificity only in the Fv form, and that linking the domains strongly reduces the association with its target antigen. Gel filtration analysis indicates that the scFv has a dimeric structure, suggesting that the inactivation of MUSE11 scFv is due to unfavorable intermolecular associations of the scFv chains. To our knowledge, this is the first report of a significant reduction in affinity caused by linking the variable domains in both arrangements, i.e., VH-VL and VL-VH.
Animals↗
Construction of a diabody (small recombinant bispecific antibody) using a refolding system.
Diabodies are the recombinant bispecific antibodies (BsAbs), constructed from heterogeneous single-chain antibodies. Usually, diabodies have been prepared from bacterial periplasmic fraction using a co-expression vector (i.e. genes encoding two chains were tandemly located under the same promoter). Some diabodies, however, cannot be expressed as a soluble material owing to inclusion body formation, which limits the utilization of diabodies in various fields. Here we report an improved method for the construction of diabodies using a refolding system. As a model, a bispecific diabody binding to adenocarcinoma-associated antigen MUC1 and to CD3 on T cells was studied. One chain consisted of a VH specific for MUC1 linked to a VL specific for CD3 with a short polypeptide linker (GGGGS). The second was composed of a VL specific for MUC1 linked to a VH specific for CD3. The two hetero scFvs were independently obtained from intracellular insoluble fractions of Escherichia coli, purified, mixed stoichiometrically (at an equivalent molar ratio of 1:1) and refolded. The refolded two hetero scFv has a hetero-dimeric structure, with complete specificity for both target cells [i.e. MUC1 positive cells and CD3 positive lymphokine-activated killer cells with a T cell phenotype (T-LAK)]. Evaluation of the in vitro efficacy of T-LAK with the diabody by growth inhibition assay of cancer cells demonstrated maximum growth inhibition of cancer cells to reach approximately 98% at an effector:target ratio (E:T ratio) of 10, almost identical with that with anti-MUC1xanti-CD3 chemically synthesized BsAbs (c-BsAbs). This is the first report of the construction of a diabody using a refolding system.
Antibodies, Bispecific↗
Pharmacokinetics and in vivo gene transfer of plasmid DNA complexed with mannosylated poly(L-lysine) in mice.
To achieve mannose receptor-mediated, cell-specific, in vivo gene transfer by intravenous injection of plasmid DNA, mannosylated poly(L-lysine) (Man-PLL) was synthesized as a carrier molecule, and mixed with a plasmid DNA encoding chloramphenicol acetyltransferase (CAT) gene to form DNA/Man-PLL complex. The particle size and zeta potential of DNA/Man-PLL (prepared at 1:0.7 on a weight basis) were determined to be 220 nm and +12 mV, respectively. The pharmacokinetics of the DNA/Man-PLL complex was assessed in mice using 32P-labeled DNA ([32P]DNA). After intravenous injection of [32P]DNA/Man-PLL, the radioactivity in plasma fell rapidly and was recovered mainly in the liver nonparenchymal cells. The amount in the liver reached more than 80% of the dose. Radioactivity observed in kidney, lung, and spleen was very low compared to that in the liver. Then, the in vivo gene expression after intravenous injection of DNA/Man-PLL was examined by a CAT assay. Highest CAT activity was detected in the liver, but no activity was detected in the lung, kidney, and spleen. These results clearly indicate that a cell-specific gene delivery system can be developed by regulating the biodistribution of DNA/carrier complex through the control of its physicochemical properties.
Animals↗
[CD16+ CD56- indolent, NK cell-lineage granular lymphocyte proliferative disorder with autoimmune hemolytic anemia].
A 64-year-old man was given a diagnosis of CD16+ CD56- natural killer cell-lineage granular lymphocyte proliferative disorder (NK-GLPD) with Coombs-negative autoimmune hemolytic anemia (AIHA). Two courses of 1,000 mg intravenous methylprednisolone for 3 days were transiently effective for both AIHA and NK-GLPD. On the recurrence of AIHA, NK-GLPD also re-appeared. The same treatment was effective in controlling both diseases again. This was a rare case of NK-GLPD combined with autoimmune disease.
Anemia, Hemolytic, Autoimmune↗