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1.
Br J Dermatol ; 182(2): 364-372, 2020 02.
Article in English | MEDLINE | ID: mdl-31077338

ABSTRACT

BACKGROUND: The normal stratum corneum (SC) has an upper basket-weave (BW) pattern layer and a lower compact layer. The transition from compact to BW SC is well associated with a transition from diffuse to peripheral distributions of corneodesmosomes (CDs). The loss of transition from compact SC to BW SC appears to cause structural and barrier-function impairments. OBJECTIVES: To show the involvement of the BW SC in maintaining the physiological properties of the skin. METHODS: Reconstructed human epidermis (RHE) with a complete BW structure was created by treatment with prepared emulsion-A, an oil-in-water emulsion. The RHE tissues were subjected to histological analysis, and the distribution of CDs on the SC with or without BW SC was analysed by anti-desmoglein (Dsg)1 antibody immunofluorescence and ultrastructural and Western blotting analyses. Ultrastructural analysis of intercellular lipids was performed. The mechanical properties of the RHE were evaluated. RESULTS: Emulsion-A successfully generated the BW SC in the RHE in which the degradation of CDs was promoted. The intercellular space of the BW SC generated by emulsion-A was filled with multilamellar lipid sheets. The softness of the SC with a BW structure formed with emulsion-A was higher than that of the compact SC in RHE. The outermost SC Dsg1 degradation (formation of the BW SC as determined with Dsg1 pixels) was correlated with water-barrier functions and the SC softness of healthy human cheek, which varied widely. CONCLUSIONS: Emulsion-A successfully generated the BW SC in RHE for the first time. This method is suggested to be a useful tool for investigating the physiological significance of the BW SC in vitro. Determination of Dsg1 content in the SC obtained by tape stripping from human skin allows study of the effects of external stimulants, such as creams and ointments, including cosmetics, on the completeness of the BW SC in situ without biopsy. What's already known about this topic? The normal stratum corneum (SC) has two layers, an upper basket-weave (BW) pattern layer and a lower compact layer. Epidermal diseases such as ichthyosis vulgaris and X-linked ichthyosis have an incomplete or no BW SC and impaired SC barrier functions, in which corneodesmosome (CD) degradation in a peripheral distribution is impaired. The roles of the BW SC in the physiological properties of human skin have not been clearly elucidated. What does this study add? Reconstructed human epidermis (RHE) with a complete BW structure was generated for the first time by treatment with oil-in-water emulsion-A. The formation of the BW SC was associated with a decrease in Dsg1 content, which represents the CD number in the SC. The intercellular space of the BW SC generated by emulsion-A, but not compact SC, was filled with multilamellar lipid sheets. The softness of the SC with a BW structure formed by emulsion-A treatment was higher than that of the compact SC in RHE. What is the translational message? RHE with a complete BW SC generated by emulsion-A treatment is suggested to be a useful tool for investigating effects on the physiological functions of the BW SC, as in treatments with creams and ointments including cosmetics. Determination of desmoglein 1 content in the SC obtained by tape stripping from human skin can make it possible to study the effects of external stimulants, such as creams and ointments, including cosmetics, on the completeness of the BW SC in situ without biopsy.


Subject(s)
Epidermal Cells , Epidermis , Skin Physiological Phenomena , Water Loss, Insensible , Administration, Topical , Cheek , Epidermis/metabolism , Humans , Skin
2.
J Nat Med ; 71(1): 265-271, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27848205

ABSTRACT

Glycyrrhiza uralensis roots used in this study were produced using novel cultivation systems, including artificial hydroponics and artificial hydroponic-field hybrid cultivation. The equivalency between G. uralensis root extracts produced by hydroponics and/or hybrid cultivation and a commercial Glycyrrhiza crude drug were evaluated for both safety and efficacy, and there were no significant differences in terms of mutagenicity on the Ames tests. The levels of cadmium and mercury in both hydroponic roots and crude drugs were less than the limit of quantitation. Arsenic levels were lower in all hydroponic roots than in the crude drug, whereas mean lead levels in the crude drug were not significantly different from those in the hydroponically cultivated G. uralensis roots. Both hydroponic and hybrid-cultivated root extracts showed antiallergic activities against contact hypersensitivity that were similar to those of the crude drug extracts. These study results suggest that hydroponic and hybrid-cultivated roots are equivalent in safety and efficacy to those of commercial crude drugs. Further studies are necessary before the roots are applicable as replacements for the currently available commercial crude drugs produced from wild plant resources.


Subject(s)
Drugs, Chinese Herbal/chemistry , Glycyrrhiza uralensis/chemistry , Hydroponics/methods , Plant Roots/chemistry
3.
Diagn Interv Imaging ; 97(6): 611-5, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27053174

ABSTRACT

OBJECTIVE: Preoperative sentinel lymph node (SLN) mapping by lymphoscintigraphy is helpful to evaluate extra-axillary SLNs over a wider range than the blue dye method. However, the clinical value of extra-axillary SLNs remains uncertain. The goal of this study was to determine the prevalence and clinical significance of supra- or infraclavicular drainage on preoperative lymphoscintigraphy in women with breast cancer. MATERIALS AND METHODS: We retrospectively reviewed the files of 942 consecutive breast cancer women who underwent preoperative lymphoscintigraphy for SLN biopsy at our institution between April 2004 and March 2015. RESULTS: Supra- or infraclavicular drainage was detected in 5/942 women (0.5%) on preoperative lymphoscintigraphy. An axillary hot spot was detected in all five women, and a positive axillary SLN was detected in four women. Breast tumor locations were the upper inner or outer quadrants in four women and the lower outer quadrant in one woman. The median follow-up period was 75 months (mean: 92; range: 26-111 months). Recurrence outside the axilla was found in three (60%) women. The woman with a negative SLN status did not undergo adjuvant chemotherapy, but developed extra-axillary lymph node recurrence 3 years after primary surgery. No patient died of metastatic breast cancer at the last follow-up. CONCLUSIONS: The detection of the supra- or infraclavicular SLNs on lymphoscintigraphy may provide additional staging information to tailor individual treatment regimens with regard to the potential risk of recurrence or metastasis of breast cancer.


Subject(s)
Breast Neoplasms/pathology , Lymph Nodes/diagnostic imaging , Lymphoscintigraphy , Adult , Aged , Axilla , Carcinoma, Ductal, Breast/pathology , Female , Humans , Lymphatic Metastasis , Middle Aged , Preoperative Care , Prevalence , Retrospective Studies , Sentinel Lymph Node Biopsy
5.
Diagn Interv Imaging ; 97(1): 65-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25846685

ABSTRACT

OBJECTIVE: A retrospective assessment of differences in congenital cholesteatoma CT findings with a focus on type of cholesteatoma mass. MATERIALS AND METHODS: The medical records and CT images of 14 patients with congenital cholesteatomas in the middle ear who underwent surgery at our institution between January 2009 and July 2014 were reviewed. Cholesteatomas were classified as closed type, open type, or mixed type based on intraoperative findings. The CT findings including cholesteatoma size, location, and shape were retrospectively reviewed. RESULTS: Eight patients had closed type cholesteatomas, four had mixed type, and two had open type. The mean size of all cholesteatomas was 5.1mm. None of the cholesteatoma types indicated a tendency towards a certain location. The round shape was observed more frequently in closed type cholesteatomas than in other types (closed: 5/8; mixed: 1/4; open: 0/2). Two large closed type cholseteatomas and two mixed type cholesteatomas exhibited a constricted shape. Both of the open type cholesteatomas displayed an irregular shape. CONCLUSION: Small closed type congenital cholesteatomas were typically observed as round shaped lesions, but large closed type cholesteatomas and other type cholesteatomas tended to display shapes other than round.


Subject(s)
Cholesteatoma, Middle Ear/congenital , Cholesteatoma, Middle Ear/diagnostic imaging , Tomography, X-Ray Computed , Child , Child, Preschool , Cholesteatoma, Middle Ear/classification , Cholesteatoma, Middle Ear/pathology , Female , Humans , Infant , Male , Retrospective Studies
6.
Int J Occup Environ Med ; 5(1): 24-31, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24463798

ABSTRACT

BACKGROUND: In recent years, dentists have more opportunity of treating patients infected with blood-borne pathogens. Although compliance with infection control practice (ICP) in dental practice is required, it is not still sufficiently spread in Japan. OBJECTIVE: To identify factors associated with compliance with ICPs in the population of Japanese dentists. METHODS: In a questionnaire-based cross-sectional study in 2009, 2134 dentists in Aichi prefecture, Japan, were surveyed. They were asked for their demographic characteristics, willingness to treat HIV/AIDS patients, and knowledge about universal/standard precautions and ICP. RESULTS: Many ICP items had significant association with age, specialty for oral surgery, number of patients treated per day, willingness to treat HIV/AIDS patients and knowledge about the universal/standard precautions. In logistic regression model, knowledge about the precautions had significant associations with all ICP items. Among participants with disadvantageous characteristic group for ICP (ie, age ≥50 years, being general dentist, and treating ≤35 patients/day), knowledge about the universal/standard precautions had greater impact on exchanging handpiece for each patient and installing extra-oral vacuum in those with age of ≥50 years than in those who visited ≤35 patient per day. CONCLUSION: Knowledge about the meaning of universal/standard precautions is the most significant predictor of compliance with ICPs among Japanese dentists.


Subject(s)
Dentists/psychology , Dentists/statistics & numerical data , Guideline Adherence/statistics & numerical data , Infection Control/statistics & numerical data , Attitude of Health Personnel , Cross-Sectional Studies , Female , Humans , Japan/epidemiology , Male , Middle Aged , Surveys and Questionnaires
7.
Infection ; 40(6): 661-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22956473

ABSTRACT

BACKGROUND: Though various clinical conditions of aspergillosis can occur, depending essentially on the host's immunological status, the focus of research in North American and European countries has mainly been on invasive pulmonary aspergillosis in immunocompromised patients. There are, however, also many problems to overcome in chronic forms of aspergillosis. One of those problems is that there are no codified treatment guidelines for chronic pulmonary aspergillosis (CPA). Especially in Japan, this issue is more serious, because there are more cases with CPA due to the many aged people with past history of tuberculosis. Several clinical cases and case series have reported the usefulness of the various antifungal agents that are available. The new triazole, voriconazole, in particular, seems to be effective in the treatment of CPA. The aim of the present study is to evaluate the efficacy and safety of voriconazole in the treatment of CPA in non-immunocompromised patients. PATIENTS AND METHODS: We conducted a prospective, open-label, non-comparative, multicenter study over a 2-year period. For inclusion in the study, patients with confirmed or probable CPA were recruited in 11 hospitals of the National Hospital Organization in Japan. Clinical, radiological, serological, and mycological data were collected at baseline and 12 weeks after treatment or at the end of treatment. RESULTS: Among 77 patients enrolled in the study, 71 patients (mean age 65.9 years, 56 males and 15 females) were eligible for the study. All of the eligible patients presented with underlying lung diseases, including sequelae of tuberculosis (n = 35), non-tuberculous mycobacterial lung disease (n = 8), chronic obstructive pulmonary disease (COPD) (n = 8), interstitial pneumonia (n = 7), cystic lung disease (n = 4), pneumothorax (n = 3), bronchial cancer (n = 1), and others (n = 5). Voriconazole was indicated in 48 cases (68 %) as the first-line treatment for CPA and 23 patients previously received other antifungal therapies. Based on a composite of clinical, radiologic, serological, and mycologic criteria, good response was seen in 43 patients (60.6 %), no response was observed in 19 patients (26.8 %), and 4 cases (5.6 %) got worse. Five patients (7.0 %) were unassessable for efficacy. The common adverse events were visual disturbances (17 patients, 23.9 %), abnormal liver function test results (12 patients, 16.9 %), adverse psychological effects (3 patients, 4.2 %), and others (10 patients, 14.0 %). Treatment with voriconazole had to be stopped in 2 cases (2.8 %) because of serious adverse events (abnormal liver function test results). There was no association between adverse effects and trough voriconazole levels in serum. CONCLUSIONS: In Japan, voriconazole provides effective therapy of CPA in non-immunocompromised patients with an acceptable level of toxicity.


Subject(s)
Antifungal Agents/therapeutic use , Pulmonary Aspergillosis/drug therapy , Pyrimidines/therapeutic use , Triazoles/therapeutic use , Aged , Antifungal Agents/adverse effects , Chronic Disease/drug therapy , Dose-Response Relationship, Drug , Female , Humans , Japan , Male , Middle Aged , Prospective Studies , Pyrimidines/adverse effects , Treatment Outcome , Triazoles/adverse effects , Voriconazole
8.
Clin Microbiol Infect ; 12(8): 776-81, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16842573

ABSTRACT

Opportunistic infections in the oral cavity of the elderly may increase the incidence of systemic disease. The objective of this study was to investigate the differences in the oral bacterial flora between dependent elderly (inpatients) and independent elderly (community-dwelling residents). After multiple variables were taken into account, inpatients had significantly lower detection rates than community-dwelling residents for alpha-streptococci (p < 0.001) and Neisseria (p 0.004), and higher detection rates for Pseudomonas aeruginosa (p 0.024), methicillin-resistant Staphylococcus aureus (MRSA) (p 0.011) and Actinomyces spp. (p 0.005). Among inpatients, the requirement for a high degree of care was related negatively to detection of alpha-streptococci, but was related significantly to detection of P. aeruginosa (p 0.018) or MRSA (p 0.004). Tube-fed inpatients had a significantly lower detection rate for alpha-streptococci (p 0.041) and a higher detection rate for P. aeruginosa (p 0.004) than those who did not require tube feeding. Inpatients with a history of antibiotic use had a significantly lower detection rate for alpha-streptococci (p 0.049) and a higher detection rate for MRSA (p 0.007) than those without a history of antibiotic use. The detection rates for P. aeruginosa or MRSA in inpatients without alpha-streptococci were higher than in inpatients with alpha-streptococci after controlling for age and gender (P. aeruginosa, p 0.006; MRSA, p 0.001). Overall, detection of alpha-streptococci had an inverse correlation with the detection of P. aeruginosa and MRSA in the oral cavity and is likely to be an indicator of pathogenic bacterial infection.


Subject(s)
Bacteria/isolation & purification , Dental Plaque/microbiology , Aged , Aged, 80 and over , Female , Humans , Male , Methicillin Resistance , Pseudomonas aeruginosa/isolation & purification , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification , Streptococcus/isolation & purification
9.
J Int Med Res ; 34(1): 95-102, 2006.
Article in English | MEDLINE | ID: mdl-16604829

ABSTRACT

The aim of this study was to analyse the change in the oral cavity microflora of 14 patients who had undergone a radical prostatectomy for prostatic carcinoma. The detection of micro-organisms in the oral cavity was compared before and after the surgical procedure. Post-operative infection, defined as those patients who had increased Candida species counts and/or pathogenic bacteria only at the post-operative examination, was observed in 10 patients. Six patients showed increased Candida species counts at the post-operative examination compared with the pre-operative examination. In five patients, pathogenic bacterial species were detected at the post-operative examination but not at the pre-operative examination. One patient had detectable pathogenic bacterial species only at the post-operative examination along with increased Candida species counts. Our findings suggest that pre-operative oral hygiene to remove bacterial and Candida species from patients who are scheduled for surgical procedures is important for satisfactory clinical outcomes.


Subject(s)
Carcinoma/surgery , Gram-Negative Bacteria/pathogenicity , Infections/complications , Mouth/microbiology , Prostatectomy/adverse effects , Prostatic Neoplasms/surgery , Aged , Candida/isolation & purification , Candidiasis, Oral/complications , Candidiasis, Oral/microbiology , Carcinoma/pathology , Gram-Negative Bacteria/isolation & purification , Humans , Male , Middle Aged , Postoperative Complications/microbiology , Postoperative Period , Prostatectomy/methods , Prostatic Neoplasms/pathology
12.
Public Health ; 116(6): 341-6, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12407473

ABSTRACT

Smokers have been reported to exhibit a low awareness of their health. However, oral health awareness in smokers has not been fully studied. Having adequate oral care and high awareness of oral health from youth is necessary to prevent the deterioration of oral health in middle and old age. The aim of this study was to investigate the oral health status and oral health behaviour in young smokers. A survey composed of a questionnaire and an oral examination was administrated to adults aged 20-29 y who consulted dentists. The relationship between smoking behaviour and oral health status and oral health behaviour in subjects was analysed. In women, though no significant relationship between smoking behaviour and the number of decayed, missing, and filled teeth was seen, current smokers had significantly more decayed teeth, missing teeth and fewer filled teeth than ex-smokers and non-smokers. Current smokers tended to practice less oral health behaviour than non-smokers. In men, there was no significant relationship between smoking behaviour and each oral health status item. These findings suggested that the smoking group had lower oral health awareness than the non-smoking group in women.


Subject(s)
Dental Caries/epidemiology , Health Behavior , Health Knowledge, Attitudes, Practice , Smoking/epidemiology , Adult , Dental Caries/psychology , Dental Caries/therapy , Dental Health Services/statistics & numerical data , Diagnosis, Oral , Female , Humans , Japan/epidemiology , Male , Oral Health , Sex Factors , Smoking/psychology , Smoking Prevention , Socioeconomic Factors , Surveys and Questionnaires
13.
J Appl Microbiol ; 93(3): 487-91, 2002.
Article in English | MEDLINE | ID: mdl-12174048

ABSTRACT

AIMS: To analyse the relationship between oral bacteria and the health and functional status of the elderly. METHODS AND RESULTS: The bacteria species in the oral cavity of the elderly were examined. It was found that the bedridden subjects staying at two hospitals for long-term (HOBR) showed significantly lower detection rates of commensal bacteria species and significantly higher detection rates of Pseudomonas aeruginosa, of methicillin-resistant Staphylococcus aureus (MRSA) and of coagulase(-) Staph. aureus than those living independently (the independent). In addition, the detection rate of Haemophilus parainfluenzae in NUBR was discovered to be higher than that found in the independent. In HOBR, the detection rate of Ps. aeruginosa was significantly higher among in-patients who required continual care than those in need of partial care, while the detection rate of MRSA was significantly higher among in-patients with low serum albumin than those with normal serum albumin. CONCLUSIONS: Oral bacteria examination analysis proved that the risks of infection of some pathogenic bacteria species were correlated with functional status, physical function and nutritional state. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study suggests that the oral bacteria, especially pathogenic bacteria were influenced by the functional status of the elderly and the type and quality of the facilities for the bedridden, physical function and nutritional state.


Subject(s)
Bacteria/isolation & purification , Geriatric Assessment , Homes for the Aged , Immobilization/physiology , Mouth/microbiology , Nursing Homes , Activities of Daily Living , Aged , Aged, 80 and over , Bacteria/classification , Bacteria/pathogenicity , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , Dental Plaque/microbiology , Female , Humans , Male , Nutritional Status
14.
Leuk Lymphoma ; 42(3): 539-42, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11699422

ABSTRACT

A 53-year old man with systemic lymphadenopathy and hepatosplenomegaly was diagnosed with diffuse large B cell-lymphoma after inguinal lymph node biopsy. Anemia was noted, direct and indirect Coombs tests were positive, and the haptoglobin level was low. However, the bone marrow aspirate revealed erythroid aplasia. Co-existing autoimmune haemolytic anemia (AIHA) and pure red cell aplasia (PRCA) were diagnosed. In situ hybridization with Epstein-Barr virus (EBV) encoded small RNA (EBER) showed positive findings in lymphoma cells. Southern blot hybridization revealed immunoglobulin heavy chain gene rearrangement and a clonal EBV terminal repeat, indicating monoclonal proliferation of EBV in infected B cells. The patient was treated with CHOP, resulting in a complete remission (CR). AIHA and PRCA subsided after 3 courses of chemotherapy. In conclusion, this case demonstrates not only the association of B-cell lymphoma with autoimmune disorders but also the involvement of EBV in these conditions.


Subject(s)
Anemia, Hemolytic, Autoimmune/complications , Herpesvirus 4, Human/isolation & purification , Lymph Nodes/pathology , Lymphoma, B-Cell/complications , Lymphoma, Non-Hodgkin/complications , Red-Cell Aplasia, Pure/complications , Anemia, Hemolytic, Autoimmune/blood , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Hematopoietic Stem Cell Transplantation , Humans , In Situ Hybridization , Lymph Nodes/virology , Lymphoma, B-Cell/blood , Lymphoma, B-Cell/pathology , Lymphoma, B-Cell/therapy , Lymphoma, B-Cell/virology , Lymphoma, Non-Hodgkin/blood , Lymphoma, Non-Hodgkin/pathology , Lymphoma, Non-Hodgkin/therapy , Lymphoma, Non-Hodgkin/virology , Male , Middle Aged , Prednisone/administration & dosage , Red-Cell Aplasia, Pure/blood , Vincristine/administration & dosage
15.
Mutat Res ; 498(1-2): 107-15, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11673076

ABSTRACT

We previously determined the chemical structures of four 2-phenylbenzotriazole mutagens (PBTA-1, -2, -3 and -4) in blue rayon-adsorbed material from the Nishitakase River in Kyoto prefecture and the Nikko River in Aichi prefecture in Japan. On the basis of a synthesis study, these four PBTA derivatives were deduced to have originated from corresponding dinitrophenylazo dyes by reduction and chlorination. 2-[(2-Bromo-4,6-dinitrophenyl)azo]-5-[bis(2-acetoxyethyl) amino]-4-methoxyacetanilide (Color Index Name, Disperse Blue 79:1; CAS Registry Number, 75497-74-4) is a very common dinitrophenylazo dye used in textile dyeing factories. In the present study, we synthesized 2-[4-[bis(2-acetoxyethyl)amino]-2-(acetylamino)-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-5) from Disperse Blue 79:1 by reduction with sodium hydrosulfite and subsequent chlorination with sodium hypochlorite. On hydrolysis of PBTA-5 with alkali, 2-[2-(acetylamino)-4-[bis(2-hydroxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-6) was obtained. Both PBTA-5 and -6 were potent mutagens, inducing 723,000 revertants and 485,000 revertants per microgram of Salmonella typhimurium YG1024, respectively, in the presence of S9 mix. To clarify whether PBTA-5 and -6 exist in the environment, water samples were collected from five rivers flowing through regions where textile dyeing industries are developed. PBTA-6 was detected at levels of 3-134 ng/g blue rayon in all water samples that were examined. On the other hand, the amount of PBTA-5 in the samples was less than the detection limit.


Subject(s)
Cellulose/analogs & derivatives , Triazoles/analysis , Triazoles/chemistry , Triazoles/chemical synthesis , Adsorption , Cellulose/chemistry , Chromatography, High Pressure Liquid , Coloring Agents/chemistry , Fresh Water/chemistry , Indoles/chemistry , Japan , Mutagenicity Tests , Mutagens/analysis , Mutagens/chemical synthesis , Mutagens/toxicity , Organometallic Compounds/chemistry , Triazoles/toxicity
16.
Mutat Res ; 493(1-2): 75-85, 2001 Jun 27.
Article in English | MEDLINE | ID: mdl-11516717

ABSTRACT

We performed the in vitro micronucleus (MN) test on 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino)-4-[N-(2-cyanoethyl)-ethylamino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2), which are newly identified water pollutants from the Nishitakase river in Kyoto, Japan, and on their possible mother compounds (AZO DYE) and intermediates (non-ClPBTAs). We tested these compounds in the absence and presence of S9 mix in two Chinese hamster cell lines CHL and V79-MZ and scored MN, polynuclear and karyorrhectic (PN), and mitotic (M) cells. PBTA-2 in the absence of S9 mix induced the strongest responses in both cell lines. It was also a strong inducer of binucleate cells in PN cells in both cell lines, which suggested that it induced polyploidy. PBTA-1 showed clear positive results only in the absence of S9 mix and only in V79-MZ cells, inducing aneuploidy. In CHL cells AZO DYE-1 significantly induced MN cells in the presence of S9 mix, and AZO DYE-2 induced MN and PN cells, including binucleate cells and cells with a multilobed nucleus, in the absence of S9 mix. In V79-MZ cells, AZO DYE-1 and -2 induced primarily M cells in the presence of S9 mix. 9% of the M cells treated with 50 microg/ml AZO DYE-1 showed endoreduplication. AZO DYE-2 at 200 microg/ml condensed the chromatin in 100% of the cells. The non-ClPBTAs were a bit more cytotoxic than the other compounds and induced a slight increase in MN cells in both cell lines. Some of the chemicals tested induced a characteristic karyomorphology that might reflect abnormal cell division. Abnormalities of cell division could be detected in PN and M cells as well as in MN cells. Structure-activity relationships have also been discussed.


Subject(s)
Mutagens/toxicity , Triazoles/toxicity , Water Pollutants, Chemical/toxicity , Animals , Azo Compounds/isolation & purification , Azo Compounds/toxicity , Cell Line , Chromosome Aberrations , Coloring Agents/isolation & purification , Coloring Agents/toxicity , Cricetinae , In Vitro Techniques , Male , Micronucleus Tests , Microsomes, Liver/metabolism , Mutagens/isolation & purification , Rats , Triazoles/isolation & purification , Water Pollutants, Chemical/isolation & purification
17.
Br J Cancer ; 84(11): 1564-70, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11384109

ABSTRACT

Dendritic cells (DCs) loaded with tumour antigens have been successfully used to induce protective tumour immunity in murine models and human trials. However, it is still unclear which DC administration route elicits a superior therapeutic effect. Herein, we investigated the vaccine efficiency of DC2.4 cells, a murine dendritic cell line, pulsed with ovalbumin (OVA) in the murine E.G7-OVA tumour model after immunization via various routes. After a single vaccination using 1 x 10(6)OVA-pulsed DC2.4 cells, tumour was completely rejected in the intradermally (i.d.; three of four mice), subcutaneously (s.c.; three of four mice), and intraperitoneally (i.p.; one of four mice) immunized groups. Double vaccinations enhanced the anti-tumour effect in all groups except the intravenous (i.v.) group, which failed to achieve complete rejection. The anti-tumour efficacy of each immunization route was correlated with the OVA-specific cytotoxic T lymphocyte (CTL) activity evaluated on day 7 post-vaccination. Furthermore, the accumulation of DC2.4 cells in the regional lymph nodes was detected only in the i.d.-and s.c.-injected groups. These results demonstrate that the administration route of antigen-loaded DCs affects the migration of DCs to lymphoid tissues and the magnitude of antigen-specific CTL response. Furthermore, the immunization route affects vaccine efficiency.


Subject(s)
Antigens, Neoplasm/immunology , Cancer Vaccines/administration & dosage , Dendritic Cells , Animals , Disease Models, Animal , Female , Infusions, Parenteral , Injections, Intradermal , Injections, Subcutaneous , Mice , Mice, Inbred C57BL , Ovalbumin/administration & dosage , T-Lymphocytes, Cytotoxic/immunology
18.
Kekkaku ; 76(4): 357-62, 2001 Apr.
Article in Japanese | MEDLINE | ID: mdl-11398326

ABSTRACT

In vitro antimicrobial activities of ofloxacin (OFLX), levofloxacin (LVFX), ciprofloxacin (CPFX), and sparfloxacin (SPFX) were compared against various mycobacteria using the agar dilution method with 7H11 medium, and the following results were obtained. (1) These four new quinolones showed excellent antimicrobial activities against M. tuberculosis, M. kansasii, and M. fortuitum. (2) SPFX was most active against slowly growing mycobacteria. The activity against M. tuberculosis was in the order of SPFX > CPFX > LVFX > OFLX. The activity against M. kansasii was in the order of SPFX > LVFX > OFLX > or = CPFX. (3) On the other hand, CPFX was most active against rapidly growing mycobacteria. The activity against M. fortuitum was in the order of CPFX > SPFX > LVFX > OFLX. Considering the in vitro antimicrobial activities and the pharmacokinetics of these four drugs, they could achieve favorable clinical outcomes for all the patients with pulmonary infection due to M. tuberculosis or M. fortuitum and some of the patients with pulmonary infection due to M. kansasii or M. chelonae.


Subject(s)
Anti-Infective Agents/pharmacology , Ciprofloxacin/pharmacology , Fluoroquinolones , Levofloxacin , Mycobacterium/drug effects , Ofloxacin/pharmacology , Mycobacterium fortuitum/drug effects , Mycobacterium kansasii/drug effects , Mycobacterium tuberculosis/drug effects
19.
Mutat Res ; 492(1-2): 73-80, 2001 May 31.
Article in English | MEDLINE | ID: mdl-11377246

ABSTRACT

We have previously isolated five mutagens in blue rayon-adsorbed substances from water at a site below sewage plants in the Nishitakase River, in Kyoto, Japan, and identified two of them as 2-phenylbenzotriazole derivatives, 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino)-4-[(2-cyanoethyl)ethylamino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2). In the present study, we collected adsorbed materials on blue cotton (3 kg x 9 times) at the same location, and isolated a sufficient amount (97 microg) of one of the remaining three mutagens other than PBTA-1 and PBTA-2, for structural analysis, by multiple column chromatography. The structure of mutagen, accounting for 12% of the total mutagenicity of the blue rayon-adsorbed substances, was determined to be a PBTA-1 analogue, 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4). PBTA-4 is a potent mutagen, inducing 190,000 and 7,800,000 revertants of Salmonella typhimurium TA98 and YG1024 per microgram, respectively, in the presence of S9 mix. In addition to the water of the Nishitakase River, PBTA-4 was detected in water samples from two rivers that flow through other regions where textile-dyeing industries have been developed. Like other PBTA analogues, PBTA-4 might also be produced from azo dyes during industrial processes in dyeing factories and treatment at sewage plants.


Subject(s)
Azo Compounds/analysis , Fresh Water/chemistry , Mutagens/analysis , Triazoles/analysis , Animals , Chromatography, High Pressure Liquid , Coloring Agents/analysis , Male , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Mutagenicity Tests , Mutagens/toxicity , Rats , Rats, Sprague-Dawley , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Spectrophotometry, Ultraviolet , Triazoles/chemical synthesis
20.
Diabetes Res Clin Pract ; 52(2): 119-23, 2001 May.
Article in English | MEDLINE | ID: mdl-11311966

ABSTRACT

We analyzed serum concentrations of tumor necrosis factor-alpha (TNF-alpha) for their role in insulin resistance in 12 obese men with untreated Type 2 diabetes mellitus and in 6 age-and BMI-matched obese controls. Insulin resistance was expressed using the homeostasis model assessment (HOMA-R). Six of the patients were insulin-resistant (HOMA-R>5.0), while six were not (HOMA-R

Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus/physiopathology , Insulin Resistance , Obesity , Tumor Necrosis Factor-alpha/analysis , Adult , Aged , Diabetes Mellitus/blood , Diabetes Mellitus, Type 2/blood , Fasting/blood , Homeostasis , Humans , Middle Aged , Osmolar Concentration
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