Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 55
Filter
1.
Support Care Cancer ; 20(9): 2017-24, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22086405

ABSTRACT

PURPOSE: Frozen gloves (FG) are effective in preventing docetaxel-induced nail toxicity (DNT), but uncomfortable. The preventive effect of FG for DNT was compared using a standard (-25 to -30°C) or more comfortable (-10 to -20°C) preparation. METHODS: Breast cancer patients receiving docetaxel were eligible. Each patient wore an FG (prepared at -10 to -20°C for 90 min) for 60 min without replacement on the right hand. The left hand was protected by standard methods (FG prepared at -25 to -30°C overnight and worn for 90 min with replacement at 45 min). The primary endpoint was DNT occurrence at 5 months. Secondary endpoints included docetaxel exposure [cumulative dose and area under the blood concentration time curve (AUC)] until DNT occurrence and discomfort from FG. The pharmacokinetics of docetaxel was assessed. RESULTS: From 23 patients enrolled between December 2006 and June 2010, seven who received docetaxel for less than 5 months were excluded from evaluation. The median accumulated docetaxel dose was 700 mg/m(2) (340-1430 mg/m(2)). Within 5 months of FG use, none developed protocol-defined DNT in either hand. Two patients (13%) developed DNT at 7.2 and 7.3 months, respectively, both at -10 to -20°C. In the control hand (-25 to -30°C), discomfort occurred in 92% of the cycles, compared to 15% in the experimental hand (-10 to -20°C). Five patients (22%) experienced pain at -25 to -30°C, but none did at -10 to -20°C. The degree of docetaxel exposure was not related to DNT occurrence in our study. CONCLUSION: A convenient preparation of FG at -10 to -20°C is almost as effective as a standard preparation at -25 to -30°C, with significantly less discomfort.


Subject(s)
Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Gloves, Protective , Hypothermia, Induced/methods , Nail Diseases/prevention & control , Taxoids/adverse effects , Adult , Aged , Antineoplastic Agents/pharmacokinetics , Docetaxel , Female , Gloves, Protective/adverse effects , Humans , Hypothermia, Induced/adverse effects , Japan , Middle Aged , Nail Diseases/chemically induced , Nail Diseases/metabolism , Taxoids/pharmacokinetics
2.
Rev Sci Instrum ; 82(3): 033502, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21456732

ABSTRACT

The in situ calibration method for the impurity influx monitor (divertor) is experimentally examined. The total reflectance of the optical path from the focal point of the Cassegrain telescope to the first mirror is derived using a micro retroreflector array. An optical fiber with angled physical contact (APC) connectors reduces the return edge reflection. APC fibers and a multimode coupler increase the signal-to-noise ratio by about one order compared to that of triple-branched fibers and enable measurement of the wavelength dependence of the total reflectance of the optical system even after potential deterioration of mirror surfaces reduces reflectance.

3.
Diabetes Res Clin Pract ; 85(2): 208-12, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19576649

ABSTRACT

AIMS: HSP60 plays a protective role against heat, oxidative injury and ultraviolet. Recently, animal and clinical studies have suggested that HSP60 plays a role in various diseases. However, few epidemiological studies have demonstrated an association between HSP60 levels and type 2 diabetes mellitus. Therefore, an epidemiological study was conducted to examine the association of HSP60 with type 2 diabetes mellitus. METHODS: This study included 83 type 2 diabetes mellitus patients and 161 controls that were recruited from male employees who received annual health check-ups between 2005 and 2007. The serum HSP60 levels were measured using the ELISA method. RESULTS: Because the HSP60 levels were not detectable (<3.125 ng/mL) in 48.0% of the study subjects, HSP60 levels were divided into two categories (detectable or undetectable). A logistic regression analysis showed that the subjects in the undetectable had a 2.03 times higher risk of diabetes mellitus than those in the detectable after adjustment for age, BMI and rate of hypertension medication. CONCLUSIONS: This study was the first epidemiological study to demonstrate an association between type 2 diabetes mellitus and HSP60, thus suggesting that HSP60 may play an important role in the type 2 diabetes mellitus pathology.


Subject(s)
Chaperonin 60/blood , Diabetes Mellitus, Type 2/blood , Adiponectin/blood , Biomarkers/blood , Blood Pressure , Body Mass Index , Diabetes Mellitus, Type 2/physiopathology , Enzyme-Linked Immunosorbent Assay , Humans , Inflammation/blood , Male , Middle Aged , Reference Values , Regression Analysis
4.
Nihon Koshu Eisei Zasshi ; 48(8): 595-603, 2001 Aug.
Article in Japanese | MEDLINE | ID: mdl-11579483

ABSTRACT

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.


Subject(s)
Life Style , Nurses/psychology , Sleep Disorders, Circadian Rhythm/epidemiology , Work Schedule Tolerance/physiology , Adult , Female , Humans , Japan/epidemiology , Logistic Models , Middle Aged , Sleep , Surveys and Questionnaires , Time Factors
5.
Circ Res ; 89(3): 265-72, 2001 Aug 03.
Article in English | MEDLINE | ID: mdl-11485977

ABSTRACT

Diacylglycerol (DG) kinase (DGK) terminates signaling from DG, which serves as an activator of protein kinase C (PKC), by converting DG to phosphatidic acid. DGK is thus regarded as an attenuator of the PKC activity. In rats, five DGK isozymes have been cloned, but little is known about their role in the heart. In this study, the spatiotemporal expression of DGK isozymes was investigated in rat hearts under a normal condition and after myocardial infarction (MI) by in situ hybridization histochemistry and immunohistochemistry. In normal left ventricular myocardium, DGKalpha, DGKepsilon, and DGKzeta mRNAs were expressed evenly throughout the myocardium, although the DGKalpha expression was very low. In infarcted hearts, the expression of DGKzeta was enhanced in the peripheral zone of the necrotic area and at the border zone 3 and 7 days after MI, and to a lesser extent in the middle layer of the granulation tissue 21 days after MI. The enhanced DGKzeta expression in the infarcted and border areas could be attributed to granulocytes and macrophages. In contrast, the expression of DGKepsilon in the infarcted and border areas was lower than that in the viable left ventricle (LV) throughout the postoperation period. Furthermore, DGKepsilon expression in the viable myocardium 21 days after MI decreased significantly compared with left ventricular myocardium in the sham-operated rats and was completely restored by treatment with captopril. Our results demonstrate that three DGK isozymes are expressed in the heart and that each isozyme might have different functional characteristics in the healing and LV remodeling after MI.


Subject(s)
Captopril/pharmacology , Diacylglycerol Kinase/biosynthesis , Gene Expression/drug effects , Myocardial Infarction/enzymology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Blotting, Northern , Body Weight/drug effects , Diacylglycerol Kinase/genetics , Disease Models, Animal , Granulocytes/enzymology , Heart Ventricles/enzymology , Heart Ventricles/pathology , Immunohistochemistry , In Situ Hybridization , Isoenzymes/biosynthesis , Isoenzymes/genetics , Macrophages/enzymology , Male , Myocardial Infarction/pathology , Myocardium/enzymology , Myocardium/pathology , Organ Size/drug effects , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Rats , Rats, Wistar , Ventricular Remodeling/drug effects
6.
J Control Release ; 73(2-3): 279-91, 2001 Jun 15.
Article in English | MEDLINE | ID: mdl-11516505

ABSTRACT

In order to achieve a zero-order release of protein drugs, we have developed a new drug delivery system using silicone, which is named the covered-rod-type formulation. Preparation of the covered-rod-type formulation was conducted under mild conditions without heat treatment or the use of organic solvents. The covered-rod-type formulation released human serum albumin (HSA) or interferon (IFN) at a constant rate for 30-100 days in vitro without significant initial burst. When the IFN covered-rod-type formulation was implanted in nude mice, the serum IFN concentration was maintained at a constant level during the period of observation, i.e., 28 days. The covered-rod-type formulation enabled precise control of the release of the protein drugs and would be expected to increase the duration of the drug effect and to reduce the frequency of administration and side effects.


Subject(s)
Drug Delivery Systems , Proteins/administration & dosage , Silicones/administration & dosage , Animals , Delayed-Action Preparations , Female , Interferons/administration & dosage , Interferons/blood , Interferons/chemistry , Mice , Mice, Inbred BALB C , Particle Size , Proteins/chemistry , Serum Albumin/administration & dosage , Serum Albumin/chemistry
7.
Proc Natl Acad Sci U S A ; 98(16): 9226-30, 2001 Jul 31.
Article in English | MEDLINE | ID: mdl-11459933

ABSTRACT

Normal levels of CD4(+) regulatory T cells are critical for the maintenance of immunological homeostasis and the prevention of autoimmune diseases. However, we now show that the expansion of CD4(+) regulatory T cells in response to a chronic viral infection can lead to immunosuppression. Mice persistently infected with Friend retrovirus develop approximately twice the normal percentage of splenic CD4(+) regulatory T cells and lose their ability to reject certain tumor transplants. The role of CD4(+) regulatory T cells was demonstrated by the transmission of immunosuppression to uninfected mice by adoptive transfers of CD4(+) T cells. CD4(+) T cells from chronically infected mice were also immunosuppressive in vitro, inhibiting the generation of cytolytic T lymphocytes in mixed lymphocyte cultures. Inhibition occurred at the level of blast-cell formation through a mechanism or mechanisms involving transforming growth factor-beta and the cell surface molecule CTLA-4 (CD152). These results suggest a possible explanation for HIV- and human T cell leukemia virus-I-induced immunosuppression in the absence of T cell depletion.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Friend murine leukemia virus/physiology , Immune Tolerance , Retroviridae Infections/immunology , Adoptive Transfer , Animals , Mice , Mice, Inbred C57BL
8.
Environ Health Prev Med ; 6(2): 121-6, 2001 Jul.
Article in English | MEDLINE | ID: mdl-21432249

ABSTRACT

OBJECTIVES: The author conducted an ecological study to examine prefectural differences in ENMR and the related factors in Japan, using two new indicators; birth weight (BW) adjusted ENMR and expected ENMR by BW distribution. METHOD: Correlate analysis of data from national vital statistics and some indicators of medical care services among 47 prefectures edited by the Ministry of Health and Welfare, Japan were conducted. BW-adjusted ENMR and expected ENMR by BW, as well as other indicators, were prepared for statistical analysis. RESULT: Crude and BW-adjusted ENMRs were significantly correlated with ENMRs for low birth weight (LBW) and very low birth weight (VLBW) early neonates (p<0.01). The number of Obstetrics and Gynecology (OB/GYN) physicians was negatively correlated with BW adjusted ENMR. CONCLUSION: Crude and BW-adjusted ENMRs were affected mainly by LBW and VLBW early neonate specific ENMR, but not by the rate of LBW. The variation of ENMR among prefectures in Japan is attributable to the number of OB/GYN physicians. The present findings suggest that emphasis should be laid upon enhancement of regional perinatal care systems.

9.
J Control Release ; 66(1): 49-61, 2000 May 03.
Article in English | MEDLINE | ID: mdl-10708878

ABSTRACT

A novel technique, by which protein drugs effective in small doses can be released over a long period, was developed using silicone and a water-soluble substance. In this study, interferon (IFN) was used as a model of the protein drugs. The IFN-silicone formulation released IFN over long periods of time in vitro and suppressed tumor growth in nude mice for about 100 days after a single administration. This indicates that physiologically active IFN is released over a prolonged period of time from the IFN-silicone formulation in vivo. Silicone formulations are expected to be a practically feasible sustained-release formulation.


Subject(s)
Delayed-Action Preparations , Interferon-alpha/administration & dosage , Silicones/chemistry , Animals , Dimethylpolysiloxanes , Female , Glycine/chemistry , Interferon-alpha/pharmacokinetics , Interferon-alpha/therapeutic use , Kinetics , Mice , Mice, Nude , Microscopy, Confocal , Neoplasm Transplantation , Osmotic Pressure , Particle Size , Powders , Solubility , Tumor Cells, Cultured
10.
Surg Today ; 29(4): 338-43, 1999.
Article in English | MEDLINE | ID: mdl-10211564

ABSTRACT

To evaluate the effect of interferon-gamma-gene-transduced cells, DS mice were inoculated into their footpads with syngeneic mammary adenocarcinoma SC42 admixed with interferon-gamma producing mammary adenocarcinoma SC115Kgamma, which had been established by an interferon-gamma-gene transduction in another syngeneic mammary adenocarcinoma SC115 using retroviral vectors. These mice rejected both tumor cells and developed resistance to subsequent challenges with either SC115 or SC42 cells inoculated into their opposite posterior footpads. These results thus indicate that systemic immunological memory to each of the independent tumor cell lines developed in these mice. Although the SC42 cells admixed with irradiated SC115Kgamma cells were rejected by these mice, the SC42 cells admixed with irradiated SC115neoR, in which the neo-gene had been transduced, were observed to proliferate. Tumor rejection was reversed by an in vivo administration of anti-interferon-gamma antibody, thus suggesting that locally produced interferon-gamma plays an important role in tumor elimination and immunological memory induction. In conclusion, interferon-gamma-gene-transduced tumor cells are therefore considered to have a therapeutic potential for other types of malignant tumor cell lines.


Subject(s)
Adenocarcinoma/immunology , Immunologic Memory , Interferon-gamma/genetics , Mammary Neoplasms, Experimental/immunology , Transduction, Genetic , Adenocarcinoma/pathology , Animals , Cytotoxicity, Immunologic , Disease Models, Animal , Female , Interferon-gamma/immunology , Male , Mice , Mice, Inbred Strains , Tumor Cells, Cultured
11.
J Surg Oncol ; 67(4): 221-7, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9579368

ABSTRACT

BACKGROUND AND OBJECTIVES: In order to evaluate the regulatory effect of cyclophosphamide (CPA) on active specific immunization (ASI)-induced antitumor immunity, we examined the timing of CPA (100 mg/kg) with ASI, and focused on whether CPA given after ASI augments antitumor immunity by modulation of Th1 commitment of CD4+ T cells. METHODS: We examined the effect of CPA combined with ASI using sonicated tumor supernatant (SS) and recombinant interleukin-1 beta (rIL-1 beta). RESULTS: Survival of i.p. tumor inoculated mice after ASI (days -12, -9, and -6) followed by 100 mg/kg CPA (day -3) (ASI-CPA) was significantly prolonged compared with that of mice treated with ASI alone, whereas CPA (day -15) treatment before ASI (CPA-ASI) completely abrogated the survival prolongation by ASI alone. In early stage (day 0) after ASI-CPA treatment, the CD4+ T cells were determined to play an important role in the protective immunity for the following reasons: 1) the CD4+/CD8+ ratio of spleen cells from immunized mice was higher than that of the control or CPA alone treated group; and 2) the tumor neutralizing activity of fresh spleen cells was abrogated by CD4+ T-cell depletion in vitro. CD4+ T cells of mice treated with ASI-CPA produced more interferon (IFN)-gamma and IL-2 and less IL-4 than those of the ASI alone group. CONCLUSIONS: These results suggest that the protective immunity induced by ASI was augmented through the modification of the Th1 and Th2 balance by CPA injection after ASI.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cyclophosphamide/administration & dosage , Plasmacytoma/immunology , Th1 Cells/immunology , Vaccination , Animals , CD4-CD8 Ratio , CD4-Positive T-Lymphocytes/cytology , Flow Cytometry , Immunity, Cellular , Interferon-gamma/biosynthesis , Interleukin-2/biosynthesis , Male , Mice , Mice, Inbred BALB C , Spleen/cytology , Spleen/immunology , Th2 Cells/immunology
12.
Biotherapy ; 11(4): 223-8, 1998.
Article in English | MEDLINE | ID: mdl-9950097

ABSTRACT

In order to analyse the effector population in an immunization model, we treated BALB/c mice with intraperitoneal (i.p.) active specific immunization (ASI), which consists of interleukin (IL)-1-beta and sonicated tumor supernatant (SS) of a plasmacytoma MOPC-104E followed by i.p. injection of cyclophosphamide (CY). This ASI-CY treatment provoked a protective immunity against i.p. tumor inoculation more strongly than that of ASI alone. The main effector cells in tumor neutralizing assay were CD4+ T cells at this pont. The number of spleen cells of the ASI-CY treated mice were significantly lower than that of ASI alone treated mice but it increased significantly 6 days thereafter while this increase was not observed on the mice treated with ASI alone. The spleen cells of the ASI-CY treated mice responded to SS in vitro in the presence of IL-2, more profoundly in CD4 enriched population which produced high amount of TNF-alpha. In vivo tumor-neutralizing activity at a later stage was dependent on CD8+ T cells in addition to CD4+ T cells. These results suggest that antitumor activity by ASI and CY is transduced by sequential population shift from CD4 alone to both of CD4 and CD8.


Subject(s)
Antineoplastic Agents, Alkylating/administration & dosage , Cyclophosphamide/administration & dosage , Immunotherapy, Active/methods , Plasmacytoma/drug therapy , Plasmacytoma/therapy , Adjuvants, Immunologic/administration & dosage , Animals , Antigens, Neoplasm/administration & dosage , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Combined Modality Therapy , Interleukin-1/administration & dosage , Interleukin-2/administration & dosage , Male , Mice , Mice, Inbred BALB C , Plasmacytoma/immunology , Recombinant Proteins/administration & dosage , Spleen/immunology , Time Factors , Tumor Necrosis Factor-alpha/biosynthesis
13.
J Immunol ; 158(11): 5338-48, 1997 Jun 01.
Article in English | MEDLINE | ID: mdl-9164954

ABSTRACT

Non-MHC-restricted rejection mechanisms against the murine MHC-negative F9 embryonal carcinoma cells were analyzed. Strains of C57BL/6 (B6) background were resistant to the tumors irrespective of H-2 haplotypes, while others, including BALB/c background, were susceptible. This resistance was suggested to be mediated primarily by the host thymus-dependent alphabeta T cells, since both athymic B6 nude and normal B6 mice depleted with alphabeta T cells showed susceptible phenotype. The difference of the nature of alphabeta T cells infiltrating in H-2-identical B6- and BALB.B-derived tumors was then comparatively analyzed. It was revealed that unique T cells with NK1+ CD4- CD8- (double negative (DN)) alphabeta TCR+ phenotype were accumulated significantly in B6, but few in BALB.B mice. The population freshly isolated from the F9 tumor tissues preferentially expressed potent IL-4 mRNA, and was suggested to be mostly responsible for the endogenous IL-4 production. Indeed, the injection of either anti-NK1.1 or anti-IL-4-neutralizing Ab into the normal B6 rendered them significantly susceptible to the tumor cells. These results strongly suggested that NK1+ DN alphabeta T cells were responsible primarily for the rejection mechanisms against F9 tumors. Histologically, F9 tumors in B6 mice were characterized by abundant macrophage infiltration and massive tumor necrosis, neither of which was observed in those in BALB.B nor B6 mice preinjected with anti-IL-4 Ab, indicating that both histologic features in the resistant strain were dependent on the endogenous IL-4. Present results provide one of the first instances in which a recently emerging minor T cell subpopulation, thymus-dependent NK1+ DN alphabeta T cells, plays an essential role in anti-tumor responses in vivo.


Subject(s)
Carcinoma, Embryonal/immunology , T-Lymphocyte Subsets/immunology , Testicular Neoplasms/immunology , Animals , Antigens/immunology , Antigens, Ly , Antigens, Surface , CD4 Antigens/immunology , CD8 Antigens/immunology , Flow Cytometry , Immunity, Innate/genetics , Immunity, Innate/immunology , Immunophenotyping , Lectins, C-Type , Major Histocompatibility Complex/immunology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , NK Cell Lectin-Like Receptor Subfamily B , Proteins/immunology , Receptors, Antigen, T-Cell, alpha-beta/immunology
14.
Surg Today ; 27(6): 571-3, 1997.
Article in English | MEDLINE | ID: mdl-9306555

ABSTRACT

Active specific immunotherapy was examined in BALB/c mice using sonicated tumor extract(SE) from plasmacytoma MOPC104E or interferon-gamma-(IFN-gamma)-gene-transduced MOPC104E (Mu gamma), employing interleukin-1 (IL-1) as an adjuvant. Subcutaneous (s.c.) MOPC104E tumor growth was significantly suppressed in mice given a single preimmunization of IL-1 plus Mu gamma-SE, 9 days prior to inoculation, whereas the tumor growth in mice similarly pretreated with IL-1 alone or IL-1 plus MOPC104E-SE(MOPC-SE) was not affected; the mean tumor diameters on day 21 being 6.8 mm, 15.3 mm, and 13.2 mm, respectively. Two-dose preimmunization with Mu gamma-SE alone or IL-1 alone given 10 and 7 days prior to s.c. inoculation also resulted in profound suppression of tumor growth compared to the control. As postsurgical immunization, MOPC104E cells were injected into the foot pads of mice, followed by amputation of the tumor-bearing foot 20 days later, then treatment with IL-1 plus MOPC-SE or IL-1 plus Mu gamma-SE on days 4, 7, and 10 after the amputation. The mean survival of the mice treated with IL-1 plus Mu gamma-SE was significantly prolonged compared to that of the mice treated with IL-1 plus MOPC-SE, at 90.3 days vs 40.9 days, respectively (P < 0.05 by the Cox-Mantel test). These results suggest that SE prepared from IFN-gamma-gene-transduced MOPC104E is more effective for active specific immunotherapy than SE prepared from MOPC104E.


Subject(s)
Cancer Vaccines , Immunotherapy, Active , Interferon-gamma , Plasmacytoma/therapy , Transduction, Genetic , Animals , Disease Models, Animal , Interferon-gamma/genetics , Interleukin-1/therapeutic use , Male , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Tumor Cells, Cultured
15.
J Immunol ; 157(9): 3925-35, 1996 Nov 01.
Article in English | MEDLINE | ID: mdl-8892624

ABSTRACT

NK1+ double negative (DN) alphabeta T cells were present in the peritoneal exudate cells (PEC) of both normal and athymic B6 mice, accounting for as much as 25% of the total T cells, while their numbers were far less in the PEC of BALB/c and (BALB/c x B6)F1 mice. IL-2-dependent clones established from the DN alphabeta T cell population in the PEC of IL-2 receptor alpha-chain transgenic B6 mice exhibited potent cytotoxicity against a series of B cell lineage leukemias and myelomas, such as CD5+BCL1 and MOPC, without affecting NK-susceptible targets. The cytotoxicity of the clones against BCL1 and MOPC was specifically inhibited by anti-CD3, anti-alphabetaTCR, or anti-relevant Vbeta (Vbeta8) Ab, but not by control Abs, indicating that it was mediated by the specific alphabetaTCR/CD3. Other BALB/c-derived target cells expressing both MHC class I and class II were not affected, and neither Ab against them affected the cytotoxicity, strongly suggesting that the cytotoxicity of NK1+ DN alphabeta T cell clones was independent of the particular MHC Ags. The clones produced IFN-gamma, but little IL-2 or IL-4, in response to anti-CD3 stimulation, to the susceptible, but not resistant, targets, and to IL-12. The clones exhibited TCRalpha (Valpha8) distinct from an invariant TCRalpha (Valpha14) reported to dominate in thymic NK1+ alphabeta T cells. The presence of DN alphabeta T cells with similar functional features in the normal PEC was confirmed by the short term stimulation in vitro. The present results along with other recent reports strongly suggested that, like the mainstream alphabeta T cells, the NK1+ DN alphabeta T cell population consisted of functionally heterogeneous subsets.


Subject(s)
Ascitic Fluid/immunology , Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor , Interferon-gamma/biosynthesis , Killer Cells, Natural/immunology , Leukemia, B-Cell/immunology , Multiple Myeloma/immunology , Receptors, Antigen, T-Cell, alpha-beta/immunology , T-Lymphocytes, Cytotoxic/immunology , Amino Acid Sequence , Animals , Base Sequence , Clone Cells/immunology , Cytotoxicity, Immunologic , H-2 Antigens/immunology , Humans , Interferon-gamma/metabolism , Killer Cells, Natural/metabolism , Leukemia, B-Cell/pathology , Lymphocyte Count , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Nude , Mice, Transgenic , Molecular Sequence Data , Multiple Myeloma/pathology , Muromonab-CD3/pharmacology , Receptor-CD3 Complex, Antigen, T-Cell/immunology , Receptors, Interleukin-2/genetics , Tumor Cells, Cultured
16.
J Surg Oncol ; 62(2): 78-85, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8649045

ABSTRACT

The possibility of active specific immunotherapy using interleukin-1 (IL-1) plus sonicated tumor supernatant (SS) was examined in a murine tumor model. The growth of intraperitoneally or subcutaneously inoculated plasmacytoma MOPC104E, which is syngeneic to BALB/c mice, was significantly suppressed by intraperitoneal pretreatment with IL-1 and SS from MOPC104E cells (MOPC-SS), on days 10, 7, and 4 before tumor inoculation. Pretreatment with IL-1 plus MOPC-SS or MethA-SS (SS from MethA cells) suppressed the growth of subcutaneous tumor of only the corresponding tumor cells, indicating the development of tumor-specific immunity in vivo. The splenic cells of immunized mice with IL-1 and MOPC-SS showed tumor neutralizing activity. However, their tumor neutralizing activity was abrogated when they were treated in vitro with anti-Thy1.2 or anti-L3T4 plus complement. Moreover, when combined with indomethacin per oral, IL-1 plus MOPC-SS significantly suppressed the growth of established subcutaneous tumor and prolonged survival of post-operative mice. These results suggest that this new type of active specific immunotherapy could be a useful method for cancer immunotherapy, especially when combined with oral indomethacin.


Subject(s)
Antigens, Neoplasm/therapeutic use , Interleukin-1/pharmacology , Neoplasms, Experimental/immunology , Neoplasms, Experimental/therapy , Vaccination/methods , Animals , Antibodies, Monoclonal/therapeutic use , Chemical Precipitation , Dose-Response Relationship, Drug , Fibrosarcoma/chemistry , Fibrosarcoma/therapy , Interleukin-2/pharmacology , Male , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Neoplasms, Experimental/chemistry , Plasmacytoma/chemistry , Plasmacytoma/therapy , Proportional Hazards Models , Sonication , Spleen/cytology , Survival Analysis , Tumor Cells, Cultured
17.
Nihon Kyobu Shikkan Gakkai Zasshi ; 33(12): 1355-60, 1995 Dec.
Article in Japanese | MEDLINE | ID: mdl-8821987

ABSTRACT

Periodic breathing (PB) during sleep at an altitude of 5100 m was studied with a pulse oximeter. The subjects were six Japanese who stayed at about 5100 m (group A), nine Japanese who climbed above 7000 m (group B) and eight Sherpase (high landers). Among Japanese subjects, PB was observed most often in group A. The sherpas almost never breathed periodically. PB and symptoms of acute mountain sickness correlated positively among Japanese subjects. The cycle time of PB did not differ among the three groups. PB may be related to acclimatization.


Subject(s)
Acclimatization/physiology , Altitude Sickness/physiopathology , Altitude , Respiration/physiology , Acute Disease , Adult , Humans , Middle Aged
18.
Clin Immunol Immunopathol ; 74(3): 217-22, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7859411

ABSTRACT

The relationship between the level of gamma delta T cells and cellular immunity of T lymphocytes was assessed in the peripheral blood of active sarcoidosis patients and healthy controls. We divided the active sarcoidosis patients into two groups: a group of patients with a normal distribution of circulating gamma delta T cells (group A; n = 11, less than 8.2% lymphocytes) and another group with increased gamma delta T cell levels (group B; n = 11, greater than 8.2% lymphocytes). The proportion and absolute count of CD4+ lymphocytes in group B (28.6 +/- 11.2%, 374.1 +/- 193.8/microliters) were remarkably smaller than control subjects (45.7 +/- 6.8%, 818.3 +/- 290.2/microliters, P < 0.001, P < 0.002, respectively). Group A, however, showed a moderate reduction in CD4+ lymphocytes when compared with controls. Serial measurements of T cell subtypes were performed on five patients in group B. gamma delta T cells and CD4+ lymphocytes were inversely correlated over the observation period which ranged from 2 to 18 months. When peripheral blood T cells were stimulated with PHA or PPD in vitro, the responses were weaker in group B compared with both group A and control subjects. These results suggest that the increase in circulating gamma delta T cells in sarcoidosis closely relates to a defect in cellular immunity which progresses during the disease process.


Subject(s)
Receptors, Antigen, T-Cell, gamma-delta/immunology , Sarcoidosis/immunology , T-Lymphocytes/immunology , Adult , CD4-Positive T-Lymphocytes/immunology , Female , Humans , Immunity, Cellular/immunology , Immunophenotyping , Lymphocyte Activation/immunology , Male , Middle Aged , Mitogens/pharmacology , Phenotype , Sarcoidosis/blood
19.
Kekkaku ; 69(11): 671-80, 1994 Nov.
Article in Japanese | MEDLINE | ID: mdl-7837720

ABSTRACT

From January 1991 to December 1992, 419 patients with pulmonary tuberculosis were initially treated at Fukujuji Hospital. Among them, 190 patients, who were younger than 80 years old and had pulmonary tuberculosis with cavities or infiltration of extension 2 or 3, and/or were sputum-smear positive, had been treated by 6-month short course regimen containing pyrazinamide, 2HRS(E)Z/4HRE. And were eligible for the evaluation of the clinical usefulness of pyrazinamide-containing regimen for the initial treatment of pulmonary tuberculosis. The dose of pyrazinamide was 1.2 g per day irrespective of body weight. The patients of this treatment group consisted of 151 males and 39 females, and mean age of the males was 45.3 and that of the females was 43.8 years old. At the start of the treatment, 74% of the cases were smear positive, 70% were cavitary, and 6 cases each showed primary resistance to isoniazid and to streptomycin, respectively, and only one case showed resistance to both of isoniazid and streptomycin. There was no primary resistant case to either rifampicin or ethambutol. Bacteriologic negative conversion rates were 95% and 90% after 2 months of treatment by PZA-containing regimen and by the standard regimen, respectively, and treatment durations required to achieve the negative conversion of all cases were 3 and 6 months for respective regimens. Of 90 patients who completed 6-month PZA-containing regimen and could be followed-up, only one bacteriologic relapse (1.1%) was noticed. Elevation of serum GPT level higher than 150 IU/ml during the treatment was noticed in 6.3% of 175 cases under PZA-containing regimen in comparison with 4.0% of 174 cases under the standard regimen (not significant). The interval between the onset of the treatment and the detection of abnormal liver function was much shorter (mean 31.3 days) in the PZA-containing regimen than in the standard regimens (mean 63.4 days). Hyperuricaemia (> 10 mg/ml) was noticed in 46.7% of 57 males and 59.4% of 19 females tested, but pyrazinamide was not discontinued in any case due to arthralgia. These results clearly show that pyrazinamide can be used rather safely for Japanese tuberculosis patients. If the pyrazinamide-containing regimen [2HRS(E)Z/4HRE] is adopted as the new standard regimen in place of on-going standard regimen in Japan, 6HRS(E)/3HR, the duration of chemotherapy could be shortened by three months with the same level of both efficacy and safety. We recommended pyrazinamide-containing 6-month regimen, 2HRS(E)Z/4HRE, as the new standard regimen for the initial treatment of pulmonary tuberculosis.


Subject(s)
Pyrazinamide/administration & dosage , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Aged , Drug Therapy, Combination , Ethambutol/administration & dosage , Female , Humans , Isoniazid/administration & dosage , Male , Middle Aged , Rifampin/administration & dosage , Streptomycin/administration & dosage
20.
Kekkaku ; 69(10): 587-92, 1994 Oct.
Article in Japanese | MEDLINE | ID: mdl-7799569

ABSTRACT

Mycobacterium kansasii infection responds well to antituberculous drugs, and in the initial phase of treatment, many patients with M. kansasii infection are regarded as tuberculosis. This study was carried out to know whether the regimen of chemotherapy be continued or changed after the confirmation of diagnosis as M. kansasii infection. The treatment result of 107 cases with M. kansasii infection of the lung encountered at Fukujuji Hospital was compared with that of pulmonary tuberculosis. Sputum culture of all patients treated with drug regimens containing RFP converted to negative within 3 months after starting chemotherapy, while sputum culture of many patients treated with regimens not containing RFP converted to negative 4 months or later after the start of chemotherapy. Hence, the effectiveness of RFP in treating M. kansasii infection was confirmed. Among 65 patients with no relapse during a follow-up period of at least one year after the completion of chemotherapy, 58 patients (89.2%) were treated with drug regimens containing INH and RFP, and the treatment of 40 patients (61.5%) was finished within 12 months. Among three patients deteriorated during chemotherapy or relapsed within one year after the completion of chemotherapy, two patients were treated with drug regimens containing RFP and one of them had serious complications. The chemotherapy regimen for tuberculosis is considered to be sufficient for the initial treatment of pulmonary disease caused by M. kansasii.


Subject(s)
Antitubercular Agents/therapeutic use , Mycobacterium Infections, Nontuberculous/drug therapy , Tuberculosis, Pulmonary/drug therapy , Adult , Aged , Female , Humans , Male , Middle Aged , Rifampin/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...