[High-dose chemotherapy rescued with peripheral blood stem cell transplantation for high-risk patients with breast cancer].
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Adult↗
Biomedical subjects
Y Kimoto
Publications and source records attributed to Y Kimoto.
A possibility of all mRNA expression in a human single lymphocyte.
Expression of gene transcripts for 16 proteins was investigated in a human single lymphocyte using RT-nested PCR method. Examined mRNAs were for IL-2, CD8, progesterone receptor, parathyroid hormone, gastrin, glucagon, cholecystokinin/pancreozymin, insulin, enkephalin, thyroid stimulating hormone, MUC1, MAGE1, pregnancy-specific beta-1 glycoprotein 4, phenylethanolamine-N-methyltransferase, beta B3-crystallin and HOX4A. Most of the proteins were thought to be functionally irrelevant to a lymphocyte. All of them were detected in a lymphocyte without exception. The result suggests that there is a possibility of all mRNA expression in a human single cell.
Humans↗
Senile plaques and other senile changes in the brain of an aged American black bear.
A female American black bear (Euarctos ursus americanus) over 20 years old had shown epileptiform neurologic signs starting in March 1992 and was found dead unexpectedly 8 months later. At necropsy, pulmonary and intrabronchial hemorrhage was noted. In the brain, the leptomeninges exhibited slight thickening, and petechiae were evident in the hippocampus. Histopathologic examination of the brain revealed several senile changes: numerous senile plaques, amyloid deposition in cerebromeningeal arterioles, mineral deposition in the pallidum, and numerous corpora amylacea in the cerebellum.
Aging↗
Gene transcripts of eleven proteins with specific functions are all detected in human normal cells and tumor cell lines: a possible DNA-->RNA basal constant flow.
Existance of messenger ribonucleic acids of eleven functionally differentiated proteins in normal human cells and tumor cell lines was investigated using reverse transcription--nested polymerase chain reaction method. Examined gene transcripts were those of progesterone receptor, estrogen receptor, interleukin 2, CD8, parathyroid hormone, cholecystokinin/pancreozymin, glucagon, insulin, adrenocorticotropic hormone, enkephalin and thyroid stimulating hormone. In RT-PCR almost all primers were originally designed and sequences of PCR products were confirmed by the Sanger's method. Investigated cells were normal human peripheral mononuclear cells and their subsets, lymphokine-activated killer cells, gastric mucosal cells, sperm and fifteen established tumor cell lines. All of the examined mRNAs were detected in all of the above cell groups. Therefore, cells of independent tissues or tumors share same kinds of mRNA such as steroid hormone receptors, cytokine, lymphocyte surface molecule and parathyroid, digestive and cerebral hormones. These findings strongly suggest that every cell can express every mRNA. Beneath the cell differentiation there may exist a DNA-->RNA basal constant flow, the arrow of time captured in a cell.
Base Sequence↗
Use of human leukocyte antigen-mismatched allogeneic lymphokine-activated killer cells and interleukin-2 in the adoptive immunotherapy of patients with malignancies.
Clinical effects and side effects were studied in the adoptive immunotherapy of patients bearing malignant diseases using human leukocyte antigen (HLA)-mismatched allogeneic lymphokine-activated killer (LAK) cells. Allogeneic LAK cells were induced from peripheral blood lymphocytes (PBL) of normal donors by means of initial stimulation with pokeweed mitogen (PWM). Six of 15 patients applied in the adoptive immunotherapy showed clinical effects such as partial or complete regression of pulmonary metastasis, pleural effusion and primary tumor. All pulmonary metastatic lesions were eliminated in one case by this adoptive immunotherapy combined with chemotherapy. Generally toxic effects were chillness, fever and general fatigue which were reversible, and no allergic side effects occurred even though allogeneic LAK cells were injected frequently except one patient who showed preshock like symptom accompanied with leukocytopenia and continuous hypotension immediately after infusion but was finally rescued. In the patients who received more than 10(11) of allogeneic LAK cells, anti-HLA class I antibodies appeared without any evidence of autoantibody. However, immunological side effects were never experienced after injection of allogeneic LAK cells even when the anti-HLA class I antibodies appeared in the patients. Taken together, allogeneic LAK cells could be considered as alternative therapy for patients with malignancies who could not supply sufficient materials of autologous LAK cells.
Adult↗
Penile prostheses for the management of the neuropathic bladder and sexual dysfunction in spinal cord injury patients: long term follow up.
During the last 10 years, 90 penile prostheses were implanted in 82 patients with spinal cord injury. Surgery was done 1 month to 25 years (average 4.8 years) after the injury. The follow up period ranged from 1 to 10 years (average 4 years). A prosthesis was implanted for urinary management in 51 patients (62%), for sexual dysfunction in 10 patients (12%) and for both purposes in 21 patients (26%). Ninety-three per cent of the patients who used the implant for urinary management and 64% of the patients who used it for sexual dysfunction were satisfactory. We experienced three extrusions and nine surgical removals due to pain, difficulty of catheterisation and infection (the complication rate was 13.3%). Generally speaking, a penile prosthesis improves the quality of life of patients with spinal cord injury significantly; however, extrusion and infection are still significant problems.
Adolescent↗
[Therapeutic strategy for anaplastic carcinoma and malignant lymphoma of the thyroid].
Therapeutic strategies for anaplastic carcinoma and malignant lymphoma of the thyroid are reviewed. Because of the rarity of both diseases among thyroid malignancies, the generally accepted treatment policy has not been established, although the importance of radiation therapy and chemotherapy has been well recognized for the treatment of both diseases. Hyperfractionated radiation therapy combined with suitable systemic chemotherapy will counter anaplastic thyroid carcinoma and prolong survival. Most patients with thyroid malignant lymphoma have better prognoses than anaplastic carcinoma patients. But delayed diagnosis and inadequate treatment still results in a poor prognosis, in spite of the more treatable characteristics of thyroid malignant lymphoma than anaplastic thyroid carcinoma. At present, early detection of the tumor and selection of a suitable therapy is necessary for the improvement of prognosis, and further clinical studies are required to establish effective regimens for multidisciplinary treatment.
Carcinoma↗
Influence of physiological concentration of progesterone on CD(4+)- and CD(8+)-activated lymphocytes with interleukin 2 and autologous plasma: difference between healthy donors and patients bearing malignant tumors.
The influence of progesterone at the physiological concentration on normal donor and malignant patient peripheral blood lymphocytes incubated with interleukin 2 (IL-2) was investigated. Analysis of the phenotypes of IL-2-activated lymphocytes revealed that there was a difference in the positive rates of CD4+ and CD8+ cells between normal donors and patients with malignancies. Activated lymphocytes of normal adults older than 35 years of age consisted of 60-100% of CD4+ cells and 0-30% of CD8+ cells. Donors younger than 35 years of age showed a positive rate of CD4+ cells, ranging from 0-100%, while CD8+ cells were between 0-60%. However, in patients with malignancies both CD4+ and CD(8+)-activated lymphocytes diffused from 0-100%. Activated lymphocytes of most patients were CD8+ cell dominant, which reversed the CD4+/CD8+ ratio. Almost all patients at clinical stage IV showed a deviation of the positive rates of CD4+ and CD8+ cells from the normal range. It is an open question whether the prognosis of the patients with normal positive rates of CD(4+)- and CD(8+)-activated lymphocytes is favorable or not.
Adult↗
Enhancing effect of pokeweed mitogen on the proliferation and the cytotoxicity of lymphokine-activated killer cells.
In order to obtain more potent lymphokine-activated killer (LAK) cells for use in adoptive immunotherapy, pokeweed mitogen (PWM) was added to the culture medium for the initial 24-48 h of culturing. The proliferation rate of PWM-stimulated LAK cells reached about 1000-fold after 3-week culture. This rate was nearly the same as that of LAK cells stimulated by 10 ng/ml of OKT3, the mouse anti-CD3 monoclonal antibody. However, the cytotoxicity of PWM-stimulated LAK cells was significantly more potent than that of OKT3-stimulated LAK cells. Phenotypic analysis revealed that PWM-stimulated LAK cells were CD3+CD56(+)-dominant while OKT3-stimulated LAK cells were CD3+CD56(-)-dominant. About half of CD3+CD56+ PWM-stimulated LAK cells was CD8+. These results suggest that more efficient adoptive immunotherapy is possible by using high-dose PWM-stimulated LAK cells with more potent cytotoxicity. Interleukin-1 beta and tumor necrosis factor alpha were significantly increased in the culture media after 24-h incubation with 1 micrograms/ml of PWM. Secretion of interferon-gamma was not enhanced by this concentration of PWM within 24 h. Therefore, PWM is considered to activate monocytes or macrophages to produce these cytokines in advance, influencing the proliferation and the cytotoxicity of LAK cells.
Antigens, CD↗
Topological localization of the frequency and amplitude characteristics of the whole and segmented renal pelvis.
The contractile characteristics of pacemaker regions in the unicalyceal renal pelvis of the rabbit were examined in vitro. The amplitude and frequency spectra of spontaneous contractions of whole and separated circular and longitudinal renal pelvic strips were identified. The effect of stretch on these parameters were examined in order to establish whether the pacemaker region that generates contractions in the renal pelvis was sensitive to distention. The results show that the frequency of spontaneous contractions in the whole pelvis (65 +/- 18 mHz) was significantly higher than any part of the circularly (41 x 8 mHz) or longitudinally cut (43 +/- 8 mHz) pelvis. The amplitude of longitudinal strips, 52 +/- 11 mg, was significantly smaller than that of the circular strips, 267 +/- 52 mg. In the circularly separated pelvis the frequency of spontaneous contractions was highest in the proximal part (41 +/- 8 mHz) and lowest in the pelviureteral junction (8 +/- 1 mHz). No significant increase in frequency was seen upon stretch in the whole or separated pelvis although there was a decrease in the amplitude of both the whole and separated pelvis. These results show that the frequency of contraction of the whole or the segmented renal pelvis is not sensitive to stretch.
Animals↗
Pokeweed mitogen induces p55 interleukin-2 receptor expression on human monocytes and its effect on interleukin-2 activated monocyte cytotoxicity.
Activation of human peripheral blood monocytes by pokeweed mitogen (PWM) results in the expression of interleukin 2 receptor(IL-2R) p55 chains, which are absent on resting monocytes. By dual-fluorescence flow cytometry, we found PWM induced detectable numbers of IL-2R+ cell which were further identified as LeuM3+ monocytes (22.91% of the LeuM3+ cells were IL-2R+ within 24h, and 32.17% in 48h). In addition, LPS can also induce IL-2R on 15.39% of LeuM3+ cells. On the contrary, other mitogens such as PHA or Con A, and cytokines as IFN-gamma, IL-2, M-CSF, TNF-alpha and IL-1 beta showed no influence on the IL-2R expression on monocytes. It was also noticed that PWM itself had no direct effect on HLA-DR antigen expression on LeuM3+ cells. The addition of IL-2 to PWM-pretreated IL-2R positive monocytes significantly augmented their tumoricidal activity. Thus monocytes when activated underwent a series of phenotypic and functional changes including the expression of IL-2R which may provide an important immunoregulatory pathway.
Cytotoxicity, Immunologic↗
Use of human leukocyte antigen-mismatched allogeneic lymphokine-activated killer cells and interleukin-2 in the adoptive immunotherapy of patients with malignancies.
Clinical effects and side effects were investigated in the adoptive immunotherapy of patients bearing malignant diseases using human leukocyte antigen (HLA)-mismatched allogeneic lymphokine-activated killer (LAK) cells. Allogeneic LAK cells were induced from peripheral blood lymphocytes (PBL) of healthy donors with the same blood types as those of patients. Recently we succeeded in increasing the proliferation rate and enhancing the cytotoxic activity of LAK cells by means of initial stimulation with pokeweed mitogen (PWM, PWM-LAK cells). Five of 12 patients applied in the adoptive immunotherapy showed clinical effects such as partial or complete regression of pulmonary metastases and pleural effusion. All pulmonary metastatic lesions were eliminated in one case by this adoptive immunotherapy combined with chemotherapy. Toxic effects were chillness, fever and general fatigue which were reversible, and no allergic side effects occurred even though allogeneic LAK cells were injected frequently. In the patients who received more than 10(11) of allogeneic LAK cells, anti-HLA class I antibodies appeared without any evidence of autoantibody. However, immunological side effects were never experienced after injection of allogeneic LAK cells even when the anti-HLA class I antibodies existed in the patients; this phenomenon suggests the safety of the adoptive immunotherapy using allogeneic LAK cells. Taken together, allogeneic LAK cells could be considered as alternative therapy for patients with malignancies who could not supply sufficient materials of autologous LAK cells. Recently, LAK cells, particularly PWM-LAK cells were found to obtain significantly potent and prompt lectin-dependent cell-mediated cytotoxicity (LDCC). All tumor cells confluent in microtest plate well could be annihilated by PWM-LAK cells plus PWM less than 8 hours. New immunotherapy using PWM-LAK cells or lectin-stimulated LAK cells with PWM or other lectins is discussed.
Adult↗
Endothelium dependent relaxation of human corpus cavernosum by bradykinin.
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Bradykinin↗
Relaxation mechanisms of antispasmodics papaverine and thiphenamil on the human corpus cavernosum.
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Diphenylacetic Acids↗
Biological activity in the human system of isotype variants of oligosaccharide-Y-specific murine monoclonal antibodies.
The capacity of isotype variants of BR55-2, an anti-tumor monoclonal antibody directed against Y oligosaccharide, to mediate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in the human system was evaluated using freshly isolated peripheral blood mononuclear cells, lymphocytes, monocytes and complement. The ADCC activities of the BR55-2 IgG3 isotype and its switch variants (IgG1, IgG2b, and IgG2a) with human monocytes were high for all isotypes, whereas the activity of all isotypes was lower with freshly isolated lymphocytes, IgG1 being the least effective. The CDC on the other hand was strong with IgG3, IgG2b and IgG2a and negative with the IgG1 variant. The IgG3 and IgG2a isotypes were selected for further development. Their strong ADCC and CDC activity against mammary carcinoma, colon carcinoma and small-cell lung tumor cell lines was confirmed quantitatively using proteins highly purified from tissue-culture supernatants. Significant variations in ADCC and CDC competence was observed among human donors.
Antibodies, Monoclonal↗
Regional effects of indomethacin, acetylsalicylic acid and SC-19220 on the contractility of rabbit renal pelvis (pacemaker regions and pelviureteric junction).
The effects of the cyclooxygenase inhibitors indomethacin and acetylsalicylic acid (ASA) and the prostaglandin (PG) antagonist 1-acetyl-2-[8-chloro-10,11-dihydrodibenz (b,f)(1,4) oxazepine-10-carbonyl]hydrazine (SC-19220) on smooth muscle strips from the rabbit renal pelvis were examined. Circularly oriented tissues were taken from within the renal pelvis and subdivided into the four adjoining regions, from fornix to pelviureteric junction (PUJ). They were set in a tissue bath and isometric tension changes were recorded. Spontaneous contractions were observed and electrical field stimulations evoked twitch-like contractions. The frequency of spontaneous contractions was dependent on the region within the renal pelvis from which they were dissected, gradually decreasing from fornix (3.92/min.) to PUJ (0.43/min.). Indomethacin (10(-5)M) or ASA (10(-4)M) significantly increased the frequencies of spontaneous contractions in all four regions. In the upper three regions (pacemaker regions), both agents significantly decreased the amplitudes of spontaneous and stimulation-induced contractions. In the PUJ region, both agents significantly increased the amplitudes of spontaneous and stimulation-induced contractions. SC-19220 (3 x 10(-5)M) significantly increased the frequencies and decreased amplitudes of spontaneous contractions in all four regions. These results suggest that the PUJ has different contractile characteristics from those of pacemaker regions and that decrease of amplitude by indomethacin or ASA is based on their cyclooxygenase inhibitor property.
Animals↗
Purification and characterization of aseanostatins: actinomycete-derived fatty acid inhibitors to myeloperoxidase release from human polymorphonuclear leukocytes.
We found inhibitors, designated aseanostatins P1 and P5, against myeloperoxidase (MPO) release from human polymorphonuclear leukocytes (PMN). Aseanostatins were extracted from an actinomycete isolated in Thailand and purified by a series of column chromatography of charcoal and silica gel, and HPLC. Physico-chemical characterization by gas liquid chromatography and GC-MS indicated that aseanostatins were fatty acids. The active forms of aseanostatins were recovered by hydrolyzing their methyl esters after HPLC. Two components P1 and P5 with the IC50 of 0.96 and 0.54 microgram/ml to the MPO release were obtained as pure forms, indicating aseanostatin P5 was higher activity than aseanostatin P1. The component P1 was identical with 12-methyltridecanoic acid and P5 was indistinguishable to 12-methyltetradecanoic acid (ante-i-15:0). Aseanostatin P5 (1 microgram/ml) did not inhibit beta-glucuronidase release, but O2- production a little. It has no effect on chemotaxis of PMN to fMet-Leu-Phe (10(-8)M), PMN adhesion or phosphorylation of a 64-kD protein in the PMN cell-lysate system.
Actinomycetales↗
Effects of [1-desamino-8-D-arginine]vasopressin and papaverine on rabbit renal pelvis.
The effects of [1-desamino-8-D-arginine]vasopressin (DDAVP) (V2 receptor agonist) and papaverine on four continuous circular smooth muscle strips in rabbit renal pelvis were studied by an isometric tension recording methods. DDAVP suppressed spontaneous contractions in a dose-dependent and region-dependent way. Papaverine suppressed these contractions in a dose-dependent way simultaneously in all four portions. These results suggest that there may be distribution differences of V2 receptors in the renal pelvis. Together with its anti-diuretic action, DDAVP may merit consideration for the treatment of renal colic.
Animals↗