Luminescence and defect formation in undensified and densified amorphous SiO2.
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Biomedical subjects
Publications and source records attributed to N Itoh.
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Twenty-eight evaluable patients with disseminated measurable malignancies of the genitourinary organs except testicular cancer were treated with MVP-CAB, between May 1985 and June 1988. Chemotherapy was given at 3 to 4 week intervals, as follows. On day 1, methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, and bleomycin 30 mg/body were administered. On day 2, cis-platinum 50 mg/m2, on day 1 to 3, prednisolone 20 mg/body were also administered. The administration of bleomycin and adriamycin were limited to 90 mg/body and 400 mg/m2. The median age was 59 years. The median follow-up duration was 11 months. The primary lesions were urothelial tract cancer (19 patients), malignant lymphoma (1 patient), renal cell adenocarcinoma, penile cancer, prostatic adenocarcinoma, and leiomyosarcoma (2 patients each). CR was observed in 2 patients, and PR in 11 patients with urothelial tract cancer. The overall response rate was 68% (13/19). The response rates in primary and metastatic lesions were 56% (5/9) in primary, 73% (8/11) in lymph node, 71% (5/7) in lung, 67% (2/3) in liver, and 20% (1/5) in bone. The median duration of survival in the responders was 13.5 months, and in the non-responders was 5 months. The 1 year survival rate by Kaplan-Meier method was 70% in responders. On the other hand, the longest survival time in non-responders was 9 months. Marked improvement of survival time was noted in the responders. PR was observed in 1 patient with malignant lymphoma, prostatic adenocarcinoma, and leiomyosarcoma in each. The main toxic effect of MVP-CAB was bone marrow suppression. Leucopenia (WBC less than 4,000/mm3) was noted in 24 patients (86%), and 16 patients (57%) had a WBC count nadir below 2,000/mm3. Thrombocytopenia (plt less than 10 x 10(4)/mm3) was noted in 10 patients (36%). However, there were no deaths due to the bone marrow suppression.
Interleukin-3 (IL-3) binds to its receptor with high and low affinities, induces tyrosine phosphorylation, and promotes the proliferation and differentiation of hematopoietic cells. A binding component of the IL-3 receptor was cloned. Fibroblasts transfected with the complementary DNA bound IL-3 with a low affinity [dissociation constant (Kd) of 17.9 +/- 3.6 nM]. No consensus sequence for a tyrosine kinase was present in the cytoplasmic domain. Thus, additional components are required for a functional high affinity IL-3 receptor. A sequence comparison of the IL-3 receptor with other cytokine receptors (erythropoietin, IL-4, IL-6, and the beta chain IL-2 receptor) revealed a common motif of a distinct receptor gene family.
We attempted to examine the immunopathological change of the pancreatic islets of newly diagnosed Type 1 (insulin-dependent) diabetic patients and thereby to obtain useful information for the therapy of the patients. For this purpose, pancreas biopsy under laparoscopy was performed 2-4 months after the onset of Type 1 diabetes in seven newly diagnosed patients. All biopsies were performed safely without any complications. Immunohistochemical examination of the biopsy specimens revealed a marked decrease of insulin-containing cells, preservation of glucagon-containing cells, and various degrees of expression of MHC class I and class II antigens in islet cells and in endothelial cells within and around the islets. Signs of active autoimmune phenomena, e.g. lymphocytic infiltration or immunoglobulin deposition in islets, were not detected in any of these patients by light microscopical evaluation. We conclude that pancreas biopsy under laparoscopy has shown various immunological changes in the islets of newly diagnosed Type 1 diabetic patients. Pancreas biopsy, however, may not be suitable under the present protocol for the selection of patients for immunotherapy because of problems including sampling errors.
We investigated the effect of an immunosuppressant FK-506 on histological change of islets, the onset of diabetes, and the change of spleen cell subsets in female non-obese diabetic mice. Mice administered intraperitoneally with FK-506 from 5 to 20 weeks of age showed marked suppression of mononuclear cell infiltration (insulitis) at 10 weeks of age. Among the subsets of the spleen cells, a significant decrease in the population of Thyl.2-positive T cells (pan-T), L3T4-positive T cells (mainly helper/inducer), and Lyt2-positive T cells (mainly suppressor/cytotoxic) was observed in FK-506-treated mice. Furthermore, glucose tolerance of the mice at 15 weeks of age was clearly improved. Cumulative incidence observed up to 40 weeks of age was 86% in control mice and 23% in FK-506-treated mice (p less than 0.01). These data indicate that FK-506 has a preventive effect on insulitis and diabetes by the suppression of cell-mediated autoimmunity in non-obese diabetic mice.
An increase in microfilaments in phalloidin-treated hepatocytes of Wistar rats was identified three-dimensionally with myosin subfragment 1 (S1) on replica membranes, using the quick-freezing and deep-etching method. Almost all of the reticular microfilaments around the bile canaliculi and beneath the lateral cell membranes were decorated on their surfaces by S1 attachment. Some showed periodic structures. However, thinner filaments with diameters of 4-7 nm were not decorated by S1. Bundled intermediate filaments around the bile canalicular microfilaments and intermediate filaments localized among cell organelles had smooth surfaces without S1 decoration. The microfilaments decorated by S1 were attached directly to bundled intermediate filaments. The quick-freezing and deep-etching method is useful in analysing cytoskeletal pathology and can be applied to histochemical fields.
Immunological studies on psoriasis have been done using monoclonal antibodies (MoAbs) to elucidate the relation between gamma-interferon (IFN-gamma) secreted from inflammatory infiltrate, and the expression of HLA-DR molecule on epidermal keratinocytes in the lesion. In highly inflamed psoriatic lesions, IFN-gamma producing cells were found in the inflammatory infiltrate of the dermal papillae, while keratinocytes located near IFN-gamma+ cells expressed HLA-DR molecules on the surface. In fully developed psoriatic lesions, HLA-DR+ keratinocytes were mainly found in the thin epidermis over the elongated dermal papillae where IFN-gamma deposited not only at infiltrates but also in teh dermal components. The IFN-gamma+ cells were activated T cells which exhibited HLA-DR and interleukin 2 receptor. Munro's microabscess under the horny layer also included IFN-gamma producing cells. A radioimmunoassay by the sandwich method with anti-human IFN-gamma and anti-recombinant IFN-gamma MoAbs found that extracts from psoriatic scales contained IFN-gamma. The results suggest that HLA-DR+ keratinocytes are due to the effect of IFN-gamma secreted by activated T cells in psoriatic lesions. The proliferation of keratinocytes over the dermal papillae in fully developed lesions seemed to be inhibited by IFN-gamma from the inflammatory infiltrate. We consider that cell-mediated immune reaction plays an important role in the development of psoriatic eruption.
Using a monoclonal antibody to the interleukin 3 (IL-3) receptor (anti-Aic2), we isolated a cDNA (AIC2B) from a mouse mast cell line which is homologous to the previously characterized gene for the IL-3 receptor (AIC2A). This cDNA encodes a polypeptide of 896 amino acid residues and has 91% amino acid sequence identity with the IL-3 receptor. A consensus sequence defining an additional cytokine receptor family is present in this clone. Compared to the AIC2A clone, the AIC2B cDNA encodes a protein with amino acid substitutions, insertions, and deletions dispersed throughout the entire protein. Oligonucleotide probes specific for each cDNA hybridized with different genomic fragments, indicating that the AIC2A and AIC2B proteins are encoded by two distinct genes. Fibroblasts transfected with the AIC2B cDNA expressed the protein at the cell surface as determined by binding with the anti-Aic2 antibody but did not bind IL-3 or other cytokines, including IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, erythropoietin, and IL-9 (p40) at concentrations between 1 and 10 nM. An S1 nuclease protection assay was used to discriminate between the AIC2A and AIC2B transcripts. We found that the AIC2B gene was coexpressed with the AIC2A gene. These results suggest a potential involvement of AIC2B in cytokine signal transduction.
Interleukin 4 (IL-4) is a potent mediator of growth and differentiation for various lymphoid and myeloid cells. To isolate a cDNA encoding the murine IL-4 receptor, we have developed an expression cloning method that uses biotinylated ligand as a probe and that may be generally applicable to cloning of receptor genes. COS-7 cells transiently transfected with the cloned full-length cDNA bind murine IL-4 specifically with a Kd = 165 pM. Crosslinking of 125I-labeled IL-4 to COS-7 cells transfected with the cDNA reveals binding to proteins of 120-140 kDa. IL-4-responsive cells also express IL-4-binding proteins of 120-140 kDa but show additional bands at 60-70 kDa; the relationship of the smaller proteins to the larger ones is unclear. The nucleotide sequence indicates that the full-length cDNA encodes 810 amino acids including the signal sequence. While no consensus sequence for protein kinases is present in the cytoplasmic domain, a sequence comparison with the erythropoietin receptor, the IL-6 receptor, and the beta chain of the IL-2 receptor reveals a significant homology in the extracellular domain, indicating that the IL-4 receptor is a member of a cytokine receptor family.
Rat liver mannan-binding protein (R-L-MBP) is a lectin specific for mannose and N-acetylglucosamine. Northern blot hybridization analysis with a R-L-MBP cDNA (0.9 kb), which we isolated previously [Oka, S., Itoh, N., Kawasaki, T., & Yamashina, I. (1987) J. Biochem. 101, 135-144], revealed that R-L-MBP was encoded by two species of mRNA of 1.4 and 3.5 kb long, respectively. Analysis of a newly isolated cDNA clone of 3.3 kb long showed that the sequence of the open reading frame of the 3.5 kb mRNA was completely identical to that of the 1.4 kb mRNA. The 3'-untranslated region of the 3.5 kb mRNA contained two inverted copies of the previously described identifier (ID) sequence, which is a repetitive element of the rat genome [Milner, R.J., Bloom, F.E., Lai, C., Lerner, R.A., & Sutcliffe, J.G. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 713-717]. Southern blot analysis of rat genomic DNA digested with restriction enzymes suggested that each mRNA species arises from one gene, with the differences in size most easily being accounted for by differential utilization of the polyadenylation sites of one transcript.
The effects of estradiol (E2), progesterone (P), and danazol on the production of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) by OK-432 (a streptococcal preparation)-stimulated monocytes were examined. E2 and P at physiologic concentrations enhanced IL-1 beta and TNF production by monocytes from donors with lower control levels (without steroids added) of IL-1 beta and TNF. However, E2 and P at physiologic concentrations did not affect IL-1 beta and TNF production by monocytes from donors with higher control levels of IL-1 beta and TNF. Danazol inhibited IL-1 beta and TNF production by monocytes in a dose-dependent manner from not only donors with lower control levels of IL-1 beta and TNF but also donors with higher control levels of IL-1 beta and TNF. Danazol at a concentration of 10(-6) M significantly suppressed IL-1 beta and TNF production in the presence of E2 and/or P at concentrations giving peak responses of IL-1 beta production. These findings suggest possible new mechanisms of action for danazol in the treatment of endometriosis and infertility associated with immune abnormalities.
We measured the amount of antibodies to a synthetic peptide that corresponds to the alpha-subunit residues Lys125-Thr148 of human acetylcholine receptor (AChR) in myasthenic sera. We detected anti-peptide antibodies in 52% (89/171) of the patients with myasthenia gravis (MG), but none in any of the healthy controls. Anti-peptide antibodies should provide a valuable immunologic parameter for the clinical evaluation of MG, but no apparent correlation was observed between the titers of anti-peptide and anti-AChR antibodies.
A low molecular weight protein was separated from urine samples obtained from a heifer with spontaneous renal disease and from cows with CaNa2EDTA-induced renal dysfunction. The molecular weight and electrophoretic mobility of the separated protein were examined. The low molecular weight protein collected by gel filtration chromatography was further separated into two fractions by ion exchange chromatography using DEAE-cellulose. One of the two fractions, the lowest molecular weight protein showed a single band in SDS-PAGE, and its molecular weight was approximately 12,000. An antiserum against this protein formed a single precipitin line with the urine from cows with experimentally induced renal dysfunction and a heifer with spontaneous renal disease by the double immunodiffusion technique. However, the antiserum did not form any precipitin line with the concentrated urine of healthy cow and human beta 2-microglobulin. In cellulose acetate membrane electrophoresis, this protein migrated in the same position as that of serum gamma-globulin from healthy cow.
This study was designed to evaluate the functional changes of Sertoli cells following the administration of clomiphene citrate for male infertility. Sperm count and seminal transferrin level were measured before and after the treatment in 22 cases of oligozoospermia (sperm count: less than 20 X 10(6)/ml) and 14 cases of subnormal sperm count group (sperm count: 20-30 X 10(6)/ml). Clomiphene citrate was administered per os for more than 3 months consecutively in a dose of 25 mg/day. Seminal transferrin concentration increased more than 1.5 times compared with pre-treatment level in 6 cases (16.7%). Among these patients, sperm count markedly increased (20 X 10(6)/ml or more than the pre-treatment level) in 3 cases (50%) and slightly increased (10 X 10(6)/ml or more than pre-treatment) in 1 case (16.7%). In 30 cases, in which seminal transferrin level did not increase, sperm count markedly increased in 6 cases (20%) and slightly increased in 6 cases (20%). Thus, sperm count was improved more frequently in the cases in which seminal transferrin level remained elevated than the cases with no elevation of serum transferrin level. Serum FSH level of patients whose seminal transferrin level remained elevated after the treatment was significantly higher than that of patients with no elevation of serum transferrin level (mean +/- SD = 32.8 +/- 18.0 mIU/ml v.s. 14.4 +/- 11.7 mIU/ml, respectively). These data suggested that the activation of Sertoli cells may contribute to the increase of sperm count following the administration of clomiphene citrate and the elevated seminal transferrin secretion may be related to the increase of serum FSH level following this treatment.
We examined sera from 113 patients with myasthenia gravis (MG). Most of the patients with ocular MG without thymoma and 15% of the patients with generalized MG had immunoprecipitation (IP) titers of anti-acetylcholine receptor (anti-AChR) antibodies within the normal range for healthy subjects. We developed a highly sensitive radioassay using Staphylococcus aureus cells, and re-examined the 86 serum samples that had negative titers by IP. Using the radioassay, we detected anti-AChR antibodies in 27 (31%) of these myasthenic sera, of which 19 were from ocular MG patients without thymoma. By combining the standard IP assay and our new radioassay, we increased to 50% the overall percent positivity of detecting nonblocking-type antibodies in ocular MG patients without thymoma. We detected no anti-AChR antibodies in nearly all patients with various immunological and neurological diseases other than MG, and in all the healthy controls. The data for these sera indicate that in some cases the standard IP assay gives false-negative reactions. Thus, use of the more sensitive radioassay is preferable for accuracy.
Status asthmatics is characterized pathologically by bronchial smooth muscle spasm, and mucous plugging of the small airways. Clinically, it is characterized by the disturbance of gas exchange. In severe cases, unresponsive to standard therapy (including oxygen, epinephrine, aminophylline and steroids, artificial ventilation, tracheobronchial lavage and inhalation), anesthetic therapy should be started without delay. Inhalation anesthetics, halothane or ether, have potent bronchodilating properties which facilitate the removal of mucous plugging. We reported nine cases with status asthmatics treated by inhalation anesthetic therapy. Halothane (0.5-3.0%) was used in all cases, ether (1.5-3.0 ml/kg) was used in five cases. The duration of anesthesia was 0.5 to 13.5 hours. In three halothane anesthesia cases, blood pressure was reduced before there was improvement in wheezing, so we were forced to change halothane to ether. In all cases, the symptoms of status asthmatics were improved, but two patients died due to other complications. We recommended the following method, viz that halothane be administered at first, and be changed to ether in order to maintain circulatory movement.
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