Kijimicin: an inhibitor of human immunodeficiency virus in acutely and chronically infected cells.
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Biomedical subjects
Publications and source records attributed to T Ohno.
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Uterine cervical and corpus cancers have been reported to synthesize and secrete the putative peptide mitogen, which elicits a potent proliferative response in the fibroblasts [Res. Commun. Chem. Pathol. Pharmacol. 66, 477-480 (1989)]. The extract from human cervical cancers stimulated [H]thymidine incorporation into human endometrial fibroblasts in a dose-dependent manner. Concomitant exposure of the fibroblasts to dibutyryl cyclic AMP (cAMP) of forskolin, the mitogenic activity of the extract was suppressed by 60%. A higher concentration of the extract did not overcome the inhibitory effects of them, implying that they acted at a stage after the mitogen in extract and specific receptor interaction. These results demonstrated that the growth-promoting activity in cervical cancer extract could be under negative control through cAMP-dependent mechanism.
Thallium-201 planar and SPECT studies were performed in 38 children with congenital heart disease using high-resolution three-headed SPECT. The 201Tl total or average right ventricular-to-left ventricular (RV/LV) count ratios were measured by summed short-axis images. In the planar study, the RV/LV systolic pressure ratio correlated with 201Tl RV/LV average count ratio (r = 0.91) better than that in the SPECT study (r = 0.78). However, in the SPECT study, patients with atrial septal defect (n = 9), ventricular septal defect (n = 13), tetralogy of Fallot and double outlet right ventricle (n = 6) showed a characteristic distribution in the plot of RV/LV pressure ratio versus 201Tl RV/LV total count ratio. A prospective study showed that the RV/LV average count ratio was a good predictor of RV/LV pressure ratio (n = 19, r = 0.91). Three-headed SPECT is useful for pediatric cardiac studies, and the overload types found in congenital heart disease seemed to be differentiated by the SPECT study.
Meningioma includes some clinically malignant cases which grow multifocally or recur rapidly. To develop methodology to distinguish clinically malignant cases, we examined the nuclear DNA of meningiomas by flow cytometry using paraffin-embedded specimens. 52 surgical specimens were studied from 52 cases of meningioma. Among these cases, 3 multiple meningiomas that recurred multifocally within 3 years were included. Malignancy was assessed by the proliferative index (%S + %G2/M) and DNA ploidy of the specimens. Six cases were histologically malignant, while aneuploidy was observed in only 2 (33.3%). No significant correlation was observed when analyzing the 23.9% aneuploidy rate among benign cases. Moreover, three cases of clinically malignant meningiomas were all diploid. In contrast, the proliferative index of 19.82 +/- 9.45% among histologically malignant cases was significantly higher as compared to that for benign cases (11.50 +/- 5.49%). The proliferative index was 15% or more (average 22.02 +/- 6.01%) for patients with clinically malignant meningioma. This was considerably higher than the corresponding value for clinically benign meningiomas. Our analysis indicated that the assessment of benignancy or malignancy of meningioma on the basis of DNA ploidy alone is difficult. The proliferative index so obtained relates significantly to prognosis, apparently providing a useful prognostic assessment.
A 29-year-old man who had a taste for peanuts frequently showed abnormal behaviors. Physical examination revealed consciousness disturbance associated with flapping tremor, hypotonus in the extremities, and hypoactive deep tendon reflexes. Laboratory examination showed hyperammonemia with mild liver injury. A level of serum citrulline was 14 times higher than the upper limit of normal. A diagnosis of type 2 citrullinemia (Seheki et al) was established by the decreased argininosuccinate synthetase (ASS) in liver with low amount of ASS protein and normal kinetic properties. Diurnal fluctuation of consciousness level in this patient was not correlated with the concentration of ammonia in serum, but with that in cerebrospinal fluid. Main metabolic pathway of ammonia in brain is considered to be localized in astrocytes which have receptors for glucocorticoids. Glucocorticoids induce additional glutamine synthetase activity. Circadian rhythm of cortisol level might play a role in diurnal fluctuation of consciousness level in patients with citrullinemia.
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Fetal adrenal steroid, dehydroepiandrosterone sulfate (DHA-S) is well known to promote cervical ripening in late pregnancy. The presence of sites specifically binding the DHA-S in plasma membrane was studied in human cervical fibroblasts prepared from pregnant uterus. The fibroblasts were incubated with [3H] DHA-S and then fractionated into plasma membranes, cytosol, nuclei, and other organella debris. The specific activity of 3H-count in the plasma membrane fraction was enriched approximately 7-fold compared with the whole homogenate. When the isolated plasma membrane preparations from the fibroblasts were exposed to [3H] DHA-S, the binding showed saturation kinetics; an apparent equilibrium dissociation constant (Kd) of 12 nM, and the binding capacity (Bmax) of 1.25 pmol/mg protein. The present results suggest that DHA is bound to and recognized by components in plasma membrane, and may exert its action on cervical ripening through the membrane-mediated processes.
Synchronous double carcinoma of the lung and the esophagus is extremely rare disease. In Japan, 13 cases have reported by Abo and only 10 clinical cases have been documented so far. We describe two cases of synchronous double carcinoma of the lung and the esophagus. Case 1. A 74-year-old man was admitted to our hospital because of the abnormal shadow of the chest X-ray film. Left upper lobectomy was carried out for the lung carcinoma. Because of dysphagia after surgery, upper GI series and endoscopic biopsy were performed, and midesophageal carcinoma was revealed. Radical operation of the esophageal carcinoma was performed 2 months after the first operation. Pathological diagnosis of the lung tumor and the esophageal tumor were well differentiated adenocarcinoma and moderately differentiated squamous cell carcinoma respectively and both of them were early cancer. After 22 months of the second operation, he is doing well. Case 2. a 66-year-old man was operated on because of the esophageal carcinoma in other hospital. Abnormal shadow appeared in his X-ray film 10 months after operation. Although he received chemotherapy as metastatic lung cancer, bronchoscopic examination revealed it adenocarcinoma. We performed segmental lobectomy to him 17 months after the first operation. Pathological diagnosis was large cell carcinoma of the lung. He is also doing well 18 months after the second operation.
Recently it was suggested that the onset of sodium retention in experimental cirrhosis in rats is related to a critical threshold of hepatic function, as assessed by the aminopyrine breath test. The aim of this study was to evaluate whether sodium retention occurred after two-thirds hepatectomy in rats and to investigate the relationship between sodium retention and changes in hepatic function associated with liver regeneration in this model. Sodium balance, creatinine clearance, serum sodium and the aminopyrine rate constant of elimination were evaluated daily for 4 days after surgery in partially hepatectomized (n = 6) and sham-operated rats (n = 6). All rats in the partial hepatectomy group exhibited sodium retention (sodium balance greater than 0.7 mmol/day) 24 hr after surgery. This was associated with a 62% reduction of the aminopyrine rate constant of elimination. Spontaneous natriuresis which occurred between 2 and 4 days after surgery, was associated with an increase in the aminopyrine rate constant of elimination (from 0.73 +/- 0.02 x 10(-2) min-1 on the last day of sodium retention to 0.95 +/- 0.04 x 10(-2) min-1 on the first day of natriuresis [p less than 0.05]). In contrast, no change in creatinine clearance occurred over the same period. A negative curvilinear association was found between sodium balance and the aminopyrine rate constant of elimination in all animals (r = -0.72, p less than 0.001). These observations indicate that natriuresis is related to the recovery of liver function, not to changes in creatinine clearance. In conclusion, the concept of a critical threshold of liver function below which sodium retention occurs has been substantiated in this model of hepatic dysfunction.
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Silver-stained nucleolar proteins (AgNORs) were counted in a variety of bone tumors. In osteosarcomas, the number of AgNORs was also quantified before and after chemotherapy. Malignant bone tumor cells possessed more than five small AgNORs (5.85 +/- 1.39). Nuclei of benign bone tumor cells had less than three (2.61 +/- 0.51). A significant difference in the number of AgNORs between osteosarcomas before chemotherapy (6.10 +/- 1.22) and after chemotherapy (4.20 +/- 1.07) was observed. (p less than 0.001). The number of AgNORs in osteosarcoma patients with better prognoses was smaller than that of osteosarcoma patients showing poor prognoses, but without significant difference. The results of the present study indicate that the AgNOR count might help in determining malignancy, evaluating the effect of chemotherapy, and deciding the prognosis.
A 20-year-old man was admitted to our clinic with fever elevation up to 39 degrees C for two months, generalized lymphadenopathy and hepatosplenomegaly. Histological examination of right scalene lymph node with HE staining showed T cell lymphoma-like finding. The patient was given vindesine and prednisolone, and there was almost no clinical improvement. Abnormal large granular lymphocyte appeared in peripheral blood and increased up to 17,000/microliters in the terminal stage of clinical course. These lymphocytes had abundant pale cytoplasm with rich large azurophilic granules and a large nucleus with a few nucleoli. The phenotype of these cells were as follows: Fc gamma R+, CD2+, CD5-, CD7-, CD3-, CD4-, CD1-, CD8-, sIg-, CD20-, CD11-, CD13-, OKIa+, CD25-, CD16+, Leu7-. These cells did not have the activity of antibody dependent cellular cytotoxicity but had natural killer activity. The gene of T cell receptor (beta and gamma chain) did not rearranged in these cells. We concluded that the abnormal cells were derived from natural killer cells, which caused aggressive clinical course.
A case of syncytial variant of nodular sclerosing Hodgkin's disease in a 34-year-old woman is reported. Histologically, numerous Reed-Sternberg (RS) cells and their variants were seen in sheets. They were positive for CD30, CD15, CD25, and HLA-DR antigens. In addition, they expressed CD45 antigen and T-cell antigens (CD2, CD4). Molecular genetic analysis showed that this case had a germ line configuration for T-cell receptor (TCR) beta chain, TCR gamma chain, and immunoglobulin heavy chain genes. The percentage of the neoplastic cells in the specimen identified by CD30 positive cells was about 20% which was far above sensitivity of the molecular genetic analysis. Such analysis is reliable as to judgement of the results. Thus, these findings suggest that the RS cells and their variants in the present case are not derived from mature T cell in spite of their T-cell antigens expression.
Previous studies have demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) both increases and decreases levels of 3'-azido-3'-deoxythymidine (AZT) nucleotides in certain human myeloid cells. The present studies have examined the effects of GM-CSF on AZT metabolism in U-937 cells. The results demonstrate that GM-CSF stimulated AZT nucleotide formation in these cells. This stimulation was detectable during concurrent exposure to GM-CSF and AZT or as a result of pretreatment with GM-CSF. The GM-CSF-induced enhancement in AZT nucleotide formation was associated with a 4-fold increase in AZT uptake. The finding that uptake of AZT into U-937 cells was only partially sensitive to 6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine (NBMPR) suggested a process primarily involving nonfacilitated diffusion. The results also demonstrate that treatment of U-937 cells with GM-CSF was associated with nearly a 2-fold increase in thymidine kinase activity. Moreover, the findings indicate that retention of AZT-MP and AZP-TP was prolonged significantly (P less than 0.05 and P less than 0.01 respectively) in association with GM-CSF treatment. Taken together, these results suggest that GM-CSF enhances the formation of AZT nucleotides by increasing AZT uptake and phosphorylation, as well as increasing retention of phosphorylated derivatives.
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An IgM-binding protein of approximately 60 kD has been identified on activated B cells, but not on resting and activated T cells, monocytes, or granulocytes. Here, we characterize this IgM-binding protein as a receptor for the Fc portion (CH3 and/or CH4 domains) of IgM molecules (Fc microR). The Fc microR can be expressed as a cell surface activation antigen throughout the pre-B and B cell stages in differentiation. Receptor expression is not directly linked with IgM production, as both mu- pre-B cells and isotype-switched B cells may express the Fc microR. The receptor molecules produced by both pre-B and B cells are identical in size and are characterized as an acidic sialoglycoprotein with O-linked, but no N-linked, oligosaccharide. The Fc microR is anchored to the surface of B-lineage cells via a glycosyl phosphatidylinositol linkage. The Fc microR is thus the third member of a family of Fc receptors expressed on B-lineage cells, and its preferential expression on activated B cells suggests a potential role in the response to antigens.
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