[The critical period of experimental Arnold-Chiari type 1 malformation caused by mumps virus infection].
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Biomedical subjects
Publications and source records attributed to N Ono.
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The transposon Tn10-encoded tetracycline resistance protein functions as a metal-tetracycline/H+ antiporter (Yamaguchi, A., Udagawa, T., and Sawai, T. (1990) J. Biol. Chem. 265, 4809-4813). The Ser65-Asp66 dipeptide is conserved in all known tetracycline antiporter proteins and is an important target for site-directed mutagenesis. When Asp66 was replaced by Asn, the transport activity was completely lost, whereas when it was replaced by Glu, the activity was reduced to 10% of the wild-type level, indicating that a negative charge at position 66 is essential for tetracycline transport. Replacement of Ser65 by Cys or Ala, in contrast, caused only a minor change in tetracycline transport activity. However, the Cys65 mutant antiporter was sensitive to sulfhydryl reagents. Complete inactivation of the Cys65 antiporter by N-ethylmaleimide was not prevented by the substrate. A less bulky reagent, methyl methanethiosulfonate, caused partial inactivation of the Cys65 antiporter without changing its affinity to the substrate. These results indicate that a region including the dipeptide plays an important role in metal-tetracycline transport except for substrate binding. It may act as a gate which opens on the charge-charge interaction between Asp66 and the metal-tetracycline.
As a first step in the investigation of the reconstitution of steroid hormone receptor systems, we studied the reconstitution of 9 S estrogen receptor (ER) from purified vero ER, which is the estradiol binding subunit, and heat shock protein 90 (hsp 90). By using a phosphate buffer containing molybdate, thiocyanate, dimethylformamide, glycerol, etc., vero ER could be converted to 9 S ER with hsp 90, but not with the control protein, ovalbumin. Inactivation of ER during the reconstitution was suppressed partially by hsp 90, but not by ovalbumin. Like native 8 S ER, the reconstituted ER was sedimented at about 8.9 S and 4.6 S on glycerol gradient centrifugation in low and high salt buffers, respectively.
A mixed glioma and sarcoma in a 3-month-old infant is presented as a rare case of gliosarcoma with a good response to treatment. This congenital case is quite different from those in adults: the tumor cells were mainly composed of sarcomatous elements; glial components were not anaplastic without obvious endothelial hyperplasia, but presented as reticulin-free islands, mimicking a reactive glioma in a sarcoma. It may be termed "sarcoglioma" to distinguish from a classic gliosarcoma. The origin of the rare mixed tumor may be related to a dysgenesis of both mesenchymal and glial elements.
The prognosis of recurrent IV-ventricle ependymoma in children is poor. Three cases of recurrent ependymoma were treated with combination chemotherapy using cis-diamine dichloro platinum (II) (CDDP) and methyl-6-(3-(2-chloroethyl)-3-nitrosoureido)-6-deoxy-alpha-D-glucopyrano side (MCNU). The patients were 2-, 3-, and 6-year-old boys. The interval between the first operation with irradiation and recurrence was 1 year and 5 months to 2 years. Two cases showed a recurrence at the original site; in the other case, a right sylvian tumor deposit was found via computed tomography. The therapeutic regiment for recurrent ependymomas was as follows: (1) the tumor was debulked if possible; (2) additional local irradiation of 30 Gy was administered; (3) combined treatment of 100 mg/m2 CDDP and 80 mg/m2 MCNU over 24 h was given 5 times with an interval of 6 weeks between treatments. The patients tolerated the therapy well with only mild side effects. Remission lasted 1 year in two patients and has lasted for 8 months in one.
Lysis of virus-infected L929 target cells transfected with the H-2 class II IAk gene by class II-restricted influenza virus-specific murine cytotoxic T lymphocyte (CTL) clones was studied by electron microscopy and compared with lysis of L929 cells by class I-restricted CTL clones. T lymphocytes predominantly approached the basal surface of target cells grown on a plastic dish and also approached uninfected L929 target cells, although virus maturation exhibited no polarity with respect to the cell surface site. After incubation for 30 min, the target cell nuclei began to change: chromatin became irregularly redistributed and aggregated, and the nuclei appeared swollen. Later, electron-dense and -light areas of nuclei became segregated, and the cytoplasm became disorganized with many vacuoles. The ultrastructural changes of target cells during lysis by class I- and class II-restricted CTL clones appeared to be similar. These findings and other cytotoxicity data of class I and class II CTLs are discussed.
Pharmacological activities of mofezolac were investigated in experimental animal models and compared with those of indomethacin, ibuprofen, mefenamic acid, aspirin and aminopyrine. Mofezolac showed a potent suppression of various writhing models in mice or rats; and its potency was slightly lower than that of indomethacin, but was higher than those of the other reference drugs. Thus, mofezolac was especially active against chemically induced writhing and also in the phenylquinone induced intraperitoneal dye leakage reaction in mice. Mofezolac also has a potent inhibitory activity on the algesic responses induced by the mechanical stimulus of the inflammed tissue. Mofezolac exhibited a therapeutic effect comparable to indomethacin in the urate synovitis in dogs. Considering the anti-inflammatory and antipyretic actions, mofezolac was obviously less effective than indomethacin, and its potency was similar to that of ibuprofen. The ulcerogenic effect of mofezolac on the gastric mucosa was far weaker than that of indomethacin. In in vitro studies, the prostaglandin biosynthesis and platelet aggregation were inhibited to the same extent by both mofezolac and indomethacin. Accordingly, it may be considered that the actions of mofezolac are due to the inhibition of cyclooxygenase. Our result suggest that mofezolac can be a useful drug that shows a rapid pain-relieving activity in acute inflammations.
This study clarified the clinical profile and echocardiographic findings of severe idiopathic tricuspid regurgitation (TR). Among 8,538 consecutive ultrasonic examinations, a total of 63 patients had severe TR, which was depicted by color flow mapping as a regurgitant signal more than 4 cm from the tricuspid valve orifice. Thirteen of the 63 patients had no underlying diseases, and these patients with severe idiopathic TR were the subjects of the present study. All 13 patients were over 66 years of age (mean 77.3 +/- 5.6 years old) and had had episodes of right heart failure which responded effectively to diuretics. All 13 patients had atrial fibrillation. Using two-dimensional echocardiography, thickening (77%), prolapse (69%) and malaligned coaptation (54%) of the tricuspid valves were observed. The tricuspid annular diameters, cross-sectional areas of the right and left atria and the right ventricular end-diastolic dimensions were significantly greater than those of the age-and-gender-matched lone atrial fibrillation group and the normal control group (p less than 0.01). The left ventricular dimension and ejection fraction did not differ from those of the matched lone atrial fibrillation group. Other valvular regurgitations were also detected (AR 77%, MR 100%, PR 69%), but the degrees of regurgitation were minimal. We proposed severe TR with tricuspid annular dilatation, right atrial and right ventricular dilatation observed in the aged as a distinct cardiac disease entity.
Chemotherapy and chemoembolization using implantable infusion pump were performed in fifteen cases of hepatocellular carcinoma (HCC) and one case of cholangioma. The following results were obtained; (1) Complete response (CR) was obtained in two cases (12.5%) and partial response (PR) in three cases (18.8%) with HCC. (2) Tumor thrombus in the portal vein disappeared in two of four cases with HCC. (3) The followup period ranged from 54 to 768 days and administration from one to 33 times. These results suggest that good therapeutic effects and quality of life can be obtained by implantable drug delivery system.
Twenty-four adults with glioblastoma multiforme (astrocytoma, grade 4) underwent postoperative large dose fraction radiotherapy (LDFR; 5 Gy twice weekly) with Linac X-rays. The outcome in this group was compared with that of 26 patients who received conventional fractionated radiotherapy (CFR; 2 Gy 5 times weekly). The time, dose, and fractionation (TDF) factor was about 100 in both groups. The survival rates following LDFR and CFR were, respectively, 63% vs 65% at 1 year; 36% vs 8% at 2 years; 17% vs 4% at 3 years; and 4% vs 0% at 5 years. Although the survival curve for LDFR was superior to that for CFR, the difference was not statistically significant. Autopsies of nine LDFR and 13 CFR patients showed no residual tumor in one case and no cases, respectively; small residual tumor in three cases in each group; extensive coagulation necrosis of the tumor and surrounding brain tissue in one LDFR and four CFR patients; tumor proliferation in three LDFR and four CFR cases; and mixed glioblastoma and fibrosarcoma in one LDFR and two CFR patients. These results suggest that maximum tumor removal followed by LDFR may offer a better prognosis for patients with glioblastoma than that offered by surgery plus CFR.
Many investigators have reported the hemodynamics in acute cor pulmonale clinically and experimentally. However, earlier studies have not made quantitative evaluations of the effects of coronary perfusion pressure and hypoxia on right ventricular contractility. We simulated acute cor pulmonale in nine isolated canine hearts and investigated the relationship of the process to cardiac deterioration and restoration. The afterload and preload of the right ventricle were controlled with a computer-assisted load control servosystem. Coronary perfusion pressure (COPP) was also controlled at either normal or variable levels identical to products of measured cardiac output and assumed values of systemic vascular resistance. Critical state (CS) was defined as a condition with an initial decrease in peak systolic pressure despite increased afterload. Within the normal range of PaO2 (105 +/- 5.3 mmHg), CS developed at a COPP of 51 +/- 5.1 mmHg, while under low PaO2 (51 +/- 2.3 mmHg), it developed at a COPP of 59 +/- 8.8 mmHg. As long as the COPP was normal (90 mmHg), the contractility of the right ventricle did not decrease despite hypoxia (PaO2 51 +/- 2.3 mmHg). An increase in systemic vascular resistance or administration of a beta-stimulant at CS restored the contractility of the right ventricle. However, an increase in preload decreased the contractility of the right ventricle.
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The relationship between host immune state and hepatic inflammation and infection pattern of the Duck hepatitis B virus (DHBV) was investigated by experimental transmission of DHBV into 98 Japanese 7-day-old ducklings that had been pretreated with immunoregulatory drugs including cyclophosphamide, OK 432, and a steroid hormone. Immunosuppressive treatment with cyclophosphamide revealed an extension of the viremic period associated with an absence of inflammatory changes in the liver. Although immunostimulating treatment with OK 432 showed a remarkable accumulation of inflammatory cells in the liver, the viremic period was not shortened. Treatment with a steroid used as a immunosuppressant did not suppress the hepatitis; moreover, it increased viral DNA replication and extended the viremic period. This phenomenon of viral replication seemed to be caused by the direct effects of the steroid. Alteration of DHBV infection by modifying the host immune state is quite similar to that of hepatitis B virus (HBV) in humans. In DHBV infection, the host immune state seemed to have a considerable role in determining the infection pattern and degree of hepatitis activity. DHBV may be a helpful model of HBV for studying host-viral interaction and the immunological mechanism of viral hepatitis.
We have studied the histogenesis of malignant lymphoma (ML), small cleaved cell of the B-cell type and intermediate lymphocytic lymphoma (mantle zone lymphoma) by comparing immunophenotypes and ALP-activity of neoplastic cells with those of germinal center cells (follicular center cells) and mantle zone (MZ) cells of secondary follicles in non-neoplastic lymphoid tissues. The neoplastic cells in 3 cases of ML, follicular, small cleaved cell and 1 case of ML, small cleaved cell expressed the phenotypes similar to those of germinal center (GC) B lymphocytes (SIgM+, B1+, B2+, CALLA+, SigD-, IL-2R-, Leu-1- and ALP-). The neoplastic cells in 2 cases of ML, follicular, small cleaved cell and 12 cases of ML, diffuse, small cleaved cell displayed the characteristic phenotypes of MZ B lymphocytes (SIgM+, SIgD+, BA-1+, IL-2R+, Leu-1+ and ALP+). The phenotypes of 2 cases of mantle zone lymphoma were closely comparable with those of MZ B lymphocytes. These findings indicate that the histogenesis of ML, small cleaved cell of the B-cell type is heterogeneous and can be divided phenotypically into 2 types (GC B lymphocyte origin and MZ B lymphocyte origin). It is also apparent that intermediate lymphocytic lymphoma (mantle zone lymphoma) is derived from MZ B lymphocytes of secondary follicles.
Haloperidol given intraperitoneally dose-dependently elicited cataleptic behavior, evaluated by high bar and four-cork tests, in mice. The haloperidol-induced cataleptic behavior was reduced dose-dependently after oral treatment with aspirin, a cyclooxygenase inhibitor. The intra-cerebroventricular administration of prostaglandin F2a produced cataleptic behavior of long duration determined by the high bar test. It is suggested that prostaglandins may participate in the induction of cataleptic behavior in part.
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