[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
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Journal Article↗
Biomedical subjects
Y Tao
Publications and source records attributed to Y Tao.
Nitric oxide-releasing compounds inhibit Dictyostelium discoideum aggregation without altering cGMP production.
The effects of nitric oxide-releasing compounds on Dictyostelium discoideum cell development and guanylyl cyclase activity were studied. The addition of SNP (sodium nitroprusside) or SIN-1 (3-morpholino-syndnonimine) to starved cells inhibited their differentiation and aggregation in a concentration-dependent manner. In contrast to mammalian systems, SNP did not significantly affect guanylyl cyclase activity in cell lysates of D. discoideum, nor did it stimulate cGMP production in intact cells. The results suggest that the inhibitory effects of NO on D. discoideum cell aggregation are through a mechanism independent of an effect on guanylyl cyclase activity.
Animals↗
Comparison of spontaneous motor pattern generation in non-hemisected and hemisected mouse spinal cord.
Spontaneous electromyogram (EMG) patterns in the gastrocnemius (G) and tibialis anterior (TA) muscles of spinal cord-hindlimb explants from neonatal mice were investigated. Compared to non-hemisected explants, neither longitudinal hemisection of the spinal cord nor hemisection plus transection at L1 significantly altered the incidence of spontaneous motor rhythm. Therefore, not only does each half of the neonatal spinal cord contain sufficient circuitry to generate motor rhythm, but the more reduced preparations were just as likely to produce such activity. Hemisected preparations, however, exhibited slower rhythm, perhaps due to the loss of excitatory commissural connections. No correlation was found between the number of cycles in a rhythmic sequence and cycle period. In hemisected as well as non-hemisected explants, sequences of spontaneous EMG rhythm occurred in either the G or TA muscle, but not in both muscles simultaneously. Consequently, cycle-to-cycle alternation between rhythmic bursting in the G and TA muscles was not observed. The excitability in such preparations was apparently insufficient for maintained activations of both muscles (either for cycle-to-cycle alternation or for co-contraction).
Animals↗
Nitric oxide stimulates the ADP-ribosylation of a 41-kDa cytosolic protein in Dictyostelium discoideum.
Nitric oxide-releasing compounds were shown to activate an ADP-ribosyltransferase activity in the cytosol of Dictyostelium discoideum. The enzyme ADP-ribosylated a cytosolic protein of approximately 41 kDa, p41. Neither cGMP nor GTP and its analogues affected this ADP-ribosylation. p41 differs from other substrates ADP-ribosylated by cholera, pertussis, or diphtheria toxins. Treatment of ADP-ribosylated p41 with snake venom phosphodiesterase released adenosine 5'-monophosphate, indicating a mono-ADP-ribose-protein linkage. This linkage was stable to neutral hydroxylamine but was sensitive to mercury ions and iodomethane, suggesting an attachment to a cysteine residue. Treatment of intact cells with nitric oxide-releasing compounds appeared to stimulate the ADP-ribosylation of p41 and this modification was reversible.
ADP Ribose Transferases↗
Guinea pig model of immunologic asthma induced by inhalation of trimellitic anhydride.
We established a model of asthma induced by trimellitic anhydride (TMA) in guinea pigs and assessed the role of sensitization in the development of their bronchial hyperresponsiveness, and relationship between bronchial responsiveness and bronchial inflammation. Fourteen guinea pigs (sensitized group) were administered 1 mg/0.5 ml of trimellity 36-bovine serum albumin intramuscularly and 0.5 ml of complete Freund adjuvant on Day 1 as the priming dose. Booster doses were repeated on Day 15. By Day 28, all of the sensitized animals showed a high passive hemagglutination titer against trimellityl 14-ovalbumin. On Day 29, they were challenged by an inhalation of TMA (150 mg/m3) for 30 min, and respiratory resistance (Rrs) was monitored by the oscillation method. In all sensitized animals, Rrs increased immediately upon challenge and returned to baseline within 6 h. The bronchial reactivity to acetylcholine (Ach), measured 6 h after TMA challenge in the sensitized animals, increased significantly (p < 0.01) compared with that measured 24 h before challenge; that measured 24 h later was not different from that before challenge. There was also a significant difference (p < 0.01) in the number of eosinophils in the lamina propria and the epithelium 6 and 24 h after the challenge inhalation in the sensitized group. The increased airway responsiveness to Ach in the sensitized animals was correlated with an increase in the number of eosinophils in the lamina propria and the epithelium. These observations suggest that humoral antibody and eosinophils are involved in the pathogenesis of TMA-induced asthma.
Acetylcholine↗
Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies.
PURPOSE: Intrapleural cisplatin-based chemotherapy has been used in the treatment of patients with malignant pleural mesothelioma and malignant pleural effusions, but the pharmacokinetics of this form of chemotherapy have not been previously evaluated. We performed pharmacokinetic studies on 12 patients who received both intrapleural cisplatin and mitomycin immediately following pleurectomy/decortication for malignant pleural mesothelioma. PATIENTS AND METHODS: Simultaneous pleural fluid and plasma samples were collected at 15 and 30 minutes, and at 1, 2, 3, 4, and 24 hours after administration of the intrapleural chemotherapy (cisplatin 100 mg/m2 and mitomycin 8 mg/m2), and after cisplatin (total and free) and mitomycin levels were measured. The mean peak levels, the areas under the concentration-time curve (AUC) and the drug half-lives (t1/2s) in plasma and pleural fluid were compared using the paired t test. Differences were considered significant if P less than or equal to .05. RESULTS: Systemic absorption was rapid, with peak plasma levels being reached within 1 hour of administration of the intrapleural chemotherapy. Peak plasma levels measured after intrapleural chemotherapy approximated those reportedly attained during systemic administration of these drugs at similar doses. However, the mean peak cisplatin and mitomycin levels, and their mean AUCs, were significantly higher in the pleural fluid than in the plasma. There was a three- to fivefold advantage (on a logarithmic scale) for pleural to plasma AUCs for both cisplatin and mitomycin. The mean t1/2s for cisplatin and mitomycin were significantly longer in the plasma than in the pleural fluid. CONCLUSIONS: The pharmacokinetics of intrapleural cisplatin-based chemotherapy are analogous to those of intraperitoneal chemotherapy. Our findings show that intrapleural cisplatin-based chemotherapy has a distinct local pharmacologic advantage, but also produces significant and sustained drug plasma levels.
Antineoplastic Combined Chemotherapy Protocols↗
[Erythema multiforme caused by the combination of carbamazepine and cerebral irradiation].
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Brain Neoplasms↗
[A quantitative analysis of pulmonary arterioles in 402 cases of cor pulmonale].
A quantitative analysis of pulmonary arterioles were made in 402 cases of cor pulmonale. The results showed that arteriole muscularization and medial hypertrophy, intimal fibrosis of pulmonary small arteries were important lesions. The authors found that right ventricular hypertrophy was bound to follow intimal fibrosis of pulmonary small arteries but was not along with medial hypertrophy and arteriole muscularization, and that the lesion of pulmonary arteries was not balanced with the course of disease. The authors considered that these results were related to vessel dilatation and medial atrophy because of intimal pressure in late stage of the disease.
Adolescent↗
[A case of small cell carcinoma of the lung with carcinomatous lymphangiosis-like shadow].
A 60-year-old man was admitted to our hospital on January 29, 1991 with dry cough, shortness of breath on exertion, appetite loss and abnormal shadows on chest X-ray. Chest X-ray on admission showed marked vascular shadows in both lung fields accompanied by left interlobar effusion. Chest CT showed thickening of vessels and bronchial walls with prominent interlobular septa in the subpleural regions. These findings suggested that the lesions were located in the peribronchial and perivascular interstitium and interlobular septa. Biopsy specimens of bronchial epithelium, lung tissue and right supraclavicular lymph nodes revealed small cell carcinoma (intermediate cell type). Because of the absence of lesions in other organs, the initial diagnosis was carcinomatous lymphangiosis of small cell carcinoma of the lung. However, the mild symptoms, normal arterial blood gas and good response to chemotherapy suggested the possibility of extensive small cell carcinoma of longitudinal spread type. Although small cell carcinoma of the lung is not a rare disease, this case suggests two possibilities. 1) Carcinomatous lymphangiosis of small cell carcinoma may have different symptoms, clinical course and prognosis from that of non-small cell carcinoma. 2) Carcinomatous lymphangiosis of small cell carcinoma may not be a clinical entity and in fact may simply represent extensive small cell carcinoma of longitudinal spread type.
Carcinoma, Small Cell↗
Cytogenetic analysis of 434 consecutively ascertained specimens of non-Hodgkin's lymphoma: clinical correlations.
Cytogenetic and histopathologic data were correlated with clinical parameters from 423 patients with non-Hodgkin's lymphoma (NHL). Clinical correlations were performed on subgroups of 149 patients with low-grade lymphoma (LG) and 205 patients with diffuse lymphoma with a large cell component (DLLC). Correlations were made between clinical outcome and individual recurring cytogenetic aberrations, each of which was noted in greater than 5% of cases belonging to LG NHL and DLLC, and derived measures of karyotypic complexity, comprising modal chromosome number, number of marker chromosomes, and number of translocation breakpoints. No correlations with survival were noted in LG NHL, although median follow-up was only 2 years. Seven patients with t(8;14) LG NHL had an indolent course. Among 104 patients with DLLC and abnormal karyotypes at diagnosis, breaks at 1q21-23 or more than 4 marker chromosomes was associated with a shortened median survival. Using these variables we constructed a proportional hazards model with a good fit to observed data. Breaks at 6q21-25 predicted a decreased probability of achieving remission. Patients with DLLC and breaks at 1q21-23 or 1p32-36 had a shorter duration of complete remission. Of 41 DLLC studied at relapse, the only long-term survivors had t(14;18).
Analysis of Variance↗
Basis for natural resistance to methotrexate in human acute non-lymphocytic leukemia.
The basis of intrinsic resistance of blasts from patients with acute non-lymphocytic leukemia (ANLL) to methotrexate was studied. MTX polyglutamate formation was measured in blast cells from 19 patients with ANLL and in 7 pediatric patients with acute lymphocytic leukemia (ALL), after in vitro incubation for 24 h with 3H-methotrexate. There was no significant differences seen in the total amount of MTX plus polyglutamates measured between ANLL and ALL blasts, indicating that transport defects do not account for intrinsic MTX resistance in ANLL. However, there were significant differences between the amounts of long chain MTX polyglutamates found in ANLL cells as compared to ALL cells. Most, but not all, ANLL blasts were unable to form long chain polyglutamates. In as much as the level of MTX polyglutamates found in blast cells after MTX administration allows for retention of this drug, this property may explain, at least in part, the refractoriness of most patients with ANLL to methotrexate.
Adolescent↗
Experimental lung injury induced by trimellitic anhydride inhalation on guinea pigs.
Trimellitic anhydride (TMA) causes lung injury by inhalation exposure in humans. In order to investigate more precisely the mechanism of lung injury by TMA, an experimental animal model of TMA-induced lung injury was established. Guinea pigs were intramuscularly injected with trimellitylated bovine serum albumin (TM BSA) with complete Freund's adjuvant (CFA). Appreciable amounts of antibodies against TM epitopes were detected in the sera of these animals. Guinea pigs that were passively sensitized with anti-TM antisera as well as the actively immunized animals developed hemorrhagic pneumonitis after TMA inhalation. It is well recognized that hyperimmune antisera of guinea pigs contain two subclasses of IgG antibodies, IgG1 and IgG2, which are known as homocytotropic and heterocytotropic antibodies, respectively. To determine the role of these antibodies in the airway injury with alveolar hemorrhages, they were isolated by gel filtration and by ion exchange column chromatography, and the guinea pigs that were sensitized with each of these antibodies were exposed to TMA inhalation. The extent of lung injury in these animals was quantitatively determined by the measurements of lung extravasation of Evans blue dye injected intravenously after TMA inhalation. Significant increases in the extravasation of dye were observed in both animal groups sensitized with IgG1 and IgG2 antibodies. In addition, results obtained with heat-treated antisera and IgG1 antibody did not significantly differ from those obtained with untreated samples. These results suggest that the lung injury resulting from TMA inhalation exposure can be induced with humoral antibodies, not only IgG1 but also IgG2, and that at least two types of allergic reactions are involved in the pathogenesis of lung injury.
Alveolitis, Extrinsic Allergic↗
[Common tumors of the fourth ventricle and cerebellum in childhood: evaluation of CT differential diagnosis].
Forty pediatric patients with infratentorial cerebellar astrocytomas, medulloblastomas and ependymomas were evaluated. In most cases it was possible to predict the histological type of these tumors by CT. The search for the residual fourth ventricle cavity and defining its location were the first step in differential diagnosis. The density of tumor on plain scans was of value to distinguish medulloblastomas from astrocytomas. Cerebellar astrocytomas had an obvious tendency to develop cystic change. Especially, the configuration of "Cyst-with-mural nodule" was the most specific characteristic in diagnosis. Just like medulloblastomas and ependymomas, cerebellar astrocytomas may have also the tendency to arise at the midline in childhood. The incidence of calcification was rather high in ependymomas.
Adolescent↗
[Post-transfusion hepatitis in operated uterine cancer patients].
We examined the incidence of non-A, non-B hepatitis (NANB) in post-transfusion hepatitis in uterine cancer patients treated by surgery at our hospital. The diagnosis of NANB was based on the diagnostic standards for post-transfusion hepatitis of the Japanese Society of Gastroenterology 1985. In 587 patients with blood transfusions from 1978 to 1988, 80 patients (13.6%) were diagnosed as NANB. The proportions of blood components were, preserved whole blood 44.1%, concentrated red blood cells (CRBC)+ fresh frozen plasma 31.2%, and CRBC 12.8%. The proportions of blood components changed over the years, but since 1987 those of blood components in blood transfusion have been greatly decreased. No difference in the incidence of NANB was seen in patients with up to 10 units of blood transfused, but a high incidence was observed to patients who had received over 10 units. The number of patients treated by radical hysterectomy was five hundred and sixty-two (95.7%) out of a total of five hundred and eighty seven. The average blood loss in the operation was 1,392 ml.
Female↗
[Screening of beta-N-acetylhexosaminidase forming strains and conditions for enzyme production].
About 1200 strains of microorganisms were screened including fungi, actinomyces, and bacteria, in which 237 strains producing the enzyme desired. The results showed that the beta-GlcNAcase and beta-GalNAcase always co-existed in one strain, though may be in different ratio. From strains mentioned above the authors screened out a potent beta-N-acetylhexosaminidase producing strain, Aspergillus tamarii S215, from the soil sample. The optimal conditions for enzyme production were as follows: the microorganisms was inoculated in a 5% wheat bran suspension, cultured at 28-30 degrees C on shaker for 5-6 days. The productivity can be moderately enhanced by the addition of cellobiose or glucosamine or galactosamine or by the extra supplement of (NH4)2SO4 and NH4NO3 as N sources. In the culture filtrate of Asp. tamarii, the alpha, (beta)-galactosidase, beta-glucosidase, alpha-mannosidase and beta-fucosidase were also found.
Aspergillus↗
[Purification and characterization of beta-N-acetyl hexosaminidase from Aspergillus tamarii].
A beta-N-acetylhexosaminidase from mycelium-free culture filtrate of Asp tamarii S215 was purified to PAGE homogenous by ammonium sulfate and polyethylene glycol fractionation precipitation followed by Sephadex G-50 desalt, DEAE-Sephadex A-25 chromatography, hydroxyapatite chromatography and DEAE-Sephadex A-25 rechromatography with 170-fold purification and 24.7% recovery. The ratio of the beta-GlcNAcase and beta-GalNAcase was 2.5 and remained constant throughout the purification. The Mr estimated with concentration gradient PAGE was 140,000 and subunit Mr determined with SDS-PAGE was 72,000, the number of subunit were 2. The pI was 4.2 determined by PAGIEF. The optimum pH was 5.5-6.5 and 5.0-6.0 for beta-GlcNAcase and beta-GalNAcase respectively with stable pH range 5.5-8.3 for both. The optimum temperature was 60 degrees C for beta-GlcNAcase and beta-GalNAcase. The residual activity of beta-GlcNAcase was 52.7% after treated at 50 degrees C for 8 h and it was 44.9% for beta-GalNAcase. The residual activities of both were down to 1% after treated at 62 degrees C for 10 min. The activity was slightly activated by Mn2+ or Fe2+, while strongly inhibited by Hg2+ and slightly by Ag+, Cu2+, Pb2+, Cd2+ or Zn2+. Analyses of amino acids composition showed that the beta-HexNAcase contained about 24.2% acidic amino acids and 14.9% basic amino acids and only 0.6% methionine.
Acetylglucosaminidase↗
[The marrow granulocyte reserve in lung cancer patients].
The marrow granulocyte reserve (MGR) of patients with lung cancer have been estimated by measuring the maximum neutrophil increment after administration of hydrocortisone. The MGR was found to have decreased in four of 19 untreated patients, but the reason for this decrement was not clear. Further, there were no differences in the MGR between the cell types or cancer stages. The MGR in patients 70 years old or older tended to be decreased. After chemotherapy or radiation therapy, the MGR depressed significantly. However, on administration of OK 432, the MGR significantly increased in two patients who had received radiation therapy and whose MGR had been deficient initially.
Adult↗
[A case of ovarian germ cell tumor].
PVP (CDDP, VBL, PEP) regimens were administered to a case of ovarian embryonal carcinoma (Higuchi-Kato) Group C, which had metastatic lesions of liver, lumbar bones, and paraaortic lymph nodes soon after operation, with good results.
Adolescent↗