Synthesis and antiviral activity of sulfonamidobenzophenone oximes and sulfonamidobenzamides

To find antiviral agents, various sulfonamidobenzophenone oximes (II) were synthesized from the appropriate m-sulfonamidobenzophenones by hydroxylamine reaction. The reaction products were generally obtained as syn/anti mixtures which were separable by fractional crystallization. The anti isomer had more potent antipoliovirus activity than the syn isomer. Various sulfonamidobenzamides (III) which were structurally related to II were synthesized by the reactions of amino-substituted benzamides with sulfuryl chloride or amines with (aminosulfonyl)benzoyl chloride. Antiviral activity was examined by the plaque-inhibition test. Compounds 5, 36, and 69 exhibited strong antipicornavirus activity. The structure-activity relationships are discussed.     

Experimental evaluation of respiratory assist and hemodynamic changes by veno-venous bypass

The veno-venous bypass (VVB) with a membrane lung is one of the effective procedures to provide respiratory assistance even in patients with a high mortality rate when assisted only with mechanical ventilation. The purpose of this experimental study was to reveal the efficacy of respiratory assistance and the hemodynamic changes by VVB in acute respiratory failure. VVB was carried out in 22 mongrel dogs with acute respiratory failure induced by intratracheal seawater infusion. The ventilation-perfusion ratio (V/Q) of a membrane lung was changed to 1.0, 2.0 and 3.0 for each of the bypass flow rates of 20%, 40%, 60% and 80% of pre-perfusion cardiac output. For each condition variables indicating blood gas status and hemodynamic parameters were measured. As the indicator evaluating the efficiency of CO2 removal by VVB, the index of VVBCO2R was used, indicating the blood CO2 tension differences between IVC and the pulmonary artery. Arterial oxygen saturation was increased with bypass flow rates greater than 60% compared with pre-VVB, but the change was not marked. VVB was considered to be inadequate as a method of oxygenation. Besides, oxygenation was not able to be controlled by changing V/Q. However, significant reduction of arterial CO2 tension (PaCO2) could be obtained even with a bypass flow rate of 20%. As the blood flow rate increased, PaCO2 was lowered. But no more significant reductions of PaCO2 were obtained even with the flow rate of 60% and 80%. VVBCO2R was increased by changing the bypass flow rate from 20% to 40%, while no further increases were observed even with changes from 40% to 60% and 80%.(ABSTRACT TRUNCATED AT 250 WORDS)     

HLA phenotype in patients with osteosarcoma

Nineteen patients with typical osteosarcoma were studied for evidence of association with human leukocyte antigen (HLA) phenotypes. HLA-A11 was detected in nine of 19 patients (47.4%) compared with 16.9% of 235 controls (chi 2 " 10.861, p less than 0.001), which yielded an odds ratio of 4.523. The positive rate of HLA-A11 was significantly increased in the patients. Interestingly, five of seven patients with poor prognosis had HLA-A11, compared with two of nine disease-free patients, 18 months after the initial treatment. These data suggest that major histocompatibility complex (MHC)-linked genes determines susceptibility to the occurrence of osteosarcoma and its prognosis.     

Transient induction of single GST-P positive hepatocytes by DEN

The single cells positive for placental glutathione S-transferase(GST-P), detectable in livers of rats soon after treatment withhepatocarcinogens, are possible ‘initiated cells’,the hypothesis tested in the present series of experiments.No low dose threshold was observed in male Sprague-Dawley ratsat different single doses of diethylnitrosamine (DEM) althougha plateau was reached between 160 and 200 mg/kg body weight.At the latter single dose 12 400 positive cells/cm³ were observedimmunohistochemically in rat livers after one week, the numbersthen decreasing to week 8 and thereafter rising again. In thenumbers then decreasing to week 8 and thereafter rising again.In the early stages single cells predominated but with timea gradual increase in mini-foci and larger lesions became evident.Application of selection pressure (feeding of diet containing0.02% 2-AAF plus partial hepatectomy) to rats 2–24 weeksafter single DEN-treatment resulted in the formation of largefoci positive for GST-P, especially in the early stages, thegrowth response being less pronounced with time. The numberof foci, on the other hand. was correlated with the number offoci, on the other hand, was correlated with the number ofsingle cells/mini-foci detected inhepatectomy tissue of thesame individuals. These results suggest that the early GST-Ppositive populations could be the precursor for preneoplasticfoci and nodules.     

Diazepam reduces both arterial blood pressure and muscle sympathetic nerve activity in human

It is known that benzodiazepines have a hypotensive effect, but the mechanism has not been well elucidated yet. To clarify whether this effect is due to central or peripheral mechanism, we administered 5 mg of diazepam or saline intravenously to healthy volunteers and assessed the change in blood pressure, heart rate, muscle sympathetic nerve activity and heart rate variability. After diazepam administration, systolic and mean blood pressure decreased significantly. Muscle sympathetic nerve activity was also significantly reduced but heart rate did not change, whereas the variables of spectral analysis of heart rate variability did not show significant change. We concluded that the hypotensive effect of diazepam in human is mainly due to the central mechanism.     

Presence of natural killer-cell clones with variable proliferative capacity in chronic active Epstein-Barr virus infection

Chronic active Epstein-Barr virus infection (CAEBV) is a syndrome that takes diverse clinical courses and is often associated with lymphoproliferative disorders of T/natural killer (NK)-cell lineage. We describe a patient with CAEBV associated with persistent pharyngeal ulcer, and with subsequent nasal T/NK-cell lymphoma in her neck lymph nodes and nasopharynx. Immunophenotyping of lymphoid cells showed that the lineage of Epstein-Barr virus (EBV)-positive cells in the patient was of NK-cell origin. By means of high-dose recombinant interleukin-2, we established an EBV-positive cell line of NK-cell lineage from her peripheral blood. Southern blot analysis for the number of terminal repeat sequences of EBV detected three NK-cell clones in the patient's lymph node. One of these clones was identical to the established cell line but was not observed in the pharyngeal ulcer, while the other two clones were present in the pharyngeal ulcer. These results suggest that the patient had expansion of the three NK-cell clones, one of which had proliferative capacity in vitro and was involved in the formation of the lymphoma. Moreover, the results suggest that the proliferative capacity of EBV-positive cells can be variable even in a single patient, and this variability may explain the clinical diversity in CAEBV.     

Relationship between production of epidermal growth factor receptors, gene amplification, and chromosome 7 translocation in variant A431 cells

Synthesis of the epidermal growth factor (EGF) receptor has been analyzed in a series of variant A431 human epidermoid carcinoma cell clones reported to contain different amounts of EGF binding sites. The amount of EGF receptor protein, quantitated by immunoaffinity chromatography, and EGF receptor mRNA, quantitated by cDNA hybridization, were closely correlated to the extent of EGF receptor gene amplification. This correlation existed in variants selected for reduced EGF receptors and in revertants from those variants with increased EGF receptors. There was also a correlation between the frequency of translocation of chromosome 7, containing the EGF receptor gene, and EGF receptor protein. These results support gene amplification as the mechanism enhancing A431 cell EGF receptor protein and determining growth responses.