Biomedical subjects
Publications and source records attributed to E Grand.
Steroidal glycoalkaloids of many Solanum species have recognized biological activities, especially those containing the glycosyl moiety alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-D-glucopyranose (chacotriose) whose peracetate is here synthesized and characterized by complete 1H and 13C NMR assignment.
Helicobacter pylori and proinflammatory cytokines have a direct stimulatory effect on gastrin release from isolated G cells, but little is known about the mechanism by which these factors regulate gastrin gene expression. We explored whether tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 directly regulate gastrin gene expression and, if so, by what mechanism. TNF-alpha and IL-1 significantly increased gastrin mRNA in canine G cells to 181 +/- 18% and 187 +/- 28% of control, respectively, after 24 h of treatment. TNF-alpha and IL-1 stimulated gastrin promoter activity to a maximal level of 285 +/- 12% and 415 +/- 26% of control. PD-98059 (a mitogen-activated protein kinase kinase inhibitor), SB-202190 (a p38 kinase inhibitor), and GF-109203 (a protein kinase C inhibitor) inhibited the stimulatory action of both cytokines on the gastrin promoter. In conclusion, both cytokines can directly regulate gastrin gene expression via a mitogen-activated protein kinase- and protein kinase C-dependent mechanism. These data suggest that TNF-alpha and IL-1 may play a direct role in Helicobacter pylori-induced hypergastrinemia.
Previously, we demonstrated that activation of the human H(2) receptor (hH(2)R) leads to an increase in c-fos transcription and cell proliferation. The purpose of these studies was to examine whether hH(2)R regulates c-jun expression and, if so, explore the mechanisms by which it does so. Histamine induced an increase in c-jun mRNA in human embryonic kidney cells stably transfected with the hH(2)R (maximal effect: 554.6 +/- 86.8% of control). The protein kinase C (PKC) inhibitors staurosporine (10(-6) M) and GF-109203X (10(-6) M) significantly inhibited histamine-stimulated c-fos mRNA while not altering c-jun expression. The protein kinase A (PKA) pathway inhibitors Rp-cAMP and protein kinase inhibitor did not affect the action of histamine on c-jun or c-fos mRNA. Histamine (10(-4) M) stimulated extracellularly regulated kinase 2 tyrosine phosphorylation. The specific inhibitor of the mitogen-activated protein (MAP) kinase pathway, PD-98059 (5 x 10(-5) M), significantly inhibited histamine-induced c-fos and c-jun mRNA. Of interest, the p70 S6 kinase inhibitor rapamycin (10(-6) M) but not wortmannin decreased histamine-stimulated c-jun mRNA by 58.5 +/- 12% (mean +/- SE, n = 4) while not significantly altering c-fos message. Histamine (10(-4) M) also led to an approximately 4.5-fold increase in Jun NH(2)-terminal kinase activity in a PKC-, PKA-, and MAP kinase-independent but rapamycin-sensitive manner. Our findings suggest that histamine stimulates both c-fos and c-jun mRNA in a differential manner. PKC is involved in histamine-mediated c-fos activation, whereas p70 S6 kinase is important for linkage of this receptor to c-jun.
A series of modified nucleosides bearing at varied positions of the sugar moiety one 3-aryl-1-triazeno N1-oxide group and a variable number of O-TBDMS groups have been prepared and their cytotoxicities and cytostaticities measured on different cell lines. Nucleosides bearing an aryltriazeno N-oxide group and O-TBDMS groups are either devoid of cytotoxicity or possess a selective cytotoxicity. On the other hand, nucleosides bearing one triazeno group and no silyl group are devoid of cytotoxicity and silylated nucleosides without triazeno group are generally either devoid of cytotoxicity or unselectively cytotoxic. This indicates that the O-TBDMS group per se is not cytotoxic.
C-disaccharide analogs of trehalose were prepared using an aqueous Diels-Alder reaction as a key step. The resulting major stereoisomer was shown by NMR spectroscopy analysis to have the correct (alpha, alpha') stereochemistry of trehalose.
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Nine cases of inflammatory invasive carcinoma of the uterine cervix are reviewed. All appeared in women under less than fifty years old, quickly after normal PAP smears. They occupied the endocervix, which mean diameter was 5 cm and outcome was very poor with only one survivor: four patients were free of disease in the pelvis and relapsed outside, the others underwent a local regional failure in less than 2 years. Association of radiotherapy and surgery is mandatory for stage IB and IIA FIGO; radiotherapy modalities--brachytherapy, external irradiation followed by brachytherapy--must be chosen according to tumor volume, size of the cervix, anatomy of vagina. For other stages radiotherapy alone is recommended using hyperfractionated treatment; in the future such observation would be documented by cytofluorometry analysis and/or molecular biology approach.
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Continuous measurement of the end-expiratory partial pressure of carbon dioxide (PETCO2) during anaesthesia has been proposed for non-invasive monitoring of arterial PCO2 (PaCO2). The values and the stability of the difference (PaCO2-PETCO2) during anaesthesia were studied for two ventilatory settings in eight children with healthy lungs and normal cardiac function undergoing minor surgery. PaCO2 values were all within a physiological range (30.2-43.6 mmHg). PaCO2-PETCO2 values ranged from 0.2 to 9.9 mmHg. With either mode of ventilation, there was no significant variation in PaCO2-PETCO2. It is concluded that estimation of PaCO2 was reliable during anaesthesia when haemodynamic and ventilatory states were stable, but a first determination of the PaCO2-PETCO2 gradient remained necessary for each child.
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Four types of bicyclonucleosides differing in the easiness of their ring-chain interconversion have been prepared, some exhibited anti-HIV activity and the ratio of their cyclic and open-chain forms could have some bearing on their biological activity.