Lack of effect of recombinant human interferon-alpha 2b on expression of 17-1A antigen on human colon cancer cells.

The effects of recombinant human interferon alpha (rHuIFN-alpha 2b) on cell growth, expression of antigenic receptor sites (r) and the affinity constant (Ka) of monoclonal antibody CO 17-1A IgG were studied on two human colorectal cancer cell lines, CX-1 and SW 1116. Cells were incubated with varying concentrations of rHuIFN-alpha 2b prior to exposure to 125I-labeled 17-1A IgG at 37 degrees C following which r and Ka were determined by means of Scatchard plots. Varying concentrations of rHuIFN-alpha 2b had significant growth inhibitory effects on CX-1 and SW 1116 cells, which were time and concentration dependent, but no effects on expression of r and Ka compared to controls. Our data indicate that rHuIFN-alpha 2b does not invariably increase the expression of tumor-associated antigens and that this effect may be independent of its antiproliferative activity. The in vitro response or lack thereof of neoplastic cells to rHuIFN-alpha 2b may be useful to identify those patients who potentially might gain from a clinical course of rHuIFN-alpha 2b for either therapeutic or diagnostic purposes.     

Hereditary protein C deficiency and portal-vein thrombosis

Inherited defects of the natural coagulation inhibitors predispose patients to thrombosis. These disorders have similar clinical presentations with a strong family history of thrombosis, episodes of recurrent venous thromboembolism, beginning in early adulthood. We report a case of upper gastrointestinal bleeding in a patient with portal hypertension due to portal-vein thrombosis secondary to hereditary protein C deficiency, an association that has seldom been reported.     

Effect of supplementation with water-soluble vitamins on erythrocyte alanine aminotransferase activity of healthy adolescents

The erythrocyte alanine aminotransferase (E-ALAT) activity with and without in vitro stimulation by pyridoxal phosphate of 60 healthy adolescents was measured before and after 6 weeks of supplementation with different water-soluble vitamins. The subjects who were divided into six groups received placebo (lactose tablets), pyridoxine, pyridoxine + ascorbic acid, pyridoxine + iron, pyridoxine + riboflavin and multivitamin supplements, respectively. Presupplementation E-ALAT activity increased significantly (p less than 0.05) for all supplemented subjects after 6 weeks. Deficient subjects (E-ALAT) index less than 1.16) however failed to respond to a combination of pyridoxine + ascorbic acid or multivitamins. It is suggested that pyridoxine in multivitamin preparations must exceed 1 mg to produce any useful improvement in vitamin B6 status of adolescents on suboptimal vitamin B6 intakes.     

Differences in metabolic activation of dibenzo[a,e]fluoranthene characterized by 32P-postlabeling in two mouse fibroblast models.

The formation of DNA adducts was investigated in mouse fibroblasts from two different tissues--embryos and adult lung--after incubation with dibenzo[a,e]fluoranthene (DBF) or its major proximate metabolites. The nuclease P1 modification of the 32P-postlabeling method was adapted for detection of DBF-DNA adducts. Quantitative and qualitative differences were observed in the metabolic activation mediated by the two cell types. DBF-DNA adducts generated three major spots reproducibly, and more than ten spots of medium or weak importance. The highest level of DNA binding occurred via the DBF-bay region vicinal dihydrodiol epoxide but with significant differences in the quantitative distribution of adducts. Striking qualitative differences were observed when lung fibroblasts were incubated with the DBF-pseudo bay region dihydrodiol (DBF-12,13-DHD). The spots representing adducts induced in embryo fibroblasts by DBF-3OH-12,13-DHD, a further metabolite of DBF-12,13-DHD, were totally absent from chromatograms of lung cells. These results show that both embryo and lung fibroblasts can activate DBF but that different cytochrome P-450 forms and substrate affinities are involved. The finding that different activation systems may be present in subcategories of the same tissue, may provide a partial explanation for the wide variations in sensitivity to carcinogens among species, organs and tissues.     

Dynamics of host blood effects inGlossina morsitans sspp. infected withTrypanosoma congolense andT. brucei

The pattern of infection inGlossina morsitans morsitans andG. m. centralis membrane-fed on eland, buffalo or goat blood mixed withTrypanosoma congolense orT. brucei was studied from day 1 to day 10. Tsetse were initially permissive vectors, with most flies harbouring infections of 10⁴–10⁵ parasites on day 3. However, after a second blood meal on day 3, flies cleared many infections withG. m. morsitans clearing more infections thanG. m. centralis. Infective feeds of goat blood consistently increased final infection rates by limiting the number of infections lost between days 3 and 6. In further experiments withG. m. morsitans only, this effect was replicated by feeding flies on erythrocytes but not on serum. These results suggest that compounds from some mammalian erythrocytes match the target specificity ofG. m. morsitans midgut lectins and, hence, have a protective effect on trypanosome establishment in the fly.     

MHC IN SYSTEMIC LUPUS ERYTHEMATOSUS: A STUDY ON A KUWAITI POPULATION

HLA alleles were studied in Kuwaiti patients with Systemic lupus erythematosus (SLE). Although significant association of B5, B8, and DR3 has been reported in the literature, the most common phenotype for our patients is A3, DR2 as susceptible alleles and DQ1 as a protective gene.     

Calcium Concentration-dependent Mechanisms through which Ketamine Relaxes Canine Airway Smooth Muscle

Background: Ketamine is a potent bronchodilator that, in clinically used concentrations, relaxes airway smooth muscle in part by a direct effect. This study explored the role of calcium concentration (Ca2+) in this relaxation.

Methods: Canine trachea smooth muscle strips were loaded with the fluorescent probe fura-2 and mounted in a spectrophotometric system to measure force and intracellular calcium concentration ([Ca2+]i) simultaneously. Calcium influx was estimated using a manganese quenching technique. Cyclic nucleotides in the airway smooth muscle strips were measured by radioimmunoassay.

Results: In smooth muscle strips stimulated with submaximal (0.1 micro Meter) and maximal (10 micro Meter) concentrations of acetylcholine, ketamine caused a concentration-dependent decrease in force and [Ca2+]i. The sensitivity of the force response to ketamine significantly decreased as the intensity of muscarinic receptor stimulation increased; the median effective concentration for relaxation induced by ketamine was 59 micro Meter and 850 micro Meter for tissue contracted by 0.1 micro Meter or 10 micro Meter acetylcholine, respectively (P < 0.05). In contrast, the sensitivity of the [Ca2+] sub i response did not depend on the intensity of muscarinic receptor stimulation. Ketamine at 1 mM significantly inhibited calcium influx. Ketamine did not significantly increase cyclic nucleotide concentrations.