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Biomedical subjects

M Ali

Publications and source records attributed to M Ali.

At least 361 records · Page 20Linked to original sources

The involvement of prostaglandins and thromboxanes in the response to pulmonary embolism in anaesthetized rabbits and isolated perfused lungs.

Embolisation of blood clots produced an increased pulmonary artery pressure in vitro and systemic hypotension in vivo. In control anaesthetized animals, systemic blood pressure fell by 44.9 +/- 28.0 mm Hg following embolisation and 40% of the animals died within 5 minutes of embolisation. Plasma concentrations of thromboxane B2 (TXB222222 2) and 6-keto-prostaglandin F 1 alpha (6-keto-PGF 1 alpha) were increased by 0.54 +/- 0.13 ng/ml and 0.41 +/- 0.25 ng/ml, respectively. Pretreatment of animals with aspirin (ASA), 5 mg/kg or 250 mg/kg, reduced the hypotensive response and the TXB 2 and 6-keto-PGF 1 alpha release. Embolisation of isolated lungs perfused with blood-free medium induced an increase in pulmonary artery pressure of 32.7 +/- 21.0 mm Hg and significantly increased the content of TXB 2 and 6-keto-PGF 1 alpha in the perfusate. Pretreatment of lungs with indomethacin, 10 micrograms/ml, reduced the mean pulmonary pressure response to embolisation to 10.6 +/- 4.9 mm Hg and blocked the appearance of TXB 2 in the perfusate. Embolisation with an agarose clot induced only a 2.58 +/- 0.8 mm Hg increase in pressure and no detectable TXB 2 release. These results indicate that embolisation of lungs with a blood clot induces the release of TXB 2 and 6-keto-PGF 1 alpha. The release of these mediators, the hemodynamic responses and mortality were blocked by ASA pretreatment.

6-Ketoprostaglandin F1 alpha↗

Identification and origin of oestradiol-binding protein in immature rat skin. Demonstration of oestrophilic alpha-foetoprotein synthesis and secretion by developing rat skin explants in culture.

Oestrophilic alpha-foetoprotein (alpha FP) is found in high concentrations in developing rat skin cytosol. Elevated levels of alpha FP observed in foetal-rat skin decreased during development, and the protein became undetectable after 3 weeks of postnatal life. The developmental profile of alpha FP in skin is different from that in foetal blood. alpha FP in skin arises as a result of its synthesis in situ in the epidermal cells. Synthesis of alpha FP in skin is demonstrated by linear incorporation of [14C]leucine into immunoprecipitable, intracellular alpha FP by skin explants during 6 h in culture. Secretion is demonstrated by incorporation into alpha FP in culture medium. The rate of alpha FP synthesis in skin also declined with age and its synthesis is completely switched off 2 weeks after birth. The skin alpha FP level during development is regulated by controlling the rate of its synthesis in skin. alpha FP synthesized and secreted by skin is immunologically, electrophoretically and, with respect to molecular weight and oestradiol-binding properties, similar to that found in foetal serum. alpha FP was also identified as the major oestradiol-binding protein present in newborn-rat skin or secreted by newborn-rat skin explants in culture.

Animals↗

Interference following dual inoculation with influenza A (H3N2) and (H1N1) viruses in ferrets and volunteers.

The effects of simultaneous inoculation with two attenuated influenza A viruses was studied in ferrets and volunteers. Groups of ferrets were inoculated with an influenza A (H3N2) or (H1N1), virus or a combination of both viruses: the temperature response, serum and local antibody response, and the change in nasal wash protein concentration was determined. The results showed that both viruses were attenuated for ferrets, and that inoculation with both viruses together did not cause clinical reactions. Serological studies on paired serum samples obtained from ferrets showed that both viruses when given separately infected all the inoculated animals; however, dual infection resulted in all ferrets being infected with the influenza A (H3N2) virus strain, but this infection interfered with infection by the influenza A (H1N1) strain. Similar investigations were carried out in volunteers. Again, the clinical reactions and temperature response of volunteers to infection by one or other of the viruses showed both strains to be attenuated for man even when given together. In addition, no adverse clinical reactions were seen in volunteers inoculated with both viruses simultaneously. Serum antibody studies showed that infection by influenza A (H1N1) virus interfered with infection by the influenza A (H2N2) virus strain. These results show evidence of interference by influenza A viruses; however, the direction of interference was one-way, and differed for ferrets and for volunteers.

Animals↗

Changes in alpha-fetoprotein and albumin synthesis rates and their levels during fetal and neonatal development of rat brain.

An attempt was made to find a correlation between AFP and albumin levels in brain and their rates of synthesis in the brain cells during maturation of rat brain. Levels of alpha-fetoprotein (AFP) and albumin in the developing brain were studied by rocket immunoassay. Rate of synthesis of AFP and albumin in brain cell cultures, established from rat brain at various stages of development, were determined by incorporation of [14C]leucine into immuno-precipitable intracellular AFP and albumin. AFP and albumin levels in brain as well as rates of their synthesis by brain cells in culture registered a continuous decline during development. Synthesis of AFP and albumin in the brain is switched off after first week of postnatal life with a concomitant disappearance of these proteins from the brain. Levels of AFP and albumin in brain correlated well with rates of their synthesis by brain cells in vitro at any specific stage of brain maturation implying that levels of AFP and albumin in brain are regulated by controlling rates of their synthesis in the maturing brain cells.

Age Factors↗

In vivo and in vitro hamster models in the assessment of virulence of recombinant influenza viruses.

The virulence of five wild-type influenza A viruses and 14 recombinant viruses, prepared from the cold adapted A/Ann Arbor/6/60 virus and various wild-type viruses, was studied by two methods. Firstly, the viruses were inoculated into hamsters, and the titres present in the lungs and turbinates at 1, 3 and 4 days post-infection were measured. Secondly, the effect of five wild-type and ten recombinant viruses on the ciliated epithelium of in vitro hamster tracheal organ cultures was examined. The results obtained were assessed with reference to the known virulence of the viruses for human volunteers. The results showed that virus strains virulent for man grew to higher titres in hamster lungs and turbinates than attenuated strains; and that virulent strains destroyed the ciliary activity of hamster tracheal organ cultures more quickly and to a greater extent than attenuated strains. Comparison of the results with the known virulence of viruses tested for man suggests that the reduced ability of virus to grow in hamster lung tissue and the relatively little effect on ciliary activity may be used as markers of virus attenuation; however, the growth of virus in hamster turbinates overlaps for virulent and attenuated strains and therefore was not considered a useful marker of virulence.

Animals↗

Sensitivity of rabbit platelet and aortic cyclooxygenase to inhibition by aspirin.

It has been suggested that aspirin (ASA) would be more effective as an antithrombotic agent if employed in a dose which inhibits platelet thromboxane synthesis selectively, sparing vascular synthesis of prostaglandin I2 (PGI2). We have studied the effect of ASA concentration on rabbit platelet and aortic cyclooxygenase activity in vitro and the effect of administration of varying doses of ASA to rabbits on the cyclooxygenase activity of these tissues ex vivo. We also measured plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) after infusion of arachidonic acid into rabbits pretreated with varying doses of ASA. Concentrations or doses of ASA required for 50% inhibition were about 10 times greater for the arterial enzyme than for the platelet enzyme in the in vitro and ex vivo studies. However, the dose required for complete inhibition of the platelet enzyme was 1 mg/kg and this dose inhibited the vascular enzyme by 62%. We conclude that meaningful selective inhibition of cyclooxygenase activity of the two tissues is difficult to achieve in the rabbit. Since doses of ASA which are antithrombotic appear to be high enough to almost totally inhibit vascular PGI2 synthesis, PGI2 synthesis may be a relatively unimportant mechanism for prevention of thrombosis.

6-Ketoprostaglandin F1 alpha↗

Recovery of cyclooxygenase activity after aspirin in populations of platelets separated on stractan density gradients.

Human platelets obtained before and at intervals up to one week following the ingestion of 650 mg acetylsalicylic acid (ASA) were subjected to fractionation on discontinuous gradients of stractan. Platelets were recovered from the density gradients and incubated with arachidonate. Thromboxane synthesis was estimated by radioimmunoassay (RIA). There were no differences in cyclooxygenase activity among the platelet fractions prior to ASA ingestion. ASA inhibited synthesis of thromboxane B2 (TXB2) by 98% in all subfractions. Twenty-four hours after ASA ingestion the total platelet population exhibited 10% of the control cyclooxygenase activity suggesting that new platelets emerging from the bone marrow within 24 hours of an ASA dose have functional cyclooxygenase enzymes. The pattern of return of TXB2 synthesis differed markedly among the platelet fractions, indicating differences in the distribution of new platelets among these fractions. New platelets with functional cyclooxygenase enzyme were twice as concentrated in the less dense fractions as in the most dense fraction. By 72 hours up to 75% of the platelets in the less dense fractions synthesized thromboxanes, while only 27% of platelets in the most dense fraction were active. Newly formed platelets may increase in density as they age or platelets of low density have a more rapid turnover than platelets of high density.

Aspirin↗

Effects of ASA on thromboxane and prostacyclin synthesis by rabbit aorta and pulmonary artery.

Rabbit aorta and pulmonary artery were incubated in the presence and absence of added arachidonic acid, and the synthesis of prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) was studied by radioimmunoassay of the stable hydrolysis products 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2). Aorta and pulmonary artery synthesized 6-keto-PGF1 alpha and TXB2 in ratios of 10-60:1. The pulmonary artery appeared to synthesize relatively more thromboxane. This may be because of a thinner muscular layer, since smooth muscle cells have previously been shown to produce only 6-keto-PGF1 alpha, while endothelial cells synthesize both compounds. Pretreatment of animals with aspirin (ASA) in a dose of 1 mg/kg strongly inhibited synthesis of both products by aorta and pulmonary artery. A dose of 0.1 mg/kg was without effect. After a single intravenous dose of ASA, the inhibitory effect was maximal between 4 and 12 hours and was still marked at 24 hours, increasing to normal at approximately 48 hours. Selective suppression of platelet cyclooxygenase activity with sparing of the vascular enzyme appears to be difficult to achieve.

6-Ketoprostaglandin F1 alpha↗

Harmonic analysis of ultradian respiratory rhythms in four small laboratory vertebrates lit in LD12:12.

Fourier harmonic analysis has been applied to 20-min samples of VCO2, recorded every 12 sec over several (7-12) days, in one mouse, one rat, one guinea-pig, or one quail, maintained in controlled conditions of temperature, humidity and ventilation, and lit in LD12:12 (100 lux). The harmonic computations, during L and D of ultradian periods (1.2 hr less than tau less than 12 hr) evidence statistically significant differences in amplitude and phase between these four small laboratory species. These periodic respiratory differences correspond to discrepancies in their diurnal and nocturnal activities, and in their responses to light and dark.

Animals↗

Pattern of liver disease in the western region of Saudi Arabia.

In a series of 124 patients admitted to hospital with liver disease, 23 (18.6%) had malignant liver disease, either primary or secondary; 12 (9.7%) had cirrhosis of the liver, while another 25 (20.2%) had inflammatory liver disease, including such parasitic infections as hydatid disease and schistosomiasis. The remaining biopsies showed non-specific changes or normal livers.

Adolescent↗

Serum concentrations of allergen-specific IgG antibodies in inhalant allergy: effect of specific immunotherapy.

The occurrence of antibodies belonging to IgG class of immunoglobulins with specificity for short ragweed and Bermuda grass in the sera of nonatopic subjects and patients with inhalant allergy (at the time of initial diagnosis, following specific immunotherapy was investigated with an enzyme immunoassay. The intra-assay and inter-assay coefficients of variation for this assay ranged from 1.74%-4.62% and 3.18%-9.12%, respectively. IgG antibodies were found in the sera of the majority of nonatopic and all of atopic subjects. The differences in the concentration of these antibodies between these three groups were statistically significant (P less than 0.001). Specific immunotherapy resulted in a rise in the serum levels of allergen-specific IgG antibodies and, following an initial period of modest increase, a decrease in the level of allergen-specific IgE antibodies. Specific IgG response correlated with both the cumulative antigen dose and the clinical benefit that accrued from specific immunotherapy (P less than 0.001). The increase in the serum concentration of specific IgG was most pronounced in patients with high RAST scores at the time of initial diagnosis (P less than 0.001). The concentrations of short-ragweed specific IgG antibodies assayed with multiple samples in three patients with ragweed hay fever appeared not to be affected by the short-ragweed season to any significant degree. We conclude that direct enzyme immunoassay for allergen-specific IgE and IgG antibodies are useful in vitro monitors of immunologic responses to specific immunotherapy for inhalant allergy.

Allergens↗

Regulation of cytotoxic reactivity to minor histocompatibility antigens by administration of Corynebacterium parvum.

B10.BR(H-2k) mice were primed with H-2-identical allogeneic CBA/J(H-2k) spleen cells and restimulated in vitro 14 days later to generate specific secondary cytotoxic lymphocytes. A single intravenous injection of primed mice with 700 micrograms of Corynebacterium parvum 7 days after alloimmunization markedly inhibited the subsequent secondary in vitro generation of cytotoxic cells. In addition, regulatory spleen cells were detected in alloimmunized C-parvum-injected mice that prevented the restimulation of primed control spleen cells. Suppressive activity could not be abrogated by treating regulatory cells with anti-theta antibody and complement or by removing phagocytic cells, but it was overcome by treatment with mitomycin C. Unfractionated regulatory cells suppressed responses in an antigen nonspecific fashion. However, cells remaining after carbonyl and iron treatment (nonphagocytic) could no longer suppress responses to third party alloantigens while maintaining significant suppression of anti-CBA responses. These data suggest the generation of two distinct suppressor cell types that can control the cytotoxic response to minor histocompatibility antigens: an antigen-nonspecific phagocytic cell and an antigen specific nonphagocytic, non-theta-bearing cell.

Adjuvants, Immunologic↗

Isolation, characterization, and synthesis of alpha-fetoprotein from neonatal rat brain.

Monospecific anti-rat serum alpha-fetoprotein (AFP) IgG was coupled to cyanogen bromide-activated Sepharose-4B (4.5 mg/ml packed volume of gel) to yield an immunoaffinity matrix. The immunoaffinity column was used to isolate AFP from feto-neonatal rat brain. The purified AFP was immunologically and electrophoretically similar to serum AFP. It yielded a single band with a molecular weight of 70,000 on sodium dodecyl sulphate polyacrylamide gel electrophoresis. Polyacrylamide gel electrophoresis of the protein under nondenaturing conditions yielded two charge variants of AFP, reminiscent of AFP from feto-neonatal rat serum. The AFP was observed to bind estradiol with Ka = 5.8 X 10(8) M -1 and 1.3 X 10(8) M -1 by dextran-coated charcoal adsorption and Sephadex gel filtration techniques, respectively. Newborn rat brain cells linearly incorporated [14C]leucine into immunoprecipitable AFP during 6 h in culture. It is, therefore, concluded that feto-neonatal rat brain contains AFP similar to that present in fetal serum and that it may arise in brain as a result of its in situ synthesis.

Animals↗

Thromboxane synthesis by sources other than platelets in association with complement-induced pulmonary leukostasis and pulmonary hypertension in sheep.

Infusion into sheep of plasma containing zymosan-activated complement produces leukopenia, pulmonary leukostasis, and pulmonary artery hypertension. We previously demonstrated a close relationship between the pulmonary vascular response and elevations of plasma thromboxane. We have investigated the source of thromboxane synthesis in this model. Plasma containing zymosan-activated complement added to whole blood did not stimulate thromboxane synthesis. This observation suggested that leukocytes do not synthesize thromboxane directly in response to complement added to whole blood did not stimulate thromboxane synthesis. This observation suggested that leukocytes do not synthesize thromboxane directly in response to complement. Sheep rendered severely thrombocytopenic by the administration of antiplatelet serum responded to complement infusion in the usual way. Pretreatment with aspirin (10 mg/kg) protected sheep against the pulmonary vascular response and completely blocked thromboxane synthesis. Transfusion of functional platelets did not restore these responses. Twenty-four hours after aspirin treatment, in vivo thromboxane synthesis was significantly greater than platelet thromboxane synthesis in vitro. Thromboxane is synthesized by a tissue which recovers cyclooxygenase enzyme activity at a rate that is more rapid than platelet turnover. Sheep lung synthesizes thromboxane actively in vitro. It is postulated that leukocytes exposed to activated complement components damage pulmonary vascular endothelial cells and stimulate synthesis of thromboxane A2 which causes pulmonary vasoconstriction.

6-Ketoprostaglandin F1 alpha↗

Creatine kinase response surfaces explored by use of factorial experiments and simplex maximization.

We conducted a five-component, five-level response-surface experiment to optimize the pH and the concentrations of magnesium, creatine phosphate, adenosine diphosphate, and buffer in an assay for creatine kinase. Under optimal conditions, creatine kinase activity was about 5% greater than that obtained with a previously reported assay (Clin Chem 23: 1569, 1977). We also applied a simplex maximization algorithm to the response-surface equation to locate areas of maximum sensitivity. Reaction conditions for two such areas were found, each yielding approximately 11% more activity than with the previously reported method.

Adenosine Diphosphate↗

Comparison of platelet thromboxane synthesis in diabetic patients on conventional insulin therapy and continuous insulin infusions.

Previous work has shown enhanced aggregation and thromboxane synthesis by platelets from diabetic subjects. We have compared thromboxane synthesis by platelets from normal subjects with that of platelets from two groups of insulin-dependent diabetic patients: one group receiving conventional depot insulin therapy and the other continuous subcutaneous insulin infusions. Thromboxane synthesis was significantly higher with platelets from the conventionally-treated diabetic patients than that observed for control subjects. Patients on continuous insulin infusions were similar to control subjects. This group of patients also had better control of glycemia. The effect on thromboxane production might be related to normalization of plasma lipids which occurs with continuous infusion insulin therapy.

Arachidonic Acids↗