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Biomedical subjects

M Ali

Publications and source records attributed to M Ali.

At least 451 records · Page 25Linked to original sources

Effects of sulfinpyrazone on platelet prostaglandin synthesis and platelet release of serotonin.

Sulfinpyrazone added to PRP inhibited the release of serotonin induced by collagen. The inhibitory effect depended strongly on the strength of the collagen stimulus. Serotonin release was also inhibited (up to 73%) in PRP prepared from subjects who had ingested the drug. This is the first demonstration of a direct effect of a sulfinpyrazone in vivo on in vitro tests of platelet function. Prostaglandin synthesis was studied with lysates of washed platelets, arachidonic acid-14C, and silicic acid chromatography to isolate a reaction product which was tentatively identified as thromboxane B2. Platelet prostaglandin synthesis was shown to be strongly inhibited by sulfinpyrazone. Inhibition was competitive with respect to substrate. It is proposed that effects of sulfinpyrazone on platelet function may be due to inhibition of prostaglandin synthesis. The competitive nature of sulfinpyrazone inhibition may explain why sulfinpyrazone is a strong inhibitor of the release reaction under conditions of dilute collagent stimulation but is weak in the presence of stronger stimuli. In comparing the potency of inhibitors of platelet prostaglandin synthesis the nature of inhibition must be considered. Competitive inhibitors may be incorrectly regarded as weak if studied only at high substrate concentration.

Blood Platelets↗

[Contribution to the problem of Arthrogryposis multiplex (author's transl)].

A case of Arthrogryposis multiplex appearing after birth and of no characteristical course is described. It is shown that in respect to existing works for diagnosis of Arthrogryposis multiplex the insufficiency of the hitherto existing valid diagnostic criterions is obvious. This especially because the pathogenesis of Arthrogryposis multiplex is unknown. Trying to look for the condition of the connective tissue of our patient, it was found that the collagen of skin shows a young matter of polymerisation and a nearly correlating electron microscopical picture.

Adult↗

A study of phosphoglycerate kinase in human erythrocytes. I. Enzyme isolation, purification and assay.

The enzyme ATP-3-phospho-D-glycerate-1-phosphotransferase (EC 2.7.2.3) (phosphoglycerate kinase) has been isolated from human red cells in crystalline form by a modification of the method of Yoshida and Watanabe (1972) J. Biol. Chem. 247, 440-445). The crystalline enzyme was further purified by electrofocusing using carrier ampholytes (pH 7-9). The isoelectric point of phosphoglycerate kinase was estimated to be 8.75. The specific activity of purified phosphoglycerate kinase from electrofocusing was 2200 units per mg of protein at pH 8.3 (37 degrees C). Enzyme activity was assayed in the forward direction leading from 1,3-diphosphoglycerate to a 3-phosphoglycerate using a fluorimetric procedure for NAD-coupled enzymes for the measurement of the reaction rate at very low substrate concentrations. The auxiliary indicator enzymes were added in excess to yield true initial velocity kinetics, i.e. with no time lag upon addition of substrate (1,3-diphosphoglycerate). This was established theoretically using a mathematical model and confirmed experimentally. Further phosphoglycerate kinase was shown to be the rate-limiting step when the assay conditions were varied.

Adenosine Diphosphate↗

A study of phosphoglycerate kinase in human erythrocytes. II. Kinetic properties.

Kinetic studies on phosphoglycerate kinase (EC 2.7.2.3) were performed in the forward reaction leading from 1,3-diphosphoglycerate to 3-phosphoglycerate. Substrate activation was observed at fixed levels of ADP or Mg2+ and varying concentrations of 1,3-diphosphoglycerate. A biphasic curve was obtained in both linear and double reciprocal plots demonstrating two Km values (Km1 1.9 - 10(-6) and Km2 9.8 - 10(6) M). Michaelis-Menten-type kinetics were observed in both the linear and double reciprocal plots at fixed levels of 1,3-diphosphoglycerate of ADP and varying concentrations of Mg2+. Apparent Michaelis-Menten kinetics were observed in linear plots when conditions of fixed concentrations of 1,3-diphosphoglycerate or Mg2+ were maintained with varying concentrations of ADP. However, the double-reciprocal plots demonstrated biphasic curves with two Km values (Km1 1.7 - 10(-5) and Km2 1.0 - 10(-4)M). Apparent negative cooperativity was observed with respect to 1,3-diphosphoglycerate and ADP. Phosphoglycerate kinase activity was found to be inhibited by AMP and 2,3-diphosphoglycerate. Substrate activation by 1,3-diphosphoglycerate was maintained in the presence of AMP or 2,3-diphosphoglycerate but at a reduced level of enzyme activity. AMP was found to inhibit enzyme activity non-competitively with respect to 1,3-diphosphoglycerate, ADP and Mg2+. 2,3-Diphosphoglycerate inhibits phosphoglycerate kinase activity with respect to 1,3-diphosphoglycerate, ADP and Mg2+. 2,3-Diphosphoglycerate inhibits phosphoglycerate kinase activity non-competitively with respect of 1,3-diphosphoglycerate.

Adenosine Diphosphate↗

Restricted addition of proviral DNA in target tissues of chickens infected with avian myeloblastosis virus.

Proviral DNA is synthesized within an hour after infection of chicken cells with an avian oncornavirus and is integrated into nuclear cellular DNA within a short time. The viral DNA appears to be synthesized as double-stranded molecules of approximately 6 X 10(6) daltons some of which are converted into supercoiled cricles perhaps as a requisite for integration. The endogenous v-DNA in normal chicken cells and both the endogenous and amv v-DNA in leukemic chicken myeloblasts are covalently linked with chromosomal DNA. There is no detectable free DNA either circular or linear present in leukemic cells several weeks after infection. The endogenous v-DNA which is transmitted vertically from parents to offspring is uniformly and stably distributed in all chicken organs. There are about 1-2 copies of endogenous provirus per haploid genome of all normal cells. This DNA is very closely related to RAV-O RNA. After infection with AMV it seems that target cells such as leukemic myeloblasts, RBC and nephroblasts acquire complete copies of AMV DNA. Interestingly, only these target cells can be converted to neoplastic cells in the chicken as well as in vitro. The target cells acquire 1-2 copies of AMV specific DNA per haploid genome in addition to the endogenous v-DNA. All the available evidence shows that leukemic and kidney tumor cells have acquired AMV v-DNA. It remains to be elucidated whether the newly added viral DNA is alone responsible for neoplastic changes or does so in conjunction with endogenous viral information.

Animals↗

Low fiber content of Connecticut diets.

Recent theories have postulated that low fiber diets are related to colon cancer and diverticulosis, and to atherosclerosis. These theories are based on British and African diet history information. There has been no recent assessment of fiber intake in an area of high incidence of colonic disease in the United States. Using recall diet histories in subjects with no disease and with colon disease, and correcting our data to account for any loss in recall history, we find a low daily fiber intake in all 21 subjects evaluated, mean 3.5 g, range 1.6 to 11 g. There was no statistical difference in intake among patients with or without colon disease. The data agree with the British findings. Since the incidence of the diseases in question is not uniform in the United States it is suggested that diet surveys are needed in areas where colon carcinoma is of low incidence.

Adult↗

The patterns of fetal haemoglobin production in leukaemia.

Elevated levels of haemoglobin F (Hb F) have been foudn in a wide range of haematological malignancies, but very high levels were found only in juvenile chronic myeloid leukaemia (JCML), and erythroleukaemia occurring in infancy. In both these disorders a reversion to a fetal form of erythropoiesis may occur, as judged by both the structure of the Hb F and by the disappearance of Hb A2 and the carbnoic-anhydrase isozymes during the course of the illness. The clinical picture of JCML is not always associated with a reversion to fetal erythropoiesis; there appears to be a heterogeneity of conditions with this clinical label. Thus the reversion to a completely fetal pattern of erythropoiesis seems to occur in a variety of leukaemias which start in early life. This change is associated with a uniformly bad prognosis. Of a group of 17 patients with acute myeloid leukaemia 15 developed an increase in the level of Hb F about 60 days after the commencement of treatment; significantly greater increases were observed in those achieving a clinical remission. The level of Hb F usually declined during remission but high levels persisted in a few cases. Increased levels of Hb F were found also in patients with other haematological malignancies who had undergone periods of marrow aplasia during treatment. In all cases the Hb F was heterogeneously distributed throughout the red cells. Analysis of gamma15 or gammaCB3 peptides of Hb F from a variety of leukaemias gave glycine compositions ranging from 0.20 to 0.85 residues with many values in the fetal range; all cases with a reversion to fetal erythropoiesis had values in the fetal range. Attempts to confirm the 'fetal' origin of the cells containing Hb F by means of other markers was possible only in the cases of JCML and in one child with erythroleukaemia. These studies indicate that in some forms of leukaemia there may be a genuine reversion to fetal erythropoiesis while in others the emergence of cells containing Hb F appears to be part of a rapid regeneration process occurring after a period of marrow aplasia. The diagnostic and prognostic value of these observations is discussed.

Adult↗

R-bodies of human rectal epithelial cells.

Distinctive globular bodies, ranging in diameter from 0.2mu to 1.5mu, were encountered in the cytoplasm of epithelial cells of human rectal mucosa. These profiles, surrounded by a unit membrane, contained a uniform population of electron-dense rods 50 nm wide and 100 to 250 nm long. Although neither the origin nor the relationships of these rod-containing bodies (R-bodies) to other cytoplasmic organelles could be established, morphologic and cytochemical studies demonstrated clear differences from multivesicular bodies.

Epithelial Cells↗

Avulsion of the gall bladder in blunt abdominal trauma.

Traumatic avulsion of the gall bladder, and its subsequent dislodgement into the pelvis has not previously been reported. The case described records severe damage to the biliary system without much damage to other viscera.

Abdominal Injuries↗

Quantitative and qualitative differences in DNA complementary to avian myeloblastosis virus between normal and leukemic chicken cells.

Hybridization of avian myeloblastosis virus (AMV) RNA with DNA immobilized on filters or in liquid with a vast DNA excess was used to measure the viral specific DNA sequences in chicken cells. Newly synthesized viral DNA (v-DNA) appears within an hour after infection of chicken embryo fibroblasts (CEF) with avian oncornaviruses. A fraction of newly synthesized v-DNA becomes integrated into the cellular genome and the remainder gradually disappears. A covalent linkage between v-DNA and cellular DNA was demonstrated to exist in CEF and in leukemic myeloblasts by alkaline sucrose velocity sedimentation. Hybridization of AMV RNA in DNA excess has revealed that there are 2 clases of viral specific sequences within normal as well as in leukemic cells. The 2 types of sequences differ in their rate of hybridization. The amount of both types of DNA sequences is about 2 times higher in leukemic cells than in normal cells. Both the fast- and slowly reacting sequences in leukemic cells exhibit a higher Tm (2 degrees C) than the respective DNA sequences in normal cells. Furthermore, when nucleotide sequences in AMV RNA complementary to normal DNA are removed first by exhaustive hybridization with normal DNA, the residual RNA only hybridizes with leukemic DNA but not with normal DNA. These results suggest that leukemic cells contain viral specific DNA sequences which are absent in normal cells. Endogenous v-DNA has been shown to be integrated in cellular DNA region(s) with a reiteration frequency of approximately 1,200 copies per cell and each integration unit appears to have a size approximately equivalent to the 35S RNA subunit of the viral genome. Viral sequences acquired after infection appear to be integrated in the unique region of cell DNA, or in tandem with the endogenous viral sequences.

Animals↗

The hydrolysis of some N-acylaspartic and N-acylglutamic monoamides in dilute mineral acid.

The release of ammonia by hydrolysis of N-benzoyl-L-asparagine, glycyl-DL-asparagine, L-asparagine, and succinamic acid, and of aniline from N-benzoyl-L-glutamic-alpha-anilide, N-benzoyl-L-aspartic-alpha-anilide, L-aspartic-alpha-anilide, and the monoanilides of succinic and glutaric acids is first-order with respect to substrate in dilute (0.4-0.03 M) aqueous hydrochloric acid at 100 degrees C. The first-order rate constants (kobs) for these reactions can be expressed as kobs = kintra + k2[H+]. The above hydrolyses are used as models for developing a tentative mechanism to account for the selective release of aspartic acid from proteins under these condiditons. The data are also used to suggest reasons why glutamic acid is not released with equal facility.

Amides↗

Synthesis of avian oncornavirus DNA in infected chicken cells.

The intracellular synthesis and integration of viral DNA (vDNA) into the host cell genome was studied in cultured chicken embryo fibroblasts infected with avian sarcoma or leukemia viruses. The newly synthesized vDNA was detected by hybridization with 70S viral RNA. Extraction of infected cell DNA by the selective procedure of Hirt resulted in the enrichment of newly synthesized vDNA in the low molecular weight supernatant fraction while leaving the bulk of cellular DNA containing integrated vDNA in the high molecular weight pellet fraction. This approach led to detection of intracellular vDNA synthesis within 1 h after infection and to vDNA integration into cellular DNA within 24 h. There was a several-fold increase in the vDNA content of infected cells during the initial phase of virus infection. But only a part of this newly synthesized vDNA appeared to become covalently linked with high molecular weight cellular DNA. Most of the remaining unintegrated vDNA gradually disappeared. The sedimentation profiles of minimally sheared cellular DNA in alkaline sucrose velocity gradients suggest that vDNA is synthesized as free linear molecules of approximately 3 x 10(6) daltons which subsequently are covalently linked to host cell DNA.

Alpharetrovirus↗