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Biomedical subjects

K Ahmed

Publications and source records attributed to K Ahmed.

At least 199 records · Page 11Linked to original sources
PubMed1979

Cardenolide analogues. 4. (20R)- and (20S)-Cardanolides: on the roles of the 20(22)-ene and 14beta-hydroxyl in genin activity.

(20R)-20,22-Dihydrodigitoxigenin (3a) and (20S)-20,22-dihydrodigitoxigenin (3b) were isolated from (20R,S)-20,22-dihydrodigitoxigenin (3) by three fractional crystallizations each from ethyl acetate. The two diastereomers have distinct NMR spectra and similar (Na+,K+)ATPase inhibitory activities (I50 = 1.1-1.4 X 10(-5) M)--about 1/100 as active as digitoxigenin (1). Their activity compared with other cardenolide analogues suggests a passive geometric role for the 20(22) double bond in eliciting (Na+,K+)ATPase inhibition, keeping the lactone carbonyl in the proper orientation. (20S)-3 beta,14 beta-Dihydroxy-22-methylene-5 beta,14 beta-cardanolide (7a) was then synthesized from 3a, and (20R)-3 beta,14 beta-dihydroxy-22-methylene-5 beta,14 beta-cardanolide (7b) from 3b. They were found to be equivalently active in inhibiting (Na+,K+)ATPase, with I50 values of 7.0 x 10(-5) M. Although it has been usually believed that the 14 beta-hydroxyl of cardenolides increases binding to the receptor, 2b (the 14-ene derivative of 7b) was more than twice as active (I50 = 3.0 X 10(-5)) than either 7a or 7b.

Animals↗
PubMed1978

Effects of polyamines on prostatic chromatin- and non-histone-protein-associated protein kinase reactions.

Studies are presented on the influence of polyamines on prostatic chromatin- and non-histone-protein-associated protein kinase reactions involving both exogenous and endogenous substrates. The activities toward the model acidic protein substrate, dephosphophosvitin, were maximal at 160--200mM-NaCl (or -KCl or -NH4Cl). Under these conditions, spermidine and spermine added in concentrations up to 2mM were essentially without effect. However, without addition of NaCl to the medium, marked stimulation of these reactions was elicited by these polyamines at 1--2mM concentrations. The stimulatory effects were not due to non-specific changes in the ionic strength or to substitution of spermine for Mg2+, as maximal stimulation by 1 mM-spermine was observed only at optimal (2--4mM) Mg2+ concentrations. Qualitatively similar effects of polyamines were observed with enzyme preparations from the prostates of castrated rats, and with chromatin and non-histone-protein preparations from other tissues besides ventral prostate. When phosphorylation of endogenous non-histone proteins of the chromatin was measured, spermine stimulated both the initial rates and the final extent of transphosphorylation, even in the presence of optimal concentration of NaCl. By contrast, spermine or spermidine had no effect on the chromatin- and non-histone-protein-associated protein kinase reactions determined with lysine-rich histones as substrates. Chemically NN-dimethylated dephosphophosvitin was a less active substrate for the chromatin-associated protein kinase, but its phosphorylation was more markedly stimulated by spermine in comparison with unmodified dephosphophosvitin. These observations hint that the polyamine stimulations of the various protein kinase reactions may be due to effects on the conformations of the non-histone protein substrates rather than on the kinases themselves.

Animals↗
PubMed1978

Effects of polyamines on partial reactions of membrane (Na+ + K+)-ATPase.

Spermine and spermidine inhibit the (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) reaction so that the effect increases as the ionic content due to Na+ and K+ in the reaction is reduced. Several other amines inhibit (Na+ + K+)-ATPase to varying degress and methylglyoxal-bis-(guanylhydrazone) was the most potent inhibitor among those tested. The inhibition by polyamines of the ATPase is uncompetitive with respect to Mg2+ and ATP activation of the reaction. Various naturally occurring polyamines and other amines inhibited Na+ activation of (Na+ + K+)-ATPase as well as Na+-dependent phosphoenzyme formation in an apparently competitive manner with respect to Na+. Likewise, K+-activation of (Na+ + K+)-ATPase as well as K+-p-nitrophenyl phosphatase was inhibited in an apparently competitive manner with respect to K+. Both the cation charge and structure (e.g., aliphatic chain length) may contribute to the inhibitory effects of the amines; however, Na+ sites appear to be more sensitive to cation charge than the aliphatic chain length of the amine, whereas the opposite appears to be true for K+ sites. The results do not indicate a specific effect of polyamines on (Na+ + K+)-ATPase or its partial reactions.

4-Nitrophenylphosphatase↗
PubMed1978

Acidic-phosphoprotein phosphatase activity of rat ventral prostate nuclei: apparent lack of effect of androgens.

A protein phosphatase activity has been demonstrated in nuclei of rat ventral prostate utilizing 32P-labelled phosvitin as a model acidic phosphoprotein substrate. This phosphoprotein phosphatase has a pH optimum of 6.7, is unaffected by the sulphydryl protecting agent 2-mercaptoethanol, and requires a divalent cation for maximal activity. Of the various divalent cations tested, Mg2+ is the most effective in reactivating the EDTA-inhibited enzyme. The phosphatase is inhibited by sodium flouride, sodium oxalate, N-ethylmaleimide, ATP and ADP but is relatively insensitive to ammonium molybdate. Increased ionic strength of the reaction medium also causes a reduction in the enzyme activity, e.g., by 48% at 200 mM sodium chloride. The activity of the acidic phosphoprotein phosphatase did not change significantly at 48 h or 96 h post-orchiectomy when expressed per unit of nuclear protein. However, it is reduced by approx. 30% at these times after castration if based on DNA content. The decline in activity per nucleus reflects the decrease in the realtive nuclear protein content observed at 48 h or 96 h post-orchiectomy. This suggests that the decline in the phosphorylation of prostatic nuclear acidic proteins which occurs upon androgen withdrawal is not due to increased nuclear phosphatase activity.

Androgens↗
PubMed1978

Methylene blue as an inhibitor of stone formation.

Kinetics of growth and dissolution of calcium oxalate monohydrate were examined in the presence of small concentrations of methylene blue. The data presented show moderate retardation in growth and dissolution rates. It was also found that methylene blue decreased the decalcification rate of calcium oxalate renal calculi. The implications of these findings in the treatment of urolithiasis are discussed.

Calcium↗
PubMed1978

Coxsackievirus in an infant chimpanzee.

Coxsackie B viruses may cause a severe, often fatal, illness in newborn and infant human subjects. As recorded in this case, infant chimpanzees respond similarly to Coxsackie B-5 virus.

Animals↗
PubMed1977

Cardenolide analogues. 2. 22-Methylenecard-14-enolides.

22-Methylene-3beta-hydroxy-5beta,20(S)-card-14-enolide (11) and 22-methylene-3beta-hydroxy-5beta,20(R)-card-14-enolide (12) were synthesized from digitoxin (1). Attempts to prepare the 14beta-hydroxy-22-methylene analogues were unsuccessful. The 20(R) isomer (12) was found in Na+, K+-ATPase inhibition studies to be twice as active as 14-dehydrogitoxigenin (17). The 20(S) isomer (11) was significantly less active than 17. The hydrolysis of steroid 3beta-tert-butyldimethysilyl ethers was also found to be much more difficult than with nonsteroids.

Adenosine Triphosphatases↗
PubMed1976

Presence and androgen control of an alkaline phosphatase in the nucleus of rat ventral prostate.

The presence of alkaline phosphatase (EC 3.1.3.1) activity has been demonstrated in nuclei of rat ventral prostate. This enzyme activity remained after washing of isolated nuclei with 0.5% Triton X-100; an acid phosphatase initially present with the nuclear fraction was removed by this treatment. The nuclear alkaline phosphatase, examined by utilizing p-nitrophenyl phosphate as substrate, had a pH optimum of 9.5-10.3, and a broad substrate specificity: p-nitrophenyl phosphate greater than phosphothreonine greater than beta-glycerophosphate greater than phosphoserine. The nuclear phosphatase was sensitive to denaturation by heat or urea treatments and was also inhibited by Pi, L-phenylalanine, homoarginine, dithiothreitol, and EDTA. The EDTA-inhibited enzyme was maximally reactivated by Zn2+, although Mg2+, or Ca2+ were also effective at somewhat higher concentrations. Orchiectomy of adult rats resulted in an increase in the nuclear alkaline phosphatase activity (2-3-fold at 24 or 48 h postorchiectomy). A decline in the protein: DNA ratio also occurred following orchiectomy, but the increase in phosphatase specific activity was evident whether expressed per unit of protein or per unit of DNA. Testosterone replacement following orchiectomy abolished the increase in nuclear phosphatase activity. The results suggest that the prostatic nuclear alkaline phosphatase may be involved in events related to inactivation of the prostate nucleus following androgen deprivation.

Alkaline Phosphatase↗
PubMed1976

Na+-dependent phosphorylation of the rat brain (Na+ + K+)-ATPase. Possible non-equivalent activation sites for Na+.

The steady state levels of Na+-dependent phosphoenzyme (E-P) in the (Na+ + K+)-ATPase (EC 3.6.1.3) of rat brain, obtained from a time course study of phosphoenzyme formation at 4 degrees C, were dependent on the concentration of Na+ in the reaction and were maximal in the presence of 64 mM Na+. The plot of phosphoenzyme vs. Na+ concentration gave a curve which on conversion to a double reciprocal plot (1/E-P vs. 1/Na+) gave a line with two breaks, yielding apparently three linear segments. This may be taken to indicate the presence of multiple Na+ sites for the formation of the phosphoenzyme. To test this hypothesis further, the following approach was taken. By making the assumption that the phosphoenzyme may represent bound Na+, it was possible to subject the data to rigorous multiple-site analysis by utilizing steady-state binding equations described by Klotz and Hunston (1971) (Biochemistry 10, 3065-3069), and by Scatchard (1949) (Ann. N.Y. Acad. Sci. 51, 660-672). The analysis of the data by these methods suggests that there may be three non-equivalent Na+ activation sites for the formation of Na+-dependent phosphoenzyme in the (Na+ + K+)-ATPase. The estimated intrinsic association constants (Ka) for activation by Na+ at each of the three sites were 3.4, 0.295, and 0.025 mM-1, respectively.

Adenosine Triphosphatases↗
PubMed1976

Cardenolide analogues. 1. A 17beta-unsaturated aldehyde.

A 17beta-unsaturated aldehyde analogue [3beta,14beta-dihydroxy-5beta-pregn-17beta-trans-20-en-22-al (7)] of the cardenolides was synthesized and studied. In earlier studies by Rappoport, unsaturated aldehydes were found to be highly active electrophiles, more active, for example, than unsaturated nitriles or methyl esters. The synthesis followed in part a scheme previously reported by Thomas for the syntheses of the 17beta-unsaturated nitrile 9 and the 17beta-unsaturated methyl and ethyl esters 8 and 10. Both 9 and 8 are more Na+,K+-ATPase inhibiting and slightly less inotropic than digitoxigenin (1b). However, the unsaturated aldehyde 7 was less Na+,K+-ATPase inhibiting (I50 - 9.9 +/- 0.7 X 10(-7) M) and less inotropic (100% increase in contractile force at 8.5 +/- 1.0 X 10(-6) M) than 1b (I50 - 4.6 +/- 1.6 X 10(-7) M; 100% increase at 3.0 +/- 1.0 X 10(-7) M).

Adenosine Triphosphatases↗
PubMed1976

The differential response of prostatic nucleolar and extra-nucleolar protein phosphokinase activities following androgen deprivation.

Protein phosphokinase activities of nucleolar and extra-nucleolar compartments of rat ventral prostate nuclei were measured using the model acidic phosphoprotein, dephosphophosvitin, as substrate. Following orchiectomy, the activity in both of these fractions declined; however, the kinase activity of the nucleolus decreased at a much greater rate than that in the extra-nucleolar portion of the nucleus. Testosterone maintenance of castrated animals prevented this decline in activity. The regulation of protein phosphokinases which phosphorylate prostatic nucleolar acidic proteins may be an important mechanism in the androgen mediated activation of the nucleolus in this target tissue.

Animals↗