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Biomedical subjects

M Ali

Publications and source records attributed to M Ali.

At least 325 records · Page 18Linked to original sources

A comparison of transketolase assay and transketolase and lactate dehydrogenase activity levels in whole blood and red cell hemolysates and in leukocytes.

1. A study was made of transketolase activity in red and white blood cells and of conditions for assay for transketolase activity and for assessment of the "TPP effect" in human and rat blood. 2. The ratio of the transketolase activity in white cells to that in red cells varied between 23 and 93. 3. Red cells or white cells can both be used for assessment of transketolase activity and the "TPP effect", but the best source for evaluation of transketolase activity and the percent change on addition of thiamin diphosphate appears to be whole blood.

Animals↗

Effects of thyroid deficiency on the vasopressin receptors in the kidney of developing and adult rats. A comparative study of hormonal binding and adenylate cyclase activation.

The effects of propylthiouracil (PTU) treatment on renal vasopressin sensitive adenylate cyclase in young and adult rats were studied by measuring the binding of tritiated vasopressin and adenylate cyclase activation by vasopressin in kidney medulla plasma membranes. Thyroxine therapy completely corrected the effects of PTU treatment on the vasopressin-adenylate cyclase system. Thus, the abnormalities observed after a such treatment are directly related to thyroid deficiency and not to toxic effects of PTU. The inability of the kidney to normally concentrate urine in developing and adult animals with induced hypothyroidism was mainly related to the reduction of the number of binding sites without significant changes in the basal and guanylyl-imidodiphosphate (Gpp(NH)p)-stimulated adenylate cyclase activities, the apparent dissociation constant (Kbind) of labeled vasopressin from its specific receptor and the apparent activation constant (Kact) of vasopressin for adenylate cyclase. These results also show that thyroid deficiency has more effect on the ontogenesis of receptors than on their turnover, and demonstrate that a normal antidiuretic response occurs at very low receptor occupancy. Since, on the one hand, the hypothyroidism-induced abnormalities in renal medulla responsiveness to vasopressin were reversible and, on the other, only a permanent therapy consisting of two daily physiological doses of thyroxine from birth to the age of sacrifice fully restored them, the responsiveness of developing kidney to thyroid hormones appears to be fundamentally different from that of the CNS.

Adenylyl Cyclases↗

A comparative study of plasma vasopressin levels and V1 and V2 vasopressin receptor properties in congenital hypothyroid rat under thyroxine or vasopressin therapy.

The effects of propylthiouracil (PTU) treatment on the plasma vasopressin level, on the number of hepatic (V1) or renal (V2) vasopressin receptors and on the hormone-sensitive adenylate cyclase activity in the kidney of developing rats were studied in parallel. In addition, we investigated the corrective effects of thyroxine therapy on the plasma vasopressin level and parameters related to the liver, and the effects of vasopressin therapy on the parameters related to the kidney. As already reported in the case of the number of V2 receptors and adenylate cyclase activity in the kidney, the deficient plasma vasopressin level in hypothyroid rats was completely corrected by two daily physiological doses of thyroxine given from birth to the age of sacrifice (1 month). Unlike the V1 receptors, the V2 receptors are known to be highly dependent on their specific circulating ligand. Since, first of all, the deficit was similar in the numbers of V1 and V2 receptors in hypothyroid rats, and, secondly, the treatment of hypothyroid rats by two daily physiological doses of long lasting vasopressin was found ineffective to recover the deficit in the number of V2 receptors, it can be concluded that thyroid deficiency directly alters vasopressin receptor biosynthesis in both liver and kidney, instead of acting via the depressed plasma vasopressin level.

Animals↗

Antibody responses to hemodialysis-related antigens in chronic hemodialysis patients.

Allergic-type reactions during hemodialysis are sometimes due to sensitization to ethylene oxide. To examine the possibility that additional antigens might be a basis for unexplained reactions, antibodies to formaldehyde and phthalate-related antigens and to dialyzer extracts were measured. Unselected sera from 113 chronic hemodialysis patients (CHP) and 200 control subjects were tested for IgG antibodies to formaldehyde-treated human serum albumin (HSA). The IgG antibody activity was confirmed in sera of five CHP who had used formaldehyde-treated dialyzers. These antibodies also reacted with formaldehyde-treated red blood cells. Sera from 71 CHP and 80 controls were tested for IgE antibodies to diethylphthalate-treated HSA; antibody was detected in two CHP sera. With extracts from hollow-fiber dialyzers, IgG antibody was detected in approximately 1/3 and IgM antibodies in approximately 1/2 of CHP sera. This antibody was found in comparable numbers of control sera. It was concluded that these additional substances are immunogenic and could be involved in allergic-type reactions.

Anaphylaxis↗

The effect of prostaglandin synthesis inhibition on motility of the sheep ureter.

To determine the effect of prostaglandin-synthesis inhibition on ureteral motility, isolated rings of sheep ureters were suspended for recording isometric tension in organ baths filled with Krebs-Henseleit solution. The non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin and diclofenac sodium (10(-5) M) inhibited rhythmic ureteral motility by reducing frequency, amplitude and finally stopping contractions. Prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha and thromboxane B2 were determined by radioimmunoassay in the bathing solution before and after addition of NSAIDs. Peak contractile activity at 100 min of suspension was associated with increased concentration of all three prostanoids and 50 min after addition of indomethacin and diclofenac sodium when rhythmic contractions stopped, concentration dropped to low levels. The concentration of prostaglandins released into the organ bath were not quantitatively related to the frequency of contractions and therefore do not seem to affect pacemaker activity within ureteral smooth muscle but rather intercellular recruitment of myo-genically active fibres. These findings indicate that prostaglandins play a role in the motor control of the ureter, and that non-steroidal anti-inflammatory drugs exert an inhibitory action.

6-Ketoprostaglandin F1 alpha↗

Evidence for the involvement of DNA topoisomerase II in neutrophil-granulocyte differentiation.

Agents that slow cellular proliferation usually stimulate myeloid differentiation. The demonstration in this report of an anomalous inhibitory behavior of the epipodophyllotoxin VP16-213, an agent known to inhibit the enzyme DNA topoisomerase II, prompted us to investigate the role of this enzyme in both changes in DNA supercoiling and in DNA strand breakage and reunion events occurring during the induction of neutrophil-granulocyte differentiation. We recently reported that retinoic acid, an inducer of granulocytic differentiation, stimulates transient relaxation of DNA supercoiling. We now show that this is associated with the formation of small numbers of protein-linked DNA breaks (a characteristic of topoisomerase reactions). Both events are perturbed by VP16-213, and since this agent inhibits subsequent differentiation, these observations raise the possibility of a role for DNA topoisomerase II in granulocytic differentiation. The possible relevance of these findings to mechanisms of leukemogenesis is discussed.

Cell Differentiation↗

[Histological, biochemical and immunocytochemical data on the postnatal development of the hypothalamic magnocellular nucleus in the congenital hypothyroid rat].

1 The effects of congenital hypothyroidism on the postnatally developing hypothalamus and, particularly on the developing magnocellular nuclei and their vasopressinergic neurons, were studied by means of complementary approaches, such as histology, biochemistry and immunocytochemistry. 2 In normal rat, all the results show a precocious development of hypothalamus, and particularly of its magnocellular nuclei. 3 In hypothyroid rat, in showing that the nucleic acid and protein content of hypothalamus is diminished by the same magnitude than its wet weight, the results display a normal average cellularity and cell size. In the magnocellular nuclei of 10, 20 and 30 day-old rats, the neuronal density and cell size appear to be unaffected, except for the NSO at 35 days of age in which the two parameters are increased and decreased, respectively. With respect to vasopressinergic neurons in 35 day-old rats, their density and percentage in total cell population, as well as the axonal density are somewhat increased, the greater differences always significant being shown only in the NPV. Whatever the nuclei considered, the density of axonal varicosities does not differ from normal value. Finally, the vasopressin concentration of hypothalamus is significantly increased. Thus, it may be concluded that the mainly prenatal development of these vasopressinergic hypothalamic nuclei seems to be relatively spared from neo- and postnatal thyroid deficiency.

Animals↗

Origin of corticosteroid-binding globulin in fetal rat. Comparative dynamics of corticosteroid-binding globulin, alpha-fetoprotein, and albumin secretion in primary cultures of fetal rat hepatocytes.

The origin of corticosteroid-binding globulin (CBG) and its evolution in comparison with alpha-fetoprotein (AFP) and albumin synthesis, during early development of rat liver (days 13 and 15 of fetal life), have been investigated using cultured fetal hepatocytes. Synthesis and secretion of CBG, AFP, and albumin is evidence by cycloheximide-sensitive [14C]leucine incorporation into immunoprecipitable polypeptides secreted by cultured hepatocytes into the medium, two-dimensional immunoelectrophoretic and autoradiographic identification of newly synthesized labeled proteins, corticosterone and estradiol-17 beta binding to CBG and AFP, respectively, and indirect immunofluorescence localization of AFP, albumin, and CBG in cultured fetal hepatocytes. CBG, albumin, and AFP accounted for 6, 11, and 25% (in 13-day-old rat fetuses) and 5, 15, and 28% (15-day-old rat fetuses), respectively, of the total secreted proteins in the culture medium. The rates of CBG, AFP, and albumin (counts/minute of secretion [14C]leucine incorporated per milligram of cell protein/hour of culture) in the hepatocytes of 15-day-old rat fetuses were 1.48-, 2.1-, and 2.57-fold higher, respectively, than in the 13-day-old rat fetuses. These results indicate that fetal liver is also active in CBG synthesis, along with AFP and albumin, as early as day 13 of fetal life and that the synthetic rates of these secretory proteins depend upon the developmental stage of the fetal liver. This developmental related change in the rate of synthesis of CBG by the fetal hepatocytes may regulate the level of free (active) glucocorticoid in the fetal circulation and thereby the initiation and regulation of glucocorticoid-dependent processes during the crucial stages of the differentiation of fetal liver and other developing tissues.

Albumins↗

Vasoconstrictor components in the Arabian Gulf catfish (Arius thalassinus, Ruppell) proteinaceous skin secretion.

The Arabian Gulf catfish (Arius thalassinus, Ruppell) produces toxic substances from its skin and from venom glands located near the base of the pectoral fins. Investigation of the pharmacological properties of the skin toxin have previously shown cholinergic vasoconstrictor activity in umbilical arteries. Cholinergic vasoconstriction was confirmed in sheep renal arteries. This activity was partially blocked by atropine, while most of the residual contraction was eliminated by simultaneous addition of indomethacin. Skin toxin treatment of arterial specimens caused a release of prostaglandin (PGE2, TXB2 and 6-keto-PGF1 alpha) into the organ bath. Prostaglandin release was blocked by pretreatment with indomethacin. Heat denaturation of skin toxin caused a loss of only the indomethacin-sensitive muscle contraction activity; most of the residual activity was blocked by atropine.

Animals↗

Selective suppression of platelet thromboxane formation with sparing of vascular prostacyclin synthesis by aqueous extract of garlic in rabbits.

It has been suggested that a drug which selectively inhibits platelet thromboxane synthesis, sparing vascular synthesis of prostacyclin, would be more effective as an anti-thrombotic agent. We studied the effect of an aqueous extract of garlic on the production of thromboxane and prostacyclin by rabbit whole blood and aorta in vitro and ex vivo. A dose-dependent inhibition of thromboxane production was observed during blood clotting. Synthesis of prostacyclin was not affected by any concentration of garlic extract used in the experiment. A slight but insignificant reduction in the vascular synthesis of prostacyclin was observed at the highest concentration of garlic used in in vitro experiments. The synthesis of thromboxane by aorta was completely suppressed at all the concentrations of garlic tested. A similar pattern of results was observed after intraperitoneal administration of garlic (1 ml/kg) for one week on the enzymatic synthesis of thromboxane and prostacyclin of these tissues ex-vivo. Aortic synthesis of prostacyclin was significantly increased in the garlic treated rabbits compared to the controls. The data obtained from these rabbit experiments suggested that it may be possible to achieve a selective suppression of thromboxane formation by platelets with sparing of vascular synthesis of prostacyclin by garlic treatment.

6-Ketoprostaglandin F1 alpha↗

Lipid composition of the epidermal gel secretion from the Arabian Gulf catfish (Arius thalassinus Ruppell).

Lipids associated with a threat induced epidermal gel secretion from the catfish, Arius thalassinus, have been analyzed. Phospholipids, neutral lipids and glycolipids are all present and each of these subclasses has been analyzed by thin layer and gas chromatography with a general similarity with membrane lipids being noted. The epidermal gel lipids differed from total liver lipids of the catfish. Fatty acid analysis showed the gel lipid to be rich in the unsaturated fatty acids: oleate (omega 7, C18:1), arachidonate (omega 6, C20:4), and docosahexaenoate (omega 3, C22:6). Some prostaglandins were quantitated in lipid extracts from the epidermal gel.

Animals↗

Modulation of mouse skin tumor promotion by dietary 13-cis-retinoic acid and alpha-difluoromethylornithine.

The effects of dietary supplementation of 13-cis-retinoic acid (13-cis-RA) and alpha-difluoromethylornithine (DFMO) in the drinking water on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation was determined. Administration of 13-cis-RA in the diet and DFMO in the drinking water was started 1 week and 2 days before the first TPA application to the dimethylbenz[a]anthracene-initiated skin of either female CD-1 or SENCAR mice, respectively. Dietary 13-cis-RA failed to inhibit both the tumor yield and the incidence; papillomas per mouse at 0, 5, 50, 100 and 200 mg/kg diet 13-cis-RA doses were 25, 30, 22, 28 and 25 respectively at 18 weeks of promotion treatment and at all doses 100% of the mice bore papillomas. However, dietary 13-cis-RA dramatically reduced the size of skin tumor promoted with TPA. 13-Cis-RA at doses of 5, 50, 100 and 200 mg/kg diet inhibited skin papillomas (greater than 4 mm diameter) per mouse by 28, 55, 76 and 93%, respectively. Retinoid treatment did not affect body weight gains and the survival was more than 80% in all groups. In accord with our previous findings, DFMO when given in drinking water, was a very effective inhibitor of mouse skin tumor promotion by TPA; DFMO at 0.25% concentration inhibited the number of papillomas by 50%. Inhibition of skin tumor promotion by combined treatments with dietary 13-cis-RA (100 mg/kg) and DFMO (0.25%) in the drinking water was possibly additive. The retinoid and DFMO preclude TPA-increased ornithine decarboxylase (ODC) activity and the accumulation of putrescine by differential effects on ODC, an enzyme associated with skin tumor promotion by TPA.

Animals↗

Iron state in alpha and beta thalassaemia trait.

The iron state was examined in two groups of pregnant women who were carriers of alpha and beta thalassaemia genes. In both groups the haematological expression of the disease--namely, haemoglobin and mean cell haemoglobin concentrations--was nearly identical. In patients with alpha thalassaemia the ferritin concentrations and percentage of ferritin deficiency was the same as in normal pregnant patients, whereas in those with beta thalassaemia the ferritin concentrations were usually much higher and iron deficiency four times less common. This variance appears to be explained by different degrees of extravascular or intravascular haemolysis between the two thalassaemias as assessed by the activities of serum alpha hydroxybutyrate dehydrogenase.

Adult↗

Ontogenesis of the kidney in the congenital hypothyroid rat. Biochemical and anatomical parameters of general development.

The effect of congenital thyroid deficiency upon the postnatal development of the rat kidney has been studied by measuring the nucleic acid, protein and lipid contents, and the area and thickness of the different regions in the organ, i.e. cortex, outer and inner medulla. Thyroid deficiency, induced by daily propylthiouracil treatment, strongly affects the development of the renal cortex. The medulla, and still more its inner part which develops early and partly before the onset of thyroid function, is relatively preserved. These effects are completely corrected by daily thyroxine therapy, excluding a possible toxic effect of the antithyroid drug. Moreover, they are partly reversible after cessation of propylthiouracil treatment.

Aging↗

Doxorubicin-induced congestive heart failure in adults.

The prognosis of doxorubicin-induced congestive heart failure (CHF) is reported to be poor. To define the clinical course of doxorubicin-induced CHF, the authors reviewed their experience with 43 patients with this diagnosis. The median age of the total group was 55 years (range, 23-69); the median cumulative dose of doxorubicin was 450 mg/m2 (range, 200 mg/m2-1150 mg/m2). A majority of the patients had a diagnosis of breast cancer. The median survival of the whole group estimated by means of a Kaplan-Meier plot was 112 weeks. Twelve of 43 patients (28%) died of CHF, 7 of them (16%) because of fulminant failure in less than 8 weeks and the remaining 5 because of a more protracted course with recurrent episodes of cardiac decompensation. Twenty-five of the 43 patients (58%) achieved complete control of CHF. In the remaining 6 patients (14%), CHF had improved but was not completely controlled at the time of death, which was secondary to progressive tumor. Treatment consisted of standard therapy with digitalis and diuretics. Survival was significantly shorter in patients who presented with class IV dyspnea and in those who developed CHF less than 4 weeks after administration of the last dose of doxorubicin. The authors conclude that in a majority of patients, doxorubicin-induced CHF is easily treatable and frequently controlled with digitalis and diuretics.

Adult↗