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Biomedical subjects

S Ali

Publications and source records attributed to S Ali.

At least 217 records · Page 12Linked to original sources

Assessment of amplicons in the DNA from boiled tissue by PCR and AP-PCR amplification.

Polymerase chain reaction (PCR) is a technique sensitive enough to amplify small DNA fragments a billion-fold. The generation of amplicons either by PCR with a set of oligo primers or by arbitrarily primed AP-PCR with a single oligonucleotide primer is based on the availability of intact template and priming sites. With these approaches, it is possible to generate specific and random amplicons to assess the extent of damage to DNA caused by any of the physical, chemical, or environmental factors. We report the amplification of sex chromosome and autosome specific loci in the buffalo (Bubalus bubalis) genome by symmetrical and AP-PCR performed on DNA samples isolated from the muscle tissues that were boiled (treated) for different lengths of time. No difference was noticed in the amplification profile of DNA cooked for various lengths of time. However, after HinfI treatment, AP-PCR amplification of these DNAs revealed more bands on agarose gel than unrestricted samples. The successful amplification of the DNA samples isolated from the boiled tissues is attributed to the intactness of the amplicons. This suggests that despite storage for more than a year and subsequent heat treatment to the muscle tissues, the DNA remains a good substrate for PCR and AP-PCR amplification. Relevance of this work in the context of DNA probe technology is discussed.

Animals↗

Simultaneous measurement of intracellular calcium and tension in vascular smooth muscle: validation of the everted ring preparation.

This study details and validates a method that facilitates the eversion of vascular smooth muscle, a preparation employed in in vitro Ca2+ fluorometric assays. Vascular segments of porcine coronary artery, approximately 2 cm in length, were sutured to portions of polyethylene tubing inserted into the lumen of the vessel. After being secured and stabilized by the tubing, the vessel was easily everted while immersed in physiological buffer. Intracellular calcium concentrations ([Ca2+]i) and tension were measured simultaneously in everted rings denuded of the endothelium. In these preparations, increases in tension generated by KCl and prostaglandin F2 alpha (PGF2 alpha) were accompanied by increases in [Ca2+]i, as measured by fura-2 fluorescence. Isoproterenol (ISO) and sodium nitroprusside (SNP) elicited reductions in muscle tension as well as [Ca2+]i in both KCl- and PGF2 alpha-contracted rings. Comparison of the responsiveness of everted and uneverted coronary artery rings demonstrated that, while fura-2 fluorescence in uneverted rings was negligible, the magnitudes of contraction of both preparations to KCl or PGF2 alpha were similar. The relaxant responses to ISO and SNP were also similar in the everted and uneverted rings contracted with KCl or PGF2 alpha. The data suggest that the procedure employed in everting vascular segments maintains the integrity of the smooth muscle, thus making it a suitable model for the simultaneous measurement of [Ca2+]i and tension.

Animals↗

Effect of antagonists on DNA binding properties of the human estrogen receptor in vitro and in vivo.

Functional analyses, performed with the estrogen receptor (ER) isolated from different sources or produced with various expression systems, led to contradictory results concerning the role of estrogen (E2) and antiestrogens in ER DNA binding. Here we report the DNA-binding properties of the human ER and show that the wild type ER (HEG0) binds in vitro to an estrogen response element (ERE) as a dimer, irrespective of the presence or absence of estrogen. We also show that the two antihormones, 4-hydroxytamoxifen (OHT, a partial ER agonist) and ICI 164,384 (a pure antagonist) do not impair HEG0 dimerization and DNA binding in vitro. Exposure of HEG0 to elevated temperature (37 C) in vitro results in a much faster reduction of its binding capacity to an ERE in the absence of ligand or in the presence of ICI 164,384 than in the presence of either E2 or OHT. The Gly to Val mutation at amino acid 400 present in the human ER that we initially cloned (HE0), is responsible for an even faster heat inactivation of unliganded receptor compared with HEG0 and largely accounts for the previously observed in vitro ligand-dependent DNA binding of ER. We also show that, as previously observed for OHT, ICI 164,384 does not prevent ER binding to an ERE in vivo, even though ICI 164,384 acts as a pure antagonist for transcriptional activation by ER. We discuss these results in the context of a ligand-dependent interaction between the C-terminal region E, which contains the ligand-binding domain, and the N-terminal A/B region, which contains the activation function AF-1.

Animals↗

Prolactin-induced proliferation of Nb2 cells involves tyrosine phosphorylation of the prolactin receptor and its associated tyrosine kinase JAK2.

The interaction of prolactin with its receptor in the Nb2 cell line has been shown to induce the phosphorylation of cell-associated proteins and mitogenesis. It has been reported previously that one of these proteins, phosphorylated upon prolactin stimulation, was a tyrosine kinase. We have identified this kinase as JAK2, and demonstrate its association with the prolactin receptor. In addition, we show that the prolactin receptor itself becomes tyrosine phosphorylated upon ligand stimulation in Nb2 cells. These actions are time-dependent and occur rapidly after prolactin stimulation, with first the kinase being activated within 5 min and then the receptor being phosphorylated maximally at 20 min. Moreover, phosphorylation of both JAK2 and the receptor as well as Nb2 cell proliferation are dependent on the concentration of lactogenic hormone, resulting in a bell-shaped response curve similar to that observed in the two site model of hGH action. This indicates that early events in signal transduction as well as later events like mitogenesis and proliferation involve prolactin receptor dimerization. Together these data indicate that the prolactin receptor in Nb2 cells is associated to JAK2 and that upon ligand stimulation, and receptor dimerization, the kinase and the receptor are tyrosine-phosphorylated, which represents the first event in the process of prolactin receptor signal transduction in Nb2 cells.

Blotting, Western↗

Cholesterol's interfacial interactions with galactosylceramides.

Recently, the influence of acyl structure on galactosylceramide's (GalCer) interfacial phase behavior was studied [Ali, S., Smaby, J. M., & Brown, R.E. (1993) Biochemistry 32, 11696-11703]. Here, we show that acyl structure is a key parameter controlling GalCer's ability to interact with cholesterol. Different chain-pure GalCer species containing saturated (24:0, 18:0, or 10:0), or unsaturated (24:1 delta 15, 22:1 delta 13, or 18:2 delta 9, 12) acyl chains were synthesized. After measurement of the force-area behavior of mixed cholesterol/GalCer films at 24 degrees C, the average molecular area and average compressibility were determined as a function of film composition. Cholesterol exerts only a slight condensing effect when the GalCer species are liquid-ordered [liquid-condensed], with maximum condensation occurring near 0.25 mole fraction. However, cholesterol exerts a marked condensing effect on liquid-disordered (liquid-expanded) GalCer species regardless of whether the acyl chain is saturated or unsaturated. Maximum condensation occurs at cholesterol mole fractions between 0.3 and 0.4. We also compared cholesterol's relative condensing effect on liquid-expanded GalCer versus sphingomyelin. Cholesterol's condensation of either bovine brain or egg sphingomyelin is 25-30% greater than that observed with different liquid-expanded GalCer species. Aside from average area behavior, we assessed cholesterol's interfacial interactions with the various sphingolipids by determining the average compressibility as a function of composition. The compressibility of condensed GalCer derivatives changes very little upon addition of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Monitoring of bovine health problems of small dairy herds in Islamabad Capital Territory: design, data and disease frequencies.

A pilot health monitoring system was started in 1990 to develop statistically valid data for use in estimating the disease frequencies in dairy cattle and buffaloes. This paper presents the design of the monitoring programme and frequencies of selected diseases. Eighty herds were selected with typical livestock management practices of the farmers in the area. Veterinary assistants visited the farms once a month for 12 months to collect livestock inventory, production, disease and preventive treatment data. The incidence density method was used as a measure of disease frequency. In adults, breeding problems, mastitis and gastro-intestinal problems were the highest reported conditions. Respiratory problems were the commonest in young stock. The calves of both species frequently had gastro-intestinal and respiratory disease conditions. Most of the calf crop of both species were lost within the first 3 months of life.

Age Factors↗

Effect of low power microwave on the mouse genome: a direct DNA analysis.

The potential mutagenic effect of low power microwave at the DNA sequence level in the mouse genome was evaluated by direct DNA analysis. Animals were exposed to microwave at a power density of 1 mW/cm2 for 2 h/day at a frequency of 2.45 GHz over a period of 120, 150 and 200 days. HinfI digested DNA samples from testis and brain of control and exposed animals were hybridized with a synthetic oligo probe (OAT 36) comprising nine repeats of 5'-GACA-3'. As compared to control animals, band patterns in exposed animals were found to be distinctly altered in the range of 7-8 kb which was also substantiated by densitometric analysis. Though the mechanism of this rearrangement is not yet clear, the results obtained at the present dose are of significance. This dose, which has been set as the safe limit for general public exposure by the Non-Ionizing Radiation Committee of the International Radiation Protection Association, may imply a need for (re)evaluation of the mutagenic potential of microwaves at the prescribed safe limit for the personnel and people who are being exposed.

Animals↗

The International Headache Society (IHS) headache classification as applied to a headache clinic population.

Four hundred patients attending a headache clinic were classified using the IHS criteria. The majority required more than two, often three or four, diagnoses. Even though migraine was the most common diagnosis, only 1/4 of those with a migraine diagnosis had it as the only diagnosis. Seventy-five percent of migraine patients had coexistent chronic tension-type headache (CTTH), drug-induced headache or both. Ninety-six percent of patients diagnosed as having migraine with aura also suffered from migraine without aura. More than 1/3 of patients (37.7%) attending the clinic suffered from chronic daily headache (CDH) (chronic cluster headache excluded), which is not included as a separate entity in the IHS classification. Pure CTTH formed only a small minority of CDH, whereas 86.6% of CDH had migraine as one of the diagnoses. Drug-induced headache was a prominent second or third diagnosis. The advantages and disadvantages of multiple verses single diagnosis in CDH and the need to recognize the natural history of headache disorders in the classification are discussed.

Ambulatory Care Facilities↗

Attenuation of methamphetamine-induced neurotoxicity in copper/zinc superoxide dismutase transgenic mice.

Administration of methamphetamine (METH) to rats and nonhuman primates causes loss of terminals in the nigrostriatal dopaminergic system. The mechanism by which METH causes its neurotoxicity is not known. To evaluate further the role of oxyradicals in METH-induced neurotoxicity, we have tested its effects in CuZn superoxide dismutase (SOD) transgenic (Tg) mice, which express the human CuZnSOD gene. In non-Tg mice, acute METH administration causes significant decreases in levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striata and cortices of non-Tg mice. In contrast, there were no significant decreases in cortical or striatal DA in the SOD-Tg mice. The effects of METH on DOPAC were also attenuated in both structures of these SOD-Tg mice. Chronic METH administration caused decreases in levels of striatal DA and DOPAC in the non-Tg mice, whereas the SOD-Tg mice were not affected. These results suggest that METH-induced dopaminergic toxicity in mice may be secondary to increased production of reactive oxygen species such as the superoxide radical.

3,4-Dihydroxyphenylacetic Acid↗

Giant myofibroblastoma of the male breast.

Myofibroblastoma of the breast is a rare, benign neoplasm, seen predominantly in men. The gross appearance is that of a well-circumscribed nodule, characteristically small, seldom exceeding 3 cm. We report a case of giant myofibroblastoma measuring 10 cm and weighing 169 g in the breast of an 83-year-old man. Light microscopic, immunohistochemistry, and electron microscopic features are described. Histologically, these neoplasms may exhibit a varied cellularity that can be misinterpreted as sarcoma. However, they lack marked cellular pleomorphism, tumor necrosis, and mitosis and are characteristically composed of plump and long bipolar, spindly cells arranged in swirling fascicles with intervening broad collagen bands. As we report, immunostaining is strongly positive for vimentin, desmin, and muscle common antigen and negative for cytokeratins and S-100-associated protein. Electron microscopy shows predominantly cells suggestive of myofibroblastic differentiation. The patient has remained free of disease 2 years after mastectomy.

Aged↗

Patterns of tyrosine phosphorylation differ in vascular hypertrophy and hyperplasia.

Vascular smooth muscle cells (VSMC) undergo hypertrophy when exposed to thromboxane A2 and hyperplasia when exposed to phorbol 12-myristate 13-acetate (PMA) or platelet-derived growth factor (PDGF). Each of these three agonists stimulate rapid tyrosine phosphorylation of numerous VSMC proteins. The current studies were undertaken to identify proteins that are specifically tyrosine phosphorylated in one or the other growth response. All three agonists increased the phosphotyrosine content of multiple proteins. In Western analysis of phosphotyrosine immunoprecipitates, the hyperplastic agents PDGF and PMA increased tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1), GTPase-activating protein (GAP), and phosphatidylinositol-3-kinase (PI-3-kinase), while the hypertrophic agonist thromboxane failed to tyrosine-phosphorylate either of these three substrates. Tyrosine kinase inhibition with herbimycin A (5 microM) prevented agonist-stimulated tyrosine phosphorylation of PLC-gamma 1, GAP, and PI-3-kinase. In growth studies, herbimycin A inhibited PMA- and PDGF-induced hyperplasia but not thromboxane-stimulated hypertrophy. These results indicate that tyrosine phosphorylation of PLC-gamma 1, GAP, and PI-3-kinase are specific responses for VSMC hyperplasia but not thromboxane-stimulated hypertrophy.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗