Biomedical subjects

H Ali

Publications and source records attributed to H Ali.

At least 19 recordsLinked to original sources

PubMed2026

Genomic characterisation and lytic potential of phage SF01 against multidrug-resistant Salmonella enterica subsp. enterica, a key agent of infection in poultry.

1. Salmonella enterica remains the key cause of salmonellosis in poultry, causing high morbidity and mortality. Due to the unprecedented resistance of S. enterica to antibiotics, bacteriophages have emerged as a powerful alternative to conventional antibiotics treatment for salmonellosis.2. In this study, a strain was isolated from infected broiler chickens and whole-genome sequencing (WGS) identified the strain SFD-01 as S. enterica subsp. enterica. Bioinformatics analyses revealed that the genome was 4.6 Mb in size with 4559 coding sequences (CDS), 77 tRNAs and 4 rRNAs. Additionally, 119 virulence genes, 125 antimicrobial resistance genes, 5 mobile genetic elements, 2 prophages and multiple copies of pathogenicity islands (SPI) were identified in the genome.3. To address this, bacteriophage SF01 was isolated from wastewater near a chicken slaughterhouse against host strain SFD-01. Transmission electron microscopy revealed that the phage had an 85-nm icosahedral head and a 130-nm long contractile tail. The Felixounavirus SF01 exhibited high stability across pH 3-9. Phage lytic activity at a multiplicity of infection of 0.01 restricted the bacterial growth.4. Whole genome analysis (WGS) identified phage SF01 as a Felixounavirus with 88-kb genome composed of 174 CDS, 20 tRNA genes and with no lysogenic markers, resistance genes or virulence factors. The strict lytic potential of phage SF01 makes it a highly viable option for use in the potential biocontrol of the novel strain S. enterica subsp. enterica serotype 42:z4,z23.

Felixounavirus↗

PubMed1992

Synthesis, receptor binding and target-tissue uptake of carbon-11-labeled carbamate derivatives of estradiol and hexestrol.

Carbon-11-labeled estradiol and hexestrol derivatives were prepared via the reaction of [11C]ethylchloroformate with the 2- and 4-amino derivatives of estradiol, the 3'-amino derivatives of hexestrol, and the 1-aminophenoxy derivatives of hexestrol and 1-norhexestrol. The corresponding nonradioactive carbamates were prepared for chemical characterization and in vitro receptor binding assays. The positions of the substituents on the parent molecules were selected with a view to minimize interference with the receptor binding process. In spite of this, affinity for the estrogen receptor was strongly impaired for all carbamate derivatives. Likewise, in vivo, the [11C]carbamate analogs failed to localize in receptor rich tissue via an estrogen receptor mediated process.

Amines↗

PubMed1992

Concurrent post-streptococcal carditis and glomerulonephritis: serial echocardiographic diagnosis and follow-up.

The two non-suppurative post-streptococcal events, acute rheumatic fever and acute glomerulonephritis, rarely occur simultaneously. We describe such a patient, a 16-year-old male who was admitted with fever, agitation and confusion. Blood work-up showed high antistreptolysin O titre, raised serum creatinine and low complement levels. Urinalysis showed RBC casts. Echocardiographic examination demonstrated markedly impaired left ventricular systolic and diastolic function and three large thrombi in the apex. Serial echocardiographic examinations revealed improvement of cardiac function and the resolution of the thrombi and both cardiac and renal function returned to normal after 3 weeks of treatment.

Acute Disease↗

PubMed1992

Photosensitizing activity of water- and lipid-soluble phthalocyanines on prokaryotic and eukaryotic microbial cells.

The photosensitizing activity of lipophilic zinc-phthalocyanine (Zn-Pc) and its water-soluble sulphonated derivative (Zn-PcS) towards Streptococcus faecium and Candida albicans was studied and correlated with the amount of cell-bound photosensitizer. With both micro-organisms Zn-PcS was more tightly bound in larger amounts than Zn-Pc in the protoplasts of the cytoplasmic membrane. As a consequence, the photoinduced damage in S. faecium initially involved membrane proteins, while DNA was modified only upon prolonged irradiation. For C. albicans only Zn-PcS showed a preferential affinity for the spheroplasts and the decrease in cell survival was not accompanied by detectable modifications of the electrophoretic pattern of membrane proteins. The photoinduced ultrastructural alteration of both micro-organisms suggests damage at membrane level. This would indicate the involvement of different targets in bacteria and yeast for phthalocyanine photosensitization.

Candida albicans↗

PubMed1992

[Multicomponent reconstructive operations on the mitral valve].

Between 1978 and 1990, 134 reconstructive operations were conducted on the mitral valve in its predominant incompetence. 50% of patients were related to functional class IV (NYHA), 76.1% had atrial fibrillation. In 44 (32.8%) patients interventions were conducted at the same time on other valves. The valvular disease was caused by rheumatism in 78.3%, congenital pathology in 10.4%, and impaired connective-tissue structure in 10.4% of cases. Hospital mortality was 5.9% (8 patients). Mortality in the group of patients with isolated annulovalvuloplasty was 4.4%. The immediate results were good in 93.3% of patients. The late results were studied in 120 patients during a maximum follow-up period of 12 years. The actuarial survival value by the 12th follow-up year was 83.5%. By that time there was no need for a repeated operation in 88.4% of patients, thrombolytic complications did not develop in 91.2% of cases, 96.7% of patients belong to functional classes I and II.

Actuarial Analysis↗

PubMed1991

Synthesis, receptor binding, and tissue distribution of 7 alpha- and 11 beta-substituted (17 alpha,20E)- and (17 alpha,20Z)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17-diols.

The 11 beta-methoxy, 11 beta-ethoxy, and 7 alpha-methyl derivatives of the isomeric (17 alpha,20E)- and (17 alpha,20Z)-(iodovinyl)estradiols 3 and 6, and their no-carrier-added [125I]iodovinyl analogues, were evaluated for their relative target-tissue retention and binding affinity for the estrogen receptor. The isomeric iodovinyl and [125I]iodovinyl derivatives were prepared via destannylation of the corresponding tributylstannyl precursors in the presence of H2O2 or chloramine-T, with retention of configuration. The 20Z isomers 6 exhibited slightly higher receptor binding affinities than the 20E isomers 3, with all eight isomeric products giving relative binding affinity values in the 20-50 range. The 11 beta- and 7 alpha-substituted (iodovinyl)estradiols gave substantially higher estrogen receptor-mediated uterus uptake as compared to the nonsubstituted parent molecule. Synergism between the effect of 11 beta- or 7 alpha-substituents and the configuration of the iodovinyl group was evident from the in vivo distribution pattern of [125I]-3 and -6. The best uterus uptake was observed, at 2 h postinjection, with the 20E isomer of 11 beta-methoxy derivative 3b. However, at 5 h postinjection the 20Z isomer 6b reached higher uterus concentrations than the 20E isomer 3b, and furthermore, these values are now comparable to those observed with the 20Z isomer of the 11 beta-ethoxy derivative 6c. In the case of the 7 alpha-methyl derivatives the differences in in vivo stability between the 20E and 20Z isomers was less pronounced, whereas the 20Z isomer 6d reached somewhat higher uterus to blood as well as nontarget ratios.

Animals↗

PubMed1991

Simplified determination of antipyrine clearance by liquid chromatography of a microsample of saliva or plasma.

We describe a simplified and rapid liquid chromatographic determination of antipyrine clearance (CLAP) calculated from peak height ratios of drug/internal standard. Saliva or plasma was collected 24 hr after the oral administration of 1 g of antipyrine to the subject. A 25-microliter aliquot of the sample is deproteinized with acetonitrile containing 3-nitrophenol (internal standard) and injected into a radial compression module equipped with a 10-micron, 8 mm x 10-cm C18 cartridge, using a 0.025 M aqueous solution of sodium acetate and acetonitrile (88.5:11.5). The minimum measurable concentration was 0.2 microgram/ml. The obtained CLAP values in five healthy subjects and five patients with chronic liver disease coincided well (r greater than 0.9994) with those generated by the use of an established method. The antipyrine clearance in the healthy subjects ranged from 2.203 to 5.721 liters/hr, while in patients with chronic liver disease it was significantly (P less than 0.0027) less (range, 0.544 to 1.103 liter/hr). We also determined antipyrine clearance in two of these subjects given lower doses of this drug and found that the dose has no significant impact on this parameter.

Antipyrine↗

PubMed1991

Sulfonated phthalimidomethyl aluminum phthalocyanine: the effect of hydrophobic substituents on the in vitro phototoxicity of phthalocyanines.

The photocytotoxicity of sulfonated phthalimidomethyl aluminum phthalocyanine, a more hydrophobic photosensitizer as compared to phthalocyanine substituted with sulfonate groups only, was investigated. Inclusion of 1-2 phthalimidomethyl groups into disulfonated aluminum phthalocyanine, resulted in increased partition coefficients between n-octanol and water, and a six-fold increase in both cellular uptake and photocytotoxicity towards Chinese hamster lung fibroblast cells (line V-79). Reducing the number of phthalimidomethyl groups, or increasing the degree of sulfonation, lead to a decrease in the partition coefficient, cellular uptake, and phototoxicity. The quantum yield of singlet oxygen was comparable for all dyes tested in this series, indicating that no significant change in this photophysical parameter resulted from phthalimidomethylation. These results suggest that the addition of 1-2 phthalimidomethyl groups to disulfonated aluminum phthalocyanine improves cellular uptake, but, as the relative efficiency of cell killing was not effected, the intracellular distribution on photosensitive molecules may not be modified.

Animals↗

PubMed1991

Methylxanthines block antigen-induced responses in RBL-2H3 cells independently of adenosine receptors or cyclic AMP: evidence for inhibition of antigen binding to IgE.

Activation of a novel adenosine receptor in a rat tumor mast cell line (RBL-2H3 cells) elicits a transient generation of inositol 1,4,5-trisphosphate and an equally transient increase in the level of free cytosol Ca++: Such responses promote little exocytosis, but markedly enhance the secretory response to antigen. A variety of xanthine adenosine receptor antagonists did not suppress the responses to the adenosine analog 5-N-ethylcarboxamidoadenosine. However, 3-isobutyl-1-methylxanthine (IBMX) and certain related xanthines inhibited antigen (dinitrophenylated bovine serum albumin, DNP-BSA)-induced generation of inositol phosphates, the increase in level of free cytosolic Ca++ and exocytosis in RBL-2H3 cells that were primed with a monoclonal DNP-specific immunoglobulin E (from hybridoma H1 DNP-epsilon-26.82). The same compounds inhibited the binding of antigen to cell attached DNP-specific IgE in a highly selective manner. Incorporation of an aromatic or cycloalkyl group in the 8-position of IBMX or theophylline, for example, resulted in compounds that were more potent inhibitors than the parent compounds. Conversely, substituents in the 7- or 9-position of IBMX resulted in inactive compounds. 1,3-Diethylxanthine and 1,3-dipropylxanthine had no activity, suggesting that substituents as large as ethyl or propyl are not tolerated at the 1-position. Inhibition by IBMX was not observed when cells were activated by nonimmunological stimulants or when cells were primed with certain other monoclonal preparations of DNP-specific IgE and stimulated by DNP-BSA.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

PubMed1991

GTP-binding protein G alpha Z: its down-regulation by dexamethasone and its credentials as a mediator of antigen-induced responses in RBL-2H3 cells.

We have investigated the possible role of guanine nucleotide-binding proteins in the process of antigen-induced exocytosis in a cultured rat mast cell line, RBL-2H3 cells. The mRNAs for the alpha subunits of the guanine nucleotide-binding proteins G alpha S (short and long forms), G alpha i-2, G alpha i-3, and G alpha Z were detected by hybridization with G alpha-specific oligonucleotide probes. The corresponding proteins were identified in membranes of RBL-2H3 cells on the basis of size, immunoreactivity with specific antibodies, and their ability to serve as substrates for ADP-ribosylation by cholera toxin or pertussis toxin. Treatment of cells with as little as 10(-9) to 10(-7) M dexamethasone markedly decreased the amount of G alpha Z mRNA and membrane G alpha Z, as well as the responsiveness of the cells to antigen stimulation. In the same cells, the exposure to dexamethasone caused an increase in the amounts of certain other G alpha subunits, particularly G alpha i-3, and in the responsiveness of the cells to an adenosine analog, N(ethylcarboxamido)-adenosine. Because of the apparent decrease in G alpha Z mRNA and protein in dexamethasone-treated cells and the fact that neither cholera toxin nor pertussis toxin inhibits the stimulatory signals to antigen [J. Biol. Chem. 265:745-753 (1990)], we suggest that G alpha Z is a potential candidate for regulating the early signals in antigen-stimulated RBL-2H3 cells.

Adenosine Diphosphate↗

PubMed1990

On the mechanism of action of dexamethasone in a rat mast cell line (RBL-2H3 cells). Evidence for altered coupling of receptors and G-proteins.

Prolonged exposure of rat basophilic leukemia (RBL-2H3) cells, a cultured analog of rat mast cells, to 0.1 microM dexamethasone resulted in global suppression of various stimulatory events in response to Ag and a global enhancement of the same stimulatory events to the adenosine analog, N-(ethylcarboxamide)adenosine (NECA). We had previously shown that Ag and NECA both activate phospholipase C but by different mechanisms; cells that had been treated with cholera or pertussis toxin, for example, responded to Ag but not to NECA with the release of inositol phosphates, increase in levels of cytosolic Ca2+, and secretion. Because the toxins still inhibited the responses to NECA in dexamethasone-treated cells, the effects of dexamethasone may have been exerted at the level of receptor/G-protein coupling rather than at the level of effector systems. Additional evidence for this was the following: 1) NECA-induced hydrolysis of the inositol phospholipids was still enhanced after permeabilizing (with streptolysin O or Staphylococcus alpha-toxin) and washing the cells; 2) the response to the G-protein stimulant, guanosine 5'-(3-O-thio)triphosphate was also enhanced in permeabilized, dexamethasone-treated cells and 3) binding and kinetic studies suggested that the enhanced responsiveness to NECA was attributable in part to an increase in receptor number. The suppressive action of dexamethasone on Ag-induced hydrolysis of inositol phospholipids, however, was readily lost by permeabilizing RBL-2H3 cells. The results indicate, therefore, that treatment with dexamethasone leads to changes in receptor-coupling mechanisms that are either resistant to (i.e., NECA-mediated responses) or reversed by (i.e., Ag-mediated responses) cell permeabilization.

Adenosine↗

PubMed1990

Activation of phospholipase C via adenosine receptors provides synergistic signals for secretion in antigen-stimulated RBL-2H3 cells. Evidence for a novel adenosine receptor.

5'-(N-Ethyl)carboxamidoadenosine (NECA), an analog of adenosine, transiently stimulated a rat tumor mast cell (RBL-2H3 cells) to cause a release of inositol phosphates and an increase in levels of Ca2+ in the cytosol. It failed, however, to stimulate a sustained uptake of 45Ca2+ or secretion. The effects of other agents that act on P1- or P2-purinergic receptors suggested that NECA and other adenosine agonists acted via a novel subtype of adenosine membrane receptor. Although the order of potency of agonists was characteristic of A2-adenosine receptors, there was no indication of the involvement of adenylate cyclase, and antagonists such as isobutylmethylxanthine, 8-phenyltheophylline, and 8-p-sulfophenyltheophylline inhibited the responses to either NECA or antigen. The fact that stimulation of inositol phospholipid hydrolysis by NECA in washed, permeabilized RBL-2H3 cells was blocked by pertussis toxin as well as by cholera toxin suggested instead that the NECA-sensitive receptor activated phospholipase C via a G-protein. In contrast to NECA, antigen stimulation resulted in a pertussis toxin-resistant, sustained hydrolysis of inositol phospholipids, increases in free intracellular Ca2+, accelerated influx of 45Ca2+, and secretion from RBL-2H3 cells. In combination with NECA, all responses to antigen were markedly enhanced, and the enhancement was selectively blocked by pertussis toxin. The ability of antigen, but not NECA, to provoke secretion may be dependent primarily on the sustained activation of a cholera toxin-sensitive Ca2+ influx pathway that serves to amplify stimulatory signals for secretion. These studies also suggested that phospholipase C could be activated through different G-proteins via different receptors within the same cell.

Adenosine↗

PubMed1990

Biological activities of phthalocyanines. XII: Synthesis tumor uptake and biodistribution of 14C-labeled disulfonated and trisulfonated gallium phthalocyanine in C3H mice.

The biodistribution and metabolism of 14C-labeled disulfonated and trisulfonated gallium phthalocyanine (Ga-PcS) was studied in radiation-induced fibrosarcoma tumor-bearing C3H mice. The [14C]Ga-PcS compounds were prepared via the condensation of [14C]phthalic acid and sulfophthalic acid in the presence of gallium chloride and characterized by their spectroscopic and chromatographic properties. The tissue concentrations of the dyes was measured by scintillation counting of the 14C and by extraction and fluorescence measurements. Elevated dye levels were found in the liver, lungs, kidneys and spleen as well as in the tumor. Lower sulfonation of Ga-PcS favored liver and spleen uptake whereas higher dye sulfonation resulted in greater kidney uptake. Both dyes showed high tumor uptake with peak concentrations exceeding those of most tissues except for the liver in the case of Ga-PcS2. The highest tumor uptake was observed with Ga-PcS3. Both dyes were slowly excreted from the body. The liver-feces pathway was favored in the case of Ga-PcS2 with high activities persisting in the liver, even after 21 days. The Ga-PcS3 was preferentially excreted via the kidney-urine pathway. High performance liquid chromatography analysis of the liver and tumor extracts of [14C]Ga-PcS3-treated animals did not reveal desulfonation of the dye. However, urine analysis showed the presence of radioactive metabolites lacking the characteristic phthalocyanine absorption.

Animals↗

PubMed1990

Biological activities of phthalocyanines--XI. Phototoxicity of sulfonated aluminum naphthalocyanines towards V-79 Chinese hamster cells.

The phototoxicity of sulfonated aluminum naphthalocyanines towards V-79 Chinese hamster cells is investigated. The disulfonated naphthalocyanine exhibits similar photostability, but better cell penetrating properties than the tetrasulfonated dyes. The capacity of the naphthalocyanines to generate singlet oxygen is comparable to that of the corresponding phthalocyanines. However, in contrast to the phthalocyanine dyes, the sulfonated aluminum naphthalocyanines show very little phototoxicity towards the V-79 cells, suggesting close association with non-vital cell constituents or extensive formation of photoinactive adducts and aggregates.

Aluminum↗

PubMed1989

Studies of protein kinase C in the rat basophilic leukemia (RBL-2H3) cell reveal that antigen-induced signals are not mimicked by the actions of phorbol myristate acetate and Ca2+ ionophore.

Exogenous activators of protein kinase C such as PMA in combination with a Ca2+ ionophore (A23187), cause secretion in rat basophilic (RBL-2H3) cells,but they do so through stimulatory signals that are not the same as those generated by Ag or oligomers of IgE. On the one hand, the synergy between PMA and A23187 and the suppression of Ag-mediated signals (hydrolysis of inositol phospholipids and rise in concentration of cytosolic Ca2+) by PMA were totally dependent on protein kinase C. The loss of synergistic and inhibitory actions of PMA, for example, correlated with the loss of protein kinase C (as determined by immunoblotting techniques) when cells were continuously exposed to PMA. Furthermore, the permeabilization of RBL-2H3 cells resulted in the loss of both protein kinase C and the inhibitory action of PMA, but both were retained if cells were exposed to PMA before permeabilization Ag-induced secretion, on the other hand, was not as dependent on the presence of protein kinase C. The potent inhibitor of this enzyme, staurosporine, which blocked completely the secretory response to the combination of PMA and A23187, did not inhibit Ag-induced secretion except at concentrations (greater than 10 nM) that inhibited Ag-stimulated hydrolysis of inositol phospholipids as well. Also RBL-2H3 cells still showed some secretory-response (approximately 25% of normal) to Ag when cells were depleted (greater than 98%) of protein kinase C by prolonged treatment with PMA. Previous studies have indicated that the secretory response to PMA and A23187 is much lower than that elicited by Ag when the concentrations of stimulants were matched to give the same increase in concentrations of cytosolic Ca2+.

Alkaloids↗

PubMed1989

The rise in concentration of free Ca2+ and of pH provides sequential, synergistic signals for secretion in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells.

Ag stimulation of rat basophilic leukemia (RBL-2H3) cells results in hydrolysis of inositol phospholipids, a transient increase in concentration of cytosol Ca2+ [( Ca2+]i), a gradual increase in cytosolic pH (pHi) and the activation of protein kinase C. To determine whether all these changes serve as signals for secretion, studies were conducted with cells permeabilized with streptolysin O in which pHi and [Ca2+]i could be varied independently of each other and enzyme activities could be manipulated. At resting pHi (approximately 7.0) and [Ca2+]i (0.1 microM), the permeabilized cells showed little secretory response to Ag. At resting pHi, elevated levels of Ca2+ (0.33 microM) were required for maximal secretory response to Ag. At a pHi of 7.4, however, 0.1 microM [Ca2+]i was sufficient to sustain near maximal responses to Ag. Therefore, a small increase of [Ca2+]i to 0.33 microM was required to initiate secretion, but once the pHi was elevated secretion could be sustained at near basal levels of [Ca2+]i. Since elevating the [Ca2+]i and pHi, by themselves promoted little secretion, another potentiating signal must have been generated by antigen stimulation. This signal was possibly transduced via hydrolysis of inositol phospholipids and protein kinase C. Even with an elevated [Ca2+]i (0.33 microM) the hydrolysis of the phospholipids and secretion stimulated by Ag were inhibited by guanosine 5'(2-O-thio)diphosphate and neomycin. Furthermore, both protein-kinase C and the secretory response to Ag were lost after permeabilized cells were washed but both were retained if cells were exposed to PMA before permeabilization.

Animals↗

PubMed1989

Receptor-mediated release of inositol 1,4,5-trisphosphate and inositol 1,4-bisphosphate in rat basophilic leukemia RBL-2H3 cells permeabilized with streptolysin O.

Antigen-mediated exocytosis in intact rat basophilic leukemia (RBL-2H3) cells is associated with substantial hydrolysis of membrane inositol phospholipids and an elevation in concentration of cytosol Ca2+ ([ Ca2+i]). Paradoxically, these two responses are largely dependent on external Ca2+. We report here that cells labeled with myo-[3H]inositol and permeabilized with streptolysin O do release [3H]inositol 1,4,5-trisphosphate upon stimulation with antigen or guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) at low (less than 100 nM) concentrations of free Ca2+. The response, however, is amplified by increasing free Ca2+ to 1 microM. The subsequent conversion of the trisphosphate to inositol 1,3,4,5-tetrakisphosphate is enhanced also by the increase in free Ca2+. Although [3H]inositol 1,4,5-trisphosphate accumulates in greater amounts than is the case in intact cells, [3H]inositol 1,4-bisphosphate is still the major product in permeabilized cells even when the further metabolism of [3H]inositol 1,4,5-trisphosphate is suppressed (by 77%) by the addition of excess (1000 microM) unlabeled inositol 1,4,5-trisphosphate and the phosphatase inhibitor 2,3-bisphosphoglycerate. It would appear that either the activity of the membrane 5-phosphomonoesterase allows virtually instantaneous dephosphorylation of the inositol 1,4,5-trisphosphate under all conditions tested or both phosphatidylinositol 4-monophosphate and the 4,5-bisphosphate are substrates for the activated phospholipase C. The latter alternative is supported by the finding that permeabilized cells, which respond much more vigorously to high (supraoptimal) concentrations of antigen than do intact RBL-2H3 cells, produce substantial amounts of [3H]inositol 1,4-bisphosphate before any detectable increase in levels of [3H]inositol 1,4,5-trisphosphate.

Animals↗

PubMed1989

Distribution of haptoglobin phenotypes in oesophageal and gastric cancer.

Haptoglobin (Hp) phenotypes were studied in 72 oesophageal and 104 gastric cancer patients and compared with 100 healthy controls to see if there is any association between oesophageal and gastric cancer and haptoglobin type. There was a significantly increased frequency of Hp 2-1 (59.7%) and Hp 2-2 (91.3%) in oesophageal and gastric cancer patients. Our results suggest that genetic factors play a role in the aetiology and pathogenesis of gastrointestinal tract malignancy.

Esophageal Neoplasms↗