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Biomedical subjects

H Salem

Publications and source records attributed to H Salem.

At least 19 recordsLinked to original sources
PubMed1994

VQLM: a Visual Query Language for Macromolecular structural databases.

Databases of macromolecular structures allow researchers to identify general principles of molecular behavior. They do this by providing a variety of data obtained under a number of different experimental conditions. Many new tools have been developed recently to aid in exploratory analysis of structural data. However, some queries of interest still require considerable manual filtering of data. In particular, studies attempting to make generalizations about complex arrangements of atoms or building blocks in macromolecular structures cannot be approached directly with existing tools. Such studies are frequently carried out on only a few structures or else require a labor-intensive process. To address this problem, we have developed a visual language, VQLM (Visual Query Language for Macromolecules). A query is formulated in this language by drawing an abstract picture of substructures to be searched for in the database and specifying constraints on the objects in them. To illustrate the usefulness of our language, we show how to encode a number of queries that were found scientifically interesting in the published literature in molecular biology. VQLM relies on VQL, a new database language, as its underlying engine for database retrieval and computation. We believe that VQLM will make macromolecular structural data more accessible to scientists, enabling faster and deeper data analysis.

Animals↗
PubMed1992

Autoantibodies to thrombomodulin: development of an enzyme immunoassay and a survey of their frequency in patients with the lupus anticoagulant.

In order to investigate the possibility that autoantibodies to thrombomodulin (TM) may exist in patients with the lupus anticoagulant (LA) and perhaps be implicated in the pathogenesis of recurrent thrombosis seen in such patients, we developed an enzyme-immunoassay to screen serum samples for anti-human TM activity. The major technical problem encountered in developing this assay was to reduce the non-specific binding of serum components from both the LA positive and the negative population. Considerable reduction of non-specific binding was achieved by use of a phosphate/citrate buffer at pH 8.0 and the use of an optimal sample dilution of 1/40. In addition, samples were always tested in parallel in blank wells and results are expressed as an OD ratio. Samples from 113 patients with the LA were assayed and compared to 78 patients referred for LA testing but found to be negative. The mean OD values for the LA positive patients (+/- SD) was 1.36 (0.44) with a range of 0.78-2.57. This was virtually identical to the values for the LA negative population (1.38 +/- 0.40, range 0.76-2.77). The results of this study indicate that there is no evidence for the presence of a significant autoantibody activity to TM in patients with the LA when compared to LA negative patients. If such autoantibodies do exist their frequency must be quite low.

Autoantibodies↗
PubMed1992

Tumor necrosis factor production during human renal allograft rejection is associated with depression of plasma protein C and free protein S levels and decreased intragraft thrombomodulin expression.

Fibrin deposition is a common accompaniment of renal allograft rejection, indicating disruption of the normal physiologic balance between procoagulant and anticoagulant pathways. In vitro, tumor necrosis factor (TNF) induces endothelial expression of the procoagulant, tissue factor, and downregulation of thrombomodulin, a key component of the thrombomodulin/protein C (PC)/protein S (PS) pathway, which normally maintains an anticoagulant state by inactivating thrombin, preventing further thrombin formation by degrading factors Va and VIIIa, and decreasing plasminogen activator inhibitor activity. Raised levels of TNF were recently demonstrated within the blood of patients during episodes of renal allograft injection, and may be an early and discriminatory marker of rejection. This led us to investigate prospectively whether monitoring of serum TNF levels was of value clinically, and was associated with effects on circulating PC and PS levels, or alterations in intragraft thrombomodulin expression. Plasma samples (n = 454) were collected three times/week from all patients (n = 25) undergoing renal transplantation during a 9-month consecutive period, and assayed by ELISA and functional assays for TNF, PC, and free PS (FPS). Portions of renal biopsies, taken to evaluate episodes of acute deterioration of renal function, were evaluated by immunoperoxidase labeling for the presence and distribution of TNF, thrombomodulin, PC, PS, thrombin, fibrin, and factors V and VIII. Comparison of 78 plasma samples collected during 26 episodes of biopsy-proven acute cellular rejection with samples collected during periods of stable renal function (n = 349) showed that TNF levels rose significantly (390 +/- 242 pg/ml, p less than 0.01) above background levels 3 days before rising serum creatinine concentrations, and peaked (2,426 +/- 978 pg/ml) on the day of clinical rejection. PC-antigen (Ag) concentrations also decreased 3 days before rejection (68 +/- 13%, p less than 0.05), and were maximally depressed (49% +/- 16%, p less than 0.001) on the day of rejection. FPS levels were normal until the day before rejection (63% +/- 8%, p less than 0.01) and, like PC, were maximally depressed (43 +/- 10%) at rejection. Plasma TNF levels were significantly and inversely correlated with PC-Ag (p less than 0.001) and FPS (p less than 0.005) levels during rejection, regardless of whether such rejection episodes were steroid responsive or required OKT3 monoclonal antibody therapy. TNF, PC, and FPS levels were normal during episodes of cyclosporine toxicity and viral infection.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers↗
PubMed1992

Inhalation toxicity of chromium from Whetlerite dust in rats.

The acute inhalation toxicity and metabolic fate of chromium and copper from Whetlerite dust in rats were investigated. Groups of male and female, Sprague-Dawley rats were exposed to Whetlerite dust and base carbon dust as outlined in the OECD Limit Test guidelines. At 14, 28 and 180 days post-exposure, rats were evaluated for gross pathological changes and tissues were collected for chromium and copper determination. Four deaths occurred during or post-exposure, but did not appear to be compound related. No gross pathological changes were observed at necropsy in either group. Organ chromium concentrations were below detection limits of 0.5 micrograms Cr/g dry tissue in both exposure groups. According to OECD guidelines, neither Whetlerite dust nor base carbon dust demonstrated an acute inhalation toxicity.

Administration, Inhalation↗
PubMed1989

Inorganic chemistry of chromium and its speciation in Whetlerite.

Chromium compounds are among the impregnants that enhance the ability of carbon air filters to absorb and destroy toxic agents such as CK and AC. The possibility of inhaling chromium-containing carbon dust from such filters has caused concern because, in addition to being an essential nutrient, chromium has been identified as a chemical carcinogen in humans. The essentiality or carcinogenicity of chromium depends upon its chemical speciation. Solubility and oxidation state are particularly important factors in assessing the potential hazards associated with the possible inhalation of chromium-containing dusts from these impregnated carbons or Whetlerites. The chemical speciation of the chromium in Whetlerite was found to be: from 0.6 to 1.3% insoluble trivalent chromium; from 1.0 to 1.3% insoluble hexavalent chromium; and from 0.7 to 0.9% soluble hexavalent chromium. The impregnation process, and the resulting speciation of chromium in Whetlerite, is consistent with the inorganic chemistry of chromium.

Air Pollutants, Occupational↗
PubMed1989

Speciation, bioavailability, and systemic distribution of chromium from Whetlerite dust.

Exploratory studies were conducted to determine if chromium from Whetlerite dust is bioavailable when administered intratracheally to rats, and if so, to determine its speciation. These studies indicated that chromium in this form and by this route of administration was bioavailable and was found in the trivalent state only. Less than 25% of the administered dose was recovered after 4 h, suggesting that most of the chromium was rapidly absorbed, distributed, and eliminated. Most of the chromium was found in the lungs and kidneys. The time course in the kidney suggests that this organ may be involved in the metabolism and elimination of trivalent chromium. Unexpected mortality in the experimental group of rats may have been due to the copper content of the Whetlerite, which exceeded the LD50 in the dose administered.

Animals↗
PubMed1986

Pharmacokinetics of oral contraceptive steroids in Egyptian women: studies with Ovral, Nordette and Norminest.

Plasma concentration profiles and pharmacokinetic parameters have been obtained following single dose administration of three commonly used oral contraceptive steroid preparations, Ovral, Nordette and Norminest to Egyptian women. The constituents of the preparations are as follows: Ovral (50 micrograms ethinyloestradiol, EE2 and 500 micrograms levonorgestrel, LNG); Nordette (30 micrograms EE2 and 150 micrograms LNG); and Norminest (35 micrograms EE2 and 500 micrograms norethisterone, NOR). Peak plasma concentrations of EE2 ranged between 116-160 pg ml-1 for Ovral, 55-78 pg ml-1 for Norminest and 30-70 pg ml-1 for Nordette. There was no significant difference in half-life (t1/2), oral clearance (CL) or apparent volume of distribution (Vd). The relative values of the area under the plasma concentration-time curve (AUC) reflected well the different amounts of oestrogen in each preparation. There was no significant difference in t1/2, CL or Vd for LNG in the 2 preparations containing this progestogen. The mean AUC following Nordette (150 micrograms LNG) was 40% of that following Ovral (500 micrograms LNG; p less than 0.001). Comparing pharmacokinetic parameters for the same dose of LNG (Ovral) and NOR (Norminest) showed the AUC to be decreased and CL and Vd increased in the latter group. The study indicates that the kinetic profile of the OCS in healthy Egyptian women are similar to other ethnic populations.

Adult↗
PubMed1984

A 13-week vapor inhalation study of n-hexane in rats with emphasis on neurotoxic effects.

Male and female Fischer 344 rats were exposed to 0-, 3000-, 6500-, or 10,000-ppm n-hexane vapors 6 hr per day, 5 days per week, for 13 weeks. The 13-week exposures had no adverse effect on the growth of female rats. However, the mean body weight gain of male rats in the 10,000-ppm group was significantly lower than for controls at 4 weeks of exposure and thereafter. In addition to the depression of body weight gain, the male exposed to 10,000 ppm had slightly but significantly lower brain weights at necropsy. No adverse testicular effects were noted. Axonopathy was observed in the tibial nerve in four of five male rats from the 10,000-ppm group and one of five male rats in the 6500-ppm group and in the medulla from one male rat in the 10,000-ppm group. These axonal changes were detectable only in teased nerve fiber preparations or in Epon embedded specimens. Histopathologic studies on Formalin fixed tissues did not reveal any lesions that were attributed to n-hexane exposure.

Air↗
PubMed1983

A comparison of automated data collection and manual data collection for toxicology studies.

Automated data collection was compared with manual data collection in terms of accuracy and man-hours devoted to data manipulation and checking. The comparison was based on experience with an automated data collection system (DOLPHIN)TM1 developed at Toxigenics for use in conducting toxicological studies. It was found that on-line data collection increases the quality of the data gathered because: 1) it facilitates scientific observation by displaying historical data and statistics on changes since the last observation period; 2) it virtually eliminates errors due to oversight and transcription; 3) it allows more careful monitoring of the course of the study by providing immediate access to interim summary statistics; 4) it provides complete documentation of all changes made to the data after initial collection. In addition, automated data collection enables more rapid completion of the final report of results because: 1) fewer departmental transfers are required; 2) auditing by Quality Assurance (Q.A.) personnel is facilitated.

Data Collection↗
PubMed1983

[Effect of autonomic drugs on Na K adenosine triphosphatase activity in the heart and skeletal muscles].

It has been found that ATP-ase activity increases considerably in the heart after intravenous administration of adrenaline, noradrenaline, phenylephrine (50 micrograms/kg), phentolamine, atropine, and also after vagotomy and adrenaline given after vagotomy. In the skeletal muscle ATP-ase activity increases considerably after noradrenaline, isoprenaline, phenylephrine (50 micrograms/kg), adrenaline given after phentolanine and Ach given after denervation of the muscle. A decrease in the activity of the enzyme in the heart was found after propranolol hexamethonium and Ach given after vagotomy, whereas in the skeletal muscle after Ach, hexamethonium and after muscle denervation. No changes or weak actions in the skeleton muscle are evoked by phenylephrine (10 micrograms/kg), propranolol, atropine, tubokurarine as well as adrenaline given after muscle denervation. In the heart, however, isoprenaline, Ach, adrenaline after propranolol, Ach after atropine and Ach after hexamethonium. A very low involvement of the enzyme studied in utilization of ATP reserves in the heart and skeletal muscle was found. However, of significant importance in this process may be the reactions catalized by extramembrane ATP-ases. The autonomic nervous system effects ATP-ase activity, and stimulation of beta-adrenergic receptor causes an increase in the enzyme activity in both muscles, whereas stimulation of the muskarine receptor decreases the enzyme activity in the heart. Moreover, it was found that stimulation of N2 receptor of the motor plate results in increased ATP-ase activity in the skeletal muscle. The present studies have not brought enough evidence accounting for participation of alpha-adrenergic receptor in regulation of the enzyme studied.

Adrenergic beta-Agonists↗
PubMed1980

Beta-thromboglobulin and platelet aggregates in glomerulonephritis.

Circulating platelet aggregate ratios (CPAR) and plasma beta-thromboglobulin (B-TG) concentrations were determined in 53 patients with chronic progressive glomerulonephritis [mesangiocapillary glomerulonephritis (15) and focal and segmental hyalinosis and sclerosis (38)] and compared with those from both normal subjects and patients with no evidence of renal disease. The mean B-TG concentration was higher in patient controls [32.6 +/- 6.2 ng/ml (SEM)] than in normal subjects [19.0 +/- 2.0 ng/ml (SEM)] but this did not reach significance (P < 0.10 > 0.05). Nephritic patients had markedly elevated levels [49.8 +/- 4.0 ng/ml (SEM)], but B-TG was significantly correlated with renal impairment. Elevated B-TG levels in patients with nephritis may thus reflect renal impairment or ill-health. The mean CPAR of the nephritic patients [0.75 +/- 0.02 (SEM)] was lower than that of both normal [0.86 +/- 0.03 (SEM), P < 0.001] and patient controls [0.87 +/- 0.02 (SEM), P < 0.001]. CPAR was not correlated with renal function or platelet concentration. Low CPAR in nephritic subjects provides further evidence for in-vivo activation of platelets in patients with glomerulonephritis.

Adult↗
PubMed1979

Evaluation of the toxicologic and teratogenic potentials of sodium fluorescein in the rat.

Sodium fluorescein (10%) when injected intravenously (5 ml/kg) in pregnant albino rats crossed the placental barrier and appeared to be distributed throughout the fetus within 15 min. It was detectable in the fetus up to 4 h after injection but not beyond 24 h. A single intravenous administration of sodium fluorescein did not produce embryotoxic or teratogenic effects. Oral LD50 studies using sodium phenobarbital on rats which received sodium fluorescein during their fetal development showed no apparent effects of sodium fluorescein on their drug detoxification systems.

Abnormalities, Drug-Induced↗
PubMed1978

Comparative analgetic testing of various compounds in mice using writhing techniques.

Anti-writhing assays to detect analgesia or specific activity against selected agonists were performed on albino mice. Acetylcholine Cl, bradykinin triacetate, phenylquinone, and serotonin creatinine sulfate were used as agonists. 10 compounds, including 5 standard analgetics, were tested against each agonist. Attempts to study histamine phosphate as an agonist were not successful. Results of these investigations showed satisfactory analgetic acitivity for codeine phosphate and acteyl salicylic acid (ASA) in all assays. weaker analgetics displayed varying degrees of activity depending on the agonist tested. Acute oral toxicities were determined for the 10 test compounds and the analgetic ED50 vs the LD50 of each compound was compared. The data confirmed the nonspecificity for writhing assays as well as a variability in activity of the test compounds against the various agonist.

Acetylcholine↗