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Biomedical subjects

M Khalil

Publications and source records attributed to M Khalil.

At least 55 records · Page 3Linked to original sources
PubMed1996

Human plasma patterns during 14 days ingestion of vitamin E, beta-carotene, ascorbic acid, and their various combinations.

OBJECTIVE: We wanted to learn about plasma patterns of ascorbic acid (AA), beta carotene (BC), and vitamin E (vit E) when each or their various combinations were fed to humans. Conceivably, the combined absorption of these antioxidants could synergize maximum plasma redox potential. METHODS: Vit E (800 mg/day), BC (30 mg/day), and AA (1000 mg/day) were fed individually or in various combinations with each other to 91 volunteers divided into different feeding groups for 14 days. Plasma vit E, carotenes, and AA patterns were analyzed by standardized methods; values were compared with each group's baseline value. RESULTS: AA feeding did not significantly increase already saturated plasma AA concentrations above baseline. Intake of BC did not influence vitamin A (vit A) levels. Feeding of only vit E or only BC, with or without AA addition, or a combination of BC and vit E significantly increased plasma vit E and carotene levels after 2 days. A statistically (ANOVA) significant increase in plasma vit E above baseline was noted when vit E was ingested combined with AA or BC; this increase in plasma vit E was not significant when AA, BC and vit E were taken in combination. CONCLUSION: Our results show that BC or AA ingestion in combination with vit E significantly increases circulating vit E above that seen when vit E is individually ingested. Vit E in combination with BC or AA seems a practical means or increasing the circulating antioxidant potential afforded by vit E. Reasons why such synergism does not exist when an AA, BC, vit E combination is ingested is not yet obvious.

Adult↗
PubMed1996

Characteristic localization of gp130 (the signal-transducing receptor component used in common for IL-6/IL-11/CNTF/LIF/OSM) in the rat brain.

The localization of gp130, the signal transducing receptor component used in common for interleukin (IL)-6, IL-11, ciliary neurotrophic factor (CNTF), LIF and OSM, in the rat brain was demonstrated by immunohistochemistry using an antibody specific to gp130. The gp130 immunoreactivity was observed in both glial and neuronal cells. Two distinct neuronal staining patterns were observed. The first showed neuropil staining, observed mainly in telencephalic structures including the hippocampus, cerebral cortex and caudate-putamen. The second pattern was observed on the cytoplasmic membrane of neuronal somata and was found primarily in the lower brainstem, in the large neurons of the reticular formation, and in spinal and cranial motor neurons. Electron-microscopic analysis revealed that both types of gp130 immunoreactivity were primarily associated with the cytoplasmic membrane and were not localized exactly at synaptic sites. Further, gp130 immunoreactivity was also observed in the oligodendrocytes and subependymal zone. These widespread but characteristic patterns of gp130 immunoreactivity overlap well with those of IL-6 receptor and CNTF alpha chains, suggesting a role of cytokines and growth factors such as IL-6 and CNTF via gp130 in certain specific regions of the brain.

Amino Acid Sequence↗
PubMed1995

The role of bronchodilators in the management of bronchiolitis: a clinical trial.

A randomized clinical trial was conducted on young children with bronchiolitis admitted to hospital with moderate illness to determine the efficacy of the bronchodilators Salbutamol and ipratropium bromide, either as a single drug or in combination, given as a nebulized solution, compared with a normal saline placebo. Eighty-nine patients, aged from 23 days to 11 months, were randomized into four groups, depending on administered drug or placebo, as follows: group 1--Salbutamol (n = 20); group 2--ipratropium bromide (n = 23); group 3--combined Salbutamol and Ipratropium bromide (n = 24); group 4--normal saline (n = 22). The groups were identical with respect to age, sex, family history of atopy, respiratory syncytial virus (RSV) positivity and enrollment score. They were scored using the clinical parameters of wheezing, retractions and respiratory rate at enrollment, at 30 and 60 minutes after the first nebulization, and after 60 minutes following completion of subsequent nebulization at 6, 12, 24 and 36 hours. We did not find any significant difference in the rate of improvement and the final score (p = 0.49) in the four groups. The same finding was also noted in children aged more than 3 months (p = 0.35) and in those positive for RSV infection (p = 0.18). The lengths of hospitalization in the four groups were also similar (p = 0.79). It is concluded that there is no role for the nebulized bronchodilators Salbutamol and Ipratropium bromide, either as a single agent or in combination, compared with normal saline placebo in treating young children in hospital with bronchiolitis.

Administration, Inhalation↗
PubMed1995

Comparison of duration of neuromuscular blocking effect of atracurium and vecuronium in young and elderly patients.

In a controlled, randomized study, we evaluated duration of neuromuscular block in 80 patients undergoing routine abdominal surgery. Forty patients were aged 18-50 yr (control group) and 40 patients were more than 65 yr (elderly group). All patients had normal plasma creatinine concentrations. After induction of anaesthesia, patients were allocated randomly to receive either atracurium 0.5 mg kg-1 or vecuronium 0.1 mg kg-1 to facilitate tracheal intubation. Monitoring of the evoked response of the adductor pollicis muscle to supramaximal single twitch ulnar nerve stimulation every 10 s was performed and measured with a strain gauge. Repeat doses of atracurium 0.1 mg kg-1 or vecuronium 0.02 mg kg-1 were administered when the adductor pollicis response recovered to 25% of the control twitch height. We found that the duration of action of the initial dose of atracurium was similar in the control and elderly groups, and it did not vary after repeated doses. However, the initial dose of vecuronium caused a significantly longer period of clinical block in the elderly group compared with the controls, and the duration of action of repeated doses was longer in the elderly group. We conclude that as there is a risk of prolonged effect of vecuronium in the elderly, monitoring of neuromuscular function is recommended in this group. Alternatively, atracurium should be preferred for prolonged surgery in elderly patients.

Abdomen↗
PubMed1994

Biochemical characterization of yeast RAS2 mutants reveals a new region of ras protein involved in the interaction with GTPase-activating proteins.

We report biochemical characterization of two recently identified mutants of yeast RAS2, RAS2-E99K and RAS2-E130K. These mutants exhibit dominant activating phenotypes in yeast. Characterization of their intrinsic GTPase and GDP dissociation as well as their ability to stimulate adenylate cyclase showed that these activities of RAS2-E99K mutant protein were similar to those of the wild type protein. RAS2-E130K protein, on the other hand, differed from the wild type protein with a fast GDP dissociation rate and 2-fold higher activation of adenylate cyclase. When the sensitivity to GTPase-activating protein (GAP) was examined, we found that the RAS2-E99K protein was approximately 1200-fold less sensitive to NF1-GAP activity. In addition, the affinity for NF1 as revealed by competition binding experiments was reduced more than 150-fold with RAS2-E99K protein. Thus, the RAS2-E99K mutation affects interaction with GAP proteins. This mutation is particularly interesting because it is the first mutation identified in the alpha 3 region of ras protein that affects GAP interaction. The alpha 3 region appears to be directly involved in interaction with NF1, since peptides containing the sequence encompassing residue 99 of RAS2 inhibit NF1-GAP activity. These results suggest that the interaction between ras and GAP involves a larger region within ras than previously recognized.

Adenylyl Cyclases↗
PubMed1994

Diarrhoeal disease in children in Gaza.

A 1-year prospective study in Gaza of diarrhoeal disease in children aged < 5 years demonstrated that Salmonella spp. (18.5% of cases), Cryptosporidium (14.6%), Campylobacter spp. (8.3%) and rotavirus (6.8%) were the major pathogens. However, when compared with non-diarrhoeic controls, only Cryptosporidium and rotavirus were significantly associated with diarrhoea. Cryptosporidiosis was found only in children aged < 2 years and significantly more children with cryptosporidiosis were malnourished. This malnutrition may have been due to the infection, since children with cryptosporidiosis tended to have had diarrhoea for relatively long periods prior to admission. It was not possible to distinguish between the different enteropathogens on clinical grounds. However, more children with rotavirus infection vomited and cryptosporidial diarrhoea lasted significantly longer (14.9 days) than rotavirus diarrhoea (5.9 days). Overcrowding was linked with an increased risk of cryptosporidiosis and breast feeding was associated with some protection. Twenty-one of the 29 children who died during the study died with diarrhoea and Cryptosporidium was detected in eight (38%) of these 21 children.

Age Factors↗
PubMed1994

Characterization of glycogen-deficient glc mutants of Saccharomyces cerevisiae.

Forty-eight mutants of Saccharomyces cerevisiae with defects in glycogen metabolism were isolated. The mutations defined eight GLC genes, the function of which were determined. Mutations in three of these genes activate the RAS/cAMP pathway either by impairment of a RAS GTPase-activating protein (GLC1/IRA1 and GLC4/IRA2) or by activating Ras2p (GLC5/RAS2). SNF1 protein kinase (GLC2) was found to be required for normal glycogen levels. Glycogen branching enzyme (GLC3) was found to be required for significant glycogen synthesis. GLC6 was shown to be allelic to CIF1 (and probably FDP1, BYP1 and GGS1), mutations in which were previously found to prevent growth on glucose; this gene is also the same as TPS1, which encodes a subunit of the trehalose-phosphate synthase. Mutations in GLC6 were capable of increasing or decreasing glycogen levels, at least in part via effects on the regulation of glycogen synthase. GLC7 encodes a type 1 protein phosphatase that contributes to the dephosphorylation (and hence activation) of glycogen synthase. GLC8 encodes a homologue of type 1 protein phosphatase inhibitor-2. The genetic map positions of GLC1/IRA1, GLC3, GLC4/IRA2, GLC6/CIF1/TPS1 (and the adjacent VAT2/VMA2), and GLC7 were clarified. From the data on GLC3, there may be a suppression of recombination near the chromosome V centromere, at least in some strains.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1994

Breastfeeding and weaning practices in Saudi Arabia.

A National Child Health Survey was conducted during 1987 for which a stratified multi-stage sampling was done. Out of the 8482 mothers interviewed 6131 had at least one live birth 5 years or less before the survey. Eighty-two per cent of the currently breastfed children, were less than 6 months of age, but only 55 per cent of the infants up to 1 month of age were breastfed without supplementation. The mean interval between supplementation and weaning for all age groups of mothers was 7.7 months. The predominant causes of weaning were child reaching suitable age and mother not having enough milk. This study establishes base line information about feeding practice on a nationwide basis in Saudi Arabia.

Breast Feeding↗
PubMed1994

Pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis.

BACKGROUND: Rocuronium, like other steroidal nondepolarizing muscle relaxants, may in part be eliminated by the liver. To determine the influence of liver disease on its neuromuscular blocking effect, we studied the pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis. METHODS: Eighteen patients undergoing elective surgery, 10 with cirrhosis and 8 with normal liver function, were studied. Anesthesia was induced with intravenous thiopental 5-7 mg.kg-1 and maintained with 60% nitrous oxide in oxygen and repeated doses of fentanyl 2 micrograms.kg-1. The force of thumb adduction in response to supramaximal ulnar nerve stimulation was monitored and recorded. An intravenous bolus of rocuronium 0.6 mg.kg-1 was administered and venous blood sampled at frequent intervals for 6 h. Plasma concentrations of rocuronium was measured by high-pressure liquid chromatography. Data were fitted to both a pharmacokinetic and a pharmacodynamic model by using a two-compartment open model and an effect compartment model. Data were analyzed by least-squares regression. RESULTS: The onset of neuromuscular blockade was longer (P < 0.01) in patients with cirrhosis (158 +/- 56 s) than in normal patients (108 +/- 33 s). Recovery of the thumb twitch to 75 and 90% of its control value was 77 +/- 25 and 88 +/- 29 min in cirrhotic patients versus 57 +/- 11 and 64 +/- 13 min, respectively, in normal patients (P < 0.05). The central volume of distribution of rocuronium was 104 +/- 21 in cirrhotic patients and 78 +/- 24 ml.kg-1 in normal patients (P < 0.05). No significant difference in elimination kinetics was observed between the two groups. The elimination half-life was 87.5 +/- 17.5 min in normal patients and 96.0 +/- 36.8 min in cirrhotic patients (difference not significant). This increased onset time was linearly correlated to the increased central volume of distribution of rocuronium in cirrhosis. CONCLUSION: Rocuronium onset time is longer in cirrhotic patients than in those with normal liver function; this can be explained by an increase in the volume in which rocuronium initially distributes. Although elimination kinetics are unchanged in patients with cirrhosis, rocuronium recovery time is prolonged in cirrhotic patients.

Androstanols↗
PubMed1993

Isolation of human glycogen branching enzyme cDNAs by screening complementation in yeast.

Functional complementation of the Saccharomyces cerevisiae glycogen branching enzyme deficiency was screened to isolate human cDNAs that encode this enzyme. Human hepatoma cell line HepG2-derived cDNA libraries using the pAB23BXN yeast expression vector yielded four cDNAs capable of complementing the glc3::TRP1 glycogen branching enzyme mutation. Complementation was recognized by an altered iodine-staining trait. This illustrates that interspecies complementation can be used to isolate rare plasmids from libraries by screening if there is sufficient resolution. The human and yeast glycogen branching enzymes have a 67% identical amino acid sequence over a major portion of their length. The human gene is on chromosome 3.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1993

Antenatal thrombocytopenia in three patients with TAR (thrombocytopenia with absent radii) syndrome.

Three fetuses with TAR (thrombocytopenia with absent radii) or TAR variant syndrome were found to be thrombocytopenic during the third trimester of the pregnancy. These findings indicate that fetal blood sampling, besides ultrasonography, skeletal radiographs, or even fetoscopy, may indeed contribute to the prenatal diagnosis of TAR syndrome, and thus may help in differentiating TAR syndrome from other syndromes with malformations of the upper limbs.

Abnormalities, Multiple↗
PubMed1993

A syndrome of insulin resistance resembling leprechaunism in five sibs of consanguineous parents.

Leprechaunism is a rare autosomal recessive disorder associated with extreme insulin resistance with paradoxical hypo-glycaemia. It is characterised by prenatal and postnatal growth retardation, reduced subcutaneous tissue, coarse features, acanthosis nigricans, enlarged genitalia, and death in the first year of life. Defects in both the insulin receptor and postreceptor steps of the insulin action pathway have been reported. At the molecular level, several mutations have been described. The patients reported here are from a Yemeni family with a syndrome of insulin resistance similar to leprechaunism in which the parents are second cousins and five of their eight children are affected. However, the phenotypes seem to be less severe than the classical leprechaunism previously described. All the children are alive (oldest 11 years), there is normal subcutaneous tissue, and a normal growth pattern in some of them. It may be that this is a milder type of leprechaunism with a better prognosis, perhaps caused by a different type of mutation from those previously described.

Child↗
PubMed1993

New activated RAS2 mutations identified in Saccharomyces cerevisiae.

Activating mutations in RAS proto-oncogenes encode proteins with greater GTP binding. Such mutant proteins are responsible for many human cancers. Six new amino acids were discovered that can yield an activated Saccharomyces cerevisiae RAS2 protein when they are altered. These new RAS2 alleles were found among a collection of 35 random mutations that exhibit a dominant reduction of glycogen accumulation. The RAS2-P41S and RAS2-E99K alleles encode proteins that have lost responsiveness to GTPase activating proteins. They affect amino acids in loop 2 and helix 3 respectively and illustrate that GTPase activating proteins recognize a larger portion of the RAS structure than previously realized. RAS2 mutations E130K, S153F, A154T, and A157S alter amino acids proximal to the guanine binding site and probably influence nucleotide binding either directly or indirectly.

Alleles↗
PubMed1993

Pharmacokinetics and pharmacodynamics of pipecuronium in patients with cirrhosis.

To determine the effect of liver cirrhosis on the pharmacokinetics and pharmacodynamics of pipecuronium, the authors administered 100 micrograms/kg of pipecuronium intravenously to eight patients with liver cirrhosis and eight patients with normal liver and renal function undergoing elective abdominal surgery. All patients were anesthetized with thiopental (5-7 mg/kg), nitrous oxide (50-70% in oxygen), and fentanyl in repeated doses (2 micrograms/kg). Plasma concentrations of pipecuronium were determined by high-pressure liquid chromatography. A two-compartment open model was used for pharmacokinetic analysis. Thumb-elicited mechanical response to single-twitch ulnar nerve stimulation was also measured. Total plasma clearance did not differ between controls (2.96 +/- 1.05 mL.min-1.kg-1, mean +/- SD) and cirrhotics (2.61 +/- 1.16 mL.min-1.kg-1). Terminal elimination half-life was 111 +/- 46 min in controls and 143 +/- 25 min in cirrhotics. The total apparent volume of distribution at steady state did not differ between controls (350 +/- 81 mL/kg) and cirrhotics (452 +/- 222 mL/kg). The volume of the central compartment was not different between the two groups. The onset of neuromuscular blocking effect was longer in cirrhotics (233 +/- 112 s) (P < 0.05) than in controls (170 +/- 33 s). The clinical duration (injection until single twitch returned to 25%) was similar between the two groups: 167 +/- 41 min in controls and 165 +/- 48 min in cirrhotics. The authors conclude that hepatic insufficiency due to cirrhosis does not alter the pharmacokinetics and pharmacodynamics of pipecuronium (100 micrograms/kg).

Abdomen↗
PubMed1992

Effect of cyclosporine treatment on carnitine and myo-inositol in diabetic rats.

1. The effect of long-term (20 wk) treatment of cyclosporine A (CyA) was studied in urine, blood, liver, kidney and pancreatic concentrations of acid-soluble carnitine and free myo-inositol in streptozotocin diabetic rats. 2. Diabetic rats excreted significantly higher concentrations of carnitine and myo-inositol; CyA prevented the urinary loss of carnitine but not myo-inositol. 3. Blood carnitine levels were not different between normal and diabetic rats, however, CyA significantly decreased these levels. Conversely, blood myo-inositol concentrations were higher in diabetic than in normal rats; CyA prevented this increase. 4. Hepatic concentrations of both carnitine and myo-inositol were increased in diabetic rats; CyA treatment caused even further increase. 5. Pancreas from diabetic rats contained less carnitine and myo-inositol compared to normal pancreas. CyA treatment did not affect pancreatic carnitine, but it normalized myo-inositol in diabetic rats. 6. The kidney carnitine or myo-inositol levels were not influenced either by diabetes or by CyA treatment. 7. These results suggest that CyA treatment causes changes in carnitine and myo-inositol concentrations in biologic fluids and certain tissues.

Animals↗