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Biomedical subjects

M Hafez

Publications and source records attributed to M Hafez.

At least 19 recordsLinked to original sources

[Test schemes for evaluation of the effect of a probiotic feed additive on the gut microflora of young calves and newly hatched turkeys].

Probiotic feed additives have to undergo a strict assessment according to EU regula-tions, including the evaluation of the influence on the gut microflora of the host animal. A probiotic strain of the genus Enterococcus faecium and two different host animal species, young calves and newly hatched turkeys, were chosen as a test model for the establishment of schemes for feeding trials. Investigations included faeces samples and pooled swab samples of faeces as well as samples from gut sections derived from diagnostic slaughtering. The samples were tested for aerobic total count, for enterococci count and for Enterobacteriaceae and E. coli. The test schemes were appropriate for the evaluation of the influence of the probiotic feed additive on the physiological gut microflora of the host animals. Additional information could be gathered concerning safety aspects and effectiveness.

Animal Feed↗

Reconstructive surgery in spinal tumours.

AIMS: This study reports 21 patients who underwent reconstructive surgery for destructive spinal tumours. MATERIALS AND METHODS: The mean age was 49 years (range: 39-71 years). Primary lesions were met in two cases. Secondary spinal tumours were diagnosed in 19 cases. Thirteen were breast carcinoma metastases (61.9%). The cervical spine was involved in four cases, thoracic spine in six cases, and the lumbar spine in 11 cases. One patient underwent decompression laminectomy and posterior pedicle screw stabilization. The others underwent tumour tissue excision, with spinal reconstruction with autogenous bone grafting, with or without vertebral body replacement prosthesis. Anterior and posterior stabilization of the vertebral column was also used. RESULTS: The objectives of surgery were achieved, in that early ambulation, easier nursing care, pain relief and neurological recovery were reported in all cases. No surgery-related complications were encountered. CONCLUSIONS: We recommend surgical intervention for such lesions where reasonable longevity is anticipated.

Adult↗

Hepatocellular carcinoma in Egyptians with and without a history of hepatitis B virus infection: association with hepatitis C virus (HCV) infection but not with (HCV) RNA level.

The aim of this study was to analyze the association of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) in Egypt, using hepatitis B virus (HBV) and hepatitis E virus (HEV) as virus controls. In addition, the association of HCC with HCV RNA levels among persons seropositive for HCV was analyzed. We compared 131 patients with proven HCC, 247 with bladder cancer, and 466 healthy hospital employees. Age, sex, and place of residence were recorded to study confounding factors. Among the healthy controls, 16% were seropositive for HCV, 21% for HBV, and 31% for HEV. When healthy controls were age-matched with HCC patients, the latter were significantly (P < 0.001) more often HCV seropositive (67%) than were the controls (30%). The seropositivity for HBV and HEV did not differ significantly in frequency between the two groups. The seropositivity for HCV was also significantly (P < 0.001) more often found in HCC patients (76%) than in BC patients (47%), with seroprevalences for HBV and HEV not differing significantly in these age-matched groups. In HBV-negative HCC and bladder cancer patients, seroprevalence for HCV was significantly (P = 0.002) higher in HCC patients (68%) than in bladder cancer patients (36%). This difference was even more pronounced (P < 0.001) in HBV-positive HCC and bladder cancer patients (78% versus 52%, respectively). Of HCV-seropositive individuals, 49% were HCV RNA positive by branched DNA assay, and of these, 96% were infected by HCV genotype 4. No correlation between HCV RNA load and seropositivity of HBV or age or disease state was found. Infection with HCV and HCV-HBV double infection, but not HBV or HEV infection alone, is strongly correlated with HCC in Egypt.

Adolescent↗

Human Prop-1: cloning, mapping, genomic structure. Mutations in familial combined pituitary hormone deficiency.

Prop-1 is a newly isolated pituitary-specific paired-like homeodomain transcription factor whose cDNA sequence is well known in mouse. To study its involvement in human combined pituitary hormone deficiency (CPHD), we have isolated the human cDNA ortholog and determined the exon/intron organization and chromosomal localization of the human gene. A Prop-1 defect was characterized in three CPHD families. One missense mutation (R73C) involves a residue conserved in 95% of the more than 400 homeodomain proteins so far identified; in vitro splicing assays demonstrated the functional importance of the second defect, whereas the remaining mutation is a frameshift. Given the disease phenotype documented in the patients, these data, which will facilitate molecular investigations in other patients, demonstrate the crucial role of Prop-1 in the proper development of somatotrophs, lactotrophs, thyreotrophs and gonadotrophs.

Amino Acid Sequence↗

Purification and characterization of the glucoamylase produced by a strain of Aspergillus flavus.

A strain of Aspergillus flavus isolated from an agricultural soil in Egypt produced a gluycoamylase which when purified had a molecular weight of 51,300 +/- 800 Daltons. The optimum pH for activity was 4 and the optimum temperature was 60 degrees C. The enzyme was stable at 70 degrees C for 15 min but denatured at 90 degrees C over 30 min. The Km value with soluble starch was 2.85 mg ml-1, and 10 mM HgCl2 inhibited the enzyme. It was possible to store the enzyme for at least 1 year at -20 degrees C without significant loss in activity.

Aspergillus flavus↗

Colon carcinoma cells switch their response to transforming growth factor beta 1 with tumor progression.

Transforming growth factor beta 1 (TGF-beta 1) switches from an inhibitor of tumor cell growth to a stimulator of growth and invasion during human colon carcinoma progression. We originally observed that metastatic colon carcinoma cells in primary culture responded to TGF-beta 1 by proliferation, whereas moderate to well-differentiated primary site colon carcinomas were growth inhibited by TGF-beta 1 (P. Schroy et al., Cancer Res., 50: 261-265, 1990). We then cloned several colon carcinoma cell lines which modeled these responses to TGF-beta 1 and expressed TGF-beta 1 (M. M. Hafez et al., Cell Growth & Differ., 1: 617-626, 1990; 3: 753-762, 1992). Two of these colon carcinoma cell lines, U9 and HD3, which activate approximately equal amounts of TGF-beta 1 and express equal amounts of TGF-beta receptors, are now used to compare the effects of TGF-beta 1 in modulating invasive behavior. The U9 cell line exhibits autocrine-positive growth regulation in vitro by TGF-beta 1, whereas the HD3 cell line shows the opposite response, autocrine-negative regulation. Blocking endogenous TGF-beta 1 with isotype-specific antibody inhibited U9 cell growth because autocrine TGF-beta 1 acts as a mitogen for U9 cells. In contrast, antibody to TGF-beta 1 stimulated HD3 cell proliferation because autocrine TGF-beta 1 inhibits growth of these cells. U9 cells were 13-fold more invasive in vitro through a collagen I layer than HD3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The meiotic stage of nondisjunction in trisomy 21: determination by using DNA polymorphisms.

We have studied DNA polymorphisms at loci in the pericentromeric region on the long arm of chromosome 21 in 200 families with trisomy 21, in order to determine the meiotic origin of nondisjunction. Maintenance of heterozygosity for parental markers in the individual with trisomy 21 was interpreted as resulting from a meiosis I error, while reduction to homozygosity was attributed to a meiosis II error. Nondisjunction was paternal in 9 cases and was maternal in 188 cases, as reported earlier. Among the 188 maternal cases, nondisjunction occurred in meiosis I in 128 cases and in meiosis II in 38 cases; in 22 cases the DNA markers used were uninformative. Therefore meiosis I was responsible for 77.1% and meiosis II for 22.9% of maternal nondisjunction. Among the 9 paternal nondisjunction cases the error occurred in meiosis I in 2 cases (22.2%) and in meiosis II in 7 (77.8%) cases. Since there was no significant difference in the distribution of maternal ages between maternal I error versus maternal II error, it is unlikely that an error at a particular of maternal ages between maternal I error versus maternal II error, it is unlikely that an error at a particular meiotic stage contributes significantly to the increasing incidence of Down syndrome with advancing maternal age. Although the DNA polymorphisms used were at loci which map close to the centromere, it is likely that rare errors in meiotic-origin assignments may have occurred because of a small number of crossovers between the markers and the centromere.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Susceptibility to and severity of rheumatoid arthritis in multicase families.

Fifteen sibships, each having two or more siblings affected by classical or definite RA were studied. They comprised 31 patients with RA (all in remission) and 21 normal siblings. The total severity index of RA was assessed by clinical and radiological indices. For all the patients the following investigations were carried out: (1) HLA antigens determination for nine antigens at A locus and 15 at B locus and 6 at DR locus; (2) rheumatoid factor. We found: (1) RA disease is genetically controlled and the responsible genes are linked to the HLA system; (2) association between seropositivity and DR4 and DR4/B27 genotypes; (3) significant effect of the genotype DR4/B27 on the age of onset; (4) association between the increase in disease severity both clinical and radiological and DR4/X and DR4/B27 phenotypes. Thus the genetic control is probably composed of two types of genes: disease susceptibility genes and disease severity genes linked to DR4/X and DR4/B27 phenotypes.

Adolescent↗

A new beta-thalassaemia frameshift mutation detected by PCR after selective hybridization to immobilized oligonucleotides.

A previously undescribed mutation (-1, +3, codon 24) causing beta-thalassaemia was identified in an Egyptian patient. It consists in the concomitant deletion of a G in codon 24 and its replacement with the new trinucleotide CAC, thus resulting in the shift of the beta-globin reading frame. The sequence of the chromosome of interest was isolated from the homologous one by means of selective hybridization to an immobilized oligonucleotide. The presence of this mutation in the proband's family was confirmed by dot blot hybridization with an oligonucleotide probe.

Base Sequence↗

Immunogenetic susceptibility for post-schistosomal hepatic fibrosis.

In 19 children with hepatic fibrosis as the result of continued schistosomiasis mansoni and 20 children without hepatic fibrosis, the following studies were carried out: HLA antigen typing for 30 antigens, immune response of T lymphocytes to schistosome antigen by measuring DNA synthesis evidenced by 3H-thymidine uptake, and measurement of total OKT3+, OKT4+, and OKT8+ cells using monoclonal antibodies. Patients with hepatic fibrosis were mostly high responders in contrast with those without fibrosis. High immune response and susceptibility to post-schistosomal hepatic fibrosis were associated with a high frequency of A2 and B12 antigens and a lack of DR2 antigens, while low response was associated with the presence of the DR2 antigen. The T4+:T8+ ratio showed increased suppressor proportions in patients with low immune response and/or with no hepatic fibrosis. We suggest an immunogenetic susceptibility for post-schistosomal hepatic fibrosis, probably controlled by HLA-linked genes via the suppressor T cells.

Adolescent↗

Molecular characterization of beta-thalassemia mutations in Egypt.

The relative frequency of different beta-thalassemia mutations and their association with beta-globin haplotypes were studied in patients from the Nile delta region, Egypt, by means of the polymerase chain reaction, oligonucleotide hybridization and restriction analysis. We found that 8 mutations account for 77% of beta-thalassemia chromosomes in this population, the commonest being IVS-1 nt 110, IVS-1 nt 6 and IVS-1 nt 1. Each mutation was associated with a specific haplotype, with the exception of IVS-1 nt 110, found on 3 different chromosomal backgrounds. Our data show that testing for the 8 detectable mutations makes feasible prenatal diagnosis in 65% of at risk couples and exclusion testing in an additional 25% of cases.

Egypt↗

Immunogenetic study of the response to streptococcal carbohydrate antigen of the cell wall in rheumatic fever.

An immunogenetic study of the response to streptococcal carbohydrate antigen of the cell wall was carried out on members of 15 multiplex families each having more than one sib affected with rheumatic heart disease. They comprised 30 parents and 61 sibs (32 with rheumatic disease and 29 without). Fifty healthy unrelated subjects served as controls. A history was taken and clinical examination carried out. Rheumatic activity was determined and HLA typing was carried out for nine A antigens, 15 B antigens, and six DR antigens. The immune response of lymphocytes to streptococcal polysaccharide antigen of the cell wall of group A beta haemolytic streptococci in vitro was studied by tritiated thymidine uptake. The results were statistically and genetically analysed. It was found that (a) all subjects with rheumatic disease were highly responsive to the streptococcal polysaccharide antigen of the cell wall, the sib pairs being mostly HLA identical; (b) all low responders had no rheumatic disease and their phenotypes were mostly different from those of the rheumatic member of their sib pair; (c) correlation of immune responsiveness (high or low) between HLA-identical sibs was significant, but insignificant between haplotype identical and non-identical sibs; (d) the gene responsible for high responsiveness to the streptococcal polysaccharide antigen of the cell wall is recessive and closely linked to HLA. In conclusion, it was found that exposure to pharyngeal infection with group A beta haemolytic streptococci may lead to acute rheumatic fever in those with an inherited recessive gene responsible for high responsiveness to the streptococcal polysaccharide antigen of the cell wall.

Adolescent↗

A new beta-thalassemia mutation produced by a single nucleotide substitution in the conserved dinucleotide sequence of the IVS-I consensus acceptor site (AG----AA).

An Egyptian child with thalassemia major was found to carry two different haplotypes (I and VI) associated with two beta-thalassemic chromosomes. Analysis with several oligonucleotides and restriction enzymes, which identify the mutations most common in the Mediterranean area, allowed the identification of only one mutation, namely T----C at position 6 of the first intervening sequence (IVS-I). In order to characterize the other mutation the beta gene was amplified with polymerase chain reaction and sequenced. A G----A substitution was found at position 130 of the IVS-I which alters the conserved dinucleotide AG present in the consensus acceptor sequence, thus producing a beta (0)-thalassemia. This mutation was further confirmed by restriction analysis since it creates a new restriction site for the enzyme Afl II. It is concluded that this subject carries the IVS-I-6 mutation associated with haplotype VI, frequently observed in Mediterranean areas, and a new mutation at the acceptor site of the IVS-I, which has not been described before, associated with haplotype I. This thalassemic gene can be added to the list of mutations that can be identified by Southern analysis using Afl II.

Amino Acid Sequence↗

Spinal dysraphism: experience with 250 cases operated upon.

During a period of 4 years (December 1983-December 1987) 250 children were operated upon by the authors. At the outpatient clinic of the New Children's Hospital 313 infants and children suffering a myelodysraphic lesion were seen, 63 of whom were not treated surgically owing to the presence of severe hydrocephalus in 16 cases and complete flaccid paraplegia with marked sphincteric disturbances in 47. All of the patients came from poor families. Malnutrition, many siblings per family, poor maternal care, and repeated pregnancies and abortions have added to the large incidence of such a handicap in Egypt. The clinical features, diagnosis, and management of 200 cases of spinal bifida aperta (SBA) and 50 of spina bifida occulta (SBO) are summarized. SBA cases were operated upon as soon as possible from the time of their presentation; their preliminary assessment included an exhaustive general, neurological, urological, and orthopedic examination; and investigations such as plain X-rays to the back and skull, CT scanning of the cranium, spinal myelogram, and metrizamide CT scanning to the back were performed. The surgical outcome is far from being satisfactory in the sense of producing an ambulatory, intelligent, healthy individual, especially in a meningomyelocele patient having a high-level lesion. The authors believe that there is still much to be done for these children marked by fate, and the neurosurgeon should be one among several other physicians devoted to the amelioration or at least the prevention of worsening, if possible, of the condition in such unfortunate and handicapped children.

Child↗

Frequency and molecular types of deletional alpha-thalassemia in Egypt.

The frequency of deletional alpha-thalassemia in the Egyptian population was estimated at 0.08 by DNA analysis of a newborn random sample. No alpha 0 determinants were found. The most frequent alpha+ determinant was the -alpha 3.7 type I in association with the medium allele at inter-zeta HVR. The -alpha 4.2 and alpha alpha alpha anti 3.7 arrangements were found at very low frequencies.

Chromosome Deletion↗

Evidence of inherited susceptibility of increased streptococcal adherence to pharyngeal cells of children with rheumatic fever.

The study included the members of 15 families, each having more than one sibling affected by rheumatic fever (RF). All the rheumatic individuals showed the sequelae of rheumatic carditis, but on clinical and laboratory evidence, the disease was inactive. Thirty normal unrelated individuals, having no rheumatic first-degree relatives, were studied as controls. The following investigations were carried out for all members: (1) history and clinical examination, (2) routine investigations of diagnosis, (3) HLA typing using 9-A, 15-B, 6-DR antigens, (4) adherence of group A streptococci to pharyngeal cells, an in vitro adherence assay. There were two types of strains; five RF-associated strains and two RF-unassociated strains. Statistical and genetic analysis revealed: (1) no significant difference between adherence of RF-associated and unassociated strains amongst controls; (2) significant increased avidity for adherence of RF-associated strains amongst rheumatic siblings compared to normal siblings and controls. There was no significant difference between the three groups using RF-unassociated strains; (3) HLA-haplotype concordance and 'N' measure showed that the avidity for adherence is probably inherited; (4) lod scores for linkage suggest a dominant susceptibility gene(s) closely linked to HLA and segregating in multiplex families.

Bacterial Adhesion↗

Studies of peripheral blood T lymphocytes in assessment of disease activity in rheumatic fever.

The study included three groups of children: (a) 38 with active rheumatic fever (ARF) and active carditis; 21 seen during their first attack and 17 during recurrence of activity, (b) 47 with inactive rheumatic fever (IARF); the period since activity was less than 3 years in 31 cases and more than 3 years in 16 cases. Using monoclonal antibodies and T lymphocyte blast transformation induced by PHA, we found: (1) low total T lymphocytes, helper-inducer cells and helper-inducer/suppressor-cytotoxic ratio which persisted for years; and (2) reduced lymphoblast transformation in active disease.

Adolescent↗