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Biomedical subjects

M Hafez

Publications and source records attributed to M Hafez.

At least 37 records · Page 2Linked to original sources

Immune regulation dysfunction in chronic persistent hepatitis.

The study included 19 children diagnosed clinically, biochemically, and by liver biopsy as having chronic persistent hepatitis. The following investigations were carried out: 1. detection of total T-lymphocytes, T-helper, and T-suppressor cells using monoclonal antibodies (OKT3, OKT4 and OKT8); 2. determination of HLA-A, B and DR antigens using the microcytotoxicity technique. The results were analysed in comparison with data from a normal control group. There are several important findings. First, low total T-lymphocytes with increased proportion of suppressor cells (P less than 0.001). Second, strong association between HLA-A1 antigen and CPH (Fisher exact = 0.000022). Third, significant association between the immunoregulatory dysfunction and A1 antigen (Fisher exact = 0.033). This observation suggests that a genetic component may influence susceptibility to CPH through an increased suppressor response.

Adolescent↗

Inherited immunoregulatory dysfunction in extrinsic bronchial asthma.

We studied 119 members of 22 asthmatic multiplex families. Included were: 44 parents (seven were asthmatics), 48 asthmatics (23 were undergoing an attack at the time of sampling), and 27 normal siblings. The following investigations were carried out on all subjects: 1) detection of total T lymphocytes, helper cells, and suppressor cells, using monoclonal antibodies (OKT3, OKT4, and OKT8), 2) study of nonspecific T-lymphocyte blast transformation induced by PHA, and 3) HLA-A, B, and DR antigen determination using the microcytotoxicity technique. The results were compared with normal ranges and data for a normal group and statistically and genetically analyzed. They indicate that: 1) the number of T cells was low in asymptomatic asthmatics and normal in asthmatics in attack; 2) there were fewer helper and normal suppressor cells (that is, a low H:S ratio) in asymptomatic asthmatics, and a normal amount of helper and suppressor cells (a normal H:S ratio) in those experiencing an attack; 3) there was a percentage of lymphocyte transformation in both groups of asthmatics; 4) whereas the T-helper cells increased, there was no change in the number of suppressor cells during an attack, which points to deficient function of suppressor cells; 5) the disorder is inherited and the gene controlling this dysfunction is HLA-linked and probably dominant.

Adolescent↗

Presumptive evidence for an immunosuppressor susceptibility gene, linked to HLA, in rheumatic fever.

In a study of rheumatic carditis, 135 members of 21 multiplex families have been investigated, along with 60 normal unrelated control individuals. Circulating T-lymphocytes were reduced (as a percentage of total blood mononuclear cells) in all 'rheumatic' individuals, in 7 of 40 normal parents, and in 8 of 49 normal sibs. An immune response characterized by an increase in the proportion of suppressor T cells occurs in most individuals affected by rheumatic carditis and this change persists for a long time. Genetic analysis revealed three important points: 1. increased HLA haplotype sharing amongst the affected sib-pairs; 2. the possibility of using low circulating T-cell percentage as a marker of susceptibility; 3. presumptive evidence for a recessive susceptibility gene linked to HLA and responsible for the suppressor cell response.

Female↗

Immunogenetic aspects of febrile convulsions.

Thirty-nine mentally normal unrelated children diagnosed as having febrile convulsions were included in this study. The following have been carried out: (a) detailed anamnesis and clinical examination; (b) cerebrospinal fluid investigation; (c) EEG examination between attacks; (d) HLA-antigen determination; (e) estimation of serum IgA, IgG, IgM; and (f) counting of percent spontaneous E-rosette formation. The results were statistically compared to normal Egyptian controls. The results could be summarised as follows. (1) Only HLA-B5 antigen frequency is high among patients (chi 2c = 19.1, P less than 0.0001). Relative risk is 4.4 which shows significant association (WY2 = 29.145, P less than 0.0001) and etiologic fraction equals 0.377. (2) The means of IgA and E-rosette in the patients were significantly low (t = 3.46, P less than 0.01 and t = 3.92, P less than 0.001, respectively), (3) HLA-B5 is the only antigen with high frequency among the two groups of patients with low IgA and E-rosette (chi 2c = 11.9 and 18.2, respectively). (4) There is a significant association between B5 and low IgA (P less than 0.05) but not with low E-rosette (P greater than 0.05). The suggestion is that the genetic control of febrile convulsions is in linkage disequilibrium with HLA-B5, low IgA and low total T-cells. This altered immune function in otherwise normal children with febrile convulsions may predispose them to acute infections and high fever which precipitate convulsions.

Child↗

Increased frequency of induced sister chromatid exchanges in kwashiorkor.

The study included 16 infants with advanced manifestations of kwashiorkor and 16 unrelated age-matched normals as controls. Whole blood samples, at room temperature, were exposed to gamma-rays in increasing dosages. Lymphocytes were cultured; phytohaemagglutinin and bromodeoxyuridine (10 microM) were added, at initiation of culture, and harvesting was performed after 64 to 68 h. Slides were coded and sister chromatid exchanges (SCE) counted. In controls, no significant increase in the frequency of SCE was found. For kwashiorkor infants the SCE frequencies showed significant increase as irradiation dosages rose. It is concluded that the changes observed are probably due to alteration in: the cell cycle length; activities of enzymes responsible for DNA repair; DNA growing points; and protection of cells from chromosome breakage.

Child, Preschool↗

HLA-antigens in the Egyptian population.

HLA-A, -B and -DR markers were determined for 380 normal unrelated Egyptians of both sexes. Typing for 9 A-locus, 15 B-locus and 6 DR-locus alleles was done. Antigen, gene and haplotype frequencies and delta-values were estimated. The data obtained were statistically compared to those of Arabs at Gaza Strip, European and American Caucasians, American Blacks, African Blacks and Japanese (Orientals). The Egyptian genetic make-up was found to be heterogenous and some HLA markers differ significantly from that of other ethnic groups as well as Arabs from the Gaza Strip.

Adolescent↗

Enhanced response to the induction of sister chromatid exchange by gamma radiation in neurofibromatosis.

The study included 8 unrelated patients with neurofibromatosis, and 10 unrelated normal and healthy persons as controls. Whole blood samples were divided into plastic T flasks and exposed at room temperature to gamma rays. The radiation dose was 36 rad/minute, and the doses delivered were 0, 75, 150 and 300 rad. The lymphocytes were cultured in (RPMI) 1640 tissue culture medium and autologous serum (20%). Phytohemagglutinin and bromodeoxyuridine (Brdu) (10 microM) were added at initiation of culture and harvesting was done 64 to 68 hours after culture initiation. Slides were coded, differential staining was done, and sister chromatid exchanges (SCEs) and aberrations (gaps, breaks, dicentrics, fragments and minutes) were counted. In the controls no significant increase in frequency of SCE has been found (P greater than 0.5). In the patients, the frequencies significantly increased with the increase of dose of irradiation (P less than 0.001). Furthermore, after irradiation, the incidence of gaps, breaks, and dicentrics were significantly increased in patients compared with controls. Moreover, the incidence increased with the increase in the dose of radiation. The results are discussed with a conclusion that the results add to the indication of a genetic predisposition to develop cancer in neurofibromatosis patients.

Adolescent↗

Improved erythrocyte survival with combined vitamin E and selenium therapy in children with glucose-6-phosphate dehydrogenase deficiency and mild chronic hemolysis.

To study the antioxidant effect of high-dose vitamin E alone and in combination with selenium in patients with glucose-6-phosphate dehydrogenase deficiency with mild chronic hemolysis, 36 male children with such manifestations were enrolled consecutively into two equal groups. Group 1 received 800 IU vitamin E daily, and group 2 received 800 IU vitamin E in combination with 25 micrograms selenium. Hematologic status before and 2 months after treatment was evaluated. After treatment there was a significant change toward normal in both groups. The mean red cell half-life increased in group 1 from 16.9 to 22.8 days (P less than 0.01), and in group 2 from 15.6 to 24.3 days (P less than 0.01). A comparison of the mean difference of paired values in the two groups revealed a more significant increase in hemoglobin (0.9 +/- 0.1 gm/dl vs 1.2 +/- 0.2 gm/dl, P less than 0.05), hematocrit (2.4% +/- 0.4% vs 3.8% +/- 0.3%, P less than 0.05), and red cell half-life (5.9 +/- 3.0 days vs 9.1 +/- 4.4 days, P less than 0.01), and more significant reduction in reticulocytes (-0.7% +/- 0.2% vs -1.5% +/- 0.4%, P less than 0.01) in group 2. Clinical assessment and follow-up indicated no side effects related to the drugs.

Adolescent↗

HLA antigens in multiplex families with isolated congenital heart disease.

Twelve multiplex families with isolated congenital heart diseases (CHD) were included in the study. In 9 families the types of CHD in the living sibs were concordant and in the other 3 were discordant. All families were subjected to the following: (1) Pedigree construction, (2) clinical examination of the parents, affected and unaffected sibs, (3) investigations of patients, to establish the diagnosis, (4) chromosomal analysis for the patients, (5) HLA antigen typing for the parents, affected and unaffected sibs for 9 antigens at the A locus, 15 at B and 6 at the DR locus. The results can be summarized as: (a) sibs with two different types of CHD showed identical haplotypes; (b) the segregation of haplotypes among disease sibpairs is inconsistent with Mendelian segregation; (c) increased frequency of concordant HLA haplotypes among diseased siblings; (d) Morton's exact test revealed that the data best fit a hypothesis of a recessive susceptibility gene, linked to HLA.

Disease Susceptibility↗

Evidence of chromosomal instability in neurofibromatosis.

Blood lymphocytes from six unrelated patients with neurofibromatosis and three normal controls were examined for their response to different doses (0, 75, 150, 300, 400 rad) of x-radiation, as measured by chromosome aberrations (gaps, breaks, dicentrics, centric rings, acentric ring, fragments, and minutes). Cytogenetic studies on phytohemagglutinin-stimulated cells revealed chromosomal instability in the neurofibromatosis lymphocytes as shown by the significant increase in the in the incidence of gaps, breaks and dicentrics. This increase paralleled the increase in the dose of irradiation. The significance of these findings is discussed.

Adolescent↗

HLA antigens and acute rheumatic fever: evidence for a recessive susceptibility gene linked to HLA.

From 60 probands with acute rheumatic fever (ARF), 19 multiplex families segregating for ARF were ascertained. The parents and rheumatic and normal sibs of the probands in these 19 families were also studied. HLA typing using the microlymphocytotoxic assay was then performed on the 60 unrelated probands, the multiplex families, and 234 unrelated controls using 23 antigens from the HLA-A and -B loci. The controls lacked a past history of ARF and were from the same geographic locality. Calculations of relative risk demonstrate an increase of HLA-B5 antigen in the 60 patients, but the result might not be significant from the point of view of multiple comparisons. Nevertheless, affected sib pairs from the multiplex families show 93% concordance for both or one HLA haplotype. A formal linkage analysis demonstrates that a recessive etiology is most likely (lod score of 3.3) with approximately 68% of cases being due to a gene closely linked to HLA and in linkage disequilibrium with HLA-B5. The remaining 32% of cases are due to other familial factors such as polygenic inheritance or common environmental factors. The results confirm a strong genetic predisposition to ARF and its heterogeneous nature in families.

Gene Frequency↗

HLA-antigens and tuberculosis in the Egyptian population.

Peripheral blood lymphocytes from 42 unrelated Egyptian patients with tuberculosis and 156 healthy persons were HLA phenotyped for the A,B and DR loci using the NIH lymphocytotoxicity tests. Statistical analysis of the results showed that A2 and B5 had significantly increased frequencies among patients with tuberculosis compared with the controls. Patients with A2 had more severe disease than did patients without A2 and the number with B5 antigen was less than those without the antigen. This observation suggests that A2 and B5 may influence susceptibility to tuberculosis, but not the course of the disease. Furthermore, a linkage disequilibrium was found between A2 and B5 antigen among tuberculous patients, but their association bore no relation to the severity of the disease.

Adolescent↗

Chromosomal analysis of neuroblastoma.

Ten children with abdominal neuroblastoma were included in the study. Biopsies from the neuroblastomas were taken during surgical operations, nine from the primary tumours and one from a metastasis. Histopathology was done for diagnosis. Chromosomal cultures of neuroblastoma cells and peripheral blood lymphocytes were performed. The peripheral blood lymphocytes revealed normal chromosomal complements. The 10 tumours were in the peridiploid range with random gains or losses of chromosomes. Deletion of the short arm of chromosome number 1 distal to band p31 occurred in 6 tumours. Other structural changes and giant markers were found. It was concluded that a regulatory gene controlling the transformation gene of neuroblastoma, is present at or distal to lp31.

Abdominal Neoplasms↗

Genetic susceptibility in pityriasis versicolor.

300 patients with pityriasis versicolor, 168 males and 132 females, of different ages were included in this study. Each was subjected to a detailed structured questionnaire. All the available relatives had been examined. Pedigrees were constructed and segregation analysis was done using the mathematics of population genetics. The collected data showed genetic susceptibility which is inconsistent with any of the single gene defects but fulfill the criteria of multifactorial (genetic-environmental) inheritance. The heritability was estimated to be 22.2% in the first-degree relatives.

Chromosome Aberrations↗

HLA-antigens in Guillain-Barré syndrome.

A microlymphocytotoxicity test determined serologically the frequency of HLA antigens in 32 patients with Guillain-Barré syndrome and in 234 healthy control subjects. The results demonstrated significantly increased frequencies of A3 and B8. The relative risk was estimated to be 9.6 and 4.6 for the A3 and B8 antigens, respectively. Study of the gametic association revealed weak positive linkage disequilibrium and biological association. The results are discussed, and it is concluded that the aberrant genetic make-up of the patients makes them more susceptible to develop the syndrome after exposure to the environmental factor(s).

Child↗