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Biomedical subjects

M A Ibrahim

Publications and source records attributed to M A Ibrahim.

At least 19 recordsLinked to original sources

Sensitization of allo-specific T lymphocytes in vivo: role of antigen-presenting cells.

The migratory behavior of antigen-presenting cells was investigated in vivo. Purified murine splenic dendritic cells and splenic and peritoneal macrophages were labelled and injected subcutaneously in the hind foot-pads of mice and monitored for seven days. In the first 24 h, a small quantity of label was recovered from popliteal but not inguinal lymph nodes with radioactive (111In-oxine and 3H-uridine) but not fluorescent (1,1'-dioctadecyl 3,3,3'3'-tetramethylindocarbocyanine perchlorate and fluorescein isothiocyanate) labelling of the antigen-presenting cells. Chemical fixation of the injected antigen-presenting cells had no effect on the detection of label in the popliteal lymph nodes, suggesting that it was unlikely to be due to active cellular migration. Label recovery from hind feet declined with time over the seven day period and was independent of the label type. Essentially the same observations were made whether the antigen-presenting cells were syngeneic or allogeneic to the injected mice and irrespective of the type of antigen-presenting cell used. However, allogeneic antigen-presenting cells, which did not migrate to the draining lymph nodes, successfully primed T lymphocytes in these lymph nodes as shown by a secondary in vitro mixed leukocyte reaction. Again, chemical fixation of the injected antigen-presenting cells had no effect on their ability to prime allogeneic T lymphocytes in the draining lymph nodes. These experiments suggest that, during experimental allo-sensitization via the subcutaneous route, indirect priming of allogeneic T lymphocytes may be a dominant pathway.

Animals

Renal allograft-infiltrating lymphocytes. A prospective analysis of in vitro growth characteristics and clinical relevance.

One-hundred consecutive human renal allograft Tru-cut needle biopsies were studied for in vitro proliferation of T lymphocytes under restrictive culture conditions containing low-dose recombinant interleukin 2. Each biopsy was entered into a blinded code and evaluated prospectively for visual evidence of growth at 24 hr and for sustained growth. Those T cell populations exhibiting sustained growth were then evaluated for cell surface phenotype by FACS; for allospecific cytotoxicity by 51Cr release; for a proliferative response to alloantigen by incorporation of [3H]-thymidine; and for secretion of IL-2, IL-4, IFN-gamma, and TNF-alpha in response to alloantigenic stimulation by ELISA. All results were compared with clinical diagnosis, immunosuppression at time of biopsy, diagnosis and phenotype by immunopathology, short-term outcome and long-term graft survival. Growth at 24 hr was predictive of acute cellular rejection (P less than 0.0005), unrelated to chronic rejection (P = 0.663) or maintenance immunosuppression (P = 0.911), and inversely correlated with cyclosporine toxicity (P = 0.051) and treatment with OKT3 (P = 0.014). The CD4/CD8 ratio of the sustained T cell populations was unrelated to that seen on histological examination (correlation coefficient = -0.098 and 0.044 for diffuse and aggregate infiltrates, respectively). Cytotoxic specificity for HLA class II was mediated by CD4+ cells and for HLA class I by CD8+ cells. Enhanced secretion of IL-2 in response to alloantigen distinguished those cells associated with irreversible allograft damage from those associated with complete functional recovery (P = 0.01). This study demonstrates that early evaluation of T cell proliferation in vitro identifies activated T cell infiltrates mediating acute cellular allograft rejection in a time frame suitable for clinical diagnostic application. It strengthens the concept that donor-specific cytotoxicity is governed by the stabilization of the alloantigen-T-cell receptor interaction by the accessory molecules CD4 and CD8, but either interaction is equally able to participate in an episode of acute rejection. Irreversible graft injury is associated with infiltrating cells that are capable of amplifying their responsiveness through secretion of IL-2.

CD4 Antigens

A study of the morbidity pattern of referred patients and the effectiveness of the referral system in primary health care centers.

Patient referral system is considered to be an important element in achieving the objectives of the Primary Health Care services. Patients attending the Primary Health Care Center (PHCC) expect basic medical care and appropriate follow-up services. Thus, patients requiring further evaluation and treatment are referred to a secondary health care facility. In this study the morbidity pattern as well as the referral system was evaluated in selected PHCC in the city of Jeddah. A systematic random sample of all the patient referrals from selected PHCC's were analyzed. A total of 1,164 referrals were studied, 59.9 per cent were females and 40.1 per cent were males. The contents of referral letters from PHCC to hospitals as well as feed back from hospitals were analyzed. The majority of referrals were for the age group 25-44 years old 458 (39.3%). The results demonstrated that 5 per cent of patients were routinely referred to the secondary health care centers, and the feedback from these secondary health care facilities was (22.7%). It was also noted that the majority of referral letters lack commonly accepted standards of information about the patient. It was concluded that the follow-up and feed-back system needs to be reinforced. The primary health care providers need to review the patient referral system and implement specific criteria for the optimum utilization of this essential service for the benefit of the community.

Adolescent

Characterisation of ribosomes from drug resistant strains of Schizosaccharomyces pombe in a poly U directed cell free protein synthesising system.

Mutants of Schizosaccharomyces pombe were isolated as resistant either to trichodermin or to anisomycin. Growth tests showed that the majority of mutants isolated were cross resistant to both drugs and also to cycloheximide. A limited genetic analysis showed that mutants at least four loci, tri3, tri4, ani1 and ani2, had this phenotype as was also the case for mutants at three cycloheximide resistant loci, cyh2, cyh3 and cyh4 reported previously (Ibrahim and Coddington, 1976). Allelism tests showed that the tri3, ani2 and cyh4 strains were allelic. A mutant at another trichodermin resistant locus, tri5, was cross resistant to anisomycin but sensitive to cycloheximide. Ribosomes from wild type and selected strains were analysed in a poly U directed cell free protein synthesising system. Three strains, cyh1-C7, ani1-F1 and tri-N15 (probably a tri5 allele) possessed ribosomes which were more resistant than the wild type to the drugs used in their isolation. In each case the site of the resistance was in the 60S subunit. Ribosomes from the cyh2, cyh3 and cyh4 strains were as sensitive to cycloheximide as those from wild type.

Anisomycin

Physician opnions on the use of antibiotics in respiratory infections.

To investigate the feasibility of establishing standards of care based on a broad consensus, a questionnaire concerning the management of signs and symptoms of common respiratory infections in infants was given to a national sample of pediatric infectious disease specialists, general pediatricians, and family physicians. There was significant disagreement (p less than .01) among the three groups of physicians in 15 of the 18 clinical situations concerning the appropriateness of prescribing antibiotics. Whenever there was disagreement, the family physician group was most inclined and the infectious disease group least inclined to favor antibiotics therapy. More than 75% of each group favored antibiotics in the same situation in only three instances. These results suggest that it may be difficult to set widely accepted standards for the evaluation of medical care where there are such differences of opinion.

Age Factors

Genetical studies on revertants to sensitivity from a cycloheximide resistant strain of Schizosaccharomyces pombe.

Six UV induced cycloheximide-sensitive revertants were isolated from the cyh1-C7 strain of Schizosaccharomyces pombe which is resistant to cycloheximide. In all cases reversion to sensitivity was due to a forward mutation in a second suppressor gene. Genetical analysis showed that at least two genes, designated scr1 and scr2 (scr=suppression of cycloheximide resistance) were involved. Both scr1 and scr2 suppressed the resistance of six independently isolated alleles at the cyh1 locus. They had no effect on two known nonsense mutations in the ade7 locus. The cyh1-C7 strain has an altered 60S ribosomal protein which can be detected by two-dimensional polyacrylamide gel electrophoresis. In two suppressed strains, cyh1-C7 scr1 and cyh1-C7 scr2, the original altered protein was present. However no further ribosomal protein differences were observed which could be correlated with the presence of the scr genes. Both scr mutations conferred cold sensitivity on the organism indicating that they were of the missense type. Hence it seems certain that scr1 and scr2 are not mutations in tRNA genes leading to either nonsense or missense suppression. There is however no direct evidence that they code for ribosomal proteins and exert their effect on cyh1-C7 at the ribosomal level.

Cycloheximide

A method for selecting criteria to evaluate medical care.

This study tests a questionnaire method for eliciting process criteria for medical care appraisal. The questionnaire was sent to national samples of family physicians, pediatricians, and pediatricians specializing in infectious diseases asking their opinions about various clinical actions in 125 clinical situations concerning respiratory infection in infants. Five hundred twenty-four (54%) physicians returned completed questionnaires. Questionnaire responses favored the performance of a majority of actions and opposed very few. Opinions concerning individual actions, particularly diagnostic tests and treatments, varied widely depending upon the clinical situation presented. A second questionnaire sent one year later indicated that the opinions expressed in the first questionnaire remained stable over time, especially if the initial opinion favored performance of the action. Comparison of the questionnaire responses and medical records of a group of practitioners demonstrated that only 55% of actions favored in a practitioner's questionnaire appeared in his records. Although the questionnaire method appears to be a feasible, specific, and reliable means of identifying clinical opinion, there remains considerable discordance between opinion as expressed in the questionnaire and recorded clinical practice.

Humans

Influence of training and experience on selecting criteria to evaluate medical care.

To determine whether training and experience affect the selection of process criteria for evaluating medical care, three groups of physicians (family physicians, general pediatricians, and pediatricians specializing in infectious disease) were sent a questionnaire asking their opinions about various clinical actions in 125 clinical situations concerning respiratory infections in infants. Five hundred and twenty-four (54 per cent) physicians returned completed questionnaires. The three groups agreed in 93 (74 per cent) situations, especially about history taking, physical examination, and follow-up observation. Disagreements occurred most often regarding antibiotic use. Of the three groups, the family physicians selected the most extensive list of recommended actions including the greatest number of indications for antibiotics. The general pediatricians selected the fewest situations requiring history taking, physical examination and diagnostic tests. The infectious-disease pediatricians felt the greatest necessity to record history and physical-examination items but were the most restrictive in recommending antibiotics and other drugs.

Anti-Bacterial Agents

Genetic studies on cycloheximide-resistant strains of Schizosaccharomyces pombe.

Cycloheximide-resistant mutants of Schizosaccharomyces pombe were isolated either as spontaneous mutants or after mutagenic treatment with nitrous acid, UV and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Twenty-three spontaneous mutants and 64 induced mutants were analysed genetically. Crosses revealed that at least four loci, designated cyh1, cyh2, cyh3 and cyh4 are responsible for resistance. Alleles of cyh1 show good growth on either high (100 mug/ml) or low (40 mug/ml) concentrations of cycloheximide whereas alleles at the cyh2, cyh3 and cyh4 loci gorw well on 40 mug/ml but poorly on 100 mug/ml. Some alleles at the cyh2 and cyh3 loci are also temperature sensitive (ts), the ts phenotype being conferred by the same gene as the resistance. In diploids, cyh1 and cyh4 are re-essive to wild type whereas cyh2 and cyh3 are semi-dominant. There was no intragenic complementation between three cyh1 alleles. Cross-resistance to trichodermin and anisomycin was shown by cyh2, cyh3 and cyh4 but not cyh1. Most cyh1 alleles, of spontaneous and UV origin only, were cold sensitive (cs) at 14 degrees and some of these were also cycloheximide dependent at the same temperature. It is suggested that the cyh1 and cyh4 genes are involved in ribosome formation or function and the other loci probably affect the uptake of cycloheximide by the cells.

Anisomycin

Epidemiology of organomercury poisoning in Iraq. II. Relationship of mercury levels in blood and hair to exposure and to clinical findings.

In the survey described by Al-Mufti et al. (see page 23) blood and hair samples were analysed for total mercury by modified atomic absorption spectrophotometry. The hair samples were divided into 2.5-cm segments and analysed consecutively. The mean blood levels were 34 ng/ml and 7 ng/ml, respectively in those who had and those who had not eaten contaminated bread.Corresponding mean maximum hair mercury values were 136 mug/g and 5 mug/g, respectively. Hair mercury values provided a better discrimination between different categories of exposure than blood mercury values at the time the survey was performed, some months after the end of the outbreak. Those persons who had not eaten contaminated bread but who lived in the area of high exposure had hair mercury values between the values of those who had eaten and those who had not eaten contaminated bread and who lived in the area of low exposure. Sequential estimation of mercury in 2.5-cm segments of hair in women gave information on the period of accumulation of mercury more than 1 year before the time of collection of the samples. It was possible to show an approximate relationship between the maximum hair mercury value and the amount of contaminated bread eaten. The match between the blood mercury level and the severity of poisoning was poor, owing to the length of time that had elapsed between the onset of poisoning and the sampling. With hair mercury, while the group results showed a good relation to the severity of poisoning, in individual cases the match was less good, especially in those persons where an insufficient length of hair was available for analysis. Biological variation in sensitivity to methylmercury was also likely to have been an important factor.

Adolescent