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Biomedical subjects

M A Ibrahim

Publications and source records attributed to M A Ibrahim.

At least 37 records · Page 2Linked to original sources

Enhancement of intervertebral disks with gadolinium complexes: comparison of an ionic and a nonionic medium in an animal model.

PURPOSE: To compare MR contrast enhancement of intervertebral disk tissue after intravenous administration of equimolar doses of an ionic and of a nonionic gadolinium complex. METHODS: Contrast enhancement was measured on MR in lumbar intervertebral disks for 120 minutes after intravenous injection of gadoteridol or gadopentetate dimeglumine, 0.3 mmol/kg. MR studies were performed with each contrast medium in four rabbits. Contrast enhancement was measured in intervertebral disks as a function of time and contrast medium. RESULTS: With both contrast media, enhancement of normal intervertebral disks was detected. Enhancement of disks was significantly greater with gadoteridol than with gadopentetate dimeglumine. CONCLUSION: The enhancement of cartilage is influenced by the molecular structure of the gadolinium complex. The negative charge of gadopentetate dimeglumine may give it a slower rate of diffusion into disk cartilage than a nonionic complex.

Animals↗

The role of non-adhesive T-cell-accessory cell interactions in the induction of T-cell proliferative hyporesponsiveness.

We have suggested previously that induction of T-cell proliferative hyporesponsiveness is associated with a defective adhesive T-cell-antigen-presenting cell (APC) interaction. In the previous study, the hyporesponsiveness was allospecific, implying that a T-cell receptor-major histocompatibility complex (MHC) interaction had occurred. Therefore, we hypothesized that this type of non-adhesive T-cell-APC interaction might induce T-cell tolerance rather than activation. This hypothesis has now been tested further in the present study, using two experimental approaches. Firstly, L cells, which express a T-cell receptor ligand, i.e. MHC class II molecules, but lack the capacity to bind to T cells and do not express the crucial receptor/counter receptor lymphocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1 (ICAM-1) pair, also induced non-allospecific T-cell proliferative hyporesponsiveness; this was not due to any direct inhibitory effect on the T cells. Secondly, monoclonal antibodies (mAb) directed to LFA-1 and ICAM-1 were used to disrupt T-cell-APC adhesion specifically, while allowing for T-cell receptor-MHC interaction to occur. The results of this new study suggest that the non-allospecific T-cell proliferative hyporesponsiveness induced was a function of direct T-cell inhibitory effects of these mAb. Taken together, these experiments add further evidence to support the notion that accessory cells which engage T-cell receptors without providing the necessary co-stimulatory signals induce T cells which are in a state of functional 'paralysis' with respect to the antigen which the T-cell receptor recognizes.

Animals↗

Contrast enhancement of normal intervertebral disks: time and dose dependence.

PURPOSE: To determine the dose of contrast medium and the imaging strategy sufficient to detect diffusion of low-molecular-weight gadolinium-containing contrast media into normal intervertebral disks. METHODS: In 11 rabbits, sequential MR images were obtained of the spine for 120 minutes after intravenous injection of gadopentetate dimeglumine in doses of 0.1 to 2.8 mmol/kg. Images were inspected for evidence of contrast enhancement. Signal intensity was measured and plotted as a function of time and dose. RESULTS: Contrast enhancement was detected by inspection of images and by measurement in animals receiving doses of 0.3 mmol/kg and larger. CONCLUSIONS: Diffusion of gadolinium-containing chelates into the intervertebral disk can be detected with clinically used doses of commercially available contrast medium. Therefore, with MR and a gadolinium-containing contrast medium, diffusion into intervertebral disks can be studied.

Animals↗

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↗

Induction of adjuvant arthritis in mice.

Adjuvant arthritis, induced by injections of Freund's complete adjuvant into the footpads of some rat strains, has been recognized as a useful animal model for many years. There has, however, been notable lack of success in reproducing this model in other species. We now describe the development of adjuvant arthritis in healthy strain mice approximately 2 months after injection of Freund's complete adjuvant. Although the clinical appearance of the mice and the joint histopathology closely resemble the adjuvant arthritis reported in the rat, we were unable to detect rheumatoid factor in sera from the affected animals. In parallel studies of T cell proliferation, affected animals responded to some mycobacterial antigens but not to the 65-kD heat shock protein of Mycobacterium tuberculosis, suggesting that some other epitope is important in the development of the disease.

Animals↗

Adjuvant composition determines the induction of type II collagen-induced arthritis.

In this study we have investigated the influence of adjuvant composition on the development of collagen-induced arthritis and of anti-collagen type II specific B- and T-cell responses following immunization with type II collagen. DBA/l mice immunized with bovine collagen type II emulsified in complete Freund's adjuvant (CFA) containing Mycobacterium tuberculosis strain H37Ra developed footpad swelling indicative of arthritis. Animals immunized with collagen type II plus CFA containing Mycobacterium butyricum, or incomplete Freund's adjuvant showed no significant increase in footpad width. Induction of anti-CII specific T-cell proliferation was also dependent upon immunization with CII plus CFA containing M. tb H37RA. In contrast, ovalbumin-reactive T-cell proliferation was unaffected by the species of mycobacteria, indicating that the difference in adjuvant activity of the mycobacterial species is specific for anti-collagen type II T-cell responses. Antibody response to collagen type II, unlike T-cell responses, was not significantly different using the two adjuvants. This study therefore demonstrates that murine collagen-induced arthritis requires immunization with collagen type II together with complete Freund's adjuvant containing Mycobacterium tuberculosis H37RA. Since only this combination of antigen and adjuvant induces detectable arthritis and T-cell responses against collagen type II, while antibody synthesis does not have such stringent adjuvant requirements, this suggests that the development of the full pattern of the collagen-induced arthritis disease requires synergistic activation of both humoral and cell-mediated responses.

Adjuvants, Immunologic↗

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↗

Chemically modified antigen-presenting cells induce T lymphocyte allospecific hyporesponsiveness.

We have investigated the interaction between murine T lymphocytes and allogeneic APC in an in vitro proliferative mixed leukocyte reaction. Our results demonstrate that freshly isolated potentially alloreactive murine splenic T lymphocytes, in primary culture, can be induced to develop a state of allospecific proliferative hyporesponsiveness in vitro by exposure to 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide-modified allogeneic APC, a method similar to that previously used to induce nonresponsiveness in murine Ag-specific self-MHC-restricted T lymphocyte clones. This hyporesponsiveness was: specific for the allohaplotype of inducing APC, maintained for 96 h in vitro, not due to cellular inhibitory mechanisms, and associated with reduced ability to secrete IL-2 but not IL-3. Induction of this hyporesponsiveness was not due to altered expression of class II MHC gene products on the APC but was associated with markedly reduced T lymphocyte-APC adhesive interactions despite the lack of a detectable immunophenotypic change in lymphocyte function-associated Ag 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) expression on the modified APC. Therefore, we propose that TCR occupancy in the absence of normal T lymphocyte-APC adhesive clustering may induce T lymphocyte tolerance.

Animals↗

Antigen presentation by dendritic cells provides optimal stimulation for the production of interleukin (IL) 2, IL 4 and interferon-gamma by allogeneic T cells.

Previous studies have shown that dendritic cells are the most potent inducers of T cell proliferation in vitro and that this is reflected in the release of interleukin (IL) 2 into culture supernatants during dendritic cell-T cell interaction. However, the role of the dendritic cells, and, indeed, of the antigen-presenting step, has not yet been explored with respect to other T cell-derived cytokines, in either a qualitative or relative fashion. In this study, therefore, we have examined the comparative role of different antigen-presenting cells (APC) as inducers of T cell cytokine release in allogeneic responses. We have confirmed that dendritic cells are the most effective inducers for IL2 and have shown that this is true not only in primary alloresponses, but also in alloresponder T cells maintained for extended periods and then rechallenged. Dendritic cells were also the most potent inducers of IL3 and interferon-gamma (IFN-gamma) in primary cultures. No IL4 was demonstrable irrespective of the type of presenting cells used, and both tissue macrophages and dendritic cells can induce synthesis of IL6. Likewise, in secondary alloresponses both dendritic cells and to a lesser extent tissue macrophages induce release of IL3, no IL4 is detectable, and activated macrophages and B cells raise IFN-gamma levels in the supernatants albeit to a lower concentration than that seen when dendritic cells are used as stimulators. The results were similar in the tertiary alloresponse except that (a) IL4 was now detectable in the supernatants but only where dendritic cells had been used as APC, and (b) both resting and activated macrophages induced IL2 and IFN-gamma. By the eighth cycle of allostimulation there is negligible IL2. Dendritic cells, tissue macrophages and activated B cells constitute a hierarchy of APC for IL3, IFN-gamma and IL4. These findings therefore demonstrate the role of dendritic cells as potent in vitro inducers of IL3, IL4 and IFN-gamma synthesis as well as of IL2.

Animals↗

Weight of the evidence on the human carcinogenicity of 2,4-D.

The phenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used to control the growth of weeds and broadleaf plants. We convened a panel of 13 scientists to weigh the evidence on the human carcinogenicity of 2,4-D. The panel based its findings on a review of the toxicological and epidemiological literature on 2,4-D and related phenoxy herbicides. The toxicological data do not provide a strong basis for predicting that 2,4-D is a human carcinogen. Although a cause-effect relationship is far from being established, the epidemiological evidence for an association between exposure to 2,4-D and non-Hodgkin's lymphoma is suggestive and requires further investigation. There is little evidence of an association between use of 2,4-D and soft-tissue sarcoma or Hodgkin's disease, and no evidence of an association between 2,4-D use and any other form of cancer. Scientists on the panel were asked to categorize 2,4-D as a "known," "probable," "possible," or "unlikely" carcinogen or as a noncarcinogen in humans. The predominant opinion among the panel members was that the weight of the evidence indicates that it is possible that exposure to 2,4-D can cause cancer in humans, although not all of the panelists believed the possibility was equally likely: one thought the possibility was strong, leaning toward probable, and five thought the possibility was remote, leaning toward unlikely. Two panelists believed it unlikely that 2,4-D can cause cancer in humans.

2,4-Dichlorophenoxyacetic Acid↗

Leprosy in Saudi Arabia, 1986-89.

This study on leprosy includes information obtained from the Ibn Sina Hospital, a specialized centre established 27 years ago for treatment and management of the disease in Saudi Arabia. A total of 792 patients with leprosy were reported during the period of the study (1986-89). A steady decline was observed in the number of patients reported: 432 (54.55%) were non-Saudi and 360 (45.45%) were Saudi. Patients were reported from a total of 22 different countries. The majority of the non-Saudi patients were from the Yemen, 286 (36.11%). The male-to-female ratio was 3.83:1. The age groups comprised: 133 (16.79%), 51 to 80; 575 (72.60%), 21 to 50; and 84 (10.61%), under 20 years of age. The disease was classified into five categories (Ridley and Jopling classification): 295 (37.25%), lepromatous type; 238 (30.05%), tuberculoid type; 146 (18.43%), borderline-tuberculoid type; 29 (3.66%), borderline type; and 84 (10.61%), borderline-lepromatous type. Although the number of registered patients is decreasing, this trend does not suggest an overall decline in the disease in the country. It is recommended, therefore, that the services being provided to patients with leprosy must be integrated with the nationwide network of the Primary Health Care Centres to implement effective control and prevention, including health education for the general population. Furthermore, mutual agreements must be developed with adjacent countries to study the geographic distribution of the disease.

Adolescent↗

Analysis of variation in batches of armadillo-derived Mycobacterium leprae by immunoblotting.

Several batches of cell-free extracts of armadillo-derived Mycobacterium leprae were analyzed by SDS-PAGE and by immunoblotting with monoclonal antibodies. The presence or absence of protease inhibitors had a profound effect on the protein antigens, particularly the 65-kDa antigen. In the absence of protease inhibitors, there were both quantitative and qualitative differences between the different batches of M. leprae extracts.

Animals↗

The Bouveret syndrome: an unusual cause of hematemesis.

Gallstones are usually silent. Less commonly, patients with cholelithiasis develop symptoms and/or complications; biliary fistula occurs in 3% to 5% of the cases. When a large stone is passed and occludes the duodenum, gastric outlet obstruction (the Bouveret syndrome) may result. In reported cases, the stones are usually larger than 2.5 cm. The usual presenting symptoms are those of bowel obstruction: abdominal pain, nausea, and vomiting. Less commonly, the patients experience melena and, rarely, hematemesis. We describe a patient who had the largest stone reported to cause hematemesis rather than bowel obstruction and to be diagnosed endoscopically. The 5 X 4 X 3 cm stone was extracted surgically. Endoscopic diagnosis and extraction of stones up to 3 cm in size has been reported, avoiding the need for surgery.

Aged↗

Peritoneal mesothelioma: an unusual cause of esophageal achalasia.

Secondary esophageal achalasia due to malignancy is a rare condition; only 53 such cases have been reported to date. Sixty-two percent of the cases were due to gastric adenocarcinoma. Mesothelioma of the peritoneum is an uncommon neoplasm. The usual presenting symptoms are abdominal pain, abdominal mass, or abdominal distention. The patient we are reporting had peritoneal mesothelioma which presented with dysphagia and weight loss, in addition to the radiological and manometric picture of achalasia. Secondary achalasia was suspected clinically, and was confirmed by computed tomography and laparotomy. The diagnosis of peritoneal mesothelioma was made only by histopathological examination. We are not aware of any other report documenting the association of peritoneal mesothelioma and achalasia.

Aged↗