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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

Magnetic resonance imaging relaxation times and gadolinium-DTPA relaxivity values in human cerebrospinal fluid.

RATIONALE AND OBJECTIVES: This study was conducted to prove the feasibility of using cerebrospinal fluid (CSF) T1 and T2 measurements to assess the blood-brain barrier integrity in disease states not noted for focal blood-brain barrier disruption, such as Alzheimer's disease. METHODS: T1 and T2 of human CSF samples were measured with and without gadolinium Gd-DTPA over a concentration range of 1.98 x 10(-3) to 6.32 mM, in a GE 1.5-T Signa scanner. RESULTS: T1 and T2 of human CSF without Gd-DTPA were measured as 2.39 and 0.23 s. K1 and K2 were calculated as 6.25 and 6.74 mM(-1) s(-1). The lowest Gd-DTPA concentration with measurable T1 and T2 was 1.98 x 10(-3) mM. There is no statistically significant difference in T2 and K2 at different repetition times. CONCLUSIONS: This work demonstrates that a single measurement of relaxation times after contrast-enhanced magnetic resonance imaging could be used to determine the Gd-DTPA concentration in CSF. It may thus be feasible, using this technique, to measure intersubject and intraregional variability in the quantity of Gd-DTPA transferred across the blood-brain barrier after intravenous injection of contrast agent.

Blood-Brain Barrier

Purification and characterization of a novel acid-soluble nuclear protein from developing embryos of the camel tick Hyalomma dromedarii (Acarina: Ixodidae).

A novel acid-soluble protein has been extracted from nuclei of developing embryos of H. dromedarii ticks and purified to homogeneity. This tick embryo basic protein (TEBP) was predominant during the cleavage stage of tick embryogenesis, whereas the complete set of histones was detectable at the late cleavage stage. The amount of TEBP reaches a maximum value at day 9 after oviposition. Thereafter, the original N-terminal dipeptide (leucine-serine) is eliminated. This coincides with the start of organogenesis. In spite of its low molecular mass, TEBP seems to be related to histone H1 in some properties such as solubility in perchloric acid and binding affinity to DNA. A task for the future will be to define the role of this protein as a counterpart of the histones for the genome organization during embryogenesis.

Amino Acid Sequence

Evaluation of early (5 to 6 hours) iodine 123 uptake for diagnosis and treatment planning in Graves' disease.

BACKGROUND: Twenty-four-hour radioactive iodine uptake measurements necessitate extra visits and time delays in diagnostic confirmation of and therapy planning for hyperthyroid patients. We evaluated the early (5 to 6 hours) measurement of iodine 123 uptake (EU) to predict late (24 hours) uptake (LU) and assessed its value in the management of hyperthyroidism. METHODS: We conducted a prospective study in 51 previously untreated hyperthyroid and 27 euthyroid patients (initial evaluation group). Patients underwent both 6- and 24-hour 123I uptake measurements. A subsequent 21 patients with Graves' disease (confirmation group) were evaluated in light of regression data generated in the initial evaluation group. RESULTS: An EU value of greater than 20% had a sensitivity of 100%, a specificity of 96%, and a positive predictive value of 98% for the diagnosis of hyperthyroidism and was superior to the most predictive LU value (> 30%), which had a sensitivity of 98%, a specificity of 89%, and a positive predictive value of 94%, in distinguishing the hyperthyroid patients from euthyroid patients or those with subacute thyroiditis. Regression analysis revealed that the 24-hour uptake of the hyperthyroid patients could be predicted from the early measurement with the following formula: LU = 28.94 + 0.584 (EU). The measured EU of the confirmation group was used to calculate a predicted LU with use of this formula. Measured LU and predicted LU correlated well (r = .85, P < .001). Iodine 131 dose calculations were performed post hoc; LU calculated doses correlated with predicted LU doses (r = .91, P < .001). Mean dose differences were small. CONCLUSIONS: The EU of 123I can replace 24-hour uptake measurements. Early uptake measurement is reliable and clinically useful for diagnosis confirmation and treatment planning in thyrotoxic patients.

Adolescent

The injured cell: the role of the dendritic cell system as a sentinel receptor pathway.

A major unresolved paradox in immunology remains: how do we avoid harm, despite the abundant opportunities for induction of immune responses against self-proteins? Here, Mohammad Ibrahim, Benjamin Chain and David Katz extend Janeway's proposed explanation, arguing that adaptive immune responses are initiated not only by conserved microbial products, but also by microenvironmental tissue injury. They suggest that the key step is local dendritic cell activation, followed by upregulation of T-cell costimulatory molecules on these cells, and migration, leading to antigen presentation.

Allergens

In situ extracorporeal shock wave lithotripsy (ESWL) for the management of primary ureteric calculi in children.

Lithotripsy was used to treat 19 children (3 to 16 years of age) with primary ureteric calculi. No attempts were made to mobilize the stones to the kidney. Stones were located in the upper ureter in seven patients, middle ureter in three, and lower ureter in nine. Stone size ranged from 5 to 25 mm (average, 10.4 mm). All treatments were performed in the outpatient unit. Two children required general anesthesia, and 17 received intravenous sedation. The mean amount of energy used was 17.8 kV, and the average number of shock waves was 5,489. Before commencement of lithotripsy, two patients needed ureteric catheterization, and two had placement of double pigtail catheters. Of the 18 children who had adequate follow-up, 17 (94.4%) were completely stone-free, without any complication. The authors conclude that in situ extracorporeal shock wave lithotripsy is a safe and effective method for the treatment of primary ureteric calculi in children.

Adolescent

In situ extracorporeal shock wave lithotripsy for primary ureteric calculi.

OBJECTIVE: To determine the efficacy of the Lithostar lithotriptor for the in situ treatment of primary ureteric stones. METHODS: We reviewed, retrospectively, our experience with 283 patients with primary ureteric stones treated with extracorporeal shock wave lithotripsy (ESWL) using the Lithostar lithotriptor. No attempts were made to manipulate the stones. The majority of the patients were treated using only intravenous analgesia. Auxiliary measures were used in 84 patients (29.6%). There were 112 patients (39.6%) with upper, 53 (18.7%) with middle, and 118 (41.7%) with lower ureteric stones. RESULTS: A single ESWL session was needed for 200 patients (70.6%), two for 49 patients (17.3%), and more than two sessions for 34 patients (12%). Of the 248 patients who had adequate follow-up, 220 (88.7%) were stone free, 14 (5.65%) had some residual stone, while 14 (5.65%) patients failed to respond to the treatment. Patients' gender and body weight influenced the treatment and the clearance rate numerically without any statistical significance. The stone site was the most significant factor influencing the final result. Stones larger than 10 mm and the presence of hydronephrosis adversely affected the treatment. CONCLUSIONS: In situ ESWL of ureteral stones with the Lithostar device is a convenient and efficient method of treating calculi within the whole length of the ureter without the need for any manipulation.

Adolescent

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