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S Ibrahim

Publications and source records attributed to S Ibrahim.

At least 91 records · Page 5Linked to original sources
PubMed1993

Proportion of protein A bindable molecules in human IgM and IgA antibodies to seven antigens.

Human IgM or IgA antibodies to seven antigens (tetanus and diphtheria toxoids, and five bacterial polysaccharides) were studied by determining what proportion of these antibodies were bound by staphylococcal protein A. This alternative binding is a marker of VH genes of family 3. Each response was studied in an average of nine individuals. The binding proportion of antibodies to the two toxoids resembled that of total serum immunoglobulins; 13-14% of IgA and 40% of IgM antibodies were bound by protein A. All anti-polysaccharide antibodies had higher proportions of protein A bindable molecules than serum IgM or IgA indicating a bias for VH genes. This excess was high in antibodies to Haemophilus influenzae type b (Hib) and pneumococcal type 14 polysaccharides (> two-fold). It was moderate but statistically significant in antibodies to pneumococcal types 18C and 3 capsular polysaccharides and to C polysaccharide. All vaccinated Finns exhibited the VH3-preference in antibodies to Hib and type 14 polysaccharide.

Adult↗
PubMed1993

The pattern and phenotype of T-cell infiltration associated with human liver allograft rejection.

Although transplant biopsy remains the best means for assessing liver allograft dysfunction, the presence and degree of rejection often is difficult to determine by current histologic criteria. The added diagnostic and prognostic value of examining liver allograft biopsy specimens by immunopathologic methods, such as phenotyping inflammatory cell infiltrates, has been inconclusive. To examine the value of assessing the phenotype and location of T-cell infiltrates we compared findings in 20 liver transplant biopsy specimens obtained from patients undergoing allograft rejection with those in 20 biopsy specimens from patients with no evidence of rejection. Serial frozen sections from all biopsies were labeled by immunoperoxidase techniques using monoclonal antibodies to identify cells expressing CD3, CD4, CD8, CD45RA, and CD45RO. As expected, the median of average cell infiltrates was higher in the rejecting versus nonrejecting group for each cell phenotype and region. However, statistical comparisons indicated that only some combinations of cell phenotype and location were significantly greater in the rejecting versus nonrejecting groups. The median number of portal CD3+ T cells per high-power field was increased in the rejecting versus nonrejecting groups (15.15 v 5.00 cells/high-power field; P < .01). This primarily was the result of a significant increase in CD8+ cells (7.15 v 1.55 cells/high-power field; P < .0001). Examination of cells expressing CD45 isoforms also revealed a suggested increase (P < .04) in CD45RO+ "memory" but not in CD45RA "naive" T cells infiltrating portal areas. In lobular areas cell infiltrates of any examined phenotype were not significantly increased in the rejecting versus nonrejecting groups. These findings indicate that during liver allograft rejection the most characteristic changes involve an increase in T cells infiltrating the graft in portal regions and suggest that human liver allograft rejection preferentially involves memory CD8+ T cells directed at portal structures.

Antigens, CD↗
PubMed1993

Characterization of T cells expressing the gamma/delta antigen receptor in human renal allografts.

To investigate the role of gamma/delta+ T cells in allograft rejection, we have studied the TCR phenotype and function of lymphocytes infiltrating rejecting, rejected, and nonrejecting human renal allografts. Two-color immunohistologic staining showed that 19% of rejecting biopsies and 40% of rejected nephrectomies had significant infiltration (> 10% of the total T-cell population) with gamma/delta+ T cells. No biopsies from nonrejecting kidneys showed > 10% gamma/delta+ T cells. Flow-cytometry analysis of T-cell populations expanded from rejecting and rejected allografts demonstrated that 33% of biopsy- and 40% of nephrectomy-derived populations had significant percentages (> 10%) of gamma/delta+ T cells. Six cell lines with increased numbers of gamma/delta+ T cells were tested for cytolytic activity against the NK target cell line K562 and compared with cytotoxic activity of exclusively alpha/beta T-cell populations. Lysis was noted by all gamma/delta+, but no gamma/delta-, populations. To confirm that the cytotoxicity of these gamma/delta+ T-cell populations was not MHC directed, one nephrectomy-derived population with 69% gamma/delta+ T cells by cytometry and > 50% by immunohistology was studied extensively. High levels of killing were seen against the NK targets K562 and Daudi as well as other malignant, benign, and third-party renal cell lines, but relevant alloantigen-expressing targets were not killed. Sterile cell sorting was used to isolate the gamma/delta+ T cells. The gamma/delta+ cells displayed enhanced killing of K562 while the gamma/delta- cells showed no cytolytic activity. Cytotoxicity mediated by gamma/delta+ T cells was also demonstrated against donor-derived, untransformed renal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity, Immunologic↗
PubMed1993

Immunoglobulin binding specificities of the homology regions (domains) of protein A.

Protein A binds immunoglobulins and it has two target structures, one in Fc gamma (CH) and the other in selected VH regions. The protein has five homology regions (domains), A, B, C, D, and E. Fc-binding and VH-binding have been reported to be non-competitive, suggesting that different domains are responsible for the binding of the two ligands. On the other hand, all five domains have been reported to bind Fc. I studied binding of different immunoglobulins by protein A or its domain B (rBB). The results show that separate domains bind VH and Fc. If all five domains are capable of binding Fc, the ones that bind VH have low affinity for Fc. Furthermore, the number of Fc-binding domains varies depending on the type of the IgG being bound. Human IgG1 or IgG2 or rabbit IgG (Fc) seem to be bound by several domains (possibly four), and domain B is one of them. Mouse IgG1 or IgG2b are bound by fewer domains not including B. Murine IgG2a is also bound by fewer domains but B is one of them.

Animals↗
PubMed1993

The alternative binding site for protein A in the Fab fragment of immunoglobulins.

Twenty-six new human or murine monoclonal immunoglobulins (IgM, IgA, murine IgG1 or human IgG3) with a known V-region sequence were tested for alternative (non-Fc) binding to Staphylococcal protein A. Seven of them did not bind at all. Four immunoglobulins (all mouse IgG1) were bound but easily eluted (at pH 6). They were probably bound via the Fc part. All eleven were classified as negative for alternative binding. Fifteen immunoglobulins were found to bind more firmly; they came off the protein A column at pH 4-3 (alternative binders). Amino acid sequences of immunoglobulins that have been typed in the present work or earlier (25 binders and 26 non-binders) were compared. The light chain, the C region of the heavy chain and the D and JH segments look irrelevant for alternative binding. The N-terminal portion (amino acids 1-94) of the H chain probably forms the ligand of protein A. A peptide making the ligand cannot be reliably localized within this stretch but binder proteins had a high homology in residues 6-29. All mouse immunoglobulins expressing VH genes of families J606 or S107 were alternative binders; those expressing other families were non-binders.

Amino Acid Sequence↗
PubMed1993

Once-a-day administration of amikacin in neonates: assessment of nephrotoxicity and ototoxicity.

Neonates, especially preterms, are known to have low glomerular filtration rates (GFR). This may result in elevated trough concentrations during multiple administration of aminoglycosides (AGs), potentially leading to nephro- and ototoxic reactions. The once-daily administration (q.d.) of AGs has been shown to be equally or better tolerated in adults and children than the conventional schedules (twice daily, b.i.d.; thrice daily, t.i.d.), while offering potential pharmacodynamic and nursing advantages. No data, however, are available for neonates. As a consequence, this pilot study was conducted in order to assess the tolerance of the once-a-day administration of amikacin in comparison with the twice daily dose regimen, in relation to the pharmacokinetics of the drug under these two schedules. 22 Male neonates (gestational age > or = 34 weeks; postnatal age < or = 2 days) were randomized to receive amikacin (AK) (15 mg/kg/day) q.d. (n = 10) or b.i.d. (n = 12) together with ampicillin (50 mg/kg/12 h). AK plasma levels were measured at days 1, 3, 5 and 7 of treatment just before the next dose (trough level) and 1 h after completion of infusion (peak level) and after 3 and 6 h only at day 1. Due to the small size of the samples, no difference in efficacy could be assessed and was not the aim per se. Glomerular dysfunction was assessed by creatinine clearance, and tubular injuries by the urinary excretion of proteins (retinol binding protein, beta 2-microglobulin, clara cell protein (P1) and microalbumin), enzymes (N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, alanine aminopeptidase, and gamma-glutamyltransferase), and total phospholipids (TPL) in urine. Ototoxicity was assessed by brainstem auditory evoked potentials (BAEPs) at days 0, 3 and 9 of therapy. Eight healthy neonates served as controls. All patients showed a normal and similar increase of GFR during the first postnatal days. Proteinuria did not increase, but enzymuria and TPL increased significantly during the treatment in both AK groups without significant difference between groups. BAEPs at day 9 were not significantly different between treated and untreated patients. We conclude from this pilot study that, in the absence of more toxicity, the q.d. administration of AK in neonates of > or = 34 weeks of gestational age may be recommended over its bid schedule in view of its potential advantages.

Amikacin↗
PubMed1993

Differential infiltration by CD45RO and CD45RA subsets of T cells associated with human heart allograft rejection.

Subsets of T cells express different isoforms of the leukocyte common antigen CD45; those expressing the glycoprotein 220 isoform (CD45RA) have been characterized as naive in their response to antigens, and those expressing the glycoprotein 180 isoform (CD45RO) as memory T cells. The association between the rejection status of human cardiac allograft recipients and the relative infiltration of the CD45 subsets of both CD8+ and CD4+ T cells was examined using two-color immunohistological labeling techniques on 33 heart transplant biopsies, categorized by routine histological and clinical criteria as mild (requiring no treatment) or moderate (requiring antirejection therapy) rejection. Double-labeling was performed using pairs of monoclonal antibodies to define the following populations: CD4+ CD45RA+, CD4+ CD45RO+, CD8+ CD45RA+, and CD8+-CD45RO+. The number of cells per high-power field (HPF) for each of these cell subsets was counted in every biopsy. In cases with mild rejection, infiltration was predominant for CD4+ CD45RA+ cells (median = 5.0 cells/HPF) relative to CD4+ CD45RO+ (3.12 cells/HPF), CD8+ CD45RA+ (2.14 cells/HPF), and especially CD8+ CD45RO+ (1.22 cells/HPF) populations. In cases with moderate rejection, all four subpopulations increased but were essentially equivalent in intensity, such that in comparison to cases with mild rejection, the smallest increase was seen for CD4+ CD45RA+ cells (6.67 cells/HPF, P < 0.09) and the greatest for CD8+ CD45RO+ cells (7.00 cells/HPF, P < 0.002). A majority of CD8 cells expressed CD45RA in 14 of 16 (88%) cases of mild rejection compared to only 2 of 17 cases of moderate rejection. Moreover, the ratio of CD45RO+ to CD45RA+ cells in each biopsy was higher in moderate versus mild rejection for both CD4 (median ratios = 1.13 versus 0.68, respectively; P < 0.008) and CD8 (1.43 versus 0.58, respectively; P < 0.005) subsets. A majority of T cells expressed CD45RO in cases of moderate rejection (11 of 14 or 79%), compared to only 1 of 13 (8%) cases of mild rejection. These findings indicate that during generally self-limited mild acute cardiac allograft rejection there is a predominance of naive CD45RA+ T cells, especially of the CD4 phenotype, whereas during moderate rejection there is a significant shift toward activated CD45RO+ T cells, especially in the CD8 population.

Biopsy↗
PubMed1992

Brain Na+ K+ ATPase and cholesterol in acute experimental trypanosomiasis.

Brain Na+ K+ ATPase activity has been found to decrease in experimental trypanosomiasis in rats infected with Trypanosoma congolense. Some physical features that affect membrane fluidity were also observed to be altered. The levels of cholesterol in the brain and free fatty acids in the serum were found to increase in the infected animals. These findings might be relevant to the development of brain lesions.

Animals↗
PubMed1992

Comparative assessment of poly-L-aspartic and poly-L-glutamic acids as protectants against gentamicin-induced renal lysosomal phospholipidosis, phospholipiduria and cell proliferation in rats.

Coadministration of poly-L-aspartic acid (poly-L-Asp) protects rats against all measured signs of aminoglycoside nephrotoxicity. Based on in vitro and acute in vivo models, previously we hypothesized that poly-L-Asp protects by forming complexes with the drug in lysomes of proximal tubular cells. However, another closely related peptide, poly-L-glutamic acid (poly-L-Glu), could not protect against gentamicin-induced phospholipidosis and nephrotoxicity, presumably because it is susceptible to rapid hydrolysis in sysosomes in vivo. The present study expands the in vivo comparison between these two polyanions to a subacute model of rats and examines in detail the influence of these polymers on the qualitative and quantitative morphological alterations of lysosomes, phospholipiduria and proliferation of cortical cells induced by gentamicin. Our results not only demonstrated that despite a significantly higher drug cortical accumulation, the coadministration of poly-L-Asp almost completely protects against the development of all these early renal alteration but also pointed to the possibility of a mild, albeit apparently nonlethal, lysosomal thesaurismosis to develop under these conditions. In contrast, poly-L-Glu could not protect against these early renal alterations, though cortical drug accumulation was not significantly higher; however, it induced a conspicuous proliferation of peritubular interstitial cells. Therefore, the present work, taken together with the earlier results of ours as well as that of others, tends to strengthen the hypothesis that the site of action of poly-L-Asp must be in lysosomes, which are also the organelles that sequester and accumulate the drug.

Animals↗
PubMed1991

Empirical antimicrobial therapy with a single daily dose of ceftriaxone plus amikacin in febrile granulocytopenic patients: a pilot study.

The optimal management of fever in granulocytopenic patients remains controversial. This pilot study investigated the potential value of single daily doses of amikacin administered empirically with ceftriaxone in febrile granulocytopenic patients. None of the patients died as a result of infection or toxicity from the prescribed regimen. Serum concentrations failed to show drug accumulation. Modifications of empirical antimicrobial therapy were made at a similar rate to other conventional regimens. Vancomycin seemed to increase the incidence of nephrotoxicity. Overall, this pilot study suggests that empirical therapy with single daily doses of amikacin plus ceftriaxone is safe and effective and should be further investigated in a larger number of patients.

Adolescent↗
PubMed1991

Pharmacodynamic parameters and toxicity of netilmicin (6 milligrams/kilogram/day) given once daily or in three divided doses to cancer patients with urinary tract infection.

The pharmacologic parameters and toxicity of netilmicin (6 mg/kg/day) given once daily (qd) or thrice daily (tid) for the treatment of urinary tract infections were studied in a randomized prospective study of 60 cancer patients. The overall efficacy was 96%. Nephrotoxicity, assessed by the measure of urinary excretion of phospholipids, was lower for the patients receiving the qd regimen than for those receiving the tid regimen. Elevation of serum creatinine (20% over baseline) occurred in one patient receiving the qd regimen and in three receiving the tid regimen. Cochleotoxicity, assessed by pure-tone audiometry (250 to 18,000 Hz) occurred in one patient receiving the qd regimen and none receiving the tid regimen. Concentrations in sera were measured on days 1 and 5. No significant accumulation was observed in either group. Median serum bactericidal titers, expressed as reciprocal values (percentage of the sera with a titer greater than or equal to 8), were measured against 25 test organisms in samples collected 6 h after the administration of netilmicin and were, for the qd group, 16 (82%) against members of the family Enterobacteriaceae and less than 2 (8%) against Pseudomonas aeruginosa, and for the tid group, 4 (57%) against members of the Enterobacteriaceae and less than 2 (0%) against P. aeruginosa. The rate of killing in serum was rapid (2 to 3 log in 2 h against P. aeruginosa; 3 to 5 log in 2 h against members of the Enterobacteriaceae) and correlated with the sampling time and hence the concentration in serum of netilmicin. The duration of the postantibiotic effect in serum depended also on the strain and the sampling time of the serum.

Adult↗
PubMed1991

KAP study on mothers of children with Down syndrome.

We evaluated 50 mothers of children with Down syndrome attending Genetic Clinic of the Institute of Child Health and Hospital for Children, Madras, with special reference to their knowledge, belief and attitudes in the care of these children. After evaluation, they were educated individually and in groups with demonstration, picture cards and pamphlets, on the causation, expected health problems, developmental potential of Down syndrome and the ways and means to help the child to attain the maximum developmental potential. They were taught on preventive aspects of Down syndrome as well. Re-evaluation was done after three months, and considerable improvement was noted in the mother's knowledge, and attitude towards bringing up such a child. The mothers also showed an improvement in the skills in providing developmental enrichment to these children. Thus this study has formulated a programme in the management of such children, which can be practised on any population, anywhere, especially, in rural areas, and by less affluent folk, with poor educational background.

Adult↗
PubMed1990

Mouse Ig coded by VH families S107 or J606 bind to protein A.

Twenty-five monoclonal mouse Ig (5 IgA, 7 IgM, and 13 IgG1) were tested for binding to staphylococcal protein A. They were allowed to attach to protein A Sepharose column at pH 8.0 and were then eluted with a pH gradient from approximately 7.5 to 3.0. Five of them (IgM or IgA) did not bind. Ten came off with pH approximately 6. They were all IgG1, and were probably bound (weakly) via the Fc portion. The remaining 10 (3 IgA, 4 IgM, and 3 IgG1) were more firmly bound; they came off with pH-values ranging from 5.0 to 3.5. They all expressed VH genes of families J606 or S107, whereas all the 15 Ig that were not firmly bound expressed VH genes of six other families. The VL domains seem to be unimportant for protein A binding inasmuch as a firmly binding and a weakly binding IgG1 antibody share identical VK domains. VH sequences of protein A-binding and nonbinding Ig were compared. No likely peptide sequences were found that might make the ligand for protein A.

Amino Acid Sequence↗
PubMed1990

Increased levels of protein- and lipid-bound sialic acids in the renal cortex of rats injected with low doses of gentamicin.

Administration of the aminoglycoside antibiotic, gentamicin, even at therapeutic doses, causes renal lysosomal phospholipidosis. We now report that protein- and lipid-bound sialic acid levels are increased significantly in a time-dependent fashion in the renal cortex of rats injected with gentamicin (10 mg/kg body wt. per day) for 4-10 days and a significant relationship could be observed between these two parameters. This elevation was not due to tissue regeneration, since it was not observed in cisplatin-treated animals.

Animals↗
PubMed1990

Inhibition of aminoglycoside-induced nephrotoxicity in rats by polyanionic peptides.

In the present study, we compared poly-L-Asp with poly-L-Glu and poly-D-Glu in vitro and in vivo for their ability to inhibit the GM-induced nephrotoxicity. In vitro, all three polyanions (i) bound GM over a wide range of pH; (ii) displaced GM previously bound to negatively charged phospholipid bilayers at acid pH (i.e. under the conditions prevailing in lysosomes in vivo), and thereby (iii) decreased the inhibitory potency of GM towards lysosomal phospholipase A1. Thus, one was tempted to predict that all three polyanions would have the potential of protecting against AG-induced nephrotoxicity. However, when co-administered to rats with GM, poly-L-Asp and poly-D-Glu completely suppressed the development of lysosomal phospholipidosis, as assessed by biochemical criteria and increased drug accumulation, whereas poly-L-Glu did not offer such protection despite a relatively lower increase in drug accumulation levels. Histoautoradiography also confirmed that poly-L-Asp, but not poly-L-Glu, was a nephroprotectant against the tissue proliferative response induced by GM. Morphologically, poly-L-Asp almost completely and poly-D-Glu totally prevented the accumulation of myeloid bodies in lysosomes. In vitro incubation in the presence of purified lysosomal extracts revealed marked differences in the hydrolysis rate of these peptides (poly-D-Glu:poly-L-Asp:poly-L-Glu = 1:1.2:16.9). Assuming that all three polyanionic peptides are transported and accumulated in lysosomes to the same extent, these results not only suggest that their stability in lysosomes is an essential requisite for protection against lysosomal phospholipidosis, but also strengthen our hypothesis that the site of action of poly-L-Asp is inside the lysosomes but not at the level of the renal membranes. In addition, poly-D-Glu alone or combined with GM induced another type of morphological lesion, not related to AG-induced nephrotoxicity which, to our knowledge, has not yet been described.

Animals↗
PubMed1990

Safety, pharmacokinetics and efficacy of once-a-day netilmicin and amikacin versus their conventional schedules in patients suffering from pelvic inflammatory disease.

The safety, pharmacokinetics and efficacy of one daily injection (qd) of amikacin (AK) and netilmicin (NT) was compared with the recommended schedules (cs), i.e. twice-daily or thrice-daily, respectively. Women (17-43 years, n = 78) suffering from pelvic inflammatory disease were randomly assigned to qd or cs of either AK (14 mg/kg per day) or NT (6.6 mg/kg per day). Biometric parameters were similar in the 4 groups and all patients received ampicillin (4 g/day) and tinidazole (0.8 g/day). The Repeated Measures Analysis of Variance was used to distinguish the effects of the schedules and of the drugs choice on critical parameters. Efficacy was similar in the 4 groups and not influenced by the schedule of administration. No significant differences in nephro- and oto-toxicity were observed as assessed by serum creatinine and losses of hearing at low frequencies, but early phospholipiduria and auditory losses at high frequencies were significantly reduced with the qd administration compared to cs and by AK compared to NT. These data suggest that the qd schedule of AK and of NT is as efficacious as their cs schedules, and causes less renal and auditory alterations.

Amikacin↗