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S S Asghar

Publications and source records attributed to S S Asghar.

At least 19 recordsLinked to original sources
PubMed1992

Molecular heterogeneity of the fourth component of complement (C4) and its genes in vitiligo.

In view of evidence suggesting vitiligo is an autoimmune disease, we investigated whether vitiligo is associated with inherited deficiencies of the fourth (C4) and second (C2) component of complement and with certain human leukocyte antigens (HLA). Analysis of functional activities of C4 and C2 in sera of patients with vitiligo (n = 42) showed that 17% of them had a heterozygous C4 deficiency and 5% had a heterozygous C2 deficiency. In the normal control group (n = 30), 3% had a heterozygous C4 deficiency and none had a C2 deficiency. C4 typing by Western blot analysis showed the frequency of the C4A*Q0 allele in the vitiligo patient group to be close to normal. However, the frequency of one C4B*Q0 allele was three times higher, and that of two C4B*Q0 alleles five times higher in the vitiligo patient group than the reported frequencies in normal control groups. Southern blot analysis of Taq1 digests of DNA using C4 and 21-hydroxylase probes showed that two patients with two C4B*Q0 alleles had a deletion of a 21-OHA-C4B segment. In the other patients, having one or two C4B*Q0 alleles, these null alleles probably occurred due to a loss of C4 gene expression. HLA analysis did not show any allelic association of C4A*Q0 or C4B*Q0 with any HLA antigen in vitiligo, but confirmed the previous findings of a negative association with HLA-DR3 and a positive association with HLA-DR4. These results suggest that abnormalities of the C4B gene and the above-mentioned associations with HLA antigens may be some of the risk factors in vitiligo.

Adrenal Hyperplasia, Congenital↗
PubMed1992

CD59: a molecule involved in antigen presentation as well as downregulation of membrane attack complex.

CD59 is a recently discovered complement (C) regulatory protein. Three activities of CD59 have been recognized so far. It can downregulate the activation of the C cascade at membrane attack complex formation stage, it participates in T-cell rosette formation with erythrocytes and appears to be necessary for T-cell activation. CD59 is broadly distributed on cells of various organs and this is compatible with its function of protecting cells and tissues from incidentally activated autologous C. CD59 is encoded by a single gene residing on chromosome 11. The entire sequence of CD59 cDNA is known, from which the amino acid structure of CD59 has been deduced. Mature CD59 is made up of 103 amino acids. It has two potential N-glycosylation sites. Carbohydrate constitutes about 20% of the molecular mass of CD59. The protein part of the molecule is covalently linked to an oligosaccharide which, in turn, is glycosydically linked to phosphatidylinositol (PI). CD59 is anchored to the cells via PI moiety. The fine structure of the PI anchor of CD59 has not yet been established. Decreased expression of CD59 has been shown in two diseases. In paroxysmal nocturnal hemoglobinuria, erythrocytes (type III) lacking CD59 (and other PI proteins) have susceptibility to lysis by membrane attack complex. In psoriasis, expression of CD59 (and CD55) is drastically decreased in psoriatic lesions, presumably due to PI cleavage involving signal transduction mechanism(s) leading to increased proliferation of various cell types in lesional skin.

Amino Acid Sequence↗
PubMed1991

Hereditary deficiency of C5 in association with discoid lupus erythematosus.

A 29-year-old woman with discoid lupus erythematosus had undetectable classic pathway complement activity. Hypocomplementemia was due to selective deficiency of C5. One of her children was also deficient. To our knowledge this is the first documented case of an association between discoid lupus erythematosus and C5 deficiency.

Adult↗
PubMed1991

Effects of renal failure on complement C3d levels.

Elevated plasma concentrations of complement split product C3d have been reported to represent activation of the complement system. In the present study the effect of renal function on C3d concentrations was investigated in patients with various degrees of renal impairment, in patients with chronic renal failure and in CAPD patients. It appeared that elevated plasma C3d concentrations were present in patients with plasma creatinine concentrations in excess of 200 mumol/l regardless of the type of kidney disease. It is very likely that this can be attributed to renal handling (i.e. glomerular filtration, tubular reabsorption and renal catabolism) of C3d in a similar way as has been demonstrated for other low molecular weight proteins. The peritoneal permeability to C3d was slightly less than could be expected on the basis of its molecular weight without evidence of local production of C3d. Renal function should be taken into account in the interpretation of elevated plasma concentrations of C3d.

Complement Activation↗
PubMed1991

Suppression of vascular injury at the Arthus reaction site by a complement inhibitor, 5,5',5''-(1,3,6-naphthalene-triyl-tris[sulfonylimino])-tris (1,3-benzene disulfonic acid) hexasodium salt.

A novel polyanionic complement inhibitor 5,5,5''-(1,3,6-naphthalene-triyl-tris[sulfonylimino])-tris(1 ,3-benzene- disulfonic acid) hexasodium salt (compound IIb) was tested for its ability to suppress vascular injury at the site of the Arthus reaction (AR). In control animals in which AR was evoked without drug treatment, venules at AR sites ranged from normal (arbitrarily defined as stage I) to destroyed (stage V). Between these two ends of the spectrum were venules with an accumulation of cells and deposits of electron dense material (stage II), accumulations of cells and deposits and small endothelial gappings (stage III), and accumulations of cells and depositions which had spread into perivascular tissue and small gappings (stage IV). In animals treated with compound IIb, the AR stopped at stage III or IV depending on the dose, it never reached stage V. In other words compound IIb treatment resulted in protection of endothelium, basal lamina and other structures from the destruction which is characteristically observed in the AR. The effect of high doses of compound IIb was similar to that described before for suramin.

Animals↗
PubMed1990

Inhibition of cellular infiltration at the site of Arthus reaction by chlorpromazine. Use of a new area integration technique.

Chlorpromazine, an inhibitor of the complement (C) system, inhibited the cellular infiltration at the site of Arthus reaction (AR), as assessed by a newly developed computerized area integration technique (CAIT). This inhibition was rather strong (mean value 92%) and statistically significant according to the classical quotient estimator. This may, at least in part, explain the protection of vessel wall destruction by chlorpromazine in AR, as observed in a previous study. CAIT estimated cellular infiltration in H & E stained skin biopsy sections quantitatively and reliably.

Animals↗
PubMed1989

A new method for the estimation of C3d. Affinity clearance of C-determinant-bearing C3 molecules and fragments followed by estimation of C3d by ELISA.

A method is described to quantitate human complement fragment C3d. Test samples were treated with a predetermined excess of anti-C3c-Sepharose beads in the presence of EDTA to remove all the C-determinant-bearing C3 molecules or fragments. C3d left in the supernatant was then estimated by ELISA. Using this method, C3d could be estimated accurately in normal plasma samples. A good correlation (r = 0.93) was observed between C3d values obtained by this method and values obtained by the widely used method of Perrin and coworkers. The average C3d plasma concentration was 2.8 mg/l (SD = 0.7 mg/l, n = 21). The interassay coefficient of variation using a normal plasma pool (C3d 2.7 mg/l) was 8.3% and using normal plasma pools in which the C3d concentrations were raised to 10.3 and 17.4 mg/l by the addition of aged normal serum the levels were 8.0 and 7.5% respectively. Intra-assay coefficients of variation with these samples were 4.6, 3.0 and 2.8%, respectively. 16 patients with renal dysfunction had C3d levels in the range of 4.3-10.0 mg/l and 15 patients undergoing continued ambulant peritoneal dialysis had levels of 3.3-12.2 mg/l. The C3d content in peritoneal dialysate of patients undergoing dialysis varied from 9.3 to 383 micrograms/l.

Antibody Specificity↗
PubMed1989

Large-scale cultivation of human melanocytes using collagen-coated Sephadex beads (cytodex 3).

Pure melanocytes were obtained from the epidermis of human foreskin by a modification of a previously described method in which geneticin was added for selective killing of fibroblasts. Purity of the culture was confirmed by light and electron microscopy and by the use of a monoclonal antibody NKI-beteb, which is specific for a vesicular membrane antigen present on melanocytes. Melanocytes were tested for their affinity to several microcarriers. They attached to cytodex 1 and 3 and dorma cell, but they did not attach to glass and gelatin beads. The best results were obtained with cytodex 3. After an almost immediate and total attachment of melanocytes a fourfold to fivefold increase in cell number was achieved on this microcarrier within 3 weeks. With the results obtained, it seems that the collagen-coated cytodex 3 microcarrier surface supports the growth of melanocytes. Preliminary results obtained with a microcarrier cell culture fermenter clearly indicate that the large-scale cultivation of normal human melanocytes in such an automated system is possible.

Cell Adhesion↗
PubMed1988

A new approach to immunosuppression at the complement level-hypothesis.

A conceptual hypothesis for the possibility of treatment of certain immunological diseases in which the classical pathway (CP) of complement (c) plays a role in the pathogenesis is presented. It is proposed that in the clinical situations in which CP activation primarily contributes to the disease activity, administration of F(ab)2 fragment of human monoclonal antibodies directed against the active site of human Cls may suppress the disease. The F(ab)2 fragment should be specific for the active site of Cls and should not be reactive with the rest of the molecule. Such a treatment is not likely to effect Cls or total CP levels, as the F(ab)2 fragment will react only when and as soon as the active site has been generated on a Cls molecule. The interaction of a F(ab)2 fragment with Cls is also not likely to cause activation of the C. Specific inhibition of Cls in this way is expected to prevent, in CP mediated diseases, the increase in vascular permeability due to Cls and generation of C fragments responsible for anaphylactic, chemotactic and exocytosis activities and thus suppression of tissue destruction and disease activity. The validity of this hypothesis could be tested in experimental models of C mediated diseases in rats using F(ab)2 fragments of rat monoclonal antibodies directed against rat Cls. These studies could also be carried out in mouse system. F(ab)2 fragments of monoclonal antibodies against the active site of Clr may also be used instead of those against Cls.

Animals↗
PubMed1987

In vitro inhibition of the classical pathway of human complement by polymyxin B.

Polymyxin B was found to be an inhibitor of the classical pathway of the complement system. The main sites of inhibition were the interaction of EAC14 with C2 and EAC142 with C3. It also inhibited EAC1-9 formation from EAC1-3 and C5-9 though slightly less efficiently. It did not inhibit C3/C5 convertase of the alternative pathway or its formation. The inhibition of the classical pathway was reversible since hemolytic activity was almost completely restored after dialysis.

Animals↗
PubMed1987

Reinvestigations into the formation and assay of C3bBbP complexes.

C3bBbP complex formation was studied by an enzyme linked immunosorbent assay (ELISA). Microtitre plates were coated with anti-P to trap the complexes and peroxidase labelled anti-C3 was used to detect them with the help of substrates of peroxidase. Incubation of normal serum pool (NSP) at 37 degrees C in the presence of high concentrations (greater than or equal to 0.5 mmol/l) of Mg2+, usually used in alternative pathway (AP) assay systems, caused the generation of C3bBbP complexes. This generation was not observed when NSP was incubated in the presence of low Mg2+ concentration (less than or equal to 0.2 mmol/l) or EDTA. The concentration of Mg2+ required for maximum complex formation was 2.0 mmol/l under the experimental conditions. Complexes could not be generated in B-depleted serum. Incubation of NSP with endotoxin or CoVF in the presence of 0.2 mmol/l Mg2+ caused the generation of the complexes. The generation was influenced by ionic strength in the incubation mixture. Endotoxin and Mg2+-dependent generation of complexes could not be detected when peroxidase-labelled anti-B was used instead of peroxidase-labelled anti-C3. Serum incubated with 0.2 mmol/l Mg2+ or EDTA apparently detected in vivo formed complexes whereas that incubated with 0.2 mmol/l Mg2+ and endotoxin reflected the complex forming capacity of the serum. The serum of a patient with Raynaud's phenomenon having 45% of normal AP activity did not show increased amounts of preformed complexes but had the ability to generate the complexes to a level of about 45% of that attainable by NSP. These observations suggest that the ELISA used here has the potential of detecting activation as well as the integrity of the AP under carefully controlled conditions.

Complement C3↗
PubMed1987

Psoriasis specific chromosomal proteins, antibodies against them and disease activity.

It has been demonstrated recently that the lymphoid cells of patients with psoriasis have antibodies directed against the psoriasis specific non-histone proteins. A conceptual hypothesis for the role of these antibodies in the pathogenesis of psoriasis presented in this communication, is as follows. Perhaps the psoriasis specific non-histone proteins following phosphorylation bind to histone which keeps psoriasis gene(s) repressed. This may result in the displacement of histone from the DNA. Antibodies against psoriasis specific non-histone proteins may facilitate the displacement of histone. DNA set free, possibly containing psoriasis gene(s), can then be transcribed into RNA causing a shift of the resting pool of keratinocytes in the symptom-free skin of psoriasis patients to the proliferating pool of keratinocytes in the psoriasis lesions.

Antibody Specificity↗
PubMed1987

Immunopotentiation.

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Adjuvants, Immunologic↗
PubMed1986

New methods for the preparation of the cellular intermediate EAC14.

The cellular intermediate EAC14 was successfully prepared by incubating optimally sensitized sheep erythrocytes (EA) with normal serum diluted in complement diluent buffer containing suitable amounts of inhibitors of EAC142 formation from EAC14 and C2, namely polymyxin E and polymyxin B. EAC14 cells could also be prepared by incubating EA with normal serum diluted in Mg2+ free complement diluent buffer in the presence or absence of sucrose. The cellular intermediates prepared by these methods exhibited characteristic EAC142 formation and decay profiles and were found to be suitable for C2 estimations.

Animals↗
PubMed1986

In vitro inhibition of the classical pathway of human complement by a natural microbial product, colistin sulphate.

Colistin sulphate was found to be an inhibitor of the classical pathway of the complement system. The main sites of inhibition were the interaction of EAC14 with C2 and EAC142 with C3. It also inhibited EAC14 formation from EA and C2-deficient serum, EAC1-7 formation from EAC1-3, C5, C6 and C7 and the interaction of EAC1-7 with C8 and C9, though less efficiently. It did not inhibit formation of C3/C5 convertase of the alternative pathway. The inhibition of the classical pathway was reversible since hemolytic activity was completely restored after dialysis.

Animals↗
PubMed1986

Inhibition of complement by a series of substituted 2-aryl-1,3-indandiones: interaction with the fifth component of complement.

A series of substituted 2-aryl-1,3-indandiones were investigated for their ability to inhibit the complement system. Some of them were found to be considerably strong inhibitors. The inhibitory activity was mainly dependent on substitutions at positions 3 and 5 of the phenyl ring. 3,5-dichloro-(8), 3,5-bis(trifluoromethyl)- (7), 3,5-diisopropyl- (3) and 3,5-di-t-butyl- (5) phenylindandiones were the strongest inhibitors of the series. The generation of EAC1-5 cells from EAC1-3 cells and C5 was most strongly inhibited by these compounds although some inhibition of the interaction of EAC1-5 with C6-C9 and EAC1-6 with C7-C9 was also observed. Slight inhibition at other steps of complement activation was also seen but this was not considered to be appreciable. Dialysis of normal serum or purified C5 pre-incubated with compounds 3, 5, 7 and 8 did not cause recovery of the hemolytic activity of normal serum or purified C5. Thus, the main site of inhibition in the complement cascade appeared to be at C5. The total alternative pathway was also inhibited to some extent by these compounds, probably due to their interaction with C5.

Animals↗