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Biomedical subjects

A Kharazmi

Publications and source records attributed to A Kharazmi.

At least 163 records · Page 9Linked to original sources

Opsonic activity of serum in the acute phase of meningitis.

The present study was designed to determine the opsonic activity of serum obtained from meningitis patients in the acute stage of their illness. This study was part of a Danish multicentre prospective study on various aspects of meningitis for a 12-month period. The opsonic activity of serum was determined by a phagocytosis and a chemiluminescence assay using human peripheral blood polymorphonuclear leukocytes. The mean chemiluminescence and phagocytosis indices determined in the sera of 58 patients suffering from various forms of bacterial or non-bacterial meningitis did not differ significantly from that of control sera. Although sera of 4 patients with pneumococcal, 3 with meningococcal, and 1 with streptococcal meningitis exhibited lower opsonic activity than the control sera in the chemiluminescence assay, their values in the phagocytosis assay were similar to control value. It is concluded that serum opsonic activity in meningitis patients is normal and similar to that of healthy individuals.

Acute Disease↗

Effect of Pseudomonas aeruginosa proteases on human leukocyte phagocytosis and bactericidal activity.

The effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (Ela) on neutrophil phagocytosis and bactericidal activity was examined. It was found that both proteases reduced the phagocytic activity of the leukocytes against P. aeruginosa, whereas they had little effect on the phagocytosis of S. aureus. AP and Ela at concentration of up to 250 micrograms per ml (much higher than the levels detectable under in vivo conditions) did not interfere with the bactericidal activity of the leukocytes against both test organisms. Inhibition of phagocytosis by AP and Ela without effect on the bactericidal activity suggests that the P. aeruginosa proteases most probably exert their effect on the cell surface perhaps by proteolytic cleavage of the cell receptors which are necessary for phagocytosis.

Blood Bactericidal Activity↗

Proliferation induced by Plasmodium falciparum antigen and interleukin-2 production by lymphocytes isolated from malaria-immune individuals.

Affinity-purified Plasmodium falciparum soluble antigens (SPAg) isolated from in vitro cultures of the parasite were shown to be relatively free of nonspecific polyclonal activators. To determine the presence of lymphocytes with specificity against SPAg in the peripheral blood of malaria-immune individuals, the proliferative response and the interleukin-2 (IL-2) production of SPAg-activated mononuclear cells (MNCs) from individuals unexposed, sensitized, and immune to malaria were measured. It was found that MNC isolated from malaria-immune individuals proliferated in response to SPAg and that this activation resulted in measurable IL-2 production in 5 of 10 MNC cultures. MNC isolates from most unexposed individuals did not respond to SPAg. To establish which cells responded to SPAg, different subpopulations of MNCs were tested. Only T helper cells were found to respond, and they responded only when cocultured with monocytes. The finding of parasite-specific T helper cells in the blood of malaria-immune individuals and the fact that some of these cells were able to produce IL-2 in vitro support the hypothesis that in malaria the cellular part of the protective immune response is initiated by immune T cells. These cells may activate nonspecific effector cells (i.e., macrophages) that eliminate the parasite.

Adult↗

Elastase from polymorphonuclear leucocytes: a regulatory enzyme in immune complex disease.

In sputa of 21 cystic fibrosis patients suffering from chronic Pseudomonas aeruginosa lung infections, activities of lysosomal proteases released from polymorphonuclear leukocytes (PMN) and immune complexes were quantitatively determined. The results showed that low immune complex values correlated with high protease activities and vice versa. In a longitudinal study fluctuating, reciprocal changes of the parameters were observed. Therefore, the hypothesis was investigated as to whether PMN elastase cleaves immune complexes and regulates inflammation. It was shown that treatment of immune complex-positive sputa with PMN elastase decreased IgG and IgA immune complex values and lead to cleavage of the immunoglobulins in the hinge region. PMN elastase-treated samples were not able to stimulate the oxidative burst of PMN. Cleavage of in vitro built immune complexes did not lead to liberation of bound antigen. Western blot analysis of one sputum sample revealed split products of the IgG heavy chain. The results suggest that PMN elastase splits off the Fc portion of immunoglobulins in immune complexes and thus regulates inflammation by a feedback mechanism leading to cyclic inflammatory states.

Antigen-Antibody Complex↗

Effect of cyclosporin A on human neutrophil and monocyte function.

The effect of various concentrations of cyclosporin A (CyA), ranging from below peak blood levels to 20 times higher than blood levels of human peripheral blood polymorphonuclear and mononuclear leukocytes, was examined. CyA was found to bind to neutrophils with Kd values in the range of 20-50 nM. CyA at clinically obtainable blood level concentrations had no effect on neutrophil and monocyte chemotaxis, neutrophil oxidative burst, monocyte phagocytosis, or neutrophil bactericidal activity. The data on the release of lactoferrin, a secondary granule substance, from activated neutrophils showed that the calcium ionophore A 23187-induced lactoferrin release was inhibited by treatment of cells with 4 microM CyA, whereas release of lactoferrin from zymosan- or phorbol myristate acetate-activated neutrophils was not affected by the same concentration of CyA. This effect could either be due to differences in the degree of cell membrane perturbation by the various activators or to calcium dependence of neutrophil activation. A third possibility may be that CyA acts at some subsequent steps in the release process of neutrophils. It is concluded that CyA does not interfere with important functions of human phagocytes, the cells that play a major role in the defence against invading microorganisms.

Binding Sites↗

In vitro modulation of human neutrophil chemotaxis by cis(Z)- and trans(E)-clopenthixol, and chlorpromazine.

Phenothiazines have been shown to depress several functions of neutrophils, including chemotaxis. A biphasic effect of chlorpromazine (CPZ) and other phenothiazines on human neutrophil chemotaxis has recently been described. We investigated the effect of the stereo-isomers of clopenthizol, a thioxanthene, and of CPZ on human neutrophil chemotaxis. CPZ, at a concentration of 157 microM, and cis(Z)- or trans(E)-clopenthixol, at 105 microM, decreased cell viability. Cis(Z)- and trans(E)-clopenthixol as well as CPZ exerted a biphasic effect on neutrophil chemotaxis with a maximal enhancement of 57%, 92%, and 119%, respectively, and inhibition at higher concentrations. Enhancement of human neutrophil chemotaxis and possibly of the antibacterial activity of these cells by CPZ and the stereo-isomeric compounds of clopenthixol may have clinical implications especially in immunocompromised hosts. The enhancing effect of trans(E)-clopenthixol is of particular importance as this stereo-isomer of clopenthixol exhibits both antimicrobial and antiplasmodial activity but has no antipsychotic or antihypersecretory effect.

Bacterial Infections↗

Polymorphonuclear leucocytes defective in oxidative metabolism inhibit in vitro growth of Plasmodium falciparum. Evidence against an oxygen-dependent mechanism.

This report presents evidence that polymorphonuclear leucocytes (PMN) from chronic granulomatous disease (CGD) patients, who are defective in oxidative metabolism, are capable of inhibiting in vitro multiplication of Plasmodium falciparum. Using a microtitre in vitro inhibition assay, we incubated various numbers of peripheral blood neutrophils from CGD patients and from normal individuals with P. falciparum isolate F32 in the in vitro culture system. Inhibition of parasite growth by neutrophils was determined after 48 h of culture. At PMN to erythrocyte ratio of 1:50 there was an inhibition of parasite growth of 57% by normal neutrophils and 39% to 68% by CGD cells. When the neutrophils were stimulated by phorbol myristate acetate, both cell types enhanced inhibition of parasite growth. These findings indicate that the oxygen-independent systems of human neutrophils are involved in parasite destruction. Constituents of neutrophil granules such as acid hydrolases, lactoferrin, and cationic proteins could be regarded as potential mediators of parasite destruction.

Female↗

Interaction of Pseudomonas aeruginosa alkaline protease and elastase with human polymorphonuclear leukocytes in vitro.

Little is known about the interaction of Pseudomonas aeruginosa extracellular products and human polymorphonuclear leukocytes. The present study was designed to examine the effect of alkaline protease and elastase purified from P. aeruginosa on human neutrophil function. Neutrophil chemotaxis, oxygen consumption, glucose oxidation, superoxide production, and nitro blue tetrazolium reduction were studied. It was found that alkaline protease and elastase at fairly low concentrations (0.05 and 0.0025 micrograms/ml, respectively) inhibited chemotaxis. The inhibitory effect of both enzymes was increased at higher concentrations. The chemotaxis of preincubated and washed cells was also inhibited. Alkaline protease but not elastase inhibited opsonized zymosan-stimulated neutrophil oxygen consumption, whereas neither of the enzymes had any effect on glucose oxidation and nitro blue tetrazolium-reducing activity of stimulated neutrophils. The data on superoxide production ability of the cells indicated that the cells preincubated with enzyme and washed were capable of producing superoxide equal to the amount produced by untreated cells when they were stimulated with phorbol myristate acetate or zymosan. However, when elastase was present in the reaction mixture, the reduction of cytochrome c as a measure of superoxide production was inhibited. Inhibition of neutrophil function, particularly chemotaxis, will have important bearing on the escape of the microorganism from the phagocytic defense system of the host. The role of these products in localized infections and avascular areas such as skin burns, cornea, and, at least initially, in chronic lung colonization in cystic fibrosis patients becomes important.

Chemotaxis, Leukocyte↗

Pseudomonas aeruginosa exoproteases inhibit human neutrophil chemiluminescence.

The present study was designed to examine the effect of Pseudomonas aeruginosa alkaline protease and elastase on human polymorphonuclear leukocyte chemiluminescence. Both a luminol-enhanced and a nonenhanced chemiluminescence system using opsonized zymosan were utilized. It was found that alkaline protease and elastase at concentrations of 25 micrograms/ml strongly inhibited luminol-enhanced myeloperoxidase-mediated chemiluminescence, whereas inhibition of the nonenhanced chemiluminescence response was about 50%. In an attempt to determine the mechanism of inhibition of neutrophil chemiluminescence by these proteases, we examined the effect of various inhibitors of neutrophil oxidative metabolism on chemiluminescence, namely, superoxide dismutase, sodium azide, and catalase. It was shown that the pattern of inhibition of chemiluminescence by alkaline protease and elastase was similar to that of sodium azide, inhibitor of myeloperoxidase. The present study demonstrates that alkaline protease and elastase, extracellular products of P. aeruginosa, are capable of inhibiting myeloperoxidase-mediated chemiluminescence, one of the major antimicrobial systems of polymorphonuclear leukocytes. These findings provide further evidence for the role of P. aeruginosa exoproteases as virulence factors in the pathogenesis of infections caused by this microorganism.

Azides↗

Enhanced inhibition of in vitro multiplication of Plasmodium falciparum by stimulated human polymorphonuclear leucocytes.

The effect of normal human peripheral blood polymorphonuclear leucocytes on in vitro multiplication of Plasmodium falciparum malaria parasites was investigated. It was shown that normal neutrophils were able to phagocytose parasitized erythrocytes and free parasites and thus inhibit in vitro multiplication of the parasite. Stimulation of the neutrophils by phorbol myristate acetate, a potent stimulus of leucocyte oxidative metabolism, resulted in enhanced inhibition of parasite growth. Superoxide dismutase, scavenger of superoxide anion, catalase, inhibitor of hydrogen peroxide, and sodium azide, inhibitor of myeloperoxidase, did not abrogate the inhibitory ability of the neutrophils. The results indicate that polymorphonuclear leucocytes play an important role in the defence against P. falciparum malaria.

Azides↗

Immunological and clinical aspects of kidney disease in endemic typhoid fever in Iran.

Immunological events in the acute, recovery and convalescent stages of typhoid fever were correlated with the occurrence of renal disease in 24 consecutively selected patients. Serum complement levels (C3) were significantly reduced in patients with renal disease during the acute state (p less than 0.01) and increased to normal levels in the recovery phase. IgG and IgM immunoglobulin levels were significantly lower than control values in all three stages (p less than 0.05). While IgA levels were elevated to above control levels in patients with and without renal disease in all three stages, IgA levels were lower in patients with renal disease compared to those without renal involvement in the acute stage (p less than 0.025). The percentage of T cells was increased significantly in all three stages (p less than 0.01). Seven patients showed renal abnormalities. All of them had glomerular disease demonstrated by proteinuria of 1.0 g or greater per 24 h, associated with significant haematuria. Almost all of these patients were glucose-six-phosphate-dehydrogenase (G.6.P.D.) deficient. Serum blood urea nitrogen was elevated in five of these patients who were G.6.P.D. deficient, and two of them developed classical acute tubular necrosis. It appears that renal involvement in typhoid fever commonly occurs as transient glomerular or tubular disease in G.6.P.D. deficient individuals. Glomerular disease is associated with a decrease in serum complement (C3) level in acute stage.

Adolescent↗

Effect of antimalarial drugs on human neutrophil chemotaxis in vitro.

The effect of several antimalarial drugs, commonly used for prophylaxis and therapy of human malaria, on polymorphonuclear leukocyte chemotaxis was studied. A modified, reversible Boyden chamber method was used. Various concentrations of each drug was mixed with neutrophils and incubated in the chambers for 2 1/2 hours. After the incubation period percent inhibition of chemotaxis was determined. It was shown that chloroquine, quinine, proguanil, and tetracycline at concentrations frequently obtained in clinical situations significantly inhibited chemotaxis of neutrophils towards casein. There was a direct correlation between increasing drug concentration and percent inhibition of chemotaxis. Drugs such as pyrimethamine and fansidar at any concentration tested had no effect on chemotaxis.

Antimalarials↗

Evidence for the presence of circulating immune complexes in serum and C3b and C3d on red cells of kala-azar patients.

The presence of immune complexes in serum, and the existence of immunoglobulin and complement on the surface of red blood cells of kala-azar patients was studied. IgG, C3b and C3d were detected on the surface of red cells of some of the patients by a direct anti-globulin test. PEG precipitation and platelet aggregation techniques demonstrated the existence of immune complexes in the sera of all nine patients examined. Both Leishmania antigen and anti-Leishmania antibody were detected in the PEG-precipitated immune complexes.

Antigen-Antibody Complex↗

T and B lymphocytes in alpha-chain disease.

The patients studied were diagnosed as suffering from alpha-chain disease by their clinicopathological features, malabsorption findings, X-ray, and presence of abnormal alpha-chain protein in their serum. The objective of the study was to determine any possible defect of the immune system in such patients. The rosette technique and surface immunofluorescence were used to enumerate the circulating T and B lymphocytes in these patients. They were also skin-tested with tuberculin and given sensitizing doses of dinitrochlorobenzene. Their serum immunoglobulins were also quantitated. It was found that the proportion of circulating B lymphocytes was much higher than normal, whereas that of T lymphocytes was lower than normal. Furthermore, they could not be sensitized to DNCB and their skin test to tuberculin was negative. It was concluded that the disease was a B-cell disease of IgA type, associated with low level of cellular immunity.

B-Lymphocytes↗

Primary upper small-intestinal lymphoma and alpha-chain disease. Report of 10 cases emphasizing pathological aspects.

Ten cases of primary upper small-intestinal lymphoma associated with alpha-chain protein in serum were discovered in a prospective study of the sera of patients with immunoproliferative small-intestinal disease (IPSID). Patients were mostly young males presenting with abdominal pain, weight loss, and diarrhea and showing laboratory evidence of carbohydrate, fat, and vitamin B12 malabsorption and hypoalbuminemia. The more frequently encountered pathologic abnormality was a diffusely nodular jejunal mucosa produced by a plasmacytic infiltrate of variable cell maturity involving a varible depth of small bowel wall with or without involvement of the mesenteric or para-aortic-lymph node complex and, in one instance, the liver. A less frequent picture included circumferential ulcerative and constrictive transmural tumors of the upper small intestine produced by a malignant lymphoma with involvement of abdominal lymph nodes. Small-intestinal surface epithelial abnormalities, a dense mantle of mature plasma cells overlying the lymphoma, a pronounced follicular lymphoid hyperplasia adjacent to and at distances from the lymphoma were other features of note in our IPSID cases associated with alpha-chain protein.

Adolescent↗

Immunological features of kala-azar.

Serum immunoglobulins, complement C3c, percentage of T and B cells, and skin reactivity to Leishmania were studied in ten cases of kala-azar. Immunoglobulin G was increased in a majority of these patients. The C3c level in two out of six patients tested was lower than normal. The percentage of T cells in peripheral blood of nine patients tested was reduced and in seven of these patients the percentage of B cells was elevated. After a full course of anti-kala-azar therapy the percentage of T and B cells remained the same in five patients studied. All the patients showed a negative skin reaction when they were tested with Leishmania antigen.

Adult↗

Immunoperoxidase study in alpha-chain disease.

Peroxidase-antiperoxidase technique was applied to search for the presence of alpha-chain protein in cells of the infiltrate from six cases of alpha-chain disease (one immunoblastic sarcoma and five plasmacytosis cases). Cases of poorly differentiated lymphocytic and Burkitt's type lymphomas, IgA myeloma, and tuberculous enteritis served as controls. Infiltrate cells from alpha-chain disease showed heavy and diffuse staining with anti-alpha-chain and not light-chain antisera. The myeloma reacted with both anti-alpha and anti-kappa antisera. Plasma cells from tuberculous enteritis showed variable staining with anti-heavy- and anti-light-chain antisera, while control lymphomas did not stain at all. We suggest that immunoenzyme histochemistry is a useful tool in demonstrating intracellular alpha-chain protein.

Antibodies, Anti-Idiotypic↗

Alpha heavy-chain disease in southern Iran.

A prospective study of 32 patients with primary upper small intestinal lymphoma in our region revealed 10 cases of alpha heavy-chain disease. Patients were mostly in the second and third decades of life and males predominated. Weight loss, diarrhea, and abdominal pain were the most common complaints and clubbing the most frequent physical findings. Laboratory tests revealed a malabsorption pattern on intestinal x-rays, and malabsorption of xylose, fat, and vitamin B12 was frequently noted. Dense plasmacytic infiltrate of the lamina propria of small bowel was the most frequent pathologic finding while true neoplasm of the lymphoid system (ie, immunoblastic sarcoma) was encountered in 20% of the cases.

Adolescent↗