PubMed HealthSearch

Biomedical subjects

J Hed

Publications and source records attributed to J Hed.

At least 19 recordsLinked to original sources

Lability in complement receptor mobilization of granulocytes in patients with bronchial hyperreactivity.

The recruitment of activated granulocytes to bronchial mucosa seems to be involved in the prolonged inflammatory response observed in asthma and probably associated with bronchial hyperresponsiveness. We studied the patients with bronchial hyperresponsiveness with respect to the expression of complement receptor type 1 (CR1), its variability and readiness to become mobilized on peripheral granulocytes from patients with bronchial hyperresponsiveness. CR1 expression and its hourly variation was significantly (P less than 0.02, P less than 0.01 respectively) higher in the patient group compared with the control group. In addition the ability to mobilize CR1 spontaneously at +37 degrees C correlated to the variation of CR1 expression that occurred during a 4 hr period. These findings indicate that granulocytes from patients with bronchial hyperresponsiveness have a higher degree of variation in CR1 expression that correlates to their ability to mobilize CR1 and may reflect a more pronounced lability.

Adolescent

Autoantibodies to leucocyte antigens in hydralazine-associated nephritis.

Clinical and laboratory findings and drug history were studied in 17 patients with suspected hydralazine-associated nephritis, five of whom only had renal disease, while twelve also had extrarenal manifestations. Renal biopsies revealed extracapillary proliferative or focal segmental proliferative glomerulonephritis in 10 patients, and tubulo-interstitial nephritis in five patients. Antinuclear antibody (ANA) was found in 16 patients, but none of the 14 patients tested had antibodies to DNA. Tests for antibodies to myeloperoxidase (anti-MPO) and antibodies to neutrophil cytoplasm antigen (ANCA) were performed by ELISA. Twelve of the 14 patients tested had anti-MPO; five of these 14 patients had ANCA, while one had borderline levels. These findings suggest that hydralazine facilitates the induction of a systemic disease with multiple autoantibody production.

Antibodies, Antinuclear

Increased expression of adhesion proteins (MAC-1) and altered metabolic response in human leukocytes exposed to surfactant in vitro.

In this study the modulatory effects of a well-defined surfactant preparation on blood leukocytes were investigated. The expression of the cell surface receptor MAC-1 was analyzed by flow cytofluorometry, and the metabolic response was measured by a chemiluminescence technique. An increase (p less than 0.05) in the MAC-1 receptor expression was observed in the granulocytes but not in the monocytes. There was a decrease in the metabolic response of the leukocytes after stimulation with phorbol myristate acetate (PMA) and a delay (p less than 0.01 for both) in the peak activity. Formyl-methionyl-leucyl-phenylalanine (fMLP) caused an increased peak (p less than 0.01). Thus, the surfactant preparation had a modulatory effect on blood leukocytes with regard to the expression of the cell surface receptor MAC-1 and the metabolic response.

Adolescent

Mobilization of an intracellular glycoprotein (Mac-1) on monocytes and granulocytes during hemodialysis.

We studied the upregulation of the intracellular glycoprotein Mac-1 (CD11b/CD18, CR3) on monocytes and granulocytes during 36 bicarbonate hemodialyses in 12 patients who were randomly treated with Cuprophan (Cu), Hemophan (He) or Polysulfone (PS; low-flux) membranes. The degree of mobilization of this adhesion protein was related to changes in granulocyte and monocyte count, generation of C3a and production of interleukin-1 beta in plasma. Mac-1 expression on granulocytes was significantly higher after 5 and 15 min of Cu hemodialysis as compared to He or PS dialyses (p < 0.001) and correlated to changes in granulocyte count at 15 min (r = 0.62 and r = 0.76, p < 0.001). No differences in early Mac-1 mobilization on circulating monocytes was observed despite a decrease in cell count. Mac-1 expression on monocytes and granulocytes in the venous blood line at 180 min of treatment was significantly higher during Cu dialysis as compared to He and PS dialyses (p < 0.02 and p < 0.001, respectively). Early generation of C3a was higher in patients on Cu dialysis than in He or PS dialysis (p < 0.001) and correlated both to granulocytopenia (r = 0.45, p < 0.01) and to the subsequent increase in Mac-1 expression on granulocytes (r = 0.63, p < 0.001). An early increase in Mac-1 expression on monocytes was accompanied by an increase in plasma interleukin-1 beta later during dialysis (p < 0.05). Studies of Mac-1 expression during hemodialysis increased the sensitivity of biocompatibility measurements and correlated better than complement generation to changes in granulocyte count as it mediates adhesion to endothelial cells.

Adult

Dialysis granulocytopenia is preceded by an increased surface expression of the adhesion-promoting glucoprotein Mac-1.

We studied the expression of Mac-1 on granulocytes (flow cytometry) from 9 patients (27 examinations) during hemodialysis with cuprophane membranes (CuM). Samples were drawn before dialysis and from the arterial and venous lines at 5, 15 and 180 min. Granulocytopenia was most pronounced after 15 min of treatment. Mac-1 expression on granulocytes increased during dialysis, and a pronounced enhancement occurred across the dialyzer. Mac-1 expression on granulocytes increased 116% across the dialyzer at 5 min, and the degree of Mac-1 mobilization at 5 min correlated with the degree of subsequent granulocytopenia at 15 min. In in vitro experiments, granulocytes from healthy blood donors were incubated with plasma drawn from the arterial and venous lines at 5 min. Plasma drawn from the venous line at 5 min had a greater ability to mobilize Mac-1 than plasma from the arterial line (p less than 0.002). This difference correlated with the degree of granulocytopenia at 15 min (r = 0.76, p = 0.01). Pieces of a washed CuM were incubated in normal human serum (NHS) preparations for different times. Inactivation of the alternative pathway of complement activation (NHS-50 degrees) did not alter the generation of Mac-1-mobilizating capacity compared to NHS. In contrast, inactivation of the classical pathway (NHS-EGTA) decreased the early but not the late generation of Mac-1-mobilizating capacity. Our results indicate that the early mobilization and not the absolute expression of Mac-1 correlates with granulocytopenia, and that sera in vitro attain Mac-1-mobilizating capacity more rapidly when the classical pathway of complement activation is intact.

Aged

Smoking cessation rapidly reduces cell recovery in bronchoalveolar lavage fluid, while alveolar macrophage fluorescence remains high.

Bronchoalveolar lavage (BAL) was performed in smokers (22.6 +/- 7.8 pack-years) before (n = 18) and 1 (n = 14), 3 (n = 13), 6 (n = 11), 9 (n = 9), and 15 (n = 8) months after smoking cessation. The recovery of the BAL fluid increased after smoking cessation (p less than 0.05). The total number of cells and the cell concentration were significantly lower already at one month (p less than 0.05 and p less than 0.01, respectively), and this decline was more pronounced at the following lavages. By using flow cytofluorometry, alveolar macrophage (AM) fluorescence was quantified, since it is known that AMs lavaged from smokers have an increased fluorescence, due to interaction with fluorescent substances in the inhaled smoke. Not until six months after smoking cessation was a significant (p less than 0.05) decrease in AMs fluorescence noted. At 15 months, the fluorescence was still increased, with great individual variations, compared with AMs from nonsmokers. The decline in fluorescence of AMs after smoking cessation was negatively correlated to the previous cigarette consumption. The absence of new, low fluorescent cells in the BAL fluid, despite a slow, but significant decrease in the fluorescence intensity of the whole cell population, suggests that the fluorescent material is redistributed from older AMs to newly recruited cells. These substances can thus remain in the alveolar space for a longer time than the estimated life span of the AMs.

Adult

Endocytosis of cigarette-smoke condensate by rabbit alveolar macrophages in vitro measured as fluorescence intensity.

It has previously been shown that alveolar macrophages (AMs) from smokers have increased fluorescence compared to AMs from nonsmokers. In the present investigation, AMs lavaged from rabbits were exposed to a cigarette-smoke condensate (CSC) in order to study its influence on the fluorescence of AMs. Flow cytofluorometry was used. Alveolar cells exposed to 0.01% of CSC showed a fluorescence which increased with higher concentrations of the CSC. Incubation with CSC for 5 min was enough to give a significant rise (p less than 0.001) in cell fluorescence compared to controls. After incubating fluorescent cells with untreated non-fluorescent AMs, fluorescent material was distributed to the non-fluorescent AMs within 30 min. Further more, fluorescence decreased when exposed cells were cultured in CSC-free medium. When incubating CSC with blood leucocytes, an almost threefold increase in fluorescence was observed among the phagocytic cells at 37 degrees C compared to 4 degrees C, whereas the fluorescence in the non-phagocytic cell population only showed a minor enhancement. Endocytosis of fluorescent material in CSC can explain the strong fluorescence seen in AMs from smokers. Exocytosis and re-endocytosis of the material by new AMs may explain the slow decline in the fluorescence of AMs observed after cessation of smoking.

Animals

High prevalence of celiac disease in healthy adults revealed by antigliadin antibodies.

Sera from 1866 healthy blood donors and from 40 untreated adults with celiac disease were analyzed using a micro-ELISA assay. Blood donors with IgA antigliadin activity greater than 40 units corresponding to the 96.8th percentile and IgG antigliadin activity greater than 20 units corresponding to the 91.3rd percentile were selected for further investigation and jejunal biopsy. Seven of 49 blood donors with high IgA antigliadin activity showed mucosal lesions typical for celiac disease. None of the donors with high IgG antigliadin activity (35 subjects) but without high IgA activity had such mucosal lesions. A prevalence of celiac disease of at least 1/256 was observed in the donor group. There were significant age-group differences in IgA antigliadin activity. In the present study, a high IgA antigliadin activity had a positive predictive value between 18% and 25% in individuals without symptoms indicative of celiac disease depending on the way the cut-off points were chosen. In contrast, the positive predictive value of high IgG antigliadin activity alone was estimated to be 0%.

Adolescent

Quenching of intracellular autofluorescence in alveolar macrophages permits analysis of fluorochrome labelled surface antigens by flow cytofluorometry.

We report a new technique in which the autofluorescence of alveolar macrophages from smokers is quenched by crystal violet. This technique permits immunostaining of surface antigens of these cells and enables the stained cells to be analysed by flow cytofluorometry. The variable solubility of crystal violet makes it important to characterize the crystal violet solution by its quenching properties and not rely on the assumed concentration of dissolved dye. High concentrations of crystal violet lowered the number of cells and gave a decreased amount of surface antigen (CD11b). However, a lower concentration of crystal violet could be used if the cells were fixed with paraformaldehyde (4%) and the membranes were permeabilized with n-octyl-beta-D-glucopyranoside (0.6%). Using a phagocytic model with FITC-conjugated particles we were able to show that this treatment gave an efficient permeabilization of phagolysosomal membranes.

Antigens, Surface

A flow cytometric method to measure the stimulated mobilization and the intracellular pool of the adhesion promoting glucoprotein Mac-1.

The receptor for complement factor C3bi (Mac-1 or CR3) belongs to a complex of leukocyte surface glucoproteins (CD11/CD18) that are essential for chemotaxis and adhesion of human polymorphonuclear leukocytes (PMN). Granulocytes can increase their surface expression of Mac-1 upon stimulation and it is proposed that this depends on a rapid mobilization of an intracellular pool of Mac-1. In the present study we describe a cell membrane permeabilization method that enables the detection of the intracellular pool of Mac-1 in granulocytes by flow cytometry. The method is based on the use of the non-ionic detergent n-octyl-beta-D-glucopyranoside (OG) to permeabilize the cell membranes of paraformaldehyde-prefixed leukocytes. It is shown that fMLP (5 x 10(-7) M)-treated cells expose 85% of the total detectable amount of Mac-1 molecules on the surfaces. The method makes it possible to measure the total detectable pool, the efficiency of Mac-1 mobilization and the in vivo expression of the receptor. This could be of value when evaluating the role of adhesion proteins in the inflammatory response.

Adolescent

Dust exposure in coeliac disease: a case-referent study.

Case series of coeliac disease show that chronic allergic alveolitis (farmers' lung) and fever reactions due to exposure to organic dust (organic dust toxic syndrome) commonly occur among subjects with coeliac disease and dermatitis herpetiformis, these being related disorders. In this case-referent study 105 cases of coeliac disease and dermatitis herpetiformis were compared with 237 referents from the general population by means of a mail inquiry regarding exposure to various environmental factors. Increased odds ratios were obtained with exposure to various farm animals and more clearly for cotton dust, although numbers were few. Animal husbandry in Sweden invariably means heavy exposure to organic dust. The fact that comparatively few persons reported dust exposure may be of doubtful validity in view of the high frequency of exposure to farm animals reported by the cases.

Adult

Antibody responses to hepatitis C virus and its modes of transmission in dialysis patients.

Five of 72 patients dialysed at the same dialysis unit developed elevated alanine aminotranspherase (ALT) levels attributed to acute non-A, non-B hepatitis (NANBH). Histopathologic findings consistent with NANBH were present in four of them. Serological screening for antibodies to hepatitis C virus (anti-HCV) was performed in all 72 cases. Three of the patients with NANBH and 2 of the other 67 patients had positive tests. Low and transient levels of anti-HCV were noted in 2 patients with NANBH in spite of chronic hepatitis. Only 1 of 5 patients with NANBH was known to have had blood transfusions indicating other, as yet undefined, modes of transmission of HCV for the others. Although antibody responses to HCV might be transient or low, testing for anti-HCV should be considered in dialysis populations.

Alanine Transaminase

Raised IgG and IgM in "epidemic" IDDM suggest that infections are responsible for the seasonality of type I diabetes.

Serum levels of immunoglobulins G, A and M were quantitatively measured at diagnosis and at regular intervals for four years in 92 type I (insulin-dependent) diabetes patients. The patients were 0.8-15.99 years of age at diagnosis. Thirty-six of them got diabetes during periods of high incidence (the "epidemic" group) and 56 of them were diagnosed during periods of seemingly low incidence (the non-"epidemic" patients). Fifty percent (18/36) of the "epidemic" group had infections less than two months preceding diagnosis as compared to 29% (16/56) (p less than 0.01) of the non-"epidemic" patients. At diagnosis immunoglobulins G, and M in the "epidemic" group were 11.28 +/- 2.0 and 1.97 +/- 0.77 as compared to 9.9 +/- 2.3 (p less than 0.01) and 1.31 +/- 0.58 (p less than 0.001) respectively in the non-"epidemic" patients. The same highly significant differences were observed when mean values of IgG and IgM were compared between children who had infections less than two months before diagnosis and those without preceding infections. Except for slightly higher (p less than 0.12) total (OKT3) T-lymphocytes and higher (p less than 0.03) B-lymphocytes at diagnosis in the "epidemic" group, there were no significant differences in quantitative T- and B-lymphocyte subpopulations between various groups. 6.3% (2/32) of the patients who had preceding infections had HLA-DR3/non-DR4 genotypes as compared to 30.6% (15/49); p less than 0.001, of those patients without preceding infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The inhibition of CR1 mobilization of human granulocytes by the presence of erythrocytes. A possible mechanism for intravascular regulation of granulocyte modulation.

In this study we show a spontaneous mobilization at 37 degrees of the complement receptor for C3b (CR1) of granulocytes prepared by a method in which erythrocytes were removed by specific lysis, as well as a method where granulocytes were prepared by dextran sedimentation at low temperature without using centrifugation. This increase of CR1-expression was not obtained when erythrocytes were present during the incubation. This inhibitory effect of erythrocytes was maximal at an erythrocyte:granulocyte ratio of 600:1 or more and was not caused by interference with the fluorescence of the immunoassay. EDTA plasma had no inhibitory effect on CR1 mobilization, indicating that the phenomenon was not due to plasma proteins, nor the used anti-coagulant. An increased CR1 mobilization was, however, obtained in the presence of erythrocytes if the granulocytes were simultaneously exposed to the chemotactic stimulus formyl-methionyl-leucyl-phenylalanine (FMLP) at the concentration 10(-9) M or more. However, to obtain a CR1 expression comparable to systems without erythrocytes, a 10-fold higher concentration of FMLP was needed. These results suggest that the inhibitory effect of erythrocytes on the spontaneous receptor mobilization of granulocytes could be a mechanism to keep the complement receptors and other surface structures within the cells while circulating in the blood, to be expressed at the cellular surface only by the appropriate signal, such as propagated by soluble mediators from an inflammatory focus.

Adolescent

The effect of maternal avoidance of eggs, cow's milk, and fish during lactation on the development of IgE, IgG, and IgA antibodies in infants.

Serum levels of IgE, IgE antibodies to egg white (EW) and cow's milk (CM), IgG, and IgA antibodies to ovalbumin (OA) and beta-lactoglobulin (BLG) were measured in a group of 115 infants with a family history of atopy/allergy at birth and at 3, 6, 9, 12, and 18 months of age. The mothers of 65 infants avoided eggs, CM, and fish during the first 3 months of lactation (maternal antigen avoidance diet, D group), whereas the remaining 50 mothers had no diet restrictions (no maternal antigen avoidance diet, ND group). CM was introduced after 6 months of age and EW after 9 months. The only statistically significant difference between the D and ND group infants was a lower rate of specimens with IgE antibodies to EW and/or CM in the infants at 3 months of age (p = 0.008). IgE antibodies to EW and/or CM appeared in 62 infants during the study period and often during complete breast-feeding. In 40 of the infants, IgE antibodies appeared before the introduction of EW and CM into the diet. The IgE concentrations of the D and the ND group infants were similar. Cord-blood IgE was a poor predictor of atopy/allergy; for example, only seven of 103 infants with double heredity for atopy/allergy had values above the 90th percentile of our normal reference. The concentrations of IgG antibodies to OA and BLG were similar in the two groups. The levels decreased significantly (p less than 0.001) from birth to 6 months of age, indicating a passive placental transfer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Different cell surface and phagocytic properties in mononuclear phagocytes from blood and alveoli. A comparative study of blood monocytes and alveolar macrophages from human nonsmokers using flow cytofluorometry.

Flow cytofluorometry was used to compare blood monocytes (BMs) and alveolar macrophages (AMs) from the same nonsmoking subject (n = 13). Autofluorescence was quantified, cell surface markers (HLA-DR, CR3) were detected by monoclonal antibodies, and phagocytic ability was determined using C3b-coated yeast particles. AMs expressed more HLA-DR (p less than 0.001) and CR3 (p less than 0.01) on their surfaces than did BMs. The phagocytic capacity was enhanced in AMs compared to BMs (p less than 0.001) and the cells showed an increased autofluorescence (p less than 0.001) in the alveoli compared to blood. The findings suggest that the mononuclear phagocyte is activated when it migrates from blood to alveoli in order to adapt to the milieu in the alveolar space.

Adult