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PubMed1983

Chemotaxis: basic aspects of methodology, mechanisms and pathology.

This review is an attempt to discuss the basic conceptual tools that are a prerequisite for any clinical study of chemotactic defects. They include familiarity with definitions of common terms and with the merits and drawbacks of the several possible in vivo and in vitro assay methods. Cellular mechanisms involved in locomotion are complex. They include basic requirements for cell metabolism as well as receptor recognition, attachment to surfaces and contraction of the cytoskeleton of the cell. Of the many chemotactic factors reported, few are well characterized and universally agreed upon. Similarly, with the use of more stringent criteria, a number of clinical defects of chemotaxis have proven transitory or even artifactual.

Adult↗
PubMed1985

Generalised glucosephosphate isomerase (GPI) deficiency causing haemolytic anaemia, neuromuscular symptoms and impairment of granulocytic function: a new syndrome due to a new stable GPI variant with diminished specific activity (GPI Homburg).

A new glucosephosphate isomerase (GPI) variant is described which is characterised by very low specific activity in erythrocytes, granulocytes and muscle tissue, nearly normal stability, normal kinetic properties and a decreased electrophoretic mobility. The propositus suffers from a complex syndrome involving erythrocytes (congenital haemolytic anaemia), granulocytes (decreased production of superoxide anion and reduced bactericidal activity in vitro) and the neuromuscular system (myopathy, mental retardation). It is suggested that the clinical syndrome results from generalised GPI deficiency due to a decreased specific activity of the variant enzyme, which cannot be compensated by an increase of de-novo synthesis of GPI protein even in cells exhibiting active protein synthesis such as granulocytes and muscle cells.

Adolescent↗
PubMed1975

[Defective polymorphonuclear leukocyte function in chronic granulomatous muco-cutaneous candidiasis (author's transl)].

Chronic granulomatous muco-cutaneous candidiasis is reported in a 12-year-old boy who died of pulmonal cryptococcosis. Chemotactic and phagocytic functions of the neutrophilic polymorphonuclear leukocytes were deficient while the cell mediated immunity was not disturbed and no decrease of immunoglobulins and complement factors--especially C3 and C5--was found in the serum. The possibility is considered that the disturbance of lymphocyte mediated immune response is the normal, but not only fundamental aetiological factor of chronic muco-cutaneous candidiasis.

Animals↗
PubMed1984

Deficiency in C3b receptors on neutrophils of patients with chronic granulomatous disease and hyperimmunoglobulin-E recurrent infection (Job's) syndrome.

C3b receptor (CR1) expression by neutrophils (PMNs) and erythrocytes (Es) from patients with chronic granulomatous disease (CGD) or with hyper-IgE, frequent infection (Job's) syndrome was compared with that of control subjects. The control subjects consisted of one group of patients with infections and a second group of normal, healthy individuals. Three quantitative assays were used: rosette formation with C3b-coated cellular intermediates (EAC43b), binding of radiolabeled monoclonal anti-CR1 ([125I]anti-CR1) to PMN surfaces, and binding of the antibody to nonidet P-40 (NP-40) extracts of PMNs and Es in an immunoradiometric assay. Rosette formation by the PMNs of five male CGD patients was about 50% of that of paired normal control subjects, whereas the rosette formation of three female CGD patients was similar to that of the control subjects. Surface binding of [125I]anti-CR1 to PMNs of 10 CGD patients was about half that of the normal subjects (mean percent binding was 2.33% for the CGD patients vs. 3.86% for the normal subjects, giving a difference of -1.53 +/- 0.22%, P less than 0.001 by the paired-sample t test). The degree of PMN binding was similarly low for both the male and the female CGD patients. Conversely, the binding of anti-CR1 to the PMNs of 11 infected control patients appeared to be similar to that of the normal subjects (4.51% for the patient vs. 4.21% for the paired normal subjects). The infected control group originally included four Job's syndrome patients, and when this subgroup was analyzed separately, their PMNs were shown to bind significantly less anti-CR1 than did the PMNs of the normal subjects (P less than 0.01 by the paired-sample t test). In contrast, the other infected control patients showed higher-than-normal levels of anti-CR1 binding (P less than 0.05). When compared to that of the normal subjects, the total CR1 quantitated in PMN extracts was also lower than normal in CGD patients (P less than 0.01 and in the PMN extracts of eight Job's syndrome patients tested (P less than 0.01). The PMNs of the other infected control subjects were not significantly different from those of the normal subjects in total CR1 expression. Extracts of Es from Job's syndrome patients also had fewer than normal CR1 (P less than 0.02). On the other hand, CR1 levels in E extracts from the CGD patients and the other control patients were similar to those in the normal control subjects. Quantitations of C3, C4, and factor B were normal in CGD.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Antibody Complex↗
PubMed2006

Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2.

Blau syndrome (BS) is a rare familial granulomatous disease manifested by uveitis, arthritis and skin rash. BS has recently been found to be associated with a distinctive mutation in NOD2, which encodes an intracellular toll-like receptor. We have compared host cell interaction with bacterial challenge in U937 cells expressing wild type human NOD2 (NOD2(wt)), mutant NOD2 (NOD2(Blau)), or a vector control (VC). The cells were incubated with Salmonella typhimurium. Intracellular uptake was assessed by harvesting the cells at different time points following invasion and quantitating the CFU, recovered after gentamicin treatment to kill extracellular organisms. Expression of TNF-alpha, TLR2 and TLR4 was determined by semi-quantitative RT-PCR under resting conditions and after stimulation by bacteria. Invasion of target cells with S. typhimurium was diminished in the presence of NOD2(Blau). Expression of TNF-alpha mRNA was enhanced following bacterial invasion in all cell lines but NOD2(Blau) was associated with a more rapid decline in TNF-alpha expression. Kinetics of intracellular clearance of bacteria indicated a relative defect in NOD2(Blau) compared to controls. This clearance defect may be related to the lack of sustained TNF-alpha seen in the early stages. These events were not related to differential TLR2 or TLR4 expression since there were no significant differences seen between the cell lines after bacterial stimulation. Our findings indicate that the NOD2 mutation associated with this syndrome alters host:microbial interaction, and this may have relevance to triggering factors in the ocular and joint inflammation seen in BS.

Arthritis↗
PubMed1976

Fate of the retained rectum after subtotal colectomy for inflammatory disease of the colon.

Of forty-nine consecutive patients who underwent subtotal colectomy for inflammatory disease of the colon, 73.5 per cent required subsequent combined abdominoperineal resection of the retained rectum and only two patients had successful ileoproctostomy. For the patient whose rectum is substantially diseased along with the rest of the colon, one-stage total proctocolectomy is the preferred operation.

Adolescent↗
PubMed1976

Lack of cytochalasin E-induced superoxide release by polymorphonuclear leucocytes of patients with chronic granulomatous disease: a new diagnostic test.

Reduction of exogenous cytochrome c was induced by the treatment of human polymorphonuclear leucocytes with cytochalasin E. The reduction was completely inhibited by superoxide, dismutase, indicating that superoxide anions were released from the cells. The leucocytes from two patients with chronic granulomatous disease did not show the release reaction that should have been brought on by the treatment. The cytochalasin-induced reduction of exogenous cytochrome c by polymorphonuclear leucocytes is so specific and sensitive that it seems to be useful for diagnosis of chronic granulomatous disease.

Adult↗
PubMed1978

Cyanide-insensitive respiration of phagocytes in oxygen-treated whole blood.

Cyanide-insensitive respiration of phagocytes has been assayed polarographically in less than 0.5 ml of oxygenated venous blood. Cell separation procedures are avoided by use of whole blood as assay sample. The method is simple and gives quantitative results. The values obtained faithfully reflect in vivo capacity of phagocytes. Blood from boys with chronic granulomatous disease showed no burst of oxygen consumption during phagocytosis. Blood from their mothers showed about one-third activity of normal blood, indicating their carrier status.

Cyanides↗
PubMed1988

Cryptococcosis of the colon resembling Crohn's disease in a patient with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome.

A 29-yr-old woman presenting with granulomatous colitis and a chronic perirectal abscess was found to have localized cryptococcosis associated with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome. Similarity to previous cases of esophageal cryptococcosis and ileocecal histoplasmosis suggests an association between the hyperimmunoglobulinemia E-recurrent infection syndrome and localized fungal infections of the alimentary tract. To our knowledge, this is the first well-documented case of cryptococcosis confined to the colon and perirectal tissues.

Adult↗