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Biomedical subjects

R R Kretschmer

Publications and source records attributed to R R Kretschmer.

At least 37 records · Page 2Linked to original sources

[Monocyte locomotion inhibiting factor (MLIF) produced by E. histolytica induces an increase of cAMP in human monocytes].

The supernatant fluid of axenically grown E. histolytica contains a factor (MLIF) which inhibits the locomotion of human monocytes (including chemotaxis) without affecting that of human polymorphonuclear leucocytes. Locomotion, like other cellular functions, is modulated by changes in intracellular cAMP and cGMP. The consensus--with some exceptions--is that while rises in cGMP accompany locomotion, an increase in cAMP (without a concomitant fall in -cGMP) occurs with inhibition of cellular movement. We measured by radioimmunoassay the cAMP concentration of human monocytes exposed to inhibitory concentrations of MLIF. A significant (p less than 0.005) rise in monocyte cAMP was found, comparable to that observed with the use of forskolin, a well known cAMP stimulator. The control studies using plain axenic medium, not only failed to reveal any rise in cAMP but disclosed a small, yet not significant drop in intracellular cAMP. These results suggest that MLIF (like other locomotion inhibitors, i.e. prostaglandins E1, A1 and isoproterenol) produces a significant increase in intracellular monocyte cAMP. This modification in intracellular signals may contribute to the inhibition in monocyte locomotion, an event during which an increase in pericentriolar microtubules has also been observed.

Animals↗

[HLA antigens, complement types, and amebic liver abscess in Mexican mestizos].

The association between parasitic diseases, and antigens of the major histocompatibility complex in man (HLA) has been poorly studied. The only study of the association between the HLA system and amebic abscess of the liver was performed by our group, and revealed a significant increase in HLA-BI6 and HLA-DR3 in patients with amebic abscess of the liver. The present study covered a larger number of patients and controls (110 of each) and it confirmed the association with HLA-DR3, it failed to confirm the association with HLA-BI6.

Adult↗

Destruction of normal human eosinophils by Entamoeba histolytica.

We evaluated the in-vitro interaction of normal human eosinophil leucocytes and a virulent strain of Entamoeba histolytica (HM1-IMSS) in the presence of immune serum. At a 10:1 (eosinophil:amoeba) ratio a significant time-dependent destruction of eosinophils was found from the first hour onward, and a similar, albeit weaker, cytopathic effect was found in the 200:1 ratio mixtures, with some delay in the microscopic evidence of such effect. Results were unaffected by serum factors, and amoebae emerged virtually unharmed throughout these experiments, again regardless of the presence of serum factors. These results indicate that, as with neutrophil leucocytes, virulent E. histolytica is capable of destroying normal human eosinophils in vitro.

Adult↗

Defective polymorphonuclear chemotaxis in patients with Turner's syndrome (45,X).

Polymorphonuclear leucocytes from patients with full Turner's syndrome (45,X) revealed a significantly weaker chemotactic response towards zymosan-activated serum than normal female and male controls. Random mobility and chemokinetic responses of polymorphonuclear leucocytes were normal, and so were all locomotive responses of mononuclear phagocytes in patients with Turner's syndrome. A subclinical polymorphonuclear leucocyte chemotactic defect is suggested by these results, and a possible regulatory effect by a gene(s) in chromosome X (and Y) that must be present in a full double dose to preserve this function can be proposed. Control of polymorphonuclear leucocyte chemotaxis may represent yet another exception to the general rule of X-inactivation.

Adolescent↗

HLA antigens associated to amoebic abscess of the liver in Mexican mestizos.

Worldwide prevalence of amoebiasis is estimated at 4 x 10(8) cases/year, yet only one of about 300 individuals harbouring Entamoeba histolytica suffers tissue invasion and these cases are mostly concentrated in certain areas of Asia, Africa and Latin America. Patients with amoebic abscess of the liver (AAL) represent only a small fraction of that. These contrasting figures have been tentatively explained on the one hand through variations in sex, immunocompetence, nutritional and other socioeconomic features of the host, and on the other hand through differences in parasite virulence. In order to explore a possible association between the major histocompatibility complex (MHC) and AAL susceptibility, we studied the HLA profile in 31 Mexican mestizos with AAL and compared it to race and socioeconomically matched controls. Mexican mestizo patients with AAL revealed a significant increase in HLA-Bw16 and HLA-DR3 which could suggest an HLA-related susceptibility to liver invasion by E. histolytica.

Abscess↗

Ultrastructural changes associated with the inhibition of monocyte chemotaxis caused by products of axenically grown Entamoeba histolytica.

The supernatant fluid of axenically grown Entamoeba histolytica-HM1 significantly modifies the ultrastructural features associated with monocyte chemotaxis as assayed in Boyden chambers. This morphological evidence supports the existence of a factor, monocyte locomotion inhibitory factor (MLIF), produced by E. histolytica that inhibits the in vitro locomotion of human monocytes. None of the leucocyte-locomotion modifying drugs included in this study (i.e., cytochalasin-B, colchicine, vinblastine, and hydrocortisone) caused changes totally comparable with those induced by MLIF. The most striking feature was the increase of centriole-associated microtubules induced by MLIF and by cytochalasin-B. MLIF may inhibit monocyte locomotion by directly inducing excessive microtubule assembly, although a direct, if somewhat weak effect upon microfilaments cannot be excluded. The increase in microtubules could then represent a perhaps futile attempt of the microtubule organizing center to overcome the locomotion blockade that has occurred elsewhere in the cell. If active in vivo, MLIF may contribute to the paucity of inflammation in the advanced stages of invasive amebiasis, and consequently to the lack of scar tissue formation upon recovery from such lesions, as monocytes constitute an essential link to the healing process.

Chemotaxis, Leukocyte↗

Increased leucocyte histamine release by Entamoeba histolytica antigen in patients with amoebic abscess of the liver.

Leucocytes (basophils) from non-atopic adult subjects living in an area highly endemic with Entamoeba histolytica release histamine in a dose-dependent fashion upon in vitro exposure to an antigen of axenically grown E. histolytica (histolyticin). Leucocytes of patients with acute amoebic liver abscess were significantly more sensitive to this antigen than leucocytes of control subjects, including patients that had recovered from amoebic liver abscess. By comparison Concanavalin-A induced histamine release found in patients with amoebic liver abscess and healthy controls suggest an immunological mechanism for histolyticin induced in vitro histamine release. This is also suggested by the inability of histolyticin to release histamine from leucocytes of healthy newborn infants and the significant fall in sensitivity to histolyticin following incubation of leucocytes in acid pH. Histamine and other mediators may contribute locally to the early intense inflammatory reaction observed in tissue invasion by E. histolytica.

Adolescent↗

HLA-B27 and ankylosing spondylitis in the Mexican Mestizo population.

Two previous surveys of ankylosing spondylitis (AS) in Mexican Mestizos found HLA-B27 frequencies of 68.6% and 78% and a relative risk (RR) of 37.05 and 120.88, respectively. We examined an additional group of Mexican Mestizos with AS and found an HLA-B27 frequency of 80.77% and a RR of 99.24. Our results are statistically comparable to the previous studies, and they suggest that the Mexican Mestizo is similar to the Spaniard in regards to AS and HLA-B27 association.

Female↗

Defective monocyte chemotaxis in children with Down's syndrome.

Under-agarose random migration, chemokinesis and chemotaxis of monocytes from 36 patients with Down's syndrome were compared to those of monocytes from 42 healthy, age-matched control children. Random migration of monocytes from patients with Down's syndrome was comparable to that of controls. In contrast, chemotaxis of monocytes from patients with Down's syndrome was significantly decreased (P less than 0.001) when compared to that of controls, even though chemokinesis was significantly increased (P less than 0.001). Age, sex, and physical development of patients with Down's syndrome or of control children included in this study had no apparent effect upon monocyte mobility.

Chemotaxis, Leukocyte↗

An enzyme-linked immunosorbent assay (ELISA) for human IgG antibody to the type Ia polysaccharide of group B streptococcus.

An ELISA was developed to measure human IgG antibody to the native polysaccharide antigen of GBS serotype Ia. Because the polysaccharide binds poorly to polyvinyl chloride, its adherence was enhanced by activation with cyanogen bromide and coupling to HSA in a molar ratio of polysaccharide to albumin of 1:4.5. There was minimal loss of sialic acid during coupling, and the coupled antigen showed identity with uncoupled native antigen by Ouchterlony analysis. OD values obtained by ELISA showed a log-linear relation to concentration of specific antibody in whole and affinity-chromatographed human sera measured by quantitative precipitation over a range of 0.25 to 3.5 microgram/ml. In replicate ELISA experiments using serially diluted human serum, dilutions with antibody content as low as 0.016 microgram/ml could be reliably differentiated from PBS or agammaglobulinemic serum. The concentration of antibody in 98 selected human sera measured by ELISA correlated well (r = 0.89, p less than 0.001) with results obtained by indirect IF assay. This quantitative ELISA for GBS antibody is rapid, convenient, economical, and suitable for routine use.

Enzyme-Linked Immunosorbent Assay↗

HLA profile of the Mexican Mestizo population.

The HLA-A, B and C profile of 665 Mexican Mestizos was studied by microcytotoxicity testing for 30 HLA specificities. Antigen, gene and haplotype frequencies were calculated, and results were compared to those of the three other series of HLA profiles in Mexican Mestizos available in the literature: one from Mexico-City, one from Los Angeles, California, USA, and a recent one from San Antonio, Texas, USA. Comparing the antigen frequencies of our series with those of the other study from Mexico-City, significant differences were only found in three antigens of the HLA-B locus. On the other hand, comparison of either series from Mexico-city with the Los Angeles or the San Antonio studies yielded discrepancies in several specificities of both HLA-A and B loci, most notably the consistent absence of A25 in Mexican Mestizos living in Mexico-City. The presence of this specificity in the Mexican Mestizo Population living in these two American cities could have resulted from input of Caucasian and Black genes over several generations. Differences in haplotype frequency were observed comparing the two series from Mexico-City and the series from San Antonio. Comparison of haplotype frequency with the Los Angeles series was not possible.

Ethnicity↗

Bactericidal capacity of newborn phagocytes against group B beta-hemolytic streptococci.

The bactericidal capacity of mononuclear and polymorphonuclear phagocytes obtained from normal newborn infants and from healthy adults was evaluated in vitro, using two group B beta-hemolytic streptococci (GBBHS) serotypes (GBBHS-Ia-SS-615/28 and GBBHS-III-SS-620/50) and uniform opsonic conditions. No intertype differences in bacteriolysis of these two serotypes were observed among leukocytes from newborns or adults. As group, only polymorphonuclear phagocytes from newborns disclosed a significantly lower mean bactericidal capacity than their adult cellular counterpart, and only with respect to GBBHS-III-SS-620/50. On the other hand, 4 or 16 polymorphonuclear samples from newborns tested revealed significantly low bactericidal capacities against both GBBHS serotypes, and an additional sample revealed a bactericidal capacity against GBBHS-III-SS-620/50 alone. Interstrain variations in the intrinsic bactericidal capacity of polymorphonuclear phagocytes from newborns against GBBHS-III may exist, as suggested by a single observation made by using four clinical isolates of GBBHS-III. Such deviant phagocytic capacities of polymorphonuclear phagocytes from newborns may constitute an additional selective risk factor in the genesis of GBBHS sepsis of the newborn.

Adult↗

Effect of Fusarium toxins, T2-toxin and diacetoxyscirpenol on murine T-independent immune responses.

Trichothecenes mycotoxins, T2-toxin and diacetoxyscirpenol were investigated for their effect upon T-independent murine immune responses. Both anti-polyvinylpyrrolidone and anti-dinitrophenylficoll responses were enhanced by chronic administration of these toxins. Spleen cells from T2-toxin-treated animals revealed significantly less Thy 1.2+ cells than controls. Spleen cells from Fusarium crude extract-treated animals had a depressed response to phytohaemagglutinin (PHA) as compared with controls. Normal recipients given spleen cells from T2-toxin-treated mice were shown to generate approximately 50% less plaque-forming cells against sheep red blood cells than controls. It is suggested that these effects occur as a result of altered T suppressor-cell function.

Animals↗