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Biomedical subjects

R Scherrer

Publications and source records attributed to R Scherrer.

17 recordsLinked to original sources
PubMed1992

Type beta transforming growth factors promote interleukin-3 (IL-3)-dependent differentiation of human basophils but inhibit IL-3-dependent differentiation of human eosinophils.

Basophils and eosinophils share a common differentiation pathway. Factors regulating terminal commitment toward one cell type, however, have so far not been defined. Interleukin-3 (IL-3) is a potent differentiation factor for both human eosinophils and basophils. In the present study, the effects of various recombinant human (rh) growth regulators on IL-3-dependent growth of eosinophils and basophils were studied in a bone marrow (BM) suspension culture system (normal donors, n = 13). We found that type beta transforming growth factors (TGFs) lead to a significant increase in the absolute numbers of basophils in BM cultures grown in the presence of IL-3 (day 14 of culture; IL-3: 133 +/- 20 v IL-3 + TGF-beta 1: 231 +/- 28 x 10(3)/mL [P less than .01]) and to an increase in the total histamine values (IL-3: 72.6 +/- 22.2 v IL-3 + TGF-beta 1: 142.9 +/- 37.3 ng/mL [P less than .015]) compared with rhIL-3 alone. In contrast, type beta TGFs were found to inhibit the IL-3-dependent growth of eosinophils (IL-3: 170.4 +/- 37.2 v IL-3 + TGF-beta 1: 16.7 +/- 5.2 x 10(3)/mL [P less than .01]) and formation of eosinophil cationic protein in the same culture system. The effect of TGF-beta 1 (and TGF-beta 2) on IL-3-dependent differentiation of basophils and eosinophils was dose- and time-dependent (maximum effects observed with 1 to 10 ng/mL of rhTGF-beta 1 or TGF-beta 2) and could be neutralized by an antibody specific for TGF-beta 1. In contrast to the TGFs, interferon-alpha (IFN-alpha) and IFN-gamma were found to downregulate IL-3-dependent formation of both basophils (IL-3: 167 +/- 33 v IL-3 + IFN-alpha: 67 +/- 25 v IL-3 + IFN-gamma: 65 +/- 33 x 10(3)/mL [P less than .01]) and eosinophils (IL-3: 239 +/- 5 v IL-3 + IFN-alpha: 81 +/- 4 v IL-3 + IFN-gamma: 67 +/- 17 x 10(3)/mL [P less than .05]) in our culture system. Type beta TGFs as well as the IFNs failed to directly induce differentiation of human basophils or eosinophils in the absence of other growth factors. Together, these results show that type beta TGFs and IFNs are potent regulators of cytokine-dependent growth and differentiation of human allergic effector cells.

Antibodies, Monoclonal↗
PubMed1992

Detection of circulating endogenous interleukin-3 in extensive chronic graft-versus-host disease.

Recent data suggest that activated immune cells and their products are involved in the initiation and progression of graft-versus-host disease (GVHD). To test whether the production of endogenous interleukin-3 (IL-3), a product of activated immune cells, might be an indicator of disease activity in GVHD, we analysed sera of 61 bone marrow transplant (BMT) recipients for IL-3 levels by using an enzyme linked immunosorbent assay. Measurable levels (greater than 25 pg/ml) of endogenous IL-3 were detected in a significant subgroup (5/16 patients, 31.25%) of allograft recipients suffering from extensive chronic GVHD, but not in patients with limited chronic GVHD (n = 6) or in those without signs of chronic GVHD (n = 17). In IL-3 positive patients, IL-3 levels were not associated with pathologic conditions (such as infectious disease) other than GVHD. IL-3 levels were undetectable in disease-free phases preceding severe chronic GVHD. Lower levels of IL-3 were measured in chronic GVHD patients during extensive disease while on high dose steroid medication compared with before and/or after (p less than 0.02). IL-3 was also detected in a small group (2/17) of patients suffering from acute GVHD. IL-3 could neither be detected in syngeneic (n = 3) nor autologous (n = 7) BMT recipients nor in the vast majority (99/100) of healthy controls. Together, measurable amounts of IL-3 are produced in a significant subgroup of patients suffering from extensive chronic GVHD.

Adolescent↗
PubMed1991

MDR1 gene expression and treatment outcome in acute myeloid leukemia.

To prospectively assess the role of MDR1 gene expression in patients with de novo acute myeloid leukemia (AML), levels of MDR1 RNA in blast cells were determined at diagnosis and correlated with treatment outcome in 63 patients. MDR1 RNA levels were negative in 29% and positive in 71% of the patients. The complete remission rate in response to induction chemotherapy was 89% for MDR1 RNA-negative patients and 53% for MDR1 RNA-positive patients (P = .008). Expression of the MDR1 gene was observed in most patients who died early or had resistant disease. Kaplan-Meier curves revealed a decrease in both disease-free survival and overall survival of patients with detectable MDR1 gene expression compared with the disease-free survival and overall survival of MDR1 RNA-negative patients (P = .029 and P = .009, respectively). These data indicate that MDR1 gene expression is an unfavorable prognostic factor and suggest that multidrug resistance is important in AML.

Adolescent↗
PubMed1991

Hepatic and splenic abscesses--a common complication of intensive chemotherapy of acute myeloid leukemia (AML). A prospective study.

In order to determine the frequency of hepatosplenic abscesses in AML patients during chemotherapy and to evaluate the clinical and laboratory characteristics of this complication we performed a prospective study over a 28-month period. Fifty-five consecutive patients with de novo AML or relapse who received intensive chemotherapy underwent regular ultrasound examinations. In 16 patients (29.1%) hepatic and/or splenic abscesses were detected sonographically. Histopathological evidence for abscess formation was obtained in five of these 16 patients. In three patients granulation tissue and in one patient necrotizing granulomas were found. Causative micro-organisms were proven in only three patients: Candida hyphae were demonstrated in one patient, gram-positive cocci in another. Bacteria and fungi were seen in the tissue specimen of the third patient. Patients with hepatosplenic abscesses had significantly prolonged fever after neutrophil recovery but did not differ from patients without abscesses in any other laboratory or clinical features. Due to the absence of specific alerting clinical and laboratory signs and symptoms of hepatosplenic abscesses, routine ultrasound examination is required for detection of this complication. The presence of hepatic and/or splenic abscesses does not necessarily worsen the prognosis, but it may influence the decision on further chemotherapy and antimicrobial treatment.

Abscess↗
PubMed1979

[Hyperventilation and airway resistance. Bronchial spasms after hyperventilation].

Airway resistance, FEV1.0 and lung volume were measured by body plethysmography before and after voluntary hyperventilation. In normal subjects, resistance increased to 130--140% of the initial value measured before hyperventilation. The same increase was observed in silicosis patients without chronic obstructive bronchitis. Asthmatic patients in an asymptomatic phase showed a rise in airway resistance to an average of 255% of the nearly normal initial values, and also a reduction in FEV1.0. In normal subjects and asthmatic patients, the administration of bronchodilators inhibits the rise in airway resistance induced by hyperventilation. The hyperventilation test can be used to identify increased susceptibility to bronchoconstriction.

Asthma↗
PubMed1979

Activation of rotavirus RNA polymerase by calcium chelation.

Two types of particles were isolated during purification of rotavirus. Dense (D) particles have a density of 1.38 in CsCl and exhibit spontaneously a fully active endogenous transcriptase. Light (L) particles (density of 1.36 in CsCl) need to be treated with chelating agents to show a polymerase activity. The activation process of L particles was studied under strictly controlled monovalent, divalent, and hydrogen ion concentrations. These experiments demonstrate that i) activation is not affected by the ionic strength ii) activation occurs only at a pH higher than 7.1 iii) a low concentration of chelating agent (40 muM EDTA) is sufficient to activate the enzyme. Treatment of particles with EGTA, which chelates selectively Ca2+, leads to unmasking even in the presence of magnesium, indicating that the concentration of free calcium ions plays a major role in the activation process. Various glycosidases, detergents, and chelating agents were tested in respect to unmasking properties. Of these compound only chelating agents turned out to be efficient. Following activation, two glycopeptides were solubilized. These glycopeptides have an apparent molecular weight of 34,000 and 31,000 daltons and react with concanavalin A. The role of Ca2+ upon the stability of virus particles, and the activation of the endogenous transcriptase in vitro and in the infected cells is discussed.

Animals↗
PubMed1979

Infantile gastroenteritis caused by rotavirus: comparison of enzyme-linked immunosorbent assay and electron microscopy for rapid diagnosis.

ELISA and negative contrast EM have used for the detection of rotavirus in one hundred stools from children, less than two years old, hospitalized for acute gastro-enteritis during the winter 1977-78. Samples obtained from the same children some months after hospitalization were also tested. A good correlation was found between the results given by EM and ELISA, but the later technique turned out to be more sensitive (12% more positive using ELISA). A rotavirus infection could be demonstrated in 73% of the patients. In the stools of 3 children we found a second virus in association with the rotavirus, and in two cases a pathogenic bacterium. When a second serum specimen was available from children previously infected by rotavirus it was always possible to detect a significant increase in CF antibodies. Several months after hospitalization a 2nd survey indicated that the rotavirus was no longer present but calicivirus, echovirus, coxsackievirus and adenovirus could be detected in those asymptomatic children.

Antibodies, Viral↗
PubMed1978

The experimental production of diarrhoea in colostrum deprived axenic and gnotoxenic calves with enteropathogenic Escherichia coli, rotavirus, coronavirus and in a combined infection of rotavirus and E. coli.

We attempted to produce diarrhoea experimentally in the newborn calf by orally injecting 17 colostrum-deprived calves with two serotypes of Escherichia coli Ent+ K99+, a rotavirus and a coronavirus. With E. coli alone, a dose of 2 x 10(8) bacteria administered 24 hours after birth causes a mild attack of diarrhoea, whereas 1 x 10(10) bacteria leads to dehydration and death. An inoculation of rotavirus is followed by diarrhoea which always contains large quantities of rotavirus. These animals were anorectic for a time, but none was dehydrated or died. With coronavirus, there were large quantities of watery diarrhoea, which led to dehydration and death. The inoculation of rotavirus, not lethal in itself, followed by a similarly non lethal inoculation of E. coli in doses of 3 x 10(8) to 2 x 10(9) led to dehydration and death. The authors conclude that dehydration and death of the animal can caused by large doses of E. coli or coronavirus or by two non-lethal doses of rotavirus and E. coli administered one after the other.

Animals↗
PubMed1977

Density, porosity, and structure of dried cell walls isolated from Bacillus megaterium and Saccharomyces cerevisiae.

Helium displacement and nitrogen adsorption techniques were used to determine the density and porosity, respectively, of freeze-dried cell walls isolated from Bacillus megaterium KM and Saccharomyces cerevisiae. The densities were 1.302 and 1.180 g/cm3, respectively, suggesting noncrystalline solids. The porosities were extremely small, indicating that the cell walls had collapsed and become essentially impervious upon lyophilization.

Bacillus megaterium↗
PubMed1976

Fine structure of the Baccilus thuringiensis spore.

The thin-sectioned spore of Bacillus thuringiensis resembles that of Bacillus cereus in fine structure. Planar inclusions occur between the exosporium and spore coat and are structured differently from the parasporal crystal outside the exosporium.

Bacillus cereus↗
PubMed1976

[In vitro culture of a rotavirus associated with neonatal calf diarrhea].

About fifty diarrheic fecal samples in which the calf rotavirus was present in variable quantities were passed in tissue cultures and the ability of the virus to replicate was analysed under different experimental conditions by means of an indirect immunoflourescent test. Several cell species were shown to be susceptible to the virus but the best results were obtained in primary or secondary cultures of embryonic calf kidney cells in presence of maintainance medium containing 2 to 4 p. 100 foetal calf serum or chick serum. The specific infectivity of this type of virus is low in tissue culture. Under the best experimental conditions about 70 p. 100 of the samples that were positive for the virus by electron microscopy, induced the appearance of specifically fluorescent cells. Cytopathic effects due to infection are extremely discreet and most often there is no evidence of transfer of infection from cell to cell. Different attempts to adapt the infective agent to grow in tissue culture finally succeeded in the selection of a virus that was able to induce fluorescnet plaques at the fifth pass.

Animals↗
PubMed1976

Reovirus-like agent (rotavirus) associated with neonatal calf gastroenteritis in France.

A reo-like virus (calf rotavirus) was shown to be associated with cases of neonatal calf diarrhea in France. The virus could be detected in more than 50 p. 100 of diarrheic fecal samples, while it was practically absent in control samples originating from healthy calves that had never had diarrhea. The results obtained by electron microscopy and immunofluorescent studies indicate that the virus is closely related or identical to the agent isolated originally in the United States.

Animals↗
PubMed1975

Studies on infectious pancreatic necrosis virus interactions with RTG-2 and FHM cells: selection of a variant virus-type in FHM cells.

Evidence is presented that adaptation of IPN virus (strain VR 299) to FHM cells entails the selection of a variant virus type that differs significantly from the parental, and most representative, RTG-2 virus type in being able to adsorb efficiently to, and form plaques in, FHM cells. The plaque titre of FHM-non-adapted virus stocks (RTG-2 viruses) was reduced by at least 99-99% in FHM cells, while FHM-adapted virus stocks (FHM viruses) produced plaques at equally high titres in both RTG-2 and FHM cells. FHM viruses and RTG-2 viruses differed also in their behavior in RTG-2 cells in respect to plaque size distribution and growth characteristics, but both virus-types were shown to be morphologically identical, and no significant difference in reactivity against specific antiserum could be detected. Analysis of virus in individual RTG-2 plaque isolates or plaque progeny shows that a mutation of relatively high frequency (10(-4) to 10(-5))robably causes the ability to infect the FHM cells efficiently. Only these mutant virus-types were found in FHM plaque isolates.

Animals↗