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Biomedical subjects

R Berger

Publications and source records attributed to R Berger.

At least 739 records · Page 41Linked to original sources

A topological and functional model of epitopes on the structural glycoprotein of tick-borne encephalitis virus defined by monoclonal antibodies.

A topological and functional model of eight distinct epitopes on the structural glycoprotein of tick-borne encephalitis (TBE) virus was established by the use of monoclonal antibodies. The unique specificities and spatial relationships of these antibodies were determined by variant analysis, haemagglutination inhibition (HI), neutralization, passive mouse protection, and antibody blocking assays. Seven out of the eight distinct epitopes were shown to be partially linked and to cluster in two antigenically reactive domains (A, B). Each of these domains is inhomogeneous and contains constituents with different serological specificities and functions. Domain A is defined by three HA-inhibiting antibodies, two of which are flavivirus group-reactive, whereas the third is TBE virus subtype specific. Within this domain only the subtype-specific antibody is involved in virus neutralization, thus explaining the observation that neutralization tests with flaviviruses show higher serological specificities than HI tests and that HI tests can be made type and subtype specific by antibody absorption. Domain B is composed of three TBE-complex reactive epitopes, and the corresponding antibodies inhibit HA and neutralize the virus. A fourth epitope linked to this domain is neither involved in HA nor in neutralization and the same holds true for a subtype-specific epitope which is topologically independent of domains A and B. Each of two different nonneutralizing antibodies was capable of blocking the binding of distinct neutralizing antibodies. All eight epitopes are indistinguishably present on strains of the western subtype of TBE virus isolated all over Europe in different years from different hosts, thus again confirming the great stability of this virus.

Animals↗

Interferon-gamma production by Listeria monocytogenes-specific T cells active in cellular antibacterial immunity.

Cultures of peritoneal exudate T lymphocyte-enriched cells (PETLEC) from Listeria monocytogenes-immune mice, antigen-presenting cells (APC) and heat-killed L. monocytogenes produced high amounts of interferon-gamma (IFN-gamma). High IFN titers were also observed after stimulation of L. monocytogenes-immune cell cultures with the T cell mitogens concanavalin A and phytohemagglutinin. L. monocytogenes-immune PETLEC produced several fold higher IFN titers than normal cell cultures in response to mitogen and antigen. Under both circumstances, APC were required for optimum responses. L. monocytogenes-immune PETLEC participating in IFN production were Lyt 1+23-. IFN-gamma was also produced in cultures of cloned L. monocytogenes-specific T cells. Since the same T cell clone showed antigen-specific proliferative responses and interleukin production in vitro, and could adoptively mediate delayed-type hypersensitivity and anti-listerial protection in vivo, it is suggested that IFN production is a function of specific T cells active in cellular antibacterial immunity.

Animals↗

Absence of hepatic molybdenum cofactor: an inborn error of metabolism leading to a combined deficiency of sulphite oxidase and xanthine dehydrogenase.

Five patients with a combined deficiency of xanthine dehydrogenase, sulphite oxidase and, possibly, also of aldehyde oxidase are described. This remarkable coincidence of three inborn errors of metabolism in a single individual was demonstrated to result from a deficiency of the 'molybdenum cofactor', an essential constituent of all three enzymes. The main biochemical findings in these patients included: hypouricaemia, xanthinuria, an increased excretion of sulphite, thiosulphate and S-SUL-sulphocysteine and a decreased excretion of inorganic sulphate. Plasma molybdenum was normal. The ultimate diagnosis was made by the measurement of 'molybdenum cofactor' in a liver biopsy specimen in three out of five patients. The clinical hallmarks in these patients were: feeding difficulties, mental retardation, neurological symptoms, lens dislocation, an abnormal muscle tone, myoclonia and an abnormal physiognomy. The majority of these were already present in the neonatal period. So far, attempts at treatment have been unsuccessful.

Child, Preschool↗

Cytological types of mitoses and chromosome abnormalities in acute leukemia.

In order to determine the nature of the cells in mitosis in acute leukemia, a parallel study was conducted by cytological and cytogenetic methods on the same marrow and blood samples. On direct marrow examination, erythrocyte precursors in mitosis are usually observed but ordinarily disappear following in vitro culture. In APL (M3) characterized by t(15;17) translocation, the comparison between the proportions of the different categories of cells in mitosis and of karyotypically normal and abnormal cells suggests that erythroblasts do not belong to the leukemic clone. An analogous situation is observed in AML (M2) with t(8;21) and in monocytic leukemia (M5) with chromosome abnormalities. Erythroleukemia could be divided into two categories, one with chromosome abnormalities and persistence of erythroblast mitoses after culture, and another with no detectable chromosome abnormality and with disappearance of erythroblast mitoses following culture. Other examples of blood malignancies demonstrate the importance of the method used in determining which cell categories belong to the leukemic clone. An interpretation of the results in terms of commitment 'level' of the involved stem cells and a distinction between 'primary' and 'secondary' chromosome abnormalities is proposed.

Acute Disease↗

C-band pattern in lymphocytes of patients with soft tissue sarcomas.

The pattern of heteromorphisms in the C-band-positive constitutive heterochromatin of human chromosomes No. 1, 9, and 16 was studied in peripheral lymphocytes of 45 patients with soft tissue sarcomas and 78 control individuals. The parameters of the heterochromatic regions analyzed were relative size, symmetry-asymmetry within homologous pairs, and incidence of inversions. No consistent differences were found in these parameters between controls and sarcoma patients.

Chromosome Banding↗

t(15;17) in a promyelocytic form of chronic myeloid leukemia blastic crisis.

Two simultaneous translocations, t(15;17) and t(9;22), have been observed in a chronic myelogenous leukemia patient with acute promyelocytic blastic crisis. After remission obtention only karyotypes with t(9;22) were present. The occurrence of the two translocations in the same cell argues in favor of the specificity of t(15;17) versus acute promyelocytic differentiation.

Adult↗

Malignant and reactive erythroblasts in erythroleukemia (M6).

A cytogenetic and cytological study of 16 cases of erythroleukemia (M6) is reported. No chromosomal abnormalities were observed in 10 cases. Abnormalities were present in the other 6 cases, of which 4 were complex abnormalities. It was not possible to establish any correlation between the occurrence of morphologic abnormalities of the erythroid and megakaryocyte-platelet series and the presence of cytogenetic defects. Studies of mitoses by cytologic and cytogenetic methods concurrently performed in some cases suggest that two types of erythroleukemia can be distinguished: (1) cases with chromosomal abnormalities and a persistence of erythroblast mitoses in vitro (which suggests that the erythroblasts belong to the leukemic clone) and (2) cases with no chromosome abnormality and a disappearance of erythroblast mitoses after culture, suggesting that the erythroblasts are not members of the leukemic clone.

Adult↗

Cytogenetic studies on Burkitt's lymphoma cell lines.

Cytogenetic findings on 15 new cell lines established from endemic and nonendemic Burkitt's lymphoma are reported. Specific translocations t(8;14) and t(8;22) were found, respectively, in 13 and in 2 of the cell lines. Particular attention has been paid to the additional chromosome abnormalities found in 10 of the 15 cell lines. These anomalies involve the long arm chromosome No. 1 with a relatively high frequency. These additional chromosome anomalies argue in favor of the concept of the existence of primary and secondary chromosome abnormalities in malignancies.

Adolescent↗

A reliable screening test for childhood celiac disease: fluorescent immunosorbent test for gliadin antibodies. A prospective multicenter study.

The diagnostic value of gliadin antibody determination using the fluorescent immunosorbent test was examined in a prospective multicenter study comprising 251 children with malabsorptive disorders. Antibodies to gliadin were found in all 72 patients (100%) with active celiac disease (29 children with celiac disease proved by challenge, 43 with probable celiac disease). All children up to the age of 7 years had antibodies in high titers. By contrast, 96 (84%) of 114 children with other malabsorptive disorders and a normal mucosa or with partial villous atrophy had no gliadin antibodies, 14 (12%) had a low titer, and only four (3.5%) showed moderate to high titers. Four children with gastrointestinal tract symptoms of cow milk intolerance and a flat mucosa also showed no antibodies. In 24 of 29 children (83%) with cystic fibrosis and six of seven children with Crohn disease (biopsies not performed in either group), no antibodies could be detected. The others had low or elevated titers. In 25 children with acute gastroenteritis (not biopsied) antibodies were not found at hospital admission nor six weeks later after reintroduction of gluten. The determination of antibodies to gliadin with the fluorescent immunosorbent test is a reliable screening test for childhood celiac disease. In our series there were no false negative results in children with untreated celiac disease. A positive gliadin antibody titer is not proof of celiac disease. In each child the diagnosis must be confirmed by small intestinal biopsy even if the gliadin antibody titer is high. The detection of high titers of cow milk antibodies in 27% of patients with celiac disease is of no value.

Adolescent↗

Production of interferon-gamma in the syngeneic mixed lymphocyte reaction.

Cocultures of nylon wool-separated, non-adherent (T enriched) mouse spleen cells with mitomycin C-treated adherent cells resulted in the production of antiviral activity in the culture supernatants. This antiviral activity was defined as interferon gamma (IFN-gamma) because of its lability at pH 2 and the susceptibility to inactivation by anti mouse IFN-gamma antibodies. Treatment of non-adherent cells with anti-Thy 1.2 or anti-Lyt 1.2 antibody plus complement abolished IFN production. In contrast, anti-Lyt 2.2 plus complement treatment had no effect on IFN production. Abrogation of IFN production was also seen when anti-Ia antibodies were added. IFN could be observed in the SMLR, regardless of the H-2 haplotype of the mouse strains with the exception of NZB mice. Addition of hydrophilic polymers such as polyethyleneglycol or DEAE-dextran enhanced IFN production.

Animals↗

Direct hybridization of sorted human chromosomes: localization of the Y chromosome on the flow karyotype.

A method is described for directly hybridizing a small number of sorted chromosomes with specific DNA probes. The chromosomes are analyzed by flow cytometry and sorted by deflecting the droplets containing the desired chromosomes onto a nitrocellulose filter. By using probes specific for the human Y chromosome, it has been possible to unambiguously identify the peak corresponding to the Y chromosome in the flow karyotypes of a variety of male cell lines. The position of this peak was found to vary significantly from individual to individual, correlating with the heterochromatin chromosomal polymorphism of the human Y chromosome. The sensitivity of the hybridization was such that, with a probe for a male-specific repetitive sequence, only 2,500 sorted chromosomes were enough to obtain a clear, positive signal; 10,000 were needed with a probe specific for a weakly repeated (maximum, 3-fold) sequence of Y chromosome. With this new method, chromosome sorting may be a rapid and efficient way to assign DNA sequences to chromosomes.

Burkitt Lymphoma↗

In vitro effects of cyclosporin A on human B-cell responses.

The in vitro effects of cyclosporin A (CsA) on T-cell-dependent and T-cell-independent mitogen responses of human B cells were studied. T-cell-dependent, pokeweed mitogen (PWM)-induced B-cell proliferation and B-cell differentiation to Ig-secreting cells were significantly inhibited by CsA, when purified B cells were cultured with T-cell helper factor containing supernatants instead of T cells. This indicates that the inhibitory effect of CsA on T-cell-dependent, PWM-induced B-cell proliferation and differentiation is not exclusively due to direct effects on helper T cells. B-cell proliferations induced by anti-IgM antibodies and by Staphylococcus aureus bacteria were also found to be sensitive to CsA. Since both types of reactions are T-cell-independent, the concept that responses of human B cells can also be affected by CsA in ways that seem to be independent of the well-documented direct effects of CsA on T cells is further supported. This seems not to be a general phenomenon, however. Epstein-Barr-virus-induced activation of human B cells, as reported previously and also observed by us, is completely insensitive to CsA. It seems, therefore, that certain B-cell activation mechanisms are sensitive to CsA while others remain unaltered. The difference between these two reaction patterns cannot be exclusively explained by a T-cell dependence or T-cell independence of these responses. CsA effects on certain functional B-cell subsets or interference with accessory cell mechanisms might be responsible.

Antibody-Producing Cells↗

Use of survival analysis to determine the clinical significance of new Q waves after coronary bypass surgery.

There are few data on the long-term effects of new Q waves on survival and morbidity after coronary bypass graft surgery (CABG). We followed 1340 patients who underwent CABG in 1978 at 10 hospitals participating in the Coronary Artery Surgery Study (CASS). The incidence of perioperative Q-wave infarction was 4.76% (range 0.0-10.3% by hospital). The rate of infarction was higher in patients who had an increased left ventricular end-diastolic pressure or cardiomegaly on the preoperative chest radiograph. Patients who received more grafts or who had longer cardiopulmonary bypass time were also at higher risk of infarction. In a stepwise discriminant analysis of 44 clinical, angiographic and surgical variables, cardiopulmonary bypass time, topical cardiac hypothermia and cardiomegaly entered the stepwise selection of variables. Long-term survival was adversely affected by the appearance of new postoperative Q waves. The hospital mortality was 9.7% in the 62 patients who had new postoperative Q waves and 1.0% in the 1278 patients who did not (p less than 0.001); the 3-year cumulative survival rates were 85% and 95%, respectively (p less than 0.001). In patients who survived to hospital discharge, the presence of new postoperative Q waves did not adversely affect 3-year survival (94% and 96%, respectively). The survival rates were worse in patients who had a history of infarction or who had impaired left ventricular function preoperatively. The number of readmissions to hospital after CABG among the patients who had a transmural perioperative infarction was similar to to that among patients who did not. We conclude that the appearance of new Q waves after CABG adversely affects survival. The major impact on mortality occurs before hospital discharge. Patients who are destined to have a perioperative infarct cannot be predicted from commonly measured preoperative and angiographic variables.

Adult↗

Effect of feeding human milk on nosocomial rotavirus infections in an infants ward.

Children aged 1-15 months hospitalized for different respiratory diseases (including otitis media) at an infants ward frequently developed diarrhoea during their stay in the clinic. Bacteriological examinations of stool samples were usually negative but rotavirus excretion was frequent according to ELISA tests. Children fed with human milk are assumed to be less susceptible to rotavirus infections due to the protection by maternal antibody. In view of preventive measures for avoiding rotavirus nosocomial infections a study was carried out. All children entering the infants ward and showing no sign of gastrointestinal disorders were distributed at random into two groups. The first group received a normal diet according to age, the second group received in addition 200 ml of fresh human milk per day. Serial stool samples were taken at the first day and thereafter every 3-4 days. Routine bacteriological examination and tests for rotavirus excretion were carried out. Children already excreting rotavirus at the first day were excluded from the study. Analysis of the gene segments of excreted rotavirus revealed the presence of two subspecies of rotavirus type 2 appearing at different periods during the study indicating nosocomial infections. Such infections were surprisingly frequent: 16 of 28 children started to excrete rotavirus during their stay in the ward and 8 of these 16 got diarrhoea. A statistically significant difference in the infection rate between the two groups was not observed although clinical symptoms seemed to be less severe in children fed with human milk.

Cross Infection↗