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M Gessler

Publications and source records attributed to M Gessler.

At least 37 records · Page 2Linked to original sources
PubMed1992

[Parasitological and immunological progress control during and after chemotherapy of canine leishmaniasis].

Promastigote Leishmania-organisms were diagnostically cultivated in vitro from popliteal lymph node aspirates obtained from 32 of in total 36 dogs returning from endemic areas. Isoenzyme analysis (glucosephosphate-isomerase (GPI), phosphoglucomutase (PGM) and glutamate-oxaloacetate-transaminase (GOT) resulted in the identification of Leishmania infantum (syn. Leishmania (L.) infantum) for all 18 isolates investigated. Parasites were still able to be cultivated in vitro in 79% of 28 biopsies (from 15 dogs) even following chemotherapy by Glucantime, independent of the time of sampling and the course of disease after treatment. Dogs with a progressive form of disease (despite chemotherapy) showed only a minor or no reduction (between 0 and 4.8%) of the relative antibody concentration (determined by ELISA), whereas regressive forms of disease (without recurrences observed in the period of 10 to 37 months after therapy) demonstrated a marked reduction of the relative antibody concentration (between 6.7 and 16.2%) within the first 5 to 8 months; thereafter the decrease diminished and changed to a persistent low relative antibody concentration.

Animals↗
PubMed1991

GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families.

The Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder affecting limb and craniofacial development in humans. GCPS-affected individuals are characterized by postaxial polysyndactyly of hands, preaxial polysyndactyly of feet, macroephaly, a broad base of the nose with mild hypertelorism and a prominent forehead. The genetic locus has been pinpointed to chromosome 7p13 by three balanced translocations associated with GCPS in different families. This assignment is corroborated by the detection of two sporadic GCPS cases carrying overlapping deletions in 7p13 (ref. 7), as well as by tight linkage of GCPS to the epidermal growth factor receptor gene in 7p12-13 (ref. 8). Of the genes that map to this region, those encoding T cell receptor-gamma, interferon-beta 2, epidermal growth factor receptor, and Hox1.4, a potential candidate gene for GCPS, have been excluded from the region in which the deletions overlap. Here we show that two of the three translocations interup the GLI3 gene, a zinc-finger gene of the GLI-Krüppel family already localized to 7p13 (refs 5, 6). The breakpoints are within the first third of the coding sequence. In the third translocation, chromosome 7 is broken at about 10 kilobases downstream of the 3' end of GLI3. Our results indicate that mutations disturbing normal GLI3 expression may have a causative role in GCPS.

Chromosome Deletion↗
PubMed1991

A new photometric assay for testing trypanocidal activity in vitro.

A new in vitro test was developed to assess the trypanocidal activity of compounds against axenically grown Trypanosoma brucei bloodstream forms. Trypanosomes from continuous culture were exposed to series of drug dilutions in a microtiter plate. After an incubation time of 72 h at 37 degrees C, the pH indicator of the medium had changed its colour in non-inhibited cultures due to the production of pyruvate. Inhibited cultures showed less, if any, colour changes. Plates could be read by eye or using an enzyme-linked immunosorbent assay (ELISA) reader. Within the pH range of 7.0-7.5, the extinction values of phenol red at 560 nm showed a linear correlation with both the pH of the medium and the pyruvate concentration in the medium. By comparison of the decreases in extinction in test cultures with those in control cultures, IC50 values (drug concentrations causing 50% inhibition) could be determined. Minimal inhibitory concentrations (MICs) could be read by eye. The photometric test evaluation was compared with evaluation according to growth inhibition or to incorporation of radiolabelled hypoxanthine. The three methods of evaluation gave similar results.

Animals↗
PubMed1991

A somatic cell hybrid panel and DNA probes for physical mapping of human chromosome 7p.

To identify by reverse genetics genes on the short arm of human chromosome 7 expected to be involved in the regulation of human craniofacial and limb development, we have set up a human mouse somatic cell hybrid panel that divides 7p into 9 fragments. The breakpoints are defined by deletions or translocations involving one chromosome 7 in the cells of the human cell fusion partners. Particularly densely covered with these cytogenetic anchor points is the proximal area of 7p within and around 7p13. The number of cytogenetic mapping points within proximal 7p could be increased by four, using two diploid human cell lines with small interstitial deletions in this region for dosage studies. We used Southern blots of this panel to assign to 7q or subregions of 7p more than 300 arbitrary DNA probes or genes that provide reference points for physical mapping of 7p. Three reciprocal translocations with one of the breakpoints in 7p13 mark the location of a gene involved in Greig cephalopolysyndactyly syndrome. To define an area in which we could identify candidates for this developmental gene, we established a macrorestriction map using probes flanking the putative gene region. The Greig translocations were found to be located within a 630-kb NotI restriction fragment.

Animals↗
PubMed1990

Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping.

Cytogenetic analysis has identified chromosome 11p13 as the smallest overlap region for deletions found in individuals with WAGR syndrome, which includes Wilms tumour (a recessive childhood nephroblastoma), aniridia, genito-urinary abnormalities and mental retardation. The underlying loci have since been resolved into an aniridia (AN2) locus at a telomeric position, and a locus of closely spaced genes or a single pleiotropic gene involved in genito-urinary tract abnormalities and Wilms tumour at a more centromeric position. Pulsed-field gel analysis of the 11p13 region has revealed the presence of several putative CpG islands, structures which are frequently associated with the 5' ends of expressed sequences, mainly housekeeping genes and some tissue-specific genes. Starting from a CpG island, we have now isolated four neighbouring CpG islands, all within 650 kilobases (kb), by means of two consecutive bidirectional jumps in rare-cutting restriction-enzyme jumping libraries. In two instances, flanking sequences were conserved in other species and RNA transcripts were identified. A complementary DNA clone isolated for one of them derives from an RNA highly expressed in fetal kidney, and is predicted to encode a Krüppel-like zinc-finger protein that is probably a transcription factor. The entire cDNA region is included in two partially overlapping homozygous deletions found in Wilms tumour DNA samples. Cloning of the breakpoints in one tumour revealed a deletion size of 170 kb, one-third of which is covered by the cDNA. The expression pattern and sequence of this cDNA could point to an important role for its corresponding gene in the normal development of the renal system as well as in Wilms tumour.

Amino Acid Sequence↗
PubMed1990

The human MyoD1 (MYF3) gene maps on the short arm of chromosome 11 but is not associated with the WAGR locus or the region for the Beckwith-Wiedemann syndrome.

The human gene encoding the myogenic determination factor myf3 (mouse MyoD1) has been mapped to the short arm of chromosome 11. Analysis of several somatic cell hybrids containing various derivatives with deletions or translocations revealed that the human MyoD (MYF3) gene is not associated with the WAGR locus at chromosomal band 11p13 nor with the loss of the heterozygosity region at 11p15.5 related to the Beckwith-Wiedemann syndrome. Subregional mapping by in situ hybridization with an myf3 specific probe shows that the gene resides at the chromosomal band 11p14, possibly at 11p14.3.

Animals↗
PubMed1990

Role for the Wilms tumor gene in genital development?

Detailed molecular definition of the WAGR region at chromosome 11p13 has been achieved by chromosome breakpoint analysis and long-range restriction mapping. Here we describe the molecular detection of a cytogenetically invisible 1-megabase deletion in an individual with aniridia, cryptorchidism, and hypospadias but no Wilms tumor (WT). The region of overlap between this deletion and one associated with WT and similar genital anomalies but no aniridia covers a region of 350-400 kilobases, which is coincident with the extent of homozygous deletion detected in tumor tissue from a sporadic WT. A candidate WT gene located within this region has recently been isolated, suggesting nonpenetrance for tumor expression in the first individual. The inclusion within the overlap region of a gene for WT predisposition and a gene for the best-documented WT-associated genitourinary malformations leads us to suggest that both of these anomalies result from a loss-of-function mutation at the same locus. This in turn implies that the WT gene exerts pleiotropic effect on both kidney and genitourinary development, a possibility supported by the observed expression pattern of the WT candidate gene in developing kidney and gonads.

Aniridia↗
PubMed1989

Cloning of breakpoints of a chromosome translocation identifies the AN2 locus.

Chromosome translocations involving 11p13 have been associated with familial aniridia in two kindreds highlighting the chromosomal localization of the AN2 locus. This locus is also part of the WAGR complex (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation). In one kindred, the translocation is associated with a deletion, and probes for this region were used to identify and clone the breakpoints of the translocation in the second kindred. Comparison of phage restriction maps exclude the presence of any sizable deletion in this case. Sequences at the chromosome 11 breakpoint are conserved in multiple species, suggesting that the translocation falls within the AN2 gene.

Chromosome Deletion↗
PubMed1989

A physical map around the WAGR complex on the short arm of chromosome 11.

A long-range restriction map of part of the short arm of chromosome 11 including the WAGR region has been constructed using pulsed-field gel electrophoresis and a number of infrequently cutting restriction enzymes. A total of 15.4 Mbp has been mapped in detail, extending from proximal 11p14 to the distal part of 11p12. The map localizes 35 different DNA probes and reveals at least nine areas with features characteristic of HTF islands, some of which may be candidates for the different loci underlying the phenotype of the WAGR syndrome. This map will furthermore allow screening of DNA from individuals with WAGR-related phenotypes and from Wilms tumors for associated chromosomal rearrangements.

Animals↗
PubMed1989

A deletion map of the WAGR region on chromosome 11.

The WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) region has been assigned to chromosome 11p13 on the basis of overlapping constitutional deletions found in affected individuals. We have utilized 31 DNA probes which map to the WAGR deletion region, together with six reference loci and 13 WAGR-related deletions, to subdivide this area into 16 intervals. Specific intervals have been correlated with phenotypic features, leading to the identification of individual subregions for the aniridia and Wilms tumor loci. Delineation, by specific probes, of multiple intervals above and below the critical region and of five intervals within the overlap area provides a framework map for molecular characterization of WAGR gene loci and of deletion boundary regions.

Abnormalities, Multiple↗
PubMed1988

Molecular mapping and cloning of the breakpoints of a chromosome 11p14.1-p13 deletion associated with the AGR syndrome.

Chromosome 11p13 is frequently rearranged in individuals with the WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) or parts of this syndrome. To map the cytogenetic aberrations molecularly, we screened DNA from cell lines with known WAGR-related chromosome abnormalities for rearrangements with pulsed field gel (PFG) analysis using probes deleted from one chromosome 11 homolog of a WAGR patient. The first alteration was detected in a cell line from an individual with aniridia, genitourinary anomalies, mental retardation, and a deletion described as 11p14.1-p13. We have located one breakpoint close to probe HU11-164B and we have cloned both breakpoint sites as well as the junctional fragment. The breakpoints subdivide current intervals on the genetic map, and the probes for both sides will serve as important additional markers for a long-range restriction map of this region. Further characterization and sequencing of the breakpoints may yield insight into the mechanisms by which these deletions occur.

Cell Line↗
PubMed1987

Follow-up studies of three subtypes of acute postinfectious glomerulonephritis ascertained by renal biopsy.

Quantitative correlative investigations by means of light, immunofluorescence and electron microscopy carried out in the early phase of the disease on 58 patients (children and adults) with acute postinfectious glomerulonephritis (APGN) formed the basis of subtyping APGN into a starry sky type, a mesangial type and a garland type [Sorger et al. 1982 and 1983]. The subtypes also showed differences in the clinical picture. The garland type was of special interest since most patients had severe proteinuria. This caused us to follow-up the patients with these three subtypes (up to 10 years and 7 months). Proteinuria proved to be the most reliable follow-up parameter. A comparison of the three groups showed that proteinuria rapidly declined as a rule in the patients with the starry sky and the mesangial patterns. In the garland pattern there were also cases with a complete disappearance of proteinuria, especially in younger patients, but other patients still had a distinct proteinuria after months to years indicating a protracted or chronic course. The morphological findings of the rebiopsies correlated with the clinical courses, especially with the course of proteinuria. The three morphological subtypes are thus significant for estimating the prognosis of APGN, which is favorable as a rule in patients with the starry sky and mesangial types, but much more unfavorable in patients with the garland type. Even if fewer cases with demonstrated streptococcal etiology were found in the garland pattern group, i.e., among patients with the most uncertain prognosis, than in the remaining groups, these differences were not statistically significant. Therefore, our investigations do not provide any indications that different etiological factors are responsible for the three subtypes. The individual immune response of the host body is likely to be very much more decisive.

Acute Disease↗
PubMed1986

Activation of the pp60c-src kinase during differentiation of monomyelocytic cells in vitro.

The proto-oncogene c-src, the cellular homolog of the Rous sarcoma virus (RSV) transforming gene v-src, is expressed in a tissue-specific and age-dependent manner. Its physiological function, although still unknown, appears to be more closely related to differentiation processes than to proliferation processes. To obtain more information about the physiological role of the c-src gene in cells, we have studied differentiation-dependent alterations using the human HL-60 leukaemia cell line as a model system. Induction of monocytic and granulocytic differentiation of HL-60 cells by 12-O-tetradecanoylphorbol-13-acetate (TPA) and dimethylsulfoxide (DMSO) is associated with an activation of the pp60c-src tyrosine kinase, but not with increased c-src gene expression. Control experiments exclude an interaction of TPA and DMSO themselves with the pp60c-src kinase.

Avian Sarcoma Viruses↗
PubMed1984

Differential expression of the cellular oncogenes c-src and c-yes in embryonal and adult chicken tissues.

The cellular onc-genes c-src and c-yes are expressed very differently during chicken embryonic development. The c-src mRNA and its translational product are detectable at high levels in brain extracts of chicken embryos and adult chickens, whereas muscle extracts show an age-dependent decrease in the amounts of c-src-specific mRNA and pp60c-src kinase activity. In contrast, the levels of c-yes mRNA in brain, heart, and muscle are relatively low in early embryonic stages and increase later on to values comparable to those found for liver, while in adult animals the pattern of c-yes expression is similar to that of the c-src gene. From the close correlation between the levels of pp60c-src, its enzymatic activity, and its corresponding mRNA at a given stage of development and in given tissues, it appears that the expression of pp60c-src is primarily controlled at the level of transcription. It is suggested that because of the different patterns of expression, the two cellular oncogenes, c-src and c-yes, play different roles in cell proliferation during early embryonic stages as well as in ensuing differentiation processes.

Aging↗
PubMed1982

[Relations between fox populations and halting the rabies in North Rhine-Westphalia].

Since Sylvatic rabies started in North Rhine-Westphalia in 1953 many epidemics have occurred, only in mid-mountain areas. As a characteristic, epidemics halted, in each case at the limit between big game (in south-east) and small game (in the north-west) hunting areas. The fact that rabies died out when reaching these limits is surprising for, according to the number of foxes killed in small game hunting areas, there was a fox density which usually does not allow the epidemic to stop. Explanation of this phenomenon could be the different hunting methods. Indeed in small game hunting areas 80% of killed foxes are cubs or sub-adults. Which means that most of the growing population is destroyed early enough, in contrast with big game hunting areas where less than half of the killed foxes are cubs or sub-adults. This is why in big game hunting areas, better conditions are found for rabies appearance than in the other type of hunting area. Studying the number of foxes killed, these relations are described for three regions of North Rhine-Westphalia. It is obviously very important in rabies control that, besides other measures, growing foxes are killed in priority.

Animals↗