Search PubMed⌕ Search

Biomedical subjects

A Jauch

Publications and source records attributed to A Jauch.

At least 37 records · Page 2Linked to original sources
PubMed2000

Allelic changes at multiple regions of chromosome 5 are associated with progression of urinary bladder cancer.

This study has analysed 65 urothelial carcinomas for allelic imbalance at 22 loci of chromosome 5 and has determined three regions of interest. A commonly duplicated region was mapped to chromosome 5p between loci D5S1473 and D5S819, one region of deletion to chromosome 5q22-23 between loci D5S2055 and D5S659, and another to chromosome 5q33-34 between loci D5S1456 and D5S1465. An allelic imbalance was detected in 54% of the cases. Only 10% of grade 1 tumours showed allelic changes at chromosome 5, whereas 60% and 63% of grade 2 and grade 3 cancers, respectively, had alterations of chromosome 5. The frequency of chromosome 5 changes increased from 24% in pTa tumours up to 72% in pT3-4 tumours. Of particular interest, ten out of 12 urothelial carcinomas showing metastatic growth in regional lymph nodes at the time of cystectomy had alterations at chromosome 5. No specific region, but genetic changes in general were associated with the grading and staging of bladder cancers.

Alleles↗
PubMed2000

Becker muscular dystrophy combined with X-linked Charcot-Marie-Tooth neuropathy.

A man was identified with two X-chromosomal neuromuscular disorders, X-linked Charcot-Marie-Tooth disease (CMTX) and Becker muscular dystrophy (BMD). The neuropathy could be tracked in the family and was found to be caused by a mutation in the connexin32 gene on Xq13. 1. The muscular dystrophy was sporadic owing to a de novo deletion in the dystrophin gene located in band Xp21.2. Although these genetic alterations of the same X-chromosome are considered as physically independent, their combination resulted in a unique phenotype with severe wasting of proximal as well as distal muscles and rapid progression of both conditions.

Adult↗
PubMed2000

Multiplex FISH telomere integrity assay identifies an unbalanced cryptic translocation der(5)t(3;5)(q27;p15.3) in a family with three mentally retarded individuals.

Cryptic rearrangements involving the terminal regions of chromosomes are suspected to be the cause of idiopathic mental retardation in a significant number of cases. This finding highlights the necessity of a primary screening test for such chromosome aberrations. Here we present a multiplex fluorescence in situ hybridization telomere integrity assay which allows the detection of submicroscopic aberrations in the telomeric regions of all chromosomes. This novel approach identified an unbalanced cryptic translocation der(5)t(3;5)(q27;p15.3) in a family with three cases of unexplained mental retardation and dysmorphic features. The symptoms of the patients represent neither the classical dup(3q)- nor cri du chat syndrome, although all affected individuals demonstrate several features of both syndromes. The identification of two balanced translocation carriers emphasizes the significance of the telomere integrity assay for genetic counseling and prenatal diagnosis.

Adult↗
PubMed2000

Diclofenac drops to treat inflammation after cataract surgery.

PURPOSE: To compare the anti-inflammatory effect of topical diclofenac sodium 0.1% in a fixed combination with gentamicin 0.3% to the anti-inflammatory effect of dexamethasone phosphate 0.1% in a prospective randomized double-masked double-dummy study in patients undergoing cataract surgery. SETTING: Trial performed from June 1991 to April 1992 at the Hôpital Jules Gonin, Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland. METHODS: Inclusion of patients scheduled for extracapsular cataract extraction (ECCE) with implantation of an all PMMA intraocular lens (IOL). Double-masked comparison of post-operative inflammation in two randomized treatment groups: (1) fixed diclofenac sodium 0.1%/gentamicin 0.3% and vehicle drops 4X/day until day 12-14 and diclofenac sodium 0.1% 3X/day until day 28. (2) dexamethasone phosphate 0.1% drops 4X/day until postoperative day 12-14 and 3X/day until day 28 and gentamicin 0.3% drops 4X/day until day 12-14. Anterior chamber flare and cells, measured by laser flare-cell photometry, were analyzed as the primary outcomes. RESULTS: Eighty-seven patients were recruited, 45 being assigned to the diclofenac group and 42 to the dexamethasone control group. Diclofenac was significantly better than dexamethasone at controlling flare at day 3 (p< or =0.01) and day 12-14 (p< or =0.002). Mean anterior chamber cells were also significantly lower at day 12-14 (p< or =0.021) and day 28 (p< or =0.012). The commonest adverse event was transient punctate keratitis, which occurred in 15 diclofenac and 3 dexamethasone patients. CONCLUSIONS: While both treatments were effective at controlling post-operative inflammation, the diclofenac-gentamicin combination followed by diclofenac alone was significantly better at suppressing flare and cells but showed a slightly higher incidence of punctate keratitis and eye discomfort.

Aged↗
PubMed2000

Identification of a subtle t(16;19)(p13.3;p13.3) in an infant with multiple congenital abnormalities using a 12-colour multiplex FISH telomere assay, M-TEL.

There is increasing evidence that cytogenetically invisible chromosome rearrangements are an important cause of genetic disease. Clues to the chromosomal location of these rearrangements may be provided by a specific clinical diagnosis, which can then be investigated by targeted FISH or molecular studies. However, the phenotypic features of some microdeletion syndromes are difficult to recognise, particularly in infants. In addition, the presence of other chromosome aneuploidy may mask the typical clinical features. In the present study, the presence of tubers on cranial magnetic resonance imaging (MRI) of a 5-week-old infant prompted an investigation, by FISH, with probes from the tuberous sclerosis gene, TSC2. This and further FISH deletion mapping studies revealed a submicroscopic deletion encompassing the entire TSC2 gene and the adjacent PKD1 gene on one chromosome 16, confirming a del(16)(p13.3). Because of the large number of abnormal phenotypic features in this infant, we performed a 12-colour FISH assay (M-TEL) to screen for subtelomeric rearrangements involving the del(16p). The M-TEL assay revealed a cryptic der(16)t(16;19)(p13.3;p13.3). Further FISH with 19p and 19q subtelomeric probes demonstrated that this was derived from a balanced maternal t(16;19)(p13.3;p13.3). Importantly, 24-colour painting by multiplex FISH (M-FISH) failed to detect the translocation in either the infant or his mother. Based on our FISH mapping studies, we estimate the size of the trisomic region from 19p13.3 to be approximately 2 Mb, and the region of monosomy for 16p13.3 as 2.25 Mb. This case adds to the growing literature which indicates that many apparent chromosomal deletions are unbalanced translocations. The M-TEL assay provides a sensitive alternative to M-FISH for the detection of these subtle telomeric rearrangements.

Abnormalities, Multiple↗
PubMed2000

Genetic characterization of a human skin carcinoma progression model: from primary tumor to metastasis.

The type and number of genetic aberrations required for a fully malignant tumor are still unclear. This study describes the genetic analysis of a series of skin squamous cell carcinomas, representing the primary tumor, two recurrences, and a metastatic lesion from a single patient and cell lines established therefrom (MET-1 to MET-4). Comparative genomic hybridization demonstrated that: (i) most of the gains and losses were common for tumors and cell lines and affected chromosomes 3 (3p loss, 3q gain), 5 (5p gain, 5q loss), 7 (7p gain), 8 (8p loss, 8q gain), 11 (11q gain), and 17 (17p loss), and (ii) only one aberration was present in a tumor but not in the cell line (10 loss in tumor 4); and only few aberrations were cell line specific. From these, 10p loss and 17q gain were shared by all lines and tumor 4, suggesting that they were already present in all tumors, although in only a subpopulation of cells, whereas 20q gain (shared by all lines), 4q loss (MET-2), and 18p gain/18q loss (MET-3) seem to be culture derived. In agreement, multiplex fluorescence in situ hybridization demonstrated a set of common translocations for all lines thereby further confirming their common origin. In addition, each cell line, exhibited one or more individual translocation chromosomes, which suggested that MET-1 was a precursor of MET-4, whereas MET-2 and MET-3 developed in parallel. Whereas MET-1 to MET-3 were hypodiploid or hyperdiploid, MET-4 was characterized by polyploidization, a set of specific aberrations (t(3;7), t(X;2), i(10q)), and increased heterogeneity (varying translocations in individual metaphases). Using sequencing and expression studies, cells from all lines were wild type for p53, did not exhibit mutations in any of the ras genes (Harvey, Kirsten, or N-ras), and expressed wild-type fragile histidine triad gene (FHIT; mapped to 3p14.2, a locus underrepresented in all cells) transcripts. Thus, with the MET cell lines we present an in vivo skin carcinoma progression model that was genetically well defined, and which, despite originating from a sun-exposed site, is wild type for p53.

Carcinoma, Squamous Cell↗
PubMed1999

Syndromal obesity due to paternal duplication 6(q24.3-q27).

The likelihood of a paternally expressing imprinted gene in chromosome region 6(q23-24) has been highlighted by cases of transient neonatal diabetes mellitus (TNDM) in which paternal uniparental disomy (UPD) for chromosome 6 or paternal duplication 6(q23-qter) was detected. We present the case of a 38-year-old man with moderate to severe intellectual delay, short stature, small hands and feet, eye abnormality, small mouth, and obesity (without hyperphagia) beginning in mid-childhood. The perinatal and neonatal histories were normal. The patient had a duplication within 6q. Fluorescence in situ hybrisation studies were performed with single and dual hybridisations using a chromosome 6 library probe, short and long arm subregional probes, 6q23-24, 6q25.3-6qter locus-specific probes, and a 6q telomere probe. The hybridisation results defined an inverted duplication of 6q24.3 to 6q27. DNA studies with microsatellite markers from 6p and 6q showed regular biparental inheritance of chromosome 6 and confirmed that the duplication was paternal in origin. Our patient appears to be the first one known to have paternal duplication of chromosome area 6(q24-q27) who did not have TNDM as an infant. He has remained nondiabetic, although obesity, without hyperphagia, has been a constant problem since its onset in mid-childhood.

Adult↗
PubMed1999

Duplication within chromosome 5q characterized by fluorescence in situ hybridization.

We present a 16-month-old boy with developmental delay, minor anomalies, small penis, and lymphedema of the upper limbs. Routine cytogenetic analysis suspected a duplication of 5q. Fluorescent in situ hybridization (FISH) with a cosmid probe (MCC at the 5q22 APC region) showed tandemly duplicated fluorescent signals on one of chromosomes 5, whereas FISH with three YAC probes (TYAC12 at 5q35, HTY3182 at 5q34, and TYAC139 at 5q31) did not give duplicated signals. These findings indicate a duplication of 5q22 band in one chromosome 5. The boy we describe here is the first case of a pure partial duplication of 5q to be proven by FISH techniques. A review of previously reported cases of putative partial 5q duplication showed no consistent phenotype.

Abnormalities, Multiple↗
PubMed1999

Léri-Weill syndrome as part of a contiguous gene syndrome at Xp22.3.

We report on a mother and her 5-year old son, both with a terminal deletion of the short arm of the X chromosome. By molecular genetic analysis the breakpoint was located distal to steroid sulfatase gene. The boy manifested, due to nullisomy of this region, short stature (SHOX), chondrodysplasia punctata (ARSE), and mental retardation (putative mental retardation gene MRX 49). Short stature is present in mother and son, but both also had bilateral Madelung deformity, a key finding in the Léri-Weill syndrome. We discuss the phenotype in relationship to hitherto published cases with chromosomal aberrations and contiguous gene syndromes of Xp22.3.

Abnormalities, Multiple↗
PubMed1999

Chromosomal abnormalities in renal cell neoplasms associated with acquired renal cystic disease. A series studied by comparative genomic hybridization and fluorescence in situ hybridization.

Sporadic renal cell carcinomas (RCCs) display different chromosomal abnormalities according to their morphology; gains of chromosomes 7 and 17 and loss of Y are commonly observed in papillary lesions, whereas loss of 3p sequences and multiple losses of specific chromosomes are found in non-papillary and chromophobe cell carcinomas, respectively. Acquired renal cystic disease (ARCD) is associated with an increased incidence of renal cell tumours, especially papillary lesions. The aim of this study was to examine a series of ARCD-related tumours for chromosomal abnormalities and to compare the findings with those abnormalities commonly observed in sporadic RCCs. Nine tumours from four patients with ARCD were examined using comparative genomic hybridization (CGH) and interphase cytogenetics. Gain of chromosomes 7 and 17 was observed in all four papillary lesions and loss of Y in three. In addition, gain of chromosome 16 was observed in three papillary tumours. Three chromophobe RCCs originating from the same kidney showed different genomic profiles; two had no abnormalities, whereas one showed loss of chromosome 17p. Two non-papillary RCCs failed to show chromosome 3p alterations. In conclusion, renal cell tumours developing in ARCD may show chromosomal abnormalities both similar to and different from those seen in sporadic tumours.

Adult↗
PubMed1999

Meta-analysis of six clinical phase III studies comparing lomefloxacin 0.3% eye drops twice daily to five standard antibiotics in patients with acute bacterial conjunctivitis.

BACKGROUND: Lomefloxacin 0.3% ophthalmic solution twice daily has been compared in patients with bacterial conjunctivitis in six randomized double-blind or investigator-masked phase III studies with either chloramphenicol 0.5% 5x/day, gentamicin 0.3% 4x/day, fusidic acid 1% 2x/day, tobramycin 0.3% 4x/day or norfloxacin 0.3% 4x/day. METHODS: A meta-analysis of all individual data of these six studies was performed. A total of 582 patients with clinically diagnosed bacterial conjunctivitis were evaluated by slit-lamp examination with grading of eight key signs and symptoms and by conjunctival swab cultures at baseline, on day 3-5 and on day 7-9. Success of therapy, local tolerance and safety were evaluated at termination. In vitro sensitivity of the ocular isolates to 6-10 antibiotics was evaluated by disk diffusion tests. RESULTS: Two hundred and ninety patients treated with lomefloxacin 0.3% (LF) and 292 patients treated by one of the control antibiotics (combined control group, CCG) were enrolled in the studies. Two hundred and seventy-eight LF and 283 CCG patients were evaluable for the intent-to-treat (ITT) analysis, while 85 LF and 95 CCG patients had bacteria above the pathological threshold and formed the core subpopulation. The mean cumulative sum score in the LF group was 9. 47 on day 1, and decreased by 5.70 on day 3-5 and by 8.10 on day 7-9. In the CCG it decreased significantly less: it was 9.19 at baseline, decreased by 5.15 on day 3-5 and by 7.33 on day 7-9. Swab counts decreased in the LF and CCG group similarly, with the major decrease observed between day 1 and day 3-5. Most of the organisms considered resistant in vitro were still eradicated with the regimen used. Of the few surviving organisms also isolated on the next follow-up visit, one isolate in the LF group and seven in the CCG showed decreased in vitro sensitivity towards the treatment antibiotic used. Local tolerance was good or excellent, without any significant differences except for burning sensation, which lasted significantly longer in the CCG group than in the LF group. Adverse events were observed in 18 LF and 23 CCG patients; four LF and three CCG patients had to be withdrawn. All adverse events were non-serious. CONCLUSION: Lomefloxacin eye drops used with a loading dosage followed by a twice daily regimen proved as effective, safe and well tolerated as five established standard treatments used at a 2, 4 or 5 times daily regimen, caused less discomfort upon instillation, and showed a lower risk to generate or select new resistant strains.

Acute Disease↗
PubMed1999

Topical lomefloxacin 0.3% twice daily versus tobramycin 0.3% in acute bacterial conjunctivitis: A multicenter double-blind phase III study.

AIMS/BACKGROUND: To evaluate in a double-masked comparative, prospective, randomized multicenter trial the efficacy of lomefloxacin 0.3% eye drops twice daily and of tobramycin eye drops 4 times daily in patients with acute bacterial conjunctivitis. METHODS: Ninety-nine subjects were enrolled: 50 were treated with lomefloxacin 0.3% eye drops twice daily and 49 with tobramycin 0.3% eye drops 4 times daily. In all patients, conjunctival swabbing and assessment of objective signs and of subjective symptoms were performed. RESULTS: There was no statistical difference for any individual sign or symptom or for the sum score of either key or other signs and symptoms at any of the examination days. The sum score of both key and other signs and symptoms decreased in both groups at day 3-4 as compared to baseline values (p < 0.0001). The decrease in both these scores continued significantly from day 3-4 to day 7-8 (p < 0.05) and was similar in the two treatment groups (p > 0.4). The lowest resistance rate was seen in lomefloxacin (3.5%) and in neomycin (7.0%), while tobramycin showed resistance in 10 out of 88 resistance strains (11.4%). CONCLUSION: Both lomefloxacin 0.3% twice daily and tobramycin 0.3% administered 4 times daily were well tolerated and showed a high degree of clinical and microbiological efficacy in the treatment of acute bacterial conjunctivitis. Lomefloxacin caused less resistance than other antibiotics evaluated.

Acute Disease↗
PubMed1999

Mapping the gene causing hereditary primary hyperparathyroidism in a Portuguese kindred to chromosome 1q22-q31.

A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism (HPT) that was associated with parathyroid adenomas and carcinomas was investigated with the aim of determining the chromosomal location of this gene, designated HPTPort. Leukocyte DNA from 9 affected and 16 unaffected members and 7 parathyroid tumors from 4 patients was used in comparative genomic hybridization (CGH), tumor loss of heterozygosity (LOH), and family linkage studies. The CGH studies revealed abnormalities of chromosomes 1 and 13, and the results of LOH studies were consistent with the involvements of tumor suppressor genes from these regions. Family segregation studies mapped HPTPort to chromosome 1q22-q31 by establishing linkage with eight loci (D1S254, D1S222, D1S202, D1S238, D1S428, D1S2877, D1S422, and D1S412) (peak two-point LOD scores = 3. 46-5.14 at 0% recombination), and defined the location of HPT Port to a 21 cM region flanked centromerically by D1S215 and telomerically by D1S306. Thus, HPTPort has been mapped to chromosome 1q22-q31, and a characterization of this gene will help to elucidate further the mechanisms that are involved in the development of parathyroid tumors.

Adenoma↗
PubMed1998

Spatial distributions of early and late replicating chromatin in interphase chromosome territories.

The surface area of chromosome territories has been suggested as a preferred site for genes, specific RNAs, and accumulations of splicing factors. Here, we investigated the localization of sites of replication within individual chromosome territories. In vivo replication labeling with thymidine analogues IdUrd and CldUrd was combined with chromosome painting by fluorescent in situ hybridization on three-dimensionally preserved human fibroblast nuclei. Spatial distributions of replication labels over the chromosome territory, as well as the territory volume and shape, were determined by 3D image analysis. During late S-phase a previously observed shape difference between the active and inactive X-chromosome in female cells was maintained, while the volumes of the two territories did not differ significantly. Domains containing early or mid to late replicating chromatin were distributed throughout territories of chromome 8 and the active X. In the inactive X-chromosome early replicating chromatin was observed preferentially near the territory surface. Most important, we established that the process of replication takes place in foci throughout the entire chromosome territory volume, in early as well as in late S-phase. This demonstrates that activity of macromolecular enzyme complexes takes place throughout chromosome territories and is not confined to the territory surface as suggested previously.

Cells, Cultured↗
PubMed1998

Evidence against a looped structure of the inactive human X-chromosome territory.

Multicolor fluorescence in situ hybridization with a whole chromosome composite probe for the X-chromosome and microdissection probes for the Xp and Xq arms, as well as for the Xp terminal, Xq terminal, and X centromer specific subregional probes, was applied to three-dimensional (3D) preserved human female amniotic fluid cell nuclei. Confocal laser scanning microscopy and three-dimensional image analysis demonstrated distinctly separated Xp arm and Xq arm domains. 3D distance measurements revealed a high variability of intrachromosomal distances between Xpter, Xcen, and Xqter specific probes within both X territories. A 3D distance measurement error of +/- 70 nm was found in control experiments using quartz glass microspheres labeled with different fluorochromes. Our data argue against the hypothesis of Walker et al. (1991, Proc. Natl. Acad. Sci. USA 88, 6191-6195) that a looped structure of the inactive X territory is formed by tight telomere-telomere associations.

Female↗
PubMed1998

An evolutionarily conserved gene on human chromosome 5q33-q34, UBH1, encodes a novel deubiquitinating enzyme.

While cloning breakpoint sequences of a leukemia patient exhibiting a t(5; 14) translocation, we identified a pseudogenic variant of a novel multigene family in proximity to the breakpoint. Chromosomal in situ hybridization suggested that the gene family is clustered on human chromosome 5q33-q34. The gene family is evolutionarily conserved. Northern blot analysis of mouse tissues revealed low-level expression of a functional member of this gene family in almost all samples. Marked levels of transcripts were detected by in situ hybridization in the retina, the olfactory epithelium, the peripheral neuronal ganglia, and distinct areas of the gut. The predicted protein displays striking similarity to a hypothetical protein of Caenorhabditis elegans (R10E11.3.) and to two yeast deubiquitinating enzymes, Ubp9 and Ubp13, albeit to a lesser extent. We expressed the putative coding region of the human gene in Escherichia coli and demonstrated that it indeed bears deubiquitinating activity based on its ability to cleave ubiquitin from a ubiquitin-beta-galactosidase fusion protein. This new deubiquitinating enzyme has been named UBH1, for ubiquitin hydrolyzing enzyme 1.

Amino Acid Sequence↗
PubMed1998

Noonan-like phenotype in monozygotic twins with a duplication-deficiency of the long arm of chromosome 18 resulting from a maternal paracentric inversion.

We report on newborn monozygotic twins with a Noonan-like phenotype, and multiple congenital anomalies due to a monocentric recombinant chromosome 18. The mother carried a paracentric inversion of the long arm of chromosome 18, inv(18)(q21.1q22.3). Cytogenetic, fluorescent in situ hybridization, comparative genomic hybridization and DNA marker analyses allowed the delineation of the deleted (18q22.3-qter) and duplicated (18q12.1-q21.1) chromosomal regions in the recombinant chromosome 18, and suggest that this duplication-deletion chromosome 18 resulted from breakage of a dicentric recombinant chromosome 18 with subsequent reconstitution of telomeric sequences on the long arm. Marked variability is observed in the phenotypic expression of the same chromosomal anomaly in these monozygotic twins. The clinical findings of these patients are compared with those reported in proximal 18q-duplication and distal 18q-deletion patients. The clinical features of both infants are compatible with Noonan syndrome, suggesting that a locus for this syndrome may be located on the long arm of chromosome 18.

Chromosome Deletion↗