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Biomedical subjects

S Gerber

Publications and source records attributed to S Gerber.

At least 73 records · Page 4Linked to original sources
PubMed1997

MRI of pituitary adenomas in acromegaly.

Adenomas causing acromegaly represent at least a quarter of pituitary adenomas. We studied 12 patients presenting with active acromegaly due to a pituitary adenoma with a 1.5 T superconductive MRI unit. All had T1-weighted sagittal and coronal sections before and after Gd-DTPA; six had coronal T2-weighted images. Surgical correlation was obtained in seven patients. Histologically, there were eight growth hormone (GH)-secreting and three mixed [GH and prolactin (PRL) secreting] adenomas, and one secreting GH, PRL and follicle-stimulating hormone. Macroadenomas (10) were more frequent than microadenomas (2). No correlation was found between serum GH and tumour size. There were nine adenomas in the lateral part of the pituitary gland; seven showed lateral or infrasellar invasion. Homogeneous, isointense signal on T1- and T2-weighted images was observed in six cases. Heterogeneous adenomas had cystic or necrotic components.

Acromegaly↗
PubMed1997

Oligonucleotide-directed mutagenesis and subsequent expression of the corresponding recombinant proteins without changing the bacterial vector system.

A new bacterial vector was constructed that combines the attractive features of gene fusion vectors and phagemids. A gene of interest cloned into this new vector can either be expressed as fusion protein or be prepared as single-stranded template DNA within the same system. Thus, time consuming subcloning procedures changing the bacterial vector according to the required method are avoided. As an example sequencing, expression and subsequent purification of site-directed mutants of herpes simplex virus type 1 thymidine kinase are discussed.

Cloning, Molecular↗
PubMed1997

Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB.

Usher syndrome is recognized as the most frequent cause of hereditary deaf-blindness. Usher syndrome type I (USH1), the most severe form of the disease, is characterized by profound congenital sensorineural deafness, constant vestibular dysfunction, and retinitis pigmentosa of prepubertal onset. This form is genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar. However, only the gene responsible for USH1 B (which accounts for approximately 75% of USH1 cases) has been characterized. It encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence. Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequence were designed, allowing direct sequence analysis of each of the 48 coding exons and flanking splice sites in seven patients affected by USH1. Four novel mutations were thereby identified. The possibility should now be considered of a sequence-based prenatal diagnosis in some of the families affected by this very severe form of Usher syndrome.

Base Sequence↗
PubMed1997

A newly identified locus for Usher syndrome type I, USH1E, maps to chromosome 21q21.

Usher syndrome (USH) is a clinically and genetically heterogeneous disorder characterized by congenital hearing loss combined with retinitis pigmentosa. This dual sensorineural deficiency is transmitted in an autosomal recessive mode. Usher syndrome type I (USH1) is the most severe form. Four loci responsible for USH1 (USH1A, 1B, 1C and 1D) have previously been mapped, among which only the USH1B gene has been cloned. Using homozygosity mapping in a consanguineous family from Morocco, we identified a novel locus for USH1, USH1E, mapping to chromosome band 21q21. The delimited 15 cM interval is flanked by the loci D21S1905 and D21S1913. Subsequent segregation analysis of two families affected by USH1, in which the A, B, C and D loci had been excluded, also excluded the involvement of the USH1E locus, therefore indicating the existence of at least one more locus for USH1.

Child↗
PubMed1997

Severe manifestations in carrier females in X linked retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of progressive hereditary disorders of the retina in which various modes of inheritance have been described. Here, we report on X linked RP in nine families with constant and severe expression in carrier females. In our series, however, the phenotype was milder and delayed in carrier females compared to hemizygous males. This form of X linked RP could be regarded therefore as partially dominant. The disease gene maps to chromosome Xp2.1 in the genetic interval encompassing the RP3 locus (Zmax=13.71 at the DXS1100 locus). Single strand conformation polymorphism and direct sequence analysis of the retinitis pigmentosa GTPase regulator (RPGR) gene, which accounts for RP3, failed to detect any mutation in our families. Future advances in the identification of X linked RP genes will hopefully help to elucidate the molecular basis of this X linked dominant RP.

Adolescent↗
PubMed1996

A new method for quantitative determination of tritium-labeled nucleoside kinase products adsorbed on DEAE-cellulose.

The counts of tritiated compounds--adsorbed to paper disks, paper chromatograms, electrophoretograms or TLC plates--can be strongly affected by extended self-absorption of tritium beta-particles on the matrix, due to their low energy. Therefore fully quantitative results can be obtained only by elution of the substances or decomposition of the matrix and subsequent counting in homogeneous solution. In this study we describe a new method for fast and proper decomposition of cellulose matrices by cellulase digestion prior to scintillation counting. This new approach yields up to 98% recovery. For method validation recombinant herpes simplex type 1 thymidine kinase was characterised kinetically. The Km of 0.2 microM remained the same as expected but Vmax was considerably higher yielding 1050 pmol/microgram/min.

Adsorption↗
PubMed1996

Asbestos exposure and ovarian fiber burden.

Epidemiologic studies suggest increased risk of epithelial ovarian cancer in female asbestos workers and increased risk of malignancy in general in household contacts of asbestos workers. Ovaries were studied from 13 women with household contact with men with documented asbestos exposure and from 17 women undergoing incidental oophorectomy. Ovarian tissue was examined by analytic electron microscopy. Significant asbestos fiber burdens were detected in 9 out of 13 women with household asbestos exposure (69.2%), and in 6 out of 17 women who gave no exposure history (35%). Three exposed women had asbestos counts over 1 million fibers per gram wet weight (23%), but only 1/17 women without an exposure history had a count that high (6%). Although asbestos has been documented as a contaminant of some older cosmetic talc preparations, the chrysotile and crocidolite types of asbestos we detected are more indicative of background and/or occupational exposure. This study demonstrates that asbestos can reach the ovary. Although the number of subjects is small, asbestos appears to be present in ovarian tissue more frequently and in higher amounts in women with a documentable exposure history.

Asbestos↗
PubMed1996

Evidence of genetic heterogeneity of Leber's congenital amaurosis (LCA) and mapping of LCA1 to chromosome 17p13.

Leber's congenital amaurosis (LCA) is an autosomal recessive disease responsible for congenital blindness. It is the earliest and most severe inherited retinal dystrophy in human and its genetic heterogeneity has long been recognised. We have recently reported on the first localisation of a disease gene (LCA1) to the short arm of chromosome 17 by homozygosity mapping in five families of North African origin. Here, we refine the genetic mapping of LCA1 to chromosome 17p13 between loci D17S938 and D17S1353 and provide strong support for the genetic heterogeneity of this condition (maximum likelihood for heterogeneity, 17.20 in InL; heterogeneity versus homogeneity, P = 0.0002, heterogeneity versus no linkage, P < 0.0001)

Blindness↗
PubMed1996

Long-term MR follow-up of cerebral lesions in neuro-Behçet's disease.

To study the long-term evolution of cerebral lesions in neuro-Behçet's disease, MRI was carried out on 12 patients, with follow-up from 1.5 to 6 years (mean 3.5 years). On the first MRI, 66 lesions in all were found; each patient had 1-10 lesions (mean 5.5). There were 30 (46%) lesions in the brain stem, 18 (27%) in the basal ganglia region and 18 (27%) in the periventricular white matter. Of these 22 (33%) were small, 31 (47%) medium-size and 13 (20%) large lesions. On the last MRI, 60 lesions were found: each patient had 1-10 lesions (mean 5). At this time 31 lesions (52%) were in the brain stem, 13 (22%) in the basal ganglia region and 16 (26%) in the periventricular white matter. There were 41 (68%) small, 13 (22%) medium-size and 6 (10%) large lesions. About 40% of the lesions disappeared, 35% reduced in size and 25% remained unchanged. No lesion had enlarged. Of the 60 final lesions 20 (34%) were not observed on the first study. Small new lesions were found in 5 of 12 patients (42%), and were asymptomatic. Medium-size or large new lesions were found in 2 patients (17%) who had stopped steroid treatment and had a neurological relapse. Enlargement of the ventricular system or worsening of initial cerebral atrophy was observed in 9 of 12 patients. Appearance of small lesions and worsening of cerebral atrophy on long-term follow-up suggest the possibility of subclinical progression of cerebral vasculitis and should be considered in the prognosis of neuro-Behçet's disease.

Adolescent↗
PubMed1996

Retinitis punctata albescens associated with the Arg135Trp mutation in the rhodopsin gene.

PURPOSE: To screen for mutations in the rhodopsin, peripherin/RDS, and ROM1 genes in a family affected with retinitis punctata albescens. Because clinical heterogeneity was observed in this family, with some members affected with retinitis punctata albescens and one member affected with features typical of retinitis pigmentosa, we analyzed the apolipoprotein E gene to elucidate this unusual intrafamilial heterogeneity. METHODS: The coding sequences of these genes were analyzed with a combination of single-strand conformation polymorphism and direct sequence analysis. Haplotypes of the apolipoprotein E gene were analyzed by polymerase chain reaction and enzymatic digestion. RESULTS: The Arg135Trp mutation in the rhodopsin gene was observed in all affected members of this family, but no mutation was detected in the peripherin/RDS or ROM1 genes. The e4 allele of the apolipoprotein E gene apparently cosegregated with the albescens phenotype in this family. CONCLUSIONS: The albescent phenotype in retinal dystrophy appears to not be caused exclusively by a peripherin/RDS gene mutation, and we suggest that the apolipoprotein E gene may play a role in the albescent phenotype.

Adolescent↗
PubMed1996

Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis.

Leber's congenital amaurosis (LCA, MIM 204,000), the earliest and most severe form of inherited retinopathy, accounts for at least 5% of all inherited retinal dystrophies. This autosomal recessive condition is usually recognized at birth or during the first months of life in an infant with total blindness or greatly impaired vision, normal fundus and extinguished electroretinogram (ERG). Nystagmus (pendular type) and characteristic eye poking are frequently observed in the first months of life (digito-ocular sign of Franceschetti). Hypermetropia and keratoconus frequently develop in the course of the disease. The observation by Waardenburg of normal children born to affected parents supports the genetic heterogeneity of LCA. Until now, however, little was known about the pathophysiology of the disease, but LCA is usually regarded as the consequence of either impaired development of photoreceptors or extremely early degeneration of cells that have developed normally. We have recently mapped a gene for LCA to chromosome 17p13.1 (LCA1) by homozygosity mapping in consanguineous families of North African origin and provided evidence of genetic heterogeneity in our sample, as LCA1 accounted for 8/15 LCA families in our series. Here, we report two missense mutations (F589S) and two frameshift mutations (nt 460 del C, nt 693 del C) of the retinal guanylate cyclase (RETGC, GDB symbol GUC2D) gene in four unrelated LCA1 probands of North African ancestry and ascribe LCA1 to an impaired production of cGMP in the retina, with permanent closure of cGMP-gated cation channels.

Blindness↗
PubMed1996

Evidence for a fourth locus in Usher syndrome type I.

Usher syndrome type I (US1) is an autosomal recessive condition in which three different genes have been already localised (USH1A, USH1B, and USH1C on chromosomes 14q32, 11q13, and 11p15 respectively). The genetic heterogeneity of US1 has been confirmed in a previous study by linkage analysis of 20 French pedigrees. Here, we report the genetic exclusion of the three previously reported loci in two large multiplex families of Moroccan and Pakistani origin, suggesting the existence of at least a fourth locus in Usher syndrome type I.

Abnormalities, Multiple↗
PubMed1996

A single-center study of 11 patients with intraocular lymphoma treated with conventional chemotherapy followed by high-dose chemotherapy and autologous bone marrow transplantation in 5 cases.

Intraocular lymphoma (IOL) is a rare form of non Hodgkin lymphoma (NHL); it has a poor prognosis and is frequently associated with central nervous system (CNS) infiltration. We report the results of a prospective study of 11 patients with IOL who received conventional chemotherapy (CT), followed by salvage high-dose (HD) CT with autologous bone marrow transplantation (ABMT) in five cases. All 11 patients had abnormal funduscopic findings and six had CNS involvement at diagnosis. The diagnosis was based on vitrectomy in 10 cases and cerebral stereotaxic biopsy in one. Pathologic studies showed large-cell NHL in all cases. These large-cell NHL were of the B-cell type in 8 cases and of the T-cell type in two. First-line therapy consisted of a combination of cisplatin 25 mg/m2 as a 24-hour IV infusion on 4 consecutive days, VP-16 40 mg/m2 for 4 days, aracytine 2 g/m2 IV on day 5, and methylprednisolone 500 mg IV daily for 5 days (ESHAP) in 5 cases; alternating courses of ESHAP and HD methotrexate (MTX) in 4 cases; and HD MTX in 2 cases. Three patients underwent ocular and whole-brain radiation therapy. Five refractory patients subsequently received intensive CT with thiotepa 750 mg/m2, busulfan 10 mg/kg and cyclophosphamide 120 mg/kg, followed by ABMT. First-line treatment failed in 10 evaluable cases. One patient died of CNS progression at 12 months. All the patients who underwent intensive CT and ABMT entered CR; two relapsed at 6 months and three are alive in CR 15, 15 and 14 months after ABMT. Six patients are alive with persistent disease at 8, 13, 14, 15, 18 and 24 months. It seems in conclusion that, high-dose thiotepa, busulfan and cyclophosphamide followed by ABMT is effective in some cases of refractory IOL.

Aged↗
PubMed1996

[Rapid demonstration of mutations previously identified in parents at risk of patients with autosomic dominant retinitis pigmentosa].

PURPOSE: We have previously identified rhodopsin gene mutations in France in autosomal dominant (ADRP) retinitis pigmentosa in France, using a combination of SSCP (single-strand conformation polymorphism) and direct sequence analysis. The aim of this study was to perform a more rapid tool to identify a mutation in a ADRP family, when this mutation has been identified for one affected member of this family. METHODS: We looked for a restriction site, created or abolished by a mutation in the rhodopsin gene. We performed in vitro DNA amplification using PCR (polymerase chain reaction), enzymatic digestion, and migration on agarose gel. RESULTS: Abnormal patterns of migration were observed for affected ADRP members. DISCUSSION: This technique is useful and rapid (less than 5 hours) to recognize a previously identified mutation. However, previous precise identification of the mutation in one member of the family is needed.

DNA Restriction Enzymes↗
PubMed1996

[Chemodectoma secreting carotid glomus: characteristics and contribution of magnetic resonance imaging. Apropos of 2 cases].

Two cases of carotid glomus chemodectomas with production of catecholamines are reported. The place of chemodectomas among the neuroendocrine tumors called paragangliomas is recalled. Chemodectomas only very infrequently produce catecholamines (1 to 10%). Magnetic resonance imaging is superior to computerized tomography and metaiodobeuzylguanidine scintigraphy in the detection and the characterization of adrenal and extra-adrenal functioning paragangliomas of the orthosympathic system. Few data are available for the imaging of functioning parasympathetic paragangliomas (chemodectomas). The two case reports illustrate the contribution of the magnetic resonance imaging in the detection and the characterization of chemodectomas.

Adult↗