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S Gerber

Publications and source records attributed to S Gerber.

At least 37 records · Page 2Linked to original sources
PubMed2001

Lipopolysaccharide stimulation of 70 kilo Dalton heat shock protein messenger ribonucleic acid production in cultured human fetal membranes.

OBJECTIVE: The 70 kilo Dalton heat shock protein is up-regulated when cells are under physiological stress. It prevents protein denaturation and incorrect polypeptide assembly, and inhibits apoptosis as well as the transcription of genes coding for pro-inflammatory cytokines. To evaluate if up-regulation of heat shock protein 70 can occur during pregnancy, we examined whether addition of bacterial lipopolysaccharide to human amniochorion membranes in vitro stimulated heat shock protein 70 gene transcription. MATERIALS AND METHODS: Amniochorionic membranes (n = 5), collected at the time of elective repeat cesarean section prior to labor from normal term gestations, were placed in an organ explant system. After 48 hour in culture, the membranes were stimulated with lipopolysaccharide for 24 hours. Total RNA was extracted and subjected to an oligo dT primed reverse transcriptase reaction followed by polymerase chain reaction (PCR) using heat shock protein 70 specific primers. PCR products were hybridized with biotinylated internal probes and identified by enzyme-linked immunosorbent assay (ELISA). Results were analyzed by Mann-Whitney U test. A p < 0.05 was significant. RESULTS: Heat shock protein 70 messenger RNA was expressed by all fetal membrane preparations both prior to and following in vitro culture. Addition of lipopolysaccharide increased the concentrations of heat shock protein 70 messenger RNA in each sample tested from a mean of 35.5 +/- 29.6 ng/milliliter (12.1-80.1 ng/milliliter) to 169.6 +/- 69.9 ng/ml (51.7-218.2 ng/milliliter) (p = 0.03). CONCLUSION: Human fetal membranes constitutively express heat shock protein 70 messenger ribonucleic acid. Bacterial lipopolysaccharide markedly stimulated heat shock protein 70 messenger RNA gene transcription in human fetal membranes. Thus, heat shock protein 70 is inducible in fetal membranes and may facilitate fetal survival under adverse conditions.

Cesarean Section↗
PubMed2001

Complete abolition of the retinal-specific guanylyl cyclase (retGC-1) catalytic ability consistently leads to leber congenital amaurosis (LCA).

PURPOSE: Leber congenital amaurosis (LCA) is the earliest and the most severe form of all inherited retinal dystrophies. In 1996, the current investigators ascribed the disease in families linked to the LCA1 locus on chromosome 17p13.1 to mutations in the photoreceptor-specific guanylyl cyclase (retGC-1) gene. So far, 22 different mutations, of which 11 are missense mutations, have been identified in 25 unrelated families. This is a report of the functional analyses of nine of the missense mutations. METHODS: cDNA constructs were generated that contained the retGC-1 missense mutations identified in patients related to the LCA1 locus. Mutants were expressed in COS7 cells and assayed for their ability to hydrolyze guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP). RESULTS: All mutations lying in the catalytic domain showed a complete abolition of cyclase activity. In contrast, only one mutation lying in the extracellular domain also resulted in a severely reduced catalytic activity, whereas the others showed completely normal activity. CONCLUSIONS: More than half the mutations identified in patients related to the LCA1 locus are truncating mutations expected to result in a total abolition of retGC-1 activity. Concerning missense mutations, half of them lying in the catalytic domain of the protein also result in the complete inability of the mutant cyclases to hydrolyze GTP into cGMP in vitro. In contrast, missense mutations lying in the extracellular domain, except one affecting the initiation codon, showed normal catalytic activity of retGC-1. Nevertheless, considering that all patients related to the LCA1 locus displayed the same phenotype, it can be assumed that all missense mutations would have the same dramatic consequences on protein activity in vivo as truncation mutations.

Animals↗
PubMed2000

[Laparoscopic transabdominal preperitoneal hernioplasty. Evaluation of complications due to transabdominal approach].

INTRODUCTION: Since the introduction of laparoscopic hernioplasty the TAPP procedure (transabdominal preperitoneal approach) has become the most widely used technique. Many surgeons have changed to the total extraperitoneal approach (TEP), because they fear the consequences of a peritoneal lesion. METHOD: We evaluated our results with TAPP in a retrospective study, with special attention to complications caused by the approach. We operated on 460 hernias in 390 patients in a period of 5 years. RESULTS: Complication rates and recurrence rates were similar to those after TEP. There was a marked learning curve with decrease of both rates during the evaluated years. There were no complications related to the transabdominal approach other than trocar hernias, the rate of which could be reduced by eliminating the learning curve and by using smaller trocar diameter. CONCLUSION: We see no reason to change from TAPP to the TEP technique.

Adult↗
PubMed2000

[Paratesticular sarcomas. Case report of leiomyosarcoma].

Paratesticular sarcomas are rare. We discuss this entity with the aid of a case report and the existing literature. The therapy of these tumors includes resection and possible adjuvant radiotherapy. Rhabdomyosarcomas are an exception, because they also show a good response to chemotherapy.

Diagnosis, Differential↗
PubMed2000

The photoreceptor cell-specific nuclear receptor gene (PNR) accounts for retinitis pigmentosa in the Crypto-Jews from Portugal (Marranos), survivors from the Spanish Inquisition.

The last Crypto-Jews (Marranos) are the survivors of Spanish Jews who were persecuted in the late fifteenth century, escaped to Portugal and were forced to convert to save their lives. Isolated groups still exist in mountainous areas such as Belmonte in the Beira-Baixa province of Portugal. We report here the genetic study of a highly consanguineous endogamic population of Crypto-Jews of Belmonte affected with autosomal recessive retinitis pigmentosa (RP). A genome-wide search for homozygosity allowed us to localize the disease gene to chromosome 15q22-q24 (Zmax=2.95 at theta=0 at the D15S131 locus). Interestingly, the photoreceptor cell-specific nuclear receptor (PNR) gene, the expression of which is restricted to the outer nuclear layer of retinal photoreceptor cells, was found to map to the YAC contig encompassing the disease locus. A search for mutations allowed us to ascribe the RP of Crypto-Jews of Belmonte to a homozygous missense mutation in the PNR gene. Preliminary haplotype studies support the view that this mutation is relatively ancient but probably occurred after the population settled in Belmonte.

Chromosomes, Human, Pair 15↗
PubMed2000

The morcellator knife: a new laparoscopic instrument for supracervical hysterectomy and morcellation.

BACKGROUND: Cutting the cervix, morcellation, and extraction of the uterus and myomata remain major problems in endoscopic surgery. We developed an efficient, safe, reusable, and inexpensive instrument to cut the cervix and morcellate the uterus and myomata: the morcellator knife. INSTRUMENT: The morcellator knife is a classic lancet with an interchangeable blade, transformed into an endoscopic instrument that can be inserted easily through a 10-mm-diameter trocar. The blade has an automatic retraction system and is set in the standby position, ensuring security. Cutting the cervix and uterine or myoma fragmentation are easy. The mass to be cut is held between two grasping forceps for easy cutting with the blade, under permanent visual control. After morcellation, extraction of the masses is performed through a posterior culdotomy. EXPERIENCE: We have used this morcellator knife in 54 subtotal hysterectomies and 16 myomectomies. There were no complications during the procedures. Morcellation lasted 3-14 minutes and involved the use of an average of two to three blades. CONCLUSION: The morcellator knife is a simple, safe, reusable, and inexpensive instrument with a low maintenance cost.

Female↗
PubMed2000

Surgical therapy of juxtapapillary tumors.

INTRODUCTION: Tumors of the papilla of Vater represent a pathophysiological entity. We propose a precise definition of these tumors and give a summary of diagnostics and therapy as well as a review of the literature. DEFINITION, SYMPTOMS, THERAPY: The most accurate definition includes all tumors originating within one cm of the papilla, regardless of their histology. We therefore use the term of "juxtapapillary tumors". Early symptoms are itching, jaundice, sometimes pain and cholangitis/cholecystitis. The first diagnostic means are sonography, CT-scan, ERCP and angiography. The therapeutic options range from pure palliation by stenting or bypass surgery with the specific option of transduodenal local tumor excision to the curative intention of a radical pylorus preserving duodenopancreatectomy (Whipple resection). PROGNOSIS, RESULTS: Prognostic factors include growth pattern, histology, stage and lymph node involvement of the tumor. Another, new method with prognostic value seems to be the DNA-fingerprinting. A literature review of the different therapeutic modalities shows the following results: After stenting, the median survival is 10 months. The median 5-year survival after local excision and radical resection lies between 30-50%, with huge differences according to tumor stage. CONCLUSIONS: With a strict definition, more precise guide-lines concerning the therapy of such tumors seem adequate. These depend on tumor stage and dignity, general health condition of the patient and experience of the institution. Considering the low perioperative mortality of radical resection (actually below 5%), there will be increasing indications for this option in the future. But nevertheless, there are good palliative alternatives for selected cases.

Ampulla of Vater↗
PubMed2000

Preparation and analysis of fetal liver extracts.

The aim of this work is to describe the techniques that have been used for preparation and analysis of whole fetal liver extracts destined for in utero transplantation. Nine fetal livers between 12 and 17 weeks of gestation were prepared: cell counts and assessment of the hematopoietic cell viability were performed on cell suspensions. Hepatocytes represented 40 to 80% of the whole cell population. The remaining cells were constituted by hematopoietic cells (mainly erythroblasts), as well as by endothelial cells. The latter expressed CD34 on their surface, interfering with the assessment of CD34+ hematopoietic cells by flow cytometry. Direct visual morphologic control using alkaline phosphatase anti-alkaline phosphatase techniques was needed to differentiate hematopoietic from extra-hematopoietic CD34+ cells. Between 3.0 and 34.6 x 10(6) CD34+ viable hematopoietic cells were collected per fetal liver. Adequate differentiation of these cells into burst-forming units erythroid (BFU-E), colony-forming units granulocyte-macrophage (CFU-GM), and colony-forming units granulocyte erythroid macrophage megakaryocyte (CFU-GEMM) has been shown for each sample in clonogeneic cultures. In conclusion, fetal liver is a potential source of hematopoietic stem cells. Their numeration, based on the presence of CD34, is hampered by the expression of this antigen on other cells contained in the liver cell extract, in particular endothelial cells.

Antigens, CD34↗
PubMed2000

Spectrum of retGC1 mutations in Leber's congenital amaurosis.

Leber's congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies responsible for congenital blindness. Genetic heterogeneity of LCA has been suspected since the report by Waardenburg of normal children born to affected parents. In 1995 we localised the first disease causing gene, LCA1, to chromosome 17p13 and confirmed the genetic heterogeneity. In 1996 we ascribed LCA1 to mutations in the photoreceptor-specific guanylate cyclase gene (retGC1). Here, we report on the screening of the whole coding sequence of the retGC1 gene in 118 patients affected with LCA. We found 22 different mutations in 24 unrelated families originating from various countries of the world. It is worth noting that all retGC1 mutations consistently caused congenital cone-rod dystrophy in our series, confirming the previous genotype-phenotype correlations we were able to establish. RetGC1 is an essential protein implicated in the phototransduction cascade, especially in the recovery of the dark state after the excitation process of photoreceptor cells by light stimulation. We postulate that the retGC1 mutations hinder the restoration of the basal level of cGMP of cone and rod photoreceptor cells, leading to a situation equivalent to consistent light exposure during photoreceptor development, explaining the severity of the visual disorder at birth.

Blindness↗
PubMed2000

Comparison of microsatellites and amplified fragment length polymorphism markers for parentage analysis.

This study compares the properties of dominant markers, such as amplified fragment length polymorphisms (AFLPs), with those of codominant multiallelic markers, such as microsatellites, in reconstructing parentage. These two types of markers were used to search for both parents of an individual without prior knowledge of their relationships, by calculating likelihood ratios based on genotypic data, including mistyping. Experimental data on 89 oak trees genotyped for six microsatellite markers and 159 polymorphic AFLP loci were used as a starting point for simulations and tests. Both sets of markers produced high exclusion probabilities, and among dominant markers those with dominant allele frequencies in the range 0.1-0.4 were more informative. Such codominant and dominant markers can be used to construct powerful statistical tests to decide whether a genotyped individual (or two individuals) can be considered as the true parent (or parent pair). Gene flow from outside the study stand (GFO), inferred from parentage analysis with microsatellites, overestimated the true GFO, whereas with AFLPs it was underestimated. As expected, dominant markers are less efficient than codominant markers for achieving this, but can still be used with good confidence, especially when loci are deliberately selected according to their allele frequencies.

DNA, Plant↗
PubMed2000

Ocular and central nervous system lymphoma: clinical features and diagnosis.

PURPOSE: To evaluate the clinical, angiographic, and cytopathologic features of ocular and central nervous system (CNS) lymphoma. PATIENTS AND METHODS: Retrospective study of 44 patients over a 10-year period. RESULTS: A total of 36 women and six men, mean age 54 years (range: 36-90 years), were included. The mean time interval between onset of ocular symptoms and diagnosis was 40 months (range: 1-144 months). Ocular involvement was bilateral in 84% of the cases. Laser flare photometry readings averaged 9.6 photons/ms (2.9-78.3 photons/ms). Vitritis was constant. Funduscopy revealed RPE abnormalities in 60.49% of the cases and punctuate retinal infiltrates in 33.5%. The most common findings with fluorescein angiography were window defects and hypofluorescent round lesions. Patients had CNS involvement in 66% of the cases. Cytologic examination of the vitreous samples showed high-grade B lymphoma in 86% of the cases. Interleukin-10 dosage, when performed, showed elevated levels averaging 2352 pg/ml in all vitreous samples. Molecular biology based on PCR confirmed the diagnosis in 12 patients. Treatment included systemic chemotherapy alone or associated with radiotherapy in various regimens. Fourteen patients died during follow-up. Only 12 patients were in complete remission. CONCLUSION: The prognosis of the disease remains poor. However, the new diagnostic tools and therapeutic strategies may improve the diagnostic delay and the survival outcome.

Adult↗
PubMed2000

Quantitative trait loci: a meta-analysis.

This article presents a method to combine QTL results from different independent analyses. This method provides a modified Akaike criterion that can be used to decide how many QTL are actually represented by the QTL detected in different experiments. This criterion is computed to choose between models with one, two, three, etc., QTL. Simulations are carried out to investigate the quality of the model obtained with this method in various situations. It appears that the method allows the length of the confidence interval of QTL location to be consistently reduced when there are only very few "actual" QTL locations. An application of the method is given using data from the maize database available online at http://www. agron.missouri.edu/.

Databases, Factual↗
PubMed2000

ABCR gene analysis in familial exudative age-related macular degeneration.

PURPOSE: Identification of genetic factors in the pathogenesis of age-related macular degeneration (AMD) is of crucial importance in this common cause of blindness. Mutations in the Stargardt disease gene (ABCR) were previously reported in patients with atrophic forms of AMD. The purpose of this study was to analyze familial segregation of ABCR gene mutations in 52 unrelated multiplex cases of exudative AMD. METHODS: A complete ophthalmological examination including visual acuity measurement, fundus examination, and fluorescein angiography (FA) was performed on each exudative AMD patient. The entire coding sequence of the ABCR gene was analyzed using a combination of single-strand conformation polymorphism and confirmatory sequencing of the exons showing an abnormal pattern of migration. RESULTS: Six heterozygous missense changes were identified. A lack of familial segregation was observed in 4 of 6 codon changes (Arg943Gln, Val1433Ile, Pro1948Leu, and Ser2255Ile). Conversely, 2 codon changes cosegregated with the disease in 2 small families: Pro940Arg and Leu1970Phe. CONCLUSIONS: The authors believe that segregation of the ABCR gene mutations with familial cases of AMD has not yet been shown. The analysis of familial segregation allowed the authors to exclude 4 of 6 codon changes as disease-causing mutations. Furthermore, it was shown here that the ABCR gene may be rarely involved in exudative AMD, with at best 2 of 52 familial cases (4%) related to this susceptibility factor.

ATP-Binding Cassette Transporters↗
PubMed1999

Leber congenital amaurosis.

Leber's congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies responsible for congenital blindness. Genetic heterogeneity of LCA has been suspected since the report by Waardenburg of normal children born to affected parents. In 1995, we localized the first disease causing gene, LCA1, to chromosome 17p13 and confirmed the genetic heterogeneity. In 1996, we ascribed LCA1 to mutations in the photoreceptor-specific guanylate cyclase gene (retGC1). RetGC1 is an essential protein implicated in the phototransduction cascade, especially in the recovery of the dark state after the excitation process of photoreceptor cells by light stimulation. In 1997, mutations in a second gene were reported in LCA, the RPE65 gene, which is the first specific retinal pigment epithelium gene. The protein RPE65 is implicated in the metabolism of vitamin A, the precursor of the photoexcitable retinal pigment (rhodopsin). Finally, a third gene, CRX, implicated in photoreceptor development, has been suspected of causing a few cases of LCA. Taken together, these three genes account for only 27% of LCA cases in our series. The three genes encode proteins that are involved in completely different physiopathologic pathways. Based on these striking differences of physiopathologic processes, we reexamined all clinical physiopathological discrepancies and the results strongly suggested that retGC1 gene mutations are responsible for congenital stationary severe cone-rod dystrophy, while RPE65 gene mutations are responsible for congenital severe but progressive rod-cone dystrophy. It is of tremendous importance to confirm and to refine these genotype-phenotype correlations on a large scale in order to anticipate the final outcome in a blind infant, on the one hand, and to further guide genetic studies in older patients on the other hand.

Animals↗
PubMed1999

Age-related macular degeneration in grandparents of patients with Stargardt disease: genetic study.

PURPOSE: To report clinical features and molecular genetic study in three unrelated families in which age-related macular degeneration was observed in grandparents of patients with Stargardt disease. METHODS: A complete ophthalmologic examination including best-corrected visual acuity measurement, fundus examination, and fluorescein angiography was performed on all members of the three families. The entire coding sequence of the ABCR gene was analyzed using a combination of single strand conformation polymorphism and direct sequence analysis of the 50 exons. RESULTS: Compound heterozygous missense mutations were observed in patients with Stargardt disease (Arg212Cys, Argl107Cys, Gly1977Ser, Arg2107His, and le2113Met). Heterozygous missense mutations were observed in the grandparents with age-related macular degeneration (Arg212Cys and Arg1107Cys). CONCLUSIONS: We report phenotype and genotype findings in three unrelated families segregating patients with Stargardt disease and age-related macular degeneration. The hypothesis that the Arg212Cys and Arg1107Cys ABCR gene mutations could be susceptibility factors for age-related macular degeneration is discussed. We speculate that the relatives of patients affected with Stargardt disease who are carriers of heterozygous ABCR gene mutations may have a higher risk of developing age-related macular degeneration.

ATP-Binding Cassette Transporters↗
PubMed1999

A comparison of forearm and thumb muscle electromyographic responses to the use of laparoscopic instruments with either a finger grasp or a palm grasp.

Laparoscopic techniques allow for less-invasive treatment of common surgical problems. Laparoscopic instruments are different from standard surgical instruments and generally incorporate a pistol-grip handle configuration with rings for the fingers. This handle configuration has been reported as being uncomfortable, leading to finger compression neuropathies in some cases. As an alternative, the surgeon can choose to grasp laparoscopic instruments using a more powerful palm grip during grasping motions. This study evaluates the hypothesis that the use of the palm grip requires less muscle tension than the finger-grip when grasping with laparoscopic instruments. Nine general surgeons used an Autosuture laparoscopic grasper with a ringed pistol-grip handle held in both a finger-in-ring (F) or palm (P) hand grip position to grasp and close two spring-loaded metal plates. The same task was performed with a surgical haemostat clamp (H) for comparison. Each subject performed the grasping task in a random sequence for the three instrument configurations at two grasping forces levels (0.7 and 4.2 N), and with the instrument at three angles to the subjects' sagittal plane (0 degree, 45 degrees and 90 degrees). Surface electromyographic (EMG) signals were acquired from the flexor carpi ulnaris (FCU), flexor digitorum profundus (FDP), flexor digitorum superficialis (FDS), extensor carpi ulnaris (ECU), extensor digitorum comunis (EDC) and the thenar compartment (TH). The peak root mean squared (RMS) EMG voltage was averaged for five repetitions at each instrument, force and angle condition. Statistical analysis was carried out by repeated measures ANOVA. The muscle EMG RMS amplitude while using the palm grip was decreased in the FDS, TH and EDC, was unchanged in the ECU and FCU, and was slightly higher in the FDP when compared with the finger grip. These differences were most prominent at 90 degrees to the sagittal plane where the subjects' wrists neared maximal flexion. It is concluded that the palm grip is more powerful than the finger grip when grasping with laparoscopic instruments, particularly at angles perpendicular to the surgeon's sagittal plane.

Electromyography↗