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Biomedical subjects

B Gross

Publications and source records attributed to B Gross.

At least 37 records · Page 2Linked to original sources
PubMed1999

Transcriptional activation of the cloned Heliothis virescens (Lepidoptera) ecdysone receptor (HvEcR) by muristeroneA.

Ecdysteroids play an important role during insect development. We report here the isolation and characterisation of an Ecdysone receptor (EcR) homologue from Heliothis virescens (HvEcR) and present evidence supporting the HvEcR active role as an active component of the native insect receptor. Alignment of the deduced amino acid sequence of HvEcR with those of EcRs from other species confirmed its membership of this family and showed that it is closely related to the B1 isoform of Drosophila melanogaster. Northern blot analysis showed that two transcripts (6.0 and 6.5 kb) were recognised by a probe spanning the DNA and ligand binding domains of the HvEcR. Genomic Southern blots showed that the HvEcR is encoded by a single copy gene. Two lines of evidence towards the functional activity of the HvEcR are presented. In vitro transcribed and translated HvEcR showed specific binding to hsp27 and pall response elements in the presence of CfUSP. Stable expression of HvEcR in 293 cells induced reporter gene activity in the presence of muristeroneA in a dose dependant manner while dexamethasone failed to activate.

ATP-Binding Cassette Transporters↗
PubMed1999

LAT is required for tyrosine phosphorylation of phospholipase cgamma2 and platelet activation by the collagen receptor GPVI.

In the present study, we have addressed the role of the linker for activation of T cells (LAT) in the regulation of phospholipase Cgamma2 (PLCgamma2) by the platelet collagen receptor glycoprotein VI (GPVI). LAT is tyrosine phosphorylated in human platelets heavily in response to collagen, collagen-related peptide (CRP), and FcgammaRIIA cross-linking but only weakly in response to the G-protein-receptor-coupled agonist thrombin. LAT tyrosine phosphorylation is abolished in CRP-stimulated Syk-deficient mouse platelets, whereas it is not altered in SLP-76-deficient mice or Btk-deficient X-linked agammaglobulinemia (XLA) human platelets. Using mice engineered to lack the adapter LAT, we showed that tyrosine phosphorylation of Syk and Btk in response to CRP was maintained in LAT-deficient platelets whereas phosphorylation of SLP-76 was slightly impaired. In contrast, tyrosine phosphorylation of PLCgamma2 was substantially reduced in LAT-deficient platelets but was not completely inhibited. The reduction in phosphorylation of PLCgamma2 was associated with marked inhibition of formation of phosphatidic acid, a metabolite of 1,2-diacylglycerol, phosphorylation of pleckstrin, a substrate of protein kinase C, and expression of P-selectin in response to CRP, whereas these parameters were not altered in response to thrombin. Activation of the fibrinogen receptor integrin alpha(IIb)beta(3) in response to CRP was also reduced in LAT-deficient platelets but was not completely inhibited. These results demonstrate that LAT tyrosine phosphorylation occurs downstream of Syk and is independent of the adapter SLP-76, and they establish a major role for LAT in the phosphorylation and activation of PLCgamma2, leading to downstream responses such as alpha-granule secretion and activation of integrin alpha(IIb)beta(3). The results further demonstrate that the major pathway of tyrosine phosphorylation of SLP-76 is independent of LAT and that there is a minor, LAT-independent pathway of tyrosine phosphorylation of PLCgamma2. We propose a model in which LAT and SLP-76 are required for PLCgamma2 phosphorylation but are regulated through independent pathways downstream of Syk.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice.

The adapter protein SLP-76 is expressed in T lymphocytes and hematopoietic cells of the myeloid lineage, and is known to be a substrate of the protein tyrosine kinases that are activated after ligation of the T-cell antigen receptor. Transient overexpression of SLP-76 in a T-cell line potentiates transcriptional activation after T-cell receptor ligation, while loss of SLP-76 expression abrogates several T-cell receptor-dependent signaling pathways. Mutant mice that lack SLP-76 manifest a severe block at an early stage of thymocyte development, implicating SLP-76 in signaling events that promote thymocyte maturation. While it is clear that SLP-76 plays a key role in development and activation of T lymphocytes, relatively little is understood regarding its role in transducing signals initiated after receptor ligation in other hematopoietic cell types. In this report, we describe fetal hemorrhage and perinatal mortality in SLP-76-deficient mice. Although megakaryocyte and platelet development proceeds normally in the absence of SLP-76, collagen-induced platelet aggregation and granule release is markedly impaired. Furthermore, treatment of SLP-76-deficient platelets with collagen fails to elicit tyrosine phosphorylation of phospholipase C-gamma2 (PLC-gamma2), suggesting that SLP-76 functions upstream of PLC-gamma2 activation. These data provide one potential mechanism for the fetal hemorrhage observed in SLP-76-deficient mice and reveal that SLP-76 expression is required for optimal receptor-mediated signal transduction in platelets as well as T lymphocytes.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Tryptophan toxicity--time and dose response in rats.

UNLABELLED: During the past decade L-tryptophan (Trp) ingestion have been associated with a multisystemic syndrome, known as eosinophilia myalgia syndrome (EMS). Even though an epidemic studies indicated that a contaminant, 1,1'-ethylidene-bis-L-tryptophan was involved in EMS, abnormalities in metabolism of Trp have been reported in other similar clinical syndromes such as carcinoid syndrome, scleroderma or eosinophilic fasciitis. The purpose of the study was to investigate the role of Trp or its metabolite, given in different dosing regimens in induction of tissue damage. METHOD: 3 months old female rats (Charles River CD-1) were fed for 3, 6, 12 weeks on a diet containing 20% protein diet derived from casein and supplemented with 1%, 2%, or 5% Trp. On the last week of feeding, half of the animals fed on a control diet and half of the animals fed on the Trp diet were injected with 2 injections of para-chlorophenyl alanine (p-CPA), a Trp hydroxylase inhibitor, 300 mg/kg i.p. followed by 3 injection of 100 mg/kg every alternate day. RESULTS: Body weight of rats fed higher levels of Trp increased slowly and injection of p-CPA induced loss in body weight. 2/6 of the animals treated with 1% Trp and 1/6 treated with 5% Trp for 3 weeks and 2/4 animals treated with 1% Trp and 1/4 treated with 5% Trp for 12 weeks died after injection of p-CPA. No mortality was detected in 1-5% Trp treated animals. Alopecia and skin changes were seen after p-CPA in 1-5% Trp treated animals. Increased amounts of connective tissue and induction of inflammatory cell proliferation were observed in lung, spleen and in gastrocnemia muscle of rats treated with higher dose of Trp for longer period. Induction of kynurenine pathway by injection of p-CPA caused more tissue damage. It is concluded that excessive Trp or elevation of its metabolites could play a role in amplifying some of pathological features of EMS. This pathological damage is further augmented by metabolites of the kynurenine pathway.

Alopecia↗
PubMed1998

The Weyl character formula, the half-spin representations, and equal rank subgroups.

Let B be a reductive Lie subalgebra of a semi-simple Lie algebra F of the same rank both over the complex numbers. To each finite dimensional irreducible representation Vlambda of F we assign a multiplet of irreducible representations of B with m elements in each multiplet, where m is the index of the Weyl group of B in the Weyl group of F. We obtain a generalization of the Weyl character formula; our formula gives the character of Vlambda as a quotient whose numerator is an alternating sum of the characters in the multiplet associated to Vlambda and whose denominator is an alternating sum of the characters of the multiplet associated to the trivial representation of F.

Journal Article↗
PubMed1998

Clinical significance of echogenic amniotic fluid.

PURPOSE: This study aimed to determine the clinical significance of echogenic amniotic fluid. METHODS: We prospectively studied 19 twin pregnancies in which the amniotic fluid in 1 sac was anechoic and that in the other sac was echogenic. Morphologic characteristics of amniotic fluid were assessed from samples taken at amniocentesis or upon delivery within 48 hours after sonographic examination. RESULTS: In twins with echogenic amniotic fluid, assessment revealed clear fluid in 6 cases (32%), vernix caseosa in 12 (63%), and meconium in 1 (5%). In co-twins with anechoic amniotic fluid, assessment revealed clear fluid in 9 cases (47%), vernix caseosa in 6 (32%), and meconium in 4 (21%). CONCLUSIONS: Echogenic amniotic fluid on prenatal sonography is not predictive of meconium.

Adult↗
PubMed1998

Cephalhematoma and caput succedaneum: do they always occur in labor?

OBJECTIVE: Our purpose was to analyze our experience with cephalhematomas detected prenatally by ultrasonography. STUDY DESIGN: Seven cases of cephalhematomas were identified prenatally among 16,292 fetuses having comprehensive ultrasonographic examinations between 1993 and 1996. The course of pregnancy and the neonatal outcome were reviewed in each case. RESULTS: Cephalhematomas appeared as an echogenic bulge posterior to the occipital region (5 cases) or at the temporal region of the fetal head (2 cases). CONCLUSION: Cephalhematomas, which are believed to be a result of operative delivery, can also originate, in utero, antepartum. Premature rupture of membranes appears to be an associated factor.

Birth Injuries↗
PubMed1997

Basolateral localization and transcytosis of gonadotropin and thyrotropin receptors expressed in Madin-Darby canine kidney cells.

The thyrotropin (TSH) and follicle-stimulating hormone (FSH) receptors are present mainly on the basolateral cell surface in the thyroid gland and in Sertoli cells, whereas in ovarian and in testicular cells, the luteinizing hormone (LH) receptors are distributed throughout the cell surface. When expressed in Madin-Darby canine kidney (MDCK) cells, all three receptors accumulated at the basolateral cell surface showing that they carry the corresponding targeting signals. The receptors were directly delivered to the basolateral surface of the MDCK cells. A minor fraction of the gonadotropin receptors but not of TSH receptors was secondarily targeted to the apical surface through transcytosis. The mechanisms of basolateral targeting and transcytosis were analyzed using the FSH receptor as a model. Both were insensitive to brefeldin A and pertussis toxin. Gs activation by AlF4- and cholera toxin provoked a marked enhancement of FSH receptor transcytosis. The population of Gs proteins involved in this mechanism was different from that involved in signal transduction since neither FSH nor forskolin mimicked the effects of AlF4- and cholera toxin. Gs activation provoked a similar effect on LH receptor distribution in MDCK cells, whereas it did not modify the compartmentalization of the TSH receptor. Hormone-specific transcytosis was observed in MDCK cells expressing the gonadotropin (FSH and LH) receptors and was increased after cholera toxin administration.

Animals↗
PubMed1997

Prediction of fetal macrosomia using sonographically measured abdominal subcutaneous tissue thickness.

PURPOSE: We assessed the usefulness of sonographic measurement of abdominal subcutaneous tissue thickness in predicting fetal macrosomia (weight > 4,000 g). METHODS: Abdominal subcutaneous tissue thickness was measured sonographically in 133 term fetuses. All studied fetuses were delivered within 72 hours after the measurements were taken. RESULTS: One hundred thirteen fetuses were normal size, and 20 were macrosomic. The fetal abdominal subcutaneous tissue thickness ranged between 3 and 18 mm in all fetuses, with a mean measurement of 8.4 +/- 2.7 mm (standard deviation). The mean tissue thickness differed significantly between normal and macrosomic fetuses (7.0 mm versus 12.4 mm, respectively; p < 0.0001). There was a significant positive correlation between the abdominal subcutaneous tissue thickness and the birth weight (r = 0.67, p < 0.0001). The negative predictive value for a range of cut-off points between 8 and 13 mm varied between 84.3% and 100% (for prevalence rates of macrosomia of 5-25%). However, the positive predictive value was less than 50% for cut-off values below 11 mm. CONCLUSIONS: Sonographic measurement of the subcutaneous tissue thickness of the fetal abdomen is useful for ruling out macrosomia.

Abdominal Muscles↗
PubMed1997

Coronary implantation of silicone-carbide-coated Palmaz-Schatz stents in patients with high risk of stent thrombosis without oral anticoagulation.

Coronary stenting in bail-out situations is effective but associated with increased stent thrombosis and bleeding rates. Silicone-carbide coating reduces fibrinogen activation on alloplastic surfaces and thus may also reduce stent thromboses. A total of 44 patients received 58 silicone-carbide-coated stents for threatened (80%) or abrupt (20%) closure. In addition to heparin, patients were treated with aspirin and ticlopidine (75%) or aspirin (25%) only. Two patients (4.5%) died in the hospital. The combined in-hospital complication rate including death, emergency revascularization, stent-related myocardial infarction, and stent thrombosis was 9% (4 of 44 patients). Major bleeding occurred in 4 patients (9%). Six-month follow-up angiography was obtained in all eligible patients (42 of 44), revealing a restenosis rate of 21% (9 of 42). Thus, coronary implantation of silicone-carbide-coated stents is feasible in bail-out situations without oral anticoagulation and with a low complication rate. Further studies are required to optimize the anticoagulation regimen with this type of coating.

Adult↗
PubMed1997

Prenatal diagnosis of pseudothalidomide syndrome in consecutive pregnancies of a consanguineous couple.

Pseudothalidomide syndrome is a rare autosomal recessive condition characterized by tetraphocomelia, craniofacial abnormalities and postnatal growth restriction. We report the prenatal sonographic findings of pseudothalidomide syndrome in three consecutive pregnancies of a consanguineous couple. In the last pregnancy, the correct diagnosis was made sonographically at 11 weeks of pregnancy. The combination of transabdominal and transvaginal ultrasound examinations revealed a large cystic hygroma extending over the lower back. The lower extremities were markedly shortened with no identifiable bones below the level of the femora. The humeri on both sides were shortened; ulnae were small with no identifiable radii. The pregnancy was terminated by dilatation and curettage and diagnosis confirmed at 12 weeks of pregnancy. In conclusion, fetuses with pseudothalidomide syndrome may exhibit characteristic findings in the first trimester of pregnancy which can be detected using ultrasound.

Abnormalities, Multiple↗
PubMed1997

Jugular venous blood flow velocity waveforms in human fetuses between 20 and 42 weeks of pregnancy.

BACKGROUND: The goal of the study was to measure the blood flow parameters of the fetal internal jugular vein during the second half of normal pregnancy using Doppler ultrasound. METHODS: Jugular blood flow was analyzed in 95 normal singleton fetuses between 20 and 42 weeks gestation. Color and pulsed Doppler ultrasound was used to obtain jugular venous waveforms at the level of the mid-neck. Peak velocities, ratios of velocities, and time-averaged maximum velocities were measured. RESULTS: Jugular venous waveforms in healthy fetuses consist of three phases--the first forward peak occurs during ventricle systole; the second forward peak occurs during early diastole and the third peak occurs during atrial contraction. Forty-eight percent of the fetuses demonstrated absent flow during atrial contraction; 32% of fetuses demonstrated forward flow during atrial contraction and finally 20% of fetuses demonstrated flow reversal during atrial contraction. CONCLUSIONS: The reported jugular venous profile may serve as a foundation for future studies of jugular blood flow in high risk fetuses.

Adult↗
PubMed1996

[Drug-induced hepatic involvement, something to consider!].

A retrospective study over the last 5 years on drug-induced liver injury was performed in the Internal Medicine Department of the University Hospital of Geneva. According to WHO and Council for International Organizations of Medical Sciences (CIOMS) criteria for drug-induced liver adverse events, 142 cases were identified, with 255 drugs fulfilling causality criteria of certain, probable or possible. 63 patients (44%) suffered severe consequences of liver injury, including 9 deaths. Drugs reported belonged to the therapeutic classes of antibiotics (43%), cardiovascular (20%), analgesics (10%), gastrointestinal (9%), psychotropic (7%), and others (11%). Despite bias inherent to the retrospective methodology, only 10% of the side effects were spontaneously reported to the pharmaco-vigilance board. This is in accordance with the known reporting rate. It can be concluded that spontaneous reports are to be regarded only as signals.

Adult↗
PubMed1996

Fetal pharyngeal distention--is it a normal component of fetal swallowing?

Fetal swallowing is one of the main mechanisms of amniotic fluid circulation. Swallowing mechanisms were studied in 34 healthy fetuses using modern ultrasound technology. The fetal lips and mouth, as well as tongue, pharynx, larynx, trachea and esophagus were surveyed in serial sagittal planes. Fetal swallowing movements were recorded and subsequently analyzed from the videotapes. All neonates were born at term in a satisfactory condition. Twenty-nine infants were breastfed, and five were bottle fed. No feeding problems were reported in these neonates. In 85% of fetuses, swallowing activity started with suckling movements followed by wide opening of the mouth. Next, low frequency tongue movements propelled the fluid bolus into the hypopharynx. In 15% of fetuses, this activity was associated with prolonged pharyngeal dilatation. Prolonged pharyngeal dilatation does not signify fetal neurological compromise as judged by good neonatal outcome and probably represents a normal variant of fetal swallowing.

Amniotic Fluid↗
PubMed1996

Microsatellites and PCR primers for genetic studies and genomic sequencing of the human TSH receptor gene.

The thyroid stimulating hormone receptor (TSHR) is the main autoantigen in Graves' disease. Mutations of the TSH receptor have been implicated in various thyroid diseases. In this study, we describe three polymorphic markers localised within introns 2 and 7 of the TSH receptor gene. These markers are useful for the study of genetic diseases involving the TSH receptor. They allowed us to map precisely the TSH receptor gene on chromosome 14q31 between D14S287 and D14S68. We also describe selected primers and experimental conditions for the amplification and direct genomic sequencing of the 10 exons of the receptor gene.

Base Sequence↗
PubMed1996

Prenatal diagnosis of an aneurysm of the right atrium.

Congenital aneurysm of the right atrium was diagnosed in a 17-week fetus. It appeared as an outward bulge of the right atrium which doubled its size. The aneurysm was akinetic. Flow across the atrioventricular valves appeared unobstructed. The fetus had no evidence of cardiac failure. The patient elected to terminate the pregnancy. Autopsy results were confirmatory.

Adult↗