Search PubMed⌕ Search

Biomedical subjects

M Baron

Publications and source records attributed to M Baron.

At least 109 records · Page 6Linked to original sources
PubMed1994

A pedigree series for mapping disease genes in bipolar affective disorder: sampling, assessment, and analytic considerations.

A series of 57 extended pedigrees with high density of bipolar affective disorder is described. Ascertainment and diagnostic procedures are documented and simulation studies to assess statistical power are carried out. The pedigrees, obtained in the US and Israel, are comprised of 1508 adult individuals with best estimate consensus diagnoses (12-71 relatives per pedigree), 490 of whom (including 401 sib pairs) meet criteria for a conservative disease definition (bipolar disorder or recurrent major depression). Cell lines have been established on 1324 of these individuals. Statistical power to detect linkage with lod score analysis, assuming autosomal dominant transmission and highly polymorphic DNA markers, is nearly 100% for alpha (proportion of linked families) = 30%, and 75% for alpha = 20%. This is the largest bipolar pedigree series reported to date; its unique features make it amenable to various gene detection techniques.

Bipolar Disorder↗
PubMed1993

Secondary structure of a pair of fibronectin type 1 modules by two-dimensional nuclear magnetic resonance.

The fourth and fifth type 1 module pair, corresponding to residues 151-244 from the amino terminus of human fibronectin, has been produced as a recombinant protein using a yeast expression system and studied by two-dimensional homonuclear 1H nuclear magnetic resonance (NMR) spectroscopy. The sequence-specific resonance assignment of the 1H NMR spectrum has been completed using a combination of 2D 1H nuclear Overhauser effect (NOE) spectroscopy, homonuclear Hartmann-Hahn, and correlated spectroscopy spectra recorded under a variety of pH and temperature conditions. Slow exchanging amide protons have been identified and estimates of many backbone 3JNH-C alpha H coupling constants were obtained by line shape fitting. The secondary structures of each module conform closely to the "consensus" fibronectin type 1 module structure determined previously for two other single type 1 modules. In the module pair described here, the two modules are linked by a short five-residue linker which appears to form a turn. The intermodule interface is defined by NOEs observed between a hydrophobic three-residue sequence from the fourth type 1 module and residues in the first double-stranded beta-sheet of the fifth type 1 module. The interaction is dominated by a tryptophan residue (unconserved in other type 1 sequences) within the fourth module, which causes large upfield ring current shifts for several proton resonances from the beta-sheet of the fifth module. The NMR data indicate that there is little or no relative reorientation of the two modules about the linker region but rather that the two modules combine with a fixed and intimate hydrophobic contact.

Amino Acid Sequence↗
PubMed1993

Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees.

The hypothesis that chromosomal region Xq27-28 harbours a gene for manic-depression has been a focus of interest in human genetics. X-linked inheritance of manic depressive illness has been re-examined in 3 multigeneration Israeli kindreds. Extension and re-evaluation of pedigree data, including new individuals, diagnostic follow-up, and analysis with DNA markers, shows greatly diminished support for linkage to Xq28. The peak lod scores in two of the pedigrees have dropped several lod units to clearly negative values at the RCP-F8-G6PD gene cluster. On the other hand, positive lod scores (Zmax = 2.09) are sustained in another pedigree at the same map location. None of the pedigrees show linkage to more proximal markers, including the Xq27 locus DXS98. Our analysis underscores the uncertainties in studying complex disorders.

Adult↗
PubMed1993

Laparoscopy in adnexal pathology in the child: a study of 28 cases.

We report our experience with laparoscopy in adnexal pathology in the child. Twenty-eight children (mean age 13 years; range 8 to 16) underwent 30 laparoscopy procedures. Therapeutic laparoscopy was performed in 3 cases: transposition of an ovary before radiotherapy, bilateral gonadal excision for Turner's syndrome and ovarian fixation after contralateral torsion of normal adnexa (TNA). Diagnostic and potentially therapeutic laparoscopy was performed in 25 cases: 12 suspected torsion of adnexa (6 confirmed), 4 possible ovarian or appendicular pathology (1 appendicitis), 4 to confirm the histological nature of an ovarian tumor (2 functional cysts, 1 old TNA, 1 dermoid cyst), 3 suspected salpingitis (2 confirmed), and 2 chronic pelvic pain (1 endometriosis). No pathology was found in 2 cases, and in 1 case pelvic adhesions prevented confirmation of the diagnosis. Thirteen laparoscopically-guided surgical acts were performed: 2 detorsions of adnexa, 2 excisions of necrosed adnexa and 9 punctures with or without biopsy for functional cysts. Intralaparoscopic detorsion of TNA was complicated in one case by fibrinolysis requiring secondary laparotomy. Mean hospitalisation was 3 days (range 1 to 16). the preferential therapeutic indications for laparoscopy in the child are transposition of an ovary and ablation of the gonads in case of sexual ambiguity. It is used diagnostically in cases of sudden pelvic pain. In addition to this diagnostic role, it now allows most treatments to be carried out (detorsion with or without fixation, transparietal cystectomy), including those for associated lesions (appendicectomy). Its morbidity is quite low, which warrants increasing the number of indications in pediatric pathology.

Adolescent↗
PubMed1993

[Incidence of the form and caliber of urethral resistance. Evaluation for a normal masculine urethra and in cases of obstruction due to prostatic hypertrophy].

Certain forms of benign prostatic hypertrophy are associated with a reduction of the calibre of the prostatic urethra of the median lobe, a defect of infundibulisation of the bladder neck and a dilated appearance of the bulbar urethra. The objective of this study was to verify whether hydrodynamic arguments could be used to confirm the concept that defective infundibulisation of the bladder neck is directly responsible for an obstructive syndrome or via a reduction in the calibre of the bladder neck orifice. More generally, this study was designed to quantify the distribution of resistance to flow along the normal urethra and to define the role of cervicoprostatic and urethral deformities in the obstruction associated with benign prostatic hypertrophy. Urodynamic studies are unable to answer this question, as the instantaneous urethral resistance is evaluated globally by the Pressure-Flow relation. The authors performed morphological analysis to divide the urethra into simple hydraulic segments for which the corresponding pressure drop coefficients were calculated. These coefficients constitute an approach to segmental resistance to flow and can be used to quantify changes in shape observed on voiding urethrography or ultrasonography. Digital analysis of voiding urethrographies showed that, under normal conditions, urethral resistance was regularly distributed along the urethra and essentially depended on friction of the urethral wall. In the case of benign prostatic hypertrophy, even with a median lobe, the increase in the pressure drop coefficients was due to a reduction in the calibre of the bladder neck orifice and prostatic urethra. Cervical deformities appeared to be minimally obstructive, according to urodynamic parameters, if they were not associated with a reduction in the calibre of the bladder neck orifice.

Evaluation Studies as Topic↗
PubMed1992

The three-dimensional structure of the tenth type III module of fibronectin: an insight into RGD-mediated interactions.

The solution structure of the tenth type III module of fibronectin has been determined using nuclear magnetic resonance techniques. The molecule has a fold similar to that of immunoglobulin domains, with seven beta strands forming two antiparallel beta sheets, which pack against each other. Both beta sheets contribute conserved hydrophobic residues to a compact core. The topology is more similar to that of domain 2 of CD4, PapD, and the extracellular domain of the human growth hormone receptor than to that of immunoglobulin C domains. The module contains an Arg-Gly-Asp sequence known to be involved in cell adhesion. This tripeptide is solvent exposed and lies on a conformationally mobile loop between strands F and G, consistent with its cell adhesion function.

Amino Acid Sequence↗
PubMed1992

Solution structure of the fibrin binding finger domain of tissue-type plasminogen activator determined by 1H nuclear magnetic resonance.

The amino acid sequence of the first domain of tissue-type plasminogen activator (t-PA) includes eight residues that are highly conserved in the type 1 finger domains found in human fibronectin. A construct comprising 50 residues from this finger domain of t-PA has been expressed and its solution structure has been determined by two-dimensional nuclear magnetic resonance spectroscopy. A total of 782 experimental restraints consisting of 723 interproton distances derived from nuclear Overhauser effect measurements, 43 torsion angles, and 16 hydrogen bond restraints were used as the input for dynamical simulated annealing structure calculations. Twenty-eight structures were obtained that satisfied the experimental data with no single distance violation greater than 0.3 A. The average atomic root-mean-square distribution for the backbone atoms of the final structures was 0.41 (+/- 0.13) A for the well defined part of the structure (residues 4 to 47). The overall fold of the t-PA finger domain shows a striking similarity to that of the seventh type 1 repeat of human fibronectin with the side-chains of conserved residues lying in similar conformations. One significant difference between the two molecules is that hydrophobic residues cover the exposed surface of the principal beta-sheet region in the t-PA finger domain. It is suggested that one face of this region may interact with parts of the complete t-PA protein.

Amino Acid Sequence↗
PubMed1992

A selectable bifunctional beta-galactosidase::phleomycin-resistance fusion protein as a potential marker for eukaryotic cells.

The Sh ble gene, conferring phleomycin resistance (PhR), was fused in frame to both the 3' and 5' ends of the Escherichia coli lacZ gene. The bifunctionality of the resulting 130-kDa hybrid proteins was demonstrated in E. coli and in the fungus, Tolypocladium geodes. PhR transformants of both organisms could be selected for. All transformants from E. coli and most from T. geodes displayed beta Gal activity. In the fungal host, higher transformation frequencies and greater levels of beta Gal activity were observed in clones harboring the lacZ::Sh ble fusion, as compared to the Sh ble::lacZ configuration. This system appears to be a potentially useful tool for the direct selection of transformants, and the evaluation of gene expression and regulation in a wide variety of prokaryotic and eukaryotic hosts.

Amino Acid Sequence↗
PubMed1992

1H NMR assignment and secondary structure of the cell adhesion type III module of fibronectin.

The secondary structure of the tenth type III module from human fibronectin has been determined using NMR. This type of module appears many times in a wide variety of proteins. The type III module described here contains an Arg-Gly-Asp sequence known to be involved in cell-cell adhesion. The module was expressed in yeast and characterized by amino acid sequencing and mass spectrometry. 2D and 3D NMR spectroscopy of 15N-labeled protein was used to perform sequence-specific assignment of the spectrum. The secondary structure was defined by patterns of nuclear Overhauser effects, 3JNH-alpha CH spin-spin coupling constants, and amide proton solvent exchange rates. The molecule consists of seven beta-strands in two antiparallel beta-sheets with an immunoglobulin-like fold similar to that predicted for homologous modules in the cytokine receptor super family [Bazan, J. F. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 6934-6938]. The Arg-Gly-Asp sequence is located on a loop between the beta-strands F and G.

Amino Acid Sequence↗
PubMed1992

The three-dimensional structure of the first EGF-like module of human factor IX: comparison with EGF and TGF-alpha.

The three-dimensional structure of the first epidermal growth factor (EGF)-like module from human factor IX has been determined in solution using two-dimensional nuclear magnetic resonance (in the absence of calcium and at pH 4.5). The structure was found to resemble closely that of EGF and the homologous transforming growth factor-alpha (TGF-alpha). Residues 60-65 form an antiparallel beta-sheet with residues 68-73. In the C-terminal subdomain a type II beta-turn is found between residues 74 and 77 and a five-residue turn is found between residues 79 and 83. Glu 78 and Leu 84 pair in an antiparallel beta-sheet conformation. In the N-terminal region a loop is found between residues 50 and 55 such that the side chains of both are positioned above the face of the beta-sheet. Residues 56-60 form a turn that leads into the first strand of the beta-sheet. Whereas the global fold closely resembles that of EGF, the N-terminal residues of the module (46-49) do not form a beta-strand but are ill-defined in the structure, probably due to the local flexibility of this region. The structure is discussed with reference to recent site-directed mutagenesis data, which have identified certain conserved residues as ligands for calcium.

Amino Acid Sequence↗
PubMed1992

Efficient secretion of human lysozyme fused to the Sh ble phleomycin resistance protein by the fungus Tolypocladium geodes.

Tolypocladium geodes strain NC50 was transformed by different integrating vectors bearing both a synthetic gene encoding human lysozyme (HLz) and the Sh ble phleomycin resistance marker, either in separate expression cassettes or in transcriptional or translational fusion configurations. Clones derived from all vectors were able to secrete HLz. The highest productivities in shake flasks (up to 150 mg l-1 in 5 days) were obtained when HLz was fused at the C-terminal end of the Sh ble protein. The fusion protein is efficiently secreted and release of active lysozyme occurs by extracellular proteolytic cleavage in the junction peptide.

Amino Acid Sequence↗
PubMed1992

Ligand requirements for Ca2+ binding to EGF-like domains.

Site-specific mutagenesis studies of the first epidermal growth factor-like (EGF-like) domain of human clotting factor IX suggest that the calcium-binding site present in this domain (dissociation constant Kd = 1.8 mM at pH 7.5 and ionic strength I = 0.15) involved the carboxylate residues Asp47, Asp49 and Asp64. To further characterize the ligands required for calcium binding to EGF-like domains, two new mutations, Asp47----Asn and Asp49----Asn, were introduced into the domain by peptide synthesis. 1H-NMR spectroscopy was used to obtain the dissociation constants for calcium binding to these mutations. Calcium binding to the Asp49----Asn modified domain is only mildly affected (Kd = 6 mM, I = 0.15), whereas binding to the Asp47----Asn modified domain is severely reduced (Kd = 42 mM, I = 0.15). From these data, it is proposed that the anionic oxygen atoms of the side chains of residues 47 and 64 are essential for calcium binding, whereas the side chain ligand for calcium at residue 49 can be a carboxyamide oxygen. As a control, the introduction of the modification Glu78----Asp in a region of the domain not believed to be involved in calcium binding had very little effect on the Kd for calcium (Kd = 2.6 mM, I = 0.15). Finally, the effect of an Asp47----Gly substitution found in the natural haemophilia B mutant, factor IXAlabama, was investigated. This peptide has a markedly reduced affinity for calcium (Kd = 37 mM, I = 0.15), suggesting that the defect in factor IXAlabama is due to impaired calcium binding to its first EGF-like domain.

Amino Acid Sequence↗