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Biomedical subjects

G Joseph

Publications and source records attributed to G Joseph.

At least 19 recordsLinked to original sources
PubMed1999

Genetic variation and intergenerational FMR1 CGG-repeat stability in 100 unrelated three-generation families from the normal population.

In order to identify genetic factors governing expansion of the CGG repeat in the FMR1 gene and to determine what predisposes or causes a normal stable allele to change to an unstable premutation allele, it is essential to study and understand the basis of normal variation. The aim of this study was to investigate genetic variation and intergenerational stability of the FMR1 CGG-repeat region in 100 unrelated three-generation families from the general population (651 meioses). The number of CGG-repeats in the FMR1 gene was determined in all 750 individuals from the 100 families (a total of 1,132 X-chromosomes), and the allele frequencies and variability were analyzed. Thirty-six different alleles (12-60 repeats) were seen with 30 (45.8%) as the most common allele; overall female heterozygosity was 73%. Most (>96%) of the normal array lengths were less than 40 repeats. Fifteen families with at least one allele equal to or greater than 40 repeats (40-60) were identified; in one of these families there was an increase of one triplet repeat during transmission from a mother to son. These findings, together with future molecular analyses, may provide data to test proposed models that attempt to explain the mutational process and the population dynamics of the triplet repeat region of the FMR1 gene, including the transition from normal to unstable alleles, or to test other putative cis-acting sequences that may be involved with instability in the FMR1 gene.

Alleles↗
PubMed1999

Distribution of variable vs fixed costs of hospital care.

CONTEXT: Most strategies proposed to control the rising cost of health care are aimed at reducing medical resource consumption rates. These approaches may be limited in effectiveness because of the relatively low variable cost of medical care. Variable costs (for medication and supplies) are saved if a facility does not provide a service while fixed costs (for salaried labor, buildings, and equipment) are not saved over the short term when a health care facility reduces service. OBJECTIVE: To determine the relative variable and fixed costs of inpatient and outpatient care for a large urban public teaching hospital. DESIGN: Cost analysis. SETTING: A large urban public teaching hospital. MAIN OUTCOME MEASURES: All expenditures for the institution during 1993 and for each service were categorized as either variable or fixed. Fixed costs included capital expenditures, employee salaries and benefits, building maintenance, and utilities. Variable costs included health care worker supplies, patient care supplies, diagnostic and therapeutic supplies, and medications. RESULTS: In 1993, the hospital had nearly 114000 emergency department visits, 40000 hospital admissions, 240000 inpatient days, and more than 500000 outpatient clinic visits. The total budget for 1993 was $429.2 million, of which $360.3 million (84%) was fixed and $68.8 million (16%) was variable. Overall, 31.5% of total costs were for support expenses such as utilities, employee benefits, and housekeeping salaries, and 52.4% included direct costs of salary for service center personnel who provide services to individual patients. CONCLUSIONS: The majority of cost in providing hospital service is related to buildings, equipment, salaried labor, and overhead, which are fixed over the short term. The high fixed costs emphasize the importance of adjusting fixed costs to patient consumption to maintain efficiency.

Chicago↗
PubMed1999

Catheter-based techniques for closure of coronary fistulae.

This study details different methodologies of percutaneous closure of arteriosystemic and arteriovenous coronary fistula. Seven patients underwent transcatheter intervention of 10 fistulas, with 7 fistulas successfully closed: 6 with embolic coil devices and 1 with a covered stent obstructing the fistula ostium. The major complication encountered was one death as a result of device recoil into a major epicardial vessel. Percutaneous transcatheter closure of coronary fistulas appears to be simple, facile, and effective. However, device recoil into an undesired arterial segment, while irritating in a noncoronary arterial tree, may be catastrophic when occurring in an epicardial coronary artery.

Aged↗
PubMed1999

Right internal jugular vein approach as an alternative in balloon pulmonary valvuloplasty.

Transjugular balloon pulmonary valvuloplasty was safely and successfully performed in five patients, two of whom had severe right heart failure. Crossing the stenotic pulmonary valve from the right internal jugular vein was consistently easy and quick. This approach should be considered whenever difficulties are experienced or anticipated in the femoral approach.

Adolescent↗
PubMed1999

Definitive percutaneous treatment of Lutembacher's syndrome.

Definitive percutaneous treatment of a patient with Lutembacher's syndrome was successfully accomplished using the Amplatzer septal occluder to close a secundum atrial septal defect and the Joseph mitral balloon catheter to dilate rheumatic mitral valve stenosis. Transcatheter therapy is an effective alternative to surgery in selected patients with Lutembacher's syndrome. Cathet. Cardiovasc. Intervent. 48:199-204, 1999.

Adult↗
PubMed1999

Morphologic proof of the toxicity of mitomycin C on the ciliary body in relation to different application methods.

BACKGROUND: Since postoperative hypotony has been a frequent complication of glaucomatous filtration surgery with adjunctive use of mitomycin C (MMC), the question arises of whether there may be another application method which can minimize this side effect. The purpose of this study was to establish the morphologic side effects of different application methods. METHODS: MMC 0.2 mg/ml was applied to the episclera of nine eyes of six pigmental rabbits at random via collagen shield (CS), soft contact lens (CL), or lyophilisate (20 microg; LY) for 5 min. Two eyes (controls) had a subconjunctival injection of BSS only. Another control eye was left untreated (no injection). No trabeculectomy was performed. One hour later the amounts of MMC in the conjunctiva and aqueous were analyzed by reverse-phase high-pressure liquid chromatography. Ciliary bodies were dissected from the enucleated eyes, embedded and investigated by transmission electron microscopy (TEM). Cell height of the nonpigmented ciliary epithelium was morphometrically assessed by means of computer-assisted image analysis. RESULTS: The light-microscopic analysis of the sectioned cell area revealed reduction of the cell height of the non-pigmented ciliary epithelium (NPCE) after application with soft contact lens (fourfold) and collagen shield (2.5-fold) but not with lyophilisate compared to the untreated eye. The following ultrastructural changes were seen: loss of apical microvilli (CS, CL, LY), disintegrating melanin granules within NPCE (CS), lysis of entire areas with NPCE cells (CS), myelin figures within mitochondria (LY), intracellular vacuoles (CS, CL), lysis of myelinated nerves (CS), myelin figures in mitochondria of endothelial cells (LY), and lysis of stromal fibrocytes (CS). In the control eyes (injection of BSS) none of these ultrastructural changes were detected in the cylindrical NPCE cells. The concentration of mitomycin in the aqueous humor after topical application of MMC on the episclera for 5 min were all below the detection limit (<10 ng/ml). The concentration of MMC in the conjunctiva ranged from 2.1 to 3.7 microg/g. CONCLUSION: Severe morphologic alterations were seen at the electron-microscopic level after application of MMC 0.2 mg/ml with a collagen shield and with a soft contact lens. They were mildest with lyophilisate and absent in the BSS controls. A new administration device is needed if trabeculectomy is to be performed successfully using MMC in human glaucomatous eyes.

Animals↗
PubMed1999

Surgical management of angiographically occult spinal dural arteriovenous fistulae (type I spinal arteriovenous malformations): three technical case reports.

OBJECTIVE AND IMPORTANCE: Spinal dural arteriovenous fistulae (Type I spinal arteriovenous malformations [AVMs]) have been recognized as a treatable cause of progressive myelopathy. The diagnosis and characterization of these lesions rest heavily on spinal angiography. CLINICAL PRESENTATION: We present three patients whose clinical presentations were consistent with a spinal dural AVM but whose spinal angiographic results were negative. INTERVENTION: The surgical treatment of these angiographically occult spinal AVMs is described. In retrospect, in each case, the feeding vessel to the AVM was injected but not seen. CONCLUSION: Some spinal dural arteriovenous fistulae will be angiographically occult. If the clinical and radiographic presentations strongly suggest the presence of an arteriovenous fistula, surgical exploration should be considered.

Aged↗
PubMed1998

Mapping of functional domains in p47(phox) involved in the activation of NADPH oxidase by "peptide walking".

The superoxide generating NADPH oxidase of phagocytes consists, in resting cells, of a membrane-associated electron transporting flavocytochrome (cytochrome b559) and four cytosolic proteins as follows: p47(phox), p67(phox), p40(phox), and the small GTPase, Rac(1 or 2). Activation of the oxidase is consequent to the assembly of a membrane-localized multimolecular complex consisting of cytochrome b559 and the cytosolic components. We used "peptide walking" (Joseph, G., and Pick, E. (1995) J. Biol. Chem. 270, 29079-29082) for mapping domains in the amino acid sequence of p47(phox) participating in the molecular events leading to the activation of NADPH oxidase. Ninety-five overlapping pentadecapeptides, with a four-residue offset between neighboring peptides, spanning the complete p47(phox) sequence, were tested for the ability to inhibit NADPH oxidase activation in a cell-free system. This consisted of solubilized macrophage membranes, recombinant p47(phox), p67(phox), and Rac1, and lithium dodecyl sulfate, as the activator. Eight functional domains were identified and labeled a-h. These were (N- and C-terminal residue numbers are given for each domain) as follows: a (21-35); b (105-119); c (149-159); d (193-207); e (253-267); f (305-319); g (325-339), and h (373-387). Four of these domains (c, d, e, and g) correspond to or form parts of regions shown before to participate in NADPH oxidase assembly. Thus, domain c corresponds to a region on the N-terminal boundary of the first src homology 3 (SH3) domain, whereas domains d and e represent more precisely defined sites within the full-length first and second SH3 domains, respectively. Domain g overlaps an extensively investigated arginine-rich region. Domains a and b, in the N-terminal half of p47(phox), and domains f and h, in the C-terminal half, represent newly identified entities, for which there is no earlier experimental evidence of involvement in NADPH oxidase activation. "Peptide walking" was also applied to the identification of domains in p47(phox) mediating binding to p67(phox). This was done by quantifying, by enzyme-linked immunosorbent assay, the binding of p67(phox), in solution, to a series of 95 overlapping biotinylated p47(phox) peptides, attached to streptavidin-coated 96-well plates. A single proline-rich domain (residues 357-371) was found to bind p67(phox) in the absence and presence of lithium dodecyl sulfate.

Amino Acid Sequence↗
PubMed1998

Glucosylation and ADP ribosylation of rho proteins: effects on nucleotide binding, GTPase activity, and effector coupling.

We studied the effects of glucosylation of RhoA, Rac1, and Cdc42 at threonine-35 and -37 by Clostridium difficile toxin B on nucleotide binding, GTPase activity, and effector coupling and compared these results with the ADP ribosylation of RhoA at asparagine-41 catalyzed by Clostridium botulinum C3 transferase. Whereas glucosylation and ADP ribosylation had no major effects on GDP release from RhoA, Rac1, and Cdc42, the rate of GTPgammaS release from Rho proteins was increased 3-6-fold by glucosylation. ADP ribosylation decreased the rate of GTPgammaS release by about 50%. Glucosylation reduced the intrinsic activities of the GTPases by 3-7-fold and completely blocked GTPase stimulation by Rho-GAP. In contrast, ADP ribosylation slightly increased GTPase activity ( approximately 2-fold) and had no major effect on GAP stimulation of GTPase. Whereas ADP ribosylation did not affect the interaction of RhoA with the binding domain of protein kinase N, glucosylation inhibited this interaction. Glucosylation of Rac1 markedly diminished its ability to support the activation of the superoxide-generating NADPH oxidase of phagocytes. Glucosylated Rac1 did not interfere with NADPH oxidase activation by unmodified Rac1, even when present in marked molar excess, indicating that it was incapable of competing for a common effector. The data indicate that the functional inactivation of small GTPases by glucosylation is mainly caused by inhibition of GTPase-effector protein interaction.

ADP Ribose Transferases↗
PubMed1997

Sensitive and convenient high-performance liquid chromatographic method for the determination of mitomycin C in human plasma.

An improved high-performance liquid chromatographic assay for the cytostatic drug mitomycin C in plasma is presented. The principal steps are precipitation of plasma proteins with acetonitrile, lyophilization of the supernatant and reversed-phase chromatography on a Hypersil ODS 5 microm column with 0.01 M NaH2PO4 buffer (pH 6.5)-methanol (70:30, v/v) in isocratic mode. At a flow-rate of 1.3 ml/min a column pressure of 180-220 bar resulted. Porfiromycin served as internal standard. UV detection was performed at 365 nm. Quantitation limit based on a coefficient of variation <10% in intra- and inter-day assay was 5 microg/l mitomycin C, detection limit based on a signal-to-noise ratio of 3 was 1 microg/l. Recovery was 100% and linearity was shown for the whole range of concentration (1-500 microg/l). None of the five drugs used during chemoembolisation interfered with the assay in vitro. The assay meets the requirements for pharmacokinetic studies of mitomycin C in patients as regards sensitivity and ease of use.

Antineoplastic Agents, Alkylating↗
PubMed1997

Two RNA-binding domains determine the RNA-binding specificity of nucleolin.

Nucleolin is an abundant nucleolar RNA-binding protein that seems to be involved in many aspects of ribosome biogenesis. Nucleolin contains four copies of a consensus RNA-binding domain (CS-RBD) found in several other proteins. In vitro RNA-binding studies previously determined that nucleolin interacts specifically with a short RNA stem-loop structure. Taken individually, none of the four CS-RBDs interacts significantly with the RNA target, but a peptide that contains the first two adjacent CS-RBDs (R12) is sufficient to account for nucleolin RNA-binding specificity and affinity. The full integrity of these two domains is required, since N- or C-terminal deletion abolishes the specific interaction with the RNA. Mutation of conserved amino acids within the RNP-1 sequence of CS-RBD 1 or 2 drastically reduces the interaction with the RNA, whereas mutation of the analogous residues in CS-RBDs 3 and 4 has no effect in the context of the R1234G protein (which corresponds to the C-terminal end of nucleolin). Our results demonstrate that nucleolin RNA-binding specificity is the result of a cooperation between two CS-RBDs (RBDs 1 and 2) and also suggests a direct or indirect involvement of the RNP-1 consensus sequence of both CS-RBDs in the recognition of the RNA target.

Animals↗
PubMed1997

Transseptal approach to aortography and carotid artery stenting in pulseless disease.

We report on a patient with pulseless disease (Takayasu's arteritis) in whom access to the central circulation by extremity arterial cannulation was not possible due to absent pulses in all four limbs. The transseptal approach was used for aortography, bilateral selective carotid angiography, and successful elective stent deployment in the right common carotid artery.

Adult↗
PubMed1997

Mechanisms of cardiac perforation leading to tamponade in balloon mitral valvuloplasty.

Mechanisms of cardiac perforation in 10 cases of cardiac tamponade encountered in a single-center series of 903 balloon mitral valvuloplasty procedures were elucidated by precise localization of the site of perforation at subsequent surgery. These mechanisms were perforation of the aortic root and adjacent right atrium by sliding up of the transseptal set (2), apical tears by straight-tip balloon catheters driven distally during mitral valve dilatation (3), apical perforations by guidewires introduced through catheters wedged in the apex (2), tear of the posterior right atrial wall by dilatation of the track produced by very low septal punctures (2), and right ventricular perforation by a pacing catheter (1). Multivariate analysis showed cardiac perforation to be significantly related to the total experience at the center (inversely) and to patient age (directly). Left ventricular perforation occurred exclusively in patients > 40 yr of age. Understanding these mechanisms has enabled formulation of effective strategies to prevent cardiac perforation.

Adolescent↗
PubMed1997

Combined brachial and femoral approach to balloon angioplasty in coarctation of aorta.

Transfemoral balloon angioplasty of native aortic coarctation was initially not feasible in two patients, because of inability to cannulate the femoral artery percutaneously in one, and to cross the coarctation in the other. The percutaneous brachial approach helped overcome both these problems, after which utilization of intravascular snares allowed successful transfemoral completion of angioplasty.

Adult↗