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Biomedical subjects

G Feldman

Publications and source records attributed to G Feldman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Development of a decision aid for atrial fibrillation who are considering antithrombotic therapy.

With patients demanding a greater role in the clinical decision-making process, many researchers are developing and disseminating decision aids for various medical conditions. In this article, we outline the essential elements in the development and evaluation of a decision aid to help patients with atrial fibrillation choose, in consultation with their physicians, appropriate antithrombotic therapy (warfarin, aspirin, or no therapy) to prevent stroke. We also outline possible future directions regarding the implementation and evaluation of this decision aid. This information should enable clinicians to better understand the role that decision aids may have in their interactions with patients.

Anticoagulants↗
PubMed2000

Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31.

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling, autosomal-dominant disorder of connective tissue and is characterized by postnatal progressive heterotopic ossification of muscle, tendon, ligament, and fascia and by congenital malformation of the great toes. To identify the chromosomal location of the FOP gene, we conducted a genomewide linkage analysis, using four affected families with a total of 14 informative meioses. Male-to-male transmission of the FOP phenotype excluded X-linked inheritance. Highly polymorphic microsatellite markers covering all human autosomes were amplified by use of PCR. The FOP phenotype is linked to markers located in the 4q27-31 region (LOD score 3.10 at recombination fraction 0). Crossover events localize the putative FOP gene within a 36-cM interval bordered proximally by D4S1625 and distally by D4S2417. This interval contains at least one gene involved in the bone morphogenetic protein-signaling pathway.

Chromosome Mapping↗
PubMed2000

Gamma ray nuclear resonance absorption: an alternative method for in vivo body composition studies.

We have evaluated gamma ray nuclear resonance absorption (gamma-NRA) on nitrogen, a mature technology proposed and developed by Soreq NRC for detecting explosives, as an alternative to neutron activation for in vivo assaying of body nitrogen. The principles of the gamma-NRA method are outlined, and a test facility constructed at McMaster University's Accelerator Laboratory is described. The results of a feasibility study recently performed there on phantoms and animal tissue are presented and discussed. gamma-NRA is a full imaging technique that essentially constitutes element-specific absorptiometry--i.e., it can generate projections of the mass distribution for a specific element, along with a conventional radiograph of the patient. From the transmission profile of an individual scanned by 9.17 MeV gamma rays, local or whole body nitrogen content can be determined via the resonant attenuation undergone when the beam encounters regions of nitrogen concentration. The advantages of gamma-NRA over neutron activation are (a) radiation doses delivered to the body are at least one order of magnitude lower, thus allowing repeated measurements on individual patients and also rendering the method ethically acceptable for application to children; (b) gamma-NRA is inherently free from uncertainties related to nonuniform distributions of the element in question within the body; (c) it is applicable to patients of varying size and shape; and (d) it yields both nitrogen images and conventional radiographic images of the body.

Animals↗
PubMed1999

Spontaneous down-regulation of Fas-associated phosphatase-1 may contribute to excessive apoptosis in myelodysplastic marrows.

In this study, we examined the role of Fas-signaling in the apoptotic pathway in myelodysplastic syndromes (MDS). Ficoll-separated mononuclear cells from 18 bone marrow aspirate specimens obtained from 17 MDS patients, 4 normal healthy donors, and 3 acute myeloid leukemia patients transformed from MDS (t-AML) were studied for mRNA expression of Fas-L, Fas, and the effectors of their signaling, Caspase 1 and Caspase 3, using reverse transcriptase polymerase chain reaction. Fas-L, Fas, and Caspase 1 were detectable in all of the samples in the three groups. Caspase 3 was detectable both in MDS and t-AML specimens but was negligible in normal cells. The apoptotic index (AI%) determined by in situ end labeling of fragmented DNA in 4-hour cultures of mononuclear cells was significantly higher in MDS cells compared to normal or t-AML cells (mean +/- SEM: 2.3% +/- 0.4% in MDS, n = 10 vs. 0.6% +/- 0.2%, n = 4, P = 0.014 in normal cells, and 0.2% +/- 0.2%, n = 3, P = 0.007 in t-AML cells). Treatment of MDS cells with anti-Fas-L antibody suppressed apoptosis (AI%: 2.1% +/- 0.6% in untreated vs. 1.37% +/- 0.5% in treated, n = 6, P = 0.02), indicating functional participation of Fas-signaling in MDS. Further, it was found that Fas-L, Fas, and Caspase 1 mRNA expression remained unchanged in 4 hours. Caspase 3 expression appeared in normal cells after 4 hours and was present at both 0 and 4 hours in MDS and t-AML cells. In contrast to persistent expression in normal and t-AML cells, cells from the 5 MDS patients studied consistently showed significantly lowered or undetectable expression of a negative regulator of Fas, called Fas-associated phosphatase-1 (Fap-1) after 4 hours. Thus, the high AI% in MDS corresponds to a rapid decline in Fap-1. Furthermore, in tumor necrosis factor alpha (TNF-alpha) treated HL60 promyelocytic cells, a definite periodicity in the expression of different mRNAs was observed with upregulation of TNF-alpha itself at 30 minutes, increased expression of Fas and the appearance of Fas-L after 2 hours, and a decrease in Fap-1 expression after 8 hours. These results suggest that TNF-alpha not only induces the effectors of Fas-signaling but also may downregulate the inhibitor. We conclude that a spontaneous and rapid down-regulation of Fap-1, possibly induced by TNF-alpha, a cytokine shown to be present in excess in MDS marrows, may underlie the increased apoptotic death of hematopoietic cells in these patients. Interference with Fap-1 turnover may provide a new therapeutic modality for MDS.

Apoptosis↗
PubMed1998

Opitz G/BBB syndrome in Xp22: mutations in the MID1 gene cluster in the carboxy-terminal domain.

The MID1 gene in Xp22 codes for a novel member of proteins containing a RING finger, B-box, coiled-coil and a conserved C-terminal domain. Initially, three mutations in the C-terminal region were found in patients with Opitz G/BBB syndrome, a defect of midline development. Here we have determined the complete gene structure of the MID1 gene and have analyzed all nine exons for mutations in a set of 40 unrelated Opitz G/BBB patients. We now report six additional mutations all clustered in the carboxy-terminal domain of the MID1 protein. These data suggest that this conserved domain of the B-box proteins may play a fundamental role in the pathogenesis of Opitz syndrome and in morphogenetic events at the midline during blastogenesis.

Abnormalities, Multiple↗
PubMed1998

Pointing to remembered targets in 3-D space in Parkinson's disease.

A three-dimensional tracking system was used to examine whether subjects with Parkinson's disease (PD) would show characteristic performance deficits in an unconstrained pointing task. Five targets were presented in a pyramidal array in space to 11 individuals with mild to moderate PD and 8 age-matched controls. After the target was indicated, subjects closed their eyes and pointed to the remembered target locations without vision. Despite the absence of visual feedback during movement, PD subjects were as accurate overall as controls. However, PD subjects showed greater variable errors, more irregular trajectories, and a vertical endpoint bias in which their endpoints were significantly lower than controls. They also showed deficiencies in the compensatory organization of joint rotations to ensure consistency in azimuthal (horizontal) positioning of the arm endpoint. We concluded that, under appropriate task conditions, PD subjects may not show overall deficits in accuracy even when making targeting movements at normal speed without visual feedback. Nevertheless, our findings indicate that there are certain dimensions of performance which are selectively altered in Parkinson's disease even when overall performance is normal.

Aged↗
PubMed1998

Bilateral spontaneous avascular necrosis of the navicular. Case presentation with comparative imaging.

It is unusual to find such extensive deformity of the navicular in a bilateral and symmetrical fashion. The apparent lack of significant trauma coupled with the patient's unremarkable medical history led the authors to an exclusionary diagnosis of spontaneous osteonecrosis. While changes are clearly evident on plain film radiography, computed tomography and magnetic resonance imaging provide the clinician with a more detailed picture of the extent of destruction.

Humans↗
PubMed1997

Mapping of a cytoplasmic domain of the human growth hormone receptor that regulates rates of inactivation of Jak2 and Stat proteins.

It has been previously demonstrated that growth hormone (GH)-stimulated tyrosine phosphorylation of Jak2 and Stat5a and Stat5b occurs in FDP-C1 cells expressing either the entire GH receptor or truncations of the cytoplasmic domain expressing only the membrane-proximal 80 amino acids. However, other receptor domains that might modulate rates of GH activation and inactivation of this cascade have not been examined. Here we have defined a region in the human GH receptor between amino acids 520 and 540 in the cytoplasmic domain that is required for attenuation of GH-activated Jak/Stat signaling. Immunoprecipitations with antibodies to Jak2 indicate that the protein tyrosine phosphatase SHP-1 is associated with this kinase in cells exposed to GH. To address the possibility that SHP-1 could function as a negative regulator of GH signaling, liver extracts from motheaten mice deficient in SHP-1 or unaffected littermates were analyzed for activation of Stats and Jak2. Extracts from motheaten mice displayed prolonged activation of the Stat proteins as measured by their ability to interact with DNA and prolonged tyrosine phosphorylation of Jak2. These results delineate a novel domain in the GH receptor that regulates the inactivation of the Jak/Stat pathway and appears to be modulated by SHP-1.

Animals↗
PubMed1997

Infantile-onset multisystem inflammatory disease: a differential diagnosis of systemic juvenile rheumatoid arthritis.

We describe four unrelated children with neonatal maculopapular rash, fever, arthritis, hepatosplenomegaly, lymphadenopathy, eye involvement, and neurologic symptoms. Radiographs of the joints were surprisingly similar, showing an abnormal epiphyseal and metaphyseal appearance. These clinical and radiologic findings allowed us to include these children in a very peculiar syndrome described as infantile-onset multisystemic inflammatory disease. A chondrosarcoma developed in one of our patients.

Adolescent↗
PubMed1996

The metabolic organization of the adult human liver: a comparative study of normal, fibrotic, and cirrhotic liver tissue.

Little is known about the alterations of metabolic organization of the human liver tissue in chronic liver diseases. We therefore compared the distribution of the following zonal metabolic markers in 10 samples of normal liver tissue, 10 samples of fibrotic tissue, and 22 samples of cirrhotic tissue: (a) the enzymatic activities of glucose-6-phosphatase (G6P), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), nicotinamide-adenine-dinucleotide-phosphate [NAPH] dehydrogenase (ND), beta-hydroxybutyrate dehydrogenase (HBDH), and glutamate dehydrogenase (GDH); (b) the protein glutamine synthetase (GLS); and (c) albumin messenger RNA (mRNA). The normal human hepatic lobule was characterized by the periportal predominance of G6P and SDH enzymatic activities and albumin mRNAs, the perivenous predominance of ND and GDH, the restriction of GLS to a small perivenous compartment, and the predominanc of beta-HBDH at the contact of both portal tracts and centrilobular veins. In fibrosis, the overall metabolic organization of the normal liver tissue was retained. The expression of periportal markers predominated around enlarged portal tracts and that of perivenous markers around residual centrilobular veins. GLS was constantly detected at the contact of centrilobular veins. In cirrhotic nodules, no zonation was observed for most enzymatic activities or for albumin. Only G6P usually predominated at the periphery of the nodules. GLS was constantly undetectable. No difference accordingly to the etiology of the underlying disease was observed. In conclusion, the normal human hepatic lobule presents a marked metabolic zonation, preserved in fibrotic lesions, but lost in cirrhotic nodules. The alterations of the metabolic organization observed in cirrhosis might contribute to the pathogenesis of some of the metabolic disorders associated with advanced liver disease.

Adult↗
PubMed1996

Utility of the Pediatric Symptom Checklist as a psychosocial screen to meet the federal Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) standards: a pilot study.

OBJECTIVE: To examine the usefulness of the Pediatric Symptom Checklist (PSC) as the psychosocial screening measure to meet federal Medicaid/Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) standards in a low-income Hispanic community. DESIGN AND SETTING: Three hundred seventy-nine children (aged 6 to 16 years) were screened with the PSC in a 10-month period during well child visits to three clinics in Ventura and San Mateo counties in California. The PSC was available in English and Spanish and was administered both in written (paper-and-pencil) and oral formats. Follow-up services were provided for children identified as needing evaluation. RESULTS: The Cronbach alpha was high (r = 0.91) for the PSC in the whole sample and virtually identical for English, Spanish, oral, and written formats. All the PSC items were significantly associated with total score on the PSC in English, Spanish, oral, and written formats. Overall, the PSC identified 10.6% of the sample as at risk for psychosocial problems. Thirty-six children (9.5% of sample) were referred for mental health follow-up. Public health data from Ventura County showed a statistically significant increase in referrals for psychologic problems during the study period in two locations using the PSC: from 0.5% to 2.9% of the school-aged children seen. CONCLUSION: The PSC provides a feasible, well-accepted method for screening for psychosocial problems during EPSDT examinations of school-aged children. Psychosocial screening using a validated instrument such as the PSC, as well as increased efforts to refer positive screening results, track outcomes, and assess cost benefits should be essential requirements in capitated Medicaid approaches to caring for poor children.

Adolescent↗