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Biomedical subjects

I Feldman

Publications and source records attributed to I Feldman.

At least 19 recordsLinked to original sources
PubMed2003

Bioinformatic analysis of autism positional candidate genes using biological databases and computational gene network prediction.

Common genetic disorders are believed to arise from the combined effects of multiple inherited genetic variants acting in concert with environmental factors, such that any given DNA sequence variant may have only a marginal effect on disease outcome. As a consequence, the correlation between disease status and any given DNA marker allele in a genomewide linkage study tends to be relatively weak and the implicated regions typically encompass hundreds of positional candidate genes. Therefore, new strategies are needed to parse relatively large sets of 'positional' candidate genes in search of actual disease-related gene variants. Here we use biological databases to identify 383 positional candidate genes predicted by genomewide genetic linkage analysis of a large set of families, each with two or more members diagnosed with autism, or autism spectrum disorder (ASD). Next, we seek to identify a subset of biologically meaningful, high priority candidates. The strategy is to select autism candidate genes based on prior genetic evidence from the allelic association literature to query the known transcripts within the 1-LOD (logarithm of the odds) support interval for each region. We use recently developed bioinformatic programs that automatically search the biological literature to predict pathways of interacting genes (PATHWAYASSIST and GENEWAYS). To identify gene regulatory networks, we search for coexpression between candidate genes and positional candidates. The studies are intended both to inform studies of autism, and to illustrate and explore the increasing potential of bioinformatic approaches as a compliment to linkage analysis.

Autistic Disorder↗
PubMed1999

Developing a managed care delivery system in New York State for Medicaid recipients with HIV.

In the state of New York, models of care known as HIV Special Needs Plans (HIV SNPs) are being developed to meet the unique health and medical needs of Medicaid recipients with HIV. Establishing managed care plans for the 80,000 to 100,000 HIV-infected Medicaid recipients residing in the state has required considerable effort, including distributing planning grants to solicit information and recommendations regarding program and fiscal policy; convening a workgroup to facilitate discussions between the state and the provider and consumer communities; conducting a longitudinal survey to assess the impact of managed care on persons with HIV; and developing a longitudinal, person-based, encounter-level database representing the clinical and service utilization histories of more than 100,000 patients for state fiscal years 1990 to 1996. The key fiscal issues identified and discussed were capitation rates, initial capitalization levels, and risk-adjustment mechanisms. Other pertinent issues included the importance of a benefits package supporting a comprehensive, integrated continuum of state-of-the-art services; marketing and enrollment; attention to provider and consumer training and education needs; and interdependence of financial reimbursement and benefits packages. From our experience in New York State, we conclude that a successful model of Medicaid managed care for persons with HIV should build on the existing infrastructure of services, using a collaborative process among government agencies, healthcare providers, and HIV/AIDS consumer communities. A future challenge lies in the implementation of the HIV SNP model and evaluation of its soundness and ability to ensure quality healthcare services.

Capitation Fee↗
PubMed1998

[Nursing home-acquired pneumonia--guidelines for hospitalization].

To determine if there are any specific features of nursing-home acquired pneumonia we carried out a retrospective study in a nursing home between 1995-1996, based on clinical and laboratory data. We found no correlation between these findings and the severity of pneumonia, so it would be hazardous to determine rigid guidelines. These patients should be treated in the nursing home as long as conditions allow, in order to avoid hospitalization.

Aged↗
PubMed1998

Congenital hypothyroidism screening in the West Bank: a test case for screening in developing regions.

Screening for congenital hypothyroidism (CH) among the Arab population of the West Bank began in May 1987 as part of the neonatal screening program in Israel. In the West Bank many infants are born at home or are released from the hospital on the 1st day after birth and thus cannot be screened. However, we tried to reach the infants before the age of 1 month at the maternal and child health centers, where they receive immunization. In this screening program, 64% of the infants were sampled by the 1st week and 93% by 3 weeks of life. In contrast to the screening in Israel, where thyroxine determination is followed by thyroid-stimulating hormone measurement, in the West Bank thyroid-stimulating hormone was tested first in order to decrease the recall rates. From June 1990 to February 1994, 49,694 infants were screened in the West Bank, of whom 24 with CH were detected (an incidence of 1:2,070). From January 1987 to February 1994, 28,938 infants were screened in East Jerusalem, of whom 20 with CH were detected (incidence 1:1,447). There were differences between the incidence rates in the various districts. The incidence rates were higher than those reported from industrialized countries, but similar to those found in Saudi Arabia. This may be due to the high degree of consanguineous marriages among Arab populations and to environmental factors. In conclusion, in spite of the many difficulties, both practical and political, CH screening in the West Bank is feasible. Although screening all newborns shortly after birth is not possible, this study shows that a high percentage of them can be screened at a time when they can still be effectively treated. Our results could be used in due time as a baseline for a future independent screening program.

Age Distribution↗
PubMed1996

Malignant melanoma of the head and neck. Clinical and immunological considerations.

Prolonged exposure to sun for long periods during most of the year has led to an increase in the frequency of malignant melanoma in Israel, especially for head and neck (H&N) melanoma. H & N melanoma is found in males more than in females and diagnosed when already locally advanced. The disease-free interval between treatment of the primary lesion and recurrence of the disease correlated with the patient's age and the depth of invasion according to Breslow. A higher recurrence rate correlated with male gender, location in the scalp, and the stage of the disease. Metastatic disease involved the lungs, liver, and brain and responded poorly to systemic therapy. Improved survival was related to female gender, early stage of the disease, low Breslow thickness, and location of the primary lesion elsewhere than the scalp. Immunologically, we found that the titers of antimelanoma antibodies in patients with metastatic disease originating in the area of the head and neck were higher than the titer in disease-free H & N melanoma patients (p = 0.05). Moreover, patients with metastatic H & N melanoma had a higher titer of antityrosinase antibodies compared with healthy subjects. These two types of antibodies might be used as markers for disease progression in H & N melanoma. The more aggressive character of H & N melanoma was not reflected by different titers of antimelanoma antibodies nor by antityrosinase antibodies in patients with H & N versus non-H & N melanoma.

Adult↗
PubMed1982

Effects of divalent metal ions on the fluorescence and glucose-quenching of yeast hexokinase isozymes.

Titrations of the quenching of the tryptophan fluorescence of yeast hexokinase isozymes P-I and P-II by Mg2+, Mn2+, Ca2+, Cd2+, and Zn2+ ions and by glucose in the presence of each of these ions (10mM) were performed at pH 5.5 and 6.5 at 20 degrees C. At the higher pH there was a reversal of the type of glucose-binding cooperativity for P-II from negative to positive when either Mn2+ or Ca2+ was present in the buffered isozyme solution before the glucose titration, whereas Mg2+ caused the glucose binding to become noncooperative. Zn2+ and Cd2+ decreased the glucose quenching of P-II fluorescence drastically at pH 5.5, from a value of 15% in buffer to only 4%. Thus, only these two ions, of the five studied, cause the conformation change that results in quenching of the glucose-quenchable cleft tryptophan of P-II. Glucose binding to the P-I isozyme exhibited positive cooperativity in the presence of either Ca2+, Mg2+, or Mn2+, as well as in buffer alone, at both pH's. At the lower pH, Ca2+ enhanced the efficiency of glucose quenching of P-I fluorescence several-fold, while Mn2+ increased it only about 40% and Mg2+ not at all. Further, Ca2+ raised the degree of cooperativity (Hill coefficient) of glucose binding to P-I at this pH from the value of 1.42 in buffer and in the presence of Mg2+ and Mn2+ to 1.94, i.e., almost up to the highest possible value, 2, for dimeric hexokinase. However, at pH 6.5 the Ca2+ effect on the cooperativity was negligible, while Mg2+ and Mn2+ decreased the coefficient from 1.6 in buffer to about 1.4. The biological implications of these diverse metal ion effects are discussed.

Cations, Divalent↗
PubMed1980

Effects of glucose and magnesium ion on the quenching of yeast hexokinase fluorescence by acrylamide.

To probe the effects of the substrate, glucose, and the cofactor, Mg2+, on the structure of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1), titrations of the tryptophan fluorescence of yeast hexokinase isozyme P-II(B) were performed. Acrylamide was used as a quenching titrant in the absence and in the presence of glucose and Mg2+ singly and together at pH 5.5 and 8.3 at 20 degrees C. The four tryptophan residues of the monomeric subunit of yeast hexokinase may be classified as two surface residues, one being highly accessible to dissolved I- and one with restricted accessibility to I-, one glucose-quenchable residue in the cleft, and one buried (Kramp, D.C. and Feldman, I. (1978) Biochim. Biophys. Acta 537, 406--416). The acrylamide data were analyzed by least-squares computer analysis for quenching constants and fractional fluorescence values of the tryptophan residues. The quenching constants measure the accessibilities of the residues to the quencher, while the fractional fluorescences are related to the microenvironments of the fluorophores. At each pH value, glucose altered the quenching constants, but not the fractional fluorescence, of the tryptophan residues. Mg2+ greatly accentuated at this glucose effect, especially for the surface residue near the cleft opening. Comparison of acrylamide- and I-quenching data shows that this particular residue has a positively charged microenvironment. A pH change from 5.5 to 8.3 increased the acylamide-accessibility of the cleft tryptophan but did not seem to influence accessibility of the surface residues or the buried residue significantly, thus strengthening our previous conclusion that the cleft opening is small enough at pH 5.5 to partially restrict entrance of organic molecules and negative ions. However, with saturating glucose present there was a pH effect on the surface residue accessibility. Titrations in 55 vol.% glycerol suggest the presence of transient channels (not just holes) in the hexokinase structure, which allows penetration of the protein by solution. Consequently, the buried tryptophan residue is quenched more strongly by dissolved acrylamide than is attributable to diffusion of quencher through the protein matrix.

Acrylamides↗
PubMed1980

Effects of free magnesium and alkali ions on the conformation and glucose-binding strength of yeast hexokinase isozymes.

Titrations of the tryptophan fluorescence of yeast hexokinase (ATP:D-hexose 6-phosphortransferase, EC 2.7.1.1.) isozymes P-I (A) and P-II (B) were performed with Mg2+, Li+, Na+ and K+ as titrant in absence and in presence of glucose, and vice versa, at pH 8.3 and 5.5 at 20 degrees C. Mg2+ quenches the fluorescence of surface tryptophan primarily and does so by producing a conformational change which alters the microenvironment of the tryptophan. For both isozymes Mg2+ exerts a specific ion effect, i.e. significantly larger than the ionic strength (I) effect, which enhances the glucose quenching by causing a conformation change which increases the glucose-binding constant. For the P-I isozyme glucose binding exhibits positive cooperativity at both pH 8.3 and 5.5 when the ionic strength (I) is low, i.e. significantly larger than the ionic strength (I) effect, which enhances the glucose quenching by causing a conformation change which increases the glucose-binding constant. For the P-I isozyme glucose binding exhibits positive sooperativity at both pH 8.3 and 5.5 when the ionic strength (I) is low, i.e. 0.04 or less, regardless of which of the above four cations is present. For P-II, however, glucose binding is non-cooperative at pH 8.3 regardless of I or the cation species and at pH 5.5 and low I with K+ or Mg2+ as the predominant cation present, but there is apparent negative cooperativity at pH 5.5 and low I when Na+ or Li+ predominates. These results are discussed in terms of known structural characteristics of the isozymes.

Binding Sites↗
PubMed1978

Fluorescence-quenching study of glucose binding by yeast hexokinase isoenzymes.

A study of the effect of varying ionic strength on the glucose-induced quenching of tryptophan fluorescence of hexokinase isoenzymes A(P-I) and B(P-II) was carried out at pH 8.3 and pH 5.5. At p/ 8.3 both isoenzymes gave apparently linear Scatchard-type data plots even with protein concentrations and ionic strengths for which both dimeric and monomeric forms of hexokinase coexist in signiciant amounts. Taking inco account a 1% accuracy in the experimental measurements, we concluded that the intrinsic dissociation constants K(M) and K(D), for the binding of glucose to the monomeric and dimeric forms of HkB, are within a factor of two of each other, i.e. K(D)/K(M) less than or equal to 2. The values of K(M), estimated from the apparent K, were so greatly influenced by ionic strength that it is clear that it is meaningless to compare K(M) and K(D) values measured at different ionic strengths as has been done in the literature. Curvature in the pH 5.5. fluorescence-quenching plots for relatively low ionic strengths demonstrates cooperativity for glucose-binding to the dimer, positive for HkA but negative for HkB. In contrast, the binding is relatively non-cooperative at high ionic strength at this pH. These results were attributed to the well known effect of salt-neutralization of side chain electrical charges on the flexibility and compactness of proteins.

Glucose↗