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Biomedical subjects

L Field

Publications and source records attributed to L Field.

At least 19 recordsLinked to original sources
PubMed1997

Inhibition of multiple phases of human immunodeficiency virus type 1 replication by a dithiane compound that attacks the conserved zinc fingers of retroviral nucleocapsid proteins.

The human immunodeficiency virus type 1 (HIV-1) nucleocapsid p7 protein contains two retrovirus-type zinc finger domains that are required for multiple phases of viral replication. Chelating residues (three Cys residues and one His residue) of the domains are absolutely conserved among all strains of HIV-1 and other retroviruses, and mutations in these residues in noninfectious virions. These properties establish the zinc finger domains as logical targets for antiviral chemotherapy. Selected dithiobis benzamide (R-SS-R) compounds were previously found to inhibit HIV-1 replication by mediating an electrophilic attack on the zinc fingers. Unfortunately, reaction of these disulfide-based benzamides with reducing agents yields two monomeric structures (two R-SH structures) that can dissociated and no longer react with the zinc fingers, suggesting that in vivo reduction would inactivate the compounds. Through an extensive drug discovery program of the National Cancer Institute, a nondissociable tethered dithiane compound (1,2-dithiane-4,5-diol, 1,1-dioxide, cis; NSC 624151) has been identified. This compound specifically attacks the retroviral zinc fingers, but not other antiviral targets. The lead compound demonstrated broad antiretroviral activity, ranging from field isolates and drug-resistant strains of HIV-1 to HIV-2 and simian immunodeficiency virus. The compound directly inactivated HIV-1 virions and blocked production of infectious virus from cells harboring integrated proviral DNA. NSC 624151 provides a scaffold from which medicinal chemists can develop novel compounds for the therapeutic treatment of HIV infection.

Anti-HIV Agents↗
PubMed1996

Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells.

A novel member of the winged helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis, was isolated and characterized. Putative translation of the complete cDNA revealed the winged helix DNA binding domain to be centrally located within the protein, with regions on either side that contain known transcriptional regulatory motifs. Extensive Northern analysis of Genesis found that the message was exclusively expressed in embryonic stem cells or their malignant equivalent, embryonal carcinoma cells. The Genesis transcript was down-regulated when these cells were stimulated to differentiate. DNA sequences that Genesis protein would interact with were characterized and were found to contain a consensus similar to that found in an embryonic stem cell enhancer sequence. Co-transfection experiments revealed that Genesis is a transcriptional repressor. Genesis mapped to mouse chromosome 4 in a region syntenic with human chromosome 1p31, a site of nonrandom abnormalities in germ cell neoplasia, neuroblastoma, and acute lymphoblastic leukemia. Genesis is a candidate for regulating the phenotype of normal or malignant embryonic stem cells.

Amino Acid Sequence↗
PubMed1993

High PSA.

Explore the source record for details and available documents.

Biomarkers, Tumor↗
PubMed1992

Predisposing factors for severe, uncontrolled hypertension in an inner-city minority population.

BACKGROUND: Hypertensive emergency and urgent hypertension are the most severe forms of uncontrolled hypertension and are now seen predominantly in poor, minority populations. We studied the characteristics of the medical care received by patients with these conditions in order to identify risk factors for severe, uncontrolled hypertension. METHODS: Using a case-control study design, we interviewed 93 patients with severe, uncontrolled hypertension who presented in the hospital emergency room and 114 control patients with hypertension; both groups were seen at two New York City hospitals from 1989 through 1991. All the patients were black or Hispanic. Multiple logistic-regression models were used to adjust for age, sex, race or ethnic background, education, smoking status, alcohol-related problems, and use of illicit drugs during the previous year. RESULTS: After additional adjustment for lack of health insurance, severe, uncontrolled hypertension was found to be more common among patients who had no primary care physician (adjusted odds ratio, 3.5; 95 percent confidence interval, 1.6 to 7.7) and among those who did not comply with treatment for their hypertension (adjusted odds ratio, 1.9; 95 percent confidence interval, 1.4 to 2.5). Lack of health insurance was marginally associated with severe, uncontrolled hypertension (adjusted odds ratio, 1.9; 95 percent confidence interval, 0.8 to 4.6) after adjustment for lack of a primary care physician and noncompliance with antihypertensive treatment. Patients without a primary care physician and without health insurance were more likely to have their blood pressure checked and receive prescriptions for blood-pressure medications in emergency rooms than in physicians' offices or clinics. CONCLUSIONS: Characteristics of both the health care system and patients' behavior are associated with severe, uncontrolled hypertension. Improving access to primary care physicians, through health insurance or other means, may be an effective strategy for improving control of hypertension in disadvantaged minority populations.

Adult↗
PubMed1992

The effects of common movement and spatial separation on position- and motion-based judgements of relative movement.

When common movement is superimposed on relative movement (changes in separation between two dots), relative movement thresholds increase nonlinearly as a function of initial dot separation. For large separation (greater than 2.0 deg), thresholds increase gradually with increased separation. It is shown that this reflects judgments based on perceived relative motion. For small separations (less than 2.0 deg), thresholds increase sharply with increased separation. It is shown that this reflects judgments based on perceived changes in relative position. Evidence is presented that superimposed common movement reduces sensitivity to relative movement by reducing sensitivity to relative motion. This provides a "window", in the range of small dot separations, for relative movement judgements to be based on the perception of changes in relative position, even though motion is perceived for individual dots.

Humans↗
PubMed1992

Correlates of nonadherence to hypertension treatment in an inner-city minority population.

OBJECTIVE: Adherence to treatment is a key factor in achieving blood pressure control among hypertensives. We examined correlates of nonadherence to hypertension treatment in an inner-city minority population. METHODS: Subjects (n = 202) were interviewed as part of a case-control study of severe, uncontrolled hypertension conducted in two New York City hospitals in 1989-91. All subjects were African American or Hispanic. Self-reported nonadherence to drug treatment for hypertension was measured using a five-item scale, and the sample was dichotomized as more (n = 87) or less (n = 115) adherent. Multiple logistic regression analysis was used to adjust for demographic and other covariates. RESULTS: Nonadherence was associated with having blood pressure checked in an emergency room (adjusted odds ratio [OR] = 7.9; 95% confidence interval [CI] = 1.75, 35.77; P < .01), lack of a primary care physician (adjusted OR = 2.9; 95% CI = 1.37, 6.02; P < .01), current smoking (adjusted OR = 2.4; 95% CI = 1.10, 5.22; P = .03), and younger age (adjusted OR = 1.03, 95% CI = 1.00, 1.06; P = .03). CONCLUSIONS: Changing the locus of care for hypertension from emergency rooms to primary care physicians may improve adherence to hypertension treatment in minority populations.

Adult↗
PubMed1989

Evidence for the abstractive encoding of superficial position information in visual patterns.

When presented a series of patterns inside a frame, subjects unintentionally retained information concerning the frame-relative location of the elements composing the patterns; they could use this superficial information to estimate the frequency with which the elements occurred at various locations within the frame. There were two aspects of the results that supported the hypothesis that this superficial element-location information was abstractively encoded and, therefore, retrievable independent of the patterns comprising the elements: (1) Correlations between actual and estimated frequency remained significant after the effects of pattern recall were partialled out, and (2) correlations were enhanced by assuming that the frequency estimate for each location was affected by the imprecise coding of position for elements falling in surrounding locations. Additional experiments indicated that an orienting task emphasizing pattern recall resulted in very inaccurate estimation of element-location frequency, and intentional instructions improved the precision of position coding for individual elements.

Adult↗
PubMed1986

Potential antiradiation drugs containing no nitrogen, and related compounds.

Capabilities are reported of di- and higher sulfides (RSnR') terminated by sulfinate functions [-S(O)O-] for protecting mice against otherwise lethal effects of ionizing radiation. With the use of congeners, structure-activity correlations are developed for the effects of esterification of the sulfinate function, of changing the length of the chain of sulfur atoms, of reduction to a mercapto sulfinate, and of changing the substituents R and R' to chiral and other types of groups. Neither a trisulfide nor a sulfinate by itself was significantly radioprotective. The key requirement for radio-protection in the series appears to be the presence of a sulfur function (-Sn-) from which a thiol can be engendered by a neighboring-group effect of an electron-donating group; sulfoxide functions may afford alternatives to sulfinate functions as such neighboring groups. The relevance of structure-activity relations to the chemical and biological mechanisms involved in the radioprotective activities is discussed.

Animals↗
PubMed1985

A linkage analysis of the Gm locus and multiple sclerosis.

We conducted linkage analyses of immunoglobulin G heavy chain marker (Gm) phenotypes and multiple sclerosis (MS) in 30 families, each having at least two first-degree relatives with definite/probable MS. These families yielded positive evidence for linkage to human leukocyte antigen (HLA) loci in previous analyses. In the present analysis, however, the results for Gm were negative. Most lod scores were negative, particularly at the smaller recombination values (theta). We explored the possibility of heterogeneity by subgrouping our data on the basis of specific HLA types (A3, B7) and Gm types (Gm1, Gm1,2) within the pedigrees. The results were again negative with no substantial differences in estimates of theta between subgroups.

Gene Frequency↗
PubMed1985

Mutagenic and cell transformation activities of representative phosphorothioate esters in vitro.

Five alkyl and five aryl phosphorothioates are ranked relative to parathion in effectiveness as base-pair mutagens in the Ames mutagenic assay. Three in each series were mutagenic. Two commercial insecticidal phosphates, included for comparison, were mutagenic. The mutagenic phosphorothioates contained a strong electron-withdrawing and/or a good leaving group, together with two other groups small enough to permit nucleophilic attack by a biomacromolecule on the electrophilic phosphorus atom. All but one of the phosphorothioates [i.e., O,O,O-tris(2,2,2-trifluoro)ethyl phosphorothioate, VI] required metabolic activation for mutagenicity to be manifested; hence most of the phosphorothioates per se evidently are not ordinarily sufficiently electrophilic to be mutagenic but must instead be transformed to more electrophilic oxygen-containing products. In evaluation for cell-transformation properties, methyl parathion was inactive, in contrast to VI. The phosphorothioates that were novel were synthesized by formation of the phosphite from the appropriate alcohol or phenol, followed by reaction of the phosphite with sulfur.

Animals↗
PubMed1984

Thiono compounds. 4. In vitro mutagenic and antineoplastic activity of TEPA and thio-TEPA.

Tris (1-aziridinyl) phosphine oxide (TEPA) and tris (1-aziridinyl) phosphine sulfide (thio-TEPA) induced base pair mutations in the Ames mutagenic assay. Thio-TEPA required metabolic activation while TEPA was active without metabolic activation. Growth of a human vaginal carcinoma (A431), a human breast carcinoma (MDA-MB-231), and a human cervical carcinoma (HeLa) were inhibited in soft agar in vitro at concentrations which induced mutagenesis in the Ames Assay. A fourth line, JEG choriocarcinoma, was sensitive to the antigrowth properties of both drugs at concentrations below that which induced mutagenesis. These data suggest that as more antineoplastic agents become available, and as mean survival times increase, knowledge of the relative in vitro sensitivity of a patient's neoplasm to a specific antineoplastic drug (i.e., dose required for growth inhibition) as a function of its mutagenic index might be useful for prediction of clinical remission, as well as the risk of secondary neoplasm induction.

Antineoplastic Agents↗
PubMed1984

Influence of penicillamine and various analogs on matrix-induced bone formation in rats.

D-penicillamine and a variety of analogs have been tested for their ability to interfere with the various stages of bone development using a model for endochondral bone formation. At the highest dose tested (40 mg/rat/day), D-penicillamine inhibited mineralization, D-2-Amino-3-methyl-3-[(2-acetamidoethyl)dithio]butanoic acid (II), at a relatively low dose (10 mg/day), decreased the amount of insoluble collagen in skin, mesenchymal cell proliferation on Day 3, and inhibited bone formation on Day 14. Several other compounds tested, sodium 4-[(D-1, 1-dimethyl-2-amino-2-carboxyethyl)-dithio]butanesulfinate (IV), 2-acetamidoethyl-2-acetamidoethanethiolsulfonate (V), and sodium 4-mercaptobutanesulfinate trihydrate (VI), also inhibited osteogenesis on Day 14.

Animals↗
PubMed1984

Outbreak of illness due to volatilized asphalt coming from a malfunctioning fluorescent lighting fixture.

We investigated an outbreak of headache, eye irritation, sore throat, nasal congestion, and nausea in an office complex, ongoing for three months and regularly resolved upon leaving the building. Investigation suggested that the etiology of the illness was malfunctioning fluorescent light ballasts , which overheated and resulted in melting and volatilization of contained asphalt . Correction of the problem resulted in almost complete disappearance of symptoms within two weeks.

Eye Diseases↗