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Biomedical subjects

J Lazar

Publications and source records attributed to J Lazar.

At least 19 recordsLinked to original sources
PubMed1997

Active repression by thyroid hormone receptor splicing variant alpha2 requires specific regulatory elements in the context of native triiodothyronine-regulated gene promoters.

Structural requirements for the inhibitory action of thyroid hormone receptor splicing variant alpha2 (TR alpha2) on T3/TRbeta1-mediated transactivation were investigated in native promoters of two T3-regulated genes: the brain-specific myelin basic protein (MBP) and the housekeeping malic enzyme (ME). T3/TRbeta1 transactivation of MBP256-chloramphenicol acetyl transferase (CAT) and ME315-CAT constructs was inhibited and unaffected by TR alpha2, respectively. In electrophoretic mobility shift assays, TR alpha2 bound MBP-thyroid response element (TRE) as a monomer but failed to interact with ME-TRE. Mutations of ME-TRE allowed TR alpha2 binding but not inhibition of T3/TRbeta1-mediated transactivation. In the context of the MBP promoter, replacement of MBP-TRE with ME-TRE or exchange of MBP TATA-like box with the ME GC-rich region spanning the transcription start site abolished TR alpha2 dominant negative action. Simultaneous introduction of both MBP-TRE and MBP TATA-like box in the context of ME promoter, however, triggered TR alpha2 inhibition of T3/TRbeta1 transactivation, indicating that these regulatory elements are necessary, but not individually sufficient, to mediate TR alpha2 dominant negative activity. Functional studies at low TR alpha2/TRbeta1 ratios revealed that binding to TRE facilitates TR alpha2 dominant negative action while prevention of DNA interaction by altering TR alpha2 P-box structure preserved TR alpha2 inhibitory effect, although with lower potency. In conclusion, the results suggest that, in native promoters of T3-regulated genes, a dual molecular mechanism, with DNA-binding dependent and DNA-binding independent components, underlies TR alpha2 dominant negative activity.

Animals↗
PubMed1995

The N-terminal region (A/B) of rat thyroid hormone receptors alpha 1, beta 1, but not beta 2 contains a strong thyroid hormone-dependent transactivation function.

In this study we have investigated the role of the N-terminal region of thyroid hormone receptors (TRs) in thyroid hormone (TH)-dependent transactivation of a thymidine kinase promoter containing TH response elements composed either of a direct repeat or an inverted palindrome. Comparison of rat TR beta 1 with TR beta 2 provides an excellent model since they share identical sequences except for their N termini. Our results show that TR beta 2 is an inefficient TH-dependent transcriptional activator. The degree of transactivation corresponds to that observed for the mutant TR delta N beta 1/2, which contains only those sequences common to TR beta 1 and TR beta 2. Thus, TH-dependent activation appears to be associated with two separate domains. The more important region, however, is embedded in the N-terminal domain. Furthermore, the transactivating property of TR alpha 1 was also localized to the N-terminal domain between amino acids 19 and 30. Using a coimmunoprecipitation assay, we show that the differential interaction of the N terminus of TR beta 1 and TR beta 2 with transcription factor IIB correlates with the TR beta 1 activation function. Hence, our results underscore the importance of the N-terminal region of TRs in TH-dependent transactivation and suggest that a transactivating signal is transmitted to the general transcriptional machinery via a direct interaction of the receptor N-terminal region with transcription factor IIB.

3T3 Cells↗
PubMed1995

Public reporting of performance measures in home care.

BACKGROUND: In 1992 DependiCare Home Health, Inc (Broadview, Ill), a 62-employee home medical equipment/respiratory therapy (HME) business in the Chicago metropolitan area, discovered that managed care organizations need quantifiable data from vendors in the form of measurements or outcomes. In response to this need, DependiCare developed its "Under the Microscope" program. This program provides quarterly reports (starting in April 1994) on service efficiency, patient satisfaction, and outcome statistics to referral sources, including physicians, discharge planners, and hospital executives. MEASUREMENTS: Performance measures, which represent information from DependiCare's internal operations, can be viewed as the company's quarterly report card. Areas reported on include target-time performance, same-day and under-two-hour delivery, patient (and referral source) satisfaction, equipment breakdown, and fillrate statistics. Outcome statistics include discontinuation of service by diagnosis and number of months on oxygen by diagnosis. USE OF RESULTS: Measurements help to identify weaknesses that need to be addressed by organizational or operational changes, as well as to uncover strengths that can be capitalized on for sales and marketing. Hospital-based discharge planning departments, a substantial referral source, most often use the Under the Microscope program to justify referring patients to DependiCare. Little is known about managed care customers' use of the data. CONCLUSIONS: In the long term, an integrated, automated way to track individual patients across the continuum of care from the physician, to the hospital, and to home care is needed. A centralized database of patient experience, including outcomes, could assist in health care decision making.

Capitation Fee↗
PubMed1994

A role for intronic sequences on expression of thyroid hormone receptor alpha gene.

We have cloned and characterized the organization of the rat thyroid hormone receptor alpha (THR) gene. Multiple transcription start sites were mapped by RNA primer extension analyses. The promoter of the rat THR alpha gene does not contain a TATA or CAAT box. Deletion analyses of the 5' region of THR alpha gene and transfection assays, using NIH3T3 and NG108-15 cells, revealed that the sequences from -137 to +205 (+205 resides in the first intron) are necessary for efficient expression of this gene. This region contains two positively acting elements, the sequence -137 to -60 upstream from the major start of transcription and three copies of an AGG sequence located in the first intron. In contrast, two octamer-binding motifs in the first intron function as the negative regulatory elements. Gel mobility shift assays showed that the purine-rich sequence and the octamer-binding motifs bind to a protein(s) present in NIH3T3 and NG108-15 cells, the recipients in transient transfection assays. Genomic sequence comparison of THR alpha and beta revealed the presence of the purine-rich track in both genes, while the octamer-binding motifs were found only in the alpha gene. These results might explain the differential regulation of THR alpha and beta gene expression previously noted.

3T3 Cells↗
PubMed1994

The stability of tachistoscopic measures of hemispheric specialization.

Two-week test-retest reliabilities were determined for two tachistoscopic tasks, consonant-vowel-consonant trigrams and dot location, in 48 right-handed university students. Both visual field and laterality scores were examined. Analysis of variance showed no significant main effects or interactions of session for either task, indicating stability of mean performance and laterality scores. Likewise, grouping subjects as "high" or "low" by median laterality scores showed concordance across sessions for both tasks. Test-retest correlations were moderately high for all verbal task measures and for visual field scores for the dot location test. However, laterality indices for dot location showed low stability despite comparable within-session reliabilities of laterality scores for the two tasks. These findings suggest stability of group means and subgroups for verbal and dot location tachistoscopic measures. However, the degree to which individual scores are predictable from one session to the next differs between the two tasks.

Adult↗
PubMed1993

Early thyroid hormone treatment in rats increases testis size and germ cell number.

By means of in vivo and in vitro approaches, we studied the effect of thyroid hormone on postnatal development of rat testis. T3 treatment in neonatal rats is associated with an increase of testis size of about 60%, compared to coeval controls. Increased number of both Sertoli and germ cells and enlarged diameter of seminiferous cords were found in hyperplastic testes. In the T3-treated group, TSH serum levels were low and a slight increase of FSH was found. In vitro treatment of neonatal testis fragments by 10(-7) M T3 for 3 days increased the number of gonocytes (P < 0.001 vs control) and decreased the percentage of degenerating germ cells (P < 0.001 vs control). In the adult testis, both in vivo and in vitro treatments with thyroid hormone did not induce morphological modifications, thus demonstrating that the critical window of thyroid hormone effectiveness coincides with the prepuberal period. Since thyroid hormone stimulates Sertoli cells to secrete growth factors and nutrients for germ cell development, we suggest that the increased testicular size and germ cell number following the T3 treatment is mediated by a direct hormonal effect on the somatic cell of the seminiferous epithelium.

Animals↗
PubMed1992

[Structural basis of appendiceal function in rabbits].

Enzymo-, immuno- and lactin-histochemical methods were used to study the structure of the rabbit appendix wall. The value of some structural components in the function of this part of the intestine is discussed. Some findings were documented electronmicroscopically. In addition to its resorptive function, the rabbit appendix is equipped with a potent defense mechanism against adverse environmental effects of the appendix content. Individual structures of this defensive barrier are closely characterized with regard to cellular equipment and possibilities of its morphological identification.

Animals↗
PubMed1987

Serum angiotensin converting enzyme activity in evaluation of patients with liver disease.

This study was undertaken to evaluate angiotensin converting enzyme activity in patients with liver disease, and to explore its relationship to thyroid function in patients with liver disease. Serum angiotensin converting enzyme activity and thyroid hormone levels, determined in 79 patients with intrahepatic-type liver disease and 18 patients with extrahepatic biliary obstruction, were compared with values in 129 euthyroid controls. Serum angiotensin converting enzyme activity was higher in intrahepatic disease than in extrahepatic obstruction, but statistically significant only for acute intrahepatic disease. In the patients studied, high serum angiotensin converting enzyme activity (22 units/ml or more) virtually excluded extrahepatic biliary obstruction, with a negative predictive value of 94 percent. Low serum angiotensin converting enzyme activity had a positive predictive value for extrahepatic obstruction of only 67 percent. Increased angiotensin converting enzyme activity could not be explained as a function of enhanced thyroid activity. Serum angiotensin converting enzyme activity may be useful in separating patients with intrahepatic liver disease from those with extrahepatic obstruction.

Cholestasis, Extrahepatic↗
PubMed1985

Liquid-chromatographic assay of cimetidine in plasma and gastric fluid.

In this micro-scale method for liquid-chromatographic measurement of cimetidine in 250-microL volumes of plasma or gastric fluid, a combination of organic- and aqueous-phase extractions, and protonation of the internal standard and cimetidine, enabled us to detect 2.0 ng of cimetidine on the column. We also used a radial compression module, which reduced the retention times for cimetidine and the internal standard to only 2.78 and 2.00 min. The speed and sensitivity of this method facilitates analysis of large numbers of samples.

Chromatography, High Pressure Liquid↗
PubMed1982

Age, response complexity, and target consistency in visual search.

Adult age differences in visual search were examined under manipulations of target set consistency (fixed versus varied), response complexity (2 versus 4 sorting categories), display size (1, 4, or 8 letters/card), and sessions (2). Mean card sorting times of 20 young (mean = 22 years) and 20 elderly (mean = 62 years) adults were compared. Significant main effects of age, complexity, consistency, sessions, and display size were obtained. A consistent target set facilitated search independent of response complexity. As predicted, significant interactions indicated that age differences in search were eliminated under the fixed set procedure but not under the varied set procedure.

Adolescent↗
PubMed1980

An inhibitor of arachidonic acid metabolism stimulates luteinizing hormone (LH) release from cultured pituitary cells.

5, 8, 11, 14 eicosatetraynoic acid ("ETYA", Roche 3-1428) is a competitive inhibitor of arachidonic acid metabolism. It effectively inhibits the action of both the lipoxygenases and the fatty acid cyclooxygenases both of which utilize arachidonic acid as a substrate. In the present work, we have shown that ETYA stimulates luteinizing hormone (LH) release from cultured pituitary cells (ED50 = 10 micrograms/ml). Stimulation is not due to contaminants present in the preparation, since highly purified ETYA (characterized by GC-MS) stimulates release, while contaminants removed by silicic acid chromatography do not. In addition, neither oxidized solutions of ETYA nor arachidonic acid itself stimulate LH release. ETYA stimulated release is dose dependent and is inhibited by ions which antagonize Ca2+ action. The observation that neither indomethecin (10, 100 micrograms/ml) nor meclofenamate (1.0, 10 micrograms/ml) stimulate LH release suggests that the effect of ETYA cannot be explained by an action on cyclooxygenase. The action of ETYA may be mediated either via an effect on lipoxygenase or through some nonspecific action (such as altered membrane fluidity).

5,8,11,14-Eicosatetraynoic Acid↗