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Biomedical subjects

J Leonard

Publications and source records attributed to J Leonard.

At least 19 recordsLinked to original sources
PubMed1992

The LIM family transcription factor Isl-1 requires cAMP response element binding protein to promote somatostatin expression in pancreatic islet cells.

Many eukaryotic genes are regulated by cAMP through a conserved cAMP response element (CRE). Here we show that, in the pancreatic islet cell line Tu6, a well-characterized CRE in the somatostatin gene does not provide cAMP responsiveness but functions as an essential element for its basal activity. DNA-binding and functional analyses indicate that the cAMP-responsive factor CREB regulates somatostatin expression in these cells without requirement for phosphorylation at the protein kinase A-regulated Ser-133 phosphorylation site. In addition to the CRE site, cell-specific expression of the somatostatin gene requires a second promoter element, which binds the recently characterized LIM family protein Isl-1. Thus, Isl-1 and CREB appear to synergize on the somatostatin promoter to stimulate high-level expression in Tu6 cells. The ability of CREB to function in a phosphorylation-independent manner suggests a mechanism by which this protein can regulate gene transcription.

Base Sequence↗
PubMed1992

Structure-function studies of the epidermal growth factor domains of human thrombomodulin.

Structure-function relationships in the 6 epidermal growth factor-like domains of human thrombomodulin (TME, residues 227-462) were studied by deletion mutagenesis. Purified and characterised proteins were used for kinetic studies. Deletion of EGF1, EGF2 and residues 310-332 in EGF3 had no effect on thrombin binding (Kd) or on kcat/KM for protein C activation by the thrombin-thrombomodulin complex. Deletion of the rest of EGF3 and the interdomain loop between EGF3 and EGF4 had no effect on Kd but decreased kcat/KM to 10% of TME. Deletion of residues 447-462 of EGF6 had no effect on kcat/KM but increased Kd for thrombin approximately 6-fold. Thus, the region 333-350 in EGF3-4 is critical for protein C activation by the thrombin-thrombomodulin complex and the region 447-462 in EGF6 is critical for thrombin binding.

Base Sequence↗
PubMed1992

Effects of anesthesia and stimulus intensity on posterior tibial nerve somatosensory evoked potentials.

Under anesthesia peak latencies occurring up to 75 milliseconds after stimulus onset upon somatosensory evoked potential testing of the somatosensory evoked potential testing of the posterior tibial nerve were not affected by stimulus intensity (between 5 and 19 ma) or by length of time under isoflurane and nitrous oxide up to over 2 hours. When pre- and postoperative tests on patients who were not under anesthesia were compared with results under anesthesia, no significant latency differences were found in relation to stimulus intensity for peaks N30, P40 and N50. For peaks P60 and N75, however, significantly increased latencies were seen during anesthesia, more pronounced and consistent for N75. Amplitudes, however, were affected by both stimulus intensity and anesthesia duration. A curvilinear relationship was found during early anesthesia. Maximum amplitudes were found at 7 or 11 ma stimulus intensity levels, depending upon which peak was analyzed, with lesser amplitudes occurring at both lower and higher stimulus intensity levels. Stimulus intensity and anesthesia interacted such that maximum amplitude occurred, in general, at 11 ma after short duration anesthesia (6') and at 7 ma after long duration anesthesia (125'). Under long duration anesthesia amplitudes were significantly diminished, mostly at the 11 ma intensity level. At 15 and 19 ma intensity levels peak amplitudes remained relatively constant regardless of anesthesia duration and therefore are the intensities to use to monitor changes during prolonged surgeries. When preoperative during prolonged surgeries. When preoperative and postoperative tests were compared to tests under anesthesia, there was a decrease in amplitude under anesthesia, greater for long than short duration anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of stimulus intensity on posterior tibial nerve somatosensory evoked potentials.

Relationships between stimulus intensity and peak latencies and amplitudes in posterior tibial nerve somatosensory evoked potential patterns were evaluated in ten healthy subjects. Eight intermediate latency peaks between 30 and 125 milliseconds (ms) after stimulus onset and seven amplitudes were analyzed. In general, there was a decrease in latency with each increase in stimulus intensity over a five step intensity range between 5 and 19 milliamps (mA) for most peaks. Similarly, increases in amplitudes generally occurred with increases in stimulus intensity for most peaks. Later peaks N105 and P115 as well as amplitudes P90-N105 and N105-P115 were least sensitive to stimulus intensity changes. The greatest changes in peak latency and amplitude occurred as stimulus intensity was increased from 7 to 11 mA. Beyond 11 mA relatively little change was observed in either peak latencies or amplitudes. Under anesthesia, by contrast, there was no stimulus intensity-peak latency interaction and beyond 11 mA there were decreases in amplitudes. Possible reasons for these findings are discussed.

Adult↗
PubMed1992

Respiratory failure and cor pulmonale associated with tracheal mucoid accumulation from a SCOOP transtracheal oxygen catheter.

Transtracheal oxygen (TTO) delivery for patients with chronic hypoxemia has been used increasingly since its introduction in 1982. Most complications have been relatively minor and usually occur in conjunction with catheter placement. This report describes two patients with long-term catheter use who developed increasing respiratory failure and cor pulmonale, at least in part, due to a large tracheal mucus plug.

Airway Obstruction↗
PubMed1991

Monoclonal anti-idiotypic antibodies to human melanoma-associated proteoglycan antigen: generation and characterization of anti-idiotype antibodies.

We have characterized a number of monoclonal anti-idiotype antibodies (mAb2s) made against a monoclonal antitumor antibody, MEM136. The monoclonal antibody 1 (mAb1) MEM136 recognizes an epitope on human melanoma-associated proteoglycan and blocks melanoma cell interaction with basement membrane components in vitro. The anti-idiotype antibodies (Ab2s) made against MEM136 each cross-inhibited, to varying degrees, their binding to MEM136. Thus, the mAb2s recognized overlapping idiotopes on MEM136. In an attempt to identify potential internal image candidates we set up a cell migration inhibition assay. In this assay, migration of melanoma-associated proteoglycan-positive Colo38 cells was determined through a membrane barrier impregnated with Matrigel, which is composed of extracellular matrix components, i.e., collagen type IV, heparan sulfate, and laminin. Interestingly, only Ab2s IM06 and IM32 inhibited melanoma cell migration. Additional studies indicate that of eight mAb2s tested, only IM32 and IM06 induced anti-MPG responses in rabbits. The possibility that IM32 and IM06 bear images of melanoma cell surface-associated proteoglycan epitopes is discussed.

Antibodies, Anti-Idiotypic↗
PubMed1991

Acarex test correlates with monoclonal antibody test for dust mites.

Forty-two dust samples from the homes of patients having positive mite skin tests were tested by both monoclonal antibody and Acarex techniques. A Spearman's correlation coefficient of 0.85 (p = 0.0001) was found. The Acarex test is simple to use and is much less expensive than the monoclonal antibody method. The use of either method may enhance patient compliance with mite-control instructions and may prove crucial to the effective use of miticides in infested homes.

Animals↗
PubMed1991

Variable role of the long terminal repeat Sp1-binding sites in human immunodeficiency virus replication in T lymphocytes.

The long terminal repeat (LTR) of the human immunodeficiency virus (HIV) contains three binding sites for the transcriptional factor Sp1. In order to investigate the role that the Sp1-binding sites play in regulation of HIV replication, we have introduced a deletion of all three Sp1-binding sites into the LTR of an infectious molecular clone of HIV. Viral stocks have been prepared from this mutant virus, designated dl-Sp, and these stocks have been used to study its replicative ability in human T cells. The dl-Sp virus replicated efficiently in MT4 cells and in phytohemagglutinin-stimulated human peripheral blood lymphocytes, but it replicated poorly and with delayed kinetics in A3.01 (CEM) T cells unless those cells had been treated with the cytokine tumor necrosis factor alpha. Gel retardation assays to study the levels of DNA-binding proteins present in these cells showed that NF-kappa B activity could be detected in the nuclei of MT4 cells but not in A3.01 cells unless they had been treated with tumor necrosis factor alpha. Thus, the presence of NF-kappa B activity appeared to be required for efficient replication of an HIV whose LTR Sp1-binding sites had been deleted. This suggests that NF-kappa B can functionally compensate for Sp1 in activating HIV replication. The HIV LTR is therefore similar to the promoter-enhancer units of other viruses in that it is composed of multiple functional elements that may contribute differently to viral replication depending on the levels of DNA-binding proteins present in the target cells.

Animals↗
PubMed1991

Characterization of motifs which are critical for activity of the cyclic AMP-responsive transcription factor CREB.

Cyclic AMP mediates the hormonal stimulation of a number of eukaryotic genes by directing the protein kinase A (PK-A)-dependent phosphorylation of transcription factor CREB. We have previously determined that although phosphorylation at Ser-133 is critical for induction, this site does not appear to participate directly in transactivation. To test the hypothesis that CREB ultimately activates transcription through domains that are distinct from the PK-A site, we constructed a series of CREB mutants and evaluated them by transient assays in F9 teratocarcinoma cells. Remarkably, a glutamine-rich region near the N terminus appeared to be important for PK-A-mediated induction of CREB since removal of this domain caused a marked reduction in CREB activity. A second region consisting of a short acidic motif (DLSSD) C terminal to the PK-A site also appeared to synergize with the phosphorylation motif to permit transcriptional activation. Biochemical experiments with purified recombinant CREB protein further demonstrate that the transactivation domain is more sensitive to trypsin digestion than are the DNA-binding and dimerization domains, suggesting that the activator region may be structured to permit interactions with other proteins in the RNA polymerase II complex.

Amino Acid Sequence↗
PubMed1991

Alcoholics Anonymous-Narcotics Anonymous model inpatient treatment of chemically dependent adolescents: a 2-year outcome study.

Many hospital and residential chemical dependency treatment facilities utilize Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) principles and practices in therapeutic programming. Although well-known and broadly endorsed and supported, such AA/NA approaches have received little research attention especially in regard to chemically dependent adolescents. The present study examined chemical usage and social-civil-productive functioning in 157 male and female chemically dependent adolescents at 6, 12 and 24 months after leaving an AA/NA-based treatment program. Results revealed that both treatment completers and noncompleters (those who left treatment prematurely against professional/medical advice) demonstrated less chemical use after their respective hospitalizations than before. Although significantly higher percentages of both male and female treatment completers were found abstinent/essentially abstinent at 6 months post discharge in contrast to noncompleters, abstinence rates, particularly for male subjects, declined sharply by 1 and 2 years after treatment. Results indicated that the AA/NA model is a promising approach in treating chemically dependent adolescents, but that much attention to relapse prevention methods is necessary.

Adolescent↗
PubMed1991

Cost-effectiveness of hepatitis B screening in a mental health institution.

In 1982, the Ohio Department of Health Screening established guidelines for hepatitis B screening and vaccination for intermediate mental health care facilities. The present study was developed to evaluate the cost-effectiveness of these guidelines. Data from an intermediate mental health care institution in Champaign/Urbana, Illinois, were used. The analysis considered the direct costs and benefits accrued over a 3-year period and a range of transmission rates. At a 3-year transmission rate of 0.030, the screening and vaccination policy cost $7300 per case of hepatitis B avoided (or $345,800 per hepatitis B fatality avoided). At a more likely 3-year transmission rate of 0.271, the screening and vaccination policy cost $300 per case of hepatitis B avoided (or $12,100 per hepatitis B fatality avoided). Either way, the active prevention policy compares very well with the amounts of money spent by the US Government on other life-saving programs. A general cost-effectiveness model is given that can be adapted for institution-specific analyses at other mental health care facilities.

Cost-Benefit Analysis↗
PubMed1990

[Fetal macrosomia in a diabetic mother].

Foetal macrosomia is arbitrarily defined as an excessive weight for the gestational age, was found to be present in 36 p. 100 of 43 diabetic pregnancies. This finding may indicate incomplete normalization of maternal metabolic control despite the use of new forms of insulin delivery systems, such as insulin pumps. However, in our series the macrosomia was usually moderate and without consequences on the foetal outcome. The levels of insulin, but not those of the insulin-like growth factor (IgF1), were increased in the umbilical cord blood of macrosomic newborns of diabetic mothers. Cardiac septum hypertrophy correlated with maternal glycosylated haemoglobin levels better than with macrosomia. We therefore suggest that in all diabetic pregnancies the cardiac septum thickness should be measured in utero by sonocardiography.

Adult↗