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J Lowry

Publications and source records attributed to J Lowry.

At least 19 recordsLinked to original sources

Sedation standards.

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Anesthesia, Dental↗

Alleles from chromosomes 1 and 3 of NOD mice combine to influence Sjögren's syndrome-like autoimmune exocrinopathy.

OBJECTIVE: NOD mice exhibit at least 2 overlapping autoimmune diseases: autoimmune endocrinopathy (Type I, insulin dependent diabetes) and autoimmune exocrinopathy (Sjogren's syndrome, SS). To date, 18 chromosomal regions have been identified that contribute to development of diabetes in NOD mice; however, genetic mapping of similar susceptibility loci for autoimmune exocrinopathy is just beginning. We investigated if these 2 autoimmune diseases share a genetic predisposition. METHODS: Congenic partner strains of NOD and C57BL/6 mice containing defined genetic intervals influencing susceptibility to diabetes (Idd) were screened for histological and biochemical markers for their effect on the development of SS-like disease. Saliva flow rates, protein concentration, amylase activity, and cysteine protease activity were evaluated. RESULTS: In contrast to the nonsusceptible parental C57BL/6 strain, C57BL/6.NOD Idd5 congenic partner strain, containing a genetic region derived from chromosome 1 of the NOD mouse, exhibited pathophysiological characteristics of autoimmune exocrinopathy. Replacement of individual diabetes susceptibility intervals Idd3, Idd5, Idd13, Idd1, and Idd9, as well as a combination of the Idd3, Idd10, and Idd17 intervals, with resistance alleles had little effect on development of autoimmune exocrinopathy. Conversely, NOD mice, in which the chromosome regions containing both Idd5 and Idd3 have been replaced by intervals derived from C57BL mice, exhibit a reduced pathophysiology associated with SS-like autoimmune exocrinopathy. CONCLUSION: Alleles on chromosomes 1 (Idd5) and 3 (Idd3) in combination appear to greatly influence susceptibility and resistance to development of autoimmune exocrinopathy. The association with certain Idd, but not other Idd loci, indicate that genetic overlap is present but probably not inclusive.

Alleles↗

Wide circulation.

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Health Policy↗

A competitive mechanism of CArG element regulation by YY1 and SRF: implications for assessment of Phox1/MHox transcription factor interactions at CArG elements.

In the promoters of many immediate early genes, including c-fos, CArG DNA regulatory elements mediate basal constituitive expression and rapid and transient serum induction. CArG boxes also occur in the promoters of muscle-specific genes, including skeletal alpha-actin, where it confers muscle-specific expression. These elements are regulated, at least in part, by the ubiquitous transcription factors serum response factor (SRF) and YY1. The homeobox transcription factor Phox1/MHox has also been implicated in regulation of the c-fos CArG element and is thought to function by facilitating SRF binding to DNA. Here, we provide in vitro and in vivo evidence that the mechanism of YY1 repression of CArG elements results from competition with SRF for overlapping binding sites. We describe in detail the binding sites of YY1 and SRF through serial point mutations of the skeletal alpha-actin proximal CArG element and identify a mutation that dramatically reduces YY1 binding but retains normal SRF binding. YY1 competes with SRF for binding to wild-type CArG elements, but not to this point mutant in vitro. This mutant is sufficient for muscle-specific expression in vivo but is much less sensitive to repression by YY1 overexpression. We utilized the YY1/SRF competition to address the role of Phox1 at these elements. Phox1 overexpression did not diminish YY1-mediated repression, suggesting that transcriptional activation by Phox1 does not result from enhanced SRF binding to these elements. These methods may prove to be useful for assessing interactions between other CArG element regulatory factors.

Actins↗

Acoustic neuroma: potential benefits of fractionated stereotactic radiosurgery.

BACKGROUND: Single-fraction radiosurgery of acoustic neuromas less than 3 cm in diameter is remarkable for high control but not infrequent incidence of facial and trigeminal neuropathy. Larger tumors treated surgically often result in deafness and facial neuropathy. Fractionated stereotactic radiosurgery was used in an effort to maintain effective therapy while minimizing toxicity of treatment. METHODS: The authors described 38 patients with acoustic neuromas, with age range 35-89 years (mean, 60 years). 2,000 cGy in divided weekly doses of 400 or 500 cGy was most commonly prescribed. Tumors > or = 3 cm (n = 16) received the 5 fraction schema. Mean tumor volume was 6.9 cm3, with range from 0.1 to 32.0 cm3. RESULTS: Median clinical follow-up was 27.1 months, while neuroimaging follow-up had a median of 16.3 months. All tumors were controlled. Of 23 tumors smaller than 3 cm, 14 (61%) decreased in size, and 9 showed cessation of growth. Thirteen of 16 (81%) large acoustic neuromas (3-5 cm) diminished in size. The remaining 3 showed cessation of growth. Median radiographic follow-up was 20 months, with a median clinical follow-up of 28 months. No patient developed fifth nerve symptoms after treatment nor did any patient require surgery for treatment failure. Only one had temporary seventh nerve palsy. CONCLUSION: Fractionated stereotactic radiosurgery offers a therapeutic approach producing high control rates while avoiding morbidity frequently seen after single-fraction radiosurgery or microsurgery.

Adult↗

The human GATA-6 gene: structure, chromosomal location, and regulation of expression by tissue-specific and mitogen-responsive signals.

GATA factors constitute a family of transcriptional regulatory proteins expressed with distinct developmental and tissue-specific profiles and thought to regulate cell-restricted programs of gene expression. Here we describe the molecular cloning, chromosomal location, and transcription of the human GATA-6 gene. The GATA-6 cDNA encodes a predicted 449-amino-acid protein, which is highly conserved among vertebrates, and includes the two adjacent zinc-finger/basic domains characteristic of the GATA factor family. GATA-6 maps to human chromosome 18q11.1-q11.2 by fluorescence in situ hybridization. The gene is transcribed in a pattern overlapping that of GATA-4. Transcripts for both of these genes are prominent in heart, pancreas, and ovary, but only GATA-6 mRNA is found in lung and liver. GATA-6 transcripts are also detected in cultures of human and rat vascular smooth muscle cells (VSMCs). In VSMCs, GATA-6 transcripts are down- regulated when quiescent cultures are stimulated to proliferate in response to mitogen activation. These data demonstrate that GATA-6 is subject to both tissue-specific and mitogen-responsive regulatory signals. GATA-6 is a prime candidate for a gene that might regulate the differentiative state of VSMCs.

Amino Acid Sequence↗

Arterial gene transfer for therapeutic angiogenesis in patients with peripheral artery disease.

The age-adjusted prevalence of peripheral arterial disease (PAD) in the U.S. population has been estimated to approach 12%. The clinical consequences of occlusive peripheral arterial disease (PAD) include pain on walking (claudication), pain at rest, and loss of tissue integrity in the distal limbs; the latter may ultimately lead to amputation of a portion of the lower extremity. Surgical bypass techniques and percutaneous catheter-based interventions may be used to successfully revascularize the limbs of certain patients with PAD. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and/or healing of ischemic ulcers. No effective medical therapy is available for the treatment of such patients. The purpose of this clinical protocol is to document the safety of therapeutic angiogenesis achieved in this case by percutaneous catheter-based delivery of the gene encoding vascular endothelial growth factor (VEGF) in patients with PAD; and, as secondary objectives, investigate the bioactivity of this strategy to relieve rest pain and heal ischemic ulcers of the lower extremities. The rationale for this human protocol is based upon preclinical studies performed in a rabbit model of hindlimb ischemia. These studies are described in detail below and in the manuscripts enclosed in the Appendix to this proposal. In brief, a single intra-arterial bolus of VEGF recombinant human protein, delivered percutaneously to the ischemic limb via an intravascular catheter, resulted in angiographic, hemodynamic, physiologic, and histologic evidence of augmented collateral artery development. Subsequently, similar results were achieved using an angioplasty catheter with a hydrogel-coated balloon to deliver 400 micrograms of a plasmid containing the cDNA for VEGF to the internal iliac artery in the same animal model. Accordingly, we propose to administer arterial gene (VEGF) therapy to patients with rest pain and/or ischemic leg ulcers considered not to be candidates for conventional revascularization techniques. The dose of plasmid to be administered will be progressively escalated beginning with 500 micrograms for the first four patients, 1000 micrograms for the following six patients, 2000 micrograms for the third group of six patients, and 400 micrograms for the fourth group of six patients.

Arteries↗

Structures and chromosome locations of the human MEF2A gene and a pseudogene MEF2AP.

The MEF2 family of transcription factors control the expression of muscle-specific and mitogen-induced genes. Here we describe the isolation and structure of the human MEF2A gene. The protein coding region of MEF2A is divided by 10 introns. The 3' untranslated region (UTR) is 3.7 kb in length, and it contains a region that is highly homologous with a portion of the 3' UTR of Xenopus MEF2A. A partially processed pseudogene (MEF2AP) corresponding to MEF2A was also isolated and characterized. Human MEF2A was mapped by fluorescence in situ hybridization to chromosome 15q26, and MEF2AP was mapped to chromosome 1q24 --> q25.

Animals↗

Effects of a child abuse prevention unit in health classes in four schools.

The purpose of this study was to assess changes in parenting attitudes among high school students as an effect of a child abuse prevention unit taught in a required health class. Attitudes were measured using the Adult-Adolescent Parenting Inventory (AAPI), which was administered as a pretest-posttest. This was a primary prevention approach targeting students before they become parents. The unit consisted of an overview of child abuse, normal developmental expectations of children, anger management, and positive parenting techniques. Students from 4 schools participated in the study, and most students in the sample (N = 585) demonstrated healthy parenting attitudes. Low scores on multiple scales at pretest were recorded for 3.6% of the sample. Effect of intervention was measured using paired t tests, and a positive and statistically significant effect of intervention was noted, especially in 2 of 4 schools. Low-scoring students increased scores significantly although not up to mean pretest levels for the whole sample. Recommendations for further community health nursing research and educational initiatives are supported by these findings.

Adolescent↗

CQI applications in a community hospital.

Through the use of a data-driven system utilizing a Continuous Quality Improvement (CQI) model developed by QualPro Corporation, a community hospital has impacted both administrative and clinical areas of practice. The use of QualPro's Eight-Step Method for Quality Improvement provides ongoing data to support and change nursing practice in these settings. The CQI process promotes collaborative practice for all practioners and has led to greater provider satisfaction.

Cost Savings↗

Parameters that influence the extent of site occupancy by a candidate telomere end-binding protein.

The MF3 protein specifically recognizes telomeric and non-telomeric DNA probes that can form G.G base-paired structures (Gualberto, A., Patrick, R. M., and Walsh, K. (1992) Genes & Dev. 6, 815-824). Here we further characterize the nucleic acid recognition properties of MF3 and present a mathematical analysis that evaluates the potential extent of telomere site occupancy by this factor. The substitution of dI at dG positions in telomeric DNA probes revealed that a single dG at any position within the internal repeat was sufficient for high affinity binding to MF3. The RNA analogs of high affinity DNA sites were not bound specifically by MF3, but the substitution of dU for dT in a DNA probe had little or no effect on binding. These data demonstrate that ribose ring structure is a critical feature of nucleoprotein complex formation, and this ribose specificity may enable MF3 to occupy sites of unusual DNA structure while minimizing interactions with cellular RNAs. Collectively, the nucleic acid binding properties of MF3 suggest that it may occupy a significant fraction of sites at telomere ends or other G-rich regions of altered DNA structure in vivo.

Amines↗

Aneurysmal bone cyst in a Holstein bull.

A 3-year-old Holstein bull was examined because of a mass involving the cranial portion of the right hemimandible and the oral cavity. The mass had been observed 2 weeks earlier. The bull had lost weight throughout the 45 days before admission, and was anorectic at the time of admission. An aneurysmal bone cyst of the mandible was diagnosed.

Animals↗