PubMed Health⌕ Search

Biomedical subjects

K Snyder

Publications and source records attributed to K Snyder.

At least 19 recordsLinked to original sources
PubMed2005

The Biomolecular Interaction Network Database and related tools 2005 update.

The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machine-readable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues.

Animals↗
PubMed2001

The influence of age on the response of major depression to electroconvulsive therapy: a C.O.R.E. Report.

As part of a C.O.R.E., multi-site longitudinal study comparing continuation electroconvulsive therapy (ECT) vs. continuation pharmacotherapy, the authors determined the response of 253 patients with major depression to acute-phase, bilateral ECT by use of the 24-item Hamilton Rating Scale for Depression. Remission rates for three age-groups, > or =65 years; 46-64 years; and < or =45 years, were 90 percent, 89.8 percent, and 70 percent, respectively. Age, as a continuous variable, positively influenced response to treatment. Bilateral, dose-titrated ECT is a highly effective acute treatment for major depression, and older age confers a greater likelihood of achieving remission.

Age Factors↗
PubMed2000

An alternative, human SRC promoter and its regulation by hepatic nuclear factor-1alpha.

The SRC gene encodes the proto-oncogene pp60(c-)(src), a tyrosine kinase implicated in numerous signal transduction pathways. In addition, the SRC gene is differentially expressed, developmentally regulated, and frequently overexpressed in human neoplasia. However, the mechanisms regulating its expression have not been completely explored. Here we describe the isolation of a new distal SRC promoter and associated exon, designated 1alpha, which we mapped to a position 1.0 kilobase upstream of the previously described SRC1A housekeeping promoter. Differential use of these promoters and their associated exons coupled with subsequent splicing to a common downstream exon results in c-Src transcripts with different 5' ends but identical coding regions. Promoter analysis following transient transfections into HepG2 cells mapped the minimal 1alpha promoter to a region 145 bp upstream of the major transcription start site. This region contained a consensus binding site for hepatic nuclear factor-1 (HNF-1), a liver-enriched transcription factor implicated in the regulation of a number of genes in liver, kidney, stomach, intestine, and pancreas. Subsequent mobility shift assays confirmed that HNF-1alpha isoform was the predominant factor interacting with this region of the promoter. Mutation of the HNF-1 site resulted in a dramatic reduction in SRC promoter activity. Cotransfection studies demonstrated the promoter could be strongly transactivated by the HNF-1alpha isoform but not by the related HNF-1beta factor. Consistent with these results, we demonstrated that transcripts originating from the SRC1alpha promoter display a tissue restricted pattern of expression with highest levels present in stomach, kidney, and pancreas. These results indicate that SRC transcriptional regulation is much more complex than previously realized and implicates HNF-1 in both the tissue-specific regulation of the SRC gene in normal tissues and the overexpression of c-Src in certain human cancers.

Base Sequence↗
PubMed1999

Matrix metalloproteinase inhibitor prevents acute lung injury after cardiopulmonary bypass.

BACKGROUND: Acute lung injury (ALI) after cardiopulmonary bypass (CPB) results from sequential priming and activation of neutrophils. Activated neutrophils release neutral serine, elastase, and matrix metalloproteinases (MMPs) and oxygen radical species, which damage alveolar-capillary basement membranes and the extracellular matrix, resulting in an ALI clinically defined as adult respiratory distress syndrome (ARDS). We hypothesized that treatment with a potent MMP and elastase inhibitor, a chemically modified tetracycline (CMT-3), would prevent ALI in our sequential insult model of ALI after CPB. METHODS AND RESULTS: Anesthetized Yorkshire pigs were randomized to 1 of 5 groups: control (n=3); CPB (n=5), femoral-femoral hypothermic bypass for 1 hour; LPS (n=7), sham bypass followed by infusion of low-dose Escherichia coli lipopolysaccharide (LPS; 1 microgram/kg); CPB+LPS (n=6), both insults; and CPB+LPS+CMT-3 (n=5), both insults plus intravenous CMT-3 dosed to obtain a 25-micromol/L blood concentration. CPB+LPS caused severe lung injury, as demonstrated by a significant fall in PaO(2) and an increase in intrapulmonary shunt compared with all groups (P<0.05). These changes were associated with significant pulmonary infiltration of neutrophils and an increase in elastase and MMP-9 activity. CONCLUSIONS: All pathological changes typical of ALI after CPB were prevented by CMT-3. Prevention of lung dysfunction followed an attenuation of both elastase and MMP-2 activity. This study suggests that strategies to combat ARDS should target terminal neutrophil effectors.

Acute Disease↗
PubMed1999

Multiple sequential insults cause post-pump syndrome.

BACKGROUND: We hypothesize that post-pump syndrome (PPS) following cardiopulmonary bypass (CPB) can be caused by multiple minor insults and that the mechanism of PPS is a priming and subsequent activation of polymorphonuclear (PMN) leukocytes. In this study extensive pathophysiologic and morphometric assessment was undertaken in a porcine model of sequential insult PPS. METHODS: Pigs were anesthetized, placed on a ventilator, instrumented for measurements of hemodynamic function, and separated into five groups: (1) Control (n = 4)--surgery only, (2) CPB (n = 4)--placed on femoral-femoral hypothermic (28 degrees C) bypass for 1 h, (3) LPS (n = 6)--underwent sham CPB followed by infusion of low dose endotoxin [E. coli lipopolysaccharide (LPS-1 microg/kg)], (4) Heparin + protamine + LPS (HP + LPS, n = 4)--were heparinized without CPB for 1 h, following which protamine and LPS were infused and (5) CPB + LPS (n = 8)--subjected to both CPB and LPS. RESULTS: Only CPB + LPS resulted in acute respiratory distress typical of PPS as indicated by a significant decrease in PaO2 and increase in intrapulmonary shunt fraction (p<0.05). CPB + LPS significantly increased tissue density and the number of sequestered monocytes and PMNs (p<0.05) above all other groups. Alveolar macrophages (AM) increased equally in all groups receiving LPS. CONCLUSIONS: CPB primes the inflammatory system causing pulmonary PMN sequestration without lung injury. Exposure to an otherwise benign dose of endotoxin results in activation of the sequestered PMNs causing PPS. This study confirms that PPS can be caused by multiple minor insults.

Animals↗
PubMed1998

Animal behavior models. Increased sensitivity to stressors and other environmental experiences after prenatal cocaine exposure.

Neural compensations occurring after prenatal cocaine exposure may often permit some functional recovery, although the cost of this reorganization may be a decrease in adaptability. As we have seen in our rodent model of prenatal cocaine exposure, latent deficits may become unmasked when offspring are exposed to cognitive and environmental demands and stressors. In adolescence and adulthood, offspring exposed gestationally to cocaine exhibit characteristic decreases in stress-induced immobility along with increases in aggression under the demands of social competition. Recently, we observed that cocaine-exposed offspring are also unusually sensitive to the long-term effects of early manipulation (noninvasive heart rate testing at 16 days of age). When tested in adulthood, cocaine-exposed offspring not receiving this early experience exhibited less immobility when tested in the presence of intermittent footshock or when subsequently examined in an open field as well as more locomotion in the open field than control offspring, findings reminiscent of previous work. By contrast, these effects were normalized (shock-induced immobility) or reversed (open field immobility and locomotion) in cocaine-exposed animals given the early experience. This marked susceptibility to the effects of early manipulation was less evident in control offspring and even in a group of stunted nutritional controls. Thus, cocaine-exposed offspring may exhibit increased sensitivity not only to environmental demands and stressors, but also to the potential moderating or beneficial effects of early experiences.

Aging↗
PubMed1998

Electronic medical records as tools for quality improvement in ambulatory practice: theory and a case study.

Information management is critical in today's health care environment. Traditional paper-based medical records are inadequate information management tools. Electronic medical records (EMRs) overcome many problems with paper records and are ideally suited to help physicians increase productivity and improve the quality of care they provide. The Department of Family Medicine at the Medical University of South Carolina uses the Practice Partner Patient Record EMR system. Department members have developed a quality improvement model based on this EMR system. The model has been used to improve care for acute bronchitis, diabetes mellitus, tobacco abuse, asthma, and postmenopausal osteoporosis.

Academic Medical Centers↗
PubMed1997

Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior.

gamma-Aminobutyric acid type A receptors (GABA(A)-Rs) mediate the bulk of rapid inhibitory synaptic transmission in the central nervous system. The beta3 subunit is an essential component of the GABA(A)-R in many brain regions, especially during development, and is implicated in several pathophysiologic processes. We examined mice harboring a beta3 gene inactivated by gene targeting. GABA(A)-R density is approximately halved in brain of beta3-deficient mice, and GABA(A)-R function is severely impaired. Most beta3-deficient mice die as neonates; some neonatal mortality, but not all, is accompanied by cleft palate. beta3-deficient mice that survive are runted until weaning but achieve normal body size by adulthood, although with reduced life span. These mice are fertile but mothers fail to nurture offspring. Brain morphology is grossly normal, but a number of behaviors are abnormal, consistent with the widespread location of the beta3 subunit. The mice are very hyperactive and hyperresponsive to human contact and other sensory stimuli, and often run continuously in tight circles. When held by the tail, they hold all paws in like a ball, which is frequently a sign of neurological impairment. They have difficulty swimming, walking on grids, and fall off platforms and rotarods, although they do not have a jerky gait. beta3-deficient mice display frequent myoclonus and occasional epileptic seizures, documented by electroencephalographic recording. Hyperactivity, lack of coordination, and seizures are consistent with reduced presynaptic inhibition in spinal cord and impaired inhibition in higher cortical centers and/or pleiotropic developmental defects.

Angelman Syndrome↗
PubMed1997

Gene knockout of the alpha6 subunit of the gamma-aminobutyric acid type A receptor: lack of effect on responses to ethanol, pentobarbital, and general anesthetics.

The alpha6 subunit of the gamma-aminobutyric acid type A receptor (GABA(A)-R) has been implicated in mediating the intoxicating effects of ethanol and the motor ataxic effects of general anesthetics. To test this hypothesis, we used gene targeting in embryonic stem cells to create mice lacking a functional alpha6 gene. Homozygous mice are viable and fertile and have grossly normal cerebellar cytoarchitecture. Northern blot and reverse transcriptase-polymerase chain reaction analyses demonstrated that the targeting event disrupted production of functional alpha6 mRNA. Autoradiography of histological sections of adult brains demonstrated that diazepam-insensitive binding of [3H]Ro15-4513 to the cerebellar granule cell layer of wild-type mice was completely absent in homozygous mice. Cerebellar GABA(A)-R density was unchanged in the mutant mice; however, the apparent affinity for muscimol was markedly reduced. Sleep time response to injection of ethanol after pretreatment with vehicle or Ro15-4513 did not differ between genotypes. Sleep time response to injection of pentobarbital and loss of righting reflex and response to tail clamp stimulus in mice anesthetized with volatile anesthetics also did not differ between genotypes. Thus, the alpha6 subunit of the GABA(A)-R is not required for normal development, viability, and fertility and does not seem to be a critical or unique component of the neuronal pathway mediating the hypnotic effect of ethanol and its antagonism by Ro15-4513 in mice. Similarly, the alpha6 subunit does not seem to be involved in the behavioral responses to general anesthetics or pentobarbital.

Anesthetics, Inhalation↗
PubMed1995

Relative size and evolution of the germline repertoire of T-cell receptor beta-chain gene segments in nonhuman primates.

The mammalian T-cell receptor (TCR) gene complexes exist as multiple tandemly arrayed gene segments that have apparently arisen by gene duplication mechanisms. A study of the number of TCR germline gene segments in several primate species might provide insight into the relative rate and patterns of gene duplication and deletion within these gene complexes. DNA probes from the TCR beta-chain variable (TCRBV) region gene segment subfamilies 1 through 25 and the constant region gene segment were sequentially hybridized under low stringency to Southern blots containing genomic DNA of human, gorilla, orangutan, and pig-tailed macaque. The number of gene members in each subfamily was estimated from the number of hybridizing DNA fragments. The results show apparent examples of both TCRB V gene duplication and deletion since speciation of the Hominoids from Cercopithecoid (Old World) primates. For one putative duplication/deletion event involving six TCRBV gene segments, derivation and comparison of germline DNA sequence from macaque and human as well as Southern blot analysis of additional primates demonstrated that this event was a duplication that occurred after the divergence of the family Pongidae (Greater Apes) from Hylobatidae (Lesser Apes). Southern blot analysis of multiple pig-tailed macaques and their offspring suggests a degree of DNA sequence variability in these gene segments similar to that observed in humans. An appreciation of the size and variability of each TCRBV subfamily will be useful when considering the DNA primers and probes necessary to measure the relative usage of these TCRBV genes as part of the immune response in these nonhuman primates.

Animals↗
PubMed1994

Effects of exogenous interleukin-10 in a murine model of graft-versus-host disease to minor histocompatibility antigens.

IL-10 is a regulatory cytokine of both T cells and monocytes. We have investigated the ability of IL-10 to regulate responses to alloantigens in vitro and in vivo. Addition of IL-10 to mixed lymphocyte cultures profoundly decreased the proliferation and IL-2 production by donor B10.BR cells stimulated with CBA cells expressing minor histocompatibility antigens. Administration of IL-10 for a period of 2 weeks after bone marrow transplantation decreased the expansion of CD4+ and CD8+ donor T cells. In addition, splenocytes from BMT mice treated with IL-10 secreted less IFN-gamma after stimulation with Con A in vitro. The suppression of the mitogen-driven proliferative response of lymphocytes from the IL-10-treated group could also be reversed with significantly less anti-IFN-gamma antibody than for saline-treated controls. However, treatment with IL-10 was not sufficient to alter significantly the clinical course of graft-versus-host disease in CBA recipient mice as assessed by survival, weight loss, and splenomegaly. The results suggest that exogenous IL-10 suppresses the afferent Th1 response in a graft-versus-host reaction but does not significantly diminish the effector stage of graft-versus-host disease.

Animals↗
PubMed1991

Tom, Huck, and Oliver Stone as advocates in Kohlberg's just community: theory-based strategies for moral education.

Kohlberg's studies of moral reasoning provide a good theoretical framework for describing the developmental process that may serve as the basis for programs of moral education for adolescents. Kohlberg viewed moral education, particularly during adolescence, as the stimulation of the natural developmental process which leads to mature moral reasoning. Building on Kohlberg's work, specifically his concept of the just community approach where the teacher and more advanced peers serve as advocates of mature moral reasoning, this article presents the educator with a theoretical rationale for implementing procedures that can foster moral development. A case is made for using contemporary films and literature as mechanisms for stimulating moral development among adolescents.

Adolescent↗
PubMed1990

Amplified expression of three jun family members inhibits erythroleukemia differentiation.

Several different proto-oncogenes have been shown to influence cellular differentiation. One of the most widely studied model systems has been the Friend murine erythroleukemia cell (F-MELC) line, which can be induced to undergo erythroid differentiation by a variety of chemical agents. Constitutive overexpression of either the c-myc or c-myb proto-oncogenes has been previously shown to inhibit F-MELC differentiation, whereas c-myc antisense sequences accelerate the process. To investigate the potential involvement of other proto-oncogenes and immediate early response genes in F-MELC differentiation, we studied the expression of the three known members of the jun family as well as another gene, egr-1, which, like the jun family members, is expressed as an immediate early response gene in growth factor-stimulated quiescent cells. All four genes were expressed in F-MELC, although the levels of expression and modes of regulation differed. Transfection with amplifiable c-jun, junB, or junD expression plasmids inhibited differentiation, whereas transfection with an egr-1 expression plasmid was without effect. These results indicate that jun family members play a role in mediating F-MELC differentiation. The known inhibitory effect of phorbol ester tumor promoters on F-MELC differentiation may be the result of their known stimulation of jun expression.

Cell Line↗
PubMed1990

Coexpression of the human papillomavirus type 16 E4 and L1 open reading frames in early cervical neoplasia.

Although the E4 open reading frame (ORF) of human papillomaviruses (HPV) encodes an abundant protein in cutaneous warts, the location and extent of HPV E4 expression in genital precancers, specifically those associated with HPV-16, has not been described. Expression plasmids (pATH) containing segments of the HPV-16 E4 (3401-3620) and L1 (6151-6792) open reading frames (ORFs) were induced and expressed in bacteria and the resulting fusion proteins were used to elicit antisera in rabbits. Antisera reacting to the E4 and L1 components of the fusion proteins were used to screen biopsies from 150 cervical precancers (cervical intraepithelial neoplasia) and condylomata. Six biopsies exhibiting specific immunostaining with the anti-E4 sera. Staining was cytoplasmic, and occurred virtually always in foci containing immunostaining for L1 proteins. Moreover, analysis of these 6 cases and 22 others for HPV-16 RNA by RNA-RNA in situ hybridization demonstrated a similar correlation between E4 immunostaining and the presence of abundant transcripts specific to HPV-16. These data are consistent with the hypothesis that expression of the HPV-16 E4 ORF is dependent upon viral replication and epithelial differentiation, similar to L1 expression, and that the E4 epitopes identified by the rabbit antisera may be unique to HPV-16 relative to other common cervical papillomaviruses.

Condylomata Acuminata↗
PubMed1990

Maternal transmission of type D simian retrovirus (SRV-2) in pigtailed macaques.

Pregnant macaques were used as a natural model for maternal-infant transmission of SRV-2 retrovirus. Fifty-one pregnant females were placed into one of four virus/antibody groups. Nonviremic mothers produced 100% virus-negative offspring at birth. In contrast, viremic mothers produced offspring which were 17% virus-negative and 83% virus-positive at birth. SRV-2 infection occurred principally in utero by the transplacental route. Infants born to viremic mothers exhibited low birth weight, prematurity, high perinatal death, and increased incidence of SAIDS.

Animals↗