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Biomedical subjects

K Baker

Publications and source records attributed to K Baker.

At least 37 records · Page 2Linked to original sources

The effect of differing scoring methods for the Tower of London task on developmental patterns of performance.

The Tower of London (TOL) task is frequently used to assess executive functioning in both adults and children, although there remains considerable controversy over what it measures and how to score it. In this study we compare two scoring methods and find that correlations between them were high for 7-year-olds (.86), and dropped to a low of .47 for adults. These results demonstrate that the TOL necessarily has different construct validity in adults and children. Second, results of one method (based on errors only) show a developmental trend in performance from middle childhood to adulthood, while the other (based on errors and time) shows a developmental progression from ages 7 to 13, but not between 13-year-olds and young adults. Thus, scoring method influences the resulting developmental model.

Adolescent↗

HIRA, the human homologue of yeast Hir1p and Hir2p, is a novel cyclin-cdk2 substrate whose expression blocks S-phase progression.

Substrates of cyclin-cdk2 kinases contain two distinct primary sequence motifs: a cyclin-binding RXL motif and one or more phosphoacceptor sites (consensus S/TPXK/R or S/TP). To identify novel cyclin-cdk2 substrates, we searched the database for proteins containing both of these motifs. One such protein is human HIRA, the homologue of two cell cycle-regulated repressors of histone gene expression in Saccharomyces cerevisiae, Hir1p and Hir2p. Here we demonstrate that human HIRA is an in vivo substrate of a cyclin-cdk2 kinase. First, HIRA bound to and was phosphorylated by cyclin A- and E-cdk2 in vitro in an RXL-dependent manner. Second, HIRA was phosphorylated in vivo on two consensus cyclin-cdk2 phosphoacceptor sites and at least one of these, threonine 555, was phosphorylated by cyclin A-cdk2 in vitro. Third, phosphorylation of HIRA in vivo was blocked by cyclin-cdk2 inhibitor p21(cip1). Fourth, HIRA became phosphorylated on threonine 555 in S phase when cyclin-cdk2 kinases are active. Fifth, HIRA was localized preferentially to the nucleus, where active cyclin A- and E-cdk2 are located. Finally, ectopic expression of HIRA in cells caused arrest in S phase and this is consistent with the notion that it is a cyclin-cdk2 substrate that has a role in control of the cell cycle.

Amino Acid Sequence↗

The slow mo mutation reduces pacemaker current and heart rate in adult zebrafish.

Genetic studies in zebrafish have focused on embryonic mutations, but many physiological mechanisms continue to mature after embryogenesis. We report here that zebrafish homozygous for the mutation slow mo can be raised to adulthood. In the embryo, the slow mo gene is needed to regulate heart rate, and its mutation causes a reduction in pacemaker current (I(h)) and slowing of heart rate (bradycardia). The homozygous adult slow mo fish continues to manifest bradycardia, without other evident ill effects. Patch-clamp analysis of isolated adult cardiomyocytes reveals that I(h) has chamber-specific properties such that the atrial current density of I(h) is far greater than the ventricular current density of I(h). I(h) is markedly diminished in cardiomyocytes from both chambers of slow mo mutant fish. Thus I(h) continues to be a critical determinant of pacemaker rate even after adult neural and humoral influences have developed. It is clear that zebrafish may be used for genetic dissection of selected physiological mechanisms in the adult.

Animals↗

Normative data for the F(p) scale of the MMPI-2: implications for clinical and forensic assessment of malingering.

Data from several clinical samples and the Minnesota Multiphasic Personality Inventory--2 standardization group are presented to familiarize the reader with response patterns of different groups on a new validity scale designed to assist in the identification of exaggeration or fabrication of psychological disturbance. Sensitivity-specificity analyses are included along with suggestions for use of the F(p) Scale with other validity scales. Cautions about setting single cutoff scores are also discussed.

Female↗

Exercise for knee osteoarthritis.

Adverse outcomes in knee osteoarthritis include pain, loss of function, and disability. These outcomes can have devastating effects on the quality of life of those suffering from the disease. Treatments have generally targeted pain, assuming that disability would improve as a direct result of improvements in pain. However, there is evidence to suggest that determinants of pain and disability differ. In general, treatments have been more successful at decreasing pain rather than disability. Many of the factors that lead to disability can be improved with exercise. Exercise, both aerobic and strength training, have been examined as treatments for knee osteoarthritis, with considerable variability in the results. The variability between studies may be due to differences in study design, exercise protocols, and participants in the studies. Although there is variability among studies, it is notable that a majority of the studies had a positive effect on pain and or disability. The mechanism of exercise remains unclear and merits future studies to better define a concise, clear exercise protocol that may have the potential for a public health intervention.

Aged↗

Human herpesviruses in the cornea.

AIMS: To determine the sensitivity and specificity of culture, immunohistochemistry (IHC), the polymerase chain reaction (PCR), and in situ hybridisation (ISH) for detecting herpes simplex virus (HSV-1) in the cornea of patients undergoing penetrating keratoplasty. To compare the incidence of HSV-1 in the cornea with that of varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). METHODS: The corneas of 110 patients, 52 with a documented history of herpes keratitis (HSK) and 58 with non-herpetic corneal disease, were investigated using IHC, PCR, ISH, and culture. RESULTS: HSV-1 DNA and antigen were detected in 82% and 74% respectively, of corneas of patients with HSK and in 22% and 15% of corneas of patients with no history of HSK. The sensitivity of PCR and IHC was 82% and 74% with a specificity of 78% and 85%, respectively. HSV-1 DNA and antigen were found more frequently and in increased amounts in corneas of patients with a short interval between their last attack of HSK and surgery. There was a good correlation between PCR and IHC in 71%. HSV-1 was isolated by culture in 2%. Latency associated transcripts were not detected using ISH. Evidence of VZV DNA or antigen was found significantly more frequently in the corneas of patients with a history of HSK (p<0.001). No evidence of EBV or CMV was found in any cornea. CONCLUSIONS: PCR and IHC are both sensitive for the detection of HSV-1 in the cornea. A combination of PCR and IHC increases the specificity for the diagnosis of HSK to 97%. HSV-1 appears to be slowly removed from the cornea. VZV and HSV-1 may co-infect the cornea.

Carrier State↗

Instillation of allogeneic lung antigen-presenting cells deficient in expression of major histocompatibility complex class I or II antigens have differential effects on local cellular and humoral immunity and on pathology in recipient murine lungs.

Recognition of allogeneic major histocompatibility complex (MHC) molecules expressed on donor lung antigen-presenting cells (APCs) by host T lymphocytes is believed to stimulate lung allograft rejection. However, the specific roles of donor MHC molecules in the rejection response is unknown. We report a murine model in which instilling allogeneic lung APCs into recipient lungs induces pathology analogous to acute rejection, and the production of interferon (IFN)-gamma, immunoglobulin (Ig) G2a, and alloantibodies in recipient lungs. Using allogeneic lung APCs (C57BL/6, I-a(b), H-2(b)) deficient in MHC class I, II, or both for instillation into lungs of BALB/c mice (I-a(d), H-2(d)), the purpose of the current study was to determine the specific roles of donor MHC molecules in stimulating local alloimmune responses. The data show that MHC class I or II on donor APCs induced IFN-gamma and IgG2a synthesis locally, though less than that induced by wild-type cells. Both MHC class I and II were required to induce alloantibody production. Instillation of wild-type or class I- or class II-deficient APCs induced comparable pathologic lesions in recipient lungs, and more severe than that induced by MHC-deficient cells. These data show that donor MHC class I and II molecules have differential effects in the stimulation of local alloimmune responses.

Animals↗

Endoscope reprocessing: taking the mystery out of high-level disinfection.

Flexible endoscopes used in otolaryngology are often unable to withstand heat sterilization. An acceptable alternative to heat sterilization for these devices used to examine the aerodigestive tract is high-level disinfection. A review of otolaryngology (ORL) nursing clinical practice indicates that there is confusion regarding the recommended disinfectant solutions to use and the proper manner in which to use them. This article describes a method that is useful in determining the level of risk of infection posed by ORL endoscopy, a description of appropriate levels of disinfection, points to consider for achieving high-level disinfection, and appropriate personal protective measures.

Disinfection↗

Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists.

Recent studies identified a short peptide motif that serves as a docking site for cyclin/cyclin-dependent kinase (cdk) 2 complexes. Peptides containing this motif block the phosphorylation of substrates by cyclin A/cdk2 or cyclin E/cdk2. Here we report that cell membrane-permeable forms of such peptides preferentially induced transformed cells to undergo apoptosis relative to nontransformed cells. Deregulation of E2F family transcription factors is a common event during transformation and was sufficient to sensitize cells to the cyclin/cdk2 inhibitory peptides. These results suggest that deregulation of E2F and inhibition of cdk2 are synthetically lethal and provide a rationale for the development of cdk2 antagonists as antineoplastic agents.

Amino Acid Sequence↗

A spontaneous corneal change in juvenile Wistar rats.

Corneal changes were seen in a shipment of male and female Charles River Wistar (Crl:(WI)BR) albino rats aged 33 days. Seventeen weeks later, varying degrees of corneal roughness were observed ophthalmoscopically in 40 of 43 males and 26 of 29 females. Corneal lesions, described clinically as multiple punctate or particulate opacities, were most often bilateral and located paracentrally. Histologically, lesions were observed in only 21 of 40 males and in 15 of 26 females which had shown clinical changes. The lesions consisted of basophilic particulate material, which occasionally formed linear plaques, lining the basement membrane of the corneal epithelium. Ultrastructurally, irregularly distributed electron-dense deposits, occasionally assuming a concentric laminar appearance, were observed. X-ray microanalysis revealed that the granules consisted predominantly of calcium and phosphorus, with trace amounts of iron, zinc, sodium and aluminium. These mineral deposits in the corneas of Wistar rats were similar to those described in other species. Awareness of this spontaneously occurring disease in Wistar rats is of importance in relation to toxicological investigations in which the cornea may be a target organ.

Aging↗

Hyperacute cerebral enhancement: the earliest predictor of hemorrhage by MR imaging?

A test to detect very early hemorrhage in acute cerebral infarct could offer a substantial increase in the safety and success of advanced stroke therapies, particularly when the use of thrombolytic therapies is contemplated. Currently, computed tomography is the standard test for the detection of cerebral hemorrhage but is not a valid predictor of potential areas of hemorrhagic transformation. A technique to evaluate the risk of hemorrhagic transformation in infarcted cerebral tissue has been conducted with contrast-enhanced magnetic resonance imaging in various animal stroke models. Knight demonstrated Gadolinium-DTPA enhancement in the territory of occluded vessels immediately in rats after reperfusion. Gadolinium enhancement was thought to predict areas of hemorrhagic transformation. Yenari and associates demonstrated in rabbit models that contrast-enhanced T1-weighted scans can reveal regions of blood-brain barrier disruption, characterized as hemorrhagic transformation in ischemic tissue. The authors report a clinical example in which hyperacute contrast-enhanced magnetic resonance imaging was the first indication of hemorrhagic transformation within 24 hours of onset of an acute cerebral infarct.

Acute Disease↗

Angiotensin II activates Stat5 through Jak2 kinase in cardiac myocytes.

Angiotensin II (Ang II) treatment was recently shown to activate Jak2, Stat1, and Stat3 proteins in cardiac myocytes. Angiotensin-converting enzyme (ACE) inhibitors have been shown to be an effective clinical treatment following myocardial infarction, implying that inhibition of Ang II production is beneficial in this pathological condition. Some of the effects of Ang II in cardiac myocytes may be mediated by the JAK-STAT signaling pathway. The AT1 receptor was the first G-protein-coupled-receptor reported to activate the JAK-STAT pathway. Recently, however, another G-protein-coupled-receptor (i.e. serotonin) was also shown to signal through the JaK2 and STAT proteins in myoblasts. We hypothesized that Ang II treatment might also activate Stat5 transcription factors in cardiac myocytes. In this study, we provide evidence that the G-protein-coupled, Ang II type I (AT1) receptor couples to activation of Stat5 through Jak2 kinase in neonatal rat ventricular myocytes. Angiotensin II induces a 1.5- to 10-fold increase in a Stat5 transcription complex, which binds to the prolactin-inducing element (PIE). By Western analysis, Stat5 protein levels were shown to be tyrosine phosphorylated two- to three-fold over control, following. Ang II treatment of cardiac myocytes. Phosphorylation of Stat5a and Stat5b proteins was rapid and sustained (30-60 min), and Jak2 kinase co-immunoprecipitated with activated Stat5 proteins. In cardiac myocytes, Stat5 proteins co-immunoprecipitated with the AT1 receptor. Selective inhibition of Jak2 kinase with AG-490 blocked formation of prolactin-inducing factor (PIF) complexes by Ang II, suggesting that Jak2 kinase was required for the tyrosine phosphorylation of Stat5 in cardiac myocytes.

Amino Acid Sequence↗