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Biomedical subjects

K Johnson

Publications and source records attributed to K Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1999

Companion animal issues and the physician.

BACKGROUND: The companion animal population in the United States is both large in numbers and diverse in composition. Nearly 60% of households have one or more animals. Associated with this large and diverse group of animals are considerable risks for injuries and transmission of infections to humans. METHODS: Through a review of the relevant literature and our collective professional experience in public health and veterinary medicine, we framed issues regarding companion animals and human health and safety. RESULTS: We placed the identified issues in general contexts that could be applied to varying circumstances. CONCLUSIONS: Physicians, veterinarians, public health officials, and others need to work together to ensure that animal ownership is as risk free for people as possible.

Animals↗
PubMed1999

Formants of children, women, and men: the effects of vocal intensity variation.

The purpose of this study was to investigate the formant frequencies and amplitudes of a wide age range of children and one group of adults at three sound pressure levels (SPLs). Subjects were ten females and ten males in the following age groups (in years): 4, 6, 8, 10, 12, 14, 16, 18, and adults. A sustained /a/ was produced three times by each subject. Formant frequencies were obtained using linear predictive coding analysis. Formant amplitudes were measured from the highest amplitude harmonic in the area of each formant. In addition to following established trends previously published in other studies, it was hypothesized that the first formant frequency would increase with increasing intensity, that females would have higher formant frequencies than same aged males, and that women and children would have reduced formant amplitudes as compared to men. It was found that first formant frequency increased with intensity and changed as a function of age and sex. Second and third formant frequencies changed with age and sex. Formant amplitudes followed the trends set by the SPL differences and did not change as a function of age and sex. Results are discussed in terms of anatomic differences and SPL.

Adolescent↗
PubMed1999

Characterization of novel antimicrobial peptoids.

Peptoids differ from peptides in that peptoids are composed of N-substituted rather than alpha-carbon-substituted glycine units. In this paper we report the in vitro and in vivo antibacterial activities of several antibacterial peptoids discovered by screening combinatorial chemistry libraries for bacterial growth inhibition. In vitro, the peptoid CHIR29498 and some of its analogues were active in the range of 3 to 12 microg/ml against a panel of gram-positive and gram-negative bacteria which included isolates which were resistant to known antibiotics. Peptoid antimicrobial activity against Staphylococcus aureus was rapid, bactericidal, and independent of protein synthesis. beta-Galactosidase and propidium iodide leakage assays indicated that the membrane is the most likely target of activity. Positional isomers of an active peptoid were also active, consistent with a mode of action, such as membrane disruption, that does not require a specific fit between the molecule and its target. In vivo, CHIR29498 protected S. aureus-infected mice in a simple infection model.

Animals↗
PubMed1999

Matrix vesicle plasma cell membrane glycoprotein-1 regulates mineralization by murine osteoblastic MC3T3 cells.

A naturally occurring nonsense truncation mutation of the inorganic pyrophosphate (PPi)-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) PC-1 is associated with spinal and periarticular ligament hyperostosis and cartilage calcification in "tiptoe walking" (ttw) mice. Thus, we tested the hypothesis that PC-1 acts directly in the extracellular matrix to restrain mineralization. Cultured osteoblastic MC3T3 cells expressed PC-1 mRNA and produced hydroxyapatite deposits at 12-14 days. NTPPPH activity increased steadily over 14 days. Transforming growth factor-beta and 1,25-dihydroxyvitamin D3 increased PC-1 and NTPPPH in matrix vesicles (MVs). Because PC-1/NTPPPH was regulated in mineralizing MC3T3 cells, we stably transfected or infected cells with recombinant adenovirus, in order to express 2- to 6-fold more PC-1. PC-1/NTPPPH and PPi content increased severalfold in MVs derived from cells transfected with PC-1. Furthermore, MC3T3 cells transfected with PC-1 deposited approximately 80-90% less hydroxyapatite (by weight) than cells transfected with empty plasmid or enzymatically inactive PC-1. ATP-dependent 45Ca precipitation by MVs from cells overexpressing active PC-1 was comparably diminished. Thus, regulation of PC-1 controls the PPi content and function of osteoblast-derived MVs and matrix hydroxyapatite deposition. PC-1 may provide a novel therapeutic target in certain disorders of bone mineralization.

Adenoviridae↗
PubMed1999

The bits and bytes of computer/Internet addiction: a factor analytic approach.

A factor analytic approach was used to explore possible constructs underlying so-called computer/Internet addiction. A 94-item survey was developed, from which two major and two minor factors were derived. Factor 1 focused on problematic computer-related behaviors in heavy users of the Internet, whereas Factor 2 focused on the usefulness and general purpose nature of computers and the Internet. Factor 3 isolated a combination of use of the Internet for sexual gratification and shyness/introversion, and Factor 4 focused on an absence of problems related to Internet use that were coupled with a mild aversion or a disinterest in this technology. These data support the notion that some individuals have a mixture of obsessive-like characteristics related specifically to their computer/Internet use but that, not surprisingly, they also exhibit a preference for on-line, rather than in-person, interactions.

Adolescent↗
PubMed1999

Attitudes toward colon cancer gene testing: factors predicting test uptake.

OBJECTIVES: Genetic discoveries in hereditary nonpolyposis colorectal cancer (HNPCC) have made possible genetic testing to determine susceptibility to this form of colorectal cancer (CRC). This study measured the uptake of genetic testing for HNPCC among first-degree relatives of CRC patients and conducted a preliminary analysis of the predictors of test uptake. MATERIALS AND METHODS: We compared 77 test acceptors and 181 decliners on demographic, medical history, and psychological characteristics, controlling for distance from the testing center. The psychological factors studied were risk perception for CRC, frequency of cancer thoughts, and perceived ability to cope with unfavorable genetic information. RESULTS: In the final regression model, after accounting for all variables, the significant predictors of test uptake were increased risk perception, greater perceived confidence in ability to cope with unfavorable genetic information, more frequent cancer thoughts, and having had at least one colonoscopy. The association between risk perception and uptake was dependent on frequency of cancer thoughts. Among those who thought about getting CRC more often, the probability of testing increased as perceived risk increased to approximately 50% likelihood of getting CRC and then leveled off. In contrast, among those who never or rarely thought about getting CRC, risk perception was unrelated to testing decision. CONCLUSIONS: Our findings are consistent with the associations reported between psychological factors and other cancer screening behaviors.

Adaptation, Psychological↗
PubMed1999

The relationship of socio-economic status and access to minimum expected therapy among female breast cancer patients in the National Cancer Institute Black-White Cancer Survival Study.

Black women are more likely to be diagnosed with later stage breast cancer and have higher mortality rates from breast cancer than white women. To determine whether cancer treatment varies for white and black women, we analyzed data from the National Cancer Institute (NCI) Black-White Cancer Survival Study (BWCSS). Data from hospital medical records, central review of histology slides, and patient interviews on 861 breast cancer cases (in situ and invasive) were examined. Minimum expected therapy was defined for each disease stage as a basic minimum course of treatment that incorporated current practice, state-of-the-art knowledge, and recommendations advanced by NIH Consensus Conferences up to and including the one held in 1985. Patients in this study were diagnosed during 1985-1986. Using logistic regression techniques, those who received at least the minimum expected therapy were compared to those who did not. Thirty-six percent of the patients with late stage disease did not receive minimum expected therapy compared to four percent of the patients with early stage disease. Older women and women with no usual source of care were significantly less likely to receive minimum expected therapy. Overall, 21% of black women did not receive minimum expected therapy compared to 15% of white women.

Adult↗
PubMed1999

Housestaff attitudes toward computer-based clinical decision support.

OBJECTIVE: To measure housestaff attitudes towards computer-based decision support and their threshold for having CDSS messages displayed. DESIGN: 770 self-administered surveys were distributed to housestaff physicians. RESULTS: 209 surveys were returned. 63% of respondents agreed or strongly agreed that CDSS would improve quality of care, while 52% agreed or strongly agreed that it would decrease adverse drug events. Respondents were neutral regarding the impact of CDSS on productivity and on their autonomy. Sixty percent approved of a reminder to consider surgical consultation in a patient with abdominal pain, while 88% approved of alerts about hypokalemia. Respondents felt both reminders should be triggered when their PPV exceeded 67%. Attitudes toward POE correlated positively with attitudes toward CDSS (Pearson's rho 0.56; p < 0.0001). Respondents who were dissatisfied with POE had a higher threshold PPV for seeing reminders. CONCLUSION: The majority of housestaff favor the implementation of a CDSS. Housestaff with favorable POE experiences were more likely to endorse CDSS, and those with negative POE experience were more likely to oppose it. The results suggest that a carefully designed CDSS with rules constructed to exceed a threshold PPV would be accepted by housestaff.

Attitude to Computers↗
PubMed1998

Potential mechanisms for a proinflammatory vascular cytokine response to coagulation activation.

We have previously shown that an anticoagulant could attenuate inflammation in animal models of sepsis with disseminated intravascular coagulation (DIC) and that coagulation activation of human whole blood ex vivo results in a proinflammatory cytokine response. The current studies were performed to better understand mechanisms for the blood cell cytokine response and extend the investigation of such a response to endothelial cells as likely contributors to a vascular inflammatory response. Utilizing cell separation techniques, it was determined that the whole blood IL-8 response to coagulation activation or thrombin, specifically, was mediated by CD14+ monocytes. Moreover, thrombin was observed to stimulate both IL-8 and IL-6 production in cultured mononuclear cells. Analyses of the effects of coagulation activation and thrombin were extended to cultured human endothelial cells, and a similar cytokine response was observed. Thrombin catalytic activity appeared essential, since hirudin reduced thrombin-stimulated proinflammatory cytokine production in cultured monocytes and endothelial cells and prothrombin only weakly mimicked the thrombin response. The endothelial cell IL-8 and IL-6 response to thrombin could be mimicked by the thrombin receptor agonist peptide (TRAP), implicating a functional role of the classic thrombin receptor. Altogether, the results facilitate a better understanding of potential proinflammatory vascular responses to coagulation activation.

Blood Coagulation↗
PubMed1998

Mechanisms of inactivation of E-cadherin in breast cancer cell lines.

Loss of E-cadherin (CDH1) function is thought to contribute to progression in breast cancer and other solid tumors by increasing proliferation, invasion, and/or metastasis. In some cases, the restoration of CDH1 function may be an important therapeutic option. This possibility will depend on the mechanism by which CDH1 is inactivated. Here we present analyses of CDH1 expression, genetic mutation, and promoter methylation in CDH1 in 10 commonly used breast cancer cell lines. Five cell lines (BT-474, MCF-7, MDA-MB-361, MDA-MB-468, and T-47D) expressed CDH1 and were genetically normal. Five others (SK-BR-3, 600 MPE, MDA-MB-134 IV, CAMA1, and MDA-MB-435) did not express CDH1. Fluorescence in situ hybridization analyses of each of these cell lines showed evidence for the physical deletion of one allele of CDH1, and three cell lines were found to carry homozygous deletions. SK-BR-3 was deleted from exon 12 through the promoter; exon 6 was deleted in MDA-MB-134 IV cells, and 600 MPE cells carried a 21-bp deletion in the splicing acceptor site for exon 9. CAMA1 seemed to have been inactivated through promoter methylation. No explanation was found for the inactivation of CDH1 in MDA-MB-435.

Alleles↗
PubMed1998

Hypotension and inflammatory cytokine gene expression triggered by factor Xa-nitric oxide signaling.

The signaling pathway initiated by factor Xa on vascular endothelial cells was investigated. Factor Xa stimulated a 5- to 10-fold increased release of nitric oxide (NO) in a dose-dependent reaction (0.1-2.5 microG/ml) unaffected by the thrombin inhibitor hirudin but abolished by active site inhibitors, tick anticoagulant peptide, or Glu-Gly-Arg-chloromethyl ketone. In contrast, the homologous clotting protease factor IXa or another endothelial cell ligand, fibrinogen, was ineffective. A factor Xa inter-epidermal growth factor synthetic peptide L (83)FTRKL(88) (G) blocking ligand binding to effector cell protease receptor-1 inhibited NO release by factor Xa in a dose-dependent manner, whereas a control scrambled peptide KFTGRLL was ineffective. Catalytically active factor Xa induced hypotension in rats and vasorelaxation in the isolated rat mesentery, which was blocked by the NO synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) but not by D-NAME. Factor Xa/NO signaling also produced a dose-dependent endothelial cell release of interleukin 6 (range 0.55-3.1 ng/ml) in a reaction inhibited by L-NAME and by the inter-epidermal growth factor peptide Leu(83)-Leu(88) but unaffected by hirudin. Maximal induction of interleukin 6 mRNA required a brief, 30-min stimulation with factor Xa, unaffected by subsequent addition of tissue factor pathway inhibitor. These data suggest that factor Xa-induced NO release modulates endothelial cell-dependent vasorelaxation and cytokine gene expression. This pathway requiring factor Xa binding to effector cell protease receptor-1 and a secondary step of ligand-dependent proteolysis may preserve an anti-thrombotic phenotype of endothelium but also trigger acute phase responses during activation of coagulation in vivo.

Animals↗
PubMed1998

Parathyroid hormone-related proteins is abundant in osteoarthritic cartilage, and the parathyroid hormone-related protein 1-173 isoform is selectively induced by transforming growth factor beta in articular chondrocytes and suppresses generation of extracellular inorganic pyrophosphate.

OBJECTIVE: Parathyroid hormone-related protein (PTHrP) is a major, locally expressed regulator of growth cartilage chondrocyte proliferation, differentiation, synthetic function, and mineralization. Because mechanisms that limit cartilage chondrocytes from maturing and mineralizing are diminished in osteoarthritis (OA), we studied PTHrP expression by articular chondrocytes. METHODS: PTHrP was studied in normal knee cartilage samples and cultured articular chondrocytes, and in cartilage specimens from knees with advanced OA, obtained at the time of joint replacement. RESULTS: PTHrP was more abundant in OA than in normal human knee articular cartilage. Both demonstrated PTH/PTHrP receptor expression. PTHrP 1-173, one of three alternatively spliced PTHrP isoforms, was exclusively expressed and induced by transforming growth factor beta in cultured chondrocytes. Chondrocytes mainly used the GC-rich P2 alternative promoter to express PTHrP messenger RNA. Inhibition by PTHrP 1-173, but not by PTHrP 1-146 or PTHrP 1-87, of inorganic pyrophosphate (PPi) elaboration suggested selective functional properties of the 1-173 isoform. Exposure to a neutralizing antibody to PTHrP increased PPi elaboration by articular chondrocytes. CONCLUSION: Increased expression of PTHrP, including the 1-173 isoform, has the potential to contribute to the pathologic differentiated functions of chondrocytes, including mineralization, in OA.

Adult↗
PubMed1998

Effects of copper and zinc on embryos and larvae of the horseshoe crab, limulus polyphemus

We investigated the short-term and long-term effects of copper and zinc on horseshoe crab (Limulus polyphemus) embryos and first instar larvae from two estuaries in New Jersey, Delaware Bay and Sandy Hook Bay. Animals were exposed to nominal metal concentrations from 0.01 to 1,000 mg/L for 24 h, 48 h, 72 h, or continuously until the endpoint for the study (successful molting or death) was reached. Larvae showed greater tolerance of Cu and Zn than embryos. Under most treatment regimes, embryos and larvae were able to survive and molt in the presence of up to 100 mg/L Cu or Zn. Unexpectedly, horseshoe crabs from the more heavily polluted site (Sandy Hook Bay) were more susceptible to heavy metals than animals from a less polluted site (lower Delaware Bay). Horseshoe crab embryos and larvae were highly resistant to heavy metals in comparison to marine crustacea. The ability of Limulus embryos and larvae to survive in the presence of heavy metals implies the potential for these contaminants to be passed on to shorebirds and other predators.

Journal Article↗
PubMed1998

Evaluation of mebrofenin hepatoscintigraphy in neonatal-onset jaundice.

BACKGROUND: The prognosis of infants with prolonged neonatal jaundice is dependent on early diagnosis because of the need for prompt surgical management of biliary atresia. OBJECTIVE: To evaluate the usefulness of 99 mTcm-trimethylbromo-iminodiacetic acid (TBIDA, mebrofenin) in the investigation of infantile jaundice. MATERIALS AND METHODS: A retrospective study was undertaken of 58 patients with unexplained prolonged neonatal jaundice. Sixty-eight scans were reviewed. RESULTS: Mebrofenin scintigraphy confirmed the presence of a choledochal cyst in three of the four cases with that diagnosis. There were no false negative results in the nine patients with extrahepatic biliary atresia (EHBA). Three further infants had an incorrect histological diagnosis of EHBA. A gall bladder was identified by US in each case and in one of these, scintigraphy showed gut excretion. In the 16 patients with no gut excretion by 24 h, the final diagnoses were intrahepatic cholestasis (n = 7), Alagille's syndrome (n = 3), neonatal hepatitis (n = 3), alpha-1-antitrypsin deficiency (n = 2) and juvenile xanthogranuloma (n = 1). Seven infants had repeat scintigraphy after the administration of ursodeoxycholic acid (URSO). This changed five non-excretors with hepatitis into excretors. Two infants with hepatitis continued to show non-excretion after URSO, but a gallbladder was identified by US in both. CONCLUSIONS: Mebrofenin scintigraphy is accurate in confirming the presence of a choledochal cyst and in refuting the diagnosis of EHBA. While histology and scintigraphy are each 100 % sensitive for the diagnosis of EHBA, neither, individually, is accurate and the investigation of prolonged neonatal jaundice requires a multi-modality imaging strategy.

Aniline Compounds↗
PubMed1998

Further evidence for a major ancient mutation underlying myotonic dystrophy from linkage disequilibrium studies in the Japanese population.

The myotonic dystrophy (DM) mutation is an unstable (CTG)n repeat, present at a copy number of 5-37 repeats on normal chromosomes but amplified to 50-3000 copies on DM chromosomes. Previous findings in Caucasian populations of a DM founder chromosome raise a question about the molecular events involved in the expansion mutation. To investigate whether a founder chromosome for the DM mutation exists in the Japanese population, we genotyped families using polymorphic markers near the (CTG)n repeat region and constructed haplotypes. Six different haplotypes were found and DM alleles were always haplotype A. To find an origin of the (CTG)n repeat mutation and to investigate the mechanism of the expansion mutation in the Japanese population we have studied 90 Japanese DM families comprising 190 affected and 130 unaffected members. The results suggest that a few common ancestral mutations in both Caucasian and Japanese populations have originated by expansion of an ancestral n = 5 repeat to n = 19-37 copies. These data support multistep models of triplet repeat expansion that have been proposed for both DM and Friedreich's ataxia.

Adult↗