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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 181 records · Page 10Linked to original sources
PubMed2001

Widowhood and illness: a comparison of social network characteristics in France, Germany, Japan, and the United States.

This study examined social network characteristics of adults aged 70 to 90 years in relation to widowhood and illness in France, Germany, Japan, and the United States. Participants were drawn from representative samples from each of the 4 countries (total N = 1,331). Resource deficit profiles based on whether respondents were widowed, ill, both, or neither were directly related to social network characteristics for German and Japanese adults, were differentially related by gender and age for French adults, and were not related to social networks of Americans. Country, gender, and age differences in total network size, proportion of close network members, and frequency of contact with network members are reported. Similarities and differences found in the associations between normative late-life deficits and social network characteristics in the 4 countries point to the importance of investigating sociocultural factors that mediate the impact of resource loss and afford life quality in very old age.

Aged↗
PubMed2001

Tax-advantaged investing: a wise choice.

Your investment strategy should be just that--a plan to make the most of your assets. Considering the tax advantages and disadvantages help you stretch your investments and take full advantage of stocks, mutual funds, and other investments.

Financial Management↗
PubMed2001

Education planning for today.

Parents have several options when it comes to saving for a child's college education. The choices vary as to how early you begin; mutual funds, education IRAs, and prepaid tuition plans are among the choices when your children are young. If you don't start saving until your child is in high school, your choices can include loans and financial aid.

Education↗
PubMed2000

Point-of-care versus laboratory measurement of the International Normalized Ratio.

The Notes section welcomes the following types of contributions: (1) practical innovations or solutions to everyday practice problems, (2) substantial updates or elaborations on work previously published by the same authors, (3) important confirmations of research findings previously published by others, and (4) short research reports, including practice surveys, of modest scope or interest. Notes should be submitted with AJHP's manuscript checklist. The text should be concise, and the number of references, tables, and figures should be limited.

Adult↗
PubMed2000

Transvenous biventricular defibrillation.

The recent success of biventricular pacing with transvenously implantable left ventricular leads suggests that left ventricular leads may be useful for other modes of therapy. Animal studies showed small leads inserted into a left ventricular vein dramatically reduced defibrillation strength requirements. This article describes a human investigation of the feasibility of biventricular defibrillation. Fifty-one patients undergoing implantable cardioverter defibrillator (ICD) implantation were enrolled. After insertion of a standard ICD lead, a prototype over-the-wire left ventricular defibrillation lead was inserted through the coronary sinus and into a vein on the left ventricle. Lead insertion was guided by retrograde venography. The left ventricular lead's location was randomized to the anterior or posterior vein. Randomized, paired defibrillation threshold (DFT) testing was performed to compare a standard ICD shock configuration (Control: right ventricle- --> superior vena cava+ + CAN+) to 1 of 3 biventricular shock configurations. In the anterior vein, the left ventricular lead was tested with either a single biphasic shock from right ventricle + left ventricle- --> superior vena cava+ + CAN+ or a dual biphasic shock. In the posterior vein, the left ventricular lead was tested with a dual biphasic shock. Dual shocks consisted of a 40% tilt biphasic shock from right ventricle- --> superior vena cava+ + CAN+ followed by another 40% tilt biphasic shock from left ventricle- --> superior vena cava+ + CAN+, delivered from a single 225 microF capacitance. Left ventricular lead positioning was successful in 41 of 46 patients (89%). Mean left ventricular lead insertion time was 17 +/- 17 minutes and 13 +/- 15 minutes for anterior and posterior locations, respectively. Mean DFTs were not statistically lower for the left ventricular shock configurations, but retrospective analysis showed a well-defined region of the posterolateral left ventricle where consistent DFT reduction was achieved with dual shocks (14.0 +/- 2.7 J vs 7.8 +/- 0.9 J; n = 5; p = 0.04). There were no adverse events requiring intervention due to the use of the left ventricular lead. Biventricular defibrillation is feasible and safe under the conditions used in this study. Additional studies are needed to verify whether dual shocks with posterolateral left ventricular lead positions consistently reduce DFTs.

Aged↗
PubMed2000

Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains.

This study concerns chimeric restriction enzymes that are hybrids between a zinc finger DNA-binding domain and the non-specific DNA-cleavage domain from the natural restriction enzyme FOK:I. Because of the flexibility of DNA recognition by zinc fingers, these enzymes are potential tools for cleaving DNA at arbitrarily selected sequences. Efficient double-strand cleavage by the chimeric nucleases requires two binding sites in close proximity. When cuts were mapped on the DNA strands, it was found that they occur in pairs separated by approximately 4 bp with a 5' overhang, as for native FOK:I. Furthermore, amino acid changes in the dimer interface of the cleavage domain abolished activity. These results reflect a requirement for dimerization of the cleavage domain. The dependence of cleavage efficiency on the distance between two inverted binding sites was determined and both upper and lower limits were defined. Two different zinc finger combinations binding to non-identical sites also supported specific cleavage. Molecular modeling was employed to gain insight into the precise location of the cut sites. These results define requirements for effective targets of chimeric nucleases and will guide the design of novel specificities for directed DNA cleavage in vitro and in vivo.

Amino Acid Sequence↗
PubMed2000

Primary care groups. Serving from the shadows.

A study of appointments to the boards of 59 PCGs covered by the 13 health authorities in the West Midlands found concerns about fairness, openness and transparency. There was concern about the lack of a competency framework for GP members. Health authorities questioned whether the lay members of boards were representative of the local population. Some health authorities provided no induction training for boards.

Community Participation↗
PubMed2000

Redox state is a central modulator of the balance between self-renewal and differentiation in a dividing glial precursor cell.

We have discovered that intracellular redox state appears to be a necessary and sufficient modulator of the balance between self-renewal and differentiation in dividing oligodendrocyte-type-2 astrocyte progenitor cells. The intracellular redox state of freshly isolated progenitors allows prospective isolation of cells with different self-renewal characteristics. Redox state is itself modulated by cell-extrinsic signaling molecules that alter the balance between self-renewal and differentiation: growth factors that promote self-renewal cause progenitors to become more reduced, while signaling molecules that promote differentiation cause progenitors to become more oxidized. Moreover, pharmacological antagonists of the redox effects of these cell-extrinsic signaling molecules antagonize their effects on self-renewal and differentiation, indicating that cell-extrinsic signaling molecules that modulate this balance converge on redox modulation as a critical component of their effector mechanism.

Acetylcysteine↗
PubMed2000

Structure-based design of an osteoclast-selective, nonpeptide src homology 2 inhibitor with in vivo antiresorptive activity.

Targeted disruption of the pp60(src) (Src) gene has implicated this tyrosine kinase in osteoclast-mediated bone resorption and as a therapeutic target for the treatment of osteoporosis and other bone-related diseases. Herein we describe the discovery of a nonpeptide inhibitor (AP22408) of Src that demonstrates in vivo antiresorptive activity. Based on a cocrystal structure of the noncatalytic Src homology 2 (SH2) domain of Src complexed with citrate [in the phosphotyrosine (pTyr) binding pocket], we designed 3',4'-diphosphonophenylalanine (Dpp) as a pTyr mimic. In addition to its design to bind Src SH2, the Dpp moiety exhibits bone-targeting properties that confer osteoclast selectivity, hence minimizing possible undesired effects on other cells that have Src-dependent activities. The chemical structure AP22408 also illustrates a bicyclic template to replace the post-pTyr sequence of cognate Src SH2 phosphopeptides such as Ac-pTyr-Glu-Glu-Ile (1). An x-ray structure of AP22408 complexed with Lck (S164C) SH2 confirmed molecular interactions of both the Dpp and bicyclic template of AP22408 as predicted from molecular modeling. Relative to the cognate phosphopeptide, AP22408 exhibits significantly increased Src SH2 binding affinity (IC(50) = 0.30 microM for AP22408 and 5.5 microM for 1). Furthermore, AP22408 inhibits rabbit osteoclast-mediated resorption of dentine in a cellular assay, exhibits bone-targeting properties based on a hydroxyapatite adsorption assay, and demonstrates in vivo antiresorptive activity in a parathyroid hormone-induced rat model.

Adsorption↗
PubMed2000

Improved mucosal protection against Venezuelan equine encephalitis virus is induced by the molecularly defined, live-attenuated V3526 vaccine candidate.

The genetically engineered, live-attenuated Venezuelan equine encephalitis (VEE) virus vaccine candidate, V3526, was evaluated as a replacement for the TC-83 virus vaccine. Protection from lethal subcutaneous or aerosol challenge was evaluated in vaccinated mice clinically and immunohistochemically. Subcutaneous administration of V3526 induced systemic and mucosal protection more efficiently than did the TC-83 vaccine. The bronchial IgA responses induced in mice by subcutaneous administration of vaccines significantly corresponded to the ability to survive aerosol challenge with virulent virus. Furthermore, V3526 delivered by aerosol induced more complete mucosal protection than either vaccine administered subcutaneously. The ability of V3526 to induce protection in mice warrants its consideration for further testing as a potential vaccine candidate for human use.

Aerosols↗
PubMed2000

Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells.

The ligand for the receptor tyrosine kinase fms-like tyrosine kinase 3 (flt3), also referred to as fetal liver kinase-2 (flk-2), has an important role in hematopoiesis. The flt3 ligand (flt3L) is a growth factor for hematopoietic progenitors and induces hematopoietic progenitor and stem cell mobilization in vivo. In addition, when mice are treated with flt3L immature B cells, natural killer (NK) cells and dendritic cells (DC) are expanded in vivo. To further elucidate the role of flt3L in hematopoiesis, mice lacking flt3L (flt3L-/-) were generated by targeted gene disruption. Leukocyte cellularity was reduced in the bone marrow, peripheral blood, lymph nodes (LN), and spleen. Thymic cellularity, blood hematocrit, and platelet numbers were not affected. Significantly reduced numbers of myeloid and B-lymphoid progenitors were noted in the BM of flt3L-/- mice. In addition a marked deficiency of NK cells in the spleen was noted. DC numbers were also reduced in the spleen, LN, and thymus. Both myeloid-related (CD11c(++) CD8alpha(-)) and lymphoid-related (CD11c(++) CD8alpha(+)) DC numbers were affected. We conclude that flt3L has an important role in the expansion of early hematopoietic progenitors and in the generation of mature peripheral leukocytes.

Animals↗
PubMed2000

Increased IGF-II protein affects p57kip2 expression in vivo and in vitro: implications for Beckwith-Wiedemann syndrome.

In both human and mouse, the Igf2 gene, localized on chromosomes 11 and 7, respectively, is expressed from the paternally inherited chromosome in the majority of tissues. Insulin-like growth factor-II (IGF-II) plays an important role in embryonic growth, and aberrant IGF2 expression has been documented in several human pathologies, such as Beckwith-Wiedemann syndrome (BWS), and a wide variety of tumors. Human and mouse genetic data strongly implicate another gene, CDKN1C (p57(kip2)), located in the same imprinted gene cluster on human chromosome II, in BWS. p57(KIP2) is a cyclin-dependent kinase inhibitor and is required for normal mouse embryonic development. Mutations in CDKN1C (p57(kip2)) have been identified in a small proportion of patients with BWS, and removal of the gene from mice by targeted mutagenesis produces a phenotype with elements in common with this overgrowth syndrome. Patients with BWS with biallelic expression of IGF2 or with a CDKN1C (p57(kip2)) mutation, as well as overlapping phenotypes observed in two types of mutant mice, the p57(kip2) knockout and IGF-II-overexpressing mice, strongly suggest that the genes may act in a common pathway of growth control in situations where Igf2 expression is abnormal. Herein, we show that p57(kip2) expression is reduced on IGF-II treatment of primary embryo fibroblasts in a dose-dependent manner. In addition, p57(kip2) expression is down-regulated in mice with high serum levels of IGF-II. These data suggest that the effects of increased IGF-II in BWS may, in part, be mediated through a decrease in p57(kip2) gene expression.

3T3 Cells↗