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Biomedical subjects

R Kapur

Publications and source records attributed to R Kapur.

At least 19 recordsLinked to original sources

Releasing the therapeutic potential of the psychiatric nurse: a human relations perspective of the nurse-patient relationship.

In psychiatry mental health nurses form the largest professional discipline providing care on an everyday basis for sustained periods. Mental health nurses therefore are in a pivotal position to establish valued therapeutic alliances. In practice, however, a disproportionate amount of nursing time is taken up by administration, time spent talking to patients is minimal and when interactions do occur they remain notionally therapeutic and often are not theoretically informed. This noted paucity of therapeutic contact is antithetical to the aspirations of service users who increasingly are asking for a more skilled approach to the talking-listening that occurs in the therapeutic encounter. It is hypothesized by the present authors that an object-relations perspective of the nurse-patient relationship could release the largely untapped therapeutic potential of the psychiatric nurse by (1) bridging the gap between theory and practice and (2) providing a professional identity from within which nurses can begin to 'get to know' and understand the predicament of the patient with severe mental illness.

Humans↗

Clinicopathological significance of Borderline Nuclear Change - High Grade Dyskaryosis Not Excluded.

During a recent discussion on classification of cervical cytology, the introduction of a 'Borderline Nuclear Change - High Grade Dyskaryosis Not Excluded' (BNCH) category was proposed. BNCH cases diagnosed prospectively were retrieved from laboratory records. Questionnaires were sent to referring practitioners regarding clinicopathological outcome. Cytopathological features resulting in the BNCH classification were recorded on slide review. A total of 103 reports on conventional cervical smears diagnosed as BNCH from 1999 to 2002 were retrieved, comprising 0.096% of 107 634 smears. Of 86/103 cases with clinical follow-up, CIN2 or worse was present in 30 (35%); 15 (17%) showed a borderline/low-grade abnormality and 41 (48%) were negative. No individual cytopathological feature was predictive of high-grade disease on follow-up. The yield of high-grade abnormalities on follow-up of BNCH supports the introduction of this terminology.

Artifacts↗

Signaling by mechanical strain involves transcriptional regulation of proinflammatory genes in human periodontal ligament cells in vitro.

Intracellular signals generated by mechanical strain profoundly affect the metabolic function of osteoblast-like periodontal ligament (PDL) cells, which reside between the tooth and alveolar bone. In response to applied mechanical forces, PDL cells synthesize bone-resorptive cytokines to induce bone resorption at sites exposed to compressive forces and deposit bone at sites exposed to tensile forces in an environment primed for catabolic processes. The intracellular mechanisms that regulate this bone remodeling remain unclear. Here, in an in vitro model system, we show that tensile strain is a critical determinant of PDL-cell metabolic functions. Equibiaxial tensile strain (TENS), when applied at low magnitudes, acts as a potent antagonist of interleukin (IL)-1beta actions and suppresses transcriptional regulation of multiple proinflammatory genes. This is evidenced by the fact that TENS at low magnitude: (i) inhibits recombinant human (rh)IL-1beta-dependent induction of cyclooxygenase-2 (COX-2) mRNA expression and production of prostaglandin estradiol (PGE2); (ii) inhibits rhIL-1beta-dependent induction matrix metalloproteinase-1 (MMP-1) and MMP-3 synthesis by suppressing their mRNA expression; (iii) abrogates rhIL-1beta-induced suppression of tissue inhibitor of metalloprotease-II (TIMP-II) expression; and (iv) reverses IL-1beta-dependent suppression of osteocalcin and alkaline phosphatase synthesis. Nevertheless, these actions of TENS were observed only in the presence of IL-1beta, as TENS alone failed to affect any of the aforementioned responses. The present findings are the first to show that intracellular signals generated by low-magnitude mechanical strain interfere with one or more critical step(s) in the signal transduction cascade of rhIL-1beta upstream of mRNA expression, while concurrently promoting the expression of osteogenic proteins in PDL cells.

Dental Stress Analysis↗

Perception of orthodontic treatment need: opinion comparisons of orthodontists, pediatric dentists, and general practitioners.

AIM: To determine the relationship between treatment need assessment scores of orthodontists, general practitioners, and pediatric dentists. STUDY DESIGN: Observational. SAMPLE: Ten general dental practitioners, 18 orthodontists and 15 pediatric dentists reviewed 137 dental casts and recorded their opinion on whether orthodontic treatment was needed. RESULTS: We found a high level of agreement between pediatric dentists, orthodontists and general practitioners (Kappa range 0.86-0.95). Between the groups, the amount of agreement was lower. CONCLUSIONS: Orthodontists, general dental practitioners, and pediatric dentists in this sample exhibit high levels of agreement on orthodontic treatment need.

Attitude of Health Personnel↗

Cross-talk between alpha(4)beta(1)/alpha(5)beta(1) and c-Kit results in opposing effect on growth and survival of hematopoietic cells via the activation of focal adhesion kinase, mitogen-activated protein kinase, and Akt signaling pathways.

Erythroid progenitor cells (EPCs) are deficient in mice lacking either the ligand stem cell factor (SCF), its receptor c-Kit, or beta(1)-integrins. In nonhematopoietic cells, integrins and receptor tyrosine kinases can collaborate to modulate cellular functions, providing evidence for cross-talk between signals emerging from these cell surface molecules. Using specific recombinant fibronectin peptides that contain the binding site for the integrin alpha(4)beta(1) (FN-H296) or alpha(5)beta(1) (FN-CH271) or both alpha(4)beta(1) and alpha(5)beta(1) (FN-CH296), this study investigated the effect of adhesion alone, or in combination with activation of c-Kit, on functional and biochemical outcomes in an EPC line, G1E-ER2, and primary EPCs. G1E-ER2 cells and primary EPCs cultured on FN-CH271 in the presence of c-Kit activation led to a significant increase in proliferation in comparison with cells grown on FN-H296 or FN-CH296. G1E-ER2 cells cultured on FN-H296 or FN-CH296 resulted in significant cell death in comparison to cells grown on FN-CH271. Activation of c-Kit enhanced the survival of G1E-ER2 cells grown on FN-H296 or FN-CH296; however, the rescue was only partial. The reduced survival of G1E-ER2 cells on FN-H296 correlated with reduced activation of Akt and expression of Bcl-2 and Bcl-x(L), whereas increase in proliferation on FN-CH271 correlated with significantly enhanced and sustained activation of focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) pathways. These data demonstrate that adhesion-induced signals emanating from ligation of alpha(4)beta(1) and alpha(5)beta(1) result in distinct biologic outcomes, including death via alpha(4)beta(1) and survival/proliferation via alpha(5)beta(1). (Blood. 2001;97:1975-1981)

Animals↗

A novel mechanism of cooperation between c-Kit and erythropoietin receptor. Stem cell factor induces the expression of Stat5 and erythropoietin receptor, resulting in efficient proliferation and survival by erythropoietin.

Optimal production of red cells in vivo requires collaboration between c-Kit, erythropoietin receptor (Epo-R), and GATA-1. However, the mechanism(s) of collaboration remain unclear. Utilizing an embryonic stem cell-derived erythroid progenitor cell line from mice deficient in GATA-1, we have examined the role of c-Kit and Epo-R in erythroid cell proliferation, survival, and differentiation. In the absence of GATA-1, we demonstrate an essential role for c-Kit in survival and proliferation of erythroid progenitors via the regulation of Bcl-2 expression. In addition, we demonstrate that Epo-R and Stat5 are regulated by a second, novel mechanism. We demonstrate that c-Kit stimulation by stem cell factor is essential for the maintenance of Epo-R and Stat5 protein expression, which results in significantly enhanced Bcl-x(L) induction and survival of erythroid progenitors in response to Epo stimulation. Restoration of GATA-1 function results in terminal erythroid maturation and up-regulation of Epo-R and Bcl-x(L) expression, leading also to significantly enhanced survival of terminally differentiating erythroid progenitors in the presence of only Epo. These results demonstrate that c-Kit and Epo-R have unique role(s) during distinct phases of erythroid maturation, and both stem cell factor and Epo contribute to the regulation of the Epo-R-Stat5-Bcl-x(L) pathway to ensure optimal survival, proliferation, and differentiation of erythroid progenitors.

Animals↗

Complex proximal humeral fractures in adults--a systematic review of management.

We performed a systematic review of the literature to compare the clinical outcomes of the management of three and four part fractures of the proximal humerus by conservative regimes, internal and external fixations and arthroplasty. We identified 147 reports of comparative trials and case series between 1969 and 1999. We selected only studies dealing exclusively with three and four part fractures of the proximal humerus, with at least 15 patients, treated within 48 h of injury by one of the three modalities studied, in which at least one of the outcomes of interest (pain, range of motion, infection and restoration of anatomy) was described. Also, to be included, studies had to have a follow-up period of at least 6 months, in which a minimum of 85% of patients were followed-up. Twenty four reports met our eligibility criteria. Conservatively managed patients had more pain and a poorer range of motion than those managed by either fixation or arthroplasty. Better restoration of anatomy was delivered in the fixation group. There was no significant difference in the functional range of motion between the arthroplasty and fixation groups, but there were very few studies available to compare infection rates in these two management modalities. The results from the present systematic review suggest that the data from the published literature are inadequate for evidence-based decision making with regards to the treatment of complex proximal humeral fractures.

Arthroplasty↗

Topographical and physicochemical modification of material surface to enable patterning of living cells.

Precise control of the architecture of multiple cells in culture and in vivo via precise engineering of the material surface properties is described as cell patterning. Substrate patterning by control of the surface physicochemical and topographic features enables selective localization and phenotypic and genotypic control of living cells. In culture, control over spatial and temporal dynamics of cells and heterotypic interactions draws inspiration from in vivo embryogenesis and haptotaxis. Patterned arrays of single or multiple cell types in culture serve as model systems for exploration of cell-cell and cell-matrix interactions. More recently, the patterned arrays and assemblies of tissues have found practical applications in the fields of Biosensors and cell-based assays for Drug Discovery. Although the field of cell patterning has its origins early in this century, an improved understanding of cell-substrate interactions and the use of microfabrication techniques borrowed from the microelectronics industry have enabled significant recent progress. This review presents the important early discoveries and emphasizes results of recent state-of-the-art cell patterning methods. The review concludes by illustrating the growing impact of cell patterning in the areas of bioelectronic devices and cell-based assays for drug discovery.

Animals↗

Cholecystogastric fistula: laparoscopic repair.

We describe a patient with a cholecystogastric fistula treated by the laparoscopic approach. The use of intracorporeal suturing allows laparoscopic management of cholecystogastric fistulae without the need for an endoscopic transecting stapler.

Adult↗

Rac2 stimulates Akt activation affecting BAD/Bcl-XL expression while mediating survival and actin function in primary mast cells.

Mast cells generated from Rac2-deficient (-/-) mice demonstrated defective actin-based functions, including adhesion, migration, and degranulation. Rac2(-/-) mast cells generated lower numbers and less mast cell colonies in response to growth factors and were deficient in vivo. Rac2(-/-) mast cells demonstrated a significant reduction in growth factor-induced survival, which correlated with the lack of activation of Akt and significant changes in the expression of the Bcl-2 family members BAD and Bcl-XL, in spite of a 3-fold induction of Rac1 protein. These results suggest that Rac2 plays a unique role in multiple cellular functions and describe an essential role for Rac2 in growth factor-dependent survival and expression of BAD/Bcl-XL.

Actins↗

Characterization and targeted disruption of murine Nup50, a p27(Kip1)-interacting component of the nuclear pore complex.

p27(Kip1) is a member of the Cip-Kip family of cyclin-dependent kinase (Cdk) inhibitors that binds to cyclin-Cdk complexes and inhibits their catalytic activity in response to antiproliferative stimuli. p27(Kip1) is regulated by several posttranscriptional mechanisms, including subcellular localization. We have identified a component of the nuclear pore complex (NPC), termed Nup50, through its two-hybrid interactions with p27(Kip1). Nup50 is a nucleoplasmically oriented component of the nuclear pore complex with a role in protein export (T. Guan, R. H. Kehlenbach, E. C. Schirmer, A. Kehlenbach, F. Fan, B. E. Clurman, N. Arnheim, and L. Gerace, Mol. Cell. Biol. 20:5619-5630, 2000). We found that murine Nup50 is a widely expressed nucleoporin and that Nup50 expression is highest in the developing neural tube and adult testes. We have also examined interactions between Nup50 and the NPC and found specific two-hybrid interactions between Nup50 and several well-defined components of the NPC, as well as coimmunoprecipitation of Nup50 with the nucleoporin Nup153 from transfected mammalian cells. In order to study Nup50 function in vivo, we cloned the mouse Nup50 genomic locus and created a targeted Nup50 deletion in the mouse germ line. Nup50 disruption resulted in a complex phenotype characterized by late embryonic lethality, neural tube defects, and intrauterine growth retardation. Although Nup50-null mouse embryo fibroblasts exhibited no defects in either cell cycle control or p27(Kip1) regulation, Nup50 deletion was associated with abnormalities in p27(Kip1) expression and cell proliferation in the developing neuroepithelium. We conclude that Nup50 is a nucleoporin with essential functions during mouse development.

Amino Acid Sequence↗

The presence of novel amino acids in the cytoplasmic domain of stem cell factor results in hematopoietic defects in Steel(17H) mice.

Stem cell factor (SCF) is expressed as an integral membrane growth factor that may be differentially processed to produce predominantly soluble (S) (SCF(248)) or membrane-associated (MA) (SCF(220)) protein. A critical role for membrane presentation of SCF in the hematopoietic microenvironment (HM) has been suggested from the phenotype of the Steel-dickie (Sl(d)) mice, which lack MA SCF, and by studies performed in our laboratory (and by others) using long-term bone marrow cultures and transgenic mice expressing different SCF isoforms. Steel(17H) (Sl(17H)) is an SCF mutant that demonstrates melanocyte defects and sterility in males but not in females. The Sl(17H) allele contains a intronic mutation resulting in the substitution of 36 amino acids (aa's) in the SCF cytoplasmic domain with 28 novel aa's. This mutation, which affects virtually the entire cytoplasmic domain of SCF, could be expected to alter membrane SCF presentation. To investigate this possibility, we examined the biochemical and biologic properties of the Sl(17H)-encoded protein and its impact in vivo and in vitro on hematopoiesis and on c-Kit signaling. We demonstrate that compound heterozygous Sl/Sl(17H) mice manifest multiple hematopoietic abnormalities in vivo, including red blood cell deficiency, bone marrow hypoplasia, and defective thymopoiesis. In vitro, both S and MA Sl(17H) isoforms of SCF exhibit reduced cell surface expression on stromal cells and diminished biological activity in comparison to wild-type (wt) SCF isoforms. These alterations in presentation and biological activity are associated with a significant reduction in the proliferation of an SCF-responsive erythroid progenitor cell line and in the activation of phosphatidylinositol 3-Kinase/Akt and mitogen-activated protein-Kinase signaling pathways. In vivo, transgene expression of the membrane-restricted (MR) (SCF(X9/D3)) SCF in Sl/Sl(17H) mutants results in a significant improvement in peripheral red blood cell counts in comparison to Sl/Sl(17H) mice.

Amino Acid Sequence↗

Frictional resistance in orthodontic brackets with repeated use.

This study measured and compared the level of frictional resistance generated with a nonrepeated and repeated experimental design to evaluate whether the wear in the bracket slot will influence frictional resistance. Both 0.018 and 0.022 inch slot size edgewise brackets were tested in a specially designed apparatus. The frictional resistance was measured on an Instron Universal Testing Machine. A repeated measures ANOVA was used to determine differences among the 10 individual bracket wire specimens for each combination to study the influence of wear on static and kinetic frictional force. A paired t test (two-tail) procedure was used to compare the static and kinetic frictional forces in the nonrepeated and repeated study for each bracket slot, wire size, and bracket type. The results show that there was a distinct trend for the mean frictional force to be higher with the repeated use of the brackets.

Analysis of Variance↗

Comparison of frictional resistance in titanium and stainless steel brackets.

This study measures and compares the level of frictional resistance generated between titanium and stainless steel brackets. Both 0.018 and 0.022 inch slot size edgewise brackets were tested with different sized rectangular stainless steel wires in a specially designed apparatus. The frictional resistance was measured on Instron Universal testing machine (Instron Corp, Canton, Mass) with a 10 pound load cell. The specimen population was composed of 180 brackets and 180 wire specimens. A completely randomized design (one way) ANOVA was used to test for significant differences among the three bracket/wire types in the 0.018 and 0.022 inch slot sizes. This was followed by the Student Newman Keuls Multiple Comparison of means ranking at P < .05 to determine differences between the different groups. The titanium brackets showed lower static and kinetic frictional force as the wire size increased, whereas stainless steel brackets showed higher static and kinetic frictional force as the wire size increased.

Analysis of Variance↗

Comparison of load transmission and bracket deformation between titanium and stainless steel brackets.

This study measures the load transmitted and structural integrity of stainless steel and titanium brackets on application of torsional forces. Both 0.018 and 0.022 inch slot size edgewise brackets were tested in a specially designed apparatus that applied a torque value of 45 degrees. The load generated was measured by an Instron Universal Testing Machine at intervals of 15 degrees, 30 degrees, and 45 degrees of torque application. The structural stability of the brackets was evaluated by measuring the bracket slot width with a traveling stereoscopic microscope before and after the brackets were subjected to torsional forces. The specimen population was composed of 80 brackets and 80 wire specimens. An independent sample t test was used for comparison of mean load generated at 45 degrees of torque application. Repeated measures ANOVA (one-way) comparison was used to evaluate changes in load at different torque levels for the stainless steel and titanium brackets. A paired t test (two-tail) was used to determine the difference between initial and final bracket slot width at 45 degrees of torque applied for the two bracket types. The titanium brackets transmitted higher loads at 15 degrees and 30 degrees torque and lower load at 45 degrees torque on application of torsional forces in comparison to stainless steel brackets. The titanium brackets demonstrated superior dimensional stability compared to stainless steel brackets (P < .0001).

Analysis of Variance↗

Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense.

In mammals, the Rho family GTPase Rac2 is restricted in expression to hematopoietic cells, where it is coexpressed with Rac1. Rac2-deficient mice were created to define the physiological requirement for two near-identical Rac proteins in hematopoietic cells. rac2-/- neutrophils displayed significant defects in chemotaxis, in shear-dependent L-selectin-mediated capture on the endothelial substrate Glycam-1, and in both F-actin generation and p38 and, unexpectedly, p42/p44 MAP kinase activation induced by chemoattractants. Superoxide production by rac2-/- bone marrow neutrophils was significantly reduced compared to wild type, but it was normal in activated peritoneal exudate neutrophils. These defects were reflected in vivo by baseline neutrophilia, reduced inflammatory peritoneal exudate formation, and increased mortality when challenged with Aspergillus fumigatus. Rac2 is an essential regulator of multiple specialized neutrophil functions.

Actins↗

Electrical, chemical, and topological addressing of mammalian cells with microfabricated systems.

This communication describes our work in electrical, topological, and chemical micromodification of surfaces to modulate cellular form and function. We have addressed the surface physico-chemico-mechano properties of cell culture substrates that play a role in modulating cellular behavior. Single factorial model systems have been built using techniques adapted from microlithography. The tools and techniques of microfabrication, if harnessed and used correctly, can be enabling in elucidating the underlying principles and fundamental forces driving the cell-substrate interface. Additionally, the long-term practical applications of microfabrication in medicine and biomaterial/tissue engineering lie in enabling "communication" with living cells/tissues at the cellular and subcellular levels.

Animals↗