Search PubMed⌕ Search

Biomedical subjects

K M Smith

Publications and source records attributed to K M Smith.

At least 37 records · Page 2Linked to original sources
PubMed2001

Internalizing and externalizing behavior of children with enlisted Navy mothers experiencing military-induced separation.

OBJECTIVES: To examine whether children with Navy mothers exhibit higher levels of internalizing and externalizing behavior than children in civilian families and whether deployment affects children's internalizing and externalizing behavior. METHOD: Navy mothers who experienced deployment completed a measure assessing children's internalizing and externalizing behavior before and after a deployment (and at similar intervals for the Navy and civilian comparison groups). Data collection took place between 1996 and 1998. RESULTS: Navy children with deployed mothers exhibited higher levels of internalizing behavior than children with nondeployed Navy mothers. Navy children whose mothers experienced deployment were more likely to exhibit clinical levels of internalizing behavior than Navy children with nondeployed mothers or civilian children. Group differences, however, were modest and overall mean scores were in the normal range. CONCLUSIONS: Findings do not suggest greater pathology in children of Navy mothers; however, findings do indicate we should be particularly attentive of deployed mothers and their children.

Adult↗
PubMed2001

The role of the peripheral benzodiazepine receptor in the apoptotic response to photodynamic therapy.

Several previous studies have suggested that the peripheral benzodiazepine receptor (PBR) on the mitochondrial surface was an important target for photodynamic therapy (PDT). In this study we compared PBR affinity vs photodynamic efficacy of protoporphyrin-IX (PP-IX) and two structural analogs, PP-III and PP-XIII, using murine leukemia L1210 cells in culture. The results indicate that the three agents have approximately equal hydrophobicity, affinity for L1210 cells and ability to initiate photodamage leading to an apoptotic response. But only PP-IX had significant affinity for the PBR. These data indicate that the relationship between PDT efficacy and PBR affinity may hold only for sensitizers with the PP-IX configuration.

Animals↗
PubMed2001

Gender-specific issues in the treatment of migraine.

Migraine is approximately three times more common in women than in men. Women tend to have longer attacks and are more likely than men to experience aura with migraine, but both sexes can experience frequent and severe attacks. Treatment principles for migraine and guidelines for the use of prophylactic and abortive therapies are generally consistent between males and females. However, due to hormonal changes induced in the female during menstruation, oral contraceptive use, pregnancy, and menopause, gender-specific therapeutic strategies are often necessary when treating migraine in females.

Contraceptives, Oral↗
PubMed2001

Evaluation and management of high ankle sprains.

Owing to the variability of injury, a mechanism of injury other than external rotation of the foot should not rule out a high ankle sprain. One must consider syndesmotic injury in the differential diagnosis of common ankle sprains and trauma. A high index of suspicion must lead the physician through clinical and radiographic examinations. Early and appropriate treatment of a high ankle sprain can greatly decrease a prolonged return to activity. Patients, especially competitive atheletes, must be educated regarding the morbidity of the condition.

Ankle↗
PubMed2001

CCL18/DC-CK-1/PARC up-regulation in hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a lung inflammatory disorder characterized by accumulation of T lymphocytes. However, the mechanisms implicated in this process remain undefined. We examined the expression of dendritic cell (DC)-derived CC chemokine 1 (CK1)/CCL18, a chemokine putatively involved in naive T cell recruitment, in lungs from 10 patients with HP, 9 patients with idiopathic pulmonary fibrosis (IPF), and 20 healthy lungs. CCL18 was measured by real-time quantitative PCR and localized in lungs by in situ hybridization and immunohistochemistry. CCL18 expression was significantly increased in lungs affected by HP in comparison with lungs affected by IPF (2,085+/-393 vs. 1,023+/-110; P<0.05) and controls (2,085+/-393 vs. 467+/-94; P<0.01). Macrophages, DCs, and alveolar epithelial cells were the main sources of CCL18. There was a direct correlation between the levels of tissue CCL18 and the number of lymphocytes in the bronchoalveolar lavage fluids. High levels of CCL18 were detected in the subacute rather than the chronic phase of HP. These findings suggest a role for CCL18 in the pathogenesis of HP.

Alveolitis, Extrinsic Allergic↗
PubMed2001

Women and heart disease: the treatment may end but the suffering continues.

Though heart disease is the number one health problem among women, men continue to represent the majority of those in cardiac rehabilitation for secondary prevention. Research has shown that conventional rehabilitation programs do not meet the needs of women recovering from cardiac events. Women's primary rehabilitative need may be support, particularly from women with similar experiences. Furthermore, the need for support in living with heart disease may persist beyond the in-hospital phase of recovery. The purpose of this study was to develop and implement a community-based communication and psycho-educational support group for women with heart disease. Participatory action research was the methodology selected. Two groups of women (n = 16) met monthly for 5 months to develop the program. Sessions were facilitated jointly by a nurse clinician and a nurse-researcher. Between sessions, participants kept diaries of their experiences. Data consisted of videotapes and transcriptions of the sessions, field notes, and the women's diaries and final evaluation. Initial analysis revealed that the value of the group for the women was threefold: it helped them to cope with their emotional reactions, offered social support, and helped them to manage their health problem. Iterative analysis unveiled a meta-paradigm consistent with the concept of suffering. The apparent overall benefit of a community-based psycho-educational support group for women with heart disease is acknowledgement and sharing of suffering, something that cannot readily occur in women's other life arenas.

Adaptation, Psychological↗
PubMed2000

Survey of ASHP-accredited pharmacy residency programs.

The results of a survey of the requirements and features of pharmacy residency programs are reported. The survey was mailed on March 5, 1999, to the directors of 414 pharmacy practice and specialty residency programs with ASHP accreditation as of March 1, 1999. Included were questions on stipends, staffing requirements, and benefits. Information not typically included in the ASHP residency directories was also sought. Three hundred surveys were returned, for a 72% response rate. Of the responding programs, 174 (58%) were pharmacy practice programs and the rest specialty programs. The specialties with the largest number of respondents were primary care (30 of 126, or 24%) and drug information (23, or 18%). The practice setting varied widely, but a university-based practice site was most frequent (122 of 300 programs, or 41%). The overall median stipend range was $28,000-$28,999; stipends varied relatively little by geographic region but were highest in New York and New Jersey. Most residency programs had a staffing requirement, which averaged eight hours per week. A substantial part of residents' time was spent on drug distribution and patient care activities, such as medical rounds and patient counseling. The most common benefits reported were paid time off, health and medical coverage, and reimbursement for specific professional expenses. Ultimately, the creation of an Internet-accessible electronic database will maximize the availability and timeliness of such information and minimize the cost and labor involved in updating currently available resources. A survey of ASHP-accredited residency programs yielded data that provide a valuable supplement to the information in ASHP residency directories.

Accreditation↗
PubMed2000

Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib).

The human concentrative (Na(+)-linked) plasma membrane transport proteins hCNT1 and hCNT2 are selective for pyrimidine nucleosides (system cit) and purine nucleosides (system cif), respectively. Both have homologs in other mammalian species and belong to a gene family (CNT) that also includes hfCNT, a newly identified broad specificity pyrimidine and purine Na(+)-nucleoside symporter (system cib) from the ancient marine vertebrate, the Pacific hagfish (Eptatretus stouti). We now report the cDNA cloning and characterization of cib homologs of hfCNT from human mammary gland, differentiated human myeloid HL-60 cells, and mouse liver. The 691- and 703-residue human and mouse proteins, designated hCNT3 and mCNT3, respectively, were 79% identical in amino acid sequence and contained 13 putative transmembrane helices. hCNT3 was 48, 47, and 57% identical to hCNT1, hCNT2, and hfCNT, respectively. When produced in Xenopus oocytes, both proteins exhibited Na(+)-dependent cib-type functional activities. hCNT3 was electrogenic, and a sigmoidal dependence of uridine influx on Na(+) concentration indicated a Na(+):uridine coupling ratio of at least 2:1 for both hCNT3 and mCNT3 (cf 1:1 for hCNT1/2). Phorbol myristate acetate-induced differentiation of HL-60 cells led to the parallel appearance of cib-type activity and hCNT3 mRNA. Tissues containing hCNT3 transcripts included pancreas, bone marrow, trachea, mammary gland, liver, prostate, and regions of intestine, brain, and heart. The hCNT3 gene mapped to chromosome 9q22.2 and included an upstream phorbol myristate acetate response element.

Amino Acid Sequence↗
PubMed2000

Th1 and Th2 CD4+ T cells provide help for B cell clonal expansion and antibody synthesis in a similar manner in vivo.

The relative ability of Th1 and Th2 T cells to help B cells remains controversial as do the mechanisms by which both T cell subsets provide help in vivo. Whether this help affects the clonal expansion and/or differentiation of B cells has been difficult to assess due to the low frequency of Ag-specific T and B lymphocytes. We have employed a novel technique to directly monitor the clonal expansion of Ag-specific T and B lymphocytes in vivo. OVA-specific TCR transgenic T lymphocytes were polarized toward a Th1 or Th2 phenotype in vitro. These cells were then transferred into syngeneic recipients, along with B cell receptor transgenic hen egg lysozyme-specific B lymphocytes. Our results indicate that Th1 and Th2 cells support B cell responses to a similar extent in vivo and that they achieve this in the same manner by migrating into B cell follicles to promote CD154-dependent B cell clonal expansion and Ab production.

Adoptive Transfer↗
PubMed2000

Oocyte development in Hydra involves selection from competent precursor cells.

We have investigated oocyte development in Hydra vulgaris, a member of one of the oldest metazoan phyla. We show that oocyte determination involves a mechanism that establishes a subset of precursor interstitial cells competent to differentiate into oocytes. The oocyte is singled out from this subset and the competence of the remaining cells to become oocytes dramatically decreases as they adopt the alternative nurse cell fate. Progression through the nurse cell differentiation program requires the presence of the oocyte. When the oocyte is removed from the egg field, nurse cells abort their differentiation program, undergo apoptosis, and are phagocytosed and degraded by somatic epithelial cells. However, in the presence of the oocyte, nurse cells differentiate and enter an unusual apoptosis program where they are phagocytosed by the oocyte, but are not degraded. We show that the oocyte is able to induce this unusual apoptosis program in immature nurse cells that have not completed differentiation. A new model for oocyte development in Hydra is discussed.

Animals↗
PubMed2000

Transgenic expression of Ly-49A in thymocytes alters repertoire selection.

A T cell-specific Ly-49A transgene inhibits TCR-mediated activation in the presence of H-2Dd. Expression of this transgene by developing thymocytes impairs negative selection evidenced by a failure to delete potentially autoreactive T cells and development of a graft-vs-host-disease-like syndrome. In mice carrying both the Ly-49A and a class II-restricted TCR transgene, positive selection was lost, but only when H-2Dd was present on thymic epithelium. These results are consistent with models suggesting that thymic selection is dependent on the perceived intensity of TCR signaling. More interestingly, these results show that Ly-49A does not simply provide a strict on/off switch for T cell responses. Since Ly-49A may shift the signaling threshold of TCR-induced triggering, inducible expression of Ly-49A may regulate peripheral memory/activated T cells by raising the threshold for T cell reactivation.

Animals↗
PubMed2000

Oral tolerance.

The intestinal immune system discriminates between potentially harmful and harmless foreign proteins. The basis for this differential response may be related to the conditions of antigen presentation by antigen-presenting cells, as determined by their phenotype or activation state. How these conditions affect specific immunologic unresponsiveness to later challenge with an antigen is not known. Two possible mechanisms are the induction of anergy or deletion of responsive cells and the activation of regulatory cells or mediators, and the mechanism may very depending on the tolerizing regimen used. Should regulatory cells be involved, they are speculated to induce tolerance through their production of inhibitory cytokines, such as IL-4, IL-10, and TGF-beta. Studies using specific antibodies and selective genetic knockout (KO) strains of mice, however, have provided conflicting data. A final intriguing possibility is that tolerance results from cognate interactions between T cells and APCs, so that tolerant T cells or APCs prime T cells they contact to deliver a tolerogenic signal to the next T cell they encounter, possibly through a function dependent on interactions between Notch family receptors and their ligands. As with many questions in mucosal immunology, definition of the mechanisms of oral tolerance (OT) has proved difficult to address experimentally, but promising approaches include study of the distribution of fed antigen, of targeted genetic KOs, and of transgenic strains.

Animals↗
PubMed2000

HyAlx, an aristaless-related gene, is involved in tentacle formation in hydra.

Developmental gradients are known to play important roles in axial patterning in hydra. Current efforts are directed toward elucidating the molecular basis of these gradients. We report the isolation and characterization of HyAlx, an aristaless-related gene in hydra. The expression patterns of the gene in adult hydra, as well as during bud formation, head regeneration and the formation of ectopic head structures along the body column, indicate the gene plays a role in the specification of tissue for tentacle formation. The use of RNAi provides more direct evidence for this conclusion. The different patterns of HyAlx expression during head regeneration and bud formation also provide support for a recent version of a reaction-diffusion model for axial patterning in hydra.

Amino Acid Sequence↗
PubMed2000

PCR detection of host and HIV-1 sequences from archival brain tissue.

Mutations in CCR5 and CCR2b have been recently shown to affect disease progression towards AIDS. A role for these host genotypes in AIDS dementia complex (ADC) has also been postulated but remains unclear. Additionally, brain-derived envelope sequences from HIV-1 have been associated with ADC but their specific contribution to pathogenesis remains uncertain. This study demonstrates the successful use of PCR techniques to isolate host CCR5 and CCR2b, and HIV-1 V3 sequences from paraffin embedded tissues from patients with and without ADC. PCR amplification from archival tissue offers a novel approach for studying the interactions between potential neuroprotective elements in the host and virulence determinants in HIV that may contribute to differences in susceptibility to ADC.

AIDS Dementia Complex↗
PubMed2000

Mycotic infections. Effective management of conditions involving the skin, hair, and nails.

Superficial mycotic infections of the skin, hair, or nails are recurring presentations in the geriatric primary care setting. The most common infections are those caused by dermatophytes. The genus Trichophyton gives rise to most of the tinea dermatophytoses, including tinea capitis, tinea pedis, and tinea unguium (onychomycosis). Part of the diagnostic challenge lies in distinguishing the mycotic lesions from those caused by cutaneous diseases such as psoriasis, eczema, dyshidrosis, and contact dermatitis. Because environmental conditions play a major role in fungal infection onset, clinical management should include patient education about conditions conducive to fungal propagation. Oral agents are the primary mode of treatment for fungal infections of the scalp and nails, whereas topical treatments are frontline agents for other superficial skin conditions.

Antifungal Agents↗
PubMed1999

Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters.

BACKGROUND: Gemcitabine, a pyrimidine analogue of deoxycytidine, is an anticancer nucleoside drug that requires functional plasma membrane nucleoside transporter proteins to reach its intracellular targets and cause cytotoxicity. Because of technical difficulties inherent in studying nucleoside transport in human cells, we rigorously defined gemcitabine membrane transportability by producing each of the available human (h) and rat (r) recombinant nucleoside transporters (NTs) individually in Xenopus laevis oocytes. METHODS: Oocytes were microinjected with in vitro-transcribed RNAs derived from complementary DNAs encoding (C = concentrative) rCNT1, rCNT2, hCNT1, hCNT2, (E = equilibrative) rENT1, rENT2, hENT1, and hENT2. Uptake of [(3)H]gemcitabine and [(14)C] uridine was measured 3 days after microinjection to determine kinetic constants. We also used the two-electrode, voltage-clamp technique to investigate the electrophysiology of hCNT1-mediated gemcitabine transport. RESULTS: Gemcitabine was transported by most of the tested proteins (the exceptions being the purine-selective rCNT2 and hCNT2), with the greatest uptake occurring in oocytes producing recombinant rCNT1 and hCNT1. Influxes of gemcitabine mediated by hCNT1, hENT1, and hENT2 were saturable and conformed to Michaelis-Menten kinetics with apparent K(m) values of 24, 160, and 740 microM, respectively. Gemcitabine had a limited ability to cross the lipid bilayer of oocyte membranes by simple diffusion. External application of gemcitabine to oocytes producing recombinant hCNT1 induced an inward current, which demonstrated that hCNT1 functions as a Na(+)/nucleoside co-transport protein and confirmed the transporter's ability to transport gemcitabine. CONCLUSIONS: Mammalian nucleoside transporters vary widely in their affinity and capacity to transport gemcitabine. Variation in the tumor and tissue distribution of plasma membrane nucleoside transporter proteins may contribute to the solid tumor activities and schedule-dependent toxic effects of gemcitabine.

Animals↗