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Biomedical subjects

K Daniels

Publications and source records attributed to K Daniels.

At least 37 records · Page 2Linked to original sources
PubMed1999

Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1) are allelic disorders caused by mutations in the gene encoding cartilage oligomeric matrix protein (COMP). PSACH is a dominant condition characterized by disproportionate short stature, joint laxity, and early-onset osteoarthritis. EDM1 is a less severe skeletal dysplasia associated with average to mild short stature, joint pain, and early-onset osteoarthritis. COMP is an extracellular matrix protein present in cartilage, ligament, and tendon tissues. Here, we report on nine novel mutations in COMP causing PSACH and EDM1. Four of these mutations are in exons 13C and 14 where no previous mutations had been reported. One of those mutations was identified in two separate EDM1 families. In addition, we have identified the first case of PSACH resulting from an expansion of the five aspartates in exon 17B. We are also reporting a mutation in a third PSACH family with somatic/germline mosaicism. Therefore, this report increases the range of mutations that cause PSACH and EDM1 and provides additional regions to target for mutational analysis.

Achondroplasia↗
PubMed1999

The home as a workplace: work-family interaction and psychological well-being in telework.

Home-based telework is a growing phenomenon with great potential to affect employees' psychological well-being. Although prior studies show both positive and negative effects on work-family interaction, conclusions are limited by the way telework, well-being, and work-family interaction have been modeled. The authors present a conceptual framework that describes telework as a multidimensional phenomenon and separates the effects of the home environment from those of distance from the organization. Propositions concerning work-family interaction are developed from P. Warr's (1987) model of the environmental antecedents of well-being, prior telework studies, and the work-family literature. Spillover between work and nonwork domains of well-being is discussed, and suggestions for future research on this complex issue are presented.

Family Relations↗
PubMed1999

Misexpression of the opaque-phase-specific gene PEP1 (SAP1) in the white phase of Candida albicans confers increased virulence in a mouse model of cutaneous infection.

Candida albicans WO-1 switches reversibly and at high frequency between a white and an opaque colony-forming phenotype that includes dramatic changes in cell morphology and physiology. A misexpression strategy has been used to investigate the role of the opaque-phase-specific gene PEP1 (SAP1), which encodes a secreted aspartyl proteinase, in the expression of the unique opaque-phase phenotype and phase-specific virulence in two animal models. The PEP1 (SAP1) open reading frame was inserted downstream of the promoter of the white-phase-specific gene WH11 in the transforming vector pCPW7, and the resulting transformants were demonstrated to misexpress PEP1 (SAP1) in the white phase. Misexpression did not confer any of the unique morphological characteristics of the opaque phase to cells in the white phase and had no effect on the switching process. However, misexpression conferred upon white-phase cells the increased capacity of opaque-phase cells to grow in medium in which protein was the sole nitrogen source. Misexpression of PEP1 (SAP1) had no effect on the virulence of white-phase cells in a systemic mouse model, in which white-phase cells were already more virulent than opaque-phase cells. Misexpression did, however, confer upon white-phase cells the dramatic increase in colonization of skin in a cutaneous mouse model that was exhibited by opaque-phase cells. Misexpression of PEP1 (SAP1) conferred upon white-phase cells two dissociable opaque-phase characteristics: increased adhesion and the capacity to cavitate skin. The addition of pepstatin A to the cutaneous model inhibited the latter, but not the former, suggesting that the latter is effected by released enzyme, while the former is effected by cell-associated enzyme.

Animals↗
PubMed1998

Identification of twelve mutations in cartilage oligomeric matrix protein (COMP) in patients with pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is an autosomal dominant dwarfing condition characterized by disproportionate short stature, joint laxity, and early-onset osteoarthrosis. PSACH is caused by mutations in the gene encoding cartilage oligomeric matrix protein (COMP). We are reporting on mutations in COMP in 12 patients with PSACH, including ten novel mutations. Eleven of the mutations are in exons 17A, 17B, and 18A, which encode the calcium-binding domains, and one mutation is in exon 19, which encodes part of the carboxy-terminal globular domain. Two of the mutations identified are the common delGAC(1430-1444) in exon 17B, which accounts for 36% of identified PSACH mutations. This report increases the range of mutations in COMP that cause PSACH and provides additional evidence for the importance of the calcium-binding domains and the globular domain to the function of COMP.

Achondroplasia↗
PubMed1998

The invasive and destructive behavior of HIV-induced T cell syncytia on collagen and endothelium.

HIV-induced syncytia of the CD4+ SUP-T1 T cell line mimic the subcellular organization of single cells and are able to crawl like single cells through extension of giant pseudopods. Because syncytia have been demonstrated in lymphoid tissue of HIV-positive individuals, their behavior has been investigated on more natural substrata, including dehydrated collagen, hydrated collagen, endothelial monolayers, and endothelial monolayers grown on collagen cushions. On hydrated collagen gels, both individual SUPT1 cells and syncytia form unusually long cylindrical projections that possess pseudopodial ends and are highly dynamic. Syncytia penetrate collagen gels through extension of these projections and disrupt their integrity. When incubated on endothelium, both single cells and syncytia readily traverse the monolayer through holes, and when incubated on endothelium supported by a collagen cushion, syncytia generate large holes through the monolayer, penetrate the monolayer, and disrupt the collagen gel through extension of long, complex projections. Invading syncytia also release viruses in a polarized fashion which adhere to and are taken up in vesicles by the endothelium. It is suggested that the destructive behaviors of syncytia which have been demonstrated in vitro may have correlates in vivo.

Actins↗
PubMed1998

Retention of cartilage oligomeric matrix protein (COMP) and cell death in redifferentiated pseudoachondroplasia chondrocytes.

Cartilage oligomeric matrix protein (COMP) is a large extracellular glycoprotein that is found in the territorial matrix surrounding chondrocytes. Two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1) are caused by mutations in the calcium binding domains of COMP. In this study, we identified two PSACH mutations and assessed the effect of these mutations on redifferentiated chondrocyte structure and function. We confirmed, in vitro, that COMP is retained in enormous cisternae of the rough endoplasmic reticulum (rER) and relatively absent in the PSACH matrix. The rER accumulation may compromise chondrocyte function, leading to chondrocyte death. Moreover, while COMP appears to be deficient in the PSACH matrix, the matrix appeared to be normal but the over-all quantity was reduced. These results suggest that the abnormality in linear growth in PSACH may result from decreased chondrocyte numbers which would also affect the amount of matrix produced.

Achondroplasia↗
PubMed1998

Alcohol and morbidity in the Lung Health Study.

OBJECTIVE: There is a well documented J-shaped relationship between alcohol consumption and mortality that is not fully understood. Differences between studies, particularly in the use of cigarette smoking as a covariate, may partially explain inconsistencies in findings. This study sought to clarify the nature of this alcohol-smoking-mortality relationship. METHOD: The Lung Health Study enrolled 5,887 (3,702 male; 95% white) cigarette smokers with airways obstruction, aged 35 to 60. Measures of smoking, drinking and body mass index were available annually over the 5-year duration of the study, and pattern of alcohol use and diastolic blood pressure were assessed at baseline. Heavy drinkers were excluded from the sample. Documented evidence of hospitalizations was used in establishing morbidity. Proportional hazards regression was used for analysis. RESULTS: A significant protective effect of moderate drinking was found among men, but not women. There was also no apparent interaction between smoking status and drinks per week (both time dependent) in these data on morbidity and mortality. A baseline pattern of drinking eight or more drinks per occasion, but less than once a month, among men was associated with fewer hospitalizations and deaths. CONCLUSIONS: This study confirmed the general relationships between use of alcohol and illness or death, but with a few unexpected results. Further investigation is needed to identify whether these unexpected findings were due to our somewhat unique sample, to our use of hospitalization as the primary outcome measure, or to other causes.

Administration, Inhalation↗
PubMed1997

Risk factors for hospitalization in a cohort with type 1 diabetes. Wisconsin Diabetes Registry.

The authors investigate the postonset hospitalization rate and risk factors during 1987-1994 in Wisconsin, in a population-based, incidence cohort followed from diagnosis of Type 1 diabetes mellitus at ages 0-29 (n = 577). The overall rate was 8.9 +/- 0.60 (standard error) per 100 person-years of diabetes, whereof 5.7 was due to hyperglycemia, 1.9 to hypoglycemia, and 1.3 to other and undetermined causes. Major risk factors for hospitalization were longitudinally measured glycosylated hemoglobin level (rate ratio = 1.5 per 2% increase, 95% confidence interval 1.4-1.7), black/other race (rate ratio = 1.9, 95% confidence interval 1.0-3.6), diagnosis in a non-university-based setting (rate ratio = 1.9, 95% confidence interval 1.2-3.2), female sex (rate ratio = 1.5, 95% confidence interval 1.0-2.4 at age 11), age in males (rate ratio = 0.6, 95% confidence interval 0.4-0.8 per 5-year increase), and public or no insurance up to 18 months postdiagnosis (rate ratio = 2.2, 95% confidence interval 1.1-4.4). For individuals less than 18 years, "black/other race" was replaced in the model by "having other than two biologic parents in the home" (rate ratio = 2.0, 95% confidence interval 1.1-3.5). Hence, hospitalization is common in children, adolescents, and young adults with diabetes, primarily for problems with glycemic control.

Adolescent↗
PubMed1997

Autologous bone marrow versus non-mobilized peripheral blood stem cell transplantation for lymphoid malignancies: a prospective, comparative trial.

Autologous transplantation using bone marrow stem cells (BMSC) or peripheral blood stem cells (PBSC) is widely used for non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). We report a randomized, comparative trial comparing BMSC vs. non-mobilized PBSC for responsive NHL or HD. Patients randomized to BMSC (n = 13) vs. PBSC (n = 15) had more rapid neutrophil recovery (median 23 vs. 30 days), RBC independence (25 vs. 62 days), platelet independence (24 vs. 54 days), and shorter hospital stay. However, neither relapse, overall survival, nor relapse-free survival were different receiving BMSC vs. PBSC (all P > .7). Concurrently, 54 others (34 BMSC, 20 PBSC) were assigned non-randomly because of resistant disease or marrow unsuitable for harvest and similar patterns of engraftment favoring BMSC over PBSC were observed. In the entire group, BMSC transplantation (n = 47) led to quicker neutrophil recovery (P = .02), RBC (P = .06), and platelet independence (P =.04) and earlier hospital discharge (P = .02) vs. PBSC (n = 35). No difference in relapse, overall, or relapse-free survival were observed using BMSC vs. PBSC. These data suggest that non-mobilized PBSC are a satisfactory alternative to BMSC in patients with unsuitable marrow; however, transplantation with non-mobilized PBSC was associated with slower hematologic recovery, and longer hospital stay. No difference in tumor recurrence rates was observed between the PBSC or BMSC recipients. Unprimed PBSC transplantation offered no clinical advantage to BMSC.

Adolescent↗
PubMed1997

Stressors, locus of control, and social support as consequences of affective psychological well-being.

Tests of the influence of affective psychological well-being on stressors, locus of control, and social support in a 1-month follow-up study of 210 male and 34 female British accountants is reported. There was a marginally significant association between the level of psychological symptoms and subsequent reports of intensity of quantitative workload stressors. A significant interaction between psychological symptoms and a measure of depression-enthusiasm was found to predict subsequent locus of control. The results indicate a differential pattern of associations between aspects of affective well-being and subsequent reports of social support. The results also indicate that initially more frequent stressors are associated with subsequently less intense stressors of the same type. The findings highlight the dynamic and reciprocal nature of the occupational stress process.

Accounting↗
PubMed1997

A paradigm leap.

Explore the source record for details and available documents.

Home Care Services, Hospital-Based↗
PubMed1996

Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study. Lung Health Study Research Group.

STUDY OBJECTIVE: To assess cardiovascular conditions and other side effects associated with the use of nicotine polacrilex (NP), 2 mg. DESIGN: A multicentered randomized control trial of early intervention for the prevention of COPD. SETTING: Ten university medical centers in the United States and Canada. PARTICIPANTS: Adult smoking volunteers with evidence of early COPD; 3,923 in intervention and 1,964 controls. INTERVENTION: Smoking cessation program, including NP. MEASUREMENTS: Data on hospitalizations were collected annually. Data on reported NP side effects were collected at 4-month intervals for intervention participants. RESULTS: The rates of hospitalization for cardiovascular conditions and cardiovascular deaths during the 5 years of the study were not related to use of NP, to dose of NP, or to concomitant use of NP and cigarettes. About 25% of NP users reported at least one side effect, but most were very minor and transient. Side effects associated with discontinuance of NP in 5% or more of users included headache, indigestion, mouth irritation, mouth ulcers, and nausea. There was no evidence that concomitant use of NP and cigarettes was associated with elevated rates of reported side effects. Participants in the smoking cessation intervention who received intensive levels of instruction and monitoring of NP use (initially at 12 meetings during 3 months) appeared to report significantly lower rates of side effects (dizziness, headache, and throat irritation) than control participants, presumed to have less instruction and monitoring. CONCLUSIONS: NP, as used in the Lung Health Study, appears to be safe and unrelated to any cardiovascular illnesses or other serous side effects.

Adult↗
PubMed1996

Related donor marrow transplant for chronic myeloid leukemia: patient characteristics predictive of outcome.

Pre-transplant characteristics of 137 consecutive patients (including 103 patients with one or more features suggesting advanced disease) undergoing related donor marrow transplant for chronic myeloid leukemia (CML) were analyzed to determine their association with outcome. Multivariate analysis identified increased recipient age (relative risk (RR) for patients over 30 years of relapse or death 2.37; P = 0.004), and longer interval between diagnosis and transplant (RR 1.20; P = 0.0001) as significant adverse influences on disease-free survival (DFS). The 5-year DFS for patients transplanted within 1 year of diagnosis (¿early transplant', n = 71) was significantly higher (51%) than that for patients transplanted beyond 1 year from diagnosis ('delayed transplant', n = 55) (34%; log rank P = 0.02). For early transplant patients, poor prognostic features included myelofibrosis (RR 3.53; P = 0.018), splenomegaly (RR 2.22; P = 0.029) and the use of a female donor (RR 3.16; P = 0.002). The 5-year DFS for patients transplanted within 1 year of diagnosis and without signs of advanced disease was 67%. The presence of increasing numbers of features suggesting acceleration prior to transplant had a cumulative adverse influence of DFS. The risk of relapse (5 year estimate 20%) was also independently and significantly increased in association with a longer interval from diagnosis to transplant (P = 0.012). Early transplant is an important influence on DFS and relapse after related donor transplant therapy for CML, although additional patient characteristics influencing outcome can be identified and may have cumulative adverse effects.

Adolescent↗
PubMed1996

Peripheral nerve extract effects on mesenchymal cells.

Several common congenital limb disorders are characterized by normal tissue differentiation but abnormal somatic growth. These include: idiopathic clubfoot, idiopathic leg length discrepancy, hemi-atrophy and hemi-hypertrophy. Both clinical and research studies have suggested that peripheral nerves may be important in regulating somatic growth of limb tissues. To investigate the hypothesis that peripheral nerves convey trophic substances to mesenchymal tissues that are involved in the regulation of growth, we developed an in vitro assay to assess the effect of fractions of peripheral nerve on myoblast and chondroblast growth and differentiation in a mammalian (rat) system. Whole rat sciatic nerve extract was fractionated by ammonium sulfate precipitation and by affinity chromatography. Concavalin A chromatography resolved whole nerve extract into a glycoprotein and a non-glycoprotein fraction. Serial ammonium sulfate precipitation yielded three pellet fractions designated as 35%, 70%, and 100% pellets; corresponding to ammonium sulfate concentrations of 0 to 35%, 35 to 70%, and 70 to 100% saturation, respectively. Dialyzed solutions of these pellets as well as the fractions from Concavalin A chromatography were assayed for biological activity in micromass cultures of rat limb bud mesenchyme, which allowed assessment of both myoblast and chondroblast stimulation. Stimulation of protein synthesis and myoblast proliferation (as measured by MF20 staining) occurred with both 70% and 100% ammonium sulfate fractions. Stimulation of chondroblasts (as measured by the number of alcian blue staining nodules) occurred with the 35% and 100% fractions. The glycoprotein fraction from the affinity chromatography stimulated protein synthesis and myoblast proliferation and inhibited chondroblast development. Stimulation of chondroblasts was seen with the non-glycoprotein fraction. No effect on protein synthesis, myoblast proliferation or chondroblast proliferation was found in cultures treated with rat transferrin (transferrin has been reported to stimulate myoblasts in avian culture systems).

Ammonium Sulfate↗