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Biomedical subjects

K Strand

Publications and source records attributed to K Strand.

At least 19 recordsLinked to original sources
PubMed2004

Frontotemporal lobar degeneration and ubiquitin immunohistochemistry.

We set out to determine the frequency of the different pathologies underlying frontotemporal degeneration (FTD) in our brain bank series, by reviewing all cases of pathologically diagnosed FTD over the last 12 years. We identified and reviewed 29 cases of FTD and classified them using the most recent consensus criteria with further histological analysis of 6 initially unclassifiable cases. Detailed histological analysis of these 6 cases revealed variable numbers of ubiquitin-positive (tau and alpha-synuclein-negative) inclusions in 5 cases, consistent with the diagnosis of frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal changes (FTLD-U). As a consequence of the current re-evaluation, 18 (62%) of the 29 cases with FTD have underlying pathology consistent with FTLD-U. Therefore in our brain bank series of frontotemporal degeneration, most cases were non-tauopathies with FTLD-U accounting for 62% of all the diagnoses.

Aged↗
PubMed2001

Oncostatin M promotes biphasic tissue factor expression in smooth muscle cells: evidence for Erk-1/2 activation.

Tissue factor (TF), a transmembrane glycoprotein, initiates the extrinsic coagulation cascade. TF is known to play a major role in mediating thrombosis and thrombotic episodes associated with the progression of atherosclerosis. Macrophages at inflammatory sites, such as atherosclerotic lesions, release numerous cytokines that are capable of modulating TF expression. This study examined the role of oncostatin M (OSM), a macrophage/ T-lymphocyte-restricted cytokine, in the expression of TF in vascular smooth muscle cells (SMCs). It is reported here that OSM stimulated a biphasic and sustained pattern of TF messenger RNA (mRNA). The effect of OSM on TF mRNA expression was regulated at the transcriptional level as determined by nuclear run-offs and transient transfection of a TF promoter-reporter gene construct. OSM-induced TF expression was regulated primarily by the transcription factor NF-kappaB. Activation of NF-kappaB by OSM did not require IkappaB-alpha degradation. Inhibition of MEK activity by U0126 prevented OSM-induced TF expression by suppressing NF-kappaB DNA binding activity as determined by gel-shift analysis. Further, inhibition of Erk-1/2 protein by antisense treatment resulted in suppression of TF mRNA expression, indicating a role for Erk-1/2 in modulating NF-kappaB DNA binding activity. These studies suggest that the induced expression of TF by OSM is primarily through the activation of NF-kappaB and that activation of NF-kappaB is regulated in part by the MEK/Erk-1/2 signal transduction pathway. This study indicates that OSM may play a key role in promoting TF expression in SMCs within atherosclerotic lesions.

Blood Coagulation↗
PubMed2001

Cooperative hemoglobins: conserved fold, diverse quaternary assemblies and allosteric mechanisms.

Assembly of hemoglobin subunits into cooperative complexes produces a remarkable variety of architectures, ranging in oligomeric state from dimers to complexes containing 144 hemoglobin subunits. Diverse stereochemical mechanisms for modulating ligand affinity through intersubunit interactions have been revealed from studies of three distinct hemoglobin assemblages. This mechanistic diversity, which occurs between assemblies of subunits that have the same fold, provides insight into the range of regulatory strategies that are available to protein molecules.

Allosteric Site↗
PubMed2000

Induction of the urokinase plasminogen activator system by oncostatin M promotes endothelial migration.

Oncostatin M (OSM) is an inflammatory cytokine produced by activated macrophages and T-lymphocytes. We have previously demonstrated that OSM-induced endothelial cell migration, unlike endothelial cell proliferation and spindle formation, is independent of basic fibroblast growth factor expression (Wijelath et al. [1997] J. Cell. Sci. 110:871-879). To better understand the mechanism of OSM-induced endothelial cell migration, this study examined the potential role of the plasminogen activator system in promoting OSM mediated endothelial cell migration. OSM stimulated increased mRNA levels of urokinase-plasminogen activator (uPA) and urokinase-plasminogen activator receptor (uPAR) in a time and dose-dependent manner. Transcriptional run-off and mRNA stability analysis demonstrated that the increase in uPA and uPAR mRNA levels was due to both increased gene transcription and mRNA stability. The increase in mRNA correlated with increased protein levels of both uPA and uPAR. This increase was reflected in elevated levels of membrane-bound plasmin activity. OSM-induced endothelial cell migration was only partially dependent on plasmin activity since incubating endothelial cells without plasminogen or, in the presence of aprotinin, resulted in suppression of endothelial cell migration, indicating that OSM promoted endothelial cell migration through both a plasmin-dependent and -independent mechanism. Our results imply a role for OSM in promoting endothelial cell migration via a plasmin-dependent pathway and a uPAR-mediated pathway. Together, these and other recent studies support a role for OSM in modulating the different phases of angiogenesis.

Cells, Cultured↗
PubMed2000

Structural hierarchy in erythrocruorin, the giant respiratory assemblage of annelids.

Many annelids, including the earthworm Lumbricus terrestris, have giant cooperative respiratory proteins (molecular masses greater than 3.5 million Da) freely dissolved in the blood, rather than packaged in cells. These complexes, termed either erythrocruorins or hemoglobins, are assembled from many copies of both hemoglobin subunits and nonhemoglobin or "linker" subunits. In this paper, we present the crystal structure of Lumbricus erythrocruorin at 5.5-A resolution, which reveals a remarkable hierarchical organization of 144 oxygen-binding hemoglobin subunits and 36 nonhemoglobin linker subunits. The hemoglobin chains arrange in novel dodecameric substructures. Twelve trimeric linker complexes project triple-stranded helical coiled-coil "spokes" toward the center of the complex; interdigitation of these spokes appears crucial for stabilization. The resulting complex of linker chains forms a scaffold on which twelve hemoglobin dodecamers assemble. This structure specifies the unique, self-limited assemblage of a highly cooperative single molecule.

Animals↗
PubMed2000

Differential recognition of snake venom proteins expressing specific Arg-Gly-Asp (RGD) sequence motifs by wild-type and variant integrin alphaIIbbeta3: further evidence for distinct sites of RGD ligand recognition exhibiting negative allostery.

Several studies have demonstrated that the amino acid residues flanking the Arg-Gly-Asp (RGD) sequence of high-affinity ligands modulate their specificity of interaction with integrin complexes. Because of the absence of structural data for integrin complexes with bound ligand, the molecular basis for this specificity modulation remains obscure. In a previous paper [Rahman, Lu, Kakkar and Authi (1995) Biochem. J. 312, 223-232] we demonstrated that two genetically distinct venom-derived RGD proteins, kistrin and dendroaspin (both containing the sequence PRGDMP), were simple competitors, indicating the recognition of an identical binding site on the alpha(IIb)beta(3) complex. Furthermore, both kistrin and dendroaspin inhibited the binding of the disintegrin elegantin (containing the sequence ARGDNP) via a non-competitive mechanism, suggesting that the binding of elegantin to the alpha(IIb)beta(3) complex was at a remote site and down-regulated via an allosteric mechanism. Here we present further evidence for distinct RGD ligand recognition sites on the alpha(IIb)beta(3) complex that exhibit a negative allosteric relationship. A panel of well-characterized recombinant dendroaspin and elegantin derivatives were employed for this study. These recombinant molecules were constructed as glutathione S-transferase fusion proteins with either an Ala or Pro residue N-terminal to the RGD sequence in combination with either a Met or an Asn residue immediately C-terminal. Equilibrium competition experiments showed that elegantin binding to ADP-treated platelets was inhibited by derivatives Eleg. AM (ARGDMP) and Eleg. PM (PRGDMP) via an allosteric competitive mechanism, providing direct evidence that modulation of the RGD motif can alter competitive behaviour. In addition, recombinant kistrin and dendroaspin both inhibited elegantin binding via a non-competitive mechanism, confirming our previous observations. Further evidence for distinct binding sites employing an independent approach was obtained by analysing the binding of the panel of venom proteins to the functionally defective heterodimer alpha(IIb)beta(3) Ser(123)-->Ala expressed on Chinese hamster ovary cells. These studies demonstrated that simple competitors kistrin and dendroaspin bound with high affinity to the variant integrin complex. In contrast, the binding of elegantin and most significantly, recombinant Dendro. PN (PRGDNP) and Dendro. AN (ARGDNP) were abolished. These observations, taken together, are consistent with a model depicting the presence of distinct sites of RGD ligand recognition on the alpha(IIb)beta(3) complex that show the preferential recognition of specific RGD motifs. Competition experiments demonstrate a negative allosteric relationship between these RGD recognition sites.

Alanine↗
PubMed2000

Two distinct lineages of macaque gamma herpesviruses related to the Kaposi's sarcoma associated herpesvirus.

BACKGROUND: KSHV, Kaposi's sarcoma-associated herpesvirus, is a necessary cofactor for the development of Kaposi's sarcoma (KS). We have previously reported KSHV-related DNA sequences in retroperitoneal fibromatosis (RF) tissue from two species of macaque. The putative herpesvirus was called RFHV for RF-associated herpesvirus. These data suggested that KSHV is a human representative of a larger family of primate herpesviruses. OBJECTIVE: To identify and characterize other members of a putative family of KSHV-related herpesviruses in macaques in order to obtain information on the evolutionary history of KSHV infection in humans. STUDY DESIGN: Lymphoid tissue cells and blood leukocytes from rhesus-, cynomolgus- and pigtailed-macaques were tested for the presence of unknown herpesviruses using degenerate primer-driven PCR amplification. The sequences obtained were compared against known herpesvirus sequences. RESULTS: We have identified new herpesvirus DNA sequences in each of the three macaque species. Sequence comparisons indicate that these new viruses are most related to each other and form a separate phylogenetic lineage within the gamma herpesviruses. Screening of PBMC from Indonesian-origin quarantine animals suggests that these viruses (MGV, macaque gamma virus) are species-specific, and highly prevalent in the wild. They are readily cultured in vivo, and share a common tissue tropism with the previously identified RFHV. CONCLUSIONS: MGV and RFHV represent two independent introductions of an ancestral gamma herpesvirus into macaque precursors.

Amino Acid Sequence↗
PubMed1998

Need for job adjustment in pregnancy. Early prediction based on work history.

OBJECTIVE: To examine whether a woman's need for job adjustment in pregnancy can be predicted by a short interview on working conditions at the first prenatal visit. DESIGN: Midwives included a semi-structured work history during the interview of unselected first prenatal visits. Their early prediction about the woman's need for job adjustment was compared with the woman's own later report of such need and the need expressed as a risk score for preterm birth based on the woman's self-reported working conditions. Data on both were collected by a questionnaire presented to the woman at about the 36th week of pregnancy. SETTING: Seven maternity centres in Oslo, Norway, April 1993-March 1994. SUBJECTS: 160 pregnant women in paid work. MAIN OUTCOME MEASURES: The proportion of predictions of presence (positive predictive value) or absence (negative predictive value) of need that was confirmed by the woman's later report, or the risk score. RESULTS: The positive predictive value was 86% and the negative predictive value 50% with the woman's later report as reference, and 56 and 79%, respectively, with the risk score for preterm birth as reference. CONCLUSION: The work history allows early prediction of need for job adjustment in pregnancy.

Adult↗
PubMed1998

Work pace control and pregnancy health in a population-based sample of employed women in Norway.

OBJECTIVES: This study explored the possible effects of power to control one's own work pace on pregnancy health. METHODS: Questionnaires were sent to all parturients in Norway between 16 October and 26 November 1989 for completion prior to discharge from the hospital; 87.2% responded. The study population comprised 3321 respondents with singleton pregnancies and paid work beyond the 3rd month of pregnancy. Power to control work pace was measured as self-reported influence on breaks and work pace and absence of external pacing. Pregnancy health was defined by the prevalence of preeclampsia, disabling posterior pelvic pain, low-back pain, and birthweight of <2500 g for the offspring. RESULTS: Pregnancy health improved with increasing power to control work pace, both in manual and nonmanual work. The risk decreased with increasing control for all 4 outcomes, but the impact on birthweight was restricted to nullipara. After adjustment for age, parity, education, smoking, and manual work, the decreasing trend remained significant for preeclampsia and low birthweight of the first born. In a comparison with women with the highest level of control, the adjusted odds ratios for women with no control were 1.6 [95% confidence interval (95% CI) 0.9-3.1] for preeclampsia, 1.6 (95% CI 1.0-2.4) for disabling posterior pelvic pain, 1.3 (95% CI 1.0-1.8) for low-back pain, and 2.5 (95% CI 0.9-6.8) for low birthweight (nullipara). CONCLUSIONS: Women with power to control their own work pace had better pregnancy health than women without such power. The results suggest increased individual control over work pace as a prime target for job adjustment during pregnancy.

Adolescent↗
PubMed1998

Strenuous working conditions and birthweight, Norway 1989.

OBJECTIVE: To examine whether strenuous working conditions in pregnancy are associated with reduced birthweight. METHOD: Cross-sectional, population based study. Retrospective data collection by questionnaire to parturients in all maternity wards in Norway 16.10-26.11.89, completed before discharge from hospital, with response rate 87.2%. The study population consists of the 5388 women with singleton births, of whom 3321 were in paid work beyond the third month of pregnancy. Main outcome measures are prevalence of birthweight <2500 grams (LBW) and mean birthweight. RESULTS: Strenuous working conditions increased risk of LBW, but only for nullipara, particularly non-smoking nullipara. Odds ratios with 95% confidence intervals for non-smoking nullipara, adjusted for age, education and income, were 0.3 (0.1,0.9) for influence on work pace, 2.8 (1.2,6.5) for exposure to heavy lifting and 2.2 (0.8,5.8) for twisting/bending. Four groups of occupations were defined according to exposure, solely based on reports from mothers with non-LBW children in order to avoid recall bias. Prevalence of LBW increased from 0.8% in the least exposed to 8.3% in the most exposed group. (Test for trend: p<0.05, after adjustment for age, education and income.) Strenuous working conditions had no independent effect on mean birthweight after adjustment for age, education, income and smoking. CONCLUSION: Strenuous work increased the risk of LBW in nulliparae, particularly in non-smokers. Lack of influence on work pace was the strongest risk factor. The preventive effect of job modification in pregnancy may parallel smoking cessation.

Adult↗
PubMed1997

Working conditions and prevalence of pre-eclampsia, Norway 1989.

OBJECTIVE: To study the associations between working conditions and pre-eclampsia. METHODS: A cross-sectional study based on questionnaires to all parturients was conducted in Norway from 16 October 1989 to 26 November 1989, with an 87.2% response rate. Of the 5388 responders with singleton pregnancies, 3321 continued in paid work beyond the 3rd month of pregnancy. Pre-eclampsia was recorded if the woman reported hospitalization for hypertension, or if proteinuria and hypertension were diagnosed more than once in the pregnancy. RESULTS: The prevalence of pre-eclampsia was increased in work involving the lifting of heavy loads of 10-20 kg (adjusted odds ratio (OR), 1.8; 95% CI, 1.2-2.5), hectic work pace (OR, 1.4; 95% CI, 1.0-2.0, P < 0.05), work with hands above shoulder level (OR, 1.4; 95% CI, 1.0-2.2; P = 0.07) and for parous women, shift work (OR, 2.0; 95% CI, 1.1-3.6). It was reduced when the woman had an influence on work pace (OR, 0.7; 95% CI, 0.5-1.0; P = 0.07). Prevalence was also increased with daily consumption of more than four cups of coffee (OR, 1.6; 95% CI, 1.1-2.3). CONCLUSION: Prenatal care should include assessment of working conditions, as early improvements may reduce the risk of pre-eclampsia.

Adult↗
PubMed1997

Work load, job control and risk of leaving work by sickness certification before delivery, Norway 1989.

Sickness absence in pregnancy has been shown to be associated with strenuous working conditions and parity. So far, few studies have made adjustments for possible interaction and confounding. Such adjustments are needed to more precisely identify targets for preventive measures. We have, therefore, in a representative population of pregnant employees in Norway 1989, computed adjusted odds ratios for leaving work by sickness absence more than three (LSC > 3) and eight (LSC > 8) weeks before delivery according to working conditions identified as risk factors in earlier studies; adjusted for job control, domestic conditions and sickness absence the year prior to pregnancy. The cumulative percentage of LSC > 8 and LSC > 3 was 26.4 and 51.1. Ergonomically strenuous postures and heavy lifting increased the risk of both outcomes. In addition, shift work and hectic work pace increased the risk of LSC > 3. Influence on breaks reduced risk. Only para experienced reduced risk of LSC when working part-time. Sicklisting the year prior to pregnancy had no confounding effect, which suggest that pregnancy represents a new incompatibility with work. Preventive measures should address work postures and heavy lifting, as well as conditions influencing the woman's control with her time.

Adult↗
PubMed1997

Job adjustment as a means to reduce sickness absence during pregnancy.

OBJECTIVES: This study examined the effect of job adjustment on sickness absence during pregnancy and also determined the conditions under which such adjustments are obtained. METHODS: Data were derived from a nationally representative survey on work conditions during pregnancy in Norway in 1989. For employees (N = 2713) remaining in the same job throughout pregnancy, the percentage of women on sick leave immediately before delivery was determined according to the need for job adjustment and the obtainment of job adjustment. Those obtaining job adjustment were grouped according to workplace size, labor-market sector, co-worker gender, educational level, work schedules, weekly workhours, children under 16 years of age in the household, and age. RESULTS: All told, 1691 women (62.3%) needed job adjustment, among whom 936 (55.4%) obtained such adjustment. The proportions of those on sick leave before delivery were 45.2% for "no need", 67.9% for "need - adjustment obtained", and 79.2% for "need - adjustment not obtained". In the last category, the difference (versus "adjustment obtained") constituted 44.5% of the weeks lost because of sickness absence in the last half of pregnancy. The odds ratio (OR) for obtaining job adjustment was larger for workplaces with more than 50 employees (OR 1.4) and smaller for jobs with work schedules other than daytime or shift work (OR 0.5) and also for women living with children under 16 years of age (OR 0.8). CONCLUSIONS: Job adjustment is associated with reduced sickness absence during pregnancy. Further studies should explore workplace characteristics that make it difficult to obtain such adjustments, as required by law.

Absenteeism↗
PubMed1996

Fertility patterns according to occupational grouping in Norway, 1989.

In the early 1990s, most pregnant women in Norway were in gainful employment. This led to increased interest in the possible consequences for reproductive health, and a growing concern for the need to accommodate the pregnancy. We have therefore investigated how accurately general fertility rates predict the number of pregnancies in the workforce. Fertility rates (FR) among employed women and standardized fertility ratios (SFR) in occupational groups were estimated on the basis of information from the Labour Market Statistics and the national survey "Pregnancy and Work", Norway, 1989. The fertility rate among employed women was 17% higher than the general fertility rate. Two occupational groups had significantly different SFRs: technical/professional workers (SFR 118) and transport/communication workers (SFR 82). In addition, differences were found for parity-specific SFRs in administrative/executive work (SFR nullipara 80, SFR para 125) and service work (SFR nullipara 114, SFR para 80). We suggest that work status and occupation should be included among the variables registered in the Medical Birth Registry of Norway, in order to facilitate routine presentations of fertility rates and pregnancy outcomes for women in paid work. The results further indicate that work-specific conditions influence first-birth fertility. This should be explored in demographic studies of the relation between women's fertility and participation in paid work.

Adolescent↗
PubMed1996

Smoking in pregnancy: a way to cope with excessive workload?

OBJECTIVE: To examine if abstention from smoking in pregnancy increases with opportunities to limit workload. DESIGN: Cross-sectional study based on self-administered questionnaires to women post partum. SETTING: All maternity wards in Norway, 16 October-26 November 1989. SUBJECTS: 5 438 women, or 87.2% of all parturients in Norway during the study period. MAIN OUTCOME MEASURE: The abstention fraction (AF) defined as percentage of nonsmokers in pregnancy among prepregnancy daily smokers. RESULTS: The abstention fraction was lower for women with lack of influence on work pace, with hectic work pace, exhaustion after work or work schedules other than daytime, for women with children <16 years of age in the household, and for women in paid work with 20 hours or more of housework weekly, than for women without these conditions. Adjusted odds ratios (OR) for abstention were low for women with children <16 years both when in paid work (OR 0.4) and as housewives (OR 0.3). Women who received extra help with housework had a high abstention fraction (OR 1.6) both when in paid work and as housewives. The abstention fraction was high for women with daytime work (OR 1.5) and low with hectic work pace (OR 0.7), compared with women without these conditions. CONCLUSION: Abstention from smoking in pregnancy increases with opportunities to limit total workload.

Adaptation, Psychological↗
PubMed1994

Psychiatric nursing in a psychosocial setting.

The revolutionary upheaval in this nation's health care system may cause many psychiatric nurses in traditional settings to be concerned about their future role. According to the United States Department of Health and Human Services (1990), there were 66,142 psychiatric registered nurses employed in inpatient hospital settings as of 1988. The advent of managed care, decrease in entitlements, and overburdening of the health care system has again led to less accessibility to inpatient psychiatric hospitalization, and briefer stays once hospitalized. As treatment once again moves into the community, nurses may wonder what types of new programs will follow, and if they will employ psychiatric nurses. One type of community based program uses the principles of psychosocial rehabilitation. The Village Integrated Services Agency is such an organization, allowing nurses to fully use their nursing skills, but without the focus on illness and the constraints on autonomy typically experienced in hospital settings.

Activities of Daily Living↗