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Biomedical subjects

K Hansen

Publications and source records attributed to K Hansen.

At least 73 records · Page 4Linked to original sources

Methodologic aspects of acetylcholine-evoked relaxation of rabbit aorta.

The acetylcholine-evoked relaxation of rabbit isolated thoracic aorta precontracted by phenylephrine was studied. Phenylephrine caused a steady contraction that was maintained for 6 h. In the presence of calcium disodium ethylenediaminetetraacetate (EDTA) and ascorbic acid the contraction decreased with time. N(G)-Nitro-L-arginine abolished the inhibitory effect of EDTA and ascorbic acid. Acetylcholine evoked a rapid concentration-dependent relaxation that recovered spontaneously and slowly, but fully, with time. Relaxation evoked by equieffective concentrations of carbachol and acetylcholine had the same time course. Cumulative addition of acetylcholine (10(-7)-3 x 10(-5) M) caused a marked relaxation that was reverted slightly at high concentrations. The relaxation was the same with rings derived from the upper, middle, and lower part of the thoracic aorta. Two consecutive concentration-response curves for acetylcholine obtained at a 2-h interval demonstrated a slight development of tachyphylaxis. The relaxation was inversely related to precontractile tension evoked by phenylephrine when expressed as a percentage, but independent when expressed as g tension. Storage of aorta in cold salt solution for 24 h did not alter the relaxation. EDTA and ascorbic acid did not alter the relaxation. It is concluded that (1) EDTA and ascorbic acid can not be used with impunity to stabilize catecholamines used as preconstriction agents; (2) the reversal of the acetylcholine-evoked relaxation is not due to hydrolysis of acetylcholine; (3) the relaxation is uniform in all segments of thoracic aorta; (4) cold storage of aorta does not alter the relaxation; and (5) acetylcholine releases the same amount of relaxing factor, irrespective of the precontractile tension.

Acetylcholine↗

Risk factors for lack of recovery of ADL independence after hospital discharge.

OBJECTIVE: To determine risk factors for lack of recovery of independent functioning after hospitalization for acute medical illness. DESIGN: Secondary analysis of cohort study of patients receiving home nursing after discharge. SETTING: Evaluations performed in the home after discharge and 1 month later. PARTICIPANTS: A total of 73 adults aged 65 years and older who were independent in activities of daily living (ADLs) before hospitalization and dependent at discharge. MEASUREMENTS: Self-report and objective measures of function, mobility, and cognition. OUTCOME: Return to independence in ADLs 1 month after discharge. RESULTS: Fifty-nine percent of patients did not return to previous ADL independence by 1 month postdischarge. The likelihood for not recovering was 87% (95% CI, 70-100%) if a patient had a Mini-Mental State Examination score (MMSE) < 24 at discharge (P = .015). Among patients with good cognition, 85% (95% CI, 66-100%) of those who used an assistive device indoors before hospitalization did not recover (P = .007). Among patients with good cognition and no previous assistive device use, 73% (95% CI, 47-99%) of those with a Timed "Up and Go" of > or = 40 seconds did not recover (P = .012). The likelihood of recovery was high (76%, 95% CI 56-96%) if a patient had no assistive device prehospital, a good MMSE, and a Timed "Up and Go" of < 20 seconds. CONCLUSION: We hypothesize that a classification strategy using cognition, prehospital mobility, and discharge physical performance will predict patients who are less likely to recover functional independence after hospitalization. If this is validated in future study, it may help clinicians identify patients who are more likely to benefit from additional intervention.

Activities of Daily Living↗

Flavin-containing monooxygenase-mediated N-oxidation of the M(1)-muscarinic agonist xanomeline.

The involvement of flavin-containing monooxygenases (FMOs) in the formation of xanomeline N-oxide was examined in various human and rat tissues. Expressed FMOs formed xanomeline N-oxide at a significantly greater rate than did expressed cytochromes P-450. Consistent with the involvement of FMO in the formation of xanomeline N-oxide in human liver, human kidney, rat liver, and rat kidney microsomes, this biotransformation was sensitive to heat treatment, increased at pH 8.3, and inhibited by methimazole. The latter two characteristics were effected to a lesser extent in human kidney, rat liver, and rat kidney microsomes than were observed in human liver microsomes, suggesting the involvement of a different FMO family member in this reaction in these tissues. As additional proof of the involvement of FMO in the formation of xanomeline N-oxide, the formation of this metabolite by a characterized human liver microsomal bank correlated with FMO activity. The FMO forming xanomeline N-oxide by human kidney microsomes exhibited a 20-fold lower K(M) (average K(M) = 5.5 microM) than that observed by the FMO present in human liver microsomes (average K(M) of 107 microM). The involvement of an FMO in the formation of xanomeline N-oxide in rat lung could not be unequivocally demonstrated. These data and those in the literature suggest that the increased prevalence of N-oxidized metabolites of xanomeline after s.c. dosing as compared with oral dosing may be due to differences in the affinity of various FMO family members for xanomeline or to differences in exposure to xanomeline that these enzymes receive under different dosing regimens.

Animals↗

New aspects of chemoreception in flies.

For studies of insect taste the sensory cells of labellar taste hairs on the proboscis of calliphorid flies (e.g., Phormia) are preferred objects. Three sensory cells are electrophysiologically characterized: a sugar cell, a water cell and a cation or salt cell. Studying hairs on legs and proboscis of other families of flies we recently obtained results that extend our knowledge about the complexity of food detection in flies. The hoverfly Eristalis tenax (Syrphidae family) feeds on nectar and pollen of flowers. While nectar is recognized via the sugar cell, the so-called salt cell is activated by low concentrations of a water-soluble substance in extracts of pollen. From several tested pollen constituents only proline, an essential amino acid for pollen germination, stimulates the salt cell. The discrimination between salt and pollen in behavioral tests can be explained by the finding that the water cell remains active in the presence of pollen extract, but is inhibited by salts. Obviously the water cell activity is involved in the feeding decision. We already described a similar situation in Phormia, where the salt cell activity only elicits feeding behavior when the water cell is active too. In contrast to the sugar cells of species of flies studied so far the sugar cell of the house fly Musca domestica (Muscidae family) is highly sensitive to lactose, a disaccharide (beta-galactoside (1-->4) glucoside) naturally occurring only in the milk of mammals. Thus sugar spectra adapt to special environmental food situations. The fifth tarsomere of the forelegs of Musca bears besides two D-hairs 46 hairs of the B-type. The B-hairs are functionally not uniform in contrast to their structural identity. Only two hairs, the 'water hairs,' contain a water cell beside a spontaneously firing cell, but no sugar cell. Other examples of diversity are hairs that contain apart from the classical sugar cells, additional cells which react either to p-nitrophenyl-beta-galactoside, but not to the chemically related lactose, or to p-nitrophenyl-alpha-glucoside. Therefore the rule established for the labellar taste hairs that each hair type contains the same physiological equipment of sensory cells, does not hold for the taste hairs of the legs.

Animals↗

Nascent transcription from the nmt1 and nmt2 genes of Schizosaccharomyces pombe overlaps neighbouring genes.

We have determined the extent of the primary transcription unit for the two highly expressed genes nmt1 and nmt2 of Schizosaccharomyces pombe. Transcription run-on analysis in permeabilized yeast cells was employed to map polymerase density across the 3'-flanking region of these two genes. Surprisingly, polymerases were detected 4.3 kb beyond the nmt1 polyadenylation [poly(A)] site and 2.4 kb beyond the nmt2 poly(A) site, which in each case have transcribed through an entire convergent downstream transcription unit. However, the steady-state levels of both downstream genes were unaffected by the high level of nmt1 or nmt2 nascent transcription. Analysis of nmt1 and nmt2 RNA 3' end formation signals indicates that efficient termination of transcription requires not only a poly(A) signal but also additional pause elements. The absence of such pause elements close to the poly(A) sites of these genes may account for their extended nascent transcripts.

Base Sequence↗

Metastasis-associated Mts1 (S100A4) protein modulates protein kinase C phosphorylation of the heavy chain of nonmuscle myosin.

Mts1 protein (S100A4 according to a new classification) has been implicated in the formation of the metastatic phenotype via regulation of cell motility and invasiveness. Previously we have demonstrated that Mts1 protein interacted with the heavy chain of nonmuscle myosin in a calcium-dependent manner. To elucidate the role of the Mts1-myosin interaction, we mapped the Mts1-binding region on the myosin heavy chain molecule. We prepared proteolytically digested platelet myosin and a series of overlapped myosin heavy chain protein fragments and used them in a blot overlay with Mts1 protein. Here we report that the Mts1-binding site is located within a 29-amino acid region, at the C-terminal end of the myosin heavy chain (between 1909-1937 amino acids). Two-dimensional phosphopeptide analysis showed that Mts1 protein inhibits protein kinase C phosphorylation of the platelet myosin heavy chain at Ser-1917. We hypothesize that Mts1 protein regulates cytoskeletal dynamics of the metastatic cells through modulation of the myosin phosphorylation by protein kinase C in calcium-dependent fashion.

Binding Sites↗

Does orthodontic proclination of lower incisors in children and adolescents cause gingival recession?

In this investigation we sought to assess the effect of orthodontic proclination of lower incisors in children and adolescents with respect to the possible development of gingival recession. Ninety-eight children with a mean +/- SD start-of-treatment age of 12.8 +/- 1.4 years, treated with the Herbst appliance, were surveyed, for a total of 392 lower incisors. Lateral head films, dental casts and intraoral photographs were analyzed with respect to the degree of orthodontic proclination, crown height, and gingival recession. In all subjects, Herbst treatment resulted in varying degrees of lower-incisor proclination (mean = 8.9 degrees, range = 0.5 degrees to 19.5 degrees). In 380 of the surveyed teeth (97%), either no recession developed or preexisting recession remained unchanged during Herbst therapy. In only 12 teeth (3%) did recession develop or preexisting recession deteriorate during treatment. No interrelation was found between the amount of incisor proclination and the development of gingival recession. In conclusion, orthodontic proclination of lower incisors in children and adolescents seems not to result in gingival recession.

Adolescent↗

Human carcinoma-associated antigen (HCA), isolated from the endometrial carcinoma cell line KLE-1 and ascitic fluid of a patient with ovarian carcinoma; comparison with epiglycanin.

Human carcinoma-associated antigen (HCA), detected by the mouse monoclonal anti-epiglycanin antibody, AE-3, has been isolated from ascitic fluid taken from a patient with metastatic ovarian adenocarcinoma and from spent medium of the human endometrial carcinoma cell line KLE-1 and compared with epiglycanin. The ascitic fluid and the spent medium were concentrated by a Filtron Ultrasette 100 K Omega membrane and fractionated by gel filtration on Sepharose CL-2B. The active fractions which consisted mainly of glycoproteins having relative molecular weights in the range 1000-2000 kDa compared to dextrans, were further purified by affinity chromatography on a column of immobilized AE-3. The active fraction was subjected to SDS-PAGE and blotted onto a PVDF membrane. The amino acid composition of HCA isolated from the two sources, were related but not identical and both showed some differences from the amino acid composition of epiglycanin. They all have, however, compositions typical of mucin-type glycoproteins. The isoelectric point for HCA from both KLE-1 and ascitic fluid were determined to be at pH 1.8 and the buoyant densities were about 1.4 g/ml as determined by cesium trifluoroacetate gradient centrifugation.

Aged↗

Analysis of low-dose digital lateral cephalometric radiographs.

OBJECTIVE: To examine the effects of the dose reduction obtained with photostimulable phosphor computed radiography (CR) on the identification of cephalometric landmarks. METHODS: Dose reductions of 50% and 75% respectively were obtained by placing three storage phosphor image plates in the same cassette. Lateral cephalograms were exposed on ten patients. Seven observers identified 14 anatomical landmarks on the images. RESULTS: The location of anatomical landmarks on the lateral cephalograms was not effected by the decreased dose (P > 0.05). Interobserver variation was the major influence. CONCLUSION: A dose reduction of 75% does not effect the localization of anatomical landmarks in lateral cephalograms obtained with CR.

Adolescent↗

Immunoserologic evidence of Human Granulocytic Ehrlichiosis in Danish patients with Lyme neuroborreliosis.

Human Granulocytic Ehrlichiosis (HGE) is a recently described human illness in the US which manifests as fever, myalgia and headache combined with pancytopenia and elevated concentrations of hepatic transaminases. Genetic analyses indicate that the agent of HGE appears to be an Ehrlichia species that is closely related to E. equi and E. phagocytophila. Ixodes dammini and I. scapularis were identified as potential vectors of HGE. Ixodes ticks are also the vector of Borrelia burgdorferi, the agent of Lyme borreliosis. The presence of antibodies against Ehrlichia in 132 sera from Danish patients with definite Lyme neuroborreliosis were examined in order to provide immunoserologic evidence of this infection in Denmark. Patients with Lyme neuroborreliosis were chosen as a test cohort, as these patients had been infested by a tick sufficient for transmission of B. burgdorferi. All had cerebrospinal fluid lymphocytic pleocytosis. As controls, serum samples from 50 healthy Danish blood donors were included. Of the 132 patients with Lyme neuroborreliosis, 5 (3.8%) reacted with the E. equi antigen substrate at titres 1:128. None of the blood donors were found seropositive for E. equi. At least 2 of the patients found seropositive for HGE constituted probable cases of HGE with E. equi antibody titres of at least 80 combined with fever, headache and myalgias. However, in no cases were we able to detect the presence of the HGE agent in the serum by PCR. We conclude that human exposure to granulocytic Ehrlichiae species may also occur in Europe, although further studies will be necessary to document active infection with these potential pathogens.

Adult↗

The cost of home-based care for HIV/AIDS patients in Zimbabwe.

From a study on the cost and quality of community home-based care (CHBC) for HIV/AIDS patients in Zimbabwe, programme and household costs were estimated. Interviews, using a structured questionnaire, were held with 60 patients and caregivers sampled from six types of established CHBC schemes. Detailed cost information was collected from four home care programmes, two urban and two rural. The cost of a home visit in the two urban programmes studied was estimated to be Z$129 (US$16) in one, and Z$183 (US$23) in the other. In one of the two rural schemes, the cost of a home visit was Z$313 (US$38), in the other this was Z$343 (US$42). A large proportion of these costs were not of direct benefit to the patients, as approximately 56-75% of the total cost per home visit was spent getting to the patient. The costs of a home visit in a rural home-based care programme corresponded to the costs of 2.7 inpatient days in a district hospital. The family cost of caring for a bedridden AIDS patient over a three-month period was estimated to be between Z$556-841. Caregivers spent as much as 2.5-3.5 hours a day on routine patient care. The programme costs are high, and schemes do not generally assess effectiveness, nor cost-effectiveness. The high cost of home visits leads to less frequent visits, leaving a larger part of both the burden and the cost of care to the families and the patients.

Cost of Illness↗

Sepsis evaluations in hospitalized infants with bronchiolitis.

OBJECTIVES: To define variation in the decision to perform a sepsis evaluation in hospitalized infants with bronchiolitis, to define predictors of the decision and to measure the clinical and cost outcomes. METHODS: Retrospective chart review of all nonintensive care unit infants < or = 60 days with any discharge diagnosis of bronchiolitis (n = 282 from 1993 to 1995 in a 232-bed pediatric hospital. Process variables included temperature at sepsis work-up or Tmax if no sepsis workup. Outcome variables were charges, length of stay, sepsis workup and serious bacterial infection. RESULTS: There was no difference in mean temperature between groups with or without sepsis evaluation (38.1 degrees C, P = 0.75). Of 282 infants 140 had a sepsis workup; 5 (1.8%) had serious bacterial infection. Infants with sepsis workup had an average total charge of $4507 and length of stay of 3.4 days compared with $2998 and 2.8 days for those without (P = 0.0001 and P = 0.002, respectively). A multivariate logistic regression model was constructed with sepsis workup as the dichotomous dependent variable. Significant (P < or = 0.05) predictor variables with a positive coefficient were: higher bronchiolitis score and normal chest roentgenogram. Significant variables with a negative coefficient were: admission diagnosis of bronchiolitis, chest roentgenogram typical for bronchiolitis and age > 28 days. CONCLUSIONS: Temperature was not a predictor of sepsis evaluation. Infants with respiratory distress and normal chest roentgenogram were more likely to receive sepsis evaluations; those with recognized typical bronchiolitis and those > 28 days of age were less likely. Risk of serious bacterial infection is low; the costs of a sepsis evaluation outweigh the benefits in infants with obvious bronchiolitis.

Bronchiolitis↗

The dominant epitope of Borrelia garinii outer surface protein C recognized by sera from patients with neuroborreliosis has a surface-exposed conserved structural motif.

Epitope mapping of outer surface protein C (OspC) by using sera from patients with neuroborreliosis led to the identification of one single major immunodominant epitope within the C-terminal 10 amino acid residues. Peptide binding studies and alanine replacement scanning of the C-terminal decapeptide, PVVAESPKKP, revealed a critical role for the PKKP sequence and its terminal carboxyl group for the binding of immunoglobulin M (IgM) antibodies from patients with Lyme borreliosis. Electron microscopy of antibody-labeled spirochetes indicated that the C-terminal region is exposed on the surface of the spirochete. Based on homology to proteins of known function, this region most probably adopts a polyproline II-like helix, which is found in surface-exposed structures involved in protein-protein interactions. This structural motif is highly conserved in Borrelia species causing Lyme borreliosis and subjected to purifying selection. We suggest that the abundance of the C-terminal region of OspC on the surface of B. burgdorferi allows a multimeric high-avidity interaction between the spirochete and surface Igs on B cells. The resulting cross-linking of surface Igs on B cells may induce a T-cell-independent B-cell activation without IgM-to-IgG switching, thus explaining the lack of IgG antibodies to OspC in neuroborreliosis.

Adolescent↗

Peptide-based OspC enzyme-linked immunosorbent assay for serodiagnosis of Lyme borreliosis.

Sera from 210 patients with Lyme borreliosis (LB) were studied by an enzyme-linked immunosorbent assay (ELISA) based on a synthetic peptide (pepC10) comprising the C-terminal 10-amino-acid residues of OspC of Borrelia burgdorferi. We found that 36.3 and 45.0% of the serum samples from patients with erythema migrans (EM) and neuroborreliosis (NB), respectively, displayed immunoglobulin M (IgM) anti-pepC10 reactivities, while these samples rarely (</=8%) displayed IgG antibody reactivities. Sera from patients with acrodermatitis chronica atrophicans did not contain anti-pepC10 antibodies. The diagnostic performance of this newly developed peptide ELISA was compared with those of an ELISA based on the full-length recombinant OspC protein (rOspC) and a commercially available ELISA based on the B. burgdorferi flagellum (Fla). The sensitivity of the IgM pepC10 ELISA was slightly lower (P < 0.04) than that of the rOspC ELISA for EM patients (36.3 versus 43.8%), while there was no difference for NB patients (45.0 versus 48.0%). However, the optical density values obtained by the pepC10 ELISA were generally higher than those obtained by the rOspC ELISA, leading to a significantly better quantitative discrimination between seropositive patients with NB and controls (P < 0.008). The specificity of the pepC10 ELISA was similar to those of the rOspC ELISA and the Fla ELISA for relevant controls including patients with syphilis and mononucleosis. Although the overall diagnostic sensitivity of the Fla ELISA was superior, 8.8 and 12.0% of the EM and NB patients, respectively, were antibody positive only by the pepC10 ELISA. Thus, use of a diagnostic test for LB based on the detection of IgM antibodies to pepC10 and Fla has increased sensitivity for the diagnosis of early LB.

Adolescent↗

Acute effects of recombinant human interleukin-6 on endocrine and central nervous sleep functions in healthy men.

Interleukin-6 (IL-6) is a proinflammatory cytokine that has been shown to mediate, in addition to immune reactions, various endocrine and central nervous components of the acute phase response. In this context, the present study aimed to specify the contributions of IL-6 to the regulation of pituitary-adrenal secretory activity and GH and TSH secretion, as well as to the regulation of central nervous sleep and mood in healthy men. Effects of a low dose of IL-6 (0.5 microgram/kg body weight) were assessed, inducing plasma IL-6 concentrations closely comparable with those typically observed after infectious challenge. Each of the 16 male subjects participated in two 14-h sessions (between 1800 and 0800 h), receiving either placebo or human recombinant IL-6 sc at 1900 h. Blood was collected repeatedly to determine plasma hormone levels, serum concentrations of cytokines, and C-reactive protein. Moreover, mood was assessed, and sleep recordings were obtained between 2300 and 0700 h. The cytokine induced a prolonged increased in plasma concentrations of ACTH and cortisol (P < 0.001), but led to a decrease in TSH concentrations (P < 0.01). In response to IL-6, subjects reported fatigue and felt more inactive and less capable of concentrating than after placebo. Sleep architecture was altered significantly by the cytokine. Slow-wave sleep was decreased during the first half and increased during the second half of sleep. Rapid eye movement sleep during the entire nocturnal sleep time was significantly decreased. After IL-6, body temperature rose slightly. C-reactive protein concentrations were dramatically increased 12.5 h after substance administration (P < 0.001). IL-6 did not affect serum concentrations of IL-2, IL-8, interferon-alpha, and interferon-gamma. The results underscore the importance of IL-6 in the cascade of cytokines for the neuroendocrine response during the acute phase reaction. In addition, IL-6 appears to be involved in changes of sleep and behavior accompanying infection and inflammatory disorders.

Adrenal Glands↗

Job demands, muscle activity and musculoskeletal symptoms in relation to work with the computer mouse.

OBJECTIVES: This study assessed work postures, movements, psychosocial job demands, and shoulder and wrist extensor muscle activity and registered the prevalence of musculoskeletal symptoms of computer-aided design (CAD) operators. METHODS: A questionnaire survey was used to study the use of the computer mouse, psychosocial work factors, and musculoskeletal symptoms among 149 CAD operators. A workplace study was performed using observations, electrogoniometers on the wrists, and electromyography to measure exposures and physiological responses during CAD work among a subgroup of the CAD operators. RESULTS: Musculoskeletal symptoms were far more prevalent for the arm or hand operating the mouse than for the other arm or hand, and women were more affected than men. The symptoms may be related to such risk factors as repetitive movements, static postures (eg, ulnar-deviated and extended wrist on the mouse side), and static muscular activation patterns. The risk factors were present due to continuous mouse use and possibly also due to high demands for mental attentiveness, precision, and information processing. CONCLUSIONS: Exposure during work with a computer mouse may present a risk for developing musculoskeletal symptoms. Improvements should focus on introducing more variation.

Adult↗

Interference of sugars with the binding of biotin to streptavidin and avidin.

Streptavidin and avidin have found widespread use as detection reagents in immunology, biochemistry and cell biology due to their high affinity binding to biotin, but the cellular functions of these proteins are not known. We have found that various sugars interfere with the binding of streptavidin and avidin to biotin. Mannose was most effective in inhibiting the binding to biotin followed by other saccharides. The inhibitory effect is most probably due to interactions of the sugars with residues in the binding pocket of streptavidin and avidin for biotin. These results show that great caution has to be exercised in the evaluation of experiments conducted with these detection reagents in the presence of sugars.

Avidin↗