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Biomedical subjects

A Hansen

Publications and source records attributed to A Hansen.

At least 127 records · Page 7Linked to original sources

Pit viper bites: rational management in locales in which copperheads and cottonmouths predominate.

The management of pitviper bites remains controversial. In order to better assess the efficacy of different treatment modalities, charts of 107 patients hospitalized for pitviper bites at University of North Carolina Hospitals between 1952 and 1992 were retrospectively reviewed. The series included 68 copperhead bites (64%), 8 cottonmouth bites (7%), 3 rattlesnake bites (3%), and 28 bites (26%) in which the snake could not be identified. First aid measures taken prior to hospitalization included cryotherapy (21%), incision and suction (22%), tight or loose tourniquets (32%), and moist heat (2%). After hospitalization, 29 patients (27%) underwent wound excision and 4 patients (4%) required fasciotomy. Antivenin was administered to 34 patients (32%) and 9 patients (26%) developed serum sickness. No patients died as a result of a bite injury and 84 patients (79%) recovered uneventfully. Complications of the injuries included coagulopathies (4%), infections (13%), tissue loss (12%), and permanent physical deformities (8%). No first aid measure significantly affected the outcome, although there was a trend toward increased complication rates in bites with moderate (grade II) or greater envenomation if cryotherapy or tourniquets were utilized. Wound excision after hospitalization was associated with a decreased complication rate in these significantly envenomated bites. Antivenin utilization did not improve outcome and there was a significantly higher incidence of tissue loss associated with its use. Therefore, no first aid measures are recommended for pitviper bites due to copperheads and cottonmouths except immobilization and elevation. Excision is efficacious for patients seen within 1 to 2 hours of bite injury. The risk of complications and questionable efficacy of antivenin outweigh any potential benefit for these patients. Data from the current series were insufficient to make definitive recommendations regarding rattlesnake bites.

Animals↗

Relaxin is not related to symptom-giving pelvic girdle relaxation in pregnant women.

BACKGROUND: The pregnancy associated hormone relaxin induces loosening of the pelvic ligaments in several species. This study was undertaken to evaluate whether pregnant women with symptom-giving girdle relaxation had increased serum relaxin concentrations during pregnancy. METHOD: Serum relaxin concentrations were measured in 38 pregnant women with symptom-giving pelvic girdle relaxation at the time of diagnosis, in the 30th and 38th week of pregnancy as well as 2 and 6 months after delivery. Fourteen pregnant women without symptoms served as a control group. Relaxin concentrations were measured by a homologous enzyme linked immuno-sorbent assay. All participants were clinically examined including tests for symptom-giving pelvic girdle relaxation. RESULTS: No differences in serum relaxin concentrations were found throughout pregnancy and after delivery. CONCLUSION: The present results do not suggest an important role for relaxin in symptom-giving pelvic girdle relaxation during human pregnancy.

Chronic Disease↗

Steroid UDP glucuronosyltransferases: characterization and regulation.

Under normal physiological conditions, glucuronidation generally terminates the biological activities of steroids and leads to their elimination in the bile and urine. This process is postulated to play a role in homeostasis by regulating the intracellular steady-state levels of these effector ligands. Indeed, the duration of response to specific steroid signals may be partly determined by the capacity of the cell or tissue to eliminate the steroids as unreactive glucuronides. Under pathophysiological conditions or during steroid therapies, glucuronidation may sometimes result in the formation of more biologically active or toxic metabolites as exemplified by the steroid D ring glucuronides. The degree of toxicity or biological effect in the cell exposed to these steroids will also depend on its complement of UGTs. To investigate these processes in more detail, the steroid specificities and distribution of individual UGTs in various target organs require elucidation. In this review, our current knowledge of the steroid specificities of various rat and human UGTs is described and preliminary investigations on the mechanisms governing tissue specificity are presented.

Animals↗

Glucose tolerance in patients with cystic fibrosis: five year prospective study.

OBJECTIVES: To study prevalence and incidence of diabetes mellitus in patients with cystic fibrosis. DESIGN: Five year prospective study with annual oral glucose tolerance tests. SETTING: CF Center Copenhagen, Denmark. SUBJECTS: 191 patients with cystic fibrosis aged above 2 years. MAIN OUTCOME MEASURES: Glucose tolerance, plasma glucose concentrations after fasting and after glucose loading, and haemoglobin A1c levels. RESULTS: Prevalence of diabetes increased from 11% (n = 21) to 24% (n = 46) during study, with annual age dependent incidence of 4-9%. Diabetes was diagnosed at median age of 21 (range 3-40). At diagnosis of diabetes, symptoms of hyperglycaemia were present in 33% of patients, fasting hyperglycaemia (> or = 7.8 mmol/l) was seen in 16%, and increased haemoglobin A1c levels (> 6.4%) were seen in 16%. Impaired glucose tolerance implied higher risk for development of diabetes than normal glucose tolerance (odds ratio 5.6). In 58% of cases with impaired glucose tolerance, however, glucose tolerance was normal at next annual test. Normal glucose tolerance was found in only 37% of patients at all five tests. Within this group of patients, median plasma glucose concentrations after fasting and after glucose loading and haemoglobin A1c levels increased by 6-8% during study. CONCLUSIONS: Prevalence and incidence of diabetes in cystic fibrosis patients was high and increased with age. Since hyperglycaemic symptoms, fasting hyperglycaemia, and increased levels of glycated haemoglobin did not reliably identify diabetes mellitus, we recommend annual oral glucose tolerance tests in all cystic fibrosis patients aged over 10 years.

Adolescent↗

Glucose transporter function is controlled by transporter oligomeric structure. A single, intramolecular disulfide promotes GLUT1 tetramerization.

The human erythrocyte glucose transporter is an allosteric complex of four GLUT1 proteins whose structure and substrate binding properties are stabilized by reductant-sensitive, noncovalent subunit interactions [Hebert, D. N., & Carruthers, A. (1992) J. Biol. Chem. 267, 23829-23838]. In the present study, we use biochemical and molecular approaches to isolate specific determinants of transporter oligomeric structure and transport function. When unfolded in denaturant, each subunit (GLUT1 protein) of the transporter complex exposes two sulfhydryl groups. Four additional thiol groups are accessible following subunit exposure to reductant. Assays of subunit disulfide bridge content suggest that two inaccessible sulfhydryl groups form an internal disulfide bridge. Differential alkylation/peptide mapping/N-terminal sequence analyses show that a GLUT1 carboxyl-terminal peptide (residues 232-492) contains three inaccessible sulfhydryl groups and that an N-terminal GLUT1 peptide (residues 147-261/299) contains two accessible thiols. The carboxyl-terminal peptide most likely contains the intramolecular disulfide bridge since neither its yield nor its electrophoretic mobility is altered by addition of reductant. Each GLUT1 cysteine was changed to serine by oligonucleotide-directed, in vitro mutagenesis. The resulting transport proteins were expressed in CHO cells and screened by immunofluorescence microscopy for their ability to expose tetrameric GLUT1-specific epitopes. Serine substitution at cysteine residues 133, 201, 207, and 429 does not inhibit exposure of tetrameric GLUT1-specific epitopes. Serine substitution at cysteines 347 or 421 prevents exposure of tetrameric GLUT1-specific epitopes. Hydrodynamic analysis of GLUT1/GLUT4 chimeras expressed in and subsequently solubilized from CHO cells indicates that GLUT1 residues 1-199 promote chimera dimerization and permit GLUT1/chimera heterotetramerization. This GLUT1 N-terminal domain is insufficient for chimera tetramerization which additionally requires GLUT1 residues 200-463. Extracellular reductants (dithiothreitol, beta-mercaptoethanol, or glutathione) reduce erythrocyte 3-O-methylglucose uptake by up to 15-fold. This noncompetitive inhibition of sugar uptake is reversed by the cell-impermeant, oxidized glutathione. Reductant is without effect on sugar exit from erythrocytes. Dithiothreitol doubles the cytochalasin B binding capacity of erythrocyte-resident glucose transporter, abolishes allosteric interactions between substrate binding sites on adjacent subunits, and occludes tetrameric GLUT1-specific GLUT1 epitopes in situ. CHO cell-resident GLUT1 structure and transport function are similarly affected by extracellular reductant. We conclude that each subunit of the glucose transporter contains an extracellular disulfide bridge (Cys347 and Cys421) that stabilizes transporter oligomeric structure and thereby accelerates transport function.

3-O-Methylglucose↗

[Different use of thrombolytic therapy in men and women with acute myocardial infarction].

Previous studies have reported a difference between the use of invasive therapeutic procedures in men and women with coronary artery disease. The aim of this study was to evaluate if this difference also exists in the initial treatment of acute myocardial infarction and for numbers of non-invasive procedures performed. We examined 448 patients (283 men and 165 women). We found a significant gender difference concerning the numbers treated with streptokinase, namely 47.3% of the men compared to 33.3% of the women. The delay from onset of symptoms until admission was nearly the same for both sexes. There was, however, a considerably longer in-hospital delay before start of treatment for the women compared to the men. The time-difference was significant for patients below 70 years of age. We found no gender difference in the numbers of performed exercise-tests and echocardiographic examinations. There was a slightly non-significant higher mortality among the women. We also calculated the numbers of patients without contraindications to treatment with streptokinase who were not treated, here we found no difference between the sexes. We conclude that women with symptoms suggesting acute myocardial infarction should be carefully evaluated immediately after admission to hospital to improve thrombolytic therapy.

Aged↗

Glycosylation analysis of a polyreactive human monoclonal IgG antibody derived from a human-mouse heterohybridoma.

Glycosylation of the human monoclonal IgG1 lambda antibody (mAb) CBGA1 was analysed by lectin blotting. The CBGA1 antibody binds to several antigens including donor self antigens, as detected by ELISA immunoblotting techniques and an erythrocyte binding assay. The mAb producing cell line was obtained by EBV transformation of peripheral blood lymphocytes of a healthy donor followed by fusion to the heteromyeloma cell line, CB-F7. The resulting heterohybridoma was cultivated in a hollow fibre bioreactor system. A bulk pool of 0.9 g antibody was produced. Fab and Fc fragments of the purified mAb were prepared and analysed. A noteworthy heterogeneity of CBGA1 and its fragments in SDS-PAGE and IEF was detected. We found glycosylation in the Fab fragment of CBGA1 in addition to the conserved glycosylation site in the Fc fragment at Asn 297. Fab glycosylation was detected in both the Fd region and the lambda-chain. The glycosylation pattern of the gamma-chain differs from that of the lambda-chain. Sequence analysis of the VH gene shows a potential N-glycosylation site located in framework III at position Asn 75.

Animals↗

Contamination profiles and characterisation of Bacillus species in wheat bread and raw materials for bread production.

The Bacillus counts in white and wholemeal wheat loaves produced without preservatives or sour dough were consistently 10(6) cfu/g after two days of storage at ambient summer temperatures (25-30 degree C). Identified species were B. subtilis (70%), B. licheniformis (24%), B. pumilus (2%) and B. cereus (2%). The dominance of B. subtilis in bread could be explained by the higher resistance to heat of this species as determined by inoculation studies. Among 14 species isolated from retail bread and wheat grains, B. subtilis was the only species associated with ropiness. Samples of raw materials, particularly bran, seeds and oat products, contained low levels (10(0) - 10(2) cfu/g) of Bacillus spores, surviving a heat treatment (100 degree C, 10 min) corresponding to a baking process. Even low spore levels in raw materials with the frequently isolated species, B. licheniformis (49%) and B. subtilis (10%), resulted in 10(7) Bacillus per g bread crumb in two days as determined by test bakings. The results indicate a need for controlling growth of Bacillus in bread.

Bacillus↗

Involvement of the GTP binding protein Rho in constitutive endocytosis in Xenopus laevis oocytes.

To study an endocytotic role of the GTP-binding protein RhoA in Xenopus oocytes, we have monitored changes in the surface expression of sodium pumps, the surface area of the oocyte and the uptake of the fluid-phase marker inulin. Xenopus oocytes possess intracellular sodium pumps that are continuously exchanged for surface sodium pumps by constitutive endo- and exocytosis. Injection of Clostridium botulinum C3 exoenzyme, which inactivates Rho by ADP-ribosylation, induced a redistribution of virtually all intracellular sodium pumps to the plasma membrane and increased the surface area of the oocytes. The identical effects were caused by injection of ADP-ribosylated recombinant RhoA into oocytes. The C3 exoenzyme acts by blocking constitutive endocytosis in oocytes, as determined using a mAb to the beta 1 subunit of the mouse sodium pump as a reporter molecule and oocytes expressing heterologous sodium pumps. In contrast, an increase in endocytosis and a decrease in the surface area was induced by injection of recombinant Val14-RhoA protein or Val14-rhoA cRNA. PMA stimulated sodium pump endocytosis, an effect that was blocked by a specific inhibitor of protein kinase C (Gö 16) or by ADP-ribosylation of Rho by C3. Similarly, the phorbol ester-induced increase in fluid-phase endocytosis in oocytes was inhibited by Gö 16, C3 transferase, or by injection of ADP-ribosylated RhoA. In contrast to C3 transferase, C. botulinum C2 transferase, which ADP-ribosylates actin, had no effect on sodium pump endocytosis or PMA-stimulated fluid-phase endocytosis. The data suggests that RhoA is an essential component of a presumably clathrin-independent endocytic pathway in Xenopus oocytes which can be regulated by protein kinase C.

ADP Ribose Transferases↗

Diagnostic imaging in children with urinary tract infection: the role of intravenous urography.

Ninety children referred to hospital with urinary tract infection (UTI) were investigated by iv urography (IVU), ultrasonography (US) and 99mTc dimercaptosuccinic acid scan (DMSA). Fifty-eight children also underwent micturating cystourethrography (MCUG). In 36 (40%) of the children, at least one result was abnormal. Abnormal findings were found in 29 children with IVU, in 10 with US and in 16 with DMSA. Six of the 58 children had vesicoureteric reflux (VUR) in 8 kidneys. In 16 children, IVU was the only examination with an abnormal result, and in 10 of these the findings were considered important for treatment or prognosis. IVU is an important supplement to US and DMSA in investigation programs for children with UTI. IVU should be performed in cases of renal scars, dilatations or in children with recurrent infections.

Adolescent↗

Stable expression of a functional GluR6 homomeric glutamate receptor channel in mammalian cells.

This study demonstrates the stable expression of a functional ionotropic glutamate receptor in a mammalian cell line of non-neuronal origin. The kainate-selective glutamate receptor GluR6 was constitutively expressed under the control of a metallothionein promoter. Clones were isolated expressing approximately 3 pmol of receptor per mg of protein. Functionality of the recombinant GluR6 was demonstrated both by electrophysiology and by Ca2+ imaging. Application of kainate to the GluR6-transfected cells activated an inward current response at a holding potential of -60 mV. The kainate concentration needed to evoke 50% of the maximal response (EC50) was calculated to be 0.82 +/- 0.39 microM. The current-voltage relationship was found to be almost linear, with a reversal potential of -2.5 +/- 4.8 mV. Application of kainate also resulted in an increase in the intracellular Ca2+ concentration measured by Ca2+ imaging. The pharmacological profile of [3H]kainate binding to the recombinant GluR6 resembled the high-affinity [3H]kainate binding sites in rat brain, showing high affinity for domoate (Ki = 5.1 +/- 3.0 nM) and kainate (Kd = 12.9 +/- 2.4 nM). No decrease in GluR6 expression level was observed over > 75 passages of the transfected cells. When domoate, a slowly desensitizing GluR6 agonist, was included in the growth medium for 3 weeks, the number of GluR6 binding sites decreased by 30%, indicating the importance of complete channel closure for stable expression.

Animals↗