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Biomedical subjects

H Hansen

Publications and source records attributed to H Hansen.

At least 91 records · Page 5Linked to original sources
PubMed1996

Elbow synovectomy in rheumatoid arthritis.

We present the results of a clinical and radiographic follow-up study of patients undergoing elbow synovectomies. Twenty-five elbows in 24 patients with rheumatoid arthritis were followed for a median period of 52 months (range 10-108) after operation. Nineteen (74%) stated they had improvement of pain and function. Two patients reported increased pain. Improvement of motion was noted, but this was not statistically significant. Radiographic classification showed statistically significant progressive changes. Three complications were noted, all without permanent sequels. Moderate elbow destruction can provide a good indication for elbow synovectomy in the treatment of patients suffering from rheumatoid arthritis.

Adult↗
PubMed1996

Activation of conventional mammalian protein kinase C isoforms expressed in budding yeast modulates the cell doubling time--a potential in vivo screen for protein kinase C activators.

Conventional mammalian protein kinase C (PKC) isoforms alpha, beta 1, and gamma were expressed in Saccharomyces cerevisiae and resulted in a differential increase in the yeast doubling time in response to distinct classes of PKC activators. Mutants were created in the regulatory domain of PKC alpha to map the interaction with the different activators. The macrocyclic lactone bryostatin 5 preferentially regulated PKC alpha activity through the second cysteine-rich sequence (CYS2) of Cl, while regulation by the diterpene ester mezerein displayed strong preference for the first cysteine-rich sequence (CYS1) of Cl. The phorbol esters phorbol-12-myristate-13-acetate (PMA) and 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA) regulated PKC enzymatic activity equally potently via CYS1 or CYS2 albeit at reduced levels compared with native PKC alpha. For the diterpene ester ingenol-3, 20-dibenzoate and the indol alkaloids (-)-7-octyl-indolactam V and (-)-indolactam V, no responses were observed for mutants lacking either CYS1 or CYS2 whereas native PKC alpha activity was regulated. These in vivo results were complemented by in vitro binding and catalytic assays which showed correlation between PKC enzymatic activity and the cell growth characteristics. The observed phenotype can be exploited to screen natural compounds in vivo for their PKC regulatory potential and to map the underlying interactions.

Animals↗
PubMed1996

[Surgical treatment of fecal incontinence].

27 patients suffering from anal incontinence (4 male, 23 female) were treated in 22 cases with suture of the anal sphincters and in 5 cases with sublevatorial implantation of a silicone ring. A questionnaire and a follow up examination 0.5-10 years (median 3.5 years) after operation were carried out. 4 patients after anal sphincter suture could not be followed. In 2 cases of sphincter suture a final colostomy had been performed. 2 silicone rings had been removed because of infection or rupture. After reconstruction of the anal sphincter 5 patients felt complete continent; 9 were continent for solid stool; 2 complained about incontinence. In the group treated with silicone ring implantation, 1 patient felt completely and 2 partially continent. Subjective assessment and objective measuring of the quality of anal continence did not correlate. For the most part the results of subjective assessment appeared less favourable than might be expected form the values measured. Objectively a rise in all anal pressure values to a normal level was in most cases detectable. Compared to prior values this increase of anal tonus is significant.

Adult↗
PubMed1995

[Changes in neonatal mortality and morbidity of very low birth infants in the county of Nordjylland].

The purpose of the study was to investigate changes in neonatal mortality and morbidity in infants with very low birthweight born in the county of northern Jutland, Denmark. The study was retrospective and included infants with birthweight < or = 1500 grams born in northern Jutland. The period 1988-1989 was compared to the period 1990-1993. Two hundred and seventy (270) infants were included. A decrease in neonatal mortality from 27% to 18% was found, and for infants with birthweight < or = 1000 grams the neonatal mortality declined from 60% to 28%. Possible explanations were a higher frequency of betamethasone administration and the introduction of surfactant into routine medical care. The median birthweight declined by just under 100 grams. The frequency of clinically significant periventricular haemorrhage and the frequency of bronchopulmonary dysplasia did not increase. Long-term follow-up is necessary for the evaluation of the final results of the increased neonatal survival.

Denmark↗
PubMed1995

Shedding of the soluble form of CD30 from the Hodgkin-analogous cell line L540 is strongly inhibited by a new CD30-specific antibody (Ki-4).

The CD30-activation marker was detected as the Hodgkin-associated Ki-I antigen and is regarded as a target for the treatment of Hodgkin patients with immunotoxins. The CD30 is released from tumor cells and this soluble CD30 (sCD30) is an indicator of the disease activity. Since the shedding of sCD30 may be influenced by antibodies, we produced 6 new CD30-specific antibodies (Ki-2 to Ki-7) for the purpose of finding antibodies that might inhibit the formation of sCD30. Ki-2 to Ki-7 and the other anti-CD30 antibodies Ki-I, Ber-H2, HeFi-I, M44, M67, HRS-I, HRS-4 and C10 were employed for epitope mapping. The binding of a particular radio-labeled anti-CD30 antibody to Hodgkin's-disease-derived L540 cells was completed by addition of the various non-labeled anti-CD30 antibodies. Three non-overlapping regions, expressing different antigen-specific determinants, could be defined on the extracellular part of the CD30 molecule. Cluster A of determinants was recognized by Ki-2, Ki-4, Ki-6 and Ki-7, Ber-H2, HRS-I and HRS-4, while cluster B was detected by Ki-I, Ki-5 and M67. Cluster C, which probably contains the binding site for the CD30 ligand, was defined by Ki-3, M44, HeFi-I and C10. Co-culture experiments of L540 cells with the various antibodies followed by the isolation of sCD30 from culture supernatant fluids revealed that the release of sCD30 was most strongly increased by Ki-I and weakly enhanced by Ki-2, Ki-3, Ki-5 and HeFi-I, whereas it was almost completely inhibited by Ki-4 and to a slightly lesser extent by Ber-H2.

Animals↗
PubMed1995

Differential protein kinase C ligand regulation detected in vivo by a phenotypic yeast assay.

The molecular dissection of protein kinase C (PKC) action has been based in part on time-consuming functional assays such as the mouse skin model for testing the tumor promoter activity of phorbol esters and related PKC activators. To help overcome the limitations imposed by the complexity of such assays, we developed the yeast Saccharomyces cerevisiae as an alternative, rapid, and simple experimental system. This model has a specific phenotype, an increase in the cell doubling time, that is proportional to the level of enzymatic activity of expressed mammalian PKC isoforms. We used this phenotype to assay and compare the regulation of native bovine PKC alpha and mutants in the conserved regulatory region C1 in vivo by various activators: two diterpenes, the phorbol ester phorbol-12-myristate-13-acetate (PMA) and mezerein, and the indole alkaloid indolactam V. We found that PMA activated PKC mutants lacking either Cys-rich, zinc finger-like repeat of the conserved region C1 to comparably reduced levels, whereas indolactam V activated native PKC alpha but none of the mutants at normal doses. In contrast, mezerein activated native PKC alpha and a mutant lacking the second Cys repeat equally well but mutants lacking the first Cys repeat of C1 at a greatly reduced level. These differential responses were supported by the observed in vitro PKC catalytic activities. Therefore, PMA regulates PKC alpha activity comparably well via either Cys repeat, whereas mezerein regulation predominantly occurs via the first Cys repeat of C1. Indolactam V activation was less potent, it was greatly reduced in the absence of either Cys repeat, and displayed no preference. We introduce this phenotypic assay as a rapid and general screen for the PKC-activating or possibly inhibitory potential of drug candidates and to identify the PKC regulatory sites involved in these interactions.

Animals↗
PubMed1995

Evidence of the coevolution of a snake toxin and its endogenous antitoxin cloning, sequence and expression of a serum albumin cDNA of the Chinese cobra.

A full-length cDNA of the serum albumin (CSA) of the cobra (Naja naja kaouthia) was cloned from a lambda gt 11 library. It encodes a mature protein of 614 amino-acid residues homologous to the precursor of mammalian serum albumins. The 1 degree and 2 degrees structures of the CSA resemble those of the human variety. The putative toxin binding sites are mainly located in the subdomains IIA and IIIA. The relation between structural homology and function of the serum albumins (SA) is discussed. An analysis of their evolutionary tree revealed that anti-toxicity arose by < 90 amino-acid exchanges. The rate of substitution is much higher in the SA than in cytochrome C, which probably reflects the difference in evolutionary driving forces. The evolutionary period of the SA (6.7 +/- 0.1 M.Y.) significantly exceeds that of hemoglobin (5.8 M.Y.). Eight tripeptides in the nicotinic acetylcholine receptor (ACR), all flanking the putative toxin binding site, are also found in the CSA where they join to form 1 octa-, 1 penta- and 4 tripeptides, thus indicating the concerted evolution of two functionally linked proteins: toxin and antitoxin (CSA).

Amino Acid Sequence↗
PubMed1995

Team development and memory training in traumatic brain injury rehabilitation: two birds with one stone.

The need for developing team cooperation procedures when treating patients with traumatic brain injury (TBI) is stated. One approach in promoting team cooperation is to combine team development with a specific training programme. A memory training programme used in a subacute TBI rehabilitation unit is described. A combination of a team development procedure and memory training programme was performed in the unit. A questionnaire to assess team members' attitudes to team cooperation was administered before and after team development, and memory training procedures were implemented. The post-training questionnaire administration indicated a more positive perception among team members of how the team functioned. The efficacy of memory training showed variable results. The programme described may illustrate the advantages of combining a specific treatment programme with efforts to promote team development.

Adult↗
PubMed1994

A practical alternative to conventional five-field irradiation postmastectomy for locally advanced breast cancer.

A combination of electron and photon beams has been used as an alternative for the conventional five-field method to irradiate patients postmastectomy for locally advanced breast cancer. Anterior and posterior opposed photon beams treat in continuity the lateral chest wall, axilla, and supraclavicular lymph nodes. An adjacent anterior electron beam is used at an energy matched to the depth of the internal mammary nodes. It includes the anterior chest wall, but bolus is used in the lateral aspect to spare underlying lung. This electron beam eliminates the diverging junction between the internal mammary and medial tangential fields used in the conventional five-field technique. Overlaps along the junction between the photon and electron beams are minimized by placing the center of the photon field along its medial border. Measurements with an Alderson-Rando phantom show dose-distribution advantages for this technique over the conventional five-field approach. There is less chance of underdosing tumor cells or of overdosing normal tissue along beam junctions. Clinical studies on 29 patients treated by this technique between July 1985 and December 1989 show increased rates of acute skin reactions, but otherwise similar side effects compared with 57 breast cancer patients treated with the five-field technique over the same time period. Local recurrence rates and patient survival rates were similar for the two groups. Given the dose-distribution advantages of this technique and its simple adaptation to accommodate unusual surgical scars or cancer recurrences, its use should be considered for postmastectomy patients with locally advanced breast cancer in well-equipped cancer treatment centers.

Breast Neoplasms↗
PubMed1994

Ligand regulation of bovine protein kinase C alpha response via either cysteine-rich repeat of conserved region C1.

Based on the finding by others that the conserved region C1 of conventional protein kinase C isoforms carries two independent, cysteine-rich phorbol ester binding sites, we have mapped the structural elements of the C1 region for their role in the phorbol ester- and phospholipid regulation of PKC alpha responses. We have prepared two amino terminal truncation mutants of bovine PKC alpha, ND91 lacking the first Cys-repeat of C1, and ND153 lacking both Cys-repeats of C1, as well as two internal deletion mutants, D162-245 lacking most of C2, and D109-263 lacking most of C2 and the second Cys-repeat of C1. The mutants were expressed in the yeast Saccharomyces cerevisiae which allows the rapid biochemical and physiological characterization of mammalian PKC isoforms. We found that all mutants displayed an elevated basal level of enzymatic activity in vitro but retained the basic catalytic PKC characteristics: regulation by Ca2+ and (except for ND153) by phospholipid or phorbol ester. In vivo we observed proportional physiological responses, the stimulation of Ca2+ uptake, and an increase in the cell doubling time for all mutants upon phorbol ester stimulation (constitutive for ND153) similar to the response of normal PKC alpha. Our findings indicate that after partial PKC activation by deletion mutagenesis, the presence of either Cys-repeat in C1 still allows phospholipid- and phorbol ester regulation of protein kinase C alpha responses.

Animals↗
PubMed1994

The Alcoholism Denial Assessment Tool (ADAT): a study of interrater reliability.

The purpose of this study was to develop and test a tool for assessing alcoholic denial. The primary author devised the Alcoholism Denial Assessment Tool (ADAT) based on 2 years of experience. The tool was tested for interrater reliability using chart data of 42 recently discharged alcoholism patients. The test for significance of a proportion, using z scores, indicated significance at the .001 level. Item analysis showed strong interrater reliability on all but 1 of the 16 tool items. The ADAT provides nurses with a practical assessment tool that can be used daily to monitor progress. Recognition that a patient is in denial can allow meaningful and appropriately planned treatment.

Adolescent↗
PubMed1993

Stimulation of calcium uptake in Saccharomyces cerevisiae by bovine protein kinase C alpha.

Ca2+ plays essential roles as a second messenger often in synergism with the calcium- and phospholipid-dependent phorbol ester receptor, protein kinase C (PKC), which stimulates Ca2+ influx in various cell types in a potential positive feedback mechanism. To address the compatibility of these mechanisms between lower eukaryotes and mammals, we have stably expressed bovine PKC alpha in the yeast Saccharomyces cerevisiae. We find that phorbol ester binding sites are created which stimulate a specific calcium- and phospholipid-dependent catalytic activity in vitro. Phorbol ester activation in vivo stimulates PKC down-regulation, uptake of extracellular Ca2+, Ca2+ dependence of cell viability, and changes in cell morphology. This may represent activation of a putative PKC-mediated signaling pathway utilized by functional yeast homologs of mammalian PKC isoforms. These are suggested by some protein data; however, their genes have not yet been characterized (Simon, A. J., Milner, Y., Saville, S. P., Dvir, A., Mochly-Rosen, D., and Orr, E. (1991) Proc. R. Soc. Lond. B 243, 165-171). Our findings indicate that bovine PKC alpha is functional in yeast and stimulates calcium uptake in a manner similar to some of its responses in mammalian cells, which suggests compatible aspects of higher and lower eukaryotic signaling pathways and the feasibility of dissecting parts of the action of common signaling mediators in a simple genetic model.

Amino Acid Sequence↗
PubMed1993

Phorbol ester activation of functional rat protein kinase C beta-1 causes phenotype in yeast.

The phorbol ester receptor protein kinase C (PKC) gene family encodes essential mediators of various eukaryotic cellular signals. The molecular dissection of its mechanisms of action has been limited in part by the genetic inaccessibility and complexity of signaling in mammalian cells. Here we present a novel approach to study rat PKC beta-1 action in yeast, a simple lower eukaryotic genetic model. Expression of its cDNA in Saccharomyces cerevisiae introduces novel phorbol ester binding sites which stimulate a specific calcium- and phospholipid-dependent catalytic activity in vitro consistent with a fully functional protein which phosphorylates cellular yeast proteins in vivo. Phorbol ester activation of PKC beta-1 in vivo results in biological responses which include stimulation of extracellular calcium uptake, changes in cell morphology, and an increase in the cell doubling time. These PKC functions are not affected by truncation of 12 amino terminal amino acids; however, they are completely abolished by truncation of 15 or more carboxyl terminal amino acids which likely result in inactivation of the kinase. The increase in the yeast doubling time caused by PKC beta-1 activation provides a phenotype which can be exploited as a screen for the activity of random PKC cDNA mutations. Our findings indicate that rat PKC beta-1 is functional in yeast and leads to biological responses which suggest compatible aspects of higher and lower eukaryotic signaling pathways and the feasibility of dissecting parts of the action of common signaling mediators in a simple genetic model.

Amino Acid Sequence↗
PubMed1993

The effect of indomethacin upon cerebral blood flow in healthy volunteers. The influence of moderate hypoxia and hypercapnia.

In a randomized study of healthy volunteers indomethacin bolus injection followed by continuous infusion decreased CBF from normal levels ranging from 45 to 80 ml/100 g/min to levels ranging from 24 to 57 ml/100 g/min. These low levels were sustained during a six hour infusion period. Periods of hypoxia during inhalation of 17% oxygen and hypercapnia during inhalation of 2-4% CO2 normalized CBF.

Adolescent↗
PubMed1993

Three different mask physiotherapy regimens for prevention of post-operative pulmonary complications after heart and pulmonary surgery.

OBJECTIVE: An investigation into the incidence of post-operative complications after thoracic surgery with 3 different physiotherapy masks. DESIGN: A prospective, consecutive, randomized comparison. SETTING: Department of Thoracic and Heart Surgery at a University Hospital. The treatments were performed by experienced and specially trained physiotherapists. PATIENTS: 160 patients were evaluated. 60 patients undergoing heart surgery, 59 patients having pulmonary resection, and 41 patients with exploratory thoracotomy. INTERVENTIONS: In each operative category the patients were treated with one of three face mask systems used in addition to routine chest physiotherapy. These were either continuous positive airway pressure (CPAP), positive expiratory pressure (PEP), or inspiratory resistance - positive expiratory pressure (IR-PEP). MEASUREMENTS AND RESULTS: Post-operative pulmonary complications were assessed by forced vital capacity (FVC), arterial oxygen tension (PaO2), and chest X-ray examination, all measured pre-operatively and on the fourth and ninth post-operative day. The patients filled in a questionnaire expressing their opinion about their mask treatment. There was an equal decrease in FVC, FVC%, and PaO2, and equal frequency of atelectasis in the 3 mask treatments. More patients with the PEP mask favoured their system than did those with the other 2 systems. CONCLUSION: There was no statistically significant difference between the treatments: continuous positive airway pressure (CPAP), positive expiratory pressure (PEP), and inspiratory resistance - positive expiratory pressure (IR-PEP) on post-operative complications. Any of the three treatments may be used as supplement to standard chest physiotherapy.

Blood Gas Analysis↗