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Biomedical subjects

G Rasmussen

Publications and source records attributed to G Rasmussen.

At least 37 records · Page 2Linked to original sources

The effect of nimodipine on autoregulation of cerebral blood flow after subarachnoid haemorrhage in rat.

Disturbance of the autoregulation of the cerebral blood flow (CBF) is frequently seen following subarachnoid haemorrhage (SAH) and is possibly partly caused by cerebral ischaemia. It is well-known, that the calcium channel blocker nimodipine reduces the incidence of cerebral infarction and ischaemic dysfunction after SAH. The aim of the present study was to investigate the effect of nimodipine on autoregulation of CBF in an experimental model of SAH. The autoregulation was investigated in 10 control rats with SAH and in 10 nimodipine treated rats with SAH by serial measurements of CBF using a 133Xenon intracarotid injection method during controlled blood pressure manipulations. In the control rats the autoregulation was severely disturbed, no plateau was found where CBF was independent of changes in the arterial blood pressure (MABP). In rats treated with intravenous nimodipine (0.03 mg/kg body weight/h), CBF was 33.0% higher and MABP 5.3% higher compared with the controls. CBF was found constant in the MABP interval between 60 and 100 mmHg which indicates, that nimodipine improves the autoregulation of CBF after SAH.

Animals↗

An electron microscopic study of clinical Paget's disease of the nipple.

An ultrastructural study of the epidermis from eight patients with clinical Paget's disease of the nipple supports the epidermotropic theory. There was no evidence that the Paget's cells originated from keratinocytes. We propose the hypothesis that Paget's cells represent transformed ductal cells, from the subjacent lactiferous ducts of the nipple, which have migrated into the epidermis, either as neoplastic cells or as normal ductal cells with secondary in situ transformation in the epidermis.

Aged↗

Construction of SV40 deletion mutants and delimitation of the binding domain for heat shock protein to the amino terminus of large T-antigen.

SV40 large T-antigen (T-ag) mutants were generated using a cassette mutagenesis strategy and naturally occurring restriction sites. T-ag mutant constructs included internal in-frame deletions, frame-shift deletions that resulted in amino-terminal fragments, and internal initiation mutants that produced carboxy-terminal fragments; no foreign amino acids were introduced. The deletion mutants were stably expressed in BALB/c 3T3E cells and were analyzed for ability to bind heat shock cognate protein 70 using an ATP release assay of T-ag immunoprecipitates. Complex formation between heat shock protein and T-ag was independent of p53 involvement. The heat shock protein binding domain was narrowed to the amino-terminal 97 amino acids of T-ag, with the first 29 residues influencing the interaction. The amino-terminal domain of T-ag is important in both viral replication and cell transformation. We propose that the functional interactions of this highly interactive region of T-ag may be modulated by heat shock cognate protein 70.

3T3 Cells↗

Inhibition of G2/M progression in Schizosaccharomyces pombe by a mutant calmodulin kinase II with constitutive activity.

Intracellular signaling by the second messenger Ca2+ through its receptor calmodulin (CaM) regulates cell function via the activation of CaM-dependent enzymes. Previous studies have shown that cell cycle progression at G1/S and G2/M is sensitive to intracellular CaM levels. However, little is known about the CaM-regulated enzymes involved. Protein phosphorylation has been shown to be important for cell-cycle regulation. Because CaM regulates several protein kinases, and at least one protein phosphatase, our studies are focusing on the roles of these enzymes within the cell cycle. As an initial approach to this problem, cDNAs encoding either normal or mutant calcium/calmodulin kinase II (CaMKII) have been expressed in Schizosaccharomyces pombe. The results show that overexpression of a constitutively active mutant CaMKII caused cell-cycle arrest in G2. Arrest was associated with a failure to activate the p34/cdc2 protein kinase. Expression of the mutant CaMKII in strains of S. pombe with altered timing of mitosis revealed that this effect is not mediated either by cdc25+ or wee1+, suggesting that CaMKII may regulate G2/M progression by another mechanism.

Animals↗

[Chronic radiation enteropathy. A retrospective study].

In the period 1968-1989 50 patients, 38 women and 12 men, aged 30-76 years, median 58 years, were referred to the Department of Gastroenterology, Rigshospitalet for severe chronic radiation enteropathy. Most women had received radiation for gynaecological cancer, and most men for urogenital cancer. The initial symptoms of the enteropathy were diarrhoea in 74%, abdominal pain in 62% and weight loss in 52%. Twelve per cent had visible blood in the stools. Ten per cent had fistulas. The symptoms occurred 0-37 years, median ten months after the radiation. The radiation enteropathy had necessitated one or more laparotomies in 35 patients, most often because of subileus/ileus, including resection of the small bowel or the colon in 25 patients, and establishment of an ileostomy or a colostomy in 11. Seven patients developed new fistulas postoperatively. In 32 patients one or more tests for malabsorption were performed as a guidance for therapy: stool mass (26 patients), faecal fat excretion (26 patients), Schilling test (22 patients), lactose absorption (11 patients) and bile acid breath test (seven patients). Half of the patients had diarrhoea, including one third of the patients without intestinal resection. Two thirds had steatorrhoea, including half of the patients without small bowel resection. Three fourths showed decreased absorption of vitamin B12, including half of the patients without ileal resection. All patients studied had abnormal deconjugation of bile acids and more than half of them had bile acid malabsorption. Malabsorption of lactose was found in only one patient. There was no correlation between the radiological and functional abnormalities of the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stereochemistry, specificity and kinetics of the hydrolysis of reduced cellodextrins by nine cellulases.

The catalytic activity of nine enzymes (endoglucanases I-III, V, VI and cellobiohydrolases I and II from Humicola insolens; endoglucanases A and C from Bacillus lautus), representative of cellulase families A-C, H, J and K, has been investigated using a series of reduced cellooligosaccharides (cellotriitol to cellohexaitol) as substrates. For each enzyme, the specificity of cleavage was determined by analytical HPLC while the kinetic constants were obtained from a kinetic assay involving a cellobiose dehydrogenase purified from H. insolens as a coupled enzyme using 2,6-dichloroindophenol as the electron acceptor. These data were used to estimate the number of subsites in the enzymes. The stereochemical course of hydrolysis by seven enzymes, representing the six different families, was assessed using 1H-NMR. The enzymes belonging to families which had already been investigated (A-C), showed results in agreement with previous studies. The three other families (H, J and K), for which no mechanistic data was previously available, gave results which indicated that enzymes in group H had retaining-type activity and enzymes in groups J and K had inverting-type activity. The retaining endoglucanases I and III displayed a high glycosyl-transferase activity under the conditions used during the NMR experiments resulting in precipitates of higher oligomers.

Bacillus↗

Structure and function of endoglucanase V.

Cellulose is the major polysaccharide component of plant cell walls and is the most abundant organic compound on the planet. A number of bacterial and fungal organisms can use cellulose as a food source, possessing cellulases (cellobiohydrolases and endoglucanases) that can catalyse the hydrolysis of the beta-(1,4) glycosidic bonds. They can be classified into seven distinct families. The three-dimensional structures of members of two of these families are known. Here we report the structure of a third cellulase, endoglucanase V, whose sequence is not represented in any of the above families. The enzyme is structurally distinct from the previously determined cellulases but is similar to a recently characterized plant defence protein. The active site region resembles that of lysozyme, despite the lack of structural similarity between these two enzymes.

Binding Sites↗

Cerebral blood flow autoregulation after experimental subarachnoid hemorrhage during hyperventilation in rats.

The purpose of the current study was to investigate whether impaired cerebral blood flow (CBF) autoregulation after experimental subarachnoid hemorrhage (SAH) could be restored by hyperventilation. SAH was induced in rats by injection of autologous blood into the cisterna magna. CBF was measured using intracarotid injection of 133Xe. Autoregulation was studied in four groups of animals: normoventilated controls, hyperventilated controls, normoventilated animals with SAH, and hyperventilated SAH animals. PaCO2 in the normocapnic groups was 38-42 mm Hg and 25-30 mm Hg in the hypocapnic groups. CO2 reactivity after SAH was intact as hyperventilation decreased CBF by 38% in controls and by 46% in animals with SAH. Mean arterial pressure (MAP) was unaffected in both groups. In the controls, hypocapnia caused a shift of the autoregulation curve toward lower CBF levels without changing the lower limit of autoregulation. In the SAH group in the normocapnic state, autoregulation was absent as the obtained curve was a straight line, such that CBF increased with increasing MAP. However, during hypocapnia CBF was constant in the MAP interval between 60-150 mm Hg showing reestablishment of autoregulation by hyperventilation.

Animals↗

[Norwegian physicians and referral to chiropractors].

Two comparable surveys were carried out, one in 1979 and one in 1989, to study the practice of medical practitioners as regards referrals to chiropractors. Norway is the only country where reimbursement for chiropractic treatment from the National Health Insurance depends on referral by a medical practitioner. The survey investigated the attitude towards this system of referral, whether or not a uniform standard of practice existed in regard to musculoskeletal disorders, and what types of conditions are referred. A substantial percentage, 41.6, of the patients had not been examined by their medical doctor before the referral, and 23.9% had received their referral after the chiropractic treatment had started. A medical diagnosis was given in 84.3% of all cases, and x-ray findings were communicated to the chiropractors for 35.5% of the x-rayed patients. The surveys indicate that the present system of referrals does not function properly and may not be the best way of organizing the working relationship between medical doctors and chiropractors. The practice of referral had changed during the ten year period. In 1989, chiropractic was the first choice of treatment for patients with musculoskeletal problems more often than in 1979. Low back pain was the reason for the majority of referrals both in 1989 and in 1979. An apparent lack of standardization of diagnostic and therapeutic measures was demonstrated by comparing different regions of Norway. A marked discrepancy was found between rural and urban areas in the use of sick-leave and drug therapy.

Attitude of Health Personnel↗

[Use of thermotherapy, ultrasound and laser by practising physiotherapists. Physiotherapists' choice of treatment].

The purpose of this examination was to examine the practising physiotherapist's way of treating patients with nine selected diagnoses (fibrosites, osteoarthritis, rheumatoid arthritis, cervical slipped disc, lumbar slipped disc, generalized lumbar/back pain, generalized bursitis, generalized tendinitis, and sprains). In addition, nine different forms of therapy were examined (hot packs, infra-red light, ice packs, short waves, microwaves, diadynamic current, ultrasound, transcutaneous electric nerve stimulation and laser). All in all, 41 clinics with 2,018 treatment confrontations in the examination period, the last week of March 1990, took part in the survey. The majority of therapists were in possession of short wave, hot packs, ultrasound and laser which are also the four forms of therapy most frequently used for treatment. Compared to a Swedish examination from 1979, there is a doubling in ultrasound treatments from 24% to 48%, while the amount of short wave and microwave treatment remained unchanged. There was a remarkable variation in the physiotherapist's choice of therapy in each different diagnosed case. This can be due to the lack of specification of the diagnosis, so that different symptoms, course and stage of illness changed the treatment pattern elected.

Denmark↗

Cerebral blood flow autoregulation in experimental subarachnoid haemorrhage in rat.

Haemodynamic instability is of great importance in clinical management of patients with subarachnoid haemorrhage (SAH). The significance of angiographically demonstrable vasospasm for disturbances of cerebral blood flow (CBF) and cerebral autoregulation has not yet been clarified. The present study was designed to describe disturbances of cerebral autoregulation during the timecourse of experimental SAH (eSAH) in rats. A second aim of the study was to relate the results to a reported timecourse of angiographic vasospasm in the same animal model. Previous studies have shown that the timecourse of angiographically visible vasospasm in eSAH is biphasic with maximal spasm at 10 min and 2 days after induction of eSAH. At 5 days, the vasospasms have resolved. CBF was measured using a 133-Xenon intracarotid injection method which allowed serial measurements of mean hemispheric CBF during controlled manipulations of arterial blood pressure. In this way, an autoregulation curve could be constructed. The present study shows that autoregulation is severely disturbed or even totally absent at 2 and 5 days after eSAH. Thus there seems to be no direct correlation between presence of angiographic vasospasm and impairment of autoregulation, or that the impairment of autoregulation is more protracted than the presence of cerebral vasospasm, presuming a correlation exist.

Acid-Base Equilibrium↗

[Surgical treatment of cervical spondylotic myelopathy. A follow-up study].

The effect of operative treatment of spondylotic cervical myelopathy (SCM) was assessed by a follow up investigation of 33 patients submitted consecutively to operation. The patients were followed up on an average two years and two months after operation. As compared with the preoperative status, 39% of the patients had improved, 27% remained unchanged and 33% had a clinical status which was poorer than preoperatively. Age and sex were not found to be of significance for the prognosis. Patients with brief case histories had better effects of operation than patients with prolonged duration of the condition. The best results were found in patients in whom the duration of the condition was less than one year. Although 66% patients had obtained improved clinical condition or in whom progression of the condition has been arrested, 82% of the patients had been awarded social pensions at follow up examination as compared with 48% preoperatively. It is concluded that treatment of SCM should be instituted as early as possible in the course of the condition in the form of operative decompression of the cervical medulla.

Adult↗

Solubilization of SV40 plasma-membrane-associated large tumor antigen using single-phase concentrations of 1-butanol.

The nature of the interaction of the simian virus 40 (SV40) transforming protein, large tumor antigen (T-ag), with the plasma membrane of transformed cells is not well understood. We report here that SV40 plasma-membrane-associated large tumor antigen (pmT-ag) can be solubilized by using single-phase concentrations of 1-butanol. Purified plasma membranes from SV40-transformed mouse cells yielded T-ag when treated with 2.5% butanol; solubilization of T-ag from the purified membranes in butanol was temperature dependent, with approximately 10-fold more T-ag extracted at 37 degrees C than at 22 degrees C; and application of 2.5% butanol to mKSA cells after cellular surface proteins had been radiolabeled with 125I resulted in the release of iodinated T-ag. Butanol-extracted pmT-ag coprecipitated with p53 and several cellular proteins ranging in size from 35 to 60 kDa. One cellular component migrated at a mobility similar to that of tubulin (56 kDa), and a monoclonal antibody against the alpha subunit of tubulin coprecipitated T-ag. Immunoblotting of proteins immunoprecipitated with monoclonal antibodies against T-ag or p53 from butanol extracts with a monoclonal antibody against the beta subunit of tubulin revealed specific coprecipitation of tubulin with T-ag and p53. This suggests that complexes composed of tubulin, T-ag, and p53 exist in butanol extracts. Control experiments eliminated the possibility of an artifactual association of tubulin with T-ag and p53 induced by butanol. Two-dimensional gel analyses revealed that 2.5% butanol at 37 degrees C extracted a subset of membrane-associated proteins and some cytosolic proteins, as well as a number of proteins that were not soluble in either high salt or detergent. Thus, the butanol extraction conditions employed in this study recovered a species of pmT-ag that appears to complex with tubulin. As butanol reportedly is less deleterious to native protein structures than other agents, including high salts and detergents, this extraction procedure may be useful for studying the structure and function of other membrane-associated proteins.

1-Butanol↗

Influence of the oral hypoglycemic agent linogliride (McN-3935) on insulin secretion from isolated rat islets of Langerhans.

The influence of a new orally effective hypoglycemic compound, linogliride (McN-3935), on insulin release from isolated perifused rat islets was investigated. At a concentration of 100 microM, linogliride was without effect on insulin secretion in the absence of glucose. While 5.5 mM glucose alone produced a weak secretagogue effect, the secretory response was dramatically (5- to 6-fold) increased by the addition of 100 microM linogliride. This concentration of linogliride did not affect the conversion of [5-3H]glucose to 3H2O, a measure of the rate of glycolysis by the islet. Insulin secretion in response to the combination of 100 microM linogliride and 5.5 mM glucose was abolished by the omission of extracellular calcium. Mannoheptulose (10 mM), an inhibitor of glucose phosphorylation and glucose-stimulated insulin secretion, markedly attenuated the insulinotropic effect of linogliride in parallel with reduced glucose usage. Paradoxically, in the presence of another metabolic inhibitor, 2-deoxyglucose (10 mM), the insulinotropic effect of linogliride (100 microM) in the presence of 5.5 mM glucose was not diminished despite the reduced glucose usage. Linogliride significantly increased the secretory response to other secretagogues, including 2.5 mM D-glyceraldehyde, 15 mM N-acetylglucosamine, 10 mM leucine, and 100 nM of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. These data suggest that linogliride amplifies a cellular signal generated during beta-cell activation by various stimulants.

Animals↗

CSF-dynamics in syringomyelia: intracranial pressure and resistance to outflow.

The several theories on the pathogenesis of syringomyelia have not resulted in the satisfactory selection of those patients who can be treated by CSF diversion. In the present paper three types of syringomyelia are described by case studies. The classification is made by investigation of CSF-dynamics, a measurement of CSF pressure and resistance to outflow of CSF. It is proposed that in a subgroup of patients with syringomyelia the cause is defective CSF resorption and that this group may be selected out and treated accordingly.

Adult↗