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H H Rasmussen

Publications and source records attributed to H H Rasmussen.

At least 19 recordsLinked to original sources
PubMed2006

Apical sparing in tako-tsubo cardiomyopathy.

BACKGROUND: Tako-tsubo cardiomyopathy (TTC) is an acute reversible cause of segmental myocardial dysfunction that is poorly understood. We have noted a variant of this condition where a tiny segment at the apex retains some contractile function. This paper delineates the frequency of this variant relative to the classical form and the clinical differences between patients suffering from the two forms. METHODS: All cases of TTC (n = 35) were identified from our infarct angiography database and separated on the basis of apical sparing (n = 14) or no apical sparing (n = 21). RESULTS: Compared with the classical form, those with apical sparing were significantly younger (63 +/- 12 vs 72 +/- 13 years) and were more likely premenopausal (5/14 vs 0/21) and had higher ejection fractions (35 +/- 6% vs 32 +/- 4%). There was a trend towards higher recurrence (4/21 vs 0/14). There were no differences in time or season of presentation, precipitant stressor, premorbid drug therapy, haemodynamics at catheterization or acute outcomes. CONCLUSION: The apical sparing variant of TTC is common, accounting for 40% of cases. While the patients are younger and more likely premenopausal, there are no other distinguishing features between the classical and the variant form.

Age Factors↗
PubMed2001

Protein kinase Cepsilon contributes to regulation of the sarcolemmal Na(+)-K(+) pump.

A reduction in angiotensin II (ANG II) in vivo by treatment of rabbits with the angiotensin-converting enzyme inhibitor, captopril, increases Na(+)-K(+) pump current (I(p)) of cardiac myocytes. This increase is abolished by exposure of myocytes to ANG II in vitro. Because ANG II induces translocation of the epsilon-isoform of protein kinase C (PKCepsilon), we examined whether this isozyme regulates the pump. We treated rabbits with captopril, isolated myocytes, and measured I(p) of myocytes voltage clamped with wide-tipped patch pipettes. I(p) of myocytes from captopril-treated rabbits was larger than I(p) of myocytes from controls. ANG II superfusion of myocytes from captopril-treated rabbits decreased I(p) to levels similar to controls. Inclusion of PKCepsilon-specific blocking peptide in pipette solutions used to perfuse the intracellular compartment abolished the effect of ANG II. Inclusion of psiepsilonRACK, a PKCepsilon-specific activating peptide, in pipette solutions had an effect on I(p) that was similar to that of ANG II. There was no additive effect of ANG II and psiepsilonRACK. We conclude that PKCepsilon regulates the sarcolemmal Na(+)-K(+) pump.

Angiotensin II↗
PubMed2001

Cyclosporine and FK506 differentially regulate the sarcolemmal Na(+)-K(+) pump.

Cyclosporine A (CsA) and FK506, important immunosuppressants, have been shown to inhibit the enzymatic equivalent of the Na(+)-K(+) pump (Na(+), K(+)-ATPase) in renal tissue. A similar effect in the heart may contribute to the adverse effects of these agents that include calcification, contractile dysfunction, and altered calcium handling. However, inhibition of the pump has not been demonstrated in cardiac myocytes. We isolated single ventricular myocytes from control rabbits and from rabbits administered CsA or FK506 for 1 week. Na(+)-K(+) pump current (I(p)) was measured using the whole-cell patch-clamp technique. When patch pipettes contained Na(+) in a concentration ([Na](pip)) near physiological intracellular levels mean I(p) of cardiac myocytes from rabbits with serum CsA levels within the therapeutic range was significantly lower than mean I(p) of cardiac myocytes from controls. Treatment had no effect on I(p) measured using a [Na](pip) expected to nearly saturate intracellular binding sites. The CsA-induced inhibition of I(p) was dependent on the K(+) concentration in pipette solutions. Mean I(p) in myocytes from rabbits with serum levels of FK506 within the therapeutic range was similar to mean I(p) in myocytes from controls, whereas FK506 in a dose inducing serum levels severalfold above the therapeutic range caused significant pump inhibition. Using ion-sensitive microelectrodes we showed the intracellular Na(+) activity in papillary muscles isolated from rabbits treated with CsA was significantly higher than in papillary muscles from control rabbits, indicating that CsA causes pump inhibition in intact myocytes with a physiological intracellular milieu.

Animals↗
PubMed2000

[Clinical nutrition in Danish hospitals. A questionnaire study among physicians and nurses].

Specific nutrition standards have now been developed by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). We investigated the use of clinical nutrition in Danish hospitals and compared it with the standards of JCAHO by doing a questionnaire-based investigation among doctors and nurses randomly selected in 40 hospitals. Overall, 857 (43.4%) responded to the questionnaire (doctors: 395, nurses: 462). Forty percent found it difficult to identify risk-patients, and 52% needed specific screening tools. Eighty-four percent found that a nutrition plan should be described in the patient record, but 39% found it difficult to set up an individual plan, and 79% expressed a need for specific guidelines. The use of clinical nutrition in Danish hospitals did not fulfill the standards for nutrition support according to the criteria established by JCAHO. Special efforts should be aimed at education, specific screening tools and introduction of guidelines in clinical nutrition.

Denmark↗
PubMed2000

[Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography].

Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC). PET scanning can assess metabolism in vivo. The glucose analogue [18 F]fluoro-2-deoxy-D-glucose (FDG) accumulates in malignant tumours because of high glucose metabolism. PET scanning of the liver was performed after intravenous FDG in nine patients with PSC, six with PSC + CC, and five controls. "Hot spots" with radioactivity accumulation were seen in each PSC + CC patient, but not in the two other groups. Values of net metabolic clearance of FDG, K (ml min-1 100 ml-1 tissue), was in CC hot spots 1.59 to 4.17 (median, 2.34; n = 6); in reference liver tissues of these patients 0.40 to 0.69 (0.49); in PSC 0.23 to 0.53 (0.36); in controls 0.20 to 0.34 (0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < 0.001). FDG-PET may detect small CC tumours and be useful in therapeutic management of PSC.

Bile Duct Neoplasms↗
PubMed2000

HMG CoA reductase inhibition reduces sarcolemmal Na(+)-K(+) pump density.

OBJECTIVES: HMG CoA reductase inhibitors reduce cellular availability of mevalonate, a precursor in cholesterol synthesis. Since the cholesterol content of cell membranes is an important determinant of Na(+)-K(+) pump function we speculated that treatment with HMG CoA reductase inhibitors affects Na(+)-K(+) pump activity. METHODS: We treated rabbits and rats for 2 weeks with the HMG CoA reductase inhibitor lovastatin and measured Na(+)-K(+) pump current (I(p)) in isolated rabbit cardiac myocytes using the whole cell patch-clamp technique, K-dependent p-nitrophenyl phosphatase (p-NPPase) activity in crude myocardial and skeletal muscle homogenates, and vanadate-facilitated 3H-ouabain binding in intact skeletal muscle samples from rats. RESULTS: Treatment with lovastatin caused statistically significant reductions in I(p), myocardial and skeletal muscle K-dependent p-NPPase activity and 3H-ouabain binding in the myocardium and skeletal muscle. The lovastatin-induced decrease in I(p) was eliminated by parenteral co-administration of mevalonate. However, this was not related to cardiac cholesterol content. CONCLUSIONS: Treatment with lovastatin reduces Na(+)-K(+) pump activity and abundance in rabbit and rat sarcolemma.

4-Nitrophenylphosphatase↗
PubMed2000

Voltage-dependent stimulation of the Na(+)-K(+) pump by insulin in rabbit cardiac myocytes.

Insulin enhances Na(+)-K(+) pump activity in various noncardiac tissues. We examined whether insulin exposure in vitro regulates Na(+)-K(+) pump function in rabbit ventricular myocytes. Pump current (I(p)) was measured using the whole-cell patch-clamp technique at test potentials (V(m)s) from -100 to +60 mV. When the Na(+) concentration in the patch pipette ([Na](pip)) was 10 mM, insulin caused a V(m)-dependent increase in I(p). The increase was approximately 70% when V(m) was at near physiological diastolic potentials. This effect persisted after elimination of extracellular voltage-dependent steps and when K(+) and K(+)-congeners were excluded from the patch pipettes. When [Na](pip) was 80 mM, causing near-maximal pump stimulation, insulin had no effect, suggesting that it did not cause an increase in membrane pump density. Effects of tyrphostin A25, wortmannin, okadaic acid, or bisindolylmaleimide I in pipette solutions suggested that the insulin-induced increase in I(p) involved activation of tyrosine kinase, phosphatidylinositol 3-kinase, and protein phosphatase 1, whereas protein phosphatase 2A and protein kinase C were not involved.

Androstadienes↗
PubMed1999

Proteomics and immunohistochemistry define some of the steps involved in the squamous differentiation of the bladder transitional epithelium: a novel strategy for identifying metaplastic lesions.

Here, we present a novel strategy for dissecting some of the steps involved in the squamous differentiation of the bladder urothelium leading to squamous cell carcinomas (SCCs). First, we used proteomic technologies and databases (http://biobase.dk/cgi-bin/celis) to reveal proteins that were expressed specifically by fresh normal urothelium and three SCCs showing no urothelial components. Thereafter, antibodies against some of the differentially expressed proteins as well as a few known keratinocyte markers were used to stain serial cryostat sections (immunowalking) of biopsies obtained from bladder cystectomies of two of the SCC-bearing patients (884-1 and 864-1). Because bladder cancer is a field disease, we surmised that the urothelium of these patients may exhibit a spectrum of abnormalities ranging from early metaplastic stages to invasive disease. Immunohistochemical analysis revealed three types of non-keratinizing metaplastic lesions (types 1-3) that did not express keratins 7, 8, 18, and 20 (expressed by normal urothelium) and could be distinguished based on their staining with keratin 19 antibodies. Type 1 lesions showed staining of all cell layers in the epithelium (with differences in the staining intensity of the basal compartment), whereas type 2 lesions exhibited mainly basal cell staining. Type 3 lesions did not stain with keratin 19 antibodies. In cystectomy 884-1, type 3 lesions exhibited the same immunophenotype as the SCC and may be regarded as precursors to the tumor. Basal cells in these lesions did not express keratin 13, suggesting that the tumor, which was also keratin 13 negative, may have arisen from the expansion of these cells. Similar results were observed with cystectomy 864-1, which showed carcinoma in situ of the SCC type. SCC 864-1 exhibited both keratin 19-negative and -positive cells, implying that the tumor arose from the expansion of the basal cell compartment of type 2 and 3 lesions. Besides providing with a novel strategy for revealing metaplastic lesions, our studies have shown that it is feasible to apply powerful proteomic technologies to the analysis of complex biological samples under conditions that are as close as possible to the in vivo situation.

Biomarkers, Tumor↗
PubMed1999

A primary stenting strategy as an alternative to fibrinolytic therapy in acute myocardial infarction. An analysis of results in hospital and at 6 weeks and 6 months.

OBJECTIVE: To report the feasibility and results to 6 months of a primary stenting strategy in patients with acute myocardial infarction (AMI). DESIGN: Prospective, single-centre, observational study. SETTING: A tertiary referral teaching hospital (Royal North Shore Hospital, Sydney), July 1997 to November 1998. SUBJECTS: 102 (of 194) consecutive patients presenting to the emergency department with AMI who were eligible for fibrinolytic therapy, and for a primary stenting strategy. The first 50 patients were under 70 years of age, and had not had previous coronary artery bypass grafting (CABG). The following 52 patients included patients up to 80 years and with previous CABG. OUTCOME MEASURES: Major adverse cardiac and cerebrovascular events: death, reinfarction, cerebrovascular accident (CVA) and repeat target lesion revascularisation, in hospital, and at 6 weeks and 6 months. Minor in-hospital adverse events: bleeding requiring blood transfusion, vascular complications and new-onset heart failure. Time delays to treatment, and duration of hospital stay. RESULTS: Normal flow was established in the infarct-related artery in 97/102 patients (95%). Stenting, percutaneous transluminal coronary angioplasty (PTCA), CABG or medical therapy was performed in 74, 11, 9 and 8 patients, respectively. Minor in-hospital events, time delays and hospital stay were similar to those reported previously. At 6 weeks, major adverse cardiac and cerebrovascular events had occurred in 5% of patients (four repeat target lesion revascularisation and one reinfarction). By 6 months, repeat target lesion revascularisation had been performed in an additional 10% of patients. No deaths had occurred. CONCLUSIONS: A primary stenting strategy can be performed safely, without significant delays and with excellent short and intermediate term outcomes.

Adult↗
PubMed1999

A comprehensive protein resource for the study of bladder cancer: http://biobase.dk/cgi-bin/celis.

In our laboratories we are exploring the possibility of using proteome expression profiles of fresh bladder tumors (transitional cell carcinomas, TCCs; squamous cell carcinomas, SCCs) and random biopsies as fingerprints to subclassify histopathological types and as a starting point to search for protein markers that may form the basis for diagnosis, prognosis, and treatment. Ultimately, the goal of these studies is to identify signaling pathways and components that are affected at various stages of bladder cancer progression and that may provide novel leads in drug discovery. Here we present our ongoing efforts to establish comprehensive two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) databases of TCCs and SCCs which are being constructed based on the proteomic and immunohistochemical analysis of hundreds of fresh tumors, random biopsies and cystectomies received shortly after operation (http://biobase.dk/cgi-bin/celis).

Animals↗
PubMed1999

Short-term culturing of low-grade superficial bladder transitional cell carcinomas leads to changes in the expression levels of several proteins involved in key cellular activities.

Fresh, superficial transitional cell carcinomas (TCCs) of low-grade atypia (3 grade I, Ta; 6 grade II, Ta), as well as primary cultures derived from them were labeled with [35S]methionine for 16 h, between 2 and 6 days after inoculation. Whole protein extracts were subjected to IEF (isoelectric focusing) two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) followed by autoradiography. Proteins were identified by a combination of proteomic technologies that included microsequencing, mass spectrometry, 2-D PAGE immunoblotting and comparison with the bladder TCC protein database available on the internet (http://biobase.dk/cgi-bin/celis). Comparison of the IEF 2-D gel protein profiles of fresh tumors and their primary cultures showed that the overall expression profiles were strikingly similar, although differing significantly in the levels of several proteins whose rate of synthesis was differentially regulated in at least 85% of the tumor/culture pairs as a result of the short-term culturing. Most of the proteins affected by culturing were upregulated and among them we identified components of the cytoskeleton (keratin 18, gelsolin and tropomyosin 3), a molecular chaperone (hsp 28), aldose reductase, GST pi, metastasin, synuclein, the calreticulin precursor and three polypeptides of unknown identity. Only four major proteins were downregulated, and these included two fatty acid-binding proteins (FABP:FABP5 and A-FABP) which are thought to play a role in growth control, the differentiation-associated keratin 20, and the calcium-binding protein annexin V. Proteins that were differentially regulated in only some of the cultured tumors included alpha-enolase, triosphosphate isomerase, members of the 14-3-3 family, hnRNPs F and H, PGDH, hsp (heat-shock protein) 60, BIP, the interleukin-1 receptor antagonist, the nucleolar protein B23, as well as several proteins of yet unknown identity. The suitability of in vitro bladder tumor culture models to study complex biological phenomena such as malignancy and invasion is discussed.

Carcinoma, Transitional Cell↗
PubMed1999

Clinical nutrition in danish hospitals: a questionnaire-based investigation among doctors and nurses.

Specific nutrition standards are now developed by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) in order to improve the nutritional status in hospitalized patients. We investigated the use of clinical nutrition in Danish hospitals and compared it with the standards of JCAHO by doing a questionnaire-based investigation among doctors and nurses randomly selected in 40 hospitals including internal medicine, gastroenterology, oncology, orthopedic departments and intensive care units (ICU).Overall, 857 (43.4%) responded to the questionnaire (doctors: 395, nurses: 462). Seventy-seven percent stated that nutritional assessment ought to be performed on admission, but only 24% stated that it was a routine procedure. Forty percent found it difficult to identify risk-patients, and 52% needed specific screening tools. Twenty-two percent registered body weight in all patients, and 18% registered nutrient intake routinely. Eighty-four percent found that a nutrition plan should be described in the patient record, but 39% found it difficult to set up an individual plan, and 79% expressed a need for specific guidelines. Eighty-four percent would only accept a patient being on isotonic glucose and/or electrolyte infusion for < 5 days (42% for < 2 days), and 33% would only accept a weight loss of 5% before active nutrition was initiated. About 50% would be restrictive in supplying enteral or parenteral nutrition to patients with impaired liver or kidney function. Twenty-seven percent did not use active nutritional therapy at all. Seventy-six percent found that nutritional assessment should be performed during hospital stays, but only 23% monitored the nutritional status. Sixty-eight percent stated that responsibility should be assigned to one or more persons, but this was the case in only 20%The use of clinical nutrition in Danish hospitals did not fulfill the standards for nutrition support according to the criteria established by JCAHO. Special efforts should be aimed at education, specific screening tools and introduction of guidelines in clinical nutrition.

Adult↗
PubMed1999

Psoriasis upregulated phorbolin-1 shares structural but not functional similarity to the mRNA-editing protein apobec-1.

Earlier studies of psoriatic and normal primary keratinocytes treated with phorbol 12-myristate-1-acetate identified two low-molecular-weight proteins, termed phorbolin-1 (20 kDa; pI 6.6) and phorbolin-2 (17.6 kDa; pI 6.5). As a first step towards elucidating the role of these proteins in psoriasis, we report here the molecular cloning and chromosomal mapping of phorbolin-1 and a related cDNA that codes for a protein exhibiting a similar amino acid sequence. The phorbolins were mapped to position 22q13 immediately centromeric to the c-sis proto-oncogene. Transient expression of the phorbolin-1 cDNA in COS cells and by in vitro transcription/translation, yielded polypeptides that comigrated with phorbolins-1 and -2. Comparative sequence analysis revealed 22% overall identity and a similarity of 44% of the phorbolins to apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme; however, recombinant-expressed phorbolin-1 exhibited no cytidine deaminase activity, using either a monomeric nucleoside or apolipoprotein B cRNA as substrate, and failed to bind an AU-rich RNA template. Whereas the precise function of the phorbolins remains to be elucidated, the current data suggest that it is unlikely to include a role in the post-transcriptional modification of RNA in a manner analogous to that described for apobec-1.

APOBEC-1 Deaminase↗
PubMed1999

Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. A Danish 16-year nationwide follow-up study.

BACKGROUND: There are few epidemiologic data about the risk of acute pancreatitis in chronic inflammatory bowel diseases; we therefore wanted to estimate the risk of a first episode of acute pancreatitis in patients with Crohn's disease and ulcerative colitis in the total Danish population. METHODS: The study included all patients discharged from Danish hospitals with a diagnosis of Crohn's disease or ulcerative colitis registered in the Danish National Registry of Patients in the period from 1977 to 1992. The first episode of acute pancreatitis was identified in the cohort. The observed number of patients with acute pancreatitis was compared with expected numbers on the basis of age, sex, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,526 patients were discharged and followed up for 112,824 person-years. The standardized incidence ratio (SIR) for acute pancreatitis was increased both in patients with Crohn's disease (SIR = 4.3; 95% confidence interval (CI), 2.9-6.1) and in those with ulcerative colitis (SIR= 2.1; 95% CI, 1.6-2.8). CONCLUSION: Patients with chronic inflammatory bowel disease seem to be at increased risk of acute pancreatitis. Further validation and refinement of this registration-based study are needed.

Acute Disease↗
PubMed1999

Mechanisms of Na+-K+ pump regulation in cardiac myocytes during hyposmolar swelling.

We have previously demonstrated that the sarcolemmal Na+-K+ pump current (Ip) in cardiac myocytes is stimulated by cell swelling induced by exposure to hyposmolar solutions. However, the underlying mechanism has not been examined. Because cell swelling activates stretch-sensitive ion channels and intracellular messenger pathways, we examined their role in mediating Ip stimulation during exposure of rabbit ventricular myocytes to a hyposmolar solution. Ip was measured by the whole cell patch-clamp technique. Swelling-induced pump stimulation altered the voltage dependence of Ip. Pump stimulation persisted in the absence of extracellular Na+ and under conditions designed to minimize changes in intracellular Ca2+, excluding an indirect influence on Ip mediated via fluxes through stretch-activated channels. Pump stimulation was protein kinase C independent. The tyrosine kinase inhibitor tyrphostin A25, the phosphatidylinositol 3-kinase inhibitor LY-294002, and the protein phosphatase-1 and -2A inhibitor okadaic acid abolished Ip stimulation. Our findings suggest that swelling-induced pump stimulation involves the activation of tyrosine kinase, phosphatidylinositol 3-kinase, and a serine/threonine protein phosphatase. Activation of this messenger cascade may cause activation by the dephosphorylation of pump units.

Animals↗
PubMed1999

Angiotensin regulates the selectivity of the Na+-K+ pump for intracellular Na+.

Treatment of rabbits with angiotensin-converting enzyme (ACE) inhibitors increases the apparent affinity of the Na+-K+ pump for Na+. To explore the mechanism, we voltage clamped myocytes from control rabbits and rabbits treated with captopril with patch pipettes containing 10 mM Na+. When pipette solutions were K+ free, pump current (Ip) for myocytes from captopril-treated rabbits was nearly identical to that for myocytes from controls. However, treatment caused a significant increase in Ip measured with pipettes containing K+. A similar difference was observed when myocytes from rabbits treated with the ANG II receptor antagonist losartan and myocytes from controls were compared. Treatment-induced differences in Ip were eliminated by in vitro exposure to ANG II or phorbol 12-myristate 13-acetate or inclusion of the protein kinase C fragment composed of amino acids 530-558 in pipette solutions. Treatment with captopril had no effect on the voltage dependence of Ip. We conclude that ANG II regulates the pump's selectivity for intracellular Na+ at sites near the cytoplasmic surface. Protein kinase C is implicated in the messenger cascade.

Angiotensin II↗
PubMed1998

Molecular cloning of a cDNA encoding human calumenin, expression in Escherichia coli and analysis of its Ca2+-binding activity.

By microsequencing and cDNA cloning we have identified the transformation-sensitive protein No. IEF SSP 9302 as the human homologue of calumenin. The nucleotide sequence predicts a 315 amino acid protein with high identity to murine and rat calumenin. The deduced protein contains a 19 amino acid N-terminal signal sequence, 7 EF-hand domains and, at the C-terminus, a HDEF sequence which has been reported to function as retrieval signal to the ER. The calumenin transcript is ubiquitously expressed in human tissue, at high levels in heart, placenta and skeletal muscle, at lower levels in lung, kidney and pancreas and at very low levels in brain and liver. Calumenin belongs to a family of multiple EF-hand proteins that include the ER localized proteins reticulocalbin and ERC-55 and the Golgi localized Cab45. Since its Ca2+ binding may be important for the function of the protein we have used microdialysis experiments in order to analyse for the affinity and the capacity of recombinant human (rh) calumenin. All 7 EF-hands of the protein are functional and bind Ca2+, each with an affinity of 1.6x103 M-1. The relatively low affinity for the EF-hands may suggest a role for the protein in Ca2+-dependent processes in the ER.

Amino Acid Sequence↗