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Biomedical subjects

K Haglund

Publications and source records attributed to K Haglund.

At least 19 recordsLinked to original sources
PubMed2006

Cbl escapes Cdc42-mediated inhibition by downregulation of the adaptor molecule betaPix.

The Pix/Cool proteins are involved in the regulation of cell morphology by binding to small Rho GTPases and kinases of the Pak family. Recently, it has been shown that betaPix/Cool-1 associates with the ubiquitin ligase Cbl, which appears to be a critical step in Cdc42-mediated inhibition of epidermal-growth-factor-receptor (EGFR) ubiquitylation and downregulation. Here we show that the SH3 domain of betaPix specifically interacts with a proline-arginine motif (PxxxPR) present within the ubiquitin ligase Cbl and Pak1 kinase. Owing to targeting of the same sequence, Cbl and Pak1 compete for binding to betaPix. In this complex, Cbl mediates ubiquitylation and subsequent degradation of betaPix. Our findings reveal a double feedback loop in which the Cdc42/betaPix complex blocks Cbl's ability to downregulate EGFR, while Cbl in turn promotes degradation of betaPix in order to escape this inhibition. Such a relationship provides a mechanism to fine-tune the kinetics of RTK endocytosis and degradation depending on the pool of active Cdc42 and the duration of EGFR signaling.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Psychiatric wards with locked doors--advantages and disadvantages according to nurses and mental health nurse assistants.

AIMS AND OBJECTIVE: To describe nurses' and mental health nurse assistants' perceptions of advantages and disadvantages about working on a psychiatric ward with a locked entrance door. BACKGROUND: Psychiatric staff sometimes needs to protect patients from harming themselves or others. To keep the entrance door locked may help staff to achieve this goal. How locked entrance doors at psychiatric wards are experienced by staff, working on these wards, has been investigated to a very limited extent. DESIGN: The study was explorative and descriptive. METHOD: Audio taped, semi-structured interviews with open-ended questions about advantages and disadvantages about working on a psychiatric ward with a locked entrance door, were conducted with 20 nurses and 20 mental health nurse assistants. Data were analyzed with content analysis. RESULTS: A content analysis revealed eight categories of advantages and 18 categories of disadvantages. Most advantages mentioned by nurses and mental health nurse assistants were categorized as providing staff with control over patients, providing patients with a secure and efficient care and protecting patients and staff against 'the outside'. Most disadvantages mentioned by nurses were categorized as causing extra work for staff, making patients feel confined, making patients feel dependent and creating a non-caring environment. Most disadvantages mentioned by mental health nurse assistants were categorized as causing extra work for staff, making patients feel confined, causing emotional problems for patients, making staff's power obvious and forcing patients to adapt to other patients' needs. Nurses and mental health nurse assistants mentioned more disadvantages than advantages and nurses mentioned more disadvantages than mental health nurse assistants. CONCLUSION: Nurses and mental health nurse assistants perceive a number of advantages and disadvantages for themselves, patients and significant others with a locked door at a psychiatric ward. Most of these concern patients' experiences. RELEVANCE TO CLINICAL PRACTICE: It is important for staff working within psychiatric care to reflect upon the fact that a locked entrance door is connected with a range of negative as well as positive perceptions and to minimize patient and own concerns connected to the locked door.

Adult↗
PubMed2004

Medication administration in inpatient psychiatric care--get control and leave control.

The aim of this mini-ethnographic study was to describe medication administration (MA) in short-time inpatient psychiatric care. MA was observed on two psychiatric wards. Field-notes were taken and interviews were conducted with 15 voluntarily admitted patients and nine nurses. The data analysis was conducted as a dialectical and interactive process. Two central categories were generated: get control and leave control, and two subcategories: interpersonal contact and nurses' knowledge. The patients left control over medication to the nurses and expressed gratefulness for the opportunity to do so. Interpersonal contact between patients and nurses and nurses' knowledge were of importance for the possibility for the nurses to get control and for the patients to leave control. MA is a complex task with an importance beyond giving the right pill to the right patient, and provides patients with an opportunity to communicate with the nurses.

Adult↗
PubMed2003

Distress, quality of life and strategies to 'keep a good mood' in patients with carcinoid tumours: patient and staff perceptions.

Patients with carcinoid tumours have reported a relatively good health-related quality of life (HRQoL) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, EORTC QLQ-C30), and low levels of anxiety and depression (Hospital Anxiety and Depression Scale, HADS). The aim was to test the validity of these results. Data were gathered through interviews with 19 patients and 19 staff. Participants were asked about disease and treatment related distress, important aspects of quality of life and strategies to 'keep a good mood'. Patients were interviewed about themselves and staff were interviewed about a certain patient. Data were analysed by content analysis. Identified aspects of distress and quality of life were referred to an emotional, a physical and a social dimension. Most aspects of distress were of a physical character whereas most aspects of quality of life were of a social character. Several aspects of emotional distress not included in the EORTC QLQ-C30 and/or the HADS were identified.

Adaptation, Psychological↗
PubMed2003

Forced medication in psychiatric care: patient experiences and nurse perceptions.

The aims of this study were to describe: patient experiences of and nurse perceptions of patient experiences of forced medication before, during and after forced medication; patient and nurse perceptions of alternatives to forced medication; and whether patients, according to patients and nurses, retrospectively approved of forced medication. Eleven patients and nurses were interviewed about a certain situation of forced medication. Data were analysed by content analysis. The findings demonstrate that forced medication evokes a number of patient experiences according to patients and nurses. These are related to the disease, the situation of being forcibly medicated and the drug. Patients mentioned several alternatives to the forced medication, whereas nurses mentioned no alternatives. A minority of the patients, and not as many patients as the nurses' thought, retrospectively approved of the use of forced medication. It can be concluded that patients and nurses do not share the same perceptions about what patients experience when forcibly medicated.

Attitude of Health Personnel↗
PubMed2001

Homeobox gene Cdx1 regulates Ras, Rho and PI3 kinase pathways leading to transformation and tumorigenesis of intestinal epithelial cells.

The Cdx1 homeobox gene encodes for an intestine-specific transcription factor involved in the control of proliferation and differentiation of epithelial cells. Although it has been indicated that Cdx1 may act as a proto-oncogene in cultured fibroblasts, its direct role in the regulation of intestinal tumorigenesis has not been demonstrated. Here we show that expression of Cdx1 in an intestinal epithelial cell line (IEC-6) induces anchorage-independent growth in soft agar and promotes the formation of adenocarcinoma in vivo. The phenotype of Cdx1-induced tumors was exacerbated when IEC-6/Cdx1 cells were injected together with matrigel containing mitogens and extracellular matrix components. These changes were correlated with an increase in the GTP-bound form of Ras, modulation of Cdc42 and Rho-A activities, and accumulation of phosphatidyl inositol 3 (PI3) kinase products. Moreover, combined inhibition of Ras/Rho and PI3 kinase signaling by synthethic inhibitors blocked colony formation of IEC-6/Cdx1 cells in soft agar. Taken together, these results demonstrate a direct involvement of Cdx1, and its collaboration with Ras, Rho and PI3 kinase pathways, in transformation and tumorigenesis of intestinal epithelial cells.

Animals↗
PubMed2000

Expression of human immunodeficiency virus type 1 Gag protein precursor and envelope proteins from a vesicular stomatitis virus recombinant: high-level production of virus-like particles containing HIV envelope.

Recombinant vesicular stomatitis viruses have been developed as high-level expression vectors which serve as effective vaccine vectors in animals (Roberts et al., 1998, J. Virol. 72, 4704-4711; Roberts et al., 1999, J. Virol. 73, 3723-3732). Here we show that two genes can be expressed simultaneously from a single, live-attenuated VSV recombinant. The genes used encode the Pr55(gag) protein precursor of HIV-1 (1.7-kb gene) and an HIV-1 envelope (Env) protein (2.4 kb gene). Our results show that VSV can accommodate up to a 40% increase in genome size with only a threefold reduction in virus titer. Recombinants expressing the Pr55(gag) protein precursor with or without Env protein produced abundant HIV virus-like particles (VLPs) in addition to bullet-shaped VSV particles. HIV Env protein expressed from a VSV recombinant also expressing Gag was specifically incorporated into the HIV VLPs but not into the VSV particles. In contrast, VSV G protein was found in both VSV particles and in HIV VLPs. Such VSV/HIV recombinants producing HIV VLPs with Env protein could be an effective source of HIV-like particles inducing both cellular and antibody-mediated immunity to HIV-1.

AIDS Vaccines↗
PubMed1997

Identification, expression, and immunogenicity of Kaposi's sarcoma-associated herpesvirus-encoded small viral capsid antigen.

We describe a recombinant antigen for use in serologic tests for antibodies to Kaposi's sarcoma (KS)-associated herpesvirus (KSHV). The cDNA for a small viral capsid antigen (sVCA) was identified by immunoscreening of a library prepared from the BC-1 body cavity lymphoma cell line induced into KSHV lytic gene expression by sodium butyrate. The cDNA specified a 170-amino-acid peptide with homology to small viral capsid proteins encoded by the BFRF3 gene of Epstein-Barr virus and the ORF65 gene of herpesvirus saimiri. KSHV sVCA was expressed from a 0.85-kb mRNA present late in lytic KSHV replication in BC-1 cells. This transcript was sensitive to phosphonoacetic acid and phosphonoformic acid, inhibitors of herpesvirus DNA replication. KSHV sVCA expressed in mammalian cells or Escherichia coli or translated in vitro was recognized as an antigen by antisera from KS patients. Rabbit antisera raised to KSHV sVCA expressed in E. coli detected a 22-kDa protein in KSHV-infected human B cells. Overexpressed KSHV sVCA purified from E. coli and used as an antigen in immunoblot screening assay did not cross-react with EBV BFRF3. Antibodies to sVCA were present in 89% of 47 human immunodeficiency virus (HIV)-positive patients with KS, in 20% of 54 HIV-positive patients without KS, but in none of 122 other patients including children born to HIV-seropositive mothers and patients with hemophilia, autoimmune disease, or nasopharyngeal carcinoma. Low-titer antibody was detected in three sera from 28 healthy subjects. Antibodies to recombinant sVCA correlate with KS in high-risk populations. Recombinant sVCA can be used to examine the seroepidemiology of infection with KSHV in the general population.

AIDS-Related Opportunistic Infections↗
PubMed1996

Expression of additional genes in a vector derived from a minimal RNA virus.

Previous studies have shown that expression of the vesicular stomatitis virus (VSV) glycoprotein (G) from a Semliki Forest virus (SFV) RNA replicon results in the production of propagating infectious particles that we call minimal viruses. These minimal viruses consist of vesicles containing VSV G protein that bud from the plasma membrane and trap the infectious SFV G RNA, but they do not contain other viral structural proteins. The cell binding and membrane fusion activity of the VSV G protein allow minimal viruses to propagate in tissue culture cells. To determine if these minimal viruses could be used to express foreign genes, we added a second SFV promoter and a multiple cloning site downstream of the VSV G gene. We report here expression of three different proteins from this modified, minimal virus vector. Although expression of each foreign, unselected gene was lost rapidly from the vector upon passaging, it was possible after the initial transfection to derive stocks of infectious particles that could be used to infect multiple additional cultures and transfer protein expression efficiently. When cells were infected with these minimal viruses, host protein synthesis was shut off and the foreign protein and VSV G proteins were the major proteins expressed in the infected cells. Both were expressed at similar levels and accumulated to about 1-2% of total cell protein.

Animals↗
PubMed1992

Multitarget-ribozyme directed to cleave at up to nine highly conserved HIV-1 env RNA regions inhibits HIV-1 replication--potential effectiveness against most presently sequenced HIV-1 isolates.

Several mono-, di-, tetra-, penta- and nonaribozymes were developed. These multitarget-ribozymes were targeted to cleave HIV-1 env RNA at up to nine different conserved sites. Each multitarget-ribozyme consisted of a chain of up to nine hammerhead motifs, each flanked by a different targeting sequence. The multitarget-ribozymes were functional in vitro and gave rise to multiple, specific partial and/or complete RNA digestion products. Per RNA copy, multitarget-ribozymes were more efficient than monoribozymes or ribozymes targeting a subset of the same sites. In contrast to monoribozymes, a 400nt nonaribozyme, targeted to cleave at nine different sites within a 1.3kb HIV-1 env RNA substrate, was active and showed the same specificity of cleavage when it was part of a large 3.3kb transcript. We conclude that multitarget-ribozymes retain the specificity of monoribozymes, but they are more efficient per ribozyme RNA copy and they remain active when they are part of a large transcript. A tetra-, penta- or nonaribozyme under control of the SV40 late promoter, the beta-actin gene promoter or the HIV-1 LTR, respectively, were cotransfected with the infectious HIV-1 DNA clone pNL4-3 into permissive HeLa T4 cells. Each cotransfection resulted in a specific inhibition of HIV-1 replication as determined by syncytia formation and p24 antigen release. In addition, coexpression of the nonaribozyme with an HIV-1 env RNA transcript resulted in the specific dramatic reduction of the env transcript. We conclude that the multitarget-ribozymes are also functional intracellularly. A nucleotide sequence comparison of the target sites indicates that the multitarget-ribozymes could potentially be effective against all thirty HIV-1 isolates presently sequenced. Their use may help to slow the selection of viral escape mutants and thereby prolong their effectiveness. We anticipate that multitarget-ribozymes will also be more effective in the successful targeting of less variable cellular RNAs.

Base Sequence↗
PubMed1988

Are effects of antihypertensive treatment on lipoproteins merely "side-effects"? A comparison of prazosin and metoprolol.

Thirty-seven patients with a supine systolic blood pressure greater than 160 and/or a diastolic blood pressure greater than 95 mmHg were enrolled in the study and treated for 6 months with prazosin and 6 months with metoprolol (in random order). Neither the systolic nor the diastolic blood pressures differed after the two types of treatment (median difference 0/0 mmHg). The mean and median differences in serum cholesterol, however, were 0.4 and 0.3 mmol/l respectively, which were 9 and 5% of the pretreatment values. The corresponding differences in the atherogenic index (in which cholesterol in high density lipoproteins is integrated) were 10 and 8% of the pretreatment values. This difference in the metabolic response to the two drugs at the same blood pressure level is most probably of importance in the long-term prevention of ischaemic heart disease, for which high levels of serum cholesterol and atherogenic index are major risk factors.

Clinical Trials as Topic↗
PubMed1987

Decreased plasma concentrations and clinical effects of alprenolol during combined treatment with pentobarbitone in hypertension.

The antihypertensive effect of alprenolol has been studied before, during and after additional pentobarbitone treatment. The combined alprenolol-pentobarbitone treatment significantly decreased alprenolol levels by 59% and 4-hydroxyalprenolol by 24%. The effect was significant after three doses and declined over 4-5 days after pentobarbitone withdrawal. The decreased alprenolol plasma levels were associated with increased pulse rate (6%), and systolic (8%) and diastolic (9%) blood pressure. The inhibition of exercise tachycardia by alprenolol was reduced by 18% at the end of pentobarbitone treatment compared to initial monotherapy with alprenolol. The interaction is probably clinically important in those patients with hypertension and angina pectoris that are treated with barbiturates and alprenolol.

Adult↗
PubMed1987

Calcium absorption and excretion in patients treated with verapamil.

1. The effect of verapamil on the intestinal absorption of calcium was studied using a single isotope technique. Serum calcium and urinary excretion of calcium in the urine were followed in nine patients during treatment with verapamil for 2 months. 2. A dose of 80-120 mg (three times daily) resulted in a significant reduction of systolic and diastolic blood pressure. 3. There was no change in the intestinal calcium absorption (alpha) expressed as the fraction of given activity absorbed per hour (alpha = 0.82 +/- 0.19 vs alpha = 0.83 +/- 0.25; +/- s.d., NS) or of the excretion of calcium in urine (Ca/creatinine ratio 0.35 +/- 0.20 vs 0.31 +/- 0.33; NS). 4. Serum calcium was not significantly different before and during treatment (2.43 mmol l-1 +/- 0.10 vs 2.47 mmol l-1 +/- 0.14; NS). 5. This study demonstrates that verapamil, at doses recommended for clinical use, does not seem to affect the intestinal absorption of calcium, the serum calcium concentration or the excretion of calcium in urine.

Aged↗
PubMed1987

Pharmacokinetics and haemodynamic effects of felodipine as monotherapy in hypertensive patients.

The acute and steady-state pharmacokinetics and dynamics of felodipine as monotherapy have been studied in 12 hypertensive patients. Felodipine was acutely administered by a constant infusion, 1.5 mg over a 30-min period, or as a 10-mg tablet. Chronic administration was performed on a fixed dose of 10 mg b.i.d. for 28 days. The systemic availability of felodipine after the acute dose was 15%, and at steady state 12% (N.S.), with a 3-fold variation between patients. The mean plasma clearance was 0.6 L/h. The half-life measured in the 4- to 10-h interval after dose was about the same: 3.4, 3.2, and 3.3 h after the i.v. dose, the acute oral dose, and at steady state, respectively. The mean terminal half-life was 24.5 h after the oral dose at steady state. Both the intravenous and the oral doses of felodipine decreased the diastolic blood pressure for about 8 hours after dosing. The reduction in diastolic blood pressure was about 20 mmHg 1 to 2 hours after dose. Supine diastolic blood pressure was significantly reduced up to 48 h after dose at steady state. Maximum reduction of diastolic blood pressure (-22 mmHg) already occurred on the first day of treatment, while systolic blood pressure was further decreased during chronic treatment. There was a correlation between the individual maximum decrease in diastolic blood pressure after the acute oral dose with that after repeated administration (r2 = 0.70, p less than 0.01). Changes in heart rate were non-significant at steady state.

Administration, Oral↗