Search PubMed⌕ Search

Biomedical subjects

S Larsson

Publications and source records attributed to S Larsson.

At least 127 records · Page 7Linked to original sources
PubMed1997

Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal-growth-factor receptor in patients with advanced malignant glioma.

Malignant glioblastoma may over-express the epidermal-growth-factor receptor (EGF-R). Normal brain cells show a low or no expression of EGF-R. A mouse monoclonal antibody (IgG2A) (mAb 425) (EMD55900) (Merck KGaA, Bernstadt, Germany) directed against EGF-R was produced for therapeutic use. Eight patients with primary or recurrent, EGF-R-positive glioblastomas entered the study, which was designed to evaluate the clinical effect of the mAb. In order to achieve a high tumor cell saturation, the mAb was injected intratumorally twice weekly through an implantable catheter. The total administered dose varied between 4 mg and 120 mg. In 3 patients with solid tumors, a massive tumor necrosis was noted, with infiltration of macrophages, granulocytes and T cells. A further 3 patients developed clinical and radiological signs of an intense, local, inflammatory reaction. There may be a relation between the mAb dosage and the antitumor effect, insofar as higher doses seemed to cause a more pronounced, inflammatory reaction. Of the 8 patients, 6 developed human, anti-(mouse Ig) antibodies. This anti-EGF-R mAb may induce an intense, inflammatory reaction and a considerable necrosis in glioblastoma. However, the planned schedule could not be completed, even after the dose level was re-adjusted, owing to inflammatory reactions, which were severe without prior tumor debulking.

Aged↗
PubMed1997

A system for the supply of platelets suspended in a storage medium including buffy-coat-derived platelet concentrates in combination with "split" apheresis platelets.

Our objective was to create a system for the supply of platelet concentrates (PCs) based on leukocyte-filtered PCs suspended in a storage medium (PAS-II) including: (1) pooled buffy-coat-derived (BC) PCs and (2) "split" apheresis PCs. The same standards were intended for the two preparations with regard to composition and blood cell counts. In preliminary studies, similar in vitro data were found for leukocyte-filtered and non-filtered reference BC PCs. Slightly inferior in vitro results than for BC PCs restricted the shelf-life of apheresis PCs to 5 days compared to 7 days for BC PCs. With the present platelet supply system in use as a routine service for one year, the experience was very satisfactory, meeting the demands for PCs very efficiently and resulting in a low out-dating rate (5%).

Blood Platelets↗
PubMed1997

Molecular cloning and biochemical characterization of carbonic anhydrase from Populus tremula x tremuloides.

A leaf cDNA library from hybrid aspen, Populus tremula x tremuloides, was constructed. From this two different cDNA clones, denoted CA1a and CA1b, encoding a chloroplastic carbonic anhydrase (CA) were isolated and DNA sequenced. Analysis of the deduced amino acid sequences showed that the isolated CAs belong to the beta-CA family, and have identities around 70% to other dicotyledonous plant CAs. The two hybrid aspen cDNA clones display a high nucleotide sequence identity, only 12 nucleotides differ. Since only one gene copy of this soluble chloroplastic CA is present in the nuclear genome, we postulate that the two isolated cDNA clones are alleles. Northern blot hybridization revealed a CA transcript of ca. 1300 bases, 140 bases shorter than in pea. Western and northern blot hybridizations on crude protein extracts and on total RNA, respectively, isolated from stem and leaves, showed that hybrid aspen CA is expressed specifically in the leaf under the growth conditions used. Based on the deduced amino acid sequence, the mature hybrid aspen CA enzyme subunit has a molecular mass of 24.8 kDa. The enzyme was over-expressed in Escherichia coli, and purified by affinity chromatography. Biochemical characterization showed that the protein structure and the CO2-hydration activity are similar to the pea enzyme. Molecular characterization of a CA from a perennial plant has not previously been performed, and it demonstrates that both the structure and activity of hybrid aspen CA resembles CAs from annual plants.

Amino Acid Sequence↗
PubMed1997

Toward a theory of social pharmacology: the actor-spectator paradox applied to the psychotropic prescribing process.

Traditionally, drug prescribing was regarded as part of the physician's decision-making role. However, recently it has been recognized that such a perspective is insufficient to understand the psychotropic prescribing process. To understand this process, a drug communication perspective is necessary. This article describes the actor-spectator paradox and its influence on drug communication and psychotropic drug prescribing. The actor-spectator paradox postulates that the actor and the spectator have divergent perspectives about the cause of the actor's behavior. The spectator makes assumptions about the actor's cognitive system other than the actor herself is making. This difference is often the basis for misunderstandings between a health professional and a patient. If a health professional can learn to make more realistic assumptions about a patient's cognitive system, communication between the two will improve. In the same way a patient has to learn to make more realistic assumptions about the cognitive systems of health professionals. The actor-spectator paradox can be applied to different areas of Social Pharmacology such as the diagnosis of patients suffering from mental health problems, drug compliance, informed consent, and the prescribing of psychotropics.

Decision Making↗
PubMed1996

A novel ribozyme target site located in the HIV-1 nef open reading frame.

We have tested the sequence UUC CAG UCA GAC CU, at position 9016--9029 within the HIV-1(SF2) nef open reading frame, for accessibility to antisense and hammerhead ribozyme attack. The accessibility was first studied using a phosphorothioate-modified 14-nt DNA oligo (complementary to the nef9016--9029 site). A dose-dependent repression of HIV-1(SF2) growth was observed in human peripheral blood mononuclear cells after exogenous administration of the oligo to the cell culture medium. A hammerhead ribozyme with a 6+7-nt antisense specificity for the nef9016--9029 site (hhRz.nef9016--9029) was constructed and transfected into the human T-cell line HUT78. Again, a dose-dependent repression of virus growth was observed when different individual clones expressing hhRz.nef9016--9029 were infected with HIV-1(SF2). A complete abrogation of virus production was observed after infection with a low (0.5 TCID50) HIV-1 titer. Increasing doses (2.5 and 12.5 TCID50) of HIV-1 virus yielded a low production (10(3)-fold reduced) of virus particles in most cases; but a complete, or close to complete, abrogation was observed even in individual cultures infected with the highest dose. Presence of proviral pol and gag sequences in hhRz.nef9016--9029-expressing HUT78 clones was assayed, using PCR. Interestingly, since no pol and gag PCR products could be detected, the results strongly indicated that the hammerhead ribozyme was already acting on the infecting HIV RNA before its reverse transcription and integration as proviral DNA. In summary, the results obtained in this study support the nef9016--9029 site as a strong new candidate for ribozymal gene therapy against HIV-1 infection.

Base Sequence↗
PubMed1996

Cytomegalovirus-induced CD13-specific autoimmunity--a possible cause of chronic graft-vs-host disease.

Cytomegalovirus (CMV) infection has been suggested to be associated with certain autoimmune phenomena as well as with the development of chronic graft-versus-host disease (cGVHD) following allogeneic bone marrow transplantation. Earlier we found that the CMV-associated host protein CD13 is immunogenic during CMV infection in allogeneic bone marrow transplant patients, resulting in production of CD13-specific antibodies (7). Here we found a close correlation between CD13-specific immunity and later development of cGVHD in 26 of 33 patients who could be evaluated for this disease. Of seven patients with CMV disease, six developed extensive cGVHD, all of whom had CD13 specific antibodies (P=0.0002). All 14 patients who were CD13-immune later developed either limited or extensive cGVHD (P=0.0008). Antibodies in sera from the CD13-immune patients suffering from cGVHD recognized normal structures in cryosectioned skin biopsies from control individuals, producing a staining pattern similar to that of CD13-specific monoclonal antibodies. The antibody binding could be specifically blocked by preincubation of the skin sections with a mixture of monoclonal antibodies against CD13, and was also abolished after preabsorption of sera to mouse cells expressing human CD13. No other common autoantibodies were identified in more than single patients. Furthermore, in vivo binding of IgM antibodies in a CD13-like fashion was preferentially demonstrated in skin and oral mucosa biopsies from the CD13-immune patients suffering from cGVHD. Thus, we suggest that CMV-induced CD13-specific autoimmunity contribute to tissue damage in chronic graft-versus-host reactions.

3T3 Cells↗
PubMed1996

Social consequences of insulin-dependent diabetes mellitus are limited: a population-based comparison of young adult patients vs healthy controls.

In a population-based study, the social situation of 91 young adult patients with Type 1 diabetes mellitus (IDDM) since childhood was compared to that of an age- and sex-matched group of 189 healthy persons. Their mean age was 37.2 years, duration of diabetes 28.7 years and severe complications were present in 13 of the 91 patients. A nearly 10-fold increased mortality rate was found in diabetic patients, mainly due to diabetic nephropathy and trauma, including suicide. The employment rate was lower in diabetic patients (71% vs 85%, p < 0.05); the need for welfare benefits was greater (15% vs 3%, p < 0.01). These differences were mainly the consequence of diabetic late complications. Education, housing conditions, life style, civil state, alcohol and smoking habits were similar in both groups. Confidence in the future was slightly less in diabetic patients (p < 0.05). In conclusion, besides an increased mortality rate, the present study has shown no serious social consequences in adult Type 1 diabetic patients without severe late complications, as compared to matched controls. Our results indicate that IDDM affects social life only to a limited extent, in the absence of severe vascular complications.

Adult↗
PubMed1996

The influence of seat-back and head-restraint properties on the head-neck motion during rear-impact.

The influence of different seat properties on the head-neck motion during a low-velocity rear-end impact was tested using a Hybrid III-dummy fitted with a modified neck (RID-neck). The results show that by modifying the properties of the seat-back and head-restraint it is possible to influence the head-neck kinematics to a great extent. It was possible to virtually eliminate the neck extension motion during a rear-impact. This will hopefully result in a significant decrease in neck injury risk in real world rear-impacts.

Acceleration↗
PubMed1996

Development of 123I-labelled NNC 13-8241 as a radioligand for SPECT visualization of benzodiazepine receptor binding.

[125I]- and [123I]NNC 13-8241 were prepared from the trimethyltin precursor and radioactive iodide using the chloramine-T method. The total radiochemical yields of [125I]- and [123I]NNC 13-8241 were 60-70% and 40-50% respectively, with radiochemical purity higher than 98%. In binding studies with [125I]NNC 13-8241 in rats in vitro and in vivo a high uptake of radioactivity was demonstrated in brain regions known to have a high density of benzodiazepine (BZ) receptors such as the occipital and frontal cortex. SPECT examination with [123I]NNC 13-8241 in a Cynomolgus monkey demonstrated a high uptake of radioactivity in the occipital and frontal cortex. After displacement with flumazenil radioactivity in these brain regions was reduced to the level of a central region including the pons. Four hours after injection about 80% of the radioactivity in monkey plasma represented unchanged radioligand. This low degree of metabolism indicates that NNC 13-8241 is metabolically more stable than the radioligands hitherto developed for imaging of BZ-receptors in the primate brain.

Animals↗
PubMed1996

Electron paramagnetic resonance studies of the soluble CuA protein from the cytochrome ba3 of Thermus thermophilus.

The electron paramagnetic resonance (EPR) spectrum of the binuclear CuA center in the water-soluble subunit II fragment from cytochrome ba3 of Thermus thermophilus was recorded at 3.93, 9.45, and 34.03 GHz, and the EPR parameters were determined by computer simulations. The frequency and M1 dependence of the linewidth was discussed in terms of g strain superimposed on a correlation between the A and g values. The g values were found to be gx = 1.996, gy = 2.011, gz = 2.187, and the two Cu ions contribute nearly equally to the hyperfine structure, with magnitude of Ax magnitude of approximately 15 G, magnitude of Ay magnitude = 29 G, and magnitude of Az magnitude of = 28.5 G (65Cu). Theoretical CNDO/S calculations, based on the x-ray structure of the Paracoccus denitrificans enzyme, yield a singly occupied antibonding orbital in which each Cu is pi*-bonded to one S and sigma*-bonded to the other. In contrast to the equal spin distribution suggested by the EPR simulations, the calculated contributions from the Cu ions differ by a factor of 2. However, only small changes in the ligand geometry are needed to reproduce the experimental results.

Bacterial Proteins↗
PubMed1996

Magnetic resonance imaging in the follow-up of patients after aortic root reconstruction.

Long-term survival after replacement of the aortic root with a composite graft is improving. Late deaths are in several cases due to complications related to the previous surgery or to pathologies of the remaining aorta. Regular follow-up of these patients is of paramount importance. The purpose of this study is to evaluate the reliability of magnetic resonance imaging (MRI) in such cases. Twenty-seven patients (9 dissections and 18 aneurysms) who had undergone replacement of the aortic root with a composite graft were studied 20 to 167 months after surgery using magnetic resonance imaging with a 1.5 Tesla magnet. The left-ventricular outflow tract, the mechanical valve function, the proximal part of the coronary arteries, the graft, and the remaining aorta could be examined. No aortic insufficiency, ectasy of the proximal part of the coronaries, or pseudoaneurysms were seen. A widening of the remaining ascending aorta was noted in 4 cases. A still open, dissected pipe was visualized in 7 patients. Our conclusions are that MRI provides excellent images of the thoracic and abdominal aorta following surgical repair. The examination is becoming cost-competitive. More import is its very low risk for the patient group considered here: since it is non-invasive and requires no contrast medium or X-ray exposure, examinations can be repeated as required.

Aortic Dissection↗
PubMed1996

Endemicity and clinical picture of liver disease due to obstruction of the hepatic portion of the inferior vena cava in Nepal.

Obstructive lesion of the hepatic portion of the inferior vena cava is common in Nepal. The clinical data on 150 patients who were seen at the Liver Unit, Bir Hospital, Kathmandu, in three years from 1990 to 1992 were analysed. Although the majority of patients were over 20 years of age, 25 patients were below 10 years of age; there were more males than females in this study. This disease accounted for 17% of 866 patients with chronic liver disease and for nearly one quarter of 267 biopsies performed on this patient group during the same period. Obstructive lesions of the inferior vena cava seem to be more common among poor people with malnutrition. Clinically, our patient group could be divided into acute (n = 27), subacute (n = 43) and chronic (n = 80) cases. The important clinical features are hepatomegaly and/or ascites and, in chronic cases, prominent dilated superficial veins over the body trunk with cephalad flow. Ultrasound is the most helpful diagnostic procedure, especially in subacute and chronic cases, as it frequently demonstrates caval obstruction, thrombosis, dilated hepatic veins and intrahepatic collaterals. Diagnosis is confirmed by cavography, which shows a caval obstruction of varying lengths at the cavo-atrial junction or a marked narrowing of the hepatic portion of the vena cava. In subacute and chronic cases cavography also demonstrates collateral veins, such as the ascending lumbar, hemiazygos and azygos that drain into the superior vena cava. Chronic cases had periods of exacerbation often associated with bacterial infection. The aetiology of inferior vena cava obstruction at its hepatic portion is not known, but there seems to be a frequent association of bacterial infection with the disease.

Acute Disease↗
PubMed1996

A novel mechanism for virus-induced autoimmunity in humans.

A novel mechanism for virus-induced autoimmunity in humans is described. Infection of immunocompromised bone marrow-transplanted patients with human CMV results in the formation of autoantibodies specific for the cell-surface protein CD13 (aminopeptidase N). CD13 is present on all CMV-susceptible cells and infection can be specifically blocked by antibodies against CD13. CMV particles carry CD13, which is incorporated in the viral envelope during budding of viral nucleo-capsids into Golgi-derived vacuoles. Antibodies against CD13 are virus-neutralizing, in efficiency comparable to antibodies against viral envelope glycoproteins. Autoantibodies against CD13 are present in patients who develop chronic GVHD following allogeneic bone marrow transplantation. This lesion shows striking similarities to certain autoimmune diseases in humans, of which scleroderma is one example. In vivo binding of antibodies to tissue structures known to be targets for chronic GVHD has been demonstrated in patients with chronic GVHD. Finally, patient serum containing CD13-specific antibodies binds to skin and mucosa tissue sections in vitro, a binding which is inhibited by CD13-specific monoclonal antibodies. Thus a virus infection can activate an immune response against a specific autoantigen, providing possibilities for destruction of non-infected host cells, as originally proposed by Fujinami & Oldstone (1985), and also for the molecular mimicry model for induction of autoimmunity. Our findings lend support to the idea that inhibiting the transfer of CMV infection in bone marrow transplants will reduce morbidity and mortality from CMV infection but will also reduce the incidence of chronic GVHD. Elimination of CD13+ cells in bone marrow is not believed to interfere with the chance of recipient repopulation, and may be a way to decrease morbidity and mortality substantially following BMT. For all patients, every effort should be taken to prevent a post-BMT CMV infection in order to reduce the risk of the later development of chronic GVHD.

Animals↗
PubMed1996

Functional status and well being in chronic obstructive pulmonary disease with regard to clinical parameters and smoking: a descriptive and comparative study.

BACKGROUND: Self-assessment questionnaires which measure the functional and affective consequences of chronic obstructive pulmonary disease (COPD) give valuable information about the effects of the disease and may serve as important tools with which to evaluate treatment. METHODS: A cross sectional comparative study was performed between patients with COPD (n = 68), stratified according to pulmonary function, and a healthy control group (n = 89). A battery of well established clinical and quality of life measures (the Sickness Impact Profile (SIP), Mood Adjective Check List (MACL), and Hospital Anxiety and Depression scale (HAD)) was used to examine in which functional and affective aspects the patient group differed from the control group and how these measures related to pulmonary function and smoking habits. RESULTS: Compared with the controls, COPD affected functional status in most areas, not just those requiring physical activity. Forty six patients with forced expiratory volume in one second (FEV1) below 50% predicted showed particularly high levels of dysfunction in ambulation, eating, home management, and recreation/ pastimes (SIP). Despite this, their level of psychosocial functioning and mood status was little different from that of the healthy controls. Among the patients, a subgroup reported substantial psychological distress, but mood status was only weakly, or not at all, related to pulmonary function. Smoking habits did not affect functional status or well being. CONCLUSIONS: Quality of life is not significantly affected in patients with mild to moderate loss of pulmonary function, possibly due to coping and/or pulmonary reserve capacity. This suggests that generic self-assessment questionnaires are of limited value for detecting the early consequences of COPD. However, in later stages of the disease they are sensitive enough to discriminate between patients with different levels of pulmonary dysfunction. The low correlations between the indices of pulmonary function and the indices of affective status suggest that well being depends, to a large extent, on factors outside the clinical domain.

Affect↗
PubMed1996

Factors influencing haemostasis and blood transfusion in cardiac surgery.

To find out the risk factors influencing perioperative bleeding and use of blood products in cardiac surgery so that appropriate interventions can be selected for blood conservation, risk factors were analysed in 343 cardiac surgical patients, retrospectively, by multiple regression technique. The results showed that the factors related to postoperative bleeding were male gender, Higgins score, cardiopulmonary bypass (CPB) time, operation procedures, intraoperative blood loss and use of internal mammary artery (IMA) graft. Factors related to perioperative homologous blood transfusions were emergency surgery, preoperative haemoglobin level, Higgins score, intraoperative blood loss, operation time and operation procedures. The geometric mean of postoperative bleeding in the entire series was 1085 ml and the mean packed red cell, plasma and platelet transfusions were 3.29 +/- 0.4, 1.96 +/- 0.39 and 0.21 +/- 0.05 units respectively. The incidence of homologous blood transfusion during the hospital stay was 58.9% for the entire series and 54.5% in the nonrevision patients. Emergency patients received significantly more blood transfusion (p = 0.0001). Perioperative blood loss and transfusions are still problems in cardiac surgery and certain patient groups in this study were identified as high risk; available blood conservation techniques, therefore, are recommended in these patients.

Blood Transfusion↗
PubMed1996

Bronchial brush biopsies for studies of epithelial inflammation in stable asthma and nonobstructive chronic bronchitis.

Recently, bronchial brush biopsy (BBB) has been introduced as a complimentary method to bronchial forceps biopsy for the study of bronchial epithelial cells. We wanted to determine whether epithelial inflammatory cells in bronchial brush biopsies can reflect mucosal inflammation assessed indirectly by levels of cellular activation markers in bronchial lavage fluid. We studied 15 healthy controls, 11 asthmatics with regular steroid inhalation therapy, 13 asthmatics without steroids, and 10 smokers with nonobstructive chronic bronchitis. Differential counts of epithelial and inflammatory cells were made from the BBB material. Bronchial lavage levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, hyaluronan and interleukin-8 (IL-8) were measured as indirect markers for inflammatory cell activation. We found an increased percentage of eosinophil granulocytes in the BBB from the steroid-untreated asthmatic patients (1.16%) in comparison to the other groups (0.11%, 0.09% and 0.02%, respectively; p<0.01). In the steroid-untreated asthmatic patients, the percentage of eosinophils correlated with ECP in bronchial lavage fluid (r=0.73; p<0.01), indicating that the BBB method can reflect the degree of eosinophilic activation. A negative correlation was found for the percentage of eosinophils in BBB with levels of provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) for the asthmatic patients in the study (r= -0.67; p<0.003). The bronchial brush biopsy method appears to give information on the changes present in superficial bronchial epithelium in inflammatory airways disease. These changes appear to relate to the degree of inflammatory activity and disease severity in asthma.

Administration, Inhalation↗