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Biomedical subjects

P Albertsson

Publications and source records attributed to P Albertsson.

At least 19 recordsLinked to original sources
PubMed2006

Composition of coronary plaques obtained by directional atherectomy in stable angina: its relation to serum lipids and statin treatment.

OBJECTIVES: The stability and inflammatory activity in atherosclerotic plaques may be modulated by lipids and lipoproteins as well as the pleiotropic effects of statins. The aim of this study was to analyse the effect of statin treatment as well as the relation of plasma lipids and lipoproteins to tissue composition in atherosclerotic plaques. DESIGN: Patients with stable angina and coronary plaques suitable for directional coronary atherectomy (DCA) were randomized to atorvastatin (80 mg once daily) or placebo (29 randomized, 22 underwent DCA, 11/group). After an average treatment of 10 weeks, patients underwent DCA, tissue specimens were obtained, and the tissue composition was determined by immunohistochemistry. RESULTS: Atorvastatin reduced the T-cell content, but did not change lipid, collagen, smooth muscle cell, or macrophage content. Plasma levels of apolipoprotein AI (apoAI) correlated positively with tissue collagen and inversely with metalloproteinase-9 and macrophage content. About half the specimens contained neutrophil granulocytes. CONCLUSIONS: Short-term atorvastatin treatment tended to reduce the T-cell content of atherosclerotic plaques, indicating modulation of cell-mediated immunity. High plasma levels of apoAI correlated with increased collagen content and reduced inflammation, supporting the notion that plasma apoAI stabilizes atherosclerotic plaques. The significance of neutrophils in the lesions merits further study.

Adult↗
PubMed2006

High dose-rate brachytherapy of prostate cancer utilising Iridium-192 after-loading technique: technical and methodological aspects.

The aim of this study was to focus on certain characteristic problems associated with Iridium-192 high dose-rate brachytherapy (Ir-192 HDR-BT) in combination with external beam radiation therapy (EBRT) in the treatment of patients with localised prostate cancer. Over a period of 16 years, >2,000 patients with prostate cancer have been treated in Sweden with a combination of two fractions of 10 Gy Ir-192 HDR-BT and 50 Gy of fractionated EBRT. Although this treatment is usually well tolerated, there are biological and technical factors to be considered before and during the treatment of the patient to avoid side effects or under-treatment of the target volume. Some of the problems facing the doctors are transducer stability, needle deviation, target definition, target motion, pubic arch interference, concomitant diseases and tolerance doses for different organs at risk. These problems are discussed and possible solutions are presented in this study.

Brachytherapy↗
PubMed2005

Morphological appearance, content of extracellular matrix and vascular density of lung metastases predicts permissiveness to infiltration by adoptively transferred natural killer and T cells.

We have recently shown that adoptively transferred, IL-2-activated natural killer (A-NK) cells are able to eliminate well-established B16-F10.P1 melanoma lung metastases. However, some B16-F10.P1 lung metastases were resistant to infiltration by the A-NK cells and also resistant to the A-NK cell treatment. The infiltration-resistant (I-R) B16-F10.P1 metastases had a unique "compact" morphology compared to the "loose" morphology of the infiltration-permissive (I-P) metastases. Here, we show that I-P loose tumors and I-R compact tumors are also found in lung metastases of mouse Lewis lung carcinoma (3LL), MCA-102 sarcoma, and MC38 colon carcinoma as well as rat MADB106 mammary carcinoma origin. Furthermore, the infiltration resistance of the compact tumors is not restricted to A-NK cells, since PHA and IL-2 stimulated CD8+ T-cells (T-LAK cells) also infiltrated the compact tumors poorly. Analyses of tumors for extracellular matrix (ECM) components and PECAM-1(+) vasculature, revealed that the I-R lesions are hypovascularized and contain very little laminin, collagen and fibronectin. In contrast, the I-P loose tumors are well-vascularized and they contain high amounts of ECM components. Interestingly, the distribution pattern of ECM components in the I-P loose tumors is almost identical to that of the normal lung tissue, indicating that these tumors develop around the alveolar walls which provide the loose tumors with both a supporting tissue and a rich blood supply. In conclusion, tumor infiltration by activated NK and T cells correlates with the presence of ECM components and PECAM-1(+) vasculature in the malignant tissue. Thus, analysis of the distribution of ECM and vasculature in tumor biopsies may help select patients most likely to benefit from cellular adoptive immunotherapy.

Adoptive Transfer↗
PubMed2001

Stenting in small coronary arteries (SISCA) trial. A randomized comparison between balloon angioplasty and the heparin-coated beStent.

OBJECTIVES: The purpose of this study was to assess the clinical and angiographic benefits of elective stenting in coronary arteries with a reference diameter of 2.1 to 3.0 mm, as compared with traditional percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: The problems related to small-vessel stenting might be overcome using modern stents designed for small vessels, combined with effective antiplatelet therapy. METHODS: In five centers, 145 patients with stable or unstable angina were randomly assigned to elective stenting treatment with the heparin (Hepamed)-coated beStent or PTCA. Control angiography was performed after six months. The primary end point was the minimal lumen diameter (MLD) at follow-up. Secondary end points were the restenosis rate, event-free survival and angina status. RESULTS: At follow-up, there was a trend toward a larger MLD in the stent group (1.69 +/- 0.52 mm vs. 1.57 +/- 0.44 mm, p = 0.096). Event-free survival at follow-up was significantly higher in the stent group: 90.5% vs. 76.1% (p = 0.016). The restenosis rate was low in both groups (9.7% and 18.8% in the stent and PTCA groups, respectively; p = 0.15). Analyzed as treated, both the MLD and restenosis rate were significantly improved in patients who had stents as compared with PTCA. CONCLUSIONS: In small coronary arteries, both PTCA and elective stenting are associated with good clinical and angiographic outcomes after six months. Compared with PTCA, elective treatment with the heparin-coated beStent improves the clinical outcome; however, there was only a nonsignificant trend toward angiographic improvement.

Angioplasty, Balloon, Coronary↗
PubMed2001

Continued benefit of coronary stenting versus balloon angioplasty: five-year clinical follow-up of Benestent-I trial.

OBJECTIVES: This study sought to establish whether the early favorable results in the Benestent-I randomized trial comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in 516 patients with stable angina pectoris are maintained at 5 years. BACKGROUND: The size of the required sample was based on a 40% reduction in clinical events in the stent group. Seven months and one-year follow-up in this trial showed a decreased incidence of restenosis and clinical events in patients randomized to stent implantation. METHODS: Data at five years were collected by outpatient visit, via telephone and via the referring cardiologist. Three patients in the stent group and one in the percutaneous transluminal coronary angioplasty (PTCA) group were lost to follow-up at five years. Major clinical events, anginal status and use of cardiac medication were recorded according to the intention to treat principle. RESULTS: No significant differences were found in anginal status and use of cardiac medication between the two groups. In the PTCA group, 27.3% of patients underwent target lesion revascularization (TLR) versus 17.2% of patients in the stent group (p = 0.008). No significant differences in mortality (5.9% vs. 3.1%), cerebrovascular accident (0.8% vs. 1.2%), myocardial infarction (9.4% vs. 6.3%) or coronary bypass surgery (11.7% vs. 9.8%) were found between the stent and PTCA groups, respectively. At five years, the event-free survival rate (59.8% vs. 65.6%; p = 0.20) between the stent and PTCA groups no longer achieved statistical significance. CONCLUSIONS: The original 10% absolute difference in TLR in favor of the stent group has remained unchanged at five years, emphasizing the long-term stability of the stented target site.

Angina Pectoris↗
PubMed2001

A quantitative model of the domain structure of the photosynthetic membrane.

A model is presented that gives a quantitative picture of the distribution of the photosynthetic components in the photosynthetic membrane of higher plants. A salient feature of the model is that most of the pigments are located in the grana where photosystem I and II carry out linear electron transport, whereas the stroma lamellae, which harbour <20% of the pigments, carry out photosystem-I-mediated cyclic electron transport. This arrangement derives from the observation that more pigments are associated with photosystem I, which therefore captures more quanta than photosystem II. The excess pigments associated with photosystem I are thought to be located in the stroma lamellae.

Chloroplasts↗
PubMed2001

The phenotypic heterogeneity of human natural killer cells: presence of at least 48 different subsets in the peripheral blood.

Peripheral blood natural killer (NK) cells are usually defined as a homogeneous cell population. However, NK cells show heterogeneous expression of a diversity of cell surface molecules, which might reflect the diversity of NK-cell functions. Therefore, a more specific phenotypic definition of NK cells is necessary. In this study, we made an inventory of phenotypic subsets that are present within the peripheral blood NK-cell population of healthy donors based on differential expression of nine cell-surface markers. Using three-colour flow cytometric analysis we were able to define at least 48 different CD56(+) NK-cell subsets within the peripheral blood. This phenotypic heterogeneity appeared to be stable among healthy individuals, and was also steady within CD56(dim) and CD56(bright) NK populations, indicating a possible role for these subsets in NK-cell function or differentiation.

Adult↗
PubMed2001

Characterization of Forssman and other antigen/antibody systems in vascularized mouse heart to rat xenotransplantation.

In the present study, the nature of hyperacute xenograft rejection was closely studied in a vascularized mouse-to-rat transplantation model. Antibodies against mouse heart, erythrocytes and lymphocytes and against the Forssman antigen were raised in the rat. Upon heterotopic heart transplantation the respective antisera were intravenously (i.v.) injected. Passive transfer of antiheart, antierythrocyte or antilymphocyte serum resulted in hyperacute rejection of the transplanted mouse heart. Subfractionation of the antiheart serum showed that the capacity to induce hyperacute rejection was carried by the immunoglobulin (Ig)G fraction. When antierythrocyte serum adsorbed with mouse erythrocytes was administered the cardiac grafts remained beating. To the contrary, antilymphocyte serum adsorbed with erythrocytes still had the capacity to induce hyperacute rejection. None of the rats that had previously been challenged with the Forssman antigen rejected their grafts hyperacutely. Subsequent investigations by electron microscopy revealed that the Forssman antigen is expressed on dendritic cells (DC) adjacent to the vessels, but not on the vascular endothelium, thus explaining the inability of the anti-Forssman serum to induce hyperacute rejection. Taken together, we have demonstrated the existence of several xenoantigens that can be targets for antibody-mediated rejection, suggesting that more than one relevant xenoantigen exists also in more distantly related combinations, such as the pig-to-human combination.

Acute Disease↗
PubMed2001

Physical activity, symptoms of chest pain and dyspnea in patients with ischemic heart disease in relation to age before and two years after coronary artery bypass grafting.

BACKGROUND: To describe limitation of physical activity, cause of limitation of physical activity and symptoms of dyspnea and chest pain in relation to age before and 2 years after coronary artery bypass grafting (CABG). METHODS: All patients from Western Sweden who underwent CABG without concomitant procedures during 3 years in 1989-1991 answered questionnaires before, and 2 years after the operation. Patients were divided into 3 age groups of equal size i.e. 32-59 years, 60-67 years and > or = 68 years. RESULTS: In total, 2121 patients participated in the evaluation. The overall 2 year mortality in the 3 age groups was 3.8%, 6.8% and 12.2% (p<0.001). Limitation of physical activity was significantly associated with age prior to surgery but not thereafter. Improvement in physical activity, following CABG, was significant in all age groups. The proportion of patients being free of dyspnea increased markedly regardless of age. The number of chest pain attacks was associated with age after CABG, i.e. fewer attacks in the elderly, but such an association was not found prior to surgery. Improvement in number of chest pain attacks was more marked in the elderly. CONCLUSIONS: Physical activity improved similarly in all age groups after CABG. Attacks of chest pain, although significantly reduced in all age groups, seemed more effectively reduced in the elderly.

Adult↗
PubMed2000

Secreted and membrane-associated matrix metalloproteinases of IL-2-activated NK cells and their inhibitors.

We have previously documented that rat IL-2-activated NK (A-NK) cells produce matrix metalloproteinase-2 (MMP-2) and MMP-9. In this study, we describe mouse A-NK cell-derived MMPs, including MT-MMPs, and also TIMPs. RT-PCR analysis from cDNA of mouse A-NK cells revealed mRNA for MMP-2, MMP-9, MMP-11, MMP-13, MT1-MMP, MT2-MMP, TIMP-1, and TIMP-2. MMP-2 and MMP-9 expression was confirmed by gelatin zymography. Moreover, we report for the first time that MT-MMPs are expressed by NK cells, i.e., large granular lymphocytes as determined by both RT-PCR and Western blots. TIMP-1 expression was detected as a 29-kDa protein in Western blots. It is intriguing that TIMP-2 protein from A-NK cells was also detected as a 29-kDa protein, which is clearly different from the previously reported molecular mass of 21 kDa in mouse and human cells. In addition, inhibition of MMPs by BB-94, a selective inhibitor of MMP, significantly inhibited the ability of mouse A-NK cells to migrate through Matrigel, a model basement membrane. Taken together, these findings suggest that A-NK cells may therefore use multiple MMPs in various cellular functions, including degradation of various extracellular matrix molecules as they extravasate from blood vessels and accumulate within cancer metastases following their adoptive transfer.

Animals↗
PubMed2000

2B4 stimulation of YT cells induces natural killer cell cytolytic function and invasiveness.

2B4 is a surface molecule found on all human natural killer (NK) cells, a subset of CD8+ T cells, monocytes and basophils. It was originally identified on mouse NK cells and the subset of T cells that mediate non-major histocompatibility complex (MHC)-restricted killing. Recently,9 we have cloned the human homologue of 2B4 (h2B4) and found h2B4 to also mediate non-MHC-restricted cytotoxicity. In this study, we examine h2B4 in regulating various functions of NK cells using a human NK cell line YT, with monoclonal antibody (mAb) C1.7, an antibody that specifically recognizes h2B4. Ligation of surface 2B4 with mAb C1.7 increases YT's ability to destroy tumour cells. In the presence of mAb C1.7, the production of interferon-gamma (IFN-gamma) by YT cells is greatly enhanced. Engagement of surface 2B4 by mAb C1.7 downregulates the expression of h2B4 at the cell surface as well as the expression of h2B4 mRNA. Also, signalling through h2B4 causes the increased expression of matrix metalloproteinase-2, a member of the matrix degrading proteinase family. Thus, in addition to modulating cytolytic function and cytokine production of NK cells, activation through surface 2B4 may play a role in upregulating the machinery for degradation of extracellular matrices to promote invasion of the tumour by NK cells.

Animals↗
PubMed1999

Comparison of diabetic and non-diabetic patients referred for coronary angiography.

AIM: To evaluate whether diabetic patients differ from non-diabetic patients when referred for coronary angiography regarding previous history, indication for and findings at coronary angiography, use of medication, exercise test results and mortality. METHODS: Data were prospectively collected on patients referred for consideration of coronary revascularization to seven of the eight public Swedish heart centers that performed approximately 92% of all bypass operations in Sweden in 1994. RESULTS: 2762 patients were included of whom 406 (15%) had a history of diabetes mellitus. There was no difference in age or sex in the two groups. Chronic stable angina was the most common indication (73% in both groups) and only 3% were admitted due to silent ischemia. Diabetic patients had more severe symptoms (Canadian Cardiovascular Society III-IV) than non-diabetic patients (66% vs. 58%, p<0.01). They more frequently used ACE-inhibitors (33% vs. 19%, p<0.0001) and calcium channel blockers (47% vs. 40%, p<0.01) and more often had a diagnosis of arterial hypertension than non-diabetic patients (50% vs. 33%, p<0.0001). Diabetic patients more often had depressed myocardial function (EF<35%); 12% and 8%, respectively (p<0.01), and more extensive coronary artery disease (left main/3-VD; 48% vs. 37%, p<0.001). The mortality during the subsequent 21 months was 7.9% among diabetic patients and 3.6% among non-diabetic patients (p<0.001). CONCLUSION: Among patients being referred for coronary angiography in Sweden, 15% were patients with a history of diabetes. They differed from patients without such a history by more often having severe symptoms and a higher prevalence of left main/triple vessel disease. Coronary angiography may thus be underused in diabetic patients with chest pain.

Adult↗
PubMed1999

Continuous vectorcardiographic monitoring of ischemia during coronary angioplasty in patients with bundle-branch block.

BACKGROUND: Patients with the combination of bundle-branch block and ischemic heart disease have a poor outcome. There is no established criterion for detection of transient ischemia when bundle-branch block is present. OBJECTIVE: To elucidate vectorcardiographic changes during coronary angioplasty of patients with bundle-branch block. DESIGN AND METHODS: The QRS complex and ST-segment changes of 29 patients with bundle-branch block were studied during elective coronary angioplasty using continuous vectorcardiography. Data for the patients with bundle-branch block were compared with data for narrow-QRS-complex controls, matched for the vessel dilated, sex, and age. RESULTS: Patients with bundle-branch block were found to have more pronounced changes in the QRS-vector difference as a response to coronary occlusion than did controls. ST-vector magnitude responded in a similar way during coronary occlusion of patients with and without bundle-branch block but from different baselines. ST change-vector magnitude was found to be the most sensitive parameter for detection of ischemia in patients with bundle-branch block as well as for controls. CONCLUSION: Monitoring of transient ischemia during coronary angioplasty for patients with bundle-branch block is feasible using continuous vectorcardiography. A change in ST vector magnitude > 100 microV is suggested to indicate significant ischemia in the presence of bundle-branch block.

Aged↗
PubMed1998

Esophageal dysfunction in syndrome X.

Syndrome X is defined as anginal chest pain accompanied by objective signs of ischemia on exercise testing or myocardial scintigraphy, but with angiographically "normal" coronary arteries. The etiology of this enticing syndrome is still not known. Besides myocardial ischemia, esophageal dysfunction and visceral hypersensitivity may play a role in the development of pain. The purpose of this study was to study esophageal function and visceral sensitivity in patients with syndrome X. Twenty consecutive patients with the diagnosis of syndrome X were investigated with esophageal manometry and a 24-hour pH recording. Visceral esophageal sensitivity was explored by balloon distention of the distal esophagus, as well as by instillation of acid. Twelve patients (67% of the 18 evaluated) had some abnormality on 24-hour pH monitoring; 2 had abnormal global acid exposure time (pH <4) and 7 had symptoms coincidental with episodes of pH <4. Seven patients (35%) had esophageal dysmotility including 5 with the "nutcracker" esophagus. Esophageal hypersensitivity to acid (n = 9) or distention (n = 13) was seen in 14 of the 20 patients. Eleven patients received acid suppressive therapy that resulted in amelioration of chest pain in 8 (73%). Thus, results suggest that esophageal hypersensitivity rather than gross functional abnormality is an important factor for the development of chest pain in patients with syndrome X, and that acid in the context of a hypersensitive esophagus is the main culprit. Acid suppression may ameliorate pain in a substantial proportion of patients.

Adult↗
PubMed1998

Matrix metalloproteinases produced by rat IL-2-activated NK cells.

We have previously documented that adoptively transferred IL-2-activated NK (A-NK) cells can accumulate within cancer metastases. Electron microscopic studies of pulmonary metastases have revealed that adoptively transferred A-NK cells that accumulate within metastases bind to endothelial cells and are able to traverse basement membranes. We have now extended these morphologic studies. We report that rat A-NK cells produce two matrix metalloproteinases: MMP-2 and MMP-9, as determined by SDS-PAGE gelatin zymography. These activities are inhibited following incubation with BB-94 (batimastat), a specific inhibitor of matrix metalloproteinases but not with 3,4-dichloroisocoumarin, an inhibitor of neutral serine proteases. The identity of MMP-2 was confirmed by Western blots using a polyclonal Ab against human MMP-2, whereas reverse transcriptase-PCR analysis of mRNA extracts of A-NK cells has confirmed the presence of MMP-9. In addition, we report for the first time that A-NK cells can migrate through a model basement membrane-like extracellular matrix. Moreover, the ability of A-NK cells to migrate through this model basement membrane was partially inhibited by BB-94; however, BB-94 has no effect on A-NK cell-mediated cytotoxicity, suggesting that matrix metalloproteinases do not contribute to cytolytic function of A-NK cells. In sum, our studies show that A-NK cells employ BB-94-inhibitable matrix metalloproteinases to degrade extracellular matrices. This suggests that matrix metalloproteinases may play a role in the accumulation of A-NK cells within cancer metastases.

Animals↗
PubMed1998

Sustained benefit of stenting chronic coronary occlusion: long-term clinical follow-up of the Stenting in Chronic Coronary Occlusion (SICCO) study.

OBJECTIVES: This study assessed the long-term clinical outcome of stenting chronic occlusions. BACKGROUND: In the Stenting in Chronic Coronary Occlusion (SICCO) study, patients were randomized to additional stent implantation (n = 58) or not (n = 59) after successful recanalization and dilation of a chronic coronary occlusion. Palmaz-Schatz stents were used with full anticoagulation. The previously published 6-month angiographic follow-up results showed reduction of the restenosis rate from 74% to 32%. METHODS: The primary end point was the occurrence of major adverse cardiac events (cardiac death, lesion-related acute myocardial infarction, repeat lesion-related revascularization or angiographic documentation of reocclusion). RESULTS: Late clinical follow-up was obtained in all patients at 33 +/- 6 months. Major adverse cardiac events occurred in 14 patients (24.1%) in the stent group compared with 35 patients (59.3%) in the percutaneous transluminal coronary angioplasty (PTCA) group (odds ratio 0.22, 95% confidence interval 0.10 to 0.49, p = 0.0002). Target vessel revascularization (including failed PTCA attempts) was performed in 24% of the stent group and in 53% of the PTCA group (p = 0.002). There were no events in the stent group after 8 months, whereas events continued to occur in the PTCA group. By multivariate analysis, allocation to the PTCA group, left anterior descending coronary artery lesion and lesion length were significantly related to the development of major adverse cardiac events. CONCLUSIONS: These data demonstrate the long-term safety and clinical benefit of stenting recanalized chronic occlusions. There is a continued risk of late clinical events related to nonstented lesions. Implantation of an intracoronary stent should therefore be considered after successful opening of a chronic coronary occlusion.

Angioplasty, Balloon, Coronary↗