Biomedical subjects

M Ekman

Publications and source records attributed to M Ekman.

At least 37 records · Page 2Linked to original sources

PubMed1998

Blood dendritic cells from myeloma patients are not infected with Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8).

In recent studies, the sequence of Kaposi's sarcoma-associated herpes virus (KSHV) or human herpes virus-8 (HHV-8) was detected in dendritic cells (DC) of patients with multiple myeloma (MM). A concern was raised whether there is an causal association between the viral infection and development of these tumors. In the present study, we have examined DC generated from blood adherent cells from 8 Swedish MM patients at different clinical stages and 2 patients with monoclonal gammopathy of undetermined significance. In addition, 6 myeloma cell lines and bone marrow cells from 2 MM patients were also studied. By polymerase chain reaction (PCR), including nested PCR, no virus DNA was demonstrable in the patients' DC or in myeloma cell lines or fresh bone marrow cells. Moreover, no antibody against KSHV was found in the serum of these 10 patients. Thus, our results indicate that blood-derived DC of MM patients in Sweden usually are not infected with KSHV/HHV-8. This study also suggests that KSHV/HHV-8 is not regularly associated with MM and consequently does not play a primary role in the pathogenesis of these tumors.

Adult↗

PubMed1998

Cloning, expression pattern, and chromosomal assignment to 16q23 of the human gamma-adaptin gene (ADTG).

Adaptins are important components of clathrin-coated vesicles transporting ligand-receptor complexes from the plasma membrane or from the trans-Golgi network to lysosomes. Adaptins, together with medium and small subunits, form a heterotetrameric complex called an adaptor, whose role is to promote the formation of clathrin-coated pits and vesicles. We present the cloning and sequencing of the human gamma-adaptin cDNA (HGMW-approved symbol ADTG) consisting of 3723 bp with an open reading frame capable of encoding a protein of 825 amino acids, 98.9% identical to the mouse protein. Northern blot analysis of the mouse and human gamma-adaptin genes revealed a ubiquitous and abundant expression, except in human adult lung. Using a monochromosomal somatic cell hybrid panel and fluorescence in situ hybridization, we mapped this gene to human chromosome 16q23, which is syntenic with mouse chromosome 8, band D. In addition, we localized genes for two other components of the AP-1 adaptor, i.e., the medium (AP47) and small (AP19) subunits, to chromosomes 19 and 7, respectively. Expression analysis of these genes in human tissues revealed ubiquitously expressed transcripts of approximately 2.5 and 1.5 kb, respectively.

Adaptor Protein Complex gamma Subunits↗

PubMed1998

Immunoadsorption for removal of inhibitors: update on treatments in Malmö-Lund between 1980 and 1995.

Treatment of severe bleeding and the performance of surgery in haemophilia patients with inhibitors creates severe problems. It is generally agreed that treatment is most effective if circulating levels of factor VIII/IX can be achieved long enough for control of haemostasis. Immunoadsorption with protein A for the removal of inhibitor has improved treatment for patients with initial inhibitor titres too high to neutralize by infusion alone. This is a summary of our experience in Malmö regarding immunoadsorption and haemostasis. A total of 19 applications with immunoadsorption in 10 patients were performed. On all occasions it was possible to eliminate totally the inhibitor or reduce it to low levels that could easily be neutralized with factor concentrate. Haemostatic levels of coagulation factors could be maintained for 5-9 days in all but one patient. This period was sufficient to stop ongoing haemorrhage or prevent excessive bleeding at surgical interventions.

Factor IX↗

PubMed1997

Expression of HHV-8 latency-associated T0.7 RNA in spindle cells and endothelial cells of AIDS-associated, classical and African Kaposi's sarcoma.

Analysis by polymerase chain reaction (PCR) and serological studies have demonstrated a close association between the novel human herpes virus, Kaposi's sarcoma-associated herpes virus (KSHV) or human herpes virus-8 (HHV-8) and the development of Kaposi's sarcoma (KS). To clarify the role of HHV-8 in KS pathogenesis, we investigated at the cellular level by in situ hybridization the expression of a recently described 0.7-kb HHV-8-encoded mRNA (T0.7 mRNA) in KS tissues of different epidemiological origin (AIDS-KS, African endemic KS and classical KS). The T0.7 mRNA likely encodes a small membrane protein, supposedly expressed in latently HHV-8-infected cells. Indeed, we detected T0.7 mRNA in virtually all cells of the cell line BCBL-1 established from a body cavity-based lymphoma (BCBL) and latently infected with HHV-8. In all KS biopsies examined, independent of their epidemiological type, the late-stage (nodular) KS tissues showed a high level of T0.7 mRNA expression in typical KS spindle cells but also in endothelial cells lining blood vessels, indicating latent HHV-8 infection of these cells. The presence of T0.7-expressing cells was restricted to KS tumor tissue and therefore appears to indicate an important role of latent HHV-8 infection in KS pathogenesis.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Differentiation of human dendritic cells from monocytes in vitro.

Since either macrophages (Mphi) or dendritic cells (DC) differentiate from monocytes (MO) depending on culture conditions, we investigated the relationship of the DC and Mphi differentiation pathways. Culturing MO-enriched blood mononuclear cells with Mphi colony-stimulating factor (M-CSF) or with granulocyte/Mphi (GM)-CSF induced Mphi with a different morphology and CD14/CD1a expression. In contrast, in cultures with GM-CSF and interleukin (IL)-4, cells rapidly became nonadherent and acquired DC morphology, ultrastructure, CD1a expression, and most DC markers; they lost membrane CD14 and CD64 and capacity of phagocytosis, displayed less CD68 than Mphi, but retained nonspecific esterase activity. These DC directly developed from MO without proliferation inasmuch as only day 0 FACS-sorted MO, but not small CD14- cells, differentiated into DC when cultured with GM-CSF and IL-4, or to Mphi with M-CSF While overall cell numbers declined, DC numbers plateaued from culture day 2 onwards, indicating that most had differentiasted by then. This differentiation was radioresistant and occurred without [3H]thymidine incorporation. Commitment to differentiate into DC with GM-CSF and IL-4 was irreversible by day 2, since discontinuing IL-4 at this point did not revert cells to Mphi. Alternatively, cells rapidly converted to DC when IL-4 was added from day 2 to cultures initiated with GM-CSF only. If cultures were initiated with M-CSF and switched to GM-CSF and IL-4 after 2 or 5 days, about half of the cells still converted to DC. Thus, the capacity of MO and even of Mphi to differentiate into DC was conserved for at least this period. The increased capacity to stimulate the mixed leukocyte reaction correlated with the relative number of CD1a+ cells at any time and under each condition tested, a confirmation that these cells functionally qualify as DC. Thus, MO and even Mphi can be directed to differentiate into DC depending on the cytokine microenvironment.

Antigens, CD1↗

PubMed1997

No effect of a new second-generation B-domain-deleted recombinant product on lymphocyte transformation in vitro: a study of plasma-derived and recombinant products.

Immunomodulatory effects of various factor VIII and factor IX clotting factor concentrates (CFCs) and of albumin were evaluated by a sensitive assay measuring the incorporation of 3H-thymidine in phytohaemagglutinin-stimulated lymphocytes in the presence of monodansylthiacadaverine. In contrast to previous findings by others, we found lymphocyte transformation to be inhibited by all plasma-derived factor VIII concentrates at concentrations of 0.02, 0.2 and 2.0 IU/ml, including those purified by monoclonal antibodies (P < 0.05). Kryobulin TIM3 had the most pronounced effect. In addition, three plasma-derived human albumin preparations exerted a similar inhibitory effect as the factor VIII concentrates, whereas the corresponding plasma-derived factor IX concentrates only manifested minor immunomodulatory effects. Of the recombinant preparations, only Recombinate exerted an inhibitory effect at 0.02 and 0.2 IU/ml, whereas both Kogenate and Recombinate decreased 3H-thymidine incorporation at 2.0 IU/ml (P = 0.01). No immunomodulatory effect at all was observed with r-VIII SQ, a new B-domain-deleted recombinant factor VIII preparation free from added albumin. The significance of this finding regarding immunological side-effects including inhibitor development remains to be evaluated, but this second-generation recombinant product opens up new and interesting perspectives yet to be explored.

Cadaverine↗

PubMed1996

SIV infection of monkey spleen cells including follicular dendritic cells in different stages of disease.

Immunoaffinity enriched spleen follicular dendritic cells (FDCs), lymphocytes, and macrophages from SIVsm-inoculated cynomolgus monkeys (Macaca fascicularis) at different stages of disease were compared for latent and productive SIV infection. Analysis of FDCs by in situ hybridization, electron microscopy, and coculture assays indicated that comparatively high levels of virus were associated with the FDC fraction. Polymerase chain reaction (PCR) and RT-PCR results revealed that the levels for SIVpol DNA did not correlate with the level of env mRNA in the various cell subsets, suggesting differences in latency. Limiting dilution assays for spliced env mRNA showed a 10-100-fold higher amount of env mRNA in FDCs than in other spleen cell subsets early during SIV infection. At late stages of disease, the number of productively infected FDCs significantly decreased in parallel with a marked reduction of the FDC network and follicular involution. Our findings indicate that destruction of FDCs probably reflects a cytopathic effect of SIV and/or the activity of specific antiviral cytotoxic T lymphocytes.

Animals↗

PubMed1996

Liver uptake function measured by IODIDA clearance rate in liver transplant patients and healthy volunteers.

Hepatobiliary scintigraphy with 99Tc(m)-diethyl-iodo-HIDA (IODIDA), an iminodiacetic acid derivative, is used to assess hepatocyte function and to visualize the hepatobiliary system. The aim of this study was to evaluate whether it is possible to describe liver function by calculating the clearance rate of IODIDA from the blood. Clearance rate was evaluated in 18 liver transplant patients (28 studies) and 11 healthy volunteers (11 studies). Two different clearance rates were calculated: the clearance of IODIDA from the blood due to liver uptake and the total clearance of IODIDA from the blood due to all possible routes of elimination. Both for the healthy controls and the liver transplant patients, there was an excellent correlation between these two methods (r = 0.92 and r = 0.93, respectively), indicating that the liver is the only essential pathway for elimination of IODIDA from the blood. The difference in clearance rate between healthy controls and liver transplant patients was highly significant (P < 0.01), corresponding to the clinical condition of the two groups. We conclude that the clearance rate of IODIDA, based on a simple measurement from the time-activity curve derived from a blood pool region of interest, is a reliable test of liver function.

Adolescent↗

PubMed1996

Polyomavirus-infected oligodendrocytes and macrophages within astrocytes in progressive multifocal leukoencephalopathy (PML).

Polyomavirus-infected oligodendrocytes and in some instances virus-carrying macrophages were demonstrated within the cytoplasm of astrocytes by double immunostaining of brain lesions in a case of PML following bone marrow transplantation. The infected oligodendrocytes and CD68+ cells were usually partially or completely invested by the cytoplasm of reactive and infected or noninfected giant pleomorphic astrocytes. By electron microscopy (EM), internalized infected oligodendrocytes were shown to release polyomavirus particles possibly infectious to the astrocytes. These observations seem to indicate that astrocytes in PML can become infected by direct contact with internalized infected oligodendrocytes and possibly also by virus-loaded macrophages. Correspondingly, astrocyte/oligodendrocyte/macrophage cell-to-cell interactions appear to play an important role in the pathogenesis of PML lesions.

Astrocytes↗

PubMed1996

Ethanol decreases nocturnal plasma levels of thyrotropin and growth hormone but not those of thyroid hormones or prolactin in man.

Previous studies on the effects of ethanol on circulating pituitary hormones have been carried out mostly during daytime when the secretion of these hormones is generally at a nadir. Therefore, we studied the effects of ethanol on the nocturnal secretion of GH, PRL, TSH, and thyroid hormones (protocol I, nine healthy subjects, five women) and on the TSH and PRL responses to synthetic TRH (protocol II, healthy subjects, four women). Ethanol was given in doses of 0, 0.5 or 1.0 g/kg of BW(protocol I) and 0 or 1.0 g/kg (protocol II) and ingested po at 1900-1945 h. In protocol I, plasma GH rose from 0.6 +/- 0.2 microgram/L (mean +/- SE) at 2200 h to 25.0 +/- 4.3 micrograms/L at 0100 h in control subjects and was almost completely inhibited at 4.5 +/- 1.7 micrograms/L at 0100 h in subjects receiving 1.0 g/kg ethanol (P < 0.01). In subjects receiving 0.5 g/kg ethanol, the inhibition was also significant (P < 0.01), plasma GH being 8.2 +/- 2.5 micrograms/L at 0100 h. Plasma GHRH was measured after solid phase separation in RIA, but it did not show any ethanol-related changes. Plasma PRL exhibited a clear diurnal rhythm in control subjects and rose from 77 +/- 16 at 1800 h to 248 +/- 62 micrograms/L at 0700 h (P < 0.01). The plasma PRL profile was not affected by ethanol. Plasma TSH was 1.4 +/- 0.2 mU/L at 1800-2200 h and rose to 2.3-2.4 mU/L for 0100-0700 h (P < 0.001) in the control subjects. Ethanol 1.0 g/kg suppressed plasma TSH to 1.4 +/- 0.2 mU/L (P < 0.05 at 0100 h and P < 0.01 at 0200 h). According to the area under the curve analyses, the suppression in the nocturnal TSH was 32% in the 0.5 g/kg group and 45% in the 1.0 g/kg group (P < 0.05 for both cases). Circulating free or total T3 and T4 did not show any statistically significant changes that could explain the ethanol-induced inhibition in the nocturnal TSH peak. In protocol II, synthetic TRH (1 microgram/kg BW) was given intravenously, and blood samples were collected before, at 20 and 60 min. TRH significantly stimulated plasma TSH and PRL, but ethanol (1.0 g/kg BW) had no effect on these responses. In conclusion, small amounts of ethanol have unexpectedly great effects on nocturnal surges of TSH, and especially on those of GH, that are apparently mediated by suprapituitary mechanisms. On the other hand, ethanol did not affect the nocturnal PRL surge. These inhibitory effects of ethanol may have unfavorable effects on growth and metabolism in adolescent drinkers.

Adult↗

PubMed1995

Parallel existence of Epstein-Barr virus (EBV) positive and negative cells in a sporadic case of Burkitt lymphoma.

In the Burkitt lymphoma line Oma-BL1, EBV positive and negative cells coexist. We demonstrate that EBV positive and negative subclones are identical with respect to chromosome markers and HLA type and that the same c-myc rearrangement occurs in all the subclones. This shows that the tumor cells are derived from the same patient and are of monoclonal origin. In the positive subclones, the EBV genome was stably maintained in the episomal form. The EBV negative subclones could be derived from previously uncloned tumor cells in early passage, but not from the EBV positive subclones.

Adolescent↗

PubMed1995

B-cell lymphomagenesis in SIV-immunosuppressed cynomolgus monkeys.

B-cell lymphomas developed frequently (approx. 40%) in SIVsm (SMM3) immunosuppressed monkeys and were mostly extranodal, aggressive and all associated with an EBV-related simian herpes virus operationally designated herpes virus Macaca fascicularis (HVMF-I). Lymphoma tissues from 21 monkeys were studied by PCR and DNA PAGE for mono/oligoclonality of the VDJ-rearranged IgH genes. Most lymphomas (n = 15) showed a monoclonal and approximately 1/3 (n = 6) an oligoclonal VDJ rearrangement pattern. The time after infection to tumor presentation was significantly shorter for oligoclonal than for monoclonal lymphomas, suggesting that oligoclonal selection frequently precedes the outgrowth of a single malignant clone. Comparison of the VDJ rearrangements in an established lymphoma cell line and the original, oligoclonal lymphoma tissue indicated in vitro selection of one HVMF-infected clone. Longitudinal studies of sequential lymph-node biopsies showed that the malignant lymphoma clone in 3 out of 8 lymphomas could be identified as a predominant clone in lymph nodes 2-12 months after SIV infection and 6-10 months before clinical presentation of the lymphomas. VDJ-rearranged DNA corresponding to that of the lymphomas was also detected in most sera at the time of lymphoma manifestation but not in corresponding PBL preparations. Clearly, the SIVsm AIDS model in cynomolgus monkeys represents a powerful tool for biological and clinical studies of herpes-virus-associated lymphomagenesis in immunosuppressed states.

Animals↗

PubMed1995

Thymic immunopathology and progression of SIVsm infection in cynomolgus monkeys.

Thymuses from 22 cynomolgus monkeys infected with simian immunodeficiency virus (SIVsm) developed characteristic cortical and medullary changes including formation of B-cell follicles (8/21) and accumulation of virus immune complexes. Advanced thymic histopathology was correlated with more pronounced immunodeficiency. SIVsm provirus was detected by polymerase chain reaction (PCR) in most (16/18) thymuses and spliced viral env mRNA in 3 (3/7) thymuses with advanced histopathologic changes indicative of thymic SIVsm replication. By combined in situ hybridization (ISH) and immunohistochemistry, viral RNA was localized mainly to the follicular dendritic network, macrophages, multinucleated giant cells, and lymphocytes of the medullary regions. Latent infection by an Epstein-Barr-related herpesvirus (HVMF1) was also found by PCR and by ISH in medullary regions of three (3 of 8) thymuses with B-cell follicles, suggestive of an inductive role for B-cell proliferation in these thymuses. In a control group of HIV-2-infected nonimmunosuppressed monkeys, no comparable thymic changes were observed. Our results indicate that SIV, and probably by analogy HIV, can have direct and diverse pathogenic effects on the thymus that are important in the development of simian (human) AIDS.

Animals↗

PubMed1995

Ethanol induces a paradoxical simultaneous increase in circulating concentrations of insulin-like growth factor binding protein-1 and insulin.

The aim of this study was to examine the effect of acute alcohol intake on circulating concentrations of insulin, C-peptide, insulin-like growth factor (IGF) binding protein-1 (IGFBP-1), and plasma glucose levels. We measured these parameters for 12 hours after administration of 0, 0.5, or 1.0 g ethanol/kg body weight to nine healthy volunteers between 7:00 and 7:45 PM according to a randomized, double-blind, crossover design. Following a snack at 9:00 PM, plasma insulin (P < .05) and C-peptide (P < .01) concentrations were significantly increased at 10:00 PM in the 1.0-g group as compared with the control group. C-peptide to insulin molar ratios were significantly higher (P < .05) in both ethanol groups at 10:00 PM and 2:00 AM than in the control group. No differences were observed in plasma glucose levels between the three groups. Plasma IGFBP-1 levels showed a dose-dependent increase in the ethanol groups, and remained increased from 10:00 PM for 3 hours (P < .05 or less) at the lower dose and for 6 hours (P < .05 or less) at the higher dose. These observations indicate that ethanol-induced postprandial hyperinsulinemia is due to increased insulin secretion and that alcohol may increase hepatic insulin extraction. The lack of any effect on plasma glucose levels suggests that alcohol intake must be associated with decreased insulin sensitivity. Alcohol intake results in a paradoxical increase in peripheral concentrations of IGFBP-1 despite simultaneous hyperinsulinemia. This implies that ethanol has a direct stimulatory effect on hepatic IGFBP-1 synthesis.

Adult↗

PubMed1995

A role for a new herpes virus (KSHV) in different forms of Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a previously rare, tumour-like lesion of controversial biological nature. KS has since the early 1980s become frequent in patients with AIDS, particularly in homosexuals. KS is also endemic in Central Africa predominantly in otherwise healthy men but also in women and children. Recently, evidence for the presence of novel, herpes virus DNA sequences in more than 90% of AIDS Kaposi lesions (AKS) was presented. This DNA was identified using representational difference analysis (RDA) generating short, unique sequences with variable homology to several herpes virus, but no intact virus was recovered. If these DNA-sequences are also present in other, non-HIV-associated forms of Kaposi's sarcoma this would strongly suggest a specific, aetiopathological involvement of this putative new herpes virus in the pathogenesis of Kaposi's sarcoma, rather than a contamination of yet another opportunistic virus in immunosuppressed AIDS patients.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Do highly physically active females have a lowered basal metabolic rate?

In several studies estimated energy intake has been found to be low compared with estimated energy expenditure in female athletes. It has therefore been suggested that female athletes may have a depressed basal energy expenditure (BMR). The main purpose of the present study was to explore this possibility by measuring BMR in physically extremely active females. Eight female dancers and 7 controls with low physical activity, all musicians, were studied; the variables measured included body weight, height, skinfold thickness and total body potassium. BMR was measured by indirect calorimetry. In conclusion, the present study lends no support to the idea of a lowered basal metabolic rate in female athletes as an explanation of the general finding of a lower estimated energy intake than energy expenditure in this type of subjects.

Adult↗

PubMed1995

Closed-line integral optimization edge detection algorithm and its application in equilibrium radionuclide angiocardiography.

UNLABELLED: Automatic evaluation of left ventricular (LV) function using equilibrium radionuclide angiocardiography requires an edge detection algorithm to correct and reproducibly delineate the left ventricle. Available algorithms, usually based on differentiation of a radial profile, generally suffer from low precision due to low signal-to-noise ratios and overlapping structures, for example, the left atrium. METHODS: An edge detection algorithm was developed based on the assumption that the LV border can be defined as the maximum, normalized, closed-line integral of a closed curve in a vector field derived by image differentiation. It is further assumed that the closed curve can be described by a Fourier expansion with a limited number of harmonics. Regions of interest (ROIs) generated by this algorithm were compared with ROIs generated by an algorithm based on a combination of thresholding and second-order derivatives. RESULTS: This algorithm delineates the left ventricle and gives results more closely related to ROIs generated manually than the algorithm combining thresholding and the second-order derivative. Our algorithm can also handle the problem of overlapping structures, as demonstrated in phantom simulations. CONCLUSION: The concept of a maximum, normalized closed-line integral will improve the delineation of the LV in an equilibrium radionuclide angiocardiography study. The problem of overlapping structures is overcome by this algorithm because it takes into consideration global edge information.

Algorithms↗

PubMed1994

Oral hairy leukoplakia: pathogenetic aspects and significance of the lesion.

Oral hairy leukoplakia in HIV-seropositive persons is considered as a highly serious sign and places the patient in the AIDS-related complex group according to the classification recommended by the Centers for Disease Control. Epstein-Barr virus (EBV) is thought to be the cause. Based on the investigation of 14 of our own cases and a review of the literature, we conclude that so called hairy leukoplakia does not have a specific histopathologic pattern. Identical lesions can be caused by fungus infection, or biting and other kinds of mechanical irritation. Both fungal infection and EBV infection have been proven in a high percentage of the lesions. However, EBV has been found also in apparently normal oral mucosa. This questions the assumption that the virus is the cause of the lesions. In our investigation the presence of "hairy leukoplakia" did not reflect the clinical status of the patient. The best indicator of the clinical status was the T-lymphocyte subset CD4+ number in the peripheral blood. It appears that low CD4+ counts, candidiasis and the presence of replicating EBV in the epithelial cells are parallel markers of increasing immunodeficiency.

Adult↗