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Biomedical subjects

P M Jansen

Publications and source records attributed to P M Jansen.

At least 19 recordsLinked to original sources
PubMed2005

Primary cutaneous marginal zone B-cell lymphoma: clinical and therapeutic features in 50 cases.

BACKGROUND: Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is a low-grade B-cell lymphoma that originates in the skin, with no evidence of extracutaneous disease. Studies focusing on the optimal treatment of PCMZL have not been published thus far. We describe 50 patients with PCMZL to further characterize clinical characteristics and outcome and, in particular, to evaluate our current therapeutic approach. OBSERVATIONS: The majority of the patients (36/50 [72%]) presented with multifocal skin lesions, and 14 patients (28%) presented with solitary or localized lesions. The initial treatment of patients with solitary lesions consisted of radiotherapy or excision, whereas patients with multifocal lesions received a variety of initial treatments, most commonly radiotherapy and chlorambucil therapy. Cutaneous relapses developed in 19 (48%) of 40 patients who had complete remission and were more common in patients with multifocal disease. After a median period of follow-up of 36 months, 2 patients developed extracutaneous disease, but none of the patients died of lymphoma. CONCLUSIONS: Patients with PCMZL who have solitary lesions can be treated effectively with radiotherapy or excision. For patients with PCMZL who have multifocal lesions, chlorambucil therapy and radiotherapy are suitable therapeutic options. In case of cutaneous relapses, the beneficial effects of treatment should carefully be weighed against the potential adverse effects.

Adult↗
PubMed2005

FISH analysis of MALT lymphoma-specific translocations and aneuploidy in primary cutaneous marginal zone lymphoma.

Primary cutaneous marginal zone lymphomas (PCMZL) share histological and clinical characteristics with mucosa-associated lymphoid tissue (MALT) lymphomas suggesting a common pathogenesis. A number of recurrent structural and numerical chromosomal aberrations have been described in MALT lymphoma, but their incidence in PCMZL is largely unknown, as is their relation with clinical and pathological data. In this study, the incidence of t(11;18)(q21;q21), t(1;14)(p22;q32), two different t(14;18)(q32;q21), involving either IGH/MALT1 or IGH/BCL2, and numerical aberrations of chromosomes 3, 7, 12 and 18 were analysed in 12 patients with PCMZL, with follow-up of up to 10 years. Nuclei were isolated from paraffin wax sections for dual-colour interphase fluorescence in situ hybridization (FISH) using various probe sets either flanking or spanning the involved genes. T(14;18)(q32;q21), with breakpoints in IGH and MALT1, was found in three cases. All three had partly monocytoid histological appearances and lacked blastic transformation. An additional trisomy of chromosome 3 was detected in one of these cases. Trisomy 18 was present in two lymphomas without monocytoid morphology. No definite correlation was seen with any clinical feature, including Borrelia serology. Neither t(11;18)(q21;q21), nor t(1;14)(p22;q32) or any other translocation involving IGH, BCL10, MALT1, BCL2 and API2, amplification or deletion of chromosomal region 11q21, 18q21, 1p22, and 14q32 was detected. These results indicate that a subgroup of PCMZL with partly monocytoid morphology is genetically related to MZL at other extranodal sites.

Adult↗
PubMed2004

[Three children with general malaise, fever, weight loss and cervical lymphadenopathy].

Combinations of symptoms such as general malaise, fever, weight loss and cervical lymphadenopathy have extensive differential diagnoses. In three children, girls aged 11, 13 and 17 years who presented with these symptoms, three different diagnoses were obtained. The first had Hodgkin's disease, the second mixed connective tissue disease (MCTD), and the third Hodgkin's disease in combination with systemic lupus erythematosus (SLE). A systematic approach is necessary for the diagnosis of such conditions. Careful history taking can provide valuable information while a physical examination provides essential clues for the final diagnosis. In particular, nail-fold lesions, tendon nodules and signs of myopathy should be looked for in patients suspected of MCTD and/or SLE. In Hodgkin's disease, generalized or localised lymphadenopathy combined with a short history of extreme fatigue are the most important. Additional investigations should be individualized in order to minimise the diagnostic delay and make possible early treatment.

Adolescent↗
PubMed2004

CD56+ hematological neoplasms presenting in the skin: a retrospective analysis of 23 new cases and 130 cases from the literature.

BACKGROUND: The aim of this study was to define prognostic parameters and guidelines for diagnosis and treatment for CD56+ hematological neoplasms with first presentation in the skin. PATIENTS AND METHODS: The study group included 153 cases (23 new and 130 from the literature). According to the World Health Organization classification, the group included 15 nasal and 38 nasal-type natural killer (NK)/T-cell lymphomas, 63 blastic NK-cell lymphomas, 14 cutaneous CD30+ lymphoproliferations, 10 cases of myeloid leukemia, six cases of subcutaneous panniculitis-like T-cell lymphoma (SCPLTCL) and seven peripheral T-cell lymphomas, unspecified. RESULTS: In general, these CD56+ hematological neoplasms had a poor prognosis, with only 27% of patients alive after a median follow-up of 12 months. The median survival was 13 months. Nasal and nasal-type NK/T-cell lymphomas and CD56+ SCPLTCL had the worst prognosis, with a median survival of 5, 6 and 5 months, respectively. Only nasal-type NK/T-cell lymphomas presenting with only skin lesions had a somewhat better prognosis (median survival 27 months). In blastic NK-cell lymphomas (median survival 14 months), age </=40 years, aggressive treatment with acute leukemia protocols and high TdT expression were associated with a more favorable prognosis. Striking similarities in histology, immunophenotype, clinical presentation and clinical behavior were found between blastic NK-cell lymphomas and CD56+ myeloid leukemias. CONCLUSIONS: CD56+ hematological neoplasms presenting in the skin have a poor prognosis, except for primary cutaneous CD30+ lymphoproliferations. The striking similarities between blastic NK-cell lymphomas and CD56+ myeloid leukemias presenting in the skin provide a rationale to treat these patients with more aggressive regimens, rather than with CHOP(-like) regimens and radiotherapy, which have proven to be inadequate therapies for this neoplasm.

Adolescent↗
PubMed2003

Bcl-2, Bcl-6 and CD10 expression in cutaneous B-cell lymphoma: further support for a follicle centre cell origin and differential diagnostic significance.

BACKGROUND: Primary cutaneous follicle centre cell lymphomas (PCFCCLs) are the most common type of cutaneous B-cell lymphoma. There is ongoing discussion on the origin of the neoplastic B cells in these PCFCCLs, and consequently on their relation to the groups of primary cutaneous marginal zone B-cell lymphomas (PCMZLs) and nodal follicular lymphomas. OBJECTIVES: To define better the neoplastic B cells in PCFCCLs, and to find out if differences in the expression of the antiapoptopic protein Bcl-2, and Bcl-6 and CD10, molecules which are normally expressed by the neoplastic B cells in nodal follicular lymphomas, might have diagnostic or prognostic significance in cutaneous B-cell lymphoproliferative disorders. METHODS: Pretreatment biopsies of well-defined groups of PCFCCL (n = 24), PCMZL (n = 14), primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg; n = 19), secondary cutaneous follicular lymphoma (n = 3) and cutaneous pseudo-B-cell lymphoma (n = 6) were investigated by immunohistochemistry for expression of Bcl-2, Bcl-6 and CD10. RESULTS: The PCFCCLs consistently expressed Bcl-6, whereas CD10 and Bcl-2 were expressed in only one and two of 24 cases, respectively. In contrast, PCMZLs were always negative for Bcl-6 and CD10, but were Bcl-2 positive, whereas skin and lymph node localizations of secondary cutaneous follicular lymphomas consistently expressed all of Bcl-2, Bcl-6 and CD10. Reactive follicle centre cells in pseudo-B-cell lymphomas expressed Bcl-6 (six of six cases) and CD10 (five of six cases), but not Bcl-2. PCLBCL-leg was Bcl-6 positive and CD10 negative in all cases, irrespective of clinical outcome, and strongly expressed Bcl-2 protein in all but two cases. CONCLUSIONS: The results of the present study provide further support for the follicle centre cell origin of both PCFCCL and PCLBCL-leg, and indicate that staining for Bcl-2, Bcl-6 and CD10 can serve as an important adjunct in the differential diagnosis of cutaneous B-cell lymphoproliferative disorders.

DNA-Binding Proteins↗
PubMed2001

The effect of a change in ambient temperature on blood pressure in normotensives.

The aim of this study was to investigate the influence of ambient temperature on blood pressure (BP). BP measurements were taken in 20 normotensive volunteers who stayed in Greenland for a 6-week period. Measurements of systolic (SBP), diastolic (DBP) and heart rate (HR) were taken before (3 sessions), during (7-8 sessions) and after the journey (3 sessions). Each session consisted of five BP measurements in the supine position after at least 5 min rest. All five readings were averaged. Temperature data (mean +/- s.d.), collected from meteorological services, before, during and after Greenland were 15.7 +/- 0.6, 0.5 +/- 1.5 and 8.2 +/- 0.8 degrees C. SBP values were 116 +/- 7.0, 122 +/- 7.6 and 116 +/- 7.4 and DBP 63 +/- 5.2, 66 +/- 5.8 and 65 +/- 6.5 mm Hg, respectively. HR amounted to 58 +/- 7.4, 61 +/- 6.7 and 60 +/- 7.4 bpm. Significant differences existed between, before and during for SBP and DBP and between, during and after for SBP. Readings were grouped in four categories based on the temperature at the time of reading. For SBP as well as DBP a clear dose-response relationship was demonstrated between low temperature and high BP, although for DBP only a few correlations were statistically significant. Mean correlation coefficients for SBP and DBP against temperature were -0.44 (P < 0.001) and -0.27 (P < 0.005), respectively. our results are in favour of a moderate, but both significant and relevant increase in sbp and dbp when moving from higher to lower ambient temperature.

Adult↗
PubMed2001

Lymphomatoid papulosis with a natural killer-cell phenotype.

Lymphomatoid papulosis (LyP) is defined as a recurrent self-healing papulonodular eruption with the histological features of a (CD30+) cutaneous T-cell lymphoma. The atypical cells usually have a CD3+/-, CD4+/-, CD8-, CD30+, CD56- T-cell phenotype. We report an unusual case of LyP, in which the atypical cells expressed a CD3-, CD4-, CD8-, CD30+, CD56+ phenotype. Detailed phenotypic and genotypic analysis confirmed that these cells had a natural killer (NK)-cell phenotype. Lymphomas with an NK-cell phenotype usually have a poor prognosis. However, the waxing and waning of papular lesions for more than 20 years and the excellent response to low-dose oral methotrexate in this patient suggest similar clinical behaviour to LyP cases with a T-cell phenotype.

CD56 Antigen↗
PubMed2000

Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli.

Plasma-derived antithrombin III (ATIII) prevents the lethal effects of Escherichia coli infusion in baboons, but the mechanisms behind this effect are not clear. In the present study, we evaluated the effects of recombinant human ATIII (rhATIII) on the clinical course and the inflammatory cytokine and coagulation responses in baboons challenged with lethal dose of E coli. Animals in the treatment group (n = 5) received high doses of rhATIII starting 1 hour before an E coli challenge. Those in the control group were administered saline. Survival was significantly improved in the treatment group (P =.002). Both groups had similar hemodynamic responses to E coli challenge but different coagulation and inflammatory responses. The rhATIII group had an accelerated increase of thrombin-ATIII complexes and significantly less fibrinogen consumption compared to controls. In addition, the rhATIII group had much less severe thrombotic pathology on autopsy and virtually no fibrinolytic response to E coli challenge. Furthermore, the rhATIII group had a significantly attenuated inflammatory response as evidenced by marked reduction of the release of various cytokines. We conclude that the early administration of high doses of rhATIII improves the outcome in baboons lethally challenged with E coli, probably due to the combined anticoagulation and anti-inflammatory effects of this therapy. (Blood. 2000;95:1117-1123)

Animals↗
PubMed1999

Staging of the baboon response to group A streptococci administered intramuscularly: a descriptive study of the clinical symptoms and clinical chemical response patterns.

Group A streptococcal infections, ranging from necrotizing fasciitis and myositis to toxic shock syndrome, have increased over the last 10 years. We developed the first primate model of necrotizing fasciitis and myositis. Thirteen baboons were inoculated intramuscularly with group A streptococci (GAS). Eleven animals survived for > or = 11 days before sacrifice, and two animals died within 2 days. The site of inoculation of the survivors exhibited an intense neutrophilic influx (stage I), followed by a lymphoplasmacytic influx (stages II and III). This was accompanied by the appearance of markers of an acute and then a chronic systemic inflammatory response. In contrast, the site of inoculation of the two nonsurvivors exhibited intravascular aggregates of neutrophils at its margin with no influx of neutrophils and with extensive bacterial colonization. We conclude that GAS inoculation induces a local and systemic acute neutrophilia followed by a chronic lymphoplasmacytic response; failure, initially, of neutrophilic influx into the site of inoculation predisposes to systemic GAS sepsis and death; and this three-stage primate model approximates the human disease.

Animals↗
PubMed1998

Effect of C1 inhibitor on inflammatory and physiologic response patterns in primates suffering from lethal septic shock.

We evaluated the effect of C1 inhibitor (C1-inh), an inhibitor of the classical pathway of complement and the contact system, on the physiologic and inflammatory response in baboons suffering from lethal Escherichia coli sepsis. Five animals pretreated with 500 U/kg C1-inh (treatment group; n = 5), followed by a 9-h continuous infusion of 200 U/kg C1-inh subsequent to bacterial challenge, were compared with five controls receiving E. coli alone. Of the treatment group, one animal survived and another lived beyond 48 h, whereas all control animals died within 27 h. In four of five treated animals, less severe pathology was observed in various target organs. C1-inh administration did not prevent the hemodynamic or hematologic changes observed upon E. coli infusion. The activation of fibrinolysis and the development of disseminated intravascular coagulation were essentially unaffected by C1-inh. However, C1-inh supplementation significantly reduced decreases in plasma levels of factor XII and prekallikrein and abrogated the systemic appearance of C4b/c, indicating substantial inhibition of activation of the contact system and the classical complement pathway, respectively. Furthermore, treated animals displayed a reduced elaboration of various cytokines including TNF, IL-10, IL-6, and IL-8. Thus, the administration of C1-inh may have a beneficial but modest effect on the clinical course and outcome of severe sepsis in nonhuman primates. We suggest that activated complement and/or contact system proteases may, at least in part, contribute to the attendant manifestations of septic shock through an augmentation of the cytokine response.

Animals↗
PubMed1998

Force generation and shift of mass between myosin and actin in skinned striated muscle fibres at low calcium concentrations.

Skinned muscle fibres from the gracilis muscle of the rabbit were used to record small angle X-ray diffraction spectra under various contractile conditions. The intracellular calcium concentration, expressed as pCa, was varied between 8.0 and 5.74. Equatorial diffraction spectra were fitted by a function consisting of five Gaussian curves and a hyperbola to separate the (1.0), (1.1), (2.0), (2.1) and Z-line diffraction peaks. The hyperbola was used to correct for residual scattering in the preparation. The ratio between the intensities of the (1.1) and (1.0) peaks was defined as the relative transfer of mass between myosin and actin, due to crossbridge formation after activation by calcium. The relation between the ratio and the relative force of the fibre (normalized to the force at pCa 5.74 and sarcomere length 2.0 microns) was linear. At high pCa (from pCa 6.34 to 8.0) no active force was observed, while the ratio still decreased. Sarcomere length was recorded by laser diffraction. The laser diffraction patterns did not show changes in sarcomere length due to activation in the high pCa range (between 8.0 and 6.34). From these results the conclusion is drawn that crossbridge movement occurs even at subthreshold calcium concentrations in the cell, when no active force is exerted. Since no force is generated this movement may be related to crossbridges in the weakly bound state.

Actins↗
PubMed1997

Effect of a recombinant dimeric tumor necrosis factor receptor on inflammatory responses to intravenous endotoxin in normal humans.

To determine the role of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-induced inflammation, 12 healthy subjects received an intravenous injection with LPS (2 ng/kg) preceded by infusion of either a recombinant human dimeric TNF receptor type II-IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) or vehicle (n = 6) from -30 minutes to directly before LPS injection. LPS elicited a transient increase in plasma TNF activity, peaking after 1.5 hours (219 +/- 42 pg/mL; P < .05). Infusion of TNFR:Fc completely neutralized endogenous TNF activity. LPS administration was associated with an early activation of fibrinolysis (plasma concentrations of tissue-type plasminogen activator, plasminogen activator activity, and plasmin-alpha2-antiplasmin complexes), followed by inhibition (plasma plasminogen activator inhibitor type I), changes that were completely prevented by TNFR:Fc. By contrast, TNFR:Fc did not influence LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1 + 2 and thrombin-antithrombin III complexes). TNFR:Fc strongly inhibited endothelial cell activation (plasma levels of soluble E-selectin), modestly reduced neutrophil responses (neutrophilia and plasma concentrations of elastase-alpha1-antitrypsin complexes and lactoferrin), but did not affect the release of secretory phospholipase A2 or lipopolysaccharide-binding protein (P > .05). Infusion of TNFR:Fc only (without LPS) in another 6 normal subjects did not induce any inflammatory response. These data indicate that TNF is involved in only some inflammatory responses to intravenous LPS in humans.

Adult↗
PubMed1997

Epinephrine exerts anticoagulant effects during human endotoxemia.

To determine the effect of a physiologically relevant elevation in the plasma concentrations of epinephrine on the activation of the hemostatic mechanism during endotoxemia, 17 healthy men were studied after intravenous injection of lipopolysaccharide (LPS, 2 ng/kg), while receiving a continuous infusion of epinephrine (30 ng/kg/min) started either 3 h (n = 5) or 24 h (n = 6) before LPS injection, or an infusion of normal saline (n = 6). Activation of the coagulation system (plasma concentrations of thrombin-antithrombin III complexes and prothrombin fragment F1+2) was significantly attenuated in the groups treated with epinephrine when compared with subjects injected with LPS only (P <0.05). Epinephrine enhanced LPS-induced activation of fibrinolysis (plasma levels of tissue-type plasminogen activator and plasmin-alpha2-antiplasmin complexes; P <0.05), but did not influence inhibition of fibrinolysis (plasminogen activator inhibitor type I). In subjects infused with epinephrine, the ratio of maximal activation of coagulation and maximal activation of fibrinolysis was reduced by >50%. Hence, epinephrine exerts antithrombotic effects during endotoxemia by concurrent inhibition of coagulation, and stimulation of fibrinolysis. Epinephrine, whether endogenously produced or administered as a component of treatment, may limit the development of disseminated intravascular coagulation during systemic infection.

Adult↗
PubMed1997

Effects of IL-10 on systemic inflammatory responses during sublethal primate endotoxemia.

IL-10 protects mice from LPS-induced lethality. To determine the effects of IL-10 on LPS-induced inflammatory responses, six Papio anubis baboons were i.v. injected with a sublethal dose of LPS (Salmonella typhimurium; 500 microg/kg) directly preceded by either human rIL-10 (n = 3, 500 microg/kg) or diluent (n = 3). IL-10 strongly inhibited LPS-induced release of TNF, IL-6, IL-8, and IL-12 (all p < 0.05). By contrast, IL-10 did neither influence the activation of the coagulation system (plasma levels of thrombin/antithrombin III complexes), nor the activation of the fibrinolytic system (plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor type I, and plasmin/alpha 2-antiplasmin complexes). IL-10 modestly attenuated neutrophilic leukocytosis and neutrophil degranulation (plasma concentrations of elastase/alpha1-antitrypsin complexes) (both p < 0.05). Changes in surface TNF receptor expression on circulating granulocytes were not affected by IL-10. These results suggest that during sublethal endotoxemia the predominant anti-inflammatory effect of IL-10 treatment is inhibition of proinflammatory cytokine release.

Animals↗
PubMed1997

Induction of gelatinase B and MCP-2 in baboons during sublethal and lethal bacteraemia.

Intravenous injection of sublethal or lethal doses of Escherichia coli in baboons resulted in increased serum levels of the matrix metalloprotease gelatinase B and the chemokine monocyte chemotactic protein 2 (MCP-2). In both animal models, gelatinase B appeared faster than MCP-2. After sublethal challenge, serum levels of gelatinase B and MCP-2 were found to be correlated, reaching peak levels between 2 and 4 h after bacterial challenge. After lethal challenge, however, MCP-2 tended to increase until 10 h. The kinetics of appearance suggest induction of release of gelatinase B and de novo synthesis and secretion of MCP-2, both by endotoxin.

Animals↗
PubMed1997

Pretreatment with a 55-kDa tumor necrosis factor receptor-immunoglobulin fusion protein attenuates activation of coagulation, but not of fibrinolysis, during lethal bacteremia in baboons.

Baboons (Papio anubis) receiving a lethal intravenous infusion with live Escherichia coli were pretreated with either a 55-kDa tumor necrosis factor (TNF) receptor-IgG fusion protein (TNFR55:IgG) (n = 4, 4.6 mg/kg) or placebo (n = 4). Neutralization of TNF activity in TNFR55:IgG-treated animals was associated with a complete prevention of mortality and a strong attenuation of coagulation activation as reflected by the plasma concentrations of thrombin-antithrombin III complexes (P < .05). Activation of fibrinolysis was not influenced by TNFR55:IgG (plasma tissue-type plasminogen activator and plasmin-alpha2-antiplasmin complexes), whereas TNFR55:IgG did inhibit the release of plasminogen activator inhibitor type I (P < .05). Furthermore, TNFR55:IgG inhibited neutrophil degranulation (plasma levels of elastase-alpha1-antitrypsin complexes, P < .05) and modestly reduced release of secretory phospholipase A2. These data suggest that endogenous TNF contributes to activation of coagulation, but not to stimulation of fibrinolysis, during severe bacteremia.

Animals↗
PubMed1997

Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons.

Patients with sepsis or after major surgery have decreased plasma levels of the anticoagulant protein antithrombin. In such patients elevated levels of interleukin-6 (IL-6) are present and this interleukin is known to induce positive and negative acute phase responses. To investigate the possibility that antithrombin acts as a negative acute phase response-protein we performed studies on the human hepatoma cell line HepG2 in vitro and baboons in vivo. HepG2 cells were treated with recombinant human IL-6, IL-1beta, or combinations of the latter two, and tested for production of antithrombin, fibrinogen and prealbumin (transthyretin). This treatment resulted in a dose dependent increase in fibrinogen concentration (with a maximum effect of 2.8-2.9-fold) and a dose dependent decrease in prealbumin (with a maximum effect of 0.6-0.7-fold) and antithrombin concentrations (with a maximum effect of 0.6-0.8-fold). Simultaneous treatment of the HepG2 cells with IL-6 (1,000 pg/ml or 2,500 pg/ml) and IL-1beta (25 pg/ml), provided more extensively decreased prealbumin (0.8 and 0.6-fold, respectively) and antithrombin concentration (0.7 and 0.6-fold, respectively) compared to the single interleukin treatment at these concentrations. Baboons treated with 2 microg IL-6 x kg body-weight(-1) x day(-1) showed increased plasma CRP levels (59-fold, p <0.05) and decreased prealbumin (0.9-fold, p <0.05) and antithrombin (0.8-fold, p <0.05) plasma levels, without evidence for coagulation activation. Our results indicate that antithrombin acts as a negative acute phase protein, which may contribute to the decreased antithrombin plasma levels observed after major surgery or in sepsis.

Acute-Phase Reaction↗