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Biomedical subjects

J Jansen

Publications and source records attributed to J Jansen.

At least 73 records · Page 4Linked to original sources

Trigeminal neuralgia. Clinical manifestations of first division involvement.

A series of 19 patients with what originally had been diagnosed as a first division (V1) trigeminal neuralgia was collected. The inclusion criteria were severe, rather short-lasting pain attacks within the V1 area, combined with trigger mechanisms. There were 10 women and 9 men, and the mean age of onset was 57.8 years. Fifteen of 16 with adequate information on attack duration had paroxysms of a "few seconds" duration or less, whereas 10 patients had paroxysms lasting < or = 2 seconds. In an exceptional case, only "more long-lasting" attacks (greater than 30 seconds' duration) were experienced. In regard to autonomic phenomena, lacrimation was most frequently present (in a total of 8 patients; 3 rather regularly, 5 more irregularly). The combination of lacrimation, conjunctival injection, and rhinorrhea was present in only 2 (of 19), and in neither of them in a major way. Typically, autonomic phenomena occurred during the later stages of disease and during particularly severe and long-lasting attacks. Seven of 14 with adequate information also had nocturnal attacks. Initially, a more or less complete carbamazepine effect was reported by 10 of 13 patients. Precipitation mechanisms were the same as with second and third division tic, but were mainly located within the V1 area, particularly initially. A comparison with SUNCT syndrome has been made. SUNCT is a predominantly male disorder, with only exceptional attacks of < or = 10 seconds' duration, and generally with attacks of 15 seconds or longer. Autonomic symptoms and signs are more pronounced than in V1 tic. Carbamazepine generally provides minor, if any, benefit in SUNCT. The present work strongly indicates that the two disorders are essentially different.

Adult↗

Lineage commitment of HLA-DR/CD38-defined progenitor cell subpopulations in bone marrow and mobilized peripheral blood assessed by four-color immunofluorescence.

We used four-color fluorescence analysis to compare lineage antigen expression in relationship to CD38 and HLA-DR on CD34+ progenitor cells in adult human bone marrow and mobilized peripheral blood. Each of four progenitor cell subpopulations defined by HLA-DR and CD38 intensity (CD38-/HLA-DR-, CD38-/HLA-DR+, CD38+/HLA-DR+, and CD38+/HLA-DR-) were present in both progenitor cell sources in similar ratios. The most prevalent subpopulation consisted of cells that expressed both CD38 and HLA-DR. Virtually all progenitor cells that lacked CD38 also lacked lineage antigens regardless of their HLA-DR expression. In contrast, the majority of the cells within both CD38+ progenitor cell subpopulations possessed either lineage antigens or the proliferation-associated antigen, CD71. Furthermore, CD71 was expressed on three times the number of CD38+/HLA-DR- cells when compared with the CD38-/HLA-DR- subpopulation. Within CD34+ progenitor cell subpopulations defined by the expression of CD38 and HLA-DR, the CD38+/HLA-DR- component appears to be the most mature, based on the expression of CD71 and various lineage-associated antigens, including representative markers characterizing early lymphoid, myeloid, and erythroid precursors. Thus, selection of the most immature CD34+ progenitor cells based solely on the lack of HLA-DR expression results in isolation of two distinct cell populations with markedly different maturation status and resultant growth characteristics.

ADP-ribosyl Cyclase↗

Differences in CD34+ cell subpopulations between human bone marrow and "mobilized" peripheral blood as determined with counterflow centrifugal elutriation.

Engineering of hematopoietic progenitor cells (HPCs) from bone marrow (BM) or "mobilized" peripheral blood (MoPB) is becoming increasingly important. Counterflow centrifugal elutriation (CCE) has been used to separate cells on the basis of their size. In this study, CCE was applied to evaluate BM and MoPB for differences in their HPC populations. Using a standard 4-mL elutriation chamber at 2300 rpm, CD34+ cells from BM peaked at a flow rate of 19 mL/minute, with 85% of all CD34+ cells recovered from fractions 15-22 mL/minute. The CD34+ cells from MoPB, mobilized with chemotherapy and granulocyte colony-stimulating factor (G-CSF), peaked at 22 mL/minute, with 90% of all CD34+ cells recovered from fraction 19-26 mL/minute. Colony-forming cells (colony-forming units granulocyte/macrophage [CFU-GM] + burst-forming unit-erythroid [BFU-E] + multipotent colony-forming units [CFU-GEMMs]) followed the distribution of CD34+ cells very closely, also with a shift to higher flow-rates for MoPB compared with BM. The lower flow-rate fractions of both BM and MoPB contained an increased proportion of CD34+ cells that did not express HLA-DR and/or CD38 on their surface, suggesting that the earliest CD34+ cells were enriched in the low-flow rate fractions. Although CFU-GMs, BFU-Es, and CFU-GEMMs from BM all peaked in the same fraction (19 mL/minute), high-proliferative potential colony-forming cells (HPP-CFCs) were concentrated in fraction 17 mL/minute, indicating that these earlier progenitor cells were slightly smaller. With MoPB, HPP-CFCs did not appear to be smaller than BFU-Es or CFU-GEMMs. CCE appears to be an attractive method for separating HPCs from BM or MoPB into populations of different maturity. Differences in CD34+ cell populations between BM and MoPB may help explain the differences in repopulation kinetics observed after transplantation.

Antigens, CD34↗

Nitric oxide has little effect on acute pulmonary hypertension and right ventricular function during acute respiratory distress syndrome.

OBJECTIVE: To evaluate the effect of nitric oxide (NO) on acute pulmonary hypertension and right ventricular function in patients with acute respiratory distress syndrome. DESIGN: A prospective clinical study. PATIENTS: Ten patients in the respiratory and surgical intensive care units were used. They met the criteria for acute respiratory distress syndrome and were significantly hypoxic. They were all ventilator-dependent at the time of the study. INTERVENTION: NO was delivered to the patients in 5, 10, 20 and 30 ppm doses for 30 minutes at each concentration. The dosing was not randomised. MEASUREMENTS AND RESULTS: The general and central haemodynamics were measured. Right ventricular function and interaction with the pulmonary artery impedance (Ea) were quantified with the ratio of right ventricular stroke work index/Ea. NO did not decrease the raised pulmonary artery pressure found in all of the patients. Right ventricular coupling to the circulation did not improve during the administration of NO. CONCLUSION: NO did not relieve the acute pulmonary artery hypertension associated with acute respiratory distress syndrome. As a consequence of this, right ventricular function failed to improve during the administration of NO.

Acute Disease↗

Predictive value for survival of soluble tumor necrosis factor receptors p55 and p75 during zidovudine-containing treatment in symptomatic human immunodeficiency virus type 1 infection.

Previous studies of asymptomatic human immunodeficiency virus (HIV) infection have shown that serum levels of soluble tumor necrosis factor receptors (sTNFR) are good predictors of disease progression and clinical outcome during zidovudine (ZDV) therapy. The present study of symptomatic HIV infection was designed to evaluate whether sTNFR p55 and p75 at weeks 0 (pretreatment) and 24 and 48 are predictors of death < or = 3 years after the start of ZDV 1,000 mg alone or combined with low-dose interferon-alpha (ZDV 500 mg + IFN-alpha 3 MIU three times weekly). CD4+ T-cell numbers and serum neopterin were analyzed in a similar way. Forty previously untreated symptomatic HIV-infected persons with CD4+ T-cell numbers > or = 150 x 10(6)/L were included. At baseline, in the nonsurvivor group, mean age (42.1 vs. 34.4 years, p = 0.002) and neopterin (24.7 vs. 18.0 nmol/L, p = 0.02) were higher, whereas mean CD4+ T-cell counts (202 vs. 295 x 10(6)/L, p = 0.02) were lower than in the survivors. All analyses were adjusted for age. For the pretreatment marker values, a significant relative risk (RR) for death was noted only in the univariate analysis for sTNFR-p55 > 1.7 ng/ml [RR 3.1; 95% confidence interval (CI) 1.1-8.8; p = 0.04]. During therapy, CD4+ counts < 200 x 10(6)/L at week 24 and 48 and neopterin > 20 nmol/ml at week 48 were independent predictors of survival in the uni- and multivariate analysis. Marker values relative to baseline were not predictive. sTNFR-p55 and p75 were of little use as surrogate markers for clinical efficacy during ZDV-containing drug regimens in symptomatic HIV-infected patients with CD4+ counts 150 x 10(6)/L.

Adult↗

Release of bactericidal/permeability-increasing protein in experimental endotoxemia and clinical sepsis. Role of tumor necrosis factor.

Bactericidal/permeability-increasing protein (BP]) is contained within the azurophilic granules of neutrophils and is able to neutralize endotoxin and kill Gram-negative bacteria. TNF has been implicated as a mediator of endotoxin-induced neutrophil degranulation. To assess the role of TNF in the elevated BPI levels during sepsis, the following studies were performed. 1) In 31 consecutive patients with sepsis syndrome, plasma BPI levels were markedly elevated compared with those in healthy controls, but showed no correlation with simultaneously measured TNF concentrations. 2) In four healthy men, i.v. injection of recombinant human TNF (50 microg/m2) induced a rapid rise in plasma BPI levels. 3) In eight normal subjects, i.v. administration of Escherichia coli endotoxin (4 ng/kg) elicited subsequent increases in the plasma concentrations of TNF and BPI. 4) Eight healthy chimpanzees were investigated after i.v. injection of endotoxin (4 ng/kg); four animals received endotoxin only, and four animals received an anti-TNF mAb simultaneously. Although anti-TNF completely prevented the endotoxin-induced appearance of TNF activity, the rise in BPI levels remained unaltered. These results suggest that TNF is not critical for the release of BPI from neutrophils during experimental endotoxemia or clinical sepsis.

Adult↗

Cytosolic inactivation of translocated neutrophil plasma membrane protein tyrosine phosphatase.

Phosphotyrosine phosphatases (PTPases) regulate cellular metabolic activation by reversing the effects of tyrosine kinases activated earlier in intracellular signaling pathways. We coupled fluorescence-activated cell sorter analysis using anti-CD45 monoclonal antibody with direct measurements of enzyme activity in resolved subcellular fractions to define mechanisms that potentially regulate the availability and activity of CD45-PTPase on neutrophil plasma membranes. Neutrophils in freshly obtained blood as well as neutrophils freshly isolated from blood were found to possess detectable levels of plasma membrane CD45 as assessed by immunofluorescence. However, plasma membranes from these cells were essentially devoid of PTPase catalytic activity, which was largely confined to the specific granules. Granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulated both the catalytic and antigenic components of CD45-PTPase on the plasma membrane of these cells. Upregulation was associated with a shift in the particulate subcellular PTPase catalytic activity from the specific granule fraction to the plasma membrane fraction. The tyrosine kinase inhibitor genistein abrogated GM-CSF-promoted upregulation of plasma membrane CD45 PTPase but did not prevent the GM-CSF-dependent decrease in specific granule catalytic activity. Anti-CD45 antibody immunoprecipitated PTPase activity from both specific granules of resting cells and plasma membranes of GM-CSF-treated cells. However, antiphosphotyrosine immunoprecipitated only activity that had translocated to the plasma membrane, suggesting a role for CD45 phosphorylation in translocation. Western analysis confirmed the tyrosine phosphorylation of CD45 in plasma membranes of GM-CSF-treated neutrophils. Preincubation of plasma membranes of GM-CSF-stimulated neutrophils with cytosol from resting cells resulted in a time- and temperature-dependent loss in membrane PTPase as a consequence of the effects of a cytosolic inactivator. Cytosol obtained from stimulated neutrophils possessed substantially reduced levels of this PTPase inactivator. We conclude that activity of the catalytic component of membrane PTPase in circulating neutrophils is regulated by a cytosolic inactivator. Upon stimulation, intact CD45 PTPase is incorporated into the plasma membrane by a process that requires tyrosine phosphorylation. As a result of inhibition of the cytosolic inactivator, the translocated PTPase expresses full activity, thereby amplifying the potential regulatory influence of the enzyme on the cells' functional response.

Antibodies, Monoclonal↗

Growth factor induction of cytosolic protein tyrosine kinase activity in human haemopoietic progenitor cells isolated by flow cytometry.

We employed a highly sensitive method to assay protein tyrosine kinase activity in extracts of subpopulations of CD34+ bone marrow progenitor cells isolated by fluorescence activated cell sorting in an attempt to better define how growth-factor induction of enzymatic activity relates to progenitor cell maturation. FACS analysis confirmed that, under the conditions employed, essentially all of the CD34+ cells in adult human marrow that lacked the CD38 antigen were devoid of the myeloid maturation marker CD33 as well as the lineage antigens: CD10, 13, 14, 15, 16, 19, 71 and glycophorin A. A variable portion (50-90%) of these CD34+, CD38- progenitor cells expressed HLA-DR. CD34+, CD38- cells that did not express HLA-DR were found to lack detectable levels of either membrane or cytosolic tyrosine kinase activity. HLA-DR+ progenitor cells that lacked CD38 possessed elevated levels of cytosolic tyrosine kinase activity but only low levels of plasma membrane activity. In contrast, CD34+ cells that expressed CD38 (and HLA-DR) possessed high levels of membrane-associated tyrosine kinase activity. A cocktail of haemopoietic growth factors that included IL-3, IL-6 and stem cell factor effectively induced tyrosine kinase activity in CD34+, CD38-, HLA-DR- progenitor cells. Growth factor induction of tyrosine kinase activity in these cells was not inhibited by actinomycin D or cyclohexamide. Most of the tyrosine kinase activity induced by these growth factors was recovered from the cytosolic fraction of disrupted cells. Thus, induction of cytosolic tyrosine kinase activity is an early event in the response of uncommitted haemopoietic cells to haemopoietic growth factors. Subsequent activation of membrane tyrosine kinases may initiate key transduction processes as these cells begin to differentiate.

Antigens, CD↗

Interleukin 10 release during endotoxaemia in chimpanzees: role of platelet-activating factor and interleukin 6.

Interleukin (IL-)10 has been demonstrated to inhibit endotoxin-induced production of a number of pro-inflammatory cytokines. The present study sought to compare the appearances in the circulation of IL-10, IL-6 and IL-8, and to assess the roles of endogenously produced platelet-activating factor (PAF) and IL-6 in IL-10 release during endotoxaemia in chimpanzees. Intravenous injection of endotoxin (lot EC-5, 4 ng/kg, n = 8) induced a transient rise in serum IL-10 concentrations, peaking after 2 h (213 +/- 70 pg/ml; P < 0.05). No correlations existed between peak IL-10 levels, and peak IL-6 and IL-8 levels. Neither infusion of the specific PAF antagonist TCV-309 (n = 4), nor infusion of a neutralizing anti-IL-6 monoclonal antibody (n = 4) influenced endotoxin-induced IL-10 release. IL-10 release elicited by injection of endotoxin is not mediated by PAF or IL6.

Animals↗

Impaired stem cell collection by consecutive courses of high-dose mobilizing chemotherapy using cyclophosphamide, etoposide, and G-CSF.

Tandem cycles of myeloablative chemotherapy can increase dose intensity and total dose of chemotherapy, but sufficient numbers of progenitor cells must be collected to ensure hematologic recovery after each treatment. This study was undertaken to determine if two courses of mobilizing chemotherapy given 4 weeks apart using cyclophosphamide 4000 mg/m2 and etoposide 400 mg/m2, combined with G-CSF 5-10 mg/kg on days 3-16 could each provide sufficient numbers of peripheral blood progenitor cells to support tandem cycles of myeloablative chemotherapy in 20 patients with stage IV breast cancer. Leukapheresis of blood with WBC > 1000/mm3 was performed daily for up to five collections (days 12-16), and mononuclear cells, CFU-GM, and CD34+ cells were compared between the first and second collections. The second course of mobilizing treatment resulted in similar numbers of mononuclear cells collected but far fewer CFU-GM and CD34+ progenitor cells. This prevented using the second collection of progenitor cells as the sole source for the second transplant. The data suggest that a second course of cyclophosphamide, etoposide, and G-CSF given 4 weeks after the first leads to progenitor cell depletion, and efforts to increase the yield of blood-derived progenitors should focus on the initial mobilizing procedure.

Adult↗

Immunomagnetic CD4+ and CD8+ cell depletion for patients at high risk for severe acute GVHD.

Acute GVHD remains a major problem in allogeneic BMT, in particular when donors other than HLA-identical siblings are used. To determine the efficacy of an immunomagnetic method for depletion of CD4+ and CD8+ lymphocytes from the marrow graft, a series of 15 patients was studied. Thirteen patients had matched unrelated donors, and two patients had related donors. Cyclosporine was used as GVHD prophylaxis in combination with CD4+ and CD8+ depletion, which removed 94.1 +/- 3.2%, 97.0 +/- 5.1%, and 96.7 +/- 3.1% of CD3+, CD4+ and CD8+ cells, respectively. All patients engrafted promptly with AGC > 500/mm3 after a median of 16 days post-BMT. Acute GVHD grade II-IV developed in 0/2 related transplants and 4/13 MUD transplants; only one patient had grade III-IV acute GVHD. No late graft failure was observed. Three patients relapsed; two had advanced disease at the time of BMT. Seven patients are alive and in CCR after a median of 497 days; actuarial survival is 39% at 24 months. The fever syndrome observed with selective CD8+ cell depletion was not seen with the combined CD4+ and CD8+ cell depletion. Immunomagnetic CD4+ and CD8+ cell depletion of marrow grafts, in combination with in vivo cyclosporine, is a simple, reproducible and effective method to decrease the incidence and severity of acute GVHD in patients at high risk for this complication after allogeneic BMT.

Acute Disease↗

[Experience with chronic hemodialysis in diabetic patients with kidney failure].

Between 1978 and 1992, 534 patients--including 35 (25 IDDM and 10 NIDDM) diabetics--were accepted to chronic hemodialysis (HD) at our Dialysis Center. The 1-year cumulative survival rate (CSR) was significantly lower in diabetic vs. non-diabetic group (66 +/- 8% vs. 78 +/- 2%), p < 0.05). At the onset of diabetes the mean age of IDDM patients vs. NIDDM patients was 18.2 +/- 2.7 years vs. 51.3 +/- 3.1 years, respectively. At the beginning of HD treatment the mean age of IDDM patients vs. NIDDM patients was 38 +/- 2.4 years vs. 58.3 +/- 2.6 years. In IDDM group until the start of HD treatment the mean duration of diabetes was 20 +/- 1.3 years and it did not depend on the quality of preuraemic metabolic control (p = 0.825); mean duration of diabetes until their death was 22.5 +/- 1.3 years. Mean age of IDDM and NIDDM patients at their death was 38.8 +/- 3 years and 60.5 +/- 3.7 years. Average duration of HD treatment was 16 +/- 2.5 months in IDDM group and 21.5 +/- 5.8 months in NIDDM group. Major causes of death were cardiovascular complications of diabetes (39%) and infections (33%). We found no difference in CSR related to gender, age, type of diabetes, quality of metabolic control during the HD treatment, but CSR was significantly higher in patients with good metabolic control from the onset of diabetes (1-year CSR of adequately vs. poorly controlled diabetics: 80% vs. 62%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The acute promyelocytic leukaemia-associated PML gene is induced by interferon.

The PML protein concentrates within discrete nuclear structures known as nuclear bodies, also called NDs or PODs, which contain several proteins including the interferon (IFN)-inducible SP100 product. The function of these structures remains elusive. We and others have shown recently that they represent specific targets for adenovirus and herpes simplex virus. This prompted us to investigate whether PML, like SP100, might be induced by IFN and to explore the role of PML in viral infection. Here we report that PML mRNA levels increase rapidly in response to interferon treatment. This accumulation of PML transcripts is a primary IFN response since it does not require de novo protein synthesis. The IFN-induced activation of the PML gene is accompanied by enhanced protein expression as revealed by immunolabelling. Both the intensity of the staining and the number of labelled structures increased upon interferon exposure. To probe the role of PML in IFN action, we compared the antiviral state established by alpha-interferon in embryonic fibroblasts (EFs) derived from null mutant mice for PML and from wild-type control mice. The resistance to viral infection conferred by IFN-alpha was identical in both PML+/+ and PMLm/m fibroblasts indicating that PML is not an essential mediator of the antiviral effect of interferon. We also noted that DNA-binding factors are normally activated by IFN in PMLm/m cells.

Base Sequence↗

Observed behavior of patients with seasonal affective disorder and an interviewer predicts response to light treatment.

We investigated whether observable behavior of seasonal affective disorder (SAD) patients and an interviewer during an interview before light treatment is related to the response to the light treatment. Different observed behavioral elements of 24 SAD patients and of 2 interviewers, assessed before light treatment, were reduced to "behavioral factors." Forward multiple regression analyses were applied to investigate whether these factors might predict the response to light therapy (3 h of bright light between 09:00 and 12:00 h or between 18:00 and 21:00 h on 5 consecutive days). In addition, it was investigated whether the interviewers' factors could be predicted from the patients' factors. Both patients' and interviewers' factors predicted the response to light treatment. Response-related factors of patients and interviewers were interrelated. The results suggest that behavioral processes may play a role in the mechanisms underlying the response to light treatment in SAD. They support the relevance of interpersonal theories in seasonal depression.

Adult↗

Phorbol ester-induced priming of superoxide generation by phosphatidic acid-stimulated neutrophils and granule-free neutrophil cytoplasts.

This study was undertaken to examine the mechanisms involved in polymorphonuclear leukocyte superoxide release stimulated by exogenous phosphatidic acid (PA). Unlike the immediate burst of superoxide release affected by membrane-permeable dioctanoylglycerol (DiC8-DAG), dioctanoyl phosphatidic acid (DiC8-PA) induced superoxide release after a lag period of 5-20 min. This period was considerably reduced or eliminated when cells were primed by substimulatory levels of phorbol myristate acetate (PMA). Granule-depleted neutrophil cytoplasts also responded to DiC8-PA with a burst of superoxide generation. Activation of the cytoplast superoxide generating system in response to DiC8-PA was also significantly faster after cells had been preexposed to substimulatory levels of PMA, indicating that at least a portion of the priming mechanism was independent of PMA-induced degranulation. To further examine the potential mechanism of PMA priming of responses to PA, we evaluated the activity of neutrophil ecto-phosphatidic acid phosphohydrolase (ecto-PA phosphohydrolase), which generates diacylglycerol from exogenous PA. PMA priming had no discernable effect on the activity of this enzyme. In addition, propranolol, an inhibitor of PA phosphohydrolase, did not selectively inhibit PMA priming of neutrophil responses to DiC8-PA, indicating that priming did not result from acceleration of DiC8-PA hydrolysis. We therefore investigated the possibility that activation of protein kinase C was the basis of the primed response. Several semiselective protein kinase C inhibitors (calphostin C, H-7, and acylmethylglycerol) inhibited DiC8-DAG- and DiC8-PA-induced superoxide release as well as PMA-primed responses to approximately the same extent. These results are consistent with the hypothesis that neutrophil responses to phosphatidate are mediated by diglyceride generated by the action of ecto-PA phosphohydrolase. PMA priming does not result from increased catalytic activity of ecto-PA phosphohydrolase but rather seems to result from potentiation of an intermediate involved in the cells' response to multiple stimuli.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Inhibition of the release of soluble tumor necrosis factor receptors in experimental endotoxemia by an anti-tumor necrosis factor-alpha antibody.

The role of tumor necrosis factor-alpha in the shedding of soluble tumor necrosis factor receptors in endotoxemia was investigated. The appearance of the soluble tumor necrosis factor receptors was assessed in four healthy volunteers following an intravenous injection of tumor necrosis factor-alpha and in eight chimpanzees after intravenous administration of endotoxin in the absence or presence of concurrent treatment with a neutralizing anti-tumor necrosis factor-alpha monoclonal antibody. Injection of tumor necrosis factor-alpha in humans elicited a significant, instantaneous (after 15 min) increase in the plasma concentrations of both types of soluble tumor necrosis factor receptors. In chimpanzees, treatment with the anti-tumor necrosis factor-alpha antibody completely neutralized endotoxin-induced tumor necrosis factor-alpha activity. The release of soluble tumor necrosis factor receptors was strongly (80-90%) inhibited in the presence of the neutralizing antibody. Our results indicate that tumor necrosis factor-alpha is a prime mediator of endotoxin-induced release of its own soluble receptors.

Adult↗