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Biomedical subjects

L Jensen

Publications and source records attributed to L Jensen.

At least 37 records · Page 2Linked to original sources
PubMed2000

CD68+/CD83+/CD1a- dendritic cell subsets from patients with multiple myeloma are not infected with human herpesvirus 8.

Recently, a subset of dendritic cells with the phenotype CD68+/CD83+/CD1a-, present in patients with multiple myeloma (MM), was reported to be infected with human herpesvirus 8 (HHV-8). Therefore we wished to clarify whether HHV-8 infection might be related to the pathogenesis of MM. In an attempt to identify HHV-8 infected cells in patients with MM, long-term bone marrow cultures from 8 MM patients and dendritic cell cultures from 11 MM patients were established. In addition, fresh bone marrow aspirates from 10 MM and 10 patients with monoclonal gammopathy of undetermined significance (MGUS) were included in the study. All samples were analysed by a sensitive semi-nested PCR assay and were found to be consistently PCR negative. Phenotyping of day 7 dendritic cell cultures demonstrated the presence of a sufficient number of CD68+/CD1a- and CD83+/CD1a- cells. However, to exclude the presence of infrequent HHV-8 infected cells, the CD68+/CD1a- subset from 3 dendritic cell cultures was sorted in numbers of 105 for each PCR test, and again a negative PCR result was observed. This study documents that the CD68+/CD83+/CD1a- dendritic cells in patients with MM are not generally infected with HHV-8 and, as a consequence, it is unlikely that HHV-8 plays a role in the pathogenesis of MM.

Antigens, CD↗
PubMed2000

Control of the classical and the MBL pathway of complement activation.

The activation of complement via the mannan-binding lectin (MBL) pathway is initiated by the MBL complex consisting of the carbohydrate binding molecule, MBL, two associated serine proteases, MASP-1 and MASP-2, and a third protein, MAp19. In the present report we used an assay of complement activation specifically reflecting the physiological activity of the MBL complex to identify biological and synthetic inhibitors. Inhibitor activity towards the MBL complex was compared to the inhibition of the classical pathway C1 complex and to a complex of MBL and recombinant MASP-2. A number of synthetic inhibitors were found to differ in their activities towards complement activation via the MBL pathway and the classical pathway. C1 inhibitor inhibited both pathways whereas alpha2-macroglobulin (alpha2M) inhibited neither. C1 inhibitor and alpha2M were found to be associated with the MBL complex. Upon incubation at 37 degrees C in physiological buffer, the associated inhibitors as well as MASP-1, MASP-2, and MAp19 dissociated from MBL, whereas only little dissociation of the complex occurred in buffer with high ionic strength (1 M NaCl). The difference in sensitivity to various inhibitors and the influence of high ionic strength on the complexes indicate that the activation and control of the MBL pathway differ from that of the classical pathway. MBL deficiency is linked to various clinical manifestations such as recurrent infections, severe diarrhoea, and recurrent miscarriage. On the other hand, impaired control of complement activation may lead to severe and often chronically disabling diseases. The results in the present report suggests the possibility of specifically inhibiting of the MBL pathway of complement activation.

Animals↗
PubMed2000

Comparison of the nutritional composition of diets of persons with fecal incontinence and that of age- and gender-matched controls.

PURPOSE: In our clinical and research experience, persons with fecal incontinence anecdotally report altered diet intake to avoid incontinence. The purpose of this study was to compare the dietary intake of 39 persons with fecal incontinence living in the community with that of age- and gender-matched control subjects who had normal bowel function. The diets of both groups were compared with recommended dietary allowances (RDAs) for their constituent nutrients. METHODS: Subjects prospectively recorded the type, amount, and method of preparing all foods and beverages ingested for 8 consecutive days. Diet records were analyzed using the Nutritionist IV software program. MAIN OUTCOME MEASURES: The main outcome measures were the amounts and percentage of the RDAs of macronutrients and micronutrients in the subjects' diets. RESULTS: There were no significant differences in the intake of total kilocalories, protein, fat, dietary fiber, caffeine, or lactose by the fecal incontinence and control groups. The fecal incontinence group had a greater intake of carbohydrates, manganese, and vitamin B(1) compared with the control group. Diets of both groups exceeded 100% of the RDA for protein, phosphorus, iron, sodium, potassium, Vitamins B(1), B(2), B(3), B(12), and C and folate. Diets of both groups had less than 50% of the RDA for biotin, chromium, copper, and manganese but did not differ significantly. The percentages of the RDA for calcium and vitamin D were 84% +/- 6% and 56% +/- 8% for the fecal incontinence group and 90 +/- 8 (P =.6) and 69 +/- 11 for the control group (P =.4). CONCLUSIONS: The diets of persons with fecal incontinence were similar to those of control subjects with normal bowel function. Both the fecal incontinence and control groups may improve their nutritional patterns by lowering sodium and protein intake and increasing dietary fiber and monounsaturated fat intake. Calcium and vitamin D supplementation may improve dietary deficiencies and lower disease risks. Including a nutritional assessment and consultation in the care of persons with fecal incontinence to improve their general health and prevent disease is recommended, but consideration must be given to altered diet patterns perceived by the patient to prevent fecal incontinence.

Case-Control Studies↗
PubMed2000

A new model for evaluation of thrombosis and ischaemia/reperfusion injury.

BACKGROUND: The purpose of the present study was to describe infarct size and platelet accumulation when reperfusion injury was combined with a thrombogenic lesion in the coronary artery. The left anterior descending artery was damaged in 11 pigs and subsequently occluded proximal to the lesion for 50 min, followed by 4 h of reperfusion. RESULTS: The infarct size/area at risk was 40 (35 63)%. Infarct size correlated with troponin-T-3 h (p=0.85, p<0.002), but not with creatine kinase-3 h. Platelet aggregation decreased by 34% (p<0.01) at 15 min of reperfusion, but returned to baseline. Platelet accumulation in the left ventricle was significantly higher in the area at risk (194 (157-206)%) compared to the right ventricle (137 (120-142)%); p<0.05). CONCLUSION: A decreased platelet reactivity and increased accumulation of platelets in the area at risk indicates that activated platelets become entrapped in the myocardium. Troponin-T was a better marker of myocardial damage than creatine kinase in this in vivo model with pigs.

Animals↗
PubMed2000

A comparative study of sequential priming and mobilisation of progenitor cells with rhG-CSF alone and high-dose cyclophosphamide plus rhG-CSF.

Stem cell mobilisation can be achieved either by administration of rhG-CSF alone or after high-dose cyclophosphamide (HDCy) plus rhG-CSF. We have compared both mobilisation procedures intra-individually in 43 patients with haematological malignancies. Furthermore, the toxicity data were registered. The CD34+ cell yield was higher after mobilisation with HDCy plus rhG-CSF than after rhG-CSF alone in 21 out of 22 patients who were actually harvested after both procedures. If a patient mobilised insufficiently after rhG-CSF alone, the yield of CD34+ cells after the following HDCy priming was lower compared to patients who mobilised sufficiently after rhG-CSF priming alone. In 12 patients with B cell malignancies a reduced number of B cells such as CD10+, CD19+, CD20+ cells in bone marrow as well as in leukapheresis products was observed after HDCy plus rhG-CSF compared to rhG-CSF alone. Toxicity data revealed HDCy as a relatively toxic priming regimen with all patients hospitalised and 74% experiencing neutropenic fever and administration of intravenous antibiotics. In two patients, seizure-like episodes were observed during cyclophosphamide bolus infusion. In conclusion, HDCy increased the yield of CD34+cell and reduced B cells in leukapheresis products indicating reduced tumour cell load compared with rhG-CSF priming alone. The efficacy of HDCy priming is limited by its profound toxicity and morbidity. Studies evaluating efficacy and safety of lower doses of cyclophosphamide are needed. Bone Marrow Transplantation (2000) 26, 717-722.

Adolescent↗
PubMed2000

Immunopathology of in situ seminoma.

In this study of the seminomatous human testis the composition, activity and apoptosis of lymphocytes infiltrating the immune-privileged seminiferous tubules with in situ seminoma were studied by immunohistochemistry and DNA fragmentation detection. Likewise the lymphocytes infiltrating the invasive seminomas were studied. The study showed equal numbers of CD4+ and CD8+ T cells and B cells, about 30% of the cells. Very few T gamma/delta and NK cells were present. The activity in terms of IL-2-R, FasL and perforin expression was low. Apoptosis of the lymphocytic cells was limited. No differences were observed between the lymphocytes in seminiferous tubules with in situ seminoma and the lymphocytes in invasive tumours. The study suggests that either specifically committed lymphocytes are not present or, if present, immune-suppressing mechanisms in addition to FasL may be working.

Apoptosis↗
PubMed2000

Testing of the Incontinence Impact Questionnaire (IIQ-7) with men after radical prostatectomy.

OBJECTIVE: The objective of this study was to test the validity and reliability of the Incontinence Impact Questionnaire (IIQ-7), a 7-item self-report instrument designed to assess the impact of urinary incontinence (UI), in men. SUBJECTS: Fifty-eight men with incontinence after radical prostatectomy were the subjects of the study. METHODS: Content validity was assessed by a panel of experts. Construct and criterion validity were examined with 3 groups of men who had UI in a randomized controlled trial comparing pelvic muscle exercises with pelvic muscle exercises plus electrical stimulation. Internal consistency and stability coefficients for the IIQ-7 were determined. RESULTS: The content validity index was 0.88. Four items were below the designated content validity index level. A 2-factor analysis solution (factor I-impact on daily activities; factor II-emotional impact) explained 84.94% of the variance. No significant group differences were recorded on impact of UI (F = 0.37, P =.70), nor were any differences among subjects found over time (F = 0.90, P =.50). A positive relationship was found between grams of urine loss on a 24-hour pad test and IIQ-7 scores (r = 0.34, P =.003 to.51, P =.001). When the IIQ-7 score decreased, self-reported quality of life improved as measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Version 2 (r = -0.57, P =.0001 to -.49, P =.001). A strong relationship was found between responses to the question "Does leakage affect your life?" and the IIQ-7 scores. Internal consistency ranged between 0.88 and 0.92. IIQ-7 scores were consistent when urine loss was stabilized between 16 and 24 weeks after entry into the study (r = 0.89, P =.0001). CONCLUSION: The IIQ-7 is a reliable measure of the impact of UI; however, the scale requires additional testing regarding construct validity in men.

Activities of Daily Living↗
PubMed2000

The clonal hierachy in multiple myeloma.

In this report we evaluated the number and phenotype of blood circulating B-cell subsets at different stages of differentiation in 26 patients with newly diagnosed multiple myeloma (MM). In all patients, plasma cells and/or plasma blasts could be identified by flow cytometry with a mean frequency of 1.20% and 0.07%, respectively. In 76.9% of the patients these cells showed aberrant expression mainly of CD56, CD28 and CD117, none of these markers were found on the earlier B-lymphocytes. Clonal B-cells preceding the plasma blast stage were identified by patient specific IgH RT-PCR on sorted B-cell subsets. The clonal cells included the less differentiated CD38+ CD19+ and CD38-/CD19+ subsets. illustrating that the clonal cells are part of an ongoing differentiation process. Further, the presence of CD38-/CD19+ cells with somatically mutated Cgamma transcripts identical to the tumor-specific Calpha transcript, shows that the clonal hierarchy in myeloma may include memory B-cells.

ADP-ribosyl Cyclase↗
PubMed2000

Work history and U.S. elders' transitions into poverty.

Poverty risks among elders are shaped in critical ways by their work history, demographic characteristics, current marital status, and residential context. Using 25 years of data from the Panel Study of Income Dynamics, we combined past occupation and work history of elders and their spouses with information on current marital status and residence to estimate discrete time event history models of first transitions into poverty after reaching age 55. Education, work history, and preretirement wages contributed to men's and some women's probability of becoming poor. Work history remained an important predictor of transitions into poverty, even after controlling for preretirement wages and human capital. Metropolitan residence was associated with a lower probability of making transitions into poverty. This residential difference was not appreciably attenuated in three of four elderly subgroups after measures of work history, preretirement wages, current life events, and demographic characteristics of the elders were included in the models.

Aged↗
PubMed2000

Living with change: elderly women's perceptions of having a myocardial infarction.

The purpose of the study described in this article was to explore and describe elderly (70+ years) women's perceptions of having a myocardial infarction (MI). Structured and unstructured, open-ended, face-to-face interviews with 11 women were used to collect qualitative data. The central theme that emerged was living with change. Five phases were revealed: searching for a diagnosis, being hit with the reality, discovering the nature of the change, adjusting to the change, and moving on with the change. Throughout these phases, the women were faced with the challenges of being in control, managing uncertainty, making sense, being independent, and sheltering others. The continuous process of change in their lives was taken for granted by these women. By having an understanding of the perspective of elderly women who have an MI, nurses will be more effective when caring for these individuals.

Adaptation, Psychological↗
PubMed1999

Reduced bone marrow stem cell pool and progenitor mobilisation in multiple myeloma after melphalan treatment.

The content of stem cells was analysed in bone marrow samples from 75 multiple myeloma patients. In unstimulated bone marrow the percentage of CD34+ cells was significantly reduced in 11 patients previously treated with melphalan-prednisolone (MP)(median= 0.15%) compared to median 0.87% in 31 untreated patients (P=0.0001). The bone marrow cellularity in the two groups did not differ. There was no correlation between the number of courses or total dose of melphalan and content of CD34+ cells in the bone marrow. The clonogenicity as well as the ability to expand the marrow stem cell pool during growth factor treatment were also reduced in MP treated patients compared to untreated patients. Analysis of different subsets of CD34+ cells revealed no influence on the pre B cell compartment in the bone marrow by MP treatment, but the committed stem cells (CD34+CD38+) were reduced more than the uncommitted stem cells (CD34+CD38-) in the MP treated group compared to the untreated patients. Mobilisation to and harvest of total number of CD34+ cells from peripheral blood was also reduced in the MP treated group. There was, however, no difference in the distribution between CD34+CD38+ and CD34+CD38- populations in the leukapheresis products in the untreated and the melphalan-treated group, suggesting selective mobilisation of CD34+CD38+ cells and/or differentiation of CD34+CD38-cells during growth factor stimulation. We conclude that melphalan decreased the number of stem cells in the bone marrow, the ability to expand the stem cell pool and mobilise stem cells to the pheripheral blood.

Adult↗
PubMed1999

Pathogenicity of selected Toxoplasma gondii isolates in young pigs.

The pathogenicity in 7-week-old pigs to five different Toxoplasma gondii strains of various host species origin was compared after i.v. inoculation of 10(4) tachyzoites. Additionally, one group of pigs was inoculated i.v. with 10(6) tachyzoites of the reference strain, SSI 119. In response to the infection a significant effect of T. gondii tachyzoite inoculation dose as well as differences among strains could be observed in several parameters. The 10(6)-dose inoculated pigs showed variable degrees of clinical illness and recurrent episodes of fever 4-17 days p.i., while pigs of four of the 10(4) tachyzoite inoculated groups experienced a short-lived rise in body temperature from day 6-8 p.i. without any apparent illness or inappetence. Control pigs and pigs infected with the least pathogenic strain had normal body temperature throughout the experiment. In all inoculated pigs, T. gondii-specific IgM and IgG antibodies appeared from day 8-10 and 10-17 p.i., respectively. Serum levels of alkaline phosphatase and the acute phase protein haptoglobin were decreased or increased, respectively, in response to the infection. Differential leukocyte count on peripheral blood revealed a significant lymphocytopenia on day 6 p.i. equal to both CD4+ and CD8+ T-cells, but shifting towards a reduced ratio of CD4+/CD8+ T-cells from day 8-14 p.i. In the 10(6)-dose inoculated pigs a considerable increase in zymosan induced and spontaneous oxidative burst capacity of peripheral blood leukocytes was observed from 6 days p.i. compared with control pigs. Oxidative burst capacity was not examined for other pigs. In conclusion, several useful parameters to identify differences in T. gondii pathogenicity other than mortality were identified. Furthermore, even at low doses, significant differences between recently collected Danish T. gondii field isolates were demonstrated after i.v. inoculation in young pigs.

Alkaline Phosphatase↗
PubMed1999

Comparison of the IFAT and Iscom-ELISA response in bovine foetuses with Neospora caninum infection.

The study was carried out to evaluate the efficacy of foetal serology in the diagnosis of Neospora-associated bovine abortions. Fluids from 14 foetuses of cows with confirmed neosporosis (Group A), seven foetuses with confirmed bovine viral diarrhoea virus (BVD infection) (Group B) and 11 aborted foetuses without demonstrable infection (Group C) were examined. The age of the foetuses ranged from 4.5 months to 9 months. Albumin concentration (measured by Rocket Immunoelectrophoresis) was not significantly different in Group A compared with that in both Groups B and C, while that in Group B was significantly lower than in Group C. Levels of total IgG ranged from 0.01 to 1.78 (mg IgG) ml(-1) measured by single radial immunodiffusion technique. A measurable level of total IgG was found in all foetuses from Groups A and B, with no significant difference between levels in the two groups. Only one foetus in Group C had a detectable level of IgG. All foetuses in Group A had a specific IgG response (titre> or = 20) against Neospora caninum using the IFAT, while no positive responses in IFAT were found in Groups B and C. Measurement of specific IgG1 and IgG2 by Iscom-ELISA showed one and three false-negative results, respectively, in Group A. The IgG1 and IgG2 response in Group A was correlated according to the Spearman test (r = 0.66). Increasing age of the foetuses correlated significantly with the foetal IgG concentration, the specific IgG and IgG1 + IgG2. On the basis of the results obtained, it was concluded that the IFAT with a cut-off titre of 1:20, was a specific method for diagnosis of neosporosis in foetuses older than 4.5 months. The Iscom-ELISA also showed promising results as a method for screening specific antibodies against N. caninum in foetal fluid.

Abortion, Veterinary↗
PubMed1999

Comparison of subjective classification of stool consistency and stool water content.

OBJECTIVE: The purpose of this study was to compare the stool consistency categorizations made by 39 adults with fecal incontinence and the percentage of water in their stools determined by lyophilization. METHODS: Subjects collected all stools daily for 8 days during a baseline period and at the end of a fiber treatment period. Stool consistency was recorded as hard and formed, soft but formed, loose and unformed, or liquid. Aliquots of the stools were lyophilized to constant weight. MAIN OUTCOME MEASURES: The main outcome measures were the percentage of stool water among stools in each consistency category and the correlation between subjects' stool consistency categorizations and the percentage of stool water. RESULTS: The subjects were 8 men and 21 women, ranging in age from 30 to 89 years, who were participating in a study of the effectiveness of dietary fiber for treating fecal incontinence. A total of 1023 stool samples were analyzed. Significant differences in the mean percentage of water were found among the 4 stool consistency categories (hard and formed = 68% +/- 0.9%, soft but formed = 74% +/- 0.3%, loose and unformed = 80% +/- 0.4%, and liquid = 85% +/- 0.3%; P < .001). Ninety-six percent of the stools had a percentage of water within 2 SDs of the mean percentage of water of other stools in their consistency category. CONCLUSION: This classification system of stool consistency is a valid and practical measure for clinical studies. It may be useful for clinicians and patients to evaluate outcomes of treatments directed at improving stool consistency.

Adult↗
PubMed1999

Selective loss of progenitor subsets following clinical CD34+ cell enrichment by magnetic field, magnetic beads or chromatography separation.

In this preclinical evaluation we have compared the efficacy of three clinical CD34+enrichment procedures with respect to purity, yield and recovery, as well as risk of selective loss of CD34+ lineage-specific subsets. The three devices work by different principles and have several different manipulation steps: The magnetic field separator uses paramagnetic iron-dextran particles; the magnetic microbead selection is based on the advantage of a large surface area for immobilisation of the monoclonal antibody within a very small volume; the original immunoabsorption technique is based on the use of biotinylated antibody applied to a column of avidin-coated sephadex beads. The results of this evaluation gave a median purity 96% (88-98%), 86% (62-97%), and 49% (18-85%), and median yield of 65% (54-100%), 40% (21-74%), and 30% (8-55%), respectively. Subset analysis recognised a selective loss of CD34+/61+ after enrichment, most likely due to class I-II antibodies used for the enrichment step or, alternatively, nonspecific binding of megakaryocytic progenitors. Tumour cell spiking experiments on a clinical scale documented an expected 2-4 log reduction resulting in a number of potentially malignant cells in the CD34 enriched product. Our data support four major conclusions: First, that magnetic field separation is superior to magnetic beads and chromatography selection, mainly due to the risk of cell loss and insufficient recovery with the two latter methods. Second, that late differentiated progenitors with CD34 class III epitopes present are lost during the enrichment procedures. The third major conclusion is that chromatography selection results in a selective loss of CD34bright cells, which are most likely uncommitted early progenitors. This was an unexpected finding which may be a consequence of an imbalance between the strong forces between biotin-avidin and insufficient physical manipulation for CD34+ cell release. Finally, the data document that CD34 selection alone is an inappropriate way to eliminate tumour cells due to the uncontrolled variables and the inconsistent outcome. The only products which can be expected to be purged free of tumour cells are the ones with very minimal (<10-5) contamination in the starting products, ie products documented tumour free with the most sensitive techniques for quantitation. If this is not the case, the optimal purging strategy may be a two-step procedure including CD34 selection and subsequent depletion of the tumour cells in question.

Antigens, CD34↗
PubMed1999

Circulating clonal cells in multiple myeloma do not express CD34 mRNA, as measured by single-cell and real-time RT-PCR assays.

The peripheral blood (PB) mononuclear cells in patients with multiple myeloma (MM) have been reported to include CD34-expressing cells that are clonally related to the myeloma cells. To determine whether there were elevated levels of CD34 mRNA or whether CD34+ cells in the PB include myeloma-related cells, we developed a quantitative real-time and a competitive CD34 RT-PCR assay working on single flow-sorted cells. Myeloma-specific cells were detected with allele-specific oligonucleotides (ASO) IgH PCR. PBSC products and mononuclear cell fractions in blood from normal donors, untreated and treated myeloma patients were analysed. When measured by flow cytometry, the numbers of CD34+/CD19+ cells were consistently < 0.1% of the mononuclear cells. In addition, no significant difference was found in the levels of CD34 mRNA between normal subjects and untreated MM patients (P = 0.935). In the treated group of MM patients the CD34 mRNA levels were significantly reduced (P = 0.052) because of the stem cell toxicity of melphalan. Further, no cells clonally related to the MM clone were found within the CD34 compartment, defined by a sort-gate that included all cells expressing CD34 mRNA, as no cells outside the used CD34 sort-gate had a detectable level of CD34 mRNA. We conclude that in myeloma patients, the myeloma clone is not found within the CD34 compartment.

Antigens, CD34↗
PubMed1999

Fas and Fas-ligand expression in seminomatous testes.

Sixteen seminomas with surrounding tissue containing normal and precancerous (cis) seminiferous tubules were examined for the expression of Fas (CD95, APO-1) and Fas ligand (FasL) (CD95L). This was done by analyzing frozen specimens using immunohistochemistry with antibodies directed against Fas and FasL. The study showed that varying numbers (mean approx. 20%) of Fas-positive lymphocytes were present among tumor-infiltrating lymphocytes, but very few FasL-positive lymphocytes. Fas was not expressed by normal seminiferous tubules and only occasional Fas-positive epithelial cells were seen in cis tubules. FasL was expressed in 9 out of 10 cases in virtually all normal seminiferous tubules, mainly as a thin layer at the base of the seminiferous epithelium. In precancerous tubules, this layer was discontinuous and less pronounced. Rete testis expressed FasL in 2 out of 2 cases with rete present and Fas in 1 out of 1 case. Invasive tumor cells did not express Fas or FasL. The data are discussed in relation to immune reactions to seminomas and to the concept of the testis being an immunologically privileged area.

Antigens, Neoplasm↗