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Biomedical subjects

A Ost

Publications and source records attributed to A Ost.

At least 19 recordsLinked to original sources
PubMed2006

Down-regulation of interferon-gamma parallels clinical response to selective leukocyte apheresis in patients with inflammatory bowel disease: a 12-month follow-up study.

BACKGROUND & AIMS: Pilot studies have indicated a therapeutic role for an apheresis device (Adacolumn) that selectively adsorbs leukocytes in patients with inflammatory bowel diseases. It may also exert immunoregulatory effects contributing to its clinical efficacy. This study aimed to correlate the clinical response to leukocyte apheresis with the expression of key cytokines in mucosal tissue, in peripheral leukocytes, and in plasma. METHODS: Ten patients (seven with Crohn's disease and three with ulcerative colitis, median age: 31 years) with mild to moderately chronic activity were recruited to an open study. Patients were refractory to or had a relapse despite conventional treatment including azathioprine. Leukocyte apheresis was performed once a week for five consecutive weeks. Clinical efficacy was assessed on week 7 and after 12 months. Colonoscopy with multiple biopsies was performed at the start of the study and after 7 weeks for semiquantitative immunohistochemical analyses of cytokines. Cytokine levels in blood and the proportion of cytokine producing CD4+ and CD8+ lymphocytes were determined. RESULTS: The apheresis procedures were well tolerated and no major adverse events were encountered. The median clinical activity score decreased from 12 to 7 on week 7 (P=0.031, n=9) and to 4 after 12 months (P=0.004, n=9). Five patients were in clinical remission at the 12th month. Tissue interferon (IFN)-gamma-positive T-cells decreased in clinical responders (P=0.027) after apheresis. In parallel, significantly lower levels of IFN-gamma-producing lymphocytes were detected in peripheral blood. IFN-gamma-positive cells in pretreatment biopsies completely disappeared or decreased in posttreatment biopsies sampled on week 7 in responders (P=0.027) and appeared to predict the maintenance of long-term remission or response after 12 months. CONCLUSIONS: Leukocyte apheresis is a novel and safe nonpharmacological adjunct therapy that may prove useful in steroid refractory or dependent patients when conventional drugs have failed. Down-regulation of IFN-gamma in mucosal biopsies and in peripheral leukocytes may be a predictive marker for sustained, long-term response.

Adult↗
PubMed2005

Dynamics of mucosal permeability and inflammation in collagenous colitis before, during, and after loop ileostomy.

Collagenous colitis has become a more frequent diagnosis but the aetiology of this disease is still unknown. We describe a female patient with intractable collagenous colitis who was treated with a temporary loop ileostomy. She was followed clinically, histopathologically, and functionally by measuring mucosal permeability before surgery, after ileostomy, and after bowel reconstruction. In our case report, active collagenous colitis was combined with increased transcellular and paracellular mucosal permeability. Diversion of the faecal stream decreased inflammation of the mucosa and normalised epithelial degeneration and mucosal permeability. After restoration of bowel continuity, mucosal permeability was altered prior to the appearance of a collagenous layer.

Colitis↗
PubMed2003

Laminin 5 gamma 2 chain expression: a marker of early invasiveness in colorectal adenomas.

AIM: Polyps of the colon and rectum are considered to be premalignant lesions in the development of colorectal cancer. However, knowledge of how normal epithelial cells gain invasive properties is limited. Laminin 5 gamma 2 chain expression was investigated to determine the role of laminin 5 as a marker of potential invasiveness in colorectal polyps. MATERIAL/METHODS: Sixty seven polyps of different types (15 hyperplastic polyps, 12 serrated adenomas, 16 tubular adenomas, and 24 adenomas with a villous component) were assessed for gamma 2 chain expression of laminin 5 by immunohistochemistry on archival, paraffin wax embedded sections. RESULTS: Ten polyps stained positive and the number of polyps expressing the laminin 5 gamma 2 chain increased significantly as the phenotype of the adenomas became more atypical: none of the 15 hyperplastic polyps, two of the 16 tubular adenomas (12.5%), and six of the 24 adenomas with a villous component (25%) were positive. Two of 12 (17%) serrated adenomas, regarded as a distinct form of colorectal neoplasia, showed gamma 2 chain expression. Furthermore, laminin 5 gamma 2 chain expression correlated with lesion size. Polyps smaller than 10 mm expressed the gamma 2 chain less frequently than did those equal to or larger than 10 mm. CONCLUSION: Laminin 5 gamma 2 chain expression was found to increase progressively towards a more atypical phenotype of adenoma. The results suggest that, in the future, laminin 5 gamma 2 chain expression may be used as an indicator of incipient malignant transformation of a benign colorectal adenoma.

Adenoma↗
PubMed2001

Laminin-5 gamma 2 chain expression correlates with unfavorable prognosis in colon carcinomas.

Expression of the gamma 2 chain at the invasive front of different tumors has indicated an important role for laminin-5 in cell migration during tumor invasion and tissue remodeling. As there is considerable need for reliable invasion and prognostic markers we evaluated the correlation of laminin-5 gamma 2 chain expression with clinicopathologic parameters and patient survival in 93 primary colon carcinomas. Epithelial cells of normal mucosa were consistently negative for staining. In contrast, positive cytoplasmic staining was observed in 89 tumors (96%). Twenty-four (26%) cases were scored as sparse, 34 (37%) as moderate, and 31 (33%) as frequent gamma 2 chain expression. There was a significant association of laminin-5 gamma 2 chain expression and local invasiveness of colon carcinomas according to Dukes stage (A-C) (p=0.001) and tumor budding (p<0.001). A statistical significance could also be noted in decreasing tumor differentiation (p<0.001) and correlation to tumor size (p=0.032). No correlation was observed to tumor site. Univariate analysis identified laminin-5 (p=0.010), tumor differentiation (p=0.006) and Dukes grade (p<0.001) as significant variables in predicting prognosis. However, by multivariate analyses, this study could not demonstrate that laminin-5 gamma 2 chain expression is an independent predictive factor for survival. The results indicate that laminin-5 gamma 2 chain expression is up-regulated during the progression of human colon cancer and that it plays a role in the aggressiveness of these tumors. Demonstration of laminin-5 gamma 2 chain positivity also facilitates detection of individual cells or minor cell clusters invading the surrounding stroma. Figures on http://www.esacp.org/acp/2001/22-4/lenander.htm.

Adenocarcinoma↗
PubMed2000

Mutagen exposures and chromosome 3 aberrations in acute myelocytic leukemia.

Thirteen patients with acute myelocytic leukemia (AML) and with clonal aberrations involving chromosome 3 were studied. Three patients had monosomy 3, four had trisomy 3, and six had structural aberrations of chromosome 3. In the majority of cases chromosome 3 aberrations were parts of complex karyotypes, but in two patients, the abnormalities appeared as single aberrations, one as an interstitial deletion del(3)(p13p21) and the other as monosomy 3. All breakpoints of chromosome 3 were found in the fragile site regions 3p14.2, 3q21 and 3q26-27. All patients with monosomy 3 or structural aberrations of chromosome 3 and one of the four patients with trisomy 3 had been exposed to mutagens, such as occupational exposures to organic solvents and/or petroleum products or treatments with irradiation or antineoplastic agents. The association among mutagen exposure, structural chromosome 3 aberrations and fragile sites in AML may indicate that targeting of the mutagens to these sites is of importance for the etiology of the disease. Leukemia (2000) 14, 112-118.

Adolescent↗
PubMed2000

A reproducible grading scale for histological assessment of inflammation in ulcerative colitis.

BACKGROUND: Evaluation of histological activity in ulcerative colitis needs to be reproducible but has rarely been tested. This could be useful both clinically and in clinical trials. AIM: To develop reproducible criteria which are valid in the assessment of acute inflammation (activity) and chronicity, and to evaluate these features in an interobserver variability study. METHODS: A six grade classification system for inflammation was developed which could also be fine tuned within each grade. The grades were: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. Ninety nine haematoxylin-eosin sections from endoscopically inflamed and non-inflamed mucosa from patients with distal ulcerative colitis were assessed in two separate readings by three pathologists independently and without knowledge of the clinical status. Interobserver agreement was compared pairwise using kappa statistics. RESULTS: Initially, kappa values between the observers were 0.20, 0.42, and 0.26, which are too low to be of value. Following development of a semiquantitative pictorial scale for each criterion, kappa values improved to 0.62, 0.70, and 0.59. For activity defined by neutrophils between epithelial cells, kappa values were 0.903, 1.000, and 0.907. Complete agreement was reached in 64% of samples of endoscopically normal and in 66% of endoscopically inflamed tissue. Neutrophils in epithelium correlated with the presence of crypt destruction and ulceration. CONCLUSION: A histological activity system was developed for ulcerative colitis that showed good reproducibility and modest agreement with the endoscopic grading system which it complemented. It has potential value both clinically and in clinical trials.

Biopsy↗
PubMed1999

Increased expression of proliferative Ki-67 nuclear antigen is correlated with dysplastic colorectal epithelium in ulcerative colitis.

Because patients with ulcerative colitis have an increased long-term risk of colorectal cancer, colonoscopic surveillance with multiple biopsies is commonly performed for histopathological detection of dysplasia to select high-risk patients for prophylactic colectomy. Improved differentiation between neoplastic vs. nonneoplastic changes is needed because active inflammation may cause significant misinterpretation of nonneoplastic reactive/regenerative changes in the epithelium. We investigated whether the expression of proliferative antigens is correlated with various degrees of epithelial dysplasia and inflammatory changes in biopsy specimens from patients with long-standing ulcerative colitis. Colorectal biopsy specimens from patients undergoing colonoscopic surveillance were analyzed immunohistochemically using two types of monoclonal antibodies: MIB-1 against Ki-67 and NCL-PCNA against proliferating cell nuclear antigen for structural, active inflammatory, and dysplastic changes. Specimens from patients without inflammatory bowel disease or neoplasia were used as controls; these showed no increased proliferation. However, increased staining with the MIB-1 monoclonal antibody was detected in 9% of the specimens from patients with long-standing ulcerative colitis without active inflammation or dysplasia; this was significantly more common in specimens indefinite for dysplasia, probably positive (24%), and in those with definite dysplasia of low (47%) or high grade (67%; P = 0.008). For increased PCNA staining, there was a non-significant correlation (P = 0.30) with increasing degrees of dysplasia. Increased MIB-1 immunostaining was found in 50% and increased PCNA immunostaining in 75% of the specimens displaying mild inflammation. Both antibodies had a 100% increased staining in specimens with moderate or severe inflammation. Increased proliferation as expressed by MIB-1 is thus better correlated with increasing degree of dysplasia than is PCNA. Neither staining method is able to differentiate neoplastic from inflammatory epithelial changes. However, in the absence of active inflammation, immunostaining for MIB-1 may be a valuable adjunct in the confirmation of dysplastic epithelial changes in long-standing ulcerative colitis, particularly in the indefinite changes category.

Biopsy↗
PubMed1999

Spontaneous and cytokine-induced thrombocytopenia in myelodysplastic syndromes: serum thrombopoietin levels and bone marrow morphology. Scandinavian MDS Group, Sweden and Norway.

Thrombocytopenia is a substantial clinical problem for patients with myelodysplastic syndromes (MDS). Cytokine treatment for granulocytopenia and anaemia may further reduce the platelet counts. We studied serum thrombopoietin levels (S-TPO) in 52 patients with MDS and 96 healthy controls and related the results to clinical and morphological variables. S-TPO was also assessed after treatment with granulocyte-CSF (G-CSF) and erythropoietin (EPO) in 30 of these patients. S-TPO in MDS was not a normally distributed variable; mean value was 394 pg/ml, SD +/-831 and median value 123 (12-5000 pg/ml). The controls showed lower S-TPO levels than the patients (median 78 pg/ml, P = 0.003) whereas no differences between the MDS subgroups were observed (P = 0.86). Patients with ringed sideroblastic anaemia (RARS) showed the highest platelet counts and higher S-TPO levels than the controls (P = 0.005). No association between platelet counts and S-TPO levels was found in the patients (P = 0.67). TPO levels were generally low in patients with refractory anaemia with an excess of blasts (RAEB), but very high levels were found in five patients. Patients with a high transfusion need had higher S-TPO levels, whereas bone marrow blast counts, cellularity or megakaryocytes showed no correlation with S-TPO. Patients with 5q- showed lower TPO levels than the other patients, indicating that thrombopoietin is not a mediator of thrombocytosis in these cases. Treatment with G-CSF + EPO significantly reduced the platelet counts (P = 0.0002), but this change was not related to significant changes in S-TPO levels or morphology. Patients with RARS and thrombocytosis who normalized their platelet counts showed a concomitant reduction in S-TPO. This may suggest that the increased platelet counts observed in RARS may be caused by increased S-TPO levels. In conclusion, our study shows that platelet, megakaryocyte and thrombopoietin regulation is rather complex in myelodysplastic syndromes and that spontaneous or induced thrombocytopenia are not usually mirrored by increased S-TPO levels.

Aged↗
PubMed1999

Gastroesophageal reflux in healthy subjects. Significance of endoscopic findings, histology, age, and sex.

BACKGROUND: Our aim was to evaluate which specific factors are of importance for the gastroesophageal reflux seen in presumably healthy subjects. METHODS: We investigated 57 healthy, asymptomatic volunteers with computer-aided medical history interrogation, endoscopy, biopsy specimens from the distal esophagus, manometry, and 24-h ambulatory pH-monitoring. RESULTS: Eight subjects (14%) claimed intermittent reflux symptoms at the computer interview, but they did not have more acid reflux at pH-monitoring than asymptomatic volunteers. Thirteen subjects (23%) had abnormalities at endoscopy, 3 of whom had an erosion in the distal esophagus, and 12 had hiatus hernia. Subjects with hiatus hernia had increased acid reflux at 24-h pH-monitoring compared with those without hernia. If subjects with hernia were excluded, the degree of acid reflux was similar in all age groups. Men had more acid reflux than women, and these differences persisted if subjects with hernia were excluded. There was no correlation of histologic signs of esophagitis in the distal esophagus, lower esophageal sphincter pressure, smoking habit, or body mass index with reflux of acid to the esophagus. CONCLUSION: Hiatus hernia is a common finding in healthy subjects, and it predisposes to gastroesophageal acid reflux. Histologic abnormalities are poorly related to acid reflux in healthy volunteers. We found increased acid reflux in healthy men compared with women, but larger studies are needed to confirm these findings. Symptom evaluation is not sufficient to exclude significant gastroesophageal reflux in healthy volunteers, and we suggest that the possibility of esophageal abnormalities should be excluded by endoscopy in comparative studies of gastroesophageal reflux disease.

Adult↗
PubMed1998

Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients.

Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic syndromes (MDS) in approximately 20% of patients. Previous studies have suggested that treatment with the combination of granulocyte colony-stimulating factor (G-CSF) and epo may increase this response rate. In the present phase II study, patients with MDS and anemia were randomized to treatment with G-CSF + epo according to one of two alternatives; arm A starting with G-CSF for 4 weeks followed by the combination for 12 weeks, and arm B starting with epo for 8 weeks followed by the combination for 10 weeks. Fifty evaluable patients (10 refractory anemia [RA], 13 refractory anemia with ring sideroblasts [RARS], and 27 refractory anemia with excess blasts [RAEB]) were included in the study, three were evaluable only for epo as monotherapy and 47 for the combined treatment. The overall response rate to G-CSF + epo was 38%, which is identical to that in our previous study. The response rates for patients with RA, RARS, and RAEB were 20%, 46%, and 37%, respectively. Response rates were identical in the two treatment groups indicating that an initial treatment with G-CSF was not neccessary for a response to the combination. Nine patients in arm B showed a response to the combined treatment, but only three of these responded to epo alone. This suggests a synergistic effect in vivo by G-CSF + epo. A long-term follow-up was made on 71 evaluable patients from both the present and the preceding Scandinavian study on G-CSF + epo. Median survival was 26 months, and the overall risk of leukemic transformation during a median follow-up of 43 months was 28%. Twenty patients entered long-term maintenance treatment and showed a median duration of response of 24 months. The international prognostic scoring system (IPSS) was effective to predict survival, leukemic transformation, and to a lesser extent, duration of response, but had no impact on primary response rates.

Aged↗
PubMed1998

Autopsy findings in 27 children with haemophagocytic lymphohistiocytosis.

AIMS: Primary haemophagocytic lymphohistiocytosis (HLH) is a fatal childhood disorder. The diagnosis is difficult to establish, clinically as well as histopathologically, and it is markedly underdiagnosed. Because of these difficulties, we wanted to elucidate the histopathological findings in population-based patient material. METHODS AND RESULTS: The post-mortem findings in 27 children with primary HLH diagnosed in Sweden between 1971 and 1986 was reviewed. Twelve of these patients had an affected sibling and three additional children had parental consanguinity. Some of the children showed generalized disease, whereas in others only one or a few organs were affected. The major histological alteration was an accumulation of primarily lymphocytes, but also of histiocytes, some of which exhibited evidence of haemophagocytosis. The haemophagocytic activity may be difficult to detect if there are pronounced post-mortem changes, particularly in the spleen, and it is therefore preferable to perform the autopsy as soon as possible after death in order to minimize autolysis. Haemophagocytosis was most commonly observed in the spleen (17/24), the lymph nodes (17/23) and the bone marrow (9/23), indicating that a negative bone marrow examination does not rule out this diagnosis. Three additional patients had discrete signs of haemophagocytosis in the bone marrow. In the spleen, the lymph nodes and the bone marrow, lymphocytic depletion, pronounced in some cases, could be observed, even without prior treatment with steroids or cytostatics. In the liver, most of the patients demonstrated an infiltration of lymphocytes into the portal tracts similar to that seen in chronic persistent hepatitis (22/27), a finding which is uncommon in infancy and therefore suggestive of the diagnosis HLH. Other organs involved included the thymus, lungs intestine, pancreas, kidney, heart and striated muscle. CONCLUSIONS: The diagnosis of HLH must be based on clinical, histological and additional laboratory findings. A negative bone marrow examination is common. Previous treatment with steroids and/or cytostatic drugs may attenuate or even eliminate the typical histological findings. Liver findings similar to those in chronic persistent hepatitis are common.

Autopsy↗
PubMed1998

Blocking of MHC class I antigens on leukemic B-cells enhances their conjugate formation with cytotoxic lymphocytes and their susceptibility to lysis.

The role of major histocompatibility complex (MHC) class I antigens and adhesion molecules (AM) in the resistance of leukemic B-cells to cell-mediated cytotoxicity was investigated using cells from eight patients with B-chronic lymphocytic leukemia (B-CLL) and six patients with immunocytoma (IC). Both CLL and IC cells were completely resistant to natural killer (NK) and lymphokine activated killer (LAK) cytotoxicity and no binding to effector cells was observed, irrespectively of AM expression. Blocking of MHC class I antigens with monoclonal antibodies or their temporary elimination from leukemic B-cell surface by acid treatment resulted in a significant (p < 0.005) increase in both conjugate formation and susceptibility to lysis, thus suggesting the relevance of MHC class I expression on leukemic B-cells for the NK/LAK resistance phenomenon.

Cell Communication↗
PubMed1997

Morphological changes and apoptosis in bone marrow from patients with myelodysplastic syndromes treated with granulocyte-CSF and erythropoietin.

A study of bone marrow morphology and apoptosis was undertaken in 51 patients with myelodysplastic syndromes (MDS) treated with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO). In 19 of these patients (37%), a significant improvement in the hemoglobin level was found after treatment. Apoptosis was measured using a nick-end labeling (TUNEL) technique. Patients with MDS had a significantly higher percentage of labelled (apoptotic) cells in the bone marrow compared to healthy individuals (56.3 +/- 3.8% vs. 16.2 +/- 1.4%, p = 0.0001). Patients with RAS showed a lower percentage of apoptotic cells than patients with RA (68.5 +/- 9% vs. 46.5 +/- 4.8%, p < 0.05), while patients with RAEB did not differ significantly from either RA or RAS. In the patients who responded to treatment, the bone marrow samples displayed significant morphological changes. The percentages of erythroid precursors and myeloblasts were reduced after treatment, and patients who had ring sideroblasts before treatment also showed a reduction in the percentage of these cells. Total erythroid index also decreased in responding patients. The percentage of apoptotic cells decreased significantly in responding patients (58.8 +/- 4.8% before treatment vs. 44.5 +/- 5.5% after treatment, mean reduction 18.3%, p = 0.0003), whereas no significant change was found in non-responding patients. Our results suggest that one important mechanism behind the positive effects of treatment with G-CSF and EPO is a reduction in the degree of ineffective hematopoiesis in MDS.

Apoptosis↗
PubMed1997

Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model.

Previous studies have shown that approximately 40% of patients with myelodysplastic syndrome (MDS) and anaemia respond to treatment with human recombinant granulocyte-CSF (G-CSF) plus erythropoietin (epo). The present study was designed to investigate pre-treatment variables for their ability to predict erythroid responses to this treatment. 98 patients with MDS (30 RA, 31 RARS, 32 RAEB, five RAEB-t) were treated with a combination of G-CSF (0.3-3.0 microg/kg/d, s.c.) and epo (60-300 U/kg/d, s.c.) for at least 10 weeks. Minimum criteria for erythroid response was a 100% reduction of red blood cell (RBC) transfusion need or an increase in haemoglobin level of > or = 1.5 g/dl. 35 patients (36%) showed responses to treatment. Medium duration of response was 11-24 months. In multivariate analysis, serum erythropoietin levels and initial RBC-transfusion need retained high statistical significance (P < 0.01). Using pre-treatment serum epo levels as a ternary variable (< 100, 100-500 or > 500 U/l) and RBC transfusion need as a binary variable (< 2 or > or = 2 units per month), the analysis provided a predictive score for erythroid response. This score divided patients into three groups: one group with a high probability of erythroid responses (74%), one intermediate group (23%) and one group with poor responses to treatment (7%). This predictive scoring system could be used in decisions regarding use of these cytokines for treating the anaemia of MDS, both for defining patients who should not be given the treatment and for selecting patients for inclusion in prospective trials.

Aged↗
PubMed1997

Hyperplastic foveolar gastropathies and hyperplastic foveolar gastritis.

Thirteen gastrectomy specimens having diffuse (n = 5), focal (i.e., nodular, n = 6) or combined (n = 2) giant hypertrophic folds at gross examination were reviewed. Of the five specimens with grossly diffuse hypertrophic fundic mucosal folds, two had at histology tortuous foveolar hyperplasia (without intraepithelial lymphocytosis) and prominent glandular cysts; they were classified as Ménétrier's gastropathy. The other three specimens with diffuse foveolar hyperplasia had serrated foveolar infoldings with marked intraepithelial lymphocytosis; they were classified as Ménétrier-like lymphocytic gastritis. Of the six, specimens with multiple mucosal nodules at gross examination, four had focal foveolar hyperplasia with crest depression and no intraepithelial lymphocytosis; they were classified as varioliform gastropathy. The other two specimens with multiple nodules at gross examination had focal foveolar hyperplasia with marked intraepithelial lymphocytosis; they were classified as varioliform gastritis. In the remaining two cases, both diffuse and nodular hypertrophic gastric mucosa were found at gross examination; at histology, both foveolar hyperplasia and intraepithelial lymphocytosis were found. The diffuse or focal distribution of the lesions, the occurrence of intraepithelial lymphocytosis and the architecture of the upper part of the crypts (in diffuse foveolar hyperplasias) were valuable criteria in the differential diagnosis between the various types of foveolar hyperplasia of the stomach.

Aged↗
PubMed1996

Prognostic significance of proliferative and apoptotic fractions in low grade follicle center cell-derived non-Hodgkin's lymphomas.

BACKGROUND: The biologic parameters, DNA ploidy and proliferative activity, have been suggested as prognostic factors in non-Hodgkin's lymphoma (NHL). However, reports on the prognostic importance of these factors in follicle center cell-derived (FCC) centroblastic/centrocytic (CB/CC) NHL patients with long follow-up are scarce. METHODS: Apoptotic fractions were quantified in 60 patients with CB/CC NHL by in situ labeling of DNA strand breaks in nuclei [TdT-mediated dUTP/dATP in situ 3'OH--end labeling (TUNEL)]. The findings were related to S-phase and MIB-1 counts, DNA ploidy, and clinical outcome. RESULTS: In CB/CC NHL, the percentages of proliferating and apoptotic cells were lower than in reactive germinal centers (GC; P < 0.05; mean, 0.188 vs 3.263% and 19.05 vs. 69.4% for TUNEL and MIB-1 positive cells in CB/CC and GC, respectively). Significantly higher percentages of MIB-1 and TUNEL positive cells were observed in patients with complete remission when compared with the partial remission / no response group (P < 0.01). The size of proliferative and apoptotic fractions did not correlate with the overall survival of the patients. However, follicular and diffuse growth pattern, elevated serum lactic dehydrogenase, advanced stage, and age indicated a lower probability of 5- and 10-year survival. CONCLUSIONS: The investigation of proliferative and apoptotic fractions in FCC lymphomas may help to define groups of patients to who would benefit from aggressive, high dose therapy protocols and patients to whom less aggressive strategies can be applied safely.

Adult↗
PubMed1996

Analysis of CD34-positive cells in bone marrow from patients with myelodysplastic syndromes and acute myeloid leukemia and in normal individuals: a comparison between FACS analysis and immunohistochemistry.

In patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), expression of the hematopoietic stem cell marker CD34 has been associated with a poorer prognosis. CD34 is usually analyzed by flow cytometry (FC), but may also be analyzed using immunohistochemistry (IH). The present study was undertaken to compare these 2 methods. Bone marrow from 16 patients with MDS and 12 with AML and from 12 healthy young volunteers was studied. The expression of CD34 was analyzed with FC on fresh bone marrow cells and with IH on sections of paraffin-embedded bone marrow. The correlation between FC and IH was good both for patients with MDS (p<0.0001) and AML (p<0.01). However, in patients with a high number of CD34-positive cells, the FC method seemed to result in a higher percentage of positive cells compared to the IH method. In normal bone marrow, the ratio between the percentage of CD34-positive cells and the percentage of bone marrow blasts was approximately 0.8. In the whole group of MDS patients, this ratio was 1:1, while in patients with refractory anemia (RA) and ring sideroblastic anemia (RAS) it was 1.6. Patients with MDS differed significantly from patients with de novo AML, who showed a ratio of only 0.23 (p<0.01). We conclude that the FC and IH methods for measuring expression of CD34 are well-correlated in MDS and reasonably well correlated in AML. A stem cell phenotype is more commonly expressed on precursor cells from patients with MDS than from patients with AML.

Acute Disease↗