Expression of P-glycoprotein in normal muscle cells and myogenic tumors.

We have analyzed the expression of the multidrug resistance (mdr-1) gene product, P-glycoprotein, by immunohistochemical staining of frozen tissue sections of human normal muscle fibers and 31 tissue specimens of cases of myogenic sarcomas. The objective of this study was to further characterize what appears to be a variety of responses to therapy in like-appearing but distinct tumors. We have used two mouse monoclonal antibodies that recognize two different epitopes of P-glycoprotein. Mouse monoclonal antibody HYB-241 detects an extracellular epitope of P-glycoprotein, whereas C219 detects a carboxy-terminal intracellular epitope and has recently been reported to cross-react with the mdr-3 gene product. Differential epitope expression was observed among normal muscle fibers with the two antibodies used. Smooth-muscle cells were unreactive for the two antibodies, whereas cardiac and a subgroup of skeletal muscle fibers were intensely stained by C219, but not by HYB-241. P-glycoprotein expression was observed in 23% of the 31 myogenic sarcomas analyzed. Our study was conducted mainly using adult myogenic sarcomas (28 out of 31 cases), with a few cases (three out of 31 cases) of childhood sarcomas. Nineteen tumors were leiomyosarcomas, seven cases were embryonal rhabdomyosarcomas, and five cases were rhabdomyosarcomas. We have considered expression of the mdr-1-coded P-glycoprotein when we observed either HYB-241 and C219 staining, or just HYB-241 immunoreactivities. Although P-glycoprotein expression can now be detected in human sarcomas, further studies are needed, mainly comparing tumor samples before, during, and after therapy, to establish the possible significance of the P-glycoprotein expression in clinical drug resistance.     

Intravenous immunoglobulin may lessen all forms of infection in patients receiving allogeneic bone marrow transplantation for acute lymphoblastic leukemia: a pediatric oncology group study

Fifty patients with refractory acute lymphoblastic leukemia underwent allogeneic bone marrow transplantation after conditioning with high-dose cytosine arabinoside and fractionated total body irradiation. Twenty-nine received intravenous immunoglobulin (i.v.Ig) infusion, primarily to prevent cytomegalovirus infection, and 21 did not. The two groups were biologically comparable. Seven (24.5%) of the i.v.Ig-treated and 14 (66.7%) of the non-i.v.Ig-treated patients developed systemic viral, fungal or bacterial infections and/or interstitial pneumonitis (p less than 0.005), which were fatal in three and 12 cases respectively (p less than 0.001). Currently, 23 (79.3%) of the 29 i.v.Ig-treated and eight (38.1%) of the 21 non-i.v.Ig-treated patients are alive and well (p less than 0.01). We conclude that prophylactic i.v.Ig infusions may reduce the frequency of all forms of serious infection in patients with acute lymphoblastic leukemia undergoing allogeneic marrow transplantation, and thereby improve their survival expectation.     

Further characterization of the pigment in pseudomelanosis duodeni in three patients

Pseudomelanosis duodeni is a rare condition in which dark pigment accumulates in macrophages located in the lamina propria of the duodenal mucosa. Three cases are reported here and the literature is reviewed. No clinical association can be found that points clearly to the underlying etiology. Electron probe x-ray microanalysis was used to study the pigment in macrophage granules in 2 of our patients and demonstrated high iron and sulfur content. Iron accumulation in ferritinlike particles was detected in absorptive cell lysosomes. A possible mechanism for the accumulation of absorbed iron by macrophages is considered.     

Pancreatitis associated with bone marrow transplantation in children.

Vomiting, abdominal pain and distension, common findings in children who receive bone marrow transplants (BMT), are usually attributed to chemo-irradiation and mucositis, universally found in these patients. We report seven children, 3.5% of BMT patients at our institutions, with these symptoms who were found to have mild to severe pancreatitis during conditioning for or after receiving BMT. All patients were receiving drugs known to cause pancreatitis, such as adrenocorticosteroids and sulfonamides as well as numerous putative pancreatotoxins such as cyclosporin A and cytosine arabinoside. Five of the seven patients had suffered from graft-versus-host disease. In patients who have received BMT, upper gastrointestinal symptoms should not be attributed to mucositis or chemo-irradiation without first testing for pancreatitis.     

Involvement of programmed cell death in preimplantation embryo demise

Fragmentation is frequently observed in animal and human embryosobtained via in-vitro fertilization (IVF), and is known to beassociated with decreased pregnancy rates and poor survivalfollowing cryopreservation. We postulate that embryo fragmentationis a consequence of activated programmed cell death (PCD) andsubsequent apoptosis and discuss evidence of morphological,histological and biochemical features compatible with the occurrenceof PCD in preimplantation embryos. If PCD is an underlying causeof the high incidence of the fragmentation seen in human pre-embryos,it remains to be determined whether this is reflective of thenatural incidence of lethal chromo somes in the human populationor due to the IVF procedure and culture conditions.     

Mycobacterial infection and atopy in childhood: A systematic review

The epidemiological relation between mycobacterial infection and the prevalence of atopic disease in humans is still unclear. This is in contrast to studies in murine models in which a clear suppression of atopic symptoms was observed after exposure to mycobacteria or mycobacterial products. We therefore wanted to provide a systematic overview of the published literature on the relationship between mycobacterial infection and atopic disease and to evaluate the causal relationship in a meta-analysis. The EMBASE and MEDLINE databases were searched systematically for papers published in the English literature (1966-2005) on the relation between mycobacterial infection and atopic disease. Original observational or interventional studies involving the paediatric population were included. Two authors independently reviewed articles for data on mycobacterial exposure and atopic disease outcome. Any differences were resolved by discussion. Of a total of 1201 hits, 23 studies (19 cross-sectionals, three case-controls and one prospective cohort) met the inclusion criteria. Only a minority of studies (40%) observed an association between mycobacterial infection and the prevalence of atopic disease outcome. In the meta-analysis, only studies containing data on mycobacterial exposure and atopic disease outcome variables were included. Only cross-sectional studies, in which the relation between a positive tuberculin skin test and allergic symptoms was studied, observed statistically significant negative correlation (odds ratio 0.63; 95% confidence interval: 0.51-0.79). The results of this review show that the evidence of the relationship of mycobacterial infection and atopic disease is based on observations of cross-sectional studies. In a meta-analysis, calculations showed a high level of heterogeneity (I(2)) within studies with similar design making it difficult to pool effects. This may partly be explained by differences in the type and definition of mycobacterial infection and lack of uniformity in the definition of atopy. The results show that only a minority of studies in the literature shows any evidence of inverse relationship between mycobacterial exposure and atopic disease outcome. The fact that the present epidemiological evidence on the relationship between mycobacterial infection and the development of atopic disease is based mainly on cross-sectional observational studies indicates the need for population-based prospective studies to address this issue. This issue needs to be addressed in view of recent suggestions to developing mycobacterial-based vaccines against atopic disease in the future.     

Characterization of rearranged Y chromosomes in human testicular tumor cell lines

Cytogenetic analysis of four cell lines established from two different human testicular tumors revealed rearranged or missing Y chromosomes. Southern blot analysis and in situ hybridization with different Y-derived human DNA sequences revealed the existence of Y chromosomal material even in a line without a cytogenetically visible Y chromosome and clarified the composition of Y marker chromosomes.