Parental influence on obesity in Northern Plains American Indian youth

Little is known regarding American Indian (AI) parental influence on children's diet and physical activity (PA), or if this influence is associated with childhood weight. We compared AI parents' diet, PA, and support for these behaviors with the child's body mass index. Scores for parental support of positive PA and diet were higher among parents of overweight/obese children. Parent PA and nutrition behaviors were in a similar, but not significant, direction with respect to child body mass index. Findings suggest that future research is needed to determine what parental, societal, or community variables influence AI children to engage in healthy eating and PA, especially if they are overweight or obese, and the age at which these variables would have the most impact on these behaviors.     

Besonderheiten des Azinuszellkarzinoms des Pankreas

Pancreatic acinar cell carcinoma (ACC) is a rare tumor of the exocrine pancreas. Demonstration of acinar differentiation by immunohistochemistry defines the diagnosis. ACC is an aggressive tumor; however, it has a less dismal prognosis than ductal adenocarcinoma. Molecular alterations that are found in ductal adenocarcinomas, such as KRAS mutations, are absent in ACCs. In contrast, genome-wide and epigenome-wide analyses have described altered DNA methylation patterns, chromosomal amplifications and deletions, and mutational signatures typical for defective DNA repair mechanisms. Up to 14% of ACCs show mismatch repair deficiencies, resulting in the possibility to treat these tumors with recently approved checkpoint inhibitor pembrolizumab.     

Monoclonal antibody BA-1 does not bind to hematopoietic precursor cells

Monoclonal antibody BA-1 binds to B lymphocytes, to cells from most cases of non-T acute lymphoblastic leukemia (ALL), and weakly to neutrophils. To determine whether BA-1 also reacts with hematopoietic progenitor cells (HPC), we studied the effect of removal of BA-1+ cells from human bone marrow on the proliferation in vitro of the trilineage precursor cell CFU-GEMM, and on the committed progenitor cells of granulopoiesis (CFU-C) and erythropoiesis (BFU-E/CFU-E). Complement- mediated cytotoxicity using BA-1 at concentrations far beyond those required to lyse BA-1+ bone marrow cells and ALL cells did not result in inhibition of colony formation in any of the assays. A rosette separation method, using ox red blood cells coated with BA-1, resulted in enrichment of HPC in the BA-1-depleted interface, whereas very few HPC were found in the BA-1-enriched pellet. Both methods indicate that BA-1 does not bind to HPC, although binding of the antibody to the lymphohematopoietic stem cell cannot be excluded yet. The high cytotoxic capacity of the IgM antibody BA-1, and the lack of reactivity with HPC, make the antibody particularly suitable for use in autologous bone marrow transplantation for patients with ALL.     

Biallelic neutrophil Na-antigen system is associated with a polymorphism on the phospho-inositol-linked Fc gamma receptor III (CD16)

Neutrophils express two distinct types of receptor for the Fc region of IgG, FcRII and FcRIII, in amounts of 10,000 to 20,000 FcRII (40 Kd) and 100,000 to 200,000 FcRIII (50 to 80 Kd) per neutrophil. We showed that the FcRIII exhibits genetically determined heterogeneity, detectable by differences in electrophoretic mobility with sodium dodecyl sulfate (SDS) as well as by reaction with antibodies against the biallelic neutrophil-specific antigen system NA. FcRIII was precipitated with an FcRIII-specific monoclonal antibody (MoAb) from the neutrophils of 35 donors. NA1NA1 donors expressed an FcRIII with a molecular weight (mol wt) of 50 to 65 Kd, NA1NA2 donors expressed an FcRIII with a mol wt of 50 to 80 Kd, and NA2NA2 donors expressed an FcRIII with a mol wt of 65 to 80 Kd. Statistical analysis showed that the electrophoretic heterogeneity corresponds with the NA polymorphism (k = 1). Sequential immunoprecipitation with a MoAb against NA1 and a MoAb against anti- FcRIII, followed by SDS-polyacrylamide gel electrophoresis (PAGE), showed that NA1-FcRIII is distinct from NA2-FcRIII. Moreover, immunoprecipitation with a MoAb against NA1 yielded a protein of 50 to 65 Kd, and immunoprecipitation with human anti-NA2 sera or an MoAb against NA2 yielded a protein of 65 to 80 Kd. Preincubation of NA1NA2 neutrophils with F(ab')2 fragments of an MoAb against anti-NA1 reduced binding of IgG dimers to these cells with about 50%, whereas it completely prevented binding of the dimers to NA1NA1 neutrophils. Inhibition experiments with the MoAb against NA2 yielded the same results for NA1NA2 cells, whereas binding of IgG dimers to NA2NA2 cells was completely prevented. Thus, the products of both NA alleles bind IgG. Immunoprecipitation from the medium of neutrophils either stimulated with formyl- methionyl-leucyl-phenylalanine (FMLP) or treated with glycosyl-phosphatidyl-inositol-specific phospholipase C (GPI- PLC) showed that both the NA1-FcRIII and the NA2-FcRIII are released from the cell surface, indicating that both forms of FcRIII have some structural features in common. Deglycosylation of FcRIII from homozygous donors yielded material that showed several bands on SDS- PAGE. GPI-PLC treatment of neutrophils indicated that all of this material is phosphatidyl-inositol linked.     

Expression and structure of CD22 in acute leukemia

The purpose of this study was to examine the expression and structure of CD22 in B cell precursor acute lymphoblastic leukemia (BCP-ALL), acute myeloid leukemia (AML), and T cell acute lymphoblastic leukemia (T-ALL). By using immunofluorescence microscopy and flow cytometry we observed that CD22 is expressed not only in the cytoplasm (as previously reported) but also on the cell surface of virtually all (15/16) BCP-ALL examined. CD22 that was biosynthetically labeled with 35S-cysteine and immunoprecipitated from the uncommon cytoplasmic CD22- positive/surface CD22-negative BCP-ALL cells was analyzed by single- dimension sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Our results indicated that the cytoplasmic form of CD22 comigrated with 125I/lactoperoxidase-labeled surface CD22. Therefore, cytoplasmic CD22 is probably a pool of fully processed glycoprotein. We also observed unusual cases of AML (approximately 20%) that expressed cytoplasmic CD22 based on immunofluorescent staining; however, biosynthetic labeling and immunoprecipitation revealed an apparently cross-reactive protein(s) of approximately 250 to 300 kd in AML cells. No T-ALL cell lines examined expressed either cytoplasmic or surface CD22. Thus, cytoplasmic and surface expression of bona fide CD22 appears restricted to B cells, which suggests that this molecule subserves a function unique to B cells.     

Prolonged CD4 depletion after sequential autologous peripheral blood progenitor cell infusions in children and young adults

Administration of mobilized peripheral blood progenitor cells (PBPCs) after high-dose chemotherapy rapidly restores multilineage hematopoiesis, but the ability of such products to restore lymphocyte populations remains unclear. In this report, we evaluated immune reconstitution in a series of patients treated with sequential cycles of high-dose chemotherapy, followed by autologous PBPC infusions (median CD34(+) cell dose 7.2 x 10(6) cells/kg [range 2-29.3]). Although patients experienced rapid reconstitution of B cells and CD8(+) T cells, we observed CD4 depletion and diminished immune responsiveness in all patients for several months after completion of therapy. Mature CD4(+) T cells contained within the grafts did not appear to contribute substantially to immune reconstitution because CD4 counts did not differ between recipients of unmanipulated T-cell replete infusions versus CD34 selected, T-cell-depleted infusions. Rather, at 12 months after therapy, total CD4 count was inversely proportional to age (rho = -0.78, P =.04), but showed no relationship to CD34 cell dose (rho = -0.42, P =.26), suggesting that age-related changes within the host are largely responsible for the limited immune reconstitution observed. These results demonstrate that in the autologous setting, the infusion of large numbers of PBPCs is not sufficient to restore T-cell immune competence and emphasize that specific approaches to enhance immune reconstitution are necessary if immune-based therapy is to be used to eradicate minimal residual disease after autologous PBPC transplantation. (Blood. 2000;96:754-762)     

Approaching the controversies in antibacterial management of cancer patients

The principles for management of infectious complications in cancer patients are continuing to evolve. The critical element includes the prompt institution of broad-spectrum antibiotic(s) empirically when granulocytopenic patients become febrile and continuation and modification of the regimen in patients with persistent fever and granulocytopenia. The view is presented that antibiotics provide systemic prophylaxis as well as therapy in persistently granulocytopenic patients and that they should be continued until all signs of infection have cleared or the granulocyte count has recovered. Such aggressive therapy, supplemented by continued evaluation and monitoring of the patient, can significantly reduce infection-relation morbidity and mortality.     

A prospective randomized comparison of endoscopic ultrasound- and computed tomography-guided celiac plexus block for managing chronic pancreatitis pain

OBJECTIVE: Computed tomography (CT)-guided celiac plexus neurolysis has been used for controlling the chronic abdominal pain associated with intra-abdominal malignancy and chronic pancreatitis. Endoscopic ultrasound (EUS)-guided celiac plexus neurolysis has been reported to have some success in controlling pain from pancreatic cancer. The aim of this study is to assess the efficacy of EUS-guided celiac plexus block versus CT-guided celiac plexus block for controlling the chronic abdominal pain associated with chronic pancreatitis. METHODS: Patients enrolled were randomly assigned to EUS-guided or CT-guided celiac plexus block. Pain scores were determined pre- and postceliac block for both techniques. Follow-up was obtained by a nurse at 1 day post-block, then weekly thereafter for 24 wk. Patients also rated overall experience with these procedures. The EUS celiac block was performed with a 22-gauge sterile needle inserted into the celiac region with guidance of real-time linear array endosonography followed by injection of 10 ml of bupivacaine (0.75%) and 3 ml (40 mg) of triamcinolone on both sides of the celiac area. RESULTS: Twenty-two consecutive patients (10 men, 12 women), were ultimately enrolled in this study between 7/1/95 and 12/30/95; four patients were excluded for protocol violations. We performed EUS-guided celiac block in 10 patients and CT-guided celiac block in eight. A significant improvement in pain scores with reduction in pain medication usage occurred in 50% (five of 10) of patients having the EUS block. The mean postprocedure follow-up was 15 weeks (range: 8-24 wk). Persistent benefit was experienced by 40% of patients at 8 wk and by 30% at 24 wk. In the patients with CT block, however, only 25% (two of eight) had relief. The mean follow-up was 4 wk (range: 2-6 wk). Only 12% (one of eight) had some relief at 12 wk of follow-up. There were no complications. EUS-guided celiac block was the preferred technique among patients who experienced both techniques. A cost comparison between both celiac block techniques shows EUS to be less costly than CT. CONCLUSIONS: EUS-guided celiac block provided more persistent pain relief than CT-guided block and was the preferred technique among the subjects studied. EUS-guided celiac block appears to be a safe, effective, and less costly method for controlling the abdominal pain that can accompany chronic pancreatitis in some patients.