Transforming growth factor-beta 1 cooperates with anti-immunoglobulin for the induction of apoptosis in group I (biopsy-like) Burkitt lymphoma cell lines

Group I Burkitt lymphoma (BL) cell lines, which retain the original biopsy phenotype, have been shown to enter apoptosis in response to a number of external stimuli including serum deprivation, thermal shock, addition of calcium ionophore, and ligation of surface immunoglobulin (Ig) by antibody. Transforming growth factor-beta 1 (TGF beta 1) is known to cause growth arrest in BL lines. Here we show that while it is by itself capable of promoting some degree of apoptosis in group IBL cells, TGF beta 1 cooperates with anti-immunoglobulin to this end. Trimeric soluble recombinant human CD40 ligand (sCD40L) was able to inhibit apoptosis induced by the combination of agonists to some degree, but such rescue proved to be short-lived. Both TGF beta 1 and anti-Ig individually caused BL cells to undergo growth arrest at the G1 phase of cell cycle before their entry into apoptosis: the consequence of sCD40L addition was to maintain the cells in cycle for longer. No induction of the apoptosis-protecting gene, bcl-2, occurred in the presence of sCD40L. These findings are discussed, particularly highlighting the relationship existing between survival and the cell cycle. The strong cooperative effects observed between anti-Ig and TGF beta 1 in promoting apoptosis and the inability of CD40 to signal for long-term rescue raise the potential for a novel therapeutic attack on B-cell lymphoma.     

Maximizing Weight Loss After Roux-en-Y Gastric Bypass May Decrease Risk of Incident Organ Cancer

Background

Recent studies have suggested that metabolic surgery reduces cancer risk. This study aims to determine if incident cancer is associated with the extent of weight loss after Roux-en-Y gastric bypass (RYGB).

Methods

Patients at a large tertiary bariatric surgery center were retrospectively reviewed to identify patients with no history of cancer at the time of RYGB. Diagnoses in the electronic health record, a tumor registry, and chart review were used to identify postoperative incident solid organ cancer. The overall incidence of organ cancer was estimated using Kaplan-Meier analysis. The percent total body weight loss (%TWL) in the 48 months after surgery but prior to cancer was compared between those that developed organ cancer versus those that did not using repeated measures linear regression.

Results

The 2943 patients had a mean age of 45.6 years (SD?=?11.1), 81 % were female, and a mean baseline body mass index (BMI) of 47.2 kg/m² (SD?=?7.9). Median follow-up after surgery was 3.8 years (range?=?[<1, 12]). Incident organ cancer developed and was verified in 54 of the 2943 patients (1.8 %). Kaplan-Meier estimates for cancer at 3, 5, and 10 years postsurgery were 1.3, 2.5, and 4.2 %. After adjusting for age, BMI, sex, diabetes, hypertension, and dyslipidemia, patients that developed organ cancer achieved less weight loss (?1.5 % TWL, 95 % CI?=?[?2.9 %, ?0.1 %], p?=?0.034).

Conclusions

Greater weight loss after metabolic surgery may be associated with lower organ cancer risk.

     

A Power Conundrum: Black Women and Their Sexual Partners in the Midwest

The purpose of this research was to determine the extent to which women of African ancestry manifested power in their relationships regarding sexual activities and to examine the influence that specific variables had on their sexual partnerships. A sample (N?=?200) of midlife women aged 40–65, who lived in the Midwest participated in this research. The Sexual Relationship Power Scale was used to examine these relationships. Face-to-face interviews occurred in community settings. Multiple regression equations were used to examine the potential impact of specific variables on sexual functioning. Results of the analysis revealed that variables such as mental quality of life, decision-making, and health promotion were positively associated with sexual relationships. Conversely, depression and life stress scores were negatively linked to sexual relationships. Knowledge gained from this research could be used to explore the phenomena of power as expressed in the daily lives of women of African descent. The research can also be discussed from the perspective of a “Black tax,” that has burdened Black women for centuries and is manifested through years of discrimination, bias, and the lack of equity in most domains of American institutions.     

Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.     

Idiopathic CD4 Lymphocytopenia: Clinical and Immunologic Characteristics and Follow-Up of 40 Patients

Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria.We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19–70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14–24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy.In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm³ (range, 4–294); mean CD8: 236/mm³ (range, 1–1293); mean CD19: 113/mm³ (range, 3–547); and mean NK cell count: 122/mm³ (range, 5–416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count <150/mm³ and NK cell count <100/mm³ were predictors of death.In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency.Abbreviations: AIHA = autoimmune hemolytic anemia, CDC = Centers for Disease Control, CMV = cytomegalovirus, cpm = count per minute, CVID = common variable immunodeficiency, CXCR4 = C-X-C chemokine receptor type 4, HIV = human immunodeficiency virus, HLA = human leukocyte antigen, HPV = human papillomavirus, HTLV-1/2 = human T-cell lymphotropic 1/2, ICL = idiopathic CD4 T lymphocytopenia, IFN-γ = interferon-γ, IL = interleukin, JC virus = John Cunningham virus, LPA = lymphocyte proliferation assay, NK = natural killer, P = patient, PBMC = peripheral blood mononuclear cell, Pwd = pokeweed, SI = stimulation index, sj = signal joint, TREC = T-cell rearrangement excision circle     

Feasibility of Accessing Data in Hospitalized Patients to Support Diagnosis of Malnutrition by the Academy‐A.S.P.E.N. Malnutrition Consensus Recommended Clinical Characteristics

Background: The feasibility of accessing data in hospitalized patients to support a malnutrition diagnosis using the new Academy of Nutrition and Dietetics–American Society for Parenteral and Enteral Nutrition (AND‐A.S.P.E.N.) consensus recommended clinical characteristics of malnutrition is largely unknown. We sought to characterize baseline practice to guide the development of appropriate interventions for implementation of the recommended approach. Materials and Methods: A cross‐sectional survey was conducted of 262 consecutive adults who were referred for dietitian or nutrition support team assessments at 2 tertiary teaching hospitals in Pennsylvania. The availability of data to support the proposed AND‐A.S.P.E.N. approach and the resulting malnutrition diagnoses were examined. Results: Mean ± SD age was 58.2 ± 17.1 years, and half were female. Food intake history was available for 76%, weight history for 67%, and physical examination for loss of fat and muscle mass for 94% and for edema for 84%. Hand‐grip strength was not available. The prevalence of malnutrition among the patients referred for nutrition assessment was 6.7% moderate, 7.6% severe with acute illness; 12.2% moderate, 11% severe with chronic illness; and 0.8% moderate, 0.4% severe with social circumstances. Decline in typical food intake and weight loss were the most commonly used clinical characteristics. Conclusion: Data could generally be accessed to support the AND‐A.S.P.E.N. consensus clinical characteristics for malnutrition diagnosis, but further testing in multiple care settings is needed before these observations may be generalized. Training in assessment methods and dissemination of the necessary tools will be necessary for full implementation.     

Correlations of placental vascular anatomy and clinical outcomes in 69 monochorionic twin pregnancies

Monochorionic monozygotic twins frequently suffer complications from the presence of vascular anastomoses in their monochorionic placentas. Also, sharing of perfusion zones may be unequal, leading to marked growth discordance. This paper analyzes four measures of perinatal outcome (gestational age at delivery, perinatal mortality, birth weight discordance, and presence/absence of hydramnios) according to the vascular patterns of the monochorionic placentas. The worst clinical outcomes were associated with arteriovenous anastomoses in the absence of arterio-arterial and veno-venous anastomoses. The vascular patterns of monochorionic placentas cause significant fetal environmental differences within pairs of monochorionic monozygotic twins. These differences may cause life-long discordance for several phenotypic traits that are not genetically based, and which cause monochorionic monozygotic twins to be “non-identical.” © 1996 Wiley-Liss, Inc.