Surface antigens on malignant Sezary and T-CLL cells correspond to those of mature T cells

Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T- cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sezary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T- chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.     

Prevention of graft-versus-host disease and bone marrow rejection: kinetics of induction of tolerance by UVB modulation of accessory cells and T cells in the bone marrow inoculum

UVB irradiation (700 J/m2) of bone marrow cells (UVB-BMC) before transplantation into lethally gamma-irradiated (10.5 Gy) allogeneic rats prevents graft-versus-host disease (GVHD) and induces a stable complete lymphohematopoietic chimerism. To better understand the underlying mechanism of the development of stable chimerism and induction of tolerance to donor organs in this model, we examined if the addition of T cells or dendritic cells (DC), as antigen presenting cells (APC), would restore the immunogenicity of UVB-BMC in in vitro mixed lymphocyte reaction (MLR) and induce in vivo bone marrow (BM) graft rejection. Whereas gamma-irradiated, unfractionated BMC induce allogeneic T cells to proliferate, UVB irradiation of BMC abolishes the stimulatory capacity of such cells in a primary MLR. Addition of purified T cells, CD4+ T cells, CD8+ T cells or B cells, respectively, failed to restore the capacity of UVB-BMC to stimulate allogeneic T- cell proliferation. In contrast, the addition of only a small number of splenic accessory cells or purified DC, which by themselves were relatively ineffective in stimulating T-cell proliferation, restored the accessory function and the allostimulatory capacity of UVB-BMC. To define the molecular defect induced by UVB irradiation, cytokines were added as costimulatory factors to primary MLRs and the results showed that the addition of interleukin (IL)-2 or IL-6 but not IL-1 or interferon gamma (IFN-gamma) restored the stimulatory capacity of UVB BMC. This finding suggests that UVB may alter the production, and/or utilization of IL-2 and IL-6 either at the membrane or cytoplasmic level. Parallel in vivo studies showed that addition of DC to UVB BM inoculum resulted in failure of BM engraftment, whereas addition of T cells led to development of fatal GVHD, thus suggesting that UVB modulation of accessory cells reduces graft immunogenicity and prevents BMT rejection, while modulation of T cells prevents GVHD. Our data provide evidence that UVB modulation of APC and mature T cells contained within BMC is potentially useful in preventing GVHD without endangering successful engraftment and may serve as a model for induction of adult chimerism and tolerance without the development of GVHD.     

The unmasking of <Emphasis Type="Italic">Pneumocystis jiroveci</Emphasis> pneumonia during reversal of immunosuppression: case reports and literature review

Background  

Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.     

Immunologic heterogeneity of diffuse large cell lymphoma

The cellular lineage of 57 diffuse large-cell lymphomas (DLCLs) was determined using a panel of monoclonal antibodies directed against lineage-restricted and -associated T, B, and monocyte antigens. The majority (82%) were of B cell lineage as determined by the expression of sig and/or B1, with the remaining 16% being of T cell lineage and 2%, of monocyte-myeloid lineage. By the expression of other B cell- restricted and -associated antigens, two major and two minor subgroups could be identified. These subgroups expressed the following phenotypes: (1) B1+B4+sIG+B2- (51%); (2) B1+B4+sIg+B2+ (29%); (3) B1+B4+sIg-B2+ (10%); and (4) B1+B4-sIg+B2- (10)%. The morphology of transformed lymphocytes, the weak to absent expression of the early B cell antigens B2 and sIgD, and the absence of the late B cell differentiation antigens PCA-1 and PC-1 suggested that these tumors were the neoplastic counterparts of normal B cells at the mid-stages of differentiation. Further support for the notion that B-DLCLs correspond to transformed B lymphocytes was concluded from the observation that B cells could be identified in normal spleen that expressed the cell surface phenotype and morphological appearance of the majority of B- DLCLs.     

Protection of adults rechallenged with a human rotavirus

Previous studies of adults challenged with human rotavirus (CJN strain) showed that 74% became infected and 55% of those infected experienced illness. Protection against infection correlated with rotavirus antibody, most significantly (P = .005) serum rotavirus IgG. In this study, 20 previously challenged subjects were reinoculated with the same virus 9-12 months after their initial challenge. Only 1 of 8 subjects not infected after the initial challenge and 2 of 12 infected after the first inoculation became infected after reinoculation; none became ill. Titers of rotavirus antibodies (serum, jejunal, and stool) at the time of reinoculation were about as high as or higher than they were before the initial inoculation. This correlated with greater protection, but the extent of protection was significantly greater (P less than .0001) than predicted based on a previous model relating protection and preinoculation titers of serum rotavirus IgG. Thus, inoculation with human rotavirus provided homotypic protection for at least 9-12 months, and protection remained correlated with higher concentrations of rotavirus antibody. However, the specific relationship between protection and rotavirus antibody was altered after the initial inoculation.     

Nurse Supportive Acts for Mother-Preterm Infant Pairs

Nurse Supportive Acts were measured during the conduct of a nursing intervention designed to facilitate mother-preterm infant acquaintance in the hospital and at home The most frequently performed supportive acts included "active listening" sounding board "information exchange", and "validation" Use of these communication skills allows the health care provider to give care which is fiexible and sensitive for mothers and their preterm infants.     

Efficacy of transrectal ultrasound for identification of clinically undetected prostate cancer.

A total of 51 patients underwent transrectal ultrasound of the prostate before radical cystoprostatectomy for transitional cell carcinoma of the bladder. Each had a normal prostate by digital rectal examination, no history of prostatic adenocarcinoma and no invasion of the prostate by transitional cell carcinoma. Real-time and step-sectioned ultrasound images were interpreted at the time of sonography and results were compared to pathological examination of the step-sectioned prostate specimen. When adenocarcinoma was identified in the specimen, cancer volume was determined. Positive ultrasound scans consisted of those exhibiting hypoechoic lesions. Hypoechogenicity due to transurethral resection defects, benign hyperplasia, vascular structures or shadowing from calcifications was not considered positive. Of 51 patients 27 (52.9%) exhibited no abnormality on ultrasound and were free of cancer in the prostate specimen, while 8 (15.7%) demonstrated a hypoechoic lesion that was proved to be prostate cancer. Seven patients (13.7%) with normal transrectal ultrasound scans had adenocarcinoma of the prostate, while 9 (17.6%) had lesions on ultrasound but no cancer. Based on these results, transrectal ultrasound has a sensitivity of 53.3% and a specificity of 75%. Further analysis reveals that transrectal ultrasound is more accurate in the detection of cancers of greater than 0.20 cc in volume than those of 0.20 cc or less. Transrectal ultrasound also is more accurate in the detection of peripheral zone than transition zone cancers.     

Stimulation of phosphoinositide breakdown in brain synaptoneurosomes by agents that activate sodium influx: antagonism by tetrodotoxin, saxitoxin, and cadmium

Agents that increase intracellular concentrations of Na+ stimulate phosphoinositide breakdown in guinea pig cerebral cortical synaptoneurosomes. When combined, these agents did not have additive effects on phosphoinositide breakdown but did have additive or greater than additive effects with carbamylcholine. Scorpion venom (Leiurus quinquestriatus) and pumiliotoxin B, which induce small increases in influx of 22Na+ in synaptoneurosomes, stimulate phosphoinositide breakdown by about 6- and 3-fold, respectively; both effects are inhibited by tetrodotoxin (TTX). Batrachotoxin (BTX) and veratridine, which cause a large increase in influx of 22Na+ through activation of voltage-dependent sodium channels, induce a 5- to 6-fold dose-dependent increase in phosphoinositide breakdown, which appears competitively inhibited by 5 microM TTX. BTX- and veratridine-elicited influx of 22Na+ into synaptoneurosomes is virtually completely blocked by 5 microM TTX. Agents that block voltage-dependent calcium channels, such as D-600, nifedipine, and Co2+, do not inhibit either influx of 22Na+ or stimulation of phosphoinositide breakdown elicited by scorpion venom, pumiliotoxin B, or BTX. Cadmium ions (200 microM), which are known to block TTX-resistant sodium channels, block phosphoinositide breakdown induced by agents that activate sodium influx through sodium channels. Cadmium blocks BTX-induced phosphoinositide breakdown with an IC50 value of 48 microM, while blocking BTX-induced 22Na+ influx in synaptoneurosomes with a 13-fold lower potency (IC50, 610 microM). In the presence of 0.5 microM TTX, the IC50 for Cd2+ inhibition of BTX-induced 22Na+ influx is now 430 microM. Neither TTX nor Cd2+ antagonize neurotransmitter- or monensin-induced phosphoinositide breakdown. It appears that BTX-induced phosphoinositide breakdown in guinea pig synaptoneurosomes is dependent primarily on activation of TTX-resistant, Cd2+-sensitive sodium channels that account for only a small fraction of the total sodium influx induced by BTX in synaptoneurosomes. However, cadmium also may in some way inhibit phosphoinositide breakdown elicited by sodium channel agents at a point subsequent to sodium influx.     

Seal and whale meat: two newly recognized food allergies.

BACKGROUND: Alaska's marine mammals compose a large portion of the diet of indigenous coastal Alaskan people. Bowhead whales (Balaena mysticetus) and bearded seals (Erignathus barbatus), inhabitants of the Bering and Beaufort seas along Alaska's western and northern coasts, are 2 of the most important subsistence species, serving as major food sources to the native population. OBJECTIVE: To describe an Inupiaq boy with symptoms consistent with an IgE-mediated food allergy after ingestion of bowhead whale and bearded seal meat. METHODS: Extracts of cooked bowhead whale and bearded seal were prepared, lyophilized, and evaluated for protein content. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed for each extract, followed by transfer to nitrocellulose and IgE immunoblots. Skin prick testing was conducted using reconstituted extracts of 1:10 wt/vol dilution. RESULTS: Immunoblots revealed serum specific IgE binding with the extracts of bowhead whale and bearded seal meat. Protein bands of approximately 25, 40, 50, and 90 kDa were found in the seal meat. Protein bands of 55 and 90 kDa were found in the whale meat. Skin prick test results were positive to whale and seal extracts with appropriate positive and negative controls. Ten control subjects had negative reactions to both extracts. CONCLUSION: A patient with moderate anaphylaxis to bowhead whale and bearded seal meat demonstrated serum specific IgE by means of immunoblot and positive skin prick test results. This is the first known reported case of specific IgE to these species.     

The law of maximum expected potential effect: constraints placed on program effectiveness by mediator relationships

The application of mediating variable analysis can yield informationabout the potential effectiveness of interventions that targetsocial behavior. The application of widely accepted statisticalequations to the analysis of simulated data demonstrates thatthe magnitude of the relationship between mediators and behavioraloutcomes directly affects the maximum expected potential effectsize that can be achieved for any given intervention. The useof this relationship in planning and executing interventionsis described. Elements that the field needs to develop beforea truly prospective system of forecasting program effectivenessare outlined.