Increasing clinical pregnancy rates after IVF/ET. Can immunosuppression help?

OBJECTIVE: To evaluate the safety and efficacy of immunosuppression as an adjunct to improving the success of in vitro fertilization/embryo transfer (IVF-ET). STUDY DESIGN: A randomized, double-blind, placebo-controlled clinical trial. RESULTS: Seventy-five patients were randomized to receive either prednisone (39 patients, 51%) or placebo (36 patients, 49%). Patients in both groups had similar ages and numbers of preembryos transferred. CONCLUSION: Both the implantation and clinical pregnancy rates were higher in the prednisone group (16% vs. 11% and 43.5% vs. 32.3%, respectively). However, these differences did not achieve statistical significance. Evaluation of the ongoing pregnancy rate revealed little difference between the prednisone-treated patients (30.7%) and those receiving placebo (28.0%). There were no side effects reported by patients in either group.     

CD30 expression identifies a functional alloreactive human T-lymphocyte subset

BACKGROUND: CD30 is a member of the tumor necrosis factor/nerve growth factor receptor family and has been proposed as a marker of specific cytokine-producing subsets in humans. Previous studies have examined the expression of CD30 on established T helper type 1 and T helper type 2 cell clones and the function of CD30+ cells after mitogenic stimulation. In this study, we examined the development and function of CD30+ T cells generated in response to alloantigen. METHODS: Primary one-way mixed lymphocyte reactions were established, and the expression of CD30 on T lymphocytes was determined by immunofluorescence and flow cytometry. Fluorescence-activated cell sorting was utilized to define the cytokine profile of alloactivated CD30+ cells after restimulation with anti-CD3 monoclonal antibodies or alloantigen. The effect of cyclosporine on the development of CD30+ cells, and on cytokines produced by CD30+ T lymphocytes, in response to alloantigen was determined. RESULTS: CD30+ T lymphocytes could be detected on day 2 of mixed lymphocyte reactions and continued to increase in number and proportion through day 6. Both CD4 and CD8 T cells expressed CD30 after primary alloantigenic stimulation. CD30+ T cells are a subset of alloactivated T cells and are the major source of interferon-gamma and interleukin-5 produced in response to alloantigen. Cyclosporine partially, but not completely, inhibits the development of CD30+ cells, and has a greater effect on interferon-gamma production than on interleukin-5 production. CONCLUSIONS: CD30+ T lymphocytes may constitute an important immunoregulatory subset in human allograft rejection.     

Depressed electrical atrial activity in hypertrophic and dilated cardiomyopathies. An electrocardiographic, vectorcardiographic and echocardiographic study]

Myelodysplasia and the myeloproliferative disorders are clonal hematopoietic stem cell disorders with heterogeneous clinical presentations and prognoses. This review highlights some of the recent progress that has been made in these disorders. Specifically, a number of studies have enhanced our understanding of the pathogenesis of these disorders, and potentially useful animal models for primary myelofibrosis have been developed. New, clinically useful prognostic scoring systems have been devised for myelodysplasia and for primary myelofibrosis. New chemotherapeutic approaches and nonmyelosuppressive alternative therapies for myelodysplasia have been studied. Data on the use of interferon for polycythemia vera and the potential leukemogenesis of hydroxyurea have recently become available. Finally, continued progress has been made in the use of allogeneic (related and unrelated donor) and autologous stem cell transplantation for myelodysplasia.     

Reversal of fusimotor reflex responses during locomotion in the decerebrate cat

The effect of brief trains of electrical stimulation, at 2, 3 and 20 x threshold (T), of cutaneous afferents in the medial plantar nerve on the discharges of single medial gastrocnemius static and dynamic gamma-efferents has been investigated at rest and during locomotion in a decerebrate cat preparation. The units were classified as dynamic (10 units) or static (10 units) indirectly on the basis of their resting and locomotor discharge characteristics. Responses were assessed by calculating the change in mean gamma-rate during the 100 ms after stimulus onset compared with a control period. At rest, most dynamic neurones were inhibited by stimulation at 2T (9 of 10 units) and above. In contrast, the resting responses of most static neurones were excitatory at 2T (9 of 10 units) and 3T, while 20T produced static gamma-effects that varied in sign. During locomotion the responses of both types of gamma-efferent were phase related. Two patterns were observed with dynamic units. For seven dynamic neurones, at stimulus levels of 2T (7 units) and above, responses during electromyogram (EMG) bursts were inhibitory while those between bursts were not significantly different from zero. However, for three other dynamic units, a phase-related reversal of reflex responses was observed at some stimulus intensities (always 2T, 3 units) comprising inhibition during, and excitation between, EMG bursts. For static neurones, inhibitory (never excitatory) responses occurred during walking at stimulus intensities of 2T (10 units) and above. The locomotor responses of static units were maximum during (3 units) or between (7 units) EMG bursts and were minimum in the opposite phase of EMG activity. A task-related reversal of reflex responses was thus generally apparent (9 of 10 units) to low intensity stimulation (2T) for static gamma-efferents during locomotion (inhibition) compared with rest (excitation). During locomotion there was a significant linear relation between the magnitude of response and the background gamma-rate for static units and those dynamic units that did not exhibit phase-related reflex reversal (total, 17 units). For dynamic gamma-efferents, inhibition at rest and during locomotion occurred at short (spinal) latencies which were not significantly different and are consistent with the involvement of the same interneuronal pathway. We conclude that pathways of opposite sign may dominate the responses of fusimotor neurones to low threshold cutaneous afferents from the plantar surface of the foot depending on behavioural context. Furthermore, the cutaneous reflex responses of both types of gamma-motoneurones during locomotion appear to vary with the source of the afferent input and do not constitute a general excitatory drive. The results are discussed in relation to the role and reflex control of the fusimotor system.     

IgE secretion is attenuated by an inhibitor of proteolytic processing of CD23 (Fc epsilonRII)

CD23, the low-affinity IgE receptor, is up-regulated on interleukin (IL)-4-stimulated B cells and monocytes, with a concomitant increase in the release of soluble fragments of CD23 (sCD23) into the medium by proteolytic processing of the surface-bound intact CD23. The effect of inhibition of the processing of CD23 on IgE production in human and mouse cells and in a mouse model in vivo was evaluated. CD23 processing to sCD23 from RPMI 8866 (a human Epstein-Barr virus-transformed B cell line) cell membranes was inhibited by a broad-spectrum matrix-metalloprotease inhibitor, batimastat, with an IC50 of 0.15 microM. Batimastat also inhibited CD23 processing in whole RPMI 8866 cells as well as in IL-4-stimulated purified human monocytes with similar IC50. Batimastat inhibited IgE production from IL-4/anti-CD40-stimulated human tonsil B cells as well as mouse splenic B cells in a manner consistent with inhibition of CD23 processing. Release of soluble fragments of CD23 in the cell supernatants of tonsil B cells was inhibited over the concentration range of 1-10 microM batimastat and intact cell surface CD23 was increased on mouse splenic B cells in the presence of these concentrations of batimastat. IgE production of IL-4-stimulated human peripheral blood mononuclear cells was also blocked by 1-10 microM batimastat, again with comparable inhibition of sCD23 release over the same concentration range. Finally, in a mouse model of IgE production, batimastat inhibited IgE production in response to ovalbumin challenge as determined by serum IgE levels. Taken together, the data support a role of CD23 in IgE production and point to CD23 processing to sCD23 as a therapeutically relevant control point in the regulation of IgE synthesis.