Complex cells increase their phase sensitivity at low contrasts and following adaptation

One of the best-known dichotomies in neuroscience is the division of neurons in the mammalian primary visual cortex into simple and complex cells. Simple cells have receptive fields with separate on and off subregions and give phase-sensitive responses to moving gratings, whereas complex cells have uniform receptive fields and are phase invariant. The phase sensitivity of a cell is calculated as the ratio of the first Fourier coefficient (F1) to the mean time-average (Fo) of the response to moving sinusoidal gratings at 100% contrast. Cells are then classified as simple (F1/Fo >1) or complex (F1/Fo <1). We manipulated cell responses by changing the stimulus contrast or through adaptation. The F(1)/F(0) ratios of cells defined as complex at 100% contrast increased at low contrasts and following adaptation. Conversely, the F1/Fo ratios remained constant for cells defined as simple at 100% contrast. The latter cell type was primarily located in thalamorecipient layers 4 and 6. Many cells initially classified as complex exhibit F1/Fo >1 at low contrasts and after adaptation (particularly in layer 4). The results are consistent with the spike-threshold hypothesis, which suggests that the division of cells into two types arises from the nonlinear interaction of spike threshold with membrane potential responses.     

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.     

Pituitary content of gonadotropins and receptors for gonadotropin-releasing hormone (GnRH) and hypothalamic content of GnRH during the periovulatory period of the ewe

Studies were undertaken to determine if the number of hypophyseal receptors for GnRH changes at the time of the preovulatory surge of LH in ewes. Concentrations of LH, FSH, progesterone, and estradiol in serum and concentrations of LH and FSH in pituitary were measured. The content of GnRH in the hypothalamus was also determined. Estrus was synchronized in 35 cross-bred ewes by injecting prostaglandin F2 alpha (PGF2 alpha) at 0 and 4 h (7.5 mg each, im) on day 14 of a naturally occurring estrous cycle, followed 30 h later by the injection of estradiol (25 micrograms in safflower oil, im). Five ewes were killed at each of the following times relative to the first injection of PGF2 alpha: 0, 24, 32, 44, 50, 56 and 96 h. Blood samples were collected throughout the course of the experiment. Concentrations of progesterone in serum decreased markedly by 8 h after PGF2 alpha and were uniformly undetectable (less than 300 pg/ml) by 34 h. Concentrations of estradiol in serum increased after the injection of estradiol and returned to basal values 10 h later. Surges of LH, which were usually coincident with surges of FSH, occurred between 43 and 53 h. Concentrations of both LH and FSH in the pituitary declined after the LH surge. There were no significant changes in the amount of GnRH contained in the preoptic area, the median eminence, or the hypothalamus. The number of receptors for GnRH increased at 24 and 32 h compared to the 0 h value and remained elevated at 44 and 50 h. After the LH surge (56 h), the number of GnRH receptors declined and at 96 h was not different from the number measured at 0 h. Since an increase in the number of receptors will result in the formation of more receptor-hormone complex and may lead to an augmented response, these data suggest that an increase in the number of hypophyseal receptors for GnRH may contribute to the preovulatory LH surge in ewes.     

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     

Lyme disease and post-treatment Lyme disease syndrome: the neglected disease in our own backyard

Objectives

A survey was developed to assess experience and opinions about Lyme disease and post-treatment Lyme disease syndrome (PTLDS) among faculties in public health. No previous surveys of public health faculties have been found in the literature.

Study design

This is a cross sectional study of public health school faculty members designed to measure knowledge and experience with Lyme disease and PTLDS using an internet survey instrument.

Methods

Participants were recruited using all the publicly available e-mail addresses of faculty members in all the 50 accredited Schools of Public Health in the United States.

Results

A 15% response rate was seen for the survey. 50% of respondents were from Lyme endemic states. Less than 5% of faculty members consider themselves expert in Lyme or PTLDS. Many faculty members had known someone with Lyme disease or PTLDS, but few had been diagnosed themselves. Most believe that PTLDS can be severe and chronic, is not easy to treat, and does not resolve on its own, but were uncertain about its aetiology. Most respondents also felt that the incidence of Lyme disease will increase and that more education is needed.

Conclusions

The need for further understanding and communication presents an opportunity for public health research and education in Lyme disease and the sequelae of PTLDS.