Differential hypothalamic-pituitary-adrenal activation of the neuroactive steroids pregnenolone sulfate and deoxycorticosterone in healthy controls and alcohol-dependent subjects.

Ethanol and the neuroactive steroids have interactive neuropharmacological effects and chronic ethanol administration blunts the ethanol-induced increase in neuroactive steroid levels in rodent plasma and brain. Few studies have explored neuroactive steroid regulation in alcohol-dependent human subjects. In fact, the regulation of adrenal neuroactive steroids has not been well defined in healthy controls.

Subcutaneous alemtuzumab for Sézary Syndrome in the very elderly.

Sézary Syndrome (SS) is an aggressive T-cell malignancy often presenting in advanced age and associated with poor prognosis. There is no standard therapy and because of co-morbidities, elderly patients are particularly challenging to treat. Alemtuzumab is an anti-CD52 monoclonal antibody that has activity in SS but is profoundly immunosuppressive, leading to great hesitation about its use in older patients.

Bortezomib induces DNA hypomethylation and silenced gene transcription by interfering with Sp1/NF-kappaB-dependent DNA methyltransferase activity in acute myeloid leukemia.

Bortezomib reversibly inhibits 26S proteasomal degradation, interferes with NF-kappaB, and exhibits antitumor activity in human malignancies. Zinc finger protein Sp1 transactivates DNMT1 gene in mice and is functionally regulated through protein abundance, posttranslational modifications (ie, ubiquitination), or interaction with other transcription factors (ie, NF-kappaB). We hypothesize that inhibition of proteasomal degradation and Sp1/NF-kappaB-mediated transactivation may impair aberrant DNA methyltransferase activity.

Post-transplant EBV-negative anaplastic large-cell lymphoma with dual rearrangement: a propos of two cases and review of the literature.

Background: Post-transplant lymphoproliferative disease (PTLD) is a recognized complication of the immunosuppressive regimens associated with solid organ transplantation. The vast majority of these lesions represent monomorphic B-cell lymphoproliferative disease. Rarely, however, T-cell malignancies may emerge, the commonest being anaplastic large-cell lymphoma (ALCL).

Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis.

Deregulation of the Myc pathway and deregulation of the Rb pathway are two of the most common abnormalities in human malignancies. Recent in vitro experiments suggest a complex cross-regulatory relationship between Myc and Rb that is mediated through the control of E2F. To evaluate the functional connection between Myc and E2Fs in vivo, we used a bitransgenic mouse model of Myc-induced T cell lymphomagenesis and analyzed tumor progression in mice deficient for E2f1, E2f2, or E2f3.

Fluctuations in brain concentrations of neurosteroids are not associated to changes in gephyrin levels.

Fluctuations in the brain concentrations of neurosteroids are accompanied by changes in the expression of GABA(A) receptor subunits in the cerebral cortex and hippocampus. Here, we investigated the expression of the postsynaptic molecule gephyrin in the cerebral cortex and hippocampus of pregnant rats, as well as in rats treated chronically with contraceptive drugs. The amounts of gephyrin mRNA and protein did not change during pregnancy and after delivery, as well as in rats treated with ethynylestradiol (EE) and levonorgestrel (LNG) for 4 weeks.

Therapeutic apheresis in hyperleukocytosis and hyperviscosity syndrome.

Therapeutic apheresis (TA), as a way of rapidly eliminating harmful or excessive blood components such as plasma proteins (plasma exchange) or cells (leukapheresis and platelet apheresis), has found broad application in a vast array of hematologic disorders. The most common hematologic indications for TA are leukocytosis in acute leukemias and hyperviscosity syndrome secondary to plasma cell dyscrasia. Leukapheresis is indicated in the initial management of leukostasis in patients with hyperleukocytosis in acute leukemias, particularly myeloid leukemias, or in patients who are at high risk of developing such a complication.

Results of a phase II study of 506U78 in cutaneous T-cell lymphoma and peripheral T-cell lymphoma: CALGB 59901.

Nelarabine (compound 506U78), a novel purine nucleoside, is a soluble pro-drug of 9-beta-D-arabinofuranosylguanine (ara-G). Nelarabine is rapidly demethoxylated in blood by adenosine deaminase to ara-G. Pre-clinical and clinical studies have demonstrated the selective cytotoxicity of ara-G to T-lineage derived cells.

Hypothalamic-pituitary-adrenal axis modulation of GABAergic neuroactive steroids influences ethanol sensitivity and drinking behavior.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis leads to elevations in gamma-aminobutyric acid (GABA)-ergic neuroactive steroids that enhance GABA neurotransmission and restore homeostasis following stress. This regulation of the HPA axis maintains healthy brain function and protects against neuropsychiatric disease. Ethanol sensitivity is influenced by elevations in neuroactive steroids that enhance the GABAergic effects of ethanol, and may prevent excessive drinking in rodents and humans.

A phase 2 study of rituximab in combination with recombinant interleukin-2 for rituximab-refractory indolent non-Hodgkin's lymphoma.

Purpose: The incidence of non-Hodgkin's lymphoma (NHL), the fifth most common malignancy in the United States, has increased over 70% in the last 30 years. Fifty percent to 75% of patients with low-grade or follicular NHL respond to rituximab therapy. However, responses are generally of limited duration, and complete responses are rare.

Fine-needle aspiration biopsy of non-Hodgkin lymphoma for use in expression microarray analysis.

Background: The majority of patients with lymphoma undergo a single biopsy for diagnosis, and there are few opportunities to acquire posttreatment material. Fine-needle aspiration (FNA) biopsy is a minimally invasive procedure, and acquiring routine posttreatment material would require minimal effort and provide needed material for gene expression profiling.

Methods: Ex vivo FNA biopsies were performed using a standard clinical technique with 21-gauge, 22-gauge, 23-gauge, and 25-gauge needles for 8 lymph node specimens and were collected in either RNA stabilization reagent (RNAlater) or Trizol.

T-cell prolymphocytic leukemia: an aggressive T cell malignancy with frequent cutaneous tropism.

Background: T-cell prolymphocytic leukemia (T-PLL), formerly categorized as T-cell chronic lymphocytic leukemia, is a rare and aggressive hematologic malignancy. Although the skin is characteristically involved, it is not a well-recognized entity in the dermatologic literature.

Methods: Six cases of cutaneous T-PLL are presented from a clinical, light microscopic, and phenotypic perspective.

Cutaneous marginal zone B-cell lymphoma in the setting of fluoxetine therapy: a hypothesis regarding pathogenesis based on in vitro suppression of T-cell-proliferative response.

Introduction: Drugs may be an important cause of atypical lymphocytic infiltration. Oftentimes, these infiltrates are in the context of pseudolymphomata. We report a patient who developed lymphocytoma cutis temporally associated with initiation of fluoxetine therapy that later went on to develop cutaneous marginal zone B-cell lymphoma.

Tracheoinnominate artery fistula: combined endovascular and surgical management by emergency stent-graft placement followed by cryopreserved arterial allograft repair.

Tracheoinnominate artery fistula is an uncommon but life-threatening complication usually requiring emergency ligation of the artery. The recent introduction of stent-grafts offers a new therapeutic option for emergency management of hemorrhage. Stent-grafts can be used for definitive treatment or as a bridge to surgery.

Plasma pregnenolone levels in cynomolgus monkeys following pharmacological challenges of the hypothalamic-pituitary-adrenal axis.

Pregnenolone (PREG) is an endogenous neuroactive steroid that is increased in rodent brain and plasma after hypothalamic-pituitary-adrenal (HPA) activation by acute stress or ethanol administration. Plasma levels of PREG metabolites are altered by pharmacological challenges of the HPA axis, however little is known about HPA regulation of PREG levels in monkeys. PREG concentrations were determined by radioimmunoassay in plasma samples from cynomolgus monkeys, following challenge with naloxone (125 and 375 microg/kg), corticotropin-releasing factor (CRF; 1 microg/kg), dexamethasone (130 microg/kg), adrenocorticotropic hormone (ACTH; 10 ng/kg; 4-6 h after 0.

Primary CD20+CD10+CD8+ T-cell lymphoma of the skin with IgH and TCR beta gene rearrangement.

Most cutaneous T-cell lymphomas are derived from mature postthymic T cells of the CD4 subtype. When other less common profiles are encountered, a diagnostic challenge is posed. Accurate categorization is critical because of the specificity of therapeutic regimens, including biologics.

CD8+ lymphomatoid papulosis and its differential diagnosis.

We describe 5 cases (4 males, 14-43 years old; 1 female, 61 years old) of primary cutaneous T-cell lymphoproliferative lesions expressing a CD8/granzyme/CD30-positive phenotype. Four cases were compatible with lymphomatoid papulosis (LyP) based on the clinical course, which was recurrent asymptomatic papular nodular lesions over years responding to methotrexate; granulomatous inflammation and lack of other inflammatory cell elements were characteristic. In 1 case, an initial erroneous diagnosis was made of aggressive epidermotropic CD8+ T-cell lymphoma.

Primary cutaneous CD30+ large cell B-cell lymphoma: a series of 10 cases.

Background: White CD30 expression is described in extracutaneous diffuse large B-cell lymphomas, a primary cutaneous B-cell lymphoma (PCBCL) equivalent is not well defined.

Methods: Between June 1999 and July 2002 the authors encountered 10 patients with CD30+ PCBCLs of the large cell type.

Results: The patients comprised seven women and three men; five patients were over 80 years of age, all except one presenting with solitary plaques.

Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients.

The aim of this work was to study the association between plasma thiol levels and percentage carotid narrowing in a group of 68 patients who underwent a carotid endarterectomy, pertained as a risk factor for vascular and cardiovascular disease. Total plasma thiols were measured by capillary electrophoresis laser-induced fluorescence. The mean values of the hematological parameters studied were within normal limits and 25% of the patients were hyperhomocysteinemic (homocysteine >15 micromol/L).

The absence of CD20 messenger RNA in recurrent cutaneous B-cell lymphoma following rituximab therapy.

Background: Rituximab has been used to treat relapsed low-grade or advanced non-Hodgkin's lymphoma since 1997, targeting the CD20 antigen expressed by B cells. Single-agent rituximab therapy is safe and well tolerated. Recurrences showing a loss of CD20 expression following rituximab therapy have been reported.