Secretion,blood levels and cutaneous expression of TL1A in psoriasis patients

TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker.     

Vulvar leiomyomatosis in a patient with esophagogastric leiomyomatosis: review of the syndrome

A case of vulvar leiomyomatosis in a young adult with a history of esophagogastrectomy as a child for esophagogastric leiomyomatosis is presented. The steroid receptor profile of the tumor is described. Therapy with a combination of gonadotropin suppression and surgery was undertaken. The literature pertaining to this rare combination is discussed.     

Free thyroxine and 3,3',5'-triiodothyronine levels in cerebrospinal fluid in patients with endogenous depression

Total and free concentrations of T4 and rT3 in serum and cerebrospinal fluid were estimated by ultrafiltration in 12 patients with unipolar endogenous depression before and after electroconvulsive treatment. Recovery from depression resulted in a decrease in CSF concentrations of free T4 (median) (26.2 to 21.4 pmol/l, p less than 0.02) and free rT3 (14.1 to 12.3 pmol/l, p less than 0.05). Concentrations of free T4 in the cerebrospinal fluid were lower than those in serum (p less than 0.02), the ratio being 0.6. In contrast, levels of free rT3 in the cerebrospinal fluid were considerably higher than those found in serum (p less than 0.01), the ratio being 25. These ratios did not change following recovery from depression. In 9 patients with nonthyroidal somatic illness, concentrations of free T4 and rT3 in the cerebrospinal fluid were similar to those found in patients with endogenous depression, whereas 4 hypothyroid patients and one hyperthyroid patient had considerably lower and higher, respectively, concentrations of both free T4 and rT3. In conclusion, levels of free T4 and free rT3 in the cerebrospinal fluid are increased during depression compared with levels after recovery, probably reflecting an increased supply of T4 from serum and an increased production of rT3 from T4 in the brain. The data also suggest that the transport of iodothyronines between serum and the cerebrospinal fluid is restricted.     

Abdominal zygomycotic thromboangiitis in a patient with AML and t(1;13;14)

 The case report of a 61 year-old man with AML M2 FAB, t(1; 13; 14) and zygomycotic mesenterial thromboangiitis is presented. Two induction cycles of chemotherapy were administered due to primary drug resistance. They were complicated by pneumonia, colonic pseudo-obstruction and perforation with peritonitis. The patient died on the 40th day of therapy, 4 days after undergoing palliative surgery. Zygomycotic thromboangiitis, which very probably contributed to the intestinal perforation, was confirmed morphologically at necropsy. The novel complex chromosomal translocation t(1; 13; 14) (q31; q32; q24) and the problems connected with the diagnosis of invasive fungal infections are discussed. Received: 26 January 1996 / Accepted: 12 June 1996     

Investigations on integration of mossy fiber inputs to Purkyně cells in the anterior lobe

Summary The 275 Purkyn cells identified by the criteria of the previous paper have been investigated with respect to their role as units integrating the input to the anterior lobe from various limb nerves. The discharges from single Purkyn cells have been studied in lightly anesthetized (pentothal) or in decerebrate unanesthetized cats, there being averaging usually of 128 responses in the form of post-stimulus time histograms and cumulative frequency distributions.Single Purkyn cells exhibited a wide variation in their responses to the diverse inputs from the various afferent nerves. Attention was focussed on excitatory and inhibitory responses evoked by mossy fibers with a short latency, usually 10–15 msec for hindlimb afferents. With most Purkyn cells these responses were predominantly evoked from cutaneous nerves, low threshold fibers being particularly effective. A few Purkyn cells were preponderantly excited by afferent volleys from muscle nerves, but there was a large group with a mixed input from cutaneous and muscle nerves. Graded strengths of stimulation of muscle nerves showed that sometimes group I volleys were prepotent, but other Purkyn cells were selectively excited by group II volleys. Though sometimes the afferent volleys from antagonistic muscles had a reciprocal action on a Purkyn cell, as on a motoneurone, it was more common to find similar actions. Also convergence of inputs from forelimb and hindlirnb nerves, both cutaneous and muscular, was not uncommon, particularly in marginal areas between hindlimb and forelimb zones. A special design feature is the convergence onto a Purkyn cell of mossy fiber and climbing fiber inputs evoked by the same afferent volley. This convergence was of particular interest along the parasagittal strip of hindlimb climbing fiber distribution in lobule V.It was not possible to translate the observations into some map of the cerebellar cortex on which are marked the territorial distributions from the various limb afferent nerves. Rather, there was an ill-defined patchy character, closely adjacent Purkyn cells often receiving very different subsets of the total input from the various limb nerves. The unitary integrations accomplished by the individual Purkyn cells are further integrated when their axons converge onto and inhibit the neurones of the cerebellar nuclei, and this integration by convergence would occur in each successive relay on the output pathways from the cerebellum.It is pointed out that the experimental findings on the integrative action of the individual Purkyn cells provide basic information for attempts to construct models simulating cerebellar performance and control.Post-Doctoral Fellow NINDS (1F2NB40, 545101 NSRB).Post-Doctoral Fellow UHF Grant No. FTF-3-UB-70.     

Kinetics of gene expression in murine cutaneous graft-versus-host disease

The kinetics of gene expression associated with the development of cutaneous graft-versus-host disease (GVHD) were examined in a mouse model of MHC-matched allogeneic hematopoietic stem cell transplantation. Ear skin was obtained from recipient mice with or without GVHD between 7 and 40 days after transplantation for histopathological analysis and gene expression profiling. Gene expression patterns were consistent with early infiltration and activation of CD8(+) T and mast cells, followed by CD4(+) T, natural killer, and myeloid cells. The sequential infiltration and activation of effector cells correlated with the histopathological development of cutaneous GVHD and was accompanied by up-regulated expression of many chemokines and their receptors (CXCL-1, -2, -9, and -10; CCL-2, -5, -6, -7, -8, -9, -11, and -19; CCR-1 and CCR-5), adhesion molecules (ICAM-1, CD18, Ly69, PSGL-1, VCAM-1), molecules involved in antigen processing and presentation (TAP1 and TAP2, MHC class I and II, CD80), regulators of apoptosis (granzyme B, caspase 7, Bak1, Bax, and BclII), interferon-inducible genes (STAT1, IRF-1, IIGP, GTPI, IGTP, Ifi202A), stimulators of fibroblast proliferation and matrix synthesis (interleukin-1beta, transforming growth factor-beta1), and markers of keratinocyte proliferation (keratins 5 and 6), and differentiation (small proline-rich proteins 2E and 1B). Many acute-phase proteins were up-regulated early in murine cutaneous GVHD including serum amyloid A2 (SAA2), SAA3, serpins a3g and a3n, secretory leukocyte protease inhibitor, and metallothioneins 1 and 2. The kinetics of gene expression were consistent with the evolution of cutaneous pathology as well as with current models of disease progression during cutaneous GVHD.