U2AF homology motifs: protein recognition in the RRM world

Recent structures of the heterodimeric splicing factor U2 snRNP auxiliary factor (U2AF) have revealed two unexpected examples of RNA recognition motif (RRM)-like domains with specialized features for protein recognition. These unusual RRMs, called U2AF homology motifs (UHMs), represent a novel class of protein recognition motifs. Defining a set of rules to distinguish traditional RRMs from UHMs is key to identifying novel UHM family members. Here we review the critical sequence features necessary to mediate protein-UHM interactions, and perform comprehensive database searches to identify new members of the UHM family. The resulting implications for the functional and evolutionary relationships among candidate UHM family members are discussed.     

Bacillary angiomatosis in a German patient with AIDS

Summary A 52-year old male homosexual patient with acquired immunodeficiency syndrome (AIDS) presented in our clinic with multiple nodular papules (more than 100) spread over the whole body which had developed within 3 months. Bacillary angiomatosis was suspected, which is a bacterial infectious disease recognized recently mainly in patients with AIDS. Histological and immunohistochemical examinations of extirpated skin lesions were in agreement with the diagnosis, and the detection of rod-shaped bacteria in the lesions by Warthin-Starry silver stain confirmed it. The patient was treated with 2 × 100 mg doxycycline per day. The fever disappeared, and the cutaneous lesions showed a slight tendency to improve. However, after 5 days of therapy the patient showed increasing weakness, with muscle and bone pain. The patient died 10 days after the doxycyline therapy had been started. The cutaneous lesions in bacillary angiomatosis may resemble Kaposi's sarcoma and may therefore be misdiagnosed. The disease may be fatal, but timely antibiotic treatment is usually effective; therefore the diagnosis of bacillary angiomatosis is important. Although many cases have been reported from the United States, only one case is known from Europe. Our finding of bacillary angiomatosis in a German AIDS patient supports the concept of a worldwide distribution of this bacterial agent.Abbreviations HIV human immunodeficiency virus type 1 - AIDS acquired immunodeficiency syndrome     

Placental site trophoblastic tumor of the mediastinum

Choriocarcinoma has been described as the most frequent subtype of mediastinal germ cell tumors showing trophoblastic differentiation. We report a unique case of a placental site trophoblastic tumor, which developed in the mediastinum of a 14-year-old boy 2 years after the resection of a mature teratoma. The recurrent tumor was composed of a grossly hemorrhagic and necrotic mass. Histologically, diffusely infiltrating large polygonal cells with focal nodular growth and a teratomatous part containing mature intestinal, respiratory, and squamous epithelium with adjacent cutaneous adnexal structures were found. The typical morphologic features included vessel wall infiltration by the neoplastic cells with fibrinoid deposits and geographic necroses within the tumor masses. Characteristic diffuse positivity for melanoma cell adhesion molecule and human leucocyte antigen G was found on immunohistochemical investigation, confirming the diagnosis of placental site trophoblastic tumor. The patient died 1 year later after polychemotherapy. The outcome of this rare tumor is similar to the reported poor clinical outcome in patients with mediastinal choriocarcinomas.     

β1-Adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?

A substantial body of evidence suggests involvement of the human beta1-adrenoceptor (beta1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. Beta1-AR-mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino acid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402-Arg, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different beta1-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.     

Longitudinal Study of Infant Sleep: Results of 14 Subjects Studied at Monthly Intervals

The sleep of 14 normal infants was studied every month throughout the first year. A computer program incorporated an analysis of multiple variables from polygraphic data as recommended by a recently standardized new born scoring manual. Under our recording conditions, quiet sleep increased during the first 3 months but indeterminate sleep did not decline over the year as expected. This finding is incompatible with the notion that indeterminate sleep reflects immaturity or “undifferentiation” in sleep organization.     

Immune suppression and skin cancer development: regulation by NKT cells

Ultraviolet (UV) radiation is carcinogenic and immunosuppressive. UV-induced immune suppression is mediated by antigen-specific T cells, which can transfer suppression to normal recipients. These cells are essential for controlling skin cancer development in the UV-irradiated host and in suppressing other immune responses, such as delayed-type hypersensitivity. Despite their importance in skin cancer development, their exact identity has remained elusive. We show here that natural killer T cells from UV-irradiated donor mice function as suppressor T cells and play a critical role in regulating the growth of UV-induced skin cancers and suppressing adaptive immune responses in vivo.     

Central and peripheral mediation of human force sensation following eccentric or concentric contractions

Fatigue was induced in the triceps brachii of the experimental arm by a regimen of either eccentric or concentric muscle actions. Estimates of force were assessed using a contralateral limb-matching procedure, in which target force levels (25 %, 50 % or 75 % of maximum) were defined by the unfatigued control arm. Maximum isometric force-generating capacity was reduced by 31 % immediately following eccentric contractions, and remained depressed at 24 (25 %) and 48 h (13 %) post-exercise. A less marked reduction (8.3 %) was observed immediately following concentric contractions. Those participants who performed prior eccentric contractions, consistently (at all force levels), and persistently (throughout the recovery period), overestimated the level of force applied by the experimental arm. In other words, they believed that they were generating more force than they actually achieved. When the forces applied by the experimental and the control arm, were each expressed as a proportion of the maximum force that could be attained at that time, the estimates matched extremely closely. This outcome is that which would be expected if the estimates of force were based on a sense of effort. Following eccentric exercise, the amplitude of the EMG activity recorded from the experimental arm was substantially greater than that recorded from the control arm. Cortically evoked potentials recorded from the triceps brachii (and extensor carpi radialis) of the experimental arm were also substantially larger than those elicited prior to exercise. The sense of effort was evidently not based upon a corollary of the central motor command. Rather, the relationship between the sense of effort and the motor command appears to have been altered as a result of the fatiguing eccentric contractions. It is proposed that the sense of effort is associated with activity in neural centres upstream of the motor cortex.     

Fibre type specific expression of Leu19-antigen and N-CAM in skeletal muscle in various stages after experimental denervation

Leu-19 antigen, which seems to be identical with neural cell adhesion molecule (N-CAM), plays a major role in the innervation of muscle cells, and in adult muscle appears after denervation and during regeneration of muscle fibres, where it acts as part of a signalling system increasing the probability of re-innervation. This combined enzyme-histochemical and immunohistochemical study examined whether this signalling process was regulated in a uniform or differential pattern for type 1 and type 2 muscle fibres. The subscapular nerve of 18 rabbits was transsected with subsequent complete denervation of the supraspinatus muscle. Leu19 and N-CAM immunohistochemistry was performed 2 to 64 days after surgery. Whereas in normal muscle there are virtually no Leu-19/N-CAM positive muscle fibres; from day 2 after denervation an increasing proportion of fibres expressed Leu-19/N-CAM, prior to any neurogenic atrophy. In the early stage of denervation Leul9/N-CAM expression was confined to type 1 fibres. After 11 days nearly all fibres were Leul9/N-CAM positive irrespective of their fibre type. Sixty-four days after denervation type 1 fibres became Leu19/N-CAM negative, while atrophic type 2 fibres showed intensive staining. Thus, expression of Leu-19 antigenity is differently regulated in both fibre types.