Heat-shock proteins in autoimmune arthritis: a critical contribution based on the adjuvant arthritis model

Recognition of self protein epitopes, apart from those engaged in idiotypic network interactions and MHC restriction, is probably a physiological event in the normal functioning immune system. Furthermore T and B cells recognizing self antigens can be easily cloned from healthy individuals and sometimes be shown to confer autoimmune disease by passive transfer in the experimental situation. The issue is how potentially autoaggressive cells can become activated and how such activity can be contained safely. Experimentally, autoimmune disease can be evoked by immunization with autoantigens (encephalomyelitis, thyroiditis etc.) or with foreign antigens that feature antigenic relationships with self antigens (adjuvant arthritis). In both situations transfer of disease has been shown with cloned T cells of a single specificity. In addition, specific control of disease using the same cloned T cells has been achieved. Adjuvant arthritis has been illustrative in these respects. By means of specificity analysis of cloned T cells, a 65 kD heat shock protein of mycobacteria was identified as crucial in the disease. Immunization with this antigen has been found to prevent the development of disease, including forms elicited without mycobacterial involvement. Furthermore, vigorous immunological responses to HSP65 were found both in experimental animals and also in humans as a consequence of exposition to various infectious organisms. By their conserved nature HSPs have ample potential for dangerous mimicry. Recent evidence accumulated suggesting that the same HPS65 may be crucial in human chronic arthritis as well. Therefore it is hoped that extrapolation of the experimental findings to the human situation will help the development of specific means, either T cells or antigens, to control spontaneous autoimmune arthritis in man.     

Evaluating Mitochondrial DNA Variation in Autism Spectrum Disorders

Despite the increasing speculation that oxidative stress and abnormal energy metabolism may play a role in Autism Spectrum Disorders (ASD), and the observation that patients with mitochondrial defects have symptoms consistent with ASD, there are no comprehensive published studies examining the role of mitochondrial variation in autism. Therefore, we have sought to comprehensively examine the role of mitochondrial DNA (mtDNA) variation with regard to ASD risk, employing a multi‐phase approach. In phase 1 of our experiment, we examined 132 mtDNA single‐nucleotide polymorphisms (SNPs) genotyped as part of our genome‐wide association studies of ASD. In phase 2 we genotyped the major European mitochondrial haplogroup‐defining variants within an expanded set of autism probands and controls. Finally in phase 3, we resequenced the entire mtDNA in a subset of our Caucasian samples (～400 proband‐father pairs). In each phase we tested whether mitochondrial variation showed evidence of association to ASD. Despite a thorough interrogation of mtDNA variation, we found no evidence to suggest a major role for mtDNA variation in ASD susceptibility. Accordingly, while there may be attractive biological hints suggesting the role of mitochondria in ASD our data indicate that mtDNA variation is not a major contributing factor to the development of ASD.     

An autoradiographic and HRP study of vestibulocollic pathways in the pigeon

This study examines the connections underlying the vestibulocollic system in the adult pigeon by using retrogradely transported horseradish peroxidase (HRP) to identify neck muscle motoneurons in one set of animals, and transneural anterograde transport of tritiated proline-fucose to delineate the descending medial (MVST) and lateral (LVST) vestibulospinal tracts in a second set of animals. Correlations of location and distribution of HRP-labeled motoneurons and autoradiographically labeled fiber tracts and terminal fields were performed between the two sets of experiments. The right biventer cervicis and complexus neck muscles were subdivided into rostral and caudal halves in ten animals and HRP injected into only half of one of the two muscles in each experiment. Following a 16–48-hour survival, the brain was fixed by intracarotid catheterization and perfusion and the HRP in the brain sections reacted with the tetramethylbenzidine (TMB) blue reaction process. Three groups of HRP-labeled motoneurons were identified in the ipilateral ventral horn of the upper cervical spinal cord: a ventromedial and ventrolateral group within lamina VIII innervating the biventer cervicis and the more rostral part of the complexus muscle, and a dorsolateral group of motoneurons within lamina VII innervating the caudal part of the complexus muscle. The dorsolateral motoneurons with their HRP-labeled axons leaving the cord through the dorsal root are homologous to the spinal accessory nucleus of mammals. Labeled motoneurons were also noted in the ipsilateral medulla adjacent to the medial longitudinal fasiculus (ELM) in a location previously identified as the hy-poglossal nucleus. Additional experiments were performed in which HRP was injected directly into the base of the tongue. The resultant HRP-labeled hypoglossal motoneurons were separate and dorsolateral to the collic motoneurons. Descending vestibulospinal projections from one vestibular labyrinth were identified autoradiographicalry (ARG) by transneural anterograde transport of ³H-proline-fucose injected into the left labyrinthine endolytine endolymph in five animals. Heavily labeled MVST fibers were observed crossing the midline of the brain to enter and descend in the contralateral ELM. Labeled MVST fibers were noted to leave the contralateral FLM and surround the previously identified collie motoneurons in the medulla with intense terminal fields suggestive of synaptic contact. Labeled MVST fibers in the contralateral ventral funiculus of the cord were also noted to innervate the HRP-identified ventromedial and ventrolateral cervical motoneurons, but not the dorsolateral motoneurons in lamina VII. Ipsilateral (left) descending MVST and LVST fibers were less heavily labeled at all levels in the medulla and upper cervical cord. Labeled ipsilateral (left) vestibulospinal fibers were also observed to leave the lateralmost aspect of the left ventrolateral funiculus in the upper cervical cord to terminate among left ventrolateral motoneurons. Our findings are compared and contrasted with previous studies of vestibulocollic pathways.     

Report of the Council on Scientific Affairs of the American Medical Association: ultrasound evaluation of the fetus.

Ultrasound evaluation of the fetus has become a vital part of prenatal care not only to detect abnormalities of fetal growth, but to diagnose congenital anomalies, hydatidiform mole and ectopic pregnancy, to assess fetal well-being, and finally to provide ultrasound guidance for invasive procedures. This article will discuss the role of fetal ultrasonography as we head into the 1990s, the changing concepts of indications for ultrasound scanning, the increasing sophistication of the technique, and the types of anomalies detected by this imaging method.     

Intravenous immunoglobulin in HIV infection: evidence for the efficacy of treatment.

Eight children with symptoms of HIV infection were treated for 12-26 months (median 14 months) with infusions of intravenous immunoglobulin (200 mg/kg) every three weeks. Significant improvement was noted in all children in terms of weight gain, number of infectious episodes, and days spent in hospital. This resulted in a 49% saving in cost on treatment compared with costs accrued previously during inpatient admissions. Immunoglobulin concentrations, which were raised at the start of treatment were not altered, and T4 counts continued to decline slowly. HIV core antigen was detected in four children before treatment, but all became core antigen negative after treatment was commenced, this effect being sustained in three. Intravenous immunoglobulin therefore has major clinical benefit, and by reducing viral activity may delay disease progression.     

Gynaecological Complications of Women Treated with Tamoxifen for Breast Cancer

Summary: We present 6 cases illustrating some of the gynaecological complications associated with tamoxifen treatment of women with breast cancer. The first 2 represent cases of myometrial hypertrophy secondary to tamoxifen use, a postmenopausal woman and a premenopausal women with recurrent carcinoma of the breast. The third is a case of probable ovulation induction in a perimenopausal woman with recurrent breast cancer who was commenced on tamoxifen 20 mg daily. The other 3 cases illustrate some of the endometrial effects associated with tamoxifen therapy in women with a history of breast cancer, namely cystic glandular hyperplasia, endometrial polyps and endometrial cancer.     

Airway management by physicians wearing anti-chemical warfare gear: comparison between laryngeal mask airway and endotracheal intubation

BACKGROUND AND OBJECTIVE: To evaluate the ease with which successful insertion of a laryngeal mask airway can be performed in comparison with endotracheal intubation by medical personnel wearing chemical protective equipment. METHODS: Anaesthetists and non-anaesthetists (each n = 20) participated in the prospective comparative trial in an animal laboratory. The time and success rates of laryngeal mask airway vs. endotracheal tube insertions were measured as performed on anaesthetized monkeys. RESULTS: The results showed that the laryngeal mask airway was inserted more rapidly than the endotracheal tube by both groups (3.6 s and 28.6 s, P < 0.0001). Failed intubation occurred in 35% (anaesthetists) vs. 55% (non-anaesthetists) (P = 0.17). CONCLUSIONS: In view of the 100% success rate of insertion even in unfavourable conditions, the possible role of the laryngeal mask airway in the scenario of a toxic mass casualty event should be considered.     

The Eighth International Childhood Acute Lymphoblastic Leukemia Workshop ('Ponte di legno meeting') report: Vienna, Austria, April 27-28, 2005.

The International Acute Lymphoblastic Leukemia Working Group, the so-called 'Ponte di Legno Workshop' has led to substantial progress in international collaboration in leukemia research. On April 27-28, 2005, the 8th Meeting was held in Vienna, Austria, to continue the discussions about special common treatment elements in randomized clinical trials, ethical and clinical aspects of therapy. Furthermore, collaborative projects of clinical relevance with special emphasis on rare genetic subtypes of Childhood ALL were established. The following report summarizes the achievements and aspects of possible future cooperation.