Multiple Autoantigen Mimotopes of Infectious Agents Induce Autoimmune Arthritis and Uveitis in Lewis Rats

We found multimolecular antigenic mimicry of arthritogenic autoantigens and peptides from several other “self” or foreign antigens sharing amino acid sequence homologies. Many of these new mimotopes induced arthritis and/or uveitis upon immunization in Lewis rats, indicating a role for multiple antigens in the initiation of a certain autoimmune disease.     

Relationship between transmitter release and presynaptic calcium influx when calcium enters through discrete channels.

We have used a three-dimensional diffusion model of calcium entering the presynaptic nerve terminal through discrete channels to simulate experiments relating transmitter release to presynaptic calcium current. The relationship will be less than linear, or will curve downward, if calcium channels are well separated. It will resemble a power-law function with exponent less than the cooperativity of calcium action if channels are clustered closer together. Large presynaptic depolarizations elicit more release than small depolarizations admitting the same calcium influx. This occurs because large pulses open more channels near each other, with the result that the calcium concentration near release sites is greater, due to overlap of calcium diffusing from adjacent channels.     

Scanning electron microscopic study of degeneration and regeneration in the olfactory epithelium after axotomy

Summary The olfactory epithelium of the adult hamster (Mesocricetus auratus) was examined with the scanning electron microscope following olfactory nerve axotomy. Axotomy results in retrograde degeneration of mature olfactory neurons. Maximum degeneration was observed around day 4. During the degeneration period the epithelium consists primarily of supporting and basal cells. Microvillar columnar supporting cells were observed to have fine cellular processes extending from their lateral border to neighbouring cells. Supporting cells extended to the basal lamina where they terminated in foot-like processes of variable shapes (club, splay and hook). Basal cells which gave rise to new replacement olfactory neurons were observed near the basal lamina. They had a rough cellular surface covered with small granules and fine cellular extensions. Bowman's gland duct cells extended unbranched through the epithelium where they formed funnel duct openings covered with microvilli. During early recovery periods (5–30 days) the number of olfactory neurons in the lower epithelium region increased. We observed olfactory neurons with developing axon and dendritic processes. Specialized growth cone structures were seen at the tips. Olfactory neuron growth cones were elongated or club-shaped and had a ruffled membrane surface. Several thin filopodia extended from the growth cone and made contact with adjacent cells. At late recovery periods (35–120 days) there was a marked increase in the number of olfactory neurons within the middle and lower epithelium regions. Numerous dendritic processes extended to the epithelial surface and terminated in knob-like ciliated structures. Olfactory axons passed basally, forming small intra-epithelial bundles that penetrated the basal lamina then fasciculated into larger bundles within the lamina propria.This study provides detailed three-dimensional observations of the olfactory epithelium following neuron injury, and describes neural degenerative changes, replacement of olfactory neurons, development and maturation. In addition, we describe the structure and basal attachment of supporting cells and their glial-like relation with olfactory neurons.     

Chromosomal Rearrangements in Three Infertile Men

Summary:  Three chromosomal rearrangements: a balanced reciprocal translocation, t(14;10) (q22;q13), a Y-autosome translocation, t(Y;16) (q11;p13) and a deleted Y chromosome, Yq- were detected among 100 infertile men. The autosomal translocation, associated with oligozoospermia was found to be familial with various effects on the female carriers and the proband's father. The patients with the chromosome Y abberations were found to be azoospermic and might have lost the genes necessary for normal sperma-togenesis.
Zusammenfassung:  Unter 100 infertilen Männern wurden drei Chromosomenneuan-ordnungen entdeckt: eine balancierte reziproke Translokation, t(14;10) (q22;q13), eine Y-autosome Translokation, t(Y;16) (q11;p13) und eine Deletion des Y-Chromosoms, Yq-. Die autosomale Translokation bei Oligozoospermie zeigte sich familiär mit verschiedenen Auswirkungen bei den weiblichen Überträgern und dem Vater des Probanden. Die Patien-ten mit chromosomalen Y-Aberrational wiesen eine Azoospermie auf und scheinen die zur normalen Spermatogenese notwendigen Gene verloren zu haben.     

Unlike hypoxia, hypoglycemia does not preferentially destroy GABAergic neurons in developing rat neocortex explants in culture

We tested whether hypoglycemia, like hypoxia, would preferentially destroy GABAergic nerve cells in the neocortex. To this end, rat neocortex explants dissected from 6-day-old rat pups and cultured up to a developmental stage approximately comparable to that of the newborn human neocortex, were exposed to hypoglycemia for different periods. Quantitative light microscopic and immunocytochemical evaluation of the cultures demonstrated that hypoglycemia does not preferentially destroy GABAergic but rather non-GABAergic neurons, a finding quite opposite to what was found after hypoxia. Recent biochemical data from other laboratories which seem to support this difference in neuronal vulnerability are discussed. It is concluded that perinatal hypoglycemia may not form such a serious threat with respect to the genesis of epilepsy as does hypoxia.     

T cells specific for alpha-beta interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing.

Processing of a protein antigen into fragments is believed to be a prerequisite for its presentation by the antigen-presenting cell to the T cell. This model would predict that, in oligomeric proteins, T cells prepared with specificity for regions that are buried within subunit association surfaces should recognize the respective regions in vitro equally well on the isolated subunit or on the oligomer. Three hemoglobin (Hb) alpha-chain synthetic peptides, corresponding to areas that are situated either completely [alpha-(31-45)] or partially [alpha-(41-45) and alpha-(81-95)] within the interface between the alpha and beta subunits of Hb, and a fourth peptide representing a completely exposed area in tetrameric Hb were used as immunogens in SJL/J (H-2s) mice. Peptide-primed T cells were passaged in vitro with the respective peptide to obtain peptide-specific T-lymphocyte lines. T-cell clones were isolated from these lines by limiting dilution. T-cell lines and clones that were specific for buried regions in the subunit association surfaces recognized the free peptide and the isolated subunit but not the Hb tetramer. On the other hand, T cells with specificity against regions that are not involved in subunit interaction and are completely exposed in the tetramer recognized the peptide, the isolated subunit, and the oligomeric protein equally well. The responses of the T-cell lines and clones were major histocompatibility complex-restricted. Since the same x-irradiated antigen-presenting cells were employed, the results could not be attributed to differences or defects in Hb processing. The findings indicate that in vitro the native (unprocessed and undissociated) oligomeric protein was the trigger of major histocompatibility complex-restricted T-cell responses.     

The virD operon of Agrobacterium tumefaciens Ti plasmid encodes a DNA-relaxing enzyme.

The virD locus of Agrobacterium tumefaciens Ti plasmid encodes functions necessary for endonucleolytic cleavage of transferred DNA (T-DNA) prior to its transfer to plant cells. For the overproduction of the VIRD proteins in Escherichia coli a tac-virD operon fusion was constructed. A significant increase in the accumulation of VIRD proteins was observed in a lon protease-deficient E. coli host. The presence of an overlapping open reading frame (ORF) upstream of the VIRD1 coding sequence had a negative effect on VIRD1 production. A preparation containing VIRD proteins catalyzes the conversion of supercoiled (form I) DNA to relaxed (form IV) DNA. This activity is similar to that of a DNA topoisomerase. The relaxation activity lacks DNA sequence specificity, requires magnesium ion, and has no requirement for an energy source. Studies with plasmids that had lost defined DNA segments encompassing various virD coding regions showed that VIRD1 is the DNA-relaxing enzyme. In a density gradient centrifugation experiment, the DNA-relaxing activity sedimented as a 21-kDa polypeptide. Earlier studies of Jayaswal et al. [Jayaswal, R., Veluthambi, K., Gelvin, S. & Slightom, J. (1987) (J. Bacteriol. 169, 5035-5045] have shown that in E. coli VIRD2 alone is not sufficient for endonucleolytic cleavage of T-DNA and requires VIRD1 for its activity.     

Synovial fluid phospholipase A2s and inflammation.

The activation of phospholipase A2 is believed to have an important role in the inflammatory process owing to its induction of eicosanoids, platelet activating factor, and other mediators. Soluble phospholipase A2 has been associated with exudates in different inflammatory conditions. In this review the general physiology and control of this enzyme and, in particular, the most recent findings on human synovial fluid phospholipase A2s are discussed.     

Safety and reliability of external fixation for basicervical and intertrochanteric fractures in high-risk elderly patients

Forty elderly patients with basicervical and pertrochanteric fractures were managed with uniplanar AO external fixator under regional anaesthetic block of the femoral nerve and lateral cutaneous nerve of the thigh from April 2003 to March 2006. The mean age of the patients was 67.9 ± 5.5 years. External fixator application was performed under radiological control after closed reduction had been obtained. Comorbid factors, duration of surgery, duration of hospitalisation, complications, walking ability, time to union and mortality rate were recorded. Patients were followed up for a mean period of 12 ± 4.5 months. Superficial pin tract infection occurred in 13 patients, healing in varus >10° and with shortening >2 cm occurred in six patients, and one patient suffered a spontaneous ipsilateral femoral neck fracture after removal of the fixator. The mean time for union was 10.4 ± 1.2 weeks. Rapid union rate and minor complications obtained in the present study are comparable to those obtained with standard internal fixation techniques. Minimal intraoperative blood loss, short operative time and early patient mobilisation are advantages signifying uniplanar external fixator application under regional anaesthetic block to be a viable option in treatment of basicervical and pertrochanteric fractures in high-risk elderly patients.     

Genetic analysis of host responses in sepsis

During much of the past century, the microbe itself stood at the heart of microbial pathogenesis. Little thought was devoted to the host per se, though it was granted that differences in susceptibility to certain infections did exist between individuals, and between different ethnic groups. During the past 20 years, extraordinary strides in our grasp of mammalian genetics have made the host side of the equation far more approachable. A restricted collection of genes now presents itself as the likely repository for genetic differences that foretell susceptibility to infectious disease. The Toll-like receptors, of which 10 are presently known to exist in humans, offer an excellent example of this genetic reductionism, in that they embody the afferent component of the innate immune system, and strongly influence the containment of an infection from its earliest stages. The Toll-like receptors were identified as the culmination of a long and relentless inquiry into the yet-unsolved clinical problem of sepsis.