The OX-40 receptor provides a potent co-stimulatory signal capable of inducing encephalitogenicity in myelin-specific CD4+ T cells

The OX-40 receptor, a member of the nerve growth factor/tumor necrosis factor receptor gene family, is expressed preferentially on autoreactive CD4+ T cells isolated from the site of inflammation in rats with clinical signs of experimental autoimmune encephalomyelitis (EAE). To examine whether the OX-40 receptor has biologic relevance to T cell function, we evaluated the ability of a rat OX-40 receptor-specific antibody to co-stimulate a myelin basic protein (MBP)-reactive CD4+ T cell line. The anti-OX-40 antibody provided a potent co-stimulatory signal to CD4+ T cells when added in conjunction with a submitogenic dose of anti-CD3, but the anti-OX-40 antibody alone did not produce a mitogenic response. The magnitude and dose-response of anti-OX-40 co-stimulation was virtually identical to the signal delivered to T cells when cultured with anti-CD28 in conjunction with anti-CD3. MBP-specific T cells stimulated with both anti-CD3 and anti-OX-40 antibodies expressed increased mRNA and protein for IL-2 when compared to anti-CD3 alone. MBP-specific T cells stimulated with both anti-CD3 and anti-OX-40 antibodies were also able to induce EAE when transferred into naive Lewis rats. In contrast, cells stimulated with anti-CD3 alone were not encephalitogenic. These data suggest that the function of the OX-40 receptor on activated T cells is to provide an alternative pathway for T cell co-stimulation that may be similar in potency to the CD28-mediated signal.     

Expression of growth factors and their receptors in the postnatal rat cochlea

RT-PCR was used to assay for growth factors and receptors from seven different protein families in cochlea tissues of the juvenile rat. There was a broad representation of the growth factor families in all the cochlea tissues examined, though the organ of Corti and stria vascularis expressed a greater variety than the spiral ganglion. This broad expression suggests that a variety of known growth factors play significant roles in the development, maintenance, and repair of the inner ear. The results of this survey serve as a basis for the design of future in vitro experiments that will address the ability of growth factors to protect hair cells from damage and to evoke a repair-regeneration response by injured hair cells.     

Positive correlation between Tono-Pen intraocular pressure and central corneal thickness

OBJECTIVE: To examine the relationship between intraocular pressure (IOP) readings taken by the Tono-Pen tonometer (Mentor O&O, Norwell, MA) and central corneal thickness (CCT). DESIGN: Prospective cross-sectional population study. PARTICIPANTS: There were 651 eyes of 332 healthy subjects. MAIN OUTCOME MEASURES: A questionnaire was given to each subject requesting information on gender, age, race, and other factors that can influence IOP. The IOP then was measured using the Tono-Pen followed by measurements of CCT using an ultrasonic pachymeter. RESULTS: The IOP was found to increase by 2.9 mmHg/100 microns CCT in males and 1.2 mmHg/100 microns in females. For males, CCT was found to be statistically significant in predicting IOP (P < 0.001 in the right and left eyes) and diabetes was of borderline significance (P = 0.012 in the right eye, P = 0.089 in the left eye). For females, CCT was of borderline significance (P = 0.064 in the right eye, P = 0.019 in the left eye). In females, a family history of glaucoma (P = 0.021 in the right eye, P = 0.022 in the left eye) and hypertension (P = 0.010 in the right eye, P = < 0.001 in the left eye) were also significant in the prediction of IOP. Race was found to be a significant predictor of CCT (P < 0.001 in both right and left eyes) for both males and females. CONCLUSION: Clinicians should be aware that, as with the Goldmann applanation tonometer, the Tono-Pen has a systematic error in IOP readings caused by its dependence on CCT. Tono-Pen IOP readings are positively correlated to CCT in males and, to a lesser extent, in females as well. The CCT measurements should be considered to ensure proper interpretation of IOP measurements in the diagnosis and management of disorders in which the CCT or IOP readings are outside normal limits.     

The cerebrovascular manifestations of temporomandibular joint pain dysfunction

Overall 37 patients with painful dysfunction of the temporomandibular joint (TMJ), characterized clinically by headaches and dizziness as well (25 persons) were examined. A study was made of REG. The responsiveness of the sinocarotid node (SCN) was recorded. Diverse changes in the REG readings that attested to the development of cerebral angiodystonia were recorded. Abnormal responsiveness of SCN was discovered. Skillful orthopedic correction of the spatial position of the mandible was associated with noticeable changes in the normalizing and optimizing character of numerous REG readings. These data together with optimization of the responsiveness of the SCN point to the role played by the irritative vascular mechanism in the pathogenesis of headaches and dizziness seen in TMJ dysfunction.     

Immunodepressive effect of transcerebral lasers

The aim of the present paper was to study the effect of infrared laser radiation on endocrine regulation of immunogenesis and on endogenic opioid system. For this purpose experiments on rabbits were carried out. The animals underwent transcerebral radiation with subsequent induction of the primary immune response (PIR) to thymus-dependent antigen (sheep red blood cells). The PIR suppression was revealed in all test animals. It was more graphically expressed in rabbits exposed to impulse radiation. Immunodepression was combined with the increase of glucocorticoid activity of adrenal cortex, while no significant changes in thyroid hormones were registered. The 0.08 Joles impulse radiation cause a palpable fall in opioid concentration in blood plasma, the fact, which can be possibly accounted for the rapid exhaustion of opioid synthesis after their stimulation due to laser radiation.     

Genetic analysis and functional characterization of prothrombins Corpus Christi (Arg382-Cys), Dhahran (Arg271-His), and hypoprothrombinemia

The structural abnormalities and functional characteristics of dysfunctional prothrombin variants in two new kindreds have been determined. Prothrombin Corpus Christi (family 1) was purified and found to have markedly reduced fibrinogen clotting activity, yet normal amidolytic and near-normal platelet aggregating activity. A transition (C to T) at nucleotide position 8885, present in the heterozygous form in affected family members, resulted in the substitution of Cys for Arg 382. This substitution results in the loss of a positive charge within the fibrinogen-binding exosite of thrombin, thus accounting for the observed functional defect. A heterozygous C to T transition was also present at position 19994 in other family members with a hypoprothrombinemic phenotype. This mutation results in the replacement of Gln 541 (CAA) by a premature stop codon (TAA). Prothrombin Dhahran (family 2) was found to have markedly reduced fibrinogen clotting activity, but normal amidolytic activity. Affected family members were found to have a G to A transition at nucleotide position 7312 resulting in the substitution of His for Arg 271. This substitution results in the abolition of a factor Xa cleavage site, yielding meizothrombin rather than thrombin, on activation of prothrombin Dhahran by factor Xa. All but one of the above mutations occur at CpG dinucleotides, thus further supporting the observation of a high incidence of CpG transitions in hereditary dysprothrombinemia. The significant bleeding tendencies of individuals homozygous for prothrombin Dhahran (prothrombin clotting activity 5% to 7%) contrast sharply with the absence of significant chronic bleeding in the proband expressing prothrombin Corpus Christi (prothrombin clotting activity 2%). Our findings underscore the capacity of thrombin to contribute to clinical hemostasis by mechanisms other than its fibrinogen clotting activity.