Altered I-J phenotype in E alpha transgenic mice.

One of the more intriguing puzzles in immunology is the genetic basis for control of murine T-cell I-J determinants. Molecules bearing I-J determinants (I-J molecules) play a role in information trafficking among immunocompetent cells, probably serving as self-recognition molecules that channel regulatory factors to their appropriate target cells. Although it is clear that I-J polymorphism is influenced by the major histocompatibility complex (MHC), molecular genetic studies provide evidence that an MHC gene does not encode I-J molecules. A possible explanation for this paradox is that I-J molecules are a set of non-MHC-encoded T cell receptors that are directly or indirectly selected for by self-MHC products. One key to resolving the genetic and molecular basis for control of I-J determinants is the identification of the MHC gene(s) involved. Herein, data are presented which show that E alpha transgenic mice express an altered I-J phenotype, providing clear evidence that I region class II genes influence I-J polymorphism. Although further study is required to resolve how class II genes mediate this effect, this is a major piece to the I-J puzzle.     

Estimation of normal lumbar flexion with surface inclinometry. A comparison of three methods.

The purpose of this study was to determine the magnitude and clinical significance of surface measurement error in the determination of lumbar spinal flexion. Intrarater, inter-rater and intermethod reliability estimates were obtained using single inclinometry, double inclinometry and back range-of-motion inclinometry methods. Eight healthy subjects were examined independently by two experienced observers and three replicates of each measurement were obtained by each observer in a random sequence. In addition, three replicates of lumbar flexion angles were obtained for each subject by a single observer using the B-200. Reliability estimates were determined by intraclass correlation coefficients and were further compared by paired t tests between observation series. The median range of error was 8.5 degrees using the single inclinometer, 10.5 degrees using the double inclinometer and 16 degrees using the back range-of-motion. The intrarater reliability was generally higher than inter-rater reliability and intermethod reliability was low in most cases reflecting the poor cross-validity across inclinometry methods and between each inclinometry method and the B-200. In conclusion, significant measurement error in estimating lumbar flexion by inclinometry may be expected to occur even in a "controlled" setting using experienced observers, standard examination techniques and asymptomatic healthy subjects. These findings appear to undermine the expectation that the clinician can reliably apply surface inclinometry to estimate loss of spinal mobility for purposes of impairment determination.     

Rotational ablation of balloon angioplasty failures

In this series, we evaluated the use of rotational ablation in stenoses that were previously refractory to balloon angioplasty. Forty-one stenoses were treated; in 26, the balloon did not adequately expand within the lesion and in 15 the balloon could not be delivered to the stenosis. Rotational ablation was technically successful in 40 of 41 (97.6%) of the lesions attempted. Twenty-four patients have been followed (mean time = 9 +/- 5 months) and the restenosis rate was similar to that of balloon angioplasty. Rotational ablation appears well suited and may be the treatment of choice for heavily calcified, severely angulated, and diffusely diseased vessels.     

Achalasia of the Cardia Associated with Hereditary Cerebellar Ataxia

Achalasia of the cardia, a disorder associated with degenerative loss of esophageal myenteric ganglion cells, is reported in association with a recently described progressive neurological disorder, "early onset cerebellar ataxia with retained reflexes." This form of cerebellar ataxia is thought to be inherited as an autosomal recessive disorder. The occurrence of these two very rare neurodegenerative disorders in a single individual is of interest because of the potential genetic and pathogenetic implications of the association.     

Two distinct quisqualate receptors regulate Ca2+ homeostasis in hippocampal neurons in vitro

Addition of quisqualate to mouse hippocampal neurons in vitro elicited two types of changes in [Ca2+]i as assessed by fura-2-based microfluorimetry. The first was a transient spike or group of oscillations and the second was a long lasting "plateau" response. The long-lasting response was abolished on removal of either Ca2+ or Na+ from the external medium or by blocking voltage-sensitive Ca2+ channels. Furthermore, the novel glutamate antagonist 6-nitro-7-cyano-quinoxaline-2,3-dione was a competitive inhibitor of this response. In contrast, none of these manipulations abolished the transient [Ca2+]i spike. Transient [Ca2+]i spikes or oscillations could also be produced by the alpha 1-adrenergic agonist phenylephrine. Production of such an alpha 1-response reduced the size of a subsequently elicited quisqualate response. However production of transient [Ca2+]i spikes with caffeine did not alter the size of the quisqualate-induced spike. We conclude that hippocampal neurons possess two different types of quisqualate receptors. The first mediates quisqualate-induced depolarization and the second mediates Ca2+ mobilization from intracellular stores.     

Experimental Induction of Atheroarteriosclerosis by the Synergy of Allergic injury to Arteries and Lipid-Rich Diet: II. Effect of Repeatedly Injected Foreign Protein in Rabbits Fed a Lipid-Rich, Cholesterol-Poor Diet

Rabbits fed a lipid-rich, cholesterol-poor diet and given concomitant injections of foreign protein, over a period as long as 17 months, developed in their coronary arteries both a) proliferative fibromuscular intimal thickening closely resembling the diffuse intimal thickening that commonly occurs in coronary arteries of man, and b) fatty-proliferative fibromuscular intimal thickening that closely resembles coronary atherosclerosis in man. In contrast, rabbits of another group that were concurrently fed the same diet for as long as 22 months without injections of foreign protein developed changes in arteries of their hearts that resemble neither coronary atherosclerosis nor diffuse intimal thickening in man. Fatty-proliferative changes in aortas of the first group of rabbits are strikingly greater and more closely resemble human aortic atherosclerosis than those in the latter group. In the course of the experiments, the average serum cholesterol was not significantly different in the two groups of rabbits. It was approximately 200 to 250 mg%, which is the average serum cholesterol in adult humans in the United States. These experiments support the hypothesis that the synergy of arterial injury, in particular immunologic injury, and a diet rich in lipid can lead to atherosclerosis in man.     

Visceral target organs in systemic St. Louis encephalitis virus infection of hamsters

Ultrastructural aspects of St. Louis encephalitis virus infection of the major extraneutral organs and tissues of suckling hamsters were examined. In the pancreas, both the exocrine and endocrine portions were equally affected by the virus. A feature apparently unique to flaviviruses was the accumulation of virus particles in all types of secretory granules in this organ. Virus particles were seen within myocardial fibers and within the smooth muscle cells and endothelial cells of small blood vessels of the heart. In the intestines, the lamina propria was the most severely infected, with virus particles accumulated in all cell types.     

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.