Tropic effects of otic epithelium on cochleo-vestibular ganglion fiber growth in vitro

Sensory nerve fibers of the cochleo-vestibular ganglion (CVG) innervate the otic epithelium in the early chick embryo by directed growth. To see if the target tissue could exert a tropic influence, we co-cultured CVGs from chick embryos (Hamburger-Hamilton stages 16–30) in a 3D collagen matrix with their normal target epithelium or with other epithelial tissues taken from the same or different stages of development. The pattern of neurite outgrowth and the viability of the CVG after five days in vitro were assessed histologically with a silver method. On the basis of the patterns of neurite outgrowth directed toward the epithelium the cultures were classified as having slightly, mostly, exclusively, or no directed outgrowth. Of 49 cultures containing otic epithelium, 33 had mostly or exclusively directed growth patterns. This effect did not depend on any particular stage difference between co-cultures or on their viability in vitro. Cultures of non-sensory otic epithelium (endolymphatic duct) also presented directed growth patterns. Co-cultures with ectoderm from forelimb or visceral arch had little, if any, directed growth. The directed growth could not be explained simply as a result of guidance by non-neuronal cells or of the viability of the explants. The results are consistent with the hypothesis that the otic epithelium provides a tropic factor that attracts growing CVG fibers.     

Long-term anatomic fate of coronary-artery bypass grafts and functional status of patients five years after operation.

To assess long-term results, coronary and graft angiography was performed 53 to 84 months after operation in 22 of 30 consecutive patients who had undergone coronary-artery bypass grafting before 1973, and who had at least one graft patent at an early (three to nine months) postoperative study. Of the 33 grafts, 31 were patent at late study. All patients had severe symptoms before operation. Of 16 who became asymptomatic early after operation, angina pectoris later redeveloped in 11. Progression of disease in ungrafted vessels accounted for symptomatic deterioration in nine of these 11 patients. We conclude that most grafts patent several months after operation remain so for at least 4 1/2 years, and that although most patients improve symptomatically after operation, symptomatic deterioration is common in the succeeding years and is most often due to progression of disease in ungrafted vessels.     

The pattern of neurogenesis in the retina of the rat

Summary The morphological features of the retina of neonatal rats have been analyzed with the rapid Golgi method in an attempt to provide some embryological observations crucial to the study of neuronal specificity in the visual connections. The retinal neurons and photoreceptors form from primitive epithelial cells that assume the characteristics of neuroblasts. Initially they extend from the internal to the external limiting layers. There is no evidence of free cellular migration or of cells resembling the neuroblast of His. While their perikarya are situated deep within the matrix zone, the first signs of differentiation appear at the external and internal limiting membranes, where the receptor inner segments and ganglion cell axons begin to form. Subsequently the perikarya move through the primitive epithelial processes to the prospective outer nuclear or ganglion cell layers. In the receptor cells, this is accompanied by the differentiation of the rods and cones and of the receptor fibers. In the ganglion cells, the perikaryal translocation is followed by the differentiation of the dendrites and the internal plexiform layer. The amacrine and bipolar cells follow a similar sequence of changes. The receptor outer segments form in conjunction with the processes of pigmented epithelial cells; the differentiation of the ganglion cell dendrites occurs in association with the formation of the amacrine and inner bipolar processes. The amacrine and ganglion cells begin to differentiate first, followed closely by the receptor cells and the bipolar cells. Müller's cells and astrocytes differentiate last. Horizontal cells were not studied. There is a gradient of differentiation, such that the axons and dendrites of the ganglion cells near the optic nerve head differentiate earlier than those located more peripherally. The implications of the findings for the analysis of the mechanisms controlling growth, differentiation, and neuronal specificity in the visual system are discussed.Supported by U.S. Public Health Service Research Grant NS 06115 and GRS Grant 5 SOI FR 05381-08 to Harvard University.     

An Evaluation of Finger Pulse Volume as a Psychophysiological Measure of Anxiety

The present experiment explored the utility of finger pulse volume (FPV) as a measure of anxiety. Subjects were exposed to either a threatening or nonthreatening situation, and indices of physiological arousal (pulse rate (PR) and FPV) and self-report of anxiety (Affect Adjective Checklist (AACL)) were collected. Results indicated that FPV was responsive to changes in experimentally induced anxiety and significantly correlated with PR and AACL, although the strength of these relationships was not substantial. Relevance for psychophysiological theory and the clinical observation of anxiety is discussed.     

Association study of a SNAP‐25 microsatellite and attention deficit hyperactivity disorder

Several lines of evidence implicate synaptosomal‐associated protein of 25 kDa (SNAP‐25) in the etiology of attention deficit hyperactivity disorder (ADHD). Most notably, the coloboma mouse mutant, considered to be a good animal model of hyperactivity, has a deletion spanning this gene. Introducing a SNAP‐25 transgene into these animals alleviates hyperlocomotion. We have identified a novel microsatellite repeat in SNAP‐25 located between the 5′UTR and the first coding exon, and tested for association with ADHD. Case‐control analyses suggest there may be a role of this polymorphism in ADHD, with one allele over‐represented in controls and another over‐represented in probands. Within‐family tests of linkage and association confirmed these findings. Further work is needed to ascertain the role of SNAP‐25 in ADHD and assess the functional significance of this polymorphism. © 2002 Wiley‐Liss, Inc.     

The PTPN22 R620W polymorphism associates with RF positive rheumatoid arthritis in a dose-dependent manner but not with HLA-SE status

We have recently described the association between rheumatoid arthritis and a coding single-nucleotide polymorphism in the intracellular protein tyrosine phosphatase, PTPN22. The disease-associated polymorphism, 1858 C/T (rs2476601), encodes an amino-acid change (R620W) in one of four SH3 domain binding sites in the PTPN22 molecule. We have now extended our initial studies to address three questions: (1) Is the association with rheumatoid arthritis limited to rheumatoid factor (RF) positive disease? (2) Does homozygosity for PTPN22 R620W substantially increase disease susceptibility? (3) Is there an interaction between PTPN22 and the rheumatoid arthritis (RA)-associated HLA-DRB1 shared epitope alleles? A total of 1413 Caucasian rheumatoid arthritis patients and 1401 Caucasian controls were genotyped. The results support the view that PTPN22 was strongly and preferentially associated with RF positive disease (OR=1.75, 95% CI 1.46-2.10, P=1.3 x 10(-9)). The PTPN22 risk allele was not significantly associated with RF negative disease (OR=1.19, 95% CI 0.92-1.53, P=0.18), although a very weak association cannot be completely excluded. There was a strong dose effect on disease risk; two copies of the PTPN22 R620W allele more than doubles the risk for RF positive RA (OR=4.57, 95% CI 2.35-8.89). There was no evidence of a genetic association between PTPN22 and HLA susceptibility alleles.     

Mathematical three-dimensional solid modeling of biventricular geometry

The characterization of regional myocardial stress distribution has been limited by the use of idealized mathematical representations of biventricular geometry. State-of-the-art computer-aided design and engineering (CAD/CAE) techniques can be used to create complete, unambiguous mathematical representations (solid models) of complex object geometry that are suitable for a variety of applications, including stress-strain analyses. We have used advanced CAD/CAE software to create a 3-D solid model of the biventricular unit using planar geometric data extracted from anex vivo canine heart. Volumetric analysis revealed global volume errors of 4.7%, −1.3%, −1.6%, and −1.1% for the left ventricular cavity, right ventricular cavity, myocardial wall, and total enclosed volumes, respectively. Model errors for 34 in-plane area and circumference determinations (mean ±SD) were 5.3±6.7% and 3.8±2.7%. Error analysis suggested that model volume errors may be due to operator variability. These results demonstrate that solid modeling of theex vivo biventricular unit yields an accurate mathematical representation of myocardial geometry which is suitable for meshing and subsequent finite element analysis. The use of CAD/CAE solid modeling in the representation of biventricular geometry may thereby facilitate the characterization of regional myocardial stress distribution.     

Nucleic acid vaccines

There are no adequate vaccines against some of the new or reemerged infectious scourges such as HIV and TB. They may require strong and enduring cell-mediated immunity to be elicited. This is quite a task, as the only known basis of protection by current commercial vaccines is antibody. As DNA or RNA vaccines may induce both cell-mediated and humoral immunity, great interest has been shown in them. However, doubt remains whether their efficacy will suffice for their clinical realization. We look at the various tactics to increase the potency of nucleic acid vaccines and divided them broadly under those affecting delivery and those affecting immune induction. For delivery, we have considered ways of improving uptake and the use of bacterial, replicon or viral vectors. For immune induction, we considered aspects of immunostimulatory CpG motifs, coinjection of cytokines or costimulators and alterations of the antigen, its cellular localization and its anatomical localization including the use of ligand-targeting to lymphoid tissue. We also thought that mucosal application of DNA deserved a separate section. In this review, we have taken the liberty to discuss these enhancement methods, whenever possible, in the context of the underlying mechanisms that might argue for or against these strategies.