The morphology of spinocervical tract neurones in the cat.

1. The morphology of physiologically identified spinocervical tract (SCT) neurones was studied using the intracellular injection of Procion dyes in anesthetized and decerebrate cats. 2. Extracellular recordings were made from SCT neurones at depths between 1000 and 2850 mum from the cord surface but neurones were only stained at depths between 1100 and 2400 mum. 3. The dendritic trees of stained SCT neurones were reconstructed in the transverse plane of the spinal cord. All SCT neurones had well developed dorsal dendrites but despite this it is not possible to consider the twenty-two SCT cells in out sample as consituting a morphologically homogenous population. 4. There was no correlation between the form of the dendritic trees and the depth of SCT neurones in the dorsal horn as determined both from measurements from the dorsal grey-white border and the position of cells with respect to the border between Rexed's laminae II and III. 5. Six types of SCT neurones were identified on the basis of the form of their dendritic trees as viewed in the transverse plane: (1) radially symmetrical, (2) semicircular, (3) large elliptical, (4) bilobed, (5) triangular, (6) small elliptical. Each of these types was found only in a certain region across the dorsal horn although any one region could contain more than one type. 6. Spinocervical tract neurones with small elliptical dendritic trees always had receptive fields encompassing part of the hip or thigh and were unique in being located in the lateral portions of the horn. 7. There was no correlation between the morphology of SCT neurones and their excitatory cutaneous inputs, receptive field size, axonal conduction velocity or depth in the dorsal horn.     

Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells

Immunological memory depends on the long-term maintenance of memory T cells. Although the factors that maintain CD8 T cell memory are well understood, those responsible for CD4 memory are not well defined. We have shown here that interleukin 7 (IL-7) was an important survival factor for CD4 memory T cells that together with T cell receptor (TCR) signals regulated homeostasis of the CD4 memory population in lymphopenic conditions and in the intact immune system. Thus, IL-7 contributes to the maintenance of all naive and memory T cell subsets, and therefore controls the overall size of the T cell pool.     

Factors affecting transfer of experimental autoimmune thyroiditis in rats

Actively induced experimental autoimmune thyroiditis in inbred Lewis rats was comparable using standard Freund's complete adjuvant (FCA) and Perrin's modification of FCA. However, adoptively transferred disease using lymph node cells from rats immunized with Perrin's FCA was significantly more severe. With this adjuvant, and pertussis vaccine as co-adjuvant, transfer was uniformly successful when at least 480 × 10⁶ lymph node cells were taken 10 days after immunization and recipients were killed 3 days after transfer. Lymphocytic infiltrates were seen in recipient thyroids as early as 18 hours after transfer. Whole body irradiation of the recipients at 550 r reduced the severity of transferred disease. The frequency and severity of lesions were higher when the lymph node cells were first incubated with low doses of antigen. Thymectomy of the recipients decreased the severity of transferred disease. Under the conditions tested, transfer of disease could not be accomplished by antiserum alone, even using thyroidectomized donors. Administration of an early immune serum with sensitized lymph node cells significantly depressed the severity of transferred disease, while a late antiserum increased it.     

Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits eosinophil migration

Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1-mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.     

Migration of lymphoblasts to the small intestine. III. Strain differences and relationship to distribution and duration of Trichinella spiralis infection.

In NIH strain mice, in which the majority of Trichinella spiralis are located in the anterior half of the small intestine early in the enteral phase of infection, enhanced localization of mesenteric lymphoblasts, nylon wool separated mesenteric T-lymphoblasts and even oxazolone sensitized peripheral lymphoblasts is most prominent in the anterior region of the small intestine. As the worms move to the posterior half of the small intestine, enahnced localization of lymphoblasts is observed in that region only. In BALB/c mice, in which most of the worms are located in the posterior half of the small intestine, enhanced localization of lymphoblasts is primarily in that region. Expulsion of the worms commences within 2--3 days of a large increase in the number of lymphoblasts localizing in the anterior region of the small intestine in NIH strain mice and likewise follows a second and larger increase in the number of lymphoblasts localizing in the posterior region of the small intestine of BALB/c mice.     

Modulation of Bcl-2 family proteins in primary endothelial cells during apoptosis

We studied the expression of Bcl-2 family proteins during cytokine- and verotoxin (VT)-induced apoptosis in primary human umbilical vein endothelial cells (HUVECs). Our experiments demonstrated that high initial expression of Bcl-2 protein was significantly downregulated in HUVECs treated with IFN-gamma whereas TNF-alpha gave a less pronounced decrease in Bcl-2 level. Treatment with the combination of cytokines was more efficient in downregulating Bcl-2 protein. HUVECs pretreated with cytokines and incubated with VT gave a further significant decrease in Bcl-2 level. Simultaneous measurement of Bcl-xl level did not reveal any significant changes. Bax protein was upregulated in HUVECs stimulated with TNF-alpha alone or in combination with IFN-gamma. However, addition of VT did not give any further increase in Bax level suggesting that Bax upregulation is more important for cytokine- rather than VT-mediated apoptosis. Total endothelial cell growth factor deprivation gave a significant increase in apoptosis accompanied by a decrease of Bcl-2 in apoptotic cells while Bcl-xl and Bax levels were unaffected. Our data indicate that anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax are reciprocally regulated during apoptosis, whilst Bcl-xl is essentially unaffected. This implies that Bcl-2/Bax ratio rather than Bcl-xl controls apoptosis in primary endothelial cells.     

A locus for autosomal dominant anterior polar cataract on chromosome 17p

Inherited cataract is a clinically and genetically heterogeneous disease. Here we report the identification of a new locus for an autosomal dominant anterior polar cataract on the short arm of chromosome 17. To map this new locus we performed genetic linkage analysis with microsatellite markers in a four-generation pedigree. After exclusion of seven candidate loci for cataract, we obtained significant positive LOD scores for markers D17S849 (Z = 4.01 / theta = 0.05) and D17S796 (Z = 4.17 / theta = 0.05). Multipoint analysis gave a maximum LOD score of 5.2 (theta max = 0.06) between these two markers. From haplotype analysis, the cataract locus lies in the 13 cM interval between markers D17S849 and D17S796. This study provides the first genetic mapping of an autosomal dominant anterior polar cataract.      

The influence of the herpes simplex virus-1 DNA template environment on the regulation of gene expression

To determine the role of the HSV-1 genome structure and environment on the regulation of gene expression, we constructed recombinant viruses containing a heterologous gene inserted into either the immediate early ICP0 or late glycoprotein C (gC) genes of HSV-1. The heterologous gene consisted of the SV40 early promoter (without enhancer sequences) linked to the coding sequences for the bacterial chloramphenicol acetyl transferase (CAT). The expression of CAT was examined in Vero cells infected with either virus (named ICP0-CAT and Sph 6). For both recombinants, expression of CAT was not dependent upon prior viral protein synthesis. The kinetics of expression of CAT-specific mRNA resembled that of the HSV-1 genes into which CAT was inserted. Primer extension analysis revealed that the SV40 promoter is recognized and used when placed in cis in two different HSV-1 genome locations, and Northern hybridization experiments confirmed that the heterologous gene was expressed in the absence of prior viral protein synthesis. Therefore, this gene was not regulated as strictly as an HSV-1 gene, but was influenced by the environment into which it was placed, presumably by factors that are present when the normal viral gene is on.