Intrinsic nerves in the mammalian colon: confirmation of a plexus at the circular muscle-submucosal interface

Slow waves in the small intestine seem to arise in plexuses of neurites with interstitial cells of Cajal. In the colon, slow waves appear to arise at the circular muscle - submucosal interface. We therefore sought a plexus at this surface in the colon in the cat, dog, ferret, opossum, rabbit, rat, guinea-pig and man. Segments from all levels of the colon were stained by the Champy-Maillet osmic acid-zinc iodide method and cut into serial 25 micron sections in the plane of the muscle layers. A dense network of neurites with abundant interstitial cells of Cajal was found at the circular muscle - submucosal interface in all species except rabbit. Neurites in this plexus appeared to arise from the deep plexus of the submucosa (Schabadasch's or Henle's plexus). It was not found in the small intestine and stomach. A similar plexus was found in the interstices of the myenteric plexus in the colon. Interstitial cells of Cajal in both plexuses were positive for the NADH-diaphorase stain, but not for silver impregnation. The possible roles of the plexuses of neurites and interstitial cells of Cajal at the circular muscle - submucosal interface and at the plane of the myenteric plexus in the generation of rhythmic activity in the colon are discussed.     

Corticosteroids for the Enhancement of Fetal Lung Maturity: Impact on the Gravida with Preeclampsia and the HELLP Syndrome

Summary: This study was undertaken to determine maternal impact of corticosteroids administered for the promotion of fetal lung maturity in mothers with the HELLP syndrome. Twenty-seven of 427 women with the HELLP syndrome treated between 1980–1991 received a full course of steroids prior to preterm delivery. This group was compared to 27 matched control patients with the HELLP syndrome who received no corticosteroids. Subjects were matched for maternal age, race, sex of the fetus, and severity of the HELLP syndrome. The antepartum platelet count stabilized or increased in 25 of 27 steroid-treated women in contrast to 0 of 15 control women (p <0.00001). In comparison to control patients, LDH serum concentrations in steroid-treated patients stabilized or decreased and the SGOT/AST and SGPT/ALT stabilized or decreased during therapy (p < 0.005). The interval from delivery to platelet nadir in patients with Class III HELLP syndrome was shorter in the steroid-treated group (p<0.008) than in untreated patients.     

TNFα Inhibits Schwann Cell Proliferation, Connexin46 Expression, and Gap Junctional Communication

Schwann cell responses to nerve injury are stimulated, in part, by inflammatory cytokines. This study compares changes in the phenotype of cultured Schwann cells after exposure to the cytokine tumor necrosis factor (TNF)-α or the mitogen neu differentiation factor (NDF)-β. TNFα inhibited proliferation in a dose-dependent manner without altering Schwann cell survival. TNFα also reduced both gap junctional conductance and Lucifer yellow dye coupling between Schwann cells. Moreover, both P₀and glial fibrillary acidic protein (GFAP) immunoreactivity were reduced. By contrast, NDFβ initially had little effect on cell division although it reduced junctional coupling within 8 h. However, by 48 h, NDFβ stimulated proliferation with a concomitant increase in coupling. Dividing Schwann cells (BrdU⁺) were preferentially dye coupled compared to nondividing cells, indicating an association between proliferation and coupling. Moreover, cultured Schwann cells expressed connexin46 mRNA and protein, and changes in the levels of the protein correlated with the degree of proliferation and coupling. The data thus provide evidence for cytokine-induced modulation of Schwann cell antigenic phenotype, proliferation, and gap junction properties. These observations suggest that enhanced gap junctional communication among Schwann cells after nerve injury could help to coordinate cellular responses to the injury, and that TNFα may be a signal which terminates proliferation as well as junctional communication.     

Y chromosome loss in esophageal carcinoma: An in situ hybridization study

Carcinoma of the esophagus shows a strong male predominance and other epidemiologic differences from cancers arising at other sites. In this study, the prevalence of Y chromosome loss in 29 carcinomas of the esophagus and 53 carcinomas arising elsewhere in the aerodigestive tract was assessed by in situ hybridization of formalin-fixed paraffin-embedded tissue sections. Absence of the Y chromosome was defined as (1) negative staining for Y in neoplastic cells with positive staining for Y in immediately adjacent nonneoplastic epithelial and stromal cells, (2) positive staining of neoplastic cells with control probes for chromosomes X and 17, and (3) similar results at different stringencies and levels of protein digestion. According to these criteria, absence of the Y chromosome was observed in 13 of 14 (93%) adenocarcinomas of the esophagus, 8 of 13 (62%) squamous cell carcinomas of the esophagus, and 5 of 53 (9%) carcinomas arising in other sites. For the neoplasms examined, Y chromosome deletion was strongly and selectively associated with carcinomas, particularly adenocarcinomas, of the esophagus (P < .0001). These findings suggest that Y chromosome loss may be pathogenetically significant in these neoplasms. © 1993 Wiley-Liss, Inc.     

Effect of amiloride on electrolyte concentrations and rubidium uptake in principal and mitochondria-rich cells of frog skin

The role of mitochondria-rich cells (MR cells) in transepithelial Na transport was investigated by determining electrolyte concentrations and Rb uptake in individual cells of frog skin epithelium using electron microprobe analysis. Measurements were performed under control conditions and after blocking the transepithelial Na transport with amiloride. Under control conditions, Na and Cl concentrations of MR cells scattered much more than those of principal cells and ranged from a few up to more than 30 mmol/kg wet weight. Rb uptake from the basal side into individual MR cells also showed a large variation and was, on the average, much less pronounced than into the principal cells. In principal cells, amiloride reduced the Na concentration and Rb accumulation. In contrast, no effect was observed upon electrolyte concentration and Rb uptake of MR cells. Rb uptake was correlated to the Na concentration of MR cells both under control conditions and after amiloride. It is concluded that, in contrast to the principal cells, MR cells are not involved in amiloride-sensitive transepithelial Na transport and that their Na/K-pump activity is very low.     

Human figure drawing ability and vestibular processing dysfunction in learning-disabled children

Explored the relationship between vestibular function as measured by duration of postrotary nystagmus and human figure drawing ability in 40 children labeled as learning disabled. Regression analysis revealed that the variable of chronological age shared the most variance with human figure drawing scores. Postrotary nystagmus durations also shared a significant amount of variance with human figure drawing scores, while the variables of IQ and sex were nonsignificant. The results provide additional support for the assertion that some learning-disabled children evidence deficits in vestibular processing ability and that these deficits may affect performance on cognitive-perceptual tasks.     

The osmotic behaviour of toad skin epithelium (Bufo viridis)

The effect of saline adaptation on the intracellular Na, K, Cl, P concentrations and dry weight content of the toad skin epithelium (Bufo viridis) was studied using the technique of electron microprobe analysis. The measurements were performed on isolated abdominal skins either directly after dissection or after additional incubation in Ussing-type chambers.Adaptations of the toads to increasing NaCl concentrations for 7 days resulted in increased blood plasma osmolarity and a parallel increase in the cellular electrolyte, P and dry weight concentrations of the epithelium, the K increase representing the most significant fraction of the intracellular osmolarity increase. No evidence was obtained to show that the nucleus and cytoplasm reacted differently from each other and all living epithelial cell types basically showed the same response.Incubation of the isolated skins under control conditions showed a drastic inhibition of the transepithelial Na transport after adaptation to high salinities. In spite of the large variations in the transport rate almost identical intracellular electrolyte concentrations were observed. In tap water adapted toads the average cellular concentrations were 8.8 mmole/kg wet weight for Na, 109.6 for K, 41.5 for Cl, and 135.3 for P, respectively. Incubation of the skin with Ringer's solution of different osmolarities demonstrated that the epithelial cells are in osmotic equilibrium with the inner bathing solution. The results are consistent with the view that the osmotic adaptation is mainly accomplished by the movement of water.This work was supported by grants from the Deutsche Forschungsgemeinschaft and the Stiftung Volkswagenwerk     

LIT1 and H19 methylation defects in isolated hemihyperplasia

We performed LIT1 and H19 methylation studies on 27 children with isolated hemihyperplasia (IH). Eight children (29.6%) had a defect in methylation of one or both of these alleles, supporting our hypothesis that these epigenetic changes can result in a phenotype distinct from typical Beckwith-Wiedemann syndrome.     

Identification of vaccine candidate peptides in the NcSRS2 surface protein of Neospora caninum by using CD4+ cytotoxic T lymphocytes and gamma interferon-secreting T lymphocytes of infected holstein cattle

Previously, our laboratory showed that Holstein cattle experimentally infected with Neospora caninum develop parasite-specific CD4+ cytotoxic T lymphocytes (CTL) that lyse infected, autologous target cells through a perforin-granzyme pathway. To identify specific parasite antigens inducing bovine CTL and helper T-lymphocyte responses for vaccine development against bovine neosporosis, the tachyzoite major surface proteins NcSAG1 and NcSRS2 were targeted. In whole tachyzoite antigen-expanded bovine T-lymphocyte lines, recombinant NcSRS2 induced potent memory CD4+- and CD8+-T-lymphocyte activation, as indicated by proliferation and gamma interferon (IFN-gamma) secretion, while recombinant NcSAG1 induced a minimal memory response. Subsequently, T-lymphocyte epitope-bearing peptides of NcSRS2 were mapped by using overlapping peptides covering the entire NcSRS2 sequence. Four experimentally infected cattle with six different major histocompatibility complex (MHC) class II haplotypes were the source of immune cells used to identify NcSRS2 peptides presented by Holstein MHC haplotypes. NcSRS2 peptides were mapped by using IFN-gamma secretion by rNcSRS2-stimulated, short-term T-lymphocyte cell lines, IFN-gamma enzyme-linked immunospot (ELISPOT) assay with peripheral blood mononuclear cells, and 51Cr release cytotoxicity assay of rNcSRS2-stimulated effector cells. Four N. caninum-infected Holstein cattle developed NcSRS2 peptide-specific T lymphocytes detected ex vivo in peripheral blood by IFN-gamma ELISPOT and in vitro by measuring T-lymphocyte IFN-gamma production and cytotoxicity. An immunodominant region of NcSRS2 spanning amino acids 133 to 155 was recognized by CD4+ T lymphocytes from the four cattle. These findings support investigation of subunit N. caninum vaccines incorporating NcSRS2 gene sequences or peptides for induction of NcSRS2 peptide-specific CTL and IFN-gamma-secreting T lymphocytes in cattle with varied MHC genotypes.