Autonomic regulation of experimental autoimmune encephalomyelitis in IL-4 knockout mice

The effect of chemical sympathectomy induced with 6-hydroxydopamine (OHDA) on experimental autoimmune encephalomyelitis (EAE) was studied in wild type and IL-4^−/− C57BL/6 (B6) mice. When actively sensitized with myelin oligodendrocyte glycoprotein (MOG)_35–55 peptide, control B6 mice developed a mild form of EAE with full recovery. The sympathectomized mice developed paralysis with higher maximum disease score and did not recover completely, indicating that the sympathetic nervous system (SNS) down-modulates the process of EAE. Unexpectedly, however, sympathectomy resulted in suppression of EAE in IL-4^−/− mice, implying that control of actively induced EAE by the SNS depends on the genetic background of mice. We also induced EAE by passive transfer of MOG_35–55-reactive lymph node cells, and this disease was augmented by sympathectomy in both wild type and knockout animals. Further experiments showed that changes in T cell populations and the activity of antigen presenting cells might be responsible for the altered immune response and clinical course after sympathetic ablation. Our studies indicate that the absence of a single cytokine can severely alter nervous–immune system interactions.     

Recent trends in the clinical practice of nutritional support in Japan: results of a national survey carried out in 2001

Nutritional support has advanced and patients can now be given more effective nutritional care. On the other hand, some problems remain, such as inadequate administration of total parenteral nutrition (TPN), catheter-related sepsis, etc. The Committee of the National Survey on Nutritional Support, established under the Japanese Society for Parenteral and Enteral Nutrition, investigated the recent trends in the clinical practice of nutritional support in Japan by mailing a questionnaire containing 90 questions to a total of 6,500 physicians in 10 medical departments. The results showed that: 1) surgeons have more interest in nutritional support than physicians in other fields. 2) More than 90% of physicians in Japan still use intravenous hyperalimentation(IVH) instead of TPN and they place more focus on the central venous catheter and insertion of the central venous catheter than on hyperalimentation in the term IVH. 3) There remains a tendency for surgeons to prefer parenteral nutrition to enteral nutrition. This tendency is supported by data showing that the rate of administering TPN to gastroenterological surgical patients as a postoperative management method is high. To the question, "How did you learn about nutritional support?," only 18.3% of physicians answered that they studied it in medical school. We may conclude this to be the most important problem in nutritional support in Japan.     

Microtubule associated protein (tau) gene variability in patients with frontotemporal dementia

Frontotemporal dementia represents up to 10% of all dementias and is, next to Alzheimer's disease and Lewy body disease, the third most common cause of degenerative dementia. The term "frontotemporal dementia" covers a range of conditions, including Pick's disease, frontal lobe degeneration and dementia associated with motor neurone disease. Neuropathologically FTD is characterised by atrophy of the frontal and temporal lobes of the cerebral cortex, often with additional subcortical changes. Both familial and more frequently sporadic forms of FTD can be recognised. Recently, mutations in the microtubule-associated protein (tau) gene have been found in families with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). The identification of mutations in the tau gene indicates that the protein plays a central role in the process of neurodegeneration. Epidemiology of frontotemporal dementias in Poland remains still unknown. A prevalence of tau mutations among Polish patients has not been established yet. Here, we report results of a mutational analysis of the tau gene among Polish FTD patients. No pathogenic mutation was found in the analysed sample. The study confirmed that the frequency of tau mutations is very low and depends strongly on the clinical criteria used to select patients. Mutations in the tau gene account only for a small number of FTD cases with a clear autosomal dominant pattern of disease inheritance. Therefore there should exist additionalgenetic and non-genetic factors contributing to the pathogenesis of both familial (linked and non-linked to chromosome 17) and sporadic forms of FTD.     

Neuroblastoma x spinal cord (NSC) hybrid cell lines resemble developing motor neurons.

We have developed a series of mouse-mouse neural hybrid cell lines by fusing the aminopterin-sensitive neuroblastoma N18TG2 with motor neuron-enriched embryonic day 12-14 spinal cord cells. Of 30 neuroblastoma-spinal cord (NSC) hybrids displaying a multipolar neuron-like phenotype, 10 express choline acetyltransferase, and 4 induce twitching in cocultured mouse myotubules. NSC-19, NSC-34, and their subclones express additional properties expected of motor neurons, including generation of action potentials, expression of neurofilament triplet proteins, and acetylcholine synthesis, storage, and release. In addition, NSC-34 cells induce acetylcholine receptor clusters on cocultured myotubes, and undergo a vimentin-neurofilament switch with maturation in culture, similar to that occurring in neuronal development. NSC cell lines appear to model selected aspects of motor neuron development in an immortalized clonal system.     

Abrogation of spleen macrophage suppressive activity by 15-deoxyspergualin

We studied the immunomodulatory mechanism of 15-deoxyspergualin (DSG), a novel antitumor agent. To assess this, we used a mixed culture of antigen-primed lymph node cells (LNC) and spleen cells (SPC). In normal or untreated conditions, SPC suppressed the proliferative response of LNC to the antigens. In contrast, SPC from DSG-treated animals did not show any suppressive activity. This suppression was mediated by adherent cells in SPC but the suppression mechanism was recovered when DSG-treated spleen macrophages were reconstituted with control spleen nonadherent cells. These data suggest that DSG abrogates nonspecific suppressive activity of spleen cells by acting on both adherent and nonadherent cells.     

Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes

Liver-expressed chemokine (LEC)/CCL16 is a human CC chemokine selectively expressed in the liver. Here, we investigated its receptor usage by calcium mobilization and chemotactic assays using mouse L1.2 pre-B cell lines stably expressing a panel of 12 human chemokine receptors. At relatively high concentrations, LEC induced calcium mobilization and chemotaxis via CCR1 and CCR2. LEC also induced calcium mobilization, but marginal chemotaxis via CCR5. Consistently, LEC was found to bind to CCR1, CCR2 and CCR5 with relatively low affinities. The binding of LEC to CCR8 was much less significant. In spite of its binding to CCR5, LEC was unable to inhibit infection of an R5-type HIV-1 to activated human peripheral blood mononuclear cells even at high concentrations. In human liver sections, hepatocytes were strongly stained by anti-LEC antibody. HepG2, a human hepatocarcinoma cell line, was found to constitutively express LEC. LEC was also present in the plasma samples from healthy adult donors at relatively high concentrations (0.3--4 nM). Taken together, LEC is a new low-affinity functional ligand for CCR1, CCR2 and CCR5, and is constitutively expressed by liver parenchymal cells. The presence of LEC in normal plasma at relatively high concentrations may modulate inflammatory responses.     

Recognition of alloantigens and induction of experimental allergic encephalomyelitis by a murine encephalitogenic T cell clone

In this communication we report a SJL/J (H-2s, Mlsc)-derived encephalitogenic T cell clone 4b.14a which has dual specificities for myelin basic protein/I-As and allogeneic H-2Ik gene products. Monoclonal antibodies specific for public class II major histocompatibility complex (MHC) determinants (Ia.17, I-Ak, r and Ia.7) and anti-L3T4 antibody inhibited the response of the clone 4b.14a to alloantigens, but a monoclonal antibody specific for a private determinant on I-Ak (Ia.2) did not inhibit the response. Although this clone proliferated in response to allogeneic spleen cells expressing H-2Ik determinants regardless of disparate Mlsa, b, c, d alleles, CBA/N cells (H-2k, Mlsnull) failed to stimulate the clone 4b.14a. These results suggest that recognition of allogeneic class II MHC molecules by this clone requires recognition with non-MHC gene products such as Mls. In addition, the clone 4b.14a stimulated by alloantigens could mediate clinical signs of experimental allergic encephalomyelitis in syngeneic recipients. However, interleukin 2 of rat spleen cell origin alone failed to activate the clone cells to make them encephalitogenic, though it could make them proliferate. The significance of these findings for T cell recognition and activation is discussed.     

Evaluation of oxygen consumption and resting energy expenditure in critically ill patients with systemic inflammatory response syndrome.

OBJECTIVE: To determine whether oxygen consumption VO2), CO2 production, and resting energy expenditure (REE) in critically ill patients differ in varying grades of systemic inflammatory response syndrome (SIRS). DESIGN: Prospective, clinical study. SETTING: Intensive care unit at a university hospital. PATIENTS: Twenty-six critically ill patients requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 100 metabolic measurements were performed. The grade of SIRS and the Acute Physiology and Chronic Health Evaluation II score were evaluated at the time of the metabolic cart study. VO2 and REE differed among the groups inadequate for SIRS (non-SIRS), with SIRS without infection (nonseptic SIRS), and with SIRS with infection (septic SIRS) (125 +/- 37 mL/min/m2 and 855 +/- 204 kcal/day/m2, 135 +/- 33 mL/min/m2 and 948 +/- 214 kcal/day/m2, and 166 +/- 55 mL/min/m2 and 1149 +/- 339 kcal/day/m2, respectively; p < .005). Patients with septic SIRS had higher VO2 and REE than patients with non-SIRS and nonseptic SIRS. CONCLUSION: VO2 and REE differ among groups of patients with non-SIRS, nonseptic SIRS, and septic SIRS. Patients with septic SIRS have higher VO2 and REE than patients with non-SIRS or nonseptic SIRS. The present study shows that classifying patients into three grades (non-SIRS, nonseptic SIRS, and septic SIRS) is a valid predictor of metabolic stress in critically ill patients.     

Isolated colonic hernia through the esophageal hiatus

We report on a 75-year-old woman with an isolated colonic hernia through the esophageal hernia. The patient had suffered from cough, palpitation and dyspnea. A chest X-ray showed a colon loop gas in the mediastinum. Simultaneous barium swallow and enema showed the herniation of the only transverse colon into the mediastinum and displacement of the distal esophagus by the migrated colon. The patient underwent an open-mesh cruroplasty and a Hill's posterior gastropexy. The postoperative clinical course was uneventful. The patient has cessation of the symptoms. To our knowledge, there are only five reports presenting patients with isolated colonic hernia through the esophageal hiatus, including our case.     

Parvalbumin-immunoreactive neurons in the human central nervous system are decreased in Alzheimer's disease

Summary Immunohistochemical localization of the Ca²⁺-binding protein parvalbumin (PV) was investigated in the adult human central nervous system (CNS). The antiserum against purified rat skeletal muscle PV specifically recognized certain neuronal populations and their processes. Strongly positive were Purkinje, basket and stellate cells of the cerebellum, cerebral cortical nonpyramidal cells, and neurons in the thalamic reticular and ventrolateral nuclei, subthalamic nucleus, lateral and medial geniculate bodies, vestibular and cochlear nuclei, spinal trigeminal nucleus, cuneate and gracile nuclei, and dorsal nucleus of Clarke. Negative were cortical pyramidal neurons, neurons of the autonomic nerves, and neurons in the caudate nucleus, putamen, dentate nucleus, inferior olive, and substantia gelatinosa. The number and size of PV-immunoreactive neurons were significantly decreased in Alzheimer's disease. However, the decrease was not disease specific.