Oral Tolerance Induced by Enterobacteria Altered the Process of Lymphocyte Recruitment to Intestinal Microvessels: Roles of Endothelial Cell Adhesion Molecules,TGF‐beta and Negative Regulators of TLR Signaling

Objective: Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)‐induced inflammatory conditions. Methods: Interaction of T‐cells with ileal microvessels was monitored by using an intravital microscope in mice under germ‐free (GF) and specific pathogen‐free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection. Results: Adherence of T‐cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T‐cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T‐cells in SPF mice. A significant induction of increase in mRNA expression of IRAK‐M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF‐beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment. Conclusions: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK‐M and TGF‐beta.     

Incremental Value of Objective Frailty Assessment to Predict Mortality in Elderly Patients Hospitalized for Heart Failure

Background

The impact of frailty on long-term prognosis in patients with heart failure (HF) remains unclear, and there is no simple and objective assessment for it. This study was performed to examine the association between frailty score and clinical outcome in elderly patients hospitalized for HF.

Modulation of intestinal immune system by dietary fat intake: Relevance to Crohn's disease

Gut-associated lymphoid tissue is the major inductive site of the mucosal immune system, which is functionally independent of the systemic immune system. Both the amount and type of dietary fat modulate intestinal immune function. Absorption of long-chain fatty acids stimulates lymphocyte flux and lymphocyte blastogenesis in intestinal lymphatics. Long-chain fatty acid absorption also significantly enhances migration of T lymphocytes to Peyer's patches, possibly due to up-regulation of adhesion molecules, such as α4-integrin and L-selectin. Lipoproteins are involved in stimulation of lymphocyte function by both receptor-dependent and independent mechanisms. However, unsaturated fatty acids at higher concentrations have a suppressive effect on cell-mediated immunity via eicosanoid release, receptor affinity changes or interactions with intracellular signal transduction. Fat absorption also influences various other cells in the intestinal mucosa: increased cytokine release from intestinal epithelial cells follows long-chain fatty acid absorption. In Crohn's disease, elemental diets and total parenteral nutrition often induce remission, possibly by reducing antigenic load on activated immune cells in the intestine and, thus, down-regulating hyperreactive CD4 cells. Dietary oleic acid supplements caused an immunological reversal effect in the intestinal immune system of animals fed an elemental diet. An excess of long-chain fatty acids in an elemental diet, therefore, may negate its beneficial effect on gut-associated lymphoid tissues in Crohn's disease. In contrast, supplemental dietary fish oil apparently tends to prevent relapse of Crohn's disease. Because dietary fat intake is closely associated with immunological function of the intestinal mucosa, careful manipulation of dietary fat can be important in management of this disease.     

Susceptibility genes for schizophrenia

Abstract  It is well known that genetic factors contribute to the susceptibility for schizophrenia. Recent advances in the molecular genetics of schizophrenia strongly suggest several susceptibility genes (e.g. dysbindin, neuregulin-1, DISC1, COMT, G72, RGS4 and Akt1). We discuss the evidence and biology of these genes. As glutamate transmission is especially implicated in these genes, neurobiological basis of schizophrenia might be elucidated by investigation of functional interactions between susceptibility genes for schizophrenia and the glutamatergic system.     

Detection of oral streptococci with collagen‐binding properties in saliva specimens from mothers and their children

International Journal of Paediatric Dentistry 2010; 20: 254–260 Background. Approximately 10–20% of Streptococcus mutans strains have been reported to possess collagen‐binding properties, whereas other species in the oral cavity with those properties remain to be elucidated. Aim. To identify strains with collagen‐binding properties and analyse their characteristics in comparison with S. mutans. Design. A total of 110 expectorated saliva specimens were collected from 55 pairs of mothers and their children. Bacterial strains with collagen‐binding properties were isolated and the species specified. In addition, strains with collagen‐binding properties isolated from mother–child pairs were analysed using molecular biological approaches. Results. The detection frequency of strains with collagen‐binding properties was shown to be 40.9%, among which S. salivarius was the most frequently detected, followed by S. mutans. The collagen‐binding activity of the S. mutans group was the highest, followed by S. salivarius. In addition, S. mutans and S. salivarius strains from 3 and 1 mother–child pairs, respectively, were shown to be the same clones. Conclusions. Our results indicate that S. mutans and S. salivarius are major species with collagen‐binding properties in the oral cavity, and that strains with such properties may be related to mother–child transmission.     

Current Treatment Results of Intracranial Carotid Artery Dissection Causing Cerebral Ischemia: A Japanese Nationwide Survey

Intracranial carotid artery dissection causing cerebral ischemia is a rare but important cause of cerebral infarction in children and adolescents. Although endovascular therapy has been reported to be effective, questions regarding the indications for intervention are yet to be addressed. Therefore, this study aimed to evaluate factors related to clinical outcomes through a nationwide survey. Overall, 35 neurosurgical centers reported patients within 2 weeks after ischemic onset due to intracranial carotid artery dissection causing cerebral ischemia treated between January 2015 and December 2020. Data on clinical and radiological findings were statistically analyzed. Twenty-eight patients met the inclusion criteria. The median age was 36 years (range, 7-59 years), without sex differences. Headache at onset was documented in 60.7% of the patients. Dissection findings were categorized into stenosis (71.4%) or occlusion (28.6%). Initial treatments, including various antithrombotic agent combinations in 23 (82.1%) patients, effectively improved or prevented aggravation in half of the patients. The patients with stenotic dissection were significantly more likely to experience aggravation during the initial treatment than did those with occlusive dissection (P = 0.03). In addition, the patients with moderate to severe neurological deficits on admission had poorer outcomes at discharge more frequently than did those with mild neurological deficits on admission. Eight patients undergoing endovascular therapy had no procedural complications or further aggravation after intervention. In conclusion, patients with intracranial carotid dissection causing cerebral ischemia who had a stenotic dissection were at risk of further aggravation, and endovascular therapy effectively improved or prevented aggravation.     

Effects of lansoprazole plus amoxycillin on the cure of Helicobacter pylori infection in Japanese peptic ulcer patients

Aim : The effect of lansoprazole plus amoxycillin on curing Helicobacter pylori infection and peptic ulcer recurrence was evaluated.
Method : The study group was composed of 68 patients with gastric ulcers and 51 with duodenal ulcers, all were H. pylori -positive. The participants were assigned at random to the lansoprazole alone group (lansoprazole 30 mg o.m. for 6 or 8 weeks) or the lansoprazole plus amoxycillin group (lansoprazole alone regimen plus amoxycillin at 500 mg q.d.s. concomitantly for the first 2 weeks). Healed patients were not given maintenance treatment with acid secretion inhibitors. The cure rate for H. pylori infection and the ulcer recurrence rate after 1 year were investigated.
Result : The cure rate for H. pylori infection was 4.2% in patients receiving lansoprazole alone and 38.5% in patients receiving lansoprazole plus amoxycillin ( P < 0.01) for gastric ulcers, and 0% in patients receiving lansoprazole alone and 61.9% in patients receiving lansoprazole plus amoxycillin ( P <0.001) for duodenal ulcers. The recurrence rate was 42.3% in patients receiving lansoprazole alone and 28.6% in patients receiving lansoprazole plus amoxycillin for gastric ulcers, and 66.7% for patients receiving lansoprazole alone and 11.1% for patients receiving lansoprazole plus amoxycillin ( P <0.001) for duodenal ulcers. None of the patients with gastric or duodenal ulcers cured of H. pylori infection had a recurrence.
Conclusion : Concomitant use of lansoprazole and amoxycillin increased the curative effects on H. pylori infection. However, the cure rates with this regimen remained inadequate.