Receptors for Treponema pallidum attachment to the surface and matrix proteins of cultured human dermal microvascular endothelial cells

Pathogenicity of Treponema pallidum may depend upon the binding of Treponema pallidum to matrix proteins, especially to fibronectin. Infectious organism or cell to matrix interactions are mediated by a family of adhesion molecule receptors known as integrins. Once in the host, the pathogenic Treponema pallidumdum adheres to the vascular endothelium and readily penetrates surrounding tissues. Fibronectin plays an important role in the mediation of the attachment of Treponema pallidum to host cells, including endothelial cells. We found that the binding of Treponema pallidum to human dermal microvascular endothelial cells and to a glass surface coated with fibronectin is inhibited by the presence of arginine-glycine- aspartic acid (RGD), and analysis of the surface receptor revealed an antigenic similarity to an integrin molecule, namely alpha5. This ability to adhere to host endothelium and fibronectin is quite unique to T. pallidum among the treponemes, and may be a key pathogenic factor.     

PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted,but Functional in Patients with COVID-19

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Bronchoalveolar lavage cytokine profiles in acute asthma and acute bronchiolitis

BACKGROUND: The pathogenetic basis for the relationship between acute bronchiolitis and asthma has not yet been completely elucidated. OBJECTIVE: The aim of this study was to compare these 2 diseases in terms of their patterns of airway cytokine response (T(H)1 or T(H)2). METHODS: By using a bronchoalveolar lavage (BAL) technique, this study investigated the cytokine levels of BAL fluid in children with acute asthma who had no identifiable respiratory syncytial virus (RSV) infection (n = 18) and in infants with acute bronchiolitis caused by RSV (n = 22). Comparisons were made with normal control subjects (n = 14). IFN-gamma (T(H)1) and IL-4 and IL-5 (T(H)2) levels were measured in concentrated BAL fluids by means of ELISA. RESULTS: The IL-5 level (P <.001) and IL-5/IFN-gamma ratio (P <.001) were significantly increased in the asthmatic group with no identifiable RSV infection and in the RSV-induced bronchiolitis group compared with values in the control group. When infants in the bronchiolitis group were divided into eosinophil-positive and eosinophil-negative subgroups, the eosinophil-positive subgroup had significantly increased IL-5 levels (P <.001) and IL-5/IFN-gamma ratios (P <.01) compared with those in the control group, but similar cytokine responses were not induced in the eosinophil-negative subgroup. The percentage of BAL eosinophils correlated significantly with levels of BAL IL-5 in both the asthma group (r = 0.80, P =.000) and the bronchiolitis group (r = 0.82, P =.000). CONCLUSIONS: These findings suggest that a subgroup of the RSV-induced bronchiolitis group results in a T(H)2-type response, and this could provide a valuable framework to explain the link between RSV-induced bronchiolitis and asthma.     

Cloning and developmental expression analysis of the murine homolog of the spinocerebellar ataxia type 1 gene (Sca1)

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat which encodes glutamine in the novel protein ataxin-1. In order to characterize the developmental expression pattern of SCA1 and to identify putative functional domains in ataxin-1, the murine homolog (Sca1) was isolated. Cloning and characterization of the murine Sca1 gene revealed that the gene organization is similar to that of the human gene. The murine and human ataxin-1 are highly homologous but the CAG repeat is virtually absent in the mouse sequence suggesting that the polyglutamine stretch is not essential for the normal function of ataxin-1 in mice. Cellular and developmental expression of the murine homolog was examined using RNA in situ hybridization. During cerebellar development, there is a transient burst of Sca1 expression at postnatal day 14 when the murine cerebellar cortex becomes physiologically functional. There is also marked expression of Sca1 in mesenchymal cells of the intervertebral discs during development of the spinal column. These results suggest that the normal Sca1 gene, has a role at specific stages of both cerebellar and vertebral column development.      

PAC and Cosmid Contig Spanning the HOXA Cluster on Human Chromosome 7p15

To construct the PAC and cosmid contig map spanning the HOXA cluster on human chromosome 7, we used 9 DNA markers (D7S2243, D7S3010, HOXA1, EVX1, 750, pBH8, p60, p8.0, and HOXA11), among which the final 4 were generated in this study by shotgun cloning strategy. From the libraries, 5 PAC and 35 cosmid clones were screened and as a result, an overlapping continuous array of cosmid and PAC clones covering the genomic region (about 200 kb) spanning the entire cluster were constructed. The isolated cosmids contained several consecutive HOX genes of regional group, probably sharing the regulatory processes such as alternative splicing or polyadenylation, and thus could be used as useful materials for elucidating the molecular mechanism of HOX gene expression in the future.     

Alterations in extracellular matrix components in transplant glomerulopathy

The distribution pattern of extracellular matrix (ECM) components in transplant glomerulopathy was studied in relation to light microscopic features, actin expression of mesangial cells, and intraglomerular inflammatory cells. Nine cases of mild (group I) and nine cases of severe (group II) transplant glomerulopathy were stained with antisera against fibronectin (FN), tenascin (TN), collagen types III and IV, smooth muscle actin, CD45RO, CD68, and Ki-67 antigen. The composition of ECM was similar in the two groups. The expanded mesangium was diffusely stained by type-IV collagen, FN and TN, and focally and weakly stained by type-III collagen and smooth muscle actin. Type-IV collagen was linearly stained along the capillary walls, imparting a double-contour feature, whereas FN and TN showed granular staining along the capillary walls. CD68 positive cells were increased in severe transplant glomerulopathy, but this increase was not related to ECM deposition. These findings suggest that increased glomerular deposition of normal and abnormal ECM components participate in the evolution of transplant glomerulopathy. Received: 5 October 1999 / Accepted: 17 January 2000     

Objective stress monitoring based on wearable sensors in everyday settings

Abstract

Monitoring people’s stress levels has become an essential part of behavioural studies for physical and mental illnesses conducted within the biopsychosocial framework. There have been several stress assessment studies in laboratory-based controlled settings. However, the results of these studies do not always translate effectively to an everyday context. The current state of wearable sensor technology allows us to develop systems measuring the physiological signals reflecting stress 24/7 while capturing the context. In this paper, we present a stress monitoring system that provides objective daily stress measurements in everyday settings based on three physiological signals: electrocardiogram (ECG), photoplethysmogram (PPG), and galvanic skin response (GSR) using Shimmer3 ECG, Shimmer3 GSR+, and Empatica E4 wearable sensors. We perform controlled stress assessment experiments on 17 participants in which we successfully detect stress with a 94.55% accuracy for 10-fold cross-validation and an 85.71% accuracy for subject-wise cross-validation. In everyday settings, the system assesses stress with an 81.82% accuracy. We also examine whether motion artefacts affect stress assessment and filter the low-confidence readings to minimise false alarms.     

Immunogenicity and Safety of Two Different Haemophilus influenzae Type b Conjugate Vaccines in Korean Infants

The incidence of invasive diseases, including meningitis caused by Haemophilus influenzae type b (Hib) was markedly decreased after routine immunization of Hib vaccine through diverse schedules in many countries. The purpose of this study was to evaluate the immunogenicity and safety of Hib conjugate vaccines in Korean children before the implementation of a national immunization program against Hib in Korea. A multicenter controlled trial was performed on two different Hib vaccines in Korean children. A total of 319 infants were enrolled: 199 infants were immunized with the Hib polysaccharide conjugated to the tetanus toxoid (PRP-T) and 120 infants with the Hib polysaccharide conjugated to the outer-membrane protein of Neisseria meningitides (PRP-OMP). Immunogenicity was evaluated by enzyme-linked immunosorbent assay (ELISA) and serum bactericidal assay. Both vaccines showed good immunologic responses after primary immunization. After 2 doses of PRP-T or PRP-OMP, 78.9% and 91.7% of infants achieved an antibody level of ≥1.0 µg/mL, respectively. Both vaccines were safe and well-tolerated. No serious adverse events were observed. Thus, Hib conjugate vaccines appear to be safe and show good immunogenicity in Korean infants. These results will be important reference data for the implementation of Hib vaccine in the national immunization program of Korea.     

Effect of ketamine on apoptosis by energy deprivation in astroglioma cells using flow cytometry system

Apoptosis is a programmed, physiologic mode of cell death that plays an important role in tissue homeostasis. As for the central nervous system, ischemic insults can induce pathophysiologic cascade of apoptosis in neurophils. Impairment of astrocyte functions during brain ischemia can critically influence neuron survival by neuronglia interactions. We aimed to elucidate the protective effect of ketamine on apoptosis by energy deprivation in astrocytes. Ischemic insults was induced with iodoacetate/ carbonylcyanide m-chlorophenylhydrazone (IAA/CCCP) 1.5 mM/20 microm or 150 microm/2 microm for 1 hr in the HTB-15 and CRL-1690 astrocytoma cells. Then these cells were reperfused with normal media or ketamine (0.1 mM) containing media for 1 hr or 24 hr. FITC-annexin-V staining and propidium iodide binding were determined by using flow cytometry. Cell size and granularity were measured by forward and side light scattering properties of flow cytometry system, respectively. An addition of ketamine during reperfusion increased the proportion of viable cells. Ketamine alleviated cell shrinkage and increased granularity during the early period, and ameliorated cell swelling during the late reperfusion period. Ketamine may have a valuable effect on amelioration of early and late apoptosis in the astrocytoma cells, even though the exact mechanism remains to be verified.