Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.
Patients often cite lack of retention and poor aesthetics as reasons for not wearing their partial dentures. Traditional metal alloy clasps have been shown to exert forces on abutment teeth that exceed those capable of producing tooth movement. In addition, metal display on anterior teeth is often unacceptable. The technopolymer materials are purported to have superior flexibility and exert less force than the metals. This study compared the flexibility and forces produced by technopolymer clasps with those exerted by cobalt-chromium and titanium clasps. The results showed that the technopolymer clasps were up to ten times as flexible as the metal clasps, and they returned to their pretest dimensions after being stretched. In addition, they exerted forces on the abutment teeth that fall within the range of those considered safe for use. This coupled with their pleasing aesthetics makes them suitable for use on periodontally compromised teeth, those with deep undercuts and on anterior teeth. 相似文献
Despite improved resolution with new imaging techniques, surgical confirmation of mediastinal lymph node status is often required for reliable staging of patients with non-small cell lung cancer. Recent scintigraphic studies suggest that s.c. administration of radiolabeled antibodies can be more efficient than the i.v. route for targeting regional lymph nodes in animals and humans. To determine if this approach could be applied to the lymphatics of the lung, we injected both specific and irrelevant radiolabeled monoclonal antibodies via a flexible fiberoptic bronchoscope through the mucosa of lobar bronchi in normal dogs. The injected antibodies were expected to drain by way of local lymphatic vessels toward the central lymph nodes, in effect following the same pathway as do cells metastasizing to these nodes during early regional tumor dissemination. To accomplish this, anesthetized dogs were intubated and then coinjected with the two labeled antibodies [600 microCi/100 micrograms (total)] through a fiberoptic bronchoscope. The animals were serially imaged and then autopsied 14-36 h after injection. Individual hilar and carinal nodes contained over 1% of the injected 131I-labeled specific antibody dose and the average selectivity was 2.5:1 with respect to a coinjected irrelevant IgG. Distant organs (mesenteric lymph node, liver, spleen, bone marrow, and lung parenchyma other than the injection site) contained much less radioactivity, and those sites accumulated a greater fraction of the non-specific labeled antibody. The ratio of iodine-131 to iodine-125 counts between hilar/carinal lymph nodes and abdominal lymph nodes ranged from 15:1 to 100:1. These initial studies indicate efficient delivery of antibody to a subset of the regional nodes via pulmonary lymphatics. They suggest the feasibility of this technique which may be of use in the detection and perhaps therapy of human lung cancer metastases in regional lymph nodes. 相似文献
It is generally agreed that use of aftercare services following discharge from alcoholism treatment is optimum for patients to achieve long-term recovery. However, the quantity and duration of utilization of such services in non-experimental settings are generally unknown. Using secondary data sources, we studied 5,635 alcoholics completing formal extended inpatient treatment and 1,860 alcoholics discharged from brief inpatient hospitalizations in Department of Veterans Affairs medical centers. Weekly use of outpatient mental health services (OPMH) prior to hospital admission was equally low for both patient groups (approximately 2-3% of patients) until four weeks prior to admission, at which time OPMH use increased, particularly for the extended treatment group. In the four weeks after discharge, use of OPMH services was substantially higher for patients with extended treatment compared to those with brief hospitalizations (40% vs. 18%), with 22% of patients completing treatment utilizing such services in the first week after discharge. Utilization steadily decreased until only 8% and 4% of both groups, respectively, were using OPMH services at the end of six months after discharge. Study results suggest the need to examine barriers to outpatient mental health utilization after discharge as well as interventions to increase compliance with long-term aftercare. 相似文献
Human adenocarcinoma (AC) is the most frequently diagnosed human lung cancer, and its absolute incidence is increasing dramatically. Compared to human lung AC, the A/J mouse-urethane model exhibits similar histological appearance and molecular changes. We examined the gene expression profiles of human and murine lung tissues (normal or AC) and compared the two species' datasets after aligning approximately 7500 orthologous genes. A list of 409 gene classifiers (P value <0.0001), common to both species (joint classifiers), showed significant, positive correlation in expression levels between the two species. A number of previously reported expression changes were recapitulated in both species, such as changes in glycolytic enzymes and cell-cycle proteins. Unexpectedly, joint classifiers in angiogenesis were uniformly down-regulated in tumor tissues. The eicosanoid pathway enzymes prostacyclin synthase (PGIS) and inducible prostaglandin E(2) synthase (PGES) were joint classifiers that showed opposite effects in lung AC (PGIS down-regulated; PGES up-regulated). Finally, tissue microarrays identified the same protein expression pattern for PGIS and PGES in 108 different non-small cell lung cancer biopsies, and the detection of PGIS had statistically significant prognostic value in patient survival. Thus, the A/J mouse-urethane model reflects significant molecular details of human lung AC, and comparison of changes in orthologous gene expression may provide novel insights into lung carcinogenesis. 相似文献
Vascularization is a prominent event during corpus luteum formation,
providing low density lipoproteins for steroid biosynthesis and enabling
transport of secreted steroids. The process of vascularization is
controlled by specific regulators. Vascular endothelial growth factor
(VEGF), otherwise named vascular permeability factor (VPF), induces
endothelial cell proliferation as well as angiogenesis in vivo and
increases capillary permeability. Here we report the expression of VEGF/VPF
mRNA by cultured human luteinized granulosa cells (GC) for at least 10
days. Without HCG VEGF/VPF expression declined after day 4 and by day 10
was reduced to approximately 30% of the value at day 4. However, after
culture in the presence of 1 U/ml human chorionic gonadotrophin (HCG),
expression of VEGF/VPF mRNA by GC was four times greater than control
experiments by day 10, and increased 100% from day 4 to day 10.
Simultaneously, HCG supplementation increased VEGF/VPF secretion by GC.
Medium VEGF/VPF on day 3 was 13 pM without and 11 pM with HCG. Medium
VEGF/VPF on day 10 was 6 pM without HCG and 29 pM with HCG. These results
suggest that vascularization of the corpus luteum is induced by
HCG-mediated effects of VEGF/VPF.
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