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Simultaneous primary malignancy of the lung and kidney has been rarely recognized during life. Three patients with synchronous primary pulmonary and renal cancer are described. The pulmonary tumors were asymptomatic and were discovered on plain chest roentgenography. The renal tumors, also asymptomatic, were incidentally discovered on CT, performed for staging. Although one patient was treated with interleukin-2 for a presumed solitary pulmonary metastasis from renal carcinoma, in all three patients, both the kidney and lung tumors were eventually removed either concurrently or sequentially. Prior autopsy case series are reviewed. In the elderly, synchronous asymptomatic pulmonary and renal malignancy is not surprising, and it should be approached as a distinct clinical problem. With the use of chest roentgenography for screening high risk populations and CT for staging, simultaneous primary pulmonary and renal malignancy will probably be recognized increasingly. 相似文献
23.
Brian D. Adkins Theresa A. Libby Marlene M. Mayberry Thomas W. Brady Justin B. Halls Stephanie Mallow Corbett Joseph Schoeny Eric P. Shields Jahan Chowdhury Amanda N. Kinsinger-Stickel Gay Wehrli Nicholas R. Jaeger Matthew P. Robertson Kathy M. Butler Stuart M. Lowson James Forrest Calland James D. Gorham 《Transfusion》2021,61(11):3066-3074
24.
Matthew B. Harms Janet Cady Craig Zaidman Paul Cooper Taha Bali Peggy Allred Carlos Cruchaga Michael Baughn Ryan T. Libby Alan Pestronk Alison Goate John Ravits Robert H. Baloh 《Neurobiology of aging》2013
Hexanucleotide repeat expansions in C9ORF72 are a common cause of familial and apparently sporadic amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The mechanism by which expansions cause neurodegeneration is unknown, but current evidence supports both loss-of-function and gain-of-function mechanisms. We used pooled next-generation sequencing of the C9ORF72 gene in 389 ALS patients to look for traditional loss-of-function mutations. Although rare variants were identified, none were likely to be pathogenic, suggesting that mutations other than the repeat expansion are not a common cause of ALS, and providing supportive evidence for a gain-of-function mechanism. We also show by repeat-primed PCR genotyping that the C9ORF72 expansion frequency varies by geographical region within the United States, with an unexpectedly high frequency in the Mid-West. Finally we also show evidence of somatic instability of the expansion size by Southern blot, with the largest expansions occurring in brain tissue. 相似文献
25.
Ilanit Hasson-Ohayon Steven de Jong Libby Igra Sarah A. Carter Laura A. Faith Paul Lysaker 《Clinical psychology & psychotherapy》2021,28(5):1243-1253
Although the clinical significance of therapeutic alliance with people with psychosis is well established, the agreement between client and therapist assessments of therapeutic alliance and the longitudinal changes of both assessments have been rarely addressed. The current study examined client and therapist assessments of therapeutic alliance longitudinally and sought to determine whether insight and severity of symptoms moderated the degree to which therapist and client assessments were in agreement with one another. Forty-five participants diagnosed with a schizophrenia spectrum disorder and their therapists were administered a therapeutic alliance questionnaire (Working Alliance Inventory-Short Form) monthly for 6 months. Baseline symptoms were assessed using the PANSS. Results did not produce evidence that insight into illness moderated the relationship between agreement on the therapeutic alliance. However, symptoms of emotional discomfort at baseline predicted differences in agreement between clients and therapists on the relationship aspect of therapeutic alliance over the course of therapy. These results suggest that the ability to express symptoms of emotional discomfort may affect whether clients and therapists form similar appraisals of the strength of the therapeutic alliance. 相似文献
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Sukhova GK Wang B Libby P Pan JH Zhang Y Grubb A Fang K Chapman HA Shi GP 《Circulation research》2005,96(3):368-375
The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves substantial proteolysis of the arterial extracellular matrix. The lysosomal cysteine proteases can exert potent elastolytic and collagenolytic activity. Human atherosclerotic plaques have increased cysteine protease content and decreased levels of the endogenous inhibitor cystatin C, suggesting an imbalance that would favor matrix degradation in the arterial wall. This study tested directly the hypothesis that impaired expression of cystatin C alters arterial structure. Cystatin C-deficient mice (Cyst C-/-) were crossbred with apolipoprotein E-deficient mice (ApoE-/-) to generate cystatin C and apolipoprotein E-double deficient mice (Cyst C-/-ApoE-/-). After 12 weeks on an atherogenic diet, cystatin C deficiency yielded significantly increased tunica media elastic lamina fragmentation, decreased medial size, and increased smooth muscle cell and collagen content in aortic lesions of ApoE-/- mice. Cyst C-/-ApoE-/- mice also showed dilated thoracic and abdominal aortae compared with control ApoE-/- mice, although atheroma lesion size, intimal macrophage accumulation, and lipid core size did not differ between these mice. These findings demonstrate directly the importance of cysteine protease/protease inhibitor balance in dysregulated arterial integrity and remodeling during experimental atherogenesis. 相似文献
28.
Geographical coincidence of high heat flow, high seismicity, and upwelling, with hydrocarbon deposits, phosphorites, evaporites, and uranium ores 下载免费PDF全文
Libby LM Libby WF 《Proceedings of the National Academy of Sciences of the United States of America》1974,71(10):3931-3935
Oil deposits occur in deep sediments, and appear to be organic matter that has been transformed through the action of geothermal heat and pressure. Deep sediments, rich in biological remains, are created by ocean upwelling, caused in part by high geothermal heat flow through the sea bottom. Such regions correlate with enhanced seismic activity. We look for correlations of seismicity, high heat flux, petroleum, uranium, phosphates, and salts, deposited from abundant plant life. These may be useful in discovering more petroleum and coal. We estimate that the known world reserves of petroleum and coal are about 10-4 of the total of buried biogenic carbon. 相似文献
29.
Brendan M. Everett Marc Y. Donath Aruna D. Pradhan Tom Thuren Prem Pais Jose C. Nicolau Robert J. Glynn Peter Libby Paul M Ridker 《Journal of the American College of Cardiology》2018,71(21):2392-2401
Background
Subclinical inflammation mediated in part by interleukin (IL)-1β participates in peripheral insulin resistance and impaired pancreatic insulin secretion.Objectives
The authors tested the hypothesis that the IL-1β inhibitor canakinumab reduces incident diabetes.Methods
The authors randomized 10,061 patients with prior myocardial infarction and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/l to placebo or canakinumab at doses of 50 mg, 150 mg, or 300 mg subcutaneously once every 3 months. The authors tested the effects of canakinumab on major cardiovascular events in patients with and without diabetes at baseline, and evaluated as a pre-specified analysis whether canakinumab would reduce the risk of adjudicated cases of new-onset type 2 diabetes among those with protocol-defined pre-diabetes at trial entry. The authors also evaluated the effect of canakinumab on fasting plasma glucose and glycosylated hemoglobin (HbA1c) in patients with and without established diabetes.Results
Of the participants, 4,057 (40.3%) had baseline diabetes, 4,960 (49.3%) had pre-diabetes, and 1,044 (10.4%) had normal glucose levels. Among those without diabetes, increasing tertiles of hsCRP at baseline associated with an increased risk of developing diabetes during the median follow-up period of 3.7 years (incidence rates 3.2, 4.1, and 4.4 per 100 person-years; p = 0.003). Canakinumab 150 mg as compared with placebo had similar magnitude effects on major cardiovascular event rates among those with diabetes (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.70 to 1.03), pre-diabetes (HR: 0.86; 95% CI: 0.70 to 1.06), and normoglycemia (HR: 0.81; 95% CI: 0.49 to 1.35). Despite large reductions in hsCRP and IL-6, canakinumab did not reduce the incidence of new-onset diabetes, with rates per 100 person-years in the placebo, 50 mg, 150 mg, and 300 mg canakinumab groups of 4.2, 4.2, 4.4, and 4.1, respectively (log-rank p = 0.84). The HR comparing all canakinumab doses to placebo was 1.02 (95% CI: 0.87 to 1.19; p = 0.82). Canakinumab reduced HbA1c during the first 6 to 9 months of treatment, but no consistent long-term benefits on HbA1c or fasting plasma glucose were observed.Conclusions
Although IL-1β inhibition with canakinumab had similar effects on major cardiovascular events among those with and without diabetes, treatment over a median period of 3.7 years did not reduce incident diabetes. (Canakinumab Anti-inflammatory Thrombosis Outcomes Study [CANTOS]; NCT01327846) 相似文献30.
Partha Dutta Friedrich Felix Hoyer Lubov S. Grigoryeva Hendrik B. Sager Florian Leuschner Gabriel Courties Anna Borodovsky Tatiana Novobrantseva Vera M. Ruda Kevin Fitzgerald Yoshiko Iwamoto Gregory Wojtkiewicz Yuan Sun Nicolas Da Silva Peter Libby Daniel G. Anderson Filip K. Swirski Ralph Weissleder Matthias Nahrendorf 《The Journal of experimental medicine》2015,212(4):497-512
Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)+ macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE−/− mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques.Leukocytosis correlates closely with cardiovascular mortality. In the steady state, blood leukocytes derive exclusively from bone marrow hematopoietic stem cells (HSCs). Supporting cells (Sugiyama et al., 2006; Ding et al., 2012; Ding and Morrison, 2013), including macrophages (Winkler et al., 2010; Chow et al., 2011), maintain the bone marrow HSC niche and regulate hematopoietic stem and progenitor cell (HSPC) activity by supplying various cytokines and retention factors. Systemic inflammation can stimulate extramedullary hematopoiesis in adult mice and humans. Splenic myelopoiesis supplies inflammatory monocytes to atherosclerotic plaques (Robbins et al., 2012) and the ischemic myocardium (Leuschner et al., 2012). In ischemic heart disease, HSPCs emigrate from the bone marrow, seed the spleen, and amplify leukocyte production (Dutta et al., 2012). Splenic HSPCs localize in the red pulp near the sinusoids in parafollicular areas (Kiel et al., 2005). Likewise, after adoptive transfer of GFP+ HSPCs, GFP+ colonies populate the splenic red pulp of atherosclerotic ApoE−/− mice (Robbins et al., 2012). During myocardial infarction (MI), proinflammatory monocytes derived from the spleen accelerate atherosclerotic progression (Dutta et al., 2012). Collectively, these data suggest that splenic myelopoiesis has promise as a therapeutic target; however, the components of the splenic hematopoietic niche are incompletely understood, especially compared with the well-studied bone marrow niche. Understanding HSC retention factors and their regulation in the spleen was the purpose of this study.Because the spleen harbors very few HSCs in the steady state, we investigated the splenic hematopoietic niche after injecting the Toll-like receptor ligand LPS to activate extramedullary hematopoiesis. In the bone marrow, macrophages are an integral part of the HSC niche (Winkler et al., 2010; Chow et al., 2011) and differentiation depends on the receptor for macrophage colony-stimulating factor (M-CSFR, CD115; Auffray et al., 2009). We thus hypothesized that splenic hematopoietic niche assembly also requires M-CSFR signaling. In line with knockout studies (Takahashi et al., 1994; Dai et al., 2002), in vivo knockdown of M-CSFR with nanoparticle-encapsulated siRNA reduced splenic macrophage numbers substantially. Interestingly, decreased macrophage numbers were associated with a reduction of splenic HSCs. Depleting macrophages with diphtheria toxin (DT) in CD169 iDTR mice reproduced the findings obtained with M-CSF–directed siRNA treatment, thereby indicating that macrophages have a key role in splenic HSC maintenance. To investigate how splenic macrophages retain HSCs, we measured changes in splenic expression of major bone marrow retention factors after M-CSFR silencing. Silencing M-CSFR selectively reduced splenic VCAM-1, and the adhesion molecule was primarily expressed by macrophages. Inhibiting macrophage expression of VCAM-1 with siRNA targeting this adhesion molecule reduced splenic HSPC numbers. Finally, we found that M-CSFR and macrophage-directed VCAM-1 silencing in mice with atherosclerosis mitigated blood leukocytosis and dampened inflammation in atherosclerotic plaques and the infarcted myocardium. These data reveal the importance of VCAM-1 expression by splenic macrophages for extramedullary hematopoiesis and illustrate the therapeutic potential of RNAi as an antiinflammatory that mutes emergency overproduction and provision of myeloid cells. 相似文献