tbuckley/cabot-search huggingface dataset:
Pneumatoceles and pneumothoraces complicating staphylococcal pneumonia: treatment by synchronous independent lung ventilation.
Authors: A W Lohse, O Klein, E Hermann, H Lohr, K F Kreitner, H Steppling, K H Meyer zum Buschenfelde, M Staritz
Journal: Thorax (1993)

A 54 year old man with a staphylococcal sepsis developed staphylococcal pneumonia complicated by multiple pneumatoceles and bilateral tension pneumothoraces caused by bronchopleural fistulae. Excessive enlargement of the right sided pneumatoceles and a tension pneumothorax not improved by drainage led to mediastinal shift and compression of the right lung. Reversal of the mediastinal shift and closure of the bronchopleural fistulae was achieved by assisted independent lung ventilation.
Primary Dietary Intervention Study to Reduce the Risk of Islet Autoimmunity in Children at Increased Risk for Type 1 Diabetes
Authors: Sandra Hummel, Maren Pflüger, Michael Hummel, Ezio Bonifacio, Anette-G. Ziegler
Journal: Diabetes Care (2011)

OBJECTIVE To determine whether delaying the introduction of gluten in infants with a genetic risk of islet autoimmunity is feasible, safe, and may reduce the risk of type 1 diabetes–associated islet autoimmunity. RESEARCH DESIGN AND METHODS A total of 150 infants with a first-degree family history of type 1 diabetes and a risk HLA genotype were randomly assigned to a first gluten exposure at age 6 months (control group) or 12 months (late-exposure group) and were followed 3 monthly until the age of 3 years and yearly thereafter for safety (for growth and autoantibodies to transglutaminase C [TGCAs]), islet autoantibodies to insulin, GAD, insulinoma-associated protein 2, and type 1 diabetes. RESULTS Adherence to the dietary-intervention protocol was reported from 70% of families. During the first 3 years, weight and height were similar in children in the control and late-exposure groups, as was the probability of developing TGCAs (14 vs. 4%; P = 0.1). Eleven children in the control group and 13 children in the late-exposure group developed islet autoantibodies (3-year risk: 12 vs. 13%; P = 0.6). Seven children developed diabetes, including four in the late-exposure group. No significant differences were observed when children were analyzed as per protocol on the basis of the reported first gluten exposure of the children. CONCLUSIONS Delaying gluten exposure until the age of 12 months is safe but does not substantially reduce the risk for islet autoimmunity in genetically at-risk children.
Demographic Information for Patients with Eosinophilic Esophagitis
Authors: M.L. Heltzer, J.P. Franciosi, M. Shuker, C.A. Liacouras, J.M. Spergel
Journal: Journal of Allergy and Clinical Immunology (2007)

RATIONALE: African Americans have a higher prevalence of asthma and are known to introduce solid foods earlier than European Americans, which might play a role in risk for early atopic dermatitis (AD) and wheeze.We explored, by race, the relationship of early (<3 months) introduction of solid foods to incidence of AD and wheeze by 6 months, and infant IgE, using a diverse birth cohort known as WHEALS.METHODS: To date, of 724 infant with cord blood samples, 260 infants have 6-month interview data and IgE measures (always presented as geometric means) and 164 have follow up at 12 months.AD/wheeze was defined as mother's report of physician-diagnosed eczema rash/wheeze.RESULTS: Mean age of cohort mothers was 29.4 years; 53% were African-American.Incidence of 6-month AD and wheeze, and 1-year wheeze, was 2.7%, 6.2%, and 8.0%, respectively, with no race differences.Early solid food, reported by 20.9% of African-Americans vs. 7.5% of European-Americans (p50.01), was a strong predictor of 6-month AD in African-Americans, relative risk (95% confidence interval)55.7(1.0-33.2),p50.05; but not in European-Americans, RR51.4(0.2-10.1),p50.77.The 6-month IgE was higher for European-Americans with AD than those without (IgE575.0vs. 6.3, p50.003); but less so for African-Americans (IgE515.8 vs. 8.0, p50.42).Having AD at 6-months increased risk of 1-year wheeze among African-Americans more so than for European-Americans (RR58.3(3.2-21.9),p<0.01 vs. 3.0(0.8-11.1),p50.10).Trends are sustained after adjusting for infant birthweight.CONCLUSIONS: Race modifies the associations of early solid foods to AD and of AD to prevalent/incident wheeze.Involvement of IgE may also differ by race.
CHANGES IN BLOOD PRESSURE WITH ELECTROSHOCK THERAPY IN A PATIENT RECEIVING CHLORPROMAZINE HYDROCHLORIDE (THORAZINE)
Authors: DANIEL M. WEISS
Journal: American Journal of Psychiatry (1955)

A case is presented which did not respond to the administration of chlorpromazine hydrochloride in the level of 450 mgm daily, but instead seemed to become more regressed and hyperactive. Electroshock therapy was given as a lifesaving measure while the patient was still receiving chlorpromazine hydrochloride in large doses. A marked fall in blood pressure occurred immediately following the treatment, and a return to the baseline level was seen within 30 minutes. The degree of drop in blood pressure was greater when larger doses of the drug had been received by the patient. This fall in pressure was not present in subsequent treatments, when the patient was not receiving chlorpromazine hydrochloride. It is felt therefore that the hypotensive action of chlorpromazine hydrochloride is intensified by electroshock therapy. Careful search of the literature has not disclosed a similar case.
Identification of unfavourable paired cell interactions in follicular lymphoma using hypothesized interaction distribution (HID) analysis
Authors: James Mansfield, Lilli Nelson, Kim Linton, Chris Rose, Richard Byers
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Histopathological prognostication relies on pattern recognition, but as the number of biomarkers increases, human prognostic pattern recognition ability decreases. We have developed an automated quantitative method, hypothesized interaction distribution (HID) analysis, for
DISCOVERING THE ORIGINS OF IMMUNOLOGICAL COMPETENCE
Authors: Jacques F. A. P. Miller
Journal: Annual Review of Immunology (1999)

[Figure: see text] ▪ Abstract Work done in the late 1950s and in the 1960s revealed the role of the thymus in virus-induced leukemia in mice. Thymectomizing mice at birth to test whether the virus first multiplied in thymus tissue and then spread elsewhere ultimately led to the conclusion that the thymus was essential to the normal development of the immune system. Subsequent testing to try to understand how the thymus contributes to the pool of immunocompetent lymphocytes opened a new chapter in immunology and required a reappraisal of many immunological phenomena and an understanding of the molecular interactions that take place during cell-to-cell interactions.
Cost Sharing and Adherence to Tyrosine Kinase Inhibitors for Patients With Chronic Myeloid Leukemia
Authors: Stacie B. Dusetzina, Aaron N. Winn, Gregory A. Abel, Haiden A. Huskamp, Nancy L. Keating
Journal: Journal of Clinical Oncology (2013)

The introduction of imatinib, a tyrosine kinase inhibitor (TKI), has greatly increased survival for patients with chronic myeloid leukemia (CML). Conversely, nonadherence to imatinib and other TKIs undoubtedly results in disease progression and treatment resistance. We examined trends in imatinib expenditures from 2002 to 2011 and assessed the association between copayment requirements for imatinib and TKI adherence.We used MarketScan health plan claims from 2002 to 2011 to identify adults (age 18 to 64 years) with CML who initiated imatinib therapy between January 1, 2002, and June 30, 2011, and had insurance coverage for at least 3 months before through 6 months after initiation (N = 1,541). Primary outcomes were TKI discontinuation and nonadherence. The primary independent variable was out-of-pocket cost for a 30-day supply of imatinib. By using a propensity-score weighted sample, we estimated the risk of discontinuation and nonadherence for patients with higher (top quartile) versus lower copayments.Monthly copayments for imatinib averaged $108; median copayments were $30 (range, $0 to $4,792). Mean total monthly expenditures for imatinib nearly doubled between 2002 and 2011, from $2,798 to $4,892. Approximately 17% of patients with higher copayments and 10% with lower copayments discontinued TKIs during the first 180 days following initiation (adjusted risk ratio [aRR], 1.70; 95% CI, 1.30 to 2.22). Similarly, patients with higher copayments were 42% more likely to be nonadherent (aRR, 1.42; 95% CI, 1.19 to 1.69).Patients with higher copayments are more likely to discontinue or be nonadherent to TKIs. Given the importance of these therapies for patients with CML, our data suggest a critical need to reduce patient costs for these therapies.
Role of Caspases in Hypoxia-Induced Necrosis of Rat Renal Proximal Tubules
Authors: CHARLES L. EDELSTEIN, YUEXIAN SHI, ROBERT W. SCHRIER
Journal: Journal of the American Society of Nephrology (1999)

The role of the caspases, a newly discovered group of cysteine proteases, was investigated in a model of hypoxia-induced necrotic injury of rat renal proximal tubules. An assay for caspases in freshly isolated rat proximal tubules was developed. There was a 40% increase in tubular caspase activity after 15 min of hypoxia in association with increased cell membrane damage as indicated by a threefold increase in lactate dehydrogenase release. The specific caspase inhibitor Z-Asp-2,6-dichlorobenzoyloxymethylketone (Z-D-DCB) attenuated the increase in caspase activity during 15 min of hypoxia and markedly decreased lactate dehydrogenase release in a dose-dependent manner. In the proximal tubules, Z-D-DCB also inhibited the hypoxia-induced increase in calpain activity, another cysteine protease. In contrast, when Z-D-DCB was added to purified calpain in vitro, there was no inhibition of calpain activity. The calpain inhibitor (2)-3-(4-iodophenyl)-2-mercapto-2-propenoic acid (PD150606) also inhibited the hypoxia-induced increase in caspase activity in proximal tubules, but did not inhibit the activity of purified caspase 1 in vitro. In these experiments, caspase activity was detected with the fluorescence substrate Ac-Tyr-Val-Ala-Asp-7-amido-4-methyl coumarin (Ac-YVAD-AMC), which is preferentially cleaved by caspase 1. However, minimal caspase activity was detected with the fluorescence substrate Ac-Asp-Glu-Val-Asp-7-amido-4-methyl coumarin (Ac-DEVD-AMC), which is cleaved by caspases 2, 3, and 7. The present study in proximal tubules demonstrates that (1) caspase inhibition protects against necrotic injury by inhibition of hypoxia-induced caspase activity; and (2) caspase 1 may be the caspase involved. Thus, although the role of caspases in apoptotic cell death is well established, this study provides new evidence that caspases contribute to necrotic cell death as well.
Association of Angiotensin-Converting Enzyme With Low-Density Lipoprotein in Aortic Valvular Lesions and in Human Plasma
Authors: Kevin D. O’Brien, David M. Shavelle, Michael T. Caulfield, Thomas O. McDonald, Katherine Olin-Lewis, Catherine M. Otto, Jeffrey L. Probstfield
Journal: Circulation (2002)

Background— Recent studies have demonstrated that lesions of aortic sclerosis and stenosis share several similarities with lesions of atherosclerosis. In atherosclerosis, angiotensin-converting enzyme (ACE) is expressed by a subset of macrophages. This study was undertaken to determine whether ACE might be present in aortic sclerosis or stenosis lesions. Methods and Results— Immunohistochemistry was performed on 26 paraffin-embedded human aortic valves. Monospecific antibodies were used to identify ACE, macrophages, angiotensin II type 1 receptor (AT-1 receptor), angiotensin II, and apolipoprotein B. Human low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were isolated from plasma of normal volunteers by sequential density-gradient ultracentrifugation. ACE was not present in normal valves but was present in all valves with aortic sclerosis or stenosis lesions. ACE was detected on a subset of lesion macrophages but was present primarily in an extracellular distribution, where it colocalized with apolipoprotein B. ACE was detected by Western blotting on plasma LDL but not on HDL isolated from normal volunteers. Angiotensin II, the enzymatic product of ACE, was colocalized with ACE in valve lesions. ACE also was colocalized with apolipoprotein B in an adjacent coronary atherosclerotic plaque. Conclusions— ACE is present in aortic sclerosis and stenosis lesions, where it may participate in lesion development, as is evidenced by the presence of its enzymatic product, angiotensin II. The observation of an association of ACE with LDL in both lesions and plasma suggests that LDL may deliver ACE to lesions and has implications for the role of ACE-containing LDL in other diseases, such as atherosclerosis.
Associations of Parental, Birth, and Early Life Characteristics With Systolic Blood Pressure at 5 Years of Age
Authors: Debbie A. Lawlor, Jake M. Najman, Jonathan Sterne, Gail M. Williams, Shah Ebrahim, George Davey Smith
Journal: Circulation (2004)

Background— We examined the associations of a range of parental and early life characteristics with systolic blood pressure at 5 years of age. Methods and Results— Information from 3864 children who were followed up prospectively from their mother’s first antenatal clinic assessment was used. Maternal age, body mass index, and smoking during pregnancy were all positively associated with offspring systolic blood pressure at 5 years of age. The systolic blood pressure of children whose mothers had smoked throughout pregnancy was on average 0.92 mm Hg (95% CI 0.17 to 1.68) greater than that of children whose mothers had never smoked, after full adjustment. Children who had been breast fed until at least 6 months had lower systolic blood pressure than those who were breast fed for a shorter duration. Paternal body mass index and child’s weight, height, and body mass index were all positively associated with blood pressure at age 5. Conclusions— Because childhood blood pressure tracks into adulthood, interventions aimed at early life risk factors, such as quitting smoking during pregnancy, breast feeding, and prevention of obesity in all family members, may be important for reducing the population distribution of blood pressure and thus cardiovascular disease risk.
Estrogen Receptor, Progesterone Receptor, HER-2, and Response to Postmastectomy Radiotherapy in High-Risk Breast Cancer: The Danish Breast Cancer Cooperative Group
Authors: Marianne Kyndi, Flemming B. Sørensen, Helle Knudsen, Marie Overgaard, Hanne Melgaard Nielsen, Jens Overgaard
Journal: Journal of Clinical Oncology (2008)

To examine the importance of estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER-2), and constructed subtypes in a large study randomly assigning patients to receive or not receive postmastectomy radiotherapy (PMRT).The present analysis included 1,000 of the 3,083 high-risk breast cancer patients randomly assigned to PMRT in the Danish Breast Cancer Cooperative Group (DBCG) protocol 82 trials b and c. Tissue microarray sections were stained for ER, PgR, and HER-2. Median follow-up time for patients alive was 17 years. End points were locoregional recurrence as isolated first event, distant metastases, and overall survival. For statistical analyses four subgroups were constructed from hormonal receptors (Rec). Rec+ was defined as ER+ and/or PgR+. Rec-as both ER-and PgR-. The four subgroups were Rec+/HER-2-, Rec+/HER-2+, Rec-/HER-2-(triple negative), and Rec-/HER-2+.A significantly improved overall survival after PMRT was seen only among patients characterized by good prognostic markers such as hormonal receptor-positive and HER-2- patients (including the two Rec+ subtypes). No significant overall survival improvement after PMRT was found among patients with an a priori poor prognosis, the hormonal receptor-negative and HER-2+ patients, and in particular the Rec-/HER-2+ subtype. Furthermore, comparing hazard ratios and 95% CIs, significantly smaller improvements in locoregional recurrence control after PMRT were found for ER-and PgR-tumors compared with the ER+ and PgR+ tumors (P = .003 and .04, respectively), and for the triple-negative (P = .02), and the Rec-/HER-2+ subtypes (P = .003) compared with the Rec+/HER-2-subtype.Hormonal receptor status, HER-2, and the constructed subtypes may be predictive of locoregional recurrence and survival after postmastectomy radiotherapy.
1007-172 Effect of fosinopril on cardiovascular events in relation to the intima-media thickness in microalbuminuric patients without hypertension
Authors: Folkert W Asselbergs, Christiane A Geluk, Arie M van Roon, Paul E de Jong, Reinhold O.B Gans, Dirk J van Veldhuisen, Wiek H van Glist
Journal: Journal of the American College of Cardiology (2004)
Carcinogenicity of Tobacco and Tobacco Smoke
Authors: H. D. Beckett
Journal: BMJ (1967)

<h3>Introduction/Background*</h3> New/emerging therapies based on microsatellite instability (MSI) prognostic biomarker are altering the treatment landscape for advanced endometrial cancer (aEC). The real-world outcomes in aEC patients with MSI-high/deficient mismatch repair (MSI-H/dMMR) tumor status is not well understood. <h3>Methodology</h3> Endometrial Cancer Health Outcomes (ECHO) is a multicenter retrospective chart review study in women diagnosed with aEC in the US. Physicians extracted de-identified data from medical records of women (≥18 years-old) diagnosed with inoperable aEC, with known MSI/MMR status, who progressed after prior systemic therapy between 07/01/2016-07/30/2019. Data included patient demographics, clinical/treatment characteristics, and clinical outcomes. Kaplan-Meier analyses were performed to estimate time to treatment discontinuation, real-world progression-free survival (rwPFS) and overall survival (OS). The study was IRB approved. <h3>Result(s)*</h3> Among 130 MSI-H/dMMR aEC patients who progressed on a prior systemic therapy, mean age was 62 years, 57% had endometrioid carcinoma histology, and 93% had ECOG 0-1. As 2<sup>nd</sup>-line therapy, 79% of patients received immunotherapy (IO) ± chemotherapy (CT) (pembrolizumab monotherapy=71%), 14% received CT only, and 7% received hormonal or other therapy (HT/OT). Median duration of 2<sup>nd</sup> line therapy was 14 months. Median rwPFS from initiation of 2<sup>nd</sup>-line therapy was 17 months (95% confidence interval [CI]: 13-n/a) [IO±CT: 29 months (95% CI: 18-n/a); CT: 4 months (95% CI: 2-9)]. Median OS from 2<sup>nd</sup>-line therapy initiation was 30 months (95% CI: 18-n/a) [IO±CT: median not reached (95% CI: 30-n/a); CT: 5.5 months (95% CI: 4-n/a)]. (Table 1) <h3>Conclusion*</h3> In real-world practice, most MSI-high/dMMR aEC patients in the US who failed a prior systemic therapy, initiated immunotherapy with favorable outcomes.
Hematopoietic Stem Cells Contribute to the Regeneration of Renal Tubules after Renal Ischemia-Reperfusion Injury in Mice
Authors: Fangming Lin, Kimberly Cordes, Linheng Li, Leroy Hood, William G. Couser, Stuart J. Shankland, Peter Igarashi
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Ischemia-reperfusion injury (I/R injury) is a common cause of acute renal failure. Recovery from I/R injury requires renal tubular regeneration. Hematopoietic stem cells (HSC) have been shown to be capable of differentiating into hepatocytes, cardiac myocytes, gastrointestinal epithelial cells, and vascular endothelial cells during tissue repair. The current study tested the hypothesis that murine HSC can contribute to the regeneration of renal tubular epithelial cells after I/R injury. HSC isolated from male Rosa26 mice that express β-galactosidase constitutively were transplanted into female nontransgenic mice after unilateral renal I/R injury. Four weeks after HSC transplantation, β-galactosidase-positive cells were detected in renal tubules of the recipients by X-Gal staining. PCR analysis of the male-specific <i>Sry</i> gene and Y chromosome fluorescence <i>in situ</i> hybridization confirmed the presence of male-derived cells in the kidneys of female recipients. Antibody co-staining showed that β-galactosidase was primarily expressed in renal proximal tubules. This is the first report to show that HSC can differentiate into renal tubular cells after I/R injury. Because of their availability, HSC may be useful for cell replacement therapy of acute renal failure. E-mail: fangming.lin@UTSouthwestern.edu
Mitochondrial Genome of the Homoscleromorph Oscarella carmela (Porifera, Demospongiae) Reveals Unexpected Complexity in the Common Ancestor of Sponges and Other Animals
Authors: X. Wang, D. V. Lavrov
Journal: Molecular Biology and Evolution (2006)

Homoscleromorpha is a small group in the phylum Porifera (Sponges) characterized by several morphological features (basement membrane, acrosomes in spermatozoa, and cross-striated rootlets of the flagellar basal apparatus) shared with eumetazoan animals but not found in most other sponges. To clarify the phylogenetic position of this group, we determined and analyzed the complete mitochondrial DNA (mtDNA) sequence of the homoscleromorph sponge Oscarella carmela (Porifera, Demospongiae). O. carmela mtDNA is 20,327 bp and contains the largest complement of genes reported for animal mtDNA, including a putative gene for the C subunit of the twin-arginine translocase (tatC) that has never been found in animal mtDNA. The genes in O. carmela mtDNA are arranged in 2 clusters with opposite transcriptional orientations, a gene arrangement reminiscent of those in several cnidarian mtDNAs but unlike those reported in sponges. At the same time, phylogenetic analyses based on concatenated amino acid sequences from 12 mitochondrial (mt) protein genes strongly support the phylogenetic affinity between the Homoscleromorpha and other demosponges. Altogether, our data suggest that homoscleromorphs are demosponges that have retained ancestral features in both mt genome and morphological organization lost in other taxa and that the most recent common ancestor of sponges and other animals was morphologically and genetically more complex than previously thought.