tbuckley/cabot-search huggingface dataset:
Parenting: a genetic-epidemiologic perspective
Authors: K S Kendler
Journal: American Journal of Psychiatry (1996)

To understand the relation between parenting and later psychopathology, it is important to clarify the role of genetic and environmental factors in both the elicitation and the provision of parenting behavior.A 16-item version of the Parental Bonding Instrument was administered to 1) 606 fathers and 848 mothers of an epidemiologic sample of adult female-female twin pairs, who reported on their parenting of their twins; 2) the twins (both members of 546 monozygotic and 390 dizygotic pairs), who reported on the parenting they had received from their father and mother; 3) co-twins from these pairs, who reported on the parenting provided by their father and mother to their twin sister; and 4) members of the adult twin pairs (145 monozygotic and 117 dizygotic) who both had children, who reported on the parenting they provided to their offspring. The data were subjected to model fitting decomposing three sources of variance: additive genetic factors; family, or common, environment; and an individual's unique environment.Responses to the Parental Bonding Instrument produced three factors: parental warmth, protectiveness, and authoritarianism. According to parents, these factors were largely a common environmental experience for their children. Responses from twins, however, indicated that genetic factors played a substantial role in the elicitation of warmth from parents and a more modest role in influencing parental protectiveness and authoritarianism. While reports of twins and co-twins on protectiveness and authoritarianism yielded similar results, analysis of responses from co-twins indicated a degree of importance of genetic factors in eliciting parental warmth which was midway between that from parents' reports and twins' reports. Answers from twins as parents indicated that provision of warmth was substantially heritable, while resemblance between twins in providing protectiveness and authoritarianism was due to family environment.The provision of parenting is influenced by attitudes derived from the parent's family of origin as well as by genetically influenced parental temperamental characteristics. The elicitation of parenting is influenced by temperamental traits of the offspring that are, in turn, under partial genetic control. Genetic factors in both parent and child are more important for warmth than for protectiveness or authoritarianism.
Patient access to records: tonic or toxin?
Authors: L H Roth, J Wolford, A Meisel
Journal: American Journal of Psychiatry (1980)

The authors review their experiences in permitting psychiatric patients to read their own records. Patients are permitted to read the records with a staff member present to explain the information in the record. Copies of the records are not provided, nor is the patient always provided access to the complete record. Permitting this type of limited patient access to records has resulted in a generally positive experience for the patients, and harm has not ensued.
Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications
Authors: Wenhui Li, Stephan Urban
Journal: Journal of Hepatology (2016)

For almost three decades following the discovery of the human Hepatitis B Virus (HBV) the early events of virus infection (attachment to hepatocytes, specific binding to a receptor on hepatocytes) remained enigmatic. The gradual improvement of tissue culture systems for HBV has enabled the identification of viral determinants for viral infectivity and facilitated the discovery of the human sodium taurocholate co-transporting polypeptide (hNTCP) as a liver specific receptor of HBV and its satellite, the human Hepatitis Delta Virus (HDV). These findings are currently leading basic and clinical research activities in new directions. (1) Stable hNTCP-expressing cell lines have become a valuable platform to study the full HBV replication cycle from its native template, the cccDNA. (2) The suitability of NTCP complemented cell culture systems for high throughput screening approaches will facilitate identification of novel host factors involved in HBV replication (including those that determine the peculiar host specificity of HBV infection) and will enable identification and development of novel drug candidates for improved therapeutics. (3) Since NTCP is a major host-specific restriction factor for HBV and HDV, hNTCP-expressing animals provide the basis for future susceptible in vivo models. (4) The concept obtained with the entry inhibitor Myrcludex B demonstrates that NTCP is a suitable target for clinical interference with viral entry. This will foster further clinical approaches aiming at curative combination therapies.
Peripheral Embolism from an Aortic-Arch Atheroma
Authors: James Sangyop Lee, P A N Chandraratna
Journal: New England Journal of Medicine (2003)

A 62-year-old man presented with a one-month history of pain in the toes of both feet and in the left fourth fingertip. Examination revealed gangrene of the fingertip and all five toes of the right foot (Panel A), as well as dry gangrene of the fourth and fifth toes of the left foot. He had palpable bilateral femoral, popliteal, posterior tibial, and radial pulses and a diminished dorsalis pedis pulse. An angiogram of the legs and feet revealed occlusion of both anterior tibial arteries. A transesophageal echocardiogram (Panel B) revealed an ulcerated plaque (PL) in the aortic arch (Ao), with . . .
Arteriographic Assessment of Lung Scanning in the Diagnosis of Pulmonary Thromboembolism
Authors: Herbert L. Fred, John A. Burdine, David A. Gonzalez, Robert W. Lockhart, Carroll A. Peabody, James K. Alexander
Journal: New England Journal of Medicine (1966)

SCINTILLATION scanning of the lungs is being used with increasing frequency as a means of establishing the diagnosis of pulmonary thromboembolism.1 2 3 4 5 6 Little information is available, however, concerning the reliability and specificity of the technic in reflecting the presence and extent of intra-arterial lesions. Since arteriography of the lung permits identification of structural changes within the pulmonary arteries7 8 9 10 11 12 13 it serves as a way of assessing the accuracy of the scan in the diagnosis of thromboembolic disease. Therefore, we performed selective pulmonary arteriography and radioisotopic lung scans in patients suspected of having pulmonary thromboembolism and in patients known to have other cardiorespiratory . . .
Radioimmunoassay of the Attack Complex of Complement in Serum from Patients with Systemic Lupus Erythematosus
Authors: Ronald J. Falk, Agustin P. Dalmasso, Youngki Kim, Sylvia Lam, Alfred Michael
Journal: New England Journal of Medicine (1985)

We developed a radioimmunoassay to measure the attack complex of complement (SC5b–9) in serum from patients with systemic lupus erythematosus. The radioimmunoassay used a monoclonal antibody to an antigen of C9, which is absent from native C9 but present on SC5b–9. SC5b–9 was detectable in 13 of 63 normal subjects, with a mean value of 0.5 unit (range, 0 to 4.8), and elevated in 13 of 14 patients with active lupus. Analysis of 108 samples from the patients with lupus revealed a mean value of 10.1 units (range, 0 to 35) when the disease was active and 1.0 unit (range, 0 to 4.3) when it was clinically stable. SC5b–9 was a more sensitive measure of disease activity than C3, C4, or CH50; its specificity was equivalent to that of C3 and C4. SC5b–9 was elevated in serum from 6 of 49 patients with other forms of glomerulonephritis. Our study documents the presence of SC5b–9 in abnormal serum and correlates its elevation with clinical disease activity in patients with active systemic lupus erythematosus. (N Engl J Med 1985; 312:1594–9.)
Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice
Authors: Yu Feng, Jijing Tian, Heidi Qunhui Xie, Jianwen She, Sherry Li Xu, Tuan Xu, Wenjing Tian, Hualing Fu, Shuaizhang Li, Wuqun Tao, Lingyun Wang, Yangsheng Chen, Songyan Zhang, Wanglong Zhang, Tai L. Guo, Bin Zhao
Journal: Environmental Health Perspectives (2016)

Background:Although the chlorinated flame retardant Dechlorane (Dec) 602 has been detected in food, human blood, and breast milk, there is limited information on potential health effects, including possible immunotoxicity.Objectives:We determined the immunotoxic potential of Dec 602 in mice by examining the expression of phenotypic markers on thymocyte and splenic lymphocyte subsets, Th1/Th2 transcription factors, and the production of cytokines and antibodies.Methods:Adult male C57BL/6 mice were orally exposed to environmentally relevant doses of Dec 602 (1 and 10 μg/kg body weight per day) for 7 consecutive days. Thymocyte and splenic CD4 and CD8 subsets and splenocyte apoptosis were examined by flow cytometric analysis. Cytokine expression was measured at both the mRNA and the protein levels. Levels of the transcription factors Th1 (T-bet and STAT1) and Th2 (GATA3) were determined using quantitative real-time polymerase chain reaction (qPCR). Serum levels of immunoglobulins IgG1, IgG2a, IgG2b and IgE were measured by enzyme-linked immunosorbent assay (ELISA).Results:Splenic CD4+ and CD8+ T cell subsets were decreased compared with vehicle controls, and apoptosis was significantly increased in splenic CD4+ T cells. Expression (mRNA and protein) of Th2 cytokines [interleukin (IL)-4, IL-10, and IL-13] increased, and that of Th1 cytokines [IL-2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] decreased. The Th2 transcriptional factor GATA3 increased, whereas the Th1 transcriptional factors T-bet and STAT1 decreased. As additional indicators of the Th2-Th1 imbalance, production of IgG1 was significantly increased, whereas IgG2a was reduced.Conclusions:To our knowledge, we are the first to report evidence of the effects of Dec 602 on immune function in mice, with findings indicating that Dec 602 exposure favored Th2 responses and reduced Th1 function.Citation:Feng Y, Tian J, Xie HQ, She J, Xu SL, Xu T, Tian W, Fu H, Li S, Tao W, Wang L, Chen Y, Zhang S, Zhang W, Guo TL, Zhao B. 2016. Effects of acute low-dose exposure to the chlorinated flame retardant dechlorane 602 and Th1 and Th2 immune responses in adult male mice. Environ Health Perspect 124:1406–1413; http://dx.doi.org/10.1289/ehp.1510314
Oxaliplatin, 5-fluorouracil, and leuvocorin and (FOLFOX-4) combination chemotherapy as salvage treatment in pretreated patients with advanced gastric cancer (AGC)
Authors: Y. Kim, S. Park, J. Park, E. Cho, D. Shin, J. Lee
Journal: Journal of Clinical Oncology (2008)

4577 Background: FOLFOX-4 combination chemotherapy has demonstrated activity against AGC. This study was designed to determine the effectiveness and tolerance of the FOLFOX-4 when used as a salvage treatment in patients with AGC who failed after prior fluoropyrimidine and platinum-containing regimens. Methods: AGC patients with an ECOG performance status of 0–1, progressive after prior treatments with both fluoropyrimidine and platinum, were registered onto this trial. Oxaliplatin was administered on day 1 at the dose of 85 mg/m2 as a 2-hour infusion, concurrently with leucovorin 200 mg/m2/day, followed by bolus 5-fluorouracil (FU) 400 mg/m2 and a 22-hour infusion of FU 600 mg/m2 for 2 consecutive days. The treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred, or until a patient chose to discontinue treatment. Results: In a total of 42 patients registered, all were previously treated either with a FU and cisplatin combination, or with a cisplatin-based regimen followed by second-line chemotherapy containing fluoropyrimidines. A total of 217 chemotherapy cycles were delivered (median 4, range 1–18). The patients' median age was 57 years (range 32–75) and 32 (76%) had tumor-related symptoms (performance status of 1). Eight patients (19%) achieved an objective response (1 CR, 7 PRs) which maintained for a median of 3 months. Thirteen additional patients achieved stable disease. The median progression-free survival was 3.9 months (95% CI 2.2–5.6) and the overall survival was 5.8 months (95% CI 5.0–6.6). Major toxic effects included nausea, diarrhea and peripheral neuropathy. Although there was one possible treatment-related death, toxicity profiles were generally predictable and manageable. Conclusions: Salvage chemotherapy with FOLFOX-4 is an active and well tolerated regimen for heavily pretreated patients with AGC. No significant financial relationships to disclose.
Case 10-1979
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, David M. Dawson, Edward P. Richardson, Robert B. Colvin
Journal: New England Journal of Medicine (1979)

Presentation of CaseA 31-year-old woman, a Mexican national, was admitted to the hospital because of weakness of the hands.She was well until five years earlier, when she burned her right hand but experienced no pain. Numbness appeared in the hands several weeks later and subsequently in the feet. She entered a hospital in Mexico, where a cervical pneumomyelographic study was reported to be negative. A diagnosis of avitaminosis was made, and a multiple-vitamin preparation was administered for six months, without improvement. The areas of numbness spread to the midportions of the shins and the brachial regions, with frequent . . .
Abstract POSTER-THER-1418: PD-1 mediated paralysis of ovarian cancer infiltrating dendritic cells
Authors: Lavakumar Karyampudi, James Krempski, Purushottam Lamichhane, Kimberly R. Kalli, Marshall D. Behrens, Doris M. Vargas, Lynn C Hartmann, Karen E Hedin, Ellen L. Goode, Keith L. Knutson
Journal: Clinical Cancer Research (2015)

Abstract Purpose: It is well known that the immune system impacts the clinical course of ovarian cancer suggesting that immune-based approaches may effective in treating the disease. This has led to several clinical trials of novel treatments such as antibody, vaccine, and adoptive T cell therapy. PD-1:PD-L1 axis is a major immune regulatory pathway that blunts immune effectors in the tumor microenvironment. It is well known that high surface expression of PD-1 on tumor infiltrating T cells is a sign of their exhaustion. However, the complete mechanism behind the PD-1 regulation of T cell exhaustion is yet to be explored. Recently we identified that PD-1 is also expressed on ovarian tumor-infiltrating myeloid dendritic cells (DCs) that exhibit an immunosuppressive phenotype. Our goal in this study was to understand the mechanism by which PD-1 mediates the paralysis of ovarian cancer infiltrating DCs. Experimental procedures: PD-1+ DCs obtained from ID8 mouse model of ovarian cancer were used in this study. Data from this preclinical model was confirmed by using myeloid DCs obtained from ovarian cancer patient’s samples. Using standard flow cytometry, immunoassays (ELISA, multiplexed cytokine assay), PCR array, western blot and confocal microscopy, PD-1 mediated paralysis of ovarian cancer DCs was determined. Results: Our data shows that blockade of surface PD-1 on ovarian cancer infiltrating DCs results in their activation by, enhancing their surface co-stimulatory molecules expression, increasing their motility, enhancing their antigen presentation capacity, and increasing their production of immunostimulatory cytokines. Also, our results suggest that PD-1 expressed on tumor DCs mediates the suppression of NFkB which occurs through SHP-2 and IKK dependent mechanisms. Conclusion: Our study reveals that blockade of PD-1 on ovarian cancer infiltrating DCs results in the reversal of their paralysis to such an extent that it overrides their B7-H1 mediated suppression of T cells and this occurs through the reversal of PD-1 mediated tonic suppression of NFkB. Citation Format: Lavakumar Karyampudi James Krempski, Purushottam Lamichhane, Kimberly R. Kalli, Marshall D. Behrens, Doris M. Vargas, Lynn C Hartmann, Karen E Hedin, Ellen L. Goode, Keith L. Knutson. PD-1 mediated paralysis of ovarian cancer infiltrating dendritic cells [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-THER-1418.
Outcome of patients (pts) with brain metastases (BMs) from HER2-positive breast cancer (BC) treated with lapatinib plus capecitabine (LC).
Authors: G. Metro, J. Foglietta, L. Stocchi, M. Russillo, P. Papaldo, L. Crino, D. Giannarelli, F. Cognetti, A. Fabi, S. Gori
Journal: Journal of Clinical Oncology (2010)

1155 Background: In the present analysis we investigated retrospectively the efficacy of LC for BMs from HER2+ BC. Secondly, we evaluated the clinical outcome of HER2+ BC pts with BMs treated with LC. Methods: Out of the 81 HER2+ metastatic BC pts treated with lapatinib (1,250 mg p.o. daily) plus capecitabine (2,000 mg/mq p.o. dd 1-14 every 21) at two Italian institutions, we identified 34 pts with evidence of BMs prior to the start of LC. Only pts naïve for both lapatinib and capecitabine were included, which left a total of 30 pts available for the analysis. In a second step, we compared the overall survival (OS) from the development of BMs of these 30 pts vs. a group of 23 pts who had received only trastuzumab-based therapies beyond brain progression. Results: The median age of the 30 LC-treated pts was 45 years (range 24-75). All of them had received prior treatment with a taxane, an anthracycline, and trastuzumab (median no. of trastuzumab-based therapies for metastatic BC=2). 26/30 pts had received prior radiotherapy for BMs. In 6/30 pts LC was delivered as first systemic treatment after the development of BMs, whereas in 24/30 pts it was administered following one trastuzumab-based therapy. In the 22 patients with BMs evaluable for response (one or more progressive BMs ≥ 1 cm; WBRT and/or SRS received ≥ 3 months prior to LC), 7 PR (32%) and 6 SD (27.5%) were observed with LC. The median duration of brain response was 6 months (range 3-25). The median brain progression-free survival was 5.6 months (95% CI, 4.4-6.8) and the percentages of pts without brain progression at 2, 4, and 6 months were 83.3%, 60%, and 45.9%, respectively. The median OS (from the start of LC) was 11 months (95% CI, 4.3-17.6). When comparing the OS (as assessed from the time of development of BMs) of these 30 pts with that of 23 pts treated only with trastumumab-based therapies beyond brain progression, a significantly higher OS was observed in favor of the LC-treated pts (27.8 months vs. 16.7 months, respectively; p=0.01). Conclusions: LC is active for established BMs from HER2+ BC in pts who are naïve for either lapatinib and capecitabine. Using LC after the development of BMs appears to improve OS vs. receiving only trastuzumab-based therapy. No significant financial relationships to disclose.
The Role of the Topical Anesthetic Agent in Modifying Bacteriologic Data Obtained by Bronchoscopy
Authors: Biagio A. Conte, Eugene G. Laforet
Journal: New England Journal of Medicine (1962)

ALTHOUGH various local and topical anesthetics have long been alleged to inhibit bacterial growth it is only recently that this has been critically investigated, at least in relation to bronchoscopy. A frequent major objective of diagnostic bronchoscopy is to obtain secretion for bacteriologic study. The potential role of the topical anesthetic agent in modifying the success of this undertaking, however, has not been sufficiently considered. It is the purpose of this paper to emphasize a recent study indicating that cultural growth of bacteria and fungi obtained bronchoscopically may be inhibited by the topical anesthetic employed,1 to extend this finding specifically . . .
Ineffectiveness of Ascorbic Acid Therapy in Nephropathic Cystinosis
Authors: Jerry A. Schneider, James J. Schlesselman, Stanley A. Mendoza, Sheldon Orloff, Jess G. Thoene, Wolfgang A. Kroll, Alfred D. Godfrey, Joseph D. Schulman
Journal: New England Journal of Medicine (1979)

Because high concentrations of ascorbic acid (0.57 mM) lower the free (nonprotein) cystine content of cultured cystinotic skin fibroblasts by over 50 per cent, we did a double-blind clinical trial to establish whether this drug would benefit cystinotic children. Sixty-four patients were randomized into the study; 32 received ascorbic acid (200 mg per kilogram of body weight per day), and 32 placebo. The study was terminated after approximately two years because there was no indication that vitamin C was beneficial and accumulating evidence that it might be harmful. Of 11 patients who left the study because of death or the requirement for dialysis or renal transplantation, eight were receiving ascorbic acid. The estimated relative risk (treatment vs. control) of an adverse event was R = 2.7, with a 90 per cent confidence interval of (0.8, 11.5). The serum creatinine concentration increased 0.53 mg per deciliter per year in patients receiving vitamin C and 0.24 mg per deciliter per year in patients receiving placebo (P = 0.08).
BMET-36TUMOR PROFILES OF BRAIN METASTASES FROM NSCLC, BREAST CANCER AND MELANOMA
Authors: Santosh Kesari, Joanne Xiu, Jethro Hu, Michael Salacz, David Piccioni, Sandeep Reddy
Journal: Neuro-Oncology (2015)

BMET-36. TUMOR PROFILES OF BRAIN METASTASES FROM NSCLC, BREAST CANCER AND MELANOMA Santosh Kesari1, Joanne Xiu2, Jethro Hu3, Michael Salacz4, David Piccioni1, and Sandeep Reddy2; University of California, San Diego, La Jolla, CA, USA; Caris Life Sciences, Phoenix, AZ, USA; Cedars-Sinai, Los Angeles, CA, USA; University of Kansas Medical Center, Overland Park, KS, USA BACKGROUND: Approximately 70,000 diagnoses of brain metastases (BM) occur annually in the U.S. Despite its prominence, the biology of BM remains poorly-understood. We compared tumor profiles of BM from NSCLC, breast cancer (BC) and melanoma (ML) to understand the biology and to identify differential treatment strategies. METHODS: Tumors were profiled using a multiplatform service (Caris Life Sciences, Phoenix, AZ), including sequencing (Sanger, NGS), protein expression (IHC) and amplification (ISH). RESULTS: 5391 NSCLC (293 BM, 5098 lung), 3595 BC (99 BM, 3496 breast) and 761 ML (101 BM, 660 skin) were included. BM mutations remain largely similar to primary tumors with no consistent changes between cancers. In contrast, when comparing BM to primary tumors, protein expression of TOP2A (NSCLC: 75% vs. 55%; BC: 75% vs. 50%; ML: 76% vs. 46%, all p , 0.01); TOPO1 (64% vs.55%, p 1⁄4 0.02; 78% vs. 50%, p , 0.01; 61% vs. 57%, p 1⁄4 ns), TS (35% vs. 22%, p , 0.01, 39% vs. 28%, p 1⁄4 0.04, 56% vs. 45%, p 1⁄4 ns) and EGFR amplification (36% vs. 28%, p 1⁄4 ns, 31% vs. 14%, p , 0.01; 50% vs. 6%, p , 0.01) were more prevalent in BM. Higher PD-1 (83% vs. 63%, p 1⁄4 0.01, 60% vs. 53%, p 1⁄4 ns, 100% vs. 75%, p 1⁄4 ns) expression on TIL was observed in BM; PD-L1 is higher in the BM of NSCLC and BC (22% vs. 16%, p 1⁄4 ns; 40% vs. 12%, p 1⁄4 ns), but not in ML (75% vs. 80%, p 1⁄4 ns). CONCLUSIONS: The mutational landscape is similar in BM of NSCLC, BC and ML compared to primary tumors, suggesting that primary tumor and BM would respond to similar therapeutic agents with the consideration of effective blood-brain-barrier-penetrant drugs. Immune-checkpoint inhibitors could be considered for BM treatment based on PD-1, PD-L1 expression frequencies. Small-molecule EGFR inhibitors could be considered due to increased EGFR amplification; increased TOP2A, TOPO1 expression prompts consideration of topoisomerase inhibitors like etoposide or irinotecan. Neuro-Oncology 17:v45–v54, 2015. doi:10.1093/neuonc/nov208.36 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.