tbuckley/cabot-search huggingface dataset:
Abstract 5309: Programmed Death Ligand-1 expression on the cell surface is regulated by Costimulatory Molecule CD80 expressed by cancer vaccines
Authors: Samuel T. Haile, Jacobus Bosch, Nnenna Agu, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2010)

Abstract With the lack of effective treatments for metastatic cancers, the employment of immunotherapies, cell-based vaccines particularly, to activate a patient's own immune system is a promising approach for the treatment of disseminated metastatic cancer. Many tumor cells constitutively express or are induced by Interferonγ (IFNγ) to express the inhibitory molecule Programmed Death Ligand 1 (PDL1). Since many cell-based vaccines are derived from tumor cells, the expression of PDL1 could reduce the therapeutic efficacy of the vaccines. PDL1 binds to its receptor Programmed Death 1 (PD1) on T cells and can signal for either apoptosis of T cells or can prevent their activation. As determined by flow cytometry using three anti-PDL1 monoclonal antibodies (mAb) that detect distinct PDL1 epitopes, and human lung, uveal melanoma, cutaneous melanoma, and breast cancer cells, the over-expression of CD80 blocks constitutive and IFNγ-induced cell surface expression of PDL1. Quantitative analysis of CD80 and PDL1 expression indicates an inverse relationship between PDL1 and CD80. CD80+ tumor cells contain intracellular PDL1, as assessed by flow cytometry, suggesting that CD80 regulates PDL1 at the protein level. Tumor cells transfected with CD80 constructs lacking a cytoplasmic domain or with an irrelevant non-signaling cytoplasmic domain, retain the ability to block PDL1 expression at the cell surface indicating that CD80 does not modulate PDL1 transcription via intracellular signaling. These results suggest that in addition to serving as a costimulatory molecule, CD80 facilitates T cell activation by blocking coinhibitory signals and preventing T cell apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5309.
Activation of Latent Infection by Indomethacin: a Report of Three Cases
Authors: L. Solomon
Journal: BMJ (1966)

ComncainBRITISH96 hepatocellular damage was seen in all six cases biopsied, but cholestasis was seen in only two of them.In this respect our findings are in conformity with the biochemical observations of Eisalo and of Palva and Mustala, in that abnormal enzyme levels are seen more frequently than abnormal biliary excretion tests.According to Eisalo et al. the biochemical changes of liver damage at contraceptive dose levels are transient, lasting only one to four weeks.The transaminase levels return to normal even when administration of the drug is continued.The recog- nition of these changes therefore requires repeated determina- tions in the first few weeks of drug administration-and this may be the reason for its failure to be recognized in some of the series mentioned at the beginning of this paper.However, at the higher dosage given in our series the raised transaminase levels continued throughout treatment.The presence of an alkylated group in the C17 position is the steroid configuration which is apt to induce hepatic damage and cholestasis when the drug is given in sufficient dosage for pro- longed periods (Sherlock, 1963).Both the progestogen and the oestrogen components of Lyndiol possess this configuration, and in our restricted series the combination of the two hormones caused considerably more liver damage than either alone.This is in conformity with Eisalo's findings.It has been suggested that there is synergic toxicity of the two components (Borglin, 1965).This is not proved, and the greater damage observed when they are combined may be purely an additive effect.At contraceptive dose levels Eisalo found a rise in transaminase levels from the progestogen component alone in only one out of 25 cases.At our dose level we found such changes in three out of seven cases, associated with parenchymal cell necrosis.Hepatotoxic changes following the administration of progestogens are probably therefore dose dependent.From Eisalo's reports (1964, 1965), it might be deduced also that for the same dose the hepatotoxic effect is greater in the post-menopausal than the pre-menopausal patient. SUMMARYA correlation has been established between raised serum glutamic oxalacetic transaminase levels and histological evidence of hepatocellular damage in a series of four postmenopausal patients treated by Lyndiol and seven patients treated by lynoestrenol, its progestogen component.Histological evidence of hepatocanalicular damage in a proportion of cases has also been demonstrated, but this does not appear to run parallel to changes in the transaminase levels.Raised enzyme levels persisted for many months when drug dosage at high levels was maintained.Mestranol, which is the oestrogen component of Lyndiol, caused no abnormality in biochemical liver tests in the four patients studied.The results suggest that the hepatotoxic effects of oral con- traceptives are mainly due to their progestogen content.
A comparison of diagnosis, evaluation, and treatment of patients with dermatologic disorders
Authors: Daniel Federman, Daniel Hogan, J.Richard Taylor, Panagiota Caralis, Robert S Kirsner
Journal: Journal of the American Academy of Dermatology (1995)

Background: Managed care in the American health care system may limit access to health care specialists. Objective: We assessed primary care providers' abilities at diagnosing and treating patients with a previously undiagnosed skin disorder. Methods: Patients with previously undiagnosed skin disorders were seen and examined sequentially by three groups of physicians: (1) internal medicine residents, (2) board-certified internal medicine attending physicians and (3) dermatology faculty. The internal medicine residents and attending physicians' diagnoses were compared with the dermatologists'. Appropriateness of therapy ordered by the internal medicine residents and attending physicians was assessed. Results: Medical residents' diagnoses were correct in 43% of the patients whereas the attending physicians diagnosed 52% of cases correctly. Attending physicians and residents frequently ordered therapy inappropriate for the patient's diagnosis. Internal medicine residents and attending physicians were more likely to order skin biopsies than dermatologists. Conclusion: Our results confirm earlier studies that nondermatologists perform poorly in the diagnosis and treatment of skin disease. Primary care providers should receive more training in dermatology, or dermatologists should be permitted to act as primary caregivers to patients with skin disease.
MONOZYGOTIC TWINS WITH OBSESSIONAL ILLNESS
Authors: ROBERT WOODRUFF, FERRIS N. PITTS
Journal: American Journal of Psychiatry (1964)

A pair of 17-year-old male, monozygotic twins concordant for obsessive illness is reported. Clinical evaluation of these twins is impressive in that their clinical course has been strikingly parallel. Both twins began to manifest compulsive mannerisms at about age 2½ and have continued to have some daily symptoms to the present time. Both entered a severe phase of illness in early adolescence; though both manifested all the characteristics of obsessional illness. Twin A was primarily occupied with ritual and Twin B with ruminative, anacastic, phobic thoughts. In each there was a marked diminution of symptoms at about age 14 following medical and psychiatric attention. Their mother has a mild unclassified neurotic illness without obsessive symptoms. The twin's father has a history of an erratic youth and there is a history of marked obsessive traits. The paternal grandmother manifested phobic and obsessive symptoms. Family and genetic studies from the literature on obsessive illness are reviewed.
Upper Airway Structure and Body Fat Composition in Obese Children with Obstructive Sleep Apnea Syndrome
Authors: Raanan Arens, Sanghun Sin, Kiran Nandalike, Jessica Rieder, Unab I. Khan, Katherine Freeman, Judith Wylie-Rosett, Michael L. Lipton, David M. Wootton, Joseph M. McDonough, Keivan Shifteh
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Mechanisms leading to obstructive sleep apnea syndrome (OSAS) in obese children are not well understood.Objectives: The aim of the study was to determine anatomical risk factors associated with OSAS in obese children as compared with obese control subjects without OSAS.Methods: Magnetic resonance imaging was used to determine the size of upper airway structure, and body fat composition. Paired analysis was used to compare between groups. Mixed effects regression models and conditional multiple logistic regression models were used to determine whether body mass index (BMI) Z-score was an effect modifier of each anatomic characteristic as it relates to OSAS.Measurements and Main Results: We studied 22 obese subjects with OSAS (12.5 ± 2.8 yr; BMI Z-score, 2.4 ± 0.4) and 22 obese control subjects (12.3 ± 2.9 yr; BMI Z-score, 2.3 ± 0.3). As compared with control subjects, subjects with OSAS had a smaller oropharynx (P < 0.05) and larger adenoid (P < 0.01), tonsils (P < 0.05), and retropharyngeal nodes (P < 0.05). The size of lymphoid tissues correlated with severity of OSAS whereas BMI Z-score did not have a modifier effect on these tissues. Subjects with OSAS demonstrated increased size of parapharyngeal fat pads (P < 0.05) and abdominal visceral fat (P < 0.05). The size of these tissues did not correlate with severity of OSAS and BMI Z-score did not have a modifier effect on these tissues.Conclusions: Upper airway lymphoid hypertrophy is significant in obese children with OSAS. The lack of correlation of lymphoid tissue size with obesity suggests that this hypertrophy is caused by other mechanisms. Although the parapharyngeal fat pads and abdominal visceral fat are larger in obese children with OSAS we could not find a direct association with severity of OSAS or with obesity.
(27) Focal dermal hypoplasia
Authors: R.H. Champion
Journal: British Journal of Dermatology (1975)

Journal Article (27) Focal dermal hypoplasia Get access R.H. Champion R.H. Champion Addenbrooke's Hospital, Cambridge Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 93, Issue s11, 1 July 1975, Pages 70–71, https://doi.org/10.1111/j.1365-2133.1975.tb06809.x Published: 01 July 1975
ChildLine report reveals extent of children's health fears
Authors: Z. Kmietowicz
Journal: BMJ (1998)

Children with a chronic illness, who are going through puberty, who wet the bed, or who have a sick parent feel depressed, miserable, worried, ashamed, and even suicidal, according to a review of callers to the free national telephone helpline, ChildLine.

The extent of the embarrassment, distress, and anxiety that children feel about their own or their parents' health problems came as a surprise to the report's author, Dr Sheila Cross, a former paediatrician at North Middlesex Hospital and a ChildLine counsellor for seven years. In the report, I know you're not a doctor, but…, Dr Cross studied around 800 of the almost 2000 children who rang ChildLine in 1994-5 and 1996-7 about their health problems.

She found that children suffering from asthma, diabetes, and other chronic illness sometimes fail to take their medicines because they do not want to be different from other children. “I know it's dangerous but I go out without my …
The Neuropharmacology of Sleep and Wakefulness
Authors: J C Gillin, W B Mendelson, N Sitaram, R J Wyatt
Journal: The Annual Review of Pharmacology and Toxicology (1978)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
High Resolution Oligonucleotide Array-CGH and Hot Spot Mutations To Select Patients for Targeted Therapies.
Authors: J. De La Cruz, V. Scott, C. Richon, B. Job, P. Dessen, M. Mathieu, S. Delaloge, J. Soria, M. Campone, F. Dalenc, T. Bachelot, V. Lazar, F. Andre
Journal: Cancer Research (2009)

Abstract Background. A high number of genomic alterations (gene amplification, mutations) have been reported in breast cancers, and could potentially be targeted in early clinical trials. In the present molecular screening program, we aim at performing CGH array and hot spot mutations for 200 patients with metastatic breast cancer, in order to drive these patients in specific early clinical trials.Patients and Methods. Patients were selected to present a metastatic breast cancer under treatment in four French Centers. DNA was extracted by Qiagen method from either primary breast cancer or metastatic lesions. The hybridizations were done on 4*44K Agilent Array CGH. The analysis was done with Analytics v3.4.40 software. The file reported amplified zones (log2ratio&amp;gt;0.84 for biopsy, 1.58 for FNA) and focused on predefined genes that encode a candidate target. Hot spot mutations cover PI3K, AKT, PTEN genes. The primary endpoint was to determine how many patients were driven to a specific clinical trial because of molecular analyses. The secondary endpoints included PFS and response rates.Results. As june 12th, 109 patients were included in the molecular screening program. CGH array was feasible and could be interpreted within one month in 85 (78%) patients. Array-CGH identified high level amplification in 57 patients (67%). As expected, the two most frequent amplicons included ERBB2 (17q11-12, 24%) and FGFR1 (8p11, 16%).The accuracy to detect ERBB2 amplification was 90%. A significant number of patients presented rare gene amplifications including ERBB4 amplification (n=1), CCND1/FGF4 amplification (n=6), FGFR2 (n=2), EGFR (n=1), VEGFB (n=4), BCR (n=1)Interestingly, only 4 patients presented TOP2A amplification. Hot spot mutations for PI3KCA, AKT, PTEN is being performedConclusion. This preliminary analysis shows that array CGH allows to identify patients who are candidate for targeted agents in phase I/II trials. Accrual will continue until 200 patients. Selected patients will be included in clinical trials in second semester of 2009 after a target validation by IHC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5067.
Hepatocellular Carcinoma in Young, Mentally Retarded Hbsag Carriers Without Cirrhosis
Authors: Ghanshyam Lohiya, Hubert Pirkle, John Hoefs, Sunita Lohiya, Vinh Trong Ngo
Journal: Hepatology (1985)

In a Californian institution for the mentally retarded, surveillance by autopsy of all deaths (n = 138) identified three cases of hepatocellular carcinoma. Hepatocellular carcinoma cases occurred in young (mean age = 26 years) male carriers of HBsAg and were not associated with cirrhosis. They were of the nonfibrolamellar oncocytic type and were rapidly fatal. Hepatocellular carcinoma incidence in HBsAg carriers was estimated to be 246 times greater than United States males.
Ailure to Demonstrate Increased Hypersensitivity to Egg Protein after Immunization with an Influenza Vaccine of the Oil-Adjuvant Type
Authors: A. D. Heggie, Y. E. Crawford, L. F. Miller
Journal: New England Journal of Medicine (1960)

THE use of vaccines of the mineral-oil-adjuvant type in influenza-immunization procedures has the potential advantage of reducing the number of injections and amount of antigen required while producing antibodies in high titer for a prolonged period. Untoward reactions associated with these adjuvant preparations have been minor and relatively few, except when certain impure lots of the emulsifying agent, arlacel A, were employed. The impurities in certain lots of this agent have been implicated in the development of cysts and sterile abscesses after immunization.1 , 2 A potential hazard exists, however, as with aqueous preparations, that in addition to immunity to the desired . . .
<i>TP53</i> Mutations in Favorable-Risk Wnt/Wingless-Subtype Medulloblastomas
Authors: Janet C. Lindsey, Rebecca M. Hill, Hisham Megahed, Meryl E. Lusher, Ed C. Schwalbe, Michael Cole, Twala L. Hogg, Richard J. Gilbertson, David W. Ellison, Simon Bailey, Steven C. Clifford
Journal: Journal of Clinical Oncology (2011)
Evidence for Success of Caloric Restriction in Weight Loss and Control: Summary of Data from Industry
Authors: Frederick N. Hyman
Journal: Annals of Internal Medicine (1993)

Data voluntarily supplied by industry were examined to evaluate the success of commercial weight loss programs and products. Information about the safe loss of weight, the maintenance of this lowered weight, and resultant health benefits were reviewed. Information was received from companies that produce over-the-counter preparations designed for persons with a small weight loss goal and from physician-supervised programs for morbidity obese persons placed on very-low-calorie diets. Regardless of the products used, successful weight loss and control was limited and required individualized programs consisting of restricted caloric intake, behavior modification, and exercise. Although some manufacturers of physician-supervised weight loss products for obese persons hav defined the effectiveness of their programs with controlled clinical studies, other industry programs have only begun to accurately assess their effectiveness or safety. Given the importance to public health of reducing obesity, rigorous studies on current weight control practices should be pursued aggressively.
Nondisjunction in Males: Commoner Than Suspected?
Authors: David A. Lynch
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The idea that the mother is responsible for all trisomic conditions is commonly encountered from both patients and members of the medical profession. At the risk of striking a blow against the forces of male chauvinism, we think that nondisjunction in spermatogenesis may be playing a greater role in the etiology of Down's syndrome and other trisomies than is commonly thought. Shuttleworth, in his work<i>Mentally Deficient Children</i>(London, HK Lewis &amp; Co, 1895), was the first to observe that children with mongolism tend to be born to older parents. Jenkins<sup>1</sup>showed that the incidence of mongolism increases with increasing age, both of the father and of the mother, and that the age of the mother was a better predictor of occurrence of the syndrome. By the use of the partial correlation technique followed by regression analysis in a population of 150 families, a study by
Education on prescribing can be improved
Authors: Anthony J Smith, Tina Tasioulas
Journal: BMJ (2002)

EDITOR—The personal view from Ellis prompts us to respond—particularly as one of us (AJS) was for many years a teacher of pharmacology in the medical school at the university where she is a student.1

About 10 years ago, Australia incorporated the promotion of the quality use of medicines into its fledgling national policy on medicines. Turning policy into reality takes time, but, for the improvement of prescribing practice in particular, a key next step was the creation in 1998 of the National Prescribing Service …
A Fee-Nom-in-Hum and an Expotition
Authors: Julie Morris
Journal: BMJ (2004)

This paper by Knight1 describes a great Expotition into the 100 Aker Wood to investigate the puzzle, “Isn't it funny how emboli race to the same place?” by throwing pine cones from My Bridge into the stream and tracking them, in a Big Adventure, to see where they would end up.

The study seems very interesting, and the results would make my friend Eeyore think, “That accounts for a Good Deal. It Explains Everything. No Wonder.” But I am not sure I understand everything the Clever …
Paralytic Poliomyelitis In Unvaccinated Mother
Authors: Leonard J. Morse
Journal: JAMA (1967)

To the Editor:—  The letter by Dr. Edward B. Shaw (198:1224, 1966) regarding our article Vaccine-Acquired Paralytic Poliomyelitis in an Unvaccinated Mother (197:1034, 1966) prompts this reply. It was not the intention of the authors to discourage the use of live oral poliovirus vaccine. The initial sentence of the article stated clearly that the use of live oral poliovirus vaccine is responsible for the almost complete elimination of paralytic poliomyelitis. However, because the virus from the vaccine can be transmitted to persons handling the excreta of recently immunized infants, it is felt that parents and attendants should be protected by immunization with live oral poliovirus vaccine.  The illness and the results of diagnostic virus studies support the diagnosis of paralytic poliomyelitis in the patient described. The patient's residual neurologic deficit was striking paralysis of the left upper and both lower extremities. In our judgment, the clinical course was
Successful Treatment with Voriconazole of Invasive Aspergillosis in Chronic Granulomatous Disease
Authors: LOUIS G. van ‘t HEK, PAUL E. VERWEIJ, CORRY M. WEEMAES, ROELOF van DALEN, JAN-BART YNTEMA, JACQUES F. MEIS
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

A 5-year-old boy with chronic granulomatous disease (CGD) was treated with amphotericin B for an invasive pulmonary Aspergillus nidulans infection. The infection progressed during 6 wk of treatment despite the addition of interferon- γ (IFN- γ ), filgrastim, and transfusions with donor granulocytes. Treatment with a novel antifungal triazole, voriconazole, resulted in an excellent clinical response. van ‘t Hek LG, Verweij PE, Weemaes CM, van Dalen R, Yntema J-B, Meis JF. Successful treatment with voriconazole of invasive aspergillosis in chronic granulomatous disease.
Midstream urine sampling is still helpful
Authors: S. J. Srirangam, D. Bondin
Journal: BMJ (2010)

On the basis of Little and colleagues’ study of five different approaches in managing urinary tract infections in primary care,1 Mangin concludes that testing midstream urine samples is unhelpful and expensive.2 However, the study recruited 309 patients from 62 practices over two years, with an average of fewer than three …
Principles of Pharmacology: Basic Concepts and Clinical Applications
Authors: James P. Morgan
Journal: JAMA (1997)

<i>Principles of Pharmacology</i>is intended as a concise reference book for medical and graduate students, residents, postdoctoral fellows, faculty members, and health professionals in medicine, pharmacy, dentistry, veterinary medicine, nursing, and public health. The volume is divided into sections, each the primary responsibility of a section editor or coeditors. As such, the strength of the text depends on the quality of the section editors and their selected authors. Many outstanding clinicians and scientists appear in the listing of "Editors, Authors, and Advisors"; this list is truly international and includes representatives from around the world. The international flavor is reflected in a supplement to the text about new drug approval in Japan. Most of this 1796-page text, however, is devoted to scientific and clinical aspects of pharmacology and therapeutics. The first section on general principles includes a comprehensive review of pharmacodynamics and pharmacokinetics and a discussion of drug development and the