tbuckley/cabot-search huggingface dataset:
Loss of p16 Expression Is of Prognostic Significance in Locally Advanced Prostate Cancer: An Analysis From the Radiation Therapy Oncology Group Protocol 86–10
Authors: A. Chakravarti, K. Heydon, C.L. Wu, E. Hammond, A. Pollack, M. Roach, H. Wolkov, P. Okunieff, J. Cox, J. Fontanesi, R. Abrams, M. Pilepich, W. Shipley
Journal: Journal of Clinical Oncology (2003)

The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16, are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10.Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival.Loss of p16 expression, as defined by expression was significantly associated with reduced overall survival (P =.039), disease-specific survival (P =.006), and higher risk of local progression (P =.0007) and distant metastasis (P =.026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P =.0078) and increased risk of local failure (P =.0035) and distant metastasis (P =.026). A borderline association with reduced overall survival (P =.07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P =.028) and multivariate analysis (P =.043), but carried no other significant outcome associations.Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.
Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities
Authors: Brian J. Nickoloff, Frank O. Nestle
Journal: Journal of Clinical Investigation (2004)

Chronic and excessive inflammation in skin and joints causes significant morbidity in psoriasis patients. As a prevalent T lymphocyte–mediated disorder, psoriasis, as well as the side effects associated with its treatment, affects patients globally. In this review, recent progress is discussed in the areas of genetics, the immunological synapse, the untangling of the cytokine web and signaling pathways, xenotransplantation models, and the growing use of selectively targeted therapies. Since psoriasis is currently incurable, new management strategies are proposed to replace previous serendipitous approaches. Such strategic transition from serendipity to the use of novel selective agents aimed at defined targets in psoriatic lesions is moving rapidly from research benches to the bedsides of patients with this chronic and debilitating disease.
Ben Castleman — Champion of the CPC
Authors: Robert E. Scully
Journal: New England Journal of Medicine (1982)

Benjamin Castleman, M.D., Shattuck Professor of Pathological Anatomy, Emeritus, at Harvard Medical School, and Pathologist in Chief at the Massachusetts General Hospital from 1951 to 1974, died on June 29 at the age of 76 years. "B.C.," as his residents referred to him, had a career in medicine that was remarkable for its range and influence on medical care. A skilled clinical diagnostician as well as a superb pathologist, he trained many residents and younger colleagues to emulate his approach to the pathological specimen — first make an accurate diagnosis and then, of equal importance, consider its impact on the . . .
Urine neopterin concentrations and activity of psoriasis
Authors: N. Sepp, S. Benedikter, H. Kofler, H. Wachter, D. Fuchs
Journal: British Journal of Dermatology (1993)

Journal Article Urine neopterin concentrations and activity of psoriasis Get access N. Sepp, N. Sepp Department of Dermatology, University of Innsbruck. A‐6020 Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar S. Benedikter, S. Benedikter Department of Dermatology, University of Innsbruck. A‐6020 Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar H. Kofler, H. Kofler Department of Dermatology, University of Innsbruck. A‐6020 Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar H. Wachter, H. Wachter Institute of Medical Chemistry and Biochemistry, University of Innsbruck. A‐6020 Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar D. Fuchs D. Fuchs Institute of Medical Chemistry and Biochemistry, University of Innsbruck. A‐6020 Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 4, 1 October 1993, Page 498, https://doi.org/10.1111/j.1365-2133.1993.tb03183.x Published: 01 October 1993
At Southwest Foundation, Scientists Run Show—but Research Animals Are Essential Stars
Authors: Marsha F. Goldsmith
Journal: JAMA (1989)

ANIMAL WELFARE is a sine qua non at the Southwest Foundation for Biomedical Research in San Antonio, Tex. Without its approximately 3500 nonhuman primates and 4000 animals of other species, the renowned facility not far from the Alamo would be out of business. Unless healthy animals are used, experimental conclusions might be invalid or misleading.  Five full-time veterinarians care for the animals, supporting the work of more than 50 research scientists. Duncan Wimpress, PhD, is president of the foundation.  Some 'Pensioned'  A visitor may become acquainted with some of the 3300 baboons (of all five species, including a few pensioned-off mandrills and several of the showy hamadryas baboon revered in ancient Egypt) and approximately 200 chimpanzees of all ages from infants to retirees.  In two 6-acre breeding corrals that seem huge in themselves but are only dots on its 800-acre property, the foundation houses more baboons than any similar facility
Perhaps the Ultimate Communications Challenge: Informing the Nation of a President's Condition
Authors: Randy Ross
Journal: JAMA (1987)

DENNIS O'LEARY, MD, had lectured in Room 101 many times. But on a spring night in Washington, DC, in 1981, he faced more than the usual inquiring George Washington University medical students. He faced the people and machines of what theWashington Postlater called a near-ugly press corps. It was just hours after President Reagan had been shot and the nation awaited the prognosis.  In the midst of glaring television lights and blaring reporters, O'Leary, pressed into service as medical spokesperson, displayed grace under pressure. He explained the procedures being used on the President in lay terms. He held up his arm to show the site of an incision. He became a symbol of calm and reassurance.  Perhaps no physician before or since has faced greater pressure in dealing with the news media. Now, six years after that historic event, O'Leary, who left his position as dean for clinical
Renal Transplantation
Authors: Bruce Kaplan, Herwig-Ulf Meier-Kriesche
Journal: Journal of the American Society of Nephrology (2004)

In this issue of JASN , Doyle et al. give an historic overview of organ transplantation with emphasis on renal transplantation ([1][1]). In this overview the story is one of almost unparalleled success. As pointed out by Doyle et al. the major barriers to successful renal transplantation in the
Lumbopleural Cerebrospinal Fluid Shunt Assessment With Tc-99m DTPA Scintigraphy
Authors: FARSHID BOZORGI, LEONARD P. CONNOLLY, S. TED TREVES
Journal: Clinical Nuclear Medicine (1997)

Lumbopleural shunts are occasionally required in the treatment of hydrocephalus when more commonly used shunts fail. Patency of a lumbopleural shunt can be confirmed with scintigraphy after subarachnoid instillation of Tc-99m DTPA by lumbar puncture, as illustrated in the presented case.
PSGL-1 blockade using a unique monoclonal antibody 4RA10 reduces neointima formation after arterial injury in apolipoprotein-E deficient mice
Authors: J.William Phillips, Kurt G. Barringhaus, John M. Sanders, Ann C. Czarnik, Dietmar Vestweber, Klaus Ley, Ian J. Sarembock
Journal: Journal of the American College of Cardiology (2002)
Relationship between the tautomeric structures of curcumin derivatives and their Aβ-binding activities in the context of therapies for Alzheimer's disease
Authors: Daijiro Yanagisawa, Nobuaki Shirai, Tomone Amatsubo, Hiroyasu Taguchi, Koichi Hirao, Makoto Urushitani, Shigehiro Morikawa, Toshiro Inubushi, Masanari Kato, Fuminori Kato, Kyuya Morino, Hirohiko Kimura, Ichiro Nakano, Chikako Yoshida, Takashi Okada, Mitsuo Sano, Yoshiko Wada, Ken-nosuke Wada, Akitsugu Yamamoto, Ikuo Tooyama
Journal: Biomaterials (2010)
PWE-042 The relevance of the siewert classification in the era of multimodal therapy for adenocarcinoma of the gastro-oesophageal junction
Authors: Nathan J. Curtis, Fergus Noble, Ian S. Bailey, Jamie J. Kelly, James P. Byrne, Timothy J. Underwood
Journal: Gut (2012)

<h3>Introduction</h3> Since the early 1980s the Siewert classification has been used to plan treatment for tumours of the gastro-oesophageal junction. However, the relationship between tumour site and survival has not been conclusively demonstrated, with conflicting outcomes in the largest series, before the widespread application of neoadjuvant chemotherapy. The aim of this study was to evaluate whether there were differences in the biology and clinical characteristics of adenocarcinomas by Siewert type, in a contemporary cohort of patients, in whom the majority had received neoadjuvant chemotherapy. The relationship of the surgical approach and tumour site with patient survival was also assessed. <h3>Methods</h3> A prospective database was reviewed for all patients who underwent resection for adenocarcinoma of the distal oesophagus and gastro-oesophageal junction from 2005 to 2011. In our unit, based on pre-operative assessment, distal oesophageal, type I and II tumours are treated as oesophageal cancer, with transthoracic procedures. Type III tumours are treated as gastric cancer with an abdominal approach. Classification systems used for analysis included TNM 7 for staging, Clavien-Dindo for grading complications and Siewert with final tumour site determined from the pathological specimen. Survival was estimated by Kaplan–Meier analysis excluding inpatient deaths (n=4) and R1 resections (n=42). <h3>Results</h3> 216 patients underwent oesophagogastric resection: 133 for type I, 51 for type II and 33 for type III tumours. Median follow-up was 2.94 years. 62.5% of patients received neoadjuvant chemotherapy with no difference between groups. There were no significant differences in age, sex, pT stage, pN stage, pM stage, ASA, or inpatient complications between patients with adenocarcinoma based on their Siewert classification. Type I tumours were significantly associated with coexisting Barrett9s metaplasia (presence of Barrett9s: Type I 58.3%, Type II 21.6%, Type III 9.1%; pType II &gt; Type I). Median overall survival was significantly shorter for more distal tumours (Type I: 4.96 years vs Type II: 3.3 years vs Type III: 2.64 years; p=0.04). The surgical approach did not influence survival for all tumour types and had no impact on the rate or severity of complications. <h3>Conclusion</h3> This study demonstrates significant differences in the biological characteristics of adenocarcinomas of the gastro-oesophageal junction based on their anatomical topographical sub-classification. In the era of multimodal therapy overall survival is worse for tumours arising at or below the gastro-oesophageal junction compared with oesophageal tumours. <h3>Competing interests</h3> None declared.
Acid-Base Relations between Blood and Cerebrospinal Fluid in Normal Subjects and Patients with Respiratory Insufficiency
Authors: Charles R. Merwarth, Herbert O. Sieker, Felice Manfredi
Journal: New England Journal of Medicine (1961)

THE occurrence of a variety of central-nervous-system abnormalities in association with either under-ventilation or overventilation is well known.1 , 2 Clinically, severe disturbances of nervous-system function progressing to coma frequently occur with ventilatory insufficiency.3 In this situation anoxia is present, and, although the administration of oxygen corrects the hemoglobin unsaturation, hypercapnia may worsen, with further Central-nervous-system deterioration. More efficient ventilation, with a consequent fall in carbon dioxide tension (pCO2), results in clinical improvement. On the other hand, abnormally low pCO2 and high pH of arterial blood is associated with giddiness, confusion, flushing, paresthesias and spasmodic muscle contraction. These symptoms . . .
Breast cancer screening does not save lives, study says
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Breast cancer screening in “real world” situations is not effective in preventing mortality, says a US case control study. The study, one of the largest completed to date looking at the effectiveness of breast cancer screening, was published in the Journal of the National Cancer Institute (2005;97: 1035-43).

Randomised controlled studies have shown that breast cancer screening prevents deaths. Many organisations recommend screening by clinical examination and mammography every year or two for women aged 40 or older.

“We observed no appreciable association between breast cancer mortality and screening history, [regardless of age or risk level],” the authors write. “Our findings may, therefore, reflect a possible reduction in the accuracy of screening as it moves from highly controlled randomised …
Measurement of gut hormonal peptides in biopsies from human stomach and proximal small intestine.
Authors: M G Bryant, S R Bloom, J M Polak, S Hobbs, W Domschke, S Domschke, P Mitznegg, H Ruppin, L Demling
Journal: Gut (1983)

Using sensitive and specific radioimmunoassays, concentrations of hormonal peptides have been measured in small biopsies taken from the human stomach, duodenum, and proximal jejunum. Comparison is made of these hormone concentrations and the number of respective endocrine cells present determined by quantitative immunocytochemistry. Immunoreactive somatostatin, VIP, motilin, and gastrin were detected in all regions examined, whereas secretin and GIP were undetectable in antral extracts. Enteroglucagon-like immunoreactivity was present only at and beyond the ligament of Treitz, although a few enteroglucagon-producing cells were shown by immunocytochemistry in the duodenum. The variation of hormone concentration was found to be small in these biopsies of normal tissue within each region of the gut examined, indicating that representative hormone concentrations may be reliably obtained from small biopsy tissues. An attempt has been made to establish reference values for gut hormone concentrations in such biopsies; this may allow future study of any changes in concentration that may occur in pathological conditions.
Tracheal Flora Following Tracheostomy: Effect of Conventional and Meticulous Care.
Authors: James A. Reinarz
Journal: Annals of Internal Medicine (1969)

s1 May 1969Tracheal Flora Following Tracheostomy: Effect of Conventional and Meticulous Care.James A. Reinarz, M.D., T. E. Murphy, M.D., D. E. Wells, M.D.James A. Reinarz, M.D.Search for more papers by this author, T. E. Murphy, M.D.Search for more papers by this author, D. E. Wells, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1091_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTracheostomy is frequently required in respiratory failure, burns, and pulmonary hygiene. Pseudomonads may colonize tracheostomies and may cause nosocomial pulmonary infections. Many reports state that pseudomonads are determental and imply that meticulous tracheostomy care can prevent pseudomonad (and other bacterial) colonization. While this is an attractive hypothesis, it has never been tested. Hence, standard tracheostomy care—two bottles and reusable catheter—was compared with meticulous care—no solutions, single-use disposable catheter, and sterile disposable gloves. Quantitative cultures of deep tracheostomy aspirates, peritracheostomy skin, inhalation therapy equipment, catheters, solutions, and room air were obtained within 24 hr and sequentially for 12 days in 19... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Lackland Air Force Base, Texas PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1091-1092KeywordsBurnsCathetersHygieneInhalationNosocomial infectionsPseudomonas infectionsPulmonary diseasesRespiratory failureTracheostomyVentilators Issue Published: 1 May 1969 PDF downloadLoading ...
Hypertension-associated point mutations in the adducin alpha and beta subunits affect actin cytoskeleton and ion transport.
Authors: G Tripodi, F Valtorta, L Torielli, E Chieregatti, S Salardi, L Trusolino, A Menegon, P Ferrari, P C Marchisio, G Bianchi
Journal: Journal of Clinical Investigation (1996)

The adducin heterodimer is a protein affecting the assembly of the actin-based cytoskeleton. Point mutations in rat adducin alpha (F316Y) and beta (Q529R) subunits are involved in a form of rat primary hypertension (MHS) associated with faster kidney tubular ion transport. A role for adducin in human primary hypertension has also been suggested. By studying the interaction of actin with purified normal and mutated adducin in a cell-free system and the actin assembly in rat kidney epithelial cells (NRK-52E) transfected with mutated rat adducin cDNA, we show that the adducin isoforms differentially modulate: (a) actin assembly both in a cell-free system and within transfected cells; (b) topography of alpha V integrin together with focal contact proteins; and (c) Na-K pump activity at V(max) (faster with the mutated isoforms, 1281 +/- 90 vs 841 +/- 30 nmol K/h.mg pt., P < 0.0001). This co-modulation suggests a role for adducin in the constitutive capacity of the epithelia both to transport ions and to expose adhesion molecules. These findings may also lead to the understanding of the relation between adducin polymorphism and blood pressure and to the development of new approaches to the study of hypertension-associated organ damage.
“Annexinopathies” — A New Class of Diseases
Authors: Jacob H. Rand
Journal: New England Journal of Medicine (1999)

The annexins were first described as a family of proteins in 1990,1 and they have since been extensively reviewed.2 Individual members of the family had previously been isolated, characterized, and assigned a variety of names. The nomenclature depended on the particular scientific discipline of the investigators or on the tissue from which the proteins had been isolated. The proteins included the placental anticoagulant proteins, placental proteins, vascular anticoagulant proteins, lipocortins, and endonexins. With amino acid and nucleotide sequencing came the recognition that these various proteins were highly homologous and shared the property of binding calcium and phospholipids. So far, over . . .
Radionuclide ventriculography for assessment of absolute right and left ventricular volumes in children.
Authors: M D Parrish, T P Graham, M L Born, J P Jones, R J Boucek, C L Partain
Journal: Circulation (1982)

We determined absolute right and left ventricular volumes and cardiac output from the equilibrium radionuclide angiogram in 26 children, ages 3 months to 18 years, with diverse types of heart disease. We validated these results by comparing them with left ventricular (20 patients) and right ventricular (16 patients) cineangiographic volumes and cardiac output. Radionuclide volumes and cardiac outputs were determined in two ways: by a geometric method (area-length for left ventricle, Simpson's rule for right ventricle) and by a count-based method (correcting ventricular regional counts for frame duration, acquisition time, venous blood counts and attenuation). Both methods for estimating left ventricular end-diastolic volume compared favorably with cineangiography (correlation coefficients greater than 0.90). The count-based method also correlated well for the right ventricle. End-systolic measurements were not possible. Count-based assessment of cardiac output also correlated well with cineangiographic values. We conclude that right and left ventricular volumes and cardiac output can be reliably measured in children with equilibrium radionuclide ventriculography.
Early and Late Effects of Coronary Artery Occlusion on Canine Purkinje Fibers
Authors: RALPH LAZZARA, NABIL EL-SHERIF, BENJAMIN J. SCHERLAG
Journal: Circulation Research (1974)

The electrophysiological characteristics of subendocardial Purkinje and myocardial cells were studied during acute (within 30 minutes) and chronic (after 10 days) phases of myocardial infarction. Endocardial Purkinje and myocardial electrograms were recorded in vivo with bipolar electrodes before and after occlusion of the anterior descending coronary artery. Also, intracellular and extracellular potentials were recorded in vitro from the endocardial surface of infarcted regions of hearts excised during the acute and chronic phases. In the acute phase, Purkinje and myocardial potentials within the ischemic zone deteriorated in vivo, but they were not markedly delayed. Intracellular recordings in vitro showed partial depolarization of both Purkinje and myocardial cells. In the chronic phase, extracellular and intracellular Purkinje potentials recorded in vivo and in vitro from the infarcted zone usually did not differ from normal. No myocardial potentials were recorded from the endocardial surface of the chronic infarcts. Thus, subendocardial Purkinje and myocardial cells are affected early in infarction, but many Purkinje cells survive and return to normal.
Familial risks of oral clefts
Authors: Melissa Lees
Journal: BMJ (2008)

Risk of recurrence is higher with cleft palate only

Oral clefts, including cleft lip with or without cleft palate and cleft palate only, have a high rate of familial recurrence compared with many birth defects.1 The cleft can occur in association with other congenital abnormalities, sometimes as part of an underlying recognisable syndrome, or more often as an isolated defect. Inheritance is complex and related to environmental and genetic factors.2 Although a genetic component exists, the precise genetic basis is unclear.

The risks of having a child with an oral cleft that are used when counselling families at increased risk are based on empirical figures derived from studies that have several limitations, such as inclusion of syndromic cases, the grouping of all oral clefts together, incomplete ascertainment, and a lack of longitudinal data.

In their accompanying paper, Sivertson and colleagues report a longitudinal population based study of the risk of non-syndromic oral clefts in Norwegian families.3 They analyse the type and the severity of the cleft in the index case. Norway has an excellent model for generating useful epidemiological data for oral …