tbuckley/cabot-search huggingface dataset:
Colorectal Cancer: Molecules and Populations
Authors: J. D. Potter
Journal: JNCI Journal of the National Cancer Institute (1999)

The epidemiology and molecular biology of colorectal cancer are reviewed with a view to understanding their interrelationship. Risk factors for colorectal neoplasia include a positive family history, meat consumption, smoking, and alcohol consumption. Important inverse associations exist with vegetables, nonsteroidal anti-inflammatory drugs (NSAIDs), hormone replacement therapy, and physical activity. There are several molecular pathways to colorectal cancer, especially the APC (adenomatous polyposis coli)-beta-catenin-Tcf (T-cell factor; a transcriptional activator) pathway and the pathway involving abnormalities of DNA mismatch repair. These are important, both in inherited syndromes (familial adenomatous polyposis [FAP] and hereditary nonpolyposis colorectal cancer [HNPCC], respectively) and in sporadic cancers. Other less well defined pathways exist. Expression of key genes in any of these pathways may be lost by inherited or acquired mutation or by hypermethylation. The roles of several of the environmental exposures in the molecular pathways either are established (e.g., inhibition of cyclooxygenase-2 by NSAIDs) or are suggested (e.g., meat and tobacco smoke as sources of specific blood-borne carcinogens; vegetables as a source of folate, antioxidants, and inducers of detoxifying enzymes). The roles of other factors (e.g., physical activity) remain obscure even when the epidemiology is quite consistent. There is also evidence that some metabolic pathways, e.g., those involving folate and heterocyclic amines, may be modified by polymorphisms in relevant genes, e.g., MTHFR (methylenetetrahydrofolate reductase) and NAT1 (N-acetyltransferase 1) and NAT2. There is at least some evidence that the general host metabolic state can provide a milieu that enhances or reduces the likelihood of cancer progression. Understanding the roles of environmental exposures and host susceptibilities in molecular pathways has implications for screening, treatment, surveillance, and prevention.
Evolution of a hereditary cardiac conduction and muscle disorder: a study involving a family with six generations affected.
Authors: H L Graber, D V Unverferth, P B Baker, J M Ryan, N Baba, C F Wooley
Journal: Circulation (1986)

This study describes six generations of a family with autosomal dominant cardiac conduction system and myocardial disease with recognizable clinical stages. A 20 year follow-up of nine family members, a medical questionnaire of 196, electrocardiographic screening of 91, noninvasive testing of 20, and catheterization with endomyocardial biopsy of six are the basis of this report. The clinical stages are as follows: Stage I occurs in the second and third decades of life and is characterized by an absence of symptoms, normal heart size, sinus bradycardia, and premature atrial contractions. Stage II is marked by first-degree atrioventricular block in the third and fourth decades. Stage III occurs in the fourth and fifth decades and is accompanied by chest pain, fatigue, lightheadedness, and advanced atrioventricular block followed by the development of atrial fibrillation or flutter. Stage IV, in the fifth and sixth decades of life, is characterized by congestive heart failure and recurrent ventricular arrhythmias. Light microscopy of right ventricular endomyocardial biopsy specimens from patients in stage II revealed very mild fibrosis; electron microscopy of the specimens demonstrated mild dilatation of tubules, mitochondrial swelling, and minimal myofibrillar loss. Biopsy specimens from patients with stage III disease were similar to those from patients with stage II disease except for an increase of myofibrillar loss. The stage IV specimens had diffuse fibrosis and more severe tubular dilatation, mitochondrial cristolysis, and myofibrillar loss. At autopsy in the proband, the atrial changes were more severe than the ventricular and were especially marked in the sinoatrial and atrial myocardium. Early recognition of the disease and use of pacemakers and antiarrhythmic agents have proved beneficial for affected family members. Thorough family studies of patients with conduction system disease and/or dilated cardiomyopathy are necessary to better understand the hereditary basis and natural course of this category of disease.
EDUCATIONAL POSSIBILITIES OF A STATE PSYCHOPATHIC HOSPITAL
Authors: Franklin G. Ebaugh
Journal: American Journal of Psychiatry (1928)

A summary of the educational possibilities of a state psychopathic hospital may be given as follows: A. INTRA-MURAL EDUCATIONAL POSSIBILITIES. 1. Adequate teaching of medical students emphasizing a diminution in didactic work and increasing actual ward contacts with patients. 2. Educational possibilities through regular group conferences with relatives. This should be a vital activity of any psychopathic hospital. 3. Education through the medium of patients discharged from the hospital. Each patient should be given written advice analogous to that given in other medical fields. 4. An active consultation service will help break down the barrier between psychiatry and the other fields of medicine. In this connection it is important to have joint clinics with representatives from other fields. B. EXTRA-MURAL EDUCATIONAL POSSIBILITIES. 1. Further contacts with the courts and the legal profession should be made. In this connection a brief course in psychiatry in the law school has been given. 2. The traveling clinic has been found to be of great educational value, especially since it furthers contacts with schools, social and health organizations in all districts. It should pave the way for the establishment of permanent base clinics and it is hoped that eventually a permanent traveling team will be created.
Improvement of Survival in Patients with Diffuse Panbronchiolitis Treated with Low-dose Erythromycin
Authors: SHOJI KUDOH, ARATA AZUMA, MASAHIKO YAMAMOTO, TAKATERU IZUMI, MASAYUKI ANDO
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Diffuse panbronchiolitis (DPB) is a chronic inflammatory disease of the airways with a high rate of mortality despite treatment with a combination of antibiotics and the use of supportive therapy such as oxygen administration. Low-dose erythromycin therapy (EM) (400 to 600 mg/d) has been found to improve the survival of patients with DPB, and most patients with DPB in Japan have been treated with this erythromycin regime since 1984. The purpose of this study was to evaluate the effects of treatment with erythromycin on the survival rate of patients with DPB in Japan. We compared the survival rates of 498 patients with DPB after dividing them into three groups according to the date of their first medical examination (Group a: 1970–1979, Group b: 1980–1984, Group c: 1985–1990). DPB had been diagnosed in these patients using the criteria of the Ministry of the Health and Welfare Diffuse Lung Disease Committee (MHW-DLDC), which includes chronic productive cough, shortness of breath, presence of roentgenologically smoldering symmetrical granular shadows in the middle and lower lung fields, limitation of airflow without decrease in Dl CO, elevated serum cold hemagglutinin titers, and/or narrowing bronchiolus with infiltration of lymphocytes and foamy alveolar macrophages. These patients were registered in the DPB research group of the Ministry of Health and Welfare (MHW). Survival rates were statistically compared using the generalized-Wilcoxon test. The survival rate of Group c was significantly higher than that of Groups a (p < 0.0001) and b (p < 0.0001). In Group c, eight of 87 patients died; five died in the EM nontreated subgroup (n = 24), and three died in the EM-treated subgroup (n = 63). There was a significant difference in the survival rates between the two subgroups in Group c (p < 0.001). Treatment with EM was associated with a significant improvement in the rate of survival of patients with DPB. The efficacy of EM treatment increased the survival rate of patients with DPB, which was more significant in the older than in the younger patients.
Prominent Renal Expression of a Murine Leukemia Retrovirus in Experimental Systemic Lupus Erythematosus
Authors: Jessy J. Alexander, Amit K. Saxena, Lihua Bao, Alexander Jacob, Mark Haas, Richard J. Quigg
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. A role for retroviruses in human systemic lupus erythematosus (SLE) and in mouse lupus models such as the New Zealand Black and White mice (NZB/W) strain has been postulated. This study compared the gene profile of nephritic NZB/W kidney with nondiseased NZW controls. The most highly upregulated gene (5.5-fold) hybridized with an expressed sequence tag on a cDNA microarray, which was sequenced and found to correspond with an endogenous murine retrovirus related to the Duplan strain (EDV, L08395). NZB/W kidney contained the full-length 4.2-kb EDV transcript. By 4 wk of age in NZB/W mice, an age preceding renal histologic disease, the EDV transcript was more than threefold increased relative to NZB or NZW control strains. This upregulated expression tended to fall with progression of renal histologic disease. By in situ hybridization, the EDV transcript was highly expressed in tubules of NZB/W mice. There was also upregulated expression of EDV transcript in NZB/W lung and brain, sites of inflammation in this strain, but not in spleen or liver. Thus, using microarrays, the most highly expressed gene in mouse lupus nephritis corresponded to an endogenous retrovirus. This retroviral transcript was highly expressed in the kidneys of lupus mice and tended to decline with advancement of disease. The remarkable upregulation of the EDV transcript only in the setting of active disease suggests this transcript is involved in inflammatory disease.
Frontier Justice: A Contribution to the Theory of Child Battery
Authors: WILLIAM R. FLYNN
Journal: American Journal of Psychiatry (1970)

Child abuse, the author believes, is often dependent upon structural and dynamic elements within the adult. He reports two cases of mothers who beat one of their children and concludes that defective defense structures of the ego are frequently responsible for child abuse; abusing parents. he finds, tend to project their anger onto their children, while denying and repressing it in themselves.
Sex and drugs in popular movies: an analysis of the top 200 films
Authors: Hasantha Gunasekera, Simon Chapman, Sharon Campbell
Journal: Journal of the Royal Society of Medicine (2005)

We analyse the portrayal of sex and drug use in the most popular movies of the last 20 years using the Internet Movie Database list of the top 200 movies of all time. Films released or set prior to the HIV era (pre 1983), animated, not about humans or G/PG rated, were excluded. Films were reviewed by one of two teams of two observers using a data extraction sheet tested for inter-rater reliability. Sexual activity, sexually transmitted disease (STD) prevention, birth control measures, drug use and any consequences discussed or depicted were recorded. There were 53 sex episodes in 28 (32%) of the 87 movies reviewed. There was only one suggestion of condom use, which was the only reference to any form of birth control. There were no depictions of important consequences of unprotected sex such as unwanted pregnancies, HIV or other STDs. Movies with cannabis (8%) and other non-injected illicit drugs (7%) were less common than those with alcohol intoxication (32%) and tobacco use (68%) but tended to portray their use positively and without negative consequences. There were no episodes of injected drug use. Sex depictions in popular movies of the last two decades lacked safe sex messages. Drug use, though infrequent, tended to be depicted positively. The social norm being presented is concerning given the HIV and illicit drug pandemics.
Fine-mapping of an increased total IgE susceptibility gene on chromosome 2q: Analysis of CTLA-4 and CD28
Authors: Timothy D Howard, Dirkje S Postma, Gregory A Hawkins, Gerard H Koppelman, Siqun L Zheng, Jianfeng Xu, Deborah A Meyers, Eugene R Bleecker
Journal: Journal of Allergy and Clinical Immunology (2002)
Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans
Authors: Norihisa Sakamoto, Kazuhide Tsuji, Linda M. Muul, Ann M. Lawler, Emanuel F. Petricoin, Fabio Candotti, Julia A. Metcalf, Jorge A. Tavel, H. Clifford Lane, Walter J. Urba, Bernard A. Fox, Ajit Varki, Joan K. Lunney, Amy S. Rosenberg
Journal: Blood (2007)
Phase II study of weekly docetaxel in patients with metastatic breast cancer
Authors: T. Aihara, Y. Kim, Y. Takatsuka
Journal: Annals of Oncology (2002)

BackgroundThis study was conducted to investigate the efficacy and toxicity of weekly docetaxel administration in patients with metastatic breast cancer.Patients and methodsThirty-seven women were treated with 1 h infusions of docetaxel at 40 mg/m2/week after pre-medication with 8 mg dexamethazone. Each cycle consisted of three consecutive weekly treatments followed by a 1 week rest. All patients were assessed for toxicity; five patients were not assessable for clinical response, time to progression (TTP) and overall survival (OS) because of early treatment failure, but they were included in intention-to-treat analysis.ResultsPatients received a median of four cycles (range, 1–9), with a median dose intensity of 28 mg/m2/week (range 22–30) and a median relative dose intensity of 0.95 (range 0.73–1.0). No patients showed complete response, whereas 14 had partial response, which accounted for 38% of objective response rate [95% confidence interval (CI) 22% to 53%]. In addition, three patients (8%, 95% CI 0% to 17%) had stable disease over 6 months. Clinical responses were achieved at a median of three cycles (range 1–4 cycles). The median TTP and OS were 5 and 12 months, respectively. The weekly docetaxel regimen was generally well tolerated. About half of the patients experienced grade ≥1 neutropenia; only 19% had grade 3/4 neutropenia, including one case of grade 4. No febrile neutropenia was observed and fluid retention syndrome was uncommon. Non-hematologic toxicity, however, such as asthenia/fatigue, nail damage, tearing or hearing disorders, was seen with successive treatment cycles.ConclusionsWeekly docetaxel at 40 mg/m2/week is an active and feasible regimen for patients with metastatic breast cancer.
Cytosolic Phospholipase A2α–deficient Mice Are Resistant to Collagen-induced Arthritis
Authors: Martin Hegen, Linhong Sun, Naonori Uozumi, Kazuhiko Kume, Mary E. Goad, Cheryl L. Nickerson-Nutter, Takao Shimizu, James D. Clark
Journal: The Journal of Experimental Medicine (2003)

Pathogenic mechanisms relevant to rheumatoid arthritis occur in the mouse model of collagen-induced arthritis (CIA). Cytosolic phospholipase A2α (cPLA2α) releases arachidonic acid from cell membranes to initiate the production of prostaglandins and leukotrienes. These inflammatory mediators have been implicated in the development of CIA. To test the hypothesis that cPLA2α plays a key role in the development of CIA, we backcrossed cPLA2α-deficient mice on the DBA/1LacJ background that is susceptible to CIA. The disease severity scores and the incidence of disease were markedly reduced in cPLA2α-deficient mice compared with wild-type littermates. At completion of the study, &amp;gt;90% of the wild-type mice had developed disease whereas none of the cPLA2α-deficient mice had more than one digit inflamed. Furthermore, visual disease scores correlated with severity of disease determined histologically. Pannus formation, articular fibrillation, and ankylosis were all dramatically reduced in the cPLA2α-deficient mice. Although the disease scores differed significantly between cPLA2α mutant and wild-type mice, anti-collagen antibody levels were similar in the wild-type mice and mutant littermates. These data demonstrate the critical role of cPLA2α in the pathogenesis of CIA.
Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial
Authors: Ernst-Rüdiger Kuse, Ploenchan Chetchotisakd, Clovis Arns da Cunha, Markus Ruhnke, Carlos Barrios, Digumarti Raghunadharao, Jagdev Singh Sekhon, Antonio Freire, Venkatasubramanian Ramasubramanian, Ignace Demeyer, Marcio Nucci, Amorn Leelarasamee, Frédérique Jacobs, Johan Decruyenaere, Didier Pittet, Andrew J Ullmann, Luis Ostrosky-Zeichner, Olivier Lortholary, Sonja Koblinger, Heike Diekmann-Berndt, Oliver A Cornely
Journal: The Lancet (2007)
Severe Lupus Nephritis
Authors: Stephen M. Korbet, Melvin M. Schwartz, Joni Evans, Edmund J. Lewis
Journal: Journal of the American Society of Nephrology (2006)

This study assessed whether certain clinicopathologic variables could explain the impact of race on outcome in 86 patients who had severe lupus nephritis and were available for long-term follow-up after participating in a prospective, controlled, clinical trial. Fifty-four (63%) patients were white, 21 (24%) were black, and 11 (13%) were categorized as other. The proportion of patients with anti-Ro, anti-nRNP, and anti-Sm was significantly greater among black patients. Biopsies with segmental active proliferative and necrotizing lesions that involved ≥50% of glomeruli ± membranous glomerulonephritis (class III ≥50%±V) were significantly more common (white 44%, black 76%, other 36%; P < 0.05) and diffuse proliferative glomerulonephritis ± membranous glomerulonephritis (class IV±V) was less common (white 54%, black 24%, other 64%) among black patients. Attainment of a remission was greatest among white patients (white 52%, black 29%, other 27%; P = 0.09). Features that were predictive of a remission were white race, baseline serum creatinine, and class IV±V lesions. Patient survival at 10 yr (white 81%, black 59%, other 73%; P = 0.029) and renal survival at 10 yr (white 68%, black 38%, other 61%; P = 0.015) were significantly poorer in black patients. Predictors of ESRD were serum creatinine, the presence of anti-Ro antibodies, class III ≥50%±V lesions, and failure to achieve a remission. In conclusion, racial differences were observed in the serologic and histologic features at presentation, response to treatment, and outcome of patients with severe lupus nephritis. In a population of patients with severe lupus nephritis, black patients were significantly more likely to have a serologic profile and renal lesions that were associated with more aggressive renal disease and resulted in worse outcomes than white patients.
Clonal Relationship of Classical Hodgkin Lymphoma and Its Recurrences
Authors: Ellen C. Obermann, Nadine Mueller, Alexander Rufle, Thomas Menter, Esther Mueller-Garamvoelgyi, Gieri Cathomas, Stephan Dirnhofer, Alexandar Tzankov
Journal: Clinical Cancer Research (2011)

We investigated whether the first and all subsequent manifestations of Hodgkin lymphoma (HL) in a patient are clonally related.We identified a collective of 20 patients with sometimes multiple HL recurrences. Relapses were classified as early, that is, within twelve months (eight events in seven patients) or as late, that is, later than one year after the previous neoplasm (24 events in 17 patients). Hodgkin and Reed-Sternberg cells were microdissected after CD30 staining using laser capture technique. Immunoglobulin heavy chain (IgH) gene fragment lengths were analyzed after DNA preamplification, applying consensus FR3 and J primers by ABI 310 Genetic Analyzer. Sequencing of the amplified IgH products was carried out by ABI 3130 and 3730XL Genetic Analyzer. Epstein-Barr virus (EBV) association was assessed by EBV early RNA and LMP1.Three cases with early relapses after a first HL diagnosis were clonally related to the initial tumor, whereas three of four patients with early relapses after a first or second relapse were not, which was accompanied by change of EBV association in one case. Six patients presenting with late relapses were clonally unrelated, which was accompanied by change of phenotype in two cases and change of EBV association in one case. Two samples from recurrent tumors of the same patient could be successfully sequenced. These two late relapses were clonally unrelated by IgH fragment length and sequencing analysis.Recurrent HL, especially those accompanied by an EBV-association switch or after a relapse, can represent an unrelated novel neoplasm. Our finding might play a role in clinical decision making.
How building physical models can reduce and guide the abstraction of nature
Authors: Malcolm A. MacIver
Journal: Behavioral and Brain Sciences (2001)

Animals detect and acquire resources through a sequence of shape changes. This process is tightly coupled to the sensory and mechanical ecology of the animal. Building physical models allow us to prescind from modeling these aspects of the environment, which may not yet be described or suitably abstracted. The significance of this hybrid of physical modeling and experimentation to the acquisition of scientific knowledge is discussed.
Lipoprotein Transport Gene Abnormalities Underlying Coronary Heart Disease Susceptibility
Authors: J L Breslow
Journal: Annual Review of Medicine (1991)

There is a close association between lipoprotein abnormalities and coronary heart disease susceptibility. Since 1982, the genes for the lipoprotein transport proteins have been isolated and at least partially characterized. Mutations in these genes are now being defined that underlie the common abnormalities found in heart attack victims. This review presents our current state of knowledge on this subject.
Could a sugar tax help combat obesity?
Authors: Sirpa Sarlio-Lähteenkorva, J T Winkler
Journal: BMJ (2015)

<b>Sirpa Sarlio-Lähteenkorva</b> says that a specific tax on sugar would reduce consumption, but <b>Jack Winkler</b> thinks that such taxes are politically unpalatable and would have to be enormous to have any effect
A double‐blind study of hyposensitization with an alginate‐ conjugated extract of <i>Dermatophagoides pteronyssinus</i> (Conjuvac®) in patients with perennial rhinitis
Authors: E. A. Pastorello, C. Ortolani, C. Incorvaia, L. Farioli, M. Italia, V. Pravettoni, R. J. Harris, H. K. Watson, O. J. Corrado, R. J. Davies, C. Zanussi
Journal: Allergy (1990)

In a 2-year double-blind placebo controlled study an immunological evaluation was carried out on 33 patients (15 males, 18 females, mean age 29.2 years) with mite-induced perennial rhinitis who were submitted to specific immunotherapy (IT) with an alginate-conjugated extract of D. pteronyssinus. The behaviour of IgE, IgG, IgG1 and IgG4 antibodies specific to D. pteronyssinus and its major allergen Der p1 was characterized by assessment of their changes in serum, and changes in IgG in nasal secretions during the treatment. The placebo-treated patients did not show any significant variation in the levels of specific antibodies, while in the actively treated patients we found: a statistically significant decrease (P less than 0.005) of specific IgE, a statistically significant increase of specific IgG (P less than 0.005), IgG1 (P less than 0.005) and IgG4 (P less than 0.005) in serum and a statistically significant increase (P less than 0.001) of specific IgG in nasal secretions. The IgG response showed an early relative predominance of the IgG1 subclass and a late absolute predominance of IgG4 subclass, that confirmed the model of IgG4 restriction in prolonged allergen stimulation. No correlation was found between immunological and clinical data.
Religion's evolutionary landscape needs pruning with Ockham's razor
Authors: William A. Rottschaefer
Journal: Behavioral and Brain Sciences (2004)

Atran &amp; Norenzayan (A&amp;N) have not adequately supported the epistemic component of their proposal, namely, that God does not exist. A weaker, more probable hypothesis, not requiring that component – that the benefits of religious belief outweigh those of disbelief, even though we do not know whether or not God exists – is available. I counsel them to use Ockham's razor, eliminate their negative epistemic thesis, and accept the weaker hypothesis.