tbuckley/cabot-search huggingface dataset:
Abstract 5053: Sonic hedgehog inhibition reduces <i>in vitro</i> tumorigenesis and alters expression of GLI1-target genes in a desmoplastic medulloblastoma cell line.
Authors: R Garcia-Lopez, B Vera-Cano, A Vacas-Oleas, J de la Rosa, G Gallo-Oller, M H. Shahi, X Fan, M M. Alonso, J A. Rey, Javier S. Castresana
Journal: Cancer Research (2013)

Abstract Medulloblastoma is one of the most frequent and aggressive tumors of childhood. The Sonic hedgehog (Shh) pathway, related to human development, is altered in most medulloblastomas: genes like Ptch, Smo, or Sufu suffer mutations in 15% to 25% of these tumors. We tested Shh inhibition in the Daoy medulloblastoma cell line by two methods: a molecular one (direct Gli1 siRNA inhibition); and a pharmacological inhibition of Smo, upstream of Gli1, by cyclopamine. Afterwards, a comparison of cellular and molecular responses was done. We proved that MTT cell viability, and cell migration assessed by the scratching assay decreased after Shh inhibition. Furthermore, colony formation assay in culture decreased by 70%, and colony formation assay in soft agar decreased up to 90% when Shh inhibition was applied. As a whole, Shh inhibition conferred a less in vitro tumorigenic status to Daoy cells. Moreover, we assessed the expression of different Gli1 target genes and other genes, before and after Shh inhibition, and found that Shh shows a crosstalk with oncogenes and tumor suppressor genes that have been described in numerous tumors. Therefore, we found downregulation of Ptch1, Cyclin D2, Plakoglobin, Nkx2.2, Bmi1, Smo and N-myc after Shh inhibition. Sufu and Gli3 showed parallel results, where Gli1 siRNA did neither decrease nor increase expression of both genes, whereas cyclopamine reduced them in 15-25%. Pax6 mRNA levels were upregulated by either Gli1 siRNA or cyclopamine. Finally, Notch1 was upregulated after inhibition of Shh, while Notch2 showed contrasting results, as siRNA inhibition decreased its expression, while cyclopamine increased it. All these experiments give an overview of the Shh pathway in medulloblastoma, its relationship with other genes, and the demonstration of the efficacy of cyclopamine and Gli 1 siRNA Shh inhibition in vitro. Citation Format: R Garcia-Lopez, B Vera-Cano, A Vacas-Oleas, J de la Rosa, G Gallo-Oller, M H. Shahi, X Fan, M M. Alonso, J A. Rey, Javier S. Castresana. Sonic hedgehog inhibition reduces in vitro tumorigenesis and alters expression of GLI1-target genes in a desmoplastic medulloblastoma cell line. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5053. doi:10.1158/1538-7445.AM2013-5053
P86Epac1-induced cardiac hypertrophy triggers autophagy
Authors: MB Bisserier, AL Laurent, FT Tortosa, AL Lucas, CH Heymes, CV Vindis, FL Lezoualc′h
Journal: Cardiovascular Research (2014)

Purpose: Although cAMP is one of the most well-known signaling molecules produced by β-adrenergic receptors (β-AR) stimulation, its mechanism of action in cardiac hypertrophy is not fully understood. Here, we investigated the involvement of the cAMP sensor Epac1 in β-AR-induced cardiac remodeling using knock-out mice for Epac1 (Epac1-/-) and cardiotropic adeno-associated viruses encoding Epac1 (AAV9-Epac1).
Coffee consumption, RF, and the risk of RA
Authors: J H GLASER
Journal: Annals of the Rheumatic Diseases (2000)

The incidence and risk of asthma among female cleaners employed in different industries was explored. An increased risk of asthma has been associated with the cleaning profession, in some but not all studies. All Finnish females employed as cleaners and all those employed in administrative work were followed for asthma incidence through a record linkage in 1986–1998. An individual was defined as an “incident case of asthma” if they received rights for special reimbursement of asthma medication from the national health insurance or were recognized as having occupational asthma. Age-adjusted relative risks (RR) were estimated for cleaners in comparison with those employed in administrative work. There were 2,414 and 5,235 cases of asthma among the cleaners and administrative workers, respectively. The RR was 1.50 (95% confidence interval (CI) 1.43–1.57) in cleaners. The risk was increased in cleaners working in nearly all major sectors of economic activity, but cleaners employed by companies concerned with the manufacture of basic metals (RR 2.47; 95% CI 1.68–3.64) and food products (RR 2.19; 95% CI 1.69–2.85) had the highest risk. Only 25 of the “cases of asthma” among cleaners had been recognized as being occupational asthma. It could be concluded that cleaners have an increased risk of persistent adult-onset asthma. Factors inherent to the environment where cleaning is performed or differences in the cleaning agents used may explain the observed differences between industries.
<i>Aurora A</i>Is a Repressed Effector Target of the Chromatin Remodeling Protein INI1/hSNF5 Required for Rhabdoid Tumor Cell Survival
Authors: SeungJae Lee, Velasco Cimica, Nandini Ramachandra, David Zagzag, Ganjam V. Kalpana
Journal: Cancer Research (2011)

Rhabdoid tumors (RT) are aggressive pediatric malignancies with poor prognosis. INI1/hSNF5 is a component of the chromatin remodeling SWI/SNF complex and a tumor suppressor deleted in RT. Previous microarray studies indicated that reintroduction of INI1/hSNF5 into RT cells leads to repression of a high degree of mitotic genes including Aurora Kinase A (Aurora A, STK6). Here, we found that INI1/SNF5 represses Aurora A transcription in a cell-type-specific manner. INI1-mediated repression was observed in RT and normal cells but not in non-RT cell lines. Chromatin immunoprecipitation (ChIP) assay indicated that INI1/hSNF5 associates with Aurora A promoter in RT and normal cells but not in non-RT cells. Real-time PCR and immunohistochemical analyses of primary human and mouse RTs harboring mutations in INI1/hSNF5 gene indicated that Aurora A was overexpressed/derepressed in these tumor cells, confirming that INI1/hSNF5 represses Aurora A in vivo. Knockdown of Aurora A impaired cell growth, induced mitotic arrest and aberrant nuclear division leading to decreased survival, and increased cell death and caspase 3/7-mediated apoptosis in RT cells (but not in normal cells). These results indicated that Aurora A is a direct downstream target of INI1/hSNF5-mediated repression in RT cells and that loss of INI1/hSNF5 leads to aberrant overexpression of Aurora A in these tumors, which is required for their survival. We propose that a high degree of Aurora A expression may play a role in aggressive behavior of RTs and that targeting expression or activity of this gene is a novel therapeutic strategy for these tumors.
Anaemia in a 17 year old student
Authors: A-R Abu-Sitta, H. R Dalton
Journal: BMJ (2008)

A 17 year old non-vegetarian Asian female student presented with a three year history of increasing lethargy and shortness of breath during exercise. On examination she was clinically anaemic but had no other physical signs.

Haematological investigations, including a blood film (fig 1⇓), were performed. Her haemoglobin was 85 g/l (normal range 120-160 g/l), mean cell volume was 79 fl (80-96 fl), mean cell haemoglobin was 25 pg (27.3-32.6 pg), haematocrit was 29% (0.36%-0.44%), white blood cell count was 5.0×109/l (4-11×109/l), differential cell count was normal, and platelets were 550×109/l (150-400×109/l).



Fig 1 The patient’s blood film





### Short answers



Fig 2 The patient’s blood film showing microcytosis (red arrow), hypochromia (green arrow), and pencil cells (black arrow)



### Long answers

#### 1. Abnormalities

The blood film (fig 2⇑) showed microcytosis, hypochromia, and pencil cells. Microcytes (red arrow) have normal morphology but are smaller than normal red blood cells. By definition the volume of a microcyte does not exceed 80 fl (the lower limit of normal mean cell volume). When looking at a blood film, a normal sized red cell should be about the same …
Nearly 50 000 adults in the United Kingdom now have HIV
Authors: S. Pincock
Journal: BMJ (2003)

The number of people infected with HIV in the United Kingdom increased by almost 20% between 2001 and 2002, from 41 700 to 49 500, says a report published by the Health Protection Agency to mark world AIDS day, 1 December.

Also, the proportion of people who acquire their infection in the United Kingdom, as opposed to overseas, is increasing, the report says.

Kevin Fenton, a public health consultant on HIV at the agency, said, “World …
New cervical smear test could improve screening accuracy
Authors: R. Woodman
Journal: BMJ (1998)

A new cervical cancer smear test, which promises to save thousands of lives by reducing the potential for human error in identifying abnormal cervical cells, has successfully completed early stage trials and could be launched within three years, researchers in the United Kingdom announced this week.

The test, developed by Cancer Research Campaign (CRC) scientists at Cambridge University, uses antibodies that home in on Cdc6 and Mcm5, two recently discovered protein molecules that regulate DNA replication and are only present in cells which have the potential to replicate. A green fluorescent or brown dye is used to highlight these antibodies so that any abnormal cells stand out much more clearly than …
Synergistic effect of storage pool deficient platelets and low plasma von willebrand factor on the severity of the hemorrhagic diathesis in hermansky‐pudlak syndrome
Authors: Carl J. Witkop, E. J. Walter Bowie, Marlys D. Krumwiede, Jane L. Swanson, Elizabeth A. Plumhoff, James G. White
Journal: American Journal of Hematology (1993)

Abstract A study of 565 Puerto Rican patients with storage pool deficient (SPD) Hermansky‐Pudlak syndrome (HPS) demonstrated that most HPS patients had minor bleeding episodes while others had repeated, severe hemorrhagic episodes requiring transfusion. The severity of bleeding in these latter patients could not be attributed to their SPD alone. As swine with SPD platelets and low von Willebrand factor antigen (vWF:Ag) have more severe hemorrhages than pigs with either defect alone, 146 albino patients and 46 normally pigmented patients were examined for their level of vWF:Ag. The risk of SPD HPS patients having severe, repeated bleeding episodes increased when vWF:Ag fell below 70 U/dL. Family studies indicated that low vWF:Ag levels were more frequently associated with O blood group than from a gene suppressing production or release of vWF1. HPS patients should be tested for vWF:Ag levels. © 1993 Wiley‐Liss, Inc.
Safety and Efficacy of Normalizing Fasting Glucose With Bedtime NPH Insulin Alone in NIDDM
Authors: Kenneth Cusi, Glenn R Cunningham, John P Comstock
Journal: Diabetes Care (1995)

OBJECTIVE To examine the safety and overall clinical effects of normalizing the fasting plasma glucose (FPG) level with bedtime NPH insulin alone in patients with non-insulin-dependent diabetes mellitus (NIDDM) that is poorly controlled with maximal doses of sulfonylureas. RESEARCH DESIGN AND METHODS Twelve obese male NIDDM subjects were treated for 16 weeks with bedtime insulin after a 4-week sulfonylurea washout. The insulin dosage was increased until the FPG level was normalized. The 24-h plasma glucose profiles and lipid and HbA1c levels were measured at the beginning and end of the study, and the incidence and severity of hypoglycemic episodes were closely monitored. In addition, hyperglycemic clamp studies were performed to assess insulin secretion and provide an indirect measurement of insulin sensitivity. RESULTS FPG (14.6 ± 0.9 mmol/l at week 0) was normalized (&amp;lt;6.4 mmol/l) within 6 weeks (5.9 ± 0.6 mmol/l) and remained at target levels until the end of the study (4.0 ± 0.03 mmol/l at week 16, P &amp;lt; 0.001). The insulin dose was 80 ± 9 U/day (0.86 ± 0.10 U/kg). Improved glycemic control was confirmed by a reduction in HbA1c (10.9 ± 0.05 vs. 7.2 ± 0.2%, P &amp;lt; 0.001) and mean 24-h glucose (17.2 ± 0.2 vs. 7.4 ± 0.2 mmol/l, P &amp;lt; 0.001). The incidence of mild or moderate hypoglycemic episodes was 3.4 ± 1/patient for the entire 16-week study, and no patient experienced severe hypoglycemia. Bedtime insulin significantly improved total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglyceride levels (P &amp;lt; 0.01). Weight gain was 2.4 ± 0.7 kg, and blood pressure was unchanged. During the hyperglycemic clamp, there was an improvement in the first phase (P &amp;lt; 0.001) and in the second phase (P &amp;lt; 0.01) of insulin secretion. There also was an increase in the rate of exogenous glucose infused (M)(P &amp;lt; 0.01) and in the M/C-peptide ratio (P &amp;lt; 0.02), suggesting enhanced insulin sensitivity. CONCLUSIONS NPH insulin given at bedtime in amounts sufficient to achieve a normal FPG level does not cause excessive or severe hypoglycemia and does lead to good glycemic and lipid control in NIDDM. Bedtime insulin therapy also is accompanied by improved insulin secretion and insulin sensitivity. We conclude that a single dose of insulin alone at bedtime merits consideration as a therapeutic strategy in patients with poorly controlled NIDDM.
Dopamine and extraversion: Differential responsivity may be the key
Authors: Thomas H. Rammsayer
Journal: Behavioral and Brain Sciences (1999)

Depue &amp; Collins's general idea of a functional relationship between DA activity and extraversion is an important step toward an integrative biological model of personality. However, focusing primarily on incentive motivation and variations in VTA DA activity as basic behavioral and biological components underlying extraversion appears too limited. Existing data suggest that responsivity to changes in DA activity is higher in introverts than in extraverts. This may reflect a general, extraversion- related characteristic of the entire dopaminergic network in the brain.
TREATMENT OF NERVOUS INDIGESTION
Authors: WALTER C. ALVAREZ
Journal: JAMA (1927)

Having in mind that ancient recipe for rabbit stew which begins with the injunction, "first catch your rabbit," I begin this paper with the suggestion that you first be sure of your patient's neurosis before you begin to treat him for it; be sure that he is not suffering from something else besides nerves. When one sees how often the skilled gastro-enterologist with every form of technical assistance at his command makes the mistake of treating as a "neurotic" some one who has gallstones, tumor of the cord, incipient tuberculosis, or cancer of the stomach, the need for caution becomes obvious. If only, then, because we may be mistaken, we should be particularly careful to avoid conveying to our patients the impression that we think there is nothing the matter with them. They may be neurotic, hypersensitive and overcomplaining, but that does not render them immune to organic disease. In
The Antimicrobial Protein REG3A Regulates Keratinocyte Proliferation and Differentiation after Skin Injury
Authors: Yuping Lai, Dongqing Li, Changwei Li, Beda Muehleisen, Katherine A. Radek, Hyun Jeong Park, Ziwei Jiang, Zhiheng Li, Hu Lei, Yanchun Quan, Tian Zhang, Yelin Wu, Paul Kotol, Shin Morizane, Tissa R. Hata, Keiji Iwatsuki, Ce Tang, Richard L. Gallo
Journal: Immunity (2012)
Stroke mortality declines; still major health problemm
Authors: Phil Gunby
Journal: JAMA (1984)

Although cerebrovascular disease remains a major health problem in the United States and elsewhere, "the death rate from stroke declined by 46% from 1968 to 1981," an American Heart Association (AHA) official—Edward S. Cooper, MD—points out. Cooper, who is professor of medicine, University of Pennsylvania School of Medicine, Philadelphia, is chair of the AHA's Stroke Council. He noted during the AHA's annual scientific sessions in Anaheim, Calif, that "the rate of death from all diseases in the United States dropped by only 13%" while a larger decline in stroke-related deaths was being documented. And, says a researcher at the Center for Demographic Studies, Duke University, Durham, NC, "recent data suggest that this trend [the declining mortality rate associated with stroke] is continuing." Kenneth G. Manton, PhD, an associate research professor at the center, has been working with the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS), Bethesda, Md,
Familial risk of cerebral palsy: population based cohort study
Authors: M. C. Tollanes, A. J. Wilcox, R. T. Lie, D. Moster
Journal: BMJ (2014)

<b>Objective</b> To investigate risks of recurrence of cerebral palsy in family members with various degrees of relatedness to elucidate patterns of hereditability. <b>Design</b> Population based cohort study. <b>Setting</b> Data from the Medical Birth Registry of Norway, linked to the Norwegian social insurance scheme to identify cases of cerebral palsy and to databases of Statistics Norway to identify relatives. <b>Participants</b> 2 036 741 Norwegians born during 1967-2002, 3649 of whom had a diagnosis of cerebral palsy; 22 558 pairs of twins, 1 851 144 pairs of first degree relatives, 1 699 856 pairs of second degree relatives, and 5 165 968 pairs of third degree relatives were identified. <b>Main outcome measure</b> Cerebral palsy. <b>Results</b> If one twin had cerebral palsy, the relative risk of recurrence of cerebral palsy was 15.6 (95% confidence interval 9.8 to 25) in the other twin. In families with an affected singleton child, risk was increased 9.2 (6.4 to 13)-fold in a subsequent full sibling and 3.0 (1.1 to 8.6)-fold in a half sibling. Affected parents were also at increased risk of having an affected child (6.5 (1.6 to 26)-fold). No evidence was found of differential transmission through mothers or fathers, although the study had limited power to detect such differences. For people with an affected first cousin, only weak evidence existed for an increased risk (1.5 (0.9 to 2.7)-fold). Risks in siblings or cousins were independent of sex of the index case. After exclusion of preterm births (an important risk factor for cerebral palsy), familial risks remained and were often stronger. <b>Conclusions</b> People born into families in which someone already has cerebral palsy are themselves at elevated risk, depending on their degree of relatedness. Elevated risk may extend even to third degree relatives (first cousins). The patterns of risk suggest multifactorial inheritance, in which multiple genes interact with each other and with environmental factors. These data offer additional evidence that the underlying causes of cerebral palsy extend beyond the clinical management of delivery.
Ultrastructural binding sites of endomysium antibodies from sera of patients with dermatitis herpetiformis and coeliac disease.
Authors: S Karpati, M Meurer, W Stolz, A Burgin-Wolff, O Braun-Falco, T Krieg
Journal: Gut (1992)

The ultrastructural binding sites of endomysium antibodies, specific serological markers of gluten sensitive enteropathy, were investigated in the rabbit oesophagus using the immunogold technique. Endomysium antibodies from sera of patients with dermatitis herpetiformis and with coeliac disease bound in an identical manner in a non-fibrillar material closely associated with fine collagenous-reticulin fibrils and also with similar fibrils connecting smooth muscle cells and elastic tissue in the endomysial connective tissue. These observations suggest that IgA antibodies in sera from patients with dermatitis herpetiformis and coeliac disease recognise a common antigen in an amorphous component associated with the reticular connective tissue of oesophageal lamina muscularis mucosae and thus confirm the probable identity of IgA class endomysium and jejunal antibodies.
Dr Webb of Colorado Springs
Authors: Thomas L. Petty
Journal: JAMA (1985)

The history of the treatment of tuberculosis is one of the most fascinating stories in modern medicine. Today we take moderate short-course chemotherapy for granted and are confident that cure can be achieved in nearly 100% of the patients who take two or three oral medications for approximately nine months, assuming their infective organisms are susceptible. How different it was at the turn of this century when tuberculosis was the most common cause of death in the United States and throughout Europe! The progress that has reduced tuberculosis to a relatively minor health problem in the United States today (but with some notable exceptions in certain areas of the country) has been the product of the collaboration of many persons and associations trying to find the most efficient means of treating tuberculosis. (By contrast, tuberculosis remains essentially unchallenged as a worldwide health problem.) Gerald Bertram Webb is one of those
Oral Contraceptives — Time to Take Stock
Authors: Samuel Shapiro
Journal: New England Journal of Medicine (1986)

About 1 in 13 women in the United States can expect to have breast cancer, and there is abundant evidence to suggest a hormonal component in its causation.1 Not surprisingly, therefore, the widespread use of oral contraceptives has been a source of continuing concern since they were introduced in the early 1960s — a concern heightened by our knowledge that hormonally related factors, such as age at first pregnancy, can continue to influence the risk of breast cancer for an entire lifetime. In this issue of the Journal, the findings of the Cancer and Steroid Hormone Study provide welcome . . .
Abnormal Nerve Conduction in Impotent Patients With Diabetes Mellitus
Authors: John S Daniels
Journal: Diabetes Care (1989)

The etiology of impotence in the diabetic population has not been clearly defined. To assess this problem, 24 impotent diabetic subjects, 21 nonimpotent diabetic subjects, and 10 subjects with psychogenic impotence were compared with nocturnal monitoring of penile tumescence and rigidity, penile arterial blood flow, and nerve conduction of the pudendal nerve. There was no statistical difference in mean age or duration of diabetes among the various study groups. All diabetic subjects who presented with complaints of impotence had severe abnormalities on nocturnal erection monitoring. There was no significant difference in the mean penile brachial index between impotent and nonimpotent diabetic subjects (P = .335). In contrast, there was a significant difference in bulbocavernosus-reflex latency times (P less than .001) between impotent (mean latency 48.4 ms) and nonimpotent (mean latency 38.7 ms) diabetic subjects. This study strongly suggests that impotence in the diabetic population is secondary to functional abnormalities of pelvic nerves and that the bulbocavernosus-reflex latency time is an excellent diagnostic test for assessing function of pelvic nerves in the diabetic individual.