tbuckley/cabot-search huggingface dataset:
Fatty Liver and Fibrosis in Glycine N -Methyltransferase Knockout Mice Is Prevented by Nicotinamide
Authors: Marta Varela-Rey, Nuria Martínez-López, David Fernández-Ramos, Nieves Embade, Diego F. Calvisi, Aswhin Woodhoo, Juan Rodríguez, Mario F. Fraga, Josep Julve, Elisabeth Rodríguez-Millán, Itziar Frades, Luís Torres, Zigmund Luka, Conrad Wagner, Manel Esteller, Shelly C. Lu, Luz M. Martínez-Chantar, José M. Mato
Journal: Hepatology (2010)

Deletion of glycine N-methyltransferase (GNMT), the main gene involved in liver S-adenosylmethionine (SAM) catabolism, leads to the hepatic accumulation of this molecule and the development of fatty liver and fibrosis in mice. To demonstrate that the excess of hepatic SAM is the main agent contributing to liver disease in GNMT knockout (KO) mice, we treated 1.5-month-old GNMT-KO mice for 6 weeks with nicotinamide (NAM), a substrate of the enzyme NAM N-methyltransferase. NAM administration markedly reduced hepatic SAM content, prevented DNA hypermethylation, and normalized the expression of critical genes involved in fatty acid metabolism, oxidative stress, inflammation, cell proliferation, and apoptosis. More importantly, NAM treatment prevented the development of fatty liver and fibrosis in GNMT-KO mice. Because GNMT expression is down-regulated in patients with cirrhosis, and because some subjects with GNMT mutations have spontaneous liver disease, the clinical implications of the present findings are obvious, at least with respect to these latter individuals. Because NAM has been used for many years to treat a broad spectrum of diseases (including pellagra and diabetes) without significant side effects, it should be considered in subjects with GNMT mutations. The findings of this study indicate that the anomalous accumulation of SAM in GNMT-KO mice can be corrected by NAM treatment leading to the normalization of the expression of many genes involved in fatty acid metabolism, oxidative stress, inflammation, cell proliferation, and apoptosis, as well as reversion of the appearance of the pathologic phenotype.
PI3K/p110δ is a novel therapeutic target in multiple myeloma
Authors: Hiroshi Ikeda, Teru Hideshima, Mariateresa Fulciniti, Giulia Perrone, Naoya Miura, Hiroshi Yasui, Yutaka Okawa, Tanyel Kiziltepe, Loredana Santo, Sonia Vallet, Diana Cristea, Elisabetta Calabrese, Gullu Gorgun, Noopur S. Raje, Paul Richardson, Nikhil C. Munshi, Brian J. Lannutti, Kamal D. Puri, Neill A. Giese, Kenneth C. Anderson
Journal: Blood (2010)
Screening for cystic fibrosis. Specialists get on with it.
Authors: M Super, G Malone, M J Schwarz, A Howarth, T Roberts
Journal: BMJ (1993)

know which recessive genes they carry"?Current evidence from a general practice population of reproductive age shows that "there is not a great deal of demand or interest in cystic fibrosis carrier testing" and that "such testing is not really wanted."2An editorial on the same subject in the Lancet concluded that "we need to think very carefully about whether nationwide programmes are what we really want and what the aims and ethical base of such an approach may be."3Before further research is carried out a national commission with representative membership needs to consider all the implications of screening the general population for cystic fibrosis and whether the potential benefits to society truly outweigh all the costs.
Local Service Growth: The Illinois Zone Plan
Authors: NORRIS HANSELL, DONALD W. HART
Journal: American Journal of Psychiatry (1970)

The authors describe an aspect of the Illinois Zone Plan, which is dependent upon substantial increases in local, noninstitutional, and private mental health services to achieve reductions in the use of institutional care under state auspices. Apparent headway has been made using a close linkage between state granting policy, new mental health laws, and consultation with newly established county-level mental health planning authorities.
US Senate doesn't repeal health reform, but states defy the act
Authors: J. H. Tanne
Journal: BMJ (2011)

The Democratic controlled US Senate voted on Wednesday 2 February not to repeal the health reform act passed last March. The Republican controlled House of Representatives had voted two weeks ago to repeal the act ( BMJ 2011;342:d441, 21 Jan, doi:10.1136/bmj.d441).

The Senate vote means that the repeal bill is dead for this Congress, but Republicans have said that they would continue efforts to repeal or defund parts of the bill.

In court decisions two judges have ruled that the health reform law is unconstitutional, and another two have ruled that it is constitutional. The case is …
Vitamin D Supplementation and Cardiovascular Disease Risk
Authors: Erin D. Michos, Roger S. Blumenthal
Journal: Circulation (2007)

any studies, 1,2 but not all, have shown that low bone density is associated with increased cardiovascular disease (CVD) risk.Vitamin D deficiency is common in the elderly and is associated with osteoporosis; however, the association of endogenous 25-OH vitamin D (25-OH D) levels with CVD events is controversial. 3,4CVD rates are higher during winter seasons and at increased geographic latitudes where average serum vitamin D levels are lowest. 5Low 25-OH D levels have been found in stroke 6 and heart failure patients. 7Moreover, 25-OH D deficiency is associated with hypertension, obesity, 8 glucose intolerance, 8 and the metabolic syndrome, 9 which may be responsible, at least in part, for its association with increased CVD risk.
New Editor at Archives of General Psychiatry
Authors: Phil Gunby
Journal: JAMA (1994)

WHEN THEY were fellow students at Yale University School of Medicine, Jack D. Barchas and Kenneth A. Arndt—both a continent away from their native California and both pondering which medical specialty to enter—exchanged books on dermatology and psychiatry, respectively. Whatever role those books played in their decisions in New Haven, Conn, each chose well and excelled. Arndt, professor of dermatology, Harvard Medical School, and dermatologistin-chief, Beth Israel Hospital, Boston, Mass, has been editor of the American Medical Association's<i>Archives of Dermatology</i>since 1984. <h3>Now Fellow Editors</h3> And now Barchas, the Barklie McKee Henry Professor and chair, Department of Psychiatry, Cornell University Medical College, and psychiatrist-in-chief, New York (NY) Hospital, has become editor of a sister American Medical Association monthly journal,<i>Archives of General Psychiatry</i>. He succeeds the late Daniel X. Freedman, MD, and is only the third editor in the journal's 35-year recent history. The journal actually is 75 years
A memorable patient: Medical care in the Raj
Authors: B. Dev
Journal: BMJ (1997)

Summer of 1945. Father had just been promoted to the rank of risaldar (junior commissioned officer) in the cavalry. Almost simultaneously, he had also been found on a barium study to have a gastric ulcer, the size of a Victorian rupee. He was promptly admitted to the Satwari cantonment hospital in Jammu. He was responding to medical …
Abstract 772: Targeted cancer therapy with immunotoxins
Authors: Merete T. Wiiger, Øystein Fodstad, Yvonne Andersson
Journal: Cancer Research (2011)

Abstract The therapeutic options for patients with metastasis are generally limited and the need to develop better treatment modalities is obvious. Immunotoxins (ITs) represent a promising group of targeted therapeutics, consisingt of a cancer-specific antibody and a cell killing toxin. The number of IT protocols approved for treatment of cancer patients is expected to increase, as this type of treatment has several advantages compared to conventional strategies. Unfortunately, the clinical use of ITs has been hampered by liver toxicity and the induction of a strong anti-IT-antibody response. However, in an ongoing clinical phase I study with one of our ITs, targeting EpCAM, in combination with the immunosuppressor cyclosporin (CsA) we have demonstrated only transient liver toxicity and minimal/no anti-IT antibody response. We are now investigating the potential use of our-clinical grade BM7PE for patients with triple-negative breast cancer (TNBC) and peritoneal carcinomatosis from ovarian cancer, for whom standard treatment is no longer an option. This IT targets Mucin-1 which is over-expressed and aberrantly glycosylated in these cancer types. We have found that the combination of BM7PE and CsA caused a remarkable synergistic effect in killing the TNBC cell lines MDAMB468 and MDAMB231, as well as in the ovarian cell line B76, established from pleural effusion. The mechanisms underlying this synergism in vitro have been thoroughly studied in cell viability assays, western blot and PCR-arrays. Preliminary data show reduced Matrigel invasion, which was even more inhibited by the combination with CsA. This suggests that the IT treatment does regulate cellular migration and invasion. Further investigations are ongoing to identify molecular pathways involved in IT- (+/-CsA) induced cell death and invasion. In conclusion, the combination of BM7PE and CsA might constitute an important improvement and increase the possible clinical potential of IT in these patient groups. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 772. doi:10.1158/1538-7445.AM2011-772
448 NOTCH 1 REGULATES FOXP3 REGULATORY T CELLS AND MAY CONTRIBUTE IN DERANGED TGF-β SIGNALING IN PROGRESSIVE STAGE OF HEPATITIS B INFECTED CIRRHOSIS
Authors: N. Trehanpati, S. Gupta, S. Shrivastav, D. Tripathy, S. Sukriti, S.K. Sarin
Journal: Journal of Hepatology (2010)
Emotion, and Rhythm of Breathing and Heart Beat
Authors: Hitoshi Ishikawa
Journal: Psychotherapy and Psychosomatics (1970)

The author analyzed changes in heart beat rhythm of the normal cases as well as the cases of cardiac neurosis and arteriosclerosis, using respiration curves and cardiotachographic recording. The heart beat rhythms are divided into three groups, the random effect, the cyclic effect and trend effect. The patterns of heart beat rhythm can be classified into three groups, namely; the normal type showing a moderate degree of respiratory arrythmia and the arteriosclerotic type respiratory arrythmia is not conscipcous, while the cases of cardiac neurosis belong either to the type a showing marked respiratory arrythmia or to the type b with shortened R-R interval showing no respiratory arrythmia.
Intractable headache after lumbar puncture
Authors: V. S. Noble, I. Davagnanam, S. Farmer
Journal: BMJ (2011)

A 17 year old man presented to the accident and emergency department with a severe headache, neck stiffness, fever, and photophobia. His blood tests showed neutrophylic leucocytosis and raised C reactive protein. A computed tomography scan of his brain was normal. Lumbar puncture detected 71 white blood cells (55% lymphocytes and 45% polymorphs) and was positive for enterovirus. A low cerebrospinal fluid (CSF) opening pressure was noted. His blood cultures also grew Streptococcus viridans . He was treated for viral meningitis and bacteraemia with intravenous aciclovir and antibiotics for two weeks, at which time he discharged himself. He presented again three weeks later with an intractable headache, which was reportedly aggravated by sitting up and standing; he also had back pain. His inflammatory markers at this time were normal. Magnetic resonance imaging of the brain and spine was performed (figs 1⇓ and 2⇓).



Fig 1 Coronal post-contrast T1 weighted magnetic resonance imaging of the brain 





Fig 2 Midline sagittal (a) T2 weighted and (b) T1 weighted magnetic resonance imaging of the cervical spine. (c) Post-contrast parasagittal T1 weighted magnetic resonance imaging of the cervical spine 





### 1 What are the radiological findings?

#### Short answer

Crowding and caudal displacement (“sagging”) of the posterior fossa structures of the brain (fig 3A and B⇓). Diffuse pachymeningeal enhancement (fig 4⇓), engorgement of the epidural venous plexuses (fig 3C). Thoracic epidural collection (fig 3A and C).



Fig 3 Midline sagittal (a) T2 weighted and (b) T1 weighted magnetic resonance imaging of the cervical spine showing crowding of structures in the foramen magnum (arrows). (c) Post-contrast parasagittal T1 weighted magnetic resonance …
FURTHER OBSERVATIONS ON THE REACTION OF BACILLUS PESTIS IN PLAGUE
Authors: R. Row
Journal: BMJ (1903)

On June 26th a normal guinea-pig of 260 grams weight was injected with ,the total broth emulsion obtained from six sloped agar tubes of "mild" typhoid and was alive and quite well on the 2gth.On June 28th another normal guinea-pig of 2 grams weight was in- jected with iI tubes of the " mild " typhoid emulsified In 6 c.cm. of broth.This animal died the same night; and post mortem in this as in all the -other cases of death from these injections the pathogenic micro-organism 'was recovered by cultures from the heart's blood and spleen pulp.It was consequently obvious that the minimum lethal dose of this mild typhoid for 300 grams of guinea-pig was therefore somewhere between six and eleven tubes; and hence estimating by tubes, as only half a tube of "I virulent " had the same effect, that the method adopted had resulted, on this basis, in at least a 12-fold increase of virulence.As enumerations of the typhoid bacilli in a given volume of a broth culture, according to the method described by Wright in the Lancet of June ist, I9oi, were being daily -carried out in the Netley laboratory, the opportunity was taken of thus enumerating the broth emulsions of typhoid bacilli administered to the guinea-pigs mentioned.Omitting the mass of figures involved in the calculation, which have been carefully verified, the results may be summed up as follows:June 14th.-182,0oomillions of " virulent" typhoid bacilli-the half of the product of one sloped agar tube-killed 330 grams of guinea-pig in forty-eight hours.June 14th.-280,000millions of " mild" typhoid bacilli-the product of two tubes-failed to kill 310 grams of guinea-pig.June 26th.-330,000millions of " mild "-the product of six tubes-failed to kill 260 grams of guinea-pig.June 28th.-552,000millions of " mild "-the product of eleven tubes- killed 255 grams of guinea-pig in fifteen hours.This enumeration method only takes count of living bacilli.
Chronic Membranous Glomerulonephritis Caused by Hepatitis B Antigen-Antibody Immune Complexes
Authors: Peter F. Kohler, Robert E. Cronin, William S. Hammond, David Olin, Ronald I. Carr
Journal: Annals of Internal Medicine (1974)

The immunopathogenesis of chronic membranous glomerulonephritis was investigated in a 42-year-old man with chronic active hepatitis, type B. In two renal biopsies, 14 months apart, immunofluorescent study showed glomerular deposition of the hepatitis B antigen (HB Ag) and host IgG IgM, and C3 in an irregular "immune complex" pattern. Electron microscopy showed dense deposits in the thickened basement membrane but no morphologic evidence of the intact, spherical, 20-nm HB Ag. Low concentrations of HB Ag were found in serial serum samples whereas total complement and component concentrations were normal. Most significantly, circulating HB Ag-antibody complexes were directly shown by serum cryoprecipitation. Results of in-vitro tests for a cell-mediated immune response to HB Ag were negative. The potential importance of chronic hepatitis B virus infection as a primary cause of human immune-complex glomerulonephritis is supported by our findings.
Oncogenic ERBB3 Mutations in Human Cancers
Authors: Bijay S. Jaiswal, Noelyn M. Kljavin, Eric W. Stawiski, Emily Chan, Chaitali Parikh, Steffen Durinck, Subhra Chaudhuri, Kanan Pujara, Joseph Guillory, Kyle A. Edgar, Vasantharajan Janakiraman, Rolf-Peter Scholz, Krista K. Bowman, Maria Lorenzo, Hong Li, Jiansheng Wu, Wenlin Yuan, Brock A. Peters, Zhengyan Kan, Jeremy Stinson, Michelle Mak, Zora Modrusan, Charles Eigenbrot, Ron Firestein, Howard M. Stern, Krishnaraj Rajalingam, Gabriele Schaefer, Mark A. Merchant, Mark X. Sliwkowski, Frederic J. de Sauvage, Somasekar Seshagiri
Journal: Cancer Cell (2013)
Lentiviral gene therapy of murine hematopoietic stem cells ameliorates the Pompe disease phenotype
Authors: Niek P. van Til, Merel Stok, Fatima S. F. Aerts Kaya, Monique C. de Waard, Elnaz Farahbakhshian, Trudi P. Visser, Marian A. Kroos, Edwin H. Jacobs, Monique A. Willart, Pascal van der Wegen, Bob J. Scholte, Bart N. Lambrecht, Dirk J. Duncker, Ans T. van der Ploeg, Arnold J. J. Reuser, Monique M. Verstegen, Gerard Wagemaker
Journal: Blood (2010)
The Cystic Fibrosis Gene: Medical and Social Implications for Heterozygote Detection
Authors: Benjamin S. Wilfond
Journal: JAMA (1990)

The primary goal of mass screening programs for cystic fibrosis carriers should be to allow people to make more informed reproductive decisions. However, previous experience with genetic screening programs, including those for phenylketonuria and sickle cell disease, have revealed complex problems including error, confusion, and stigmatization. These problems could be greater with cystic fibrosis, since more than 8 million Americans may be carriers and entrepreneurial interests can be expected to promote screening in what could become a billion-dollar industry. The present frequency of the detectable mutation (ΔF<sub>508</sub>), 75%, will complicate the counseling process. The sensitivity of the test to detect at-risk couples would be 56%. The cost of screening could be as much as $2.2 million for each cystic fibrosis birth avoided. Regardless of improvements in the detection rate, implementation of population screening should be delayed until pilot studies that demonstrate its safety and effectiveness are completed. While studies are in progress, preconception testing should be offered to adult relatives of cystic fibrosis patients as part of a comprehensive program following institutional review board approval for "compassionate use." The purpose of such review should be to ensure that strict standards of informed consent, education, quality control of the testing procedure, and counseling are followed. Primary care physicians who are unable to offer screening as part of such a comprehensive program should refer high-risk patients who would like to consider being tested to established centers. (<i>JAMA</i>. 1990;263:2777-2783)
P21 Nasal absorption of an ACTH(4–9) peptide analogue and its effect on peripheral nerve regeneration in rats
Authors: N.G.M. Schipper, J. Verhoef, S.G. Romeijn, J.H. Brakkee, V.M. Wiegant, W.H. Gispen, F.W.H.M. Merkus
Journal: Journal of Controlled Release (1994)
Ab initio molecular dynamics simulations of structural changes associated with the incorporation of fluorine in bioactive phosphate glasses
Authors: Jamieson K. Christie, Richard I. Ainsworth, Nora H. de Leeuw
Journal: Biomaterials (2014)

Phosphate-based bioactive glasses containing fluoride ions offer the potential of a biomaterial which combines the bioactive properties of the phosphate glass and the protection from dental caries by fluoride. We conduct accurate first-principles molecular dynamics simulations of two compositions of fluorinated phosphate-based glass to assess its suitability as a biomaterial. There is a substantial amount of F-P bonding and as a result the glass network will be structurally homogeneous on medium-range length scales, without the inhomogeneities which reduce the bioactivity of other fluorinated bioactive glasses. We observe a decrease in the network connectivity with increasing F content, caused by the replacement of bridging oxygen atoms by non-bridging fluorine atoms, but this decrease is small and can be opposed by an increase in the phosphate content. We conclude that the structural changes caused by the incorporation of fluoride into phosphate-based glasses will not adversely affect their bioactivity, suggesting that fluorinated phosphate glasses offer a superior alternative to their silicate-based counterparts.
GPs spot 80% of cancers within two consultations, audit shows
Authors: S. Mayor
Journal: BMJ (2013)

GPs refer more than three quarters of people who go on to receive a diagnosis of cancer after only one or two consultations, shows an audit of cancer diagnosis in England. The audit concludes that the number of consultations is a useful indicator of the time interval between a patient presenting with cancer symptoms and being referred to see a specialist.1

But the results show that GPs have more consultations with patients who have cancers with non-specific symptoms, including multiple myeloma and stomach and lung cancer, typically seeing them at least three times before referring them to a specialist.

The …
Africa is ill equipped to fight a bird flu epidemic
Authors: Peter Moszynski
Journal: BMJ (2006)

The emergence of the H5N1 strain of avian influenza in several countries in Europe and Africa last week has led the World Health Organization to issue a warning. It said: “H5N1 is spreading rapidly across the world. All countries must take measures to protect human health against avian flu, and prepare for a pandemic.”

H5N1 has now been identified in migratory swans in Italy, Greece, and Slovenia, but it is the arrival of the virus in …
Safety in Transfusion Practices
Authors: George D. Wilner
Journal: JAMA (1983)

This monograph summarizes the proceedings of the 1980 Aspen Conference, sponsored by the Blood Bank Resource Committee of the College of American Pathologists. The intent of the conference was to discuss three critical aspects of transfusion safety: transmission of disease, pretransfusion testing, and adverse effects of transfusion.  The monograph is divided into five parts. Part 1 deals with diseases transmitted by transfusion, and mainly includes discussions about posttransfusion hepatitis in relation to epidemiology and in vitro screening. Parts 2 and 3 are concerned with the adequacy of existing methods and procedures used in current bloodcompatibility testing. Here, the discussants correctly advocate using type and screen procedures and eliminating the requisite saline roomtemperature incubation phase of the standard cross-matching procedure, -as a means of improving the effectiveness of transfusion services. The remaining two sections are more clinically oriented, discussing the advantages of washed RBCs in prevention of transfusion reactions and concluding