tbuckley/cabot-search huggingface dataset:
Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome
Authors: Yuan Tian, Irina Voineagu, Sergiu P Paşca, Hyejung Won, Vijayendran Chandran, Steve Horvath, Ricardo E Dolmetsch, Daniel H Geschwind
Journal: Genome Medicine (2014)

Common genetic variation and rare mutations in genes encoding calcium channel subunits have pleiotropic effects on risk for multiple neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. To gain further mechanistic insights by extending previous gene expression data, we constructed co-expression networks in Timothy syndrome (TS), a monogenic condition with high penetrance for ASD, caused by mutations in the L-type calcium channel, Cav1.2.To identify patient-specific alterations in transcriptome organization, we conducted a genome-wide weighted co-expression network analysis (WGCNA) on neural progenitors and neurons from multiple lines of induced pluripotent stem cells (iPSC) derived from normal and TS (G406R in CACNA1C) individuals. We employed transcription factor binding site enrichment analysis to assess whether TS associated co-expression changes reflect calcium-dependent co-regulation.We identified reproducible developmental and activity-dependent gene co-expression modules conserved in patient and control cell lines. By comparing cell lines from case and control subjects, we also identified co-expression modules reflecting distinct aspects of TS, including intellectual disability and ASD-related phenotypes. Moreover, by integrating co-expression with transcription factor binding analysis, we showed the TS-associated transcriptional changes were predicted to be co-regulated by calcium-dependent transcriptional regulators, including NFAT, MEF2, CREB, and FOXO, thus providing a mechanism by which altered Ca(2+) signaling in TS patients leads to the observed molecular dysregulation.We applied WGCNA to construct co-expression networks related to neural development and depolarization in iPSC-derived neural cells from TS and control individuals for the first time. These analyses illustrate how a systems biology approach based on gene networks can yield insights into the molecular mechanisms of neural development and function, and provide clues as to the functional impact of the downstream effects of Ca(2+) signaling dysregulation on transcription.
Bed-Population Ratios
Authors: Donald A. Hammel
Journal: JAMA (1978)

To the Editor.—  The article  Services in the Netherlands (239: 1558, 1978) quotes hospital usage figures of 1.688 inpatient days per 1,000 population and an average length of stay of 16.6 days.  Calculation, using an average occupancy of 90%, results in a bed-population ratio of 5.14 beds per 1,000. (At 85%, a figure often quoted by health care planners as desirable, the figure is 5.44.)  Since this is the requirement for a modern, industrialized, progressive, fairly homogenous population, determined by experience and where a well-established system of government monitoring directs its attention particularly toward quality of services, sufficient and efficient facilities, and use of these facilities for both inpatient and outpatient services (much as our developing Professional Standards Review Organizations and Health Systems Agencies are attempting to do), why, then, are the bed-population guidelines issued by the Department of Health, Education, and Welfare (DHEW) more than 20% lower? It
New Reports Examine Psychiatric Risks of Varenicline for Smoking Cessation
Authors: Bridget M. Kuehn
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Smoking and Cervical Cancer: Cause or Coincidence?
Authors: Peter M. Layde
Journal: JAMA (1989)

In the debate on the role of cigarette smoking in the etiology of cervical cancer, there is one central point of agreement: women who smoke cigarettes are more likely to develop cervical neoplasia than are nonsmokers. Beyond that key point, however, there is considerable controversy. The basic question is whether the association of smoking and cervical cancer is causal, mediated by some biologically plausible mechanism, or artifactual, produced by some extraneous confounding difference between smokers and nonsmokers. The noteworthy article by Slattery and collegues<sup>1</sup>in this issue ofThe Journalwill open a new controversy in this area by suggesting an etiologic role of passive exposure to the smoke of others' cigarettes in cervical carcinogenesis. In addition, Slattery and colleagues have reopened the long-standing, more general debate about whether cervical cancer should be added to the list of tobacco-induced cancers. Winkelstein's<sup>2</sup>insightful recognition of the similarity of cervical
STUDIES ON INFLAMMATION
Authors: Valy Menkin
Journal: The Journal of Experimental Medicine (1931)

India ink or graphite partides injected into an area of inflammation fail to disseminate to the tributary lymph nodes. When injected into a normal peritoneal cavity they rapidly appear in the retrosternal lymph nodes. When injected into an inflamed peritoneal cavity they are fixed in situ and fail to reach the regional lymph nodes. Graphite particles injected in the circulating blood stream enter an inflamed area both as free particles owing to increased capillary permeability and also as phagocyted material within leucocytes. Bacteria (B. prodigiosus) injected into inflamed tissue are fixed at the site of inflammation and fail to disseminate to the regional lymph nodes as readily as when injected into normal tissue. Bacteria (B. prodigiosus) injected at the periphery of an inflamed area do not readily penetrate into the site of inflammation. The experiments furnish evidence, in addition to that already provided, that fixation of foreign substances by the inflammatory reaction is primarily due to mechanical obstruction caused by a fibrin network and by thrombosed lymphatics at the site of inflammation. Bacteria (B. prodigiosus and B. pyocyaneus) injected intravenously rapidly enter an inflamed area. It is suggested that localization of bacteria in a locus minoris resistentiae may be explained as the result of increased capillary permeability with subsequent accumulation and fixation of bacteria from the blood stream at the point of injury.
Antoni van Leeuwenhoek
Authors: A. Schierbeek
Journal: JAMA (1962)

<h3>To the Editor:—</h3> In the editorial on Leeuwenhoek, entitled "The Bedellus of Delft" (<i>JAMA</i><b>177</b>:860-861 [Sept. 23] 1961), several items appeared to me to be incorrect. As a former editor-in-chief of "The Collected Papers of A. v. Leeuwenhoek," I should like to comment on the following: The statement is made that "Leeuwenhoek was not the first to discover microscopical organisms." I believe that he was unquestionably the discoverer of his "little animals." In addition to being janitor or bedellus, he was also a wine-gauger of Delft ( 1679 ) and passed an examination for surveyor (1669). Instead of 375 letters written to the Royal Society, the number is approximately 250. The definition of a "book" should be liberal. Sheafs of his "letters" were prepared in Latin as well as Dutch and are available in several editions. These should be considered as books. There are several microscopes extant. I have proved in
INDUCTION OF A HEMOLYSIN RESPONSE IN VITRO
Authors: Klaus-Ulrich Hartmann
Journal: The Journal of Experimental Medicine (1970)

The immune response to foreign erythrocytes was studied in vitro. Two subpopulations of cells were prepared. One was a population of bone marrow-derived spleen cells, taken from thymectomized, irradiated, and bone marrow-reconstituted mice; there was evidence that most of the precursors of the PFC had been present in this cell population, but few PFC developed in cultures of these cells alone in the presence of immunogenic erythrocytes. Another cell suspension was made from spleens of mice which had been irradiated and injected with thymus cells and erythrocytes; these cells were called educated T cells. The two cell suspensions together allow the formation of PFC in the presence of the erythrocytes which were used to educate the T cells, but not in the presence of noncross-reacting erythrocytes. If bone marrow-derived cells and T cells were kept in culture together with two different species of erythrocytes, and if one of the erythrocytes had been used to educate the T cells, then PFC against each of the erythrocytes could be detected.
Cranial Irradiation in Cancer of the Lung of All Cell Types
Authors: James D. Cox, Kenneth Stanley, Zbigniew Petrovich, Camilo Paig, Raymond Yesner
Journal: JAMA (1981)

The Veterans Administration Lung Group conducted a prospective study of irradiation for subclinical brain metastases in patients with inoperable carcinoma of the lung between 1975 and 1978. Patients were randomized to receive whole-brain irradiation (2,000 rads in two weeks) or no brain treatment, and to receive one of two regimens of thoracic irradiation. Three hundred twenty-three patients with normal radionuclide brain scans were able to be evaluated. The rate of clinical brain metastasis was 26% for patients with small cell carcinoma vs 10% for the "non-small-cell" group. A statistically insignificant decrease in the rate of brain metastasis was found among irradiated patients with small cell carcinoma. The frequency of brain metastasis in the non-small-cell patients was reduced from 13% to 6% by irradiation. Prophylactic cranial irradiation can decrease morbidity from non-small-cell carcinoma of the lung.
PIK3CA Mutations Are Not a Major Determinant of Resistance to the Epidermal Growth Factor Receptor Inhibitor Cetuximab in Metastatic Colorectal Cancer
Authors: Hans Prenen, Jef De Schutter, Bart Jacobs, Wendy De Roock, Bart Biesmans, Bart Claes, Diether Lambrechts, Eric Van Cutsem, Sabine Tejpar
Journal: Clinical Cancer Research (2009)

It has been reported that activating KRAS mutations negatively affect response to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. The mutation status of signaling molecules downstream of the EGFR target is thus crucial to predict clinical benefit to EGFR-targeted therapies. Other mechanisms of resistance to EGFR inhibitors could involve activating mutations of the other main EGFR effector pathway, i.e., the PI3K/PTEN/AKT pathway.We analyzed the PIK3CA and KRAS mutation status in a large group (n = 200) of chemorefractory metastatic colorectal cancers treated with cetuximab (Erbitux) in monotherapy or in combination with irinotecan, and correlated the mutation status with outcome.Twenty-three (12%) of the 200 samples carried 1 of the PIK3CA mutations included in our assay. We found no correlation between the presence of a PIK3CA mutation and impaired response to cetuximab.Our findings do not provide any evidence for a strong role of PIK3CA mutations as a single marker in determining response to cetuximab in chemorefractory metastatic colorectal cancer.
Lactulose in the Treatment of Chronic Portal-Systemic Encephalopathy
Authors: S. G. Elkington, M. H. Floch, H. O. Conn
Journal: New England Journal of Medicine (1969)

Abstract Current methods of controlling chronic portal-systemic encephalopathy (PSE) are unsatisfactory. Recently, lactulose treatment has been proposed. This synthetic disaccharide, which is neither absorbed nor hydrolyzed in the small bowel, is degraded by colonic bacteria, decreasing the pH of the colonic contents. In five of seven cirrhotic patients with PSE studied in a double-blind trial using sorbitol as control treatment, lactulose caused improvement that was associated with decreased stool pH and arterial ammonia levels and improvement in EEG. Sorbitol had no such effects. In seven patients long-term administration of lactulose was effective in preventing or ameliorating episodes of PSE despite discontinuing neomycin and doubling the daily protein intake. No consistent qualitative or quantitative alteration in stool flora was demonstrated. Improvement correlated with effective fecal acidification. Lactulose appears to exert its action by diminishing the absorption of ammonia from the acidified co...
National audit shows improvements in hospital care of hip fracture patients
Authors: I. Torjesen
Journal: BMJ (2011)

The care of elderly patients with hip fracture has improved over the past year as a government initiative giving financial incentives to trusts that meet quality standards begins to yield results, an audit has shown.

The national hip fracture database report, published this week, includes data on more than 53 000 cases of people admitted to hospitals in England, Wales, Northern Ireland, and the Channel Islands between April 2010 and March 2011—around 76% of the 70 000 estimated cases.

The audit, a collaboration of the British Geriatric Society and British Orthopaedic Association with funding from the Healthcare Quality Improvement Partnership, found that over the past year the quality of care of patients with hip fracture has continued to improve, in some areas markedly.

And in 2010-11 the Department of Health for England also introduced an added incentive to hospital trusts to improve …
Role of hepatic STAT3 in brain-insulin action on hepatic glucose production
Authors: Hiroshi Inoue, Wataru Ogawa, Akihiro Asakawa, Yasuo Okamoto, Akihiko Nishizawa, Michihiro Matsumoto, Kiyoshi Teshigawara, Yasushi Matsuki, Eijiro Watanabe, Ryuji Hiramatsu, Kenji Notohara, Koji Katayose, Hitoshi Okamura, C. Ronald Kahn, Tetsuo Noda, Kiyoshi Takeda, Shizuo Akira, Akio Inui, Masato Kasuga
Journal: Cell Metabolism (2006)
US doctor warns of misuse of prescribed stimulants
Authors: C. Marwick
Journal: BMJ (2003)

Europe is being targeted by the drugs industry as the next major market for increasing the use of stimulant drugs such as methylphenidate (Ritalin) and dexamfetamine, a Californian doctor specialising in behavioural paediatrics warned at a recent meeting of the President's Bioethics Council.

Dr Lawrence Diller has become known in the United States as a critic of the inappropriate use of stimulants such as methylphenidate for the management of children with attention deficit hyperactivity disorder. Besides its therapeutic uses methylphenidate has also attracted non-therapeutic uses: pacifying unruly children, enhancing performance, and, as Dr Diller …
Hypercalcemia in Disseminated Coccidioidomycosis
Authors: Joseph C. Lee, Antonino Catanzaro, Jacqueline G. Parthemore, Brian Roach, Leonard J. Deftos
Journal: New England Journal of Medicine (1977)

Infectious diseases are seldom considered in the differential diagnosis of hypercalcemia.1 , 2 Bacterial, and perhaps viral, infections have only rarely been associated with an elevated blood calcium, and this complication does not seem to occur in fungal diseases.3 , 4 In the three patients described below disseminated coccidioidomycosis was associated with hypercalcemia.. Case ReportsCase 1. A 31-year-old man was hospitalized September, 1974, with a two-week history of cough and fever (temperature of 38.9°C). Cultures of the bone marrow, skin lesions and sputum grew Coccidioides immitis. A roentgenogram showed a cavity in the right lower lobe consistent with this diagnosis. Cerebrospinal-fluid . . .
Intraoperative rendezvous endoscopic retrograde cholangiopancreatography for choledocholithiasis: what about big stones?
Authors: F. Froehlich
Journal: Endoscopy (2007)

I read with great interest the recent article by Ràbago et al. [1]. The authors are to be congratulated on this prospective randomized study of patients with choledocholithiasis in which they compared preoperative endoscopic retrograde cholangiopancreatography (ERCP) followed by cholecystectomy with intraoperative ERCP (using the rendezvous technique) during cholecystectomy. The results were convincingly in favor of intraoperative ERCP, with less morbidity, a shorter hospital stay, and reduced costs.
Combination of trichosanthes cucumerina L. compounds: an analysis for novel effects of anticancer cell activites as probes for pharmacological studies
Authors: Md Ariful Haque Mollik
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Prostate cancer is a hormone-dependent cancer and its proliferation is stimulated by endogenous steroid hormones. Aromatase (CYP19) and 5α-reductase (SRD5A) are the key enzymes that synthesize these hormones. Aromatase converts androgens to estrogens and 5α-reductase converts
Streptomycin
Authors: Roderick Murray, Tom F. Paine, Maxwell Finland
Journal: New England Journal of Medicine (1947)

SEVERAL months have elapsed since streptomycin became available in this country for use in hospitals and then to physicians generally. Heralded at first as the final fruit of victory in the battle against bacterial infections, it seemed to be the obvious and natural supplement to penicillin and was to fill the few gaps among the infections that could not be disposed of by that potent agent. Experiences with penicillin, however, had conditioned the practitioner to expect from streptomycin brilliant, rapid and consistent results in susceptible infections and with essentially no untoward effects.It soon became apparent, however, that none of . . .
Tercentenary of the Death of William Harvey 1. The Growth of Truth
Authors: W. Osler
Journal: BMJ (1957)

Personality of William Harvey," says this of the portrait " It was acquired very early in the eighteenth century by the famous Dr. Mead, who knew all the famous men of his time, including some that must have known Harvey.At the sale of Mead's collection in 1754 it was bought for Hunter, and in his collection it has remained ever since.It is a much less formal, more intimate, picture of Harvey than the ceremonial portrait at the College of Physicians.He does not look a very happy or satisfied man, as we have reason to know that he was not.The characteristic eyebrow is there, and the complexion in the picture itself entirely agrees with Aubrey's description as olivaster, the colour of wainscot.The patches on the cheeks are due to high colour, agreeing with Aubrey's description of his hot-headedness, and our knowledge that his blood-pressure was certainly raised in his last years.Notice also the faithful rendering of the distended temporal vein.But you may ask, why does he finger the leaves of a book with a Vesalian engraving of a skull, and why a background representing a view of Rome ?The book is the Works of Spigelius, i645.It happens to contain a reprint of Harvey's De Motu Cordis, but in fact it serves also to remind us that Harvey was a general anatomist, not merely the demonstrator of the circulation of the blood.The background shows the Church of S. Maria de Loreto and Trajan's Column ; for Harvey had visited Rome in l 636, and the library he had built for the College of Physicians was inspired by an admiration for Roman architecture. . . .The Hunterian portrait is, then, almost, 9f not quite, the most interesting representation of Harvey in his old age that we possess, and there are a number of other portraits derived from it, including the well-known engraving by Houbraken."
Alarmin interleukin 33 is overexpressed in psoriasis and induces ST2-dependent psoriasis-like dermatitis
Authors: A. J. Hueber, A. M. Miller, D. L. Asquith, N. L. Millar, D. Gilchrist, A. Gracie, I. B. McInnes
Journal: Annals of the Rheumatic Diseases (2010)

In summary, the authors demonstrate that IL33 can induce skin infl ammation and may be a key player in the initiation of psoriasis plaque formation; furthermore, this might explain a role for IL33 in 'deep Koebner's phenomenon' for initiation of psoriatic arthritis.
Attenuation Artifact From Sclerotic Bone Can Mimic Active Bone Metastasis on PET-CT
Authors: Linh Ho, John Seto
Journal: Clinical Nuclear Medicine (2006)

We report the PET-CT appearance of sclerotic bone mimicking active bone metastasis in a 57-year-old woman with right breast cancer and bone and hepatic metastases. Hybrid PET-CT was performed 1 month after completion of surgery and chemoradiation treatment. PET-CT demonstrated hypermetabolic foci in the right pulmonary hilum and liver. Increased hypermetabolic activity in L1 and L3 vertebral bodies was also seen corresponding to sclerotic vertebral bodies on CT study. The activity in L1 and L3 vertebral bodies was not visualized on nonattenuation-corrected images, consistent with an attenuation correction artifact resulting from extensive sclerosis in these regions.
Potential Role of Tamoxifen in Prevention of Breast Cancer
Authors: S. G. Nayfield, J. E. Karp, L. G. Ford, F. A. Dorr, B. S. Kramer
Journal: JNCI Journal of the National Cancer Institute (1991)

Despite advances in early detection and treatment of breast cancer, primary prevention has not been well explored, especially for women at increased risk of disease due to reproductive factors and family history. There are, however, suggestions that primary prevention of breast cancer may be a realistic objective. Randomized clinical trials of adjuvant therapy for early-stage breast cancer have demonstrated a 35% decrease in contralateral breast cancers among women receiving tamoxifen compared with controls, suggesting a potential role for tamoxifen in chemoprevention of breast cancer in women at increased risk of the disease. Adjuvant therapy studies also demonstrate that tamoxifen is well tolerated by most patients and suggest additional health benefits from alterations in plasma lipid levels and stabilization of bone mineral loss in women receiving tamoxifen. Aspects of tamoxifen pharmacology, laboratory research, and clinical experience which support its investigation as a chemopreventive agent for breast cancer are summarized, and potential toxic effects are discussed. [J Natl Cancer Inst 83: 1450–1459, 1991]