tbuckley/cabot-search huggingface dataset:
A2.23 Impaired Natural Killer Cell Function in DOCK8 Deficiency
Authors: MC Mizesko, PP Banerjee, L Monaco-Shawver, EM Mace, W Bernal, J Sawalle-Belohradsky, B Belohradsky, V Heinz, AF Freeman, KE Sullivan, SM Holland, TR Torgerson, W Al-Herz, J Chou, IC Hanson, MH Albert, RS Geha, ED Renner, JS Orange
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Introduction</h3> DOCK8 mutations are responsible for a rare autosomal recessive immunodeficiency syndrome associated with severe cutaneous viral infections, elevated IgE levels, environmental allergies, autoimmunity, and malignancy. DOCK8 activates CDC42, which is important for cell signalling and actin reorganisation. Natural killer cells play a vital role in tumour surveillance and defence against virally infected cells. NK cell function relies on the accumulation of actin at the NK cell immunologic synapse formed with target cells. Although abnormalities in T and B cell function have been described in DOCK8-deficient patients, the role of NK cells in this disease is poorly understood. <h3>Objectives/Aims</h3> Given the susceptibility to severe cutaneous viral infection and malignancy, we hypothesised there was a substantive defect in NK cell function in patients with DOCK8 deficiency. <h3>Methods</h3> 10 patients with genetically confirmed DOCK8 deficiency as well as NK cell lines with stably reduced DOCK8 expression were evaluated experimentally using in vitro NK cell cytotoxicity, F-actin content, and confocal immunofluorescence microscopy assays. <h3>Results</h3> DOCK8-deficient patients and cell lines all had decreased NK cell cytotoxicity and function could not be restored after IL-2 stimulation. Importantly, DOCK8 deficiency did not affect NK cell F-actin content, but impaired F-actin accumulation at the lytic immunological synapse. <h3>Conclusions</h3> DOCK8 deficiency results in severely deficient NK cell function owing to an inability to form a mature lytic immunological synapse via focal F-actin accumulation. This defect may underlie important and previously perplexing attributes of the DOCK8 deficiency clinical syndrome including the unusual susceptibility to viral infection.
Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide<i>Vibrio cholerae</i>spatial cues within the small intestine
Authors: Benjamin J Koestler, Christopher M Waters
Journal: Gut Microbes (2014)

The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in response to environmental stimuli to enable bacteria to transition between different lifestyles. Here we discuss our recent findings that the human pathogen Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to regulate intracellular c-di-GMP. We have demonstrated that bile acids increase intracellular c-di-GMP to promote biofilm formation. We have also shown that this bile-mediated increase of intracellular c-di-GMP is negated by bicarbonate, and that this interaction is dependent on pH, suggesting that V. cholerae uses these 2 environmental cues to sense and adapt to its relative location in the small intestine. Increased intracellular c-di-GMP by bile is attributed to increased c-di-GMP synthesis by 3 diguanylate cyclases (DGCs) and decreased expression of one phosphodiesterase (PDE) in the presence of bile. The molecular mechanisms by which bile controls the activity of the 3 DGCs and the regulators of bile-mediated transcriptional repression of the PDE are not yet known. Moreover, the impact of varying concentrations of bile and bicarbonate at different locations within the small intestine and the response of V. cholerae to these cues remains unclear. The native microbiome and pharmaceuticals, such as omeprazole, can impact bile and pH within the small intestine, suggesting these are potential unappreciated factors that may alter V. cholerae pathogenesis.
Signs of love, not a love potion
Authors: J. Aronson
Journal: BMJ (2003)

Gunther Weitz has described the symptoms experienced by Tristan and Isolde in Wagner's opera after they have drunk the love potion. He concludes that the potion is likely to have contained an anticholinergic compound or compounds. This is an amusing idea, but to treat it seriously trivialises Wagner's opera.

The legend of Tristan (or Tristram) and Iseult (or Isolde) is from the 6th century but was not written down until the 12th century, when it became exceptionally popular, spawning about 80 versions in the next 100 or so years. Its popularity has not waned in 850 years. The first still extant version (circa 1150) was by the French poet Thomas, and later French versions are by Beroul (c 1180), Marie de France (c 1190), and Helie de Borron (c 1190). Gottfried von Strassburg's early 13th century unfinished version (c 1210) relied on that of Thomas; in completing it, Ulrich von Turheim and Heinrich von Freiburg relied on a late 12th century version by Eilhart of Oberg.

In most versions the love potion is made by Iseult's mother when her daughter is about to be escorted by Tristan to Cornwall to marry King Mark, with the instruction to Iseult's nurse, Brangien (Brangane) that it is to be given to Iseult and Mark on their wedding …
5-Fluorouracil in the Treatment of Gastrointestinal Neoplasia
Authors: Sheldon Kaufman
Journal: New England Journal of Medicine (1973)

FLUOROURACIL has been available for clinical use since 1958, and has been reported to produce objective tumor regressions in 11 to 50 per cent of patients with far advanced gastrointestinal cancer. For the most part, patients are treated by the method first advocated by Curreri1 and Ansfield2 and their co-workers, in which a loading course of 15 mg per kilogram of body weight is given by intravenous injection daily for four or five days, followed by maintenance doses of 7.5 mg per kilogram every other day until toxicity occurs. This regimen produces toxicity in most patients and a reported mortality . . .
the C-Rel Subunit of Nuclear Factor-κB Regulates Murine Liver Inflammation, Wound-Healing, and Hepatocyte Proliferation
Authors: Roben G. Gieling, Ahmed M. Elsharkawy, Jorge H. Caamaño, David E. Cowie, Matthew C. Wright, Mohammad R. Ebrahimkhani, Alastair D. Burt, Jelena Mann, Pradip Raychaudhuri, Hsiou-Chi Liou, Fiona Oakley, Derek A. Mann
Journal: Hepatology (2009)

In this study, we determined the role of the nuclear factor-kappaB (NF-κB) subunit c-Rel in liver injury and regeneration. In response to toxic injury of the liver, c-Rel null ( c-rel −/−) mice displayed a defect in the neutrophilic inflammatory response, associated with impaired induction of RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted; also known as CCL5). The subsequent fibrogenic/wound-healing response to both chronic carbon tetrachloride and bile duct ligation induced injury was also impaired and this was associated with deficiencies in the expression of fibrogenic genes, collagen I and α-smooth muscle actin, by hepatic stellate cells. We additionally report that c-Rel is required for the normal proliferative regeneration of hepatocytes in response to toxic injury and partial hepatectomy. Absence of c-Rel was associated with blunted and delayed induction of forkhead box M1 (FoxM1) and its downstream targets cyclin B1 and Cdc25C. Furthermore, isolated c-rel −/− hepatocytes expressed reduced levels of FoxM1 and a reduced rate of basal and epidermal growth factor–induced DNA synthesis. Chromatin immunoprecipitation revealed that c-Rel binding to the FoxM1 promoter is induced in the regenerating liver. Conclusion: c-Rel has multiple functions in the control of liver homeostasis and regeneration and is a transcriptional regulator of FoxM1 and compensatory hepatocyte proliferation. (Hepatology 2010.)
COMPLETE CORONARY REVASCULARIZATION IN DIFFERENT CLINICAL SETTINGS IS NOT ENOUGH: ROLE OF RANOLAZINE
Authors: Simone Calcagno, Temistocle Taccheri, Roberta Carnesale, Salvi Nicol, Maria Lembo, Pasqualina Bruno, Alberto Fo, Aurora I. Danza, Massimo Mancone, Francesco Fedele
Journal: Journal of the American College of Cardiology (2014)
Emergency Care in Small Hospitals
Authors: Charles C. Voorhis
Journal: JAMA (1965)

<h3>To the Editor:—</h3> The wail of the siren, the crunch of tires on the driveway, and the intermittent red flash on the opaque windows of the accident room are sights and sounds familiar to the emergency service. They are more familiar to those of us who work in the smaller hospitals. Here there is no highly trained resident staff to give treatment under the supervision of the staff surgeon. Instead we do the work ourselves with the assistance of nurses and one or two second year residents. I am not minimizing their help, but observing the greater burden on the attending physician under these circumstances. What would happen to our families if we were involved in an auto accident while traveling? To be sure, near home the best of care would be afforded. But what about the care received in the smaller hospitals of 75 to 150 beds in rural
Neuronal Elav-like (Hu) Proteins Regulate RNA Splicing and Abundance to Control Glutamate Levels and Neuronal Excitability
Authors: Gulayse Ince-Dunn, Hirotaka J. Okano, Kirk B. Jensen, Woong-Yang Park, Ru Zhong, Jernej Ule, Aldo Mele, John J. Fak, ChingWen Yang, Chaolin Zhang, Jong Yoo, Margaret Herre, Hideyuki Okano, Jeffrey L. Noebels, Robert B. Darnell
Journal: Neuron (2012)
Variants of intestinal metaplasia in the evolution of chronic atrophic gastritis and gastric ulcer. A follow up study.
Authors: S Silva, M I Filipe, A Pinho
Journal: Gut (1990)

A follow up study with biopsy was initiated in 1982 to define the relations between variants of intestinal metaplasia and the evolution of chronic atrophic gastritis and gastric ulcer. All patients (58 with chronic atrophic gastritis and 66 with gastric ulcer) had intestinal metaplasia at the start of the study. In the six year period to 1988 a total of 241 biopsies were performed on the patients with chronic atrophic gastritis and 243 on the patients with gastric ulcer. Initially, 81% of the patients with chronic atrophic gastritis presented with type I intestinal metaplasia and 14% with type III intestinal metaplasia. During follow up type I was predominant, often associated with grades 2 and 3 active disease (81%) and 45% of these patients reverted to a non-intestinal metaplasia status by the third year of follow up. In contrast, type III metaplasia was more common in the absence of appreciable inflammation (78% of biopsy specimens), being persistent in five of seven patients in the third year of follow up, and was found to be associated with dysplasia in three of these patients. Similarly, the initial biopsy specimen showed type I metaplasia in most patients with gastric ulcer (82%) and type III in only 4%. Type I metaplasia was also predominant in these patients (80%), particularly in active disease (68%), gradually regressing with healing. In contrast, type III was associated with delayed ulcer healing and reactivation (75%; six of eight patients). We conclude that (a) type I is a short term reactive process which regresses with healing; (b) type III is related to prolonged injury and chronicity and may regress or progress to dysplasia; (c) persistent and more immature forms of metaplasia may carry an increased risk of malignancy.
Hyperthyroidism in Identical Twins
Authors: Jerold M. Lowenstein
Journal: JAMA (1961)

HYPERTHYROIDISM in identical twins is extremely rare. Reviewing the world literature in 1941, Bartels<sup>1</sup>found 10 authenticated sets. Boas, in an article on hereditary exophthalmic goiter,<sup>2</sup>cites 4 reported pairs of twins, only 1 pair being males. This is another report of exophthalmic goiter in male identical twins. One brother developed the disease at 19 years of age, and the other followed within a year. Both had severe neutropenia while in the hyperthyroid state, prior to antithyroid drug therapy, and both neutrophil counts increased after definitive treatment of the thyroid disease. The first was cured by subtotal thyroidectomy. His brother proved more difficult to prepare for surgery—his neutrophil level dropped on antithyroid therapy—and he eventually was treated with radioactive iodine. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 19-year-old Negro man had been well until December, 1954, when he began having nervousness, insomnia, profuse perspiration, tremor, loose stools, and
O6 alkylguanine-DNA alkyltransferase activity in human myeloid cells.
Authors: S L Gerson, K Miller, N A Berger
Journal: Journal of Clinical Investigation (1985)

The association between alkylating agent exposure and acute nonlymphocytic leukemia in humans indicates that myeloid cells may be particularly susceptible to mutagenic damage. Alkylating agent mutagenesis is frequently mediated through formation and persistence of a particular DNA base adduct, O6alkylguanine, which preferentially mispairs with thymine rather than cytosine, leading to point mutations. O6alkylguanine is repaired by O6alkylguanine-DNA alkyltransferase (alkyltransferase), a protein that removes the adduct, leaving an intact guanine base in DNA. We measured alkyltransferase activity in myeloid precursors and compared it with levels in other cells and tissues. In peripheral blood granulocytes, monocytes, T lymphocytes, and B lymphocytes, there was an eightfold range of activity between individuals but only a twofold range in the mean activity between cell types. Normal donors maintained stable levels of alkyltransferase activity over time. In bone marrow T lymphocytes and myeloid precursors, there was an eightfold range of alkyltransferase activity between donors. Alkyltransferase activity in the two cell types was closely correlated in individual donors, r = 0.69, P less than 0.005, but was significantly higher in the T lymphocytes than the myeloid precursors, P less than 0.05. Liver contained the highest levels of alkyltransferase of all tissues tested. By comparison, small intestine contained 34%, colon 14%, T lymphocytes 11%, brain 11%, and myeloid precursors 6.6% of the activity found in liver. Thus, human myeloid precursors have low levels of O6alkylguanine-DNA alkyltransferase compared with other tissues. Low levels of this DNA repair protein may increase the susceptibility of myeloid precursors to malignant transformation after exposure to certain alkylating agents.
Use of terbinafine in HIV-positive subjects: pilot studies in onychomycosis and oral candidiasis
Authors: R. NANDWANI, A. PARNELL, M. YOULE, C.J.N. LACEY, E.G.V. EVANS, J. MIDGLEY, J. CARTLEDGE, D.A. HAWKINS
Journal: British Journal of Dermatology (1996)

Study 1. Eighteen HIV-positive Caucasian homosexual men with initial positive fungal microscopy were recruited into this prospective, dual-centre, open-label study. They received a once-daily oral dose of 250 mg terbinafine for 12 weeks. Eight were subsequently excluded after screening cultures proved negative. The mean CD4 count of the 10 evaluable subjects was 302/mm3. All 10 positive fungal cultures were confirmed as Trichophyton rubrum. Using an intention-to-treat analysis, healthy unaffected nail growth increased from a mean of 1.6 mm at baseline to 5.2 mm after 12 weeks' treatment. Clinical response after treatment was 6.4 mm at 36 weeks and 8.0 mm at 48 weeks. Three of the 10 toenail infections were cured mycologically. This 30% cure rate was maintained over 48 weeks' follow-up, despite three patients discontinuing the study. One withdrew following a terbinafine-induced drug rash. Two others stopped treatment during HIV-related illnesses, but without terbinafine side-effects. Study 2. Ten HIV-positive subjects, nine culture-positive for Candida albicans and one for Candida albicans and Candida glabrata, were recruited into this pilot study. They received 250 mg oral terbinafine daily for 14 days. Their average CD4 count was 131/mm3. All patients remained culture-positive throughout the study. Slight improvements in signs and symptoms were seen in one or two patients but this might well have been attributable to improved oral hygiene. Oral terbinafine at this dosage was therefore not thought an effective treatment for this indication in HIV-positive patients. The drug was well tolerated and no serious treatment-related adverse events were reported.
IDH1 and IDH2 mutations are rare in pediatric myeloid malignancies
Authors: K Oki, J Takita, M Hiwatari, R Nishimura, M Sanada, J Okubo, M Adachi, M Sotomatsu, A Kikuchi, T Igarashi, Y Hayashi, S Ogawa
Journal: Leukemia (2011)
A Clinical Lecture on some Anomalous Cases of Tabes Dorsalis: Delivered at the National Hospital for the Paralysed and Epileptic, Queen Square, on July 8th, 1902
Authors: J. Taylor
Journal: BMJ (1902)

THE subject which I have chosen for my lecture to-day is, as you are aware that of anomalous cases of tabes dorsalis.have chosen tLis subject because I have been very strack recently with the curiously variable character of this disease, and with the cases which have come before me oftea almost unrecognizable in their symptomatology and in their course and in their susceptibility to treatment.It is difficult to know what one ought to reckon as anomalous cases of tabes, because we have not any definite type which to start as the normal condition of disease, if so call it.But looking upon tabes dorsalis as a essentially of the afferent system characterized by wasting the spinal cord, in the posterior region especially, and as its chief symptoms difficulty or ataxy in walking using the upperLimbs, lightning pains, girdle sensation, and interference with the action of the sphincters, I should as anomalous, at least for the'purposes of this lecture, cases clearly recognized by certain signs as belonging to category, but differing in any important respect.I should inclined to divide such cases into two classes: First, which symptoms referable to the eye are the chief manifestation of disease; and, secondly, those characterized obtrusiveness of various unusual conditions such crises, joint troubles, perforating ulcer, or other changes.But 1 must not be understood to in this latter group may not also have the phenomena of the ordinary disease, or may not -optic atrophy or ocular paralyses superadded to the have mentioned.With reference to the first group of cases, those, namely, in which ocular symptoms or symptoms attributable disease of the optic nerve are the chief ones, I should that many of them are seen in their earlier stage thalmic surgeons, who are naturally consulted
Big Pharma would like to befriend you
Authors: J. Lenzer
Journal: BMJ (2011)

Online social media such as Facebook, Twitter, and YouTube are a “gold mine” where the “sky is the limit” for drug companies, a marketing expert has said.

During a recent “webinar” on how drug companies can expand their presence in social media, Adam Kleger, vice president of business development at ListenLogic Health, a social intelligence company serving the pharmaceutical and healthcare industries, told the audience that the industry can use social media to create “personal relationships” with patients and healthcare providers—relationships he likened to “going to a cocktail party or a wedding reception” where information is exchanged.

The benefits of “social CRM” (customer relationship management), said Mr Kleger, include the ability to direct patients to branded drug sites, recruit patients into clinical trials, and to collect business intelligence on patients and healthcare providers. It also allows the industry to identify “KOOLs” (key online opinion leaders).

The webinar was sponsored by PharmaLive, a project of UBM Canon, which is based in Newton, Pennsylvania, and which provides the “$500bn pharmaceutical industry with need-to-know business information.”

Mr Kleger said that obtaining intelligence on doctors and other healthcare providers can be difficult, as most avoid conversations on public websites. However, some “innovative companies” have managed to monitor private sites, such as those …
DERMATITIS VENENATA DUE TO CHRYSANTHEMUM LEAVES
Authors: Marvin B. Goldstein
Journal: JAMA (1931)

In looking through the literature, I have been unable to find mention of any cases of dermatitis venenata due to chrysanthemum leaves. I am reporting a case recently treated: <h3>REPORT OF CASE</h3> F. B., aged 63, a greenhouse employee, seen, Oct. 21, 1930, had had a severe, itching skin eruption present for the past ten months. It happened to be getting worse. He never had skin trouble before the present attack. He had been employed in his present position for seven years. He was married and his past medical and family histories were irrelevant. The patient was of small stature. He was poorly nourished and evidently had lost some weight. He had a large right inguinal hernia; but nothing else abnormal, outside of the dermatologic condition, was discovered. The skin eruption was generalized but was most marked over the face, neck, arms and buttocks. The eruption consisted of diffuse erythematous,
A histological semiquantitative scoring system for evaluation of hepatic fibrosis in needle liver biopsy specimens: Comparison with morphometric studies
Authors: Michéle Chevallier, Sylviane Guerret, Philippe Chossegros, Françoise Gerard, Jean-Alexis Grimaud
Journal: Hepatology (1994)

The evaluation of hepatic fibrosis on histological sections is of great interest for the staging and follow-up of chronic liver disease. Because no reliable scoring system is yet available, we have designed a semiquantitative scoring system in which the four main sites of fibrotic deposit — centrilobular vein, portal tract and perisinusoidal space, together with width and number of septa when present — are analyzed. These different items have been previously settled from comparison with morphometric measurements to evaluate surface density of total collagen performed on the same liver needle biopsy specimens stained with picro-sirius. The score has been tested on samples from 200 consecutive patients with various liver diseases and compared with the surface density of total collagen and Knodell scoring system. For observer variation study, the features by three independent pathologists were coded on 20 cases. There was a good interobserver (Kendall's τ-B=0.75) and intraobserver (τ-B=0.73) reproducibility. Each component of the fibrosis scoring system and total collagen surface density were significantly linearly related (one-way polynomial analysis, p<10−4); the correlation between semiquantitative scoring system and surface density of total collagen was 0.73 (p<10−5). Our semiquantitative scoring system, simple and reproducible, describes both liver architecture and fibrotic deposit. It is better related to morphometric measurement of fibrosis than each of its constituents or than the fibrosis item of the Knodell scoring system. It represents a reliable and convenient method for fibrosis evaluation, which is mandatory for clinical use. (Hepatology 1994;20:349–355.)
THE TREATMENT OF ESSENTIAL HYPERIDROSIS WITH HEXAMETHONIUM BROMIDE: A PRELLAIINARY REPORT
Authors: JAMES SOMMERVILLE, J. B. MACMILLAN
Journal: British Journal of Dermatology (1952)

Journal Article THE TREATMENT OF ESSENTIAL HYPERIDROSIS WITH HEXAMETHONIUM BROMIDE: A PRELLAIINARY REPORT Get access JAMES SOMMERVILLE, M.B., F.R.F.P.S.(G.), JAMES SOMMERVILLE, M.B., F.R.F.P.S.(G.) Glasgow Search for other works by this author on: Oxford Academic Google Scholar J. B. MACMILLAN, M.B., F.R.F.P.S.(G.) J. B. MACMILLAN, M.B., F.R.F.P.S.(G.) Glasgow Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 64, Issue 12, 1 December 1952, Pages 442–446, https://doi.org/10.1111/j.1365-2133.1952.tb15881.x Published: 01 December 1952