tbuckley/cabot-search huggingface dataset:
SAD Kinases Sculpt Axonal Arbors of Sensory Neurons through Long- and Short-Term Responses to Neurotrophin Signals
Authors: Brendan N. Lilley, Y. Albert Pan, Joshua R. Sanes
Journal: Neuron (2013)

Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A, and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here, we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short-duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short-duration signals from extrinsic cues to sculpt axon arbors within the CNS.
Mortality on Mount Everest, 1921-2006: descriptive study
Authors: P. G Firth, H. Zheng, J. S Windsor, A. I Sutherland, C. H Imray, G W K Moore, J. L Semple, R. C Roach, R. A Salisbury
Journal: BMJ (2008)

To examine patterns of mortality among climbers on Mount Everest over an 86 year period.Descriptive study.Climbing expeditions to Mount Everest, 1921-2006.14,138 mountaineers; 8030 climbers and 6108 sherpas.Circumstances of deaths.The mortality rate among mountaineers above base camp was 1.3%. Deaths could be classified as involving trauma (objective hazards or falls, n=113), as non-traumatic (high altitude illness, hypothermia, or sudden death, n=52), or as a disappearance (body never found, n=27). During the spring climbing seasons from 1982 to 2006, 82.3% of deaths of climbers occurred during an attempt at reaching the summit. The death rate during all descents via standard routes was higher for climbers than for sherpas (2.7% (43/1585) v 0.4% (5/1231), P<0.001; all mountaineers 1.9%). Of 94 mountaineers who died after climbing above 8000 m, 53 (56%) died during descent from the summit, 16 (17%) after turning back, 9 (10%) during the ascent, 4 (5%) before leaving the final camp, and for 12 (13%) the stage of the summit bid was unknown. The median time to reach the summit via standard routes was earlier for survivors than for non-survivors (0900-0959 v 1300-1359, P<0.001). Profound fatigue (n=34), cognitive changes (n=21), and ataxia (n=12) were the commonest symptoms reported in non-survivors, whereas respiratory distress (n=5), headache (n=0), and nausea or vomiting (n=3) were rarely described.Debilitating symptoms consistent with high altitude cerebral oedema commonly present during descent from the summit of Mount Everest. Profound fatigue and late times in reaching the summit are early features associated with subsequent death.
Interaction of desialated guinea pig erythrocytes with the classical and alternative pathways of guinea pig complement in vivo and in vitro.
Authors: E J Brown, K A Joiner, M M Frank
Journal: Journal of Clinical Investigation (1983)

We examined the fate of desialated autologous erythrocytes injected intravenously into guinea pigs (GP). Desialated GP erythrocytes (E) were lysed directly or cleared by the reticuloendothelial system in normal GP (NIH-GP) and cleared by the reticuloendothelial system in GP genetically deficient in the classical complement pathway component C4 (C4D-GP), which activate complement only via the alternative pathway. Desialated E were also cleared in cobra venom factor-treated GP (CVF-GP), which had less than 1% of normal C3 levels, but were not cleared at all in C4D-CVF-GP. Preinjection of asialoorosomucoid (ASOR) and ovalbumin (OVA) had no effect on the rate of E clearance. These in vivo studies indicated that complement activation is essential for clearance of desialated E and that clearance is unaffected by blockade of galactose or mannose receptors. Inhibition of complement-mediated clearance required blockade of both classical and alternative complement pathways. In vitro studies showed that lysis of desialated E could occur in NIH-GP serum (GPS) but not in C4D-GPS. Surprisingly, CVF-GPS also caused lysis of desialated E. Lysis was dependent on both natural antibody to desialated E and classical pathway activation; natural antibody was of both the IgG and IgM classes. C3 uptake studies demonstrated that almost 10 times as many C3 molecules/E were deposited by NIH-GPS as by C4D-GPS or CVF-GPS onto desialated E. Approximately equal numbers of C3 molecules were deposited by CVF-GPS, which did lyse desialated E, and by C4D-GPS, which did not. We suggest that the molecular mechanism of in vivo clearance and in vitro lysis of desialated E by CVF-GP is via classical pathway deposition of C3b into sites on the erythrocyte surface protected from inactivation by H (beta 1H) and I (C4b/3b inactivator). Deposition of C3b into these sites by alternative pathway activation is sufficient to cause clearance but not lysis of desialated E. CVF-GPS may not represent an adequate reagent for testing the complement dependence of various biologic phenomena, particularly if the question involves surfaces that can provide protected sites for C3b molecules.
Conversion to Problem-Oriented Records in an Established Practice
Authors: JACK FROOM
Journal: Annals of Internal Medicine (1973)

A change to problem-oriented records was initiated in a 21-year-old solo primary practice generally limited to nonsurgical adult medical patients. The change was valuable because it produced a critical review of patients' problems. Important but neglected clinical data were unearthed. Three hundred charts were reviewed in depth, and complete problem sheets were constructed. An average of 6.4 minutes was necessary for each chart, but the median time for conversion of charts was slightly less than 5 minutes. An average of two charts were reviewed in each half-day office session. A change to problem-oriented records can be accomplished with a modest expenditure of time and effort, even in a busy established practice.
732 ALTERATIONS IN HYPPOCAMPAL AND TALAMIC ACETYLCHOLINESTERASE LEVELS RELATED WITH HEPATIC ENCEPHALOPATHY IN CIRRHOTIC RATS
Authors: M.-A. Aller, M. Mendez, M. Méndez-López, L. López, I. Prieto, J. Arias, J.-L. Arias
Journal: Journal of Hepatology (2009)
Fukushima Health Study Launched
Authors: Winifred A. Bird
Journal: Environmental Health Perspectives (2011)

Forum Perc Clings to Dry-Cleaned ClothesA new study finds that the solvent perchlor ethylene, or "perc," can accumulate in dry cleaned clothes over repeated cleanings, building up the most in wool, cotton, and polyester; silk was largely unaffected. 1 Occupational exposures to perc, used by 65-70% of the estimated 25,000 dry cleaners in the United States, 2 have been linked to numerous adverse health effects.The study did not determine whether the levels found present a definite health risk, but the authors conclude they could lead to indoor air levels that exceed government recommendations.
Abstract 1002: Norrin controls colon cancer angiogenesis
Authors: Kestutis Planutis, Marina Planoutene, Randall F. Holcombe
Journal: Cancer Research (2014)

Abstract The purposes of the study: Colorectal (CRC) tumors depend on mediators in the tumor microenvironment, such as vascular endothelial growth factor, to promote angiogenesis. Norrin is a ligand that binds to the cell surface Frizzled-4 receptor, stimulating canonical Wnt signaling, and is known to mediate blood vessel growth in the eye and ear. We investigate here the role of Norrin secreted by colon cancer cells in endothelial cell growth and motility as well as the expression of the Norrin signaling pathway components in the CRC tumor microenvironment. Experimental procedures: Primary human umbilical vein endothelial cells (HUVEC) expressing green fluorescent protein and a HUVEC-derived endothelial cell line, EAhy926 were utilized for in vitro angiogenesis assays measuring cell motility and in vitro angiogenesis. Experiments were performed with and without the addition of Norrin-containing conditioned medium from a transfected CRC cell line CaCO2 and with and without blocking anti-Norrin antibodies. Tissue specimens from human CRC patients were evaluated with a double signal amplification system to define the expression of Norrin, Frizzled-4, LRP5 and TSPAN12 in tumor blood vessels. Summary of data: Blocking generated by the endothelial cells themselves Norrin reduced endothelial cell motility, branch point number during in vitro angiogenesis (1/sq. mm), and the network length (mm/sq. mm) during in vitro angiogenesis. Norrin conditioned medium produced by CRC cell line CaCO2 transfected with Norrin expression construct increased endothelial cell motility. Colorectal tumors express Norrin protein. Endothelial cells in the colorectal tumor blood vessels contain all of the components of the Norrin signaling pathway needed for the endothelial cells to respond to Norrin in the tumor microenvironment. Statement of the conclusions: This study presents both in vitro and in vivo data that colorectal tumors use Norrin protein as an alternative mechanism that promotes angiogenesis in the CRC tumor microenvironment. Citation Format: Kestutis Planutis, Marina Planoutene, Randall F. Holcombe. Norrin controls colon cancer angiogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1002. doi:10.1158/1538-7445.AM2014-1002
Oral contraception in patients with hyperprolactinaemia.
Authors: P J Moult, J E Dacie, L H Rees, G M Besser
Journal: BMJ (1982)

decreasing temperature.Cardiac massage at a reduced rate is the usual treatment in such cases.In contrast, Niazi and Lewis' described one hour of asystole at 9°C in controlled hypothermia; their patient reattained spontaneous sinus rhythm during superficial rewarming.Our patient was ventilated as if he were normothermic, thus generating alkalosis.This is controversial2 but has been advocated by some clinical investigators.3He had asystole on arrival at hospital.It is not clear when this began, but serious arrhythmias may occur when hypothermic patients are handled-for example, when they are lifted on to or from stretchers.The initial drop in temperature that occurred in our case is a wellknown phenomenon when superficial rewarming is used and should not discourage staff from continuing the resuscitation.Core rewarming requires trained staff and more expensive and sophisticated equipment such as a heart-lung machine, peritoneal dialysis, and peritoneal lavage.This case supports previous suggestions4 5 that in the treatment of accidental hypothermia successful results may be attained without resort to sophisticated equipment.
Need for Continued Oral Therapy in Diabetes
Authors: J. W. Todd
Journal: BMJ (1972)

suspected until a few months before death when increased pain necessitated surgery.All these patients had severe anaemia (Hb 55-60%) at diagnosis.All had a longstanding history of duodenal ulcer and were then found to have gastric cancer.It seems, therefore, that such cases need very careful examination if they come to operation for a duodenal ulcer.Tragically, all were late diagnoses chiefly because dyspeptic symp- toms were wrongly interpreted in the 16-12 months before laparotomy.It is said that duodenal ulcer and gastric cancer only rarely coexist,' and a report from the Birmingham Regional Cancer Registry and the United Birmingham Hos- pitals stated that no association was found between cancer and peptic ulcer.2-Iam, etc.,
Controlled Trial of Prednisone in Adult Patients with the Nephrotic Syndrome
Authors: D. A. K. Black, G. Rose, D. B. Brewer
Journal: BMJ (1970)

A multi-centre controlled trial of steroid treatment of the nephrotic syndrome was carried out on 125 patients. Of these, 64 were controls and 61 received prednisone in a recommended dose range of 20-30 mg./24 hours. The actual initial dose averaged 29 mg./24 hours. Treatment was continued for a variable period, but not less than six months. More than 10 mg./24 hours was given on average for 12 months to all patients, and for longer periods to some. Patients were classified, on the basis of biopsy specimens, into three groups: A, minimal change; B, membranous nephropathy; and C, proliferative glomerulonephritis. In groups B and C prednisone did not have any strikingly favourable effect on proteinuria or on renal function as compared with the control group. In group A, however, prednisone reduced proteinuria to a striking and statistically significant extent. It had little if any effect on long-term renal function in any group. The death rate was higher in the combined prednisone groups (17/61) than in the control groups (12/64). This difference was not statistically significant, but there was a significantly higher number of deaths from cardiovascular disease in the prednisone group, whereas the numbers of deaths from renal failure were not significantly different in the two groups.
HIV Infection in Cuba-Reply
Authors: W. Robert Lange
Journal: JAMA (1987)

In Reply.—  The scope of the AIDS epidemic in Cuba is not accurately known. In 1985, an article appeared in a Cuban medical journal 1 describing what seemed to be a domestic case of AIDS; during the second quarter of 1986, Havana publicly announced what it said was the country's first death due to AIDS. By mid-1987, the reported AIDS caseload had grown to three, giving this nation of more than 10.1 million residents the lowest attack rate of regions reporting AIDS in the western hemisphere. Many believe that the number of cases in Cuba has been misrepresented, and there are a variety of circumstances that support the contention that the AIDS situation in Cuba is more serious than has been admitted.  The deployment of Cuban troops to Angola has afforded the opportunity for military personnel not only to become exposed to HIV, but to bring the virus back to
CHEMICAL BASIS FOR AN IMMUNOLOGICAL SPECIFICITY OF A STRAIN OF STAPHYLOCOCCUS AUREUS
Authors: William G. Juergens, Arnold R. Sanderson, Jack L. Strominger
Journal: The Journal of Experimental Medicine (1963)

Antisera, prepared against formalin-killed cells of Staphylococcus aureus, strain Copenhagen, agglutinated the cell walls of this strain. The agglutination was inhibited by the teichoic acid from the cell wall of this strain, by any degradation product of this teichoic acid which contained the alpha-acetylglucosaminyl-ribitol unit, by alpha-phenyl-acetylglucosaminide, and by N-acetylglucosamine, but not by a large number of other haptens related to the cell wall. In quantitative experiments, however, only 40 to 50 per cent of antibody adsorption to cell wall could be inhibited by teichoic acid or by N-acetylglucosamine. The alpha-acetylglucosaminyl-ribitol unit in the teichoic acid is, therefore, an important immunological determinant in the cell wall of this strain, although other immunological specificities may also exist. The cell walls were also agglutinated by heterologous antisera prepared against streptococcal Group A carbohydrate or against horse serum azophenyl-beta-acetylglucosaminide. The heterologous agglutination, however, was specific for the beta-acetylglucosaminyl-ribitol units in the teichoic acid.
S-nitrosocysteine inhibition of human platelet secretion is correlated with increases in platelet cGMP levels.
Authors: E H Lieberman, S O'Neill, M E Mendelsohn
Journal: Circulation Research (1991)

Platelet inhibition by exogenous and endogenous nitrovasodilators has been shown to be associated with increases in cGMP, but proof of a role for cGMP in this process is lacking. We therefore studied the effects of cGMP and guanylate cyclase stimulation on human platelet secretion by pharmacologically modulating intraplatelet cGMP levels. The endothelium-derived relaxing factor (EDRF)-like activator of guanylate cyclase, S-nitrosocysteine (SNOC), led to a dose-dependent inhibition of secretion in intact human platelets (IC50 = 10(-6) M). The cGMP phosphodiesterase inhibitor M&amp;B 22,948 augmented SNOC-induced inhibition of secretion through elevations in cGMP without affecting cAMP levels (from 50% to 81% inhibition versus control, p = 0.02). Methylene blue reversed the inhibitory effects of SNOC on platelet secretion (p = 0.03). Dibutyryl-cGMP and 8-bromo-cGMP also significantly inhibited secretion in this system. Incubation of platelets with exogenous cGMP to achieve intraplatelet cGMP levels comparable to those after SNOC treatment resulted in similar degrees of inhibition of secretion (32% inhibition versus control, p = 0.01) and was also potentiated by M&amp;B 22,948 (from 32% to 68% inhibition, p = 0.003). In addition, a highly significant correlation between intraplatelet cGMP levels and the degree of inhibition of secretion was demonstrable in these studies (r = 0.94, p = 0.016). These data demonstrate that elevation of intraplatelet cGMP levels by the EDRF-like compound SNOC is correlated with inhibition of human platelet secretion.
Fully covered self-expanding metal stents for benign colonic strictures
Authors: G. Vanbiervliet, P. Bichard, J.-F. Demarquay, E. Ben-soussan, S. Lecleire, K. Barange, J.-M. Canard, H. Lamouliatte, E. Fontas, M. Barthet, T. Ponchon, J.-C. Saurin
Journal: Endoscopy (2012)

<b>Background and study aims:</b> Uncovered self-expanding metal stents offer effective relief for colonic obstruction. The aim of this study was to determine the effectiveness of fully covered self-expanding metal stents (FCSEMSs) in the treatment of benign colonic strictures. <b>Patients and methods:</b> All patients presenting with a symptomatic benign colonic stricture (occlusion or subocclusion) during a 6-year study period were treated with FCSEMSs. The stents were placed and removed 4 – 6 weeks later at one of 10 endoscopy centers. The efficacy of the stent (clinical and radiological signs of colonic decompression within 48 hours), technical success, stent retrieval, safety, and recurrence of symptoms were evaluated during follow-up. Univariate and multivariate analyses were performed to identify variables associated with clinical success, stent migration, and symptom recurrence. <b>Results:</b> The study included 43 patients (24 men, 19 women; mean age 67.6 ± 10.4) with occlusive (n = 18) or subocclusive symptoms (n = 25) due to anastomotic (n = 40), post-ischemic (n = 2), or post-radiation (n = 1) strictures. Insertion was successful in all patients. Clinical success was obtained in 35 patients (81 %). Migration was observed in 27 patients (63 %). The median duration of stenting was 21 days (95 %CI 17.8 – 35.4 days). Multivariate analysis showed that stents more than 20 mm wide migrated significantly less often. Recurrence of obstructive symptoms was observed in 23 patients (53 %), irrespective of migration. No predictive factors for recurrence or clinical efficacy were found. <b>Conclusions:</b> FCSEMSs for treatment of symptomatic benign colonic strictures are safe and effective, despite a high rate of spontaneous migration.
Long-term outcomes of endoscopic submucosal dissection for undifferentiated-type early gastric cancer
Authors: K. Okada, J. Fujisaki, T. Yoshida, H. Ishikawa, T. Suganuma, A. Kasuga, M. Omae, M. Kubota, A. Ishiyama, T. Hirasawa, A. Chino, M. Inamori, Y. Yamamoto, N. Yamamoto, T. Tsuchida, Y. Tamegai, A. Nakajima, E. Hoshino, M. Igarashi
Journal: Endoscopy (2012)

Endoscopic submucosal dissection (ESD) of undifferentiated-type early gastric cancer (UD-EGC) is technically feasible; however, the long-term clinical outcomes of the procedure have not yet been fully investigated. The aim of our study was to elucidate long-term outcomes of ESD for UD-EGC.Between September 2003 and October 2009, a total of 153 patients were diagnosed endoscopically as having UD-EGC fulfilling the expanded criteria for ESD. After informed consent was obtained, 101 patients were selected to undergo ESD and 52 to undergo surgical operation. We assessed the clinical outcomes of ESD in 101 consecutive patients with 103 UD-EGC lesions who were undergoing ESD for the first time. The overall mortality and disease-free survival rates after ESD were evaluated as the long-term outcomes.The rates of en bloc and curative resection were 99.0% (102/103) and 82.5% (85/103), respectively. We encountered one patient with nodal metastasis detected by computed tomography before diagnostic ESD, although curative resection of the primary lesion was achieved based on routine histological examination. Among the 78 patients without a past history of malignancy within the previous 5 years in whom curative resection of the primary lesion was achieved, no cases of local recurrence or distant metastasis were observed during follow-up; however, 1 synchronous and 2 metachronous lesions were detected in 2 patients (2.6%) after primary ESD. Thus, estimated over a median follow-up period of 40.0 months (range 19-92 months) and 36.0 months (range 9-92 months), the 3-and 5-year overall mortality rates were 1.9% and 3.9%, respectively, and the 3-and 5-year overall disease-free survival rates were both 96.7%.Although our single-center retrospective study may be considered to be only preliminary, our data indicate that ESD for UD-EGC may yield good long-term outcomes.
Vertebral osteomyelitis in the elderly
Authors: D Thompson, P Bannister, P Murphy
Journal: BMJ (1988)

Osteomyelitis may be missed in elderly patients with backache when they already have degenerative spinal disease.We report four cases of non-tuberculous vertebral osteomyelitis seen in an acute geriatric unit over 10 years.All four cases were due to infection with Gram negative organisms.An awareness that oestomyelitis has a predominantly non-staphylococcal cause in elderly patients may help in reaching a correct diagnosis. Case reportsThe table sumimarises clinical details of the four patients.Case 1-An 80 year old man was admitted with a one week history of anorexia, vomiting, pain in the right hypochondrium, and fever.His urine was sterile, but cultures of blood grew Escherichia coli.He improved after