tbuckley/cabot-search huggingface dataset:
Motilin release in the pig.
Authors: I M Modlin, P Mitznegg, S R Bloom
Journal: Gut (1978)

Motilin is found in the upper intestine of pig and man and in man is released by acid. A similar release by acid has now been found in the pig and is associated with markedly reduced immunostainable motilin in the upper small intestine. Clamping the arteries and veins to the stimulated segment immediately reversed the rise of plasma motilin, indicating the motilin release to be an entirely local phenomenon. The apparent half life of endogenous motilin was 3.9 minutes. No release of motilin was seen after a meal and the possible physiological role of motilin thus remains speculative.
Professional teams who deal with young offenders lack healthcare expertise
Authors: Roger Dobson
Journal: BMJ (2006)

Many young offenders in England and Wales lack adequate access to health care, a new report says. 

One in three youth offending teams, the multiagency groups designed to bring together education, health, and social care professionals, as well as the police and probation services, does not have a mental health worker, says the report from the Healthcare Commission and Her Majesty's Inspectorate of Probation. 

And it says that a sixth of the teams do not have a healthcare worker, although primary care trusts have a statutory duty to provide one …
Poly (ADP-ribose) polymerase-1 is a key mediator of liver inflammation and fibrosis
Authors: Partha Mukhopadhyay, Mohanraj Rajesh, Zongxian Cao, Béla Horváth, Ogyi Park, Hua Wang, Katalin Erdelyi, Eileen Holovac, Yuping Wang, Lucas Liaudet, Nabila Hamdaoui, Fouad Lafdil, György Haskó, Csaba Szabo, Hamid A. Boulares, Bin Gao, Pal Pacher
Journal: Hepatology (2013)

Poly (ADP-ribose) polymerase 1 (PARP-1) is a constitutive enzyme, the major isoform of the PARP family, which is involved in the regulation of DNA repair, cell death, metabolism, and inflammatory responses. Pharmacological inhibitors of PARP provide significant therapeutic benefits in various preclinical disease models associated with tissue injury and inflammation. However, our understanding the role of PARP activation in the pathophysiology of liver inflammation and fibrosis is limited. In this study we investigated the role of PARP-1 in liver inflammation and fibrosis using acute and chronic models of carbon tetrachloride (CCl4)-induced liver injury and fibrosis, a model of bile duct ligation (BDL)-induced hepatic fibrosis in vivo , and isolated liver-derived cells ex vivo . Pharmacological inhibition of PARP with structurally distinct inhibitors or genetic deletion of PARP-1 markedly attenuated CCl4-induced hepatocyte death, inflammation, and fibrosis. Interestingly, the chronic CCl4-induced liver injury was also characterized by mitochondrial dysfunction and dysregulation of numerous genes involved in metabolism. Most of these pathological changes were attenuated by PARP inhibitors. PARP inhibition not only prevented CCl4-induced chronic liver inflammation and fibrosis, but was also able to reverse these pathological processes. PARP inhibitors also attenuated the development of BDL-induced hepatic fibrosis in mice. In liver biopsies of subjects with alcoholic or hepatitis B-induced cirrhosis, increased nitrative stress and PARP activation was noted. Conclusion : The reactive oxygen/nitrogen species-PARP pathway plays a pathogenetic role in the development of liver inflammation, metabolism, and fibrosis. PARP inhibitors are currently in clinical trials for oncological indications, and the current results indicate that liver inflammation and liver fibrosis may be additional clinical indications where PARP inhibition may be of translational potential. (Hepatology 2014;59:1998–2009)
An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice
Authors: Brian C. Tieu, Chang Lee, Hong Sun, Wanda LeJeune, Adrian Recinos, Xiaoxi Ju, Heidi Spratt, Dong-Chuan Guo, Dianna Milewicz, Ronald G. Tilton, Allan R. Brasier
Journal: Journal of Clinical Investigation (2009)

Vascular inflammation contributes to cardiovascular diseases such as aortic aneurysm and dissection. However, the precise inflammatory pathways involved have not been clearly defined. We have shown here that subcutaneous infusion of Ang II, a vasopressor known to promote vascular inflammation, into older C57BL/6J mice induced aortic production of the proinflammatory cytokine IL-6 and the monocyte chemoattractant MCP-1. Production of these factors occurred predominantly in the tunica adventitia, along with macrophage recruitment, adventitial expansion, and development of thoracic and suprarenal aortic dissections. In contrast, a reduced incidence of dissections was observed after Ang II infusion into mice lacking either IL-6 or the MCP-1 receptor CCR2. Further analysis revealed that Ang II induced CCR2+CD14hiCD11bhiF4/80- macrophage accumulation selectively in aortic dissections and not in aortas from Il6-/- mice. Adoptive transfer of Ccr2+/+ monocytes into Ccr2-/- mice resulted in selective monocyte uptake into the ascending and suprarenal aorta in regions of enhanced ROS stress, with restoration of IL-6 secretion and increased incidence of dissection. In vitro, coculture of monocytes and aortic adventitial fibroblasts produced MCP-1- and IL-6-enriched conditioned medium that promoted differentiation of monocytes into macrophages, induced CD14 and CD11b upregulation, and induced MCP-1 and MMP-9 expression. These results suggest that leukocyte-fibroblast interactions in the aortic adventitia potentiate IL-6 production, inducing local monocyte recruitment and activation, thereby promoting MCP-1 secretion, vascular inflammation, ECM remodeling, and aortic destabilization.
Lithium Carbonate Treatment of Mania Associated With Klinefelter's Syndrome
Authors: Oliver G. Cameron, Stephen G. Landau
Journal: JAMA (1980)

To the Editor.—  Although manic symptoms are commonly believed to be the specific manifestation of the primary affective disorder mania, they may be associated with and often are secondary to other causes. 1 For example, Caroff 2 described a patient with Klinefelter's syndrome and bipolar affective illness and noted that at least eight other such cases appear in the literature (although with variable rigor of diagnostic documentation). We wish to report another such case, to alert physicians to the possibility of this association, and to suggest that the use of lithium carbonate may be appropriate and effective in this as well as other situations in which mania-like mental status changes are associated with or secondary to other causes (241:1011, 1979).  Report of a Case.—  A 25-year-old marriedn man with no prior psychiatric history was hospitalized in April 1974. For three weeks his family had noted him to be verbose, grandiose,
CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease
Authors: Maurice G. Emery, Jeannine M. Fisher, Jenny Y. Chien, Evan D. Kharasch, Patchen E. Dellinger, Kris V. Kowdley, Kenneth E. Thummel
Journal: Hepatology (2003)

Previous studies suggest that hepatic cytochrome P450 2E1 (CYP2E1) activity is increased in individuals with chronic alcoholism, nonalcoholic steatohepatitis (NASH), and morbid obesity, and may contribute to liver disease. We studied 16 morbidly obese subjects with varying degrees of hepatic steatosis and 16 normal-weight controls. Obese subjects were evaluated at baseline, 6 weeks, and 1 year after gastroplasty, a procedure that leads to weight loss. Hepatic CYP2E1 activity was assessed by determination of the clearance of chlorzoxazone (CLZ), an in vivo CYP2E1-selective probe. Liver biopsy tissue was obtained during surgery for histopathology. Both the total and unbound oral CLZ clearance (Cl(u)/F) was elevated approximately threefold in morbidly obese subjects compared with controls (P <.001). The Cl(u)/F was significantly higher among subjects with steatosis involving >50% of hepatocytes, compared with those with steatosis in < or =50% of hepatocytes (P =.02). At postoperative week 6 and year 1, the median body mass index (BMI) of subjects who underwent gastroplasty decreased by 11% and 33%, total oral CLZ clearance declined by 16% (P <.01) and 46% (P <.05), and Cl(u)/F decreased by 18% (P <.05) and 35% (P =.16), respectively. Moreover, those subjects with a year 1 BMI <30 kg/m(2) exhibited a median Cl(u)/F that was 63% lower (P =.02) than the respective clearance for all other subjects. In conclusion, hepatic CYP2E1 activity is up-regulated in morbidly obese subjects. A positive association between the degree of steatosis and CYP2E1 activity preoperatively and between the extent of obesity and CYP2E1 activity postoperatively, suggests that CYP2E1 induction is related to or caused by hepatic pathology that results from morbid obesity.
Challenge to the City Hospitals
Authors: Michael L. Glenn
Journal: New England Journal of Medicine (1966)

EMERGENCY and outpatient treatment has continued to perplex American hospitals. Emergency rooms are packed with "nonurgent"1 patients. Costs per visit soar, increasing the deficit of dealing with the indigent2; outpatient visits increase by 20 per cent in one decade.3 Medical education becomes sandwiched between the burden of handling the community's sick and the pressures of research. And hospital planning and reform seem to move slowly.These problems are acutely felt in the large city hospital affiliated with a university teaching center. The young house officer soon realizes that he is operating in a matrix whose determinants are the patients, . . .
1085. Directed Evolution of AAV2 Leads to Improved Viral Function
Authors: James T. Koerber, Narendra Maheshri, Brian Kaspar, David V. Schaffer
Journal: Molecular Therapy (2005)

Adeno-associated viral (AAV) vectors are extremely safe and efficient gene delivery vehicles. However, numerous challenges in vector design remain, including neutralizing antibody responses, tissue transport, and infection of resistant cell types. In each case, the AAV capsid structure determines how the vector performs when presented with these barriers. Nature has evolved multiple AAV serotypes using mutagenesis and recombination, indicating a natural level of plasticity in viral structure and function. We have employed analogous techniques to rapidly generate a large random mutant AAV2 library and have selected for mutant AAV virions that display novel phenotypes. Specifically, we have selected the AAV2 library for infectious particles with altered heparin sulfate (HS) affinity and for the ability to evade an AAV2 immune response. Characterization of the mutants with both lower and higher affinity to heparin led to the location of novel point mutations on the capsid structure. Several of these mutations lie inside the capsid while two exposed mutations (K258E and S261F) lie in the canyon region. Furthermore, we have evolved vector variants that have greater than 100-fold improved resistance to serum that neutralizes wild type AAV2, yet retain AAV2 gene delivery efficiency. Analysis of the point mutations revealed one change on the surface of the 3-fold spike (N587I) and another change on the 2-fold dimple region (T716A) were critical to the enhanced resistance. Testing these vectors in animal studies may indicate that they could mediate gene delivery even in patients with pre-existing immunity. Finally, our libraries can be further analyzed to isolate mutants that surpass other barriers to successful gene delivery.
Inverse correlation between the titre of antibody to hepatitis C virus and the degree of hepatitis C viraemia
Authors: Eriko Yoshimura, Jun Hayashi, Yoshiki Tani, Misako Ohmiya, Koya Nakashima, Hideyuki Ikematsu, Naoko Kinukawa, Yoshiaki Maeda, Seizaburo Kashiwagi
Journal: Journal of Infection (1994)
Spinal cord injuries in rugby union players
Authors: T. Noakes, I. Jakoet
Journal: BMJ (1995)

Recognition nearly 20 years ago of a high incidence of spinal cord injuries in rugby union players1 led eventually to changes in the rules in most rugby playing countries. New Zealand changed its rules in 1980 and 1984; Britain in 1979, 1984, and 1985; Australia in 1985; and South Africa in 1990. The consensus is that these changes have produced the desired effect, but how robust is the evidence? The week in which the Rugby World Cup begins in South Africa seems an apt time to address this question.

Silver's study of 63 spinal cord injuries in rugby union players between 1952 and 1982 was important in identifying mechanisms of injury in a representative sample of rugby players.2 But it was not a study of incidence. Two further studies by him included all spinal cord injuries in rugby players treated in eight spinal units in England and Wales between 1980 and 1986.3 4 By this time the incidence of spinal cord injuries should have begun to fall if the actions taken by the English Rugby Football Union had been effective.

These data show that, although the annual incidence of spinal cord injuries at Stoke Mandeville Hospital fell steadily from a peak of …
Prevalence, concentration, and prognostic importance of proteinuria in patients with malignancies
Authors: N. Sawyer, J. Wadsworth, M. Wijnen, R. Gabriel
Journal: BMJ (1988)

Protein was found significantly more frequently in single urine samples from 504 patients with malignancy (290; 58%) than in 529 controls (119; 22%) (p less than 0.01). Median protein concentration was greater (p less than 0.001) in patients with neoplasia (0.14 g/l) than in controls (0.07 g/l). Actuarial analysis showed a median survival of 4.5 months in patients with proteinuria compared with 10 months in those without (p less than 0.001). The association between proteinuria and shorter survival was statistically significant for patients with gut tumours, lung tumours, and tumours at other sites analysed as a group. Patients with myeloma or urinary tract tumours were not studied. In many patients with malignancy the presence of proteinuria may be associated with a substantially reduced survival time.
Abstract 5069: Comprehensive mutational analysis of epidermal growth factor receptor, EML4-ALK, and KRAS identifies four distinct disease entity in never-smoker patients with non-small cell lung cancer
Authors: Hye Ryun Kim, Hyo Sup Shim, Jin-Haeng Chung, Young Joo Lee, Sang-Jun Ha, Se Kyu Kim, Joo Hang Kim, Byoung Chul Cho
Journal: Cancer Research (2011)

Abstract Purpose: To determine the proportions of major oncogenic mutations and examine the survival in genotype-specific subsets in non-small-cell lung cancer (NSCLC) from never-smokers. Patients and Methods: We concurrently analyzed mutations in epidermal growth factor receptor (EGFR), EML4-ALK, and KRAS in 229 never-smokers with NSCLC. The ALK rearrangements was identified by using fluorescent in situ hybridization and confirmed by immunohistochemistry. The EGFR (exons 18 to 21) and KRAS (codon 12/13) mutations were determined by direct sequencing. Results: Of 229 tumors, the frequency of EGFR mutation, ALK rearrangement, KRAS mutation, and wild-type for aforementioned genes (WT/WT/WT) were 48.0%, 8.3%, 3.5%, and 40.2%. All mutations were mutually exclusive. The progression free survival to EGFR tyrosine kinase inhibitors (TKIs) was 12.8, 6.3, 2.1, and 1.6 months in EGFR mutant, WT/WT/WT, KRAS mutant, and EML4-ALK, respectively. In a logistic regression model, the adjusted hazard ratio for the risk of disease progression to EGFR TKIs was 0.59 (95% CI, 0.40 to 0.87; P = .008) for EGFR mutant, 4.58 (95% CI, 2.07 to 10.15; P &amp;lt; .001) for EML4-ALK, 4.23 (95% CI, 1.65 to 10.8; P &amp;lt; .003) for KRAS mutant, respectively. Overall survival was also significantly different among genotypes. Conclusion: This is the first comprehensive and concurrent analysis of three major oncogenic mutations in the largest-ever cohort of East Asian never-smokers with NSCLC. Since survival outcome is different among genotypes and drugs are now available to target these mutations, genetic profiling is needed to identify genotype-specific subsets and successfully treat them with appropriate kinase inhibitors. 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 5069. doi:10.1158/1538-7445.AM2011-5069
Points from Letters: Review Body's Report
Authors: P. Keppich
Journal: BMJ (1966)

Registrars' Pay SIR,-I have read with interest, and no small degree of irritation, the 'expected correspondence and the reports of meetings in the B.M.7.following the publication of the Review Body's findings.As a member of the much despised grade of medical assistant who is quite happy with his lot and has no intention of leaving the country, I am sick and tired of
Smoking and the risk of diabetes in elderly Finnish men. Retrospective analysis of data from a 30-year follow-up study.
Authors: Q Qiao, T Valle, A Nissinen, J Tuomilehto
Journal: Diabetes Care (1999)

To assess the association of smoking with the risk of glucose intolerance (diabetes plus impaired glucose tolerance).A cohort consisting of 1,711 Finnish men born in 1900-1919 were followed up from 1959 to 1994. Smoking status was assessed in a similar way at each of the six surveys from 1959 to 1989, and subjects were classified as never, former, or current smokers. Diagnosis of diabetes and impaired glucose tolerance was made according to the oral glucose tolerance tests made in 1984 and 1989, and the 1985 World Health Organization criteria was applied.Association between smoking and glucose intolerance was estimated separately for 420 participants and 243 nonparticipants in 1989. Multiple logistic regression analyses show that odds ratios of glucose intolerance in 1984 for current smokers in 1984 were 0.36 (0.19-0.70) and 1.20 (0.52-2.78), respectively, in the participants and the nonparticipants in 1989. Among the nonparticipants in 1989, the odds ratio for current smokers in 1969 was 2.23 (1.00-4.96). A reduced risk of glucose intolerance in 1989 associated with smoking in the participants in 1989 was found to be significant from the beginning of the follow-up. The participants in 1989 were generally healthier and had a longer life expectancy than the nonparticipants in 1989.In a retrospective study of men, an increased risk of diabetes and impaired glucose tolerance in smokers was found among the nonparticipants, but a reduced risk was found among the participants in 1989. The difference observed might be attributed to the fact that the participants were constitutionally different from the nonparticipants.
BMA wants presumed consent for organ donors
Authors: L. Beecham
Journal: BMJ (1999)

The BMA will lobby the government to introduce a system of “presumed consent” for organ donation under which doctors will be allowed to assume that all patients are willing to have their organs removed after death unless they have registered their objection beforehand.

Representatives at last week's meeting of the BMA's annual meeting in Belfast voted overwhelmingly in favour of an opt- out system, a change in the policy that it has held for nearly 30 years. They also called for a public education campaign about …
Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China.
Authors: A P Avolio, F Q Deng, W Q Li, Y F Luo, Z D Huang, L F Xing, M F O'Rourke
Journal: Circulation (1985)

Arterial pulse wave velocity, an established index of arterial distensibility, was measured together with arterial pressure in a group of 524 normal subjects of both sexes 2 months to 94 years old (mean age 45.6 +/- 15.3 years [SD]) in rural Guangzhou, China, an area with known low prevalence of hypertension. Fasting serum lipid levels and overnight Na+ and K+ urinary excretion levels were determined in a subgroup of 104 subjects (ages 8 to 88 years). Comparisons were made with data obtained similarly from normal subjects in urban Beijing, an area with known high prevalence of hypertension. Serum cholesterol levels were similar and low in each group (Guangzhou, 4.34 +/- 0.12 mmol/liter [SE]; BEijing, 4.49 +/- 0.11 mmol/liter). Prevalence of hypertension (WHO criteria) was 4.9% (Guangzhou) and 15.6% (Beijing). In Guangzhou subjects pulse wave velocity was consistently lower in the aorta, arm, and leg, and increased to a lesser degree with age compared with Beijing subjects. Regression equations (x = pulse wave velocity [cm/sec], y = age [years]) were as follows: (1) aorta, Guangzhou: y = 5.1x + 533, r = .552, p less than .05; Beijing: y = 9.2x + 615, r = .673, p less than .001; (2) arm, Guangzhou: y = 0.61x + 817, r = .121, p less than .05; Beijing: y = 4.8x + 998, r = .453, p less than .001; (3) leg, Guangzhou: y = 4.43x + 718, r = .512, p less than .05; Beijing: y = 5.6x + 791, r = .630, p less than .001.(ABSTRACT TRUNCATED AT 250 WORDS)
Rib Artifact Demonstrated on Xenon-133 Lung Imaging
Authors: TIMOTHY S. BURKE, JAMES L. TATUM, MELVIN J. FRATKIN
Journal: Clinical Nuclear Medicine (1987)

Xenon-133 imaging requires the pulse height analyzer (PHA) to be centered on the 81 kev gamma photon emission. Peaking the PHA on a low energy emission may cause an attenuation artifact, as shown in this report.
CHEMICAL AND IMMUNOLOGICAL PROPERTIES OF A SPECIES-SPECIFIC CARBOHYDRATE OF PNEUMOCOCCI
Authors: William S. Tillett, Walther F. Goebel, Oswald T. Avery
Journal: The Journal of Experimental Medicine (1930)

Pneumococci contain a non-protein constituent which, on the basis of its chemical and immunological properties, appears to be a carbohydrate distinct from the type-specific carbohydrate and common to the species.