tbuckley/cabot-search huggingface dataset:
A multinational pooled analysis of 434 cases of stage I non-small cell lung cancer (NSCLC) treated with volumetrically image-guided (VIGRT) stereotactic lung radiotherapy (SBRT): Results from the Elekta Collaborative Lung Research Group.
Authors: I. S. Grills, A. J. Hope, M. Guckenberger, L. L. Kestin, M. Werner-Wasik, D. Yan, J. Sonke, J. Bissonnette, Y. Xiao, J. Belderbos
Journal: Journal of Clinical Oncology (2010)

7015 Background: Published lung SBRT outcomes/dose response data for inoperable NSCLC come from small phase I-II studies or larger datasets not requiring image-guided radiotherapy (IGRT) or volumetric prescriptions. This entire cohort of SBRT patients had daily online cone-beamCT. Methods: 434 cases of stage I (T1-2N0M0) NSCLC were treated with SBRT via VIGRT at 1 of 5 institutions from 1998-2009. Median age was 74y(42-92); 53% male, 47% female. Median FEV1 was 1.4L(65% predicted); median DLCO was 9.8 ml/min/mmHg(54% predicted). 62% of tumors were biopsy-proven; 84% of cases were staged with CT and PET. Clinical stage was IA in 76%, IB in 22%, locally recurrent in 1%. Median max tumor dimension was 2.4 cm (0.9-8.5cm). Histologies were: 41% adenocarcinoma, 34% squamous, 12% large cell, 13% NSCLC NOS. 8%, 51%, and 42% were grades 1, 2, 3. Median volumetric prescription dose (PD) was 54Gy (20-64Gy) delivered in median of 3 fractions(fx) (1-15fx) over 8d (1-27d). Median biological equivalent PD (BED10) was 132Gy (60-180Gy), equal to 2-Gy fx equivalent (FE) of 110Gy (50-150Gy). Corresponding GTV and PTV mean doses (2-GyFE) were 157Gy and 137Gy. Mean follow-up = 1.3y (0.1-7.3y). Results: 2-y KM rates of local recurrence (LR), regional recurrence (RR) and distant metastasis (DM) were 8%, 13%, and 26%. 2y overall survival (OS) and cause-specific survival (CSS) were 58% and 84%. No statistically significant differences in LR, RR, DM, OS or CSS were identified for biopsied vs. non-biopsied tumors. On univariate analysis, stage (IA 5% v IB 16%, p=0.002), GTV max dimension (<2.7cm 4% v ≥2.7cm 12%, p=0.006), and 2GyFE PD (<88Gy 17% v ≥88Gy 5%, p<0.001) predicted LR. GTV (<115Gy 32% v ≥115Gy 4%, p<0.001) and PTV (<105Gy 24% v ≥105Gy 4%, p<0.001) 2GyFE mean doses also predicted LR. Cox multiple regression confirmed the relationship between PD and LR, independent of GTV size (p=0.01). Conclusions: This is the first Lung SBRT dataset of patients treated uniformly with daily online VIGRT and resulted in excellent local control for stage I NSCLC. A 2-GyFE dose of 88 Gy (BED10 105 Gy) predicted superior local control. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Elekta
Adrenocorticotropin reverses hemorrhagic shock in anesthetized rats through the rapid activation of a vagal anti-inflammatory pathway
Authors: S GUARINI
Journal: Cardiovascular Research (2004)

Several melanocortin peptides have a prompt and sustained resuscitating effect in conditions of hemorrhagic shock. The transcription nuclear factor kappaB (NF-kappaB) triggers a potentially lethal systemic inflammatory response, with marked production of tumor necrosis factor-alpha (TNF-alpha), in hemorrhagic shock. Here we investigated whether the hemorrhagic shock reversal produced by the melanocortin ACTH-(1-24) (adrenocorticotropin) depends on the activation of the recently recognized, vagus nerve-mediated, brain "cholinergic anti-inflammatory pathway".Anesthetized rats were stepwise bled until mean arterial pressure (MAP) stabilized at 20-25 mm Hg. The severe hypovolemia was incompatible with survival, and all saline-treated animals died within 30 min. In rats intravenously (i.v.) treated with ACTH-(1-24), neural efferent activity along vagus nerve (monitored by means of a standard system for extracellular recordings) was markedly increased, and the restoration of cardiovascular and respiratory functions was associated with blunted NF-kappaB activity and with decreased TNF-alpha mRNA liver content and TNF-alpha plasma levels. Bilateral cervical vagotomy, pretreatment with the melanocortin MC(4) receptor antagonist HS014, atropine sulfate or chlorisondamine, but not with atropine methylbromide, prevented the life-saving effect of ACTH-(1-24) and the associated effects on NF-kappaB activity and TNF-alpha levels. HS014 and atropine sulfate prevented, too, the ACTH-(1-24)-induced increase in neural efferent vagal activity, and accelerated the evolution of shock in saline-treated rats.The present data show, for the first time, that the melanocortin ACTH-(1-24) suppresses the NF-kappaB-dependent systemic inflammatory response triggered by hemorrhage, and reverses shock condition, by brain activation (in real-time) of the "cholinergic anti-inflammatory pathway", this pathway seeming to be melanocortin-dependent.
Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension
Authors: Rajeshwar P. Mookerjee, Gautam Mehta, Vairappan Balasubramaniyan, Fatma El Zahraa Mohamed, Nathan Davies, Vikram Sharma, Yasuko Iwakiri, Rajiv Jalan
Journal: Journal of Hepatology (2014)
Ocular Reaction to Foreign Protein
Authors: T. G. W. Parry
Journal: BMJ (1939)

BRITISNa case the diabetes need not be of an " insulin-resistant" type, and would appear to result primarily from the islet lesions.Nevertheless it is possible that such islet lesions might themselves be secondary to a short period of anterior pituitary hyperactivity. SummaryEvidence is given of the significance of the anterior portion of the pituitary gland in the control of carbohydrate metabolism in general, and, in particular, in the* regulation of insulin sensitivity.Many of the effects on carbohydrate metabolism of hypophysectomy and of the administration of anterior pituitary extracts are intimately related.They are here discussed under separate headings.
Altered microbiota in microscopic colitis
Authors: Hans Fischer, Elisabet Holst, Fredrik Karlsson, Cecilia Benoni, Ervin Toth, Martin Olesen, Måns Lindén, Klas Sjöberg
Journal: Gut (2015)

Recently, Shin et al 1 reported that Akkermansia spp had a beneficial effect on glucose homeostasis in obese mice. Mucin degrading Akkermansia —promoting mucin degradation and turnover—is associated with a healthy mucosa. In IBD, a deranged microbiota is reported while findings in microscopic colitis (MC) are lacking. MC is a disorder characterised by chronic non-bloody diarrhoea, predominantly affecting elderly smoking women. Despite frequent diarrhoea, laboratory anomalies are seldom seen.

Since an altered microbiota is reported in several immune mediated diseases and since MC affects the gut, our hypothesis was that the microbiota would be altered in patients with MC.

A group of 10 female patients (mean age 48 years, range 43–68 years) with onset of MC collected as previously described2 donated faecal samples that were compared with samples from seven healthy control women (mean age 50 years, range 45–65 years) with respect to their faecal microbiota.

The bacterial microbiome was analysed by DNA sequencing (Illumina Hiseq 2000) and sequences were aligned to a …
New techniques for early detection of lung cancer
Authors: G. Sutedja
Journal: European Respiratory Journal (2003)

The resurgence of interest in lung cancer screening and the application of new techniques for the management of early cancer have raised various issues regarding this global epidemic. In previous randomised clinical trials, the use of conventional chest radiographs and sputum cytology examinations for screening have been shown not to reduce lung cancer mortality. The use of biomolecular markers, autofluorescence bronchoscopy, low-dose spiral and high-resolution computed tomography, endobronchial ultrasonography, optical coherence tomography, confocal micro-endoscopy, positron emission tomography in combination with video-assisted thoracic surgery and intraluminal bronchoscopic treatments may provide new modalities with which to manage lung cancer at the earliest stage possible. New hopes arise that the combined use of more accurate and minimally invasive diagnostic and treatment techniques may justify screening and reduce mortality. More individuals may also benefit, as many in the target population already suffer from poor cardiovascular and pulmonary health due to their smoking history and are considered at risk for surgical intervention. The cost-effectiveness of lung cancer screening will strongly depend on the proper selection of the target population and the optimal application of these new techniques. Despite epidemiological controversy regarding lung cancer screening, the feasibility to define more precisely who are at risk and the use of less invasive techniques may preserve quality of life and improve the survival of many lung cancer patients.
Biology of Prostate-Specific Antigen
Authors: Steven P. Balk, Yoo-Joung Ko, Glenn J. Bubley
Journal: Journal of Clinical Oncology (2003)

Prostate-specific antigen (PSA) is an androgen-regulated serine protease produced by both prostate epithelial cells and prostate cancer (PCa) and is the most commonly used serum marker for cancer. It is a member of the tissue kallikrein family, some of the members of which are also prostate specific. PSA is a major protein in semen, where its function is to cleave semenogelins in the seminal coagulum. PSA is secreted into prostatic ducts as an inactive 244-amino acid proenzyme (proPSA) that is activated by cleavage of seven N-terminal amino acids. PSA that enters the circulation intact is rapidly bound by protease inhibitors, primarily alpha1-antichymotrypsin, although a fraction is inactivated in the lumen by proteolysis and circulates as free PSA. This proteolytic inactivation, as well as the cleavage of proPSA to PSA, is less efficient in PCa. Serum total PSA levels are increased in PCa, and PSA screening has dramatically altered PCa presentation and management. Unfortunately, although high PSA levels are predictive of advanced PCa, a large fraction of organ-confined cancers present with much lower total PSA values that overlap those levels found in men without PCa. Measurement of free versus total PSA can increase specificity for PCa, and tests under development to measure forms of proPSA may further enhance the ability to detect early-stage PCa. PSA is also widely used to monitor responses to therapy and is under investigation as a therapeutic target. Finally, recent data indicate that there may be additional roles for PSA in the pathogenesis of PCa.
Changes in basement membrane thickness in the human endometrium during the luteal phase of the menstrual cycle
Authors: P Dockery
Journal: Human Reproduction Update (1998)

We have examined aspects of the fine structure of the basal laminae associated with the luminal and glandular epithelium and small blood vessels in the human endometrium. Four short studies are presented and reviewed. Study 1 examined biopsies from 20 fertile women taken on days after the luteinizing hormone surge (LH): LH +2, 4, 6, 8 and 10. The basal lamina (both lamina densa and lucida) increased in thickness over the period studied. Study 2 again studied the glandular epithelium and examined the effect of RU486 (a progesterone receptor blocker) administered on day LH +3 and biopsied on day LH +6. The basal laminae were found to be the same as LH +2 control group but thinner than LH +6 control. Study 3 documented increased thickness of the basal laminae between LH +6, 8 and 13 in the luminal epithelium. The within-group coefficient of variation was 16% and 27% for LH +6 and LH +13 groups but only 2% for LH +8. Study 4 demonstrated an increase in basal lamina thickness associated with small blood vessels between LH +6 and LH +10 in normal fertile women. The basal lamina provides the interface between epithelial and mesenchymal environments; changes in its structure can alter the phenotypic expression of the epithelia. It is one of the maternal barriers that must be transgressed by the trophoblast during implantation. Together, these combined studies provide quantitative baseline structural information on the electron microscopical appearance of the basal lamina during the luteal phase of the menstrual cycle. Keywords:basal lamina/endometrium/human/morphometry
Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells
Authors: Hidehiko Kawano, Hajime Tsuji, Hiromi Nishimura, Shinzo Kimura, Shingo Yano, Naoki Ukimura, Yasufumi Kunieda, Masami Yoshizumi, Tatsuya Sugano, Katsumi Nakagawa, Haruchika Masuda, Shohei Sawada, Masao Nakagawa
Journal: Blood (2001)
Corticosteroid-Dependent Sodium Transport in a Novel Immortalized Mouse Collecting Duct Principal Cell Line
Authors: MARCELLE BENS, VÉRONIQUE VALLET, FRANC[COMBINING CEDILLA]OISE CLUZEAUD, LAURENT PASCUAL-LETALLEC, AXEL KAHN, MARIE E. RAFESTIN-OBLIN, BERNARD C. ROSSIER, ALAIN VANDEWALLE
Journal: Journal of the American Society of Nephrology (1999)

The final control of sodium balance takes place in the cortical collecting duct (CCD) of the nephron, where corticosteroid hormones regulate sodium reabsorption by acting through mineralocorticoid (MR) and/or glucocorticoid (GR) receptors. A clone of principal CCD cells (mpkCCDc14) has been established that is derived from a transgenic mouse (SV40 large T antigen under the control of the SV40 enhancer/L-type pyruvate kinase promoter). Cells grown on filters form polarized monolayers with high electrical transepithelial resistance (R(T) approximately 4700 ohm x cm2) and potential difference (P(D) approximately -50 mV) and have an amiloride-sensitive electrogenic sodium transport, as assessed by the short-circuit current method (Isc approximately 11 microA/cm2). Reverse transcription-PCR experiments using rat MR primers, [3H]aldosterone, and [3H]dexamethasone binding and competition studies indicated that the mpkCCDc14 cells exhibit specific MR and GR. Aldosterone increased Isc in a dose- (10(-10) to 10(-6) M) and time-dependent (2 to 72 h) manner, whereas corticosterone only transiently increased Isc (2 to 6 h). Consistent with the expression of 11beta-hydroxysteroid dehydrogenase type 2, which metabolizes glucocorticoids to inactive 11-dehydroderivates, carbenoxolone potentiated the corticosterone-stimulated Isc. Aldosterone (5x10(-7) M)-induced Isc (fourfold) was associated with a three- to fivefold increase in alpha-ENaC mRNA (but not in those for beta- or gamma-ENaC) and three- to 10-fold increases in alpha-ENaC protein synthesis. In conclusion, this new immortalized mammalian CCD clonal cell line has retained a high level of epithelial differentiation and sodium transport stimulated by aldosterone and therefore represents a useful mammalian cell system for identifying the genes controlled by aldosterone.
Doctors and State Medicine: A Study of the British Health Service
Authors: E. J. Potchen
Journal: JAMA (1967)

Dr. Forsyth, an authority on the problems of state medicine in England, concisely presents the complexities and politics surrounding the historical development and effectiveness of the British Health Service. He stresses, that the British Medical Association's leadership has not been representative of the main body of medical practitioners. "To exert weight in medical politics, one must have money, and above all, time. Representative medical bodies are, therefore, inevitably weighed in favor of age, affluence, private practice, and the suburb." He points out that "the workload of medical administrators, newly-qualified doctors, and those working in urban working-class areas does not allow them time to participate in medical politics at the local level, and it is usually only through participation at this level, that influence can be exerted nationally." By emphasizing the conflict between specialist and general practitioners in England, he demonstrates that the physicians' drive for personal gain adversely affects the
Visceral Fat Is a Major Contributor for Multiple Risk Factor Clustering in Japanese Men With Impaired Glucose Tolerance
Authors: Hiroyuki Nagaretani, Tadashi Nakamura, Tohru Funahashi, Kazuaki Kotani, Minoru Miyanaga, Katsuto Tokunaga, Masahiko Takahashi, Hitoshi Nishizawa, Ken Kishida, Hiroshi Kuriyama, Kikuko Hotta, Shizuya Yamashita, Yuji Matsuzawa
Journal: Diabetes Care (2001)

OBJECTIVE—The significance of abdominal visceral fat accumulation was evaluated in Japanese men with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS—The IGT subjects (n = 123) were aged 55 ± 9 years with a BMI of 24 ± 3 kg/m2. The 148 control subjects with normal glucose tolerance (NGT) were matched for age and BMI. IGT and NGT were classified according to the 1985 World Health Organization criteria. Abdominal fat distribution was analyzed by computed tomography at umbilical level. Plasma lipid, glucose, and insulin concentrations and blood pressure (BP) were measured. RESULTS—In subjects with IGT, the average visceral fat area (VFA) was significantly greater than in subjects with NGT. Fasting insulin, the sum of insulin concentrations during an oral glucose tolerance test, insulin resistance according to a homeostasis model assessment for insulin resistance (HOMA-IR), systolic BP, and serum triglyceride were significantly higher, whereas the ΔI30–0/ΔG30–0 was significantly lower, in subjects with IGT. Subjects with IGT and NGT were then divided into three subgroups according to the number of risk factors they possessed (dyslipidemia, hypertension, neither, or both). In both IGT and NGT subjects, BMI, VFA, subcutaneous fat area, fasting insulin, HOMA-IR, and insulin secretion of the homeostasis model assessment were significantly higher in the double–risk factor subgroup than in the no–risk factor subgroup, and VFA was a potent and independent variable in association with the presence of a double risk factor. CONCLUSIONS—Visceral fat accumulation is a major contributor for multiple risk factor clustering in Japanese men with IGT and NGT.
Does Thyroid Supplementation Accelerate Tricyclic Antidepressant Response? A Review and Meta-Analysis of the Literature
Authors: Lori L. Altshuler, Michael Bauer, Mark A. Frye, Michael J. Gitlin, Jim Mintz, Martin P. Szuba, Kristin L. Leight, Peter C. Whybrow
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The delayed onset of therapeutic response to antidepressants remains a major problem in the treatment of depression. Among the strategies to accelerate response to treatment, the early addition of thyroid hormone to antidepressants has been suggested as a viable method. The authors performed a meta-analysis of the literature on the use of thyroid hormone supplementation to accelerate the treatment of depression to determine whether there is sufficient evidence to support the clinical efficacy of this strategy. METHOD: Both a computer-aided search of the National Library of Medicine MEDLINE and an intensive search by hand were conducted to identify all double-blind, placebo-controlled studies assessing the concomitant administration of thyroid hormone and antidepressant to accelerate clinical response in patients with nonrefractory depression. RESULTS: Six studies were identified. All were conducted with triiodothyronine (T3) and a tricyclic antidepressant. Five of the six studies found T3 to be significantly more effective than placebo in accelerating clinical response. The pooled, weighted effect size index was 0.58, and the average effect was highly significant. Further, the effects of T3 acceleration were greater as the percentage of women participating in the study increased. CONCLUSIONS: This meta-analysis supports the efficacy of T3 in accelerating clinical response to tricyclic antidepressants in patients with nonrefractory depression. Furthermore, women may be more likely than men to benefit from this intervention.
Randomized Phase II Study of Adjuvant Chemotherapy with Long-term S-1 versus Cisplatin+S-1 in Completely Resected Stage II–IIIA Non–Small Cell Lung Cancer
Authors: Yasuo Iwamoto, Tetsuya Mitsudomi, Kazuko Sakai, Takeharu Yamanaka, Hiroshige Yoshioka, Makoto Takahama, Masahiro Yoshimura, Ichiro Yoshino, Masayuki Takeda, Shunichi Sugawara, Tomoya Kawaguchi, Toshiaki Takahashi, Mitsunori Ohta, Yukito Ichinose, Shinji Atagi, Morihito Okada, Hideo Saka, Kazuhiko Nakagawa, Yoichi Nakanishi, Kazuto Nishio
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The aims of this study were to evaluate the efficacy and safety of S-1 versus cisplatin (CDDP)+S-1 in patients with completely resected stage II and IIIA non–small cell lung cancer, and to identify predictive biomarkers whose expression in the tumors was significantly associated with patient outcome. Experimental Design: A total of 200 patients were randomly assigned to receive either S-1 (40 mg/m2 twice per day) for 2 consecutive weeks repeated every 3 weeks for 1 year (S group) or CDDP (60 mg/m2) on day 1 plus oral S-1 (40 mg/m2 twice per day) for 2 consecutive weeks repeated every 3 weeks for four cycles (CS group) within 8 weeks after surgery. The primary endpoints were relapse-free survival (RFS) at 2 years and identification of predictive biomarkers whose expressions have been reported to be associated with CDDP or fluoropyrimidine sensitivity. Results: The RFS rate at 2 years was 65.6% (95% confidence intervals; CI, 55.3–74.0%) in the S group and 58.1% (95% CI, 47.7–67.2%) in the CS group. The only gene with interaction of P &amp;lt; 0.05 was uridine monophosphate synthase (UMPS; P = 0.0348). The benefit that members of the S group had over members of the CS group was higher expression of UMPS. In vitro and in vivo experiments confirmed that overexpression of UMPS enhanced the antitumor effect of fluoropyrimidine. Conclusions: Adjuvant S-1 monotherapy might be preferable to CDDP+S-1 for patients with completely resected NSCLC. UMPS expression may define a patient subset that would benefit from long-term postoperative S-1 monotherapy. Clin Cancer Res; 21(23); 5245–52. ©2015 AACR.
Cellular localization of a vasoactive intestinal peptide in the mammalian and avian gastrointestinal tract
Authors: J. M. Polak, A. G. E. Pearse, J-C. Garaud, S. R. Bloom
Journal: Gut (1974)

Immunohistochemical studies using an antiserum to a pure porcine vasoactive intestinal peptide, possessing no cross reactivity against the related hormones glucagon, secretin, and gastrin-inhibitory peptide, revealed a wide distribution of vasoactive intestinal peptide cells throughout the entire length of the mammalian and avian gut. The highest numbers of cells were present in the small intestine and more particularly in the large intestine in all species investigated. Three types of endocrine cell in the mammalian gut are sufficiently widely distributed to be considered as the sites for production of vasoactive intestinal peptide. In the avian gut there are only two identifiable cell types. Sequential immunofluorescence and silver staining showed, in the bird, that the enterochromaffin (EC) cell was not responsible. This procedure could not be used in our mammalian gut samples but here serial section immunofluorescence for enteroglucagon and vasoactive intestinal peptide indicated that the two cells were not identical and that each was differently localized in the mucosa. These results leave the D cell of the Wiesbaden classification as the most likely site for the production of vasoactive intestinal peptide. The final identification must come from successful immune electron cytochemistry but this has not yet been achieved.