tbuckley/cabot-search huggingface dataset:
Working with the private sector: the need for institutional guidelines
Authors: G. Walt
Journal: BMJ (2002)

<i>Cooperation between academic institutions and the private sector does not always run smoothly. Gill Walt, Ruairi Brugha, and Andy Haines from the London School of Hygiene and Tropical Medicine point up the need for guidance on entering into partnership with a commercial partner and describe the school9s experience in formulating guidelines for its staff</i>
Discussion Required for Correct Interpretation
Authors: Radek Bukowski, Gary D. V Hankins, George R Saade, Steve Thornton
Journal: PLoS Medicine (2006)

I read the paper by Chi et al. with interest.The authors found a greater hypoxia response gene expression in carcinomas than stromal cells grown in vitro, but were not sure of the underlying explanation (see Discussion in [1]).The underlying explanation may be the difference in mitotic activity and hence metabolic activity between these two cell types, such that hypoxia may be present within cancer cells, although the surrounding culture media may have similar oxygen levels as the stromal cultures.The differences in mitotic activity could also explain greater hypoxia-related gene expression in clear-cell carcinoma compared with chromophobe carcinoma, normal tissue, or oncocytoma, as clear-cell carcinomas are more active mitotically.Did the authors compare the hypoxia gene expression with mitotic activity in various tumors?
Myelopathy After Duck Embryo Vaccine
Authors: Gordon J. Gilbert
Journal: JAMA (1973)

<h3>To the Editor.—</h3> As a neurologist, I read the article, "Myelopathy After Duck Embryo Rabies Vaccine" by Mozar et al (224:1605-1607, 1973) with concern. I could find no evidence to justify the diagnosis of "myelopathy" that the authors emphasized in their title and report. Their patient did not have Babinski signs, or any other evidence of pyramidal tract disease; she had no sensory loss to suggest spinal cord localization; there were no sphincteric disturbances. Absence of the superficial abdominal reflexes in a 56-year-old woman may well be a normal finding and certainly does not indicate "myelopathy." Their patient had generalized weakness, dysphagia, and hypoactive deep tendon reflexes. The clinical picture might raise a question of the Guillain-Barré syndrome, with sparing of sensation and sphincter function, hyporeflexia, and diffuse weakness of the extremities and trunk.
Phase III results for the novel neurokinin-1 (NK-1) receptor antagonist, casopitant: Single oral dosing regimen for chemotherapy-induced nausea and vomiting (CINV) in patients (Pts) receiving highly emetogenic chemotherapy (HEC)
Authors: J. Herrstedt, S. Grunberg, J. Rolski, R. R. Bandekar, M. E. Guckert, I. Camlett, M. W. Russo, J. Strausz, Z. Aziz, S. Thorn
Journal: Journal of Clinical Oncology (2008)

9549 Background: In a phase II dose-ranging trial, casopitant, a novel NK-1 receptor antagonist, demonstrated efficacy in preventing CINV in pts receiving HEC. This Phase III trial evaluated 2 casopitant dosing regimens, here we present results of a single oral dose of casopitant (150 mg) added to ondansetron/dexamethasone (OND/DEX) for the prevention CINV events in pts receiving HEC. Methods: This multinational, double-blind, active-controlled trial included 810 pts, with 99% receiving cisplatin-based HEC regimens for up to 6 cycles. Pts were randomized to receive no additional therapy (CTRL; OND 32 mg IV + DEX 20 mg PO), or a single dose casopitant arm (150 mg PO + OND 32 mg IV + DEX 12 mg PO) D1, plus DEX 8 mg PO BID D2–4 for all pts. An additional arm evaluated a 3-day IV/oral dose (casopitant 90 mg IV + OND 32 mg IV + DEX 12 mg PO) on D1 plus casopitant 50 mg PO D2–3 + DEX 8 mg PO QD D2–4. Complete Response (CR; no vomiting/retching, rescue medications) in the first 120 hours of HEC was the primary endpoint. Results: In the first 5 days of cycle 1, pts receiving a single oral dose of casopitant achieved a statistically significant improvement (2.5% level of significance adjusted for 2 primary comparisons) in CR rates compared with CTRL. This clinical benefit appeared to be maintained in cycles 2–6 of HEC. Significant improvements were observed in CR in the acute and delayed phases. Clinically meaningful improvements in the secondary endpoints of no significant nausea (SN), and no nausea were also observed. AEs occurred with similar frequency in all arms. Common AEs were neutropenia, leukopenia and anemia. Conclusions: A single oral dose of casopitant added to a regimen of OND/DEX provided a clinically significant reduction in the number of pts experiencing CINV events over the first 5 days after HEC. This benefit appeared to be maintained through repeat cycles. This regimen was generally well tolerated over all cycles. Cycle of HEC Endpoints (0–120 hrs) CTRL n=265 (%) 150 mg PO D1 n=266 (%) P-value 1 Complete Response 175 (66) 228 (86) <0.0001 Acute (0–24 hrs) 234 (88) 253 (95) 0.0044 Delayed (24–120 hrs) 175 (66) 228 (86) <0.0001 No vomiting 179 (68) 236 (89) <0.0001 No SN (VAS < 25 mm) 184 (69) 207 (78) 0.0272 No nausea (VAS <5 mm) 121 (46) 151 (57) 0.0105 2 Complete Response 113/146 (77) 123/131 (94) NA 3 Complete Response 92/118 (78) 89/97 (92) NA 4 Complete Response 66/89 (74) 70/75 (93) NA 5 Complete Response 13/15 (97) 10/11 (91) NA 6 Complete Response 5/9 (56) 9/9 (100) NA Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients
Authors: S K Kumar, A Dispenzieri, M Q Lacy, M A Gertz, F K Buadi, S Pandey, P Kapoor, D Dingli, S R Hayman, N Leung, J Lust, A McCurdy, S J Russell, S R Zeldenrust, R A Kyle, S V Rajkumar
Journal: Leukemia (2013)
Abstract B21: E7050, a Met kinase inhibitor, reverses three different mechanisms of hepatocyte growth factor-induced resistance to tyrosine kinase inhibitors in EGFR mutant lung cancer cells
Authors: Takayuki Nakagawa, Shinji Takeuchi, Tadaaki Yamada, Kenji Kita, Seiji Yano
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Hepatocyte growth factor (HGF) induces resistance to reversible and irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutant lung cancer cells by activating Met and downstream PI3K/Akt pathway. In addition, HGF accelerates expansion of minor clones with Met amplification and facilitates EGFR-TKI resistance. Purpose of this study is to determine whether E7050, a Met kinase inhibitor, could overcome these three resistant mechanisms to EGFR-TKIs. Experimental design: Effect of E7050 on HGF-induced resistance to reversible (gefitinib), irreversible (BIBW2992), and mutant selective (WZ4002) EGFR-TKIs was determined using EGFR-mutant human lung cancer cell lines, PC-9 and HCC827 with exon 19 deletion, and H1975 with T790M secondary mutation. As an in vivo models, PC-9 cells mixed with HGF producing fibroblasts, MRC-5, were subcutaneously inoculated into SCID mice and therapeutic effect of E7050 combined with gefitinib was examined. Results: We found that E7050 circumvented resistance to all of reversible, irreversible, and mutant selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking Met/Gab1/PI3K/Akt pathway in vitro. E7050 also prevented emergence of gefitinib resistant HCC827 cells induced by continuous exposure to HGF. In vivo model, E7050 combined with gefitinib dramatically regressed the tumor growth, associating with inhibiting Akt phosphorylation in cancer cells. Conclusions: E7050, a Met kinase inhibitor, reverses three different mechanisms of gefitinib resistance induced by HGF, suggesting usefulness of E7050 for overcoming HGF-induced resistance to gefitinib and new generation EGFR-TKIs.
U.S.-Japan joint meeting on the toxicological characterization of environmental chemicals of mutual interest.
Authors: T Damstra, Y Kurokawa
Journal: Environmental Health Perspectives (1990)

The paper describes deliberations of a meeting between scientists from the U.S. National Toxicology Program and the National Institute of Hygienic Sciences, Tokyo, Japan. The scientific approaches and experimental processes used by each organization in designing, conducting, and evaluating the short-term and long-term toxicity/carcinogenicity of environmental chemicals were evaluated.
Clostridium difficile and the microbiota
Authors: Anna M. Seekatz, Vincent B. Young
Journal: Journal of Clinical Investigation (2014)

Clostridium difficile infection (CDI) is the leading health care–associated illness. Both human and animal models have demonstrated the importance of the gut microbiota’s capability of providing colonization resistance against C. difficile. Risk factors for disease development include antibiotic use, which disrupts the gut microbiota, leading to the loss of colonization resistance and subsequent CDI. Identification of the specific microbes capable of restoring this function remains elusive. Future studies directed at how microbial communities influence the metabolic environment may help elucidate the role of the microbiota in disease development. These findings will improve current biotherapeutics for patients with CDI, particularly those with recurrent disease.
Towards characterizing what the L2 learner knows
Authors: Esther Torrego
Journal: Behavioral and Brain Sciences (1996)

Abstract This target article is mostly a presentation of experimental research devoted to the larger issue of the role of Universal Grammar in second language learning. Deliberately excluding the aspects of human cognition that makes second language (L2) so variant, Epstein et al. focus on what the learners may know and how they come to know it. This is the aspect of Epstein et al.'s work which is more limiting, and potentially more interesting.
Formation of Antibodies to Factor VIII in Patients with Hemophilia A Who Are Treated with Interferon for Chronic Hepatitis C
Authors: Eveline P. Mauser-Bunschoten
Journal: Annals of Internal Medicine (1996)

Objective: To evaluate the risk for development of antibodies to factor VIII (factor VIII inhibitors) during and after interferon therapy in patients with hemophilia A and chronic hepatitis C infection. Design: Patients were divided into two treatment groups and an untreated control group. Test results from the two treatment groups were compared with those from the control group. Setting: 3 clinical centers in the Netherlands. Patients: 35 men with hemophilia A who had acquired hepatitis C through the use of plasma-derived clotting factor concentrates. Measurements: Patients were tested for factor VIII inhibitors before the start of interferon therapy and every 6 months thereafter. Results: 21 patients with hemophilia A received interferon therapy for chronic hepatitis C infection for a mean of 19.5 months (range, 0.5 to 36 months). In 2 patients, inhibitors were detected on one occasion (maximum titer, 1.2 Bethesda units/mL) during interferon therapy. In 3 patients who were known to have had inhibitors before interferon therapy, no anamnestic reaction was seen during treatment. In 3 of 14 untreated controls who were followed for a mean of 28 months (range, 18 to 40 months), inhibitors were detected on one occasion (maximum titer, 2.3 Bethesda units/mL). Conclusion: Long-term interferon therapy in patients with hemophilia did not increase the risk for development of factor VIII inhibitors.
Bacteremic Infections Due to Clindamycin-Resistant Streptococci
Authors: Mark S. Drapkin
Journal: JAMA (1976)

We have recently observed four patients with bacteremic infections due to group A streptococci that were highly resistant to clindamycin and only moderately susceptible to erythromycin. Two of the infections developed while the patients were receiving clindamycin. The organisms were not beta-hemolytic under standard conditions nor were they M or T typable. We urge that all streptococci isolated from patients with serious infections be grouped serologically and be tested for antibiotic susceptibilities, especially if therapy with antibiotics other than penicillin is to be considered.
A FASCICLE OF CASES IN SUGGESTIVE (HYPNOTIC) THERAPEUTICS.
Authors: H. S. DRAYTON
Journal: JAMA (1898)

The American medical world has shown itself easily affected, as a rule, by the current of events, medical and surgical, in Europe. The experiments of Koch with tuberculin, of Klebs, Loeffler and Roux with antitoxin, and the various suggestions with reference to organic extracts—cerebral, testicular, thyroid, etc.—that have crossed the Atlantic have received a ready attention, in some cases developing into a wave of enthusiasm, and have found practical recognition in employment by many of our progressive medical brethren. I would refer merely to the disappointment that some have experienced in applying these more or less authoritative procedures, and remark<i>en passant</i>, that the wisest of us are subject to mistake occasionally through the very earnestness of our desire to wrest from old Mors one at least of his dreaded instrumentalities for human decimation. In view of the readiness of the American profession to entertain foreign advice in
AN ANALYSIS OF FIFTEEN HUNDRED CASES OF TUBERCULOSISDISCHARGED FROM THE ADIRONDACK COTTAGE SANITARIUM FROM TWO TO EIGHTEEN TEARS AGO.
Authors: LAWRASON BROWN
Journal: JAMA (1903)

In a disease of so relapsing a nature as tuberculosis the inexorable test of time is rarely applied in the study of the results obtained by any form of treatment. The object of this research has been to apply this crucial test to the permanency of the beneficial effects which are undoubtedly obtained by the sanatorium treatment of pulmonary tuberculosis. The results of treatment in this disease vary directly with so many factors that it is exceedingly difficult to compare the results obtained by different observers. The use of different classifications, and in some instances the different interpretation of the same classification render any comparison a difficult task. Take, for example, the terms "apparently cured" and "cured." One observer applies them to patients who have gone a few months without symptoms and whose physical signs, if at all abnormal, are indicative of a healed lesion. Another thinks the
Combined effect of dextrose and sodium chloride on red cell osmotic fragility
Authors: Sang K. Minn, Kwanruen Harnchonboth, Emanuel E. Mandel
Journal: American Journal of Hematology (1978)

Abstract Observations indicating an enhancing effect of sodium on hemolysis of red cells suspended in dextrose solution prompted study of the mechanism of this effect. Osmotic fragility of red cells from normal subjects and from patients was measured in 5% dextrose solution (5D/W), 5% dextrose combined with various concentrations of sodium chloride (5D/NaCl), lithium chloride, and potassium chloride. The influence of ouabain on osmotic hemolysis in 5D/ NaCl was also studied, and the glucose content of ghost red cells was determined when incubated in 5% dextrose with 0.05% NaCl (5D/O.05NaCl), as compared with 5D/W. In the presence of minimal amounts of NaCl (0.05%) at pH 4.8, average hemolysis was greater than in the absence of NaCl, ie, 39% vs 24% in normal subjects (P &lt; 0.02) and 40% vs 31% in a group of unselected patients (P &lt; 0.05). When the pH was adjusted to 7.4 in the patient group, the results were 34% vs 21% (P &lt; 0.05). The sodium‐induced enhancement of hemolysis in dextrose solution was virtually duplicated when LiCl and KCl were substituted for NaCl (P &lt; 0.01 and &lt; 0.05, respectively). On the other hand, in the presence of ouabain, the sodium‐induced enhancement of hemolysis was abolished. The overall glucose content of ghost red cells incubated in 5D/0.05NaCl was 53% greater than in 5D/W (P &lt; 0.005), whereas with ghost red cells depleted of adenosine triphosphate (ATP), it was only 32% greater (P &lt; 0.01). These results suggest that glucose transport across the red cell membrane is enhanced by the sodium ion, presumably by triggering the membrane sodium‐potassium ATPase system.
General Medical Care and the Education of Internists in University Hospitals
Authors: JACQUELINE KOSECOFF
Journal: Annals of Internal Medicine (1985)

Fifteen general internal medicine group practices in university teaching hospitals were studied to evaluate their primary care services and education. Data were collected over 9 months from physicians, patients, and medical records, and by observation. All institutions had closed their general medical clinics. Many patients being treated in group practices were very sick; 57% had hypertension; 21% were diabetic; and 45% could not work. Most were satisfied with their care. Care for acute problems from a health care provider in the practice was available quickly; regular physicians were harder to see. House staff and faculty spent little time in the practices. Few practices used teams; most used traditional attending and house staff models. Practice physicians could not easily determine when patients were seen in the institution's emergency department or were hospitalized. Quality of care standards were not uniformly met. Finally, the structure of academic centers appeared to inhibit the practices' performance, suggesting a need for further appraisal of relationships between university hospitals and their ambulatory care units.
Concern Over Prozac-Induced Tumor Growth May Dwindle Following FDA Study
Authors: J. Mathews
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Concern Over Prozac-Induced Tumor Growth May Dwindle Following FDA Study Get access James Mathews James Mathews Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 17, 6 September 1995, Pages 1285–1286, https://doi.org/10.1093/jnci/87.17.1285 Published: 06 September 1995
Abstract 5100: MMP-2 suppression inhibits α5β1 integrin and IL-3-mediated Stat5 activation and proliferation of endothelial cells.
Authors: Dilip Rajasekhar Maddirela, Divya Kesanakurti, Chandramu Chetty, Jasti S. Rao
Journal: Cancer Research (2013)

Abstract Endothelial cell (EC) proliferation is a major component of angiogenesis in glioblastoma multiforme (GBM) and is regulated by several growth factors including IL-3. In this study, we have evaluated the effect of conditioned media (CM) obtained from MMP-2 knockdown xenograft 4910 and 5310 cell lines by pMMP-2 siRNA (pM.si) on the growth of ECs. Western blot analysis of CM from pM.si-treated 4910 and 5310 cells showed a significant downregulation of MMP-2 and IL-3 expression compared to mock- and pSV (scrambled vector)-CM. Proliferation decreased in ECs cultured on pM.si-CM from the xenograft cells when compared to ECs cultured on mock- or pSV-CM as determined by Ki-67 staining and MTT assays. Since Stat5 is a known target of IL-3, induces EC proliferation, and promotes neo-angiogenesis, we examined the role of pM.si in regulating IL-3-mediated Jak2/Stat5 signaling in ECs. Jak2/Stat5 suppression in ECs when cultured on pM.si-CM resulted in the decreased expression of integrin β1, Stat5, Bcl2 and Cyclin D2 at the transcription level as compared with ECs cultured on mock- and pSV-CM, as confirmed by RT-PCR analysis. Supplementation of recombinant human IL-3 counteracted and noticeably reversed pM.si-inhibited IL-3Rα, Jak2, p-Stat5 expression and proliferation of ECs, thereby confirming the role of MMP-2 in the regulation of α5β1/IL-3 mediated Jak2/Stat5 signaling. Immunoprecipitation and immunofluorescence studies revealed MMP-2 knockdown resulted in the decreased interaction of MMP-2 and integrin α5β1 in ECs, thereby implicating the downregulation of Jak2/Stat5 expression. Immunohistochemical analysis in tumor sections corroborated our in vitro studies, suggesting that the expression of p-Stat5 and Bcl2 are significantly decreased upon pM.si treatment compared to mock or pSV treatments. Our results suggest that MMP-2 knockdown by pM.si can lead to a significant inhibition of IL-3-induced proliferation of ECs and can be an effective anti-angiogenic therapy when treating patients with GBM in the future. Citation Format: Dilip Rajasekhar Maddirela, Divya Kesanakurti, Chandramu Chetty, Jasti S. Rao. MMP-2 suppression inhibits α5β1 integrin and IL-3-mediated Stat5 activation and proliferation of endothelial cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5100. doi:10.1158/1538-7445.AM2013-5100
Management of women with smears showing mild dyskaryosis
Authors: R Hammond
Journal: BMJ (1994)

Higher survival rates have been associated with referral to specialist centres for a wide range of childhood cancers.4The evidence relating to tumours occurring in adolescents but hardly ever in children is much sparser, though men with testicular teratoma may benefit from initial referral to a specialist centre.56Continuing specialist follow up is essential.Late effects occur, though they are rarely fatal and should be seen in the context of improved survival.They can affect virtually any system and mostly result from treatment rather than the cancer.7 Survivors need to be kept under surveillance and, when appropriate, given information on the risk of comolications, especially impaired fertility, second cancers, and cardiovascular damage.Nevertheless, it should be emphasised that survivors are in general fit, employable, and in most respects indistinguishable from their peers.The news about cancer in adolescents is therefore mainly good and should get better as a result of two recent initiatives.This month saw the first international conference on cancer and the adolescent, organised by the Yorkshire Regional Cancer Organisation.It coincided with the launch of an appeal by the Teenage Cancer Trust aimed at improving facilities for adolescents with cancer.Together these initiatives should stimulate greater interest in a group whose welfare may have been neglected previously.
Web Resources for Model Organism Studies
Authors: Bixia Tang, Yanqing Wang, Junwei Zhu, Wenming Zhao
Journal: Genomics Proteomics & Bioinformatics (2015)

Abstract An ever-growing number of resources on model organisms have emerged with the continued development of sequencing technologies. In this paper, we review 13 databases of model organisms, most of which are reported by the National Institutes of Health of the United States (NIH; http://www.nih.gov/science/models/). We provide a brief description for each database, as well as detail its data source and types, functions, tools, and availability of access. In addition, we also provide a quality assessment about these databases. Significantly, the organism databases instituted in the early 1990s—such as the Mouse Genome Database (MGD), Saccharomyces Genome Database (SGD), and FlyBase—have developed into what are now comprehensive, core authority resources. Furthermore, all of the databases mentioned here update continually according to user feedback and with advancing technologies.
Richter's hernia at site of insertion of laparoscope.
Authors: D Stewart
Journal: BMJ (1977)

susceptible to obstruction as a result of lymnphoid hyperplasia until involution of this lymphoid tissue occurs.This relationship would account for the characteristic age distribution of acute appendicitis.On this basis lymphoid hyperplasia occurring during viral exanthemata and bacterial infections could lead to appendicitis.However, one study has shown that there is no greater incidence of acute appendicitis in children with these infections than there is in children who are otherwise well."An alternative explanation is that obstruction is due to muscular spasm in the appendix associated with a low-fibre diet, as is thought to occur in the colon, and this would account for the geographical distribution of the disease.