tbuckley/cabot-search huggingface dataset:
Abstract 2568: Application of novel phospholipid conjugated Toll like receptor 7 ligands for cancer therapy by topical and systemic administration
Authors: Dennis A. Carson, Tomoko Hayashi, Brian Crain, Shiyin Yao, Jeffrey Cheng, Nadia Passini, Roberto Maj, Emanuela Mura, Howard Cottam, Johanna Holldack, Alcide Barberis
Journal: Cancer Research (2014)

Abstract Introduction: Toll like receptor 7 (TLR7) activators are effective cancer immunotherapeutic drugs. However, the only clinically approved TLR7 ligand, imiquimod (IMQ), is absorbed into the systemic circulation inducing off-target adverse effects. To overcome this problem, we synthesized phospholipid-conjugated TLR7-specific activators. The objective of this project was to evaluate the safety and the anti-cancer activities of two TLR7 ligand-phospholipid conjugates, designated TMX-201 and TMX-202. Procedures: In vitro immune activities of TLR7 agonists were compared in human and mouse leukocytes. Anti-malignant effects were evaluated using Inv-MycERTAM transgenic model of pre-malignant keratinocyte proliferation and murine models of 4T1 breast cancer and B16 melanoma. Results: TMX-201 and TMX-202 were more potent cytokine inducers than IMQ in both mouse and human mononuclear cells. TMX-201 and TMX-202 showed less off-target binding compared to IMQ. The maximum tolerated doses of IMQ, TMX-201, and TMX-202 by i.v. administration were 15, 75 and 150 mg/kg, respectively. Topical administration of TMX-202 gel significantly reduced acanthosis in the Inv-mycERTAM model without inducing systemic cytokine production. Systemic administration of TMX-201 (4mg/kg) suppressed the growth of established subcutaneous B16 melanoma by 46%, without discernible adverse effects. Systemic or intra-tumor administration of TMX-201, in combination with anti-CTLA4 antibody, significantly suppressed lung metastasis formation in the 4T1 breast cancer model. Conclusion: TMX-201 and TMX-202 displayed more potent immune stimulatory activity than IMQ with fewer off-target effects. These phospholipid-conjugated TLR7 agonists showed anti-cancer efficacy in three different mouse models. The new compounds may be useful topical and systemic therapeutic agents for cancer therapy, alone or in combination with checkpoint inhibitors. Table 1.TMX-201 effect on lung metastases in the 4T1 breast cancer modelTreatmentMetastatic nodulesVehicle + isotype control33.5 ± 5.2TMX-20123.6 ± 4.9Anti-CTLA432.4 ± 13.6TMX-201 i.p. + anti-CTLA416 ± 2.7*TMX-201 i.t. + anti-CTLA413 ± 2.6**p&amp;lt;0.05 vs vehicle+isotype control group Citation Format: Dennis A. Carson, Tomoko Hayashi, Brian Crain, Shiyin Yao, Jeffrey Cheng, Nadia Passini, Roberto Maj, Emanuela Mura, Howard Cottam, Johanna Holldack, Alcide Barberis. Application of novel phospholipid conjugated Toll like receptor 7 ligands for cancer therapy by topical and systemic administration. [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 2568. doi:10.1158/1538-7445.AM2014-2568
Allergic contact dermatitis to two antioxidants in latex gloves: 4,4′-thiobis(6-tert-butyl-meta-cresol) (Lowinox 44S36) and butylhydroxyanisole
Authors: Phoebe Rich, Mary Lou Belozer, Patti Norris, Frances J. Storrs
Journal: Journal of the American Academy of Dermatology (1991)
Rubella in England, Scotland and Wales
Authors: P Tookey
Journal: Eurosurveillance (2004)

Rubella vaccine was offered to schoolgirls in the United Kingdom (UK) from 1970, with antenatal testing and postpartum vaccination for susceptible women introduced during the 1970s. Mass vaccination with MMR of children aged 12-15 months was introduced in 1988; schoolgirl vaccination was discontinued in 1996 and replaced by a second dose of MMR for pre-school children; postpartum vaccination of susceptible women identified through antenatal testing continues. Rubella was made a notifiable disease in 1988, and is monitored through clinical and laboratory reports; data are available on rubella associated terminations and congenital rubella syndrome(CRS) births, rubella susceptibility in population subgroups, and vaccine uptake. Reported cases of CRS declined from about 50 a year 1971-75 to just over 20 a year 1986-90, and rubella associated terminations from an average of 750 to 50 a year. About 40 infants with CRS have been reported since 1991; about a third of their mothers were infected abroad, most in their country of origin (imported infections), a third were born abroad but acquired infection in the UK, and a third were UK-born. Women living in the UK who were born abroad have much higher rubella susceptibility rates than UK-born women. Although there is currently very little rubella infection circulating, uptake of MMR has dropped by over 10% since 1995. If rubella starts to circulate again, immigrant women will be at increased risk of acquiring infection in pregnancy.
α-Glucosidase Inhibition by Miglitol in NIDDM Patients
Authors: Paulus J Kingma, Paulus PCA Menheere, Jean P Sels, Arie C Nieuwenhuijzen Kruseman
Journal: Diabetes Care (1992)

Objective To determine the efficacy of the α-glucosidase inhibitor miglitol (BAYm 1099) regarding the starch content of food. Research Design and Methods Thirty-six non-insulin-dependent diabetes mellitus (NIDDM) subjects were studied in a double-blind randomized study comparing treatment with a single dosage of 100 mg miglitol or placebo and a single-blind crossover comparison of three test meals in which the carbohydrate contained either 30, 50, or 70% starch, and quantities of fat and protein were kept constant. Results Postprandial blood glucose excursions were reduced by ∼ 50% with miglitol after all test meals. In contrast, after miglitol treatment, maximum postprandial serum C-peptide and insulin values reached the same levels as after placebo treatment, although the time to reach these maximum levels was delayed. Free fatty acid values decreased after both miglitol and placebo similarly. Twenty-eight untoward events in 15 patients were reported in the miglitol treatment group and 11 events in 7 patients in the placebo treatment group. Conclusions Miglitol reduces postprandial blood glucose excursions independent of the starch content of the meal. Because no effects were found on incremental postprandial maximal levels of serum insulin and C-peptide, it may be that miglitol exerts, in addition to a delay of intestinal carbohydrate absorption, extraintestinal effects as well, particularly effects on disposition of glucose or anti-insulin counterregulatory factors.
Wildtype Kras2 can inhibit lung carcinogenesis in mice
Authors: Zhongqiu Zhang, Yian Wang, Haris G. Vikis, Leisa Johnson, Gongjie Liu, Jie Li, Marshall W. Anderson, Robert C. Sills, H.L. Hong, Theodora R. Devereux, Tyler Jacks, Kun-Liang Guan, Ming You
Journal: Nature Genetics (2001)
Testing Medications in Children
Authors: Jerry H Gurwitz
Journal: New England Journal of Medicine (2003)

pertensive effects of ACE inhibitors and angiotensin-receptor blockers may differ from the doseresponse relation for the antiproteinuric effects.In addition, he cites studies suggesting that the antiproteinuric effect of ACE inhibitors and angiotensin-receptor blockers may be additive.Although this is an exciting area of current research, larger will be needed to determine the optimal level of urinary protein excretion and the optimal doses of ACE inhibitors, angiotensin-receptor blockers, and combinations of these two classes of agents to slow the progression of nondiabetic kidney disease.
Abstract 557: Noninvasive analysis of acquired resistance to EGFR-TKI
Authors: Hideharu Kimura, Makoto Nishio, Tsutomu Daito, Kazuto Nishio
Journal: Cancer Research (2014)

Abstract BACKGROUND Epidermal growth factor receptor (EGFR) T790M mutation is associated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) resistance in non-small cell lung cancer (NSCLC). However, the tissue availability limits the genotyping of EGFR T790M mutation in the clinical setting. The aims of this study are to develop a blood-based, non-invasive approach to detect the EGFRT790M mutation in advanced NSCLC patients. Additionally, plasma concentrations of HGF, MET and amphiregulin which are also resistant factors of EGFR-TKIs EXPERIMENTAL DESIGN Plasma sample were collected from NSCLC patients with activating EGFR mutations, who had resistant to EGFR-TKIs treatment. EGFR T790M mutations were detected using droplet-digital PCR (ddPCR) system from plasma DNA at resistance to EGFR-TKI. Plasma concentrations of HGF, soluble MET (sMET) and amphiregulin were determined using enzyme-linked immunosorbent assay. The relationships between the EGFR T790M mutation status and the plasma concentrations, progression-free survival (PFS) overall survival (OS) were analyzed. RESULTS Twenty-one (35%) of the patients had EGFR T790M mutation in plasma DNA using ddPCR system. The levels amphiregulin tended to be increased at the resistance in the patients with EGFR T790M mutation. The PFS and OS of the patients with EGFR T790M mutation was significantly shorter than that of the patients without EGFR T790M mutation (P =0.03 and 0.04). The PFS of the patients who had high amphiregulin at the resistance and the OS of the patients who had high amphiregulin at pre-treatment were shorter than these of t low amphiregulin (P = 0.05 and 0.05) CONCLUSIONS The ddPCR system is a detectable method for determining the plasma EGFR T790M mutation status. The combination of EGFR T790M mutation status by ddPCR and the amphiregulin levels may aid in monitoring drug resistance and in predicting a prognosis. Citation Format: Hideharu Kimura, Makoto Nishio, Tsutomu Daito, Kazuto Nishio. Noninvasive analysis of acquired resistance to EGFR-TKI. [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 557. doi:10.1158/1538-7445.AM2014-557
Variation Reduction to Reduce Readmission
Authors: Sharon M. Weber, Gregory D. Kennedy
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Regular review: Uses of botulinum toxin injection in medicine today
Authors: A Munchau
Journal: BMJ (2000)

Botulinum neurotoxin is produced by the anaerobic bacterium Clostridium botulinum . It is the most poisonous biological substance known. Very small amounts of botulinum toxin can lead to botulism, a descending paralysis with prominent bulbar symptoms and often affecting the autonomic nervous system. Botulism can occur in two ways. It can result from infection with bacterial spores that produce and release the toxin in the body—as in enteric infectious botulism, when the bacteria grow in the intestine, and in wound botulism, when the wound becomes infected. Alternatively, botulism occurs after ingestion of the toxin (food borne botulism).1

Botulism has been recognised since the early 19th century, and there was speculation about what caused the condition. In 1822 it was suggested that a “fatty acid” in sausages was the culprit,2 and this led to the term botulism ( botulus being the Latin word for sausage). In 1897, Van Ermengen related botulism to a bacterial toxin.3

The discovery that botulinum toxin blocks neuromuscular transmission4 and thereby causes weakness laid the foundation for its development as a therapeutic tool. In 1981, the ophthalmologist Alan Scott pioneered treatment with botulinum toxin when he used it to treat strabismus.5 He paved the way for clinical research in many specialties.

#### Summary points

Botulinum toxin inhibits release of acetylcholine at the neuromuscular junction and in cholinergic sympathetic and parasympathetic neurones

Local injections of toxin weaken overactive muscles and control hypersecretion of glands supplied by cholinergic neurones

Botulinum toxin injections have an established role in some disorders of ocular motility

Botulinum toxin is the treatment of choice for focal dystonias such as torticollis and writer's cramp and for hemifacial spasm and may complement the management of spasticity

Local injections have also been shown to be beneficial in many other conditions including achalasia, chronic anal fissure, and …
In vitro and in vivo activities of novel HDAC inhibitors
Authors: Young-Lan Hyun, Cheol Soon Lee, Sun Kyung Kang, Hyun Sil Seo, Eunha Choi, Yu-Mi Song, Dongkyu Shin, Cheol Min Kim, Ho-Jin Chang, Cheol Hae Lee, Won Jang Jeong, Hee Jung Jung, Jae Hak Kim, Joong Myung Cho, Seonggu Ro
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2619 

Histone acetylation and deacetylation play essential roles in modifying chromatin structure and regulating gene expression in eukaryotes. Histone deacetylase (HDACs) regulate histone acetylation by catalyzing the removal of acetyl groups on the side chain of lysine of core nucleosomal histones. This posttranslational modification of core histone is involved in the regulation of the transcriptional activity of certain genes. It has been known that aberrant recruitment of HDAC activity is associated with the development of certain human cancers.    In this study, we have discovered series of HDAC inhibitors by using the structure-based drug discovery technologies. Among them, CG200710 and CG200720 showed promising anti-tumor profiles. They inhibit histone deacetylase activity in low range nM of IC50 against class 1 and class II HDACs. The CG200710 and CG200720 exhibited a broad spectrum of anti-proliferative activity against various cancer cell lines. However, they are not cytotoxic in the normal cells. Mechanistically, the two compounds induced concentration-dependent increase in the accumulation of acetylated histone H4 in tumor cell lines and morphological changes in HeLa cell. In addition, they showed dose dependencies in apoptosis with accumulation of cells in sub G1 phase in the FACS analysis. These effects exhibited selectively in cancer cells and were not appeared in the normal cells such as MRC5. When we administered CG200710 and CG200720 xenograft nude mice bearing human colon cancer, significant dose-dependent growth delays with no obvious signs of toxicity were observed.    In conclusion, CG200710 and CG200720, novel HDAC inhibitors that are discovered through the structure based drug discovery, show potent anti-tumor activity in cell-based assays and animal studies. Currently, preclinical studies of these compounds including various efficacy and safety studies are carrying out.
Just sign this
Authors: Trisha Greenhalgh
Journal: BMJ (2001)

Every pile of paperwork contains one, but this particular request took the biscuit. A patient had sent in the usual scribbled note accompanied by a picture of her strapping youth and a blank passport application, asking me to “endorse the attached for identification reasons.” She would call by to pick it up that night.

I had never met the youth or his mother, who had been on the list for 18 months, nor …
86. Mutation Frequency of the p53 cDNA Introduced by the Retroviral Vector
Authors: Su Su, Atushi Watanabe, Takashi Shimada
Journal: Molecular Therapy (2004)

The safety and utility of the retroviral vectors must be carefully re-evaluated for further development of gene therapy. It has been well documented that retrovirus mutates at high frequency probably because of the low fidelity of reverse transcriptase. We have previously shown that more than 10 % of clones transduced with a retroviral vector carrying the HSV-TK gene have mutations in the integrated proviral genome. The base substitution rate was estimated to be approximately 1 × 10−4 per base pair. The high mutation rate of retroviral vectors may be a potential problem in certain types of gene therapy protocols. In this study, we examined the mutation rate of the retroviral vector carrying the normal p53 cDNA, which is widely used for gene therapy of cancer. We generated the retroviral vector containing the neoR selectable marker gene and the functional p53 cDNA in the sense orientation (pG1-p53S). As controls, the retroviral vectors containing the p53 cDNA in the antisense orientation (pG1-p53AS) and the mutant p53 cDNA which has a stop codon immediately after downstream of the initiation codon (pG1-mp53S) were also constructed. The vectors were introduced into the p53 deficient lung cancer cell line, H358. G418 resistant clones were isolated and the p53 sequence in the integrated retroviral vector was analyzed by PCR-SSCP followed by direct sequencing. The transduction efficiency of pG1-p53S was significantly less than that of pG1-p53AS or pG1-mp53S. Molecular analysis of clones transduced with pG1-p53S showed that 90% of clones (93/105) have mutated p53 sequences. In contrast, the p53 mutations were identified in 1/123 clones transduced with pG1-p53AS and 1/95 clones transduced with PG1-mp53S. These results indicate that the mutation rate is strongly influenced by the sequence of inserted genes. The p53 sequence is relatively stable compared to the HSV-TK sequence. However, there is still a significant chance that cancer cells could escape from p53 gene therapy because of retroviral replication errors.
Original article: Nasal nitric oxide: longitudinal reproducibility and the effects of a nasal allergen challenge in patients with allergic rhinitis
Authors: J. D. Boot, M. L. De Kam, M. A. Mascelli, B. Miller, R. Gerth Van Wijk, H. De Groot, A. F. Cohen, Z. Diamant
Journal: Allergy (2007)

Background: Exhaled nitric oxide (eNO) is a validated noninvasive marker of airway inflammation in asthma. In patients with allergic rhinitis (AR), increased levels of nasal nitric oxide (nNO) have also been measured. However, the applicability of nNO as a marker of upper airway inflammation awaits validation. Aim: To test the longitudinal reproducibility of standardized nNO measurements in patients with AR and the effects of nasal allergen challenge. Methods: Twenty patients with clinically stable, untreated AR participated in a combined study design. First, reproducibility of nNO was tested over 1, 7, and 14–21 days. Subsequently, the effect of nasal allergen challenge on nNO was studied in a placebo‐controlled, parallel design. Nasal NO was measured with a chemoluminescence analyzer. Ten subjects randomly underwent a standardized nasal allergen challenge; 10 subjects received placebo. Response to nasal challenge was monitored by composite symptom scores. Results: There was a good reproducibility of nNO up to 7 days [coefficient of variation (CV) over 1 (16.45%) and 7 days (21.5%)], decreasing over time [CV (14–21 days): 38.3%]. As compared with placebo, allergen challenge caused a significant increase in symptom scores ( P &lt; 0.001), accompanied by a decrease in nNO at 20 min postchallenge ( P = 0.001). Furthermore, there was a gradual increase in nNO at 7 h, reaching significance at 24‐h postallergen ( P = 0.04). Conclusions: Similar to eNO in asthma, nNO is a noninvasive marker, potentially suitable to monitor upper airway inflammation following allergen‐induced late response. Present data show a good reproducibility of nNO measurements, decreasing over time, probably because of subclinical seasonal influences.
British Columbia tries to reduce stress on health services with 24 hour nurse helpline
Authors: David Spurgeon
Journal: BMJ (2001)

In an initiative echoing the UK government's attempts to reduce pressure on the NHS, the provincial government of British Columbia has launched a series of measures, including a 24 hour nurse telephone hotline, to relieve stress on overcrowded emergency rooms, overworked nurses, and busy general practitioners.

It is also distributing 1.5 million free copies of a health guidebook to its citizens and setting up an internet website. From April 2001, British Columbians will have 24 hour, freephone access to HealthGuide Nurseline, staffed by specially trained registered nurses—rather like NHS Direct. The nurses will help callers to recognise and describe health problems accurately and explain the range of medically sound treatment …
Long-term derangement of antigen presenting cells in the respiratory tract of mice following influenza virus infection
Authors: Philip Stumbles, Christophe von Garnier, Vanessa Fear, Mathew Wikstrom, Cassandra Berry, Deborah Strickland, Patrick Holt
Journal: European Respiratory Journal (2013)

Inhaled agents pose a major challenge to immunological homeostasis in the respiratory tract (RT), requiring constant screening for their risk to the host. This requires a balanced network of antigen presenting cells (APC) that can initiate tolerance or immunity as required. Respiratory viruses such as Influenza pose a serious threat of disruption of this balance via their potent inflammatory and cytotoxic activities, potentially increasing the risk of allergy or secondary infections. In this study, we used a mouse model of A/PR8/34 H1N1 Influenza Type A Virus (IAV) infection to examine its long-term effects on APC in airway mucosal (AM) and parenchymal lung (PL) tissue following IAV infection. In adult mice, we found marked differences in the kinetics of dendritic cell (DC) subsets in the AM and PL environments, with a generally more acute responses in AMDC that resolved by day 7 after infection, but with persistent depletion of CD11blo PLDC for up to 3 weeks following infection. Similarly, transient upregulation of CD40 and CD80 was observed on AMDC at day 7, but this was delayed until day 14 in PLDC. A marked depletion in tissue-resident PL macrophages was observed at day 14 post-infection, with these cells showing a persistent activation state. In mice infected at 3 weeks of age or younger, DC and macrophages showed persistent changes for up to 5 weeks following infection. These data demonstrate that IAV has differential effects on APC populations in compartments of the RT, leading to long-term derangement in the numbers and activation states of these cells, that may persistently disrupt the regulation of immunological homeostasis at this site.
Performans Statusu 2 Olan ve İleri Evre Küçük Hücreli Dışı Akciğer Kanseri Olgularında Kombinasyona Karşı Tek Ajan Kemoterapisi İki Büyük Randomize Klinik Çalışma Çerçevesinde Prognostik Faktörler ve Tedavi Seçimi
Authors: Rogerio Lilenbaum, Victoria M. Villaflor, Corey Langer, ‡ Kenneth O'Byrne, § Mary O'Brien, Helen J. Ross, Mark Socinski, Fred B. Oldham, Larissa Sandilac, Jack W. Singer, Philip Bonomi
Journal: Journal of Thoracic Oncology (2009)