tbuckley/cabot-search huggingface dataset:
Multiple Dens Evaginatus of Premolars and Molars in Chinese Dentition: A Case Report and Literature Review
Authors: Yan‐gang Rao, Li‐yang Guo, Tao Hu
Journal: International Journal of Oral Science (2010)

Dens evaginatus (DE) is a dental anomaly that occurs as an accessory tubercle on the occlusal or lingual surface of a tooth. The authors provide a literature review and report a rare case in which DE occurs on multiple mandibular premolars and maxillary molars. The patient is a 26‐year‐old Chinese woman, with a chief complaint of gingival bleeding. DE affecting teeth 17, 27, 35, and 45 was found during clinical examination. For treatment of the patient, we reduced the opposing occluding teeth, while undertaking progressive grinding of the tubercles for six months. We followed‐up for a year. This suggests the importance of examining for multiple DE during clinical practice.
937. siRNA Inhibition of MMP9 Expression Inhibits TGFβ1-Induced Calcification of Aortic Valve Interstitial Cells
Authors: Jocelyn N. Clark, Elizabeth Palmatory, Robin Brittin, Navneet R. Narula, Joe Gorman, Robert C. Gorman, Robert J. Levy
Journal: Molecular Therapy (2004)

The leading cause of both native and bioprosthetic heart valve failure is calcification, which has been linked to the expression of bone-related proteins and matrix metalloproteinases (MMP), and in particular MMP9. Previous findings in our laboratory have shown that TGFβ1 mediates calcification through an apoptotic mechanism. Furthermore, we have discovered TGFβ1 induces MMP9 expression in a time-dependent fashion in cell culture. In addition, strong positive MMP9 immunohistochemical staining in calcified aortic valves compared to minimal staining in noncalcified, bicuspid and tricuspid regurgitant valves further demonstrated MMP9 involvement in the calcification process. However, its defined role in the pathway still remains unclear. Our hypothesis is that MMP9 regulates TGFβ1 activation, ultimately influencing the calcification process in aortic valve interstitial cells. We designed small interfering RNA, siRNAs, for MMP9, targeted at both the catalytic and fibronectin sites. Zymography showed that siRNA was effective in downregulation of TGFβ1-induced MMP9 expression. The reduction of MMP9 resulted in decreased apoptosis, associated with initiation of calcification, based on negligible annexin V staining in DAPI-localized cells compared to control. Therefore, these results indicate that MMP9 may be involved in the calcification progression by influencing the activation and mechanism(s) exerted by TGFβ1.
Expression of antimicrobial peptides in cutaneous infections after skin surgery
Authors: M.R. Kesting, M. Stoeckelhuber, F. Hölzle, T. Mücke, K. Neumann, K. Woermann, F. Jacobsen, L. Steinstraesser, K.-D. Wolff, D.J. Loeffelbein, N.H. Rohleder
Journal: British Journal of Dermatology (2010)

Increasing numbers of antibiotics have lost efficiency because of bacterial resistance. The consequences can be severe when surgical wounds become infected during postoperative care. Natural peptide antibiotics, the so-called host defence peptides (HDPs), have been investigated since the 1990s in a search for alternative treatment strategies. HDPs build up a protection shield against pathological microorganisms, especially in human epithelium. The use of HDPs is currently being discussed as a new antimicrobial therapeutic strategy. Accordingly, a profound knowledge of the quantitative relationships of the effectors is essential.To evaluate differences in HDP expression between postoperatively inflamed and healthy epithelium.Expression profiles of the genes encoding HDP human beta-defensin (hBD)-1 (DEFB1, previously known as HBD-1), hBD-2 (DEFB4A, previously known as HBD-2), hBD-3 (DEFB103A, previously known as HBD-3) and psoriasin (S100A7) were assessed in samples of surgical wound healing disorders (n = 27) and healthy epithelium (n = 16) by using real-time polymerase chain reaction. Immunohistochemical staining was performed in the same samples.A significant overexpression of DEFB4A (P < 0.001), DEFB103A (P = 0.001) and S100A7 (P < 0.001) was found in cutaneous surgical site infections. Immunohistochemistry revealed intensely elevated protein levels of psoriasin in infected wounds, and differences in distribution with respect to the epithelial layers.The study demonstrates upregulated mRNA expression and protein levels of HDPs in postoperatively inflamed epithelium. The results may be a starting point for novel pharmacological treatments.
GP who was subject of a complaint found dead
Authors: R. Dobson
Journal: BMJ (2001)

Survival rates for patients with cancer continued to improve substantially throughout the 1990s despite expectations that they would level off, according to a Dutch study analysing cancer registration data since the 1950s.

The Comprehensive Cancer Centre South, in Eindhoven, has data on 200000 patients with cancer dating back 45 years covering the south east of the Netherlands. The data show a strong trend of increasing survival rates at five years compared with both the 1960s and the 1980s.

Patients aged 15–44 years had a 73% chance of surviving five …
An important lesson: TB or not TB
Authors: A. Sheikh
Journal: BMJ (1999)

I arranged for the admission of my younger sister with a deep sense of apprehension. The kind medical registrar I spoke to did his best to allay my anxieties, but he too agreed that urgent admission and assessment were warranted. Over the past two to three months she had developed symptoms of weight loss, recurrent fevers and night sweats, together with bilateral cervical lymphadenopathy. Examination on admission also showed the presence of splenomegaly. A series of investigations was promptly initiated.

When my parents asked what was wrong, I said that …
Outcomes of 11 pregnancies in three patients with recessive forms of epidermolysis bullosa
Authors: S.D. Choi, Y.C. Kho, L.M. Rhodes, G.K. Davis, M.G. Chapman, D.F. Murrell
Journal: British Journal of Dermatology (2011)

Madam, Pregnancy in the most severe recessive forms of epidermolysis bullosa (EB), such as junctional and recessive dystrophic EB, is rare with only six previously reported cases.1–6 We report three further cases, who collectively had 11 pregnancies, from our Australasian EB registry, all of whom had successful outcomes with normal vaginal delivery (NVD) and little flare of their EB. Case 1 (EB‐14) was a 36‐year‐old woman with non‐Herlitz junctional EB who was erroneously advised during her first pregnancy that her EB would flare due to pregnancy and to have a termination of pregnancy. With her subsequent pregnancy at age 26, she sought a second opinion. Immunofluorescence mapping in her case showed reduced staining with antibodies to laminin 5, β3 and γ2. Mutation studies identified two heterozygous LAMB3 mutations, R635X/1588delAG.7 We advised her that both the pregnancy and her baby should not be affected. During this pregnancy, she had pregnancy‐related urticaria; however, her blisters did not flare. She used gentian violet paint diluted onto her skin after a shower, air‐dried, with no dressings, and continued this during the pregnancy (Fig. 1). She had a NVD with induction at 39 weeks because of placental insufficiency and intrauterine growth restriction of the fetus, but had a live normal male baby with a birthweight of 2755 g and Apgar scores of 9 at 1 and 5 min. Blisters formed on her heels from her positioning during labour, which healed. Her labial tear, which was not sutured, also healed well. Her baby was bottle‐fed, because blisters formed around her nipples with breastfeeding and expressing milk.
Skeletal muscle dysfunction in COPD. A position paper of the American Society and European Respiratory Society.
Authors: R. Casaburi, R. Gosselink, M. Decramer, P.N.R. Dekhuijzen, M Fournier, M.I. Lewis, F. Maltais, D. Oelberg, M. Reid, J. Roca, A.M.W.J. Schols, G.C. Sieck, D Systrom, P. Wagner, T.J. Williams, E.F.M. Wouters
Journal: American Journal of Respiratory and Critical Care Medicine (1999)
Flammability of paraffin-based products: an under-recognized hazard and methods to reduce it
Authors: F. Al-Niaimi, S. Manickam, N.H. Cox
Journal: British Journal of Dermatology (2010)

Journal Article Flammability of paraffin‐based products: an under‐recognized hazard and methods to reduce it Get access F. Al‐Niaimi, F. Al‐Niaimi Department of Dermatology, Salford Royal Hospital, Stott Lane, Manchester M6 8HD, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. Manickam, S. Manickam Department of Dermatology, Cumberland Infirmary, Carlisle CA2 7HY, U.K.E‐mail: firas55@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar N.H. Cox N.H. Cox Department of Dermatology, Cumberland Infirmary, Carlisle CA2 7HY, U.K.E‐mail: firas55@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 4, 1 April 2010, Pages 893–895, https://doi.org/10.1111/j.1365-2133.2010.09647.x Published: 01 April 2010
The Cot Death Cover-Up?, by Jim Sprott
Authors: Frederik A de Wolff
Journal: BMJ (1997)

Jim Sprott, Penguin Books, £5.99, pp 191 ISBN 0 14 026 198 2

There are a number of syndromes in clinical medicine for which science cannot yet offer a causal explanation, such as the chronic fatigue syndrome. Such syndromes are especially vulnerable for an “alternative” approach. In these instances, chemical factors from the environment are often believed by lay people to be a cause for these diseases, even though there is no scientific evidence for such a relation.

Cot death (the …
Abstract P258: Prevalence of Obesity and Estimated Medical and Work Loss Costs Attributable to High BMI: The Baptist Health South Florida Employee Study
Authors: Khurram Nasir, Emir Veledar, Chukwuemeka Osondu, Ehimen Aneni, Oluseye Ogunmoroti, Sankalp Das, Maribeth Rouseff, Thinh Tran, Don Parris, Leah Holzwarth, Henry Guzman, Theodore Feldman, Michael Ozner, Jonathan Fialkow, Bernie Fernandez, Jack Ziffer, Arthur Agatston
Journal: Circulation (2015)

BACKGROUND: Obesity is strongly related to chronic health problems and concomitant increased healthcare costs for employers. The aim of the study is to explore the distribution of obesity categories and estimate associated health costs among self-insured employees of Baptist Health South Florida (BHSF), a large not-for-profit health care organization. METHODS: Distribution of BMI categories was determined among individuals participating in a voluntary health risk assessment (HRA) available to employees eligible for health benefits. The potential estimates of obesity related costs to BHSF were imputed using CDC's Obesity Cost Calculator based on data from NHIS and MEPS (http://www.cdc.gov/leanworks/costcalculator/disclaimer.html). RESULTS: Overall 9996 (aged 43.1±12.1 years, 75% females, 75% Hispanic, 35% hypertensive, 4% diabetic) employees participated in 2013 annual HRA and wellness fair. The age-adjusted mean BMI was 29.3 (95% CI, 29.1-29.5) for men and 28.3 (95% CI, 28.15-28.45) kg/m2 for women. The table describes distribution of BMI categories according to gender and age groups. The age-adjusted prevalence of obesity (BMI&gt;30 kg/m2) was 36% (95% CI, 34%-37%) among men and 32% (95% CI, 31%-33 %) among women. In BHSF employee population, 6% (n=581) were classified as morbidly obese (BMI&gt;=40) and 7% (n=748) individuals met criteria for bariatric surgery. Total annual estimated cost attributable to high BMI (&gt;25) were $8.05 million (74% medical and 26% work lost) of which 41% were contributed by 14% employees with BMI&gt;35. The average attributable cost per high BMI employee ranged from $598 among those with BMI 25-29.9 to $2695 with BMI&gt;=40. CONCLUSIONS: One third of employees (predominantly female and Hispanic) in a large health care organization (BHSF) were obese. Given the significant financial burden imposed by obesity large self-insured organizations like BHSF have a lot to gain by introducing evidence-driven weight reduction programs, and tracking the success of these programs in the workforce.
Modifiable Behavioral Factors as Causes of Death
Authors: Afschin Gandjour
Journal: JAMA (2004)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 836: Potent antitubulin and antitumor activities influenced by the 3-D conformational shape of bicyclic fused pyrimidines
Authors: Aleem Gangjee, Weiguo Xiang, Susan L. Mooberry, Ernest Hamel
Journal: Cancer Research (2014)

Abstract Compounds that bind to the tubulin colchicine site cause microtubule depolymerization, inhibit the polymerization of purified tubulin and cause cancer cells to accumulate in mitosis. Some colchicine-site agents additionally have the ability to overcome multiple drug resistance mechanisms, including those mediated by the expression of P-glycoprotein (Pgp) or expression of the β-III isotype of tubulin. We have reported a series of aniline substituted pyrimidines and fused bicyclic and tricyclic pyrimidine compounds that bind to the colchicine site. These compounds are single to triple digit nanomolar inhibitors of cancer cell proliferation. We hypothesized that the conformational orientation of the 4-aniline and the fused pyrimidine scaffold plays an important role in the biological activity of these compounds. In this study, we utilized NMR (NOESY) and molecular modeling to compare the lowest energy conformation of different 4-substituted 2-methyl cyclopenta[d]pyrimidines and their microtubule depolymerizing, colchicine site binding and antiproliferative activities. Among the 4-position substituents were N-methyl-4’-methoxynaphthyl-1’-amino (1), N-methyl-6’-methoxynaphthyl-1’-amino (2) and N-methyl-5’-methoxy-2’-amino (3). The IC50 values towards the MDA-MB-435 tumor cell line were 250 nM for 1 and 10 nM for 3. NMR (NOESY) demonstrated that compound 2 lost the free rotation of the naphthyl ring attached to the cyclopenta[d]pyrimidine ring due to 5-H steric hindrance and did not cause microtubule depolymerization. Compounds 1 and 3 retain the ability to rotate the naphthyl ring even though they adopt slightly different stable conformers. The stable conformational differences of these three compounds afford different binding poses in docking to the colchicine site on tubulin (PDB: 1SA0, MOE 2012), which explains the significant differences in antiproliferative activity, microtubule depolymerizing and inhibition of colchicine binding. This study affords a lead compound that defines a 104o (orthogonal) orientation of the naphthyl ring to the cyclopenta[d]pyrimidine scaffold for the best biological activities. Citation Format: Aleem Gangjee, Weiguo Xiang, Susan L. Mooberry, Ernest Hamel. Potent antitubulin and antitumor activities influenced by the 3-D conformational shape of bicyclic fused pyrimidines. [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 836. doi:10.1158/1538-7445.AM2014-836
TREM2 and Parkinson’s Disease
Authors: Bruno A. Benitez, Carlos Cruchaga C
Journal: New England Journal of Medicine (2013)

The finding of a rare non-synonymous variant in TREM2 (p.R47H, rs75932628-T) confers risk for Alzheimer's disease (AD) (odds ratio 2 to 5),1, 2 and the finding that rare variants in other AD-related genes confer risk of several other neurodegenerative diseases,3 prompted us to ask whether R47H confers risk of Parkinson Disease.

Several other observations supported our hypothesis that TREM2 variation may confer susceptibility to Parkinson Disease. TREM2 is expressed mainly on microglia in the central nervous system and seems to mediate the phagocytosis of apoptotic neurons through TREM2 ligation4. Microgliosis has been implicated in the pathogenesis of Parkinson’s disease (PD), a neurological disorder characterized by degeneration of dopaminergic neurons in the substantia nigra (SN) pars compacta. Dopaminergic neurons express ligands that interact directly with TREM24 and, TREM2 mRNA levels in the SN are the second highest among all brain regions1. In addition, pathological findings of TREM2 variant carriers have shown the presence of abundant Lewy-bodies1, the hallmark of PD.

We directly genotyped rs75932628, encoding the R47H variant, in 478 PD patients and 837 healthy individuals from the Washington University in Saint Louis Movement Disorder Clinic5 as well as in 654 PD patients and 550 controls from the Memory Disorders Unit, Clinica Universidad de Navarra, School of Medicine (Pamplona, Spain)2. PD diagnosis was established according to the UK Brain Bank criteria. We found three p.R47H heterozygous carriers among the US PD cases and six among the Spanish PD cases, but in none of the screened controls (Table 1). The p.R47H variant is associated with PD in both the US (p=0.02) and in the Spanish sample (p=0.02). The combined analysis confirmed the association p.R47H variant with PD (p=4.7 × 10−3). These results suggest that the p.R47H variant not only increases risk for AD but for PD as well.



Table 1

Association between the rs75932628-T Variant and Parkinson's Disease in two samples with different genetic background
289. Cisplatin and Doxorubicin Enhance the Activity of the CRAd Ad5-Δ24RGD Against Osteosarcoma Cell Lines but Not Primary Osteosarcoma Cells
Authors: Dinja Oosterhoff, Victor W. van Beusechem, Epie Boven, Herbert M. Pinedo, Winald R. Gerritsen
Journal: Molecular Therapy (2004)

Conditionally replicating adenoviruses (CRAds) selectively replicate in and thereby kill cancer cells. CRAds have shown limited efficacy as single modality treatment in clinical trials. Combining CRAds with conventional chemotherapy can result in synergistic efficacy in a range of tumor types, as demonstrated in several studies. Oxaliplatin is a derivative of cisplatin with higher activity against colon cancer cells and was recently approved for the treatment of colorectal cancer. Here, we investigated combination treatment in human colon cancer cell lines using oxaliplatin and two CRAds, i.e., AdΔ24 that selectively replicates in cancer cells with a defective pRb pathway and its p53-expressing derivative AdΔ24-p53 with enhanced oncolytic potency.
Phase I Trial of Sorafenib Following Liver Transplantation in Patients with High-Risk Hepatocellular Carcinoma
Authors: Abby B. Siegel, Anthony B. El-Khoueiry, Richard S. Finn, Katherine A. Guthrie, Abhishek Goyal, Alan P. Venook, Charles D. Blanke, Elizabeth C. Verna, Lorna Dove, Jean Emond, Tomoaki Kato, Benjamin Samstein, Ronald Busuttil, Helen Remotti, Amy Coffey, Robert S. Brown Jr
Journal: Liver Cancer (2015)

Liver transplantation offers excellent long-term survival for hepatocellular carcinoma (HCC) patients who fall within established criteria. For those outside such criteria, or with high-risk pathologic features in the explant, HCC recurrence rates are higher. We conducted a multicenter phase I trial of sorafenib in liver transplantation patients with high-risk HCC. Subjects had HCC outside the Milan criteria (pre- or post-transplant), poorly differentiated tumors, or vascular invasion. We used a standard 3+3 phase I design with a planned duration of treatment of 24 weeks. Correlative studies included the number of circulating endothelial cells (CECs), plasma biomarkers, and tumor expression of p-Erk, p-Akt, and c-Met in tissue micro-arrays. We enrolled 14 patients with a median age of 63 years. Of these, 93% were men and 71% had underlying hepatitis C virus (HCV) and 21% had HBV. The maximum tolerated dose of sorafenib was 200 mg BID. Grade 3-4 toxicities seen in &gt;10% of subjects included leukopenia (21%), elevated gamma-glutamyl transferase (21%), hypertension (14%), hand-foot syndrome (14%) and diarrhea (14%). Over a median follow-up of 953 days, one patient died and four recurred. The mean CEC number at baseline was 21 cells/4 ml for those who recurred, and 80 cells/4 ml for those who did not (p=0.10). Mean soluble vascular endothelial growth factor receptor-2 levels decreased after 1 month on sorafenib (p=0.09), but did not correlate with recurrence. There was a trend for tumor c-Met expression to correlate with increased risk of recurrence. Post-transplant sorafenib was found to be feasible and tolerable at 200 mg PO BID. The effect of post-transplant sorafenib on recurrence-free survival is potentially promising but needs further validation in a larger study.
Metabolic bone disease in childrenClinical Pediatrics Series, Volume 6. Edited by Salvador Castells and Laurence Finberg. New York: Marcel Dekker, 1990, $99.75 U.S. and Canada, $119.50 all other countries (xv + 386 pages). ISBN 0-8247-8153-8
Authors: Thomas O. Carpenter
Journal: Trends in Endocrinology and Metabolism (1990)