tbuckley/cabot-search huggingface dataset:
Imported diphyllobothriasis in Switzerland: molecular methods to define a clinical case of Diphyllobothrium infection as Diphyllobothrium dendriticum, August 2010
Authors: F de Marval, B Gottstein, M Weber, B Wicht
Journal: Eurosurveillance (2013)

Following a first clinical case of infection by Diphyllobothrium dendriticum in Switzerland in 2006, we report a second case in the country. The species was identified by molecular methods. In the Swiss, French and Italian subalpine regions, human diphyllobothriasis has seen a comeback since the late 1980's, and Diphyllobothrium latum is usually considered the causative agent of the disease. In addition, several locally acquired and imported clinical infections due to allochthonous Diphyllobothrium species have been documented in the last years. Due to the colonisation potential of these parasites and their probably underestimated presence in the human population, there is a need for discriminating them at the medical laboratory level. Because the morphological characters are very similar among the different taxa, a correct identification requires the use of molecular methods. Molecular identification would improve diagnosis and help monitor the distribution of Diphyllobothrium species in Europe.
Selective suppression of dendritic cell functions by <i>Mycobacterium ulcerans</i> toxin mycolactone
Authors: Emmanuelle Coutanceau, Jeremie Decalf, Angelo Martino, Aurélie Babon, Nathalie Winter, Stewart T. Cole, Matthew L. Albert, Caroline Demangel
Journal: The Journal of Experimental Medicine (2007)

Mycolactone is a polyketide toxin produced by Mycobacterium ulcerans (Mu), the causative agent of the skin disease Buruli ulcer (BU). Surprisingly, infected tissues lack inflammatory infiltrates. Structural similarities between mycolactone and immunosuppressive agents led us to investigate the immunomodulatory properties of mycolactone on dendritic cells (DCs), the key initiators and regulators of immune responses. At noncytotoxic concentrations, phenotypic and functional maturation of both mouse and human DCs was inhibited by mycolactone. Notably, mycolactone blocked the emigration of mouse-skin DCs to draining lymph nodes, as well as their maturation in vivo. In human peripheral blood–derived DCs, mycolactone inhibited the ability to activate allogeneic T cell priming and to produce inflammatory molecules. Interestingly, production of the cytokines interleukin (IL) 12, tumor necrosis factor α, and IL-6 was only marginally affected, whereas production of the chemokines macrophage inflammatory protein (MIP) 1α, MIP-1β, regulated on activation, normal T cell expressed and secreted, interferon γ–inducible protein 10, and monocyte chemoattractant protein 1 was abolished at nanomolar concentrations. Importantly, mycolactone endogenously expressed by Mu mediated similar inhibitory effects on β-chemokine production by DCs. In accordance with the histopathological features of BUs, our results suggest that bacterial production of mycolactone may limit both the initiation of primary immune responses and the recruitment of inflammatory cells to the infection site. Moreover, they highlight a potential interest in mycolactone as a novel immunosuppressive agent.
Minigene analysis of intronic variants in common SPINK1 haplotypes associated with chronic pancreatitis
Authors: E Kereszturi, O Kiraly, M Sahin-Toth
Journal: Gut (2008)

<h3>Background and aims:</h3> Two common haplotypes of the serine protease inhibitor Kazal type 1 (<i>SPINK1</i>) gene have been shown to increase the risk for chronic pancreatitis. A haplotype comprising the c.101A&gt;G (p.N34S) missense variant and four intronic alterations has been found worldwide, whereas a second haplotype consisting of the c.−215G&gt;A promoter variant and the c.194+2T&gt;C intronic alteration has been observed frequently in Japan. <h3>Methods:</h3> In the present study, the functional significance of the intronic variants in the pathogenic <i>SPINK1</i> haplotypes was examined by utilising minigenes, which harbour individual introns placed in the appropriate context of the full-length <i>SPINK1</i> cDNA. Cells transfected with the <i>SPINK1</i> minigenes secrete active trypsin inhibitor, thereby allowing evaluation of mutational effects simultaneously on transcription, splicing, translation and secretion. <h3>Results:</h3> It was found that the c.194+2T&gt;C intronic alteration abolished SPINK1 expression at the mRNA level, with consequent loss of inhibitor secretion, whereas the p.N34S-associated intronic variants had no detectable functional effect. <h3>Conclusions:</h3> Taken together with previous studies, the results indicate that all known variants within the p.N34S-associated haplotype are functionally innocuous, suggesting that an as yet unidentified variant within this haplotype is responsible for the pathogenic effect. The marked negative impact of the c.194+2T&gt;C variant on SPINK1 expression supports the notion that SPINK1 variants increase the risk of chronic pancreatitis by diminishing protective trypsin inhibitor levels.
Diabetes Overtreatment in Elderly Individuals
Authors: Mary A. Andrews, Patrick G. O’Malley
Journal: JAMA (2014)

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
Smad3 Deficiency Promotes Tumorigenesis in the Distal Colon of <i>ApcMin/+</i> Mice
Authors: Nicole M. Sodir, Xuan Chen, Ryan Park, Andrea E. Nickel, Peter S. Conti, Rex Moats, James R. Bading, Darryl Shibata, Peter W. Laird
Journal: Cancer Research (2006)

Colorectal cancer, one of the most common human malignancies in the Western world, is often subdivided based on tumor location in either the distal or proximal colon. Several mouse models have been developed to study human colorectal cancer, but few display this clear distinction between the two colonic locations. By crossing Apc(Min/+) and Smad3 mutant mice, we showed that combined activation of the Wnt pathway and attenuation of the transforming growth factor-beta (TGF-beta) pathway causes high multiplicity and rapid onset of invasive tumorigenesis almost exclusively in the distal colon, closely mimicking the familial adenomatous polyposis (FAP) disease and consisting with distinct colorectal cancer etiologies based on tumor location. Transcriptional profiling revealed higher expression of several TGF-beta activators in the normal distal mucosa than in proximal mucosa, suggesting a stronger reliance on TGF-beta-mediated growth control in the distal than in the proximal colon. Apc(Min/+)Smad3(-/-) mice provide an alternative model to Apc(Min/+) mice to study FAP and distal sporadic colorectal cancer. This model will be useful in dissecting mechanistic and etiologic differences between proximal and distal colonic cancer, whereas the confinement of tumorigenesis to the distal colon offers unique advantages in monitoring tumor progression by in vivo imaging.
Cardiac Catheterization in Patients With Unstable Angina
Authors: Gary D. Plotnick
Journal: JAMA (1980)

Among patients with unstable angina pectoris, those with crescendo angina seem to be at high risk for death and myocardial infarction. We reviewed the clinical, arteriographic, and hemodynamic findings in 218 consecutive catheterized patients with unstable angina. Unstable angina was defined as ischemic cardiac pain at rest associated with transient ECG changes but no evidence for acute myocardial infarction. Patients were divided into two groups according to the duration of symptoms: 134 patients with crescendo angina (new, or increasing, rest pain with previous ischemic symptoms present for more than three months) and 84 with recent onset angina (symptoms present for less than three months). Compared with patients with recent onset symptoms, patients with crescendo angina had more extensive coronary disease and lower ejection fractions, which may explain their poor prognosis.
Positive darwinian selection observed at the variable-region genes of immunoglobulins.
Authors: T Tanaka, M Nei
Journal: Molecular Biology and Evolution (1989)

To examine Gojobori and Nei's hypothesis that the immunoglobulin heavy-chain variable-region (VH) genes in mammals are subject to diversity-enhancing selection, we studied the rates of synonymous and nonsynonymous nucleotide substitution in the complementarity-determining regions (CDRs) and in the framework regions (FRs) of mouse and human VH genes. The results obtained indicate that the non-synonymous rate is higher than the synonymous rate in CDRs, whereas the reverse is true in FRs. This observation supports Gojobori and Nei's hypothesis and suggests that diversity-enhancing selection (similar to overdominant selection) operates mainly in CDRs and that this is one of the evolutionary factors that increase antibody diversity.
Central Role of Connexin40 in the Propagation of Electrically Activated Vasodilation in Mouse Cremasteric Arterioles In Vivo
Authors: Xavier F. Figueroa, David L. Paul, Alexander M. Simon, Daniel A. Goodenough, Kathy H. Day, David N. Damon, Brian R. Duling
Journal: Circulation Research (2003)

When a short segment of arteriole is stimulated, vasomotor responses spread bidirectionally along the vessel axis purportedly via gap junctions. We used connexin40 knockout (Cx40-/-) mice to study vasomotor responses induced by 10-second trains of electrical stimulation (30 Hz, 1 ms, 30 to 50 V) in 2nd or 3rd order arterioles of the cremaster muscle. Measurements were made at the stimulation site (local) and at conducted sites (500, 1000, and 2000 microm upstream). In wild-type (Cx40+/+) animals, electrical stimulation evoked a local vasoconstriction and a conducted vasodilation that spread very rapidly along the vessel length without detectable decay. In Cx40-/- mice, the conducted dilation was converted into either vasoconstriction or a slowly developing vasodilation that decayed along the vessel length. Tetrodotoxin (TTX, 1 micromol/L) had no effect on the local vasoconstriction in either Cx40+/+ or Cx40-/- mice, but enhanced the conducted vasodilation in Cx40+/+ animals. In Cx40-/- mice, TTX abolished the conducted vasoconstriction when present and revealed a small vasodilation that decayed with distance. In the group of Cx40-/- mice in which electrical stimulation elicited a conducted vasodilation, TTX had no effect. Immunocytochemistry revealed Cx40 only in the endothelial layer of arterioles from Cx40+/+ mice and complete elimination of this connexin in the Cx40-/- animals. These results indicate that focal current stimulation causes vasoconstriction by a combination of perivascular nerve stimulation and smooth muscle activation. Moreover, electrical stimulation activates a nonneuronal, Cx40-dependent vasodilator response that spreads along the vessel length without decay.
Follicular cutaneous squamous cell carcinoma: an under-recognized neoplasm arising from hair appendage structures
Authors: I. Shendrik, A.N. Crowson, C.M. Magro
Journal: British Journal of Dermatology (2013)

Cutaneous squamous cell carcinoma (SCC) with no demonstrable point of epidermal origin is problematic as it raises consideration of metastatic SCC histologically. There are rare case reports and series of SCC arising from the wall of hair follicle structures. Such lesions have been termed follicular SCC (FSCC).To investigate the clinicopathological features of FSCC.We prospectively collected cases of follicular SCC over a 5-year period. Follicular SCC is defined as a cutaneous SCC deriving from a pre-existing hair follicle structure. Lesions were considered to represent 'hybrid' SCCs if an interfollicular epidermal origin was also demonstrated; SCCs with > 50% of the origin from interfollicular epidermis were excluded. Histological features and clinical information were evaluated.We identified 61 cases of follicular SCC arising in 60 patients from a database of 5212 cutaneous SCCs encountered over the same time period by the same authors. There were 49 pure follicular SCCs and 12 hybrid lesions. The male to female ratio was 44 : 16; the mean age was 74 years (range 44-93). Follicular SCC represents 1·2% of all primary SCCs. Biopsies of such lesions, if the appendage structure of origin is not represented, are histologically indistinguishable from metastatic SCC.Recognition of this under-reported form of SCC is essential if an inappropriate diagnosis of metastatic SCC, with potentially harmful and inappropriate therapy and investigation, is to be avoided.
Mucus transportability: the bovine trachea and frog palate models compared
Authors: PJ Wills, K Pritchard, PJ Cole
Journal: European Respiratory Journal (1998)

For nearly 30 yrs, the mucus-depleted frog palate has been used to measure the ciliary transportability of respiratory and other mucus gels, but the data obtained from this amphibian digestive system may not be applicable to human airway mucociliary clearance. This study compared this model with the mucus-depleted bovine trachea, a mammalian respiratory system. Assessments were made of the reproducibility of each model, and of the behaviour of sputum subjected to changes to its salinity or hydration. The bovine tracheal model was more reproducible than the frog palate. On the trachea but not the frog palate, sputum was transported more slowly than mucus from healthy animals. Increasing the salinity of sputum caused it to be transported 129% more quickly by the trachea (p=.001), but made no significant change to its transportability by the frog palate. Removal of water by evaporation led to an 83% increase in its bovine tracheal transportability but a 60% fall in its frog palate transportability (p<0.001). Therefore, the models make opposite predictions for the clinical value of altering mucus osmolality. The applicability of the frog palate model in the study of airway mucociliary clearance should be seriously questioned.
Successful treatment of refractory Hailey-Hailey disease with a 595-nm pulsed dye laser: A series of 7 cases
Authors: Katherine M. Hunt, J. Daniel Jensen, Stephanie B. Walsh, Mary E. Helms, Vera Y. Soong, Elizabeth S. Jacobson, Naveed Sami, Conway C. Huang, Amy Theos, Marian E. Northington
Journal: Journal of the American Academy of Dermatology (2015)
Clonotype Analysis of Cytomegalovirus-Specific Cytotoxic T Lymphocytes
Authors: Nina Babel, Gordon Brestrich, Lukasz P. Gondek, Arne Sattler, Marcin W. Wlodarski, Nina Poliak, Nicole Bethke, Andreas Thiel, Markus H. Hammer, Petra Reinke, Jaroslaw P. Maciejewski
Journal: Journal of the American Society of Nephrology (2008)

Cytotoxic T lymphocytes (CTL) control the replication of human cytomegalovirus (CMV). Previous studies assessed the clonotypic composition of CTL specific for individual immunodominant peptides within a certain HLA context. Such an approach has inherent limitations and may not assess the true clonal CTL response in vivo. Here, the clonotypic composition of CMV-specific CTL was determined in HLA-A2, CMV-seropositive kidney transplant recipients and healthy blood donors after stimulation of peripheral blood mononuclear cells with either a pp65 whole-peptide pool or a single immunodominant peptide. Even after stimulation with the whole peptide pool, CMV-specific CTL remained monoclonal or oligoclonal. Regarding intraindividual variation, the CDR3 motifs of the dominant clones were identical to those observed in CTL generated by the single immunodominant peptide. Sequencing of the CDR3 regions demonstrated significant interindividual variation; however, structural homology was observed for immunodominant clonotypes in three individuals. In conclusion, the highly focused T cell receptor repertoire found after stimulation with either a single immunodominant peptide or a peptide pool demonstrates a pivotal role for immunodominant epitopes in the generation of a clonal repertoire. These results provide new insights into the regulation of CMV clonal dominance and may contribute to the design and monitoring of adoptive immunotherapy.
Oncogenic <i>KRAS</i> and <i>BRAF</i> Differentially Regulate Hypoxia-Inducible Factor-1α and -2α in Colon Cancer
Authors: Hirotoshi Kikuchi, Maria S. Pino, Min Zeng, Senji Shirasawa, Daniel C. Chung
Journal: Cancer Research (2009)

Abstract KRAS and BRAF mutations are frequently observed in human colon cancers. These mutations occur in a mutually exclusive manner, and each is associated with distinctive biological features. We showed previously that K-ras can interact with hypoxia to activate multiple signaling pathways. Many hypoxic responses are mediated by hypoxia-inducible factor (HIF)-1α and HIF-2α, and we sought to define the roles of mutant KRAS and BRAF in the induction of HIF-1α and HIF-2α in colon cancer cells. Ectopic expression of mutant K-ras in Caco2 cells enhanced the hypoxic induction of only HIF-1α, whereas mutant BRAF enhanced both HIF-1α and HIF-2α. Knockout or knockdown of mutant KRAS in DLD-1 and HCT116 cells impaired the hypoxic induction of only HIF-1α. HIF-1α mRNA levels were comparable in cells with and without a KRAS mutation. However, the rate of HIF-1α protein synthesis was higher in cells with a KRAS mutation, and this was suppressed by the phosphoinositide 3-kinase inhibitor LY294002. In contrast, knockdown of mutant BRAF in HT29 cells suppressed both HIF-1α and HIF-2α. Although BRAF regulated mRNA levels of both HIF-1α and HIF-2α, knockdown of BRAF or treatment with the MEK inhibitor PD98059 impaired the translation of only HIF-2α. Our data reveal that oncogenic KRAS and BRAF mutations differentially regulate the hypoxic induction of HIF-1α and HIF-2α in colon cancer, and this may potentially contribute to the phenotypic differences of KRAS and BRAF mutations in colon tumors. [Cancer Res 2009;69(21):8499–506]
Estrogen Receptor, Progesterone Receptor, Human Epidermal Growth Factor Receptor 2 (HER2), and Epidermal Growth Factor Receptor Expression and Benefit From Lapatinib in a Randomized Trial of Paclitaxel With Lapatinib or Placebo As First-Line Treatment in HER2-Negative or Unknown Metastatic Breast Cancer
Authors: Richard S. Finn, Michael F. Press, Judy Dering, Michael Arbushites, Maria Koehler, Cristina Oliva, Lisa S. Williams, Angelo Di Leo
Journal: Journal of Clinical Oncology (2009)

Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) with activity in HER2-amplified metastatic breast cancer (MBC). Its role in non-HER2-amplified MBC remains unclear. EGF30001, a phase III trial of lapatinib and paclitaxel versus paclitaxel and placebo, demonstrated lapatinib does not significantly benefit HER2-negative or HER2-unselected patients with MBC. Published data support interactions between steroid hormone and peptide growth factor signaling. We hypothesized that molecular subgroups may exist within EGF30001 that would benefit from lapatinib.A blinded, retrospective biomarker evaluation was performed using immunohistochemistry to semiquantitate estrogen (ER), progesterone (PR), and EGFR expression. HER2 amplification was determined by fluorescent in situ hybridization. Effects of these biomarkers on event-free survival (EFS) were examined in patients with available tissue (n = 493).Lapatinib improved median EFS in HER2-amplified, ER- or PR-positive MBC (n = 36; 5.7 v 4.5 months; P = .351); benefit was greater and statistically significant in HER2-amplified, ER-negative, PR-negative MBC (n = 42; 8.3 v 5.0 months; P = .007). In HER2-negative, ER-positive MBC, median EFS improvement varied by degree of PR expression (H-score): no benefit if PR-strong (n = 133; 9.3 v 7.3 months; P = .373), benefit if PR-weak (n = 50; 7.3 v 2.4 months; P = .026), and potential antagonism if PR-negative (n = 40; 3.7 v 7.2 months; P = .004). No benefit was seen in triple-negative MBC (n = 131; median EFS, 4.6 v 4.8 months; P = .255). EGFR expression was not correlated with benefit from lapatinib.Although subgroups are small, these analyses support the hypothesis that semiquantitative determination of hormone receptor status may be a surrogate for EGFR and/or HER2 dependency.
Variability in Activity May Precede Diabetic Foot Ulceration
Authors: David G. Armstrong, Lawrence A. Lavery, Katherine Holtz-Neiderer, Martha J. Mohler, Christopher S. Wendel, Brent P. Nixon, Andrew J.M. Boulton
Journal: Diabetes Care (2004)

OBJECTIVE—To evaluate the role of activity in the development of neuropathic foot ulceration in individuals with diabetes. RESEARCH DESIGN AND METHODS—We evaluated the first 100 consecutive individuals with diabetes (95.0% male, aged 68.5 ± 10.0 years with concomitant neuropathy, deformity, and/or a history of lower-extremity ulceration/partial foot amputation) enrolled in an ongoing prospective longitudinal activity study. Subjects used a high-capacity continuous computerized activity monitor. Data were collected continuously over a minimum of 25 weeks (or until ulceration) with daily activity units expressed as means ± SD. RESULTS—Eight subjects ulcerated during the evaluation period of 37.1 ± 12.3 weeks. The average daily activity was significantly lower in individuals who ulcerated compared with individuals who did not ulcerate (809.0 ± 612.2 vs. 1,394.5 ± 868.5, P = 0.03). Furthermore, there was a large difference in variability between groups. The coefficient of variation was significantly greater in the ulceration group compared with the no ulceration group (96.4 ± 50.3 vs. 44.7 ± 15.4%, P = 0.0001). In the 2 weeks preceding the ulcerative event, the coefficient of variation increased even further (115.4 ± 43.0%, P = 0.02), but there was no significant difference in average daily activity during that period (P = 0.5). CONCLUSIONS—The results of this study suggest that individuals with diabetes who develop ulceration may actually have a lower overall activity than their counterparts with no ulceration, but the quality of that activity may be more variable. Perhaps modulating the “peaks and valleys” of activity in this population through some form of feedback might prove to reduce risk for ulceration in this very-high-risk population.