tbuckley/cabot-search huggingface dataset:
Abstract 3227: JNK2 oligomerization regulates its activation through non-canonical pathways
Authors: Tamer S. Kaoud, Austin F. Riggs, Kevin N. Dalby
Journal: Cancer Research (2014)

Abstract C-Jun N-terminal kinases (JNKs) regulate various cellular functions. Their activation is mediated cooperatively by both MKK4 and MKK7. The c-Jun N-terminal kinase 2 (JNK2) isoform is constitutively activated in glial tumor cell lines and human glioblastoma models. We investigated the regulation of JNK2 self-activation in vitro in both cell-free and cell-based experiments. Light scattering analysis suggested that unphosphorylated recombinant JNK2α2 exists in solution as a mixture of monomers, dimers and tetramers. JNK2α2 self-phosphorylates more rapidly in vitro when assayed at low concentration leading to its activation. However, at a slightly higher concentration, the formation of a tetramer is favored, whose ability to self-phosphorylate is suppressed. HEK293T cells that were transfected with varying amounts of pcDNA-JNK2α2 showed that an increased concentration of JNK2α2 (54 kDa) could suppress the appearance of activated JNK2α2 in mammalian cells. A mutant of JNK2 (F170R) thought to stabilize the DFG-out conformation appears to stabilize the formation of a JNK2 tetramer. Taken together our data suggest that oligomerization may regulate non-canonical (self-activation) activation of JNK2. Citation Format: Tamer S. Kaoud, Austin F. Riggs, Kevin N. Dalby. JNK2 oligomerization regulates its activation through non-canonical pathways. [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 3227. doi:10.1158/1538-7445.AM2014-3227
Cat-scratch Disease and Bacillary Angiomatosis
Authors: Richard M. Tucker
Journal: JAMA (1991)

To the Editor.  —Dr Holley1has reported apparent successful treatment of CSD, typically a self-limited syndrome, with orally administered ciprofloxacin. The purported causal agent of CSD was first visualized in the lymph nodes of patients with the classic clinical syndrome in 1983.2A similar or related organism has been visualized in the cutaneous and disseminated lesions of epithelioid angiomatosis in patients with HIV infection and the acquired immunodeficiency syndrome.3Although the staining characteristics and morphologic features of the two organisms are similar, the relatedness of these organisms has yet to be determined and their antibiotic susceptibility profiles may differ. We report the occurrence of epithelioid angiomatosis despite recent prolonged therapy with orally administered ciprofloxacin.  Report of a Case.  —The patient, a 37-year-old homosexual white man with HIV infection, had a 3-month history of fever, weight loss, splenomegaly, and pancytopenia. A recent CD4 count was less than 10/mm3
Interferon γ inhibits growth of human pancreatic carcinoma cells via caspase-1 dependent induction of apoptosis
Authors: K M Detjen, K Farwig, M Welzel, B Wiedenmann, S Rosewicz
Journal: Gut (2001)

BACKGROUND AND AIMS The poor prognosis of pancreatic cancer is partly due to resistance to a broad spectrum of apoptotic stimuli. To identify intact proapoptotic pathways of potential clinical relevance, we characterised the effects of interferon γ (IFN-γ) on growth and survival in human pancreatic cancer cells. METHODS IFN-γ receptor expression and signal transduction were examined by reverse transcriptase-polymerase chain reaction (RT-PCR), immunoprecipitation, western blot analysis, and transactivation assays. Effects on cell growth and survival were evaluated in terms of cell numbers, colony formation, cell cycle analysis, DNA fragmentation, and poly(ADP ribose) polymerase (PARP) cleavage. RESULTS All four pancreatic cancer cell lines examined expressed functional IFN-γ receptors and downstream effectors, including the putative tumour suppressor interferon regulatory factor 1 (IRF-1). IFN-γ treatment profoundly inhibited anchorage dependent and independent growth of pancreatic cancer cells. Cell cycle analyses revealed subdiploid cells suggesting apoptosis, which was confirmed by demonstration of DNA fragmentation and PARP cleavage. Time and dose dependency of apoptosis induction and growth inhibition correlated closely, identifying apoptosis as the main, if not exclusive, mechanism responsible for growth inhibition. Apoptosis was preceded by upregulation of procaspase-1 and accompanied by proteolytic activation. Furthermore, the caspase inhibitor z-vad-fmk completely prevented IFN-γ mediated apoptosis. CONCLUSIONS These results identify an intact proapoptotic pathway in pancreatic cancer cells and suggest that IRF-1 and/or procaspase-1 may represent potential therapeutic targets to be further explored.
Focal Nodular Hyperplasia of the Liver and Intrahepatic Hemorrhage in Young Women on Oral Contraceptives
Authors: J. Q. STAUFFER
Journal: Annals of Internal Medicine (1975)

Focal nodular hyperplasia of the liver may occur with increased frequency in young women who have been taking oral contraceptives. Patients may present with massive intraperitoneal hemorrhage requiring immediate surgical intervention. These nodules may be multiple and occasionally pedunculated, mimicking ovarian cysts. Liver function tests are nondiagnostic. A liver scan and arteriogram are often helpful in determining a diagnosis. Percutaneous liver biopsy is contraindicated. Large nodules should be resected, and continued use of oral contraceptives is contraindicated.
Mercury-induced autoimmunity in mice.
Authors: Jesper Bo Nielsen, Per Hultman
Journal: Environmental Health Perspectives (2002)

We have studied the effect of gender, genetics, and toxicokinetics on immune parameters in mercury-induced autoimmunity in mice. Data strongly suggest that the mechanism for mercury-induced autoimmunity involves modification of the autoantigen fibrillarin by mercury followed by a T-cell-dependent immune response driven by the modified fibrillarin. Mice with different H-2 haplotypes were treated with (203)HgCl(2) in a dose of 0.5-16 mg Hg/L drinking water for 10 weeks. Whole-body accumulation and renal accumulation of mercury were assessed. Serum antinuclear antibodies were used to evaluate the autoimmune response, and serum immunoglobulin E (IgE) to study effects on T-helper cells of type 2. Strains with a susceptible H-2 haplotype developed autoantibodies to the nucleolar protein fibrillarin (AFA) in a dose-dependent pattern within 2 weeks. The substantially lower whole-body and organ mercury level needed to induce AFA in the susceptible A.SW strain compared with the H-2 congenic B10.S strain demonstrates that genetic factors outside the H-2 region modify the autoimmune response. Mouse strains without the susceptible haplotype did not develop any autoimmune reaction irrespective of dose and organ deposition of mercury. In susceptible mouse strains, males and females had different thresholds for induction of autoimmune reactions. In susceptible strains, serum IgE increased dose dependently and reached a maximum after 1-2.5 weeks. A susceptible H-2 haplotype is therefore a prerequisite for the autoimmune response. Mercury exposure will modulate the response, qualitatively through the existence of dose-related thresholds for autoimmune response and quantitatively as increasing doses cause increasing autoimmune response. Further, gender and non-H-2 genes modulate both the induction and subsequent development of AFA. Induction of IgE seems not to be mechanistically linked to the AFA response.
Consensus on 'rational approach' to therapy of childhood febrile seizures
Authors: John Elliott
Journal: JAMA (1980)

Each year in the United States, 500,000 children between the ages of 3 months and 5 years will experience convulsions related to fever. The cause of these so-called febrile seizures remains unknown, and questions over how best to treat and prevent them are a source of confusion to both physicians and frightened parents. This poorly understood disorder was the target of a consensus development panel recently convened by the National Institutes of Health (NIH).  According to the panel, chaired by Edwin L. Kendig, MD, professor of pediatrics at the Medical College of Virginia of Virginia Commonwealth University, Richmond, a majority (60% to 70%) of children who experience one febrile seizure will not suffer a subsequent one and do not require long-term treatment. However, in a group of patients designated as high risk, prolonged anticonvulsant therapy should be considered despite the risk of drug-related side effects.  The panel also sought to
Involvement of the CD95 (APO-1/Fas) receptor and ligand system in Helicobacter pylori-induced gastric epithelial apoptosis.
Authors: J Rudi, D Kuck, S Strand, A von Herbay, S M Mariani, P H Krammer, P R Galle, W Stremmel
Journal: Journal of Clinical Investigation (1998)

Helicobacter pylori infection is associated with chronic gastritis, peptic ulceration, and gastric carcinoma. The potential role of CD95-mediated apoptosis was investigated in a panel of gastric biopsies obtained from patients with H. pylori-associated chronic gastritis (n = 29) and with noninfected normal mucosa (n = 10). Immunohistochemistry revealed increased CD95 receptor expression in epithelial and lamina propria cells in chronic gastritis. By in situ hybridization, CD95 ligand mRNA was absent or low in normal mucosa but expressed at high levels in lamina propria lymphocytes and, unexpectedly, in epithelial cells in chronic gastritis. Apoptotic cells were rare in normal mucosa but were observed regularly in chronic gastritis in close proximity to CD95 ligand mRNA expression throughout the epithelial and lamina propria cells. In a functional analysis gastric epithelial cell lines were incubated with supernatants of H. pylori. Treatment with the cytotoxic isolate H. pylori 60190 but not with the noncytotoxic isolate Tx30a upregulated CD95 in up to 50% of gastric epithelial cells and induced apoptosis in these cells. H. pylori-induced apoptosis was partially prevented by blocking CD95, demonstrating the functional role of the CD95 system. These findings suggest that H. pylori-associated chronic gastritis involves apoptosis of gastric epithelial cells by activation of the CD95 receptor and ligand system.
Isolated Vasculitis of the Stomach: A Novel or Rare Disease with a Difficult Differential Diagnosis
Authors: U Will, R Gerlach, I Wanzar, H Urban, T Manger, F Meyer
Journal: Endoscopy (2006)

In up to 80 % of patients with vasculitis, signs of the disease are also seen in the gastrointestinal tract. However, no cases of exclusively gastric vasculitis have previously been reported. We report here the case of a 45-year-old woman with upper abdominal discomfort (no arthropathy), with gastroscopic and endoscopic ultrasound (EUS) findings that mimicked scirrhous gastric carcinoma. Gastroscopy revealed giant gastric folds and a suspicious antral ulcer (with histological findings suggesting chronic active pangastritis). EUS showed a concentric, thickened gastric wall (8 mm) with ”pseudolamellation“ and more than five enlarged lymph nodes in the paragastric region (lesser curvature). On the basis of suspected scirrhous gastric carcinoma, the patient underwent a four-fifths gastric resection of the altered parts of the gastric tissue. The postoperative course was uneventful. Histological examination of the specimen revealed severe obliterative panvasculitis of the stomach. During a 22-month follow-up period, no signs or symptoms of systemic primary or secondary vasculitis were found in the patient’s medical history, symptoms, laboratory parameters, or imaging.This case shows for the first time that a specific gastric panvasculitis can occur, either as a preliminary stage of the condition or as a distinct manifestation of vasculitis associated with the stomach alone. Gastric resection appears to be indicated in patients with isolated obliterative gastric vasculitis, since it avoids the side effects of long-term immunosuppressive therapy and provides prognostic information that takes account of the differential diagnosis of scirrhous gastric carcinoma.
Post-Irradiation Fractures
Authors: Edwin L. Lame
Journal: JAMA (1961)

<h3>To the Editor:—</h3> Twenty years ago femoral neck necrosis following irradiation of the female pelvis for cancer was not rare and could be excused in those practitioners whose training antedated the modern teaching of radiation therapy. Today, no such excuse is valid, or fair to the public. In fact, it is shocking to read inThe Journal, Jan. 21, p. 204, that 24 postirradiation fractures of the femur can be collected at the Mayo Clinic. Praise be to them for successful treatment. Perhaps they will assist in broadcasting to their far-flung physician contributors a message: Pelvic x-radiation, whether administered by radiologist or gynecologist, should be given only after careful and accurate localization of portals (by fluoroscopy or test films) and placement of protective lead blockers over the femoral heads and necks. I know this can be done with safety, because our program has used for 15 years one of the
Seizure Associated with Use of Visicol for Colonoscopy
Authors: Martin Rose, Leonard S. Jacob
Journal: New England Journal of Medicine (2002)

Myers et al. (March 14 issue) 1 report that in their study, exercise capacity was a stronger predictor of mortality than other established risk factors, after adjustment for several clinical variables.In an earlier article in the Journal , Cole et al. stressed the importance of recovery of the heart rate after exercise; in an analysis adjusted for many confounding variables, a low value for heart-rate recovery, defined as a reduction of 12 beats per minute or less from the heart rate at peak exercise (symptom-limited), was predictive of death from all causes (adjusted relative risk, 2.0; P<0.001). 2 The same authors stated that in an analysis adjusted for age and sex, the heart rate at rest, before exercise, was predictive of the risk of death (hazard ratio, 1.29; P<0.001). 3 In the group of normal subjects studied by Myers et al., the resting heart rate was much higher in the subjects who died than in those who survived (P<0.001), 1 but neither the resting heart rate nor heart-rate recovery after exercise was included in the multivariate regression analysis of mortality.The heart rate, especially during recovery, is a good marker of physical fitness, 4 as demonstrated in the study by Cole et al.Thus, it is possible that inclusion of the heart rate as a variable would exclude exercise capacity from the Cox proportional-hazards model in the study by Myers et al.To clarify the respective roles of exercise capacity and heart rate, measured either at rest or after exercise, Myers et al. should reanalyze their data, taking into account this easily measurable variable.
Abstract 2671: CYP2D6 polymorphisms are not associated with tamoxifen outcome in premenopausal women with ER positive breast cancer of the POSH cohort
Authors: Pilar H. Saladores, Werner Schroth, Diana Eccles, William Tapper, Sue Gerty, Hiltrud B. Brauch
Journal: Cancer Research (2012)

Abstract Long-term adjuvant tamoxifen therapy for five years is the anti-estrogenic standard of care for ER-positive breast cancer in premenopausal patients. The metabolic activation of tamoxifen into the active metabolite endoxifen is mediated by Cytochrome P450 (CYP) 2D6 and it has been shown that CYP2D6 polymorphims can influence the clinical outcome of postmenopausal breast cancer patients (Schroth et al. JAMA 2009, Mürdter et al.CPT 2011). While this is currently still under debate awaiting the denouement (Brauch et al. JCO 2011), no such relationship has been investigated for premenopausal patients. We used the Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer (POSH) collection to explore the pharmacogenetic relationship between CYP2D6 polymorphisms and tamoxifen outcome in premenopausal patients. POSH is an observational cohort study established to explore the effect of genetic factors on breast cancer prognosis (Eccles et al. BMC Cancer 2007). We genotyped genomic DNA of 772 patients with adjuvant tamoxifen (age 18 to 41 years) for CYP2D6 and other CYP enzymes by MALDI TOF-MS. Patients were assigned for CYP2D6 metabolizer status, poor (PM), intermediate (IM), and extensive (EM), and tested for clinical associations using Kaplan-Meier and Cox regression analyses. After a median follow-up of 4 years (0.1 - 8 years) with 24.6% of study participants reporting a relapse, Kaplan Meier survival analysis did not show an association between CYP2D6 metabolizer status and the occurrence of relapse. In contrast, CYP3A5 functional status predicted by the *1 genotype was associated with worse outcome compared to the CYP3A5 deficient status (*3). Since chemotherapy is a suggested confounder of the CYP2D6 tamoxifen pharmacogenetic effect and the majority of POSH patients had received chemotherapy prior to tamoxifen, there is a possibility that variation in the metabolism and cytotoxic effects of these agents may mask CYP2D6 dependent tamoxifen outcome. However, in premenopausal patients due to higher plasma estrogen concentrations, the inhibition of tumor ER signaling may likely depend on factors other than endoxifen formation. While this is currently being explored with respect to the underlying ER pharmacodynamic effects, the polymorphic CYP3A5, one of the major drug metabolizing enzymes, appears to be a candidate marker for the prognosis of premenopausal breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2671. doi:1538-7445.AM2012-2671
Abstract 5257: Expression and functional role of CXCR5 and CXCL13 in non-small cell lung carcinoma (NSCLC)
Authors: Rajesh Singh, Shailesh Singh, William E. Grizzle, James W. Lillard
Journal: Cancer Research (2011)

Abstract Lung cancer is the leading cause of cancer related deaths worldwide. Chemokines and their corresponding receptor have been shown to play important role in cancer progression including lung cancer. In this regard, chemokine receptor CXCR5 has been implicated in metastatic dissemination in different models of melanoma, breast and prostate cancer. In this study we have shown that CXCR5 is highly expressed by the lung cancer cell lines and non-small cell lung carcinomas (NSCLC) tissue. CXCL13, which is the only natural ligand for CXCR5 is also expressed within the tumor. Retrospective analysis of CXCR5 expression in 45 patients specimens showed significantly higher expression of CXCR5 in Squamous cell carcinoma and Adenocarcinoma. Interestingly, nuclei of tumor cells were also positive for CXCR5 in more than 50% cases. Furthermore, serum analysis showed significantly higher serum levels of soluble CXCL13 in patients with Adenocarcinoma and Squamous cell carcinoma (n=31) compared to normal controls (n=9). The mechanism underlying these clinically and biologically important finding need to be further explored. Increased serum CXCL13 in lung cancer patients with metastatic disease required further validation as a potential therapeutic target and/or diagnostic marker for lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5257. doi:10.1158/1538-7445.AM2011-5257
Use of a Shared Medical Record With Secure Messaging by Older Patients With Diabetes
Authors: William G. Weppner, James D. Ralston, Thomas D. Koepsell, Lou C. Grothaus, Robert J. Reid, Luesa Jordan, Eric B. Larson
Journal: Diabetes Care (2010)

Evaluate use of a web-based shared medical record (SMR) between older patients with diabetes and providers.This was a retrospective cohort study. Health records and SMR use patterns of 6,185 enrollees aged ≥65 years with diabetes were analyzed from implementation of a SMR in August 2003 through December 2007. We analyzed baseline predictors of age, sex, distance from clinic, socioeconomic status, insulin use, morbidity, and associated primary care provider's (PCP) secure messaging use on patients' initial and subsequent use of the SMR. Changes in morbidity, PCP, or diabetes treatment were evaluated for impact on outcomes.A total of 32.2% of enrollees used the SMR; median rate was 1.02 user-days/month. Numbers of users and rate of use continued to increase. In adjusted analyses, likelihood of SMR use was associated with younger age, male sex, and higher socioeconomic status neighborhood, as well as clinical characteristics of overall morbidity and assigned PCP's use of secure messaging. Initial SMR use was more likely within 3 months of an increase in morbidity (hazard ratio 1.61, 95% CI 1.28-2.01) and within 1 month of changing to a PCP with higher use (3.02, 1.66-5.51).Four years after implementation, one-third of older individuals with diabetes had used the web-based SMR. Higher morbidity predicted initial and continued use of SMR services. Providers' use of the communication feature was associated with higher likelihood of SMR engagement by their patients. Web-based SMRs may be an effective form of non-visit-based health care for older individuals with diabetes.
Accidents to old people in their homes.
Authors: J. Agate
Journal: BMJ (1966)

Among young people the morbidity and mortality attributable to traffic accidents is already reaching disturbing proportions, but various kinds of accidents to older people are no less serious a medico-social problem of the times.A society like our own, with a large and still-increasing proportion of the elderly, must do everything possible to reduce the high accident rate among them because, humanitarian considerations apart, it throws a disproportionate strain upon medical, surgical, orthopaedic, and social services.
Fluconazole in the treatment of candidal prosthetic valve endocarditis.
Authors: B. J. Isalska, T. N. Stanbridge
Journal: BMJ (1988)

Although the suicide rate was high among men who had reported using narcotics more than 50 times, this variable was not a significant predictor in the Cox analysis, probably because few conscripts reported such heavy use.Yet the highest suicide rate (30/1000) was found among men who reported intravenous drug use.Similarly, alcohol use was associated with a high risk of suicide only among heavy drinkers-that is, those who drank spirits several times a week (table I).In several recent articles the possibility of predicting suicide in patients with psychiatric illness has been discussed.2224Pokorny concluded from a prospective study of 4800 such patients that the low sensitivity and specificity of risk factors and the low base rate of suicide made it impossible to predict suicide in individual cases.22Motto et al took a more optimistic view and developed a clinical instrument to estimate the risk of suicide based on a follow up of 2753 patients with psychiatric disease, although they pointed out its limitations.23Prediction of suicide in individual cases is even less feasible in an unselected population of conscripts as the base rate of suicide is much lower than that among patients with psychiatric illness.2423Thus our findings cannot be used to create an instrument to screen men at conscription.Preventing suicide in individual cases is most effec- tive in settings in which the associated risk factors are frequent.Thus people at risk tend to be seen by the social services, in treatment programmes for substance abuse, and in delinquency units.Knowledge of the predictors of suicide within these units may facilitate identification of those at risk and intervention.Future research should focus on markers of antisocial traits conducive to suicide in young men.