tbuckley/cabot-search huggingface dataset:
Nesidioblastosis Associated with Insulin-mediated Hypoglycemia in an Adult
Authors: David M Nathan, Lloyd Axelrod, Karl H Proppe, Robert Wald, Harry J Hirsch, Donald B Martin
Journal: Diabetes Care (1981)

Nesidioblastosis, the process of differentiation of pancreatic islets from ductular epithelium, is a well-described cause of insulin-mediated hypoglycemia in neonates and infants, but not in adults. A 58-yr-old woman with characteristic clinical features of fasting hypoglycemia had inappropriately elevated plasma immunoreactive insulin levels during symptomatic episodes of fasting hypoglycemia. Angiography, palpation at laparotomy, and resection of the distal three-quarters of the pancreas provided no evidence of a tumor. Pathologic examination of the resected pancreas revealed the findings of nesidioblastosis, i.e., budding of islets from the wall of ductules, and also increased number and size of islets and abnormal shape and location of islets. An entire spectrum of islet cell abnormalities including nesidioblastosis can cause insulin-mediated hypoglycemia in adults, as it does in neonates and infants.
CARCINOMA OF THE COLON
Authors: H. B. Devine
Journal: BMJ (1935)

limbs; osteogenesis imperfecta, etc.Of these we know little or nothing.That there is an urge to form.bone after its species pattern has been beautifully demonstrated by Dr. Honor Fell, and by the moving picture, by Canti, of her chick bones growing in vitro from the merest speck of tissue into the form and semblance of a femur without any stress or pull of muscle.When we know how that end is attained we shall be able to understand better the pathology of osseous and most other tissues.
?2-Macroglobulin is mainly produced by cancer cells and not by hepatocytes in rats with colon carcinoma metastases in liver
Authors: S M Smorenburg, P Griffini, A Tiggelman, A F Moorman, W Boers, C J Van Noorden
Journal: Hepatology (1996)

Localization and production of alpha2-macroglobulin (alpha2M), a multifunctional binding protein with protease and cytokine scavenging properties, was studied in situ in rat livers containing experimentally induced colon carcinoma metastases by means of immunocytochemistry and in situ hybridization methods. The study was performed to investigate whether alpha2M production by hepatocytes plays a role in the defense against the growth of metastases on the basis of its protease inhibiting capacity. It was found that colon cancer cells in all developmental stages of the metastases contained large amounts of messenger RNA (mRNA) of alpha2M but hardly any alpha2M protein. Cancer cells in culture contained large amounts of both mRNA and protein of alpha2M. In contrast, stromal cells and liver cells did not show positivity for alpha2M mRNA above background levels. The exception was a few layers of hepatocytes around the latest stage of metastases. Hepatocytes contained both alpha2M mRNA and protein only when Kupffer cells were present, indicating that alpha2M mRNA production was induced via Kupffer cells. On the other hand, alpha2M protein was found in high amounts in the sinusoids and stroma of all metastases, irrespective of their developmental stage. Increased levels of alpha2M could not be detected in serum in all but one rat tested (n=8). It is concluded that production of alpha2M by hepatocytes occurs only around the latest developmental stage of metastases and that alpha2M does not play a significant role in the defense against metastatic cancer growth in rat liver. In contrast, cancer cells produce and secrete large amounts of alpha2M, which seems to be linked with their tumorigenicity. We suggest that this alpha2M captures cytokines rather than proteases by complex formation. These complexes were observed using immunocytochemical staining for alpha2M protein indicating that it was captured by either stromal cells, sinusoidal cells, or hepatocytes that are in direct contact with cancer cells, Therefore, changes in serum levels of alpha2M were limited, indicating that these levels do not reflect local production and effects of alpha2M.
Evacuation of Subungual Haematoma
Authors: R. D. Willcock
Journal: BMJ (1952)

<h3>Introduction:</h3> Many practitioners routinely treat infants whose mean arterial blood pressure in mm Hg is less than their gestational age in weeks (GA). <h3>Objective:</h3> To assess the effectiveness of utilising a combined approach of clinical signs, metabolic acidosis and absolute blood pressure (BP) values when deciding to treat hypotension in the extremely low birthweight (ELBW) infant. <h3>Methods:</h3> Retrospective cohort study of all live born ELBW infants admitted to our neonatal intensive care unit over a 4-year period. Patients were grouped as either normotensive (BP never less than GA), hypotensive and not treated (BP&lt;GA but signs of good perfusion; we termed this permissive hypotension) and hypotensive treated (BP&lt;GA with signs of poor perfusion). <h3>Results:</h3> 118 patients were admitted during this period. Blood pressure data were available on 108 patients. 53% of patients were hypotensive (mean BP in mm Hg less than GA in weeks). Treated patients had lower birth weight and GA, and significantly lower blood pressure at 6, 12, 18 and 24 h. Normotensive patients and patients designated as having permissive hypotension had similar outcomes. Mean blood pressure in the permissive group increased from 26 mm Hg at 6 h to 31 mm Hg at 24 h. In a logistic regression model, treated hypotension is independently associated with mortality, odds ratio 8.0 (95% CI 2.3 to 28, p&lt;0.001). <h3>Conclusions:</h3> Blood pressure spontaneously improves in ELBW infants during the first 24 h. Infants hypotensive on GA criteria but with clinical evidence of good perfusion had as good an outcome as normotensive patients. Treated low blood pressure was associated with adverse outcome.
Chemokines induce matrix metalloproteinase-2 through activation of epidermal growth factor receptor in arterial smooth muscle cells
Authors: R KODALI, M HAJJOU, A BERMAN, M BANSAL, S ZHANG, J PAN, A SCHECTER
Journal: Cardiovascular Research (2005)

Objective: Matrix metalloproteinases (MMP) are critical to smooth muscle cell (SMC) migration in vivo. MMP-2 dysregulation has been implicated in the pathogenesis of abnormal arterial remodeling, aneurysm formation, and atherosclerotic plaque structure and stability. The chemokine receptors CCR3 and CXCR4 are present and functional on SMC and are up-regulated in vascular diseases such as atherosclerosis. We sought to determine a potential mechanism for chemokine receptor-mediated effects on the vasculature by asking whether the chemokines eotaxin (CCL11), the ligand for CCR3, and stromal cell-derived cell factor (SDF-1, CXCL12), the ligand for CXCR4, induce MMP-2 in SMC. Studies were then performed to define the signaling pathways involved.
PD10-01: Prevalence of Dysfunctional Fanconi Anemia (FA) DNA Repair Pathway in Breast Cancer.
Authors: B Ramaswamy, V Srividya, DA Mullins, S Carothers, G Young, D Wenrui, W Zhao, M Lustberg, M Leon, R Weslowski, R Layman, E Mrozek, CL Shapiro, M Villalona-Calero
Journal: Cancer Research (2011)

Abstract Purpose: BRCA1/2 deficient breast tumors are highly sensitive to poly- ADP-ribose polymerase inhibitors (PARPi). The Fanconi Anemia (FA) associated gene products along with BRCA 1/2 function in a common pathway that regulates the cellular response to DNA damage, suggesting that tumors with dysfunction of any of the components of FA network would be susceptible to PARPi. Understanding the prevalence of such defects in breast tumors using reproducible methodology will help us target these tumors with novel agents and potentially improve outcomes. Hence we sought to assess the prevalence of FA pathway defect in breast tumors by the absence of nuclear FANCD2 (a pivotal protein in the FA/BRCA pathway which is monoubiquitylated in the nucleus in response to DNA damage) repair foci using a novel immunofluorescence method and correlate this with known molecular markers of breast cancer. Methods: Using primary tumors obtained from the ongoing PARPi clinical trials (NCT01017640 and NCT01251874) and tumor bank, we evaluated 102 breast tumors for the somatic functionality of the FA pathway (FANCD2 foci formation) by the FA Triple Stain Immuno-Fluorescence (FATSI) test performed in a CLIA-certified laboratory using paraffin embedded tissues. The tissue sections are incubated with a primary antibody cocktail of rabbit polyclonal FANCD2 antibody and a monoclonal anti-Ki67 mouse antibody, followed by co-incubation with a secondary antibody (FITC conjugated to anti-rabbit IgG and Alexafluor 594 donkey anti-mouse), mounted on glass slides in a DAPI containing embedding medium and evaluated by a fluorescence microscope. Absence of nuclear FANCD2 formation in 100 proliferating tumor cells was considered positive for FA defect. Hormone receptor (HR) and Her2 status was compared between the groups using Fisher's exact test. Results: A total of 102 primary breast tumors were analyzed for FANCD2 by FATSI test of which 62 were triple negative (TN), 37 were HR positive and 3 were Her2 positive. Of these, 29 tumors (28%) were positive for FA defect with no significant differences among the molecular subtypes (26% in TN vs 32% in HR + vs 33% in Her2+). Conclusions: We report a novel methodology to efficiently screen archival FFPE tumors for somatic functional defect of FA DNA repair pathway and demonstrated a high prevalence (one-third) in breast tumors irrespective of molecular subtype. We are currently conducting clinical trials with PARPi including patients with tumors that test positive for FA defect to demonstrate if such tumors are sensitive to PARPi. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD10-01.
Treatment with cyclosporin and risks of graft rejection in male kidney and heart transplant recipients with non-O blood.
Authors: G. F. Hendriks, E. P. van Steenberge, G. M. Schreuder, G. J. Wenting, B. Mochtar, E. Bos, M. L. Simoons, A. H. Balk, K. Laird-Meeter, C. E. Essed
Journal: BMJ (1988)

In a consecutive series of 146 kidney transplant recipients treated with cyclosporin A a strong correlation between matching for the HLA-A, HLA-B, and HLA-DR loci specificities and outcome of the grafts was observed in male recipients with non-O blood groups. Such a beneficial effect of matching was not found in female patients or male patients with blood group O. In these patients survival of the grafts at one year was good irrespective of the number of HLA-A, B, and DR mismatches. Also in 47 male heart transplant recipients immune responsiveness against mismatched HLA antigens was related to blood group. A significantly higher incidence of rejection episodes was observed in male patients with non-O blood groups (n = 32) than in those with blood group O (n = 15). Matching for HLA-DR reduced the number of acute rejection episodes in male patients with non-O blood. These findings may help explain the controversial reports about the importance of HLA matching in organ transplantation. Furthermore, as most candidates for heart transplantation are male and not of blood group O, the higher incidence of graft rejection in these patients underscores the need for an exchange strategy of donor hearts.
Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Thalidomide Plus Dexamethasone Compared With Dexamethasone As Initial Therapy for Newly Diagnosed Multiple Myeloma
Authors: S. Vincent Rajkumar, Laura Rosiñol, Mohamad Hussein, John Catalano, Wieslaw Jedrzejczak, Lela Lucy, Marta Olesnyckyj, Zhinuan Yu, Robert Knight, Jerome B. Zeldis, Joan Bladé
Journal: Journal of Clinical Oncology (2008)

The long-term impact of thalidomide plus dexamethasone (thal/dex) as primary therapy for newly diagnosed multiple myeloma (MM) is unknown. The goal of this study was to compare thalidomide plus dexamethasone versus placebo plus dexamethasone (placebo/dex)as primary therapy for newly diagnosed MM.In this double-blind, placebo-controlled trial, patients with untreated symptomatic MM were randomized to thal/dex (arm A) or to placebo plus dexamethasone (dex) (arm B). Patients in arm A received oral thalidomide 50 mg daily, escalated to 100 mg on day 15, and to 200 mg from day 1 of cycle 2 (28-day cycles). Oral dex 40 mg was administered on days 1 through 4, 9 through 12, and 17 through 20 during cycles 1 through 4 and on days 1 through 4 only from cycle 5 onwards. Patients in arm B received placebo and dex, administered as in arm A. The primary end point of the study was time to progression. This study is registered at http://ClinicalTrials.gov (NCT00057564).A total of 470 patients were enrolled (235 randomly assigned to thal/dex and 235 to placebo/dex). The overall response rate was significantly higher with thal/dex compared with placebo/dex (63% v 46%), P < .001. Time to progression (TTP) was significantly longer with thal/dex compared with placebo/dex (median, 22.6 v 6.5 months, P < .001). Grade 4 adverse events were more frequent with thal/dex than with placebo/dex (30.3% v 22.8%).Thal/dex results in significantly higher response rates and significantly prolongs TTP compared with dexamethasone alone in patients with newly diagnosed MM.
Favorable results of debulking followed by immediate adjunct stent therapy for high risk saphenous vein graft lesions
Authors: Mun K. Hong, S.Chiu Wong, Jeffrey J. Popma, Lowell F. Satler, Kenneth M. Kent, Augusto D. Pichard, Gary S. Mintz, Theresa Bucher, Alan J. Merritt, J.Hope Pacera, Martin B. Leon
Journal: Journal of the American College of Cardiology (1996)
Stem Cell Response to Spatially and Temporally Displayed and Reversible Surface Topography
Authors: Murat Guvendiren, Jason A. Burdick
Journal: Advanced Healthcare Materials (2012)

The dynamic alignment of cells and matrix is critical in many biological processes, including during tissue development and in the progression of a variety of diseases; yet, nearly all in vitro models are static. Thus, it is of great interest to temporally and spatially manipulate cellular alignment to better understand and develop strategies to control these biological processes. Here, strain-responsive buckling patterns on PDMS substrates are used to dynamically and spatially control human mesenchymal stem cell (hMSC) organization. The results indicate that cellular alignment and pattern recognition are strongly diminished with culture time, which can be overcome by limiting cellular proliferation. Preferential alignment of the hMSCs is completely eliminated after the topography switch from patterned to flat, and can be reversibly repeated for at least 8 cycles. The hMSCs are responsive to dynamic changes in pattern size, where the distribution of the cells with preferential alignment increase with increasing pattern amplitude and decreasing wavelength. Furthermore, by introducing a biaxial stretching system, dynamic control is introduced over the cellular orientation angle and order, and by controlling the UV-ozone exposure of the PDMS, the topographical features can be spatially patterned.
New approaches to immunotoxicity testing.
Authors: D L Archer
Journal: Environmental Health Perspectives (1982)

New approaches to immunotoxicity testing are reviewed and discussed. A method of activating T-cells in vivo is presented which circumvents artifacts dur to viability effects encountered with in vitro mitogen assays. The use of adoptive transfer approaches to combine the advantages of in vitro manipulation with in vivo function assays is discussed relative to natural killer cells. The need for an in vitro metabolic activation step coupled to other in vitro immunologic assays is discussed.
Delayed Epiphyseal Closure in a Patient With β-Thalassemia Major Complicated by Hypogonadotrophic Hypogonadism
Authors: Quyen H. Nguyen, Michael Lin, Peter Lin, Nicholas Pocock
Journal: Clinical Nuclear Medicine (2007)

A 25-year-old man was referred for a bone scan to assess sacral pain on a background of β-thalassemia major complicated by severe anemia. He required repeated blood transfusions resulting in iron overload, which was treated with long-term iron chelation therapy. This case illustrates the potential skeletal manifestations of thalassemia and its treatment as demonstrated on bone scintigraphy, which include alterations in skeletal development and maturation, particularly delayed epiphyseal closure as well as complications of severe osteoporosis. Although the causes are multifactorial, pituitary iron deposition complicated by hypogonadotrophic hypogonadism should be considered as these patients may benefit from hormone replacement.
Chemotherapy-Induced Thrombocytopenia Derives from the Selective Death of Megakaryocyte Progenitors and Can Be Rescued by Stem Cell Factor
Authors: Ann Zeuner, Michele Signore, Daniela Martinetti, Monica Bartucci, Cesare Peschle, Ruggero De Maria
Journal: Cancer Research (2007)

Abstract Thrombocytopenia is a common side effect of chemotherapy, responsible for increased risk of bleeding and delay of treatment schedules in cancer patients. It is currently unknown how chemotherapeutic agents affect platelet production and whether the platelet precursors megakaryocytes represent a direct target of cytotoxic drugs. We investigated the effects of chemotherapeutic agents on primary megakaryocytes by using a culture system that recapitulates in vitro human megakaryopoiesis and found that cytotoxic drugs predominantly destroyed megakaryocytic progenitors at early stages of differentiation. Immature megakaryocytes could be protected from chemotherapeutic agents by the cytokine stem cell factor (SCF), which binds the c-kit receptor expressed on hematopoietic stem and progenitor cells. In chemotherapy-treated megakaryocytes, SCF activated Akt, neutralized the mitochondrial apoptotic machinery, and inhibited caspase activity. Interfering with Akt activation abrogated the antiapoptotic effects of SCF, whereas exogenous expression of constitutively active Akt inhibited drug-induced apoptosis of primary megakaryocytes, indicating the Akt pathway as primarily responsible for SCF-mediated protection of megakaryocyte progenitors. These results indicate apoptosis of megakaryocyte progenitors as a major cause of chemotherapy-induced thrombocytopenia and suggest that SCF may be used to prevent platelet loss in cancer patients with c-kit–negative tumors. [Cancer Res 2007;67(10):4767–4773]
Fibergastroscopy and Extragastric Lesions
Authors: G. Clémençon
Journal: Endoscopy (1972)

In 26 cases among 1000 fibergastroscopies an extragastric process was suspected. 17 of these cases were verified by either laparotomy or necropsy. The protrusion of the posterior gastric wall was a very indicative sign suggesting extragastric tumors. The lesions producing displacement of the gastric wall were pancreatic carcinoma, pancreatic cyst, chronic pancreatitis, retro-gastric lymph node metastases and aneurysma of the aorta. The importance of the endoscopic signs and the technique of this diagnostic approach are described and emphasized.
Photoscopy (Skiascopy or Retinoscopy).
Authors: Mark Delimon Stevenson, Mark D. Stevenson
Journal: JAMA (1907)

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 A18: The role of histone demethylase JARID1C in tumorigenesis of clear cell renal cell carcinoma
Authors: Lian Dee Ler, George Edward Allen, Swe Swe Myint, Bin Tean Teh
Journal: Cancer Research (2013)

Abstract Clear cell renal cell carcinoma (ccRCC) constitutes 75% of all RCC. It is characterized by inactivation of the tumor suppressor Von Hippel Lindau gene (VHL) in ~70% of sporadic ccRCC cases. Recent large scale screen of ~3,500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX, JARID1C and SETD2. These genes encode enzymes that demethylate and methylate key lysine residue of histone H3. In particular, JARID1C is a histone 3 lysine 4 (H3K4) demethylase involved in the demethylation of gene activating trimethyl H3K4 (H3K4me3) mark and was found to be mutated in 3-9% of ccRCC, independent of the mutation status of VHL. Using gene expression profiling, we revealed that major down-regulated pathways in primary RCCs harboring JARID1C inactivating mutation are pointing towards changes involving metastatic properties. The highlighted pathways include ECM-receptor interaction, focal adhesion, regulation of actin cytoskeleton, cell junction organization and cell junction assembly. Therefore, we focused on elucidating the role of JARID1C in ccRCC invasive properties. From in vitro assay, depletion of JARID1C by introducing JARID1C shRNA in ccRCC cells did not result in significant changes in cell migration. By contrast, in consistent with the findings from gene expression profiling, we showed that such depletion of JARID1C significantly enhances the invasiveness of ccRCC cells regardless of their VHL gene status. In summary, our findings establish the role of JARID1C in potentiating the invasive capabilities of ccRCC. Citation Format: Lian Dee Ler, George Edward Allen, Swe Swe Myint, Bin Tean Teh. The role of histone demethylase JARID1C in tumorigenesis of clear cell renal cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A18.