tbuckley/cabot-search huggingface dataset:
Continuous infusion indicator dilution measurement of limb blood flow and vascular response to magnesium sulfate in normotensive and hypertensive men
Authors: Henry W. Overbeck, Robert M. Daugherty, Francis J. Haddy
Journal: Journal of Clinical Investigation (1969)

A constant infusion, indicator dilution technique for blood flow measurements in the forearm and hand of man was tested and validated in vitro and in vivo. This technique employs jet injection to improve mixing of indicator with arterial blood. The mixing characteristics of the jet injection system were studied in vitro in tubing simulating the brachial artery of man. In addition, actual blood flows in the isolated pump-perfused forelimbs of five dogs were compared with constant infusion, indicator dilution calculated flows. Measurements were also made of mixing and of blood flow in the forearm and hand of man. The technique was used to compare forearm and hand vascular responses with constant intrabrachial arterial infusions of magnesium sulfate in 13 normotensive and 13 essential hypertensive men. In vitro and in vivo the jet injection system significantly improved mixing of indicator with blood, as compared with mixing produced by standard infusion techniques, without causing hemolysis. In 30 measurements in isolated, perfused dog forelimbs the correlation coefficient between actual and calculated blood flow was 0.992. Resting limb vascular resistance in the hypertensive group was significantly higher than in the normotensive group. Limb vascular resistance in all 26 men decreased in response to intrabrachial-arterial infusion of 0.25% magnesium sulfate (8 ml/min). Rate of infusion of Mg(++) was 0.162 mEq/min. There was a significant positive linear correlation between level of initial limb vascular resistance and magnitude of response to magnesium sulfate. Vascular response data adjusted for this source of variation were similar in hypertensives and normotensives.The data suggest that this constant infusion, indicator dilution technique allows accurate calculation of total limb blood flow in man, provided that anomalous bifurcation of the brachial artery is not present. The data also suggest that the jet injection system improves mixing of substances with arterial blood. Thus, use of this system should especially aid reliability of studies of limb vascular responses to vasoactive agents infused into the brachial artery.
Adoptive transfer of allotype-specific suppressor cells inhibits thymus-independent immunoglobulin production in syngeneic athymic mice.
Authors: E B Jacobson
Journal: The Journal of Experimental Medicine (1978)

(SJL X BALB)F1 suppressed mice have, in their lymphoid tissues, a population of suppressor T cells directed specifically against a paternal gamma G2a allotype (Ig-1b). Spleen or lymph node cells from these mice were injected into syngeneic nude mice and the effect on thymus-independent synthesis of Ig-1b in the athymic recipients was determined. After the injection of suppressor cells, Ig-1b disappeared from the serum of the recipients in a time course similar to that seen in normal mice. These results indicate that suppression occurs in the absence of thymus-derived helper cells, and they suggest that Ig-1b-producing B cells are the target of allotype-suppressor cells.
Mr 40,000 human colonic epithelial protein expression in colonic mucosa and presence of circulating anti-Mr 40,000 antibodies in cotton top tamarins with spontaneous colitis.
Authors: K M Das, M Vecchi, L Squillante, A Dasgupta, M Henke, N Clapp
Journal: Gut (1992)

Saguinus oedipus, Callithrix jacchus, and Saguinus fuscicollis are three species of New World monkeys which develop a form of colitis that is similar to human ulcerative colitis. Only S oedipus, however, develop colon cancer. We examined intestinal tissues from these animals for the presence of an antigen cross reacting to the Mr 40,000 human colonic epithelial protein that acts as an autoantigen in ulcerative colitis. Using an anti-Mr 40,000 monoclonal antibody (7E12H12, IgM isotype), by an immunoperoxidase assay we showed that all colon specimens from S oedipus reacted with 7E12H12; however, the colonic tissue from C jacchus and S fuscicollis did not. In immunotransblot analysis eluted IgG antibody bound to human ulcerative colitis colon (CCA-IgG) reacted with Mr 40,000 protein(s) present in the extracts of colon from S oedipus animals and humans. Small intestinal tissue reacted neither with 7E12H12 nor with CCA-IgG. In S oedipus, the Mr 40,000 protein was localised exclusively to colonic epithelial cells. Preincubation of seven S oedipus colon specimens with eight of 10 sera from animals with acute or chronic colitis and 0 of four sera from animals without colitis almost completely inhibited the binding of 7E12H12 to the colonic epithelium. Four of these 10 sera inhibited the binding of 7E12H12 to the autologous colon. These results show the presence of circulating autoantibodies in S oedipus with colitis against an epitope(s) on Mr 40,000 protein shared by human and S oedipus colon.
Stem Cell Therapies Benefit Alport Syndrome
Authors: Valerie LeBleu, Hikaru Sugimoto, Thomas M. Mundel, Behzad Gerami-Naini, Elizabeth Finan, Caroline A. Miller, Vincent H. Gattone, Lingge Lu, Charles F. Shield, Judah Folkman, Raghu Kalluri
Journal: Journal of the American Society of Nephrology (2009)

Patients with Alport syndrome progressively lose renal function as a result of defective type IV collagen in their glomerular basement membrane. In mice lacking the alpha3 chain of type IV collagen (Col4A3 knockout mice), a model for Alport syndrome, transplantation of wild-type bone marrow repairs the renal disease. It is unknown whether cell-based therapies that do not require transplantation have similar potential. Here, infusion of wild-type bone marrow-derived cells into unconditioned, nonirradiated Col4A3 knockout mice during the late stage of disease significantly improved renal histology and function. Furthermore, transfusion of unfractionated wild-type blood into unconditioned, nonirradiated Col4A3 knockout mice improved the renal phenotype and significantly improved survival. Injection of mouse and human embryonic stem cells into Col4A3 knockout mice produced similar results. Regardless of treatment modality, the improvement in the architecture of the glomerular basement membrane is associated with de novo expression of the alpha3(IV) chain. These data provide further support for testing cell-based therapies for Alport syndrome.
T<scp>HE</scp> R<scp>OLE OF</scp> C/EBP <scp>IN</scp> N<scp>UTRIENT AND</scp> H<scp>ORMONAL</scp> R<scp>EGULATION OF</scp> G<scp>ENE</scp> E<scp>XPRESSION</scp>
Authors: William J Roesler
Journal: Annual Review of Nutrition (2001)

C/EBPs are a family of transcription factors that play important roles in energy metabolism. Although initially thought to be constitutive regulators of transcription, an increasing amount of evidence indicates that their transactivating capacity within the cell can be modulated by nutrients and hormones. There are several mechanisms whereby this occurs. First, hormones/nutrients are known to directly alter the expression of C/EBPs. Second, hormones/nutrients may cause an alteration in the phosphorylation state of C/EBPs, which can affect their DNA-binding activity or transactivating capacity. Third, C/EBPs can function as accessory factors on gene promoters within a hormone response unit, interacting with other transcription factors to enhance the degree of responsiveness to specific hormones. Given their role in regulating genes involved in a wide variety of metabolic events, advancing our understanding of the molecular mechanism of action of C/EBPs will undoubtedly further our appreciation for the role these transcription factors play in both health and disease.
Notch signaling in stomach epithelial stem cell homeostasis
Authors: Tae-Hee Kim, Ramesh A. Shivdasani
Journal: The Journal of Experimental Medicine (2011)

The mammalian adult gastric epithelium self-renews continually through the activity of stem cells located in the isthmus of individual gland units. Mechanisms facilitating stomach stem and progenitor cell homeostasis are unknown. Here, we show that Notch signaling occurs in the mouse stomach epithelium during development and becomes restricted mainly to the isthmus in adult glands, akin to its known localization in the proliferative compartment of intestinal villi. Using genetic and chemical inhibition, we demonstrate that Notch signaling is required to maintain the gastric stem cell compartment. Activation of Notch signaling in lineage-committed stomach epithelial cells is sufficient to induce dedifferentiation into stem and/or multipotential progenitors that populate the mucosa with all major cell types. Prolonged Notch activation within dedifferentiated parietal cells eventually enhances cell proliferation and induces adenomas that show focal Wnt signaling. In contrast, Notch activation within native antral stomach stem cells does not affect cell proliferation. These results establish a role for Notch activity in the foregut and highlight the importance of cellular context in gastric tumorigenesis.
Israel allows sex selection of embryos for non-medical reasons
Authors: Judy Siegel Itzkovich
Journal: BMJ (2005)

Israeli parents who have at least four children of the same sex and want one of the other sex can now apply to a health ministry committee for approval of preimplantation genetic diagnosis at their own expense.

Professor Avi Yisraeli, director general of the health ministry, who issued the directive on the recommendation of experts on bioethics, said the new seven member body would approve sex selection of embryos for social reasons only in very unusual cases.

Except for one case officially approved …
Toxicologic Aspects of Occupational Hazards
Authors: Herbert E. Stokinger
Journal: Annual Review of Medicine (1956)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Effects of immunotherapy with a purified standardized allergen preparation of <i>Dermatophagoides farinae</i> in adults with perennial allergic rhinoconjunctivitis
Authors: T. Löfkvist, B. Agrell, S. Dreborg, G. Svensson
Journal: Allergy (1994)

Immunotherapy (IT) was performed for 12 months with a purified and standardized preparation of Dermatophagoides farinae. Twenty adults with rhinoconjunctivitis sensitive to house‐dust mite were given IT, and a similar group of 11 patients served as open controls. A total of 512 injections were given. Twenty‐eight episodes of allergic side‐effects occurred, 13 general and 15 local, most of them during the initial incremental dose period. No severe reactions started later than 30 min after the injection. One patient suffered anaphylactic shock. In this patient, specific antibodies fell immediately, followed by an increase within 1 week. The therapy group improved significantly in relation to the open controls in patients’ subjective evaluation of symptoms ( P &lt;0.028) and skin ( P &lt;0.0001) and conjunctival ( P &lt;0.001) sensitivity. Specific IgE increased in controls ( P &lt;0.0001) but not in IT‐treated patients during the “mite season;” that is, there was a significant difference in change during the observation period ( P &lt;0.0001). There was also a difference in change of specific IgG between the groups during the first 4–5 months and the whole year ( P &lt;0.0001), but not from 4–5 months to 12 months. In contrast to changes in antibody titers (IgG, P =0.04), changes in conjunctival ( P &lt;0.01) and especially skin sensitivity ( P &lt;0.005) correlated well with subjective improvement. This implies that the skin prick test and the conjunctival test can be recommended for follow‐up of IT. Furthermore, we recommend that changes in skin sensitivity be expressed as change in allergen concentration either inducing the same wheal response before and after IT as evaluated by parallel‐line bioassay, or inducing the same wheal response before and after IT as that induced by histamine tested at the same time. Finally, our findings support the hypothesis of a switch from IgE + to IgE ‐ during successful IT.
Management of Infections in the Neutropenic Patient
Authors: Kenneth V.I. Rolston
Journal: Annual Review of Medicine (2004)

Neutropenic patients continue to be at increased risk for developing serious infections despite substantial advances in supportive care. Epidemiologic shifts occur periodically and need to be detected early because they influence prophylactic, empiric, and specific therapy strategies. Although effective in preventing bacterial and some fungal infections, prophylaxis must be used with caution because it is associated with the emergence of resistance. The choices for empiric therapy include combination regimens and monotherapy. Specific choices depend on local factors (epidemiology, susceptibility/resistance patterns, availability). Various treatment settings (hospital-based, early discharge, outpatient) are also available, and the choice depends on the patient's risk category. Early diagnosis and treatment of many fungal and viral infections remains suboptimal. Infection control and prevention are important strategies, especially with the emergence of multidrug-resistant organisms.
Synthetic peptides from the circumsporozoite proteins of Plasmodium falciparum and Plasmodium knowlesi recognize the human hepatoma cell line HepG2-A16 in vitro.
Authors: S B Aley, M D Bates, J P Tam, M R Hollingdale
Journal: The Journal of Experimental Medicine (1986)

Several lines of evidence have emphasized the importance of the malaria circumsporozoite (CS) protein as a factor in sporozoite invasion of the hepatocyte; however, the specific mechanism of cell recognition and invasion has not been explained. In this study we present evidence that a highly conserved region of the CS protein immediately adjacent to the repeat region, the N1 region, specifically recognizes receptors on the human hepatoma cell line HepG2-A16 under conditions where invasion by sporozoites can occur. Peptides consisting of sequences from the repeat region or of the more extensive N2 region showed no such specific association. Antibody against the N1 peptide could inhibit sporozoite invasion in vitro. Covalent coupling of radiolabeled N1 peptide to HepG2-A16 cells identified two hepatic cell proteins to be closely associated with the peptide. We suggest that these proteins could act as receptors or mediators, via the N1 region of the CS protein, for the P. falciparum sporozoite in the process of invasion of the hepatocyte.
Intra-individual comparison of 18F-FET and 18F-DOPA in PET imaging of recurrent brain tumors
Authors: Clemens Kratochwil, Stephanie E. Combs, Karin Leotta, Ali Afshar-Oromieh, Stefan Rieken, Jürgen Debus, Uwe Haberkorn, Frederik L. Giesel
Journal: Neuro-Oncology (2013)

Both 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-fluoroethyltyrosine (18F-FET) have already been used successfully for imaging of brain tumors. The aim of this study was to evaluate differences between these 2 promising tracers to determine the consequences for imaging protocols and the interpretation of findings. Forty minutes of dynamic PET imaging were performed on 2 consecutive days with both 18F-DOPA and 18F-FET in patients with recurrent low-grade astrocytoma (n = 8) or high-grade glioblastoma (n = 8). Time-activity-curves (TACs), standardized uptake values (SUVs) and compartment modeling of both tracers were analyzed, respectively. The TAC of DOPA-PET peaked at 8 minutes p.i. with SUV 5.23 in high-grade gliomas and 10 minutes p.i. with SUV 4.92 in low-grade gliomas. FET-PET peaked at 9 minutes p.i. with SUV 3.17 in high-grade gliomas and 40 minutes p.i. with SUV 3.24 in low-grade gliomas. Neglecting the specific uptake of DOPA into the striatum, the tumor-to-brain and tumor-to-blood ratios were higher for DOPA-PET. Kinetic modeling demonstrated a high flow constant k1 (mL/ccm/min), representing cellular internalization through AS-transporters, for DOPA in both high-grade (k1 = 0.59) and low-grade (k1 = 0.55) tumors, while lower absolute values and a relevant dependency from tumor-grading (high-grade k1 = 0.43; low-grade k1 = 0.33) were observed with FET. DOPA-PET demonstrates superior contrast ratios for lesions outside the striatum, but SUVs do not correlate with grading. FET-PET can provide additional information on tumor grading and benefits from lower striatal uptake but presents lower contrast ratios and requires prolonged imaging if histology is not available in advance due to a more variable time-to-peak.
Hsa-miR-31-3p Expression Is Linked to Progression-free Survival in Patients with KRAS Wild-type Metastatic Colorectal Cancer Treated with Anti-EGFR Therapy
Authors: Gilles Manceau, Sandrine Imbeaud, Raphaële Thiébaut, François Liébaert, Karine Fontaine, Francis Rousseau, Bérengère Génin, Delphine Le Corre, Audrey Didelot, Marc Vincent, Jean-Baptiste Bachet, Benoist Chibaudel, Olivier Bouché, Bruno Landi, Frédéric Bibeau, Karen Leroy, Frédérique Penault-Llorca, Jean-Luc Van Laethem, Pieter Demetter, Sabine Tejpar, Simona Rossi, Neda Mosakhani, Pia Österlund, Raija Ristamäki, Virinder Sarhadi, Sakari Knuutila, Valérie Boige, Thierry André, Pierre Laurent-Puig
Journal: Clinical Cancer Research (2014)

To identify microRNAs (miRNA) that predict response to anti-EGFR antibodies in patients with wild-type KRAS metastatic colorectal cancer (mCRC).miRNA profiling was performed in a training set of 87 patients with mCRC refractory to chemotherapy treated with anti-EGFR antibodies. This included 33 fresh-frozen (FF) and 35 formalin-fixed paraffin-embedded (FFPE) samples retrospectively collected and 19 prospectively collected FF samples. An independent validation cohort consisting of 19 FF and 26 FFPE prospectively collected samples from patients with mCRC treated with anti-EGFR antibodies was used to confirm our findings.After screening the expression of 1,145 miRNAs in FF samples from the training set, we identified that hsa-miR-31-3p expression level was significantly associated with progression-free survival (PFS). Statistical models based on miRNA expression discriminated between high and low risk of progression for both FF and FFPE samples. These models were confirmed in the validation cohort for both FF [HR, 4.1; 95% confidence interval (CI), 1.1-15.3; P < 0.04] and FFPE samples (HR, 2.44; 95% CI, 1.1-5.4; P = 0.028). The percentage of variation of RECIST criteria in the validation series was significantly associated with the expression level of hsa-miR-31-3p (r(2) = 0.49; P = 0.0035) and risk status determined by hsa-miR-31-3p expression level (P = 0.02, Kruskal-Wallis rank test). Nomograms were built and validated to predict PFS-depending on hsa-miR-31-3p expression level. Following in vitro studies, we identified 47 genes regulated by hsa-miR-31-3p.Hsa-miR-31-3p seems to be a new mCRC biomarker whose expression level allows for the identification of patients with wild-type KRAS mCRC who are more likely to respond to anti-EGFR therapy.
Anti-Epithelial Cell Adhesion Molecule Antibodies and the Detection of Circulating Normal-Like Breast Tumor Cells
Authors: Anieta M. Sieuwerts, Jaco Kraan, Joan Bolt, Petra van der Spoel, Fons Elstrodt, Mieke Schutte, John W. M. Martens, Jan-Willem Gratama, Stefan Sleijfer, John A. Foekens
Journal: JNCI Journal of the National Cancer Institute (2008)

Identification of specific subtypes of circulating tumor cells in peripheral blood of cancer patients can provide information about the biology of metastasis and improve patient management. However, to be effective, the method used to identify circulating tumor cells must detect all tumor cell types. We investigated whether the five subtypes of human breast cancer cells that have been defined by global gene expression profiling—normal-like, basal, HER2-positive, and luminal A and B—were identified by CellSearch, a US Food and Drug Administration–approved test that uses antibodies against the cell surface–expressed epithelial cell adhesion molecule (EpCAM) to isolate circulating tumor cells. We used global gene expression profiling to determine the subtypes of a well-defined panel of 34 human breast cancer cell lines (15 luminal, nine normal-like, five basal-like, and five Her2-positive). We mixed 50-150 cells from 10 of these cell lines with 7.5 mL of blood from a single healthy human donor, and the mixtures were subjected to the CellSearch test to isolate the breast cancer cells. We found that the CellSearch isolation method, which uses EpCAM on the surface of circulating tumor cells for cell isolation, did not recognize, in particular, normal-like breast cancer cells, which in general have aggressive features. New tests that include antibodies that specifically recognize normal-like breast tumor cells but not cells of hematopoietic origin are needed.
Identification of an interleukin (IL)-25–dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion
Authors: Padraic G. Fallon, Sarah J. Ballantyne, Niamh E. Mangan, Jillian L. Barlow, Ayan Dasvarma, Duncan R. Hewett, Ann McIlgorm, Helen E. Jolin, Andrew N.J. McKenzie
Journal: The Journal of Experimental Medicine (2006)

Type 2 immunity, which involves coordinated regulation of innate and adaptive immune responses, can protect against helminth parasite infection, but may lead to allergy and asthma after inappropriate activation. We demonstrate that il25−/− mice display inefficient Nippostrongylus brasiliensis expulsion and delayed cytokine production by T helper 2 cells. We further establish a key role for interleukin (IL)-25 in regulating a novel population of IL-4–, IL-5–, IL-13–producing non–B/non–T (NBNT), c-kit+, FcεR1− cells during helminth infection. A deficit in this population in il25−/− mice correlates with inefficient N. brasiliensis expulsion. In contrast, administration of recombinant IL-25 in vivo induces the appearance of NBNT, c-kit+, FcεR1− cells and leads to rapid worm expulsion that is T and B cell independent, but type 2 cytokine dependent. We demonstrate that these IL-25–regulated cells appear rapidly in the draining lymph nodes, implicating them as a source of type 2 cytokines during initiation of worm expulsion.
A Specific Stimulator of Granulocyte Colony-Stimulating Factor Accelerates Recovery From Cyclophosphamide-Induced Neutropenia in the Mouse
Authors: Jay S. Fine, Xiao-Yan Cai, Luminita Justice, Carl P. Gommoll, Linda D. Hamilton, Tracey A. Waters, Satwant K. Narula, Loretta A. Bober, Michael J. Grace
Journal: Blood (1997)
SEASONAL VARIATION IN THE INCIDENCE OF SEVERELY CRIPPLING MENTAL DISORDERS
Authors: NELSON J. BRADLEY, RUBEL J. LUCERO
Journal: American Journal of Psychiatry (1958)

Some characteristics of 976 consecutive admissions to the Willmar State Hospital over a period of 3 years were studied in terms of their variability within months and seasons of the year. Various facts leading to hypotheses emerged from the study. The reservation was stated that the results of the study apply specifically to rural areas. The study must be replicated in an urban hospital to conclude anything about urban areas.