tbuckley/cabot-search huggingface dataset:
Gene expression pattern in hepatic stem/progenitor cells during rat fetal development using complementary DNA microarrays
Authors: Petko M. Petkov, Jiri Zavadil, David Goetz, Tearina Chu, Robert Carver, Charles E. Rogler, Erwin P. Bottinger, David A. Shafritz, Mariana D. Dabeva
Journal: Hepatology (2004)

To identify new and differentially expressed genes in rat fetal liver epithelial stem/progenitor cells during their proliferation, lineage commitment, and differentiation, we used a high throughput method-mouse complementary DNA (cDNA) microarrays-for analysis of gene expression. The gene expression pattern of rat hepatic cells was studied during their differentiation in vivo: from embryonic day (ED) 13 until adulthood. The differentially regulated genes were grouped into two clusters: a cluster of up-regulated genes comprised of 281 clones and a cluster of down-regulated genes comprised of 230 members. The expression of the latter increased abruptly between ED 16 and ED 17. Many of the overexpressed genes from the first cluster fall into distinct, differentially expressed functional groups: genes related to development, morphogenesis, and differentiation; calcium- and phospholipid-binding proteins and signal transducers; and cell adhesion, migration, and matrix proteins. Several other functional groups of genes that are initially down-regulated, then increase during development, also emerged: genes related to inflammation, blood coagulation, detoxification, serum proteins, amino acids, lipids, and carbohydrate metabolism. Twenty-eight genes overexpressed in fetal liver that were not detected in adult liver are suggested as potential markers for identification of liver progenitor cells. In conclusion, our data show that the gene expression program of fetal hepatoblasts differs profoundly from that of adult hepatocytes and that it is regulated in a specific manner with a major switch at ED 16 to 17, marking a dramatic change in the gene expression program during the transition of fetal liver progenitor cells from an undifferentiated to a differentiated state. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Immunotherapy of Malignant Melanoma.
Authors: M. Mastrangelo
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Immunotherapy of Malignant Melanoma.M. Mastrangelo, M.D., R. S. Bornstein, M.D., H. Sulit, M.D., D. Chee, Ph.D., J. VV. Yarbro, M.D., F.A.C.P., R. T. Prehn, M.D.M. Mastrangelo, M.D.Search for more papers by this author, R. S. Bornstein, M.D.Search for more papers by this author, H. Sulit, M.D.Search for more papers by this author, D. Chee, Ph.D.Search for more papers by this author, J. VV. Yarbro, M.D., F.A.C.P.Search for more papers by this author, R. T. Prehn, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-877_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptExtensive investigation of the immunology of animal and human neoplasia suggests that host immunity may be a significant factor in host resistance to cancer. Furthermore, this immunological response may be capable of augmentation. The frequency of spontaneous regressions and the often noted occurrence of metastatic disease many years after removal of the primary lesion have suggested that host factors may play a role in the control of human melanoma. The lack of efficacy of conventional means of therapy has lent impetus to an immunological approach to the treatment of inoperable melanoma. Several uncontrolled studies utilizing intralesional injection of BCG vaccine... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byBCG in der Immuntherapie von Tumoren — Eine kurze historische ÜbersichtLocal immunotherapy — Experimental and clinical researchBCG and Cancer 1 May 1972Volume 76, Issue 5Page: 877-878KeywordsBacille calmette guerinCancer immunotherapyImmunityImmunologyLesionsMelanomaVaccines Issue Published: 1 May 1972 PDF downloadLoading ...
The renal cGMP-gated cation channel: Its molecular structure and physiological role
Authors: David E. McCoy, Sandra E. Guggino, Bruce A. Stanton
Journal: Kidney International (1995)

Cyclic nucleotide-gated cation channels, which are permeable to monovalent and divalent cations, are expressed in a number of tissues. cDNAs encoding cGMP-gated cation channel subunits have been cloned in retinal rods, cones, olfactory neuroepithelium, pineal gland, aorta, testis, heart, and most recently kidney. Patch clamp studies have identified and characterized cGMP-gated cation channels in the cortical collecting duct (CCD) and inner medullary collecting duct (IMCD). cGMP-gated cation channels in kidney share many biophysical and molecular properties with the retinal rod cGMP-gated channel. However, unlike the retinal rod channel, the cGMP-gated cation channel in kidney is inhibited by cGMP and stimulated by increased calcium levels. In the IMCD the cGMP-gated cation channel mediates electrogenic sodium absorption which is inhibited by ANP via cGMP. Recently, cGMP-gated cation channel poly(A+) RNA has been identified in other nephron segments by RT-PCR and in situ PCR hybridization. Furthermore, cGMP-gated cation channel protein has also been identified in all nephron segments by Western blot analysis. These observations suggest that cGMP-gated cation channels, or closely related gene products, may play an important physiological role in all nephron segments. Hormones that increase intracellular cGMP may regulate sodium, and perhaps calcium, uptake in nephron segments proximal to the IMCD. Increases in cell sodium and calcium may regulate other transport and signaling pathways.
QUALITY OF LIFE 60 DAYS AFTER AN ACUTE HEART FAILURE EVENT: INSIGHTS FROM THE PROTECT TRIAL
Authors: John Cleland, Karen Chiswell, Gerasimos Filippatos, Michael Givertz, Barry Massie, Gad Cotter, Beth Davison, Mona Fiuzat, A.A. Voors, George Mansoor, Piotr Ponikowski, John Teerlink, Christopher O&apos;Connor
Journal: Journal of the American College of Cardiology (2012)
Abstract PR2: Stroma-derived matrix metalloproteinase 9 (MMP9) confers resistance to anti-EGFR therapy through cell-extrinsic activation of ERBB2/ERK/JUN pathway
Authors: Janghee Woo, Morikawa Teppei, Shuji Ogino, Ramesh A. Shivdasani
Journal: Clinical Cancer Research (2012)

Abstract Matrix metalloproteinases (MMPs) have been studied historically for their role in tissue invasion and metastasis. The tumor microenvironment also produces MMPs that may influence other tumor behaviors, as recent mouse models suggest in the intestine and other sites. We examined MMP9 expression in 642 cases of human colorectal cancer (CRC) in relation to clinicopathological features and mutations. MMP9 antibody (Ab) unambiguously stained mesenchymal cells in 104 cases (16.2%) and gave weaker stromal staining in another 12.8%. High stromal MMP9 expression correlated most strongly with the CpG island methylator phenotype (CIMP-high) in tumors (multivariate odds ratio – OR – 2.45, 95% confidence interval – CI – 1.41 to 4.27, p=0.0015) and also with absence of tumor KRAS mutations (multivariate OR 0.54, 95% CI 0.33 to 0.87, p=0.011). The latter association suggested KRAS allelic status as one reason for heterogeneity in CRC cell line responses to MMP9. Four out of 6 KRASWT cell lines proliferated significantly more in the presence of exogenous MMP9, while 4 of 5 KRASMut lines failed to respond. This led us to ask if stromal MMP9 expression might predict the outcome of treatment with anti-EGFR mAb cetuximab, allowing KRASWT tumors to bypass mAb blockade of EGFR-KRAS pathway activation. We retrospectively evaluated MMP9 expression by immunohistochemistry on primary tumors and progression-free survival (PFS) in 86 patients who had received chemotherapy combined with cetuximab as first-line or salvage therapy. Tumors from 29 patients (33.8%) harbored mutant KRAS. PFS of patients with MMP9high;KRASWT tumors (median 3.5 months) was lower than that of patients with low or no stromal MMP9 expression and KRASWT tumors (median 5.8 months, 95% CI for the hazard ratio 1.135-2.179). Patients with KRASMut tumors showed no significant difference in PFS with respect to MMP9 expression (2.55 months and 2.25 months in the MMP9high and MMP9neg/low subgroups, respectively). Thus, low stromal MMP9 expression in KRASWT tumors predicted a better outcome with cetuximab treatment than high MMP9 expression. In CRC cell lines that grow faster in response to MMP9, this factor activates ERBB2 and ERK/JUN signaling. Together, these findings suggest that stroma-derived MMP9 may help tumors bypass common mutational mechanisms for constitutive growth factor pathway activation and confer resistance to anti-EGFR therapy through cell-extrinsic activation of the ERBB2/ERK/JUN pathway. Stromal MMP9 expression may thus predict cetuximab response in KRASWT CRCs and have value in selecting patients for treatment. This proffered talk is also presented as Poster A26.
Epidemic Poliomyelitis, Des Moines, Iowa, 1959
Authors: James F. Speers
Journal: JAMA (1960)

In 1959 a severe epidemic of type-1 poliomyelitis occurred in Des Moines and the surrounding area of Polk County, Iowa. Of the 178 cases reported between May 1 and Oct. 31, 74 were paralytic and 104 were nonparalytic. The epidemic was characterized by an early seasonal onset, with the highest incidence among unvaccinated preschool children of low-income families. The attack rate of the lower socioeconomic group was eight times higher than that of the upper socioeconomic group. The incidence of paralytic poliomyelitis was considerably lower in persons who had received three or more injections of Salk vaccine compared with that of the unvaccinated group.
Vasculitis: Eds G V Ball, S L Bridges, Jr. (Pp 601; pound110.) Oxford: Oxford University Press, 2002. ISBN 0-1926-3053-9.
Authors: A Wiik
Journal: Annals of the Rheumatic Diseases (2002)

Role of HLA genes in familial spondyloarthropathySaid-Nahal and colleagues report an intriguing finding of an association with HLA-DR4 independent of B27 in families with ankylosing spondylitis (AS), 1 a finding highlighted by an accompanying editorial. 2 The approach of studying B27 positive and B27 negative haplotypes may prove powerful in identifying further cis or trans encoded genes involved in AS.However, the reported association of DR4 with AS is quite a surprising finding given that no difference was noted in B27-DR4 haplotype frequencies in patients and ethnically matched healthy controls.Many previous studies have not reported any such association, 3-9 including a similar preliminary study by the same authors. 10Although these studies were mainly case-control studies, population stratification is highly unlikely to cause a false negative finding if the effect size of the reported association with DR4 is as high as Said-Nahal and colleagues describe.We are concerned that both the family and case-control results are biased by the statistical approach employed.Multicase families were used in the study, yet a form of transmission test for linkage disequilibrium (TDT) was used 11 which is only suitable for single affected families, and is a valid test only of linkage, and not of association, when applied to multicase families. 12Therefore the TDT p values reported in tables 5, 6, and 7 of Said-Nahal's paper 1 for the patients and unaffected B27+siblings do not reflect association alone, and will be affected by the strong linkage of the major histocompatibility complex with AS, and also probably by bias due to the different numbers of parent-case trios selected from different multicase families.Forms of TDT are available for general pedigree families and are more powerful than the TDT employed in this study (for example, see Clayton 13 ).These biases also apply to the case-control component of the study (results presented in tables 2, 3, and 4) where it appears that related cases were employed.If so, these results also reflect both linkage and association.We would be interested to see the results of a further analysis allowing for these considerations.
FDG-PET on the Trail of an Unsuspected Primary Malignancy in the Breast
Authors: Keith F. Dockery, Savita Puri, Raman Qazi, Delphine Davis
Journal: Clinical Nuclear Medicine (2008)

Proper identification of the primary malignancy can radically alter clinical management for the patient's benefit. This is a report of an unsuspected primary breast cancer in a patient being worked up for presumptive lymphoma. Prior investigation of lymphedema in the left lower extremity found widespread lymphadenopathy on computed tomography imaging, leading to initial biopsy revealing adenocarcinoma of unknown primary. F-18 fluorodeoxyglucose PET/computed tomography altered management by localizing an F-18 fluorodeoxyglucose avid breast nodule, directing breast biopsy with specific immunohistochemical analysis for breast cancer lineage in metastatic adenocarcinoma. The patient responded well to breast cancer-targeted chemotherapy.
Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock.
Authors: C Natanson, P W Eichenholz, R L Danner, P Q Eichacker, W D Hoffman, G C Kuo, S M Banks, T J MacVittie, J E Parrillo
Journal: The Journal of Experimental Medicine (1989)

Survivors of both human and animal bacterial shock develop a characteristic pattern of progressive changes in cardiovascular function over a period of 7-10 d. In this present study, we examined whether endotoxin (a product of Gram-negative bacteria) or TNF (a cytokine released from macrophages) could reproduce the same complex cardiovascular changes observed in septic shock over a period of 7-10 d. To test this hypothesis, we implanted a thrombin-fibrin clot containing purified endotoxin from E. coli into the peritoneal cavity of eight dogs, and infused TNF into eight different dogs. Over the next 10 d, serial simultaneous heart scans and thermodilution cardiac outputs were performed in these awake nonsedated animals. By day 2 after challenge with either endotoxin or TNF, animals developed a decrease (p less than 0.05) in both mean arterial pressure and left ventricular ejection fraction. With fluid resuscitation, animals manifested left ventricular dilatation (increased [p less than 0.05] end diastolic volume index), increased or normal cardiac index, and decreased or normal systemic vascular resistance index. In surviving animals, these changes returned to normal with 7-10 d. The time course of these changes was concordant (p less than 0.05) with that previously described in a canine model of septic shock using viable bacteria. During the 10-d study, control animals receiving sterile clots or heat-inactivated TNF had not significant changes in hemodynamics. The results from this canine model demonstrate that either endotoxin or TNF alone can produce many of the same hemodynamic abnormalities seen in human septic shock and in a canine septic shock model induced by live bacteria. These findings support the hypothesis that the action of endogenous mediators (TNF) responding to bacterial products (endotoxin) is the common pathway that produces the serial cardiovascular changes found in septic shock.
Evangelists and Snails
Authors: Frank Davidoff
Journal: Annals of Internal Medicine (1996)

Letters15 December 1996Evangelists and SnailsFrank Davidoff, MD, EditorFrank Davidoff, MD, EditorEditor.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-12-199612150-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dostoevsky reminded us that faith makes miracles, rather than the other way around. And while I agree with Dr. Sullivan that both judgment and faith enter substantially into the perspective of the cholesterol “evangelists,” it is only fair to point out that judgment and faith enter into the “snail” position as well. More generally, it is true that data by themselves, even the best data on a problem, are never enough to serve as the basis for medical action. To start with, physicians must find the problem interesting (important to them); then they need to believe in the ...References1. Davidoff F. Heart and head: feeling and thought in the teaching of medicine. In: Who Has Seen a Blood Sugar? Reflections on Medical Education. Philadelphia: American College of Physicians; 1996:152-7. Google Scholar2. Davidoff F. Evangelists and snails redux: the case of cholesterol screening [Editorial]. Ann Intern Med. 1996; 124:513-4. Google Scholar3. American College of Physicians. Guidelines for using serum cholesterol, high-density lipoprotein cholesterol, and triglyceride levels as screening tests for preventing coronary heart disease in adults. Ann Intern Med. 1996; 124:515-7. Google Scholar4. LaRosa JC. Cholesterol agonistics. Ann Intern Med. 1996; 124:505-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: Editor. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 1996Volume 125, Issue 12Page: 1012KeywordsCholesterolEmotions Issue Published: 15 December 1996 CopyrightCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
The ubiquitous presence of warts on human skin needs acknowledgement for better direction of papillomavirus research
Authors: C.G. Burkhart
Journal: British Journal of Dermatology (2005)

Conflicts of interest: none declared. Sir, The recent article by Adachi et al.1 reporting the detection of human papillomavirus (HPV) in hair follicles in the genital region of a woman appears to provide another example of the ubiquitous nature of the virus on the skin, mucous membranes and appendages. Indeed, it appears that if degenerate consensus polymerase chain reaction sets were available to amplify all of the HPV types known, this virus would be found almost universally to be a normal inhabitant of all epithelial tissues.2 How else can one explain the documented detection of HPV vaginally in prepubertal girls and in virgins without sexual exposure?3, 4 Moreover, the vertical transmission of the virus appears to occur at childbirth.5 It appears that endogenous, exogenous and latent infections with HPV exist.2 Indeed, two or more HPV types were detected in lesions clinically designated as warts.6 This new concept has repercussions regarding (i) the ease of developing vaccines, and (ii) treatments designed to eliminate the virus totally from the skin and mucous membranes. My research in this area is in trying to assist the body to reject the exogenous virus by reducing the tumour load of the HPV overgrowth. In my mind, the HPV in hair follicles referred to by Adachi et al.1 is merely a small portion of the vast reservoir of HPV on our human exterior.
THE SUPRARENAL CORTEX AND TUMOR
Authors: WILLIAM H. WOGLOM
Journal: JAMA (1930)

The possibility of a relationship between the suprarenal cortex and the growth of malignant neoplasms has recently become a prominent subject of inquiry. Sokoloff<sup>1</sup>has recorded the absorption of transplanted animal tumors after they had been injected with a preparation of cortex and an iron salt through which the gland was assumed to direct metabolism. Arloing, Josserand and Charachon<sup>2</sup>have described an inhibition of the growth of a mouse carcinoma after the subcutaneous introduction of suprarenal gland from a rabbit prepared by inoculations of the same tumor; they<sup>2</sup>found a glycerinated extract equally effective, whereas the normal gland proved to be inert, whether extracted or not. Activity was referred by these authors also to the cortex. Coffey and Humber,<sup>3</sup>finally, have said that an extract of suprarenal cortex from the sheep causes sloughing and ultimate disappearance of malignant tumors in man, but they regarded their investigation
Treatment of relapsed or refractory Hodgkin disease and non‐Hodgkin lymphoma with high‐dose chemoradiotherapy followed by unstimulated autologous peripheral stem cell rescue
Authors: Aaron P. Rapoport, Jacob M. Rowe, Joanna M. Heal, Martin A. Tanner, John F. Dipersio
Journal: American Journal of Hematology (1992)

Nine patients with relapsed or refractory Hodgkin disease or non-Hodgkin lymphoma underwent peripheral stem cell autografting because of a history of marrow involvement with visible lymphoma. Peripheral stem cells were collected during a process of unstimulated leukapheresis. Recovery to a neutrophil count of 0.1 x 10(9)/L was seen at a median of 14 days compared with a median of 18 days for a concurrent series of marrow recipients (P = .12). Recoveries to a neutrophil count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L occurred at medians of 25 days and 28 days, respectively. These figures are not significantly different from those obtained in the marrow recipients. Of the original nine patients, six are surviving free of disease progression or relapse at a median of 240 days posttransplant. Two patients died of transplant-related complications and one relapsed 250 days post-transplant. All surviving patients remain independent of transfusions and six have attained almost complete hematological reconstitution. Although administration of cytotoxic therapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance the yield of early progenitor cells during leukapheresis, unstimulated leukapheresis results in a stem cell product capable of rapidly restoring and sustaining marrow function even after multiple courses of intensive "salvage" therapy. Additional follow-up will be needed to determine whether preliminary survival figures continue to compare favorably with those of patients with similar extramedullary disease states undergoing marrow transplants.
Cancer of the Cervix
Authors: Philip Rubin
Journal: JAMA (1965)

It is estimated that 13,000 women die in this country each year of carcinoma of the cervix. 2 This cancer is exceeded only by cancer of the breast in women in regard to incidence, with a rate of 14 to 25 per 100,000 female population. In some of the underdeveloped countries, such as China and Mexico, over half of all cancers in the female arise in the uterine cervix. Age distribution is such that the highest rates are in the fifth and sixth decades of life. In the very young and in females under twenty, this is a rare lesion and, if present, most often is an adenocarcinoma.  Analysis of a variety of factors has led authors to conclude that cervicitis, obstetrical trauma, and lacerations have etiological implications in cancer of the cervix. The evidence suggesting an increase in cervical carcinoma in those females having coitus at an early age,
Dissecting Aneurysm of the Aorta with Renal Complications
Authors: H. Brebner
Journal: BMJ (1951)

INFANTMBRun adenocarcinoma of the cervix uteri, demonstrated by histological sections.The younger died of the disease on the day of admission, having had vaginal bleeding for about one month.The second was treated by total hysterectomy eight days after the onset of vaginal bleeding, and was reported well and developing normally 21 months after the operation.
Relief of pain by infusion of morphine after operation
Authors: M H Ornstein
Journal: BMJ (1985)

increased incidence of nausea and vomiting was during the first or second 24 hour period.In either casc higher peak blood morphine concentrations would have been experienced by the infusion group, so this finding is not unexpected.We feel that this study has given a false impression of the technique of continuous opiate analgesia.