tbuckley/cabot-search huggingface dataset:
Candidate Microbicides Block HIV-1 Infection of Human Immature Langerhans Cells within Epithelial Tissue Explants
Authors: Tatsuyoshi Kawamura, Sandra S. Cohen, Debra L. Borris, Elisabeth A. Aquilino, Svetlana Glushakova, Leonid B. Margolis, Jan M. Orenstein, Robin E. Offord, A. Robert Neurath, Andrew Blauvelt
Journal: The Journal of Experimental Medicine (2000)

Initial biologic events that underlie sexual transmission of HIV-1 are poorly understood. To model these events, we exposed human immature Langerhans cells (LCs) within epithelial tissue explants to two primary and two laboratory-adapted HIV-1 isolates. We detected HIV-1Ba-L infection in single LCs that spontaneously emigrated from explants by flow cytometry (median of infected LCs = 0.52%, range = 0.08–4.77%). HIV-1–infected LCs downregulated surface CD4 and CD83, whereas MHC class II, CD80, and CD86 were unchanged. For all HIV-1 strains tested, emigrated LCs were critical in establishing high levels of infection (0.1–1 μg HIV-1 p24 per milliliter) in cocultured autologous or allogeneic T cells. HIV-1Ba-L (an R5 HIV-1 strain) more efficiently infected LC–T cell cocultures when compared with HIV-1IIIB (an X4 HIV-1 strain). Interestingly, pretreatment of explants with either aminooxypentane-RANTES (regulated upon activation, normal T cell expressed and secreted) or cellulose acetate phthalate (potential microbicides) blocked HIV-1 infection of LCs and subsequent T cell infection in a dose-dependent manner. In summary, we document HIV-1 infection in single LCs after exposure to virus within epithelial tissue, demonstrate that relatively low numbers of these cells are capable of inducing high levels of infection in cocultured T cells, and provide a useful explant model for testing of agents designed to block sexual transmission of HIV-1.
THE RUNNING EAR
Authors: H. N. Barnett
Journal: BMJ (1929)

Of thwe gariiietit brings this article of underwear inito very intintate contact with those parts wlhere heat anid miioistuire re faoura<ble to fungus; growth.It is possible that the ]ew Shlirt twax have bornie the contagion intto the houlse;oIL thle other lianid, a fa.vic m iouse fIloom tlle household grLoup inay have contaminated it.This is mere conjecture, ior Ina1inn pos.s.ible wa.ys of infec-tioni sufggest themiselves.Apropos of tlis, I oInce treated tlhree bachtelortt br-other's foir tiiiea crurlis.The first, whose elider-mal scales micro- seopicnafly examihied shiowed the Epidcrm ioplhytoti injigmtale, lha(d tusve (a str.ange closet-of the earth vtariety, I believe- whien out sliooting.Dotubtless the otlhier twio lhad coii- tracted the disease fiom one of the water-closets in tlhei Counltrv holuse, commoin to them all.Tihe sctuttula were removed, and all the lesions cleared up with'ii a fortnlight unider salicylic acid and ammoniated rercury ointtmlenits of appropriate strength .It was found oeco>Sa mv to employ a boric aci(d andl calamineilotion (CCWSi&flmOIl,Y, after washing off the oiiitntent, owing to the >e'alSitiVless of the skin of the parts.'THE RUNNING EAR.
Low-dose continuous chemotherapy (LBCMVD-56) for refractory and relapsing lymphoma
Authors: J. Shamash, J. Walewski, J. Apostolidis, A.M. Wilson, J.M. Foran, R.K. Gupta, A.Z.S. Rohatiner, S.M. Kelsey, T.A. Lister
Journal: Annals of Oncology (2000)
THE DISTRICT BRANCH OF THE APA : ITS ORIGIN, PRESENT STATUS, AND FUTURE DEVELOPMENT
Authors: WALTER H. OBENAUF
Journal: American Journal of Psychiatry (1959)

This paper has represented an attempt to summarize the facts pertinent to the development and present status of the District Branch movement that is now progressing within the American Psychiatric Association. Some reflections concerning and suggestions about organization for the effective meeting of local and statewide needs for psychiatry have been offered. The related matter of adjustments between the District Branch and the Affiliated Society has also been discussed and the need for continued liaison with our medical brethren emphasized. It is this writer's earnest hope that he may have stimulated thinking on these matters in some small degree; that constructive and fruitful discussion may follow; that out of collective wisdom flowing from the democratic process, the American Psychiatric Association may continue to maintain an organizational structure that will permit the perpetuation of her status, not only as the oldest Medical Association of National size in North America, but also as the recognized leader in the fight against mental illness as well.
Fast Facts: Irritable Bowel Syndrome, 2nd edn
Authors: D Thompson
Journal: Gut (2004)

W Grant Thompson, K W Heaton. Oxford: Health Press, 2003, £12.00, pp 96. ISBN ISBN 1-903734-33-9

Functional gastrointestinal disorders in general, and irritable bowel syndrome in particular, have long been a minefield of misunderstanding and mismanagement which has caused confusion not only to clinicians but also to patients.

In recent years, an international working team have attempted to resolve this babel-like tower of confusion by forming the now famous Rome group and …
BMX Negatively Regulates BAK Function, Thereby Increasing Apoptotic Resistance to Chemotherapeutic Drugs
Authors: Joanna L. Fox, Alan Storey
Journal: Cancer Research (2015)

Abstract The ability of chemotherapeutic agents to induce apoptosis, predominantly via the mitochondrial (intrinsic) apoptotic pathway, is thought to be a major determinant of the sensitivity of a given cancer to treatment. Intrinsic apoptosis, regulated by the BCL2 family, integrates diverse apoptotic signals to determine cell death commitment and then activates the nodal effector protein BAK to initiate the apoptotic cascade. In this study, we identified the tyrosine kinase BMX as a direct negative regulator of BAK function. BMX associates with BAK in viable cells and is the first kinase to phosphorylate the key tyrosine residue needed to maintain BAK in an inactive conformation. Importantly, elevated BMX expression prevents BAK activation in tumor cells treated with chemotherapeutic agents and is associated with increased resistance to apoptosis and decreased patient survival. Accordingly, BMX expression was elevated in prostate, breast, and colon cancers compared with normal tissue, including in aggressive triple-negative breast cancers where BMX overexpression may be a novel biomarker. Furthermore, BMX silencing potentiated BAK activation, rendering tumor cells hypersensitive to otherwise sublethal doses of clinically relevant chemotherapeutic agents. Our finding that BMX directly inhibits a core component of the intrinsic apoptosis machinery opens opportunities to improve the efficacy of existing chemotherapy by potentiating BAK-driven cell death in cancer cells. Cancer Res; 75(7); 1345–55. ©2015 AACR.
A Chemical Screen Identifies Anisomycin as an Anoikis Sensitizer That Functions by Decreasing FLIP Protein Synthesis
Authors: Imtiaz A. Mawji, Craig D. Simpson, Marcela Gronda, Moyo A. Williams, Rose Hurren, Clare J. Henderson, Alessandro Datti, Jeffrey L. Wrana, Aaron D. Schimmer
Journal: Cancer Research (2007)

Abstract Malignant epithelial cells with metastatic potential resist apoptosis that normally occurs upon loss of anchorage from the extracellular matrix, a process termed “anoikis.” Resistance to anoikis enables malignant cells to survive in an anchorage-independent manner, which leads to the formation of distant metastases. To understand the regulation of anoikis, we designed, automated, and conducted a high-throughput chemical screen for anoikis sensitizers. PPC-1 anoikis–resistant prostate cancer cells were seeded in hydrogel-coated ultralow binding plates for suspension conditions and standard tissue culture plates to promote adhesion. After seeding, cells were treated with aliquots from a library of previously characterized small molecules, and viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt, assay. From this chemical screen, we identified anisomycin that induced apoptosis in suspension conditions, but was not toxic to these cells grown under adherent conditions. Anisomycin sensitized cells to anoikis by decreasing levels of the caspase-8 inhibitor FLIP and subsequently activating the death receptor pathway of caspase activation. Although anisomycin activated c-Jun-NH2-kinase and p38, these kinases were not functionally important for the effect of anisomycin on anoikis and FLIP. Rather, anisomycin decreased FLIP and sensitized cells to anoikis by inhibiting its protein synthesis. Finally, we showed that anisomycin decreased distal tumor formation in a mouse model of prostate cancer metastases. Thus, a novel chemical screen identified anisomycin as an anoikis sensitizer that acts by decreasing FLIP protein synthesis. Our results suggest that FLIP is a suppressor of anoikis and inhibiting FLIP protein synthesis may be a useful antimetastatic strategy. [Cancer Res 2007;67(17):8307–15]
An Innovative or Disconcerting Approach to the Psychosocial Care of Your Patient With a Cardiac Condition
Authors: Karina W. Davidson, Ian M. Kronish, Jonathan A. Shaffer
Journal: JAMA Internal Medicine (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Histogenesis of human colorectal adenomas and hyperplastic polyps: the role of cell proliferation and crypt fission
Authors: W-M Wong
Journal: Gut (2002)

Background: The histogenesis of human colorectal hyperplastic polyps and colorectal adenomas is poorly understood even now. Method: Human colorectal adenomas, hyperplastic polyps, and normal colorectal mucosae (patients with familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma were excluded) were obtained during colonoscopy and microdissected into individual crypts. Morphology, cell proliferation characteristics, and fission indices of crypts isolated from these lesions were then studied. Results: Crypts isolated from colorectal adenomas and colorectal hyperplastic polyps were significantly larger (p&lt;0.001) than crypts from normal colorectal mucosae. Crypt fission was an uncommon event in normal colonic mucosae but common in crypts isolated from adenomas and hyperplastic polyps (p&lt;0.001). Analysis of the distribution of mitoses suggested an upward expansion of the proliferation compartment in adenomas to the surface of the crypt with no reversal of proliferating cell distribution, as has previously been described. Conclusions: Sporadic human colorectal adenomas and hyperplastic polyps grow by the process of crypt fission. Expansion of the proliferative compartment was demonstrated in crypts from adenomas, consistent with deregulation of cell cycle control.
MicroRNA-494 Reduces ATF3 Expression and Promotes AKI
Authors: Yi-Fan Lan, Hsi-Hsien Chen, Pei-Fang Lai, Ching-Feng Cheng, Yen-Ta Huang, Yi-Chao Lee, Tzen-Wen Chen, Heng Lin
Journal: Journal of the American Society of Nephrology (2012)

MicroRNA-494 mediates apoptosis and necrosis in several types of cells, but its renal target and potential role in AKI are unknown. Here, we found that microRNA-494 binds to the 3'UTR of activating transcription factor 3 (ATF3) and decreases its transcription. In mice, overexpression of microRNA-494 significantly attenuated the level of ATF3 and induced inflammatory mediators, such as IL-6, monocyte chemotactic protein-1, and P-selectin, after renal ischemia/reperfusion, exacerbating apoptosis and further decreasing renal function. Activation of NF-κB mediated this proinflammatory response. In this ischemia/reperfusion model, urinary levels of microRNA-494 increased significantly before the rise in serum creatinine. In humans, urinary microRNA-494 levels were 60-fold higher in patients with AKI than normal controls. In conclusion, upregulation of microRNA-494 contributes to inflammatory or adhesion molecule-induced kidney injury after ischemia/reperfusion by inhibiting expression of ATF3. Furthermore, microRNA-494 may be a specific and noninvasive biomarker for AKI.
The Blood Vascular Supply of the Dental Pulp with Emphasis on Capillary Circulation
Authors: D. VINCENT PROVENZA
Journal: Circulation Research (1958)

Histologic study of the capillary bed contained within the pulps of human teeth shows components which differ as to the presence or absence of muscle in their walls. The vessels which supply the capillary network of the pulp are metarterioles and precapillaries with their sphincters. Arteriovenous anastomoses are also found in the pulp.
Precore wild-type DNA and immune complexes persist in chronic hepatitis B after seroconversion: No association between genome conversion and seroconversion
Authors: Toshiyuki Maruyama, Shoji Kuwata, Kazuhiko Koike, Shiro Iino, Kiyomi Yasuda, Hiroshi Yotsuyanagi, Kyoji Moriya, Hisato Maekawa, Haruki Yamada, Yoichi Shibata, David R. Milich
Journal: Hepatology (1998)

Precore hepatitis B virus (HBV) mutants may gradually prevail during or after seroconversion (SC) from hepatitis B e antigen (HBeAg) to hepatitis B e antigen antibody (anti-HBe) status in many chronic hepatitis B (CH-B) patients. However, patients with CH-B still produce anti-HBe more than several years after SC, and the relationship between SC and genome conversion in the precore region has not been clarified. Therefore, in patients with CH-B who had a sustained loss of HBeAg and complete remission of hepatitis after SC, the precore region was sequenced in paired serum samples from 1 year before SC to 3 years after SC. Mutant precore defective HBV DNA was found in only 6 (19%) of 31 CH-B patients who had a complete remission of hepatitis after SC. Mixed-type HBV DNA (precore wild-type and mutant-type) was found in 4 (13%) patients. Wild-type HBV DNA was found in 21 (68%) CH-B patients after SC. Longer-term follow-up of 11 CH-B patients indicated that 3 of 11 patients experienced precore genome conversion 2 to 3 years after SC. E-plus DNA or e-minus DNA was semiquantitated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays before and after SC. E-plus DNA levels decreased from 10 5.56±1.58 to 10 2.45±1.61 . Similarly, e-minus DNA levels declined from 10 4.25±1.56 to 10 1.86±1.37 . By dot-blot assay, serum HBV DNA became negative soon after SC, as did serum HBeAg. In contrast, HBeAg-containing immune complexes were still detected after SC. Anti-HBe antibody was produced throughout SC and thereafter, as determined by a sensitive experimental assay. Therefore, we conclude that genome-conversion in the precore region is a separate event from HBeAg/anti-HBe seroconversion.
Whole Genome Comparison of Allelic Imbalance between Noninvasive and Invasive Small-Sized Lung Adenocarcinomas
Authors: Hirofumi Nakanishi, Shingo Matsumoto, Reika Iwakawa, Takashi Kohno, Kenji Suzuki, Koji Tsuta, Yoshihiro Matsuno, Masayuki Noguchi, Eiji Shimizu, Jun Yokota
Journal: Cancer Research (2009)

Seventy-two small-sized (<or=2 cm in diameter) lung adenocarcinomas consisting of 15 noninvasive and 57 invasive tumors were subjected to whole genome allelic imbalance (AI) scanning and mutational analysis of the EGFR, KRAS, and TP53 genes to elucidate genetic pathways of early-stage lung adenocarcinomas. The chromosome 13q13 region showed the most frequent AI (58%) and was affected at similar frequencies between noninvasive and invasive tumors (53% and 60%, respectively), as EGFR and KRAS mutations were. The number of AI regions as well as the frequency of TP53 mutations in invasive tumors was significantly higher than those in noninvasive ones [9.8 +/- 5.6 versus 4.8 +/- 2.8 (P = 0.00002) and 61% versus 13% (P = 0.001), respectively]. In particular, AIs at the chromosome 11p11-p12, 17p12-p13, and 18p11 regions in invasive tumors were significantly more frequent than those in noninvasive ones (P < 0.01). The results indicated that noninvasive tumors were developed by EGFR, KRAS, and 13q alterations and progressed to invasive ones by subsequent alterations of several tumor suppressor genes, including those on 11p11-p12, 17p12-p13, and 18p11 and TP53. AI at 8p21 was significantly more frequent in advanced stages (>IA) and associated with worse prognoses (P = 0.04) and, thus, would be involved in invasion and/or metastasis of adenocarcinoma cells and useful for the prediction of prognosis of patients with small-sized lung adenocarcinoma.
Microbes and metabolic health
Authors: Fergus Shanahan
Journal: Gut (2012)

The global epidemic of obesity and obesity-associated disorders, including diabetes, metabolic syndrome and cardiovascular disease, continues apace despite widespread public health education. The problem is also set to emerge in regions undergoing socioeconomic development. The fact that obesity arises from a chronic surplus of energy consumption over energy expenditure is self-evident, but this is not the whole story. Effective preventive strategies need to look beyond simple calorific mathematics.

Among the more intriguing developments in medicine in recent years, the evidence linking indigenous microbiota with obesity and obesity-associated complications has been significant. This is a complex relationship. For example, a direct, obligate role for the microbiota in atherosclerosis has recently been identified with the discovery of a microbial-dependent pathway for metabolism of dietary phospholipids, which generates metabolites that are pro-atherosclerotic after absorption and hepatic metabolism.1 Even more intriguing is the microbial contribution to the metabolic processes underpinning obesity. This involves multi-directional signalling among the microbiota, host metabolism and immunity, with dietary intake influencing each component of this triangular network.2–4

Obesity is characterised by insulin resistance and a state of low-grade inflammation or metabo-inflammation.5 This differs in many respects from classical inflammation: it is induced by nutrient overload, is associated with reduced metabolic rate, is characterised …
Druggable Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma
Authors: Takashi Nakaoku, Koji Tsuta, Hitoshi Ichikawa, Kouya Shiraishi, Hiromi Sakamoto, Masato Enari, Koh Furuta, Yoko Shimada, Hideaki Ogiwara, Shun-ichi Watanabe, Hiroshi Nokihara, Kazuki Yasuda, Masaki Hiramoto, Takao Nammo, Teruhide Ishigame, Aaron J. Schetter, Hirokazu Okayama, Curtis C. Harris, Young Hak Kim, Michiaki Mishima, Jun Yokota, Teruhiko Yoshida, Takashi Kohno
Journal: Clinical Cancer Research (2014)

Abstract Purpose: To identify druggable oncogenic fusions in invasive mucinous adenocarcinoma (IMA) of the lung, a malignant type of lung adenocarcinoma in which KRAS mutations frequently occur. Experimental Design: From an IMA cohort of 90 cases, consisting of 56 cases (62%) with KRAS mutations and 34 cases without (38%), we conducted whole-transcriptome sequencing of 32 IMAs, including 27 cases without KRAS mutations. We used the sequencing data to identify gene fusions, and then performed functional analyses of the fusion gene products. Results: We identified oncogenic fusions that occurred mutually exclusively with KRAS mutations: CD74-NRG1, SLC3A2-NRG1, EZR-ERBB4, TRIM24-BRAF, and KIAA1468-RET. NRG1 fusions were present in 17.6% (6/34) of KRAS-negative IMAs. The CD74-NRG1 fusion activated HER2:HER3 signaling, whereas the EZR-ERBB4 and TRIM24-BRAF fusions constitutively activated the ERBB4 and BRAF kinases, respectively. Signaling pathway activation and fusion-induced anchorage-independent growth/tumorigenicity of NIH3T3 cells expressing these fusions were suppressed by tyrosine kinase inhibitors approved for clinical use. Conclusions: Oncogenic fusions act as driver mutations in IMAs without KRAS mutations, and thus represent promising therapeutic targets for the treatment of such IMAs. Clin Cancer Res; 20(12); 3087–93. ©2014 AACR.
Experimental systemic amyloidosis induced by immunization with syngeneic organ extracts in mice.
Authors: Y Mori, B Akikusa, T Mori, S Ueda, K Iesato, H Yoshida, M Ogawa, I Kato, Y Wakashin, M Wakashin
Journal: The Journal of Experimental Medicine (1986)

Systemic amyloidosis was induced consistently in mice by intramuscular injection of syngeneic organ (liver and kidney) extracts mixed with CFA six times at weekly intervals. Syngeneic organ extract with CFA also induced amyloidosis of a lesser degree. All three strains of mice (C57BL/6, C3H/He, and BALB/c) injected with a syngeneic liver extract mixed with CFA developed systemic amyloidosis; the most prominent amyloid deposition occurred in C57BL/6 (B6) mice, followed by C3H/He and BALB/c. The amyloid substance deposited in these animals was identified as mouse amyloid A protein (AA). Furthermore, an organ specificity of the immunogen in inducing amyloidosis was suggested with liver and kidney extracts. Primed spleen cells of the immunized B6 mice were fractionated by a nylon-wool column and injected to normal recipient mice via the tail vein. Organs of the recipient mice developed systemic amyloidosis 8 wk after the transfer, and the most prominent histological changes occurred in the recipient mice given nylon-wool column adherent spleen cells. Using anti-Thy-1,2; Ly-1; Ly-2, antibody and complement, it was suggested that T cells, especially Ly-1,2,3+ T cell populations in the primed nylon-wool adherent cells, play an important role in the induction of systemic amyloidosis. It was shown further that the amyloidosis-inducing substance in liver extract was composed of unstable proteins or protein-bound substance.
ALCAT1 controls mitochondrial etiology of fatty liver diseases, linking defective mitophagy to steatosis
Authors: Li Wang, Xiaolei Liu, Jia Nie, Jun Zhang, Scot R. Kimball, Hai Zhang, Weiping J. Zhang, Leonard S. Jefferson, Zeneng Cheng, Qiuhe Ji, Yuguang Shi
Journal: Hepatology (2014)

Defective autophagy is implicated in the pathogenesis of nonalcoholic fatty liver diseases (NAFLD) through poorly defined mechanisms. Cardiolipin is a mitochondrial phospholipid required for bioenergetics and mitophagy from yeast to mammals. Here we investigated a role for ALCAT1 in the development of NAFLD. ALCAT1 is a lysocardiolipin acyltransferase that catalyzes pathological cardiolipin remodeling in several aging-related diseases. We show that the onset of diet-induced NAFLD caused autophagic arrest in hepatocytes, leading to oxidative stress, mitochondrial dysfunction, and insulin resistance. In contrast, targeted deletion of ALCAT1 in mice prevented the onset of NAFLD. ALCAT1 deficiency also restored mitophagy, mitochondrial architecture, mitochondrial DNA (mtDNA) fidelity, and oxidative phosphorylation. In support of a causative role of the enzyme in a mitochondrial etiology of the disease, hepatic ALCAT1 expression was significantly up-regulated in mouse models of NAFLD.Forced expression of ALCAT1 in primary hepatocytes led to multiple defects that are highly reminiscent of NAFLD, including steatosis, defective autophagy, and mitochondrial dysfunction, linking pathological cardiolipin remodeling by ALCAT1 to the pathogenesis of NAFLD.