tbuckley/cabot-search huggingface dataset:
Abnormalities of Albumin Metabolism in Patients with Hypogammaglobulinemia.
Authors: T. A. Waldmann
Journal: Annals of Internal Medicine (1962)

s1 April 1962Abnormalities of Albumin Metabolism in Patients with Hypogammaglobulinemia.T. A. Waldmann, M.D., L. Laster, M.D.T. A. Waldmann, M.D.Search for more papers by this author, L. Laster, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-692_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe electrophoretic patterns of serum proteins of 20 patients with deficient synthesis of gamma globulin revealed that in 15 the serum albumin concentration was less than 3.5 g/100 ml, and in six of these it was under 2.5 g/100 ml. The hypoalbuminemia associated with hypogammaglobulinemia was investigated by using intravenously-injected albumin-radioactive iodine and polyvinylpyrrolidine (PVP)-radioactive iodine to assess albumin synthesis and enteric loss of albumin.Six patients with decreased serum and total body albumin were studied. Each had significant diarrhea and steatorrhea. In three, albumin synthesis was markedly impaired but a normal survival time of albumin-I131(disappearance rate, 18 to... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, Md. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByBasic Science Review : The Exudative Gastroenteropathies 1 April 1962Volume 56, Issue 4Page: 692-693KeywordsAlbuminsAttentionDiarrheaGlobulinsSerum albuminSerum proteins Issue Published: 1 April 1962 PDF DownloadLoading ...
A protein called OPN3 may play a role in skin ageing caused by sunlight
Authors: Y. Lan, Y. Wang, H. Lu
Journal: British Journal of Dermatology (2020)

Our skin is regularly exposed to UV radiation from the sun. Chronic, meaning long‐term, exposure to UV radiation (mainly a type of UV called UVA) causes an increase in enzymes called matrix metalloproteinases (MMPs), especially MMP1, MMP2, MMP3 and MMP9, in skin cells called human dermal fibroblasts (HDFs). MMPs can lead to the breakdown of fibrous connective tissue which gives the skin its support and structure, and this is the most important cause of skin photo‐aging (skin aging caused by UV). We don't exactly know how, on a molecular level, fibroblasts sense UVA and trigger signals via cells to MMPs. This study looked at a type of protein in the body called Opsins (OPNs) which can change their signaling pathways (how they communicate with other cells) in response to being hit by light. OPNs play a vital role in our sight, circadian rhythm (our sleep‐wake cycle) and how the eye's pupil responds to light. This study provides evidence that a type of OPNs called OPN3 plays a role in the production of MMP1, MMP2, MMP3 and MMP9 in HDFs following UVA exposure. This provide insights into the understanding of the molecular mechanisms through which human skin cells respond to UVA radiation, and may reveal molecular targets for preventing or treating skin photo‐ageing. This is a summary of the study: Opsin 3 is a key regulator of ultraviolet A‐induced photoageing in human dermal fibroblast cells.
Hiding in the Water
Authors: Dejan Micic, Aytekin Oto, Michael R. Charlton, Jean-Luc Benoit, Mark Siegler
Journal: New England Journal of Medicine (2020)

A 59-year-old woman presented with a 3-month history of dyspepsia and loss of appetite. Her upper abdominal discomfort was sharp in quality, radiated to the right upper quadrant, persisted for 3 to 5 hours, and occurred roughly every 6 days.
John Graham Dickinson
Authors: Mary Probyn (Harding)
Journal: BMJ (2020)

John Graham Dickinson was born in London and qualified in Oxford, where he met his wife, Angela. They married in 1963, and after working in London for a few years they moved in 1969 with their very young family to Kathmandu, Nepal, where he worked as a missionary doctor until 1986. During those years he worked at Shanta Bhawan Hospital as a consultant physician specialising in tuberculosis, was involved in pioneering work on altitude sickness (which included storing a yak heart and lungs in the family fridge to be sent abroad for further analysis of altitude adaptation in the yak, much to the disgust of …
Targeting oncogenic Eph receptor proteins with Hsp90 inhibitors
Authors: balasubramaniam annamalai, Xueguang Liu, Jacob Fraser, Jennifer Isaacs
Journal: Cancer Research (2007)

5629  Eph receptor tyrosine kinases (RTKs), with 16 distinct members, constitute the largest kinase family. The members of this superfamily regulate cellular boundaries, cell migration, and vascular morphogenesis. The Eph RTKs are highly promising targets in a wide variety of cancers, due to their selective overexpression and activation in tumors. Eph RTKs are subdivided into 2 families (EphA and EphB), based on their sequence homologies and ligand-binding specificities. EphA2 and several EphB family members have emerged as pivotal players in angiogenesis, invasion, and tumorigenic progression and are correlated with a highly invasive phenotype. Eph RTKs associate with their ligands, the ephrins, which are normally found on the cell surface of opposing cells. Cell contact promotes ligand binding, which triggers phosphorylation of the C-terminal kinase domain and transmittance of cellular signaling cascades. Ligand binding has a tumor-inhibitory role for EphA2, resulting receptor internalization and protein downregulation mediated by a proteasome-dependent pathway. In cancer cells, dysregulated cell-cell contact translates to diminished receptor-ligand assocation, resulting in overexpression of active receptor. Many oncogenic RTKs interact with heat shock protein 90 (Hsp90), a molecular chaperone involved in mediating the proper conformation and function of a multitude of signaling proteins. We report here that the Eph RTKs examined in this study, EphA2 and EphB1, form a complex with Hsp90 and co-chaperones. This association is mediated by the kinase domain of the receptor, as deletions of this domain abrogate both Hsp90 binding and sensitivity to drug. This is a significant finding, as Hsp90 inhibitors, such as the clinically-utilized 17-AAG, mediate the proteasome-dependent downregulation of Hsp90 substrates, or ‘client’ proteins. Moreover, we demonstrate that Hsp90 inhibiting agents efficiently diminish the levels of Eph receptor. These data demonstrate that Hsp90 plays an essential role in eph RTK function and may contribute to the anti-angiogenic and anti-migratory properties of 17-AAG. Furthermore, this finding suggests that Hsp90 inhibitors may be exploited as a novel means to downregulate the selective overexpression of these receptors in cancers.
Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19
Authors: Maximilian F Konig, Alfred HJ Kim, Marc H Scheetz, Elizabeth R Graef, Jean W Liew, Julia Simard, Pedro M Machado, Milena Gianfrancesco, Jinoos Yazdany, Daman Langguth, Philip C Robinson
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Background:</h3> Advanced laparoscopic training is becoming a valuable asset for surgeons as more procedures are carried out in a minimally invasive fashion. The purpose of our study was to determine whether laparoscopic fellowship training affects outcomes in patients undergoing laparoscopic cholecystectomy for acute cholecystitis. <h3>Methods:</h3> We obtained data from a retrospective review of 110 patients with acute cholecystitis who underwent laparoscopic cholecystectomy on an urgent basis from March 2002 to June 2005. We compared the outcomes of 31 patients whose surgeries were performed by a surgeon with advanced laparoscopic training with those of 79 patients whose surgeries were performed by surgeons without such training. <h3>Results:</h3> The 2 groups were similar in terms of demographics and time to surgery. Outcome measures included conversion rates, postoperative length of stay (LOS) and complications. There was a significant difference in conversion rates (3.2 % v. 16.5 %, <i>p</i> = 0.050) and postoperative LOS (1.77 v. 2.82 d, <i>p</i> &lt; 0.006) between the 2 groups, but there was no difference in the rate of postoperative complications. There was no significant difference in conversion rates among the surgeons without advanced training (<i>p</i> = 0.64). <h3>Conclusion:</h3> Based on our results, laparoscopic cholecystectomy in acute cholecystitis is associated with improved outcomes when performed by a surgeon with fellowship training in laparoscopic surgery.
Late-onset “acute fibrinous and organising pneumonia” impairs long-term lung allograft function and survival
Authors: Arno Vanstapel, Stijn E. Verleden, Birgit Weynand, Eric Verbeken, Laurens De Sadeleer, Bart M. Vanaudenaerde, Geert M. Verleden, Robin Vos
Journal: European Respiratory Journal (2020)

Acute fibrinous and organising pneumonia (AFOP) after lung transplantation is associated with a rapid decline in pulmonary function. However, the relation with chronic lung allograft dysfunction (CLAD) remains unclear. We investigated the association between detection of AFOP in lung allograft biopsies with clinically important endpoints. We reviewed lung allograft biopsies from 468 patients who underwent lung transplantation at the University Hospitals Leuven (2011–2017). AFOP was categorised as early new-onset (≤90 days post-transplant) or late new-onset (&gt;90 days post-transplant); and associated with CLAD-free survival, graft survival, donor-specific antibodies, airway and blood eosinophilia. Early and late AFOP was detected in 24 (5%) and 30 (6%) patients, respectively. CLAD-free survival was significantly lower in patients with late AFOP (median survival 2.42 years; p&lt;0.0001) compared with patients with early or without AFOP and specifically associated with development of restrictive allograft syndrome (OR 28.57, 95% CI 11.34–67.88; p&lt;0.0001). Similarly, graft survival was significantly lower in patients with late AFOP (median survival 4.39 years; p&lt;0.0001) compared with patients with early AFOP or without AFOP. Late AFOP was furthermore associated with detection of circulating donor-specific antibodies (OR 4.75, 95% CI 2.17–10.60; p=0.0004) compared with patients with early or without AFOP, and elevated airway and blood eosinophilia (p=0.043 and p=0.045, respectively) compared with early AFOP patients. Late new-onset AFOP is associated with a worse prognosis and high risk of CLAD development, specifically restrictive allograft syndrome. Our findings indicate that late new-onset AFOP might play a role in the early pathogenesis of restrictive allograft syndrome.
Trends in Provision of Palliative Radiotherapy and Chemotherapy Among Hospices in the United States, 2011-2018
Authors: Sylvia H. Hsu, Shi-Yi Wang
Journal: JAMA Oncology (2020)

This case series study uses Medicare 2011-2019 Hospice Cost Report Data to analyze trends in the proportion of freestanding hospices in the United States providing radiotherapy and chemotherapy, as well as the expenses incurred for providing these therapies.
A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice
Authors: Ana Maria Valencia-Hernandez, Wei Yi Ng, Nazanin Ghazanfari, Sonia Ghilas, Maria N. de Menezes, Lauren E. Holz, Cheng Huang, Kieran English, Myo Naung, Peck Szee Tan, Kirsteen M. Tullett, Thiago M. Steiner, Matthias H. Enders, Lynette Beattie, Yu Cheng Chua, Claerwen M. Jones, Anton Cozijnsen, Vanessa Mollard, Yeping Cai, David G. Bowen, Anthony W. Purcell, Nicole L. La Gruta, Jose A. Villadangos, Tania de Koning-Ward, Alyssa E. Barry, Winfried Barchet, Ian A. Cockburn, Geoffrey I. McFadden, Stephanie Gras, Mireille H. Lahoud, Patrick Bertolino, Ralf B. Schittenhelm, Irina Caminschi, William R. Heath, Daniel Fernandez-Ruiz
Journal: Cell Host & Microbe (2020)
Culprit Tumor as an Unexpected Extraosseous MDP Activity on Bone Scintigraphy in a Patient With Tumor-Induced Osteomalacia
Authors: Xiaotian Xia, Fuqiang Shao, Fan Hu, Yongkang Gai, Xiaoli Lan
Journal: Clinical Nuclear Medicine (2020)

A 39-year-old man with bone pain underwent Tc-MDP bone scan to assess skeletal lesions, which demonstrated multiple fractures and a focus of subtle extraosseous activity in the left thigh. A Tc-hynic-octreotide imaging was performed due to the suspected diagnosis of tumor-induced osteomalacia, which revealed a hypermetabolic subcutaneous nodule in the left thigh, which exactly corresponded to the same site of MDP activity. Biopsy confirmed the subcutaneous nodule as the culprit tumor of tumor-induced osteomalacia. Bone scan, as a conventional imaging, provided useful information for detecting culprit tumor as shown in our case.
Oral squamous cell carcinoma originating from bone marrow-derived cells.
Authors: Hitoshi Kawamata, Yutaka Doi, Yoshiko Kakuta, Yasuhiro Shinagawa, Tadaaki Sasaki, Yutaka Imai
Journal: Cancer Research (2006)

5263  Several studies have shown that bone marrow cells have the potential to differentiate into variety of cell types. Here we show a case of oral squamous cell carcinoma (SCC) arisen in a patient with mixed lineage leukemia (MLL), and we also attempt to identify the origin of the oral SCC cells in the patient. The patient was a 58-year-old man, who had received peripheral blood stem cell transplantation (PBSCT) from his sister. Although MLL was successfully treated, chronic graft-versus-host disease (GVHD) developed on his skin and oral mucosa on three months after PBSCT. Then the patient was treated with immunosuppressants and steroids, however chronic GVHD was not completely controlled. Five years after PBSCT, SCC developed on his left mandibular gingiva. At that time, MLL was well controlled, then the patient received the surgical resection of oral SCC. In order to identify the origin of the oral SCC cells, we examined the chromosome pattern of oral SCC cells and normal appeared oral mucosa by fluorescent in situ hybridization. Surprisingly, most of the cancer cells (96.4%) showed XX pattern, and some of squamous cells (19%) in normal appeared oral mucosa showed XX pattern. We confirmed the chromosome pattern in the cancer cells and normal squamous cells by PCR to amplifying SRY and AMG genes. These results suggest that bone marrow-derived epithelial cells may be distributed in every part of oral mucosa during epithelial regeneration after chronic inflammation such as GVHD, and oral SCC can originate from bone marrow-derived cells.
New WHO guidelines on the management of pregnancy and breastfeeding in the context of Ebola
Authors: Anna E Thorson, Megan E Foeller, Severine Caluwaerts, Carolina Ribeiro do Valle, Ian Crozier, Gibrilla Deen, Devika Dixit, Chrissy Godwin, Pius Okong, Rachel Esteves Soeiro, João Paulo Sousa, Michel van Herp, Maurice Bucagu, Alejandro Costa, Megan Foeller, Pierre Formenty, Roopan Gill, Caron Kim, Brigitte Kini, Anais Legand, Olufemi Oladapo, Leopold Ouedraogo, Mark Perkins, Anne Thorson, Patricia Titulaer
Journal: The Lancet Infectious Diseases (2020)
Comparative evaluation of the treatment efficacy of suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer cell lines and primary ovarian cancer cells from patients
Authors: Jürgen Sonnemann, Pampa J. Kudigana, Ralf Ohlinger, Antje Belau, James F. Beck
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

2169 

In most patients (>80%) with ovarian cancer, diagnosis occurs after the tumor has disseminated beyond the ovaries. In these cases, a combination treatment with surgery and chemotherapy is necessary. The “gold standard” post-surgical first-line chemotherapy for ovarian cancer is a paclitaxel/platinum combination. However, most of the patients, though initially responsive, typically experience disease relapse and eventually die due to the emergence of resistance to these conventional drugs. In the present study, we compared paclitaxel to the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) for their treatment efficacy in patient-derived ovarian cancer cells. Inhibitors of histone deacetylases have emerged recently as a promising new generation of antineoplastic agents. Initially, we compared the cytotoxic activities of paclitaxel and SAHA by employing the ovarian carcinoma cell lines OVCAR-3, SK-OV-3, and A2780. At the concentrations applied (3-300 nM palitaxel, 1-20 μM SAHA), the drugs induced comparable cytotoxicity in all three cell lines. To compare the potential activities of paclitaxel and SAHA against ovarian carcinoma cells ex vivo, we performed cytotoxicity assays with cell isolates from five patients with primary ovarian cancer. The cells were isolated from malignant ascites collected from untreated patients with stage IV ovarian carcinomas. SAHA evoked a dose-dependent cytotoxic effect in all five isolates. A 72-h exposure to 20 μM SAHA resulted in 21% to 63% cell killing. In contrast, four of the five isolates were resistant to paclitaxel (i.e., <10% cell death at 300 nM paclitaxel for 72 hours). Only one isolate was susceptible to paclitaxel, with 21% cell killing observed at 72 hours by 300 nM of paclitaxel. In order to verify these results by a second read-out, we assessed whether paclitaxel and SAHA would activate caspase-3 in ovarian cancer cells. In the three cell lines, both paclitaxel and SAHA activated caspase-3. In the patient-derived cancer cells, treatment with SAHA led to a dose-dependent increase in caspase-3 activity in all five isolates, while treatment with paclitaxel had no effect on caspase-3 activity in three of them. These findings raise the possibility that SAHA may prove effective in the treatment of paclitaxel-resistant ovarian cancer.
Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients: results from a randomised phase III study
Authors: M. van der Meulen, K. Bakunina, M. Nijland, M.C. Minnema, G. Cull, W.B.C. Stevens, J.W. Baars, K.D. Mason, A. Beeker, M. Beijert, M.J.B. Taphoorn, M.J. van den Bent, S. Issa, J.K. Doorduijn, J.E.C. Bromberg, L. Dirven
Journal: Annals of Oncology (2020)
Hematologic adverse events associated with temozolomide (TMZ)
Authors: J. L. Villano, N. Letarte, J. M. Yu, A. R. Shakir, L. Bressler
Journal: Journal of Clinical Oncology (2009)

2053 Background: Secondary acute myeloid leukemia (AML) is reported to occur in 3%-10% of patients treated with alkylating agents for Hodgkin's lymphoma, non-Hodgkin's lymphoma, ovarian cancer, breast cancer, and multiple myeloma. The incidence of secondary AML is greatest at 5–10 years after treatment, and AML often follows myelodysplastic syndrome (MDS). TMZ is a pro-drug of methyl-triazeno-imidazole-carboxamide (MTIC), an alkylating metabolite of dacarbazine. Chemotherapy induced aplastic anemia is usually dose-related versus an idiosyncratic mechanism. A small number of fatal cases of TMZ-induced aplastic anemia have been reported. The FDA, in a Drug Safety Newsletter, described 18 cases of aplastic anemia reported between 1999 and 2006. TMZ use in brain tumors and in melanoma is increasing, with little known on the incidence of severe hematologic adverse events. Methods: We searched the FDA MedWatch database for TMZ and obtained all entries submitted to the FDA from November 1, 1997 to September 3, 2008. We also obtained the number of aplastic anemia cases reported from Schering Plough's Global Pharmacovigilance department, as of December 13, 2007. Results: During this time period, 5,127 reports (on any side effect) on 3,490 patients were submitted to MedWatch. Among these patients, we identified 140 cases that we labeled as major hematologic adverse events: agranulocytosis (8 cases), aplasia (42), aplastic anemia (52), leukemia (26), MDS (6), and lymphoma (6). Gender was reported in 133 cases. Of these, 56 were male and 77 were female. The overall mean age in cases of major hematologic adverse events was 54 years. Schering Plough reports 25 cases of aplastic anemia and estimates the frequency to be 10.22 per 100,000 patients exposed to TMZ. Conclusions: TMZ's major hematologic adverse event profile seems to differ compared with other alkylating chemotherapy. Aplastic anemia is a significant concern with TMZ use and should be disclosed to patients. Risk of leukemia/MDS from our review may also be significant, but length of follow-up is insufficient and the real risk is likely still unknown. No significant financial relationships to disclose.
Peter John Watkins
Authors: S A Amiel, M Edmonds
Journal: BMJ (2020)

Peter John Watkins was one of the great clinical diabetologists: a man of great abilities and stature, a brilliant clinician, a respected teacher, and a valued mentor, colleague and friend. Serving as consultant physician to King’s College Hospital for over 30 years, he identified himself definitively as a King’s man, but his influence spread far beyond the borders of south London.

Peter obtained his first degree in Cambridge in 1958 and completed his clinical training at St Bartholomew’s Hospital in 1962. There was a history of medicine in the Watkins family; six generations had been doctors, ranging from Timothy Watkins, a surgeon apothecary in the 18th century to Peter’s father, Kenneth Harold Watkins (1903-38), a urological surgeon at Manchester Royal Infirmary. Peter’s sister, Sylvia, was a medical oncologist, and Peter was delighted when his elder daughter, Julia, decided to study medicine also and become a clinical oncologist. Peter learned his diabetes from Professor John Malins and Dr Mike Fitzgerald at the General Hospital, Birmingham. In 1971, Peter was appointed consultant physician at King’s College Hospital, joining Dr David Pyke in the diabetes department, thus forming the remarkable Pyke and Watkins partnership that spanned the next 15 years.

Watkins and Pyke were determined to carry on the legacy of diabetes care at King’s that had started with Robin Lawrence, a surgeon and physician himself and one of the first people in the UK to receive insulin. Peter was proud of that history but was always an innovator in providing diabetes …
The sense of obligation is culturally modulated
Authors: Andrea Bender
Journal: Behavioral and Brain Sciences (2020)

Abstract Tomasello argues in the target article that, in generalizing the concrete obligations originating from interdependent collaboration to one's entire cultural group, humans become “ultra-cooperators.” But are all human populations cooperative in similar ways? Based on cross-cultural studies and my own fieldwork in Polynesia, I argue that cooperation varies along several dimensions, and that the underlying sense of obligation is culturally modulated.