tbuckley/cabot-search huggingface dataset:
Development of cytolytic T lymphocyte precursors in organ-cultured mouse embryonic thymus rudiments.
Authors: R Ceredig, E J Jenkinson, H R MacDonald, J J Owen
Journal: The Journal of Experimental Medicine (1982)

The appearance of immunologically competent cells in the organ-cultured mouse fetal thymic rudiment has been investigated. Fetal thymuses removed at 14 d of gestation and cultured for 7-21 d were assayed for their content of cytolytic T lymphocyte precursors (CTL-P) directed against H-2d alloantigens. Whereas CTL-P were undetectable within fetal thymus until 18-19 d of gestation, their frequency in the organ-cultured fetal thymus was similar to, or greater than that found in the normal adult thymus. This direct demonstration of the appearance of alloreactive CTL-P in a closed in vitro system should provide an accessible model for the investigation of interactions between developing T cells and the thymic microenvironment.
The diagnosis and management of hypercalcaemia
Authors: S. Minisola, J. Pepe, S. Piemonte, C. Cipriani
Journal: BMJ (2015)

#### The bottom line 

Hypercalcaemia is a common finding in the setting of primary care,1 as well as in emergency departments2 and patients admitted to hospital.3 Primary hyperparathyroidism and malignancy are the two most common causes of increased serum calcium levels, together accounting for about 90% of all cases.4 The remaining 10% represent an important figure, and thus the need to consider other disorders in the evaluation of patients with hypercalcaemia. This review aims to give an overview of the diagnosis and clinical management of hypercalcaemia for non-specialist clinicians and health professionals.

#### Sources and selection criteria

We carried out a search through Medline and PubMed of articles published from 1990 to 2015 using the terms “mild hypercalcaemia” and “severe “hypercalcemia”, “primary hyperparathyroidism”, “hypercalcemia of malignancy”, “parathyroid hormone measurement”, “parathyroidectomy”, and “cinacalcet” and through the National Cancer Institute using the term “hypercalcaemia”. We also retrieved personal archived references to identify …
Evidence for alteration of the vitamin D-endocrine system in blacks.
Authors: N H Bell, A Greene, S Epstein, M J Oexmann, S Shaw, J Shary
Journal: Journal of Clinical Investigation (1985)

As compared with values in white subjects, bone mass is known to be increased and urinary calcium to be diminished in black individuals. To evaluate the possibility that these changes are associated with alterations in the vitamin D-endocrine system, an investigation was performed in 12 black subjects, 7 men and 5 women, and 14 white subjects, 8 men and 6 women, ranging in age from 20 to 35 yr. All of them were hospitalized on a metabolic ward and were given a constant daily diet containing 400 mg of calcium, 900 mg of phosphorus, and 110 meq of sodium. Whereas mean serum calcium, ionized calcium, and phosphate were the same in the two groups, mean serum immunoreactive parathyroid hormone (350 +/- 34 vs. 225 +/- 26 pg/ml, P less than 0.01) and mean serum 1,25-dihydroxyvitamin D (1,25(OH)2D) (41 +/- 3 vs. 29 +/- 2 pg/ml, P less than 0.01) were significantly higher, and mean serum 25-hydroxy-vitamin D (25-OHD) was significantly lower in the blacks than in the whites (6 +/- 1 vs. 20 +/- 2 ng/ml, P less than 0.001). Mean urinary sodium and 24-h creatinine clearance were the same in the two groups, whereas mean urinary calcium was significantly lower (101 +/- 14 vs. 166 +/- 13 mg/d, P less than 0.01) and mean urinary cyclic AMP was significantly higher (3.11 +/- 0.47 vs. 1.84 +/- 0.25 nM/dl glomerular filtrate, P less than 0.01) in the blacks. Further, the blacks excreted an intravenous calcium load, 15 mg/kg body weight, as efficiently as the whites (49 +/- 3 vs. 53 +/- 3%, NS). Mean serum Gla protein was lower in blacks than in whites (14 +/- 2 vs. 24 +/- 3 ng/ml, P less than 0.02), and increased significantly in both groups in response to 1,25(OH)2D3, 4 micrograms/d for 4 d. There was a blunted response of urinary calcium to 1,25(OH)2D3 in the blacks, and mean serum calcium did not change. The results indicate that alteration of the vitamin D-endocrine system with enhanced renal tubular reabsorption of calcium and increased circulating 1,25(OH)2D as a result of secondary hyperparathyroidism may contribute to the increased bone mass in blacks. Their low serum 25-OHD is attributed to diminished synthesis of vitamin D in the skin because of increased pigment.
STUDIES OF THE HEMOLYSIS OF RED BLOOD CELLS BY MUMPS VIRUS
Authors: Liang-Wei Chu, Herbert R. Morgan
Journal: The Journal of Experimental Medicine (1950)

The conditions for the production of extra-embryonic fluids with hemolytic activity from chick embryos infected with mumps virus have been investigated. Infected fluids with strong hemolytic activity can be obtained by harvesting the fluids of 6- to 8-day-old chick embryos inoculated by the amniotic route after 5 to 6 days' incubation at 35 degrees C. Under such circumstances, the hemolytic capacity of amniotic fluids is usually much higher than that of the allantoic fluids. The hemolytic activity and infectivity of the virus have been found to be reduced or destroyed by heat, formaldehyde, and ultraviolet irradiation under conditions which leave the hemagglutinating capacity practically unchanged. Ultraviolet irradiation appeared to have a greater deleterious effect on the infectivity of the virus than on its hemolytic capacity. The marked reduction or destruction of hemolytic activity of the virus produced by certain treatments with these various agencies was not accompanied by loss of the ability of the virus to elute following its adsorption on red blood cells during the process of hemagglutination. This test for hemolytic activity, which measures a more labile property of the virus than do determinations of virus hemagglutination or virus elution, may be useful in detecting changes which occur early during degradation of the virus.
A PRELIMINARY REPORT ON ACID-RESISTING BACILLI, WITH SPECIAL REFERENCE TO THEIR OCCURRENCE IN THE LOWER ANIMALS
Authors: D. Murray Cowie
Journal: The Journal of Experimental Medicine (1900)

THE RESULTS OBTAINED IN THIS STUDY MAY BE BRIEFLY SUMMARIZED: 1. Acid-resisting bacilli are found in many of the lower animals, more especially the horse, cow, dog, guinea-pig and white rat. In the case of the rabbit and cat no such organisms were detected. 2. Many of these acid-resisting bacilli resemble the tubercle bacillus and the smegma bacillus of man. 3. The acid-resisting organisms are undoubtedly of different species and there is good reason to believe that the term smegma bacillus denotes not a definite species but rather a group of bacilli having common staining properties.
High Complete Remission Rate and Promising Outcome by Combination of Imatinib and Chemotherapy for Newly Diagnosed <i>BCR</i>-<i>ABL</i>–Positive Acute Lymphoblastic Leukemia: A Phase II Study by the Japan Adult Leukemia Study Group
Authors: Masamitsu Yanada, Jin Takeuchi, Isamu Sugiura, Hideki Akiyama, Noriko Usui, Fumiharu Yagasaki, Tohru Kobayashi, Yasunori Ueda, Makoto Takeuchi, Shuichi Miyawaki, Atsuo Maruta, Nobuhiko Emi, Yasushi Miyazaki, Shigeki Ohtake, Itsuro Jinnai, Keitaro Matsuo, Tomoki Naoe, Ryuzo Ohno
Journal: Journal of Clinical Oncology (2005)

A novel therapeutic approach is urgently needed for BCR-ABL-positive acute lymphoblastic leukemia (ALL). In this study, we assessed the efficacy and feasibility of chemotherapy combined with imatinib.A phase II study of imatinib-combined chemotherapy was conducted for newly diagnosed BCR-ABL-positive ALL in adults. Eighty patients were entered into the trial between September 2002 and January 2005.Remission induction therapy resulted in complete remission (CR) in 77 patients (96.2%), resistant disease in one patient, and early death in two patients, as well as polymerase chain reaction negativity of bone marrow in 71.3%. The profile and incidence of severe toxicity were not different from those associated with our historic chemotherapy-alone regimen. Relapse occurred in 20 patients after median CR duration of 5.2 months. Allogeneic hematopoietic stem-cell transplantation (HSCT) was performed for 49 patients, 39 of whom underwent transplantation during their first CR. The 1-year event-free and overall survival (OS) rates were estimated to be 60.0%, and 76.1%, respectively, which were significantly better than those for our historic controls treated with chemotherapy alone (P < .0001 for both). Among the current trial patients, the probability for OS at 1 year was 73.3% for those who underwent allogeneic HSCT, and 84.8% for those who did not.Our results demonstrated that imatinib-combined regimen is effective and feasible for newly diagnosed BCR-ABL-positive ALL. Despite a relatively short period of observation, a major potential of this treatment is recognized. Longer follow-up is required to determine its overall effect on survival.
PI3K Pathway Activation Provides a Novel Therapeutic Target for Pediatric Ependymoma and Is an Independent Marker of Progression-Free Survival
Authors: Hazel A. Rogers, Cerys Mayne, Rebecca J. Chapman, John-Paul Kilday, Beth Coyle, Richard G. Grundy
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Currently, there are few effective adjuvant therapies for pediatric ependymoma outside confocal radiation, and prognosis remains poor. The phosphoinositide 3-kinase (PI3K) pathway is one of the most commonly activated pathways in cancer. PI3Ks transduce signals from growth factors and cytokines, resulting in the phosphorylation and activation of AKT, which in turn induces changes in cell growth, proliferation, and apoptosis. Experimental Design: PI3K pathway status was analyzed in ependymoma using gene expression data and immunohistochemical analysis of phosphorylated AKT (P-AKT). The effect of the PI3K pathway on cell proliferation was investigated by immunohistochemical analysis of cyclin D1 and Ki67, plus in vitro functional analysis. To identify a potential mechanism of PI3K pathway activation, PTEN protein expression and the mutation status of PI3K catalytic subunit α-isoform gene (PIK3CA) was investigated. Results: Genes in the pathway displayed significantly higher expression in supratentorial than in posterior fossa and spinal ependymomas. P-AKT protein expression, indicating pathway activation, was seen in 72% of tumors (n = 169) and P-AKT expression was found to be an independent marker of a poorer progression-free survival. A significant association between PI3K pathway activation and cell proliferation was identified, suggesting that pathway activation was influencing this process. PTEN protein loss was not associated with P-AKT staining and no mutations were identified in PIK3CA. Conclusions: Our results suggest that the PI3K pathway could act as a biomarker, not only identifying patients with a worse prognosis but also those that could be treated with therapies targeted against the pathway, a strategy potentially effective in a high percentage of ependymoma patients. Clin Cancer Res; 19(23); 6450–60. ©2013 AACR.
NOTES ON OPHTHALMIC DISEASES
Authors: J. V. Solomon
Journal: BMJ (1855)

ORIGINAL CO CATIONS.611 2nd.8ince the last report the patient had rapidly snte ngth and muscular power.She walked this morig a distance of a mile, and back to the hospital, to ave a photographic likeness of herself taken, which is sent herewith, along with another which was taken pre- viously to the operation being performed.Appearance of patietit before operatiou.Appearance of patient after operation.
CIRCULATING IMMUNITY PRINCIPLES IN RAT-BITE FEVER
Authors: Yutaka Ido, Hiroshi Ito, Hidetsune Wani, Kikuzo Okuda
Journal: The Journal of Experimental Medicine (1917)

Summarizing the results that have been cited, we have proved that the blood serum of convalescents from rat-bite fever contains antibodies which are specific against the causative agent of that disease. The serum of rat-bite fever was capable of destroying the spirochetes not only in the hanging drop preparations, but also in the peritoneal cavity of guinea pigs. The guinea pigs employed for Pfeiffer's test always remained well. In the experimentally infected mice receiving intravenously or intraperitoneally serum equalling in quantity the amount of infected blood, the numbers of spirochetes were greatly decreased or they disappeared for a definite period. It is not yet clear how long after recovery from rat-bite fever the antibodies are effective in the blood of human beings, and further investigations are needed to elucidate this point. In our experiments we found that serum taken from Case I showed definite spirochetolytic and spirocheticidal properties 11 months after the onset of the disease. In Case 2, the period was 6 months, and in Case 3, 3 months following the onset of rat-bite fever.
Prognostic significance of surface marker expression on blasts of patients with de novo acute myeloblastic leukemia.
Authors: I Schwarzinger, P Valent, U Köller, C Marosi, B Schneider, O Haas, W Knapp, K Lechner, P Bettelheim
Journal: Journal of Clinical Oncology (1990)

The prognostic significance of the expression of surface membrane antigens on the blasts of 123 consecutive patients with de novo acute myeloblastic leukemia (AML) was evaluated. For this purpose, reactivity of monoclonal antibodies (mAbs) CLB-ERY3 (antiblood-group H antigen), VIM-D5 (CD15), WT1 (CD7), MY7 (CD13), MY9 (CD33), VID-1 (antihuman leukocyte antigen locus DR [anti-HLA DR]), VIM-2 (CDw65L), VIM-13 (CD14), 63D3 (CD14) and anti-TdT with leukemic blast cell populations was prospectively analyzed with respect to the rates of complete remission (CR), continuous complete remission (CCR), and survival. The overall rate of CR was 65%, the 6-year rates of overall CCR and survival were 23% and 13%, respectively (median period of patient observation, 30 months). Of all Abs tested, four (CLB-ERY3, MY7, anti-TdT, and VIM-D5) were found to be of prognostic value. Reactivity of CLB-ERY3, MY7, and anti-TdT was predictive for CR (CLB-ERY3+, 43% v CLB-ERY3-, 73%, P less than .02; MY7+, 59% v MY7-, 91%, P less than .003; TdT+, 28% v TdT-, 71%, P less than .001, respectively) and probability of survival (significantly lower survival rates: CLB-ERY3+, P less than .02; MY7+, P less than .03; and TdT+ cases, P less than .001, respectively). Reactivity of VIM-D5 was significantly associated with a higher probability of CCR (P less than .01). Our results confirm earlier reports on the prognostic significance of expression of CD13 and TdT in AML and indicate CLB-ERY3 (antiblood-group H antibody) and VIM-D5 (CD15) as further markers predictive for the clinical outcome in patients with de novo AML.
Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin.
Authors: S H Clarke, K Huppi, D Ruezinsky, L Staudt, W Gerhard, M Weigert
Journal: The Journal of Experimental Medicine (1985)

This study focuses on 10 BALB/c anti-influenza virus (A/PR/8/34) hemagglutinin antibodies that have light chains encoded by the same variable region kappa chain (V kappa) gene, V kappa 21C. A comparison of antibodies from lymphocytes of independent origin reveals the contribution of germline diversity (combinatorial joining and association) to this response. Although combinatorial joining and association contribute to sequence diversity, they appear to have little effect on the fine specificity of these antibodies. Somatic mutation, in addition to contributing to the sequence diversity of these antibodies, creates differences in their fine specificity. The extent of mutation and its effect on fine specificity can be seen by comparing antibodies of lymphocytes from the same clone. These intraclonal comparisons also indicate that somatic mutation is an ongoing process occurring at a high rate (estimated to be at least 10(-3) mutations per base pair per division) in the expressed V region heavy chain (VH) and V kappa genes. Furthermore, both the nature and distribution of these mutations suggest that amino acid replacement mutations in the light but not the heavy chain are selected for by antigen.
The long-term risk of malignant astrocytic tumors after structural brain injury—a nationwide cohort study
Authors: Tina Noergaard Munch, Sanne Gørtz, Jan Wohlfahrt, Mads Melbye
Journal: Neuro-Oncology (2014)

Neoplastic transformation of damaged astrocytes has been proposed as a possible pathological mechanism behind malignant astrocytic tumors. This study investigated the association between structural brain injuries causing reactive astrogliosis and long-term risk for malignant astrocytic tumors. The cohort consisted of all individuals living in Denmark between 1978 and 2011. The personal identification number assigned to all individuals allowed retrieval of diagnoses of traumatic brain injury, cerebral ischemic infarction, and intracerebral hemorrhage from the National Patient Discharge Register. Diagnoses of anaplastic astrocytoma and glioblastoma multiforme (World Health Organization grades III and IV) were retrieved from the Danish Cancer Registry. Rate ratios (RR's) were estimated using log-linear Poisson regression. In a cohort of 8.2 million individuals, 404 812 experienced a structural brain injury and 6152 developed a malignant astrocytic tumor. No significant association was observed 1–4 years after a structural brain injury (RR = 1.14; 95% CI: 0.87–1.46), whereas the long-term (5+ y) risk for malignant astrocytic tumors was significantly reduced (RR = 0.68; 95% CI: 0.49–0.90) compared with no injury. The specific long-term risks by type of injury were: traumatic brain injury RR = 0.32 (95% CI: 0.10–0.75); cerebral ischemic infarction RR = 0.69 (95% CI: 0.47–0.96); and intracerebral hemorrhage RR = 1.39 (95% CI: 0.64–2.60). We found no evidence for an association between structural brain injury and malignant astrocytic tumors within the first 5 years of follow-up. However, our study indicated a protective effect of astrogliosis-causing injuries 5 or more years after structural brain injury.
Physiologic manifestations of human anaphylaxis.
Authors: P L Smith, A Kagey-Sobotka, E R Bleecker, R Traystman, A P Kaplan, H Gralnick, M D Valentine, S Permutt, L M Lichtenstein
Journal: Journal of Clinical Investigation (1980)

In the course of a controlled study to evaluate different forms of immunotherapy for subjects with insect-sting hypersensitivity, we observed 11 subjects who had systemic cutaneous urticarial reactions and 3 subjects who experienced systemic anaphylaxis. With the exception of tachycardia, there were no cardiopulmonary changes in the subjects with urticaria, whereas the major manifestation of anaphylactic shock in the other three subjects was severe hypotension that was probably secondary to peripheral vasodilation. Significant abnormalities in gas exchange developed in two subjects. In one, bronchospasm precipitated a respiratory arrest followed by endotracheal intubation with mechanical ventilation. Although plasma histamine levels were not related to the development of cutaneous reactions, the plasma histamine levels correlated with the severity and duration of the cardiopulmonary changes observed during anaphylactic shock. The two subjects with the most severe shock showed evidence of intravascular coagulation characterized by a diminution of Factor V, Factor VIII, fibrinogen, and high molecular weight kininogen, as well as changes in components of the complement system. Standard therapy with epinephrine and fluids, usually recommended for the treatment of systemic anaphylaxis, did not immediately reverse either the hemodynamic or the respiratory abnormalities in the two subjects with the most severe anaphylactic shock. Hemodynamic recovery was gradual and did not seem directly related to any specific therapeutic intervention.
582 HEPATITIS B SURFACE ANTIGEN LEVELS AND SEQUENCES OF NATURAL HEPATITIS B VIRUS VARIANTS INFLUENCE THE ASSEMBLY AND SECRETION OF HEPATITIS D VIRUS
Authors: H.H. Shih, K.S. Jeng, W.J. Syu, Y.H. Huang, C.W. Su, W.L. Peng, I.J. Sheen, J.C. Wu
Journal: Journal of Hepatology (2008)
Tnk1/Kos1 Knockout Mice Develop Spontaneous Tumors
Authors: Sarasija Hoare, Kishalay Hoare, Mary K. Reinhard, Young J. Lee, S. Paul Oh, W. Stratford May
Journal: Cancer Research (2008)

Abstract Tnk1/Kos1 is a non–receptor protein tyrosine kinase implicated in negatively regulating cell growth in a mechanism requiring its intrinsic catalytic activity. Tnk1/Kos1 null mice were created by homologous recombination by deleting the catalytic domain. Both Tnk1+/− and Tnk1−/− mice develop spontaneous tumors, including lymphomas and carcinomas, at high rates [27% (14 of 52) and 43% (12 of 28), respectively]. Tnk1/Kos1 expression is silenced in tumors that develop in Tnk1+/− mice but not in adjacent uninvolved tissue, and silencing occurs in association with Tnk1 promoter hypermethylation. Tissues and murine embryonic fibroblasts derived from Tnk1/Kos1-null mice exhibit proportionally higher levels of basal and epidermal growth factor–stimulated Ras activation that results from increased Ras-guanine exchange factor (GEF) activity. Mechanistically, Tnk1/Kos1 can directly tyrosine phosphorylate growth factor receptor binding protein 2 (Grb2), which promotes disruption of the Grb2-Sos1 complex that mediates growth factor–induced Ras activation, providing dynamic regulation of Ras GEF activity with suppression of Ras. Thus, Tnk1/Kos1 is a tumor suppressor that functions to down-regulate Ras activity. [Cancer Res 2008;68(21):8723–32]
Cancer mutation signatures, DNA damage mechanisms, and potential clinical implications
Authors: Reuben S Harris
Journal: Genome Medicine (2013)

Knowledge of cancer genomic DNA sequences has created unprecedented opportunities for mutation studies. Computational analyses have begun to decipher mutational signatures that identify underlying causes. A recent analysis encompassing 30 cancer types reported 20 distinct mutation signatures, resulting from ultraviolet light, deficiencies in DNA replication and repair, and unexpectedly large contributions from both spontaneous and APOBEC-catalyzed DNA cytosine deamination. Mutational signatures have the potential to become diagnostic, prognostic, and therapeutic biomarkers as well as factors in therapy development.