Johns Hopkins University

About: Johns Hopkins University is a education organization based out in Baltimore, Maryland, United States. It is known for research contribution in the topics: Population & Health care. The organization has 110248 authors who have published 249247 publications receiving 14084474 citations. The organization is also known as: The Johns Hopkins University & Johns Hopkins.

The Prevalence of BRCA2 Mutations in Familial Pancreatic Cancer

Abstract: Mutations in the BRCA2 gene have been implicated in pancreatic cancer susceptibility through studies of high-risk breast and ovarian cancer families. To determine the contribution of mutations in BRCA2 to familial pancreatic cancer, we screened affected probands from 151 high-risk families identified through pancreatic cancer clinics for germ-line BRCA2 mutations. Of these families, 118 had two or more first- and second-degree relatives with pancreatic cancer, and an additional 33 had two or more affected second-degree relatives. The average age of onset for pancreatic cancer was 62.8 years. Five BRCA2 truncating mutations were identified, three in families with two or more first- and second-degree relatives with pancreatic cancer. Three of the families with mutations had a history of breast cancer but not ovarian cancer. Four of five families with mutations were identified through probands with early-onset (<55 years) pancreatic cancer. The results of this study were combined with those from a BRCA2 mutation study of 29 other families from the same Johns Hopkins University National Familial Pancreatic Tumor Registry to estimate the frequency of BRCA2 mutations. A total of 10 carriers from 180 families were identified, suggesting that BRCA2 mutations account for 6% of moderate and high-risk pancreatic cancer families.

A Steady-Hand Robotic System for Microsurgical Augmentation

Abstract: This paper reports the development of a robotic system designed to extend a human’s ability to perform small-scale (sub-millimeter) manipulation tasks requiring human judgement, sensory integration and hand-eye coordination. Our novel approach, which we call “steady hand” micromanipulation, is for tools to be held simultaneously both by the operator’s hand and a specially designed actively controlled robot arm. The robot’s controller senses forces exerted by the operator on the tool and by the tool on the environment, and uses this information in various control modes to provide smooth, tremor-free precise positional control and force scaling. Our goal is to develop a manipulation system with the precision and sensitivity of a machine, but with the manipulative transparency and immediacy of handheld tools for tasks characterized by compliant or semi-rigid contacts with the environment.

An env-like protein encoded by a Drosophila retroelement: evidence that gypsy is an infectious retrovirus.

Abstract: The gypsy element of Drosophila differs from most LTR retrotransposons in containing a third open reading frame that resembles retroviral env genes The protein encoded by ORF3 is glycosylated and processed, like all retroviral envelope proteins The protein is expressed at high levels in fly strains in which gypsy elements are active In these strains the protein is found primarily in viral particles When larvae of fly strains in which gypsy is normally inactive are exposed to sucrose gradient fractions containing these particles, a high level of gypsy insertion activity is observed in their progeny Thus, gypsy has the expected properties of an insect retrovirus

Involvement of macrophage mannose receptor in the binding and transmission of HIV by macrophages.

Abstract: The human immunodeficiency virus (HIV) is an enveloped virus whose surface glycoprotein gp120 binds CD4 on target cell membranes to initiate infection. About half of the carbohydrates on gp120are terminally mannosylated, a pattern common to many pathogens. We have examined the ability of macrophage mannose receptor (MMR) on primary monocyte-derived macrophages to bind HIV and facilitateits transmission to T cells. We adapted the tyramide signal amplification system for fluorescence detection of HIV bound to macrophages. Our data show that approximately 60% of the initial association of HIV with macrophages that lack expression of DC-SIGN (a dendritic cell-specific ICAM-3 receptor/HIV-1-binding protein) is MMR mediated, as evidenced by inhibition with mannan, D-mannose, EDTA, and soluble mannose-binding lectin, but not by D-galactose. This inhibition is not seen in cells that lack MMR. Macrophages are able to mediate transmission of bound HIV to co-cultured T cells, and this transmission is blocked up to 80% by inhibitors of MMR binding. Unlike virus bound to DC-SIGN, macrophage-bound HIV has a slightly lower half-life compared to free virus, with no transmission in co-culture observed beyond 24 h after virus binding to macrophages. Results obtained with endocytosis inhibitors indicate that this decrease in viral longevity is due to rapid internalization of macrophage-bound HIV. Together, these results suggest a substantial role for MMR in the binding and transmission of HIV-1 by macrophages.

Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group Study AALL0232

Abstract: PurposeSurvival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children’s Oncology Group study AALL0232 tested two interventions to improve survival.Patients and MethodsBetween January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1.ResultsPlanned interim monitoring showed the superiority of the high-dose methotrexate regimens, which exceeded the predefined boundary and led to cessation of enrollment in January 2011. At that time, participants randomly assigned to high-dose methotrexate during interim maintenance 1 versus those randomly assigned t...