tbuckley/cabot-search huggingface dataset:
The action of leucyl-leucine methyl ester on cytotoxic lymphocytes requires uptake by a novel dipeptide-specific facilitated transport system and dipeptidyl peptidase I-mediated conversion to membranolytic products.
Authors: D L Thiele, P E Lipsky
Journal: The Journal of Experimental Medicine (1990)

The mechanism of toxicity for cytolytic lymphocytes of Leu-Leu-OMe and related dipeptide derivatives was examined. Selective inhibition of dipeptidyl peptidase I (DPPI), a lysosomal thiol protease highly enriched in cytotoxic lymphocytes, prevented all natural killer (NK) toxic effects of such agents. However, many DPPI substrates were found to possess no NK toxic properties. For some such agents, this lack of NK toxicity appeared to be related to the lack of uptake by lymphocytes. In this regard, Leu-Leu-OMe was found to be incorporated by lymphocytes and monocytes via a saturable facilitated transport mechanism with characteristics distinct from previously characterized mammalian dipeptide transport processes. This novel transport process was found to be specific for dipeptides composed of selective L-stereoisomer amino acids and enhanced by hydrophobic ester or amide additions to the COOH terminus of dipeptides. Maximal rates of Leu-Leu-OMe uptake by T8 and NK cell-enriched peripheral blood lymphocytes (PBL) were four- to sixfold higher than for T4-enriched PBL or PBL depleted of Leu-Leu-OMe-sensitive cytotoxic lymphocytes. All dipeptide amides or esters with NK toxic properties were found to act as competitive inhibitors of [3H]Leu-Leu-OMe uptake by PBL. However, some NK nontoxic DPPI substrates were found to be comparable with Leu-Leu-OMe in avidity for this transport process. Such agents were noted to possess one or more hydrophilic amino acid side chains and were found not to mediate red blood cell lysis when subjected to the acyl transferase activity of DPPI. Thus, uptake by a dipeptide-specific facilitated transport mechanism and conversion by DPPI to hydrophobic polymerization products with membranolytic properties were found to be common features of NK toxic dipeptide derivatives. The presence of a previously unreported dipeptide transport mechanism within blood leukocytes and the selective enrichment of the granule enzyme, DPPI, within cytotoxic effector cells of lymphoid or myeloid lineage appear to afford a unique mechanism for the targeting of immunotherapeutic reagents composed of simple dipeptide esters or amides.
Lamin B1 mediates cell-autonomous neuropathology in a leukodystrophy mouse model
Authors: Mary Y. Heng, Shu-Ting Lin, Laure Verret, Yong Huang, Sherry Kamiya, Quasar S. Padiath, Ying Tong, Jorge J. Palop, Eric J. Huang, Louis J. Ptácχek, Ying-Hui Fu
Journal: Journal of Clinical Investigation (2013)

Adult-onset autosomal-dominant leukodystrophy (ADLD) is a progressive and fatal neurological disorder characterized by early autonomic dysfunction, cognitive impairment, pyramidal tract and cerebellar dysfunction, and white matter loss in the central nervous system. ADLD is caused by duplication of the LMNB1 gene, which results in increased lamin B1 transcripts and protein expression. How duplication of LMNB1 leads to myelin defects is unknown. To address this question, we developed a mouse model of ADLD that overexpresses lamin B1. These mice exhibited cognitive impairment and epilepsy, followed by age-dependent motor deficits. Selective overexpression of lamin B1 in oligodendrocytes also resulted in marked motor deficits and myelin defects, suggesting these deficits are cell autonomous. Proteomic and genome-wide transcriptome studies indicated that lamin B1 overexpression is associated with downregulation of proteolipid protein, a highly abundant myelin sheath component that was previously linked to another myelin-related disorder, Pelizaeus-Merzbacher disease. Furthermore, we found that lamin B1 overexpression leads to reduced occupancy of Yin Yang 1 transcription factor at the promoter region of proteolipid protein. These studies identify a mechanism by which lamin B1 overexpression mediates oligodendrocyte cell-autonomous neuropathology in ADLD and implicate lamin B1 as an important regulator of myelin formation and maintenance during aging.
DIABETIC CATARACTS IN AN INFANT
Authors: Ralph H. Major
Journal: JAMA (1925)

The occurrence of diabetic cataracts in children is extremely rare. While this complication is seen very often in older diabetic patients, Strouse and Gradle<sup>1</sup>found only two cases in children reported in the literature, to which number they added a third. One patient described by Sherrill<sup>2</sup>was a boy, aged 15, and Joslin's<sup>3</sup>patient was a girl of 12 years. The patient described by Strouse and Gradle was a girl, aged 10. Sherrill's patient died two years after operation, while Joslin's patient died in coma three years and four months after the onset of the diabetes. The patient of Strouse and Gradle was under good control at the time of their report. We have had under observation for the past year a child, who, when first seen, was 11 months old, and was suffering from bilateral cataracts and diabetes. <h3>REPORT OF CASE</h3> L. S., a boy, aged
Age at Cancer Diagnosis Among Persons With AIDS in the United States
Authors: Meredith S. Shiels, Ruth M. Pfeiffer, Eric A. Engels
Journal: Annals of Internal Medicine (2010)

Background: Studies have reported young ages at cancer diagnosis in HIV-infected persons and have suggested that HIV accelerates carcinogenesis. However, these comparisons did not account for differences in population age structures. Objective: To compare ages at diagnosis for non–AIDS-defining types of cancer that occur in both the AIDS and general populations, after adjustment for differences in age and other demographic characteristics between these populations. Design: Registry linkage study. Setting: 15 HIV/AIDS and cancer registry databases in the United States. Participants: 212 055 persons with AIDS enrolled in the U.S. HIV/AIDS Cancer Match Study from 1996 to 2007. Measurements: Comparison of age-at-diagnosis distributions for various types of cancer in both the AIDS and general populations, after adjustment for age and other demographic characteristics. Results: The proportion of person-time contributed by older persons (age ≥65 years) was far smaller in the AIDS population (1.5%) than in the general population (12.5%). Reflecting this difference, the ages at diagnosis for most types of cancer were approximately 20 years younger among persons with AIDS. However, after adjustment for differences in the populations at risk, the median ages at diagnosis in the AIDS and general populations did not differ for most types of cancer (for example, colon, prostate, or breast cancer; all P > 0.100). In contrast, ages at diagnosis of lung (median, 50 vs. 54 years) and anal cancer (median, 42 vs. 45 years) were significantly younger in persons with AIDS than expected in the general population (P < 0.001), and the age at diagnosis of Hodgkin lymphoma was significantly older (median, 42 vs. 40 years; P < 0.001). Limitations: Information on other cancer risk factors, including cigarette smoking, was not available. Analysis was restricted to non-Hispanic white and black persons who had AIDS, which could limit the generalizability of the findings to other racial and ethnic groups or to persons with HIV but not AIDS. Conclusion: For most types of cancer, the age at diagnosis is similar in the AIDS and general populations, after adjustment for the ages of the populations at risk. Modest age differences remained for a few types of cancer, which may indicate either acceleration of carcinogenesis by HIV or earlier exposure to cancer risk factors. Primary Funding Source: National Cancer Institute.
A multicentre study assessing the prevalence of sensitizations in patients with asthma and/or rhinitis in China
Authors: J. Li, B. Sun, Y. Huang, X. Lin, D. Zhao, G. Tan, J. Wu, H. Zhao, L. Cao, N. Zhong
Journal: Allergy (2009)

The prevalence of sensitization in patients with asthma and rhinitis in mainland China remains unclear.Our aim was to estimate the prevalence of allergy in patients with respiratory allergic diseases such as asthma and/or rhinitis attending respiratory clinics within mainland China. The study also investigated regional and annual differences in the prevalence and pattern of sensitization among the patients in China.A cross-sectional survey was performed in 6304 patients suffering from asthma and/or rhinitis in 17 cities from 4 regions of China. Patients completed a standardized questionnaire asking for the presence of respiratory and allergic symptoms. They also underwent skin prick tests with 13 common aeroallergens.Among the 6304 patients, 4545 (72.1%) had at least one positive skin prick reaction. The overall prevalence of positive skin prick responses was 59.0% for Dermatophagoides farinae, 57.6% for Dermatophagoides pteronyssinus, 40.7% for Blomia tropicalis, 16.1% for American cockroach, 14.0% for dog, 11.5% for Blatella germanica, 11.3% for Artemisia vulgaris, 10.3% for cat, 6.5% for Ambrosia artemisifolia, 6.3% for mixed mould I, 4.4% for mixed mould IV, 3.5% for mixed grass pollen and 2.2% for mixed tree pollen. Sensitizations to common allergens varied widely between geographical areas and demonstrated unique pattern in patients by stratification with age groups, with asthma and/or rhinitis. Severity of rhinitis and asthma was significantly correlated with skin index of reactivity to Artemisia vulgaris, Ambrosia artemisifolia and to D. pteronyssinus, D. farinae and Blomia tropicalis respectively (P < 0.001). Positive reactivity to the tested allergens and concomitant reactivity to multiple allergens including to house dust mites and Blomia tropicalis was markedly increased in patients with both asthma and rhinitis.House dust mites were the most prevalent allergens in patients with asthma and/or rhinitis in China. There were significant differences in patterns of sensitizations in patients from different geographical areas, age groups as well as asthma and/or rhinitis.
Response Monitoring to Bisphosphonate Therapy in Monostotic Paget Disease Using 18F-FDG PET/CT
Authors: Punit Sharma, Piyali Chatterjee
Journal: Clinical Nuclear Medicine (2015)

Paget disease is a benign bone disorder characterized by abnormal bone absorption and mineralization, resulting in bone deformity and fragility. Currently, bisphosphonates form the cornerstone of treatment for Paget disease. We report the case of a 67-year-old man with monostotic Paget disease, where F-FDG PET/CT was used for assessment of response to bisphosphonate therapy.
AN ANALYSIS OF EIGHT HUNDRED AND EIGHT CASES OF CHOREA, WITH SPECIAL REFERENCE TO THE CARDIO-VASCULAR MANIFESTATIONS.
Authors: W. S. THAYER
Journal: JAMA (1906)

Some time ago Dr. Thomas suggested to me that it might be of interest to analyze the records of the cases of chorea which had been treated in his department in the Johns Hopkins Hospital Dispensary with reference to the cardio-vascular manifestations. For the most part these cases have been rather carefully studied, each patient, as far as possible, having been sent to the medical department for special notes on the heart. Last fall, accordingly, I undertook this task, which was particularly interesting to me in view of the fact that many of the special notes had been made by myself. I have added to these cases those which have been treated in the hospital wards during the same period, the majority of which I have also been able to study. My plan was somewhat similar to that which was adopted a few years ago in the study of the
Long-term expansion of effector/memory Vδ2− γδ T cells is a specific blood signature of CMV infection
Authors: Vincent Pitard, David Roumanes, Xavier Lafarge, Lionel Couzi, Isabelle Garrigue, Marie-Edith Lafon, Pierre Merville, Jean-François Moreau, Julie Déchanet-Merville
Journal: Blood (2008)
F-18 FDG PET/CT Findings of a Case of Complete Hydatidiform Mole
Authors: Kazuyoshi Suga, Syougo Nawata, Yasuhiko Kawakami, Atsuto Hiyama, Kenji Hori, Naofumi Matsunaga
Journal: Clinical Nuclear Medicine (2009)

A 37-year-old patient with complete hydatidiform mole showed characteristic F-18 FDG uptake on a PET/computed tomography (CT) scan, with doughnut-like FDG uptake along the circular low CT attenuation areas in the uterine cavity and intensive FDG uptake in the right ovary. FDG-avid circular low CT attenuation areas appeared to reflect glucose hypermetabolism in the pathologic proliferation of villi with hydropic degeneration. Intensive FDG uptake in the right ovary was due to over-stimulation of gonadotropin produced by hydatidiform mole to the corpus luteum.
Nodular regenerative hyperplasia of the liver associated with the toxic oil syndrome: Report of five cases
Authors: José A. Solis-Herruzo, José V. Vidal, Francisco Colina, Fermin Santalla, Gregorio Castellano
Journal: Hepatology (1986)

Nodular regenerative hyperplasia of the liver developed in five patients who had the toxic oil syndrome caused by ingestion of adulterated cooking oil. This hepatic complication was detected from 19 to 37 months (mean-2.5 years) after the onset of the toxic oil syndrome. Nodular regenerative hyperplasia was asymptomatic, although all patients had persistently abnormal liver function. Hepatomegaly was present in four cases, mild jaundice in three and signs of portal hypertension in two. Pathogenesis of nodular regenerative hyperplasia in toxic oil syndrome is unknown, but probably microcirculatory disturbances within the liver might have played a role. Fibrosis in Zone 3, sinusoidal dilatation and occasionally intralobular hemorrhage were seen in three cases; in one of them, characteristic lesions of venoocclusive disease were also present. In another case, endarteritic changes of hepatic arterioles were evident.
New Basic Membrane-Destabilizing Peptides for Plasmid-Based Gene Delivery in Vitro and in Vivo
Authors: Karola Rittner, Annie Benavente, Albine Bompard-Sorlet, Frédéric Heitz, Gilles Divita, Robert Brasseur, Eric Jacobs
Journal: Molecular Therapy (2002)

We have designed new basic amphiphilic peptides, ppTG1 and ppTG20 (20 amino acids), and evaluated their efficiencies in vitro and in vivo as single-component gene transfer vectors. ppTG1 and ppTG20 bind to nucleic acids and destabilize liposomes consisting of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and cholesterol (3:1 mol/mol) at pH 5 and pH 7. Complexes of plasmid DNA and ppTG1 gave rise to efficient transfection in a variety of human and murine cell lines at low charge ratios ([+/−] between 1 and 2). In cell culture experiments, such vectors were superior to the membrane-destabilizing peptide KALA. In comparison with cationic lipid-, dendrimer-, and polymer-based transfection agents like Superfect, polyethylenimine (PEI), and Lipofectin, ppTG1 vectors showed good transfection efficiencies, especially at low DNA doses. Moreover, we demonstrated for the first time successful gene transfer in living animals with a single-component peptide vector. In the mouse, intravenous injection of a luciferase expression plasmid complexed with ppTG1 or ppTG20 led to significant gene expression in the lung 24 hours after injection. Structure–function studies with ppTG1, ppTG20, and sequence variants suggest that the high gene transfer activity of these peptides is correlated with their propensity to exist in α-helical conformation, which seems to be strongly influenced by the nature of the hydrophobic amino acids. We have designed new basic amphiphilic peptides, ppTG1 and ppTG20 (20 amino acids), and evaluated their efficiencies in vitro and in vivo as single-component gene transfer vectors. ppTG1 and ppTG20 bind to nucleic acids and destabilize liposomes consisting of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and cholesterol (3:1 mol/mol) at pH 5 and pH 7. Complexes of plasmid DNA and ppTG1 gave rise to efficient transfection in a variety of human and murine cell lines at low charge ratios ([+/−] between 1 and 2). In cell culture experiments, such vectors were superior to the membrane-destabilizing peptide KALA. In comparison with cationic lipid-, dendrimer-, and polymer-based transfection agents like Superfect, polyethylenimine (PEI), and Lipofectin, ppTG1 vectors showed good transfection efficiencies, especially at low DNA doses. Moreover, we demonstrated for the first time successful gene transfer in living animals with a single-component peptide vector. In the mouse, intravenous injection of a luciferase expression plasmid complexed with ppTG1 or ppTG20 led to significant gene expression in the lung 24 hours after injection. Structure–function studies with ppTG1, ppTG20, and sequence variants suggest that the high gene transfer activity of these peptides is correlated with their propensity to exist in α-helical conformation, which seems to be strongly influenced by the nature of the hydrophobic amino acids.
18F-FAZA PET Imaging Response Tracks the Reoxygenation of Tumors in Mice upon Treatment with the Mitochondrial Complex I Inhibitor BAY 87-2243
Authors: Edwin Chang, Hongguang Liu, Kerstin Unterschemmann, Peter Ellinghaus, Shuanglong Liu, Volker Gekeler, Zhen Cheng, Dietmar Berndorff, Sanjiv S. Gambhir
Journal: Clinical Cancer Research (2014)

We describe a noninvasive PET imaging method that monitors early therapeutic efficacy of BAY 87-2243, a novel small-molecule inhibitor of mitochondrial complex I as a function of hypoxia-inducible factor-1α (HIF1α) activity.Four PET tracers [(18)F-FDG, (18)F-Fpp(RGD)2, (18)F-FLT, and (18)F-FAZA] were assessed for uptake into tumor xenografts of drug-responsive (H460, PC3) or drug-resistant (786-0) carcinoma cells. Mice were treated with BAY 87-2243 or vehicle. At each point, RNA from treated and vehicle H460 tumor xenografts (n = 3 each) was isolated and analyzed for target genes.Significant changes in uptake of (18)F-FAZA, (18)F-FLT, and (18)F-Fpp(RGD)2 (P < 0.01) occurred with BAY 87-2243 treatment with (18)F-FAZA being the most prominent. (18)F-FDG uptake was unaffected. (18)F-FAZA tumor uptake declined by 55% to 70% (1.21% ± 0.10%ID/g to 0.35 ± 0.1%ID/g; n = 6, vehicle vs. treatment) in both H460 (P < 0.001) and PC3 (P < 0.05) xenografts 1 to 3 days after drug administration. (18)F-FAZA uptake in 786-0 xenografts was unaffected. Decline occurred before significant differences in tumor volume, thus suggesting (18)F-FAZA decrease reflected early changes in tumor metabolism. BAY 87-2243 reduced expression of hypoxia-regulated genes CA IX, ANGPTL4, and EGLN-3 by 99%, 93%, and 83%, respectively (P < 0.001 for all), which corresponds with reduced (18)F-FAZA uptake upon drug treatment. Heterogeneous expression of genes associated with glucose metabolism, vessel density, and proliferation was observed.Our studies suggest suitability of (18)F-FAZA-PET as an early pharmacodynamic monitor on the efficacy of anticancer agents that target the mitochondrial complex I and intratumor oxygen levels (e.g., BAY 87-2243).
Dunlop's Traction
Authors: Francis P. Keefe
Journal: JAMA (1961)

<h3>To the Editor:—</h3> Congratulations on the modifications ofThe Journalsince your editorship began. I have a minor complaint, however, concerning an article inThe Journal, Feb. 18, 1961, p. 573, entitled "Supracondylar Fractures of the Humerus in Children," which concludes that a method of reduction called Dunlop's traction is the procedure of choice. This is, a very informative article and may do a great deal to improve the handling of a somewhat difficult and always potentially dangerous fracture. There are, in the article, some 21 references to Dunlop's traction, and in the references some 18 sources are quoted, but at no time do the authors bother to explain what Dunlop's traction is. I believe that the exact application of such traction is not common knowledge, the original article by Dunlop having appeared in<i>Bone and Joint Surgery</i>, January, 1939, p. 59. When such an otherwise excellent article is presented,
Detection of Organ-Confined Prostate Cancer Is Increased Through Prostate-Specific Antigen—Based Screening
Authors: William J. Catalona, Deborah S. Smith, Timothy L. Ratliff, Joseph W. Basler
Journal: JAMA (1993)

<h3>Objective.</h3> —To determine whether prostate-specific antigen (PSA)—based screening alters the proportion of organ-confined prostate cancers detected. <h3>Design.</h3> —A prospective, nonrandomized, serial PSA-based screening trial (follow-up from 6 to 37 months), and a concurrent comparison group. <h3>Setting.</h3> —Genera community outpatient screening program based at a university center. <h3>Patients.</h3> —The study group consisted of 10251 men aged 50 years and older (mean and median age, 63 years; mean and median age of patients who underwent biopsies, 66 years) who presented to a prostate cancer screening program and consented to phlebotomy. The comparison group consisted of 266 concurrently studied private patients in the same age range (mean and median age, 68 years) who were referred for prostatic ultrasonography and biopsy because of an abnormal digital rectal examination (DRE). <h3>Main Outcome Measure.</h3> —Proportion detected with clinically or pathologically advanced prostate cancer. <h3>Results.</h3> —The men were divided into three groups: the comparison group, the initial PSA-based screening group, and the serial PSA-based screening group. The proportions of prostate cancers detected that were clinically or pathologically advanced were as follows: comparison group, 57% (27/47); initial PSA-based screening group, 37% (91/244); and serial PSA-based screening group, 29% (37/ 129). Screened patients had a lower proportion of advanced cancers than the comparison group (χ<sup>2</sup>[2]=12.3;<i>P</i>=.002); this advantage was observed principally in patients younger than 70 years. Surgical staging revealed that the cancer was microscopically focal and well differentiated (possibly latent cancer) in 2.5% (1/40) of the nonscreened group, 2.9% (7/244) of the initially screened group, and 7.8% (10/129) of the serially screened group (generalized Fisher's Exact Test,<i>P</i>=.08). <h3>Conclusion.</h3> —Screening based on PSA identifies some men with prostate cancer who have a significantly increased proportion of organ-confined tumors compared with those detected through evaluation for an abnormal DRE alone. (<i>JAMA</i>. 1993;270:948-954)
A Versatile Approach to Engineering Biomolecule‐Presenting Cellular Microenvironments
Authors: Philipp S. Lienemann, Maria Karlsson, Ana Sala, Hanna M. Wischhusen, Franz E. Weber, Roland Zimmermann, Wilfried Weber, Matthias P. Lutolf, Martin Ehrbar
Journal: Advanced Healthcare Materials (2012)

By combining a novel protein-capture hydrogel with state-of-the-art mammalian recombinant protein production, cellular microenvironments are fabricated that locally instruct in-vitro cell behavior through selective presentation of the expressed proteins. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.