tbuckley/cabot-search huggingface dataset:
Low Birth Weight and Respiratory Disease in Adulthood
Authors: Eric C. Walter, William J. Ehlenbach, David L. Hotchkin, Jason W. Chien, Thomas D. Koepsell
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The proportion of low and very low birth weight births is increasing. Infants and children with a history of low and very low birth weight have an increased risk of respiratory illnesses, but it is unknown if clinically significant disease persists into adulthood.To determine if a history of low birth weight is associated with hospitalization for respiratory illness in adulthood.This study was a population-based, case-control study. Cases were adults 18 to 27 years of age who were hospitalized for a respiratory illness from 1998 to 2007 within Washington State who could be linked to a Washington State birth certificate for the years 1980 to 1988. Four control subjects, frequency matched by birth year, were randomly selected from Washington State birth certificates for each case patient. Control subjects who died before age 18 were excluded.Two levels of exposure were identified: (1) very low birth weight (birth weight <1,500 g) and (2) moderately low birth weight (birth weight, 1,500-2,499 g). Normal birth weight individuals (2,500-4,000 g) were considered unexposed. Respiratory hospitalizations were defined using discharge diagnosis codes. Logistic regression was used to calculate the odds ratio for hospitalization comparing exposed and unexposed individuals. A total of 4,674 case patients and 18,445 control subjects were identified. The odds ratio for hospitalization for respiratory illness was 1.83 for very low birth weight (95% confidence interval, 1.28-2.62; P = 0.001) and 1.34 for moderately low birth weight (95% confidence interval, 1.17-1.53; P < 0.0005). This association remained after adjustment for birth year, sex, maternal age, race, residence, and marital status.Adults with a history of very low birth weight or moderately low birth weight were at increased risk of hospitalization for respiratory illness.
Efficient lentiviral vector-mediated control of HIV-1 replication in CD4 lymphocytes from diverse HIV+ infected patients grouped according to CD4 count and viral load
Authors: Laurent M Humeau, Gwendolyn K Binder, Xiaobin Lu, Vladimir Slepushkin, Randall Merling, Patricia Echeagaray, Mario Pereira, Tatiana Slepushkina, Scott Barnett, Lesia K Dropulic, Richard Carroll, Bruce L Levine, Carl H June, Boro Dropulic
Journal: Molecular Therapy (2004)

We present preclinical studies that demonstrate in vitro the feasibility and efficacy of lentivirus-based vector antisense gene therapy for control of HIV replication in primary T lymphocytes isolated from HIV-infected patients discordant for clinical status. VRX496 is a VSV-G-pseudotyped HIV-based vector that encodes an antisense payload against the HIV envelope gene. The antisense payload is under the control of the native LTR promoter, which is highly transactivated by tat upon HIV infection in the cell. Transfer of autologous CD4+ T lymphocytes genetically modified with VRX496 (VRX496T) into HIV-infected patients is intended to provide a reservoir of cells capable of controlling HIV, potentially delaying AIDS onset. To determine the patient population likely to respond to VRX496 for optimal efficacy, we examined the ability of our research vector, VRX494, to modify and suppress HIV in vitro in lymphocytes isolated from 20 study subjects discordant for CD4 count and viral load. VRX494 is analogous to the clinical vector VRX496, except that it contains GFP as a marker gene instead of the 186-tag marker in the clinical vector. To transfer VRX494 to target cells we developed a novel scalable two-step transduction procedure that has been translated to the clinic in an ongoing clinical trial. This procedure achieved unprecedented transduction efficiencies of 94 ± 5% in HIV+ study subject cells. In addition the vector inhibited HIV replication ≥93% in culture regardless of the viral load or CD4 count of the subject or tropism of the virus strain with which they were infected. These findings demonstrate that VRX496T therapy is expected to be beneficial to patients that differ in their status in term of CD4 count and viral load. The methods described represent significant technical advances facilitating execution of lentivirus vector-mediated gene therapy for treatment of HIV and are currently being employed in the first trial evaluating lentivirus vector safety in humans.
Broadening the Spectrum of Diseases Related to Podocin Mutations
Authors: Gianluca Caridi, Roberta Bertelli, Marco Di Duca, Monica Dagnino, Francesco Emma, Andrea Onetti Muda, Francesco Scolari, Nunzia Miglietti, Gianna Mazzucco, Luisa Murer, Alba Carrea, Laura Massella, Gianfranco Rizzoni, Francesco Perfumo, Gian Marco Ghiggeri
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. A total of 179 children with sporadic nephrotic syndrome were screened for podocin mutations: 120 with steroid resistance, and 59 with steroid dependence/frequent relapses. Fourteen steroid-resistant patients presented homozygous mutations that were associated with early onset of proteinuria and variable renal lesions, including one case with mesangial C3 deposition. Single mutations of podocin were found in four steroid-resistant and in four steroid-dependent; five patients had the same mutation (P20L). Among these, two had steroid/cyclosporin resistance, two had steroid dependence, and one responded to cyclosporin. The common variant R229Q of podocin, recently associated with late-onset focal segmental glomerulosclerosis, had an overall allelic frequency of 4.2% versus 2.5% in controls. To further define the implication of R229Q, a familial case was characterized with two nephrotic siblings presenting the association of the R229Q with A297V mutation that were inherited from healthy mother and father, respectively. Immunohistochemistry with anti-podocin antibodies revealed markedly decreased expression of the protein in their kidneys. All carriers of heterozygous coding podocin mutation or R229Q were screened for nephrin mutation that was found in heterozygosity associated with R229Q in one patient. Finally, podocin loss of heterozygosity was excluded in one heterozygous child by characterizing cDNA from dissected glomeruli. These data outline the clinical features of sporadic nephrotic syndrome due to podocin mutations (homozygous and heterozygous) in a representative population with broad phenotype, including patients with good response to drugs. The pathogenetic implication of single podocin defects per se in proteinuria must be further investigated in view of the possibility that detection of a second mutation could have been missed. A suggested alternative is the involvement of other gene(s) or factor(s). E-mail: [email protected]
Progenitor cell hyperplasia with rare development of myeloid leukemia in interleukin 11 bone marrow chimeras.
Authors: R G Hawley, A Z Fong, B Y Ngan, V M de Lanux, S C Clark, T S Hawley
Journal: The Journal of Experimental Medicine (1993)

Post 5-fluorouracil-treated murine bone marrow cells infected with a recombinant retrovirus (murine stem cell virus-interleukin 11 [MSCV-IL-11]) bearing a human IL-11 gene were transplanted into lethally irradiated syngeneic mice. Analysis of proviral integration sites in DNA prepared from hematopoietic tissues and purified cell populations of long-term reconstituted primary and secondary recipients demonstrated polyclonal engraftment by multipotential stem cells. High levels (100-1,500 U/ml) of IL-11 were detected in the plasma of the MSCV-IL-11 mice. Systemic effects of chronic IL-11 exposure included loss of body fat, thymus atrophy, some alterations in plasma protein levels, frequent inflammation of the eyelids, and often a hyperactive state. A sustained rise in peripheral platelet levels (approximately 1.5-fold) was seen throughout the observation period (4-17 wk). No changes were observed in the total number of circulating leukocytes in the majority of the transplanted animals (including 10 primary and 18 secondary recipients) despite a &amp;gt; 20-fold elevation in myeloid progenitor cell content in the spleen. The exceptions were members of one transplant pedigree which presented with myeloid leukemia during the secondary transplant phase. A clonal origin of the disease was determined, with significant expansion of the MSCV-IL-11-marked clone having occurred in the spleen of the primary host. Culturing of leukemic spleen cells from a quaternary recipient led to the establishment of a permanent cell line (denoted PGMD1). IL-11-producing PGMD1 myeloid leukemic cells are dependent on IL-3 for continuous growth in vitro and they differentiate into granulocytes and macrophages in response to granulocyte/macrophage colony-stimulating factor. The inability of autogenously produced IL-11 to support autonomous growth of PGMD1 cells argues against a mechanism of transformation involving a classical autocrine loop.
A Community Based Approach to Reducing Hispanic Pediatric Asthma Disparities: A Collaborative Effort to Deliver Care between a Bicultural Bilingual Allergist/Immunologist (BC/BL/A/I)and Community Health Workers (CHWs)
Authors: J.J. Kulik, L.G. Hwang, C.A. Jackson, J. Mora, J.N. Moy, G.S. Mosnaim
Journal: Journal of Allergy and Clinical Immunology (2006)
Tight junction proteins ZO-1, ZO-2, and occludin along isolated renal tubules
Authors: Lorenza Gonzalez-Mariscal, Maria C. Namorado, Dolores Martin, Jose Luna, Lourdes Alarcon, Socorro Islas, Laura Valencia, Pablo Muriel, Lissette Ponce, Jose L. Reyes
Journal: Kidney International (2000)
Paradoxical movement of the lower ribcage at rest and during exercise in COPD patients
Authors: A. Aliverti, M. Quaranta, B. Chakrabarti, A. L. P. Albuquerque, P. M. Calverley
Journal: European Respiratory Journal (2008)

Paradoxical inward displacement of the costal margin during inspiration is observed in many chronic obstructive pulmonary disease patients at rest but its importance is unclear. The current authors studied 20 patients (forced expiratory volume in one second 32.6±11.7, functional residual capacity 186±32% predicted) and 10 healthy controls at rest and during symptom-limited incremental exercise. With optoelectronic plethysmography, the phase shift between pulmonary and abdominal ribcage volumes and the percentage of inspiratory time the ribcage compartments moved in opposite directions were quantified, using control data to define the normal range of movement. Eight patients showed lower ribcage inspiratory paradox at rest (P+), while 12 patients did not (P-). This was unrelated to resting lung function or exercise tolerance. Total end-expiratory chest wall volume (EEV<sub>cw</sub>) increased immediately when exercise began in P+ patients, but later in exercise in P- patients. This difference in EEV<sub>cw</sub> was mainly due to a greater increase of end-expiratory pulmonary ribcage volume in P+ patients. During exercise, dyspnoea increased similarly in the two groups, while leg effort increased more markedly in the patients without paradox. In conclusion, lower ribcage paradox at rest is reproducible and associated with early-onset hyperinflation of the chest wall and predominant dyspnoea at end-exercise. When paradox is absent, the sense of leg effort becomes a more important symptom limiting exercise.
Phase I Study of YM155, a Novel Survivin Suppressant, in Patients with Advanced Solid Tumors
Authors: Taroh Satoh, Isamu Okamoto, Masaki Miyazaki, Ryotaroh Morinaga, Asuka Tsuya, Yoshikazu Hasegawa, Masaaki Terashima, Shinya Ueda, Masahiro Fukuoka, Yutaka Ariyoshi, Toshikazu Saito, Noriyuki Masuda, Hirokazu Watanabe, Tetsuo Taguchi, Toru Kakihara, Yumiko Aoyama, Yohko Hashimoto, Kazuhiko Nakagawa
Journal: Clinical Cancer Research (2009)

YM155, a novel molecular targeted agent, suppresses survivin, a member of the inhibitor of apoptosis protein family that is overexpressed in many tumor types. The aim of this study was to determine the maximum tolerated dose (MTD) and to assess the safety, pharmacokinetics, and antitumor activity of YM155 in patients with advanced refractory solid tumors.Patients with advanced refractory solid tumors were treated with escalating doses of YM155 administered by continuous i.v. infusion for 168 hours in 21-day cycles.Of the 34 patients enrolled, 33 (median age, 59 years) received at least 1 dose of YM155 (range, 1-19 cycles). The dose levels studied were 1.8, 3.6, 4.8, 6.0, 8.0, and 10.6 mg/m(2)/d. The MTD was determined to be 8.0 mg/m(2)/d, based on a dose-limiting toxicity of increased blood creatinine observed in 2 patients receiving 10.6 mg/m(2)/d. The most common adverse reactions judged to be related to YM155 were urine microalbumin present; fever; injection-site phlebitis; fatigue; and decreased hemoglobin/anemia, blood albumin, and lymphocyte count. The pharmacokinetic profile was almost linear over the dosing range and was similar between cycles 1 and 2. Urinary excretion of YM155 showed no definite difference among doses. Stable disease was achieved in nine patients.YM155 was safely administered to patients with advanced refractory solid tumors by 168-hour continuous i.v. infusion in 21-day cycles. The MTD was determined to be 8.0 mg/m(2)/d. The safety profile, plasma concentrations achieved, and antitumor activity observed merit further studies with this survivin suppressant, alone and in combination regimens.
Time course of brachial artery diameter responses to rhythmic handgrip exercise in humans
Authors: J Shoemaker
Journal: Cardiovascular Research (1997)

Objective: Whether the dimensions of conduit arteries contribute to the time course of change in blood flow during voluntary rhythmic exercise, and the mechanisms governing such a response in humans, are not known. Methods: The time course of change in the vascular and blood flow dynamics in the brachial artery during the transition between rest and 5 min of rhythmic handgrip exercise was assessed in humans using continuous measures of brachial artery mean blood velocity (MBV; pulsed Doppler), diameter (echo Doppler) and mean arterial pressure (Finapres). The exercise cadence was 1s/1s (Fast) and 1s/2s (Slow) work/rest schedules while supine with the arm positioned above or below the heart. Results: Brachial artery diameter of the active arm was reduced 5% at ∼10 s following the onset of exercise performed above the heart (P<0.05), irrespective of work rate, and returned to rest levels by 30 s with no concurrent changes in arterial pressure. By 2 min of the Fast contraction rate exercise, brachial artery diameter of the active arm was greater than rest (P<0.05) irrespective of arm position. Brachial artery dimensions in the contralateral inactive arm were not altered during exercise (P >0.05). Compared with rest, MBV and forearm blood flow at 5 s of exercise were increased in the active arm but were reduced transiently in the inactive limb (P<0.05). Conclusions: Conduit artery responses to exercise were dependent upon the work rate and arm position. The delayed dilation in the heavier exercise, independent of arm position, suggests that stimuli related to the metabolic activity of the distal active skeletal muscle may influence the dimensions of the conduit artery.
INSULIN SHOCK THERAPY, A STATISTICAL SURVEY OF 393 CASES
Authors: D. M. PALMER, J. P. RIEPENHOFF, P. W. HANAHAN
Journal: American Journal of Psychiatry (1950)

1. Insulin shock therapy was found to be effective in the treatment of 182 cases of schizophrenia in the following terms : discharged from the hospital, 34.1% ; remained discharged after a period of 21 to 75. months, 19.8% ; and full social recovery (after that period of time) estimated at about 6%. These figures indicate that insulin shock therapy is certainly not sufficient as a sole form of treatment in schizophrenia. It may have more value when used as a preliminary approach to psychotherapy or milieu therapy. On the other hand the low social recovery rate, after 40 months (average) of evaluation, is discouraging. 2. Race was not a significant factor in this form of therapy. 3. The older the patient the better the remission status following therapy, i. e., fewer relapses occurred. 4. There was no indication that insulin shock therapy is especially effective in any particular type of schizophrenic reaction. 5. The effectiveness was found to decrease as the length of illness prior to therapy was increased. 6. Of 182 schizophrenic patients showing remission after a course of insulin shock therapy as the first form of shock treatment, 41.9% later suffered relapses, within a time evaluation period averaging 3⅓ years. 7. Insulin shock therapy was effective in some patients (17.0% of cases) who had failed to respond with electroshock treatment. 8. Electroshock therapy was effective in some patients (15.0% of cases) who had failed to respond with insulin treatment. 9. A second course of insulin treatment was found to be of very little value if the patient had failed to respond with the first course. 10. The level of the fasting blood sugar prior to insulin shock therapy had no effect on the outcome of the treatment. 11. Almost invariably a substantial gain in weight was produced during the course of insulin shock therapy. This had little bearing on the ultimate improvement of the patient. 12. The length of treatment was of no value in estimating the prognosis. 13. Convulsive attacks during insulin coma seemed to have a favorable therapeutic effect. 14. There was no marked change in blood pressure following insulin shock therapy. 15. Paranoid schizophrenics required a smaller dosage of insulin to produce symptoms of hypoglycemia than did the other types of schizophrenia. 16. Insulin shock therapy can be expected to produce certain complications and a mortality rate of about 0.5%.
Interferon-α and Interleukin-12 Are Induced Differentially by Toll-like Receptor 7 Ligands in Human Blood Dendritic Cell Subsets
Authors: Tomoki Ito, Ryuichi Amakawa, Tsuneyasu Kaisho, Hiroaki Hemmi, Kenichirou Tajima, Kazutaka Uehira, Yoshio Ozaki, Hideyuki Tomizawa, Shizuo Akira, Shirou Fukuhara
Journal: The Journal of Experimental Medicine (2002)

Dendritic cells (DCs) play a crucial role in the immune responses against infections by sensing microbial invasion through toll-like receptors (TLRs). In humans, two distinct DC subsets, CD11c− plasmacytoid DCs (PDCs) and CD11c+ myeloid DCs (MDCs), have been identified and can respond to different TLR ligands, depending on the differential expression of cognate TLRs. In this study, we have examined the effect of TLR-7 ligands on human DC subsets. Both subsets expressed TLR-7 and could respond to TLR-7 ligands, which enhanced the survival of the subsets and upregulated the surface expression of costimulatory molecules such as CD40, CD80, and CD86. However, the cytokine induction pattern was distinct in that PDCs and MDCs produced interferon (IFN)-α and interleukin (IL)-12, respectively. In response to TLR-7 ligands, the Th1 cell supporting ability of both DC subsets was enhanced, depending on the cytokines the respective subsets produced. This study demonstrates that TLR-7 exerts its biological effect in a DC subset-specific manner.
Potential role of humoral immunity in cardiac dysfunction of patients suffering from dilated cardiomyopathy
Authors: Alexander Staudt, Yvonne Staudt, Marcus Dörr, Marco Böhm, Fabian Knebel, Astrid Hummel, Lydia Wunderle, Malte Tiburcy, Klaus D. Wernecke, Gert Baumann, Stephan B. Felix
Journal: Journal of the American College of Cardiology (2004)
Inhibitors of Histone Deacetylation Downregulate the Expression of Endothelial Nitric Oxide Synthase and Compromise Endothelial Cell Function in Vasorelaxation and Angiogenesis
Authors: Lothar Rössig, Huige Li, Beate Fisslthaler, Carmen Urbich, Ingrid Fleming, Ulrich Förstermann, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation Research (2002)

The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) inhibits hypoxia-stimulated angiogenesis. Endothelial nitric oxide synthase (eNOS)–derived NO is central to angiogenesis signaling in endothelial cells (ECs). We hypothesized that the HDAC-dependent regulation of angiogenesis may involve a modulatory effect on eNOS expression. The HDAC inhibitors TSA, butyric acid (BuA), and MS-275 time- and concentration-dependently suppressed eNOS protein levels to 41±2%, 46±12%, and 40±12% of control, respectively. In parallel, TSA and BuA also downregulated eNOS mRNA expression to 21±4% and 37±4% of control. TSA also attenuated the NO-dependent relaxation of porcine coronary arteries ( P &lt;0.0001, TSA 1 μmol/L) and prevented tube formation in a human angiogenesis assay. Although vascular endothelial growth factor substitution did not compensate for the inhibitory effect of TSA, exogenous NO reversed the inhibition of angiogenesis by TSA. To address the underlying signaling mechanism, we characterized the effect of TSA on eNOS gene transcription and mRNA half-life. Although TSA decreased both eNOS protein and mRNA levels, TSA paradoxically enhanced the activity of the eNOS promoter, and did not alter the eNOS transcription rate in nuclear run-on experiments, suggesting that TSA posttranscriptionally targets eNOS mRNA. These data indicate that HDAC-dependent mechanisms contribute to the regulation of eNOS expression in ECs.
Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma
Authors: Joshua S Manusow, Leila Khoja, Nataly Pesin, Anthony M Joshua, Efrem D Mandelcorn
Journal: Journal for ImmunoTherapy of Cancer (2014)

We report on a 36-year-old woman treated with the anti PD-1 antibody Pembrolizumab for metastatic cutaneous melanoma in the first line setting. She achieved a complete response and then relapsed with metastases to the vitreous cavity with an associated angiographically determined retinal vasculitis. Vitreous metastasis without choroidal involvement is unusual and may be due to individual cell extravasation, vitreous hemorrhage containing malignant cells, or direct spread through the optic nerve. This finding highlights the need for immune sanctuary sites to be monitored in the presence of PD-1 inhibition and we hypothesize that the use of PD-1 inhibitor potentiated the patient's angiographically determined retinal vasculitis.
Cisplatin-Induced Renal Injury Is Independently Mediated by OCT2 and p53
Authors: Jason A. Sprowl, Cynthia S. Lancaster, Navjotsingh Pabla, Edwin Hermann, Ashley M. Kosloske, Alice A. Gibson, Lie Li, Dorothea Zeeh, Eberhard Schlatter, Laura J. Janke, Giuliano Ciarimboli, Alex Sparreboom
Journal: Clinical Cancer Research (2014)

Tubular secretion of cisplatin is abolished in mice deficient for the organic cation transporters Oct1 and Oct2 (Oct1/2(-/-)mice), and these animals are protected from severe cisplatin-induced kidney damage. Since tubular necrosis is not completely absent in Oct1/2(-/-)mice, we hypothesized that alternate pathways are involved in the observed injury.Studies were done in wild-type, Oct1/2(-/-), or p53-deficient animals, all on an FVB background, receiving cisplatin intraperitoneally at 15 mg/kg. Cisplatin metabolites were analyzed using mass spectrometry, and gene expression was assessed using Affymetrix microarrays and RT-PCR arrays.KEGG pathway analyses on kidneys from mice exposed to cisplatin revealed that the most significantly altered genes were associated with the p53 signaling network, including Cdnk1a and Mdm2, in both wild-type (P = 2.40 × 10(-11)) and Oct1/2(-/-)mice (P = 1.92 × 10(-8)). This was confirmed by demonstrating that homozygosity for a p53-null allele partially reduced renal tubular damage, whereas loss of p53 in Oct1/2(-/-)mice (p53(-/-)/Oct1/2(-/-)) completely abolished nephrotoxicity. We found that pifithrin-α, an inhibitor of p53-dependent transcriptional activation, inhibits Oct2 and can mimic the lack of nephrotoxicity observed in p53(-/-)/Oct1/2(-/-)mice.These findings indicate that (i) the p53 pathway plays a crucial role in the kidney in response to cisplatin treatment and (ii) clinical exploration of OCT2 inhibitors may not lead to complete nephroprotection unless the p53 pathway is simultaneously antagonized.