tbuckley/cabot-search huggingface dataset:
MicroRNA-143 Activation Regulates Smooth Muscle and Endothelial Cell Crosstalk in Pulmonary Arterial Hypertension
Authors: Lin Deng, Francisco J. Blanco, Hannah Stevens, Ruifang Lu, Axelle Caudrillier, Martin McBride, John D. McClure, Jenny Grant, Matthew Thomas, Maria Frid, Kurt Stenmark, Kevin White, Anita G. Seto, Nicholas W. Morrell, Angela C. Bradshaw, Margaret R. MacLean, Andrew H. Baker
Journal: Circulation Research (2015)

The pathogenesis of pulmonary arterial hypertension (PAH) remains unclear. The 4 microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered.To elucidate the transcriptional regulation of the miR-143/145 cluster and the role of miR-143 in PAH.We identified the promoter region that regulates miR-143/145 microRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signaling pathways, including estrogen receptor, liver X factor/retinoic X receptor, transforming growth factor-β (Smads), and hypoxia (hypoxia response element), that regulated levels of all pri-miR stem loop transcription and resulting microRNA expression. We observed that miR-143-3p is selectively upregulated compared with miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMC-derived exosomes. Using assays with pulmonary arterial endothelial cells, we demonstrated a paracrine promigratory and proangiogenic effect of miR-143-3p-enriched exosomes from PASMC. Quantitative polymerase chain reaction and in situ hybridization showed elevated expression of miR-143 in calf models of PAH and in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role of miR-143 in experimental pulmonary hypertension in vivo in miR-143-/- and anti-miR-143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings.MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, whereas inhibition of miR-143-3p blocked experimental pulmonary hypertension. Taken together, these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology.
Peripheral Neuropathy in Hypothyroidism - an Association with Spurious Polycythemia (Gaisbock's Syndrome)<sup>1</sup>
Authors: Jane Martin, G H Tomkin, Michael Hutchinson
Journal: Journal of the Royal Society of Medicine (1983)

The neurological complications of hypothyroidism, including dementia, cerebellar ataxia, myopathy and entrapment neuropathy, are well recorded, but peripheral neuropathy has rarely been documented (Swanson et al. 1981). In this paper two patients are described who developed myxoedema and peripheral neuropathy. The first patient had a very rapid onset of myxoedema, and during observation he developed spurious polycythemia (Gaisbock's syndrome) over a period of nine days.
Oscillometric Blood Pressure Estimation: Past, Present, and Future
Authors: Mohamad Forouzanfar, Hilmi R. Dajani, Voicu Z. Groza, Miodrag Bolic, Sreeraman Rajan, Izmail Batkin
Journal: IEEE Reviews in Biomedical Engineering (2015)

The use of automated blood pressure (BP) monitoring is growing as it does not require much expertise and can be performed by patients several times a day at home. Oscillometry is one of the most common measurement methods used in automated BP monitors. A review of the literature shows that a large variety of oscillometric algorithms have been developed for accurate estimation of BP but these algorithms are scattered in many different publications or patents. Moreover, considering that oscillometric devices dominate the home BP monitoring market, little effort has been made to survey the underlying algorithms that are used to estimate BP. In this review, a comprehensive survey of the existing oscillometric BP estimation algorithms is presented. The survey covers a broad spectrum of algorithms including the conventional maximum amplitude and derivative oscillometry as well as the recently proposed learning algorithms, model-based algorithms, and algorithms that are based on analysis of pulse morphology and pulse transit time. The aim is to classify the diverse underlying algorithms, describe each algorithm briefly, and discuss their advantages and disadvantages. This paper will also review the artifact removal techniques in oscillometry and the current standards for the automated BP monitors.
Lethal autosomal recessive epidermolytic ichthyosis due to a novel donor splice-site mutation in<i>KRT10</i>
Authors: C. Covaciu, M. Castori, N. De Luca, P. Ghirri, A. Nannipieri, G. Ragone, G. Zambruno, D. Castiglia
Journal: British Journal of Dermatology (2010)

Epidermolytic ichthyosis (EI; MIM 113800), previously named bullous congenital ichthyosiform erythroderma or epidermolytic hyperkeratosis, is a rare and clinically variable defect of cornification characterized by generalized erythema, erosions, scaling and easily breaking blisters that become less frequent later in life while hyperkeratosis increases.1 EI is caused by dominant mutations in either KRT1 or KRT10, encoding keratin 1 (K1) and keratin 10 (K10), respectively.1 Usually, mutations are missense substitutions into the highly conserved α-helical rod domains of the proteins.2, 3 However, three inbred pedigrees in which EI is transmitted as a recessive trait due to KRT10 null mutations have been described.4-6
The effect of the summer 2003 heat wave on mortality in the Netherlands
Authors: J Garssen, C Harmsen, J De Beer
Journal: Eurosurveillance (2005)

In the Netherlands, between 1400 and 2200 deaths in the summer of 2003 may have been heat-related. The fact that the maximum temperatures were lower than in some other European countries, and occurred in less heavily populated areas, may have led to mortality figures that were relatively less dramatic. The temporarily increased death rates are only partly due to a forward shift of mortality. Heat-related mortality was most pronounced among the elderly in nursing homes.
Report on organ retention condemns doctors, management, and coroner
Authors: Mark Hunter
Journal: BMJ (2001)

A catalogue of deception and malpractice by an unethical pathologist, compounded by severe management failings and an evasive and paternalistic attitude towards bereaved parents, are the main findings of the long awaited inquiry into Alder Hey Hospital in Liverpool.

The report is every bit as scathing as described by the health secretary, Alan Milburn, with the bulk of its criticism aimed at pathologist Professor Dick van Velzen, who worked at Alder Hey between 1988 and 1995.

However, the report also contains caustic condemnation of coroner Roy Barter, Professor van Velzen's pathology colleagues, and the management teams of both Alder Hey Hospital and the University of Liverpool.

The report comes after a one year inquiry into how thousands of organs taken at postmortem examination—often without the parents' consent—were stored by Professor van Velzen, apparently without the knowledge of senior hospital and university officials.

The practice of obtaining organs without consent was exposed during …
Long term outcome of parapneumonic effusions in children
Authors: Kaliopi Kontouli, Elpis Hatziagorou, Fotis Kirvasislis, John Tsanakas
Journal: European Respiratory Journal (2013)

Aim: The objective of this study was the evaluation of the long term outcome of the parapneumonic effusion (PPE) in children regarding lung function and exercise tolerance.  Method: The design of the study included children with PPE 2 years after the initial infection (group A), hospitalized in 3rd Pulmonary Pediatric Department of Aristotle University of Thessaloniki in Greece between January 1994 and December 2009. A second group of healthy children was used as the control group (group B). All children performed spirometry and a symptom-limited cardiopulmonary exercise test on cycle ergometer. Exclusion criteria for both groups were asthma prior to initial infection using the stringent indexes for the predication of asthma.  Results: A total of 38 children of group A and 36 of group B were included in the study. Children of group A showed statistically significantly lower values in FVC, FEV1 and FEV1/FVC with no difference in FEF25-75 compared to group B. All children in both groups had no differences in maximal exercise capacity (VO2max). Although VO2peak was similar in both groups, slight differences were observed in ventilatory response to exercise between the two groups. Children with PPE had lower breathing reserve values and higher respiratory equivalent to oxygen (VE/VO2) during exercise compared to healthy subjects.  Conclusions: This study showed that there are no clinically significant long term effects on lung function among children with PPE compared to normal.
Immortalization in Culture of Rat Cells: A Genealogic Study<xref ref-type="fn" rid="FN2">2</xref>
Authors: T Matsumura, M Hayashi, R Konishi
Journal: JNCI Journal of the National Cancer Institute (1985)

The process of immortalization of cultured rat liver epithelial-like cells from JAR-2 rats was studied by time-lapse cinemicrography. This process was shown to be multistep. First (in the F-phase), cells were similar to those in a finitely proliferative population. Most cells terminated their proliferative life in the F-phase, while a few gained additional proliferative potential and subsequently entered into the T (transitional)-phase. In the T-phase, a population of cells maintained proliferative potential with a large fluctuation: Some cells further gained additional proliferative potential while others lost it. After a period in the T-phase, continuously dividing cells emerged (in the I-phase). The interphase period of the dividing cells in both the T- and the F-phases showed cells to distribute exponentially, consistent with transitional probability models. However, cells in the l-phase were distributed much more narrowly and were frequently close to a normal distribution. Hypothetical mechanisms of immortalization were presented on the basis of these observations.
One week triple therapy for Helicobacter pylori Reply
Authors: M C BATESON, A HARRIS, J J MISIEWICZ
Journal: Gut (1998)

Editor,—The paper by Misiewicz et al ( Gut 1997; 41 :735–9) is an important contribution which demonstrates the usefulness of lansoprazole and clarithromycin combined with either amoxycillin or metronidazole in the treatment of Helicobacter pylori infection.

However, there are some questions which arise:

(1)  Only half the patients had duodenal ulcers. There is good evidence that the response rate to eradication therapy is inferior in other patients and it is hard to justify grouping ulcer and non-ulcer patients together in the study.

(2)  Why use lansoprazole 30 mg twice daily? Optimal acid reduction should be achievable with 30 mg …
Advanced seminoma: treatment results, survival, and prognostic factors in 142 patients.
Authors: P J Mencel, R J Motzer, M Mazumdar, V Vlamis, D F Bajorin, G J Bosl
Journal: Journal of Clinical Oncology (1994)

To investigate the efficacy of chemotherapy and to assess the relationship between selected pretreatment characteristics and survival in patients with advanced seminoma.One hundred forty-two patients with advanced seminoma treated with platinum-based chemotherapy were the subject of this study. Treatment regimens included cisplatin, vinblastine, bleomycin, cyclophosphamide, and dactinomycin (VAB-6) (45 patients), a six-cycle regimen of VAB-6 alternating with etoposide and cisplatin (two patients), cisplatin and etoposide (60 patients), and etoposide and carboplatin (35 patients).One hundred thirty of 140 (93%) assessable patients treated with platinum-based therapy achieved a favorable response (complete response or a partial response with negative serum tumor markers). One hundred twenty-five patients (88%) are alive and 120 (86%) remain progression-free at a median follow-up duration of 43 months. Fifty-seven of 60 patients (95%) who were treated with cisplatin and etoposide achieved a favorable response; 55 (92%) remain progression-free. The relative risks of death or of an event (death or relapse) related to human chorionic gonadotropin (HCG) elevation were 1.8 (P = .04) and 1.96 (P = .001), respectively. The relative risks of death or of an event associated with lactate dehydrogenase (LDH) elevation were 2.6 (P = .05) and 2.7 (P = .02), respectively. All 19 patients with a mediastinal primary tumor site achieved a complete response, and 18 of 19 (95%) remain progression-free.Four cycles of cisplatin and etoposide is highly effective therapy for seminoma and is the standard therapy at our center. Elevation of the serum markers HCG and LDH were of prognostic significance, while an extragonadal primary tumor site was not associated with an adverse prognosis. Studies of tumor biology, including genetic analysis, are ongoing to determine other parameters that may correlate with response and survival.
Chronic Toxicity Study of Cyclohexanone in Rats and Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: W Lijinsky, R M Kovatch
Journal: JNCI Journal of the National Cancer Institute (1986)

A 2-year chronic toxicity assay of cyclohexanone (CAS: 108-94-1) was conducted in F344 rats and (C57BL/6 × C3H)F1 mice by administering a solution of cyclohexanone in drinking water. Two concentrations were given to rats, 6,500 and 3,300 ppm (wt/vol). Male mice received 13,000 and 6,500 ppm, while female mice were given three concentrations, 25,000,13,000, and 6,500 ppm. Each treatment group consisted of 50 or 52 male and 50 or 52 female rats or mice, except 47 male mice treated with the highest dose and 41 female mice treated with the highest dose, and there was a group of untreated controls of each species. Survival and weight gain were similar to those of controls at the lowest cyclohexanone dose in both sexes of both species, but weight gain was depressed at all of the higher doses. Survival was good (>80% at 90 wk) in all groups except in female mice at the 2 highest doses; at 25,000 ppm of cyclohexanone, only 50% of mice lived beyond 1 year. Most of the neoplasms in the treated groups did not differ significantly in number from those in the controls. Male rats receiving 3,300 ppm cyclohexanone had a 13% incidence of adrenal cortex adenomas (7 animals) compared with an incidence of 2% in controls; the incidence of this neoplasm did not increase in the male rats receiving 6,500 ppm or in the female rats given either dose. The mice had a statistically significant increase in incidence of lymphomas-leukemias among the females given 6,500 ppm, but not among the groups given higher doses of cyclohexanone. Male mice given 6,500 ppm cyclohexanone showed an increased incidence of hepatocellular adenomas and carcinomas, 50% versus 32.5% in controls, but the incidence of these neoplasms was only 37% in the male mice given 13,000 ppm cyclohexanone. The incidence of lymphomas in male mice and of hepatocellular neoplasms in female mice given cyclohexanone did not differ from that in the controls. The evidence for carcinogenic activity of cyclohexanone is marginal and the effect, if any, is weak.
Immunophenotypes and karyotypes of leukemic cells in children with Down syndrome and acute lymphoblastic leukemia.
Authors: C H Pui, S C Raimondi, M J Borowitz, V J Land, F G Behm, D J Pullen, M L Hancock, J J Shuster, C P Steuber, W M Crist
Journal: Journal of Clinical Oncology (1993)

PURPOSE Immunophenotypes and karyotypes of leukemic cells were analyzed in a large series of Down syndrome patients with acute lymphoblastic leukemia (ALL) to examine the frequency of adverse prognostic features in comparison with other patients with ALL. PATIENTS AND METHODS Presenting features and leukemic cell characteristics were compared for 76 patients with Down syndrome and 4,733 other patients with newly diagnosed ALL treated on protocols of the Pediatric Oncology Group (POG) and St Jude Children's Research Hospital (SJCRH). Treatment outcome was analyzed for the patients with non-T-cell disease enrolled on a single trial, for whom adequate follow-up data were available. RESULTS Down syndrome patients had lower platelet counts (P &lt; .01) and were less likely to have an anterior mediastinal mass (P &lt; .01) or CNS leukemia (P = .01). They were significantly more likely to have the pre-B immunophenotype (49% v 25.5%, P &lt; .01) and less likely to have T-cell ALL (5.5% v 16%, P = .01). There was a notable absence among patients with Down syndrome of the t(4;11), t(1;19), and t(9;22), which are chromosomal translocations associated with an adverse prognosis in ALL. Treatment outcome did not differ significantly between patients with Down syndrome and the other children with non-T-cell ALL (P = .21); a third of the treatment failures in the former group resulted from treatment-related toxicities. CONCLUSION Children with Down syndrome and ALL had a low frequency of adverse clinicobiologic features at diagnosis. However, these findings did not translate into a superior outcome, apparently because of treatment-related toxicity in this group. Future trials should focus on pharmacokinetics and other strategies to reduce toxicity in these compromised patients.
Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD
Authors: Richard Torres, Heino Velazquez, John J. Chang, Michael J. Levene, Gilbert Moeckel, Gary V. Desir, Robert Safirstein
Journal: Journal of the American Society of Nephrology (2015)

Traditional histologic methods are limited in their ability to detect pathologic changes of CKD, of which cisplatin therapy is an important cause. In addition, poor reproducibility of available methods has limited analysis of the role of fibrosis in CKD. Highly labor-intensive serial sectioning studies have demonstrated that three-dimensional perspective can reveal useful morphologic information on cisplatin-induced CKD. By applying the new technique of multiphoton microscopy (MPM) with clearing to a new mouse model of cisplatin-induced CKD, we obtained detailed morphologic and collagen reconstructions of millimeter-thick renal sections that provided new insights into pathophysiology. Quantitative analysis revealed that a major long-term cisplatin effect is reduction in the number of cuboidal cells of the glomerular capsule, a change we term the "uncapped glomerulus lesion." Glomerulotubular disconnection was confirmed, but connection remnants between damaged tubules and atubular glomeruli were observed. Reductions in normal glomerular capsules corresponded to reductions in GFR. Mild increases in collagen were noted, but the fibrosis was not spatially correlated with atubular glomeruli. Glomerular volume and number remained unaltered with cisplatin exposure, but cortical tubulointerstitial mass decreased. In conclusion, new observations were made possible by using clearing MPM, demonstrating the utility of this technique for studies of renal disease. This technique should prove valuable for further characterizing the evolution of CKD with cisplatin therapy and of other conditions.
Unusual thoracic radiographic findings in children treated for Hodgkin's disease.
Authors: M S Jochelson, N J Tarbell, H J Weinstein
Journal: Journal of Clinical Oncology (1986)

Mantle irradiation is often part of the treatment for Hodgkin's disease. Localized pneumonitis and fibrosis are well-known sequelae of this treatment. We report nine patients with unusual thoracic radiographic findings following treatment for Hodgkin's disease. All nine had mediastinal widening. Seven of these patients received combined modality therapy in which prednisone was given with their MOPP. In these seven patients, an increase in mediastinal width developed at the same time as the radiographic changes of radiation pneumonitis. Two patients developed bilateral infiltrates extending beyond the field of radiation to the lung periphery. In one of these patients, a spontaneous pneumomediastinum developed. One patient underwent mediastinal biopsy that revealed inflammatory changes similar to those seen in radiation pneumonitis. All patients either responded to steroids or had spontaneous regression of radiographic abnormalities supporting the presumed diagnosis of treatment related changes. Recognition of these unusual sequelae of mantle irradiation will aid in differentiating them from infection or tumor and lead to prompt, appropriate treatment.
Expression of Murine Mammary Tumor Virus-Related Antigens in Human Breast Carcinoma (MCF-7) Cells 2
Authors: N.S. Yang, H. D. Soule, C. M. McGrath
Journal: JNCI Journal of the National Cancer Institute (1977)

Tested by the indirect immunofluorescence technique, a human breast carcinoma cell in continuous in vitro cultivation (MCF-7) was found to express antigens cross-reactlve with the murine mammary tumor virus (MuMTV), but not with murine leukemia virus or Mason-Pfizer monkey virus. Antiserum dilution, antiserum absorption, and antiserum blocking experiments showed the cross-reactivity observed in MCF-7 cells to be MuMTV-specific. In long-term passage, only 4–6% of the total population of MCF-7 cells reacted specifically with anti-MuMTV sera. The number of specifically reactive cells could be increased up to 9–14% by treating MCF-7 cells with 10-7 or 10-am progesterone. Neither 5-iododeoxyuridine (IUdR), dexamethasone, nor IUdR plus dexamethasone, potent inducers of MuMTV expression in mouse cells, had any effect on MuMTV cross-reactive antligen expression in MCF-7 cells. Late-passage MCF-7 monolayers were phenotypic mixtures of cells. Small cells (S-cells) comprised 80–90% of the cells, and 10–20% were cells two to three times larger (L-cells). L-cells exclusively reacted with MuMTV antisera and responded to progesterone with augmented antigen levels. L-cells were separated from S-cells by cloning. Again, only L-cells In L-cell clones reacted with MuMTV antisera. The number of L-cell clones could be increased from 15% to about 35% by prolonged treatment of cells in the parent monolayer with IUdR; this resulted in a parallel increase in MuMTV-positive L-cells. However, the segregation of L-cells from S-cells and the increase in the number of L-cells by IUdR treatment did not permanently increase the number of MuMTV-positive cells. MuMTV-positive L-cells converted to MuMTV-negatlve L-cells rapidly during cell division such that the number of MuMTV-positive L-cells per clone was inversely related to clone size (I.e., number of cells per clone). To determine the sequence of events in dimunition of antigen synthesis in MCF-7 cell monolayers, earlier MCF-7 passages were examined. Passages 6–10 of one subllne were 50–60% positive in reactivity with anti-MuMTV sera. Approximately 80% of cells in these passages were L-cells. Within four subsequent passages, the percentage of MuMTV-positive cells diminished from 50–60% to 4–6%. During that time, the cultures remained at least 70% L-cells. Two models of growth dynamics were proposed to account for phenotypic Interconversions of MCF-7 cells during in vitro proliferation.
Targeted Therapy for Breast Cancer Stem Cells by Liposomal Delivery of siRNA against Fibronectin EDB
Authors: Yujin Sun, Hoe Suk Kim, Phei Er Saw, Sangyong Jon, Woo Kyung Moon
Journal: Advanced Healthcare Materials (2015)

Targeted therapy for breast cancer stem cell (BCSC): A novel liposomal system (APTEDB-LS-siRNAEDB) that enables simultaneous targeting and knockdown of extra domain B of fibronectin (EDB-FN) shows potent therapeutic efficacy in the BCSC-derived tumors in vivo.