Lung cancer is notorious for its ability to metastasize, but the pathways regulating lung cancer metastasis are largely unknown. An in vitro system designed to discover factors critical for lung ...cancer cell migration identified brain-derived neurotrophic factor, which stimulates cell migration through activation of tropomyosin-related kinase B (TrkB; also called NTRK2). Knockdown of TrkB in human lung cancer cell lines significantly decreased their migratory and metastatic ability in vitro and in vivo. In an autochthonous lung adenocarcinoma model driven by activated oncogenic Kras and p53 loss, TrkB deficiency significantly reduced metastasis. Hypoxia-inducible factor-1 directly regulated TrkB expression, and, in turn, TrkB activated Akt signaling in metastatic lung cancer cells. Finally, TrkB expression was correlated with metastasis in patient samples, and TrkB was detected more often in tumors that did not have Kras or epidermal growth factor receptor mutations. These studies demonstrate that TrkB is an important therapeutic target in metastatic lung adenocarcinoma.
A large, pedunculated cutaneous mass protruding from the left flank fold and an enlarged left prefemoral lymph node were found on examination of a 3-d-old crossbred Aberdeen Angus heifer. The calf ...was asymptomatic aside from peripheral lymphadenopathy, and the mass, along with the left prefemoral lymph node, was surgically excised. Histologic examination of the mass and the lymph node revealed a homogeneous population of neoplastic cells that stained positively with immunohistochemical stains S100 and melan A, supporting a diagnosis of congenital amelanotic melanoma with nodal metastasis. Two months later, the calf became acutely recumbent and was euthanized after clinical examination revealed widespread metastasis. Gross autopsy revealed widely disseminated metastases that involved vertebral bodies, spinal cord, heart, kidneys, lungs, oral mucosa, multiple lymph nodes, and the marrow cavity of several long bones. Our case serves as a reminder that, although rare, congenital neoplasms occur in bovids and have the potential for aggressive, metastatic behavior.
Testing immunoreactive trypsinogen (IRT) is the first step in cystic fibrosis (CF) newborn screening. While high IRT is associated with CF, some cases are missed. This survey aimed to find factors ...associated with missed CF cases due to IRT levels below program cutoffs. Twenty-nine states responded to a U.S-wide survey and 13 supplied program-related data for low IRT false screen negative cases (CFFN) and CF true screen positive cases (CFTP) for analysis. Rates of missed CF cases and odds ratios were derived for each factor in CFFNs, and two CFFN subgroups, IRT above ("high") and below ("low") the CFFN median (39 ng/mL) compared to CFTPs for this entire sample set. Factors associated with "high" CFFN subgroup were Black race, higher IRT cutoff, fixed IRT cutoff, genotypes without two known CF-causing variants, and meconium ileus. Factors associated with "low" CFFN subgroup were older age at specimen collection, Saturday birth, hotter season of newborn dried blood spot collection, maximum ≥ 3 days laboratories could be closed, preterm birth, and formula feeding newborns. Lowering IRT cutoffs may reduce "high" IRT CFFNs. Addressing hospital and laboratory factors (like training staff in collection of blood spots, using insulated containers during transport and reducing consecutive days screening laboratories are closed) may reduce "low" IRT CFFNs.
Heat-related injury in lambs Sula, Mee Ja M; Winslow, Christine M; Boileau, Melanie J ...
Journal of veterinary diagnostic investigation,
07/2012, Letnik:
24, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The broad spectrum of heat-related injury (HRI) and its associated lesions is well described in the human literature, with rare reports of similar findings in farm animals. In the current case ...series, lesions from 4 of 8 lambs that presented with clinical signs of heat stress are reported. Gross lesions at necropsy consisted of acute renal swelling and pallor in 2 of 4 lambs, muscle pallor in 2 of 4 lambs, and chronic bronchointerstitial pneumonia in each of the 4 lambs. Histological lesions considered heat-related included acute renal tubular necrosis, pigment casts, tubular epithelial regeneration, multifocal myocyte degeneration, necrosis, and dropout with histiocytic influx and regeneration. Chronic, bronchointerstitial pneumonia, present in each lamb, was considered a condition predisposing to HRI. Compatibility between observed lesions and those reported in human beings with injury secondary to elevated body temperatures established a diagnosis of HRI in these animals. Diagnostic pathologists should consider HRI in lambs with histological evidence of renal tubular necrosis and/or rhabdomyolysis and even in cases where the clinical picture is strongly suggestive but lesions are not demonstrable.
Background and purpose
Mutations in the glucocerebrosidase (GBA) gene are known to be a risk factor for Parkinson's disease (PD). Data on clinicopathological correlation are limited. The purpose of ...this study was to determine the clinicopathological findings that might distinguish PD cases with and without mutations in the GBA gene.
Methods
Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to identify autopsied PD cases that did or did not have a GBA gene mutation. Clinical and neuropathological data were compared.
Results
Twelve PD cases had a GBA mutation and 102 did not. The GBA mutation cases died younger (76 vs. 81 years of age) but there was no difference in disease duration or clinical examination findings. No neuropathological differences were found in total or regional semi‐quantitative scores for Lewy‐type synucleinopathy, senile plaques, neurofibrillary tangles, white matter rarefaction or cerebral amyloid angiopathy scores.
Conclusions
In longitudinally assessed, autopsied PD cases, those with GBA mutations had a younger age at death but there was no evidence for clinical or neuropathological differences compared to cases without GBA mutations. Due to the small GBA group size, small differences cannot be excluded.
Clemastine (1 mg) is currently available over-the-counter for the treatment of allergic rhinitis.
To evaluate the efficacy of half the standard dose of clemastine (0.5 mg) in inhibiting the nasal ...response to allergen and the cutaneous response to histamine.
Double-blind, placebo-controlled, crossover study of 20 allergic subjects out of season. The subjects received placebo or clemastine administered one, four, and six hours before the challenges. Filter paper discs were used both to challenge the nasal mucosa with diluent and allergen and collect generated secretions. Sneezes, secretion weights, nasal and ocular symptoms, and albumin levels in nasal secretions were monitored for the nasal challenge. Intradermal skin testing was performed with diluent followed by histamine and the wheal and flare reactions were measured.
There was a significant reduction in the number of sneezes after clemastine administered one, four, and six hours prior to challenge compared with placebo (P < .01). Clemastine administered four and six hours before challenge reduced sneezing significantly more than clemastine administered one hour before challenge (P < .05). Antigen-induced increases in secretion weights and symptoms of rhinorrhea were significantly reduced compared with placebo only when clemastine was administered four and six hours prior to challenge (P < .05). Pretreatment with clemastine had no significant inhibitory effects on other nasal symptoms or on albumin levels in nasal secretions, an objective index of increased vascular permeability. Pretreatment with clemastine did not inhibit the histamine-induced wheal skin reaction but showed a tendency, when administered six hours prior to the intradermal challenge, to reduce the flare reaction induced by the lowest dose of histamine (P = .05).
The data show that clemastine, given at half the usual dose four and six hours prior to allergen challenge, provides relief for sneezing and rhinorrhea and suggests that this dose might be useful in the treatment of allergic rhinitis.
This article describes the effects of cyclosporin A (CsA) on the immunopathological mechanisms operative in psoriasis, a human skin disease. The main focus is the effect of CsA on keratinocytes, T ...cells and antigen-presenting cells, the key players in lesional psoriatic skin. The effect of CsA on other cells, such as neutrophils and endothelial cells, which are important in the maintenance of psoriasis, are also discussed.
What is already known about this topic? A global monkeypox outbreak is currently primarily affecting gay, bisexual, and other men who have sex with men. What is added by this report? In a recent ...survey of gay, bisexual, and other men who have sex with men, approximately one half reported reducing their number of sex partners, one-time sexual encounters, and use of dating apps because of the monkeypox outbreak. Receipt of vaccine to protect against monkeypox varied by race, ethnicity, and geography. What are the implications for public health practice? It is essential that public health programs continue to deliver tailored, respectful harm reduction messages that do not create stigma to diverse communities of men who have sex with men. Vaccine programs should prioritize efforts to maximize equitable access.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Background The 5-year overall survival rate of lung cancer patients is approximately 15%. Most patients are diagnosed with advanced-stage disease and have shorter survival rates than patients with ...early-stage disease. Although screening for lung cancer has the potential to increase early diagnosis, it has not been shown to reduce lung cancer mortality rates. In 1993, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was initiated specifically to determine whether screening would reduce mortality rates from PLCO cancers. Methods A total of 77 464 participants, aged 55–74 years, were randomly assigned to the intervention arm of the PLCO Cancer Screening Trial between November 8, 1993, and July 2, 2001. Participants received a baseline chest radiograph (CXR), followed by three annual single-view CXRs at the 10 US screening centers. Cancers were classified as screen detected and nonscreen detected (interval or never screened) and according to tumor histology. The positivity rates of screen-detected cancers and positive predictive values (PPVs) were calculated. Because 51.6% of the participants were current or former smokers, logistic regression analysis was performed to control for smoking status. All statistical tests were two-sided. Results Compliance with screening decreased from 86.6% at baseline to 78.9% at the last screening. Overall positivity rates were 8.9% at baseline and 6.6%–7.1% at subsequent screenings; positivity rates increased modestly with smoking risk categories (Ptrend < .001). The PPVs for all participants were 2.0% at baseline and 1.1%, 1.5%, and 2.4% at years 1, 2, and 3, respectively; PPVs in current smokers were 5.9% at baseline and 3.3%, 4.2%, and 5.6% at years 1, 2, and 3, respectively. A total of 564 lung cancers were diagnosed, of which 306 (54%) were screen-detected cancers and 87% were non–small cell lung cancers. Among non–small cell lung cancers, 59.6% of screen-detected cancers and 33.3% of interval cancers were early (I–II) stage. Conclusions The PLCO Cancer Screening Trial demonstrated the ability to recruit, retain, and screen a large population over multiple years at multiple centers. A higher proportion of screen-detected lung cancers were early stage, but a conclusion on the effectiveness of CXR screening must await final PLCO results, which are anticipated at the end of 2015.
SRI 62-834, an analog of the antitumor agent ET-18-OCH3 in which the oxygen atom at carbon atom 2 has been incorporated into a five-membered heterocycle, has been prepared and evaluated as an ...antitumor agent. The compound exhibited good cytotoxicity in vitro against a variety of tumor cell lines and was as effective as ET-18-OCH3 given orally in the mouse Meth A sarcoma model. SRI 62-834 was shown to be an inhibitor of platelet-derived growth factor (PDGF), possibly at the receptor level, and platelet-activating factor (PAF) at the receptor level.
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