Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute promyelocytic leukaemia (M3): Relapse with acute myeloblastic leukaemia (M2) and dic(5;17) (q11; p11)

Secondary leukaemia following treatment of M3 acute promyelocytic leukaemia (APL) is a rare event. We describe a patient in remission following chemotherapy for APL who relapsed with M2 acute non‐lymphoblastic leukaemia (ANLL). The original t(15;17) (q22; q21) chromosome translocation was lost and replaced by a clone containing a dic(5;17) (q11; p11) abnormality. Southern genomic analysis demonstrated re‐arrangements of the retinoic acid receptor α (RARα) and PML genes in the APL blasts at presentation but not in the M2 ANLL marrow at relapse. The significance of unbalanced 5;17 translocations as markers for therapy‐related secondary leukaemia is discussed. ©1995 Wiley‐Liss, Inc.
Mycobacterium tuberculosis infection causes different levels of apoptosis and necrosis in human macrophages and alveolar epithelial cells

Mycobacterium tuberculosis interacts with macrophages and epithelial cells in the alveolar space of the lung, where it is able to invade and replicate in both cell types. M. tuberculosis‐associated cytotoxicity to these cells has been well documented, but the mechanisms of host cell death are not well understood. We examined the induction of apoptosis and necrosis of human macrophages (U937) and type II alveolar epithelial cells (A549) by virulent (H37Rv) and attenuated (H37Ra) M. tuberculosis strains. Apoptosis was determined by both enzyme‐linked immunosorbent assay (ELISA) and TdT‐mediated dUTP nick end labelling (TUNEL) assay , whereas necrosis was evaluated by the release of lactate dehydrogenase (LDH). Both virulent and attenuated M. tuberculosis induced apoptosis in macrophages; however, the attenuated strain resulted in significantly more apoptosis than the virulent strain after 5 days of infection. In contrast, cytotoxicity of alveolar cells was the result of necrosis, but not apoptosis. Although infection with M. tuberculosis strains resulted in apoptosis of 14% of the cells on the monolayer, cell death associated with necrosis was observed in 59% of alveolar epithelial cells after 5 days of infection. Infection with M. tuberculosis suppressed apoptosis of alveolar epithelial cells induced by the kinase inhibitor, staurosporine. Because our findings suggest that M. tuberculosis can modulate the apoptotic response of macrophages and epithelial cells, we carried out an apoptosis pathway‐specific cDNA microarray analysis of human macrophages and alveolar epithelial cells. Whereas the inhibitors of apoptosis, bcl‐2 and Rb, were upregulated over 2.5‐fold in infected (48 h) alveolar epithelial cells, the proapoptotic genes, bad and bax, were downregulated. The opposite was observed when U937 macrophages were infected with M. tuberculosis. Upon infection of alveolar epithelial cells with M. tuberculosis, the generation of apoptosis, as determined by the expression of caspase‐1, caspase‐3 and caspase‐10, was inhibited. Inhibition of replication of intracellular bacteria resulted in an increase in apoptosis in both cell types. Our results showed that the differential induction of apoptosis between macrophages and alveolar epithelial cells represents specific strategies of M. tuberculosis for survival in the host.
Variation of blood T lymphocyte subgroups in patients with non- small cell lung cancer.

OBJECTIVES To study variation in T lymphocyte subgoups and its clinical significance in non-small cell lung cancer (NSCLC). METHODS Levels of CD3+ , CD4+ , CD8+ , CD4+/CD8+, NK and Treg cells in peripheral blood of NSCLC cases and healthy adults were determined by flow cytometry. RESULTS CD3+ , CD4+ and CD4+/CD8+ ratio and NK cells in NSCLCs were decreased significantly in comparison with the control group (P < 0.01), and decreased with increase in the clinical stage of NSCLC, while CD8+ cells demonstrated no significant change (P > 0.05). Treg cells were significantly more frequent than in the control group (P < 0.01), and increased with the clinical stage of NSCLC. CONCLUSION The cellular immune function of the NSCLC patients is lowered. It is important to detect change of T lymphocyte subgroups by flow cytometry for the diagnosis, treatment and prognostic assessment of NSCLC patients.
Drug inhibition of Gly-Sar uptake and hPepT1 localization using hPepT1-GFP fusion protein

An hPepT1-GFP fusion construct was made to study drug inhibition of dipeptide uptake and apical, basolateral, or subcellular hPepT1 localization. The hPepT1 stop codon was mutated by polymerase chain reaction and was subsequently cloned into the pEGFP-N1 vector. The hPepT1-GFP fusion construct was then transfected into Caco-2 and HeLa cells, and drug inhibition was studied by inhibiting 3H-Gly-Sar uptake. Western blot analysis was used to determine hPepT1-GFP expression levels and confocal microscopy was used to examine the localization. Both anti-hPepT1 antibody and anti-GFP antibody recognized a 120kd hPepT1-GFP fusion protein in the transfected cells. The 3H-Gly-Sar uptake in transfected HeLa cells was enhanced more than 20 times compared with the control. Valacyclovir (5 mmol/L) was able to completely inhibit 3H-Gly-Sar uptake in these transfected cells. Confocal microscopy showed that the hPepT1-GFP mainly localized in the Caco-2 cell apical membrane, but was present throughout the entire HeLa cell membranes. The hPepT1-GFP fusion protein was not found in either early endosome or lysosome of Caco-2 cells under normal conditions; however, it was detected in some subsets of lysosomes and early endosomes in phorbol 12-myristate 13-acetate (PMA)-treated Caco-2 cells.
Is There a Role for Palliative Care in Progressive Pediatric Neuromuscular Diseases? The Answer is “Yes”!

The consequences of prolongation of survival can be oversimplified, for example, by equating technologically prolonged survival with indefinitely prolonged high quality of life. When this oversimplified view is embraced, the prognosis of ultimately fatal diseases like DMD may be viewed with unrealistic optimism and palliative care may seem irrelevant or misguided. However, we have shown that the sequelae of prolonged survival are complex. For example, NPPV does not protect prolonged survivors of progressive NMDs from potentially debilitating medical complications that can cause elevated burden of disease, high burden of care, and the potential for impaired quality of life. Also, the sequelae of prolonged survival can negatively affect a wide variety of stakeholders, including patients and their families, medical professionals, and society. It is our view that, when the implications of prolonged survival are examined carefully, their complexity is revealed, and the potential for palliative care to provide support and to relieve suffering in prolonged survivors of progressive NMDs becomes apparent. Thus, we advocate development of an integrative care model for patients with progressive NMDs, blending technological therapies with adoption of palliative strategies as patients approach end of life.
Cumulative trauma and current posttraumatic stress disorder status in general population and inmate samples.

OBJECTIVE This research was undertaken to examine the role between cumulative exposure to different types of traumatic events and posttraumatic stress disorder (PTSD) status in general population and prison samples. METHODS Two archival datasets were examined: the standardization sample for the Detailed Assessment of Posttraumatic States (DAPS; Briere, 2001), and data from a study on trauma and posttraumatic sequelae among inmates and others. RESULTS PTSD was found in 4% of the general population sample and 48% of the prison sample. Trauma exposure was very common among prisoners, including a 70% rate of childhood sexual abuse for women and a 50% rate for men. Lifetime number of different types of trauma was associated with PTSD in both the general population and prison samples, even when controlling for the effects of sexual trauma. Cumulative interpersonal trauma predicted PTSD, whereas cumulative noninterpersonal trauma did not. In the general population sample, participants who had only 1 type of trauma exposure had a 0% likelihood of current PTSD, whereas those with 6 or more other trauma types had a 12% likelihood. In the prison sample, those with only 1 type of trauma exposure had a 17% percent likelihood of current PTSD, whereas those exposed to 6 or more other trauma types had a 64% chance of PTSD. CONCLUSION Cumulative trauma predicts current PTSD in both general population and prison samples, even after controlling for sexual trauma. PTSD appears to develop generally as a function of exposure to multiple types of interpersonal trauma, as opposed to a single traumatic event. (PsycINFO Database Record
CD44s as a surrogate marker for distinguishing intraductal papilloma from papillary carcinoma of the breast.

BACKGROUND: It has been shown that CD44 variants are differentially expressed in normal and neoplastic breast tissues. The diagnostic value of these markers in distinguishing benign from malignant breast lesions has not been well examined. AIMS: To evaluate the diagnostic value of CD44s in distinguishing between intraductal papillomas and papillary carcinomas of the breast, which may be difficult morphologically. METHODS: Expression of CD44s detected by immunohistochemistry was studied in a series of intraductal papillomas (11) and papillary carcinomas (10). The normal breast tissues surrounding the lesions of these cases served as a control. The number of CD44s positive epithelial cells was scored and categorised as < 10%, 10-70%, or > 70%. RESULTS: Normal breast epithelial cells and all intraductal papillomas (11 of 11) expressed CD44s in a high proportion of cells (> 70%). In contrast, the majority of papillary carcinoma cases (eight of 10) expressed this marker in < 10% of the cells. In the remaining two papillary carcinoma cases, positivity was seen in more than 10% but still less than 70% of the cells. CONCLUSIONS: CD44s detection by immunohistochemistry is useful in distinguishing intraductal papillomas from papillary carcinomas of the breast.
Early Treatment of Transient Focal Cerebral Ischemia with Bovine PEGylated Carboxy Hemoglobin Transfusion

Abstract: The effect of transfusion of PEGylated hemoglobin (PEG-Hb) was evaluated in anesthetized rats subjected to 2 hours of focal cerebral ischemia and 1 day of reperfusion. PEG-Hb was stored in the carboxy state (PEG-COHb) to reduce autooxidation and increase the shelf life. Transfusion of 10 ml/kg of PEG-COHb at 20 minutes of ischemia did not alter arterial blood pressure or increase red cell flux in the ischemic core. Plasma hemoglobin increased to only 0.6 g/dL, yet infarct volume was markedly decreased and neurological deficits were improved. We conclude that early topload transfusion of PEG-COHb protects the brain from ischemic stroke.
Class I Myosins Have Overlapping and Specialized Functions in Left-Right Asymmetric Development in Drosophila

The class I myosin genes are conserved in diverse organisms, and their gene products are involved in actin dynamics, endocytosis, and signal transduction. Drosophila melanogaster has three class I myosin genes, Myosin 31DF (Myo31DF), Myosin 61F (Myo61F), and Myosin 95E (Myo95E). Myo31DF, Myo61F, and Myo95E belong to the Myosin ID, Myosin IC, and Myosin IB families, respectively. Previous loss-of-function analyses of Myo31DF and Myo61F revealed important roles in left–right (LR) asymmetric development and enterocyte maintenance, respectively. However, it was difficult to elucidate their roles in vivo, because of potential redundant activities. Here we generated class I myosin double and triple mutants to address this issue. We found that the triple mutant was viable and fertile, indicating that all three class I myosins were dispensable for survival. A loss-of-function analysis revealed further that Myo31DF and Myo61F, but not Myo95E, had redundant functions in promoting the dextral LR asymmetric development of the male genitalia. Myo61F overexpression is known to antagonize the dextral activity of Myo31DF in various Drosophila organs. Thus, the LR-reversing activity of overexpressed Myo61F may not reflect its physiological function. The endogenous activity of Myo61F in promoting dextral LR asymmetric development was observed in the male genitalia, but not the embryonic gut, another LR asymmetric organ. Thus, Myo61F and Myo31DF, but not Myo95E, play tissue-specific, redundant roles in LR asymmetric development. Our studies also revealed differential colocalization of the class I myosins with filamentous (F)-actin in the brush border of intestinal enterocytes.
PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES

Abstract Aspergillosis is a common respiratory fungal disease in African penguins (Spheniscus demersus) under managed care, and treatment failures with itraconazole due to drug resistance are increasingly common, leading to recent use of voriconazole. Empirical dosing with voriconazole based on other avian studies has resulted in adverse clinical drug effects in penguins. The objective of this study was to determine oral voriconazole pharmacokinetics (PK) in African penguins (n = 18). Single and once daily multiple oral doses of 5 mg/kg voriconazole were evaluated with a 4-mo washout period between trials. Plasma voriconazole concentrations were determined via high-performance liquid chromatography. Data was modeled using 3-compartamental population methodologies that supported first-order elimination. Observed mean peak concentration (1.89 μg/ml) after single dosing PK analysis was determined within the first hour following voriconazole administration. In the multiple-dose trial average plasma voriconazole concentrations were significantly higher on days 4 and 7 as compared with day 2. The mean estimates for volume of distribution (V/F) and clearance (Cl/F) for the multiple-dose study were 3.34 L and 0.18 L/hr, respectively. Monte Carlo simulations determined the median area under the curve (AUC0–24) at 84 hr was 37.7 μg·h/ml. As this assessment was comparable with the average AUC in humans receiving the recommended human oral dosage 200 mg b.i. d. , it suggests that 5 mg/kg p.o. s.i. d. could be a safe and effective regimen in African penguins for treatment of aspergillosis. However, due to potential drug accumulation and subsequent toxicity, therapeutic drug monitoring with dosage adjustments is recommended to individualize dosing.
Assessment of the role of gamma-toxin in experimental endophthalmitis using a hlg-deficient mutant of Staphylococcus aureus.

Purified gamma-toxin is known to have a proinflammatory effect in the rabbit vitreous humor. To assess the biological role of the gamma-toxin, when expressed in vivo by Staphylococcus aureus strain Newman, the vitreous humor of rabbit eye was used as an infection model. A gamma-toxin-deficient mutant of strain Newman was constructed by allelic replacement. S. aureus Newman wild-type, its hlg-deficient derivative strain (N65) and the strain N65 complemented with the wild-type hlg+ gene were injected into the vitreous humor of rabbit eye. All three strains produced a strong proinflammatory effect in the eye conjunctiva, posterior and anterior chambers, suggesting a role for another unidentified proinflammatory component of strain Newman distinct from the gamma-toxin. These components are not the leucocidin of Panton-Valentine, beta-toxin or alpha-toxin which are not produced by this strain. Only the hlg-deficient mutant lacked the ability to cause inflammation in the eyelid, whereas the two Hlg-producing strains gave strong inflammation. These data suggest that in vivo, strain Newman produces as yet unidentified proinflammatory molecules and that the in vivo-produced HlgA, HlgB and HlgC molecules expressed by the gamma-toxin locus, contribute in part to the inflammatory process observed in vivo in the rabbit eye.
Motivational processes and autonomic responsivity in Asperger's disorder: Evidence from the Iowa Gambling Task

Asperger's disorder (ASP), like other autism spectrum disorders, is associated with altered responsiveness to social stimuli. This study investigated learning and responsiveness to nonsocial, but motivational, stimuli in ASP. We examined choice behavior and galvanic skin conductance responses (SCRs) during the Iowa Gambling Task (IGT; Bechara et al., 1994) in 15 adolescents and young adults with ASP and 14 comparison subjects. We examined aspects of learning, attention to wins and losses, and response style with a formal cognitive model, the Expectancy–Valence Learning model (Busemeyer & Stout, 2002). The ASP group did not differ from the comparison group in proportions of selections from advantageous decks. However, ASP participants showed a distinct pattern of selection characterized by frequent shifts between the four IGT decks, whereas comparison participants developed clear deck preferences. SCR results showed some evidence of reduced responsiveness in the ASP group during the IGT. Results from the cognitive model indicated that, in contrast to the comparison group, the ASP group's selections were less consistent with the motivational significance they assigned to decks. Findings are discussed in the context of the neurobiological substrates associated with IGT performance (JINS, 2006, 12, 668–676.)
Utilization of a hospital for treatment of pediatric dental emergencies.

PURPOSE The purpose of this study was to investigate dental emergencies treated at a hospital clinic and emergency department (ED) to: (1) analyze emergency types; (2) determine reasons for seeking hospital care; and (3) examine trends compared to previous studies from this institution. METHODS Records of 2,683 emergencies from 1995 to 2003 were reviewed. Demographics, reason for seeking care, and treatment details were analyzed overall by emergency type and for subgroups of patients with severe early childhood caries (S-ECC) and patients referred from other EDs. RESULTS Emergencies were: 51% trauma, 40% caries, and 9% "other" emergencies unrelated to trauma or caries. Common patient characteristics were: (1) young age; (2) non-Caucasian ethnicity; (3) Medicaid as payer; (4) no dentist; and (5) proximity to the hospital. Caries emergencies increased significantly over the study period (P = .008), and 22% had S-ECC. Patients referred from other EDs were: 11% of trauma patients who commonly required sutures and/or extractions; and 3% of caries patients, 82% with extraoral swelling. CONCLUSIONS Characteristics of patients seeking hospital care for dental emergencies were: (1) young age; (2) non-Caucasian ethnicity; (3) Medicaid as payer; (4) no dentist; and (5) proximity to CHRMC. Use differed by ethnic groups: Caucasians presented mostly for trauma; African Americans presented equally for caries and trauma; and Hispanics and Asians presented primarily for caries. Access to care, caries, and severe early childhood caries remain significant problems despite multiple programs targeting children's' oral health in Washington State.
CERES–Maize Model for Determining the Optimum Planting Dates of Early Maturing Maize Varieties in Northern Nigeria

Field trials were carried out in the Sudan Savannah of Nigeria to assess the usefulness of CERES–maize crop model as a decision support tool for optimizing maize production through manipulation of plant dates. The calibration experiments comprised of 20 maize varieties planted during the dry and rainy seasons of 2014 and 2015 at Bayero University Kano and Audu Bako College of Agriculture Dambatta. The trials for model evaluation were conducted in 16 different farmer fields across the Sudan (Bunkure and Garun—Mallam) and Northern Guinea (Tudun-Wada and Lere) Savannas using two of the calibrated varieties under four different sowing dates. The model accurately predicted grain yield, harvest index, and biomass of both varieties with low RMSE-values (below 5% of mean), high d-index (above 0.8), and high r-square (above 0.9) for the calibration trials. The time series data (tops weight, stem and leaf dry weights) were also predicted with high accuracy (% RMSEn above 70%, d-index above 0.88). Similar results were also observed for the evaluation trials, where all variables were simulated with high accuracies. Estimation efficiencies (EF)-values above 0.8 were observed for all the evaluation parameters. Seasonal and sensitivity analyses on Typic Plinthiustalfs and Plinthic Kanhaplustults in the Sudan and Northern Guinea Savannas were conducted. Results showed that planting extra early maize varieties in late July and early maize in mid-June leads to production of highest grain yields in the Sudan Savanna. In the Northern Guinea Savanna planting extra-early maize in mid-July and early maize in late July produced the highest grain yields. Delaying planting in both Agro-ecologies until mid-August leads to lower yields. Delaying planting to mid-August led to grain yield reduction of 39.2% for extra early maize and 74.4% for early maize in the Sudan Savanna. In the Northern Guinea Savanna however, delaying planting to mid-August resulted in yield reduction of 66.9 and 94.3% for extra-early and early maize, respectively.
Bone morphogenetic protein‐7 in focus: A member of the transforming growth factor‐β superfamily is implicated in the maintenance of liver health

Bone morphogenic protein-7 (BMP-7) is a key protein involved in liver organogenesis and development. The physiological circulating concentration of BMP-7 is between 100 and 300 pg/ml. BMP-7 expression is absent in the liver, but the receptors for BMP-7 are present on adult hepatocytes. Therefore, we hypothesized that BMP-7 might function as an endogenous regulator of adult hepatocyte proliferation and liver homeostasis. Here, we demonstrate that neutralization of circulating endogenous BMP-7 results in significantly impaired regeneration of the liver after partial hepatectomy. Therapeutic administration of recombinant human BMP-7 (rhBMP-7) significantly enhances liver regeneration associated with accelerated improvement of liver function. Collectively, our results argue for the role of BMP-7 as a kidneyand bone-produced endogenous regulator of hepatocyte health. Kinoshita K, Iimuro Y, Otogawa K, Saika S, Inagaki Y, Nakajima Y, et al. Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats. Gut; November 24, 2006, Epub ahead of print.