Miracle-dz/UniFAR-FTUs huggingface dataset:
Recovery of function after lesions in the superior temporal sulcus in the monkey.

1. Ibotenic acid lesions in the monkey's middle temporal area (MT) and the medial superior temporal area (MST) in the superior temporal sulcus (STS) have previously been shown to produce a deficit in initiation of smooth-pursuit eye movements to moving visual targets. The deficits, however, recovery within a few days. In the present experiments we investigated the factors that influence that recovery. 2. We tested two aspects of the monkey's ability to use motion information to acquire moving targets. We used eye-position error as a measure of the monkey's ability to make accurate initial saccades to the moving target. We measured eye speed within the first 100 ms after the saccade to evaluate the monkey's initial smooth pursuit. 3. We determined that pursuit recovery was not dependent specifically on the use of neurotoxic lesions. Although the rate of recovery was slightly altered by replacing the usual neurotoxin (ibotenic acid) with another neurotoxin [alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] or with an electrolytic lesion, pursuit recovery still occurred within a period of days to weeks. 4. There was a relationship between the size and location of the lesion and the recovery time. The time to recovery for eye-position error and initial eye speed increased with the fraction of MT removed. Whether the rate of recovery and size of lesions within regions on the anterior bank were related was unresolved. 5. We found that a large AMPA lesion within the STS that removed all of MT and nearly all of MST drastically altered the rate of recovery. Recovery was incomplete more than 7 mo after the lesion. Even with this lesion, however, the monkey's ability to use motion information for pursuit was not completely eliminated. 6. The large lesion also included parts of areas V1, V2, V3, and V4, but analysis of the visual fields associated with this lesion indicated that these areas probably did not have a substantial effect on recovery. 7. We tested whether visual motion experience of the monkey after a lesion was necessary for recovery by limiting the monkey's experience either by using a mask or by using 4-Hz stroboscopic illumination. In one monkey the eye-position error component of pursuit was prolonged to greater than 2 wk, but recovery of eye speed was not. Reduced motion experience had little effect on recovery in the other two monkeys. These results suggest that such visual motion experience is not necessary for the recovery of pursuit. (ABSTRACT TRUNCATED AT 400 WORDS)
Lymphoma cells contribute to the augmentation of plasma sL-selectins in the serum of lymphoma-bearing mice

Like many integral membrane glycoproteins, the extracellular domain of L-selectin undergoes rapid shedding, which occurs on both resting and activated host leucocytes. Incubating normal or transformed leukocytes with phorbol esters can also artificially induce shedding of L-selectin, providing multiple possibilities for the source of soluble forms of L-selectin found in the serum of patients with hematological malignancies. Here, using genetically engineered L-selectin-deficient mouse models, we have measured the release of soluble circulating forms of L-selectin in the serum of lymphoma-bearing mice. We found that L-selectin-deficient lymphoma cells could not induce an elevation of circulating soluble forms of L-selectin in normal mice, as compared to lymphoma cells expressing L-selectin. Moreover, soluble forms of L-selectin were detected in the serum in mice bearing lymphoma induced by injection of T lymphoma cells expressing L-selectins. Interestingly, we also found that lymphoma cells that are unable to shed L-selectin in vitro following exposure to phorbol ester can generate soluble forms of serum L-selectin in vivo. Taken together, these results indicate that lymphoma cells are the major contributors to levels of soluble forms of L-selectins in lymphoma-bearing mice.
Predictors of Mortality in a Cohort of HIV-1-Infected Adults in Rural Africa

Background:CD4 cell count and plasma HIV RNA level are used to monitor HIV-infected patients in high-income countries, but the applicability in an African context with frequent concomitant infections has only been studied sparsely. Moreover, alternative inexpensive markers are needed in the attempts to roll out antiretroviral treatment in the region. We explored the prognostic strengths of classic and alternative progression markers in this study set in rural Zimbabwe. Methods:We followed 196 treatment-naive HIV-1-infected patients from the Mupfure Schistosomiasis and HIV Cohort, Zimbabwe. CD4 cell count, HIV RNA level, hemoglobin (HB), total lymphocyte count (TLC), body mass index, clinical staging (Centers for Disease Control and Prevention [CDC] classification), and self-reported level of function (Karnofsky Performance Scale score) were assessed at baseline; participants were followed until death or last follow-up (3-4.3 years). Results:All parameters except TLC predicted survival in univariate Cox models. HIV RNA level (P = 0.001), HB (P = 0.018), CD4 cell count (P = 0.047), and CDC category C (P = 0.007) remained significant in multivariate analysis. Conclusions:We found HIV RNA level and CD4 cell count to predict mortality with prognostic capabilities similar to findings from high-income countries. HB and clinical staging were strong independent predictors and might be considered candidates for alternative HIV progression markers.
Methods for estimation of bone marrow plasma cell involvement in myeloma: Predictive value for response and survival in patients undergoing autologous stem cell transplantation

In myeloma, the bone marrow plasma cell percentage (BMPC%) is usually estimated independently on the aspirate, core biopsy, and plasma cell labeling index (PCLI) samples. This study was done to determine which of the 3 individual estimates correlates best with complete response (CR) and survival. Seventy‐five consecutive patients who underwent SCT for relapsed myeloma were studied. The median BMPC% on the marrow aspirate, core biopsy, and PCLI studies were 20, 25, and 20, respectively. There was a significant correlation between the three methods, ρ > 0.65, P < 0.001. However, in 8% of patients the BMPC% was different by an absolute value of 50% between methods. No individual method was predictive for CR. However, the highest estimate of the BMPC% among the three methods was a significant predictor of CR (P = 0.02). Survival following SCT was longer among patients with a low BMPC% (≤60) by the PCLI method compared to those with higher values, median survival 23 versus 7 months, respectively, P = 0.02. PFS was also different, with survival times of 11 and 5 months, respectively, P = 0.003. Similar results were obtained when the highest estimate of the BMPC% was used in survival analysis (P = 0.02 and 0.004, respectively). Statistical significance was lower when the BMPC% on the aspirate or biopsy used in survival analysis. Compared to any individual method of estimating BMPC%, the highest estimate of the BMPC% is the best predictor of CR in myeloma. It is also prognostic for poor survival and PFS following SCT for myeloma. We recommend that all three methods of estimating BMPC% be routinely performed and that the highest value be used for prognostic purposes. Am. J. Hematol. 68:269–275, 2001. © 2001 Wiley‐Liss, Inc.
The use of special stains in liver biopsy interpretation: Implications for the management of liver disease in Nigeria.

CONTEXT The evaluation of a liver biopsy requires the use of stains other than routine hematoxylin and eosin (H and E) to highlight many important features. AIMS Most Nigerian Histopathology Departments do not routinely perform special stains (personal communication by authors). This study aims to re-evaluate a set of liver biopsies which has been diagnosed solely on H and E stains by performing a standard set of special stains on them. SETTINGS AND DESIGN This is a retrospective analysis. MATERIALS AND METHODS The formalin fixed paraffin embedded blocks of liver biopsies reported in two histopathology laboratories between 2008 and 2013 were retrieved. These were stained with H and E and the following standard special stains for liver tissue histology - Perl's Prussian blue, reticulin, Sirius red, Shikata orcein, and periodic acid-Schiff with diastase. The stained slides were re-analyzed. STATISTICAL ANALYSIS USED No formal statistical analysis was performed, but results are summarized and tabulated by summary statistics, where appropriate. RESULTS Seventy-four liver biopsy paraffin blocks were received in the laboratories. Fifty-three (71.6%) were suitable for analysis out of which 51 (68.9%) had their clinical details retrievable. In 29 cases (56.9%), Perl's stain was positive for iron pigment within the hepatocytes with 17 (58.6%) of these being Grade 1, 7 (24.1%) Grade 2, and 5 (17.2%) Grade 3. Shikata orcein revealed hepatitis B viral surface antigen in 15 (29.4%) of the cases while copper-associated protein was demonstrable in 6 (11.8%) of the cases. The discovery of stainable iron implies some degree of disturbance of iron metabolism, and a Grade 3 stainable iron requires investigation for genetic hemochromatosis. The demonstration of copper-associated proteins suggests biliary disease in a noncirrhotic liver which also requires further investigation. CONCLUSION This study confirms the need to routinely perform special stains in reporting liver biopsies to fully investigate and manage patients and their relatives.
Early exercise after experimental myocardial infarction: effect on left ventricular remodeling

BackgroundThe effect of exercise on left ventricular remodeling after myocardial infarction is unclear. The purpose of this investigation was to test whether exercise undertaken during the healing phase of an acute myocardial infarction has an adverse effect on left ventricular remodeling. MethodsBefore surgery, rats (n = 94) were allocated randomly to one of four groups: 1) infarct, swimming exercise; 2) infarct, no exercise; 3) sham operation, swimming exercise; 4) sham operation, no exercise. Beginning 1 week after infarction or sham operation, the rats in the exercise groups swam twice daily for 2 weeks. After a deconditioning period of 5 days, the rats were re-anesthetized, hemodynamic measurements were made, and the hearts were fixed for morphometric analysis. ResultsSwimming exercise had no effect on remodeling of infarcted myocardium. Rats with infarcts in the swimming and no exercise groups had similar infarct thicknesses (1.1 ± 0.2 mm and 0.8 ± 0.2 mm respectively; NS), and similar degrees of infarct expansion (expansion index 1.2 ± 0.3 and 1.4 ± 0.3 respectively; NS). Swimming exercise also had no effect on remodeling of non-infarcted myocardium. Left ventricular volumes and pressure–volume relationships were similar in exercised and non-exercised infarcted rats. ConclusionIn rats, 2 weeks of swimming exercise, started 1 week after acute experimental myocardial infarction and followed by 5 days of deconditioning, does not have an adverse effect on left ventricular remodeling.
Staff lens doses in interventional urology. A comparison with interventional radiology, cardiology and vascular surgery values

The purpose of this work is to evaluate radiation doses to the lens of urologists during interventional procedures and to compare them with values measured during interventional radiology, cardiology and vascular surgery. The measurements were carried out in a surgical theatre using a mobile C-arm system and electronic occupational dosimeters (worn over the lead apron). Patient and staff dose measurements were collected in a sample of 34 urology interventions (nephrolithotomies). The same dosimetry system was used in other medical specialties for comparison purposes. Median and 3rd quartile values for urology procedures were: patient doses 30 and 40 Gy cm2; personal dose equivalent Hp(10) over the apron (μSv/procedure): 393 and 848 (for urologists); 21 and 39 (for nurses). Median values of over apron dose per procedure for urologists resulted 18.7 times higher than those measured for radiologists and cardiologists working with proper protection (using ceiling suspended screens) in catheterisation laboratories, and 4.2 times higher than the values measured for vascular surgeons at the same hospital. Comparison with passive dosimeters worn near the eyes suggests that dosimeters worn over the apron could be a reasonable conservative estimate for ocular doses for interventional urology. Authors recommend that at least the main surgeon uses protective eyewear during interventional urology procedures.
H-ras activation in benign and self-regressing skin tumors (keratoacanthomas) in both humans and an animal model system

The involvement of the ras oncogenes in tumorigenesis was investigated in keratoacanthomas, which are benign and self-regressing skin tumors, both in humans and in a corresponding animal model system. Keratoacanthomas were induced on rabbit ears by repeated applications of 7,12-dimethylbenz(a)anthracene. About 60% of the tumor DNAs produced transformed foci after transfection into NIH 3T3 cells, and in all of them the transforming gene was identified as H-ras by Southern and Northern (RNA) hybridization. Immunoprecipitation experiments suggested that the transforming rabbit H-ras protein carried a mutation in codon 61. In addition, an activated H-ras gene was detected in a human keratoacanthoma by using a nude mouse tumorigenesis assay after transfection of tumor DNA into NIH 3T3 cells. This is the first report of ras activation in a benign human tumor. The transforming human H-ras gene showed a point mutation in codon 61 that would result in leucine instead of the glutamine present in the normal gene product. The finding of ras activation in tumors that are not only benign but also self-regressing indicates that activated ras genes are not sufficient to maintain a neoplastic phenotype, although they likely play a role in early stages of tumorigenesis.
Effect of age on the pharmacokinetics of duloxetine in women.

AIMS The effect of age on duloxetine pharmacokinetics was evaluated in healthy volunteers and in patients with urinary incontinence. METHODS Twenty-four healthy subjects (12 women 65-77 years, and 12 women 32-50 years) were given a single 40-mg oral dose of duloxetine in Study 1. Plasma concentration-time data were analysed by noncompartmental pharmacokinetic methods. Sparse plasma samples were obtained from patients with urinary incontinence treated in two phase II studies: 70 women (24-77 years) who received duloxetine 20 mg day(-1), 30 mg day(-1), or 40 mg day(-1) in Study 2A and 128 women (28-64 years) who received duloxetine 20 mg day(-1), 40 mg day(-1), or 80 mg day(-1) in Study 2B. Based upon the combined data, a model was developed to characterize population pharmacokinetics of duloxetine using the nonlinear mixed-effects modelling program (NONMEM). RESULTS In Study 1, the elderly (> or = 65 years) exhibited a statistically significant slower elimination rate constant lambdaz compared with younger subjects [elderly-younger difference = -0.022 h(-1)[95% confidence interval (CI) -0.036, -0.008]]. However, no statistically significant differences in either CL/F [elderly-younger difference = -17.4 l h(-1) (95% CI -41.1, 6.23)] or V/F [elderly-younger difference = 115.9 l (95% CI -168.6, 400.4)] were observed. The population pharmacokinetic analysis of Studies 2A and 2B revealed that the CL/F of duloxetine decreased with increasing age. Despite statistical significance, the age effect only accounted for 3% of the interindividual variability in CL/F and unexplained sources of the variation in clearance were still substantial (> 50%). Adverse events were generally mild to moderate, and the incidence of adverse events was generally similar in elderly and non-elderly participants in these studies. CONCLUSIONS Whereas the results suggest that age has an effect on duloxetine pharmacokinetics, primarily reflected as a slower lambdaz in the elderly, the magnitude of mean changes in CL/F, or V/F was small relative to the large interindividual variation in pharmacokinetics. Elderly participants had a safety profile of duloxetine comparable to their younger counterparts. Specific dose recommendations for duloxetine in the elderly are not warranted.
The importance of serum serotonin levels in the measurement of radiation-induced bystander cell death in HaCaT cells

Abstract Purpose: The aim of this study was to investigate the importance of serum serotonin levels in the measurement of bystander cell death. The study was undertaken as part of an intercomparison exercise involving seven European laboratories funded under the European Union Sixth Framework Programme (FP6) Non-Targeted Effects (NOTE) integrated project. Materials and methods: Three batches of foetal bovine serum were tested; serum with high and low serotonin content from the intercomparison exercise as well as serum from the home laboratory. Three sets of human keratinocytes (HaCaT cell line) were cultured in DMEM:F12 medium supplemented with serum with high or low serotonin content or serum from the home laboratory and both donor and recipient HaCaT cells were plated. The donor HaCaT cells were irradiated (0.5 Gy) using a cobalt 60 teletherapy unit, the medium was harvested 1 hour post irradiation and transferred to the recipient HaCaT cells. Bystander induced cell death was measured by the clonogenic survival assay and the Alamar blue viability assay. Results: A significant reduction in cell survival, as measured by the clonogenic assay, and in cell viability, as measured by the Alamar blue assay, was observed in the recipient HaCaT cells treated with medium from irradiated cells compared to the cells treated with medium from unirradiated cells. No significant difference was found between the three batches of serum. Conclusions: The data suggest that in our cell system and with our endpoints (clonogenic assay and Alamar blue assay), serum serotonin levels do not play a role in bystander-induced cell death.
Bancroftian filariasis in Pondicherry, South India: 1. Pre-control epidemiological observations

SUMMARY A 5-year Integrated Vector Management (IVM) project was implemented in Pondicherry, South India, for the control of Bancroftian filariasis. The efficacy of the IVM strategy was compared with routine control strategy under the national programme. The present paper describes the pre-control epidemiological features of filariasis as determined by a mass blood survey in 1981. Of 24946 persons examined 8·41%; were microfilaraemic. Microfilaraemia prevalence was homogeneous throughout the study area. The prevalence and intensity of microfilaraemia were age dependent, and increased monotonically until about 20 years, following which there was a decline until about 40 years to become relatively stable in older age classes. The gender profiles of both prevalence and intensity of microfilaraemia showed no difference between the sexes until about 15 years of age, following which both were higher in males compared to females. The distribution of microfilarial counts was overdispersed, indicating aggregation of adult worms.
&bgr;1-Adrenergic Receptor Autoantibodies Mediate Dilated Cardiomyopathy by Agonistically Inducing Cardiomyocyte Apoptosis

Background— Antibodies to the &bgr;1-adrenergic receptor (&bgr;1AR) are detected in a substantial number of patients with idiopathic dilated cardiomyopathy (DCM). The mechanism whereby these autoantibodies exert their pathogenic effect is unknown. Here, we define a causal mechanism whereby &bgr;1AR-specific autoantibodies mediate noninflammatory cardiomyocyte cell death during murine DCM. Methods and Results— We used the &bgr;1AR protein as an immunogen in SWXJ mice and generated a polyclonal battery of autoantibodies that showed selective binding to the &bgr;1AR. After transfer into naive male hosts, &bgr;1AR antibodies elicited fulminant DCM at high frequency. DCM was attenuated after immunoadsorption of &bgr;1AR IgG before transfer and by selective pharmacological antagonism of host &bgr;1AR but not &bgr;2AR. We found that &bgr;1AR autoantibodies shifted the &bgr;1AR into the agonist-coupled high-affinity state and activated the canonical cAMP-dependent protein kinase A signaling pathway in cardiomyocytes. These events led to functional alterations in intracellular calcium handling and contractile function. Sustained agonism by &bgr;1AR autoantibodies elicited caspase-3 activation, cardiomyocyte apoptosis, and DCM in vivo, and these processes were prevented by in vivo treatment with the pan-caspase inhibitor Z-VAD-FMK. Conclusions— Our data show how &bgr;1AR-specific autoantibodies elicit DCM by agonistically inducing cardiomyocyte apoptosis.
Functional Role of GABAergic Innervation of the Cochlea: Phenotypic Analysis of Mice Lacking GABAA Receptor Subunits α1, α2, α5, α6, β2, β3, or δ

The olivocochlear efferent system is both cholinergic and GABAergic and innervates sensory cells and sensory neurons of the inner ear. Cholinergic effects on cochlear sensory cells are well characterized, both in vivo and in vitro; however, the robust GABAergic innervation is poorly understood. To explore the functional roles of GABA in the inner ear, we characterized the cochlear phenotype of seven mouse lines with targeted deletion of a GABAA receptor subunit (α1, α2, α5, α6, β2, β3, or δ). Four of the lines (α1, α2, α6, and δ) were normal: there was no cochlear histopathology, and cochlear responses suggested normal function of hair cells, afferent fibers, and efferent feedback. The other three lines (α5, β2, and β3) showed threshold elevations indicative of outer hair cell dysfunction. α5 and β2 lines also showed decreased effects of efferent bundle activation, associated with decreased density of efferent terminals on outer hair cells: although the onset of this degeneration was later in α5 (>6 weeks) than β2 (<6 weeks), both lines shows normal efferent development (up to 3 weeks). Two lines (β2 and β3) showed signs of neuropathy, either decreased density of afferent innervation (β3) or decreased neural responses without concomitant attenuation of hair cell responses (β2). One of the lines (β2) showed a clear sexual dimorphism in cochlear phenotype. Results suggest that the GABAergic component of the olivocochlear system contributes to the long-term maintenance of hair cells and neurons in the inner ear.
Electrode design to optimize ganglion cell activation in a retinal neuroprosthesis: A modeling study

Reduction of crosstalk in parallel stimulation of the retina is a major issue in improving the performance of retinal prostheses. A three-dimensional (3D) microelectrode array (MEA) has been proposed to mitigate the effect of the electric crosstalk. The efficacy of this configuration in focal electrical stimulation of retinal ganglion cells (RGCs) was investigated by way of an inhomogeneous but isotropic passive model of the retina. The effect of electrode diameter, height of chamber cavity and distance between electrode and RGCs on restricting the spread of electric fields within the retina was investigated. Finite element simulation demonstrated that in comparison with planar microelectrode arrays, an optimal 3D MEA configuration decreased the electric crosstalk and had the capacity to improve the spatial resolution of perceived images. Increasing chamber cavity height was found to become more effective in achieving simulated activation with closer proximity to the target RGCs.