Miracle-dz/UniFAR-FTUs huggingface dataset:
Mercury‐induced autoimmunity in the absence of IL‐4

In susceptible H‐2s mice, mercuric chloride (HgCl2) induces an autoimmune syndrome characterized by production of anti‐nucleolar antibodies (ANoA) and increased serum levels of IgG1 and IgE antibodies. The increase in serum IgG1 and IgE, which are under IL‐4 control, suggests a role for the Th2 subset in the induction of this syndrome. We have previously shown that administration of IL‐12, a potent Th1‐promoting cytokine, resulted in a dramatic reduction of the HgCl2‐induced anti‐nucleolar antibody titres and inhibited serum IgG1 increase. These results suggest that Th1 T cells can down‐regulate ANoA, and support a role for the Th2 subset in ANoA production, possibly via IL‐4. To examine the role of IL‐4 in this syndrome, C57Bl/6 mice (H‐2b) with a targeted deletion of the IL‐4 gene were mated with A.SW mice (H‐2s) to yield H‐2s mice lacking IL‐4. We then analysed ANoA and serum immunoglobulin levels in these mice after HgCl2 treatment. While mercury‐treated IL‐4−/− H‐2s mice had virtually no detectable serum IgG1 or IgE, and very low levels of IgG1 ANoA, these mice had levels of IgG2a and IgG2b class ANoA comparable to mercury‐treated IL‐4+ H‐2s mice, indicating that IL‐4 is not required for the ANoA response in mercury‐induced autoimmunity.
Parathyroid proliferations

With wide use of fine‐needle aspirates (FNA) for investigation of thyroid nodules, a growing number of parathyroid glands are being inadvertently aspirated for cytologic study. Aiming to determine the effectiveness of FNA to differentiate between parathyroid and thyroid lesions, all cases aspirated initially as thyroid nodules and that had a final histologic diagnosis of parathyroid lesion were retrieved from the authors' files and were systematically reviewed to delineate possible specific diagnostic criteria.
HER2 testing of multifocal invasive breast carcinoma: how many blocks are enough?

OBJECTIVES To determine the diagnostic yield of testing multiple blocks for HER2 in cases of multifocal breast carcinoma. METHODS We identified 246 consecutive cases of multifocal invasive breast carcinoma in which HER2 was tested on more than 1 tumor focus. We performed an audit of all cases with respect to tumor size, grade, and histologic type. RESULTS HER2 status was concordant between multiple foci in 230 (93.5%) of 246 cases, with the largest focus having the most positive HER2 result in 242 (98.4%) of 246 cases. We did not find a single case in which a smaller focus demonstrated a more positive HER2 status unless this focus was either higher grade or different histologically. CONCLUSIONS Our findings support the evaluation of HER2 on the largest focus, with additional testing on smaller foci having a different histologic type or higher grade.
The Course of Depressive Illness in General Practice

Objective: Depression is reported to be common in primary care settings and to have a high likelihood of relapse during the 4- to 6-month period following initial symptomatic improvement. However, most prospective studies of long-term treatment of depression have been conducted with patients selected for participation in placebo-controlled drug protocols or psychiatric clinics associated with tertiary referral centres. Method: We examined the treatment course and outcome of outpatients with major depressive episode treated in a primary care setting. The general practitioners were free to choose the treatment and its duration. Their only obligation was to assess the therapeutic outcome in terms of efficacy and safety and to perform a final evaluation at the end of the 6-month observation period or, if the patient was treated for a shorter period, at the end of the treatment. Results: Of the 476 patients involved, 308 (64.7%) responded to treatment and remained well, 117 (24.6%) showed no response, and 51 (10.7%) had an early relapse after initial improvement. Among the studied demographic, clinical, and therapeutic factors, the history of recurrent depression was the only variable with a significant effect size in predicting the course of the illness. Conclusion: Patients with recurrent depression were at higher risk of relapse or nonresponse.
Evaluación de aislamientos de Trichoderma spp. contra Rhizoctonia solani y Sclerotium rolfsii bajo condiciones in vitro y de invernadero

Se evaluo la eficacia biologica de ocho aislamientos de Trichoderma spp. provenientes de suelos de Colombia para el control de los agentes causales de volcamiento, Sclerotium rolfsii y Rhizoctonia solani , bajo condiciones in vitro y de invernadero. Los analisis in vitro mostraron la capacidad antagonica de todos los aislamientos evaluados. En condiciones de invernadero, cuatro aislamientos fueron altamente eficaces contra S. rolfsii en plantas de frijol en semillero (>90% de reduccion de la enfermedad) y dos aislamientos fueron eficaces contra R. solani en plantas de algodon en semillero (58 y 61% de reduccion de la enfermedad). El analisis UP-PCR y DS-PCR permitio determinar tres grupos de aislamientos; dentro de estas asociaciones formadas no se encontro ninguna relacion evidente entre la posicion en el dendrograma y la actividad antagonica, pero si permitio separar las especies de Trichoderma por grupos, e incluso encontrar diferencias dentro de aislamientos de una misma especie. Los resultados muestran que el comportamiento micoparasitico de los aislamientos de Trichoderma spp. varia segun el hongo fitopatogeno, evidenciando una amplia especificidad del antagonista por su sustrato, es decir por el hongo atacado; por lo tanto es necesario realizar cuidadosas selecciones del aislamiento de Trichoderma que se utilice en programas de control de fitopatogenos.
Olig2 overexpression accelerates the differentiation of mouse embryonic stem cells into oligodendrocyte progenitor cells in vitro

Oligodendrocyte progenitor cells (OPCs) transplantation is receiving considerable attention in the field of regenerative medicine therapy for demyelinating diseases. Although embryonic stem cells (ESCs) have been successfully induced to differentiate into OPCs with cytokines cocktails in vitro, the regulatory roles of many key transcription factors in this process are not clear. Here, we introduced oligodendrocyte lineage transcription factor 2 (Olig2), a basic helix‐loop‐helix transcription factor, into mouse embryonic stem cells (mESCs) to investigate its effects on the differentiation of mESCs into OPCs. The results showed that Olig2 overexpression alone did not affect pluripotency of mESCs, but in the stimulation of differentiating cocktails, Olig2 accelerated mESCs to differentiate into OPCs, shortening the induction time span from normal 21 days to 11 days. Further study demonstrated the Olig2‐mESCs derived OPCs were able to differentiate into C‐type natriuretic peptid (CNP) and Myelin Basic Protein (MBP) positive mature oligodendrocytes (OLs) in vitro, suggesting these induced OPCs might be favorable for myelin regeneration in vivo.
Effects of Specific Antibodies against Streptococcus pneumoniae on Pharmacodynamic Parameters of β-Lactams in a Mouse Sepsis Model

ABSTRACT A dose-ranging study to investigate the in vivo effects of the presence of specific antibodies on the efficacy of β-lactam treatment of sepsis caused by Streptococcus pneumoniae (non-β-lactam-susceptible serotype 6B isolate) was performed with a BALB/c mouse model. Hyperimmune serum was obtained from mice immunized with the heat-inactivated strain. The rate of mortality was 100% in nontreated animals in the absence of specific antibodies. A single injection of a one-half or one-quarter dilution of hyperimmune serum produced 60 to 40% survival rates. In the absence of specific antibodies, the minimal effective doses of amoxicillin and cefotaxime that produced survival rates of 100 and 80% were 25 and 50 mg/kg of body weight (three times a day for up to six doses), respectively. These doses produced times that the levels in serum remained above the MIC (ΔT > MICs) ≈30% of the dosing interval. When specific antibodies were present (by administration of a one-half or one-quarter dilution of hyperimmune serum), the minimal effective doses of the antibiotics were 3.12 and 6.25 mg/kg (≈8 times lower), with the ΔT > MICs being approximately 3 and 5% of the dosing interval for amoxicillin and cefotaxime, respectively. This in vivo combined pharmacodynamic effect offers possibilities that can be used to address penicillin resistance.
Changes in 17 beta,20 alpha-hydroxysteroid dehydrogenase activity supporting an increase in the estrogen/progesterone ratio of human fetal membranes at parturition.

OBJECTIVE Our purpose was to measure the activity of the reversible enzyme 17 beta,20 alpha-hydroxysteroid dehydrogenase around parturition with estrogen and progestogen substrates. STUDY DESIGN Classic kinetic studies and explant cultures were used to determine kinetic parameters and net enzyme activities in both oxidative and reductive directions for both sets of substrates. RESULTS Affinity constant values for estrone, estradiol, and 20 alpha-dihydroprogesterone were 1 to 8 mumol/L. Affinity constant for progesterone was 9 to 25 mumol/L. Maximal velocities for all substrates in the chorion were 20- to 70-fold higher than in amnion and severalfold higher for estrogen substrates compared with the progestins. Around parturition there was a significant change toward net formation of the stronger estrogen (estradiol) and the weaker progestin (20 alpha-dihydroprogesterone), suggesting an increase in the local estrogen/progesterone ratio. CONCLUSION The enzyme 17 beta,20 alpha-hydroxysteroid dehydrogenase may be an important regulator of the local estrogen/progesterone ratio in fetal membranes around the time of parturition.
[Treatment of reno-ureteral lithiasis with ESWL in obese patients. Apropos of 150 patients].

OBJECTIVES Obesity is considered a significant risk factor for diseases such as hypertension, diabetes, coronary artery disease, and metabolic diseases, increasing considerably the risk for surgery. We have treated with ESWL a significant number of patients with the aim of avoiding operations which could be long and have associated complications due to the patient's condition. METHODS From April 2000 to May 2002 we treated 150 obese patients with kidney and/or ureteral stones using a Nova Ultima lithotripter. 94% of the patients were treated with a neuroleptoanalgesic drug, and 6% of the cases required narcotic-neuroleptoanalgesia. 85% of the cases were admitted for 24 hours, and 15% were outpatient. 94 males and 56 females who weighted more than 90 kg (91-141 kg) and more than 80 kg (80-127 kg) respectively were treated. Mean age was 41 years (range 20-72). 134 stones were located in the kidney, 27 in the pelvis and 16 in the ureter (25 patients presented bilateral lithiasis and 2 one ureteral stone and one homolateral kidney stone). Mean stone size was 12 mm. Stone track down was easy in 64% of the cases and difficult in 36%, mainly ureteral and pelvic stones. All patients received 3,000 shock waves at 21-22 KV and high energy with an average time per session of 35 minutes. Ultrasound tracking was preferred in 80% of the patients. RESULTS Results at three months were: 72% stone-free, 9% < 4 mm, 14% > = 4 mm, and 5% failures. Best results were obtained in pelvic and lumbar ureter stones (88%). Mean retreatment was 1.6, with one additional session in 34 patients, two sessions in 8, and three sessions in 5. CONCLUSIONS In the treatment of urolithiasis in obese patients, lithotriptor machine characteristics and operator experience are very important. The knowledge and the application of stone tracking systems allow the urologist to obtain a higher percentage of stone free patients. These techniques are important in these patients because positioning is key to obtain a good result. The indication of ESWL in obese patients is a good choice but selection criteria should be respected. The percentage of stone free patients at three months has been satisfactory and complications are similar to those published by other authors.
Substrate Specificity of Human Kallikrein 6

Human kallikrein 6 (hK6) is abundantly expressed in the central nervous system and is implicated in demyelinating disease. This study provided biochemical data about the substrate specificity and activation of hK6 by glycosaminoglycans and by kosmotropic salts, which followed the Hofmeister series. The screening of fluorescence resonance energy transfer (FRET) peptide families derived from Abz-KLRSSKQ-EDDnp resulted in the finding that Abz-AFRFSQ-EDDnp (where Abz is ortho-aminobenzoic acid and EDDnp is N-[2,4-dinitrophenyl]ethylenediamine)) is the best synthetic substrate described so far for hK6 (kcat/Km = 38,667 s–1 mm–1). It is noteworthy that the AFRFS sequence was found as a motif in the amino-terminal domain of seven human ionotropic glutamate receptor subunits. We also examined the hK6 hydrolytic activity on FRET peptides derived from human myelin basic protein, precursor of the Aβ amyloid peptide, reactive center loop of α1-antichymotrypsin, plasminogen, and maturation and inactivation cleavage sites of hK6, which were described earlier as natural substrates for hK6. The best substrates were derived from myelin basic protein. The hK6 maturation cleavage site was poorly hydrolyzed, and no evidence was found to support a two-step self-activation process reported previously. Finally, we assayed FRET peptides derived from sequences that span the cleavage sites for activation of protease-activated receptors (PAR) 1–4, and only the substrate with the PAR 2 sequence was hydrolyzed. These results further supported the hypothesis that hK6 expressed in the central nervous system is involved in normal myelin turnover/demyelination processes, but it is unlikely to self-activate. This report also suggested the possible modulation of ionotropic glutamate receptors and activation of PAR 2 by hK6.
Bad luck and cancer: Does evolution spin the wheel of fortune?

tion [3]. Additionally, epidemiological data can be biased as a result of some cancer types attracting more attention from researchers than others. Nevertheless, we think that their publication is game-changing and paves the way to new directions in our understanding of cancer etiology by calling for a shift in cancer research from the current, very detailed description of cellular mechanisms, to a wider multi-scale integrative approach. While their study is the first to focus on the association between the number of stem cells and cancer incidence at a tissue level, previous works have studied similar patterns at different organismal levels. For example the Boyd Orr cohort, a long-term population study, has shown that the number of cells (measured by leg length at birth) is
College of American Pathologists/American College of Medical Genetics proficiency testing for constitutional cytogenomic microarray analysis

Purpose: To evaluate the feasibility of administering a newly established proficiency test offered through the College of American Pathologists and the American College of Medical Genetics for genomic copy number assessment by microarray analysis, and to determine the reproducibility and concordance among laboratory results from this test.Methods: Surveys were designed through the Cytogenetic Resource Committee of the two colleges to assess the ability of testing laboratories to process DNA samples provided and interpret results. Supplemental questions were asked with each Survey to determine laboratory practice trends.Results: Twelve DNA specimens, representing 2 pilot and 10 Survey challenges, were distributed to as many as 74 different laboratories, yielding 493 individual responses. The mean consensus for matching result interpretations was 95.7%. Responses to supplemental questions indicate that the number of laboratories offering this testing is increasing, methods for analysis and evaluation are becoming standardized, and array platforms used are increasing in probe density.Conclusion: The College of American Pathologists/American College of Medical Genetics proficiency testing program for copy number assessment by cytogenomic microarray is a successful and efficient mechanism for assessing interlaboratory reproducibility. This will provide laboratories the opportunity to evaluate their performance and assure overall accuracy of patient results. The high level of concordance in laboratory responses across all testing platforms by multiple facilities highlights the robustness of this technology.
Pathology of idiopathic dystonia: findings from genetic animal models.

Dystonia is a common movement disorder which is thought to represent a disease of the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e. the neuroanatomic and neurochemical basis, is still a mystery. Research in dystonia is complicated by the existence of various phenotypic and genotypic subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions. In neurological diseases in which no obvious neuronal degeneration can be found, such as in idiopathic dystonia, the identification of a primary defect is difficult, because of the large number of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain. The variable response to pharmacological agents in patients with idiopathic dystonia supports the notion that the underlying biochemical dysfunctions vary in the subtypes of idiopathic dystonia. Hence, in basic research it is important to clearly define the involved type of dystonia. Animal models of dystonias were described as limited. However, over the last years, there has been considerable progress in the evaluation of animal models for different types of dystonia. Apart from animal models of symptomatic dystonia, genetic animal models with inherited dystonia which occurs in the absence of pathomorphological alterations in brain and spinal cord are describe. This review will focus mainly on genetic animal models of different idiopathic dystonias and pathophysiological findings. In particular, in the case of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case of the genetically dystonic hamster (dt(sz)), a model of paroxysmal dystonic choreoathetosis has been used, as these show great promise in contributing to the identification of underlying mechanisms in idiopathic dystonias, although even a proper animal model will probably never be equivalent to a human disease. Several pathophysiological findings from animal models are in line with clinical observations in dystonic patients, indicating abnormalities not only in the basal ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through clinical studies and neurochemical data several similarities were found in the genetic animal models, although the current data indicates different defects in dystonic animals which is consistent with the notion that dystonia is a heterogenous disorder. Different supraspinal dysfunctions appear to lead to manifestation of dystonic movements and postures. In addition to increasing our understanding of the pathophysiology of idiopathic dystonia, animal models may help to improve therapeutic strategies for this movement disorder.
The Effect of Taxpayer Education on Voluntary Tax Compliance, among Smes in Mwanza City- Tanzania

The study sought to establish the effect of taxpayer education on voluntary tax compliance, among Small and Micro-Enterprises (SMEs) in Mwanza City- Tanzania. Specifically, the study establishes the level of taxpayer education among SMEs, the level of voluntary tax compliance among the SMEs and the effect of taxpayer education on the level of voluntary tax compliance, among entrepreneurs in Mwanza City. A cross-sectional descriptive research design was used. Both primary and secondary data were collected using a questionnaire. 85% of the respondents, admitted to have gained understanding on the basic tax laws and procedures, while 15% showed that there was no improvement in understanding the basic tax laws. 78.7% of the respondents agreed that through the taxpayer education, they had been able to understand and become aware of their taxpayer rights and obligations. 21.3% of the respondents stated that taxpayer education, had not been able to help them in understanding and becoming aware of their tax rights and obligations. 83% of the respondents agreed that taxpayer education helped them in understanding clearly the procedure of paying taxes, while 17% claimed that despite the tax education they received, they did not understand clearly the procedure of paying taxes. Responses from the staff indicated that 80% of the returns were lodged timely, while the remaining 20% were not lodged within statutory periods and would attract penalties and fines for late filling. Of the returns lodged 67% declared accurate tax liability, while the remainder contained errors. Additional taxes were assessed through auditing. 78% of those who were required to pay taxes, actually paid within the stipulated time frame according to the law, while the remaining 22% were late in paying taxes, which necessitated the use of enforcement strategies. It is thus recommended that taxation should be taught at all levels of education, starting from primary schools upwards with an emphasis on promoting voluntary tax compliance.
On the semiadditivity of analytic capacity and planar Cantor sets

It has been recently proved that analytic capacity, γ, is semiadditive. This result is a consequence of the comparability between γ and γ+, a version of γ originated by bounded Cauchy potentials of positive measures. In this paper we describe the main ideas involved in the proof of this result and we give a complete proof of it in the particular case of the N -th approximation of the corner quarters Cantor set.
Human Prostatic Acid Phosphatase, an Authentic Tyrosine Phosphatase, Dephosphorylates ErbB-2 and Regulates Prostate Cancer Cell Growth*

Cellular prostatic acid phosphatase (cPAcP), an authentic tyrosine phosphatase, is proposed to function as a negative growth regulator of prostate cancer (PCa) cells in part through its dephosphorylation of ErbB-2. Nevertheless, the direct interaction between cPAcP and ErbB-2 has not been shown nor the specific dephosphorylation site of ErbB-2 by cPAcP. In this report, our data show that the phosphorylation level of ErbB-2 primarily at Tyr1221/2 correlates with the growth rate of both LNCaP and MDA PCa2b human PCa cells. Further, cPAcP reciprocally co-immunoprecipitated with ErbB-2 in a non-permissive growth condition. Expression of wild type cPAcP, but not inactive mutant, by cDNA in cPAcP-null LNCaP C-81 cells results in decreased tyrosine phosphorylation of ErbB-2 including Tyr1221/2. Concurrently, Tyr317 phosphorylation of p52Shc, proliferating cell nuclear antigen expression, and cell growth are decreased in these cells. Conversely, decreased cPAcP expression by short hairpin RNA in LNCaP C-33 cells was associated with elevated phosphorylation of ErbB-2 initially at Tyr1221/2. Its downstream p52Shc, ERK1/2, Akt, Src, STAT-3, and STAT-5 were activated, and cell proliferation, proliferating cell nuclear antigen, and cyclin D1 expression were increased. Stable subclones of C-33 cells by small interfering PAcP had elevated Tyr1221/2 phosphorylation of ErbB-2 and exhibited androgen-independent growth and increased tumorigenicity in xenograft female animals. In summary, our data together indicate that in prostate epithelia, cPAcP interacts with and dephosphorylates ErbB-2 primarily at Tyr1221/2 and hence blocks downstream signaling, leading to reduced cell growth. In PCa cells, decreased cPAcP expression is associated with androgen-independent cell proliferation and tumorigenicity as seen in advanced hormone-refractory prostate carcinomas.