Miracle-dz/UniFAR-FTUs huggingface dataset:
Transforming growth factor‐β1 enhances expression of brain‐derived neurotrophic factor and its receptor, TrkB, in neurons cultured from rat cerebral cortex

The effects of transforming growth factor (TGF)‐β1 on expression of brain‐derived neurotrophic factor (BDNF) and its high‐affinity receptor, TrkB, in neurons cultured from the cerebral cortex of 18‐day‐old embryonic rats were examined. BDNF mRNA was significantly increased from 24–48 hr after the TGF‐β1 treatment over 20 ng/ml. Accumulation of BDNF protein in the culture medium was also potentiated by TGF‐β1, although the intracellular content of BDNF was nearly unchanged. The enhancement of BDNF mRNA expression was suppressed by the co‐presence of decorin, a small TGF‐β‐binding proteoglycan that inhibits the biological activities of TGF‐βs. mRNA expression of full‐length TrkB, the bioactive high‐affinity receptor for BDNF, was also upregulated after treatment with TGF‐β1. These observations suggest that: 1) TGF‐β1 potentiates BDNF/TrkB autocrine or local paracrine system; and 2) the neurotrophic activity of TGF‐β1 is partly responsible for the BDNF induced by TGF‐β1 itself. To test this latter possibility, we examined the neuronal survival activity of TGF‐β1 with or without K252a, a selective inhibitor of Trk family tyrosine kinases. TGF‐β1 significantly enhanced neuronal survival, but the co‐presence of K252a completely suppressed the activity, demonstrating the involvement of Trk receptor signaling in TGF‐β1‐mediated neuronal survival in cultured rat cortical neurons. These results seem to be in line with recent findings by other investigators that some neurotrophic factors including BDNF require TGF‐βs as a cofactor to exert their neurotrophic activities. J. Neurosci. Res. 66:369–376, 2001. © 2001 Wiley‐Liss, Inc.
Hormonal regulation of spermatogenesis in the hypophysectomized rat: FSH maintenance of cellular viability during pubertal spermatogenesis.

The potential for follicle-stimulating hormone (FSH) to promote germ-cell survival and the cellular sites of FSH action were studied using a gonadally maturing (pubertal), hypophysectomized (Hx) rat model in which residual testosterone (T) activity was blocked by injections of an androgen-receptor antagonist, flutamide. Recombinant human FSH was given to androgen-deprived and androgen-blocked male rats at 27 days of age to determine maintenance of individual germ-cell types at 35 days of age. Follicle-stimulating hormone significantly increased testis weights and tubular diameters as compared with Hx and Hx-flutamide controls, although testis weights in FSH-treated animals were significantly lower than in pituitary-intact animals. Morphometric assays to determine ratios of germ cells to Sertoli cells and to determine the number of germ cells present per hour of development showed that the population of type A spermatogonia in the early stages of the cycle was not responsive to FSH. Follicle-stimulating hormone had a marked ability to maintain cell viability in the rapid, successive divisions that begin in the latter part of the cycle and that continue through the next cycle (i.e., from type A1 to A4 and from intermediate spermatogonia to type B spermatogonia to preleptotene spermatocytes to leptotene/zygotene spermatocytes to young pachytene spermatocytes). The data also suggest T responsiveness of these cell types since the Hx-FSH-flutamide group showed lower cell viability at the aforementioned steps when compared with the Hx-FSH group. Too few cell types were present at subsequent phases of spermatogenesis to allow a sensitive determination of FSH activity in the maintenance of cell viability. The data show the potential of FSH in the absence or relative absence of T activity to maintain cell viability. These data support the concept of overlapping and synergistic (or additive) effects of T and FSH in the immature rat and identify the cellular sites of FSH action.
Impaired Platelet Activation in Familial High Density Lipoprotein Deficiency (Tangier Disease)*

ATP binding cassette transporter A1 (ABCA1) is involved in regulation of intracellular lipid trafficking and export of cholesterol from cells to high density lipoproteins. ABCA1 defects cause Tangier disease, a disorder characterized by absence of high density lipoprotein and thrombocytopenia. In the present study we have demonstrated that ABCA1 is expressed in human platelets and that fibrinogen binding and CD62 surface expression in response to collagen and low concentrations of thrombin, but not to ADP, are defective in platelets from Tangier patients and ABCA1-deficient animals. The expression of platelet membrane receptors such as GPVI, α2β1 integrin, and GPIIb/IIIa, the collagen-induced changes in phosphatidylserine and cholesterol distribution, and the collagen-induced signal transduction examined by phosphorylation of LAT and p72syk and by intracellular Ca2+ mobilization were unaltered in Tangier platelets. The electron microscopy of Tangier platelets revealed reduced numbers of dense bodies and the presence of giant granules typically encountered in platelets from Chediak-Higashi syndrome. Further studies demonstrated impaired release of dense body content in platelets from Tangier patients and ABCA1-deficient animals. In addition, Tangier platelets were characterized by defective surface exposure of dense body and lysosomal markers (CD63, LAMP-1, LAMP-2, CD68) during collagen- and thrombin-induced stimulation and by abnormally high lysosomal pH. We conclude that intact ABCA1 function is necessary for proper maturation of dense bodies in platelets. The impaired release of the content of dense bodies may explain the defective activation of Tangier platelets by collagen and low concentrations of thrombin, but not by ADP.
Incidence and prevalence of Parkinson’s disease in Buenos Aires City, Argentina

Background and purpose: Epidemiologic studies of incidence and prevalence in Parkinson’s Disease (PD) show highly variable results. Despite the large number of studies performed worldwide during the last decades, little is known about its prevalence in South America and no incidence studies have been performed. The goal of this study is to assess the incidence and prevalence of PD in a health maintenance organization from Buenos Aires City, the capital city of Argentina.
Left ventricular diastolic function is related to glucose in a middle‐aged population

Abstract. Holzmann M, Olsson A, Johansson J, Jensen‐Urstad M (Karolinska Institute, Karolinska Hospital, Stockholm, Sweden). Left ventricular diastolic function is related to glucose in a middle‐aged population. J Intern Med 2002; 251: 415–420.
Cost evaluation of clinical laboratory in Taiwan’s National Health System by using activity-based costing

Abstract Background: To cope with the government’s policies to reduce medical costs, Taiwan’s healthcare service providers are striving to survive by pursuing profit maximization through cost control. This article aimed to present the results of cost evaluation using activity-based costing performed in the laboratory in order to throw light on the differences between costs and the payment system of National Health Insurance (NHI). Methods: This study analyzed the data of costs and income of the clinical laboratory. Direct costs belong to their respective sections of the department. The department’s shared costs, including public expenses and administrative assigned costs, were allocated to the department’s respective sections. A simple regression equation was created to predict profit and loss, and evaluate the department’s break-even point, fixed cost, and contribution margin ratio. Results: In clinical chemistry and seroimmunology sections, the cost per test was lower than the NHI payment and their major laboratory tests had revenues with the profitability ratio of 8.7%, while the other sections had a higher cost per test than the NHI payment and their major tests were in deficit. The study found a simple linear regression model as follows: “Balance=–84,995+0.543×income (R2=0.544)”. Conclusions: In order to avoid deficit, laboratories are suggested to increase test volumes, enhance laboratory test specialization, and become marginal scale. A hospital could integrate with regional medical institutions through alliances or OEM methods to increase volumes to reach marginal scale and reduce laboratory costs, enhancing the level and quality of laboratory medicine.
Use of Antibiotic-Loaded Polymethyl Methacrylate Beads in the Management of Musculoskeletal Sepsis — A Retrospective Study

Purpose. To assess the use of antibiotic-loaded polymethyl methacrylate beads in the management of chronic osteomyelitis of different aetiologies: infected osteosynthesis, infected open fractures, and haematogenous osteomyelitis. Methods. Records of 49 patients with chronic osteomyelitis who were treated at Department of Orthopaedics, Kasturba Medical College, from 1995 to 1999 were studied retrospectively. The diagnosis of chronic osteomyelitis was made on the basis of clinical and radiographic features. Of the 49 patients, 4 had haematogenous osteomyelitis, which later proved to be tuberculosis, and were thus excluded. Antibiotic-loaded acrylic beads were implanted in the remaining patients after thorough debridement. The implant was removed primarily in 16 patients with infected osteosynthesis, who then underwent decompression and sequestrectomy. All wounds were closed primarily. Peri-operative antibiotics were given for 7 days. Beads were removed at the end of 3 weeks followed by bone grafting in 26 patients. Patients were followed up for an average period of 3.7 years. Results. The infective organisms were sensitive to gentamycin in 26 cases and resistant in 19 cases; 14 cases were sensitive to cefuroxime, 11 to cloxacillin, 8 to ampicillin, and 5 to cotrimoxazole. Seven cases were resistant to all antibiotics tested. Of the 19 patients with gentamycin-resistant infection, only one had a poor result. No adverse systemic side-effects such as ototoxicity or nephrotoxicity were seen. Infection did not recur in 39 patients, but 6 patients had low-grade persistent infection at the last follow-up visit. Conclusion. In chronic infections, especially those following osteosynthesis, antibiotic beads are a valuable adjuvant. The most valuable advantage is that the wound can be closed primarily, thereby reducing the incidence of nosocomial infections and requirement of nursing care.
The Twisted Abdomen Phenotype of Drosophila POMT1 and POMT2 Mutants Coincides with Their Heterophilic Protein O-Mannosyltransferase Activity*

Walker-Warburg syndrome, caused by mutations in protein O-mannosyltransferase-1 (POMT1), is an autosomal recessive disorder characterized by severe brain malformation, muscular dystrophy, and structural eye abnormalities. As humans have a second POMT, POMT2, we cloned each Drosophila ortholog of the human POMT genes and carried out RNA interference (RNAi) knock-down to investigate the function of these proteins in vivo. Drosophila POMT2 (dPOMT2) RNAi mutant flies showed a “twisted abdomen phenotype,” in which the abdomen is twisted 30–60°, similar to the dPOMT1 mutant. Moreover, dPOMT2 interacted genetically with dPOMT1, suggesting that the dPOMTs function in collaboration with each other in vivo. We expressed dPOMTs in Sf21 cells and measured POMT activity. dPOMT2 transferred a mannose to the dystroglycan protein only when it was coexpressed with dPOMT1. Likewise, dPOMT1 showed POMT activity only when coexpressed with dPOMT2, and neither dPOMT showed any activity by itself. Each dPOMT RNAi fly totally reduced POMT activity, despite the specific reduction in the level of each dPOMT mRNA. The expression pattern of dPOMT2 mRNA was found to be similar to that of dPOMT1 mRNA using whole mount in situ hybridization. These results demonstrate that the two dPOMTs function as a protein O-mannosyltransferase in association with each other, in vitro and in vivo, to generate and maintain normal muscle development.
Stimulation of nonspecific resistance to infection induced by 6-O-acyl muramyl dipeptide analogs in mice

The experimental system utilized in investigating the correlation between the chemical structures of muramyl peptides and their protective activities in the sepsis type of systemic infections caused by Escherichia coli was applied in evaluating the enhancement of resistance to infection induced by 32 synthetic glycopeptide analogs, including 6-O-acyl derivatives and 1-alpha-O-benzyl derivatives of muramyl dipeptide (N-acetyl muramyl-L-alanyl-D-isoglutamine). In assessing the 6-O-acyl derivatives of muramyl dipeptide, we found that the degree of protective activity was attributable to the kinds of fatty acids introduced. Acylation of the 6-hydroxy group on the muramic acid moiety in muramyl dipeptide with natural mycolic acid or a synthetic fatty acid possessing either an alpha-branched or an alpha-branched, beta-hydroxylated group resulted in a decrease in or a disappearance of the protective activity of muramyl dipeptide. Acylation with a normal fatty acid or an iso fatty acid resulted in a retention or enhancement of muramyl dipeptide activity. The activity of acylated derivatives containing linear fatty acids was stimulated by increasing the chain length up to 18 carbon atoms. The highest degree of protective activity occurred with the derivatives acylated with straight-chain fatty acids, particularly with the derivatives acylated with palmitic acid and arachidic acid. Benzylation of the 1-hydroxy group of muramyl dipeptide resulted in a decrease in or a loss of protective activity.
Clonal Diversity of Escherichia coli Isolates Carrying Plasmid-Mediated Fosfomycin Resistance Gene fosA3 from Livestock and Other Animals

In Escherichia coli, fosfomycin resistance is uncommon and is mainly caused by mutations in the chromosomally encoded drug transporters ([1][1]). Nonetheless, recent studies have demonstrated the emergence of fosA3 , the plasmid-mediated fosfomycin resistance gene, among CTX-M-producing and
Radiographic findings of the medial humeral epicondyle in 200 canine elbow joints

Summary Objectives: To determine the frequency and radiographic aspect of medial humeral epicondylar lesions as a primary or concomitant finding and to evaluate the association with osteoarthritis. Methods: Medical records of dogs diagnosed with elbow lameness were reviewed. Inclusion criteria for this study were a complete clinical examination, a complete set of digital radiographs and a final diagnosis made by computed tomography or magnetic resonance imaging and arthroscopy. Changes of the medial humeral epicondyle were recorded and correlated with the radiographic osteoarthritis and final diagnosis. Results: Eighty of the 200 elbows showed changes of the medial humeral epicondyle. In 12 of these 80 elbows, changes of the medial epicondyle were the only findings within the joint, and these elbows were diagnosed with primary flexor enthesopathy. In the remaining 68 elbows, other concomitant elbow pathologies were found. In those cases of concomitant epicondylar changes, high grades of osteoarthritis were recorded, while most elbows with primary flexor enthesopathy showed a low grade of osteoarthritis. Clinical significance: Changes of the medial humeral epicondyle are often considered clinically unimportant and are regarded as an expression of osteoarthritis. This study showed the relatively frequent presence of epicondylar changes of which the majority were considered concomitant to a primary elbow problem. If changes of the medial humeral epicondyle are the only pathologic finding (primary flexor enthesopathy) they should be considered as the cause of lameness and not as a sign of osteoarthritis.
Severe Developmental Prosopagnosia in a Child With Superior Intellect

Developmental prosopagnosia, a lifelong inability to learn and recognize familiar faces, has rarely been reported, and there are even fewer cases that have been studied during childhood. Of the cases studied during childhood, significant apperceptive features to the face recognition defect have been noted. We had an opportunity to conduct extensive standard and experimental neuropsychological, psychophysiological, and neuroanatomical studies in a five-year-old child with severe developmental prosopagnosia. The subject was intellectually gifted (FSIQ130), but had a marked discrepancy between verbal and nonverbal abilities (VIQ140, PIQ110). Although some visual perceptual weaknesses were apparent, the subjects face recognition defect was found to cnform most closely to the associative type, and he did not have visual recognition deficits for any categories of nonunique entities. A novel finding was that the childs covert recognition of familiar faces based on an autonomic index was normal, suggesting that as in some adult-onset cases, the brain is capable of acquiring some information about familiar faces, even without conscious recognition. The child also had normal judgments of facial emotional expressions. Our report extends the understanding of the neuropsychological features of developmental prosopagnosia, and may help narrow the search for neuroanatomical correlates of this condition, which have yet to be identified.
[Predictive factors of successful selective laser trabeculoplasty in open-angle glaucoma].

BACKGROUND The aim of this study was to determine factors that predict successful selective laser trabeculoplasty (SLT) in open-angle glaucoma (OAG). PATIENTS AND METHODS In 122 eyes suffering from OAG, treatment was carried out with a frequency-doubled, Q-switched Nd:YAG laser (532 nm). The intraocular pressure (IOP) was measured before the treatment and 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78 and 84 months thereafter. Success was defined as an IOP reduction exceeding 20 % of the pretreatment IOP. Correlations between successful SLT and baseline IOP, age, sex, hypertension, diabetes mellitus, family history of glaucoma, previous anterior segment surgery, the grade of trabecular meshwork pigmentation, laser energy used, and local antiglaucoma therapy were determined. RESULTS The mean follow-up time was 43.4 months (SD: 25.6). The mean pretreatment IOP was 22.5 mmHg (SD: 2.8). The success rate after 12 months determined from the Kaplan-Meier survival analysis was 88 %, after 24 months 79 %, after 36 months 67 %, after 48 months 58 %, after 60 months 49 % and after 84 months 48 %. We found statistically significant negative correlation betweens successful SLT and the grade of trabecular meshwork pigmentation (r = -0.234; p = 0.01), diabetes mellitus (r = -0.223; p = 0.014). We found no statistically significant correlations between successful SLT and baseline IOP, age, sex, hypertension, family history of glaucoma, previous anterior segment surgery, laser energy used, local antiglaucoma therapy. CONCLUSION SLT success in OAG with a mean follow-up time of 43.4 months was significantly predicted by the lower grade of trabecular meshwork pigmentation and the absence of diabetes mellitus.
Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy. SAMPLE Study Group. Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation.

BACKGROUND In cross-sectional studies, ambulatory blood pressure (ABP) correlates more closely than clinic BP with the organ damage of hypertension. Whether ABP predicts development or regression of organ damage over time better than clinic BP, however, is unknown. METHODS AND RESULTS In 206 essential hypertensive subjects with left ventricular hypertrophy (LVH), we measured clinic supine BP, 24-hour ABP, and left ventricular mass index (LVMI, echocardiography) before and after 12 months of treatment with lisinopril (20 mg UID) without or with hydrochlorothiazide (12.5 or 25 mg UID). Measurements included random-zero, clinic orthostatic, and home BP. In all, 184 subjects completed the 12-month treatment period. Before treatment, clinic supine BP was 165 +/- 15/105 +/- 5 mm Hg (systolic/diastolic), 24-hour average BP was 149 +/- 16/95 +/- 11 mm Hg, and LVMI was 158 +/- 32 g/m2. At the end of treatment, they were 139 +/- 12/87 +/- 7 mm Hg, 131 +/- 12/83 +/- 10 mm Hg, and 133 +/- 26 g/m2, respectively (P < .01 for all). Before treatment, LVMI did not correlate with clinic BP, but it showed a correlation with systolic and diastolic 24-hour average BP (r = .34/.27, P < .01). The LVMI reduction was not related to the reduction in clinic BP, but it was related to the reduction in 24-hour average BP (r = .42/.38, P < .01). Treatment-induced changes in average daytime and nighttime BPs correlated with LVMI changes as strongly as 24-hour BP changes. No substantial advantage over clinic supine BP was shown by clinic orthostatic, random-zero, and home BP. CONCLUSIONS In hypertensive subjects with LVH, regression of LVH was predicted much more closely by treatment-induced changes in ABP than in the clinic BP. This provides the first longitudinally controlled evidence that ABP may be clinically superior to traditional BP measurements.
Identification of a novel p53 promoter element involved in genotoxic stress-inducible p53 gene expression

p53 is recruited in response to DNA-damaging genotoxic stress and plays an important role in maintaining the integrity of the genome. We show that exposure of cells to various genotoxic agents, including anticancer drugs such as mitomycin and 5-fluorouracil, results in an increase in p53 mRNA levels and in p53 promoter activation, indicating that the p53 genotoxic stress response is partly regulated at the transcriptional level. The results of the p53 promoter analysis show that a novel p53 promoter element, termed a p53 core promoter element (from -70 to -46), is essential for basal p53 promoter activity and promoter activation induced by genotoxic agents such as anticancer drugs and UV. Although a kappa B motif partially overlaps with this element and those genotoxic agents activate NF-kappa B, it does not play a major role in p53 genotoxic stress response: NF-kappa B p65 expression did not induce significant p53 promoter activation, and NF-kappa B inhibitors (N-acetyl cysteine and I kappa B alpha) did not inhibit genotoxic stress-inducible p53 promoter activation. Finally, we characterized nuclear factors, the binding of which to the p53 core promoter element is essential for basal p53 promoter activity and p53 promoter activation induced by genotoxic agents.
Variant alleles of TGFB1 and TGFBR2 are associated with a decreased risk of gastric cancer in a Chinese population

Growing evidence suggests that the transforming growth factor β (TGF‐β) signaling pathway occupies a central position in the signaling networks that control cell growth and differentiation. TGF‐β1 and its receptor TGF‐βRII have been correlated with the development of certain forms of cancer, including gastric cancer. We hypothesized that functional genetic variants in TGFB1 and TGFBR2 are associated with gastric cancer risk. To test this hypothesis, we genotyped C‐509T and Leu10Pro polymorphisms in TGFB1 and G‐875A variant in TGFBR2, using the primer‐introduced restriction analysis (PIRA)‐PCR assay, in a case–control study of 675 gastric cancer cases and 704 healthy controls in a Chinese population. We found that the variant alleles of the promoter polymorphisms, TGFB1 C‐509T and TGFBR2 G‐875A, were associated with a significantly decreased risk of gastriccancer [adjusted odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.52–0.82 for −509CT/TT and adjusted OR = 0.67, 95% CI = 0.53–0.85 for −875GA/AA]. Furthermore, subjects with both variant genotypes of the TGFB1 C‐509T and TGFBR2 G‐875A were associated with a significantly (56%) decreased risk of gastric cancer (adjusted OR = 0.44, 95% CI = 0.32–0.62). These findings indicate, for the first‐time, that the functional variants in the promoter of TGFB1 and TGFBR2 might contribute to gastric cancer susceptibility. © 2006 Wiley‐Liss, Inc.