Miracle-dz/UniFAR-FTUs huggingface dataset:
Temporal Changes in Cellular Repopulation and Collagen Fibril Remodeling and Regeneration After Allograft Anterior Cruciate Ligament Reconstruction

Background: Distinguishing recipient cells from donor ligament cells is difficult in the early graft-healing phase after anterior cruciate ligament (ACL) reconstruction. The ability to track the distribution and differentiation of recipient cells using genetically engineered transgenic (Tg) animals would have significant clinical and research effects on graft healing after ACL reconstruction. Hypothesis: Kusabira-Orange Tg pigs may allow the tracking of recipient cells infiltrating the graft after ACL reconstruction. The repopulation of recipient cells within the graft would be apparent even in the early graft-healing phase when necrotic donor cells are still present. Study Design: Descriptive laboratory study. Methods: In 17 genetically engineered Tg pigs, which carried the red fluorescent protein Kusabira-Orange, ACL reconstruction was performed on the right knee using a digital flexor tendon harvested from wild-type pigs. Tissue samples harvested at different time points were subjected to histological, immunohistochemical, and electron microscopic analyses. Results: At 3 weeks postoperatively, recipient cells expressing red fluorescence embraced the graft and were infiltrating the central part of the graft. These cells with oval nuclei gradually infiltrated the gap of collagen fibers, losing their regular orientation. At 6 weeks, cellularity within the graft had doubled to match that of the native ACL, while acellular necrotic regions still existed centrally. Ubiquitous cellular distributions resembling the native ACL were observed at 24 weeks. Electron microscopic analysis showed that the mean collagen fibril diameter and density gradually decreased over 24 weeks. Conclusion: Genetically engineered pigs carrying the Kusabira-Orange gene were useful animal models for analyzing intrinsic and extrinsic cellular dynamics during the course of graft healing after ACL reconstruction. Cellular repopulation by recipient cells occurred in the very early stage, and the cellular distribution within the graft resembled that in the native ACL by 24 weeks, but the reconstructed graft had not restored the ultrastructure of the native ACL by that stage. Clinical Relevance: In allograft ACL reconstruction in a pig model, cellular repopulation was completed by 24 weeks after surgery, but the collagen matrix had not resumed the ultrastructure of the native ACL. Surgeons should be aware that risks may remain with returning to sports activities at 24 weeks after surgery.
Thymic B lymphocyte clones from patients with myasthenia gravis secrete monoclonal striational autoantibodies reacting with myosin, alpha actinin, or actin

Striational autoantibodies (StrAb), which react with elements of skeletal muscle cross-striations, occur frequently in patients with thymoma associated with myasthenia gravis (MG). Dissociated thymic lymphocytes from 22 of 72 MG patients secreted StrAb when cultured with PWM. A high yield of EBV-transformed B cell lines was established from thymus, thymoma, and peripheral blood of seven patients with MG, but clones secreting StrAb arose only from the three patients who had StrAb in their sera. The monoclonal StrAb bound to A bands or I bands in skeletal muscle of human, rat, and frog. One bound to mitochondria in addition to myofibrillar I bands. None bound to nuclei, smooth muscle, or gastric mucosal cells. In immunoblot analyses and ELISAs the monoclonal StrAb bound to muscle and nonmuscle isotypes of myosin, alpha actinin, and/or actin. All bound to contractile proteins common to thymus and muscle, and one selectively immunostained epithelial cells of the thymic medulla. From these antigenic specificities we suggest that StrAb might arise as an immune response directed against the cytoskeletal anchoring proteins associated with nicotinic acetylcholine receptors in thymic epithelial cells undergoing neoplastic transformation to thymoma.
Functional Characterization of the Sinorhizobium meliloti Acetate Metabolism Genes aceA, SMc00767, and glcB

ABSTRACT The genes encoding malate synthase (glcB) and isocitrate lyase (aceA) and a 240-bp open reading frame (SMc00767) located downstream of aceA were isolated and functionally characterized in Sinorhizobium meliloti. Independent and double interposon mutants of each gene were constructed, and the corresponding phenotypes were analyzed. aceA mutants failed to grow on acetate, and mutants deficient in SMc00767 were also affected in acetate utilization. In contrast, mutants deficient in glcB grew on acetate similar to wild-type strain Rm5000. Complementation experiments showed that aceA and SMc00767 gene constructs were able to restore the growth on acetate in the corresponding single mutants. aceA-glcB, aceA-SMc00767, and glcB-SMc00767 double knockouts were also unable to grow on acetate, but this ability was recovered when the wild-type aceA-glcB or aceA-SMc00767 loci were introduced into the double mutants. These data confirm the functional role of aceA and SMc00767 and show that glcB, in the absence of SMc00767, is required for acetate metabolism. Isocitrate lyase and malate synthase activities were measured in strain Rm5000, the mutant derivatives, and complemented strains. aceA and glcB were able to complement the enzymatic activity lacking in the corresponding single mutants. The enzymatic activities also showed that SMc00767 represses the activity of isocitrate lyase in cells grown on acetate. Gene fusions confirmed the repressor role of SMc00767, which regulates aceA expression at the transcriptional level. Comparison of the transcriptional profiles of the SMc00767 mutant and wild-type strain Rm5000 showed that SMc00767 represses the expression of a moderate number of open reading frames, including aceA; thus, we propose that SMc00767 is a novel repressor involved in acetate metabolism in S. meliloti. Genetic and functional analyses indicated that aceA and SMc00767 constitute a functional two-gene operon, which is conserved in other α-proteobacteria. Alfalfa plants infected with the aceA and glcB mutants were not impaired in nodulation or nitrogen fixation, and so the glyoxylate cycle is not required in the Rhizobium-legume symbiosis.
Gastrointestinal Stromal Tumors: Clinical Significance of p53 Expression, MDM2 Amplification, and KIT Mutation Status

Background:Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Clinical behavior is best predicted by size and mitotic count (risk index). KIT and platelet-derived growth factor receptor &agr; (PDGFRA) mutations have therapeutic and prognostic value but few other prognostically significant molecular markers have been identified. We investigated the prognostic value of p53 protein expression and MDM2 gene amplification in a series of GISTs. Methods:Thirty-five GISTs were tested for KIT and PDGFRA mutations, p53 protein expression (high >10% positive by immunohistochemistry) and MDM2 gene amplification (ratio >1.8). Mitotic index (>5/50 HPF), MDM2 amplification status, p53 protein expression, tumor size, and KIT/PDGFRA mutational status were correlated with clinical outcome. Results:Only a single (3%) GIST was amplified for MDM2. p53 protein expression, mitotic index, and KIT/PDGFRA mutations did not correlate with recurrence or metastasis (P=0.20, 0.50, and 0.08, respectively) but tumor size did (P=0.04). Risk assessment (size and mitotic index) showed a weak association with clinical behavior (P=0.19). Conclusions:MDM2 amplification is uncommon in GISTs. Although high p53 expression occurred in 35% of cases, it did not correlate with clinical behavior. Only GIST size predicted clinical outcome.
NIM811, a Cyclophilin Inhibitor, Exhibits Potent In Vitro Activity against Hepatitis C Virus Alone or in Combination with Alpha Interferon

ABSTRACT Host factors involved in viral replication are potentially attractive antiviral targets that are complementary to specific inhibitors of viral enzymes, since resistant mutations against the latter are likely to emerge during long-term treatment. It has been reported recently that cyclosporine, which binds to a family of cellular proteins, cyclophilins, inhibits hepatitis C virus (HCV) replication in vitro. Here, the activities of various cyclosporine derivatives were evaluated in the HCV replicon system. There was a strong correlation between the anti-HCV activity and cyclophilin-binding affinity of these compounds. Of these, NIM811 has been selected as a therapeutic candidate for HCV infection, since it binds to cyclophilins with higher affinity than cyclosporine but is devoid of the significant immunosuppressive activity associated with cyclosporine. NIM811 induced a concentration-dependent reduction of HCV RNA in the replicon cells with a 50% inhibitory concentration of 0.66 μM at 48 h. Furthermore, a greater than three-log10 viral RNA reduction was achieved after treating the cells with as little as 1 μM of NIM811 for 9 days. In addition, the combination of NIM811 with alpha interferon significantly enhanced anti-HCV activities without causing any increase of cytotoxicity. Taken together, these promising in vitro data warrant clinical investigation of NIM811, an inhibitor of novel mechanism, for the treatment of hepatitis C.
Lattice array receiver and sender for spatially orthonormal MIMO communication

In this paper, line-of-sight (LoS) oriented multiple input multiple output (MIMO) communication is examined. It is shown that two opposing rectangular (as well as square and linear) lattice antenna arrays achieve the maximum attainable channel capacity, when a certain distance-wavelength condition is fulfilled. A relationship for a large number of antenna elements is derived that connects LoS MIMO with LoS SISO channel capacity, through array aperture, wavelength and number of array antenna elements. Furthermore, a sensitivity study is performed for the proposed MIMO array arrangement that reveals high robustness against various array and antenna element position errors. Sensitivity against reflections is also examined, with the conclusion that the studied MIMO scheme appears less sensitive to reflections than a SISO system.
Detection of Novel Proline 3-Hydroxylase Activities in Streptomyces and Bacillus spp. by Regio- and Stereospecific Hydroxylation of l-Proline

During the screening of microbial proline hydroxylases, novel proline 3-hydroxylase activities, which hydroxylate free l-proline to free cis-3-hydroxy-l-proline, were detected in whole cells of Streptomyces sp. strain TH1 and Bacillus sp. strains TH2 and TH3 from 3,000 strains isolated from soil. The reaction product was purified from a reaction mixture of Streptomyces sp. strain TH1, and its chemical structure was identified as cis-3-hydroxy-l-proline by instrumental analyses. Proline 3-hydroxylase activity was also detected in Streptomyces canus ATCC 12647 which produces the 3-hydroxyproline-containing peptide antibiotic telomycin. Bacillus sp. strains TH2 and TH3 were found to accumulate cis-3-hydroxy-l-proline in culture media at 426 and 352 (mu)M, respectively. It was suggested that hydroxylation occurred in a highly regio- and stereospecific manner at position 3 of l-proline because no hydroxylation product other than cis-3-hydroxy-l-proline was observed. Proline 3-hydroxylases of these strains were first characterized on crude enzyme preparations. Since 2-oxoglutarate and ferrous ion were required for hydroxylation of l-proline, these 3-hydroxylases were thought to belong to a family of 2-oxoglutarate-related dioxygenases. The reaction was inhibited by Co(sup2+), Zn(sup2+), and Cu(sup2+). l-Ascorbic acid accelerated the reaction. The optimum pH and temperature were 7.5 and 35(deg)C, respectively.
Development of Infant Reaching in the Dark to Luminous Objects and ‘Invisible Sounds’

Two studies were conducted to investigate the existence of an unusual U-shaped developmental function described by Wishart et al (1978) for human infants reaching towards invisible sounds. In study 1, 2–7 month olds were presented with four conditions: (i) an invisible auditory stimulus alone, (ii) a glowing visual stimulus alone, (iii) auditory and visual stimuli on the same side (ie combined), and (iv) auditory and visual stimuli on opposite sides (ie in conflict). Study 2 was designed to examine the effects of practice and possible associations made when using the ‘combined conflict’ paradigm. Infants of 5 and 7 months of age were given five trials with the auditory stimulus, with or without prior visual experience, and five trials with the visual stimulus, with the position of the stimulus varied on each trial. Stimuli were presented individually at the midline, and ±30 and ±60° from the midline. In both studies testing was conducted in complete darkness. Results indicated that the auditory-alone condition was slower to elicit a reach from the infants, relative to the visual-alone one, and reaches were least frequent to the auditory target. No U-shaped function was obtained, and reaching for auditory targets occurred later in age than for visual targets, but even at 7 months of age did not occur as often and was achieved by fewer infants. In both studies the quality of the reach was significantly poorer to auditory than to visual targets, but there were some accurate reaches. This research adds to our understanding of the development of auditory — manual coordination in sighted infants and is relevant to theories of auditory localization, visually guided reaching, and programming for the blind.
Donor Pretreatment with Tetrahydrobiopterin Saves Pancreatic Isografts from Ischemia Reperfusion Injury in a Mouse Model

Depletion of the nitric oxide synthase cofactor tetrahydrobiopterin (H4B) during ischemia and reperfusion is associated with severe graft pancreatitis. Since clinically feasible approaches to prevent ischemia reperfusion injury (IRI) by H4B‐substitution are missing we investigated its therapeutic potential in a murine pancreas transplantation model using different treatment regimens. Grafts were subjected to 16 h cold ischemia time (CIT) and different treatment regimens: no treatment, 160 μM H4B to perfusion solution, H4B 50 mg/kg prior to reperfusion and H4B 50 mg/kg before recovery of organs. Nontransplanted animals served as controls. Recipient survival and endocrine graft function were assessed. Graft microcirculation was analyzed 2 h after reperfusion by intravital fluorescence microscopy. Parenchymal damage was assessed by histology and nitrotyrosine immunohistochemistry, H4B tissue levels by high pressure liquid chromatography (HPLC). Compared to nontransplanted controls prolonged CIT resulted in significant microcirculatory deterioration. Different efficacy according to route and timing of administration could be observed. Only donor pretreatment with H4B resulted in almost completely abrogated IRI‐related damage showing graft microcirculation comparable to nontransplanted controls and restored intragraft H4B levels, resulting in significant reduction of parenchymal damage (p < 0.002) and improved survival and endocrine function (p = 0.0002 each). H4B donor pretreatment abrogates ischemia‐induced parenchymal damage and represents a promising strategy to prevent IRI following pancreas transplantation.
Induction of apoptosis in ovarian carcinoma cells by AHPN/CD437 is mediated by retinoic acid receptors

Retinoids have great promise in the area of cancer therapy and chemoprevention. These natural and synthetic derivatives of vitamin A have been shown to play an important role in regulating cell differentiation and proliferation. While all‐trans‐retinoic acid (ATRA) has been demonstrated to inhibit the growth of several ovarian tumor cell lines, other ovarian carcinoma cell lines have been found to be resistant to retinoid dependent growth suppression. Interestingly, a novel synthetic retinoid, CD437 or AHPN, has been demonstrated to inhibit the growth of both ATRA‐sensitive (CA‐OV3) and ATRA‐resistant (SK‐OV3) ovarian tumor cell lines as well as to induce apoptosis. The overall goal of this research was to understand the mechanism by which AHPN/CD437 induces apoptosis in ovarian tumor cell lines. Since a number of studies have demonstrated the importance of nuclear receptors (RARs and RXRs) in mediating cellular responses to retinoids, we wished to determine the role of RARs in mediating the AHPN/CD437 response. We modulated RAR level and function by overexpressing either wild type RAR‐γ or a pan dominant negative mutant of all RAR subtypes called RAR‐β (R269Q), or through the use of an RAR‐γ antagonist, MM11253. We found that inhibition of RAR function reduced but did not eliminate induction of apoptosis in both CA‐OV3 and SK‐OV3 cells by AHPN/CD437. Likewise, overexpression of wild type RAR‐γ was found to increase apoptosis after treatment with AHPN/CD437. Our results suggest that in ovarian carcinomas, AHPN/CD437 induced apoptosis is mediated at least in part via an RAR pathway. J. Cell. Physiol. 185:61–67, 2000. © 2000 Wiley‐Liss, Inc.
Cognitive changes in very old persons with dementia: the influence of demographic, psychometric, and biological variables.

Longitudinal changes in global cognitive functioning, indexed by the Mini-Mental State Examination (MMSE), in subjects with dementia (Alzheimer's disease and vascular dementia) were examined. The roles of several demographic, psychometric, and biological indices in predicting cognitive deterioration were also examined. The sample consisted of 36 very old (M age at entry = 83.0 years, range = 75-95) adults with dementia from a community-based study. Subjects were tested on two occasions separated by approximately 2.5 years. Results indicated significant longitudinal decline in MMSE scores over the retest interval; the average decline was estimated as 2.43 (SD = 1.81) points per year. Several factors were associated with cognitive deterioration. Higher initial MMSE scores were associated with greater deterioration, whereas superior forward digit span and Block Design at entry were associated with attenuated decline, once differences in baseline severity were accounted for. By contrast, a variety of other putatively important variables exhibited no relationship to decline, including age, gender, education, onset age, dementia type, backward digit span, as well as a number of biological parameters (e.g., vitamin B12, folic acid). The results suggest that although the magnitude of cognitive deterioration in dementia is highly variable, several indicators may be useful predictors of future changes in cognitive functioning.
Multimodal prediction of dementia with up to 10 years follow up: the Gothenburg MCI study.

BACKGROUND Neuropsychological tests, CSF Aβ42, T-tau, P-tau181, hippocampal volume, and white matter lesions have been shown to predict conversion to dementia in patients with mild cognitive impairment (MCI). OBJECTIVE To examine the predictive value of combinations of these markers and to examine if the absence of pathological markers provides a lasting reduction of conversion rates. METHODS The Gothenburg MCI study is a clinically based study. Seventy-three MCI patients were included in the present sub-study and followed for a maximum of ten years. Thirty-four patients converted to dementia (18 to AD) and 39 remained stable. At inclusion, patients were classified into positive or negative risk groups according to results from neuropsychological testing (Rey auditory verbal learning test, Boston naming test, Trail making test B), CSF biomarkers (amyloid β42, T-tau, and P-tau181), and MRI scans (hippocampal volume, white matter lesions). RESULTS Trail making test B (TMT-B) was the best single predictor for the prediction of dementia (AUC 0.89, HR 25), and T-tau was the best predictor of AD (AUC 0.97, HR 41). The combination of hippocampal volume and TMT-B was the best combination for the prediction of dementia (HR 25), and the combination of hippocampal volume and T-tau was the best combination for the prediction of AD (HR 37). CONCLUSION Neuropsychological tests, CSF markers, and hippocampal volume predicted conversion from MCI to AD and general dementia. The absence of pathological markers provided a long-time protection from dementia.
Analysis of the Serum Levels of Fungi-Specific Immunoglobulin E in Patients with Allergic Diseases

Background: Atopic patients are exceptionally sensitive to airborne allergens. Sensitization to fungal allergens may be associated with respiratory allergic disease (RAD) and atopic dermatitis (AD). This study investigates the relationship between sensitization to different fungal allergens and the clinical manifestations of atopic disease. Methods: We retrospectively reviewed the medical records of atopic patients from the National Taiwan University Hospital from 2004 to 2009. A total of 133 atopic patients were found who were sensitive to at least 1 of the 3 most common fungi (Candida albicans, Aspergillus fumigatus, Penicillium chrysogenum) in Taiwan and were enrolled in the study. These patients were further divided into subgroups of isolated AD, isolated RAD and AD + RAD. The association between sensitization to fungi and allergic disease was analyzed by logistic regression analysis. Results: The sensitization rate to Candida-specific IgE was 81.2%, followed closely by Aspergillus at 69.2% and Penicillium at 63.2%. Isolated AD was the most common diagnosis. The levels of specific IgE antibodies against Aspergillus, Candida and Penicillium were highest in patients with isolated AD. Logistic regression revealed that isolated AD was highly associated with sensitization to Candida [odds ratio (OR) 10.45, 95% confidence interval (CI) 2.37–45.9]. In contrast, sensitization to Penicillium (OR 0.34, 95% CI 0.13–0.87)and Candida (OR 0.30, 95% CI 0.10–0.92) showed a negative association with isolated RAD. Conclusions: Fungal sensitization is more closely associated with AD than RAD. Our results suggest that specific sensitization to fungal allergensplays a critical role in the pathogenesis of atopic disease.
Differences in clinical manifestations of genital chlamydial infections related to serovars.

OBJECTIVES: To study the association of serovars of Chlamydia trachomatis with clinical manifestations of genital tract infection and socio-demographic characteristics. METHODS: In 1986-88 the C trachomatis isolates from 159 heterosexual men and 116 women attending a sexually transmitted disease (STD) clinic were collected and typed accordingly. A medical history was recorded, a physical examination took place and samples were taken for laboratory diagnostics. RESULTS: Serovars E, F and D were the most common for both men (75%) and women (67%). Men infected with serovars of the C-complex had more often a history of STD (p = 0.06). The opposite was demonstrated in women (p = 0.07). In addition, women younger than 18 years at first intercourse were more often infected with C-complex serovars (p = 0.05). For men, the serovars F/G less often produced symptoms of urethral discharge (p = 0.01) than the serovars of the B-complex and C-complex and were less often associated with the presence of 10 or more leukocytes in a Gram-stained smear (p = 0.04). CONCLUSIONS: In this study, infections with serovars F and G caused less obvious symptoms and signs of inflammation in men; in women no differences were found in the clinical manifestation of infections with different serovars.