Miracle-dz/UniFAR-FTUs huggingface dataset:
Nucleolin Associates with the Human Cytomegalovirus DNA Polymerase Accessory Subunit UL44 and Is Necessary for Efficient Viral Replication

ABSTRACT In the eukaryotic cell, DNA replication entails the interaction of multiple proteins with the DNA polymerase processivity factor PCNA. As the structure of the presumptive human cytomegalovirus (HCMV) DNA polymerase processivity factor UL44 is highly homologous to that of PCNA, we hypothesized that UL44 also interacts with numerous proteins. To investigate this possibility, recombinant HCMV expressing FLAG-tagged UL44 was generated and used to immunoprecipitate UL44 and associated proteins from infected cell lysates. Unexpectedly, nucleolin, a major protein component of the nucleolus, was identified among these proteins by mass spectrometry and Western blotting. The association of nucleolin and UL44 in infected cell lysate was confirmed by reciprocal coimmunoprecipitation in the presence and absence of nuclease. Western blotting and immunofluorescence assays demonstrated that the level of nucleolin increases during infection and that nucleolin becomes distributed throughout the nucleus. Furthermore, the colocalization of nucleolin and UL44 in infected cell nuclei was observed by immunofluorescence assays. Assays of HCMV-infected cells treated with small interfering RNA (siRNA) targeting nucleolin mRNA indicated that nucleolin was required for efficient virus production, viral DNA synthesis, and the expression of a late viral protein, with a correlation between the efficacy of knockdown and the effect on virus replication. In contrast, the level of neither global protein synthesis nor the replication of an unrelated virus (reovirus) was reduced in siRNA-treated cells. Taken together, our results indicate an association of nucleolin and UL44 in HCMV-infected cells and a role for nucleolin in viral DNA synthesis.
Fertility among female hodgkin lymphoma survivors attempting pregnancy following ABVD chemotherapy

Although ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy is infrequently associated with premature amenorrhea, little is known about the success rate of women attempting pregnancy following ABVD. In the present study females treated for HL with ABVD chemotherapy without pelvic radiation therapy (RT) and who were alive without relapse ≥3 years after treatment were identified from a clinical database and screened for inclusion. Using a standardized questionnaire, we determined the pregnancy rate (i.e. time‐to‐pregnancy, TTP) among survivors who had become pregnant, tried to become pregnant, or who had been sexually active for over 2 months without using contraception at any time following ABVD. The cumulative incidence of pregnancy was calculated using the Kaplan–Meier method. Cox proportional hazards models were constructed to compare the pregnancy rate among HL survivors to that reported by friend or sibling controls. Thirty‐six female HL survivors, who had attempted pregnancy after ABVD treatment, and 29 controls, completed the survey. Eighteen patients (50%) received 2–4 cycles of ABVD, 16 (44%) received 4–6 cycles, and 2 (6%) received >6 cycles. The median TTP among both HL survivors and controls was 2.0 months. The 12‐month pregnancy rates were 70% and 75%, respectively. The fertility ratio (FR) for HL survivors versus controls was 0.94 (95%CI = 0.53–1.66; p = 0.84) after adjusting for age and frequency of intercourse (where FR < 1 indicates subfertility). Age at treatment and the number of cycles of chemotherapy were not associated with pregnancy rate among HL survivors. Female HL patients who had survived without recurrence ≥3 years and who had attempted pregnancy after ABVD did not experience significant sub‐fertility. Copyright © 2006 John Wiley & Sons, Ltd.
The significance of Epstein—Barr virus seropositivity in multiple sclerosis patients?

The objective of this study was to evaluate and investigate the significance of the previously found 100% seropositivity toward Epstein–Barr virus (EBV) found in multiple sclerosis (MS) patients in contrast to healthy controls. Using a commercially available ELISA‐test (Biotest), which differentiates infections with EBV into previous infections, primary infections, reactivated infections and no previous infection, we found 137 of 138 MS patients and 124 of 138 healthy controls seropositive. A primary infection in 4 of the 124 EBV seropositive healthy controls in contrast to no primary infections in the MS EBV seropositive group was significant (P=0.049652, Fishers exact test). This may be suggestive of a lack of primary infections in MS patients, and thus strengthens the idea that MS patients are infected with EBV before development of MS. Further studies are in progress to analyse whether EBV infection is a prerequisite for the development of this disease.
Laryngeal carcinoma: experience in Ile-Ife, Nigeria.

OBJECTIVES This study aimed to determine the prevalent age, pattern of presentation, histopathology type, and outcome of management of laryngeal carcinoma in our environment. DESIGN AND SETTING This was a 10-year retrospective study carried out at a teaching hospital. MATERIALS AND METHODS Records of patients managed for laryngeal carcinoma from January 1994 to December 2004 were reviewed. Only 13 cases with tissue diagnosis were included in this review. The age, sex, occupation, presentation, use of cigarette and alcohol, investigations, histology, outcome of management, and duration of follow-up were extracted and analyzed. RESULTS The patients had a mean age of 69.9 years (range 38-88 years) and a male-to-female ratio of 12:1. Histopathology was squamous cell carcinoma in all. Symptoms included hoarseness in voice and breathlessness in all, cough in 7 (53.8%), weight loss in 7 (53.8%), and otalgia in 6 (46.2%). Two patients indulged in alcohol and two were also regular cigarette smokers. All the patients presented with stage IV disease and in respiratory distress necessitating emergency tracheostomy. Seven (53.8%) patients had total laryngectomy plus postoperative radiotherapy while 2 (15.4%) had pharyngolaryngectomy, thyroidectomy, radical neck dissection plus postoperative radiotherapy and thyroxine supplement. Surgical complications included pharyngocutaneous fistula in 2 (15.4%) patients, pharyngeal stenosis, stomal stenosis, and hypocalcemia with hypothyroidism in 1 patient each. The fistulae were managed conservatively and prognosis was good despite late presentation. CONCLUSION Laryngeal carcinoma mainly occurs in males. Presentation is late with hoarseness in voice and breathlessness in our community. Soft-tissue neck x-ray is a useful diagnostic tool. Scarce radiotherapy centers, ignorance, local taboo, poverty, and poor recognition by primary healthcare providers have a negative impact on its management. Laryngeal carcinoma should be excluded when managing elderly patients for bronchial asthma.
Brain neuronal nitric oxide synthase neuron-mediated sympathoinhibition is enhanced in hypertensive Dahl rats

Objective To elucidate the role of central neurons containing neuronal nitric oxide synthase (nNOS neurons) in the sympathetic nervous system in hypertensive Dahl salt-sensitive (DS) rats. Design and methods Dahl rats were fed either a regular-salt (0.4% NaCl) or high-salt (8% NaCl) diet for 4 weeks. The effect of intracerebroventricular administration of S-methyl-L-thiocitrulline, a selective nNOS inhibitor, on renal sympathetic nerve activity was examined in chronically instrumented conscious DS rats. The activity and protein amount of brain nNOS was evaluated by enzyme assay and western blot analysis. The distribution and number of nNOS neurons in the brainstem were examined immunohistochemically in hypertensive and normotensive DS rats. Results S-methyl-L-thiocitrulline induced a larger increase in tonic renal sympathetic nerve activity generated before baroreflex-mediated inhibition in hypertensive DS rats than normotensive DS rats. Hypertensive DS rats showed increased nNOS activity in the brainstem, but not in the diencephalon or cerebellum. High nNOS activity was confirmed by an increase in the amount of nNOS protein. nNOS Neurons were localized in several nuclei throughout the brainstem; the dorsolateral periaqueductal gray, pedunculopontine tegmental nucleus, dorsal raphe nucleus, laterodorsal tegmental nucleus, lateral parabrachial nucleus, rostral ventrolateral medulla, nucleus tractus solitarius and raphe magnus. The number of nNOS neurons in these nuclei, except for the two raphes, was significantly greater in hypertensive than in normotensive DS rats. Conclusions These findings suggest that central nNOS-mediated sympathoinhibition may be enhanced in salt-sensitive hypertensive Dahl rats. The upregulated nNOS-mediated inhibition may occur in the central sympathetic control system generated before baroreflex-mediated inhibition.
Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen

Serological expression cloning of antigens eliciting a humoral immune response to a syngeneic mouse sarcoma identified pem (mouse placenta and embryonic expression gene) as a new member of the cancer/testis family. To identify the human homologue of pem, mouse pem sequences and pem-related expressed sequence tags from human testis were used as PCR primers for amplification using human testis cDNA. However, rather than pem, another gene, designated OY-TES-1, was isolated and found to be the human homologue of proacrosin binding protein sp32 precursor originally identified in mouse, guinea pig, and pig. OY-TES-1 maps to chromosome 12p12-p13 and contains 10 exons. Southern blot analysis suggests the presence of two OY-TES-1-related genes in the human genome. In normal tissues, OY-TES-1 mRNA was expressed only in testis, whereas in malignant tissues, a variable proportion of a wide array of cancers, including bladder, breast, lung, liver, and colon cancers, expressed OY-TES-1. Serological survey of 362 cancer patients with a range of different cancers showed antibody to OY-TES-1 in 25 patients. No OY-TES-1 sera reactivity was found in 20 normal individuals. These findings indicate that OY-TES-1 is an additional member of the cancer/testis family of antigens and that OY-TES-1 is immunogenic in humans.
DNA interaction and cytostatic activity of the new liver organotropic complex of cisplatin with glycocholic acid: Bamet‐R2

The aim of this study was to investigate the ability of the new liver organotropic complex of cisplatin with glycocholate (GC), Bamet‐R2, to interact with DNA, inhibit its replication and hence reduce tumor‐cell proliferation. Changes in the electrophoretic mobility of the open and covalently closed circular forms of the pUC18 plasmid DNA from Escherichia coli, a shift in the denaturation temperature of double‐stranded DNA, and ethidium‐bromide displacement from DNA binding, were induced by Bamet‐R2 and cisplatin, but not by GC. Neutral‐red retention was used to measure the number of living cells in culture after long‐term (72‐hr) exposure to these compounds and to evaluate the effect on cell viability after short‐term (6‐hr) exposure. Bamet‐R2 and cisplatin, but not GC, induced significant inhibition of cell growth. This effect ranged from mild to strong, depending upon the sensitivity of the different cell types as follows: cisplatin, rat hepatocytes in primary culture < rat hepatoma McA‐RH7777 cells (rH) < human colon carcinoma LS 174T cells (hCC) < mouse hepatoma Hepa 1–6 cells (mH); Bamet‐R2, rat hepatocytes < mH ≈ hCC < rH. DNA synthesis was measured by radiolabeled‐thymidine incorporation into DNA. Bamet‐R2 and cisplatin, but not GC, significantly inhibited the rate of DNA synthesis by these cells. After short‐term exposure to Bamet‐R2 or GC, no acute cell toxicity was observed, except on hCC cells. By contrast, acute toxicity was induced by cisplatin for all cell types studied. The in vivo anti‐tumoral effect was investigated in 3 different strains of mice following s.c. implantation of tumor cells (mouse sarcoma S‐180II cells in Swiss and B6 mice and hCC cells in nude mice). In all 3 models, tumor growth was inhibited by Bamet‐R2 and cisplatin to a similar degree. However, signs of toxicity (increases in blood urea concentrations and decreases in packed blood cell volume and in liver, kidney and body weight) and a reduction in survival rate were observed only during cisplatin administration. In sum, these results indicate that this bile‐acid derivative can be considered as a cytostatic drug whose potential usefulness deserves further investigation. Int. J. Cancer 78:346–352, 1998. © 1998 Wiley‐Liss, Inc.
CD11chighCD8+ Regulatory T Cell Feedback Inhibits CD4 T Cell Immune Response via Fas Ligand–Fas Pathway

Regulatory T cells can restrict the uncontrolled immune response and inflammation, avoiding pathologic immune injury to the host and thus playing important roles in the maintenance of immune homeostasis. Until recently, many subsets of CD4 and CD8 regulatory T cells have been reported. In this study, we identified CD11chighCD8+ T cells as a new subset of CD8+ regulatory T cells. During Listeria monocytogenes and Staphylococcus aureus infection, two subsets of CD8 T cells were classified according to the expression level of CD11c, including CD11clowCD8+ and CD11chighCD8+ T cells. CD11clowCD8+ T cells, existing during the whole period of infection, act as conventional activated T cells to kill target cells in a perforin-dependent manner. Interestingly, CD11chighCD8+ T cells appeared only at a late stage of infection, expressed relatively high CD122 and low CD69, did not secrete IFN-γ, IL-10, TGF-β, and exhibited much more potent cytotoxicity against target cells via Fas ligand–Fas pathway in an Ag-independent manner. Ligation of CD11c was important in the cytotoxicity of CD11chighCD8+ T cells. Furthermore, CD11chighCD8+ T cells could directly kill the activated CD4 T cells both in vitro and in vivo, whereas CD11clowCD8+ T cells could not. Thus, we identified an infection-induced new subset of CD11chighCD8+ regulatory T cells, which might contribute to protect host from pathological immune injure. Our results indicate that CD11c+CD8+ T cells are constitute a heterogeneous population that can be divided further into regulatory CD11chighCD8+ T cell subset and effector CD11clowCD8+ T cell subset, thus adding insight to the role of CD8 T cells in immune response and regulation.
Erythrocyte ageing in vivo and in vitro: structural aspects and implications for transfusion

summary Erythrocyte transfusion is essential in conditions of large blood loss, of inadequate bone marrow production and of increased erythrocyte breakdown. The structural and biochemical changes that erythrocytes go through during storage, probably associated with the disappearance of up to 30% of the erythrocytes within 24 h after transfusion, are likely to contribute to the transfusion side effects: iron overload, erythrocyte adhesion to the endothelial surface with proinflammatory consequences, autoantibody formation, endothelial damage by released erythrocyte constituents, a hampered microcirculation and oxygen delivery. In vivo, senescent erythrocytes are marked for removal by binding of autologous immunoglobulin G to ageing antigens, which arise by changes in the conformation of the membrane domain of band 3. Also, vesicle formation has been described as an integral part of the erythrocyte ageing process. Comparable changes occur during erythrocyte storage. This review describes the current state of knowledge of the mechanism of erythrocyte ageing in vivo, ageing‐related changes occurring during erythrocyte storage in blood bank conditions and their possible relation with the transfusion side effects. In view of the key position of band 3 in the maintenance of erythrocyte structure and function, elucidation of the pathways that control posttranslational modification of band 3 during storage may lead to new approaches towards maintaining ATP concentration and cellular integrity. This review concludes with the challenge to further explore the underlying processes of erythrocyte ageing in order to provide physiologically relevant tools for assessing and predicting erythrocyte homeostasis in vitro and in vivo and thereby to contribute to the development of rational transfusion protocols for various patient categories.
LUNG TUMOR LOCATION AND LYMPHOCYTE INFILTRATION IN MICE ARE GENETICALLY DETERMINED

Lung cancer is a heterogeneous disease with individual differences in histological type, rate of progression, and response to therapy. Definition of the molecular and genetic basis of specific tumor characteristics would provide a better assessment of prognosis and a basis for a more individualized therapy. Here the authors compare the quantitative and qualitative phenotypes of lung tumors in mice of O20/A and OcB-9/Dem strains subjected to 2 regimens of N-ethyl-N-nitrosourea (ENU) treatment: (1) prenatal tumor induction by a single intraperitoneal (IP) injection of 40 mg/kg body weight into pregnant females and (2) after the same prenatal induction, the progeny received on weeks 9 and 11 additional IP ENU injections. The numbers, size, and histological characteristics of tumors were determined microscopically in semiserial lung sections. Unexpectedly, the authors observed very highly significant strain differences in a novel polymorphic phenotype—peribronchial versus nonperibronchial location of lung tumors, as well as in frequency of lymphocyte infiltration. To assess the reproducibility of these genetic differences, the authors classified both tumor location and lymphocyte infiltration also in an independent set of lung tumors that were induced in these strains in experiments performed more than 10 years ago in a different mouse facility and found the same strain differences. These results indicate that these qualitative phenotypes are very robust (Pc 5.52 × 10−6 and 2.27 × 10−8, respectively) and relatively independent of environmental influences. They likely reflect different stages of lung differentiation at the time of tumor induction and differences in molecules involved in intercellular signaling, respectively. The definition of genes controlling these traits will provide novel insights into the determination of tumor phenotype.
Intraocular lens exchange through a 3.2-mm corneal incision for opacified intraocular lenses

Aim: The aim was to evaluate visual and refractive results and complications of intraocular lens (IOL) exchange through a 3.2 mm corneal incision for opacified IOLs. Materials and Methods: This retrospective study comprised 33 eyes of 32 patients with IOL opacification requiring an IOL exchange between July 2003 and March 2007. Exchange surgery was performed through a 3.2-mm temporal clear corneal incision followed by implantation of a new foldable hydrophobic IOL. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), topographical astigmatism, and refractive cylinder were evaluated. Surgically induced astigmatism (SIA) was calculated and complications were recorded. Results: Opacification was observed in 25 eyes (76%) with Aqua-Sense, 3 eyes (9%) with Hydroview, 3 eyes (9%) with MemoryLens IOLs, and 2 eyes (6%) with DgR. The mean follow-up period was 36.54 months. An uneventful IOL exchange was achieved in 18 eyes (55%). Zonular dehiscence occurred in 9 eyes (27%), and posterior capsule tear developed in 4 eyes (12%). The mean preoperative BSCVA (mean ± standard deviation, decimal scale) was 0.13 ± 0.08 (mean: 20/150, range 20/2000 to 20/60) and improved to 0.63 ± 0.18 (mean: 20/32, range 20/60 to 20/20, P < 0.001). The mean SIA was 0.70 D. Seven eyes (21%) had 0.5 D or lower SIA. Conclusion: IOL exchange is a technically challenging procedure with potential risks of reversing the advantages of a prior small-incision cataract surgery. The use of a small corneal incision for IOL exchange could preserve the advantages of modern phacoemulsification surgery with acceptable SIA related to the procedure.
Hair density in African Americans.

BACKGROUND The meager data on normal hair density in humans have been gathered from a predominantly white population. Examination of scalp biopsy specimens from African Americans suggests that hair density in this group may be lower than in whites. This study was performed to quantify any differences between white and African American patients. DESIGN A retrospective case series of subjects who had undergone a biopsy of clinically healthy scalp skin. The 4-mm punch biopsy specimens were sectioned, and all follicles contained within the specimens were counted at various levels (suprabulbar, isthmus, and infundibulum) to arrive at the number and type of hairs present. SETTING Outpatient clinic in a tertiary care medical center. PATIENTS A consecutive sample of 22 African American and 12 white patients with clinically healthy scalp skin specimens that were studied and compared with previously reported data. MAIN OUTCOME MEASURES Patients' age and total number of follicles, terminal follicles, vellus follicles, terminal anagen hairs, and terminal telogen hairs. RESULTS Total hair density (number of follicles per 4-mm punch biopsy specimen) and total number of terminal follicles and terminal anagen hairs were significantly lower in African Americans (P<.001) than in whites and in a previously reported, predominantly white, population. CONCLUSIONS Hair density in African Americans is significantly lower than that in whites, which must be taken into consideration when evaluating a biopsy specimen from an African American patient. Data previously collected from white patients may not provide adequate guidance when evaluating scalp biopsy specimens from African Americans and could lead to an incorrect diagnosis.
Cholinergic, but not NMDA, receptors in the lateral entorhinal cortex mediate acquisition in trace eyeblink conditioning

Anatomical and electrophysiological studies collectively suggest that the entorhinal cortex consists of several subregions, each of which is involved in the processing of different types of information. Consistent with this idea, we previously reported that the dorsolateral portion of the entorhinal cortex (DLE), but not the caudomedial portion, is necessary for the expression of a memory association between temporally discontiguous stimuli in trace eyeblink conditioning (Morrissey et al. (2012) J Neurosci 32:5356‐5361). The present study examined whether memory acquisition depends on the DLE and what types of local neurotransmitter mechanisms are involved in memory acquisition and expression. Male Long‐Evans rats experienced trace eyeblink conditioning, in which an auditory conditioned stimulus (CS) was paired with a mildly aversive electric shock to the eyelid (US) with a stimulus‐free interval of 500 ms. Immediately before the conditioning, the rats received a microinfusion of neuroreactive substances into the DLE. We found that reversible inactivation of the DLE with GABAA receptor agonist, muscimol impaired memory acquisition. Furthermore, blockade of local muscarinic acetylcholine receptors (mACh) with scopolamine retarded memory acquisition while blockade of local NMDA receptors with APV had no effect. Memory expression was not impaired by either type of receptor blocker. These results suggest that the DLE is necessary for memory acquisition, and that acquisition depends on the integrity of local mACh receptor‐dependent firing modulation, but not NMDA receptor‐dependent synaptic plasticity. © 2015 Wiley Periodicals, Inc.