Miracle-dz/UniFAR-FTUs huggingface dataset:
Variations in Intralipid Tolerance in Newborn Infants

Summary: Intravenous Intralipid tolerance tests (IVLTT) were done in 26 newborn infants of 26–40 wk gestational ages. The clearance constants (k2) ranged from 1.2–12.7 (%/min) after bolus injections given within 4.5 h (n = 12) or daily (n = 13). Significant variation (17–31%) occurred, similar to adults, and was unrelated to the time or dose given. Eleven infants received continuous Intralipid infusions for 10–24 h at a rate calculated to maintain a plasma Intralipid plateau concentration of 100 mg/dl. Nine infants did not exceed this optimal plasma level, although four could have tolerated more Intralipid. Two infants exceeded the ideal plasma concentration (> 100 mg/dl). All infants achieved and maintained plateaus within 5 h. Neither day-to-day variations nor the bolus dose used to establish clearance characteristics, accounted for the discrepancies in plateaus achieved. These studies identify some limitations of the IVLTT as a predictor of Intralipid utilization during continuous infusion, and the need for early monitoring of plasma Intralipid concentrations to optimize the therapeutic dose given to newborn infants.
Intracellular Processing of Metalloprotease Disintegrin ADAM12*

ADAM12 has been implicated in cell-cell interactions in myogenesis and cancer, but the structure of the mature form of ADAM12 is not known, and its localization on the cell surface has been questioned. In this report, we show that full-length ADAM12 isN-glycosylated in the endoplasmic reticulum (ER) and proteolytically processed in the trans-Golgi network to an ∼90-kDa form. The ∼90-kDa form, which lacks the prodomain, was the predominant form present at the cell surface. Replacement of Leu73 in the putative α-helical region in the prodomain with proline resulted in retention of ADAM12 in the ER and a complete lack of its processing. However, deletion of the entire pro- and metalloprotease domains did not affect the processing and trafficking of ADAM12. In contrast, replacement of the cytoplasmic domain of ADAM12 with that of ADAM9 or adding a c-Myc tag at the C terminus led to a significant increase in transport of the protein to the cell surface. These results suggest that the cytoplasmic domain of ADAM12 plays an important role in regulating ADAM12 exit from the ER. We conclude that properly folded mouse ADAM12, after passing a rate-limiting step of exit from the ER, is processed in the secretory pathway and reaches the cell surface, where it can mediate adhesion-mediated signaling.
Mos stimulates MAP kinase in Xenopus oocytes and activates a MAP kinase kinase in vitro

Several protein kinases, including Mos, maturation-promoting factor (MPF), mitogen-activated protein (MAP) kinase, and MAP kinase kinase (MAPKK), are activated when Xenopus oocytes enter meiosis. De novo synthesis of the Mos protein is required for progesterone-induced meiotic maturation. Recently, bacterially synthesized maltose-binding protein (MBP)-Mos fusion protein was shown to be sufficient to initiate meiosis I and MPF activation in fully grown oocytes in the absence of protein synthesis. Here we show that MAP kinase is rapidly phosphorylated and activated following injection of wild-type, but not kinase-inactive mutant, MBP-Mos into fully grown oocytes. MAP kinase activation by MBP-Mos occurs within 20 min, much more rapidly than in progesterone-treated oocytes. The MBP-Mos fusion protein also activates MPF, but MPF activation does not occur until approximately 2 h after injection. Extracts from oocytes injected with wild-type but not kinase-inactive MBP-Mos contain an activity that can phosphorylate MAP kinase, suggesting that Mos directly or indirectly activates a MAPKK. Furthermore, activated MBP-Mos fusion protein is able to phosphorylate and activate a purified, phosphatase-treated, rabbit muscle MAPKK in vitro. Thus, in oocytes, Mos is an upstream activator of MAP kinase which may function through direct phosphorylation of MAPKK.
Sex-Specific Gene Expression During Meiotic Prophase I: Xlr (X Linked, Lymphocyte Regulated), Not Its Male Homologue Xmr (Xlr Related, Meiosis Regulated), Is Expressed in Mouse Oocytes

Abstract The Xmr (Xlr related, meiosis regulated) gene product is abundantly expressed in primary spermatocytes and is notably associated with nonrecombining segments of sex chromosomes in the XY body. Here we determined whether Xmr was expressed in meiotic oocytes. This was done by reverse transcription-polymerase chain reaction and cDNA sequencing, Western blot analysis, and immunocytochemistry. Unexpectedly, no Xmr message was detected in mouse fetal oocytes. Instead, Xlr (X linked, lymphocyte regulated), a closely related gene expressed in fetal thymus cells at the time of antigen-receptor gene rearrangement, was expressed in oocytes throughout meiotic prophase I. These findings indicate a sex-specific expression of two closely related members of the Xlr gene family during meiotic prophase I. The XLR protein may provide a useful marker for studies on chromatin condensation or DNA recombination in oocytes. In addition, because of the localization of the Xlr sequence family on the mouse X chromosome, the human equivalent of Xlr is a candidate gene for premature ovarian failure.
Ratios of leptin to insulin and adiponectin to endothelin are sex-dependently associated with extent of coronary atherosclerosis

Abstract Objective: Noninvasive diagnostics of early stages of coronary artery disease and discrimination between various extents of vascular lesions in patients is an important clinical problem especially considering wide spread use of cholesterol lowering drugs that affect lipid and lipoprotein profiling. The main goal of our study was to evaluate applicability of new combinations of noninvasive biomarkers such as leptin to insulin and adiponectin to endothelin ratios, for detection of early stages of coronary atherosclerosis versus later stages of the disease. Patients and methods: A number of previously validated serum biomarkers were tested in a group of 500 patients with coronary artery disease and examined for their association with severity of coronary lesion according to Gensini score determined by coronary angiography. Results: Lowest extent of coronary lesions was associated with significant increase in apoA-I levels and with significantly increased ratios of adiponectin to endothelin and leptin to insulin. In male but not in female patients, adiponectin to endothelin ratio below 7.0 was associated with Gensini score representing early to high coronary lesions (p = 0.02). In female but not in male patients, leptin to insulin ratio below 3.5 was associated with Gensini score representing early to high coronary lesions (p = 0.013). Conclusion: Leptin to insulin and adiponectin to endothelin ratios are novel derived biomarkers useful for noninvasive diagnostics of initial stages of coronary lesions in patients with coronary artery disease.
A 57-to-64-GHz 0.094-mm2 5-bit Passive Phase Shifter in 65-nm CMOS

This paper presents the design of a compact 60-GHz phase shifter that provides a 5-bit digital phase control and 360° phase range for beam-forming systems. The phase shifter is designed using the proposed cross-coupled bridged T-type topology and switched-varactor reflective-type topology. The topologies are analyzed using a small-signal equivalent circuit model. Furthermore, the design equations are derived and investigated. To validate the theoretical analysis, 60-GHz 5-bit 360° phase shifters are designed in a commercial 65-nm CMOS technology. The fabricated 360° phase shifter features good performance of 32 phase states from 57 to 64 GHz with an rms phase error of 4.4°, a total insertion loss of 14.3 ± 2 dB, an rms gain error of 0.5 dB, P1 dB of better than 9.5 dBm, and the power consumption of almost zero. To the best of our knowledge, the designed 360° phase shifter with the size of 0.094 mm2 is the smallest 5-bit passive phase shifter at frequencies around 60 GHz.
Increased Retinal Thinning after Combination of Internal Limiting Membrane Peeling and Silicone Oil Endotamponade in Proliferative Diabetic Retinopathy

Background: The aim of this study was to examine the change in retinal thickness after vitrectomy with internal limiting membrane (ILM) peeling and/or silicone oil (SO) endotamponade in proliferative diabetic retinopathy (PDR). Methods: The actual amount and ratio of changes in the retinal thickness were calculated. Results: Compared to control eyes in the ILM peeling (-)/SO (-) group, the central, superior inner, and temporal inner retina in the ILM peeling (+)/SO (-) group, the central and superior inner retina in the ILM peeling (-)/SO (+) group, and the central, inferior inner, temporal inner, and nasal inner retina in the ILM peeling (+)/SO (+) group showed a significant reduction of the retinal thickness. The central, superior inner, and temporal inner retina in the ILM peeling (+)/SO (-) group, the central and superior inner retina in the ILM peeling (-)/SO (+) group, and the central, superior inner, inferior inner, and temporal inner retina in the ILM peeling (+)/SO (+) group showed a significantly increased reduction rate of the retinal thickness compared to the control group. Conclusions: Macular retinal thinning in PDR was observed after ILM peeling and SO endotamponade, and it was increased by the combination of these 2 factors.
[Effect of STAT5 gene silencing on the proliferation of T lymphocytes in a mouse model of asthma].

OBJECTIVE To study the effect of silencing STAT5 gene on the proliferation of T lymphocytes in a mouse model of asthma. METHODS Spleen T-lymphocytes of normal and asthmatic mice were selected by immunomagnetic beads, and the STAT5a/b genes of these T-lymphocytes were silenced by siRNA. The mRNA of STAT5a/b was detected by fluorescence quantitative PCR, and the protein by Western blot. The proliferation rates of T-lymphocytes was evaluated by CCK-8, and the cell cycle and the cell apoptosis was measured by flow cytometry. RESULTS (1) Significant inflammatory cell infiltration was present in asthmatic mouse airways, as compared to the normal control mice. (2) The STAT5a/b mRNA expression of the asthmatic group was significantly higher compared with the normal control group. (3) Compared to the blank control group, the mRNA expression of STAT5a/b was reduced in the siRNA-specific intervention (T: 35.014 vs 14.553, P < 0.01). The protein expression of STAT5a/b was also reduced after siRNA-specific intervention (T: -10.958 vs -14.706, P < 0.01). The proliferation rates of T lymphocytes was reduced after siRNA-specific intervention (T: 8.692 vs 10.540, P < 0.01), and the number of T-lymphocytes in proliferative phase was all significantly reduced after siRNA-specific intervention (T: 6.975 vs -5.567, P < 0.05). The apoptosis rates of T lymphocytes were significantly increased after siRNA-specific intervention (T: -6.404 vs -6.038, P < 0.05). CONCLUSION RNA interference specifically reduced the expression of STAT5a/b, inhibited the proliferation of T lymphocytes, and promoted the apoptosis of T lymphocytes in a mouse model of asthma.
Molecular analysis of the polymorphisms of thymidylate synthase on cell‐free circulating DNA in blood of patients with advanced colorectal carcinoma

As a key enzyme in folate metabolism, the thymidylate synthase (TS) is important for the synthesis of nucleotides. Its polymorphisms may affect the TS gene expression and the susceptibility for Fluoropyrimidine (FU)‐based chemotherapies. In this study, we assessed the relationship between the TS genotypes and clinical outcome to 5‐FU‐based chemotherapy, and examined whether cell‐free circulating DNA is applicable for these molecular analyses. We combined the variable number tandem repeat (VNTR) and single nucleotide (SNP) polymorphisms of the TS promoter and the deletion variants (1494del6) in the 3′UTR with the occurrence of loss of heterozygosity (LOH) at the microsatellite markers D18S59, D18S1140, and D18S976 mapped up‐ and downstream to the TS locus. Cell‐free blood DNA, tumor tissues, and leukocytes of 51 patients with advanced colorectal cancer were used. Genotyping revealed linkage disequilibrium between TS promoter and 3′UTR (p = 0.03) in blood and leukocytes. Inverse associations of the response to therapy with the number of polymorphisms (p = 0.05) and the 494del6 polymorphism (p < 0.02) were detected on serum DNA. The quantification of serum DNA showed significant correlations with the 1494del6 variant (p = 0.006) in tumor tissues and the combined polymorphisms in leukocytes (p < 0.04). In contrast to the low LOH frequency in blood, LOH spanned more than one marker in the primary tumor of the majority of the patients suggesting the loss of the entire TS locus. Our data provide insight into the molecular diversity of the regulation of the TS gene expression. This is the first study that compares multi‐variant TS genotypes in different clinical specimens.
Protein tyrosine phosphatase PRL-3 in malignant cells and endothelial cells: expression and function

Protein tyrosine phosphatase PRL-3 mRNA was found highly expressed in colon cancer endothelium and metastases. We sought to associate a function with PRL-3 expression in both endothelial cells and malignant cells using in vitro models. PRL-3 mRNA levels were determined in several normal human endothelial cells exposed or unexposed to the phorbol ester phorbol 12-myristate 13-acetate (PMA) and in 27 human tumor cell lines. In endothelial cells, PRL-3 mRNA expression was increased in human umbilical vascular endothelial cells and human microvascular endothelial cells (HMVEC) exposed to PMA. An oligonucleotide microarray analysis revealed that PRL-3 was among the 10 genes with the largest increase in expression on PMA stimulation. Phenotypically, PMA-treated HMVEC showed increased invasion, tube formation, and growth factor–stimulated proliferation. A flow cytometric analysis of cell surface markers showed that PMA-treated HMVEC retained endothelial characteristics. Infection of HMVEC with an adenovirus expressing PRL-3 resulted in increased tube formation. In tumor cells, PRL-3 mRNA levels varied markedly with high expression in SKNAS neuroblastoma, MCF-7 and BT474 breast carcinoma, Hep3B hepatocellular carcinoma, and HCT116 colon carcinoma. Western blotting analysis of a subset of cell line lysates showed a positive correlation between PRL-3 mRNA and protein levels. PRL-3 was stably transfected into DLD-1 colon cancer cells. PRL-3-overexpressing DLD-1 subclones were assessed for doubling time and invasion. Although doubling time was similar among parental, empty vector, and PRL-3 subclones, invasion was increased in PRL-3-expressing subclones. In models of endogenous expression, we observed that the MCF-7 cell line, which expresses high levels of PRL-3, was more invasive than the SKBR3 cell line, which expresses low levels of PRL-3. However, the MDA-MB-231 cell line was highly invasive with low levels of PRL-3, suggesting that in some models invasion is PRL-3 independent. Transfection of a PRL-3 small interfering RNA into MCF-7 cells inhibited PRL-3 expression and cell invasion. These results indicate that PRL-3 is functional in both endothelial cells and malignant cells and further validate PRL-3 as a potentially important molecular target for anticancer therapy. [Mol Cancer Ther 2006;5(2):219–29]
Tubercular Mycobacterial Spindle Cell Pseudotumour: A Case Report

Pseudotumour is a benign inflammatory lesion. Mycobacterial spindle cell pseudotumour (MSP) is a rare pseudotumour. It is a benign proliferation of spindle-shaped histiocytes containing acid-fast mycobacterium, commonly reported in immunocompromised patients. MSP is usually associated with mycobacterium avium complex (MAC). Here, we present the case of a 38-year-old gentleman with acquired immune deficiency syndrome (AIDS) who presented with low-grade fever for 1-month duration. Clinically, he had generalised lymphadenopathy. Chest X-ray showed miliary infiltration in bilateral lung fields. Lymph nodal biopsy showed spindle-shaped histiocytes filled with acid-fast bacilli on Ziehl-Neelsen (ZN) stain, suggestive of MSP. Immunohistochemical (IHC) stains were positive for CD68, S-100 and negative for CD31, which are consistent with MSP. Polymerase chain reaction (PCR) of the biopsy tissue was positive for MTB. Highly active antiretroviral therapy (HAART) was continued and anti-tubercular therapy (ATT) was started. The fever resolved within two weeks and there was a resolution of lymph nodal swelling by 6 weeks. The diagnosis of MSP associated with mycobacterium tuberculosis (MTB) makes our case interesting. It is of utmost importance to differentiate MSP from Kaposi’s sarcoma (KS) and other pseudotumours and to know whether it is of tubercular or non-tubercular origin, as the treatment is entirely different.
Contractile responses of cultured bovine retinal pericytes to angiotensin II.

OBJECTIVE To document that angiotensin (ANG) II contracts cultured bovine retinal pericytes via saralasin-sensitive receptors if the cells are prerelaxed. METHODS Changes in the contractile tone were quantified as the changes in the summed length of wrinkles induced by pericytes cultured on the silicone surface. RESULTS Angiotensin II (10(-5) mol/L) did not increase the contractile tone of cultured pericytes that were not prerelaxed. However, when the pericytes had been prerelaxed 41% with 10(-6)-mol/L sodium nitroprusside, ANG II at the range of 10(-7) to 10(-5) mol/L caused prompt, dose-related, significant (P<.01) contraction. It induced a maximum contraction (29.9%+/-5.2% [mean+/-SE]) at 10(-6) mol/L. This effect lasted at least 10 minutes. Angiotensin II receptor antagonist saralasin (10(-6) mol/L) abolished the contractile effect of ANG II (10(-6) mol/L), although by itself it did not affect the contractile tone. CONCLUSIONS Angiotensin II contracts cultured pericytes through saralasin-sensitive ANG II receptors. If ANG II affects the contractile tone of pericytes in vivo, it may affect capillary caliber, resistance, and blood flow.
Neonatal herpes simplex virus infections: HSV DNA in cerebrospinal fluid and serum

AIM To investigate the diagnostic potential of herpes simplex virus (HSV) DNA in cerebrospinal fluid and serum; to correlate the findings with outcome in the child and with type of maternal infection. METHODS Cerebrospinal fluid and serum specimens from 36 children with verified neonatal HSV infections, diagnosed between 1973 and 1996, were examined using the polymerase chain reaction technique (PCR). RESULTS In 21 children for whom both cerebrospinal fluid and sera were available, HSV DNA was found in one or both specimens in 19 (90%). Overall, HSV DNA was found in the cerebrospinal fluid of 74% of 27 children, and in the sera of 20 out of 30 children (67%). In two children HSV DNA was not demonstrable in either serum or cerebrospinal fluid. In sequential specimens from four children, the persistence of HSV DNA after the end of intravenous treatment was associated with a poor prognosis. CONCLUSIONS These findings indicate that HSV DNA detection in CSF and serum is highly sensitive for the diagnosis of neonatal HSV infections but does not replace the detection of virus in other locations using virus isolation and antigen detection.
MORC4, a novel member of the MORC family, is highly expressed in a subset of diffuse large B‐cell lymphomas

The OX‐TES‐4 antigen originally elicited an antibody response in 50% of diffuse large B‐cell lymphoma (DLBCL) patients but not in control subjects. OX‐TES‐4 is encoded by a novel gene, MORC4, located at chromosome Xq22.3. The MORC4 protein contains a HATPase‐c domain, CW zinc finger motif, nuclear localisation signals and a nuclear matrix‐binding domain, together with a coiled‐coil region. MORC4 mRNA is widely expressed at low levels in normal tissues, showing highest expression levels in placenta and testis. mRNA levels were increased in non‐germinal centre‐derived DLBCL and Hodgkin lymphoma cell lines, compared with germinal centre‐derived DLBCL cell lines and normal B cells. Nineteen DLBCL patients (66%) expressed significantly higher levels of MORC4 mRNA than normal B cells (P = 0·0031). The differential expression of MORC4 identifies this molecule as a potential lymphoma biomarker, whose overexpression may contribute to the immunological recognition of MORC4 by a subgroup of DLBCL patients.
Assessing Relative Bioactivity of Chemical Substances Using Quantitative Molecular Network Topology Analysis

Structurally different chemical substances may cause similar systemic effects in mammalian cells. It is therefore necessary to go beyond structural comparisons to quantify similarity in terms of their bioactivities. In this work, we introduce a generic methodology to achieve this on the basis of Network Biology principles and using publicly available molecular network topology information. An implementation of this method, denoted QuantMap, is outlined and applied to antidiabetic drugs, NSAIDs, 17β-estradiol, and 12 substances known to disrupt estrogenic pathways. The similarity of any pair of compounds is derived from topological comparison of intracellular protein networks, directly and indirectly associated with the respective query chemicals, via a straightforward pairwise comparison of ranked proteins. Although output derived from straightforward chemical/structural similarity analysis provided some guidance on bioactivity, QuantMap produced substance interrelationships that align well with reports on their respective perturbation properties. We believe that QuantMap has potential to provide substantial assistance to drug repositioning, pharmacology evaluation, and toxicology risk assessment.
DNA adducts and mutagenic specificity of the ubiquitous environmental pollutant 3‐nitrobenzanthrone in Muta Mouse

3‐nitrobenzanthrone (3‐NBA) is an extremely potent mutagen in the Salmonella reversion assay and a suspected human carcinogen identified in diesel exhaust and in ambient airborne particulate matter. To evaluate the in vivo mutagenicity of 3‐NBA, we analyzed the mutant frequency (MF) in the cII gene of various organs (lung, liver, kidney, bladder, colon, spleen, and testis) in lambda/lacZ transgenic mice (Muta Mouse) after intraperitoneal treatment with 3‐NBA (25 mg/kg body weight injected once a week for 4 weeks). Increases in MF were found in colon, liver, and bladder, with 7.0‐, 4.8‐, and 4.1‐fold increases above the control value, respectively, whereas no increase in MF was found in lung, kidney, spleen, and testis. Simultaneously, induction of micronuclei in peripheral blood reticulocytes was observed. The sequence alterations in the cII gene recovered from 41 liver mutants from 3‐NBA‐treated mice were compared with 32 spontaneous mutants from untreated mice. Base substitution mutations predominated for both the 3‐NBA‐treated (80%) and the untreated (81%) groups. However, the proportion of G:C→T:A transversions in the mutants from 3‐NBA‐treated mice was higher (49% vs. 6%) and the proportion of G:C→A:T transitions was lower than those from untreated mice (10% vs. 66%). The increase in MF in the liver was associated with strong DNA binding by 3‐NBA, whereas in lung, in which there was no increase in MF, a low level of DNA binding was observed (268.0–282.7 vs. 8.8–15.9 adducts per 108 nucleotides). DNA adduct patterns with multiple adduct spots, qualitatively similar to those formed in vitro after activation of 3‐NBA with nitroreductases and in vivo in rats, were observed in all tissues examined. Using high‐pressure liquid cochromatographic analysis, we confirmed that all major 3‐NBA‐DNA adducts produced in vivo in mice are derived from reductive metabolites bound to purine bases (70–80% with deoxyguanosine and 20–30% with deoxyadenosine in liver). These results suggest that G:C→T:A transversions induced by 3‐NBA are caused by misreplication of adducted guanine residues through incorporation of adenine opposite the adduct (A‐rule). Environ. Mol. Mutagen. 43:186–195, 2004. © 2004 Wiley‐Liss, Inc.