gebhart/patrepeval huggingface dataset:
Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls. (2000)

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.
Identification and Characterization of a Novel Family of Serine/Threonine Kinases Containing Two N-terminal LIM Motifs (1995)

We previously isolated human cDNA coding for LIMK1 (LIM motif-containing protein kinase-1), a putative protein kinase containing two LIM motifs at the N terminus and an unusual protein kinase domain at the C terminus. In the present study, we isolated human cDNA encoding LIMK2, a second member of a LIMK family, with a domain structure similar to LIMK1 and 50% overall amino acid identity with LIMK1. The protein kinase domains of LIMK1 and LIMK2 are unique in that they contain an unusual sequence motif Asp-Leu-Asn-Ser-His-Asn in subdomain VIB and a highly basic insert between subdomains VII and VIII. Expression patterns of LIMK1 and LIMK2 mRNAs in human tissues differ significantly. Chromosomal localization of human LIMK1 and LIMK2 genes was assigned to 7q11.23 and 22q12, respectively, by fluorescence in situ hybridization. The Myc epitope-tagged LIMK1 and LIMK2 proteins transiently expressed in COS cells exhibited serine/threonine-specific kinase activity toward myelin basic protein and histone in in vitro kinase assay. Immunofluorescence and subcellular fractionation analysis revealed that Myc-tagged LIMK1 and LIMK2 were localized mainly in the cytoplasm. The "native" LIMK1 protein endogenously expressed in A431 epidermoid carcinoma cells also exhibited serine/threonine kinase activity. The specific activity of native LIMK1 from A431 cells was apparently much higher than that of "recombinant" LIMK1 ectopically expressed in COS cells, hence, it is likely that there is a mechanism, by which native LIMK1 is activated. A 140-kDa tyrosine-phosphorylated protein (pp140) was co-immunoprecipitated with native LIMK1 form A431 cell lysates; therefore, pp140 may be a LIMK1-associated protein involved in the regulation of LIMK1 function.
Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: A study of one hundred thirty‐three cases compared with a control group (2003)

Our findings support preliminary evidence for the safety of HCQ therapy during pregnancy. This treatment probably should be maintained throughout pregnancy in patients with systemic lupus erythematosus.
HYPERLIPOFUSCINOSIS AND SUBRETINAL FIBROSIS IN STARGARDTʼS DISEASE (1995)

It is presumed that the abnormal material in the two first patients is lipofuscin and that this represents an exaggerated response of the diseased retinal pigment epithelium, possibly to a minor trauma. That material will eventually be replaced by subretinal fibrosis. The fundus appearance in the third patient is possibly the result of a similar process.
Expression of p53 protein related to the presence of human papillomavirus (HPV) DNA in genital carcinomas and precancer lesions. (1993)

The E6 protein of the high-risk human papillomavirus (HPV) types 16 and 18 is capable of complexing with the wild-type p53 tumor suppressor gene product, leading to loss of the normal p53 function as an anti-oncogene, whereas the low-risk HPV types 6 and 11 lack this binding property. The malignant potential of HPV 16 and 18 has been ascribed to this complexing of E6 with p53, which regularly leads to undetectable expression of the latter in HPV-positive lesions. To assess the role of p53 in HPV-associated genital carcinogenesis, the expression of p53 protein was studied immunohistochemically in 22 genital carcinomas and precancer lesions; 8 vulvar carcinomas, 1 VIN (vulvar intraepithelial neoplasia), 5 cervical carcinomas and 8 CIN (cervical intraepithelial neoplasia) using monoclonal antibody PAb 1801. Presence of HPV was demonstrated by PCR using HPV consensus primers, and amplified HPV-DNA was digested with the restriction enzymes giving distinct patterns for various HPV-types in gel electrophoresis. HPV-typing was confirmed by in situ hybridization with biotinylated DNA probes. Altogether, 17 of the 22 specimens (77%) showed p53 expression: 67% of the precancer lesions and 83% of carcinomas. Expression was more frequent (89%) in the vulvar than (70%) in cervical lesions. Using PCR,HPV DNA was detected in 19/22(86%) of the samples. The following HPV types were identified: HPV 6 (2 samples), HPV 11 (3 cases), HPV 16 (5 cases), HPV 33 (3 cases), and 6 contained unidentified HPV types. All HPV DNA-negative specimens showed p53 expression. Of the 19 HPV DNA-positive lesions, 5 were p53-negative, three of these being HPV 16 positive CIN lesions. The remaining two HPV 16 lesions were invasive carcinomas with a weak p53 expression. HPV 6 and 11-positive lesions showed a weak p53 expression more frequently than HPV-negative cases and HPV 33 lesions. The results indicate that p53 expression is detectable, but it is less frequent and less intense in HPV DNA-positive genital precancer lesions and carcinomas (particularly those with HPV 16 DNA) as compared with HPV DNA-negative lesions.
Rural extension and advisory services : new directions (2002)

This study is prepared as an input for the preparation of a new Vision-to-Action Strategy for World Bank support to rural development. The paper explores issues and options relating to support for agricultural extension and rural information services needed to support rural development efforts. It reviews past experience with extension investments, current trends, and issues important to future financing for agricultural extension and rural information services. Two important issues include: the public sector must continue to finance public goods extension and information services; and situation specific strategies are needed to define extension agendas. An agenda is provided for future Bank lending which recommends avoiding errors of the past while keeping extension on the agenda, funding new investments, developing new financing mechanisms, and maintaining Bank leadership.
Regulation of fungal cell wall growth: a guanine nucleotide-binding, proteinaceous component required for activity of (1----3)-beta-D-glucan synthase. (1986)

By treatment with detergent and NaCl, particulate (1----3)-beta-D-glucan synthase (EC 2.4.1.34) from Hansenula anomala or Neurospora crassa was dissociated into a "soluble fraction" and a "membrane fraction." Each fraction alone was almost inactive, but enzymatic activity could be reconstituted by mixing the two fractions and adding GTP or one of its analogs. Based on their lability to heat and to incubation with trypsin, the activity in both fractions is proteinaceous. The active component in the soluble fraction appears to bind guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]), since it was specifically protected by this nucleotide against heat inactivation and against inactivation in the presence of EDTA. Furthermore, precipitation of the soluble component with ammonium sulfate in the presence of GTP[gamma S] gave rise to a fraction that was highly active in the absence of added nucleotide, indicating either tight binding or covalent interaction between GTP[gamma S] and the soluble component. The membrane fraction probably contains the catalytic moiety, because it was partially protected against heat inactivation by the substrate, UDP-glucose. Soluble fractions that stimulated membrane fractions from H. anomala and N. crassa were obtained from several other fungi, including Saccharomyces cerevisiae. We propose that the soluble fraction contains a GTP-binding protein that modulates the biosynthesis of (1----3)-beta-D-glucan of fungal cell walls and probably has a major role in the regulation of cell wall morphogenesis.
Isolation of II-alcohol dehydrogenase of human liver: Is it a determinant of alcoholism? (1977)

HUMAN LIVER ALCOHOL DEHYDROGENASE (ALCOHOL: NAD(+) oxidoreductase, EC 1.1.1.1), homogeneous by physicochemical criteria, has been available in quantity only recently [Lange, L. G. & Vallee, B. L. (1976) Biochemistry 15, 4681-4686]. Until now, the biochemical basis of human alcohol metabolism had to be extrapolated from the properties and behavior of enzymes from other species, primarily horses and yeast. The biological determinants of human alcoholism have remained obscure, although recent evidence indicates a genetic predisposition, requiring delineation. A functionally distinct form of human liver alcohol dehydrogenase (ADH), which we have designated II-ADH, is provocative since, thus far, it seems to be unique to human beings. It has a high K(m) for ethanol and is remarkably insensitive (apparent K(I), 500 muM) to pyrazole and its derivatives, which are usually potent ADH inhibitors (K(I), 1 muM), a property that is the basis for the isolation of II-ADH. The affinity resin 4-[3-(N-6-aminocaproyl)aminopropyl]pyrazole-Sepharose binds all other known forms of ADH but not II-ADH, thereby separating it selectively by affinity chromatography. In turn, this has led to the establishment of its identity with that enzyme form which was previously known as the anodic band and characterized by a high K(m) for ethanol (20 mM at pH 7.5). The remarkable insensitivity of II-ADH to pyrazole inhibition has also permitted quantitation of its role in hepatic ethanol oxidation. At 5 mM ethanol, a saturating concentration for virtually all other forms of ADH, II-ADH contributes less than 15% to total ethanol oxidation. However, at intoxicating concentrations, e.g., 60 mM, it can account for as much as 40% of the total ethanol oxidation rate of liver, indicating a seemingly unique role for this enzyme form in ethanol elimination. Thus far, we have found the amount of II-ADH varies from liver to liver of individuals and is considerably more labile than the other molecular forms, phenomena whose inter- or independence requires further study. The isolation of human II-ADH advances efforts to recognize and understand biochemical mechanisms that may be biological determinants of alcoholism and alcohol-related disease states, now generally approached and managed largely as psychosocial disorders.
Bifunctional oligonucleotide probes synthesized using a novel CPG support are able to detect single base pair mutations (1989)

A novel multifunctional controlled pore glass, MF-CPG (Fig. 1), has been synthesized and used to incorporate 3' terminal primary aliphatic amines into synthetic oligonucleotides. MF-CPG consists of a unique succinic acid linking arm which possesses both a masked primary amine for label attachment and a dimethoxytrityl protected hydroxyl for nucleotide chain elongation. Using MF-CPG, we have devised a simple and convenient technique to attach non-radioactive labels to the 3' terminus of oligonucleotides. Bifunctional probes can then be constructed by 32P labeling the 5' terminus with T4 kinase and gamma 32P-ATP. Using such bifunctional oligonucleotide probes in conjunction with polymerase chain reaction (PCR) amplification, we were able to detect single base substitutions in a target segment of the human H-ras protooncogene employing either functionality. Our technique thus expands the potential applications for oligonucleotides as hybridization probes.
Long-Term Prognosis for Clinical West Nile Virus Infection (2004)

Relatively little is known about the long-term prognosis for patients with clinical West Nile virus (WNV) infection. We conducted a study to describe the recovery of New York City residents infected during the 1999 WNV encephalitis outbreak. Patients were interviewed by telephone on self-perceived health outcomes 6, 12, and 18 months after WNV illness onset. At 12 months, the prevalence of physical, functional, and cognitive symptoms was significantly higher than that at baseline, including muscle weakness, loss of concentration, confusion, and lightheadedness. Only 37% achieved a full recovery by 1 year. Younger age at infection was the only significant predictor of recovery. Efforts aimed at preventing WNV infection should focus on elderly populations who are at increased risk for neurologic manifestations and more likely to experience long-term sequelae of WNV illness. More studies are needed to document the long-term sequelae of this increasingly common infection.
Isolation of Lactococcus lactis nonsense suppressors and construction of a food‐grade cloning vector (1995)

Nonsense suppressor strains of Lactococcus lactis were isolated using plasmids containing nonsense mutations or as revertants of a nonsense auxotrophic mutant. The nonsense suppressor gene was cloned from two suppressor strains and the DNA sequence determined. One suppressor is an ochre suppressor with an altered tRNA(gln) and the other an amber suppressor with an altered tRNA(ser). The nonsense suppressors allowed isolation of nonsense mutants of a lytic bacteriophage and suppressible auxotrophic mutants of L. lactis MG1363. A food-grade cloning vector based totally on DNA from Lactococcus and a synthetic polylinker with 11 unique restriction sites was constructed using the ochre suppressor as a selectable marker. Selection, following electroporation of a suppressible purine auxotroph, can be done on purine-free medium. The pepN gene from L. lactis Wg2 was subcloned resulting in a food-grade plasmid giving a four- to fivefold increase in lysine aminopeptidase activity.
The CUG codon is decodedin vivoas serine and not leucine inCandida albicans (1995)

Previous studies have shown that the yeast Candida albicans encodes a unique seryl-tRNA(CAG) that should decode the leucine codon CUG as serine. However, in vitro translation of several different CUG-containing mRNAs in the presence of this unusual seryl-tRNA(CAG) result in an apparent increase in the molecular weight of the encoded polypeptides as judged by SDS-PAGE even though the molecular weight of serine is lower than that of leucine. A possible explanation for this altered electrophoretic mobility is that the CUG codon is decoded as modified serine in vitro. To elucidate the nature of CUG decoding in vivo, a reporter system based on the C. albicans gene (RBP1) encoding rapamycin-binding protein (RBP), coupled to the promoter of the C. albicans TEF3 gene, was utilized. Sequencing and mass-spectrometry analysis of the recombinant RBP expressed in C. albicans demonstrated that the CUG codon was decoded exclusively as serine while the related CUU codon was translated as leucine. A database search revealed that 32 out of the 65 C. albicans gene sequences available have CUG codons in their open reading frames. The CUG-containing genes do not belong to any particular gene family. Thus the amino acid specified by the CUG codon has been reassigned within the mRNAs of C. albicans. We argue here that this unique genetic code change in cellular mRNAs cannot be explained by the 'Codon Reassignment Theory'.
Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogénétique Hématologique study (2010)

PAX5 is the main target of somatic mutations in acute B lymphoblastic leukemia (B-ALL). We analyzed 153 adult and child B-ALL harboring karyotypic abnormalities at chromosome 9p, to determine the frequency and the nature of PAX5 alterations. We found PAX5 internal rearrangements in 21% of the cases. To isolate fusion partners, we used classic and innovative techniques (rolling circle amplification-rapid amplification of cDNA ends) and single nucleotide polymorphism-comparative genomic hybridization arrays. Recurrent and novel fusion partners were identified, including NCoR1, DACH2, GOLGA6, and TAOK1 genes showing the high variability of the partners. We noted that half the fusion genes can give rise to truncated PAX5 proteins. Furthermore, malignant cells carrying PAX5 fusion genes displayed a simple karyotype. These data strongly suggest that PAX5 fusion genes are early players in leukemogenesis. In addition, PAX5 deletion was observed in 60% of B-ALL with 9p alterations. Contrary to cases with PAX5 fusions, deletions were associated with complex karyotypes and common recurrent translocations. This supports the hypothesis of the secondary nature of the deletion. Our data shed more light on the high variability of PAX5 alterations in B-ALL. Therefore, it is probable that gene fusions occur early, whereas deletions should be regarded as a late/secondary event.
Quantitative genetic analysis of seed vigour and pre‐emergence seedling growth traits in Brassica oleracea (2000)

The ability of seeds to germinate and establish seedlings in a predictable manner under a range of conditions has a direct contribution to the economic success of commercial crops, and should therefore be considered in crop improvement. We measured traits associated with seed vigour and pre‐emergence seedling growth in a segregating population of 105 doubled haploid Brassica oleracea lines. The germination traits measured were: mean germination times for unstressed germination; germination under water stress or germination after a heat treatment; and conductivity of seed leachate. The seedling growth traits measured were: seed weight; seedling growth rate; and seedling size at the end of the exponential growth phase. There were some correlations, notably among germination traits, and between seed weight and pre‐emergence seedling growth. Heritability of the various traits was typically in the 10–15% range, with heritability of conductivity and mean germination time under water stress 25 and 24% respectively. Collectively the results indicate that germination and pre‐emergence seedling growth are under separate genetic control. Quantitative trait loci analyses were carried out on all measurements and revealed significant loci on linkage groups O1, O3, O6, O7 and O9. We suggest that genes at these loci are important in determining predictable seed germination and seedling establishment in practice.
Identification of a novel retroviral gene unique to human immunodeficiency virus type 2 and simian immunodeficiency virus SIVMAC (1988)

Human and simian immunodeficiency-associated retroviruses are extraordinarily complex, containing at least five genes, tat, art, sor, R, and 3' orf, in addition to the structural genes gag, pol, and env. Recently, nucleotide sequence analysis of human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus SIVMAC revealed the existence of still another open reading frame, termed X, which is highly conserved between these two viruses but absent from HIV-1. In this report, we demonstrate for the first time that the X open reading frame represents a functional retroviral gene in both HIV-2 and SIVMAC and that it encodes a virion-associated protein of 14 and 12 kilodaltons, respectively. We also describe the production of recombinant TrpE/X fusion proteins in Escherichia coli and show that sera from some HIV-2-infected individuals specifically recognize these proteins.
Inhibition by sulfated chitin derivatives of invasion through extracellular matrix and enzymatic degradation by metastatic melanoma cells. (1990)

We have investigated the effects of sulfated chitin derivatives and heparin on the invasion of B16-BL6 melanoma cells through reconstituted basement membrane Matrigel which contains laminin, type IV collagen, heparin sulfate proteoglycan, and entactin. 6-O-sulfated chitin (S-chitin) and 6-O-sulfated and carboxymethyl chitin (SCM-chitin) significantly inhibited the penetration of tumor cells through Matrigel in parallel with the increased degree of sulfation. However, 6-O- and N-sulfated but partially N-deacetylated chitin derivative (SCM-chitosan) and CM-chitin had no effect. SCM-chitin with a high degree of sulfation (SCM-chitin III), which exhibited fairly low levels of anticoagulant activity, was more effective than intact heparin. SCM-chitin III and heparin were also shown to block the attachment and migration of tumor cells to laminin-coated substrates, which are considered to be involved in tumor invasion. The inhibition of cell attachment and migration by SCM-chitin III and heparin is likely to depend upon their specific binding to laminin molecules (possibly the heparin-binding domain). Degradation of heparan sulfate by heparanase was inhibited by SCM-chitin III and heparin in a dose-dependent manner. Surprisingly, SCM-chitin III could inhibit type IV collagenolytic activity of tumor cells more potently than heparin. Thus, nontoxic SCM-chitin III of low anticoagulant properties may provide a promising basis for the prevention of cancer metastasis.
The Candida albicans Lanosterol 14-α-Demethylase ( ERG11 ) Gene Promoter Is Maximally Induced after Prolonged Growth with Antifungal Drugs (2004)

The azole antifungal drugs that target lanosterol 14-alpha-demethylase, encoded by the ERG11 gene, are used to treat a variety of infections caused by Candida albicans. Azoles are known to induce expression of ERG11 mRNA. The ERG11 promoter was cloned 5' of the luciferase-coding region, and the induction of ERG11 expression by azoles was monitored by luciferase assays. Maximal induction of the ERG11 promoter by azoles occurs not during logarithmic growth but after the diauxic shift and requires azoles to be present throughout logarithmic growth. The effects of pH, carbon source, and aerobic or anaerobic growth on induction of the ERG11 promoter by azoles were analyzed. Treatment with terbinafine and fenpropimorph, which target other enzymes in the ergosterol biosynthetic pathway, also resulted in a delayed induction of ERG11 promoter activity. Nascent sterol synthesis was shown to parallel ERG11 promoter activity, and total sterols were reduced coincident with the timing of ERG11 promoter activation. These results as a whole suggest that expression of the ERG11 promoter is regulated in response to sterol depletion.