HPV16 genetic variation and the development of cervical cancer worldwide.

BACKGROUND: Factors that favour a small proportion of HPV16 infections to progress to cancer are still poorly understood, but several studies have implicated a role of HPV16 genetic variation. METHODS: To evaluate the association between HPV16 genetic variants and cervical cancer risk, we designed a multicentre case-control study based on HPV16-positive cervical samples (1121 cervical cancer cases and 400 controls) from the International Agency for Research on Cancer biobank. By sequencing the E6 gene, HPV16 isolates were classified into variant lineages and the European (EUR)-lineage isolates were subclassified by the common polymorphism T350G. RESULTS: Incidence of variant lineages differed between cases and controls in Europe/Central Asia (P=0.006, driven by an underrepresentation of African lineages in cases), and South/Central America (P=0.056, driven by an overrepresentation of Asian American/North American lineages in cases). EUR-350G isolates were significantly underrepresented in cervical cancer in East Asia (odds ratio (OR)=0.02 vs EUR-350T; 95% confidence interval (CI)=0.00-0.37) and Europe/Central Asia (OR=0.42; 95% CI=0.27-0.64), whereas the opposite was true in South/Central America (OR=4.69; 95% CI=2.07-10.66). CONCLUSION: We observed that the distribution of HPV16 variants worldwide, and their relative risks for cervical cancer appear to be population-dependent.

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

Urinary human polyomavirus and papillomavirus infection and bladder cancer risk.

BACKGROUND: The association of transitional cell carcinomas of the bladder (TCB) with Schistosoma haematobium suggested a possible role of infections in the aetiology of TCB. METHODS: In all, 114 TCB cases and 140 hospital controls from Pordenone Province were enrolled within an Italian multi-centric case-control study. Urine samples were screened for DNA from five human polyomaviruses (HPyV) (JCV, BKV, MCV, WUV, and KIV); SV40; and 22 mucosal human papillomaviruses (HPV) using highly sensitive PCR assays. Odds ratios (ORs) and corresponding confidence intervals (CIs) were computed for risk of TCB by HPyV- or HPV-positivity using unconditional logistic regression. RESULTS: Human polyomavirus prevalence was similar in TCB cases (71.7%) and controls (77.7%) (OR for TCB=0.85; 95% CI: 0.45-1.61). JCV was the most frequently detected HPyV type. No individual HPyV showed a significant association. Among cases, HPyV-positivity was not associated with tumour characteristics, but it was significantly lower in women than men and among current and former smokers than never smokers. Human papillomavirus was detected in seven cases and five controls (OR=1.52; 95% CI: 0.42-5.45). CONCLUSION: The present small study does not support an involvement of HPyV or HPV infection in TCB aetiology in immunocompetent individuals. Differences in HPyV-positivity by sex and smoking may derive from differences in either acquisition or persistence of the infection.

HPV infection in women with and without cervical cancer in Conakry, Guinea.

BACKGROUND: Cervical cancer incidence in western Africa is among the highest in the world. METHODS: To investigate human papillomavirus (HPV) infection in Guinea, we obtained cervical specimens from 831 women aged 18-64 years from the general population of the capital Conakry and from 77 locally diagnosed invasive cervical cancers (ICC). Human papillomavirus was detected using a GP5+/6+ PCR-based assay. RESULTS: Among the general population, the prevalence of cervical abnormalities was 2.6% by visual inspection and 9.5% by liquid-based cytology. Fourteen of 15 high-grade squamous intraepithelial lesions were visual inspection-negative. Human papillomavirus prevalence was 50.8% (32.1% for high-risk types) and relatively constant across all age groups. Being single or reporting > or =3 sexual partners was significantly associated with HPV positivity. HPV16 was the most common type, both among the general population (7.3%) and, notably in ICC (48.6%). HPV45 (18.6%) and HPV18 (14.3%), the next most common types in ICC, were also more common in ICC than in HPV-positive women with normal cytology from the general population. CONCLUSION: The heavy burden of HPV infection and severe cervical lesions in Guinean women calls for new effective interventions. Sixty-three per cent of cervical cancers are theoretically preventable by HPV16/18 vaccines in Guinea; perhaps more if some cross-protection exists with HPV45.

Synthesis and Biological Activity of Several Modified 5α-Androstanolone Derivatives.

Several new N-containing epiandrosterone derivatives modified by phenylacetic acid chloride were synthesized for biological activity studies. Compounds with antiviral activity were discovered among them and 3ß-hydroxy-1'-aryl-3'-methyl-5'-androstano[17,16-d]pyrazolines prepared by us earlier.

[The thoracic surgeon and the management of the bronchial biliary fistula of hydatid origin]. / Le chirurgien thoracique face à la fistule biliobronchique d'origine hydatique.

INTRODUCTION: The bronchial biliary fistula surgery is a major one, always going with a higher rate of complication especially in case of bile duct obstruction. The aim of this study is to find out the contribution of endoscopic sphincterotomy while reporting the results of surgical treatment of bronchial biliary fistulae by exclusive thoracotomy. METHODS: This was a retrospective study, which took place in the Department of Thoracic Surgery, University Hospital Hassan II, from January 2009 to March 2016. The parameters studied in connection with the bronchial biliary fistula of hydatid origin were: age, sex, origin, history of surgery especially for hepatic hydatid cyst, term of bilyptysie, imaging results, preoperative cholangiography indications, surgical treatment modalities and patients trends. RESULTS: A sample of 12 patients was included (6 men and 6 women) with an average age of 44 years old, with a gap spanning between 17 and 81 years. Seven patients had at least a history of hepatic hydatid surgery. The biliptysie was the main symptom in 8 patients. A biological cholestasis syndrome was found in 6 patients. The thoracoabdominal CT scan performed on all patients comes out with results in 100% of cases. Four patients received endoscopic retrograde cholangiography that allowed them to release the bile duct completely by sphincterotomy with extraction of hydatid membrane in one patient and with development of a biliary stent in another patient. The incision was a low posterolateral thoracotomy in 10 patients that went under surgery. It has allowed to deal in one-time liver and lung injuries combined with diaphragmatic breach repair. Inside the group of patients that went under surgery, the postoperative results were simple in 8 cases. We have noted an overall mortality rate of 18.2%. CONCLUSION: Bronchial biliary fistula surgery complications remains considerable despite the progress of diagnostic imaging. Preoperative endoscopic sphincterotomy is a milestone in the handling of this surgery. It may even be suggested as exclusive therapy in inoperable patients with significant biliptisy.

Activation of oncogenicity of the c-rel proto-oncogene.

Reticuloendotheliosis virus strain T (Rev-T) induces a lethal lymphoma in young birds and transforms avian lymphoid cells in vitro. The transforming gene of Rev-T, v-rel, was derived from the turkey proto-oncogene c-rel. Comparison of the nucleotide sequences of v-rel and c-rel indicates that in addition to several internal amino acid changes relative to c-rel, p59v-rel has amino acid sequences at both ends derived from the reticuloendotheliosis virus strain A-related virus env gene (K. C. Wilhelmsen, K. Eggleton, and H. M. Temin, J. Virol. 52:172-182, 1984). In this report, the v-rel sequences important for transformation were defined by constructing recombinant retroviruses in which c-rel sequences replaced the analogous v-rel sequences. These recombinant viruses expressing chimeric proteins were tested for their ability to transform spleen cells in vitro and to induce tumors in young chickens. Activation of the oncogenicity of c-rel in Rev-T required alteration of the amino terminus and the central region of the protein. Deletion of the noncoding sequences 3' to c-rel and of most of the helper virus-related env sequences was necessary for the formation of Rev-T.

Alternative excision products originating from a single integration of polyomavirus DNA.

The Cyp cell line consists of mouse cells transformed by a thermosensitive polyomavirus (Py) genome and routinely propagated at 39 degrees C. Cyp cells are readily induced to synthesize free Py DNA by being transferred to 33 degrees C. In one subclone (C12/a1/S48, or S48) of this line, such induction resulted in the intracellular accumulation of three discrete species of cyclic DNA, i.e., genomic Py DNA, RmI, and RmII. RmI and RmII are Py-mouse chimeras, each of which contains a distinct set of sequences originating from the site of integration. Conceivably, genomic Py DNA, RmI, and RmII could persist at 39 degrees C as free replicating plasmids or originate from distinct populations of cells in S48 cultures. The data indicated that all three species arise at 33 degrees C from a genetically homogeneous cell population in which neither RmI nor RmII replicates at 39 degrees C. Examination of the sequence at the viral-cellular junction unique to RmII indicated that this chimera is excised from the host chromosome through a recombination event involving a complex viral sequence and a simple cellular sequence. Therefore, RmII provides another example of precise recombination occurring between nonhomologous sequences in a mammalian cell, as already observed for RmI (B. S. Sylla, D. Huberdeau, D. Bourgaux-Ramoisy, and P. Bourgaux, Cell 37:661-667, 1984).

Synthesis and Antiviral Activity of Several N-Containing 5α-STEROIDS.

A study of the antiviral activity of several new hydrazones and amines and amides of 5α-steroids that were synthesized by us earlier found highly and moderately active compounds. The structures of the synthesized compounds were proven using IR, PMR, 13C NMR, and mass spectral data.

Simple acoustic multiplexer.

Simple structures enabling the multiplexing of acoustic waves are presented. Such structures are constructed out of two monomode acoustic wires and two masses bound together, and to the wires by springs. We show analytically that these simple structures can transfer with selectivity and in one direction one acoustic wavelength from one wire to the other, leaving neighbor acoustic wavelengths unaffected. We give closed-form relations enabling to obtain the values of the relevant physical parameters for this multiplexing phenomena to happen at a chosen wavelength. Finally, we illustrate this general theory by an application.

Prise en charge de la malnutrition aigüe chez l'enfant dans un hôpital secondaire sahelien

La malnutrition chez les enfants de moins de cinq ans est un problème majeur de santé publique dans les pays à faibles revenus, et contribue de manière significative à la mortalité dans cette tranche d'âge.Le but de ce travail était d'évaluer le profil épidémioclinique et thérapeutique des enfants malnutris pris en charge au centre de santé de référence de Nara.Méthode:IL s'est agi d'une étude rétrospective et descriptive,allant du 01/01/2016 au 31/12/2016.Tous les enfants d'âge compris entre 6 mois et 59 mois, admis pour malnutrition aigüe ont été inclus.Résultats:La malnutrition a été diagnostiquée chez quatre cent soixante un enfant, soit 15% des consultations et 50% des hospitalisations.L'âge médian était de 26 mois (2 mois 93 mois). Le sex ratio était 0,92 (M=222;F=239).Dixneuf pour cent des patients ont eu un sevrage progressif (n=90), et il a été brutal chez 371patients, soit 80%. La répartition des patients selon le Z score était le suivant: Z-score <-1 (n=15;3%), Z-score <-2 (n=46; 10%), Z-score <-3 (n=400; 87%). Le périmètre brachial moyen était de 105mm (99mm-124mm). A l'admission, l'hypoglycémie a été notée chez 45% (n=204). Les cas de marasme représentaient 80% (n=367) kwashiorkor 10% (n=48). La forme mixte de la malnutrition a représentée10% (n=46). Les pathologies associées à la malnutrition étaient: les pneumopathies (n=219; 47%), lepaludisme (n=115;25%) et les gastroentérites (n=68; 15%).Le F75 a été administré majoritairement pendant 3 mois dans 93% des cas. Pour la phase 2 du traitement, le Plumpy Nut et le F100 ont été respectivement administré à 88% et 12%.Le taux de récupération nutritionnelleétait de 95% (n=435).Cinq pour cent des patients sont décédés (n=26). La pneumonie a été la cause du décès dans 85% des cas. Le taux de guérison pour les cas de marasme et de kwashiorkor était respectivement de 94% et 93%.Conclusion:la malnutrition aigüe demeure fréquente et préoccupante en milieu pédiatrique sahelien. Une meilleure connaissance des mères sur le sevrage et la diversification alimentaire permettront d'améliorer l'état nutritionnel des enfants

Physical mapping of Xq24-25 around loci closely linked to the X-linked lymphoproliferative syndrome locus: an overlapping YAC map and linkage between DXS12, DXS42, and DXS37.

We have localized several markers in the Xq24-25 region containing DXS12, DXS42 and DXS37 which are closely linked to the X-linked lymphoproliferative syndrome (XLP) locus. A 850-kb restriction map has been established by mapping overlapping YACs and showed that DXS12 and DXS42 are physically linked within about 50 kb. DXS37 is separated from these two loci at a maximum distance of 3,700 kb. Several new probes have been generated which will contribute to further physical mapping of this region.

Physical map and cosmid contig encompassing a new interstitial deletion of the X-linked lymphoproliferative syndrome region.

The X-linked lymphoproliferative syndrome (XLP) is an inherited immuno-deficiency to Epstein-Barr virus infection that has been mapped to chromosome Xq25. Molecular analysis of XLP patients from ten different families identified a small interstitial constitutional deletion in 1 patient (XLP-D). This deletion, initially defined by a single marker, DF83, known to map to interval Xq24-q26.1, is nested within a previously reported and much larger deletion in another XLP patient (XLP-739). A cosmid minilibrary was constructed from a single mega-YAC and used to establish a contig encompassing the whole XLP-D deletion and a portion of the XLP-739 deletion. Based on this contig, the size of the XLP-D deletion can be estimated at 130 kb. The identification of this minimal deletion, within which at least a portion of the XLP gene is likely to reside, should greatly facilitate efforts in isolating the gene.

A new candidate region for the positional cloning of the XLP gene.

X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterised by selective susceptibility to Epstein-Barr virus and frequent association with malignant lymphomas chiefly located in the ileocecal region, liver, kidney and CNS. Taking advantage of a large bacterial clone contig, we obtained a genomic sequence of 197620 bp encompassing a deletion (XLP-D) of 116 kb in an XLP family, whose breakpoints were identified. The study of potential exons from this region in 40 unrelated XLP patients did not reveal any mutation. To define the critical region for XLP and investigate the role of the XLP-D deletion, detailed haplotypes in a region of approximately 20 cM were reconstructed in a total of 87 individuals from 7 families with recurrence of XLP. Two recombination events in a North American family and a new microdeletion (XLP-G) in an Italian family indicate that the XLP gene maps in the interval between DXS1001 and DXS8057, approximately 800 kb centromeric to the previously reported familial microdeletion XLP-D.

A mouse DNA sequence that mediates integration and excision of polyoma virus DNA.

In mouse cells transformed by a temperature-sensitive polyoma virus (Py) genome, the integrated viral genome recombines with adjacent chromosomal DNA to yield a small cyclic molecule (RmI) with defined viral and cellular components. We have cloned the cellular component (Ins), determined its sequence, and examined its distribution in normal mouse DNA. The sequence of Ins displays several homologies with that surrounding the replication origin (ori) of Py or SV40 DNA.

The temperature-sensitive defect in polyoma virus P155 mutant.

P155 is a temperature-sensitive mutant of polyoma virus that transforms normally, but replicates poorly, under restrictive conditions (Eckhart, 1969, 1975). We have observed that the temperature-sensitive character of P155 maps within the portion of the viral DNA coding exclusively for large T antigen, a viral gene product which is thermolabile in P155-infected cells. The phenotype of P155 may indicate that large T antigen fulfills different functions in virus replications and in cell transformation.

[Unusual radiologic aspect of a hydatid cyst]. / Aspect radiologique inhabituel d'un kyste hydatique.

The authors report us about an unusual hydatid cyst of the liver. Ultrasound, CT and MRI exams were used, and showed an unusual fatty component inside the lesion. The development of the disease in steatosic liver is not enough to explain the unusual density.

[Tumor-like focal nodular hyperplasia. Apropos of 3 cases observed at the Dakar Central Hospital from 1986 to 1989]. / Hyperplasie nodulaire focale à forme tumorale. A propos de 3 cas observés à l'Hôpital Principal de Dakar de 1986 à 1989.

Authors report three observations of Focal Nodular Hyperplasia, Tumor-like on two: senegalese female patients, 16 years and 37 years old, and a young senegalese man, 24 Years old. The mean age is about 25.5 years and oestro progestative intake has bean noted once. Diagnosis of Focal Nodular Hyperplasia was difficult and has been done twice after surgical intervention for chronic cholecystitis and blood peritonitis. The only complication reported, has been a rupture of nodular, causing the death of a patient. This benign tumor that never degenerates, does not need any particular treatment unless a stopping of oral contraception.