Genome Sequence of Streptococcus agalactiae Strain 09mas018883, Isolated from a Swedish Cow.

We announce the complete genome sequence of Streptococcus agalactiae strain 09mas018883, isolated from the milk of a cow with clinical mastitis. The availability of this genome may allow identification of candidate genes, leading to discovery of antigens that might form the basis for development of a vaccine as an alternative means of mastitis control.

Intragenomic rearrangement in TT viruses: a possible role in the pathogenesis of disease.

A role for the ubiquitous Torque teno (TT) viruses in the pathogenesis of disease has not been resolved. In vivo and in vitro intragenomic rearrangement of TT virus genomes has been demonstrated. Replication in cell culture of a subviral molecule (411 bp) occurs through oligomerisation of RNA transcripts. Although the functions of the respective TT viral genes, as well as the newly formed genes in the rearranged subviral molecules, are largely unknown, certain similarities to genes of plant viruses of the family Geminiviridae will be described. A degree of similarity to certain cellular genes poses the question as to a role of molecular mimicry in the pathogenesis of autoimmune disease and diabetes.

TT viruses: oncogenic or tumor-suppressive properties?

Torque teno (TT) viruses have been more frequently reported in malignant biopsies when compared to normal control tissue. The possible contribution of TT virus infection to human carcinogenesis or the potential oncolytic functions of these virus infections are being discussed based on available experimental evidence. The data could suggest an involvement of TT virus infections as an indirect carcinogen by modulating T cell immune responses. Significant oncolytic functions, potentially mediated by the inhibition of nuclear factor (NF)-kappaB transcription factor or by apoptin-like gene activities, are emerging to be less likely.

[Coincidental squamous cell cancers of the esophagus, head, and neck: risk and screening]. / "Field cancerization" im oberen Aerodigestivtrakt: Uberwachungsempfehlungen für Risikopersonen.

The term "field cancerization" was coined by Slaughter in1953 when describing multifocal synchronous and metachronous carcinogenesis in the upper aerodigestive system. Patients suffering from head and neck cancer (HNC) have or develop a second esophageal squamous cell cancer (ESCC) or bronchial cancer (BC) in 5-14% of cases. When a second esophageal cancer occurs in a patient with HNC, the prognosis is generally determined by the ESCC, and, unfortunately, it is poor. Screening and surveillance by Lugol chromoesophagoscopy enable early detection and curative treatment of second esophageal neoplasias. Surveillance appears to result in a survival benefit for HNC patients. Vice versa, patients with ESCC or BC have a risk of about 10% for developing HNC. Periodic pharyngolaryngoscopy is recommended for curatively treated ESCC or BC patients. Patients with field cancerization should be surveilled by a multidisciplinary approach.

[Coincidental squamous cell cancers of the esophagus and head and neck: risk and surveillance]. / Koinzidenz von Plattenepithelkarzinomen der Speiseröhre und Kopf-Hals-Karzinomen: Risiko und Früherkennung.

Patients suffering from head and neck cancer (HNC) have or will develop a second esophageal squamous cell cancer (ESCC) in 5 - 14 %. When a second esophageal neoplasm occurs in a HNC patient, the prognosis is generally determined by the ESCC, and unfortunately it is poor. Prospective clinical studies in Japan, Brazil, Taiwan, France and Germany have shown that screening or surveillance using Lugol chromoesophagoscopy enables early detection of second esophageal neoplasias. Such a surveillance results in a survival benefit for HNC patients. Vice versa, ESCC patients also have a risk of 9.3 - 11.4 % for a head and neck cancer. Periodic otolaryngeal examination and pharyngoscopy is recommended for curatively treated ESCC patients. Patients with a so-called field cancerisation of the airways and upper digestive tract thus require an interdisciplinary management and monitoring.

TAp63alpha indirectly regulates a cutaneous HPV promoter through complex formation with Jun family members.

The p63alpha isoforms of the p53 family have been demonstrated to play a crucial role in the development and differentiation of the skin. We show that expression of the TAp63alpha isoform leads to an upregulation of the cutaneous papillomavirus HPV 20 promoter, which is increased at least three-fold when c-Jun is co-expressed, in contrast to a minimal increase in activity in the presence of c-Jun alone. Co-expression of TAp63alpha with JunB or JunD, respectively, and in combination, leads to a reduction in the viral promoter activation measured by the expression of TAp63alpha alone. JunB and JunD also inhibits the additive effect exerted on the TAp63alpha activation by c-Jun. Co-immunoprecipitation assays demonstrate a complex formation of c-Jun, JunB and JunD with TAp63alpha through the SAM domain mediating protein-protein interactions, which is characteristic for p63alpha. Co-expression of p53 mutant R248W not only downregulates the differential modulation of the viral promoter by TAp63alpha alone and in the presence of the Jun family members, but leads to a reduction in the protein levels of the overexpressed c-Jun, JunB, JunD, as well as TAp63alpha. This model system provides insight into yet unknown pathways through which TAp63alpha and Jun may cooperate in the pathogenesis of HPV associated cutaneous lesions.

Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome.

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.

Identification of candidate sialome components expressed in ixodid tick salivary glands using secretion signal complementation in mammalian cells.

Ixodid ticks manipulate mammalian host pathways by secreting molecules from salivary glands. Novel cDNAs containing functional secretion signals were isolated from ixodid tick salivary glands using a signal sequence trap. Only 15/61 Rhipicephalus appendiculatus and 1/7 Amblyomma variegatum cDNAs had significant identity (< 1e-15) to previously identified sequences. Polypeptides that may interact with host pathways included a kinase inhibitor. Two proteins encoded homologues of the yolk protein vitellogenin and seventeen contained glycine-rich motifs. Four proteins without sequence matches had conserved structural folds, identified using a Threading algorithm. Predicted secretion signals were between fifteen and fifty-seven amino acids long. Four homologous polymorphic proteins contained conserved (26/27 residues) signal peptides. Ten functional tick secretion signals could not be unambiguously identified using predictive algorithms.

Epidermodysplasia verruciformis associated with neurofibromatosis type 1: coincidental association or model for understanding the underlying mechanism of the disease?

We describe a 25-year-old man with epidermodysplasia verruciformis (EV) associated with neurofibromatosis type 1 (NF1). The lesions, persisting for more than 15 years, consisted of widespread planar warts on the backs of the hands and wrists, and reddish-brown macules on the trunk, neck and face. During the last 5 years, our patient developed several epithelial tumours, namely solar keratoses, plaques of Bowen's disease and squamous cell carcinomas (SCCs). He also presented with NF1 lesions with neurofibromas, café-au-lait macules, axillary freckling and Lisch nodules. He had left tibial bowing. Polymerase chain reaction analysis of the skin lesions demonstrated the presence of human papillomavirus (HPV) 15 in a flat wart, HPV 20 in a plaque of Bowen's disease, and HPV 15 and HPV 20 in an SCC lesion. Both EV and NF1 show an inherited predisposition to malignancy but the molecular mechanism underlying tumour development is not fully understood. The appearance of both diseases in our patient may be a coincidental association but may also contribute to the identification of loci for susceptibility to NF1 and EV on chromosome 17.

Opposite regulation of the HPV 20-URR and HPV 27-URR promoters by ultraviolet irradiation and cytokines.

Epidemiological evidence implicates ultraviolet radiation and genetic changes (e.g., p53 mutations) as important factors in the etiology of nonmelanoma skin cancer. Little is known about a possible role of cutaneous papillomaviruses in these tumors. We previously reported both positive and negative regulation of the promoter activity of a number of HPV types by UV irradiation. To determine the underlying mechanism, we examined the influence of pro-inflammatory cytokines and MAP-kinases induced by UV irradiation by transfecting the HPV 20-URR and the HPV 27-URR into the RKO, HaCaT and H1299 cell lines expressing wild-type or mutated p53 or lacking p53, respectively. IL-1alpha, IL-1beta, IL-6, IL-17, TNF-alpha, as well as interferon-alpha, -beta and -gamma activated the promoter in the HPV 20-URR but inhibited the HPV 27-URR promoter. The effect of IL-1alpha and UV light was abolished by the addition of IL-1 receptor antagonist. UV irradiation induced a prolonged activation of JNK in HaCaT and H1299 but not in RKO cells, and its dephosphorylation was enhanced in the presence of p53 and the HPV-URRs.

Genome size and genetic map of Cowdria ruminantium.

Cowdria ruminantium is the cause of a serious tick-borne disease of domestic ruminants, known as heartwater or cowdriosis. The organism belongs to the tribe Ehrlichieae:, which contains obligate intracellular pathogens, causing several important animal and human diseases. Although a few C. ruminantium genes have been cloned and sequenced, very little is known about the size, gross structure and organization of the genome. This paper presents a complete physical map and a preliminary genetic map for C. ruminantium. Chromosomal C. ruminantium DNA was examined by PFGE and Southern hybridization. PFGE analysis revealed that C. ruminantium has a circular chromosome approximately 1576 kb in size. A physical map was derived by combining the results of PFGE analysis of DNA fragments resulting from digestion of the whole genome with KSP:I, RSR:II and SMA:I and Southern hybridization analysis with a series of gene probes and isolated macrorestriction fragments. A genetic map for C. ruminantium with a mean resolution of 290 kb was established, the first for a member of the Ehrlichieae: A total of nine genes or cloned C. ruminantium DNA fragments were mapped to specific KSP:I, RSR:II and SMA:I fragments, including the major antigenic protein gene, map-1.

Macrorestriction fragment profiles reveal genetic variation of Cowdria ruminantium isolates.

Macrorestriction profile analysis by pulsed-field gel electrophoresis (PFGE) was used to distinguish between seven isolates of Cowdria ruminantium from geographically different areas. Characteristic profiles were generated for each isolate by using the restriction endonucleases KspI, SalI, and SmaI with chromosomal sizes ranging between 1,546 and 1,692 kb. Statistical analysis of the macrorestriction profiles indicated that all the isolates were distinct from each other; these data contribute to a better understanding of the epidemiology of this pathogen and may be exploited for the identification of genotype-specific DNA probes.

Human papillomavirus E7 proteins stimulate proliferation independently of their ability to associate with retinoblastoma protein.

Studies on human papillomavirus type 16 have demonstrated that the product of the early gene, E7, plays a key role in the immortalization and malignant transformation of the host cell. Several of the biological activities of HPV16 E7 are mediated by inactivation of the members of the pocket protein family, pRb, p107 and p130. In this study, we have characterized the in vitro properties of five E7 proteins from benign and malignant HPV types (10, 32, 48, 54, 77). We show that these E7 proteins associate with pRb and p107 with different efficiencies. All E7s increased the proliferative rate of immortalized rodent fibroblasts cultured in 10% calf serum containing medium. This property is completely independent of their ability to associate with the pocket proteins. Furthermore, all E7s, except HPV10 E7, stimulate G1/S progression and activated the cyclin E and cyclin A promoter in the absence of growth factors. This activity also does not correlate with the E7-efficiency of binding the pocket proteins. Together these data provide evidence that different E7s alter the regulation of the cell cycle by diverse mechanism(s). Finally, this comparative analysis of the different E7 proteins demonstrates that the oncogenicity of a HPV type is not determined by the ability of E7 to associate with the pocket proteins.

Clinical course and treatment of haemorrhagic cystitis associated with BK type of human polyomavirus in nine paediatric recipients of allogeneic bone marrow transplants.

UNLABELLED: Of a total of 117 bone marrow transplant (BMT) recipients in the period from August 1988 to November 1995, 9 (7.7%) developed haemorrhagic cystitis. This condition was characterized in all nine patients by late onset (day +24 to +50 post-BMT), long duration (1 to 7 weeks), and the excretion of BK virus in the urine, as confirmed by electron microscopy, DNA hybridization and PCR analysis. Adenovirus was not involved. The serological assessment of BK virus-specific IgM and IgG pre- and post-BMT is consistent with viral reactivation in all patients, although a primary infection cannot be absolutely excluded in a single patient. A significant correlation between the use of high-dose busulphan (16 mg/kg) in the preparative regimen and development of haemorrhagic cystitis (P = 0. 0003) was evident. The severe course of the disease in two patients resulted in bladder tamponade; bleeding could not be inhibited with coagulation and laser treatment. Deterioration was prevented by bladder irrigation via a suprapubic catheter. Remission occurred spontaneously in all patients. CONCLUSION: BK virus induced haemorrhagic cystitis in a paediatric bone marrow transplantation recipients is characterized by late onset, long duration, viral reactivation and correlates to high-dose busulphan. Severe bleeding could not be influenced by surgical intervention.

Detection of HPV-20, HPV-23, and HPV-DL332 in a solitary eyelid syringoma.

PURPOSE: To report evidence of many human papillomavirus types occurring in a solitary syringoma clinically appearing as a papilloma. METHODS: A 57-year-old man presented with a 10-year history of an upper eyelid tumor. Histopathology, human papillomavirus-nested polymerase chain reaction, human papillomavirus-DNA cloning into vector pCR2.1, sequencing, and computer-assisted evaluation were performed. RESULTS: Histopathology demonstrated a solitary benign syringoma. HPV-20 and HPV-23 were present in one clone each, and HPV-5-related HPV-DL332 was present in 9 clones. CONCLUSION: Many human papillomavirus types may be detected in an ocular syringoma.