Selective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats.

The natural reservoir of Ebola virus (EBOV), agent of a zoonosis burdening several African countries, remains unidentified, albeit evidence points towards bats. In contrast, the ecology of the related Marburg virus is much better understood; with experimental infections of bats being instrumental for understanding reservoir-pathogen interactions. Experiments have focused on elucidating reservoir competence, infection kinetics and specifically horizontal transmission, although, vertical transmission plays a key role in many viral enzootic cycles. Herein, we investigate the permissiveness of Angolan free-tailed bats (AFBs), known to harbour Bombali virus, to other filoviruses: Ebola, Marburg, Taï Forest and Reston viruses. We demonstrate that only the bats inoculated with EBOV show high and disseminated viral replication and infectious virus shedding, without clinical disease, while the other filoviruses fail to establish productive infections. Notably, we evidence placental-specific tissue tropism and a unique ability of EBOV to traverse the placenta, infect and persist in foetal tissues of AFBs, which results in distinct genetic signatures of adaptive evolution. These findings not only demonstrate plausible routes of horizontal and vertical transmission in these bats, which are expectant of reservoir hosts, but may also reveal an ancillary transmission mechanism, potentially required for the maintenance of EBOV in small reservoir populations.

Tools for opening new chapters in the book of Treponema pallidum evolutionary history.

Treponema pallidum infections causing yaws disease and venereal syphilis are globally widespread in human populations, infecting hundreds of thousands and millions annually respectively; endemic syphilis is much less common, and pinta has not been observed in decades. We discuss controversy surrounding the origin, evolution and history of these pathogens in light of available molecular and anthropological evidence. These bacteria (or close relatives) seem to affect many wild African nonhuman primate (NHP) species, though to date only a single NHP Treponema pallidum genome has been published, hindering detection of spillover events and our understanding of potential wildlife reservoirs. Similarly, only ten genomes of Treponema pallidum infecting humans have been published, impeding a full understanding of their diversity and evolutionary history. Research efforts have been hampered by the difficulty of culturing and propagating Treponema pallidum. Here we highlight avenues of research recently opened by the coupling of hybridization capture and next-generation sequencing. We present data generated with such an approach suggesting that asymptomatic bones from NHP occasionally contain enough treponemal DNA to recover large fractions of their genomes. We expect that these methods, which naturally can be applied to modern biopsy samples and ancient human bones, will soon considerably improve our understanding of these enigmatic pathogens and lay rest to old yet unresolved controversies.

Plastic bronchitis requiring bronchoscopy.

OBJECTIVE: We report two cases of plastic bronchitis presenting with acute respiratory failure and mimicking foreign body inhalation. METHOD: The clinical findings, differential diagnoses and radiological investigation are discussed. RESULTS: Plastic bronchitis is an uncommon condition, particularly in children. The condition may present to otolaryngologists with symptoms mimicking foreign body inhalation. It is important to consider plastic bronchitis as a differential diagnosis, based on its clinical and radiological signs. Early intervention, in the form of bronchoscopy, can be both diagnostic and therapeutic. CONCLUSION: Plastic bronchitis is uncommon and its clinical and radiological features are non-specific. The recommended management is early bronchoscopy to establish the diagnosis and enable therapeutic intervention.

Prognosis in cystic fibrosis treated with continuous flucloxacillin from the neonatal period.

All newborn infants in East Anglia are screened for cystic fibrosis by blood immunoreactive trypsin assay at 7 days. Thirty eight infants with cystic fibrosis were randomised to treatment with either continuous oral flucloxacillin 250 mg/day (group P, n = 18) or with episodic antimicrobials as clinically indicated (group E, n = 20). Their progress was monitored from diagnosis to 24 months by a nurse coordinator who visited all infants regularly, at home and in hospital, to collect anthropometric, dietary, clinical, and microbiological data. Mean (range) age of confirmation of diagnosis was 5.7 weeks (1-14 weeks). There was no significant difference in birth weight, genotype, immunoreactive trypsin concentration, neonatal history, symptoms at diagnosis, pancreatic enzyme supplementation, or parental smoking history between the groups. Infants in group E had more frequent cough and a greater number of Staphylococcus aureus isolates than infants in group P. More infants of group E were admitted to hospital, had higher admission rates during the second year (19 v 5), for longer periods (6.4 v 2.2 days), despite receiving more than double the number of courses of antibiotics than group P infants (in addition to flucloxacillin). Continuous prophylactic flucloxacillin from early diagnosis of cystic fibrosis is associated with improved clinical progress during the first two years of life.

Disseminated growth of Hodgkin's-derived cell lines L540 and L540cy in immune-deficient SCID mice.

Local tumor growth has been reported after subcutaneous and intraperitoneal injection of Hodgkin's disease (HD) derived cell lines into different immunodeficient mouse strains. An animal model with disseminated growth of tumor cells would be useful for studying the in vivo biology of HD cells as well as for preclinical testing of new therapeutic regimens. For this purpose the HD-derived cell lines L540, L540cy, L428, and KM-H2 were injected intravenously into SCID mice. In contrast to L428 and KM-H2, widespread neoplasia occurred after a period of four to six weeks following injection of L540 and the subline L540cy. Lymph nodes were found to be the preferred site of tumor growth. CD30 surface antigen expression on Hodgkin cells and the karyotype of the tumor cells were preserved in the animal host. Thus, to a large extent, the SCID mouse model mimics the dissemination pattern of Hodgkin's disease in man. To evaluate the role of adhesion molecule expression in the dissemination of HD-derived cell lines, CD44 and members of the immunoglobulin, integrin, selectin, and Fc receptor families were quantified by flow cytometry. CD30 expression was also measured. Although CD44 expression has been correlated with dissemination in non-Hodgkin's lymphoma (NHL), this was not the case in the Hodgkin's SCID mouse model. CD44 was not expressed on the disseminating cell lines L540 and L540cy but was expressed in the nondisseminating lines L428 and KM-H2.

[Arteriovenous fistula of the kidney--angiography case descriptions]. / Arteriovenöse Kurzschlussverbindungen in der Niere--Angiographische Fallbeschreibungen.

Individual case reports serve to demonstrate the pathogenetically different renal arteriovenous shunt formations, such as congenital arteriovenous angioma, spontaneous arteriovenous aneurysm, iatrogenic arterio-venous fistula and neoplasia-conditioned arteriovenous fistula. These are discussed in detail, including treatment possibilities. The ranking of digital subtraction angiography is emphasised. Our case reports show that in preoperative diagnosis of pathological structures in the kidney, renovasography is an invaluable tool, especially with i.a. DSA technique, and is superior to all other methods such as sonography, CT, MR and colour-coded Doppler sonography. Due to improved techniques of angiography (markedly lower amounts of contrast medium when using catheters of narrow lumen) indication for i.a. DSA in haematuria of unknown origin should be liberal. Above all, the method should be performed at an early stage. If there is a NAD renal finding in the i.a. DSA renovasogram in renally conditioned haematuria even when using a 1024 x 1024 image matrix, it is advisable to perform selective renal arteriography to either exclude or confirm the existence of an intrarenal angioma, additionally in conventional sheet film technique because of the superior power of resolution.

[The "hepatoceliac collateral" in complete hepatomesenteric trunk--a first angiography observation]. / Die "hepato-zöliakle Kollaterale" beim kompletten Truncus hepato-mesentericus--Eine angiographische Erstbeobachtung.

In the example presented here we determined a complex anomaly of the large arterial vessels of the upper abdomen in combination with an intrahepatic vascular malformation (partially thrombosed haemangioma), this identification having become possible by superselective arteriography. There were two anastomoses of considerable calibre besides a complete truncus hepatomesentericus. We named one of these "hepato-coeliacal collateral". This collateral is now being described for the first time in literature and is demonstrated via angiography. Taking into account the embryogenesis of the visceral arteries and the organogenesis of the upper abdominal organs, we offer an interpretation of the development possibilities of the "hepato-coeliacal collateral".

MHC-controlled susceptibility to C3H-MTV-induced mouse mammary tumors is predominantly systemic rather than local.

The major histocompatibility complex (MHC) is one of the genetic factors involved in the control of susceptibility to MTV-induced mammary tumors in mice. Previously, genetic differences in mammary tumor susceptibility were shown to be mainly due to differences in susceptibility of the mammary gland itself. Such experiments, however, were carried out using inbred strains which differ in many genes. Therefore, the conclusion drawn from such experiments is not necessarily applicable to every gene involved. We tested whether in the strain C57BL/10 (B10, resistant) and the H-2 congeneic strain B10.A(5R) (5R, susceptible), which differ only at the MHC, the MHC-controlled difference in tumor susceptibility indeed resides in the mammary gland tissue itself, or is caused by systemic factors. Mammary glands of infant B10 and 5R mice were transplanted into mammary fat pads of C3H-MTV-infected mammectomized (B10 X 5R)F1 females. The hosts received a hypophyseal isograft under the kidney capsule or were subjected to force-breeding to provide hormonal stimulation necessary for mammary tumor development. Control groups of C3H-MTV-infected B10, 5R and (B10 X 5R)F1 females and (B10 X 5R)F1 females without C3H-MTV were also subjected to the 2 types of hormonal stimulation. There was no difference in susceptibility between the 5R and B10 mammary glands transplanted into C3H-MTV-infected F1 hybrid hosts. On the other hand, C3H-MTV-infected 5R and (B10 X 5R)F1 females were significantly more susceptible than the C3H-MTV-infected B10 females, when either of the 2 methods of hormonal stimulation was used. This indicates that, in the strains used, MHC-controlled susceptibility to C3H-MTV-induced mammary tumorigenesis is predominantly or exclusively controlled by systemic factors rather than by factors residing in the target tissue.

Low dose intraarterial cis-platinum/radiotherapy after local tumour preradiation.

The simultaneous use of intraarterial Cis-Platinum and Radiotherapy (CP/RT) was found to be a very effective and relatively little burdened treatment for a palliative treatment concept. This affects life quality as well as the remission--and survival times. The fast and continual remission with low CP/RT concentrations, even in extreme palliative cases, is surprising. CP/RT treatment shows additive and synergistic effects which are not explainable by the single effects of the cis-platinum dose used (60 mg/1.73 m2 in our case) or the total irradiation dose (e.g., 5 Gy TD) or the fractionation (e.g., 5 X 1 Gy), especially since the doses of each which were used are by themselves without therapeutic relevance. Only the combination of the modalities with a low dose two-day preradiation program induced the described effects.

[Embolization of the splenic artery. Emergency therapy in varices hemorrhage and in hypersplenism]. / Embolisation der Milzarterie. Eine Notfalltherapie bei Varizenblutung und beim Hypersplenismus.

In bleeding of oesophageal varices with resistance to common treatment embolisation of the splenic artery causes depression of the portal hypertension by forty per cent. Thrombosis of the splenic or portal vein as in splenectomies are not to be expected. The splenic vein remains open for later spleno-renal anastomosis. By occlusion of the splenic artery we were successful in stopping oesophageal bleeding. In a patient with dominant hypersplenism in portal hypertension the severity of the syndrome decreased after embolisation of the splenic artery. Thrombocytes, leukocytes and gammaglobulin increased.

[Herniations and prolapses of the diaphragm (author's transl)]. / Zwerchfellhernien und - Prolapse.

Diseases and changes of the diaphragmal region should be investigated radiologically. Computed tomography will give additional information. Special attention should be paid to patients after traumatic injuries of breast and body. 95% of which are sliding gastro-esophageal herniations.

Studies on lung tumours. V. Susceptibility of mice to dimethylnitrosamine-induced tumour formation in relation to H-2 haplotype.

Male mice of the strain A/Sn, of its congeneic partner strain A.SW, C57BL/10ScSnA (abbreviated: B10), and of two congeneic strains on a B10 background (B10.A and B10.AKM) were investigated for their susceptibility to lung tumour induction by dimethylnitrosamine (DMN) administered either by intraperitoneal injection or in the drinking water. Strain B10 (haplotype H-2b) proved to be very resistant, whereas strains A/Sn (H-2a) and A.SW (H-2s) were highly susceptible. The introduction of the haplotypes H-2a and H-2m in the resistant strain B10 resulted in a significant increase in sensitivity towards DMN-induced lung tumour formation. Lung tumour incidences in male (B10.A x B10)F hybrids, receiving DMN in drinking water, were found to be intermediate between, and significantly different from, the incidences of identically-treated parent strains B10.A and B10. Males of back-cross (B10.A x B10) x B10 BC proved to be of low susceptibility to lung tumour formation by DMN, tumour incidence being very low and not significantly different from that observed in identically-treated B10 males. It is concluded that, at least in the model system of B10-derived congeneic strains, H-2 haplotype is one of the factors important in determining susceptibility towards DMN-induced lung tumours. Comparison of C3Hf (H-2k), C3H/Sn (H-2k) and the latter's congeneic strains C3H.B10 (H-2b) and C3H.NB (H-2p) of male mice showed that these strains were moderately susceptible to both lung tumour and hepatoma formation by DMN. Accordingly, the presence of an H-2 haplotype from a lung-tumour-resistant strain (H-2b, B10) on the background of a strain of intermediate susceptibility (C3H) does not decrease susceptibility to lung tumour formation. The results were considered in the light of the H-2 haplotype dependence of spontaneous lung tumours, and consequently attention has been paid to the histological types of the induced and spontaneous lung tumours.

H-2-dependent regulation of the high level of expression of ecotropic murine leukemia virus.

Adult B10.Y mice, which are congenic with C57BL/10ScSn ((B10) mice for the H-2 region, expressed a high titer of infectious ecotropic virus in the spleen. F1 hybrids between B10.Y and B10 mice were negative or had very low levels of virus expression. In (B10.Y x B10)F2 segregant mice, the high virus phenotype segregated with the H-2pa haplotype of B10.Y, whereas the virus-negative phenotype was associated with the H-2b haplotype of B10. Molecular hybridization experiments with a selected ecotropic AKR murine leukemia virus cyclic DNA probe indicated that both partner strains possessed ecotropic virus sequences and that the number of sequences present was the same in B10.Y mice as in B10 mice. This finding excluded the possibility that the H-2-related effect might be due to the presence of additional viral structural genes within or close to the H-2 region of B10.Y mice. The level of expression of this endogenous ecotropic virus was therefore affected by regulatory genes of the H-2 region.

[Radiological diagnosis of the ösophagus with special attention to the ösophagogastric transition of the gastro-ösophageal reflux, reflux ösophagitis, hiatal hernias and ösophageal stenoses (author's transl)]. / Zur Röntgendiagnostik des Osophagus mit besonderer Berücksichtigung des ösophago-gastrischen Uberganges, des gastro-ösophagealen Refluxes, der Refluxösophagitis, der Hiatushernien und der Osophagusstenosen.

The inferior high-pressure zone acts like a functional sphincter. This is formed in the absence of a muscle correlate, via a regional predominance of the sphincter tone caused by inhibition of activity of the longitudinal muscles through the membrane phreno-oesophagea in the region of the vestibulum gastro-oesophageale. Pressure variations in the vestibulum caused by respiration, are governed by a "rein mechanism". Swallowing produces a brief reflectory breakdown of the inferior high-pressure zone in the longitudinal muscles of the ösophagus via myogenic ventricular stimulus condution. Gastro-ösophageal reflux can be regularly identified by means of suitable x-ray examination technique. Since, however, it is not possible to arrive at a quantitative and qualitative assessment of the reflux via roentgenology, the aim of radiological examination in case of clinical suspicion of reflux is to determine a) the factors favouring reflux, ie hiatal hernia, gastric and duodenal ulcer, stenosis of the pylorus, etc, b) the sequelae of a pathological reflux, eg reflux stenosis, reflux ulcer, brachyösophagus etc, as well as c) to assess the self-cleaning function of the ösophagus. It is possible to definitely identify hiatal hernia by radiology with a well-aimed examination technique, through the intrathoracal displacement of parts of the stomach, of Schatzki's ring, and the superhiatal displacement of the entire vestibulum gastro-oesophageale. It is also regularly possible to identify by serial radiography an organic ösophagus stenosis, using large quantities of barium swallow, although pathogenetic interpretation of the x-ray film may be difficulat. Functional stenosis can be defined by pharmacoradiography and manometry. In clinically suspected reflux ösophagitis, endoscopy and histology will supply more conclusive findings in respect of mucosal assessment than x-ray examination.