Classification of papillomaviruses

One hundred eighteen papillomavirus (PV) types have been completely described, and a yet higher number of presumed new types have been detected by preliminary data such as subgenomic amplicons. The classification of this diverse group of viruses, which include important human pathogens, has been debated for three decades. This article describes the higher-order PV taxonomy following the general criteria established by the International Committee on the Taxonomy of Viruses (ICTV), reviews the literature of the lower order taxa, lists all known "PV types", and interprets their phylogenetic relationship. PVs are a taxonomic family of their own, Papillomaviridae, unrelated to the polyomaviruses. Higher-order phylogenetic assemblages of PV types, such as the "genital human PVs", are considered a genus, the latter group, for example, the genus "Alpha-Papillomavirus". Lower-order assemblages of PV types within each genus are treated as species because they are phylogenetically closely related, but while they have distinct genomic sequences, they have identical or very similar biological or pathological properties. The taxonomic status of PV types, subtypes, and variants remains unchanged and is based on the traditional criteria that the sequence of their L1 genes should be at least 10%, 2-10%, and maximally 2% dissimilar from one another.     

Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo

To analyze the biological role of factor XII (FXII, Hageman Factor) in vivo, we generated mice deficient for FXII using a gene targeting approach on two distinct genetic backgrounds, i.e. mixed C57Bl/6J X 129X1/SvJ and inbred 129X1/SvJ. Homozygous FXII knockout (FXII(-)/(-)) mice showed no FXII plasma activity and had a markedly prolonged activated partial thromboplastin time (aPTT). In contrast, coagulation factors XI, VIII, IX, X,VII, V, II and fibrinogen did not differ between FXII(-/-) mice and their wild-type littermates. Heterozygous matings segregated according to the Mendelian inheritance indicating that FXII deficiency does not increase fetal loss. Furthermore, matings of FXII(-/-) males and FXII(-/-) females resulted in normal litter sizes demonstrating that total FXII deficiency in FXII(-/-) females does not affect pregnancy outcome. Also, gross and histological anatomy of FXII(-/-) mice was indistinguishable from that of their wild-type littermates on both genetic backgrounds. Thus it appears that deficiency of murine FXII does not cause thrombophilia or impaired fibrinolysis in vivo. These results indicate that FXII deficiency does not affect hemostasis in vivo and we anticipate that the FXII(-/-) mice will be helpful to elucidate the biological role(s) of FXII in health and disease.     

Functional MRI of the lung using hyperpolarized 3-helium gas

Lung imaging has traditionally relied on x-ray methods, since proton MRI is limited to some extent by low proton density in the lung parenchyma and static field inhomogeneities in the chest. The relatively recent introduction of MRI of hyperpolarized noble gases has led to a rapidly evolving field of pulmonary MRI, revealing functional information of the lungs, which were hitherto unattainable. This review article briefly describes the physical background of the technology, and subsequently focuses on its clinical applications. Four different techniques that have been used in various human investigations are discussed: ventilation distribution, ventilation dynamics, and small airway evaluation using diffusion imaging and oxygen uptake assessment.     

Hybrid segmentation and virtual bronchoscopy based on CT images

RATIONALE AND OBJECTIVES: Introduction of combination of the segmentation tool SegoMeTex and the virtual endoscopy system VIVENDI to perform virtual endoscopic inspections of the human lung. This virtual bronchoscopy system enables visualization of the tracheobronchial tree down to seventh generation. Furthermore, the modified virtual system visualizes hidden structures such as segmented vascular system or tumors. MATERIALS AND METHODS: The segmentation is based on image data acquired by a multislice computed tomography scanner. SegoMeTex is used to segment the tracheobronchial tree by a hybrid system with minimal user action. Similarly, the complementary pulmonary arterial can be segmented, whereas additional structures such as tumors are marked manually. On this dataset, subsequently, data structures of the inner surface for virtual endoscopy are generated. Finally, the dataset can be explored by a virtual bronchoscopy procedure using the VIVENDI system. RESULTS: The segmentation method was successfully tested on 22 patients. The hybrid segmentation system identified bronchi up to the sixth generation with a sensitivity of more than 58%, and a positive predictive value of more than 90%. After the segmentation, the datasets are explored interactively (>30 fps on a standard personal computer platform in real-time rendering) using the virtual endoscopy software. The exploration exposed a high-quality reconstruction, even of small structures throughout the dataset. CONCLUSION: Virtual bronchoscopy in combining with a highly sensitive segmentation is a valuable tool for the localization and measurement of stenosis for resection planning.     

The Intrinsic Optical Signal Evoked by Chiasm Stimulation in the Rat Suprachiasmatic Nuclei Exhibits GABAergic Day-Night Variation

Infrared light transmittance imaging was used in rat hypothalamic slices to record an intrinsic optical signal (IOS) of the cell ensemble in the suprachiasmatic nuclei (SCN), the locus of the endogenous circadian clock. Upon optic chiasm stimulation, a transient IOS was observed in an area conforming to the known retinohypothalamic tract innervation in the ventral SCN. An increase in extracellular Mg²⁺ concentration to 10 mM reduced the IOS, suggesting that the elicited IOS is dependent on synaptic transmission. D-2-Amino-5-phosphonopentanoic acid and muscimol suppressed the elicited IOS, indicating that NMDA and GABA_A receptor-mediated mechanisms were involved in cell ensemble activity reflected in the IOS. The extracellularly recorded spiking of SCN neurons located outside the IOS area remained largely unaffected by the afferent stimulus. Neurons located within the IOS area responded with a depressed electrical discharge, manifesting an inverse relationship between single-unit discharge and the optical measure. The influence of the endogenous circadian rhythm on the elicited IOS was assessed by carrying out daytime-dependent concentration-response experiments. NMDA and non-NMDA receptor specific compounds did not exhibit significant day-night differences, whereas GABA-specific ligands showed a significant day-night variation in activity. The competitive GABA_A receptor antagonist bicuculline enhanced the IOS exclusively in the daytime SCN. 5α-Pregnane-3α, 21-diol-20-one (allotetrahydrodeoxy-corticosterone), a neuroactive steroid that potentiates GABAergic inhibition, suppressed the IOS in the night-time SCN more than in the daytime SCN. This suggests that in the rat the level of extracellular GABA is higher in the night-time SCN compared to the daytime SCN.     

Triplets and quadruplets in Switzerland: comparison with singletons,and evolution over the last decade

AIMS: Main objectives were 1) to determine the incidence of higher multiple births from 1995 to 1998 in Switzerland, and 2) to evaluate neonatal mortality and morbidity. Secondary objectives were 3) to compare the results with those of matched singletons, and 4) to compare the present data to the first Swiss study (1985-1988). METHODS: Retrospective analysis of maternal and neonatal data obtained from all Swiss hospitals. RESULTS: The incidence of triplet births was 1/3247 and that of quadruplet births 1/81,186. The median gestational age was 32 5/7 weeks for triplets, and 28 6/7 weeks for quadruplets. The median birth weight was 1665 g for triplets and 1076 g for quadruplets. Perinatal mortality was 6% for triplets and 19% for quadruplets. Respiratory distress syndrome was the major morbidity as diagnosed in 52% of triplets and 81% of quadruplets. A comparison of triplets with matched singletons showed no significant differences in morbidity and mortality. Compared with the first Swiss study, the mortality rate decreased, while the incidence of triplets increased but decreased for quadruplets. CONCLUSION: The incidence of higher-order multiple births in Switzerland dropped for quadruplets in the last decade but has increased for triplets. The mortality and morbidity of triplets is comparable to that of singletons with a similar gestational age.     

Natural course and burden of bipolar disorders

Despite an abundance of older and more recent retrospective and considerably fewer prospective-longitudinal studies in bipolar disorders I and II, there are still remarkable deficits with regard to our knowledge about the natural course and burden. The considerable general and diagnosis-specific challenges posed by the nature of bipolar disorders are specified, highlighting in particular problems in diagnostic and symptom assessment, shifts in diagnostic conventions and the broadening of the diagnostic concept by including bipolar spectrum disorders. As a consequence it still remains difficult to agree on several core features of bipolar disorders, such as when they begin, how many remit spontaneously and how many take a chronic course. On the basis of clinical and epidemiological findings this paper summarizes (i) a significant need to extend the study of the natural course of bipolar disorder in clinical samples beyond the snapshot of acute episodes to the study of the mid-term and long-term symptom course, associated comorbidities and the associated burden of the disease. (ii) In terms of epidemiological studies, that are also of key importance for resolving the critical issues of threshold definitions in the context of the bipolar spectrum concept, there is a clear need for identifying the most relevant risk factors for the first onset and those for the further illness progression in early stages. Since there are some indications that these critical processes might start as early as adolescence, such studies might concentrate on young cohorts and clearly before these prospective patients come to clinical attention. (iii) The value of both types of studies might be enhanced, if beyond the use of standardized diagnostic interview, special attempts are made to use prospective life- and episode-charting methods for bipolar illnesses.     

Relationship of serum adiponectin and leptin concentrations with body fat distribution in humans

OBJECTIVE: We investigated whether serum concentrations of adiponectin are determined by body fat distribution and compared the findings with leptin. RESEARCH METHODS AND PROCEDURES: Serum concentrations of adiponectin and leptin were measured by radioimmunoassay (n = 394) and analyzed for correlation with sex, age, and body fat distribution, i.e., waist-to-hip ratio, waist and hip circumference, and subcutaneous adipose tissue area of the lower leg as assessed by magnetic resonance imaging. RESULTS: After adjusting for sex and percentage of body fat, adiponectin was negatively (r = -0.17, p < 0.001) and leptin was positively (r = 0.22, p < 0.001) correlated with waist-to-hip ratio. Leptin, but not adiponectin, correlated with both waist (r = 0.49, p < 0.001) and hip circumference (r = 0.46, p < 0.001). Furthermore, leptin, but not adiponectin, correlated with the proportion of subcutaneous fat of the lower leg cross-sectional area (r = 0.37, p < 0.001). DISCUSSION: These data suggest that both adipocytokines are associated with central body fat distribution, and serum adiponectin concentrations are determined predominantly by the visceral fat compartment.     

Value of contrast-enhanced MR angiography and helical CT angiography in chronic thromboembolic pulmonary hypertension

The aim of this study was to evaluate the diagnostic value of contrast-enhanced MR angiography (ce MRA) and helical CT angiography (CTA) of the pulmonary arteries in the preoperative workup of patients with chronic thromboembolic pulmonary hypertension (CTEPH). The ce MRA and CTA studies of 32 patients were included in this retrospective evaluation. Image quality was scored by two independent blinded observers. Data sets were assessed for number of patent segmental, subsegmental arteries, and number of vascular segments with thrombotic wall thickening, intraluminal webs, and abnormal proximal to distal tapering. Image quality for MRA/CTA was scored excellent in 16 of 16, good in 11 of 14, moderate in 2 of 5, and poor in no examinations. The MRA/CTA showed 357 of 366 patent segmental and 627 of 834 patent subsegmental arteries. CTA was superior to MRA in visualization of thrombotic wall thickening (339 vs 164) and of intraluminal webs (257 vs 162). Abnormal proximal to distal tapering was better assessed by MRA than CTA (189 vs 16). In joint assessment of direct and indirect signs, MRA and CTA were equally effective (353 vs 355). MRA and CTA are equally effective in the detection of segmental occlusions of the pulmonary arteries in CTEPH. CTA is superior for the depiction of patent subsegmental arteries, of intraluminal webs, and for the direct demonstration of thrombotic wall thickening.