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PubMed2006

A segmental polynomial model of ventricular electrograms as a simple and efficient morphology discriminator for implantable devices.

BACKGROUND: The goal of this study is to construct a polynomial model of the ventricular electrogram (EGM) that faithfully reproduces the EGM and can be implemented in current, low computational power implantable devices. Such a model of ventricular EGMs is still lacking. METHODS: New Zealand White rabbits underwent chronic implantation of pacemakers through a left thoracotomy approach. Unipolar ventricular EGMs sampled at a frequency of 1 kHz were stored digitally in 1-minute segments before and after intravenous injection of isoproterenol or procainamide. Each cardiac cycle was divided into a QR and an RQ segment which were modeled separately using a 6th order polynomial equation. RESULTS: The 14 coefficients of each cardiac cycle were reproducible throughout the baseline recordings (r > or = 0.94, P < 0.002). Isoproterenol caused no changes in the coefficients of the QR segment but significantly altered all but one of the seven coefficients of the RQ segment (p(6)= 0.0039, p(5)= 0.017, p(4)= 0.00007, p(3)= 0.112, p(2)= 0.00016, p(1)= 0.0086, p(a)= 0.00003). Procainamide caused statistically significant changes in both QR segment (p(6)= 0.018, p(5)= 0.287, p(4)= 0.019, p(3)= 0.176, p(2)= 0.016, p(1)= 0.362, p(a)= 0.000044) and RQ segment (p(6)= 0.0028, p(5)= 0.036, p(4)= 0.002, p(3)= 0.058, p(2)= 0.022, p(1)= 0.718, p(a)= 0.0018) coefficients. CONCLUSION: Our data demonstrate the feasibility of a segmental polynomial equation that reproduces the phases of depolarization and repolarization of the rabbit EGM. This model is reproducible and demonstrates the expected changes with antiarrhythmic drug administration. If reproduced in humans, these findings can have wide applications in patients with implantable devices, ranging from morphologic discrimination of arrhythmias to early detection of metabolic derangements or drug effects.

Animals↗
PubMed2005

[Familial occurrence of a type 2 segmental manifestation of cutaneous leiomyomatosis].

BACKGROUND: There are several malignant or benign skin diseases which can be explained by the phenomenon of mosaicism or segmental manifestation, e. g. segmental neurofibromatosis 1 or cutaneous leiomyomatosis. Loss of heterozygosity is a crucial element for segmental manifestations. Two types of segmental manifestations can be defined in autosomal dominant skin diseases such as cutaneous leiomyomatosis. Type 1 is caused by a novel postzygotic segmental mutation; type 2 reflects an additional postzygotic loss of heterozygosity of the gene locus responsible for cutaneous leiomyomatosis in a initially heterozygous embryo. Loss of heterozygosity is a genetic process when a heterozygous cell becomes homozygous or hemizygous by loosing the corresponding wild-type allele. This phenomenon can be regarded as a precondition for tumor growth. In type-2 cases, the segmental manifestation is more distinctive with additional disseminated disease because of a germline mutation with heterozygosity of all somatic cells outside the strongly affected area. PATIENTS AND METHODS: A 74-year-old female patient and her 52-year-old son presented with segmental leiomyomas following the lines of Blaschko as well as disseminated skin tumors. The woman has undergone hysterectomy at the age of 29 because of multiple uterine leiomyomas, as had her mother and grandmother. RESULTS: Based on their typical clinical appearance, these cases represent the rare familial occurrence of type-2 manifestation of leiomyomas which indicates a postzygotic loss of the wild-type allele. CONCLUSION: Very unusual is the familial occurrence in mother and son of this type-2 manifestation of cutaneous leiomyomatosis. Apparently the gene locus is prone to a postzygotic loss of heterozygosity.

Aged↗
PubMed1975

Accumulation of calcium by retinal outer segments.

Two preparations of bovine photoreceptors, including intact and lysed outer segments, are used to study accumulation of Ca++ in order to differentiate between binding and transport. The two preparations accumulate initially roughly equal amounts of Ca++ in the presence or absence of ATP. In the absence of ATP no further accumulation occurs. With ATP accumulation continues most rapidly in intact outer segments. The additioesults in kinetics of uptake similar to those in the absence of ATP. Thus the initial phase of Ca++ accumulation is predominantly due to binding, while that induced by ATP is due to transport. Accumulation of Ca++ by outer segments can be stimulated by preloading them with ATP suggesting that ATP enters the structures and acts intracellularly. Illumination decreases binding of Ca++ to outer segments but does not consistently affect transport. After illumination more Ca++ is retained by intact than lysed outer segments indicating that plasma membrane acts as a barrier to the escape of Ca++. Phospholipids and protein appear to be responsible for Ca++ binding of outer segments as suggested by a reduced binding ability after removal of these constituents. Phosphatidyl ethanolamine is the main phospholipid class of outer segments.

Adenosine Triphosphate↗
PubMed1976

Physiological properties and receptive fields of mechanosensory neurones in the head ganglion of the leech: comparison with homologous cells in segmental ganglia.

A study of the head ganglion of the leech was made to compare the properties of specific sensory cells in this ganglion with those of homologous neurones in the segmental ganglia. 1. In the head ganglion, cells were identified that had electrical properties, sensory modalities and adaptation properties similar to those of touch (T), pressure (P) and nociceptive (N) cells in the segmental ganglia. The cell bodies of these neurones were situated in characteristics positions that could be correlated with those in the segmental ganglia. Several lines of evidence suggested that they were primary sensory neurones. Fewer T, P and N neurones were identified in the head ganglion than would be expected from its six constituent segmental ganglia. 2. The receptive fields of identified T, P and N cells were situated on the external surface of the head and the interior of the mouth with considerable overlap. They were generally smaller in size than those situated on the main part of the body. The receptive fields were also displaced anteriorly so that some of them were situated in segments anterior to those of the innervating cells. 3. The morphology of the sensory cells in the head ganglion was studied by intracellular injection of horseradish perioxidase. The general branching characteristics of the cells and the structural appearance of their processes resembled those of homologous cells in the segmental ganglia. However, the routes taken to the periphery by some of the cells were not constant from head ganglion to head ganglion. This variability was confirmed by electrophysiological evidence, and differed from the constancy seen in segmental sensory cells.

Action Potentials↗
PubMed1990

Characteristics of Na+ channels and Cl- conductance in resealed muscle fibre segments from patients with myotonic dystrophy.

1. Electrical and contractile properties of resealed fibre segments were investigated by a variety of in vitro techniques. The preparations were removed from skeletal muscles of normal subjects and of eight patients with myotonic dystrophy. 2. Several hours after removal, fibre segments from normal subjects and those patients in whom myotonia was the primary symptom had resting membrane potentials of approximately -80 mV. In contrast, fibre segments obtained from patients in whom muscle dystrophy was more expressed were depolarized (-60 to -70 mV). 3. Contractions induced in fibre segments of myotonic muscle which had normal potentials were characterized by slowed relaxation which was due to electrical after-activity. 4. After single stimuli, long-lasting (3-100) runs of action potentials were recorded intracellularly from the myotonic muscle. In some of these fibre segments complex repetitive discharges were observed: multiple sites of locally gated currents were identified. 5. The three-electrode voltage clamp was used to determine the total membrane conductance, gm, and the ion component conductances. All fibres of a particular patient had similar conductances. However, the Cl- conductance varied from patient to patient from normal (74% of gm) to low values (30% of gm). The K+ conductance was normal in all fibres of all patients. 6. The patch-clamp technique was used to record currents through single Na+ channels of the sarcolemma. After treatment of the fibre segments with collagenase gigaohm seals were routinely obtained. The rate of success was greater when using the cell-attached mode than the inside-out mode. 7. Sodium channel currents were elicited by depolarizing voltage steps which produced an initial burst of Na+ channel openings. Up to ten channels were activated simultaneously when the patch was depolarized to potentials more positive than -30 mV. The Na+ channels re-opened very rarely in controls. The macroscopic sodium current, INa, was reconstructed by averaging depolarizing pulses. The time constant of rapid decay of INa reflecting macroscopic inactivation, the onset of INa and the amplitude of INa were voltage dependent. The mean amplitude of the current produced by re-openings was on average only 0.11 +/- 0.04% of the amplitude of the peak current. 8. Late openings of the Na+ channels were frequent in patches on the myotonic fibre segments. The amplitude of the current produced by re-openings was as high as about 0.75 +/- 0.11% of the amplitude of the peak current.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1993

A relay for input from group II muscle afferents in sacral segments of the cat spinal cord.

1. A neuronal relay for input from group II afferents of hindlimb muscle nerves has been found in the previously little explored sacral segments of the cat spinal cord. 2. Electrical stimulation of group II muscle afferents of a number of nerves evoked negative potentials on the surface (cord dorsum potentials) and population postsynaptic potentials (field potentials) within the sacral segments. The largest potentials were evoked by stimulation of the posterior biceps-semitendinosus and triceps surae nerves which evoke much smaller potentials in other segments. Group II afferents of other nerves, notably those which have their main relay within the middle lumbar segments, were much less effective. 3. The sites at which cord dorsum and field potentials evoked by group II muscle afferents were recorded varied in relation to the external topography of the L7-S2 spinal segments but were consistent in their location relative to the pudendal motor nucleus (Onuf's nucleus). Potentials evoked by group II afferents of the posterior biceps and semitendinosus nerves peaked at a level corresponding to the rostral half of Onuf's nucleus and potentials evoked by afferents of the gastrocnemius nerves peaked just rostral to this nucleus. The largest field potentials (of 0.5-1.0 mV) were recorded within the dorsal horn. Field potentials in the intermediate zone were much smaller (< 0.3 mV) and were seen less frequently. 4. Evidence was obtained that the dorsal horn field potentials are to a great extent evoked monosynaptically by the fast conducting fraction of group II muscle afferents: (i) they were evoked at short latencies (2.4-2.7 ms from the stimulus; 1.3-1.7 ms from group I components of afferent volleys and 0.5-0.7 ms from group II components of these volleys), (ii) the conduction times of impulses in the fastest conducting fraction of group II afferents, between the sacral segments (where these impulses were induced by intraspinal stimuli) and the peripheral nerves, were only about 0.5 ms shorter than the latencies of field potentials recorded at the site of intraspinal stimulation and evoked by stimulation of the same peripheral nerves and, (iii) the field potentials followed repetitive stimuli without temporal facilitation. 5. Negative cord dorsum and field potentials were also evoked by small stretches of the semitendinosus and triceps surae muscles. Although they were smaller than potentials evoked by electrical stimulation of sensory fibres and appeared at longer latencies, their presence is consistent with a contribution of muscle spindle afferents to the actions of group II muscle afferents within the sacral segments.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed2002

Hypertonic fluids are secreted by medial and lateral segments in duck (Anas platyrhynchos) nasal salt glands.

Indwelling catheters were used to collect fluid directly from the medial and lateral segments of duck nasal salt glands showing, for the first time, that the secretions are fully hypertonic before reaching the medial and lateral drainage ducts. Using this method it was possible to show that (a) there is a functional symmetry between the left and right salt glands, (b) the medial segment always secretes fluid at approximately twice the rate of the lateral segment and (c) fluid secreted by the medial segment has the same ionic composition but variable ion concentrations when compared with fluid from the lateral segment. A 12 % increase in post-segmental fluid osmolality was probably due to the evaporation of water from epithelial surfaces in the nasal cavities during breathing. A post-segmental outflux of Ca(2+), Mg(2+) and Cl(-) in the medial and lateral collecting ducts and/or nasal epithelium may be of adaptive significance when birds inhabit calcium- and magnesium-rich marine environments.

Animals↗
PubMed2003

Prostate boundary segmentation from 3D ultrasound images.

Segmenting, or outlining the prostate boundary is an important task in the management of patients with prostate cancer. In this paper, an algorithm is described for semiautomatic segmentation of the prostate from 3D ultrasound images. The algorithm uses model-based initialization and mesh refinement using an efficient deformable model. Initialization requires the user to select only six points from which the outline of the prostate is estimated using shape information. The estimated outline is then automatically deformed to better fit the prostate boundary. An editing tool allows the user to edit the boundary in problematic regions and then deform the model again to improve the final results. The algorithm requires less than 1 min on a Pentium III 400 MHz PC. The accuracy of the algorithm was assessed by comparing the algorithm results, obtained from both local and global analysis, to the manual segmentations on six prostates. The local difference was mapped on the surface of the algorithm boundary to produce a visual representation. Global error analysis showed that the average difference between manual and algorithm boundaries was -0.20 +/- 0.28 mm, the average absolute difference was 1.19 +/- 0.14 mm, the average maximum difference was 7.01 +/- 1.04 mm, and the average volume difference was 7.16% +/- 3.45%. Variability in manual and algorithm segmentation was also assessed: Visual representations of local variability were generated by mapping variability on the segmentation mesh. The mean variability in manual segmentation was 0.98 mm and in algorithm segmentation was 0.63 mm and the differences of about 51.5% of the points comprising the average algorithm boundary are insignificant (P < or = 0.01) to the manual average boundary.

Algorithms↗
PubMed2004

Comparison between manual and automatic segment generation in step-and-shoot IMRT of prostate cancer.

PURPOSE: To compare two methods to generate treatment plans for intensity-modulated radiotherapy (IMRT) of prostate cancer, delivered in a step-and-shoot mode. The first method uses fluence optimization (inverse planning) followed by conversion of the fluence weight map into a limited number of segments. In the second method, segments are manually assigned using a class solution (forward planning), followed by computer optimization of the segment weights. METHODS: Treatment plans for IMRT, utilizing a simultaneous integrated boost, were created. Plans comprise a five-field technique to deliver 78 Gy to the prostate plus seminal vesicles. Five patients were evaluated. Optimization objectives of both planning approaches concerned dose coverage of the target volumes and the dose distribution in the rectal wall. The two methods were evaluated by comparing dose distributions, the complexity of the resulting plan and the time expenditure to generate and to deliver the plan. RESULTS: For both planning approaches 99% of the target volumes received 95% of the prescribed dose, which complies with our planning objectives. Inverse planning resulted in more conformal dose distributions than forward planning (conformity index: 1.37 versus 1.51). Inverse planning reduced the dose to the rectal wall compared to a manually designed plan, albeit to a small extent. The theoretical probability of severe rectal proctitis and/or stenosis was reduced on average by 1.9% with inverse planning. Maximal sparing of the rectal wall was achieved with inverse planning for a patient whose target volume was partly wrapped around the rectum. The number of segments generated with inverse planning ranged between 33 and 52, and between 9 and 13 segments for manually created segments. CONCLUSION: Dose coverage of the planning target volumes is adequate for both approaches of planning. Inverse planning results in slightly better dose distributions with respect to the rectal wall compared to manual planning, at the cost of an increase of the number of segments by a factor of 3.

Humans↗
PubMed2005

A method and software for segmentation of anatomic object ensembles by deformable m-reps.

Deformable shape models (DSMs) comprise a general approach that shows great promise for automatic image segmentation. Published studies by others and our own research results strongly suggest that segmentation of a normal or near-normal object from 3D medical images will be most successful when the DSM approach uses (1) knowledge of the geometry of not only the target anatomic object but also the ensemble of objects providing context for the target object and (2) knowledge of the image intensities to be expected relative to the geometry of the target and contextual objects. The segmentation will be most efficient when the deformation operates at multiple object-related scales and uses deformations that include not just local translations but the biologically important transformations of bending and twisting, i.e., local rotation, and local magnification. In computer vision an important class of DSM methods uses explicit geometric models in a Bayesian statistical framework to provide a priori information used in posterior optimization to match the DSM against a target image. In this approach a DSM of the object to be segmented is placed in the target image data and undergoes a series of rigid and nonrigid transformations that deform the model to closely match the target object. The deformation process is driven by optimizing an objective function that has terms for the geometric typicality and model-to-image match for each instance of the deformed model. The success of this approach depends strongly on the object representation, i.e., the structural details and parameter set for the DSM, which in turn determines the analytic form of the objective function. This paper describes a form of DSM called m-reps that has or allows these properties, and a method of segmentation consisting of large to small scale posterior optimization of m-reps. Segmentation by deformable m-reps, together with the appropriate data representations, visualizations, and user interface, has been implemented in software that accomplishes 3D segmentations in a few minutes. Software for building and training models has also been developed. The methods underlying this software and its abilities are the subject of this paper.

Algorithms↗
PubMed2000

Segmentation of suspicious clustered microcalcifications in mammograms.

We have developed a multistage computer-aided diagnosis (CAD) scheme for the automated segmentation of suspicious microcalcification clusters in digital mammograms. The scheme consisted of three main processing steps. First, the breast region was segmented and its high-frequency content was enhanced using unsharp masking. In the second step, individual microcalcifications were segmented using local histogram analysis on overlapping subimages. For this step, eight histogram features were extracted for each subimage and were used as input to a fuzzy rule-based classifier that identified subimages containing microcalcifications and assigned the appropriate thresholds to segment any microcalcifications within them. The final step clustered the segmented microcalcifications and extracted the following features for each cluster: the number of microcalcifications, the average distance between microcalcifications, and the average number of times pixels in the cluster were segmented in the second step. Fuzzy logic rules incorporating the cluster features were designed to remove nonsuspicious clusters, defined as those with typically benign characteristics. A database of 98 images, with 48 images containing one or more microcalcification clusters, provided training and testing sets to optimize the parameters and evaluate the CAD scheme, respectively. The results showed a true positive rate of 93.2% and an average of 0.73 false positive clusters per image. A comparison of our results with other reported segmentation results on the same database showed comparable sensitivity and at the same time an improved false positive rate. The performance of the CAD scheme is encouraging for its use as an automatic tool for efficient and accurate diagnosis of breast cancer.

Biophysical Phenomena↗
PubMed1998

Acceptability for temporal modification of single vowel segments in isolated words.

Few perceptual studies of the temporal aspects of speech have investigated the influence of changes in segmental durations in terms of acceptability. Aiming to contribute to the assessment of rules for assigning segmental durations in speech synthesis, the current study measured the perceptual acceptability of changes in the segmental duration of vowels as a function of the segment attributes or context, such as base duration, temporal position in a word, vowel quality, and voicing of the following segment. Seven listeners estimated the acceptability of word stimuli in which one of the vowels was subjected to a temporal modification from -50 ms (for shortening) to +50 ms (for lengthening) in 5-ms steps. The temporal modification was applied to vowel segments in 70 word contexts; their durations ranged from 35-145 ms, the mora position in the word was first or third, the vowel quality was /a/ or /i/, and the following segment was a voiced or an unvoiced consonant. The experimental results showed that the listeners' acceptable range of durational modification was narrower for vowels in the first moraic position in the word than for those in the third moraic position. The acceptable range was also narrower for the vowel /a/ than for the vowel /i/, and similarly narrower for vowels followed by unvoiced consonants than for those followed by voiced consonants. The vowel that fell into the least vulnerable class (the third /i/, followed by a voiced consonant) required 140% of the modification of that which fell into the most vulnerable class (the first /a/, followed by an unvoiced consonant) to yield the same acceptability decrement. In contrast, the effect of the original vowel duration on the acceptability of temporal modifications was not significant despite its wide variation (35-145 ms).

Humans↗
PubMed1976

Evidence for a complex life cycle and endospore formation in the attached, filamentous, segmented bacterium from murine ileum.

Light and electron microscope observations showed that the filamentous, segmented bacterium commonly found attached to the ileal epithelium of rats and mice undergoes a complex life cycle. Filaments comprising up to 90 segments were attached to the microvillous border of absorptive epithelial cells by a specialized terminal holdfast segment. Starting at the free end of the filament and progressing toward the attached end, undifferentiated segments were converted into reproductive or mother segments. Within each mother cell two new holdfast segments developed. As the holdfasts matured, their mother cells degenerated and released them into the intervillar space where they attached, grew, and divided to produce new segmented filaments. Alternately, in some filaments, newly formed but not yet released holdfasts were converted into endospores, which were released in the same manner as holdfasts, presumably to spread the bacterial colony to other members of the rodent population.

Animals↗
PubMed1994

Recognition specificity of the duplicated segments present in Clostridium thermocellum endoglucanase CelD and in the cellulosome-integrating protein CipA.

The binding specificity of the duplicated segments borne by Clostridium thermocellum endoglucanase CelD and by the cellulosome-integrating protein CipA was investigated. The fusion protein CelC-DSCelD, in which the duplicated segment of CelD was fused to the COOH terminus of endoglucanase CelC, bound with an affinity of 4.7 x 10(7) M-1 to the fusion protein MalE-RDCipA, in which the seventh receptor domain of CipA was grafted onto the COOH terminus of the Escherichia coli maltose-binding protein MalE. The affinity of CelC-DSCelD for the homologous chimeric protein MalE-RDORF3p, carrying the receptor of the surface protein ORF3p, was 6.9 x 10(6) M-1. The fusion protein CelC-DSCipA, in which the duplicated segment of CipA was grafted onto the COOH terminus of CelC, did not bind detectably to MalE-RDCipA or MalE-RDORF3p. However, Western blotting (immunoblotting) experiments indicated that the duplicated segment of CipA was able to bind to a set of C. thermocellum proteins which are different from those recognized by the duplicated segment of CelD. These results argue against the hypothesis that ORF3p interacts with the duplicated segment of CipA. More probably, ORF3p binds to individual cellulases and hemicellulases harboring duplicated segments.

ATP-Binding Cassette Transporters↗
PubMed1978

Segments of influenza virus complementary RNA synthesized in vitro.

In the presence of Mg(2+) and a specific primer, ApG or GpG, the influenza WSN virion transcriptase synthesizes large, polyadenylic acid-containing complementary RNA (cRNA) (Plotch and Krug, J. Virol., 21:24-34, 1977). After removal of its polyadenylic acid with RNase H in the presence of polydeoxythymidylic acid, the in vitro cRNA distributed into seven discrete bands during electrophoresis in acrylamide gels containing 6 M urea. The eight known segments of virion RNA (vRNA) also distributed into seven bands under these conditions as two, rather than the expected three, large-sized segments were resolved. Each of the in vitro cRNA segments migrated slightly faster than the corresponding vRNA segment. To determine whether this difference in mobility reflects a difference in size between cRNA and vRNA, the double-stranded RNA formed by annealing labeled in vitro cRNA to unlabeled vRNA was subjected to various nuclease treatments and was analyzed by gel electrophoresis. Hybrids treated with RNase T2 or a combination of RNase T2 and RNase H migrated slightly faster than those treated only with RNase H, indicating that RNase T2 removed an RNA sequence other than polyadenylic acid, most probably a short sequence of vRNA not hydrogen bonded to cRNA. These results suggest that the in vitro cRNA segments are shorter than, and thus incomplete transcripts of the corresponding vRNA segments. All eight hybrids were resolved by gel electrophoresis, indicating that all eight vRNA segments are transcribed into cRNA in vitro. We also present evidence suggesting that the ApG primer initiates in vitro transcription exactly at the 3' end of vRNA.

Cell-Free System↗
PubMed1980

Coding assignments of double-stranded RNA segments of SA 11 rotavirus established by in vitro translation.

The segmented double-stranded (ds) RNA genome of the simian rotavirus SA 11, after denaturation, can be translated in a cell-free protein synthesizing system. Of the 11 genome segments, 9 can be resolved on polyacrylamide gels and thus could be individually isolated and translated, providing a means of identifying the polypeptide encoded by each segment. On the basis of electrophoretic mobility of products in sodium dodecyl sulfate-polyacrylamide gels, the probable gene-coding assignments of dsRNA segments 1 to 6 were determined. RNA segments 1 to 4 code for polypeptides I1, I2, I3, and I4, respectively; segment 5 codes for a polypeptide very similar in mobility to a minor polypeptide present in SA 11-infected cells, O1A; and segment 6 codes for the major inner-capsid polypeptide I5.

Capsid↗
PubMed1982

Sequence of the long terminal repeat and adjacent segments of the endogenous avian virus Rous-associated virus 0.

Rous-associated virus 0 (RAV-0), an endogenous chicken virus, does not cause disease when inoculated into susceptible domestic chickens. An infectious unintegrated circular RAV-0 DNA was molecularly cloned, and the sequence of the long terminal repeat (LTR) and adjacent segments was determined. The sequence of the LTR was found to be very similar to that of replication-defective endogenous virus EV-1. Like the EV-1 LTR, the RAV-0 LTR is smaller (278 base pairs instead of 330) than the LTRs of the oncogenic members of the avian sarcoma virus-avian leukosis virus group. There is, however, significant homology. The most striking differences are in the U(3) region of the LTR, and in this region there are a series of small segments present in the oncogenic viruses which are absent in RAV-0. These differences in the U(3) region of the LTR could account for the differences in the oncogenic potential of RAV-0 and the avian leukosis viruses. I also compared the regions adjacent to the RAV-0 LTR with the available avian sarcoma virus sequences. A segment of approximately 200 bases to the right of the LTR (toward gag) is almost identical in RAV-0 and the Prague C strain of Rous sarcoma virus. The segment of RAV-0 which lies between the end of the env gene and U(3) is approximately 190 bases in length. Essentially this entire segment is present between env and src in the Schmidt-Ruppin A strain of Rous sarcoma virus. Most of this segment is also present between env and src in Prague C; however, in Prague C there is an apparent deletion of 40 bases in the region adjacent to env. In Schmidt-Ruppin A, but not in Prague C, about half of this segment is also present between src and the LTR. This arrangement has implications for the mechanism by which src was acquired. The region which encoded the gp37 portion of env appears to be very similar in RAV-0 and the Rous sarcoma viruses. However, differences at the very end of env imply that the carboxy termini of RAV-0, Schmidt-Ruppin A, and Prague C gp37s are significantly different. The implications of these observations are considered.

Avian Leukosis Virus↗
PubMed1991

Neuroattenuation of an avirulent bunyavirus variant maps to the L RNA segment.

The derivation and characterization of a neuroattenuated reassortant clone (RFC 25/B.5) of California serogroup bunyavirus was described previously (M. J. Endres, A. Valsamakis, F. Gonzalez-Scarano, and N. Nathanson, J. Virol. 64:1927-1933, 1990). To map the RNA segment responsible for this attenuation, a panel of reassortants was constructed between the attenuated clone B.5 (genotype TLL) and a virulent clone (B1-1a) of reciprocal genotype (LTT). Parent viruses and clones representing all of the six possible reassortants were examined for neurovirulence by intracerebral injection in adult mice. Reassortants bearing the large RNA segment from the virulent parent were almost as virulent as the virulent parent virus, while reassortants bearing the large RNA segment from the avirulent parent virus exhibited low or intermediate virulence. These results indicate that the large RNA segment is the major determinant of neuroattenuation of clone B.5. In addition to its neuroattenuation, clone B.5 was temperature sensitive and exhibited an altered plaque morphology. These phenotypes also segregated with the large RNA segment. The importance of the large RNA segment (which encodes the viral polymerase) in neurovirulence contrasts with prior studies which indicate that the ability to cause lethal encephalitis after peripheral injection of suckling mice (neuroinvasiveness) is primarily determined by the middle-sized RNA segment, which encodes the viral glycoproteins.

Animals↗