Molecular cloning and sequence analysis of the fusion glycoprotein gene of human parainfluenza virus type 2

A cDNA clone containing a 2.0-kb insert was identified as the human parainfluenza virus type 2 (PI2) fusion glycoprotein gene by hybridizing with a viral RNA probe and a synthetic oligonucleotide derived from a conserved sequence found in other paramyxovirus fusion protein genes. The complete nucleotide sequence of the glycoprotein gene was determined by the dideoxynucleotide sequencing procedure and found to contain a single, large open reading frame encoding a protein of 551 amino acids with a calculated molecular weight of 59,664. Comparison of the P12 fusion protein with those of other paramyxoviruses indicated similarities in overall length, N-terminal signal peptide sequence (amino acids 7 to 25), C-terminal membrane-spanning region (amino acids 486 to 513), and a highly conserved fusion sequence region at the N-terminus of the F1 subunit (amino acids 107 to 132).     

Frequent deletions in nine newly immortal human cell lines.

Nine newly immortal lines of human fibroblasts transfected with SV40 T antigen were examined for recurrent chromosome losses. In order of decreasing frequency, all nine lines had three or more of the following minimal deletions specifically associated with the immortalization event: del(6)(q21), del(3)(p24), del(1)(p34), del(4)(p25), del(5)(p14), del(11)(p11), del(11)(q14), del(12)(p12), and del(14)(p?). Many other chromosome changes were not clearly associated with immortalization, but were acquired during other stages of this multistep model of neoplastic transformation. We propose that these chromosome loci associated with immortalization are candidates for the location of genes involved in cellular senescence.     

Biodegradation studies on periodate oxidized cellulose

Sodium periodate oxidized cellulose was found to degrade into small molecules when implanted subcutaneously in rats. Thus the potentiality of using oxidized cellulose as a biodegradable drug carrier is envisaged.     

Replacing the academic medical center's teaching hospital.

Addressing the need for updated teaching hospital facilities is one of the most significant issues that an academic medical center faces. The authors describe the process they underwent in deciding to build a new facility at the Medical University of South Carolina (MUSC). Initial issues included whether or not the teaching hospital would continue to play a role in clinical education and whether to replace or renovate the existing facility. Once the decision to build was reached, MUSC had to choose between an on-campus or distant site for the new hospital and determine what the function of the old hospital would be. The authors examine these questions and discuss the factors involved in different stages of decision making, in order to provide the academic medicine community guidance in negotiating similar situations. Open communication within MUSC and with the greater community was a key component of the success of the enterprise to date. The authors argue that decisions concerning site, size, and focus of the hospital must be made by developing university-wide and community consensus among many different constituencies. The most important elements in the success at MUSC were having unified leadership, incorporating constituent input, engaging an external consultant, remaining unfazed by unanticipated challenges, and adhering to a realistic, aggressive timetable. The authors share their strategies for identifying and successfully managing these complex and potentially divisive aspects of building a new teaching hospital.     

Scanning electron microscopic characterization of healing and normal rat ligament microstructure under slack and loaded conditions

The objective of this study was to observe and compare behavior of the collagen fiber microstructure in normal and healing ligaments, both in situ and ex vivo, in order to add insight into the structure-function relationship in normal and healing ligaments. Fifty-two ligaments from 26 male rats were investigated. Eleven animals underwent surgical transection of both medial collateral ligaments (MCLs) (22 ligaments), which were allowed to heal for a period of 2 weeks. An additional 15 animals (30 ligaments) were used as normals. Ligaments were placed into six groups: Slack (n = 6 control, n = 6 healing), Reference (n = 4 control, n = 4 healing), Loaded (n = 4 control, n = 4 healing), 15 degrees Flexion (n = 4 control, n = 4 healing), 120 degrees Flexion (n = 4 control, n = 4 healing), and Tissue Strain vs. Flexion Angle (n = 8 normals). All ligaments, except those in the Tissue Strain vs. Flexion Angle group, were prepared for scanning electron microscopy. Tissues were harvested, mounted in a load frame, and chemically fixed in one of five states: (1). slack, (2). reference (onset of loading), (3). loaded, (4). 15 degrees knee flexion, or (5). 120 degrees knee flexion. After fixation the tissues were prepared for electron microscopy (SEM). The micrographs from the slack, reference, and loaded groups show fiber straightening with loading in normal ligaments as well as in both scar and "retracted" regions of healing ligaments. Collagen fibers' diameter and crimp patterns were dramatically changed in the scar region of healing ligaments: Width decreased from 19.4 +/- 1.7 microm to 6.5 +/- 2.1 microm (p <.000001), period from 51.4 +/- 15.1 microm to 11.0 +/- 2.4 microm (p <.000001), and amplitude from 9.8 +/- 0.8 microm to 3.9 +/- 0.8 microm (p <.000001). Normal ligaments fixed in situ show wavy regions at 120 degrees but less so at 15 degrees flexion. Healing ligaments fixed in situ show regions of fiber waviness in the scar region at 120 degrees and also at 15 degrees flexion, indicating ligament laxity persists toward both extremes of the range of motion. The data suggest that straightening of crimped fibers is a functionally relevant phenomenon, not only in normal but also in healing ligaments.     

Noradrenergic mechanisms in the central amygdalar nucleus and gastric stress ulcer formation in rats

Microinjections of noradrenaline (NA, 0.3, 3.0 and 30.0 micrograms) into the central amygdalar nucleus (CEA) produced dose-related attenuations of cold restraint (3 h at 4 degrees C) induced gastric ulcer formation in rats. On the other hand, stress ulcer aggravating effects were seen with beta-adrenoceptor antagonist, propranolol (10 micrograms) but not with the alpha-adrenoceptor antagonist, prazosin (1 and 10 micrograms). Moderate enhancements of gastric stress lesions were also seen with the NA release inhibitor clonidine (1 microgram) and the neurotoxin DSP-4 (25 micrograms). Further, pretreatment of rats with intra-amygdalar (i.am.) propranolol but not prazosin, antagonized and reversed the gastric cytoprotective effects of NA. The results indicate that beta-adrenoceptor-mediated NAergic mechanisms at the level of the CEA are important for the maintenance of gastric mucosal integrity during immobilization stress.     

Mapping of X-linked progressive retinal atrophy (XLPRA), the canine homolog of retinitis pigmentosa 3 (RP3)

X-linked progressive retinal atrophy (XLPRA) in the Siberian husky dog is a naturally occurring X-linked retinopathy closely resembling X-linked retinitis pigmentosa (XLRP) in humans. In affected males, initial degeneration of rods is followed by cone degeneration and complete retinal atrophy; carrier females have random patches of rod degeneration consistent with random X chromosome inactivation. By typing the XLPRA pedigree with five intragenic markers [dystrophin, retinitis pigmentosa GTPase regulator ( RPGR ), tissue inhibitor of metalloproteinases 1, androgen receptor and factor IX], we established a linkage map of the canine X chromosome, and confirmed that the order of these five genes is identical to that on the human X. XLPRA was tightly linked to an intragenic RPGR polymorphism (LOD 11.7, zero recombination), thus confirming locus homology with RP3. We cloned the full-length canine RPGR cDNA and three additional splice variants. No disease-causing mutation was found in the RPGR-coding sequence of the four splice variants characterized, a finding similar to approximately 80% of human XLRP patients whose disease maps to the RP3 locus. In addition, there were no significant differences in the proportional expression of each splice variant in normal and pre-degenerate XLPRA-affected retina. Expression of all RPGR splice variants increased later in the disease, when retinas were undergoing active degeneration. The results provide further evidence of cross-species retention of a complex splicing pattern in the 3' portion of RPGR, the functional significance of which is unknown. In addition, the possibility of another disease locus in the RP3 region is supported.     

Fra(2) (q13) and inv(9) (p11q12) in autism: causal relationship?

Twenty individuals with autism or related disorders underwent chromosome analysis and physical examinations with documentation of minor anomalies. Chromosome anomalies were identified in 3: 2 had the heritable folate sensitive fra(2) (q13) site and 1 had an inv(9) (p11q12). No heritable chromosome variants or anomalies were seen in 20 age and sex-matched control individuals. When patients with the fra(2) were excluded from analyses, there was no difference in the frequency of chromosome breaks and/or gaps between the study group and control group. The results of this study suggest that heritable folate sensitive fragile sites and other chromosome variants may be more commonly seen in individuals with autism or related disorders in childhood than in the general population.     

P300 and Stimulus Categorization: Two Plus One is not so Different from One Plus One

Event related brain potentials (ERPs) were recorded from subjects who were instructed to count one of three, equally probable tones presented in a random sequence. In another condition, the subjects had to count one of two stimuli, one of which was presented with a probability of .33. The data support the view that the pattern of variation of P300 amplitude with the sequential structure of the series depends on the category to which events are assigned, rather than on the individual stimuli eliciting the P300. Furthermore, the data support the idea that the amplitude of P300 elicited by task-relevant stimuli is determined by the subjective probability associated with the eliciting event. DESCRIPTIONS: ERP, P300, Subjective probability, Stimulus categorization.