Canine distemper virus in bone.
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Animals↗
Biomedical subjects
D Bennett
Publications and source records attributed to D Bennett.
Testis-/embryo-expressed genes are clustered in the mouse H-2K region.
The major histocompatibility complex (MHC) of the mouse is located on chromosome 17 in the distal inversion of the t complex. In addition to genes playing major roles in the immune response, it contains a diversity of genes. In humans, numerous diseases are known to be associated with the MHC loci. Moreover, at least three recessive embryonic t-lethal mutations have been mapped to the MHC. Here a molecular genetic approach was used to study the detailed genomic structure of 240 kilobases (kb) surrounding the H-2K gene and 150 kb of a partly homologous region located in the distal inversion of the t complex. Combined with previous findings, the H-2K region was found to contain an impressively high density of genes--12 transcription units in 240 kb. Surprisingly, virtually all of these genes are expressed in testis and/or embryos. The genomic organization of this region is contrasted with the 150 kb of the homologous area where only three genes and an endogenous retrovirus reside.
Animals↗
Combination therapy with zidovudine and dideoxycytidine in patients with advanced human immunodeficiency virus infection. A phase I/II study.
OBJECTIVE: To evaluate the safety and immunologic and antiviral effects of combination therapy with zidovudine and dideoxycytidine (ddC) in patients with advanced human immunodeficiency virus type 1 (HIV) infection. DESIGN: A phase I/II open-label, dose-ranging study. SETTING: Two AIDS Clinical Trials Group units. PATIENTS: Patients (56) with advanced HIV disease. INTERVENTIONS: Patients were randomly assigned to one of three paired regimens of zidovudine and ddC. We evaluated six dosing regimens, each involving oral administration of the study drugs at 8-hour intervals. MEASUREMENTS: Pharmacokinetics, toxicity, CD4 counts, p24 antigenemia and clinical end points. MAIN RESULTS: The median follow-up period was 40.6 weeks (range, 0.3 to 70 weeks). Neither drug affected the pharmacokinetic profile of the other. Episodes of serious hematologic toxicity were infrequent, occurring in only 17.9% of patients, and did not differ among the regimens (P = 0.15). Severe sensory peripheral neuropathy occurred in two patients (one patient each in regimens 1 and 4). One patient receiving regimen 4 died. The mean maximal increase in CD4 counts exceeded 109 cells/mm3, and 69% of patients receiving combinations containing 300 or 600 mg of zidovudine daily had an increase in CD4 counts of 50 cells/mm3 or greater. Regimens containing 600 mg of zidovudine daily (regimens 2 and 5) were also more likely to result in persistent increases in CD4 counts above pretreatment values than were the two lowest dose regimens (P = 0.003). The decline in CD4 counts was more rapid, and the suppression of the p24 antigenemia was less rapid and less sustained in patients receiving the lowest zidovudine dose alone (regimen 6). The addition of ddC to regimen 6 (regimen 3) resulted in a slower decline in the CD4 counts (P = 0.06). CONCLUSIONS: Combination therapy with zidovudine and ddC at the doses tested was well tolerated and did not result in toxicity. A daily oral dose of 150 mg of zidovudine appeared to produce a suboptimal effect on p24 antigenemia and CD4 counts. Combination therapy with ddC and higher doses of zidovudine produced greater and more persistent effects in patients with advanced HIV infection compared with other study regimens and with the results of previous trials of zidovudine monotherapy.
Adult↗
Metallic foreign bodies in the mouth or pharynx of horses: seven cases (1983-1989).
Seven horses with metallic foreign bodies in the mouth or pharynx were examined at the Colorado State University Veterinary Teaching Hospital from 1983 to 1989. The horses had variable clinical signs, such as purulent nasal discharge, swelling of the throatlatch area, and dyspnea. Most of the horses had clinical signs for more than 2 weeks, and had no or only temporary improvement with conservative medical treatment (antibiotics, nonsteroidal anti-inflammatory drugs). The definitive diagnostic test in all of the cases was radiography, which also aided in the plan for surgical removal of the foreign body. Once the foreign body was removed from each of the horses, their clinical signs resolved. Most of the foreign bodies were small pieces of wire, the sources of which could not be determined, but that may have been incorporated in baled hay.
Animals↗
Detection of canine distemper virus in bone cells in the metaphyses of distemper-infected dogs.
In the light of recent evidence implicating canine distemper virus (CDV) as a possible etiologic agent in Paget's disease of bone, we thought that it would be of interest to examine distemper-infected bone in the natural host. Samples from the long bones, spleen, and bladder of four distemper-infected and three uninfected dogs were examined for the presence of CDV nucleocapsid and phosphoprotein genes and the measles virus (MV) nucleocapsid gene using the technique of in situ hybridization with radioactively labeled riboprobes. Two of the four distemper-infected dogs showed strongly positive hybridization with both of the CDV probes. The signal was present in marrow cells, in osteoblasts, in osteocytes, and particularly in osteoclasts. No hybridization was seen over the cartilage cells of the growth plate, and there was a clear line of demarcation at the point of invasion of osteoclasts and vascularization. The spleen and bladder samples from infected dogs also showed positive hybridization. There was no hybridization with the MV probe in any of the distemper-infected tissue. Samples from the uninfected dogs showed no evidence of hybridization with either the CDV or MV probes. These results show that CDV can infect bone cells of the natural host and provide further support for the theory that CDV may play a role in human Paget's disease of bone.
Animals↗
Lymphocyte populations in the synovial membranes of dogs with rheumatoid arthritis.
Lymphocyte populations in the synovial membranes of dogs with canine rheumatoid arthritis (CRA) were investigated by immunohistochemical staining techniques. T-lymphocytes were the predominant cell type distributed throughout the supporting layer of the synovial membranes. B-lymphocytes expressing IgG were seen far more commonly than those expressing either IgA or IgM. Synovial membrane biopsies from normal and osteoarthritic joints did not have the marked cellular infiltrates seen in joints with CRA. The synovial immunohistopathological features in dogs with CRA are similar to those seen in human rheumatoid arthritis.
Animals↗
Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial.
Thrombolysis of acute pulmonary embolism can be accomplished more rapidly and safely with 100 mg of recombinant human tissue-type plasminogen activator (rt-PA) (Activase) than with a conventional dose of urokinase (Abbokinase) given as a 4,400-U/kg bolus dose, followed by 4,400 U/kg per h for 24 h. To determine the effects of a more concentrated urokinase dose administered over a shorter time course, this trial enrolled 90 patients with baseline perfusion lung scans and angiographically documented pulmonary embolism. They were randomized to receive either 100 mg/2 h of rt-PA or a novel dosing regimen of urokinase: 3 million U/2 h with the initial 1 million U given as a bolus injection over 10 min. Both drugs were delivered through a peripheral vein. To assess efficacy after initiation of therapy, repeat pulmonary angiograms at 2 h were performed in 87 patients and then graded in a blinded manner by a panel of six investigators. Of the 42 patients allocated to rt-PA therapy, 79% showed angiographic improvement at 2 h, compared with 67% of the 45 patients randomized to urokinase therapy (95% confidence interval for the difference in these proportions [rt-PA minus urokinase] is -6.6% to 30.4%; p = 0.11). The mean change in perfusion lung scans between baseline and 24 h was similar for both treatments. Three patients (two treated with rt-PA and one with urokinase) had an intracranial hemorrhage, which was fatal in one. The results indicate that a 2-h regimen of rt-PA and a new dosing regimen of urokinase exhibit similar efficacy and safety for treatment of acute pulmonary embolism.
Acute Disease↗
Adolescent health--a time for action.
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Adolescent↗
Fluid balance in elderly patients following acute stroke.
We studied the relationship between plasma osmolality, arginine vasopressin (AVP), and fluid input in patients during the acute phase of a first stroke. Fifteen consecutive patients were studied (median age 79) and their blood sampled on days 0, 1, 2, 3, 7 and 14. Plasma osmolality was related to fluid input over days 0-3 (p = 0.0013) and AVP over 14 days (p less than 0.001). Patients with a poor outcome had higher AVP concentrations (p = 0.02). Those on intravenous fluids received a higher volume (p less than 0.01) and had a lower plasma osmolality (p = 0.04). The results of this preliminary study indicate that a standard regime for fluid input is inappropriate.
Aged↗
Vulvovaginitis and vaginal pH.
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Age Factors↗
Influence of age on the relation between heart rate variability, left ventricular ejection fraction, frequency of ventricular extrasystoles, and sudden death after myocardial infarction.
AIMS: To examine the influence of age on the prediction of sudden death after acute myocardial infarction based on heart rate variability (HRv), left ventricular ejection fraction (LVEF), and the frequency of ventricular extrasystoles. BACKGROUND: Autonomic and left ventricular function and the frequency of ventricular extrasystoles change with age but the influence of age on the prediction of sudden death from these variables has not been examined. METHODS: The 477 patients who had been through an early postinfarction risk stratification protocol and followed up for a mean of 790 days were dichotomised at 60 years of age. RESULTS: Sudden deaths occurred with similar frequency in both age groups (12 (4.7%) of the 256 patients aged < 60 years and seven (3.2%) of the 221 older patients). Sudden death, however, accounted for 52% of all deaths in the young group but only 18.4% of all deaths in the older group (p < 0.01). An HRv index of < 20 units combined with an average of more than 10 ventricular extrasystoles an hour on Holter monitoring (VE10) had a sensitivity of 50%, a positive predictive accuracy of 33%, and a risk ratio of 18 in the young group (p < 0.001) but was not significantly predictive in older patients. The situation was similar when the combination of an LVEF < 40% with VE10 was considered. This combination had a sensitivity of 44%, positive predictive accuracy of 36.4%, and a risk ratio of 16.1 in young patients (p < 0.001), but was not significantly predictive in older patients. The combination of VE10 with either LVEF < 40% or HRv < 20 units gave a sensitivity of 75%, positive predictive accuracy of 30%, and a risk ratio of 30 in young patients (p < 0.001), but the relation between this combination and sudden death in older patients was not statistically significant. CONCLUSION: In postinfarction patients aged < 60 sudden death was a more predominant mode of death and was more reliably predicted from a depressed HRv index, an LVEF < 40%, and VE10 than in older postinfarction patients. These findings may have important implications for post-infarction risk stratification and management.
Age Factors↗
The dependency of oxygen consumption on oxygen delivery in critically ill postoperative patients is mimicked by variations in sedation.
The finding of a dependence of oxygen consumption on oxygen delivery in critically ill patients has encouraged interventions to increase oxygen delivery index (DO2I) to overcome tissue hypoxia. In individuals other factors may influence oxygen consumption index (VO2I) and DO2I and may cause an apparently dependent relationship. We studied the effects of sedation and temperature on the VO2I/DO2I relationship in 13 perioperative patients. Pooled data showed significant correlations between VO2I and DO2I (r greater than 0.6, p less than 0.05) but also between VO2I and sedation score (r greater than 0.7, p less than 0.05), but not VO2I and temperature (r less than 0.5). When VO2I was standardized for the effects of sedation score (SS), the relationship between VO2I and DO2I was lost (r less than 0.5). Seven of 13 patients had significant (p less than 0.05) correlations between VO2I and SS and six of 13 between VO2I and DO2I; when standardized for the effect of varying sedation, no relationships were significant. When interpreting oxygen transport data from critically ill patients, the effects of sedation but not temperature must be taken into account; otherwise a false impression of a dependent relationship between VO2I and DO2I may cause unnecessary treatment.
Biological Transport↗
Lassa fever encephalopathy: clinical and laboratory findings.
Clinical and laboratory findings are reported in nine patients who developed acute encephalopathy during the course of Lassa fever. The encephalopathy manifested 3-17 days after disease onset with confusion, followed rapidly by tremor (seven patients), grand mal convulsions (seven), abnormal posturing (three) and coma (eight); focal neurological signs and evidence of raised intracranial pressure were not seen. Eight patients died, most commonly from respiratory arrest following a protracted fit. Development of encephalopathy did not correlate with the presence of virus in cerebrospinal fluid (CSF), nor with virus antibodies in CSF and/or serum; thus, neither direct cytopathic nor immune-mediated mechanisms seem to be involved in its pathogenesis.
Adolescent↗
The effects of density fluctuations on the partitioning of foreign molecules into lipid bilayers: application to anaesthetics and insecticides.
An extensive computer-simulation study is performed on a simple but general molecular model recently proposed (Jørgensen et al. (1991) Biochem. Biophys. Acta 1062, 277-238) to describe foreign molecules interacting with lipid bilayers. The model is a multi-state lattice model of the main bilayer transition in which the foreign molecules are assumed to intercalate at interstitial lattice positions. Specific as well as non-specific interactions between the foreign molecules and the lipid acyl chains are considered. Particular attention is paid to the fluctuating properties of the membrane and how the presence of the foreign molecules modulates these fluctuations in the transition region. By means of computer-stimulation techniques, a detailed account is given of the macroscopic as well as microscopic consequences of the fluctuations. The macroscopic consequences of the fluctuations are seen in the thermal anomalies of the specific heat and the passive trans-membrane permeability. Microscopically, the fluctuations manifest themselves in lipid-domain formation in the transition region which implies an effective dynamic membrane heterogeneity. Within the model it is found that certain anaesthetics and insecticides which are characterised by specific interactions with the lipids have a strong effect on the heterogeneity of the membrane inducing regions of locally very high concentration of the foreign molecules. This leads to a broadening of the specific heat peak and a maximum in the membrane/water partition coefficient. These results are in accordance with available experimental data for volatile general anaesthetics like halothane, local anaesthetics like cocain derivatives, and insecticides like lindane.
Anesthetics↗
Clinical use of intravascular oxygenation.
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Aged↗
A general model for the interaction of foreign molecules with lipid membranes: drugs and anaesthetics.
A general microscopic interaction model is proposed to describe the changes in the physical properties of phospholipid bilayer membranes due to foreign molecules which, to different degrees, partition between the membrane phases and the aqueous environment. The model is a multi-state lattice model for the main phase transition of lipid bilayers and the foreign molecules are assumed to intercalate as interstitials in the lattice. By varying the model parameters, the diversity in the thermodynamic properties of the model is explored using computer-simulation techniques which faithfully take account of the thermal fluctuations. The calculations are performed in both the canonical and the grand canonical ensembles corresponding to the cases where the concentration of foreign molecules in the membrane is either fixed or varies as the external conditions are changed. A classification of the diverse thermal behaviour, specifically with regard to the phase diagram, the specific heat, the density fluctuations, and the partition coefficient, is suggested with a view to rationalizing a large body of experimental measurements of the effects of different foreign molecules on membrane properties. The range of foreign molecules considered includes compounds as diverse as volatile general anaesthetics like halothane, cocaine-derived local anaesthetics like procaine, calcium-channel blocking drugs like verapamil, antidepressants like chlorpromazine, and anti-cancer agents like adriamycin.
Anesthetics↗
Several testis-expressed genes in the mouse t-complex have expression differences between wild-type and t-mutant mice.
The t-complex of the mouse occupies the proximal half of chromosome 17 and contains genes which have profound effects on spermatogenesis. Mutations of several loci in the t-complex appear to interact to cause male sterility or transmission ratio distortion (TRD). By cDNA screening or chromosomal walking we have identified seven genes, which are expressed in the germ cells of testis and map to various regions of the t-complex. These genes were named t-complex testis-expressed (Tctex) genes. An analysis of their expression patterns in testes from +/+, +/t, and t/t mice was done by in situ hybridization and by northern blotting. Six genes begin to be expressed at the pachytene stage: Three of them are more abundant at pachytene stage, while three others are more abundant at postmeiotic stages. One gene is expressed at all the stages of spermatogenesis. Interestingly, four Tctex genes show differences in the amount of transcript between wild-type and t-mutant testes. The chromosomal location and expression pattern imply that Tctex genes might be candidate genes for sterility or TRD.
Animals↗
Molecular organization of the D-Qa region of t-haplotypes suggests that recombination is an important mechanism for generating genetic diversity of the major histocompatibility complex.
We have determined the molecular maps of the H-2D and Qa regions of the t-complex haplotypes t12 and tw5 by chromosomal walking. Analysis with class I probes and other probes unique to the H-2D:Qa subregion indicates that the class I gene organization of t12 is: D1-D2-Q1-Q2-Q3-Qx-Q4-Q5-Q10, while that of tw5 is: D1-D2-Q1-Q2-Q4-Q5-Q10. Thus, the absence of the Q6-Q9 genes suggested previously in t-haplotypes was confirmed. A comparison of the molecular maps of the t12 and tw5 chromosomes revealed an extremely mosaic pattern of diversity: The regions between D1 and D2, and between Q4 and Q10, are very similar in both chromosomes. However, their Q1 to Q3 regions are strikingly different. Further comparisons of wild-type chromosomes and additional t-haplotypes by molecular mapping and genomic Southern blot hybridization with probes to the Q1-Q3 region showed a high level of polymorphism among both wild-type chromosomes and among t-haplotypes. The characteristics of the polymorphisms suggest that recombination may play an important role in generating this genetic diversity. Furthermore, recombination between wild-type and t-haplotype chromosomes may be involved.
Animals↗