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Biomedical subjects

D Bennett

Publications and source records attributed to D Bennett.

At least 91 records · Page 5Linked to original sources

Anesthetics affect membrane heterogeneity.

A computer-simulation study is performed on a simple but general molecular model of the interaction of general and local anesthetics with lipid membranes. In the neighborhood of the gel-to-fluid membrane phase transition it is found that anesthetics have a strong effect on the heterogeneity of the membrane-inducing regions of locally high anesthetics concentration. 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 anesthetics like halothane and local anesthetics like cocaine derivatives.

1,2-Dipalmitoylphosphatidylcholine

Glycosaminoglycans in horses with osteoarthritis.

Horse articular cartilage glycosaminoglycans (GAGs) were measured in synovial fluids from 48 joints affected with osteoarthritis (OA), 22 normal joints, four joints with osteochondritis, three joints with traumatic arthritis and seven joints infected with bacteria. Serum and urine from individual horses were also examined for the presence of GAGs. High levels of GAGs were found in synovial fluids (SF) from horses with OA. In each case, the level was higher in the synovial fluid than in the serum or urine from the same horse. Horses with OA showed high GAG levels in SF, serum and urine compared to horses with normal and infected joints. High levels were also found in horses with osteochondritis and traumatic arthritis. Levels of synovial fluid GAG reflect cartilage destruction in arthritis and may be useful for monitoring disease progression in the equine species.

Animals

Exchange transfusion of a patient with fulminant Lassa fever.

We report a patient with fulminant Lassa fever who responded dramatically to a 2.5-litre exchange transfusion of whole blood. On admission he was semicomatose with facial oedema and oral haemorrhage; his platelets showed markedly depressed aggregation to ADP; and his plasma inhibited the aggregation responses of normal platelets in vitro. Exchange transfusion resulted in rapid clinical improvement, recovery of platelet function, and disappearance of platelet-inhibitory activity in plasma. The patient died 2 weeks later from an acute encephalopathy. His initial response was sufficiently impressive to suggest that further evaluation of this therapeutic approach is justified in selected patients with overwhelming Lassa virus infection.

Adult

Stress hormone and blood glucose response following acute stroke in the elderly.

We studied the relation of reactive hyperglycemia, stress hormone response, and outcome in 23 consecutive elderly patients (median age 80 [range 75-92] years) following an acute first stroke. The median delay from the onset of the stroke to the first blood sample (day 0) was 9 (range 4-22) hours. Subsequent blood samples were taken, after fasting, for the determination of blood glucose, cortisol, catecholamine, insulin, C-peptide, glucagon, and lactate concentrations on days 1, 2, 3, 7, 14, 30, and 90. For all 23 patients, a significant relation was found between the blood glucose concentration and survival (p = 0.03) and the blood glucose concentration decreased with time (p less than 0.001). There was also a significant relation between blood glucose concentration and outcome (p = 0.02). For the 15 patients with complete data, the major determinants of the blood glucose concentration were the cortisol, insulin, and glucagon concentrations (all p less than 0.001), which accounted for 42% of the variance. When all the indexes were analyzed together by logistic regression, only the cortisol concentration was related to outcome (p = 0.02). Hyperglycemia following a stroke probably reflects the intensity of the stress hormone response. We have confirmed that hyperglycemia is a predictor of outcome in persons with stroke.

Acute Disease

Submegabase clusters of unstable tandem repeats unique to the Tla region of mouse t haplotypes.

We describe here the identification and genomic organization of mouse t haplotype-specific elements (TSEs) 7.8 and 5.8 kb in length. The TSEs exist as submegabase-long clusters of tandem repeats localized in the Tla region of the major histocompatibility complex of all t haplotype chromosomes examined. In contrast, no such clusters were detected among 12 inbred strains of Mus musculus and other Mus species; thus, clusters of TSEs represent the first absolutely qualitative difference between t haplotypes and wild-type chromosomes. Pulsed field gel electrophoresis shows that the number of clusters, and the number of repeats in each cluster are extremely variable. Dramatic quantitative differences of TSEs uniquely distinguish every independent t haplotype from any other. The complete nucleotide sequence of one 7.8-kb TSE reveals significant homology to the ETn (a major transcript in the early embryo of the mouse), and some homologies to intracisternal A-particles and the mammary tumor virus env gene. Apart from the diagnostic relevance to t haplotypes, evolutionary and functional significances are discussed with respect to chromosome structure and genetic recombination.

Animals

Genetic and molecular analysis of the proximal region of the mouse t-complex using new molecular probes and partial t-haplotypes.

The t-complex is located on the proximal third of chromosome 17 in the house mouse. Naturally occurring variant forms of the t-complex, known as complete t-haplotypes, are found in wild mouse populations. The t-haplotypes contain at least four nonoverlapping inversions that suppress recombination with the wild-type chromosome, and lock into strong linkage disequilibrium loci affecting normal transmission of the chromosome, male gametogenesis and embryonic development. Partial t-haplotypes derived through rare recombination between t-haplotypes and wild-type homologs have been critical in the analysis of these properties. Utilizing two new DNA probes. Au3 and Au9, and several previously described probes, we have analyzed the genetic structure of several partial t-haplotypes that have arisen in our laboratory, as well as several wild-type chromosomes deleted for loci in this region. With this approach we have been able to further our understanding of the structural and dynamic characteristics of the proximal region of the t-complex. Specifically, we have localized the D17Tul locus as most proximal known in t-haplotypes, achieved a better structural analysis of the partial t-haplotype t6, and defined the structure and lethal gene content of partial t-haplotypes derived from the lethal tw73 haplotype.

Animals

Cartilage breakdown in equine osteoarthritis: measurement of keratan sulphate by an ELISA system.

Degradation of cartilage in osteoarthritis of man results in the release of sulphated glycosaminoglycans, particularly keratan sulphate, into tissue fluids. A study was made to evaluate these markers for osteoarthritis in the horse. Synovial fluid and serum levels of keratan sulphate, measured by an ELISA-inhibition technique, and sulphated glycosaminoglycans measured by specific dye binding assay, were found to be significantly increased (P less than 0.001) in joints from horses with osteoarthritis, compared with normal joints. Synovial fluids from joints with infective arthritis also showed high keratan sulphate levels, but statistically were not significantly different from osteoarthritis. Measurement of serum/synovial fluid levels of proteoglycan may enable cartilage degeneration to be detected and monitored and help more effective treatments to be developed in the equine species.

Animals

tctex-1: a candidate gene family for a mouse t complex sterility locus.

The t complex of the mouse has an important role in male germ cell development and function. Multiple mutations in the t complex interact to alter profoundly the transmission ratio of t complex-bearing sperm or to cause complete sterility or semisterility. We have isolated a multigene family, tctex-1, by screening a testicular cell cDNA library with two reciprocally subtracted testicular cDNA probes. The tctex-1 gene family produces an abundant, virtually germ cell-specific transcript that is 8-fold overexpressed in t homozygotes. The aberrant expression of tctex-1 is solely dependent on the t haplotype genes and occurs only in germ cells. The chromosomal location and pattern of expression of tctex-1 make it a candidate for involvement in male sterility.

Amino Acid Sequence

Optimisation of positive and expiratory pressure for maximal delivery of oxygen to tissues using oesophageal Doppler ultrasonography.

OBJECTIVE: To assess oesophageal Doppler ultrasonography as a convenient means of optimising positive end expiratory pressure for maximal delivery of oxygen to tissues. DESIGN: Measurements of blood flow, arterial oxygen saturation, and cardiac output by thermodilution (when available) at baseline and at 20-30 minutes after each incremental increase (2.5-5.0 cm H2O) in positive and expiratory pressure to a maximum of 20.0 cm H2O. If the cardiac output fell by more than 15% measurements were repeated after stepwise decreases in positive end expiratory pressure. No other manoeuvre such as endotracheal suction or changing ventilator settings, drug or fluid dosage, or the patient's position was performed for at least one hour before the start of the study or during it. SETTING: Intensive care unit. PARTICIPANTS: 10 Patients being mechanically ventilated for acute respiratory failure who had stable haemodynamic and blood gas values and required a fractional inspired oxygen concentration of greater than or equal to 0.45. They were assessed on a total of 11 occasions. INTERVENTIONS: Incremental increases in positive end expiratory pressure followed when indicated by stepwise decreases. END POINT: The positive end expiratory pressure providing maximal delivery of oxygen to tissues. MEASUREMENTS AND MAIN RESULTS: Arterial oxygen saturation increased with positive end expiratory pressure in all patients by an average of 6.1%. In nine of the 11 studies, however, cardiac output fell by 15% to 30% after the second increment. On the two other occasions cardiac output and oxygen delivery rose by up to 54%. Positive end expiratory pressure was decreased on seven occasions; there was considerable individual variation in the time taken for cardiac output to rise and arterial oxygen saturation to fall. In six patients good agreement was seen between the results from Doppler ultrasonography and thermodilution, the mean of the differences being -0.3% with narrow limits of agreement (-14.4% to 13.9%). CONCLUSIONS: Oesophageal Doppler ultrasonography is a rapid, safe, and reliable technique for optimising positive end expiratory pressure to obtain maximal delivery of oxygen to tissues. The results show the need to consider haemodynamic consequences when altering positive end expiratory pressure.

Acute Disease

Detection of feline calicivirus antigens in the joints of infected cats.

Twelve specific pathogen free cats were used to investigate the role of calicivirus in causing lameness. These were divided into two groups each of six cats; one group of cats had previously been vaccinated, the other had not. Three cats in each group were given live vaccine virus (F9 related) by the subcutaneous route and two in each group were challenged intranasally with field virus (A4), either four or seven days before euthanasia. The other two cats were controls. Virus was isolated from the oropharynx of five cats and the conjunctiva of a single cat. Four of these cats had been given the field virus and two the vaccine strain; the latter two cats had been previously immunised and had high circulating neutralising antibodies to calicivirus. No virus was isolated from the joints of any cat but immunofluorescence examination revealed viral antigens within the synovial macrophages of 14 joints from five cats, three having been given the field virus and two the vaccine virus seven days before euthanasia. Immunofluorescence also demonstrated the presence of immunoglobulin and complement within synovial macrophages suggesting that the virus was in the form of an immune complex. No lameness was reported in any cat and the synovial histological changes were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Set of proteins shows abnormal posttranslational modification in embryos homozygous for dominant T-mutations.

T and Tc are dominant mutations in the mouse that affect neuroaxial development when heterozygous and cause embryonic death when homozygous. Embryos were analyzed individually by two-dimensional gel electrophoresis at 9 1/2 days gestation, 1 day before homozygotes die in utero. A comparison of the protein patterns of mutant homozygotes with those of their littermates revealed a set of proteins (T-proteins) that showed isoelectric point (pl) polymorphism. All the T-proteins were more basic in mutant homozygotes. These polymorphisms could be detected, although they were less pronounced, in embryos as young as 7 1/2-day presomite stages, when it is impossible to distinguish homozygous mutants grossly. Interestingly, the same proteins show a pl shift from basic to acidic in wild-type embryos during development from 7 1/2 to 9 1/2 days. Thus, it appears that in T and Tc mutants a developmentally specific posttranslational acidic modification of these proteins is disturbed. The likely cause of the abnormality is a defect in some mechanism for phosphorylation, since the T-proteins of wild-type embryos were shifted to higher pls by phosphatase treatment. This disturbance appears to be localized to axial structures (neural tube, somites, and surrounding mesenchyme) since only these structures, and not the rest of the mutant homozygous embryos, contain abnormally basic T-proteins.

Animals

A mouse model for neural tube defects: the curtailed (Tc) mutation produces spina bifida occulta in Tc/+ animals and spina bifida with meningomyelocele in Tc/t.

Curtailed (Tc), a dominant mutation on mouse chromosome 17, causes a tailless phenotype and occasional hindlimb paralysis in heterozygotes. Histologically, Tc/+ embryos show a variety of abnormalities including budding and ventral duplication of the developing spinal cord, duplication and intermittent absence of the notochord, and partial or complete absence of bony vertebrae, all posterior to midliver level. When Tc is heterozygous with t-haplotypes that contain the "tail interaction factor," tct, the phenotype is more severe, and a dorsal blood blister exists in the lumbosacral area. Our microscopic observations reveal that Tc/tw5 mice have a lumbosacral spina bifida with meningomyelocele. This results from the absence of bony vertebrae, extensive thinning of the dermis dorsally, and the rupturing of the previously closed neural tube, probably by increased cerebrospinal fluid (CSF) pressure on the necrotic, attenuated roof plate. Thinning of the roof plate, which facilitates the rupturing of the spinal cord, is not observed in Tc/+, which suggests that this phenomenon is associated with the interaction of Tc with the t-allele. Later in the development of Tc/tw5 embryos, adjacent blood vessels are ruptured, resulting in hemorrhage into the CSF space to give the external appearance of a blood blister. Tc/+ mice also show an absence of bony vertebrae dorsally in the lumbosacral region, but they lack the dorsal blood blister, and the dermal layer overlying the bony defect retains its normal thickness; these observations describe a spina bifida occulta.

Animals