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Biomedical subjects

D Bennett

Publications and source records attributed to D Bennett.

At least 109 records · Page 6Linked to original sources
PubMed1991

Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).

Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Development of a small RGD peptide fibrinogen receptor antagonist with potent antiaggregatory activity in vitro.

The development of potent antithrombotic agents from the fibrinogen platelet receptor binding sequences Fg-alpha 572-575 -Arg-Gly-Asp-Ser- and Fg-gamma 400-411 -HHLGGAKQAGDV, believed to be a cryptic RGD-type sequence, is described. The tetrapeptide Ac-RGDS-NH2 itself is capable of inhibiting platelet aggregation in vitro at high concentrations, IC50 91.3 +/- 0.1 microM [in vitro antiaggregatory activity employing dog platelet rich plasma (PRP)/ADP], due to low platelet fibrinogen receptor affinity, Ki 2.9 +/- 1.9 microM (purified, reconstituted human platelet GPIIb/IIIa), relative to fibrinogen, Ki 38.0 +/- 6.0 nM. The peptide is also unstable to plasma, suffering total loss of in vitro activity upon incubation in PRP for 3 h (T1/2 90 min). Only modest improvements in potency were achieved with linear analogues of Ac-RGDS-NH2, while dramatic results were achieved with cyclic analogues, culminating in the cyclic disulfide Ac-cyclo-S,S-[Cys-(N alpha-Me)Arg-Gly-Asp-Pen]-NH2 (SK&F 106760) with improved plasma stability (100% activity after 3 h), affinity (Ki 58 +/- 20 nM purified human receptor), and potency (IC50 0.36 +/- 0.4 microM dog PRP/ADP). The affinity of this peptide is 2 orders of magnitude greater than that of Ac-RGDS-NH2. The affinity of the analogue is also comparable to fibrinogen. This peptide constitutes a first potent small peptide entry into the class of novel antithrombotic agents called fibrinogen receptor antagonists.

Amino Acid Sequence↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗