Cell disruption: breaking up is hard to do.
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Cell Fractionation↗
Biomedical subjects
D Foster
Publications and source records attributed to D Foster.
Job-sharing: an innovative approach for administration.
A job-sharing arrangement for the Assistant Directors of Physiotherapy at the Royal Jubilee Hospital proved to be an innovative and successful experience demonstrating the feasibility of job-sharing at administrative levels in rehabilitation. Physiotherapy is traditionally a female dominated profession. By the time therapists are most highly skilled and clinically experienced, they have arrived at prime marriage and child-bearing years. Many valuable members are lost to the profession each year as therapists leave the work force to take care of their families, continue their education and participate in recreational activities. Alternative employment opportunities are needed to retain and return therapists to the work force. Convenience of work time is often important. Financial expectations may become a secondary consideration. A search of the literature revealed that while job-sharing has much to recommend it, it is not yet generally accepted in most health professional situations. A few anecdotal references described job-sharing in nursing. An industry-wide literature search revealed few references to the application of job-sharing at administrative levels.
British Columbia↗
Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10.
Glutamic acid decarboxylase (GAD; glutamate decarboxylase, L-glutamate 1-carboxy-lyase, EC 4.1.1.15), which catalyzes formation of gamma-aminobutyric acid from L-glutamic acid, is detectable in different isoforms with distinct electrophoretic and kinetic characteristics. GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent diabetes mellitus. Despite the differing GAD isoforms, only one type of GAD cDNA (GAD-1), localized to a syntenic region of chromosome 2, has been isolated from rat, mouse, and cat. Using sequence information from GAD-1 to screen a human pancreatic islet cDNA library, we describe the isolation of an additional GAD cDNA (GAD-2), which was mapped to the short arm of human chromosome 10. Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different from that detected by GAD-1. GAD-2 recognizes a 5.6-kilobase transcript in both islets and brain, in contrast to GAD-1, which detects a 3.7-kilobase transcript in brain only. The deduced 585-amino acid sequence coded for by GAD-2 shows less than 65% identity to previously published, highly conserved GAD-1 brain sequences, which show greater than 96% deduced amino acid sequence homology among the three species. The function of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined.
Amino Acid Sequence↗
Paradoxical shortening of scrapie incubation times by expression of prion protein transgenes derived from long incubation period mice.
Prolonged incubation times for experimental scrapie in I/LnJ mice are dictated by a dominant gene linked to the prion protein gene (Prn-p). Transgenic mice were analyzed to discriminate between an effect of the I/LnJ Prn-pb allele and a distinct incubation time locus designated Prn-i. Paradoxically, 4 independent Prn-pb transgenic mouse lines had scrapie incubation times shorter than nontransgenic controls, instead of the anticipated prolonged incubation periods. Aberrant or overexpression of the Prn-pb transgenes may dictate abbreviated incubation times, masking genuine Prn-p/Prn-i congruence; alternatively, a discrete Prn-i gene lies adjacent to Prn-p.
Animals↗
Effect of 12 and 20 weeks of resistance training on lumbar extension torque production.
This study compared the effect of varied training frequencies on the development of isometric lumbar extension torque (strength) over 12- and 20-week training periods. Fifty-six subjects were randomly assigned to training once every other week (training group 1, n = 10), once per week (training group 2, n = 12), twice per week (training group 3, n = 12), or three times per week (training group 4, n = 7) or to a nontraining control group (n = 15). Training consisted of one set of 8 to 12 variable-resistance lumbar extensions to volitional muscular fatigue. Prior to and following 12 and 20 weeks of training, subjects were given a test that evaluated isolated isometric lumbar extension torque in a seated position at seven positions (angles) through a 72-degree range of motion. The control group showed no change in isometric torque. All training groups showed significant increases in lumbar extension torque at 12 and 20 weeks of training, whereas no significant differences were found among the groups with respect to the magnitude of torque gained. Pooled training showed a significant time x angle interaction at 12 weeks and a continuing trend at 20 weeks, indicating that the shape of the isometric torque-angle curve changed as a result of training. This effect was due to greater increases in isometric torque at the fully extended position than at the fully flexed position at 12 weeks (92% versus 16%, respectively) and at 20 weeks (123% versus 17%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Spontaneous neurodegeneration in transgenic mice with prion protein codon 101 proline----leucine substitution.
Gerstmann-Sträussler-Scheinker syndrome (GSS) is an autosomal, dominantly inherited, human neurodegenerative disease that can sometimes be transmitted to non-human primates and rodents through intracerebral inoculation of brain homogenates from patients. Recent studies of GSS demonstrated significant genetic linkage between GSS and a leucine substitution at codon 102 of the human prion protein (PrP) gene. Transgenic mice were created to test the biologic activity of this mutation. Spontaneous neurologic disease with spongiform degeneration developed in one of three lines of transgenic mice containing murine PrP genes with a leucine substitution at codon 101 (homologous to codon 102 in humans). Transmission studies of brain homogenates from affected mice are in progress. These results indicate that some of the clinical and pathologic features of GSS can be reproduced in a transgenic mouse paradigm; this represents the first time a dominantly inherited, neurodegenerative process similar to a human disease has been genetically modeled in an experimental animal (Hsiao and Prusiner 1990).
Amino Acid Sequence↗
The Mercy Hospital, Port Huron project.
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Hospital Bed Capacity, 100 to 299↗
Adenocarcinoma of the small intestine in Crohn's disease: a unique finding.
Development of adenocarcinoma of the small bowel is rare. We present this report of a patient with a long-standing history of Crohn's disease who was found to have the 95th reported case of adenocarcinoma developed in the presence of Crohn's. The unique feature of this case is the finding of two distinctly separate carcinomas in the same surgical specimen. With report of this case and a review of the literature, certain characteristics are presented in hopes of raising suspicions sufficiently to detect this malady at an earlier stage.
Adenocarcinoma↗
Acute upper gastrointestinal haemorrhage in a district general hospital: audit of an agreed management policy.
All patients from an unselected population admitted with acute upper gastrointestinal (GI) haemorrhage to a District General Hospital (DGH) were studied prospectively over one year. Before the study period a management policy was agreed between physicians and surgeons. One-hundred-and-nine patients were admitted. Sixty-eight per cent were over 60 and 17% over 80 years of age. Sixty patients bled from peptic ulcers and seven patients rebled. Endoscopic stigmata (visible vessel, adherent clot, and oozing) were useful in identifying those at increased risk of rebleeding but not as an indication for surgery. Six patients underwent surgery for peptic ulceration with one postoperative death. There were four deaths among the other patient groups giving an overall mortality of 4.6%. This audit shows a low mortality after acute upper GI haemorrhage can be achieved even in an elderly population in a DGH without the establishment of a specialist unit but with an agreed policy of management.
Acute Disease↗
Spontaneous neurodegeneration in transgenic mice with mutant prion protein.
Transgenic mice were created to assess genetic linkage between Gerstmann-Sträussler-Scheinker syndrome and a leucine substitution at codon 102 of the human prion protein gene. Spontaneous neurologic disease with spongiform degeneration and gliosis similar to that in mouse scrapie developed at a mean age of 166 days in 35 mice expressing mouse prion protein with the leucine substitution. Thus, many of the clinical and pathological features of Gerstmann-Sträussler-Scheinker syndrome are reproduced in transgenic mice containing a prion protein with a single amino acid substitution, illustrating that a neurodegenerative process similar to a human disease can be genetically modeled in animals.
Amino Acid Sequence↗
Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication.
Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) prion protein (PrP) genes were used to probe the mechanism of scrapie prion replication. Four Tg lines expressing HaPrP exhibited distinct incubation times ranging from 48 to 277 days, which correlated inversely with HaPrP mRNA and HaPrPC. Bioassays of Tg brain extracts showed that the prion inoculum dictates which prions are synthesized de novo. Tg mice inoculated with Ha prions had approximately 10(9) ID50 units of Ha prions per gram of brain and less than 10 units of Mo prions. Conversely, Tg mice inoculated with Mo prions synthesized Mo prions but not Ha prions. Similarly, Tg mice inoculated with Ha prions exhibited neuropathologic changes characteristic of hamsters with scrapie, while Mo prions produced changes similar to those in non-Tg mice. Our results argue that species specificity of scrapie prions resides in the PrP sequence and prion synthesis is initiated by a species-specific interaction between PrPSc in the inoculum and homologous PrPC.
Animals↗
Mortality in patients with bleeding peptic ulcer.
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England↗
Quenching of the amidolytic activity of one-chain tissue-type plasminogen activator by mutation of lysine-416.
In contrast to most other serine proteases, tissue-type plasminogen activator (t-PA) possesses enzymatic activity as the one-chain zymogen form. The hypothesis that lysine residues 277 or 416 may be involved in stabilization of an active conformation of one-chain t-PA via salt-bridge formation with aspartic acid residue 477 was tested by site-directed mutagenesis. Four recombinant t-PA mutants were constructed. The amidolytic activities of these analogues were compared to that of authentic t-PA. Substitution of arginine-275 provided an analogue [( R275G]t-PA) resistant to plasmin cleavage. The amidolytic activity of [R275G]t-PA was comparable to that of authentic one-chain t-PA, and so was the activity of [R275L,K277L]t-PA, in which additional substitution of lysine residue 277 was carried out. This suggested that its presence was nonessential for obtaining one-chain t-PA activity. In contrast, substitution of lysine residue 416 to obtain [K416S]t-PA and [K416S,H417T]t-PA resulted in substantial quenching of amidolytic one-chain activity. As expected, the amidolytic activities of the two-chain forms were less affected by the substitution. Involvement of lysine residue 416 in one-chain t-PA activity was also indicated by decreased activities of [K416S]t-PA and [K416S,H417T]t-PA with plasminogen as the substrate. The one-chain activity of the lysine residue 416 substitution analogues was partially restored in the presence of fibrin. This could indicate that strong ligands such as fibrin might provide an alternative stabilization of the active conformation of one-chain t-PA.
Amidohydrolases↗
Regulation of testicular function by insulin and transforming growth factor-beta.
Hyperinsulinism is associated with disorders of androgen production in humans. We have studied the effects of insulin and insulin-like growth factor-1 on androgen production in vitro using a crude preparation of mouse Leydig cells incubated with luteinizing hormone in a serum-free medium. We found a positive correlation between testosterone production and the luteinizing hormone dose over 3 hours. Exposure of the cells for 1 hour to insulin (1 micrograms/ml) prior to the addition of luteinizing hormone significantly augmented the amount of testosterone produced in response to the gonadotropin when added after this preincubation. In contrast, prior exposure of the cells to proinsulin (30 micrograms/ml), insulin-like growth factor-1 (30 ng/ml), or epidermal growth factor-1 (1 micrograms/ml) did not influence the testosterone response to luteinizing hormone. Transforming growth factor-beta reduced the testosterone response to luteinizing hormone. Transforming growth factor-beta (1,000 pg/ml) blocked the insulin augmentation of luteinizing hormone-stimulated testosterone production. We conclude that insulin has an endocrine effect on testosterone production by mouse Leydig cells in vitro. Furthermore, the Leydig cell response to insulin is itself sensitive to interaction with transforming growth factor-beta which may operate as part of the paracrine control of Leydig cell function.
Aging↗
Effect of training frequency and specificity on isometric lumbar extension strength.
To investigate the effects of training frequency and specificity of training on isolated lumbar extension strength, 72 men (age = 31 +/- 9 years) and 42 women (age = 28 +/- 9 years) were tested before and after 12 weeks of training. Each test involved the measurement of maximum voluntary isometric torque at 72 degrees, 60 degrees, 48 degrees, 36 degrees, 24 degrees, 12 degrees, and 0 degrees of lumbar flexion. After the pretraining tests, subjects were randomly stratified to groups that trained with variable resistance dynamic exercise every other week (1X/2 weeks, n = 19), once per week (1X/week, n = 22), twice per week (2X/week, n = 23) or three times per week (3X/week, n = 21); a group that trained isometrically once per week (n = 14); or a control group that did not train (n = 15). Analysis of covariance showed that all training groups improved their ability to generate isometric torque at each angle measured when compared with controls (P less than 0.05). There was no statistical difference in adjusted posttraining isometric torques among the groups that trained (P greater than 0.05), but dynamic training weight increased to a lesser extent (P less than 0.08) for the 1X/2 weeks group (26.6%) than for the groups that trained 1X/week, 2X/week, and 3X/week (37.2 to 41.4%). These data indicate that a training frequency as low as 1X/week provides an effective training stimulus for the development of lumbar extension strength. Improvements in strength noted after isometric training suggest that isometric exercise provides an effective alternative for developing lumbar strength.
Adult↗
Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques.
Three transgenic mouse lines designated Tg 69, 71, and 81 were produced harboring a Syrian hamster (Ha) prion protein (PrP) gene; all expressed the cellular HaPrP isoform in their brains. Inoculation of Tg 81 mice or hamsters with Ha prions caused scrapie in integral of 75 days; nontransgenic control mice failed to develop scrapie after greater than 500 days. Tg 71 mice inoculated with Ha prions developed scrapie in integral of 170 days. Both Tg 71 and Tg 81 mice exhibited spongiform degeneration and reactive astrocytic gliosis, and they produced the scrapie HaPrP isoform in their brains. Tg 81 brains also showed HaPrP amyloid plaques characteristic of Ha scrapie and contained integral of 10(9) ID50 units of Ha prions based on Ha bioassays. Our findings argue that the PrP gene modulates scrapie susceptibility, incubation times, and neuropathology; furthermore, they demonstrate synthesis of infectious scrapie prions programmed by a recombinant DNA molecule.
Amyloid↗
Back injuries to fast bowlers in cricket: a prospective study.
Eighty-two high performance young male fast bowlers (mean age 16.8 years) were tested immediately prior to the season for selected kinanthropometric and physiological data. Subjects were also filmed both laterally (200 Hz) and from above (100 Hz) while bowling so that their front foot impacted a force platform during the delivery stride. The players then completed a log book over the ensuing season that detailed their training and playing programmes. All cricket related injuries over this season were assessed by a sports physician who used computerized tomography to assist in the diagnosis of spinal injuries. At the completion of this season the players were grouped according to their injury status (Group 1--bony injury to a vertebra; Group 2--soft tissue injury to the back that caused the player to miss at least one game, and Group 3--no injuries). A one-way analysis of variance was used to identify if any variables were significantly (P less than 0.05) different between the three groups, and a Scheffe post hoc comparison was used to determine which groups were significantly different. Eleven per cent of the players sustained a stress fracture to a vertebra(e) (L4 to S1), while 27 per cent sustained a soft tissue injury to the back. Bowlers with a low longitudinal foot arch were more likely to develop a stress fracture than those with a high arch. Shoulder depression and horizontal flexion strength for the preferred limb and quadriceps power in the non-preferred limb were also significantly related to back injuries. Results suggest that bowlers with the above physical characteristics, who bowl with these biomechanical techniques for extended periods, are predisposed to back injuries.
Adolescent↗
Phorbol ester and calcium ionophore are sufficient to promote cell replication in cultures of quiescent human B lymphocytes.
Highly purified, resting B cells could be induced to grow for up to 10 days by culturing in the presence of a synergistic combination of a tumour-promoting phorbol ester and the calcium ionophore ionomycin. In spite of evident cell death occurring, four to five times as many viable B lymphocytes could be harvested at the end of culture than were initially plated. Soluble factors derived from T cells (interleukin-2, commercial B-cell growth factor) or monocytes (interleukin-1) failed to augment further the growth-promotion observed. Evidence is presented to suggest that an autocrine component might be necessary for maintenance of the cell-cycle and growth initiated by the phorbol ester and calcium ionophore combination. The significance of these findings to B-cell physiology are discussed.
B-Lymphocytes↗