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Biomedical subjects

C Ferguson

Publications and source records attributed to C Ferguson.

At least 55 records · Page 3Linked to original sources

Cytoskeletal proteins of insect muscle: location of zeelins in Lethocerus flight and leg muscle.

Asynchronous insect flight muscles produce oscillatory contractions and can contract at high frequency because they are activated by stretch as well as by Ca2+. Stretch activation depends on the high stiffness of the fibres and the regular structure of the filament lattice. Cytoskeletal proteins may be important in stabilising the lattice. Two proteins, zeelin 1 (35 kDa) and zeelin 2 (23 kDa), have been isolated from the cytoskeletal fraction of Lethocerus flight muscle. Both zeelins have multiple isoforms of the same molecular mass and different charge. Zeelin 1 forms micelles and zeelin 2 forms filaments when renatured in low ionic strength solutions. Filaments of zeelin 2 are ribbons 10 nm wide and 3 nm thick. The position of zeelins in fibres from Lethocerus flight and leg muscle was determined by immunofluorescence and immunoelectron microscopy. Zeelin 1 is found in flight and leg fibres and zeelin 2 only in flight fibres. In flight myofibrils, both zeelins are in discrete regions of the A-band in each half sarcomere. Zeelin 1 is across the whole A-band in leg myofibrils. Zeelins are not in the Z-disc, as was thought previously, but migrate to the Z-disc in glycerinated fibres. Zeelins are associated with thick filaments and analysis of oblique sections showed that zeelin 1 is closer to the filament shaft than zeelin 2. The antibody labelling pattern is consistent with zeelin molecules associated with myosin near the end of the rod region. Alternatively, the position of zeelins may be determined by other A-band proteins. There are about 2.0 to 2.5 moles of myosin per mole of each zeelin. The function of these cytoskeletal proteins may be to maintain the ordered structure of the thick filament.

Animals↗

Out-of-hours workload of junior and senior house surgeons in a district general hospital.

The objective of this study was to assess the out-of-hours workload of junior and senior house officers in general surgery working in a busy DGH in relation to the 'New Deal' guidelines on junior doctors' hours of work. We also wanted to identify safe levels of manning for these grades of staff and to collect accurate data on workload upon which decisions could be made regarding any change in manning levels consequent upon the 'New Deal'. The study is a prospective audit of all work undertaken by 11 junior and senior house surgeons attached to six consultants between 1700 hrs and 0800 hrs during a 16-day period in August 1992. The results showed that the out-of-hours workload of the five JHOs and six SHOs proved to be very onerous. The rotas were 1:5 or 1:6 for emergencies depending on grade plus 1:11 for ward cover. The JHOs were occupied for 70 per cent of the period between 1700 hrs and 2400 hrs and 32.5 per cent of the period after 2400 hrs. For the same periods the SHOs were busy for 61 per cent and 29 per cent respectively. The doctors covering ward duties were occupied for 48 per cent of the period up to midnight when the duty period ended. Both grades got four hours sleep on five of 16 nights. Non-medical tasks accounted for 29 per cent of the ward doctors working time but were a small part of the other doctors work. It was concluded that in this typical busy DGH junior and senior house officers work extremely hard when on call, and that they cannot be reasonably be asked to further increase their level of activity. It follows that a reduction in the hours of work will require additional staff if the standard of care delivered to the patients is to be maintained.

Hospitals, District↗

Kettin, a large modular protein in the Z-disc of insect muscles.

Z-discs of insect flight muscle contain a large protein of 500-700 kDa. Monoclonal antibodies label an epitope in the molecule at the Z-disc in Drosophila and Lethocerus (waterbug). A partial cDNA of 1.6 kb from the Drosophila gene has been cloned and sequenced. The corresponding amino acid sequence has a modular structure composed of four conserved repeats of 95 amino acids homologous to immunoglobulin C2 domains (called class II domains in muscle proteins), separated by less conserved linker sequences of 35 amino acids. An expressed class II domain with flanking linker sequences binds to actin and alpha-actinin but not to myosin. Single molecules of the protein would be large enough to span the Z-disc. We suggest that the protein acts as scaffolding in the Z-disc and we call the protein kettin. The Ca2+ activated protease, calpain, disrupts the Z-disc of striated muscle, releasing alpha-actinin intact. Calpain digests kettin to a series of peptides of between 30 and 170 kDa which are released from the myofibril. Digestion of kettin may cause disintegration of the Z-disc and alpha-actinin release which lead to disassembly of the myofibril.

Amino Acid Sequence↗

Bedside measurement of intra-abdominal pressure (IAP) via an indwelling naso-gastric tube: clinical validation of the technique.

OBJECTIVES: To compare measurements of intraabdominal pressure (IAP) via a naso-gastric tube with the previously validated technique of IAP measurement via a urinary bladder catheter. To examine an association between elevated IAP and oliguric acute renal failure. DESIGN: Simultaneous paired measurements of gastric and urinary bladder pressures in supine patients. SETTING: The general intensive care units of two London hospitals. PATIENTS: 141 Paired measurements of intragastric and urinary bladder pressures were obtained in 26 general intensive care patients. MEASUREMENTS AND RESULTS: With the patient lying supine, 50 ml of sterile water were instilled via manometer tubing into the stomach and bladder following drainage of each viscera. The mid-axillary line was used as the zero reference, and cavity pressures noted in centimeters of water (cmH2O) at end expiration. The results were compared using the technique of Bland and Altman. RESULTS: Gastric pressure may be approximately 2.5 cmH2O above or below urinary bladder pressure. Manometric measurement of the gastric pressure via a naso-gastric tube provides a simple, reliable, non-invasive technique of IAP measurement. IAP should be regularly monitored in patients with abdominal distension at risk of acute renal failure.

Acute Kidney Injury↗

Factors associated with successful laparoscopic cholecystectomy for acute cholecystitis.

OBJECTIVE: This article determined which preoperative data correlated with successful completion of a laparoscopic cholecystectomy in patients with acute cholecystitis. SUMMARY BACKGROUND DATA: Although laparoscopic cholecystectomy is the procedure of choice in chronic cholecystitis, its use in acute cholecystitis may be associated with higher costs and complication rates. It is not known which patients with acute cholecystitis are likely to require conversion to open cholecystectomy based on preoperative data or if a cooling-off period with medical therapy can diminish inflammation and increase the chance of successful laparoscopic cholecystectomy. METHODS: All laparoscopic cholecystectomies done by the authors between 10/90 and 2/92 were reviewed. Data on cases of acute cholecystitis were prospectively collected on standardized data forms. RESULTS: Twenty of 281 laparoscopic cholecystectomies were done for acute cholecystitis; 7/20 patients with acute cholecystitis required conversion to open cholecystectomy compared with 6/281 patients undergoing elective operation for chronic cholecystitis. In patients with acute cholecystitis the interval from admission to cholecystectomy in the successful cases was 0.6 days vs. 5 days in the cases requiring conversion to open cholecystectomy (p = .01). Cases requiring conversion to open cholecystectomy also had higher WBC (14.0 vs. 9.0, p < .05), alkaline phosphatase (206 vs. 81, p < .02, and APACHE II scores (10.6 vs. 5.1, p < .05). Ultrasonographic findings such as gallbladder distention, wall thickness, and pericholecystic fluid did not correlate with the success of laparoscopic cholecystectomy. Patients converted from laparoscopic to open cholecystectomy required more operating room time (120 min vs. 87 min, p < .01) and more postop hospital days (6 vs. 2, p < .001). CONCLUSIONS: Laparoscopic cholecystectomy for acute cholecystitis should be done immediately after the diagnosis is established because delaying surgery allows inflammation to become more intense, thus increasing the technical difficulty of laparoscopic cholecystectomy.

Acute Disease↗

Exertional heat stroke induced by amphetamine analogues. Does dantrolene have a place?

There are increasing numbers of patients admitted to hospital as a result of ingesting amphetamine-like drugs. The most severe cases exhibit hyperthermia, rhabdomyolysis, coagulopathy and renal failure. We describe six such patients with varying severity of intoxication, and have reviewed the recent literature with particular reference to the use of dantrolene. One of our patients died but the others all survived. There is little evidence that dantrolene influenced the outcome in patients reported to date. We believe that a controlled trial should be carried out in amphetamine-related hyperthermia before the use of dantrolene becomes widespread.

3,4-Methylenedioxyamphetamine↗

The substitution of glycine 661 by arginine in type III collagen produces mutant molecules with different thermal stabilities and causes Ehlers-Danlos syndrome type IV.

Previous studies have shown that Ehlers-Danlos syndrome type IV (EDS IV) is caused by mutations of type III collagen (COL3A1). Here we have characterised the most amino-terminal glycine substitution so far described in a patient with EDS IV. A combination of peptide mapping and chemical cleavage analysis of cDNA localised the mutation in cyanogen bromide peptide CB5. Sequence analysis showed a G to A mutation, converting glycine 661 to arginine, which was a new dominant mutation. Analysis of type III collagen secreted by cultured fibroblasts showed an overmodified mutant protein with normal thermal stability. However, the intracellularly retained form melted 2 degrees C lower than normal. This indicated that molecules resulting from the same mutation can differ in their thermal stabilities.

Arginine↗

Staurosporine, a protein kinase C inhibitor, decreases the general anesthetic requirement in Rana pipiens tadpoles.

Protein kinase C, the intracellular effector for the inositol phosphate-mediated signal transduction pathway, plays a key role in neurotransmission in the central nervous system. Although the in vitro activity of protein kinase C is inhibited by therapeutic concentrations of volatile anesthetics, the relation of this effect to in vivo obtundation has not been established. If obtundation by volatile anesthetics involves protein kinase C inhibition, then an inhibitor of this enzyme should decrease the anesthetic requirement. To test this hypothesis, we compared the EC50S of halothane and diethylether for loss of the righting reflex in Rana pipiens tadpoles pretreated with staurosporine and in untreated controls. Anesthetic concentrations were confirmed by gas chromatography and staurosporine concentrations by ultraviolet absorbance spectrophotometry. Results obtained in more than 1000 animals indicated that pretreatment with staurosporine concentrations in the nanomolar range significantly decreased the EC50 for both halothane (68% of control; P < 0.035) and diethylether (41% of control; P < 0.001). This finding implies that protein kinase C inhibition may play a role in general anesthetic-induced obtundation.

Alkaloids↗

[Opinions of Honduran adults about street children].

The purpose of this study was to determine the beliefs parents of working children and business people have about two types of street children, those who work on the street and those who are abandoned and live on the street. In 1991 forty-nine parents of working children and 49 business people from Tegucigalpa were administered a questionnaire listing 36 beliefs about the lifestyles of abandoned and working children and causes of children adopting these ways of life. Among parents of working children, education was significantly lower and mothers were more likely to be single women than in the business people sample. There were many beliefs about the lifestyles of street children on which both groups agreed, but parents of working children held the youngsters more accountable for choosing to work or live in the street. Parents also seemed to be more aware of the health risks to both types of street children than business people who felt working children were at less risk than abandoned children. Business people perceived abandoned children to be victims of single parenthood and solvent abuse. A deeper exploration of the views held by families of street children may assist those seeking to help them.

Adult↗

Functional expression of plant plasma membrane H(+)-ATPase in yeast endoplasmic reticulum.

Recombinant plant plasma membrane H(+)-ATPase has been produced in a yeast expression system comprising a multicopy plasmid and the strong promoter of the yeast PMA1 gene. Western blotting with a specific monoclonal antibody showed that the plant ATPase is one of the major membrane proteins made by the transformed cells, accounting for about 1% of total yeast protein. The plant ATPase synthesized in yeast is fully active. It hydrolyzes ATP, pumps protons, and the reaction cycle involves a phosphorylated intermediate. Phosphorylation is possible from both ATP and Pi. Unlike the situation in plants, however, most of the plant ATPase is not expressed in the yeast plasma membrane. Rather, the enzyme appears to remain trapped at a very early stage of secretory pathway: insertion into the endoplasmic reticulum. This organelle was observed to proliferate in the form of stacked membranes surrounding the yeast nucleus in order to accommodate the large amount of plant ATPase produced. In this location, the plant ATPase can be purified with high yield (70 mg from 1 kg of yeast) from membranes devoid of endogenous yeast plasma membrane H(+)-ATPase. This convenient expression system could be useful for other eukaryotic membrane proteins and ATPases.

Adenosine Triphosphate↗