Tomlinson and the BMA.
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Health Facility Closure↗
Biomedical subjects
J Thompson
Publications and source records attributed to J Thompson.
Toxicity of Bordetella avium beta-cystathionase toward MC3T3-E1 osteogenic cells.
Bordetella avium is the etiological agent of an upper respiratory disease in birds which, symptomatically and pathologically, resembles bordetellosis in humans. Studies of the virulence of this organism revealed a novel cytotoxic protein, designated osteotoxin, that was lethal for MC3T3-E1 osteogenic cells, fetal bovine trabecular cells, UMR106-01(BSP) rat osteosarcoma cells, and embryonic bovine tracheal cells. The osteotoxin lacked dermonecrotic toxin activity, exhibited no cross-reactivity with antibody against B. avium dermonecrotic toxin, and was non-proteolytic. Osteotoxin (M(r) approximately 80,000 by gel filtration, pI 5.4) was purified to electrophoretic homogeneity from B. avium 197. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and spectrophotometric analyses showed that the native protein was a homodimer and that each of the non-covalently linked subunits (M(r) approximately 41,000) contained one molecule of pyridoxal 5'-phosphate. Microsequencing of the first 32 amino acids from the NH2 terminus allowed the synthesis of two oligonucleotide probes, which, together with polyclonal antibody to the purified protein, facilitated cloning, sequencing, and expression of the osteotoxin gene product in Escherichia coli. The open reading frame encodes a polypeptide of 396 amino acid residues (M(r) = 42,606, calculated pI 5.9), whose sequence exhibits approximately 38% identity (approximately 60% similarity) to pyridoxal 5'-phosphate-dependent beta-cystathionase(s) from E. coli, Salmonella typhimurium, and rat liver. The characteristic motif, TKYXXGHSD, associated with binding the cofactor in these enzymes is also present in osteotoxin. Physicochemical and enzymatic analyses established the coidentity of osteotoxin with beta-cystathionase. The region upstream of the beta-cystathionase (metC) gene in B. avium 197 lacked regulatory sequences ("Met boxes") described for metC in enteric species, and enzyme production was not repressed by methionine. Incubation of MC3T3-E1 osteogenic cells in medium containing L-[35S]cystine and purified beta-cystathionase resulted in 35S-labeling of the enzyme and at least one major MC3T3-E1 cell protein (M(r) approximately 50,000). cytotoxicity can be attributed to: 1) beta-cystathionase-catalyzed cleavage of L-cystine in the medium and formation of reactive sulfane-containing derivative(s), and 2) transfer of sulfane sulfur to metabolically sensitive or structurally important proteins in the osteogenic cells.
Amino Acid Sequence↗
Prophylaxis for endocarditis.
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Endocarditis, Bacterial↗
Inhaled nitric oxide in chronic obstructive lung disease.
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Acetylcholine↗
Spatiotemporal expression of pregnancy-specific glycoprotein gene rnCGM1 in rat placenta.
As a basis towards a better understanding of the role of the pregnancy-specific glycoprotein (PSG) family in the maintenance of pregnancy, detailed investigations are described on the expression of a recently identified rat PSG gene (rnCGM1) at the mRNA and protein levels. Using specific oligonucleotide primers, rnCGM1 transcripts were identified after reverse transcription, polymerase chain reaction, and hybridization with a radiolabelled, internal oligonucleotide. Transcripts were only found in significant amounts in placenta. In situ hybridization visualized rnCGM1 transcripts at day 14 post coitum (p.c.), in secondary trophoblast giant cells and in the spongiotrophoblast. Only those secondary giant cells lining the maternal decidua were positive. In contrast, primary giant cells did not contain rnCGM1 mRNA. At day 18 p.c., rnCGM1 transcripts were almost exclusively detectable in the spongiotrophoblast. No rnCGM1 transcripts were found in rat embryos of these two developmental stages. Rabbit antisera were generated against the amino-terminal immunoglobulin variable-like domain and against a synthetic peptide containing the last 13 carboxy-terminal amino acids of rnCGM1. Both antisera recognized a 124 kDa protein in day 18 rat placental extracts as identified by Western blot analysis. The anti-peptide antiserum recognized a 116 kDa protein in the serum of a 14 day p.c. pregnant rat that is absent from the sera of non-pregnant females. Taken together, these results confirm exclusive expression of rnCGM1 in the rat trophoblast, but unlike human PSG, negligible or no expression is found in other organs, such as fetal liver or salivary glands, indicating a more specialized function of rnCGM1. Its spatiotemporal expression pattern is conducive with a potential role of PSG in protecting the fetus against the maternal immune system and/or in regulating the invasive growth of trophoblast cells.
Amino Acid Sequence↗
Replacement of the L11 binding region within E.coli 23S ribosomal RNA with its homologue from yeast: in vivo and in vitro analysis of hybrid ribosomes altered in the GTPase centre.
Replacement of the protein L11 binding domain within Escherichia coli 23S ribosomal RNA (rRNA) by the equivalent region from yeast 26S rRNA appeared to have no effect on the growth rate of E.coli cells harbouring a plasmid carrying the mutated rrnB operon. The hybrid rRNA was correctly processed and assembled into ribosomes, which accumulated normally in polyribosomes. Of the total ribosomal population, < 25% contained wild-type, chromosomally encoded rRNA; the remainder were mutant. The hybrid ribosomes supported GTP hydrolysis dependent upon E.coli elongation factor G, although at a somewhat reduced rate compared with wild-type particles, and were sensitive to the antibiotic, thiostrepton, a potent inhibitor of ribosomal GTPase activity that binds to 23S rRNA within the L11 binding domain. That thiostrepton could indeed bind to the mutant ribosomes, although at a reduced level relative to that seen with wild-type ribosomes, was confirmed in a non-equilibrium assay. The rationale for the ability of the hybrid ribosomes to bind the antibiotic, given that yeast ribosomes do not, was provided when yeast rRNA was shown by equilibrium dialysis to bind thiostrepton only 10-fold less tightly than did E.coli rRNA. The extreme conservation of secondary, but not primary, structure in this region between E.coli and yeast rRNAs allows the hybrid ribosomes to function competently in protein synthesis and also preserves the interaction with thiostrepton.
Base Sequence↗
Role of glucocorticosteroids in the treatment of infectious diseases.
The role of glucocorticosteroids in the management of infectious diseases in man remains controversial, although experimental data obtained both in in vitro systems and in experimental infections in animals provide evidence of a beneficial effect of such treatment. Their use in the treatment of Pneumocystis carinii pneumoniae and severe typhoid fever seems indicated. A beneficial effect on the treatment of bacterial meningitis needs to be confirmed. Sufficient data are now available that argue against steroid treatment in septic shock. However, new treatment modalities such as monoclonal antibodies against endotoxin and inflammatory mediators are currently being developed to modulate infectious inflammation. This could also bring a renaissance of the role of glucocorticosteroids in the treatment of infectious diseases.
Animals↗
Invasive pressure monitoring of patients during magnetic resonance imaging.
The purpose of this paper is to describe a system for monitoring patients who require general anaesthesia, profound sedation or intensive care while undergoing high field (> or = 1.5 T) magnetic resonance (MR) imaging. Continuous evaluation of invasive and noninvasive pressures, inspired and end-tidal respiratory gas concentrations, body temperature, heart rate, ECG and pulse oximetry were measured successfully during the MR examination. Diagnostic quality MR images were acquired on all 15 monitored patients. The calculated signal-to-noise ratios were not different between the control and monitored patients. Commonly encountered technical problems and their solutions are described. This study demonstrates that invasive monitoring can be safely performed in critically ill patients who are undergoing high field MR examinations.
Adult↗
The PH domain: a common piece in the structural patchwork of signalling proteins.
The 'pleckstrin homology' domain is an approximately 100-residue protein module that has recently been added to the domain catalogue of signalling proteins. For this review we have made an extensive database search using a profile search method, and found a number of additional proteins that may contain PH domains. The PH domain is present in many kinases, isoforms of phospholipase C, GTPases, GTPase-activating proteins and nucleotide-exchange factors, including such proteins as Vav, Dbl and Bcr, and there are two PH domains in a guanine-nucleotide releasing factor of Ras. Many PH-domain-containing proteins interact with GTP-binding proteins. We have also identified a PH domain in beta-adrenergic receptor kinase exactly in the region that has already been shown to be involved in binding to the beta and gamma subunits of a heterotrimeric G protein. This suggests that PH domains may be involved in interactions with GTP-binding proteins.
Amino Acid Sequence↗
Isolated limb perfusion with urokinase for acute ischemia.
PURPOSE: Isolated limb perfusion with urokinase was used to salvage an acutely ischemic lower limb. METHODS: Isolated limb perfusion with urokinase over a 90-minute period was used in the treatment of a 69-year-old female patient with acute ischemia of the left leg after thrombosis of a femoral artery bypass graft. Previous balloon embolectomy and heparin therapy had failed. The flow rate was able to be increased progressively without rise in the line pressure during the course of the perfusion, indicating an increase in capacity of the peripheral arterial bed. Fibrinogen and plasminogen levels in the isolated circulation remained low throughout the perfusion. The concentration of cross-linked fibrin degradation particles (d. dimer) rose progressively in the isolated circulation but remained at normal levels in the systemic circulation during perfusion. RESULTS: Completion angiography demonstrated clearance of thrombus in the popliteal artery and appearance of arteries not seen on preperfusion films. Clinical improvement paralleled the angiographic appearances, with restoration of limb viability. CONCLUSION: We concluded that isolated limb perfusion with use of urokinase is safe and worthy of further investigation.
Acute Disease↗
Malignant catarrhal fever in a swamp buffalo (Bubalus bubalis) calf in New Zealand.
Malignant catarrhal fever was diagnosed in a newly imported swamp buffalo calf. This disease is prevalent in deer and cattle in New Zealand and causes sporadic losses in these species. The disease is recognised as a problem in buffaloes overseas and this paper records the first case in a swamp buffalo in New Zealand.
Journal Article↗
Sequential administration of two human-rhesus rotavirus reassortant strains of VP7 serotype 1 and 2 specificity to infants and young children.
Rotavirus vaccine strains representing serotypes 1 and 2 have been derived by reassortment between genes of a rhesus rotavirus master strain, MMU18006, and the gene from human viruses coding for VP7, a surface protein with neutralizing determinants. As simultaneous administration of these two human rotavirus reassortants had resulted in disappointing strain-specific immunity, these two vaccines were administered sequentially to infants and young children to assess whether immunity to both serotypes could be achieved with two monovalent doses. Following initial immunization with RRVxDS-1, a serotype 2 vaccine, 12 of 13 shed virus and showed serologic responses to multiple rotavirus proteins. However, with subsequent administration of RRVxD, serotype 1, only 2 of 12 shed virus, and an enhancement or broadening of the immune response was not uniformly seen. Although rhesus rotavirus vaccines are immunogenic with primary administration of monovalent vaccine in seronegative children, and supplemental seroresponses are seen with a second dose, other strategies or new vaccine candidates must be sought to induce immunity against the multiple serotypes of human rotavirus.
Administration, Oral↗
Comparison of monovalent and trivalent live attenuated influenza vaccines in young children.
Fifty children, 6 months to 2 years of age, were vaccinated intranasally with a trivalent preparation containing 10(6) TCID50 each of H1N1 and H3N2 and 10(4) (n = 14) or 10(6) (n = 36) TCID50 of B live, attenuated, cold-adapted (ca) influenza strains. The same doses were administered as monovalent vaccines to 69 comparably aged children. Forty-five controls were given placebo. No clinically significant adverse reactions to vaccines were observed. Of children seronegative to H1N1 or H3N2, > or = 90% were infected by these vaccine strains. Trivalent vaccine containing 10(4) TCID50 of B infected only 27% of children seronegative to B (3/11), which was markedly reduced from the 88% infection rate (7/8) following monovalent B vaccine of the same dose (P = .02); increasing the B dose to 10(6) TCID50 increased the infection rate to 81% (21/26). Replication of ca influenza viruses in tissue culture matched vaccine responses. Trivalent ca influenza vaccines can be formulated that are safe and immunogenic in young children.
Animals↗
A comparison of the mechanogram of the ankle jerk in men and women: observations using an adjustable dorsiflexing torque, high inertia mechanical filter and automatic readout system.
An instrument of new design has been constructed to measure the contractions of the calf musculature resulting from a tap on the Achilles tendon. The instrument provides a predetermined and adjustable dorsiflexing torque from a printed motor, but the contractions are virtually isometric as the system is one of high inertia. Peak force, half-contraction time and half-relaxation time are monitored by electronic circuits equipped with digital output meters. Observations have been made on fifty-two male and forty-five female medical students. There were no significant differences in the peak torques generated by the contractions between the men and women students and no difference in the half-contraction times. The half-relaxation times of the women were, however, significantly longer than those of the men (P = 0.0001). In another group of students the EMG discharges following a tendon tap were recorded, there was no significant difference in the duration of the activity in men and women. Observations have also been made on twenty-three male and seventy female subjects whose mean ages were in the mid-sixties. The peak torques generated by the contractions were significantly higher in the women (P = 0.03). There was no difference in the half-contraction times, but the half-relaxation times of the women were significantly longer (P = 0.001). Possible reasons for the differences are discussed.
Adolescent↗
Diet and exercise strategies of a world-class bodybuilder.
This study presents the diet and exercise strategies of a world-class body-builder during an 8-week precompetition period. Weighed food records were kept daily, and body fat, resting metabolic rate (RMR), VO2max, blood lipids, and liver enzymes were measured. Two hrs of aerobic exercise and 3 hrs of weight training were done daily 6 days/week. Mean energy intake was 4,952 kcal/day (54 kcal/kg) and included 1,278 kcal/day from medium-chain triglycerides (MCT). Diet without MCT provided 76% of energy from carbohydrate, 19% from protein (1.9 g protein/kg), and 5% from fat. Micro-nutrients were consumed at > or = 100% of the RDA, except for zinc and calcium, without supplementation. Mean RMR was 2,098 kcal/day and represented 43% of energy intake. VO2max was 53 ml.kg-1.min-1. Underwater weighing showed that body fat decreased from 9% to 7%. Blood lipids were normal, but two liver enzymes were elevated (alanine and aspartate aminotransferase). This world-class bodybuilder achieved body fat goals by following a nutrient dense, high energy, high carbohydrate diet and an exercise program that emphasized both aerobic and anaerobic metabolism.
Adipose Tissue↗
Resting metabolic rate and thermic effect of a meal in low- and adequate-energy intake male endurance athletes.
The resting metabolic rate (RMR) and thermic effect of a meal (TEM) were determined in 13 low-energy intake (LOW) and 11 adequate-energy intake (ADQ) male endurance athletes. The LOW athletes reported eating 1,490 kcal.day-1 less than the ADQ group, while the activity level of both groups was similar. Despite these differences, both groups had a similar fat-free mass (FFM) and had been weight stable for at least 2 years. The RMR was significantly lower (p < 0.05) in the LOW group compared to the values of the ADQ group (1.19 vs. 1.29 kcal.FFM-1.hr-1, respectively); this difference represents a lower resting expenditure of 158 kcal.day-1. No differences were found in TEM between the two groups. These results suggest that a lower RMR is one mechanism that contributes to weight maintenance in a group of low- versus adequate-energy intake male athletes.
Adult↗
Localization and sequence analysis of morphological transforming region III within human cytomegalovirus strain Towne.
A 7.6-kbp BamHI/XbaI EJ subfragment of the Towne XbaI-E fragment of human cytomegalovirus (HCMV) strain Towne has been previously designated as morphological transforming region III (mtrIII) because it induced focal and tumorigenic transformation of rodent fibroblasts. However, in two separate cell systems, mtrIII sequences were not retained because they were not detected in either the focal, tumor or tumor-derived cell lines. In this report, mtrIII was localized to a 2.1-kbp SalI/XbaI DNA fragment. The sequence of the 2,085-bp region was determined and compared to the colinear DNA from HCMV strain AD169. DNA sequence analysis revealed the presence of five open reading frames in Towne mtrIII, two of which are conserved in strain AD169. The localization and sequence analysis of mtrIII will allow further investigation as to the mechanism(s) by which HCMV may play a role in human cancer.
Base Sequence↗
Cyclosporine therapy after cardiac transplantation causes hypertension and renal vasoconstriction without sympathetic activation.
BACKGROUND: Hypertension frequently complicates the use of cyclosporine A (CyA) therapy, and it has been suggested that sympathoexcitation may be the underlying mechanism in this form of hypertension. METHODS AND RESULTS: To further investigate the possibility of a neurogenic mechanism for this hypertensive effect, we studied the effects of CyA on renal blood flow (n = 11), forearm blood flow (n = 8), and sympathetic nervous system activity, assessed by renal and whole-body radiolabeled norepinephrine plasma kinetics and muscle sympathetic nerve firing (using microneurography) in cardiac transplant recipients receiving CyA and a reference group of healthy age-matched control subjects (n = 17). In 11 cardiac transplant patients (2 hours after cyclosporine dose), renal blood flow was significantly lower than that in 8 control subjects (680 +/- 88 vs 1285 +/- 58 mL/min, P < .001). In 5 of these transplant patients, renal blood flow was measured before and for 2 hours after oral cyclosporine and fell progressively over this period, by 37% (P < .01). Total body and renal norepinephrine spillover rates in transplant patients were similar to those in control subjects (3070 +/- 538 vs 2618 +/- 313 pmol/min and 579 +/- 124 vs 573 +/- 95 pmol/min, respectively), and there was no progressive effect in the 2 hours after cyclosporine dosing. Forearm blood flow was increased 2 hours after CyA administration (1.74 +/- 0.31 to 3.12 +/- 0.50 mL x 100 mL-1 x min-1, P < .001), whereas mean arterial blood pressure and noninvasively determined cardiac output (indirect Fick method) were unchanged. Muscle sympathetic nerve discharge rates recorded in 6 of these transplant patients were not different from those in 9 healthy control subjects (37.9 +/- 10.1 vs 41.3 +/- 2.3 bursts per 100 beats per minute). During 90 to 120 minutes of recording after cyclosporine dosing, nerve firing rates remained unchanged. CONCLUSIONS: CyA therapy causes acute renal vasoconstriction without accompanying systemic hemodynamic effects. These renal effects are nonneural, not being attributable to sympathoexcitation.
Cyclosporine↗