Search PubMed⌕ Search

Biomedical subjects

C J Thompson

Publications and source records attributed to C J Thompson.

At least 127 records · Page 7Linked to original sources

The effects of collimation on PET image noise due to scatter, random counts, and deadtime.

The rates for true coincident events, scattered events, and singles in a Positron Emission Tomograph (PET) depend on the collimator size and shape. Monte Carlo techniques were used to compare efficiencies for wanted and unwanted events in multislice PET (MS-PET) and open collimator positron volumetric imaging (PVI) configurations. All systems used cylindrical arrays of bismuth germanate (BGO) or NaI crystals 51 cm in diameter and 10 cm deep suitable for whole brain imaging. The PVI systems detect about five times more true coincident events at low activity concentrations, but their scatter fraction is about three times higher. They are also much more sensitive to activity outside the scan field. As well as causing random counts when they fell within the energy acceptance window, single events are the main cause of deadtime. When the detectors are made from light-encoded blocks deadtime is the major limitation at high count rates. When discrete crystals are used, the efficiency is lower and the random count rates are a more significant source of noise. Noise-effective count rates are used to compare the relative cost in system performance among different systems and sources of noise.

Brain↗

Osmotic and non-osmotic regulation of thirst and vasopressin secretion in patients with compulsive water drinking.

OBJECTIVE: To examine the osmotic and non-osmotic regulation of thirst and AVP release in patients with compulsive water drinking. DESIGN: A 2-hour intravenous infusion of hypertonic (855 mmol/l) sodium chloride solution, followed by a 2-hour drinking period. PATIENTS: Seven patients with compulsive water drinking, seven patients with diabetes insipidus and seven healthy controls. MEASUREMENTS: Plasma AVP, osmolality, sodium and haematocrit, thirst ratings on a visual analogue scale and the volume of water drunk in 2 hours following infusion. RESULTS: Plasma AVP responses to osmotic stimulation, and non-osmotic inhibition by drinking, were normal in patients with compulsive water drinking. Basal thirst ratings were higher in compulsive water drinking than in either diabetes (P less than 0.001) or controls (P less than 0.001), despite lower basal plasma osmolalities. There was a significant rise in thirst ratings during saline infusion, which correlated closely with plasma osmolality, in all three groups, but the final thirst ratings were higher in compulsive water drinkers, who subsequently drank more water than in either diabetes insipidus (P less than 0.01) or controls (P less than 0.001). Drinking rapidly lowered thirst ratings in controls and diabetes insipidus before changes occurred in plasma osmolality, but remained elevated in patients with compulsive water drinking. Linear regression analysis defined a lower osmotic threshold for thirst in compulsive water drinking compared with controls or diabetes insipidus. CONCLUSIONS: There are abnormalities of the osmotic stimulation and non-osmotic inhibition of thirst in compulsive water drinking, suggesting that the underlying defect is one of interpretation of osmotic and non-osmotic inputs. Measurement of thirst responses during hypertonic saline infusion and subsequent water drinking may provide useful diagnostic information in the differentiation of polyuric states.

Adult↗

Site-specific integration of the Streptomyces plasmid pSAM2 in Mycobacterium smegmatis.

A method which allowed the stable integration of DNA fragments at a single site (attB) in the chromosome of Mycobacterium smegmatis was developed using an integrative element from Streptomyces ambofaciens, pSAM2. Vectors containing an Escherichia coli replicon (pBR322), the kanamycin resistance gene from Tn903 for selection in mycobacteria, and a fragment of pSAM2 containing the int gene as well as the attachment site (attP) were constructed and introduced to M. smegmatis by electroporation. Transformants showed stable integration of the plasmid into a single site (attB) of the mycobacterial genome. This approach should be valuable for analyses of gene expression in various mycobacterial species and permit the development of stable recombinant mycobacterial vaccine strains expressing bacterial or viral genes inserted in pSAM2.

Blotting, Southern↗

Nucleotide sequence analysis reveals linked N-acetyl hydrolase, thioesterase, transport, and regulatory genes encoded by the bialaphos biosynthetic gene cluster of Streptomyces hygroscopicus.

Nucleotide sequence analysis of a 5,000-bp region of the bialaphos antibiotic production (bap) gene cluster defined five open reading frames (ORFs) which predicted structural genes in the order bah, ORF1, ORF2, and ORF3 followed by the regulatory gene, brpA (H. Anzai, T. Murakami, S. Imai, A. Satoh, K. Nagaoka, and C.J. Thompson, J. Bacteriol. 169:3482-3488, 1987). The four structural genes were translationally coupled and apparently cotranscribed from an undefined promoter(s) under the positive control of the brpA gene product. S1 mapping experiments indicated that brpA was transcribed by two promoters (brpAp1 and brpAp2) which initiate transcription 150 and 157 bp upstream of brp A within an intergenic region and at least one promoter further upstream within the bap gene cluster (brpAp3). All three transcripts were present at low levels during exponential growth and increased just before the stationary phase. The levels of the brpAp3 band continued to increase at the onset of stationary phase, whereas brpAp1-and brpAp2-protected fragments showed no further change. BrpA contained a possible helix-turn-helix motif at its C terminus which was similar to the C-terminal regulatory motif found in the receiver component of a family of two-component transcriptional activator proteins. This motif was not associated with the N-terminal domain conserved in other members of the family. The structural gene cluster sequenced began with bah, encoding a bialaphos acetylhydrolase which removes the N-acetyl group from bialaphos as one of the final steps in the biosynthetic pathway. The observation that Bah was similar to a rat and to a bacterial (Acinetobacter calcoaceticus) lipase probably reflects the fact that the ester bonds of triglycerides and the amide bond linking acetate to phosphinothricin are similar and hydrolysis is catalyzed by structurally related enzymes. This was followed by two regions encoding ORF1 and ORF2 which were similar to each other (48% nucleotide identity, 31% amino acid identity), as well as to GrsT, a protein encoded by a gene located adjacent to gramicidin S synthetase in Bacillus brevis, and to vertebrate (mallard duck and rat) thioesterases. The amino acid sequence and hydrophobicity profile of ORF3 indicated that it was related to a family of membrane transport proteins. It was strikingly similar to the citrate uptake protein encoded by the transposon Tn3411.

Amidohydrolases↗

A survey of the heat shock response in four Streptomyces species reveals two groEL-like genes and three groEL-like proteins in Streptomyces albus.

A survey of the heat shock response was carried out in a series of streptomycetes. Four major heat shock proteins (HSPs) were observed in each of four species (Streptomyces albus, S. lividans, S. parvulus, S. viridochromogenes) after pulse labeling with [35S]methionine and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three corresponded to the major procaryotic HSPs Lon, DnaK, and GroEL on the basis of their apparent molecular masses (94 to 100, 70, and 56 to 58 kDa, respectively). In addition, a smaller protein (16 to 18 kDa) was detected in all species but was most dramatically induced in S. albus. Consequently, studies focused on this species. As in other procaryotic systems, thermal induction (elicited by a shift from 30 degrees C to 41 degrees C) of the 70- and 94-kDa proteins was transient and expression returned to uninduced levels after 60 min. In contrast, the 56- to 58-kDa (GroEL) and 18-kDa proteins (HSP18) remained induced for more than 2 h. Two-dimensional gel electrophoresis allowed resolution of at least eight S. albus HSPs. HSP56-58 was composed of multiple acidic protein species, whereas HSP18 appeared to be basic. In spite of these differences in their physical characteristics, the N-terminal peptide sequence of HSP18 was similar to those of GroEL-like proteins found in other organisms and identical to one of the HSP56-58 species. In fact, N-terminal amino acid analysis of the S. albus 56- to 58-kDa species showed that it was composed of two proteins that differed in 3 of 10 positions, an observation that was supported by the detection of two groEL-like genes by Southern hybridization. The amino acid sequence of one of these proteins was identical to that of HSP18. Pulse-chase experiments did not reveal evidence of posttranslational processing of either HSP56-58 or HSP18.

Amino Acid Sequence↗

Characterization of the groEL-like genes in Streptomyces albus.

Three GroEL-like heat shock proteins (HSP56, HSP58, and HSP18) have been observed in Streptomyces albus (G. Guglielmi, P. Mazodier, C. J. Thompson, and J. Davies, J. Bacteriol. 173:7374-7381, 1991). Here we report the cloning and complete nucleotide sequence of groEL1, which encodes HSP18 and HSP58, and groEL2, which encodes HSP56. Both nucleotide sequences predicted proteins of 56,680 Da that were 70% identical. The 5' nucleotide sequence of groEL1 coded for a protein corresponding to HSP18 that may be a processed gene product. At least two groEL-like genes were present in all 12 Streptomyces species tested; they were not closely linked in the genome. groEL1, but not groEL2, was adjacent to a groES-like gene.

Amino Acid Sequence↗

Reproducibility of osmotic and nonosmotic tests of vasopressin secretion in men.

We have studied the reproducibility of the thirst and arginine vasopressin (AVP) responses to osmotic and hypoglycemic stimulation in healthy volunteers undergoing repeat hypertonic (855 mmol/l) saline infusion and insulin tolerance tests (ITTs). Hypertonic saline infusion caused similar mean rises in plasma osmolality, AVP, and thirst on each occasion. Linear-regression analysis defined close relationships between the slopes (r = +0.72, P less than 0.05) and the abscissal intercepts (r = +0.89, P less than 0.001) of the regression lines relating plasma osmolality (Posmol) and plasma AVP (PAVP), and the group intraindividual component of the variance for the slopes and intercepts was 7 and 0.6%, respectively. There were close correlations between the slopes (r = +0.79, P less than 0.02) and the intercepts (r = +0.84, P less than 0.01) of the regression lines relating Posmol and thirst, and group intraindividual component of the variance was 14 and 0.7%, respectively. Hypertonic saline infusion was infused on four occasions in four subjects, and the results showed that the linear regression lines relating PAVP and Posmol and thirst and Posmol were reproducible within an individual. There were similar falls in blood glucose and elevations in PAVP in both ITTs. No relationship was defined between the fall in blood glucose and either the rise in PAVP or the area under the AVP curve (AUC). The intraindividual component of the variance for the rise in AVP and the AUC was 77 and 22.5%, respectively. The AVP and thirst responses to osmotic stimulation are highly reproducible, but there is considerable intraindividual variation in the AVP response to hypoglycemia.

Adult↗

Validation of simultaneous PET emission and transmission scans.

A technique for performing simultaneous PET emission and transmission scans is validated in a fluoro-deoxyglucose study. A point source masked into a fan beam of annihilation photons orbits the patient section under study. Coincident events are sorted into two buffers, or rejected, based on the source's position. Both static and dynamic frames of independent and simultaneous studies are compared. The noise effective count rate is reduced to 62% of the value during normal studies. However, the increase in the coefficient of variation in cortical regions is less than 6%. The RMS difference between profile contours through many brain regions is approximately 40% higher comparing two simultaneous emission/transmission scans than when the same analysis is performed on independent emission scans. This difference appears to be due to the noise patterns arising from the use of different transmission scans.

Adult↗

Comparison of thallium-201 and technetium-99m hexakis 2-methoxyisobutyl isonitrile single-photon emission computed tomography for estimating the extent of myocardial ischemia and infarction in coronary artery disease.

Single-photon emission computed tomography (SPECT) using thallium-201 (Tl-201) was compared with technetium-99m hexakis 2-methoxyisobutyl isonitrile (Tc-99m MIBI) in 24 patients with coronary artery diseaes. Patients exercised to the same work load as each isotope was studied. Normal and hypoperfused left ventricular mass was determined with an automated method. Estimated total left ventricular mass was similar for both stress/redistribution Tl-201 and stress/rest Tc-99m MIBI images. The mean estimated defect size in the redistribution Tl-201 images was 32 +/- 34.7 vs 33 +/- 38.4 g in the resting Tc-99m MIBI studies (difference not significant). The individual determinations of defect mass were highly correlated (r = 0.93; p less than 0.0001). Estimated defect size in the stress Tl-201 images (52 +/- 46.2 g) was significantly larger than the exercise Tc-99m MIBI estimates of defect mass (42 +/- 39.9 g; p less than 0.05). A linear correlation existed between stress thallium and technetium estimates of defect size (r = 0.85) but 15 of 24 Tc-99m MIBI defects were smaller than the Tl-201 defects. Partial redistribution of Tc-99m MIBI could explain the discordance. Stress Tc-99m MIBI SPECT defect size determined by visual interpretation or by the use of isocount analysis may be smaller than what is seen with stress Tl-201 SPECT.

Coronary Disease↗

Construction of a series of pSAM2-based integrative vectors for use in actinomycetes.

We have developed vectors which allowed integration of cloned DNA at a single site in the chromosome of Streptomyces lividans 66. These vectors made use of (1) an Escherichia coli replicon, (2) a thiostrepton (Th)- and a streptomycin/spectinomycin-resistance gene for selection in Streptomyces, (3) a 3.5-kb fragment of the Streptomyces integrative plasmid pSAM2 containing its xis and int genes as well as its attachment site, attP, to direct the integration of the vectors at the chromosomal pSAM2 attachment site attB, (4) the origin of transfer of the IncP broad-host-range plasmid RK2 which allowed the mobilization of the vectors from E. coli to S. lividans, and (5) the Th-inducible tipA promoter to permit regulated transcription of cloned genes. We demonstrated that pPM927, a plasmid which contained all of these elements, was able to transfer cloned fragments from E. coli to S. lividans by conjugation, stably integrate into the chromosome, and express cloned genes from the tipA promoter. Furthermore, since pPM927 contained the pBR322 replicon, cloned fragments could be conveniently recovered from the S. lividans chromosome for analysis in E. coli by cleavage of genomic DNA isolated from transformed strains, intramolecular ligation and transformation. Since we have shown that the pSAM2 attB site forms part of a conserved prokaryotic tRNA gene, these integrative vectors are potentially useful tools for analysis and expression of genes in diverse bacteria.

Actinomycetales↗

Screening and surveillance of patients at high risk for malignant melanoma result in detection of earlier disease.

Screening, surveillance, and educational programs have been recommended for members of hereditary melanoma kindreds with dysplastic nevi, who are at very high risk for melanoma. For melanomas detected in a surveillance program offered to 555 such persons, the average thickness was 0.52 mm for 28 surveillance incident melanomas, 0.55 mm for 64 nonsurveillance incident melanomas, and 1.44 mm for 48 index lesions (p less than 0.001). The proportion of cases with level I or II invasion was 60.8%, 58.3%, and 36.2% respectively (p = 0.002). The nonsurveillance incident melanomas were diagnosed before entry into the surveillance program, but these patients were presumably aware of the earlier occurrence of two index melanomas in their families. These findings are consistent with a favorable effect of surveillance and education in a high-risk population and suggest that patient factors as well as physician factors may contribute to early diagnosis.

Dysplastic Nevus Syndrome↗

LH and FSH secretion and responses to GnRH and TRH in patients with clinically functionless pituitary adenomas.

Serum concentrations of LH and FSH and their response to the separate administration of GnRH (100 micrograms i.v.) and TRH (200 micrograms i.v.) have been studied preoperatively in 12 patients with a clinically functionless pituitary adenoma, of whom nine (3F: 6M) were found to secrete gonadotrophins in vitro. In three patients with a gonadotrophin-secreting adenoma (GSA) the pulsatile release of LH and FSH was also assessed preoperatively. An elevated serum FSH was recorded in six of nine patients with a GSA, and was subnormal in one, whilst an elevated LH was recorded in only two and was subnormal in six. A doubling of LH occurred in only four of the nine patients after GnRH and in three of six after TRH. None of the three patients with a non-GSA was shown to have an aberrant response to GnRH or TRH. In patients with a GSA, pulsatile release of LH and FSH was usually asynchronous and neither hormone demonstrated any regular harmonic pattern. These data show that in patients with a GSA the serum FSH level is usually elevated but this is not invariable, and the LH may well be low. Pathological responses of LH are frequently found following the administration of either GnRH or TRH and these stimulation tests should be performed separately in patients presenting with a clinically 'non-functioning' pituitary tumour to assist in the preoperative diagnosis. The absence of normal LH and FSH pulsing also appears to be a feature of GS adenomas, and suggests that tumorous gonadotrophin secretion is not under physiological control by hypothalamic GnRH.

Adenoma↗

Streptomyces hygroscopicus has two glutamine synthetase genes.

Streptomyces hygroscopicus, which produces the glutamine synthetase inhibitor phosphinothricin, possesses at least two genes (glnA and glnB) encoding distinct glutamine synthetase isoforms (GSI and GSII). The glnB gene was cloned from S. hygroscopicus DNA by complementation in an Escherichia coli glutamine auxotrophic mutant (glnA). glnB was subcloned in Streptomyces plasmids by insertion into pIJ486 (pMSG3) and pIJ702 (pMSG5). Both constructions conferred resistance to the tripeptide form of phosphinothricin (bialaphos) and were able to complement a glutamine auxotrophic marker in S. coelicolor. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of S. lividans(pMSG5) revealed a highly overexpressed 40-kilodalton protein. When GS was purified from this strain, it was indistinguishable in apparent molecular mass from the 40-kilodalton protein. The nucleic acid sequence of the cloned region contained an open reading frame which encoded a protein whose size, amino acid composition, and N-terminal sequence corresponded to those of the purified GS. glnB had a high G + C content and codon usage typical of streptomycete genes. A comparison of its predicted amino acid sequence with the protein data bases revealed that it encoded a GSII-type enzyme which had previously been found only in various eucaryotes (47 to 50% identity) and nodulating bacteria such as Bradyrhizobium spp. (42% identity). glnB had only 13 to 18% identity with eubacterial GSI enzymes. Southern blot hybridization experiments showed that sequences similar to glnB were present in all of the five other Streptomyces species tested, as well as Frankia species. These results do not support the previous suggestion that GSII-type enzymes found in members of the family Rhizobiaceae represent a unique example of interkingdom gene transfer associated with symbiosis in the nodule. Instead they imply that the presence of more than one gene encoding GS may be more common among soil microorganisms than previously appreciated.

Amino Acid Sequence↗

Evaluation of the associations between carotid artery atherosclerosis and coronary artery stenosis. A case-control study.

To evaluate the consistency, strength, and independence of the relation of carotid atherosclerosis to coronary atherosclerosis, we quantified coronary artery disease risk factors and extent of carotid atherosclerosis (B-mode score) in 343 coronary artery disease patients and 167 disease-free control patients. In univariable analyses, there was a strong association between coronary status and extent of carotid artery disease in men and women older than and younger than 50 years (p less than 0.001 for men and women greater than 50 years, p less than 0.001 for women less than or equal to 50 years, p = 0.045 for men less than or equal to 50). The relation remained strong after control for age in men and women older than 50 years and in women younger than 50 (p less than 0.001 for men and women greater than 50 years, p = 0.003 for women less than or equal to 50) but did not persist after control for age in men younger than 50. Logistic models that included coronary disease risk factors, with or without B-mode score, as independent variables and presence or absence of coronary disease as the outcome variable indicated that the extent of carotid atherosclerosis was a strong, statistically significant independent variable in models for men and women older than 50 years of age. Next, we examined the usefulness of B-mode score as an aid in screening for coronary artery disease in men and women older than 50 years. Classification rules, both including and excluding B-mode score, were developed based on logistic regression and, for comparison, recursive partitioning (decision trees). The performance of these rules and the bias of their performance statistics were estimated. The improved classification of the study sample when B-mode score was incorporated in the rule was statistically significant only for men (p = 0.015). However, the addition of B-mode score was found to 1) increase the median discrimination score for both sex groups based on the logistic model, and 2) yield better sensitivities and specificities for rules based on recursive partitioning. Thus B-mode score is strongly, consistently, and independently associated with coronary artery disease in patients older than 50 and is at least as useful as well-known risk factors for identifying patients with coronary artery disease.

Aging↗

On limits to perception and pattern recognition.

We propose certain general conditions that we believe are reasonable for any pattern recognition algorithm. We find that these conditions give rise to paradoxical identification. The algorithms are incapable of distinguishing composite patterns and must be able to distinguish patterns at an atomistic level.

Algorithms↗

The effect of beta blockade on single photon emission computed tomographic (SPECT) thallium-201 images in patients with coronary disease.

We evaluated the effect of beta blockers on thallium-201 (Tl-201) single photon emission computed tomographic (SPECT) imaging in 12 patients with coronary disease using an automated computer algorithm. Maximal exercise heart rate and blood pressure were reduced and exercise time was increased with beta blockers. Estimated stress defect size decreased from 47 +/- 36.3 gm during placebo treatment to 32 +/- 27.1 gm during beta blocker therapy (-32%; p less than 0.01). The placebo treatment redistribution defect was estimated to be 28 +/- 29.8 gm. It fell to 15 +/- 23.3 gm with beta blockade (-46%; p less than 0.005). All patients had a stress Tl-201 defect during placebo treatment and eight had redistribution defects consistent with residual scar. During beta blocker therapy, 2 of 12 patients had normal stress-redistribution studies and only five patients had redistribution defects. Beta blockade can reduce exercise and redistribution Tl-201 SPECT defect size significantly while simultaneously increasing exercise time and reducing angina. Beta blockers may unmask or may eliminate evidence of redistribution. Tl-201 SPECT imaging may be useful in defining the reduction in ischemia produced by cardiac drugs.

Adrenergic beta-Agonists↗

Polyuric states in man.

This chapter reviews the pathophysiological basis for the mechanisms of polyuria and discusses the causes in detail. A small proportion of patients with CDI are of the idiopathic type, with the majority of causes due to trans-spenoidal surgery, head injury following road traffic accidents, and an autoimmune variant. Indirect methods of investigating polyuria are inaccurate in a significant proportion of cases, and the incorporation of measurements of plasma AVP into a water-deprivation test or hypertonic saline infusion can improve diagnostic accuracy. Non-osmotic tests of AVP secretion are of no value in the differential diagnosis of polyuria. Most patients with CDI can maintain water homeostasis with adequate fluid intake, but desmopressin is a convenient, effective and safe therapy which is recommended on both social and medical grounds. Treatment of NDI remains problematic, as neither thiazide diuretics or indomethacin can completely abolish polyuria, and fluid intake remains of primary importance.

Diabetes Insipidus↗