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Biomedical subjects

T Jones

Publications and source records attributed to T Jones.

At least 271 records · Page 15Linked to original sources

Interrelationships between regional blood flow, blood volume, and ventilation in supine humans.

Positron emission tomography was used to measure alveolar gas volume, pulmonary blood volume (VB), regional alveolar ventilation (VA), and the regional ventilation-to-perfusion ratio (VA/Q) in a transaxial slice at midheart level in eight supine subjects and one prone normal subject during quiet breathing. These relationships allow regional blood flow (Q) to be calculated as VA/(VA/Q). No significant differences between right and left lung were found. Within the volume studied, which excluded the peripheral 2 cm of the lung, there was an exponential increase in Q by 11%/cm from 1.2 ml.min-1.cm-3 in the upper (ventral) to 3.5 ml.min-1.cm-3 in the lower (dorsal) lung regions, explaining 61% of the total variation within groups, whereas the horizontal gradient only explained 7% (right lung; supine subjects). Similar gravitational gradients were found in the single prone subject. VA and Q were well matched except at the dorsal lung thoracic border where low values of VA/Q due to a reduction in ventilation were occasionally found even in these normal subjects. VB and Q were reasonably well matched, implying that variations in vascular transit time due to gravity are kept to a minimum. The coefficient of local variation of peripheral vascular transit times (VB/Q) (33%) was, therefore, less than would have been expected if VB and Q were uncorrelated (57%).

Adult↗

Effect of creep feeding on selected microflora and short-chain fatty acids in the ileum of weanling pigs.

Pigs cannulated at the ileum were used to investigate the effect of creep feeding on specific intestinal microflora and VFA and lactate concentrations. In two replicate trials performed 50 d apart, a total of 24 15-d-old nursing pigs from seven sows were cannulated in the terminal ileum and randomly assigned to two test groups. One group was allowed access to a creep diet, whereas the other group was denied access to the diet by removal from the farrowing crate. Ileal samples were collected at 19, 22, 26, and 29 d of age (preweaning) and at 33, 36, and 40 d of age (postweaning). Samples were assayed for total and hemolytic E. coli, total lactobacilli, pH, acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, D(-), and L(+) lactate. Creep feeding did not affect lactobacilli or E. coli concentrations (P > .05), nor did it affect short-chain fatty acid concentrations (P > .05). Most volatile fatty acid concentrations decreased (P < .05), total lactate increased (P < .05), and the proportion of E. coli that were hemolytic increased (P < .05) following weaning. Consumption of creep feed did not affect specific microbial populations or fermentative byproducts in the ileum of the young pig.

Animal Feed↗

Get off the bill hook.

In an increasingly strict financial climate increasing income is just as important as reducing costs, and so is increasing the speed at which income is collected. Tom Jones, of health care management consultants, McLean Jones McCarthy, provides some tips on how managers can deal with debtors, manage an efficient finance directorate--and get off the bill hook.

Accounts Payable and Receivable↗

The DNA region around the c-myc gene and its amplification in human tumour cell lines.

In order to study amplicons containing the c-myc locus in human tumour cells we have analysed the region around the human c-myc gene. Using pulsed field gel electrophoresis we have constructed a 1.8 Mb map of the c-myc locus using six rare-cutting endonucleases. In addition we have cloned 130 kb of continuous DNA around the c-myc gene which includes 65 kb of 5' sequence and 65 kb of 3' sequence. The first exon of the pvt-1 gene was located 59 kb 3' of the c-myc gene. Using nine neighbouring probes, covering a region of about 395 kb around the c-myc gene, we were able to determine the extent and composition of c-myc amplicons in the HL60, NCI-N417, Colo320HSR, SkBr3 and the Sk-N-MC human tumour cell lines. Furthermore we analysed the chromosomal location of amplified c-myc DNA in NCI-N417 and SkBr3 cells. Similarities and differences between the amplified DNA in the different cell lines are discussed.

Cloning, Molecular↗

Prokaryotic peptides that block leukocyte adherence to selectins.

Pertussis toxin binds target cells through the carbohydrate recognition properties of two subunits, S2 and S3, which share amino acid sequence similarity with the lectin domains of the eukaryotic selectin family. Selectins appear on inflamed endothelial cells and promote rolling of leukocytes by reversibly binding carbohydrates. S2, S3, and synthetic peptides representing their carbohydrate recognition domains competitively inhibited adherence of neutrophils to selectin-coated surfaces and to endothelial cells in vitro. These proteins and peptides also rapidly upregulated the function of the leukocyte integrin CD11b/CD18. These findings implicate mimicry of eukaryotic selectins by prokaryotic adhesive ligands and link the mechanisms underlying leukocyte trafficking to microbial pathogenesis.

Amino Acid Sequence↗

Comparison of regional myocardial blood flow in syndrome X and one-vessel coronary artery disease.

Myocardial blood flow (MBF) was measured using continuous inhalation of oxygen-15-labeled carbon dioxide, and positron emission tomography before and after intravenous dipyridamole in 13 patients with syndrome X (angina pectoris, angiographically normal coronary arteries, positive exercise test and negative ergonovine test), 7 healthy subjects and 8 patients with 1-vessel coronary artery disease (CAD). In patients with syndrome X, baseline MBF was greater than in healthy subjects and patients with CAD (1.24 +/- 0.27 vs 0.87 +/- 0.07 and 1.03 +/- 0.23 ml/g/min, respectively; p < 0.05), and more heterogeneous (34 +/- 7 vs 26 +/- 5 and 25 +/- 6, respectively; p < 0.05) as assessed by the coefficient of variation among myocardial regions < or = 2.3 cm3. After dipyridamole, MBF in patients with syndrome X was similar to that in healthy subjects (2.95 +/- 0.75 vs 3.40 +/- 0.82 ml/g/min; p = NS) and greater than in patients with CAD (1.78 +/- 0.76 ml/g/min; p < 0.05). However in patients with both syndrome X and CAD, MBF was more heterogeneous than in healthy subjects (48 +/- 12 and 48 +/- 11, respectively, vs 30 +/- 7; p < 0.01). Thus, in patients with syndrome X, MBF is abnormally heterogeneous both at baseline and after dipyridamole. These findings are compatible with the presence of dynamic alterations of small coronary arteries. Because these alterations appear to be very sparse within the myocardium, they can be undetected when myocardial perfusion, function and metabolism are assessed using conventional methods that are unable to detect small myocardial regions.

Adult↗

Molecular cloning and sequence analysis of the monkey and human tissue kallikrein genes.

Cynomolgus monkey renal kallikrein cDNA and genomic human tissue kallikrein gene were cloned. The monkey gene encodes a 257 amino acid (aa) preprokallikrein and exhibits 95% and 92% homology to the human at nucleotide (nt) and aa level, respectively. The monkey gene encodes a 233-aa mature kallikrein versus a 238-aa in human. The human kallikrein gene and urinary kallikrein both contain a Lys-162 instead of the reported Glu-162. Human, monkey and rat renal/pancreatic kallikrein genes evolve with a N-glycosylation containing domain (aa 81-87) which is absent in porcine and is non-glycosylable in mice. Only human kallikrein evolves with an additional Thr-108 and with a N-glycosylation site at aa-141.

Amino Acid Sequence↗

Organic dust exposure from compost handling: response of an animal model.

The objective of this investigation was to elucidate the pulmonary responses of an animal model to dust generated from leaf/wood compost which had caused a severe case of acute respiratory illness in an individual. Guinea pigs were exposed for 4 hr to 30 mg/m3 of aerosolized leaf/wood compost dust. Inhalation resulted in significant cellular activation and changes in pulmonary mechanics. Maximal elevation in breathing rate (increases 36%) was observed 12-18 hr postexposure. Similarly, maximal granulocyte infiltration (increases 1,600%) and activation of alveolar macrophages (increases 65%) occurred 18 hr postexposure. In contrast, maximal airway obstruction (increases 120%) occurred immediately after exposure and returned toward normal (increases 53%) by 18 hr postexposure. In several respects, the airway obstruction and pulmonary inflammation described in the animal model were comparable to the human response to compost dust. Therefore, this animal model may be useful in predicting the potential respiratory hazard associated with exposure to various organic dusts.

Agriculture↗

Gender influences counterregulatory hormone responses to hypoglycemia.

It has been generally assumed that counterregulatory hormone responses to hypoglycemia are not influenced by gender. To test this assumption, we analyzed three separate hypoglycemic insulin clamp studies in age-matched, healthy, non-obese females (n = 33) and males (n = 37). In one study (12 females, 17 males), plasma glucose level was rapidly decreased to about 57 mg/dL for 100 minutes with a 0.65-mU/kg/min insulin infusion. Despite an identical decrease in glucose level, the increase in epinephrine (361 +/- 64 v 188 +/- 38 pg/mL, P < .05), norepinephrine (132 +/- 28 v 47 +/- 19 pg/mL, P < .01), and growth hormone ([GH] 16.0 +/- 3.8 v 4.9 +/- 1.9 ng/mL, P < .05) levels, but not glucagon or cortisol levels, were significantly greater in males than in females, respectively. In the second study (10 females, eight males), a 5.0-mU/kg/min insulin infusion was used to decrease glucose levels to 55 mg/dL for 180 minutes. Epinephrine (P < .05) and GH (P < .01) responses were greater in males than in females. In a third study (11 females, 12 males), plasma glucose level was gradually decreased to about 50 mg/dL over 240 minutes. Again epinephrine (P < .01), norepinephrine (P < .01), GH (P < .05), and cortisol (P < .01) responses were nearly twofold greater in males (P < .01). Multivariate analysis of all 70 subjects identified gender as the most significant factor contributing to the epinephrine (P < .001) and norepinephrine (P < .005) responses, and also as a significant contributor to the GH response (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diagnosis of Ewing's sarcoma and peripheral neuroectodermal tumour based on the detection of t(11;22) using fluorescence in situ hybridisation.

Fluorescence in situ hybridisation (FISH) has been used increasingly for gene mapping and ordering probes on interphase and metaphase preparations. The association of consistent chromosomal aberrations with certain malignancies allows the possibility of using interphase cytogenetics as a diagnostic tool. In small round cell tumours of children accurate diagnosis may be difficult using existing methods. We have therefore evaluated the diagnostic potential of this technique when applied to the characteristic t(11;22) found in Ewing's sarcoma and peripheral neuroectodermal tumour (ES and PNET). Interphase nuclei were prepared from normal human foreskin fibroblasts (HFF), two Ewing's sarcoma cell lines and several fresh tumour biopsies. DNA probes each side of the breakpoint at 22q12 were labelled with biotin and digoxygenin, hybridised to chromosomes in interphase and detected in different colours. Measurements between pairs of signals arising from each copy of chromosome 22 were taken and statistical analysis performed. There was a highly significant difference (P < 0.0001) between the two populations of measurements obtained (from nuclei with and without the t(11;22)). Studying four tumours and one further ES line (blind) it was found that median values from 30 nuclei could correctly identify which samples contained the t(11;22). This application of interphase cytogenetics contributes a reliable, accurate and conceptually simple diagnostic test for ES and PNET. It may now be applied to other tumours with characteristic translocations, amplifications or deletions when suitable probes are available. This approach is likely to become a routine in clinical diagnosis.

Chromosomes, Human, Pair 11↗

Spectral analysis of dynamic PET studies.

We describe a new technique for the analysis of dynamic positron emission tomography (PET) studies in humans, where data consist of the time courses of label in tissue regions of interest and in arterial blood, following the administration of radiolabelled tracers. The technique produces a simple spectrum of the kinetic components which relate the tissue's response to the blood activity curve. From this summary of the kinetic components, the tissue's unit impulse response can be derived. The convolution of the arterial input function with the derived unit impulse response function gives the curve of best fit to the observed tissue data. The analysis makes no a priori assumptions regarding the number of compartments or components required to describe the time course of label in the tissue. Rather, it is based on a general linear model, presented here in a formulation compatible with its solution using standard computer algorithms. Its application is illustrated with reference to cerebral blood flow, glucose utilization, and ligand binding. The interpretation of the spectra, and of the tissue unit impulse response functions, are discussed in terms of vascular components, unidirectional clearance of tracer by the tissue, and reversible and irreversible phenomena. The significance of the number of components which can be identified within a given datum set is also discussed. The technique facilitates the interpretation of dynamic PET data and simplifies comparisons between regions and between subjects.

Algorithms↗

Detection of thirty-second cognitive activations in single subjects with positron emission tomography: a new low-dose H2(15)O regional cerebral blood flow three-dimensional imaging technique.

Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30-60 mCi of H2(15)O per scan and intersubject averaging to achieve statistical significance. However, intersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is presented. It is based upon high-sensitivity three-dimensional imaging and a "slow" bolus administration of < 15 mCi of H2(15)O per scan. The method is validated in four normal volunteers using control and auditory-language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demonstrated that the rCBF distribution associated with the cognitive state is detected during the arrival of radiotracer in the brain. This occurs over 30 s and constitutes a critical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuroanatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders.

Adult↗

Vasodilator reserve in collateral-dependent myocardium as measured by positron emission tomography.

Myocardial blood flow can be accurately quantitated in patients using positron emission tomography and oxygen-15 labelled water. The purpose of this study was to determine the vasodilator reserve in myocardium completely perfused by intramyocardial collateral blood flow. We hypothesized that altered relative flow reserve in such regions would correlate with the degree of ischaemia observed in these patients during exercise. The technique involves the inhalation of the positron emitting tracer C15O2 which is converted to freely diffusible H2(15)O by the lung. With rapid dynamic scanning, arterial and regional myocardial tissue concentrations can be obtained and time activity curves generated. With a two-compartment kinetic model, myocardial blood flow can be accurately quantitated over a wide range of blood flows. Five patients with stable exertional angina and normal ventricular function studies and who had an occluded major epicardial artery which completely opacified via intramyocardial collateral blood flow were studied. Myocardial blood flow (MBF) was measured both at rest and following an infusion of intravenous dipyridamole (0.56 mg.kg-1) and the results were compared with measurements obtained from a group of eight normal volunteers. During resting conditions, MBF in the control group was 0.86 +/- 0.10 ml.g-1.min-1 and in the patient group was 0.99 +/- 0.10 ml.g-1.min-1 in normally perfused myocardium (ns) and 0.86 +/- 0.14 ml.g-1.min-1 in collateral-dependent myocardium (ns). Following dipyridamole, MBF increased to 3.58 +/- 0.89 ml.g-1.min-1 in the control group and to 2.97 +/- 0.94 ml.g-1.min-1 in the normal regions of the patients (ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The organization and conservation of the human Surfeit gene cluster and its localization telomeric to the c-abl and can proto-oncogenes at chromosome band 9q34.1.

The mouse Surfeit locus contains an unusually tight cluster of six housekeeping genes (Surf-1 to -6) which are unrelated by sequence homology. Using a mouse Surfeit locus probe, a 16 kb clone has been isolated which contains the human Surf-1 and Surf-3 genes and regions of the human Surf-2 and Surf-5 genes. The organization and juxtaposition of these human Surfeit locus genes are the same as found in the mouse. Using the human clone as a biotinylated probe for fluorescence in situ hybridization (FISH) we have confirmed the location of the human Surfeit locus to chromosome band 9q34. Metaphase spreads of human chronic myeloid leukemic cells containing the t(9;22)(q34;q11) translocation involving The c-abl gene at 9q34.1 an acute nonlymphocytic leukemic cells containing the t(6;9)(q34;p23) translocation involving the can gene at 9q34.1 were analyzed by FISH using the human Surfeit clone as a probe. These analyses locate the human Surfeit locus telomeric to the c-abl and can genes at chromosome band 9q34.1.

Animals↗

Antiinflammatory effects in experimental meningitis of prokaryotic peptides that mimic selectins.

The lectin domains of two subunits of pertussis toxin, S2 and S3, share amino acid sequence similarity with the lectin domains of the eukaryotic selectin family. During inflammation, selectins appear on endothelial cells and promote recruitment of leukocytes by reversibly binding carbohydrates. Synthetic peptides representing the carbohydrate recognition domains of S2 and S3 competitively inhibited adherence of neutrophils to endothelial cells in vitro. For some peptides, this antiinflammatory effect occurred without up-regulation of the function of the leukocyte integrin CD11b/CD18. Intravenous administration of peptides to animals with meningitis disrupted recruitment of leukocytes into the cerebrospinal fluid. These findings indicate that peptides derived from prokaryotic members of the selectin family have therapeutic antiinflammatory potential.

Amino Acid Sequence↗

Congenital rubella syndrome: ophthalmic manifestations and associated systemic disorders.

Congenital rubella syndrome has a wide variety of severe ophthalmic and systemic complications. A worldwide rubella epidemic from 1963 to 1965 affected thousands of infants. This is a 20 year follow up study of patients with congenital rubella syndrome analysing the prevalence of ophthalmic disorders, associated systemic problems, and correlations among these defects. The authors statistically analysed 125 cases of congenital rubella seen in the Mayo clinic ophthalmology department over a 32 year interval. Most patients were young adults. Ocular disease was the most commonly noted disorder (78%), followed by sensorineural hearing deficits (66%), psychomotor retardation (62%), cardiac abnormalities (58%), and mental retardation (42%). Multiorgan disease was typical (88%). Ocular disease and hearing loss were frequently associated (53% had both) but not significantly correlated. A similar association existed between ocular and cardiac disease. Cataracts and microphthalmia were significantly correlated with poor visual acuity (each p < 0.0001). Glaucoma was significantly correlated with cataracts (p = 0.0002) and microphthalmia (p = 0.0024) but not poor visual acuity. Four patients with microphthalmia developed late onset glaucoma. No significant association was found between gestational age at time of maternal infection and the incidence of individual ocular conditions. However, several cardiac disorders were significantly associated with gestational age. Although new cases of congenital rubella are rare, surviving victims continue to challenge the ophthalmic and medical communities with a wide range of ocular and systemic disorders.

Age Factors↗

Two cases of 5q deletions in patients with familial adenomatous polyposis: possible link with Caroli's disease.

Two cases are reported of patients with deletions of chromosome 5q. Both have familial adenomatous polyposis (FAP) and mild mental retardation. In both, macroscopic polyposis was confined to the proximal colon in adult life (in their thirties) although microscopic adenomatosis was shown in the more distal colon with occasional single polyps. Both subjects had dermoid cysts, and congenital hypertrophy of the retinal pigment epithelium (CHRPE) was seen in case 2. Case 1 has gastroduodenal polyps and desmoid tumours; case 2 has a marfanoid habitus with an abnormal pectus, wasted calf muscles and clawing of the toes, and Caroli's syndrome. His deletion is cytogenetically more extensive than that in case 1. The paucity of adenomas in the left side of the colon suggests that FAP cannot always confidently be excluded by sigmoidoscopy alone. The expression of the disease in the colon in these cases could be milder than in the more usual autosomal dominant cases where nonsense mutations resulting from single base changes of small deletions rather than deletion of the whole gene are the usual finding.

Adenomatous Polyposis Coli↗