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Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 451 records · Page 25Linked to original sources

Long-range chromosomal mapping of the carcinoembryonic antigen (CEA) gene family cluster.

A long-range physical map of the carcinoembryonic antigen (CEA) gene family cluster, which is located on the long arm of chromosome 19, has been constructed. This was achieved by hybridization analysis of large DNA fragments separated by pulse-field gel electrophoresis and of DNA from human/rodent somatic cell hybrids, as well as the assembly of ordered sets of cosmids for this gene region into contigs. The different approaches yielded very similar results and indicate that the entire gene family is contained within a region located at position 19q13.1-q13.2 between the CYP2A and the D19S15/D19S8 markers. The physical linkage of nine genes belonging to the CEA subgroup and their location with respect to the pregnancy-specific glycoprotein (PSG) subgroup genes have been determined, and the latter are located closer to the telomere. From large groups of ordered cosmid clones, the identity of all known CEA subgroup genes has been confirmed either by hybridization using gene-specific probes or by DNA sequencing. These studies have identified a new member of the CEA subgroup (CGM8), which probably represents a pseudogene due to the existence of two stop codons, one in the leader and one in the N-terminal domain exons. The gene order and orientation, which were determined by hybridization with probes from the 5' and 3' regions of the genes, are as follows: cen/3'-CGM7-5'/3'-CGM2-5'/5'-CEA-3'/5'-NCA-3'/5'-CGM1- 3'/3'-BGP-5'/3'- CGM9-5'/3'-CGM6-5'/5'-CGM8-3'/PSGcluster/qter.

Amino Acid Sequence↗

Over-expression of fibroblast growth factors in Xenopus embryos.

A number of forms of fibroblast growth factor (FGF) were over-expressed within Xenopus embryos by injection of synthetic FGF mRNAs into fertilized eggs. Injected embryos showed abnormalities in development which were mainly secondary to a disruption of gastrulation movements. The effects observed after injection of bFGF mRNA, however, were much less severe than those observed after injection of an altered form of bFGF mRNA which differs only by the addition of a signal sequence for secretion, or of another member of the FGF family, kFGF, which is normally efficiently secreted. All forms of FGF caused the induction of mesoderm in animal cap explants isolated from blastulae, but the amount of bFGF mRNA required to induce the formation of significant levels of mesoderm was higher by a factor of over a hundred than that of the FGFs which contain a signal sequence for secretion. Over-expressed bFGF accumulated in the nuclei of blastulae but did not necessarily cause mesoderm formation. These results show that FGFs must be secreted from the cells in which they are synthesised in order to act efficiently as mesoderm inducing factors and suggest that bFGF itself, which does not contain a signal sequence for secretion, is unlikely to be directly involved in mesoderm induction during early embryonic development.

Animals↗

A microbiological comparison between acute and complicated appendicitis.

Bacteria recovered from appendiceal specimens from 20 patients with acute appendicitis were compared with those recovered from 19 patients with complicated (gangrenous or perforative) appendicitis. Specimens of both peritoneal fluid and appendiceal tissue from patients with acute appendicitis yielded smaller numbers and fewer species of bacteria in culture than did specimens from patients with more complicated disease (2.3 strains per specimen for the former; 9.9 strains per specimen for the latter). Bacteria were recovered from all 13 cultures of specimens of appendiceal tissue and from 13 of 18 cultures of specimens of peritoneal fluid obtained from patients with gangrenous and perforative appendicitis; however, only eight of 17 cultures of appendiceal specimens and seven of 18 cultures of peritoneal fluid specimens from patients with acute appendicitis yielded bacteria. These findings suggest that some bacteria traverse the intact appendiceal wall prior to perforation and that progressive infection and subsequent tissue damage and necrosis allow larger numbers and varieties of bacteria to move through appendiceal wall tissue and into the peritoneal cavity.

Acute Disease↗

Role of tolerance in cloxacillin prophylaxis of experimental Staphylococcus aureus endocarditis.

The role of tolerance was investigated in the prophylaxis of Staphylococcus aureus endocarditis with cloxacillin in rats. The effect of a single dose of 500 mg/kg, two 80 mg/kg doses 3 h apart, and a single dose of 80 mg/kg, alone or in combination with a single dose of 4 mg of gentamicin/kg, were compared for a tolerant strain of S. aureus and its isogenic nontolerant variant. At all dosages, cloxacillin was significantly less effective in preventing endocarditis with the tolerant strain than with the nontolerant variant. With the high dose of cloxacillin or two successive lower doses, nearly complete protection could be obtained against the nontolerant strain. However, for the tolerant strain, only the combination of cloxacillin and gentamicin afforded almost complete protection. For the tolerant strain, no serum bactericidal activity was found at the time of bacterial challenge after an injection of any dose of cloxacillin. These results suggest that the in vitro phenomenon of tolerance may have relevance in vivo.

Animals↗

Awareness of need and actual use of prophylaxis: lack of patient compliance in the prevention of bacterial endocarditis.

Antibiotics are given before some medical and dental procedures to patients with congenital or acquired heart disease to prevent endocarditis. The majority of practitioners and patients are aware of the need for this prophylaxis, although in practice prophylaxis is administered infrequently. It is not known how often patients at risk for endocarditis undergo procedures which warrant the prophylactic administration of antibiotics, nor how often prophylaxis is actually administered to these patients. Two groups of adult patients and a group of children with a cardiac lesion predisposing to endocarditis were surveyed by either telephone interview or mailed questionnaire about awareness of the need for prophylaxis, procedures undergone within six months of the survey and the actual use of prophylaxis before these procedures. Of 455 patients surveyed, 371 (81.5%) responded, 258 (69.5%) of whom remembered receiving advice on prophylaxis. Recollection of advice ranged from 77% of those younger than sixty years to 48% of those aged sixty or older. The patients underwent 68 procedures for which prophylaxis was definitely indicated and 71 procedures with a possible indication for prophylaxis; 127 (91%) of these procedures were dental. Antibiotics were allegedly administered before the procedure to 31 patients (22%). There is marked discrepancy between recollection of the advice and actual use of prophylaxis. In view of this it is likely that patients often undergo procedures without antibiotic protection; however, only a few of these patients develop endocarditis.

Adolescent↗

Effects of oral testosterone undecanoate on growth, body composition, strength and energy expenditure of adolescent boys.

OBJECTIVE: We determined the effect of 3 months of daily, 40 mg oral testosterone undecanoate on growth, body composition, hand grip and quadriceps muscle strength, and total free-living daily energy expenditure in boys with constitutionally delayed puberty. DESIGN: Double blind, placebo controlled study. PATIENTS: Eighteen boys with constitutionally delayed puberty, mean (SD) age 13.2 (1.6) years. MEASUREMENTS: Body composition measurements were made by skinfold thickness, bioelectrical impedance and stable isotope dilution (H2(18)O) methods. Energy expenditure was assessed by the doubly-labelled water (2H2(18)O) technique. RESULTS: Height velocity increased from 5.4 (0.8) to 8.1 (0.6) cm/year (P < 0.05) in the 3 months after active therapy. Fat-free mass increased more with therapy (2.7 (0.3) kg) over the 6-month study period than with placebo (1.7 (0.4) kg, P < 0.5). Height velocity increases correlated with daily increases in fat-free mass (r = 0.68, P = 0.005) in the study group as a whole. Energy expenditure and muscle strength increased similarly in both groups. Predicted adult height decreased in the group which was treated with testosterone undecanoate. CONCLUSIONS: Testosterone undecanoate (40 mg daily for 3 months) significantly increased height velocity and fat-free mass velocities after 6 months but not muscle strength, endurance or total daily energy expenditure.

Administration, Oral↗

Case report: neuropathology of methyl bromide intoxication.

The neuropathological findings in a man and his dog both of whom died after acute exposure to methyl bromide are presented. The dog had cerebral oedema, most marked in the depths of cortical sulci. The man survived 30 days after the initial illness and his brain contained well-defined symmetrical lesions in the mammillary bodies and inferior colliculi. He also had a peripheral neuropathy and lymphocytic thyroiditis. The pathology in the central nervous system has features resembling Wernicke's encephalopathology; the mechanism by which methyl bromide may produce such lesions is discussed.

Adult↗

Sucrose fermentation by Fusobacterium mortiferum ATCC 25557: transport, catabolism, and products.

Studies of sucrose utilization by Fusobacterium mortiferum ATCC 25557 have provided the first definitive evidence for phosphoenolpyruvate-dependent sugar:phosphotransferase activity in the family Bacteroidaceae. The phosphoenolpyruvate-dependent sucrose:phosphotransferase system and the two enzymes required for the dissimilation of sucrose 6-phosphate are induced specifically by growth of F. mortiferum on the disaccharide. Monomeric sucrose 6-phosphate hydrolase (M(r), 52,000) and a dimeric ATP-dependent fructokinase (subunit M(r), 32,000) have been purified to electrophoretic homogeneity. The physicochemical and catalytic properties of these enzymes have been examined, and the N-terminal amino acid sequences for both proteins are reported. The characteristics of sucrose 6-phosphate hydrolase and fructokinase from F. mortiferum are compared with the same enzymes from both gram-positive and gram-negative species. Butyric, acetic, and D-lactic acids are the end products of sucrose fermentation by F. mortiferum. A pathway is proposed for the translocation, phosphorylation, and metabolism of sucrose by this anaerobic pathogen.

Acetates↗

Trial of intensive compared with weekly speech therapy in preschool children.

Forty two preschool children referred to a speech therapy department were randomly allocated to receive intensive individual speech therapy or the more traditional once weekly approach. Boys and minority ethnic groups were referred most frequently. Speech therapy improved expression more than comprehension, as measured on Reynell scales. The mean improvements were 0.5 SDs (95% confidence intervals (CI) 0.3 to 0.7) and 0.3 (95% CI 0.1 to 0.5) respectively. There was a greater improvement in children receiving intensive compared with weekly therapy in the expression scores (0.8 SDs (95% CI 0.5 to 1.1) v 0.2 SDs (95% CI -0.1 to 0.5]. White and non-white children had similar improvements in comprehension scores but white children had greater improvement in expression scores (1.1 SDs v 0.3 SDs). This difference was seen in both therapy groups. Randomised trials are useful in the evaluation of speech therapy in children.

Child, Preschool↗

Identification of two promoters within human cytomegalovirus morphologic transforming region II.

A 980-bp subfragment of human cytomegalovirus (HCMV) strain Towne has been previously identified as morphologic transforming region II (mtrII) because of its ability to induce focal transformation of NIH 3T3 cells. Transcripts from this region, which could encode the three open reading frames (ORFs), 79, 83, and 34 amino acids (aa), detected by DNA sequence analysis, are expressed early during HCMV infection. In this report, the mRNA start sites for promoters (P1 and P2) were mapped within Towne mtrII by primer extension using RNAs isolated from transformed NIH 3T3 cells. The Towne mtrII promoters exhibited similar activities to the SV40 enhancerless early promoter. Equivalent promoter activities were detected within the mtrII colinear nontransforming region from HCMV strain Tanaka. Two subclones of Towne mtrII (5' 440-bp and 3' 540-bp), each containing one promoter, were generated utilizing a unique BgII site which also interrupted the 79-aa ORF. In transfection assays, neither the 5' 440-bp promoter subclone containing a truncated 79-aa ORF nor the 3' 540-bp subclone containing intact 83- and 34-aa ORFs exhibited transforming activity. These data indicated that transformation by HCMV mtrII did not occur by promoter insertion. The identification of these early promoters will allow further studies on the regulation of important HCMV early genes known to be involved in viral/host interactions.

3T3 Cells↗

Plasma norepinephrine responses to head-up tilt are misleading in autonomic failure.

The failure of plasma norepinephrine to rise during upright posture is accepted as a diagnostic sign of autonomic nervous failure in patients with postural hypotension. Our clinical experience has been that this test is misleading, with an increase in plasma norepinephrine commonly occurring. To test whether this might result from absent reflex postural venous constriction lowering cardiac output and plasma norepinephrine clearance, we measured norepinephrine plasma kinetics during recumbency and 30 degrees head-up tilting in six patients with pure autonomic failure and eight healthy subjects. Mean arterial pressure fell by 54 +/- 8 mm Hg with head-up tilt in the patients with pure autonomic failure. The plasma norepinephrine concentration (arterial sampling) increased 73 +/- 29 pg/ml (mean difference +/- SED, p less than 0.02), solely because of a 36% reduction in the clearance of norepinephrine from plasma (0.78 +/- 0.09 l/min, p less than 0.0001). In normal subjects, plasma norepinephrine concentration rose by 112 +/- 20 pg/ml (p less than 0.001), largely because of a 24% increase in norepinephrine spillover to plasma (190 +/- 20 ng/min, p less than 0.005). When the postural fall in blood pressure and cardiac output in the pure autonomic failure patients was prevented by the selective venoconstrictor dihydroergotamine (10 micrograms/kg i.v.), no fall in plasma clearance or rise in plasma concentration of norepinephrine occurred. Measurement of the change in plasma norepinephrine with postural stimulation in patients with orthostatic hypotension is not a reliable diagnostic test for autonomic failure because elevations can occur in the plasma concentration that are entirely attributable to reduced plasma norepinephrine clearance.

Autonomic Nervous System Diseases↗

Bacterial meningitis in children: pathophysiology and treatment.

Recent studies of the pathophysiology of bacterial meningitis have suggested that the development of neuronal injury is related to the release of vasoactive substances or alteration of blood-brain barrier permeability. Cerebral edema, increased intracranial pressure (ICP), systemic hypotension, decreased cerebral perfusion pressure, vascular inflammation, thrombosis, and a variety of other vascular changes may result in global or regional reductions in cerebral blood flow (CBF), which contribute to this insult. Approximately one-third of infants and children with bacterial meningitis will have markedly reduced CBF, and even in those children with normal total flow, regional hypoperfusion is common. Reduced CBF is associated with cerebral edema and a poor prognosis. A poor prognosis also is associated with reduced cerebral perfusion pressure. This occurs early in the course of meningitis and is primarily due to increased ICP rather than systemic hypotension. Autoregulation is preserved, suggesting that local ischemic tissue injury is more related to factors such as regional edema formation, focal vascular pathology, or specific intrinsic flow/metabolic abnormalities than to a reduction in systemic blood pressure. In contrast with other acute CNS insults, CBF/PCO2 reactivity is well preserved in many patients with meningitis; this raises the possibility that hyperventilation may cause further ischemic injury in those patients with marginal CBF. Although it is still unclear that treatment of increased ICP will affect outcome, we propose a treatment paradigm based on the results of neuroimaging studies and ICP measurements.

Animals↗

A chromosome 9 deletion in Plasmodium falciparum results in loss of cytoadherence.

Many lines of Plasmodium falciparum undergo a deletion of the right end of chromosome 9 during in vitro culture accompanied by loss of cytoadherence and gametocytogenesis. Selection of cytoadherent cells from a mixed population co-selects for those with an undeleted chromosome 9 and the selected cells produce gametocytes. The deletion also results in loss of expression of PfEMP1, the putative cytoadherence ligand, suggesting that PfEMP1 or a regulatory gene controlling PfEMP1 expression and gametocytogenesis may be encoded in this region. We have isolated several markers for the deleted region and are currently using a YAC-P. falciparum library to investigate this region of the genome in detail.

Animals↗