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Biomedical subjects

D Newton

Publications and source records attributed to D Newton.

At least 37 records · Page 2Linked to original sources
PubMed1994

Superantigenic properties of the group A streptococcal exotoxin SpeF (MF).

Streptococcal pyrogenic exotoxin F (SpeF), previously referred to as mitogenic factor, is a newly described potent mitogen produced by group A streptococci. To investigate whether this protein belongs to the family of microbial superantigens, we analyzed the cellular and molecular requirements for its presentation to T cells and compared it with the known streptococcal superantigen pyrogenic exotoxin A (SpeA) and the nonspecific polyclonal T-cell mitogen phytohemagglutinin (PHA). SpeF and SpeA were efficiently presented by autologous antigen-presenting cells (APCs) and an allogeneic B lymphoma cell line, Raji. In contrast, the monocytic cell line U937, which does not express major histocompatibility complex (MHC) class II molecules, failed to present SpeF as well as SpeA but supported the response to PHA. Thus, the presentation of SpeF by APCs was class II dependent but not MHC restricted. The requirement for HLA class II was further supported by the ability of anti-HLA-DQ monoclonal antibody to block the SpeF-induced proliferative response by 75 to 100%. Paraformaldehyde (PFA) fixation of autologous APCs resulted in an impaired ability of SpeF and SpeA to induce optimal T-cell proliferation. In contrast, fixation of Raji cells did not affect the induced proliferation. The stimulatory effect of PHA remained unaffected by both the use of PFA-fixed APCs and the addition of the HLA class II-specific monoclonal antibodies. The addition of a supernatant enriched in interleukin 1 and interleukin 6 to fixed autologous APCs resulted in an increased SpeF-induced response; thus, the impairment was not due to a requirement for processing, but, rather, costimulatory factors produced by metabolically active APCs were needed. SpeF was found to preferentially activate T cells bearing V beta 2, 4, 8, 15, and 19, as determined by quantitative PCR. The data presented clearly show that SpeF is a superantigen. We also studied the prevalence of the speF gene in clinical isolates by Southern blot analyses, and the gene could be detected in 42 group A streptococcal strains, which represented 14 serotypes.

Antigen-Presenting Cells↗
PubMed1993

Mosaic tetrasomy 8p.

We report on a patient with mosaic tetrasomy 8p [46,XX/47,XX+i(8p)]. The patient has 2 fused vertebrae, abnormal ribs, congenital heart defects, agenesis of corpus callosum, hypotonia, and delayed development. The patient's developmental delays are most marked in receptive and expressive language skills, with more moderate delays on cognitive, sensorimotor, and motor skill testing. These findings are similar to those of the 3 previously reported patients with mosaic i(8p).

Abnormalities, Multiple↗
PubMed1993

The problems of tracing a geographically widespread outbreak of salmonellosis from a commonly eaten food: Salmonella typhimurium DT193 in north west England and north Wales in 1991.

Geographically widespread outbreaks involving commonly isolated organisms and where the vehicles of infection are commonly eaten foodstuffs pose particular difficulties at a technical and organizational level. An outbreak of Salmonella typhimurium infection, affecting 39 people, spread over a wide area in North West England and North Wales in April and May 1991, was detected thanks to the practice of sending specimens to the national reference laboratory where phage typing and characterizing of antibiotic resistance patterns enabled the identification of a cluster of distinctive isolates (S. typhimurium DT193 resistant to sulphonamides, trimethoprim and furazolidone). An investigation, involving twenty environmental health departments in addition to health authorities and the Public Health Laboratory Service, showed an association between the illness and eating loose sliced cooked ham (P = 0.004). Detailed tracing of the chain of supply of the ham showed this to be particularly cooked ham originating from a single small local producer (P = 0.00003). Further investigation of that producer revealed that a batch of ham distributed on one day in early April was undercooked due to a malfunction in cooking equipment.

Adolescent↗
PubMed1993

A comparison of techniques in the assessment of chest wall thickness and composition.

The thickness and composition of defined regions of the anterior chest wall are important factors in the assessment of pulmonary plutonium by low-energy x ray counting. Estimates of these quantities are reported for seven male subjects investigated by three laboratories using ultrasonic methods and by a fourth laboratory using magnetic resonance imaging. No important bias was found in any one laboratory's estimates of chest wall thickness relative to those of the others, but differences of up to 6 mm were noted for individual subjects. The discrepancies are believed principally to reflect the different sampling regimes adopted to reach a representative mean chest wall thickness over the region of interest from measurements at selected points. The adipose-tissue component was consistently found to be lower when assessed by magnetic resonance imaging compared with estimates by ultrasound, but the differences were unimportant in the context of plutonium assessment.

Adipose Tissue↗
PubMed1993

Human uptake of 137Cs in mutton.

The uptake of radiocesium from mutton contaminated by fallout from the Chernobyl reactor accident has been studied in eight healthy male volunteers. Each subject consumed, on adjacent days, two meals prepared from the mutton containing a total of 0.8 kBq 137Cs. The elevation and subsequent decline in whole-body content were determined from body radioactivity measurements prior to the meals and at intervals up to 15 wk afterwards. Clearance of 137Cs between 1 and 15 wk showed a biological half-time of 102 +/- 24 (SD) d, (range 84-154 d). The fraction cleared with this half-time was 80 +/- 4% (range 72-85%). No attempt was made to determine the early retention and excretion but, if the ICRP's assumption of 10% clearance with a 2-d half-life were valid, the data would indicate an average uptake (f1) of 89%, i.e., marginally lower than the value of 100% assumed in setting limits on intake.

Accidents↗
PubMed1993

Metabolism of injected plutonium in two healthy men.

The metabolism of plutonium has been studied following intravenous injection of 237Pu as Pu (IV) citrate into two healthy male volunteers. Measurements of the tracer in samples of blood and excreta were made by gamma-ray spectrometry, and patterns of organ uptake were investigated through serial measurements with a scintillation counter viewing the liver and selected skeletal sites. Excretion in urine and feces measured during the first 3 wk accorded closely with the patterns deduced by Durbin from the report of Langham et al. on patients injected with 239Pu. However, concentrations in blood were roughly twice those suggested by Durbin during most of the 14 d covered by our measurements. In one subject, the liver deposit increased to a plateau after about 21 d, at roughly 55% of the injection; in the other, the increase was prolonged, reaching about 70% after several months.

Aged↗
PubMed1993

Cytotoxic ribonucleases and chimeras in cancer therapy.

Ribonucleases serve as cytotoxic agents during host defense and physiological cell death pathways. In bacteria, higher plants, and mammals, ribonucleases appear to bind cells, enter the cytosol where they degrade RNA, and kill the target cell. This process functions in interstrain competition in bacteria, in the death of incompatible pollen in higher plants, and likely plays a role in the antiparasitic and anticancer activity of eosinophils in man. One can alter the target cell specificity of RNases by coupling them to new cell-binding domains. Chemically coupling RNases to new binding moieties or fusing RNase genes to antibody genes results in chimeric molecules with specified cell-type cytotoxicity. Thus, one can target one's own host defense cytotoxins to select cell populations. This allows the use of human proteins, instead of plant and bacterial toxins, in the construction of immunotoxins. RNases also can be engineered to kill cells by cytosolic expression or to kill viruses by packaging into viruses. Engineering RNases into cell-type-specific cytotoxins may result in a new class of therapeutic reagents. We review a number of interesting physiological cell cytotoxicity pathways utilizing RNases and then describe the recent results on engineering RNases for therapeutic use.

Amino Acid Sequence↗
PubMed1992

The weakness of old age is not due to failure of muscle activation.

Maximum voluntary force and cross-sectional area (MVF and CSA) of the human adductor pollicis muscle were compared in groups of young (19-55 years, mean = 28, n = 53) and elderly (74-90 years, mean = 80, n = 39) subjects, of both sexes. Despite the elderly subjects being in good health and active outdoors, they were considerably weaker than the young subjects, their MVF/CSA being 26 +/- 3% (mean +/- SEM) lower. It was found that both young and elderly subjects could fully activate their muscles. Therefore the muscle weakness of old age does not appear to be due to reduced activation and must be caused by another mechanism, possibly biochemical in nature.

Adult↗
PubMed1992

Elevation of lead in human blood from its controlled ingestion in beer.

1. Nine volunteers ingested high levels of lead in beer over a 28-d period. The increase in blood lead varied by a factor of about two. There was a similar two-fold variability in the whole-body uptake (mean 14%) of a single oral dose of the short-lived tracer 203Pb. 2. The average elevations led to estimates of the potential increment from consumption of alcoholic beverages which accord broadly with epidemiological observation and which, if relevant to intakes of lead in table wine, raise the possibility of considerably elevated levels in the blood of avid consumers. 3. Rate constants inferred for removal of stable lead from blood were lower than reported following intake of the tracer, reflecting feedback of lead from other compartments.

Adult↗
PubMed1991

Metabolism of injected barium in six healthy men.

Data are presented on the early metabolism and long-term retention of 133Ba (half-life 10.74 y) injected into six healthy male volunteers at ages 25-81 y. The tracer appeared to be mainly skeletal within several days, much earlier than predicted by the ICRP's model of alkaline earth metabolism. Excretion was mainly fecal, the relative fecal:urinary clearance up to 14 d ranging from 6 to 15 in the six subjects. The whole-body retention at 50 d (mean 8%, range 4.5 to 12%) was similar to that inferred from published data on the retention of injected Ra in man (mean 7%, range 3-13%). For about 1 y thereafter, the retention of Ba could be represented by simple power functions of time, with the rate of loss correlating with the excretory plasma clearance rate inferred over the first 4 d. In the subject aged 81 y, the pattern differed from that established following an earlier injection at age 60, but the differences were not necessarily related to advancing age.

Adult↗
PubMed1990

Metabolism of Ca and Sr in late adult life.

Data are presented on the metabolism of Ca and Sr in a healthy male volunteer who, in a series of investigations conducted between the ages of 53 and 82 y, received controlled intakes of 45Ca, 47Ca, or 85Sr. No age-related trends were established, either in factors affecting the skeletal deposition of the tracers or in their subsequent retention studied for up to 462 d after intake. The data thus lend support to an important working postulate in the ICRP's model of alkaline earth metabolism.

Aged↗
PubMed1990

Human metabolism of arsenobetaine ingested with fish.

1. Six volunteers ingested 74As-labelled arsenobetaine with a fish meal. The retention and distribution of the tracer were studied by body radioactivity measurements. 2. The tracer became rapidly dispersed in soft tissues, with no major concentration in any localized organ or region. 3. In all subjects less than 1% of the ingested activity remained in the body after 24 days. 4. Any losses from the skin were minor in relation to those by other routes of excretion.

Adult↗
PubMed1989

Effect of subnutrition on normalized muscle force and relaxation rate in human subjects using voluntary contractions.

1. Muscle weakness and wasting are well-known consequences of subnutrition, but there have been no published comparisons of these variables in a single muscle or muscle group. We report voluntary force measurements of adductor pollicis muscle in 11 subnourished patients normalized for their cross-sectional areas. We also report normalized relaxation rates of these contractions and the results are compared with those obtained in 40 healthy normally nourished subjects. 2. Normalized muscle force was no different in the subnourished group. However, relaxation rate was significantly slower than in the control group.

Adult↗
PubMed1989

Effect of age on voluntary force and cross-sectional area of human adductor pollicis muscle.

Muscle weakness accompanies ageing but its causes are still uncertain. We report maximum voluntary force measurements of adductor pollicis muscle, normalized for cross-sectional area, in twenty-three elderly subjects. Normalized force was lower in the elderly compared with a group of fifty-five young adult subjects by 27 +/- 4% (S.E.M.). This shows that atrophy alone is not the cause of the weakness of old age.

Adult↗
PubMed1985

Selective effects of CAPP1-calmodulin on its target proteins.

Occupancy of one of the two phenothiazine-binding sites on calmodulin does not significantly decrease the affinity of calmodulin for its target proteins; however, it does affect the ability of calmodulin to activate some enzymes. Previously we demonstrated that a covalent adduct of calmodulin with one molecule of phenothiazine (CAPP1-calmodulin) is an antagonist for the calmodulin-dependent enzymes, cAMP phosphodiesterase and myosin kinase, and a partial agonist for calcineurin. We now show that CAPP1-calmodulin is a full agonist for glycogen synthase kinase and phosphorylase kinase. Unlike phenothiazines, CAPP1-calmodulin is specific for calmodulin-regulated proteins; it has no effect on protein kinase C. With the exception of phosphorylase kinase, occupancy of two phenothiazine-binding sites completely eliminates the ability of calmodulin to activate these proteins. Thus, the study of the interaction of CAPP1-calmodulin with calmodulin target proteins demonstrates that calmodulin interacts differently with different proteins. This is confirmed by studies of the effect of calmodulin fragments, 1-77 and 78-148, on calmodulin-regulated enzymes.

Animals↗
PubMed1984

The uptake by man of cadmium ingested in crab meat.

Seven male volunteers with normal iron stores ate the brown meat from crabs whose diet had contained radioactive cadmium-115m. Systemic uptake of cadmium by the volunteers, derived from measurements of their residual body radioactivity several weeks after intake, averaged 2.7 +/- 0.9 (se)%, essentially as found by others in studies with extrinsically labelled food.

Adult↗