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Biomedical subjects

J T Jones

Publications and source records attributed to J T Jones.

At least 19 recordsLinked to original sources

Epstein-Barr virus (EBV) and Hodgkin's disease in children: incidence of EBV latent membrane protein in malignant cells.

Previous studies have detected EBV DNA by Southern blotting or in situ hybridization in biopsy material from up to 30 per cent of adult cases of Hodgkin's disease. Here we have used monoclonal antibodies specific for the EBV latent membrane protein LMP1 to examine archival material from children with Hodgkin's disease. Material from 74 cases (54 males and 20 females) was examined and 37 (30 males and 7 females) were classified as LMP1-positive in the malignant cells. LMP1 positivity was present in 4/13 (31 per cent) of lymphocyte predominant, 14/36 (39 per cent) of nodular sclerosis, 17/20 (85 per cent) of mixed cellularity, 1/2 (50 per cent) of lymphocyte depletion, and 1/3 (33 per cent) of unclassified subtypes. The positive cases by clinical stage were I 9/22 (41 per cent), II 9/20 (45 per cent), III 11/24 (46 per cent), and IV 8/8 (100 per cent). LMP1 positivity was present in 2/5 (40 per cent) children aged less than 5 years, 12/27 (44 per cent) aged 5-10 years, and 23/42 (48 per cent) aged between 10 and 15 years. The association between EBV and Hodgkin's disease in children thus appeared to be more frequent in patients with mixed cellularity and advanced disease, but examples of EBV-positive tumours were found in all histological subtypes, stages, and ages. Stepwise discriminant function analysis showed that clinical stage IV and mixed cellularity histology are independently associated with LMP1 positivity. These observations indicate that Hodgkin's disease in children is at least as strongly linked to EBV as is the disease in adults.

Adolescent

Closed-chest cardiac stimulation with a pulsed magnetic field.

Magnetic stimulators, used medically, generate intense rapidly changing magnetic fields, capable of stimulating nerves. Advanced magnetic resonance imaging systems employ stronger and more rapidly changing gradient fields than those used previously. The risk of provoking cardiac arrhythmias by these new devices is of concern. In the paper, the threshold for cardiac stimulation by an externally-applied magnetic field is determined for 11 anaesthetised dogs. Two coplanar coils provide the pulsed magnetic field. An average energy of approximately 12 kJ is required to achieve closed-chest magnetically induced ectopic beats in the 17-26 kg dogs. The mean peak induced electric field for threshold stimulation is 213 V m-1 for a 571 microseconds damped sine wave pulse. Accounting for waveform efficacy and extrapolating to long-duration pulses, a threshold induced electric field strength of approximately 30 V m-1 for the rectangular pulse is predicted. It is now possible to establish the margin of safety for devices that use pulsed magnetic fields and to design therapeutic devices employing magnetic fields to stimulate the heart.

Animals

Inhibition of protein synthesis in irradiated larvae of Schistosoma mansoni.

UV-irradiated and gamma-irradiated schistosomula of Schistosoma mansoni induce high levels of resistance to challenge infection in experimental hosts. It was observed that both types of irradiation severely inhibited protein synthesis by the parasite larvae. Schistosomula were treated with the metabolic inhibitor actinomycin D to simulate this effect of irradiation. The ability of these drug-treated larvae to induce immunity was tested in animal protection experiments. Our results suggest that inhibition of protein synthesis may help to generate the enhanced immunogenicity of irradiated schistosomula. In explanation, we propose that irradiated schistosomula may be such potent immunogens because they express antigens in disrupted, abnormal conformations. Inhibition of protein synthesis may both directly create such modified antigens, and also ensure that they persist and accumulate for presentation to the host immune system.

Animals

Association between surface electromyography of human jaw-closing muscle and quantified food breakdown.

Simultaneous recordings of the activity of the masseter and anterior temporalis and of jaw movement were made on 10 healthy dentate volunteers while they chewed roasted peanuts in their habitual manner. The quantity of food taken was altered by varying (a) its total weight (mouthful) between 8 and 1 g, but with a fixed initial particle size and (b) by varying its initial particle size between median sizes of 9.2 and 2.4 mm, but keeping the mouthful constant. Significant differences were found in the peak and mean (r.m.s.) estimates of muscle activity (particularly in the masseter), and the dimensions of jaw movements. These differences were associated with the variation in both the size of the mouthful and of the initial particles but were much greater with changes in the mouthful. A dimensional argument treating both the weight of food in the mouth and initial particle size as volumes showed that initial particle volume had been varied by approximately 50 times as much as mouthful volume and therefore that the mouthful was a far more critical factor in masticatory physiology than was the particle size of the food. The reasons for this probably lie in an understanding of mechanisms of food comminution.

Adult

Turgor-responsive gene transcription and RNA levels increase rapidly when pea shoots are wilted. Sequence and expression of three inducible genes.

Reduction of turgor in pea shoots caused the accumulation of several poly(A) RNAs. cDNA clones derived from three different poly(A) RNAs which accumulate in wilted pea shoots were isolated, sequenced and expression of the corresponding genes examined. Clone 7a encoded a 289 amino acid protein. The C-terminal 180 amino acids of this protein were homologous to soybean nodulin-26. RNA hybridizing to cDNA 7a was abundant in roots, and induced in shoots by dehydration, heat shock and to a small extent by ABA. Hydropathic plots indicate that the protein encoded by cDNA 7a contains six potential membrane spanning domains similar to proteins which form ion channels. Clone 15a encoded a 363 amino acid protein with high homology to cysteine proteases. RNA hybridizing to cDNA 15a was more abundant in roots than shoots of control plants. Dehydration of pea shoots induced cDNA 15a mRNA levels whereas heat shock or ABA treatment did not. Clone 26g encoded a 508 amino acid protein with 30% residue identity to several aldehyde dehydrogenases. RNA hybridizing to cDNA 26g was induced by dehydration of shoots but not roots and heat shock and ABA did not modulate RNA levels. Levels of the three poly(A) RNAs increased 4-6-fold by 4 h after wilting and this increase was not altered by pretreatment of shoots with cycloheximide. When wilted shoots were rehydrated, RNA hybridizing to cDNA 26g declined to pre-stress levels within 2 h. Run-on transcription experiments using nuclei from pea shoots showed that transcription of the genes which encode the three poly(A) RNAs was induced within 30 min following reduction of shoot turgor. One of the genes showed a further increase in transcription by 4 h after dehydration whereas transcription of the other 2 genes declined. These results indicate that plant cells respond to changes in cell turgor by rapidly increasing transcription of several genes. Furthermore, the expression of the turgor-responsive genes varies with respect to the time course of induction and reversibility of the wilting-induced changes.

Amino Acid Sequence

Sequence and transcriptional analysis of the barley ctDNA region upstream of psbD-psbC encoding trnK(UUU), rps16, trnQ(UUG), psbK, psbI, and trnS(GCU).

A 6.25 kbp barley plastid DNA region located between psbA and psbD-psbC were sequenced and RNAs produced from this DNA were analyzed. TrnK(UUU), rps16 and trnQ(UUG) were located upstream of psbA. These genes were transcribed from the same DNA strand as psbA and multiple RNAs hybridized to them. TrnK and rsp16 contained introns; a 504 amino acid open reading frame (ORF504) was located within the trnK intron. Between trnQ and psbD-psbC was a 2.24 kbp region encoding psbK, psbI and trnS(GCU). PsbK and psbI are encoded on the same DNA strand as psbD-psbC whereas trnS(GCU) is transcribed from the opposite strand. Two large RNAs accumulate in barley etioplasts which contain psbK, psbI, anti-sense trnS(GCU) and psbD-psbC sequences. Other RNAs encode psbK and psbI only, or psbK only. The divergent trnS(GCU) located upstream of psbD-psbC and a second divergent trnS(UGA) located downstream of psbD-psbC were both expressed. Furthermore, RNA complementary to psbK and psbI mRNA was detected, suggesting that transcription from divergent overlapping transcription units may modulate expression from this DNA region.

Amino Acid Sequence

Theoretical basis for controlling minimal tumor temperature during interstitial conductive heat therapy.

This paper describes simulation of steady-state intratumoral temperatures achieved by a simple modality of local heat therapy: interstitial treatment with parallel arrays of warmed, conductive heating elements. During "conductive heating" power is directly deposited only in the interstitial probes. Adjacent tissue is warmed by heat conduction. Simulations of interstitial conductive heating involved solution of the bioheat transfer equation on a digital computer using a finite difference model of the treated tissue. The simulations suggest that when the complete temperature distributions for conductive interstitial hyperthermia are examined in detail, substantial uniformity of the temperature distributions is evident. Except for a thin sleeve of tissue surrounding each heating element, a broad, flat central valley of temperature elevation is achieved, with a well defined minimum temperature, very close to modal and median tissue temperatures. Because probes are inserted directly in tumor tissue, the thin sleeve of overheated tissue would not be expected to cause normal tissue complications. The temperature of the heated probes must be continuously controlled and increased in the face of increased blood flow in order to maintain minimum tumor temperature. However, correction for changes in blood flow is possible by adjusting probe temperature according to a feedback control scheme, in which power dissipation from each probe is the sensed input variable. Conductive interstitial heating with continually controlled probe temperature deserves investigation as a technique for local hyperthermia therapy.

Computer Simulation

Schistosome fecundity: influence of host genotype and intensity of infection.

The host genetic influence on the fecundity of Schistosoma mansoni was studied by measuring egg excretion and accumulation of eggs in the tissues of two inbred strains of mice. The two strains, NIH/Ola and CBA/Ca, differed in both parameters. Egg excretion after infection in the NIH/Ola reached a maximum and declined earlier than was the case for the CBA/Ca mice. More eggs accumulated in the gut and lungs of CBA/Ca, while the NIH/Ola had more eggs in the liver by 100 days post-infection. Statistical analysis of both tissue eggs and faecal eggs, using a robust, non-parametric method, indicated that there is significant evidence for a density dependent reduction in fecundity of worms in more heavily infected animals. We conclude that both the genetic constitution of the murine host and the intensity of infection affect the fecundity of Schistosoma mansoni worms.

Animals

Establishing a system of complementary school-based surveys to annually assess HIV-related knowledge, beliefs, and behaviors among adolescents.

The Division of Adolescent and School Health, Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control has responsibility for assisting national, state, and local education agencies to provide effective HIV education for youth. In fall 1987, 14 state and 9 local education agencies that serve areas with the highest cumulative incidence of AIDS cases convened to develop a common set of data items that could provide comparable information about HIV-related knowledge, beliefs, and behaviors among adolescents in their respective jurisdictions over time. Surveys were administered during spring 1988 to representative samples of adolescents in each participating state and city. These education agencies will use the results from this complementary system of school-based surveys as a guide in planning HIV education, setting program priorities, allocating resources, and monitoring changes in HIV-related knowledge, beliefs, and behaviors among adolescents.

Acquired Immunodeficiency Syndrome

Variation in susceptibility of Schistosoma mansoni to damage by polycations.

We have studied the characteristics of binding of the polycation poly-L-lysine to the schistosome surface. Two consequences of this binding were measured: (a) tegumental damage, as assessed by the uptake of the DNA binding stain Hoechst 33258, and (b) the effect of cation binding on the uptake of a lipid analogue, 5-(N-octadecanoyl) aminofluorescein. Schistosomes were incubated with a preparation of eosinophil cationic proteins; these naturally occurring polycations bound to and damaged the parasites in a manner similar to poly-L-lysine. The different developmental stages of the parasite vary in the degree to which the poly-L-lysine binds, in susceptibility to tegumental damage, and in the degree to which lipid uptake is affected. The lung stage is most resistant to damage, and 3-week-old worms are the most susceptible. The teguments of male and female adult worms differ in the binding of the poly-L-lysine. Individual schistosomula, and batches of schistosomula shed at different times, show non-genetic variation in binding and susceptibility to damage. These findings may relate to variation in immune killing in vivo.

Animals

An in vivo model for the study of chemotaxis induced by schistosomula of Schistosoma mansoni.

Peritoneal leucocytosis, with an increased percentage of eosinophils, was found in mice which had been infected with Schistosoma mansoni for 7 weeks or longer. Specific IgG against worm and egg antigens increased in peritoneal fluids and their corresponding sera respectively 5 and 7 weeks after infection. An intraperitoneal challenge with schistosomula elicited neutrophilia in all mice regardless of immune status, as well as infiltration of eosinophils and macrophages in infected mice. The secondary eosinophilia occurred in mice previously infected for 1 week or longer, whereas the infiltration of macrophages occurred only after worms from the primary infection had started laying eggs. Unlike the eosinophilia the macrophage response required infection with bisexual populations of cercariae. Injection of previously infected mice with Escherichia, Trichinella or Toxocara failed to increase the proportions of eosinophils and macrophages. Schistosomula-induced eosinophilia could be elicited in passively sensitized mice. Intraperitoneal injection of PBS extract of adult worms elicited eosinophilia in infected mice and neutrophilia in normal mice. Two chromatographic fractions induced eosinophilia and the third only neutrophilia. The relevance of these observations to host response to S. mansoni infections is discussed.

Animals

Increased oviposition and growth in immature Biomphalaria glabrata after exposure to Schistosoma mansoni.

Biomphalaria glabrata snails are known to be castrated by infection with the trematode parasite Schistosoma mansoni 4-6 weeks post-infection. The pattern of oviposition in the first 35 days post-exposure (p.e.) was investigated, in snails aged 14 weeks and measuring 7-10 mm diameter which had not commenced egg-laying, by counting the numbers of eggs laid in 7-day intervals. A group of exposed snails was compared with a control non-exposed group. The exposed group included both parasitized and non-parasitized snails, and showed a significant increase in the median number of eggs laid during the periods 14-21 and 22-28 days p.e. Throughout the entire 35-day period exposed non-parasitized snails laid significantly more eggs than control snails, while parasitized snails laid significantly more eggs than controls during days 22-28 p.e. and significantly fewer during days 29-35 p.e. Parasitized snails also laid significantly more eggs/egg mass in the period 16-28 days p.e. than did control snails. Growth of the snails was measured. By day 28 p.e. the mean diameter of the exposed group was significantly greater than that of the control group. The increase in oviposition by snails soon after exposure is discussed in terms of a compensatory response for expected future suppression of egg-laying. The fact that parasitized and non-parasitized snails both show increased oviposition indicates that normal development of the parasite is not necessary to trigger the response.

Animals

The inheritance of responses to schistosomiasis mansoni in two pairs of inbred strains of mice.

Genetic differences in mice influence both the pathological and immunological responses to schistosomiasis mansoni. We have investigated the nature of the genetic factors influencing these responses by crossing two different pairs of strains of mice which vary in their response to infection, and measuring responses in the F1 hybrid and backcross offspring. The two pairs of parental strains differed with respect to faecal egg excretion, accumulation of eggs in the tissues, splenomegaly and pattern of antibody response. The numbers of adult worms which establish do not differ between strains. The inheritance of the responses measured was different in the two pairs of strains. The F1 hybrid from the C57BL/6/0la X BALB/c cross resembled the low-responding parental strain (C57BL/6/0la) with respect to faecal egg excretion, accumulation of eggs in the tissues and splenomegaly, and was intermediate in its pattern of antibody response. The F1 hybrid mice from the NIH X CBA/Ca cross resembled the high-responding strain (CBA/Ca) with respect to faecal egg excretion, accumulation of eggs in the tissues and splenomegaly, and had an earlier and greater antibody response than either parental strain. No evidence of single gene influence on any of these responses was seen in the backcross offspring. The differing patterns of inheritance and the absence of a bimodal distribution of responses in the backcross offspring indicate that each of these responses is influenced by multiple genes. The pattern of antibody response did not correlate between strains with any of the pathological responses. The positive correlation of egg accumulation in the tissues and faecal egg excretion suggests that there are genetic influences on the fecundity of the worms.

Animals

Lactate dehydrogenase C4 in male sex accessory glands of normal mice and in testes of sex-reversed mice.

Lactate dehydrogenase (LDH) C4 activity was observed in testis extracts of sex-reversed mice (Sxr) and in male sex accessory gland (seminal vesicle and prostate) extracts from C3H/He and C57BL/Go mice. These results reflect either (1) the presence of low concentrations of germinal cells in these tissues; or (2) the synthesis of LDH-C4 by somatic cells in Sxr testes and normal male sex accessory glands.

Alcohol Oxidoreductases

Electrophoretic analyses of lactate dehydrogenase C4 in testes and vesicular glands of normal and male sterile translocation mice.

Lactate dehydrogenase (LDH) C, activity was observed in testis extracts from normal mice but was progressively reduced in mice carrying the male-sterile translocations T31H, T32H, T37H, T38H, T40H and T42H, with no detectable activity being observed in the last two mice. None of the vesicular gland extracts from these male-steriles showed LDH-C4 activity, unlike normal mice. The differential LDH-C4 activity in male-sterile testes is interpreted as reflecting the varying stages of the spermatogenic defect during meiosis. In general, early meiotic defects exhibited no LDH-C4 activity whereas late stage (usually after metaphase-1 stage) defect animals exhibited some activity. The results also provide evidence for contaminating sperm being the source of normal vesicular gland LDH-C4 activity.

Animals