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Biomedical subjects

D Jones

Publications and source records attributed to D Jones.

At least 253 records · Page 14Linked to original sources

Self-reported delinquent behavior and psychosocial functioning in inner-city teenagers: a brief report.

Evaluated psychosocial characteristics of inner-city ninth graders exceeding a cutoff for clinically significant delinquent behaviors (n = 27), as compared to youth whose self-reported delinquent behaviors fell below this cutoff (n = 136). Youth reporting high levels of delinquent behavior reported more life stress, depression and anxiety, lower self-concept, and less cohesive families than other students. Females reporting high levels of delinquent behavior were more likely to have poor classroom and school attendance than other females; this relationship did not hold for males.

Adolescent↗

Differentiation and reversal of malignant changes in colon cancer through PPARgamma.

PPARgamma is a nuclear receptor that has a dominant regulatory role in differentiation of cells of the adipose lineage, and has recently been shown to be expressed in the colon. We show here that PPARgamma is expressed at high levels in both well- and poorly-differentiated adenocarcinomas, in normal colonic mucosa and in human colon cancer cell lines. Ligand activation of this receptor in colon cancer cells causes a considerable reduction in linear and clonogenic growth, increased expression of carcinoembryonic antigen and the reversal of many gene expression events specifically associated with colon cancer. Transplantable tumors derived from human colon cancer cells show a significant reduction of growth when mice are treated with troglitazone, a PPARgamma ligand. These results indicate that the growth and differentiation of colon cancer cells can be modulated through PPARgamma.

Adenocarcinoma↗

Association and clonal distribution of trisomy 12 and 13q14 deletions in chronic lymphocytic leukaemia.

The coexistence of trisomy 12 and deletions of chromosome 13 (13q12-q32) has rarely been observed in chronic lymphocytic leukaemia (CLL). Fluorescence in situ hybridization (FISH) performed on 600 consecutive CLL patients revealed the association of trisomy 12 and 13q14 deletion, of at least one of the three markers analysed (RB1, D13S319 and D13S25), in 55 cases (9% of 600 and 46% of 120 trisomy 12 cases). Trisomy 12 and isolated RB1 deletion were seen in 14/120 cases, trisomy 12 and D13S319/D13S25 deletion with diploid RB1 in 19/118, and trisomy 12 and deletion encompassing the three 13q markers studied in 22/118 cases. The heterogenous distribution of trisomy 12 and 13q deletions within the neoplastic B cells suggests that they are secondary rather than primary events in CLL leukaemogenesis.

Chromosome Deletion↗

Classical conditioning modifies cytochrome oxidase activity in the auditory system.

The effects of excitatory classical conditioning on cytochrome oxidase activity in the central auditory system were investigated using quantitative histochemistry. Rats in the conditioned group were trained with consistent pairings of a compound conditional stimulus (a tone and a light) with a mild footshock, to elicit conditioned suppression of drinking. Rats in the pseudorandom group were exposed to pseudorandom presentations of the same tone, light and shock stimuli without consistent pairings. Untrained rats in a naive group did not receive presentations of the experimental stimuli. The findings demonstrated that auditory fear conditioning modifies the metabolic neuronal responses of the auditory system, supporting the hypothesis that sensory neurons are responsive to behavioural stimulus properties acquired by learning. There was a clear distinction between thalamocortical and lower divisions of the auditory system based on the differences in metabolic activity evoked by classical conditioning, which lead to an overt learned behavioural response versus pseudorandom stimulus presentations, which lead to behavioural habituation. Increases in cytochrome oxidase activity indicated that tone processing is enhanced during associative conditioning at upper auditory structures (medial geniculate nucleus and secondary auditory cortices). In contrast, metabolic activation of lower auditory structures (cochlear nuclei and inferior colliculus) in response to the pseudorandom presentation of the experimental stimuli suggest that these areas may be activated during habituation to tone stimuli. Together these findings show that mapping the metabolic activity of cytochrome oxidase with quantitative histochemistry can be successfully used to map regional long-lasting effects of learning on brain systems.

Acoustic Stimulation↗

History of the Kolff Laboratory turbine driven electrohydraulic artificial heart.

The concept of an electrically powered total artificial heart has been pursued by Dr. Kolff and his associates since the 1960s. Since the 1980s these efforts have been concentrated upon the development of the electrohydraulic total artificial heart, a turbine pump powered by a brushless DC motor. Dr. Kolff realized the benefits of pulsatile flow and device response to Starling's Law, and these concepts have formed the basis of subsequent design decisions. Design iterations have both solved existing problems and exposed new challenges. The current device design is greatly improved over early attempts due to the incorporation of technologies that have recently become available as the result of progress in the fields of materials and electronics and due to the lessons learned over many years of research under the guidance of Dr. Kolff. This article describes, from its inception, the last major research project of Dr. Kolff prior to his retirement. The discussion centers around development, problems and their solutions, and the reasoning for given solutions.

Animals↗

Characteristic proliferations of reticular and dendritic cells in angioimmunoblastic lymphoma.

Angioimmunoblastic lymphoma (AIL) is a T-cell proliferation with a distinct clinical presentation that often poses a difficult diagnostic challenge. Angioimmunoblastic lymphoma is characterized by prominent vascular and stromal proliferations. Using a panel of antibodies, we investigated the nature of the stromal component in 15 cases of AIL as compared with 40 cases of nodal-based peripheral T-cell lymphoma (PTCL) of other types. As has been previously noted, extrafollicular proliferations of follicular dendritic cells (detected by CD21 and low molecular-weight nerve growth factor receptor staining) were highly associated with AIL and were only rarely seen in other lesions. Unexpectedly, large networks of desmin-positive reticulum cells also were noted in all cases of AIL evaluated. These cells with characteristic long cytoplasmic processes were present in much smaller numbers or only rarely in other types of peripheral T-cell lymphoma. This population of nodal stromal cells, a subset of the fibroblastic reticulum cells detected by vimentin immunostaining, may be responsible for the prominent reticulum deposition seen in AIL. No association of AIL with proliferations of other types of reticulum cells (e.g., interdigitating dendritic cells or histiocytes) was noted. These findings suggest that networks of follicular dendritic and desmin-positive reticulum cells are useful diagnostic features in angioimmunoblastic lymphoma and probably are related to the pathogenesis of this entity.

Adult↗

The chemical stability and sterility of sodium thiopental after preparation.

UNLABELLED: Manufacturer's instructions recommend discarding unused portions of sodium thiopental 24 h after reconstitution. Heeding this recommendation may result in the disposal of a large proportion of prepared thiopental. Although thiopental is relatively inexpensive, the volume prepared by many anesthesia departments could make this waste significant. To address this possibility, we investigated the chemical stability and sterility of thiopental in pharmacy-prepared, prefilled syringes. Stock solutions of thiopental were mixed and drawn into syringes under sterile conditions by pharmacists or pharmacy assistants. Fifty-six samples were stored under refrigeration (3 degrees C); the remaining 56 samples were stored at room temperature (22 degrees C). Each day for 7 days, eight samples from each group were analyzed by using high-performance liquid chromatography for chemical stability and cultured for microbiological colonization. Differences in thiopental concentration between the room temperature and the refrigerated samples were measured over time by using repeated-measures analysis of variance (P < or = 0.05). Three positive culture samples (S. epidermidis and S. hemolyticus) most likely represent laboratory contamination and not colonization. At 22 degrees C, thiopental remains stable and sterile for 6 days and well beyond 7 days at 3 degrees C. IMPLICATIONS: This study examines the shelf life of the anesthetic drug thiopental in pharmacy-filled syringes stored at either room temperature or under refrigeration. The results justify the use of prepared solutions beyond the package insert recommendation of 24 h.

Anesthetics, Intravenous↗

The effect of auditory feedback on the control of oral-nasal balance by pediatric cochlear implant users.

OBJECTIVE: This study examined the control of oral-nasal balance by pediatric cochlear implant (CI) users, with and without auditory feedback. DESIGN: Five CI users read lists of sentences in two conditions: with their devices on and with their devices off. Their oral-nasal balance (ratio of energy radiated from the oral and nasal cavities) was measured in both conditions and compared with values obtained from children with normal hearing. RESULTS: CI users showed different patterns of abnormal oral-nasal balance with their devices off, but they generally achieved values that were closer to normal when their devices were on. CONCLUSIONS: The results suggest that children with CIs use the auditory signal provided by their device to improve their control of nasalization. It is also possible that at least part of the changes in oral-nasal balance were driven by changes in related articulatory parameters.

Adolescent↗

Provision of external cues and movement sequencing in Parkinson's disease.

The basal ganglia (BG) may play a part in motor sequencing. Individuals with Parkinson's disease (PD) may exhibit progressive slowing (sequence effect) during motor sequences such as writing (micrographia) and gait. In the present study, a serial two-way choice reaction time (CRT) task was employed, in which advance information about each next movement was not provided until the participant began moving, thereby assessing the participant's ability to utilize advance information. Participants were 13 individuals with idiopathic PD and 13 age-matched controls. Both PD subjects and controls showed a significant sequence effect in the absence of advance information, possibly reflecting difficulty in initiating and maintaining movement without external cues. PD subjects and controls both exhibited a sequence effect at moderate levels of advance information. At high levels of advance information, PD subjects showed the effect but controls did not, suggesting that controls, unlike PD subjects, were able to use the extra information to facilitate performance, perhaps reflecting more frontal aspects of impairment in PD.

Adult↗

Differential regulation of the interleukin-12 receptor during the innate immune response to Leishmania major.

Previous studies have shown the central role of interleukin 12 (IL-12) in the development of resistance to Leishmania major infection in C3H mice. We now show that during the innate immune response the lymph node cells of L. major-infected C3H mice upregulate the IL-12 receptor on CD4(+), CD8(+), and B220(+) cells. An increase in the ability of the lymph node cells to bind IL-12 correlates with 9.3- and 4.6-fold increases in the mRNA expression levels of the IL-12Rbeta1 and -beta2 subunits, respectively. In contrast, BALB/c mice, which are susceptible to L. major infection, have no increase in the ability of the lymph node cells to bind IL-12 and correspondingly smaller increases in the mRNA expression levels of the IL-12Rbeta1 and -beta2 subunits of 2- and 1.5-fold, respectively. Neutralizing IL-4 and the administration of exogenous IL-12 upregulate IL-12R expression in BALB/c mice, while the neutralization of IL-12 in C3H mice blocks increased IL-12 receptor expression. These experiments reveal an important role for the regulation of the IL-12 receptor during the innate immune response after infection of mice with a pathogen.

Animals↗

Quantification of alterations in structure and function of elastin in the arterial media.

The structure of medial elastin determines arterial function and affects wall mechanical properties. The aim of this study was to (1) characterize the structure of elastin in terms of textural features, (2) relate structural parameters to total number of cardiac cycles (TC), and (3) determine the contribution of medial elastin to lumen mechanical stress. Images of pressure-fixed aortic sections stained for elastin were obtained from specimens collected postmortem from 35 animals of different species with a wide range of age, heart rate, and TC and divided into 2 groups: TClow=3.69+/-0.38x10(8) (n=17) and TChigh=15.8+/-2.38x10(8) (n=18) (P<0.001). A directional fractal curve was generated for each image, and image texture was characterized by directional fractal curve parameters. Elastin volume fraction and interlamellar distance were obtained by image analysis. Wall stress distribution was determined from a finite element model of the arterial wall with multiple layers simulating elastin lamellae. DFC amplitude was related to elastin volume fraction. Increased TC (TClow versus TChigh) was associated with lower directional fractal curve amplitude (0.23+/-0.02 versus 0.14+/-0.02; P<0.001), reduced elastin volume fraction (36.5+2.6% versus 25.7+2.1%; P<0.01), and increased interlamellar distance (8.5+/-0.5 versus 11.5+/-1.0 microm; P<0.05). Loss of medial elastic function increased pressure-dependent maximal circumferential stress. Structural alterations of medial elastin, quantified by fractal parameters, are associated with cumulative effects of repeated pulsations due to the combined contribution of age and heart rate. Loss of medial functional elasticity increases luminal wall stress, increasing the possibility of endothelial damage and predisposition to atherosclerosis.

Age Factors↗

Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus.

Until recently it was thought that age greater than 35 yr was the main risk factor for the development of drug-induced hepatitis (DIH) in patients receiving antituberculosis therapy. We conducted a study to determine whether infection with either the hepatitis C virus or the human immunodeficiency virus (HIV) were significant risk factors for the development of DIH in patients receiving antituberculosis therapy. Our study consisted of two parts. In the first part, 134 consecutive patients admitted for the treatment of tuberculosis (TB) were followed for the development of DIH. All of these patients were also screened for the presence of hepatitis C and HIV. In the second part of the study, those patients who were hepatitis C positive and who developed DIH on repeated reintroduction of the anti-TB drugs were offered a liver biopsy. If active inflammation, which may be suggestive of hepatitis C infection, was present on the biopsy specimen, treatment with alpha-interferon was begun and the anti-TB drugs were subsequently reintroduced. During the 18 mo of the study, 22 patients developed DIH. The relative risk of developing DIH if the patient was hepatitis C or HIV positive was fivefold and fourfold, respectively (p < 0.05). If a patient was coinfected with both hepatitis C and HIV the relative risk of developing DIH was increased 14.4-fold (p < 0.002). In the treatment part, four patients were treated with alpha-interferon, and all were able to undergo the reintroduction of anti-TB therapy without reoccurrence of DIH. Infection with hepatitis C and HIV are independent and additive risk factors for the development of DIH during TB therapy. The treatment of hepatitis C with alpha-interferon may allow the reintroduction of anti-TB agents in those who previously developed DIH when exposed to these drugs.

Adolescent↗

Blood volume, plasma volume and circulation time in a high-energy-demand teleost, the yellowfin tuna (Thunnus albacares)

We measured red cell space with 51Cr-labeled red blood cells, and dextran space with 500 kDa fluorescein-isothiocyanate-labeled dextran (FITC-dextran), in two groups of yellowfin tuna (Thunnus albacares). Red cell space was 13.8+/-0.7 ml kg-1 (mean +/- s.e.m.) Assuming a whole-body hematocrit equal to the hematocrit measured at the ventral aortic sampling site and no significant sequestering of 51Cr-labeled red blood cells by the spleen, blood volume was 46. 7+/-2.2 ml kg-1. This is within the range reported for most other teleosts (30-70 ml kg-1), but well below that previously reported for albacore (Thunnus alalunga, 82-197 ml kg-1). Plasma volume within the primary circulatory system (calculated from the 51Cr-labeled red blood cell data) was 32.9+/-2.3 ml kg-1. Dextran space was 37.0+/-3.7 ml kg-1. Because 500 kDa FITC-dextran appeared to remain within the vascular space, these data imply that the volume of the secondary circulatory system of yellowfin tuna is small, and its exact volume is not measurable by our methods. Although blood volume is not exceptional, circulation time (blood volume/cardiac output) is clearly shorter in yellowfin tuna than in other active teleosts. In a 1 kg yellowfin tuna, circulation time is approximately 0.4 min (47 ml kg-1/115 ml min-1 kg-1) compared with 1. 3 min (46 ml kg-1/35 ml min-1 kg-1) in yellowtail (Seriola quinqueradiata) and 1.9 min (35 ml kg-1/18 ml min-1 kg-1) in rainbow trout (Oncorhynchus mykiss). In air-breathing vertebrates, high metabolic rates are necessarily correlated with short circulation times. Our data are the first to imply that a similar relationship occurs in fishes.

Journal Article↗

Good clinical practice and audits for dual X-ray absorptiometry and X-ray imaging laboratories and quality assurance centers involved in clinical drug trials, private practice, and research.

Good Clinical Practice (GCP) guidelines, with an emphasis on quality and validation of processes and data, must be applied to the use of imaging in clinical drug development. All participants, including the sponsor, principal investigator, site staff, quality assurance centers, and contract research organizations, must be cognizant of the need for application of these principles to their activities related to the imaging programs. This article discusses the various aspects of GCP as they need to be applied to the use of dual X-ray absorptiometry (DXA) for bone densitometry and X-rays for vertebral fracture assessment in clinical trials for osteoporosis, as well as research and private practice settings. The theory of proper audit conduct to verify clinical trial data is presented.

Journal Article↗