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Biomedical subjects

D Jones

Publications and source records attributed to D Jones.

At least 379 records · Page 21Linked to original sources

Functional equivalence of verbal and spatial information in serial short-term memory.

Performance on a test of serial memory for the spatial position of a sequence of dots showed similarities to typical results from the serial recall of verbal material: a marked increase in error with increasing list length, a modest rise in error as retention interval increased, and bow-shaped serial position curves. This task was susceptible to interference from both a spatial task (rote tapping) and a verbal task (mouthed articulatory suppression) and also from the presence of irrelevant speech. Effects were comparable to those found with a serial verbal task that was generally similar in demand characteristics to the spatial task. As a generalization, disruption of the serial recall of visuospatial material was more marked if the interference conditions involved a changing sequence of actions or materials, but not if a single event (tap, mouthed utterance, or sound) was repeated.

Humans↗

Co-expression of native and introduced genes reveals cryptic regulation of HMG CoA reductase expression in Arabidopsis.

In eukaryotes, all isoprenoid compounds share a common precursor, mevalonic acid, whose synthesis is catalyzed by the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. As one step towards a better understanding of the role that this enzyme plays in coordinating isoprenoid biosynthesis in plants, Arabidopsis thaliana HMG CoA reductase was ectopically expressed in transgenic Arabidopsis plants. By using this molecular genetic approach, several novel and fundamental observations have been made regarding isoprenoid biosynthesis in Arabidopsis. First, it was demonstrated that the overexpression of authentic Arabidopsis HMG CoA reductase is not sufficient to alter the bulk synthesis and accumulation of the abundant end products of the plant isoprenoid pathway. Second, active transcription of the transgene appears to co-activate and deregulate expression of the native gene, resulting in a striking elevation of HMG CoA reductase mRNA levels. Finally, although very high levels of HMG CoA reductase mRNA were expressed in these transgenic plants, only modest increases in enzyme activity could be detected. Taken together, these data suggest that HMG CoA reductase expression is regulated at multiple levels in plants as well as animals, and they provide a foundation for elucidating the molecular mechanisms for mevalonate regulation in A. thaliana.

Arabidopsis↗

Caenorhabditis elegans UBC-1, a ubiquitin-conjugating enzyme homologous to yeast RAD6/UBC2, contains a novel carboxy-terminal extension that is conserved in nematodes.

The RAD6/UBC2 gene from Saccharomyces cerevisiae encodes a ubiquitin-conjugating enzyme involved in DNA repair, induced mutagenesis, and sporulation. Here we report the isolation and characterization of the Caenorhabditis elegans RAD6 homolog designated ubc-1. Ubc-1 encodes a 21.5-kD protein that shares considerable identity with RAD6 (66%) as well as with other RAD6 homologs, including Schizosaccharomyces pombe rhp6+ (70%), Drosophila melanogaster Dhr6 (83%), and the two human homologs HHR6A and HHR6B (84% and 83%, respectively). However, UBC-1 is distinct in being the only known RAD6 homolog, other than RAD6 itself, with a carboxy-terminal extension. Analysis of UBC-1 homologs from C. briggsae and Ascaris suum show that the presence of the carboxy-terminal extension is conserved in nematodes. When constitutively expressed from the yeast promoter ADH1, ubc-1 complements the DNA repair functions in a S. cerevisiae rad6 delta mutant. Surprisingly, ubc-1 fails to complement the sporulation function of RAD6, despite its possession of an acidic carboxy-terminal tail. C. elegans UBC-1 is capable of forming a thiol-ester bond with ubiquitin, but, unlike RAD6, is unable to transfer ubiquitin to histone H2B in vitro. Both cis and trans splicing are involved in the maturation of the ubc-1 transcript. The presence of the SL2 trans-splice leader in the ubc-1 transcript suggests that ubc-1 may be co-transcribed as part of a polycistronic message.

Amino Acid Sequence↗

Detailed mapping and loss of heterozygosity analysis suggests a suppressor locus involved in sporadic breast cancer within a distal region of chromosome band 17p13.3.

The chromosome region 17p13.3 is thought to encode a tumour suppressor gene involved in sporadic breast cancer and other malignancies. Physical ordering of markers has been carried out by a series of multicolour fluorescent in situ hybridisation (FISH) experiments, using isolated yeast artificial chromosomes (YACs) and cosmids. Eight polymorphic markers ordered within this new physical map and one external marker were used to investigate the pattern of loss of heterozygosity in a panel of 40 sporadic breast tumour patients. The data revealed a region of high loss (60%) within distal 17p13.3, defined by markers D17S926, D17S695 and D17S849 which mapped close together. A contig of YACs was constructed physically linking these three markers.

Base Sequence↗

Phase II trial of isotretinoin and recombinant interferon alfa-2a in metastatic colorectal carcinoma.

Phase II trials of the novel biologic combination isotretinoin (13-cis-retinoic aid) plus recombinant interferon alfa-2a have demonstrated this combination's major activity against advanced squamous cell carcinoma of the skin and cervix. Because this combination has had limited study in other tumors, we initiated a phase II trial of this regimen in patients with metastatic colorectal adenocarcinoma. Sixteen patients with measurable metastatic colon carcinoma who had received no previous chemotherapy were entered on the trial. Patients received recombinant interferon alfa-2a, 6 million units a day subcutaneously, and isotretinoin, 1 mg/kg per day orally in two divided doses. Patients were evaluated for response after 8 weeks of treatment and then continued on therapy until progressive disease was documented. We did not observe complete or partial responses. Two patients experienced minor responses in measurable pulmonary metastases lasting 12 and 8 weeks. Grade 3-4 toxic reactions included fatigue (5 patients), granulocytopenia (6 patients), neurotoxicity (2 patients), and elevated serum triglyceride levels (2 patients). Although this combination has demonstrated significant activity in squamous cell carcinomas of the skin and cervix, our results suggest that it has little therapeutic activity against advanced colorectal adenocarcinomas.

Adenocarcinoma↗

Pilot phase II trial of 13-cis-retinoic acid and interferon-alpha combination therapy for advanced pancreatic adenocarcinoma.

The combination of interferons (IFNs) and retinoids in antineoplastic therapy is based upon preclinical, in vitro, and in vivo observations. Retinoid-IFN combinations have shown significant antitumor activity against advanced cutaneous and cervical squamous cell carcinoma (SCC), and the toxic effects do not appear to overlap. Based on in vitro evidence of synergy and observed clinical activity, we conducted a pilot phase II trial of 13-cis-retinoic acid (1 mg/kg/day) and IFN alpha (6 million units/day) in patients with advanced pancreatic adenocarcinoma. No objective responses occurred among six evaluable patients. The toxicities were mild and reversible, and grade 3 fatigue occurred in only one patient. No objective antitumor activity was noted against pancreatic adenocarcinomas at the dose and schedule utilized. Further exploration of this this purely biological approach is not warranted for pancreatic adenocarcinomas.

Adenocarcinoma↗

Moclobemide in chronic neuropathic pain: preliminary case reports.

OBJECTIVE: This trial aimed to study moclobemide, a reversible, Type-A selective monoamine oxidase inhibitor, in patients with chronic neuropathic pain. DESIGN: Pain clinic patients suitable for antidepressant therapy were treated for 2 months in an open label, uncontrolled trial with moclobemide 150-600 mg/day. OUTCOME MEASURES: Visual analog scores of pain and affective symptoms, a side-effect checklist, and clinical global impressions of efficacy and tolerability. RESULTS: The trial was terminated after assessment of seven patients; partial analgesic activity was discernible only in one, and beneficial mood effects notable in two others. Significant adverse effects, particularly insomnia and GI disturbance, were reported by the majority of patients. CONCLUSION: Moclobemide appears to have limited efficacy in the treatment of neuropathic pain.

Adult↗

Predicting the one-year course of adolescent major depression.

OBJECTIVE: To identify specific clinical and social functioning variables that predict persistence of major depression over a 1-year period of follow-up. METHOD: The sample consisted of 67 adolescents with major depression, drawn from consecutive referrals to psychiatric clinics in a defined, geographic catchment area. Clinical interviews and questionnaires measuring behaviors, symptoms, and social functioning were administered to both the adolescent and a parent at inception and at follow-up. Discriminant function analyses were used to identify inception variables that predicted clinical course independent of severity of depressive symptoms and global functioning. RESULTS: At 1-year follow-up, major depression remitted in 66% of subjects. Persisters were characterized at inception as older, more likely to have substance use or anxiety disorders, less involved with fathers, and less responsive to mother's discipline compared with remitters. The effect of these prognostic factors was independent of symptom severity and global functioning. CONCLUSION: These variables appear to reflect perpetuating and ameliorating factors influencing the short-term course of major depression. The findings suggest that treatments for adolescent depression that aim to enhance parent-adolescent relationships, and that specifically target coexisting disorders, should be evaluated for effectiveness.

Adolescent↗

Effects of the cholinomimetic SDZ ENS-163 on scopolamine-induced cognitive impairment in humans.

Scopolamine-induced cognitive impairment was used in healthy men to evaluate the central nervous system activity of the new cholinomimetic SDZ ENS-163. Eighteen subjects were treated in a crossover design with oral placebo/intravenous saline, 50 mg of oral SDZ ENS-163/intravenous saline, oral placebo/0.4 mg of intravenous scopolamine, and 50 mg of oral SDZ ENS-163/0.4 mg of intravenous scopolamine. The administration of placebo with scopolamine caused significant cognitive impairment, as assessed by the Computerized Neuropsychological Test Battery (CNTB), and also decreased salivation and heart rate. In contrast, SDZ ENS-163 with saline had no effect on CNTB scores, increased salivation, and increased heart rate. Despite the observed cholinomimetic effects of SDZ ENS-163 when administered with saline, the changes in CNTB scores, heart rate, and salivation were indistinguishable between placebo/scopolamine and SDZ ENS-163/scopolamine. Thus, 50 mg of oral SDZ ENS-163 has cholinomimetic activity in normal men, but this dose is insufficient to reverse the muscarinic effects of 0.4 mg of intravenous scopolamine.

Adult↗

A comparison of malreduction after plate and intramedullary nail fixation of forearm fractures.

A study was performed to compare the degree of malreduction after intramedullary nail and plate fixation of the forearm and to determine if the degree of malreduction was clinically significant. Eight matched pairs of forearms, including the wrist and elbow joints, were harvested from cadaver upper extremities. The forearms were put through a full range of motion, and physiological loads were applied to simulate those during normal use. Standardized anteroposterior and lateral radiographs of each forearm were obtained with the specimen intact, and after an osteotomy and internal fixation of one bone, both bones, and with gap at the osteotomy sites. In each forearm pair, plating was randomly performed in one specimen and intramedullary nailing was performed in the matching contralateral specimen. Forearm architecture was assessed by quantification of the magnitude and location of maximum radial bow and radial angulation. In this study, plate fixation was superior to nail stabilization in restoration of the normal radial architecture. Plating did not change any of the radiographic indices (magnitude and location of maximum radial bow and radial angulation) at any stage of testing. None of the radiographic indices was changed by nailing of only one of the forearm bones. The magnitude of maximum radial bow and the radial angulation were changed by nailing both forearm bones after osteotomy and both forearm bones with a gap (p < 0.05). Despite this, both techniques were well within the limits of what is radiographically acceptable for reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Nails↗

The analysis of censored treatment cost data in economic evaluation.

This article investigates the way in which the presence of censored cost data in clinical trials should dictate the inferential tests adopted when comparing treatment and nontreatment groups for the purpose of economic evaluation. The authors argue that the techniques of survival analysis are appropriate where censoring is present, and that bias will be imparted if cruder methods are used to analyze cost data, even if that data is drawn from a relevant population. The first section of the article discusses the problem of censoring and survival analysis, while the second examines three methods of dealing with censored cost data and possible biases resulting from them. The third section presents results from actual trial data using the three methods described in the preceding section. Conclusions are presented in section four, where it is argued that these methodological issues are likely to become more important as economists are called upon to evaluate the treatment of chronic conditions using data from clinical trials with finite end points.

Bias↗

Clinical results of pharyngeal flap surgery: the Iowa experience.

Sixty-five patients with cleft palate, with or without cleft lip, who received previous pharyngeal flap surgery for chronic velopharyngeal dysfunction in our department, were examined for velopharyngeal status, speech production patterns, and evidence of nasal airway obstruction. Of the 65 subjects, 54 (83.1 percent) showed velopharyngeal function within normal limits, 43 (66.1 percent) showed normal or near-normal speech production, and 58 (89.2 percent) reported snoring sometimes or often. Of the 58 reporting snoring, electrocardiogram (ECG) data for 33 were examined for evidence of right ventricular hypertrophy. Only one (3 percent) of the 33 showed such possible indication. We conclude that by our methods, pharyngeal flap surgery is an effective treatment for velopharyngeal dysfunction. After surgery, patients may report symptoms of nasal airway obstruction during sleep but are not expected to show ECG changes in cardiac function resulting from oxygen deprivation.

Adolescent↗

Comparative study of the growth of Listeria monocytogenes in defined media and demonstration of growth in continuous culture.

A basic requirement for physiological studies with Listeria monocytogenes is a chemically defined medium that supports growth of the bacterium in batch and continuous culture. A number of such media have been devised but comparative studies of their efficiency are few and none has been used in continuous culture. Six of the media were compared for their ability to sustain sequential growth of L. monocytogenes in static and aerated batch culture with glucose as sole carbon source. The most suitable, judged on the basis of ease of preparation, growth rate and yield, was that of Trivett and Meyer (1971). This medium was shown to support growth of L. monocytogenes NCTC 7973 in continuous culture in a chemostat. A lytic phenomenon, noted with the same strain under anaerobic conditions and in batch culture in the chemostat, is discussed.

Aerobiosis↗

Phenotypic and phylogenetic characterization of some unknown coryneform bacteria isolated from bovine blood and milk: description of Sanguibacter gen.nov.

16S rRNA gene sequencing studies were performed on some Gram-positive coryneform bacteria of unknown taxonomic position isolated from blood and milk of healthy cows. Comparative sequence analysis demonstrated that the milk isolates corresponded to Oerskovia xanthineolytica whereas those from blood consisted of two distinct, albeit highly related species, within the family Cellulomonadaceae. Based on the phylogenetic and phenotypic distinctiveness of the blood isolates, it is proposed that they be classified in a new genus Sanguibacter.

Actinomycetales↗

The Q-switched Alexandrite laser's effects on tattoos in guinea pigs and harvested human skin.

BACKGROUND: Developmental work in tattoo removal is currently carried out in animal models whose skin has different optical and mechanical properties from human skin. OBJECTIVE: To observe laser effects on tattoos in a new human skin model and that of in vivo guinea pig skin. METHODS: A comparison of the efficacy of the Q-switched Alexandrite laser (750 nm, 100-120 nanoseconds) in tattooed harvested human skin and guinea pig skin was performed. Visual assessments as well as histologic and electron microscopy evaluation before and after treatment are reported. RESULTS: Mild to moderate clearing of black tattoo pigment, as judged by visual assessment, was found after one laser treatment in both the in vitro human skin model and guinea pig skin. Blue and green ink showed similar results to black ink in human skin whereas red and yellow ink did not respond in our model. CONCLUSION: Possible mechanisms of tattoo lightening and the usefulness of the in vitro human skin model are discussed.

Animals↗