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Biomedical subjects

W James

Publications and source records attributed to W James.

16 recordsLinked to original sources
PubMed1991

Inhibition of heterologous strains of HIV by antisense RNA.

Antisense RNA can inhibit the expression of messenger RNAs (mRNAs) to which they are complementary by a variety of mechanisms and might provide the basis for antiviral therapies of high selectivity. In a previous study of six retrovirally expressed antisense RNAs targeted to HIV-1IIIB, we found that two significantly reduced HIV-1IIIB replication. Here we test the degree to which this inhibitory effect tolerates the natural variation found in the nucleotide sequence of different strains of HIV-1. We show that the longer of the two inhibitory antisense RNAs (600 bases) inhibits replication of HIV strains RF, MN and SF2 to at least as great an extent as it does the homologous strain. In contrast, the shorter (71 bases) does not inhibit replication of the heterologous strains. An examination of the predicted positions of the mismatches in the duplexes formed between the IIIB antisense RNAs and the mRNAs of heterologous strains suggests that one requirement of an inhibitory antisense RNA is that it can form a perfect duplex with its target mRNA of at least some 51-64 base-pairs. Although the observations presented here are not definitive proof of this, they are reminiscent of the structural requirements deduced for the double-stranded RNA-mediated induction of interferon and the activation of interferon-induced 2', 5'-oligo(A) synthetase and protein kinase. We tested the ability of antisense RNA to inhibit HIV replication in Jurkat, CEM, U937 and HeLa-T4 cells. The level of inhibition of HIV-1IIIB replication varied according to the cell line in which it was expressed, but in all cases was significant.

Animals↗
PubMed1991

Physicians promoting bicycle helmets for children: a randomized trial.

Head injury is the leading cause of death and serious morbidity in bicycle accidents. There is good evidence to recommend helmets, yet few children wear them. We evaluated helmet promotion in a randomized trial targeting children presenting to primary care settings for routine ambulatory care. The intervention consisted of physician counseling and take-home pamphlets. The study involved 339 families, 167 in the intervention group and 172 in the control group. In a follow-up telephone call, 2 to 3 weeks later, only 7.2% of the intervention group had purchased helmets, compared with 7.0% of the control group (chi 2 = 0.0056, P = .94). During the latter half of the study, bicycle safety received considerable media attention in Ottawa, and the provincial medical society sponsored a $5 discount campaign. Therefore both groups were subject to community "co-intervention." Nonetheless, we were surprised that physician counseling made no additional impact. Our results and the success of certain community programs suggest that physicians interested in helmet promotion would do better to participate in the design and implementation of multidisciplinary campaigns.

Adolescent↗
PubMed1990

Inhibition of human immunodeficiency virus replication in cell culture by endogenously synthesized antisense RNA.

Antisense RNA, which has a sequence complementary to mRNA, may provide the basis for antiviral therapies of high selectivity. We have explored the inhibitory effect of six antisense RNAs upon the replication of human immunodeficiency virus (HIV) in cell culture. We chose regions of the HIV genome to test whether sequences required for splicing or for translation initiation were more susceptible to antisense RNA interference. Our results suggest that inhibitory antisense RNAs contain sequences complementary to the AUG initiation codon of the tat gene and have a comparatively low tendency to form intramolecular base pairs which would interfere with intermolecular duplex formation. Inhibition can be substantial (over 70%) but is transient. Transience does not result from mutation of the input virus. Inhibition was not a consequence of the induction of interferon by antisense RNA-mRNA duplex formation. Our results suggest that at least part of the inhibitory effect is at the posttranscriptional level.

Base Sequence↗
PubMed1990

Autoantibodies from patients with localized and generalized bullous pemphigoid immunoprecipitate the same 230-kd keratinocyte antigen.

Two patients demonstrating the typical clinical, histologic, and immunopathologic features of nonscarring localized bullous pemphigoid are described. These patients possess circulating IgG autoantibodies that bind the epidermal side of 1.0-mol/L sodium chloride-split human skin in indirect immunofluorescence microscopy. Immunnoprecipitation studies demonstrate that these patients have circulating autoantibodies that immunoprecipitate the same 230-kd bullous pemphigoid antigen that is precipitated by autoantibodies from patients with generalized bullous pemphigoid. These findings indicate that localized bullous pemphigoid is a true clinical variant of generalized pemphigoid rather than a separate nosologic entity.

Aged↗
PubMed1989

Purified, modified eel sodium channels are active in planar bilayers in the absence of activating neurotoxins.

A recent study showed that limited trypsin treatment of liposomes containing purified Electrophorus electricus sodium channels activates a sodium radiotracer flux. We now report that similarly treated sodium channels show voltage-gated, tetrodotoxin-sensitive and highly sodium-selective single-channel currents when incorporated into planar lipid membranes. The trypsinized channels opened repeatedly in bursts of several seconds duration, as would be expected for channels whose fast inactivation process had been removed. Furthermore, they have a higher conductance, different voltage-dependence of gating, and a remarkably higher selectivity (PNa/PK = 41) than sodium channels bound by batrachotoxin or other activating neurotoxins; these properties of the trypsinized channels are probably closer to those of channels in intact electrocytes.

Animals↗
PubMed1976

Six unusual cases of drug overdose.

Six patients out of a total of 1,137 adults treated for drug overdose died during the period May, 1968 to June, 1973. Their case histories are summarized, and the conclusion drawn that, whilst death from drug overdose is unusual, increased vigilance particularly for the unsuspected secondary diagnosis or complication, is needed if there is to be any further reduction in the already small mortality rate.

Adult↗
PubMed1976

Grey-scale ultrasonic imaging of the kidney.

The ultrasonic appearances of the kidney in images which contain grey shades corresponding to the detected echo-pulse heights have been examined. These "greyscale" images were obtained using a standard Nuclear Enterprises Diasonograph 4102B and a Varian 620/L digital computer interfaced to this Diasonograph. The computer was used to analyse and display the ultrasonograms with 16 grey shades. Both kidneys of 36 subjects were examined and compared with IVU findings. This group included patients with normal kidneys, polycystic kidneys, hydronephrosis, glomerulonephritis and neoplastic tumours. It was found possible to make sharp, grey-shaded ultrasonograms which were very useful to the diagnostician. In particular, the grey shade of the renal parenchyma was used as a standard to compare other grey-shaded structures. Also the grey shading was useful in defining the renal pelvis in transverse scans and the renal poles in axial scan.

Glomerulonephritis↗
PubMed1975

A comparison of thermography, radioisotope scanning and clinical assessment of the knee joints in haemophilia.

Thermography, radioactive scanning and clinical assessment of the knee joints of a series of patients with haemophilia or Christmas disease have been performed. A positive correlation was found between the abnormalities of the thermograms, radioactive scans and the clinical signs in acute haemarthrosis, but not in chronic haemophilic joint disease nor in patients without clinical joint disease. No correlation between the thermograms, radioactive scans and the number of previous joint bleeds was shown. Thermography and radionuclide scanning provide rapid means of quantifying changes within the haemophilic joint and may be useful in assessing treatment of haemophilic haemarthrosis.

Adolescent↗
PubMedDate not supplied

Development of techniques to analyse the formation of HIV provirus in primary human macrophages.

The formation of provirus is an important early event in the life cycle of a retrovirus. We describe a system using PCR for the analysis of this process in primary human macrophages infected in vitro with HIV. We show that products of the first template switch can be detected within 8 h after infection at low multiplicity. The methods described provide a rapid assay of infection with HIV and can be applied in the investigation of a number of aspects of HIV replication in macrophages.

Base Sequence↗