Liposomes as agents of DNA transfer.
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Animals↗
Biomedical subjects
J G Smith
Publications and source records attributed to J G Smith.
Histone octamer dissociation is not required for transcript elongation through arrays of nucleosome cores by phage T7 RNA polymerase in vitro.
We have examined whether dissociation of the histone octamer is required for elongation of RNA transcripts through arrays of nucleosome cores in vitro. Control or dimethyl suberimidate-crosslinked histone octamers were reconstituted onto supercoiled, closed circular pT207-18 DNA, which contains tandemly repeated 207-base-pair (bp) 5S rDNA nucleosome positioning sequences inserted between the T7 and SP6 transcription promoters of pGEM-3Z. Double label transcription experiments showed that there was little or no effect of extensive crosslinking of the histone octamers on transcription initiation and elongation by T7 RNA polymerase in vitro. Continuous regularly spaced linear arrays of either crosslinked or control nucleosome cores were obtained by digesting reconstituted nucleosomal pT207-18 templates with Dra I, a site that is protected from digestion by the presence of positioned nucleosome cores in the 207-pb sequence. After in vitro transcription with T7 RNA polymerase, an RNA ladder with 207-nucleotide spacing was obtained from templates reconstituted both with crosslinked and with control histone octamers, demonstrating clearly that neither partial nor complete dissociation of the histone octamer is essential for transcription elongation through arrays of nucleosome cores in vitro.
DNA-Directed RNA Polymerases↗
Contemporary management of adult and pediatric brain stem gliomas.
The aim of this study was to analyze the survival of a series of patients diagnosed as having brain stem tumors by computerized tomography scan, magnetic resonance imaging and/or biopsy and treated with megavoltage irradiation. Fifty-three patients presenting to the Peter MacCallum Cancer Institute with a diagnosis of brain stem tumor from January 1980 to July 1989 were reviewed. There were 32 pediatric (age < or = 16) and 21 adult patients. The median age at presentation was 12 years (range 2-73 years). Eighteen patients had biopsy proof of glioma, the rest were diagnosed on the basis of CT and/or MRI appearance. Eighty-seven percent of patients received 44-55 Gy in 1.67-2.25 Gy fractions to the brain stem. Seventy-seven percent of patients showed improvement following treatment, 6% were stable, 11% progressed, and 6% were not evaluable. The estimated median survival from presentation for all patients was 34 months with 49% surviving at 3 years. The estimated median time to progression was 19 months with 34% not progressed at 3 years. There was no significant survival difference between patients with biopsy-proven glioma and those patients where the diagnosis was made radiologically. Survival was not significantly affected by age-group or sex. Patients with symptoms for more than 9 months prior to presentation had significantly longer survival than those with shorter duration of symptoms (p = 0.002). This paper presents the survival of patients with brain stem tumors diagnosed and treated by contemporary radiological and radiotherapeutic techniques.
Adolescent↗
Bilateral basal cell carcinoma of the breasts.
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Aged↗
The effect of danazol on tumour control and weight loss in patients on tamoxifen therapy for advanced breast cancer: a randomised double-blind placebo controlled trial.
To assess the effect of danazol in advanced breast cancer 183 patients were randomised to receive either tamoxifen plus danazol or tamoxifen plus placebo. Patients underwent systemic work-up pretreatment then every 12 weeks or sooner if they clinically progressed. There were no differences in objective response rates with tamoxifen plus danazol vs. tamoxifen plus placebo (27% vs. 24%), time to progression (median 6.4 vs. 6.2 months) or survival (median 22.6 vs. 23.5 months) when the two arms were compared (all P > 0.5). The addition of danazol to tamoxifen had no effect on time to progression when adjusted for significant prognostic factors in a multivariate analysis. However, it was found incidentally that weight was stable on tamoxifen plus danazol (average gain 0.6 kg, S.E. 0.6 kg) compared with a significant loss on tamoxifen plus placebo (average loss 2.0 kg, S.E. 0.6 kg, P = 0.003). The average weight was maintained on tamoxifen plus danazol even in patients who did not respond to treatment.
Antineoplastic Combined Chemotherapy Protocols↗
Induction of tumor necrosis factor-alpha in murine Candida albicans infection.
Candidemia in humans is often associated with an endotoxic shock-like syndrome, comparable to gram-negative sepsis. Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator in the endotoxic shock syndrome. The possible role of TNF alpha causing early deaths was explored in a murine model of acute infection with Candida albicans. In vitro data from three mouse strains (BALB/c, C3H/HeJ, and C3H/HeN) and in vivo data from BALB/c mice were obtained. Peritoneal macrophages from all three strains produced TNF alpha in vitro when stimulated with C. albicans. After intravenous infection with 10(8) cfu of C. albicans, mice died within 12 h. TNF concentrations in sera from these mice were significantly greater than in controls. Pretreatment of BALB/c mice with anti-murine TNF alpha did not alter mortality of C. albicans-infected mice, but pretreatment with murine TNF alpha reduced mortality. Therefore, in contrast to what was anticipated, TNF alpha may serve a protective role in murine candidiasis.
Acute Disease↗
Etiology of venous ulceration.
The etiology of venous ulceration is far more complex than Homans' theory of stagnation and hypo-oxygenation. Indeed, studies have shown that flow in lipodermatosclerotic limbs is actually faster than normal. We suggest, therefore, that the terms "stasis dermatitis" and "stasis ulcer" be dropped from medical parlance. The term "lipodermatosclerosis with ulceration" as used by the British, or simply "venous ulcer," would seem more appropriate. Venous hypertension, produced by incompetence of deep and communicating vein valves and thrombosis of segments of the deep system, is closely correlated with the development of venous ulcers. Precisely how this venous hypertension translates into ulceration is unclear. Burnand et al showed that fibrin cuffs are deposited around the capillaries in lipodermatosclerotic limbs. These cuffs may serve as barriers to the diffusion of oxygen, leading to local ischemia and epidermal necrosis. Others suggest that trapped leukocytes in the microcirculation alter capillary permeability by releasing various inflammatory mediators that hasten the flow of fibrinogen across the capillary membrane and promote the formation of fibrin cuffs. Proof of this hypothesis is still lacking, but may eventually come from using radioactive WBC tagging procedures. A synthesis of these two theories may in fact explain the etiology of venous ulceration.
Capillary Permeability↗
Autonomous replication in human cells of multimers of specific human and bacterial DNA sequences.
Using modules of a specific 2,712-bp human DNA sequence and a specific 2,557-bp Escherichia coli DNA sequence, we created plasmids containing between 1 and 12 modules of single or chimeric sequence composition and tested them in human cells for their autonomous replication ability. We found that replication efficiency per generation increased with successive addition of human modules, to essentially 100% by six copies. Although a single copy of the bacterial module had negligible replication ability, the replication efficiency per generation of 12 bacterial modules was 66%. Chimeras composed of human and bacterial modules displayed intermediate replication levels. We also used two-dimensional gel electrophoresis to physically map where replication initiated on a half human-half E. coli plasmid. Our results suggest that autonomous replication in human cells is stimulated by simple sequence features which occur frequently in human DNA but are more rare in bacterial DNA.
Ampicillin Resistance↗
The need for vascular access: a bell-shaped curve of progress.
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Catheterization, Central Venous↗
Clinical pharmacology.
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Formularies as Topic↗
Phenoxy herbicides and chlorophenols: a case control study on soft tissue sarcoma and malignant lymphoma.
A case control study on patients with soft tissue sarcoma and malignant lymphoma was undertaken to test whether there was any association between these diseases and past exposure to chlorinated phenoxy acid herbicides or chlorophenols. It was carried out over the period 1982-1988 in Victoria, Australia. Thirty males with soft tissue sarcoma and 52 males with malignant lymphoma were matched by age, place of residence and sex with one population control and one cancer control each. Exposure was assessed by personal interviews conducted by an occupational hygienist. Exposures within 5 years prior to diagnosis of each matched case were ignored, both for the cases and their matched controls. The estimated relative risks for definite or probable exposure to chlorinated phenoxy compounds or chlorophenols for at least 1 day were 1.0 (95% confidence interval (CI): 0.3-3.1) for soft tissue sarcoma and 1.5 (95% CI: 0.6-3.7) for malignant lymphoma. When the criterion for exposure was raised to more than 30 days, the estimated relative risks were 2.0 (95% CI: 0.5-8.0) for soft tissue sarcoma and 2.7 (95% CI: 0.7-9.6) for malignant lymphoma. Additional analyses were carried out for exposure of at least 1 day to phenoxy herbicides alone or chlorophenols alone. None of the estimated relative risks was significantly greater than unity.
Adult↗
Assessment of potential doses at the Maralinga and Emu test sites.
An assessment has been undertaken of potential doses to future aboriginal inhabitants of the Maralinga and Emu areas of South Australia, where nuclear weapons tests in the 1950s and 1960s have resulted in residual radioactive contamination. Radioactive material due to this program of tests and other experiments is still detectable several tens of kilometers from some of the test sites. Continued occupancy by individuals following an Aboriginal lifestyle could give rise to annual effective dose equivalents of several mSv within contours enclosing areas of several hundred square kilometers. The most significant dose pathways are calculated to be the inhalation of resuspended activity and ingestion of soil by infants. An analysis of the effects of uncertainties in the dose calculation has indicated the uncertainty distribution on predicted doses from the inhalation pathway.
Adult↗
Chlamydia trachomatis pneumonia induces in vivo production of interleukin-1 and -6.
Cytokine induction during Chlamydia trachomatis pneumonia may alter the pathogenesis or course of disease. We examined interleukin-1 (IL-1) and IL-6 production by measuring mRNA and bioactivity in murine lungs. mRNA and bioactivity for IL-1 alpha, IL-1 beta, and IL-6 increased after Chlamydia infection. These cytokines may be important in regulating host defenses against C. trachomatis.
Animals↗
Structured approach to the investigation of anaemia in patients with rheumatoid arthritis.
A group of 28 patients with rheumatoid arthritis who were severely anaemic were investigated for iron deficiency. On the basis of bone marrow studies, the patients were divided into two groups, those with and those without signs of stainable iron in the marrow. This grouping did not distinguish between the severity of their rheumatoid arthritis measured by clinical parameters. Measurement of the red cell count and biochemical parameters in the peripheral blood showed a statistical difference in red cell size, haemoglobin content, and iron binding capacity between the two groups. The statistical variation of these parameters, however, did not allow these measurements to predict bone marrow iron deficiency in any subject. Investigation of the upper gastrointestinal tract by endoscopy showed that acute macroscopic lesions were infrequently associated with anaemia. It was concluded that anaemia in association with rheumatoid arthritis may mimic iron deficiency anaemia, and that simple investigations of the peripheral blood do not accurately show the iron status of the reticuloendothelial system in the presence of a chronic inflammatory disease. For the investigation of severe anaemia in rheumatoid arthritis, bone marrow assessment of iron status should be performed as the initial investigation. In addition, iron deficient patients require investigation of the lower and the upper gastrointestinal tract.
Administration, Oral↗
Anaemia of chronic disease in rheumatoid arthritis: effect of the blunted response to erythropoietin and of interleukin 1 production by marrow macrophages.
Anaemia in rheumatoid arthritis (RA) is a common and debilitating complication. The most common causes of this anaemia are iron deficiency and anaemia of chronic disease. Investigations have suggested that interleukin 1 (IL-1) or tumour necrosis factor (TNF), or both, from monocytes associated with chronic inflammation are responsible for the anaemia of chronic disease. On bone marrow examination anaemia of chronic disease is characterised by the diversion of iron from the erythropoietic compartment into marrow macrophages. This phenomenon is termed failure of iron utilisation. In this study, CFU-E (colony forming unit erythroid; late red cell precursors) and BFU-E (burst forming unit erythroid; early red cell precursors) stem cells were cultured from 10 normal marrow samples and 12 marrow samples from patients with RA with iron deficiency anaemia and 10 samples from patients with RA with failure of iron utilisation. All patients with RA were anaemic (haemoglobin less than 100 g/l), Potential accessory or inhibitory cells of erythropoiesis (CD4, CD8, or CD14 positive cells) were removed before culture. Control marrow samples were studied in a similar manner. Normal marrow samples yielded 377 (17) CFU-E and 133 (6) BFU-E (mean (SD)) colonies for each 2 x 10(5) light density cells plated. CD4 ablation caused reductions of 62 and 100% in CFU-E and BFU-E colonies respectively. CD14 removal resulted in considerable but lesser reductions of 46% for CFU-E and 25% for BFU-E. In both groups of patients with RA, CFU-E colony numbers were significantly lower than those seen in normal control subjects, 293 (17) for patients with iron deficiency anaemia and 242 (35) for patients with failure of iron utilisation. BFU-E colony numbers were 102 (13) and 108 (20) respectively. In patients with RA, CD4 removal caused a significantly greater loss of CFU-E colonies compared with normal control subjects. Cytolysis of CD14 positive cells caused a reduction in CFU-E colonies in the two RA groups which was similar to that seen in normal subjects. In conclusion, patients with RA seem to have fewer CFU-E progenitors but essentially normal numbers of BFU-E stem cells. Our data suggest a stimulatory role for marrow CD4 and CD14 cells in erythropoiesis in patients with RA. Monocytes-macrophages (CD14 positive) are known to be producers of IL-1 or TNF, or both, however, the predicted increase in the CFU-E colonies on removal of CD14 cells is not seen. Therefore, if IL-1 or TNF, or both, are responsible for the impairment of erythropoiesis in patients with RA, marrow macrophages are unlikely to be the source. Moreover, these results indicate the probability of erythropoietin resistance on the basis of diminished CFU-E colony formation in patients with RA.
Anemia↗
Responses of peripheral blood cells to acute insulin-induced hypoglycaemia in humans: effect of alpha-adrenergic blockade.
Acute hypoglycaemia provokes rapid changes in peripheral blood cell counts. To examine possible adrenergic mechanisms modulating these changes, counts of peripheral blood cells including lymphocytes, granulocytes and red cells were measured in response to acute hypoglycaemia in a group of six normal subjects in control conditions (study 1), and during alpha-adrenergic blockade with phentolamine (study 2). In study 1 hypoglycaemia provoked a biphasic white cell response, with an early rise in lymphocyte count and a later rise in granulocyte count. The red cell count increased modestly following hypoglycaemia. During alpha-adrenergic blockade, the rise in total white cell count was diminished, with the rise in the lymphocyte count being greatly obtunded. The rise in the granulocyte count was unchanged. The increment of the red cell count during acute hypoglycaemia was abolished. These findings suggest that the increments of peripheral lymphocyte and red cell counts in response to acute insulin-induced hypoglycaemia are mediated via alpha-adrenoreceptors.
Acute Disease↗
The occurrence subtype and significance of haemopoietic inhibitory T cells (HIT cells) in myelodysplasia: an in vitro study.
This study examines the occurrence, subtype and possible significance of haemopoietic inhibitory T cells (HIT cells) in patients with myelodysplasia (n = 21), acute myeloblastic leukaemia (n = 8) and in normal subjects (n = 13) using an autostimulary CFU-GM stem cell assay. HIT cells were detected when colony numbers increased by 30% or more following T-lymphocyte subpopulation ablation. HIT cells occurred in 28% of the MDS patients, were always CD8-positive and never occurred in the normal subjects. Sequential studies in MDS patients with HIT cells and treated with low dose Ara-C showed no correlation between occurrence of these cells and clinical outcome. HIT cells appear to be a clinically irrelevant manifestation of the cell dysfunction associated with MDS.
Cytarabine↗
Propylene glycol dermatitis.
Propylene glycol is a commonly used vehicle for topical preparations. Although it is well suited for this purpose, it is capable of producing both primary irritant skin reactions and allergic sensitization. The literature on propylene glycol is reviewed, with particular attention to the nature of these adverse cutaneous effects. Guidelines for patients sensitive to propylene glycol are discussed.
Administration, Cutaneous↗