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Biomedical subjects

R Barton

Publications and source records attributed to R Barton.

At least 19 recordsLinked to original sources

Selective intra-arterial infusion of high-dose cisplatin in patients with advanced head and neck cancer results in high tumor platinum concentrations and cisplatin-DNA adduct formation.

A group of 23 patients with advanced head and neck cancer were treated with highly selective intra-arterial (IA) cisplatin 150 mg/m2 delivered rapidly through microcatheters. The systemic effects of cisplatin were neutralized by concurrent administration of sodium thiosulfate. Two-to-threefold higher tumor platinum contents were detected in tumor biopsies after selective IA cisplatin administration compared to historical controls (treated with 100 mg/m2 IA). Cisplatin-induced DNA modification in human tumor biopsies was quantitated using the antiserum NKI-A59. High levels of cisplatin DNA adducts were detected which correlated linearly with the tumor platinum content (r2 = 0.62). The addition of radiotherapy to this high dose intensity cisplatin treatment resulted in a 92% complete response (CR) rate (12 of 13 patients achieved a CR). Since no difference in tumor platinum content was detected between patients receiving or not receiving radiotherapy (13 and 10 patients, respectively), but the response rate was substantially different (12 CR and 1 partial response with radiotherapy versus 6 partial and 4 non-responders without radiotherapy), these data suggest that the high platinum levels achieved by selective IA infusion were sufficient to produce enough interaction with radiotherapy to cause a 92% CR rate. Whether this interaction is additive or synergistic is as yet unclear.

Antineoplastic Agents

Suppression of cytoplasmic senescence in Neurospora.

We have shown that senescence in Kalilo strains of Neurospora, caused by a linear mitochondrial plasmid called kalDNA, is suppressible by existing variants of the nuclear genome. The suppressors are manifested by 4:4 segregation of senescence and immortality in asci from crosses between senescent female strains and males chosen from non-senescent candidate stocks. In one case of suppression, the asci also show segregation at the plasmid level. There is a reduction of kalDNA to barely detectable levels in the four ascospores showing immortality, so this suppressor evidently influences the maintenance of the plasmid itself. In the other case of suppression, the phenotypic segregation is not correlated with segregation at the plasmid level, and all eight ascospores in the asci show both free and inserted forms of kalDNA. This suggests that the suppression genotype provides a way of tolerating the presence of the plasmid rather than diminishing it. However, the allele f, which provides an analogous kind of suppression for the cytoplasmic mutation poky, does not suppress Kalilo or Maranhar senescence. Suppression is hence shown to be a possible option for host strains to combat the plasmid in nature, but no examples of suppressors were found in a limited survey of natural isolates. In addition, we have shown that long-lived, presumably non-senescent, strains do not arise by suppressor mutation, but lose senescence plasmid DNA by another mechanism.

Cytoplasm

Recurrent medulloblastoma: frequency of tumor enhancement on Gd-DTPA MR imaging.

Thirty-two children with medulloblastoma were evaluated postoperatively with conventional and gadolinium-enhanced MR imaging. Eleven patients had abnormal cranial MR studies; nine of these had recurrent tumor. In six patients recurrent tumor enhanced with Gd, while in the other three patients recurrent tumor did not enhance. The remaining two patients had areas of abnormal Gd enhancement that were caused by radiation-induced breakdown of the blood-brain barrier rather than by recurrent tumor. This study shows that not all recurrent medulloblastoma enhances and that the absence of Gd enhancement does not necessarily indicate the absence of recurrent tumor.

Adolescent

Recurrent medulloblastoma: frequency of tumor enhancement on Gd-DTPA MR imaging.

Thirty-two children with medulloblastoma were evaluated postoperatively with conventional and gadolinium-enhanced MR imaging. Eleven patients had abnormal cranial MR studies; nine of these had recurrent tumor. In six patients recurrent tumor enhanced with Gd, while in the other three patients recurrent tumor did not enhance. The remaining two patients had areas of abnormal Gd enhancement that were caused by radiation-induced breakdown of the blood-brain barrier rather than by recurrent tumor. This study shows that not all recurrent medulloblastoma enhances and that the absence of Gd enhancement does not necessarily indicate the absence of recurrent tumor.

Adolescent

A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses.

Rhinoviruses, which cause common colds, possess over 100 serotypes, 90% of which (the major group) share a single receptor. Lymphocyte function associated molecule 1 (LFA-1) mediates leukocyte adhesion to a wide variety of cell types by binding to intercellular adhesion molecule 1 (ICAM-1). We demonstrate identity between the receptor for the major group of rhinoviruses and ICAM-1. A major group rhinovirus binds specifically to purified ICAM-1 and to ICAM-1 expressed on transfected COS cells, and binding is blocked by three ICAM-1 monoclonal antibodies (MAb) that block ICAM-1-LFA-1 interaction, but not by an ICAM-1 MAb that does not block ICAM-1-LFA-1 interaction. This suggests that the ICAM-1 contact site(s) for LFA-1 and rhinoviruses is proximal or identical. In addition, ICAM-1 MAb block the cytopathic effect in HeLa cells mediated by representative major but not minor group rhinoviruses. ICAM-1 is induced by soluble mediators of inflammation, suggesting that the host immune response to rhinovirus may facilitate spread to uninfected cells.

Antibodies, Monoclonal

Pharmacological comparison of active and passive experimental allergic encephalomyelitis in the rat.

Models of actively induced and passively transferred experimental allergic encephalomyelitis (EAE) have been compared in the rat. The time of disease onset, severity of clinical symptoms and percent incidence were compared and assessed for their suitability for evaluation of immunosuppressive agents. The passive EAE model had an earlier disease onset (6 +/- 0.1 days) and 100% of the cell recipients (n = 45) developed severe clinical symptoms, including paralysis of the tail and hind limbs. In contrast, the active EAE model had a mean disease onset day of 13 +/- 0.1 and only 53% of the induced rats (n = 85) developed EAE clinical symptoms which were variable. The average symptom score in both models was inhibited by dexamethasone (1 mg/kg/day p.o.; day 0 to 3), methotrexate (3 mg/kg i.p. single dose; day 1) and cyclosporin A (30 mg/kg/day p.o.; day 0 to 7). The above study indicates that the passive EAE model is more advantageous for pharmacologic evaluation of immunosuppressive agents.

Animals

Alcohol promotion on television.

A study in the United Kingdom has shown that the advertising of alcohol on television targets young people particularly. There is a strong case for banning alcohol advertisements from this medium.

Adolescent

Un-health promotion: results of a survey of alcohol promotion on television.

To estimate how widely and to whom alcoholic drinks are promoted 1258 television advertisements were studied over a 10 week period that included the Christmas and New Year holidays in 1986-7. A total of 156 advertisements (12%) promoted alcohol, and this percentage increased significantly over the holiday period to 17%. These advertisements were longer than those advertising other products, and just over half (56%) occupied the first position in commercial breaks. During sports programmes and between the hours of 1800 and 1900 there was an increase in the number of advertisements for alcohol, but there was no difference before and after 2100. It was found that the extent and influence of the promotion of alcohol were great and that such advertising is seen by many children and adolescents.

Advertising

Variation in cytoplasmic microtubule organization and spindle length between the two forms of the dimorphic fungus Candida albicans.

Candida albicans is a dimorphic fungus capable of growing as a budding yeast and as a filamentous hypha. We have used the technique of immunofluorescence to study the changes in the microtubule cytoskeleton during the cell cycle in both growth forms. This approach has revealed the presence of an extensive system of microtubules, including cytoplasmic microtubules and a rod-like intranuclear spindle. We have provided a complete description of the arrangement of cytoplasmic and spindle microtubules at each phase of the yeast cell cycle. A novel and characteristic feature of the yeast phase of Candida is the presence of an array of short microtubules at the neck of the doublet cell. This neck-associated array (NAA), is apparently organized independently of the main microtubule-organizing centre, the spindle pole bodies, at late anaphase. Analysis of microtubule patterns in the hyphal state reveals that the general arrangements of microtubules are similar to those seen in the yeast phase. These patterns suggest a role for the cytoplasmic microtubules in the nuclear migration that occurs during hyphal growth. A major finding is that the mitotic spindle in hyphae is considerably longer (12-20 microns) than the spindle in yeast cells (7-8 microns). This may reflect the role of the hyphal mitotic spindle not only in nuclear division but also in the positioning of the daughter nuclei at the centres of hyphal compartments.

Candida albicans

How financial barriers can frustrate good arthritis care.

Current insurance practices discriminate against the arthritis patient who does not require acute-level care. Such practices inadequately deal with the financial barriers to the procurement of the health care services that are effective in relieving pain and increasing mobility and quality of life. The result often is frustration for both the patient and the physician.

Aged

Reversal of gamma-radiation-induced leukemogenesis in mice by immunomodulation with thiabendazole and dinitrofluorobenzene.

The effect of thiabendazole (TBZ) and dinitrofluorobenzene (DNFB) on radiation-induced leukemogenesis was investigated in the C57BL/6 mouse model. Administration of TBZ-DNFB during, post, or during and post irradiation successfully blocked leukemogenesis, as indicated by the absence of leukemia blast cells in thymus and peripheral blood, as well as prevented thymic lymphoma. TBZ-DNFB treatment prevented the development of leukemia when studies were terminated both after 7 months of last irradiation (disease fully developed) and after 5 months of last irradiation (disease in the process of development). This TBZ-DNFB treatment also resulted in a significant increase in survival.

Animals