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Biomedical subjects

G W Jones

Publications and source records attributed to G W Jones.

At least 19 recordsLinked to original sources

The association of benign prostatic hyperplasia and cancer of the prostate.

There are a number of similarities between benign prostatic hyperplasia (BPH) and cancer. Both display a parallel increase in prevalence with patient age according to autopsy studies (86.2% and 43.6%, respectively, by the ninth decade), although cancer lags by 15-20 years. Both require androgens for growth and development, and both respond to antiandrogen treatment regimens. Most cancers arise in prostates with concomitant BPH (83.3%), and cancer is found incidentally in a significant number of transurethral prostatectomy (TURP) specimens (10%). The clinical incidence of cancer arising in patients with surgically treated BPH is approximately 3%. BPH may be related to a subset of prostate cancer which arises in the transition zone, perhaps in association with atypical adenomatous hyperplasia (AAH). It is important to exclude cancer in patients presenting with symptoms of bladder outlet obstruction presumably due to BPH. For such patients, we recommend digital rectal examination (DRE) and, at least in high-risk patients, serum prostate specific antigen (PSA) determination. Transrectal ultrasound (TRUS) should be employed in patients with elevated PSA levels to determine the volume of the prostate, the relative contribution of BPH to volume, and the PSA density (ratio of PSA level to volume). Biopsy should be obtained from any area suspicious for cancer. Early detection and treatment of cancer when it is localized offers the greatest chance for cure.

Adult

Prospective, conservative management of localized prostate cancer.

BACKGROUND: Currently, no randomized trials of the various treatment options for localized prostate cancer have been reported. Therefore, radical prostatectomy and external irradiation are offered as the primary management options and are thought by many to be curative. METHODS: All patients in this series with a confirmed diagnosis of cancer of the prostate, localized, were given the option of expectant management in addition to the popular ones. Therefore, 233 patients with localized Stage A and B cancer were observed prospectively and conservatively for a period of 22 years, with a management plan of watchful waiting for most patients until signs and/or symptoms of disease activity occurred. In 44 patients interstitial I-125 irradiation implantation and pelvic lymphadenectomy were performed in those who received surgical intervention. RESULTS: No patient received external irradiation or radical prostatectomy in this series. The overall survival of patients was not statistically different from the United States life-tables probability for men of similar ages when the study ended for reporting purposes in June 1989. Exclusive of the 6 patients lost to follow-up, 52 patients survived less than 3 years, whereas 181 patients have survived more than 3 years. CONCLUSIONS: Because of the favorable results in this expectant management study, it appears prudent that all patients with localized prostate cancer should have this management option as well as radical surgery or external irradiation.

Brachytherapy

Splenic radiation for corticosteroid-resistant immune thrombocytopenia.

OBJECTIVE: To determine the role of splenic radiation as a treatment for immune thrombocytopenia. DESIGN: Retrospective analysis of an open, nonrandomized investigation. SETTING: A regional cancer center, referred care, and primary care settings. PATIENTS: Eleven older patients with idiopathic thrombocytopenic purpura (ITP) and 8 patients with secondary immune thrombocytopenia refractory to corticosteroid treatment for whom surgery would have posed a high risk. INTERVENTION: A short course (1 to 6 weeks) of radiation therapy to the spleen (total dose, 75 to 1370 cGy) with or without concurrent and postradiation corticosteroid administration. MEASUREMENTS: Efficacy was assessed by measuring any increase in the platelet count and by monitoring the duration of response and side effects. RESULTS: Of 11 patients with ITP, 8 patients responded. Three patients had a sustained (greater than 52 weeks) increase in the platelet count to safe levels after therapy was discontinued. An additional patient had a sustained response but required intermittent, low-dose corticosteroids. Four other patients had increases in their platelet counts that lasted from 8 to 25 weeks. Two of the eight patients without ITP had a positive response, whereas four did not respond, and two were not evaluable. Patients had no adverse reactions to the radiation treatment. CONCLUSION: Splenic radiation can be a safe and effective method to raise the platelet count in older patients with ITP that is refractory to corticosteroids and in whom the risks associated with splenectomy are high.

Adrenal Cortex Hormones

Glucosyltransferase phase variation in Streptococcus gordonii modifies adhesion to saliva-coated hydroxyapatite surfaces in a sucrose-independent manner.

Phase variation of Streptococcus gordonii between high (Spp+) and low (Spp-) levels of glucosyltransferase (GTF) activity resulted in the greater adhesion of Spp- strains to saliva-coated hydroxyapatite (S-HA) in a washed-cell adhesion test. Specific GTF mutants did not show this response. Although washed Spp+ cells produced 5-fold or more glucan from sucrose than Spp- cells did under the conditions of the adhesion test, sucrose elevated the adhesion of both phenotypes to hydroxyapatite (HA) equally, but had no effect on adhesion to S-HA. This effect was not sucrose-specific, however, because equimolar amounts of other carbohydrates and NaCl elevated adhesion of both Spp types to levels similar to those seen with sucrose. Adhesion did not correlate with relative changes in cell hydrophobicity. These results suggest that, in addition to changes in GTF activity, other changes relevant to adhesion may occur during Spp phase variation.

Arabinose

Adhesion of glucosyltransferase phase variants to Streptococcus gordonii bacterium-glucan substrata may involve lipoteichoic acid.

Growing Streptococcus gordonii Spp+ phase variants, which have normal levels of glucosyltransferase (GTF) activity, use sucrose to promote their accumulation on surfaces by forming a cohesive bacterium-insoluble glucan polymer mass (BPM). Spp- phase variants, which have lower levels of GTF activity, do not form BPMs and do not remain in BPMs formed by Spp+ cells when grown in mixed cultures. To test the hypothesis that segregation of attached Spp+ and unattached Spp- cells was due to differences in adhesiveness, adhesion between washed, [3H]thymidine-labeled cells and preformed BPM substrata was measured. Unexpectedly, the results showed that cells of both phenotypes, as well as GTF-negative cells, attached equally well to preformed BPMs, indicating that attachment to BPMs was independent of cell surface GTF activity. Initial characterization of this binding interaction suggested that a protease-sensitive component on the washed cells may be binding to lipoteichoic acids sequestered in the BPM, since exogenous lipoteichoic acid inhibited adhesion. Surprisingly, the adhesion of both Spp+ and Spp- cells was markedly inhibited in the presence of sucrose, which also released lipoteichoic acid from the BPM. These in vitro findings suggest that, in vivo, sucrose and lipoteichoic acid may modify dental plaque development by enhancing or inhibiting the attachment of additional bacteria.

Bacterial Adhesion

Fluorescent markers for hypoxic cells: a study of nitroaromatic compounds, with fluorescent heterocyclic side chains, that undergo bioreductive binding.

Several novel compounds having both a 2-nitroimidazole nucleus and a fluorescent ring system in their molecular structure were prepared and evaluated as potential fluorescent probes for hypoxia. Bioreduction of nitroimidazoles, which is inhibited by oxygen, is known to lead to binding of bioreductive metabolites to cellular macromolecules and this provides a mechanism for binding the fluorescent moiety to hypoxic cells. These compounds can incorporate a wide range of fluorophors and can therefore be designed to suit the laser-line wavelengths available for excitation of fluorescence in the flow cytometer. Several nitroimidazoles with naphthalimide side chains were rapidly taken up into cells and became concentrated in the cells, thus reducing their concentration in the extracellular medium. This suggests a potential microscopic bioavailability problem with probes of this type when used in vivo as they would become progressively depleted in the extracellular fluid as they diffused from blood vessels, through layers of packed cells in tumors, to the hypoxic cells where they could undergo hypoxia-specific metabolism. Synthesis of nitroimidazoles with coumarin fluorophors led to several potentially useful probes for hypoxia; substituents on the coumarin fluorophor had a marked effect on the cellular fluorescence of these compounds.

Animals

Ecological implications of glucosyltransferase phase variation in Streptococcus gordonii.

When sucrose is provided as a substrate for glucosyltransferase (GTF), Spp+ cells of the oral bacteria Streptococcus gordonii grow embedded in an insoluble glucan mass associated with surfaces. Spp- phase variants with lower GTF activity, which either arise from or are grown with Spp+ cells, segregate preferentially as unattached cells in the culture supernatants. Conversely, Spp+ revertants preferentially accumulate on surfaces. GTF phase variation, therefore, may facilitate the dispersion of S. gordonii cells throughout the oral cavity.

Ecology

Sucrose-promoted accumulation of growing glucosyltransferase variants of Streptococcus gordonii on hydroxyapatite surfaces.

Streptococcus gordonii exhibits a phase variation involving expression of high (Spp+) or low (Spp-) glucosyltransferase activity. The related bacterial accumulation on hydroxyapatite (HA) and saliva-coated HA surfaces was examined and found to be significant. Spp+ cells growing anaerobically in a defined medium utilize about 30% of the glucose available from sucrose to make insoluble glucans. These glucans formed cohesive masses on HA beads, which contained 80 to 90% of the total bacteria. The bacterial polymer mass had a volume of about 40 microns3 and contained more than 5 x 10(10) viable cells per cm3. In the absence of sucrose, the beads were saturated by 1 x 10(8) to 2 x 10(8) Spp+ cells. Spp- bacteria, which make 30-fold less glucan than do Spp+ bacteria, did not accumulate on surfaces in numbers significantly above the saturation level of 1 x 10(8) to 2 x 10(8) cells in the presence or absence of sucrose. Insoluble glucan synthesized by Spp+ cells from sucrose also enabled these bacteria to accumulate on saliva-coated HA seven times more effectively than the Spp- cells and 10 times more effectively than the Spp+ cells grown in medium without sucrose.

Culture Media

Destruction of bovine coccidial oocysts in simulated cattle yards by dry tropical winter weather.

Post-weaning coccidiosis occurs in dry conditions in the dry tropics of north Queensland. Despite heavy faecal contamination, oocysts are difficult to detect in cattle yards. Experiments demonstrated the destruction of Eimeria bovis, E. ellipsoidalis and E. zuernii oocysts by natural factors in simulated yard conditions. Desiccation was rapid and temperatures as high as 48 degrees C developed within yard floor material although air temperatures did not exceed 27 degrees C. Oocyst numbers fell by 50% after 24 h, by 98% after 48 h, and were undetectable after 72 h. Oocysts were seen to collapse, and no development towards sporulation was noted.

Animals

A comparison of the effects of alfentanil/droperidol or fentanyl/droperidol on intra-ocular pressure.

The influence of two intravenous sedative regimens on intra-ocular pressure was investigated in conjunction with retrobulbar local anaesthesia. Forty patients were allocated randomly to either group A (alfentanil and droperidol) or group F (fentanyl and droperidol). Measurements of intra-ocular pressure, arterial pressure and oxygen saturation were made before operation, after premedication, after intravenous sedation and after surgery. Paco2 was also measured before and after operation. Each sedation technique caused a similar reduction in intra-ocular pressure. There was less effect on Paco2 and oxygenation in group A.

Aged

Spontaneous switching of the sucrose-promoted colony phenotype in Streptococcus sanguis.

Streptococcus sanguis on media containing 3% sucrose gives rise to characteristic hard cohesive colonies (designated Spp+). Populations of Spp+ bacteria (strain Challis) on sucrose media switch to a soft noncohesive phenotype (designated Spp-) at a frequency of 10(-4) to 10(-3). Spp- bacteria switch back to Spp+ bacteria at a similar frequency. Successive rounds of Spp variation were observed. The Spp phenotypic switch was associated with changes in extracellular glucosyltransferase activity.

Glucosyltransferases

Sequence analysis of rsk, a portion of the 95-kilobase plasmid of Salmonella typhimurium associated with resistance to the bactericidal activity of serum.

Increased sensitivity to killing by human serum complement occurs in Salmonella typhimurium strains in which the 95-kilobase virulence plasmid is integrated into the chromosome. This phenotypic change appears to be due to alterations in plasmid gene expression and is reversed by the presence of an autonomous plasmid bearing a cloned region of the virulence plasmid. Accordingly, this region has been termed rsk for reduced serum killing. Sequence analysis of the region reveals that rsk is composed of a series of direct 10-base-pair (bp) repeats with a 21-nucleotide periodicity. Two adjacent repeats are identical, but increasing loss of conservation is apparent with increased distance both 5' and 3' of these highly conserved 10-mers. The smallest isolated sequence which restores the serum-resistant phenotype is only 66 bp long and contains the two identical 10-mers and one degenerate 10-mer (8 of 10 bp conserved) 3' of these. The minimal rsk region of 66 bp does not appear to contain a coding sequence, or a promoter, for a structural gene. It is proposed that the minimal rsk is an isolated regulatory site involved in the regulation of the serum resistance of S. typhimurium. Integration of the 95-kilobase plasmid disrupts the normal regulation of virulence plasmid genes, resulting in an increase in the killing of the bacteria by complement activated by the classical pathway. The introduction of the minimal rsk on a multiple-copy plasmid restores resistance to serum killing, possibly through the titration of a trans-acting regulatory factor.

Bacterial Proteins

Evidence of coordinate regulation of virulence in Salmonella typhimurium involving the rsk element of the 95-kilobase plasmid.

Integration of the Salmonella typhimurium virulence plasmid into the chromosome reduces mouse virulence, serum resistance, and HeLa cell adhesion-invasion while prolonging lag time in minimal medium. The proposed virulence plasmid regulatory element, rsk, partially restores virulence and fully restores the other three phenotypes to wild-type levels. Plasmid curing reduces virulence without affecting the other phenotypes. rsk has no apparent effect on the cured strain.

Animals