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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

The fine structural localization of acid phosphatase in pore cells of embryonic and newly hatched Deroceras reticulatum (Pulmonata: Stylommatophora).

The fine structure of the pore cells in pre- and post-hatched Deroceras reticulatum is described. The cells have been divided into three main types on morphological grounds, one type being particulary rich in glycogen. Certain pore cells contain haemocyanin granules in grooves below cytoplasmic tongues, and in characteristic double-membrane-bounded vesicles within dilated cisternae of rough endoplasmic reticulum, as well as in other identified areas. All types of pore cells show fine fibres reminiscent of collagen associated with the basal lamina and pore complexes. In addition to acid phosphatase activity in lysosomes and Golgi elements, intra- and extracisternal activity has been demonstrated in association with the rough endoplasmic reticulum. The intracisternal activity is in close proximity to the Golgi apparatus and may represent enzyme that is about to enter the GERL system. Extracisternal activity may be associated with cellular lysis and death, or may represent local areas of degradation leading to cytodifferentiation. Remnants of lysed pore cells appear to be taken up by connective tissue amoebocytes.

Acid Phosphatase

Gonadal stromal tumor in black male.

A twenty-five-year-old black male presented with a right testicular mass which had progressively increased in size over three years. He was in good health and noted no other general abnormalities. Taking all malignant precautions, excisional biopsy of the lesion revealed gonadal stromal tumor by frozen section. The testis was left in situ, and the patient has continued to remain asymptomatic.

Adult

Antibacterial activity in colostrum and milk associated with protection of piglets against enteric disease caused by K88-positive Escherichia coli.

Piglets suckled by dams that had been vaccinated with K88 antigen were significantly more resistant to deaths caused by neonatal diarrhea after challenge with a large dose of a K88-positive enteropathogenic strain of Escherichia coli than piglets suckled by control dams. The factors most likely to be involved in protection of the piglets were investigated by comparing the antibacterial activities of serum and mammary secretions from the two groups of dams. Vaccination stimulated the production of K88 antibodies, which were associated with anti-adhesive activity directed against the adhesive properties of the K88 antigen, and of O8 antibodies; the latter antibodies were attributed to traces of O8 antigen in the vaccine. Neutralizing activity against heat-labile enterotoxin was present in several dams before vaccination but was not stimulated by bacteriostatic activities were similar in serum and mammary secretions from both groups of dams and appeared to play no significant role in the protective after parturition were atrributed to exposure of the dams to the challenge strain excreted by the piglets. It was concluded that neutralization of the adhesive properties of K88 antigen by K88 antibodies in colostrum and in milk contributed significantly to the protection of piglets from vaccinated dams. However, the contribution of antibacterial activities associated with the greater levels of O8 antibodies in colstrum from the vaccinated group cannot be entirely excluded.

Agglutinins

Adhesive properties of Vibrio cholerae: adhesion to isolated rabbit brush border membranes and hemagglutinating activity.

Adhesion of vibrios to the small intestine may occur (i) by association of the bacteria with secreted mucus gel or (ii) by adherence of the bacteria to the surface of epithelial cells. In the present study, vibrios readily adhered to isolated brush border membranes obtained from rabbit intestinal epithelial cells. Adhesion was temperature dependent and required the presence of divalent cations such as calcium. The agglutination of human O erythrocytes by Vibrio cholerae was observed also, and the hemagglutination test appeared to detect the same mechanism that was involved in the adhesion of vibrios to brush borders. When the bacteria were grown in broth they were adhesive and hemagglutinating, but vibrios grown on agar plates or suspended in buffer for 15 min at 37 C lacked these abilities, even though they retained undiminished motility. These two model systems differed, however, in that strontium promoted only adhesion to brush borders. The significance of this difference remains to be determined. Vibrios were observed to penetrate intestinal mucus gel and occasionally to become entrapped in it. However, there was no evidence that vibrios attached to mucus gel.

ABO Blood-Group System

Adhesive properties of Vibrio cholerae: nature of the interaction with isolated rabbit brush border membranes and human erythrocytes.

Nonmotile vibrio mutants lacked the ability to adhere to rabbit intestinal brush border membranes and to agglutinate human group O erythrocytes, but motile revertant vibrios isolated from such strains expressed adhesiveness equivalent to that of the original parent. Two possible explanations for the relation between vibrio motility and adhesion in these assays systems are (i) that the rate of adhesion depends on the rate of chance contact brought about by motility, and (ii) that the flagellum either acts as a carrier for the bacterial adhesin or may itself be the adhesin. The present study indicates, however, that the lack of adhesion by nonmotile vibrios did not depend on motility as such and did not involve greater rates of elution. Increasing the rate of contact between nonmotile vibrio mutants and brush border membranes by compaction did not restore the adhesive properties of the defective strains. Accordingly, we speculate that the flagellum may function in some indirect way that allows the expression of the adhesive properties, such as by acting as a carrier for a specific vibrio adhesin. Adhesion to brush borders and agglutination of human group O erythrocytes was specifically inhibited by L-fucose and various glycosides of L-fucose and to a lesser extent by D-mannose. Vibrios adhered specifically to agarose beads that carried covalently linked L-fucose on their surfaces. The results suggest that L-fucose-containing structures of eukaryotic cell surfaces may function as receptors for the vibrio adhesin and may therefore be an important determinant of host susceptibility.

Animals

Adhesive properties of Vibrio cholerae: nature of the interaction with intact mucosal surfaces.

Two companion papers in this series have characterized the interaction between Vibrio cholerae and the surfaces of eukaryotic cells. The present paper reports studies of the association between vibrios or Salmonella enteritidis and intact slices of intestinal tissue. A significant number of differences were noted in the characteristics of bacterial adhesion in these systems. The results are interpreted to indicate the presence of at least two receptors for vibrio adhesion on the mucosal surface of the rabbit small intestine. The receptor mediating the adhesion of salmonella appeared to be distinct from these. A primary role for bacterial motility in the process of adhesion of vibrios to mucosal surfaces could not be demonstrated in the assay systems studied. Rather, loss of motility in mutant vibrios appeared to be correlated with the simultaneous loss of adhesive factors (adhesins) from the bacterial surface. The inhibition of vibrio adhesion to slices of intestinal tissues by antibody to the heat-stable antigens of V. cholerae occurred in the absence of bacterial agglutination. Agglutination in this assay system appeared to be an artifact in that it could be observed only in experiments where extremely high concentrations of vibrios were used. We speculate that such high vibrio concentrations are not likely to be present in humans at the time of infection and that agglutination in the lumen of the intestine might therefore play only a minor role in prophylactic immunity against natural cholera and other enteric infections of humans.

Agglutination

Epidemiologic association between Gonorrhea and prostatic carcinoma.

The curves for death rates from prostatic cancer and gonorrhea incidence rates in Denmark, over a span of thirty years, matched well with a lag period of forty-five years. Moreover, a retrospective study conducted in the United States involving 75 cancer patients and 75 age-matched controls demonstrated a statistically significant association between gonorrheal infection and subsequent development of prostatic carcinoma. Two postulates are presented: the viral-venereal and the chronic infection theories. The recent increase in incidence of prostatic cancer in the United States could be the beginning of an epidemic in which astronomically high rates may be reached.

Adolescent

An attempt to identify the intestinal receptor for the K88 adhesin by means of a haemagglutination inhibition test using glycoproteins and fractions from sow colostrum.

The K88 antigen of Escherichia coli specifically adheres to the piglet intestinal cell; a solution of this antigen agglutinates guinea-pig red cells at 4 degrees C. The latter reaction was used as a model of the former, using inhibition of haemagglutination as an index of specific combination with the K88 adhesin. Inhibition was found with mucous glycoproteins and chemical modification of their heterosaccharide residues by mild acid hydrolysis, periodate oxidation or the Smith degradation procedure suggested that the terminal beta-D-galactosyl structure in a heterosaccharide sidechain of a glycoprotein might combine specifically with the K88 adhesin and inhibit haemagglutination. One serum glycoprotein (fetuin), after exposure of its subterminal beta-D-galactosyl residue, also inhibited haemagglutination, but high inhibitory activity was exhibited by some submaxillary glycoproteins in which this structure was absent or not prominent. It was concluded that in some cases inhibition of haemagglutination by glycoprotein was non-specific. No inhibition was found using glycosaminoglycans, glycogen or any simple sugar or glycoside. Sow colostrum was inhibitory but this was associated mainly with its gamma-globulin fraction. Some inhibitory activity was traced to a colostral glycopeptide fraction of low molecular weight but the smaller colostral oligosaccharides were not inhibitory; the composition of these components in sow colostrum is reported.

Alpha-Globulins