Biomedical subjects
Publications and source records attributed to G W Jones.
Light and ultrastructural findings in a mixed mesodermal tumor of the urinary bladder are reported. The mesenchymal component of the tumor contained undifferentiated mesenchymal cells and cells with chondroblastic differentiation. The neoplastic chondrocytes displayed an abundance of cytoplasmic microfilaments and had a scalloped cell surface.
The interactions which brought about the invasion of HeLa cells by Salmonella typhimurium consisted of a sequence of three phases. Initially, the motility of the bacteria facilitated their contact with the HeLa cells whereupon the bacteria became attached in a reversible manner (i.e. the bacteria could be removed readily by washing the HeLa cell monolayers with Hanks' Balanced Salt solution). The binding forces responsible for reversible attachment were probably the weak long-range forces of the secondary minimum level of attractive interactions between the bacterium and the HeLa cell. Reversible attachment was a necessary interlude before the bacteria became irreversibly attached to the surfaces of the HeLa cells (i.e. the bacteria were no longer removed by the washing procedure that removed the reversibly attached salmonellae). Irreversible attachment was prevented in solutions of low ionic strength; the forces responsible were probably those of the primary minimum generated between the HeLa cell and a bacterial adhesion which was capable of acting over only short distances between the reversibly attached bacterium and the HeLa cell (i.e. probably less than 15 nm). Only irreversibly attached bacteria proceeded to the third phase and were internalized by the HeLa cells.
The association of the haemagglutinating activities of Salmonella typhimurium cultures with bacterial adhesion to HeLa cells, and the internalization of the bacteria by HeLa cells, was studied. Adhesion was not inhibited by alpha-methyl-D-mannoside (i.e. adhesion was mannose-resistant), and only four of the six strains tested produced type 1 fimbriae and the associated mannose-sensitive haemagglutinin (MSHA). The other two strains belonged to the non-fimbriate FIRN biogroup. Cultures of all six strains contained a mannose-resistant haemagglutinating (MRHA) activity when grown at 37 degrees C, but cultures of only one fimbriate and one non-fimbriate strain did so when grown at 18 degrees C. From the comparison of cultures grown at 18 degrees C and 37 degrees C, and of mutant strains with the phenotypes MRHA-negative/MSHA-positive, or MRHA-positive/MSHA-negative, it was concluded that the MRHA activity was responsible for the attachment of salmonellae to HeLa cells. Only bacterial adhesion that was resistant to mannose resulted in the internalization of the bacteria by the HeLa cells.
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Microcarcinoma (incidental, latent) of the prostate gland occurred with a frequency of 11.7% and at an age-adjusted incidence rate (world standard) of 40.6% per 1000 necropsies in the sampled black male population. The frequency of microcarcinoma of the prostate in black males in Washington, D.C., is essentially the same as the frequency of latent carcinoma in other ethnic groups and in other geographic areas. Of the patients studied clinically, fifty-one percent (51%) were in low stage (Stages I and II) disease; sixty-three percent (62.7%) had a well differentiated, Grade I, carcinoma of the prostate; and forty-two percent (42.4%) were in the 65-74 age group. Mean plasma testosterone and estrone levels were significantly higher in cancer patients than in age-matched hospitalized controls. The factor with the highest risk ratio was urinary tract symptoms occurring 10 years or longer before the onset of the present complaints which led to the diagnosis or prostatic carcinoma. Although our studies did not directly implicate diet as a risk factor, published reports strongly suggest diet as a critical factor in the development of prostatic carcinoma.
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A comparison of carcinoma of the prostate gland in a low-incidence Nigerian (Ibadan) population and a high-incidence U.S. Afro-American (Washington, D.C.) population was the purpose for this study, initiated in 1973. The frequency of carcinoma (micro- and invasive) was determined in consecutive necropsy cases from hospitals in Ibadan, Nigeria, Accra, Ghana and Washington, D.C. The results of these clinical, epidemiologic and morphologic studies are reported. Clinically, the peak incidence of carcinoma of the prostate in Nigerian males in Ibadan and in American males in Washington, D.C. was in the 65-74 age group. The median age of patients was 66.4 years in Ibadan and 69.2 years in Washington, D.C. Seventy-five percent of Nigerian and 49% of American patients were in stages III and IV. Overall, the distribution by grade of neoplasms in surgical material from Ibadan and Washington, D.C. was similar. Plasma testosterone and estrone levels were significantly higher (p < 0.05 and p < 0.001) in U.S. patients than in U.S. controls and higher (p < 0.001 and p < 0.05) in U.S. patients than in Nigerian patients with prostatic carcinoma. Plasma testosterone levels were significantly lower (p < 0.05) in Nigerian patients than in Nigerian controls. Estrone levels were not significantly different in Nigerian patients than controls. Nigerian patients were more sexually active throughout their lives than American patients; however, they reported a higher incidence of impotence than U.S. patients in the immediate 5 years preceding the diagnosis of prostatic carcinoma. Nigerian respondents (patients and controls) arrived at puberty later than their American counterparts. Within each of the two population groups, the factor with the highest relative risk ratio was lower urinary tract symtoms occurring 10 years or longer before the onset of the present complaints which led to the diagnosis of prostatic carcinoma. Nigerian and U.S. patients were more sexually active than controls. Microcarcinoma (incidental, latent) of the prostate gland occurred with a frequency of 11.8% and at an age-adjusted incidence rate (world standard) of 40.6 per 1000 necropsies in the sampled U.S. black male population. The age-adjusted incidence rate (world standard) for microcarcinoma in the combined West African (Accra and Ibadan) series (36.7/1000) was almost equal to the rate (40.6/1000) in the Washington, D.C. series.
This paper describes an open assessment of cinoxacin in the treatment of 30 outpatients with symptomatic urinary tract infections caused by Escherichia coli, Klebsiella, Proteus mirabilis, and Enterobacter. Twenty-seven patients (90 percent) had a satisfactory clinical response and in 26 patients, there was a satisfactory microbiological response with elimination of the pathogen. Mild side effects were reported by three patients, none of whom stopped therapy. It is concluded that cinoxacin will be useful in the treatment of urinary tract disease because of the high urinary antibacterial activity produced. The relatively low incidence of side effects and convenience of twice-daily dosage should encourage good compliance by patients treated outside the hospital setting.
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.
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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.
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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.
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.
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.
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.
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.