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Biomedical subjects

P Gilbert

Publications and source records attributed to P Gilbert.

At least 145 records · Page 8Linked to original sources

Surgical treatment of Peyronie's disease.

Surgical measures usually represent the last step in the treatment of Peyronie's disease. Straightening of the penile shaft and relief of pains during erection are the main goals of the operation. From December 1987 to April 1990, 11 patients with a mean age of 58.3 years underwent surgical treatment. Three of them complained of erectile dysfunction prior to surgery. The plaques were located distally in 8 patients, proximally in 1 patient and in the middle of the shaft in 2 patients. Complete resection was performed and defects of the tunica albuginea were closed by means of running sutures (3 patients) or grafts of autologous skin (5 patients) and lyophilized dura mater (3 patients), respectively. After a mean follow-up of 21 months, 6 patients reported spontaneous erections, whereas 3 patients needed corpus cavernosum autoinjection therapy. In 2 cases implantation of a penile prosthesis was necessary. Surgical treatment of Peyronie's disease yields satisfactory results if conservative therapy proves unsuccessful. However, diagnostic evaluation of erectile dysfunction should precede operative treatment and if present, be treated accordingly.

Humans↗

Podocytes in glomerulus of rat kidney express a characteristic 44 KD protein.

We describe a new monoclonal antibody (MAb) directed against glomerular visceral epithelial cells (podocytes), generated by immunization with isolated rat kidney glomeruli. In immunoblotting experiments this MAb (IgG1 subclass) reacted with a 44 KD protein. In cryostat sections of normal rat kidney the MAb stained glomerular podocytes; therefore, we called the antigen pp44 (podocyte protein 44 KD). On 0.5-micron cryostat sections the signal could be more precisely ascribed to the podocyte foot processes, whereas the cell bodies appeared virtually unreactive. On ultra-thin frozen sections pp44 was found within the cytoplasm of podocyte foot processes at their origin from their parent processes. The podocyte cell membrane was not labeled. All other parts of the nephron were unreactive. An additional but weaker immunoreaction was found in the arterial endothelium; the endothelia of other vessels (peritubular capillaries, veins) were negative. In human kidney anti-pp44 revealed the same staining pattern as in rat kidney. The expression of pp44 was also studied in newborn rat kidney. The early stages of glomerular development (renal vesicle, S-shaped body) were negative. pp44 first appeared during the capillary loop stage, i.e., when formation of podocyte foot processes commences. In comparing the present results with published data, pp44 is clearly different from other antigens thus far described in podocytes. From the results of this investigation we conclude that pp44 represents a novel cytoplasmic protein of podocytes. Our data suggest a cytoskeletal role for pp44 in preserving the complex architecture of podocytes. This idea is confirmed by the simultaneous appearance of foot processes and anti-pp44 immunoreactivity during glomerular development.

Animals↗

Surface characteristics and adhesion of Escherichia coli and Staphylococcus epidermidis.

Surface hydrophobicity, surface electrokinetic potential and the ability to adhere to nitric-acid cleansed glass surfaces has been assessed throughout the growth, in batch culture, of Escherichia coli and Staphylococcus epidermidis. In both instances adhesiveness and surface hydrophobicity decreased in early- to mid-exponential phase. Cell surface charge, on the other hand became more electro-negative for E. coli but electro-neutral for Staph. epidermidis as the cells proceeded to divide. Adhesiveness correlated directly with surface electronegativity and hydrophobicity for Staph. epidermidis but inversely with surface electro-negativity for E. coli.

Bacterial Adhesion↗

Surface hydrophobicity and dispersal of Pseudomonas aeruginosa from biofilms.

A novel method of cell culture was employed to control the growth-rate of bacterial biofilms [1]. Cell-surface hydrophobicity increased progressively with growth rate for planktonic, chemostatgrown Pseudomonas aeruginosa and also for cells, resuspended from the biofilms. Dependence of surface hydrophobicity upon growth rate was greater for the planktonic cells. Newly-formed daughter cells, shed from the biofilms, were in all cases more hydrophilic than their adherent counterparts and demonstrated only slight growth rate dependency for this property.

Pseudomonas aeruginosa↗

Case report 620. Progressive systemic sclerosis (PSS) with paraspinous and intraspinous calcifications.

Progressive systemic sclerosis (PSS) is a connective tissue disorder of unknown etiology and pathogenesis characterized by fibrosis of the skin (scleroderma) and variable involvement of several organ systems including the gastrointestinal tract, lungs, heart, and kidneys. Calcinosis cutis is a frequent finding, commonly seen in the soft tissues of the fingertips and over the knees and elbows. Calcifications may also occur in areas of muscle necrosis and have been reported in articular synovium. This report describes a patient with PSS in the form of subcutaneous calcifications and scleroderma who was noted to have extensive paraspinous and intraspinal calcific deposits, causing severe narrowing of the spinal canal. The radiographs of 66 patients with PSS seen at Northwestern Memorial Hospital of soft tissue calcifications.

Calcinosis↗

Susceptibility of bacterial biofilms to tobramycin: role of specific growth rate and phase in the division cycle.

A novel method of cell culture, enabling growth rate control of sessile Gram-negative populations, has been employed to assess the sensitivity of Escherichia coli towards the aminoglycoside antibiotic, tobramycin. Changes in sensitivity, dependent on the growth rate, were compared with those for suspended populations grown in a chemostat and also those for newly-formed daughter cells shed from the biofilm during its growth and development. At specific growth rates up to 0.3 h-1 the susceptibility both of the resuspended biofilm cells and of their planktonic, chemostat grown controls increased in proportion to the growth rate. As the growth rate was increased further (up to 0.7h-1), the susceptibility of the resuspended biofilm cells remained high, whilst that of the planktonic controls decreased. Newly-formed daughter cells, dislodged from the biofilm, demonstrated a uniformly high sensitivity to the antibiotic at all growth rates. This sensitivity corresponded to that of the fastest-growing cells resuspended from biofilms. Lack of growth rate dependency of killing for the newly-formed daughter cells and their high sensitivity to tobramycin suggested that tobramycin activity might vary during the cellular division cycle. Indeed, when synchronous populations were exposed to tobramycin at various times during their division cycle, sensitivity decreased markedly 20 min before the onset of septation, and increased as septation began. Regulation of the cellular division cycle might therefore account, at least partly, for the observed effects of growth rate on susceptibility.

Animals↗

Effect of growth-rate on resistance of gram-negative biofilms to cetrimide.

A method of cell culture, which allows control of growth rate for sessile Gram-negative populations, has been employed to assess the sensitivity of Escherichia coli biofilms to the antiseptic compound, cetrimide. Growth-rate-dependent changes in sensitivity were compared for chemostat-grown, planktonic cells, for cells resuspended from the biofilm and also for newly formed daughter cells shed from the biofilm during its growth and development. Susceptibility to cetrimide decreased in all instances with increases in growth-rate up to mu = 0.15 h-1. As growth rate was increased beyond this value then sensitivity increased in proportion to the rate of division. At rates of growth less than mu = 0.15 h-1 the susceptibility of the biofilm-derived cells and their offspring was significantly less than that of cells of planktonic origin.

Anti-Infective Agents, Local↗

Growth inhibitory and biocidal activity of some isothiazolone biocides.

Similar patterns of growth inhibition were observed for the three biocides, benzisothiazol-3-one (BIT), 5-chloro-N-methylisothiazol-3-one (CMIT) and N-methylisothiazol-3-one (MIT) against Escherichia coli ATCC 8739 and Schizosaccharomyces pombe NCYC 1354. After periods of induced stasis, proportional to biocide concentration, growth proceeded at an inhibited rate. Extrapolation of the static periods and inhibited growth rates against biocide concentration gave minimum growth inhibitory concentration estimates of 0.1-0.5 micrograms/ml for CMIT, 15-20 micrograms/ml for BIT and 40-250 micrograms/ml for MIT. Patterns of growth inhibition by CMIT and induced morphological changes in inhibited cultures suggested this compound to also inhibit initiation of DNA replication. Growth inhibitory activity was rapidly quenched by the addition of thiol-containing materials such as glutathione and cysteine. The activity of CMIT was additionally quenched by the presence of the non-thiol amino acids valine and/or histidine. These results suggest that the chlorinated isothiazolones can react with amines as well as with essential thiol groups.

DNA Replication↗

Chemical reactivity of some isothiazolone biocides.

Chemical reactions between the isothiazolone biocides, N-methylisothiazol-3-one (MIT), benzisothiazol-3-one (BIT) and 5-chloro-N-methylisothiazol-3-one (CMIT) with cysteine have been investigated by u.v. and NMR spectroscopy. At physiological pH all three agents interacted oxidatively with thiols to form disulphides. Further interaction with thiols caused the release of cystine and formation of a reduced, ring-opened form of the biocide (mercaptoacrylamide). In an analogous fashion to the initial reaction the mercaptoacrylamide reacted with another molecule of biocide to give biocide dimers. NMR spectral studies indicated that for CMIT the mercaptoacrylamide form is capable of tautomerization to a highly reactive thio-acyl chloride. Formation of mercaptoacrylamide was in all cases highly pH-dependent. Alcohol dehydrogenase was insensitive to all three agents but was highly sensitive to CMIT when co-administered with dithiothreitol. Capacity to form a thioacyl chloride from the mercaptoacrylamide is suggested to account for much of this enhanced activity. Stopped-flow spectroscopic studies showed rates of reaction with glutathione (GSH) to directly parallel antimicrobial activity. Additionally, CMIT was able to react directly with both ionization states of GSH (pH 7-10) whilst BIT and MIT appeared only to interact when the glutamyl-nitrogen of GSH was charged (pH 8.5).

Alcohol Dehydrogenase↗

Barrier properties of the gram-negative cell envelope towards high molecular weight polyhexamethylene biguanides.

The antimicrobial activities of four discrete molecular weight fractions of polyhexamethylene biguanides towards a number of Escherichia coli strains have been investigated. Whilst activity of the polymers was observed to increase in proportion to polymerization number, the dependence of activity upon molecular weight was five times greater towards sphaeroplasts than towards whole cells. This suggested that the cell envelope, whilst not conferring complete resistance to the agents, did provide a significant exclusion barrier. Comparison of the activities towards rough and deep-rough lipopolysaccharide strains showed growth inhibitory activity, but not bactericidal activity nor respiratory inhibition, to be enhanced in the rough strains. Uptake studies showed mixed H- and C-type adsorption with significantly greater numbers of high-affinity binding sites being associated with rough than deep-rough lipopolysaccharide. The binding affinity of polyhexamethylene biguanides towards cells was also enhanced in the rough strains. Binding affinity was, in all cases, significantly reduced in the presence of magnesium and suggested a mechanism of self-promoted uptake for these biocides, facilitated through core lipopolysaccharide.

Biguanides↗

Synergism within polyhexamethylene biguanide biocide formulations.

Polyhexamethylene biguanides (PHMB) are mixtures of polymeric biguanides with an average polymer length (n) of 5, but containing high (n greater than 15, mol. wt 3300) and low molecular weight material (n = 2, mol. wt 400). Studies involving discrete molecular weight fractions of PHMB have shown that antimicrobial activity of PHMB increases with increasing polymer length. Cell suspensions which had not been subjected to centrifugation and/or washing during their preparation were employed. Whilst activity was still observed to increase with n, the trend was much reduced as n exceeded six. Centrifugation and washing of cells markedly increased the activity of high but not low molecular weight materials and corresponded to losses upon centrifugation of envelope lipopolysaccharide (LPS). Such envelope LPS represented high affinity binding sites on the surfaces of the cells. Combinations of various molecular weight fractions of PHMB were evaluated against filter-washed cells and revealed a profound synergy between extremes of polymer length.

Adsorption↗

Possible involvement of the division cycle in dispersal of Escherichia coli from biofilms.

Growth rate control of adherent, sessile populations was achieved by the controlled perfusion of membrane-associated bacterial biofilms by the method of Gilbert et al. (P. Gilbert, D. G. Allison, D. J. Evans, P. S. Handley, and M. R. W. Brown, Appl. Environ. Microbiol. 55:1308-1311, 1989). Changes in cell surface hydrophobicity were evaluated with respect to growth rate for such sessile Escherichia coli cells and compared with those of suspended (planktonic) populations grown in a chemostat. Newly formed daughter cells shed at the various growth rates from the biofilm during its growth and development were also included in the study. Surface hydrophobicity decreased with growth rate similarly for both planktonic and sessile E. coli; no significant differences were noted between the two. Daughter cells dislodged from the biofilm, however, were significantly more hydrophilic than those remaining, indicating that hydrophobicity changed during the division cycle. Our data support the hypothesis that dispersal of cells from adhesive biofilms and recolonization of new surfaces reflect cell-cycle-mediated events.

Bacterial Adhesion↗

Combination therapy for penile giant Buschke-Löwenstein condyloma.

The case of a 25-year-old patient who underwent circumcision and Neodymium-YAG laser treatment for giant condylomata acuminata of the penis is presented. Two cycles of interferon therapy were administered postoperatively, each comprising beta-interferons and recombinant gamma-interferons. This combination therapy provided an excellent cosmetic and functional result and the patient remains disease-free 15 months following surgery.

Adult↗

Production of monoclonal antibodies against principal cells of the renal collecting duct by in vitro immunization with unsolubilized antigens.

We report the production of monoclonal antibodies (MAb) by an in vitro technique which react with principal cells of the renal collecting duct. Spleen cells were directly simulated in vitro with unsolubilized antigens, i.e., by direct contact with the apical site of cultivated principal cells or by contact with cell fragments. Out of several others two antibodies, IV1 and IV2, were selected, which specifically reacted with the principal cells of the collecting duct. MAbIV1 also reacted with Type A intercalated cells, indicating the existence of a common antigen in the apical membrane of both cell types. Type B intercalated cells were consistently unreactive. All other parts of the uriniferous tubule were also unreactive. In Western blot analysis MAb IV1 showed immunoreactivity with a 40 KD and a 43 KD antigen. Our experiments demonstrate the possibility of producing antibodies against unsolubilized antigens by a simple in vitro technique. The activity of particular lymphocyte in this in vitro system is shown by the specificity of the antibodies.

Animals↗