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Biomedical subjects

B Sugarman

Publications and source records attributed to B Sugarman.

At least 19 recordsLinked to original sources
PubMed2001

Re-engineering adenovirus regulatory pathways to enhance oncolytic specificity and efficacy.

Replicating adenoviruses may prove to be effective anticancer agents if they can be engineered to selectively destroy tumor cells. We have constructed a virus (01/PEME) containing a novel regulatory circuit in which p53-dependent expression of an antagonist of the E2F transcription factor inhibits viral replication in normal cells. In tumor cells, however, the combination of p53 pathway defects and deregulated E2F allows replication of 01/PEME at near wild-type levels. The re-engineered virus also showed significantly enhanced efficacy compared with extensively studied E1b-deleted viruses such as dl1520 in human xenograft tumor models.

Adenoviridae↗
PubMed1998

Comparison of flow cytometry and laser scanning cytometry for the intracellular evaluation of adenoviral infectivity and p53 protein expression in gene therapy.

The determination of recombinant adenoviral (rAd) infectivity and p53 protein expression is important for the evaluation of rAd vectors containing the p53 gene (rAd-CMV-p53) for gene therapy. We have previously reported that rAd5-CMV-p53 vectors can be assessed for infectivity and concomitant p53 protein expression in single- and two-color assays using intracellular staining methodology and flow cytometric analysis. We have compared the flow cytometry-based assays for rAd infectivity (hexon protein) and p53 protein expression with the new slide-based laser scanning cytometry (LSC). We report that LSC analysis of rAd-CMV-p53-infected human 293 cells correlated very well with flow cytometric analysis across a wide range of viral infectivity for both infectivity assessment (r2 = 0.97) and p53 protein expression (r2 = 0.96). Absolute values for infective titer and p53 protein expression titer from an rAd5-CMV-p53 production batch were similar and within experimental error with the two different analytical methods. Finally, bivariate format analysis of rAd-CMV-p53-infected cells revealed comparable results between LSC and flow cytometric analysis. LSC is a reliable and useful tool for the intracellular staining for adenoviral hexon protein expression for determining infectivity and for p53 protein expression from an expressed p53 transgene.

Adenoviruses, Human↗
PubMed1991

Chemorepulsion of trichomonads by products of neutrophil oxidative metabolism.

To determine whether secreted neutrophil products affect the migration of motile microorganisms such as Trichomonas vaginalis, stimulated human neutrophils and cell-free oxygen metabolites were used as stimuli in a multiwell filter chemotaxis assay using tritiated T. vaginalis. When stimulated neutrophils were present on the opposite side of the filter, migration of T. vaginalis into the filter was significantly diminished, and this reduction varied with the dose of neutrophil stimulus. The reduction of movement was abrogated by the addition of catalase and superoxide dismutase to scavenge oxygen metabolites. Studies with cell-free hydrogen peroxide or hypochlorite preparations indicated that the reduction in trichomonal trapping in the filter was due to chemorepulsion and not to a nonspecific decrease in motility or adherence. These findings suggest that active migration away from neutrophil products might be a means by which trichomonads avoid the microbicidal functions of host phagocytes.

Animals↗
PubMed1990

Oestrogen binding by and effect of oestrogen on trichomonads and bacteria.

It has been shown previously that Trichomonas vaginalis, a common protozoan pathogen of the female genito-urinary tract, has binding sites for oestrogen and that its growth, adherence and chemotaxis are altered after exposure to physiological concentrations of oestrogens. Two other species of trichomonad showed no physiological response to oestrogens but did have high affinity oestrogen binding with low binding capacity. To determine whether oestrogen binding sites occur in other pathogenic micro-organisms, these studies with eukaryotic pathogens were extended to prokaryotic bacteria. Numerous bacteria previously considered to be oestrogen responsive, other species of the same genera, and control bacteria (not considered oestrogen responsive) were examined. High affinity protein-containing oestrogen binding sites were demonstrated in several bacterial genera. Direct oestrogenic effects on micro-organisms, as well as the traditional oestrogenic effects on host cells, may explain why certain infections are more common or more severe after exposure to oestrogen.

Animals↗
PubMed1990

Antipyresis and fever.

While understanding of the mechanisms of fever has progressed in recent years, much uncertainty remains as to whether fever in itself (as distinct from its cause) is beneficial or harmful, and what circumstances warrant antipyretic therapy. This review was designed to identify studies providing information on the effects of fever and of pharmacologic and physical therapy. Fever or analogous behavioral thermal upregulation apparently has positive effects on defense against infection in some animal models. Retrospective studies in humans suggest that failure to mount a febrile response is associated with poor outcome in certain infections but do not establish a causal relationship. Induction of fever apparently had therapeutic value in infections such as syphilis before specific antimicrobials were developed. Fever may have deleterious effects in the context of borderline cardiovascular or neurologic function or pregnancy, but data in most instances cannot separate effects of fever per se from that of underlying disease. Antipyretic drugs are effective in diminishing fever, but they have significant side effects and may suppress signs of ongoing infection. Physical cooling is important when physiologic thermoregulatory mechanisms are overwhelmed, but may sometimes increase discomfort and metabolic stress in fever. Antipyretic therapy should not be instituted routinely for every febrile episode but should be based on evaluation of relative risks in the individual case and reassessed if anticipated benefits are not achieved.

Animals↗
PubMed1989

The extended-spectrum penicillins: microbiologic, utilization, and cost review in a community hospital.

The extended-spectrum penicillins have a similar spectrum of activity and clinical efficacy. The newer acylaminopenicillins (azlocillin, mezlocillin, piperacillin) offer several potential therapeutic advantages over the carboxypenicillins (carbenicillin, ticarcillin), but they are more expensive per gram. Literature reviews of these penicillins suggest that individual hospital susceptibility patterns and cost should guide selection of the most appropriate antibiotic for formulary addition. Consequently, the authors performed a microbiologic, utilization, and cost review of these antibiotics in a community hospital. From this hospital and literature review, the authors were able to make the following conclusions: (1) the newer acylaminopenicillins exhibited similar activity against common clinical pathogens and were microbiologically more active than the carboxypenicillins; (2) none of these antibiotics used alone appears adequate for empiric treatment of serious systemic gram-negative bacillary infections; (3) the extended-spectrum penicillins were prescribed in a similar fashion and usually in conjunction with an aminoglycoside; and (4) significant cost savings can be realized when less expensive drugs are used. The authors found only minor differences in microbiologic activity and clinical use among the newer extended-spectrum penicillins. Therefore, they recommend the least expensive drug for routine use in the hospital.

Ampicillin↗
PubMed1989

Infections associated with prosthetic devices: magnitude of the problem.

The number and diversity of prosthetic devices inserted into patients continue to increase each year. Despite technological advances in the design and manufacture of prostheses and improved surgical techniques, infection remains a serious and potentially fatal complication. Although the incidence of serious infections remains low (averaging a few per cent for totally implanted devices), the consequences of an infected prosthesis can be disastrous. The incidence of infections related to temporary or partially implanted devices is even higher than for prostheses completely covered by the skin. In addition to excess morbidity and occasionally mortality, prosthesis-related infections add to the costs of medical care and to prolonged hospitalization. the magnitude of the problem is greatly underappreciated, in part due to the care of such infections on a piecemeal basis by numerous and diverse health care specialists.

Bacterial Infections↗
PubMed1988

Infections in prosthetic devices.

Infection in prosthetic devices is a rare but potentially serious complication of prosthesis implant surgery. Infections associated with a variety of permanently implanted devices are reviewed in the context of recent knowledge of the host-prosthesis interaction.

Anti-Bacterial Agents↗
PubMed1988

The effect of hormones on Trichomonas vaginalis.

The hormonal milieu can alter susceptibility to infection. The effect of hormones on Trichomonas vaginalis was studied utilizing axenically cultured clinical isolates. Oestrogens, in physiological concentrations, decreased the growth of the organisms and their attachment to mammalian cells in vitro, and acted as a chemorepellent. The specificity of these effects was verified by their being blocked with anti-oestrogens, by the dose- and time-dependency of the responses, and by the lack of effect with other hormones. These results suggest that oestrogens may decrease the virulence of T. vaginalis; however, interactions between oestrogens and mammalian cells may promote the development of infection. Thus complicated interactions between hormones, micro-organisms and mammalian cells must determine whether exposure to oestrogens predisposes to or prevents the development of infection.

Animals↗
PubMed1988

Effects of antimicrobial agents on growth and chemotaxis of Trichomonas vaginalis.

The motility of viable Trichomonas vaginalis organisms is readily demonstrable in a clinical wet mount or cultured specimens. We attempted to determine whether migration is a dynamic process such that the organisms move to avoid exposure to toxic antimicrobial agents. With the use of axenic cultures of T. vaginalis that were radiolabeled and assayed for chemotaxis in plastic multiwelled plates with a membrane filter inserted to trap organisms, the response of clinical isolates to various antimicrobial agents was studied. Chemotaxis was readily demonstrable and dependent upon factors including time of incubation, media used, and viscosity of media. Nitroimidazoles (e.g., metronidazole) which readily inhibited the growth of these organisms also caused significant chemorepulsion after minutes of exposure. The antifungal imidazoles ketoconazole and miconazole inhibited growth nearly as readily and caused chemorepulsion, but to a lesser degree. The spermicide Nonoxynol-9 also inhibited growth and caused significant chemorepulsion. The minimal concentrations of many compounds which inhibited growth were very similar to those which caused significant chemorepulsion. Imidazole and antibiotics (e.g., penicillin) which did not inhibit growth did not induce any chemotactic effects. Chemotaxis of T. vaginalis is an active and dynamic process, and the organisms display chemorepulsion shortly after exposure to toxic antimicrobial agents, well before toxicity can be demonstrated.

Animals↗
PubMed1987

Gastrointestinal zoonoses.

Infectious gastrointestinal diseases affect man and animals throughout the world. Certain etiologic agents (for example, Salmonella spp., Campylobacter jejuni, Yersinia enterocolitica, Cryptosporidia, Strongyloides stercoralis, Echinococcus granulosa) seem to have the potential to be transmitted from pets to people, causing severe disease in the latter. Other agents seem unlikely to be transmitted but may have the potential to be zoonoses. This article discusses proved, suspected, and possible zoonotic agents that may originate from the gastrointestinal tract of dogs and cats.

Animals↗
PubMed1987

Manifestations of sepsis.

The clinical manifestations of sepsis may be flagrant or subtle. Awareness of the signs and symptoms of sepsis allows early recognition and prompt, appropriate management. The clinical presentation, relative frequency, and current pathophysiologic understanding of the manifestations of sepsis are reviewed. Special emphasis is placed on the cardiopulmonary manifestations, which are examined in a temporal sequence of preshock, early shock, and late shock states. While therapy for the underlying infection (such as antibiotics and drainage of abscesses) is often sufficient, therapy for the specific manifestations of sepsis may also be necessary. Guidelines for therapy for these manifestations of sepsis are given.

Bacterial Infections↗
PubMed1987

Pressure sores and underlying bone infection.

Pressure sores are a serious complication of hospitalized and chronically ill patients. Evaluation for underlying bone infection can be made difficult by radiographic, nuclear imaging, and soft-tissue culture studies that are abnormal and suggest the presence of bone infection, when no infection is present. Evaluation by bone biopsy with histologic and microbiological studies can accurately and promptly diagnose whether bone infection is present. This allows appropriate treatment when infection is present, and prevents unneeded and potentially toxic antibiotic therapy when preliminary studies incorrectly suggest that infection is present.

Biopsy↗
PubMed1986

Infections and prosthetic devices.

Hundreds of thousands of people have temporary or permanent prosthetic devices inserted each year in the United States. Infection rates associated with these devices vary depending upon numerous factors; however, overall, several percent of these devices become associated with infection. Diagnosis of these infections can be complicated by underlying disease, surgery, or the prosthesis itself, making it difficult to ascertain whether abnormalities of routine diagnostic studies are caused by infection. Specific diagnostic tests are usually required to confirm the presence of infection and identify the causative organism. The frequent isolation of skin organisms (such as Staphylococcus epidermidis) as the pathogen can also cause confusion as to whether the culture was contaminated. Fortunately, treatment of these infections is usually successful, although removal of the prosthetic device is often necessary. Recent laboratory and clinical studies that demonstrate various steps in the development of these infections and their response to treatment will help to better determine the optimal prevention, diagnosis, and treatment of these infections.

Anti-Bacterial Agents↗
PubMed1986

Coming to terms with management.

This article postulates that clinicians need to understand the nature of the management role in substance abuse agencies, even if they have no aspirations to occupy a management role, because it profoundly affects their conditions of work as clinicians. The article aims to demystify the management role, breaking it down into three major areas of related functions: clinical management, business management, and agency management. A crucial and much misunderstood aspect of the management role, especially at the agency level, is the dimension of power or the management of organizational politics. Lastly we note several advantages that the former clinician has as a manager.

Ambulatory Care Facilities↗
PubMed1986

Estrogens and Chlamydia trachomatis.

Isolates of Chlamydia trachomatis were inoculated in nonreplicating McCoy cells and incubated for 48 hr with various concentrations of hormones. Only the estrogens, particularly 17-beta-estradiol, had an affect on the subsequent infection of the McCoy cells by the Chlamydia. Exposure to 2-4 ng/ml (10(-8) M) estradiol during inoculation and incubation was associated with no change in the initial binding of Chlamydia to McCoy cells, but significantly more (about twofold) Chlamydia inclusions in the McCoy cells after 48 hr incubation. This effect was dose dependent, could be blocked with anti-estrogens, and also occurred with replicating McCoy cells. Localization studies suggest that this effect on the infectivity of Chlamydia trachomatis is dependent upon initial interactions of estrogens with McCoy cells. Both light microscopy and electron microscopy of the McCoy (fibroblast) cells showed no morphological changes after exposure to the estrogens under the incubation conditions employed in these studies. Estrogens may modify host susceptibility to Chlamydia infections in a manner independent of morphological changes in mammalian cells.

Animals↗