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Biomedical subjects

M Ross

Publications and source records attributed to M Ross.

At least 37 records · Page 2Linked to original sources

Development of a new in vitro model for the study of benign prostatic hyperplasia.

BACKGROUND: The search for novel agents for the treatment of the lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) is dependent on an increased understanding of the pathophysiology of the disease. Unfortunately, in vitro and animal models have been of limited value. METHODS: This article describes a novel model system in which the interactions of the stromal and epithelial components of the prostate gland can be determined. RESULTS: The coculture system provides a simple model of the cellular interactions occurring in the adult human prostate. CONCLUSIONS: This coculture system could potentially be used to determine the precise molecular site of action of agents such as terazosin on prostatic apoptosis.

Cell Differentiation↗

Analysis of lung surfactant model systems with time-of-flight secondary ion mass spectrometry.

An often-used model lung surfactant containing dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), and the surfactant protein C (SP-C) was analyzed as Langmuir-Blodgett film by spatially resolved time-of-flight secondary ion mass spectrometry (TOF-SIMS) to directly visualize the formation and composition of domains. Binary lipid and lipid/SP-C systems were probed for comparison. TOF-SIMS spectra revealed positive secondary ions (SI) characteristic for DPPC and SP-C, but not for DPPG. SI mapping results in images with domain structures in DPPC/DPPG and DPPG/SP-C, but not in DPPC/SP-C films. We are able to distinguish between the fluid and condensed areas probably due to a matrix effect. These findings correspond with other imaging techniques, fluorescence light microscopy (FLM), scanning force microscopy (SFM), and silver decoration. The ternary mixture DPPC/DPPG/SP-C transferred from the collapse region exhibited SP-C-rich domains surrounding pure lipid areas. The results obtained are in full accordance with our earlier SFM picture of layered protrusions that serve as a compressed reservoir for surfactant material during expansion. Our study demonstrates once more that SP-C plays a unique role in the respiration process.

1,2-Dipalmitoylphosphatidylcholine↗

Formation of three-dimensional protein-lipid aggregates in monolayer films induced by surfactant protein B.

This study focuses on the structural organization of surfactant protein B (SP-B) containing lipid monolayers. The artificial system is composed of the saturated phospholipids dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) in a molar ratio of 4:1 with 0.2 mol% SP-B. The different "squeeze-out" structures of SP-B were visualized by scanning probe microscopy and compared with structures formed by SP-C. Particularly, the morphology and material properties of mixed monolayers containing 0.2 mol% SP-B in a wide pressure range of 10 to 54 mN/m were investigated revealing that filamentous domain boundaries occur at intermediate surface pressure (15-30 mN/m), while disc-like protrusions prevail at elevated pressure (50-54 mN/m). In contrast, SP-C containing lipid monolayers exhibit large flat protrusions composed of stacked bilayers in the plateau region (app. 52 mN/m) of the pressure-area isotherm. By using different scanning probe techniques (lateral force microscopy, force modulation, phase imaging) it was shown that SP-B is dissolved in the liquid expanded rather than in the liquid condensed phase of the monolayer. Although artificial, the investigation of this system contributes to further understanding of the function of lung surfactant in the alveolus.

1,2-Dipalmitoylphosphatidylcholine↗

The frequency of temporal-self and social comparisons in people's personal appraisals.

Although past literature emphasizes the importance of social comparisons, in this study it was predicted that participants would often mention temporal comparisons in their self-descriptions. The first 3 studies revealed that participants report as many or more temporal-past comparisons than social comparisons. It was predicted that people would particularly favor temporal-past comparisons when they are interested in enhancing themselves. Temporal-past comparisons are gratifying, because they tend to indicate improvement over time. Social comparisons may be preferred when people are motivated to evaluate themselves accurately. These predictions were supported when self-evaluation and self-enhancement goals were explicitly manipulated (Study 4) or primed (Study 5).

Female↗

People focus on optimistic scenarios and disregard pessimistic scenarios while predicting task completion times.

Task completion plans normally resemble best-case scenarios and yield overly optimistic predictions of completion times. The authors induced participants to generate more pessimistic scenarios and examined completion predictions. Participants described a pessimistic scenario of task completion either alone or with an optimistic scenario. Pessimistic scenarios did not affect predictions or accuracy and were consistently rated less plausible than optimistic scenarios (Experiments 1-3). Experiment 4 independently manipulated scenario plausibility and optimism. Plausibility moderated the impact of optimistic, but not pessimistic, scenarios. Experiment 5 supported a motivational explanation of the tendency to disregard pessimistic scenarios regardless of their plausibility. People took pessimistic scenarios into account when predicting someone else's completion times. The authors conclude that pessimistic-scenario generation may not be an effective debiasing technique for personal predictions.

Affect↗

The selectivity and specificity of the actions of the lipido-sterolic extract of Serenoa repens (Permixon) on the prostate.

PURPOSE: To investigate the effects of the phytotherapeutic agent, Permixon(R), on primary cultures of fibroblast and epithelial cells from the prostate, epididymis, testes, kidney, skin and breast and to determine the selectivity and specificity of the action of the drug. MATERIALS AND METHODS: All primary cultures were examined by electron microscopy before and following treatment with Permixon(R) (10 microg./ml.). In addition the apoptotic index was assessed by flow cytometry employing propidium iodide as a fluorophore. The impact of the drug on 5alpha-reductase (5alphaR) isoenzymes was also tested utilizing a pH specific assay. RESULTS: There were changes in the morphology of prostate cells after treatment including accumulation of lipid in the cytoplasm and damage to the nuclear and mitochondrial membranes; no similar changes were observed in other cells. Permixon(R) increased the apoptotic index for prostate epithelial cells by 35% and 12% in the prostate stromal/fibroblast. A lesser apoptotic effect was demonstrated in skin fibroblast (3%) whereas none of the other primary cultures showed any increase in apoptosis when compared with the controls. Permixon(R) was also an effective inhibitor of both 5alphaR type I and II isoenzymes in prostate cells, but other cells showed no inhibition of 5alphaR activity following treatment with the plant extract. CONCLUSIONS: This investigation demonstrated the selectivity of the action of Permixon(R) for prostate cells. The morphological changes in the prostate are accompanied by an increase in the apoptotic index along with an inhibition in the activity of the nuclear membrane bound 5alphaR isoenzymes. No similar changes were observed in any of the other cells under investigation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Perceived compliance with AZT dosing among a sample of African-American drug users.

The purpose of this report was to present findings from a pilot study conducted to explore the associations between sociodemographic, drug use, and health belief factors and perceived compliance with zidovudine (AZT) among African-American drug users. Data were collected in Washington, DC, USA from individuals who were African-American; were recent or current drug injectors or crack smokers; were HIV-seropositive, and were receiving treatment for HIV infection. Participants were recruited through local organizations that provide services to HIV-infected persons. Participants were interviewed using a questionnaire that solicited sociodemographic, lifetime and current drug use, current sexual behaviours, health status, HIV and drug treatment history, and health belief data. Analyses were limited to individuals currently using an illicit substance and who had received AZT during their medical treatment. Parametric (Pearson's r) and nonparametric (Spearman's rho) statistics were used to assess correlations between perceived compliance with AZT dosing and independent variables. As the study was intended to be both descriptive and exploratory, the level of statistical significance was set at 0.10, rather than the customary 0.05. Antiretroviral medications recognized and recalled by participants are presented. The most commonly recalled medication was AZT. Slightly less than one-third of participants reported being completely compliant with an AZT regimen. Perceived compliance was found to be negatively associated with 5 variables: age, homelessness, number of injections in the previous 30 days, trading sex for drugs, and the perception that AIDS is no longer a serious disease since the development of new antiretroviral medications. Intensity of feelings of joy, fear, and the belief that taking more anti-HIV medications would result in better health were found to be positively correlated. Bivariate associations between perceived compliance and sociodemographic, drug use, sexual behaviour, and health belief variables suggest further avenues of study and potential points for intervention to increase compliance with antiretroviral medications among racial/ethnic minority drug users receiving treatment for HIV infection.

Adolescent↗

Challenges and directions for Medicare ESRD payment policy.

Since the inception of the ESRD program in 1973, Medicare has been challenged to provide access to high-quality care to beneficiaries with ESRD while trying to contain program payments. Despite implementing policies to control the growth in spending for outpatient dialysis and shifting the risk of certain ESRD beneficiaries to private payers, annual ESRD program payments have grown faster than overall Medicare spending. Some stakeholders contend that these policies have adversely affected beneficiaries' access to high-quality care. Refining the payment systems for caring for beneficiaries with ESRD in traditional Medicare and managed care plans may provide some respite to the growth in ESRD program spending in the short-term. In the long run, ESRD program spending may not be effectively controlled until changes are made in the delivery of health care services to this population.

Humans↗

Serenoa repens (Permixon): a 5alpha-reductase types I and II inhibitor-new evidence in a coculture model of BPH.

BACKGROUND: The aim of this study was to determine the effect of the phytotherapeutic agent, Permixon, on a novel coculture model of benign prostatic hyperplasia (BPH) in an effort to better understand the mode of action of the drug in vivo. METHODS: The effect of Permixon, at the calculated therapeutic concentration, on the activity of 5alpha-reductase isoenzymes was evaluated utilizing a pH-specific assay. Prostate-specific antigen (PSA) secretions into the medium were measured in the presence and absence of Permixon and quantified by an ELISA assay. The morphological patterns before and following Permixon treatment were also examined by electron microscopy. All results were compared to controls. RESULTS: Permixon at a concentration of 10 micrograms/ml (calculated plasma concentration in patient receiving recommended therapeutic dosage) was shown to be an effective inhibitor of both 5alpha-reductase types I and II isoenzymes without influencing the secretion of PSA by the epithelial cells, even after stimulation with testosterone. The morphology of Permixon-treated cells was found to be markedly different from that of untreated controls. Cells which had been treated with the drug demonstrated extensive accumulation of lipids in the cytoplasm and widespread damage of intracellular membranes, including mitochondrial and nuclear membranes. CONCLUSIONS: Permixon is an effective dual inhibitor of 5alpha-reductase isoenzyme activities in the prostate. Unlike other 5alpha-reductase inhibitors, Permixon induces this effect without interfering with the cells' capacity to secrete PSA, thus permitting the continued use of PSA measurements for prostate cancer screening.

5-alpha Reductase Inhibitors↗

Organophosphate skin decontamination using immobilized enzymes.

We previously demonstrated that a combination of cholinesterase (ChE) pre-treatment with an oxime is an effective measure against soman and sarin. We describe here a novel approach for the preparation of covalently linked ChEs which are immobilized to a polyurethane matrix. Such preparation of ChE-sponges enhances the stability and usefulness of the enzymes in non-physiological environments. The ChE-sponges, which can be molded to any form, can effectively be used to remove and decontaminate organophosphates (OPs) from surfaces, biological (skin or wounds) or otherwise (clothing or sensitive medical equipment), or the environment. The ChE-sponges retained their catalytic activity under conditions of temperature, time, and drying where the native soluble enzyme would rapidly denature, and can be reused in conjunction with oximes many times. The ChE-sponge in the presence of oxime repeatedly detoxified OPs such as DFP or MEPQ. These developments in ChE technology have extended the applicability of OP scavengers from in vivo protection, to a variety of external detoxification and decontamination schemes. In addition to treatment of OP-contaminated soldiers, the ChE-sponge could protect medical personnel from secondary contamination while attending chemical casualties, and civilians exposed to pesticides or highly toxic nerve agents such as sarin.

Cholinesterase Inhibitors↗

Phase II studies with DaunoXome in patients with nonresectable hepatocellular carcinoma: clinical and pharmacokinetic outcomes.

A total of 14 Chinese patients with inoperable hepatocellular carcinoma received a liposomal formulation of daunorubicin (DaunoXome) at a dose equivalent to 100 mg/m2 of the free drug every 3 weeks. Altogether, 12 patients were assessable for response; 2 patients had stable disease for 8 weeks, but all eventually developed progressive disease and there was no responder. The drug was well tolerated, with no evidence of cardiac toxicity being observed. Deterioration of liver-function tests was attributed to progressive tumors in the terminal stage of the disease. Pharmacokinetics studies revealed a biexponential decay for daunorubicin in association with mean initial and terminal half-lives of 1.8 and 7.4 h, respectively, and a mean total clearance of 15.0+/-5.5 ml/min. The AUC ratio between the metabolite daunorubicinol and daunorubicin was 0.07. These data differ markedly from the pharmacokinetics of the free drug.

Adult↗

Cervical electromyographic activity during low-speed rear impact.

Whiplash motion of the neck is characterized by having an extension-flexion motion of the neck. It has been previously assumed that muscles do not play a role in the injury. Eight healthy males were seated in a car seat mounted on a sled. The sled was accelerated by a spring mechanism. Muscle electromyographic (EMG) activity was measured by wire electrodes in semi-spinalis capitis, splenius capitis, and levator scapulae. Surface EMG activity was measured over trapezius and sternocleidomastoideus. Wavelet analysis was used to establish the onset of muscle activity with respect to sled movement. Shorter reaction times were found to be as low as 13.2 ms from head acceleration and 65.6 ms from sled acceleration. Thus the muscles could influence the injury pattern. It is of interest that clinical symptoms are often attributed to muscle tendon injuries.

Acceleration↗

Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prevention of acute graft-vs.-host disease: effect on chronic graft-vs.-host disease and long-term survival.

Graft-vs.-host disease (GVHD) is a major predictor of outcome following allogeneic bone marrow transplantation (BMT). For patients alive at day 100 after BMT, the presence or absence of chronic GVHD is one of the most important determinants of survival and quality of life. We wished to determine the effects on chronic GVHD of two regimens used for the prophylaxis of acute GVHD: cyclosporine, methotrexate, and prednisone (CSA/MTX/PSE) and cyclosporine and prednisone (CSA/PSE). One hundred forty-nine evaluable patients were entered into the acute GVHD study. As of 31 March 1997, 63 months after the last patient underwent BMT, the median survival time was 4.5 years (range 0.09-9.9). The incidence of chronic GVHD was independent of the prophylactic regimen (55 vs. 54%), and extensive chronic GVHD occurred in 25 and 24% of patients receiving CSA/MTX/PSE and CSA/PSE, respectively. Of note, the median Karnofsky performance status of both groups was 100% (range 70-100%), reflecting the low incidence of extensive chronic GVHD. Survival rates free of chronic GVHD were 52 vs. 42% (p = 0.29) for patients receiving CSA/MTX/PSE vs. CSA/PSE. The incidence of relapse was also similar in both groups of patients. These data suggest that the combinations of CSA/MTX/PSE and CSA/PSE result in comparable chronic GVHD-free survival without an increase in leukemic relapse.

Acute Disease↗

Post-mortem incidental finding of cytomegalovirus oophoritis after an allogeneic stem cell transplant.

Cytomegalovirus (CMV) disease is a common and serious complication of allogeneic stem cell transplantation (SCT). Its two most frequent manifestations are interstitial pneumonitis and gastroenteritis. We describe here the first reported case of CMV ovarian infection in an allo-SCT recipient. This patient was included in a clinical trial of high-dose chemotherapy (HDCT) with HLA-matched peripheral SCT for metastatic breast cancer. She expired 53 days after transplantation from organ failure unrelated to her CMV oophoritis.

Antineoplastic Combined Chemotherapy Protocols↗

High-dose therapy with autologous hematopoietic cell support as salvage treatment for patients with breast cancer who have relapsed after previous high-dose chemotherapy.

Twenty-six patients with breast cancer who had relapsed after previously receiving high-dose chemotherapy and autologous hematopoietic cell support received a second course of high-dose cytoreductive therapy and autologous hematopoietic cell support as salvage therapy. Several different high-dose therapy regimens were employed for the second transplant, including a radiolabeled immunoconjugate. Two patients died of treatment-related complications. The remaining 24 patients relapsed a median of 126 (range 22-635) days after salvage transplant. All have since died. The median survival after salvage transplant was 362 (range 31-931) days. We conclude that second courses of high-dose therapy as salvage treatment are generally well-tolerated but their efficacy is modest. Alternative treatment strategies are needed for these patients.

Adult↗