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Biomedical subjects

N Greenberg

Publications and source records attributed to N Greenberg.

At least 19 recordsLinked to original sources
PubMed2006

Medical downgrading, self-perception of health, and psychological symptoms in the British Armed Forces.

OBJECTIVE: To investigate the contribution of psychological symptoms to limited employability for medical reasons in the British Armed Forces. METHODS: A sample of 4500 military personnel was randomly selected to receive either a full or an abridged questionnaire. The questionnaires asked whether the participant was medically downgraded and if yes, the reason for it. The full questionnaire included the General Health Questionnaire-12 (GHQ-12), the post-traumatic stress disorder (PTSD) checklist, 15 symptoms to assess somatisation, and selected items of the quality of life SF-36 questionnaire. The abridged questionnaire included the GHQ-4, a 14 item PTSD checklist, five symptoms, and the item on self-perception of health from the SF-36. Subjects above a threshold score for GHQ, PTSD, and symptoms were considered to have psychological symptoms. RESULTS: 12.4% of the participants were medically downgraded. The majority (70.4%) had social or work limitations. Medically downgraded personnel had higher odds ratios in comparison to non-downgraded personnel for psychological distress 1.84 (95% CI 1.43 to 2.37), PTSD 3.06 (95% CI 1.82 to 5.15), and number of symptoms 2.37 (95% CI 2.37 1.62 to 3.47). GHQ, PTSD, and symptoms scores were mainly, but not exclusively, related to chronic physical injury. CONCLUSIONS: Psychological symptoms are common among medically downgraded personnel. Although the mechanisms involved are unclear, tackling issues of psychological symptoms among these subjects could contribute to faster restitution to full employability in the Armed Forces.

Acute Disease↗
PubMed2005

Caseinoglycomacropeptide inhibits adhesion of pathogenic Escherichia coli strains to human cells in culture.

Caseinoglycomacropeptide (CGMP) derived from kappa-casein was investigated for its ability to inhibit the adhesion of 3 strains of verotoxigenic Escherichia coli (VTEC) and 3 strains of enteropathogenic Escherichia coli (EPEC) to human HT29 tissue cell cultures. Effects on adhesion of Desulfovibrio desulfuricans, Lactobacillus pentosus, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus gasseri were also investigated. Generally, CGMP exerted effective anti-adhesive properties at a dose of 2.5 mg/mL, albeit with a high degree of strain specificity. The CGMP reduced adhesion of VTEC strains to <50% of the control and reduced adhesion of EPEC strains to between 80 and 10% of the control. The CGMP also reduced the adhesion of L. pentosus and L. casei to 44 and 42%, respectively. A slight but significant reduction of L. acidophilus, to 81%, was observed, but no significant effects were detected with either Dsv. desulfuricans or L. gasseri. Further investigation of the dose response relationships with the E. coli strains gave IC50 values ranging between 0.12 and 1.06 mg/mL.

Adenocarcinoma↗
PubMed2003

Temporal patterns of limbic monoamine and plasma corticosterone response during social stress.

Dominant and subordinate males respond differently to the stress of social interaction. After an hour of social interaction, subordinate male Anolis carolinensis have elevated serotonergic activity in hippocampus, but dominant males do not. In other species, and using other stressors, the activation of hippocampal serotonergic activity is much more rapid than one hour. To elucidate early stress responsiveness, adult male A. carolinensis were divided into four groups: isolated controls, and pairs of males sampled after 10, 20 or 40 minutes of aggressive interaction. Development of dominant-subordinate relationships was determined by behavior and by the celerity of eyespot darkening. Serotonergic activity in the hippocampus, nucleus accumbens and amygdala was elevated rapidly and equally in both dominant and subordinate males, as were plasma corticosterone concentrations. Serotonergic activity remained elevated through 40 minutes in hippocampus and nucleus accumbens. Only subordinate males had elevated corticosterone levels at 40 minutes. Social status does not impede socially induced stress responses. Rather, rapid regulation of serotonergic stress responses appears to be a mediating factor in determining both behavioral output and social status. Temporal expressions of monoaminergic and endocrine stress responses are distinctive between males of dominant and subordinate social status. Such temporal patterns of transmitter and glucocorticoid activity may reflect neurocircuitry adaptations that result in behavior modified to fit social status.

Aggression↗
PubMed2003

Peer-group risk assessment: a post-traumatic management strategy for hierarchical organizations.

BACKGROUND: Organizations have moral and legal duties to consider the psychological needs of their workforce following exposure to potentially traumatic events related to the workplace. Additionally, it makes economic sense to avoid loss of valuable personnel to the effects of psychological trauma. There have been attempts to provide a range of psychological interventions for staff after exposure to potentially traumatizing events, but recent evidence-based medicine publications have questioned their effectiveness and, indeed, some studies show that single-session psychological debriefings may be harmful. AIM: This paper presents a post-traumatic management strategy based upon peer-group risk assessment which was developed by the British military and is in use with other hierarchical organizations. The presented model keeps employees functioning after traumatic events and provides support and education to those who require it. Additionally, the strategy aims to identify those who are unable to cope after potentially traumatizing events and aims to refer them for early intervention, which has been shown to be of benefit.

Adult↗
PubMed2001

Haploinsufficiency of the Pten tumor suppressor gene promotes prostate cancer progression.

The PTEN gene encodes a lipid phosphatase that negatively regulates the phosphatidylinositol 3-kinase pathway and is inactivated in a wide variety of malignant neoplasms. High rates of loss of heterozygosity are observed at the 10q23.3 region containing the human PTEN gene in prostate cancer and other human malignancies, but the demonstrated rate of biallelic inactivation of the PTEN gene by mutation or homozygous deletion is significantly lower than the rate of loss of heterozygosity. The transgenic adenocarcinoma of mouse prostate model is a well characterized animal model of prostate cancer. Analysis of prostate cancer progression in transgenic adenocarcinoma of mouse prostate mice bred to Pten(+/-) heterozygous mice, coupled with analysis of the Pten gene and protein in the resulting tumors, reveals that haploinsufficiency of the Pten gene promotes the progression of prostate cancer in this model system. This observation provides a potential explanation for the discordance in rates of loss of heterozygosity at 10q23 and biallelic PTEN inactivation observed in prostate cancer and many human malignancies.

Animals↗
PubMed2001

Adenovirus-mediated transfer of inducible caspases: a novel "death switch" gene therapeutic approach to prostate cancer.

In patients with localized prostate cancer, radical prostatectomy and radiation therapy, although effective in controlling localized disease, are often associated with significant side effects attributable to injury of adjacent tissues. Moreover, patients with metastatic disease eventually fail systemic hormonal or chemotherapy because of the development of progressive, refractory disease. In this study, we evaluated the safety and efficacy of a novel suicide gene therapy that could potentially spare normal tissue while bypassing molecular mechanisms of apoptosis resistance by using chemically inducible effector caspases to trigger apoptosis in prostate cancer cells. Initially, we compared the ability of a panel of inducible Fas signaling intermediates to kill human and murine prostate cancer cell lines. On the basis of the superior killing by downstream caspase-1 and caspase-3, replication-deficient adenoviral vectors expressing conditional caspase-1 (Ad-G/iCasp1) or caspase-3 (Ad-G/iCasp3), regulated by nontoxic, lipid-permeable, chemical inducers of dimerization (CID), were constructed. Upon vector transduction followed by CID administration, aggregation and activation of these recombinant caspases occur, leading to rapid apoptosis. In vitro, both human (LNCaP and PC-3) and murine (TRAMP-C2 and TRAMP-C2G) prostate cancer cell lines were efficiently transduced and killed in a CID-dependent fashion. In vivo, direct injection of Ad-G/iCasp1 into s.c. TRAMP-C2 tumors caused focal but extensive apoptosis without evidence for a bystander effect at the maximal viral dose (i.e., 2.5 x 10(10) viral particles/25 microl) in host animals that also received CID compared with control animals. Treatment with Ad-G/iCasp1 plus CID resulted in a transient, yet significant, reduction both in tumor growth and volume compared with tumors treated with vector but not CID (P < 0.035) or vector-diluent plus CID (P < 0.022), both of which grew more rapidly. These results demonstrate that CID-regulated, caspase-based suicide gene therapy is safe and can inhibit the growth of experimental prostate cancer in vitro and in vivo through potent induction of apoptosis, providing a rationale for further development.

Adenocarcinoma↗
PubMed2001

Comparison of MPEG-1 digital videotape with digitized sVHS videotape for quantitative echocardiographic measurements.

Digital format is rapidly emerging as a preferred method for displaying and retrieving echocardiographic studies. The qualitative diagnostic accuracy of Moving Pictures Experts Group (MPEG-1) compressed digital echocardiographic studies has been previously reported. The goals of the present study were to compare quantitative measurements derived from MPEG-1 recordings with the super-VHS (sVHS) videotape clinical standard. Six reviewers performed blinded measurements from still-frame images selected from 20 echocardiographic studies that were simultaneously acquired in sVHS and MPEG-1 formats. Measurements were obtainable in 1401 (95%) of 1486 MPEG-1 variables compared with 1356 (91%) of 1486 sVHS variables (P <.001). Excellent agreement existed between MPEG-1 and sVHS 2-dimensional linear measurements (r = 0.97; MPEG-1 = 0.95[sVHS] + 1.1 mm; P <.001; Delta = 9% +/- 10%), 2-dimensional area measurements (r = 0.89), color jet areas (r = 0.87, p <.001), and Doppler velocities (r = 0.92, p <.001). Interobserver variability was similar for both sVHS and MPEG-1 readings. Our results indicate that quantitative off-line measurements from MPEG-1 digitized echocardiographic studies are feasible and comparable to those obtained from sVHS.

Echocardiography↗
PubMed2001

Total arterial compliance is a major determinant of peak oxygen uptake.

Total arterial compliance (TAC, defined as dV/dP), is a major component of the arterial system. A decreased TAC increases left ventricular load and has a detrimental effect on coronary perfusion. We sought to assess the influence of TAC on the functional reserve (VO2max). Fourteen patients (mean age 64 +/- 14y) with known or suspected coronary artery disease and eleven controls (34 +/- 5y) underwent supine bicycle exercise echocardiography. Audio Doppler signal output of the echocardiographic machine was digitized with a customized hardware and software interface simultaneously with carotid tonometry and ECG. TAC at rest was calculated by the pulse pressure method (PPM). By step-wise forward multivariate analysis, independent predictors of VO2max were patient versus control status, peak exercise cardiac output and TAC. The described PC-based acquisition system for tonometry and Doppler signals permits the assessment of ventricular function and arterial biomechanics.

Adult↗
PubMed2000

Bcl-2 accelerates multistep prostate carcinogenesis in vivo.

The impact of bcl-2 proto-oncogene expression on the pathogenesis and progression of prostate cancer was examined in a transgenic mouse model. Probasin-bcl-2 transgenic mice were crossed with TRAMP (TRansgenic Adenocarcinoma Mouse Prostate) mice that express the SV40 early genes (T/t antigens) under probasin control. Prostate size, cell proliferation, apoptosis, and the incidence and latency of tumor formation were evaluated. The double transgenic, probasin-bcl-2 X TRAMP F1 (BxT) mice exhibited an increase in the wet weight of the prostate. This was associated with an increase in proliferation, attributable to T/t antigens, and a decrease in apoptosis attributable to bcl-2. The latency to tumor formation was also decreased in the BxT mice compared to the TRAMP mice. The incidence of metastases was identical in both the TRAMP and BxT mice. Lastly, the incidence of hormone-independent prostate cancer was reduced in the BxT mice compared to the TRAMP mice. Together, these results demonstrate that bcl-2 can facilitate multistep prostate carcinogenesis in vivo.

Adenocarcinoma↗
PubMed2000

Efficacious chemoprevention of primary prostate cancer by flutamide in an autochthonous transgenic model.

Although the etiology of prostate cancer is still not clear, family history, hormones, and age are thought to play a role in its initiation and progression. There is no cure for the advanced disease. Because prostate cancer initially develops as an androgen-dependent tumor, agents with antiandrogen activity have become the focus for chemoprevention of this disease. A pilot study was undertaken to test the efficacy of flutamide (an antiandrogen) in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of prostate cancer. Three groups of mice received s.c. implantation of slow-release flutamide pellets: (a) low-dose flutamide group (6.6 mg/kg); (b) high-dose flutamide group (33 mg/kg); and (c) control placebo group. Efficacy was measured by the absence of palpable tumor formation. Prostate tissues/tumors were harvested for evaluation by molecular and histology techniques. The low-dose flutamide group did not differ significantly from the placebo group, in which palpable tumors initially presented at 17 weeks of age, and by 33 weeks, all of the animals developed palpable tumors. In the high-dose flutamide group, however, tumors did not appear until 24 weeks, a lag of 7 weeks, and by 34 weeks, 42% of the animals were still tumor free. The period of time at which 50% of the animals had tumors was 33 weeks in the high-dose flutamide group, 24.5 weeks in the low-dose flutamide group, and 24.5 weeks in the placebo group. The difference between the placebo and high-dose flutamide groups was statistically significant (log rank, P = 0.0036; Wilcoxon's statistical analysis, P = 0.0060). Tumors from high-dose flutamide-treated animals were more differentiated and retained much of the normal glandular architecture compared with those of the placebo group, whose tumors consisted of sheets of poorly differentiated cells. The expression of T antigen in the prostate tissues of flutamide-treated animals (at 10 weeks age) was lower than that in the comparable placebo-treated group. Flutamide had the ability to suppress T antigen-driven carcinogenesis, resulting in a significant decrease in the incidence of prostate cancer and an increase in the latency period of prostate cancer in TRAMP mice.

Adenocarcinoma↗
PubMed2000

Isolation and characterization of mouse probasin: An androgen-regulated protein specifically expressed in the differentiated prostate.

BACKGROUND: The development and growth of the prostate gland is regulated, in part, by a variety of steroid and polypeptide growth-factor hormones. As a consequence of hormone action, the prostate gland will produce a number of tissue-restricted gene products. Characterization of the regulation, expression, and function of genes encoding prostate-specific proteins is critical to our understanding of prostate biology. Probasin is a prostate-specific gene originally isolated from the rat and has been exploited as a marker of prostate differentiation and to elucidate androgen action. Furthermore, a number of transgenic mouse models of prostate cancer have been established based on the regulatory elements derived from the rat probasin gene. In this report, we describe the isolation and characterization of the mouse probasin ortholog to further facilitate studies related to hormone action in the prostate and the generation and characterization of novel autochthonous models of prostate cancer. METHODS: Mouse probasin cDNA was isolated from a phage library, and the DNA sequence was determined. The predicted protein sequence was used to generate specific oligonucleotide primers and antibodies. Probasin protein and RNA expression were examined by immunobloting, immunohistochemistry, and RT-PCR, in normal mouse prostate tissue and tumor tissues derived from the autochthonous "transgenic adenocarcinoma of the mouse prostate" (TRAMP) model. Regulation of probasin expression in response to surgical castration and hormone supplementation was also characterized. RESULTS: Several points of evolutionary sequence conservation were identified between mouse and rat probasin, especially in the 3' untranslated region. Specific polyclonal antibodies were generated to peptide fragments, and the temporal and spatial pattern of probasin expression was examined. The expression of probasin was primarily localized to the apical membrane of differentiated secretory epithelium. Probasin mRNA and protein were absent from the poorly differentiated tissue of TRAMP tumors. Probasin was found to be androgen-regulated. In contrast to data from studies on rat probasin, no postcastration rebound of mouse probasin mRNA was observed. CONCLUSIONS: Probasin is a marker of differentiation and androgen action in the mouse prostate, and strong sequence conservation between mouse and rat probasin supports an essential role for this gene in the biology of the prostate gland. Isolation and characterization of mouse probasin will facilitate further development and analysis of autochthonous mouse models of prostate cancer.

Amino Acid Sequence↗