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Biomedical subjects

S Green

Publications and source records attributed to S Green.

At least 145 records · Page 8Linked to original sources
PubMed1998

The nitric oxide synthesis inhibitor L-NAME produces anxiogenic-like effects in the rat elevated plus-maze test, but not in the social interaction test.

The effects of the nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME) were investigated in two animal models of anxiety: the elevated plus-maze and the social interaction test. In the elevated plus-maze, L-NAME (12.5-50 mg/kg) had an anxiogenic-like profile as indicated by dose-dependent reductions in the time spent on the open arms, open arm entries, the percentage of open arm entries and head dips, but there was no significant effect on the number of stretch attend postures. In contrast, L-NAME (12.5-50 mg/kg) failed to modify time spent in social interaction but did reduce a measure of vertical activity. The differential effects of L-NAME in the two anxiety paradigms are discussed.

Animals↗
PubMed1998

Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study.

PURPOSE: To compare failure-free survival (FFS) and overall survival (OS) for patients with metastatic breast cancer treated with the gonadotropin-releasing hormone (GN-RH) agonist, goserelin versus surgical ovariectomy. PATIENTS AND METHODS: Between August 1, 1987 and July 15, 1995 138 (136 eligible) premenopausal patients with estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive metastatic breast cancer were entered by the Southwest Oncology Group (SWOG), North Central Cancer Treatment Group (NCCTG), and Eastern Cooperative Oncology Group (ECOG). Prior chemotherapy or hormone therapy for metastatic disease was not allowed. Patients were randomly assigned to goserelin (3.6 mg subcutaneously every 4 weeks; (n = 69) versus surgical ovariectomy (n = 67). The study was initially designed as an equivalence trial with 80% power to rule out a 50% improvement in survival due to ovariectomy. However, accrual was slow and the study was terminated early, which resulted in a final power of 60% for the alternative hypothesis of equal survival distributions. RESULTS: FFS and OS were similar for goserelin and ovariectomy. The goserelin/ovariectomy death hazards ratio was .80 and the associated 95% confidence interval (CI) was .53 to 1.20. The test of 50% improvement in survival due to ovariectomy was rejected at P = .006. Goserelin lowered serum estradiol to postmenopausal levels. Hot flashes (75% v 46%) and tumor flare (16% v 3%) were more common with goserelin. CONCLUSION: Goserelin and ovariectomy resulted in similar FFS and OS. We can rule out a moderate advantage for ovariectomy. Goserelin was safe and well tolerated.

Adult↗
PubMed1998

Molecular evolution of dengue type 2 virus in Thailand.

Dengue is a mosquito-borne viral infection that in recent years has become a major international public health concern. Dengue hemorrhagic fever (DHF), first recognized in Southeast Asia in the 1950s, is today a leading cause of childhood death in many countries. The pathogenesis of this illness is poorly understood, mainly because there are no laboratory or animal models of disease. We have studied the genetic relationships of dengue viruses of serotype 2, one of four antigenically distinct dengue virus groups, to determine if viruses obtained from cases of less severe dengue fever (DF) have distinct evolutionary origins from those obtained from DHF cases. A very large number (73) of virus samples from patients with DF or DHF in two locations in Thailand (Bangkok and Kamphaeng Phet) were compared by sequence analysis of 240 nucleotides from the envelope/nonstructural protein 1 (E/NS1) gene junction of the viral genome. Phylogenetic trees generated with these data have been shown to reflect long-term evolutionary relationships among strains. The results suggest that 1) many different virus variants may circulate simultaneously in Thailand, thus reflecting the quasispecies nature of these RNA viruses, in spite of population immunity; 2) viruses belonging to two previously distinct genotypic groups have been isolated from both DF and DHF cases, supporting the view that they arose from a common progenitor and share the potential to cause severe disease; and 3) viruses associated with the potential to cause DHF segregate into what is now one, large genotypic group and they have evolved independently in Southeast Asia for some time.

Dengue↗
PubMed1998

Hypothermia reduces neurologic deficits associated with placement of a vascular prosthesis in the abdominal aorta of rabbits.

Treatment for atherosclerotic vascular disease in human beings ranges from medical management to interventional therapy, such as angioplasty, atherectomy, and bypass grafting. Recently, bypass grafting with a vascular prosthesis has received increased attention and clinical use. In the course of studies to optimize use of a small-caliber vascular prosthesis, five of six rabbits undergoing implantation of a polytetrafluoroethylene vascular prosthesis in the infrarenal abdominal aorta developed hind limb neurologic deficits, which resulted from focal ischemic damage to the spinal cord attributable to temporary vascular occlusion of the abdominal aorta during placement of the vascular prosthesis. In subsequent studies, induction of systemic hypothermia decreased the rate of development of neurologic deficits from 83 to 9% without any apparent perioperative complications associated with decreased body temperature. We determined that mild hypothermia (rectal temperature of 32 to 35 degrees C), combined with aortic occlusion time of < 40 min, is sufficient to afford protection from ischemic injury to the spinal cord in the rabbit.

Animals↗
PubMed1998

HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: a Southwest Oncology Group Study.

HER-2/neu is a growth factor receptor, the expression of which has been associated with a more aggressive breast tumor biology and resistance to some types of chemotherapy. Preliminary laboratory and clinical data have led to claims that HER-2/neu expression is also associated with resistance to tamoxifen. Therefore, to test the hypothesis that HER-2/neu expression is associated with a poorer response to tamoxifen, a shorter time to treatment failure (TTF), and worse survival in estrogen receptor (ER)-positive metastatic breast cancer, we examined 205 paraffin-embedded blocks of tumors from patients enrolled on Southwest Oncology Group 8228 for HER-2/neu expression. Tumors were ER positive (ER level > 3 fmol/mg cytosolic protein in either primary tumors or metastases), and patients had not received any prior therapy for metastatic disease. All patients were treated with daily tamoxifen. The study began in 1982, and median follow-up of patients who are still alive is now 9 years. Membrane staining for HER-2/neu was evaluated by immunohistochemistry using antibody TAB 250 and was scored according to the proportion of cells staining positive; tumors were deemed positive if > 1% of the cells stained for HER-2/neu. HER-2/neu positivity was associated with lower ER values (P = 0.04) and low bcl-2 (P = 0.01). HER-2/neu positivity was not significantly associated with response rate (negative versus positive, 57 versus 54%; P = 0.67), TTF (median, 8 versus 6 months; P = 0.15), or survival (median, 31 versus 29 months; P = 0.36). There was also no significant evidence of a progressive relationship between an increasing proportion of cells expressing HER-2/neu and a shorter TTF or survival. HER-2/neu expression in ER-positive metastatic breast cancer is not significantly associated with a poorer response to tamoxifen or a more aggressive clinical course. Earlier suggestions to the contrary may have been due to failure to rigorously exclude ER-negative tumors, which are much less likely to respond to tamoxifen and more likely to have high HER-2/neu levels.

Adult↗
PubMed1998

Nutritional screening and assessment.

Health professionals need to take part in nutritional screening and assessment. Nutritional screening tools must meet criteria for reliability and validity. A number of assessment techniques can be used to establish nutritional status. Effective interdisciplinary working can improve outcome.

Education, Nursing, Continuing↗
PubMed1998

Heat shock proteins hsp27 and hsp70: lack of correlation with response to tamoxifen and clinical course of disease in estrogen receptor-positive metastatic breast cancer (a Southwest Oncology Group Study).

In this study, we tested the hypothesis that heat shock proteins (hsps) 27 and 70 are associated with clinical resistance to tamoxifen. hsp27 is, like progesterone receptor, an estrogen-regulated protein. hsp70 is also of interest because of its interaction with estrogen receptors and because hsp70 is a component of the molecular chaperone machinery functioning in the assembly and trafficking of steroid receptors. In addition, hsps in general help protect cells against noxious stimuli and stress, and their expression has been linked to drug resistance. The study involved 205 tumors from estrogen receptor-positive tamoxifen-treated breast cancer patients with metastatic disease. All patients received daily tamoxifen as initial therapy for metastatic disease. The study began in 1982, and follow-up is now 9 years. hsp27 and hsp70 were detected by immunohistochemistry and scored according to the nuclear and/or cytoplasmic content. Expression of hsp27 or hsp70 was unrelated to estrogen receptor content, progesterone receptor content, menopausal status, age, and presence of visceral disease. Cytoplasmic and nuclear hsp27 positivities were weakly and inversely related to each other (P = 0.05). There was a significant association between cytoplasmic hsp27 and cytoplasmic hsp70 content (P < 0.001), as well as between nuclear hsp70 and nuclear hsp27 content (P = 0.001). Cytoplasmic and nuclear hsp70 were also associated (P = 0.02). However, increased hsp27 and hsp70 expression (nuclear or cytoplasmic) was not significantly associated with response to tamoxifen, time to treatment failure, or survival. Thus, this study clarifies the lack of clinical utility of hsp27 and hsp70 in predicting the response to tamoxifen in an estrogen receptor-positive breast cancer population.

Adult↗
PubMed1998

Assessment of human CD4+ and CD8+ T lymphocyte responses in experimental viral vaccine studies.

The traditional in vitro correlate of immunological protection is the induction by a vaccine of neutralizing antibodies against the virus. It was formerly assumed that protection induced by a vaccine was solely due to neutralizing antibodies. Neutralizing antibodies are potent in the prevention of certain diseases, but virus-specific CD4+ T helper cells aid in the proliferation of specific antigen-triggered B cells to make antibodies. CD8+ T cells are responsible for eliminating virus-infected cells during viral illness, and may act as a second line of defence by becoming activated and eliminating any cells that become infected despite the presence of neutralizing antibodies, for example because of a large challenge dose or antigenic variation at the antibody combining sites. We will briefly review our approaches for measuring human virus-specific CD4+ and CD8+ T cell responses to experimental vaccines. It is critically important to have sensitive, quality controlled assays, including positive controls. There are many potential variables in human T cell assays and pitfalls, which usually result in negative CTL results. Uninterpretable data are to be expected unless adequate preliminary testing has been done to establish sensitive, specific and controlled human antigen specific CD4+ and CD8+ T cell assays.

B-Lymphocytes↗
PubMed1997

Regulation of apoptosis by BH3 domains in a cell-free system.

BACKGROUND: The Bcl-2 family of proteins plays a key role in the regulation of apoptosis. Some family members prevent apoptosis induced by a variety of stimuli, whereas others promote apoptosis. Competitive dimerisation between family members is thought to regulate their function. Homologous domains within individual proteins are necessary for interactions with other family members and for activity, although the specific mechanisms might differ between the pro-apoptotic and anti-apoptotic proteins. RESULTS: Using a cell-free system based on extracts of Xenopus eggs, we have investigated the role of the Bcl-2 homology domain 3 (BH3) from different members of the Bcl-2 family. BH3 domains from the pro-apoptotic proteins Bax and Bak, but not the BH3 domain of the anti-apoptotic protein Bcl-2, induced apoptosis in this system, as determined by the rapid activation of specific apoptotic proteases (caspases) and by DNA fragmentation. The apoptosis-inducing activity of the BH3 domains requires both membrane and cytosolic fractions of cytoplasm, involves the release of cytochrome c from mitochondria and is antagonistic to Bcl-2 function. Short peptides, corresponding to the minimal sequence of BH3 domains required to bind anti-apoptotic Bcl-2 family proteins, also trigger apoptosis in this system. CONCLUSIONS: The BH3 domains of pro-apoptotic proteins are sufficient to trigger cytochrome c release, caspase activation and apoptosis. These results support a model in which pro-apoptotic proteins, such as Bax and Bak, bind to Bcl-2 via their BH3 domains, inactivating the normal ability of Bcl-2 to suppress apoptosis. The ability of synthetic peptides to reproduce the effect of pro-apoptotic BH3 domains suggests that such peptides may provide the basis for engineering reagents to control the initiation of apoptosis.

Animals↗
PubMed1997

Recognition of dengue virus NS1-NS2a proteins by human CD4+ cytotoxic T lymphocyte clones.

We examined nine dengue virus-specific human CD4+ CD8- cytotoxic T lymphocyte (CTL) clones for protein recognition, using recombinant vaccinia viruses which contain genes coding for dengue virus proteins. These clones were established from peripheral blood mononuclear cells of a donor previously immunized with a live-attenuated experimental dengue-1 vaccine. Of nine CD4+ T cell clones, seven were dengue-1-specific and two were dengue-1-dengue-3 cross-reactive. Four dengue-1-specific clones and one dengue-1-dengue-3 cross-reactive clone recognized epitopes within the NS1 or NS2a proteins. Analysis of human leukocyte antigen (HLA) restriction revealed that three dengue-1-specific clones are HLA-DR1-restricted and one dengue-1-dengue-3 cross-reactive clone is HLA-DPw3-restricted. These results indicate that NS1 and NS2a proteins as well as C, E, and NS3 proteins reported earlier contain one or more epitopes recognized by dengue virus-specific human CD4+ T lymphocytes.

Antigens, Viral↗
PubMed1997

Practical application of non-whole animal alternatives: summary of IRAG workshop on eye irritation testing. Interagency Regulatory Alternatives Group.

In November 1993, the Interagency Regulatory Alternatives Group (IRAG) sponsored a workshop to examine the current scientific status of alternatives to the Draize eye irritation test by assessing the current practical application of methods used to predict in vivo eye irritation. Laboratories from around the world were invited to submit detailed in vitro and in vivo data in parallel according to a specific set of guidelines in a consistent format. In vitro scores were compared with individual tissue scores. Over 60 data sets from 41 laboratories were received for 29 different test methods. Methods were grouped into five categories: organotypic models, chorioallantoic membrane-based assays, cell function-based assays, cytotoxicity assays and other systems. Data submissions and correlation analyses have been used to demonstrate the application of guidelines in method evaluations. Findings are summarized and future directions are indicated. A significant outcome of the workshop was the co-operation demonstrated among representatives of industry, academia and government in sharing test data on more than 2000 chemicals, products and product formulations for evaluation by their peers. Information obtained from this workshop will add to the weight of scientific evidence and scientific consensus about in vitro test methods and will establish credibility for regulatory acceptance of non-whole animal alternatives for ocular irritation.

Animal Testing Alternatives↗
PubMed1997

Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions.

A total of 167 human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis were randomly assigned to receive 14 days of therapy with liquid suspension fluconazole (100 mg once daily) or liquid nystatin (500,000 U four times daily). At day 14, 87% of the fluconazole-treated patients were clinically cured, as opposed to 52% in the nystatin-treated group (P < .001). Fluconazole eradicated Candida organisms from the oral flora in 60%, vs. a 6% eradication rate with nystatin (P < .001). The fluconazole group had fewer relapses noted on day 28 (18%, vs. 44% in the nystatin group; P < .001). This relapse difference no longer existed by day 42. Fluconazole oral suspension as a systemic therapy was more effective than liquid nystatin as a topical therapy in the treatment of oral candidiasis in HIV-infected patients and provided a longer disease-free interval before relapse.

AIDS-Related Opportunistic Infections↗
PubMed1997

Early clinical and laboratory indicators of acute dengue illness.

A prospective observational study was conducted to identify early indicators of acute dengue virus infection. Children with fever for <72 h without obvious cause were studied at hospitals in Bangkok and Kamphaeng Phet, Thailand, until resolution of fever. Of 172 evaluable subjects (91% of enrollees), 60 (35%) had dengue, including 32 with dengue fever (DF) and 28 with dengue hemorrhagic fever (DHF). At enrollment, children with dengue were more likely than children with other febrile illnesses (OFI) to report anorexia, nausea, and vomiting and to have a positive tourniquet test, and they had lower total white blood cell counts, absolute neutrophil and absolute monocyte counts, and higher plasma alanine and aspartate (AST) aminotransferase levels than children with OFI. Plasma AST levels were higher in children who developed DHF than in those with DF. These data identify simple clinical and laboratory parameters that help to identify children with DF or DHF.

Acute Disease↗
PubMed1997

Dengue in the early febrile phase: viremia and antibody responses.

A multicenter effort was begun in 1994 to characterize the pathophysiology of dengue using a study design that minimized patient selection bias by offering enrollment to all children with undifferentiated fever for <72 h. In the first year, 189 children were enrolled (age range, 8 months to 14 years). Thirty-two percent of these children had dengue infections (60 volunteers). The percentage of children with a secondary dengue infection was 93%, with only 4 (7%) having a primary dengue infection. The virus isolation rate from the plasma of children with dengue was 98%. Viremia correlated highly with temperature. All four dengue virus serotypes were isolated at both study sites. This study demonstrates that all four serotypes of dengue virus can cause dengue hemorrhagic fever, that all dengue patients as defined by serology experience viremia during the febrile phase, and that as fever subsides, so does viremia.

Acute Disease↗
PubMed1997

The response of a MOSFET, p-type semiconductor and LiF TLD to quasi-monoenergetic x-rays.

A metal oxide semiconductor field effect transistor (MOSFET), p-type semiconductor and a TLD can all be used for x-ray dosimetry, with each system having the common disadvantage of a response which is dependent upon the incident photon energy, particularly for energies < 1 MeV. A Pantak HF-320 quasi-monoenergetic x-ray unit was used to determine the response of two Thomson and Nielson TN-502RD MOSFETs, a Scanditronix EDP-10 semiconductor (build-up cap 10 mm: tissue equivalence), an EDD-5 semiconductor (build-up cap 4.5 mm: tissue equivalence) and an Lif:Mg:Ti TLD over the energy range 12-208 keV. The sensitivity of each detector was normalized to the value produced by exposure to 6 MV x-rays. The maximum relative sensitivities of the two MOSFET detectors were 4.19 +/- 0.25 and 4.44 +/- 0.26 respectively, occurring at an incident x-ray energy of 33 keV. The maximum relative sensitivity of the Scanditronix EDP-10 of 2.24 +/- 0.13 occurred at 65 keV, and for the EDD-5, it was 7.72 +/- 0.45 at 48 keV. The TLD produced a maximum relative sensitivity of 1.31 +/- 0.09 at 33 keV. Compared with available data based on heteroenergetic x-ray sources, these measurements have identified a more representative response for each detector to low-energy x-rays.

Equipment Design↗
PubMed1997

The 40K activity of one gram of potassium.

The activity of 40K in natural potassium as derived from the recent literature varies between 27.33 to 31.31 Bq g-1 of potassium. This paper reports measurements by gamma-ray spectrometry and compares these with independent calculations, yielding values of 30.18 +/- 0.72 Bq g-1 and 31.00 +/- 0.33 Bq g-1 respectively.

Gamma Rays↗