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Biomedical subjects

G Simmons

Publications and source records attributed to G Simmons.

At least 55 records · Page 3Linked to original sources
PubMed1997

The effect of intravenous ketorolac given intraoperatively versus postoperatively on outcome from gynecologic abdominal surgery.

STUDY OBJECTIVES: To examine the effect of timing of an intravenous (i.v.) dose (intraoperative vs. postoperative) of ketorolac tromethamine on pain scores and overall outcome after total abdominal hysterectomy (TAH) and myomectomy. DESIGN: Prospective, randomized, placebo-controlled study. PATIENTS: 248 ASA physical status I and II adult female patients scheduled for elective hysterectomy or myomectomy. INTERVENTIONS: General anesthesia was administered that consisted of thiopental sodium for induction, enflurane or isoflurane in nitrous oxide-oxygen for maintenance, and small doses of fentanyl and midazolam. Patients were randomized into three groups to receive toradol/placebo on a dosing schedule of dose 1 given one-half hour prior to expected end of surgery, dose 2 given on awakening in the postanesthesia care unit, and doses 3, 4, and 5 given at 6, 12, and 18 hours, respectively, after dose 2; Group 1 patients received placebo (saline) for dose 1, ketorolac 60 mg i.v. for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 2 patients received ketorolac 60 mg i.v. for dose 1, placebo for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 3 patients received placebo for all doses. All patients were given i.v. morphine PCA postoperatively, and morphine usages, visual analog pain intensity (VAS) scores, as well as adverse events and median times to recovery milestones were recorded. MEASUREMENTS AND MAIN RESULTS: VAS scores (mean) before dose 2 were significantly lower in Group 2 than Group 1, as were at-rest evaluations at 15 minutes and one hour. Group 2 patients also had decreased morphine requirements as compared to placebo. Both ketorolac groups (Groups 1 and 2) had significantly higher values for patient and observer overall ratings, case of nursing care, and tolerability as compared to placebo (Group 3). There were no significant differences among groups in adverse events or median times to recovery milestones. CONCLUSIONS: Although it is possible to demonstrate an improvement in early postoperative pain scores with intraoperative ketorolac and better overall ratings of ketorolac both intraoperatively and postoperatively as compared with placebo, the lack of clinically significant differences in analgesic efficacy in the two active study groups indicates the need for a careful consideration by the clinician of the risks versus benefits involved in the administration of antiplatelet medication in the perioperative period.

Adult↗
PubMed1997

Langerhans cell tropism of human immunodeficiency virus type 1 subtype A through F isolates derived from different transmission groups.

To test the hypothesis that some subtypes of human immunodeficiency virus type 1 (HIV-1), especially subtype E, are more likely to infect mature Langerhans cells (mLC), we titrated a panel of 26 primary HIV-1 isolates of subtypes A through F on peripheral blood mononuclear cells (PBMC) and mLC. The majority of HIV-1 isolates from heterosexually infected patients did not show a preferred tropism for mLC compared to homosexually transmitted HIV-1 isolates. Only 6 of 26 isolates, 2 from patients infected by homosexual contact and 4 from patients infected by heterosexual contact, showed a higher infectivity for mLC than for PBMC. Both syncytium-inducing and non-syncytium-inducing isolates were able to infect mLC which express mRNA for the chemokine receptors CCR3, CCR5, and CXCR4.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Inhibition of human immunodeficiency virus fusion by a monoclonal antibody to a coreceptor (CXCR4) is both cell type and virus strain dependent.

CXCR4 (also termed fusin, LESTR, or HUMSTR) is a member of the G-protein-coupled chemokine receptor family with seven membrane-spanning domains. CXCR4 acts as a coreceptor for syncytium-inducing human immunodeficiency virus type 1 (HIV-1) strains, conferring entry into CD4+ cells. We show here that a novel mouse monoclonal antibody (12G5) that recognizes CXCR4 blocked cell-to-cell fusion and cell free-virus infection of CXCR4+ CD4+ RD rhabdomyosarcoma cells by seven HIV-1 and HIV-2 strains that had various cell tropisms for different CD4+ human cell types. Yet the majority of the members of the same virus panel resisted 12G5 inhibition on T-cell lines. When inhibition was observed on these cell types, it was both cell type and virus strain dependent. In at least one situation, 12G5 failed to block LAI infection of cells expressing CXCR4 as the only available coreceptor. Our observations suggest that CXCR4 could be processed or presented differently depending on the cell type, allowing some strains to evade 12G5 inhibition. Alternatively, since several of the viruses could infect certain CXCR4- CD4+ cell lines, it is conceivable that alternative coreceptors are active, enabling individual HIV strains to choose between compatible coreceptors during entry into cells. Moreover, the strain dependency of 12G5 inhibition implies that the interaction of different HIVs with CXCR4 varies.

Animals↗
PubMed1997

Multiple extracellular domains of CCR-5 contribute to human immunodeficiency virus type 1 entry and fusion.

Human immunodeficiency virus type 1 (HIV-1) entry is governed by the interaction of the viral envelope glycoprotein (Env) with its receptor. The HIV-1 receptor is composed of two molecules, the CD4 binding receptor and a coreceptor. The seven-membrane-spanning chemokine receptor CCR-5 is one of the coreceptors used by primary isolates of HIV-1. We demonstrate that the mouse homolog of CCR-5 (mCCR-5) does not function as an HIV-1 coreceptor. A set of chimeras of human CCR-5 and mCCR-5 was studied for Env-induced cell fusion and HIV-1 infection. Using the HIV-1ADA envelope glycoprotein in a syncytium formation assay, we show that replacement of any fragment containing extracellular domains of mCCR-5 by its human counterparts is sufficient to allow Env-induced fusion. Conversely, replacement of any fragment containing human extracellular domains by its murine counterpart did not lead to coreceptor function loss. These results show that several domains of CCR-5 participate in coreceptor function. In addition, using a panel of primary nonsyncytium-inducing and syncytium-inducing isolates that use CCR-5 or both CXCR-4 and CCR-5 as coreceptors, we show that the latter dual-tropic isolates are less tolerant to changes in CCR-5 than strains with a more restricted coreceptor use. Thus, different strains are likely to have different ways of interacting with the CCR-5 coreceptor.

Amino Acid Sequence↗
PubMed1997

Biological characterization of human immunodeficiency virus type 1 clones derived from different organs of an AIDS patient by long-range PCR.

In order to characterize the biological properties of human immunodeficiency virus type 1 (HIV-1) variants from different tissues (peripheral blood mononuclear cells [PBMC], lymph node, spleen, brain, and lung) of one patient, we have chosen long-range PCR to amplify virtually full-length HIV proviruses and to construct replication-competent viruses by adding a patient-specific 5' long terminal repeat. To avoid selection during propagation in CD4+ target cells, we transfected 293 cells and used the supernatants from these cells as challenge viruses for tropism studies after titration on human PBMC. Despite differences in the V3 loop of the major variants found in brain and lung compared to lymphoid tissues all recombinant HIV clones obtained showed identical cell tropism and replicative kinetics. After infection of human PBMC these viruses replicated with similar kinetics, with a slow/low-titer, non-syncytium-inducing phenotype. In contrast to the prediction of macrophage tropism, drawn from the V3 loop sequence, none of these viruses infected monocyte-derived macrophages. The challenge of blood dendritic cells by these recombinant viruses in the presence of tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and interleukin-4 resulted in a productive infection only after adding stimulated CD4+ T lymphocytes. Therefore, the biological properties of the HIV-1 variants derived from nonlymphoid tissue of this patient did not differ from those of HIV-1 variants from lymphoid tissue with respect to tropism for primary cells such as PBMC, macrophages, and blood dendritic cells.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The increasing prevalence of obesity in New Zealand: is it related to recent trends in smoking and physical activity?

AIMS: To describe recent trends in body mass in Auckland, and to determine whether associated changes in cigarette smoking and physical activity could explain these trends. METHODS: Risk factors for coronary heart disease were measured in three age-stratified random samples of Europeans aged 35-64 years using a standard protocol in 1982, 1986-8 and 1993-4. Body mass index (BMI) was calculated as weight in kg/(height in m2), with overweight or obese being defined as BMI>25. Results. The age-standardised mean BMI increased from 26.6 (25.4-25.8) to 26.4 (26.2-26.7) in men and from 24.6 (24.2-24.9) to 25.1 (24.8-25.5) in women between 1982 and 1993-4. The prevalence of overweight and obese people increased from 52.8% (48.1-57.7) to 64.2% (58.1-70.3) in men and from 36.5% (31.5-41.5) to 44.9% (39.7-50.1) in women. Self reported cigarette smoking declined between 1982 and 1993-94 with an associated increase in the prevalence of ex-smokers. The change in smoking status accounted for only 7% and 10% of the observed increase in BMI in men and women respectively. Most of the observed change in BMI was due to a general increase in BMI in all smoking categories in both sexes. The prevalence o leisure time physical activity increased in both sexes between 1986-88 and 1993-94 while work physical activity decreased. The change in physical activity should have decreased mean BMI by approximately 4% in men and 14% in women. As with smoking there was a trend towards increasing mean BMI irrespective of the activity undertaken. CONCLUSION: Recent trends in smoking cessation explain only a small percentage of the increase in body mass while the trends in physical activity would have predicted a small decrease in the prevalence of obesity, contrary to the observed trends. By exclusion, an increase in total energy intake, is the most likely explanation for the observed trends.

Adult↗
PubMed1996

Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry.

A panel of primary syncytium-inducing (SI) human immunodeficiency virus type 1 isolates that infected several CD4+ T-cell lines, including MT-2 and C8166, were tested for infection of blood-derived macrophages. Infectivity titers for C8166 cells and macrophages demonstrated that primary SI strains infected macrophages much more efficiently than T-cell line-adapted HIV-1 strains such as LAI and RF. These primary SI strains were therefore dual-tropic. Nine biological clones of two SI strains, prepared by limiting dilution, had macrophage/C8166 infectivity ratios similar to those of their parental viruses, indicating that the dual-tropic phenotype was not due to a mixture of non-SI/macrophage-tropic and SI/T-cell tropic viruses. We tested whether the primary SI strains used either Lestr (fusin) or CCR5 as coreceptors. Infection of cat CCC/CD4 cells transiently expressing Lestr supported infection by T-cell line-adapted strains including LAI, whereas CCC/CD4 cells expressing CCR5 were sensitive to primary non-SI strains as well as to the molecularly cloned strains SF-162 and JR-CSF. Several primary SI strains, as well as the molecularly cloned dual-tropic viruses 89.6 and GUN-1, infected both Lestr+ and CCR5+ CCC/CD4 cells. Thus, these viruses can choose between Lestr and CCR5 for entry into cells. Interestingly, some dual-tropic primary SI strains that infected Lestr+ cells failed to infect CCR5+ cells, suggesting that these viruses may use an alternative coreceptor for infection of macrophages. Alternatively, CCR5 may be processed or presented differently on cat cells so that entry of some primary SI strains but not others is affected.

CD4-Positive T-Lymphocytes↗
PubMed1996

Location, exposure, and conservation of neutralizing and nonneutralizing epitopes on human immunodeficiency virus type 2 SU glycoprotein.

Eleven rat monoclonal antibodies (MAbs) that recognize the SU glycoprotein of human immunodeficiency virus type 2 (HIV-2) ROD were produced and characterized. Binding sites for eight of these MAbs were mapped to epitopes within the Cl, V1/V2, C2, and V3 envelope regions. The three other MAbs defined at least two conformation-dependent, strain-specific epitopes outside Vl/V2, V3, and the CD4-binding site. The MAbs were used to probe the tertiary structure of oligomeric envelope glycoprotein expressed on the surfaces of infected cells. Epitopes at the apices of V2 and V3 were exposed on the native molecule, whereas other epitopes on V1/V2, Cl, and C2 were hidden. The MAbs defined three neutralization targets on exposed domains: two linear epitopes in the V2 and the V3 loops and one conformational epitope outside V1, V2, and V3.

Amino Acid Sequence↗
PubMed1995

Cell-to-cell fusion, but not virus entry in macrophages by T-cell line tropic HIV-1 strains: a V3 loop-determined restriction.

T-cell lines chronically infected with laboratory adapted, T-cell tropic HIV-1 strains (RF, LAI, CBL-4, and NY5) induced syncytia after cocultivation with primary macrophages. Such fusion-competent strains, however, replicated inefficiently after cell-free infection of macrophage cultures. Evidence based on proviral DNA synthesis, pseudotype penetration, and a V3 loop mutation revealed that cell-free infection was restricted at a prepenetration stage in entry and controlled by envelope sequences. Our results suggest that primary macrophages are sensitive to cell-to-cell but not to virion-to-cell fusion induced by the envelope glycoproteins of several T-cell tropic HIV-1 strains.

Cell Communication↗
PubMed1994

Comparison of placement of the laryngeal mask airway with endotracheal tube by paramedics and respiratory therapists.

STUDY OBJECTIVE: To determine the learning curve of nonphysician emergency personnel on placement of the laryngeal mask airway as compared to performance of endotracheal intubation. DESIGN: Prospective, comparative, randomized, patient-blinded trial. SETTING: Regional hospital operating room. PARTICIPANTS: Seven experienced paramedics and 12 respiratory therapists trained in endotracheal intubation. INTERVENTIONS: Patients used as subjects were anesthetized and paralyzed. Each participant then performed placement of both the laryngeal mask airway and endotracheal tube on the same patient in random sequence. Both techniques were observed for speed, difficulty, and effectiveness. MEASUREMENTS AND MAIN RESULTS: The techniques were timed from the point at which the participant touched the patient to the time they were able to effectively ventilate the patient. Participants also were asked to rate the difficulty of each technique on a 100-mm visual analog score. Failure (three attempts without successful ventilation) rates also were monitored. The mean time to ventilate successfully with the laryngeal mask airway was significantly less than that with the endotracheal tube (38.9 +/- 1.9 seconds versus 206.1 +/- 31.9 seconds, P < .0001). The average number of attempts was 1.0 +/- 0.0 for the laryngeal mask airway and 2.22 +/- 0.21 for the endotracheal tube (P < .01). No one failed to place the laryngeal mask airway; and ten of 19 (52.6%, P < .01) failed to perform endotracheal intubation. The endotracheal tube had a significantly higher rating of difficulty than did the laryngeal mask airway (67.3 versus 8.64, P < .0001).

Allied Health Personnel↗
PubMed1993

Is CD4 sufficient for HIV entry? Cell surface molecules involved in HIV infection.

HIV-1, HIV-2 and SIV each bind to CD4 as the first step in virus entry. However, alternative receptors may also be used. HIV-1 binds to glycolipids with terminal galactosylceramide residues on neural cells; opsonized virus binds to Fc receptors; HIV-2 can infect certain CD4-negative cells. Further receptors may also play a role in CD4-mediated infection, including cell adhesion molecules and possibly cell surface proteinases. After binding to CD4, immunodeficiency viruses require secondary molecules to effect fusion between the virus envelope and the cell membrane; these accessory requirements differ between HIV-1, HIV-2 and SIV.

Animals↗
PubMed1993

[123I]HIPDM pulmonary imaging demonstrates elastase-induced pulmonary emphysema.

Because more than 90 percent of [123I]hydroxyiodobenzyl-propanediamine (HIPDM) is localized in the lung after intravenous injection, the radiopharmaceutical has been proposed as a lung imaging agent. Its potential usefulness for the detection of pulmonary emphysema was evaluated in an animal model of elastase-induced emphysema along with [99mTc]MAA lung perfusion imaging. To induce lung emphysema, Long-Evans rats (200-250 g) were given 400 IU/Kg elastase intratracheally under ether anesthesia. Four weeks after elastase treatment, 15 treated and 15 nontreated rats were paired and simultaneously imaged under a scintillation camera immediately following intravenous injection of 0.25-0.3 mCi[99mTc]MAA. The procedure was repeated 48 hr later using 0.25-0.3 mCi[123I]HIPDM. Activity in the region of interest (ROI) over the lungs was recorded after the injections. Total counts per ROI from each rat were measured and normalized by lung volume. The normalized lung activity ratio of treated/nontreated rats was computed. The mean ratios of HIPDM and MAA were 0.847 and 0.802, respectively. The significant decrease in uptake of both HIPDM (p < 0.021) and of MAA (p < 0.025) in the elastase-treated lungs indicates decrease in functioning vascular endothelium and decrease in number of pulmonary capillary vessels, respectively, reflecting damage in capillaries and small arterioles. The decrease in treated/nontreated ratios lung is consistent with a significant alteration in pulmonary function and a significant increase in mean linear intercept (p < 0.005) in treated lung. Since the imaging reflects pulmonary endothelial receptor function, [123I]HIPDM lung imaging may serve as an alternative diagnostic modality for pulmonary emphysema.

Animals↗
PubMed1991

The institutionalization of operations research.

When the conceptualization of OR is inappropriate, institutionalization will not take place. For this reason, the discussion here has focused as much on the pitfalls in OR design as on factors that facilitate institutionalization. Research that is inappropriately adapted to the societal or programmatic context will not be institutionalized, nor will OR lead to institutionalized research capabilities if theory is ignored or the research lacks credibility. The institutionalization of credible and scientifically sound OR requires well-trained social scientists who can carry out this task. Career opportunities must persist in OR so that well-trained scientists will find in an attractive and rewarding pursuit. Long-term projects facilitate institutionalization by providing a setting where work teams can be developed and career tracks defined. Academics and universities institutionalize OR by sponsoring training in applied research and developing high-level research leadership. For this reason, institutional linkages and mechanisms that nurture collaboration facilitate the institutionalization of OR. Finally, institutionalization of OR implies that research is being utilized for action by program management and the policy community. There is extensive literature on the determinants of research utilization, much of which is relevant to the question of how OR can be institutionalized.

Academies and Institutes↗
PubMed1990

I-123 hydroxyiodobenzyl propanediamine (HIPDM) cerebral blood flow imaging demonstrating transtentorial diaschisis.

To assess the clinical significance of transtentorial diaschisis (TTD) as demonstrated by I-123 HIPDM brain imaging, SPECT and/or planar images of 35 patients with stroke, 26 patients with Alzheimer's disease (AD), 2 patients with Creutzfeldt-Jakob disease (CJD), and 1 patient with a schizoaffective disorder were analyzed. TTD was observed in 21 of the 35 patients with strokes. In 13 stroke patients, TTD was associated with large infarcts in the middle cerebral artery (MCA) territory; in the remaining 8 stroke patients, TTD was associated with internal capsule and/or basal ganglia infarcts. TTD was not associated with small occipital or parietal infarcts. Despite cortical perfusion decrements, TTD was not seen in the AD patients, the CJD patients, or the patient with schizoaffective disorder. It is concluded that 1) TTD frequently occurs following cerebral infarct of the MCA territory (60% of the patients in this sample); 2) absence of TTD in the presence of a large cerebral perfusion abnormality may represent neuronal dysfunction of the cerebral cortex; and 3) the presence of TTD without a significant cortical perfusion abnormality may indicate basal ganglia and/or internal capsule infarct.

Alzheimer Disease↗
PubMed1986

Thrombin-like enzyme from the venom of Bitis gabonica. Purification, properties, and coagulant actions.

Gabonase, an enzyme which acts on fibrinogen and factor XIII in uniquely thrombin-like ways, was purified to electrophoretic homogeneity from the venom of Bitis gabonica. On sodium dodecyl sulfate-polyacrylamide electrophoresis, the reduced protein behaved as a single chain with Mr = 30,600. The enzyme contains 20.6% carbohydrate, no free sulfhydryl groups and hence, from amino acid analysis, five disulfide bonds. Its extinction coefficient (E1%1cm) at 280 nm is 9.6. Its pI is 5.3. Gabonase has an active serine residue, is inactivated by phenylmethanesulfonyl fluoride, and has an active histidine which reacts with the chloromethyl ketone of tosyl-L-lysine. Its NH2-terminal amino acid sequence (Val-Val-Gly-Gly-Ala-Glu-Cys-Lys-Ile-Asp-Gly-His-Arg-Cys-Leu-Ala-Leu-Leu -Tyr-) is homologous to the B chain of thrombin. The activity of the enzyme is stabilized by calcium ion. It exhibits strong N alpha-p-tosyl-L-arginine methyl esterase activity, hydrolyzes tripeptide nitroanilide derivatives weakly or not at all, and cleaves no peptide bonds in insulin, glucagon, or the S peptide of ribonuclease. Gabonase clots fibrinogen with a specific activity of 45 NIH thrombin-equivalent units/mg, releasing both fibrinopeptides A and B and showing substrate inhibition at fibrinogen concentrations of 3 mg/ml or greater. The enzyme also activates factor XIII. It is not inactivated by either heparin or hirudin.

Amino Acid Sequence↗
PubMed1985

Action of crotalase, an enzyme with thrombin-like and kallikrein-like specificities, on tripeptide nitroanilide derivatives.

Since crotalase has thrombin-like and kallikrein-like functional and structural properties, we compared the actions of crotalase, thrombin and plasma kallikrein on 13 tripeptide nitroanilide substrates. Initial rates of hydrolysis were determined at 27 degrees C, pH 8.3, and used to construct Lineweaver-Burk plots from which Km and Vmax were determined. The ratio of kcat/Km was taken as a measure of enzymatic specificity. Crotalase yielded kcat/Km values for the following nitroanilide substrates in descending order of magnitude: H-D-NLeu-CHA-Arg, H-D-Pro-HHT-Arg, Tos-Gly-Pro-Arg, H-D-PhGly-Phe-Arg, Cbo-Glu(BuO)-Gly-Arg, H-D-But-CHA-Lys, H-D-CHG-But-Arg, H-D-NLeu-HHT-Lys, H-D-HHT-Ala-Arg, Bz-Pro-Phe-Arg, Tos-Gly-Pro-Lys, MeS-Leu-Gly-Arg, MeO-CO-CHG-Gly-Arg. This pattern of specificity correlated only roughly with those of thrombin and kallikrein.

Chromogenic Compounds↗