Biomedical subjects

J L Johnson

Publications and source records attributed to J L Johnson.

At least 145 records · Page 8Linked to original sources

PubMed1999

Measurement of sputum Mycobacterium tuberculosis messenger RNA as a surrogate for response to chemotherapy.

Effective treatment regimens for pulmonary tuberculosis are difficult to assess because of the slow growth rate of Mycobacterium tuberculosis in culture and its protracted clearance from sputum. A rapid method that reflects effective antimicrobial activity would markedly advance evaluation of treatment and promote the assessment of new antituberculosis drugs. Conventional methods measure the progressive reduction of numbers of acid-fast bacilli in the sputum smear and the clearance of organisms in sputum culture. In this study, we measured levels of M. tuberculosis 85B (alpha antigen) messenger RNA (mRNA), 16S ribosomal RNA (rRNA), and IS6110 DNA in patients' sputa to ascertain whether they could serve as potential surrogate markers of response to chemotherapy. Sputum specimens were sequentially collected for up to a year from 19 smear-positive pulmonary tuberculosis patients receiving an optimal drug treatment regimen. Nucleic acids were isolated from these specimens, and two M. tuberculosis molecular targets (mRNA, DNA) were quantified, using the ABI Prism 7700 Sequence Detection System. The Mycobacterium genus-specific 16S rRNA was quantified with a limiting dilution RT-PCR assay. Results show that levels of 85B mRNA declined after initiation of therapy, as did viable M. tuberculosis colony counts, with 90% of patients becoming negative for both markers after 2 mo of treatment. The rapid disappearance of M. tuberculosis mRNA from sputum suggests that it is a good indicator of microbial viability and a useful marker for rapid assessment of response to chemotherapy.

Adult↗

PubMed1999

Children of substance abusers: overview of research findings.

A relationship between parental substance abuse and subsequent alcohol problems in their children has been documented extensively. Children of alcoholics (COAs) are considered to be at high risk because there is a greater likelihood that they will develop alcoholism compared with a randomly selected child from the same community. COAs and children of other drug-abusing parents are especially vulnerable to the risk for maladaptive behavior because they have combinations of many risk factors present in their lives. The single most potent risk factor is their parent's substance-abusing behavior. This single risk factor can place children of substance abusers at biologic, psychologic, and environmental risk. Since the turn of the century, many reports have described the deleterious influence of parental alcoholism on their children. A series of studies measured mortality, physiology, and general health in the offspring of alcoholic parents and concluded that when mothers stopped drinking during gestation, their children were healthier. Today, research on COAs can be classified into studies of fetal alcohol syndrome, the transmission of alcoholism, psychobiologic markers of vulnerability, and psychosocial characteristics. Each of these studies hypothesizes that differences between COAs and children of nonalcoholics influence maladaptive behaviors later in life, such as academic failure or alcoholism. This research supports the belief that COAs are at risk for a variety of problems that may include behavioral, psychologic, cognitive, or neuropsychologic deficits. The vast literature on COAs far outweighs the literature on children of other drug abusers. Relatively little is known about children of heroin addicts, cocaine abusers, or polydrug abusers. Nonetheless, many researchers suggest that the children of addicted parents are at greater risk for later dysfunctional behaviors and that they, too, deserve significant attention to prevent intergenerational transmission of drug abuse. Most research on children of other drug abusers examines fetal exposure to maternal drug abuse. The overview of the research on children of substance abusers points toward the need for better, longitudinal research in this area. Most studies on COAs or other drug abusers are not longitudinal; they examine behavior at one point in time. Given the studies reviewed in this article, it is unclear whether we see true deficits or developmental delay. Longitudinal studies will allow us to predict when early disorders and behavioral deviations will be transient or when they will be precursors to more severe types of maladaptive behavior. Longitudinal research also will enable us to explain specific childhood outcomes. Differences in outcome could be studied simultaneously to understand whether antecedents discovered for one are specific to it or are general antecedents leading to a broad variety of outcomes.

Adaptation, Psychological↗

PubMed1999

Neutrophils are primed for cytotoxicity and resist apoptosis in injured patients at risk for multiple organ failure.

BACKGROUND: Postinjury multiple organ failure (MOF) is the result of a dysregulated systemic inflammatory response in which primed neutrophils (PMNs) are sequestered in tissues, vulnerable to activation through secondary insults. Apoptosis is critical to the normal clearance of these sequestered PMNs. Conversely, dysfunctional apoptosis prolongs the PMN functional life span, potentially exacerbating PMN-mediated tissue injury and the development of MOF. We hypothesized that severe trauma, in addition to priming PMNs, provokes dysfunctional PMN apoptosis. METHODS: Neutrophils were harvested daily from 12 severely injured patients at high risk for MOF, cultured for 24 hours, and assessed for apoptosis with use of acridine orange-ethidium bromide staining and fluorescence microscopy. Priming for elastase release was measured in freshly isolated patient PMNs. Plasma from patients was assessed for its ability to delay apoptosis of normal PMNs. RESULTS: Four patients (33%) had MOF. Neutrophil apoptosis was profoundly delayed in severely injured patients throughout the 5-day study period. Priming for elastase release was augmented concomitantly. Patients' plasma delayed apoptosis of normal PMNs. CONCLUSION: In patients at high risk for postinjury MOF, PMNs are not only primed for cytotoxicity but also resist apoptosis. The dysfunctional apoptosis is attributed, at least in part, to a plasma-borne mediator. The net effect may facilitate hyperinflammatory organ injury.

Adolescent↗

PubMed1999

The effect of bacille Calmette-Guérin vaccination at birth on tuberculin skin test reactivity in Ugandan children.

SETTING: In Uganda, bacille-Calmette Guerin (BCG) vaccination coverage at birth is between 82 and 84%. OBJECTIVE: To evaluate the effect of neonatal BCG vaccination on tuberculin skin test positivity in Ugandan children exposed to infectious cases. DESIGN: As part of an ongoing prevalence study of household contacts of new tuberculosis cases, 365 children were evaluated to determine if BCG vaccination at birth had an impact on tuberculin skin testing. The children were classified as contacts (179) and non-contacts (186) depending on the presence of a sputum acid-fast bacilli (AFB) smear-positive adult tuberculosis case in the household. RESULTS: Regardless of prior BCG vaccination, children exposed to a smear-positive adult were more likely to have a positive skin test (purified protein derivative >5mm) (68% versus 36%, P < 0.01). BCG-vaccinated children below 1 year of age without a known household contact with active tuberculosis had a lower frequency of tuberculin skin reactions (29%) compared to their counterparts in the contact households (65%, P = 0.031). CONCLUSION: BCG vaccination at birth had no important effect on the interpretation of the tuberculin skin test reactivity in this group of Ugandan children. The tuberculin skin test remains a valuable tool for the evaluation of household contacts and suspected cases of tuberculosis in BCG-vaccinated children.

Adolescent↗

PubMed1999

Breast health practices and South Asian women.

Breast cancer is an important women's health issue in all communities. To detect breast cancer early, all women should practise monthly breast self-examination, have regular clinical breast examinations and attend mammography screening at suggested intervals. Participation in these breast health practices is influenced by a wide variety of factors, including how women define health and health practices, priorities in women's lives and their explanations of the causes of diseases such as cancer.

Adult↗

PubMed1998

Activation of p47(PHOX), a cytosolic subunit of the leukocyte NADPH oxidase. Phosphorylation of ser-359 or ser-370 precedes phosphorylation at other sites and is required for activity.

The leukocyte NADPH oxidase catalyzes the reduction of oxygen to superoxide (O-2) at the expense of NADPH in phagocytes and B lymphocytes. The enzyme is dormant in resting cells but becomes active when the cells are exposed to appropriate stimuli. During oxidase activation, the highly basic cytosolic oxidase component p47(PHOX) becomes phosphorylated on several serines and migrates to the plasma membrane. We report here that p47(PHOX)-deficient B lymphoblasts expressing the p47(PHOX) S359A/S370A or p47(PHOX) S359K/S370K double mutation show dramatically reduced levels of enzyme activity and phosphorylation of p47(PHOX) as compared with the same cells expressing wild type p47(PHOX). In addition, these mutant p47(PHOX) proteins fails to translocate to the plasma membrane when the cells are stimulated. In contrast, normal phosphorylation and translocation are seen in mutants containing aspartate or glutamate at positions 359 and 370, but oxidase activity is still greatly reduced. These results imply that a negative charge at position 359 and/or 370 is sufficient to allow the phosphorylation and translocation of p47(PHOX) to take place but that features unique to a phosphorylated hydroxyamino acid are required to support O-2 production. These findings, plus those from an earlier study (Inanami, O., Johnson, J. L., McAdara, J. K., El Benna, J., Faust, L. P., Newburger, P. E., and Babior, B. M. (1998) J. Biol. Chem. 273, 9539-9543), suggest that oxidase activation requires 1) the sequential phosphorylation of at least two serines on p47(PHOX): Ser-359 or Ser-370, followed by Ser-303 or Ser-304; and 2) the translocation of p47(PHOX) to the membrane at some point after the first phosphorylation takes place.

Arachidonic Acid↗

PubMed1998

A prospective study of community-acquired bloodstream infections among febrile adults admitted to Mulago Hospital in Kampala, Uganda.

Septicemia is a frequent cause of death in HIV-infected adults in developing countries. Additional prospective studies are needed to determine the etiology of bloodstream infections (BSI) in febrile HIV-infected adults and guide initial evaluation and treatment in this setting. We assessed the prevalence and etiology of community-acquired BSI among 299 consecutive febrile adult medical admissions to Mulago Hospital, Kampala, Uganda, over a 4-month period in 1997. The median age of our patients was 30 years, 159 (53%) were male, and 227 (76%) HIV-1-seropositive. Overall, prevalence of bacteremia or fungemia (1 patient) was 24%. Bacteremia was more frequent in HIV-infected than in uninfected patients (27% versus 15%, respectively; p = .04). Mycobacterium tuberculosis (n = 28), Streptococcus pneumoniae (n = 15) and Salmonella species (n = 13) were the most frequent isolates. All Salmonella and mycobacterial isolates were recovered from HIV-infected patients. Pneumococcal bacteremia was not associated with HIV seropositivity. M. avium complex and M. simiae were isolated from two HIV-infected patients. The rate of mycobacteremia among febrile HIV-infected adults presenting for hospitalization was 13%. Bacteremia and disseminated tuberculosis are frequent causes of morbidity in febrile HIV-infected Ugandan adults. Initial empiric antibiotic coverage in this setting should be targeted toward the pneumococcus and gram-negative enteric bacilli, especially nontyphi Salmonella species. All patients presenting with chronic cough should be evaluated for tuberculosis.

Adolescent↗

PubMed1998

Human sulfite oxidase R160Q: identification of the mutation in a sulfite oxidase-deficient patient and expression and characterization of the mutant enzyme.

Sulfite oxidase catalyzes the terminal reaction in the degradation of sulfur amino acids. Genetic deficiency of sulfite oxidase results in neurological abnormalities and often leads to death at an early age. The mutation in the sulfite oxidase gene responsible for sulfite oxidase deficiency in a 5-year-old girl was identified by sequence analysis of cDNA obtained from fibroblast mRNA to be a guanine to adenine transition at nucleotide 479 resulting in the amino acid substitution of Arg-160 to Gln. Recombinant protein containing the R160Q mutation was expressed in Escherichia coli, purified, and characterized. The mutant protein contained its full complement of molybdenum and heme, but exhibited 2% of native activity under standard assay conditions. Absorption spectroscopy of the isolated molybdenum domains of native sulfite oxidase and of the R160Q mutant showed significant differences in the 480- and 350-nm absorption bands, suggestive of altered geometry at the molybdenum center. Kinetic analysis of the R160Q protein showed an increase in Km for sulfite combined with a decrease in kcat resulting in a decrease of nearly 1,000-fold in the apparent second-order rate constant kcat/Km. Kinetic parameters for the in vitro generated R160K mutant were found to be intermediate in value between those of the native protein and the R160Q mutant. Native sulfite oxidase was rapidly inactivated by phenylglyoxal, yielding a modified protein with kinetic parameters mimicking those of the R160Q mutant. It is proposed that Arg-160 attracts the anionic substrate sulfite to the binding site near the molybdenum.

Child, Preschool↗

PubMed1998

Activation of the leukocyte NADPH oxidase by phorbol ester requires the phosphorylation of p47PHOX on serine 303 or 304.

The leukocyte NADPH oxidase is an enzyme in phagocytes and B lymphocytes that when activated catalyzes the production of O-2 from oxygen and NADPH. During oxidase activation, serine residues in the C-terminal quarter of the oxidase component p47(PHOX) become extensively phosphorylated, the protein acquiring as many as 9 phosphate residues. In a study of 11 p47(PHOX) mutants, each containing an alanine instead of a serine at a single potential phosphorylation site, we found that all but S379A corrected the defect in O-2 production in Epstein-Barr virus (EBV)-transformed p47(PHOX)-deficient B cells (Faust, L. P., El Benna, J., Babior, B. M., and Chanock, S. J. (1995) J. Clin. Invest. 96, 1499-1505). In particular, O-2 production was restored to these cells by the mutants S303A and S304A. Therefore, apart from serine 379, whose state of phosphorylation in the activated oxidase is unclear, no single potential phosphorylation site appeared to be essential for oxidase activation. We now report that the double mutant p47(PHOX) S303A/S304A was almost completely inactive when expressed in EBV-transformed p47(PHOX)-deficient B cells, even though it was expressed in normal amounts in the transfected cells and was able to translocate to the plasma membrane when the cells were stimulated. In contrast, the double mutant p47(PHOX) S303E/S304E was able to support high levels of O-2 production by EBV-transformed p47(PHOX)-deficient B cells. The surprising discovery that the double mutant S303K/S304K was also able to support considerable O-2 production suggests either that the effect of phosphorylation is related to the increase in hydrophilicity around serines 303 and 304 or that activation involves the formation of a metal bridge between the phosphorylated serines and another region of the protein.

B-Lymphocytes↗

PubMed1998

Adenovirus-mediated gene transfer of the human TIMP-1 gene inhibits smooth muscle cell migration and neointimal formation in human saphenous vein.

Neointimal formation involving smooth muscle cell (SMC) migration and proliferation is a common feature of atherosclerosis, restenosis after angioplasty, and vein graft intimal thickening. Extracellular matrix remodeling by metalloproteinase (MMP) enzymes is an essential component of neointimal formation and therefore MMPs are a potential target for localized gene therapy. To evaluate this concept using human tissue, we used the highly reproducible organ culture model of neointimal formation in human saphenous vein to investigate the effect of adenovirus-mediated gene transfer of tissue inhibitor of metalloproteinase 1 (TIMP-1) and the bacterial LacZ gene (RAd35) as a control. Incubating veins with 100 microl of RAd35 (1.2 x 10(10) pfu/ml) led to expression of LacZ in 39 +/- 7% of surface cells but had no effect on SMC proliferation, migration, or neointimal formation. Similar infection with RAdTIMP-1 increased explanation of TIMP-1 in surface cells and significantly inhibited neointimal formation and SMC migration after 14 days by 54% and 78%, respectively (n = 6, p < 0.05 Student's paired t test). No effect on SMC proliferation or deleterious effect on cell viability was observed. A specific MMP inhibitory effect was detected using in situ zymography. These data confirm the importance of MMPs in neointimal formation and highlight the potential for application of TIMP gene therapy.

Adenoviridae↗

PubMed1998

Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model.

Transfusion-related acute lung injury (TRALI) is a serious complication of hemotherapy. During blood storage, lipids are generated and released into the plasma. In this study, the role of these lipids in TRALI was investigated using an isolated, perfused rat lung model. Rats were pretreated with endotoxin (LPS) or saline in vivo and the lungs were isolated, ventilated, and perfused with saline, or (a) 5% (vol/ vol) fresh human plasma, (b) plasma from stored blood from the day of isolation (D.0) or from the day of outdate (D.42), (c) lipid extracts from D.42 plasma, or (d) purified lysophosphatidylcholines. Lungs from saline or LPS-pretreated rats perfused with fresh (D.0) plasma showed no pulmonary damage as compared with saline perfused controls. LPS pretreatment/D.42 plasma perfusion caused acute lung injury (ALI) manifested by dramatic changes in both pulmonary artery pressure and edema. Incubation of LPS pre-tx rats with mibefradil, a Ca2+ channel blocker, or WEB 2170, a platelet-activating factor (PAF) receptor antagonist, inhibited ALI caused by D.42 plasma. Lung histology showed neutrophil sequestration without ALI with LPS pretreatment/saline or D.0 plasma perfusion, but ALI with LPS pretreatment/D.42 plasma perfusion, and inhibition of D.42 plasma induced ALI with WEB 2170 or mibefradil. A significant increase in leukotriene E4 was present in LPS-pretreated/D.42 plasma-perfused lungs that was inhibited by WEB 2170. Lastly, significant pulmonary edema was produced when lipid extracts of D.42 plasma or lysophosphatidylcholines were perfused into LPS-pretreated lungs. Lipids caused ALI without vasoconstriction, except at the highest dose employed. In conclusion, both plasma and lipids from stored blood produced pulmonary damage in a model of acute lung injury. TRALI, like the adult respiratory distress syndrome, may be the result of two insults: one derived from stored blood and the other from the clinical condition of the patient.

Acute Disease↗

PubMed1998

The leukocyte NADPH oxidase subunit p47PHOX: the role of the cysteine residues.

The leukocyte NADPH oxidase is a multi-subunit enzyme that catalyzes the reduction of oxygen to O2- at the expense of a reduced pyridine nucleotide. We have used site-directed mutagenesis to examine the functional role of the four cysteines in p47PHOX, one of the subunits of the oxidase. For these experiments, mutant proteins in which a single cysteine was replaced with alanine were expressed in p47PHOX-deficient Epstein-Barr virus-transformed B lymphoblasts, and O2- production by these transfected cells was measured. The activity of the mutant C98A was similar to that of wild type, but the maximum rate of O2- production by C196A was significantly larger than seen with wild type. The other two mutants (i.e., C111A and C378A) differed from wild type not only in maximum O2- production, but also in the time required for activation, which was considerably delayed with both of these mutants. The similarity in the time courses of oxidase activation with the C111A and C378A mutants, and the finding that C378A occurs in the sequence CSE, raises the possibility that these cysteines may be involved in redox regulation of oxidase activity.

B-Lymphocytes↗

PubMed1998

New mechanisms by which secretory phospholipase A2 stimulates neutrophils to provoke the release of cytotoxic agents.

BACKGROUND: Secretory phospholipase A2 (sPLA2) is a potent proinflammatory enzyme that stimulates inflammation through the production of reactive lipids. However, enzymatic inhibitors have been disappointing in their effectiveness in halting hyperinflammation. OBJECTIVE: To determine whether sPLA2 acts directly on neutrophil plasma membrane lipids or via a nonenzymatic mechanism. DESIGN: Isolated neutrophils (PMNs) were incubated with 3 types of sPLA2, and elastase and superoxide release from PMNs was measured. Ethyleneglycotetraacetic acid was used as a selective enzymatic inhibitor. The PMNs were exposed to sPLA2 in the presence and absence of ethyleneglycotetraacetic acid and the release of elastase was measured. SETTING: Urban trauma research laboratory. PATIENTS: Normal healthy donors of PMNs. MAIN OUTCOME MEASURES: Stimulated release of superoxide and elastase. RESULTS: The sPLA2 acted directly on plasma membrane lipids to stimulate the PMN to produce superoxide and release elastase. This mechanism is blocked with enzymatic inhibition of sPLA2. The sPLA2 also provokes elastase release from PMNs independently of its enzymatic function. This mechanism is not blocked with traditional enzymatic inhibitors. CONCLUSIONS: These data indicate that the sPLA2 can act directly on PMNs to stimulate the release of inflammatory mediators via enzymatic degradation of plasma membrane lipids. In addition, sPLA2 can act as a ligand and stimulate the PMN independently of its enzymatic activity.

Animals↗

PubMed1998

Interleukin-6 augments neutrophil cytotoxic potential via selective enhancement of elastase release.

BACKGROUND: Interleukin-6 (IL-6) appears to be a reliable marker of disease severity in critically ill patients at risk for inflammatory organ injury such as ARDS and MOF. Debate continues, however, as to whether this pleiotropic cytokine acts principally as a proinflammatory or counterregulatory mediator. Because the polymorphonuclear leukocyte (PMN) is a central effector of inflammatory injury, defining the effects of IL-6 on mechanisms of PMN cytotoxicity may be revealing. Previous investigations of PMN release of reactive oxygen species demonstrate that IL-6 in concert with other mediators may augment cytotoxicity. We hypothesized that IL-6 alone increases PMN cytotoxic potential through selective enhancement of elastase release. MATERIALS AND METHODS: Isolated human PMNs were incubated with IL-6 in the physiologic range observed in critically ill patients (0.1 to 100 ng/ml) for 10 to 30 min. Selected cells were then activated with fMLP (1 microM). Elastase release was measured by specific cleavage of AAPV-pNA and compared to untreated cells and cells activated with formyl-Met-Leu-Phe (fMLP; 1 microM) alone. To determine if changes in elastase release might be due to IL-6 induced generation of PAF, WEB 2347 (50 microM) was preincubated with selected cells for 20 min. Surface expression of beta 2 integrins was measured by flow cytometry after incubating with labeled antibodies to CD11b and CD18. RESULTS: IL-6 alone at 100 ng/ml augmented basal elastase release by 116 +/- 41% within 10 min. Doses as low as 0.1 ng/ml stimulated elastase release when the incubation time was increased to 30 min. After 30 min of incubation, IL-6 at all doses examined augmented the elastase release of fMLP-activated cells (increases of 33 to 45%). WEB 2347 preincubation did not block augmentation of elastase release by IL-6 at 10 ng/ml. IL-6 had no effect on surface expression of beta 2 integrins at 10 ng/ml. CONCLUSIONS: IL-6 alone enhances both basal and fMLP-stimulated elastase release by PMNs. This proinflammatory action on PMNs may help explain the observed correlation between circulating IL-6 levels and inflammatory organ injury.

CD18 Antigens↗

PubMed1998

Primed neutrophils require phosphatidic acid for maximal receptor-activated elastase release.

BACKGROUND: Priming of neutrophils (PMNs) for protease release is believed to be central to the pathogenesis of PMN-mediated tissue injury observed in ARDS/MOF. Defining the intracellular signaling pathways involved with this excessive protease release may aid in establishing future therapies for ARDS. Phospholipase D (PLD) production of phosphatidic acid (PA) is thought to be pivotal in reactive oxygen species generation but its role in degranulation (i. e., protease release) remains unclear. Our hypothesis was that primed neutrophils require PLD production of PA for maximal activated release of elastase. METHODS: Isolated human PMNs were incubated with a well described antagonist of PA production, ethanol (ETOH, 100-1000 mg/dL), and then primed (PAF, 200 nM) followed by activation (fMLP, 1 microM). To mimic fMLP receptor-dependent activation, PMNs were primed and then directly activated with exogenous dioctanoyl l-alpha-phosphatidic acid (PA8, 0.5-200 microM). To confirm the importance of PA in elastase release, PA8 was given to primed-activated PMNs after ethanol pretreatment in an attempt to recover the maximal response. Elastase release was measured by the cleavage of AAPV-pNA. RESULTS: PA blockade with ETOH attenuated PAF-primed/fMLP-activated PMN elastase release in a dose-dependent manner. Exogenous PA8 reproduced maximally primed-activated PMN elastase release, and furthermore, PA8 was able to restore maximal elastase release following ethanol attenuation. CONCLUSIONS: Elastase release from PAF-primed/ fMLP-activated neutrophils is dependent on PA production. Thus, PA production appears to be involved in both oxidant-dependent and independent mechanisms of neutrophil cytotoxicity and may be a potential therapeutic target in the treatment of hyperinflammatory diseases such as ARDS/MOF.

Humans↗

PubMed1998

Resuscitation of the injured patient with polymerized stroma-free hemoglobin does not produce systemic or pulmonary hypertension.

BACKGROUND: Hemoglobin-based blood substitutes appear poised to deliver the promise of a universally compatible, disease-free alternative to banked blood. However, vasoconstriction following administration of tetrameric hemoglobins has been problematic, likely because of nitric oxide binding. Polymerized hemoglobin is effectively excluded from the abluminal space because of its size, and is thus less likely to perturb vasorelaxation. We therefore hypothesized that hemodynamic responses would be no different in injured patients receiving polymerized hemoglobin versus banked blood. METHODS: Injured patients requiring urgent transfusion were randomized to receive either polymerized hemoglobin or banked blood. Systemic arterial pressure, pulmonary arterial pressure, cardiac index, pulmonary capillary wedge pressure, systemic vascular resistance, and pulmonary vascular resistance were measured serially. RESULTS: There was no difference in any of the measured hemodynamic parameters between patients resuscitated with polymerized hemoglobin versus blood. CONCLUSIONS: Polymerized hemoglobin given in large doses to injured patients lacks the vasoconstrictive effects reported in the use of other hemoglobin-based blood substitutes. This supports the continued investigation of polymerized hemoglobin in injured patients requiring urgent transfusion.

Adult↗

PubMed1998

Paradoxical effects of resveratrol on the two prostaglandin H synthases.

Prostaglandin H synthase (PGHS) is the primary enzyme responsible for the biosynthesis of prostaglandins and thromboxanes. Of the two isoenzymes of PGHS, PGHS-1 is constitutively expressed and PGHS-2 is inducible by mitogens or other inflammatory stimuli. Constitutive expression of PGHS-2 in neoplastic tissues has been implicated in carcinogenesis. Resveratrol, a lignan, was recently shown to be an anticarcinogen that selectively inhibits PGHS-1. In vitro experiments to resolve these seemingly paradoxical observations revealed that resveratrol is not only an inhibitor of PGHS-1 but also is an activator of PGHS-2. Resveratrol non-competitively inhibited PGHS-1 with a K1 of 26 +/- 2 microM but enhanced the PGHS-2 activity nearly twofold. Additionally, resveratrol did not serve as a reducing co-substrate for the peroxidase activities of either enzyme despite being an easily oxidizable phenolic compound. Resveratrol inhibited the peroxidase activity of PGHS-1 (IC50 = 15 microM) better than that of PGHS-2 (IC50 = > 200 microM). Inhibition of the perxidase activity but not the cyclooxygenase activity of PGHS-2 resulted in the production of PGG2 from arachidonic acid. A plausible relationship between these observation and the anticarcinogenic activity of resveratrol is discussed.

Animals↗

PubMed1998

Living in a housing co-operative for low income women: issues of identity, environment and control.

The purpose of this study was to develop an understanding of how living on a low income affects the health of women and focused on the experiences of women living in a new housing co-operative built exclusively for unattached, low income women of middle age. Initially, the main focus of this study was the health beliefs, concerns, and practices of women living on a low income. As the study evolved, however, the experience of living in the housing co-operative was of such concern to the participants that the effects of housing on health came to have greater importance. A qualitative method was used based on Spradley's ethnographic method (Spradley, J. (1979). The ethnographic interview. Holt, Rinehart, and Winston, New York). Data included interviews with ten volunteer participants and field notes about these interviews and collection spanned a period of eight months. The major health issues that arose for the women focused around the concepts of the identity, environment and control. The women frequently mentioned aspects of the environment in regards to their health. The co-operative itself was an interesting environment with the potential to reduce the women's sense of isolation. The social context of the co-operative, however, was often cited as a source of stress rather than support. One of the most striking and unexpected findings of this study was that the women did not identify with one another. The women interviewed perceived themselves as a diverse group without a common identity. Finally, control emerged as a major theme underlining the women's perceptions of health. When asked to describe their lives, the women invariably began discussing coping strategies they used to manage on a low income. One woman actually made the connection between poverty and a lack of control by defining poverty as "having no options".

Adult↗