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Biomedical subjects

J R Allen

Publications and source records attributed to J R Allen.

At least 37 records · Page 2Linked to original sources

After the bombing: public scenarios and the construction of meaning.

In both our folk psychology and mental health practice, we adhere to the modernist view that a crisis is something that an individual has. A crisis is either something that happens to people or which people bring on themselves because of character pathology. On the other hand, postmodern theorists now draw our attention to how processes of interaction provide opportunities for certain characterizations to emerge and disipate. Both the conceptualization of an event as a crisis and the scenarios of how it is best understood arise within a community and emerge out of the communal construction of meaning. In this process in Oklahoma City, bystanders, politicians, pilgrims and news media played a role of great significance. Whether local or from afar, they became a community of observers who interacted with one another and looked to one another for verification as to what counted as a crisis and what behavior was appropriate. Lindy has observed that traumatized individuals are often surrounded quickly by a small network of trusted people who serve to buffer and protect them and who define what is helpful and what constitutes further trauma. Here, in Oklahoma, however, a wider public defined the event as a crisis, elaborated on it, and have gradually transformed it into almost mythic proportions, a process now exemplified in the construction of the Oklahoma City National Monument. However, they have also endorsed diverse other scenarios, not all of which have facilitated appropriate grieving, repair of life-disruption, or moving on. All, however, seem to have given a sense of meaning to the event. In this rich matrix, some survivors and their families have felt helped. Others have felt exploited. Still others have wanted to forget the whole thing and to avoid anything that reminded them of it. Of the would-be helpers, some felt unjustly rejected and unappreciated. Others felt appreciated, useful, and even enriched. However, a true legacy of the bombing may well be the metalogue it can precipitate and advance about the relationship between individuals and society, and especially the relationship between our individual life-stories and larger public scenarios, and the effects these scenarios have on the questions we can ask, what we can perceive and what solutions we can create.

Crime Victims↗

Long- and short-looking infants' recognition of symmetrical and asymmetrical forms.

Adults process symmetrical visual forms more rapidly than asymmetrical visual forms, presumably because symmetrical forms are amenable to a global visual encoding strategy. Individual differences in look duration during infancy have been hypothesized to covary with different modes of visual intake and encoding, with longer look durations reflecting encoding based on prolonged inspection of local visual properties, and briefer look durations reflecting encoding based on more of a global, or global-to-local processing sequence. This hypothesis predicts that short-looking infants would process symmetrical stimuli faster than asymmetrical stimuli, but that long-looking infants would not. Three experiments are described here in which this prediction is tested. Results were in general accord with the prediction, and provide further support for the hypothesis that individual differences in look duration may reflect different modes of visual encoding or inspection.

Analysis of Variance↗

New roles for CO2 in the microbial metabolism of aliphatic epoxides and ketones.

Short-chain aliphatic epoxides and ketones are two classes of toxic organic compounds formed biogenically and anthropogenically. In spite of their toxicity, these compounds are utilized as primary carbon and energy sources or are generated as intermediate metabolites in the metabolism of other compounds (e.g., alkenes, alkanes, and secondary alcohols) by a number of diverse bacteria. One bacterium capable of using both classes of compounds is the gram-negative aerobe Xanthobacter strain Py2. Studies of epoxide and ketone (acetone) metabolism by Xanthobacter strain Py2 have revealed a central role for CO2 in these processes. Both classes of compounds are metabolized by carboxylation reactions that produce beta-keto acids as products. The epoxide- and ketone-converting enzymes are distinct carboxylases with molecular properties and cofactor requirements unprecedented for other carboxylases. Epoxide carboxylase is a four-component multienzyme complex that requires NADPH and NAD+ as cofactors. In the course of epoxide carboxylation, a transhydrogenation reaction occurs wherein NADPH undergoes oxidation and NAD+ undergoes reduction. Acetone carboxylase is a multimeric (three-subunit) ATP-dependent enzyme that forms AMP and inorganic phosphate as ATP hydrolysis products in the course of acetone carboxylation. Recent studies have demonstrated that acetone metabolism in diverse anaerobic bacteria (sulfate reducers, denitrifiers, phototrophs, and fermenters) also proceeds by carboxylation reactions. ATP-dependent acetone carboxylase activity has been demonstrated in cell-free extracts of the anaerobic acetone-utilizers Rhodobacter capsulatus, Rhodomicrobium vannielii, and Thiosphaera pantotropha. These studies have identified new roles for CO2 as a cosubstrate in the metabolism of two classes of important xenobiotic compounds. In addition, two new classes of carboxylases have been identified, the investigation of which promises to reveal new insights into biological strategies for the fixation of CO2 to organic substrates.

Acetone↗

Clinical research: assessing the future in a changing environment; summary report of conference sponsored by the American Medical Association Council on Scientific Affairs, Washington, DC, March 1996.

Concerns about funding of clinical research underlie all other problems identified at the Council on Scientific Affairs conference. Future National Institutes of Health (NIH) budgets are likely to be constant at best, and the general public expects cost containment to be an ongoing goal; this is exacerbated by the impending Medicare Trust Fund crisis. Meanwhile, traditional financial support of clinical research in academic medical centers (AMCs) through cross-subsidization is imperiled by competitive pressures largely caused by managed care. Although managed care organizations (MCOs) are potentially rich sources of funding and other resources, and some not-for-profit companies are conducting some research, for-profit MCOs have not demonstrated an understanding of the importance of clinical research. Young physicians are being discouraged from careers as clinical researchers and established investigators are "dropping out" because of demands for clinical productivity and competition for research grants, loss of patients/research subjects to managed care, perceived lack of status and compensation, and overall uncertainty about continued financial support. Efforts to assist current and potential clinical investigators are discussed in this report. Loss of patients, denial of reimbursement, and competition with MCOs and contract research organizations (CROs) have placed AMCs under unprecedented pressure. However, research centers located in AMCs have allowed investigators to conduct clinical research by providing a "protected environment." Furthermore, many AMCs are determined to continue conducting clinical research and are addressing related problems. Although the NIH will continue to be a major source of funding for clinical research, partnerships between various private and public entities provide important opportunities to maximize the productivity of all individuals and institutions involved. Potential partnerships include MCOs, AMCs, CROs, pharmaceutical companies and other industry, the Department of Defense, the Veterans Health Administration, practice-based physicians, and private foundations and patient support groups. "Partnerships in advocacy" for clinical research will be essential. Efforts to recruit for-profit MCOs to the clinical research endeavor identified in this report include (1) emphasizing issues of interest to them (eg, outcomes research); (2) stressing the significance of some research to the marketplace; (3) developing criteria to distinguish individual MCOs on the basis of their contribution to the public interest; (4) equating money spent on research with "R&D dollars" spent in nonmedical business enterprises; and (5) educating purchasers of health care (eg, corporate health plan directors) about clinical research. Conducting clinical research in all managed care settings requires leadership, the understanding and cooperation of physicians and support staff, wise use of limited resources (ie, funding only the best research projects), sound methodology, and above all, the perception that the research will ultimately improve patient care.

American Medical Association↗

Invasive aspergillosis in severely neutropenic patients over 18 years: impact of intranasal amphotericin B and HEPA filtration.

The impact of intranasal amphotericin B and high-efficiency particulate air (HEPA) filtration on the incidence of invasive aspergillosis was reviewed in patients from 1977 to 1994 undergoing intensive chemotherapy. Overall, the incidence of proven invasive aspergillosis was reduced from 24.4% (1977-1984) to 7.1% (1985-1991) (P < 0.001) following the introduction of intranasal prophylaxis, but when probable cases of aspergillosis were included and lymphoma cases excluded, there was no change in incidence. Following the introduction of HEPA filtration, patient exposure to aspergillus spores as measured by air sampling was markedly reduced and there were no new cases of invasive aspergillosis. HEPA filtration proved effective in reducing invasive aspergillosis and has allowed increasingly aggressive treatment regimens to be introduced.

Administration, Intranasal↗

Crossover use of donated blood for autologous transfusion: report of the Council on Scientific Affairs, American Medical Association.

BACKGROUND: Controversy exists concerning whether the costs and potential risks outweigh the potential benefits of "crossover" use in the general blood supply of unutilized blood that was donated for autologous transfusion. STUDY DESIGN AND METHODS: Published articles and reports were identified through systematic search of MEDLINE and review of references cited in previously identified articles, textbooks, and reports. Consultation was made with experts in blood donation and transfusion. Additional peer review was received from the American Medical Association (AMA) Council on Scientific Affairs RESULTS: Concern over infectious disease transmission has led to increased interest in and support for autologous transfusion for individuals having planned surgeries. Different requirements exist for collection, labeling, and screening of blood to be used for autologous versus allogeneic transfusions; therefore, procedures for diverting autologous blood donations to the general blood supply involve considerable expense. Several cost-effectiveness studies of autologous blood donation and transfusion conclude that currently this "crossover" appears to be an expensive procedure yielding little increased benefit from a societal perspective. CONCLUSIONS: The recommendations in this report were adopted as AMA Policy at the AMA Annual Meeting in June 1997. The AMA does not encourage blood collection programs to "cross over" units donated for autologous use to the allogeneic blood supply. Practice guidelines are needed, and should be utilized to ensure parsimony in the use of autologous blood donations and transfusions.

Blood Donors↗

Identification and characterization of epoxide carboxylase activity in cell extracts of Nocardia corallina B276.

The metabolism of aliphatic epoxides (epoxyalkanes) by the alkene-utilizing actinomycete Nocardia corallina B276 was investigated. Suspensions of N. corallina cells grown with propylene as the carbon source readily degraded propylene and epoxypropane, while suspensions of glucose-grown cells did not. The addition of propylene and epoxypropane to glucose-grown cells resulted in a time-dependent increase in propylene- and epoxypropane-degrading activities that was prevented by the addition of rifampin and chloramphenicol. The expression of alkene- and epoxide-degrading activities was correlated with the high-level expression of several polypeptides not present in extracts of glucose-grown cells. Epoxypropane and epoxybutane degradation by propylene-grown cell suspensions of N. corallina was stimulated by the addition of CO2 and inhibited by the depletion of CO2. Cell extracts catalyzed the carboxylation of epoxypropane to form acetoacetate in a reaction that was dependent on the addition of CO2, NAD+, and a reductant (NADPH or dithiothreitol). In the absence of CO2, epoxypropane was isomerized by cell extracts to form acetone at a rate approximately 10-fold lower than the rate of epoxypropane carboxylation. Methylepoxypropane was found to be a time-dependent, irreversible inactivator of epoxyalkane-degrading activity. These properties demonstrate that epoxyalkane metabolism in N. corallina occurs by a carboxylation reaction forming beta-keto acids as products and provide evidence for the involvement in this reaction of an epoxide carboxylase with properties and cofactor requirements similar to those of the four-component epoxide carboxylase enzyme system of the gram-negative bacterium Xanthobacter strain Py2 (J. R. Allen and S. A. Ensign, J. Biol. Chem. 272:32121-32128, 1997). The addition of epoxide carboxylase component I from Xanthobacter strain Py2 to methylepoxypropane-inactivated N. corallina extracts restored epoxide carboxylase activity, and the addition of epoxide carboxylase component II from Xanthobacter Py2 to active N. corallina extracts stimulated epoxide isomerase rates to the same levels observed with the purified Xanthobacter system. Antibodies raised against Xanthobacter strain Py2 epoxide carboxylase component I cross-reacted with a polypeptide in propylene-grown N. corallina extracts with the same molecular weight as component I but did not cross-react with glucose-grown extracts. Together, these results suggest a common pathway of epoxyalkane metabolism for phylogenetically distinct bacteria that involves CO2 fixation and the activity of a multicomponent epoxide carboxylase enzyme system.

Alkenes↗

Adequacy of CPD: comparing Kt/V and creatinine clearance.

Presently, adequate dialysis in continuous peritoneal dialysis (CPD) patients is assessed by monitoring urea kinetics (Kt/V) or by measuring the total creatinine clearance (CC). Target Dialysis Outcome Quality Initiative (DOQI) goals are a weekly Kt/V of at least 2.0, and a CC of at least 60 L/wk per 1.73 m2. One hundred and four CPD patients in the New Haven continuous ambulatory peritoneal dialysis (CAPD) unit had their most recent Kt/V and CC reviewed. Of these patients, 58.7% attained the DOQI goals for Kt/V and CC, 14.4% had an acceptable Kt/V but low CC, 11.5% had an acceptable CC but low Kt/V, and 15.4% had both low Kt/V and low CC. A CC > 60 L/week per 1.73 m2 was associated with a residual renal function of > 25 L/wk per 1.73 m2. For a Kt/V of > 2.0, good residual renal function was helpful but not essential. A question left unanswered is whether patients with a low Kt/V and an adequate CC or low CC and acceptable Kt/V need more dialysis.

Creatinine↗

The effects of linear acceleration on distortion product otoacoustic emissions in human ears.

BACKGROUND: The effect of high levels of linear acceleration (G) on the cochlea has never been studied prospectively. HYPOTHESIS: Linear acceleration at high levels has no effect on the human cochlea as demonstrated by a comparison of pre- and post-exposure measurements. METHODS: There were 22 healthy volunteers who underwent exposure to up to 9 G in a military aviation training centrifuge. Prior to exposure they were screened for cochleovestibular disorders and underwent tympanometry, audiometry and distortion product otoacoustic emissions testing (DPOAE). Immediately after exposure, they underwent serial testing of each of these parameters until they returned to baseline. RESULTS: There was no significant change in tympanometry in any subject. Audiometry revealed a temporary threshold shift of 30 db at 6 kHz in one ear of a single subject. This was accompanied by a complete loss of DPOAE at the same frequency. DPOAE did not return to baseline at 2 weeks even though the audiogram had reverted to baseline by 8 d. Four other ears displayed significant losses of emissions at single frequencies without an accompanying change on the audiogram. CONCLUSIONS: This study demonstrates that accelerative stress may cause transient injury to the cochlea. The mechanism of injury due to acceleration is probably ischemia, although a purely mechanical effect on the outer hair cells cannot be precluded. These data also reinforce a growing body of evidence that demonstrates the greater sensitivity of DPOAE over psychoacoustic testing in detecting early or subclinical cochlear damage.

Acceleration↗

Stressors and development: a reciprocal relationship.

In this article we have attempted to delineate the importance of developmental levels in a young person's response to stressors and, conversely, the effect of stressors on levels of development. In so doing, we isolated specific lines of development from their context. We neglected the important roles of rewards and punishments, permissions and prohibitions, family and community dynamics, values, stories and myths. Even in this simplified schema, we have not addressed the importance of protective and risk factors, neither of which are found in isolation; but all of these issues are the subject of articles elsewhere in this issue.

Adolescent↗

Of resilience, vulnerability, and a woman who never lived.

One day we may be able to say with some degree of confidence that Factor A over a certain level + Factor B over a certain level + Factor C under a certain level + Factor X will produce Y level of functioning in domain X--in about 80% of cases. Despite advances in our knowledge about the influence of various protective and risk factors in development, health, and functioning, however, we still have good reason to remain humble. This article examines some of the advances and some of the problems in the study of resilience and vulnerability in children and adolescents.

Adolescent↗

Stress in children exposed to violence. Reenactment and rage.

Violence is a major public health problem that increasingly involves children and adolescents as both victims and witnesses. Exposure to violence is now implicated in the development of stress conditions. This article uses Terr's typology to describe responses to various kinds of violence and suggests that the posttraumatic stress model adds a unique dimension to our understanding of the effects of violence on children and adolescents.

Adolescent↗

What if Astyanax had survived? War, children, and youth.

What, then, might have happened to Astyanax had he survived? He might have become a Greek slave and accepted his lot, or he might have felt loyalty and an obligation to his Trojan ancestry and organized acts of revenge. Depending on his personal characteristics and the people and the community that raised him, a number of outcomes are possible. The fact that after 3000 years we know little more than did the Homeric bards, however, gives us reason to be humble. There is evidence that each experience of loss or violence is additive and reduces coping ability. Although the psychologic disturbances of children and youth exposed to war do appear less intense than might have been expected, as Garmezy and Rutter noted in 1985, it is impossible to know the cost, the vulnerabilities that have been veiled, and what might have been. Perhaps the most remarkable thing is how some children seem able to transcend their misfortunes and even to be steeled by them. Coles has recorded how a 6-year-old, African-American girl, initiating school desegregation in New Orleans in the face of mob violence and daily threats to her life, told him that if she managed to get through with some success, she had an explanation: "It will be because there is more to me than I ever realized."

Adolescent↗

Purification to homogeneity and reconstitution of the individual components of the epoxide carboxylase multiprotein enzyme complex from Xanthobacter strain Py2.

Epoxide metabolism in the aerobic bacterium Xanthobacter strain Py2 proceeds by an NADPH- and NAD+-dependent carboxylation reaction that forms beta-keto acids as products. Epoxide carboxylase, the enzyme catalyzing this reaction, was resolved from the soluble fraction of cell-free extracts into four protein components that are obligately required for functional reconstitution of epoxide carboxylase activity. One of these components, component II, has previously been purified and characterized as an NADPH:disulfide oxidoreductase. In the present study, the three additional epoxide carboxylase components have been purified to homogeneity and characterized. These component proteins are as follows: component I, a homohexameric protein consisting of 41.7-kDa subunits; component III, a dimeric protein consisting of 26.0- and 26.2-kDa polypeptides; and component IV, a dimeric protein consisting of a single 25.4-kDa polypeptide. Component I contained 5 mol of tightly bound zinc per mol of protein. Component I was specifically inactivated by methylepoxypropane, a time-dependent irreversible inactivator of epoxide carboxylase activity, suggesting that this component plays an integral role in epoxide binding and activation. No metals or organic cofactors were detected for components III and IV. The molecular weights, N-terminal sequences, and amino acid compositions of the purified epoxide carboxylase components were determined and found to correlate with open reading frames within and adjacent to a cloned fragment of DNA that complements Xanthobacter Py2 mutants defective in epoxide degradation. Using the purified epoxide carboxylase system, epoxide carboxylation was found to be stoichiometrically coupled to the transhydrogenation of pyridine nucleotide cofactors according to the following equation: epoxypropane + CO2 + NADPH + NAD+ --> acetoacetate + H+ + NADP+ + NADH.

Carboxy-Lyases↗

Characterization of three protein components required for functional reconstitution of the epoxide carboxylase multienzyme complex from Xanthobacter strain Py2.

Epoxide carboxylase from Xanthobacter strain Py2 catalyzes the reductant- and NAD+-dependent carboxylation of aliphatic epoxides to beta-keto acids. Epoxide carboxylase from Xanthobacter strain Py2 has been resolved from cell extracts by anion-exchange chromatography into three protein components, designated I, II, and III, that are obligately required for functional reconstitution of epoxide carboxylase activity. Component II has been purified to homogeneity on the basis of its ability to complement components I and III in restoring epoxide carboxylase activity. Purified component II had a specific activity for epoxide carboxylation of 41.8 mU x min(-1) x mg(-1) when components I and III were present at saturating levels. The biochemical properties of component II reveal that it is the flavin-containing NADPH:disulfide oxidoreductase that was recently shown by other means to be associated with epoxide degradation activity in Xanthobacter strain Py2 (J. Swaving, J. A. M. de Bont, A. Westphal, and A. Dekok, J. Bacteriol. 178:6644-6646, 1996). The rate of epoxide carboxylation was dependent on the relative concentrations of the three carboxylase components. At fixed concentrations of two of the components, epoxide carboxylation rates were saturated in a hyperbolic fashion by increasing the concentration of the third variable component. Methylepoxypropane has been characterized as a time-dependent, irreversible inactivator of epoxide carboxylase activity that is proposed to be a mechanism-based inactivator of the enzyme. The addition of component I, but not that of component II or III, to methylepoxypropane-inactivated cell extracts restored epoxide carboxylase activity, suggesting that component I contains the epoxide binding and activation sites.

Bacterial Proteins↗

Effect of surface-attached heparin on the response of potassium-selective electrodes.

Heparin (or hydrolyzed heparin) was covalently attached on the surface of derivatized cellulose triacetate membranes, which were subsequently impregnated with the potassium-selective ionophore valinomycin. The resulting ion-selective electrodes presented near-Nernstian response to potassium and had selectivity coefficients of the same order of magnitude as those of conventional poly-(vinyl chloride)-based electrodes. It was found that the heparin layer does not alter significantly the response characteristics of the electrodes. The biological activity of the immobilized heparin (or hydrolyzed heparin) was measured in terms of its inactivation of blood coagulation factor Xa. It was found that the covalently anchored hydrolyzed heparin was not biologically active, but the immobilized heparin was able to inactivate factor Xa. Therefore, by covalently attaching heparin on the surface of ion-selective electrodes, electrodes with improved blood compatibility characteristics may be prepared.

Cellulose↗