Linking mental health and violence prevention.
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Biomedical subjects
Publications and source records attributed to T Smith.
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Background characterization of assault-related injuries have demonstrated that lifestyle, substance abuse, education, employment, mental illness, and high-risk behavior contribute to low self-esteem in repeat assault victims. Recurrent-assault patients have never been studied with respect to self-esteem. This study evaluated self-esteem and assault-related injury in 28 consecutive male assault patients (11 first-assault and 17 recurrent-assault patients) and 19 controls with no previous assault history. Study participants were administered the Walmyr Assessment Scales Index of Self-Esteem (WASISE) as part of a three-item survey to determine the relationship between self-esteem and assault-related injury. No demographic differences were found between the groups. The mean (+/- standard error) WASISE score for recurrent-assault patients (34.9 +/- 3.4) was significantly higher than mean scores for no-assault and first-time assault-injured patients (14.7 +/- 1.4 and 15.0 +/- 2.3, respectively). The recurrent-assault patients had a lower mean education level than both no-assault and first-time assault-injured patients (2.1 +/- 0.26 and 1.9 +/- 0.57, respectively). Eighteen (2%) first-time assault-injured and 11 (7%) recurrent-assault patients were employed. These data suggest that self-esteem, education, and employment history need to be considered when evaluating and developing interventions for repeat-assault patients.
BACKGROUND: Peripheral blood eosinophilia is a particularly early and specific marker of both renal and hepatic allograft rejection. Therefore we evaluated the relationship between blood eosinophil counts and cardiac and pulmonary allograft rejection. METHODS: Differential blood counts were available within 3 days before 383 endomyocardial biopsy specimens in 56 heart transplant recipients. Blood counts were also available before 84 treated rejection episodes and 28 transbronchial biopsy specimens showing no rejection in 58 lung transplant recipients. RESULTS: Cardiac allograft rejection: There was a significant association between the mean maximum blood eosinophil count and treated acute rejection (p < 0.01) and a linear relationship between this eosinophil count and the histologic grade of rejection (p < 0.01). The first increase in eosinophils occurred at a median of 4 days before treated rejection. Pulmonary allograft rejection: The mean maximum blood eosinophil count was 0.14 x 10(9)/L (95% confidence interval = 0.10, 0.18) preceding treated rejection, and this was significantly greater than the mean maximum blood eosinophil count of 0.07 x 10(9)/L (confidence interval = 0.05, 0.09) measured when there was no rejection or during infection (p = 0.01). The first increase in eosinophil occurred at a median of 5 days before treated rejection. There was no relationship between blood neutrophil counts and either cardiac or pulmonary allograft rejection. CONCLUSIONS: An increase in peripheral blood eosinophils but not neutrophils is a specific and early marker of clinically significant rejection of both cardiac and pulmonary allografts. Furthermore, the maximum blood eosinophil count measured in the 3 days before rejection is linearly related to the severity of cardiac allograft rejection.
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The mRNA encoding an agouti related protein (ART) of unknown biochemical function was previously reported to be up-regulated in the hypothalamus of two genetically obese mouse strains. We have expressed human ART as a secreted protein in COS-7 cells, and show that recombinant ART is functionally active in inhibiting the binding of a radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) analog to the human melanocortin-3 (MC-3) and melanocortin-4 (MC-4) receptors, while it is not a potent inhibitor of the human melanocortin-5 (MC-5) receptor. ART is an antagonist of the human MC-3 and MC-4 receptors as determined in functional assay. ART appears to be approximately 100-fold more potent than agouti with reference to the MC-3R and MC-4R binding affinity. These data suggest that ART may be a physiological regulator of feeding behavior.
The ability to recognize individual animals has substantially increased our knowledge of the biology and behaviour of many taxa. However, not all species lend themselves to this approach, either because of insufficient phenotypic variation or because tag attachment is not feasible. The use of genetic markers ('tags') represents a viable alternative to traditional methods of individual recognition, as they are permanent and exist in all individuals. We tested the use of genetic markers as the primary means of identifying individuals in a study of humpback whales in the North Atlantic Ocean. Analysis of six microsatellite loci among 3,060 skin samples collected throughout this ocean allowed the unequivocal identification of individuals. Analysis of 692 'recaptures', identified by their genotype, revealed individual local and migratory movements of up to 10,000 km, limited exchange among summer feeding grounds, and mixing in winter breeding areas, and also allowed the first estimates of animal abundance based solely on genotypic data. Our study demonstrates that genetic tagging is not only feasible, but generates data (for example, on sex) that can be valuable when interpreting the results of tagging experiments.
The present study investigated the interactions between cytochrome P450 (P450) enzymes and the NADPH:cytochrome oxidoreductase (OR) in the microsomal membrane. Microsomes containing human cytochrome P450 2A6 (h2A6) coexpressed with human OR (hOR) via a baculovirus expression system displayed coumarin hydroxylase activity with apparent Km and Vmax values of 0.41 microM and 4.05 nmol/min/nmol P450, respectively. Incorporation of purified rat liver cytochrome b5 (b5) into the microsomes increased the Vmax 2.5-fold, but did not affect the Km. The N-nitrosodimethylamine (NDMA) demethylase activity of human cytochrome P450 2E1 (h2E1) coexpressed similarly was characterized previously. Coumarin was shown not to be a substrate nor an inhibitor of h2E1, and NDMA was not a substrate nor an inhibitor of h2A6. In microsomes containing h2A6, h2E1, and hOR (M-h2A6-h2E1-hOR) obtained from a triple expression system, the two P450 enzymes were shown to compete with each other for interaction with hOR. In incubations with M-h2A6-h2E1-hOR, the presence of a h2A6 substrate (coumarin) decreased NDMA demethylase activity by a maximum of 47%, and the presence of a h2E1 substrate (NDMA) decreased coumarin hydroxylase activity by a maximum of 19%. This substrate-induced competition between h2A6 and h2E1 was decreased by the addition of purified b5. In the absence of a substrate, the NADPH-dependent H2O2 formation was high in both M-h2A6-h2E1-hOR and M-h2E1-hOR, but low in M-h2A6-hOR. The addition of NDMA had little effect on the H2O2 formation in M-h2A6-h2E1-hOR and M-h2E1-hOR. The addition of coumarin, however, slightly decreased H2O2 formation in M-h2A6-h2E1-hOR, but drastically increased H2O2 formation in M-h2A6-hOR. These results suggest that the presence of a h2A6 substrate decreased the electron flow to h2E1 in M-h2A6-h2E1-hOR. The activities of coumarin hydroxylase and NDMA demethylase of M-h2A6-h2E1-hOR were decreased and increased, respectively, by an increase in ionic strength. The ionic strength, however, did not drastically change the substrate-induced competition between h2A6 and h2E1 for hOR. The results demonstrate the usefulness of the coexpression system for mechanistic studies and illustrate that the interaction of monooxygenase enzymes in the microsomal membrane is regulated by the presence of substrates and b5.
OBJECTIVE: To monitor the conduct of medical research projects that have already been approved by the local medical research ethics committee. DESIGN: Follow up study of ethically approved studies (randomly selected from all the studies approved in the previous year) by examination of patients' case notes, consent forms, and research records and by interview of the researchers at their workplace. SETTING: Tayside, Scotland (mixed rural and urban population). SUBJECTS: 30 research projects approved by Tayside local medical research ethics committee. MAIN OUTCOME MEASURES: Adherence to the agreed protocol, particularly for recruitment (obtaining and recording informed consent) and for specific requirements of the ethics committee, including notification of changes to the protocol and of adverse events. RESULTS: In one project only oral consent had been obtained, and in a quarter of the studies one or more consent forms were incorrectly completed. Inadequate filing of case notes in five studies and of consent forms in six made them unavailable for scrutiny. Adverse events were reported, but there was a general failure to report the abandoning or non-starting of projects in two studies the investigators failed to notify a change in the responsible researcher. CONCLUSIONS: Monitoring of medical research by local medical research ethics committees promotes and preserves ethical standards, protects subjects and researchers, discourages fraud, and has the support of investigators. We recommend that 10% of projects should undergo on-site review, with all others monitored by questionnaire. This would require about six person hours of time and a salary bill of 120 pounds per study monitored.
A significant restriction was demonstrated in the ability of herpes simplex virus type 1 virion host shutoff (vhs) mutant viruses to invade the corneal epithelium. Viral replication and invasion was confined to the areas of the cornea which were scarified prior to infection. Differences between wild-type and vhs mutant replication in corneas in vivo were 100- to 1000-fold at all timepoints postinfection. Smaller but still significant growth restrictions were observed in cultured corneal cells. This difference between in vitro and in vivo is not likely to be due to differences in cell cycle status since vhs-induced RNA degradation can occur in both cycling and noncycling cells in vitro. The vhs function is therefore important for invasion of the cornea and secondarily the nervous system and is thereby required for efficient establishment of latency.
A frequent cause of TGF-beta resistance is decreased expression or mutation of TGF-beta receptor Type II (TGFbetaRII) protein. We previously isolated two isogeneic subclones of the human bronchial epithelial cell line BEAS-2B that are respectively resistant (R.1) or sensitive (S.6) to the growth inhibitory effects of TGF-beta1. In this study, we examined TGFbetaIIR expression, ability to bind TGF-beta1, and cDNA sequence in the resistant cell line. Immunofluorescent analyses with antibody to TGFbetaRII indicated that this protein was expressed at the surface of R.1 cells. Affinity binding studies showed that TGF-beta1 bound equally well to the resistant (R.1) and sensitive (S.6) cell lines. PCR cloning and sequencing of TGFbetaRII cDNA revealed no changes from wild type in the resistant cell line. We conclude that alterations in TGF-beta Type II receptor are not responsible for TGF-beta resistance in this cell line.
Conversion by alpha-thrombin of the zymogen human protein C (HPC) to activated protein C (aPC) is an important physiologic feedback control mechanism for the coagulation cascade. Although activation of HPC by thrombomodulin-bound thrombin is relatively rapid, activation by free thrombin occurs at a significantly slower rate. Previously, we generated a "hyper-activatable" derivative of HPC (FLIN-Q3) with an increased activation rate by free alpha-thrombin in vitro. In this study, the antithrombotic efficacy of FLIN-Q3 was compared with both native zymogen and aPC in an arteriovenous shunt model of thrombosis in the guinea pig. Recombinant proteins were infused 15 minutes before and throughout a 15-minute period while blood was circulated from carotid to jugular through tubing that enclosed a thread on which fibrin was deposited. Parallel dose-dependent antithrombotic responses were observed. Under these non-steady-state conditions, the calculated infusion doses associated with a 50% reduction of thrombus mass were 2.7, 24, and 250 mg/kg/h for aPC, FLIN-Q3, and HPC, respectively. Thrombus weight correlated inversely with plasma concentration of aPC, measured amidolytically, from either direct infusion of aPC or that generated from the zymogens in the animal, and similarly correlated inversely with anticoagulant activity measured by whole blood aPTT. Neither zymogen form showed significant aPC activity before shunt circulation, suggesting a requirement for exposure to thrombin. After the infusion was discontinued for 15 minutes, a second period of thrombus formation in the shunt demonstrated the ability of zymogen forms of PC, unlike aPC, to provide "on-demand" anticoagulant responses to repeated thrombotic stimuli. Thus, a "hyper-activatable" PC molecule such as FLIN-Q3 may represent a superior form of anticoagulant therapy than either the native zymogen or aPC.
From an analysis of the distributions of measures of transmission rates among hosts, we identify an empirical relationship suggesting that, typically, 20% of the host population contributes at least 80% of the net transmission potential, as measured by the basic reproduction number, R0. This is an example of a statistical pattern known as the 20/80 rule. The rule applies to a variety of disease systems, including vector-borne parasites and sexually transmitted pathogens. The rule implies that control programs targeted at the "core" 20% group are potentially highly effective and, conversely, that programs that fail to reach all of this group will be much less effective than expected in reducing levels of infection in the population as a whole.
BACKGROUND: Osseointegrated implants allow patients with oromandibular defects to obtain complete or partial dentition via implant-assisted or implant-borne prostheses. Implants restore masticatory and occlusal function, improving oral intake and articulation. However, use of implants in head and neck cancer patients has been discouraged due to lack of data supporting their utility in these patients. This study attempts to establish the validity of using osseointegrated implants for dental restoration in head and neck cancer patients. METHODS: Six patients who underwent resection/reconstruction for head and neck cancer received osseointegrated implants. Integration was assessed clinically, radiographically, and mechanically at 4-8 months; oral intake, mastication, and articulation were evaluated 6-12 months after receiving the dental prosthesis. RESULTS: Osseointegration occurred in 92% (24/26) of the implants: 100% (14/14) in neomandibles and 83% (10/12) in native mandibles. One patient had implants (2/5) that failed to integrate. The remaining patients' implants were immobile, free of infection, with no osteoradionecrosis. These patients tolerated a regular diet and experienced weight gain and improved articulation. CONCLUSIONS: The advent of osseointegrated implants and their compatibility with native and neomandible allows the restoration of functional dentition in patients undergoing ablative surgery for head and neck cancer.