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Biomedical subjects

J M Carter

Publications and source records attributed to J M Carter.

At least 55 records · Page 3Linked to original sources
PubMed1996

Enforcement of drunken driving laws in cases involving injured intoxicated drivers.

STUDY OBJECTIVE: To determine the frequency of driving while impaired (DWI) charges among alcohol-intoxicated drivers injured in motor vehicle crashes (MVCs) and any differences in the group of those charged compared with those not charged. METHODS: We performed a retrospective analysis of linked data from medical and judicial sources. Our setting was an urban emergency department of a trauma center serving a population of 1 million. We studied consecutive drivers injured in MVCs over a period of 15 months who had measured serum ethanol (BAC) levels of 100 mg/dL or higher. BAC, Trauma Score (TS), demographics, and crash data were linked to court records of charges, outcome, and prior convictions. The group of individuals who were charged with DWI were compared with those who were not charged. RESULTS: One hundred eighty-seven patients were studied; 53 (28%) were charged with DWI, and 32 (17% of total) were convicted. Two (7%) of 29 patients with severe injuries, 9 (28%) of 32 with moderate injuries, and 42 (33%) of 126 with nonsevere injuries were charged (P = .004). Eighteen (16%) of 112 patients with no prior convictions were charged; 20 (56%) of 36 patients with one, 11 (52%) of 21 with two, 3 (25%) of 12 with three, and 0 of 5 with four or more prior DWI convictions were charged (P < .001). There were no significant differences in BAC, demographics, or other measures between the two groups. CONCLUSION: Alcohol-impaired drivers who require ED treatment for injuries sustained in an MVC are infrequently charged with DWI. The likelihood of a DWI charge diminishes with increasing severity of injury. Repeat offenders are charged more often, but the frequency of charges does not increase with increasing number of prior DWI convictions.

Accidents, Traffic↗
PubMed1996

Apparent idiopathic hyponatremia in an ambulatory geriatric population.

OBJECTIVES: The purpose of this descriptive analysis is to demonstrate that among older patients with hyponatremia, there is a subset with apparent hyponatremia of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) type, which appears associated with the aging process. A retrospective chart review was done to identify patients with hyponatremia and to classify them into non-SIADH, SIADH, and idiopathic categories. DESIGN: The participants were the ambulatory population of The Mount Sinai Hospital's outpatient geriatric clinic. Pertinent data generated during the antecedent 24 months were collected from outpatient charts and included sets of laboratory values (consisting of one sodium, glucose, BUN and creatinine level), age, sex, race, clinical history, present diagnosis, medications, and prescribed diets for each patient in the total population. RESULTS: Patients demonstrating hyponatremia with serum sodium levels of less than 135 mEq/L were identified from the total population and were further divided into SIADH and non-SIADH etiologies. The SIADH patients were then subdivided into known etiology SIADH and apparent idiopathic SIADH. In an ambulatory geriatric population of 405 subjects, 46 had hyponatremia, with SIADH the apparent cause in 27. Of the SIADH population, seven patients were considered to have idiopathic SIADH. An apparent predilection for development of this syndrome was observed among non-black patients and the old old. CONCLUSIONS: The results support the hypothesis that aging is a risk factor for the development of SIADH-like hyponatremia in a subset of older patients who do not have an apparent underlying etiology. Thus, aging may be an independent etiology for the development of hyponatremia.

Age Distribution↗
PubMed1996

The intermediate filament cytoskeleton of the lens: an ever changing network through development and differentiation. A minireview.

In the eye lens, intermediate filament proteins form two morphologically distinct polymers, 10-nm intermediate-sized filaments and beaded filaments. Coincidently, the beaded filament polymer and the proteins filensin and CP49 are specific to lens fibre cells and are therefore excellent markers for fibre cell differentiation. In the adult lens, filensin and CP49 are maintained throughout all stages of lens fibre cell differentiation whilst vimentin is apparently lost at a specific stage from the deeper cortical fibres. The expression of CP49 and filensin is coincident with the presence of beaded filaments suggesting these proteins are filament components. In association with alpha-crystallin, CP49 and filensin form beaded filaments in vitro. During fibre cell differentiation, filensin and CP49 are post-translationally modified. In the case of filensin, proteolysis results in two functionally distinct fragment sets, one derived from the alpha-helical rod domain and the other from the C-terminal tail domain of filensin. It is proposed that both filensin and CP49 are critically involved in organising the cytoplasmic and plasma membrane domains of the fibre cell and therefore essential to the optical properties of the lens.

Animals↗
PubMed1996

Alpha-quartz-induced chemokine expression by rat lung epithelial cells: effects of in vivo and in vitro particle exposure.

Chemokines are chemotactic cytokines that can play a key role in leukocyte recruitment to sites of tissue injury or infection. Previous studies have demonstrated that exposure to alpha-quartz as well as other noxious particles increases chemokine gene expression in rat lung, although the cells responsible for chemokine expression and the mechanisms underlying this response have remained unclear. The present studies demonstrate that exposure of rats to alpha-quartz induced expression of mRNA for the chemokine macrophage-inflammatory protein (MIP)-2 in epithelial cells lining the terminal bronchioles and alveolar ducts as well as macrophages and alveolar type II cells in the more distal lung. Treatment of rats with an anti-MIP-2 antiserum before alpha-quartz exposure markedly attenuated neutrophilic infiltration of the lungs demonstrating an important role for MIP-2 in alpha-quartz-induced pulmonary inflammation. In vitro exposure of primary cultures of rat alveolar type II cells or the rat alveolar type II cell line RLE-6TN to tumor necrosis factor-alpha, endotoxin, or alpha-quartz increased mRNA for MIP-2 as well as the structurally and functionally similar chemokine cytokine-induced neutrophil chemoattractant but not the chemokine MIP-1 alpha. The alpha-quartz-induced increase in epithelial MIP-2 mRNA resulted, at least in part, from increased gene transcription and was associated with the release of active MIP-2 protein. Induction of RLE-6TN MIP-2 and cytokine-induced neutrophil chemoattractant mRNA expression was not unique to alpha-quartz, being also increased by crocidolite asbestus fibers but not by titanium dioxide or MMVF-10 glass fibers. These findings indicate that epithelial cells contribute to chemokine expression in rat lung after exposure to alpha-quartz and potentially other noxious particles and suggest that alpha-quartz-activated MIP-2 expression in vivo results, at least in part, from a direct action of the particles on the lung epithelium.

Animals↗
PubMed1995

Characterization of phage that bind plastic from phage-displayed random peptide libraries.

During routine screenings of random peptide libraries displayed at the N terminus of the pIII coat protein of M13 bacteriophage, clones were isolated that bound directly to the polystyrene (PS) surface used to immobilize the target protein. The plastic-binding phage (P-b phi) bind to both unblocked plastic (PS and polyvinyl chloride, PVC) and plastic blocked with bovine serum albumin (BSA) but require non-ionic detergent to bind to plastic blocked with milk. Comparison of the P-b phi to antibody-binding phage (Ab-b phi) indicates that similar numbers of phage particles are bound, but fewer P-b phi the recovered by acid elution. Sequence determination of the displayed peptides reveals they lack amino-acid sequence similarity yet are highly enriched for the Tyr and Trp residues. However, because not all phage that display peptides rich in Tyr and Trp residues bind to plastic, and other methods of screening random peptide libraries have identified different classes of plastic-binding peptides, the relative abundance of Tyr and Trp residues should not be considered diagnostic of plastic-binding. In summary, these results help characterize one of the most common methods used to screen random peptide libraries and suggest strategies to avoid isolating P-b phi. Furthermore, while it is generally believed that proteins bind to plastic by non-specific interactions, these results show that a bias in aa composition can exist.

Amino Acid Sequence↗
PubMed1995

Cloning, expression, and functional characterization of rat MIP-2: a neutrophil chemoattractant and epithelial cell mitogen.

Macrophage inflammatory protein-2 (MIP-2) is a member of a family of cytokines that play roles in inflammatory, immune, and wound healing responses. To clone the cDNA for rat MIP-2, RNA was isolated from the lungs of Fischer 344 rats after instillation of lipopolysaccharide. Reverse transcription-polymerase chain reaction was performed by using synthetic oligonucleotide primers designed from the mouse MIP-2 cDNA sequence. A cDNA containing the coding region of rat MIP-2 was cloned and sequenced. Comparison to the mouse MIP-2 cDNA demonstrated 90.3% homology at the nucleotide level and 86% homology at the amino acid level. The rat MIP-2 cDNA was expressed in Escherichia coli and protein evaluated for bioactivity. The recombinant rat MIP-2 was chemotactic for rat neutrophils but did not stimulate migration of rat alveolar macrophages or human peripheral blood eosinophils or lymphocytes. In addition, the recombinant rat MIP-2 and the related rat chemokine, KC/CINC stimulated proliferation of rat alveolar epithelial cells but not fibroblasts in vitro.

Amino Acid Sequence↗
PubMed1995

TNF alpha and increased chemokine expression in rat lung after particle exposure.

Macrophage inflammatory protein 2 (MIP-2) and CINC (Cytokine-Induced-Neutrophil-Chemoattractant) are members of the chemokine family of inflammatory and immunoregulatory cytokines. MIP-2 and CINC exhibit potent neutrophil chemotactic activity and are thought to be key mediators of inflammatory cell recruitment in response to tissue injury and infection. In the present studies, we examined the potential involvement of MIP-2 and CINC in particle-elicited inflammation in the rat lung and the role of TNF alpha in particle-induced chemokine expression. Acute intratracheal instillation exposure of F344 rats to alpha quartz or titanium dioxide was shown to markedly increase steady-state levels of MIP-2 and CINC mRNA in lung tissue; a response which was associated with a significant increase in neutrophils in the bronchoalveolar lavage fluid. Additional studies demonstrated that acute inhalation of crocidolite fibers by rats also induced increased MIP-2 and CINC expression. Since previous studies had demonstrated that TNF alpha stimulates MIP-2 and CINC expression in vitro and that particle exposure induces TNF alpha production in rat lung we examined the role of TNF alpha in alpha quartz-induced MIP-2 gene expression. We demonstrated that passive immunization of mice against TNF alpha markedly attenuated the increased lung MIP-2 mRNA seen in response to alpha quartz inhalation. Collectively, these findings suggest that the chemokines MIP-2 and CINC play a role in neutrophil recruitment to the rat lung after particle exposure and indicate that particle-induced expression of these chemokines is mediated, at least in part, by production of TNF alpha.

Animals↗
PubMed1995

In vitro studies on the assembly properties of the lens proteins CP49, CP115: coassembly with alpha-crystallin but not with vimentin.

A rapid one-step purification procedure for CP49, an intermediate filament protein found in the lens, is described using reverse-phase HPLC. This protein is one of the major intermediate filament proteins of the lens fibre cells and is found in both the water insoluble fraction (WIF) and the water soluble fraction (WSF) of the lens. In order to better understand the physiological role of CP49 in lens transparency we have purified CP49 from both compartments and compared the in vitro assembly characteristics of both by electron microscopy and sedimentation assays. Our studies showed that CP49, when mixed with another lens intermediate filament protein, CP115, forms 10 nm intermediate filaments. Vimentin, another intermediate filament protein found in the lens, was unable to coassemble with CP115, thus demonstrating the specificity of the interaction of CP49 with CP115. CP49 isolated from either the WIF or the WSF formed 10-nm filaments with CP115 and indicated that CP49 from both these lens cell compartments had similar in vitro assembly characteristics. This also suggested that the post-translational modifications observed for CP49 from the different compartments was of little apparent consequence to filament formation. The inability to reconstitute beaded filaments from CP49 and CP115 suggested that other lens proteins may be needed in the reconstitution assay before these lens specific cytoskeletal elements could be repolymerised from their purified protein components. CP49 and CP115 were therefore assembled in the presence of alpha-crystallins and a beaded filament structure was observed as has been seen with type III intermediate filament proteins assembled with alpha-crystallins.

Animals↗
PubMed1995

Vimentin and CP49/filensin form distinct networks in the lens which are independently modulated during lens fibre cell differentiation.

The cells of the eye lens contain the type III intermediate filament protein vimentin, as well as two other intermediate filament proteins, CP49 and filensin. These two proteins appear to be unique to the differentiated lens fibre cell. Immunoblotting and confocal microscopy were used to describe changes which occur in these three intermediate filament proteins and the networks they form during fibre cell differentiation and maturation. The vimentin network was present in both epithelial cells and some fibre cells. Fibre cells were vimentin positive up to a specific point 2-3 mm in from the lens capsule where the vimentin signal was drastically reduced. The CP49/filensin network was not present in the undifferentiated epithelial cells but emerged in the differentiating fibre cells. This latter network exhibited a principally plasma membrane localization in younger fibre cells but became more cytoplasmic in older fibre cells. This change also occurred at a distinct point in fibre cell differentiation, much earlier than the observed loss of the vimentin network. The subcellular changes in the distributions of these cytoskeletal networks were correlated to the loss of the fibre cell nucleus, another feature of fibre cell differentiation. No correlation was found to changes in the vimentin network but nuclear loss did coincide with changes in the CP49/filensin network. Concomitant with nuclear pyknosis, there were also changes in the nuclear lamina as well as infringement of the nuclear compartment by CP49, as shown by confocal microscopy. This study demonstrates vimentin and the CP49/filensin network to be independent in the lens but both networks undergo dramatic changes in subcellular distribution during the differentiation/maturation of the fibre cell. Only changes in the CP49/filensin network can be correlated to nuclear loss. Thus in the lens, unlike mammalian erythropoiesis which is also characterized by nuclear loss, the vimentin network does not appear linked to nuclear retention.

Animals↗
PubMed1995

Distribution of putative D4 dopamine receptors in postmortem striatum from patients with schizophrenia.

The identification of five dopamine receptor subtypes has given the dopamine hypothesis of schizophrenia new life. The D4 receptor is particularly intriguing because it binds clozapine with high affinity. Putative D4 receptors were labeled in postmortem human brain by subtracting the binding of a saturating concentration of 3H-raclopride (6 nM, which labels D2 and D3 receptors) from that labeled by a saturating concentration of [3H]YM 09151-2 (1-1.3 nM, which labels D2, D3, and D4 receptors). In the control brain, putative D4 receptors show a homogenous distribution in striatum and nucleus accumbens. This is also true in schizophrenic brains, although the levels are significantly higher (twofold). These data are inconsistent with mRNA studies that have shown negligible amounts in striatum and accumbens, with modest amounts reported in most of cerebral cortex. These findings suggest that the putative D4 receptors are not synthesized in this region, but are presynaptically localized on striatal afferent terminals. Our findings confirm and extend the report of Seeman et al. (1993). Extension of these findings into the nucleus accumbens is important because of its extensive connections to the limbic system while the putamen is exclusively "motor" striatum.

Adult↗
PubMed1994

Quantitative autoradiography of dopamine-D1 receptors, D2 receptors, and dopamine uptake sites in postmortem striatal specimens from schizophrenic patients.

A number of previously published homogenate receptor binding studies have postulated that dopaminergic dysfunction in schizophrenia may be related to abnormalities in dopamine receptors. In this study, postmortem striatal specimens from patients with schizophrenia, normal controls, and psychiatric controls that had received neuroleptics were studied with quantitative autoradiography for dopamine receptors. Autoradiography with single concentrations of [3H]-SCH 23390 for D1 receptors, [3H]-raclopride for D2 receptors, and [3H]-CFT for dopamine uptake sites failed to define significant differences between the study groups. [3H]-CFT bound in a patchy distribution in the striatum that is believed to correspond to striosomal and matrix striatal compartments. There were no differences between groups when [3H]-CFT binding density was examined in the striosomal and matrix compartments. There were also no differences between groups in the percentage of striatal area occupied by striosomal or matrix compartments as defined by [3H]-CFT binding. We conclude that abnormalities of these dopamine receptor subtypes are probably not primary features of the schizophrenic syndrome in the brain collection examined. Previous reports of elevated D2 receptor binding in schizophrenia may have been related to drug treatment effects. Alternatively, the relatively high affinity of ligands used in previous studies for D4 receptors may explain the discrepancy in our findings. Unchanged [3H]-CFT binding in the schizophrenic group also suggests that the density of mesostriatal neuronal terminals is not altered in schizophrenia.

Autoradiography↗
PubMed1994

Hepatitis C seroprevalence in bone marrow transplant recipients and haemophiliacs.

AIM: To determine the prevalence of antibodies to hepatitis C (anti-HCV) in patients who have undergone bone marrow transplantation in Wellington, prior to the introduction of hepatitis C screening, and to contrast these results with the prevalence of anti-HCV in the Wellington haemophiliac population. METHOD: Serum specimens were obtained from 30 patients who had undergone bone marrow transplantation for the treatment of haematological disorders, and from 29 haemophiliacs. Specimens were analysed using a second generation HCV immunoassay. RESULTS: Exposure to blood products was high in bone marrow transplant recipients with subjects receiving red cells or platelets from an average of 53 donors (range 15-100, SD 23.2) during their transplant procedure. Despite the high usage of blood products, only one of the 30 patients tested was positive for hepatitis C on the basis of second-generation antibody testing. Confirmatory testing in this patient, (anti-HCV immunoblot assay) was negative. In contrast, 26 of 29 (89%) haemophiliac patients tested were positive for anti-HCV. CONCLUSION: Although the infective risk of blood products cannot be underestimated, the risk of patients contracting hepatitis C from multiple single-unit transfusions, prior to the introduction of screening for hepatitis C was low. This contrasts with the high risk of hepatitis C seroconversion in patients exposed to pooled plasma products.

Adolescent↗
PubMed1994

Plasmodium falciparum: further characterization of a functionally active region of the merozoite invasion ligand EBA-175.

A 42 amino acid peptide, Pf EBA-175 (1062-1103), also called EBA-peptide 4 of the 175-kDa Plasmodium falciparum sialic acid binding protein, a putative merozoite invasion ligand, has been shown to be a target of parasite growth inhibitory antibodies. We expressed and purified a recombinant protein, NS1-Pf EBA-175 (946-1133) which included the 42 amino acid peptide, and compared antibodies induced by immunization with the protein to antibodies raised against the 42 amino acid peptide. Sera from rabbits immunized with the recombinant protein and the synthetic peptide immunoprecipitated authentic EBA-175, and had comparable ELISA titers against peptide Pf EBA-175 (1062-1103). However, IFAT titers against infected erythrocytes and growth inhibitory activity were substantially higher in sera from animals immunized with the 42 amino acid synthetic peptide. Epitope mapping of the 42 amino acid peptide identified a 19 amino acid peptide, Pf EBA-175 (1069-1087), which blocked the ability of antibodies against the 42 amino acid peptide to (1) immunoprecipitate EBA-175, (2) bind to the 42 amino acid peptide in an ELISA, and (3) recognize infected parasites in an IFAT. Sera from rabbits immunized with the 19 amino acid peptide conjugated to KLH had excellent parasite growth inhibitory activity (at 1:5 serum dilution, 49.9 +/- 7.4%, mean +/- SD of three separate assays), but the activity was lower in each of the three assays than that of sera from rabbits immunized with the 42 amino acid peptide (67.8 +/- 24.8%). These data indicate that the activity of antibodies raised against the linear 42 amino acid peptide, Pf EBA-175 (1062-1103) are primarily, if not exclusively, directed against 19 of the 42 amino acids, and identify this region of Pf EBA 175 as a target for vaccine development.

Amino Acid Sequence↗
PubMed1994

Can mandatory pretransfusion approval programmes be improved?

To improve the appropriateness of blood-component prescribing, a mandatory haematologist pretransfusion approval programme of all non-red-cell components was instituted. This was associated with a 33% decrease in the units of fresh frozen plama (FFP) transfused. Platelet transfusions increased but utilization of both platelets and FFP are now the lowest of the six comparable blood transfusion regions in New Zealand. A subsequent concurrent audit, using preset criteria, of FFP, cryoprecipitate and platelet usage over a 3-month period showed that further reductions in blood component usage could still be achieved, despite the continuing pretransfusion approval policy. This audit showed that 33% of FFP and 30% of cryoprecipitate units transfused were inappropriately given, despite prior haematologist approval. Hospital transfusion practices can be improved by mandatory blood-component pretransfusion approval but concurrent auditing of this programme is required to identify and correct continuing inappropriate blood-component prescribing. Haematologists need to agree on blood-component indications prior to instituting a pretransfusion approval programme in order to provide optimal management.

Blood Banks↗
PubMed1994

Increase in haematocrit in borderline hypertensive men.

1. Haematologic parameters were measured in untreated borderline hypertensive (BHT) men, and weight and age matched with normotensive men to determine whether previously described increased haematocrit (Hct) in established hypertension is evident in borderline hypertension. 2. Haematocrit was significantly increased in BHT men (mean 0.46, s.d. 0.032) compared with normotensive men (mean 0.43, s.d. 0.014) and correlated significantly with mean arterial pressure in this group (r = 0.67, P = 0.036) independent of weight. 3. The correlation of blood pressure with Hct in BHT men supports the concept that increased Hct may contribute to increased blood viscosity and thus to raised arterial pressure.

Adult↗