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R Curtis

Publications and source records attributed to R Curtis.

At least 19 recordsLinked to original sources
PubMed1998

Axotomy upregulates the anterograde transport and expression of brain-derived neurotrophic factor by sensory neurons.

In addition to the known retrograde transport of neurotrophins, it is now evident that endogenous brain-derived neurotrophic factor (BDNF) is transported in the anterograde direction in peripheral and central neurons. We used a double-ligation procedure that distinguishes between anterograde and retrograde flow to quantify the anterograde transport of endogenous neurotrophins and neuropeptides in the peripheral nervous system before and after axotomy. BDNF accumulation proximal to the ligation (anterograde transport) was twice that distal to the ligation (retrograde direction). Anterograde transport of nerve growth factor and neurotrophin-3 was not evident. Furthermore, BDNF anterograde transport increased 3.5-fold within 24 hr after sciatic nerve injury or dorsal rhizotomy. Anterograde transport of substance P and calcitonin gene-related peptide decreased after peripheral nerve lesion, demonstrating that there was no generalized increase in anterograde transport. To determine the source of the anterogradely transported BDNF, we performed in situ hybridization in a variety of tissues before and after axotomy. Expression of BDNF mRNA in proximal nerve segments did not change with treatment, showing that the increased accumulation of BDNF was not a result of increased local synthesis. BDNF mRNA and protein were expressed by dorsal root ganglion sensory neurons but not by motor neurons. BDNF mRNA expression was increased 1 d after nerve injury, and BDNF protein was also increased twofold to threefold, suggesting that sensory neurons are the major contributing source of the increased BDNF traffic in the sciatic nerve. Our results suggest that increased anterogradely transported BDNF plays a role in the early neuronal response to peripheral nerve injury at sites distal to the cell body.

Animals↗
PubMed1998

A splice variant of trkB and brain-derived neurotrophic factor are co-expressed in retinal pigmented epithelial cells and promote differentiated characteristics.

There is evidence suggesting reciprocal trophic interactions between photoreceptors and the retinal pigmented epithelium (RPE), but the factors involved have not been identified. In this study, we investigated the hypothesis that one or more known neurotrophic factors act upon the RPE. Cultured human and freshly isolated bovine RPE cells demonstrated saturable specific binding for [125I]labeled BDNF, NT-4/5 and NT-3 with little specific binding for CNTF and none for NGF. Cross-competition experiments showed that BDNF is the preferred ligand and cross-linking of [125I]BDNF resulted in a doublet at 160 kd that was increased in RPE cells incubated in all-trans retinoic acid. There was basal phosphorylation of a 145 kd protein recognized by an anti-trk antibody that was increased in RPE cells pulsed with BDNF. RT-PCR with primers spanning the transmembrane domain demonstrated that RPE cells express trkB mRNA lacking a region homologous to exon 9 of chicken trkB, a splice variant that has been demonstrated to preferentially interact with BDNF. Northern blots demonstrated that cultured RPE cells also express mRNA for BDNF. BDNF did not stimulate proliferation or increase survival of RPE cells in serum-free medium, but promoted a differentiated morphology and increased the expression of cellular retinaldehyde binding protein, a marker of the differentiated state in RPE cells. An RPE cell line that spontaneously shows differentiated features showed a high level of BDNF mRNA. These data demonstrate that RPE cells express a short splice variant of trkB whose activation correlates with expression of differentiated characteristics and the cells themselves are capable of producing a ligand for the receptors. Signaling through trkB could play a role in differentiation of RPE cells during development and maintenance of the differentiated state in adult RPE.

Animals↗
PubMed1998

Axonal transport of neurotrophins by visceral afferent and efferent neurons of the vagus nerve of the rat.

The receptor-mediated axonal transport of [125I]-labeled neurotrophins by afferent and efferent neurons of the vagus nerve was determined to predict the responsiveness of these neurons to neurotrophins in vivo. [125I]-labeled neurotrophins were administered to the proximal stump of the transected cervical vagus nerve of adult rats. Vagal afferent neurons retrogradely transported [125I]neurotrophin-3 (NT-3), [125I]nerve growth factor (NGF), and [125I]neurotrophin-4 (NT-4) to perikarya in the ipsilateral nodose ganglion, and transganglionically transported [125I]NT-3, [125I]NGF, and [125I]NT-4 to the central terminal field, the nucleus tractus solitarius (NTS). Vagal afferent neurons showed minimal accumulation of [125I]brain-derived neurotrophic factor (BDNF). In contrast, efferent (parasympathetic and motor) neurons located in the dorsal motor nucleus of the vagus and nucleus ambiguus retrogradely transported [125I]BDNF, [125I]NT-3, and [125I]NT-4, but not [125I]NGF. The receptor specificity of neurotrophin transport was examined by applying [125I]-labeled neurotrophins with an excess of unlabeled neurotrophins. The retrograde transport of [125I]NT-3 to the nodose ganglion was reduced by NT-3 and by NGF, and the transport of [125I]NGF was reduced only by NGF, whereas the transport of [125I]NT-4 was significantly reduced by each of the neurotrophins. The competition profiles for the transport of NT-3 and NGF are consistent with the presence of TrkA and TrkC and the absence of TrkB in the nodose ganglion, whereas the profile for NT-4 suggests a p75 receptor-mediated transport mechanism. The transport profiles of neurotrophins by efferent vagal neurons in the dorsal motor nucleus of the vagus and nucleus ambiguus are consistent with the presence of TrkB and TrkC, but not TrkA, in these nuclei. These observations describe the unique receptor-mediated axonal transport of neurotrophins in adult vagal afferent and efferent neurons and thus serve as a template to discern the role of specific neurotrophins in the functions of these visceral sensory and motor neurons in vivo.

Animals↗
PubMed1998

Prothrombotic disorders in infants and children with cerebral thromboembolism.

BACKGROUND: To our knowledge, the contribution of prothrombotic conditions to cerebral thromboembolism has never been prospectively studied in a large series of pediatric patients. METHODS: The Hospital for Sick Children, Toronto, Ontario, established a program in January 1992 to diagnose and treat children (term newborn to 18 years old) with arterial ischemic stroke or sinovenous thrombosis. The routine evaluation for prothrombotic conditions included plasminogen, antithrombin, protein C, free protein S, activated protein C resistance, IgG and IgM anticardiolipin antibody, and lupus anticoagulant. We analyzed samples taken within 2 years of the event. We report results on patients seen from January 1, 1992, to January 1, 1997. RESULTS: Ninety-two patients (47 males and 45 females) entered the program during the study interval. Patients ranged from newborn to 18 years in age. Arterial ischemic stroke occurred in 78% of patients while sinovenous thrombosis occurred in 22%. All were tested for prothrombotic disorders. One or more abnormal results were present in 35 (38%) of the 92 patients. The majority (21/35) had multiple abnormal test results. The abnormal test results were anticardiolipin antibody (33%), plasminogen (9.5%), activated protein C resistance (9%), protein C (7%), antithrombin (12.5%), lupus anticoagulant (8%), and free protein S (11.5%). Male sex predicted the presence of prothrombotic abnormalities (relative risk, 1.7; 95% confidence interval, 1.2-2.5), but stroke type (relative risk, 0.8; 95% confidence interval, 0.7-1.1), age group, and presence of other risk factors did not predict abnormal testing. CONCLUSIONS: A significant proportion (38%) of children with cerebral thromboembolism had evidence of prothrombotic conditions. In particular, there was a predominance of children with anticardiolipin antibody (33%). These data support a recommendation that children with cerebral thromboembolism be evaluated for prothrombotic disorders.

Adolescent↗
PubMed1998

Neuronal injury increases retrograde axonal transport of the neurotrophins to spinal sensory neurons and motor neurons via multiple receptor mechanisms.

We investigated the retrograde axonal transport of 125I-labeled neurotrophins (NGF, BDNF, NT-3, and NT-4) from the sciatic nerve to dorsal root ganglion (DRG) sensory neurons and spinal motor neurons in normal rats or after neuronal injury. DRG neurons showed increased transport of all neurotrophins following crush injury to the sciatic nerve. This was maximal 1 day after sciatic nerve crush and returned to control levels after 7 days. 125I-BDNF transport from sciatic nerve was elevated with injection either proximal to the lesion or directly into the crush site and after transection of the dorsal roots. All neurotrophin transport was receptor-mediated and consistent with neurotrophin binding to the low-affinity neurotrophin receptor (LNR) or Trk receptors. However, transport of 125I-labeled wheat germ agglutinin also increased 1 day after sciatic nerve crush, showing that increased uptake and transport is a generalized response to injury in DRG sensory neurons. Spinal cord motor neurons also showed increased neurotrophin transport following sciatic nerve injury, although this was maximal after 3 days. The transport of 125I-NGF depended on the expression of LNR by injured motor neurons, as demonstrated by competition experiments with unlabeled neurotrophins. The absence of TrkA in normal motor neurons or after axotomy was confirmed by immunostaining and in situ hybridization. Thus, increased transport of neurotrophic factors after neuronal injury is due to multiple receptor-mediated mechanisms including general increases in axonal transport capacity.

Animals↗
PubMed1998

Drug scene roles and HIV risk.

AIMS: Drug scenes (social and spatial drug-using and drug-selling environments) have complex role structures. Many drug injectors earn money or drugs as drug or syringe sellers, hit doctors (people who help others to inject) commercial sex workers, or in other roles. This paper aims to measure "role behaviors" of drug injectors; describe which drug injectors are more likely to engage in such role behaviors; and to determine whether roles are related to elements of HIV risk. DESIGN: Cross-sectional study of drug injectors. SETTING: Bushwick, a section of Brooklyn, New York, a major location for injection drug use and drug sales. PARTICIPANTS: Seven hundred and sixty-seven street-recruited drug injectors. MEASUREMENTS: Participants were interviewed about their roles, behaviors, socio-demographics and risk networks; sera were collected and assayed for HIV and hepatitis B core antibody. FINDINGS: Socio-demographic variables are related to role-holding in complex ways. Economic need is generally associated with engaging in drug-scene role behaviors. Holders of these roles are at greater behavioral and network risk for HIV and other blood-borne infections than are other drug injectors. They also engage in extensive communication with other drug users, including discussion of HIV risk reduction. CONCLUSION: Role behaviors can be measured in quantitative studies, and seem to be related to HIV risk. Role-holders may be strategic targets for risk-reduction campaigns. It seems feasible and advisable to measure drug scene role-holding in research on drug users.

Adult↗
PubMed1997

Effect of in vivo and in vitro degradation on molecular and mechanical properties of various low-molecular-weight polylactides.

The in vivo and in vitro degradation of low-molecular-weight poly(L-lactide), poly(L/D-lactide), and poly (L/DL-lactide) rods was investigated. The low-molecular-weight fast-degrading materials were used to accelerate the degradation process and make the test conditions more critical. In the in vivo study the rods were implanted in the soft tissue of sheep and explanted at 1, 3, 6, and 12 months. In the in vitro experiments the samples were subjected to aging at 37 degrees C in the phosphate buffer using two different modes. In the so-called pseudodynamic mode the aging buffer was regularly replaced if the pH dropped more than 0.5. In the static mode the buffer was not changed over the whole testing period of 52 weeks. The mechanical, molecular, and crystalline properties of the rods were measured and their appearance in the course of aging was evaluated using scanning electron microscopy. It was found that the changes in the mechanical properties of poly(L-lactide), poly(L/D-lactide), and poly(L/DL-lactide) samples subjected to in vitro degradation tests in both the static and pseudodynamic modes are in good approximation with data obtained from the in vivo study. The pH of the buffer solution had no evident effect on the mechanical properties or the rate of degradation as estimated from the drop in molecular weight of the aged samples. The replacement of the aging buffer to maintain a constant pH at 7.4 does not seem to be critical for the degradation of the polylactides. In vitro degradation tests can be used as a relevant procedure for predicting the in vivo functionality of implants from the polylactides used if the criteria for assessing such a functionality are the changes in mechanical properties and molecular weight.

Animals↗
PubMed1997

Neurotrophin-3 administration attenuates deficits of pyridoxine-induced large-fiber sensory neuropathy.

Chronic treatment of adult rats for 2-3 weeks with high doses of pyridoxine (vitamin B6) produced a profound proprioceptive loss, similar to that found in humans overdosed with this vitamin or treated with the chemotherapeutic agent cisplatin. Pyridoxine toxicity was manifest as deficits in simple and precise locomotion and sensory nerve function and as degeneration of large-diameter/large-fiber spinal sensory neurons. As assessed quantitatively in a beam-walking task and by EMG recording of H waves evoked by peripheral nerve stimulation, coadministration of the neurotrophic factor neurotrophin-3 (NT-3; 5-20 mg . kg-1 . d-1, s.c.) during chronic pyridoxine treatment largely attenuated the behavioral and electrophysiological sequelae associated with pyridoxine toxicity. Furthermore, NT-3 administration prevented degeneration of sensory fibers in the dorsal column of the spinal cord. These data are consistent with the evidence that NT-3 is a target-derived neurotrophic factor for muscle sensory afferents and suggest that pharmacological doses of NT-3 may be beneficial in the treatment of large-fiber sensory neuropathies.

Animals↗
PubMed1997

Sex, drugs, and infections among youth. Parenterally and sexually transmitted diseases in a high-risk neighborhood.

BACKGROUND AND OBJECTIVES: To determine the extent to which youth who reside in households in a neighborhood with large numbers of drug injectors 1) are infected with parenterally or sexually transmitted agents, and 2) engage in high-risk behaviors. STUDY DESIGN: A multistage probability household sample survey was conducted in Bushwick, Brooklyn from 1994 to 1995. All households in 12 randomly selected primary sampling units were screened for age-eligible youth. One hundred eleven English-speaking 18- to 21-year-olds were interviewed. One hundred three sera were tested for human immunodeficiency virus type 1 (HIV-1), Hepatitis B virus, hepatitis C virus (HCV), human T-cell lymphotrophic virus types I and II (HTLV-I/II), herpes simplex virus type 2 (HSV-2), or syphilis. Urines were tested for chlamydial infection, and for opiate and cocaine metabolites. RESULTS: Eighty-nine percent had sex in the past year, 45% with two or more partners. Only 19% of the sexually active always used condoms. Two (of 95) had had sex with a crack smoker. Thirty percent of women reported being coerced the first time they had sex, and 23% of women and 3% of men reported having been sexually abused. Only 3% reported ever using heroin, and 9% cocaine. Only one reported ever having injected drugs or smoked crack. Some underreporting of stigmatized behaviors occurred: two "nonreporters" had opiate-positive urines and two had cocaine-positive urines. Marijuana use was common, with 48% using it in the past year. No subjects tested positive for HIV-1, HIV-II, or syphilis; 2% tested positive for HTLV-I and 3% for hepatitis C; 3% had hepatitis B markers, 12% had chlamydial infection, and 50% serologic HSV-2 markers. CONCLUSIONS: Population-representative samples of high-risk communities can provide important knowledge. Although heroin and cocaine use, during drug injection, and rates of infection with parenterally transmitted infectious agents appear to be lower among these youth, sexual risk behaviors and chlamydial and HSV-2 infection are widespread. Sexually transmitted disease screening and outreach strategies are needed both to prevent sexually transmitted disease sequelae (including potential increased susceptibility to HIV infection) and to prevent transmission to partners.

Adolescent↗
PubMed1997

Sociometric risk networks and risk for HIV infection.

OBJECTIVES: This study examined whether networks of drug-injecting and sexual relationships among drug injectors are associated with individual human immunodeficiency virus (HIV) serostatus and with behavioral likelihood of future infection. METHODS: A cross-sectional survey of 767 drug injectors in New York City was performed with chain-referral and linking procedures to measure large-scale (sociometric) risk networks. Graph-theoretic algebraic techniques were used to detect 92 connected components (drug injectors linked to each other directly or through others) and a 105-member 2-core within a large connected component of 230 members. RESULTS: Drug injectors in the 2-core of the large component were more likely than others to be infected with HIV. Seronegative 2-core members engaged in a wide range of high-risk behaviors, including engaging in risk behaviors with infected drug injectors. CONCLUSIONS: Sociometric risk networks seem to be pathways along which HIV travels in drug-injecting peer groups. The cores of large components can be centers of high-risk behaviors and can become pockets of HIV infection. Preventing HIV from reaching the cores of large components may be crucial in preventing widespread HIV epidemics.

Adult↗
PubMed1996

High-risk personal networks and syringe sharing as risk factors for HIV infection among new drug injectors.

In a cross-sectional study of 174 new injecting drug users (IDUs) in New York City who had injected for < or = 6 years, we examined whether those who both share syringes and have personal risk networks that include high-risk injectors are particularly likely to be infected with HIV. Subjects were street recruited between July 1991 and January 1993, were interviewed about their risk behaviors in the prior 2 years and their personal risk networks with other IDUs in the prior 30 days, and were tested for HIV; 20% were HIV seropositive. Among those who both shared syringes and had a personal risk network member who injected more than once a day, 40% were HIV seropositive (versus 14% for others, p < 0.001). In simultaneous multiple logistic regression, the interaction of both sharing syringes and having a personal risk network member who injected more than once a day remained independently and significantly associated with being HIV seropositive (OR, 3.57; 95% CI, 1.22, 10.43; p < 0.020), along with Latino race/ethnicity and exchanging sex for money or drugs. These findings suggest that the combination of sharing syringes with having a high-risk personal network is a risk factor for HIV infection among new IDUs. Studies of risk factors for HIV infection among new IDUs and interventions to reduce the spread of HIV among them should focus on their risk networks as well as their risk behaviors.

Adult↗
PubMed1996

Syringe-mediated drug sharing among injecting drug users: patterns, social context and implications for transmission of blood-borne pathogens.

Drug injectors are at risk for infection with human immunodeficiency virus (HIV) and other blood-borne pathogens through the exchange of (infected) blood resulting from unhygienic injecting practices. Research attention and public discussion have focused primarily on the sharing of syringes and needles. While the focus on syringe sharing has sparked important interventions (bleach distribution, syringe exchange) it may have obscured the social relationship in which injecting equipment is used. Drug sharing plays a crucial role in the social organization of the drug using subculture. In this paper, various drug sharing practices and other distinguishable aspects of the injecting process-collectively termed Syringe-Mediated Drug Sharing (SMDS)-are described. All of these behaviors may put injecting drug users (IDUs) at risk for infection. The purpose of this paper is to stimulate scientific inquiry into SMDS behaviors and the social contexts which shape them. Descriptions are based primarily on field studies in Rotterdam and New York City. Recommendations for safer injecting training and education are proposed, as are directions for future research.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Characterization of transmissible gastroenteritis coronavirus S protein expression products in avirulent S. typhimurium delta cya delta crp: persistence, stability and immune response in swine.

The spike protein from transmissible gastroenteritis virus (TGEV) was expressed in attenuated S. typhimurium delta cya delta crp delta asd chi 3987. Three partially overlapping fragments of TGEV S gene, encoding the amino-terminal, intermediate, and carboxy-terminal end of the protein, as well as the full length gene were inserted into the asd+ plasmid pYA292 to generate recombinant plasmids pYATS-1, pYATS-2, pYATS-3, and pYATS-4, respectively, which were transformed into S. typhimurium chi 3987. Recombinant S. typhimurium chi 3987 (pYATS-1) and chi 3987 (pYATS-4) expressing constitutively a 53 kDa amino-terminal fragment of the S protein and the full length protein (144 kDa), respectively, showed high stability. After 50 generations in vitro 60% and 20% of the bacteria transformed with pYATS-1 and pYATS-4, respectively, expressed the S-protein antigen. Since S. typhimurium chi 3987 (pYATS-1) showed a better level of expression and stability in vitro, this recombinant strain was selected as a potential bivalent vector to induce both immunity to Salmonella and TGEV in swine. In order to study colonization of swine tissues by S. typhimurium delta cya delta crp, a gene conferring resistance to rifampicin was cloned into the chromosome of S. typhimurium chi 3987, generating chi 4509 strain. Both S. typhimurium chi 4509 (pYA292) and chi 4509 (pYATS-1) colonized the ileum of orally inoculated swine with clearance of bacteria between days 10-20 post-infection. The expression of the amino-terminal fragment of the S protein diminished the ability of S. typhimurium chi 4509 (pYATS-1) to colonize deep tissues. The recombinant strain S. typhimurium chi 3987 (pYATS-1) induced TGEV specific antibodies in both serum and saliva of orally inoculated swine.

Animals↗
PubMed1996

Role of the acid tolerance response in virulence of Salmonella typhimurium.

During its life cycle, Salmonella typhimurium is exposed to a variety of acidic conditions. Survival in the acidic environments within the host may require the adaptive acid tolerance response (ATR), which is characterized by the induction of several Salmonella proteins upon exposure to mildly acidic conditions. These induced proteins protect the bacterium from death under severe acid challenge. The goal of this study was to examine the role of ATR in Salmonella pathogenesis. Initially, we observed that differences exist between the virulent S. typhimurium strains and the laboratory S. typhimurium strain LT2 with respect to their ATR. Mutations affecting the ATR of S. typhimurium LT2, including atrB, atrC (polA), atrD, atbR, and fur, were crossed into virulent Salmonella strains, and the resultant transductants were screened for virulence in mice and acid sensitivity. Surprisingly, with the exception of the fur mutation, none of the muatations had a major effect on acid resistance or virulence in the pathogenic strains. The fur mutants showed a 1-to 3-log increase in the 50% lethal dose; however, the magnitude of its effect was dependent on the strain background. Strains containing two or three different atr mutations were constructed, and these were also examined for acid sensitivity and virulence. The double and triple mutants that contained an atrC mutation no longer displayed an ATR. Those mutants which were more acid sensitive were also highly attenuated, suggesting a strong correlation between the ability to mount and ATR and virulence in S. typhimurium. Comparison of the ability of the various atr single, double, and triple mutants to survive within macrophages showed that strains containing an atrC mutation survived much less than the wild type in bone marrow-derived macrophages. No difference in survival within J774 macrophage like cells were detected.

Acids↗
PubMed1995

TGF-beta s and cAMP regulate GAP-43 expression in Schwann cells and reveal the association of this protein with the trans-Golgi network.

We have shown previously that growth-associated protein 43 (GAP-43) is expressed by rat Schwann cells and is restricted to non-myelin-forming Schwann cells in vivo. Here we examined the regulation of GAP-43 using agents that are known to control Schwann cell differentiation in vitro. GAP-43 protein and mRNA levels are decreased by forskolin and other agents that elevate intracellular cAMP (and promote expression of the myelinating Schwann cell phenotype). We also found that expression of GAP-43 protein but not mRNA is down-regulated by transforming growth factor betas (TGF-beta s). Moreover, TGF-beta treatment of Schwann cells results in cell clumping, process retraction and disappearance of GAP-43 from the plasma membrane, revealing that GAP-43 is associated with the Golgi apparatus. This association was confirmed by partial overlap of GAP-43 with the trans-Golgi network marker (23c) and the disruption of the Golgi with brefeldin A or monensin leading to altered GAP-43 distribution. Golgi-associated GAP-43 appeared to have the same molecular weight as the plasma membrane-associated GAP-43. Thus these results show that GAP-43 expression in Schwann cells is subject to regulation by both extracellular and intracellular signalling molecules and that Schwann cell GAP-43 is often associated with the Golgi apparatus.

Animals↗