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Biomedical subjects

R Curtis

Publications and source records attributed to R Curtis.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1995

Pan-neurotrophin 1: a genetically engineered neurotrophic factor displaying multiple specificities in peripheral neurons in vitro and in vivo.

Pan-neurotrophin 1 (PNT-1) is a synthetic trophic factor engineered by combining active domains of the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3) into an NT-3 backbone. This molecule was produced in transiently transfected COS cells or in baculovirus-infected insect cells transfected COS cells or in baculovirus-infected insect cells and subsequently purified to homogeneity. Saturation binding in embryonic spinal sensory neurons demonstrated a greater number of high-affinity binding sites for PNT-1 than for its parental molecule NT-3. PNT-1 was shown to efficiently block the chemical crosslinking of NGF, BDNF, and NT-3 to their cognate Trk receptors and to the low-affintiy NGF receptor expressed on neuronal and nonneuronal cells. PNT-1 stimulated survival and proliferation of MG87 fibroblasts expressing either TrkA, TrkB, or TrkC. PNT-1 also promoted survival of a greater number of embryonic dorsal root ganglion neurons than any of the other neurotrophins alone, and its effects were equivalent to a combination of NGF, BDNF, and NT-3. Analysis of receptor-specific neurotrophic activities demonstrated that PNT-1 efficiently rescued TrkA mRNA-containing sympathetic neurons and TrkB and TrkC mRNA-containing sensory neurons from the dorsal root and nodose ganglia. Finally, PNT-1 showed robust retrograde transport to DRG neurons in vivo after injection into the sciatic nerve. Radiolabeled PNT-1 accumulated in small-, medium-, and large-sized neurons. Coinjection with different unlabeled neurotrophins inhibited PNT-1 transport in distinct subpopulations of neurons of different sizes, suggesting that this molecule affects sensory neurons of different modalities. These results indicate that PNT-1 is a potent and multispecific neurotrophic factor that may be useful in the treatment of peripheral neurophathies and nerve damage.

Animals↗
PubMed1995

Differential role of the low affinity neurotrophin receptor (p75) in retrograde axonal transport of the neurotrophins.

The receptor mechanisms mediating the retrograde axonal transport of the neurotrophins have been investigated in adult rats. We show that transport of the TrkB ligands NT-4 and BDNF to peripheral neurons is dependent on the low affinity neurotrophin receptor (LNR). Pharmacological manipulation of LNR in vivo using either an anti-LNR antibody or a soluble recombinant LNR extracellular domain completely blocked retrograde transport of NT-4 and BDNF to sensory neurons, while having minimal effects on the transport of NGF in either sensory or sympathetic neurons. Furthermore, in mice with a null mutation of LNR, the transport of NT-4 and BDNF, but not NGF, was dramatically reduced. These observations demonstrate a selective role for LNR in retrograde transport of the various neurotrophins from distinct target regions in vivo.

Animals↗
PubMed1995

Self-reports of HIV risk behavior by injecting drug users: are they reliable?

While most studies of AIDS risk behavior rely on self-reports, few studies have assessed the reliability of these reports. The present study examines self-reports of drug-related and sexual risk behavior among pairs of injecting drug users (IDUs) recruited from the streets in New York City. Since both members of the pair were interviewed, it was possible to compare their responses in order to assess reliability. Subjects reported on their contacts' demographic data (age, gender, race/ethnicity) and on shared risk behaviors, including syringe sharing. Despite the private and/or illegal nature of AIDS risk behaviors, IDU subjects were generally reliable in their reports of both demographic and AIDS risk behaviors.

Adolescent↗
PubMed1995

Neuronal sprouting in mouse sensory ganglia infected with herpes simplex virus type 2 (HSV-2): induction of growth-associated protein (GAP-43) and ultrastructural evidence.

Herpes simplex virus (HSV) is neurotropic and when inoculated on the mouse footpad is retrogradely transported to the associated dorsal root ganglia (DRG), where infection is established. Previous observations suggest that, after HSV infection, sensory ganglion neurons may mount a sprouting response. In our HSV-infected DRG model, we investigate this issue by (1) examining expression of growth-associated protein (GAP-43), a molecule known to be induced by growing axons, and (2) determining ultrastructurally whether HSV-infected dorsal roots contain neurites. In a time course study, we show that GAP-43 is induced both in HSV-infected DRG and their central processes. The increase in GAP-43 is first seen 2 weeks following unilateral footpad inoculation in both cell bodies and dorsal roots, and is sustained at 1 month post inoculation in roots but not in perikarya. Large bundles of unmyelinated small caliber axons, lacking Schwann cell ensheathment, are observed by electron microscopy in dorsal roots 2 weeks and 1 month following inoculation. These profiles resemble developing or regenerating neurites and are rarely seen in roots of mock-infected or uninfected controls. The increased GAP-43 immunoreactivity and ultrastructural changes shown here, in conjunction with previously documented selective neuropeptide and enzyme alterations, confirm that a sprouting response is mounted in sensory ganglia following acute HSV infection.

Animals↗