Using dyadic data for a network analysis of HIV infection and risk behaviors among injecting drug users.
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Biomedical subjects
Publications and source records attributed to R Curtis.
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Focusing on the social environment as well as the individual should both enhance our understanding of HIV transmission and assist in the development of more effective prevention programs. Networks are an important aspect of drug injectors' social environment. We distinguish between (1) risk networks (the people among whom HIV risk behaviors occur) as vectors of disease transmission, and (2) social networks (the people among whom there are social interactions with a mutual orientation to one another) as generators and disseminators of social influence. These concepts are applied to analyses of data from interviews with drug injectors in two studies. In the first study drug injectors' risk networks converge with their social networks: 70% inject or share syringes with a spouse or sex partner, a running partner, or with friends or others whom they know. Qualitative data from interviews with injectors in the second study also show that the social relationships between drug injectors and members of their risk network are often based on long-standing and multiplex relationships, such as those based on kinship, friendship, marital and sexual ties, and economic activity. In the first study the vast majority of injectors, over 90%, have social ties with non-injectors. Injectors with more frequent social contacts with non-injectors engage in lower levels of injecting risk behavior. Risk settings may function as risk networks: injectors in this study who inject at shooting galleries are more likely than those who do not to rent used syringes, borrow used syringes and inject with strangers. Since the adoption of a network approach is relatively new, a number of issues require further attention. These include: how to utilize social networks among drug injectors to reduce risk through peer pressure; how to promote risk reduction by encouraging ties between injectors and non-injectors; and how to integrate biographical and historical change into understanding network processes. Appropriate methodologies to study drug injectors' networks should be developed, including techniques to reach hidden populations, computer software for managing and analyzing network data bases, and statistical methods for drawing inferences from data gathered through dependent sampling designs.
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Leukemia inhibitory factor (LIF) is a cytokine that affects the survival and differentiation of certain neuronal populations in vitro. To identify LIF-responsive neurons in the adult rat, we have demonstrated retrograde axonal transport of 125I-LIF to sensory and motor neurons. The accumulation of 125I-LIF by both cell types was significantly increased by prior sciatic nerve crush. Retrograde transport of 125I-LIF was inhibited by excess unlabeled LIF but not by related cytokines, indicating a specific receptor-mediated mechanism. Northern blot analysis revealed LIF expression in peripheral nerve that was increased in distal segments after axotomy. The correlation between LIF expression and increased retrograde transport following injury suggests that LIF plays a role in peripheral nerve regeneration.
In vitro studies have recently identified receptors and signal transduction systems for many neurotrophic factors. In vivo, however, target-derived factors act over distances that are too great to be accounted for by simple diffusion of factors or classical second messengers. The active translocation of neurotrophic factors from the axon to the cell body by receptor-mediated retrograde transport provides a means by which factors presented at distal sites may influence somal signal transduction. We hypothesize that retrograde transport of receptors and other receptor-associated proteins leads to signalling at the cell body.
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OBJECTIVES: To study how condom use in injecting drug users' (IDU) relationships differs according to whether they are HIV-infected, and to whether their sex partner is an IDU. DESIGN AND METHODS: A total of 317 street-recruited IDU were HIV-antibody tested and interviewed about 421 relationships with particular sex partners. RESULTS: Condoms were consistently (100%) used in sex between partners (during the previous 30 days) in 33% of these relationships, and their use was significantly more frequent in relationships of seropositive IDU and in relationships with non-IDU partners. In relationships between seropositive IDU and non-IDU, consistent condom use was reported to be high (68%); this remained unchanged under multivariate controls. CONCLUSIONS: Self-reported condom use by IDU in New York, with its relatively mature epidemic, appears to be concentrated where it may most reduce the spread of HIV to non-IDU heterosexuals, i.e., in relationships between infected IDU and non-IDU partners. Differential condom use by serostatus and by partners' drug injection should be incorporated into mathematical models of the HIV epidemic. Causes of the high level of condom use in this subset of relationships may include drug injector altruism and pressure by sex partners; prevention programs should develop ways to use both of these factors to motivate increased condom use.
Using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics, trends in female breast cancer rates were examined for the time period 1973-1989 for the age group 20-39 and contrasted with those for older ages. Only about 7% of breast cancers occur by the age of 40; the risk of developing breast cancer prior to the age of 40 is less than 1%. The incidence trends for women in the 20-39 age group have been essentially stable, whereas for women 40 and older the rates increased steeply during the 1980s (at a faster rate than anticipated based on historical trends) and then leveled off beginning in 1987. Breast cancer mortality has been much more stable over time than incidence. Up to age 40, blacks have a higher incidence than whites. Over age 40, white rates exceed those for blacks, and the absolute and relative differences in incidence increase with advancing age. For whites, 5-year relative survival rates improved with advancing age up to age 50. Blacks under the age of 30 had survival rates similar to whites, whereas, in the older age groups, whites had somewhat better survival rates overall and by stage. The occurrence of second cancers was also analyzed in women with a first invasive breast cancer. Cancers found to occur at higher than expected rates included leukemia and cancers of the breast, ovary, and lung.
Ciliary neurotrophic factor (CNTF) promotes the survival of several populations of neurons, including sensory and motor neurons. Although CNTF is abundant in adult sciatic nerve, the mature protein lacks a signal sequence and is not secreted; therefore, it has been proposed to act as a lesion factor. The identification of a functional CNTF receptor revealed ligand-specific phosphorylation cascades and gene induction. However, it is not clear how these signal-transducing events are elicited in neuronal cell bodies that may be distant from the source of CNTF. We report here that CNTF can be retrogradely transported by adult sensory neurons. More importantly, sensory and motor neurons both show greatly increased transport of CNTF following peripheral nerve lesion. Axotomy-induced increases in retrograde transport of neurotrophic factors may be an important response of neuronal cell bodies during regeneration.
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The alpha component of the receptor for ciliary neurotrophic factor (CNTF) differs from other known growth factor receptors in that it is anchored to cell membranes by a glycosylphosphatidylinositol linkage. One possible function of this type of linkage is to allow for the regulated release of this receptor component. Cell lines not normally responsive to CNTF responded to treatment with a combination of CNTF and a soluble form of the CNTF alpha receptor component. These findings not only demonstrate that the CNTF receptor alpha chain is a required component of the functional CNTF receptor complex but also reveal that it can function in soluble form as part of a heterodimeric ligand. Potential physiological roles for the soluble CNTF receptor are suggested by its presence in cerebrospinal fluid and by its release from skeletal muscle in response to peripheral nerve injury.
Canine DNA was cloned in M13 and screened for the presence of (dC-dA)n.(dG-dT)n repeats. Oligonucleotide primers were synthesised to the microsatellite flanking sequences and used in the polymerase chain reaction to amplify those loci from genomic DNA. The polymorphism of each microsatellite was estimated in a set of unrelated dogs.
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We have studied the distribution of the growth-associated protein GAP-43 in the spinal cord of adult rats by light and electron microscopy, using a new antiserum raised against GAP-43/beta-galactosidase fusion protein. We show that GAP-43 is present at all vertebral levels but is more concentrated in cervical and thoracic regions. In addition to heavy staining in the corticospinal tracts of the white matter, staining can be seen at the light microscopic level throughout the grey matter and is particularly heavy around the central canal and in the superficial dorsal horn. Electron microscopic examination revealed that GAP-43 immunostaining is confined to a subpopulation of axons and axon terminals. Staining occurs in small myelinated and unmyelinated fibres and in terminals which are mainly small and make single axodendritic or axosomatic synapses. Staining in such terminals occurs in the axoplasm but is heaviest immediately adjoining the axolema. Staining was not observed in dendrites, nor in large myelinated axons or large axon terminals. Our results indicate that GAP-43 is expressed in adult rat spinal cord in a subpopulation of small diameter fibres and axon terminals. The distribution and morphology of these terminals is consistent with several different possible origins including corticospinal projection neurons, small diameter primary afferent neurons, and descending raphe-spinal serotonin containing neurons.
The growth-associated protein-43 (GAP-43) is an axonal phosphoprotein which is expressed at high levels during development and is reinduced by regeneration in the PNS. Consequently it is believed to be a key molecule in the regulation of axonal growth. However, injury to the CNS does not result in significant regeneration and this has been suggested to correlate with a failure of central neurons to up-regulate GAP-43 after axotomy. We have examined a model of spinal cord injury which is unique in two respects; first dural integrity is maintained by compression of the cord with smooth forceps (thus excluding connective tissue elements) and, secondly, considerable axonal growth has been reported through the resulting lesion. Our previous studies have shown that GAP-43 is extensively distributed in the rat spinal cord (see accompanying paper), but here we have used anti-GAP-43 antiserum at a dilution which did not yield any immunostaining in normal cord. However, supranormal levels of GAP-43 were detected in cell bodies and axons around the lesion within four days of compression injury. Double immunostaining with the RT97 monoclonal antibody indicated that a small subpopulation of neurons local to the site of compression were axotomized and expressed GAP-43 and phosphorylated neurofilament epitopes in their cell bodies. Although damage to long axon tracts was extensive, there was no evidence of regeneration in white matter. On the other hand cavities which formed in grey matter provided an environment for axonal elongation. Immunolabelling with markers for astrocytes and endothelial cells was used to evaluate the interaction of elongating axons with endogenous CNS cell types. Sprouting axons, identified by the presence of elevated levels of GAP-43, did not appear to grow in contact with astrocytes but preliminary evidence suggested that newly formed capillaries provided an appropriate substrate.
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BACKGROUND: In syringe-mediated drug-sharing (backloading), injecting drug users (IDU) use their syringes to mix drugs and to give measured shares to other IDU by squirting drug solution into the syringes of other IDU. Backloading has been discussed as a potential HIV risk factor, but its role as an HIV transmission route has not been established empirically. METHODS: Six hundred and sixty IDU who had injected drugs in the previous 2 years were street-recruited from Bushwick, New York City through chain referral, tested for HIV antibody and interviewed about sexual and drug-risk behaviors. RESULTS: Receiving drugs via backloading in the previous 2 years was reported by 24.5% of the subjects. These subjects had significantly higher HIV seroprevalence than those who did not receive drugs by backloading (odds ratio, 2.2; 95% confidence interval, 1.5-3.1). Backloading remained positively and significantly associated with HIV seropositivity in stepwise logistic regression, and in a series of simultaneous logistic models controlling for sociodemographic variables and for sexual and drug risk variables. CONCLUSIONS: Backloading can be a route of HIV transmission among IDU and should be incorporated into risk-factor studies and HIV transmission modeling. Many IDU who avoid other high-risk drug-injection practices may overlook the risk of backloading. HIV prevention programs should warn IDU against syringe-mediated drug-sharing and work together to develop ways to avoid it.
Microsatellite sequences comprising (dC-dA)n.(dG-dT)n repeats have been isolated from canine libraries and sequenced. Oligonucleotide primers have been synthesized to the microsatellite flanking sequences and used in the polymerase chain reaction to amplify those loci from genomic DNA. The degree of polymorphism of each microsatellite was estimated in a set of unrelated dogs. It is concluded that of the 10 loci studied, nine are sufficiently polymorphic to be useful in genetic studies.