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S Crowe

Publications and source records attributed to S Crowe.

At least 19 recordsLinked to original sources
PubMed2000

Granulocyte-macrophage colony-stimulating factor inhibits HIV-1 replication in monocyte-derived macrophages.

BACKGROUND: Previous studies of the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on HIV-1 replication in macrophages have had inconsistent results, variously reporting no effect, augmentation or inhibition of viral replication. OBJECTIVE: To investigate the regulation of HIV-1 in monocyte-derived macrophages (MDM) by GM-CSF in vitro. METHODS: The role of GM-CSF on HIV-1 replication was assessed as supernatant and intracellular p24 antigen concentrations and by HIV-1 DNA and mRNA production under different culture conditions. Expression of CD4 and CCR5 receptors was examined. The effect of GM-CSF with an E21R mutation, which binds only to the alpha-chain of GM-CSF receptor, was used as an additional control. RESULTS: GM-CSF consistently suppressed HIV-1 replication in human MDM in vitro, as assessed by supernatant and intracellular p24 antigen concentrations and HIV-1 gag mRNA expression. The inhibitory effect of GM-CSF on HIV-1 replication was observed regardless of HIV-1 strain, source of GM-CSF, stage of MDM maturation or timing of GM-CSF exposure in relation to HIV-1 infection. The effect was dose dependent and reversed by addition of a neutralizing monoclonal antibody (4D4). Flow cytometric analysis of surface expression of CD4 and CCR5 indicates that GM-CSF does not affect HIV-1 entry into MDM. Analysis of intracellular HIV-1 DNA and mRNA suggests that HIV-1 replication is inhibited at or before transcription. E21R GM-CSF had no effect on HIV-1 replication in MDM. CONCLUSIONS: GM-CSF regulates HIV-1 replication in MDM, inhibiting HIV-1 replication through binding to the beta-chain of the GM-CSF receptor.

Cells, Cultured↗
PubMed2000

Psychological distress and family satisfaction following traumatic brain injury: injured individuals and their primary, secondary, and tertiary carers.

OBJECTIVE: To assess family psychosocial outcome following traumatic brain injury (TBI) in all family members, including relatives more peripheral to the person with the injury. DESIGN: A cross-sectional design was used to gather outcome data from individuals with TBI and primary, secondary, and tertiary carers, 19.3 months posttrauma. Multivariate analyses of variance (ANOVAs) ascertained differences in levels of psychological distress and family satisfaction within families. SETTING AND PARTICIPANTS: Seventy-nine families (65 individuals with TBI, 72 primary carers, 43 secondary carers, and 22 tertiary carers) were drawn from a sample of outpatients of three metropolitan, acute rehabilitation hospitals over a 12-month period. OUTCOME MEASURES: In addition to using the Family Satisfaction Scale (FSS), measures of psychological distress included the Beck Depression Inventory (BDI), State Anxiety Inventory (SAI), and Profile of Mood States (POMS). RESULTS: Although it was noted that a significant proportion of family members were not psychologically distressed and reported good family satisfaction, people with TBI remain at greater risk of poor psychosocial outcome than do their relatives. Of other family members, primary carers-particularly wives-are at greatest risk of poor psychosocial outcome, and a number of secondary and tertiary carers also displayed high levels of psychological distress. CONCLUSIONS: Male relatives (the majority of whom were secondary or tertiary carers) may report their distress in terms of anger and fatigue, rather than as depression and anxiety. Future research could develop TBI-specific measures of anger and fatigue as screening instruments to identify peripheral family members requiring assistance in adapting to TBI. Many families-despite their initial traumatic experience-eventually cope well, encouraging researchers and clinicians to focus future research efforts on those families who have made good adjustments to TBI.

Adaptation, Psychological↗
PubMed1998

Inhibitory processes in covert orienting in patients with Alzheimer's disease.

Previous studies of covert orienting in Alzheimer's disease (AD) have investigated exogenous and endogenous processes separately. We aimed to investigate how the 2 modes of orienting interact to control attention in healthy older participants and patients with AD. The covert orienting of visual attention task (COVAT) with abrupt onset cues was used in all experiments. In Experiments 1 and 2, predictive information was added to cues to initiate an endogenous orienting response. Results showed that healthy older participants were able to use endogenous processes to inhibit exogenous orienting. In contrast, patients with AD were unable to inhibit exogenous orienting to cues even when targets rarely appeared there. Experiment 3 investigated inhibition of return (IOR) in patients with AD. Both healthy older controls and patients with AD showed a normal IOR, suggesting that exogenous orienting processes are relatively unaffected by the normal aging process or in patients with AD. A model of covert orienting in which exogenous and endogenous orienting processes interact to control attentional behaviors is discussed.

Aged↗
PubMed1996

Human immunodeficiency virus type 1 replication is blocked prior to reverse transcription and integration in freshly isolated peripheral blood monocytes.

Peripheral blood monocytes are resistant to productive human immunodeficiency virus type 1 (HIV-1) infection in vitro immediately after isolation. No viral cDNA (either early or late transcripts) was detected by PCR in monocytes exposed to virus on the day of isolation. In contrast, in monocytes cultured for as little as 1 day, initiated and completed reverse transcripts were readily detectable within 24 h of infection with both HIV-1(Ba-L) and primary isolates. The levels of initiated, partially completed, and completed viral DNA copies found 24 h after infection increased progressively with time in culture before infection. Unlike quiescent T lymphocytes, there appeared to be no block or delay in the integration of viral DNA into the genome of susceptible cultured monocytes. With an Alu-PCR method designed to specifically detect proviral DNA being used, integration events were found within 24 h of infection in monocytes cultured for a day or more after isolation. No integration signal was found in freshly isolated monocytes up to 7 days following exposure to the virus. Cloning and sequencing of Alu-PCR-amplified DNA confirmed integration in HIV-1-infected cultured monocytes. Our finding that in vitro replication of HIV-1 is clearly blocked prior to the initiation of reverse transcription in freshly isolated peripheral blood monocytes suggests that these cells may not be susceptible to infection in vivo. Further studies to clarify this possibility and the nature of the block to infection should provide useful information for treatment strategies against HIV-1.

Base Sequence↗
PubMed1995

Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients.

A blood donor infected with human immunodeficiency virus-type 1 (HIV-1) and a cohort of six blood or blood product recipients infected from this donor remain free of HIV-1-related disease with stable and normal CD4 lymphocyte counts 10 to 14 years after infection. HIV-1 sequences from either virus isolates or patient peripheral blood mononuclear cells had similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the long terminal repeat (LTR). Full-length sequencing of one isolate genome and amplification of selected HIV-1 genome regions from other cohort members revealed no other abnormalities of obvious functional significance. These data show that survival after HIV infection can be determined by the HIV genome and support the importance of nef or the U3 region of the LTR in determining the pathogenicity of HIV-1.

Adult↗
PubMed1995

Arthritis not immobilization causes bone loss in the carrageenan injection model of inflammatory arthritis.

One suggested cause of the high turnover osteopenia of experimental inflammatory arthritis is disuse of affected joints. To compare the influence of immobilization or disuse, or both, with that of inflammatory arthritis on bone turnover, rabbits were placed into four groups. In group 1, arthritis was induced in the right knee by seven intra-articular injections of 1% carrageenan, over 49 days; in group 2, a plaster cast was applied to immobilize the right hindlimb in flexion; in group 3, arthritis was induced and the hindlimb was immobilized; and in group 4, nothing was done (control). The fluorescent label calcein was administered in drinking water (0.05%) ad libitum to all groups on days 22-36. On day 49, specimens were prepared for analysis of bone volume and new bone volume at a near site (right femur) and at remote sites (contralateral femur and ipsilateral humerus). The data were analysed by multiple regression and Bonferroni tests. In group 1, new bone volume was three times higher than in group 2 or 4 (p < 0.05 for each comparison); this indicated increased bone remodeling in the right femur. This contrasted with group 2, in which neither index of bone remodeling was changed. The combination of immobilization with arthritis resulted in more intense osseous effects of inflammatory arthritis, with a one-quarter decrease in bone volume (group 3, 30.99 +/- 2.50; group 4, 42.07 +/- 2.38, p < 0.05), as well as a 4-fold increase in new bone volume (p < 0.001) compared with group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Susceptibility of human monocytes to HIV type 1 infection in vitro is not dependent on their level of CD4 expression.

Monocytes from HIV-seronegative persons were analyzed for CD4 expression and susceptibility to infection with HIV-1 on the day of isolation and following 1, 2, and 7 days in culture. Although surface CD4 was readily detected on freshly isolated monocytes, these cells were relatively resistant to infection. After 1 to 2 days in culture, when surface expression of CD4 had decreased over 90% to near background levels, cells became susceptible to infection with HIV-1. CD4 expression on monocytes cultured for 7 days was more than four times higher than that on freshly isolated cells, and the cultured cells were fully permissive to infection. These observations suggest that the differing susceptibility of monocytes and monocyte-derived macrophages to infection with HIV-1 is not simply proportional to the level of surface CD4 expression.

Antigens, CD↗
PubMed1995

Functional analysis of the effects of a fully humanized anti-CD4 antibody on resting and activated human T cells.

A fully humanized anti-CD4 antibody was studied for its effects on resting and activated CD4 T cells. Whereas the antibody was poorly lytic, it induced dramatic down-modulation of CD4 expression on both types of cell. In order to down-modulate CD4 on resting, normal CD4 T cells there was an absolute requirement for FcR-mediated cross-linking of the anti-CD4 antibody, and only CD4 levels were affected. When activated cloned T-cell lines were studied there was no requirement for cross-linking and several other cell surface markers were also affected. Although the total cellular CD4 was reduced in the down-modulated cells, as judged by Western blot analysis, that CD4 which remained was associated with p56lck. The results are discussed in relation to the potential use of humanized anti-CD4 antibodies in the therapy of autoimmune disease and the choice of antibody isotype for such a therapeutic antibody.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1994

Silastic with polyacrylic acid filler: swelling properties, biocompatibility and potential use in cochlear implants.

We present a new hygroscopic implant material which consists of high-molecular-weight polyacrylic acid (PAA) as a filler in a Silastic matrix. The mixture swells upon immersion in bodily fluids; the degree of swelling depends on the ratio of PAA to Silastic and allows the design of implants that will achieve their final shape and size only after the implantation procedure. In vivo and in vitro biocompatibility tests reveal no adverse cellular or tissue responses. In cochlear implant development the material has been experimentally incorporated into intracochlear electrode arrays which curl after insertion, and in bacteriostatic devices for electrode fixation.

Acrylic Resins↗
PubMed1993

Analysis of interferon-alpha 2 sequences in human genomic DNA.

We have analyzed the genomic DNA sequence corresponding to the human interferon-alpha 2 (IFN-alpha 2) gene locus. In human lymphoblastoid Namalwa cells, we have detected sequences corresponding to IFN-alpha 2b and -2c, while in human KG-1 cells both IFN-alpha 2a and -2b were present. However, in 100 independent IFN-alpha 2 clones derived from 20 unrelated Caucasian volunteers, we found only sequences corresponding to IFN-alpha 2b. Statistical analysis of this result suggests that the sequences corresponding to IFN-alpha 2a and -2c are either rare allelic variants of this gene, occurring in only a minority of the Caucasian population, or are restricted to transformed cell lines.

Amino Acid Sequence↗
PubMed1993

The effects of methadone on immune function among injecting drug users: a review.

Methadone maintenance therapy is advocated as a major preventive strategy for the spread of the human immunodeficiency virus (HIV) and other blood-borne infectious agents among injecting drug users (IDUs) because of its effects in decreasing the frequency of injecting and presumably sharing of equipment. As an opioid agonist, methadone may share the direct and indirect immunoregulatory effects of other opioids, and thus affect susceptibility to, and the natural history of, HIV infection. Available evidence pertaining to methadone and immune function is reviewed. The long-term immunosuppression observed in heroin injectors on present (incomplete) evidence appears to be caused by factors associated with a drug-using lifestyle rather than by a direct action of heroin. Although data are conflicting, it is most likely that methadone does not significantly impair immune function and is safe for HIV-infected IDUs, possibly even allowing some improvement of immune function to occur. The increasing reliance placed on methadone maintenance to control the epidemic of HIV infection in IDUs requires that remaining uncertainties regarding methadone and immune function are clarified urgently.

Antibody Formation↗