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Biomedical subjects

C Hawkes

Publications and source records attributed to C Hawkes.

18 recordsLinked to original sources
PubMed2002

Insulin-like growth factor-II/Mannose-6-phosphate receptor in the spinal cord and dorsal root ganglia of the adult rat.

The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a multifunctional transmembrane glycoprotein, which interacts with a number of molecules, including IGF-II and M6P-containing lysosomal enzymes. The receptor is widely distributed throughout the brain and is known to be involved in lysosomal enzyme trafficking, cell growth, internalization and degradation of IGF-II. In the present study, using autoradiographic, Western blotting and immunocytochemical methods, we provide the first report that IGF-II/M6P receptors are discretely distributed at all major segmental levels of the spinal cord and dorsal root ganglia of the adult rat. In the spinal cord, a high density of [(125)I]IGF-II binding sites was evident in the ventral horn (lamina IX) and in areas around the central canal (lamina X), whereas intermediate grey matter and dorsal horn were associated with moderate receptor levels. The dorsal root ganglia exhibited rather high density of [(125)I]IGF-II binding sites. Interestingly, meninges present around the spinal cord displayed highest density of [(125)I]IGF-II binding compared to any given region of the spinal grey matter or the dorsal root ganglia. Western blot results indicated the presence of the IGF-II/M6P receptor at all major levels of spinal cord and dorsal root ganglia, with little segmental variation. At the cellular level, spinal motorneurons demonstrated the most intense IGF-II/M6P receptor immunoreactivity, followed by interneurons in the intermediate region and deeper dorsal horn. Some scattered IGF-II/M6P immunoreactive fibers were found in the superficial laminae of the dorsal horn and dorsolateral funiculus. The meninges of the spinal cord also seemed to express IGF-II receptor immunoreactivity. In the dorsal root ganglia, receptor immunoreactivity was evident primarily in a subset of neurons of all diameters. These results, taken together, provide anatomical evidence of a role for the IGF-II/M6P receptor in general cellular functions such as transport of lysosomal enzymes and/or internalization followed by clearance of IGF-II in the spinal cord and dorsal root ganglia.

Animals↗
PubMed2001

Selective increases in HIV-specific neutralizing antibody and partial reconstitution of cellular immune responses during prolonged, successful drug therapy of HIV infection.

Because the immune response to HIV depends on viral gene expression, we examined the HIV-specific immune responses in persons whose viral load after highly active antiretroviral therapy (HAART) was <400 on at least 3 occasions over a 12-month interval. Eleven patients were identified. While there was little change in mean HIV-binding antibody (Ab) titers in this group, two persons mounted increases in HIV envelope-specific binding antibody. Neutralizing antibody (NAb) titers against a panel of HIV-1 primary isolates (BZ167, US1, and CM237) increased post-HAART (80% neutralization titer against US1, p = 0.06; against CM237, p = 0.04). The two persons with large increases in binding antibody also had increases in primary isolate NAb. Roughly half of HAART recipients had significant increases in neutralizing antibody to the primary isolates US1 and CM237. Compared with CD4-matched, non-HAART controls, there were significant increases in NAb against the subtype B primary isolate US1 (p < 0.0009); no increases were seen against more easily neutralized primary isolate BZ167. There were no differences after HAART in antibody-directed cellular cytotoxicity (ADCC). HAART resulted in a partial restoration of lymphoproliferative responses to recall antigens (tetanus and diphtheria). New responses developed to HIV Gag p24. No patient responded to HIV Env gp160 or gp120 either before or after HAART. The data underscore the lack of functional reconstitution of HIV-specific, CD4-mediated responses despite durable suppression of viral replication. In the setting of stable anti-HIV Ab levels, the development of increased NAb in certain individuals suggests that control of the virus by HAART may assist in immune control of HIV.

Anti-HIV Agents↗
PubMed2001

Clinical prognosis of patients with early-stage human immunodeficiency virus (HIV) disease: contribution of HIV-1 RNA and T lymphocyte subset quantitation.

Systems for the staging of individuals with human immunodeficiency virus type 1 (HIV-1) infection were developed 15 years ago. Subsequently, assays for quantitating HIV-1 RNA and immunophenotyping of lymphocyte subsets have been developed and validated. The utility of these assays for improved staging in early disease was evaluated in 256 HIV-infected adults (52% minority) with CD4 counts > or = 400 cells/microL followed in U.S. military medical centers before the highly active anti-retroviral therapy era. HIV viral load (RNA) was quantitated; the frequencies of select CD4+ immunophenotypes were determined in 112 subjects. The results were analyzed in relation to three outcome measures: death, first acquired immunodeficiency syndrome-defining opportunistic infection, and CD4 count < or = 200 cells/microL. Serum RNA level and CD4 count were each found to be predictive of all three outcomes. In addition, increases in the T-cell subsets CD28-CD4+ and CD29+CD26-CD4+ were found to be independently predictive of more rapid progression. The classification of early-stage HIV patients is improved by the quantitation of both viral RNA and T-lymphocyte subsets.

Adult↗
PubMed1998

CD38 expression on cryopreserved CD8+ T cells predicts HIV disease progression.

Previous studies have revealed that the expression of CD38 on CD8+ T cells is a strong predictor of disease progression in human immunodeficiency virus (HIV)-infected individuals. Those studies were performed using fresh patient samples over an extended trial period. After demonstrating the validity of assay results on cryopreserved cells, we performed a retrospective study using frozen cell samples to determine the predictive value of CD38 expression in patients with CD4 counts above 400 cells/microl. The CD38 expression as measured by antibody binding capacity and the CD38 median channel were shown to be associated with time to new opportunistic infection or death (both P < 0.001). These results suggest that CD38 expression on CD8+ T cells, whether fresh or frozen, provides a useful predictor of HIV disease progression.

ADP-ribosyl Cyclase↗
PubMed1998

Targeting speech processing strengths to facilitate pronunciation change.

This paper reports investigation and intervention with a 5 year old boy (AG) with unintelligible speech. Phonological analysis and psycholinguistic investigation allowed exploration of his speech processing strengths and difficulties as a basis for planning intervention. It was hypothesised that intervention which exploited his strengths, without focusing directly on his difficulties, would enable him to discover how to modify his pronunciation patterns. Significant positive changes had occurred by age 6 years.

Child, Preschool↗
PubMed1997

Streptococcus pyogenes type 5 M protein is an antigen, not a superantigen, for human T cells.

M proteins are coiled-coil dimers expressed on group A streptococcal cell surfaces. They have an important role in host antistreptococcal immunity and in poststreptococcal autoimmune sequelae. Controversy has arisen regarding whether type 5 M proteins are superantigenic for human T cells. To investigate this, we have produced and tested M5 in the form of two novel recombinant proteins. We found no evidence of superantigenicity using either recombinant whole M5 protein (rM5) or recombinant pep M5 protein (rpepM5) to activate peripheral blood mononuclear cells (PBMC) from healthy adult volunteers. Short-term, rM5-specific T-cell lines from different subjects were uniformly self-APC restricted and showed no consistent pattern of TCR V beta usage. A synthetic peptide of M5 residues 217-237 was found to contain epitope(s) recognized by some rM5-specific human T cells. PBMC responses to rM5 and rpepM5 in 3- and 7-day proliferation assays were characteristic of antigenic rather than superantigenic stimulation. We conclude that type 5 M protein activates human T cells as a conventional antigen.

Adult↗
PubMed1997

The professional carers' group: supporting group work for young sexual abusers.

OBJECTIVE: A centralized treatment project, for young people who have sexually abused others, describes how group-based work with potentially isolated local professionals may help a treatment program to maintain a systemic perspective. METHOD: The paper reviews relevant literature and outlines the context, format and goals of a Professional Carers' Group. RESULTS: Recurring themes, observed during the 30-week treatment programs, are subjected to clinical analysis. Two key areas are discussed: (1) cognitive-emotional processing of common reactions to work with sexual abuse; and (2) inter-professional communication to balance the requirements of child protection and therapy. CONCLUSION: Concurrent work with local professional networks may promote the clinical effectiveness of a treatment program for young perpetrators of sexual abuse. A Professional Carers' Group is one relatively low-cost approach which may help to integrate the work of a central treatment facility with that of distant, community-based, agencies.

Adolescent↗
PubMed1995

Olfactory function in atypical parkinsonian syndromes.

INTRODUCTION: Olfaction is markedly impaired in patients with idiopathic Parkinson's disease (IPD). This deficit contrasts with reports of preserved or only mildly reduced olfaction in patients with atypical parkinsonism. However, the sensitivity and specificity of olfactory function testing in the differential diagnosis of parkinsonian syndromes has not been studied. In addition, olfactory function in patients with corticobasal degeneration (CBD) is unknown. MATERIAL AND METHODS: Using the University of Pennsylvania Smell Identification Test (UPSIT) with a test score ranging from 0 to 40 we studied olfactory function in patients with IPD as well as other parkinsonian syndromes including CBD and progressive supranuclear palsy (PSP). RESULTS: UPSIT scores in 118 patients with IPD, 29 with MSA, 15 with PSP, and 7 patients with CBD, as well as in 123 healthy control subjects revealed a marked impairment in the IPD group in contrast to mild impairment in MSA patients and normal olfaction in PSP and CBD patients. An UPSIT score of 25/40 was associated with a sensitivity of 77% and a specificity of 85% in differentiating IPD from atypical parkinsonism. CONCLUSIONS: These results indicate that olfactory function is differentially impaired or preserved in distinct parkinsonian syndromes and that it might also have some value as a diagnostic pointer. Thus, preserved or mildly impaired olfactory function in a parkinsonian patient is more likely to be related to atypical parkinsonism such as MSA, PSP or CBD, whereas markedly reduced olfaction is more suggestive of IPD.

Adult↗
PubMed1994

Evaluation of cost minimization strategies of anaesthetic drugs in a tertiary care hospital.

A survey was undertaken to compare anaesthetic drug expenditures over a three-year period, to evaluate the impact of strategies offered to curtain continuously rising drug costs. Suggestions to control rising expenditures were based primarily on education of staff and residents regarding drug costs, emphasizing rational use of the more expensive drugs, and minimizing drug wastage. To assess the impact of these measures, a review of annual hospital budgets, global pharmacy expenditures, and anaesthetic drug expenditures was conducted for the period 1991 to 1993. Both absolute and proportional costs of anaesthetic drugs were compared, by year, according to six major classes: opioid analgesics (OA), muscle relaxants (MR), inhalational anaesthetic drugs (INH), intravenous anaesthetic drugs (i.v.), local anaesthetic drugs (LA) and a category labelled other drugs (OTH). In addition, the utilization patterns and unit price changes were compared for each drug for the periods 1991-92, and 1992-93. Total hospital drug costs increased from $7.1 M to $8.5M over the three years. During the same period, the cost of anaesthetic drugs decreased from $379K to $361K, despite an augmentation in annual case load from 12,507 to 13,076 surgical procedures. For the entire survey period, the mean cumulative anaesthetic drug cost was 4.6% of the pharmacy budget, or 0.24% of the hospital budget. Analysis by drug class revealed a $51K decrease in expenditures on OA. due to decreased utilization of fentanyl and alfentanil, and a decrease in the price of fentanyl. The increased expenditure on INH drugs was primarily due to an increase in acquisition costs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Incentives and barriers to physical activity for working women.

A questionnaire was completed by 393 working women to examine incentives and barriers to physical activity based on the stages of change from the transtheoretical model. Using Chi Square tests, differences were found across the five stages suggesting that work site programs be designed and tailored for women at different stages of readiness.

Adult↗
PubMedDate not supplied

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Hospital Units↗