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Biomedical subjects

C Harmon

Publications and source records attributed to C Harmon.

At least 19 recordsLinked to original sources

Health insurance and health services utilization in Ireland.

The numbers buying private health insurance in Ireland have continued to grow, despite a broadening in entitlement to public care. About 40% of the population now have insurance, although everyone has entitlement to public hospital care. In this paper, we examine in detail the growth in insurance coverage and the factors underlying the demand for insurance. Attitudinal responses reveal the importance of perceptions about waiting times for public care, as well as some concerns about the quality of that care. Individual characteristics, such as education, age, gender, marital status, family composition and income all influence the probability of purchasing private insurance. We also examine the relationship between insurance and utilization of hospital in-patient services. The positive effect of private insurance appears less than that of entitlement to full free health care from the state, although the latter is means-tested, and may partly represent health status.

Attitude to Health↗

Protection against cyclophosphamide-induced alopecia and inhibition of mammary tumor growth by topical 1,25-dihydroxyvitamin D3 in mice.

Twenty-one-day-old BALB/c mice were shaved on the back to synchronize hair growth. On day 30 or 31, when at least 90% of mice exhibited hair regrowth in the shaved area, 1,25(OH)2D3 was applied topically to the shaved area daily for 5 days. On the 6th day, cyclophosphamide (Cytoxan, CTX) was injected i.p. to induce hair loss in the shaved area. Alopecia was induced in a dose-dependent manner by CTX treatment within 1 to 2 weeks. This effect was reduced significantly if mice were pre-treated with 1,25(OH)2D3, though only slight protection was observed in female mice. Interestingly, this 1,25(OH)2D3-mediated protection against hair loss was attenuated in male mice but became more significant in female mice when they were inoculated with the EMT-6 murine mammary tumor prior to treatment. More importantly, topical treatment with 1,25(OH)2D3 alone was able to inhibit EMT-6 tumor growth in both male and female BALB/c mice. Furthermore, 1,25(OH)2D3 pre-treatment also augmented the anti-tumor effect of CTX. Our results demonstrate that topical application of 1,25(OH)2D3 can protect against CTX-induced alopecia both in tumor-free and in tumor-bearing mice in a sex-dependent manner. Moreover, 1,25(OH)2D3 was shown, either alone or in combination with CTX, to inhibit tumor growth.

Administration, Topical↗

Membrane transport of long-chain fatty acids: evidence for a facilitated process.

In mammalian cells, membrane uptake of long-chain fatty acids is mediated by two separate components; a passive component that is a linear function of the concentration of free fatty acid in the extracellular medium and a saturable component that exhibits the characteristics of a protein-facilitated process. This review summarizes the body of work that has accumulated related to the mechanism of fatty acid transport. Evidence in support of a facilitated uptake process is presented with relation to the different cell types or membrane systems where it was collected. The evidence includes saturation kinetics, competition between different substrates, and sensitivity to a variety of inhibitors. Recent knowledge related to membrane proteins thought to be implicated in the uptake process is reviewed. Factors that may modulate uptake or alter the relative contribution of passive versus facilitated components are briefly discussed. These include the molar ratio of fatty acid to its physiological carrier, plasma albumin and the metabolic or hormonal milieu.

Animals↗

A 1.1-Mb transcript map of the hereditary hemochromatosis locus.

In the process of positionally cloning a candidate gene responsible for hereditary hemochromatosis (HH), we constructed a 1.1-Mb transcript map of the region of human chromosome 6p that lies 4.5 Mb telomeric to HLA-A. A combination of three gene-finding techniques, direct cDNA selection, exon trapping, and sample sequencing, were used initially for a saturation screening of the 1.1-Mb region for expressed sequence fragments. As genetic analysis further narrowed the HH candidate locus, we sequenced completely 0.25 Mb of genomic DNA as a final measure to identify all genes. Besides the novel MHC class 1-like HH candidate gene HLA-H, we identified a family of five butyrophilin-related sequences, two genes with structural similarity to a type 1 sodium phosphate transporter, 12 novel histone genes, and a gene we named RoRet based on its strong similarity to the 52-kD Ro/SSA lupus and Sjogren's syndrome auto-antigen and the RET finger protein. Several members of the butyrophilin family and the RoRet gene share an exon of common evolutionary origin called B30-2. The B30-2 exon was originally isolated from the HLA class 1 region, yet has apparently "shuffled" into several genes along the chromosome telomeric to the MHC. The conservation of the B30-2 exon in several novel genes and the previously described amino acid homology of HLA-H to MHC class 1 molecules provide further support that this gene-rich region of 6p21.3 is related to the MHC. Finally, we performed an analysis of the four approaches for gene finding and conclude that direct selection provides the most effective probes for cDNA screening, and that as much as 30% of ESTs in this 1.1-Mb region may be derived from noncoding genomic DNA.

Amino Acid Sequence↗

Role of tyrosine kinases, protein kinase C, and protein kinase A in the regulation of interferon-alpha production induced by herpes simplex virus type 1.

Herpes simplex virus 1 (HSV-1) is able to induce interferon-alpha production by natural IFN-alpha-producing cells. In this study, signal transduction in this process was examined. It was found that sequestering of calcium by EGTA abolished IFN-alpha induction by HSV-infected cells. Stimulation of human PBMC by HSV-1-infected fibroblasts resulted in the production of inositol triphosphate (InsP3) and tyrosine phosphorylation of cellular proteins. The protein kinase C inhibitor, H7, and the tyrosine kinase inhibitor, herbimycin A, were able to suppress IFN-alpha gene expression as determined by IFN bioassay and RT-PCR. An IFN-alpha-specific ELISpot assay revealed that herbimycin A and H7 remarkably decreased the number of IFN-alpha-producing cells. PMA or calcium ionophore A23187 alone did not increase IFN-alpha production. However, PMA in conjugation with ionophores increased IFN-alpha production as early as 2 h. HA1004 and 2',5'-dideoxyadenosine, which are potent inhibitors of PKA pathway, had no effect on IFN-alpha production. In contrast, BrcAMP, a specific PKA activator, inhibited the IFN-alpha secretion and number of IFN-alpha-producing cells and to a lesser extent reduced the level of IFN-alpha mRNA. Our results indicate that protein kinase C, tyrosine kinases, and protein kinase A are involved in the regulation of IFN-alpha production in response to HSV-1.

Base Sequence↗

Reliability of three clinical measures of muscle tone in the shoulders and wrists of poststroke patients.

Muscle tone was tested at the shoulders and wrists of 49 randomly selected poststroke patients with the use of resting joint position (SJP and WJP), resistance to passive movement or stiffness (SRM and WRM), and angle of appearance of resistance (SAR and WAR). Subjects were tested while seated with their arm supported in a suspension sling adapted for free movement. Five of the first and immediately repeated measurement pairs showed strong correlations and interrater reliability (SJP, .839; WJP, .900; SRM, .886; WRM, .904; SAR, .884 [p less than .05]). The sixth (WAR) showed moderate reliability (.618, p less than .05). Resting joint position measurements were most reliable among subjects with higher tone. The joint first measured had a slight order effect on SRM among subjects with higher muscle tone. Its second measurements were slightly increased over the first among those subjects whose shoulders were measured first and slightly reduced when measured immediately after the wrist. Reliable means of clinical evaluation of muscle tone at the shoulder and wrist are available if the influence of level of tone and the mutual influence of muscles tested are prudently considered.

Aged↗

Toxicity of coumarin (1,2-benzopyrone) on human peripheral blood mononuclear cells and human and murine bone marrow progenitor stem cells.

Coumarin (1,2-benzopyrone), in combination with cimetidine, has been subjected to separate clinical trials for the treatment of advanced renal cell carcinoma, malignant melanoma, and non-small cell lung cancer. While objective tumor regressions were observed only in renal carcinoma, no symptomatic or organ dysfunction toxicity was observed in any of the trials. The purpose of the present in vitro study was to determine the concentrations of coumarin and 7-hydroxycoumarin (7-HC) that would be toxic to human peripheral blood mononuclear cells (PB-MNC) and human and murine bone marrow (GM) progenitor stem cells. Coumarin was nontoxic for PB-MNC in concentrations up to 100 micrograms/ml. Concentrations of coumarin or 7-HC greater than or equal to 200 micrograms/ml produced significant suppression of human marrow GM stem cell activity. Coumarin greater than or equal to 25 micrograms/ml produced suppression of murine marrow GM stem cell activity. Differences in human and murine marrow sensitivity probably reflect interspecies differences in metabolism of coumarin. Correlations between toxic concentrations in vitro and maximally achievable serum concentration in vivo in humans await the results of further clinical trials.

Animals↗

Ro/SSA antigen in human epidermis.

It has been shown previously by an immunofluorescence technique, that whole serum from patients who have anti-Ro/SSA autoantibodies reacts with a component or components of the epidermis. We have now demonstrated by immunoblotting that the antigen identified in human epidermis by anti-Ro/SSA sera is Ro/SSA antigen, and that Ro/SSA antigen is present both in adult and in neonatal epidermis. The presence of this antigen in tissues which are injured in the anti-Ro/SSA-associated syndromes subacute cutaneous lupus erythematosus and neonatal lupus erythematosus supports the hypothesis that anti-Ro/SSA antibodies react with Ro/SSA antigen in the skin and are important in the initiation of tissue damage.

Adult↗

Characterization of immune response to oral administration of Streptococcus sobrinus ribosomal preparations in liposomes.

Gnotobiotic rats gastrically intubated with a total of 12.5 micrograms of Streptococcus sobrinus ribosomal protein incorporated into cholesterol-based liposomes had significantly (P less than or equal to 0.01) fewer carious lesions on their molar surfaces than did nonimmunized infected controls after challenge with a virulent organism. The immunized animals had significantly (P less than or equal to 0.01) lower numbers of molar-adherent S. sobrinus cells and higher levels of salivary immunoglobulin A antibodies to S. sobrinus whole cells and ribosomes than did the control group. Dose-response studies indicated that 12.5 micrograms of S. sobrinus ribosomal protein in liposomes induced slightly higher immune responses than did 62.5, 125.0, and 250.0 micrograms of ribosomal protein incorporated into liposomes. Intubation of rats with up to 250.0 micrograms of S. sobrinus ribosomal protein alone was no more effective in reducing the numbers of molar-adherent S. sobrinus cells than were nonimmunized infected controls, establishing that insertion of ribosomes into liposomes was required for inducing an effective immune response. These results indicate that oral administration of as little as 12.5 micrograms of S. sobrinus ribosomal protein incorporated into liposomes can protect rats from caries formation after challenge with the virulent organism by inducing specific salivary immunoglobulin A antibodies which can inhibit colonization by the challenged S. sobrinus.

Administration, Oral↗

Autoantibodies to SS-A/Ro in infants with congenital heart block.

Antibodies to SS-A/Ro have been proposed to be a serologic marker for the neonatal lupus syndrome, which is characterized by congenital heart block or cutaneous lupus or both. The antibodies occur in the mother and are transiently found in the child's serum. We examined an unselected series of 12 children with idiopathic CHB, isolated in 10 children and with cutaneous lupus lesions in two. Six of these children and their mothers were studied during the child's neonatal period, and six were studied retrospectively. All six neonates had SS-A/Ro autoantibodies. Nine of 12 mothers had SS-A/Ro autoantibodies. Of the seropositive mothers, one had systemic lupus erythematosus, two had sicca syndrome, one had photosensitivity, one had arthralgias, and four were asymptomatic. We propose that congenital heart block may be related to transplacental passage of maternal SS-A/Ro antibodies and that neonatal lupus may be the most common cause.

Adult↗

Immunogenetics of the neonatal lupus syndrome.

Infants with neonatal lupus erythematosus have congenital heart block, transient cutaneous lesions, or both. Mothers of these infants have SSA/Ro autoantibodies that are passed across the placenta to the fetus and that have been temporarily associated with the syndrome. Six families with neonatal lupus were studied by HLA typing. All seven infants had transient cutaneous lesions, congenital heart block, or both. Five of six mothers were asymptomatic and one had Sjögren's syndrome. Six of seven infants and all six mothers had antibodies to SSA/Ro in their sera. The infants became seronegative by age 8 months. Five mothers were positive for HLA-DR3, five for HLA-MB2, six for HLA-MT2, and six for HLA-B8. No HLA associations were seen in infants. Gene products of the DR or similar regions may be associated with autoantibody production but not with other events in tissue injury.

Antibodies, Antinuclear↗