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Biomedical subjects

R Harris

Publications and source records attributed to R Harris.

At least 271 records · Page 15Linked to original sources
PubMed1989

Evidence that matching for HLA antigens significantly increases transplant survival in 1001 renal transplants performed in the northwest region of England.

In the 20-year period from March 1968 to March 1988, 860 patients received 1001 renal transplants in the Northwestern Regional Renal Transplant Unit at Manchester Royal Infirmary. Through a continuing policy of avoiding mismatches for HLA antigens and lymphocytotoxic antibody crossmatching, transplant survival rates were found to correlate with the degree of HLA-A and B antigen mismatching from 1968 to 1978 and with HLA-B and DR antigen mismatching from 1979 to 1988. Mismatching for HLA-B and DR antigens was also found to correlate with transplant survival in highly sensitized patients and in patients transplanted since 1981, the "cyclosporine era." Recipients who were HLA-DR1 positive were found to have the highest graft survival compared to recipients negative for this antigen. In contrast, HLA-DR3 positive recipients had the poorest outcome. Transplants from HLA-DRw6 positive donors showed higher transplant survival rates than donor kidneys positive for any other HLA-DR antigen. A correlation of transplant survival with HLA-B and DR mismatching was seen whether kidneys were collected within our region or received through the UK Transplant Service. We conclude that avoidance of mismatching for HLA-B and DR antigens confers high transplant survival rates (91.1% at 5 years for 0 HLA-B and DR mismatches), and in order to achieve this rate for most recipients exchange of donor kidneys between transplant centers will be essential.

Adolescent↗
PubMed1989

Sequential flow cytometric analysis of cell-cycle related changes in LFA-1 (CD18/CD11a) expression by trisomy 21 (Down's syndrome) lymphoblastoid cells.

Lymphocyte function associated antigen 1 (LFA-1) is a heterodimeric leucocyte adhesion molecule comprising non-covalently associated 95 kD, CD18 and 180 kD, CD11a subunits. Lymphoblastoid cell-lines (LCL) derived from persons with Down's syndrome (Trisomy 21) exhibit increased expression of LFA-1 compared with normal LCL. Although this is probably due to a gene-dosage related increase in the synthesis of CD18, cell-cycle differences between Trisomy 21 (T21) and normal LCL could also influence LFA-1 expression. We have therefore analysed expression of CD18 on G1 and G2M cells using sequential flow cytometry. T21 and normal LCL were co-stained with the DNA-binding vital dye HO342 (Hoechst 33342), and with a CD18 monoclonal antibody. The LCL were first sorted on the basis of HO342 staining into G1 and G2M populations, and these fractions then analysed for CD18 expression. Irrespective of the stage of the cell-cycle, expression of CD18 was increased on T21 compared with normal LCL. Although more CD18 was detected on both T21 and normal G2M compared with G1 cells, the relative density of CD18 in G2M was less than in G1 because G2M cells were larger.

Antigens, CD↗
PubMed1989

21-hydroxylase deficiency families with HLA identical affected and unaffected sibs.

During our investigations of polymorphisms at, and in the immediate chromosomal vicinity of, the 21-hydroxylase locus in families with 21-hydroxylase deficiency, three families were found to show marked discordance in clinical features of HLA identical subjects. In one family, there is discordance between a boy with the simple virilising form of 21-hydroxylase deficiency and his two younger sisters, who are both HLA identical to their brother, but who have additional salt wasting features. In the other two families, one subject is severely affected and has very high 17-hydroxyprogesterone levels, but has an HLA identical sib who is asymptomatic and shows only slightly raised 17-hydroxyprogesterone levels. In all cases, HLA identity, as indicated by protein polymorphism studies (HLA-A, B, DR, C4A, C4B, and Bf typing), has been verified at the gene organisation level using 21-hydroxylase and complement C4 DNA probes. An HLA-Bw47 bearing haplotype in one of the latter families has not been transmitted to the affected child and appears to carry a normal 21-OHB allele and two genes which specify C4A allotypes.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Molecular genetics in the National Health Service in Britain.

A recent report from the Departments of Health draws attention to the value of DNA diagnosis for inherited diseases and the need for planning these services in the National Health Service. There is great potential for preventive medicine, but a major immediate benefit is the newfound ability to exclude the carrier state in many people at risk and to protect fetuses from abortion when, as in most cases, they are shown to be normal by DNA tests. However, the widespread application of these new techniques requires prior evaluation and general acceptance. This will only be obtained after public debate, education of professionals and the population, and the establishment of adequate non-directive genetic counselling services. Some of the points to be considered in setting up molecular genetics laboratories are described.

Cystic Fibrosis↗
PubMed1989

Neural tube defect recurrence after 'partial' vitamin supplementation.

A total of 227 mothers enrolled for periconceptional multivitamin supplementation because of previous neural tube defect (NTD) births took vitamins for less than the recommended minimum period (at least 28 days before conception until two menstrual periods have been missed). Of 213 examined infants/fetuses born to these partially supplemented mothers, two had NTD, one of whom followed four previous NTDs. The observed NTD recurrence rate is similar to that observed in fully supplemented mothers. A further 14 mothers started supplements before the second missed period but after the normal time of neural tube closure. Three of their offspring had NTD. The significance of this apparently high recurrence rate is discussed.

Ascorbic Acid↗
PubMed1989

Testing for cystic fibrosis using allelic association.

A particular haplotype defined by probes XV2c, KM19, and CS.7 at the D7S23 locus was found on 90% of chromosomes which carry cystic fibrosis (CF), but on only 11% of normal chromosomes in a UK sample of CF carriers. We show how such data can be used to calculate carrier risks for people with and without a family history of CF, and give examples of clinical applications. For parents or sibs of dead CF patients, phase and genotypes can often be assigned with only 1 to 2% error. However, this method is not suitable for prenatal testing where there is no history of CF; for couples with no family history, no fetus can be shown to be at more than 2% risk of being affected.

Adult↗
PubMed1989

Huntington's chorea: who cares?

The cost and place of care of 158 patients affected with Huntington's chorea in the North Western Region was analysed with respect to their age, domestic background and the nature and duration of their symptoms. Twenty-five per cent of patients are in residential care which is more costly and less desirable than supported care at home. The paper discusses the various options for the care of those with progressive long term neurological disorders.

Age Factors↗
PubMed1989

An evaluation and survey of enzyme immunoassay and fluorometric enzyme immunoassay tests for TSH and HCG.

Assays for human choriogonadotropin (HCG) and thyroid stimulating hormone (TSH) have typically been performed using radioisotopic procedures. Two newer, nonradioisotopic approaches, enzyme immunoassay (EIA) and fluorometric enzyme immunoassay (FEI), were evaluated for the determination of HCG and TSH. Two TSH EIA assays (Abbott, Hybritech) and one FEI assay (Dade) were compared with each other and an immunoradiometric (IRMA) assay. The FEI assay performed better than the EIA assays with a sensitivity of 0.3 microIU/ml, within-run closing volumes (CVs) of less than 4.5%, and a carryover of 0.7%. All of the assays correlated well with each other and the IRMA assay. Three HCG EIA assays (Abbott, Hybritech, Roche) and one FEI assay (Dade) were evaluated. Again, the FEI assay performed better than the EIA assays with a sensitivity of 1.3 mIU/ml, within-run CVs of 4.0% or less, and a carryover of 1.7%. The new generation of nonradioisotopic assays offers performance comparable to radioisotopic assays coupled with various degrees of automation. A clinical laboratory may not only take advantage of these methods but can choose an assay system that is well suited to its particular requirements.

Chorionic Gonadotropin↗
PubMed1989

A modified method for human bone marrow filtration prior to bone marrow transplantation.

A technique is described for filtering harvested bone marrow using disposable materials, namely a 4 x 4 inch piece of sterile gauze that is gently packed into the barrel of a 60-ml plastic disposable syringe, which is connected directly to a blood collection bag. The filtration of marrow directly into the collection bag eliminates additional filtration steps and therefore may potentially reduce the incidence of inadvertent microbial contamination. In this study we describe this filtering technique and compare it to the method described by Thomas and Storb. Numbers of granulopoietic progenitors (CFU-GM) and erythropoietic progenitors (BFU-E), total white cell counts, percentage of cells positive for the CD3 (OKT3) lymphocyte surface membrane marker, and volume changes were studied following filtration by each method. The two techniques were shown to be comparable in terms of these parameters. Furthermore, when compared with historical controls, this method resulted in a reduced incidence of microbial contamination compared to filtration using successive stainless steel screens.

Adolescent↗
PubMed1989

The incidence of corticosteroid side effects in chronic steroid-dependent asthmatics on TAO (troleandomycin) and methylprednisolone.

The purpose of this study was to determine the effect of troleandomycin (TAO)-methylprednisolone (MP) regimens on the incidence of corticosteroid-induced side effects. Retrospective analysis was performed on the charts of 29 adult chronic steroid-dependent asthmatics on regimens of TAO-MP. These 29 met our criteria of a minimum of 1 year on TAO-MP and at least 6 to 12 months on daily or alternate-day corticosteroids before TAO-MP was instituted. Charts were reviewed for nine known corticosteroid (CS) side effects, all previously identified side effects were excluded. Charts were also reviewed for TAO dose, MP dose, and dose/duration on CS therapy before TAO-MP regimen began. Patients on TAO at an average dose of 250 mg/d were able to wean to an average MP dose of 10.8 mg every other day from an average MP equivalent dose of 16.8 mg every other day before TAO. In spite of lower MP doses on TAO we found that 35% showed an increase in CS-induced side effects, some (three) had more than one side effect. Three patients developed cataracts (10%), two become hypertensive (6.8%), one developed diabetes (3%), one had a psychotic episode (3%), and one patient developed TB (3%) and had a spinal compression fracture. Sixty percent of these patients were on 8 mg or less of MP on an alternate-day basis. We found that in this group of 29 chronic steroid-dependent asthmatics the incidence of corticosteroid-related side effects was increased on TAO-MP regimens despite a reduction in corticosteroid dose.

Asthma↗
PubMed1988

Investigation by HPLC of the catabolism of recombinant tissue plasminogen activator in the rat.

The catabolism of recombinant tissue plasminogen activator (rt-PA) was investigated after injection of radiolabelled material into rats. Both Iodogen and Chloramine T iodination procedures yielded similar biological activity loss in the resultant labelled rt-PA and had half lives in the rat circulation of 1 and 3 min respectively. Complex formation of rt-PA was investigated by HPLC gel exclusion (TSK G3000 SW) fractionation of rat plasma samples taken 1-2 min after 125I-rt-PA injection. A series of radiolabelled complexes of varying molecular weights were found. However, 60% of the counts were associated with a single large molecular weight complex (350-500 kDa) which was undetectable by immunologically based assays (ELISA and BIA) and showed only low activity with a functional promoter-type t-PA assay. Two major activity peaks in the HPLC fractions were associated with free t-PA and a complex having a molecular weight of approximately 180 kDa. HPLC fractionation to produce these three peaks at various timed intervals after injection of 125I-rt-PA showed each to have a similar initial rate half life in the rat circulation of 4-5 min. The function of these complexes as yet is unclear but since a high proportion of rt-PA is associated with a high molecular weight complex with a short half life in the rat, we suggest that the formation of this complex may be a mechanism by which t-PA activity is initially regulated and finally cleared from the rat circulation.

Animals↗
PubMed1988

Child accident-mortality in the Northern Territory, 1978-1985.

The mortality in children who were aged 0-14 years in the Northern Territory in 1983-1985 was 2.5-times higher than it was for Australia generally over the same period. Total accidental-death rates over the period 1979-1983 in Aboriginal children were 2.2-times higher than in non-Aboriginal children. A trend towards an excess in Aboriginal child mortality was present in most categories except drowning and was particularly noteworthy for deaths due to natural and environmental causes (predominantly caused by box-jellyfish stings). Non-Aboriginal children experienced higher rates of death due to drowning than they did elsewhere in Australia; most of these occurred in domestic swimming-pools. A higher mortality was encountered in rural areas. The pattern of motor-vehicle-related deaths differed between Aboriginal children and non-Aboriginal children, with the former experiencing a greater number of deaths due to non-collision accidents that involved "loss of control". The implications of these findings for the development of appropriate preventive strategies is discussed.

Accidents↗
PubMed1988

Patterns of exon deletions in Duchenne and Becker muscular dystrophy.

A panel of patients with Duchenne and Becker muscular dystrophy (DMD and BMD) has been screened with the cDNA probes Cf56a and Cf23a, which detect exons in the central part of the DMD gene. One or more exons were deleted in 60% of patients. The deletions were mapped and prove to be heterogeneous in size and extent, particularly in DMD. Deletions specific to DMD and to BMD are described. Half of all BMD patients have a deletion of one particular small group of exons; smaller deletions within this same group produce the more severe DMD.

Chromosome Deletion↗