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R H Ward

Publications and source records attributed to R H Ward.

At least 73 records · Page 4Linked to original sources
PubMed1987

Antibody-dependent cytotoxicity on chicken red blood cell targets mediated by the U937 cell line.

We have characterized a model system for the study of antibody-dependent cytotoxicity (ADCC) mediated by human macrophages and monocytes. The U937 cell line is used as a source of effector cells. We confirmed a previous report (Gidlund et al., 1981) that U937 can be activated using PMA to kill in ADCC, and the characteristics of the observed cytotoxicity are described. Activation of effectors was maximal after 20-hr preincubation in the presence of 10 ng/ml PMA. In these conditions, lysis was approximately 70% in 2 hr at an effector to target ratio of 5:1. Activation correlated with the expression of complement receptors CR1 and CR3. No antibody-independent cytotoxicity was observed. The effects of various inhibitors of oxygen species were investigated: the lysis obtained in the above conditions was inhibited at 50% in the presence of either 450 mM dimethyl sulphoxide or 30,000 U/ml catalase, but superoxide dismutase (up to 10,000 U/ml) or ferricytochrome c (up to 2 mM) had no effect. The same inhibition was observed with 40 mM desferrioxamine or with 1 mM 0-phenanthroline, which are both iron scavengers, or in the presence of 300 microM colchicine or 1.5 microM dihydrocytochalasin B, which are two inhibitors of cytoskeletal functions. An identical effect was obtained in the presence of 1 TIU/ml bovine pancreas trypsin inhibitor, whereas soya bean trypsin inhibitor, which is more specific, had no effect up to 5000 BAEE U/ml. No inhibition was seen with protein synthesis inhibitors as cycloheximide or puromycin at 40 micrograms/ml. The significance of these results is discussed.

Animals↗
PubMed1986

Effect of chorionic villus sampling and early pregnancy counselling on uptake of prenatal diagnosis.

An early pregnancy counselling clinic was introduced to improve the uptake of prenatal diagnosis and to offer chorionic villus sampling to women aged 38 and over by their expected date of delivery. Ninety eight (62%) unselected older mothers were seen before 11 weeks' gestation, and 23 (32%) of those with viable pregnancies elected to undergo chorionic villus sampling compared with 38 (52%) electing amniocentesis. A quarter of the patients booking before 11 weeks had a miscarriage. Because of the future potential demand for chorionic villus sampling counselling during pregnancy and referral of eligible patients should occur as early as possible.

Adult↗
PubMed1986

Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia.

Decreased plasma high-density-lipoprotein (HDL) cholesterol and apolipoprotein A-I levels have been associated with premature coronary artery disease. We identified a PstI restriction-endonuclease site flanking the human apolipoprotein A-I gene at its 3' end that is polymorphic. The absence and presence of this site, as determined by genomic blotting analysis of PstI-digested chromosomal DNA with the use of an apolipoprotein A-I gene probe, were associated with 3.3-kb and 2.2-kb hybridization bands, respectively. The 3.3-kb band appeared in 4.1 percent of 123 randomly selected control subjects and in 3.3 percent of 30 subjects with no angiographic evidence of coronary artery disease. In contrast, among 88 patients who had severe coronary disease before the age of 60, as documented by angiography, the 3.3-kb band occurred in 32 percent (P less than 0.0001). It was also found in 8 of 12 index cases (P less than 0.0001) of kindreds with familial hypoalphalipoproteinemia. In the two patient groups, the allele frequencies of the site that produced the 3.3-kb band were 17 and 42 percent, respectively, as compared with an allele frequency of only 2 percent in the control populations. Within kindreds with familial hypoalphalipoproteinemia and among first-degree relatives of patients with coronary artery disease, the 3.3-kb band was associated with decreased HDL cholesterol levels. Among all patients with coronary artery disease, 58 percent had HDL cholesterol levels below the 10th percentile of normal values; however, this frequency increased to 73 percent when patients with the 3.3-kb band were considered. These findings indicate that the polymorphism in the region between the apolipoprotein A-I and apolipoprotein C-III genes may be a useful marker for the risk of premature coronary artery disease and familial hypoalphalipoproteinemia.

Age Factors↗
PubMed1986

Radioiodide transfer across sheep placenta.

Unidirectional transplacental clearances of radioiodide were calculated from the net radioiodide fluxes after injection into fetal and/or maternal circulations of 33 catheterized conscious sheep. Maternofetal potential difference (PD) was also recorded. Clearance reached a steady state 20 min after bolus injection. Fetomaternal clearance was related to PD. Bidirectional clearance ratios measured in five experiments showed a significant divergence from the value for passive flux predicted from the measured PD, and in four experiments these ratios were also significantly different from unity, this result being incompatible with passive flux even if the transplacental PD is assumed to be zero. Injection of thiocyanate or iodide reduced radioiodide clearance. Fetomaternal clearance of radioiodide was halved by an increase in fetal plasma iodide concentration of approximately 0.1 mM. There appears to be an inhibitable iodide-transporting site capable of active transport in either direction.

Animals↗
PubMed1985

First trimester prenatal diagnosis and detection of carriers of haemophilia A using the linked DNA probe DX13.

Although the use of a gene specific deoxyribonucleic acid (DNA) probe is the method of choice for detecting carriers of genes for rare genetic disorders, there will always be families in which such probes cannot be used because key subjects are not informative for restriction fragment length polymorphisms in or around the gene. In these cases closely linked DNA markers have to be used. An X chromosome specific DNA probe, DX13, which is closely linked to the haemophilia A locus on the X chromosome, was used for early prenatal diagnosis in two cases and to detect carriers in a series of nine possible heterozygote women. The first reported crossover between DX13 and the factor VIII:C locus was observed in this study. There are complexities inherent in using any linked DNA probe for assignment of genes, but such techniques are clinically important.

Female↗
PubMed1985

Diagnostic fetal blood sampling for the haemoglobinopathies--10-year experience.

The development of methods for fetal blood sampling in the second trimester of pregnancy offers the possibility of fetal diagnosis for couples at risk for having children with a haemoglobinopathy. We review the evolution of 10 years' experience of fetal blood sampling for 681 patients. The obstetric risk associated with the procedure has fallen from an initial 15% (in the first 87 pregnancies) to about 3%, in parallel with increased experience, improved ultrasound control, identification of the causes of complications and implementation of simple steps to avert them.

Diseases in Twins↗
PubMed1985

Age of onset in siblings of persons with juvenile Huntington disease.

The age of onset distribution of Huntington disease (HD) has been defined for siblings of patients who exhibit the disease before age 20. The mean age of onset for the siblings of juvenile onset cases is 26.8 years, which is significantly less than the mean age of onset (39.8) observed in siblings of non-juvenile cases. We have shown that the curve for age of onset in the general affected population is significantly different from that of the juvenile sibships. Furthermore, the significant regression equation suggests that the 'expected age of onset' of a sibling can be predicted from a knowledge of the age of onset of the juvenile proband. This information can be used to predict a range of age of onset for those sibs of juvenile patients who are likely to be asymptomatic heterozygotes with DNA polymorphism studies.

Adult↗
PubMed1985

Characterization of patients with an increased susceptibility to bacterial infections and a genetic deficiency of leukocyte membrane complement receptor type 3 and the related membrane antigen LFA-1.

Three children from two unrelated families had a history of recurrent bacterial infections, and their neutrophils were shown to have deficient phagocytic and respiratory responses and possible deficiencies in chemotaxis or adherence. Their neutrophils were strikingly deficient in the ability to ingest or give a respiratory burst in response to unopsonized bakers' yeast or zymosan (Z). Tests for neutrophil and monocyte CR1 (C3b/iC3b receptor) and CR3 (iC3b receptor) demonstrated rosettes with both EC3b and EC3bi. However, EC3bi were bound only to CR1, and not to CR3, because EC3bi rosettes were inhibited completely by anti-CR1. Neutrophils, monocytes, and natural killer (NK) cells also did not fluorescence stain with monoclonal antibodies specific for the alpha-chain of CR3 (anti-Mac-1, anti-Mol, OKM1, and MN-41). Quantitation of C receptors with 125I monoclonal anti-CR1 and anti-CR3 indicated that neutrophils from each patient expressed normal amounts of CR1 per cell but less than 10% of the normal amount of CR3. Examination of neutrophils by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that a normal glycoprotein of approximately 165,000 daltons was missing. Immunoblotting of these gels indicated that the missing band was the alpha-chain of CR3. Subsequent analysis of all three patients' cells also demonstrated a deficiency of LFA-1 alpha-chain and the common beta-chain that is shared by the CR3/LFA-1/p150,95 membrane antigen family. The deficiency of LFA-1 probably explained the absent NK cell function, as normal NK cell activity is inhibited by anti-LFA-1 but not by anti-CR3. The reduced phagocytic and respiratory responses to Z were probably due to CR3 deficiency, because treatment of normal neutrophils with anti-CR3, but not anti-FLA-1, inhibits responses to Z by 80% to 90%. Ingestion of Staphylococcus epidermidis by normal neutrophils was shown to be partially inhibited by monoclonal antibodies to the alpha-chain of either CR3 or LFA-1, and monoclonal antibody to the common beta-chain inhibited ingestion by 75%. Thus, both CR3 and LFA-1 may have previously unrecognized functions as phagocyte receptors for bacteria. The absence of this type of nonimmune recognition of bacteria by these children's neutrophils may be one of the reasons for their increased susceptibility to bacterial infections.

Antigens, Surface↗
PubMed1985

Monoclonal antibodies which react with lymphocyte-lysed target cells and which cross-react with complement-lysed ghosts.

Monoclonal antibodies were raised against a human natural killing system and screened against targets lysed either by human lymphocytes in antibody-dependent cellular cytotoxicity (ADCC), or by human complement. Two monoclonals were identified which bound specifically to both types of killed targets. More detailed studies with one antibody showed that it inhibited ADCC, both as intact antibody and as the F(ab')2 fragment. Intact antibody enhanced natural (NK) killing, although the F(ab')2 fragment inhibited NK killing. The data support the hypothesis that lymphocyte-mediated killing involves a complex analogous in nature to the complement membrane attack complex. In addition, the antibodies provide evidence to suggest that this complex has antigenic determinants in common with the complement membrane attack complex, and indicate the possibility that the two systems are derived from a common ancestor.

Animals↗
PubMed1984

Effect of fetal diagnostic testing on birth-rate of thalassaemia major in Britain.

A programme of prospective heterozygote detection and counselling, fetal diagnostic testing, and abortion of fetuses affected by thalassaemia major introduced in Britain in 1977 has proved highly acceptable to at-risk couples of Cypriot and East African Asian origin, but less so to couples of Pakistani origin. However, many at-risk couples are still not detected prospectively, the proportion of thalassaemia-major births prevented was only 32% by the end of 1981, and there is little evidence of a further fall since then. The thalassaemia-major birth-rate had fallen by 60% in Cypriots and by 20% in East African Asians, but it had not fallen at all in Pakistanis. Improved approaches to fetal diagnosis of thalassaemia major are becoming available, so a concerted effort is needed to inform all the at-risk ethnic groups of the existence of the problem and the possibility of detection of affected fetuses.

Africa, Eastern↗
PubMed1984

Age structure and the distribution of rare genetic diseases.

Equilibrium frequencies of rare deleterious genes in an age-structured population have been studied by using mathematical models. In the models, variable age-of-onset and variable penetrance of a trait have been incorporated. Numerical analyses show that the equilibrium gene frequencies can be approximated extremely well to those in nonoverlapping generations, as Haldane [1927] claimed. This property of rare deleterious genes in an age-structured population is important because population dynamics of such genes in a finite population can be studied easily.

Age Factors↗
PubMed1984

Arthritis confined to knee joints. Synovial lymphocyte responses to microbial antigens correlate with distribution of HLA.

The responses of synovial lymphocytes to Chlamydia/Ureaplasma and to enteric antigens were studied in 31 patients with arthritis confined to knee joints, 15 patients with sexually-transmitted Reiter's syndrome, 9 with enteric Reiter's syndrome, and 24 with rheumatoid arthritis. The frequency of HLA antigens was studied in 28 patients with knee joint arthritis; this group was characterized by elevated frequencies of HLA-A2 and DR1. A subgroup of 8 responders to Chlamydia/Ureaplasma was characterized by an increase of HLA-Bw44 and DR7 or 8, while a subgroup of 8 responders to enteric antigens was characterized by increases of HLA-A1 and DR5. The frequency of HLA-B27 in the groups responding to antigens was 25-30%, less than half the frequency in patients with Reiter's syndrome.

Adolescent↗
PubMed1983

Method of sampling chorionic villi in first trimester of pregnancy under guidance of real time ultrasound.

Samples of chorionic villi were obtained in the first trimester by aspiration using a cannula passed transcervically under the guidance of real time ultrasound. In initial studies in 47 anaesthetised patients immediately before therapeutic abortion a method was developed giving a success rate of 89%. In 10 patients successful sampling was performed as an outpatient procedure without anaesthesia. In all, seven diagnostic procedures were undertaken and four of the five unaffected pregnancies continued. The technique of chorionic villous sampling using real time ultrasound is simple to learn and yields material for biochemical analysis and chromosomal study without the need for tissue culture. The exact obstetric risk, however, remains to be defined.

Catheterization↗