Showing papers by "John Radcliffe Hospital published in 1982"
TL;DR: It is suggested that the hitherto unknown cell population detected with the monoclonal antibody Ki‐I in normal lymphoid tissue is the normal equivalent of H and SR cells.
Abstract: In this study the antigenic profile of Hodgkin (H) and Sternberg-Reed (SR) cells from cases of Hodgkin's disease was analysed using a large panel of monoclonal and polyclonal antibodies reactive with cells of lymphoid and haemotopoietic origin. The aim of this investigation was, firstly, to throw light on the origin of H and SR cells and, secondly, to determine whether there is any evidence to support recent suggestions that H and SR cells differ antigenically between different histological categories of Hodgkin's disease. Frozen sections (from 24 cases) and paraffin sections (83 cases) were stained by immunoenzymatic methods and the results compared with those obtained from staining a wide variety of reactive and neoplastic tissue samples (including examples of tuberculosis, sarcoidosis, malignant histiocytosis, histiocytosis X, osteomyelosclerosis and non-Hodgkin's lymphoma). The results revealed that H and SR cells of all types of Hodgkin's disease consistently lack markers found on null cells, B cells, T cells, cells of monocyte/macrophage series, interdigitating reticulum cells, dendritic reticulum cells and erythropoietic and thrombopoietic cells. However, H and SR cells constantly expressed an antigen detectable with the recently produced monoclonal antibody Ki-I. The vast majority of typical and lacunar type H and SR cells contained the granulocyte-related antigens detected by monoclonal antibodies TU5, TU6, TU9 and 3C4, whereas other more or less specific granulopoietic cell markers (such as peroxidase, chloroacetate esterade, lysozyme, cationic leukocyte antigen and OKMI) were consistently absent. H and SR cells in cases of nodular paragranuloma (nodular type of Hodgkin's disease with lymphocyte predominance) were not monotypic in light chain type (as has been previously reported), but rather contained chi and lambda chains within the same cells, as do typical and lacunar type H and SR cells. Immunostaining of normal and hyperplastic lymphoid tissue with the Ki-I antibody led to the detection of a new, as yet unidentified, small-cell population of unknown origin and function, which is present between, around, and within cortical follicles. It is concluded from these findings that H and SR cells constitute a unique cell type that differs in many properties from all other known cell types. Furthermore, H and SR cells of the various histological types of Hodgkin's disease are more closely related than previously believed. It is suggested that the hitherto unknown cell population detected with the monoclonal antibody Ki-I in normal lymphoid tissue is the normal equivalent of H and SR cells.
387 citations
TL;DR: The relation between the Apgar scores and the acid-base status of the babies at birth was assessed in a prospective study of 1210 consecutive deliveries and it was found that only 21% of babies with a 1 min Apgar score had an acid- base status.
340 citations
TL;DR: There were no significant differences between the children in the treated and untreated groups in standing and supine blood pressures, or fourteen tests of ability, and methyldopa seems safe to use in pregnancy and is probably preferable to other drugs from the point of view of the neonate and child.
256 citations
TL;DR: First-trimester diagnoses were successfully made in two fetuses atrisk for homozygous β thalassaemia and in one at risk for sickle cell anaemia by means of a simplified method for trophoblast biopsy together with restriction endonuclease analysis of fetal DNA.
244 citations
TL;DR: A monoclonal antibody that binds specifically to HLA-B27, B7, and B22 is described, which blocked complement-dependent cytolysis mediated by human HLA typing sera specific for B7 and B27.
236 citations
TL;DR: In this article, two monoclonal anti-human platelet antibodies have been used in an immunofluorescent assay to study megakaryocyte maturation, and the two antibodies were specific for platelets and Megakaryocytes.
202 citations
TL;DR: It is confirmed that En(a−) cells obtained fresh from three En( a−) individuals are indeed relatively resistant to invasion by Plasmodium falciparum although they are able to support parasite development and indicated that these cells may be a useful model in the search for a putative receptor for P. falcIParum.
Abstract: It has been suggested that one of the main factors which determines host susceptibility to different malarial parasites is the interaction of their invasive forms, merozoites, with specific receptors on the red cell membrane1–3. Thus the Duffy blood group determinants may be involved in the entry of Plasmodium vivax but not of Plasmodium falciparum into human red cells. When analysing red cells deficient in various blood group antigens, Miller et al. noted3 that two samples of En(a−) cells showed a reduction of invasion by P. falciparum4. These cells lack both the major transmembrane sialoglycoprotein, glycophorin A (or MN glycoprotein), and the independently segregating Wrightb (Wrb) antigen and also show increased glycosylation of band 3, the major membrane-penetrating glycoprotein. Despite this, En(a−) individuals are haematologically normal5. We have now confirmed that En(a−) cells obtained fresh from three En(a−) individuals are indeed relatively resistant to invasion by P. falciparum although they are able to support parasite development. Our results also indicate that these cells may be a useful model in the search for a putative receptor for P. falciparum.
181 citations
TL;DR: The ease of removal by dialysis, high solubilizing power and non-denaturing properties of this new class of detergents make them valuable reagents for membrane research.
Abstract: N-d-Gluco-N-methylalkanamide detergents have been synthesized. The detergents, which were produced in high yield and at low cost, compared favourably in biochemical studies with commonly used non-ionic detergents, including a chemically related n-alkyl glucoside. The ease of removal by dialysis, high solubilizing power and non-denaturing properties of this new class of detergents make them valuable reagents for membrane research.
171 citations
TL;DR: The permeability of cranial and lumbar dura to various substances including a number of narcotic analgesics was measured in vitro and indicated that drug molecular weight and rate of absorption are important determinants of the efficiency of dural transfer.
Abstract: SUMMARY The permeability of cranial and lumbar dura to various substances including a number of narcotic analgesics was measured in vitro. Preliminary data on human postmortem material is reported. Permeability had g linear relation to the inverse of the square root of molecular weight. This is the expected relationship for a diffusion process dependent upon molecular weight. The differential mass selectivity coefficients for lumbar and cranial dura were calculated; they were similar at 0.8 and 0.9. This was greater than for diffusion in simple liquids, but much less than that for biological lipid membranes. This suggests that the low rates of diffusion are a property of the thickness of the dura rather than any inherent impermeability. A simple model for the dural transfer of drugs is described, and applied to narcotics. Its purposes were to suggest: the factors involved in the dural transfer of drugs; the physicochemical properties of drugs relevant to their dural transfer; worthwhile measurements in future studies. The model indicates that drug molecular weight and rate of absorption are important determinants of the efficiency of dural transfer. Low molecular weight and slow absorption produce high dural transfers. When applied to narcotics, these factors could produce a difference of up to an order of magnitude in the amount transferred directly across the dura.
159 citations
TL;DR: It is shown that this monoclonal antibody, F10.44.2, is directed against a human antigenic determinant of restricted tissue distribution that is coded for by a gene, MIC4, which is on human chromosome 11, as shown by its reactivity with a panel of somatic cell hybrids.
Abstract: The monoclonal antibody, F10.44.2, is directed against a human antigenic determinant of restricted tissue distribution. In this report it is shown that this determinant is coded for by a gene, MIC4, which is on human chromosome 11, as shown by its reactivity with a panel of somatic cell hybrids. Synteny with an antigen recognized by another monoclonal antibody, W6/34, is demonstrated by hybrid and fluorescence-activated cell sorter analysis, although it is clear from absorption analysis that the determinants involved are on different molecules.
141 citations
TL;DR: It is suggested that both glycophorins A and B are involved in parasite invasion, indicate which parts of these molecules may be involved in this process, and provide the basis for a tentative model of parasite/red-cell interactions.
TL;DR: In this article, the authors report abnormal recovery of phosphocreatine (PCr) and pH after exercise of the forearm in two sisters, one having a mitochondrial NADH-coenzyme Q reductase deficiency and the other presumed to have the same defect on the basis of clinical symptoms, histology and biochemical studies of blood constituents.
Abstract: Mitochondrial myopathies are becoming increasingly recognized as uncommon causes of muscular disorders1 characterized by weakness and severe exercise intolerance. Electron micrographs of the muscle show gross abnormality of the mitochondrial structure. Such defects are expected to affect the energy metabolism of muscle but investigations in human subjects have necessarily been limited by the need for biopsy material. Following extensive phosphorus nuclear magnetic resonance (31P NMR) measurements on isolated organs, tissues and selected parts of live animals (see ref. 2 for review), it has become possible to observe non-invasively the energy metabolism of human muscle in vivo3–5. Here, we report abnormal recovery of phosphocreatine (PCr) and pH after exercise of the forearm in two sisters, one of whom has been shown to have a mitochondrial NADH-coenzyme Q reductase deficiency and the other presumed to have the same defect on the basis of clinical symptoms, histology and biochemical studies of blood constituents6. Our results, together with studies on normal subjects and patients with impaired glycogen metabolism, allow the assessment of the relative importance of oxidative and glycolytic regeneration of high-energy phosphates during exercise and recovery.
TL;DR: With an improved method for fitting baselines to human fetal heart‐rate traces, the patterns of episodic variations, accelerations and decelerations were similar in normal pregnancies and in 95 with mild hypertension and normal outcome, but the change in signal loss with gestational age was entirely due to the greater loss in episodes of high heart-rate variation.
TL;DR: Findings indicate that the Ca1 antibody may be useful in the diagnosis of malignancy in routine clinical practice where the morphological interpretation of the biopsy or cytological smear is in doubt.
TL;DR: Large variations in the pattern of normal fetal heart‐rate traces near term are described and the presence of flat or bimodal frequency distributions of pulse intervals in these traces complicates the derivation of a baseline by statistical methods.
TL;DR: In this paper, the authors describe the kinetics of inactivation by MgATP and its inhibition by branched-chain a-ketoacids, ADP and TPP; and identify the phosphoamino acid formed.
TL;DR: It is concluded that both methods of feeding induce progressive changes in circulating enteroinsular hormone levels, however, the endocrine milieu is different in the two groups, particularly since bolus‐fed infants experience marked cyclical surges in hormones after boluses of milk by 13 days of age.
Abstract: . Preterm infants receive gastric milk feeds as continuous infusions or intermittent boluses. It is not known whether these feeding methods have different effects on the development of digestive metabolism. We have measured plasma levels of insulin, pancreatic polypeptide (PP), gastric inhibitory polypeptide (GIP), gastrin, motilin, enteroglucagon (EG) and neurotensin (NT) in 19 preterm infants (28-34 weeks gestation) tolerating full enteral feeding from birth. 7 infants received human milk by continuous infusion, 12 infants were bolus fed. Hormones were measured in cord blood and at 6 and 13 days of age; samples were drawn preprandially in bolus fed infants. Both groups showed similar significant increases in plasma motilin, PP, NT and EG levels. At 13 days infusion fed infants had higher insulin. GIP and gastrin levels. No difference in rate of weight gain was seen in the two groups of infants. We conclude that both methods of feeding induce progressive changes in circulating enteroinsular hormone levels. However, the endocrine milieu is different in the two groups, particularly since bolus-fed infants experience marked cyclical surges in hormones after boluses of milk by 13 days of age. These differences in hormone release may affect metabolic homeostasis.
TL;DR: It is concluded that effects of starvation and alloxan-diabetes on the proportion of active complex in heart muscle are dependent on fatty acid oxidation.
Abstract: Intravenous administration of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid had no effect on the proportion of pyruvate dehydrogenase complex in the active form in heart, diaphragm or gastrocnemius muscles or in liver, kidney or adipose tissue of fed normal rats. The compound reversed the effect of 48h starvation (which decreased the proportion of active complex) in heart muscle, partially reversed the effect of starvation in kidney, but had no effect in the other tissues listed. The compound failed to reverse the effect of alloxan-diabetes (which decreased the proportion of active complex) in any of these tissues. In perfused hearts of fed normal rats, 2-tetradecylglycidate reversed effects of palmitate (which decreased the proportion of active complex), but it had no effect in the absence of palmitate. In perfused hearts of 48h-starved rats the compound increased the proportion of active complex to that found in fed normal rats in the presence or absence of insulin. In perfused hearts of diabetic rats the compound normalized the proportion of active complex in the presence of insulin, but not in its absence. Palmitate reversed the effects of 2-tetradecylglycidate in perfused hearts of starved or diabetic rats. Evidence is given that 2-tetradecylglycidate only reverses effects of starvation and alloxan-diabetes on the proportion of active complex in heart muscle under conditions in which it inhibits fatty acid oxidation. It is concluded that effects of starvation and alloxan-diabetes on the proportion of active complex in heart muscle are dependent on fatty acid oxidation. Insulin had no effect on the proportion of active complex in hearts or diaphragms of fed or starved rats in vitro. In perfused hearts of alloxan-diabetic rats, insulin induced a modest increase in the proportion of active complex in the presence of albumin, but not in its absence.
TL;DR: The Ca1 antibody provides a new method for the identification of malignant cells in pericardial, peritoneal, and pleural effusions.
TL;DR: There seems little justification for continued use of high doses of oral steroids with azathioprine after cadaveric renal transplantation, and the morbidity associated with steroids was impressively lower in patients receiving a low steroid dose.
TL;DR: A comparison of the haematological and haemoglobin synthesis findings of individuals with normal α genotypes with those with one (‐ α/αα) or two (‐α/‐α) α genes deleted shows that the latter two groups have more balanced globin chain synthesis ratios, higher ha Hemoglobin levels, and larger, better haemobicized red cells.
Abstract: The alpha globin genotypes of 55 beta thalassaemia heterozygotes have been determined by restriction endonuclease analysis to identify those with interacting alpha thalassaemia genes. A comparison of the haematological and haemoglobin synthesis findings of individuals with normal alpha genotypes (alpha alpha/alpha alpha) with those with one (-alpha/alpha alpha) or two (-alpha/-alpha) alpha genes deleted shows that the latter two groups have more balanced globin chain synthesis ratios, higher haemoglobin levels, and larger, better haemoglobinized red cells. This suggests that the degree of globin chain imbalance is a significant factor in determining the red cell characteristics in heterozygous beta thalassaemia. Screening programmes for thalassaemia, based on the detection of low MCVs, could miss cases of the interaction of alpha and beta thalassaemia.
TL;DR: The data suggest that αCS mRNA is unstable and degraded in the cytoplasm and may be due to destabilization of a specific sequence in the 3’non‐coding region during translation.
Abstract: Haemoglobin Constant Spring (Hb CS) is a variant with an elongated alpha-chain associated with an alpha + thalassaemia phenotype. The amount of alpha mRNA relative to beta mRNA in reticulocytes was reduced in carriers of Hb CS by an amount equivalent to the reduction observed in carriers of alpha + thalassaemia. In a patient with Hb CS-H disease there was greater alpha/beta mRNA ratio in bone marrow nuclear RNA than in the peripheral blood. Furthermore, all the alpha mRNA in the patient's peripheral blood was derived from the alpha 1 (alpha A) gene. The data suggest that alpha CS mRNA is unstable and degraded in the cytoplasm. This instability may be due to destabilization of a specific sequence in the 3' non-coding region during translation.
TL;DR: The defects in two cases of hereditary persistence of fetal hemoglobin were localized by demonstrating a tight genetic linkage between the disorders and polymorphic restriction endonuclease sites within the beta-like globin gene complex.
Abstract: Nondeletion forms of hereditary persistence of fetal hemoglobin may result from regulatory disorders of globin gene expression. The defects in two such conditions were localized by demonstrating a tight genetic linkage between the disorders and polymorphic restriction endonuclease sites within the beta-like globin gene complex. In one instance, the defect probably occurred outside the region of DNA between the epsilon- and beta-globin genes.
TL;DR: Fourteen recirculating cooling water systems were surveyed during the summer, 1981, to see what factors might influence the prevalence of Legionella pneumophila and an association was found between the presence of the organism and the concentration of dissolved solids, and chlorides and the pH.
Abstract: Fourteen recirculating cooling water systems were surveyed during the summer, 1981, to see what factors might influence the prevalence of Legionella pneumophila. The effect on the organism of three anti-microbials was studied, each in two systems, by intermittent treatment at two week intervals. L. pneumophila was isolated from six of the 14 cooling systems at the beginning of the trial but by the end was present in ten. An association was found between the presence of the organism and the concentration of dissolved solids, and chlorides and the pH. There also appeared to be associations with exclusion of light and higher water temperatures. Repeated tests on eight untreated systems showed that two were consistently infected, three became and remained infected, one was infected on a single occasion and two were never infected with L. pneumophila. Treatment of a contaminated system, either with a 10 p.p.m mixture of a quaternary ammonium compound and tributyltinoxide or slow release chlorine briquettes (maximum recorded free chlorine level 1.2 p.p.m.), did not eliminated legionellae. Treatment of two infected towers with a chlorinated phenol (100 p.p.m.) eliminated legionellae for at least three days, but after 14 days the organism was again found.
TL;DR: The results suggest that human milk can be effectively pasteurised using less heat treatment than in classical holder pasteurisation and preserves substantially more of the activity of the antimicrobial proteins present in human milk.
TL;DR: The results suggest that the acute transformation of CML cannot be simply explained by clonal changes and that environmental and regulatory factors could be also involved.
Abstract: Megakaryocyte (MK) colony formation has been studied in the chronic phase and in the blast crisis of chronic myeloid leukaemia (CML). Blood cells were grown in plasma clot for 13 d. MKs were subsequently identified by immunofluorescent techniques using two monoclonal antiplatelet antibodies (AN51 and J15). The maturation process was studied by ultrastructural methods. A marked increase in the number of circulating CFU-MK was observed in all the 10 cases studied prior to chemotherapy (70-fold increase per ml of blood). No significant modification in the regulation of MK colony formation as compared to that of normal subjects was observed. The predominant abnormality in maturation in culture was the occurrence of many hypoploid MKs (microMKs). However, the cytoplasmic maturation of the MKs was identical to that of normal subjects with occasional platelet shedding. Since microMKs predominated in some patients, scoring of MK colonies in CML necessitated immunofluorescent labelling to permit identification of MKs. During the blast crisis, MK colony formation occurred in four out of five patients with an extremely high plating efficiency in the case of promegakaryoblastic transformation. In contrast, MK colonies could not be grown from blood samples of patients with acute leukaemia, including two cases of promegakaryoblastic leukaemia. Maturation of MKs in blast crisis was identical to that of the chronic phase. Furthermore, after short periods of culture in liquid medium, circulating promegakaryoblasts from spontaneously to become large MKs exhibiting demarcation membranes and α-granules, while those from two cases of megakaryoblastic leukaemias did not mature. In consequence, the blast crisis of CML exhibits a different culture pattern from acute leukaemia. These results suggest, therefore, that the acute transformation of CML cannot be simply explained by clonal changes and that environmental and regulatory factors could be also involved.
TL;DR: The HB F levels in SS disease were significantly correlated with parental Hb F levels, suggesting that genetic factors regulating adult HbF levels are active at earlier stages in development.
Abstract: The decline of fetal haemoglobin (Hb F) from birth to 6 years has been compared in a cohort of 266 Jamaican children with homozygous sickle cel (SS) disease and in 243 matched controls with a normal haemoglobin (AA) genotype. Hb F levels were significantly higher in the SS cases from 1 month onward but, unlike the normal controls, no sex difference was apparent. The Hb F levels in SS disease were significantly correlated with parental Hb F levels, suggesting that genetic factors regulating adult Hb F levels are active at earlier stages in development. Furthermore, some of these genetic determinants of Hb F production may be linked to the beta-like globin gene complex and be in linkage disequilibrium with the beta s allele.
TL;DR: Findings indicate that a positive IgG DAT in malaria does not necessarily lead to excess haemolysis of non-parasitized red cells and indicates a relationship between the development of the positive DAT and acquisition of protective malarial immunity.
Abstract: The direct antiglobulin test (DAT) was performed on 134 Gambian children with P. falciparum malaria. 52 children had a positive DAT and in 25 this was due to the adherence of C3 to their red cells whilst 13 had sensitization with IgG as well as C3. Sensitization with C4 alone or associated with IgG and/or C3 was only rarely found. The haemoglobin levels and reticulocyte counts were not significantly different in patients with a positive DAT from those with a negative DAT. The children with positive IgG DAT, however, were of a significantly older age group and had significantly higher parasitaemias at presentation than children with complement components only or with a negative DAT. In vitro assay of phagocytosis by peripheral blood monocytes (PBM) showed that PBM from malarious patients were less active in phagocytosis than normal male adult Caucasian PBM. Neither PBM from malarious patients nor normal adult Caucasians PBM showed phagocytosis of cells from DAT positive malarious children. The same in vitro assay was used to test for the presence of opsonizing anti-schizont antibodies in the sera of these children and in adult Gambians. This revealed the presence of a schizont specific opsonizing antibody in the sera of adult Gambians and in the sera of children with a positive DAT due to IgG but not in sera of patients with a negative IgG. These findings indicate that a positive IgG DAT in malaria does not necessarily lead to excess haemolysis of non-parasitized red cells. The presence of a schizont opsonizing antibody, leading to in vitro phagocytosis, in the sera of children with a positive DAT and in sera from adult Gambians indicates a relationship between the development of the positive DAT and acquisition of protective malarial immunity.
TL;DR: The results of a reciprocal nursing experiment suggest that the typical rate of milk transfer is a product of both milk release by the mother and milk demand by the baby.