Congenital hypothyroidism with spuriously increased FT3 concentrations in infant and mother.
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Biomedical subjects
Publications and source records attributed to R Hall.
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Two patients with situs inversus and biliary atresia were treated with hepatic transplantation, one with an auxiliary liver and the other with an orthotopic graft which was placed using a piggy-back technique. Both transplants functioned well initially. The auxiliary liver was rejected after 1 1/2 months, and the patient died after an attempt at retransplantation many months later. The recipient of the orthotopic liver has perfect liver function 10 months postoperatively.
We have treated 16 acromegalic patients for up to 44 months with octreotide in varying doses. Growth hormone levels were suppressed in 14 patients with associated clinical improvement. IGF-1 levels were measured in 12 and fell into the normal range in 10. Prolactin was suppressed in six hyperprolactinaemic patients but was unaltered in normoprolactinaemic acromegalic patients. Post-prandial hyperglycaemia with impaired insulin secretion was noted in all patients, and one patient required oral hypoglycaemic agents. Octreotide did not affect thyroid function. CT scans from before and after six months of treatment demonstrated minimal tumour shrinkage in only two patients. Octreotide was well tolerated with no serious haematological or biochemical disturbance and no evidence of malabsorption. Two patients developed gallstones. Octreotide is effective in acromegaly. The development of gallstones is the only serious adverse event we have encountered.
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We describe the characterisation of polypeptides located on the surface of Theileria annulata sporozoites, macroschizonts, piroplasms and infected lymphoblastoid cells using surface iodination techniques. The sporozoite stage exhibited a complex profile of surface polypeptides. However, using data from experiments with defined monoclonal antibodies, the sporozoite surface appeared to be composed of several distinct groups of related polypeptides. Analysis of the macroschizont detected seven surface polypeptides, while eight polypeptides were identified for the piroplasm stage. On the basis of molecular weight comparisons, one of the surface polypeptides appeared to be common to the sporozoite, macroschizont and piroplasm. Stage cross-reactive monoclonals failed to immunoprecipitate a surface-radiolabelled polypeptide, and this prohibited the characterisation of a stage common surface antigen. From the surface labelling studies of Theileria-infected and uninfected lymphoblastoid cell lines, we concluded that infection results in major changes at the surface of the host cell, including both the appearance and loss of specific polypeptides. By employing monoclonal antibodies which detect infection-associated determinants, and a polyclonal antiserum raised against a glycoprotein fraction of an infected cell lysate, surface-labelled polypeptides were specifically immunoprecipitated from extracts of infected cells. The polypeptide detected by monoclonal antibody 4H5 was characterised as an infection-associated glycoprotein which varies in molecular mass when immunoprecipitated from different infected cell lines. The identification of infection-associated glycoproteins on the surface of the lymphoblastoid cell suggests that these molecules may be recognised by the cytotoxic T cells of immune animals.
A library consisting of randomly sheared Theileria annulata genomic DNA fragments in the vector lambda gt11 was screened with a Drosophila DNA segment containing the coding region of the 70-kDa heat-shock protein (hsp) gene. A positive recombinant was isolated and subjected to nucleotide sequence analysis. The DNA segment contains an open reading frame coding for a 71-kDa protein strongly homologous to hsp 70 from other organisms. Using this DNA as a probe, a homologous 2.5-kb RNA species was detected in sporozoites, piroplasms and a macroschizont-infected cell line, showing that this gene is constitutively expressed. The amount of this RNA increased following heat shock in the macroschizont-infected cell line. The T. annulata genome contains other sequences that hybridize weakly with this heat-shock gene.
Theileria annulata is an economically important protozoan parasite that threatens an estimated 250 million cattle with the disease tropical theileriosis. Development of a defined subunit vaccine is one means of trying to develop control measures against the disease. To this end we have characterized a surface antigen complex of the infective stage (sporozoite), by using a monoclonal antibody that neutralizes sporozoite infectivity in vitro. We have cloned the gene coding for this complex and have demonstrated that a fusion protein expressed from a fragment of this gene elicits strong neutralizing antibodies. Furthermore we provide data on the structure and expression of this gene. In particular we show that the region of the gene, expressed in one clone, codes for a protein segment relatively rich in proline residues. Also we demonstrate that expression of this gene appears to be stage specific, transcripts being present only in the sporoblast and sporozoite stages. The relevance of these findings to the production of a defined subunit vaccine is discussed.
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A primary standard for the assay of thyroid autoantibody subclass distribution was prepared by removing all but one IgG subclass from a standard serum by negative affinity chromatography. Affinity columns were prepared using murine monoclonal antibodies showing restricted specificity for human IgG (clone TM10-non-IgG1; HP6019-non-IgG2; VC9-nonIgG3 and 1a1-non-IgG4). Aliquots of patient serum were chromatographed and the eluted fractions assayed for IgG subclass concentration and thyroid autoantibody activity by ELISA. Recoveries of the desired IgG subclasses were: TM10 26.7%, HP6019 77.3%, VC9 53.0% and 1a1 46.0%. Contamination with unwanted subclasses was usually less than 1% but there was some "breakthrough" of 3 and 4 with HP6019. The thyroid autoantibody distribution, corrected for recovery and dilution, was thyroglobulin autoantibody (TgAb) IgG1 61.2%, IgG2 37.7%, IgG3 2.7%, IgG4 2.9% and thyroid microsomal autoantibody (MicAb) IgG1 73.7%, IgG2 19.8% IgG3 3.6% IgG4 3.8%. Several other serum samples were also analyzed by this technique and also by subclass ELISA calibrated with this standard serum. Regression analysis of the data obtained by the two assay methods gave correlation coefficients of r = 0.88 for TgAb and r = 0.82 for MicAb.
Pulmonary angiography remains the definitive technique for the diagnosis of pulmonary embolism but in practice is not universally available. Many patients can be managed quite safely without it but it should be employed without hesitation in certain problem patients. Thrombolytic treatment probably improves survival in patients who suffer an acute massive pulmonary embolus but it should not be used unless the embolus causes considerable haemodynamic disturbance. The best thrombolytic agent and the best administration regime remain uncertain. At present the simplest and cheapest effective regime for most patients is provided by a twelve to 24 hour infusion of streptokinase although in the future the new "clot-specific" agents such as rTPA and APSAC may be shown to be safer and/or more effective. In nearly all situations other than acute massive pulmonary embolism thrombolytic treatment is more expensive, slightly more dangerous but no more effective than heparin. When heparin is given there seems little to choose between intermittent injection and continuous infusion. Although there is no scientific proof it is logical to continue heparin for seven days since this is the time taken for any residual clot in the venous system to become firmly adherent to the vessel wall. The value of coagulation tests as a guide to adjustment of heparin dosage is not proved and seems to need reassessment in the light of the recent discovery of large diurnal variations in heparin activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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Results of prothrombin time tests for the control of oral anticoagulant therapy, when using automated blood coagulation instruments (coagulometers), may not be the same as those obtained when using manual methods, and variation in coagulometer performance may affect clinical interpretation of data. The haematology advisory committee of the Institute of Medical Laboratory Sciences has recommended that coagulometers should be used for determination of prothrombin times only if it can be demonstrated that the results are valid when compared with those of a standardised manual method. A protocol for the evaluation of coagulometers, and details of the procedures, are given in this report, the main emphasis of which is on the assessment of instruments for determination of the International Normalised Ratio. Guidelines are also provided for the general use of machines of this type and for the assessment of safety. The principles of the protocol are applicable to other automated tests of blood coagulation.
Gross nuclear morphology is a major diagnostic feature in the identification of subtypes of non-Hodgkin's lymphoma (NHL). The authors have shown that the size, shape, and chromatin distribution of the lymphocyte nuclei vary extensively both within and between samples of a subtype, and have proposed that the variations may reflect qualitative and quantitative differences in extrachromatinic components. To test this hypothesis, the organization of individual nuclear antigens in NHL and in reactive hyperplasia biopsies was examined by immunofluorescence labeling of frozen sections with previously characterized monoclonal antibodies. The results have been correlated with observations of the staining patterns produced by the antibodies in mitogenically stimulated human peripheral blood lymphocytes. Labeling pattern and intensity with each antibody were consistent between preparations of blood lymphocytes, and all four antibodies labeled all blood lymphocyte samples tested. In contrast, only 15% of the 53 biopsies were labeled by all four antibodies, although all were stained by anti-peripherin, nearly 80% by I1, and almost 60% by PI1. Antibody PI2 labeling was detected in only 20% of the samples. Variation in labeling intensity was equally extensive both within and between biopsy samples. In general, there was little homogeneity between samples of an NHL subtype as to which antigens were detected, their labeling intensity, or their pattern of intranuclear distribution. These observations are consistent with earlier reports of significant diversity in the morphology of nonchromatin components in such samples. The data support the proposition that the heterogeneity of gross nuclear morphology in nuclei of NHL biopsies may be due in part to disordered expression or abnormal organization of nuclear proteins.
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A high prevalence of postpartum thyroid dysfunction has been reported in several countries, but there have been no systematic studies of its prevalence in Britain. Among a group of 901 consecutive, unselected pregnant women thyroid autoantibodies were detected in 117 (13%) at booking. The clinical course of postpartum thyroid dysfunction, factors associated with its development, and its likely prevalence were defined in 100 of these women with thyroid antibodies and 120 women with no such antibodies who were matched for age. None of the women had a history of autoimmune thyroid disease. Normal reference ranges for thyroid function during pregnancy and post partum were established in the 120 women negative for thyroid antibodies. On the basis of these observations postpartum thyroid dysfunction was observed in 49 (22%) of the 220 women studied, and the prevalence in the total group of 901 women was estimated to be 16.7%. Thyroid dysfunction, mainly occurring in the first six months post partum, was usually transient and included both destruction induced hyperthyroidism and hypothyroidism. The development of the syndrome was significantly related to smoking more than 20 cigarettes a day and the presence of thyroid microsomal autoantibodies at booking. Of the 16 women with a family history of thyroid disease in whom thyroid microsomal autoantibody activity was detectable at booking, 11 developed thyroid dysfunction. Age, parity, presence of goitre at presentation, duration of breast feeding, and the sex and birth weight of the infant were not associated with the development of postpartum thyroid dysfunction. The mood changes experienced by women post partum may in part be associated with altered thyroid function during this time.
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