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Biomedical subjects

M Hughes

Publications and source records attributed to M Hughes.

At least 217 records · Page 12Linked to original sources

Morphology and kinetics of erythropoiesis in haemoglobin H disease.

Some aspects of erythroblast function have been investigated in two Thai patients with haemoglobin H disease. Electron microscope and high resolution autoradiographic studies revealed that (1) some erythroblasts and marrow reticulocytes contained branching intracytoplasmic inclusions and (2) the presence of such inclusions did not necessarily prevent the entry of cells either from the G1 phase into the S phase or from the G2 phase into mitosis. The distribution of early polychromatic erythroblasts in the different stages of the cell cycle was determined by the technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography and found to be essentially normal. It is concluded that although the presence of an excess of alpha-chains in the beta-thalassaemia syndromes has been previously shown to be associated with a gross impairment of erythroblast proliferation, the presence of an excess beta-chains in HbH disease is not.

Adult↗

Ultrastructure of red cells containing haemoglobin H inclusions induced by redox dyes.

Electron microscope studies have been performed to investigate the ultrastructural basis of the characteristic golf-ball-like light microscope appearance which develops when the erythrocytes of patients with HbH disease are stained supravitally with brilliant cresyl blue or new methylene blue. The data indicate that the golf-ball appearance resulted from the formation of many spherical or biconvex masses of electron-dense material which were attached to and which bulged the cell membrane. These masses presumably consisted of denatured HbH. A variable proportion of the red cells of the four patients investigated failed to form such membrane-associated inclusions even after treatment with redox dyes for 24 h. Studies of subpopulations of red cells which were separated according to cell age suggested that there was a considerable variation in the HbH content of young red cells and indicated that with increasing cell age there is an increase in the proportion of red cells which do not contain appreciable quantities of HbH.

Coloring Agents↗

Prevalence of high (3S)-3-hydroxyquinidine/quinidine ratios in serum, and clearance of quinidine in cardiac patients with age.

In the sera from 42 patients receiving quinidine, (3S)-3-hydroxyquinidine (3-OH), an active metabolite of quinidine, and quinidine were determined by high-pressure liquid chromatography with fluorescence detection. These results were added to those of 25 other patients reported previously. The 3-OH/quinidine ratio averaged 0.34 +/- 0.17 (SD) with a range of 0.10 to 0.90. Eleven patients (16%) had ratios above 0.50. After adjusting for protein binding differences between the 2 compounds, these 16% had 3-OH concentrations in serum water greater than that of quinidine. An additional 7 patients (10%) of the total) had levels of this metabolite in serum water slightly less than that of quinidine. A histogram showing the frequency distribution of 3-OH/quinidine in serum indicates extensive skewing with possibly a bimodal distribution with the antimode at 0.50. Thus, 3-OH may make a significant contribution to the effect of quinidine therapy in a fraction of treated patients. The clearance of quinidine decreased with age, indicating the need for, on the average, higher doses of quinidine in the young.

Adult↗

The anaemia of P. falciparum malaria.

The haematological changes in a group of young Gambian children with P. falciparum malaria have been analysed. In children with acute infection anaemia was most marked during the period after treatment. Although many of these patients developed a positive direct Coombs test during this period of the illness it is not clear whether the anaemia which occurs after treatment has an immune basis. A second group of children showed quite different haematological findings. They appear to have a more chronic form of P. falciparum malaria infection, were profoundly anaemic at presentation, showed gross dyserythropoietic changes in their bone marrows, and had a full reticulocyte response and rise in haemoglobin after treatment. A third group of children were encountered whose haematological abnormalities were intermediate to those of the acute and chronic groups. These findings indicate that the patho-physiological mechanisms responsible for the anaemia of P. falciparum malaria are different at different stages of the illness.

Anemia↗

Ultrastructural studies of erythropoiesis in beta-thalassaemia trait.

The erythropoietic cells of six cases of beta-thalassaemia trait were studied by electron microscopy and electron microscope autoradiography. Intracytoplasmic and intranuclear alpha-chain precipitates were found in some late polychromatic erythroblasts and intracytoplasmic precipitates were found in several marrow reticulocytes. This provides direct morphological evidence of unbalanced globin chain synthesis in the marrow. Several of the polychromatic erythroblasts and marrow reticulocytes contained autophagic vacuoles and showed a variety of other dyserythropoietic changes. Erythroblast profiles containing moderate quantities of precipitated alpha-chains usually suffered from a marked depression of protein synthesis. The proportions of marrow cells containing alpha-chain precipitates and displaying dyserythropoietic changes varied considerably from patient to patient. It is proposed that this variation largely reflects variations in the proteolytic capacity of the erythropoietic cells in different individuals and leads to different degrees of ineffective erythropoiesis in beta-thalassaemia trait.

Adult↗

Electron microscope and high resolution autoradiographic studies of the erythroblasts in haemoglobin H disease.

Electron microscope studies of bone marrow from a patient with haemoglobin H (HbH) disease have revealed the presence of highly condensed branching intracytoplasmic inclusions within a proportion of the early and late polychromatic erythroblasts and reticulocytes. Intraerythroblastic inclusions of this type have not yet been described in any other haematological disorder and may well be a specific feature of HbH disease. Electron microscope autoradiographic studies of the marrow cells from the patient with HbH disease revealed that (1) active protein synthesis continues in inclusion-containing erythroblasts and (2) there is a rapid precipitation of a considerable proportion of the newly synthesized free beta chains onto the surfaces of preformed inclusions, presumably after conversion to HbH. These electron microscope and electron microscope autoradiographic findings are quite different from the findings previously reported in homozygous beta thalassaemia using the same techniques.

Autoradiography↗

Can alphabet recall be part of a visuo-spatial task?

Fifty male and 50 female undergraduates were subjects in an experiment where they were required to recall the alphabet and to count either the number of letters containing the sound 'ee' or the number of letters with curves in the upper-case form. The results fail to replicate those of Coltheart et al. (1975), but are consistent with current models of hemispheric specialization. Males were found to complete the visuo-spatial task slower than the females and it is argued that this is due to their greater degree of hemispheric specialization which necessitates transfer of information between hemispheres.

Adult↗

Evidence for an immunological relationship between Streptococcus mutans and human cardiac tissue.

Two-dimensional immunoelectrophoresis, indirect immunofluorescence, and radioimmunoassay were used to demonstrate that antisera from rabbits immunized with some strains of Streptococcus mutans contain antibodies that cross-react with human cardiac tissue. These rabbits were sensitized to a shocking dose of human heart antigen, and anaphylactic deaths were sometimes produced. Myocarditis was also a result of the immunization procedure. Data obtained with all five techniques were comparable. Cross-reactivity could be associated with three antigens designated ID, IF, and HL. Antigens ID and IF were major immunogens of S. mutans Ingbritt, but HL antibodies were produced only after hyperimmunization. Corss-reactivity was of an immunological nature and not the result of nonspecific factors such as bacterial Fc reactive components or antibody elicited to growth medium constituents. These findings support the hypothesis that immunization with S. mutans can induce autoimmune reactions and indicate that antigens must be selected with caution before formulating any dental caries vaccine.

Anaphylaxis↗

Radioimmunoassay of class-specific antibodies to Streptococcus mutans in monkey serum and saliva.

A radioimmunoassay (RIA) has been developed to measure class-specific antibodies to Steptococcus mutans in the serum and saliva of monkeys (Macaca fascicularis). Anti-human immunoglobulin antibodies purified by affinity chromatography on immobilised monkey immunoglobulins and labelled with 125I were employed. Formolised cells of S. mutans and an extract of culture supernatant adsorbed to polystyrene wells were used as solid-phase antigens. The coefficients of variation for IgG, IgA and IgM assays were less than or equal to 10% for both antigen systems. Two monkeys were immunised with formolised cells of S. mutans by subcutaneous injection and subsequent instillation of bacterial cells into their right parotid ducts. IgG, IgA and IgM antibody responses to S. mutans in samples of serum and saliva were quantitated by RIA. Immobilisation of purified components of S. mutans on polystyrene wells enabled the measurement of antibody response to a number of antigens to be made. The RIA is a sensitive, reproducible and quantitative method of measuring serum and salivary antibody responses in monkeys.

Adsorption↗

Heart-rate correlates of childhood activities: play, exploration, problem-solving and day-dreaming.

Heart-rate was monitored while children were engaged in different activities. The first study examined the hypothesis that the behavioural distinction between exploration and play would be supported by the psychophysiological measure. Two-year-olds showed suppression of heart rate variability (HRV) during exploration, and even more during solution of a puzzle, suggesting that the task demands these two activities were greater than those during play. The second study demonstrated a relationship between HRV during daydreaming and during problem solving in 9-year-old children which was similar to that obtained between play and problem solving in younger children. The correlative use of HRV thus strengthened functional interpretations of behaviour.

Child↗

Acromegaly due to production of a growth hormone releasing factor by a bronchial carcinoid tumor.

We have studied growth hormone production in a patient with a bronchial carcinoid and acromegaly. The absence of growth hormone from the carcinoid tumour was demonstrated by extraction, cell culture and immunoperosidase techniques. Using a linked perfusion culture system, effluent from the bronchial carcinoid tumour culture stimulated a rapid release of growth hormone from a rat pituitary monolayer. This is the first time evidence of growth hormone releasing activity by a bronchial carcinoid has been demonstrated in a production.

Acromegaly↗