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Biomedical subjects

N T James

Publications and source records attributed to N T James.

At least 37 records · Page 2Linked to original sources

Abnormal macrophage development in Hodgkin's disease: a morphometric study.

The development of macrophages from blood monocytes from 22 patients with untreated Hodgkin's disease and 20 normal subjects has been studied at intervals over a 6-day period of suspension culture in the presence of autologous serum and lymphocytes. Morphometric measurements were made on electron micrographs and the results subjected to multivariate and univariate analyses of variance. The cells from the Hodgkin's group showed highly significant differences from normal. The whole-cell volume, surface area, and cell membrane excess, as well as the mitochondrial volume and surface area, showed smaller increases over the period of culture, and the normal increase in mitochondrial profile numbers was not seen. It would appear that although the patients' monocytes transformed into macrophages in culture, their development was seriously deranged.

Adult↗

Ultrastructural features of acute monoblastic leukaemia cells: a multivariate morphometric analysis.

Morphometric studies were carried out on five ultrastructural measures of size or quantity of some of the intracellular organelles in monoblasts obtained from six patients diagnosed as having acute monoblastic leukaemia and also on monocytes from six normal controls. The morphometric measures were analysed using a one way multivariate analysis of variance (MANOVA) to see whether acute monoblastic leukaemic cells differed from those of normals. It was found that there was a highly significant decrease both in the surface to volume ratio of mitochondria and also in the surface to volume ratio of the nucleus. The possible physiological significance of these structural changes is stressed.

Adult↗

Disordered development of macrophages in non-Hodgkin's lymphoma.

Macrophage development in 20 untreated patients with non-Hodgkin's lymphoma (NHL) has been studied and compared with that in 20 normal subjects. Morphometric measurements were carried out on ultrastructural features of cell, nucleus and mitochondria during 6 days suspension culture of blood monocytes in the presence of autologous serum and lymphocytes. The results were subjected to multivariate and univariate analysis of variance. Statistically significant differences were found between the subject groups with respect to the volumes and surface areas of cell, nucleus and mitochondria, to the excess surface membrane of cell and nucleus (as compared with equivalent spheres) and to the number of mitochondrial profiles per section. It would appear that the patients' cell grew less, showed less elaboration of surface features and had reduced nuclear and mitochondrial development, the latter affecting mitochondrial numbers rather than individual size. The findings provide further evidence that mononuclear phagocytes are deranged in NHL.

Adult↗

Hypereosinophilic syndrome: case report and morphometric study.

A clinical study of a patient with hypereosinophilic syndrome is presented. The blood eosinophil count reached 273 x 10(9) cells per litre. There were only mild symptoms but skin, lung and heart were affected. There was a good response to treatment. In a morphometric analysis, the patient's eosinophils were compared with those of 9 healthy subjects, using appropriate multiple comparison procedures. The patient's eosinophils showed significantly increased cell size and surface area. Mitochondrial volume and surface area were also increased and there were more mitochondrial profiles per section. The eosinophil granules showed a striking reduction in total volume, both the number of profiles and the profile area of individual granules being decreased. These findings are consistent with inappropriate activation and degranulation, a relatively orderly degranulation perhaps accounting for the mild symptoms. This investigation illustrates the value of morphometry in quantitating cellular changes in haematological disorders.

Adult↗

Morphometry of human blood leukocyte ultrastructure: its potential value in haematology.

A review of the literature on ultrastructural morphometry of human blood leukocytes has been carried out. It is concluded that: (1) Blood leukocytes are particularly suitable for morphometric study. (2) Morphometric methods have proved valuable in defining differing cytological features of cells in various lymphoid malignancies, and in demonstrating ultrastructural differences (which could not otherwise have been detected) in monocytes and eosinophils corresponding to known functional changes. (3) Appropriate and valid numerical procedures are essential for determining morphometric equations and statistical probabilities; both morphometric measurement and statistical analysis are made easier by the use of computers. (4) Ultrastructural morphometry should ultimately find an important place in clinical haematology.

Hematologic Tests↗

Morphometry of eosinophils in human blood.

Ultrastructural characteristics of human blood eosinophils have been analysed by morphometric methods in 18 healthy adults. Data were obtained relating to whole cell, nucleus, mitochondria and specific granules. No significant differences were found between the eosinophils of the 9 male and 9 female subjects. The results provide normal values against which changes in eosinophils in disease states may be assessed.

Adult↗

Human macrophage development: a morphometric study.

The development of macrophages from the blood monocytes of ten normal subjects has been studied at intervals over a six day period. Suspension cultures were used to obtain randomly orientated cells and morphometric measurements were made on electron micrographs. In order to meet the requirements for normality of distribution and homoscedasticity, data were logarithmically transformed. A two-way analysis of variance was then carried out, taking subjects and time intervals as fixed effects, and using a least significant difference procedure to detect variations between culture time intervals. The whole cell and cytoplasmic volumes showed 3-4 fold increases during culture. The cell surface area more than doubled; this was partly attributable to the larger cell volume and partly to increased surface irregularity. The mitochondrial volume also showed a similar significant increase, attributable to an increase in both number and size of mitochondrial profiles, the cytoplasmic volume fraction remaining approximately constant. Although there was a statistically significant increase in nuclear surface area, the nuclear changes were relatively small. The results and the application of appropriate statistical methods have thus provided basic morphometric data for human macrophage development in culture. The experimental system should permit further investigation of factors governing impaired macrophage development in malignant disease.

Adult↗

Quantitative studies on the nuclei of muscle of congenitally dystrophic mice.

Stereological analyses of the pattern of distribution of heterochromatin and euchromatin in nuclei of muscle fibres are reported. Patterns of distribution found in myonuclei from extensor digitorum longus muscle of C57BL/6Jdy2J/dy2J dystrophic mice were compared with those found in myonuclei from the same muscle of clinically unaffected littermates and of normal control mice. Using a well-known spatial pattern analysis technique, clear differences between these types of nuclei were found. Such differences are clearly of value in helping our understanding of the pathological processes occurring in dystrophic muscle, and may be relevant to future identification and diagnosis of abnormal muscle.

Animals↗

Morphometry of blood monocytes in malignant lymphoma.

Morphometric methods were used to study the ultrastructure of blood monocytes in 23 patients with Hodgkin's disease, 12 patients with non-Hodgkin's lymphoma, and 20 normal subjects. The results were analysed using both univariate and multivariate methods. Both analyses supported the interpretation that the total mitochondrial contribution to the cellular ultrastructure was less in Hodgkin's disease than in the other two groups, with smaller mitochondrial volume fractions, volumes, and surface areas being found. In the patients with non-Hodgkin's lymphoma univariate analysis suggested that monocyte nuclei were larger, with more euchromatin and a relatively smaller heterochromatin-euchromatin interface; the cell profile area was larger and the surface to volume ratio was smaller compared with normal subjects. Morphological changes have not previously been described in blood monocytes in malignant lymphoma, but they may be the counterpart of the known mononuclear phagocyte dysfunction.

Adolescent↗

Morphometry of monocytes of human blood.

Morphometric methods have been used to analyse the ultrastructural characteristics of human blood monocytes in 20 normal adults. Data were obtained relating to whole cell, nucleus and mitochondria and, using a method not previously applied to blood cells, for the distribution of heterochromatin and euchromatin. The results provide a normal baseline against which monocyte changes in disease can be assessed.

Adolescent↗

Morphometric analyses on the muscles of exercise trained and untrained dogs.

Nine adult dogs were subjected to an endurance training program consisting of gradually increasing periods of treadmill exercise. Biopsies of vastus lateralis muscles taken prior to an on completion of the training program were used to study the alterations in the capillary network and muscle-fiber nuclei. Combined morphometric and stereological analyses showed that the total length of capillaries (LV) and their total surface area (SV) per unit volume of muscle was significantly increased during training. Changes in the properties of myonuclei following training were also studied. Highly significant increases in the number of nuclei per unit volume of muscle (NV) were found. The increase in the numerical density of muscle-fiber nuclei would seem to indicate that the new nuclei were formed in the muscle during prolonged training. The relative amounts and distribution of heterochromatin and euchromatin were measured in trained and untrained dogs using a simple point-counting and random-transect technique. Their content of the different types of chromatin (volume functions and chromatin patch sizes in micrographs) were found to be altered significantly as a result of the training. The findings were consistent with the view that the amount of euchromatin within nuclei varies according to the degree of cellular activity.

Adaptation, Physiological↗

Stereological analyses of capillaries in muscles of dystrophic mice.

Stereological analyses of the distribution of capillaries in skeletal muscles of congenitally dystrophic mice are described and reported. Two methods are used, each based on a different mathematical model of the 3-dimensional distribution of lines in space. For these analyses specimens of extensor digitorum longus muscle from clinically affected C57BL/6Jdy2J/dy2J dystrophic mice, and from non-littermate controls, were used. The analyses were carried out on transverse and longitudinally orientated semithin sections of these muscles. Although the two methods employed are based on different mathematical models and yield results relevant to each particular model, it is clear that there is a more extensive capillary network present per unit volume of the dystrophic muscle than in control muscles. These findings are relevant to the theories which involve a vascular aetiology for muscular dystrophy. It is apparent that, in order to explore the structure of the capillary network more fully, there is a need for the development of more sophisticated stereological techniques for analysis of capillaries in skeletal muscle.

Animals↗

A stereological analysis of capillaries in normal and hypertrophic muscle.

A realistic model of the distribution of the partially orientated capillaries in skeletal muscles has been introduced for stereological analyses. Distributional parameters not previously estimated for capillary networks in muscles have been quantified. These include the lengths of capillary per unit volume of tissue ((L(v)) and a dimensionless index of orientation (omega). The present study demonstrates that surgical techniques for inducing skeletal muscle hypertrophy can be an effective stimulus for the proliferation of additional capillaries. In the hypertrophic muscles studied the capillaries become more highly orientated. This suggests that the growth of new capillaries occurs preferentially along the long axis of the muscle.

Animals↗

Quantitative studies on the numerical frequency of myonuclei in the muscles of exercised rats: evidence against the occurrence of fibre-splitting.

The histological changes associated with exercise-induced muscular hypertrophy have variously been interpreted as due to fibre-splitting or satellite-cell activity. If due to fibre-splitting, than a marked fall in the number of nuclei per unit volume of muscle must occur. To see if this is the case, we have examined post-mortem specimens of extensor digitorum longus muscles in rats exercised by swimming for up to 30 min twice daily for 35 days. The mean cross-sectional area of muscle fibres was unaltered by exercise but mean length of capillary per unit volume of muscle was increased by 55% and number of nuclei per unit volume of muscle by 30%, both changes being significant. Mean nuclear volume increased by approximately 75%. Thus the muscles did adapt to exercise and new myonuclei were formed, contrary to expectations if fibre-splitting were the essential change. In this study the fibres seemed not to have increased in size and further studies, perhaps using autoradiographic analysis of tritiated thymidine-labelled satellite-cell nuclei, are needed to clarify the precise mechanisms involved.

Animals↗

Stereological analysis of the number of nuclei in skeletal muscle fibres.

A simple morphological method is described whereby the numbers of nuclei in different types of skeletal muscle fibre may be determined. The method allows for the anisotropy of skeletal muscle fibres and the non-random distribution of their nuclei. The advantages in the use of a morphological (rather than a biochemical) method are discussed, together with possible applications of the method in the study of changes which occur in skeletal muscle in adaptation to stress and in disease.

Animals↗