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Biomedical subjects

G Hudson

Publications and source records attributed to G Hudson.

At least 55 records · Page 3Linked to original sources

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↗

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↗

Ultrastructure of skin window cells in malignant lymphoma.

The ultrastructure of cells in skin window preparations was analysed in 38 patients with malignant lymphoma and in 22 normal subjects. In the series as a whole, there were significant morphological changes in the macrophages between day 1 and day 2 consistent with cell maturation during the inflammatory response. At both intervals, lymphoma patients showed strikingly larger cell and nuclear profile areas as compared with normal subjects; there was a greater number of nucleoli per profile and proportionately more sections showed a Golgi complex. At day 1, a greater percentage of the patients' macrophages showed large numbers of phagocytic inclusions, but at day 2, significantly fewer profiles demonstrated this feature. These morphological findings could be a reflection of the known mononuclear phagocyte dysfunction in malignant lymphoma.

Adolescent↗

Ultrastructure of skin window cells in normal subjects.

Ultrastructural studies have been made of skin window inflammatory cells in 22 healthy human subjects at 24 hours and 48 hours after an initial abrasion. Large numbers of macrophages and neutrophil polymorphs were seen at both intervals. Compared with the 24 hours specimens, macrophages at 48 hours tended to have more eccentric and less irregular nuclei, as well as more voluminous cytoplasm; phagosomes and large vacuoles were much more prominent and cell diameters were larger. The differences are consistent with maturational changes in the macrophages during the inflammatory response. In the neutrophil polymorphs, the nuclei were frequently pycnotic and showed multiple profiles, and the complement of granules was small. Other cell types were only occasionally encountered. It is concluded that ultrastructural studies of skin window cells may have an application in investigating maturational defects of macrophages in malignant states.

Adolescent↗

Origin of crystalloid inclusions in macrophages I: studies of peritoneal macrophages after erythrocyte ingestion.

In an attempt to investigate the origin of crystalloid inclusions present in bone-marrow macrophages of normal adult mice and in man, murine peritoneal macrophages (which normally do not contain inclusions of this nature) were studied by light and electron microscopy 24 h after 3 daily injections of various preparations of erythrocytes. The preparations included mouse erythrocytes with and without pretreatment with collagenase, human erythrocytes and human-erythrocyte ghosts. Crystalloid inclusions were only rarely seen in the peritoneal macrophages in these circumstances. The results offered little support for the idea that crystalloid inclusions are derived from the breakdown of erythrocytes.

Animals↗

Origin of crystalloid inclusions in macrophages II: evidence for derivation from eosinophil granulocyte breakdown.

Peritoneal macrophages were studied by light and electron microscopy in normal adult mice 24 h after 3 daily injections of preparations of leucocytes and platelets. Crystalloid inclusions, similar to those seen in bone marrow macrophages of normal adult mice and in man, were occasionally observed in peritoneal macrophages after administration buffy-coat white cells but not after platelets. They were much more frequently seen following the ingestion of eosinophil-rich granulocytes and were almost always associated with secondary lysosomes. Energy-dispersive analysis of X-ray provided further evidence that both crystalloid inclusions and lysosomes originated from the injected granulocytes. These observations suggest that crystalloid inclusions in marrow macrophages are derived from granulocyte breakdown and that in this respect eosinophil granulocytes are of prime importance.

Animals↗

Skin window cellularity and macrophage changes in Hodgkin's and non-Hodgkin's lymphomas.

The cutaneous inflammatory response in patients with Hodgkin's and non-Hodgkin's lymphomas was investigated by light and scanning electron microscopy and compared with that of healthy subjects at 24 and 48 h. Both groups of patients showed a reduction in overall cellularity and statistically significant differences in macrophage surface morphology. In macrophages from healthy subjects, microvilli predominated but in lymphoma patients, cells with ruffles and/or ridges (resembling blood monocytes) were more frequent. In healthy subjects, the percentage of macrophages with predominant microvilli increased between day 1 and day 2. It is suggested that both the cellular response and the maturation (or activation) of macrophages are impaired in lymphomas.

Adolescent↗

Scanning electron microscopy of exudative macrophages in malignant lymphoma.

The possible value of scanning electron microscopy (SEM) of skin window preparations in the clinical situation has been investigated with reference to 48-hour macrophages in 26 patients with malignant lymphoma. The preparations were processed for SEM using critical point drying and sputter coating. Identification of macrophages was made with reference to light microscopy both of parallel preparations and of specimens already studied by SEM. Distinctive SEM appearances were present in most of the patients. Although many macrophages were similar to those from normal subjects, the majority showed a more variable morphology including the presence of ruffles and coarse ridge-like profiles. Highly significant differences were found on statistical analysis. It is suggested that immaturity of the 48-hour macrophages is present in some patients with malignant lymphoma (perhaps reflecting the macrophage dysfunction already described in these diseases). The findings indicate the potential clinical application for this technique.

Adult↗

Melanin granule in skin window macrophages.

Pigment granules have been studied in macrophages of skin window preparations. These granules usually appeared blue with Romanowsky stains, and stained positively for melanin but negatively for iron. There were significantly more pigment granules per macrophage in sun-tanned individuals and in coloured subjects and in the latter, the granules were usually larger and darker. Presumably, the source of the melanin is damaged or degenerating pigment cells of the skin and reflects a normal in vivo phenomenon.

Adolescent↗

Scanning electron microscopy of skin window cells of normal subjects.

With critical-point dried specimens, skin window cells of normal subjects showed a wealth of surface detail with no evidence of underlying nucleus or organells. Cells interpreted as neutrophils were characterized by delicate curved surface folds and variable numbers of fine filopodia; macrophages were larger and usually covered with tightly-packed clusters of knob-like microvilli, their periphery showing many filopodia and broader projections. Some macrophage filopodia took origin from the free surface of the cell and extended outwards to be attached to the coverslip for part of their extent, giving a 'fly-leg' appearance. Filopodial communications between cells were also present. With slow-dried preparations, the cells were flattened and a putative nuclear profile was evident. In these preparations quantitative analysis was made of various cell parameters comparing neutrophils and macrophages. The significance of these features has been discussed in relation to the in vivo inflammatory response as revealed by cell contact with a glass surface. The technique might be useful for studying haematogenous cells in certain disease states.

Adolescent↗

A simple technique for studying immunoglobulin synthesis by normal and malignant plasma cells in vitro.

Plasma cells from human marrows are saturated with C-14 labelled amino acids, harvested and recultured in unlabelled growth medium. The appearance of radioactivity in the growth medium then provides a simple and rapid measure of protein synthesis. The secreted radio-labelled material is characterized by isoelectric focusing and autoradiography in acrylamide gels, a technique which has advantages over established serological methods.

Autoradiography↗