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Biomedical subjects

G Hudson

Publications and source records attributed to G Hudson.

At least 19 recordsLinked to original sources
PubMed1992

Immune-mediated interactions during macrophage development in non-Hodgkin's lymphoma.

As part of an investigation of mononuclear phagocytes in malignant lymphoma, measurement of immune-mediated erythrophagocytosis and rosette formation was carried out on cells grown in suspension culture at the monocyte (Day 0) and macrophage (Day 6) stages; the culture medium contained autologous serum. Cells were derived from 10 patients with untreated non-Hodgkin's lymphoma (NHL) and from 12 normal individuals. The results were subjected to Analysis of Variance and demonstrated a significant difference between the two groups with respect to erythrophagocytosis but not to rosette formation. In the NHL group, the proportion of erythrophagocytic cells showed no significant increase between the monocyte and macrophage stages (0.07 to 0.09), in contrast to the marked increase seen in the normal group (0.09 to 0.24). In a pilot investigation to examine the possible role of factors in the serum, cells derived from the NHL patients were cultured with serum from healthy donors; they showed no significant difference in the immune-mediated functions from those grown in autologous serum. Overall, the results provide further quantitative evidence of defective macrophage maturation in NHL, presumably reflecting the compromise of host defence mechanisms.

Adult↗
PubMed1991

Ultrastructural morphometry of human leucocytes in health and disease.

In this review, the literature on ultrastructural morphometry of each of the main types of human blood leucocytes has been considered, together with the technical and numerical procedures essential for valid analysis. Quantitative data have been reported for these cell types in health and comparisons have been made with those in disease states. In monocytes, and in macrophages developing from them, subtle ultrastructural differences have been detected and quantitated in malignant lymphoma; as the mononuclear phagocytes were not themselves neoplastic, the changes may have related to defects in host defence. Change in the ultrastructural characteristics of leukaemic monoblasts have also been reported. Lymphocytes and malignant lymphoid cells have been extensively investigated: differences between different types and subsets have been shown to be present in both normal lymphocytes and their malignant counterparts in leukemias and lymphomas. Particular attention has been paid to morphometric assessment of nuclear shape and size in these disorders and to its possible value as a diagnostic tool. Granulocytes have so far been the subject of few morphometric studies, although in hypereosinophilic syndrome, cellular changes have been defined and have thrown light on the abnormal pattern of degranulation. There have also been scattered reports on the cells of acute myelogenous leukaemia. The use of computers and sophisticated statistical packages has greatly facilitated the application of multiple comparison procedures and has permitted discriminant analysis to be carried out where appropriate. This review shows that ultrastructural morphometry of leucocytes will have an increasing application in clinical pathology.

Granulocytes↗
PubMed1991

Changes in cellular dry mass during macrophage development.

Measurements of dry mass were made on developing human macrophages in suspension culture using a scanning and integrating microinterferometer. The mean dry mass (+/- SEM) of day 0 monocytes of 19 healthy individuals was 53.6 +/- 2.4 pg. There was a significant increase in cellular dry mass over the period of culture, mean values at 2, 4 and 6 days being 61.1, 79.8 and 110.4 pg, respectively. A comparison of the results with those obtained previously by ultrastructural morphometry inferred that there is a disproportionate increase in the water content of macrophages during development. The technique may have potential for investigating changes in mononuclear phagocytes in clinical states.

Adult↗
PubMed1991

Sequence of rat alpha 1-macroglobulin, a broad-range proteinase inhibitor from the alpha-macroglobulin-complement family.

The alpha-macroglobulin-complement family of plasma proteins includes at least three different alpha-macroglobulins in rats, alpha 2-macroglobulin (alpha 2M), alpha 1 inhibitor III (alpha 1I3), and alpha 1-macroglobulin (alpha 1M). These high molecular weight polypeptides (Mr 160,000 to 200,000) are broad-range proteinase inhibitors. They utilize an internal thiolester function to trap proteinases that cleave their bait regions. The amino acid sequences of alpha 2M and two variants of alpha 1I3 are known. The isolation of alpha 1M cDNA clones and the determination of their cDNA and derived amino acid sequences are reported here. Alpha 1M shares 57.2% and 53.0% overall amino acid sequence identity with alpha 2M and alpha 1I3, respectively, but differs significantly from both in its bait region, suggesting that each inhibitor addresses a different spectrum of proteinases. The disulfide bridge structure of alpha 1M was deduced from its sequence and showed extensive similarities with the experimentally determined structures of other alpha-macroglobulins, suggesting similar overall tertiary structures. Alpha 1M mRNA was detected in 13 different rat tissues tested, whereas alpha 2M and alpha 1I3 mRNAs showed a far more restricted tissue distribution. While alpha 2M and alpha 1I3 mRNA and protein concentrations are significantly altered during acute and chronic inflammations, alpha 1M plasma concentrations are changed only twofold. Thus, in contrast with alpha 2M and alpha 1I3, the functions provided by alpha 1M may be ubiquitously and constitutively required in a broad range of tissues.

Amino Acid Sequence↗
PubMed1991

Cellular dry mass during macrophage development in malignant lymphoma.

In order to throw light on known mononuclear phagocyte disturbances in malignant lymphoma, scanning and integrating microinterferometry was employed to measure dry mass in developing mononuclear phagocytes after 0, 2, 4 and 6 days of suspension culture, using cells from 19 healthy subjects, 19 patients with Hodgkin's disease and 17 with non-Hodgkin's lymphoma. Analysis of variance showed that highly significant increases in dry mass (approximately twofold) occurred over the six-day period. No significant differences were found between the subject groups, nor were any attributable to age or sex. In terms of their dry mass, mononuclear phagocytes from lymphoma patients undergo developmental changes in suspension culture that are similar to normal, but a comparison with earlier cell volume studies suggests that differences in cellular water content may be present.

Adult↗
PubMed1990

Morphometry of macrophage development in malignant lymphoma. Predictive value of discriminant analysis.

Discriminant analysis of morphometric data on the ultrastructure of developing macrophages has been used to classify 62 individual subjects into one of the 3 groups of origin, namely normal, Hodgkin's disease and non-Hodgkin's lymphoma, each finding being compared with the known diagnosis. The data had been obtained from blood monocytes grown in suspension culture over a period of 6 days, and related to whole cell, nucleus, nucleoli and mitochondria. Over 80% of subjects were correctly classified as between the 3 groups and over 90% as to their normality or otherwise. Although the non-specific nature of changes in defence cells makes it unlikely that morphometric studies of macrophages will find a place in the diagnosis of specific malignancies, the present work indicates it could be useful in assessing host response and hence prognosis and response to treatment. Discriminant analysis of quantitative differences in cell structure could have wide clinico-pathological application.

Adolescent↗
PubMed1990

Hepatic transcription of the acute-phase alpha 1-inhibitor III gene is controlled by a novel combination of cis-acting regulatory elements.

mRNA coding for the abundant broad-range plasma proteinase inhibitor alpha 1-inhibitor III (alpha 1I3) was detected only in rat liver, while mRNA for the related proteins alpha 1-macroglobulin and alpha 2-macroglobulin was also found in a variety of nonhepatic tissues. cis-Acting control elements necessary for the hepatic transcription of alpha 1I3 were mapped by transfection and expression studies of control-region constructs in cultured hepatic and nonhepatic cells. The promoter-proximal 5'-flanking region contained four control elements, I to IV, located between -109 and -196 base pairs upstream of the transcriptional start site relevant for the hepatic transcription of this gene. Elements II and III were essential, and I and IV exerted strong modulatory effects. Elements I to III acted as positive regulators, and IV acted as a negative element. Element II contained the sequence TGGCA and is probably a binding site for a nuclear factor related to the known transcription factor NF1. The other three elements did not resemble consensus binding sites for known transcription factors that are involved in the hepatocyte-specific transcription of other well-characterized plasma protein genes, such as the prototype factor HNF-1. Thus, the alpha 1I3 gene achieves its highly hepatocyte-specific transcription through a novel combination of cis-acting control elements and trans-acting factors.

Acute-Phase Proteins↗
PubMed1989

Predictive value of discriminant analysis of monocyte ultrastructure in malignant lymphoma.

Discriminant analysis was applied to morphometric data obtained from ultrastructural studies of blood monocytes from 20 normal subjects, 23 patients with Hodgkin's disease and 12 patients with non-Hodgkin's lymphoma. The aim was to assess the efficiency of predicting subject groups from such data. The analysis, performed on a microcomputer using a standard statistical package, considered nuclear volume, nuclear surface area, nucleolar volume, nucleolar surface area, nucleolar volume fraction, number of nucleoli per section, cell surface area, mitochondrial surface area and subject age. The overall agreement between predicted and actual subject groups was 64%; considering only normality and disease, the agreement was 80%. While the predictive value of such data from circulating monocytes would appear insufficient for diagnostic purposes, discriminant analysis as used here might be of value in indicating the state of host defense in malignancy.

Discriminant Analysis↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

Crystalloid material in cells of the murine mononuclear phagocyte system.

In an attempt to throw further light on the nature and distribution of crystalloid material in macrophages, tissues from a variety of locations in 9 normal adult mice of 36-46 g body weight were studied by light and electron microscopy. Crystalloid inclusions were widely distributed in mononuclear phagocytic cells, being present in macrophages of the bone marrow, spleen, lung and ileum and in the Kupffer cells of the liver. They were not observed in the macrophages of the thymus, parotid lymph node or skin nor were they seen within the lymphatic nodules of Peyer's patches. The observed distribution of crystalloid material seems consistent with its suggested origin from granulocyte breakdown.

Animals↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗