Biomedical subjects
Publications and source records attributed to I Carr.
Macrophages in granulomas in four rodent species contain cytoplasmic granules with an ordered substructure similar to those previously described in human granuloma macrophages. These appearances, as well as other ultrastructural features of the cells, are compatible with the view that those macrophages have a secretory function.
The giant cells (multinucleate macrophages) of human sarcoidosis have been shown by the unlabelled antibody immunoperoxidase technique at electron microscope level to contain lysozyme within cytoplasmic granules.
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Spleen-cell sensitivity to encephalitogenic factor (EF) was measured with the macrophage migration inhibition (MMI) test over a period of time in hamsters inoculated with SV40-transformed tumour cells and in rats treated with 4-dimethylamino-3'-methylazobenzene.Spleen cells from hamsters receiving 10 or 10(3) SV40 tumour cells gave inhibition of macrophage migration with EF at a significance level of P<0·05 21 days after implantation. Spleen cells from animals receiving 10(5) tumour cells gave inhibition at a significance level of P<0·001 after the same interval.Spleen-cell sensitivity to EF, and the abrogation of this sensitivity by serum, was investigated over a period of time in rats undergoing hepatocarcinogenesis. Sensitivity to EF was seen in 2/10 animals (20%) with minimal lesions of the liver, in 2/16 animals (12%) with proliferative changes and/or cholangiofibrosis, in 7/15 animals (46%) with dysplastic lesions of portal-tract epithelial cells and in all 5 animals with cholangiocarcinoma. None of a control group of 10 animals showed any response to EF. Autologous serum abrogated the spleen-cell response to EF in one sensitized animal with proliferative changes and cholangiofibrosis, in all 7 sensitized animals with dysplastic hepatic lesions and in 4/5 sensitized animals with cholangiocarcinoma. Autologous serum had no effect on macrophage migration in the 10 control animals.These findings indicate that a progressive increase in sensitization to EF occurs during carcinogenesis and is evident at the point of preneoplastic dysplasia. This has an obviously important bearing on the clinical use of such tests.
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Human macrophages in the lesion of sarcoidosis contain cytoplasmic granules with an ordered paracrystalline substructure. Similar though less ordered granules are seen in human macrophages elsewhere. These appearances as well as the general ultrastructure of the cell are compatible with the view that these macrophages have a secretory function.
The case is argued for wider use of electron microscopy as an aid to histological diagnosis in problem cases such as tumours of uncertain histogenesis. In practical terms, electron microscopy can produce results as "immediate" as many special stains in regular use. The cost of providing an effective service can be favourably compared with that of various other diagnostic aids commonly called upon in normal clinical practice. It is suggested that exploitation of this growth area of morphological pathology will enhance the attractions of the discipline of histopathology to talented potential recruits.
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Neoplastic invasion as seen in the rat Rd/3 neoplasm has been studied electron microscopically in three sites: abdominal wall, footpad and liver. This neoplasm invades by peripheral cell division and active cell migration. Neoplastic cells protrude many fine processes and compress host cells. Neoplastic cells invade lymphatic vessels in a way similar to that in which white blood cells penetrate them - by the protrusion of fine cytoplasmic processes and passage, sometimes in clumps through open cell junctions. There is no ultrastructural evidence of secretory phenomena.
The growth and structure of a virus-induced tumour has been studied in normal and immunised animals. Retardation of tumour growth in immunised animals is accompanied by a lymphoreticular infiltrate; macrophages ingest apparently intact tumour cells.
The projected areas of nuclei of tumour cells in experimental and human tumours have been measured with a Quantimet. In nearly all the specimens examined the nuclei in the lymph node metastasis, and the nuclei in the site from which metastasis had occurred, were similar in size. In one case of human breast cancer, nuclei in the axillary nodal metastasis were twice as large as those in the mammary primary. In another case of human breast cancer a few very large nuclei were seen only in the mammary primary.
Injection of a soluble tumour extract induces mitosis in sinus macrophages of the draining lymph-node. This is not abolished by irradiation; the stimulus also induces monocytosis somewhat later. These findings make it likely that the stimulus induces mitosis in the resident lymph-node macrophage population.
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