Quantitative histological studies on the lung are time consuming and for the pathologist may not reveal much additional imformation in relation to the time spent. Sixty-eight cases of emphysema were studied. The percentages of the lung tissue destroyed by alveolar, bronchiolar and bullous emphysema were determined by macroscopic point counting. The internal surface area (I.S.A.) and internal surface area at a standard lung volume of 3,000 ml(I.S.A.3,000) were determined by the mean linear intercept (M.L.I.) method. There was a significant correlation between both the M.L.I. and I.S.A.3,000 and the percentage of lung tissue destroyed. The M.L.I. was the most accurate guide to the presence of emphysema. The I.S.A. was the least reliable indication of emphysema. Cases of alveolar duct emphysema were both over and underdiagnosed on macroscopic point counting. It is therefore suggested that in cases with alveolar duct emphysema, apparently normal lungs or where full pulmonary function tests are available, quantitative histological studies should be carried out. In other cases it is possible to derive the I.S.A. and I.S.A.3,000 from the percentage of emphysema as determined macroscopically, without recourse to histological methods.
The ultrastructure of the Guérin tumour T-8 is described. Although this transplantable tumour has its ancestry in an uterine adenocarcinoma, there is no more evidence of gland formation. Desmosomes, or any other form of cell attachment organelle, were totally absent. The tumour has now a very anaplastic sarcomatous appearance.
The ultrastructure of megakaryocytes was examined in eight patients with idiopathic thrombocytopenic purpura (ITP) and the results were compared with those obtained from controls and with data obtained from platelet kinetic studies. Platelet production was significantly increased in (ITP) and related to the megakaryocyte number and volume. In all cases of ITP megakaryocytes containing tubular demarcation membranes were found. The granular content and the distribution of the demarcation membrane system in these megakaryocytes from cases of ITP were similar to those features seen in normal cells of the same degree of maturity. In three cases of ITP an increased content of a dilated demarcation membrane system was found in promegakaryocytes and granular megakaryocytes, in one of these cases with the additional formation of large membrane complexes. The ultrastructural findings lend support to the results obtained from the thrombokinetic studies namely that the megakaryocytes in the bone marrow react to thrombocytopenia with an increased production of platelets.
In the course of two chronic experiments including the administration of N-2-acetylaminofluorene (N-A-AF) to male Wistar rats, alterations were observed in the fine structure of the nuclei isolated from the liver. After the first 3 to 4 months of ingestion of the carcinogen, the heterochromatin became uniformly distributed throughout the nucleus, with dissociation of the nucleolus-associated heterochromatin. At longer intervals (7 months) evidence was found in the nucleus of various types of inclusions, chiefly granular virus-like bodies. Subsequently, the frequency of inclusions diminished but the liver cell nucleus remained large, with numerous large nucleoli. This suggested the existence of a stage of metabolic activation of the liver cell nucleus in the course of experimental induction of hepatocarcinoma with N-A-AF, giving rise to an increase in the nuclear and nucleolar volume by accumulation of synthesis products and disorders in nucleo-cytoplasmic exchanges.
Parallel morphometric, karyometric and ultrastructural studies of the aortic wall in Okamoto-Aoki rats with short term (3-6 months) and long-term (12-16 months) spontaneous hypertension have revealed a progressive thickening of the medial layer, which is associated with an increaase in the mean nuclear area of the arterial medial smooth muscles and reduction in their mean number per unit area. Electron microscopic studies have shown a multiplication of the intracellular components of aortic smooth muscle cells as a base for their enlargement, as well as small single foci of smooth muscle hyperplasia in the area of the innermost interlamellar space in parts of the aortic wall with intimal thickening. Results of these studies allow the conclusion, that hypertrophy is a reaction of arterial smooth muscle cells to an increased mechanical load in hypertension which, in turn, is responsible for the thickening of arterial with Hyperplasia - increase in smooth muscle cells' number in the media - played a subordinate role. The reaction of the aortic wall to elevate blood pressure is interpreted as a manifestation of the normally limited division capacity of smooth muscle cells in mammals, which does not allow an increase in its cellular components. The function of existing arterial smooth muscle smooth cells is enhanced, instead, by hyperplasia of their specific organelles and augmentation of their volume.
Six patients, two with acute lymphoblastic leukaemia (A.L.L.) and four with lymphosarcoma with early transformation into A.L.L., have been studied. All blast-cells demonstrated with cytological, cytochemical and ultrastructural features of Burkitt's tumour. The clinical evolution was fulminant and there was no remission of long duration despite intensive chemotherapy. The cytoplasm of the blast-cells displayed a great number of lipid droplets. The level of the anticapsid Epstein-Barr virus antibodies was high in the case investigated.
The normal squamous epithelium of the uterine cervix was investigated in 50 foetuses and newborns, as well as in 207 adult women operated upon because of various benign conditions of the uterus. The epithelium was divided according to the presence or the absence of prominent epithelial papillae. Epithelial papillae occurred in 32% of the cervices in the paediatric age and in 17% in adult women. They were present in the whole squamous epithelium covering the portio vaginalis in all pediatric patients. In 49% of the adult patients epithelial papillae covered the whole portio and/or the transitional zone; in the remaining 51% only a reduced area presented epithelial papillae. Micrometric determinations demonstrated that normal epithelium with papillar formation was thicker than epithelium with smooth epithelial border. This was most prominent in the paediatric patients. The possibility that oestrogenic stimulation (in paediatric patients) and oestrogenic stimulation as well as chronic stromal inflammation (in adult patients) could account for the formation of prominent epithelial papillae was discussed.
The present study applied methods of stereologic cytology to clinically specified lesions of leukoplakia simplex which originated from the oral mucous membrane at the cheek and the floor of the mouth. The data provided the following evidence: (1) The structure of and the differentiation gradients for various cytoplasmic constituents in leukoplakia simplex epithelium were identical at both sites. (2) The differentiation pattern of leukoplakic epithelia was adversely different from that of the respective normal epithelium. (3) This alteration which resulted in a striking resemblance between the leukoplakic epithelia and those of normal skin or hard palatum conceivably can be regarded as a squamous metaplasia characterized by the conversion of one differentiation pattern into another. (4) This shift in the differentiation pattern hardly could have been disclosed by means other than stereologic morphometry.
Tumour formation from single or repeated small i.v. tumour cell doses was studied in a syngeneic tumour-host system. Only marginal differences were observed between different dose schedules, once the critical cell dose level was surpassed.
The endothelial and sub-endothelial lesions during early stages of experimental atherogenesis and scurvy have been studied by means of scanning EM and transmission EM, making use also of the Con-A reaction. The surface coat modifications were accompanied by formation of vacuoles in the endothelial cells and by sub-endothelial 'oedema', not only in rabbits fed a hypercholesterolic diet but also in scorbutic guinea pigs. The endothelial lesions were sometimes found even before clear modifications of the Con-A surface reactive layer were apparent.
Colon biopsies from 37 young patients with active ulcerative colitis (UC) were investigated by electron microscopy with special regard to the inflammatory infiltrate of the lamina propria mucosae, which is characterized by lymphocytes, macrophages and plasma cells. There are close topographical relations between plasma cells and other inflammatory cells. In particular, different forms of plasma cells occur, which mainly differ in shape and contents of their rough endoplasmic reticulum (RER). The different degrees of development and dilatation of the RER express different functional states. The frequent occurrence of Russell bodies, Mott cells and necrobiotic plasma cells is explained as a--at least partial--pathologic alteration of plasma cells in UC. In context with recently published immunohistochemical findings these observations permit the assumption of an imbalance of the local Ig-system in UC.
The regional lymph nodes of the parotid gland of rats were examined histologically. The nodes were removed from untreated animals or rats given instillations of BSA or saline into the parotid duct. Anti-BSA antibodies were assessed in the saliva and serum. Patterns of reactivity of the lymph nodes did not correlate with the presence or absence of salivary and serum antibodies. The occurrence of antibodies in the saliva appears to reflect the activity of immunocytes residing in the parotid gland. The morphological features of the lymph nodes correspond to the overall immunological experience.
The value of a number of in vitro systems which have been used in the investigation of carcinomas of colon and rectum is considered. Tissue culture cell ines which have been established from human and mouse rectal and colon tumours are described. Both mouse and human cells retain ultrastructural features of the tumours of origin; acinus formations, junctional complexes, microvilli with surface glycoprotein strands. Normal colo-rectal epithelium has not been established in cell culture but organ cultures of mouse colon, which retain normal ultrastructural features can be maintained for at least 28 days. The possible origin of non-epithelial cells which appear in cultures from normal colon is discussed. The areas in which the various in vitro systems may be of used are reviewed.
Quantitative histological studies on the lung are time consuming and for the pathologist may not reveal much additional imformation in relation to the time spent. Sixty-eight cases of emphysema were studied. The percentages of the lung tissue destroyed by alveolar, bronchiolar and bullous emphysema were determined by macroscopic point counting. The internal surface area (I.S.A.) and internal surface area at a standard lung volume of 3,000 ml(I.S.A.3,000) were determined by the mean linear intercept (M.L.I.) method. There was a significant correlation between both the M.L.I. and I.S.A.3,000 and the percentage of lung tissue destroyed. The M.L.I. was the most accurate guide to the presence of emphysema. The I.S.A. was the least reliable indication of emphysema. Cases of alveolar duct emphysema were both over and underdiagnosed on macroscopic point counting. It is therefore suggested that in cases with alveolar duct emphysema, apparently normal lungs or where full pulmonary function tests are available, quantitative histological studies should be carried out. In other cases it is possible to derive the I.S.A. and I.S.A.3,000 from the percentage of emphysema as determined macroscopically, without recourse to histological methods.
Antenatal diagnosis of hereditary disease is highly dependent on sufficient theoretical knowledge and on a number of practical methods of studying the foetus such as obtaining, cultivating and assaying amniotic fluid cells. Knowledge of the primary defect in any monogenic disorder cannon be used in prenatal diagnosis unless the metabolic error is expressed in vitro. Modern cytogenetics can diagnose in utero a large majority of karyotyping abnormalities although the karyotype-phenotype correlation is not an absolute one. This task must be assigned to special laboratories where technical pitfalls are reliably avoided. In both metabolic and chromosomal hereditary disease, the pathologist can confirm and extend the phenotypic findings and improve knowledge on foetal features and physiopathology. Pathology is the more important, the less means of in utero diagnosis are available as in the non-chromosomal syndromes of localized or multiple malformations. Here it helps eliminating a present major drawback of prenatal diagnosis: the lack of a strict diagnosis in the previous patient in a family at risk.
Lymphoid cells of C57BL mice bearing a syngeneic sarcoma are cytotoxic against the same tumour cells in vitro at two different periods of the growth of the tumour separated by a "mute period". Without additional antigenic stimulation the lymphoid cells from the "mute period" can be made cytotoxic by preincubation in vitro and elimination of adherent cells by a passage through a glass bead column. Either of these treatments alone is inefficient. The cytotoxicity revealed in this way is due to cells with different properties than those that are directly cytotoxic during the 4th week of the tumour growth. The significance of these results is discussed. It is suggested that some other cells have to be eliminated because they compete with or inhibit the activity of the "mute period" lymphoid cells made cytotoxic by preincubation.
Nine days after receiving a single injection of ethidium bromide - an inhibitor of mitochondrial DNA and its synthesis - mice were found to have enlarged mitochondria which were also reduced in number. The morphometric study revealed an increase of the mean mitochondrial volume, as well as an enlargement of the surface area of the mitochondrial inner membrane. However, the surface of the inner and outer membrane per unit volume of mitochondrion remained unchanged. These morphometric findings suggest mitochondrial growth, since mitochondrial inner membranes can be synthesized even in the presence of DNA-inhibiting ethidium bromide. In addition, morphometric analysis enables us to estimate the mean life span of hepatic mitochondria. In conclusion we may assume that since ethidium bromide induces not only a reduction of mitochondrial division but also an increase in the hepatic mitochondrial volume and inner membrane, the mitochondrial genome possibly fulfills a regulatory role in the mitochondrial and cytoplasmic systems for protein synthesis.
A small but significant number of tritiated thymidine labelled cells were found, by autoradiography, in the glomeruli of rats with Masugi nephritis or chronic serum sickness nephritis. There were no labelled glomerular cells in sections of untreated animals. The findings favour the contention that in proliferative glomerulonephritis, glomerular hypercellularity is due to infiltration of monocytic cells into the tufts where they divide.
Three patients with a giant-cell tumour of bone were studied clinically, roentgenologically and morphologically, using cytological, histopathological and electron microscopic methods. The tumours were composed of giant cells possessing a great number of mitochondria and stromal cells exhibiting prominent endoplasmic reticulum and Golgi complex. Mitotic activity was only found among the stromal cells. Autophagic vacuoles, lysosomal bodies and degenerative changes of varying severity were found mainly or exclusively among the giant cells, which may indicate that these cells represent an involutionary form of tumour cell. The giant-cell tumours of bone are believed to arise from undifferentiated cells of the bone marrow. Fine-needle aspiration biopsy represents a valuable complement to histopathological examination in the identification of giant cell lesions and diagnosis of genuine cell tumours of bone.
