alpha1-macroglobulin (alpha1-M) was demonstrated by indirect immunofluorescence staining on the surface membrane of leucocytes obtained from rat blood and lymphoid tissue. The incidence of alpha1-M positive cells correlated with serum levels of the protein. Compared with blood, a significantly higher percentage of staining cells was demonstrated in spleen and lumbar lymph nodes. During pregnancy, when serum levels of alpha1-M were significantly elevated, the proportion of alpha1-M staining leucocytes increased in blood, Thymus and lymph nodes but the incidence of alpha1-M positive spleen cells was unaffected. The comparatively low incidence of alpha1-M staining thymocytes, together with the presence of alpha1-M on glass-adherent cells and on leucocytes from congenitally athymic rats, suggest that this protein is associated predominantly with B cells and monocytes.
The structure of bronchial carcinoids, oat cell carcinomas and pulmonary 'tumourlets' is described and evidence presented that they are related histogenetically, all being derived from certain specialized cells of endocrine or chemoreceptor nature found within the lining epithelium of the airways. Chemoreceptors related to pulmonary blood vessels have also been identified and two different types of pulmonary tumour have both been termed chemodectoma in the belief that they arise from such structures: these are the so-called multiple minute chemodectoma and the larger solitary variety but the exact histogenesis of both these tumours must remain conjectural at present.
A description of the gastroenteropancreatic cells as identified by immunocytochemical techniques is presented. A functional classification of these cells is proposed where function is defined as the production of a chemical messenger be it a polypeptide or a biogenic amine. The discovery of the polypeptide-containing neurons has created a new area for investigation. This will be outlined briefly although the majority of the peptidergic-type synaptic profiles have as yet to be linked with the production of a particular polypeptide.
The structure of calcitonin in several species has been determined and its mode of action is now well established. The function of this hormone in man is still not completely understood but one role appears to be maintenance of the skeleton. It seems likely that future research in this field will be of great significance in understanding the mechanisms of disorders of skeletal metabolism.
Patterns of mucus secretion were investigated, by histochemical methods, in 24 colectomy specimens resected for familial polyposis coli. In this pre-malignant condition, mucus secretion contained an increased proportion of sialomucins as compared with normal colonic mucosa where sulphomucins predominate. These mucin changes (a) were more extensive in the left colon than in the right; (b) although consistently present in the mucosa adjacent to carcinomas, independent of their site, and around large polyps, they were also seen in patches of mucosa distant from the neoplastic growth; (c) they were more marked in the non-involved mucosa from patients who had developed carcinoma than in the non-cancer group. It was not possible to relate the type of mucin secreted and the degree of dysplasia. Similar alterations in mucus secretion have been previously described in colonic mucosa harbouring carcinoma both in humans and experimentally in rats, suggesting a relationship between altered glycoprotein synthesis and malignancy. The present results add further evidence to this hypothesis.
Development of the secondary palate was studied in the chick embryo using light and electron microscopic and histochemical techniques. The palatal shelves develop as horizontal outgrowths of the maxilla on day 6 of incubation (HH stage 29). During the next 2 days (HH stages 30-33) the shelves continue their growth toward the midline, and on day 9 (HH stage 34) they approximate. At no time do the approximating shelves form direct contacts. Ultrastructural and histochemical observations indicate that the midline epithelia of the opposite shelves differentiate into a stratified squamous pattern. Unlike rodents and humans, the midline epithelial cells of the chick embryonic palate are not programmed to die. Other features of cellular differentiation such as the appearance of intracytoplasmic tonofilaments and glycogen, seen in species where palatal fusion occurs, were absent during palatogenesis in the chick. It is suggested that morphogenesis of the palate in chick embryos is different from that in the rodents, primates and humans. These differences are attributed to the pattern of subcellular differentiation in the palatal tissues.
Carcinoembryonic antigen (CEA) was measured in the plasma by radioimmunoassay in 80 patients who were referred because of an apparently resectable lung cancer. There was no correlation between the initial CEA level and survival in patient whose tumours were found to be inoperable or had metastasized, with only 2 of 37 patients surviving longer than 2 years. Following a curative resection, the median survival for patients with initial CEA greater than 40 micrograms l-1 was 6 months compared to 14 months for those with CEA in the range 20-40 micrograms l-1, while 56 per cent of those with CEA less than 20 micrograms l-1 are still alive at 2 years. This trend was found to be highly significant (P < 0.005). Twenty-five per cent of all patients had an initial CEA greater than 40 micrograms l-1 and this was associated with a poor prognosis, despite complete surgical removal of the primary tumour. Such elevations, if discovered in the preoperative assessment, indicate a need for a thorough search for metastases.
The epithelium bordering gastric carcinoma may show altered patterns of mucin secretion. The development of adenocarcinoma in the rat stomach was studied histochemically to determine whether similar mucin changes might precede malignant transformation. Male Wistar rats were fed N-methyl-N'-nitro-N-nitrosoguanidine (83 mg/l) ad libitum for 7 months. The stomachs were examined histologically and by special methods to distinguish neutral and acid mucins. Hyperplasia was observed as an early change in both antrum and body and was characterized by lengthening of foveolae and neck zones. This was accompanied by increased acid mucin secretion. Dysplastic change began in the proliferating neck zone of hyperplastic foci. These findings suggest that altered mucus secretion may be a feature of early malignant change.
The population density of alveolar macrophages was measured in the lungs of hypoxic rats, in rats which had recovered from a period of hypoxia, and in untreated controls. Alveolar macrophages were most numerous in hypoxic animals. The recovery group contained fewer macrophages than the hypoxic group but more than the controls. In the hypoxic animals the distribution of alveolar macrophages was not homogeneous either within an individual rat or amongst the group as a whole. This suggests that the increase in their number may be stimulated by the secondary effects of hypoxia rather than by its direct interference with their metabolism.
Thirty adrenal glands from patients with adreno-leukodystrophy (ALD) have been studied by light microscopy, three by enzyme histochemistry, three by electron microscopy and two by tissue culture. Cytoplasmic ballooning and striations result from proliferation of smooth endoplasmic reticulum and accumulations of lamellar-lipid profiles and clear clefts (crystalloids). Striated adrenocortical cells, the only pathognomonic adrenal lesion in ALD, display cytoplasmic lamellae, decreased amounts of rough endoplasmic reticulum and depression of several enzymes (alpha-glycerophosphate dehydrogenase, 3 beta-hydroxysteroid dehydrogenase and TPNH diaphorase). The striated cells also demonstrate decreased ability to adapt to changes in microenvironment, both in vivo and in vitro. A blunted response by striated cells to focal peripheral cytolysis leads to cytoplasmic erosion, atrophy and macrovacuoles. ACTH has a pivotal role in the evolution of these lesions. We propose that the pathognomonic lamellae of ALD basically represent bilayers or bimolecular leaflets of very long chain saturated fatty acids, while lamellar-lipid profiles and clefts contain cholesterol esterified to these abnormal fatty acids. The similarity of lamellar-lipid profiles of ALD to cytoplasmic lesions induced by long chain saturated fatty acids suggests that the very long chain saturated fatty acids isolated in ALD are cytotoxic and are responsible for adrenocortical cell dysfunction in this disease.
Cleft palate was induced in fetuses by administration of triamcinolone to pregnant hamsters. Twenty hours after treatment, alterations were seen at the epithelial-mesenchymal interface in the prospective fusion epithelium of the vertical shelf. The alterations included contacts between the epithelial and mesenchymal cells, and disruptions in the continuity of the basal lamina. Thirty-two hours after triamcinolone treatment, the basal epithelial cells in some of the reorienting palatal shelves were necrotic. When compared with normal cells, the drug treated necrotic cells were lighter in appearance due to reduced polyribosomes; they also lacked lysosomes. In other reorienting shelves, the basal cells were lost and the epithelial continutity was maintained by the superficial cells. The alterations at the epithelial-mesenchymal interface, and the necrotic changes in the basal cells, became more severe with delayed horizontal reorientation of the palatal shelves. The necrotic debris was cleared by macrophages. At a later stage, the opposing epithelia of the horizontal shelves did not fuse but underwent stratification. It appears that triamcinolone induces alterations at the epithelial-mesenchymal interface, and inhibits the normal process of protein synthesis in the epithelial cells during palatogenesis. This, along with delayed differentiation of mesenchymal cells, distrupts the timing of coordinated development of the palatal tissues. These changes are associated with a delay in the reorientation of the palatine shelves, and cleft palate results.
The association is reported between the presence of plasma cells and sinus catarrh in the axilary lymph nodes from patients with breast carcinoma without nodal metastases, and their later death from disseminated disease. Patients surviving at 5 years showed predominantly parcortical reaction with sinus histiocytosis.
The pathology of post-parturient fatty liver has been studied in a group of 20 high-yielding dairy cows; 10 had less than 20 per cent fat in the liver cell and were classified as having a mild fatty liver and 10 had more than 30 per cent fat in the liver cell and were classified as having severe fatty liver. Severe fatty liver was accompanied by a number of morphological changes including the occurrence of lipogranulomas, increased liver cell volume, decreased volume of rough endoplasmic reticulum per liver cell and evidence of mitochondrial damage. The latter two changes were reflected in reduced albumin levels and increased activities of mitochondrial enzymes observed in the blood of cows with severe fatty liver. Reduced fertility may be one of the consequences of severe fatty liver in the dairy cow.
Pregnancy-associated alpha2-glycoprotein (alpha2-PAG) is well-characterized high molecular weight human plasma protein detectable in normal individuals of both sexes. Circulating levels are related to sex and age and are increased following administration of oestrogens and in pregnancy. While alpha2-PAG production during gestation is dependent on a functional foeta-placental unit it is leucocyte-derived, although perhaps not exclusively so. There have been several reports of raised alpha2-PAG levels in a variety of malignant conditions, although this finding has been disputed. Further controversy exists over the true value of alpha2-PAG measurements in monitoring the course of malignant disease. The exact function(s) of alpha2-PAG is uncertain but there is considerable evidence that it is a non-specific immune suppressant.
When the axillary nodes contain tumour, the prognosis in breast carcinoma is poor. Preliminary results suggest that a combination of efferent vascular invasion of the axillary nodes and oestrogen receptor analysis on the primary tumour may enable a more individual prognosis to be given at the time of operation. The risk of early recurrence is greatest in patients with efferent vascular invasion and an oestrogen receptor negative primary tumour.
Rat glomerular epithelial and mesangial cells, and rat skin fibroblasts, were cultured in RPMI medium containing 15% decomplemented fetal bovine serum. They were incubated for 1 h at 37 degrees C with 2 mM [Ca2+]. At that time, their response to various concentrations of angiotensin II, norepinephrine and carbamylcholine was studied by phase contrast microscopy. Only the mesangial cells exhibited contractile activity in the presence of 10(-10) M angiotensin II and 10(-6) M norepinephrine, as demonstrated by the reduction of their length or, more frequently, by modification of their shape. No contractile activity was observed in the presence of 10(-5) M carbamylcholine. The percentage of contractile cells increased proportionally to the concentration of angiotensin II, reaching about 35% with 10(-6) M angiotensin II. The contractile activity was reversible. Specific inhibitors, i.e. Sar1-ala8-angiotensin II and phenoxybenzamine, when administered in concentrations 10 to 100-fold higher than that of the corresponding agonists, completely blocked the contractile response. This competitive effect was also reversible. The data, therefore, suggest that mesangial cells in culture display some functional properties of smooth muscle cells.
