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Observations of Lyell's syndrome in two girls, one 2 and the other 7 years of age, investigated serologically, histologically and by immunofluorescent technique, are reported. In both cases. the disease had been preceded by a prolonged or repeated treatment with acetylsalicylic acid, in the first case in combination with sulphonamides and antibiotics and in the second in combination with mephenytoin. Immunofluorescent staining revealed immunoglobulins in subepidermal blisters and along the dermal vessels. Acetylsalicylic acid has been assumed to have been one of the causative factors of the violent progression of toxic epidermal necrolysis, probably by an antigen-antibody reaction. This has been supported by serologic demonstration of antibodies to acetylsalicylic acid in both cases.

Hyaline cartilage from the knee or rib of newborns was divided in neutral salts into a soluble and insoluble part. The insoluble part was treated with collagenase and was separated into 2 peaks by gel chromatography on Sephadex G-200. The 1st peak revealed a low concentration of proteins, no hydroxyproline, and very high levels or uronates. In the 2nd peak, very high values of hydroxyproline and very low values of uronate were found. Thus the 1st peak contained only proteoglycans and no collagen, while the entire collagen was found in the 2nd peak. The individual fractions were inoculated into rabbits to obtain antibodies. Compared to the fraction containing macromolecular proteoglycans, antisera proved remarkably suitable particularly for analysis of human spleen, yet also of other organs. These anti-cartilage antisera visualized primarily spongy structures of pericapillary sheaths and circumferential reticulum of the periarterial lymphatic sheaths, but to a lesser extent also other extracellular structures of the spleen and of other organs.

The human rib perichondrium is a suitable material for reconstruction interventions on small joints of the hand. Optical and electron microscopy analysis of the human rib perichondrium has shown some features different from the similar perichondrium in rabbits. In its superficial layers there are apart from the vascularity also myelinized nerve fibres, fat-cells and heparinocytes. In the medium layer and in the inner layer of the perichondrium there are cells which by their characteristics correspond to fibrocytes. Among them are collagen fibrillae coated with materials which can be fixed by the ruthenium red. The inner layer cannot be exactly distinguished from the cartilage of the rib.

The simultaneous application of immunofluorescent and enzyme cytochemical methods made it possible to analyze the components of the walls of the arterial branches and arterial capillaries, and particularly the spongy arterial terminals in the red pulp of human spleen. The endothelium was identified by alkaline phosphatase demonstration, the basement membranes (BM) by means of antisera to glomerular BM, the media by using the same antisera, and the adventitia by means by antisera to hyaline cartilage, which are presumed to react particularly with adventitial structures. In the spongy arterial terminals visualized by means of anti-hyaline-cartilage antisera, the endothelium and mostly also BM could be detected, yet the enzyme cytochemical reaction to acid phosphatase and alpha-naphthyl acetate esterase and the immunofluorescent reaction to lysozyme yielded negative reactions. The findings suggest that neither macrophages nor other cells containing the given enzymes in detectable form are accumulated in these structures.

The histology and ultrastructure of the rat gastric mucosa were investigated during 168 hours of starvation. An increased desquamation of individual foveolar cells was found. In the preserved cells of the foveolae, the content of the PAS positive mucosubstances did not change during starvation, and no changes took place in the appearance and in the amount of the mucous granules at the electron microscopic investigation. The number of lipid droplets increased in the mucous foveolar cells within 24 and 48 hours. During starvation the mitochondria (mainly in the parietal cells) were enlarged and contained rare mitochondrial cristae. Some mitochondria were distintegrated and removed by lysosomes. The number of lysosomes (mainly cytosergresomes) was markedly increased n parietal cells. A collapse of the intracellular canaliculi occurred as well as a narrowing in the tubulovesicular profiles. In chief cells the profiles of the granular endoplasmic reticulum and Golgi apparatus were reduced. It was shown that the ultrastructural changes induced by starvation can be interpreted functionally in changed histochemical parameters of the gastric mucosa.

A report is presented on systemic anaphylactic reaction [SAR] of rabbits to bovine serum albumin and ferritin. Active anaphylactic sensibilization with a high yield of sensibilized animals was achieved by administering antigens to rabbits aged a few hours up to 3 months. Tre rabbits showed no presence of precipitins in the circulation, but there were reagins against bovine serum albumin or ferritin. There were various types of SAR activity. Macroscopic findings showed acute emphysema and signs of right heart overload. Apart from acute pulmonary emphysema, histology showed occasional bronchospasm and certain manifestations of RES activation as there was evidence of oedematous infiltration of the peribronchial and perivascular spaces. The above morphological findings cannot as yet be regarded as pathognomonic for SAR.

Endothelial histogenesis of sarcoma Kaposi was referred to in a case of 36-year old man studied by electron microscopy. Characteristic features corresponding to the literature were found: Weibel-Palade bodies, a ferritin-like material, phagocytosed erythrocytes, nuclear bodies, microfilaments and microtubules. Myelinated and unmyelinated axons were considered as remnants of original nervous tissue destroyed by the tumour or as nerve fibres accompanying proliferated vascular structures.

Periapical granulomas have been investigated histologically, immunohistologically using polyclonal and monoclonal antibodies, as well as electronmicroscopically. Lesions were formed by inflammatory granulation tissue frequently with foci of purulent exudation and fibrosis. Most numerous were plasma cells usually in cellular regions of the granulation tissue where they were tightly pressed. Of other cellular types were numerous lymphocytes, fibroblasts, less frequent were macrophages, scattered granulocytes and mast cells. More than a half of the plasma cells were IgG positive, about 20% IgA positive, up to 10% IgM, rarely IgE and sporadically IgD positive cells. In the vascular walls and their surrounding as well as in the phagocytes fine granular to granular positivities of C3 and C4 components of the complement were present. The majority of lymphocytes beared markers of T lymphocytes of which the T-suppressor markedly prevailed over the T-helper lymphocytes. In electron microscopy the plasma cells were most frequent. They were usually close to each other, sometimes with a disintegrated cytoplasmic membrane and non-damaged organelles being free around the nucleus. Mast cells were numerous and did not show any signs of marked degranulation. Rich production of immunoglobulins as well as the presence of IgG and IgM positive material in phagocytes, and the presence of positivities of the C3 and C4 components of the complement in the surrounding of the vessels and in phagocytes on the other hand supported the presumption that immune complexes participate in the pathogenesis of periapical granulomas. In spite of the presence of the IgE producing cells the morphological picture of mast cells did not suggest the presence of anaphylactic reaction in periapical lesions. Diffuse distribution of T lymphocytes, moreover with the prevalence of T-suppressor/cytotoxic over T-helper lymphocytes and not numerous macrophages in the inflammatory infiltrates did not suggest the participation of a typical cell-mediated immunity reaction in the development of periapical granulomas. Numerous T-suppressor/cytotoxic lymphocytes and low numbers of macrophages can be important factors of the chronicity of periapical inflammatory diseases.

In the human spleen we failed to find marginal zone bridging channels which in rats and mice are said to serve as return routes for lymphocytes from the white into the red pulp. In human spleens, using anticartilaginous antisera which distinctly visualized extracellular structures, in some parts we found the periarterial lymphocyte sheath to be closely attached to the red pulp, so that lymphocytes and other material could pass from the white pulp directly into the red pulp and vice versa. The strips of reticular fibres that seemed to bridge the marginal zone between the follicles and the red pulp proved to be components of reticular structures around the arteries, passing from the periarterial lymphocyte sheath into the follicles or from the follicles through the marginal zone into the red pulp.

Diagnosis and pharmacological control of shock represent the problems of everyday public health practice. Our experimental approach using three different shock models contributes to further elucidation of the pathogenesis of haemorrhagic shock as well as shock developing during systemic anaphylactic reaction (SAR) and systemic immunocomplex reaction (SIR). It could help to explain why adequate diagnosis and application of mostly proved and commonly used therapeutic procedures may fail under some conditions. For the future, based on our and other experimental data obtained in particular by techniques of electron microscopy, it will be perhaps possible to consider some new interpretations of findings occurring in humans who died in shock reactions and in those with a suspicion of clinically diagnosed shock respectively.

The administration of a sufficient dose of heterologous antibodies against renal glomeruli in rats produces symptoms of respiratory insufficiency and pulmonary oedema causing death of the animals. Under these experimental conditions the basic pathogenic mechanism appears to be binding of the injected antibodies on the basement membrane structures of pulmonary capillaries resulting in their damage. Such changes are followed by widespread haemorrhagic exsudative changes in the lungs. Localization of the injected antiglomerular antibodies has been studied with the aid of immunohistochemical methods and in addition, by a method using antibodies labelled with radioactive isotopes of iodine, the so-called "paired administration technique". After the administration of a lethal dose of antiglomerular antibodies, they later appeared to be predominantly localized in the lungs. This fact correlates well with the idea of the effect of the antibodies upon pulmonary parenchyma in the present experiment. A remarkable finding was a rather high localization of the injected antibodies in the liver parenchyma which could be explained either by a cross reaction between the antibodies and the antigens of hepatic vascular spaces, or by a shock reaction associated with heart failure and circulatory disturbances.

Immunohistochemical methods were employed for the investigation of bioptic and necroptic material fixed in formol and embedded in paraffin after it had produced very little or no fluorescence at all in the use of routine immunofluorescence techniques. Partial digestion with pepsin or trypsin or both enzymes in succession mostly facilitated positive immunohistological reaction. This particular procedure gives more scope to the methodological possibilities of histological material examination in that it offers an opportunity for the immunohistological investigation of even old material not specially preserved for immunohistological purposes but routinely fixed in ordinary formol. The simplification adds general availability to the method.

The present paper investigated the effect of restricted feeding (11.00 to 13.00 h) by a single daily meal upon the activity of various oxidoreductases of the rat gastric mucosa (SDH, alpha-GPDH, LDH, NADHTR), which at ad libitum feeding under normal lighting conditions with a dark night were shown to have distinct circadian activity variations related to the rat's nocturnal food intake preference (Zaviacic and Brozman 1978a). 1st part of the animals received food in 2-h-period by natural daylight (natural lighting conditions), the 2nd part at the same period of time but in the dark (lighting conditions reversed to natural). Checking the consumption of food, we found the animals to become adapted to the new time of food intake beginning with the 6th experimental day. The circadian rhythm of enzymes was examined on days 69, 83, 97, and 104 of limited feeding under the defined lighting schedule, at 06.00 h, 12.00 h, 18.00 h, and 24.00 h in groups of 5 animals. Synchronization of the highest dehydrogenases activities (particularly of SDH) with the time of restricted feeding was seen to develop in the gastric mucosa of the rat. The synchronization effect was more pronounced in the animals which received their food in the dark (and here even more in male than in female). The effect of light during food intake was found to be rather interfering with the development of synchronization of dehydrogenase activities with the time of food intake, and the influence was again more marked in male than in female. The time of food intake was at the feeding schedule restricted to daytime intake the main synchronizer for the circadian rhythm of oxidoreductases of the gastric mucosa of the rat, with the highest daily activities recorded around the feeding time and the lowest activities at night, which is the direct opposite of the circadian rhythm of the same enzymes determined in rats fed ad libitum under normal lighting conditions with a dark night.

Electron microscopic findings of the effects of exposure to the cancerogenic substance N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) upon the gastric mucosa of rats are presented. MNNG was administered in drinking water at a concentration of 83 mg/l over a period of eight weeks. The resulting findings included occurrence of myelin figures in membrane structures of epithelial cells, occasional disappearance of nuclear membrane, numerous intranuclear cytoplasmic pseudoinclusions, and increased number of perichromatin and interchromatin granules and of nuclear corpuscles. Narrowing of the layer of peripheral condensed chromatin and broadening of the layer of dispersed chromatin were frequently observed. In the cytoplasm of epithelial cells, production of autophagous vacuoles was detected in differentiated types of cells, the presence of great amount of polysomes and profiles of rough endoplasmic reticulum diversely deformed was seen in the undifferentiated neck cells. These cells presented a marked proliferative activity. Some of the changes described in the nuclei of epithelial cells were also observed in different mesenchymal elements in the lamina propria mucosae. The demonstrated changes are indicative of both regressive and progressive effects of the cancerogen used in our experiment.