Three cases of congenital alcoholic cardiomyopathy and cardiac defects in children are described. The mothers were heavy spirits drinkers. One child had a ventricular septal defect, two had Fallot's tetralogy, all requiring operation. At open-heart surgery left-ventricular myocardial biopsies were obtained in all three children. Histological and electronmicroscopic examination revealed primary toxic and hypotrophic changes, which differed from those seen in alcoholic cardiomyopathy of the adult. The cells, their nuclei and the myofibrils had reduced diameters. The mitochondria were damaged to differing extent. The myofibrils were arranged in parallel and some had contraction bands and ruptures. The sarcoplasmic reticulum was dilated and had vacuoles. The cell surface penetrated into the interstitial tissue. All these changes could have resulted from inhibited embryofetal cell growth and cytotoxic damage by alcohol during pregnancy. It would seem that alcoholic cardiomyopathy occurs only in extreme forms of alcohol abuse during pregnancy. The prognosis is as yet unknown.

Zunächst wird die unterschiedliche Enzymaktivität in der Leber junger und gealterter Ratten beschrieben. Dann wird mitgeteilt, wie sich die Aktivität der Glutamat-Oxalacetat-Transaminase (GOT) alter Tiere bei verschiedenen Diätformen verhält: Hierfür wurden Ratten 2 Jahre lang überwiegend mit Kohlenhydraten, Protein bzw. Fett ernährt. Es zeigte sich, daß die GOT-Aktivität im Alter bei normaler sowie bei kohlenhydrat- und fettreicher Kost gegenüber jungen Tieren absinkt. Dagegen hatte die proteinreich ernährte Tiergruppe die gleiche, hohe Enzymaktivität wie die Gruppe der jungen Tiere.

Generalized gangliosidosis GM1 is characterized by the almost complete deficiency of the enzyme β-galactosidase, therefore the cleavage of the terminal galactose from the gangliosid GM1 is impaired.

Cryostat sections of endomyocardial biopsies from 53 patients (mean age 41 +/- 5 years, 38 male and 15 female) clinically indicated to suffer from myocarditis were stained using monoclonal antibodies against subpopulations of T-lymphocytes and macrophages and with polyclonal rabbit-anti-human sera marking two calcium-binding proteins expressed by monocytes and macrophages appearing in inflammatory sites only. No inflammatory infiltrate cells were found in 13 cases (25%). Mononuclear cell infiltrates were present in 40 cases (75%). Ten biopsies showed a predominance of macrophages bearing the marker 27E10, characteristic for an early acute inflammation and 18 biopsies contained 25F9 positive macrophages, characteristic for a late stage of inflammation. An intermediate type of inflammation with both macrophage types present was found in 12 patients. Patients with immunohistologically confirmed myocarditis had atrial, ventricular or combined forms of arrhythmias (78%), scars in the vectorcardiogram (100%) and radiological evidence of cardiomegaly (36%). In conclusion, typing and endomyocardial biopsies for macrophage subpopulations is a sensitive new approach to assess the diagnosis of myocarditis.

Surgically-obtained tissue specimens from 41 patients with ventricular aneurysm were studied electron microscopically. The tissue from the resected aneurysms showed substantially varied morphological differences. In some, there were extensive regions of scar containing increased fibrotic material and few cells, in others there were also larger contiguous regions of myocardium with an essentially normal appearance. In the preserved myocardial regions, the cardiac cells showed moderate hypertrophy. There was an increase in contractile substance in parallel with an increase in mitochondria and enlargement of the nucleus with frequent waves and invaginations in the cell membrane. The cells at the marginal regions between fibrous tissue and preserved myocardium were frequently isolated from adjacent cells. In particular, when the isolated cells were completely surrounded by fibrous tissue, clear degeneration was apparent. These cells showed mainly a fibrillolysis with dissolution of the cross-bands and loss of the entire contractile apparatus. In compensation, occasionally there was proliferation of other cell structures, especially the free sarcoplasmatic reticulum. The hypertrophy of the still intact myocardial cells is considered compensatory for the infarct-incurred loss of tissue. The degenerative appearance is mainly attributable to fibrous tissue invasion. The diminished oxygen supply, compromised or abolished impulse conduction, loss of function and passive stretch during systole may be regarded as causes of the degeneration.

Fully developed cyclophosphamide-induced cystitis is characterized by nearly complete detachment of the urothelium, severe submucosal edema owing to damage to the microvascular bed and focal muscle necroses. The initial response to the primary attack by the cyclophosphamide metabolites seems to be fragmentation of the luminal membrane. This damages the cellular barrier against the hypertonic urine. Subsequent breaks in the lateral cell membranes of the superficial cells and in all the plasma membranes of the intermediate and basal cells, intercellular and intracellular edema and disintegration of the desmosomes and hemidesmosomes lead to progressive degeneration and detachment of the epithelial cells with exposure and splitting of the basal membrane. The morphological changes of the endothelial cells, which become more pronounced in the later stages of the experiment, the involvement of blood vessels regardless of their diameter and the location-dependent extent of the damage indicate a direct type of damage which is preceded by a mediator-induced increase in permeability, the morphological correlate of which is the formation of gaps in the interendothelial cell connections on the venules. These changes can be effectively prevented by mesna. The only sign of a possible involvement is the increase in the number of specific granules with a presumed lysosomal function in the superficial cells.

Ultrastructural changes in the tubular epithelium of the rat kidney following a large dose of estrogen (300μg per week for 20 weeks) were studied by means of electron microscopy.

The spontaneous mammary tumors of the NMRI mouse are well developed microcystic adenocarcinomas. Serial isologous transplantation of the tumors results in nearly complete dedifferentiation to a solid tumor, in which only electron-microscopically ru-dimentary acinus-like microlumina can be observed. The adenocarcinomas produce A and B particles in abundance, with the A particles appearing intracellularly in the adluminal cytoplasmic regions of the epithelial cells in association with typical cellular structures and the B particles being restricted to closed extracellular compartments such as vacuoles or acini alone. The loss of alveolar organization in the solid tumors is followed by an almost complete reduction in mature B particles, while A particles are still regularly observed and appear to be less reduced in number. This suggests that the production of extracellular B particles is dependent upon the secretory activity of the tumor cells and that in nonsecreting cells it is predominantly a late step in virus release that is inhibited, not the synthesis of intracellular precursors.

This study investigates the effect of cytochalasin B at a dosage of 0.2 mg per mouse per day for a period of 7 days in an in vivo experiment on mouse liver. Using thin-sectioning and freeze-fracture technique both quantitative and qualitative analysis was made of membranes and cell contacts (gap and tight junctions). Significant alterations of both membranes and junctions were observed. The intercellular space showed vacuolar dilatation in some cases and there were vacuoles observed within the cytoplasm. The microvillar bile canaliculi were dilated. However, no colloidal tracer was observed within the lumen following lanthanum perfusion. With the aid of the freeze-fracture method it was possible to demonstrate that the strands of the tight junctions were highly disorganized. In some cases reduction and in other cases proliferation of tight junctions was observed. Large, proliferative plaques of tight junctions were found both in contact with the tight junctions of the bile canaliculus and ending freely on the plasmalemma. The gap junctions appeared enlarged as well. Their average size increased from 0.42 micron 2 to 0.90 micron 2 (p less than 0.005). The enlargement was also accompanied by an increase in the proportion of the plasma membrane occupied by the junctions: 3.42% in control animals, 10.25% in the livers of mice treated with cytochalasin B. Frequently evaginated and internalized gap junctions were seen in the experimental group. In view of the fact that cytochalasin B, in addition to other effects, also has an effect on the microfilament system of the cell, it may be supposed that microfilaments play a role in maintenance of the orderly structure or in the formation of tight and gap junctions. This remains hypothetical, however, and additional studies are necessary in order to conclusively clarify this issue.

The effect of β-pyridylcarbinol on mice was investigated in long-term studies (21 days, daily dose of 0.1 mg) making use of thin-sectioning and freeze-fracture techniques. Thin sectioning merely revealed only subtle pathological changes including dilatation of the intercellular space and formation of hepatocytic vacuoles. Only upon investigation using freeze-fracture was it possible to demonstrate more profound alterations, primarily involving the cell contacts, i.e. the gap and tight junctions.

Treatment of male Wistar rats with estradiol valerate induced alterations in hepatic gap junctions as visualized by the freeze-fracture technique. The alterations involved the spacing, and regularity of packing of the membrane particles of the P face (PF) and complementary pits on the E face (EF), as well as internalization and changes in the number, size and shape of the junctional domains. In approximately 20% of the PF's of the lateral membrane of treated animals the nonjunctional IMPs were aggregated, while the bile canalicular membrane was never involved, maintaining its random distribution of particles. It is proposed that the changes in junctional area and the more general arrangement of the junctional particles may indicate a decrease in coupling between hepatocytes. The invaginations of gap junctions may represent a means for removing gap junctional membrane from the surface or may be an expression of a higher turnover of gap junctions. We assume that the alterations observed here are due to the specific effects of estrogen. This study addresses in detail a number of possible sites of activity and modes of action for estrogen.