Selective calcification of rat brain lesions caused by systemic administration of kainic acid

Dystrophic calcification of previously damaged areas of nervous tissue occurs in a wide range of human diseases. The relationship between astroglial and microglial reactions and deposits of calcium salts was studied for up to five months in rats with a brain lesion produced by systemic administration of kainate. The morphology and atomic composition of the calcium salt deposits was also studied. Two types of lesions, sclerotic and liquefactive, were observed. In sclerotic lesions hyperplasia and hypertrophy of astrocytes partially substituted for the lost neurons, reaching a maximum in about twenty-five days after treatment. In liquefactive lesions, the astrocytic reaction occurred only around the liquefactive area. Microglial reaction was similar in both types of lesion and reached its highest expression in about twenty-five days. Calcium deposits were observed in the sclerotic but not in the liquefactive lesions. Clearly distinguishable granules of calcium salts were observed in sclerotic lesions under scanning electron microscopy after only five days post-injection. The size of calcified granules increased with time reaching 40 micro m or more in diameter at five months. The atomic composition of these deposits, studied by X-ray microanalysis, showed a time-dependent increase in calcium concentration. While there was no clear relationship between astroglial and microglial reactions and calcium salt deposits, the systemic injection of kainate produced progressively larger and more concentrated calcium deposits in sclerotic, but not in liquefactive lesions.     

Sequence-specific alkali-labile lesions in DNA caused by d-isoglucosamine

The site-specific induction of DNA damage by 1-amino-1-deoxy-d-fructose (d-isoglucosamine) was investigated. When ³²P-end-labeled DNA restriction fragments of known sequence were reacted with d-isoglucosamine in the presence of Cu²⁺, and the DNA products were analyzed on high-resolution denaturing polyacrylamide gels after treatment with aqueous piperidine (1 M) at 90°C for 30 min, the DNA strands were cleaved at pyrimidine residues at a statistically significant frequency, and 80.5% of the extensively damaged sites were induced at pyrimidine residues in dinucleotide sequences of pyrimidine-purine (5′ → 3′). These cleavages were scarcely observed without piperidine/heat treatment. The damaged DNA sites increased in proportion to the reaction time and concentration of d-isoglucosamine. Metal-chelating agents (EDTA, diethylenetriaminepentaacetic acid) and some oxygen radical scavengers inhibited the induction of alkali-labile lesions. These results indicate that some oxygen radicals are involved in the induction of alkali-labile lesions.     

Myocardial cell lesions caused by an anabolic hormone

Summary Early changes in the composition of heart muscle cells of the rat caused by an anabolic hormone were investigated by electron microscopy. Mitochondria and myofibrils showed changes similar to those observed in early heart failure: The mitochondria were swollen and elongated. Their matrix was sparse and the cristae were few in number. The myofibrils showed either disintegration and widened and twisted Z-bands or a complete dissolution of the sarcomeric units.This work is supported by the Deutsche Forschungsgemeinschaft (Be 742/1)     

Experimental infection caused by Issyk-Kul' arbovirus

Experimentally in green monkeys, Syrian hamsters and white mice the authors studied the pathogenic properties of a new virus Issyk-Kul. The virus was determined in all animals--in blood and organs (brain, lungs, liver, spleen, kidneys). During the histological investigation the inflammatory and dystrophic injuries were established: in CNS, lungs, liver and kidneys. There was a distinct immunomorphological reaction in the spleen. The virus has pantropic properties and causes a generalized infection in animals.     

Persistent karyomegaly caused by Penicillium nephrotoxins in the rat.

Continuous or intermittent consumption by rats of food moulded by Penicillium aurantiogriseum induced prominent and extensive histopathological changes within several weeks seen specifically at the renal cortico-medullary junction. Many cells of the P3 segment of proximal tubules contained either giant nuclei or multiple enlarged nuclei, described in this text as karyomegaly, but also included within a cytomegalic change. The changes contrasted with the tubular cell necrosis and concomitant mitosis elicited after only four days consumption of nephrotoxic mould. Unilateral nephrectomy enabled persistence of histopathological changes to be assessed directly after detailed histology at an earlier stage. After ten days consumption of food with a 100-fold excess of fungal extract containing the amphoteric nephrotoxins, the typical acute histopathology evolved, over a period of three weeks on normal diet, into the bizarre karyomegalic histopathology, implying a latent effect. Karyomegaly persisted for at least twelve months after nephrotoxin dosage ceased. P. aurantiogriseum karyomegaly was much more striking than that induced by a relatively high chronic dose of another Penicillium nephrotoxin, ochratoxin A. Although the study does not attempt to measure relative potencies, qualitatively similar ultrastructural changes (enlarged nuclei, proliferation of smooth endoplasmic reticulum and thickening of proximal tubule basement membranes) were induced by the two types of nephrotoxin. The broadly toxic ochratoxin A is the popular putative aetiological agent in the mysterious and insidious Balkan endemic nephropathy and associated urinary tract tumours. As the renal carcinogenicity of ochratoxin A in rats follows karyomegaly, the striking karyomegaly induced by P. aurantiogriseum in the proximal tubules of the kidney must be considered as a potential factor in human chronic renal disease.