Abnormal Glycogen Accumulation Research Articles

Glycogen reaction to cerebral stab wound during maturation of rat brain.

Abnormal accumulation of glycogen around cerebral stab wounds was studied histochemically, electron microscopically, and quantitatively in rats 4, 13, 28 days old and in adult (90–150 days old) animals. Glycogen did not accumulate around stab wounds in 4 and in 13-day old rats, whereas a considerable accumulation of glycogen was present in the 28 day and in adult animals. There was a close parallelism between the amount of glycogen accumulated and the degree of maturation of oxidative enzyme activity as reflected by succinic dehydrogenase activity in the cortex. In 28 day and in adult animals, a pale central necrotic core was surrounded by a zone of reduced enzyme activity. The region of glycogen accumulation was located peripherally to this zone.

Hepatic glycogenolysis induced by glucagon in a patient with type I liver glycogen disease

Direct evidence was obtained, by chemical and isotopic measurements, that glucagon induces active hepatic glycogenolysis in type I liver glycogen disease, at a rate comparable to that observed in normal rats and dogs and, presumably, normal man. This liver glycogen breakdown was associated with no increase in blood glucose, but in a rapid rise of blood lactate. Indirect evidence suggests that the response to endogenous secretion of glucagon is similar. The conclusion that both exogenous and endogenous glucagon exert their usual glycogenolytic effects in this disease but that the end product is lactic acid rather than glucose indicates that (1) the abnormal accumulation of liver glycogen observed in type I glycogen disease is not a consequence of the deficiency in glucose-6-phosphatase per se (2) increased glycogen synthesis must play a major role in accounting for this excessive liver glycogen content.

EARLY HISTOCHEMICAL CHANGES IN PERINATAL ASPHYXIA

1. Histochemical observations were carried out on newborn monkeys delivered by caesarean section at 153 to 163 days of gestation and immediately asphyxiated for approximately 12 minutes. 2. The main histochemical finding consisted in widespread, abnormal accumulation of glycogen in glial cells (predominantly astrocytes) of both gray and white matter, which became conspicuous approximately 10 hours after asphyxia and tended to disappear after several days. Abnormal deposition of glycogen in glial cells was also demonstrated by electron microscopy. 3. Glycogen accumulation was preceded by a marked increase in phosphorylases and UDPG-glycogen transferase activities already demonstrable in animals sacrificed 1 hour after asphyxia. 4. Similarly early was the appearance of abnormal activity of aminopeptidase in neuronal groups which were shown to be especially susceptible to asphyxia and displayed evidence of histopathological damage at later stages. 5. The changes in respiratory enzymes were generally of a nature previously described, and they were characterized mainly by reduction in the activity of individual enzymes in regions of the gray matter which later showed evidence of histopathological damage. 6. Disturbances of the blood-brain barrier were demonstrable in animals sacrificed 10 hours and later after asphyxia. The main feature consisted in selective localization of the tracer in the cellular components of the parenchyma, mainly in the neurons. The changes were confined mostly to the gray matter without any clear correlation to the intensity of the histopathological damage.

GLYCOGEN STORAGE DISEASE OF THE HEART

Two cases of glycogen storage disease of the heart occurring in siblings are reported. The first patient died at the Babies Hospital in 1922 and the diagnosis was established at autopsy. The second patient was admitted in 1948 and died after 33 days in the hospital. The family history reveals that the mother of the two patients had eight other children, of whom two are suspected of having succumbed to the same condition. Detailed clinical, chemical and pathologic studies were carried out on the second patient. Numerous chemical determinations were performed both before and after death. The pathologic changes were characteristic of those previously described in cases of glycogen storage disease of the heart. Despite the name of the disease, the abnormal glycogen accumulation and the consequent altered cellular structure were not limited to the heart, but were found in many other organs and tissues of the body. The chemical data revealed an apparently normal sequence of events in the mechanisms for carbohydrate metabolism that could be investigated. It was therefore hypothesized that the metabolic error lay in an excessive rate of accumulation of glycogen in the tissues. It was suggested that this might be consequent to the formation of a polysaccharide closely allied to glycogen, but differing from it in its chemical structure, or to inability of these patients to transform carbohydrate to fat.