Wataru Mori

Pineal gland in old age; quantitative and qualitative morphological study of 168 human autopsy cases

Age-related changes of human pineal gland were studied morphologically on 168 autopsy cases. Pineal weight in the formalin-fixed condition was 99 +/- 56 mg in males (n = 88, mean age 78 years) and 91 +/- 41 mg in females (n = 80, mean age 79 years), which showed no sexual difference (P = 0.290). There was no correlation between pineal weight and age of the patient (r = 0.0678, P = 0.191, n = 168). The pineal volume calculated as a spheroid was directly proportional to the weight (r = 0.904, n = 167, P = 0.000). A significant correlation existed between pineal weight and the degree of calcification (r = 0.231, P = 0.002, n = 156). The density of the pineals decreased with age (r = -0.164, P = 0.017, n = 167). The degree of calcification and cyst formation did not increase with age, but the grade of cyst formation was related to the pineal volume (P = 0.0002). Some pineals of the patients over 90 years old showed no calcification and appeared indistinguishable from the ones of the younger subjects. The weight and volume of the pineals of the patients with hypertension was appreciably greater than those of the non-hypertensive patients. These results indicate that human pineals do not necessarily degenerate progressively after involution.

A morphological study of the circadian cycle of the pineal gland of the rat

SummaryTo seek a morphological expression of circadian rhythm, we investigated cytologically pineal glands taken from rats every 2 to 4 h under a lighting regime of 12 h of illumination (6:00 to 18:00) and 12 h of darkness. The changes in the number of synaptic ribbons and ribbon fields was observed by electron microscopy. The number of these intracellular elements was greatest at 2:00 and the lowest at 14:00, the difference being statistically significant. There were no significant local differences in numbers with respect to the part of the pineal gland examined. The data are similar to those of Vollrath from the pineal gland of a guinea pig, and seem to confirm a circadian function in the pineal gland in mammals.

ANTI‐GLUCOCORTICOID EFFECTS OF MELATONIN IN YOUNG RATS

Administration of the pineal hormone melatonin to young female rats provided significant prevention of the injurious effects (decrease of body weight gain, atrophy of the thymus and adrenals, glucosuria, elevation of the blood level of glucose, free fatty acid, triglyceride, and total cholesterol) caused by three different glucocorticoids, i.e. dexamethasone, prednisolone, and hydrocortisone. Although these protective effects of melatonin were slightly more remarkable in dexamethasone‐treated rats than in prednisolone‐ or hydrocortisone‐treated rats, our hypothesis of melatonins anti‐glucocorticoid effects is said to have been confirmed rather universally and with a considerably wide range through this experiment.

Cirrhosis and primary cancer of the liver. Comparative study in Tokyo and Cincinnati

A survey of 3,232 autopsies in Tokyo revealed 59 examples of primary hepatic cancer and 124 examples of liver cirrhosis. This result, with emphasis on the interrelationship of these two lesions based on the classification of cirrhosis, was compared with similar findings in a survey made by E. A. Gall in Cincinnati, Ohio, under comparable circumstances. There is an agreement in the fact that significant causative relation exists only between hepatocellular carcinoma and nonspecific cirrhosis. The higher incidence of primary hepatic cancer in Tokyo may be due to the following facts: Types A and B (postnecrotic and posthepatitic) cirrhosis, which may be called hepatoma‐related, seem to be more active in Tokyo: The former shows higher incidence in number, and the latter shows higher possibility of malignant complication. On the other hand, type C (nutritional) cirrhosis, which may be called hepatoma‐unrelated, seems to be more common in Cincinnati.

VICTORIA BLUE‐NUCLEAR FAST RED STAIN FOR HBs ANTIGEN DETECTION IN PARAFFIN SECTION

Hepatitis B surface antigen, in paraffin embedded sections, can be stained by victoria blue and recognized easily against the background, including the cytoplasm and nucleus, stained by nuclear fast red. This new staining method has many merits such as easy staining procedure, long stability of dye solution, negative Rtainability of ordinary bile pigment, etc., and seems to be quite useful for routine as well as research works in hepatology.

Pineal synaptic ribbons in blinded rats

SummaryTo study the effects of bilateral ophthalmectomy on the circadian rhythm of the pineal gland, the number of the synaptic ribbons and ribbon fields in the pineal gland of female rats were determined by electron microscopy. In a preliminary experiment, the pineal gland was taken from rats at 15 days, and 1, 2, 3, 4, and 6 months after bilateral ophthalmectomy. It was found that the numbers of both synaptic ribbons and ribbon fields decreased markedly and reached a minimum at 1 month postoperatively, but recovered completely after 4 months. In the main experiment, the number of these intracellular elements was counted in both control and enucleated animals killed at 4 h intervals between 02:00 h and 22:00 h at either 1 month or 6 months after operation. All animals were kept under a lighting regimen of 12 h of illumination (06:00 to 18:00) and 12h of darkness (18:00 to 06:00). After 1 month, a remarkable decrease in the number of both the synaptic ribbons and ribbon fields was again noted but the circadian rhythm still remained. Complete quantitative and qualitative recovery in the circadian rhythm was obtained 6 months later.

Anti-hypercholesterolemic effect of melatonin in rats.

The effects on plasma lipids of daily intraperitoneal injections of 4mg of melatonin (N‐acetyl‐5‐methoxytrypt‐amine) for 10 27 day periods were examined biochemically and morphologically in rats fed regular and high‐cholesterol (1% cholesterol, 0.5% cholic acid) diets. Melatonin administration had no significant effect on plasma lipids and lipoproteins in the rats on a normal diet but blunted the effects of a high‐cholesterol diet on these parameters. No effects of melatonin on lipase activity were noted. Melatonin also diminished the fatty infiltration in the liver of animals on the high‐cholesterol diet. The high‐cholesterol diet produced major increases in VLDL and LDL cholesterol and protein content, and decreases in HDL cholesterol and protein. Melatonin decreased the extent of this plasma lipoprotein increase, although it did not completely prevent the phenomenon. Therefore, the effect is thought to be quantitative and not quantitative in nature. Acta Pathol Jpn 39: 613‐618, 1989.

FATAL HEPATIC NECROSIS AFTER SHOCK

A clinicopathological study was undertaken in 15 cases of massive hepatic necrosis after shock. The GOT and GPT level exceeded 1000 units in 10 cases. The 15 cases consisted of 3 diagnosed as fulminant hepatitis clinically and 12 diagnosed as disseminated intravascular coagulation (DIC) or multiple systemic organ failure (MOF) from the unremarkableness of liver dysfunction. It was noteworthy that sepsis and surgery were closely associated with these lesions. The weight of the liver at autopsy ranged from 800 to 2,700 g. Liver necrosis was macroscopically characterized by clear demarcation of the necrotic areas sharply separated from the surrounding liver parenchyma, showing the appearance of so‐called “map‐like necrosis”. Microscopically, the lesions in these subjects showed mainly the pattern of centrilobular necrosis. As observed in the burn shock case (case 12), the shock which provoked in different phases of time seemed to have repeated its attack. These liver necroses were considered to result from severe systemic circulatory disturbance or intrahepatic circulatory disturbance. The possibility is indicated that the generalized or univisceral Shwartzman reaction, and repeated and combined severe shock participated in the pathogenesis. Fibrin thrombi aggrevate tissue perfusion and accelerate anoxia. Heparin therapy seemed effective in these cases if administered at an appropriate time.

Effects of melatonin on genetic hypercholesterolemia in rats

Administration of the pineal hormone melatonin to genetically hypercholesterolemic rats resulted in a decrease in plasma cholesterol levels and in an improvement of fatty changes of the liver. Thus, the antihyperlipemic effect of melatonin, which was first discovered in hypercholesterolemia produced by short- or long-term administration of glucocorticoids, has now been proved to be rather universal and not simply anti-glucocorticoidal. The mechanism of the decrease of plasma cholesterol levels remains unknown. It was also found that the pathogenesis of this so-called genetic hypercholesterolemia in rats involved biochemical nephrotic changes and histopathological changes in the kidney.

Extensive Hepatic Cell Necrosis Produced by the Shwartzman Mechanism

Acute, severe, and extensive necrosis of the liver was produced in pregnant and non-pregnant female adult rabbits by the Shwartzman mechanism. Shwartzman reagent (E. coli endotoxin) was administered in various combinations by three routes of injection, the portal vein (mesenteric vein), the bile duct, and the ear vein. Morphologic changes of the extrahepatic organs were minimal. The similarity to massive necrosis in human liver and the effect of pregnancy on hepatic necrosis in rabbit and man were discussed. The lesion is presented as a new animal model for acute massive hepatic necrosis and is proposed as a third category of Shwartzman reaction, designated the univisceral type.