The purpose of this study is to clarify the correlation between the low density areas and periventricular lucency (PVL) on CT and the histopathologic changes of chronic ischemic lesions in cerebral white matter. Thirty seven brains from chronic cases with stroke and 17 brains from patients who showed PVLs on CT were examined histologically. CT scans were performed using GE CT/T. Chronic ischemic lesions with severe demyelination or diffuse cavitation were detected as low density areas on CT. But if associated with severe gliosis, those lesions could not be detected on CT. Areas with myelin pallor could not be detected on CT. In some cases diffuse ischemic lesions as demyelination and cavitation were found in the areas corresponding to PVLs on CT. However, they were not always expressed on CT. Other cases with PVL had no histological changes in the frontal white matter. In conclusion, chronic ischemic lesions in the cerebral white matter could not always be detected as low density areas on CT. This may be partly because decreased density due to demyelination and cavitation was counterbalanced by severe gliosis which tends to increase the density. In some cases PVLs were related to diffuse ischemic lesions in the frontal white matter, but this was not always the case.
By numerous investigators it has been shown that the percentage of lymphocytes having or losing one or more chromosomes increases with age, in cultures of peripheral lymphocytes. Several studies have suggested that acceralated aging process of central nervous system may play a role in etiology of senile dementia. Based on this hypothesis, it has been reported that the percentage of hypodiploidy in senile dementia is significantly higher than that of control group. The purpose of the present study is to estimate the percentage of hyperdiploidy in cultures of peripheral lymphocytes of patients with Alzheimer's disease, which is now pathologically considered an identical disease entity as senile dementia. Besides on this cytogenetic study, radiological, psychological and electroencephalographic evaluations have been carried out and thus correlations among them are also to be discussed. Five male patients with Alzheimer's disease are studied in this investigation. The percentage of hyperdiploidy is estimated as the ratio of number of cells with 47 chromosomes to number of cells with 46 chromosomes. The distribution of extra chromosomes is also shown. For the radiological evaluation of brain atrophy associated with dementia, brain tissue and CSF spaces in three computed tomographic sections are estimated in cm2 by an application computer to avoid the difficulty of visual definition of ventricular borders in planimetric measurement on Polaroid pictures. It has been reported that brain tissue and CSF spaces correlate well with clinical severity of dementia and with scores of several intelligence scales for the aged. Hasegawa's Dementia Scale, BenderGestalt Test and Kohs' Block Design Test are employed for the assessment of cognitive ability of patients. Also, clinical severity of dementia is divided into three categories and dominant frequency of background activity of EEG recordings is checked. The percentage of hyperdiploidy is 2.3% and it is significantly higher than that of the healthy aged. Extra chromosomes most frequently belong to C group and it is suggested that they are most likely to be X chromosomes. Statistically significant correlation is found between the percentage of hyperdiploidy and scores of Hasegawa's Dementia Scale. No correlations are shown between the percentage of hyperdiploidy and other cognitive tests, CT variables and EEG findings. The percentage of aneuploidy, its mechanism and the significance in aging process and age-related dementia have been briefly overviewed. The possibility that the percentage of hyperdiploid cells with 47 chromosomes could be one of significant predictors of cognitive dysfunction in age-related dementia is discussed.
The present study aimed to clarify the relationship between the anual incidence of cerebro-cardiovascular diseases and the clinical variables such as blood pressure, electrocardiographic findings, fundoscopic findings, serum cholesterol levels and the pulse wave velocity (P. W. V.). Where the cerebro-cardiovasccular diseases were cerebral infarction, cerebral hemorrhage, transient ischemic attack, subarachnoid hemorrhage, myocardial infarction and angina pectoris. The subjects studied were the 68, 684 citizens without the diseases stated above. We knew the development of the diseases by the reply postal cards and verified it by telephoning to the patients or their doctors. The PWV method permits the estimation of the degree of aortic sclerosis in non-invasive manner. The PWV as measured by this method is 6-7m/sec for an intact aorta, and more than 9m/sec for highly sclerotic aorta. A detailed report on this subject was made by Yoshimura and Hasegawa. Out of 68, 684 citizens, 198 subjects were confirmed to have the diseases, after one year. The incidences of each disease were as follows; 64 subjects (33%) developed cerebral infaction; 50 (25%) developed angina pectoris; 36 (18%) developed myocardial infarction; 24 (12%) developed transient ischemic attack; 14 (7%) developed cerebral hemorrhage; and 10 (5%) developed subarachnoid hemorrhage. The mean values of systolic pressure (mmHg) were 148 (132) in the forties, 154 (139) in the fifties, 157 (147) in the sixties and 160 (154) in the seventies in the group with the diseases. Where the values in the brackes are the mean values in the group without the diseases. The mean values of diastolic pressure were 87 (77), 88 (80), 86 (82), and 84 (82) from the forties to seventies. The serum cholesterol levels (mg/dl) were 218 (192), 210 (196), 203 (196) and 202 (195) respectively. The PWV values (m/sec) were 8.0 (7.5), 8.5 (8.0), 9.2 (8.7) and (9.4). All clinical variables showed higher levels or higher incidence of abnormal findings in the group with the diseases than in the group without the diseases. The clinical variables which significantly associated with the development of the particular diseases were as follows; serum cholesterol and ischemic heart disease; systolic blood pressure and cerebral hemorrhage; PWV and transient ischemic attack, cerebral hemorrhage and infarction; electrocardiographic abnormality and ischemic heart disease and cerebral hemorrhage. The incidence rates of abnormal fundoscopic finding were the same among all these diseases. We would like to propose that PWV is a usefull method for the multivariate analysis of the risks of these cerebrocardiovascular diseases, as well as the conventional clinical variables.
Age changes of the livers of native Japanese autopsied during 1965-1976 (group-B), have been compared with those of native Japanese autopsied during 1950-1960 (group-A), and Hawaii Japanese. In case of the subjects under 39 years of age, number of hepatic cells in the group-B was similar to that in the Hawaii-Japanese and larger than that in the group-A, but in the older individuals, up to the 70 years of age of the group-B, the number was smaller than in group-A, although weight of the liver was larger in the former than in the latter. Difference in the changing process of the hepatic cell number among the three groups was discussed with reference to the age change of size of hepatic cells and nuclei and of number of binucleate cells. The differences among the three groups support our opinion that the environmental, especially nutritional conditions during their earlier life play an important role in the aging process.
The purpose of this study is to determine the medial elastin and collagen content in injured aorta of strokeprone spontaneously hypertensive rats (SHRSP) developed by Okamoto and others as compared with normotensive contrast wistar-Kyoto rats (WKY). The thoratic aortae from 287 subjects aged from 36 to 622 days were obtained (44 WKY and 243 SHRSP). The elastin and collagen, which had been taken from the thoratic aortae, were measured using the microspectrophotometric procedure (MSP method). This method is selected because it is based on the fact that the maximum extinction of elastin, stained using Weigert stain, is 590nm and collagen, stained Van Gieson stain in 563nm respectively. Results: The elastin content in WKY group was 38 to 40V/V% and decreased slightly with aging. In the SHRSP group, the elastin content was 40V/V% or more before the age of 100 days, but decreased markedly after 100 days. At ages of over 200 days, the elastin content was distributed over a range of 20 to 30V/V%. After 200 days of age, the elastin decreased was from 60 to 68% in comparison with WKY group. The apoplexy group of SHRSP was also decreased about 78% in elastin content as compared with non-apoplexy group of SHRSP at ages from 150 to 350 days. The collagen content in WKY group was 30 to 45%E at ages from 50 to 250 days and decreased slightly with aging at ages of 250 days. In the SHRSP group, the collagen was 40%E or more before the ages of 100 days and decreased straightly with aging from 50 to 350 days. There was another group in SHRSP, which was decreased from 42 to 30%E with ages from 300 to 600 days in collagen content. So the progress of collagen with aging in SHRSP group was surely different from in WKY group. Moreover the collagen content in apoplexy group of SHRSP was decreased about 85% as compared with non-apoplexy group at ages from 150 to 350 days. The changes of elastin content was paralleled to collagen content (correlation coefficient 0.614) with any age in SHRSP. It was proved that the elastic network and collagenous meshwork were destructed with decreasing elastin and collagen of aortic media in SHRSP group by hypertensive factor.
The effect of aging on urinary kallikrein excretion (UkalV) was investigated in normal subjects (n=54, 11 to 88 y.o.) and patients with essential hypertension (n=37, 17 to 82 y.o.). Urinary sodium (UNaV), potassium (UKV), creatinine (UCrV) and aldosterone excretion (UAldV) were also measured in these subjects. UNaV and UKV were not significantly changed with age in both normal subjects and hypertensive patients. In normal subjects, UKalV (r=0.45, p<0.001), UAldV (r=-0.58, p<0.01) and UCrV (r=-0.40, p<0.005) significantly decreased with age. UKalV was positively correlated with both UAldV (r=0.44, p<0.001) and UCrV (r=0.56, p<0.001). In contrast the hypertensive patients showed significant decrease with age in UAldV (r=-0.36, p<0.05) and UCrV (r=-0.44, p<0.01), but no significant change in UKalV and no significant correlation between UKalV and UAldV or UCrV was observed. In the subjects below 60 years there was no significant difference in the value of UKalV between normal subjects and hypertensive patients, but the hypertensive patients above 60 years excreted more urinary kallikrein than normal subjects of the same age group (p<0.05). In conclusion the age-related decrease of UKalV in normal subjects might be due to the reduced activity of the renin-angiotensin-aldosterone system and renal blood flow caused by aging. It remains elucidated whether the absence of the age-related decrease of UKalV in hypertensive patients is related to the pathogenesis or pathophysiology of essential hypertension.
The incidence of atrial fibrillation among 1, 000 consecutive autopsy of the aged more than 60 years was 16.9% (169 among 1, 000), consisting of 73 cases of persistent atrial fibrillation and 96 cases of transient atrial fibrillation. Underlying diseases of persistent atrial fibrillation were (1) valvular heart disease, (2) hypertension, and (3) sick sinus syndrome, and precipitating factors of transient atrial fibrillation were (1) infection, (2) metabolic disorders (hypokalemia, acidosis etc), (3) pericarditis, (4) acute myocardial infarction, and (5) terminal states. Atrial volume was enlarged in persistent atrial fibrillation more than those of transient atrial fibrillation; that is 82ml vs. 47ml in left atrium, 76ml vs. 43ml in right atrium, and 158ml vs. 89ml in both atria. Transient atrial fibrillation from normal sized atrium shows that the atrial size is not the absolute condition of the induction of atrial fibrillation. Atrial volume does not correlate with duration of atrial fibrillation, indicating the enlargement was not the result of persistence of atrial fibrillation, but rather the condition of maintenance of fibrillation. Atrial volume correlated with cardiothoracic ratio (r=0.49) and heart weight (r=0.53).
Wistar rats, kept long on the metal mesh for exprimental uses, cause ulcerative granulomatous lesion at the foot pad. Pathogeneses of these lesion were investigated chiefly from morphological points of view. These lesions never occurred in young. High incidental periods were during 14 to 16 months after birth. One of the most important causative factors was overloading stimmuli by body weight and its traumatic effects against rats' foot pads. At first these lesions appeared at the fourth or fifth metatarsal. By observations of the morphological procedures such as angiography, blood vessel casts, densitometry and so on, these parts of rat were found out to be very poor at blood vessels and other soft tissues. In young periods rats could presumably resist to the mechanical stimmuli to prevent tissue injury, but by aging repeated longstanding loads to foot pad by body weight would finally lead to cause ulceration. Pathohistologically these granulomatous lesions were in principle non-specific one. But capillary blood vessel formation and mitotic activity of connective tissues was so remarkable for their age that it was often severe to differentiate them from neoplasm. These animal models of human disease will be available for the foundamental studies on search for the mechanism of the ulcerative lesions often encounter with such disease as central or peripheral nervous system, occlusive blood vessels or diabetes mellitus.
Serum from old subjects includes immunosuppressive factors which inhibits lymphocyte responsiveness to mitogen without detrimental effects on the viability evaluated by Trypan blue dye exclusion test. In the present study we have attempted to elucidate mechanisms of the inhibitory effect of serum from old subjects on lymphocyte responsiveness to mitogen. Peripheral blood lymphocytes from young persons were stimulated with phytohemagglutinin, concanavalin-A or pokeweed mitogen each for 24, 48 or 72hr. Lymphocyte responsiveness to mitogen was evaluated by thymidine incorporation and uridine incorporation in the lymphocytes cultures. Lymphocyte responsiveness to mitogen was lower in the culture containing serum from old subjects than that result in the culture containing serum from young subjects. Serum from old subjects inhibited lymphocyte responsiveness to mitogen even when the culture period was as short as 24hr. Degree of the inhibition was similar among the results in the 24, 48 and 72hr lymphocytes cultures. Peripheral blood lymphocytes from young persons were stimulated with phytohemagglutinin or concanavalin-A for 72hr in medium containing a small quantity of serum from young subjects at initiation of culture. Serum from young subjects, old subjects, hepatoma patients or pregnant women was added to the culture at various times after iniciation of culture. Thymidine incorporation in the lymphocytes culture with serum from old subjects, hepatoma patients or pregnant women was compared with the results in the culture with serum from young subjects. Serum from old subjects inhibited thymidine incorporation even when the serum was added as late as 67hr after initiation of culture, that is, just before pulsing with 3H-thymidine. This inhibitory effect was not influenced by the time of introduction of the serum. Serum from hepatoma patients or pregnant women profoundly inhibited thymidine incorporation when the serum was added at initiation of culture. However, the inhibitory effect of serum from hepatoma patients disappeared when the serum was added 24hr after initiation of culture, and the inhibitory effect of serum from pregnant women also disappeared when the serum was added 48hr after initiation of culture. These results indicate that serum from old subjects inhibits lymphocyte responsiveness to mitogen in a different way to serum from hepatoma patients and pregnant women. Serum from old subjects inhibits the process of ongoing RNA and DNA synthesis in mitogen activated lymphocytes throughout the entire culture period, in contrast with serum from hepatoma patients or pregnant women which exerts inhibitory effect on the early stage in lymphocytes culture. Proliferative activity of mitogen-stimulated lymphocytes was evaluated by mitotic cells in metaphase in addition to thymidine and uridine incorporation. Lymphocytes cultures were added with colchicine 5hr before termination of culture and percentages of mitotic cells was counted. Serum from old subjects inhibited significantly an appearance of mitotic cells, though profoundity of the inhibitory effect by serum from old subjects was slightly less than that by serum from hepatoma patients and pregnant women.