Serum total cholesterol (TC) and triglyceride (TG) were measured in 1739 healhy male employees (age: 20-59 yrs.) in a work-site in Kumamoto, Japan TC and TG were analyzed by AutoAnalyzer method, as our laboratory is a participant of the Cooperative Cholesterol Standardization Program (Atlanta, Georgia, U. S. A.). The procedures are as follows: 1) The individual TC and TG were adjusted to those of age 40. The age adjusted TC and TG out of mean±3 standard deviation (TC>275.6, or<68.2, TG>460, or <44.9mg/100ml) were rejected as probably abnormal. The rejected cases totaled 30, made up 15 higher in TC, 10 higher in TG, one higher in both, 3 lower in TG, and one lower in TC. 2) The 658 cases with ponderal index higher than 1.09 were rejected to eliminate the effect of obesity on serum lipid levels. The cumulative frequency distribution curve of the TC and the Log10 TG of the remaining 1068 cases were linear on normal probability papers up to 85th and 90th percentile, respectively. The 99th percentile values obtained by computer FACOM 230-25 were 251 in TC and 302mg/100ml in TG. When the 99th percentile values were adopted as criteria of hyperlipemia in the population studied, the number of cases of hypercholesterolemia, hypertriglyceridemia, and combined hyperlipemia were 41 (2.35%), 53 (3.05%) and 8 (0.46%), respectively. Those who had TC higher than 300mg/100ml totaled 5 cases. The TC values were 321, 339, 320, 311, and 316. Although the TC values quantitatively correspond to the criteria of hyperbetalipoproteinemia Type II described by Fredrickson, xanthoma was not detected in any of the subjects. The 90th percentile value of TG was 200mg/100ml and very much higher than the upper limit of normal Americans reported in the literatures. Since the TG level of the Japanese reported in the literature in early 1960's were much lower than those from western countries, the elevated TG levels in the population deserve much attention. Preliminary studies of serum lipid levels of urban and rural inhabitants of Kumamoto prefecture revealed no remarkable difference between these groups and the population studied. Excessive intake of high-carbo hydrate diet relative to physical activity is considered one of the factors which elevate serum triglyceride concentration observed in the inhabitant of Kumamoto prefecture, Japan.
Comparison between autopsy diagnosis and clinical diagnosis for cerebrovascular diseases was made to elucidate tendency of physician's diagnostic habit in this country. Age, sex, occupation, clinical diagnosis, and pathological diagnosis of major or minor lesion for each case reported from university hospitals or other principal hospitals in the whole country were available in “Annual of the Pathological Autopsy Cases in Japan” edited by Japanese Pathological Society. Among the autopsied with cerebrovascular disease as a major lesion, those in which cerebrovascular disease occurred as complication of such diseases as trauma, inflammation or malignant neoplasms of brain, valvular heart disease and hematologic or hematopoietic diseases were excluded from the present analysis. Moreover, the range of age was limited to 30 years and over in both sexes. During three year period from 1958 to 1960, 263 or 70.5 per cent of 373 cerebral hemorrhages verified by autopsy, 116 or 37.3 per cent of 311 cerebral thrombosis or infarctions, and 56 or 47.9 per cent of 117 cerebral aneurysms, or subarachnoid hemorrhages were correctly diagnosed clinically as a type of stroke. Seventy five or 20.1 per cent of cerebral hemorrhage as a major pathological lesion, 112 or 36.0 per cent of cerebral infarction and 24 or 20.5 per cent of subarachnoid hemorrhage were diagnosed as cerebral apoplexy or hemiplegia, undetermined type of cerebrovascular disease. Ten years later, from 1968 to 1970, 1, 036 or 69.7 per cent of 1, 487 cerebral hemorrhages, 826 or 50.4 per cent of 1, 638 cerebral infarctions and 404 or 65.1 per cent of 621 subarachnoid hemorrhages were also correctly diagnosed. Two hundred and forty four or 16.4 per cent of cerebral hemorrhage, 551 or 33.7 per cent of cerebral infarction and 84 or 13.5 per cent of subar achnoid hemorrhage were diagnosed as apoplexy or hemiplegia, unspecified type. The change in reliability of clnical diagnosis for cerebrovascular diseases for these ten years was statistically significant in cerebral infarction and subarachnoid hemorrhage (P<0.01). After dividing into two age groups, comparison between autopsy and clinical diagnosis for cerebrovascular disease showed that the improvement in clinical diagnosis was statistically significant in only the old age group (60 years and over) for cerebral infarction (P<0.01) and in the middle age group (30-59 years) and the old age group for subarachnoid hemorrhage (P<0.05 and P<0.01). Although the frequency of diagnosing, cerebral hemorrhage as subarachnoid hemorrhage was 4.6 per cent in the former three year period and 9.1 per cent in the later one, showing significant increase (P<0.01), that of diagnosing cerebral infarction as cerebral hemorrhage was 23.8 per cent and 14.2 per cent respectively, showing declining trend (P<0.01), as well as in diagnosing subarachnoid hemorrhage as cerebral hemorrhage. In nine districts of the whole country, the above mentioned improvement in diagnostic level of cerebral infarction was confirmed with only one exception and no difference was found between the rural areas and the urban areas.
On the Ammon horn from 100 autopsied brains of the aged, an investigation about the Hirano bodies (eosinophilic rod-like structure) was performed by the methods of conventional histology, histochemistry and electron microscopy for the formalin-fixed material, including the tilting method (top-entry type, BLG, of JEM 100B elecron microscope). The results were as follows: (1) Hirano bodies were observed in the nerve cell cytoplasm or neuropil of the pyramidal layer of Sommer sector. They were found in 46% of the examined cases and appeared parallel with increasing age. (2) They were observed frequently together with other senile changes, such as Alzheimer neurofibrillary tangles, granulovacuolar degeneration and senile plaques. (3) Cases with severe dementia showed abundant Hirano bodies. These had no relationship with other basic diseases of the patients. (4) Histologically Hirano bodies were eosinophilic, stained red by Masson-trichrome, black by phosphotungustic acid hematoxylin and showed no argentophilia. They were positive with protein, weak positive with lipid and negative with carbohydrate and mucopolysac charide reactions. (5) Electron microscopically Hirano bodies were composed of regularly arraged cross-lattice of 100Å filaments as a basic structure, which appeared as beaded filaments, lattice or sheets, according to the angles of sectioning. Hirano bodies are thought to be a phenomena of senile changes of the neuron, but their mechanism of genesis is not clear and further investigation is necessary
Senile amyloidotic changes of the brain were investigated in 146 consecutive autopsy cases over the age of 49 years (ranging from 50 to 92, with mean 73.3 in years). The subjects had been admitted to the Department of Geriatrics, University of Tokyo Hospital and Harunaso Hospital (Gunma Prefecture) for chiefly physical diseases. The hippocampus and adjacent areas of the left hemisphere were cut into 6μ-thick specimens after formalin fixation and paraffin embedding, to be examined first by thioflavine T fluorescence microscopy (Saeed and Fine), and subsequently by Congo-red polarizing microscopy (Missmahl). Amyloid in the brain, like in other organs, gave unequivocally strong bluish-white fluorescence through ultraviolet (365mμ) or whitish-yellow through blue light (410mμ) after thioflavine T staining, and also produced green birefringence after Congo red staining. The results were confirmed by other classical stains. Degenerative changes of amyloid nature included: (1) Alzheimer's neurofibrillary changes, (2) central cores of senile plaques, (3) amyloid degeneration of the vessels (amyloid angiopathy), and (4) amyloid infiltration to the perivascular tissues. Alzheimer's nourofibrillary changes, which were seen in 118 patients (81%), were fully and equally detectable both by fluorescence and polarizing microscopy. They gave entirely the same optic qualities as other amyloidotic changes, despite some controversies on their amyloid nature based on electron-microscopic observations. Various forms of senile plaques including so-called primitive plaques were easily detected by fluorescence microscopy because coronas as well as central cores produced some degree of fluorescence. Although amyloid usually existed only in the cores, there were exceptionally two types of senile plaques containing amyloid in other locations, one the plaques with diffuse amyloid deposition also in the coronas, and another the reticular plaques without cores with fiber-or clublike components of amyloid nature. Senile plaques were seen in 58 patients (40%). Amyloid angipathy occurred in the small vessels in the meningeal space and the outer layer of the cortex, most frequently involving arterioles and precapillaries of 100 to 21μ in diameter in the meningeal space, and precapillaries and capillaries less than 50μ in the cortex. In the capillaries amyloid formed semilunar nodules in the walls, finally obstructing lumens. In the arterioles smooth muscle fibers of the tunica media were more specifically involved, beginning with the smooth muscles immediately beneath the tunica adventitia. In several cases with extensive amyloid angiopathy, larger arteries (500 to 1, 000μ in diameter) and veins were also involved. Amyloid infiltration to the perivascular tissues, found in only eight patients, was classified into three types. In the first type, plaque-like structures were formed around the central core of amyloid-deposited capillaries. In the second, typical senile plaques occurred adjacent to the small vessels under amyloid degeneration. In the last rare type, there was diffuse and sparse deposition of amyloid around the small arteries with or without amyloid.
The incidence and quantity of some senile involutional changes in the hippocampal region of the brain was examined in 146 consecutive autopsy cases, with special reference to age, sex and dementia. The subjects, ranging in age at death between 50 and 92 with the mean 73.3 years, had been admitted to the Department of Geriatrics, University of Tokyo Hospital and Harunaso Hospital for chiefly physical diseases (cerebral infarction in 40 patients, myocardial infarction 10, malignant neoplams 24, etc.; unequivocal senile dementia in only 5). The hippocampus and adjacent areas (dentate, parahippocampal, and medial occipito-temporal gyri) of the left hemisphere were prepared into slices of 6μ-thickness after formalin fixation and paraffin embedding, and number of Alzheimer's neurofibrillary changes (NF), senile plaques (SP), the and vessels involved into amyloid angiopathy (AA) was counted respectively over the whole specimen through thioflavine T fluorescence microscopy. (1) Relation of age and sex to the incidence and quantity of NF, SP and AA. The incidence of each change generally rose with age (NF: 29% in 6th decade of age, 59% in 7th, 81% in 8th, and 91% in 9th and above, SP: 12%, 22%, 44%, 56%, and AA: 0%, 7%, 24% 23%, respectively) In each age decade females were usually more frequently affected than males, though the differences were not significant in these small numbers of cases. Quantity of NF, SP and AA was expressed as total counts over the whole specimen of 6μ-thickness, which ranged from 0 to 1, 550 in NF, from 0 to 1, 480 in SP, and from 0 to 330 in AA. When number of each change was graded into 4 levels (0, 1-10, 11-100 and 101-), the occurrence of levels of 11-100 and 101-increased with age both in NF and SP, indicating the age-related increase of NF and SP. The increase of AA was less prominent. (2) Quantitative correlation among NF, SP and AA. Approximate positive correlations in quantity were noted among NF, SP and AA, most markedly between NF and SP, followed by SP and AA, and finally NF and AA. (3) Relationship between the quantity of NF, SP and AA and dementia. Of the subjects examined there were 55 patients whose intellectual capacities had been well-preserved until death (non-demented group), and 61 patients with various degree of dementia (demented group). There was significant difference in the incidence disitribution of the quantity of NF and SP between these two groups (compared after matching age and sex). The comparison of the incidence distribution between severely demented and less severely demented patients, however, revealed no significant difference in the quantity of NF and SP. There was thus a significant difference in the quantity of NF and SP in the hippocampal region between elderly demented and non-demented patients, but no definite correlation was found between the quantity of these changes and the severity of dementia, with the exception of AA.
Pathogenesis of dementia was investigated through quantitative analysis of the involutional changes and the vascular lesions of the brain in 146 consecutive autopsy cases over the age of 49 years (ranging from 50 to 92, with mean 73.3 in years). The subjects, who had been admitted to the Department of Geriatrics, University of Tokyo Hospital and Harunaso Hospital for chiefly physical diseases, were divided clinally into four groups; the demented (61 cases), the non-demented (55), the borderline (19), and the rest (11) in whom insufficient informations were available on the intellectual capacity. As to the involutional changes, number of Alzheimer's neurofibrillary changes (NF), senile plaques(SP), and the vessels involved into amyloid angiopathy (AA) was counted respectively in the 6μ-thick specimen of the hippocampal region through thioflavine T fluorescence microscopy. The patients with involutional changes over certain level (NF≥101, SP≥101, or AA≥1 over the whole specimen) mostly belonged to the demented group (7% of the non-demented, and 60% of the demented). Vascular lesions were examined through serial cutting of the brain, and all the lesions visible to the naked eye were recorded. According to the comparative study of demented and non-demented patients, the important influence of the site, size and numbers of the lesions was evident. Those who showed vascular lesions over a certain level (multiple small lesions or middle- to large-sized lesion (s) in the central region or cortical areas of the left hemisphere) were exclusively included in the demented group (6% of the non-demented, and 58% of the demented). Since mots of the patients with two kinds of the organic changes beyond the extent described above belonged to the demented group except for the border ine cases (13% of the non-demented, and 93% of the demented), such changes probably represent the cause of dementia in the elderly. Thus, 93% (57 cases) of the demented were divided into three subgroups according to their predominant anatomical changes; involutional type(21 cases), vascular type (20), and mixed type(15) consisting of marked degrees of these two. Then clinical data were compared among these subgroups. Of the various manifestations of mental defects (wandering, trifling with feces, hallucinations, night delrium, etc.) none was specific to any one of three types of dementia, except for emotional incontinence which was significantly more frequent in vascular type than in the other two. The frequencies of several neurological signs (diplegia, dysarthria, dysphagia and aphasia) were similar between vascular type and mixed one, and were significantly higher than those in involutional type. Thus, in spite of some similarity to involutional type in some mental features, mixed type resembled vascular type as to several neurological manifestations, indicating a difficulty in clinical differentiation of this type of dementia from the other two.