Tsuneko Sato

Selective increase in S-100β protein by aging in rat cerebral cortex

Changes in the cocentrations of nervous tissuerelated proteins and their isoproteins, such as S‐100 proteins (S‐100α and S‐100β), enolase isozymes (α‐enolase and γ‐enolase), and GTP‐binding proteins (Goα, Gi2α, and β‐subunits), were determined in the CNS of male rats of various ages (from 2 to 30 months old) by means of enzyme immunoassay. The weights of brains and the concentrations of soluble proteins in the cerebral cortex, cerebellum, and brainstem were constant during the observation period. The concentration of S‐100β protein, which is predominantly localized in glial cells, increased gradually in the cerebral cortex with age; levels in the 25‐month‐old rats increased to approximately 150% of the levels in the young (2‐month‐old) rats. However, the S‐100β concentrations in the cerebellum and brainstem were relatively constant, showing similar values in rats 2–30 months old. Levels of other proteins, including both neuronal (γ‐enolase and Goα) and glial (α‐enolase and S‐100α) marker proteins, did not change significantly with age in the cerebral cortex, cerebellum, and brainstem. These results suggest that there is a close relation between the age‐dependent changes of the CNS function and S‐100β protein levels in the cerebral cortex.

Concentrations of several proteins characteristic of nervous tissue in cerebral cortex of patients with alzheimer’s disease

Concentrations of nervous tissue-related proteins, including S-100 proteins (α and β), enolase isozymes (α and γ), superoxide dismutase (SOD) isozymes (Cu/Zn SOD and Mn SOD), and GTP-binding proteins (α subunits of GO and Gi2) were determined in the four cerebrocortical regions (superior frontal gyrus of frontal lobe, parahippocampal gyrus of temporal lobe, superior parietal lobule of parietal lobe, and calcarine area of occipital lobe) of patients with Alzheimer’s disease, and age-matched control and young control patients by means of enzyme immunoassay methods. Although the temporal cortex of some patients with Alzheimer’s disease (4/7) showed apparently enhanced S-100β with decreased γ-enolase, concentrations of neuronal (neuronspecific γ-enolase and the α subunit of GO) and glial (S-100β, S-100α, and α-enolase) marker proteins, and both SODs in each region were not significantly different between patients with Alzheimer’s disease and the agematched controls. Concentrations of Gi2α also showed similar values in the cerebral cortices of young and aged controls and patients with Alzheimer’s disease. However, when compared with young controls, S-100β in the four regions of patients with Alzheimer’s disease and aged controls, and Cu/Zn SOD in frontal cortex of patients with Alzheimer’s disease were significantly enhanced (P<0.01).

Extremely Well Differentiated Papillary Adenocarcinoma of the Lung with Prominent Cilia Formation

We describe a 54‐year‐old woman with primary pulmonary adenocarcinoma showing a characteristic papillary architecture and prominent cilia formation. Immunohistochemically, the tumor cells were positive for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and Leu Ml, and negative for lactoferrin and surfactant apoprotein. An ultrastructural study also indicated differentiation toward bronchial surface epithelial cells. To our knowledge, this type of neoplasm has not been reported as peripheral‐type adenocarcinoma of the lung. Acta Pathol Jpn 42: 745–750, 1992.

Quantitation of changes in mitochondrial DNA during aging and regeneration of rat liver using non-radioactive DNA probes

By using DNA probes prepared from cloned cells which contain mitochondrial DNA (mtDNA) sequences in plasmids, the specific detection of mtDNA became possible in the presence of large excess of nuclear DNA by DNA-DNA hybridization. For this purpose, we prepared mtDNA probes labeled with non-radioactive substrate, which allowed a wider possibility of application. This method revealed that the contents of mtDNA in rat liver are strikingly decreased during aging. Furthermore, it was observed that although mtDNA content increased upon partial hepatectomy even in old rats, it decreased to the pre-operation level rather rapidly within 1 week after reaching peak in regenerated liver.

Morphological aspects of aging liver: half a century of progress in Japan

The most important morphological aspects of the physiological changes of the liver with age are decreases in the numbers of hepatocytes and their mitochondria, coupled with increases in their volumes. The latter is considered to partially compensate for the decrease in numbers of hepatocytes and mitochondria, but leads to a more limited reserve capacity and thus to a condition in which liver function can be more readily exhausted. The binuclearity and polyploidization of the hepatocytes increase with age and are considered to be due to inhibition of their cell division process. Our studies on the parabiosis between young and old rats and mice, on the implantation of isolated hepatocytes in the spleens of rats of different ages, and on the regenerative process after partial hepatectomy in rats of different ages, suggested the existence of humoral inhibitory factor(s) for the division of the cells and their mitochondria. Morphological studies on the native and Hawaiian Japanese, as well as on the USA Caucasians and the Costa Rican Latinos revealed that a difference in the process of the age-related decrease in hepatocyte number among different ethnicities is mainly due to differences in nutritional conditions rather than to genetic factors. Experimental studies are now being carried out on the effect(s) of various dietary conditions on age-related changes of the liver, and the results obtained support the findings of the geographical studies.

Breast cancer in English and Japanese women: Prognostic significance of sinus histiocytosis and germinal center hyperplasia in axillary lymph nodes

SummaryA prospective study of comparable Japanese and British breast cancer patients treated by radical mastectomy confirmed previously reported findings that sinus histiocytosis and germinal center hyperplasia are more frequently seen in axillary lymph nodes from Japanese than in those from British patients. In Japanese, but not British, cases of either of these two morphologic findings had favorable prognostic significance for recurrence. Sinus histiocytosis also had favorable prognostic significance in Japanese cases for five year survival. In a separate review of axillary nodes from Japanese autopsy cases sinus histiocytosis was absent, suggesting that this finding in Japanese breast cancer cases was related to presence of the disease.

Comparative histological analysis of British and Japanese breast carcinomas.

Histopathological analysis of several factors was made in an attempt to explain the difference in prognosis after mastectomy for mammary carcinoma in Japanese and British women. The higher age, lower grade of differentiation, and lower sinus histiocytosis and germinal center hyperplasia of the British cases may explain their worse prognosis.

Retroperitoneal leiomyosarcoma of a male centenarian

An autopsy case of retroperitoneal leiomyosarcoma of a centenarial male is described. He complained of abdominal pain In his left side 1 month before his death. Ultrasonog‐raphy and computed tomography revealed a large mass in the left abdominal cavity. At autopsy, a circumscribed mass, 15 cm in diameter, was found in the left‐upper abdominal cavity, and seemed to be derived from the retroperitoneum in an exophytic manner. Histologically, spindle cells with slight eosinophillc cytoplasm and blunt‐ended nuclei showed interwoven fascicular growth, and mitotic figures were easlly encountered. Immunohlstochemically, the tumor cells were labeled by α‐smooth muscle actln and vimentln. To our knowledge, this case of leiomyosarcoma has presented in the oldest patient ever reported. The rarity of soft tissue sarcomas in the extremely elderly is also discussed.

Age-related change in activation by Tris (hydroxymethyl) aminomethane on myosin-ATPase activity of human minor pectoral muscles

Age related change of the human minor pectoral muscles was biochemically demonstrated. Myosin-ATPase activity was significantly decreased with age, and was activated with Tris. The degree of the activation by Tris was observed to be lower in old aged patients than in the young. Furthermore, at low concentration of CaCl2 (less than 100 microM), myosin-ATPase activity was higher in the young age than in the old, while at high concentration of CaCl2 (more than 1 mM) no significant difference was observed between young and old age. Decrease with age in activation by primary amine such as Tris would play an important role in the muscle working capacity in old age.

Parvalbumin expression in the diaphragm of aged rats.

Parvalbumin is a calcium-binding protein involved in the mechanism of Ca(++) exchange between the sarcoplasmic reticulum and the myofibrils. There is a direct correlation between the amount of parvalbumin and the velocity of contraction-relaxation of skeletal muscle fibers. Male Donryu rats (6, 24 and 30 months of age) were housed in a specific pathogen free room and fed with 60% of the mean daily quantity of rodent chow consumed by rats fed ad libitum. To assess the expression of parvalbumin in the rat diaphragm, transversal sections were processed immunohistochemically using polyclonal antiparvalbumin antibody. The stained sections were inspected on an image analysis device to evaluate the intensity of the immunoreaction and to take morphological measurements of the muscle fibers. The optical density data allowed the distinction of fibers in fast- and slow-twitch types. The results show that the number of fibers did not change in young and old rats, but the percentage of muscle fibers containing parvalbumin decreased with age. Moreover, the fast-twitch fibers showed a remarkable decrease in their diameter at 30 months of age, but the slow-twitch ones did not. The results suggest that, as the organism gets old, the fiber type composition of the diaphragm changes to adapt to different physiological and/or metabolic exigencies.