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Y Higami

Publications and source records attributed to Y Higami.

50 records · Page 3Linked to original sources
PubMed1994

The growth hormone-releasing hormone-cyclic adenosine-3',5'-monophosphate signal pathway in somatotropes is practically intact during aging.

To elucidate the mechanisms of the impaired pituitary response to growth hormone-releasing hormone (GHRH) in aged animals on a cellular basis, a reverse hemolytic plaque assay was performed on dispersed pituitary cells from young (8-month-old) and old (26-month-old) male F344 rats. The proportion of growth hormone (GH)-plaque forming somatotropes, i.e., actually functioning somatotropes, was reduced in old rats to 50-60% of that in young rats under both unstimulated and GHRH-stimulated conditions. The response of dispersed cells to GHRH, however, seemed to remain unchanged with age when expressed as a percent increase of plaque-forming cells from the basal value. The mean diameter of plaques, which reflects the average amount of GH secreted from a single cell, was not smaller in old rats under either the unstimulated or stimulated conditions. There was also no difference between the two age groups in the frequency distribution of the plaque size of functioning somatotropes. The stimulation by forskolin, a compound that directly activates membrane-bound adenylate cyclase and consequently provokes the cyclic adenosine-3',5'-monophosphate (cAMP) pathway for GH secretion in somatotropes, produced almost the same results as those by GHRH stimulation. It was concluded, therefore, that the impaired response of the pituitary gland to GHRH could be due mostly to a reduction in the density of functioning somatotropes rather than to impairments in steps of the GHRH-cAMP signal pathway in somatotropes .

Aging↗
PubMed1994

Vulnerability to oxygen radicals is more important than impaired repair in hepatocytic deoxyribonucleic acid damage in aging.

BACKGROUND: Many previous reports have shown an age-related increase in DNA damage in hepatocytes. This change is thought to result from alterations in DNA repair capacity, DNA vulnerability to oxygen radicals, or both. EXPERIMENTAL DESIGN: Single-cell gel electrophoresis (comet assay), which measures single-strand breaks/alkali-labile sites in the DNA of individual cells, was used to compare DNA repair capacity and vulnerability to damage in hepatocytes prepared from the livers of young (6 to 11 months) and old (26 to 29 months) male Fischer 344 rats. DNA damage was induced in a portion of the cells by exposure to 882 mM hydrogen peroxide. Comet images (migration distance of DNA (MDD) were assessed at the basal level (before exposure) and at 0, 1, 2, and 4 hours' incubation after exposure. RESULTS: The mean basal values of MDD (MV-MDD) and the proportion of hepatocytes with highly damaged DNA (P-HDD) were found to be significantly higher in advanced age. When cells were challenged with hydrogen peroxide, MV-MDD did not differ significantly between the two groups. Interestingly, however, cellular distribution analysis revealed a larger subpopulation of cells with high DNA vulnerability to hydrogen peroxide in rats of advanced age. Furthermore, both MV-MDD and P-HDD were restored almost to basal level at 2 hours incubation after exposure in cells from young rats, while neither recovered even at 4 hours incubation in cells from old rats. This contrast suggests that there is a significant age-related decline in DNA repair capacity. CONCLUSIONS: The low repair capacity in advanced age depends on a subpopulation of cells showing high DNA vulnerability to hydrogen peroxide. Therefore, an increase in the proportion of hepatocytes exhibiting high vulnerability to oxygen radicals is more important than the deterioration in DNA repair capacity in the age-related increase in DNA damage.

Aging↗
PubMed1993

GFAP expression in the subcutaneous tumors of immature glial cell line (HITS glioma) derived from ENU-induced rat glioma.

In order to evaluate the proliferation and differentiation potentials of ethylnitrosourea (ENU)-induced rat glioma cells, the authors attempted to obtain a cell line that maintains glial features in long-term culture. One of five cell lines cultivated from ENU-induced rat gliomas merited particular interest because of the differentiation of its neoplastic glia. This cell line, designated as HITS glioma, had a polygonal cell body and formed a monolayer with pile-up foci in vitro, in contrast to the other cell lines, which displayed a mesenchymal change through passages. GFAP-positive cells, found in the primary culture, disappeared in the late passages of HITS glioma, as they did in the other cell lines. Galactocerebroside (GC), GD3 ganglioside, and Leu7 were not expressed in the cell lines during culture. Subcutaneous inoculation of HITS glioma into neonatal rats induced tumors with histopathological components mimicking the histopathological appearance of ENU-induced gliomas. The components also had a fraction of GFAP-positive cells. Such findings indicate that HITS glioma cells may be composed of immature glial cells which are able to differentiate into astrocytic cells under certain conditions. Several growth factors which play a role in gliogenesis were used to evaluate the mechanism(s) of proliferation and/or differentiation of HITS glioma. These growth factors did not induce the expression of GFAP and other antigenic expression in HITS glioma, even though some promoted the proliferation of HITS glioma. Although the mechanism involving the astrocytic differentiation of HITS glioma is unknown, HITS glioma may serve as an effective tool in research to evaluate the mechanisms of proliferation and differentiation of neoplastic glia.

Animals↗
PubMed1993

In vivo effects of transforming growth factor-beta 2 in ovariectomized rats.

In vitro studies indicate that transforming growth factor-beta (TGF-beta) has a role in the regulation of bone cell activities. However, little is known about the effects of TGF-beta on bone when it is administered systemically. This study was undertaken to evaluate the in vivo effects of TGF-beta 2 on bone and marrow cells in the ovariectomized rat bone loss model. Female Sprague-Dawley rats, aged 95 days, were divided into 4 groups. Group 1 was sham operated; groups 2-4 were ovariectomized. Groups 3 and 4 received daily injections of 10 micrograms and 50 micrograms of TGF-beta 2/kg body weight, respectively. Groups 1 and 2 received the solvent vehicle. All animals were sacrificed after 35 days. Ovariectomy caused a significant increase in, total mononuclear marrow cells, the number of TRAP positive multinucleated cells formed in culture of marrow cells, and the number of trabecular osteoclasts and osteoblasts. These increases were associated with loss of cancellous bone in the proximal tibia. TGF-beta 2 completely prevented the increase in the number of TRAP positive multinucleated cells, and caused a small but not statistically significant decrease in the number of trabecular osteoclasts. However, TGF-beta 2 had no significant effect on the number of total mononuclear marrow cells and on the loss of cancellous bone due to ovariectomy. We conclude that TGF-beta 2 probably plays a role in the regulation of the proliferation of osteoclast progenitors in bone marrow in vivo. Studies carried out over a longer period are required to determine whether it will modulate the increase in osteoclast and osteoblast numbers that occur in cancellous bone following ovariectomy.

Animals↗
PubMed1993

Diet and the suitability of the male Fischer 344 rat as a model for aging research.

There has been concern about the suitability of the male Fischer 344 (F344) rat as a model for aging research because of the high prevalence of a single disease, severe nephropathy, at advanced ages which confounds the interpretation of an aging study. In a publication from our laboratory, Iwasaki et al. (1988) reported that replacing the casein in our standard semisynthetic diet with soy protein markedly decreases the progression of nephropathy with advancing age in ad libitum fed male F344 rats. In the present study, it is shown that replacing the casein with lactalbumin does not decrease the occurrence of severe nephropathy in ad libitum fed rats. It is also shown that dietary restriction (DR) studies can be effectively executed in the male F344 rat when soy protein is the source of dietary protein. It is further shown that when the energy intake of the rats fed soy protein-containing diets was reduced to 60% of the ad libitum intake, almost one-third of the rats died with an absence of severe morphologic lesions, that is, lesions which contribute to the death of the rat. It is concluded that the male F344 rat is an excellent model for aging research when soy protein is the source of dietary protein; no single disease process was found to be primarily responsible for death with such a diet.

Aging↗
PubMed1993

Dietary restriction retards onset but not progression of leukemia in male F344 rats.

The objective of this study was to determine the effect of dietary restriction on the spontaneous occurrence and the progression of leukemia in male F344 rats. The analysis involved both sacrificed rats and those that died spontaneously. These rats had been either ad libitum fed (AL) or restricted to approximately 60% of the ad libitum intake (DR) from 6 weeks of age. Dietary restriction delayed spontaneous death due to this disease by delaying the occurrence of leukemia. However, dietary restriction did not retard its progression, i.e., the time between occurrence and death.

Age Factors↗
PubMed1991

Intravascular malignant lymphomatosis: a case of T-cell lymphoma probably associated with human T-cell lymphotropic virus.

Intravascular malignant lymphomatosis (IML) is an unusual condition characterized by proliferation of lymphoma cells exclusively within the blood vessels. Most of the cases reported are of B-cell origin. We report a rare case of T-cell IML probably associated with human T-lymphotropic virus (HTLV-1) infection. The present case suggests that T-cell lymphoma and HTLV-1-associated lymphoma occasionally represent a form of intravascular proliferation.

Aged↗
PubMed1990

[Incidence of multiple myeloma in Nagasaki City, with special reference to those subjected to atomic bomb exposure].

In order to observe the incidence of multiple myeloma in the population of Nagasaki City from 1973 to 1982, and to assess any influence caused by A-bomb exposure, 85 cases of myeloma have been collected and analysed. Informatively, 48 cases of this number were A-bomb survivors. Among the middle-aged cases, the crude incidence rates of myeloma in the exposed group were found to be higher than those in the non-exposed group. Further, the relative risk of myeloma was higher in A-bomb survivors and this tendency become more pronounced in the those who were within 2 km of the epicenter of the blast. The age-adjusted relative risk in male and female A-bomb survivors was 1.59 and 1.68 respectively, but no significant differences were noted.

Adult↗
PubMedDate not supplied

Physical activity as a factor in the action of dietary restriction on aging: effects in Fischer 344 rats.

Dietary restriction (DR) slows the rate of aging in laboratory rodents but the mechanism of action is unknown. DR is known to induce beneficial effects in a variety of tissues and organ systems. DR also maintains high levels of physical activity over the life span. We tested the hypothesis that lifelong physical activity is an important component of the anti-aging action of DR. Male specific pathogen-free Fischer 344 rats were divided into 4 groups at 6 weeks of age: A: fed old libitum; AE: fed ad libitum and in cages with running wheels; B: fed 60% ad libitum; BE: fed 60% ad libitum and in cages with running wheels. Running activity and spontaneous cage activity were measured over 24 hours and over the life span. Metabolic rate was measured indirectly by analysis of air entering and leaving cages. AE rats exhibited low levels of running activity and ran very little beyond 6 months of age. In contrast, BE rats sustained high running levels even after all A and AE rats had died. High levels of wheel running did not decrease spontaneous cage activity. Median life span (50% survival) was in the order A = AE < B < BE. Ten percent survival was in the order A = AE < B = BE. BE rats had greatest median life span and also highest specific metabolic rate. Exercise and DR altered pathology: At death BE rats had a high incidence of cardiomyopathy, whereas A and AE rats had high incidence of chronic nephropathy and pituitary tumors. The data indicate that increased physical activity is probably not an important factor in the action of DR on aging.

Aging↗
PubMedDate not supplied

Age of onset and type of Japanese younger diabetics in Tokyo.

The age of onset of diabetes and the type of diabetes were examined in 1408 Japanese patients who were initially diagnosed as having diabetes under the age of 30 and were registered in our Diabetes Center between 1980 and 1989. Of the 1408 patients, 538 (38.2%) had insulin-dependent diabetes mellitus (IDDM) (male/female ratio of 2:3), and 870 (61.8%) had non-insulin-dependent diabetes mellitus (NIDDM) (male/female ratio of 5:4). There were significant differences of the sex ratio in both IDDM and NIDDM. The age at which the numbers in both the IDDM and NIDDM groups were almost equal was 13-14 (26 for IDDM and 23 for NIDDM at 13; 28 for IDDM and 30 for NIDDM at 14). A total of 58% of IDDM patients (22% of all patients) and only 6% of NIDDM patients (4% of all patients) were diagnosed under the age of 14 (P less than 0.01). Of the patients with IDDM, 42% (16% of all patients) were diagnosed over the age of 14, as were 94% of NIDDM (58% of all patients). The percentage of NIDDM cases increased even more over the age of 28, and no NIDDM patients developed diabetes under the age of 9.

Adolescent↗
PubMedDate not supplied

Morphometric analysis of somatotrophs: effects of age and dietary restriction.

We investigated changes in the cell number of somatotrophs in the anterior pituitary of male F344 rats caused by age and lifelong dietary restriction (DR). Morphometric and immunohistochemical techniques were performed on the pituitary gland at 6, 18, and 24 months of age. In ad lib fed (AL) rats, cell density of somatotrophs progressively decreased with age. However, when normalized according to the increased volume of the anterior lobe, which occurs during aging, the total number of somatotrophs remained constant until 18 months, then decreased. In contrast, the cell density of DR rats was not affected to the same extent as that of AL rats, and the total number of cells seemed to remain constant through 24 months, thus, retarding the age-related numerical changes. However, the cell number in DR rats, when normalized by body weight, was larger than that found in AL rats. We also found that average cell volume of somatotrophs shows little age or dietary restriction effects, but the nucleus volume significantly increases at 24 months in both groups. The numerical changes which occur in somatotrophs during the aging process may be associated with the aging phenomena found in GH secretion.

Aging↗
PubMedDate not supplied

Malignant peripheral nerve sheath tumors developing multifocally in the central nervous system in a patient with neurofibromatosis type 2.

We describe autopsy findings of multifocal malignant peripheral nerve sheath tumors (MPNSTs) appearing in the central nervous system in a 45-year-old Japanese female with neurofibromatosis type 2. Multiple MPNSTs were detected in both III and VIII, left IV, and V cranial nerves, and a number of nerve roots of the spinal cord. Neurofibromata were on the other hand evident on some nerve roots of the spinal cord and femoral and sciatic nerves. Our results suggest that a mutation of p53 gene may have played a role in the malignant transformation of nerve tumors in this patient since p53 protein was immunohistochemically detected in MPNST cells but not in tumor cells of the neurofibromata.

Fatal Outcome↗