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I Shimokawa

Publications and source records attributed to I Shimokawa.

At least 55 records · Page 3Linked to original sources
PubMed1994

Immunoelectron microscopic localization of HNK-1 in the embryonic rat heart.

To confirm the role of HNK-1 in conduction tissue, the ultrastructural localization of monoclonal antibody HNK-1 was analyzed in developing rat hearts at embryonal day 14.5 by immunoelectron microscopic labeling procedures with post-embedding immunogold staining. Tissue sections in different planes containing the sino-atrial (SA) node, atrio-ventricular (AV) node and His bundle were used to demonstrate HNK-1. Immunogold labeling was detected on the cell surfaces and in the extracellular matrices of cells that had features common to conduction tissue cells. Non-specialized contractile myocytes were not labeled by this antibody. Furthermore, immunogold labeling was more prominent in wide intracellular spaces than in narrow intercellular spaces, and rarely observed in cell-cell contact regions. The cell surfaces and extracellular matrices of mesenchymal cells in the endocardial cushion, which contacts the His bundle, were also positive, suggesting the involvement of tract formation to the AV node. These findings may indicate that HNK-1 plays an important role in cell-cell adhesion processes both temporally and spatially in the developing conduction tissue. It was concluded, therefore, that HNK-1 is a suitable marker of the embryonic heart conduction system and might be useful in analyzing anomalous conduction systems, as in congenital heart disease.

Animals↗
PubMed1994

Distribution of acetylcholinesterase activity in the rat embryonic heart with reference to HNK-1 immunoreactivity in the conduction tissue.

Acetylcholinesterase (AChE) activity was topographically investigated in the presumptive cardiac conduction tissue regions visualized by HNK-1 immunoreactivity in rat embryos, and AChE-positive cells were examined with the electron microscope. On embryonic day (ED) 14.5, when HNK-1 was most intensely visualized, AChE activity could not be detected enzyme-histochemically in the conduction tissue regions, except in the ventricular trabeculae and part of the AV node. On ED 16.5, however, the AChE activity was clearly demonstrated in some parts of the developing conduction tissue. One exception was the AV node region, where an AChE-positive area was in close proximity to an area showing HNK-1 immunoreactivity but did not overlap. Furthermore, AChE activity was demonstrated predominantly in the ventricular trabeculae, including cardiac myocytes, but was rather weak in the atrium. With the electron microscope, AChE reaction products were observed predominantly intracellularly in both developing conduction tissue cells and developing ordinary myocytes, and no reactivity was found in neuronal components. From ED 18.5 until birth, both AChE activity and HNK-1 immunoreactivity faded away in the conduction tissue. Thus, transient AChE activity in the embryonic heart seems to be different from the developing adult form and may be related to a morphogenetic function in embryonic tissues, as proposed by other authors.

Acetylcholinesterase↗
PubMed1994

Longitudinal study of the hematocrit of ad libitum fed and dietary restricted male F344 rats.

A longitudinal study of age-change in the hematocrit (Hct) was conducted with ad libitum fed and dietary restricted male F344 rats. A progressive fall in Hct occurred over the age range of 3 to 20 months. The magnitude of this decrease in Hct was similar in ad libitum fed and dietary restricted rats. Whether this age-associated decline in Hct continues after 20 months of age cannot be answered with certainty because of the occurrence of diseases at advanced ages which can mask or exacerbate the effects of the aging processes on the Hct. Studies of similar design with males and females of other strains of rats are needed to establish that a decreasing Hct is characteristic of aging in this species.

Aging↗
PubMed1994

An age-related increase in the basal level of DNA damage and DNA vulnerability to oxygen radicals in the individual hepatocytes of male F344 rats.

Previous biochemical studies on pooled hepatocytes have provided a wealth of information concerning age-related changes in DNA damage and DNA vulnerability (susceptibility) to oxygen radicals and related oxidants, but these studies focused on the whole liver and not on individual hepatocytes. The present study was designed to clarify the DNA damage and DNA vulnerability to hydrogen peroxide in individual hepatocytes using single cell gel electrophoresis (comet assay), a method that measures DNA single-stranded breaks/alkali-labile sites in individual cells. Hepatocytes were prepared from the liver of young (6-11 months) and old (26-29 months) male Fischer 344 rats. DNA damage was induced by exposure to hydrogen peroxide (3 x 10(-5), 3 x 10(-3)%). Observation of each comet image (migration length of DNA (MLD)) was performed in a non-exposure status (basal level) and after exposure. The mean value of MLD was significantly increased (approximately 1.5-fold) in the old rats at the basal level (P = 0.009). Moreover, the proportion of highly DNA-damaged hepatocytes (MLD > 80 microns) increased significantly (approximately 2.5-fold) in advanced age (P = 0.02). The mean value of MLD after exposure to hydrogen peroxide was increased with its concentration, but no significant difference was observed in DNA vulnerability to hydrogen peroxide between young and old rats. However, the proportion of hepatocytes showing a markedly high DNA vulnerability (MLD > 140 microns) to hydrogen peroxide was significantly higher in the old rats than in the young rats. It is suggested that the age-related increase in DNA vulnerability to oxygen radicals and/or related oxidants in some subpopulations causes the increase in DNA damage in advanced age in the liver as a whole.

Aging↗
PubMed1994

Duration of dietary restriction: an important determinant for the incidence and age of onset of leukemia in male F344 rats.

The effect of duration and age of initiation of dietary restriction (DR) on the spontaneous occurrence of leukemia was studied in male F344 rats. Four nutritional paradigms were employed: Group 1, ad libitum fed; Group 2, dietary restricted starting at 6 weeks of age; Group 3, dietary restricted from 6 weeks to 6 months of age; Group 4, dietary restricted starting at 6 months of age. The relative incidence (relative onset rate) of leukemia was highest in the rats of Groups 1 and 3 and lowest in the rats of Group 2. The age of onset was earliest in Group 1 followed by Groups 3, 4, and 2 in that order. The progression (duration from onset to death) did not differ significantly between the groups. These results indicate that the duration of DR correlates with the incidence and age of onset of leukemia but not with its progression. The age of initiation of DR is not as important a determinant as the duration of DR in regard to incidence and age of onset. The incidence and the age of onset of leukemia appear to relate to the total cumulative energy intake of the rat (i.e., age multiplied by mean daily energy intake).

Age of Onset↗
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

A case of angiocentric immunoproliferative lesions (angiocentric lymphoma) associated with human T-cell lymphotropic virus type 1.

We report a case of angiocentric immunoproliferative lesions (AILs; angiocentric lymphoma) in the subcutaneous tissue associated with human T-cell lymphotropic virus type 1 (HTLV-1). The patient showed an indolent cutaneous manifestation for 9 years until death. A skin biopsy revealed an angiocentric infiltration of atypical T lymphocytes and a marked coagulative necrosis, which are histologic hallmarks of AILs. Human T-cell lymphotropic virus type 1 antibody was detected by the indirect immunofluorescence test. The proviral integration of HTLV-1 also was confirmed in a DNA extract from paraffin sections using the polymerase chain reaction. The Epstein-Barr virus genome, which has been reported to be associated with AILs, could not be detected by polymerase chain reaction. The present case indicated that HTLV-1 also should be considered one of the pathogenetic factors of AILs.

Aged↗
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↗
PubMed1993

[A case of pulmonary asbestosis with slightly increased serum IgE concentration and histopathological changes resembling DIP].

A 68-year-old male presented with cough and sputum. He had suffered from these symptoms for ten years prior to admission. Chest roentgenogram revealed reticulonodular shadows in the lower fields of both lungs. CT scan of the chest revealed an interstitial pattern in the lower field of both lungs. Honeycombing and bullous pattern were also present in the subpleural area. The patient had a history of dust and asbestos inhalation while working as an electrician. Eosinophilia of the peripheral blood and BALF, and a slightly increased serum IgE concentration were noted. Open lung biopsy revealed interstitial fibrosis with intra-alveolar macrophage accumulation and asbestos bodies. The histopathological features resembled UIP and DIP, although DIP is uncommon in pulmonary asbestosis. The slightly increased serum IgE concentration was considered to be an additional effect of asbestos. This is a case of pulmonary asbestosis with intriguing immunological and histopathological features.

Aged↗
PubMed1992

HNK-1 expression pattern in normal and bis-diamine induced malformed developing rat heart: three dimensional reconstruction analysis using computer graphics.

The spatiotemporal distribution of the immunoreactivity of monoclonal antibody HNK-1 was investigated immunohistochemically in normal and bis-diamine-induced malformed rat embryonic hearts using three-dimensional reconstruction with computer graphics. First recognized in the primitive heart 11.5 days after conception, HNK-1 immunoreactivity was distributed in the atrio-ventricular and bulbo-ventricular junctional areas with incomplete ring-like appearance in the early embryonic stages. In the late embryonic stages the immunoreactive sites were rearranged and localized in the sites topographically corresponding to almost the entire pathway of the conduction system, including the three major internodal tracts connecting the right sinoatrial node and atrioventricular node. Immunoreactivity gradually decreased after the completion of the conduction system, and only a faint reactivity in the atrio-ventricular node region remained in the new-born heart. These results indicate that HNK-1 is expressed temporarily in the pathways corresponding to the conduction system during the development of the heart. In bis-(dichloroacethyl)-octamethylen-diamine (bis-diamine)-induced malformed hearts, localization of HNK-1 immunoreactivity was not remarkably altered in the early embryonic heart. In the late embryo, immunoreactive sites in the sino-atrial node region and atrio-ventricular node region deviated dorsocaudally with the poorly developed internodal tracts, and abnormal distribution was observed in the bilateral atria. We consider that these abnormalities may occur in conjunction with abnormal morphological development such as insufficient absorption of the sinus venosus.

Animals↗
PubMed1992

Immunohistochemical localization of gangliosides in ENU-induced rat glioma.

Biochemical studies have indicated that the structurally simple gangliosides, including GD3 and GM3, are major glycolipid components of glioma tissues. In order to clarify the localization of the gangliosides in ethylnitrosourea-induced rat glioma, an immunohistochemical study was performed using antibodies against GM1, GM3, and GD3. The results obtained in normal fetus, newborn, and adult rat brain, and also in human glioma, were compared. In fetal and newborn rat brain, GD3 was present mainly in the neuroepithelial cell surface of the matrix and subependymal layers of the ventricular wall, but GM3 and GM1 were not detected. In adult rat brain, GD3-positive cells were absent, or present in diminished number, and GM1 was found chiefly in the neuropil of the cerebral cortex. Most of the rat glioma cells were positive for GD3, but not for GM1. It was demonstrated that the ganglioside composition of glioma cells was similar to that of immature neuroectodermal cells in fetal and newborn rat brain. Furthermore, the number of GD3-positive oligodendroglioma cells increased with tumor growth. In anaplastic gliomas and gross oligodendrogliomas, most tumor cells expressed not only GD3 but also GM3. These results suggest that GD3 is a marker of proliferating neuroectodermal cells, and that activity of the key enzymes in ganglioside synthesis alters with tumor growth and anaplastic change.

Adult↗
PubMed1991

Effect of dietary restriction and aging on polyploidy in rat liver.

Liver polyploidy levels were compared as a function of age and diet in male Fischer 344 rats between 1 and 24 months of age. Dietary restriction was imposed on one group by reducing their food intake to 60% of ad libitum food intake. Histological sections of the livers of animals at each age and diet were examined. Diploid, tetraploid and octaploid nuclei were observed, and their size and frequency established. There were no differences in the diameter or volume of these size classes as a function of age or diet. An age-related decline in the percentage of diploid nuclei, coupled with an increase in the percentage of tetraploid and octaploid nuclei was observed in both groups. The major difference between the two groups was that the adult level of liver polyploidy was attained more slowly in the animals on dietary restriction as compared to the ad libitum fed controls. Polyploid cell formation in the liver is under the control of growth hormone, thyroid hormone and thymus, all of which might be influenced by dietary restriction.

Aging↗
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↗
PubMed1991

Influence of diet on fatal neoplastic disease in male Fischer 344 rats.

The influence of dietary manipulations on fatal neoplasms in male Fischer 344 rats was assessed. Particular attention was paid to leukemia and pituitary adenoma because they are the most common potentially fatal neoplasms that occur in this rat strain. The only dietary manipulation which depressed the mortality rates due to neoplastic disease was that involving a reduction in energy intake. Reduction of mineral or protein or fat intake without a reduction of energy had, at most, marginal effects on fatal neoplastic disease.

Adenoma↗