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Biomedical subjects

Y Akagi

Publications and source records attributed to Y Akagi.

At least 109 records · Page 6Linked to original sources

[The localization and production of interleukin-1 in pharyngeal epithelium].

Interleukin-1 (IL-1) has been thought to be one of the essential cytokines mainly produced by macrophage. The function of IL-1 are not only activates T-lymphocytes, but also regulates immune responses to several antigens and effects on local and systemic immune reactions. Recently, it is reported that epidermal keratinocytes produces IL-1, and attention has been paid to local immune reaction mediated with this cytokine. In this study, we performed immunohistochemistry and immunoblotting on the pharyngeal epithelial keratinocytes and we evaluated the production of IL-1 by these cells. Pharyngeal mucous membrane of each region reacted strongly against anti-IL-1 alpha antibody, on the contrary, anti-IL-1 beta antibody comparatively only weakly. Strong reactivity was often observed on the basal layer, then it was seemed that some important relationship exists between the production of IL-1 and maturation of pharyngeal keratinocytes. Infiltration of T-lymphocytes was observed in proportion to the increase of epithelial reactivity against IL-1. There seemed to be no correlation between expression of HLA-DR antigen on keratinocytes and reactivity of IL-1. In immunoblotting study, the 31kD band, intracellular immature molecule, was identified besides 17 and 52kD. From this finding, it was suggested that IL-1 is derived from pharyngeal keratinocytes. In conclusion, the present study is helpful for well-understanding of local cellular immunity of pharyngeal mucous membrane.

Adult↗

[Changes in cell kinetics of rat lens epithelial cells with aging].

Whole-mount preparations of developing rat lens epithelium were made and 3H-thymidine autoradiography was performed on them. The distribution of 3H-thymidine-labeled (DNA-synthesizing) epithelial cells was examined by the above combined methods. Labeled cells were evenly distributed in the epithelial cell layer (not the definitely germinal zone) until 1 week after birth. In 3- or 7-week-old rat lens, labeled cells were mainly distributed in the germinal zone, and the number of labeled cells localized in the anterior subcapsular epithelial cell layer decreased according to age of the rat. The 24-week-old rat showed localization of labeled cells at the germinal zone, which seemed to be similar to the human adult lens.

Aging↗

[The influence of aging on the development of rat galactosemic cataract].

In order to investigate the effect of age on the rat galactosemic cataract, 3, 6, 12 and 24-week-old rats were fed with a 50% galactose diet. The cataractous lenses were observed by light microscopy, and the amount of galactitol measured. All rats fed with 50% galactose developed cataracts in the equatorial region. However, the morphological and biochemical development of the galactose cataract in old rats was slower than in young rats. These results suggested that older diabetic patients are less likely to develop diabetic cataract than younger patients.

Aging↗

[Quantitative study of rat diabetic cataract, by the relaxation times of nuclear magnetic resonance].

The prophylactic effects of a new aldose reductase inhibitor (ARI), FR74366 on streptozotocin-induced rat diabetic cataract were examined by means of proton nuclear magnetic resonance (1H-NMR) relaxation time. We compared the findings with the histological finding, and it was recognized that longitudinal and transverse relaxation times (T1, T2) were prolonged before the histological changes appeared. The ARI, FR74366, prevented histologic changes and had detected by the 1H-NMR method. The results showed that 1H-NMR could be useful in the early detection of human diabetic cataract and the evaluation of the effectiveness of anti-cataract agents, for example, AR inhibitors.

Aldehyde Reductase↗

Possible induction of [Met]enkephalin-Arg6-Gly7-Leu8 immunoreactivity in neurons of the rat superior colliculus following eye enucleation.

The distribution of [Met]enkephalin-Arg6-Gly7-Leu8 (MEAGL)-immunoreactive (-IR) neurons and its modification after enucleation have been investigated in the rat superior colliculus. In normal rats and on the ipsilateral side of monocular-enucleated rats, small sized vertically elongated fusiform-shaped weakly immunostained neurons were dispersed throughout the sublamina of the stratum griseum superficiale (SGS). In bilaterally enucleated rats and on the contralateral side of monocular-enucleated rats, many small strongly immunoreactive MEAGL-containing neurons, projecting processes horizontally or obliquely toward the surface, appeared in the deepest part of the SGS and the superficial part of the stratum opticum (SO), in contrast to the disappearance of the fusiform-shaped weakly stained neurons in the SGS. MEAGL-IR fibers increased in density throughout the sublamina of the SGS, being densest in the deep SGS, accompanying their increase in the neighboring SO. Sporadically found MEAGL-IR neurons in the deep SO and the stratum griseum intermediale did not show the detectable change of immunoreactivity. These results indicate that enkephalin biosynthesis is undergone by different type of neurons in the normal and the ocular-derived superior colliculus, and suggest that some neurons in the adult superior colliculus have a potentiality to express the peptidergic phenotype.

Animals↗

Contrary effect of eye enucleation on VIP-immunoreactive neurons in the suprachiasmatic nucleus and the superior colliculus of the rat.

The topographic alternation of vasoactive intestinal peptide (VIP) immunoreactivity after long-term bilateral eye enucleation (80 days) was investigated in the suprachiasmatic nucleus (SCN) and the superior colliculus of the adult rat with the peroxidase-antiperoxidase method. In the SCN, the immunostaining of VIP-immunoreactive (IR) cell bodies increased, and the intensity and density of VIP-IR fibers and terminals were markedly enhanced after eye enucleation. On the other hand, after eye enucleation, no VIP-IR cell bodies and fibers were visible in the stratum griseum superficiale of the superior colliculus, although fusiform-shaped VIP-IR neurons were distributed in the layer of unoperated control rats. The present results, therefore, have revealed that the long-term blockage of retinal input induces changes of VIP immunoreactivity in different manners, according to the target brain areas.

Animals↗

Prevention of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by aldose reductase inhibitors.

Vascular changes associated with early diabetic retinopathy that include the selective degeneration of pericytes, the formation of microaneurysms and acellular capillaries, and vessel dilation have been experimentally investigated in age- and sex-matched beagle dogs fed a 30% galactose diet and treated with or without the aldose reductase inhibitors sorbinil and/or M79175. Eyes from dogs in each group were periodically enucleated during a 36-month period and their retinal capillaries were examined as trypsin-digested flat preparations. These studies reveal that the destruction of retinal pericytes to form pericyte ghosts is the earliest observable retinal vessel change occurring after 19 to 21 months of galactose feeding. By 24 months, both an irregular distribution of endothelial cell nuclei near pericyte ghosts and the presence of acellular capillaries containing neither endothelial cells nor pericytes can be observed. This was followed by the histologic appearance of microaneurysms after 27 months and the funduscopic appearance of intraretinal hemorrhages after 33 months. Varicose enlargements of capillaries were also observed in the trypsin-digested preparations from dogs fed galactose for 33 to 36 months. All of these changes are linked to the initial aldose reductase-associated destruction of pericytes. The onset and progression of these retinal changes were retarded in a dose-dependent manner with aldose reductase inhibitors.

Aldehyde Reductase↗

Effect of aldose reductase inhibitors on the progression of retinopathy in galactose-fed dogs.

The onset and progression of diabetic-like retinopathy has been investigated in age-matched male beagle dogs fed a 30% galactose diet. Examination of the intact retinal vessels, isolated by gentle trypsin digestion, reveals that the destruction of pericytes to form pericyte ghosts is the earliest observable retinal vessel change. This results in an irregular distribution of endothelial cell nuclei near pericyte ghosts and the subsequent formation of acellular capillaries containing neither endothelial cells or pericytes. This was followed by the histological appearance of microaneurysms and later, by the funduscopic appearance of intraretinal hemorrhages. Studies in similar galactose-fed dogs treated with aldose reductase inhibitors indicate that all of these changes are linked to the initial aldose reductase associated destruction of pericytes.

Aldehyde Reductase↗

[Preventional and therapeutic effects of aldose reductase inhibitor FR74366 on rat galactose cataract].

Preventional and reversal effects of a new aldose reductase inhibitor FR74366 on the rat galactose cataract were examined biochemically and light microscopically. A high concentration (0.075%) FR74366 showed sufficient effects both to prevent and reverse cataract, but low concentrations (0.025%) FR74366 was not effective as 0.075% FR74366. These results indicate that FR74366 can be useful drug for cataract.

Aldehyde Reductase↗

Two sisters with impetigo herpetiformis.

Two sisters (non-twins) had impetigo herpetiformis triggered by their first pregnancy. One sister treated with etretinate had good resolution of skin disease. Impetigo herpetiformis is probably a variant of pustular psoriasis and may be provoked or precipitated by factors, such as pregnancy. Both patients shared common HLA antigens (All, AW24, BW44, BW54 and DR6Y).

Adult↗

An autopsy case of breast carcinoma with prominent lipid-secretions in the metastatic foci.

A 70-year-old woman was treated with a simple mastectomy followed by a course of 5000 rad to the breast and chemotherapy with 5-fluorouracil for breast cancer. About 15 months later, the patient died of widespread metastases. An autopsy revealed no recurrent cancer in the breast. The metastases were seen in bones (sternum, ribs and spine), pleura, spleen, uterus, ovaries, small intestine, adrenal glands, and lymph nodes (hilar, periaortic and mesenteric). Histologically, the resected tumor was a solid-tubular carcinoma with an infiltrative growth pattern. At autopsy, the tumor cells in the metastatic foci contained an abundance of lipids in the cytoplasm, while the tumor cells in the primary tumor contained small amounts of lipids.

Adenocarcinoma↗

The effect of aldose reductase inhibitor, statil, on hyperpermeability of iridial vessels in experimental galactosemic rats.

Thirty young male Sprague-Dawley rats were divided into three groups: the control group, given a normal diet; the galactose group, given a 25% galactose diet; and the aldose reductase-galactose group, given a 25% galactose diet containing 0.046% Statil, an aldose reductase inhibitor. The results suggested that Statil could prevent hyperpermeability of iridial vessels in galactose-fed rats.

Aldehyde Reductase↗

[Morphological classification of the prevention by aldose reductase inhibitor of rat galactosemic cataract].

A morphological classification indicating the stage of the prevention of aldose reductase inhibitor (ARI) on the rat galactosemic cataract was investigated. Three week old rats (body weight 50 g) were fed with a 25% galactose diet. Two kinds of ARIs (ADN-138, FR-74366) were used with a different dose 25% galactose fed each drug. The rats on the 25% galactose diet rapidly developed cataracts in the equatorial region of the lens followed by total cataracts. The morphological processes of the galactose cataracts receiving preventive treatment of ARI were divided into 5 types according to their intensity.

Aldehyde Reductase↗

[Movement of regenerated lens epithelial cells in 50% galactose cataract and an aldose reductase inhibitor].

In experimental galactose cataract of rats, lens fiber cells were gradually destroyed by swelling and liquefaction occurring due to the accumulation of galactitol. In addition to the destruction of lens fiber cells, marked regeneration of lens epithelial cells was universally observed. In this study, we used the technique of 3H-thymidine autoradiography and examined the movement of regenerated (DNA synthesis) lens epithelial cells. On the fourth day from the starting of 50% galactose chow, 3H-thymidine was injected into the anterior chamber. After one week, 3H-thymidine-labelled epithelial cells was observed at the bow region of the equatorial area. After 2 to 4 weeks, labelled cells were found in the regenerated lens fibers of the cortex. After 3 weeks, labelled cells about to be destroyed by swelling and liquefaction were recognized. However, a few labelled cells were still observed in the epithelial cell layer. The same experiments were performed in two groups of normal chow-fed one and 50% galactose + an aldose reductase inhibitor (Statil)-fed one. The movements of 3H-thymidine labelled epithelial cells in the above two groups were almost identical. In addition, the movement of labelled cells was normalized by an aldose reductase inhibitor.

Aldehyde Reductase↗

[Ciliary body changes associate with aldose reductase in galactosemic rats].

Morphological changes of the ciliary body epithelium in rats fed a 50% galactose diet for 10 months with or without aldose reductase inhibitor (ARI) were investigated by both light microscopic observation and measurement of cell size. Aldose reductase was immunohistochemically observed to be present in non-pigmented epithelial cells of ciliary body and structural change (hypertrophy) was observed only in non-pigmented epithelial cells of galactosemic rats. In contrast, no hypertrophic changes were seen in rats fed with ARI. These results strongly suggest that aldose reductase is associated with hypertrophic change of non-pigmented epithelial cells of the ciliary body.

Aldehyde Reductase↗

Prevention of pericyte ghost formation in retinal capillaries of galactose-fed dogs by aldose reductase inhibitors.

A distinguishing feature of early diabetic retinal vascular changes is the selective degeneration of pericytes (mural cells) from the retinal capillary vessels. Loss of these pericytes has been proposed to be associated with decreased capillary tonicity, the formation of microaneurysms, and vessel dilation. The role of aldose reductase in the progression of diabetic retinopathy has been investigated in age- and sex-matched beagles fed a 30% galactose diet with or without the aldose reductase inhibitors sorbinil or M79175. Eyes were periodically enucleated from dogs in each group and their retinal capillaries were examined as trypsin-digested flat preparations. Before the clinical appearance of retinal changes, pericyte ghost formation was observed in the eyes of three fourths of the dogs after 21 months and all of the dogs after 24 months of galactose feeding. Many of the capillaries containing pericyte ghosts demonstrated an apparent proliferation of endothelial cells and acellular vessels. No pericyte ghosts or abnormal findings were observed in retinas from either normal control (zero of nine) or galactose-fed dogs treated with aldose reductase inhibitors (zero of 16). These findings indicate that aldose reductase inhibitors can prevent the formation of pericyte ghosts and other subsequent capillary changes in experimental retinopathy.

Animals↗