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Biomedical subjects

S Hidaka

Publications and source records attributed to S Hidaka.

At least 73 records · Page 4Linked to original sources

Thermal analysis of bones from ovariectomized rats.

Thermal analyses [thermogravimetry (TG) and differential thermal analysis (DTA)], X-ray diffraction, and infrared absorption analysis of bones from ovariectomized rats were carried out. The rats were divided into five groups: sham operated (Sham); ovariectomized (OVX); OVX given traditional Chinese (Kampo) medicine, Unkei-to; OVX given 17 beta-estradiol; and OVX given the estradiol vehicle, respectively. The activation energy (delta E), a kinetic parameter from TG data of OVX rats, increased by 57% from that in Sham rats. The administration of Unkei-to and 17 beta-estradiol to OVX rats clearly restored the delta E to the levels of Sham rats, while the vehicle for 17 beta-estradiol had no effect. DTA data from thermal analyses of rats from the Sham, OVX, and OVX given various compounds were almost the same except for OVX rats given 17 beta-estradiol. The X-ray diffraction pattern and infrared absorption spectrum of bone powders from Sham rats were not different from those of OVX rats or others. These results strongly suggest that kinetic parameter, delta E calculated from TG data, may be a useful method for assessing both experimentally induced osteoporosis and drug effects on it.

Animals↗

Voltage-gated Na+ current availability after step- and spike-shaped conditioning depolarizations of retinal ganglion cells.

We used two conditioning voltage protocols to assess inactivation of voltage-gated Na+ current in retinal ganglion cells. The first protocol tested the possibility, raised by published activation and steady-state inactivation curves, that Na+ ions carry a "window" current in these cells. The second protocol was used, because these cells spike repetitively in situ, to measure the Na+ current available for activation following spikes. Na+ current activated at test potentials more positive than –65 mV. At test potentials more positive than –55 mV, Na+ current peaked and then declined along a time course that could be fit by the sum of a large, rapidly decaying component, a small, slowly decaying component and a non-decaying component. Both step- and spike-shaped conditioning depolarizations reduced the amount of current available for subsequent activation, sparing the non-decaying "persistent" component. Most of the Na+ current recovered from this inactivation along a rapid exponential time course (τ=3 ms). The remaining recovery was complete within at least 4 s (at –70 mV). Our use of step depolarizations has identified a current component not anticipated from previous measurements of steady-state inactivation in retinal ganglion cells. Our use of spike-shaped depolarizations shows that Na+ current density at 1 ms after a single spike is roughly 25% of that activated by the conditioning spike, and that recovery from inactivation is 50–90% complete within 10 ms thereafter. Na+ current amplitude declines during spikes repeated at relatively low frequencies, consistent with a slow component of full recovery from inactivation.

Action Potentials↗

IL-2-induced growth of CD8+ T cell prolymphocytic leukemia cells mediated by NF-kappaB induction and IL-2 receptor alpha expression.

The binding of interleukin-2 (IL-2) to its receptor on normal T cells induces nuclear expression of nuclear factor kappaB (NF-kappaB), activation of the IL-2 receptor (IL-2R) alpha chain gene, and cell proliferation. In the present study, the role of IL-2R signaling in the growth of CD8+ T cell prolymphocytic leukemia (T-PLL) cells has been investigated. Flow cytometry revealed that primary leukemia cells from a patient with CD8+ T-PLL expressed IL-2Ralpha and beta chains, and the cells showed a proliferative response and an increase in IL-2Ralpha expression on culture with exogeneous IL-2. Northern blot analysis failed to detect IL-2 mRNA, suggesting that IL-2 may act in a paracrine manner in vivo. Electrophoretic mobility-shift assays revealed that recombinant IL-2 increased NF-kappaB binding activity in nuclear extracts of the leukemia cells, and Northern blot analysis showed that IL-2 increased the abundance of mRNAs encoding the NF-kappaB components c-Rel and KBF1 in these cells. IL-2 binding analysis demonstrated that IL-2 markedly increased the number of low affinity IL-2Rs on the leukemia cells, without an effect on the number of high-affinity IL-2Rs. These results show that IL-2 is capable of inducing the nuclear expression of NF-kappaB in primary CD8+ T-PLL cells, and that this effect is mediated, at least in part, at a pretranslational level.

Blotting, Northern↗

Altered anionic GBM components in monoclonal antibody against slit diaphragm-injected proteinuric rats.

BACKGROUND: We previously reported that monoclonal antibody (mAb) 5-1-6 bound to renal filtration slits induces massive proteinuria without causing ultrastructural changes in the glomerulus. This study evaluated the underlying mechanisms of the increase in glomerular permeability. METHODS: The distribution of endogenous albumin and IgG in the glomerular basement membrane (GBM) was studied in in situ drip-fixed glomeruli of Munich-Wistar rats by use of immunogold immunocytochemistry in the presence and absence of mAb 5-1-6. The density of foot process glycocalyx components was estimated by labeling with Limax fluvus lectin- or Helix pomatia lectin-gold complexes. Anionic sites in the GBM were examined by labeling with cationic gold at pH 2.0 or 7.4. Carboxyl groups, which also furnish an anionic charge to the GBM, were examined by specific biotinylation and colloidal gold probe methods. In addition, the infusion-staining of anionic sites was performed by use of ruthenium red in both Munich-Wistar and Wistar rats. RESULTS: The urinary excretion of albumin and IgG was increased markedly in the treated rats, indicating a non-selective barrier defect. In the control rats, albumin and IgG molecules were mainly located along the inner half of the GBM, and to a lesser degree in the lamina rara externa. In the treated rats, the albumin and IgG moieties were more equally distributed throughout the width of the GBM. Newly appearing, small dense peaks at the outer side of the GBM were evident, indicating a barrier function of outer zone of the GBM and/or epithelial cell layer. No intergroup differences in the density of lectin binding sites on foot processes were seen. The reduction in the number of ruthenium red-positive anionic sites and cationic gold (pH 2. 0)-labeled anionic sites in the lamina rara externa was significant in the treated rats at day 3, indicating a possible alteration of charged proteoglycan in the lamina rara externa. No such changes were seen with cationic gold (pH 7.4)-labeled anionic sites in the GBM. The density of labeled carboxyl groups was significantly reduced in the treated rats relative to the controls. CONCLUSIONS: These results show that the injection of mAb 5-1-6 induced a perturbation of the charge- and probably the size-selective glomerular filtration barrier. The observed reduction in the levels of various negatively charged substances resulted in massive proteinuria, implying that alteration of target antigens can affect the integrity of the GBM constituents maintaining the normal barrier function.

Albuminuria↗

Effect of cholinergic blockade on inhibited GH secretion by feeding and intraruminal SCFA infusion in sheep.

The effect of cholinergic blockade on suppressed growth hormone (GH) secretion caused by feeding or the intraruminal infusion of an acetate, propionate, and butyrate mixture (107 and 214 mumol.kg-1.min-1 over 6 h) was examined in ovariectomized ewes. Intraruminal infusion at the rate of 107 mumol.kg-1.min-1 increased peripheral plasma short-chain fatty acid (SCFA) concentrations to approximately the physiological levels noted after feeding. Plasma GH was markedly suppressed by feeding and at both the 107 and 214 mumol.kg-1.min-1 SCFA infusion rates; however, cholinergic blocking agents completely blocked the suppressed GH secretion after feeding and only at the 107 mumol.kg-1.min-1 infusion rate. Plasma glucose increased at both infusion rates, and the plasma free fatty acids decreased after feeding and at both infusion rates. However, both metabolites were unchanged relative to the saline control after the injection of the cholinergic antagonists. It is suggested that the decrease in plasma GH observed after feeding and a near-physiological ruminal SCFA increment is mediated via the parasympathetic nerve and not by pharmacological ruminal SCFA increments attributed to other pathways.

Animals↗

Morphology and morphometry of skulls of raccoon dogs, Nyctereutes procyonoides and badgers, Meles meles.

In order to obtain the basic data to identify the skeletal remains from the archaeological sites, morphological and morphometrical studies were carried out on skulls of living raccoon dogs (35 males and 45 females) and badgers (16 males and 8 females) from Kagoshima Prefecture. Macroscopically, the sexual differences were observed in badgers for the parts of the zygomatic process of the temporal bone and the occipital squama, but were not in raccoon dogs. Among 24 cranial measurements, significant sexual differences were found in five measurement items in raccoon dogs, while 12 items in badgers. Mandibles showed significant sexual differences in both species. Raccoon dogs had significantly larger values than badgers in most of the items concerning length of cranium and most mandibular measurements. The discrimination efficiencies of discriminant formulae between both sexes were lower in raccoon dogs, but higher in badgers, and the efficiencies between both species were obtained 100%. In the regression formulae for estimating skull length, some formulae showed high coefficients of determination in both species. These observations represented interspecific and sexual differences in the skulls of raccoon dogs and badgers.

Animals↗

A histometrical study on the long bones of raccoon dogs, Nyctereutes procyonoides and badgers, Meles meles.

To obtain the data required for identification of skeletal remains excavated from archaeological sites, histometrical observations were made in the cross sections of the mid-shaft of humerus, radius, femur and tibia of raccoon dogs (Nyctereutes procyonoides) and badgers (Meles meles) captured in Kagoshima Prefecture. There were interspecific differences between both animals in the breadth, the depth and the area of medullary cavity at the mid-shaft of the bones, all measurements were greater in male than in female bones. The thickness and the area of compact bones in male raccoon dogs were larger than those of female. No differences in histological structure could be detected among the bones, but an interspecific difference was found in the shape of osteons; round and constant-sized osteons consisting of 3 to 5 lamellae in raccoon dogs, while round or elliptic osteons varying in size from 3 to 8 lamellae in badgers. The ratios, the osteon areas per unit compact bone areas, were higher in all the bones of raccoon dogs. The short diameters of osteons and the ratios were greater in males in both animals. In females, the short diameter of osteons was smaller, and the number of osteons was larger. The results revealed interspecific differences between both animals and sexual dimorphism in each species.

Animals↗

Histological changes in mouse nipple tissue during the reproductive cycle.

To obtain detailed information about the histological changes occurring in the mouse nipple during the reproductive cycle, we examined and quantified the S-phase of cell by immunohistochemical staining with bromodeoxyuridine (BrdU), and analysed histologically the subepithelial fibrous elements. The nipple markedly increased in size dramatically on days 15-18 of pregnancy. The densities of cells in the epidermis and dermis were very high during the early stages of pregnancy but low during lactation. In the epithelium of the lactiferous sinus, the densities of cells did not differ significantly among stages. The BrdU antibody labeling revealed a number of BrdU-positive cells in the basal layer of the epidermis and epithelium of the lactiferous sinus. The ratios of BrdU-positive cells to total cells in the epidermis and the epithelium of the lactiferous sinus were highest on day 15 and day 10 of pregnancy, respectively. After lactation, however, the ratios were similar to those in the virgin stage. No significant differences were detected in the dermis among all stages. The number of collagen and elastic fibers increased during lactation. These results indicate that cells in the epidermis and lactiferous sinus proliferated actively from day 10 to day 15 of pregnancy. The observation that cellular proliferation in the epithelial system of the nipple was stimulated at the early stage of pregnancy, while the dermis has two growth phases, with cellular proliferation during pregnancy and an increase in extracellular matrix during lactation, suggests that these two phenomena might be regulated by different factors.

Animals↗

Histological and morphometrical studies on the rat nipple during the reproductive cycle.

Histological changes in the rat nipple during the reproductive cycle were observed. In virgin and the first half (days 5 and 10) of pregnancy, the nipple had a dull conical shape and the germinative layer of epidermis, thicker than that of the skin surrounding the nipple, deeply ingrew into the dermis in the basal region. From the second half (days 15 and 20) of pregnancy to the post-weaning period, the nipple appeared columnar in shape and many wrinkles were observed in the nipple wall especially during the lactating period. Collagen fibers longitudinally running in the nipple wall mainly comprised the dermis of the nipple and became loose during lactation. Small numbers of elastic fibers running parallel with smooth muscles were also observed in the nipple wall, and these increased in number and thickness from the second half of pregnancy, and most became frizzy structures during lactation. Around the lactiferous sinus, smooth muscle cells were arranged longitudinally but a few muscle cells were seen in a concentric layer, but during the lactating period the sinus was distended and many epithelial folds were observed. Morphometrical analysis indicated that the length of the nipple increased from the second half of pregnancy and reached the maximum on day 15 of lactation, approximately 3.7 times that in the virgin period. The outer diameter of the nipple and thickness of the nipple wall during lactation also reached approximately twice that in virgin. The size of the nipple decreased gradually after weaning. These observations suggest that the histological changes in the rat nipple during the reproductive cycle were mainly characterized by hyperplasia of the epidermis and hypertrophy of connective tissue in the dermis from the second half of pregnancy.

Animals↗

Micacocidin A, B and C, novel antimycoplasma agents from Pseudomonas sp. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

A Gram-negative bacterium was found to produce a new zinc-containing antibiotics, micacocidin A and related compounds containing Cu or Fe, micacocidin B and C, respectively. These antibiotics were isolated by column chromatography on silica gel, and then separated by preparative TLC and HPLC. These new antibiotics exhibited an excellent activity against Mycoplasma species. The producing bacterium was characterized and ascribed to the genus Pseudomonas.

Anti-Bacterial Agents↗

[Membranoproliferative glomerulonephritis-like lesion with fibrillary deposition associated with multicentric Castleman's disease].

We report a case of a 65-year-old man presenting with multicentric Castleman's disease (MCD) accompanied by membranoproliferative glomerulonephritis-like lesion with fibrillary deposits. The lesion was characterized by highly organized ultrastructual deposits that were negative for Congo-red stain and for immunoglobulin, light chain and C3. Thus, this renal lesion was considered histologically to be fibrillary glomerulonephritis presenting by light microscopy as mesangiocapillary glomerulonephritis. To our knowledge, among the limited number of cases of renal lesion associated with MCD ever reported, this is the first case of a biopsy-proven fibrillary glomerulonephritis. Serum interleukin 6 (IL-6), known as an indicator of MCD activity and as an autocrine growth factor for mesangial cells, was chronologically measured. Augmentation of urinary IL-6 simultaneously with that of extra renal symptoms of MCD and associated renal disease may indicate an underlying role of this cytokine in the present case. Failure to detect of IL-6 in the glomeruli may support the notion that IL-6 is derived from extrarenal lymphonodi, and not to an in situ product of the glomeruli. However, it may have been related to glomerular injury.

Aged↗

Enhanced expression of uncoupling protein 2 gene in rat white adipose tissue and skeletal muscle following chronic treatment with thyroid hormone.

Evidence is rapidly emerging which suggests that uncoupling protein 2 (UCP2), by virtue of its ubiquitous expression, may be important for determining basal metabolic rate. To assess the functional modulation of UCP2 gene expression in relation to body weight control, we examined the effects of hyperthyroid state induced by chronic treatment with triiodothyronine (T3) on UCP2 mRNA expression in male rats. Daily subcutaneous injection of T3 (37 pmol/100 g body weight) for 7 days increased UCP2 mRNA expression in brown adipose tissue (BAT), white adipose tissue (WAT) and the soleus muscle 1.6-, 1.6- and 1.7-fold compared to the controls, respectively, and increased UCP1 mRNA expression in BAT 1.2-fold. In contrast, the same treatment with T3 decreased both ob mRNA expression in WAT and plasma leptin level 0.5-fold for each. The present results suggest that T3 may directly increase UCP2 expression independently of leptin action.

Adipose Tissue↗

Correlation between vitamin D receptor genotypes and bone mineral density in Japanese patients with osteoporosis.

In order to better understand the pathogenesis of osteoporosis, we investigated the correlation between the vitamin D receptor (VDR) genotypes defined by BsmI restriction enzyme, as well as other related factors, and the bone mineral density (BMD) at the lumbar spine in 90 Japanese patients with osteoporosis. The same study was performed in 36 patients with osteoarthrosis of the hip joint and 92 healthy volunteers. The majority of the VDR genotypes were bb, and a few of the population showed either the BB or Bb genotype in all three groups. There was no statistical difference in the frequencies of these VDR genotypes in the three groups. The mean age-matched value of BMD (Z scores) at the lumbar spine in patients with osteoporosis was significantly lower than that in patients with osteoarthrosis or healthy volunteers. The mean Z scores of the healthy volunteers with bb genotype were significantly higher than those with BB genotype, whereas those of the osteoporosis patients with BB genotype were significantly higher than those with Bb genotype. There was no significant difference in the mean Z scores between bb and Bb genotypes in patients with osteoporosis and healthy volunteers. No significant difference was seen in the mean Z scores in patients with osteoarthrosis regardless of genotype. On the other hand, body weight significantly correlated with BMD in patients with osteoporosis by simple- and multiple-regression analysis. These results indicate that the BMD at the lumbar spine in Japanese patients with osteoporosis is affected by body weight, and might be affected partially by the VDR genotypes defined by BsmI.

Adult↗

Preventive effects of traditional Chinese (Kampo) medicines on experimental osteoporosis induced by ovariectomy in rats.

Preventive effects by traditional Chinese (Kampo) medicines, Unkei-to, Hachimi-jio-gan, and Juzen-taiho-to, on the progress of bone loss induced by ovariectomy in rats were investigated for a period of 49 days. The bone mineral density (BMD) of tibia in ovariectomized (OVX) rats decreased by 20% from those in sham-operated (Sham) rats, with the decrease completely inhibited by the administration of any one of these Kampo medicines or 17beta-estradiol. From scanning electron microscopic (SEM) analyses, the surface of a trabecular bone of tibia in OVX rats had a porous or erosive appearance, whereas that of the same bone in Sham rats was composed of fine particles. The administration of three Kampo medicines and 17beta-estradiol to OVX rats preserved the fine particle surface of the trabecular bone. These results strongly suggest that any of these three gynecological Kampo medicines is as effective as 17beta-estradiol in preventing the development of bone loss induced by ovariectomy in rats.

Absorptiometry, Photon↗

Frequent expression of interleukin-9 mRNA and infrequent involvement of interleukin-9 in proliferation of primary adult T-cell leukemia cells and HTLV-I infected T-cell lines.

To examine the possibility that interleukin-9 (IL-9) may be involved in oncogenesis and the proliferation of adult T-cell leukemia (ATL) cells, we examined the expression of IL-9 mRNA and growth response to IL-9 in five human T-lymphotropic virus type-I (HTLV-I) infected T-cell lines and in primary leukemia cells in peripheral blood from eight patients with ATL (four acute ATL and four chronic). Four out of five cell lines expressed IL-9 mRNA not correlated with Tax expression. Primary ATL cells from all patients also expressed IL-9 mRNA not correlated with the clinical forms. Recombinant IL-9 showed growth enhancing activity in only one out of five cell lines and one out of eight patients' primary leukemic cells. These results suggest the infrequent involvement of IL-9 in the proliferation of ATL cells, both primary tumor cells and HTLV-I infected T-cell lines.

Adult↗

Granulocyte-colony stimulating factor induces differentiation and apoptosis of CD2, CD7 positive hybrid leukemia cells in vivo and ex vivo.

We report a case of a 70-year-old man with a hybrid leukemia treated successfully with granulocyte-colony stimulating factor (G-CSF) combined with a cytocine arabinoside regimen through the induction of differentiation of leukemic cells into monocytoid cells resulting in apoptosis. The leukemic cells demonstrated a TCR-gamma rearrangement, and expressed CD2, CD7, CD33 and G-CSF receptors but not CD11b on the cell surface nor non-specific esterase in cytoplasm. Several days following the administration of G-CSF, the cells with monocytoid characteristics such as CD11b and cytoplasmic non-specific esterase appeared in the peripheral blood replacing the blastic cells. The cells were shown to be derived from the same clone of the leukemic cell because of the identical TCR-gamma gene rearrangement. The short-term culture of leukemic cells with G-CSF induced the differentiation into a monocyte lineage, resulting in apoptosis. Although there is no denying the possibility that cytosine arabinoside is partly responsible, our results strongly suggest that G-CSF plays the main role in differentiation of leukemic cells into a monocyte lineage inducing apoptosis in vivo in this patient.

Aged↗

Granulocyte-colony stimulating factor-induced proliferation of primary adult T-cell leukaemia cells.

Granulocyte-colony stimulating factor (G-CSF) is known to induce proliferation and differentiation of granulocyte progenitors, and is widely used to treat neutropenia induced by intensive chemotherapy for malignant lymphoma or adult T-cell leukaemia/lymphoma (ATL). G-CSF is thought not to stimulate malignant lymphoid cells. In the present study we examined the ability of G-CSF to induce in vitro growth of primary ATL cells from 14 patients (nine acute-type, two chronic-type and three lymphoma-type), and we analysed the in vivo counts of ATL cells in patients who received G-CSF for neutropenia. FACS analysis using phycoerythrin-labelled recombinant G-CSF demonstrated that ATL cells from 11/14 patients express some G-CSF receptor (G-CSFR), with a range between 5.4% and 87.3%. Cells expressing G-CSFR also expressed CD4. Reverse polymerase chain reaction (PCR) analysis demonstrated expression of G-CSFR messenger RNA in G-CSFR expressing cells. Leukaemic cells derived from seven (four acute-type, one chronic-type and two lymphoma-type) of the 14 patients proliferated in vitro in response to G-CSF, as measured by [3H]thymidine incorporation; maximum responses were at G-CSF concentrations of 10-100 ng/ml. Nine of 14 patients receiving rG-CSF for neutropenia were analysed retrospectively for ATL cell numbers. Four patients whose primary tumour cells proliferated in response to rG-CSF in vitro showed a significant increase in ATL cell count after administration of rG-CSF (P = 0.038), whereas five patients whose leukaemic cells did not proliferate in vitro showed no significant increase in ATL cell count. G-CSF can stimulate proliferation of ATL cells which may complicate therapy for this disease.

Aged↗

Cell type- and positionally specific regulation of the aldolase P gene expression in rice seedlings.

We describe here different regulation of the AldP gene, a nuclear gene encoding chloroplast aldolase, in different tissues and growth ages of rice seedlings. Expression of the AldP gene is mesophyll cell-specific, and increases from the basal to the upper region in each leaf. The gene expression is repressed in the dark-grown leaf blade, but is induced by a short-term-exposure to light, to a level higher than that seen in the normal leaf blade. However, the light-inducibility differs among the tissues, and shows different patterns among leaf positions; i.e., the extent of light-induction is higher in the third leaf blade as compared with the earlier developed second leaf blade. Such positional differences in the regulation are also seen in the leaf sheath. These responses are not accompanied by changes of the cell type specificity in the expression.

Fructose-Bisphosphate Aldolase↗