PubMed Health⌕ Search

Biomedical subjects

S Hisano

Publications and source records attributed to S Hisano.

At least 37 records · Page 2Linked to original sources
PubMed1999

Vitamin E suppresses oxidative stress and glomerulosclerosis in rat remnant kidney.

Previous studies have shown that reduction of renal mass in the rat remnant kidney model induces overproduction of transforming growth factor beta1 (TGFbeta1). We investigated whether an antioxidant, vitamin E, administered before the renal mass reduction, could prevent oxidative stress, reduce the overproduction of TGFbeta1, and mitigate against the subsequent glomerulosclerosis. Our results revealed that the oxidative stress, as measured by the change in plasma malondialdehyde, is significantly reduced by prior vitamin E dietary supplementation. Finally, our data show that dietary vitamin E supplementation ameliorates the rise in TGFbeta1 secondary to renal mass reduction and inhibits the glomerular sclerosis of the remnant kidney over the time course of this experiment.

Animals↗
PubMed1999

Jumping translocation of homogeneously staining region and tetraploidy with double minutes in acute myelomonocytic leukemia.

We report a 71-year-old patient with acute myelomonocytic leukemia (AMMoL) who had complicated chromosomal abnormalities showing diploidy with a jumping translocation of a homogeneously staining region (hsr) and tetraploidy with double minutes (dmin). The analysis of gene amplification showed that hsr and dmin were the results of C-ETS 1 gene amplification. After induction chemotherapy, tetraploidy with dmin completely disappeared, while diploidy with hsr and del(11)(q23) remained until the patient died. It is speculated that hsr is more stable than dmin during chemotherapy and that the presence of tetraploidy is not necessarily a factor of poor response to chemotherapy for acute leukemia.

Aged↗
PubMed1999

Regulation of growth hormone-releasing hormone receptor messenger ribonucleic acid expression by glucocorticoids in MtT-S cells and in the pituitary gland of fetal rats.

Regulation of GH-releasing hormone receptor (GHRH-R) messenger RNA (mRNA) expression was studied, with the ribonuclease protection assay, in the fetal rat pituitary gland and in MtT-S clonal cells. GHRH-R mRNA was first detected on embryonic day (E)19 and increased rapidly thereafter, to reach a maximum at E21. Incubation of E17 or E18 pituitaries with 50 nM dexamethasone (DEX), a synthetic glucocorticoid, induced GHRH-R mRNA expression, suggesting that glucocorticoids play a pivotal role in the developmental expression of this mRNA. In E19 pituitaries, 24 h treatment with DEX increased GHRH-R mRNA by 60%, and GH mRNA by 76%, but did not affect pit-1 mRNA level, suggesting that the effect of DEX is specific for expressions of GH mRNA and GHRH-R mRNA. The accumulation of GHRH-R mRNA by DEX was time dependent, and it was slightly enhanced by the protein synthesis inhibitor, puromycin (100 microM). In MtT-S cells (a pituitary cell line established from an estrogen-induced tumor), DEX induced GHRH-R mRNA expression within 2 h in a dose-dependent manner. This induction was augmented by puromycin (100 microM) or cycloheximide (3.5 microM). However, the RNA synthesis inhibitor Actinomycin D (1 microM) completely inhibited GHRH-R mRNA accumulation in response to either DEX or DEX plus puromycin, suggesting that glucocorticoids induce GHRH-R mRNA mainly through stimulation of mRNA transcription. These results suggest: that GHRH-R mRNA accumulation in the fetal pituitary gland of rats normally occurs at E19, probably because of the direct action of glucocorticoids on the pituitary gland, to stimulate GHRH-R mRNA transcription; and that the expression of glucocorticoid receptors is an important event in GH cell development in rats. Accordingly, immunocytochemical results suggest an increase in glucocorticoid receptors in immature GH cells between E17 and E18. The present results also imply that MtT-S cells may be a good model in which to further study the molecular mechanisms of the regulation of GHRH-R gene expression.

Animals↗
PubMed1999

Effect of the synthetic glucocorticoid, deflazacort, on body growth, pulsatile secretion of GH and thymolysis in the rat.

DESIGN: Deflazacort (DFZ) is a relatively new glucocorticoid that has been reported to exhibit fewer side-effects than other commonly used corticosteroids. The present study was designed to test the effects of DFZ on thymus gland involution (thymolysis), as compared with body growth and the secretory pattern of GH in the rat. Beginning at 38 days of age, male animals were treated for 8 consecutive days by s.c. injection of DFZ (0.15mg/day), cortisone (CORT) (5mg/day) or vehicle (control, CTRL). RESULTS: Both glucocorticoids had a similar thymolytic effect and caused growth failure, but the growth rate for the DFZ group was significantly higher than that of the CORT group. On day 46, pulsatile GH secretion was quantitated by blood sampling via an indwelling catheter at 10 min intervals for 6h. GH was assayed by RIA and analyzed by multiparameter deconvolution. CORT caused an increase in pulse frequency (5.8+/-0.4 (s.e.m.)) in comparison to DFZ (4.4+/-0. 4) and CTRL (3.8+/-0.3). Both glucocorticoids significantly shortened the interval between secretory bursts. In CTRL animals the interval between bursts was 69.3+/-4.5 min. In DFZ animals this was reduced to 58.5+/-7.1 min, and in CORT rats it was further reduced to 47.0+/-2.6 min. The mass of GH secreted per burst was reduced in CORT animals (52% of CTRL), while DFZ did not alter this parameter. A similar trend was observed for total GH production, with CORT causing a reduction and DFZ not affecting the secretion. CONCLUSION: Rats treated with glucocorticoid show a profound thymolytic effect, as well as important changes in growth. While CORT suppresses GH secretion and alters its pulsatile mode of release, DFZ causes a less significant alteration in the pattern of GH secretion and does not negatively affect the overall amount of GH secreted.

Animals↗
PubMed1999

[An early phase II study of autologous peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission. Japan Blood Cell Transplantation Study Group].

We performed a multicenter, an early phase II clinical trial to evaluate the feasibility, safety and efficacy of myeloablative therapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of acute myelogenous leukemia (AML) in first remission. A total of 105 patients were enrolled in the study, and 56 patients in first complete remission received auto-PBSCT. The median age was 44 years. Of the 56 patients, 34 (60.7%) had M2 or M3 AML by the French-American-British Classification system. The median concentration of infused CD34+ cells was 2.3 x 10(6)/kg by recipient body weight. Median days to reach an absolute neutrophil count > 500/microliter and a platelet count > 20000/microliter were 14 and 16, respectively. The median disease-free survival rate was estimated to be 62.0% at a median follow-up time of 534 days. Although the study enrolled a small number of patients and the follow-up period was relatively short, the preliminary results were encouraging and indicated that myeloablative chemotherapy with auto-PBSCT is feasible and can be performed safely as a post-remission therapy for AML. A prospective randomized clinical trial of auto-PBSCT versus standard chemotherapy alone will be necessary to assess the efficacy of high-dose therapy facilitated by auto-PBSCT as a post-remission therapy for AML.

Adolescent↗
PubMed1998

Effects of dietary Pi on the renal Na+-dependent Pi transporter NaPi-2 in thyroparathyroidectomized rats.

Dietary Pi and parathyroid hormone (PTH) are two most important physiological and pathophysiological regulators of Pi re-absorption in the renal proximal tubule. Effects of dietary Pi on Na+/Pi co-transporter NaPi-2 were investigated in thyroparathyroidectomized (TPTX) rats. NaPi-2 protein and mRNA in the kidney cortex of TPTX rats were increased approximately 3.8- and 2.4-fold in amount respectively compared with those in the sham-operated animals. Administration of PTH to the TPTX rats resulted in a decrease in the amount of NaPi-2 protein, but not in the abundance of NaPi-2 mRNA. Deprivation of dietary Pi in the TPTX rats did not affect the amount of NaPi-2 mRNA and protein. In the Pi-deprived TPTX rats, feeding of a high-Pi diet resulted in marked decreases in Pi transport activity and the amount of NaPi-2 protein in the superficial nephrons. Immunohistochemical analysis demonstrated that administration of PTH to TPTX rats resulted in a decrease in NaPi-2 immunoreactivity from both superficial and juxtamedullary nephrons within 4 h. Switching TPTX animals from a low-Pi diet to the high-Pi diet decreased NaPi-2 immunoreactivity from superficial nephrons, but not from juxtamedullary nephrons, within 4 h. These results suggest that dietary Pi could regulate the amount of NaPi-2 protein in the superficial nephrons in a PTH-independent manner.

Animals↗
PubMed1998

Regulation of the PepT1 peptide transporter in the rat small intestine in response to 5-fluorouracil-induced injury.

BACKGROUND & AIMS: The oligopeptide transport system of the small intestine is resistant to mucosal injury. The mechanism of this resistance was investigated by examining the activity level and expression of the peptide transporter PepT1 in the intestine of rats treated with 5-fluorouracil. METHODS: The expression and localization of PepT1 were examined by immunoblot analysis of brush border membrane vesicles and immunohistochemical analysis of intestinal sections with PepT1-specific rabbit polyclonal antibodies. Also, Northern blot analysis was used for the expression of PepT1 messenger RNA (mRNA). RESULTS: Although the amounts of sucrase and an Na+-dependent glucose transporter protein in intestinal vesicles decreased markedly after 5-fluorouracil treatment, the amount of PepT1 protein remained largely unaffected. Immunohistochemical analysis also showed that the PepT1 immunoreactivity level was preserved in the brush border membrane of the remaining villi of 5-fluorouracil-treated rats. Levels of amino acid, glucose, and phosphate transporter mRNAs were profoundly depressed in 5-fluorouracil-treated animals, whereas the level of PepT1 mRNA conversely increased. CONCLUSIONS: The resistance of intestinal peptide transport to tissue injury may be attributable to increased synthesis of PepT1 rather than to a change in the kinetic properties of the residual absorbing cells.

Animals↗
PubMed1998

Chronic renal failure: an overview from a pediatric perspective.

We present data on the costs and impact of chronic renal failure, the primary renal diseases leading to end-stage renal disease in children, and review the adaptive responses and the pathophysiology and complications of uremia in experimental animals and in man. A treatment strategy is summarized.

Adaptation, Physiological↗
PubMed1998

Glomerulosclerosis in the remnant kidney rat is modulated by dietary alpha-tocopherol.

Glomerulosclerosis and tubulointerstitial injury are characteristic features seen in the subtotal (5/6) nephrectomy remnant kidney model in the rat. Oxidative stress from renal mass reduction contributes to the glomerular and tubular injury. Previous studies have clearly demonstrated the prevention or inhibition of such injury by an antioxidant such as alpha-tocopherol. However, few data are available on the ability of alpha-tocopherol to modulate or arrest progression of the established disease. This study examines whether alpha-tocopherol modulates glomerulosclerosis and tubulointerstitial injury when it is given 2 wk after renal damage has been established. The findings indicate that alpha-tocopherol has the capacity to modulate both tubulointerstitial injury and glomerulosclerosis, lower the elevated expression of transforming growth factor-beta1, and reduce plasma and kidney malondialdehyde concentration, the end product of lipid peroxidation. The results support the potential utility of alpha-tocopherol in reversing established glomerulosclerosis and tubulointerstitial injury in a remnant kidney model.

Animals↗
PubMed1998

[Importance of the duration from the onset of a urinary abnormality until a biopsy is performed: a multivariate analysis on the application of renal biopsy for patients with IgA nephropathy].

To clarify the importance of the duration from the onset of a urinary abnormality until a biopsy is actually performed (UA-Bx time) in making a renal prognosis, we investigated 496 patients with IgA nephropathy (male/female: 222/274, mean age: 33.0 +/- 13.7 yrs, mean follow-up period: 10.8 +/- 4.3 yrs). All patients were found to have a urinary abnormality, including both hematuria and proteinuria, at clinical onset while demonstrating a normal renal function, and showing a serum creatinine level of < or = 1.2 mg/dl or a creatinine clearance level of > or = 80 ml/min. The UA-Bx time was divided into 3 groups: < 1 yrs (S-G), 1 < or = < 3 yrs (M-G), > or = 3 yrs (L-G). The severity of glomerular damage was divided into 5 groups based on the occupational rate of segmental sclerotic glomeruli. Based on a multivariate analysis of independent prognostic factors relating to renal death, the severity of glomerular damage was the most independent factor, while the UA-Bx time showed no risk for renal death. However, based on a multivariate analysis of the UA-Bx time regarding the timing of a renal biopsy, patients in L-G, which had the most glomerular damage, showed twice the hazard ratio as those in S-G or M-G and the difference was significant. These results thus indicate that because the glomerular damage is able to progress for 3 yrs or longer after the clinical onset of renal disease, a renal biopsy should therefore be performed within 3 yrs from the clinical onset in patients demonstrating both hematuria and proteinuria when such patients are also suspected of having IgA nephropathy.

Adolescent↗
PubMed1997

Estimation of the numerical densities of neurons and synapses in cerebral cortex.

In this paper we discuss a stereological technique, 'the unfolding method', for a quantitative study of the nervous system [1,31]. Stereology implies a geometric analysis of structures and textures, and is a method to derive directly metric properties of structures from two-dimensional sections on the basis of geometrico-statistical reasoning [36,37]. Recent advances in the stereological method allow quantitative analysis [8,19,27,32]. Images on sections provide only two-dimensional information, but the stereological method can offer three-dimensional and quantitative information [19]. The need for quantitative analysis is more important and useful in the central nervous system (CNS) than in other organs. Two functional units, neurons and synapses, are of particular interest in evaluating CNS function. Numerical densities of neurons and synapses in rat visual cortex were estimated using the unfolding method at light and electron microscopic levels, respectively. Once the numerical densities of neurons and synapses were obtained, synapse-to-neuron ratios could be calculated. The ratios are interpreted as a means to obtain an index of interneuronal connectivity [9]. The unfolding method may become a powerful strategy in neuroscience research when numerical estimates are performed in restricted areas such as cortical layers II-IV, because this method is less time-consuming than other stereological methods [6,21,22].

Animals↗
PubMed1997

Immunohistochemical and RT-PCR detection of Na+-dependent inorganic phosphate cotransporter (NaPi-2) in rat brain.

Expression of a renal Na+-dependent inorganic phosphate (Pi) cotransporter (NaPi-2) was studied in rat forebrain with reverse transcription and polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR analysis for total RNA from whole brain and sequencing of the PCR products showed expression of NaPi-2 mRNA in the brain. Immunohistochemical analysis revealed NaPi-2 staining in many nonpyramidal neurons of all six layers throughout neocortical areas and in neurons of proisocortical and periallocortical areas. NaPi-2-immunoreactive neurons were also detectable in the piriform cortex, hippocampal formation, caudate-putamen, amygdaloid nuclei and lateral geniculate nucleus. Furthermore, NaPi-2 staining was shown in ependymal cells and microvascular endothelial cells. The present results suggest that NaPi-2 is synthesized within the brain and involved in maintaining Pi homeostasis of certain neurons and/or the entire brain.

Animals↗
PubMed1997

Induction of Fos-like immunoreactivity in the lower brainstem and the spinal cord of the rat by intraperitoneal administration of an endogenous satiety substance, 2-buten-4-olide.

Induction of Fos in neurons by intraperitoneal injection of 2-buten-4-olide (2-B40), an endogenous satiety substance, was studied immunohistochemically in the brainstem and spinal cord of the rat. Rats injected intraperitoneally with 2-B40 (100 mg/kg) were allowed to survive for 2 h before perfusion. Fos-like immunoreactivity was observed in neurons of the intermediolateral nucleus, ventral reticular formation, lateral reticular nucleus, nucleus of the solitary tract, locus coeruleus, lateral parabrachial nucleus and dorsal raphe nucleus, as well as in tyrosine hydroxylase-immunoreactive neurons of the cell groups A1, A2, A5, A6, A7, C1, C2 and C3.

4-Butyrolactone↗
PubMed1997

IL-6 and soluble IL-6 receptor levels change differently after surgery both in the blood and in the operative field.

To investigate alterations in post-operative levels of IL-6 and soluble IL-6 receptor (sIL-6R), we examined their levels in serum and samples of drainage fluids from 26 patients who underwent thoracoabdominal surgery. Serum IL-6 levels reached the maximum within the first post-operative day and decreased thereafter. The IL-6 levels in the drainage fluid were much higher than in the serum (458 +/- 101-fold; mean +/- SEM) in the early post-operative phase. A large quantity of sIL-6R levels was present in blood samples. The time course of serum sIL-6R levels in 26 patients showed no significant change. sIL-6R concentrations in the drainage fluid were significantly lower than in serum (4.5 +/- 1.1-fold; mean +/- SEM) in the early post-operative phase. We propose that IL-6 is produced in the operative field and enters the peripheral blood stream to induce elevation of serum IL-6. On the other hand, sIL-6R levels in the operative field are lower than in the serum, and the serum sIL-6R levels are not influenced by surgical trauma. These data suggest that sIL-6R is being constantly produced in areas other than the operative field, while sIL-6R level is reduced by consumption in the operative field. Mechanisms to cope with surgical stress, involving sIL-6R together with its ligand IL-6 may thus exist.

Aged↗
PubMed1997

Acute regulation by dietary phosphate of the sodium-dependent phosphate transporter (NaP(i)-2) in rat kidney.

Alteration of the dietary intake of phosphate (P(i)) leads to rapid changes in renal P(i) transport activity. The present study, examined the underlying cellular mechanisms of the rapid regulation, with special reference to renal P(i) cotransporter. Rats were fed either a low-P(i) (0.02%) diet (CLP rats), the low-P(i) diet followed by a high-P(i) (1.2%) diet (AHP rats), or a normal (0.6%) diet (control rats). Na(+)-dependent P(i) transport activity in the brush border membrane was significantly increased in CLP rats compared with control rats, and this activity decreased rapidly within 2 h after the change of diet in AHP rats. Kinetic analysis of P(i) transport in the AHP rats indicated that the reduction was accompanied by a decrease in the apparent Vmax for Na(+)-dependent P(i) uptake. Northern blot analysis showed no difference in the abundance of NaP(i)-2 mRNA of the kidney between AHP and CLP rats. In contrast, Western blot analysis of renal brush border membrane proteins of AHP rats indicated a significant decrease in the abundance of NaP(i)-2 protein as compared with CLP rats. Immunoreactive signals for NaP(i)-2 were detected in lysosomal fractions of AHP and CLP rats. Immunohistochemical analysis showed that, NaP(i)-2 immunoreactivity in AHP rats was largely reduced in the apical membrane of the proximal tubular epithelial cells. Neither cycloheximide nor actinomycin D affected high-P(i)-induced reduction of NaP(i)-2 protein in the brush border membrane of AHP rats, indicating that de novo protein synthesis of an unidentified regulator protein was not involved in the mechanism of this reduction. In contrast, treatment with colchicine, which disrupts microtubulers, abolished the effect of high-P(i) diet on NaP(i)-2 expression. These results suggested that rapid endocytotic internalization of NaP(i)-2 may occur specifically in the brush border membrane following an acute increase in dietary P(i) intake.

Animals↗
PubMed1997

Elimination of adult T cell leukemia cells by ultrasound in the presence of porfimer sodium.

Sonodynamic effects using porfimer sodium (Photofrin; Pf) on leukemic and normal cells were evaluated. The purpose of this experiment was to compare cell survival among MT-2 cells, normal peripheral mononuclear cells (PMNCs) and adult T cell leukemia (ATL) patients' PMNCs after sonodynamic treatment. Cells were exposed to 450 kHz ultrasound at an intensity of 500 mW/cm2. The survival rate of MT-2 cells exposed to ultrasound alone for 80 s was 20.1 +/- 4.8%, whereas survival rates exposed to ultrasound in combination with 25, 50 and 100 microg/ml of Pf resulted in 11.5 +/- 2.9, 3.2 +/- 1.6 and 1.6 +/- 1.4%, respectively. There was a significant difference of cell survival between the group exposed to ultrasound alone and the Pf-combined groups (n = 6, p < 0.05). On the other hand, in the normal human PMNCs, no significant differences of cell survival rates were found between ultrasound-treated groups with and without Pf. We similarly examined the survival rate of PMNCs in the peripheral blood of five acute-type ATL patients (n = 5) after ultrasound (60 s, 300 mW/cm2) exposure with or without 100 microg/ml of Pf. Comparison of cell survival rate between ultrasound alone and ultrasound plus Pf showed significant differences (69.4 +/- 22.5 and 30.0 +/- 23.0%, respectively). There were no significant cytotoxicities in all Pf alone treated groups of the MT-2 cells, the normal PMNCs and the ATL patients' PMNCs (p < 0.05). It was suggested from this study that there was a specific selectivity of sonodynamic effects to MT-2 cell lines and ATL patients' PMNCs. It is anticipated that this new method of treatment, i.e. sonodynamic therapy, could be used for extracorporeal blood treatment of acute-type ATL patients.

Antineoplastic Agents↗