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Biomedical subjects

Jun Yamada

Publications and source records attributed to Jun Yamada.

At least 55 records · Page 3Linked to original sources

Th2-biased immune system promotion of allogeneic corneal epithelial cell survival after orthotopic limbal transplantation.

PURPOSE: The Th2-biased immune system can promote penetrating keratoplasty survival in mice. A series of experiments were performed to determine whether this system could prolong corneal limbal transplant (LT) survival. METHODS: BALB/c (H-2d) mice were immunized with 50 microg of keyhole limpet hemocyanin (KLH) in incomplete Freud's adjuvant. Four weeks later, the corneal epithelium, including the limbal area, was removed, and the mice received LT from B10.D2 (H-2d), C57BL/10 (H-2b), or enhanced green fluorescence protein (EGFP) transgenic (H-2b) donor mice. Immediately thereafter, recipient mice were immunized with 50 micro g of KLH or Hanks' balanced salt solution (HBSS; control) in complete Freund's adjuvant. The allograft fates were assessed clinically. Lymphocytes of recipients were examined for donor-specific proliferation and for donor-specific cytokine production in vitro. RESULT: The regenerated epithelia of all C57BL/10 (n=14) and B10.D2 (n=18) grafts were rejected swiftly in control mice, whereas 66.6% of C57BL/10 grafts (8/12, P<0.001) and 62.8% of B10.D2 grafts (22/35, P<0.001) in the KLH immune group remained significantly clear for 8 weeks. Moreover, EGFP donor epithelial cells were detected from the healthy corneas of KLH-immunized mice. As for the in vitro assay, at 1 week after B10.D2 grafting, lymphocytes from KLH-immunized groups showed neither proliferation nor increased cytokine secretion. CONCLUSIONS: The Th2-biased immune system can support LT prolongation irrespective of donor disparity and can suppress corneal neovascularization. This prolongation is not due to induction of donor-specific regulatory cells, but is presumably at least associated with the suppression of allosensitization.

Adjuvants, Immunologic↗

The use of frozen autogenous bone flaps in delayed cranioplasty revisited.

OBJECTIVE: To reevaluate the use of frozen autogenous bone flaps for patients undergoing delayed cranioplasty. METHODS: In the past 12 years, 49 patients have undergone delayed cranioplasty using frozen autogenous bone flaps. Bone flaps removed during the initial operation were sealed in three sterilized vinyl bags and stored at -35 degrees C (n = 37) or -84 degrees C (n = 12) for 4 to 168 days (mean, 50.6 d). The bone flaps were thawed at room temperature and replaced in their original positions. After cranioplasty, we monitored resorption of the bone flaps with computed tomography and evaluated the clinical and aesthetic results. Follow-up periods ranged from 14 to 147 months (mean, 59.2 mo). RESULTS: For 47 patients (95.9%), there were no complications during the follow-up period; there was slight thinning of the bone flap in some cases, but clinical and aesthetic results were highly satisfactory. Resorption was observed for a 12-year-old boy who had undergone cranioplasty, using two pieces of bone flap, 66 days after the initial operation. A 14-year-old boy with a cerebral contusion experienced a bone flap infection. Both patients underwent a second cranioplasty procedure, with ceramic plates. CONCLUSION: The clinical and aesthetic results of delayed cranioplasty using frozen autogenous bone flaps were satisfactory. The most important factor for success was excellent contiguity between the flap and the bone edge.

Adolescent↗

Leptin inhibits food intake without affecting brain NOx levels in food-deprived mice.

Effects of leptin on food intake and nitric oxide (NO) metabolites (nitrite and nitrate, NOx) levels of brain were investigated in mice. Leptin dose-dependently decreased milk intake in food-deprived mice. Administration of leptin at a dose of 1 mg/kg, which induces an apparent hypophagia, did not affect NOx levels in the hypothalamus and frontal cortex. These results suggest that leptin reduces food intake in food-deprived mice without altering NO production in the hypothalamus, which plays an important role in regulation of feeding.

Animals↗

Effects of insulin and adrenalectomy on elevation of serum leptin levels induced by 5-hydroxytryptophan in mice.

We previously reported that a serotonin precursor 5-hydroxytryptophan (5-HTP) increases serum leptin levels in mice. In this study, we studied the effects of insulin and adrenalectomy on hyperleptinemia induced by 5-HTP. Co-administration of insulin significantly increased hyperleptinemia elicited by 5-HTP. 5-HTP itself increased serum insulin levels. Adrenalectomy, which depletes corticosterone, did not abolish hyperleptinemic effects of 5-HTP. These results suggest that insulin may participate in hyperleptinemic effects of 5-HTP and that the involvement of corticosterone in effects of 5-HTP may be probably small.

5-Hydroxytryptophan↗

Effects of the serotonergic anxiolytic buspirone on plasma glucose and glucose-induced hyperglycemia in mice.

Effects of the serotonergic anxiolytic buspirone on plasma glucose and glucose-induced hyperglycemia were studied in mice. Buspirone did not affect plasma glucose levels of non-fasted mice, while it increased serum insulin levels. In fasted mice, buspirone significantly reduced glucose-induced hyperglycemia and enhanced insulin release elicited by glucose. This suggests that buspirone enhances insulin release, resulting in inhibition of glucose-induced hyperglycemia. The major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP) increased serum insulin levels and induced a slight hypoglycemia in non-fasted mice. 1-PP decreases glucose-induced hyperglycemia and amplifies insulin release elicited by glucose in fasted mice. Since buspirone is mainly metabolized to 1-PP and formation of 1-PP occurs quickly, the inhibitory effect of buspirone on glucose-induced hyperglycemia is likely mediated by 1-PP.

Animals↗

The tricyclic antidepressant clomipramine increases plasma glucose levels of mice.

Effects of the tricyclic antidepressant clomipramine on plasma glucose levels in mice were studied. Clomipramine at doses ranging 5 - 20 mg/kg elicited significant hyperglycemia in mice. Hyperglycemia elicited by clomipramine was not reduced by pretreatment with the 5-hydroxytryptamine (5-HT) depleter p-chlorophenylalanine. The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it. The 5-HT(2B/2C)-receptor antagonist SB 206553 facilitated hyperglycemia induced by clomipramine, although the 5-HT(2A)-receptor antagonist ketanserin was without effect. Clomipramine-induced hyperglycemia was reduced by prior adrenalectomy. These results suggest that clomipramine induces hyperglycemia in mice by blocking the 5-HT(2B )and/or 5-HT(2C) receptors, which results in facilitation of adrenaline release.

Adrenalectomy↗

Measurement errors in voice-key naming latency for Hiragana.

This study makes explicit the limitations and possibilities of voice-key naming latency research on single hiragana symbols (a Japanese syllabic script) by examining three sets of voice-key naming data against Sakuma, Fushimi, and Tatsumi's 1997 speech-analyzer voice-waveform data. Analysis showed that voice-key measurement errors can be substantial in standard procedures as they may conceal the true effects of significant variables involved in hiragana-naming behavior. While one can avoid voice-key measurement errors to some extent by applying Sakuma, et al.'s deltas and by excluding initial phonemes which induce measurement errors, such errors may be ignored when test items are words and other higher-level linguistic materials.

Adult↗

Articulatory planning in naming single word-kanji characters.

Yamazaki, et al. (1997) rejected word length measured by number of syllables as not significant in accounting for naming latencies for Japanese kanji characters. This study reexamined Yamazaki, et al.'s data and found that monosyllabic characters were named slower than two- and three-syllable characters. This finding is taken as suggesting the presence of an articulatory planning stage in speech production in Japanese.

Adolescent↗

[Clinical study of sarcomatoid renal cell carcinoma].

Patients with sarcomatoid renal cell carcinoma are rare and have poor survival. We evaluated 14 patients who had renal cell carcinoma with a sarcomatoid component between 1982 and 2000. There were 9 men and 5 women with a median age of 59.5 years (range 32 to 77). Seven patients had a tumor on the right side and 7 on the left side. Thirteen patients had some symptoms and 11 had metastases at the initial visit. Most of them were stage T4 and high nuclear grade cancer and showed elevated acute phase reactants. There were 7 patients followed by interferon therapy, and the cause-specific 5-year survival rate was less than 10%. We confirmed that renal cell carcinoma with a sarcomatoid component often showed local invasion, distant metastasis and poor prognosis.

Adult↗

Differential effects of the 5-HT2 receptor antagonist on the anti-immobility effects of noradrenaline and serotonin reuptake inhibitors in the forced swimming test.

The effects of the 5-HT(2) receptor antagonist, LY 53857 on the effects of noradrenaline and serotonin reuptake inhibitors were investigated using the forced swimming test. LY 53857 enhanced anti-immobility effects of clomipramine and maprotiline, which can inhibit reuptake of noradrenaline. However, LY 53857 did not affect the immobility time of mice treated with the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine. These results suggest that antagonism of the 5-HT(2) receptor leads to potentiation of the antidepressant effects of noradrenaline reuptake inhibitors but not SSRIs and that LY 53857 may modify the activity of noradrenergic neurons.

Adrenergic Uptake Inhibitors↗

Increased expression and secretion of r-Gsp protein, rat counterpart of complement C1s precursor, during cyclic AMP-induced differentiation in rat C6 glioma cells.

The gene, termed r-gsp, was originally isolated during identification of differentiation-associated molecules in rat C6 glial cells. Its mRNA expression was markedly increased during cAMP-induced glial cell differentiation. The deduced amino acid sequence of r-gsp was homologous to those of complement C1s precursors of hamsters and humans. In the present study, we raised anti-peptide antibody against r-Gsp protein and analyzed its change during cAMP-induced differentiation. The 90-kDa r-Gsp protein increased time-dependently and reached the maximal level ( approximately 7.6-fold increase) at 24 h in response to dibutyryl cyclic AMP (dbcAMP) and theophylline. Moreover, it was secreted into the medium and then was cleaved to form disulfide-linked fragments, one of which was 30 kDa, similar to C1s, suggesting its processing in the extracellular space. In fact, the partially purified r-Gsp from culture medium was cleaved by active human C1r to form a 30-kDa polypeptide. Moreover, secreted r-Gsp protein cleaved human C4alpha to yield C4alpha' and associated with human serum C1-esterase inhibitor, strongly suggesting that r-Gsp protein is rat C1s. However, in C6 cells overexpressing r-Gsp, their morphology and proliferation rate were similar to those in parent C6 cells. These results suggest that r-Gsp protein could not induce glial differentiation alone, and suggest that r-Gsp protein was secreted as a proenzyme and processed in culture medium. Its possible role in glial cell differentiation will be discussed.

Animals↗

Nitric oxide production in hypothalamus of 2-deoxy-D-glucose-treated and food deprived mice.

Nitric oxide (NO) has been suggested to be involved in the regulation of food intake. In the present study, NO metabolite (nitrite and nitrate, NOx) levels in the hypothalamus were determined in hyperphagic mice. In normal mice, NOx levels were higher in the hypothalamus than those in frontal cortex. Although 2-deoxy-D-glucose (2-DG) is known to induce hyperphagia by inhibiting glucose utilization, it did not affect NOx levels in the hypothalamus of mice. NOx concentration in the hypothalamus decreased in 48 h-food deprived mice. In the frontal cortex, neither 2-DG nor food deprivation affected NOx levels. These results suggest that NO production in the hypothalamus does not increase in 2-DG-elicited hyperphagia and that food deprivation reduces hypothalamic NO, probably by inhibiting NO synthase.

Animals↗

Acid sphingomyelinase activation requires caspase-8 but not p53 nor reactive oxygen species during Fas-induced apoptosis in human glioma cells.

During apoptosis of human glioma cells induced by anti-Fas antibody, ceramide formation with activation of acid, but not neutral sphingomyelinase (SMase), was observed. A potent inhibitor of acid SMase, SR33557, effectively inhibited ceramide formation and apoptosis. Fas-induced apoptosis and ceramide formation proceeded regardless of p53 status. The agents, which modify intracellular levels of reactive oxygen species (ROS) and reduced glutathione (GSH), failed to modulate Fas-induced acid SMase activation and apoptosis. Moreover, expression of functional p53 protein using a temperature-sensitive human p53val(138) induced ceramide generation by activation of neutral SMase but not acid SMase through ROS formation. Peptide inhibitors for caspases-8 (z-IETD-fmk) and -3 (z-DEVD-fmk) suppressed Fas-induced apoptosis. However, activation of acid SMase was inhibited only by z-IETD-fmk. Thus, ceramide generated by acid SMase may take a part in Fas-induced apoptosis of human glioma cells and acid SMase activation may be dependent on caspase-8 activation, but not on p53 nor ROS.

Apoptosis↗

Neurological origins of poor reading comprehension despite fast word decoding?

Barnes, Faulkner, and Dennis (2001) found that hydrocephalic children (mean age = 11.5 years) of average or above-average verbal intelligence exhibit poor reading comprehension despite their fast and accurate decoding skills on individual words. This finding attracts the attention of reading researchers because it appears to be against the following standard principle of reading comprehension failure (Gough & Hillinger, 1980), thereby provoking basic issues centering around it (e.g., Stanovich, 1991): Reading Comprehension = Word Decoding x Listening Comprehension. This formula indicates that when listening comprehension is kept well within the normal range, reading comprehension is highly correlated with word decoding (e.g., Perfetti, 1985). In contrast, with poor listening comprehension children would be poor readers however good they may be at reading words (e.g., Cain, Oakhill, & Bryant, 2000). Although Barnes et al. clearly demonstrated that children with hydrocephalus decoded individual words better than they comprehended text, it is not readily apparent whether their findings are inconsistent with the standard principle. The purpose of the present article is twofold. The first is to examine whether Barnes et al.'s findings constitute a counterexample of the above principle. (Note that Barnes et al. did not address this question.) The second and more important purpose is to discuss the possible origins of the decoding-better-than-sentence/text-comprehension pattern. We also present some pedagogical implications for poor readers such as hydrocephalic children.

Child↗

Prolonged anti-inflammatory action of DL-lactide/glycolide copolymer nanospheres containing betamethasone sodium phosphate for an intra-articular delivery system in antigen-induced arthritic rabbit.

PURPOSE: The objective of the present study was to develop prolonged anti-inflammatory action of DL-lactide/glycolide copolymer (PLGA) nanosphere incorporating a water-soluble corticosteroid (betamethasone sodium phosphate; BSP). Another aim was to demonstrate the biocompatibility and biologic efficacy of these BSP-loaded nanospheres directly administered into ovalbumin-induced chronic synovitis in the rabbit. METHODS: BSP-loaded nanospheres were prepared by an emulsion solvent diffusion method in oil (caprylate and caprate triglyceride). The drug releasing properties of the nanospheres were measured in vitro in phosphate buffer saline (PBS: pH7.4), and in vivo in rat air-pouch (pseudo synovial fluid). The BSP-loaded nanosphere suspensions were administered into the joint cavity in a model of antigen-induced arthritic rabbit and evaluated by measuring the joint swelling, and the biocompatibility was appraised by histologic microscopy. RESULTS: The BSP-nanospheres were a unimodally-dispersed particulate system with a mean diameter ranging from 300 to 490 nm, and BSP was efficiently entrapped in the lipophilic copolymer (PLGA), although its hydrophilic properties. The drug release-rate from the nanospheres in PBS was controlled by the molecular weight and the lactic/glycolic acid (LA/GA) ratio of the polymers. The in vitro releasing study demonstrated that sustained drug release occurred for over three weeks. In the antigen-induced arthritic rabbit, the joint swelling decreased significantly by administering BSP-loaded nanospheres during a 21-day period after intra-articular challenge. With regards to the prolonged anti-inflammatory efficacy, serum antibody to ovalbumin showed a sustained reduction during the period, and the steroidal effect appeared by the degradation of the polymer in the synovium. The BSP-nanosphere administered was phagocytosed by the synovial activated-cells and the cartilage degradation was almost prevented. CONCLUSIONS: Direct intra-articular injection of a PLGA nanosphere system with a water-soluble steroid provided a prolonged pharmacological efficacy in the joints of arthritic rabbits. The local anesthetic in the knee-joints was evaluated to be safe and without biologic damage.

Animals↗

Effects of peripheral administration of 5-hydroxytryptamine (5-HT ) on 2-deoxy-D-glucose-induced hyperphagia in rats.

Effects of peripheral administration of 5-HT (5-hydroxytryptamine, serotonin) on hyperphagia induced by 2-deoxy-D-glucose(2-DG) were studied in rats. It was found that 5-HT i.p. reduced 2-DG-elicited feeding in rats dose-dependently. The 5-HT-induced hypophagia was antagonized by the 5-HT2A receptor antagonist, ketanserin. It is known that 2-DG induces glucoprivation, resulting in hyperphagia and hyperglycemia. However, 5-HT did not affect hyperglycemia induced by 2-DG. These results suggest that peripheral injection of 5-HT reduces 2-DG-induced hyperphagia mediated by the peripheral 5-HT2A receptor and that its effects are not due to enhancement of hyperglycemia.

Animals↗

The 5-HT2 receptor antagonist reduces immobility of mice treated with the atypical antidepressant mianserin in the forced swimming test.

Effects of co-administration with the 5-HT(2) receptor antagonist LY 53857 and the antidepressant mianserin on immobility time in the forced swimming test were investigated in mice. Mianserin did not affect the immobility time at ranges from 1-10 mg/kg, although it elicited anti-immobility effects at 20 mg/kg. Co-administration of the 5-HT(2) receptor antagonist LY 53857 and a subactive dose of mianserin induced apparent anti-immobility effects. Since mianserin facilitates noradrenaline (NA) release from nerve terminals via inhibition of alpha(2) receptors, the blockade of the 5-HT(2) receptor may increase the antidepressant effect of drugs modifying NA levels in the synaptic cleft.

Animals↗