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Biomedical subjects

H Nishioka

Publications and source records attributed to H Nishioka.

At least 19 recordsLinked to original sources
PubMed2006

Effect of morphine on the release of excitatory amino acids in the rat hind instep: Pain is modulated by the interaction between the peripheral opioid and glutamate systems.

Behavioral evidence supports a role for peripheral glutamate receptors in normal nociceptive transmission. In this study, we examined the release of the excitatory amino acids, glutamate and aspartate, in the s.c. perfusate of the rat hind instep by in vivo microdialysis. Antidromic stimulation of the sciatic nerve and noxious stimuli in the form of heat stimulation and local application of capsaicin cream (1%) to the instep caused an increase in excitatory amino acid release. This capsaicin-induced excitatory amino acid release was suppressed by pretreatment with capsaicin. Both systemic (10 mg/kg, i.v.) and local injections (10(-5) M in the perfusate) of morphine inhibited the increase in excitatory amino acid release evoked by local application of capsaicin cream to the instep. This inhibitory effect of morphine was antagonized by naloxone either given systemically (5 mg/kg, i.v.) or locally (10(-5) M). These results suggest that excitatory amino acids are released from small diameter afferent fibers by heat stimulation in the periphery or local application of capsaicin cream, and that activation of opioid receptors, present on the peripheral endings of small-diameter afferent fibers, can regulate noxious stimulus-induced excitatory amino acid release.

Analgesics, Opioid↗
PubMed2006

Management of intracranial germ cell tumors presenting with rapid deterioration of consciousness.

OBJECTIVES: The value of surgical intervention in the management of intracranial germ cell tumors remains controversial. PATIENTS: We report three patients who presented with rapid deterioration of consciousness but resulted in complete remission of the tumor after emergency surgery for both diagnostic (biopsy) and therapeutic (for hydrocephalus) purposes followed by prompt initiation of radiochemotherapy. CONCLUSION: For management of these rapidly deteriorating patients, immediate histological verification and avoidance of delay in the induction of radiochemotherapy are essential. Thus, emergency surgery with a less invasive procedure is the first choice of treatment, i. e., endoscopic surgery for pineal region tumor and CT-guided biopsy for basal ganglia tumor.

Adult↗
PubMed2005

Risk factors of cerebrospinal fluid rhinorrhea following transsphenoidal surgery.

OBJECTIVE: Cerebrospinal fluid (CSF) rhinorrhea is a potentially life-threatening complication following transsphenoidal surgery (TSS). METHODS: To elucidate the risk factors that may affect the incidence of postoperative CSF rhinorrhea, we retrospectively reviewed 200 consecutive cases of TSS performed by a single surgeon for 168 adenomas and 32 other sellar and parasellar lesions. RESULTS: Intra-operative CSF leakage was encountered in 38 cases (19.0%). Its incidence did not correlate to tumor size. Among 4 microadenoma cases with CSF leak, 3 were ACTH adenomas. In contrast, postoperative CSF rhinorrhea was observed in 5 cases (2.5%), all following TSS for adenomas. It was frequently noted in cases with prior TSS (3/40, 7.5%, p = 0.0235) and prior radiotherapy (2/7, 28.6%, p < 0.0001). Two cases who required surgical intervention had received TSS and radiotherapy previously. CONCLUSION: The risk of postoperative CSF rhinorrhea is significantly increased in cases with prior TSS or radiotherapy or both. In addition, these cases tended to show delayed CSF leaks and require sellar reconstruction for its treatment. When a CSF leak was encountered during TSS in these high-risk cases, thorough sellar reconstruction and long-term follow-up is necessary.

Adenoma↗
PubMed2005

Hypopituitarism and anemia: effect of replacement therapy with hydrocortisone and/or levothyroxine.

Although common, anemia associated with hypopituitarism has received little attention. We conducted a retrospective study to elucidate the effect of replacement therapy with hydrocortisone and/or levothyroxine on the decreased hemoglobin (Hb) level. A total of 68 patients who had been suffering from anterior pituitary deficiencies for more than 12 months were studied. The Hb level was significantly lower in patients with hypopituitarism (p=0.0012). Decreased Hb level (<12.0 g/dl) was observed in 22 patients (32.4%). It was related to hypocortisolism (regression weights=0.39), hypothyroidism (0.37), GHD (0.32) and hypogonadism in men (0.17). Among 68 patients, 30 patients had been receiving replacement therapy for at least 12 months. Hydrocortisone and levothyroxine increased the Hb level in 20 patients whose data were available before the replacement (p=0.0002). However, the Hb level was still lower in 30 patients receiving the replacement (p=0.0001). In 13 patients (8 men) with decreased Hb level (<12.0 g/dl) despite the replacement, GH and testosterone were deficient in 12 (92.3%) and 8 (100%) patients, respectively. In conclusion, replacement therapy with hydrocortisone and/or levothyroxine is effective in most patients but is not sufficient, at least in some patients, to improve the decreased Hb level. These results suggest that additional replacement therapy, i.e. with GH and/or androgen, is necessary to obtain further improvement.

Adult↗
PubMed2002

Gender-related differences in prolactin secretion in pituitary prolactinomas.

In pituitary prolactinomas, serum prolactin (PRL) levels usually parallel the tumor size. We conducted a retrospective study to determine differences in PRL production between men and women with prolactinomas. A total of 51 patients, 16 men and 35 women, was studied. We investigated clinical, endocrinological, radiological and histological findings, and estimated the tumor volume (TV) by high-resolution magnetic resonance imaging (MRI). Correlation between PRL level and TV was low in men (R=0.458), in contrast to women (R=0.953), c. Men with prolactinomas showed predominance of large tumors (P=0.0009) with high PRL levels (P=0.0009) and had greater tendencies for cyst formation (P=0.0047). Large prolactinomas tended to be accompanied by cyst(s) (P=0.0051) and hemorrhage ( P=0.0015), both of which were associated with reduced PRL secretion (P=0.0004 and P<0.0001, respectively). When the volume of the cysts and hemorrhage was subtracted from the total TV, correlation between PRL level and TV became greater (R=0.905) with no gender difference. Histological examination demonstrated a sparsely granulated type of lactotroph adenoma with occasional fibrosis, particularly in tumors with hemorrhage and cysts. Although a significant discrepancy between PRL level and TV may exist in prolactinomas when intratumoral hemorrhage and/or cysts are present, there is no essential difference in PRL secretion between the sexes.

Adolescent↗
PubMed2002

Urinary excretion of selegiline N-oxide, a new indicator for selegiline administration in man.

1. The metabolism of selegiline (SG) has been studied by investigating the time-course of urinary excretion of SG and its metabolites using high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS) in combination with solid-phase extraction. 2. The excretion profiles of SG and its four major metabolites, selegiline-N-oxide (SGO), N-desmethylselegiline (DM-SG), methamphetamine (MA) and amphetamine (AP), were investigated in six healthy volunteers after oral administrations of SG hydrochloride in a single dose of 2.5 or 7.5mg, and a repeat twice-daily dose of 5.0 mg day(-1) (for 3 days). 3. The cumulative amount of SGO excreted within approximately the first 8-12h was comparable with MA, and the amount in the first 72 h was 2.0-7.8 times larger (2.8-13.2% of the dose) than that of DM-SG. 4. These results demonstrate that SGO can be used in place of DM-SG, which is known to be a main specific metabolite of SG, as a new indicator for the discrimination of SG use compared with MA abuse.

Adrenergic Uptake Inhibitors↗
PubMed2001

Identification of protein kinase Calpha as an essential, but not sufficient, cytosolic factor for Ca2+-induced alpha- and dense-core granule secretion in platelets.

Upon activation, platelets release many active substances. Here, we have analyzed the mechanism governing Ca(2+)-induced secretion of von Willebrand factor stored in alpha-granules and 5-hydroxytryptamine in dense-core granules in permeabilized human platelets. Both secretions were dependent on ATP and cytosol. An essential factor for both granule secretions was purified from rat brain cytosol and identified to be protein kinase Calpha (PKCalpha) by partial amino acid sequencing. Purified PKCalpha efficiently stimulated both secretions in the presence of cytosol, whereas PKCalpha alone did not support the secretion of either type of granules, suggesting that PKCalpha is not a sufficient factor. Finally, in human platelet cytosol fractionated by a gel filtration column, the stimulatory activity for dense-core granule secretion paralleled with the concentration of PKC, suggesting that PKC could also be such a stimulatory factor in platelet cytosol. Thus, we identified PKCalpha as an essential, but not sufficient, cytosolic factor for the Ca(2+)-induced secretions of both alpha- and dense-core granules in platelets.

Adenosine Triphosphate↗
PubMed2001

Small GTPase Rho regulates thrombin-induced platelet aggregation.

Platelets play essential roles in hemostasis and thrombosis by aggregating with each other. However, the molecular mechanism governing platelet aggregation is not yet fully understood. Here, we established an assay system using platelets permeabilized with streptolysin-O to analyze mechanism of the thrombin-induced aggregation, focusing upon a controversial issue in the field whether small GTPase Rho regulates the aggregation. Incubation of the permeabilized platelets with Rho GDP-dissociation inhibitor, an inhibitory regulator for Rho family GTPases, extracted Rho family proteins extensively from the plasma and intracellular membranes, and inhibited the thrombin-induced aggregation. Incubation of the permeabilized platelets with botulinum exoenzyme C3, which specifically inhibits Rho function by ADP-ribosylating it, abolished the thrombin-induced aggregation. Thus, Rho is involved in thrombin-induced aggregation of platelets.

ADP Ribose Transferases↗
PubMed2001

Mut-Test to detect substances suppressing spontaneous mutation due to oxidative damage.

Since it has been considered that suppression of spontaneous mutation in cells is related to suppression of spontaneous carcinogenesis, it is significant to detect substances which suppress spontaneous mutation in bacterial cells such as Escherichia coli and Salmonella typhimurium in the environment. However, since the frequency of spontaneous mutation in bacteria is usually very low, generally 10(-8)-10(-10),it is difficult to determine significant suppressive ability of such substances on spontaneous mutation. A new method, Mut-Test, was developed by us, applying Luria & Delbruck fluctuation test, to detect substances which suppress spontaneous mutation using E. coli mutT mutant in which spontaneous mutation frequency due to oxidative damage is enhanced to approximately 500-1000 times of the wild type strain. Suppressive abilities of two hydroxyl radical scavengers: D(-)-mannitol and thiourea, were examined and clear positive results were obtained, suggesting that the radical scavengers are suitable as the positive control for the test. Using Mut-Test, suppressive abilities of four vitamins: L-ascorbic acid, beta-carotene, folic acid and riboflavin; 10 polyphenols: caffeic acid, ellagic acid, (-)-epicatechin, (-)-epicatechin gallate, (-)-epigallocatechin, gallic acid, pyrocatechol, pyrogallol, quercetin and tannic acid which are recognized as antimutagens, were examined. Furthermore, the concentrations for 50% of suppressive abilities of five positive samples, L-ascorbic acid, folic acid, caffeic acid, pyrocatechol and pyrogallol were compared. Negative results were obtained in nine samples, riboflavin, tannic acid, etc. suggesting that their antimutagenic effect on cells may not be related to oxidative damage in cells.

Antimutagenic Agents↗
PubMed2001

Growth potential of female prolactinomas.

BACKGROUND: The indications for treatment in female patients with small prolactinomas and mild or no symptoms are controversial. The aim of this study was to investigate whether we can predict the growth potential of a given small prolactinoma. METHODS: The proliferation potential of 25 female prolactinomas and 5 prolactin-containing adenomas found incidentally at autopsy was determined immunohistochemically using the Ki-67 (MIB-1) antibody. The results were compared according to age, clinical and endocrine findings, and tumor volume. RESULTS: Small prolactinomas (<1.0 cm(3)) with mild hyperprolactinemia (<150 ng/mL) showed significantly low proliferation potential irrespective of age, resembling prolactin-containing adenomas found at autopsy. The patients tended to present with mild symptoms and rarely had estrogen deficiency. CONCLUSION: These findings indicate that female patients with a small prolactinoma, mild hyperprolactinemia, and no symptoms or those who do not desire fertility may have no specific reason for treatment, but can be followed by serum prolactin level and serial magnetic resonance imaging.

Adolescent↗
PubMed2001

Histological changes in the hypofunctional pituitary gland following conventional radiotherapy for adenoma.

AIMS: Although delayed hypopituitarism is a common complication of conventional radiotherapy of sellar tumours, histological changes that may account for it have been rarely reported. To elucidate the changes, hypofunctional pituitary glands following irradiation were studied. METHODS AND RESULTS: Two pituitary glands obtained at autopsy from patients who had been irradiated for adenoma and exhibited hypopituitarism were examined. In both cases diffuse fibrosis was observed in the adenohypophysis, whereas the neurohypophysis remained unchanged. Immunohistochemistry showed that stellate-shaped S100 protein-positive cells were increased in number and distributed among the endocrine cells. Some irradiated endocrine cells showed dense granular immunoreactivity for mitochondrial protein, cytochrome oxidase and manganese-superoxide dismutase. In addition to faint reactivity with anti-cytokeratin 8, 18 antibody, many cells were densely positive with anti-cytokeratin 1, 5, 10, 14 antibody. CONCLUSIONS: These results indicate that radiation- induced fibrosis is associated with an increased number of folliculo-stellate cells and the presence of metabolic dysfunctional mitochondria resembling mitochondria in oncocytes. Squamous metaplasia in the irradiated endocrine cells was also noted. Various intracellular changes may participate in delayed pituitary hypofunction following radiotherapy.

Adenoma↗
PubMed2001

Cerebral vasospasm following transsphenoidal removal of a pituitary adenoma.

We report a case of pituitary macroadenoma that developed symptomatic vasospasm 12 days after transsphenoidal removal, but showed an excellent recovery following active treatment identical to those for vasopasm following aneurysmal subarachonid haemorrhage. Subarachnoid haematoma in the basal cisterns secondary from postoperative intracapsular haemorrhage was the most probable cause of the vasopasm.

Adenoma↗
PubMed2001

Molecular dissection of alpha- and dense-core granule secretion of platelets.

Upon activation, platelets release many active substances stored in alpha- and dense-core granules. However, the molecular mechanisms governing the regulated exocytosis are not yet fully understood. We have established an assay system using streptolysin-O-permeabilized platelets to analyze the Ca2+-induced secretions of von Willebrand factor stored in alpha-granules and [3H]5-hydroxytryptamine (5-HT) in dense-core granules. Using the assay, we found that small GTPase Rab4 regulates alpha-, but not dense-core, granule secretion in platelets. Furthermore, we purified a cytosolic essential protein and currently are analyzing its function.

Blood Platelets↗
PubMed2001

Analysis of core promoter sequences located downstream from the TATA element in the hsp70 promoter from Drosophila melanogaster.

TFIID recognizes multiple sequence elements in the hsp70 promoter of Drosophila. Here, we investigate the function of sequences downstream from the TATA element. A mutation in the initiator was identified that caused an eightfold reduction in binding of TFIID and a fourfold reduction in transcription in vitro. Another mutation in the +24 to +29 region was somewhat less inhibitory, but a mutation in the +14 to +19 region had essentially no effect. The normal promoter and the mutants in the initiator and the +24 to +29 region were transformed into flies by P element-mediated transformation. The initiator mutation reduced expression an average of twofold in adult flies, whereas the mutation in the +24 to +29 region had essentially no effect. In contrast, a promoter combining the two mutations was expressed an average of sixfold less than the wild type. The results suggest that the initiator and the +24 to +29 region could serve overlapping functions in vivo. Protein-DNA cross-linking was used to identify which subunits of TFIID contact the +24 to +29 region and the initiator. No specific subunits were found to cross-link to the +24 to +29 region. In contrast, the initiator cross-linked exclusively to dTAF230. Remarkably, dTAF230 cross-links approximately 10 times more efficiently to the nontranscribed strand than to the transcribed strand at the initiator.

Animals↗
PubMed2001

Serum levels of advanced glycosylation end products in diabetic nephropathy.

BACKGROUND/AIMS: Advanced glycosylation end products (AGEs) are important pathogenetic factors underlying diabetic complications. Recently, a highly reliable new enzyme-linked immunosorbent assay for these metabolites has been established. We used the assay to correlate AGEs in serum with renal function categories and histopathology in patients with diabetic nephropathy. METHODS: Type 2 diabetic patients (n = 71) and healthy control subjects (n = 35) were studied. The diabetic subjects were divided into two groups: normal renal function and chronic renal failure not requiring dialysis. In renal biopsy specimens from 22 diabetic subjects with a normal renal function, the severity of glomerular lesions was assessed morphometrically in terms of the ratio of the area of periodic acid-Schiff stained mesangium to total glomerular area. RESULTS: The serum AGE concentrations were higher in both undialyzed diabetic groups, especially in those with renal failure, than in the controls. The serum AGE concentrations increased with the severity of glomerular lesions (morphometric ratio under 15%, 2.85 +/- 0.73 mU/ml; 15-24%, 4.01 +/- 0.71 mU/ml; 25% or more, 5.12 +/- 0.64 mU/ml). CONCLUSIONS: The serum AGE levels measured by the new enzyme-linked immunosorbent assay reflected the severity of glomerulopathy, and, therefore, it may be a clinically useful tool for assessing diabetic renal complications.

Adult↗