Biomedical subjects

J Nakamura

Publications and source records attributed to J Nakamura.

At least 253 records · Page 14Linked to original sources

PubMed1996

Enhancement and inhibition of mitogenic action of insulin-like growth factor I by high glucose in cultured bovine retinal pericytes.

To explore the possible relationship between insulin-like growth factor I(IGF-I) and diabetic retinopathy, we examined the effects of glucose on IGF-I stimulated thymidine incorporation into DNA and IGF-I binding in cultured bovine retinal pericytes. IGF-I significantly increased thymidine incorporation, and its effect was completely inhibited by IGF-I receptor antibody. The exposure to high glucose for 8 h significantly enhanced the IGF-I induced increase in thymidine incorporation as compared with those to normal glucose and to high osmolarity. In contrast, the incubation with high glucose for 24 h decreased thymidine incorporation in response to IGF-I. Specific binding of IGF-I to pericytes was increased by the incubation with high glucose for both 8 and 24 h. These results suggest that glucose may play an important role in the regulation of mitogenic action of IGF-I in retinal pericytes.

Animals↗

PubMed1996

Topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of spontaneously epileptic rats (SER).

The spontaneously epileptic rat (SER), a double mutant, manifests both tonic and absence-like seizures. The effect of topiramate, a novel antiepileptic drug, on the extracellular levels of excitatory amino acids (EAA) in the hippocampus of SER was investigated using in vivo microdialysis. The basal levels of glutamate and aspartate in dialysates of hippocampus in SER were 2- to 3-fold higher than those in normal Wistar rats. Both the dose-response relationship and the time course of the suppression of tonic seizures by topiramate were similar to the attenuation of glutamate level in SER. Topiramate (40 mg/kg i.p.) significantly (P < 0.05) reduced both glutamate and aspartate levels in SER while showing no effect on normal Wistar rats. These findings suggest that topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of SER. This effect may, at least in part, be related to the anticonvulsant activity of topiramate.

Animals↗

PubMed1996

Long-term patterns of change in ERPs across repeated measurements.

Ten subjects were tested for eight sessions using an auditory oddball paradigm at 1-week and 1-month intervals to examine the stability of multiple event-related potential (ERP) components, in terms of trait (between session) and state (within session) reliability. The between session reliabilities presented as intraclass correlations (r') were 0.54 for the P300 amplitude and 0.47 for the P300 latency. Pearson correlation coefficients, representing within-session reliabilities, ranged from 0.54 to 0.68 for P300 amplitude and 0.12 to 0.46 for P300 latency. Statistical analysis of results from the eight sessions demonstrated that session-dependent reduction and recovery of the P300 amplitude occurred during the testing sessions. Other ERPs measurements such as N100-P300, N200-P300, N100, and N200 amplitudes did not exhibit any significant changes. The between- and within-session reliabilities of P300 components suggest that P300 may be a reproducible biological marker of state and trait even across repeated measurements. We speculate that the observed long-term patterns of change in P300 may have reflected habituation and dishabituation of certain processes in the human central nervous system.

Adult↗

PubMed1996

Effect of a novel hypoglycemic agent, KAD-1229 on glucose metabolism and fructose-2,6-bisphosphate content in isolated hepatocytes of normal rats.

The effects of a novel hypoglycemic agent, calcium(2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate dihydrate (KAD-1229), which is a benzyl succinate derivative, on liver metabolism were investigated using isolated hepatocytes from normal rats. In the presence of 10 mM glucose, KAD-1229 increased the L-lactate production (41.1 +/- 0.9 versus 60.9 +/- 2.6 mumol of lactate/g of cells/30 min; P < 0.05) and inhibited gluconeogenesis in hepatocytes (0.94 +/- 0.02 versus 0.70 +/- 0.03 mumol of [2-14C]-pyruvate converted to glucose/g of cells/20 min; P < 0.05). These effects by KAD-1229 were accompanied by an increase in the cellular content of fructose-2,6-bisphosphate (F-2,6-P2), which is one of the important regulators of hepatic glucose metabolism, in a dose-dependent manner (0.05-2.5 mM). KAD-1229 also stimulated the oxidation of [2-14C]-pyruvate and [6-14C]-glucose in the tricarboxylic acid cycle (+18 and +31%, respectively), indicating that stimulation of tricarboxylic acid cycle activity and/or enhancement of the glycolytic flux rate had occurred. Moreover, KAD-1229 did not modify the activities of 6-phosphofructo 2-kinase or fructose-2,6-bisphosphatase, but increased significantly the accumulation of fructose 6-phosphate in hepatocytes. These results suggest that KAD-1229 has extrapancreatic effects on hepatic glucose metabolism, that its actions are mediated through the inhibition of fructose-1,6-bisphosphatase and stimulation of both the 6-phosphofructo 1-kinase reaction and tricarboxylic acid cycle activity by increasing the F-2,6-P2 content in hepatocytes, and that these multiple effects may account in part for the ability of KAD-1229 to reduce blood glucose levels in vivo.

Analysis of Variance↗

PubMed1996

In situ ocular absorption of tilisolol through ocular membranes in albino rabbits.

The purpose of this study is to characterize the in situ absorption properties of ocular membranes using a cylindrical cell. Drug disappearance in the cell was determined as in situ absorption after an application of drug solution into the cell on the comea, sclera (bulbar conjunctiva and sclera layer), or palpebral conjunctiva. Tilisolol was used as a model of an ophthalmic beta-blocker. Tilisolol disappeared from the conjunctival and scleral surfaces although hardly any disappearance of tilisolol from the corneal surface was observed. Depletion of drug from the precorneal space was much faster in situ than extrapolated from permeability measurements (in vitro) of the separate tissues. This may arise from an influence of blood flow. The in situ apparent permeability coefficient of tilisolol through the conjunctiva was almost constant at various concentrations of drug (5-100 mM), suggesting a passive diffusion of tilisolol that was affected by medium pH. A high concentration of tilisolol in the aqueous humor was observed in the corneal application although the scleral and conjunctival applications showed a slight concentration of tilisolol. The corneal route was a dominant route of access to the aqueous humor. Access to the vitreous body for tilisolol was 4 times more effective through the sclera than through the cornea. On the other hand, the corneal application showed an extremely low concentration of tilisolol in plasma compared to the scleral and conjunctival applications. Thus, the in situ method using a cylindrical cell is a useful method for investigation of the ocular absorption of ophthalmic drugs.

Absorption↗

PubMed1996

Adenosine A2a receptor-mediated modulation of striatal acetylcholine release in vivo.

To determine the functions of striatal adenosine A2a receptors in vivo, the effects of a selective agonist, 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethyl-carboxamidoaden osi ne hydrochloride (CGS 21680), and an antagonist, (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (KF17837), on acetylcholine release were investigated in the striatum of awake freely moving rats using microdialysis. Intracerebroventricular injection of CGS 21680 (10 micrograms) increased acetylcholine release in striatum and KF17837 (30 mg/kg p.o.) antagonized the CGS 21680-induced acetylcholine elevation. To investigate the contribution of dopaminergic and GABAergic neurons on A2a receptor-mediated acetylcholine release, the effects of CGS 21680 were studied by using dopamine-depleted rats in the presence or absence of GABA antagonists. In the dopamine-depleted striatum, the intrastriatal application of CGS 21680 (0.3-30 microM) increased extracellular acetylcholine, which was significantly greater than that in normal striatum. The CGS 21680-induced elevation of acetylcholine release was still observed in the presence of GABA antagonists bicuculline (30 microM) and 2-hydroxysaclofen (100 microM) and was similar in both normal and dopamine-depleted striatum. These results suggest that A2a agonist stimulates acetylcholine release in vivo, and this effect of A2a agonist is modulated by dopaminergic and GABAergic neurotransmission.

Acetylcholine↗

PubMed1996

Change in the expression of hypopharyngeal-gland proteins of the worker honeybees (Apis mellifera L.) with age and/or role.

The roles of adult worker honeybees change with age; young workers nurse brood by secreting bee milk (royal jelly), and older workers forage for nectar and pollen and process nectar into honey. The electrophoretic profile of worker hypopharyngeal-gland proteins changes with age and/or role. Immunoblotting analysis using affinity-purified antibodies against three major proteins (50, 56, and 64 kDa) of the nurse-bee gland showed that they are synthesized selectively and secreted as bee-milk proteins. Immunofluorescence study showed that the proteins condense in the duct after secretion from acini. However, a major 70-kDa protein synthesized specifically in the forager-bee hypopharyngeal gland was identified as an alpha-glucosidase. Therefore, the hypopharyngeal gland seems to have two distinct states differentiated by synthesizing of different major proteins depending on the age-dependent role change.

Aging↗

PubMed1996

Protection of scallop sarcoplasmic reticulum ATPase from thermal inactivation by removal of calcium from high-affinity binding sites on the enzyme.

Sarcoplasmic reticulum (SR) vesicles were isolated from scallop muscle by the method of Abe et al. (J. Biochem. 112, 822-827, 1992) and their thermolability was examined in the presence and absence of Ca2+. When SR was preincubated at 38 degrees C in the presence of 0.1 mM Ca2+, Ca2+ transport activity decreased as a function of time with a half-inhibition time of about 5 min. Activities of the Ca(2+)-dependent ATPase, phosphoenzyme (EP) formation and E2 to E1 transition were decreased by the heat treatment in parallel with the Ca2+ transport activity. In contrast, when SR was preincubated at 38 degrees C in the presence of 2-5 mM EGTA, all of these activities, except for the Ca2+ transport, were markedly protected from the heat inactivation. The uncoupling between Ca2+ transport and the ATPase reaction did not lead to a rise in the Ca2+ permeability of SR membrane. Plots of the ATPase activity or steady-state level of EP against pCa in the thermal incubation medium revealed a typical sigmoidal curve with a half-inhibition concentration and Hill number of about 0.5 microM and 1.80, respectively. These results suggest that 2 mol of Ca2+ must be removed from the high-affinity Ca2+ binding sites on the ATPase to stabilize the Ca(2+)-ATPase against heat inactivation. The protection from heat inactivation disappeared if SR was preincubated at 38 degrees C after having been solubilized with a nonionic detergent, but returned when the detergent was removed to reconstitute the SR membrane. These results suggest that the protection of ATPase from thermal inactivation in EGTA may require a membrane structure in which the ATPase molecules exist in an appropriate arrangement.

Adenosine Triphosphate↗

PubMed1996

Leukemoid reaction in epidermal squamous cell carcinoma.

There have been no previous concrete reports of leukemoid reactions associated with squamous cell carcinoma originating in cutaneous tissue. Here we report a case of epidermal squamous cell carcinoma of the sacral region and an associated leukemoid reaction. The tumor invaded deeply and destroyed both the sacrum and coccyx. The white blood cell count was greater than 20,000/mm3. After resection of the tumor, white blood cells transiently decreased, but did not fall under 10,000/mm3. Post-operative infection by methicillin-resistant Staphylococcus aureus and Bacteroides caccae caused sepsis and further elevation of the leukocytes to greater than 50,000/mm3. The leukemoid reaction in the case appeared to have been caused initially by direct invasion of bone by epidermal squamous cell carcinoma and later by severe infection.

Carcinoma, Squamous Cell↗

PubMed1996

Effects of caffeine on event-related potentials: comparison of oddball with single-tone paradigms.

We investigated the acute effects of caffeine (500 mg) on event-related potentials (ERP) in 10 healthy subjects using standard oddball and single-tone paradigms. Event-related potentials were recorded before oral ingestion of caffeine or placebo and 30 min and 210 min after. The oddball paradigm, but not the single-tone paradigm, showed that the P300 amplitude and the area were significantly increased 30 min after ingestion of caffeine and significantly decreased 30 min after ingestion of placebo. The effects of caffeine disappeared at 210 min. Neither the P300 latency nor the reaction time changed significantly with the oddball paradigm. However, the reaction time was shortened 30 min after ingestion of caffeine with the single-tone paradigm. These findings suggest that the caffeine-induced increase in the P300 amplitude may have resulted from the increased allocation of attentional resources to the discriminating process which was not, however, accompanied by facilitation of the process and that caffeine may specifically stimulate the discriminating process involved in the oddball paradigm. In addition, the simple psychomotor performance of buttonpressing in response to a tone signal was accelerated by caffeine.

Caffeine↗

PubMed1996

Role of protein synthesis on ethanol regulation of adenylyl cyclase activity in wild-type S49 murine lymphoma cells.

Adenylyl cyclase activity was determined in membranes from wild-type S49 murine lymphoma cells that had been exposed to ethanol for 4 hr. Mn-, NaF-, and forskolin-stimulated adenylyl cyclase activities of cells-pretreated with cycloheximide, puromycin, or serum deprivation-were significantly decreased by treatment with 50 mM of ethanol. As demonstrated for Mn-stimulated activity, the decrease was dose-dependent on ethanol and was temporal; a normal activity recovered after 16-24 hr treatment, even in the presence of cycloheximide and ethanol. Studies with a cell-free membrane system of S49 cells revealed a similar activity decrease after treatment of the membranes with ethanol. In contrast, cells treated with 50 mM of ethanol in a regular culture condition showed no decrease in adenylyl cyclase activity over 24 hr. These results indicate that ethanol regulation of adenylyl cyclase activity in S49 cells depends on reduced or impaired protein synthesis.

Adenylyl Cyclase Inhibitors↗

PubMed1996

Molecular analysis of outer capsid glycoprotein (VP7) genes from two isolates of human group C rotavirus with different genome electropherotypes.

Nucleotide sequences for the VP7 gene of human group C rotavirus were determined for two strains isolated in Okayama, Japan, during a 1988-1990 epidemic. These isolates, OK118 and OK450, were selected as prototypes of two different electropherotypes, patterns I and II, respectively. The genes were identical in size (1,063 bp), and both contained singled open reading frames encoding 332 amino acids. The alignment of two sequences revealed 46 nucleotide substitutions, 11 of which were predicted to give amino acid changes. The deduced amino acid sequence of VP7 from OK118 was similar to published sequences of a Japanese isolate and three foreign isolates (more than 98.4% identity), whereas the VP7 sequence of OK450 revealed around 96% identity with these isolates and had nine unique amino acid substitutions. The VP7 genes of nine Okayama isolated were than analyzed by dot blot hybridization with the VP7 probes of OK118 and OK450. Under highly stringent conditions, the OK118 probe produced strong hybridization signals with the genes of five pattern I strains and one pattern II strain, while the OK450 probe strongly reacted only with those of three pattern II strains. Our results concluded that relative sequence diversity in the VP7 gene was observed between two different electropherotypes prevalent in a limited area.

Amino Acid Sequence↗

PubMed1996

Effect of Gamma Knife radiosurgery on acoustic neurinomas. Assessment by 99mTc-DTPA-human serum albumin- and 201TlCl-single photon emission computed tomography.

Single photon emission computed tomography (SPECT) was performed on 16 patients with acoustic neurinoma before and 1 and 2 years after Gamma Knife surgery. 201TICI-SPECT was used to determine tumor viability. Early and delayed images of 99mTc-DTPA-human serum albumin (99mTc-HSA-D)-SPECT were used to assess tumor vascularity and permeability, respectively. There was a statistically significant decrease in the 99mTc-HSA-D index of the early image at 1 year (p = 0.013) and at 2 years (p = 0.018) after Gamma Knife surgery. On the other hand, the 201Tl index and the 99mTc-HSA-D index of the delayed image were not significantly different from their pretreatment values. These observations demonstrate that a reduction in tumor vascularity without a decrease in tumor viability may be one of the effects of Gamma Knife surgery on acoustic neurinomas.

Adult↗

PubMed1996

Radiosurgery of brain metastases with the Gamma Knife.

A total of 130 patients with metastatic brain tumors were treated with the Gamma Knife; 85 had multiple lesions. The marginal dose was 14-30 Gy for the initial 20 cases during the first 6 months. Thereafter, we increased the marginal dose to between 25 and 30 Gy for the last 110 cases. The follow-up period ranged from 1 to 49 months (mean 9 months). The recurrence rate fell from 20% for the early low-dose cases to 4.6% for the later 110 higher-dose cases (p = 0.043). Transient neurological deterioration developed in 7 cases (5.4%), and permanent neurological deficits were recognized in a further 6 cases (4.6%). The relatively high prescription dose of 25-30 Gy at the margin of brain metastases treated with the Gamma Knife resulted in an acceptably high control rate with a low rate of complications.

Adult↗

PubMed1996

Estrogen regulates vascular endothelial growth/permeability factor expression in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors.

Vascular endothelial growth/permeability factor (VEG/PF) is expressed in some normal tissues and at high levels in a wide range of tumors. This growth factor is believed to be a key mediator of angiogenesis. Recent reports have shown that VEG/PF mRNA in the normal rat uterus is stimulated by estradiol (E2). In this study, we investigated the expression of VEG/PF in the mammary gland and 7,12-dimethylbenz(a)anthracene (DMBA)-induced, hormone-dependent mammary tumor of the rat model, and also whether VEG/PF is regulated by E2. VEG/PF mRNA from tumor extracts was amplified by RT-PCR with VEG/PF primers and generated two main products which corresponded in size to those expected for VEG/PF 164 and 120. In some cases, a third product corresponding in size to that expected for VEG/PF 188 was also generated. No such PCR products were generated from equal amount of RNA from normal mammary tissue, rat brain, or liver. Using immunocytochemistry, VEG/PF expression was detected in the epithelial cells of the tumors. We developed an ELISA assay to measure VEG/PF protein concentrations and found a 4-fold difference between normal mammary glands (1.3 +/- 0.11 ng/mg protein) and tumors (4.44 +/- 0.66) (P < 0.01). E2 treatment (5 microg/rat, s.c.) of rats 24 h after ovariectomy, greatly enhanced the expression of RT-PCR products in tumors within 2 h, which reached a maximum at 6-8 h but declined by 48 h. VEG/PF concentrations were also increased 8-12 h after E2 injection. When rats were given two injections of aromatase inhibitor 4-hydroxyandrostenedione (4-OHA 10 mg/rat s.c.) 24 h apart, to reduce estrogen concentrations, a low level of RT-PCR products was maintained for at least 96 h. After a single injection of 4-OHA, RT-PCR products remained low until 36 h when an increase occurred corresponding with a rise in plasma E2 levels. Injection of E2 2 h after 4-OHA treatment, caused a rise in RT-PCR products in 6-8 h. However, there was no significant change in VEG/PF concentrations. An increase in VEG/PF protein concentrations followed the increase in mRNA levels by 4-6 h. Thus, it appears that E2 causes a rapid induction of VEG/PF expression in mammary tumors that is similar to that observed in the normal uterus. These findings suggest that one mechanism by which estrogen acts as a mammary tumor promotor is by stimulating VEG/PF, leading to increased tumor angiogenesis and/or permeability of the microvessels to allow tumor cell migration.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1996

Effects of beraprost sodium and insulin on the electroretinogram, nerve conduction, and nerve blood flow in rats with streptozotocin-induced diabetes.

The effect of a prostacyclin analog, beraprost sodium, on the electroretinogram, motor nerve conduction velocity, and nerve blood flow was determined in rats with streptozotocin-induced diabetes and was compared with the effect of insulin. Beraprost sodium (0.01 mg x kg-1 x day-1 for 8 weeks) significantly shortened the peak latency of the electroretinogram b-wave, increased tail nerve conduction velocity, and increased sciatic nerve blood flow in diabetic rats (P < 0.0003, 0.0001, and 0.0001 vs. untreated diabetic rats, respectively). This was accompanied by a significant increase in the 6-keto-prostaglandin F1alpha content of the thoracic aorta and a marked increase in the cAMP content of the sciatic nerve. Beraprost sodium had no effect on the sorbitol and fructose contents of the sciatic nerve and retina, but insulin (8-10 U/day) significantly reduced both parameters. These findings suggest that beraprost sodium may be useful for prevention of vascular and neural dysfunction in the retina and peripheral nerve.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

An importance of carbohydrate ingestion for the expression of the effect of alpha-glucosidase inhibitor in NIDDM.

OBJECTIVE: To examine the usefulness of alpha-glucosidase inhibitors in glycemic control of patients with NIDDM. The involvement of carbohydrate ingestion in manifestation of the effects of alpha-glucosidase inhibitors was also investigated. RESEARCH DESIGN AND METHODS: A total of 41 patients hospitalized with NIDDM (22 patients receiving sulfonylurea and 19 receiving insulin therapy) were given alpha-glucosidase inhibitors during the period when their blood glucose levels were well controlled. They were followed for 3 weeks as inpatients and for an additional 6 months as outpatients. They were retrospectively divided into two groups according to the percentage of carbohydrates in all sources of calories during outpatient management: the < 50% group and the > 50% group. Between these two groups, we compared circadian variation in blood glucose levels, HbA1c, and urine C-peptide. RESULTS: Treatment with alpha-glucosidase inhibitors during the hospital stay markedly improved circadian variation in blood glucose levels and HbA1c and decreased urine C-peptide in both groups. While HbA1c returned to its pretreatment level at 6 months after the treatment in the < 50% group, HbA1c had further improved in the > 50% group at 6 months. CONCLUSIONS: alpha-Glucosidase inhibitors are useful for glycemic control in patients with NIDDM and the percentage of carbohydrate in all calorie sources is an important factor for the expression of their effects.

Biomarkers↗

PubMed1996

Absorption characteristics of dextrans with different molecular weights from the liver surface membrane in rats: implications for targeting to the liver.

We examined the importance of molecular weight on the absorption from the liver surface in rats using fluorescein isothiocyanate-dextrans (FDs) with molecular weights of 4,400 (FD-4), 9,300 (FD-10), 40,500 (FD-40) or 69,000 (FD-70). After application of FDs (5 mg) to the rat liver surface employing a cylindrical glass cell (i.d. 9 mm), each FD appeared gradually in the plasma, and the in vivo behavior was explained by two-compartment model with first-order absorption. The absorption ratios of FDs from the rat liver surface at 6 h, calculated from the amount recovered from the glass cell, decreased with an increase in the molecular weight (44.5% for FD-4, 29.3% for FD-10, 5.1% for FD-40 and 2.2% for FD-70). A linear relationship was observed between the absorption rate constant and the reciprocal value with square root of molecular weight of the model compounds. The limit of absorption from the rat liver surface was extrapolated to be at a molecular weight of 70,000. Furthermore, absorbed FDs were accumulated in the liver, as high liver/plasma concentration ratio as compared with that of i.v. administration. We clarified the molecular weight dependence of drug absorption from the liver surface in rats. Moreover, the liver surface application appeared to be a promising route with enhancing the efficacy of drug targeting to the liver.

Absorption↗