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Biomedical subjects

J Nakamura

Publications and source records attributed to J Nakamura.

At least 217 records · Page 12Linked to original sources
PubMed1997

Effect of an aldose reductase inhibitor on abnormalities of electroretinogram and vascular factors in diabetic rats.

The effect of an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl] acetic acid (TAT), on the electroretinogram was determined in rats with streptozotocin-induced diabetes. Laboratory chow containing 0.05% TAT was given to rats for 2 months, while other diabetic rats were untreated. Groups of TAT-treated and untreated normal rats were also studied. Treatment with TAT produced significant improvement of the electroretinogram. TAT shortened the peak latencies of the b-wave oscillatory potentials, which were significantly prolonged in untreated diabetic rats (P < 0.0001 vs. untreated normal rats). This was accompanied by a significant decrease in the retinal sorbitol and fructose concentrations (by 46.5% and 25.7%, respectively). TAT treatment of diabetic rats also markedly reduced ADP-induced platelet aggregation and significantly increased the red blood cell 2,3-diphosphoglycerate level, accompanied by a marked reduction in sorbitol and fructose concentrations of platelet and red blood cells. There were significant correlations between the summed b-wave peak latencies and platelet aggregation or the 2,3-diphosphoglycerate level in diabetic rats. These findings suggest that an aldose reductase inhibitor, TAT, has therapeutic value for diabetic retinopathy.

2,3-Diphosphoglycerate↗
PubMed1997

Diabetic neuropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats: effect of an aldose reductase inhibitor, TAT.

In an animal model of human non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed with sucrose for 8 weeks to obtain severe hyperglycemia. The effects of sucrose administration on peripheral nerve functions, motor nerve conduction velocity (MNCV) and coefficient of variance of R-R interval (CVR-R), were investigated with concomitant measuring of sciatic nerve blood flow (SNBF), ADP-induced platelet aggregation and polyol content in the sciatic nerves. The effects of an aldose reductase inhibitor, TAT, on these parameters were also studied. Administration of sucrose to OLETF rats caused significant body weight reduction and remarkable hyperglycemia. Sucrose-fed OLETF rats demonstrated significantly delayed MNCV, decreased CVR-R, reduced SNBF and increased platelet aggregation activity to ADP. Sorbitol and fructose accumulation, and myo-inositol depletion in sciatic nerves were observed only in sucrose-fed OLETF rats. These abnormalities were all ameliorated by the treatment with TAT. These observations suggest that the sucrose-fed OLETF rat is a useful animal model for studying the pathogenesis of diabetic neuropathy in human NIDDM, and that an aldose reductase inhibitor is a useful therapeutic agent for the treatment of diabetic neuropathy.

Aldehyde Reductase↗
PubMed1997

Quantification of regional cerebral blood flow and vascular reserve in childhood moyamoya disease using [123I]IMP-ARG method.

Both regional cerebral blood flow (rCBF) and regional vascular reserve (rVR) in ten childhood Moyamoya disease were quantified pre- and post-operatively by autoradiographic processing using single photon emission computed tomography (SPECT) and N-isopropyl-rho-iodoamphetamine (IMP) (IMP-ARG method) to estimate hemodynamic effectiveness of surgical revascularization. Before surgery, in two patients, rCBF was reduced in the whole territories and loss of rVR in the anterior circulation was observed; +4.3% in the anterior cerebral artery (ACA), -3.0% in the middle cerebral artery (MCA) and +17.5% in posterior cerebral artery (PCA) territories. After surgery, in eight patients without transient ischemic attack (TIA) episodes, rCBF at rest was maintained around subnormal level in the whole territories, and mean rVR was up to +11.9, +17.3 and +28.3% in ACA, MCA and PCA territories, respectively. However, rVR in the anterior circulation was significantly reduced in comparison with rVR in the posterior circulation. Quantification of both resting rCBF and rVR using IMP-ARG method could provide reliable information concerning on surgical indication and its effectiveness in childhood Moyamoya disease.

Adolescent↗
PubMed1997

The usefulness of anti-fucosylated antigen antibody YB-2 for diagnosis of hepatocellular carcinoma.

Levels of fucosylated antigens in sera from patients with liver diseases were examined by a newly developed sandwich-type enzyme immuno assay with the aid of anti-fucosylated antigen antibody, YB-2 which reacts simultaneously with Y, Leb and H type 2 antigens. When the cut-off value was set arbitrarily at mean +3 SD values of normal, 30 (69.8%) of the 43 patients with HCC, 14 (53.8%) of the 26 patients with liver cirrhosis (LC) and 24 (45.3%) of the 53 patients with chronic hepatitis (CH) were found to be positive, whereas all of the 30 samples from healthy controls were negative. The levels of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in HCC were not correlated with those of YB-2 antigens. The positive rates of the combination YB-2 and AFP assay and YB-2 and PIVKA-II assay in HCC were significantly higher (83.7 and 86.0%, respectively) than that of the AFP and PIVKA-II combination (65.1%) which had been reported to be the best combination up to this time.

Adult↗
PubMed1997

Temperature sensitivity of proteoliposomes reconstituted from a mixture of scallop and rabbit sarcoplasmic reticulum Ca2+-ATPases.

We reconstituted proteoliposomes by mixing scallop and rabbit sarcoplasmic reticulum, SR, at different protein weight ratios, and investigated the effects of temperature on their Ca2+-transport activity. When proteoliposomes containing scallop and rabbit SR at a protein ratio of 1:1 were pre-incubated in the presence of Ca2+ at 39 degrees C for 10 min, the Ca2+-transport activity was almost completely lost, whereas the activity of proteoliposomes containing rabbit SR alone decreased only slightly. Essentially the same results were obtained for proteoliposomes reconstituted with Ca2+-ATPases partially purified from scallop and rabbit SR. The susceptibility of the reconstituted proteoliposomes to heat inactivation increased with an increase in the protein weight ratio of scallop to rabbit SR, the maximum being approached at a ratio higher than 1. When the scallop SR was thermally treated before reconstitution, the resulting vesicles showed as high Ca2+-transport activity as that of control vesicles reconstituted from rabbit SR alone. The former vesicles were not inactivated on further treatment at high temperature. In contrast, when the scallop SR was heated in EGTA before reconstitution of vesicles with rabbit SR, the Ca2+-transport activity of the vesicles was strongly inhibited by subsequent treatment at high temperature in the presence of Ca2+. These results can be easily explained if we assume that Ca2+ transport by the reconstituted vesicles can be catalyzed through a dimeric interaction between the scallop and rabbit Ca2+-ATPases in the membrane. Pre-incubation of these vesicles at 39 degrees C for 10 min in the presence of Ca2+ may destroy the dimeric interaction due to denaturation of the scallop Ca2+-ATPase.

Animals↗
PubMed1997

Ocular surface disorders in the critically ill.

Abnormalities of the cornea and conjunctiva occur in association with neurological diseases, nocturnal lagophthalmos, coma, infection, and mechanical ventilation. We investigated the incidence and causes of ocular surface disorders in critically ill patients. In a retrospective study, the presence of conjunctivitis and corneal erosion was determined by reviewing the medical charts of 143 mechanically ventilated patients (intensive care unit [ICU] stay > or =7 days). In the subsequent prospective study, 15 patients who had sedatives or muscle relaxants administered continuously for more than 48 h in the ICU were investigated. Corneal erosion was examined using a slit lamp once a day. Ocular surface disorder was found in 28 of the 143 patients (20%) whose ICU stay exceeded 7 days. The incidence increased with continuous sedation (35% vs 15%). The incidence also increased with continuous neuromuscular blockade (39% vs 11%). In the prospective study, nine patients (60%) developed corneal erosion. A patient's inability to fully close his or her eyes increased the incidence (P < 0.01) of corneal erosion. Protective eyelid taping was effective in preventing and treating the corneal erosion. In conclusion, the critically ill often develop ocular surface disorders, especially when sedated and immobilized. A close relationship was observed between these conditions and the inability to close one's eyes.

Adolescent↗
PubMed1997

Does plasma free-3-methoxy-4-hydroxyphenyl(ethylene)glycol increase in the delirious state? A comparison of the effects of mianserin and haloperidol on delirium.

Sixty-six patients (47 men, 19 women, mean age 65 years) with delirium were treated with mianserin (10-60 mg/day) or haloperidol (2-6 mg/day) at Kurume University Hospital. The clinical effects of these drugs were compared before and after treatment using the Delirium Rating Scale. At the same time, blood was sampled to analyse plasma mianserin, free-3-methoxy-4-hydroxyphenyl(ethylene)glycol (MHPG) and homovanillic acid concentrations. Marked improvement after 1 week was observed in 69.4% of patients undergoing mianserin treatment, and in 70.6% of those receiving haloperidol. A statistically significant difference in the clinical effects of these drugs was not observed. Although improvement in the delirious state and a decrease in the plasma free-MHPG concentration were observed after drug administration, the plasma free-homovanillic acid concentration showed no significant change. The higher plasma free-MHPG concentration in the delirious state suggests the existence of a preparatory state whereby noradrenaline metabolism is involved in the appearance of the abnormal behaviour associated with delirium. These data suggest that free-MHPG concentrations could potentially be used as a predictor of delirium.

Aged↗
PubMed1997

Transmission of human herpesvirus 7 through multigenerational families in the same household.

BACKGROUND: Human herpesvirus 7 (HHV-7) closely resembles HHV-6 and to a lesser degree cytomegalovirus. HHV-7 infection is usually acquired during early childhood. Primary infection can cause a roseola-like illness but in most cases it is only mildly symptomatic. The majority of adults are seropositive and in contrast to HHV-6 and cytomegalovirus infection, they continue to secrete the virus in their saliva for many years. The mode of intrafamilial transmission of this virus is not well-understood. METHODS: Saliva samples for virus isolation and DNA restriction analysis were obtained from all 47 members of 6 Japanese families, including 4 families with 3 generations living in the same household. RESULTS: HHV-7 was isolated from 43 of 47 saliva samples collected from children and adult members of the 6 families (91.5%). In one family the restriction patterns of the maternal grandmother, the mother and the children were similar, and the patterns of the paternal grandmother and the father were similar. In another family the patterns of the father and 5 of 6 children were similar, and those of the mother and the other child were similar. Altogether similar HHV-7 restriction profiles with his or her mother were found in 48% of offspring, and similar profiles with his or her father were found in 28% of offspring. CONCLUSIONS: The results strongly suggested horizontal transmission of HHV-7 from grandparents to parents to children through close contact within a household. Either parent could transmit HHV-7 to the children.

Adolescent↗
PubMed1997

In vitro selection of variants of herpes simplex virus type 1 which differ in cytopathic changes.

To analyze the mechanisms for in vitro emergence of the syncytial variants of herpes simplex virus type 1 (HSV-1), several cell lines were infected with a mixture of equal amounts of two HSV-1 variants, one syncytial and the other non-syncytial, and changes in their relative abundance were monitored during passage. With a combination of two variants of the Miyama strain of HSV-1, the syncytial variant became dominant during passage in Vero, RK-13 and FL cells. On the other hand, the ratios of the two variants remained around 1:1 during the passage in HEp-2, MGC and HEL cells. In another set of variants of the SKO strain of HSV-1, the outcomes were different from those of the Miyama strain in the FL, MGC and HEp-2 cells. The ratios of the two variants remained around 1:1 during passage in FL cells, while the non-syncytial variant became dominant during passage in MGC and HEp-2 cells. In addition, we examined the effects of a complement and interferon-beta (IFN-beta) on the outcome of the selection. As a result, the complement slowed the selection of a syncytial variant, whereas IFN-beta facilitated it.

Cell Line↗
PubMed1997

Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin administration in F344 rats.

The influence of bovine lactoferrin (bLF) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). Following three weekly injections of AOM, the animals received 2 or 0.2% bLF for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with both doses. Thus, the incidences of adenocarcinomas in the groups receiving 2% and 0.2% bLF were 15% and 25%, respectively, in contrast to the 57.5% control value (P < 0.01 and P < 0.05, respectively). The results indicate that bLF might find application for chemoprevention of colon cancer.

Adenocarcinoma↗
PubMed1997

Effect of application volume and area on the absorption of phenol red, as a model drug, from the liver surface in rats.

To determine the influence of the method of administration of a pharmaceutical formulation we have examined the importance of application volume and area in the absorption of phenol red, as a model drug, from the rat-liver surface. When 1 mg phenol red was applied to the rat-liver surface, in-vivo, in three volumes (0.1, 0.2 or 0.334 mL) using a cylindrical glass cell (i.d. 9 mm), the shape of the plasma concentration profile differed greatly, particularly the maximum concentration. These patterns were well fitted by a two-compartment model with first-order absorption, and the absorption-rate constant Ka obtained was inversely proportional to the application volume. The absorption ratio and biliary recovery of phenol red after 6 h increased with glass cell area (i.d. 6, 9 or 14 mm; area 0.28, 0.64 or 1.54 cm2). Furthermore, the permeability coefficient Papp derived from Ka did not depend on application area, indicating no difference in the absorption characteristics of the liver surface. This also implies transport of the drug by passive diffusion from the liver surface. After intraperitoneal administration to the rat-liver surface for clinical application, increasing the application volume resulted in the delayed disappearance of phenol red from the plasma. However, the difference was not as marked as that obtained by use of the glass cell. The assumption that the effective area relating to the absorption changed with the application volume enabled us to estimate Papp. Consequently, we speculate that absorbability can be estimated precisely by consideration of application volume and area.

Adsorption↗
PubMed1997

Ocular membrane permeability of hydrophilic drugs for ocular peptide delivery.

The purpose of this study is to investigate the ocular membrane permeability and the permeation mechanism of hydrophilic drugs such as thyrotropin-releasing hormone (TRH), p-nitrophenyl beta-cellopentaoside (PNP) and luteinizing hormone-releasing hormone (LHRH). The penetration of hydrophilic drugs was measured across the isolated corneal and conjunctival membranes of albino rabbits using a two-chamber diffusion glass cell. The corneal permeabilities of hydrophilic drugs were much lower than those of beta blockers reported previously. The corneal penetration of TRH was the highest among the hydrophilic drugs studied. Scraping the corneal epithelium increased the penetration of hydrophilic drugs. Conjunctival membranes showed higher permeability to hydrophilic drugs compared with corneal membranes. The permeability of drugs was also analysed by Fick's equation. The partition parameter and diffusion parameter of TRH, PNP and LHRH in the cornea were lower than those in scraped cornea and conjunctiva. In addition to the data of fluorescein isothiocyanate-dextran reported previously, the permeability coefficient of hydrophilic drugs through the cornea, scraped cornea and conjunctiva correlated with molecular weight of the drugs. The diffusion parameters of hydrophilic drugs decreased with an increase of molecular weight for all ocular membranes. The extent of dependency of partition parameters on the molecular weights of drugs varied according to the ocular membrane. These results indicate that ocular membranes are sufficiently different in permeation character and mechanism to control the extent and pathway for ocular absorption of hydrophilic drugs.

Animals↗
PubMed1997

In-situ ocular absorption of ophthalmic beta-blockers through ocular membranes in albino rabbits.

Ocular membranes have been characterized by in-situ absorption of the ophthalmic beta-blockers carteolol (hydrophilic) and timolol and befunolol (lipophilic) using a cylindrical cell. After introduction of drug solution into the cell on the cornea, sclera (bulbar conjunctival and scleral layer) or palpebral conjunctiva, the disappearance of the drug from the cell was determined as in-situ absorption. The ophthalmic drugs disappeared from the conjunctival and scleral membranes although disappearance from the cornea was hardly observed. The conjunctival membrane showed the highest permeability. Lipophilic drugs were more permeable than hydrophilic. In-situ apparent permeability coefficients of the ophthalmic drugs through the conjunctiva and sclera correlated with the lipophilicity of drugs. A high drug concentration in the aqueous humor was observed after corneal application. There is a relationship between concentration in the aqueous humor was observed after corneal application. There is a relationship between concentrations of drugs in the aqueous humor and previously reported in-vitro apparent permeability coefficients of the drugs in the cornea. This in-situ method using a cylindrical cell is a useful method of investigating the ocular absorption of ophthalmic drugs.

Absorption↗
PubMed1997

Electroretinogram in sucrose-fed diabetic rats treated with an aldose reductase inhibitor or an anticoagulant.

To investigate the role of increased polyol pathway activity and hemodynamic deficits in the pathogenesis of diabetic retinopathy in non-insulin-dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human NIDDM, were given water with or without 30% sucrose and some of them were fed laboratory chow containing 0.03% cilostazol, an anticoagulant, or 0.05% [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (TAT), an aldose reductase inhibitor, for 8 wk. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. The peak latencies of oscillatory potentials of the electroretinogram in sucrose-fed OLETF rats were significantly prolonged compared with those in OLETF rats without sucrose feeding and LETO rats. There was a marked increase in platelet aggregability and a significant decrease in erythrocyte 2,3-diphosphoglycerate in sucrose-fed OLETF rats. Cilostazol significantly improved these parameters without changes in retinal levels of sorbitol and fructose. TAT, however, ameliorated all of these parameters. These findings confirm that the sucrose-fed OLETF rat is a useful animal model of retinopathy in human NIDDM and suggest that cilostazol improved diabetic retinopathy by modifying vascular factors, not by altering polyol pathway activity.

2,3-Diphosphoglycerate↗
PubMed1997

Effects of irradiation of an erbium:YAG laser on root surfaces.

The application of erbium:YAG laser (Er:YAG) irradiation has been investigated for periodontal therapy. The purpose of this study was to evaluate the effects of Er:YAG laser irradiation on root surfaces using a scanning electron microscope (SEM) and to determine the laser's ability to remove lipopolysaccharides (LPS). Infrared spectrophotometry was used to investigate the effects of the laser on LPS applied to root dentin pellets. Premolars extracted for orthodontic reasons were prepared for this study. The crowns were resected below the cemento-enamel junction, longitudinally sectioned, and the contents of the pulp chamber were removed. Then 15 root tips (5 x 5 x 1 mm) were classified into 3 groups of 5 each as follows: group 1, tips without any treatment; group 2, planed tips with the cement layers left untouched; and group 3, planed until the dentin surface was disclosed. The center of each specimen was used as the experimental irradiated area and the peripheral area served as a control. The quantity of vapor delivered by Er:YAG laser was highly increased, and the irradiated areas displayed little morphogenetic changes. The lyophilized sample LPS 0111 B4 from E. coli was then mixed with potassium bromide and pressed into a tablet, which was examined at 4,000-650 Kayser. The lyophilized LPS had a peak at 2.94 microns. LPS on the root dentin pellets was cleared away as much as possible by 150 washings in pyrogen-free water using an ultrasonic cleaner. Five microliters of 24 EU LPS solution was dropped on the root dentin pellets, which were then irradiated by the Er:YAG laser, and washed using the ultrasonic cleaner in pyrogen-free water. The amount of the extracted LPS solution was determined by spectrophotometer at 405 nm. The Er:YAG laser could remove 83.1% of the LPS. This study suggests that Er:YAG laser irradiation might be useful for root conditioning in periodontal therapy. However, clinical testing is necessary to establish what, if any, utility the Er:YAG laser has as a part of periodontal therapy.

Aluminum Silicates↗
PubMed1997

Early effects of gamma knife radiosurgery on brain metastases: assessment by 201TlCl SPECT and 99mTc-DTPA-human serum albumin SPECT.

Thallium-201 chloride (201TlCl) single photon emission computed tomography (SPECT) was used to determine tumor viability, and the early and delayed images of technetium-99m-diethylenetriaminepenta-acetic acid-human serum albumin (99mTc-HSA-D) SPECT were used to assess tumor vascularity and permeability, respectively, in 17 patients with 18 brain metastases. SPECT was performed before, 1 week after, and 1 month after radiosurgery. The ratios of 201Tl and 99mTc-HSA-D uptake in a tumor were expressed as a ratio to uptake in the corresponding normal contralateral areas (uptake index). Magnetic resonance imaging with gadolinium was used to determine tumor volume. 201Tl index decreased significantly 1 week (p < 0.05) and 1 month (p < 0.005) after radiosurgery. In contrast, 99mTc-HSA-D indices of early and delayed images obtained at 1 week after radiosurgery were not significantly different from the pretreatment values. However, both were significantly low (p < 0.05) 1 month after radiosurgery. No change in tumor volume was detected 1 week following radiosurgery, but there was a significant decrease (p < 0.005) after 1 month. The reduction in tumor viability that occurs before the appearance of evidence of tumor shrinkage represents the early effect of radiosurgery on brain metastases. Reduction in tumor size, vascularity, and permeability occur subsequently.

Adult↗
PubMed1997

Effects of glycemic control on plasma 3-deoxyglucosone levels in NIDDM patients.

OBJECTIVE: To clarify the effects of glycemic control on the level of 3-deoxyglucosone (3-DG), a reactive dicarbonyl compound, in plasma from diabetic patients. RESEARCH DESIGN AND METHODS: Fasting plasma samples were collected from 15 healthy volunteers and 27 patients with NIDDM. Samples were collected from six poorly controlled patients before and after improved glycemic control for at least 2 months. Plasma 3-DG was determined by high-performance liquid chromatography (HPLC) as a 2,3-diaminonaphthalene derivative. We observed the relationship of 3-DG levels with plasma glucose or HbA1c levels and examined changes in 3-DG levels after glycemic control in the six patients. RESULTS: Plasma 3-DG was significantly more increased in diabetic patients than in nondiabetic control subjects (31.8 +/- 11.3 vs. 12.8 +/- 5.2 ng/ml, means +/- SD, P < 0.001), but there was an approximately threefold difference in 3-DG levels among diabetic patients. 3-DG levels were well correlated with plasma glucose (r = 0.56, P < 0.005) and HbA1c levels (r = 0.74, P < 0.001) in diabetic patients. The improvement of hyperglycemia in six patients resulted in a significant decrease in 3-DG (35.2 +/- 13.2 vs. 21.3 +/- 3.4 ng/ml, P < 0.05). CONCLUSIONS: The results indicate that the plasma glucose level is a predominant determinant of the plasma 3-DG level in diabetic patients and good glycemic control would be important to reduce this reactive metabolite.

Adult↗