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Biomedical subjects

K Negishi

Publications and source records attributed to K Negishi.

265 records · Page 15Linked to original sources

Evidence that endogenous 6-(ARG or LYS)-opioid peptides can interact with kappa-receptors as agonists.

Evidence is provided for the abilities of endogenous 6-(Arg or Lys)-opioid peptides to interact with kappa-receptors as agonists. Dynorphin-(1-17) and -(1-8), alpha- and beta-neo-endorphin, [Met5]-enkephalin-Arg6-Phe7 and des acetyl salmon endorphin I significantly inhibited the electrically-evoked contractions of rabbit vas deferens which had been shown to contain kappa-receptors exclusively, indicating that endogenous 6-(Arg or Lys)-opioid peptides could act on kappa-receptors as agonists. Additionally, the inhibition of contractions of rabbit vas deferens by 6-(Arg or Lys)-opioid peptides was antagonized more effectively by Mr 2266 which had a high affinity to both mu- and kappa-receptors, than naloxone which had a high affinity only to mu-receptors. This also suggested that 6-(Arg or Lys)-opioid peptides acted as kappa-receptor agonists. The rank order of the inhibitory potency of 6-(Arg or Lys)-opioid peptides against contractions of rabbit vas deferens was as follows: dynorphin-(1-17) greater than alpha-neo-endorphin greater than beta-neo-endorphin .=. dynorphin-(1-8) greater than des acetyl salmon endorphin I greater than [Met5]-enkephalin-Arg6-Phe7. Since other endogenous opioid peptides such as [Met5]- and [Leu5]-enkephalin and beta-endorphin have been shown not to act on kappa-receptors as agonist, data in the present study suggest that endogenous opioid peptides can be classified into two groups in terms of an ability to interact with kappa-receptors as an agonist.

Animals↗

High glucose concentration suppresses mesangial laminin B2 gene expression.

To study the role of laminin in the rat mesangial cell attachment, cell adhesion to laminin-coated dishes was assayed by adding various amounts of a pentapeptide (YIGSR). YIGSR (20-100 micrograms/mL) inhibited the cell attachment to laminin-coated dishes. Mesangial laminin B2 messenger RNA (mRNA) levels were attenuated during exposure to 30 mM glucose or high osmolarity achieved by the addition of 25 mM choline chloride to 5 mM glucose (310 mOsm/kg H2O) for 3 hours. These results suggest that laminin, which may have a physiologic role in mesangial cell attachment, is produced in mesangial cells, and that the decrease of laminin B2 mRNA during hyperglycemia or exposure to high osmolarity may have some pathophysiologic significance in the development of diabetic nephropathy.

Amino Acid Sequence↗

Serum or urinary concentration of type IV collagen in diabetics.

Concentrations of serum or urinary type IV collagen, determined by sandwich enzyme immunoassay, were significantly elevated in diabetics compared to controls (P less than .01). Serum or urinary levels of type IV collagen were significantly increased in patients with microangiopathy compared to those without microvascular disease (P less than .05). Serum type IV collagen levels were also augmented in diabetics who showed an increased albumin index for 1 year. Serum levels of type IV collagen were not affected by any conditions of metabolic control. The measurement of serum or urinary type IV collagen may be a useful indicator for monitoring the development of diabetic microangiopathy, especially in early diabetic nephropathy.

Biomarkers↗

Glucose-induced production of type IV collagen and laminin P1 from cultured human umbilical vein endothelial cells.

To study the effect of high glucose on the production of type IV collagen and laminin P1 from the cultured human umbilical vein endothelial cells (HUVEC), we measured type N collagen and laminin P1 from HUVEC that were cultured under different conditions. The concentrations of type IV collagen in the cultured medium for high glucose (30 mM D-glucose) were significantly higher than those for low glucose (5.6 mM D-glucose), L-glucose (30 mM), or mannitol (30 mM). The increase of type IV collagen was dependent on the glucose concentration in the medium. The contents of type IV collagen in the cultured cells were also increased in high-glucose incubation compared with low glucose or L-glucose incubation. In contrast, the levels of laminin P1 in the medium cultured with high glucose were similar to those with low glucose or L-glucose. These results suggest that the increased production of type IV collagen may contribute to the thickening of basement membranes and may be linked to the development of diabetic nephropathy.

Cell Division↗

The relationship between early diabetic nephropathy and control of plasma glucose in non-insulin-dependent diabetes mellitus. The effect of glycemic control on the development and progression of diabetic nephropathy in an 8-year follow-up study.

To clarify the relationship between early diabetic nephropathy and the glycemic control in non-insulin-dependent diabetes mellitus (NIDDM) without hypertension, excretion of urinary albumin was studied retrospectively for 8 years. The patients with early diabetic nephropathy were divided into two groups according to the initial urinary albumin index (UAI: mg/g.creatinine), namely, a normoalbuminuric (less than 15 mg/g.creatinine) and a microalbuminuric group (15 < or = UAI < 200 mg/g.creatinine). Comparisons of changes in UAI were made between good (HbA1 < 9.0% and fasting plasma glucose (FPG) < 140 mg/100 mL throughout the observation period) and poor glycemic control groups after 4 and 8 years. In the patients with normoalbuminuria at the initial determination, five of 11 patients (45.5%) with good glycemic control and 14 of 22 patients (63.6%) with poor glycemic control became microalbuminuric after 8 years, respectively (p < 0.05). In the microalbuminuric patients, five of ten patients (50%) with poor glycemic control became macroalbuminuric (UAI > or = 200 mg/g.creatinine), although only one case worsened of five patients with good glycemic control (p < 0.05). In conclusion, the development or progression of early diabetic nephropathy in NIDDM was significantly inhibited by good glycemic control (FPG < 140 mg/100 mL and HbA1 < 9.0%), independent of hypertension, and probably irrespective of the mode of therapeutic intervention.

Albuminuria↗

IgG subclasses of islet cell surface antibodies and their cytotoxic activity against pancreatic islet cells.

IgG subclasses of islet cell surface antibodies (ICSA) and their cytotoxic activities against pancreatic islet cells in the presence of complements were simultaneously investigated in ICSA-positive patients with insulin-dependent diabetes mellitus (n = 15). ICSA (IgG class) and ICSA-IgG subclasses were determined by flow cytometry using a fluorescence-activated cell sorter (FACS). Complement-dependent antibody-mediated cytotoxicity (CAMC) was measured by release of 51Cr from target cells. For these assays, rat insulinoma (RINr) cells were used as antigenic or target cells. Sera from 11 out of 15 patients who were positive for ICSA possessed at least one positive ICSA-IgG subclass, though these sera did not always exert positive CAMC activities. When the relationship between ICSA-IgG subclasses and CAMC was tested by chi-square analysis, a significant relationship (P less than 0.01) was observed between ICSA-IgG3 and CAMC. In sera from the other four patients, not any positive ICSA-IgG subclass or CAMC activity was found. The data suggest that (1) ICSA (IgG class) found in diabetics are not always cytotoxic to pancreatic islet cells, (2) the IgG subclass of ICSA varies with the patients, and (3) ICSA-IgG3 have a significantly higher association with CAMC to pancreatic islet cells. Thus, ICSA (IgG class) might not always be responsible for the impairment of pancreatic islet cells, at least in part, because of the heterogenous ICSA-IgG subclass.

Adolescent↗

Clinical evaluation of a five-zone refractive multifocal intraocular lens.

PURPOSE: To evaluate the clinical performance of a five-zone refractive multifocal intraocular lens (AMO, model MPC-25NB, Array). METHODS: We performed a retrospective clinical trial of 31 cataract patients (mean age 64.3 years). The parameters studied were intraoperative and postoperative complications, distance and near visual acuity, spectacle use, decreased number of corneal endothelial cells, contrast sensitivity, percentage of glare disability, near binocular vision, and depth of focus. RESULTS: Intraoperatively, iris damage occurred in two eyes (4.2%), vitreous loss in one eye (2.1%), and consecutive rupture of Zinn's zonule and vitreous in one eye (2.1%). Postoperatively, posterior capsule opacification was observed in two eyes (4.2%), temporary intraocular pressure increase in one eye (2.1%), and cystoid macular edema in one eye (2.1%). Uncorrected distance visual acuity of 20/40 or better was achieved by 34 of 37 eyes (91.9%) with less than 1.5 diopters of preoperative keratometric astigmatism; best corrected distance acuity of 20/20 or better was achieved by 41 of 45 eyes (91.1%). Near visual acuity with distance correction of 20/40 or better was achieved by 29 of 43 eyes (67.4%). These data were compared retrospectively with data from control patients who received monofocal lenses, and no significant differences in the decreased number of corneal endothelial cells were found. Mean contrast sensitivities were within normal range for all spatial frequencies. Percentage of glare disability and near binocular vision were within normal limits. CONCLUSIONS: Eyes implanted with the five-zone refractive multifocal lens showed better near visual acuity than control eyes and compared favorably in other aspects of visual function, indicating that these lenses are effective and safe.

Adult↗

Defining a neural network controller structure for a rubbertuator robot.

Rubbertuator (Rubber-Actuator) robot arm is a pneumatic robot, unique with its lightweight, high power, compliant and spark free nature. Compressibility of air in the actuator tubes and the elastic nature of the rubber, however, are the two major sources of increased non-linearity and complexity in motion control. Soft computing, exploiting the tolerance of uncertainty and vagueness in cognitive reasoning has been offering easy to handle, robust, and low-priced solutions to several non-linear industrial applications. Nonetheless, the black-box approach in these systems results in application specific architectures with some important design parameters left for fine tuning (i.e. number of nodes in a neural network). In this study we propose a more systematic method in defining the structure of a soft computing technique, namely the backpropagation neural network, when used as a controller for rubbertuator robot systems. The structure of the neural network is based on the physical model of the robot, while the neural network itself is trained to learn the trajectory independent parameters of the model that are essential for defining the robot dynamics. The proposed system performance was compared with a well-tuned PID controller and shown to be more accurate in trajectory control for rubbertuator robots.

Elasticity↗

The occurrence of dopaminergic interplexiform cells correlates with the presence of cones in the retinae of fish.

Using light-microscopic immunocytochemistry against tyrosine hydroxylase, we have investigated the morphology of dopaminergic cells in 23 species of fishes representing various systematic classes and subclasses and which live in very different habitats. We have, for the first time, observed teleosts with dopaminergic amacrine cells. Thus, in both bony and cartilaginous fishes, dopaminergic cells are differentiated as interplexiform and amacrine cells. The differentiation of dopaminergic cells into amacrine or interplexiform cells in fishes correlates with the absence or presence of cones. In pure-rod retinae, they occur as amacrine cells, and in mixed rod/cone retinae, they occur as interplexiform cells. We conclude therefore that the differentiation of retinal dopaminergic cells in fish does not depend on the evolutionary or systematic classification of a given species. Rather, it is correlated with the occurrence of rods and/or cones, and thus linked more closely to the habitat. We argue that, in fish, the presence of cones and cone-specific horizontal cells may be responsible for inducing dopaminergic cells to differentiate as interplexiform cells. Possible functions of dopamine in all-rod retinae, which may not require adaptation, may include neuromodulation in the inner plexiform layer for the sensitization of the rod pathway, the shaping of biological rhythms, and the control of eye growth.

Animals↗

GABA sensitivity of spectrally classified horizontal cells in goldfish retina.

We studied the GABA sensitivity of horizontal cells in the isolated goldfish retina. After the glutamatergic input to the horizontal cells was blocked with DNQX, GABA depolarized the monophasic and biphasic horizontal cells. The pharmacology of these GABA-induced depolarizations was tested with the GABA receptor antagonists bicuculline-methiodide and picrotoxin, the GABA transporter agonist nipecotic acid, and the GABA transporter antagonist SKF 89976-A. The GABA-induced responses of monophasic horizontal cells consisted of two components; one with characteristics of GABA-gated chloride channels, and one with characteristics of GABA transporters. In biphasic horizontal cells, we only found evidence for GABA-gated chloride channels. The results show that monophasic horizontal cells in goldfish contain the two components of a positive feedback loop (GABA transporters and GABA-gated chloride channels), as described in salamander. Furthermore, our results indicate that the monophasic horizontal cells may project directly to the biphasic horizontal cells, via an excitatory GABAergic pathway. We propose that the function of these GABAergic systems in horizontal cells is to abolish cone dominance in bipolar cells surround in the dark-adapted retina.

6-Cyano-7-nitroquinoxaline-2,3-dione↗