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Biomedical subjects

N Hori

Publications and source records attributed to N Hori.

At least 55 records · Page 3Linked to original sources
PubMed1997

Role of calcitonin gene-related peptide in the vascular system on the development of the hyperdynamic circulation in conscious cirrhotic rats.

BACKGROUND/AIMS: Calcitonin gene-related peptide (CGRP), a potent vasodilator; plays an important role in modulating vascular tone, acting as a noncholinergic nonadrenergic neurotransmitter. The aim of this study was to assess the role of CGRP, present in the vascular system, in the development of the hyperdynamic circulation observed in liver cirrhosis. METHODS: Two doses of human alpha-CGRP [8-37], a specific antagonist of CGRP, were administered to cirrhotic and controls rats. Hemodynamics were evaluated using radioactive microspheres in conscious animals. To investigate the arterial depressor effect of exogenous CGRP, we constructed a dose-response curve for mean arterial pressure in cirrhotic and control rats by administering human alpha-CGRP. RESULTS: The administration of high-dose human alpha-CGRP [8-37] (300 nmol.kg body weight-1.min-1) significantly increased both the mean arterial pressure (21 +/- 2 vs. 13 +/- 1%, p < 0.01) and total vascular resistance (76 +/- 5 vs. 54 +/- 5%, p < 0.01) in cirrhotic rats, compared to control rats. The splanchnic hemodynamic effects induced by human alpha-CGRP [8-37] were a significant decrease in percent change of portal venous inflow -42 +/- 3 vs. -33 +/- 3%, p < 0.05) and a significant increase in percent change of splanchnic arterial resistance (110 +/- 9 vs. 76 +/- 5%, p < 0.01) in cirrhotic rats, compared to control rats. Low-dose human alpha-CGRP [8-37] (60 nmol.kg body weight-1. min-1) caused similar hemodynamic changes, but the degree of change was much less than for the high-dose administration. The vascular response to human alpha-CGRP was significantly reduced in cirrhotic rats as compared to controls (ANOVA, p < 0.01). Plasma concentrations of CGRP were significantly elevated in cirrhotic rats. CONCLUSIONS: CGRP in the vascular system was involved in the modulation of vasodilatation in rats with liver cirrhosis, as demonstrated by the administration of a selective CGRP antagonist and exogenous CGRP.

Animals↗
PubMed1997

Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals.

1. Carnosine, anserine, and homocarnosine are endogenous dipeptides concentrated in brain and muscle whose biological functions remain in doubt. 2. We have tested the hypothesis that these compounds function as endogenous protective substances against molecular and cellular damage from free radicals, using two isolated enzyme systems and two models of ischemic brain injury. Carnosine and homocarnosine are both effective in activating brain Na, K-ATPase measured under optimal conditions and in reducing the loss of its activity caused by incubation with hydrogen peroxide. 3. In contrast, all three endogenous dipeptides cause a reduction in the activity of brain tyrosine hydroxylase, an enzyme activated by free radicals. In hippocampal brain slices subjected to ischemia, carnosine increased the time to loss of excitability. 4. In in vivo experiments on rats under experimental hypobaric hypoxia, carnosine increased the time to loss of ability to stand and breath and decreased the time to recovery. 5. These actions are explicable by effects of carnosine and related compounds which neutralize free radicals, particularly hydroxyl radicals. In all experiments the effective concentration of carnosine was comparable to or lower than those found in brain. These observations provide further support for the conclusion that protection against free radical damage is a major role of carnosine, anserine, and homocarnosine.

Animals↗
PubMed1997

Inverted repeats in the TATA-less promoter of the rat catalase gene.

The rat catalase gene promoter lacks a TATA box, and has eight initiation sites of transcription as well as several GT and CCAAT boxes. To elucidate the mechanism of transcription in this TATA-less promoter, we analyzed nuclear factors binding to this regulatory region of the catalase gene. Functional analysis of the promoter region revealed that a pair of inverted repeat motifs located on both sides of the transcription initiation sites played an important role in the gene expression. The core sequence of this element is GYCMGGCCCKCTCYKG (M=A/C, K=G/T, Y=T/C), and four species of complex were observed to bind to this sequence. Furthermore, this element in the chimeric promoter negatively interacted with the initiator element of the terminal deoxynucleotidyl transferase gene. These results suggested that the rat catalase gene is regulated by a novel mechanism involving the inverted repeated structure of the promoter and characteristic binding factors.

Animals↗
PubMed1997

Incidence of delayed onset infection after trabeculectomy with adjunctive mitomycin C or 5-fluorouracil treatment.

AIMS/BACKGROUND: The introduction of the adjunctive use of antiproliferatives to trabeculectomy has greatly improved the success rate of this operation. Trabeculectomy with antiproliferative treatment, however, is usually associated with a cystic and thin walled filtering bleb, which may be more susceptible to infection. The objective of this study was to evaluate the incidence, clinical findings, and risk factors of delayed onset, bleb related infection after trabeculectomy with adjunctive mitomycin C (MMC) or 5-fluorouracil (5-FU) treatment. METHODS: The records of 632 glaucoma patients who underwent 966 trabeculectomies, with and without the use of adjunctive MMC or 5-FU treatment, between January 1985 and February 1995 were analysed. The mean follow up period was 3.5 (2.4) years (range 0.1 to 11.2 years). The mean patient age was 54.8 (18.8) years (range 0 to 88 years). RESULTS: Bleb related infection occurred in one of 76 trabeculectomies that did not receive antiproliferatives (1.3%), three of 228 treated with 5-FU (1.3%) trabeculectomies, and seven of 662 treated with MMC (1.1%). Five eyes developed blebitis; six eyes developed endophthalmitis. Bleb related infection developed an average of 3.1 (1.6) (range 0.4 to 6.0) years after trabeculectomy. All eyes had avascular or hypovascular blebs that were cystic in shape before infection and all eyes had reduced intraocular pressure. Early wound leaks and chronic, intermittent bleb leaks were identified to be risk factors for the bleb related infection. CONCLUSION: The incidence of delayed onset, bleb related infection after trabeculectomy with antiproliferative treatment is similar to that after trabeculectomy without antiproliferatives.

Adolescent↗
PubMed1997

Evaluation of Yucatan micropig skin for use as an in vitro model for skin permeation study.

Skin permeation rates of five non-steroidal anti-inflammatory drugs, three of them lipophilic (ibuprofen, indomethacin and ketoprofen) and two hydrophilic (sodium diclofenac and antipyrine), through Yucatan hairless micropig (YMP) full-thickness skin were determined in vitro using Franz-type diffusion cells, and the usefulness of YMP skin as an animal model skin was investigated. Five-month-old YMP skin showed small variation with respect to drug permeation rates, if the region of skin site was the same. But skin from 6-month-old YMPs showed faster and varied permeation rates due to skin defects. In the case of hydrophilic drugs, no effects on permeation due to the region from which the skin was obtained were observed, although higher permeation rates were observed through the flank than through dorsal skin in the case of ibuprofen and ketoprofen. For YMP skin, the permeation coefficients of drugs were lower than those for hairless rat skin, especially for hydrophilic drugs. Compared with reported human data on permeation coefficients, the permeation coefficients of drugs through YMP skin were 1/2-1/8 of those through human skin, regardless of whether the drugs were hydrophilic or lipophilic. YMP skin could be used as an in vitro animal skin model because of the reproducibility of the permeation rate of drugs through this skin and its similarity to human skin.

Administration, Topical↗
PubMed1997

10-year survival rate in 92 patients with invasive bladder carcinoma treated by bladder sparing methods.

The 10-year survival rate was evaluated in 92 patients with invasive bladder cancer (stages T 2 to 4) who were treated between 1966 and 1985 using bladder-sparing methods such as intravesical instillation of antineoplastic agents, transurethral resection, partial cystectomy, arterial infusion chemotherapy, radiation and embolization of the internal iliac artery. The overall 5-year and 10-year survival rates were 68.1% and 53.9% respectively at a median follow-up period of 60 months. The 10-year survival rate for patients with clinical stage T 2, T3a, T3b and T 4 were 83.7%, 58.9%, 50.8% and 0%, respectively. Our data were comparable or superior to those following radical cystectomy combined with pre- and post-operative radiation or chemotherapy. In conclusion, our bladder-sparing conservative method is thought to be an alternative treatment for advanced bladder cancer and provides a favorable survival rate as well as an improved quality of life with preservation of bladder function.

Administration, Intravesical↗
PubMed1996

Low power laser irradiation reduces ischemic damage in hippocampal slices in vitro.

BACKGROUND AND OBJECTIVE: Low power laser irradiation has been reported to reduce injury, promote regeneration, and produce analgesia. While the mechanism is unknown, one hypothesis is that light produces free radicals, which have a beneficial effect at low concentrations. STUDY DESIGN/MATERIALS AND METHODS: We have investigated the effects of low power laser irradiation on the loss of electrical excitability of hippocampal brain slices after a transient exposure to a perfusion medium lacking oxygen and containing reduced glucose concentrations. Injury in this system is known to result at least in part from free radical production. RESULTS: Low power laser irradiation increased the time required for loss of excitability and increased recovery from the ischemic injury. CONCLUSIONS: Low power laser irradiation has acute protective effects against ischemic damage in brain slices.

Animals↗
PubMed1996

Ocular hypotensive mechanism of topical isopropyl unoprostone, a novel prostaglandin metabolite-related drug, in rabbits.

This study was performed to clarify the ocular hypotensive mechanism of topical isopropyl unoprostone (unoprostone), a novel prostaglandin (PG) metabolite-related drug, in the rabbit eye. The intraperitoneal administration of indomethacin (50 mg/kg) 1 hour before administration of topical 0.12% unoprostone partially diminished the intraocular pressure (IOP) reduction, and completely blocked the increase in aqueous PGE2 concentration caused by unoprostone. Aqueous humor dynamics measurements in the unoprostone- and the vehicle-treated contralateral eyes with indomethacin pretreatment revealed that aqueous flow determined by fluorophotometry was not significantly different, 2.3 +/- 0.3 and 2.4 +/- 0.2 microliters/min, respectively; the total outflow facility measurements determined by the two-level constant pressure perfusion method were 0.20 +/- 0.01 and 0.14 +/- 0.01 microliters/min/mmHg, respectively (p < 0.05); the uveoscleral outflow measurements determined by the fluorescein isothiocyanate-dextran perfusion method were 0.49 +/- 0.02 and 0.46 +/- 0.02 microliters/min, respectively (p < 0.05). The magnitude of the IOP reduction induced by unoprostone was estimated to be 5.2 mmHg, which agrees well with the actual IOP reduction. In conclusion, unoprostone lowers the IOP by affecting aqueous outflow pathways, primarily the pressure-dependent conventional pathway and the secondary uveoscleral outflow pathway in rabbits. Endogenous PGs induced by topical unoprostone are also involved in lowering the IOP in rabbits.

Administration, Topical↗
PubMed1996

Haemodynamic effects of combined treatment with molsidomine and propranolol on portal hypertension in conscious and unrestrained cirrhotic rats.

We investigated the systemic and splanchnic haemodynamic effects of combined treatment with molsidomine and propranolol on cirrhotic rats. Liver cirrhosis was produced by repeated intraperitoneal injections of thioacetamide. The blood flow of each organ was measured serially using the radioactive microsphere method in the awake state before and after the administration of each agent. Cirrhotic rats received molsidomine (0-.5 mg/kg), propranolol (0.1 or 0.2 mg/min), both agents or placebo. Combination treatment with molsidomine and 0.1 mg/min propranolol significantly reduced portal pressure compared with molsidomine or propranolol alone (21 +/- 4 vs 15 +/- 3 or 11 +/- 2% P < 0.05). Systemic haemodynamic changes with this combined treatment were mild. This combined treatment slightly inhibited the molsidomine-induced decrease in portal vascular resistance (27 +/- 9 vs 31 +/- 6; NS) and markedly inhibited the molsidomine-induced decrease in splanchnic arterial resistance (7 +/- 6 vs 27 +/- 5% P < 0.05). Compared with low-dose propranolol administration, the combined treatment was associated with a significant decrease in portal vascular resistance (27 +/- 9% decrease vs 2 +/- 2% increase; P < 0.001) and a significant decrease in splanchnic arterial resistance (7 +/- 6% decrease vs 5 +/- 4% increase P < 0.05). The combination of molsidomine and high-dose propranolol (0.2 mg/min) caused a marked reduction in portal venous inflow, mean arterial pressure and cardiac index. We conclude that propranolol enhances the molsidomine-induced decrease in portal pressure by splanchnic vasoconstriction in association with a slight decrease in portal vascular resistance. The combination therapy with molsidomine and low-dose propranolol combination had more beneficial and less harmful effects on systemic and splanchnic haemodynamics and thus appears to be a superior method for treating portal hypertension.

Animals↗
PubMed1996

Endogenous nitric oxide production is augmented as the severity advances in patients with liver cirrhosis.

1. Since endothelium-derived nitric oxide (NO) is a potent vasodilator and degraded into nitrous ions, we measured the serum nitrate ion (NO3-) and the amount of urinary excretions of NO3- as an index for endogenous NO to ascertain whether NO formation is augmented in patients with chronic liver diseases. 2. Using inpatients suffering from chronic liver diseases, serum levels and urinary excretions of NO3- were measured by using high-performance liquid chromatography with an anion exchange column. 3. Among the four patient groups of normal controls, and those with chronic liver diseases such as chronic active hepatitis, compensated cirrhosis, and decompensated cirrhosis the serum level of NO3- showed the highest level in a patient group with decompensated cirrhosis. The amount of urinary excretion of NO3- was significantly increased in both groups of patients with liver cirrhosis compared with the control group and patients with chronic active hepatitis. Patients with chronic active hepatitis did not show any difference between the normal control group. The amount of urinary excretion of NO3- correlated significantly and negatively with the level of serum albumin (P < 0.05) and counts of platelets (P < 0.01) in patients with compensated cirrhosis. 4. These findings suggest that the production of endogenous NO is augmented in patients with liver cirrhosis, particularly in a decompensated subgroup. Increases in the production of endogenous NO correspond to the progress of liver cirrhosis, but not in patients with chronic hepatitis.

Adult↗
PubMed1995

Failure of neuronal ion exchange, not potentiated excitation, causes excitotoxicity after inhibition of oxidative phosphorylation.

Neuronal cell death during impaired energy metabolism is often attributed to increased activity at glutamate receptors, but this increase has not been directly demonstrated. We recorded responses to glutamate and N-methyl-D-aspartate in hippocampal slice CA1 neurons and glia while inhibiting mitochondrial complex II with 3-nitropropionic acid. As the period of inhibition increased, neuronal depolarization following bath application of glutamate (5 mM) or N-methyl-D-aspartate (50 microM) increased dramatically. However, depolarization upon iontophoresis of glutamate and N-methyl-D-aspartate decreased with time. A transient hyperpolarization, reflecting electrogenic sodium pump activity, was present immediately after responses to iontophoretic glutamate agonists. In the presence of the inhibitor, this hyperpolarization decreased and eventually disappeared. Even the repolarization seen upon washing of the iontophoretic or bath application of glutamate or N-methyl-D-aspartate was incomplete. Glial depolarization upon bath application of glutamate increased during inhibition, while glial depolarization upon application of N-methyl-D-aspartate decreased. Application of the N-methyl-D-aspartate antagonists aminophosphonovaleric acid (100 microM) or MK-801 (20 microM) resulted in a delay of further depolarization when applied early during the terminal decay of membrane potential following metabolic inhibition. We conclude that during impaired oxidative phosphorylation the failure of repolarizing mechanisms, not potentiated neuronal depolarization by excitants, is the primary cause of the terminal depolarization. Large glial depolarization increases the demand for neuronal ion exchange which cannot be met in situations of reduced energy metabolism. Our results provide further evidence that acute and chronic blockade of energy metabolism have different effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Separation of protein factors that correct the defects in the seven complementation groups of xeroderma pigmentosum cells.

We fractionated HeLa cell extracts by gel filtration and then micro-injected them into cells derived from the seven complementation groups (A-G) of xeroderma pigmentosum (XP). Distinct fractions that corrected the unscheduled DNA synthesis (UDS) of the complementation group XP cells were identified. The apparent molecular weights corresponding to complementation groups A, B, C, D, E, F, and G were estimated to be 80, 600, 600, 240, 100, 240, and 280 kDa, respectively. These factors were stable in the respective cell lines, the shortest half life being 16 h for the XP-A and XP-G complementing factors. The fraction (80 kDa) that corrected the UDS in XP-A cells also complemented the defect of the XP-A cell extract in the incision of DNA containing a pyrimidine dimer in a cell-free system. The separated fractions will be useful for understanding the molecular nature of these factors and for assigning complementation groups of cells derived from suspected XP patients.

DNA Repair↗
PubMed1995

Augmented endogenous nitric oxide production in partial portal vein-ligated rats.

1. Endothelium-derived nitric oxide (NO) is a potent vasodilator. Because the body oxidizes it to nitrate ions, NO3-, measurement of the serum concentration and the urinary excretion of NO3- may be an index for endogenous NO. We investigated the role of NO on hyperdynamic circulation in cirrhotic and partial portal vein-ligated rats by measuring NO3. 2. Liver cirrhosis was induced by administration of thioacetamide. Systemic and splanchnic haemodynamics and splenic-systemic shunting were determined by tracer microspheres. The concentration of NO3- was measured by using high-performance liquid chromatography with an anioncolumn. 3. We found that systemic and splanchnic hyperdynamic circulation existed to almost the same extent in cirrhotic and in portal vein-ligated rats as compared to the controls and shamoperated rats, respectively. Splenic-systemic shunting was markedly greater in portal vein-ligated rats than in cirrhotic rats. 4. Serum NO3- levels and urinary excretion of NO3- in cirrhotic rats tended to increase as compared to the controls. On the other hand, the levels in portal vein-ligated rats were significantly increased as compared to those of the shamoperated rats, and were significantly and negatively correlated to the splanchnic arterial resistance and total vascular resistance. The amount of urinary excretion of NO3- significantly correlated to splenic-systemic shunting (r = 0.61, P < 0.05) only in portal vein-ligated rats. 5. We suggest that these high levels of NO3- in portal vein-ligated rats relate to the extensive formation of porto-collateral vasculature or acute changes in systemic and splanchnic haemodynamics due to portal vein-ligation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Quantitative RT-PCR assay detecting the transcriptional induction of vascular endothelial growth factor under hypoxia.

Quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay was used to examine the induction of vascular endothelial growth factor (VEGF) transcript in human osteosarcoma cells, MG-63, under hypoxic culture condition. Using this assay system, the expression of VEGF mRNA was estimated eight-fold higher when cells were cultured under hypoxic condition. Transcription level of hypoxanthine phosphoribosyl transferase (HPRT) mRNA was also examined as an internal control. HPRT mRNA level under hypoxia was reduced to one fourteenth. Secretion of VEGF into the cell culture medium was implied by its stimulating activity on the growth of mouse vascular endothelial cultured cells in vitro.

Aerobiosis↗
PubMed1994

The addition of 5'-coding information to a 3'-directed cDNA library improves analysis of gene expression.

Large-scale sequencing of a 3'-cDNA library permits one to analyse gene expression profiles in various tissues. However, many such sequences lack enough information about the encoded proteins. To overcome this problem, we tested a new library, consisting of a 3'-directed cDNA sequence fused to a to a 5' sequence of about 300 bp. Such 'joint molecules' of about 600 bp were amplified by PCR and directly sequenced. About 40% of these joint molecules included the 5' and 3' terminal portions of the mRNA, and most of the remaining clones contained the middle portion and 3' end of the mRNA. The upstream sequences contained sufficient information with which to search for similarity, ORFs, motifs and hydropathy, thus allowing the mRNAs to be categorized and their functions predicted. The rapid categorization of the cDNAs will help to sort those clones that merit further analysis.

Amino Acid Sequence↗
PubMed1994

Chromosomal assignment of HepG2 3'-directed partial cDNA sequences by Southern blot hybridization using monochromosomal hybrid cell panels.

Large-scale sequencing of a 3'-directed cDNA library from the human liver cell line HepG2 has generated several hundred species of cDNA gene signatures, about 85% of which identify novel genes. They are useful molecular landmarks for human genome mapping. We used 160 of these novel signatures as probes for Southern hybridization to human DNA. We then identified the copy number of the corresponding genes and assigned them to chromosomes, with reference to monochromosomal hybrid cell mapping panels. The distribution profile of the expressing genes among chromosomes suggested that the expressing gene density is not uniform.

Animals↗