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Biomedical subjects

K Nishida

Publications and source records attributed to K Nishida.

At least 271 records · Page 15Linked to original sources
PubMed1995

Delayed posterior interosseous nerve palsy.

A rare case of delayed posterior interosseous nerve palsy that developed 39 years after an unreduced anterior dislocation of the radial head is reported. The posterior interosseous nerve was compressed and narrowed at the arcade of Frohse. Radial head resection and release of the arcade was done. The paralysis continued to recover 6 weeks after operation. The nerve, at the arcade of Frohse, was susceptible to compression by the dislocated radial head, especially in the supinated position. Repeated supination and pronation movement over time may have led to developmental changes that caused the delayed nerve palsy.

Adult↗
PubMed1995

Different effects of absorption promoters on corneal and conjunctival penetration of ophthalmic beta-blockers.

PURPOSE: The purpose of this study was to investigate the improvement in corneal penetration of ophthalmic beta-blockers of various lipophilicities afforded by absorption promoters and to compare the corneal against conjunctival penetration in response to absorption promoters. METHODS: The penetration of the beta-blockers, atenolol, carteolol, tilisolol, timolol, and befunolol, in the presence of absorption promoters, across the isolated corneal and conjunctival membranes of albino rabbits was measured using a two-chamber glass diffusion cell. EDTA, taurocholic acid, capric acid, and saponin were used as the absorption promoters. RESULTS: The absorption promoters significantly increased the corneal permeability of most beta-blockers, especially the hydrophilic agents. The absorption promoters also enhanced the conjunctival permeability of beta-blockers, although their effect in promoting conjunctival penetration was less than that on corneal penetration. There was a differing penetration of instilled beta-blockers in the cornea and conjunctiva in response to absorption promoters. Capric acid and saponin showed significant promoting action on corneal penetration, but not on conjunctival penetration. Taurocholic acid had a significant effect on conjunctival penetration but not on corneal penetration. Saponin caused slight irritation. CONCLUSIONS: Absorption promoters can improve the ocular delivery of beta-blockers and a selective use of absorption promoter can improve the extent and pathway of drug ocular absorption.

Absorption↗
PubMed1995

p53 nuclear immunostaining and gene mutations in non-small-cell lung cancer and their effects on patient survival.

BACKGROUND: p53 gene mutations are known to occur in about half of all non-small-cell lung cancer (NSCLC) cases. Mutations of the p53 gene usually but not always lead to an increased half life of the p53 protein, and result in a nuclear accumulation of protein which can be detected by immunohistochemistry (IHC). Controversy still exists as to whether the presence of an aberration of the p53 gene or protein is a poor prognostic indicator in patients with NSCLC. PATIENTS AND METHODS: DNA samples and paraffin blocks were obtained from 129 patients of 143 consecutive patients who underwent a pulmonary resection during a 22-month period from July 1991 to April 1993. Mutations of the p53 gene occurring at exons 5-8 were detected by a polymerase chain reaction (PCR)/single strand conformation polymorphism (SSCP) assay, while the nuclear accumulation of the p53 protein was detected by immunohistochemistry. RESULTS: Of the patients studied, 35% had mutations and 54% showed overexpression, when we defined a positive case as being one in which more than 10% of the tumor cell nuclei were stained. There was a 59.5% concordance between the p53 gene mutations and p53 immunopositivity. p53 immunopositivity in adenocarcinoma and any p53 abnormality (i.e. p53 immunopositivity and/or mutation) in adenocarcinoma were a poor prognostic indicator. However, Cox's proportional hazards model indicated that the stage was the only significant prognostic factor. CONCLUSIONS: p53 immunopositivity and mutations of the p53 gene are frequently seen in NSCLC. They are considered to be mutually related but may sometimes represent a different aspect of p53 abnormality. p53 alteration may be a poor prognostic indicator only in a subset of patients with NSCLC, especially for adenocarcinoma.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Flow cytometric analysis of nuclear DNA content in the endoscopic biopsy tissues of gastric cancer.

The nuclear DNA content was measured by flow cytometry in gastric cancer patients using endoscopically biopsied tissue specimens. When the specimens were classified into diploid and aneuploid according to the DNA histogram, 56% (65/117) of the specimens were aneuploid, and advanced cancer was clearly more often aneuploid than early cancer. The frequency of aneuploidy appeared to be higher as the histologic depth of cancer was greater. Noncancerous tissues of the stomach were mostly diploid. The nuclear DNA ploidy pattern in gastric cancer cells could be analyzed by using endoscopic biopsy samples and this flow cytometric investigation would be possibly contributive to further characterization of gastric cancer in the diagnostic procedure of malignancy.

Adult↗
PubMed1995

Effect of phenytoin on smoke inhalation injury in sheep.

To determine whether the anti-inflammatory effects of phenytoin might reduce cardiopulmonary dysfunction we studied the effects of phenytoin treatment on acute lung injury induced by smoke inhalation. Twenty-one chronically instrumented sheep were observed for 24 h after smoke inhalation injury. Myocardial contractility was evaluated by left ventricular end-systolic pressure-diameter relationship (LVESPDR) with a pair of ultrasonic transducers and strain-gauge transducer. In the control group (n = 6), uninjured sheep were given a bolus of phenytoin (12.5 mg/kg). Smoke-insufflated sheep were divided into nontreatment (n = 7) and phenytoin (n = 8) groups. Phenytoin alone had no effects in uninjured sheep except an early rise in heart rate and LVESPDR. In the group given smoke without treatment, there was a significant increase in pulmonary artery pressure and pulmonary vascular resistance index and a decrease in cardiac index. Pulmonary vascular changes were attenuated by treatment with phenytoin. Pulmonary transvascular fluid flux was evaluated by using a lung lymph fistula. LVESPDR fell in the smoke group but not in the group given phenytoin. There was a marked increase in lung lymph flow with smoke inhalation but this phenomenon was not affected by phenytoin treatment. In conclusion, phenytoin treatment reduced early hemodynamic depression.

Animals↗
PubMed1995

Absorption of phenol red and bromphenol blue as model drugs from the peritoneal cavity around the liver surface in rats.

The importance of the injection site on the pharmacokinetics of phenol red and bromphenol blue as model drugs after intraperitoneal administration into rat was examined. Their absorption rate from the peritoneal cavity was faster after intraperitoneal administration to the liver surface than that after intraperitoneal administration to the distal small intestine, as shown by the increase in maximum concentration and decrease in mean residence time in plasma. A similar tendency was observed in the biliary excretion pattern. The enhanced absorption rate was supported by the significantly smaller amount of both drugs remaining in the peritoneal cavity at 15 min after liver surface administration than that after small intestine administration. The liver concentration of the model drugs at 15 min after liver surface administration was 1.5-2.0 times that after small intestine administration. Accordingly, liver surface administration was shown to be effective with good absorption and efficient drug delivery to the liver.

Absorption↗
PubMed1995

Mechanism for drug absorption from rat-liver surface membrane: effect of dose and transport inhibitors on the pharmacokinetics of phenol red.

We examined the effect of dose and transport inhibitors on the pharmacokinetics of phenol red as a model drug after application to rat liver surface in-vivo, employing a cylindrical glass cell (i.d. 9 mm, area 0.64 cm2), to elucidate the mechanism for drug absorption from liver surface membrane. Absorption ratios of phenol red in 6 h were determined to be 91.1, 91.8 and 89.9% at a dose of 0.3, 1 and 3 mg, respectively. The AUC value for plasma concentration profile of phenol red was proportional to the dose. It is thus suggested that the absorption process of phenol red from rat liver surface does not approach saturability. The time course of the remaining amount of phenol red in the glass cell obeyed first-order kinetics at a dose of 0.3 mg, and its rate constant Ka was calculated to be 0.0069 min-1. Moreover, no significant difference was seen in the Ka value within the dose range of 0.3-3 mg, which was estimated by curve fitting of the plasma concentration profile of phenol red after application to rat liver surface in the two-compartment model with first-order absorption. 2,4-Dinitrophenol (0.3 mg) and probenecid (0.5 and 1 mg), inhibitors of metabolic energy and anion transport, respectively, had no significant effect on the pharmacokinetics of phenol red after application to rat liver surface. These data demonstrate that a specific transport mechanism such as active transport is not involved in phenol red absorption from rat liver surface membrane.

2,4-Dinitrophenol↗
PubMed1995

Ophthalmic preservatives as absorption promoters for ocular drug delivery.

The effects of ophthalmic preservatives on the drug permeability through isolated ocular membranes of albino rabbits were investigated using a two-chamber glass diffusion cell. Tilisolol and fluorescein isothiocyanate (FITC)-dextrans (average molecular weights 4400 and 9400 Da; FD-4 and FD-10, respectively) were used as model penetrants of ophthalmic beta-blockers and peptide drugs. Preservatives significantly enhanced the corneal penetration of not only tilisolol but also FITC-dextrans. Especially, benzalkonium chloride increased the corneal permeability of FD-4 and FD-10 by 28.8 and 37.1 times, respectively. These results indicate the usefulness of ophthalmic preservatives as absorption promoters for the ocular delivery of beta-blockers and hydrophilic macromolecules. Preservatives also enhanced the conjunctival permeability of tilisolol, FD-4 and FD-10. The promoting effect of preservatives on the conjunctival drug penetration was smaller than that on the corneal one. Preservative increased the ratio of corneal to conjunctival permeability of tilisolol, FD-4 and FD-10. The different responses of corneal and conjunctival drug penetrations to ophthalmic preservatives may be useful to control the extent and pathway for the ocular and systemic absorptions of instilled drugs.

Absorption↗
PubMed1995

Immunohistochemical demonstration of fibronectin in the most superficial layer of normal rabbit articular cartilage.

OBJECTIVE: To locate fibronectin ultrastructurally in the most superficial layer of normal articular cartilage of rabbits, in order to clarify its role in joint physiology. METHODS: Articular cartilage was obtained from the femoral condyle of seven normal adult rabbits and prepared by a method that included tannic acid fixation. Polyclonal antibodies against rabbit fibronectin were used in an immunohistochemical electron microscopic study, without any enzymic digestion but with a pre-embedding method for the transmission electron microscopy. RESULTS: The cartilage surface was successfully preserved by tannic acid fixation. The most superficial layer in electron photomicrographs was approximately 200-300 nm thick, cell free, and appeared to have two parallel components: the more superficial lamina and the deeper lamina. Gold labelled fibronectin lined this layer in immunohistochemical electron photomicrographs. CONCLUSIONS: Fibronectin covering the surface of the articular cartilage may have a role in joint lubrication and protection of the cartilage by binding with the collagenous matrix and hyaluronic acid in synovial fluid. Chondroitin sulphates may act as a charge barrier in close relationship with the collagen fibrils in the deeper lamina. Significant alteration in these functions may be one of the first causal steps leading to destruction of the articular cartilage.

Animals↗
PubMed1995

Preventive effect of dai-saiko-to (da-chai-hu-tang) extract on disrupted hepatic active oxygen metabolism in rats with carbon tetrachloride-induced liver injury.

In order to clarify the preventive action of Dai-Saiko-to (Da-Chai-Hu-Tang) extract (TJ-8) on the progression of acute liver injury in rats intoxicated with carbon tetrachloride (CCl4), we examined the effect of post-oral TJ-8 administration on hepatic active oxygen metabolism following the progression of this liver damage. When TJ-8 (1.0 g/kg body weight) was administered orally to male Wistar rats aged five weeks 2 hrs after i.p. injection of CCl4 (1.0 ml/kg body weight), an apparent liver injury occurred. Significant prevention against the progression of liver injury was found at 24 hrs after injection, judging from the activities of serum transaminases, indexes of liver cell damage. Liver cytosolic superoxide dismutase (SOD) activity decreased 2 and 24 hrs after CCl4 injection, while liver cytosolic catalase and glutathione reductase (GSSG-R) activities decreased 24 hrs after the injection. At 2 and 24 hrs after CCl4 treatment, liver cytosolic Se-containing glutathione peroxidase (GSH-px) activity did not change and liver cytosolic glucose-6-phosphate dehydrogenase (G-6-PDH) activity increased. Post-oral TJ-8 administration significantly ameliorated decreases in liver SOD, catalase, and GSSG-R activities at 24 hrs after CCl4 injection, but did not affect liver Se-GSH-px and increased liver G-6-PDH activities at 24 hrs after the injection. Although increased liver lipid peroxide level and decreased liver reduced glutathione and ascorbic acid levels were observed 2 and 24 hrs after CCl4 injection, post-oral TJ-8 administration significantly prevented these changes found at 24 hrs after injection. These results indicate that post-oral TJ-8 administration can prevent the progression of acute liver injury in CCl4-injected rats by inhibiting enhanced lipid peroxidation and by improving disrupted active oxygen metabolism in the injured liver.

Administration, Oral↗
PubMed1995

Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress.

Shear stress enhances expression of Ca(2+)-calmodulin-sensitive endothelial cell nitric oxide synthase (ecNOS) mRNA and protein in bovine aortic endothelial cells (BAEC). The present studies were performed to investigate mechanisms responsible for regulation of ecNOS mRNA expression by shear stress and to determine if this induction of ecNOS mRNA is accompanied by an enhanced nitric oxide (NO) production. Shear stresses of 15 dyn/cm2 for 3-24 h resulted in a two- to threefold increase of ecNOS mRNA content quantified by Northern analysis in BAEC. Shear stresses (1.2-15 dyn/cm2) for 3 h resulted in an induction of ecNOS mRNA in a dose-dependent manner. In human aortic endothelial cells, shear stresses of 15 dyn/cm2 for 3 h also resulted in ecNOS mRNA induction. In BAEC, this induction in ecNOS mRNA was prevented by coincubation with actinomycin D (10 micrograms/ml). The K+ channel antagonist tetraethylammonium chloride (3 mM) prevented increase in ecNOS mRNA in response to shear stress. The ecNOS promotor contains putative binding domains for AP-1 complexes, potentially responsive to activation of protein kinase C (PKC). However, selective PKC inhibitor calphostin C (100 nM) did not inhibit ecNOS induction by shear stress. Finally, production of nitrogen oxides under both basal conditions and in response to the calcium ionophore A-23187 (1 microM) by BAEC exposed to shear stress was increased approximately twofold compared with cells not exposed to shear stress. These data suggest that ecNOS mRNA expression is regulated by K+ channel opening, but not by activation of PKC, and that shear not only enhances ecNOS mRNA expression but increases capacity of endothelial cells to release NO.

Animals↗
PubMed1995

Effect of albumin on the absorption of phenol red, bromphenol blue and bromosulphonphthalein as model drugs from the liver surface membrane in rats.

The effect of bovine serum albumin (BSA) on drug absorption from the liver surface in rats was examined by using three organic anions (phenol red, bromphenol blue and bromosulphonphthalein) as model drugs which have a high affinity for albumin. The binding ratio of the model drugs (3 mg/ml in phosphate buffer) to BSA varied widely at a BSA concentration of 0.1--10% (w/v). The model drugs (3 mg/ml x 0.1 ml) with or without BSA were applied to the rat liver surface in vivo employing a cylindrical glass cell (i.d. 9 mm, area 0.64 cm2). The absorption ratios of the model drugs from the rat liver surface at 6h, calculated from the amount recovered from the glass cell, decreased with an increase in BSA concentration. A similar trend was observed with biliary recovery of the model drugs. A marked reduction in the absorption ratio was seen with bromosulphonphthalein, which has the highest binding activity to BSA among the three organic anions. Accordingly, protein binding appears to be a significant factor with respect to the drug absorption from the liver surface.

Absorption↗
PubMed1995

Effect of ophthalmic preservatives on serum concentration and local irritation of ocularly applied insulin.

We previously compared hypoglycemic responses after the instillation of insulin formulations. A hypoglycemic response was actually observed after an instillation of insulin with ophthalmic preservatives. In the present study, in order to evaluate the usefulness of insulin formulation containing ophthalmic preservatives, a serum concentration of insulin and an irritation to the eye were investigated after instillation of the insulin formulation in albino rabbits. The ophthalmic preservatives used were benzalkonium chloride, paraben, 2-phenylethanol, benzyl alcohol and sorbic acid. As a result, ophthalmic preservatives, especially benzalkonium chloride and paraben, increased the serum concentration of insulin. The insulin concentration showed a significant correlation with the hypoglycemic response reported previously. This result indicates that ophthalmic preservatives increase the absorption of ocularly applied insulin, and the absorbed insulin decreases serum glucose concentration. The insulin formulation with preservatives showed little irritation on rabbit eyes according to blinking measurements. These results indicate that ophthalmic preservatives are useful for the systemic delivery of ocularly applied insulin.

Administration, Topical↗
PubMed1995

[Effectiveness of continuous good dental health cares contributing to 20 teeth retained].

This study was made to demonstrate what kinds of continuous care for dental health have teeth remained even at the elderly time. Questionnaires were mailed to 632 men retired from a company at the age of 60s or more, September-October in 1992. Of 424 cases recovered (67.1%), 414 (97.6%) i.e., 185 cases at the age of 60s, 172 of 70s, and 57 of over 80s, were subjected to analysis. All the subjects were classified into two groups. One is the group who has 20 teeth or more, the other having 19 teeth or less. Furthermore, each group was classified into three groups. The first group was no dental health care [DHC] group (group 1), the second one was starting DHC at the age of 20s or 30s (group 2), the third one was doing at the age of 40s or 50s (group 3). These groups were compared with each other group. Items related to dental health were developed by ourselves. Chi-square test was done to prove the relationship between the starting time of continuous DHC and retention teeth of 20 teeth or more in the three age groups. The following three items related to dental health care may contribute significantly to retention teeth of 20 teeth or more at each age group, 1) changing to new brush every 2 or 3 months (p < 0.01), 2) making an effort to have hard foods (p < 0.01), 3) having calcium-rich foods (p < 0.05).

Adult↗
PubMed1995

Strongly anionic sites in peripheral axons of the rat sciatic nerve: light and electron microscopic detection using cationic colloidal iron.

Anionic sites in the rat sciatic nerve were studied by light and electron microscopy using a fine-granular cationic colloidal iron staining method (Murakami et al., 1986). The axon, as well as the endoneurium, the epineurium and the basement membrane of Schwann cells, were all confirmed to react strongly to the cationic colloidal iron even at a pH value of 1.0-2.0. Prior hyaluronidase digestion decreased the colloidal strain of the epineurium; chondroitinase ABC weakened that of the endoneurium and the basement membrane of Schwann cells. However, as axons retained stainability with cationic colloidal iron even after combined digestion with hyaluronidase, chondroitinase ABC, heparitinase and keratanase, the authors consider sulfated glycoconjugates and not those substances which are digestible with such common enzymes. The acid groups ionized at pH 1.0 are most likely sulfate groups. Methylation deprived the axon of the reactivity to cationic colloidal iron staining, and even subsequent saponification could not recover this reactivity to its full extent. In the axon, electron microscopy revealed a deposition of colloidal iron on the external surfaces of microtubules and neurofilaments in the axoplasm and of very fine filaments connecting them. This highly negatively charged intra-axonal network could also serve toward a supportive function in maintaining the spatial distribution of microtubules either mechanically or through electrostatic repulsion or, possibly, serve as an intra-axona cation exchange reservoir.

Animals↗
PubMed1995

Localization of the glycosaminoglycans in the synovial tissues from osteoarthritic knees.

Localization of the glycosaminoglycans (GAG) was examined in the synovial membranes of patients with osteoarthritis under light microscopy using a fine cationic colloidal iron staining method combined with enzymatic digestion. Our staining method was very useful for demonstrating the difference in the localization of GAG in regions of the inflammatory site in the osteoarthritic synovial membrane. Hyaluronic acid was mainly located in connective tissues in the surface intercellular and perivascular spaces, chondroitin sulfate A/C in the highly fibrous part of and connective tissue around blood vessels, dermatan sulfate (chondroitin sulfate B) in the subsurface interstitium and vascular endothelial cells and heparan sulfate in part of vascular endothelial cells. No keratan sulfate was detected. GAG is reported to have an important role in cell movement, adherence and aggregation in the inflammatory sites. These findings should be useful for understanding the role of GAG in physiological and pathologic processes of secondary synovitis.

Adult↗
PubMed1995

Transforming growth factor-beta 1, -beta 2 and -beta 3 mRNA expression in human cornea.

The expression of TGF-beta 1, TGF-beta 2 and TGF-beta 3 precursors mRNA transcripts in in vivo human corneal cells were studied. Complementary DNA (cDNA) was generated from poly A+RNA extracted from in vivo human corneal epithelial cells, stromal keratocytes and endothelial cells. With the cDNAs as template, polymerase chain reaction (PCR) was carried out using specific primers of TGF-beta 1, TGF-beta 2 and TGF-beta 3 precursors, synthesized by choosing specific nucleotide sequences in the latency-associated peptide region of each precursor. Southern blot analysis of the PCR products was carried out. In corneal epithelial cells, TGF-beta 2 mRNA transcript was strongly expressed; TGF-beta 1 and -beta 3 mRNA transcripts were also expressed; stromal keratocyte samples expressed TGF-beta 1 and -beta 2 mRNA transcripts but not TGF-beta 3 mRNA transcript. Endothelial cells expressed all three transcripts. The present study, together with the authors' previous immunohistochemical study demonstrates that both protein and mRNA of TGF-beta 2-LAP are present in human corneal epithelium, indicating that TGF-beta 2 may play a crucial role in corneal epithelial cell layers.

Aged↗