Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 685 records · Page 38Linked to original sources

PubMed1992

Preferential increase of heterochromatin in venular endothelium of lung in mice after administration of dimethylarsinic acid, a major metabolite of inorganic arsenics.

Dimethylarsinic acid (DMAA) administration induced the preferential increase of the heterochromatic area forming the inside of the interphase nucleus. A histopathological study of the lung and liver in mice after DMAA administration was carried out by transmission electron microscopy. Ultrastructural alterations in the endothelial nuclei of the alveolar wall were observed 12-48 h after administration. Heterochromatin tended to collect in a dense, compact mass lining the inner walls of the nucleus. A significant increase in heterochromatin induced by DMAA administration was observed by morphometric analysis. However, no substantial differences appeared in the sinusoidal endothelium of the liver. This study suggests that the much greater induction of morphological alterations, such as increased heterochromatin, in lung endothelial nuclei than in the liver might explain the high risk of lung cancer by arsenics, and that there may be a close relationship between heterochromatin alteration and DNA damages.

Animals↗

PubMed1992

Accumulation of cardiac lipofuscin depends on metabolic rate of mammals.

The accumulation of lipofuscin, an important phenomenon during aging, suggests that the sexual maturity (puberty) of mammals is a starting point of the aging process. The rate of cardiac lipofuscin accumulation was not correlated linearly with maximum life span of mammals, but the correlation was a power function of the maximum life span. The rate of lipofuscin accumulation statistically correlated with the specific metabolic rate, and inversely correlated with the brain weight of mammals. The first appearance of lipofuscin showed a good correlation with the brain weight. However, the slope of the line was different between primates and domestic and laboratory animals. From these results, it is suggested that the accumulation of cardiac lipofuscin is dependent on the specific metabolic rate of mammals.

Aging↗

PubMed1992

Modification of immunopharmacological activities of synthetic monosaccharide lipid A analogue, GLA60, by lysozyme.

Recent studies by our group suggested that lysozyme has a high affinity for bacterial lipopolysaccharide (LPS) of both the smooth and rough forms, and inhibits various immunomodulatory activities of LPS. GLA60 is a synthetic monosaccharide analogue of bacterial lipid A well known as having most of the activities of lipid A with very low toxicity. In this study, we characterized the interaction of lysozyme with GLA60 in comparison to that with Escherichia coli 0111 LPS (smooth form) by means of an immunopharmacological approach. Using dansylated lysozyme (DNS-LZM) as a probe, LZM was found to bind to GLA60. The mitogenic and polyclonal B-cell activating activities were significantly reduced by complex formation. However, there was no inhibitory effect on GLA60 induced production of IL-1 and TNF of macrophages. Interestingly, the activities of macrophages induced by the complex were found to be significantly higher than those induced by GLA60 itself. In contrast, the activities of 0111 LPS were significantly inhibited by LZM. Since the GLA60-LZM complex produced a turbid suspension but the 0111 LPS-LZM complex remained soluble, we consider that the activities of GLA60 alone were mediated by the common functional LPS receptor for dispersed form in both macrophages and B-lymphocytes, but activation of macrophages by the complex was mediated either by another LPS receptor not present in B-lymphocytes or through the phagocytic function of macrophages.

Adjuvants, Immunologic↗

PubMed1992

Clinicopathologic studies on human epithelial autografts and allografts.

We compared the survival of cultured epithelial allografts and epithelial autografts applied to donor sites for split-thickness skin grafts. Before grafting, cultured epithelium was devoid of Langerhans cells (LCs) or lymphoid cells by immunohistochemical and electron microscopic examinations. The autografts attached to the wounds permanently, without any clinical evidence of rejection. In contrast, allografts, which were mismatched for MHC and blood-type antigens, appeared to adhere firmly only until day 7. By the second week, signs of graft rejection were apparent: The graft changed color, and the underlying dermis underwent "microerosion" and denudation. By the third week, the area formerly occupied by the allograft had the same coloration as ungrafted wounds and apparently had undergone reepithelialization by the host. Immunohistochemical and ultrastructural studies clearly demonstrated that host Langerhans-like cells (without Birbeck granules) appeared in both autografts and allografts. However, these cells were numerous and distributed widely throughout allografts, whereas they were scarce and confined to the basal layer of autografts. Typical Langerhans cells (containing Birbeck granules) were present in the prickle-cell layer of autografts by day 7. The present study strongly indicates that allografts of cultured epithelium are rejected. Furthermore, given the known ability of Langerhans-like cells to function as accessory cells in T-cell activation, our results point to a role for host Langerhans-like cells in immunologically mediated rejection of the epithelial allografts.

Adult↗

PubMed1992

Dermal patch anaesthesia for venous cannulation with 10% lignocaine gel containing glycyrrhetinic acid monohemiphthalate disodium as an absorption promoter.

The clinical efficacy of transdermal 10% lignocaine gel mixture containing 3% w/w glycyrrhetinic acid monohemiphthalate disodium as an absorption promoter was evaluated at venous cannulation in 17 paediatric (6-11 years) and 17 adult (29-65 years) patients. After about 60 min of occlusive application, the mean (SD) pinprick pain score was 0.7 (0.7) in the paediatric group, compared with 1.4 (1.3) in the adults (p less than 0.05). Twenty-five patients (14 children and 11 adults) who had a pinprick score of 0 or 1 underwent venous cannulation without intradermal local anaesthetic. The mean (SD) pain scores at venepuncture showed no significant differences between children and adults.

Administration, Cutaneous↗

PubMed1992

Transport of paraquat and mexiletine from the blood into the rat intestinal lumen and peritoneal cavity.

Transport of paraquat and mexiletine from the blood into the intestinal lumen and the peritoneal cavity was examined after their intravenous administration (paraquat: 20 mg kg-1, mexiletine: 10 mg kg-1) to rats. The average amounts of paraquat transferred into the intestinal lumen and the peritoneal cavity were 1.39 and 22.8% of the dose in 120 min, respectively. The average amounts of mexiletine transferred into the intestinal lumen and the peritoneal cavity were 6.1 and 2.5% of the dose in 120 min, respectively. The transfer rate of 3H2O into the peritoneal cavity after intravenous administration (1.85 MBq) was greater than that into the intestinal lumen. In view of the hydrophilic nature of paraquat cation, a solvent drag effect due to movement of water might contribute to transport of paraquat from the blood to the peritoneal cavity. Differences in transport behaviour across the two membranes could be due to differences in the geometrical factors such as the surface area and the distribution of blood vessels. Differences might also be due to differences in physicochemistry and pharmacological effects of both substances.

Animals↗

PubMed1992

The effect of dinoprost on transport of water and imipramine through rat small intestinal membranes.

The relation between transmucosal fluid movement and its effect on absorption and exsorption of imipramine was studied with the in-situ single-pass perfusion technique in rats. Dinoprost (prostaglandin F2 alpha, PGF2 alpha) caused a dose-related inhibition of both absorption and secretion of water across the intestinal membrane. When PGF2 alpha was infused at a rate of 5 mumols kg-1 h-1, the absorption rate of water decreased from 51.7 to 21.5 mL h-1 and the secretion rate decreased from 48.9 to 26.8 mL h-1. Net water flux changed from net water absorption (0.9 mL h-1) to net water secretion (5.33 mL h-1) by infusion of PGF2 alpha. However, absorption and exsorption of imipramine were little affected by infusion of PGF2 alpha. The absorption rates of imipramine were 3.03 and 2.36 mg h-1 in the absence and presence of PGF2 alpha, respectively. Furthermore, the average amounts of imipramine exsorbed into the intestinal lumen in 2 h were 7.82 and 8.10% in the absence and presence of PGF2 alpha, respectively. Infusion of PGF2 alpha also enhanced motility of the small intestine compared with the control. From these results, it appears that PGF2 alpha has no effect on the absorption and exsorption of imipramine across the intestinal membrane although it is reasonable to use PGF2 alpha in the case of patients with overdoses of drugs which decrease gastrointestinal motility.

Animals↗

PubMed1992

[Tsutsugamushi disease found in Haruna District, Gunma Prefecture--evaluations of the clinical features and the outbreak pattern].

From November to December in 1990, 7 cases of tsutsugamushi disease were found first in the southern foot of Mt. Haruna of Gunma Pref., Japan. The present study was conducted to clarify the clinical features and the outbreak pattern of rickettsial infection in this area. All the patients consisting of 6 males and 1 female farmers were admitted to our hospital, complaining of high fever, chills and skin rash on 5-12 days after working in the field. Based on laboratory examinations and one (or two) typical eschar, a tentative diagnosis of tsutsugamushi disease was made and all patients became better soon after the therapy with intravenous administration of minocyclin (200 mg/day). The high titer of serum antibody to Karp type Rickettsia (Orientia?) tsustugamushi was detected by an immunoperoxidase test (IP) in most of the patients, and also a Karp-like strain was isolated from only one patient, probably due to low virulence to mice. The agricultural areas along the Agatuma and Nakuta rivers in the northern foot of Mt. Haruna have been well known as the most endemic foci of the disease in Gunma Pref. Nevertheless, it was suggested that outbreaks of the disease might be potentially wide-spread throughout this Pref., when the prevalences of the disease were evaluated as incidences to a hundred thousand inhabitants or adjusted by the density of agricultural populations of each administrative divisions. As most of the patients in Gunma Pref. have been officially reported in autumn, a statistical trial indicates that there is a significant correlation between the levels of temperature and outbreaks of the disease in autumn.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

[A study of enhancing effects of monocyte culture supernatant on polymorphonuclear neutrophils-chemiluminescence--comparison between normal controls and collagen disease patients].

Priming effect of monocyte culture supernatant on polymorphonuclear neutrophils (PMN)-chemiluminescence (CL) was studied in patients with systemic lupus erythematosus (n = 11) and mixed connective tissue disease (n = 4). In normal controls, N-formyl-methionyl-leucyl-phenylalanine (FMLP) induced PMN-CL was enhanced when PMN were previously incubated for 15 minutes with monocyte culture supernatant (MS) or T lymphocyte culture supernatant (TS) or T lymphocyte culture supernatant (TS). The enhancing effect of MS on PMN-CL was greater than that of TS. This enhancing effect of MS was inhibited by adding of dexamethasone (1 microgram/ml) during the culture. Recombinant human TNF also enhanced PMN-CL as well as MS. When compared the enhancing effects of MS between patients and normal controls, that of patients under corticosteroid therapy (average prednisolone dose 39.5 mg/day) was reduced significantly. Thus, we concluded that the cytokines from monocyte contributed PMN phagocytosis of invading microorganisms, and that this monocyte-mediated PMN phagocytosis was suppressed partly by corticosteroids in collagen disease.

Adolescent↗

PubMed1992

Infection of macrophages with Legionella pneumophila induces phosphorylation of a 76-kilodalton protein.

Infection of peritoneal macrophages from susceptible A/J mice with Legionella pneumophila induced phosphorylation of a 76-kDa protein. The phosphorylation occurred when macrophages were infected with a virulent strain of L. pneumophila but did not occur when they were infected with an avirulent strain or with other bacteria such as either Pseudomonas aeruginosa or Salmonella typhimurium. Also, no phosphorylation of this protein was observed when macrophages were stimulated with either lipopolysaccharide or phorbol myristate acetate. However, phosphorylation did occur in macrophages infected with a virulent strain of L. pneumophila and treated with either erythromycin to inhibit growth or with cytochalasin D to inhibit uptake of L. pneumophila by macrophages. These results support the view that phosphorylation of this protein occurs during the early phases of interaction between L. pneumophila and macrophages. The role of this specific protein in the recognition, intracellular uptake, and growth of L. pneumophila in permissive macrophages remains to be clarified.

Animals↗

PubMed1992

Assay for opsonin activity based on chemiluminescence of a Cypiridina luciferin analog.

Opsonin activity (OA) was investigated in serum samples from cord blood of 11 full-term newborn infants and 12 healthy adult volunteers by the method of luminol-dependent chemiluminescence (L-CL) and Cypiridina luciferin analog-dependent chemiluminescence (CLA-CL) together with the measurement of complement components (C3, C4, C3A and properdin). CL and complement components of cord samples were significantly lower than that of healthy adult blood. CLA-CL showed a significant correlationship to C3 and C3A. L-CL also displayed a significant correlationship to C3A but the relationship to C3 was not significant. From these results, when OA is measured by CL, CLA-CL is preferred to L-CL as a technique.

Adult↗

PubMed1992

A comparative study of transdermal 10% lidocaine gel with and without glycyrrhetinic acid monohemiphthalate disodium for pain reduction at venous cannulation.

The clinical benefits of transdermal 10% lidocaine base gels with and without 3% glycyrrhetinic acid monohemiphthalate disodium (GAMHPh) for reduction of pain at venous cannulation were compared in a randomized, double-blind fashion in 24 surgical patients. After about 60 min of occlusive transdermal application, the mean pinprick pain score (1.3 +/- 1.5) in the GAMHPh group (n = 12), graded by noting the number of painful pinpricks out of five, was significantly less than that (2.5 +/- 1.7) in the control group (n = 12) (P less than 0.05). Twelve patients (eight in the GAMHPh group and four in the control group) who had a pinprick score less than 1 underwent venous cannulation without intradermal injection of a local anesthetic. The pain score at venipuncture, graded by the patients on a scale of 5, was significantly less in the GAMHPh group than that in the control group (1.9 +/- 1.1 vs 3.3 +/- 1.0, P less than 0.05). Erythema observed in 8 of the 24 patients was the only adverse local reaction. Addition of 3% GAMHPh to the lidocaine gel is useful in promoting transdermal lidocaine absorption.

Administration, Cutaneous↗

PubMed1992

Skin pretreatments for shortening onset of dermal patch anesthesia with 3% GA MHPh 2Na-10% lidocaine gel mixture.

Three types of skin pretreatments (stripping with adhesive tape, scrubbing with Skin-Pure jelly, and cleaning with benzine) were studied in 21 volunteers to determine whether the pretreatments could shorten the application period of transdermal 3% GA MHPh 2Na-10% lidocaine gel. Before application of the gel, each subject received skin pretreatment on the volar surface of one forearm. Then, the lidocaine gel soaked in a round sponge was applied on both the pretreated area of the forearm and the unpretreated contrast area of the other forearm. A pain score was obtained from each subject at 30, 45, 60, and 75 min after placement of the dermal patch by noting the number of painful pinpricks of five delivered. The mean pain scores on the pretreated side were significantly lower at 30, 45, and 60 min in the stripping study group and at 45 and 60 min in the cleaning study group, compared with the corresponding scores on the unpretreated side (P less than 0.05). Skin pretreatments, such as stripping and cleaning, are useful for shortening the onset of the dermal patch anesthesia.

Administration, Cutaneous↗

PubMed1992

Renin inhibitors. II. Synthesis and structure-activity relationships of N-terminus modified inhibitors containing a homostatine analogue.

The synthesis and structure-activity relationships of N-terminus modified renin inhibitors containing the homostatin analogue, (2RS,4S,5S)-5-amino-2-ethyl-4-hydroxy-7-methyloctanoic acid, are described. The compounds having a 3-alkyl (or aryl)sulfonylpropionyl residue at the N-terminus are found to be potent inhibitors which contain two amino acids. (2RS,4S,5S)-N-Isobutyl-5-[N-[(2S)-3-ethylsulfonyl-2-(1- naphthylmethyl)propionyl]-L-norleucyl]-amino-2-ethyl-4-hydroxy-7- methyloctanamide (20) has an IC50 of 0.5 nM against human plasma renin and the oral bioavailability of 20 is 0.73% in rats. Interaction between renin and the N-terminus of 1 and 20 is discussed in molecular modeling studies.

Amino Acids↗

PubMed1992

Renin inhibitors. I. Synthesis and structure-activity relationships of transition-state inhibitors containing homostatine analogues at the scissile bond.

The synthesis and structure-activity relationships of transition-state renin inhibitors containing the homostatine analogues at the scissile bond are described. These inhibitors incorporate the amino acid side chains corresponding to positions 7-12 (P4-P2') of angiotensinogen. Ethyl, 2-hydroxyethyl and 3-hydroxypropyl groups at position 2 of the homostatine analogues (P1') are more effective for increasing potency than the isopropyl group. A combination of residues at P1, P3 and P4 is important for potency and this result suggests that S1, S3 and S4 form a huge hydrophobic core together in renin.

Humans↗

PubMed1992

Factors that determine the in vivo dose-response relationship for stable chromosome aberrations in A-bomb survivors.

An overview is given of the dose-response relationship for stable chromosome aberrations (i.e., translocations and inversions) in the peripheral blood lymphocytes of A-bomb survivors in Hiroshima. Special emphasis is placed on (i) the overdispersion of survivor cases with either unexpectedly high or low aberration frequencies relative to the estimated DS86 kerma values assigned to individual survivors, termed "cytogenetic outliers", and (ii) the correlation of chromosome aberration frequencies with other biological endpoints, such as acute radiation symptoms (severe epilation). A new molecular biological technique, known as fluorescence in situ hybridization (FISH) with composite, whole-chromosome probes to paint differentially the target chromosomes, has facilitated rapid, efficient, and extensive scoring of translocation-type chromosome aberrations in which the target chromosomes are involved. Using this methodology, the observed findings on translocation frequencies in A-bomb survivors have shown that the frequency of stable chromosome aberrations, which have persisted for years without change in frequency in irradiated persons, is indeed useful as an indicator for biological dosimetry.

Chromosome Aberrations↗

PubMed1992

Hepatic Abnormalities in Obesity: comparison between mildly obese cases and morbidly obese cases.

Hepatic morphology and clinical course of mildly obese subjects with abnormal liver tests were determined in comparison with those of surgically treated morbidly obese cases. Twenty mildly obese subjects (mean body mass index, 27.9) with elevated serum transaminase levels were followed up on a low-calorie diet. Nineteen morbidly obese patients (mean body mass index, 39.2) had a surgical biopsy at gastric restrictive surgery. In these two groups, the frequency and the severity of hepatic steatosis and fibrosis were comparable, whereas intralobular cell infiltration was somewhat greater in the mildly obese group. Follow-up studies of the two groups showed remarkable improvement of serum transaminase levels, the extent of which was greater in surgically treated cases. Thus, in mildly obese subjects with abnormal liver tests, (1) hepatic histological abnormalities are not milder than those in morbidly obese cases, and (2) Improvement of serum transaminase levels upon diet therapy is less satisfactory than that in morbidly obese cases treated surgically. It is suggested these two groups may not be in the same spectrum of obesity-related hepatic disorders.

Journal Article↗

PubMed1992

Changes in the properties and composition of zona pellucida of pigs during fertilization in vitro.

Several hundred fertilized pig eggs were prepared by an in vitro fertilization (IVF) technique in which follicular phase ovarian eggs were matured in vitro to metaphase II before incubation with capacitated epididymal spermatozoa for 12 h at 39 degrees C. Parthenogenetic eggs were also prepared by stimulation of the mature eggs with an electric pulse. The zonae were solubilized with 0.2% pronase/phosphate-buffered saline (PBS) or lactic acid/PBS. The time taken for solubilization was 30-40% shorter than for unfertilized eggs, indicating that zona hardening was induced during fertilization. At the same time, the sperm receptor activity of the zona was reduced. Electrophoretic analyses of zona glycoproteins from the ovarian, mature and fertilized eggs revealed that the amount of 90 kDa proteins decreased substantially during fertilization. This fraction could barely be detected in the zonae from parthenogenetic eggs. However, modification with a fluorescent probe showed that the general architecture of the zona remained unchanged during fertilization. These results suggest that the minor 90 kDa proteins are specifically degraded by the protease(s) released from the oocyte at fertilization, thereby leading to the block to polyspermy.

Animals↗