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Biomedical subjects

S Nagata

Publications and source records attributed to S Nagata.

At least 397 records · Page 22Linked to original sources

Validation of continuous wave Doppler-determined right ventricular peak positive and negative dP/dt: effect of right atrial pressure on measurement.

OBJECTIVES: The present study aimed to validate the peak positive and negative values of the first derivative of right ventricular pressure (dP/dt) using Doppler echocardiography and to determine the impact of right atrial pressure on the measurements. BACKGROUND: A pressure gradient between the right ventricle and the right atrium can be obtained by continuous wave Doppler-derived tricuspid regurgitant velocity using the simplified Bernoulli equation. If right atrial pressure fluctuation during systole and isovolumic diastole were small compared with right ventricular pressure changes, right ventricular pressure could be evaluated, and maximal positive and negative dP/dt could also be determined with Doppler echocardiography. METHODS: We investigated 11 patients with a wide range of right atrial pressure with tricuspid regurgitation using simultaneous examination by Doppler ultrasound and catheterization. Hemodynamic conditions were altered by the Valsalva maneuver, and a total of 40 beats were analyzed. RESULTS: There was good correlation between Doppler-derived and catheterization-derived peak positive dP/dt (y = 1.0x - 15.4, r = 0.98, n = 40), irrespective of the level of right atrial pressure. Doppler-derived peak negative dP/dt also showed good correlation with that determined by catheterization (y = 0.9x + 58.2, r = 0.93, n = 40). However, in patients with high right atrial pressure (v wave pressure > or = 10 mm Hg), Doppler-derived peak negative dP/dt tended to show lower values than those from catheterization measurements, except in patients with pulmonary hypertension. CONCLUSIONS: We conclude that right ventricular dP/dt can be estimated by the Doppler method accurately and noninvasively. However, when right atrial pressure is relatively high compared with corresponding right ventricular pressure changes during isovolumic diastole, Doppler-derived peak negative dP/dt might underestimate catheter-derived measurements.

Adult↗

An ICAM-related neuronal glycoprotein, telencephalin, with brain segment-specific expression.

Telencephalin (TLN) is a 130 kd glycoprotein expressed exclusively in neurons of the telencephalon, the most rostral brain segment. In the neurons, TLN is localized to soma-dendritic membrane but not to axonal membrane. In this study, we have cloned cDNA encoding rabbit and mouse TLN. The cDNA-derived primary structure of TLN predicts an integral membrane protein with nine tandem immunoglobulin-like domains in an extra-cellular region, a transmembrane domain, and a short cytoplasmic tail. The distal eight immunoglobulin-like domains of TLN show highest homology with the immunoglobulin-like domains of intracellular adhesion molecules (ICAMs) 1, 2, and 3/R. The structural similarity of TLN with ICAMs provides a new and strong link between immunoglobulin superfamily molecules in the nervous and immune systems. TLN is an example of a dendrite-associated cell adhesion molecule involved in the brain's segmental organization, cell-cell interactions during dendritic development, and maintenance of functional neuronal networks.

Amino Acid Sequence↗

BIG-1: a new TAG-1/F3-related member of the immunoglobulin superfamily with neurite outgrowth-promoting activity.

We have cloned a rat cDNA for a novel brain-derived immunoglobulin (Ig) superfamily molecule, BIG-1, by using PCR based on the amino acid sequences of the two closely related and well-known Ig superfamily members, rat TAG-1 and mouse F3. BIG-1 is a glycosylphosphatidylinositol-anchored membrane protein with six Ig-like domains and four fibronectin type III repeats, belonging to the TAG-1/F3 subgroup. The expression of BIG-1 mRNA is developmentally regulated with the highest level in the adult brain. It is restricted to subsets of neurons such as Purkinje cells of the cerebellum, granule cells of the dentate gyrus, and neurons in the superficial layers of the cerebral cortex. Recombinant BIG-1 protein has a neurite outgrowth-promoting activity when used as a substrate for neurons in vitro. These results suggest that BIG-1 may be involved in the formation and maintenance of neuron type-specific networks in the brain.

Amino Acid Sequence↗

Human Fas ligand: gene structure, chromosomal location and species specificity.

Fas ligand (FasL) is a 40 kDa type II membrane protein belonging to the tumor necrosis factor family, which induces apoptosis by binding to its receptor, Fas. In this report, we isolated the chromosomal gene for human FasL. The human FasL gene consists of approximately 8.0 kb and is split into four exons. The human FasL gene was mapped on chromosome 1q23 by in situ hybridization against human metaphase chromosomes. Human FasL cDNA was isolated by the reverse polymerase chain reaction of mRNA prepared from human activated peripheral blood lymphocytes. Human FasL is a type II membrane protein consisting of 281 amino acids with a calculated M(r) of 31,759. It has an identity of 76.9% at the amino acid sequence level with mouse FasL. Both human and mouse recombinant FasL expressed in COS induced apoptosis in the cells expressing either human Fas or mouse Fas, indicating that FasL fully cross-reacts between human and mouse. A comparison of human and mouse FasL chromosomal genes indicated that a approximately 300 bp sequence upstream of the ATG initiation codon is highly conserved between them. Several transcription cis-regulatory elements such as SP-1, NF-kappa B and IRF-1 were recognized in this region.

Adult↗

Helicobacter pylori colonization in children with gastritis and peptic ulcer. I. The colonization rate and effects of colonization on mucin content and mucosal inflammation in the antrum.

The incidence of Helicobacter pylori infection and effects of H. pylori colonization on mucin content and mucosal inflammation of the antral mucosa were studied quantitatively in 55 Japanese children with suspected gastritis and peptic ulcers (aged 6-16 years, mean 12.3 years). H. pylori was detected, using Warthin-Starry stain, in nine of the 22 cases (41%) with antral histological gastritis, but in none of the 33 histologically normal cases. Five out of seven duodenal ulcer cases showed histological gastritis, and all five cases were H. pylori positive. Severity of gastritis, evaluated by means of gastritis score, was significantly higher in H. pylori positive gastritis cases than in H. pylori negative gastritis cases (5.4 +/- 1.0 vs 3.1 +/- 0.3, P < 0.001). A PAS-AB index, a proportion of the periodic acid Schiff-alcian blue (PAS-AB) positive mucin area to the total epithelial area, was significantly lower in H. pylori positive cases than in H. pylori negative cases, irrespective of the existence of histological gastritis (23.5 +/- 7.6% vs 40.4 +/- 5.5%, 43.5 +/- 4.2%, P < 0.001). The decreased mucin content of gastric mucosa is likely to lead to weakening of an important defensive factor of gastric mucosa. These findings suggest that H. pylori plays an important role in gastritis and peptic ulcers in children, especially in cases with duodenal ulcer.

Adolescent↗

Helicobacter pylori colonization in children with gastritis and peptic ulcer. II. Ultrastructural change of the gastric mucosa.

To evaluate the role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer in children, ultrastructural changes of the gastric mucosa with H. pylori colonization were studied in two pediatric patients with duodenal ulcers. The study demonstrated that H. pylori: (i) colonized the mucous layer covering normal gastric epithelium; (ii) lay atop short, irregular microvilli and at the intercellular junctions of damaged cells; and (iii) adhered firmly by specific junction zone (firm connection) and loosely by filamentous appendages to the epithelial surfaces of cells which lacked evidence of a protective mucous layer. The ultrastructural changes, which become progressively worse from patterns (i) to (iii) mentioned above, suggest that these patterns represent distinct and successive stages of the infection. These findings, therefore, lend support to the notion that H. pylori infection is quite common and may relate to the pathogenesis of gastritis and peptic ulcer in children as well as in adults.

Child↗

[Pharmaceutical dosage form design of copoly (lactic/glycolic acid) microspheres. Mechanism of in vitro release of gentamicin].

The sustained release mechanism of gentamicin (GM) from lactic acid/glycolic acid copolymer (PLGA) microspheres was investigated. The terminal free carboxyl group of polymer was proved to be necessary for GM to be highly incorporated into microspheres by comparing interactions with GM and two types of polymers; free (ionized and non ionized) and the terminal esterified carboxyl group of polymer. The weight-average molecular weights (Mws) of component PLGAs of microspheres with an ionizable carboxyl group used here were approximately 4900 and 10000. The release pattern of GM was tested in phosphate buffered saline. The release rate of GM was dependent on the initial Mw and surface form. The GM release continued for 20 and 30 d from PLGA 4900- and PLGA10000-microspheres, respectively. The changes of total weight of microspheres tended to decrease with time, and the molecular weight distribution of PLGA gradually shifted to lower distribution, indicating a decrease in Mw. The changes and the shifts were dependent on the initial Mws of PLGAs but independent of their surface form. The half-times of wight loss of PLGA 4900- and PLGA10000-microspheres were about 10 and 20 d, respectively. From these results, the release profile of GM from PLGA microspheres was explained by the following three steps, i.e., 1) the release from the surface, 2) the relatively slow release caused by the obstruction of channels followed by the degradation of PLGA, 3) the release accompanied by the erosion of microspheres.

Biotransformation↗

Expression of granulocyte colony-stimulating factor and its receptor at the fetomaternal interface in murine and human pregnancy.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine which regulates proliferation and differentiation of neutrophilic granulocytes, and its receptor (G-CSF-R) is a member of the hemopoietic growth factor receptor family. We studied the expression of G-CSF and G-CSF-R at the fetomaternal interface in murine and human pregnancy. Immunohistochemical analysis and in situ hybridization indicated that both G-CSF and G-CSF-R are expressed in mouse spongiotrophoblasts and placental labyrinths, and human placental cytotrophoblasts and syncytiotrophoblasts. They were also detected in mouse decidual basalis cells and endometrial epithelial cells, and human decidual stromal cells and endometrial gland cells. These results suggest that G-CSF plays a role in decidual and placental functions by autocrine and paracrine mechanisms.

Abortion, Induced↗

Immunotoxins composed of monoclonal antibody to alpha-fetoprotein and gelonin as a potent hepatoma-targeted drug delivery system.

This study was carried out to evaluate our monoclonal antibody (MoAb) to alpha-fetoprotein (AFP), 80G, as a carrier for targeting AFP-producing hepatoma. Pharmacokinetic analysis showed that the MoAb 80G was actively incorporated into AFP-producing HuH-7N cells (xenograft of human hepatoma cell line, HuH-7) in nude mice. Four conjugates composed of MoAb 80G, and a type 1 ribosome-inactivating protein, gelonin, were prepared. They involve two disulfide-linked and two thioether-linked conjugates. The binding activity of conjugates against AFP remained as high as that of intact 80G according to enzyme-linked immunosorbent assay. The in vitro cytotoxic effects of all the conjugates were specific against AFP-producing HuH-7 cells. Of these conjugates, two containing gelonin modified with 2-iminothiolane were more potent than the others. They showed significant antitumor activity upon AFP-producing HuH-7N cells in nude mice. However, the disulfide conjugate was more toxic to mice than the thioether conjugate judging from the loss in body weight and the liver damage. These results suggest that our MoAb 80G is a suitable carrier for targeting AFP-producing hepatoma cells, and that the noncleavable thioether conjugate is promising as an AFP-producing hepatoma-targeted drug delivery system.

Animals↗

Effect of an angiotensin II receptor antagonist, TCV-116, on rat carotid artery neointimal formation after balloon injury.

Arterial injury by a balloon catheter produces marked smooth muscle cell proliferation and the participation of angiotensin II in this response has been suggested. In this study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV-116, on neointimal formation after rat carotid artery balloon injury. Oral administration of TCV-116 at doses of 1, 5 or 10 mg/kg/day significantly reduced the cross-sectional intimal area by 30%, 46% and 54%, respectively, and reduced the ratio of the intimal to medial cross-sectional areas by 23%, 41% and 50%. An angiotensin-converting enzyme inhibitor, lisinopril, had an effect similar to that of TCV-116. The effect of both drugs was significantly correlated with the reduction of both blood pressure and cardiac hypertrophy. We conclude that TCV-116 can prevent neointimal formation after balloon injury as well as reducing blood pressure and preventing cardiac hypertrophy.

Angiotensin Receptor Antagonists↗

Lectin electron microscopic histochemistry of the pseudoexfoliative material in the skin.

PURPOSE: To investigate the hypothesis that pseudoexfoliation (PSX) syndrome is a systemic disorder, the authors studied the composition of glycoconjugates in the intraocular and extraocular PSX material at the electron microscopic level, using a panel of lectins as cytochemical probes. METHODS: The authors examined 8 lid skins, 11 trabecular tissues, and 3 cataractous lenses from human eyes with PSX syndrome. Tissues were processed for electron microscopical histochemistry and stained with PNA, RCA120, DBA, SBA, ConA, WGA, UEA-I, and Lotus, with an indirect lectin-colloidal gold technique. RESULTS: Both the intraocular and extraocular PSX materials manifested almost identical reactivity to lectins, which indicated that glycoconjugates in the PSX material contained with sugar residues of galactose (PNA, RCA120), alpha-mannose (ConA), and N-acetyl-D-glucosamine (WGA). On the other hand, it was indicated that sugar residues of N-acetyl-D-galactosamine (DBA, SBA) and fucose (UEA-I, Lotus) were absent. Granular inclusions and microfibrils in the capsule and ocular zonules were stained similarly and weakly. CONCLUSIONS: The intraocular and extraocular PSX materials contained the same sugar residues of glycoconjugates, which suggested that those materials had the same nature. This study, the first documentation of lectin-binding sites on the extraocular PSX material, supported the hypothesis of PSX syndrome as a systemic disorder.

Exfoliation Syndrome↗

Secondary reconstruction for unfavorable microtia results utilizing temporoparietal and innominate fascia flaps.

Unfavorable results in reconstruction of the auricle for microtia can be encountered from time to time, in which secondary reconstruction of the auricle is usually performed. One must note that secondary reconstruction is much more difficult than primary reconstruction for the following reasons: (1) all necrotic skin and scar tissue from the primary reconstruction must be removed, thus limiting the surface area of the skin for the secondary reconstruction; (2) the presence of scar tissue and loss of tensility in the subdermal layer makes it difficult to construct a subcutaneous pocket for grafting of the three-dimensional costal cartilage framework; and (3) in patients with full-thickness skin grafts in the conchal and postauricular regions, contraction of the grafted skin was noted. In order to resolve these problems, the temporoparietal fascia flap was used in the first-stage three-dimensional frame grafting operation, and the innominate fascia flap, obtained from the same site as the temporoparietal fascia in the first-stage operation, was used for the second-stage operation. The retroauricular full-thickness skin graft was utilized for color match on the anterior surface of the auricle where it is visible, and substitute skin from the groin was used to cover the donor site. The procedures and results for secondary reconstruction for unfavorable microtia are presented in this article.

Adolescent↗

[Electron microscopic histochemical study in human trabecular meshwork--Second report: location of glycoconjugate residues using lectins].

The location of fourteen lectins in normal human trabecular meshworks were investigated with the electron microscope. The specimens were embedded in Lowicryl K4M at low temperature. Ultrathin sections were stained with biotin labeled lectins and colloidal gold labeled streptoavidin and observed with the electron microscope. ABA, ConA, DSA, PHA-E1, PHA-L4, WGA, LCA, and RCA120 were localized around fine fibrils underneath the endothelium of the trabecular wall of the Schlemm's canal (type I plaque) and collagenous fibers in the corneoscleral meshworks. ABA, ConA, and DSA were localized on the long-spacing collagens, basal membrane, microfibrils of elastic fiber (type II plaque), and fine granular (type III plaque). The present study indicated that extracellular matrices of normal human trabecular meshworks contained specific glycoconjugate residues.

Aged↗

Localization of elastin in the normal and glaucomatous human trabecular meshwork.

PURPOSE: The extracellular materials (ECMs) in the trabecular meshwork (TM) are thought to play a crucial role in aqueous outflow resistance. Immunohistochemical localization of elastin, one of the major ECMs in the normal and glaucomatous human TM, was examined ultrastructurally. METHODS: Eight normal eye bank eyes and 16 trabeculectomy specimens of primary open angle glaucoma (POAG, 11 eyes from 8 cases), congenital glaucoma (2 eyes from 1 case), and juvenile glaucoma (3 eyes from 2 cases) were embedded in Lowicryl K4M at low temperature. The distribution of elastin was studied by the protein A-gold technique. RESULTS: In normals, the gold particles indicating the antigenic sites for elastin existed mainly in the central amorphous element of the elastic-like fibers, and a few gold particles were observed within the area containing fine granular-like material and fine fibrillar-like material. No labeling was observed in cellular materials or other ECMs. In congenital and juvenile glaucoma, labeling was similar to that observed in normals. In POAG specimens compared to normals, there was an increased amount of elastin-bound immunogold particles along the inner canal endothelium. The increased gold particles, which did not have a fibrillar arrangement and were not enclosed by electron-dense microfibrils, were found within the area containing fine fibrillar-like material. However, labeling within the elastic-like fibers was similar to that observed in normals. CONCLUSIONS: Under electron microscopy, elastin could be localized in the normal and glaucomatous human TM. The results of this investigation suggest that elastin may play an important role in the etiology of POAG.

Adult↗

Determination of pyridonecarboxylic acids in plasma by reverse-phase high-performance liquid chromatography.

A simple qualitative and quantitative determination for pyridonecarboxylic acids including nalidixic acid (NA), oxolinic acid (OA) and pipemidic acid (PPA) in chicken plasma was carried out by microbiological, spectrophotometric, thin-layer chromatographic (TLC) and reverse-phase high-performance liquid chromatographic (HPLC) methods. As a test organism for bacteriological bioassay, Bacillus subtilis ATCC-6633 was the most sensitive of seven organisms investigated. Using the cup and the disc methods, a standard curve was obtained by determining the relationship between various drug concentrations and the diameter of the inhibition zone. The three drugs had two strong UV absorbance wavelengths (257 and 330 nm) on spectrophotometry. TLC analysis using a silica gel 60 F254 plate was investigated, and a solution of methanol:chloroform:acetic acid (3:1:1, v/v/v) was found to be the most suitable solvent for separation. The minimum concentration of drug detectable by this method was 0.5 microgram/ml for NA, 0.075 microgram/ml for OA and 0.39 microgram/ml for PPA. For HPLC analysis, a solution of acetonitrile:0.2 M phosphoric acid (1:1, v/v) was superior, and simultaneous determination of all three drugs was possible under the HPLC conditions used. The lowest measurable amount of drug in chicken plasma was 0.01 microgram/g. Recovery from extracts spiked with each drug at a known concentration was close to 100% for NA and OA, but only about 50% for PPA.

Animals↗