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R Yamasaki

Publications and source records attributed to R Yamasaki.

At least 37 records · Page 2Linked to original sources
PubMed1999

Novel small molecule nonpeptide aminopeptidase n inhibitors with a cyclic imide skeleton.

A novel series of small molecule nonpeptide aminopeptidase N (APN) inhibitors with a N-phenylphthalimide or N-phenylhomophthalimide skeleton were prepared. Evaluation of their protease inhibitory activities revealed that (i) some N-phenylphthalimide analogs are potent APN inhibitors, but they are also inhibitors of another protease, dipeptidylpeptidase IV (DPP-IV), and (ii) some N-phenylhomophthalimide analogs, including 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22), are potent and specific inhibitors of APN without DPP-IV-inhibitory activity. The structure-activity relationship studies of N-phenylphthalimides and N-phenylhomophthalimides are reviewed. PIQ-22 showed potent tumor-cell invasion-inhibitory activity.

Antineoplastic Agents↗
PubMed1999

[Usefulness of endovascular grafting for abdominal aortic aneurysm].

The purpose of this study was to determine the usefulness of endovascular grafting for abdominal aortic aneurysm (AAA) compared to conventional open repair. During the period from May 1998 through to April 1999, 16 patients (control group) with AAA underwent conventional open surgery and 6 patients (stent group) underwent endovascular grafting. Surgical data including operative time and intraoperative blood loss did not differ between the two groups. However, the postoperative parameters including the initiation of oral intake, the onset of flatus and the permission to walk were significantly sooner in the stent group than the control group. The postoperative changes of coagulopathy-fibrinolytic factor were comparable between the two groups. We conclude that the endovascular grafting is minimally invasive compared to conventional open surgery. In addition, there was no consumption coagulopathy in the endovascular grafting. However, it was necessary to develop new approach with new devices in order to perform endovascular grafting more safely.

Aged↗
PubMed1997

Immunoreactive growth hormone-releasing hormone (IR-GHRH) in the feto-placental circulation and differential effects of L-dopa, L-arginine and somatostatin-14 on the plasma levels of IR-GHRH in normal adults.

The relation of the physiological releases of growth hormone-releasing hormone (GHRH) and growth hormone (GH) into the circulation in various conditions was investigated using a sensitive and specific radioimmunoassay for plasma GHRH. The mean fasting plasma level of immunoreactive (IR)-GHRH in 72 normal adults was 10.3 +/- 0.5 (mean +/- SEM) pg/ml and there was no significant sex difference in the level. The concentrations of IR-GHRH in plasma from the umbilical artery and umbilical vein were 107.3 +/- 20.5 pg/ml and 33.6 +/- 3.8 pg/ml, respectively, and a marked arterio-venous gradient was observed in all 12 individuals examined. The plasma level of IR-GHRH in the maternal vein was significantly lower than that in the cord blood, but was similar to that in non-pregnant women. In normal adults, although there was no apparent fluctuation in the level of plasma IR-GHRH or of plasma GH during bed rest, a significant increase of plasma IR-GHRH was detected followed by, or synchronized with the surge of plasma GH after oral administration of L-dopa. In contrast, on L-arginine infusion, no proportional elevation of plasma IR-GHRH with increase in plasma GH was observed. During and after intravenous infusion of somatostatin, the circulating IR-GHRH level did not increase, but on stopping the infusion there was an immediate and marked rebound surge of GH. We conclude that 1) the elevated IR-GHRH in the cord blood plasma originates from the fetus and may have a primary role in enhancing secretion of GH which promotes growth in early human life, and 2) the participations of GHRH in the mechanisms of GH secretion seen after administrations of L-dopa, L-arginine and somatostatin are different.

Adult↗
PubMed1994

The structure of lipooligosaccharide produced by Neisseria gonorrhoeae, strain 15253, isolated from a patient with disseminated infection. Evidence for a new glycosylation pathway of the gonococcal lipooligosaccharide.

We studied the structure of the lipooligosaccharide (LOS) that is produced by Neisseria gonorrhoeae, strain 15253. This strain, recovered from a patient with disseminated infection, produces predominantly a single LOS component, and its oligosaccharide (OS) structure is different from those of previously studied LOSs. Definition of this OS structure provides additional information on the LOS biosynthesis. We determined that the 15253 OS has an unusual structure: 2 lactosyl residues at its nonreducing ends shown below, [formula: see text] where KDO is 2-keto-3-deoxy-mannooctulosonic acid and Hep is heptose. Comparison of this OS structure with those determined previously indicates the presence of a new glycosylation pathway for gonococcal OS biosynthesis: elongation of a GlcNAc-linked heptose, in contrast to elongation of the other heptose by sequential addition of glycoses which results in the antigenic similarity with human glycolipids. The current study provides not only additional structural information on LOS expressed during different clinical states of infection but also evidence for the diversity of gonococcal LOS biosynthesis. This evidence may be helpful in understanding the pathogenesis involving gonococcal LOS.

Acetylglucosamine↗
PubMed1994

Meningococcal group A lipooligosaccharides (LOS): preliminary structural studies and characterization of serotype-associated and conserved LOS epitopes.

Structural studies indicate that the neisserial lipooligosaccharides (LOS) are composed of an oligosaccharide (OS) portion with a phosphorylated diheptose (Hep) core attached to the toxic lipid A moiety. A conserved meningococcal LOS epitope, defined by monoclonal antibody (MAb) D6A, is expressed on group A and many group B and C meningococci of different LOS serotypes (J. J. Kim, R. E. Mandrell, H. Zhen, M. A. Apicella, J. T. Poolman, and J. M. Griffiss, Infect. Immun. 56:2631-2638, 1988). This MAb-defined D6A epitope is immunogenic in humans (M. M. Estabrook, R. E. Mandrell, M. A. Apicella, and J. M. Griffiss, Infect. Immun. 58:2204-2213, 1990; M. M. Estabrook, C. J. Baker, and J. M. Griffiss, J. Infect. Dis. 197:966-970, 1993). In this study, we characterize this important MAb-defined LOS epitope. Serotype L10 and L11 group A meningococal LOS were chemically modified and used to investigate what portion of the LOS molecule is important for expression of the conserved (D6A) epitope and serotype-associated LOS epitopes by use of immunoblotting techniques and selected MAbs as probes. Preliminary structural characterization of the LOS was also accomplished by electrospray ionization-mass spectrometry. Our results indicate the following. (i) Antibodies that recognize the serotype-associated or conserved LOS epitopes recognize the OS portion of the LOS. (ii) The phosphorylated diheptose core region of the OS is essential for expression of the conserved D6A epitope. (iii) The lipid portion of the molecule is important for optimum expression of the LOS epitopes. (iv) The proposed compositions of the O-deacylated LOS are consistent with the presence of a phosphorylated diheptose core and are as follows: for O-deacylated L10 LOS, 3Hex (hexose), 1HexNAc (N-acetylhexosamine), 2KDO (2-keto-3-deoxy-D-manno-octulosonic acid), 2Hep (heptose), 1PEA or 2PEA (phosphoethanolamine), and O-deacylated lipid A; and for O-deacylated L11 LOS, 2Hex, 1HexNAc, 2KDO, 2Hep, 2PEA, and O-deacylated lipid A. Because the phosphorylated diheptose core region of the LOS is essential for the formation of a conserved LOS epitope (D6A) that is immunogenic in humans, care should be taken to maintain stereochemical requirements for the expression of this conserved epitope in the design of effective, nontoxic LOS vaccines.

Animals↗
PubMed1994

Evaluation of the effects of various factors on the serum triglyceride level in young adults.

The life style of young adults has been receiving attention with a view to its improvement to preventing coronary heart diseases (CHD) in later life. In this study, for determining the influence of different life styles on the serum triglyceride level, we carried out surveys and laboratory studies on the relationships of the nutritional intake, physical activity, and cigarette smoking and alcohol consumption of young adults with their serum triglyceride levels. The nutritional survey indicated a significant correlation between the serum triglyceride level and carbohydrate intake (p < 0.01). In the survey of physical activity, a significant inverse correlation was found between the energy expenditure per kg body weight and the serum triglyceride level (p < 0.05). No significant relationship was found of smoking or drinking with the serum triglyceride level. The body mass index was found to have effects on both the serum triglyceride and total cholesterol levels. Of the factors examined, carbohydrate intake and energy expenditure per kg body weight had the greatest effects on the serum triglyceride level. Considering the trend for young people to consume large quantities of carbonated drinks, in which most of carbohydrate is sucrose, we tested the affect of a high carbohydrate diet on one group of subjects and found that it caused a significant increase in the serum triglyceride level (p < 0.05). Another group for whom a mild exercise regimen was prescribed showed slight, but not significant decrease in the serum triglyceride level. These results suggest that at least optimal nutrition and physical activity including weight control during adolescence are important for preventing CHD.

Adult↗
PubMed1993

Inhibition of platelet binding and aggregation by streptococcal exopolysaccharide.

Streptococcal exopolysaccharides are major virulence factors in the pathogenesis of endocarditis. They promote bacterial adherence to valves and subsequent vegetation formation. Since platelet binding and aggregation by streptococci are postulated mechanisms for endocardial colonization and vegetation production, the effect of exopolysaccharide on binding and aggregation was evaluated by flow cytometry and aggregometry. Streptococcus salivarius D1, a minimal exopolysaccharide producer, bound human platelets extensively (86.8% of bacteria bound by 1 min). S. Salivarius M13 and M15 and Streptococcus mitis M4 produced larger amounts of exopolysaccharide and bound platelets significantly less (52.6%, 51.2%, 52.8%, respectively). Exopolysaccharide also inhibited platelet aggregation: Strains with minimal exopolysaccharide aggregated platelets maximally, while strains with extensive exopolysaccharide failed to induce aggregation. Removal of exopolysaccharide by shearing restored aggregation by these latter strains. Thus, exopolysaccharides can inhibit the binding and aggregation of platelets by streptococci. The virulence associated with exopolysaccharide may result from the inhibition of platelet-mediated interactions that limit disease progression.

Blood Platelets↗
PubMed1993

Demonstration of biological activity of a growth hormone-releasing hormone-like substance produced by a pheochromocytoma.

The biological characteristics of a growth hormone-releasing hormone (GHRH)-like substance produced by a pheochromocytoma were studied. Analysis by gel filtration chromatography combined with the use of two distinct GHRH antisera that recognize the N- and C-termini of authentic GHRH(1-44)NH2 indicated molecular heterogeneity of the immunoreactive GHRH in the tumor extract, but a component corresponding to GHRH(1-44)NH2 was the predominant form. The biological activity of this immunoreactive component was assessed in vitro by measuring its ability to induce growth hormone release from dispersed rat anterior pituitary cells. At concentrations of 0.125-2.0 nmol/l, the test materials induced a dose-related increase in growth hormone release from the cells into the incubation medium (range 992 +/- 68-1872 +/- 32 ng.1.7 x 10(5) cells-1 x 3 h-1), similar to that observed with synthetic GHRH(1-44)NH2. (control value 640 +/- 30 ng.1.7 x 10(5) cells-1 x 3 h-1). This suggests that immunoreactive GHRH in the tumor has almost the same biological activity as the synthetic product and that a combination of pheochromocytoma and acromegaly is not always fortuitous because both diseases may be caused by a single neoplasm.

Adrenal Gland Neoplasms↗
PubMed1992

Structural analysis of lipooligosaccharide produced by Neisseria gonorrhoeae, strain MS11mk (variant A): a precursor for a gonococcal lipooligosaccharide associated with virulence.

We studied the structure of the lipooligosaccharide (LOS) that is produced by a variant A of strain MS11mk. This variant produces a single LOS that is recognized by monoclonal antibody (MAb) 2-1-L8. In a recent study of the pathogenesis of Neisseria gonorrhoeae in male volunteers, variant A gave rise to other phase variants that produce higher molecular weight LOSs, and these LOS were associated with virulence. Definition of the structure of the variant A LOS is important to understand the biosynthesis of LOS and its expression in vivo. The dephosphorylated oligosaccharide (OS) structure derived from the variant A LOS was analyzed by two-dimensional NMR and methylation analysis. The OS structure was found to be a truncated form of the LOS produced by strain F62 [Yamasaki et al. (1991) Biochemistry 30, 10566-10575]; the variant A OS is a hexamer, a beta-lactosyl residue linked to a tetrasaccharide: Gal beta 1-->4Glc beta 1-->4[GlcNAc alpha 1-->2Hep alpha 1-->3]Hep alpha 1-->KDO. We determined that the variant A LOS is a precursor for the synthesis of higher MW LOS. We also studied expression of the MAb 2-1-L8-defined epitope present on the variant A LOS. Our data indicate that the MAb-defined epitope is not a linear beta-lactosyl residue but its specificity is directed toward the phosphorylated GlcNAc-Hep-Hep residue. Since this MAb binds to gonococci, at least part of the phosphorylated diheptose area is exposed on the gonococcal surface.

Antibodies, Monoclonal↗
PubMed1992

Ability of gonococcal and meningococcal lipooligosaccharides to clot Limulus amebocyte lysate.

We investigated whether the striking difference in severity of coagulopathy observed between bacterial sepsis involving Neisseria meningitidis and Neisseria gonorrhoeae species is related to species-dependent abilities to directly activate coagulation. Using lipooligosaccharide (LOS)-activated gelation of Limulus amebocyte lysate, we compared the relative abilities of outer membrane LOS of 10 N. meningitidis and 10 N. gonorrhoeae strains to initiate coagulation. A wide range of procoagulant potencies was observed for each species, and there was significant overlap of potencies between species. Relative biological activities did not correlate with the oligosaccharide components as defined by LOS molecular weight or specific antigenic epitopes. Purified lipid A of two LOS strains of different potency demonstrated relative procoagulant biological activities similar to those of their parent LOSs. When these lipid A preparations were further separated by thin-layer chromatography, the most polar component of each lipid A possessed the majority of the procoagulant activity. We concluded that the ability of neisserial LOS to initiate coagulation of Limulus lysate is a property of the lipid A portion of the molecule and is most likely determined by fine structural differences in the lipid A which are independent of species.

Animals↗
PubMed1992

Lipooligosaccharides (LOS) of some Haemophilus species mimic human glycosphingolipids, and some LOS are sialylated.

The lipooligosaccharides (LOS) of strains of Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitidis, and Neisseria lactamica contain epitopes that are antigenically and structurally similar to carbohydrates present in human glycosphingolipids. LOS from strains of Haemophilus influenzae and H. influenzae biogroup aegyptius were tested for the binding of monoclonal antibodies (MAbs) that bind to human glycosphingolipids possessing Gal beta 1-4GlcNAc (MAb 3F11) and Gal alpha 1-4Gal beta 1-4Glc (MAb anti-Pk). In solid-phase radioimmunoassays, the LOS of 18 of 19 H. influenzae type b (Hib), 8 of 19 nontypeable H. influenzae, and 10 of 20 H. influenzae biogroup aegyptius strains bound MAb anti-Pk. The LOS of 13 of 19 Hib, 10 of 16 nontypeable H. influenzae, and 2 of 18 H. influenzae biogroup aegyptius strains bound MAb 3F11. Neuraminidase treatment of the strains increased the binding of MAb 3F11 by more than twofold in 47% of the H. influenzae strains, suggesting that sialic acid occluded the LOS structure recognized by MAb 3F11. The material released from neuraminidase-treated Hib LOS was confirmed to be sialic acid by high-performance anion-exchange chromatography. A recombinant plasmid containing genes involved in Hib LOS biosynthesis directed the expression (assembly) of the 3F11 epitope in Escherichia coli. These studies demonstrate that H. influenzae and H. influenzae biogroup aegyptius express at least two LOS epitopes that are similar to those present in human glycosphingolipids. Sialic acid was present on the LOS of some H. influenzae strains and prevented the binding of MAb 3F11 to its epitope. The oligosaccharide portion of sialylated LOS may also resemble sialylated oligosaccharides present in human glycosphingolipids (gangliosides).

Antibodies, Monoclonal↗
PubMed1992

Differences in pathological findings and growth hormone responses in patients with growth hormone-producing pituitary adenoma.

Plasma growth hormone (GH) responses to various stimuli were examined in 21 patients with GH-producing pituitary adenomas, classified into three types by the immunohistochemistry of cytokeratin and the glycoprotein hormone alpha-subunit distribution. Seven type 1 adenomas were exclusively composed of cells in which the cytokeratin formed a dot-like pattern; they were chromophobic to hematoxylin and eosin (H&E), occasionally positive for GH, and almost completely negative for the alpha-subunit. Thirteen type 2 adenomas were composed of cells with cytokeratin that had a perinuclear distribution; they were eosinophilic to H&E, and diffusely positive for both GH and the alpha-subunit. One patient had a type 3 adenoma which had a mixed pattern of intracellular cytokeratin distribution and was chromophobic and eosinophilic to H&E. Clinically, type 1 is characterized by earlier onset, larger tumor size, and more frequent aggressive extension. Paradoxical GH responses to TRH and OGTT were seen in 1 of 6 patients (16.7%) of type 1 and 8 of 9 patients (88.9%) of type 2, and 0% of type 1 and 62.5% of type 2, respectively. Type 2 cases showed higher plasma GH response to GH-releasing hormone, and a tendency to greater suppression of plasma GH by bromocriptine compared with type 1. Octreotide acetate administration revealed that the nadir/basal ratio of plasma GH levels was 42.9 +/- 6.6% in type 1 and 13.5 +/- 5.8% in type 2. These results suggest that there is a pathophysiological difference between these two distinct types of GH-producing pituitary adenomas.

Adenoma↗
PubMed1992

Mechanism of impaired growth hormone secretion in patients with Cushing's disease.

The function of the growth hormone-releasing hormone (GHRH)-growth hormone (GH) axis in Cushing's disease was studied by monitoring (a) the GH responses to GHRH loading and L-dopa loading, (b) the GHRH response to L-dopa loading, and (c) the daytime profiles of plasma GH concentration. GH release following GHRH and L-dopa was blunted in patients as compared to that in age-matched control subjects. However, GHRH release following L-dopa was similar in patients and controls. The plasma GH levels in four patients measured every 20 min by a highly sensitive immunoradiometric assay for GH showed pulsatile GH secretion at low levels during the observation period. These results indicate that GHRH release from the hypothalamus is preserved in patients with Cushing's disease, and support the hypothesis that glucocorticoid inhibits GH secretion by altering the hypothalamic somatostatin tone.

Adult↗
PubMed1991

Radioimmunoassay of growth hormone-releasing hormone (GHRH) with a polyclonal antibody against synthetic GHRH(1-29)-Gly4-Cys-NH2: method and clinical studies.

A radioimmunoassay (RIA) for growth hormone-releasing hormone (GHRH) using a polyclonal antibody against synthetic GHRH(1-29)-Gly4-Cys-NH2 has been developed. The antiserum (RBM105) showed full cross-reactivity with GHRH-(1-44)NH2, GHRH-(1-40)OH, GHRH-(1-37)OH and GHRH-(3-44)NH2, and probably recognized the region of Ala4 to Lys12 of GHRH. Since the sensitivity of the GHRH RIA was 1.5 pg/tube, the lowest detectable plasma level was 5 ng/l when an extract of 0.3 ml of plasma per tube was used. On gelfiltration chromatography, the GHRH immunoreactivity of normal plasma was eluted in the same position as synthetic GHRH. The plasma GHRH concentration in healthy subjects was 20.5 +/- 6.5 ng/l (mean +/- SD), and in patients with hypothalamic disorders was 17.4 +/- 2.0 ng/l. In contrast, the plasma GHRH level in hemodialysis-dependent, chronic renal failure (CRF-HD) patients (38.7 +/- 13.1 ng/l) was significantly higher than normal. The acromegalic patients were 24.3 +/- 11.9 ng/l, except for one patient with ectopic GHRH syndrome (990 ng/l): his plasma GHRH level reached 7,100 ng/l during operation, and then decreased logarithmically to 70 ng/l after 6 h. Somatostatin at concentrations of 10 and 1,000 nmol/l significantly suppressed (GHRH release) from primary culture cells of the GHRH-producing tumor from 17.3 +/- 0.92 ng/2 x 10(5) cells to 9.98 +/- 3.61 and 4.32 +/- 1.01 ng/2 x 10(5) cells, respectively after 48 h. These data indicate that this GHRH RIA is useful for determining the plasma GHRH concentration in normal and diseased states and also for in vitro studies of GHRH release.

Acromegaly↗
PubMed1991

Structural determination of oligosaccharides derived from lipooligosaccharide of Neisseria gonorrhoeae F62 by chemical, enzymatic, and two-dimensional NMR methods.

F62 LOS of Neisseria gonorrhoeae consists of two major LOS components; the higher and smaller molecular weight (MW) components were recognized by MAbs 1-1-M and 3F11 respectively. Base-line separation of the two major oligosaccharide (OS) components from F62 LOS was achieved by Bio-Gel P-4 chromatography after dephosphorylation of the OS mixture. The structures of the two major OSs were studied by chemical, enzymatic, and 2D NMR methods [double quantum filtered COSY (DQF-COSY), delayed COSY (D-COSY), homonuclear Hartmann-Hahn spectroscopy (HOHAHA), pure-absorption 2D NOE NMR] as well as methylation followed by GC/MS analysis. The OS component derived from the MAb 1-1-M defined LOS component was determined to have a V3-(beta-N-acetylgalactosaminyl)neolactotetraose structure (GalNAc is beta 1----3-linked to a neolactotetraose) at one of its nonreducing termini as shown below. The above pentaose is linked to a branched diheptose-KDO core in which a GlcNAc is alpha-linked. The OS component derived from the MAb 3F11 defined LOS component did not have a GalNAc residue. The rest of its structure was identical to that of the OS-1, and a neolactotetraose is exposed at its nonreducing terminus. [formula: see text]

Antigens, Bacterial↗
PubMed1991

Radioimmunoassay for activin A/EDF. Method and measurement of immunoreactive activin A/EDF levels in various biological materials.

A radioimmunoassay (RIA) for the measurement of activin A, which is identical to erythroid differentiation factor (EDF), has been developed. A specific antiserum against activin A/EDF was raised in rabbits using a mixture of recombinant EDF and polyvinyl pyrrolidone. Of the compounds tested this polyclonal antibody cross-reacted only with bovine inhibin (3.2%) and human TGF-beta (4.2%). The least detectable value in this assay was 0.06 ng/tube. The within- and between-assay coefficients of variation at three different concentrations were 3.6-9.8% and 3.4-7.7%, respectively. Using this RIA, immunoreactive activin A/EDF levels in various biological fluids and tissues were examined. The dose-response curves of porcine follicular fluid and ovarian extract were parallel to the standard curve, and porcine follicular fluid contained high activin A/EDF immunoreactivity (1050 ng/ml). On gel chromatography of porcine follicular fluid, the major immunoreactivity was eluted in the same position as authentic activin A/EDF. Human placental extract and amniotic fluid had relatively high immunoreactive activin A/EDF levels (174 ng/g wet wt. and 63.9 ng/ml, respectively), but the dose-response curve of amniotic fluid was not parallel to the standard curve. Among rat tissues, the ovary showed the highest activin A/EDF immunoreactivity (163 ng/g wet wt.) much lower than that of porcine ovary (1020 ng/g wet wt.). Low immunoreactive activin A/EDF levels were detected in most parts of rat brain (8.7-14.2 ng/g wet wt.), except for the pituitary gland (70.0 ng/g wet wt.). The initial plasma half clearance time (t1/2) of exogenous activin A/EDF was 14 min in the rat and the plasma FSH concentration did not change significantly during this period. These results suggest that this RIA system has sufficient sensitivity and specificity to measure activin A/EDF concentrations in biological materials, and that the reproductive tissues are the main sources of activin A/EDF.

Activins↗