Biomedical subjects

Y Yamamura

Publications and source records attributed to Y Yamamura.

At least 199 records · Page 11Linked to original sources

PubMed1994

Effects of vasopressin V1 and V2 receptor antagonists on progressive renal failure in rats.

1. The relationship between vasopressin and the progression of renal failure has been proposed, but not intensively investigated because of a lack of orally available, selective vasopressin antagonists. 2. The effects of novel, orally available vasopressin V1 and V2 receptor antagonists on several indices of the progression of chronic renal failure, i.e. blood pressure, urinary protein excretion, sodium balance and renal histopathology, were investigated by using Wistar rats with adriamycin-induced nephropathy accelerated by deoxycorticosterone acetate-salt hypertension. Groups 2 and 3 were treated with V1 and V2 antagonists, respectively, while the untreated group 1 served as the control. To block the effects of vasopressin efficaciously, V1 and V2 antagonists were simultaneously administered (group 4). 3. At week 6, 2 weeks after the beginning of administration of deoxycorticosterone acetate-salt and vasopressin antagonists after the second injection of adriamycin, V1 and V2 antagonists given either alone or in combination significantly reduced the systolic blood pressure as compared with the control, and urine volume was increased in groups 3 and 4. The proteinuria was also decreased at week 10 in groups 2, 3 and 4. Differences in sodium excretion between all groups were not significant. Histopathological alterations in the kidneys of group 4 were significantly ameliorated. 4. These results suggest that a combination of V1 and V2 antagonists can have therapeutic effects in certain types of chronic renal failure.

Animals↗

PubMed1994

Effects of oral AVP receptor antagonists OPC-21268 and OPC-31260 on congestive heart failure in conscious dogs.

Rapid right ventricular pacing could induce congestive heart failure in conscious dogs with significant increase in plasma concentration of arginine vasopressin (AVP) (from 1.2 +/- 0.2 to 3.4 +/- 0.6 pg/ml). In this experimental model of heart failure, oral administration of the selective AVP V1 receptor antagonist OPC-21268 significantly increased cardiac output and improved renal function without significant changes in serum electrolytes and hormones. Oral administration of the selective AVP V2 receptor antagonist OPC-31260 induced marked water diuresis, which resulted in significant increases in serum sodium concentration, plasma renin activity, and plasma concentration of AVP, although it did not produce hemodynamic improvement. Combined administration of OPC-21268 and OPC-31260 showed supra-additive hemodynamic responses as well as additive renal and metabolic responses, i.e., it showed prolonged decrease in mean arterial pressure and profound increase in cardiac output. These results suggest that AVP plays a significant role in elevation of vascular tone through V1 receptors and plays a major role in retaining free water through V2 receptors in this model of heart failure. Furthermore, combined administration of V1 and V2 receptor antagonists could induce not only metabolic and hormonal responses but also more beneficial hemodynamic responses than those observed following treatment with V1 receptor antagonist alone.

Animals↗

PubMed1994

Chronic and selective vasopressin blockade in spontaneously hypertensive rats.

Chronic effects of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on conscious spontaneously hypertensive rats (SHR) were investigated. SHR and Wistar rats were divided into four groups, groups S-1 to S-4 and W-1 to W-4, respectively. Groups S-1 and W-1 were untreated as control. Groups S-2 and W-2 were treated with V1 antagonist, groups S-3 and W-3 received V2 antagonist, and groups S-4 and W-4 were treated with both of V1 and V2 antagonists. V1 and/or V2 antagonists did not affect degree of blood pressure of W-2, W-3, and W-4 rats, and V1 antagonist, alone or combined with V2 antagonist, slightly reduced increases in blood pressure of S-2 and S-4 rats without significance. However, V2 antagonist induced significantly massive and hyposmolar urine in W-3 rats compared with that in S-3 rats. In conclusion, in SHR, circulating vasopressin contributes to increases in blood pressure via either V1 or V2 receptors less than expected from previous studies with antibodies or peptide antagonists.

Animals↗

PubMed1994

Organic osmolytes in rat renal inner medulla are modulated by vasopressin V1 and/or V2 antagonists.

For the purpose of clarifying the role of vasopressin V1 and V2 receptors in osmolyte accumulation, we determined the effects on the inner medullary osmolyte content of the administration of orally active vasopressin V1 and/or V2 receptor antagonists OPC-21268 (i.e., 1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl)- 3,4-dihydro-2(1H)-quinolinone) and OPC-31260 (i.e., 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tet rah ydro-1H- benzazepine] under a condition of maximal urine concentration achieved by water deprivation for 4 days. Taurine content increased significantly with the use of the V2 antagonist, irrespective of the use of the V1 antagonist. Inner medullary betaine content decreased with the administration of the V1 antagonist, irrespective of the administration of V2 antagonist. The administration of either the V1 or V2 antagonist alone did not affect sorbitol content, aldose reductase activity, or aldose reductase mRNA abundance in renal inner medulla. However, the combined administration of the V1 and V2 antagonists decreased all of these significantly. Myo-inositol content was not affected by the administration of the V1 or V2 antagonists. Glycerophosphorylcholine content was decreased with the use of the V2 antagonist, irrespective of the use of the V1 antagonist, and this effect paralleled urine osmolality. In conclusion, the individual organic osmolytes responded differently to the antagonists of vasopressin V1 and/or V2 receptors. The mechanisms linked to vasopressin V1 and/or V2 receptors appeared to modulate the accumulation of some organic osmolytes in the inner medulla. Aldose reductase mRNA abundance and sorbitol accumulation in the inner medulla appeared to be mediated through either V1 or V2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗

PubMed1994

Expression of neural cell adhesion molecule in normal gastric mucosa and in gastric carcinoid tumors.

Expression of neural cell adhesion molecule (NCAM) in the digestive system was studied with NE-150 monoclonal antibody, together with those against Lewis blood group antigens. NE-150 did not react with any of 32 cell lines tested derived from digestive tract cancers. In gastric adenocarcinomas NCAM was not expressed regardless of its differentiation status, while in gastric carcinoids and in other carcinoid tumors of different organs, it was present in all the specimens tested. Among normal tissues, it reacted with the deep gastric gland and the islets of Langerhans. These results suggest that NCAM is one of the most specific markers for gastric carcinoid tumors. It was also suggested that the gastric carcinoid tumor might be derived from NCAM-positive cells in the deep gastric gland. These findings should be exploitable in subgrouping gastric tumors in terms of antigen expression.

Adenocarcinoma↗

PubMed1994

OPC-21268, a vasopressin V1 antagonist, produces hypotension in spontaneously hypertensive rats.

We studied the hypotensive effects of OPC-21268, an orally effective nonpeptide vasopressin V1 receptor antagonist, in spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP). OPC-21268 was given intravenously to conscious, freely moving SHR and SHRSP. We used young and aged animals to examine the contribution of vasopressin to the development and maintenance of hypertension in both types of rats. In SHR, hypertension was fully established at 38 weeks of age, and intravenous injection of OPC-21268 produced slight hypotensive effects at either 38 or 70 weeks of age. In SHRSP, hypertension developed at 25 weeks of age, and blood pressure was sustained at a high level (approximately 250 mm Hg systolic blood pressure) thereafter. Intravenous administration of OPC-21268 did not cause hypotensive effects in young rats at 15 weeks, but at 25 weeks a significant decrease in blood pressure was observed. Furthermore, in the malignant state of SHRSP (35 to 41 weeks), OPC-21268 significantly decreased mean blood pressure by 32.4 +/- 7.9 mm Hg (mean +/- SEM) at 3 mg/kg IV, and the decrease was dose dependent (0.3 to 3.0 mg/kg). Plasma vasopressin concentrations were increased in a more malignant phase of SHRSP at 45 weeks of age, whereas at other ages of SHRSP or in SHR, plasma vasopressin levels were not increased. These results suggest that vasopressin plays an important role through V1 receptors in the maintenance of hypertension, at least in the malignant phase of SHRSP, and OPC-21268 may be therapeutically useful in the treatment of some types of hypertension.

Animals↗

PubMed1994

Background levels of total mercury concentrations in blood and urine.

We investigated the background levels of total mercury in blood and urine samples from Japanese subjects without occupational exposure to mercury vapor. Blood and urine specimens were decomposed in sealed Teflon containers, and total mercury concentration was measured by reductive vaporization-gold amalgam capture-atomic absorption spectrophotometry. The mean total mercury concentration in the blood of 56 women aged 34-65 was 18.2 +/- 9.9 ng/ml (range 3.9-56.8 ng/ml). The mean total mercury concentration in the urine of 130 men aged 22-39 was 2.33 +/- 1.50 micrograms/l (range 0.27-10.26 micrograms/l). The mean total mercury concentration in urine adjusted by specific gravity was 2.19 +/- 1.15 micrograms/l (range 0.68-7.68 micrograms/l), and that adjusted by creatinine was 1.51 +/- 0.68 micrograms/g creatinine (range 0.39-4.21 micrograms/g creatinine). These concentrations did not differ greatly from those reported from Europe and Japan. In expressing the total mercury concentration in urine, the creatinine-adjusted range between the minimum and maximum values was smaller than the range adjusted by specific gravity.

Adult↗

PubMed1994

Blood and urinary levels of metals (Pb, Cr, Cd, Mn, Sb, Co and Cu) in cloisonne workers.

Blood and urine samples from cloisonne ware workers were assayed for Pb, Cr, Cd, Mn, Sb, Co and Cu for biological monitoring. Mean blood Pb levels were 47.8 +/- 27.3 micrograms/dl (111-13.3 micrograms/dl) for 49 cloisonne glaze workers, and 0.97 +/- 0.47 microgram/dl (2.4-0.6 microgram/dl) for 62 normal subjects. There was a distinct difference between the 2 groups, and slight differences (p < 0.01) in mean Cr, Cd and Mn levels. There was a distinct difference in mean urinary Pb level between the 2 groups, and slight differences (p < 0.01) in mean Cr, Cd and Mn levels. The correlation coefficient, r, between blood Pb and Cd levels was 0.631 (p < 0.01) for 132 subjects consisting of cloisonne ware workers and normal subjects. r between blood Pb and blood Cr levels was 0.501 (p < 0.01), and that between blood and urinary Pb levels, 0.794 (p < 0.01). The above assays showed that glaze workers at cloisonne plants suffer severe exposure to lead and slight exposure to Cd and Cr.

Antimony↗

PubMed1994

[The effect of age and disease on the MR imaging T2 low signal intensity area in the cerebral cortex].

We retrospectively studied magnetic resonance (MR) images of the brain in 139 patients (16 cases of Alzheimer's disease, 8 cases of Parkinson's disease, 53 cases of multiple cerebral infarct, 33 cases of other central nervous diseases, and 29 cases of peripheral neuropathy) between the age of 6 and 85 years old with a mean age of 60.6 +/- 18.5 to examine the appearance of T2 low signal intensity areas (T2CLIA) in the cerebral cortex. Motor, occipital, sensory or other cortices were evaluated with long repetition time/echo time (TR/TE) spin-echo sequences and staged into three grades in the motor cortex: none, partial, and whole; and two grades in the others: none or present. In general, T2CLIA was not seen in any cortex in patients less than 50 years old, then after 50 years old T2CLIA increased with age. Over 70 years of age T2CLIA appeared in 50.9% of patients in the whole motor cortex, 88.7% in either whole or partial motor cortex, 47.2% in the occipital cortex, and 20.8% in the sensory cortex. T2CLIA was not observed in other cortices. The incidence of T2CLIA appearance in the motor cortex was significantly higher in all central nervous diseases than in cases of peripheral neuropathy over 70. T2-CLIA showed a correlation with temporal lobe atrophy and white matter lesions in the motor cortex. In the sensory cortex, T2CLIA correlated with white matter lesions. These results suggest that T2-CLIA may correlate with age or accumulation of nonheme iron in the cortex associated with central nervous diseases.

Adolescent↗

PubMed1994

[A case of idiopathic superficial siderosis of the central nervous system].

A 59-year-old man developed a staggering and wide based-gait in July 1990. Dysarthria, hearing loss, vexation and disturbance of memory appeared in January 1991. He consulted our clinic in May 1991, and cerebellar ataxia, neurogenic bladder, and cerebellar atrophy on brain CT were noted. Subsequently, he was followed as OPCA. Brain and spinal cord MRI (T2 and proton weighted images) revealed hypointensity on the surface of the Sylvian fissure, cerebellum, brainstem and spinal cord. We diagnosed this case as superficial siderosis because of the clinical course, i.e. cerebellar ataxia, dementia and sensorineural hearing impairment, and specific findings on MRI. We consider this case idiopathic superficial siderosis because the origin of the bleeding source was unknown. IMP-SPECT showed low perfusion in the cerebellum and frontal lobe where hemosiderin was heavily deposited. RI cisternography revealed a disturbance of CSF absorption even after 48 hours. The basic rhythm on EEG was slow alpha band with sporadic theta waves dominantly in the frontal lobe. His central conduction time on ABR and SEP was delayed, OKN was poorly elicited and ETT exhibited a staircase pattern. The physiological results as well as the clinical manifestations of the present case suggest that hemosiderin deposit on the surface of brain and spinal cord caused serious damage to the underlying structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Diseases↗

PubMed1994

Proliferative response of CD4+ and CD8+ T cell subsets from Hispanics with HIV+ and AIDS: the superantigen hypothesis.

It has been hypothesized that the progressive deletion of CD4+ T cells in the course of infection due to human immunodeficiency virus (HIV) may be mediated in part by interaction with a superantigen inherent in an HIV protein. Consequently, selective loss of CD4+ cells with a T cell receptor V beta-chain capable of interaction with superantigen would produce a CD4+ population less or totally unresponsive to superantigen such as staphylococcal enterotoxins B and A (SEB and SEA respectively), but not to other mitogens such as concanavalin A, anti-CD3 (OKT3), or pokeweed mitogen. We tested this hypothesis by comparing the proliferative response of SEB and SEA with the other mitogens for 25 controls, 20 HIV+, and 15 donors with acquired immune deficiency syndrome (AIDS). We found that peripheral blood mononuclear cells, as well as the CD4+ and CD8+ subsets from both HIV+ and AIDS sources, the degree of suppression of mitogenesis for SEB and SEA was approximately equal to or less than that of the other mitogens. Moreover, suppression of HIV+ CD4+ and CD8+ T cell responses to SEB and SEA was equal (26%). If HIV superantigens exist, our data suggest that they are not responsible for the selective depletion of the CD4+ T cell subset as evaluated by SEB and SEA specificity.

Acquired Immunodeficiency Syndrome↗

PubMed1994

[Amount of mercury from dental amalgam filling released into the atmosphere by cremation].

Mercury in dental amalgam filling is released into the atmosphere by cremation and is a suspected source of mercury pollution. The amount of mercury released was measured at three crematoriums. First, mercury levels in the atmosphere were measured. Mercury existed mainly in the gaseous form in ambient air. The concentration of atmospheric mercury at the three crematoriums (S, T and M) ranged from 4.3 to 19.7ng/m3, which was nearly identical to levels in our university surveyed as the control area and also to the levels of atmospheric mercury in general in Japan. Secondly, the amount of mercury release from T crematorium was estimated using official published statistical data in Japan and calculated as follows: sigma[(age specific number of dead that were cremated) x (the number of restored teeth by age category) x (mercury content per amalgam filling (0.6 g))] x (prevalence rate of restoration with amalgam). The amount of mercury released from this crematorium was estimated to be approximately 9.4 kg per year, or a daily release of 26 g into the ambient air. These results indicate that mercury release by cremation is similar to that from other man-made sources.

Air Pollutants↗

PubMed1994

[Antiplatelet therapy in patients with cerebral thrombosis at the chronic phase--assessment of its effect on coagulation and fibrinolytic parameters].

We studied the effect of antiplatelet therapy not only on the secondary prevention of stroke but also on the suppression of vascular damages in patients with cerebral thrombosis at the chronic phase. We measured von Willebrand factor (vWF) as a marker for the endothelial system, and coagulation and fibrinolytic parameters in addition to platelet functions. The platelet aggregation and markers for platelet activation were monitored for the adequate inhibition of platelets. Twenty-one patients were treated with 200 mg ticlopidine. 9 patients with 100 mg ticlopidine and 60-150 mg acetylsalicylic acid, and 18 patients with 200 mg cilostazol daily. The mean duration of follow up was 8.4 +/- 3.0 months. A patient was attacked by a recurrent stroke, but no fatal vascular events occurred during the period. A significant decrease was observed in the collagen- and ADP-induced platelet aggregation and markers for platelet activation such as platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) by the antiplatelet therapy. In addition, the activities of coagulation factor VIII (FVIII) and vWF, markers for vascular damages, showed a significant decrease. The results suggest that the antiplatelet therapy could ameliorate the vascular damage through the inhibition of platelet function. Moreover, thrombin-antithrombin III complex (TAT) and alpha 2-plasmin inhibitor-plasmin complex (PIC), markers for the activation of coagulation and fibrinolytic systems, decreased significantly, suggesting that the treatment inhibits the activation of coagulation and fibrinolytic systems induced by the platelet activation. The activities of FVIII and vWF decreased significantly when the level of beta TG or that of PF4 lowered sufficiently by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Erythropoietin receptor and interleukin-2 receptor use different downstream signaling pathways for proliferation and apoptosis-block.

Erythropoietin (EPO) regulates proliferation and differentiation and prevents apoptosis of erythroid progenitor cells by binding to erythropoietin receptor (EPOR) expressed on the surface of those cells. The mechanism by which EPO signal is transmitted to the cells through EPOR is still unclear. In the present study, we introduced and expressed EPOR in an interleukin-3 (IL-3) dependent pro-B cell line, BAF-B03 and an interleukin-2 (IL-2)-dependent cytotoxic T cell line, CTLL-2 and analyzed their growth response to EPO and the DNA breakdown characteristic to apoptosis after deprivation of the growth factor. BAF-B03-derived cells expressing EPOR proliferated in response to EPO but CTLL-2-derived cells expressing EPOR (C/EPOR) did not. DNA from C/EPOR cells cultured in the absence of IL-2 with or without EPO had similar patterns of DNA breakdown. These results suggest that downstream signaling pathways for the cell proliferation and apoptosis-block are, at least, partially different between EPOR and IL-2 receptor (IL-2R).

Animals↗

PubMed1993

Orally active, nonpeptide vasopressin V1 antagonists. A novel series of 1-(1-substituted 4-piperidyl)-3,4-dihdyro-2(1H)-quinolinone.

A series of compounds has been synthesized and demonstrated to be antagonists of V1 receptors both in vitro and in vivo. These compounds are structurally related to the 1-(4-piperidyl)-2(1H)-quinolinones, including OPC-21268, an orally bioavailable AVP V1 antagonist with high V1 specificity. It has been found that the introduction of an acetamide group on the terminal alkoxy chain of 41-44 leads to an increase in oral activity. Certain of these compounds may have efficacy in the study of AVP V1 receptors.

Administration, Oral↗

PubMed1993

Characterization of gastrin/CCK receptors on gastric carcinoid tumor membrane of Mastomys natalensis.

Recently, we identified the specific binding site for gastrin on the gastric carcinoid tumor of Mastomys (Praomys) natalensis. In this study, precise characterization of the gastrin binding site on these tumors was performed. Both 125I-human gastrin I (gastrin) and 125I-CCK-8 bound specifically to the cell membrane, and Scatchard analysis revealed a high affinity binding site for each ligand with similar Kd and Bmax values. The specific binding of both 125I-gastrin and 125I-CCK-8 was displaced in a concentration-dependent manner by various related peptides with a relative potency order of CCK-8 > or = gastrin < des(SO3)CCK-8. In addition, L364,718 as well as L365,260 displaced the binding of both ligands with similar potencies. Furthermore, not only gastrin but also CCK-8 increased [Ca2+]i in these tumor cells, the action of both being inhibited by L364,718 as well as by L365,260 (10(-7) M). These results suggest that the carcinoid tumor of Mastomys possesses a high affinity gastrin/CCK binding site coupled to the increase of [Ca2+]i.

Animals↗

PubMed1993

Generation and characterization of monoclonal antibodies against rabbit CD4, CD5 and CD11a antigens.

We describe in this report the production and characterization of monoclonal antibodies (mAb) to the rabbit homologues of CD4, CD5 and CD11a antigens, and their use for phenotypic analysis of rabbit lymphoid cell lines. All the mAbs were produced by immunizing mice with rabbit thymocytes. mAb KEN-4 apparently identified rabbit CD4, precipitated two bands of 42 and 50 kDa under reducing and non-reducing conditions and markedly inhibited allo-MLR. The distribution of antigen-positive cells were restricted to the thymus and classical T-dependent areas in peripheral lymphoid tissues. mAb KEN-5 apparently identified rabbit CD5, precipitated a single polypeptide of 67 kDa similar to other anti-CD5 mAb in the human and mouse. The use of this mAb revealed that CD5+ B cells were infrequent in this species. mAb KEN-11 apparently identified rabbit CD11a and precipitated a heterodimer of 150/95 kDa by selectively recognizing the 150 kDa moiety. It blocked cation-dependent aggregation of phorbol ester-induced rabbit Con A blasts and also allo-MLR in a similar manner to other anti-CD11a mAb in various animal species. Phenotypic examination of HTLV-1 transformed rabbit lymphoid cell lines using these mAb clearly indicated that most of them were CD4+, CD5+ and CD11a+, and hence derived from CD4+ T cells. These mAb will be useful tools for the study of the cellular immune system in the rabbit.

Animals↗

PubMed1993

Pharmacokinetic profiles of glycyrrhizin in patients with chronic hepatitis.

The pharmacokinetics of glycyrrhizin (G) in eight patients with chronic hepatitis receiving chronically i.v. administration of 120 mg dose of G was investigated. The plasma concentration of G in the patients after dosing declined in a monophasic manner. However, the pharmacokinetic profiles varied among patients. The mean elimination half-life (t1/2) and the total body clearance (CLtot) were 6.0 h (range 4.3-10.7 h) and 7.9 ml h-1 kg-1 (4.5-12.7 ml h-1 kg-1), respectively. The variation of the CLtot for G was closely related to that of aspartate aminotransferase (r = -0.739, p < 0.05) and alanine aminotransferase (r = -0.783, p < 0.05) activities in the plasma.

Adult↗