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Biomedical subjects

K Shibata

Publications and source records attributed to K Shibata.

At least 199 records · Page 11Linked to original sources
PubMed1998

Ovariectomy-induced hyperalgesia and antinociceptive effect of elcatonin, a synthetic eel calcitonin.

Using ovariectomized (OVX) rats in the tail-withdrawal nociceptive test, we examined OVX-induced hyperalgesia and the antinociceptive effect of subcutaneously administered elcatonin, a synthetic derivative of eel calcitonin ([Asu1.7] eel calcitonin). Because tail-withdrawal latency was significantly and continuously reduced and bone mineral density decreased in OVX rats compared with those of sham-operated rats, it was demonstrated that ovariectomy induced prolonged hyperalgesia and osteoporosis. After repeated administrations for 3 or 4 weeks, subcutaneously injected elcatonin increased the latency of the OVX rats in a dose-dependent manner, compared to the vehicle-treated OVX rats. At a dose of 20 U/kg/day, there were significant differences (p < 0.01) in the latency between the elcatonin- and vehicle-treated OVX rats. This effect of elcatonin was completely inhibited by p-chlorophenylalanine treatment, suggesting that the central serotonergic system may be involved in the elcatonin antinociception of OVX-induced hyperalgesia.

Analgesics↗
PubMed1998

Hybrid peptides constructed from RES-701-1, an endothelin B receptor antagonist, and endothelin; binding selectivity for endothelin receptors and their pharmacological activity.

Hybrid peptides were constructed from endothelin B receptor (ET(B)) selective antagonist RES-701-1 (1) and endothelin (ET-1). They have N-terminal 10 amino acids derived from 1 and C-terminal 10 amino acids derived from ET-1. RES-701-1(1-10)-[Ala15]ET-1(12-21) and its analogues substituted or truncated at the residues derived from RES-701-1 had proved to possess high receptor binding activity selective for ETB as well as 1. Substitutions at the residues derived from ET-1 had produced some analogues that possessed high affinity not only for ETB but for ETA. Although all analogues had antagonistic effects on ETA, some analogues had proved to function as agonist on ETB confirmed by the changes in intracellular calcium concentrations of ET receptor-transfected COS-7 cells. We have found four types of ET receptor-binding peptides: (1) ETB-selective agonist with weak ETA antagonism (3, KT7421); (2) ETB-selective antagonist with weak ETA antagonism (29, KT7539); (3) ETB agonist with potent ETA antagonism (27, KT7538); and (4) non-selective ETA/ETB antagonist (26, KT7540).

Amino Acid Sequence↗
PubMed1998

Identification of structural domains in inter-alpha-trypsin involved in calcium oxalate crystallization.

The urinary glycoprotein that inhibits calcium oxalate (CaOx) crystallization in vitro shows a structural similarity to urinary trypsin inhibitor (UTI; recently termed bikunin), the light chain of inter-alpha-trypsin inhibitor (I alpha I). The functional domains of I alpha I involved in its inhibitory activity of CaOx crystallization have been investigated using isolated intact domains of I alpha I produced from controlled proteolytic digests of the protein. The fragments investigated include the heavy chains of I alpha I, UTI, chondroitinase AC-treated UTI, and the carboxyl-terminal domain of UTI (termed HI-8). The effects of I alpha I and its fragments on the inhibitory activity of CaOx crystallization were evaluated in vitro using CaOx crystal aggregation and growth assays, and seeded crystal generation assay as well as using crystal matrix protein generation assay. UTI, but not the heavy chains of I alpha I, had a discernible effect on CaOx crystallization inhibitory activity. Less requirement of the carbohydrate moiety of UTI is implicated by the observation that chondroitinase AC-treated UTI fragment was also found to inhibit CaOx crystallization with almost the same activity as UTI. HI-8 also efficiently inhibited CaOx crystallization, while I alpha I showed a weak inhibitory activity. The results are almost consistent with a seed crystal generation assay and a crystal adsorption inhibition assay, in which I alpha I or its derivatives inhibits prothrombin fragment 1 (F1) adsorption to CaOx crystals. In conclusion, these results suggest that the part of the I alpha I protein responsible for inhibition of CaOx crystallization is the carboxyl-terminal domain of UTI.

Alpha-Globulins↗
PubMed1998

Hemiballism-hemichorea from marked hypotension during spinal anesthesia.

Hemiballism and hemichorea following anesthesia-induced hypotension has rarely been described, but a recent case suggests an association. After experiencing marked hypotension during spinal anesthesia, a 70-year-old woman developed hemiballism and hemichorea. Involuntary ballistic movements with writhing, consisting of repetitive rotation and flexion-extension without apparent muscle weakness, affected her left limbs proximally. Low-amplitude, involuntary, choreiform movements involved the distal portions of these limbs. Magnetic resonance imaging demonstrated an area of high signal intensity in the contralateral subthalamic nucleus, suggestive of a focal ischemic lesion. Although such occurrences are rare, anesthesiologists should be aware of the risk of subthalamic nucleus ischemia following marked hypotension.

Aged↗
PubMed1998

Detection of Mycoplasma salivarium and Mycoplasma fermentans in synovial fluids of temporomandibular joints of patients with disorders in the joints.

Thirty-six synovial fluid samples of temporomandibular joints were obtained from 33 patients with pain and anterior disk displacement (closed lock) in the joints. DNAs were prepared from the samples and amplified by a PCR-based assay specific for Mycoplasma salivarium or Mycoplasma fermentans. Of the 36 samples, five (14%), three (8%), and 19 (53%) were positive for M. salivarium, M. fermentans and both, respectively.

Adolescent↗
PubMed1998

Hypercapnic acidosis may attenuate acute lung injury by inhibition of endogenous xanthine oxidase.

Relative hypoventilation, involving passively-or "permissively"-generated hypercapnic acidosis (HCA), may improve outcome by reducing ventilator-induced lung injury. However, the effects of HCA per se on pulmonary microvascular permeability (Kf,c) in noninjured or injured lungs are unknown. We investigated the effects of HCA in the isolated buffer-perfused rabbit lung, under conditions of: (1) no injury; (2) injury induced by warm ischemia-reperfusion; and (3) injury induced by addition of purine and xanthine oxidase. HCA (fraction of inspired carbon dioxide [FICO2] 12%, 25% versus 5%) had no adverse microvascular effects in uninjured lungs, and prevented (FICO2 25% versus 5%) the increase in Kf,c following warm ischemia-reperfusion. HCA (FICO2 25% versus 5%) reduced the elevation in Kf,c, capillary (Pcap), and pulmonary artery (Ppa) pressures in lung injury induced by exogenous purine/xanthine oxidase; inhibition of endogenous NO synthase in the presence of 25% FICO2 had no effect on Kf,c, but attenuated the reduction of Pcap and Ppa. HCA inhibited the in vitro generation of uric acid from addition of xanthine oxidase to purine. We conclude that in the current models, HCA is not harmful in uninjured lungs, and attenuates injury in free-radical-mediated lung injury, possibly via inhibition of endogenous xanthine oxidase.

Acidosis↗
PubMed1998

Studies on agents with vasodilator and beta-blocking activities. V. Synthesis and pharmacological activity of the optical isomers of TZC-5665.

Synthesis of the four optical isomers of TZC-5665 (1), a candidate for the treatment of congestive heart failure, was achieved by the reaction of chiral diaminopyridazinone (2) with chiral glycidyl ether. (3). The hypotensive and beta-blocking activities of 1 and its optical isomers were examined when given intravenously into anesthetized rats. Furthermore these compounds were evaluated for inhibitory activity on cAMP phosphodiesterase III. Among the four optical isomers, Ra,Sb-one (1c) possessed the essential activities of TZC-5665 (1).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

[Expression of angiotensin type-2 receptors in rat brain during the cell injury].

The present study examined changes in angiotensin type-2(AT2) receptor mRNA level after global brain ischemia or during glutamate neurotoxicity in cultured cortical cells in rats. The AT2 mRNA level increased by three-fold in both the cortex and hippocampus, which are known to be sensitive to ischemic injury, 3 hr after ischemia. The day 10-14 cortical neurons were exposed to glutamate at a toxic concentration of 100 microM for 15 min. AT2 receptor mRNA was then increased 2-fold after exposure to glutamate, while the maximum increase was observed in a dose-dependent manner 3 hr after glutamate stimulation. AT2 receptor binding also increased 3-12 hr after glutamate exposure. The increase in the mRNA level was antagonized by N-nitro L-arginine methyl-ester, a nitric oxide synthase inhibitor. The hemoglobin, a nitric oxide trap, also inhibited the increase in the mRNA level. These results suggest that the increase in the mRNA level is associated with the nitric oxide synthesis by glutamate exposure. The viability of cortical cells after glutamate stimulation was partially restored by the antisense oligonucleotide for the AT2 receptor. The present results thus suggest the AT2 receptor may in some way be related to one of the processes in cell injury.

Animals↗
PubMed1998

Vascular alpha1-adrenoceptor subtype selectivity and alpha1-blocker-induced orthostatic hypotension.

Newly developed alpha1-adrenoceptor antagonists including naftopidil are free from the "prazosin-like" side effect of orthostatic hypotension and associated symptoms. We investigated the mechanism for the differential effects of naftopidil and prazosin on the development of postural hypotension, with special attention on their selectivity for the alpha1-adrenoceptor subtype. We observed that head-up tilt caused a similar extent of drop in mean arterial pressure in control, naftopidil (1 mg/kg)- or prazosin (10 microg/kg)-treated rats; however, the tilt-induced postural hypotension was recovered within 2 min in the naftopidil-treated group, but not in the prazosin-treated group. Comparing an inhibitory effect on noradrenaline-induced contraction in the rat aorta and portal vein, we found that naftopidil was sixfold less potent in the portal vein, while prazosin showed similar potency in both tissues. Reverse transcription-polymerase chain reaction analysis showed that the expression of alpha1d-adrenoceptor mRNA predominated in the aorta, while that of alpha1b-adrenoceptor mRNA predominated in the portal vein. Using cloned rat alpha1-adrenoceptor subtypes, we found that naftopidil was selective for the alpha1d-subtype with approximately ninefold higher affinity than at the other subtypes. These results show that the pharmacological character of naftopidil, combined with the differential expression of the alpha1-adrenoceptor subtype in the artery and the vein, may partly explain the differential effect of naftopidil and prazosin on head-up tilt-induced hemodynamic responses.

Adrenergic alpha-Antagonists↗
PubMed1998

Increased conversion ratio of tryptophan to niacin in severe food restriction.

The effect of food restriction on the conversion ratio of tryptophan to niacin was investigated, because it is known that the conversion ratio is influenced by nutritional factors. A 20% casein diet was fed to rats ad libitum (control), 1/2 the food of the control. 1/4 the food of the control, or starved for 9 days, and urine samples were collected to measure the urinary excretion of such tryptophan metabolites as kynurenic acid, xanthurenic acid, and nicotinamide. The conversion ratio in the 1/2, 1/4, or starving group increased at day 1 of the experiment, but returned to the original value from day 2. Only in the starving group did the conversion ratio extremely increase from day 6 to day 9, being about 5-times higher than that of the original value on day 9. The possible mechanism by which the conversion ratio increased during food restriction is discussed.

Animals↗
PubMed1998

Chylothorax associated with inflammatory carcinoma.

We report a rare case of a woman with inflammatory carcinoma, an unusual type of cutaneous metastasis, arising from signet-ring cell carcinoma of the stomach, who developed chylothorax as the skin lesion progressed over the chest. No thoracoabdominal lymphadenopathy which can cause obstruction of the thoracic duct was shown by computed tomography. Although a very rare condition, inflammatory carcinoma could be a cause of non-traumatic chylothorax.

Adenocarcinoma↗
PubMed1998

Detection of ras gene mutations in peripheral blood of carcinoma patients using CD45 immunomagnetic separation and nested mutant allele specific amplification.

We developed a sensitive technique of detecting circulating tumor cells in carcinoma patients, using CD45 immunomagnetic separation to isolate epithelial cells in blood samples and specific polymerase chain reaction analysis to identify point mutations of the K-ras gene. The method is based on the fact that the peripheral blood mononuclear cells (PBMC) that express CD45 antigen are trapped with anti-CD45 conjugated supramagnetic microbeads while the carcinoma cells that do not express CD45 antigen are not trapped and pass through the magnetic fields. This method concentrated the number of carcinoma cells 3.3 times. After this separation, the modified method of mutant allele specific amplification was applied and this method was able to ten control carcinoma cells in a background of 107 PBMC. A preliminary clinical study demonstrated that six cases of end-stage carcinoma with K-ras mutations in the primary tumor showed the same mutations in the peripheral blood samples, while two cases without K-ras mutation in the primary tumor and 10 healthy volunteers showed no mutation in the peripheral blood samples. The results suggest that this method may be very useful to detect circulating carcinoma cells in the patient whose primary tumor shows K-ras mutations.

Aged↗
PubMed1998

Importance of basophilia in haematopoietic disorders.

To the significance of basophilia in haematopoietic disorders, six draw attention to cases have been analyzed. Associated diseases included acute myelogenous leukaemia (AML-M2, M3, M4, and M6), refractory anaemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T). Two AML cases (M2, M6) were preceeded by myelodysplastic syndromes (MDS). All patients showed greater than 3% basophilia in peripheral blood and bone marrow. Basophils were identified successfully by metachromatic staining with toluidine blue in all cases. Three patients (M3, M4, RAEB) presented with lymphadenopathy, suggesting an association with extramedullary involvement. Neutrophil alkaline phosphatase (NAP) activity was significantly reduced in four patients with AML (M2, M3, M4) and RAEB-T. The clinical course was generally unfavourable characterized by short remission duration or disease progression except for the patient with RAEB. Haemorrhage was the main cause of death rather than infection. Cytogenetic analysis revealed unique abnormalities involving chromosomes 3q21, 5q31, and 17q11 where the genes for some haematopoietic growth factors or their receptors are located, in addition to t(6;9) and t(15;17).

Adolescent↗
PubMed1998

Saccharides as osmotic agents in peritoneal dialysate: determination of molecular weight essential for more efficient fluid removal.

Glucose has widely been used as an osmotic agent in continuous ambulatory peritoneal dialysis (CAPD) but owing to its low molecular weight (MW), ultrafiltration (UF) in a 6-hour dialysate exchange does not appear sufficient. Thus, in the present study, a search was made to find saccharides that would ensure optimal UF, exceeding that obtained with glucose in a 6-hour dwell period. Rats were intraperitoneally infused with peritoneal dialysate (20 mL/body) containing the same molar concentrations (75.5 mM, 126 mM, or 204 mM) of various osmotic agents including glucose (monosaccharide, MW = 180.16) at concentrations of 1.36%, 2.27%, and 3.86%; maltose (disaccharide, MW = 342.30) at concentrations of 2.58% and 4.32%; maltotriose (trisaccharide, MW = 504.44), at concentrations of 3.81% and 6.36%; and maltopentaose (pentasaccharide, MW = 828.72) at concentrations of 6.26% and 10.4%. Intraperitoneal-fluid volume was measured at 1, 2, 3, 4, and 6 hours. With glucose as the osmotic agent, maximal UF was noted at 2 to 4 hours. UF was more efficient at 6 hours with maltotriose or maltopentaose as the osmotic agent. Even with a trisaccharide or pentasaccharide (molecular weights of 500 to 830), UF at 6 hours was found more efficient, as evidenced by the delay in peritoneal absorption. Fluid removal in 6 hours should be greater when using a dialysate containing oligosaccharides such as maltotriose or maltopentaose in place of glucose.

Animals↗
PubMed1998

In vitro and in vivo generation and kinetics of glycosylation products in peritoneal dialysis effluents.

There are indications that advanced glycosylation end-products (AGEs) may affect in some manner the functions of the peritoneum. Only a few reports discuss the actual generation of glycosylated proteins and the intraperitoneal kinetics involved during continuous ambulatory peritoneal dialysis (CAPD). To demonstrate the formation of AGEs and their time-courses in peritoneal dialysis (PD) effluents, measurements were made of furosine, carboxymethyl lysine (CML), and pentosidine as glycosylation markers in vitro and in vivo using PD effluents obtained every 2 hours for up to 8 hours from 3 nondiabetic CAPD patients. Furosine and CML were found to be generated relatively early (within 6 hours), and their de novo formation was markedly enhanced subsequent to glucose addition. Furosine and CML production increased in proportion to glucose concentration. Pentosidine production did not change with time for up to 24 hours, and was not induced by glucose during this period. Carboxymethyl lysine production appeared to be suppressed in vitro with the addition of serum protein. Furosine in the intraperitoneal dialysate was initially the same as that in the plasma, but increased to twice as much in just 2 hours in vivo. Production of CML increased, but apparently was suppressed with leakage of plasma protein into the dialysate; this possibly may have been due to dilutional or antiglycation effects in the plasma. No stimulation of pentosidine production could be detected in the intraperitoneal dialysate even at 8 hours. The initiation of glycosylation of peritoneal proteins, with generation of furosine and CML but not pentosidine, is clearly shown by the present results to occur relatively early in the intraperitoneal dialysate, i.e., within a matter of hours.

Adult↗