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Biomedical subjects

K Yagi

Publications and source records attributed to K Yagi.

At least 181 records · Page 10Linked to original sources
PubMed1998

CD34+ progenitor cell transplantation from two HLA-mismatched healthy fathers to two infants with severe aplastic anemia.

Pluripotent stem cells of hematopoiesis are included among CD34+ cells in the blood and bone marrow. After granulocyte-colony stimulating factor (G-CSF) mobilization, 1-2% of the mononuclear cells in the blood are CD34+ cells, which can be obtained by leukapheresis. We performed CD34+ progenitor cell transplantation in two children with severe aplastic anemia (SAA) who lacked HLA-matched donors. The donors were treated with G-CSF, 600 micrograms/body/day subcutaneously, for 4-5 days. CD34+ cell selection was performed from the apheresis concentrate with mouse anti-CD34 antibody 9C5 and magnet beads coated with sheep anti-mouse IgG1. After the transplantation, the patients received tacrolimus to prevent graft-versus-host disease (GVHD). G-CSF was given to both patients. A mean number of 4.96 x 10(6) CD34+ cells per kilogram of body weight were transplanted. The hematopoietic recovery after the CD34+ cell transplantation was rapid, except for platelets, and acute GVHD was less than or equal to grade I. Case 1, who demonstrated mixed chimerism, anemia and thrombocytopenia after the graft, received a second transplant with intensified preconditioning, and now sustains complete and stable hematopoiesis after a follow-up of 314 days posttransplant. Although Case 2 showed early rejection and received a second transplant, sustained engraftment was never achieved. However, the patient's own hematopoiesis appeared. For SAA patients who do not have HLA-matched donors, this type of approach seems to be a feasible and useful method. However, an intensified preconditioning regimen to overcome the high likelihood of rejection should be employed.

Adult↗
PubMed1998

Time-course of antibody response in mice against oral infection with eggs of Echinococcus multilocularis.

The kinetics of serum antibody response against infection with Echinococcus multilocularis eggs was evaluated in AKR mice. The animals were infected by oral inoculation with 300 parasite eggs, and necropsied at 1, 2, 4, 6, 9, 12 and 16 weeks post-infection (p.i.), respectively. The parasite formed the laminated layer at 4 weeks p.i., the brood capsule with a massive proliferation of germinal cells at 9 weeks p.i. and protoscoleces at 16 weeks p.i. Serum antibody responses of the mice to antigen preparations from metacestodes of different stages and protoscoleces were evaluated by ELISA, immunoblotting and immunohistochemistry. In ELISA, the antibody responses began to increase at 4 weeks and became more apparent at 9 weeks p.i. and thereafter. Immunoblots using sera collected at 16 weeks p.i. showed some common bands among the 3 different antigen preparations. In addition to this, the germinal cells and brood capsules of mature metacestodes were stained strongly in an immunohistochemical study. From above, it is suggested that some antigen molecules are expressed in the parasite through these stages and stimulated host antibody responses.

Animals↗
PubMed1998

Arsenic induces apoptosis in B-cell leukaemic cell lines in vitro: activation of caspases and down-regulation of Bcl-2 protein.

We showed that arsenic inhibited the cell growth of four B-cell leukaemia cell lines of 11 various cell lines in vitro. In two of these four lines, KOCL44 and LyH7, apoptosis was identified by morphological and nucleosomal DNA fragmentation studies. Three of the four B-cell lines that were growth inhibited were acute infantile leukaemia with t(11;19)(q23;p13) translocations involving the MLL gene that encodes the transcriptional factor Drosophila trithorax. The arsenic-induced apoptosis in KOCL44 and LyH7 cells was found to be linked to caspases by Western blot and enzymological analyses. The amount of Bcl-2 was reduced during apoptosis in LyH7 as judged by Western blot analysis. We concluded that combined activation of the caspases and down-regulation of Bcl-2 could determine the fate of B-cell leukaemic cells in response to arsenic.

Animals↗
PubMed1998

Oxytocin release from the neurohypophysis after the taste stimuli previously paired with intravenous cholecystokinin in anaesthetized rats.

Intravenously administered cholecystokinin octapeptide (CCK) induces oxytocin release from the neurohypophysis in anaesthetised rats. Memory of conditioned taste aversion can be acquired under anaesthesia. The present experiments aimed at investigating whether taste stimuli previously paired with i.v. CCK evoke oxytocin release from the neurohypophysis in urethane-anaesthetised male rats. Sucrose solution (0.75-2.0 M) paired with i.v. CCK or the vehicle was applied to the tongue. After 3 h, sucrose solution was applied again. The second sucrose slightly increased plasma oxytocin concentration in rats that had received the first sucrose solution paired with the vehicle. Plasma oxytocin concentration after the second sucrose application, however, was significantly higher in CCK-injected than in vehicle-injected rats. In rats that received CCK 1 h before the first sucrose application, a second sucrose application did not produce the oxytocin response. The magnitude of the oxytocin response to the second sucrose solution was increased in a manner related to CCK doses. In separate experiments, NaCl solution (0.75 M) paired with CCK or the vehicle was applied to the tongue. The second NaCl solution applied 3 h after the first one facilitated oxytocin release both in the rats that had received CCK or the vehicle. The increase in plasma oxytocin, however, was significantly larger in CCK than in vehicle-injected rats. In rats that had received the first sucrose solution paired with CCK, a second sucrose solution evoked a significantly larger increase in plasma oxytocin concentrations than a testing NaCl solution did. In rats that had received NaCl solution paired with CCK, a testing sucrose solution did not significantly change plasma oxytocin concentrations. These data suggest that the taste stimulus previously paired with i.v. CCK induces oxytocin release from the neurohypophysis in urethane-anaesthetised rats.

Anesthetics, Intravenous↗
PubMed1998

Role of adrenoceptors in vasopressin, oxytocin and prolactin responses to conditioned fear stimuli in the rat.

Conditioned fear or novel environmental stimuli suppress vasopressin (VP) and augment oxytocin (OT) and prolactin (PRL) release in rats. We examined the effects of intracerebroventricular (i.c.v.) injections of adrenoceptor antagonists on these neuroendocrine responses to conditioned fear or novel environmental stimuli in male rats. A beta1 antagonist, metoprolol, blocked the VP but not the OT or PRL response to conditioned fear stimuli, but did not abolish neuroendocrine responses to novel environmental stimuli. A beta2 antagonist, ICI118551, impaired the PRL but not the VP or OT response to fear or novel environmental stimuli. In rats injected with a alpha1 adrenoceptor antagonist, benoxathian, conditioned fear stimuli did not significantly induce the VP, OT or PRL responses. The effects of benoxathian were not due to a general reduction of arousal, since benoxathian did not prevent the VP, OT or PRL response to novel environmental stimuli. These data suggest that beta1 adrenoceptors play a selective role in the VP response to conditioned fear stimuli, as do beta2 adrenoceptors in the prolactin response to conditioned fear and novel environmental stimuli. We conclude that alpha1 adrenoceptors play a facilitative role in VP, OT, PRL responses to conditioned fear stimuli.

Adrenergic Antagonists↗
PubMed1998

Follow-up study of children with nephrotic syndrome treated with a long-term moderate dose of cyclosporine.

Because of its potential for chronic nephrotoxicity, the long-term use of cyclosporine A (CsA) as treatment for nephrotic syndrome (NS) is controversial. The clinical outcome of patients with NS treated with CsA is unclear. We retrospectively evaluated 35 children with idiopathic NS, 24 with steroid-dependent NS (SDNS), and 11 with steroid-resistant NS (SRNS), who received CsA therapy for more than 12 months (median, 23 months) at the dosage maintaining 50 to 120 ng/mL in trough level. For SDNS patients, CsA was added to prednisolone after complete remission was achieved. For SRNS patients, CsA was used in combination with alternate-day prednisolone. Initial renal histology showed minimal changes (MC) in 28 patients (including all of the patients with SDNS) and focal segmental glomerulosclerosis (FSGS) in seven patients. The patients were followed up for 2 to 10.5 years (median, 6.5 years) after the termination of the CsA therapy. In SDNS patients, the relapse rate, dosage of prednisolone, standard deviation score for height, and body mass index significantly improved during CsA treatment. The follow-up study showed the proportion of SDNS decreased to 13 of 24 (54%) patients. In SRNS patients, CsA therapy induced remission in 8 of 11 patients (73%) (complete remission in seven and incomplete remission in one). Six of 11 patients (55%) then became steroid sensitive. Post-therapy biopsies, performed in 13 patients (10 with SDNS and three with SRNS), showed mild stripped interstitial fibrosis in two SDNS patients (15%). Long-term CsA therapy in moderate doses was effective to the patients with SDNS and SRNS and low in incidence of nephrotoxicity. The long-term use of CsA appears to result in a decrease in the proportion of SDNS and acquisition of subsequent steroid responsiveness in SRNS.

Adolescent↗
PubMed1998

Effects of short- and long-term exposure to linoleic acid hydroperoxide on cytosolic calcium ion level of human aortic intimal smooth muscle cells in vitro.

When cultured intimal smooth muscle cells from human aorta were exposed for a short period of time (25 sec) to linoleic acid hydroperoxide (100 nmol/ml), influx of calcium ions into the cytosol of these cells was provoked, and a temporal increase in cytosolic calcium ion level was observed. Two calcium channel blockers inhibited this influx. Long-term exposure (4 min) of these cells to the hydroperoxide also provoked the influx of calcium ions, which resulted in a longer time of the calcium ion increase. In the latter case, however, the calcium channel blocker inhibited the initial influx, but then the influx started and continued even in the presence of the blocker. Such difference in exposure time-dependent effects should be taken into account in considering pathological roles of lipid hydroperoxides.

Aorta, Thoracic↗
PubMed1998

Effect on colon cancer cells of human interferon-beta gene entrapped in cationic multilamellar liposomes.

When cultured cells of human colon cancer cell line SW480 were transfected with human interferon-beta (hIFN-beta) gene by means of cationic multilamellar liposomes, the endogenously produced hIFN-beta exhibited a remarkable anti-proliferative effect on the cells, which was more effective than that of exogenously added hIFN-beta. This effect lasted for several days, and was blocked completely by the addition of sufficient amounts of anti-hIFN-beta antibody. From experiments using a transwell plate and an infusion pump, we found that endogenously produced hIFN-beta acted effectively on the cells around the transfectants and that the growth-inhibitory effect was totally retained upon continuous dilution of the medium. These data indicate that hIFN-beta expressed endogenously by transfer of its gene acted on these cancer cells mainly in a paracrine manner. Although the transfection with hIFN-gamma gene also revealed a definite growth-inhibitory effect on the same tumor cells, the extent was less than that of hIFN-beta gene.

Antibodies↗
PubMed1998

Glycated protein-iron chelate increases lipid peroxide level in cultured aortic endothelial and smooth muscle cells.

Formation of an iron chelate of glycated protein was demonstrated by the appearance of an absorption peak at approximately 270 nm after mixing glycated bovine serum albumin with FeCl3. This peak disappeared and a new peak appeared at approximately 420 nm to form an isosbestic point at approximately 340 nm by the addition of deferoxamine mesylate, an iron-chelating agent, to the mixture, thus confirming the formation of the iron chelate of the glycated protein in the mixture. The lipid peroxide level was increased markedly in endothelial cells and slightly in smooth muscle cells from bovine aorta incubated in the medium containing glycated fetal bovine serum-iron chelate. Morphological observation by phase-contrast microscopy and scanning electron microscopy revealed that the glycated fetal bovine serum-iron chelate caused intense damage to the endothelial cells. These results indicate that glycated protein-iron chelate provokes lipid peroxidation, which explains at least in part the mechanism of atherogenesis found in diabetic patients.

Animals↗
PubMed1998

Peroxide production and apoptosis in cultured cells carrying mtDNA mutation causing encephalomyopathy.

When cybrids with a point mutation, which locates in the tRNALeu(UUR) gene of mtDNA and causes a mitochondrial encephalomyopathy (MELAS syndrome), were exposed to a high concentration of oxygen (95%), the peroxide production markedly increased by 6 h of oxygen exposure, whereas the peroxide production was similar among the cybrids under a normal concentration of oxygen. The peroxide production by oxygen exposure was enhanced particularly in cybrids with high proportions of the mutant mtDNA and low respiratory capacities. The appearance of apoptotic cells by oxygen exposure was high in cybrids with the impaired respiratory function due to the mutation. An antioxidant NAC successfully suppressed both the peroxide production and apoptosis. These results imply that the peroxide production plays an important role in inducing apoptosis in cells carrying the mtDNA mutation causing encephalomyopathy.

Acetylcysteine↗
PubMed1998

Long-term course of West syndrome associated with tuberous sclerosis.

We retrospectively analyzed the long-term clinical profiles of 47 patients with West syndrome (WS) associated with tuberous sclerosis (TS) the follow-up study for >10 years showed that WS developed into epilepsies of various types in all patients. Their final diagnoses were symptomatic generalized epilepsy (SGE: 29 patients, 62%), symptomatic partial epilepsy (PE: 14 patients, 30%), and undetermined epilepsy (UE: 4 patients, 8%). Eighty-five percent of all patients continued to show the same types of epilepsy that they had at their first examination, but in 15% the diagnosis had to be revised at the end of the follow-up period. The outcome of seizures was unfavorable for the SGE group. In the PE group, however, seizures were controlled in 9 (64%) of the 14 patients, and disturbances of daily activity were mild. In patients with WS associated with TS, the seizure outcome and social activity varied depending on the type of epilepsy or epileptic syndrome that developed from WS. The complicated clinical developments from WS with TS multiple cortical tubers related to epileptogenesis in addition to impairment of brain development.

Adolescent↗
PubMed1998

Endogenous calcitonin gene-related peptide modulates tachycardiac but not bradycardiac baroreflex in rats.

Effects of intracisternally administered human calcitonin gene-related peptide (8-37) [hCGRP-(8-37)], an antagonist, and hCGRP, an agonist of the CGRP receptor in the rat central nervous system, on baroreflex sensitivity (BRS) were studied in conscious male rats. Each rat sequentially received intracisternally injected 0.9% saline and then hCGRP-(8-37) at doses of 1, 2.5, and 5 nmol in a volume of 10 microliters at an interval of 15 min. Five minutes after each injection, sodium nitroprusside (SNP, 10 micrograms/kg) or phenylephrine hydrochloride (PE, 2 micrograms/kg) was intravenously administered to induce reflex tachycardia or bradycardia, respectively. Intracisternally administered hCGRP-(8-37) increased BRS of the reflex tachycardia induced by SNP in a dose-related manner but did not change the BRS after PE. Intracisternally injected hCGRP significantly decreased the BRS after SNP. The lowering effect of hCGRP on BRS after SNP was inhibited by hCGRP-(8-37) injected before hCGRP. These results suggest that endogenous CGRP in the lower brain stem is selectively involved in the tachycardiac but not the bradycardiac baroreflex and modulates the baroreflex in an inhibitory rather than facilitatory fashion.

Animals↗
PubMed1998

Coproantigen detection in a survey of Echinococcus multilocularis infection among red foxes, Vulpes vulpes schrencki, in Hokkaido, Japan.

Detection of Echinococcus coproantigen using sandwich enzyme-linked immunosorbent assay (sELISA) was performed on fecal samples of red foxes in Hokkaido, Japan. Fecal samples were collected around fox dens in 1990 and 1992. The antibodies used for sELISA recognize heat-resistant antigens, thus all fecal samples were heated to render it safe for handling before examination. Detection of taeniid egg in fox feces collected was considered as an indication of E. multilocularis infection. In fecal samples collected in 1990 and 1992, coproantigen positive results out of taeniid-egg positive cases were 38/40 (95.0%) and 95/97 (97.9%), respectively. In addition, coproantigen was detected regardless of fecal condition when collected from the field, suggesting that the antigens detected by this method are quite stable. These results suggest that detection of coproantigen is useful for field surveys of foxes naturally infected with E. multilocularis.

Animals↗
PubMed1998

Computerized tomography angiography of ruptured cerebral aneurysms: factors affecting time to maximum contrast concentration.

OBJECT: This study was conducted to assess the diagnostic value of three-dimensional computerized tomography (3-D CT) angiography in demonstrating cerebral aneurysms in 42 consecutive patients presenting with acute subarachnoid hemorrhage (SAH). METHODS: To obtain the volume data for selective visualization of the cerebral arteries without enhancement of the venous system, the time delay was established between the injection of contrast medium and the start of scanning by using two different methods. The circulation time was calculated with Schad's formula in the first 13 cases, but the results were not satisfactory. In the 29 subsequent cases the time delay was established using a single-level dynamic CT prescan. The dynamic prescan demonstrated the statistical differences in peak time with regard to patient age, SAH grade, and the postresuscitation state after cardiopulmonary arrest. The 3-D CT angiograms were generated from the volume data by using a voxel transmission method. Computerized tomography angiography obtained after optimally adjusted time delay demonstrated the contour of the cerebral arteries in 97% of cases, and aneurysms were detected in 93%. Enhancement of the cavernous sinus and major cortical veins was avoided. Even in patients who suffered cardiopulmonary arrest, images of the major arteries were clearly demonstrated after resuscitation. CONCLUSIONS: In an emergency situation, CT angiography with a dynamic prescan may be an alternative to magnetic resonance angiography or digital subtraction angiography in the diagnosis of ruptured aneurysms. This modality would also be useful for the precise assessment of small aneurysms, blebs, and aneurysms adjacent to the cavernous sinus.

Adult↗
PubMed1998

[Hepatic osteodystrophy].

Bone thinning causing both fractures and severe pain not associated with fractures has been recognized in patients with chronic liver diseases. The patients most commonly affected are those with primary or secondary biliary cirrhosis, but those with alcoholic liver disease and cirrhosis after active chronic hepatitis may also be involved. Chronic liver disease has also been recognized as an important cause of osteoporosis in both sexes, with the mechanism thought to be a combination of calcium and/or vitamin D. The 9.1% patients with chronic active hepatitis accompanied with osteodystrophy. But 50% cirrhotic patients accompanied with osteodystrophy. Bone densitometry was determined by Digital Image Processing Method (Osteodystrophy < mean-2SD: age- and sex-matched normal value). Serum levels of osteocalcin (BGP) and parathyroid hormone (PTH) in patients of hepatic cirrhosis without osteodystrophy were lower than those with osteodystrophy. These results were suggested that hepatic osteodystrophy was rapidly turnover osteodystrophy. To function physiologically, vitamin D must be hydroxylation in liver to 25-(OH)-D and subsequently by the kidney to 1 alfa, 25-(OH)2-D. Osteodystrophy associated with hepatic cirrhosis is due to a defect in the 1 alfa-hydroxylation by the kidney rather than a hepatic hydroxylation defect. 1 alfa OH-D3 is very useful for treatment for hepatic osteodystrophy.

Bone Diseases↗
PubMed1998

Antisense oligonucleotides against collagen-binding stress protein HSP47 suppress collagen accumulation in experimental glomerulonephritis.

Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been shown to play a major role during the biosynthesis and secretion of procollagen molecules. The expression of HSP47 has been reported to increase in parallel with the expression of collagens during the progression of various fibrosis models. However, it remains unclear whether an inhibition of HSP47 overexpression would suppress collagen accumulation and thus reduce the progression of fibrotic diseases. In this study, we attempted to attenuate glomerular collagen accumulation by inhibiting the overexpression of HSP47 with antisense oligodeoxynucleotides in an experimental glomerulonephritis model induced by anti-Thy-1 antibodies. The administration of antisense oligodeoxynucleotides against HSP47 at the induction of the glomerular disease markedly suppressed the increased production of collagens and attenuated the histologic manifestations of the disease. These results provide direct evidence of a pivotal role for HSP47 in the pathogenesis of glomerulonephritis.

Animals↗