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Biomedical subjects

K Koide

Publications and source records attributed to K Koide.

At least 55 records · Page 3Linked to original sources

In vivo effect of prednisolone on release of leukotriene C4 in eosinophils obtained from asthmatic patients.

We investigated the release of leukotriene C4 from eosinophils of asthmatic patients who were treated with or without intravenous prednisolone. The mean level of LTC4 in the supernatant of A23187-stimulated eosinophils obtained from asthmatic patients during an attack was significantly lower with intravenous prednisolone than without prednisolone treatment. Findings suggest that intravenous prednisolone inhibits the release of LTC4 from the eosinophils of asthmatic patients by acting on these cells in vivo.

Adult↗

Molecular design and biological activity of potent and selective protein kinase inhibitors related to balanol.

BACKGROUND: The protein kinase C (PKC) family of serine/threonine-specific protein kinases is involved in many cellular processes, and the unregulated activation of PKC has been implicated in carcinogenesis. PKC inhibitors thus have significant potential as chemotherapeutic agents. Recently, the fungal metabolite balanol was shown to be an exceptionally potent inhibitor of PKC. We previously developed a practical and efficient total synthesis of balanol. We set out to use this synthetic molecule, and several synthetic analogs, to probe the mechanism of PKC inhibition and to determine the effect of balanol on the activity of other protein kinases. RESULTS: As well as inhibiting PKC, balanol is a potent inhibitor of cyclic AMP-dependent protein kinase (PKA), another protein serine/threonine kinase. Balanol does not, however, inhibit the Src or epidermal growth factor receptor protein tyrosine kinases. The inhibition of both PKC and PKA by balanol can be overcome by high concentrations of ATP, and molecular modeling studies suggest that balanol may function as an ATP structural analog. Although balanol discriminates rather poorly between PKC and PKA, only minor modifications to its molecular structure are required to furnish compounds that are highly specific inhibitors of PKA. CONCLUSIONS: A number of balanol analogs have been designed and synthesized that, unlike balanol itself, exhibit dramatic selectivity between PKA and PKC. Thus, despite the substantial homology between the catalytic domains of PKA and PKC, there is enough difference to allow for the development of potent and selective inhibitors acting in this region. These inhibitors should be useful tools for analyzing signal transduction pathways and may also aid in the development of drugs with significant therapeutic potential.

Adenosine Triphosphate↗

[A hemodialysis patient with HTLV-1-associated myelopathy (HAM)].

We report here a case of maintenance hemodialysis with HTLV-1 associated myelopathy (HAM). A 53-year-old female hemodialysis patient was admitted to Teikyo University Ichihara hospital because of paralytic ileus. She had a history of blood transfusion and had been under dialysis treatment for 8 years. She had experienced gait disturbance and sensory disturbance in her lower extremities for 8 years. Neurological examination revealed myelopathy and neuropathy. Laboratory data revealed that serum anti-HTLV-1-antibody was over 1260 x (PA) and liquor HTLV-1-antibody was over 160 x (PA). Her liquor revealed a cell count of 4/3 cmm, protein 22 mg/dl, glucose 45 mg/dl, chloride 125 mEq/l and no atypical cells. To the best of our knowledge this is a rare case in Japan. Our findings suggest that HAM should be taken into consideration when we diagnose a maintenance hemodialysis patient showing neuropathy and myelopathy.

Female↗

[An adult case of hemolytic uremic syndrome (HUS) after pathogenic Escherichia coli (E. coli) infection].

In recent years, it has been revealed that verocytotoxin-producing E. coli (VTEC) infection is one of the leading causes of HUS and the molecular aspects of its pathophysiology have also been studied extensively. We report a case of a 56-year-old man who developed HUS after E. coli (O 26 strain) infection with diarrhea. The characteristic laboratory findings in this case included hypergammaglobulinemia, hypocomplementemia and a high level of immune complex in addition to the common findings of HUS. The light microscopic findings of the first renal biopsy performed before treatment revealed extensive interstitial changes with remarkable mononuclear cell infiltrations as well as mild mesangial proliferation with crescent formation. Subendothelial electron-dense deposits within the glomerular capillary walls and mesangial area were also detected by electron microscopic examination. The diagnostic possibilities of infectious endocarditis and collagen diseases, such as Sjögren syndrome, were reasonably ruled out by the appropriate examinations. After 2-month prednisolone therapy, proteinuria and deteriorated renal functions as well as the abnormal immunological parameters described above were remarkably improved. The second renal biopsy after treatments showed clearly diminished subendothelial deposits and interstitial mononuclear cell infiltrations. This case report might provide information on the unique features of renal interstitial damage and immunological abnormalities in VTEC-induced adult HUS.

Bacterial Toxins↗

[Secondary hyperparathyroidism and tertiary hyperparathyroidism chronic renal failure, uremia].

The bone histology of renal osteodystrophy is classified into osteitis fibrosa, osteomalacia, those of mixed, osteoporosis and low turnover bone. Osteitis fibrosa is the most frequent skeletal abnormality and is caused by various degrees of hyperparathyroidism. The main factors inducing hyperparathyroidism which is a well known complication in patients with renal failure include (a) phosphorus retention: 1) hypocalcemia and 2) decreased levels of 1 alpha, 25(OH)2 Vitamin D3, (b) reduced number of 1 alpha, 25(OH)2 Vitamin D3 receptors in parathyroid tissue, (c) skeletal resistance to set-point for calcium-regulated parathyroid hormone secretion. Serum or plasma levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone, calcitonin and tartrate resistant acid phosphatase are measured to evaluate hyperparathyroidism and metabolic bone disease. Dietary phosphorus restriction in chronic renal insufficiency prevents secondary hyperparathyroidism and renal osteodystrophy. Other treatment of phosphorus binders, Vitamin D metabolites or analogues, carcitonin and bisphosphonate are useful for the management of renal bone disease.

Calcitriol↗

A high-level and regulatable production system for recombinant glycoproteins using a human interferon-alpha promoter-based expression vector.

A novel expression vector for human cells, pIFP, which expresses a cloned gene under the control of the human interferon-alpha-encoding gene (IFN-alpha) promoter (pIFN) was constructed. As a model of glycoprotein production, a human erythropoietin-encoding cDNA (EPO) inserted downstream from pIFN in pIFP was introduced into human B-cell leukemia-derived BALL-1 cells, and EPO-producing cells were established. Upon stimulation with Sendai virus, the cells produced human EPO at high levels. The highest production level and the highest inducibility were 872 IU/ml and 67-fold, respectively. Simultaneously, the transformed cells also produced IFN-alpha and tumor necrosis factor-alpha (TNF-alpha), as the parental BALL-1 cells did. Comparing the amounts of the substances produced, activity of the exogenous pIFN introduced seemed much higher than that of the endogenous one. Further, the transformed cells could be obtained in a large quantity by being applied to the 'in vivo cell proliferation method (hamster method)'. Human EPO produced by the transformed cells had a molecular mass range of 35 to 42 kDa, similar to that of EPO produced by CHO cells. The processing of EPO seemed to occur properly. The combination of the human pIFN, BALL-1 cells and the hamster method provides us with a useful production system for bioactive glycoproteins of human origin.

Animals↗

Peripheral anterior inferior cerebellar artery aneurysms.

Two cases of peripheral anterior inferior cerebellar artery (AICA) aneurysms are reported. The first case was a 60-year-old man who showed frequent attacks of subarachnoid hemorrhage (SAH) and hearing disturbance. His aneurysm was obliterated by trapping the AICA and his neurologic status was unchanged compared with preoperatively. The second case had SAH without cranial nerve involvement; this aneurysm was obliterated by neck clipping. He was discharged without neurologic deficit. Peripheral AICA aneurysm has already been reported in 48 cases including arteriovenous malformation-associated cases. This aneurysm may show cranial nerve involvement (seventh and eighth) without SAH as in the case of internal carotid-posterior communicating artery aneurysms. We review the clinical signs of these cases and discuss them from the point of view of anatomic variations of the AICA and internal auditory artery.

Aged↗

Striatal grafts in infarct striatopallidum increase GABA release, reorganize GABAA receptor and improve water-maze learning in the rat.

We grafted fetal striatal cells in ischemic rat models, and investigated graft survival/growth, GABA release, GABAA receptor reorganization and functional recovery. One hour intraluminal occlusion of the middle cerebral artery (MCA) induced ischemic infarct in the lateral part of the striatum and adjacent cortex. In ischemic rats, the acquisition of Morris' water-maze learning was significantly slower than that of control rats. In these animals GABA level in the globus pallidus, detected by microdialysis, was about the half of that of controls. However, after the grafts of fetal striatal cells in the striatopallidum, the acquisition was improved, thus no difference was observed in the time course of learning curves in control and grafted animals. GABA level recovered to almost normal level by the graft. It further increased by the treatment of a GABA uptake blocker (nipecotic acids) in the perfusion. In the grafts, GABAA receptor organization detected by autoradiography using [3H] labeled SR95531 was restored for more than 1 year after the graft. Data suggest that fetal striatal cell grafts in infarct striatum may partially reconstruct striatopallidal GABA projection and reorganize GABAA receptor. This might be a basis of improvement of function.

Animals↗

[Glucocorticoid therapy in renal diseases--its indication and therapeutic schedule].

Glucocorticoid therapy is used to treat renal diseases because of the two pharmacological actions, i.e anti-inflammatory and Immunosuppressive ones. Indications for steroid therapy in renal diseases are mainly primary and secondary nephritis and the nephrotic syndrome. These include minimal change nephrotic syndrome, membranous nephropathy, membranoproliferative glomerulonephritis, focal glomerular sclerosis, rapidly progressive glomerulonephritis, IgA nephropathy (in part), lupus nephritis, acute interstitial nephritis and so on. There are two routes of steroid administration, orally or intravenously, to treat nephritis and the nephrotic syndrome. The standard therapeutic regimen is the oral administration of prednisolone (PSL), which usually consists of initial high dose therapy (40-60 mg/day), subsequent withdrawal of steroids and maintenance therapy. As for intravenous administration, high dose injection of methylprednisolone (usually 1000 mg on three successive days) is utilized and followed by high dose oral PSL.

Administration, Oral↗

Striatal grafts in the ischemic striatum improve pallidal GABA release and passive avoidance.

Fetal striatal cells were grafted into the ischemic striatum of rats and pallidal GABA release, and behavioral improvement were investigated. Intraluminal occlusion of the middle cerebral artery (MCA) for 1 h induced ischemic infarcts in the lateral striatum and the adjacent cortex. In ischemic rats, the performance of a passive avoidance task was disturbed, and the pallidal GABA level detected by microdialysis decreased to about a half of control. After the graft, the deficit in the passive avoidance was partially alleviated and the GABA level recovered moderately and increased further by the infusion of an uptake blocker. The data indicate that fetal striatal cell grafts in the ischemic striatum partially restored both chemical and behavioral deficits.

Animals↗

Bactericidal effects of povidone-iodine solution to oral pathogenic bacteria in vitro.

Seven species of periodontal pathogenic bacteria (Bacteroides, gingivalis, Bacteroides intermedius, Bacteroides melaninogenicus, Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Capnocytophaga spp., Eikenella corrodens) and two control species (Streptococcus intermedius, Pseudomonas aeruginosa) were selected in order to study the bactericidal effects of 10% povidone-iodine (PVP-I) aqueous solution in vitro. The PVP-I solution was diluted to 10, 20, 50, 100, 200, 400, 800, 1600, 3200, 6400 and 12800 x and contact times were 15, 30 and 60 seconds. The strongest bactericidal effects on the seven periodontal pathogenic bacteria and two control bacteria were seen at a dilution of 400 x and a contact time of 15 seconds. Based on these findings, we advocate a 0.25% solution of 10% aqueous PVP-I for oral mucosa and periodontal pocket irrigation.

Aggregatibacter actinomycetemcomitans↗