Search PubMed⌕ Search

Biomedical subjects

K Hatakeyama

Publications and source records attributed to K Hatakeyama.

At least 253 records · Page 14Linked to original sources

[Evaluation of a latex agglutination method for detecting and characterizing verotoxin (VT) produced by Escherichia coli].

The detection of VT produced by Escherichia coli is very important for the identification of verotoxin-producing Escherichia coli (VTEC). The latex agglutination reagents (Denka Seiken Co. Ltd, Tokyo) which was developed to detect VT was compared with the vero cell bioassay or polymerase chain reaction method. A total 147 VT-positive strains (109 serotype O157:H 7/- and 38 non-O157 serotype) and 31 VT-negative strains which were isolated from human were investigated. In addition, a total of 79 VT-positive strains (14 serotype O157:H7/- and 65 non-O157 serotype) and 79 VT-negative strains which were isolated from animals were also examined. The latex agglutination assay for the human isolates showed the 100% sensitivity, specificity and agreement. The assay for the animal isolates showed 94.9% sensitivity, 100% specificity and 97.5% agreement. Although 4 of 8 strains isolated from swine which produce VT2 variant toxin (VT2e) failed in detecting verotoxin by latex agglutination assay, VT2e was not related to human infections. We conclude that this latex agglutination reagent is highly sensitive and specific for detecting and characterizing VT of E. coli. The method is reliable, easy to perform at any laboratories.

Animals↗

[Efficacy and side effects of lidocaine by intravenous drip infusion in children with intractable seizures].

Intravenous drip infusions of lidocaine (IDIL; 1-5 mg/kg/h) were performed in ten patients with intractable seizures. The medication was very effective in five patients, whose seizures disappeared immediately after the treatment of IDIL. In four patients, the medication proved to be effective judging from decreased incidence of seizures. In one patient with intractable seizures, the therapy was not effective. In nine patients with the effective medication, five had generalized seizures and four had partial seizures. Side effects were observed in four patients. Two patients had muscle hypotonia, one had visual and auditory hallucination and another had bradycardia. These symptoms completely disappeared after the ceasing of IDIL. Serum concentrations of lidocaine at the appearance of the side effects ranged from 1.8 to 4.7 micrograms/ml, although the toxicity level is more than 5.0 micrograms/ml for arrhythmic adult patients. These findings suggest that the serum toxic level of lidocaine in children is different from that in adults, and that careful observation and appropriate management for the children with lidocaine therapy should be necessary, even though the serum level of lidocaine ranges within the therapeutic level.

Adolescent↗

[Cerebral cortical dysplasia associated with epilepsy: MRI and clinical aspects].

Clinical and electroencephalographic (EEG) studies were performed in nine patients with cerebral cortical dysplasia (CD). Interictal single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propylene amine oxime were studied in four patients. A patient with hemimegalencephaly and agyria had poor outcome in both developmental and epileptic aspects. The prognoses of clinical seizures were generally related to the severity, location and size of CD. The size of the lesion was not always correlated with the clinical seizure outcome. Four patients had focal pachygyria. Clinical pictures were diverse in these patients. One patient underwent callosotomy for the control of intractable seizures. The others had no clinical seizures despite of the appearance of paradoxical discharges in the area of pachygyria. The distribution of CD detected by MRI did not always correlate with that of paradoxical discharges in EEG and/or hypoperfusional areas seen in SPECT. These findings suggest that a detailed neuroimaging study is useful to elucidate the epileptogenesis in patients with CD, and that all the cortical abnormalities in patients with intractable epilepsy are not detected by MRI.

Adolescent↗

[Proctocolectomy with ileal W pouch anal anastomosis for ulcerative colitis].

Restorative proctocolectomy with ileal pouch anal anastomosis, which is a relatively new procedure, has become a standard procedure for ulcerative colitis (UC) requiring surgical management. The main impact of this procedure is to cure patients of disease and to avoid permanent ileostomy, preserving better defecatory function and acceptable QOL. Some key aspects of our surgical procedure are as follows: 1) two or three separate staged operation, 2) W-shaped reservoir, 3) distal rectal mucosectomy and handsewn ileo-anal anastomosis, 4) short muscular cuff, and 5) temporary diverting ileostomy. Staged operation and diverting ileostomy are helpful to decrease risk of pelvic infection. Total removal of the rectal mucosa is necessary to cure the disease, and shorter muscular cuff decreases operating time and bleeding and thus the risk of pelvic sepsis. The W-shaped reservoir described by Nicholls brings both spontaneous defecation and improved function. We have adopted ileal W-pouch among several types of reservoir to 58 patients with UC since 1984, and found that a large and wide reservoir might allow better defecatory function. There were no cases of serious complications and no needs to remove the reservoir. Mean daily stool frequency was gradually decreased with time, and 4.9 stools per 24 hours at present day, and clinical score of neorectal function also gradually improved according to reduction of stool frequency. Seventy three percent of patients felt their defecatory function satisfactory and 89% of the patients recovered acceptable QOL no less than that obtained during the medically treated period.

Adolescent↗

Groove pancreatitis with recurrent duodenal obstruction. Report of a case successfully treated with pylorus-preserving pancreaticoduodenectomy.

Groove pancreatitis is a rare subtype of chronic pancreatitis that is difficult to distinguish from pancreatic carcinoma. Most reported patients have undergone a Whipple procedure because pancreatic cancer was not ruled out. We report a case of groove pancreatitis in a patient who presented with recurrent duodenal obstruction without biliary stricture. The diagnosis of groove pancreatitis was based on characteristic episodes of repeated duodenal obstruction and the absence of radiographic evidence of cancer. Subsequently, our patient underwent a successful pylorus-preserving pancreaticoduodenectomy (PPPD). PPPD is a favorable alternative to the Whipple operation for duodenal obstruction resulting from this disease.

Adult↗

[Acute necrotizing encephalopathy with horizontal gaze palsy].

Acute necrotizing encephalopathy (ANE) of childhood is a newly proposed disease entity characterized by symmetrically distributed necrotic brain lesions in the thalamus, cerebral white matter, brainstem, and cerebellum. We report a 4-year-old girl with severe psychomotor delay and horizontal gaze palsy as sequelae of ANE at 17 months of age. The computed tomography showed bilaterally symmetrical low density areas in the thalamus and low density areas in the left middle cerebral artery (MCA) region and the posterior cerebral artery (PCA) region. MRI (T 1-weighted) revealed unevenly distributed small low signal intensity areas with scattered high intensity regions in the thalamus bilaterally. The T2-weighted images showed multiple small low intensity areas around high intensity areas, and low signal intensity areas in the left middle cerebral artery (MCA) region and the posterior cerebral artery (PCA) region. In addition to severe psychomotor delay, the patient exhibited a peculiar eye movements. Horizontal ocular movement was impaired, but vertical ocular movement was almost completely normal. As clearly shown by MRI of the brain, the pontine tegmentum, including bilateral abducens nucleus, paramedian pontine reticular formation (PPRF), medial longitudinal fasciculus (MLF), and the facial nerve were affected, but the thalamo-mesencephalic junction, including the rostral interstitial medial longitudinal fasciculus (riMLF) and the nucleus of Cajal, was spared. To our knowledge, this is the first case of ANE associated with this selective ocular movement disorder ever reported. Because of the multiple symmetrical lesions and pons and the asymmetrical lesions of the MCA and PCA regions in the present case, occlusion of a single vessel could not account for the pathology. The pathophysiological mechanism of ANE is unknown. We postulate that some toxic or vasoactive agent caused vasospasm and subsequent breakdown of the blood-brain barrier, especially in the thalamus and pons, resulting in the unique distribution of the lesions and the rare eye movement disorder observed in the present case.

Brain↗

Tissue factor pathway inhibitor inhibits aortic smooth muscle cell migration induced by tissue factor/factor VIIa complex.

Tissue factor (TF), a transmembrane glycoprotein, forms a high affinity complex with factor VII/VIIa (FVIIa) and thereby initiates blood coagulation. Tissue factor pathway inhibitor (TFPI) is an endogenous protease inhibitor of TF/FVIIa-initiated coagulation. We previously reported that TF was a strong chemotactic factor for cultured vascular smooth muscle cells (SMCs). In this study, we examined the contribution of FVIIa and the effect of TFPI to TF-induced cultured SMC migration. TF/FVIIa complex showed a strong migration ability, however, neither TF alone nor FVIIa induced SMC migration. TF/FVIIa treated by a serine protease inhibitor and the complex of TF and inactivated FVIIa (DEGR-FVIIa) did not stimulate SMC migration. Pretreatment with hirudin and the antibodies to alpha-thrombin and factor X had no effect on TF/FVIIa-induced SMC migration, although alpha-thrombin and factor Xa also induced SMC migration respectively. TFPI markedly inhibited TF/FVIIa-induced SMC migration in a concentration-dependent manner, but did not affect the SMC migration induced by platelet-derived growth factor (PDGF)-BB, basic fibroblast-growth factor (bFGF), or alpha-thrombin. These results indicate that the catalytic activity of TF/FVIIa complex is important on SMC migration, and TFPI can reduce SMC migration as well as thrombosis.

Animals↗

[New aspects in the liver regeneration following partial hepatectomy].

We demonstrated the new two concepts for the liver regeneration after partial hepatectomy (PHx). The first is immunological findings in the regenerating liver. Th1 type T cells, which produce IFN gamma, and extrathymic T cells may play an important role in immunological control system of liver regeneration after PHx on the basis of the cellular immunity restricted by MHC class I and II molecules. The second is the mechanism of "on and off" on liver regeneration after PHx. Portal pressure, which reflecting wall shear stress of sinusoid, may trigger the liver regeneration and control the liver volume after PHx. There are two type of intrahepatic leukocytes; one type would tend to stay associated with SEC, while the other would not. Therefore shear stress may have a great influence on the leukocytes-sinusoidal endothelial cells (SEC) adhesion immediately after partial hepatectomy.

Animals↗

Expression of tissue factor and tissue factor pathway inhibitor in rats lungs with lipopolysaccharide-induced disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a frequent complication of endotoxin shock, and modulation of endothelial cell hemostatic properties has been proposed to play an important role in its onset. We examined the in vivo expression of tissue factor (TF) and TF pathway inhibitor (TFPI) in rat lungs of a lipopolysaccharide (LPS)-induced DIC model. Light and electron microscopic studies showed that fibrin-rich thrombi were present in the pulmonary microvasculature 3 hours after intraperitoneal injection of LPS (7.5 mg/kg) and increased in number at 6 hours. In an immunohistochemical study, an increase in number of monocytes in the microvasculature was observed after LPS injection, and many of these cells (> 90%) were positive for TF antigen. However, no TF expression in endothelial cells was detected. Pulmonary endothelial cells showed positive reaction for TFPI antigen before LPS injection, but TFPI-positive endothelial cells markedly decreased in number after LPS injection. mRNA expression of TF increased and that of TFPI decreased in the lung tissue 3 and 6 hours after LPS injection. High values of TF activity were detected in the lung tissue and plasma, whereas TFPI activities decreased after LPS injection. These results indicate that imbalance between TF and TFPI, overexpression of TF, and underexpression of TFPI in the lung may contribute to thrombus formation in this LPS-induced DIC model.

Animals↗

Competition for tetrahydrobiopterin between phenylalanine hydroxylase and nitric oxide synthase in rat liver.

Tetrahydrobiopterin (BH4) is an important cofactor for two hepatic enzymes, inducible nitric oxide synthase (iNOS) and phenylalanine hydroxylase (PAH), and competition for BH4 between the two enzymes might limit hepatic iNOS or PAH activity. To test this hypothesis, we determined whether conversion of phenylalanine to tyrosine was modified by changes in NO synthase activity, and conversely whether NO synthesis was limited by the rate of phenylalanine conversion to tyrosine in rat hepatocytes and perfused livers. NO production was decreased only slightly, when flux through PAH was maximized in isolated perfused livers, and in isolated hepatocytes only when BH4 synthesis was inhibited. Increases in NO synthesis did not reduce tyrosine formation from phenylalanine. Phenylalanine markedly increased biopterin synthesis, whereas arginine had no effect. Thus, basal BH4 synthesis appears to be adequate to support iNOS activity, whereas BH4 synthesis is increased to support PAH activity.

Animals↗

Double transduction with GTP cyclohydrolase I and tyrosine hydroxylase is necessary for spontaneous synthesis of L-DOPA by primary fibroblasts.

Gene transfer of tyrosine hydroxylase (TH) in animal models of Parkinson's disease (PD), using either genetically modified cells or recombinant virus vectors, has produced partial restoration of behavioral and biochemical deficits. The limited success of this approach may be related to the availability of the cofactor, tetrahydrobiopterin (BH4), because neither the dopamine-depleted striatum nor the cells used for gene transfer possess a sufficient amount of BH4 to support TH activity. To determine the role of BH4 in gene therapy, fibroblast cells transduced with the gene for TH were additionally modified with the gene for GTP cyclohydrolase l; an enzyme critical for BH4 synthesis. In contrast to cells transduced with only TH, doubly transduced fibroblasts spontaneously produced both BH4 and 3, 4-dihydroxy-L-phenylalanine. To examine further the importance of GTP cyclohydrolase I in gene therapy for PD, in vivo micro-dialysis was used to assess the biochemical changes in the dopamine-denervated striatum containing grafts of genetically modified fibroblasts. Only denervated striata grafted with fibro-blasts possessing both TH and GTP cyclohydrolase I genes displayed biochemical restoration. However, no significant differences from controls were observed in apomorphine-induced rotation. This is partly attributable to a limited duration of gene expression in vivo. These differences between fibroblasts transduced with TH alone and those additionally modified with the GTP cyclohydrolase I gene indicate that BH4 is critical for biochemical restoration in a rat model of PD and that GTP cyclohydrolase I is sufficient for production of BH4.

Animals↗