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Biomedical subjects

T Ikegami

Publications and source records attributed to T Ikegami.

At least 73 records · Page 4Linked to original sources

Response of cerebral blood flow and cerebrovascular reactivity to acetazolamide in patients with dementia and idiopathic normal-pressure hydrocephalus.

The responses of cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to administration of acetazolamide were investigated in 16 patients with dementia and ventriculomegaly to clarify the cerebral hemodynamics in patients with idiopathic normal-pressure hydrocephalus (NPH). The mean CBF velocity in the whole brain was measured by the Patlak plot method by using technetium-99m hexamethylpropyleneamine oxime single-photon emission computerized tomography. The CVR values were obtained from the response to administration of 500 mg of acetazolamide and calculated as the percentage of change from the baseline mean CBF value. The mean CBF value was significantly reduced (p < 0.01) in six patients with (35.2 +/- 5 ml/100 g/minute) and 10 patients without (33.5 +/- 2.8 ml/100 g/minute) NPH compared with the age-matched normal controls (40.8 +/- 3.2 ml/100 g/minute), showing no significant difference. The CVR was significantly impaired in patients with NPH (0.8 +/- 1.7%; p < 0.001), whereas in patients without NPH preserved CVR (11.3 +/- 3%) was demonstrated compared with the normal controls (14.7 +/- 1.1%). In patients with NPH a significantly lower CVR (p < 0.001) was shown than in those without NPH. The CVR significantly increased (p < 0.001) after placement of a shunt in patients with NPH. Reductions in both CBF and CVR may be diagnostic indicators of NPH in patients with dementia in whom ventriculomegaly is present. In patients with dementia and idiopathic NPH both reduced CBF and extremely impaired CVR are shown. The results of the present study suggest that ischemia due to the process of NPH is responsible for the reduction of CBF and manifestation of symptoms in patients with idiopathic NPH.

Journal Article↗

Preparation of uniformly sized polymeric separation media potentially suitable for small-scale high-performance liquid chromatography and/or capillary electrochromatography.

Uniformly sized polymer particles were prepared by either a two-step swelling and polymerization method or a Shirasu porous glass (SPG) emulsification technique to compare their suitability as a uniformly sized packing material for small-scale high-performance liquid chromatography (HPLC) or capillary electrochromatography (CEC). The SPG emulsification technique afforded slightly worse size uniformity compared to the two-step swelling and polymerization technique. However, fairly nice spherical shapes with reproducible outward appearance and internal pore size distribution were obtained for both of 3- or 6-micron sized particles. On the other hand, the two-step swelling and polymerization method afforded broken particles with quite different outward appearances due to the polymeric porogen effects of seed polymer utilized as the shape template. In HPLC, the column packed with the 3-micron particles prepared with the SPG emulsification technique proved to have a fairly high column efficiency with good column stability, as assessed under repeated use in gradient elution. On the other hand, the column packed with the packing material obtained through the two-step swelling and polymerization method showed much poorer column stability, while initial column efficiency was compatible to that obtained using the SPG emulsification method. In addition, the packing material prepared with the SPG emulsification technique could be modified with ion-exchangeable monomers and showed fairly good column efficiency in the CEC mode.

Chromatography, High Pressure Liquid↗

Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure.

The prognosis for patients with fulminant (FHF) or subfulminant hepatic failure (SFHF) has improved since the introduction of liver transplantation. However, the death rate of patients awaiting liver transplantation is high, possibly because of the difficulty in obtaining grafts in a timely manner, given the relative shortage of cadaveric donors. Between June 1990 and June 1999, 106 patients underwent living-related liver transplantation (LRLT) at Shinshu University Hospital. Among them, 8 patients had FHF and 6 had SFHF; these 14 patients are the subjects of this report. The graft volumes (GV) ranged from 231 mL to 625 mL, corresponding to 35% to 105% of the recipients' standard liver volume (SLV). The postoperative courses of all donors were uneventful. Following liver transplantation, all grafts functioned favorably, with normalization of serum total bilirubin within 3 to 5 days and normalization of coagulation profiles within 4 to 7 days. Thirteen of the 14 recipients are still alive. The actuarial 6-month, 1-year, and 5-year survival rates were 100%, 90%, and 90%, respectively. In the present study, when the ratio of the GV to the recipient's SLV was more than 35%, the graft was able to support the patient's metabolic demand after liver transplantation for FHF or SFHF. Because of the urgent nature of liver transplantation in this clinical condition, concerns over informed consent may be even greater than for elective LRLT. Nevertheless, the high success rate and low donor risk may justify this option for pediatric patients, as well as for a limited population of adult patients suffering from FHF or SFHF.

Adolescent↗

Effects of peritumoural oedema on cerebral blood flow and cerebrovascular reactivity in patients with alert consciousness.

The effects of peritumoural oedema on cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were studied in 18 patients with alert consciousness. Hemispheric mean CBF was measured by performing first-pass radionuclide angiography using technetium-99m hexamethylpropylene amine oxime. CVR was measured as the percentage change from the baseline mean CBF value after acetazolamide administration. Patients were classified into three groups according to the severity of peritumoural oedema. The mean CBF of both hemispheres in each group was not significantly different from that of age-matched controls. CVR was preserved in patients with mild peritumoural oedema (n=6), but was significantly (P<0.01) reduced in patients with moderate (n=7) and severe peritumoural oedema (n=5). No significant correlation was found between the degree of midline shift and the mean CVR of both hemispheres (P=0.09). Surgical removal of the tumour significantly (P<0.05) improved the impaired CVR, although the mean CBF did not change. Administration of glucocorticoid improved the impaired CVR, without a change in the mean CBF, in a patient with a metastatic brain tumour. We conclude that CVR is impaired by the development of peritumoural oedema prior to changes in mean CBF.

Acetazolamide↗

First case of cadaveric liver transplantation in Japan.

The first case of liver transplantation from a brain-dead donor in Japan is described. The recipient was a 43-year-old man with familial amyloid polyneuropathy who manifested various neuropathic symptoms and autonomic dysfunction at the time of transplantation. The graft had three arteries, for which a single trunk was created at the back table. A side-to-side cavacaval anastomosis was performed as an outflow reconstruction. To avoid portal congestion, a temporary shunt between the right posterior branch of the portal vein and the vena cava was constructed, instead of a venovenous bypass. The graft preservation time was 7.2 h and the operation time was 12.2 h. Although sufficient blood flow in the hepatic artery, portal vein, and hepatic vein was confirmed intra- and postoperatively, using Doppler ultrasound, transient graft dysfunction was observed immediately after surgery, but there was spontaneous improvement. The patient was discharged 100 days after transplantation.

Adult↗

Additional microvascular anastomosis in reconstruction after total esophagectomy for cervical esophageal carcinoma.

BACKGROUND: Maintaining sufficient blood flow to the substitute organ after total esophagectomy is essential for decreasing the risk of anastomotic leakage. Additional venous, or arterial and venous, anastomoses between the vessels of the gastric tube and the vessels in the neck after total esophagectomy are described for 11 patients with cervical esophageal carcinoma. METHODS: The tissue blood flow was measured by laser Doppler flowmetry before and after anastomosis. Venous anastomosis was performed for all 11 patients, and arterial anastomosis was added for 7 patients. RESULTS: A significant increase in tissue blood flow was observed after venous anastomosis alone (mean, 19%; P < 0.05) and after arterial and venous anastomoses (mean 43%; P < 0.01). There was no anastomotic leakage or hospital death. CONCLUSIONS: This procedure may reduce the risk of anastomotic leakage especially in the case of pharyngogastrostomy following total esophagectomy.

Anastomosis, Surgical↗

Intermittent jaundice in patients with acute leukaemia: a common mutation of the bilirubin uridine-diphosphate glucuronosyltransferase gene among Asians.

The Gly71Arg mutation of the hepatic bilirubin UDP glucuronosyl-transferase (B-UGT) gene associated with Gilbert syndrome prevails among Japanese and its gene frequency is 0.13. Among 20 patients with acute leukaemia, 4 patients showed intermittent unconjugated hyperbilirubinaemia during the course of combined chemotherapy. The Gly71Arg mutation was detected in all 4 patients with hyperbilirubinaemia, but was not found in 16 patients without hyperbilirubinaemia. Two of them were heterozygotes and one was a homozygote for the Gly71Arg mutation, and the other was a compound heterozygote of the Gly71Arg mutation and TA insertion mutation in the TATA box of the B-UGT gene. In addition to the complications leading to hyperbilirubinaemia, including liver damage due to drugs, viral infections or tumour cell infiltrations and alloimmune haemolysis, carrier status for the Gly71Arg mutation should be considered in a patient with leukaemia showing intermittent hyperbilirubinaemia during the course of chemotherapy, especially among Japanese, Koreans and Chinese owing to its prevalence in those populations.

Acute Disease↗

Resonance assignments, secondary structure and 15N relaxation data of the human transcriptional coactivator hMBF1 (57-148).

Multiprotein bridging factor 1 (MBF1) is a transcriptional coactivator that is thought to bridge between the TATA box-binding protein (TBP) and DNA binding regulatory factors, and is conserved from yeast to human. Human MBF1 (hMBF1) can bind to TBP and to the nuclear receptor Ad4BP, and is suggested to mediate Ad4BP-dependent transcriptional activation. Here we report the resonance assignments and secondary structure of hMBF1 (57-148) that contains both TBP binding and activator binding residues. 15N relaxation data were also obtained. As a result, hMBF1 (57-148) was shown to consist of flexible N-terminal residues and a C-terminal domain. The C-terminal domain contains four helices and a conserved C-terminal region.

Amino Acid Sequence↗

Identification of the core domain and the secondary structure of the transcriptional coactivator MBF1.

BACKGROUND: Multiprotein bridging factor 1 (MBF1) is a transcriptional coactivator necessary for transcriptional activation caused by DNA binding activators, such as FTZ-F1 and GCN4. MBF1 bridges the DNA-binding regions of these activators and the TATA-box binding protein (TBP), suggesting that MBF1 functions by recruiting TBP to promoters where the activators are bound. In addition, MBF1 stimulates DNA binding activities of the activators to their recognition sites. To date, little is known about structures of coactivators that bind to TBP. RESULTS: The two-dimensional (2D) 1H-15N correlation spectrum of 15N labeled MBF1 indicated that MBF1 consists of both flexible and well structured parts. Limited digestion of MBF1 by alpha-chymotrypsin yielded a approximately 9 kDa fragment. N-terminal sequence analysis and NMR measurements revealed that this fragment originates from the C-terminal 80 residues of MBF1 and form a well structured C-terminal domain of MBF1, MBF1CTD. As previous deletion analyses have shown that MBF1CTD is capable of binding to TBP, it is suggested that MBF1CTD is the TBP binding domain of MBF1. Sequential assignments have been obtained by means of three-dimensional (3D) and four dimensional (4D) heteronuclear correlation spectroscopies, and then the secondary structure of MBF1CTD was determined. As a result, MBF1CTD was shown to contain four amphipathic helices and a conserved C-terminal region. Asp106 which is assumed to be responsible for the binding to TBP is located at the hydrophilic side of the third helix. CONCLUSIONS: Structural analyses revealed that MBF1 consists of two structurally different domains. A N-terminal region is indispensable for the binding to activators, and does not form a well defined structure. In contrast, the C-terminal 80 residues, which is capable of binding to TBP by itself, form a well-structured domain, MBF1CTD. MBF1CTD is made up of four amphipathic helices and a conserved C-terminal tail. A putative TBP binding residue is located on the hydrophilic surface of the third helix.

Amino Acid Sequence↗

Metal ion-directed DNA recognition by chelating DNA ligands.

Novel DNA ligand bearing oxine and pyridinium group has been synthesized. The DNA binding of this ligand was regulated by coexisting Cu2+ over the range of more than three orders in magnitude of binding constant. This should be due to the metal-mediated dimerization of the ligand and concomitant emergence of cationic charges. There were definite two DNA binding modes for the ligand dimer depending on the P/L ratio.

Chelating Agents↗

Resonance assignments, solution structure, and backbone dynamics of the DNA- and RPA-binding domain of human repair factor XPA.

XPA is involved in the damage recognition step of nucleotide excision repair (NER). XPA binds to other repair factors, and acts as a key element in NER complex formation. The central domain of human repair factor XPA (residues Met98 to Phe219) is responsible for the preferential binding to damaged DNA and to replication protein A (RPA). The domain consists of a zinc-containing subdomain with a compact globular structure and a C-terminal subdomain with a positively charged cleft in a novel alpha/beta structure. The resonance assignments and backbone dynamics of the central domain of human XPA were studied by multidimensional heteronuclear NMR methods. 15N relaxation data were obtained at two static magnetic fields, and analyzed by means of the model-free formalism under the assumption of isotropic or anisotropic rotational diffusion. In addition, exchange contributions were estimated by analysis of the spectral density function at zero frequency. The results show that the domain exhibits a rotational diffusion anisotropy (Dparallel/Dperpendicular) of 1.38, and that most of the flexible regions exist on the DNA binding surface in the cleft in the C-terminal subdomain. This flexibility may be involved in the interactions of XPA with various kinds of damaged DNA.

Binding Sites↗

Cerebral blood flow in patients with normal pressure hydrocephalus.

Mean cerebral blood flow (CBF) of the whole brain was measured in 48 patients who underwent cerebrospinal fluid shunt surgery for normal pressure hydrocephalus (NPH) by performing first-pass radionuclide angiography using 99Tcm-hexamethylpropylene amine oxime. Patients were divided according to outcome into an 'excellent' improvement group, a 'good' improvement group, a 'fair' improvement group and a 'poor' improvement group. Patients with excellent and good improvement had a preoperative mean CBF of 40.4 +/- 3.9 ml.100 g-1.min-1 and 37.1 +/- 5.5 ml.100 g-1.min-1, respectively, both of which were significantly (P < 0.005) higher than that in 11 patients who showed fair improvement (30.8 +/- 3.2 ml.100 g-1.min-1) and six patients who showed poor improvement (31.8 +/- 2.5 ml.100 g-1.min-1). Patients with a clinical improvement after shunting had an increased postoperative mean CBF. We conclude that patients with a preoperative mean CBF of over 35 ml.100 g-1.min-1 can show favourable improvement after a shunting procedure, and that the preoperative mean CBF of 32 ml.100 g-1.min-1 can be considered the critical level for treatment.

Adult↗

Naturally occurring Tyzzer's disease in a calf.

Naturally occurring Clostridium piliforme infection (Tyzzer's disease) was found in a calf. Light microscopic examination revealed multifocal coagulative necrosis in the liver, catarrhal gastroenteritis, tracheitis and pneumonia, and thymic atrophy. Warthin-Starry staining clearly showed large filamentous bacilli in bundles or criss-cross patterns within the hepatocytes and epithelium and smooth muscle cells of the ileum and cecum. Immunohistochemistry using anti-C. piliforme RT and MSK strain antisera showed positive reaction against the bacilli. Electron microscopic examination revealed bacilli within the hepatocytes that demonstrated a characteristic vegetative form, with peritrichous flagella, and spores. The polymerase chain reaction (PCR) study using the paraffin-embedded liver sections, the 196-bp DNA fragment specific to 16S ribosomal RNA of C. piliforme was amplified. The characteristics of these bacilli are consistent with those of of C. piliforme. The PCR technique using paraffin-embedded sections should be useful for confirming C. piliforme infection in spontaneous cases.

Animals↗

Enterocolitis associated with dual infection by Clostridium piliforme and feline panleukopenia virus in three kittens.

Dual infection by Clostridium piliforme and feline panleukopenia virus (FPLV) was found in three kittens. In all cases, we found focal necrosis and desquamation of epithelial cells with occasional neutrophil infiltration in the large intestine. Large filamentous bacilli and spores were observed in the epithelium by using the Warthin-Starry method. Electron microscopy revealed the vegetative forms with characteristic peritrichous flagella and spore forms. Immunohistochemically, these bacilli showed a positive reaction with mouse antisera against the RT and MSK C. piliforme strains. Polymerase chain reaction (PCR) using cecum specimens demonstrated the 196-bp band specific to C. piliforme 16S rRNA. All three kittens were also diagnosed as FPLV-infected on the basis of the characteristic mucosal lesions, including intranuclear inclusions and PCR study for the FPLV genomic DNA. The PCR techniques are useful for confirming the C. piliforme and FPLV infection in spontaneous cases.

Animals↗

Deletion and nonsense mutations of the connexin 32 gene associated with Charcot-Marie-Tooth disease.

Two patients with a mild to moderate phenotype of Charcot-Marie-Tooth disease were identified to carry the mutations of the connexin (Cx) 32 gene. One of the patient had a novel nonsense mutation of tryptophan at amino acid 132 and the other had a deletion of the Cx 32 gene. Our study indicated that a loss of Cx 32 function contributes to a major pathogenesis of X-linked Charcot-Marie-Tooth disease.

Adult↗