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Biomedical subjects

H Mizuno

Publications and source records attributed to H Mizuno.

At least 145 records · Page 8Linked to original sources

Escherichia coli phosphorylates 1,5-Anhydroglucitol and releases 1,5-Anhydroglucitol 6-phosphate when glucose is absent in the medium.

The cyclic polyol 1,5-anhydro-D-glucitol (AG) is detected in most organisms, but little is known about its metabolism and physiological roles. Our previous study demonstrated that Escherichia coli C600 synthesizes AG when glucose is exhausted in the medium and that it temporarily releases AG into and then takes it back from the medium, thus forming a sharp peak in AG concentration in the medium a few hours after reaching stationary growth phase. The present study demonstrates that when glucose is absent in the culture medium, E. coli C600 takes up and phosphorylates AG and releases a large portion of it back into the medium in the form of a phosphate ester. [U-13C]AG was added to the medium after the exhaustion of glucose and the resulting [U-13C]AG phosphate was partially purified by several steps of anion exchange chromatography and identified as AG 6-phosphate by 13C-NMR. The identity of the phosphate ester was also confirmed by GC-MS analysis after further purification.

Binding Sites↗

NMR of all-carbon-13 sugars: an application in development of an analytical method for a novel natural sugar, 1,5-anhydrofructose.

Of the all-carbon-13 compounds, glucose is one of the most easily accessible, and therefore we applied 13C-NMR technique to the metabolic study of glucose-related compounds, 1,5-anhydro-D-glucitol and 1,5-anhydro-D-fructose (AF). Applying an INADEQUATE method to the substitutes of these novel sugars fully labeled with carbon-13, we could trace out the entire carbon skeleton with high sensitivity and confirm the chemical structures of these sugars. The method also provided a much easier way to optimize the enzymatic oxidation for AF preparation: we selectively and continuously monitored the quantities, as well as their structures in aqueous solution, of the substrate and products in a noninvasive manner. Similarly relying upon information from the 13C-NMR, we developed a valuable derivatization method of AF for its GC-MS application, which was so sensitive that we were able to demonstrate the natural occurrence of AF in rat liver.

Animals↗

In vitro evaluation of linear motor-driven total artificial heart.

This paper deals with the in vitro evaluation of a newly developed linear motor-driven total artificial heart (linear TAH). The linear TAHs have been developed and evaluated in mock testing and acute animal experiments. The new linear TAH was made based on experience with acute animal experiments. The maximum static thrust of the new linear pulse motor is 146 N with exciting current of 1.69 A. The weight and the volume of this linear TAH are 1.9 kg and 560 ml, respectively. The linear TAH has a kinetic thrust of 85 to 43 N and provides the maximum flow rate of 6.8 L/min in mock circulatory testing.

Animals↗

[Diagnosis and surgical treatment of metastatic lung tumors].

To investigate the chance of discovery of metastatic lung tumors and the five-year survival rates of patients undergoing surgical resection, we followed 99 patients who underwent initial surgical treatment at our hospital between 1979 and 1996. With regard to primary organs or sites, 32 patients had rectal cancer, 27 patients had breast cancer, 19 patients had colon cancer and 21 patients had osteosarcoma. For 22 of 99 patients (22%), discovery was due to subjective symptoms such as cough and sputum (n = 12), chest (or back) pain (n = 7) or hemosputum (n = 5). Ten of 19 patients (53%) with colon cancer experienced subjective symptoms which led to the discovery of metastases. In 76 of 99 patients (78%), metastatic lung lesions were not discovered through subjective symptoms. In 63 of those 76 patients, such lesions were initially found by plain chest roentgenography or CT. In 20 of 21 patients (95%) who had osteosarcoma, metastatic lung tumors were discovered by chest roentgenography or CT. In 14 of 76 patients, all of whom had metastatic lung carcinomas, the lesions were discovered through elevated levels of tumor markers. Therefore the importance of periodic chest roentgenography and tumor marker testing was demonstrated. Disease-free interval (DFI) was over six years in five of 32 patients (16%) with rectal cancer and 13 of 27 (48%) with breast cancer. DFI was less than five years for 15 of 19 patients (79%) with colon cancer, and less than two years for 16 of 21 (75%) with osteosarcoma. Thus, DFI differed according to the sites of the tumors. The five-year survival rates of 97 patients were examined. Patients were divided according to the sites of their primary tumors, and then subdivided according to the type of surgery they received. Patients were thus divided into five categories: I) those who underwent incomplete resection of metastatic lung lesions, II) those who underwent complete resection of both pulmonary lesions and involved mediastinal lymph nodes, III) those who had undergone previous treatment for tumors in organs other than the lung, IV) those who underwent complete resection of multiple lung lesions, and V) those who underwent complete resection of solitary lung lesions. For all primary sites, none of the patients in group I) survived for more than two years. Therefore complete resection seems very important for the treatment of metastatic lung tumors. With regard to the other groups, several facts were noted. For rectal cancer, the five-year survival rate of groups V) and III) was 55.6% in either case. Therefore complete resection of rectal cancer metastatic to the lung may improve the five-year survival rate even for patients who have previously been treated for cancers in organs other than the lung. For colon cancer, the five-year survival rate of group V) was 51.4%. Complete resection of only a solitary lung lesion may improve the five-year survival rate for colon cancer. For breast cancer, the five-year survival rate of group V) was 37.5% and that of group II) was 60.0%. This may indicate that for patients who have both pulmonary lesions and mediastinal lymph node involvement, complete resection of both is important. For osteosarcoma the five-year survival rate of group IV) was 26.0%. Thus, osteosarcoma patients have a chance of survival if they undergo complete resection of lung metastases.

Adolescent↗

[Self-expanding nitinol stents for treatment of tracheobronchial and esophageal stenosis caused by lung cancer].

A 57-year-old man was admitted because of dysphagia. Two year earlier, endoscopic ND-YAG laser treatment had been performed for squamous cell carcinoma of the tracheal carina. The esophagus was compressed and narrowed by invasion of lung cancer. After ballooning, under endoscopic and fluoroscopic control, a self-expanding nitinol stent (SENS, Ultraflex, Microvasive) was implanted in the esophagus. Immediately after esophageal prosthesis implantation, severe dyspnea and stridor developed because of tumor strictures in the left main bronchus. Under fluoroscopic and guide-wire control, SENS (Accuflex, Microvasive) was implanted in the tracheobronchial tree. Dyspnea, dysphagia and stridor were markedly improved after placement of two nitinol stents. Highly flexible, knitted, self-expanding nitinol stent is made of a nickel titanium alloy. Although the implantation of SENS in tracheobronchial stenosis has not previously been reported, it should be useful for prevention of airway obstruction.

Alloys↗

Molecular cloning and structural characterization of the human histidase gene (HAL).

Histidase (EC 4.3.1.3) is a cytosolic enzyme that catalyzes the nonoxidative deamination of histidine to urocanic acid. Histidinemia, resulting from reduced histidase activity as reported in Cambridge stock his/his mice and in humans, is the most frequent inborn metabolic error in Japan. The histidase chromosomal gene (HAL) was isolated from a lambda EMBL-3 human genomic library using the human histidase cDNA as a probe. Restriction mapping and Southern blot analysis of the isolated clones reveal a single-copy gene spanning approximately 25 kb and consisting of 21 exons. Exon 1 encodes only 5' untranslated sequence of liver histidase mRNA, with protein coding beginning in exon 2. A rarely observed 5' GC, similar to that reported in the human P-450 (SCC) gene, is present in intron 20. All other splicing junctions adhere to the canonical GT/AG rule. A TATA box sequence is located 25 bp upstream of the liver histidase transcription initiation site determined by S1 nuclease protection analysis. Several liver- and epidermis-specific transcription factor binding sites, including C/EBP, NFIL6, HNF5, AP2/KER1, MNF, and others, are also identified in the 5' flanking region. Consistent with the hepatic and epidermal expression of histidase, this finding suggests that histidase transcription may be regulated by these factors. We further identify a polymorphism (A to G transition) in the histidase coding region of exon 16. The human histidase genomic structure presented here should facilitate the molecular investigation of symptomatic and asymptomatic forms of histidinemia.

Alternative Splicing↗

Surgical treatment of small cell carcinoma of the lung: advantage of preoperative chemotherapy.

To assess the effect of chemotherapy on postoperative survival of patients with small cell lung carcinoma (SCLC), 46 patients who underwent surgery at Kyoto University between 1976 and 1991 were retrospectively reviewed. Seventeen patients (37.0%) received chemotherapy prior to as well as after surgery (neoadjuvant therapy group), 23 (50.5%) received chemotherapy only after surgery (adjuvant therapy group), and the other six received no chemotherapy (non-chemotherapy group). The 5-year survival rate of patients with c-Stage I or II disease in the neoadjuvant therapy group was as high as 80.0%, which seemed to be higher, although with no statistical significance, than that in the adjuvant therapy group (37.7%, P = 0.10). The 5-year survival rate of patients with c-Stage III (IIIa or IIIb) disease in the neoadjuvant therapy group, although not satisfactory (10.0%), was significantly higher than that in the adjuvant therapy group (0.0%, P = 0.04). No patients in the non-chemotherapy group had survived 5 years. Moreover, multivariate analysis showed that failure to employ preoperative chemotherapy was the strongest prognostic factor causing a poor prognosis (P = 0.01). On the other hand, eight (30.8%) out of 26 patients with c-Stage I or II disease postoperatively proved to have mediastinal lymph node involvement (pN2-3), and two (7.7%) proved to have intrapulmonary metastasis (PM). Considering the advantage of preoperative chemotherapy and the discrepancy between c- and p-stage, sufficient chemotherapy prior to surgery should be employed, and may realize a good prognosis in patients with c-Stage I or II disease. In contrast, patients with c-Stage III disease are not appropriate as candidates for surgery even if preoperative chemotherapy is performed.

Aged↗

Treatment of Pancoast tumors. Combined irradiation and radical resection.

Eighteen patients underwent combined preoperative irradiation and radical resection for a Pancoast tumor at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1977 and 1993. Four patients were applied a full radiation dose of 50-70 Gy and fourteen patients were applied a reduced dose of 33-40 Gy preoperatively. Eleven of these fourteen were applied a supplemental dose postoperatively up to a total dose of at least 50 Gy. Fourteen lobectomies, three partial resections, and one pneumonectomy were performed with combined resection of chest wall or adjacent structures: rib in 14, vertebra in 4, brachiocephalic vein in 3, subclavian artery in 2, spinal nerve in 3, sympathetic truncus in 2, phrenic nerve in 2 cases. Chest walls were reconstructed with marlex mesh in 5 patients, and two subclavian arteries and one brachiocephalic vein were repaired with artificial grafts. In 13 patients complete resections were achieved, but in the other 5 only incomplete resections leaving residual tumor were achieved. Incomplete resections consisted of 4 positive stumps at the brachial plexus of the apex and one aortic involvement by a metastatic lymph node. There was one operative death. Median survival was 21.6 months and the 5-year-survival rate was 38.5% for all 18 patients. In the complete resection group 5-year-survival was 56.4%, but in the incomplete-resection group 0%, showing a significantly more favorable result for the complete resection group. It is considered that evidence of incomplete resection influences the prognosis and that particularly tumor invasion to the brachial plexus may serve as a limiting factor for surgery.

Adult↗

Pulmonary metastasis of polymorphous low-grade adenocarcinoma of the minor salivary gland.

A surgical case of pulmonary metastases of polymorphous low-grade adenocarcinoma (PLGA) originating from the minor salivary gland in the soft palate in a 62-year-old woman is reported. PLGA has been to be a locally invasive carcinoma without distant metastases; thus our case is the first reported case with histologically-proven distant metastases to the lung. We emphasise that attention should be paid to distant metastases especially to the lung even in case of PLGA.

Adenocarcinoma↗

Purification and properties of L-galactono-gamma-lactone dehydrogenase, a key enzyme for ascorbic acid biosynthesis, from sweet potato roots.

L-Galactono-gamma-lactone dehydrogenase (L-galactono-gamma-lactone:ferricytochrome c oxidoreductase [EC 1.3.2.3], GLDHase) which catalyzes the terminal step in the biosynthesis of L-ascorbic acid (AsA) has been purified from roots of sweet potato (Ipomoea batatas L., cv. Kintoki). Highly purified preparation of the GLDHase was obtained by three column chromatography steps with a recovery of ca. 1%, after solubilization from mitochondria in sweet potato roots. SDS-PAGE exhibited a single band at 56 kDa. In the native state, the apparent molecular mass of the enzyme was 56 kDa, based on a Sephadex G-100 gel filtration. The pI and optimum pH values were 5.8 and 7.9, respectively. The Km value for L-galactono-gamma-lactone was 0.12 mM. Substrate inhibition was obtained at concentrations greater than 4.2 mM. The enzyme was inhibited by p-chloromercuribenzoate (PCMB) and acriflavine, and the inhibition of acriflavine was diminished by the addition of FAD or FMN. The only effective substrate for the GLDHase was L-galactono-gamma-lactone.

Ascorbic Acid↗

Phosphorylation of 1,5-anhydro-D-glucitol in mammalian cells.

A cyclic polyol, 1,5-anhydro-D-glucitol (AG), is generally present in animals, although little is known about the metabolic and physiological roles of AG in any type of animal cells. The present metabolic study demonstrated phosphorylation of AG in human chronic myelogenous leukemia cells, K-562. Phosphorylated AG (AGP) was also proved to be present in various rat organs; its level in most organs ranged between 2 and 5 nmol/g wet tissue, which amounted to 5 to 10% of the AG levels in the respective organs. In the spleen and brain, however, the AGP levels were especially high, 13.4 and 8.3 nmol/g, respectively, or 24.4 and 20.6% of the respective AG levels. These data suggest that AGP is an intermediary metabolite related to AG in animal cells.

Animals↗

Expression of vascular permeability factor (VPF/VEGF) messenger RNA by plasma cells: possible involvement in the development of edema in chronic inflammation.

Edema occurs in some types of chronic inflammation such as nasal polyps, uterine cervical polyps and gastric hyperplastic polyps. However, the factors or cellular components involved in the development of edema in chronic inflammation remain to be clarified. Recently, the gene encoding vascular permeability factor (VPF) or vascular endothelial growth factor (VEGF) and the genes encoding its receptors (kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase-1 [fit-1]) have been cloned. VPF/VEGF induces vascular hyperpermeability and vascular endothelial proliferation through KDR or fit-1 receptors. As there is a possibility that VPF/VEGF may play a role in the development of edema in chronic inflammation, we examined the messenger (m) RNA expression of VPF/VEGF and its receptors in nasal polyp tissues, which is an example of chronic inflammation with remarkable edema. Using northern blotting, all nasal polyp tissues examined expressed mRNA of VPF/VEGF and KDR. In situ hybridization revealed that VPF/VEGF mRNA-expressing cells were scattered in the edematous stroma of nasal polyps. In the adjacent sections, these cells showed the morphological features of plasma cells and expressed mRNA of immunoglobulin light chains. Human B cell leukemia and plasmacytoma cell lines expressed VPF/VEGF mRNA but human mast-cell leukemia and T cell leukemia cell lines did not. The alternatively spliced pattern of VPF/VEGF transcripts observed in nasal polyp tissues was consistent with that in plasmacytoma cell lines. Taken together, the VPF/VEGF mRNA-expressing cells in nasal polyps appeared to be plasma cells, suggesting that plasma cells may play an important role in the development of edema in chronic inflammation through the production of VPF/VEGF.

Base Sequence↗

Magnetic resonance imaging for the diagnosis of prostate cancer metastatic to bone.

OBJECTIVE: To examine the role of magnetic resonance imaging (MRI) in the evaluation of osseous metastasis in patients with prostate cancer. PATIENTS AND METHODS: A series of 36 patients with known prostate cancer, who were undergoing MRI and an isotope bone scan, were studied. RESULTS: Of 19 positive bone scans, MRI was read as negative for metastasis in one. Of eight equivocal scans, two MR images were interpreted as positive and six as negative. Of nine negative scans MRI was positive in one. Further MRI demonstrated additional metastatic lesions that were not shown by bone scintigraphy in six patients. MRI clearly indicated the areas of spinal cord compression in five patients with spinal metastases and associated myelopathy. CONCLUSION: MRI is helpful in the diagnosis of metastatic prostate cancer, especially when other radiographic examinations are inconclusive or spinal cord compression is suspected.

Bone Neoplasms↗

[Surgical treatment of apical invading lung cancer].

Operative technique and long-term results of seventeen patients with apical invading lung cancers were evaluated. External radiation therapy was administered preoperatively in all but one. Thirteen lobectomies, three wedge resections and one pneumonectomy were performed with combined resections of chest wall (and adjacent structures) 12, vertebra 3, brachicephalic vein 2, subclavian artery 1, lower part of brachial plexsus 3, sympathetic trunk 2 and phrenic nerve 1. Chest walls were reconstructed with marlex meshes in 5, the subclavian artery and one brachiocephalic vein were with artificial grafts. Operations were considered relative curative in 10, relative non-curative in 2 and absolutely non-curative in 5. Absolutely non-curative operations were due to cancer-positive stump of brachial plexus in the apex in four and metastatic lymph node invading aorta in one. Over all five-year survival rate was 35.3% and median survival was 20 months. Five-year survivals in patients with curative operations and non-curative operations were 60% and 0%, respectively, and the former was significantly higher. Surgical margin is a large factor for long-term result and invasion to the brachial plexus is thought to be a limiting factor for surgery.

Adult↗

[Object analysis of bone marrow MR imaging using double echo STIR sequence in hematological diseases].

The bone marrow of 84 patients with hematological disorders was investigated using short inversion time inversion recovery sequence (STIR) on an 1.5 Tesla superconducting MRI system. Double echo times of 20 and 100msec were applied to research the signal characteristics of the lesion and carry out quantitative analysis of the receiver operating characteristic curve (ROC). The hematological diseases included 19 cases of myelodysplastic syndrome (MDS), 18 of multiple myeloma (MM), 18 of chronic myelocytic leukemia (CML), 9 of aplastic anemia (AA), 8 of acute myelocytic leukemia (AML), 3 of chronic lymphocytic leukemia (CLL), 3 of myelofibrosis, and 3 others. Using STIR with double echo times, bone marrow showed high signal intensity (SI) on short TE and low SI on long TE in MDS and CML; high SI on short and long TE in myelofibrosis and CLL; high SI on short TE and high to moderately high SI on long TE in MM; and low SI on short and long TE in AA. Quantitative analysis of 33 patients showed high sensitivity and specificity in AA (81% and 94%, respectively) and moderate sensitivity and high specificity in MM (61%, 88%). CML and MDS were similar with low sensitivities (40%, 41%) and high specificities (80%, 78%). Differential diagnosis between CML and MDS was difficult using STIR with the double echo time method.

Adolescent↗

[MR imaging of temporomandibular joint (TMJ): mandibular fracture and traumatic disk injury].

Using an 1.5 Tesla superconducting MR unit and surface coil, 12 mandibular fracture patients were evaluated for TMJ disk change. Sagittal and coronal images of the TMJ with a slice thickness of 2mm were obtained with FISP 2D or 3D. TR = 30 msec, TE = 12 msec, and flip angle = 40 degrees were applied. Among 12 patients, FISP 3D revealed increased signal intensity of the disk in 70% of cases. Traumatic fluid collection at or adjacent to the TMJ showed high intensity. The disk was displaced anteromedially regardless of the site of fracture.

Adolescent↗