Biomedical subjects
Publications and source records attributed to K Mizuguchi.
An extremely rare case of solitary fibrous tumor of the prostate is presented. The patient underwent a radical retropubic prostatectomy and has remained well with no evidence of recurrence during the last 18 months. This is the fifth reported case of such a lesion arising in the prostate.
In hypothermic cardiopulmonary bypass (CPB), various vasodilators are used to control the perfusion pressure. These agents, however, often decrease the pressure excessively, and the low perfusion pressure may persist until the end of CPB. In this study we evaluate the safety and characteristics of the regulation of perfusion pressure during CPB using a volatile anesthetic, sevoflurane which has an extremely low partition coefficient. Twenty adult patients who underwent cardiac surgery were studied. Sevoflurane was applied by a vaporizer inserted into the oxygenator gas supply line. Pump flows were fixed at 2.4 L/min/m2 during the hypothermic period. Sevoflurane concentration was adjusted to keep mean arterial pressure (MAP) between 40 and 70 mmHg during CPB. Hemodynamic and metabolic parameters were measured and compared to the group we previously treated with chlorpromazine. In all cases, MAP could be maintained adequately. In the sevoflurane group, systemic vascular resistance indices (SVRI) during the rewarming period and at the end of CPB were higher, and doses of norepinephrine needed at the end of CPB were significantly lower than in the chlorpromazine group. The regulation of perfusion pressure during CPB using sevoflurane was safe and could easily maintain adequate SVRI.
The voltage-sensitive sodium channel confers electrical excitability on neurons, a fundamental property required for higher processes including cognition. The ion-conducting alpha-subunit of the channel is regulated by two known auxiliary subunits, beta1 and beta2. We have identified rat and human forms of an additional subunit, beta3. It is most closely related to beta1 and is the product of a separate gene localized to human chromosome 11q23.3. When expressed in Xenopus oocytes, beta3 inactivates sodium channel opening more slowly than beta1 does. Structural modeling has identified an amino acid residue in the putative alpha-subunit binding site of beta3 that may play a role in this difference. The expression of beta3 within the central nervous system differs significantly from beta1. Our results strongly suggest that beta3 performs a distinct neurophysiological function.
A sequence similarity search of the Drosophila nucleotide database using vertebrate amphiphysin as a query identified a cDNA that encodes a Drosophila amphiphysin. The predicted protein has conserved sequence domains that should enable it to dimerise and bind to dynamin. Structural modelling suggests that the Src-homology-3 (SH3) domains of vertebrate and Drosophila amphiphysins are highly similar, supporting the putative ability of the latter to bind dynamin. However, the fly amphiphysin shows less conservation to sequences in the vertebrate amphiphysins that bind other endocytic components such as clathrin, AP-2 and endophilin. Amphiphysin is a single-copy gene that maps to position 49B on polytene chromosomes. Messenger RNA of this amphiphysin is expressed widely during embryogenesis and has elevated expression in a number of sites including the foregut, hindgut and epidermis, but not in the central nervous system. Taken together, these data are consistent with a role for Drosophila amphiphysin in endocytosis, but the details of this role may differ from that of vertebrate amphiphysins.
BACKGROUND: Gene guns have been used to transfer genes into various organs, but there has been no report of successful gene gun-mediated gene transfer into the heart. In this study, we assessed the possibility of gene therapy using a gene gun and an episomal plasmid vector. METHODS: Gene transfer was performed using two sizes of gold particles and two plasmids (an episomal vector and a conventional plasmid vector). From the first to eighth week after the bombardment, rats were sacrificed. The excised hearts were subjected to X-gal staining and histologic examination. To ensure that plasmid was not distributed to organs other than the heart, the presence of the beta-gal sequence was examined by polymerase chain reaction analyses. RESULTS: Gene expression persisted for 6 weeks. The episomal vector apparently contributed to long-lasting expression. Infiltration of monocytes or leukocytes was very faint. The beta-gal DNA was detected in bombarded hearts but not other organs. CONCLUSIONS: Gene gun-mediated transfer of the episomal vector into beating heart may provide a simple, efficient, and useful strategy for gene therapy.
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MOTIVATION: Structural alignments of superfamily members often exhibit insertions and deletions of secondary structure elements (SSEs), yet conserved subsets of SSEs appear to be important for maintaining the fold and facilitating common functionalities. RESULTS: A database of aligned SSEs was constructed from the structure-based alignments of protein superfamily members in the CAMPASS database. SSEs were classified into several types on the basis of their length and solvent accessibility and counts were made for the replacements of SSEs in different types at structurally aligned positions. The results, summarized as log-odds substitution matrices, can be used for two types of comparisons: (1) structure against structure, both with secondary structure assignments; and (2) structure against sequence with predicted secondary structures. The conservation of SSEs at each alignment position was defined as the deviation of observed SSE frequencies from the uniform distribution. This offers a useful resource to define and examine the core of superfamily folds. Even when the structure of only a single member of a superfamily is known, the extended method can be used to predict the conservation of SSEs. Such information will be useful when modelling the structure of other members of a superfamily or identifying structurally and functionally important positions in the fold.
A malignant pheochromocytoma is described in a 71-year-old man. Osseous metastases became manifest 12 years after successful removal of the primary tumor which originated in paraganglionic tissue near the right adrenal gland. Although the patient had no symptoms of catecholamine excess initially, hypertension, tachycardia and excessive sweating appeared several months before his death, concomitantly with a sharp increase in noradrenaline secretion due to an accelerated growth of metastatic tumors. Since there is no histologic criterion of malignancy in this neoplasm, it would be prudent to consider every case of pheochromocytoma as potentially malignant and to follow-up carefully for a long time after removal of the primary tumor.
BACKGROUND: : Many different methods have been used to assay amylase activity, using nitrophenylated oligosaccharides as substrate; however, the hydrolysis steps in these methods are complex. METHODS: : We developed a new continuously monitoring assay for amylase activity in biological fluids, using 2-chloro-4-nitrophenyl-4-O-beta-D-galactopyranosylmaltoside (GalG2CNP) as the substrate; this assay was used with anti-human salivary amylase monoclonal antibodies for specific determination of the pancreatic isoenzyme. Amylase converted GalG2CNP into beta-D-galactopyranosylmaltose and 2-chloro-4-nitrophenol, which was measured at 405 nm. RESULTS: : GalG2CNP was cleaved between 2-chloro-4-nitrophenol and beta-D-galactopyranosylmaltose and did not undergo transfer reactions. The within-assay CVs (n = 20) for total amylase (T-AMY) and pancreatic amylase (P-AMY) were 0.6-1.6% and 0.5-2.5%, respectively; and day-to-day CVs (n = 10) for T-AMY and P-AMY were 0.8-3.7% and 0.6-4.1%, respectively. T-AMY and P-AMY activities in serum or urine obtained by the proposed method correlated well with those determined by the 2-chloro-4-nitrophenyl 4-O-beta-D-galactopyranosyl-beta-maltotetraoside method or the modified IFCC method. CONCLUSIONS: : This novel assay for T-AMY and P-AMY measures both activities stoichiometrically, directly, and easily, and may be suitable for routine procedures.
It has been postulated that differential pathological diagnosis of lung tumorlet from pulmonary carcinoid is very important to decide the therapeutic strategy, because both of them are pathologically consisted of similar type of cells originated from same cells. At the present, although lung tumorlet is considered to be a hyperplastic lesion of Kultschitzky cells which is located in the epithelial cell of the bronchial mucosa by stimuli such as hypoxia and inflammation, but it occasionally recognized in the normal lung and the concept that it is a subtype of carcnoid is also undeniable. In this paper, a case of lung tumorlet with minute pulmonary carcinoid suggesting a subtype of carcinoid operated upon in our department is presented. Although simple pulmonary resection is a method of choice for pulmonary carcinoid, but it is still controversial as to therapeutic strategy for the lung tumorlet, because it is a benign entity and not tumorous lesion. However pulmonary resection with a close subsequent followed-up study must be a best method of choice for the case with lung tumorlet includes a minute lesion of carcinoid seen in this particular case.
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BACKGROUND: Six-stranded beta barrels with a pseudo-twofold axis are found in several proteins. One group comprises a Greek-key structure with all strands antiparallel; an example is the N-terminal domain of ferredoxin reductase. Others involve parallel strands forming two psi structures (the double-psi beta barrel). A recently discovered example of the latter class is aspartate-alpha-decarboxylase (ADC) from Escherichia coli, a pyruvoyl-dependent tetrameric enzyme involved in the synthesis of pantothenate. RESULTS: Visual inspection and automated database searches identified the six-stranded double-psi beta barrel in ADC, Rhodobacter sphaeroides dimethylsulfoxide (DMSO) reductase, E. coli formate dehydrogenase H (FDHH), the plant defense protein barwin, Humicola insolens endoglucanase V (EGV) and, with a circular permutation, in the aspartic proteinases. Structure-based sequence alignments revealed several interactions including hydrophobic contacts or sidechain-mainchain hydrogen bonds that position the middle beta strand under a psi loop, which may significantly contribute to stabilizing the fold. The identification of key interactions allowed the filtering of weak sequence similarities to some of these proteins, which had been detected by sequence database searches. This led to the prediction of the double-psi beta-barrel domain in several families of proteins in eukaryotes and archaea. CONCLUSIONS: The structure comparison and clustering study of double-psi beta barrels suggests that there could be a common homodimeric ancestor to ADC, FDHH and DMSO reductase, and also to barwin and EGV. There are other protein families with unknown structure that are likely to adopt the same fold. In the known structures, the protein active sites cluster around the psi loop, indicating that its rigidity, protrusion and free mainchain functional groups may be well suited to providing a framework for catalysis.
Correct alignment of the sequence of a target protein with those of homologues of known three-dimensional structure is a key step in comparative modeling. Usually an iterative approach that takes account of the local and overall structural features is required. We describe such an approach that exploits databases of structural alignments of homologous proteins (HOMSTRAD, http:/(/)www-cryst.bioc.cam.ac.uk/ approximately homstrad) and protein superfamilies (CAMPASS, http:/(/)www-cryst.bioc.cam.ac.uk/ approximately campass), in which structure-based alignments are analyzed and formatted with the program JOY (http:/(/)www-cryst.bioc.cam.ac.uk/ approximately joy) to reveal conserved local structural features. The databases facilitate the recognition of a family or superfamily, they assist in the selection of useful parent structures, they are helpful in alignment of the target sequences with the parent set, and are useful for deriving relationships that can be used in validating models. In the iterative approach, a model is constructed on the basis of the proposed sequence alignment and this is then reexpressed in the JOY format and realigned with the parent set. This is repeated until the model and sequence alignment is optimized. We examine the case for comparison and use of multiple structures of family members, rather than a single parent structure. We use the targets attempted by our group in CASP3 to assess the value of such procedures.
OBJECTIVES: We have investigated the effects and outcome from grafting the right internal thoracic artery to the left anterior descending artery in coronary artery bypass grafting. METHODS: We analyzed the findings in 185 patients who underwent coronary artery bypass grafting involving right internal thoracic artery-left anterior descending artery bypass. The survival rate, cardiac events related to the right internal thoracic artery-left anterior descending artery graft, and graft patency were investigated. In cardiac catheterization, the production of nitric oxide from the endothelium of the internal thoracic artery was measured as the plasma nitrite and nitrate levels by the Griess reaction. The reactions to acetylcholine infusion (5 micrograms) in the right internal thoracic artery (n = 4) were compared to those in the left internal thoracic artery (n = 9) grafts. RESULTS: The hospital mortality rate was 0.5%. The actuarial survival rate at 11 years after operation was 98.81%. The rate of freedom from cardiac events at 11 years after operation was 92.08%. The rate of patency of the right internal thoracic artery-left anterior descending artery was 97.0% in 133 patients. Nitric oxide production was calculated as (total nitrite plus nitrate production in response to stimulation by acetylcholine-total nitrite plus nitrate level before acetylcholine load)/(total nitrite plus nitrate level before acetylcholine load). There was no significant difference in changes in plasma concentration in response to acetylcholine stimulation between the right internal thoracic artery-left anterior descending artery and left internal thoracic artery-left anterior descending artery groups (20 +/- 29% versus 5 +/- 10%). CONCLUSIONS: The right internal thoracic artery-left anterior descending artery grafts exhibited good patency and release of nitric oxide in response to acetylcholine loading, similar to left internal thoracic artery-left anterior descending artery grafts.
Pancreatic anomalies are occasionally reported, but complete agenesis of the dorsal pancreas is extremely rare. We report a 47-year-old woman with complete agenesis of the dorsal pancreas. This patient initially presented with jaundice. Computed tomography did not reveal the pancreatic corpus or tail. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography did not visualize the dorsal pancreatic duct. Choledochojejunostomy was performed because she had obstructive jaundice. At laparotomy, there was an enlarged pancreatic head, but no distal pancreas was seen. Histological examination of the pancreatic biopsy specimen showed scattered islets of Langerhans in diffuse fibrosis, with destruction of the glandular parenchyma. This case was diagnosed as complete agenesis of the dorsal pancreas.
Sequences of the insulin receptor (IR), the type-I insulin-like growth-factor receptor (IGFR) and the insulin-receptor-related receptor show that they belong to a homologous family but, until recently, have given few clues about their structures. Three repeats of fibronectin type III have been identified close to the membrane. Although the N-terminal L1, Cys-rich and L2 domains of the IGFR have been identified from their sequences and their structures determined by X-ray crystallography, little is known of their relative positions in the complete receptor in vivo. Here, we ask what can be learnt further from the analysis of sequences, about the structure, organization and function of the extracellular regions of the IR family.
We report 2 cases of rare inflammatory disease of the bladder arising from the bladder submucosa: eosinophilic cystitis in a 33-year-old woman and inflammatory pseudotumor of the bladder in a 41-year-old man. 3D-CT cystography demonstrated submucosal tumorous lesions clearly and enabled the evaluation of mucosae of lesions especially showed the bridging fold-like appearance of the submucosal tumorous lesion in eosinophilic cystitis.