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Biomedical subjects

J Oda

Publications and source records attributed to J Oda.

At least 19 recordsLinked to original sources

Delayed hemispheric neuronal loss in severely head-injured patients.

Recent experimental studies have revealed that traumatic brain injury as well as ischemic brain injury can cause chronic progressive neuronal damage. In the present study, we demonstrate previously unreported delayed cerebral atrophy on computerized tomography (CT) scans in severely head-injured patients. Seventeen severely head-injured patients who required mild hypothermia to control intracranial hypertension after the failure of conventional therapies were retrospectively analyzed. All 17 patients survived more than 1 year. Delayed neuronal loss (DNL) was observed in only eight of the 17 patients. Eight patients with DNL required longer durations of mild hypothermia to control intracranial hypertension than nine patients without DNL. Six of these eight patients with DNL achieved functional recovery despite progressive atrophic changes demonstrated on CT scans. On CT scans, DNL was characterized by (1) the sudden appearance at several months postinjury of a low-density area in the hemisphere ipsilateral to the injury; (2) the preservation of essential cortical structure although related white matter structures showed severe atrophic changes; and (3) no spread of the low-density area to the contiguous territory of the other main cerebral artery. It is concluded that focal primary injury to underlying brain, if severe enough, can result in delayed hemispheric atrophy.

Adolescent↗

Tracer accumulation in radiation necrosis of the brain after thallium-201 SPECT and [11C]methionine PET--case report.

A 69-year-old woman was treated by local irradiation for a malignant lymphoma of the left parotid gland. Three years after the radiation therapy, magnetic resonance imaging revealed heterogeneously enhanced masses in the left temporal lobe and left cerebellum. Thallium-201 chloride single photon emission computed tomography (Tl-SPECT) revealed high uptake and [11C]methionine positron emission tomography (Met-PET) revealed moderate uptake in both masses. Stereotactic biopsy was performed. The histological diagnosis was radiation necrosis. She was treated with steroids. Neurosurgeons should be aware of the difficulty in differentiating tumor recurrence from radiation necrosis even with Tl-SPECT and Met-PET, and the importance of obtaining a histological diagnosis for radiation necrosis.

Aged↗

Fast MR imaging and ultrafast MR imaging of fetal central nervous system abnormalities.

The aims of this study were two: (1) to compare the efficacy of fast MRI (breath-hold fast spin-echo T2-weighted and fast gradient-echo T1-weighted sequence) and ultrafast MRI (half-Fourier acquisition single-shot turbo spin-echo sequence) in evaluation of fetal central nervous system (CNS) abnormalities at late gestational age, and (2) to compare the capability of fast MRI and ultrafast MRI to assess fetal CNS abnormalities with that of prenatal ultrasonography (US). Forty-nine women with fetuses at gestational ages of 26-39 weeks underwent fast MRI (29 patients) or ultrafast MRI (20 patients). In detection of motion artifact, visualization of the lateral and 4th ventricles, and differentiation between gray and white matter in cerebral hemispheres, ultrafast MRI was significantly superior to fast MRI (p< 0.0001, Mann-Whitney U test). In 25 of 43 cases, US and MR diagnoses were the same and consistent with postnatal diagnosis. In 10 of 43 cases, MRI demonstrated findings additional to or different from those of US, and MR findings were confirmed postnatally. MRI, particularly ultrafast MRI, is useful for demonstrating CNS abnormalities in situations in which US is suggestive but not definitive.

Anencephaly↗

Concomitant laparoscopic hand-assisted radical nephrectomy and open radical prostatectomy using a single lower midline incision.

The hand-assist technique offers the urologic surgeon several advantages. The technique provides the novice laparoscopist a logical segue into minimally invasive surgery by literally allowing one hand to remain in the realm of open surgery. Hand-assist access affords the laparoscopist the use of tactile sensation and blunt manual dissection and retraction. We describe an additional benefit of the hand-assist technique. In clinical situations in which more than one procedure is required, a properly positioned hand-assist device will avoid the need for two large incisions. We present simultaneous hand-assisted laparoscopic radical nephrectomy and open radical prostatectomy performed through a single midline incision.

Abdominal Muscles↗

The impact of a catastrophic earthquake on morbidity rates for various illnesses.

It has been reported that some natural catastrophes increase morbidity rates for illness. In this study, we investigated the impact of the 1995 Hanshin-Awaji earthquake on morbidity rates for various illnesses by analysis for correlations between the extent of damage due to the earthquake and occurrences of various illnesses. We searched the medical records of 1948 patients hospitalized due to illness in 48 hospitals during the first 15 days after the earthquake. In each of 14 affected areas, the hospital admission rate and estimated morbidity ratio for each illness were calculated. Destruction ratios were determined based upon the number of dwellings completely destroyed in each area. For total illnesses and each major illness, linear regression analyses were performed comparing hospital admission rates, estimated morbidity ratios, and destruction ratios. Hospital admission rates and estimated morbidity ratios among the 1948 patients were significantly correlated to destruction ratios. With pneumonia, dehydration, acute heart failure, asthmatic attack, and peptic ulcer, hospital admission rates and estimated morbidity ratios were significantly related to destruction ratios, while no significant correlations between estimated morbidity ratios and destruction ratios existed for cerebral vascular disease or ischemic heart disease. Peptic ulcer and pneumonia showed especially high correlation values (age- and sex-adjusted R2>0.7). The present study revealed a strong link between the extent of damage due to the catastrophic earthquake and an increase in morbidity rates for acute illnesses, especially peptic ulcer and pneumonia.

Adolescent↗

Interleukin-1beta alters the oxygen delivery-oxygen consumption relationship in rabbits by increasing the slope of the supply-independent line.

When systemic oxygen delivery (DO2) is reduced, oxygen consumption (VO2) is maintained until a critical level is reached (DO2crit). Sepsis is thought to shift DO2crit to the right and lengthen the supply-dependent portion. We tested the effect of interleukin (IL)-1beta, which is one of the key cytokines related to sepsis, on the DO2-VO2 relationship. Fifteen rabbits were subjected to stepwise cardiac tamponade to reduce DO2 to 10% by inflating a handmade balloon placed into the pericardial sac. Seven rabbits were given 10 microg/kg of IL-1beta intravenously (IL-1beta group) prior to the graded cardiac tamponade. The remainder received saline alone (control group). The DO2-VO2 relationship was analyzed by the dual-line method. IL-1beta significantly decreased mean arterial pressure (65 +/- 11 mmHg from baseline 85 +/- 7 mmHg) without altering cardiac output. The IL-1beta group showed significantly steeper supply-independent line slopes than did the control group (0.19 +/- 0.02 vs. 0.11 +/- 0.02, respectively), which resulted in a DO2crit shift to the left (IL-1beta group, 8.7 +/- 1.7 ml/kg x min vs. control, 11.7 +/- 0.7 ml/kg x min). The IL-1beta group also showed greater PO2 and plasma lactate levels in the portal vein than did the control group. These results indicate that IL-1beta impairs systemic oxygen uptake even before VO2 becomes supply-dependent, presumably due to maldistribution of the blood flow including the splanchnic circulation.

Animals↗

Catalytic activity of anion-exchange resins modified with metal-porphine in oxidative reactions of phenols.

Anion-exchange resins modified with metal-porphine (M-Pr) have been investigated to develop a solid catalyst in the oxidative reaction of phenols by O2 in air. Co-Pr, which is easily prepared and separable from the reaction mixture, has been proved to accelerate the oxidative reaction of phenols such as 3,5-di-tertbutyl-4-hydroxyanisole. The resulting main oxidative products were identified to be quinones by using the GC-MS method.

Anion Exchange Resins↗

Structure of tropinone reductase-II complexed with NADP+ and pseudotropine at 1.9 A resolution: implication for stereospecific substrate binding and catalysis.

Tropinone reductase-II (TR-II) catalyzes the NADPH-dependent reduction of the carbonyl group of tropinone to a beta-hydroxyl group. The crystal structure of TR-II complexed with NADP+ and pseudotropine (psi-tropine) has been determined at 1.9 A resolution. A seven-residue peptide near the active site, disordered in the unliganded structure, is fixed in the ternary complex by participation of the cofactor and substrate binding. The psi-tropine molecule is bound in an orientation which satisfies the product configuration and the stereochemical arrangement toward the cofactor. The substrate binding site displays a complementarity to the bound substrate (psi-tropine) in its correct orientation. In addition, electrostatic interactions between the substrate and Glu156 seem to specify the binding position and orientation of the substrate. A comparison between the active sites in TR-II and TR-I shows that they provide different van der Waals surfaces and electrostatic features. These differences likely contribute to the correct binding mode of the substrates, which are in opposite orientations in TR-II and TR-I, and to different reaction stereospecificities. The active site structure in the TR-II ternary complex also suggests that the arrangement of the substrate, cofactor, and catalytic residues is stereoelectronically favorable for the reaction.

Alcohol Oxidoreductases↗

Site-directed mutagenesis of putative substrate-binding residues reveals a mechanism controlling the different stereospecificities of two tropinone reductases.

Two tropinone reductases (TRs) constitute a key branch point in the biosynthetic pathway of tropane alkaloids, which are mainly produced in several solanaceous plants. The two TRs share 64% identical amino acid residues and reduce the 3-carbonyl group of a common substrate, tropinone, but they produce distinct alcohol products with different stereospecific configurations. Previous x-ray crystallographic analysis has revealed their highly conserved overall folding, and the modeling of tropinone within the putative substrate-binding sites has suggested that the different stereospecificities may be determined solely by the different binding orientations of tropinone to the enzymes. In this study, we have constructed various mutant TRs, in which putative substrate-binding residues from one TR were substituted with those found in the corresponding positions of the other TR. Substitution of five amino acid residues resulted in an almost complete reversal of stereospecificity, indicating that the different stereospecificities are indeed determined by the binding orientation of tropinone. Detailed kinetic analysis of the mutant enzymes has shown that TR stereospecificity is determined by varying the contributions from electrostatic and hydrophobic interactions and that the present TR structures represent highly evolved forms, in which strict stereospecificities and rapid turnover are accomplished together.

Alcohol Oxidoreductases↗

Crystal structure of tobacco PR-5d protein at 1.8 A resolution reveals a conserved acidic cleft structure in antifungal thaumatin-like proteins.

The crystal structure of tobacco PR-5d, an antifungal thaumatin-like protein isolated from cultured tobacco cells, was determined at the resolution of 1.8 A. The structure consists of 208 amino acid residues and 89 water molecules with a crystallographic R-factor of 0.169. The model has good stereochemistry, with respective root-mean-square deviations from the ideal values for bond and angle distances of 0.007 A and 1.542 degrees. Of the homologous PR-5 proteins, only those with antifungal activity had a common motif, a negatively charged surface cleft. This cleft is at the boundary between domains I and II, with a bottom part consisting of a three-stranded antiparallel beta-sheet in domain I. The acidic residues located in the hollow of the cleft form the beta-sheet region. Sequence and secondary structure analyses showed that the amino acid residues comprising the acidic cleft of PR-5d are conserved among other antifungal PR-5 proteins. This is the first report on the high-resolution crystal structure of an antifungal PR-5 protein. This structure provides insight into the function of pathogenesis-related proteins.

Amino Acid Sequence↗

Morbidity and mortality of hospitalized patients after the 1995 Hanshin-Awaji earthquake.

The objective of this study was to provide an overview of the morbidity and mortality of hospitalized patients during the Hanshin-Awaji earthquake. Medical records of 6,107 patients admitted to 95 hospitals (48 affected hospitals within the disaster area and 47 back-up hospitals in the surrounding area) during the initial 15 days after the earthquake were analyzed retrospectively. Patient census data, diagnoses, dispositions, and prognoses were considered. A total of 2,718 patients with earthquake-related injuries were admitted to the 95 hospitals included in our survey, including 372 patients with crush syndrome and 2,346 with other injuries. There were 3,389 patients admitted with illnesses. Seventy-five percent of the injured were hospitalized during the first 3 days. In contrast, the number of patients with illnesses continued to increase over the entire 15-day period after the earthquake. The mortality rates were 13.4% (50/372), 5.5% (128/2,346), and 10.3% (349/3,389) associated with crush syndrome, other injuries, and illness, respectively. The overall mortality rate was 8.6% (527/6,107 patients). Morbidity as well as mortality rates increased with age in patients with both injuries and illnesses. In the initial 15-day period, there was an unprecedented number of patients suffering from trauma, and they converged upon the affected hospitals. Subsequently an increased incidence of illness was observed. This survey underscores the need for adequate disaster response in such an urban situation.

Adolescent↗

Changes in left ventricular performance in patients with severe head injury during and after mild hypothermia.

OBJECTIVE: To evaluate left ventricular (LV) performance in patients with severe head injury during and after mild hypothermia. PATIENTS AND METHODS: Seven consecutive patients who underwent therapeutic mild hypothermia (age, 15 to 70 years; Glasgow Coma Scale score on admission, 4 to 8). LV performance was assessed by using M-mode, color tissue Doppler imaging tracings and pulsed Doppler echocardiography. LV contraction and relaxation were evaluated by using the peak velocity of LV posterior wall movement during systole (Smax) and diastole (Dmax), respectively, in addition to the conventional echocardiographic indices. RESULTS: Mild hypothermia increased LV ejection time and reciprocally reduced LV filling period as indicated by temperature-dependent shortening of the early diastolic filling and the total diastolic inflow time. The indices depending on temporal factors such as ejection time, Smax, or Dmax were significantly affected by mild hypothermia, whereas those depending on spatial factors such as fractional shortening or stroke volume index were not. The attenuated Smax was compensated for the prolonged ejection time resulting in the relatively consistent fractional shortening regardless of body temperature. There was no compensatory mechanism for the decreased Dmax during diastole. CONCLUSION: The effect of mild hypothermia seemed to be predominantly negatively chronotropic. LV diastolic function was more vulnerable to mild hypothermia than LV systolic function was.

Adolescent↗

[A case of hepatocellular carcinoma with tumor thrombus in the right atrium successfully treated by arterial administration of lipiodol-SMANCS].

In February, 1996, a 73-year-old male with liver dysfunction was admitted to our hospital for further examination and treatment of liver tumor. The liver tumor was revealed by imaging examination, which was mainly in the S4-S8 of liver with a thrombus growing from the right anterior branch to the right branch of the portal vein, and from the right hepatic vein to the inferior vena cava and right atrium. The serum AFP and PIVKA-II levels were elevated to 3.610 ng/ml and 54 AU/ml, respectively. The patient was diagnosed as having hepatocellular carcinoma, and was treated by arterial administration of anticancer drugs (epirubicin hydrochloride, mitomycin C and carboplatin) and TAE. Though the main tumor (S4-S8 of liver) was reduced by TAE, the portal and atrial tumor thrombus did not respond. One month after TAE (20 May, 1996), the first arterial administration of Lipiodol-SMANCS was given, followed by 4 successive procedures with an interval of about 1.5 months (total dose 15 mg), resulting in remarkable tumor thrombus shrinkage and reduction of AFP levels to 80 ng/ml. This case shows that arterial administration of SMANCS may be one of the effective treatments for hepatocellular carcinoma, even with tumor thrombus of hepatic vein, IVC and right atrium.

Aged↗

Crystallization and preliminary crystallographic study of tropinone reductase II from Datura stramonium.

Tropinone reductase II is an NADPH-dependent oxidoreductase involved in a plant alkaloid metabolism. The enzyme from Datura stramonium has been crystallized using 2-methyl-2,4-pentanediol as a precipitant and a macro-seeding technique. The crystal belongs to space group P42212, with cell dimensions a = b = 62.8 and c = 128.4 A. A data set to 2.6 A resolution has been collected at a cryogenic temperature.

Alcohol Oxidoreductases↗

Crystal structures of two tropinone reductases: different reaction stereospecificities in the same protein fold.

A pair of tropinone reductases (TRs) share 64% of the same amino acid residues and belong to the short-chain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups with different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-A resolutions. The overall folding of the two enzymes was almost identical. The conservation was not confined within the core domains that are conserved within the protein family but extended outside the core domain where each family member has its characteristic structure. The binding sites for the cofactor and the positions of the active site residues were well conserved between the two TRs. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes. A modeling study indicated that these charged residues play a major role in controlling the binding orientation of tropinone within the substrate binding site, thereby determining the stereospecificity of the reaction product. The results obtained herein raise the possibility that in certain cases different stereospecificities can be acquired in enzymes by changing a few amino acid residues within substrate binding sites.

Alcohol Oxidoreductases↗

Toward the antibody-catalyzed chemiluminescence. Design and synthesis of hapten.

Hapten 4 was synthesized to generate catalytic antibodies triggering chemiluminescence by catalyzing the decomposition of the 1,2-dioxetane 3. The hapten 4 was so designed as to elicit a negatively charged functional group in the antibody combining site to catalyze the beta-elimination of the protecting group in 3 as well as to lock the protecting group into an energetically favorable anti-periplanar conformation.

Antibodies, Catalytic↗

Design, synthesis and evaluation of transition-state analogue inhibitors of Escherichia coli gamma-glutamylcysteine synthetase.

Phosphinic acid-, sulfoximine- and sulfone-based transition-state analogues were synthesized and evaluated as inhibitors of Escherichia coli gamma-glutamylcysteine synthetase. These compounds have a carboxyl function at the beta-carbon to the tetrahedral central hetero atom so as to mimic the carboxyl group of the attacking cysteine in the transition state. The phosphinic acid- and the sulfoximine-based compounds were found to be potent ATP-dependent inactivators, both showing a slow-binding kinetics with overall affinities and second-order inactivation rates of one to two orders of magnitude greater than those of L-buthionine (SR)-sulfoximine (L-BSO). The sulfone was a simple reversible inhibitor without causing ATP-dependent enzyme inactivation, but its affinity toward the enzyme was still five times greater than that of L-BSO, indicating that the beta-carboxyl function plays a key role in the recognition of the inhibitors by the enzyme. The sulfoximine with (S)-beta-carbon to the sulfur was synthesized stereoselectively, and the two diastereomers with respect to the chiral sulfur atom were separated as a cyclic sulfoximine derivative. The sulfoximine with R-configuration around the sulfur served as an extremely powerful ATP-dependent inactivator with an overall inhibition constant of 39 nM and an inactivation rate of 6750 M-1 s-1, which correspond to 1260-fold higher affinity and almost 1400-fold greater inactivation rate as compared with L-BSO. The sulfoximine with (S)-sulfur was a simple reversible inhibitor with an inhibition potency comparable to that of the sulfone. The synthesis and inhibition profile of the N-phosphoryl sulfoximine is also described.

Butyrates↗

Crystal structure of asparagine synthetase reveals a close evolutionary relationship to class II aminoacyl-tRNA synthetase.

The crystal structure of E. coli asparagine synthetase has been determined by X-ray diffraction analysis at 2.5 A resolution. The overall structure of the enzyme is remarkably similar to that of the catalytic domain of yeast aspartyl-tRNA synthetase despite low sequence similarity. These enzymes have a common reaction mechanism that implies the formation of an aminoacyl-adenylate intermediate. The active site architecture and most of the catalytic residues are also conserved in both enzymes. These proteins have probably evolved from a common ancestor even though their sequence similarities are small. The functional and structural similarities of both enzymes suggest that new enzymatic activities would generally follow the recruitment of a protein catalyzing a similar chemical reaction.

Amino Acid Sequence↗