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Biomedical subjects

K Shiga

Publications and source records attributed to K Shiga.

At least 91 records · Page 5Linked to original sources
PubMed1990

Proton release from flavoprotein D-amino acid oxidase on complexation with the zwitterionic ligand, trigonelline.

Trigonelline, i.e., N-methylnicotinate, which has a zwitterionic structure similar to a substrate D-amino acid, is a useful active site probe for D-amino acid oxidase (DAO). The affinity of trigonelline for DAO in the deprotonated state at the enzyme bound FAD 3-imino group is higher than in the neutral state, contrary to in the case of benzoate, which is a competitive inhibitor and is in a monoanionic form. The time course of the absorbance change was monitored for the binding of DAO with trigonelline by means of a stopped-flow technique. The reaction, on monitoring at 507 nm, was found to be biphasic at pH 8.3, with fast and slow phases. The dissociation of the 3-imino proton of the enzyme bound FAD was observed in the same time course as the slow phase. These results suggest that the positive charge of trigonelline exists near the 3-imino group of the enzyme bound FAD and interacts repulsively with the proton of the 3-imino group. The absorption spectra of the DAO-trigonelline complex at various pHs also support this hypothesis. In the catalysis of DAO, a similar mechanism may be involved, that is, the positive charge of a D-amino acid may interact repulsively with the 3-imino proton of the enzyme bound FAD, and this interaction may be important for the catalysis.

Alkaloids↗
PubMed1990

[Regional myocardial blood flow measurements in resting and dipyridamole induced vasodilative state by Xenon-133 clearance method].

Myocardial imaging with Xenon-133 and a gamma camera was employed to evaluate the relationship between angiographically demonstrated coronary artery stenosis and regional myocardial blood flow (r-MBF) in 22 patients with ischemic heart disease and 9 control subjects. After a left anterior oblique cineangiogram was obtained, the cinecamera was replaced by the mobile gamma camera in the same plane and location over the pericardium of patients. Then, 370 MBq (10 mCi) of 133Xe was injected into the left coronary artery as a bolus. After the first measurement of r-MBF in resting state, a second injection was made 3 minutes after intravenous injection of 0.56 mg/kg of dipyridamole for 4 minutes. The r-MBF in different regions of the heart was calculated by Kety formula. Coronary flow reserve (CFR) was defined the rMBF ratio between resting and dipyridamole induced vasodilative state. In the resting state, good correlation (r = 0.711) was observed between pressure rate product and the r-MBF at the areas perfused by non stenotic vessels. The r-MBF of the areas perfused by severe stenotic vessels (greater than 90%) was smaller than that of the areas perfused by non stenotic vessels, however there was overlapping of flow. In the dipyridamole induced vasodilative state, the r-MBF of the areas perfused by intact vessels increased approximately 2.4 times of the resting state, and showed good correlation with pressure rate product. In contrast, the r-MBF of the areas perfused by stenotic vessels did not correlate with pressure rate product, but depended on the degrees of coronary stenosis (50-75% stenosis; 1.9 times, greater than 90% stenosis; 1.3 times, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[Regional myocardial coronary blood flow reserve in hypertrophic cardiomyopathy assessed by digital subtraction coronary angiography].

Previous observations suggest the presence of ischemia in the disproportionately thickened interventricular septum (IVS) of patients with hypertrophic cardiomyopathy (HCM), although the details remain obscure. Utilizing digital subtraction coronary angiography (DSA) with LAO projection before and after intracoronary papaverine (P) injection, we evaluated regional myocardial coronary blood flow reserve (rMFR) consecutively 18 patients with HCM, and compared it with that of 8 patients without apparent cardiac abnormality (C). Time-density curves were obtained from digital angiograms of the myocardial region of interest. We measured peak contrast density (Cm) and time to peak contrast (Tm). An index of rMFR was calculated as the quotient of Cm/Tm before and after P. In HCM, rMFR in IVS and apex was significantly lower than that of C (Mid-IVS: 1.9 +/- 0.5 vs 3.9 +/- 0.5, p less than 0.001; Low-IVS: 2.0 +/- 0.5 vs 4.4 +/- 0.9, p less than 0.001; Apex: 2.0 +/- 0.7 vs 4.5 +/- 1.6, p less than 0.01). There was correlation between the impairment of rMFR and the extent of hypertrophy in HCM. In conclusion, we could state that, in HCM, the region of impaired myocardial coronary blood flow reserve is localized. In HCM, DSA is useful in evaluating myocardial coronary blood flow reserve.

Adult↗
PubMed1990

[Assessment of transient dilation of the left ventricular cavity in patients with hypertrophic cardiomyopathy by exercise thallium-201 scintigraphy].

Exercise Tl scintigraphy (EX-Tl) provides a noninvasive means of identifying myocardial perfusion abnormalities in patients (pts) with hypertrophic cardiomyopathy (HCM). We have noted that some pts with HCM have a pattern of transient dilation of the left ventricle (LV) on the immediate post exercise images as compared with 3 hour redistribution images. We presumed that left ventricular dilation was caused by subendocardial hypoperfusion. So we studied transient dilation of the LV in 50 pts with HCM and 20 controls (C). Initial and delayed conventional short tomographic images were obtained after reconstruction of 30 projections acquired over 180 degrees. Thirty six radii every 10 degrees were generated from the center of the middle myocardial images of the short axis. An area surrounded by the thirty six points of maximal count on each radius was calculated in initial and delayed images. Transient Dilation Index (TDI) as an index of dilation was determined by dividing an area in initial image by an area in delayed image. TDI in pts with HCM was larger than that in C. Pts with HCM were classified into the two groups, Group A: TDI greater than 1.11 (mean + 2 SD in C), 24 pts, Group B: TDI greater than 1.11, 26 pts. Frequency of pts with history of chest pain in Group A was higher than that in Group B, and frequency of pts with positive exercise ECG in Group A was higher than that in Group B. End diastolic volume in Group B did not change 10 minutes after exercise by radionuclide ventriculography. In conclusion, transient dilation of the LV in pts with HCM by EX-Tl is in appearance, and may reflect subendocardial ischemia.

Adult↗
PubMed1990

[Utility of reinjection method in stress Tl-201 myocardial scintigraphy to assess viability of the infarcted myocardium].

To assess viability of the infarcted myocardium, we performed stress Tl-201 myocardial scintigraphy using reinjection method in 37 patients with old myocardial infarction, and in 13 patients of them, Tl myocardial imagings were performed in resting state on the other day within 4 weeks after this examination. In this method, 111 MBq (3 mCi) of thallium was injected at the peak of exercise and initial and delayed images were acquired, then additionally 37 MBq (1 mCi) of thallium was injected after delayed scanning (reinjection) and we obtained post-reinjection images. Delayed images showed redistribution in 15 patients (41%), and no redistribution in 22 patients (59%). In post-reinjection images, 7 (19%) of 15 patients with redistribution and 3 (8%) of 22 patients without redistribution showed improvement of thallium uptake, in total 10 patients (27%) had additional thallium uptake in infarcted regions. And the degree of thallium uptake in post-reinjection images were almost equal to that in resting images. In conclusion, myocardial imaging using thallium reinjection method may be useful for the assessment of viability of the infarcted myocardium.

Female↗
PubMed1989

Effects of pH and ionic strength on the binding of egg white riboflavin binding protein with flavins.

The effects of pH and ionic strength on the equilibrium constants and rate constants (binding and dissociation rate constants) between riboflavin binding protein (RBP) and flavins (riboflavin, 3-carboxymethylriboflavin [CMRF], and FMN) were studied by fluorometry. The equilibrium constant and the binding rate constant between RBP and riboflavin were pH-independent between pH 6 and 9, and both constants were also independent of the ionic strength, while the constants between RBP and CMRF or FMN were dependent on both pH and ionic strength. The dissociation rate constants between RBP and the flavins used here were not so dependent on pH and ionic strength in the pH region 6 to 9, and the patterns of pH profiles as a whole were similar to each other, although the constants for FMN were about 30-60 times larger than those for CMRF or riboflavin. RBP had lower affinity for FMN than for riboflavin in the neutral pH region, which is based on the small binding rate constant and the large dissociation rate constant for FMN. The former is due to an electrostatic repulsion force between negative net charges of RBP and the phosphate group of FMN, and the latter is due to steric interference by the phosphate group of FMN.

Animals↗
PubMed1989

[An examination of left ventricular peak filling rate and ventricular relaxation rate by simultaneous acquisition of radionuclide ventriculography and left ventricular pressure].

We investigated whether peak filling rate (PFR) obtained from ECG gated radionuclide ventriculography (RNV) reflects left ventricular (LV) relaxation rate or not. Five patients with angina pectoris, 5 patients with old myocardial infarction and 6 controls were studied by simultaneous acquisition of RNV and LV pressure. RNV was performed in modified left anterior oblique position before and during angiotensin II (A II) infusion to elevate their blood pressure about 25 mmHg (A-1) and 50 mmHg (A-2). The data were acquired in a list mode and LV volume curves were reconstructed by forward and backward gating from the R wave of ECG. Actual PFR and corrected PFR by stroke volume (/SV), by end diastolic volume (/EDV), by instantaneous volume (/IV) were calculated from LV volume curve and its first differential curve. LV pressure was simultaneously measured by the catheter-tip micromanometer, and the time constant (T) of assumed exponential decline in LV pressure was calculated as index of LV relaxation rate. Although there was no correlation between actual PFR and T, corrected PFR (/EDV) and PFR (/IV) correlated with T. PFR (/EDV) decreased and T increased during A-1 and A-2. Decrease of PFR (/EDV) corresponded with increase of T. Thus, corrected PFR (/EDV) obtained from RNV reflects the rate of LV relaxation, and was considered to be an useful index to evaluate LV diastolic function.

Adult↗
PubMed1989

[An attempt of thallium-201 myocardial perfusion imaging during transient coronary arterial occlusion by PTCA].

To evaluate the myocardial perfusion during transient coronary occlusion, we attempted to obtain the myocardial scintigraphy during percutaneous transluminal coronary angioplasty (PTCA). Tl-201 was injected at the last inflation of angioplastic balloon and occlusion was kept on for 60 sec. Planar images or SPECT were obtained immediately after PTCA. With this protocol, myocardial perfusion defects were observed during PTCA and fully redistributed 3 hours after Tl injection. Extent of ischemic lesions were almost same as that observed during exercise in two cases without collateral vessels. In a case with well visualized collateral vessels, perfusion defect was smaller in PTCA images than that in exercise stressed images. We conclude that intravenous injection of Tl-201 during PTCA is useful to assess the alteration of myocardial perfusion due to transient coronary occlusion without increasing the risk of angioplastic procedure.

Adult↗
PubMed1989

[Evaluation of transient dilation of the left ventricle on exercise thallium-201 scintigraphy].

We have noted that some patients with ischemic heart disease have a pattern of transient dilation of the left ventricle on the immediate post exercise images as compared with 3 hour redistribution images. We assessed correlation between transient dilation of the left ventricle and coronary arteriographic findings in 32 patients with ischemic heart disease and 15 controls. Initial and delayed conventional short axis tomographic images were obtained after reconstruction of 20 projections acquired over 180 degrees. Thirty six radii by every 10 degrees were generated from the center of the middle myocardial images of the short axis. An area surrounded by thirty six points of maximal count on each radius was calculated in initial and delayed images. Transient Dilation Index (TDI) as an index of dilation was determined by dividing an area in initial image by an area in delayed image. There was no difference in TDI between patients with 1 vessel disease and controls, but TDI in patients with two vessel disease and patients with three vessel disease was larger than that in controls. Thus, transient dilation of the left ventricle on exercise Tl scintigraphy was likely to be related to number of stenotic vessel. We concluded that TDI as a simple quantitative index of transient dilation of the left ventricle was useful for detecting multi vessel stenosis.

Cardiomyopathy, Dilated↗
PubMed1989

Two cases of pancreatic cystadenocarcinoma with elevated CA 19-9 levels in the cystic fluid in comparison with two cases of pancreatic cystadenoma.

A 39-year-old woman was hospitalized with left hypochondralgia. Ultrasonography and abdominal computed tomography showed a cystic mass in the tail of the pancreas. Echo-guided aspiration of the cyst was performed, and a markedly elevated CA 19-9 level in the cystic fluid was found. A surgical operation was performed, and the tumor was radically resected. The pathologic diagnosis was papillary adenocarcinoma of the pancreas. Another case of pancreatic cystadenocarcinoma also had an extremely high cystic CA 19-9 level, whereas two cases with benign pancreatic cysts had very low cystic CA 19-9 levels. Moreover, positive localization of CA 19-9 in the cancerous tissue was clearly demonstrated by an immunohistochemical technique, indicating active secretion of CA 19-9 into the cyst, while CA 19-9 in the tissue of pancreatic cystadenoma was almost non-existent. Measurement of the CA 19-9 level in the cystic fluid might therefore be a valuable additional aid in the diagnosis of cystadenocarcinoma of the pancreas.

Adult↗
PubMed1988

A novel gene activated in regenerating islets.

Administration of poly(ADP-ribose) synthetase inhibitors such as nicotinamide to 90% depancreatized rats induces regeneration of pancreatic islets, thereby ameliorating the surgical diabetes (Yonemura, Y., Takashima, T., Miwa, K., Miyazaki, I., Yamamoto, H., and Okamoto, H. (1984) Diabetes 33, 401-404). In screening the regenerating islet-derived cDNA library, we came across a novel gene encoding a 165-amino acid protein. The gene was expressed in regenerating islets but not in normal pancreatic islets, insulinomas, or regenerating liver. In 90% depancreatized and nicotinamide-injected rats, the expression of the gene was increased 1 month after the partial pancreatectomy and reached a peak 3 months after the operation. The increase in expression of the gene was temporally correlated with the increase in size of regenerating islets and the decrease in urinary glucose level. The gene was also found to be activated in hyperplastic islets of aurothioglucose-treated mice. Thus, the expression of the gene in both regenerating and hyperplastic islets suggests possible roles for this gene in replication, growth, and maturation of islet beta-cells. We also found that a human pancreas-derived cDNA library contained a homologue to the gene.

Amino Acid Sequence↗
PubMed1988

Resonance Raman spectra of anionic semiquinoid form of a flavoenzyme, D-amino acid oxidase.

Resonance Raman (RR) spectra of the complex of anionic semiquinoid D-amino acid oxidase (DAO) with picolinate in H2O and D2O were observed in the 300-1,750 cm-1 region. RR spectra were also measured for the complex of the semiquinoid enzyme reconstituted with isotopically labeled FAD's, i.e., [4a-13C]-, [4,10a-13C2]-, [2-13C]-, [5-15N]-, and [1,3-15N2]-FAD. On the basis of the isotope effects, tentative assignments of the observed bands of the anionic semiquinoid flavin were made. The spectra differ from those of oxidized, neutral semiquinoid, and anionic reduced flavins previously reported. The 1,602 cm-1 band was not shifted for any FAD labeled in ring II and/or ring III and was assigned to a ring I mode. The 1,516 cm-1 band underwent an isotopic shift upon [4a-13C]- or [4,10a-13C2]-labeling. The band was assigned to the mode containing C(4a)-C(10a) stretching. The 1,331 and 1,292 cm-1 bands shifted upon [4a-13C]- or [5-15N]-labeling and were assigned to the modes containing C(4a)-N(5) stretching. The 1,217 and 1,188 cm-1 bands were assigned to the skeletal vibrations of ring III coupled with the N(3)-H bending mode. The RR spectrum of the complex of anionic semiquinoid DAO with alpha-iminopropionate or N-methyl-alpha-iminopropionate was essentially identical with that of the complex with picolinate.

Animals↗
PubMed1988

Complex formation between anionic semiquinoid form of a flavoenzyme D-amino acid oxidase and ligands. Stabilizing mechanism of anionic semiquinoid flavoenzyme.

Picolinate binds to the anionic semiquinoid form of D-amino acid oxidase (DAO), and the complex formed has a broad absorption band in the long-wavelength region extending beyond 800 nm, which is reminiscent of a charge transfer interaction. The binding has a stoichiometry of 1:1 with respect to the enzyme. The dissociation constant at 25 degrees C was 30 microM at pH 7.0. The pH dependence (pH 7.0-8.3) of the dissociation constant indicates that one proton is associated with the complex formation, and suggests that picolinate able to bind to the anionic semiquinoid enzyme is in the cationic form protonated at the nitrogen atom. By adding dithionite to the oxidized DAO solution containing pyruvate and various amines, a similar anionic semiquinoid DAO complex having a broad long-wavelength absorption band, appeared. Resonance Raman spectra with excitation at 623.8 nm of the anionic semiquinoid DAO complex formed in the presence of pyruvate and methylamine indicate that the complex consists of the anionic semiquinoid DAO and N-methyl-alpha-iminopropionate produced from pyruvate and methylamine, and that the imino group must be protonated. This supports the proposal that the presence of a positively charged group in the vicinity of flavin is required for the stabilization of the anionic semiquinoid flavin. The results also suggest that the broad absorption band is derived from the charge transfer interaction between the anionic semiquinoid flavin and the imino acid, in which the flavin C(4a)-N(5) locus and the locus containing (Formula: see text) of the amino acid are important for the interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗
PubMed1988

[Improvement of treatment of carcinoma of the thoracic esophagus, especially in reference to the transition in postoperative combined therapy].

It has become clear that postoperative combined therapy performed in our department has improved the prognosis of patients with carcinoma of the thoracic esophagus and changed the pattern of recurrence. In cases of postoperative radioimmunochemotherapy (a combination of 4000 rad of irradiation, with administration of 5-Fu and bleomycin, and the prescription of OK-432 and/or PSK after irradiation) was effective in preventing recurrence. In cases of n1(+) and n2(+), such therapy was effective in controlling local recurrence such as cervical and thoracic nodes. However, the 5-year survival rate of this group was 44.3%, indicating a need for more effective postoperative therapy. Thus, new radiochemoimmunotherapy (irradiation 4000R, 15-30mg/m2 x 2 CDDP, 2mg/body x 2 VDS) combined with three kinds of cytokines such as tumor necrosis factor (TNF), interleukin-II (IL-II) and interferon (IFN)-alpha has been applied in cases of n1(+), n2(+). Postoperative aggressive chemotherapies (old protocol, PAM treatment with a combination of Pepleomycin, Adriamycin and Mitomycin: Or new protocol, F.CAV treatment with a combination of 5-Fu, CDDP, Adriamycin and Vindesine) were effective in improving the prognosis of patients with n3(+) and n4(+). The 5-year survival rate improved from 2.7% with other therapies to 20. 5% with this therapy.

Combined Modality Therapy↗
PubMed1987

Evolutionary conservation of the insulinoma gene rig and its possible function.

We have identified a gene, rig (rat insulinoma gene), that is activated in chemically induced rat insulinomas but not in normal pancreatic islets or in regenerating islets. In the present study, we have found that the insulinoma gene was activated in a BK virus-induced hamster insulinoma cell line and in a spontaneously occurring human insulinoma. From the hamster and human insulinoma cDNA libraries, rig homologues were isolated, and their nucleotide sequences were determined. In the same manner as the rat gene, both hamster and human homologues contained one open reading frame of 435 nucleotides, differing by 32- and 41-base substitutions, respectively. All the base substitutions were same-sense mutations. Accordingly, the deduced 145-amino acid sequence remained invariant in hamster, human, and rat insulinomas, suggesting that rig has evolved under extraordinarily strong selective constraints. Computerized structure analysis indicated that rig-encoded protein is a possible DNA-binding protein. The antisense oligodeoxyribonucleotide complementary to hamster rig mRNA was synthesized and injected into the hamster insulinoma cells. The antisense rig oligodeoxyribonucleotide inhibited DNA synthesis in the insulinoma cells, whereas the sense rig oligodeoxyribonucleotide or antisense insulin oligodeoxyribonucleotide had no inhibitory effect. These results strongly suggest that the activation of rig is both common and potentially significant in the oncogenic growth of pancreatic B cells of islets of Langerhans.

Adenoma, Islet Cell↗
PubMed1987

Kinetic and equilibrium studies on the interaction of reduced flavoprotein D-amino acid oxidase with pyridine carboxylates.

The equilibrium constants and the rate constants (binding and dissociation constants) between reduced D-amino acid oxidase and pyridine carboxylates were obtained at various pH values (from pH 6.0 to 8.3). The pH dependence of the constants is consistent with the previous conclusion from a resonance Raman study that pyridine carboxylates in the form of a cation protonated at the N atom can bind to the reduced enzyme, but those in the neutral form cannot bind, showing that the positive charge of cationic pyridine carboxylates interacts with the negative charge of the anionic reduced flavin in the reduced enzyme. The binding rate constants of picolinate and nicotinate in the cationic form for the reduced enzyme were quite similar to each other, but the dissociation rate constant of picolinate is several times smaller than that of nicotinate. Thus, it is concluded that the difference in affinity of picolinate and nicotinate for the reduced enzyme is derived from the difference of the dissociation rate constants.

Animals↗
PubMed1987

Chromosomal translocation and inverted duplication associated with integrated hepatitis B virus in hepatocellular carcinomas.

Integrated hepatitis B virus (HBV) DNA is found in hepatocellular carcinomas which develop in HBV carriers. Presented here are the results of analyses of four integrants that show chromosomal rearrangements associated with the integrated HBV DNA. Two clones (p4 and C15) were found to have large inverted repeating structures, each consisting of HBV genome along with flanking cellular sequences. The structure must have arisen by duplication of the primary integrant, including the flanking cellular DNA, followed by recombination within the viral DNA. One of the two viral arms in each clone joins to the other viral arm at the "cohesive end region." Two clones (DA2-2 and DA2-6) were found to have integrated HBV sequences, each flanked by cellular DNAs from different chromosomes (chromosome X joined to 17 and chromosome 5 joined to 9). They must be the products of cellular DNA translocations using the integrated HBV DNA as the switch point. The viral DNA in each clone is a continuous stretch of a single virus genome with one end in the cohesive end region. These complex structures seem to have been produced by activation of the cohesive end of an integrant viral genome, followed by its recombination with another chromosomal DNA.

Base Sequence↗