Biomedical subjects
Publications and source records attributed to M Shimizu.
YM-47141 and YM-47142 are new elastase inhibitor produced by Flexibacter sp. Q17897. These structures were elucidated by MS and NMR spectral analysis. YM-47141 and YM-47142 were the cyclic peptides containing tricarbonyl moiety hydrated on the center carbonyl carbon in DMSO-d6.
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Supraanular mitral valve replacement with a 29 mm CarboMedics prosthetic valve was performed for a 58-year-old patient of prosthetic valve endocarditis. He has received mitral valve replacement 2 years ago, and was admitted because of high fever and severe heart failure diagnosed mitral regurgitation due to valve dehiscence. An annular abscess was observed and the new 29 mm CarboMedics prosthetic valve was sutured to the left atrial wall approximately 10 mm above the original annulus in order to secure the firm suturings for valve implantation and to left the infected annulus intact. The patient, however, underwent reoperation because of valve dehiscence from atrial wall 6 months after surgery. Infectious abscess at the native mitral annulau was observed to be completely cured, and a mitral prosthesis was implanted at the annulus. The patient is discharged under satisfactory condition.
Despite substantial data on radioligand binding to the sigma receptor, neither the physiologic function nor the intracellular mechanism of this receptor is known. In this study, we examined the effect of sigma ligands on Ca++ influx induced by N-methyl-D-aspartate (NMDA) in single primary cultured rat frontal cortical neurons with fluorescence video microscopy. All sigma ligands tested reduced the NMDA-induced increase in intracellular Ca++ concentration ([Ca++]i) in a dose-dependent manner with IC50 values in the low micromolar range. Inhibition by haloperidol and (+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethyl-but-3-en-1-ylam ine hydrochloride (JO1784) was noncompetitive; but, exogenous glycine (100 microM) did not alter their IC50 values. In addition, haloperidol (1 microM) enhanced Mg+(+)-mediated inhibition of the NMDA-induced [Ca++]i increase (IC50 = 0.45 +/- 0.01 mM vs. an IC50 = 0.98 +/- 0.06 mM for Mg++ alone). Selective sigma receptor ligands (JO1784, (+)-pentazocine) caused a greater reduction of the sustained phase of the Ca++ response to NMDA, whereas haloperidol and DTG reduced both the initial and sustained phase of the response to a similar degree. The rank order of potencies for inhibition of both the sustained Ca++ response phase and (+)-[3H]SKF-10047 binding (Roman et al., J. Pharm. Pharmacol. 42: 439-440, 1989) were similar. These findings suggest that sigma 1 ligands indirectly modulate NMDA receptor complex function through sigma 1 receptors and that sigma ligands facilitate the desensitization of the Ca++ response to NMDA.
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Although Takayasu's arteritis may present a wide variety of signs and symptoms depending on the vessel affected, it is rarely associated with acute abdomen requiring emergency laparotomy. We report a case of Takayasu's arteritis that required several surgical interventions for mesenteric infarction, thoracoabdominal aneurysm, and proper hepatic artery aneurysm, all of which were noted in succession within a 1-year period. This is also the first report, to our knowledge, of a hepatic artery aneurysm caused by Takayasu's arteritis.
The correlation between the time-course changes in the serum concentration of myosin light chain 1 (ML-1) and left ventricular (LV) function was investigated in 37 patients with initial anterior acute myocardial infarction (AMI) after successful reperfusion. All patients were confirmed to have coronary arteries recanalized to TIMI grade 3 within 6 hours of AMI and patent arteries about 2 weeks after recanalization. LV function was assessed by left ventriculography. The patients were divided into two groups according to the time-course changes in the serum concentration of ML-1; 20 who showed an early peak of the serum ML-1 level within 24 hours and a late peak 3 to 5 days after recanalization (bimodal pattern: group B), and 17 who showed a single peak of the serum ML-1 level after recanalization (unimodal pattern: group U). The sum of ST elevation in an electrocardiogram before reperfusion and the additional ST elevation during reperfusion were both greater in group B than in group U (p < 0.1 and p < 0.05, respectively). The peak serum concentration of creatine kinase was significantly greater in group B than group U. LV dilatation was more extensive and the improvement of LV function was poorer in group B compared to group U.(ABSTRACT TRUNCATED AT 250 WORDS)
Left atrial function was assessed by transesophageal echocardiography in 8 patients with mitral stenosis and sinus rhythm (MS group), and 16 age-matched normal controls (C group). Pulsed Doppler findings of left upper pulmonary vein flow were classified into first and second forward waves during systole (S1, S2), forward wave during diastole (D), and backward flow during left atrial contraction (PVA). Peak velocity (P) and time-velocity integral (TVI) of each wave and acceleration and deceleration slope of S2 wave (S2-Ac, S2-Dc) were obtained. TVI-S2 and P-D in the MS group were significantly lower than those in the C group (TVI-S2: 4 +/- 2 vs 12 +/- 3 cm, P-D: 27 +/- 13 vs 41 +/- 12 cm/sec). S2-Ac and S2-Dc in the MS group were significantly higher than those in the C group (S2-Ac: 456 +/- 116 vs 323 +/- 118 cm/sec2, S2-Dc: 380 +/- 102 vs 165 +/- 48- cm/sec2). There were no differences in S1 and PVA. Lower TVI-S2 in the MS group suggests decreased reservoir function of the left atrium. Lower TVI-S2 in the MS group was caused by increased S2-Ac and S2-Dc which suggests increased left atrial preload and deterioration of left atrial compliance. Decreased P-D in the MS group reflects dysfunction of mitral valve opening.
The case of 70-year-old woman with cryoglobulinemia who underwent urgent operation for angina pectoris and mitral regurgitation is reported. Three bypass grafts and mitral valvuloplasty were performed under normothermic cardiopulmonary bypass with continuous warm blood cardioplegia. The postoperative course was uneventful. Normothermic cardioplegia requires further study as a technique for managing patients with cold autoimmune diseases such as cryoglobulinemia who require cardiopulmonary bypass.
A 70-year-old man performed graft replacement of descending thoracic aorta for chronic aortic dissection (DeBakey IIIb) with Hemashield arterial prosthesis. He also had coronary artery disease (LAD seg. 7.99% stenosis) and he had received PTCA prior to operation. He was administered anticoagulants such as Aspirin and Warfarin postoperatively. Two months after operation, he complained dyspnea and came back to our hospital. Chest X-ray showed left hemothorax. CT scan and aortogram could not revealed bleeding points such as pseudoanerysm at anastomosis site nor new dissection. He recovered after discontinued anticoagulants and drainage. If you need to use the anticoagulants after graft replacement with Hemashield, you should administer the anticoagulants about 14 days after operation. This is the first clinical report that hemothorax occurred two months after graft replacement with Hemashield.
A method to measure the absolute tricuspid regurgitant volume (TRV) using multigated equilibrium radionuclide angiocardiography is proposed. There was a significantly positive correlation between left and right ventricular stroke volume in 56 subjects with no regurgitation at rest (r = 0.881, p < 0.001) and during exercise (r = 0.884, p < 0.001), and each regression equation was obtained. Clinical studies were obtained 27 times in 22 patients with tricuspid regurgitation (TR). TRV was calculated by correcting right ventricular stroke volume using that regression equation. Patients with severe TR (grade III x IV classified from the pulsed Doppler) were well distinguished from patients with mild TR (grade I or II) by TRV. It is concluded that this method is well applicable to clinical study and useful in quantitative analysis of TR.
In order to evaluate 201Tl SPECT for the assessment of tumor viability after radiation therapy. Twenty rabbits were implanted with VX-2 tumor in the left femoral muscles and were classified into four groups as follows: normal control group (N), 20 Gy irradiated response group (A), 20 Gy irradiated non-response group (B), and 40 Gy irradiated group (C). Eight days after implantation, 201Tl SPECT and CT studies were performed to assess the changes in 201Tl uptake and tumor volume at 0, 1, 2, 3, and 4 weeks after single irradiation. Histologic specimens were also taken. In group N tumors continued to increase in volume, but 201Tl uptake showed a steady decrease after 2 weeks. In group A tumors continued to increase in volume, but 201Tl uptake showed a transient decrease at 2 weeks, then a steady increase. In group B tumors showed a transient increase in volume at 2 weeks, then a continuous decrease, but 201Tl uptake showed a continuous decrease throughout the study. In group C there was a continuous decrease both in volume and 201Tl uptake with the later more prominent. 201Tl uptake was decreased earlier than tumor volume both in group B and C, at one week that was significant (p < 0.01). 201Tl uptake by tumor reflects the burden of viable tumor on histology; therefore 201Tl SPECT is of great use in assessing the therapeutic effects on tumors.
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A 67-year-old woman was admitted to our hospital with a complaint of anterior chest pain on exertion. Auscultation disclosed a continuous murmur and exercise electrocardiography revealed positive ischemic ST change. Coronary angiography showed a large left coronary fistula and a small right coronary fistula into the main pulmonary artery. To evaluate the influence of the fistula on coronary circulation, we measured blood flow in the left anterior descending artery (LAD) and in the fistula artery using a 0.014 inch Doppler guide wire. Before surgery, blood flow in the LAD decreased during rapid atrial pacing (130 bpm) but that in the fistula remained constant. After the surgery, there was no remarkable decrease in blood flow in the LAD during rapid atrial pacing (130 bpm), and the preoperative reduction ratio was calculated as 24% compared with postoperatively. These findings suggest that coronary steal phenomenon was involved in myocardial ischemia in this patient.
Five beagles out of 11 dogs aged 7-10 years with benign prostatic hypertrophy (BPH) were implanted subcutaneously with pellets of the synthetic anti-androgen chlormadinone acetate (CMA) at a dose of 10 mg/kg bodyweight. The remaining six dogs (one beagle and five mongrel dogs) underwent bilateral orchidectomy. Changes in prostatic volume, histological findings in the prostate and the testis, and peripheral plasma levels of LH, testosterone and oestradiol-17 beta (E2) were assessed up until 24 and 4 weeks after CMA-implantation and orchidectomy, respectively. Measurements of the size of the prostate and biopsies of the prostate were performed by laparotomy. Mean prostatic volume had decreased to 71% and 41%, respectively, of its pretreatment volume, by 4 weeks after CMA-implantation and orchidectomy, and was 49% and 47%, respectively, of pretreatment volume at 12 and 24 weeks after CMA-implantation. The clinical signs of BPH, e.g. haematuria, resolved within 2 weeks after either treatment. When the prostate was examined histologically 4 weeks after either treatment, hardly any evidence of active secretion (e.g. glandular epithelium projecting markedly into the lumen), was observed in CMA-implanted dogs, alveolar diameter and height of the glandular epithelium had decreased markedly and the glandular lumen had become very small in the orchidectomized dogs. By 12 weeks after CMA-implantation, degenerative and atrophic glands were observed in the prostate nearly the same as at 4 weeks after orchidectomy. In the testis the number of germ cells in the seminiferous tubules decreased markedly after CMA-implantation. The mean level of plasma LH at 4 weeks after orchidectomy had increased to 14.9 ng/ml, twice the value before operation. The mean levels of plasma testosterone and E2 at 4 weeks after CMA-implantation had decreased to 0.7 ng/ml and 9 pg/ml from 1.5 ng/ml and 15 pg/ml, the values before treatment, respectively. CMA-implantation resulted in poor semen quality. The results indicate that CMA-implantation at a dose of 10 mg/kg results in the same prostate-shrinking effect as orchidectomy.
We have developed a new method for analysis of the interaction between lectins and biotin-derivatized oligosaccharides involving a biosensor based on surface plasmon resonance. Complex type asialo-bi-, tri-, and tetra-antennary oligosaccharides were quantitatively converted into their biotin derivatives by incubating them with 6-(D-biotinyl)-aminohexanoyl hydrazide. This method was also applicable to sialyl sugar chains without any removal of sialic acid residues. The reaction mixture could be directly injected onto the streptavidin pre-immobilized surface of a sensor chip without any purification because of its fairly low reagent/carbohydrate molar ratio. The amounts of sugar chains required for interaction analysis by this method were as low as 1 pmol. The binding specificities of Sambucus sieboldiana lectin, Maackia amurensis lectin, Ricinus communis agglutinin-120 (RCA120), and concanavalin A could be rapidly determined qualitatively by this method. Furthermore, kinetic analysis of the interaction between RCA120, and complex type asialo-bi-, tri-, and tetra-antennary oligosaccharides revealed that both the association rate constant and the dissociation rate constant (kdiss) decreased with increasing numbers of terminal galactosyl residues. Because the tendency observed for kdiss paralleled the elution order of these oligosaccharides on RCA120 immobilized affinity chromatography, kiss might hold the key to determination of the elution order on affinity chromatography.
It is discussed that oligopeptides extracted from the active centers of aminoacyl-tRNA-synthetases, peptidyl-transferases, and template-directed RNA polymerases can mimic the catalytic activities of each enzyme. Hairpin type primitive tRNAs with the anticodon at the 5' end were specifically aminoacylated from the cognate aminoacyladenylates in the above scheme. These results suggest that primitive RNA-protein interactions among oligomers of ribonucleotides and amino acids might have played an important role in the self-organization of the biomolecules in the early history of life.