Biomedical subjects
Publications and source records attributed to T Yasuda.
In an experimental model of peritoneal infection by cephalosporinase- (Ia and Ic) producing bacteria in mice, the reduction of cefoxitin, cefmetazole, and cefazolin concentrations in peritoneal fluid was observed in the mice infected with the Ia enzyme producer, whereas cefbuperazone concentrations were not reduced.
To determine whether renal blood flow can be measured by positron-emission tomography (PET) during constant infusion of rubidium-82 (82Rb) using a steady-state kinetic model, studies were performed in 10 dogs at control (n = 10), during mild flow reduction (n = 7), during severe flow reduction (n = 10), and after reperfusion of the kidney (n = 3). PET data were quantified to determine mean concentration of 82Rb (Ct) in each transverse section of the kidney. The arterial concentration (Ca) of 82Rb was measured by well counting of arterial blood samples during the equilibrium scan. 82Rb renal uptake (Ct/Ca) correlated nonlinearly with microsphere renal blood flow according to a steady-state kinetic model (r = 0.90). 82Rb estimated flow was 3.16 +/- 1.36 ml X min-1 X g-1 at control and 1.56 +/- 0.57 and 0.37 +/- 0.59 during mild and severe flow reductions, respectively. Microsphere determined flow was 2.89 +/- 0.77 ml X min-1 X g-1 at control, 1.58 +/- 0.42 at mild reduction, and 0.27 +/- 0.49 at severe reduction. In the occlusion and reperfusion model, the 82Rb estimated flow during occlusion was 0.21 +/- 0.15 ml X min-1 X g-1 and on reperfusion went up to 2.13 +/- 1.08. The contralateral kidney demonstrated reductions in the 82Rb estimated flow of 3.02 +/- 1.62 ml X min-1 X g-1 (63%) and 2.92 +/- 0.89 (61%) during mild and severe flow reductions, respectively. We conclude that PET with 82Rb permits serial quantitative assessment of renal flood flow.
Twenty-nine patients with acute myocardial infarction were treated with recombinant human tissue-type plasminogen activator (rt-PA). The incidence of acute coronary reocclusion and its prevention by a maintenance infusion of rt-PA were studied. Intravenous rt-PA was given at a rate of 0.4 to 0.75 mg/kg over 60 to 120 min after angiographic documentation of complete coronary occlusion. Reperfusion was accomplished within 1 hr in 24 of 29 patients (83%) and was associated with a decrease of the plasma fibrinogen level by 20%. In a first group of 13 patients, 11 of whom were successfully reperfused, prevention of reocclusion was attempted with heparin anticoagulation. However, acute reocclusion within 1 hr after cessation of rt-PA was demonstrated angiographically in five of these patients (45%). Quantitative angiographic analysis indicated that acute reocclusion only occurred in patients with 80% or greater residual stenosis. In patients with less than 80% residual stenosis, heparin anticoagulation was sufficient to maintain patency during the hospital stay in four of five patients. In a second group of patients (n = 16), 13 of whom underwent reperfusion with intravenous rt-PA, seven demonstrated a residual stenosis of 80% or greater. These patients were given heparin and, in addition, 10 mg of rt-PA per hour for 4 hr. None developed acute angiographic reocclusion or clinical signs of reocclusion during the hospital stay. Repeat angiography at 10 to 14 days confirmed persistent patency in six of the seven patients. The maintenance infusion resulted in only a moderate additional drop in fibrinogen, while a steady-state plasma rt-PA level of 750 +/- 250 ng/ml was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)
The Fab fragments of antimyosin antibodies, labeled with 99mTc, were used in the scintigraphic examination of 30 patients with myocardial infarction. The ability to detect necrosis and determine its extent from the antimyosin scan were compared with the results of quantitative regional wall motion analysis by contrast ventriculography at 10 to 14 days and 99mTc-pyrophosphate imaging. Antimyosin images recorded by planar and single photon-emission computed tomography (SPECT) delineated areas of myocardial necrosis in 27 of 30 patients (90%) compared with a 91% sensitivity of pyrophosphate in 21 of 23 patients. Infarct size was determined by both antimyosin and pyrophosphate SPECT images. Results by both techniques showed a significant correlation with computer-derived hypokinetic segment length (r = .79 for both, p = .002) and peak creatine kinase (r = .9 for both, p less than .01). Although sensitivity for and correlations with markers of necrosis were similar with both techniques, infarct size by pyrophosphate SPECT was 1.7 times larger than infarct size by antimyosin SPECT (p less than .01). Certain zones in the infarct area were differentially labeled; the nature and irreversibility of injury within these zones remains to be clarified.
The activity of stimulatory guanine nucleotide regulatory protein (Ns) in the erythrocyte membrane was assayed by the reconstitution method using plasma membrane of cyc S49 mouse lymphoma cells in 18 patients with type I pseudohypoparathyroidism (PHP-I), 2 with pseudopseudohypoparathyroidism (PPHP) and 30 normal subjects, in parallel with other clinical parameters. The Ns activity as expressed by per cent of pooled standard (mean +/- SE) was 78.9 +/- 6.1 in PHP-I patients, which was significantly lower (P less than 0.01) than the value in normal subjects, 99.5 +/- 2.4. In PHP-I patients, the Ns activities (Y) were in significant correlation with three clinical parameters examined (X), i.e., with body height in standard deviation score from the mean of the normal population at the corresponding age, Y = 89.4 + 10.4X (r = 0.616, P less than 0.01); with urinary cAMP excretion in relation to creatinine [cAMP(nmol)/Cr(mg)], Y = 56.3 + 7.2X (r = 0.501, P less than 0.05); and with TSH levels in plasma (microU/ml), Y = 129 - 3X (r = 0.639, P less than 0.01). The Ns activities of PPHP were as low as 53.8 and 60.0. The decrease of Ns activity in the cell membrane may be implicated in the development of the clinical symptoms such as short stature, decrease in urinary excretion of cAMP and latent or manifest primary hypothyroidism in PHP-I and possibly in skeletal abnormality in PPHP.
The metabolism of 1-phenyl-2-(N-methyl-N-furfurylamino)propane (furfenorex) was studied in the rat in vivo and in vitro. Nine metabolites with only traces of the unchanged drug were obtained from urine after oral administration of furfenorex to rats. The major metabolite was an acidic compound, isolated and identified as 1-phenyl-2-(N-methyl-N-gamma-valerolactonylamino)propane. Amphetamine, methamphetamine and their hydroxylated metabolites were excreted as minor metabolites. Metabolites excreted in two days after administration of the drug amounted to about 20% of dose. The acidic metabolite, a major metabolite in vivo, was not detected after incubation of furfenorex with rat-liver microsomes. The major metabolic routes of furfenorex in vitro were N-demethylation and N-defurfurylation which produced 1-phenyl-2-(N-furfurylamino)propane (furfurylamphetamine) and methamphetamine, respectively. The formation of furfurylamphetamine and methamphetamine were catalysed by rat-liver microsomes supplemented with NADPH and O2, and were inhibited by either SKF 525-A or CO. The formation of both metabolites were inhibited by 2-methyl-1,2-bis-(3-pyridyl)-1-propanone (metyrapone), but not by 7,8-benzoflavone. They were enhanced by pretreatment of rats with phenobarbitone, but not with 3-methylcholanthrene. These data suggested that N-demethylation and N-defurfurylation of furfenorex were mainly mediated by cytochrome P-450 but not cytochrome P-448.
The antibacterial activity of 5-fluorouracil, an antineoplastic agent, was found to be enhanced by piperacillin, a beta-lactam antibiotic, resulting in a synergism. It was considered that the synergism was caused by an increase of 5-fluorouracil uptake into the bacterial cell. On the other hand, amount of piperacillin bound to penicillin binding protein (PBP) did not change when 5-fluorouracil was added. The morphological change of the cell was due to the 5-fluorouracil when synergism appeared between 5-fluorouracil and piperacillin.
The pharmacokinetics of each drug on the concomitant administration of piperacillin (PIPC) and cefazolin (CEZ) or cefoperazone (CPZ) were studied in rabbits. When rabbits received the consecutive drip infusion administration of CEZ (0.71 mg/kg/minute) and PIPC (1.38 mg/kg/minute) and likewise of CPZ (0.72 mg/kg/minute) and PIPC (1.54 mg/kg/minute) for 1 hour, respectively, the serum half-lives of CEZ and CPZ were respectively prolonged about 1.8 and 1.6 times during drip infusion of PIPC than administered alone. However, when the sequence of administration were reversed, the serum levels of PIPC were not affected by the consecutive drip infusion administration of CEZ and CPZ. To study these findings in detail, the single intravenous dose of 20 mg/kg of CEZ and CPZ were administered under drip infusion of PIPC (2.65-2.93 mg/kg/minute). The serum half-lives of CEZ and CPZ were also prolonged about 5.4 and 1.9 times, respectively, whereas urinary excretion of CEZ, and urinary and biliary excretion of CPZ were reduced by PIPC. Moreover, when the single intravenous dose of 20 mg/kg of PIPC were administered under drip infusion administration of CEZ (0.96-2.60 2.60 mg/kg/minute), the pharmacokinetics of PIPC was not affected by the presence of CEZ. However, under drip infusion administration of CPZ (2.60-2.70 mg/kg/minute), the PIPC serum half-life was prolonged about 1.4 times, and biliary excretion of PIPC was reduced but urinary excretion was not. From the results of renal clearance experiments, tubular secretion appeared to be the predominant mechanism of renal elimination for these three drugs. These results indicate that PIPC influences the pharmacokinetics of both drugs by the competitively inhibiting tubular secretion in CEZ, and tubular secretion and hepatic transport system in CPZ. Therefore, in this respect PIPC seems to have probenecid-like action.
Liver tumors were observed in 2 South American lungfish (Lepidosiren paradoxa) and in 1 African lungfish (Protopterus amphibius) kept in 3 different aquariums in Japan for 2-5 years. In the first case a single, large nodule (70 X 60 X 55 mm) in the liver had been noted externally as a swelling 1 year prior to death. In the second case 2 rounded nodules (25 X 15 X 15 mm and 15 X 10 X 10 mm) were incidentally found at autopsy. In the third case, which also demonstrated abdominal swelling for 1 year preceding death, 2 green nodules (50 X 50 X 40 mm and 17 X 17 X 17 mm) were found in the liver together with multiple metastatic lesions. Histologically, variation was evident from tumor to tumor, even within the same animal. The most common histologic type was typical trabecular hepatomas. Admixtures of glandular or papillary structures were noted in some tumors. A region of poorly differentiated hepatocellular carcinoma with spindle-shaped cells in a sheetlike arrangement was noted in one case. The cause of these tumors is unknown. Since liver tumors were discovered at relatively high incidence (3/14 autopsied cases, including 6 species), lungfish seem to be predisposed to the development of liver tumors.
A high resolution PET-HEADTOME III has been employed to quantitate regional cerebral hemodynamics and metabolism in gliomas using O-15 and 18FDG tracers, and to evaluate histological malignancy preoperatively. Hemodynamic and metabolic indices of regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen consumption (rCMRO2), oxygen extraction (rOEF), and glucose consumption (rCMRGl) were studied on thirteen preoperative gliomas involving one recurrent case. Regions of interest (ROIs) on PET were placed over the corresponding lesions in CT scans. In high grade gliomas, ROIs were also focused on the corresponding parts of central low density area, contrast enhanced area, and peritumoral low density area. rCBF and rCBV were variable and unrelated in both low and high grade gliomas. rCMRGl values were 5.99 +/- 3.99 mg/100 ml/min for high grade gliomas, and 3.01 +/- 0.48 mg/100 ml/min for low grade gliomas. Lesions with high uptake of radioisotope were proved to be high grade gliomas. lesions with low uptake being low grade gliomas. In comparison with the contralateral gray matter around the sylvian fissure, rCBV was significantly higher(p less than 0.02) in high grade gliomas, and rCMRGl was lower (p less than 0.05) in low grade gliomas. rCMRO2 and rOEF values were reduced markedly (p less than 0.01) in both low and high grade gliomas. These results support that anaerobic glycolysis increased with malignancy in the metabolism of gliomas. The hemodynamics and metabolism of central low density area and peritumoral low density area reflect the pathophysiological state of necrosis and edema respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
A patient with secondary (sporadic type) hypokalemic periodic paralysis with relative hypertension had reninism with a high concentration of plasma angiotensin I (ANG-I) but no hyperaldosteronism or high angiotensin II value. Angiotensin-converting enzyme (ACE) activity was usually normal. Results of other hormonal analyses were also normal. However, the glomerular filtration rate and filtration fraction of the kidneys were greatly elevated. Despite severe hypokalemia, the patient's potassium clearance was high. No evidence of distinct hyperplasia of the juxtaglomerular cells was obtained. These results suggest that decreased affinity of ACE to the substrate ANG-I (so-called ACE dysfunction syndrome) produced the reninism and high concentration of plasma ANG-I, and that the latter induced an increase in the glomerular filtration rate of the kidneys with sequential occurrence of secondary hypokalemic periodic paralysis.
Monoclonal antibody against tumor-associated antigen (TAA) expressed on bovine leukemia cells was conjugated to liposomes containing adriamycin (ADM), and the specificity and therapeutic effects of the conjugates were examined in vitro and in vivo using a TAA-positive bovine leukemia cell line as the target tumor. In vitro studies with the TAA-positive cell line clearly indicated that the antibody-conjugated liposomes containing ADM exerted selective effects on TAA-positive cells in the inhibition assay of 3H-thymidine incorporation. Three injections of liposomes containing ADM (4 mg/kg) into tumor-bearing nude mice significantly inhibited the tumor growth and the therapeutic effect of the antibody-conjugated liposomes was far greater than that of normal mouse IgG-conjugated liposomes as assessed in terms of tumor size.
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A rare case of primary interhemispheric subdural abscess is reported. This 13 year old boy, who had had high fever for 2 days, was brought into the hospital by an ambulance. He was disoriented and mild stiffness of the neck was noted. A Jacksonian seizure that began in the left leg occurred immediately after admission. The initial CT scan showed no apparent abnormality. His clinical signs and spinal fluid findings showing slight monocytic response and normal sugar content suggested viral meningo-encephalitis. The patient was given steroid and glyceol to control the intracranial pressure and antibiotics was also given. The convulsions disappeared with anticonvulsants and the patient became afebrile on the 7th hospital day. He was discharged on the 53rd hospital day without any neurological deficit. But, he was re-admitted because of recurrence of the convulsion 29 days after the discharge. The CT scan revealed an interhemispheric (rt parafalcial) abscess and the drainage of abscess was performed through a craniotomy. The post-operative course was satisfactory and he was discharged on 33rd post-operative day. It is easy to diagnose the primary interhemispheric subdural abscess on CT scan at the advanced stage. However, it may be difficult to make definite diagnosis at its acute phase and it is important not to miss some characteristic clinical features of the interhemispheric abscess that can be safely cured by appropriate surgical treatment.
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A technique for the semiautomatic calculation of left ventricular volumes from multigated blood-pool tomograms (MGBPT) was tested in a series of 12 patients undergoing contrast ventriculography within 48 hr of gated tomography. The parameters necessary for the calculation of volume were developed in a chest phantom study performed with a series of 99mTc-filled balloons representing the right and left ventricles. The images were analyzed for volume using a percentage of peak count-threshold of the left ventricular balloon. This technique resulted in a correlation of r = 0.99 of the calculated to the true phantom volumes (y = 0.87x + 27.4, p less than 0.01, s.e.e. = 7.87 ml). The patient studies were recorded at 16 frames/cardiac cycle at each of 60 angles over a 360 degree rotation. Reconstructed data were presented in an endless loop cine format producing a set of sequential "beating tomographic slices" in the transverse, apical four-chamber, short-axis, and long-axis oblique views. Measurements of end systolic volume (y = 0.79x + 30, r = 0.93, p less than 0.001, s.e.e. = 24 ml), end-diastolic volume (y = 0.63x + 60, r = 0.94, p less than 0.0001, s.e.e. = 20 ml) and ejection fraction (y = 0.88x - 0.02, r = 0.92, p less than 0.001, s.e.e. = 0.08) determined from the semiautomated volume method correlated well with those determined by left ventricular contrast angiography. A qualitative comparison of MGBPT, planar imaging, and left ventricular angiography in 12 patients revealed that the visual assessment of wall motion using the 16-frame tomographic slices had significant advantages over planar and single plane angiographic data in the identification of inferior, basal, and septal wall motion abnormalities as well as the extent of involvement by aneurysm formation. A quantitative comparison of wall motion in the long-axis oblique view of the MGBPT to the RAO 30 degree ventriculogram (y = 0.74x + 8.7, r = 0.82, p less than 0.0001, s.e.e. = 14%) confirmed the qualitative similarity of these two views. We conclude that MGBPT is promising as a method for accurately measuring left ventricular volumes and assessing regional wall motion.
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