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Biomedical subjects

K Nakai

Publications and source records attributed to K Nakai.

At least 253 records · Page 14Linked to original sources

Cerebral blood flow in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.

BACKGROUND AND PURPOSE: The precise mechanism of neurological symptoms with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) is still controversial. We investigated the correlation between strokelike episodes and cerebral blood flow in two patients with MELAS and discuss the pathogenesis of strokelike episodes with MELAS. SUMMARY OF REPORT: Cerebral dynamic computed tomography and cerebral angiography were used to measure cerebral circulation in the first case, that of a 20-year-old woman with MELAS. The second subject was a 13-year-old female who was studied with xenon-enhanced computed tomography. The cerebral blood flow studies were performed 3-72 hours after the onset of strokelike episodes. Serial cerebral angiography, dynamic computed tomography, and xenon-enhanced computed tomography showed vasodilation localized in the affected cerebral cortexes during strokelike episodes, without any reduction in regional cerebral blood flow. CONCLUSIONS: Our study suggests that the strokelike episodes associated with MELAS are different in origin from ischemic stroke.

Adolescent↗

Inhibitory effects of hyaluronan on neutrophil-mediated cartilage degradation.

The effects of hyaluronan on neutrophil-mediated cartilage degradation were studied in an in vitro model. Rat peritoneal neutrophils were incubated for up to 18 h with the neutralized cartilage of bovine nasal septa using N-formyl-L-methionyl-L-leucyl-L-phenylalanine combined with cytochalasin B, or opsonized zymosan, as a stimulation agent of neutrophils. Hyaluronan inhibited the neutrophil-mediated cartilage degradation by reducing the release of sulfated glycosaminoglycans from the cartilage. Inhibitory effects were dependent on concentration and molecular weight of hyaluronan. These results suggest that hyaluronan with a high molecular weight plays an important role in protecting the articular cartilage in inflamed joints from neutrophil injury.

Animals↗

Serial course of left ventricular function, perfusion and fatty acid uptake in the cardiomyopathic hamster.

To determine the relationship of metabolic and perfusion changes to alterations in ventricular function in the course of cardiomyopathy, we performed serial measurements of ejection fraction, myocardial perfusion, fatty acid uptake of 3-methyl-p[123I]-phenyl-pentadecanoic acid ([123I]3MPDA) and myocardial histology in Syrian hamsters genetically predisposed to the development of congestive cardiomyopathy (Bio T0-2) (n = 30) and normal age-matched control animals (Bio F1B) (n = 13). To obtain high-resolution information about the myocardium at the time of onset of the first noticeable decrease in ventricular function, a multitracer autoradiographic study using 99mTc-pyrophosphate, 201Tl and [14C]3MPDA was obtained at 90 days of age. Baseline ejection fraction recorded at 60 days averaged 60.3%; by 90 days, it decreased to 54.3% (p < 0.05), falling to 41.3% at 180 days (p < 0.01) and declining to 30% at the end of the study. A progressive increase in the extent of myocytolysis, fibrosis and calcification was seen in the histologic studies as the animals aged. The ratio of fatty acid-to-thallium uptake dropped from 0.51 +/- 0.09 to 0.45 +/- 0.11 (p < 0.01), which is in parallel with the reduction in ejection fraction. The thallium lung-to-heart ratio increased from 0.51 at 90 days to 0.59 at 270 days (p < 0.05), which corresponds to the worsening of cardiac function. The macroautoradiographic studies demonstrated slight uptake of pyrophosphate in the myopathic hamster hearts and minimal changes in the regional distribution of fatty acid compared to that of perfusion. We conclude that the decrease in ventricular function parallels the severity of myocytolysis and fibrosis. Although decreased fatty acid uptake was apparent at an early stage, the extent of the change is modest and is difficult to detect from external images.

Animals↗

[Pharmacokinetic study on aspoxicillin transfer into pulmonary and tracheal tissues].

Each of 36 patients who underwent tracheotomy for removal of malignant or benign tumors or for treatment of pneumothorax was infused with 2 g of aspoxicillin (ASPC, Doyle injection) intravenously over 1-hour period. ASPC concentrations determined at 1 postoperative time-point in tissues of the lung and trachea and in serum of each patient were analyzed pharmacokinetically to elucidate the transfer of ASPC to the thoracic tissues. The preventive effect of ASPC against postoperative infections was also investigated in 39 tracheotomy patients. 1. The analysis of ASPC concentrations in 36 patients with tracheotomy gave the following results; 1) The peak blood level (about 80 micrograms/ml) was attained at the end of infusion. The serum level then decreased with time to below about 10 micrograms/ml at 6 hours after the start of infusion, with an elimination half-life of about 1.4 hours, which was comparable to that in healthy adults. 2) Peak levels in the lung and tracheal tissues were achieved at about 30 minutes after the start of infusion, at levels of about 30 and 40 micrograms/g, respectively, which decreased to about 5 micrograms/g in both tissues at 6 hours after the start of infusion. 2. Thirty nine patients who were treated with ASPC before operation were examined for the preventive effect of ASPC against postoperative infections for 1 week after operation. No postoperative infection was noted in any patients and ASPC was found to be useful for prevention of postoperative infections. 3. No side effects or abnormal laboratory findings were noted in any patients. Based on the results of the transfer into the tissues of respiratory organs and preventive effect against postoperative infections, we have concluded that ASPC is useful for prevention of infections after thoracic operation.

Adolescent↗

[Detection of myocardial ischemia by 99mTc-Teboroxime myocardial SPECT: a comparison with 201Tl myocardial SPECT].

Exercise myocardial SPECT using 99mTc-Teboroxime was performed and the regions of ischemic area were compared with 201Tl myocardial SPECT in 8 patients with coronary artery disease. All patients had no evidence of previous myocardial infarction, and underwent bicycle ergometer exercise according to a standardized multistage exercise protocol. At peak exercise, 555 MBq 99mTc-Teboroxime or 75 MBq 201Tl was injected intravenously. After termination of exercise, images were obtained with a gamma camera rotating through a 180 degrees arc from 45 degrees right anterior oblique to 45 degrees left posterior oblique. The concordance of 99mTc-Teboroxime SPECT and 201Tl SPECT was 63% in ischemic region and 83% in normal region. Furthermore, one patient underwent dipyridamole infusion and 99mTc-Teboroxime SPECT was carried out. The images obtained by dipyridamole 99mTc-Teboroxime SPECT were equivalent to the images of exercise 201Tl SPECT. 99mTc-Teboroxime SPECT seems useful for the detection of the coronary artery disease. It was suggested that evaluation of the myocardial viability in acute phase of myocardial infarction can be possible by using 99mTc-Teboroxime SPECT.

Aged↗

[Newly developed blocking balloon catheter for PTA of internal carotid artery].

We have developed a new blocking balloon system for percutaneous transluminal angioplasty (PTA) of the internal carotid artery (ICA). A latex balloon (BALT) is attached on the top of a Superselector infusion-type catheter (TORAY) which is used as a blocking balloon catheter. It can be navigated into the distal part of the ICA under torque control as well as flow control by withdrawing the core wire. Our PTA procedure is as follows, 1) insert the sheath catheter 8-9 F in size, 2) insert the PTA balloon catheter (Accent balloon, Cook) with a blocking balloon catheter through the sheath catheter, 3) navigate the blocking balloon into the distal part of the ICA, 4) introduce the PTA balloon to the stenotic portion after occlusion of the distal ICA by the blocking balloon, 5) PTA, 6) wash the lumen of the ICA with saline, 7) deflate the blocking balloon and withdraw the system. We performed PTA for 5 ICA lesions in 4 cases and got successful dilatations for all of them without complications. Our blocking balloon system is useful for performing the PTA of the ICA safely.

Aged↗

Beta-naphthoflavone induction of a cytochrome P-450 arachidonic acid epoxygenase in chick embryo liver distinct from the aryl hydrocarbon hydroxylase and from phenobarbital-induced arachidonate epoxygenase.

Cytochrome P-450-mediated arachidonic acid metabolism in chick embryo liver microsomes was increased by both Ah receptor-dependent (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and beta-naphthoflavone) and independent (phenobarbital) P-450 inducers. Arachidonic acid epoxides and monohydroxyeicosatetraenoic acids were increased 9-12-fold. omega-1-OH arachidonic acid was also significantly increased by TCDD and beta-naphthoflavone while omega-OH arachidonic acid, the main metabolite in uninduced livers, was decreased by all three agents. The P-450s catalyzing the enhanced arachidonate metabolism in beta-naphthoflavone- and phenobarbital-treated liver were investigated in reconstituted systems containing wholly or partially purified P-450s. beta-Naphthoflavone induced formation of a 55-kDa P-450 selective for arachidonate metabolism and for epoxygenation in particular. This P-450 was purified (beta NFAA). It was found to be distinct from a 54.5-kDa beta-naphthoflavone-induced P-450 catalyzing aryl hydrocarbon hydroxylase and 7-ethoxyresorufin deethylase (designated NF1). Mean turnover numbers for arachidonate epoxygenase, aryl hydrocarbon hydroxylase, and 7-ethoxyresorufin deethylase were 11.2, 0.56, and 0.04, respectively, for reconstituted beta NFAA and 0.33, 11.8, and 2.4 for NF1. beta NFAA and NF1 also differed in chromatography elution characteristics and N-terminal amino acid sequences. Both were low spin, with carbon monoxide binding peaks at 448 nm. The phenobarbital-induced arachidonate epoxygenation was catalyzed by P-450 fractions containing the main 48- and 49-kDa phenobarbital-induced P-450s; fractions in which the 49-kDa P-450 predominated were the most active. Turnover numbers for arachidonic acid epoxygenation were not correlated with those for aminopyrine demethylation or 7-ethoxycoumarin deethylation for P-450s from phenobarbital-treated livers or with aryl hydrocarbon hydroxylase, 7-ethoxyresorufin deethylase, or 7-ethoxycoumarin deethylase for P-450s from beta-naphthoflavone-treated livers. Also, different P-450s catalyzed the epoxygenation and the omega-hydroxylation of arachidonic acid in both beta-naphthoflavone- and phenobarbital-treated livers. The findings support a physiologic role for P-450-induced arachidonate metabolism and provide a basis for a possible link between TCDD's induction of P-450 and alterations of cellular homeostasis.

Amino Acid Sequence↗

Expanding cranioplasty for craniosynostosis and allied disorders.

For early correction of craniosynostosis in the newborn or in early infancy, strip craniectomy may produce satisfactory results. For late correction, however, more radical cranial reconstruction procedures are essential in order to achieve adequate remodeling of cranial deformities and normalization of intracranial pressure. Craniosynostosis presents various types of cranial deformity, and different procedures for its correction have been reported. Expanding cranioplasty is presented for the increase of cranial volume and immediate correction of the cranial deformity. This cranioplasty can be applied not only for late correction of various types of craniosynostosis but also for other cranial deformities.

Craniosynostoses↗

MRI changes in embolized meningiomas.

Study of the MRI changes that occur after superselective embolization of hypervascular meningiomas with Gelfoam powder (5 cases) and polyvinyl alcohol (PVA) particles 150-250 microns in size (4 cases) has indicated that, after embolization, meningiomas showed loss of the signal void, decrease in gadolinium-DTPA contrast enhancement, and prolonged T1 and T2. Shortening of T1 and T2 was seen in two patients with Gelfoam-embolized meningiomas in whom CT showed pooling of iodinated contrast medium in the tissue. In vitro experimental data demonstrated that the shortening of T1 and T2 was due to the iodinated contrast medium.

Aged↗

The causes and clinical significance of exercise-induced silent myocardial ischemia evaluated by ischemic range and intensity with exercise Tl-201 myocardial SPECT.

We investigated the causes and long-term prognosis of exercise-induced silent myocardial ischemia (SMI) by means of exercise Tl-201 myocardial SPECT (Ex-SPECT) in 97 patients with effort angina or old myocardial infarction (OMI). These patients were proven to have significant stenosis by coronary angiography. The subjects were divided into three groups based on the presence or absence of Tl-201 redistribution or angina during exercise testing. Group one consisted of 34 patients who had redistribution on Ex-SPECT and angina during exercise testing: the painful myocardial ischemia (PMI) group. The second group consisted of 38 patients who had redistribution on Ex-SPECT, but no angina during exercise testing: the SMI group. The third group consisted of 25 patients who had no redistribution: the RD (-) group. The ischemic range and intensity were quantified by the defect volume ratio (DVR) and defect severity index (DSI), respectively. Comparison of the DVR and DSI values for the PMI and SMI groups revealed that the DVR and DSI values for the SMI group were lower than those of the PMI group. Also the prognosis of the SMI group tended to be worse than that of the RD (-) group. Thus, we concluded that the SMI and PMI group should receive identical treatment.

Aged↗

Lack of effect of islet amyloid polypeptide on hepatic glucose output in the in situ-perfused rat liver.

Islet amyloid polypeptide (IAPP), a novel peptide isolated from islet amyloid deposits in patients with insulinoma and non-insulin-dependent diabetes mellitus (NIDDM), has been reported to be cosecreted with insulin from pancreatic beta cells and to inhibit glucose uptake and glycogen synthesis in muscle tissue in vitro. We investigated the effects of the synthesized, rat-amidated form of IAPP on hepatic glucose output, and IAPP extraction, using an in situ flow-through perfusion system in rats to elucidate the actions of IAPP on the liver. The IAPP (10(-8) mol/L) alone had no effects on the hepatic glucose release. Infusion of 6 x 10(-11) mol/L glucagon alone resulted in an expected elevation in glucose production (30.0 +/- 1.7 mumol/35 min/g liver). Insulin (3 x 10(-10) mol/L) submaximally decreased the glucagon-stimulated glucose production to 73% (from 30.0 +/- 1.7 to 22.0 +/- 1.4 mumol/35 min/g liver; n = 7, P less than .01). A simultaneous infusion of 10(-8) mol/L IAPP did not influence the glucagon-stimulated glucose production (27.6 +/- 1.2 mumol/35 min/g liver) or the insulin-dependent inhibition of glucagon-stimulated glucose production (22.6 +/- 1.3 mumol/35 min/g liver). IAPP extraction by the liver in a single passage was minimal, in contrast to approximately 50% hepatic insulin extraction. These results indicate that IAPP does not play any important role in modulating glycogen metabolism in the liver.

Amyloid↗

A knowledge base for predicting protein localization sites in eukaryotic cells.

To automate examination of massive amounts of sequence data for biological function, it is important to computerize interpretation based on empirical knowledge of sequence-function relationships. For this purpose, we have been constructing a knowledge base by organizing various experimental and computational observations as a collection of if-then rules. Here we report an expert system, which utilizes this knowledge base, for predicting localization sites of proteins only from the information on the amino acid sequence and the source origin. We collected data for 401 eukaryotic proteins with known localization sites (subcellular and extracellular) and divided them into training data and testing data. Fourteen localization sites were distinguished for animal cells and 17 for plant cells. When sorting signals were not well characterized experimentally, various sequence features were computationally derived from the training data. It was found that 66% of the training data and 59% of the testing data were correctly predicted by our expert system. This artificial intelligence approach is powerful and flexible enough to be used in genome analyses.

Algorithms↗

A possible involvement of central atrial natriuretic peptide in cerebral cortical microcirculation.

The possible involvement of atrial natriuretic peptide (ANP) in cerebral cortical microcirculation was investigated in rats by means of laser-Doppler flowmetry and immunohistochemistry. In the laser-Doppler study, local cerebral blood flow (LCBF) changes after the administration of 10(-6) to 10(-8) mol/LANP solution or vehicle (saline solution) as an intracortical injection for 5 minutes were continuously monitored throughout the 30 minutes of the study and were expressed as percentages of preinjection values represented as 0%. The administration of 10(-6) to 10(-8) mol/LANP caused a significant decrease in LCBF; the onset of LCBF responses occurred within a few minutes after the start of the injection and the decrease in LCBF reached the maximum level within 7 to 10 minutes after the completion of the administration, after which LCBF gradually recovered. In the immunohistochemical study, no specific ANP immunoreactivity was found associated with the intraparenchymal blood vessels; however, ANP-immunoreactive neurons were observed primarily in the hypothalamus and septum, in which high concentrations of ANP-containing neurons have been identified. The data from the laser-Doppler study suggest that central ANP may produce a vasoconstriction of the intraparenchymal blood vessels, regardless of whether through direct action on these vessels or through the mediation by some system in the central nervous system. Because there is no evidence for ANP-containing nerves around these vessels, the role of central ANP in the cerebral circulation must await identification of the source of perivascular ANP.

Animals↗

Development of analytical methods to evaluate SFH.

For the determination of stroma content in SFH, two analytical methods were developed, the HPLC-UV for phospholipids and the enzyme immunoassay for blood group antigen. These analytical methods were applied to evaluate three representative SFH preparations. The 36,000 x g centrifugation method was shown to contain higher amount of stroma components. On the other hand, the BMM-40 nm and the ultrafiltration method with a 100 kd membrane was shown to remove more than 99.7% of phospholipids and almost all of blood group antigen from hemoglobin solutions. These results demonstrated that these analytical methods were very useful in evaluating any highly purified hemoglobin solutions.

ABO Blood-Group System↗

[Pitfalls of endovascular treatment for cerebral aneurysms].

Seventeen cases of unclippable aneurysms were treated by the endovascular balloon technique. Nine of them involved the anterior circulation, and eight involved the posterior circulation. Eleven of them were treated by parent artery occlusion with detachable balloons. Three were treated by endosaccular balloon embolization, and three cases combined with AVMs were occluded using ethylene vinyl alcohol copolymer (EVAL) including feeding arteries of the AVMs. Embolic complications occurred in one case of an IC bifurcation giant aneurysm treated by parent artery occlusion. Ischemic complications also appeared in two cases of aneurysms treated by endosaccular balloon embolization. In one case, the thrombus in the aneurysm propagated into the parent artery and occluded it later. In another case, the displaced balloon had obliterated the parent artery 6 hours after the embolization. Parent artery occlusion is a safe way to treat internal carotid giant aneurysms. However, endosaccular treatment still has some problems, i.e., 1) maintaining the balloon's position to preserve the parent artery, 2) balloon migration into the clot, 3) rupture of the aneurysm during or after treatment. Our studies indicate that endosaccular balloon embolization is still a high risk procedure and should be used only in selected cases, until new embolic agents, such as detachable coils, become available.

Adult↗

[Increased serum levels of human cardiac myosin light chain 1 in patients with renal failure].

In this study, we measured cMLC1 concentration in serum and urine from patients with acute myocardial infarction (AMI), chronic renal failure (CRF), and various grades of renal dysfunction (RD) in comparison with normal controls, by using enzyme immunoassay (EIA) with monoclonal antibody, and attempted to elucidate the mechanism of increased serum level of cMLC1 in patients with renal failure. The serum level of cMLC1 of CRF patients under maintenance hemodialysis (HD) was 20.3 +/- 19.6 ng/ml, markedly higher than normal controls (0.54 +/- 0.55 ng/ml). The patients with RD and CRF under conservative therapy had higher serum cMLC1 level than normal controls especially in advanced CRF, while each value not correlating with their creatine clearance (Ccr). cMLC1 in urine was detectable in only two cases with AMI accompanied with CRF or RD. In addition, immunohistological studies of renal biopsy specimens from RD patients did not show cMLC1 deposits in glomerulus. These results suggest that cMLC1 is assumably filtered through the glomerulus, and then absorbed in the renal tubule.

Humans↗

Expert system for predicting protein localization sites in gram-negative bacteria.

We have developed an expert system that makes use of various kinds of knowledge organized as "if-then" rules for predicting protein localization sites in Gram-negative bacteria, given the amino acid sequence information alone. We considered four localization sites: the cytoplasm, the inner (cytoplasmic) membrane, the periplasm, and the outer membrane. Most rules were derived from experimental observations. For example, the rule to recognize an inner membrane protein is the presence of either a hydrophobic stretch in the predicted mature protein or an uncleavable N-terminal signal sequence. Lipoproteins are first recognized by a consensus pattern and then assumed present at either the inner or outer membrane. These two possibilities are further discriminated by examining an acidic residue in the mature N-terminal portion. Furthermore, we found an empirical rule that periplasmic and outer membrane proteins were successfully discriminated by their different amino acid composition. Overall, our system could predict 83% of the localization sites of proteins in our database.

Bacterial Outer Membrane Proteins↗