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Biomedical subjects

T Asakura

Publications and source records attributed to T Asakura.

At least 199 records · Page 11Linked to original sources

Image analysis studies of the degree of irreversible deformation of sickle cells in relation to cell density and Hb F level.

We analyzed, quantitatively by image analysis, the degree of irreversible deformation of red cells (SS cells) from patients with homozygous sickle cell disease, and studied the relationships among the degree of irreversible cell deformation, cell density, and Hb F level. SS cells from 25 patients (aged 1-36 years) whose Hb F levels ranged from 2.5% to 40.0%, were fully oxygenated and then were separated into four fractions by density centrifugation. Every fraction was studied for morphology and Hb F content. We found that the irreversible deformation of SS cells from the circulation occurred mainly by elongation and that the degree of elongation was extremely variable. We also found that in the cells of patients with Hb F levels < 20% the degree of irreversible elongation increases as cell density increases, suggesting that dehydration occurs concomitantly with irreversible elongation. Statistical analysis (Student t test) indicated that there were significant differences (P = 0.008 or < 0.001) in the degree of elongation among density-fractionated SS cells from patients with Hb F < 20%, although there was no significant difference (P > 0.1) among those from patients with Hb F > or = 20%. We also found that cell density increased as Hb F level of the density fraction decreased in all patients with Hb F < 20% but not always in those with Hb F > or = 20%. This suggests that cells with lower Hb F levels are selectively susceptible to dehydration. Furthermore, we found that the mean degree of irreversible elongation decreases linearly with increasing levels of Hb F and reaches the normal range at 21-24%. Since the degree of irreversible deformation of SS cells quantified by image analysis is directly related to cell density, and inversely to Hb F levels, mechanical stress or membrane damage caused by Hb S polymerization may be an important factor in the formation of dense cells in vivo.

Adolescent↗

Diminution of biological reactivity of ethanol by changing the solution structure by weak ultrasonication.

The weak ultrasonication (40 kHz, 12 mW, 1 week) of ethanol solutions was found to reduce stimulation of the senses of smell and taste by the ethanol on the basis of blind tests with an aqueous ethanol solution (33.0% w/v) and an immature distilled spirit (25.0% v/v). Experiments on mice also demonstrated that a treated aqueous ethanol solution had a weaker depressant effect on the central nervous system, as evaluated by the relative frequency with which mice regained the righting reflex at a dose of either 4.0 or 4.5 g/kg (p < 0.05 or p < 0.01, respectively) and by the reduction in rectal temperature at a dose of 5.0 g/kg (p < 0.05) soon after ethanol administration. Analyses of both the ethanol concentration by head-space gas chromatography and the free radicals by electron spin resonance spectrometer failed to reveal any chemical changes in aqueous ethanol solutions subjected to weak ultrasonication. However, measurement of the spin-lattice relaxation time (T1) of the 2H of water molecules by 2H-NMR showed that the treatment slightly accelerated the thermal motion of water molecules in the solutions. Treated solutions were also found to have a slightly higher density than untreated ones. These physical data demonstrate that weak ultrasonication induces a structural change, such as a more compact and homogeneous structure by changing the microdynamic behavior of the solution. These biological and physical studies suggest that only a slight structural change in an ethanol solution induces a marked change in the biological reactivity of ethanol without any chemical modification of the solution itself.

Adult↗

Transcranial magnetic stimulation excites the root exit zone of the facial nerve.

The actual site of excitation of the facial nerve by transcranial magnetic stimulation was investigated in five patients with hemifacial spasm who underwent microvascular decompression. The facial nerve was stimulated preoperatively and intraoperatively by transcranial magnetic stimulation and intraoperatively by electrical stimulation at its root exit zone with a minimum of surgical invasion of the facial nerves. The onset latency of compound muscle action potentials recorded from the nasalis muscle was 5.06 +/- 0.44 ms by magnetic stimulation and 5.08 +/- 0.43 ms by electrical stimulation. The latency difference was 0.06 +/- 0.08 ms. Therefore, transcranial magnetic stimulation was basically the same as electrical stimulation in onset latency. From this study, it appears that the root exit zone of the facial nerves is stimulated by transcranial magnetic stimulation.

Electrodes↗

[Surgical results of postinfarction ventricular septal rupture].

Between 1981 and 1991, 17 consecutive patients underwent surgical repair of postinfarction ventricular septal rupture (VSR). 15 patients were operated upon during acute phase after the onset of VSR. Two patients were operated upon six weeks or more after the onset. Overall hospital mortality was 43% in the reviewed group. Our experience suggested that the number of the patients over 70 years of age increased and prevalence in VSR associated with the multivessel coronary artery disease was recognized. Despite improved surgical techniques and enhanced myocardial protection, our experience with surgical treatment of VSR was not as successful as we had hoped. Delay of operation is likely to produce hemodynamic instability and may increase operative mortality. In conclusion, the preoperative mechanical and pharmacological support should be performed, even if the patient is not so critically ill, and the earlier operation might lead to more favourable results in the surgery of the postmyocardial infarction ventricular septal rupture. In addition, preoperative coronary angiography for the precise evaluation of the coronary artery lesions might contribute to better results in the late phase of postoperative period.

Aged↗

[Retrograde systemic venous perfusion with selective jugular cannulation].

46 patients underwent surgery for the ascending aorta and the aortic arch using continuous hypothermic retrograde systemic venous perfusion (RSVP). Good cerebral protection has been obtained by this method in most patients including four in whom periods of retrograde perfusion exceeded 90 minutes (the longest 140 min). In first 19 patients retrograde perfusion was performed through conventional caval cannulae, but one of them sustained serious neurological damage despite a relatively short duration of retrograde perfusion probably due to impediment of retrograde flow to the brain with venous valves at the jugular-subclavian junction. Then we have developed a new technique that employs a cavoatrial cannula inserted selectively into the internal jugular vein beyond the valve at the venous angle and have applied this technique in last 27 patients.

Adult↗

[A juvenile male prolactinoma: a case report].

Male prolactinomas often become voluminous and invasive, and also show higher serum prolactin levels due to delay of diagnosis. We experienced a case of prolactinoma in a 15-year-old boy. He was admitted with a complaint of visual disturbance. CT and MRI showed intra- and suprasellar mass with a ring enhancement and niveau formation suggesting intratumoral hemorrhage. By the right subfrontotemporal approach, subtotal tumor removal was performed, and intratumoral hemorrhage was identified. Histological examination confirmed the existence of chromophobe adenoma and, furthermore, immunohistochemical study revealed the existence of a prolactinoma. The size of the tumor gradually diminished with the administration of bromocriptine, and serum prolactin levels returned to normal value during the postoperative course. Among all cases of prolactinomas reported in previous medical literature only 23 cases of patients under 20 years old have been reported. The authors analysed our case of prolactinoma along with other infrequent cases where intratumoral hemorrhage was especially noticeable.

Adolescent↗

[Surgical results in diabetics undergoing coronary artery bypass grafting].

Diabetes mellitus is a well-known risk factor in the patients undergoing coronary artery bypass grafting (CABG) and with increasing frequency diabetic patients are referred for CABG. From the fact that the arteriosclerosis is more diffuse and advanced in patients with diabetes, the presence of the diabetic state might be expected to be at risk for CABG. We retrospectively evaluated the surgical results in 91 patients with diabetes mellitus operated on from January, 1985, to June, 1991, compared with a control group of 339 patients during the same period. Compared with nondiabetic patients, diabetic patients had more extensive coronary artery disease and, therefore, received the more number of grafts per patient. However, no difference was noted in the incidence of operative mortality, morbidity and postoperative complication. The incidence of postoperative sternotomy infection was slightly higher, if not statistically significant, in the diabetic patients. Our study demonstrates that patients with diabetes mellitus can be operated on relatively safely.

Aged↗

Histochemical demonstration of NADPH-diaphorase activity, a marker for nitric oxide synthase, in neurons of the rat pancreas.

To clarify the role of nitric oxide (NO) in the pancreas, we histochemically investigated NADPH-diaphorase, a marker for NO synthase, in the rat pancreas. NADPH-diaphorase activity was localized in the neurons and endothelium of vessels. The nerve fibers with NADPH-diaphorase activity were observed in both the exocrine and the endocrine pancreas associated chiefly with the vascular systems. Most nerve cell bodies (98.5%) within the pancreatic parenchyma showed strong activity for this enzyme. These results suggest that NO may participate in the hemodynamic control of the pancreas and in the neuronal regulation of pancreatic exocrine and endocrine functions.

Amino Acid Oxidoreductases↗

12(R)-hydroxyeicosatetraenoic acid synthesis by 3-methylcholanthrene- and clofibrate-inducible cytochrome P450 in porcine ciliary epithelium.

Porcine ciliary epithelial microsomes synthesized 12[S]-hydroxy-5, 8, 10, 14-eicosatetraenoic acid (12[S]-HETE) from arachidonic acid by a membrane-bound lipoxygenase and 12[R]-isomer by the cytochrome P450-dependent monooxygenase system. The activity to form 12(R)-isomer was markedly enhanced by 3-methylcholanthrene and clofibrate. Both basal and induced levels of 12(R)-HETE synthesizing activity were considerably higher in nonpigmented epithelial cells than in pigmented cells of the ciliary processes. The induced activity was suppressed by polyclonal antibodies raised against purified cytochrome P450 IA1 and NADPH-P450 reductase but not by substrates for clofibrate-inducible omega/omega-1 hydroxylases (P450 IVA-mediated). These results suggest that 12(R)-HETE synthesis by porcine ciliary microsomes may be mediated by a cytochrome P450 of the IA family.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

The application of 1H NMR chemical shift calculations to diastereotopic groups in proteins.

We have calculated chemical shifts for a range of diastereotopic protons in proteins (i.e. methylene protons, and the methyl groups of valine and leucine residues), using a recently optimised method for chemical shift calculation. The calculations are based on crystal structure coordinates, and have been compared with experimental stereospecific assignments. The results indicate that chemical shifts can be used to suggest stereospecific assignments with about 80% probability of being correct, in cases where both the experimental and the calculated chemical shift differences between a pair of diastereotopic protons are greater than 0.3 ppm. Inaccurate calculations are shown to be caused in most cases by differences between crystal and solution structures. Furthermore, chemical shift calculations based on NMR structures are shown to be capable of acting as a further constraint on structure, by limiting the range of side-chain conformations adopted in structures calculated from NMR data.

Bacterial Proteins↗

A method for the calculation of protein alpha-CH chemical shifts.

The chemical shifts of C(alpha)H protons have been calculated for 9 proteins, based on coordinates taken from high-resolution crystal structures. Chemical shifts were calculated using ring-current shifts, shifts arising from magnetic anisotropies of bonds, and shifts arising from the polarizing effect of polar atoms on the C(alpha)H bond. The parameters used were refined iteratively to give the best fit to (experimental-random coil) shifts over the set of 9 proteins. A further small correction was made to the averaged Gly C(alpha)H shift. The calculated shifts match observed shifts with correlation coefficients varying between 0.45 and 0.86, with a standard deviation of about 0.3 ppm. The differences between calculated and observed shifts have been studied in detail, including an analysis of different crystal structures of the same protein, and indicate that most of the differences can be accounted for by small differences between the structure in solution and in the crystal. Calculations using NMR-derived structures give a poor fit. The calculations reproduce the experimentally observed differences between chemical shifts for C(alpha)H in alpha-helix and beta-sheet. Most of the differentiation in secondary-structure-dependent shifts arises from electric field effects, although magnetic anisotropy also makes a large contribution to the net shift. Applications of the calculations to assignment (including stereospecific assignment) and structure determination are discussed.

Carbon↗

Clinical application of total body retrograde perfusion to operation for aortic dissection.

The use of profound hypothermia and total circulatory arrest in the surgical treatment of aortic dissection has previously been reported. However, the safe period of prolonged circulatory arrest with hypothermia remains controversial. We have developed a technique of hypothermic total body retrograde perfusion to achieve systemic organ protection: cerebral protection by continuous retrograde perfusion through the superior vena cava, myocardial protection by coronary sinus infusion, and abdominal visceral organ perfusion by continuous retrograde perfusion through the inferior vena cava. Our technique yields a relatively bloodless operating field and avoids hypoperfusion of vital organs through a false lumen.

Adolescent↗

Cytochrome P450-mediated prostaglandin omega/omega-1 hydroxylase activities in porcine ciliary body epithelial cells.

The ocular hypotensive effect of topically applied prostaglandins (PGs) is well documented. Although PGs introduced in the posterior chamber accumulate in the anterior tissues (e.g. iris/ciliary complex), little is known about the metabolism of PGs by these tissues. We have recently found that non-pigmented epithelial (NPE) cells and pigmented epithelial (PE) cells are readily separated from porcine ciliary body and cytochrome P450-dependent xenobiotic metabolism is considerably higher in NPE cells than in PE cells. We have therefore investigated in this study the cytochrome P450-mediated PG omega/omega-1 hydroxylase activities of porcine ciliary epithelial cells. The NPE cells show about three times higher activities than do PE cells; the NPE cells, in fact, demonstrate the highest PG omega/omega-1 hydroxylase activities among different ocular tissues. Both omega and omega-1 hydroxylases show broad substrate specificities and hydroxylate PGA1, A2, E1, E2, and lauric acid. The omega/omega-1 hydroxylase activities of NPE and PE, as determined with PGA2 and lauric acid as substrates, are enhanced or induced by treatment of primary cultures of the individual epithelial cells with clofibrate, both activities reaching maximum levels within 48 hr of induction. The induced activities are inhibited almost completely by cycloheximide and actinomycin D. The omega/omega-1 hydroxylase activities of both NPE and PE cells require NADPH and molecular oxygen, are associated with the microsomal fraction, respond to inducers such as clofibrate, and are inhibited by metyrapone and SKF525 A (inhibitors of P450 enzymes). These results support the suggestion that PG omega/omega-1 hydroxylations by NPE and PE are cytochrome P450-mediated reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of local tumor removal and retained oncolysate on lung metastasis.

We reported earlier that oncolysate retained in the excision wound of a local tumor inhibits growth of remote tumor in the rat. We further studied this effect on pulmonary metastasis. C57BL/6 mice were given B16 melanoma F10 cells subcutaneously into the gluteal area (Day 0) and then intravenously on Day 10. On Day 14, mice were divided into four groups. Group 1 received a sham operation and no further treatment. Tumors were excised in the remaining mice. Group 2 received tumor excision alone. Groups 3 and 4 received injections of freeze-lysed tumor cells (TC) and lysate modified (PTC) with a hapten, L-phenylalanine mustard (PhM), respectively, into excision wounds. On Day 24, metastases were assessed by determining metastatic burden. Average diameters of excised tumors in repeated experiments ranged from 8.7 to 10.9 mm. In repeat experiments, pulmonary metastatic burden increased by as much as 52 to 181% in the tumor excised group (Group 2) in comparison with those receiving sham surgery (Group 1). However, metastatic burden was always reduced in Group 3. An even greater reduction was seen in Group 4. To study the possible involvement of macrophages, the production of prostaglandin-E2 (PGE2) and cytotoxicity of macrophages in these animals were examined. It was found that tumor excision enhanced PGE2 production by macrophages and suppressed their cytotoxicity, while TC inoculation prevented both of these changes. An even greater prevention was observed with PTC inoculation. These results indicate an association among macrophage cytotoxicity, PGE2 production of macrophages, and metastasis. In order to clarify the mechanism for these reactions, we did experiments using adherent splenic macrophages from the four groups of animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗