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Biomedical subjects

H Yuasa

Publications and source records attributed to H Yuasa.

At least 199 records · Page 11Linked to original sources

Laser measurement of myocardial blood flow.

A He-Ne laser flowmeter (wavelength: 632.8 nm, power: 2 mW) has already been used to measure blood flow in skin, muscle, and mucosa. However, the application of this flowmeter for the beating heart has been left undeveloped due to its difficulty. For the purpose of establishment of the laser measurement of myocardial blood flow, we redesigned a flow probe to be small and light and used a connecting paste to support the subepicardial flow probe. After resolving many obstacles, the noninvasive and real-time blood flow measurement of the beating heart was made possible. The flow volume in subendocardial myocardium was greater than the volume in subepicardial myocardium, and the average ratio of subendocardial flow to subepicardial flow was 1.62 +/- 0.21.

Animals↗

Hemostatic alterations caused by ventricular assist devices for postcardiotomy heart failure.

The hemostatic alterations in two adult patients who were supported by left ventricular assist devices (LVADs) because of postcardiotomy heart failure were evaluated. In both patients, fibrinopeptide A and thrombin-antithrombin III complex increased markedly during the first several days, and thereafter decreased moderately but remained above normal over the entire procedure. Furthermore, fibrinopeptide B beta 15-42 and alpha 2 plasmin inhibitor-plasmin complex were also markedly increased over the entire course of LVAD treatment. These data show that the LVAD system strongly activates both the coagulation and the fibrinolytic system, even when thromboembolic or bleeding complications are not clinically evident. Furthermore, the decrease in physiological coagulation inhibitors, especially protein C, indicates that these factors are activated and consumed during LVAD treatment. Because protein C is important in regulating the coagulation cascade during LVAD treatment, exhaustion of this system might result in thromboembolic complications during LVAD treatment.

Aged↗

Incidence of aneurysms in Takayasu's arteritis.

The angiographic findings of Takayasu's arteritis in a series of 113 patients were reviewed. Predominant findings were stenotic or occlusive changes, but fusiform or saccular aneurysms were also found in 36 patients (31.9%) in the various sites of aorta and its major branches. Multiple aneurysms were found in 15 patients. The most common site of aneurysms was the ascending aorta (16 patients); in 7 of the patients these were complicated by aortic regurgitation. Aneurysms developed in the aortic arch in 3 patients, in the descending aorta in 11, in the abdominal aorta in 7, and in the major branches of the aortic arch in 9 patients. In 2 patients, follow-up angiograms showed enlargement of the aneurysms, and rupture of the aneurysm occurred in 1 patient. Aneurysms were found even in young patients. A fifteen-year-old female showed a huge aneurysm in the ascending aorta as the initial manifestation of this disease. Thickening of the walls of aneurysms was common and characteristic. This study revealed the moderately high incidence of aneurysms of various sites of arteries in patients with Takayasu's arteritis. The authors conclude that aneurysm, as well as occlusive changes, can be a primary lesion.

Adolescent↗

[Surgical repair of ischemic mitral regurgitation].

We studied surgical results of 14 cases of ischemic mitral regurgitation. There was no surgical death in 10 cases with left ventricular aneurysm, and their clinical symptoms improved except 3 with the combined operation of left ventricular aneurysmectomy, mitral annuloplasty and bypass grafting. The range of the abnormal contracting segment significantly decreased after surgery except in 3 cases in whom clinical status was not improved. Three of 4 cases which underwent bypass grafting and mitral annulo-valvuloplasty survived, but one of them died of graft-versus-host disease. In the three survived cases, severe mitral regurgitation disappeared. We have concluded as follows: In cases of left ventricular aneurysm, a sufficient aneurysmal resection is very important to control the mitral regurgitation, and the additional procedures of mitral annuloplasty and bypass grafting are essential. The mitral valve replacement is recommended in case of the complete disruption of the papillary muscle. Mitral valvuloplasty combined with annuloplasty is suitable to control the regurgitation in the regional mitral prolapse due to the torn chordae.

Adult↗

Thermo-responsive hydrogels based on acryloyl-L-proline methyl ester and their use as long-acting testosterone delivery systems.

New thermo-responsive hydrogels were synthesized by copolymerizing acryloyl-L-proline methyl ester (A-ProOMe) with minor amounts of 2-hydroxypropyl methacrylate (HPMA) or polyethylene glycol 600 dimethacrylate (14G), using gamma-rays from a 60Co source. In water, extensive swelling of the hydrogels occurred at 10 degrees C, but there was marked deswelling as the temperature was raised to 37 degrees C. The poly(A-ProOMe-co-HPMA) hydrogel was characterized by an initial rapid shrinkage at the surface in the deswollen state; this shrinkage arose because of the formation of a rigid membrane barrier devoid of micropores. The system is therefore 'surface regulated'. In contrast, no such a barrier formed in the deswollen poly(A-ProOMe-co-14G) hydrogel. The whole matrix shrunk without the disappearance of micropores, and it is therefore a 'matrix pumping' system. Testosterone was incorporated into both these types of hydrogels, and the drug-loaded hydrogels were implanted subcutaneously into the backs of castrated rats. The daily dose of testosterone released in vivo from the poly(A-ProOMe-co-HPMA) hydrogel was constant at approximately 30 micrograms/day throughout an experimental period of 54 weeks. In contrast, drug release from the poly(A-ProOME-co-14G) hydrogel reached a maximum after one week and then decreased linearly with time down to the 7th week, when it was undetectable. These conclusions were supported by the changes in weight of the ventral prostates and right-side seminal vesicles of the rats, which were restored to normal when delivery of the testosterone was sustained.

Animals↗

Homophilic binding of mouse monoclonal antibodies against GD3 ganglioside.

R24, a mouse IgG3 mAb against GD3 ganglioside, was shown to bind to itself in a homophilic manner. This was demonstrated by augmented binding of 125I-labeled R24 to the cell surface of GD3+ cells by unlabeled R24 and by direct binding of biotinylated R24 to R24 adsorbed on solid phase. Although homophilic binding was evident when R24 was bound to solid phase, R24-R24 aggregates could not be detected in solution under otherwise identical conditions. R24 bound to four other mAb (two IgG3, one IgG2a, one IgM) directed against GD3 but did not bind to a panel of 21 other mAb including other IgG3 mAb and mAb directed against non-GD3 ganglioside. Evidence implicating the GD3-binding site of R24 in homophilic binding included the following observations: 1) F(ab')2 fragments of R24 could bind to R24, 2) an antiidiotypic mAb against the GD3-binding site of R24 inhibited R24 homophilic binding, 3) an IgM anti-GD3 mAb also demonstrated homophilic binding to R24, and 4) homophilic binding was a function of immunoreactivity and avidity for GD3. R24 variants with 40-fold lower avidity for GD3 demonstrated a similar decrease in homophilic binding. Inasmuch as R24 bound to R24 F(ab')2 fragments and specifically to anti-GD3 mAb, it appeared that the target for homophilic binding was an epitope within the V region of anti-GD3 mAb. It is likely that homophilic interactions result in increased affinity of R24 for GD3 through increased effective valency of antibody-Ag complexes.

Animals↗

The spontaneously epileptic rat (SER), a zitter*tremor double mutant rat: histopathological findings in the central nervous system.

The spontaneously epileptic rat (SER), a mutant homozygous for both zitter and tremor genes, exhibits absence-like seizures and tonic convulsions without external stimulation from 7 to 8 weeks of age. Histopathological studies of the central nervous system revealed the following abnormalities. The 35-day-old SERs which exhibit body tremor, and which have never shown seizures, had marked vacuolation and hypomyelination in the brainstem and cerebellum. The vacuoles were produced by splitting of the myelin sheaths and swelling of the dendrites and were related to primary swelling of the astrocytes. The 2- to 3-month-old SERs with staggering gait and seizures showed focal axonal swelling ('torpedo') and advanced vacuolation in the granular cell layer of the cerebellum in addition to the abnormalities observed at 35 days of age. Degenerative neurons and spheroidal bodies were observed in the substantia nigra and ventral tegmental nucleus. These brain areas are known to be related to tonic convulsions in the several experimental models. The SER is believed to be a useful tool for the investigation of the relationship between the structure and function of the central nervous system in epilepsy. It is probable that the more severe changes in the cerebellum are responsible for the staggering gait.

Animals↗

Sequential polydepsipeptides as biodegradable carriers for drug delivery systems.

Sequential polydepsipeptides containing both peptide and ester bonds, poly[(L-alanyl)n-gamma-ethyl L-glutamyl-L-lactyl] (n = 0, 1, 2, and 3) (poly[(Ala)n-Glu(OEt)-Lac]), were prepared for application as biodegradable carriers for drug delivery systems. The in vivo degradation of these polymers was evaluated by subcutaneous implantation in the backs of male rats, and was strongly influenced by the number (n) of Ala units in poly[(Ala)n-Glu(OEt)-Lac]. The resulting poly(Ala-Ala-Glu(OEt)-Lac) gave the highest degradability, in which 100% degradation was observed 24 weeks from the start of implantation. A luteinizing-hormone-releasing hormone agonist des-Gly10-[D-Leu6]-LH-RH ethylamide (LH-RH agonist), was incorporated into a sequential poly(Ala-Ala-Glu(OEt)-Lac) carrier by the melt-pressing technique, which gave fine cylindrical polymer formulations with different structures of drug dispersion, e.g., blend-type and sandwich-type formulations. The rate of in vivo release of LH-RH agonist from a blend-type formulation showed a linear decrease with time until its release was finished after 6 weeks' implantation. In contrast, in a sandwich-type formulation, the in vivo release rate was apparently maintained constant over a period of 16 weeks (24 +/- 14 micrograms/day).

Amino Acid Sequence↗

In vivo characteristics of low molecular weight copolymers composed of L-lactic acid and various DL-hydroxy acids as biodegradable carriers for drug delivery systems.

Low molecular weight and amorphous copolyesters composed of 70 mol% L-lactic acid and 30 mol% DL-hydroxy acids such as DL-lactic acid, DL-alpha-hydroxy-n-butyric acid, DL-alpha-hydroxyisovaleric acid and DL-alpha-hydroxyisocaproic acid were synthesized by direct copolycondensation in the absence of catalysts, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. For this purpose, the copolyester was moulded into a small cylindrical specimen under melt-pressing technique and implanted subcutaneously in the back of male adult rats. The in vivo degradation pattern can be subdivided into three types: the formations of parabolic type (L-LA/DL-HBA copolymer), linear type (L-LA/DL-LA copolymer) and S type (L-LA/DL-HIVA and L-LA/DL-HICA copolymers). A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide monoacetate (LH-RH agonist), was incorporated into the small cylinders of copolyester formulations, of which the strongest pharmacological influence was observed in a copoly(L-LA/DL-HICA) formulation system, resulting in the maintenance of effective pharmacological influence throughout an experimental period of 15 wk, at which the in vivo release rate of LH-RH agonist was held constant at approximately 45 micrograms/d.

Animals↗

Macromolecule-macromolecule interaction in drug distribution: effect of alpha-globulin concentration on the hepatic uptake of fractionated 3H-heparin by perfused rat liver.

The effect of alpha-globulin, the dominant binding protein for fractionated 3H-heparin, on the hepatic uptake of 3H-heparin was studied by liver perfusion experiments in rats. Fractionated 3H-heparin concentration in the recirculated perfusate decline one-exponentially with time for each of six initial concentration levels of alpha-globulin. The hepatic uptake clearance of fractionated 3H-heparin was 0.154 ml/min/g liver in the absence of alpha-globulin, and it decreased with increasing alpha-globulin concentrations. This result indicates that the hepatic uptake rate of alpha-globulin-bound fractionated 3H-heparin is lower than that of unbound fractionated 3H-heparin. On the other hand, it was indicated that almost all fractionated 3H-heparin binds to alpha-globulin at 8 mg/ml of alpha-globulin in in vitro study. However, the hepatic uptake clearance of the heparin at the concentration was of a certain value that could not be ignored. It was suggested that alpha-globulin-bound fractionated 3H-heparin also contributed to the hepatic uptake of fractionated 3H-heparin. Therefore, a protein-mediated transport system, which has been reported for some low molecular weight drugs, may also exist in the hepatic uptake of such a high molecular weight compound as fractionated 3H-heparin.

Alpha-Globulins↗

Inter-organ relation between salivary gland and kidney in lithium excretion. III. Enhanced salivary and systemic clearance of Li+ by oral administration of NaCl in dogs.

Effects of oral administration of NaCl on salivary and systemic clearance of Li+ were investigated following bolus intravenous administration of LiCl in male beagle dogs. Fifty ml of NaCl solution (100 meq/l) was administered orally 7 times at 1 h intervals. Gustatory stimulation of salivation was continued for 390 min using citric acid solution. Saliva was collected by means of permanent fistulae for parotid and mandibular-sublingual glands. Salivary clearance of Li+ was markedly increased by continuous stimulation of salivation, and was enhanced further after oral administration of NaCl solution. Renal clearance of Li+ showed a decreasing tendency under continuous salivation compared with the condition without gustatory stimulation; however, this decreasing tendency disappeared after oral administration of NaCl solution. Consequently, systemic clearance of Li+ was increased due to the contribution of increased salivary clearance. Enhancement of salivary Li+ clearance after administration of NaCl suggests the salivary excretion mechanism of Li+ may include a reabsorption process, like its renal excretion. Administration of NaCl solution had similar effects on salivary and systemic clearances of K+ to those on Li+ clearances, and a significant correlation was observed between Li+ and K+ clearances of both salivary gland and kidney.

Animals↗

Studies on internal structure of tablets. III. Manufacturing of tablets containing microcapsules.

The aim of this study was to establish the best manufacturing conditions for preparation by the direct compression method of tablets which contain microcapsules having a minimal destruction rate of the coating wall, show the same dissolution pattern as microcapsules, and have enough mechanical strength for practical use, and to elucidate the internal structure of the tablets under the best manufacturing conditions. Degree of destruction of the microcapsule wall was evaluated by the dissolution rate of the medicine in the microcapsules. To learn the mechanical strength of tablets, the crushing strength and friability were measured; their internal structure was analyzed by the porosity and pore size distribution. The best manufacturing conditions for the tablets were thus determined, and it was clarified by analysis of the internal structure that these conditions are markedly affected by the flowability of prescribed powders and the packing state at compression.

Capsules↗

Familial pituitary adenoma--report of four cases from two unrelated families.

The authors report four cases of familial pituitary adenomas from two unrelated families. No clinical or biochemical evidence of multiple endocrine neoplasia, type I (MEN-I) was demonstrated. Detailed study of the family trees disclosed no other family members affected by MEN-I. Familial occurrence of pituitary adenomas unassociated with MEN-I is rare.

Adenoma↗

[Evaluation of aortocoronary bypass operation using a He-Ne laser flowmeter--comparison between internal mammary artery grafts and saphenous vein grafts].

It was very difficult to measure myocardial blood flow in clinical cases. Recently, a He-Ne laser doppler flowmeter was developed, and we made it possible to measure the pre-and post-operative myocardial blood flow in cases of coronary artery bypass grafting (CABG). We applied a laser flowmeter to 30 cases of bypass grafting to the left anterior descending coronary artery (18 cases with IMAG and 12 cases with SVG). The preoperative myocardial blood flow at the right ventricular anterior wall was 77 +/- 15 ml/min/100 gr, and the postoperative flow at the same point was 81 +/- 12 ml/min/100 gr. There was no significant change between the pre-operative value and the postoperative one. Myocardial blood flow at the left ventricular anterior wall in SVG group significantly increased from the preoperative value of 58 +/- 11 ml/min/100 gr to the postoperative value of 86 +/- 9 ml/min/100 gr (p less than 0.001). In IMAG group, myocardial blood flow at the left ventricular anterior wall similarly increased from 73 +/- 14 ml/min/100 gr to 83 +/- 15 ml/min/100 gr (p less than 0.01). The postoperative value of IMAG group was almost equal to the value of SVG group. The increased rate of myocardial blood flow at the left ventricular anterior wall was 52 +/- 32% in SVG group and 18 +/- 12% in IMAG group. These rates were obviously distinguished from the increased rate at the right ventricular anterior wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗