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Biomedical subjects

Y Yabe

Publications and source records attributed to Y Yabe.

At least 55 records · Page 3Linked to original sources

Renal disposition of recombinant human interleukin-11 in the isolated perfused rat kidney.

PURPOSE: To clarify the mechanism of the renal clearance of recombinant human interleukin- 11 (rhIL- 1), we investigated the renal disposition characteristics of rhIL-11 in the perfused rat kidney. METHODS: The disposition characteristics of (111)In-labeled rhIL-11 were analyzed using a single-pass indicator dilution technique and statistical moment analysis in the perfused rat kidney under filtering and nonfiltering conditions. RESULTS: Steady-state distribution volume (Vd) calculated from the venous outflow patterns of rhIL-11 at the doses of 0.3 to 10 microg/kidney was between 0.35 and 0.40 ml/g kidney. However, Vd at the highest dose decreased to a value almost identical to that of bovine serum albumin, suggesting that there is a reversible and saturable interaction between the capillary wall and rhIL-11 molecule. In filtering kidney, a remarkable accumulation of rhIL-11 was observed while its urinary excretion was highly restricted at all doses. In nonfiltering kidney, rhIL-11 showed a decreased but still significant renal uptake. Taken together, the marked renal uptake of rhIL-11 may be explained by both efficient tubular reabsorption and significant uptake from the capillary side. These processes were not saturable within the tested dose range. These characteristics of rhIL-11 are likely based on non-specific electrostatic interaction with the tissues due to its cationic charge in the cytokine. CONCLUSIONS: The renal disposition processes of rhIL-11 were clarified at organ level in a quantitative manner. These findings agree well with previous observations in an in vivo disposition study in mice.

Animals↗

Decreased choline acetyltransferase activity in the murine spinal cord motoneurons under chronic mechanical compression.

The tiptoe-walking Yoshimura (twy) mouse is a model of chronic spinal cord compression caused by ossification of intraspinal ligaments. Choline acetyltransferase (CAT), which is known to be a specific marker of cholinergic neurons, best reflects spinal motoneuron function. Changes in CAT immunoreactivity following chronic spinal cord compression in twy mice were investigated quantitatively in order to elucidate spinal motoneuron functional changes according to the degree and direction of compression. Thirty 24-week-old twy mice were used in this study. They were divided into three groups according to the direction of spinal cord compression (anterior, posterior, and lateral) and the CAT immunoreactivities in whole sections of their upper cervical spinal cords were investigated quantitatively using a fluorescence microphotometry system. The lateral compression group showed histological spinal motoneuron atrophy and loss on the compressed, but not the non-compressed, side. Spinal motoneuron atrophy and loss were observed when the severity of spinal canal stenosis due to the ossified lesion, expressed as the occupation rate, was 30% or more, but the spinal motoneurons appeared normal when it was below 30%. The CAT immunofluorescence intensity of the anterior horn showed a linear negative correlation with the degree of canal stenosis. When the occupation rate was below 20%, the CAT immunofluorescence intensities in the anterior horns of the compression and control groups did not differ significantly. The CAT immunofluorescence intensity of twy mice with occupation rates of 20% or more were significantly lower than that of those with occupation rates below 20%. Furthermore, the CAT immunofluorescence intensity was significantly lower on the compressed than the non-compressed side of the lateral compression group. Thus, our findings indicate that an occupation rate of about 20% may be the critical level for functional changes in the spinal motoneurons.

Animals↗

Effect of dibutyryl cyclic adenosine monophosphate on skeletal muscle reperfusion injury in the rat.

To clarify the action of dibutyryl cyclic adenosine monophosphate (DBcAMP) on reperfused ischemic muscle, experiments were conducted using the hindlimbs of 18 male Lewis rats. At the midportion of the thigh all tissues except for the femoral artery and vein were transected, and a route for continuous intravenous infusion was secured in a contralateral limb vein. After inducing total ischemia by clamping the femoral artery and vein with a vascular clamp for 4 h, the limb was reperfused for 1 h. Blood flow was then compared using the hydrogen gas clearance method in a group in which DBcAMP 10 mg was continuously infused from a vein in the contralateral hindlimb from 1 h prior to the induction of ischemia to 1 h after the completion of ischemia (DBcAMP group), a group in which saline was infused in the same manner (control group), and a group which was subjected to biopsy alone (biopsy group). The percent change in blood flow was significantly higher in the DBcAMP group than in the control group at 15 and 30 min after the release of the clamp. Adenosine triphosphate (ATP), phosphocreatine (PCr), and lipid peroxide (LPO) were measured in tissue samples obtained 1 h after reperfusion. Serum LPO was measured in blood samples collected at the same time. ATP values were higher in the DBcAMP group than in the control group. PCr was significantly higher in the DBcAMP group than in the control group. LPO levels in skeletal muscle tissue did not differ significantly between the DBcAMP and control groups. In contrast, serum LPO levels were significantly lower in the DBcAMP group than the control group. On morphologic analysis the control and DBcAMP groups showed normal vascular endothelial cells and absence of the 'no-reflow' phenomenon. These data confirm that in this reperfusion model the administration of DBcAMP enhances the viability of skeletal muscle cells. Moreover, mediated by an effect on vascular endothelial cells this agent is thought to be of help in mitigating the vascular endothelial cell injury occurring in acute ischemic injury. DBcAMP may be a useful agent in mitigating skeletal muscle ischemia-reperfusion injury.

Adenine Nucleotides↗

A case of favorable dilation of protected left main coronary artery lesion achieved through performance of adjunctive DCA on residual stenosis following use of rotablator.

It is believed that directional coronary atherectomy (DCA) is more suitable than percutaneous transluminal coronary angioplasty for lesions such as severe eccentric lesions, ostial lesions, and branch lesions. However, it remains a fact that lesions that are also highly calcified are often suboptimal, since there may be difficulties such as in insertion of the housing and in sufficient cutting and removal. On the other hand, Rotablator is effective on calcified lesions, but afterward, dilation by balloon angioplasty for residual stenosis becomes necessary in many cases. This is a report of the authors' experience on an interesting case in which favorable dilation of a lesion in the protected left main coronary artery (LMCA) was achieved by using Rotablator after confirmation of a high degree of calcification by means of intravascular ultrasound (IVUS) echocardiograhy, followed by the performance of DCA on the residual stenosis.

Angioplasty, Balloon↗

In vitro and ex vivo anti-human immunodeficiency virus (HIV) activities of a new water-soluble HIV protease inhibitor, R-87366, containing (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid.

In a series of compounds containing (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid (AHPBA), a transitionstate mimetic, R-87366:(2S,3S)-3-[N-(quinoxaline-2-carbonyl)-L-asparaginyl]amino- 2-hydroxy-4-phenylbutanoyl-L-proline tert-butylamide, was found to be a potent human immunodeficiency virus protease inhibitor (Ki value was 11 nM) and anti-HIV agent (IC90 value was 0.5 microM for HIV-1IIIB acutely infected cells) with moderate water-solubility (4.2 mg/ml at 25 degrees C). The compound was also active in chronically infected Molt-4/HIV-1IIIB cells, and inhibited the proteolytic processing of p55 into p17, suggesting that its anti-HIV activity was derived from HIV protease inhibition. The compound showed more potent activity (IC90 value was 0.03-0.25 microM) against clinical isolates of HIV in 5 out of 6 patients examined with varying clinical status in an ex vivo assay. One isolate, however, from the sixth patient, was less sensitive to R-87366 (IC90 value was 0.5 microM). In experiments with this strain, R-87366 showed comparatively low efficacy in acutely infected peripheral blood mononuclear cell (PBMC). This result suggests that the diversity of sensitivity shown in the ex vivo assay could be caused by the viral property itself. As a result of the determination of nucleic acid sequences in the clinical isolates, some amino acids were found to be substituted in the protease region, in contrast to the HIV-1 clade B consensus sequence, and some of them have been reported to contribute to the susceptibility of HIV protease inhibitors.

Amino Acid Sequence↗

Magnetic resonance myelography in brachial plexus injury.

We used magnetic resonance (MR) myelography in ten patients with injuries to the brachial plexus and compared the findings with those obtained by conventional myelography and postmyelographic CT (CTM). In the presence of complete nerve-root avulsion (seven cases), a post-traumatic meningocele was detected by MR myelography. In injuries to the upper roots (three cases) MR myelography showed abnormal findings with a high signal intensity in the nerve root, obliteration of the damaged nerve root, or enlargement and obliteration of the root sleeve. No pseudomeningoceles were detected in these upper-root injuries by MR myelography and CTM. The overall accuracy of detection of damaged nerve roots or root sleeves was better with MR myelography than with conventional myelography and was similar to that of CTM. MR myelography is non-invasive, relatively quick, requires no contrast medium, provides imaging in multiple projections, and is comparable in diagnostic ability to the more invasive, time-consuming techniques of conventional myelography and CTM.

Adolescent↗

A perfluorochemical prevents ischemia-reperfusion injury of muscle.

This investigation evaluated the effect of oxygenated perfluorochemical (PFC) perfusion on the viability of ischemic skeletal muscle compared to hypothermic preservation. Twenty-five hindlimbs of 13 white rabbits were divided into five groups: a PFC group (7 hr of ischemia with 6 hr of PFC perfusion), a PFC/ reperfusion group (8 hr of ischemia with 6 hr of PFC perfusion and 1 hr reperfusion), a hypothermia group (7 hr of ischemia with 6 hr of 4 degrees C cold preservation), a hypothermia/reperfusion group (8 hr of ischemia with 6 hr of 4 degrees C cold preservation and 1 hr of reperfusion), and a control group. The levels of adenine nucleotides, creatine phosphate, hypoxanthine, xanthine, and lipid peroxide were determined in each group. In the PFC and PFC/reperfusion groups, the ATP level remained at 90% of that in the control group. The hypoxanthine level in the hypothermia/reperfusion group was decreased to 70% of that in the hypothermia group and the xanthine level was increased to 130%. In the PFC and PFC/reperfusion groups, hypoxanthine and xanthine levels were much lower and were similar to those in the control group. Lipid peroxide levels were also lower in the PFC and PFC/reperfusion groups than in the hypothermia/reperfusion group. Electron microscopy showed that endothelial cells from the PFC/reperfusion groups were not swollen. These results suggest that PFC perfusion is superior to hypothermia in inhibiting the generation of free radicals and in preventing ischemia-reperfusion injury of skeletal muscle.

Adenine Nucleotides↗

Changes in choline acetyltransferase activity and distribution following incomplete cervical spinal cord injury in the rat.

Incomplete cervical spinal cord injuries were produced in rats by placing 10 g or 20 g weight on exposed dura at the C6 level for 5 min (Mild or Moderate injury). These two degrees of the injury resulted in initial motor functional deficits, followed by recoveries. In this study, changes in choline acetyltransferase activity and distribution following the incomplete cervical cord injuries were investigated using radioenzyme assay, and fluorescence microphotometry. We demonstrated that mild injury led to a transient decrease of choline acetyltransferase activity in the compressed spinal cord segment, but showed almost no histologic change at two days after injury. Although a low level of choline acetyltransferase immunofluorescence was found in the ventrolateral anterior horn at two days after injury, it recovered completely by one week after injury. These findings suggest that there was a strong correlation between the transient motor functional deficit and the decrease in choline acetyltransferase activity following mild injury. Moderate injury resulted in persistent low level of choline acetyltransferase activity in the compressed spinal cord segment accompanied by a striking loss of gray matter. On the other hand, at seven, 14 and 28 days after injury, over-expression of choline acetyltransferase activity was found in the neighboring spinal cord segments located both rostral and caudal to the injury, which showed no histologic change. In addition, excessively high levels of choline acetyltransferase immunofluorescence were found in the ventrolateral anterior horn of these segments. A strong correlation was found between the motor functional recovery and the late, excessive high levels of choline acetyltransferase activity in the neighboring regions. These results suggest that cholinergic neurons, especially spinal motor neurons may play an important role in the motor functional recovery following incomplete cervical spinal cord injury.

Animals↗

Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA--II. Modification of pyrrolidine ring at P1' proline.

Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a Cl atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with five- or six-membered fused aromatic heterocycle carbonyl groups produced more potent inhibitors. 7-Methoxybenzofuran-2-carbonyl derivative (44) was the best of these and showed Ki = 4.5 nM against HIV PR and IC90S 0.58 microM and 0.06 microM in chronic and acute infections, respectively. These results suggest that the combination of the 4(S)-CI atom and fused bicyclic heterocycles may be effective in improving their cellular penetration.

Cells, Cultured↗

Functional anatomy of the triangular fibrocartilage complex.

The functional anatomy of the triangular fibrocartilage complex (TFCC) was investigated in 20 fresh cadavers. Dynamic changes in the TFCC during rotation were also examined from both the proximal and distal aspects. In our analysis, the TFCC was separated into three components. The distal component was stable, functioning like a hammock to suspend the ulnar carpus. The proximal component was the fan-shaped triangular ligament, the true radioulnar ligament. This was found to originate from the fovea of the ulna in a vertical fashion and was easily twisted during rotation. The third component, the ulnar collateral ligament, also twisted during rotation. When analysed by coronal section, the internal portion of the TFCC was found to be loose, and probably serves as a cushion to absorb local deformities in the TFCC during rotation.

Adolescent↗

Estimating myocardial damage and the need for surgery in patients with valvular heart disease by Tl-201 SPECT.

Left ventricular myocardial disorders due to volume overload were investigated by Tl-201 myocardial SPECT (Tl-201 SPECT) in patients with aortic or mitral regurgitation, and its utility for timing cardiac valve replacement was studied. There were significant correlations between Tl-201 scores and electrocardiographic changes and the New York Heart Association classification. There also were favorable correlations between Tl-201 scores and the left ventricular end-diastolic dimension and between Tl-201 scores and left ventricular ejection fraction, and a close relationship between the presence of a left ventricular myocardial disorder and left ventricular diameter. These results suggest that myocardial perfusion abnormalities and left ventricular myocardial disorders may accompany left ventricular dilatation owing to volume overload. After valve replacement, left ventricular end-diastolic dimension normalized, and Tl-201 scores improved slightly, suggesting normalization of myocardial perfusion. When moderate or more severe Tl-201 defects are present on Tl-201 SPECT images, in addition to inverted Tl-201 waves on the electrocardiogram or a left ventricular end-diastolic dimension of 65 mm or more, cardiac valve replacement should be considered.

Aortic Valve Insufficiency↗

Percutaneous transluminal coronary angioplasty for culprit lesions in patients with post myocardial infarction angina based on dextrocardia and anomalous coronary arteries. Case reports and methods.

Four cases of successful coronary angioplasty for anomalous coronary arteries, including dextrocardia associated with three-vessel disease, single left coronary artery with proximal left anterior descending lesion, anomalous right coronary artery (RCA) from adjacent left coronary sinus of Valsalva associated with proximal RCA lesion, and anomalous left circumflex angulated lesion bifurcated from the RCA, were encountered. Four cases with 8 target lesions who had a mean age of 63.5 +/- 11.5 years old are presented. All the targets lesions were completely dilated through balloon angioplasty, including use of a newly developed support device for cases with large jeopardized myocardium. The factors for complete revascularization were appropriate selection of catheters and originality and ingenuity of procedural technique based on the anatomic characteristics.

Aged↗

Efficacy and issues of emergent percutaneous transluminal coronary angioplasty. Comparison of clinical results in younger and elderly patients.

The authors investigated the efficacy and prognosis of emergency percutaneous transluminal coronary angioplasty (PTCA) in elderly patients. A study was conducted on the early and late prognosis of the study group composed of 66 younger patients < sixty-five years in Group A and 46 elderly patients > or = seventy years in Group B who underwent reperfusion therapy, including PTCA, for acute myocardial infarction (AMI). No difference was seen in the initial success rate of 82% for Group A and 85% for Group B, or in the vessel patency in the predischarge coronary arteriogram (CAG) with 84% for Group A and 87% for Group B. However, in-hospital mortality was 3% for Group A and 11% for Group B. The patient restenosis rate in the 4.2 months follow-up CAG was 28% for Group A and 50% for Group B. The lesion restenosis rate was 30% for Group A and 53% for Group B (P < 0.05), and the late period mortality rate was 3% for Group A and 11% for Group B. Although there was no difference in the initial success rate of reperfusion through PTCA for AMI in the elderly as compared with the younger patient group, poorer results were seen in the restenosis rate and mortality rate.

Age Factors↗

[A study of the efficacy of thrombolytic therapy for acute myocardial infarction in elderly patients].

We compared the short and long term outcome between an elderly group (E; aged 70 year more, 17 cases) and a younger group (Y; less than 70 years, 95 cases). Reperfusion rates were similar in both groups (E; 70.6% vs Y; 67.3%). Reocclusion rates at predischarge CAG were similar in both groups (E; 70.6% vs Y; 67.3%). Reocclusion rates at predischarge CAG were similar in both groups (E; 7.2% vs Y; 6.8%). Hospital cardiac deaths in E were higher than Y (E; 5.9% vs Y; 4.2%). Intestinal bleeding in E was more frequent than in Y (E; 5.9% vs Y; 3.2%). We concluded that thrombolytic therapy for acute myocardial infarction in elderly patients was useful, however bleeding complication in elderly patients were higher than in younger patients.

Aged↗

Human papillomavirus type 16 DNA detected by the polymerase chain reaction in non-cancer tissues of the head and neck.

Cancer-free tissues from various anatomical subsites in the head and neck were examined by the polymerase chain reaction (PCR) for the incidence of human papillomavirus (HPV) types 16 and 18. We detected HPV-16 DNA in 9 of 103 samples (8.7%), including specimens from the paranasal sinuses, tonsil, hypopharynx and larynx. However, no HPV-16/18 DNA was detected by Southern hybridization in these 9 samples. The significance of the presence of HPV-16 DNA in non-cancer tissues is still unknown, but PCR detection only of high-risk HPV DNA in head and neck cancer should be evaluated cautiously because of its ubiquity in this region.

Adolescent↗