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Biomedical subjects

T Yamaguchi

Publications and source records attributed to T Yamaguchi.

At least 577 records · Page 32Linked to original sources

Amino-terminal fragment (1-34) of parathyroid hormone-related protein inhibits migration and proliferation of cultured vascular smooth muscle cells.

We investigated the effects of amino-terminal fragment (1-34) of parathyroid hormone-related protein [PTHrP-(1-34)] on the migration and proliferation of vascular smooth muscle cells (VSMCs). Cultured VSMCs (5-9th passage) obtained from the aortas of male Wistar rats were used in this study. Migration of VSMCs was assessed using a modified Boyden's chamber. Proliferation of VSMCs was evaluated by measuring [3H]thymidine incorporation and counting cell numbers. PTHrP-(1-34) inhibited 10% fetal bovine serum (FBS)-induced increase in migration of VSMCs (61% of control at 1 micromol/l) in a concentration-dependent manner. PTHrP-(1-34) also inhibited 5% FBS-induced increase in [3H]thymidine incorporation (37% of control at 1 micromol/l) and cell number of VSMCs (33% of control at 1 micromol/l) in a concentration-dependent manner. Parathyroid hormone (PTH)-(1-34) inhibited the migration and DNA synthesis of VSMCs to a similar extent. PTHrP-(7-34), a PTH/PTHrP receptor antagonist, significantly inhibited these effects of PTHrP and PTH. PTHrP-(1-34) also inhibited platelet-derived growth factor-BB (5 ng/ml)-induced migration and DNA synthesis of VSMCs. These findings suggest that PTHrP-(1-34) inhibits the migration and proliferation of VSMCs through PTH/PTHrP receptors.

Animals↗

High prebeta1-HDL levels in hypercholesterolemia are maintained by probucol but reduced by a low-cholesterol diet.

Previous study has shown that prebeta1-HDL levels increase in hypercholesterolemia, or high cholesteryl ester transfer protein (CETP) activity. To determine how prebeta1-HDL levels change after treatment with probucol or by following a low-cholesterol diet, we randomly assigned 24 hypercholesterolemic patients to either the probucol (P), or low-cholesterol diet group (D), and measured prebeta1-HDL levels before and after treatments using native two-dimensional gel electrophoresis. We also examined 12 subjects with normolipidemia (N). At baseline, prebeta1-HDL levels were higher in P (P < 0.05) and D (P < 0.05) than in N (9.2 +/- 4.3, 10.4 +/- 5.5, and 5.9 +/- 2.3 mg/dl apo A-I). After a 4-week treatment, prebeta1-HDL levels were still high in P (10.5 +/- 4.2 mg/dl apo A-I, N.S.), but reduced in D (7.7 +/- 3.0 mg/dl apo A-I, P < 0.001). Delta prebeta1-HDL (Y) was positively correlated with deltaCETP mass (X) in P (y = 7.83x - 1.93; r = 0.584, P < 0.05). In summary, high prebeta1-HDL levels in hypercholesterolemia are maintained by probucol but reduced by a low-cholesterol diet. These findings suggest that prebeta1-HDL levels may be regulated by cholesterol and CETP levels.

Aged↗

Prognosis following acute myocardial infarction in patients with ECG evidence of left ventricular hypertrophy prior to infarction.

This study was designed to determine the relationship between prognosis after myocardial infarction (MI) and left ventricular hypertrophy (LVH). Left ventricular hypertrophy diagnosed by electrocardiography according to the criteria of Sokolow and Lyon was noted in 57 of 223 patients (25.6%) on the pre-MI electrocardiogram (ECG), in 11.2% on an early post-MI ECG, and in 11.3% on the discharge ECG. In-hospital and 1-year postdischarge mortalities were significantly greater in patients with LVH noted on pre-MI ECG than in patients without prior LVH. There was no relationship between the presence of LVH on early post-MI ECGs and in-hospital or postdischarge 1-year mortality. Multivariate analysis revealed that evidence of LVH on a pre-MI ECG and acute congestive heart failure were independent predictors of cardiac death within 1 year of MI in patients over 70 years old. It is concluded that in patients over 70 years of age, the presence of LVH on a pre-MI ECG is a reliable predictor of post-MI prognosis.

Cause of Death↗

Neuroprotective effect of YM-39558 in focal cerebral ischemia in cats.

We studied the effect of YM-39558, orotic acid ethylester, in a focal cerebral ischemia model in anesthetized cats. YM-39558 has good permeability across the blood brain barrier, and in the brain is hydrolyzed to orotic acid, the main active substance. Cats were subjected to permanent occlusion of the middle cerebral artery (MCA) for 6 h, then killed and examined histologically. Treatment with YM-39558 (intravenous infusion of 11.8 mg (10 mg as orotic acid)/6 ml per kg per h) starting 15 min after MCA occlusion markedly reduced the volume of ischemic damage (from 2450 +/- 82 mm3 of the cerebral hemisphere in the saline-treated cats to 1644 +/- 123 mm3 in the YM-39558-treated cats, P < 0.01). In contrast, YM-39558 (2.26 and 1.18 mg/0.8 ml per kg per h) showed no significant protective effect on ischemic damage. No significant differences were observed between saline- and YM-39558-treated cats concerning physiological variables including brain temperature. This evidence for the neuroprotective efficacy of YM-39558 in gyrencephalic species suggests its therapeutic potential in the treatment of stroke in humans.

Animals↗

Neurochemical and behavioral characterization of potential antidepressant properties of indeloxazine hydrochloride.

The potential antidepressant properties of indeloxazine hydrochloride were examined in vitro and in vivo. Indeloxazine showed preferential affinity for both [3H] citalopram (Ki: 22.1 nM) and [3H]nisoxetine binding sites (Ki: 18.9 nM) in membranes of the rat cerebral cortex. In microdialysis studies, intraperitoneal injection of indeloxazine (3 and 10 mg/kg) dose-dependently increased the extracellular level of both serotonin and norepinephrine in rat frontal cortex of freely moving rats. Amitriptyline was almost equivalent to indeloxazine in these two assays with the exception of a much weaker effect on extracellular serotonin levels. Spontaneous [3H]serotonin release from rat cortical synaptosomes was significantly enhanced by indeloxazine (10-1000 nM). In behavioral studies, indeloxazine increased the number of wheel rotations in forced swimming tests in both ICR mice (50 mg/kg, p.o.) and SAMP8//YAN, a substrain of senescence-accelerated mouse (20 and 30 mg/kg, p.o.). Indeloxazine (3-10 mg/kg p.o.) also inhibited the incidence of muricide in raphe-lesioned rats. These results suggest that indeloxazine is an inhibitor of serotonin and norepinephrine uptake and has potential antidepressant properties. In addition, the drug-induced enhancement of serotonin release may contribute to its potent effects on the serotonergic system in vivo.

Amitriptyline↗

Genomic heterogeneity maps to tandem repeat sequences in the herpes simplex virus type 2 UL region.

Two Bam HI Y and W fragments in the unique long sequence (UL) of the herpes simplex virus type 2 (HSV-2) were found to be heterogeneous in size among clones derived from a single strain as well as from epidemiologically unrelated isolates. More detailed restriction maps of these BamHI fragments were constructed and the heterogeneous subfragments were defined, cloned, and sequenced in order to investigate the mechanism causing the size difference. The subfragment of BamHI Y contained a tandem repeat sequence consisting of different numbers of 15 bp, 5'AGGGGCGGCTGGGGC3' as one unit among three isolates, and the subfragment of BamHI W contained the other tandem repeat sequence, 9 bp, 5'CCTCCCGCC3'. In the UL of the HSV-2 strain, these tandem repeat sequences were conserved and each repeat number appeared to be highly variable through viral genome replication. These results showed that the fragment length polymorphisms in these regions were attributable to the variation of unit numbers of the tandem repeat sequences.

Base Sequence↗

Oblique alignment of stress fibers in cells reduces the mechanical stress in cyclically deforming fields.

The stress fiber (bundles of actin filaments) is one of the most prominent cytoskeletal components that contributes to the maintenance of cell architecture. It has generally been believed that upon cyclic stretching, both cells and their stress fibers become perpendicularly aligned to the direction of stretching. However, using our newly developed stretching device, we have recently found the contrary evidence that stress fibers in endothelial cells rapidly become rearranged at a specific oblique angle relative to the direction of stretching [Takemasa, T., K. Sugimoto, K. Yamashita: Exp. Cell Res. 230, 407-410 (1997)]. In light of this finding, we attempted to establish the explanation for such a phenomenon. First, we investigated the effects of possible modulators on the angle of the stress fibers; those were, modification of the stretching program, dependency of extracellular matrix types, and their reproducibility in other cell species. However, it seemed that the orientation was solely depending on the stretching amplitude applied. Next, we analyzed alterations in stress fiber length during loading tests using two kinds of deforming experiment systems. It was thus revealed that stress fibers aligned at a particular angle so as to minimize their length alterations in cyclic deforming fields. Rearrangement of the stress fibers at this angle probably occurs as a result of avoiding compressive stress and may be interpreted as a way of reducing the mechanical stress to which they are subjected during the deformation. This hypothesis well explains the reason not only for the survival of the stress fibers at a particular oblique angle, but also for the reduced numbers of stress fibers found at the other angles on cyclic deforming fields.

Actins↗

Characterization of cyclothiazide-enhanced kainate excitotoxicity in rat hippocampal cultures.

Cyclothiazide has been shown to block desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-preferring receptors and to enhance quisqualate-, AMPA- and kainate-induced neurotoxicity. The pharmacology behind this cyclothiazide-enhanced kainate-induced excitotoxicity was characterized in embryonic rat hippocampal cell cultures. Treatment of cell cultures with a combination of cyclothiazide and kainate for 24 h resulted in excessive neuronal death as measured by the release of lactate dehydrogenase into the culture media. Cyclothiazide produced a leftward shift of the kainate dose-response curve and enhanced the maximum response of kainate excitotoxicity. AMPA-preferring receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline(NBQX) and 1-(4-amino-phenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) blocked cyclothiazide-enhanced kainate toxicity completely, and cyclothiazide increased the IC50S for NBQX and GYKI 52466 against kainate toxicity. The N-methyl-D-aspartate (NMDA) antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK801) also blocked cyclothiazide-enhanced kainate toxicity, but only partially. Cyclothiazide also increased the IC50 for MK801 against kainate toxicity. These data suggest that cyclothiazide enhances both AMPA-preferring receptor- and NMDA receptor-mediated toxicity in kainate-induced toxicity in embryonic rat hippocampal cultures.

Animals↗

Oscillating thromboemboli within the extracranial internal carotid artery demonstrated by ultrasonography in patients with acute cardioembolic stroke.

We detected oscillating thromboemboli at the extracranial internal carotid artery (ICA) by duplex carotid ultrasonography in patients with acute cardioembolic stroke. Using B-mode ultrasonography, we evaluated the extracranial ICA in 11 patients with acute cardioembolic ICA occlusion. A homogeneous, elastic, oscillating intraluminal mass echo originating in the extracranial ICA extended distally in 5 (46%) of these patients. The echoes moved quickly and distally during the systolic phase of the cardiac cycle and returned slowly to the original position during the diastolic phase. We performed a postmortem study 24 days after stroke onset in 1 patient with an oscillating intraluminal mass echo that had been demonstrated by duplex ultrasonography. The ICA lumen was obstructed with a fresh string-like thrombus. The findings of oscillating intraluminal mass echo may help establish a diagnosis of acute embolic ICA occlusion.

Acute Disease↗

Granular cell tumor of the pituitary stalk.

A 52-year-old woman, who had been treated for Parkinson disease for 2 years, was found to have a suprasellar granular cell tumor. The clinical and pathological features, as well as some of the nosologic problems of this rare tumor of the neurohypophysis are briefly discussed.

Female↗

The pattern of alteration in flow velocity in the recanalized artery is related to left ventricular recovery in patients with acute infarction and successful direct balloon angioplasty.

OBJECTIVES: We evaluated the relationship between alterations in coronary flow velocity during the acute phase of acute myocardial infarction (AMI) and the recovery of left ventricular wall motion in patients who underwent successful primary angioplasty. BACKGROUND: The status of the coronary microcirculation is the major determinant of the prognosis of patients who have had successful reperfusion after AMI. Animal studies have shown that dynamic changes in regional flow are associated with the extent of infarction. Evaluation of alterations in coronary flow velocity in infarcted arteries may provide information about microcirculatory damage. METHODS: Flow velocity of the distal anterior descending artery was continuously monitored with the use of a Doppler guide wire immediately after recanalization for 18 +/- 4 h in 19 patients who underwent successful primary angioplasty after anterior AMI. Subjects were divided into two groups on the basis of the time course of alterations in average peak velocity (APV). Group D consisted of patients who had progressive decreases in APV through the next day (n = 9), and Group I comprised patients with an increase in APV after a transient decline (n = 10). Ejection fraction (EF) and regional wall motion (RWM) were assessed by left ventriculography performed on admission and at discharge. RESULTS: The APV at the end of monitoring was greater in group I than in group D. In group I, EF and RWM were significantly improved at discharge. The change in EF was greater in group I than in group D (17 +/- 9% vs. 4 +/- 9%, p = 0.007), as was the change in RWM (0.96 +/- 0.23 vs. 0.13 +/- 0.36 SD/chord, p < 0.0001). CONCLUSIONS: The alteration in flow velocity in recanalized infarcted arteries is related to left ventricular recovery. A progressive decrease in velocity after angioplasty implies no reflow, which is associated with a poor recovery of left ventricular function. Reperfusion injury may account in part for this phenomenon.

Aged↗

Placement of endosteal implants combined with chin bone onlay graft for dental reconstruction in patients with grafted alveolar clefts.

Endosteal implants were inserted into grafted alveoli after particulate cancellous bone and marrow grafting in seven patients with cleft lip or palate in conjunction with simultaneous chin bone onlay grafting. In these patients, the alveolar bone height of the bony bridge was insufficient when evaluated by both computed tomographic and periapical radiographic images. The age at first implant surgery ranged from 14 to 28 years. Although four of the seven patients had an uneventful course, three had wound dehiscence, and in all but one of them the exposed chin bone underwent partial or total necrosis. Ultimately all seven implants integrated into the bone, and the alveolar bone height was increased in all but one patient. The results indicate that chin bone onlay grafting with simultaneous implant insertion is useful in patients with cleft lip or palate with insufficient alveolar bone height.

Adolescent↗

Side-to-side differences of the common carotid artery diameter in presence of asymmetry of the circle of Willis or different vasculopathies.

Based on angiographic and carotid ultrasonographic findings in 60 patients with stroke or other diseases, we studied what factors affected the side-to-side differences of the common carotid artery diameter (CCAD). The side-to-side differences of the CCAD were within 0.7 mm in patients with normal cerebral angiogram, but a difference above 0.7 mm was found in many patients with asymmetry of the circle of Willis or different vasculopathies, such as the carotid artery occlusion, cerebral arteriovenous malformation and aortitis.

Aortitis↗

Stellate ganglion block does not change the tympanic membrane temperatures of either block or unblock sides in male volunteers.

STUDY OBJECTIVES: To test the effect of stellate ganglion block on tympanic membrane temperatures. DESIGN: Prospective, observational study. SETTING: Department of Anesthesia, Yamanashi Medical University, Yamanashi, Japan. SUBJECTS: 7 healthy male volunteers. INTERVENTIONS: Stellate ganglion block, 6 ml of 1% mepivacaine hydrochloride, was administered. MEASUREMENTS AND MAIN RESULTS: Application of temperature probes (right and left tympanic membranes, eight adhesive right skin-surface temperatures at the chest, upper arm, digital fingertip, lateral calf, thigh, and great toe) was followed by a 30-minute control period. Temperatures were recorded every 15 minutes for 30 minutes before stellate ganglion block and every 5 minutes for 40 minutes after the block. The right tympanic membrane temperature increased slightly but not significantly compared with the left tympanic membrane temperature 10 minutes after stellate ganglion block and subsequently. Right skin-surface temperature gradients at the upper limb decreased slightly but not significantly after stellate ganglion block. Similarly, right skin-surface temperature gradients at the lower limb decreased slightly but not significantly after stellate ganglion block. CONCLUSIONS: Stellate ganglion block does not change the tympanic membrane temperatures of either block or unblock sides.

Adult↗

The use of BRM-activated killer cells in adoptive immunotherapy: a pilot study with nine advanced cancer patients.

Adoptive immunotherapy using MHC-nonrestricted-lymphocytes, peripheral blood gammadelta T cells and NK cells was devised. Peripheral blood mononuclear cells (3 x 10(7)) were selected by immobilization to anti-CD3 monoclonal antibody for 4 days and cultured for 2 weeks in the presence of IL-2. Thereafter they were reactivated by 500 U/ml of IFN-alpha and 1000 U/ml of IL-2 for 1 hour. Enhancement of NK and LAK activities was confirmed. Peripheral blood gammadelta T cells proliferated in response to immobilized anti-CD3 antibody (3% to 30%). Approximately 6 x 10(9) BRM-activated killer (BAK) cells composed of CD56+ gammadelta T cells and CD56+ NK cells, were dispensed to cancer patients via intravenous drip infusion. Nine patients were treated with BAK cells every 2 weeks or every month on an outpatient basis. During the course of adoptive immunotherapy, the crossed affinity immunoelectrophoresis (CAIE) pattern of serum immunosuppressive acidic protein (IAP) was analysed. Both the production and glycosylation pattern of IAP is changed in response to tumor enlargement and may therefore act as a marker of the disease progression. During the course of BAK therapy, the glycosylation IAP pattern of 6 patients changed from tumor (T) to normal (N). In addition, the performance status of all patients was maintained at 90-100% of the Karnofsky scale and any side effects including fever were not observed during treatments with BAK cells. Moreover, the overall quality of life (QOL) of the patients, scored at the Face scale was favorable. In addition, blood levels of activated gammadelta T cells producing IFN-gamma were assayed as an indication marker of BAK therapy. The normal range of IFN-gamma producing gammadelta T cells comprised 6.9 +/- 0.9% of peripheral blood mononuclear cells (PBMC), according to a single cell FACScan analyses of PBMCs derived from normal individuals. IFN-gamma producing gammadelta T cells of Patients No. 8 and 9, who received extensive chemotherapy before initiation of BAK therapy, comprised only 0.2% and 2% of PBMC, respectively. These patients died 3 and 6 months after beginning BAK therapy. Peripheral blood gammadelta T cells of Patients Nos. 1-7 proliferated in response to immobilized anti-CD3 antibody and the frequency of IFN-gamma producing gammadelta T cells in PBMC preparation of these patients were over 3% before initiation of BAK therapy. Since our data show a positive correlation between survival time and initial gammadelta T cell counts, a low frequency of these cells may contraindicate BAK therapy.

Adult↗