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Biomedical subjects

R Suzuki

Publications and source records attributed to R Suzuki.

At least 361 records · Page 20Linked to original sources

Meiotic abnormalities of c-mos knockout mouse oocytes: activation after first meiosis or entrance into third meiotic metaphase.

In Xenopus oocytes, Mos activates the mitogen-activated protein kinase (MAPK) signal transduction cascade and regulates meiosis. In mammalian oocytes, however, the functions of Mos are still unclear. In the present study, we used c-mos knockout mouse oocytes and examined the roles of Mos in mouse oocyte maturation and fertilization, including whether Mos controls MAPK and maturation promoting factor (MPF) activity. The kinetics of germinal vesicle breakdown (GVBD) and the first polar body emission were similar in wild-type, heterozygous mutant, and homozygous mutant mice. Activities of MPF were also not significantly different among the three genotypes until the first polar body emission. In contrast, MAPK activity in c-mos knockout oocytes did not significantly fluctuate throughout maturation, and the oocytes had abnormal diffused spindles and loosely condensed chromosomes, although a clear increase in MAPK activities was observed after GVBD in wild-type and heterozygous mutant oocytes that had normal spindles and chromosomes. After the first polar body emission, 38% of c-mos knockout oocytes formed a pronucleus instead of undergoing second meiosis, indicating the crucial role of Mos in MPF reactivation after first meiosis. When oocytes that reached second metaphase were fertilized or stimulated by ethanol, many c-mos knockout oocytes emitted a second polar body and progressed into third meiotic metaphase instead of interphase, although all fertilized or activated oocytes in the heterozygote progressed to interphase, indicating that Mos deletion leads to compensatory factors that might not be degraded after fertilization or parthenogenetic activation. These results suggest that Mos is located upstream of MAPK in mouse oocytes as in Xenopus oocytes but is independent of MPF activity, and that Mos/MAPK is not necessary go GVBD and first polar body emission. Our results also suggest that Mos plays a crucial role in normal spindle and chromosome morphology and the reactivation of MPF after first meiosis.

Animals↗

Clinicopathologic study of PRAD1/cyclin D1 overexpressing lymphoma with special reference to mantle cell lymphoma. A distinct molecular pathologic entity.

Mantle cell lymphomas (MCLs) are frequently associated with the overexpression of PRAD1/cyclin D1, activated by 11q13 translocation and its molecular counterpart BCL-1 gene rearrangement. We recently described the correlation of positive nuclear staining using monoclonal antibody against a PRAD1/cyclin D1 product with mRNA overexpression in MCLs. In the present study, we immunohistochemically investigated the PRAD1/cyclin D1 protein in a large series of 334 lymphoproliferative disorders, including 39 cases of MCLs on paraffin sections. Based on the cyclin D1 positivity, CD5 expression, and the morphologic features of the tumor tissue, four groups of MCL-related lesions were identified among the B-cell lymphomas examined: 36 cases with cyclin D1 overexpression, 35 (95%) of which exhibited CD5-positivity and MCL-morphology (Group 1); four cases of lymphomas with MCL morphology and CD5 expression but lacking cyclin D1 overexpression (Group II); four cases of lymphomas without cyclin D1 overexpression and surface CD5 but that fall within the morphologic boundaries of MCLs (Group III); and 11 cases of CD5-positive diffuse large cell lymphomas without cyclin D1 overexpression (Group IV). The Group I cases demonstrated quite homogeneous clinicopathologic features identical to those of MCLs. This group showed a poor prognosis (11% had 5-year survival), which is highly contrasted with that of Group II (100%). Although the four groups of MCL-related lesions sometimes overlapped in their histologic or phenotypic spectrums, each appeared to show distinct clinicopathologic and prognostic profiles. Our study provides a basis for further clarification of the nature of the neoplasms of Groups II, III, and IV. Moreover, this comprehensive study may indicate that the overexpression of PRAD1/cyclin D1 is biologically essential to defining MCLs.

Aged↗

Impaired endothelium-dependent relaxation in rabbit pulmonary artery after subarachnoid hemorrhage.

We investigated the changes in endothelial function of pulmonary as well as basilar artery after experimental subarachnoid hemorrhage (SAH) induced by cisternal blood injection in rabbits. The animals were killed on day 2 and day 7, and the mechanical responses were determined on transverse strips of the main pulmonary artery and rings harvested from the basilar artery. To examine the role of the vagal nerve, we cut the left vagal nerve immediately before injecting cisternal blood. Relaxation response of pulmonary and basilar arteries to acetylcholine (ACh) and A23187 were abolished after endothelial removal and reality inhibited by either NG-nitro-L-arginine (NOARG) or methylene blue (MB). Indomethacin failed to modify these relaxation responses. Relaxation response of the main pulmonary artery strips to ACh was significantly (p < 0.05 and p < 0.01) attenuated on day 2 in 6 of 12 rabbits. In the remaining 6 rabbits, relaxation was not affected. No change in relaxation responses to A23187 and sodium nitroprusside (SNP) was observed in any of the 12 cases. In the vagotomized rabbits no decreased response to ACh was observed. On day 7, relaxation response to ACh returned to normal. ACh also produced decreased relaxation in basilar artery rings on day 2 with no change in A23187- and SNP-induced relaxation. Contractile responses of pulmonary and basilar arteries to norepinephrine (NE), endothelin-1 (ET-1), 5-hydroxytryptamine (5-HT), and U46619 were not affected after SAH. These results suggest that less functional muscarinic receptors that produce/release less endothelium-derived relaxation factor [EDRF/nitric oxide (NO)] are involved in causing the reduced relaxation of pulmonary and basilar arteries after SAH and the vagal nerve may play a role in regulating the receptor-mediated, endothelium-dependent relaxation in the main pulmonary artery after experimental SAH.

Acetylcholine↗

A method of measuring dipalmitoylphosphatidylcholine (DPPC) by high-performance liquid chromatography (HPLC): effect of dexamethasone on DPPC secretion in fetal rat alveolar type II cell culture.

OBJECTIVE: To establish a method by which to measure dipalmitoylphosphatidylcholine (DPPC), which is the most prevalent phospholipid in lung surfactant, by high-performance liquid chromatography (HPLC), and to measure DPPC secretion in type-II alveolar cell culture to determine whether glucocorticoid has a direct accerelating effect. METHOD: Type-II alveolar cell suspensions were made with fetal rat lungs and then cultured. Dexamethasone, (10(-9), 10(-8) M) was added to some of the culture dishes. DPPC was extracted from the culture medium, purified, and measured by high-performance liquid chromatography (HPLC). RESULTS: In the measurements of DPPC, the specificity of isolation and measurement parity were excellent [coefficient of variation: intraassay; 5.66% (0.005 mg/ml), 25.37% (0.05 mg/ml): interassay; 8.35% (0.005 mg/ml), 0.08% (0.05 mg/ml)]. The DPPC concentration in the culture dishes of the dexamethasone was not significantly different than that of the control dishes (Student's t-test). CONCLUSION: The above results prove that dexamethasone does not directly stimulate lung alveolar type-II cells.

1,2-Dipalmitoylphosphatidylcholine↗

Xe-CT in cerebrovascular disease and moyamoya disease.

(1) Negative response to acetazolamide challenge test using Xe-CT is a reliable indicator for identifying the hemodynamic compromise. (2) The hemodynamic compromise may be a cause of TIAs in some patients with chronic cerebrovascular occlusive diseases. (3) The brain suffering from hemodynamic compromise actively works to induce collateral blood channels.

Acetazolamide↗

Protective activity of rabbit polyclonal anti-idiotype antibody against Leptospira interrogans infection in hamsters.

We prepared an anti-idiotype (Id) antibody against leptospirosis. Serum from rabbit immunized with monoclonal antibody (MAb) LW2, which reacted to the main protective antigen prepared from Leptospira interrogans serovar lai, inhibited agglutination of the organism by MAb LW2. The immune rabbit serum was applied to a column coupled with normal mouse IgG as a ligand (first column), and the unbound fraction eluted was applied to a column coupled with MAb LW2 as a ligand (second column). The bound fraction (anti-Id antibody) eluted from the second column inhibited the binding of MAb LW2 to sonicated leptospiral cells in ELISA. Mice produced antibodies against Leptospira by intraperitoneal immunization with the anti-Id antibody at doses of 2 mu g/mouse or more. Hamsters were protected by immunization with the anti-Id antibody at doses of 2 and 20 mu g/hamster from the lethal infection of Leptospira. This is the first report concerning the use of an anti-Id antibody against leptospirosis.

Agglutination↗

Effects of long-term oral administration of amiodarone on the ventricular repolarization of rabbit hearts.

The chronic effects of amiodarone on ventricular repolarization were investigated in Langendorff-perfused rabbit hearts in comparison with the acute effects of other Class III antiarrhythmic drugs. Forty to fifty electrograms were recorded through modified bipolar electrodes from the anterior to the lateral epicardial surface of the ventricles under His-bundle pacing (1.0 Hz). In control hearts, epicardial activation proceeded from the apex to the base. The interval from the initial sharp negative deflection of the QRS complex to the apex of the T-wave (Q-aT), which reflects the action potential duration (APD) at the recording site, was longest in the apex and shortest in the base. Therefore, repolarization proceeded from the base to the apex. In hearts treated with oral amiodarone (100 mg/kg, 4 weeks), Q-aT was uniformly prolonged by 14-16% throughout the entire mapped area, whereas the activation sequence was unaffected, and a normal Q-aT gradient was well preserved from the apex to the base. The spatial inhomogeneity of left ventricular repolarization was not enhanced by drug treatment. Acute application of sotalol (30 mumol/L), E-4031 (0.1 mumol/L) or MS-551 (1.0 mumol/L) caused a much greater Q-aT prolongation in the apex than in the base, resulting in a marked enhancement of the spatial inhomogeneity of repolarization. These findings suggest that the propensity of chronic amiodarone to induce torsade de pointes less often than other Class III agents may result at least in part from its favorable effect on the spatial homogeneity of ventricular repolarization.

Administration, Oral↗

Antibodies to the 37,000-Mr tryptic fragment of islet antigen were detected in Japanese insulin-dependent diabetes mellitus patients.

Sera from 30 Japanese insulin-dependent diabetes mellitus (IDDM) patients of short duration were examined to determine whether they had antibodies to proteolytic fragments of islet antigen, the molecular weights of which were 37,000 and/or 40,000 Mr (37KAb). The median age and disease duration of the patients were 13 (range 6-22) years old and 12 (range; 0-24) months, respectively. Twelve out of the 30 IDDM patients (40%) had 37KAb, while none of the 16 control subjects was positive for 37KAb. The frequency of the 37KAb was not correlated with disease duration tested. We further investigated the antibodies to ICA512, by radioligand binding assay, which has been proposed to be a target antigen for the 37 KAb. Twenty-two (73.3%) patients had antibodies to ICA512 (ICA512AA), but none of the control subjects did. The levels of ICA512AA, which were described as indexes using standard sera, were significantly higher in the patients than in the control subjects (1.436 +/- 2.674 and 0.001 +/- 0.002, respectively, P < 0.05). The frequency of antibodies to glutamic acid decarboxylase 65 (GAD65Ab) was also higher in the patients than in the control subjects (70% and 0%, respectively), but 7 out of 9 GAD65Ab-negative patients had ICA512AA and/or 37KAb. Since 93% of the IDDM patients had at least one of these antibodies, combined analysis with 37KAb, ICA512AA, and GAD65Ab facilitates diagnosis of Japanese IDDM.

Adolescent↗

[Prostaglandins increase the response of intraocular muscle and outflow facility of the eye].

The function and sites of action of prostaglandins (PGs) vary in different animal species and tissues. In this study the effects of PGs (E1, E2, F2 alpha ,D2) on intraocular muscles and outflow facility of the eye were investigated, using enucleated bovine eyes. None of these PGs exogenously applied influenced the neuromuscular transmission. By contrast, after treatment with indomethacin, all PGs tested contracted the muscle much more than in the absence of indomethacin, and under these conditions the PGs potentiated responses to cholinergic nerve stimulation. Whereas PGF2 alpha was less potent in the absence of indomethacin, PGF2 alpha had more potent action primarily on nerves and partly on muscles after treatment with indomethacin. PGs also increased outflow facility of the eye, after the treatment with indomethacin. In order to understand the site and action of PGs, pretreatment with indomethacin may be useful in the intraocular muscle and outflow facility of the eye.

Animals↗

Spinal arachnoid cyst developing after surgical treatment of a ruptured vertebral artery aneurysm: a possible complication of topical use of fibrin glue. Case report.

A case is reported of a 59-year-old man with a spinal arachnoid cyst accompanied by spinal arachnoiditis. The patient developed symptoms after treatment for a ruptured vertebral artery aneurysm, in which fibrin glue was used for reconstruction of the suboccipital bone defect. It is believed that the fibrin glue may have played a role in forming the arachnoid cyst. The authors urge the readers to keep in mind the possibility of subclinical spinal arachnoiditis in the patients with aneurysmal subarachnoid hemorrhage and suggest that care should be taken to avoid any possible adverse effect of fibrin glue.

Administration, Topical↗

Chemical modification of PA-48153C, a novel immunosuppressant isolated from Streptomyces prunicolor PA-48153.

5beta-Methoxy (20), 14-methyl (24), 14,14-dibromo-15-nor (25), 8-O-acyl (26-45), 8-O-alkyl (46), 8-O-alkoxycarbonyl (47, 48), and 8-O-carbamoyl (49) derivatives of PA-48153C, a novel immunosuppressant isolated from fermentation products of Streptomyces prunicolor PA-48153, were prepared. These compounds were found to retain the inhibitory activity on the responses of both T and B cells to mitogens. Among them, the C-8 hexanoate 28 showed potent suppressive effects on mitogen responses with less cytotoxicity to EL4 cells and was selected for in vivo evaluation.

Animals↗

[Prostate cancer screening in total health care check--using serum PSA and AUA score].

From April 1994 to February 1995, we studied prostate cancer screening at Shakaihoken Hazu Hospital and Health Care Center. Among 1,838 men, over 55, who had taken the total health care check, 857 applicants had had prostate cancer screening, using serum PSA (Delia kit; normal range < 11.7 ng/ml) and AUA voiding symptom score and bothersome score. According to the serum PSA level, they were divided into 4 groups, 11 with 8 ng/ml or more indicating requirement of further examination, 29 with 4-8 ng/ml indicating requirement of observation, 100 with less than 4 ng/ml and AUA score (approximately more than 10) indicating voiding disturbance and the other 717 were normal; Of 11 further examined cases, 6 applicants underwent random biopsy. We found 3 with prostate cancer (0.35%).

Aged↗

[A study of the significance of serum beta 2-microglobulin levels in patients with multiple myeloma--analyzes as a marker of renal dysfunction and as a marker of tumor cell mass].

Renal involvement known as a myeloma kidney is often observed in patients with multiple myeloma (MM). This complication has been recognized as one of the most important prognostic factors in this disease. Serum beta 2-microglobulin (S beta 2-m) has been also recognized one of the prognostic factor that reflects both a glomerular infiltration rate and a volume of neoplastic cells, because beta 2-m usually can be produced by the neoplastic lymphoid cells. To clarify the significance of the S beta 2-m in MM, we compared S beta 2-m levels and the clinical stage, with another clinical parameters for renal function such as 24 hr creatinine clearance (24 hr Ccr), N-acetyl-beta-glucosaminidase (NAG) levels in urine and serum alpha 1-microglobulin (S alpha 1-m) levels. The elevated S beta 2-m levels were commonly observed not only in patients with stage IIIB, but also in stage IA, IIA and IIIA (76%) who have normal renal function judged by the serum nitrogen or creatine levels. S beta 2-m levels correlated with 24 hr Ccr the most, then correlated with S alpha 1-m levels and less correlated with NAG levels in urine. Although a single elevation of S beta 2-m levels with other normal findings of renal parameters was found only in three out of 30 MM patients, the S beta 2-m levels in these patients did not change after the chemotherapy which had led to the diminution of serum M-protein. Together with these results, it was suggested that the S beta 2-m levels mainly reflect the renal dysfunction even if it stays in the subclinical stage, and reflect less the number of neoplastic cells in MM patients.

Biomarkers↗

[A special form of Stargardt's disease/fundus flavimaculatus].

Stargardt's disease is a bull's-eye macular dystrophy with the characteristic appearance of a perifoveal lesion. We have observed four cases of an autosomal recessive disease with fundus features undistinguishable from Stargardt's disease, but with a different nature and much poorer prognosis. One case typical of Stargardt's disease characterized with macular degeneration showed a bull's-eye with dark choroid. Sixteen years later, the same eye developed bone corpuscle pigmentation in the periphery with non-recordable electroretinogram. The other three cases were members of a single family. They showed typical macular degeneration consistent with Stargardt's disease but had peripheral degeneration as well. Taking into account that there is a great diversity of retinal functions in Stargardt's disease, these features are different from those reported previously. Stargardt's disease should not be considered as a single clinical entity with a fair prognosis.

Child↗

Atraumatic loose shoulder: the treatment by pectoralis major muscle transfer.

From 1975, 40 shoulders of 34 patients with a loose shoulder were operated on by pectoralis major transfer. The insertions of the clavicular and sternal portions were transferred to the inferior angle of the scapula to bring the glenoid cavity upwards. The follow-up period was 5.3 years on average, and complaints of dullness of the shoulder, feeling of subluxation and dullness of the arm had decreased. However, complaints of dullness of the shoulder girdle had increased at follow-up. The inferior instability had improved in all but four shoulders because this method brings the glenoid cavity upwards and the changes of the upward rotating angle of the scapula were confirmed by roentgenographic investigations. The study of the tracking movement pointed out that this method did not affect the motion of the shoulder, and the high activity of the transferred pectoralis major muscle during the movement was thought to play an important role in reducing inferior instability. This method is most recommended for a patient who has multidirectional instability and can subluxate the head antero-inferiorly by the pectoralis major muscle, but it is not recommended for athletes as the power of the shoulder adductor is reduced to some extent after surgery.

Adult↗