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Biomedical subjects

T Kubo

Publications and source records attributed to T Kubo.

At least 289 records · Page 16Linked to original sources

Effects of long-term treatment with pimobendan on neurohumoral factors in patients with non-ischemic chronic moderate heart failure.

To evaluate the effects of the addition of pimobendan to an optimal basic regimen on plasma levels of neurohumoral factors in patients with non-ischemic, moderate heart failure during 2-year follow-up. This prospective, observational study involved 16 patients with non-ischemic, moderate heart failure [New York Heart Association (NYHA) functional class IIM-III] receiving an optimal basic regimen of digitalis, diuretics and angiotensin-converting enzyme inhibitor. Eight patients (Group P) were also administered pimobendan at a dose of 2.5 or 5 mg daily, while the other 8 served as controls (Group C). After 3 months of pimobendan administration, the plasma levels of norepinephrine and atrial natriuretic peptide and brain natriuretic peptide decreased and left ventricular ejection fraction improved. After 1 year, the cardiac symptoms, assessed using the Specific Activity Scale as well as the NYHA functional class, improved and the left ventricular end-diastolic diameter decreased. These improvements in Group P were maintained for 2 years. However, in Group C, the cardiac symptoms and the neurohumoral factor levels remained unchanged or deteriorated during this study, and one patient died of heart failure. Long-term combination therapy with the optimal basic regimen and pimobendan has potentially beneficial effects on neurohumoral factor levels and cardiac symptoms in patients with non-ischemic, chronic moderate heart failure.

Adult↗

Control of delivered gene expression in chondrocytes using heat shock protein 70B promoter.

OBJECTIVE: To investigate whether the expressions of delivered Escherichia coli beta-galactosidase (LacZ) gene and transforming growth factor-beta1 (TGF-beta1) gene are regulated by the stress response of human chondrocyte-like cells (HCS-2/8) when heat shock protein 70B (HSP70B) promoter is inserted into the adenovirus vector. METHODS: Two adenovirus vectors that contain either LacZ gene or TGF-beta1 gene regulated by HSP70B promoter were constructed. One of the adenovirus vectors was added to the culture of HCS-2/8 and gene transduced cells were produced. We applied heat stress (43 degrees C) to the transduced cells for 2 h and examined whether the expression of transduced LacZ and TGF-beta1 genes is affected by the stress, using 5 bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining, measurement of beta-galactosidase activity, Northern blotting, and ELISA. RESULTS: The percentage of X-gal positive stained cells in LacZ gene-delivered cells with heat stress was significantly higher than in controls (no heat stress). With heat stress, beta-galactosidase activity increased significantly, and the band of exogenous TGF-beta1 mRNA became more apparent and the expression was maintained during the 24 h monitoring period. TGF-beta1 level in culture supernatant of TGF-beta1 gene-delivered cells with heat stress (5477.3+/-321.1 pg/ml) was significantly higher than in the controls (853.2+/-29.2 pg/ml). CONCLUSION: HSP70B promoter could regulate the expression of delivered genes according to the intensity of heat stress.

Adenoviridae↗

Pedicle bone grafting versus transtrochanteric rotational osteotomy for idiopathic osteonecrosis of the femoral head--four patients with both procedures.

The clinical and radiographic results of vascularized pedicle iliac bone grafting (PBG) and Sugioka's transtrochanteric anterior rotational osteotomy of the femoral head (ARO) for idiopathic osteonecrosis of the femoral head were compared. Four male patients with bilateral osteonecrosis of the femoral head were treated with PBG in the first hip and with ARO in the second. All patients had stage 2 or 3 involvement according to Ficat's classification. Average age at the time of PBG and ARO was 42 and 43 years, respectively. Average follow-up of PBG and ARO was 7.5 and 5.7 years. At final follow-up, the average Harris hip scores of PBG and ARO were 73 and 85, respectively. Collapse was observed in 3 PBG hips and in 1 ARO hip. Three patients were more satisfied with the ARO procedure than with the PBG treatment, and one patient was undecided. ARO was considered better surgical treatment than PBG from both a clinical and radiological perspective.

Adult↗

Transplacental exposure to antipsychotic drugs during pregnancy and megacystis in the fetus.

Urinary retention is an adverse effect of antipsychotic drugs that has not been previously reported in the fetus. We have diagnosed megacystis in a fetus possibly caused by transplacental exposure to the antipsychotic drugs being administered to the mother. Two weeks after the mother stopped taking the drugs, the size of the enlarged fetal urinary bladder returned to normal. Sonographic examination of the neonate revealed an anatomically normal urinary tract, with a normal bladder capacity and urination.

Adult↗

[Detection of culprit lesion in patients with unstable angina pectoris by using ATP thallium-201 myocardial SPECT].

The purpose of this study is to determine the diagnostic accuracy for detection of culprit lesions in patients with unstable angina. Both ATP 201Tl SPECT and coronary angiography were performed in 51 patients with unstable angina pectoris within a week since the last attack. SPECT images were divided into 17 segments and the regional uptakes were scored semiquantitatively (0 = normal to 3 = no activity) and compared with the coronary angiographic findings. ATP 201Tl SPECT revealed decreased uptakes in 54 of 56 culprit lesions. The sensitivity, specificity and accuracy for detection of culprit lesions were 96.4%, 89.5% and 92.4%, respectively. Although adverse effects during ATP administration were complicated in 28 (54.9%) patients, all the complications were mild and resolved within two minutes. ATP 201Tl SPECT is sensitive and reliable method for detecting culprit lesions and can be performed safely even at acute phase in patients with unstable angina pectoris.

Adenosine Triphosphate↗

Autosomal recessive hydrocephalus due to congenital stenosis of the aqueduct of sylvius.

Isolated hydrocephalus due to congenital stenosis of the aqueduct of Sylvius is almost always an X-linked recessive inherited condition. We describe a brother and sister with isolated hydrocephalus from congenital aqueductal stenosis. We believe that these two occurrences represent a rare autosomal recessive form of this abnormality. In assessing a first known occurrence of hydrocephalus with stenosis of the aqueduct of Sylvius in a family, the rare possibility of autosomal inheritance must be considered in genetic counselling.

Abortion, Therapeutic↗

[Phase I study of a combination chemotherapy of nedaplatin and cisplatin].

A new platinum complex, nedaplatin, has been reported to be effective for both ovarian and cervical cancers. We designated a phase I dose-escalation study of a combination chemotherapy of nedaplatin and cisplatin to investigate the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Six patients, including two with advanced cervical cancer, three with ovarian clear cell adenocarcinoma and one with endometrial clear cell adenocarcinoma, were enrolled in this study. The doses of the two agents were escalated alternatively, i.e., a tandem method, from 40 to 80 mg/m2 by 20 mg/m2. Nedaplatin and cisplatin were administrated by intravenous drip infusion and repeated after an interval of at least 4 weeks, as a rule. The major toxicity observed was hematotoxicity. One of the 6 patients dropped out of this study because of severe hematotoxicity after 80 mg/m2 of nedaplatin and 60 mg/m2 of cisplatin were administered. With a dose of 80 mg/m2 nedaplatin and 80 mg/m2 cisplatin, severe neutropenia was found in all 6 patients, and thrombocytopenia and anemia were found in 1 patient, respectively. A slight hearing loss was detected by audiometry in 5 patients, but no one was inconvenienced in daily life. Mild nausea and vomiting were also observed in all 6 patients. In conclusion, the DLT of this combination therapy was hematotoxicity and the MTD was 80 mg/m2 for nedaplatin and 60 mg/m2 for cisplatin, respectively. Thus, 60 mg/m2 of nedaplatin and 60 mg/m2 of cisplatin may be recommended for combined administration.

Adenocarcinoma, Clear Cell↗

Unilateral labyrinthectomy downregulates glutamate receptor delta-2 expression in the rat vestibulocerebellum.

The differential display method was applied to identify genes expression of which is altered in the flocculus after unilateral labyrinthectomy (UL). Total RNA from sham operated and labyrinthectomized rat flocculi was isolated, amplified by PCR using an arbitrary primer set and separated by electrophoresis on a polyacrylamide gel. PCR products the amounts of which were significantly lower in samples from labyrinthectomized animals than those from controls, were cut out of the gel and sequenced. One of the cDNA fragments showed 100% nucleotide sequence identity to the rat glutamate receptor (GluR) delta-2 subunit mRNA. In situ hybridization autoradiography showed that GluR delta-2 mRNA expression was intensely located to the floccular Purkinje cell layers. Furthermore, northern blot analysis showed that the delta-2 mRNA expression was decreased for at least two days after UL in accordance with diminishing UL-induced behavioral deficits. Therefore, it is suggested that the downregulation of delta-2 mRNA is involved in vestibular compensation. UL-induced spontaneous nystagmus (SN) was then examined in GluR delta-2 mutant mice. The frequency of SN in mutant mice was significantly more than that in wild mice until 12 h after UL. GluR delta-2-associated synaptic efficacy may be changed for the induction of vestibular compensation at the initial stage.

Animals↗

Morphology and function of human benign tumors and normal thyroid tissues maintained in severe combined immunodeficient mice.

In the improved SCID (severe combined immunodeficient) mice, various human benign tumors of the head and neck region were well maintained morphologically and functionally for 3 years until the experiments were terminated, e.g. transplanted parathyroid adenoma secreted parathyroid hormone (PTH) in the SCID mice for more than 1 year. Normal human thyroid tissue was also well maintained in the SCID mice for 3 years. Rapid and high uptake of radioiodine into the transplanted human thyroid tissue was observed. Furthermore, transplanted human thyroid tissue secreted thyroid hormone (T3) and T3 secretion was stimulated by the injection of human thyroid stimulating hormone (TSH). These findings suggest that the improved SCID mice will provide an invaluable experimental system for investigating the function of normal human tissues and the influence of endogenous and exogenous factors on human tissues.

Adenoma↗

Auditory evoked off-response: its source distribution is different from that of on-response.

Offset auditory responses were investigated by electroencephalography mainly in the 1970s, but since then no particular attention has been paid to them. Among the studies using magnetoencephalography (MEG) devices there are, to our knowledge, only three studies of the auditory off-response, and no significant variance has ever been observed between the source locations of on- and off-responses elicited from pure tones. We measured auditory evoked magnetic fields (AEFs) to various frequency pure tone stimulation in 5 healthy subjects with a 122-channel helmet-shaped magnetometer, and compared the distributions of the source locations of auditory N100m-Off (magnetic off-response around 100 ms) with those of N100m-On. Their spatial distributions were quite close to each other, and yet they were significantly different.

Acoustic Stimulation↗

Effects of water on the alpha-beta transformation kinetics in san carlos olivine

In experiments at 13.5 gigapascals and 1030 degreesC, the growth rate of wadsleyite, which forms from transformation of olivine, was substantially enhanced by the presence of water. Wadsleyite had a low dislocation density and subgrain boundaries in wet runs. Water enhanced the dislocation recovery in wadsleyite and therefore caused inelastic relaxation of the localized pressure drop associated with the transformation, resulting in an increase of the growth rate in wet runs. These results imply that even a small amount of water of 0. 05 weight percent can weaken wadsleyite in the mantle.

Journal Article↗

Multiple roles of interferon-gamma in the mediation of interleukin 12-induced tumor regression.

Administration of recombinant interleukin 12 (IL-12) induces tumor regression that is associated with T-cell infiltration in the OV-HM ovarian carcinoma and CSA1M fibrosarcoma models. After confirming the blocking of regression by injection of anti-IFN-gamma monoclonal antibody (mAb), we investigated the mechanisms underlying the requirement of IFN-gamma in T-cell migration and tumor regression. T-cell migration was inhibited by injection of anti-IFN-gamma mAb to OV-HM tumor-bearing mice prior to IL-12 treatment. We examined, using the lymphoid cell migration assay, whether IFN-gamma is required for enhancing the migratory capacity of T cells or the T cell-accepting potential of tumor masses during IL-12 treatment. Spleen cells from IL-12-treated or untreated OV-HM-bearing mice were stained in vitro with a fluorescein chemical and transferred i.v. into OV-HM-bearing mice that were not treated with IL-12. Migration of donor cells was quantitated by counting the number of fluorescent cells on cryostat sections of tumor masses from recipient mice. Compared to spleen cells from OV-HM-bearing mice that were not treated with IL-12, enhanced migration was observed for cells from IL-12-treated OV-HM-bearing mice. Anti-IFN-gamma pretreatment of donor mice before IL-12 treatment did not reduce the migratory capacity of T cells, whereas migration was markedly inhibited in recipient mice injected with anti-IFN-gamma. Anti-IFN-gamma pretreatment decreased vascular cell adhesion molecule-1 (VCAM-1)-/intercellular adhesion molecule-1 (ICAM-1)-positive blood vessels at tumor sites. Consistent with this, migration was also inhibited by treatment of recipient mice with either anti-VCAM-1 or anti-ICAM-1 mAb. In contrast to the OV-HM model, T-cell migration was not affected in the CSA1M model following preinjection of anti-IFN-gamma mAb. In this model, VCAM-1-/ICAM-1-positive blood vessels existed even after anti-IFN-gamma treatment, although tumor regression was completely inhibited. These results indicate that IFN-gamma plays two distinct roles in expressing the antitumor efficacy of IL-12: one is to support the T-cell acceptability of tumor masses, and the other is to mediate the antitumor effects of migrated T cells.

Animals↗

Evidence that angiotensin II, endothelins and nitric oxide regulate mitogen-activated protein kinase activity in rat aorta.

We measured the activity of mitogen-activated protein (MAP) kinases, enzymes believed to be involved in the pathway for cell proliferation, in rat aortic strips with or without endothelium, and examined effects of angiotensin receptor antagonists, endothelin receptor antagonists and nitric oxide (NO)-related agents. Endothelium removal produced an activation of MAP kinase activity in the strips, whereas the enzyme activity was not affected in the adventitia. The MAP kinase activation was inhibited by either the angiotensin AT1 receptor antagonist losartan or the endothelin ETA receptor antagonist BQ 123. The combination of both antagonists caused an additive inhibition. The angiotensin AT2 receptor antagonist PD 123,319 and the endothelin ETB receptor antagonist BQ 788 did not affect the MAP kinase activation. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) caused an activation of MAP kinase in the endothelium-intact aorta and the MAP kinase activation was inhibited by losartan or BQ123. The NO releaser nitroprusside inhibited the MAP kinase activation induced by endothelium removal or angiotensin II. These results suggest that even in isolated arteries, NO of endothelial origin tonically exert MAP kinase-inhibiting effects and endogenous angiotensin II and endothelins in the media are tonically released to cause MAP kinase-stimulating effects in medial smooth muscle.

Angiotensin II↗

Evidence for involvement of the lateral parabrachial nucleus in mediation of cholinergic inputs to neurons in the rostral ventrolateral medulla of the rat.

We examined whether sites in the lateral parabrachial nucleus (PBN) where L-glutamate produced increases in arterial pressure were involved in mediation of cholinergic inputs to neurons in the rostral ventrolateral medulla (RVLM). Male Wistar rats were anesthetized, paralyzed and artificially ventilated. Unilateral microinjection of L-glutamate into the lateral PBN produced a pressor response. Microinjection of the muscarinic receptor antagonist scopolamine into the unilateral RVLM inhibited the pressor response to L-glutamate injected ipsilaterally into the lateral PBN, whereas microinjection of the cholinesterase inhibitor physostigmine into the RVLM enhanced it. PBN microinjection of L-glutamate also enhanced the firing rate of RVLM sympathoexcitatory neurons and the enhancement of the firing rate was inhibited by scopolamine iontophoretically applied on neurons. PBN injection of L-glutamate produced a tetrodotoxin (TTX)-sensitive release of ACh in the RVLM. Unilateral microinjection of TTX into the lateral PBN inhibited the pressor response induced by RVLM microinjection of physostigmine. These results provide evidence that neurons in the pressor sites of the lateral PBN are involved in mediation of cholinergic inputs responsible for pressor responses in the RVLM.

Acetylcholine↗

Preferential expression of the gene for a putative inositol 1,4,5-trisphosphate receptor homologue in the mushroom bodies of the brain of the worker honeybee Apis mellifera L.

A gene expressed preferentially in the mushroom bodies of the brain of the worker honeybee Apis mellifera L. was identified by the differential display method and its cDNA was isolated. The cDNA fragment of 534 bp (clone A1) contained an open reading frame encoding 177 amino acid residues having 78, 72, 70, 59 and 55% sequence identities with the inositol 1,4,5-trisphosphate (IP3) receptors of Drosophila melanogaster, Xenopus laevis and humans (types 1, 2 and 3), respectively, suggesting that it encodes a putative IP3 receptor homologue of the honeybee. In situ hybridization revealed that the gene encoding clone A1 was expressed preferentially in the mushroom bodies and not in the optic lobes, antennal lobes and central bodies; in the mushroom body, it was expressed strongly in the large type Kenyon cells and weakly in the small type Kenyon cells. Reverse transcription polymerase chain reaction analysis showed that the gene was expressed strongly in the head and weakly in the antennae, legs, thorax, and abdomen. These results suggest that the A1 gene product plays a crucial role in neural transmission in the mushroom bodies of the worker bee brain.

Amino Acid Sequence↗

DNA ploidy, proliferative activities, and immunophenotype of malignant lymphoma: application of flow cytometry.

BACKGROUND: To explore the flow cytometric diagnosis of malignant lymphoma, we examined the deoxyribonucleic acid (DNA) ploidy, proliferative activities, and immunophenotype of surgical biopsy- and fine-needle aspiration (FNA)-derived materials. Our goal was to determine the possibility of making a diagnosis of malignant lymphoma by flow cytometric analysis of FNA-derived materials. METHODS: The DNA ploidy and proliferative indices including the percentage of S-phase fraction (SPF), G2 + M fraction (G2M), and Ki-67-positive fraction (Ki-67) were analyzed on the fresh materials from 84 consecutive patients with suspected malignant lymphoma. Flow cytometric analysis of surface antigens was simultaneously performed. Fourteen of the patients underwent FNA and subsequent surgical biopsy of the same lymph nodes for flow cytometric analysis. RESULTS: The proliferative indices of intermediate-grade non-Hodgkin's lymphomas (NHL) (n = 28) and high-grade NHL (n = 23) were significantly higher than those of the reactive hyperplasia (n = 25). The total for SPF + G2M of 6% was a satisfactory threshold for differentiating these NHL from reactive hyperplasia (sensitivity of 84%, specificity of 88%, and accuracy of 86%). However, low-grade NHL (n = 3) and Hodgkin's lymphoma (HL, n = 5) could not be discriminated by employing this parameter. DNA aneuploidy was seen in 13 of the 28 intermediate-grade NHL and 8 of the 23 high-grade NHL, whereas it was not seen in 25 reactive hyperplasia, 3 low-grade NHL, and 5 HL. The percentage of CD19-positive cells in B-cell NHL or CD3-positive cells in T-cell NHL was significantly higher compared with those for reactive hyperplasia. The percentage of CD16 + CD56-positive cells in natural killer (NK) cell NHL was extremely high, with a mean of 91.8%. Flow cytometric results for FNA-derived materials showed excellent correlation with those for surgical biopsy-derived specimens. CONCLUSIONS: Analyses of DNA ploidy, proliferative activities, and immunophenotype by flow cytometry (FCM) are useful for diagnosing intermediate- and high-grade NHL. Fine-needle aspiration is a less invasive approach than surgical biopsy, and, when combined with FCM, it may have a place in the diagnosis of NHL.

Biopsy, Needle↗