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Biomedical subjects

T Kubo

Publications and source records attributed to T Kubo.

At least 343 records · Page 19Linked to original sources
PubMed1998

Evidence suggesting that lateral parabrachial nucleus is responsible for enhanced medullary cholinergic activity in hypertension.

Cholinergic activities in the rostral ventrolateral medulla are enhanced in hypertensive animals, and enhanced cholinergic activity contributes to hypertension. Neurons in the lateral parabrachial nucleus and baroreceptors are suggested to be involved in mediation of acetylcholine release in the rostral ventrolateral medulla. To investigate the hypothesis that the lateral parabrachial nucleus is involved in the increased medullary cholinergic activity in hypertensive rats, we measured choline acetyltransferase activity in the rostral ventrolateral medulla, and examined effects of electrolytic lesioning of the lateral parabrachial nucleus in deoxycorticosterone acetate-salt hypertensive rats. We found that choline acetyl-transferase activity in the medullary region was increased in deoxycorticosterone acetate-salt hypertensive rats. Unilateral lesioning of the lateral parabrachial nucleus abolished the increase in choline acetyltransferase activity in the lesioned side of the medullary region of hypertensive rats, whereas such activity in the medullary region of control rats was unaffected by lesioning. Bilateral lesioning of the lateral parabrachial nucleus inhibited the development of hypertension in hypertensive rats. In contrast, baroreceptor denervation did not inhibit the increase in choline acetyltransferase activity in the medullary region of hypertensive rats. These results are compatible with the hypothesis that the lateral parabrachial nucleus area is involved in mediation of increased medullary cholinergic activity and thus plays a role in the development of hypertension.

Animals↗
PubMed1998

L-type calcium channels in vascular smooth muscle cells from spontaneously hypertensive rats: effects of calcium agonist and antagonist.

Studies using the whole-cell voltage-clamp technique have demonstrated that L-type Ca2+ channel activity is increased in vascular smooth muscle cells from spontaneously hypertensive rats (SHR). We recorded L-type Ca2+ channel currents in cultured mesenteric artery smooth muscle cells from SHR and Wistar Kyoto (WKY) rats by using the cell-attached patch-clamp technique. Depolarizing voltage steps from a holding potential of -40 mV elicited voltage-dependent inward Ba2+ currents. There was no difference in the L-type Ca2+ channel I-V curve or in the open probability between SHR and WKY. The inward currents were inhibited by the Ca2+ antagonists nifedipine and verapamil, but were enhanced by the Ca2+ agonist Bay K 8644 in a concentration-dependent manner. The Bay K 8644-induced increase and the nifedipine-induced inhibition of the inward currents were enhanced in SHR, whereas there was no difference in the verapamil-induced inhibition of the currents between the two strains of rats. These results suggest that the enhanced L-type Ca2+ channel activity observed in vascular smooth muscle cells from SHR is not due to altered function of a single L-type Ca2+ channel. It appears that the sensitivity of dihydropyridine receptors in the channels is enhanced in SHR.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Effect of growth hormone therapy in children with achondroplasia: growth pattern, hypothalamic-pituitary function, and genotype.

OBJECTIVE: Although there are a few reports on GH therapy in achondroplasia, these were based on a small sample and/or short-term observation. To clarify the effectiveness of GH treatment on short stature in achondroplasia and hypochondroplasia, a long-term treatment study in a larger number of patients was performed. METHOD: Forty-two children (16 males and 26 females, age 3-14 years) with achondroplasia were examined in this study. Initially, we evaluated hypothalamic-pituitary function and point mutation analysis as previously reported. After the evaluation, the children were treated with GH for more than 2 years; then post-treatment growth velocity and body proportion parameters were determined. RESULTS: The 35 typical variants of our achondroplasia patients showed previously reported point mutation in the fibroblast growth factor receptor 3 gene. The annual height gain during GH therapy was significantly greater than that before therapy (3.9 +/- 1.0 cm/year before treatment vs 6.5 +/- 1.8 cm/year for the first year and 4.6 +/- 1.6 cm/year for the second year of treatment). The body disproportion had not been aggravated during the treatment period. CONCLUSION: We conclude that GH might be beneficial in the treatment of short stature in children with achondroplasia in the first 2 years of treatment.

Achondroplasia↗
PubMed1998

Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on progestin biosynthesis in cultured granulosa cells from rat ovary and expression of mRNA encoding PACAP type IA receptor.

The purpose of this study was to detect the presence of mRNA encoding pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptor in granulosa cells from rat ovary and to examine the effect of PACAP on progestin biosynthesis. mRNA was isolated from granulosa cells from the ovaries of immature rats treated with pregnant mares' serum gonadotrophin. The technique of reverse transcription and polymerase chain reaction with primers specific to PACAP type I receptor were used to demonstrate the expression of mRNA encoding PACAP type IA receptor in these cells. Granulosa cells were also cultured in the absence or presence of 100 ng LH ml-1 with various doses of PACAP-38 (10, 100 and 1000 ng ml-1). At the end of the incubation period, the incubation media were collected and concentrations of progesterone, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) and cAMP were measured. Increasing concentrations of PACAP-38 significantly stimulated the production of progestins (progesterone and 20 alpha-OH-P) and cAMP accumulation in a dose-dependent manner (P < 0.01; ANOVA). This effect was observed in media cultured for 24 and 48 h in both basal and LH-stimulated states. PACAP-38 did not significantly affect the ratio of progesterone: 20 alpha-OH-P produced by granulosa cells cultured for 24 h in the LH-stimulated state. However, at 1000 ng ml-1, PACAP-38 significantly decreased the ratio of progesterone to 20 alpha-OH-P production in granulosa cells cultured for 48 h (P < 0.01). These results suggest that granulosa cells from rat ovary express mRNA encoding PACAP type IA receptor and that PACAP may regulate granulosa cell differentiation and play an important role in the reproductive process.

Analysis of Variance↗
PubMed1998

Effect of growth hormone releasing hormone on luteinizing hormone stimulated progestin biosynthesis in cultured rat ovarian granulosa cells.

In the present study, we examined the effects of growth hormone releasing hormone (GHRH) on luteinizing hormone (LH)-stimulated progestin biosynthesis. Granulosa cells from pregnant mare serum gonadotropin (PMSG)-treated immature rats were cultured in vitro in the absence or presence of ovine. National Institute of Health LH (100 ng/ml) with various doses of GHRH (10(-9), 10(-8) and 10(-7) mol/l) for 24 h. At the end of the incubation period, the incubation media were collected and levels of progesterone, 20 alpha-hydroxypregn-4-en-3-one and cyclic adenosine 3',5'-monophosphate (cAMP) were measured. GHRH significantly stimulated progesterone production and cAMP accumulation in media in a dose-dependent manner in the basal state (p < 0.01 and p < 0.001, respectively). In the presence of LH, GHRH significantly inhibited LH-stimulated progesterone production in a dose-dependent manner (p < 0.01), whereas increasing concentrations of GHRH produced progressive increases in cAMP accumulation (p < 0.05). Since increasing concentrations of GHRH produced progressive decreases in the ratio of progesterone to 20 alpha-hydroxypregn-4-en-3-one production in the LH-stimulated state (p < 0.01), GHRH may be involved in modulation of key steroidogenic steps concerned with progesterone degradation rather than formation in LH-stimulated rat granulosa cells. These results suggest that GHRH may regulate the effects of LH in granulosa cells and play an important role in the reproductive process.

Analysis of Variance↗
PubMed1998

Baroreceptor activation causes release of acetylcholine in the rostral ventrolateral medulla of the rat.

We examined whether baroreceptor activation causes a release of acetylcholine (ACh) in the rostral ventrolateral medulla (RVLM) of the rat, in order to investigate a possible connection between RVLM cholinergic systems and cardiovascular baroreflexes. Male Wistar rats were anesthetized, paralyzed and artificially ventilated. Either electrical stimulation of aortic nerve or baroreceptor activation by intravenous phenylephrine produced an increase of the release of ACh in the RVLM, whereas baroreceptor denervation and tetrodotoxin (TTX) microinfusion in the RVLM inhibited the increase in ACh release induced by phenylephrine. TTX injected in the caudal ventrolateral medulla (CVLM) inhibited the phenylephrine-induced increase of ACh release. The excitatory amino acid L-glutamate microinfused in the CVLM produced an release in ACh release in the RVLM. These results suggest that there is a connection between RVLM cholinergic systems and cardiovascular baroreflexes. It is probable that neurons in the CVLM are involved in mediating the release of ACh in the RVLM.

Acetylcholine↗
PubMed1998

MRI evaluation of the inferior glenohumeral ligament. Comparison with arthroscopic findings in 81 shoulders.

Arthroscopic Bankart repair, using staples, requires a thick and wide anterior band of the inferior glenohumeral ligament. We compared MRI and arthroscopic findings of the ligament in 81 shoulders with traumatic anterior glenohumeral instability. When fluid was present in the shoulder, sensitivity and specificity of the MRI evaluation for the presence of a thick and wide ligament were 82% and 100%, respectively. In shoulders without joint fluid, the condition of the ligament was evaluated according to the presence of a low- or moderate-signal triangle structure on the anterior margin of the glenoid cavity in the 3 MR images obtained from the inferior 2 cm of the glenoid. Sensitivity and specificity of the MRI evaluation in cases without fluid were 84% and 93%, respectively. The MR technique needs to be further improved to achieve better sensitivity for preoperative selection of shoulders suitable for Bankart repair with staples.

Adolescent↗
PubMed1998

[Clinical significance of electrically evoked auditory brainstem response].

Electrically evoked auditory brainstem responses (EABR) were recorded in 31 postlingually deafened adults, who had recently received cochlear implants (mini-system, Cochlear Ltd). The wave consisted of three distinct positive peaks labeled P1, P2, and P3 with latency of 1.35 (+/- 0.14), 2.17 (+/- 0.18) and 4.08 (+/- 0.31) ms, respectively. The P3 threshold (EABR-T) and slope (EABR-S) were 0.9 (+/- 0.47) mA and 0.6 (+/- 0.28) muv/mA, respectively. The relationships between the EABR parameters (EABR T and -S of the P3 wave) and age, duration of deafness, promontory test and subjective response (T and C-level) were investigated. The scattergram showed a strong negative linear relationship between EABR-S and subjective T-level. This finding suggests that EABR-S is good measure of postoperative perception.

Adult↗
PubMed1998

[Flow cytometric DNA analysis and MR imaging of salivary gland tumors].

We correlated the histopathology of 32 cases of salivary gland tumors with MR imaging and flow cytometric DNA analysis. All malignant tumors were invasive and/or had an ill-defined margin. Fifty-seven percent of the pleomorphic adenomas were shown as a high signal intensity area on T2 weighted images. Fifty-six percent of Warthin tumors were shown as a low or iso signal intensity area on T2 weighted images associated with the cystic portion. Sixty-seven percent of malignant tumors were characterized by DNA aneuploidy and/or a total percentage of the S-phase fraction plus the G2 + M fraction higher than 10%. It was less than 10% and the Ki-67 positive fraction was higher than 20% in all pleomorphic adenomas. The Ki-67 positive fraction was less than 20% in 78% of Warthin tumors. The histopathology of all malignant tumors, 86% of the pleomorphic adenomas, and 89% of Warthin tumors was correctly predicted by the combination of MR images and flow cytometry. We suggest that the MR images combined with flow cytometric analysis of fine needle aspiration-derived materials is useful in the pre-operative histopathologic diagnosis of salivary gland tumors.

Adenolymphoma↗
PubMed1998

[Identification of vestibular compensation-associated molecules by means of differential display].

The differential display method was used to identify gene expression which is altered in the cerebellar flocculus after unilateral labyrinthectomy (UL). Total RNA from flocculi of sham-operated and labyrinthectomized rats was isolated, amplified by PCR using arbitrary primer sets and separated by electrophoresis on a polyacrylamide gel. PCR products, whose amounts were significantly different in samples from labyrinthectomized animals and those from controls, were cut out of the gel and sequenced. One of the up-regulated products was the rat protein phosphatase 2A beta catalytic subunit mRNA and one of the down-regulated products was the rat glutamate receptor delta-2 subunit mRNA. Histochemical examination of in situ hybridization showed that those molecules were intensively localized in the Purkinje cell layer. In labyrinthectomized rats, UL-induced nystagmus gradually disappeared within 3 days after UL. These findings suggest that changes in expression of those molecules in the floccular Purkinje cells after UL is involved in vestibular compensation. So far various kinds of neural plasticity-associated molecules have been investigated, mainly by slice-in vitro studies. This study indicates that differential display is a feasible molecular biological in vivo method for investigation of the mechanism of neural plasticity.

Animals↗
PubMed1998

[Apoptosis-inducing and -preventing signal transduction pathways in cultured cerebellar granule neurons].

1. Cultured cerebellar granule neurons maintained in medium containing 26 mM potassium (high K+ or HK+) undergo cell death when switched to medium with 5 mM potassium (low K+ or LK+). This low K(+)-induced cell death has typical features of apoptosis. The intracellular signaling pathway of low K(+)-induced apoptosis has been investigated. 2. Cerebellar granule neurons become committed to undergo apoptosis between 2 and 5 h after K+ deprivation, judging from the inability of high K+ to rescue them after this time. Although the levels of most mRNAs decrease markedly concomitant with commitment, expression of c-jun mRNA increases 2-3 h after K+ deprivation. Among the family of caspases, a caspase-3-like protease is activated within 4 h of lowering the K+ concentration. A caspase-1-like protease is also activated within 2 h of K+ deprivation. 3. Inhibition of phosphatidylinositol 3-kinase (PI3-K) activity by LY294002 or wortmannin also induces apoptosis in cerebellar granule neurons. The intracellular signaling pathway of LY294002-induced apoptosis has been investigated. The activity of c-Jun N-terminal kinase (JNK) increases 8 h after addition of LY294002 to high K+ medium or low K+ medium containing BDNF. Expression of c-Jun protein also increases almost simultaneously. 4. The low K(+)-induced apoptosis of cerebellar granule neurons is prevented by high K+ (membrane depolarization by high K+), BDNF, IGF-1, bFGF or cAMP. The intracellular signaling pathways by which these agents prevent low K(+)-induced apoptosis have been investigated. Agents other than cAMP prevent apoptosis through PI3-K and a Ser/Thr kinase, Akt/PKB. The survival-promoting effect of cAMP does not depend on the PI3-K-Akt pathway.

Apoptosis↗
PubMed1998

Molecular mechanisms of vestibular compensation in the central vestibular system--review.

Vestibular compensation consists of two stages: the inhibition of the contralesional medial vestibular nucleus (contra-MVe) activities at the acute stage after unilateral labyrinthectomy (UL) and the recovery and maintenance of the ipsilesional MVe (ipsi-MVe) spontaneous activities at the chronic stage after UL. In this paper, we reviewed molecular mechanisms of vestibular compensation in the central vestibular system using several morphological and pharmacological approaches in rats. Based on our examinations, we propose the following hypotheses: i) at the acute stage after UL, the activated neurons in the ipsi-MVe project their axons into the flocculus to inhibit the contra-MVe neurons via the NMDA receptor, nitric oxide (NO) and/or GABA-mediated signalling, resulting in the restoration of balance between intervestibular nuclear activities. ii) At the chronic stage after UL, the flocculus depresses the inhibitory effects on the ipsi-MVe neurons via protein phosphatase 2A (PP2A) beta, protein kinase C (PKC) and glutamate receptor (GluR) delta-2, to help the recovery and maintenance of ipsi-MVe activities.

Animals↗
PubMed1998

[Radiation therapy for non-small cell lung cancer with postoperative intrathoracic recurrence].

We reviewed patients with intrathoracic recurrence of non-small cell lung cancer after surgery, with reference to the feasibility of radiotherapy. The series consisted of 46 patients (39 males and 7 females) treated by radiotherapy from 1982 to 1995. Histology included squamous cell carcinoma (28 patients), adenocarcinoma (17), and large cell carcinoma (1). Clinical stage by UICC classification (1987) was as follows: stage I(2 patients), stage II(1), stage IIIa(13), stage IIIb(23), and stage IV(7). Recurrences were noted in bronchial stump (18 patients) and surgical scar (4). Metastases occurred in hilar-mediastinal lymphnodes (15), lung fields (7), and pleuropericardium (2). The mean interval from surgery to recurrence was 27 months. Delivered dose ranged from 45 to 80 Gy, and 19 patients received combined chemotherapy. Therapeutic results were as follows: complete response in 16 patients, partial response in 27, no response in 12 and progressive disease in 1, Overall 2- and 5-year survival rates were 17% and 11%, respectively, and 10 months in MST. On univariate analysis, significant prognostic factors were sex, stage at recurrence, recurrence pattern, performance status and initial response to radiotherapy, while multivariate analysis showed sex and initial response. From these data, we are encouraged by effective radiotherapy for postoperative intrathoracic recurrence of non-small cell lung cancer, especially in patients with stump or lymphnode recurrence.

Adenocarcinoma↗
PubMed1998

[Precipitating factors in patients with repetitive exacerbation of chronic left heart failure].

The precipitating factors of repetitive exacerbation were investigated in 110 consecutive patients with chronic left heart failure admitted due to acute exacerbation more than twice to the medical emergency ward of National Cardiovascular Center from January, 1992 to December, 1996. The controls were 189 consecutive patients with chronic left heart failure admitted to the ward due to acute exacerbation only once during the same period. Excessive intake of water or sodium, overwork and infection were common precipitating factors in the first decompensation of left heart failure, but the former two factors became less common with repeated admission. Patient mistakes such as excessive intake of water or sodium, overwork and noncompliance with medications, and new onset arrhythmias were common precipitating factors in patients (n = 13) admitted to the ward more than four times. Infection was a common precipitating factor (63%) in patients with a time interval between readmission and the last discharge of longer than 2 years. Despite repeated admission, infection was a common precipitating factor in patients with valvular heart disease (n = 31), patient mistakes were common in heart disease with left ventricular hypertrophy (n = 20), and infection and new onset arrhythmias were common in dilated cardiomyopathy (n = 28) and old myocardial infarction (n = 31). Patient mistakes and new onset arrhythmias were the common factors that led to repetitive exacerbation of left heart failure, and precipitating factors were characterized by the etiology of left heart failure.

Aged↗
PubMed1998

Adenovirus mediated gene delivery to the joints of guinea pigs.

OBJECTIVE: To clarify in vivo applicability of adenovirus mediated gene delivery to examine a gene therapy for human joint diseases. METHODS: We directly injected vectors harbouring beta-galactosidase gene and transforming growth factor (TGF)-beta1 gene into the joints of Hartley guinea pigs. Expressions of delivered LacZ were examined by 5-bromo-4-chloro-3-indolyl-beta-D-galactoside staining and reverse transcription-polymerase chain reaction. The levels of TGF-beta1 that were delivered to the joint and then transferred to the joint fluid were assessed by ELISA. RESULTS: LacZ expression was observed in almost all synovial tissue samples and in chondrocytes on the surface of degenerated cartilage. In the other organs, expression of delivered genes was not observed. For 2 weeks following gene delivery TGF-beta1 levels in joint fluid were significantly higher than the levels in the controls for 2 weeks. CONCLUSION: Direct gene delivery into the joint cavity is feasible with the in vivo gene delivery method using adenovirus vector and would be clinically applicable.

Adenoviridae↗
PubMed1998

Histomorphometric and biochemical effect of various hyaluronans on early osteoarthritis.

OBJECTIVE: To evaluate, histomorphometrically and biochemically, different protective effects of clinically used hyaluronans (HA). METHODS: An experimental osteoarthritis (OA) model was applied to 132 mature NZW rabbits by resecting the unilateral anterior cruciate ligament (ACL). The other knee, where ACL remained intact, served as the control. We used native HA with different molecular weights, HA-50 (MW 5-7.3 x 10(5)), HA-80 (MW 8 x 10(5)), HA-360 (MW 3.6 x 10(6)), and crosslinked HA (HA-CL). HA were injected into the joint once a week for 5 weeks (HA-50, HA-80, HA-360) or 3 weeks (HA-CL) beginning 4 weeks after ACL transection. Histomorphometric and biochemical assessment was performed 9 weeks post-transection for both the HA treated and nontreated groups. RESULTS: In gross morphological observation, cartilage degeneration was suppressed in HA treated groups, and this effect was superior in the groups receiving either HA-80 or HA-CL. Histomorphometric and biochemical analyses of the articular cartilage revealed similar results: the HA-80 and HA-CL groups showed no significant differences between the ACL transection and the control knees by histomorphometric variables, while the nontreated groups revealed significant degeneration. These evaluations were done in unblinded fashion. Biochemical analyses, including DNA synthesis in the synovium, also showed that articular cartilage and synovium in the HA-80 and HA-CL groups did not present significant changes compared to controls. CONCLUSION: In quantitative evaluation of this short term study using the OA model, native HA-80 and HA-CL presented a superior cartilage protective effect compared to the other native HA.

Animals↗
PubMed1998

[A case of pure agraphia due to left parietal lobe infarction].

We reported a case of a 63-year-old right handed man with pure agraphia due to the left parietal lobe infarction. The characteristics of agraphia in the patient were as follows. 1) The written letters were generally recognizable and well formed. 2) He succeeded in pointing to single Kana letter named by the examiner from the Japanese syllabary, but missed in pointing to Kana words. 3) Further, it took more time for the patient to point to even single Kana letter than for the control. 4) Most errors in Kana writing was substitution. Errors in Kanji writing are partial lacking or no response. But his ability in Kanji writing was facilitated by visual cues. He was unable to describe the Hen (a left-hand radical) and Tsukuri (the body) of some Kanji letters and to name some Kanji letters when their Hen and Tsukuri were orally given. We classified pure agraphia into two types out of some references. In one type (Type 1), letters in writing are poorly formed, but the ability to make words with the methods other than writing, for example spelling with anagrams or typing are preserved. In another type (Type 2), letters in writing were well-formed, but spelling with anagrams or typing were abnormal. Type 1 agraphia could result from the only deficit of graphic motor engram, while type 2 agraphia could be caused by the deficits other than graphic motor engram. Agraphia in this case belongs to the type 2. The features of agraphia in this case suggested that his agraphia was caused by a disorder in recalling graphemes of letters, and in arranging at least of Kana-letters.

Agraphia↗