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Biomedical subjects

T Kubo

Publications and source records attributed to T Kubo.

At least 91 records · Page 5Linked to original sources
PubMed2001

Drastic neuronal loss in vivo by beta-amyloid racemized at Ser(26) residue: conversion of non-toxic [D-Ser(26)]beta-amyloid 1-40 to toxic and proteinase-resistant fragments.

It is unclear how and when insoluble beta-amyloid in senile plaques exerts degenerative effects on distant hippocampal neurons in Alzheimer's disease. Racemization of Ser and Asp residues of insoluble beta-amyloid is a typical age-dependent process. In this study, we investigated the fibril formation activity and cytotoxic activity of beta-amyloid 1-40 racemized at the Asp or Ser residue. In contrast to beta-amyloid 1-40 and its derivative substituted with the D-Asp(1, 7 or 23) or D-Ser(8) residue, [D-Ser(26)]beta-amyloid 1-40 was non-toxic to PC12 cells, and did not exhibit significant fibril formation activity making it soluble. However, [D-Ser(26)]beta-amyloid 1-40, but not beta-amyloid 1-40, was converted in vitro to a potent neurotoxic and truncated peptide, [D-Ser(26)]beta-amyloid 25-35 or [D-Ser(26)]beta-amyloid 25-40, by chymotrypsin-like enzymes and aminopeptidase M. Soluble [D-Ser(26)]beta-amyloid 1-40 was injected into rat hippocampus with a non-toxic dose of ibotenic acid, an excitatory amino acid. Nissl staining and microtubule-associated protein-2 immunostaining revealed that [D-Ser(26)]beta-amyloid 1-40, as well as [D-Ser(26)]beta-amyloid 25-35, produced a drastic degeneration of the CA1 neurons with ibotenic acid although [D-Ser(26)]beta-amyloid 1-40 alone or ibotenic acid alone did not exert neuronal damage. This suggests the in vivo conversion of non-toxic [D-Ser(26)]beta-amyloid 1-40 to the toxic and truncated peptides which enhance the susceptibility of neurons to the excitatory amino acid.These results and the presence of [D-Ser(26)]beta-amyloid 25-35-like antigens in Alzheimer's disease brains suggest that soluble [D-Ser(26)]beta-amyloid 1-40, possibly formed during the aging process, is released from senile plaques, and converted by brain proteinases to truncated [D-Ser(26)]beta-amyloid 25-35(40)-like peptides, which degenerate hippocampal neurons by enhancing the susceptibility to excitatory amino acids in Alzheimer's disease brains. These findings may provide the basis for a new therapeutic approach to prevent the neurodegeneration in Alzheimer's disease.

Alzheimer Disease↗
PubMed2001

Angiotensin receptor blockade in the anterior hypothalamic area inhibits stress-induced pressor responses in rats.

Central angiotensin systems are involved in expression of pressor responses induced by immobilization stress. In this study, we examined whether angiotensin receptors in the anterior hypothalamic area are involved in the pressor response during stress exposure in rats. Intracerebroventricular injections of the angiotensin AT1-receptor antagonist losartan (6.5 and 22 nmol) attenuated pressor responses to immobilization stress dose-dependently. Injections of losartan (0.065 and 0.22 nmol) into the anterior hypothalamic area also suppressed the stress-induced pressor response dose-dependently, whereas intraventricular injection of losartan (2.2 nmol) did not affect it. Immobilization stress caused increases in plasma catecholamine levels. The stress-induced increase of plasma catecholamine levels was also inhibited by angiotensin receptor blockade in the anterior hypothalamic area. The present results suggest that angiotensin receptors in the anterior hypothalamic area are involved in expression of the pressor response and sympathetic activation induced by immobilization stress.

Angiotensin Receptor Antagonists↗
PubMed2001

Early MRI findings of rapidly destructive coxopathy.

To diagnose rapidly destructive coxopathy (RDC) in its early stages and understand the pathomechanism of associated joint destruction, ten cases of RDC were followed by periodic MRI from onset of the disease. In the initial stage (stage 1) of RDC, when radiographs revealed slight narrowing of the joint space, a small subchondral area of low signal intensity was observed on T(1)-weighted images (T1WI) and inhomogeneous high intensity was observed on T(2)-weighted images (T2WI) in the antero-lateral portion of the femoral head. When radiographs showed obliteration of the joint space (stage 2), MRI revealed a diffuse area of low intensity on TIWI and high intensity on T2WI in the proximal femur, including the femoral neck and head, suggesting extensive bone marrow edema. The femoral head and acetabulum were aggressively destroyed (stage 3) in all cases 3 to 6 months after the diffuse abnormal pattern was observed on MRI. MRI in stage 3 cases showed low intensity areas on both T1WI and T2WI. RDC did not show the band-like pattern of low intensity on T1WI and high intensity on T2WI that typify MRI findings in cases of osteonecrosis. When joint space narrowing is observed radiographically, the diffuse abnormal pattern of low intensity on T1WI and high intensity on T2WI induced by a subchondral small lesion might be an early sign of RDC.

Aged↗
PubMed2001

Initial changes of non-traumatic osteonecrosis of femoral head in fat suppression images: bone marrow edema was not found before the appearance of band patterns.

The present study examined initial changes in non-traumatic osteonecrosis of the femoral head (ONF) on T1- and T2-weighted MR images, and fat suppression images. The subjects were 57 renal transplant recipients (37 males and 20 females), whose median age at the time of transplantation was 31.5 years old (range, 10 to 58 years). Twelve patients developed band patterns (sign of established ONF) at an early postoperative period. Among them, 4 joints of 3 patients had a localized, faint signal abnormality in fat suppression images, where band pattern was confirmed later in T1- and T2-weighted images. In all the 57 patients, no bone marrow edema preceding to ONF was observed. Bone marrow edema would not be the cause of ONF in renal transplant patients. Early changes depicted in our fat suppression images would be useful information in the studies on pathogenesis of ONF.

Adult↗
PubMed2001

Hyaluronan suppressed nitric oxide production in the meniscus and synovium of rabbit osteoarthritis model.

Nitric oxide (NO) plays an important role in cartilage degeneration, and NO donors induce meniscus degeneration and synovium inflammation. This study evaluated the effect of intraarticular injections of hyaluronan (HA) on NO production in meniscus and synovium using an experimental osteoarthritis (OA) model. Thirty-six New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT), and were divided into three groups. Four weeks after ACLT, the HA group started to receive intraarticular HA injections once a week for 5 weeks; the vehicle group started to receive the carrier of HA; and the no injection group, no treatment. All ACLT knees were harvested at the 9th week. Meniscus and synovium sections were examined by immunohistochemistry for nitrotyrosine. The pieces of these two tissues were cultured for 24 h. Culture supernatants were analyzed for nitrite concentration. The amount of NO produced by the meniscus was much larger than that produced by the synovium. NO productions in the meniscus and synovium of the HA group were significantly lower than those of the other groups. The results suggest that the inhibition of NO production in meniscus and synovium might be a part of the mechanism of the therapeutic effect of HA on OA.

Animals↗
PubMed2001

Sympathetic skin response evoked by respiratory stimulation as a measure of sympathetic function.

OBJECTIVES: To compare respiratory and electrical methods of evoking a sympathetic skin response (SSR). METHODS: SSRs evoked by both electrical and respiratory stimulation were recorded from the palms of 47 healthy volunteers. Expiration and inspiration were used as separate stimuli. The correlation coefficients between the amplitude and latency of the SSR from the palm electrodes and the various components of heart rate variability were calculated. RESULTS: Waveform patterns of the SSRs obtained from electrical stimulation showed varied responses to and habituation to this type of stimulation. On the other hand, no subjects showed a phase change in SSR waveform patterns between the first and last expiratory stimuli. The potentials recorded after expiratory stimulation had significantly greater amplitudes than those recorded after electrical stimuli. The low frequency component of heart rate variability induced by expiratory stimulation was significantly greater than that induced by electrical stimulation. The SSR may also correlate strongly with the change of respiratory rate since a more rapid pressure change occurs during expiratory movement than during inspiratory movements. CONCLUSIONS: The SSR evoked by expiratory stimulation is more reliable than either electrical stimulation or inspiratory stimulation for determining sympathetic function.

Adult↗
PubMed2001

Highly efficient gene transfer into murine liver achieved by intravenous administration of naked Epstein-Barr virus (EBV)-based plasmid vectors.

Naked plasmid DNA (pDNA) injection could become an alternative procedure to viral and nonviral gene delivery systems. We have previously shown that Epstein-Barr virus (EBV)-based plasmid vectors containing the EBV nuclear antigen 1 (EBNA1) gene and the oriP sequence enable quite high and long-lasting expression in various in vitro and in vivo transfection systems. The EBV-based plasmids were intravenously injected into mice via their tail vein under high pressure. A large amount of the marker gene product was expressed in the liver; as much as 320 microg of luciferase was demonstrated per gram of liver at 8 to 24 h after a single injection with 10 microg of DNA. More than 70% of liver cells stained with X-gal when beta-gal gene was transferred. The expression level was significantly higher than that obtained by conventional pDNA lacking the EBNA1 gene and oriP. On day 35 after the transfection, the expression from the EBV-based plasmid was approximately 100-fold stronger than the conventional pDNA gene expression. Both the EBNA1 gene and oriP are a prerequisite for the augmentation of the transfection efficiency. These results suggest that the intravascular transfection with naked EBV-based plasmid may provide a quite efficient, simple and convenient means to transduce therapeutic genes in vivo into the liver.

Animals↗
PubMed2001

Identification of a novel gene, Mblk-1, that encodes a putative transcription factor expressed preferentially in the large-type Kenyon cells of the honeybee brain.

Mushroom bodies (MBs) are considered to be involved in higher-order sensory processing in the insect brain. To identify the genes involved in the intrinsic function of the honeybee MBs, we searched for genes preferentially expressed therein, using the differential display method. Here we report a novel gene encoding a putative transcription factor (Mblk-1) expressed preferentially in one of two types of intrinsic MB neurones, the large-type Kenyon cells, which makes Mblk-1 a candidate gene involved in the advanced behaviours of honeybees. A putative DNA binding motif of Mblk-1 had significant sequence homology with those encoded by genes from various animal species, suggesting that the functions of these proteins in neural cells are conserved among the animal kingdom.

Amino Acid Sequence↗
PubMed2001

An ultrasensitive assay revealed age-related changes in serum oestradiol at low concentrations in both sexes from infancy to puberty.

OBJECTIVE: Intensive studies of oestrogen receptors have suggested extragonadal functions of oestrogen. However, the in vivo extragonadal functions of oestradiol remain unclear because of the lack of an adequate assay system at low concentrations. In this study, we assessed the usefulness of a new ultra-sensitive assay for children. METHODS: Serum oestradiol was measured with an ultrasensitive assay (assayable concentration: 5-1,835 pmol/l: ESTR-US-CT, CIS biointernational, France). Intra- and interassay coefficients of variation at low concentrations (< 36.7 pmol/l) were 8.2 +/- 6.8 (0.1-31.2)% and 8.3 +/- 3.7 (7.5-12.9)%, respectively. SUBJECTS: Sera from 88 healthy children (55 males and 33 females; 1 month to 16 years old) and 31 patients who underwent gonadal suppression therapy were analysed. RESULTS: Age-related changes were observed in both sexes. Serum oestradiol concentrations in childhood decreased slightly compared to those in infancy, then increased at puberty. Most prepubertal children showed oestradiol concentrations lower than 36.7 pmol/l. A study on patients who underwent gonadal suppression therapy revealed oestradiol changes within low concentrations, depending on the stage of the therapy. CONCLUSIONS: The new assay was considered precise enough for the assessment of oestradiol secretion at low concentrations in childhood. Age-related changes in serum oestradiol suggested gonadal activity in the prepubertal period. This assay could be a powerful tool for investigating novel oestradiol functions in vivo.

Adolescent↗
PubMed2001

Photoconductive imaging in a photon scanning tunnelling microscope capable of point-contact current sensing using a conductive fibre probe.

A photoconductive photon scanning tunnelling microscope was developed to investigate the point-contact photoconductive properties of condensed matter. In order to detect the current and the optical signal at a local point on a surface, we coated the edge of a bent type fibre probe with indium tin oxide. Thus it was possible to measure both photocurrent and optical property with subwavelength resolution. The performance of the novel microscope was evaluated by analysing an organic thin film of copper phthalocyanine (CuPc), which is known to be an efficient photoconductive material. Photocurrent and current-voltage characteristics were observed at the local point on the CuPc thin films. Furthermore, photoconductive images were obtained with topography and near-field optical imaging using this system. The photoconductive PSTM shows potential in various areas of future optics and electronics.

Journal Article↗
PubMed2001

Activation of the Sarcophaga lectin gene promoter by (A + T)-stretch binding protein.

Previously, we purified and isolated a cDNA for (A + T)-stretch binding protein (ATBP) that binds to (A + T)-stretches in the 5' upstream region of the Sarcophaga lectin gene [Nakanishi-Matsui, M., Kubo, T. & Natori, S. (1995) Eur. J. Biochem. 230, 396-400]. Here, we used a luciferase reporter to examine the effect of ATBP on transcription of the Sarcophaga lectin gene. Deletion experiments revealed that ATBP activates the Sarcophaga lectin gene in a 5' upstream sequence-dependent manner, and that at least the N-terminal 25 residues, the three Zn-finger domains, an acidic domain and the third hydrophobic domain of ATBP are indispensable for its function. Furthermore, a synergistic effect was detected between ATBP and Dif, suggesting that ATBP is involved in the activation of insect immunity genes.

Animals↗
PubMed2001

Developmental changes in the mRNA levels of IGF-I and its related genes in the reproductive organs of Japanese quail (Coturnix coturnix japonica).

Summary Insulin-like growth factor-I (IGF-I) is involved in the regulation of growth and differentiation of a variety of vertebrate tissues. The biological actions of IGF-I are mediated mainly by the IGF-I receptor (IGF-IR) and partly by the insulin receptor (IR) and modulated by IGF binding proteins (IGFBP). We conducted studies designed to clarify the possible roles of IGF system in the development of the avian reproductive organs. We cloned cDNAs of IGF-I, IGF-IR, IR and IGFBP-2 of Japanese quail and simultaneously measured the expression of these genes in the quail liver, testis and oviduct at different ages using a lysate RNase protection assay. Hepatic IGF-I mRNA levels increased rapidly and remained elevated during the rapid-growing period, which coincided with the period of rapid increase in testicular weight. IGF-I mRNA was detected at each stage of developing testis examined. Its level was high at the early stage and decreased with age. IGFBP-2 mRNA in testis exhibited a similar expression pattern to that of IGF-I, whereas a divergence in IGF-I and IGF-IR gene expression was observed. Both IGF-IR and IR mRNAs increased when the testis grew rapidly and decreased when sexual maturation was almost completed. These results suggest that IGF-I may serve as an autocrine/paracrine regulator as well as an endocrine regulator in the testicular development and function of Japanese quail. In the oviduct, IGF-I, IGF-IR, IR and IGFBP-2 mRNAs were also developmentally regulated. A rapid growth of the oviduct was accompanied by a significant increase in the level of IGF-I mRNA. The expression of genes encoding IGF-IR, IR and IGFBP-2 in the oviduct exhibited a similar developmental change to that of IGF-I. These results suggest that IGF-I mainly works in an autocrine and/or paracrine manner in the oviduct during the development of this organ. The findings of the present study provide further evidence of an important role for IGF system in the development and function of the avian reproductive system.

Animals↗
PubMed2001

Cementless Lord total hip arthroplasty: cup loosening common after minimum 10-year follow-up of 103 hips.

We evaluated the clinical and radiographic results of 103 (88 patients) cementless Lord total hip arthroplasty after a mean follow-up period of 12.5 (10-16) years. 77 hips had arthrosis, 15 rheumatoid arthritis and 11 osteonecrosis. The preoperative mean Harris Hip Score improved from 47 (19-66) to 87 (62-99) at 5 years, but declined to 77 (56-97) at the final examination. The survivorship of the cup, using radiographically confirmed aseptic loosening as the end point, was 63% at 10 years and 45% at 15 years and the survivorship of the stem was 97% at 10 years and 96% at 15 years. The low figures of the cup may be due to insufficient contact between the smooth-surfaced threads of the cup and the acetabular bone. Thinner polyethylene, insufficient initial bone coverage, and larger femoral head diameter were significantly related to the occurrence of loosening. We can not recommend this smooth-surfaced threaded cup because of its high failure.

Adult↗
PubMed2001

Significance of auditory evoked responses (EABR and P300) in cochlear implant subjects.

An electrically derived auditory brainstem response (EABR) was recorded intra-operatively, and the event-related potential (P300) postoperatively in post-lingually deaf adult cochlear implantees. EABR and P300 were recorded from two groups of 25 subjects each. All subjects had a cochlear mini-22 system implanted at our center between 1994 and 1998. Two parameters of EABR, threshold (T) and the gradient of the amplitude-growth (AG) curve, were used for correlation with postoperative speech reception scores. The consonant recognition score (CRS) measured 1 month postoperatively showed a significant correlation with the AG curve of EABR (Spearman rank order test, p = 0.004), but not at later points in time. No correlation was found between the T and CRS at any time postoperatively. As the AG curve reflects the number of remaining spiral ganglion cells in the inner ear, a large number of surviving neurons is thought to be advantageous only for initial speech learning. The latency of P300 was measured for correlation with the speech reception score. The division of the cochlear implant subjects into a fair and a good hearing group according to their CRS showed that the average latency of P300 was significantly longer for the fair hearing group than for the good hearing group. A follow-up study showed that P300 latency significantly correlated with CRS measured at 6 months, 1 year and at a later time. As the latency of P300 is thought to reflect the time for sound processing in the central auditory system, our results indicate that plasticity of the central auditory system is more important than that of the peripheral auditory system for speech learning in cochlear implant subjects.

Adult↗
PubMed2001

Noradrenergic pathways involved in the development of vertigo and dizziness--a review.

In this study, vestibular caloric stimulation (CS) inhibited noradrenergic (NA) neurons of the locus coeruleus (LC) in rats. The vestibular input can be modified by the ventrolateral medulla (VLM), which then inhibits the LC neuronal activity via GABAA receptors. Clinically, CS induces vertigo in humans. Thus, LC-NA inhibition may be involved in the development of vertigo. Moreover, it is speculated that Sopite syndrome, one of the major symptom complexes of motion sickness, is also evoked by LC-NA inhibition. The central LC-NA neuronal system may participate in vertigo and motion sickness independent of the histaminergic neuronal system. In contrast, the cholinergic neuronal system may mediate LC-NA inhibition during the vestibulo-atonomic reflex. The LC-NA system projects to most higher centers and affects sensory information processing. Therefore, it is suggested that the suppression of sensory information processing induced by LC-NA inhibition causes drowsiness, one of the major symptoms of vertigo and motion sickness. It is also speculated that LC-NA inhibition participates in the development of sensory mismatch during vertigo and motion sickness.

Animals↗
PubMed2001

Role of cholinergic mossy fibers in vestibular nuclei in the development of vestibular compensation.

Several lines of evidence have suggested that acetylcholine is a possible neurotransmitter/neuromodulator involved in vestibular compensation. However, details of cholinergic effective sites during vestibular compensation remain unclear. In this study, we selectively damaged the rat vestibulo-floccular cholinergic mossy fibers using ethylcholine mustard aziridinium ion. In these animals, unilateral labyrinthectomy caused more severe vestibulo-ocular deficits, especially in the initial stage. These findings suggest that the vestibulo-floccular cholinergic mossy fibers serve to restore the balance between intervestibular nuclear activities in order to induce vestibular compensation in the initial stage.

Animals↗