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Biomedical subjects

T Kubo

Publications and source records attributed to T Kubo.

At least 379 records · Page 21Linked to original sources

Role of the flocculus in the development of vestibular compensation: immunohistochemical studies with retrograde tracing and flocculectomy using Fos expression as a marker in the rat brainstem.

After unilateral labyrinthectomy in rats, Fos-like immunoreactive neurons appeared in the ipsilateral medial vestibular nucleus, contralateral prepositus hypoglossal nucleus and contralateral inferior olive beta subnucleus. and thereafter gradually disappeared in accordance with the development of vestibular compensation. This finding indicated that the activation of these nuclei is the initial event of vestibular compensation. In the present study, retrograde tracing experiments revealed that these Fos-like immunoreactive neurons project a proportion of their axons to the vestibulocerebellum (uvula-nodulus, flocculus). Before vestibular compensation was accomplished, right, left or bilateral flocculectomy was performed in right-labyrinthectomized rats. All these treatments caused reappearance of unilateral labyrinthectomy-induced behavioral deficits and Fos expression in the left medial vestibular nucleus and right prepositus hypoglossal nucleus. Since floccular efferents are GABAergic, these results indicate that the neurons in which Fos expression was detected by flocculectomy had been inhibited after unilateral labyrinthectomy by floccular Purkinje neurons and that disinhibition of these neurons induced by flocculectomy caused decompensation. Based on our present findings, we propose a hypothesis that the bilateral flocculus serves the restoration of balance between intervestibular nuclear activities to induce vestibular compensation after unilateral labyrinthectomy.

Animals↗

Neurons in rostral ventrolateral medulla mediate vestibular inhibition of locus coeruleus in rats.

The effects of caloric vestibular stimulation on the central noradrenergic neurons system were examined in the rat. In urethane-anesthetized rats, caloric stimulation inhibited the spontaneous activity of noradrenergic locus coeruleus neurons and increased systemic blood pressure. Electrical and chemical lesions in the ventrolateral medulla attenuated both the locus coeruleus inhibition and the blood pressure increase in response to caloric stimulation. Neither the neuronal inhibition nor the pressor effect was attenuated by any deafferentation of the forebrain or baroreceptors, or lesioning of the nucleus tractus solitarius. These findings indicate that the caloric stimulation-induced locus coeruleus inhibition is mediated by neurons in the ventrolateral medulla, and that these neurons also mediate the vestibulo-pressor responses. The locus coeruleus inhibition via the ventrolateral medulla is, however, considered to be independent of ventrolateral medulla-mediated systemic pressor effect. Collectively these findings suggest that the ventrolateral medulla is the major origin of inhibitory vestibular input to the noradrenergic neurons of the locus coeruleus, and that the ventrolateral medulla plays an important role in the vestibulo-autonomic response.

Animals↗

Cholinergic mechanisms responsible for blood pressure regulation on sympathoexcitatory neurons in the rostral ventrolateral medulla of the rat.

We examined whether reticulospinal sympathoexcitatory neurons in the rostral ventrolateral medulla (RVLM) have muscarinic receptors and ACh inputs, and whether these cholinergic mechanisms on RVLM neurons are involved in the pressor response induced by peripheral administration of physostigmine. Microiontophoretic application of ACh and carbachol enhanced the firing rate of RVLM sympathoexcitatory neurons and the enhancement of RVLM neurons by these cholinoceptor agonists was abolished by the nonselective muscarinic receptor antagonist scopolamine and/or by the M2 muscarinic receptor antagonist methoctramine. Physostigmine and the ACh releaser 3,4-diaminopyridine also enhanced the firing rate of RVLM neurons. Intravenous administration of physostigmine enhanced RVLM sympathoexcitatory neuronal activity and the physostigmine-induced response was reversed by iontophoretic application of scopolamine onto the neurons. These results are consistent with the hypothesis that M2 muscarinic receptors responsible for blood pressure regulation are present on RVLM sympathoexcitatory neurons and these receptors receive ACh inputs. Physostigmine injected systemically may exert a portion of its hypertensive effect through a direct enhancement of cholinergic mechanisms on RVLM sympathoexcitatory neurons.

Acetylcholine↗

Expression of highly polysialylated NCAM (NCAM-H) in developing and adult chicken auditory organ.

Neural cell adhesion molecule (NCAM) is highly polysialylated (NCAM-H) in developing tissues, and recent findings suggest that NCAM-H is more essential for neural development than poorly sialylated NCAM (NCAM-L). In order to understand the precise role of NCAM-H in developing and adult inner ears, the immunohistochemical localization of NCAM-H in developing and adult chicken inner ears was examined using a monoclonal antibody which is only specific for NCAM-H. Immunoreactivity of NCAM-H was initially observed on acoustic ganglion at stage 24, when peripheral (afferent) fibers begin to emerge from the ganglion cells. At stage 38, when peripheral fibers form synapses with hair cells, NCAM-H was observed on peripheral fibers and the base of hair cells in the auditory epithelium. At stage 42, NCAM-H on nerve fibers disappeared, and only some acoustic ganglion cells were still positive for NCAM-H. This immunostain on ganglion cells was retained after birth. These data are consistent with the hypothesis that NCAM-H specifically regulates the afferent nerve fibers' growth and synaptogenesis with hair cells during inner ear development and may be associated with processing of auditory information and neuronal plasticity.

Animals↗

Relationship between pulse sequences and signal intensity of joint fluid in the gradient-echo MR imaging.

To depict the labrum and meniscus in terms of contrast to joint fluid by increasing its signal intensity, we examined in vitro and in a human subject the good imaging conditions of gradient-echo magnet resonance by using a 1.0 Tesla superconducting imager (Shimadzu). In our in vitro study, 3 types of joint fluid and physiological saline were imaged together with PVA gel (as the substitute for surrounding soft tissue), by using either the STAGE, SSFP, or STERF method, and with several TR's (repetition time); and mean signal intensity was obtained. In order to confirm the findings of the in vitro study, a human study was conducted: physiological saline was injected into a shoulder joint, and axial planes were depicted under the conditions equivalent to those of the in vitro study. With the STERF method, signal intensity of the fluid was high at any flip angle, but PVS gel and the surrounding soft tissues such as muscles were rarely depicted. With the STAGE and SSFP methods, depiction of the fluid, PVA gel, and the surrounding soft tissues were possible by setting an appropriate flip angle for TR: With the STAGE method (a spoiled gradient echo sequence), good imaging was possible by selecting small flip angle, regardless TR. Therefore, because of easiness in selecting conditions, the STAGE method is considered to be the best for diagnostic scanning.

Humans↗

Initial MRI findings of non-traumatic osteonecrosis of the femoral head in renal allograft recipients.

Fifty-one renal allograft recipients (15-62 years old, mean: 37 years) were monitored for 2.5-6.5 years (average: 4.3 years) after surgery by using magnetic resonance imaging (MRI) to find (i) initial signs of osteonecrosis of the femoral head (ONF), (ii) the presence of bone marrow edema as an initial sign of ONF, (iii) any changes of MRI patterns, and (iv) the relationship between these MRI findings and prognosis. MRI was performed preoperatively (baseline), and whenever possible during the 6-9th week, 12-16th week, 12th month, and yearly thereafter. T1- and T2-weighted images were obtained by using a spin echo technique. Abnormalities were first detected on MRI of 23 femoral heads in 13 patients between 6 weeks and 12 months. All lesions first showed a low intensity band on T1-weighted images and a high intensity band on T2-weighted images. No symptoms or diffuse patterns, such as bone marrow edema, preceded the appearance of the band pattern. After the 12th month, no new abnormal findings on MRI were detected. The lesions were classified into Type A, B, or C, according to the location. 12 of the 16 Type C femoral head lesions, which extend beyond the medial two thirds of the weight-bearing portion of the acetabulum, became symptomatic 7-14 months after transplantation and then progressed to collapse. Bone marrow edema appeared with radiological collapse and symptoms. With the exception of five lesions in three patients who failed to be MR imaged until 12 months postoperatively, all lesions were first detected on MRI within 16 weeks after transplantation. We therefore postulate that the ischemic event that causes ONF will have occurred within 12 weeks after transplantation, considering the time lag of reparative reaction to the dead bone.

Adolescent↗

Analysis of heat shock proteins and cytokines expressed during early stages of osteoarthritis in a mouse model.

OBJECTIVE: Osteoarthritis (OA) is a debilitating disease of the joints. The joints of affected individuals are characterized by a progressive degeneration of articular cartilage leading to inflammation and pain. The expression of heat shock proteins (HSPs) is a ubiquitous self-protective mechanism of all cells under stress, furthermore, the synovium of osteoarthritic individuals contains high levels of cytokines. This study seeks to establish the role of HSPs and cytokines in OA. METHODS: We have investigated the presence of HSPs and cytokines in articular cartilage during early stages of OA in a mouse that is known to develop spontaneous OA lesions (C57 black mouse). The articular cartilage from closely related mice (C57BL/6) was used as control. Messenger RNAs (mRNAs) for HSPs (HSP32, HSP47, HSP60, HSP70, HSP84 and HSP86) and cytokines [interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The mRNA levels of HSP47, HSP70, HSP86, IL-6, and IFN-gamma were up-regulated in the cartilage of C57 black mice, whereas, the level of expression of HSP32, HSP60, HSP84 and IL-1 beta remained unchanged. Furthermore, the expression of IL-1 beta, IL-6, TNF-alpha and IFN-gamma mRNA was associated with expression of HSP60, HSP47, HSP70 and HSP70/HSP86 mRNA, respectively. CONCLUSIONS: The findings in this study suggest that chondrocytes are conditioned under non-physiological stress during early stages of OA, In addition, among HSPs, HSP70 was associated with two different highly expressed cytokines in C57 black mice, indicating the possible role of HSP70 as a characteristic indicator of early stage of OA.

Animals↗

Laryngeal necrosis after combined chemotherapy and radiation therapy.

Post-radiation necrosis of the larynx is a major complication after irradiation and has become rare. Recently, combined chemotherapy and radiation therapy has been introduced for head and neck tumours. The authors report a case of laryngeal necrosis after combination therapy for a patient with cervical lymph node metastases of nasopharyngeal carcinoma and review the literature on late laryngeal necrosis. Although radiation-induced laryngeal necrosis has become a rare complication, the combination of chemotherapy and radiation therapy may increase its incidence. We should always consider it as a possible late complication and treat it appropriately.

Aged↗

Expression of neurite outgrowth factor and gicerin during inner ear development and hair cell regeneration in the chick.

Several cell adhesion molecules are expressed in the developing inner ear. The present study focused on gicerin, a novel member of the immunoglobulin superfamily, in an attempt to improve our understanding of the development and regeneration of chick inner ear. Gicerin is known to homophilically interact with itself and to bind to neurite outgrowth factor (NOF). The data collected herein show that gicerin is highly expressed in auditory epithelium and acoustic ganglion during early embryogenesis. The immunoreactivity of gicerin in the auditory epithelium decreases more rapidly than that in the acoustic ganglion as the mature hair cells become distinguishable. At the post-hatch stage, the expression of gicerin is not observed. In contrast, NOF was expressed on the basement membranes around the auditory epithelium, and in the acoustic ganglion during development and after birth, but not in the auditory epithelium. Following noise damage, gicerin is transiently re-expressed on the damage receptor epithelium when active cell proliferation is observed in the epithelium. This positive reaction immediately disappears as immature short hair cells appear. These results suggest that gicerin may be associated with cell proliferation in the auditory epithelium, and play a role in neurite extension of the acoustic ganglion cells in conjunction with NOF.

Acoustic Stimulation↗

Functional analysis of ssaJ and the ssaK/U operon, 13 genes encoding components of the type III secretion apparatus of Salmonella Pathogenicity Island 2.

We have investigated the structure and transcriptional organization of 13 genes of Salmonella Pathogenicity Island 2 (SPI2) that encode components of the second type III secretion apparatus of Salmonella typhimurium. ssaK, L, M, V, N, O, P, Q, R, S, T, U constitute one operon of 10 kb. ssaJ lles upstream of ssaK and is the terminal gene of another operon. The deduced products of ssaJ, ssaK, ssaV, ssaN, ssaO, ssaQ, ssaR, ssaS, ssaT, and ssaU show greatest similarity to the Yersinia spp. genes yscJ, yscL, lcrD, yscN, yscO, yscQ, yscR, yscS, yscT, and yscU, respectively. The products of the ssaL, ssaM and ssaP genes do not have significant similarity to products of other type III secretion systems, and might be important for the specific function of the SPI2 type III secretion system. Bacterial strains carrying different ssa mutations display minor alterations in terms of serum sensitivity when compared with the wild-type strain, but none are defective in replication within macrophage-like RAW 264.7 cells. However, some of the ssa mutant strains invade HEp2 cells less efficiently and are less cytotoxic to RAW 264.7 macrophages than the wild-type strain. We show that the invasion defect is correlated with a lack of SipC in culture supernatants of these mutant strains. SipC is a product of the SPI1 type III secretion system of S. typhimurium, and is important for epithelial cell invasion. Therefore, mutations in SPI2 can affect the SPI1 secretion system, which raises the possibility of an interaction between the two type III secretion systems.

Amino Acid Sequence↗

Inhibition of gastrulation in Xenopus embryos by an antibody against a cathepsin L-like protease.

An antibody against cathepsin L-like protease (AACLP) was injected into one cell of 2-celled Xenopus embryos. The blastopores of AACLP-injected embryos either did not invaginate or failed to complete invagination. As a result of this failure to complete gastrulation, the body axes could not form normally and tail bud stage embryos were bent dorsally. Embryos injected with a control antibody (CA) developed normally through the tadpole stage. Mesodermal induction was not inhibited in embryos exhibiting this AACLP-induced gastrulation defect, but the mesodermal structure of these embryos was organized incorrectly due to the defective gastrulation during the early stages.

Animals↗

Expression of plasma membrane water channel genes under water stress in Nicotiana excelsior.

Deduced amino acid sequences encoded by the cDNAs related to the MIP gene family from Nicotiana excelsior were characterized. Phylogenetic characterization of the products of corresponding genes named NeMip1, NeMip2, and NeMip3 strongly suggested that they are water channel proteins localized in the plasma membrane. Organ specificity of the gene expression was examined in leaves, roots, and reproductive organs. NeMip1 was expressed in roots and reproductive organs; however, it was hardly detectable in leaves. Two other genes, NeMip2 and NeMip3, were expressed in all of organs examined. mRNA accumulation from the genes was investigated in leaves under salt- and drought-stresses. The results demonstrated that mRNA accumulation from all three genes increased under salt- and drought-stresses within one day. However, they showed different accumulation patterns. In addition to their up-regulation under salt- and drought-stresses, daily changes in NeMip2 and NeMip3 mRNA accumulation was observed under unstressed conditions in leaves.

Amino Acid Sequence↗

Effect of heat on cambial reactivation during winter dormancy in evergreen and deciduous conifers.

Responses of cambium to warming were recorded three times (December 14-27, 1990, January 18-February 3 and February 27-March 13, 1991) on 14-year-old Cryptomeria japonica D. Don and four times (December 12-26, 1990, January 18-February 2, February 26-March 12 and March 28-April 13, 1991) on 27-year-old Larix leptolepis Gord., during a period of winter cambial dormancy. Stem surfaces at breast height, mid-tree height and the crown base were warmed to 25-30 degrees C for 2 weeks. After heat treatment, cambia in the treated regions and in untreated regions 1 m above each treated area were examined by optical and transmission electron microscopy (TEM). In C. japonica, heat treatment often resulted in cambial reactivation in the treated regions, and this response to heat gradually increased as the dormant season passed from winter to spring. Conversely, in L. leptolepis, no cell division was observed in the cambial region of warmed stems until natural resumption of cambial activity, which occurred after bud break.

Journal Article↗

Triazine dyes inhibit HIV-1 entry by binding to envelope glycoproteins.

We have attempted to purify envelope (Env) glycoproteins of human immunodeficiency virus (HIV) from the culture supernatants of CHO-Sec cells that secreted truncated 140-kDa precursor and mature 120-kDa Env glycoproteins. The concentrated culture supernatants were applied to a column coupled with cibacron blue 3GA (CB3GA) to separate albumin from the Env proteins because CB3GA, a triazine dye, has been known to have a high affinity to albumin. Unexpectedly, Env proteins as well as albumin bound to the column, and the bound Env proteins were eluted by increasing the ionic strength using KCl. Gp120 was eluted at 0.5-0.9 M of KCl, while a higher concentration (0.9-1.5 M) was necessary for the elution of gp140. The agarose gel coupled with reactive red 120 (RR120), another triazine dye with similar characteristics, also retained both Env proteins, and the bound Env proteins could be eluted in a similar manner. In addition, these agents inhibited syncytium formation caused by HTLV-IIIB and HTLV-IIIMN. Inhibition was also seen when a virus-free fusion assay between Env protein expressed in CHO cells and fluorescent labeled SupT1 cells were used. These findings indicate that triazine dyes bind to the functional regions of Env proteins of HIV-1 that play important role(s) for HIV infection.

Albumins↗

Effect of maternal exercise on fetal umbilical artery waveforms: the comparison of IUGR and AFD fetuses.

OBJECTIVE: To determine the effect of maternal exercise on the fetal blood flow of normal and growth-retarded fetuses. METHODS: The effect of maternal exercise on fetal blood flow was investigated with 24 pregnant women between 36 and 42 weeks' gestation. Seventeen pregnancies were uncomplicated (normal group) and the other 7 were complicated with growth-retarded fetuses (IUGR group). They underwent graded walking on a treadmill with an upper limit of 150 bpm for the maternal heart rate. The systolic over diastolic velocity ratio (S/D ratio) of the umbilical artery was measured before exercise, and at 3, 5, 10, and 15 minutes after exercise. RESULTS: The mean S/D ratio of the IUGR group before exercise was significantly higher than that of the normal group (p < 0.05). The S/D ratio did not change significantly after exercise, in either the normal group or the IUGR group. CONCLUSION: This study suggests that maternal exercise at this level of intensity and duration does not have any harmful effect, even on growth-retarded fetuses that might have placental dysfunctions.

Diastole↗

Effect of growth hormone on fatty liver in panhypopituitarism.

A 17 year old boy was admitted because of short stature and hepatomegaly. He was diagnosed with panhypopituitarism and fatty liver. The fatty liver improved, not with hydrocortisone or levothyroxine treatment, but with growth hormone administration. The fatty liver in this patient was attributable to a growth hormone deficient state.

Adolescent↗

Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia.

A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, a C to T substitution at nucleotide 677, is responsible for reduced MTHFR activity and associated with modestly increased plasma homocysteine concentrations. Since underlying maternal vascular disease increases the risk of pre-eclampsia, we had the working hypothesis that pre-eclampsia patients would have an increased T677 allele frequency compared with controls. The MTHFR genotypes were determined in 67 pre-eclampsia patients, 98 normal pregnant women, and 260 healthy adults by the PCR/RFLP method. The T677 allele and the genotype homozygous for the T677 allele were significantly increased in the pre-eclamptic group compared with the controls (p < 0.02 and p < 0.004, respectively). The data indicate that the T677 variant of the MTHFR gene is one of the genetic risk factors for pre-eclampsia.

Adult↗

Pregnancy increases ET-1-induced contraction and changes receptor subtypes in uterine smooth muscle in humans.

The purpose of the present study was to investigate whether pregnancy affects endothelin (ET)-1-induced contraction, the density ofET receptors, and the ratio of receptor subtypes (ET(A) and ET(B)) in uterine smooth muscle in humans. We also investigated which ET receptor subtypes mediate ET-1-induced contraction in the human uterus. In uterine membrane preparations, (125)I-labeled ET-1 ((125)I-ET-1) binding sites (Bmax) in pregnant women did not differ from those in age-matched nonpregnant women (596.2 +/- 107.1 vs. 512.1 +/- 167.7 fmol/mg protein). The dissociation constant (Kd) in pregnant women did not differ from that in nonpregnant women. Competitive displacement experiments with (125)I-ET-1 binding to the membranes using BQ-123 (ET(A) receptor antagonist) showed that the percentage of ET(A) receptors in uterine muscle was significantly higher in pregnant women than in nonpregnant women (P < 0.01). The calculated ratios of ET(A) to ET(B) receptors in pregnant and nonpregnant uteri were 92:8 and 68:32, respectively. Combination treatment with BQ-788 (ET(B) receptor antagonist) completely inhibited the BQ-123-resistant component of (125)I-ET-1 specific binding. ET-1 caused dose-dependent contractions in isolated human uteri from both pregnant and nonpregnant women. The maximum response was markedly greater in pregnant women than in nonpregnant women, whereas pD2 (-log[EC50]) values did not differ between pregnant and nonpregnant uteri. In pregnant human uterus, BQ-123 (10(-6) M) significantly shifted the dose-dependent curve of ET-1 response to the right, whereas BQ-3020 (ET(B) receptor agonist) did not cause contraction. These results suggested that ET-1-induced contraction of the human uterus is mediated through only ET(A) receptors and that ET-1-induced uterine contraction in humans is markedly increased during pregnancy. In addition, the present study suggests that, although (125)I-ET-1 Bmax are not altered during pregnancy, the proportion of ET(A) receptors is increased and that of ET(B) receptors is decreased in the pregnant human uterus.

Adult↗