Biomedical subjects

Y Uematsu

Publications and source records attributed to Y Uematsu.

At least 37 records · Page 2Linked to original sources

PubMed2000

[Cell transplantation therapy for Parkinson's disease].

We found that Parkinson's disease(PD) patients receiving autotransplants of the cervical sympathetic ganglia show a significant improvement in the parkinsonian symptoms with a consequent reduction in the daily intake of levodopa. The grafting procedure have recently been modified to further enhance the efficacy of the transplantation. Thus, in order to increase the amount of donor tissue we opted for the endoscopically excised thoracic sympathetic ganglia as a donor. With the aid of CT-guided stereotaxic surgery, we unilaterally placed one transplant deposit in the caudate head and three deposits in the putamen. Four patients that had received the grafts were followed with antiparkinsonian medication being unchanged at least one year postgrafting. Although no patients exhibited a substantial improvement in motor performance rated in either "on" or "off" phase, the awake time spent in "off" phase was reduced by 30-40% in all the patients. In two patients, dyskinesia in "on" phase was also attenuated. Our new transplantation paradigm is encouraging and deserves further investigation.

Cell Transplantation↗

PubMed1999

A mutant of deleted variant of hepatocyte growth factor (dHGF) with alanine substitution in the N-terminal basic region has higher activity in vivo.

In a previous study, we generated a mutant of dHGF (deleted variant of hepatocyte growth factor), termed #2, with higher specific activity than dHGF in assays of mitogenic activity on rat hepatocytes and America opossum kidney epithelial cells (OK). In the present study, we examine in vivo hepatotropic and renotropic activities of #2 and its distribution to target tissues, liver and kidney. Administration of #2 to normal rats significantly increased serum levels of total protein, albumin, free-cholesterol, and HDL-cholesterol and liver weight in a dose-dependent manner. Analysis of these parameters suggests that #2 is more potent than dHGF as a hepatotropic factor in vivo. In addition, #2 reduced mortality of mercuric chloride-administered mice and the effect was stronger than that of dHGF. When injected to mice, a larger amount of #2 than dHGF was rapidly distributed to the liver. Sixty minutes after injection, the concentrations of #2 in plasma, liver, and kidney were higher than those of dHGF. These distribution properties and the higher mitogenic activity in vitro may explain why #2 exerts more potent in vivo biological activity than dHGF.

Acute Kidney Injury↗

PubMed1999

Effective administration route for the deleted form of hepatocyte growth factor To exert its pharmacological effects.

The pharmacokinetics and the pharmacological effects of the deleted form of hepatocyte growth factor (dHGF) after intravenous (iv), subcutaneous (sc), or intramuscular (im) administration (0.25 and 2. 5 mg/kg) were studied in rats. After single iv administration (2.5 mg/kg), dHGF in serum rapidly decreased (alpha- and beta-phase half-life: 3.2 and 26.5 min, respectively). Two to four hours after single sc or im administration (2.5 mg/kg), the serum level of dHGF reached a maximum and then gradually declined (half-life: 2.7 h). The serum levels were not changed by repetitive iv administration, but were dramatically decreased by repetitive sc or im administration. Liver weight and serum levels of total protein, albumin, and HDL-cholesterol were significantly increased by iv administration of dHGF (twice daily for 4 days at 0.25 mg/kg). Sc or im administration of dHGF did not increase these parameters at the same dose, but did significantly at 2.5 mg/kg. These observations suggest that iv administration is the most effective in exerting the pharmacological effects of dHGF among three administration routes. dHGF after iv administration was distributed mainly and rapidly into liver (53.6% of the injected dHGF within 5 min) and was sustained at a higher level in the liver than in plasma. In infusion (0.5 mg/kg/3 h), dHGF level in plasma and liver reached a steady-state 15 and 60 min after starting the infusion, respectively. The steady-state level of dHGF was 7- to 9-fold higher in liver than in plasma, and the higher level in liver was sustained beyond the steady-state.

Animals↗

PubMed1999

[Choroid plexus papilloma in the posterior third ventricle in infancy: a case report].

Choroid plexus papillomas represent approximately 0.5% of all intracranial tumors, but they are found in the third ventricle only infrequently. We report a case of choroid plexus papilloma in the third ventricle which is difficult to differentiate from a pineal region tumor. A 4-month-old female presented with bulging fontanelle and sunset phenomenon. A CT scan and MRI showed marked hydrocephalus caused by a tumor extending from the posterior third ventricle to the peneal body. Preoperatively, we diagnosed the lesion as a pineoblastoma. The tumor was totally removed through the occipital transtentorial approach. Pathological examination of the tumor revealed a typical choroid plexus papilloma. The operation was uneventful, and she has grown normally without recurrence of the tumor for three years since the operation. A sagittal gadolinium-enhanced MRI was useful in our case to differentiate a choroid plexus papilloma from a pineal region tumor, because the former extended into the aqueduct forming the shape of the letter V while the latter compressed the aqueduct downward.

Cerebral Ventricle Neoplasms↗

PubMed1998

Binding of hepatitis C virus to CD81.

Chronic hepatitis C virus (HCV) infection occurs in about 3 percent of the world's population and is a major cause of liver disease. HCV infection is also associated with cryoglobulinemia, a B lymphocyte proliferative disorder. Virus tropism is controversial, and the mechanisms of cell entry remain unknown. The HCV envelope protein E2 binds human CD81, a tetraspanin expressed on various cell types including hepatocytes and B lymphocytes. Binding of E2 was mapped to the major extracellular loop of CD81. Recombinant molecules containing this loop bound HCV and antibodies that neutralize HCV infection in vivo inhibited virus binding to CD81 in vitro.

Amino Acid Sequence↗

PubMed1998

Radiculopathy after laminoplasty of the cervical spine.

STUDY DESIGN: The risk factors of patients with and without radiculopathy after laminoplasty of the cervical spine were compared retrospectively. OBJECTIVES: To study the association between risk variables and postlaminoplastic radiculopathy to clarify the pathogenesis of radiculopathy and to devise preventive measures. SUMMARY OF BACKGROUND DATA: Radiculopathy after cervical laminoplasty on the expanded side has been attributed mainly to traumatic surgical techniques, whereas radiculopathy on the hinged side has been attributed to traction, tethering, or kinking of the nerve root that has resulted from posterior shift of the spinal cord from the preoperative position. There is still much divergence of opinion concerning the risk factors for the outbreak as well as the prevention. METHODS: Of 365 patients who had undergone laminoplasty, 20 patients (5.5%) developed postoperative radiculopathy. Using data from postoperative computed tomography scans and other sources, these patients were compared with 211 patients with no radiculopathy, who had undergone laminoplasty during the same period, to identify risk factors related to patient characteristics and surgical techniques. RESULTS: Of various risk factors studied, the narrowest level of the spinal canal, preoperative symptomatic severity, flatness of the spinal cord assessed by computed tomography myelography at C4-C5, cervical curvature, anterior protrusion of the superior articular process as assessed by computed tomography scan, laterality of the osteophytes, and ossification of the posterior longitudinal ligament could not significantly discriminate between patients with and without postoperative radiculopathy. The angle of lamina as measured by using computed tomography scans obtained after expansion in the patients with radiculopathy was greater than 68 degrees on the opened and hinged sides and was significantly greater than the angle in patients without radiculopathy (P < 0.05). The incidence of radiculopathy on both the opened and hinged sides was significantly higher in patients in whom the bony gutter had been cut on the lateral side of the medial aspect of the zygapophyseal joint. CONCLUSION: Any one of patients' characteristics could not be correlated with postoperative cervical radiculopathy in this study. To prevent postoperative radiculopathy, it may be important during surgery to place the bony gutter on the medial side of the zygapophyseal joint and to keep the slope of the opened lamina within 60 degrees.

Adult↗

PubMed1998

[Long-term follow up of QRS axis deviation].

It has been already described that the average axis of QRS complex is deviated by aging as well as various diseases, such as ventricular overload or bundle branch block. In this study, we first tested the hypothesis that the extra-cardiac factor changes with aging, such as the body shape or diaphragm position, which are represented by body weight (WT) and/or cardiac-thoracic ratio (CTR), are the main cause of QRS axis deviation. In 28 cases including 1 right (RAD) and 27 left axis deviation (LAD) patients whose QRS axis have been deviated during observed periods, WT and X-ray CTR were compared to the degree of axis deviation. Unfortunately no clear relationship was found among these parameters. On the other hand, in 8 cases out of 27 LAD patients, confirmed or suspected left anterior hemiblock (LAH) was found by vector electrocardiogram. Pathological studies showed that the degeneration of the stimulation pathway occurred with aging and it caused the bundle branch block. Therefore, we conclude that the degenerative change in left anterior stimulation pathway by aging should be, at least, one of the cause of the QRS axis deviation.

Aged↗

PubMed1997

Long-lasting salivation induced by a novel muscarinic receptor agonist SNI-2011 in rats and dogs.

The sialogogic effect of SNI-2011, a novel muscarinic receptor agonist, (+/-)-cis-2-methylspilo [1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate, was compared with that of pilocarpine hydrochloride in a dose range in which the two muscarinic agonists exhibited approximately similar efficacy in eliciting salivation. Pilocarpine (0.66-2.0 mg/kg, i.d.) induced a marked but short-lasting salivation in rats, whereas the salivation induced by SNI-2011 (20-60 mg/kg, i.d.) lasted 1.4- to 1.8-fold longer. In dogs, the sialogogic effect of SNI-2011(1-3 mg/kg, i.v.) also lasted about 2-fold longer than that of pilocarpine (0.1-0.3 mg/kg, i.v.). The plasma SNI-2011 level that caused salivation at a rate of 0.4 ml/min was about 100 ng/ml and higher rates of salivation (over 0.4 ml/min) induced by 1 mg/kg SNI-2011 lasted for about 90 min in dogs. The plasma pilocarpine level that caused salivation at a rate of 0.4 ml/min was about 25 ng/ml and the higher rate of salivation (over 0.4 ml/min) induced by 0.1 mg/kg pilocarpine lasted only for 20 min in dogs. Effective plasma levels of SNI-2011 persisted longer than those of pilocarpine. These results indicate that SNI-2011 may be useful in the treatment of xerostomia because of its long-lasting sialogogic action.

Animals↗

PubMed1997

Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning.

1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily. However, the molecular basis for the actions of 1 alpha,25(OH)2D3 in bone formation, its role during development and VDR genetic polymorphisms for predicting bone mineral density are uncertain. To investigate the functional role of VDR, we generated mice deficient in VDR by gene targeting. We report here that in VDR null mutant mice, no defects in development and growth were observed before weaning, irrespective of reduced expression of vitamin D target genes. After weaning, however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia and infertility, and bone formation was severely impaired as a typical feature of vitamin D-dependent rickets type II (refs 8, 9). Unlike humans with this disease, most of the null mutant mice died within 15 weeks after birth, and uterine hypoplasia with impaired folliculogenesis was found in female reproductive organs. These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D-deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage.

Alopecia↗

PubMed1997

Impairment of short-term memory in left hemispheric traumatic brain injuries.

We report on two patients with traumatic lesions in the temporal and parietal lobes who demonstrated disturbances of short-term memory (STM) following improvement on the aphasia. Patient 1 was a 66-year-old right-handed man who presented to our hospital with a cerebral contusion. One admission we observed a Wernicke's aphasia with paraphasic jargon in this patient that resolved within 8 weeks. Patient 2 was a 35-year-old right-handed woman, with an acute subdural haematoma and a cerebral contusion, who underwent craniotomy and evacuation of the haematoma. In this patient we noted a transient Wernicke's aphasia following the operation that improved within 3 months. Linguistically, the aphasia observed in each of these two patients was not a typical conduction aphasia because of the absence of paraphasia, and impairment of comprehension was unclear despite a decrease in performance on repetition tasks. Both verbal and non-verbal tasks suggested an impairment in STM. These findings suggest that involvement of the left hemisphere may cause disturbances in both verbal and non-verbal STM.

Adult↗

PubMed1997

Thymocytes control the CD4 gene differently from mature T lymphocytes.

We analyzed the activity of the enhancer, the promoter and the silencer of the human CD4 gene during T cell development using transgenic mice. Immunofluorescence studies on thymic populations of mice carrying transgenes in various combinations of these regulatory DNA elements revealed that thymocytes control the CD4 gene in a different manner than mature peripheral T lymphocytes. The 5'-positive regulatory unit, consisting of the promoter and the 5' enhancer, is already active at the CD4-CD8-double-negative (DN) stage of development. However, its activity becomes lower in the double-positive and a fraction of the CD4+ CD8int/- cell population, indicating that an additional enhancer, located in either the first or the third intron of the CD4 gene, is required for CD4 gene expression in this population. The other studied regulatory element is the minimal CD4 silencer which inhibits CD4 gene expression in peripheral CD8 T lymphocytes. This silencer is inactive in the most immature DN thymocytes, which probably use a distinct silencer mechanism to down-regulate CD4 gene expression. Unexpectedly, the CD4 silencer is also active in CD4+ CD8int/- cells of the thymus, implying that an anti-silencer may be required to resume CD4 expression in this cell population. Altogether, the CD4 gene is regulated by several positive and negative regulatory mechanisms which come into play in a developmentally coordinated manner.

Animals↗

PubMed1997

Transplantation of autologous sympathetic ganglion into the brain with Parkinson's disease. Long-term follow-up of 35 cases.

Transplantation of autologous sympathetic ganglion was performed in 35 patients with Parkinson's disease. Approximately half the patients showed improvement of parkinsonian symptoms over the 3 years following transplantation. The patients showed amelioration of bradykinesia and gait disturbance, but tremor and muscle rigidity were not improved by transplantation. The other half of the patients did not show amelioration after transplantation. No serious complications were encountered, though mild ptosis was observed in all patients. The mechanism of improvement of symptoms might be the release of dopamine from the grafted sympathetic ganglion. Transplantation of autologous sympathetic ganglion can be a therapeutic modality for Parkinson's disease.

Adult↗

PubMed1997

[QRS axis shift in deep breathing].

We examined changes in mean QRS axis of electrocardiogram during the deep breathing test in outpatients with hypertension, ischemic heart disease, and/or diabetes mellitus. The mean age of all patients (n = 596; male 327, female 269) was 63.0 years (male 62.7 years, female 63.4 years). The average of the mean QRS axis in all patients was shifted to the right during deep inspiration. The changes in mean QRS axis during deep breathing test were more than 60 degrees in 27 patients (4%) (mean age: 70.0 years), 30-59 degrees in 118 patients (20%) (mean age: 65.5 years), and 0-29 degrees in 451 patients (76%) (mean age: 61.9 years). These results suggest that the changes in mean QRS axis during deep breathing are greater in the aged patients.

Aged↗

PubMed1996

Identification and characterization of a human CD4 silencer.

Using transgenic mice, we have identified a human CD4 silencer contained within a 484-bp fragment in the first intron of the CD4 gene. Further experiments have mapped a lineage-specific silencing activity to a region of 190 bp. This region contains two protein-binding sites detected by deoxyribonuclease I footprinting analyses. Tested in transient transfection assays, these two DNA elements showed significant silencing activity restricted to the CD8 phenotype. In CD4 cells, either no clear effect (FP I) or strong enhancing activity (FP II) was observed by transient transfection assays. Despite the lineage-specific activity of these two elements, electrophoretic mobility shift assays (EMSA) showed similar levels of protein binding to the silencer element FP I in CD4 and CD8 T cells. Base substitutions in the FP I fragment abolished the silencing activity in transfected CD8 cells as well as the protein binding in EMSA, suggesting an important role of this protein-DNA interaction in CD4 gene regulation.

Animals↗

PubMed1996

Transcortical mixed aphasia with left frontoparietal lesions.

We present a case of transcortical mixed aphasia following a left frontoparietal infarct caused by vasospasm after subarachnoid haemorrhage. Although CT showed low-density areas in the left frontal lobe and basal ganglia, single photon emission CT revealed a wider area of low perfusion over the entire left hemisphere, except for the left perisylvian speech areas. Hence, transcortical mixed aphasia may be caused by the isolation of perisylvian speech areas due to disconnection from surrounding areas.

Aphasia↗

PubMed1996

Intron retention generates a novel isoform of the murine vitamin D receptor that acts in a dominant negative way on the vitamin D signaling pathway.

We identified and characterized a novel rat vitamin D receptor isoform (rVDR1), which retains intron 8 of the canonical VDR (rVDR0) during alternative splicing. In this isoform protein directed by the stop codon in this newly identified exon, a part of the ligand binding domain (86 amino acids) is truncated at the C-terminal end but contains 19 extra amino acids. The rVDR1 transcript was expressed at a level 1/15 to 1/20 of that of rVDR0 in the kidney and intestine in adult rats but not in embryos. The recombinant rVDR1 protein showed no ligand binding activity. Homo- and heterodimers of the recombinant rVDR0 and rVDR1 proteins bound to a consensus vitamin D response element (VDRE) but not to consensus response elements for thyroid hormone and retinoic acid. However, unlike rVDR0, rVDR1 did not form a heterodimeric complex with RXR on the VDRE. A transient expression assay showed that this isoform acted as a dominant negative receptor against rVDR0 transactivation. Interestingly, the dominant negative activities of rVDR1 differed among VDREs. Thus, the present study indicates that this new VDR isoform negatively modulates the vitamin D signaling pathway, through a particular set of target genes.

Alternative Splicing↗

PubMed1995

T cell receptor gamma delta repertoire is skewed in cerebrospinal fluid of multiple sclerosis patients: molecular and functional analyses of antigen-reactive gamma delta clones.

To study the relevance of gamma delta T cells in multiple sclerosis (MS) we analyzed the T cell receptor (TCR) gamma delta repertoire and the antigen reactivity of gamma delta clones isolated from cerebrospinal fluid (CSF). In T cell cultures derived from CSF we found an increased percentage of V delta 1+ cells as compared to peripheral blood of the same donors. Phenotypic analysis of cells from MS CSF with V gamma- and V delta-specific monoclonal antibodies (mAb) showed that the V delta 1 chain is most frequently associated with gamma chains belonging to the V gamma 1 family. Sequence analysis of TCR genes revealed heterogeneity of junctional regions in both delta and gamma genes indicating polyclonal expansion. gamma delta clones were established and some recognized glioblastoma, astrocytoma or monocytic cell lines. Stimulation with these targets induced serine esterase release and lymphokine expression characteristic of the TH0-like phenotype. Remarkably, these tumor-reactive gamma delta cells were not detected in the peripheral blood using PCR oligotyping, but were found in other CSF lines independently established from the same MS patient. Altogether, these results demonstrate that in the CSF there is a skewed TCR gamma delta repertoire and suggest that gamma delta cells reacting against brain-derived antigens might have been locally expanded.

Adolescent↗

PubMed1995

Transplantation of cultured sympathetic ganglionic neurons into parkinsonian rat brain: survival and function of graft.

The superior cervical ganglia (SCG) of newborn rats, which had been cultured as explants for varying periods of time, were transplanted into the striatum of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway to examine the survival and functional properties of the sympathetic neurons maintained in long-term culture prior to grafting. In the rats given the SCG cultured in vitro for 2 weeks, apomorphine-induced rotational behaviour was satisfactory reduced. The rats receiving the SCG from 4-week-old cultures showed only modest behavioural changes. The grafting of the SCG cultured for 6 weeks in vitro did not affect the rotational behaviour. These behavioural data corresponded with the histological assessment of the graft survival by use of catecholamine histofluorescence. The present results suggest the critical time period in vitro which might allow the cultured sympathetic neurons to be successfully grafted.

Animals↗