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T Kondoh

Publications and source records attributed to T Kondoh.

At least 145 records · Page 8Linked to original sources

Development of human fetal ventral mesencephalic grafts in rats with 6-OHDA lesions of the nigrostriatal pathway.

Neuronal transplantation is an approach that can be exploited to study the development of the human central nervous system as well as being used in attempts to restore neurological function. In the present study, we have examined cellular events that appear to precede the development of dopamine nerve fiber extension by neurons from the human fetal ventral mesencephalon. These cellular events were examined using neuronal cell suspensions from human fetal ventral mesencephalic tissue (gestational ages 7-10 weeks) transplanted into the striatum of unilaterally lesioned 6-hydroxydopamine (6-OHDA) rats. Animals were sacrificed for immunohistochemistry 9-10 weeks after the transplantation prior to the manifestation of behavioral recovery. Histological analysis revealed tyrosine hydroxylase (TH) immunoreactive neurons in the grafts. The majority of these neurons had very short TH positive processes (60-70 microns), indicating that the maturation of grafted dopaminergic neurons was still incomplete. Immunostaining for the human specific intermediate neurofilament (hNF, clone: BF-10) showed dense neuronal fibers in the grafts. These fibers extended deeper into the host brain than the TH positive neuronal processes. The whole striatum, particularly the medial part of the striatum, exhibited long NF positive processes. Glial fibrillary acidic protein (GFAP) immunohistochemistry revealed fine astrocytic processes inside the grafts, which were clearly different from host reactive glial cells surrounding the grafts. These graft-derived glial processes tended to extend into the host brain deeper than the TH positive neuronal processes from the grafts. These early histological findings of the grafted human fetal ventral mesencephalon suggest that the graft-derived NF positive neuronal processes, as well as the glial processes, radiate from the grafted tissue and extend into the host brain prior to the extension of TH positive processes. These results further suggest that human-to-rat xenografts can be used to study the neural development of human fetal brain tissue.

Animals↗

A comparison of three methods used for treatment of ranula.

PURPOSE: This report compares the treatment results for oral and plunging ranulas. PATIENTS AND METHODS: Twenty-seven patients were retrospectively examined concerning treatment methods and recurrence on the basis of their medical records. The surgical specimens were also examined microscopically. RESULTS: Four patients had excision of the ranula only, 22 had marsupialization, and nine had removal of the sublingual gland combined with the excision of the ranula. These treatments showed a 25.0%, 36.4% and 0% recurrence rate, respectively. Histological observation revealed no epithelial lining in any of the examined specimens. CONCLUSIONS: Removal of the sublingual gland combined with the ranula was the most reliable method among the above three used.

Humans↗

Collagenase-induced intrastriatal hemorrhage in rats results in long-term locomotor deficits.

UNLABELLED: BACKGROUND AND PURPOSE. Previous studies have shown that injection of the metalloproteinase collagenase directly into the caudate nucleus of rats causes an intracerebral hemorrhage. The purpose of the present study is to determine functional deficits associated with a collagenase-induced hemorrhagic lesion of the striatum. METHODS: Twelve adult rats received a 2-microL infusion of bacterial collagenase (0.5 U in saline) into the right striatum. The rotational response to apomorphine (1 mg/kg SC) administration was then examined at 1, 4, 7, 21, 35, and 70 days after the surgery. In addition to the rotational asymmetry studies, the initiation of stepping movements in each forelimb was determined 8 weeks after the collagenase injections. In the assessment of rotational asymmetry and stepping ability, an additional six control animals received unilateral injections of saline alone. After behavioral testing, brains were processed for neuropathological evaluation. RESULTS: A net ipsilateral rotation was noted at all posthemorrhage time periods. The average rotational asymmetries on these days were 14.57 +/- 2.9, 20.33 +/- 2.7, 19.99 +/- 4.4, 18.95 +/- 4.9, 17.03 +/- 4.9, and 14.4 +/- 4.7, respectively (data expressed as mean clockwise rotations per 5 minutes +/- SEM). The average number of steps initiated by the forelimb ipsilateral and contralateral to the lesion was 28.3 +/- 2.1 steps per minute and 13.6 +/- 1.5 steps per minute, respectively. This difference between left and right forelimb stepping was stable and reproducible for 3 consecutive days. Histological studies revealed a long-lasting hematoma cavity surrounded by dense reactive gliosis in the striatum. CONCLUSIONS: We conclude that collagenase-induced intrastriatal hemorrhage results in long-term locomotor deficits and is therefore a useful model for developing and assessing therapeutic approaches for the restoration of neurological function after intracerebral hemorrhage.

Animals↗

Alterations in striatal dopamine release and reuptake under conditions of mild, moderate, and severe cerebral ischemia.

Cerebral ischemia can result in varying degrees of tissue damage. Conditions of severe ischemia can produce extensive areas of irreversible injury, whereas in conditions of moderate ischemia, tissue damage may be reversible, as in the region of the ischemic penumbra. The reversibility of tissue damage in the penumbral region is of clinical interest, because the characterization of conditions underlying this reversible state may provide information needed for the development of new therapeutic approaches for treatment. Our previous studies demonstrated neurochemical alterations in the levels of dopamine (DA) within the striatum after cerebral ischemia. In the present study, we postulate that these changes may be caused, in part, by alterations in transmitter release and reuptake. To test this hypothesis, forebrain ischemia was induced in Sprague-Dawley rats (Harlan, Indianapolis, IN) by means of bilateral common carotid artery occlusion and hemorrhagic hypotension. Cerebral blood flow (CBF) in the striatum was measured by the method of hydrogen clearance, and the extracellular DA ([DA]e) levels were measured by in vivo microdialysis. Varied reductions of CBF were induced and maintained for 5 hours. Three subgroups were established retrospectively according to the degree of CBF reduction: 67.7, 35.6, and 13.2% of normal CBF in the mild, moderate, and severe ischemic groups, respectively. The induction of ischemia resulted in 1.9-, 9.3-, and 122.3-fold increases in [DA]e above baseline in the mild, moderate, and severe ischemia groups, respectively. At 3 hours after the induction of ischemia, high potassium (100 mmol/L) or Nomifensin (Sigma, St. Louis, MO) (10 mmol/L), a DA uptake blocker, was administrated via a microdialysis probe to stimulate DA release while reductions in CBF were maintained continuously. Thirteen rats were used in the study of the release of DA by potassium or Nomifensin in nonischemic conditions. The administration of high potassium or Nomifensin stimulated DA release in conditions of mild and moderate ischemia. The increase in DA release by potassium stimulation was higher in rats with mild ischemia (106.6-fold) than that in normal rats (22.3-fold). This suggests a hyperexcitability of DA terminals under mild ischemia, as compared with nonischemic conditions. On the other hand, Nomifensin increased [DA]e levels more in moderately ischemic brains than in control brains, suggesting that DA uptake is up-regulated in the former case. The increased release of DA by potassium and Nomifensin was sustained after stimulation in conditions of mild and moderate ischemia. The high level of [DA]e with severe ischemia after ischemic induction was sustained throughout the period of study and was not stimulated by potassium or Nomifensin. We conclude that under conditions of mild and moderate ischemia, DA terminals become highly excitable and reuptake mechanisms are compromised. These changes of DA metabolism during mild and moderate ischemia may explain the sustainability of neurons in the "penumbra" condition of cerebral ischemia and the transformation of the ischemic penumbra to a necrotic core.

Animals↗

Factors influencing nifedipine-induced gingival overgrowth in rats.

Factors such as age, the dose of nifedipine administered in the diet, serum drug level, duration of drug administration, and sex which may influence nifedipine-induced gingival overgrowth were examined in a rat model using 20-, 50-, and 90-days-old male and female rats. Oral administration of nifedipine (50 to 250 mg/kg diet) increased the serum level of the drug in a dose-dependent manner in both males and females. However, a higher serum level was required in females than males to attain the same degree of gingival overgrowth. The minimum dietary concentrations of the drug required to elicit gingival overgrowth in males and females were 150 and 100 mg/kg, respectively, which gave respective minimum serum levels of 800 and 1100 ng/ml. The degree of overgrowth depended on the serum concentration of the drug after it had reached the required minimum in male and female animals. Administration of nifedipine (250 mg/kg diet) for 20 days was enough to induce maximal overgrowth, but this induction occurred only in rats that started to receive the drug when they were 20 days old, not in those that started at 50 and 90 days of age for the same administration period of 55 days, and the overgrowth regressed and the gingiva were normal 40 days after ceasing drug administration. These results suggest that gingival overgrowth occurred in accordance with the drug concentration in the diet, as well as that in the serum, and was more likely to occur in males and younger individuals.

Age Factors↗

Detection of coronary artery disease using 12-lead electrocardiogram and simultaneous dual myocardial imaging with iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) and thallium-201 in patients with unstable angina.

We investigated the usefulness of 12-lead electrocardiogram and simultaneous single-photon emission computed tomography (SPECT) with 123I-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) and thallium-201 (201Tl) for detecting coronary artery disease (CAD) in 54 consecutive patients with unstable angina. Discordant BMIPP uptake was defined as less 123I-BMIPP uptake than 201Tl uptake in 123I-BMIPP/201Tl dual SPECT. In the detection of CAD, ischemic electrocardiographic change during anginal attack had high sensitivity and low specificity, while discordant BMIPP finding had low sensitivity and high specificity. In patients showing ST depression during anginal attack, discordant BMIPP uptake showed high sensitivity and high specificity for detecting CAD. In conclusion, both 12-lead electrocardiogram during anginal attack and discordant BMIPP uptake are useful in detecting CAD in patients with unstable angina.

Adult↗

Neurohumoral factor responses to mental (arithmetic) stress and dynamic exercise in normal subjects.

We examined the responses of plasma catecholamine and plasma renin activity (PRA) during mental (arithmetic) stress and dynamic exercise in 15 normal subjects. Compared to rest values, there was a significant increase in the plasma epinephrine concentration (E), but not in the plasma norepinephrine concentration (NE) or PRA during mental arithmetic. During dynamic exercise, there were significant increases in both NE and E and in PRA. The ratio of E to NE was significantly higher during mental arithmetic than during dynamic exercise. NE was significantly correlated with PRA at rest, during mental arithmetic and dynamic exercise. No significant correlations were observed between E and PRA. Dynamic exercise primarily induces a sympathetic nervous response, and mental (arithmetic) stress mainly induces an adrenal response. The renin-angiotensin-aldosterone system response may in part be regulated by sympathetic nervous activity during both mental (arithmetic) stress and dynamic exercise.

Adult↗

[The assessment of quick turnaround service in clinical laboratories].

The quick turnaround service of laboratory data has been a basic and fundamental service of clinical laboratories. To realize this service, there are three basic requirements in the hospital and laboratory information systems. The first is cooperation with the hospital information system providing bar-coded label sampling system and test requisition from the information system terminal. The second is real time quality assurance system fully supported from the laboratory information system. The third is random and sequential automated analyzer supported by the bar-code system. In 1994, we set up an automated system in our clinical laboratories. The effect of the quick turnaround service of reporting was analyzed and is discussed herein. Employing this system, the quick turnaround service system was established for 31 items of biochemistry, glucose, Thrombo test and complete cell counting of hematology. Furthermore, these items were available within 30 minutes before medical consultation. Effective sample conveying system, quick sample preparation without clotting and arrival information system of laboratory data as a mailing system are further requirements for this quick turnaround service system.

Clinical Laboratory Information Systems↗

Glutamate uptake blockade induces striatal dopamine release in 6-hydroxydopamine rats with intrastriatal grafts: evidence for host modulation of transplanted dopamine neurons.

The transplantation of fetal dopamine neurons has previously been shown to ameliorate locomotor deficits in laboratory animals with nigrostriatal dopamine lesions. These studies have also demonstrated a reinstatement of striatal dopamine synthesis and release associated with the graft-to-host fiber innervation. More recent studies in the intact striatum indicate that striatal dopamine release can be regulated by corticostriatal glutamatergic projections. In the present study we hypothesized that secretion of dopamine by grafted neurons may also be regulated by similar mechanisms. To test this hypothesis we have measured dopamine release in the striatum of rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway and grafts containing dopamine neurons. Intrastriatal dopamine levels were determined using methods of in vivo microdialysis. The administration of dihydrokainic acid, an inhibitor of glutamate uptake, resulted in the release of striatal dopamine in grafted and normal rats. In contrast, dopamine was not detectable in animals with 6-OHDA lesions alone. Additional studies were conducted to determine the type of glutamate receptor mediating the release of striatal dopamine. Kainic acid administration into the perfusate of the dialysis probe resulted in the release of striatal dopamine in a dose-dependent fashion in both grafted and normal rats. N-methyl-D-aspartate had no effect on dopamine release except at abnormally high concentrations. These results demonstrate that dopamine neurons which are transplanted into the striatum of rats with 6-OHDA lesions become functionally incorporated into the neural circuitry of the host brain, and that the release of dopamine by grafted neurons can be regulated by afferent fibers from the host brain.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

A point mutation at ATP-binding region of the ALD gene in a family with X-linked adrenoleukodystrophy.

A prenatal diagnosis was performed in a family with X-linked adrenoleukodystrophy (ALD). A fetus was at high risk of suffering the disease by segregation analysis and by very long chain fatty acid-CoA synthetase activity assay. A transition (G to A) at codon 617 of the candidate ALD gene was detected by reverse transcription PCR (RT-PCR) based sequencing of the fetal liver RNA. The mutation was located in highly conserved ATP-binding site in this gene and deduced amino acid transversion R617H was thought to be the cause of ALD in this family.

Adenosine Triphosphate↗

Molecular analysis of a patient with Beckwith-Wiedemann syndrome, rhabdomyosarcoma and renal cell carcinoma.

We described a patient with Beckwith-Wiedemann syndrome associated with rhabdomyosarcoma (RMS), and renal cell carcinoma (RCC). Karyotypes of peripheral lymphocytes and RMS cells were normal. DNA analyses showed maternal loss of heterozygosity (LOH) at 11p15 region in RMS but not in RCC. The insulin-like growth factor II gene (IGF2) was found to be expressed at a moderate level in RMS but not in RCC by in situ hybridization. Each of parental allele-derived IGF2 transcript was detected in RCC, while maternal allele-derived transcript was weak in RMS because of maternal LOH. These results suggest that (1) loss of imprinting (LOI) of IGF2 might be responsible for BWS, (2) on the other hand, LOI itself might not induce tumor occurrence in tissues where the control of tissue-specific expression of IGF2 is maintained, (3) increased expression of IGF2 due to maternal loss of a putative controller gene for IGF2 at 11p15 might predispose to sustaining tumorigenic mutations and tumor progression, (4) loss of a putative onco-suppressor gene at 11p15 might induce RMS occurrence. The cause of RCC was thought to be different from that of RMS.

Abdominal Neoplasms↗

Evaluation of monoaminergic neurotransmitters in the rat striatum during varied global cerebral ischemia.

Neurotransmitter release during cerebral ischemia has been extensively studied and is thought to play a key role in excitotoxic neuronal death. The changes in neurotransmitter release and its metabolism may reflect changes in cellular metabolism during ischemia. The purpose of this study is to assess alterations in extracellular dopamine and serotonin and their metabolites under varied degrees of ischemia in rat striatum to elucidate the pathophysiology of cerebral ischemia. Twenty rats were used to induce varied forebrain ischemia by means of bilateral common carotid artery occlusion along with hemorrhagic hypotension. Cerebral blood flow (CBF) in the striatum was measured every 40 minutes by methods of hydrogen clearance and maintained within certain ranges for 6 hours. Dopamine, serotonin, and their metabolites were measured every 20 minutes by in vivo microdialysis. Varying degrees of ischemia were obtained, ranging from 9.4 to 81.3% of control CBF. The animals were divided into three groups according to CBF levels measured 20 minutes after the induction of ischemia. In the mild ischemia group (n = 5), CBF ranged from 65 to 88% of baseline levels and resulted in only a slight increase of dopamine. In the moderate ischemia group (n = 10), CBF ranged from 21 to 48% of baseline levels and resulted in transient increases of dopamine (24-fold) and serotonin (5-fold). In the severe ischemia group (n = 5), CBF was below 14% of baseline levels and resulted in marked increases in dopamine (462-fold) and serotonin (225-fold). These alterations remained elevated for 3 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Purification of a fibroblast-inhibitory factor from Actinobacillus actinomycetemcomitans Y4.

A factor showing inhibitory activity against human gingival fibroblasts was extracted from the cytosol fraction of Actinobacillus actinomycetemocimitans Y4. The activity markedly inhibited the proliferation of human gingival fibroblasts, but had no effect on cell viability or gross morphology. No such activity was found in cytosol fractions from either Porphyromonas gingivalis 381 or Escherichia coli HB101. The extract from A. actinomycetemocomitans Y4 was then purified by anion-exchange chromatography, hydroxyapatite chromatography and gel-filtration chromatography to give a single band on SDS-PAGE with an apparent molecular mass of 65 kDa. The purification ratio was 183-fold with a recovery rate of 5% compared with the crude extract (starting material) when the activity was assessed by direct cell counts.

Actinobacillus↗