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Biomedical subjects

Y Tsuboi

Publications and source records attributed to Y Tsuboi.

At least 55 records · Page 3Linked to original sources

Localization of a novel type trypsin-like serine protease, neurosin, in brain tissues of Alzheimer's disease and Parkinson's disease.

Neurosin, a novel type of trypsin-like serine protease, has been shown to be preferentially expressed in human brain by northern blotting. We examined neurosin immunolabeling in the brains of neurologically normal persons and patients with Alzheimer's disease (AD) and with Parkinson's disease. We also identified the expression of the mRNA for neurosin by in situ hybridization histochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The neurosin antibody stained all of the nuclei of various cell types. In neurons, there was also staining of neuronal cytoplasm, nucleoli and their processes. In AD, staining of neurons with processes was rare in the damaged areas. Some senile plaques, extracellular tangles and Lewy bodies were also positive for neurosin. Expression of the mRNA for neurosin was seen in neurons in the gray matter, and in microglial cells in the white matter. In AD, the intensity of the signal for neurosin mRNA in the gray matter was decreased compared with normal control brains. The relative levels of neurosin mRNA in AD brains, measured by RT-PCR, were lower than those in controls. These results suggest that in human brain neurosin plays various physiological roles, and that in AD this molecule, like other serine proteases, may have a role in the degradation of such substances as beta-amyloid protein.

Aged↗

Outcome of arthroscopic surgery for internal derangement of the temporomandibular joint: long-term results covering 10 years.

OBJECTIVES: To investigate the long-term success (10-year results) of arthroscopic surgery of the temporomandibular joint. PATIENTS AND METHOD: A survey was undertaken of 37 patients who had been treated with arthroscopic surgery for TMJ internal derangement from 1986 to 1990. Thirty-three patients responded, of whom 30 were women and three men, whose age at surgery ranged from 14 to 77 years (mean: 35.1 years). The mean follow-up period was 10 years and 2 months. All patients rated their pain level on a visual analogue scale (VAS), and also recorded pain, jaw dysfunction, and activities of daily living (ADL) before surgery, and at the time of the survey. Interincisal opening was self-assessed (mm). Pre- and postoperative pain, dysfunction and ADL scores were compared for outcome and statistically analyzed with the Student's t-test. RESULTS: Intensity of pain as rated on the VAS was significantly reduced from 5.15 to 0.34 (p<0.01). Pain, dysfunction and ADL scores also decreased from 8.25 to 1.09, 6.5 to 1.93, and 9.1 to 1.32, respectively (p<0.01). At the preoperative examination, 36 of the 37 patients showed limited jaw opening of less than 38 mm, reduced to only three postoperatively. For the success rate of TMJ surgery, the responding 33 plus data of one re-operated patient were assessed. Of these, 27 were rated as excellent, four as good, and three (including two re-operated patients) as poor. The success rate was 83.8% when three patients who did not respond were included in the data. CONCLUSION: The long-term, 10 year outcome of TMJ arthroscopic surgery was considered to be acceptable and stable when compared with other surgical procedures and with the results of previously published middle to long-term treatment outcome studies.

Activities of Daily Living↗

Prolonged mandibular hypomobility patient with a "square mandible" configuration with coronoid process and angle hyperplasia.

The objective of this study was the surgical management of chronic severe mandibular hypomobility patients associated with square mandible morphology with coronoid process and angle hyperplasia, and one-year follow-up data is reported. Ten patients were studied. All patients were female and had a history of gradual severe jaw hypomobility. Clinical findings were similar to those of a "closed lock" patient. However, the facial appearance in these patients showed a characteristic square mandible facial configuration. Coronoid process thickening and overgrowth of the mandibular angle was evident in the radiographic findings. Diagnostic imaging scarcely depicted any disk derangement, but a severely limited jaw opening was noted in spite of acceptable excursive jaw movements. Bilateral coronoidotomy or coronoidectomy was done initially, and then masseter muscle stripping via the intraoral approach. After successful reduction of jaw hypomobility, a selective mandibular anglectomy was completed. Physical therapy began within three to five days after the surgery. Postoperatively, all patients were questioned about their jaw function and their subjective assessment of the treatment. Interincisal jaw opening was recorded with a ruler marked in millimeters. Bilateral coronoidotomy or coronoidectomy and masseter muscle stripping were done for all patients; the mandibular anglectomy was performed in seven of the cases at 13 sites. Simultaneous TMJ surgery was done on three joints for three patients. Most patients reported improvement of jaw function, and the patients' subjective assessment revealed an average satisfaction rate of 74.6%. A preoperative mean jaw opening distance of 25.6 mm increased to 36.6 mm postoperatively at a one-year follow-up (p < 0.05). The conclusion was that surgical intervention is indicated when nonsurgical treatment is unsuccessful. Etiology is unknown, but masseter and temporal muscle contracture associated with mandibular coronoid and angle hyperplasia may be a strong component of the pathophysiology.

Adolescent↗

[Extended spontaneous spinal epidural anterior hematoma over multiple spinal segments. A case report].

We reported a case of extended spontaneous spinal epidural hematoma over multiple spinal segment. A 68-year-old man presented with sudden onset of back pain. He rapidly developed tetraplegia within 15 minutes. On admission, he showed tetraplegia, sensory loss below C4 dermatome, right Horner's sign and bilateral Babinski's signs. These neurological signs gradually improved and disappeared completely within 5 hours. MR imaging showed extended hematoma in the anterior part of spinal epidural space. Spinal angiogram showed no vascular anomaly. The patient had nine years history of antiplatelet therapy, which would produce this episode of the spinal epidural hematoma. The hematoma located in the anterior part of the epidural space and extended over multiple spinal segments was characteristic features in this case. In the case which could have early neurological recovery, conservative therapy might be indicated.

Aged↗

[Progressive cerebellar atrophy following acute antidepressant intoxication].

A 37-year-old woman presented with acute cerebellar atrophy after ingesting toxic doses of tricyclic antidepressants in an attempt of suicide. Two hours after ingestion, she was comatose and showed myoclonus of the limbs, and eventually developed status epileptics. The patient underwent general anesthesia with thiopental, she had hyperpyrexia with elevated muscle enzymes and leukocytosis. These clinical and laboratory features suggested that she had serotonin syndrome (SS). After recovery from coma and hyperpyrexia that had lasted for 7 days, she showed cerebellar ataxia, and progressive cerebellar atrophy of CT scan. As well as neuroleptic malignant syndrome, the SS may cause cerebellar degeneration, probably due to sustained hyperpyrexia.

Adult↗

Melanotransferrin is produced by senile plaque-associated reactive microglia in Alzheimer's disease.

Melanotransferrin (MTf), also known as p97, has been localized in capillary endothelial cells of human brain. In Alzheimer's-diseased (AD) brain tissues, reactive microglial cells located in senile plaques exhibit elevated levels of MTf. The localization of the p97 protein may reflect its site of synthesis or could reflect a paracrine site of action. We examined the expression of MTf mRNA by in situ hybridization histochemistry using AD and healthy brain tissues. We also examined normal liver tissues by immunohistochemistry and in situ hybridization. In all the brain tissues examined, capillaries had positive signals for MTf mRNA. In AD tissues, expression of MTf mRNA appeared in reactive microglial cells in the grey matter specifically associated with dense plaques. In liver tissues, immunohistochemistry using anti-p97 antibody demonstrated that sinusoids were positively stained. In addition, in situ hybridization histochemistry revealed that hepatocytes had positive signals. These results suggest that p97 expression in reactive microglial cells are closely related to AD pathology. These results also support the notion that p97, which appears elevated in the cerebral spinal fluid and serum of AD patients, originates in the reactive microglia associated with dense senile plaques. Thus, p97 is a unique cellular hallmark of AD and further suggests that metal transport mechanisms play a role in this disease.

Aged↗

Glycosylation of microtubule-associated protein tau in Alzheimer's disease brain.

In the neurofibrillary pathology of Alzheimer's disease (AD), neurofibrillary tangles (NFTs) contain paired helical filaments (PHFs) as their major fibrous component. Abnormally hyperphosphorylated, microtubule-associated protein tau is the major protein subunit of PHFs. A recent in vitro study showed that PHF tangles from AD brains are highly glycosylated, whereas no glycan is detected in normal tau. Deglycosylation of PHF tangles converts them into bundles of straight filaments and restores their accessibility to microtubules. We showed that PHF tangles from AD brain tissue were associated with specific glycan molecules by double immunostaining with peroxidase and alkaline phosphatase labeling. Intracellular tangles and dystrophic neurites in a neuritic plaque with abnormally hyperphosphorylated tau, detected with the monoclonal antibodies AT-8 and anti-tau-2, were also positive with lectin Galanthus nivalis agglutinin (GNA) which recognizes both the N- and O-glycosidically linked saccharides. Colocalization was not seen in the extracellular tangles and amyloid deposition, suggesting that the glycosylation of tau might be associated with the early phase of insoluble NFT formation. Thus, although abnormal phosphorylation might promote aggregation of tau and inhibition of the assembly of microtubules, glycosylation mediated by a GNA-positive glycan appears to be responsible for the formation of the PHF structures in vivo.

Alzheimer Disease↗

Failure of cdc2 promoter activation and G(2)/M transition by ANG II and AVP in vascular smooth muscle cells.

The physiological role of the vasoconstrictive hormones arginine vasopressin (AVP) and angiotensin II (ANG II) in the development of vascular hyperplasia is still unclear. We examined the effects of these hormones on cell cycle regulation of cultured rat vascular smooth muscle cells (VSMC). AVP and ANG II were able to induce G(1)/S transition and DNA synthesis in serum-starved quiescent VSMC but failed to promote further progression into G(2)/M phases. AVP and ANG II enhanced the expression and activity of cdk2, cyclin E, and proliferating cell nuclear antigen but did not induce expression of cdc2/cyclin B complex, a critical regulator of G(2)/M transition. The failure of cdc2 mRNA induction was found to be caused by a defect in cdc2 promoter activation. Binding of free E2F-1 to the cdc2 promoter did not occur in hormone-treated VSMC, which may account for the defective induction of cdc2. The absence of cdc2 promoter activation and G(2)/M transition may be important for the prevention of hyperplasia under physiological conditions but underlies the hypertrophy of VSMC.

Angiotensin II↗

Medullary dorsal horn neuronal activity in rats with persistent temporomandibular joint and perioral inflammation.

Studies at spinal levels indicate that peripheral tissue or nerve injury induces a state of hyperexcitability of spinal dorsal horn neurons that participates in the development of persistent pain and hyperalgesia. It has not been demonstrated that persistent injury in the orofacial region leads to a similar state of central hyperexcitability in the trigeminal system. The purpose of the present study was to conduct a parametric analysis of the response properties of nociceptive and nonnociceptive neurons in trigeminal nucleus caudalis (medullary dorsal horn, MDH) in a rat model of persistent orofacial inflammation. Neurons were recorded extracellularly and classified as low-threshold mechanoreceptive (LTM, n = 49), wide dynamic range (WDR, n = 82), and nociceptive-specific (NS, n = 11) neurons according to their response properties to mechanical stimuli applied to their cutaneous receptive fields (RFs). The inflammation was induced 24 h before the recordings by injecting complete Freund's adjuvant (CFA) into the temporomandibular joint (TMJ) capsule or the perioral (PO) skin. The mean areas of the high-threshold RFs of WDR neurons in TMJ (8.66 +/- 0.61 cm(2), n = 25) and PO (5.61 +/- 2.07 cm(2), n = 25) inflamed rats were significantly larger than those in naive rats (1.10 +/- 0. 16 cm(2), n = 32). The mean RF size in TMJ-inflamed rats also was significantly larger than that in PO-inflamed rats (P < 0.01). Furthermore the mean area of the RFs of NS neurons (3.74 +/- 1.44 cm(2), n = 5) was significantly larger in TMJ inflamed rats as compared with naive rats (0.4 +/- 0.09 cm(2), n = 3) (P < 0.05). The background activity in the TMJ- and PO-inflamed rats was generally greater in WDR and NS neurons, but less in LTM neurons, when compared with naive rats. The responses of WDR neurons to noxious mechanical stimuli were increased significantly in TMJ-inflamed rats (P < 0.05) as compared with naive rats. WDR neuronal responses to mechanical stimulation also were increased in PO-inflamed rats but to a lesser extent than in TMJ-inflamed rats. The injection of CFA into the TMJ or PO skin resulted in reduced responses of LTM neurons to mechanical stimuli. The responses of MDH nociceptive neurons to 48-55 degrees C heating were greater in inflamed rats as compared with naive rats. A subpopulation of WDR neurons recorded from TMJ (n = 4 of 10)- or PO (n = 3 of 13)-injected rats responded to cooling in addition to heating of the RFs but did not grade their responses with changes in stimulus intensity. These results indicate that persistent orofacial inflammation produced hyperexcitability of MDH nociceptive neurons. TMJ inflammation resulted in more robust changes in MDH nociceptive neurons as compared with PO inflammation, consistent with previous studies of increased inflammation, increased MDH Fos-protein expression, and increased MDH preprodynorphin mRNA expression in this deep tissue orofacial model of pain and hyperalgesia. The inflammation-induced MDH hyperexcitability may contribute to mechanisms of persistent pain associated with orofacial deep tissue painful conditions.

Animals↗

[Crow-Fukase syndrome associated with Castleman disease showing hypertrophic cranial pachymeningitis and bilateral internal carotid artery occlusion].

A 51-year-old woman was diagnosed as Crow-Fukase syndrome on July 1997, presenting with lymph node swelling, polyneuropathy, hepatomegaly, hypothyroidism, renal dysfunction, edema and skin change. Lymph node swelling and polyneuropathy improved in some degree after chemotherapy. She was admitted to our hospital on march 6, 1998 because of consciousness disturbance, right hemiparesis and non-fluent aphasia after fever and hypotension. The next day of admission, consciousness disturbance, right hemiparesis and non-fluent aphasia disappeared. MR images of the brain revealed low intensity on a T1-weighted image and high intensity on a T2-weighted image in the left parietal lobe. Furthermore, MR images also revealed diffuse hypertrophic dura matter with enhancement by Gd-DTPA, which made the diagnosis of chronic cranial pachymeningitis. The cerebral angiographies showed bilateral internal carotid artery occlusion. The cerebrospinal fluid showed normal cell count, total protein level of 82 mg/dl, and IgG level of 18 mg/dl. Since there has been very few case reports describing intimate relationship between Crow-Fukase syndrome and pachymeningitis, and between carotid occlusion and pachymeningitis, we speculated that the pachymeningitis might be associated with Crow-Fukase syndrome. Furthermore, pachymeningitis might be a cause of her bilateral carotid occlusion. The number of cases of Crow-Fukase syndrome associated with cerebrovascular disease was very rare. This is the first case which had bilateral internal carotid artery occlusion probably caused by chronic cranial pachymeningitis. Therefore, it is necessary to pay attention to cerebrovascular disease when the patient of Crow-Fukase syndrome is associated with pachymeningitis.

Arterial Occlusive Diseases↗

[Subacute necrotizing lymphadenitis associated with mononeuritis multiplex. A case report].

A 20-year-old man noticed lymph node swelling in his neck in May 1997. He was admitted to our hospital on July 30 because of numbness and weakness in the right hand and bilateral lower extremities. Neurological examinations revealed that the patient had right ulnar and bilateral deep peroneal nerve palsies. Nerve conduction study showed severe axonopathy in these nerves. The sural nerve biopsy demonstrated axonal degeneration and thickening of the small arterial wall. There was no significant increase of virus titer in the serum, such as EB virus, nor human herpesvirus 6. CSF examination was normal. During the course of this disorder, he acutely developed severe pain in his right testis. Pathological finding of the testis showed necrosis with vasculitis in the small arteries. Treatment with corticosteroid was effective. Usually subacute necrotizing lymphadenitis has been thought to be a benign disease. Only a few neurological complications, such as aseptic meningitis and cerebellar ataxia have been reported. Mononeuritis multiplex associated with subacute necrotizing lymphadenitis has not been reported. We speculated that the present case initially had some viral infection, and its reaction of the host produced subacute necrotizing lymphadenitis and mononeuritis multiplex.

Adult↗

[Liver transplantation in type II citrullinemia].

We reported a case of adult-onset citrullinemia associated with hypertrigliceridemia and diabetes mellitus. A 24-year-old female was healthy until recently. She first felt intermittent headaches and nausea. Then she noticed memory loss and tiredness. Abnormal behavior such as getting lost on the way from her company sometimes occurred. She came to our hospital because these symptoms had been getting worse. Neurologically she had a very mild disturbed consciousness. An EEG recording showed diffuse slow wave with high amplitude. MR image of the brain showed hyper-intensity in globus pallidus with T1-weighted image. Plasma citrullin level was very high. Plasma ammonia and triglyceride showed a moderately high level. Using biopsied liver tissues, the enzymes of the urea cycle were analyzed. Argininosuccinate synthetase activity was extremely low. Because of clinical course and the result of liver biopsy, the patient was diagnosed as type 2 citrullinemia. A low protein diet was started, but intermittent nausea and consciousness disturbance did not improve. A partial liver transplantation was performed. The living donor was her father, a 50-year-old male, who had normal liver function. After the liver transplantation, all neurological signs soon disappeared. Plasma citrulline, ammonia and triglyceride normalized rapidly. An EEG recording became normal, and the hyper-intensity in globus pallidus with T1-weighted MR image disappeared two months after surgery. Liver transplantation should be planned as soon as possible in a type 2 citrullinemia patient.

Adult↗

White matter astrocytes produce hepatocyte growth factor activator inhibitor in human brain tissues.

Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes and also has multifunctional effects on some other cells in various organs. A HGF activator (HGFA) has been identified as a key enzyme that regulates the activity of HGF in vivo. Our previous studies have shown that brain astrocytes produce both proteins. Recently, HGFA inhibitor-1 (HAI-1), a novel Kunitz-type serine protease inhibitor, has been isolated. We examined HAI-1 immunolabeling in the brains of neurologically normal persons and patients with Alzheimer's disease (AD) and cerebral infarction. Furthermore, we identified the expression of the mRNA for HAI-1 by in situ hybridization histochemistry. The HAI-1 antibody stained astrocytes in the white matter of all brain tissues and was present in plasma. In AD, the intensity of HAI-1 immunolabeling was less than in the other cases. Expression of the mRNA for HAI-1 was also seen in astrocytes. The intensity of the signal for HAI-1 mRNA was similar in AD and normal control brains. These results suggest that, in human brain, secreted pro-HGF from astrocytes may be activated by HGFA and inhibited by HAI-1 on or near the astrocytic cell surface and that rapid HAI-1 consumption may occur in the white matter in AD.

Animals↗

Outcome of arthroscopic surgery to the temporomandibular joint correlates with stage of internal derangement: five-year follow-up study.

We studied the 5-year long-term outcome of arthroscopic surgery, and also investigated whether outcome correlates with stage of internal derangement of the temporomandibular joint (TMJ). A consecutive group of 41 patients (56 joints) who had been followed up for between 3 and 5 years were involved in this study. The result was excellent in 22 patients (54%) and fair in 15 (37%). 7/14 were excellent and 5/14 were fair in stage III, 7/12 were excellent and 4/12 were fair in stage IV, and 8/15 were excellent and 6/15 were fair in stage V. Arthroscopic surgery of the TMJ is an effective and minimally invasive technique for various stages of internal derangement.

Activities of Daily Living↗

Fos protein induction in the medullary dorsal horn and first segment of the spinal cord by tooth-pulp stimulation in cats.

Electrophysiological studies using the single neuron recording technique have led to the hypothesis that nociceptive neurons in the medullary dorsal horn (MDH) and the first segment of the spinal cord (C1) encode the stimulus intensity of noxious stimuli applied to the tooth pulp. The present study utilized the Fos protein technique in combination with electrical and chemical stimulation of the tooth pulp to test this hypothesis. Upper canine tooth-pulp stimulation with intensities just above the threshold stimulus intensity for evoking the jaw-opening reflex (JOR) did not produce a clear expression of Fos protein-like immunoreactive (LI) cells in the MDH and C1 of cats. Fos protein-LI cells were mainly found in the superficial laminae (laminae I-II) of the MDH and C1 after tooth-pulp stimulation of 200% of the JOR threshold intensity. When higher intensities (400-600% of the JOR threshold intensity) or mustard oil were applied, Fos protein-LI cells were also found in laminae III-IV as well as in laminae I-II. The number of Fos protein-LI cells significantly increased when 600% of the JOR threshold intensity or mustard oil was applied. Furthermore, the rostro-caudal distribution of Fos protein-LI cells was greater following increases in stimulus intensities and the greatest after mustard oil application. These data suggest that the change in number and spatial arrangement of nociceptive neurons in the MDH and C1 reflect changes in the encoding of the stimulus intensity applied to the tooth pulp.

Animals↗