Biomedical subjects

M Yamada

Publications and source records attributed to M Yamada.

At least 649 records · Page 36Linked to original sources

PubMed1998

Hereditary dentatorubral-pallidoluysian atrophy: ubiquitinated filamentous inclusions in the cerebellar dentate nucleus neurons.

We examined the cerebellar dentate nucleus (CDN) in 16 patients with hereditary dentatorubral-pallidoluysian atrophy (DRPLA), one of the neurodegenerative diseases caused by expansion of a CAG repeat encoding a polyglutamine tract in the disease protein. In all patients, some CDN neurons were found to contain ubiquitinated filamentous inclusions in their cytoplasm. On hematoxylin and eosin preparations, these filamentous inclusions were eosinophilic, basophilic or amphophilic, and were often found in areas of pale cytoplasm. Electron microscopy revealed that they consisted of bundles of filaments that were somewhat thicker than neurofilaments. These features of the present inclusions were indistinguishable from those of skein-like inclusions (SLI) previously described in the lower motor neurons in sporadic amyotrophic lateral sclerosis. We conclude that SLI can also occur in the CDN in DRPLA and believe that they reflect a characteristic pathological process in this disease.

Adolescent↗

PubMed1998

Accumulation of alpha-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy.

Recently, we have shown that the precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP), also known as alpha-synuclein, is a major component of Lewy bodies (LBs) as well as neuronal and glial cytoplasmic inclusions in multiple system atrophy (MSA). To elucidate whether the accumulation of NACP is specific to LB disease and MSA, we further studied 83 autopsied cases with various neurological disorders, using anti-NACP antibodies. In LB disease, NACP immunoreactivity was present in all of the LBs and Lewy neurites in both the central and peripheral nervous systems, the pale bodies in the substantia nigra, and dystrophic neurites in the hippocampal CA2/3 region. Immunoelectron microscopy revealed that the reaction product was localized within filamentous structures and associated granular structures. In MSA, NACP immunoreactivity was found in the intracytoplasmic inclusions of both neuronal and oligodendroglial cells, neuronal intranuclear inclusions, and swollen neuronal processes. No NACP immunoreactivity was found in a variety of other neuronal or glial inclusions in other disorders, including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, motor neuron disease and triplet-repeat diseases. These findings strongly suggest that the accumulation of NACP is a cytopathological feature common to LB disease and MSA.

Cellular Senescence↗

PubMed1998

Hereditary dentatorubral-pallidoluysian atrophy: detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain.

We examined the brains and spinal cords of seven patients with clinicopathologically and genetically confirmed hereditary dentatorubral-pallidoluysian atrophy (DRPLA) using an antibody against ubiquitin, and found small, round immunoreactive intranuclear inclusions in both neurons and glial cells in various brain regions. Ubiquitinated neuronal intranuclear inclusions (uNIIs) were consistently found in the striatum, the pontine nuclei, the inferior olivary complex, the cerebellar cortex and the dentate nucleus. Ubiquitinated glial intranuclear inclusions (uGIIs) were found less frequently than uNIIs. Most of the inclusion-bearing nuclei were of an astrocytic nature. Immunostaining with an antibody against DRPLA protein revealed similar immunoreactive neuronal and glial intranuclear inclusions, but in much smaller in numbers compared with uNIIs and uGIIs. Electron microscopy showed that such inclusions were composed of granular and filamentous structures. These findings strongly suggest that, in DRPLA, the occurrence of uNIIs and uGIIs is directly related to the causative gene abnormality (an expanded CAG repeat encoding polyglutamine), that neurons are affected much more widely than previously recognized and that glial cells are also involved in the disease process.

Adult↗

PubMed1998

Preeclampsia with fetal death in a patient with schistosomiasis japonica.

A case of preeclampsia with fetal death at 32 weeks' gestation is reported. Liver examination of the patient revealed network patterns on ultrasonography and linear calcifications on unenhanced CT scans in the liver. These findings are typical of those of chronic schistosomal infection. Indeed, liver biopsy specimens showed eggs of schistosoma japonicum. We diagnosed her case as preeclampsia with liver cirrhosis due to chronic schistosomiasis japonica. Schistosomal placentitis may have been present and may have contributed to preeclampsia and fetal death.

Adult↗

PubMed1998

The effects of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K+ channel expressed in a mammalian cell line, HEK293T cells.

The effects of potassium channel opening drugs and intracellular nucleotides on the ATP-sensitive K+ (KATP) channel composed of SUR2A and Kir6.2 in HEK293T cells were examined using the patch-clamp technique. The SUR2A/Kir6.2 channel was activated effectively by pinacidil, marginally by nicorandil but not by diazoxide. The pinacidil-activated channel currents were inhibited by glibenclamide with a Ki value of 160 nM. Upon formation of inside-out (I-O) patches, spontaneous openings of the channels appeared, which were inhibited by intracellular ATP (ATPi) equipotently in the presence and in the absence of intracellular Mg2+ (Mg2+i). The channel activity ran-down gradually in I-O patches. The run-down channels could be reactivated by ATPi only in the presence of Mg2+i. Uridine 5'-diphosphate (UDP) antagonized the ATPi-mediated inhibition of the channel activity before run-down. After run-down, UDP activated the channel without antagonizing ATPi-mediated channel inhibition. Thus, the SUR2A/Kir6.2 reproduced the major properties of the native cardiac KATP channel well in terms of nucleotide regulation and pharmacology, and therefore can be a useful tool with which to elucidate the molecular mechanisms characterizing the KATP channel.

ATP-Binding Cassette Transporters↗

PubMed1998

Gastric antral vascular ectasia successfully treated by endoscopic electrocoagulation.

We report two cirrhotic patients with gastric antral vascular ectasia (GAVE) in whom chronic blood loss presented a major problem. Case 1, a 69-year-old man, had alcoholic liver cirrhosis, and case 2, a 75-year-old woman, had liver cirrhosis associated with hepatitis C virus. The patients required repeated blood transfusions but still exhibited persistent anemia. On upper gastrointestinal endoscopy, both patients showed esophageal varices without stigmata of bleeding or red color signs and presented with a characteristic antral appearance so distinctive as to be diagnostic; diffuse erythemas consisting of ectatic and tortuous capillaries throughout the antrum. Endoscopic electrocoagulation treatment with a monopolar probe was effective for controlling blood loss from GAVE. The patients tolerated the procedure well and there were no resultant complications. Several sessions of the treatment resulted in eradication of almost all the vascular lesions, negative fecal occult blood test results, and marked alleviation of their anemia without further treatment. Endoscopic electrocoagulation is suggested to be a safe, non-invasive, and effective treatment for blood loss from GAVE, especially in patients with liver cirrhosis in whom surgery carries an increased risk.

Aged↗

PubMed1998

Intrameatal tumours presenting as a hearing disturbance: case reports of meningioma and lymphoma.

This paper presents two patients with chronic progressive hearing disturbance. Each patients had an intrameatal tumour, part of which extended to the cerebellopontine (CP) angle. In both cases, the patients were initially diagnosed with an acoustic neurinoma. A 63-year-old male experienced a hearing disturbance in the left ear for 1.5 years prior to visiting our hospital. Magnetic resonance (MR) imaging revealed a mass which was surgically resected. The tumour originated from the intrameatal dura mater. Histologically, the tumour was a meningioma. Similarly, a 53-year-old male presented with systemic lymphoma diagnosed 10 months earlier, and a hearing disturbance in the right ear that began 3 months prior to visiting our hospital. MR imaging prior to chemotherapy revealed a mass which extended to the CP angle. Part of the tumour in the CP angle disappeared after chemotherapy, suggesting a secondary lymphoma. Another tumour appeared later in Meckel's cave on the left side; however, it decreased in size following repeated chemotherapy. The present results indicate that differential diagnosis of intrameatal tumours and acoustic neurinomas may be difficult due to the small tumour size. Recent progress in neuroradiology may allow distinction of intrameatal tumours as a separate tumour classification. Our second patient is the sixth reported case of a CP angle lymphoma in the literature.

Diagnosis, Differential↗

PubMed1998

The classic form of granular corneal dystrophy associated with R555W mutation in the BIGH3 gene is rare in Japanese patients.

PURPOSE: To identify the BIGH3 gene mutation in 10 unrelated Japanese individuals with granular corneal dystrophy. METHODS: Genomic DNA was obtained from each patient's leukocytes. Exons 4 and 12 of the BIGH3 gene were amplified by polymerase chain reaction and were directly sequenced. RESULTS: Nine of these patients were found to have the R124H mutation, whereas only one had the R555W mutation. Slit-lamp examination showed that the granular corneal dystrophy associated with each mutation is different. CONCLUSIONS: These results, together with our previous findings, show that the classic form of granular corneal dystrophy associated with the R555W mutation is rare in Japanese patients, whereas granular corneal dystrophy accompanied by amyloid deposits and associated with the R124H mutation, Avellino corneal dystrophy, is more common. Direct examination may be insufficient in the proper diagnosis of corneal dystrophy, and BIGH3 mutation analysis may be required.

Adult↗

PubMed1998

Corneal ulcer associated with deposits of norfloxacin.

PURPOSE: To report a case of corneal ulcer associated with deposits of norfloxacin. METHOD: Case report. A 40-year-old man with right trigeminal and facial nerve palsies and decreased tear secretion developed a corneal ulcer with white deposits in the right eye. The deposits were removed and analyzed by high-performance liquid chromatography. RESULTS: High-performance liquid chromatography results disclosed that the deposits on the corneal surface had the same retention time as norfloxacin. The patient discontinued norfloxacin ophthalmic solution and recovered successfully. CONCLUSION: Clinicians should be aware that frequent applications of topical norfloxacin in patients with decreased tear secretion may result in deposition of the drug on the cornea.

Adult↗

PubMed1998

Histopathological and immunohistochemical studies of intracranial nervous-system tumours in four cattle.

Intracranial nervous-system tumours were diagnosed in three of 1092 bovine necropsy specimens submitted to the Department of Veterinary Pathology, Obihiro University between April 1983 and March 1996. A fourth case was a referral from the Department of Veterinary Pathology, Rakuno Gakuen University. Histopathological examination revealed four types of tumour: intracranial malignant peripheral nerve sheath tumour (MPNST), choroid plexus papilloma, differentiated fibrillary astrocytoma and anaplastic (malignant) astrocytoma. Immunohistochemically, the intracranial MPNST was strongly positive for S-100 protein and vimentin, and in places weakly positive for glial fibrillary acid protein (GFAP). The choroid plexus papilloma was strongly positive for epithelial membrane antigen (EMA), keratin, S-100 protein and vimentin, and positive for GFAP in places. The cytoplasm and fibrous component in the differentiated fibrillary astrocytoma were strongly positive for S-100 protein and GFAP. The anaplastic (malignant) astrocytoma was strongly positive for vimentin, S-100 protein and keratin in the cytoplasm and fibrous processes, and weakly positive for GFAP and EMA in places. Myelin basic protein (MBP) and synaptophysin showed a weak positive reaction in the marginal areas of the tumour.

Animals↗

PubMed1998

Inhibition of tumor necrosis factor-alpha production by SK&F 98625, a CoA-independent transacylase inhibitor, in cultured rat peritoneal macrophages.

When rat peritoneal macrophages were incubated in medium containing thapsigargin, tumor necrosis factor-alpha (TNF-alpha) production was increased time-dependently. In the presence of SK&F 98625, a CoA-independent transacylase inhibitor, the thapsigargin-induced TNF-alpha production was inhibited dose-dependently. Platelet-activating factor (PAF) and prostaglandin E2 (PGE2) production were also inhibited by SK&F 98625. The SK&F 98625-induced inhibition of TNF-alpha production was not prevented by addition of PGE2. PAF antagonists such as E6123, L-652,731 and CV-6209 partially inhibited the thapsigargin-induced TNF-alpha production, suggesting that concurrently produced PAF in thapsigargin-stimulated macrophages up-regulates TNF-alpha production. The inhibition by SK&F 98625 of thapsigargin-induced TNF-alpha production might be partly due to the inhibition of PAF production.

Acyltransferases↗

PubMed1998

Distinct functional characteristics of levocabastine sensitive rat neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

Neurotensin has been shown to produce pharmacological effects both in brain and periphery. Several of these effects are mediated by a high-affinity neurotensin NT1 receptor. On the other hand, a low-affinity levocabastine-sensitive neurotensin NT2 receptor was molecularly cloned from rodent brain recently. In this study, in contrast to NT1 receptor, levocabastine (a histamine H1 receptor antagonist) and SR48692 (an antagonist for NT1 receptor) strongly stimulated intracellular Ca2+ mobilization in transfected Chinese hamster ovary cells expressing rat NT2 receptor, thus acting as potent NT2 receptor. Furthermore, despite of their affinities for NT2 receptor, the Ca2+ responses to potent NT1 agonists, neurotensin or JMV449 ([Lys8-(CH2NH)-Lys9]Pro-Tyr-Ile-Leu, a peptidase resistant analogue of neurotensin) were much smaller than that observed with SR48692. These findings suggest that NT1 and NT2 receptors present distinct functional characteristics and that SR48692 may act as a potent agonist for NT2 receptor.

Animals↗

PubMed1998

The significance of retrograde thrombosis following removal of arteriovenous malformations in elderly patients.

BACKGROUND: Retrograde thrombosis of former feeding arteries should be considered as a distinct postoperative complication following surgery for arteriovenous malformation (AVM). Regardless of the presence of AVMs, the cerebral arteries undergo atherosclerotic changes with advancing age. In the present study, three cases in elderly patients who developed retrograde thrombosis are reported, and the effect of the patient's age on this complication is discussed. CLINICAL MATERIALS AND METHODS: The present study group consisted of 158 patients who underwent AVM resection and postoperative angiographic studies. Five patients were 65 years of age or older (elderly group) at the time of operation, 108 were between 20 and 64 years of age (adult group), and 45 were less than 20 years of age (young group). The incidence of retrograde thrombosis in the elderly group was compared with that of the other two groups. RESULTS: We found that surgery in the elderly group was accompanied by a significantly higher incidence of retrograde thrombosis (60%) than in the adult group (4%), or the young group (0%). CONCLUSIONS: The present study suggests that this complication should be considered as a serious possibility following removal of an AVM, especially in elderly patients.

Adult↗

PubMed1998

Effects of cumulus cell density during in vitro maturation of the developmental competence of bovine oocytes.

To determine the role of cumulus cells in oocyte maturation, we carried out an investigation on the effects of addition of cumulus cells to the maturation medium on the developmental competence of corona-enclosed oocytes and oocytes denuded from their somatic cells. The addition of cumulus cell (1.6 x 10(6) cells/mL) improved the development of bovine corona-enclosed oocytes, however, addition of a similar number of cumulus cells as cumulus-oocyte-complexes (COCs, cumulus cell density: 4.2 x 10(6) cells/mL) had no effect on the development of oocytes denuded from their somatic cells. To determine if corona-enclosed oocytes can obtain developmental competence without the addition of extra cumulus cells, the effects of cell density during in vitro maturation on the developmental competence were studied. A density of 1.6 to 3.2 x 10(6) cumulus cells/mL was the most effective for in vitro maturation of oocytes with intact gap junctions. The effects of the medium conditioned by COCs on the developmental competence of oocytes was also examined. It was demonstrated that COC-conditioned medium improved the development of bovine oocytes to the blastocyst stage. These data suggest that the developmental competence of bovine oocytes surrounded with corona cells is supported in a cell density-dependent manner in the maturation medium. In addition, the data indicate that cumulus cells benefit bovine oocyte development either by secreting soluble factors which induce developmental competence or by removing an embryo development-suppressive component from the medium.

Animals↗

PubMed1998

Effects of antioxidants on the development of bovine IVM/IVF embryos in various concentrations of glucose.

This study was undertaken to determine the effects of glucose, antioxidants and different oxygen tensions on the development of bovine embryos cultured in modified synthetic oviduct fluid (m-SOF) medium. In vitro matured (IVM) and fertilized (IVF) oocytes were incubated for 48 h. Embryos reaching at least the 4-cell stage were selected for further culture under various conditions for 6 d. Supplementing the m-SOF media with 4.5 mM glucose resulted in a significantly lower (P < 0.01) embryo developmental rate (21%; Day 8) than was obtained with 1.5 mM glucose (58%; Day 8) or no glucose (53%; Day 8). Antioxidants such as SOD, catalase and mannitol had no positive effect on embryo development in m-SOF medium supplemented with 1.5 mM glucose. However, in m-SOF medium supplemented with 4.5 mM glucose, SOD and mannitol significantly (P < 0.05) improved embryo development: SOD increased the developmental rate from 19 to 35% (Day 8), while mannitol increased it from 13 to 30% (Day 8). Low oxygen concentration improved embryo development significantly (P < 0.05) in m-SOF medium supplemented with 4.5 mM glucose (low O2: 31% vs high O2: 14%; Day 8) but not 0 mM glucose (low O2: 58% vs high O2: 55%; Day 8). Our data suggest that low concentration of glucose during culture of bovine embryos is beneficial, and that generation of free oxygen radicals is partly caused by a high concentration of glucose in the medium.

Animals↗

PubMed1998

Anti-arthritic effects of the novel dipeptidyl peptidase IV inhibitors TMC-2A and TSL-225.

We evaluated the immunopharmacological effects of two novel dipeptidyl peptidase IV (DP IV) inhibitors, TMC-2A [(2S,2S',2S'')-2-[2'-[2''-amino-3''-(-indol-3'''-yl)-1''-oxopropyl]-1',2 ',3',4'-tetrahydro-6',8'-dihydroxy-7'-methoxyisoquinol-3-yl-car bonylamino]-4-hydroxymethyl-5-hydroxypentanoic acid] and TSL-225 (tryptophyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid). TMC-2A, produced by Aspergillus sp. A374, inhibited rat kidney DP IV uncompetitively, with a Ki value of 5.3 microM. In vivo, TMC-2A suppressed alkyldiamine (N,N-dioctadecyl-N',N-bis(2-hydroxyethyl)propanediamine)-induced arthritis. We developed a chemically modified inhibitor, TSL-225, with potency similar to that of TMC-2A. TSL-225 inhibited DP IV uncompetitively, with a Ki value of 3.6 microM. TSL-225 was also effective against adjuvant-induced arthritis. These results suggest that TMC-2A and its derivatives may have therapeutic potential for the treatment of inflammatory diseases such as rheumatoid arthritis.

Adjuvants, Immunologic↗

PubMed1998

Elevation of serum IgE level and peripheral eosinophil count during T lymphocyte-directed gene therapy for ADA deficiency: implication of Tc2-like cells after gene transduction procedure.

We have successfully carried out T-cell-directed gene therapy for a boy with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA SCID) and unexpectedly found an elevation of serum IgE level and peripheral eosinophil count during the course. More than 90% of transduced cells cultured for 7-11 days before infusion into the patient were positive for CD8 and expressed Th2-type cytokine genes such as IL-4, IL-5 and IL-13. Furthermore, CD4(+) T-depleted PBMC (peripheral blood mononuclear cells) from the patient synthesized IgE in vitro by stimulation with IL-4. Collectively, these results suggested that Tc2-like cells in the transduced cells have distinct immunological functions to help IgE synthesis and activate eosinophils.

Adenosine Deaminase↗

PubMed1998

Development of a dot blot neutralizing assay for HHV-6 and HHV-7 using specific monoclonal antibodies.

To elucidate further immune responses to human herpesviruses 6 and 7 (HHV-6 and -7), a neutralizing antibody assay was established for these viruses using a dot blot method. Three monoclonal antibodies against HHV-6 and 12 monoclonal antibodies against HHV-7 were developed and characterized by radio-immunoprecipitation. One monoclonal antibody which recognizes the 135 kDa late polypeptide of HHV-6 and several which recognize the 125 kDa late polypeptide of HHV-7 were selected to monitor virus growth by a dot blot antigen-detection method. The dot blot method was then used for the assay of HHV-6 and -7 neutralizing antibodies in human serum samples. The neutralization endpoints determined by the dot blot were comparable to those determined by immunofluorescence (IF). The neutralizing antibody titers appeared to correlate with the antibody titers determined by the indirect IF antibody test. The dot blot neutralization assay is easy to perform, is highly reproducible and objective when compared with the conventional methods based on cytopathology or IF for determining neutralization endpoints.

Animals↗