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Biomedical subjects

A Sakurai

Publications and source records attributed to A Sakurai.

At least 19 recordsLinked to original sources
PubMed2000

The involvement of the neuronal Golgi apparatus and trans-Golgi network in the human olivary hypertrophy.

We studied the Golgi apparatus (GA) and trans-Golgi network (TGN) in the human olivary hypertrophy by immunohistological methods with organelle specific antibodies against the medial cisternae of the organelle (MG160) and the trans-Golgi network (TGN46). The GA and TGN of enlarged neurons in the inferior olivary nuclei in the early stages after central tract lesions lost the normal network-like configuration, and they were reduced to numerous small disconnected granules (fragmentation). In chronic stages after lesions, the GA and TGN of vacuolated or enlarged neurons showed a variety of morphological profiles, such as normal-looking patterns, fragmentation, reduction in number, and aggregation around nuclei or at a distance in the cytoplasm. In patients with multiple system atrophy, the GA and TGN of the neurons in the inferior olivary nuclei showed almost similar findings to those seen in the chronic stages after brainstem lesions. These results suggest that the GA and TGN are affected in degenerating neurons by anterograde transneuronal mechanisms.

Aged↗
PubMed2000

Fragmentation of the Golgi apparatus of the anterior horn cells in patients with familial amyotrophic lateral sclerosis with SOD1 mutations and posterior column involvement.

The Golgi apparatus (GA) of the anterior horn cells in the spinal cord was examined by immunohistological methods with an antibody against the MG-160 protein, a conserved intrinsic membrane sialoglycoprotein of the medial cisternae of the GA, in three patients with familial amyotrophic lateral sclerosis (FALS) with posterior column involvement. Large motor neurons in the anterior horns were markedly reduced in number and 10 of total 14 remaining large motor neurons showed fragmentation and a reduction in the number of the elements of the GA. The fragmentation of the GA was identical to that previously reported in motor neurons of the spinal cord and motor cortex from patients with sporadic ALS and in transgenic mice expressing the G93A mutation of the gene encoding the Cu/Zn superoxide dismutase months before the onset of paralysis. This is the first report of fragmented GA of the anterior horn cells in patients with FALS with posterior column involvement. The findings suggest that the GA is a common target in the neuronal degeneration in sporadic and FALS.

Amino Acid Substitution↗
PubMed2000

Right frontal areas 6 and 8 are associated with simultanapraxia, a subset of motor impersistence.

The authors examined brain lesions that cause simultanapraxia, a subset of motor impersistence. Simultanapraxia was defined as the inability to perform two motor acts simultaneously: closing the eyes and protruding the tongue. Simultanapraxia was found in 9 (5.6%) of 160 hospitalized patients with cerebrovascular diseases. The lesions were located in areas 6 and 8 in the right middle cerebral artery territory. This site was spared in five patients who did not show simultanapraxia, even with a large infarction in the right middle cerebral artery area.

Apraxias↗
PubMed2000

Fragmentation of the Golgi apparatus of the ballooned neurons in patients with corticobasal degeneration and Creutzfeldt-Jakob disease.

We investigated immunohistologically the Golgi apparatus (GA) and the trans-Golgi network (TGN) of the cortical ballooned neurons (BNs) in two patients with corticobasal degeneration and in five with Creutzfeldt-Jakob disease. We observed that the BNs showed fragmentation of the GA and the TGN, accompanied by a reduction in the number of fragmented Golgi elements and by a unique perinuclear distribution. This is the first report of the abnormalities of GA in cortical BNs. These findings suggests that the GA and the TGN may play some roles in the BN formation.

Aged↗
PubMed2000

Enhanced sensitivity to alkylating agent in lymphocytes from patients with multiple endocrine neoplasia type 1.

Chromosome instability is known to be associated with certain autosomal recessive cancer-prone disorders such as Fanconi's anemia. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disorder characterized by development of tumors in two or more endocrine organs, and chromosome instability in patients with MEN 1 has been described. The clinical features of MEN 1 are, however, distinct from other DNA instability syndromes except predisposition to tumors. Therefore, we reevaluated chromosome instability in patients with familial MEN 1. An increase in the frequency of chromosome aberrations was observed in MEN 1 patients but not in control subjects when peripheral mononuclear cells were exposed to an alkylating agent, diepoxybutane (DEB). DEB reduced survival of mononuclear cells in a dose-dependent manner in both MEN 1 patients and control subjects, but this effect was more prominent in MEN I patients. There was no apparent correlation between certain MEN1 gene mutations and sensitivity to DEB. From these results, we conclude that hypersensitivity to alkylating agents exists in patients with MEN 1. Molecular mechanisms of this phenomenon and relationship to tumorigenesis in endocrine organs should be elucidated.

Antineoplastic Agents, Alkylating↗
PubMed2000

Cell-dependent gag mutants of HIV-1 are crucially defective at the stage of uncoating/reverse transcription in non-permissive cells.

We have previously shown that some of the human immunodeficiency virus type 1 (HIV-1) gag matrix (MA), capsid (CA), and nucleocapsid (NC) mutants display host-cell-dependent replication potential, and that they are defective at the early phase of the virus replication cycle in non-permissive cells. To determine the defective replication stage of the cell-dependent mutants precisely, the processes of virus entry into cells and virus DNA synthesis were monitored by the highly sensitive enzyme-linked immunosorbent assay and polymerase chain reaction amplification analysis. The results obtained indicated that all the cell-dependent MA, CA and NC mutants are defective at the stage of uncoating/reverse transcription, and that a cellular factor(s) is involved in this process.

Capsid↗
PubMed2000

Novel deletional mutation of the MEN 1 gene in a kindred with multiple endocrine neoplasia type 1.

MEN1 gene mutation in a Japanese kindred with multiple endocrine neoplasia type 1 was examined. A heterozygous deletion involving 29 base pairs in exon 10 (1606del29) was identified in the proband, and the same deletion was found in the affected family members. Most previously reported germline MEN1 gene mutations are nucleotide substitutions and small insertions/deletions, and a large deletion is rare. The hairpin structure mediated by an incomplete palindromic sequence at deletion termini is the most likely mechanism to be associated with the deletion in the present family.

Adult↗
PubMed2000

Proliferation-associated expression of the MEN1 gene as revealed by in situ hybridization: possible role of the menin as a negative regulator of cell proliferation under DNA damage.

The gene responsible for multiple endocrine neoplasia type 1 (MEN1) has recently been identified. Wide expression of the MEN1 gene in endocrine and non-endocrine organs examined by northern blotting has been reported, but the detailed cellular distribution of the MEN1 transcript in each tissue has not yet been examined in any species. In this report, expression of the MEN1 gene in adult human tissues was studied by in situ hybridization. The MEN1 transcript was widely observed in all tissues examined, and an enhanced expression in relation to cell proliferation was seen in some organs. Cell cycle arrest at the G1-S border reduced the MEN1 mRNA level to less than 50% of that in exponentially growing asynchronous cells. The expression increased as cells entered into S phase, indicating cell cycle-associated transcriptional regulation of the MEN1 gene. Increase or decrease of the amount of menin did not affect proliferation of CHO cells under normal conditions. However, when cells were exposed to the DNA-cross-linking agent, diepoxybutane, overexpression of wild-type menin inhibited DNA synthesis. This effect was not observed when cells were exposed to ultraviolet light. These results suggest that menin may negatively regulate cell cycle under certain DNA damage.

Adult↗
PubMed2000

FDG PET in the evaluation of the aggressiveness of pulmonary adenocarcinoma: correlation with histopathological features.

2-[Fluorine-18]fluoro-2-deoxy-d-glucose (FDG) uptake within the primary lesion correlates with survival on positron emission tomography (PET) studies of patients with non-small cell lung cancer. The more metabolically active the tumour, the worse the outcome. The aim of this study was to determine whether a correlation exists between aggressiveness as determined by pathology and the findings of FDG PET in pulmonary adenocarcinoma. Thirty-five patients with 38 adenocarcinomas of the lung were studied. All patients underwent thoracotomy within 4 weeks of the FDG PET study. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. Patients were classified into high SUV (> or = 4.0) and low SUV (<4.0) groups. The degree of FDG uptake (SUVs) in primary lung lesions was correlated with the histopathological features of aggressiveness (pleural involvement, vascular invasion or lymphatic permeation). The mean SUV of aggressive adenocarcinomas (4.36+/-1.94, n = 22) was higher than that of non-aggressive ones (1.53+/-0.88, n = 16) (P < 0.0001). Tumours with a high FDG uptake have a significantly higher likelihood of aggressiveness than those with a low FDG uptake (P = 0.0004). Analysis by the Kaplan-Meier methods revealed that the groups had different prognoses (log-rank test, P = 0.0099). The high SUV group had a significantly worse prognosis. In conclusion, a correlation was seen between aggressiveness as determined by pathology and glucose metabolism as measured by FDG PET in adenocarcinoma of the lung. FDG PET may be used as a non-invasive diagnostic technique in measuring aggressiveness and prognosis in patients with pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Graded neuromuscular transmission in the heart of the isopod crustacean Ligia exotica.

We present several lines of evidence for the occurrence of graded synaptic transmission in addition to impulse-mediated transmission at the neuromuscular junction between cardiac ganglion (CG) neurones and the myocardium in the isopod crustacean Ligia exotica. In the heart of adult Ligia exotica, the CG acts as a primary pacemaker for the heartbeat by generating periodic bursts of impulses and entrains the myogenicity of the myocardium via impulse-mediated excitatory junctional potentials. When impulse generation was blocked by tetrodotoxin (TTX; 50 nmol l(-)(1)), the CG neurones and the myocardium periodically exhibited synchronized slow depolarizing potentials. The association between the slow depolarizing potentials in the neurone and the myocardium was eliminated by application of Joro spider toxin (JSTX), a specific glutamate antagonist. When the CG neurone was made quiescent by a higher dose of TTX (1.0 micromol l(-)(1)), sinusoidal current injected into the CG neurone induced similar sinusoidal membrane potential responses in the myocardium. The sinusoidal muscle responses were eliminated by application of either JSTX or low-Ca(2+) saline. Under voltage-clamp conditions, the myocardium exhibited periodic inward current responses to sinusoidal current stimuli applied to the CG neurone. The reversal potential for the current response of the myocardium was similar to that of the impulse-mediated excitatory junctional current (EJC). Extracellular macropatch recordings of EJCs made at the neuromuscular junctional site revealed the spontaneous appearance of miniature EJCs asynchronous with the CG spikes in addition to large spike-evoked EJCs. The miniature EJCs were present in saline containing TTX, and their frequency was strongly affected by the slow membrane potential change in the CG neurone. These results suggest that the CG neurones drive the myocardium by graded neuromuscular transmission in addition to impulse-mediated transmission in the heart of Ligia exotica.

Animals↗
PubMed2000

Chromogranin A expression in hepatocellular carcinoma in a patient with germline MEN1 gene mutation.

Hepatocellular carcinoma (HCC) was found in a patient with multiple endocrine neoplasia type 1 (MEN 1). The intriguing finding was that the HCC in the patient was positively stained for chromogranin A (CgA), a cellular marker for endocrine and neuroendocrine tumors. The patient had a pancreas endocrine tumor and type C hepatitis, that made pathological diagnosis of the origin of the tumor complicated.

Carcinoma, Hepatocellular↗
PubMed2000

Mutational analysis of HIV-1 gag proteins (review).

The mature Gag proteins of human immunodeficiency virus type 1 (HIV-1) are major components of infectious virions, and thought to carry out numerous functions throughout the HIV-1 replication cycle. We have recently generated numerous gag gene mutants of HIV-1 to genetically study the functions of the Gag proteins. Through the biological and biochemical analyses, our HIV-1 gag mutants have been grouped into early (defective for uncoating/reverse transcription), late (defective for virion release/maturation), and early/late (defective for both steps) mutants. Many mutants are found to efficiently inhibit the replication of wild-type virus. Worthy of note, there are some early mutants which show host cell-dependent replication potential.

DNA Mutational Analysis↗
PubMed2000

FDG PET measurement of the proliferative potential of non-small cell lung cancer.

UNLABELLED: The goals of this study were to correlate FDG uptake with cell proliferation and cellular density in non-small cell lung cancer. METHODS: Thirty-one patients with 32 non-small cell lung cancers were examined with FDG PET. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. All patients underwent thoracotomy within 4 wk after the FDG PET study. Cell proliferation was immunohistochemically assessed as the relative number of cells expressing the proliferating cell nuclear antigen ([PCNA] labeling index). Cellular density was also evaluated using light microscopy. RESULTS: SUVs correlated significantly with PCNA labeling index (r = 0.740; P < 0.0001) but only weakly with cellular density (r = 0.392; P = 0.0266). High FDG uptake correlated with high PCNA expression. The PCNA labeling index and SUVs were significantly lower in bronchioloalveolar carcinomas (n = 8) (12.3 +/- 9.45% and 1.45 +/- 0.76, respectively) than in nonbronchioloalveolar carcinomas (n = 19) (33.5 +/- 21.8%, P = 0.015, and 3.75 +/- 1.93, P = 0.003, respectively). However, no significant differences in cellular density were seen between bronchioloalveolar carcinomas and nonbronchioloalveolar carcinomas. CONCLUSION: FDG uptake is related to cell proliferation rather than to the cellular density of non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

MHC-I expression in HTLV-1-positive and -negative cells.

The expression level of major histocompatibility class I (MHC-I) and the extent of down-regulation of MHC-I after an anti-MHC-I antibody treatment in numerous human T-cell leukemia virus type 1 (HTLV-1)-positive and -negative lymphocytic cell lines were examined. While there was no clear correlation between the expression level of MHC-I and the presence of HTLV-1 genome, a relatively low level of MHC-I down-regulation was generally induced in HTLV-1-positive cells by the antibody. The results may suggest the potential involvement of MHC-I in HTLV-1 leukemogenesis.

Antibodies, Monoclonal↗
PubMed2000

[Use of percutaneous cardiopulmonary support (PCPS) for extended surgery in patients with T4 tumor].

Since 1991, we have performed operations for tumors invading the upper airway, left atrium or main pulmonary artery with percutaneous cardiopulmonary support (PCPS) stand by support available. Of 15 cases with PCPS stand by, 6 patients actually underwent operation using PCPS. There were three esophageal cancers invading the carina, two lung neoplasms with left atrial invasion and one neoplasm extending to the main pulmonary artery. One of three patients with esophageal cancer had massive bleeding in the trachea resulting in airway obstruction. For this patient, emergency PCPS was carried out followed by the total removal of the thoracic esophagus and combined resection of membranous portion of the carina. As a result, a substantial amount of time (6 hours) was required. The two patients with reconstruction of the carina due to esophageal cancer were also successfully treated by using PCPS. Two patients with malignant pulmonary neoplasms invading the left atrium underwent combined resection of the lung and left atrium using a combination of PCPS and ventricular fibrillation under normothermia. In conclusion, PCPS should be accepted as a standard technique for patients with advanced thoracic malignancies in whom cardiac arrest or ventilation support is thought to be necessary for the complete removal of the tumor.

Adult↗
PubMed1999

Regulatory role of metallothionein in NF-kappaB activation.

Metallothionein (MT), a low molecular weight, cysteine-rich metal binding protein, has been associated with cytoprotection from heavy metals and cellular oxidants. As MT has the ability to scavenge hydroxyl radicals, MT may control intracellular redox status. In the present study, we examined whether MT regulates the activity of nuclear factor-kappaB (NF-kappaB), which is one of the redox-regulated transcription factors, using the MT null embryonic cell lines established from MT null mice. We first found that tumor necrosis factor (TNF)-induced activation of the binding of NF-kappaB protein to DNA in wild type MT+/+ cells was lower than that in MT-/- cells. The NF-kappaB activation in MT-expressing cells established from MT-/- cells by the transfection of mouse MT-1 gene was also significantly lower than that in MT-/- cells. In addition, transfection of the MT gene inhibited TNF-induced IkappaB degradation and suppressed NF-kappaB-dependent gene expression induced by TNF. These results demonstrate that MT may function as a negative regulator of NF-kappaB activity.

Animals↗
PubMed1999

Fragmentation of the Golgi apparatus of Betz cells in patients with amyotrophic lateral sclerosis.

The Golgi apparatus (GA) of the large pyramidal motor neurons in the cerebral cortex (Betz cells), was examined in sixteen patients with sporadic amyotrophic lateral sclerosis (ALS), in one patient with familial ALS (FALS), and in ten non-ALS age matched controls including one patient with Huntington's disease and one patient with a brain infarct. The GA was immunostained with an antibody against the MG-160 protein, a conserved sialoglycoprotein of the medial cisternae of the organelle. In ALS, 13.2% of counted Betz cells had fragmented GA in contrast to 0.6% in the ten non-ALS controls. The fragmentation of the GA of Betz cells was identical to that previously reported in spinal cord motor neurons from patients with sporadic ALS and in transgenic mice expressing the G93A mutation of the gene encoding the Cu/Zn superoxide dismutase. The striking morphological similarity between the fragmentation of the GA observed in Betz cells and in spinal cord motor neurons suggests that a similar pathogenic mechanism is responsible for both, and that the fragmentation of the GA of the spinal cord motor neurons is not a consequence of deafferentation due to the degeneration of the Betz cells.

Adult↗