Search PubMed⌕ Search

Biomedical subjects

N Iwamoto

Publications and source records attributed to N Iwamoto.

At least 37 records · Page 2Linked to original sources

Molecular characterization of mitotic cyclins in rice plants.

Cyclins are known to activate cyclin-dependent protein kinases, which are essential for cell cycle progression in eukaryotes. We isolated full-length cDNAs encoding rice mitotic cyclins named CycA1; os; 1 and CycB2;os;1, which are related to A- and B-type cyclins, respectively, from animals. To characterize the function of these mitotic cyclins, as well as that of another B-type cyclin, CycB2;os;2, each cDNA was introduced into yeast cells. When cDNAs encoding CycA1;os;1, CycB2;os; or CycB2;os;2 were overexpressed in the yeast mutant DLI, which is deficient in G1 cyclins, the mutant phenotype was rescued, indicating that these mitotic cyclins are functional in yeast cells. When the cDNA encoding CycB2;os;1 was expressed in the wild-type yeast strain, the cells lost the ability to grow, whereas the expression of either cycA1;os: 1 or cycB2;os;2 did not inhibit growth. In situ hybridization of these mitotic cyclin genes with rice root apices and counterstaining of chromosomes with a DNA-specific dye revealed that cycA1;os;1 is expressed from the G2 phase to the early M phase, while transcripts of cycB2:os;1 and cycB2;os;2 accumulated until the end of mitosis. Our results indicate that these B2-type cyclins may be involved in the control of mitosis, in combination with a G2/M-phase CDK.

Amino Acid Sequence↗

Postoperative outcome of 37 patients with lobar intracerebral hemorrhage related to cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Several recent studies have suggested that neurosurgical procedures are not contraindicated in patients with cerebral amyloid angiopathy (CAA). The purpose of this study was to elucidate the clinical factors influencing the outcome of patients with CAA-related intracerebral hemorrhage (ICH) treated surgically. METHODS: A total of 50 neurosurgical procedures (42 intracerebral hematoma evacuations, 4 ventriculoperitoneal shunts, 3 ventricular drainages, and 1 brain biopsy) were performed in 37 patients with CAA-related ICH. To ascertain the clinical factors that may influence their postoperative outcome, their clinical data (demographics, medical history, recurrent lobar hemorrhage, radiographic characteristics, multiple lobar hemorrhage, surgical details, and postoperative hemorrhage) were examined retrospectively and subjected to multivariate analysis. RESULTS: Twenty patients (54%) had a good outcome, and only 4 (11%) died. Parietal hematomas, advanced age (>/=75 years), and intraventricular hemorrhages had significant adverse influence on the postoperative outcome. Clinically significant postoperative hemorrhage requiring evacuation occurred after 2 (5%) of 42 intracerebral hematoma evacuations. Postoperative hemorrhage did not have significant adverse influence on the outcome. CONCLUSIONS: Neurosurgery can be performed relatively safely in patients with CAA-related ICH, and their postoperative outcome is better than that reported previously. Surgical treatment should be considered for such patients aged <75 years without a parietal hematoma and intraventricular hemorrhage.

Age Factors↗

Pyridine nucleotide levels in liver of rats fed clofibrate- or pyrazinamide-containing diets.

Hepatic NAD+, NADH, and NADPH were increased significantly 3 days after feeding rats with a 0.25% clofibrate diet, increased further after 8 days, and stayed at the same levels 14 days after feeding the diet. The NAD+/NADH ratio was decreased significantly by feeding the clofibrate diet for 8 days, while the ratio remained unchanged with a 1% pyrazinamide diet. Hepatic quinolinate phosphoribosyltransferase (QAPRTase) (EC 2.4.2.19) activity was increased to 1.8 and 1.3 times that of the control animals in the clofibrate- and the pyrazinamide-fed rats, respectively, while hepatic aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) (EC 4.1.1.45) activity was decreased to 0 and 19% of that of the control animals. The heat-treated liver homogenate from the pyrazinamide-fed rats contained inhibitory activity toward ACMSDase, while no inhibitory activity was found in the liver homogenate of the clofibrate-fed animals. We conclude that these changes of enzyme activities, which seem due to different mechanisms, may contribute to the increase of pyridine nucleotides in the liver of rats fed clofibrate or pyrazinamide.

Animals↗

Solution structure of Der f 2, the major mite allergen for atopic diseases.

House dust mites cause heavy atopic diseases such as asthma and dermatitis. Among allergens from Dermatophagoides farinae, Der f 2 shows the highest positive rate for atopic patients, but its biological function in mites has been perfectly unknown, as well as the functions of its homologs in human and other animals. We have determined the tertiary structure of Der f 2 by multidimensional nuclear magnetic resonance spectroscopy. Der f 2 was found to be a single-domain protein of immunoglobulin fold, and its structure was the most similar to those of the two regulatory domains of transglutaminase. This fact, binding to the bacterial surface, and other small pieces of information hinted that Der f 2 is related to the innate antibacterial defense system in mites. The immunoglobulin E epitopes are also discussed on the basis of the tertiary structure.

Allergens↗

Glomerular endothelial injury associated with free radical production induced by a fungal cell wall component, (1-->3) beta-D glucan.

Clinical evidence suggests that microangiopathy may be induced by fungal infection. The present study evaluated the toxic effect of (1-->3) beta-D glucan, a major component of fungal cell wall, on cultured transformed glomerular endothelial cells (TF-GEN). When TF-GEN were exposed to increasing concentrations of (1-->3) beta-D glucan (beta-DG; 115 to 430 pg/ml) for 1 to 3 hours, concentration- and time-dependent increases in hydroxyl radical production were demonstrated by electron paramagnetic resonance spectrometry using 5, 5-dimethyl-1-pyrrolyne-N-oxide as a spin trap agent. The amount of radicals induced by 230 or 430 pg/ml beta-DG was comparable to that induced by E. coli LPS (1 or 10 microg/ml). The beta-DG-induced free radical production was associated with a subsequent increase in LDH release from TF-GEN. When TF-GEN pretreated with U78517F (0.1 or 1.0 microM), a lipophilic antioxidant, were stimulated with LPS (1 or 10 microg/ml) or beta-DG (230 pg/ml) for 3 hours, free radical production by TF-GEN was significantly reduced in cells pretreated with the higher concentration of U78517F. Thus, fungal (1-->3) beta-D glucan induces glomerular endothelial injury by stimulating cellular free radical production. Such a mechanism may underlie microangiopathy in systemic fungal infections.

Animals↗

Presence of Vicia graminea lectin- and Vicia unijuga lectin-binding (Vgu) glycoproteins in human fetal membranes and some of their biochemical properties.

We have previously reported that Vicia graminea lectin (VGA)- and Vicia unijuga lectin (VUA)-binding glycoproteins (Vgu glycoproteins), malignant tumor-associated antigens, exist in human meconium and amniotic fluid. To examine the origin of Vgu glycoprotein, their presence, some of their chemical and serological properties and their biosynthesis in the human fetal membrane, amnion and chorion laeve and accompanying membrane cells were examined. Perchloric acid-soluble fractions were prepared from human amnion and chorion laeve, after which VUA-binding components (Vgu glycoproteins) were separated by HPLC and affinity chromatography using immobilized VUA. Biosynthesis of the antigens in primary cultured cells prepared from the amnion and chorion laeve were examined by pulse-labeling and immunoprecipitation using immobilized VUA and compared with those in cultured human cancer cells. The results indicated that the serological properties of VUA-binding components in fetal membranes were similar to those of meconium and amniotic fluid, that many molecular species of VUA-binding components were synthesized in amnion and chorion laeve cells and that about 40-50% of antigens synthesized are secreted from cells while antigens synthesized in cultured cancer cells human were hardly secreted with more than 95% of the antigens remaining in the cells. From these results, we concluded that a large part of Vgu glycoproteins found in amniotic fluid is synthesized in cells of the amnion and chorion laeve and secreted into the fluid, and that Vgu glycoproteins synthesized in cancer cells were not secreted, rather they were retained in the cells.

Amnion↗

[Effects of selegiline hydrochloride on intracellular Ca2+ contents in cultured neuronal cells].

The effects of Selegiline hydrochloride (Selegiline HCl) on the intracellular Ca2+ contents of primarily cultured rat striatal, mesencephalic neuronal cells and PC-12 cells were examined by the use of a Ca2+ imaging analyzer. In the former two cell types, Selegiline HCl (10(-5)-10(-6) M) induced a transient inflow of extracellular Ca2+ through the voltage-dependent N-type Ca2+ channel. In addition, all cells indicating an increase in the intracellular Ca2+ content were found to be catecholaminergic neurons which showed a positive reaction with anti-tyrosine hydroxylase antibodies. Furthermore, a transient intracellular influx of Ca2+ was observed in the NGF-pretreated PC-12 cells. From these results, it is suggested that Selegiline HCl elicits various functions, including antioxidation, activation of neurotrophic factor biosynthesis and neuronal protection probably via an unidentified specific proteins of tyrosine hydroxylase-positive neurons.

Animals↗

Apoptosis resistance of blood cells from patients with paroxysmal nocturnal hemoglobinuria, aplastic anemia, and myelodysplastic syndrome.

Bone marrow (BM) hypoplasia is a major cause of death in paroxysmal nocturnal hemoglobinuria (PNH). However, little is known about the molecular events leading to the hypoplasia. Considering the close pathologic association between PNH and aplastic anemia (AA), it is suggested that a similar mechanism operates in the development of their BM failure. Recent reports have indicated apoptosis-mediated BM suppression in AA. It is thus conceivable that apoptosis also operates to cause BM hypoplasia in PNH. If this is the case, PNH clones need to survive apoptosis and show considerable expansion leading to clinical manifestations. We report here that granulocytes obtained from 11 patients with PNH were apparently less susceptible than those from 20 healthy individuals to both spontaneous apoptosis without any ligands and that induced by anti-FAS (CD95) antibody in vitro. The patients' BM CD34+ cells were also resistant to apoptosis induced by treatment with tumor necrosis factor-alpha, interferon-gamma, and subsequently with anti-FAS antibody. In lymphocytes, the pathologic resistance was not discriminated from inherent resistance to apoptosis. Granulocytes from 13 patients with AA and 12 patients with myelodysplastic syndrome (MDS) exhibited similar resistance to apoptosis. CD34+ cells from MDS-BM also showed similar tendency. Thus, the comparative resistance to apoptosis supports the pathogenic implication of apoptosis in marrow injury of PNH and related stem cell disorders.

Adult↗

First-episode neuroleptic-free schizophrenics: concentrations of monoamines and their metabolites in plasma and their correlations with clinical responses to haloperidol treatment.

Thirty-two first-episode neuroleptic-free schizophrenics were treated with neuroleptics for 8 weeks. The monoamines and their metabolites, dopamine, norepinephrine, serotonin, homovanillic acid (HVA), 3-methoxy-4-hydroxy-phenylglycol(MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) in plasma were measured to examine the association with treatment responses and psychopathology assessed according to the brief psychiatry rating scale (BPRS). No differences were noted in the pretreatment concentrations of monoamines and their metabolites between patients and healthy controls; however, during treatment the concentrations of HVA and MHPG were significantly reduced only in the schizophrenics who responded to treatment. Moreover, the HVA and MHPG reductions correlated significantly with improvements in BPRS scores. Since their plasma levels reflect to some extent central dopaminergic and noradrenergic activities, respectively, the present findings suggest the involvement of these systems in the pathogenesis of schizophrenia as well as the usefulness of such measurements as predictors of responsiveness to neuroleptics.

Adolescent↗

Distribution of apolipoprotein E in senile plaques in brains with Alzheimer's disease: investigation with the confocal laser scan microscope.

In order to elucidate the mechanism of the occurrence of apolipoprotein E (ApoE) in senile plaques (SP) in the brain of Alzheimer's disease (AD) patients, we morphologically examined double immunofluorescent-stained sections by scanning with the confocal laser scan microscope (LSM) and reconstructed their three-dimensional structure by a computerized imaging technique. Brain samples were obtained from six pathologically diagnosed AD patients, including patients with the genotype ApoE epsilon 3/3 and epsilon 4/4 ApoE genotype. We found some clear differences in distribution and shape in the staining patterns of plaque-shaped deposits by ApoE antibody and amyloid beta-protein (A beta) antibody. ApoE deposits were generally larger than A beta deposits in the same region and were distributed widely at the periphery of A beta deposits. Several A beta deposits of typical, compact and primitive plaques were often included in one diffuse plaque-like deposit of ApoE. Some ApoE deposits did not exhibit any A beta-immunoreactivity. Each core represented by ApoE and A beta did not show complete overlap. Typical plaques tended to be composed mainly of A beta-immunoreactivity and had little ApoE-immunoreactivity. The discrepancy between ApoE and A beta deposition may reflect different stages of amyloidogenesis in SP. The presence of ApoE alone in plaques may represent the pathological stage before the beginning of massive A beta deposition.

Aged↗

Distribution of amyloid deposits in the cerebral white matter of the Alzheimer's disease brain: relationship to blood vessels.

The relationship between blood vessels and amyloid beta (A beta)-protein deposits in the cortex of the Alzheimer's disease (AD) brain is still controversial. It is difficult to distinguish whether the A beta deposits are associated with blood vessels or neurons because of their widespread and complicated distribution. In this study, we investigated the distribution of A beta deposits in the cerebral white matter of the AD brain as a means of removing the bias of neuronal distribution. An immunohistochemical study of 100 serial sections, after pretreatment with formic acid for 24 h, revealed the presence of A beta deposits in the cerebral white matter of the AD brain. There are various morphological types of plaques containing A beta deposits in the white matter, the same as in the gray matter. While the majority of A beta deposits was of a circumscribed type such as "classic" and "primitive" plaques, "compact" and "diffuse" plaques were also observed in the white matter. The location of the A beta deposits was, for the most part, immediately beneath the gray matter. The distribution of A beta deposits in the white matter was found to correspond to the orientation of the blood vessels. Serial sections also revealed that these A beta deposits were distributed along a single blood vessel. These findings suggest that the deposition of A beta in the cerebral white matter is primarily related to the blood vessels.

Aged↗

Differential glycosylation of Bence Jones protein and kidney impairment in patients with plasma cell dyscrasia.

Although Bence Jones protein (BJP) is generally accepted to be critically involved in the pathogenic process of kidney impairment in patients with myeloma, patients with BJP do not always have kidney dysfunction. As proteins often undergo glycosylation and alter their molecular nature, it is expected that the heterogeneity in kidney dysfunction can be explained at least partly by the differential affinity to the kidneys of BJP dependent on its glycosylation. Accordingly, we analyzed the structures of carbohydrates of urine BJP biochemically to correlate the structure with kidney function. BJP was obtained from 16 patients with myeloma, 2 patients with light chain amyloidosis, a patient with plasma cell leukemia, and a patient with Waldenstrom's macroglobulinemia. All BJP had five forms of oligosaccharides: three forms of biantennary oligosaccharides and two forms of triantennaries. The three biantennaries correspond to previously reported oligosaccharides on only lambda-type BJP, whereas the triantennaries are novel oligosaccharides found on BJP. Among the five oligosaccharides, the triantennary oligosaccharide Gal(beta)1-4GlcNAc(beta)1-2Man(alpha)1-6 [Gal(beta)1-GlcNA(beta)1-4(Gal(beta)1-4GlcNAc(beta) 1-2)Man(alpha)1-3]Man(beta)1-4GlcNAc(beta)1-4GlcNAc showed a significant negative correlation with the serum creatinine level (p = 0.015 by Spearman's correlation test, R = 0.744). Thus determination of BJP glycosylation may be useful for the evaluation of kidney impairment in patients with BJP.

Bence Jones Protein↗

Down-regulation of manganese-superoxide dismutase gene expression in idiopathic nephrotic syndrome.

An oxidant stress has been shown to prevail in experimental and clinical nephrotic syndrome. Such oxidant stress may be induced by a reduced activity of antioxidant systems. We examined the altered expression of manganese-superoxide dismutase (Mn-SOD), an antioxidant enzyme, in patients with idiopathic nephrotic syndrome, in whom an increased oxidant stress had been demonstrated. The Mn-SOD activities in peripheral blood mononuclear cells obtained from 12 patients with active nephrotic syndrome (6.0 +/- 1.1 years of age, mean +/- SE) and hypoproteinemia were 42% lower (p < 0.05) than in 12 control subjects (5.5 +/- 0.5 years of age) with normal serum total protein concentrations. Reverse-transcriptase polymerase chain reaction also demonstrated that Mn-SOD messenger RNA expression in the patients with nephrotic syndrome was, on average, 59% lower than in control subjects. Because expressions of some genes are sensitive to serum, the serum dependency of Mn-SOD gene transcription was studied in glomerular endothelial cells transfected with a luciferase reporter gene fused with a rat Mn-SOD DNA fragment of -806 to +22 bp of the transcription initiation site (-806:+22). When these cells were exposed to different concentrations of fetal bovine serum (0.5% to 15%), the transcriptional activities determined by luciferase activities were proportional to serum concentrations. This serum-dependent transcriptional activation was also demonstrated by the fragment (-220:+22) but not by the fragment (-220:-20). When glomerular endothelial cells transfected with the fragment (-220:+22) were treated with 5% serum from patients with active nephrotic syndrome, transcriptional activation was more than 80% less than that by 5% serum from control subjects without nephrosis. These results indicate that Mn-SOD gene transcription is regulated at least in part by serum, and that the serum-dependent transcription of the gene is diminished in patients with idiopathic nephrotic syndrome. The regulatory region of serum-dependent gene transcription resides within its early promoter region. Our findings suggest that down-regulation of antioxidant enzyme transcription may contribute increased oxidant stress in idiopathic nephrotic syndrome.

Animals↗

Markedly high plasma erythropoietin and granulocyte-colony stimulating factor levels in patients with paroxysmal nocturnal hemoglobinuria.

In patients with paroxysmal nocturnal hemoglobinuria (PNH), we measured plasma concentrations of endogenous hematopoiesis-regulatory cytokines to characterize bone marrow (BM) hypoplasia which is a major cause of death. Contrary to 10 healthy individuals, all 14 patients with PNH showed increases of erythropoietin (Epo) and granulocyte-colony stimulating factor (G-CSF). There were no signs of infection, renal dysfunction or hypoxia. The lower the hemoglobin level and granulocyte count, the higher the plasma Epo and G-CSF levels. In contrast, marked differences were not found in the levels of interleukin-3 (IL-3), tumor necrosis factor-alpha (TNF-alpha), stem cell factor (SCF), granulocyte/macrophage-colony stimulating factor (GM-CSF), or interferon-gamma) (IF-gamma). The cytokine profiles of PNH patients were quite similar to those of patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). The cytokine profiles may support a pathological relationship between PNH and these stem cell disorders.

Adolescent↗

A magnetic resonance imaging study in first-episode disorganized-type patients with schizophrenia.

Although a number of radiological studies have suggested that brains of patients suffering from schizophrenia have morphological abnormalities, the results are inconsistent. In the present study, in order to examine the brain, morphological features of homogeneous schizophrenics' brain magnetic resonance imagings (MRI) were taken, before neuroleptic treatment, from subjects suffering from disorganized-type schizophrenia, (DOS) during their first episodes. Results showed that DOS had significantly smaller indices for bilateral frontal gray matter (GM), left hippocampal formation (HF), left parahippocampal gray matter (PHGM) and left cingulate gyrus gray matter (CGM) than normal controls. These findings support the previous computed tomography (CT) and MRI studies on schizophrenic brains, although the subjects were not defined as disorganized-type, and may suggest the involvement of a neurocircuit between the bilateral frontal lobe and the left side of limbic system in the first-episode DOS group.

Adolescent↗

Quenching of nitric oxide by an oral carbonaceous adsorbent.

The ability of carbonaceous particles (AST-120), originally developed as an enteral adsorbent of uremic toxins, to quench nitric oxide (NO) was tested. NO in solutions prepared by two methods [NO gas bubbling and NO generating system, i.e., decomposition of 1-hydroxy-2-oxo-3-(aminopropyl)-3-isopropyl-1-triazene] were determined by a NO-specific reduction of carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide using an electron paramagnetic resonance spectrometry. NO concentrations were less in samples containing increasing concentrations of AST-120. In a separate study, nitrite concentrations in lipopolysaccharide-treated RAW264 cells were significantly less in incubation medium containing AST-120. Thus, AST-120 may be applicable as an enteral anti-NO agent.

Adsorption↗

[Clinical results of combination chemotherapy with cisplatin, vinblastine and bleomycin (pvb) for advanced testicular cancer: evaluation of risk criteria].

Between 1982 and 1991, 24 patients with advanced testicular germ cell tumor were treated by combination chemotherapy with cisplatin, vinblastine and bleomycin (PVB). Based on short-term efficacy of the PVB regimen and long-term prognosis in our patients, we evaluated 4 risk criteria proposed by Indiana University, National Cancer Institute (NCI), Memorial Sloan-Kettering Cancer Center (MSKCC) and European Organization for Research and Treatment of Cancer (EORTC). Clinical staging were IIA in 8 patients, IIB in 8, IIIA in 1, IIIB in 5 and IIIC in 2. Metastases included retroperitoneal lymph node in 20 cases (> 5 cm in 10), lung in 6, bone and liver in each 1. Complete response (CR) was obtained in 12 (50%) patients and partial response (PR) in 9 (38%). According to the stage and metastatic site, CR was achieved in 75%, 38% and 38%of the stage IIA, IIB and III tumors, respectively, and in 60% and 50% of retroperitoneal and pulmonary metastases, respectively. However, neither CR nor PR was recognized for live and bone metastases. Prognosis was assessed with a mean followup period of 88.5 months. Although all 12 patients with CR were alive, 4 of the 9 with PR and all patients on whom the drug was ineffective died of cancer. Accuracy in predicting prognosis was 82%, 75%, 74%, and 63% using the MSKCC, Indiana, NCI and EORTC risk criteria, respectively.

Adolescent↗