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Biomedical subjects

T Itoh

Publications and source records attributed to T Itoh.

At least 469 records · Page 26Linked to original sources

[Pulmonary function at the early stage after bone marrow transplantation].

Twenty-one patients, aged 16-41 years, were prospectively followed for pulmonary function prior to and up to nine months after bone marrow transplantation (BMT). All patients had normal radiographs and no clinical signs of pulmonary disease. The FEV1.0%, V25, and of V50/V25 were within the normal ranges for all patients. Percent vital capacity (%VC) and percent diffusing capacity of lung for CO (% DLco) dropped progressively in most of the patients up to 9 months following BMT. Pulmonary function decreased earlier in patients with GVHD as well as patients who received total body irradiation either at a high dose rate (10 cGy/min) or a high lung dose (12 Gy). These asymptomatic declines in pulmonary function were measured by frequent tests of lung function.

Adolescent↗

[Malignant lymphoma occurring in a patient with neurofibromatosis type 1 (von Recklinghausen disease)].

Malignant lymphoma developed in a 65-year-old man with type 1 neurofibromatosis (von Recklinghausen disease). The patient visited the hospital for evaluation of generalized lymphadenopathy. A physical examination discovered café au lait spots, neurofibromas, and generalized enlargement of the superficial lymph nodes. A computed tomogram demonstrated enlarged mediastinal and para-aortic lymph nodes in the abdomen. Biopsy specimens from the right side of the patient's neck were examined, and a diagnosis of non-Hodgkin's lymphoma (diffuse mixed type, T cell type) was made. Although the patient achieved a partial response with combination chemotherapy, he died of pneumonia. Cases of malignant lymphoma associated with type 1 neurofibromatosis are rare in the literature.

Aged↗

[Tay-Sachs disease].

Explore the source record for details and available documents.

Central Nervous System↗

Isoprenoid synthesis gene for geranylgeranyl diphosphate synthase from a hyperthermophile, Pyrococcus sp. strain OT3.

Pyrococcus sp. strain OT3, a hyperthermophilic archaeon that was isolated by the authors was found to contain tetraether lipid mainly in the membrane lipid, which was quite different from the other hyperthermophiles (Masuchi et al. 1997). Those isoprenoids are synthesized by a family of isoprenyl diphosphate synthases from isopentenyl diphosphate to allylic diphosphates. The gene that encodes one of these families, geranylgeranyl diphosphate synthase (GGPPSase), from this strain was cloned and sequenced. This coding gene has a 960-bp (320aa) sequence. The putative Shine-Dalgarno sequence was six bases upper of start codon, exactly the same as Methanobacterium thermoautotrophicum, a methnogenic thermophile. Comparison of the amino acid sequence of 13 organisms including Eukarya, Bacteria, and Archaea showed that Archaea strains including Pyrococcus sp. strain OT3 consisted of a separate group from the others, but five conservative regions are very homologous.

Journal Article↗

[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↗

Resistance to endotoxic shock in phospholipase A2 receptor-deficient mice.

Mammals possess various types of secretory phospholipase A2, which differ in the primary structure and tissue distribution. The phosholipase A2 receptor (PLA2R) recognizes group IB phospholipase A2 (PLA2-IB) and mediates the PLA2-IB-induced biological responses in non-digestive organs, including eicosanoid production and contraction of airway smooth muscles. In this study, we generated PLA2R-deficient mice to define its biological roles further. These mice are viable, fertile, and without evident histopathological abnormalities. There was no difference in the clearance of circulating PLA2-IB between wild-type and mutant mice. After challenge with bacterial lipopolysaccharide (LPS), PLA2R-deficient mice exhibited longer survival than wild-type mice. The mutant mice were also resistant to lethal effects of exogenous PLA2-IB after sensitization with sublethal dose of LPS. The plasma levels of tumor necrosis factor-alpha and interleukin-1beta elevated after LPS treatment were significantly reduced in mutant mice compared with wild-type mice. These findings suggest a potential role of PLA2R in the progression of endotoxic shock.

Animals↗

The prognostic significance of p53 and bcl-2 expression in lung adenocarcinoma and its correlation with Ki-67 growth fraction.

BACKGROUND: The p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancy. The aims of this study were to determine the relationships between the Ki-67 labeling index (LI) and the expression of p53 and bcl-2 protein in lung adenocarcinoma and to investigate the clinicopathologic features of the tumors and the prognostic significance of p53 and bcl-2. METHODS: Immunohistochemical staining for p53, bcl-2, and Ki-67 was performed on paraffin embedded sections from 114 lung adenocarcinomas from patients who had been treated with complete and potentially curative surgery. To define a cutoff value for p53 immunopositivity, 37 of 114 tumors were examined for p53 gene mutations using cDNA sequencing. The results were compared with clinical outcomes. RESULTS: Expression of p53 protein was defined as nuclear staining in more than 20% of tumor cells, and the concordance rate between p53 expression and gene mutation was 73%. Expression of p53 (39%) was significantly associated with higher Ki-67 LI (P < 0.001) and with several poor prognostic factors, such as poor histologic grade of differentiation (P < 0.05), lymphatic permeation (P < 0.001), and vascular permeation (P < 0.001). Expression of bcl-2 (38%) was significantly associated with favorable T classification (P < 0.001) and smaller tumor size (<2 cm) (P < 0.05) and tended to be associated with lower Ki-67 LI (P = 0.054). In univariate analysis, p53 expression was significantly correlated with poor prognosis (53% vs. 90% at 5 years, P < 0.001) and bcl-2 expression with favorable prognosis (90% vs. 68% at 5 years, P < 0.05). Proliferative activity was highest when only p53 was expressed; by contrast, proliferative activity was lowest when only bcl-2 was expressed. Among four groups of patients, the group that was positive only for p53 had the shortest survival; this difference was statistically significant. Multivariate analysis showed that T classification (P = 0.002), vascular permeation (P = 0.011), and p53 expression (P = 0.03) were independent prognostic factors. CONCLUSIONS: The results of this study indicated an inverse relationship between the proliferative activity of p53 and bcl-2. Expression of p53 was an independent factor associated with poor prognosis, whereas bcl-2 expression was associated with favorable prognosis.

Adenocarcinoma↗

Unaltered secretion of beta-amyloid precursor protein in gelatinase A (matrix metalloproteinase 2)-deficient mice.

The beta-amyloid peptide, which forms extracellular cerebral deposits in Alzheimer's disease, is derived from a large membrane-spanning glycoprotein referred to as the beta-amyloid precursor protein (APP). The APP is normally cleaved within the beta-amyloid region by a putative proteinase (alpha-secretase) to generate large soluble amino-terminal derivatives of APP, and this event prevents the beta-amyloid peptide formation. It has been suggested that the gelatinase A (matrix metalloproteinase 2, a 72-kDa type IV collagenase) may act either as alpha-secretase or as beta-secretase. Mice devoid of gelatinase A generated by gene targeting develop normally, except for a subtle delay in their growth, thus providing a useful system to examine the role of gelatinase A in the cleavage and secretion of APP in vivo. We show here that APP is cleaved within the beta-amyloid region and secreted into the extracellular milieu of brain and cultured fibroblasts without gelatinase A activity. The data suggest that gelatinase A does not play an essential role in the generation and release of soluble derivatives of APP at physiological conditions.

Amyloid beta-Protein Precursor↗

Biologic activity of proteoglycan macrophage colony-stimulating factor.

We compared the biologic activities of 85-kDa macrophage-CSF (85-kDa M-CSF), which is fully active, and a proteoglycan M-CSF (PG-M-CSF). Both originate from the same precursor, but the latter retains the carboxyl-terminal portion, which must be proteolytically removed from the precursor to generate 85-kDa M-CSF and which is uniquely modified by a chondroitin sulfate glycosaminoglycan chain. PG-M-CSF supported the formation of murine macrophage colonies such as 85-kDa M-CSF. Furthermore, PG-M-CSF stimulated the proliferation of murine bone marrow macrophages, an M-CSF-dependent murine cell line, and an M-CSF-responsive human cell line established by transfer of the human M-CSF receptor gene. PG-M-CSF and 85-kDa M-CSF had equivalent specific biologic activities on a molar basis in all bioassays. The activity of PG-M-CSF was not affected by enzymatically removing the glycosaminoglycan chain when assayed by the formation of macrophage colonies and proliferation of the bone marrow macrophages. We analyzed the phosphorylation on tyrosine residue(s) of the M-CSF receptor in response to these M-CSFs that trigger mitogenic responses. PG-M-CSF rapidly (within 10 min) induced receptor phosphorylation in human cells with the same potency as 85-kDa M-CSF. These results indicate that PG-M-CSF is not a latent form or precursor of 85-kDa M-CSF but a fully biologically active cytokine.

Animals↗

Role of nitric oxide and nitric oxide-independent relaxing factor in contraction and relaxation of rabbit blood vessels.

It has been shown that spontaneous release of nitric oxide (NO) from the vascular endothelium attenuates contractile responses of vascular smooth muscles to norepinephrine, and that acetylcholine-induced relaxation is mediated by the evoked release of NO and endothelium-derived hyperpolarizing factor. Since the involvement of these substances (or factors) in mechanical responses is heterogeneous among blood vessels, we have investigated the role of these substances in agonist-induced contraction and relaxation in 6 rabbit blood vessels. Vascular reactivity for the contractile response to norepinephrine was potentiated after removal of endothelium and by 100 microM N(G)-nitro-L-arginine (L-NA) but not by 80 nM-0.4 microM clotrimazole. This potentiation was most marked in the mesenteric artery among the blood vessels tested, suggesting that the basal release of NO reduced the contractile response of the vascular smooth muscle to norepinephrine in this artery. Acetylcholine-induced relaxation was abolished by removal of the endothelium and was attenuated by L-NA (1-100 microM) in all blood vessels. The attenuation by 100 microM L-NA was most obvious in aorta and vein and least in mesenteric resistance artery in which the acetylcholine-induced, L-NA-resistant relaxation was inhibited by 80 nM-0.4 microM clotrimazole. These results suggested that there is a regional difference in the degree of involvement of NO in acetylcholine-induced relaxation. In mesenteric resistance artery, the NO-independent, clotrimazole-sensitive factor, possibly hyperpolarizing factor may also contribute to the response to acetylcholine at high concentrations.

Acetylcholine↗

Determination of ticarcillin epimers in plasma and urine with high-performance liquid chromatography.

A high-performance liquid chromatogaphic method was developed for determining the concentrations of ticarcillin (TIPC) epimers in human plasma and urine. Samples were prepared for HPLC analysis with a solid-phase extraction method and the concentrations of TIPC epimers were determined using reversed-phase HPLC. The mobile phase was a mixture of 0.005 M phosphate buffer (pH 7.0) and methanol (12:1, v/v) with a flow-rate of 1.0 ml/min. TIPC epimers were detected at 254 nm. Baseline separation of the two epimers was observed for both plasma and urine samples with a detection limit of ca. 1 microg/ml with a S/N ratio of 3. No peaks interfering with either of the TIPC epimers were observed on the HPLC chromatograms for blank plasma and urine. The recovery was more than 80% for both plasma and urine samples. C.V. values for intra- and inter-day variabilities were 0.9-2.1 and 1.1-6.4%, respectively, at concentrations ranging between 5 and 200 microg/ml. The present method was used to determine the concentrations of TIPC epimers in plasma and urine following intravenous injection of TIPC to a human volunteer. It was found that both epimers were actively secreted into urine and that the secretion of TIPC was not stereoselective. Plasma protein binding was also measured, which revealed stereoselective binding of TIPC in human plasma.

Adult↗

Enzymic synthesis of 3'-O- and 6'-O-N-acetylglucosaminyl-N-acetyllactosaminide glycosides catalyzed by beta-N-acetyl-D-hexosaminidase from Nocardia orientalis.

beta-N-acetyl-D-hexosaminidase from Nocardia orientalis catalyzed the synthesis of beta-D-GlcNAc-(1 --> 3)-beta-D-Gal-(1 --> 4)-beta-D-GlcNAc-OC6H4NO2-p (1) and beta-D-GlcNAc-(1 --> 6)-beta-D-Gal-(1 --> 4)-beta-D-GlcNAc-OC6H4NO2-p (2) with its isomer beta-D-Gal-(1 --> 4)-[beta-D-GlcNAc-(1 --> 6)]-beta-D-GlcNAc-OC6H4NO2-p (3) through N-acetylglucosaminyl transfer from N-,N'-diacetylchitobiose to p-nitrophenyl beta-N-acetyllactosaminide. The enzyme formed a mixture of trisaccharides 1, 2, and 3 in a ratio of 11:33:56. In the case, when an inclusion complex of p-nitrophenyl beta-N-acetyllactosaminide with alpha-CD was used, compounds 1, 2, and 3 were formed in a molar ratio of 24:63:13. The regioselectivity of glycosidase-catalyzed formation of the trisaccharide glycosides was substantially changed. It resulted not only in a significant increase of the proportion of the desired compounds 1 and 2 but also in the substantial increase of the overall yield of transfer products.

Carbohydrate Sequence↗

Effects of recombinant human bone morphogenetic protein-2 on human bone marrow cells cultured with various biomaterials.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is known to induce orthotopic and ectopic bone formation in vivo. Several in vitro studies using rat or mouse clonal cell lines have shown that rhBMP-2 may be involved in the differentiation of osteoblasts from osteoblast precursor cells or stromal cells in the bone marrow. However, there is little information available about the effects of rhBMP-2 on cultured human bone marrow cells. We investigated the effects of rhBMP-2 cultured on human bone marrow cells and osteoblastic cells on various biomaterials. Human bone cells were divided into fresh bone marrow cells, fibroblast colony-forming units (cfu-F, stromal precursors), and osteoblastic cells. The cells were cultured with or without rhBMP-2 on various biomaterials, including titanium alloy, pure titanium, cobalt alloy, and hydroxyapatite. It was found that rhBMP-2 (500 ng/mL) significantly stimulated alkaline phosphatase production by fresh bone marrow cells and cfu-F. However, when cultured on titanium alloy or pure titanium, only fresh bone marrow cells showed an increase of alkaline phosphatase production after rhBMP-2 stimulation. Production of osteocalcin, a marker of mature osteoblasts, was not stimulated by rhBMP-2 in any combinations tested. These findings suggest that rhBMP-2 may be involved in inducing the differentiation of osteoblast precursor cells into osteoblastic cells rather than stimulating further differentiation of osteoblastic cells into mature osteoblasts. In addition, grafts of fresh human bone marrow cells of cfu-F stimulated by rhBMP-2 may have the potential to promote bone formation at sites of nonunion as well as around titanium joint prostheses.

Adult↗

Activation of c-Jun N-terminal kinase by human granulocyte macrophage-colony stimulating factor in BA/F3 cells.

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces various signaling events in hematopoietic cells. We reported that there are at least two distinct pathways of hGM-CSF signals, one for activation of proliferation and the other one for activation of c-fos promoter through the MAPK cascade. Activation of other members of the MAPK family, c-Jun N-terminal kinase (JNK) and p38 MAPK under various cellular stress have also been reported. We found that hGM-CSF activates JNK in BA/F3 cells expressing the hGM-CSF receptor (hGMR) and that activation depends on a membrane proximal region including box1 and requires a more membrane distal region of hGMR beta subunit (beta c). There are 8 known tyrosine (tyr) residues in the cytoplasmic region of beta c. Mutant beta c lacking all the tyr residues hardly activates JNK, thereby indicating that the tyr residue(s) is essential for the activation of JNK. Mutation analyses of each tyr residue indicated that none of the tyr residues seems essential for the activation of JNK, indicating multiple tyr residues play a similar function to transduce signals for this activation.

Calcium-Calmodulin-Dependent Protein Kinases↗

Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features.

The contiguous 874.423 base pair sequence corresponding to the 50.0-68.8 min region on the genetic map of the Escherichia coli K-12 (W3110) was constructed by the determination of DNA sequences in the 50.0-57.9 min region (360 kb) and two large (100 kb in all) and five short gaps in the 57.9-68.8 min region whose sequences had been registered in the DNA databases. We analyzed its sequence features and found that this region contained at least 894 potential open reading frames (ORFs), of which 346 (38.7%) were previously reported, 158 (17.7%) were homologous to other known genes, 232 (26.0%) were identical or similar to hypothetical genes registered in databases, and the remaining 158 (17.7%) showed no significant similarity to any other genes. A homology search of the ORFs also identified several new gene clusters. Those include two clusters of fimbrial genes, a gene cluster of three genes encoding homologues of the human long chain fatty acid degradation enzyme complex in the mitochondrial membrane, a cluster of at least nine genes involved in the utilization of ethanolamine, a cluster of the secondary set of 11 hyc genes participating in the formate hydrogenlyase reaction and a cluster of five genes coding for the homologues of degradation enzymes for aromatic hydrocarbons in Pseudomonas putida. We also noted a variety of novel genes, including two ORFs, which were homologous to the putative genes encoding xanthine dehydrogenase in the fly and a protein responsible for axonal guidance and outgrowth of the rat, mouse and nematode. An isoleucine tRNA gene, designated ileY, was also newly identified at 60.0 min.

Base Sequence↗

Male to male transmission of supernumerary nipples.

We report on a father and his son with supernumerary nipples. No male-to-male transmission has previously been described with this trait. This observation confirms that this trait is inherited in an autosomal dominant fashion.

Child, Preschool↗

Histone H1 variants as sperm-specific nuclear proteins of Rana catesbeiana, and their role in maintaining a unique condensed state of sperm chromatin.

Amino acid analyses of nuclear basic proteins of an anuran amphibian, Rana catesbeiana, revealed that they are comprised of a full set of core histones and three types of lysine-rich, sperm-specific proteins. On the basis of their amino-acid compositions and partial amino-acid sequences of their trypsin-resistant cores, the sperm-specific proteins could be defined as members of the histone H1 family. Both micrococcal nuclease digestion and electron microscopy indicated that sperm chromatin consists of nucleosomal and fibrillar DNA structures which are irregularly interspersed with each other. When sperm nuclei were incubated with nucleoplasmin, nuclei decondensed to some extent, and the sperm-specific H1s were removed, but not completely. The residual sperm-specific histone H1 variants were also found in reconstituted male pronuclear chromatin, comprising regularly spaced nucleosomes. We conclude that sperm-specific histone H1 variants are essential for chromatin condensation in the sperm nuclei, but that their complete removal is not necessary for the remodeling into somatic chromatin that takes place after fertilization.

Amino Acid Sequence↗