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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 667 records · Page 37Linked to original sources
PubMed1994

A cloned rat CD38-homologous protein and its expression in pancreatic islets.

Cyclic ADP-ribose recently has been suggested to be an important intracellular signal for insulin secretion. CD38, which was originally isolated from human lymphocytes as a surface marker, is active in the synthesis of cyclic ADP-ribose. We report here the cloning of a rat CD38-homologous protein (CD38H) which is expressed in pancreatic islets. The deduced amino acid sequence shows that rat CD38H is a protein of 303 amino acids (M(r), 34.4 kD) and contains one possible membrane-spanning domain, consistent with a type II transmembrane glycoprotein. The overall identity and similarity of the amino acid sequences between the human CD38 and the rat CD38H are 58% and 76%, respectively. RNA blot analysis showed a strong signal of 3.4 kb in rat brain, duodenum, and heart. CD38H also is shown to be expressed in pancreatic islets by the RT-PCR procedure, but its expression is not significantly different in Wistar and GK rats, a genetic model of non-insulin-dependent diabetes mellitus. The presence of rat CD38H in the pancreatic islets suggests that CD38H may be involved in insulin secretion by synthesizing cADP-ribose.

ADP-ribosyl Cyclase↗
PubMed1994

Results of combined external irradiation and chemotherapy of bleomycin or peplomycin for squamous cell carcinomas of the lower gingiva.

PURPOSE: In Japan, the role of radiotherapy for gingival carcinomas has not been considered as a radical treatment, but only a pre and/or postoperative treatment. This study was aimed to discuss a possibility of radiotherapy for a radical treatment. In this study, radiotherapy was given as an initial treatment for squamous cell carcinomas of the lower gingiva in simultaneous combination with chemotherapy of bleomycin or peplomycin (Tokyo, Japan). METHODS AND MATERIALS: When complete regression of the tumor was obtained, subsequent surgery was postponed with or without a booster of radiotherapy of about 30 Gy until a recurrent lesion was confirmed. RESULTS: Sixty-seven percent of 100 patients with T1 or T2 had complete regression, while only 22 (35.5%) of 62 patients with T3 or T4 had complete regression. The 5-year local control rate by T classification, including the results of secondary treatments (surgery and/or radiotherapy and/or chemotherapy) for recurrent lesions, was 91% for T1, 89% for T2, 76% for T3 and 61% for T4. The 5-year local control rate according to treatment methods was 95% in the group without surgery and 86% in the group with surgery for T1 and T2 patients. The rates were 54% and 71%, respectively for T3 and T4 patients. The cause specific 5-year survival rate by stage was 75% for Stage I, 87% for Stage II, 71% for Stage III, 51% for Stage IV and 70% overall. CONCLUSION: The combination of radiotherapy and chemotherapy could be a conservative radical treatment for T1 and T2 patients with lower gingival carcinoma.

Bleomycin↗
PubMed1994

Novel acyl-CoA:cholesterol acyltransferase inhibitors. Synthesis and biological activity of 3-quinolylurea derivatives.

A series of 3-quinolylurea derivatives (1) was synthesized and evaluated for acyl-CoA:cholesterol acyltransferase (ACAT) inhibitory activity. For in vitro studies, the most potent inhibitory activity was found in derivatives having substituents at the 6,7- or 6,8-positions and an ortho-substituted phenyl group at the 4-position of quinoline ring. The 2,4-difluorophenyl group appeared to be the optimum N'-substituent of the urea moiety. The IC50 values of compounds 52-54 and 59 were in the nanomolar order. Plasma cholesterol-lowering activity of compounds 50, 52, and 54 was observed at less than 1 mg/kg/day in cholesterol-fed rats. Compound 52 was also hypocholesterolemic in hamsters fed a diet without loading cholesterol.

Animals↗
PubMed1994

Induction of programmed cell death in human hematopoietic cell lines by fibronectin via its interaction with very late antigen 5.

Extracellular matrix (ECM) molecules such as fibronectin (FN), collagens, and laminin have important roles in hematopoiesis. However, little is known about the precise mechanisms by which ECM molecules regulate proliferation of human hematopoietic progenitor cells. In this study, we have investigated the effects of ECM molecules, particularly of FN, on the proliferation of a myeloid leukemia cell line, M07E, which proliferates in response to either human granulocyte/macrophage colony-stimulating factor (GM-CSF) or stem cell factor (SCF). The [3H]thymidine incorporation and cell enumeration assays showed that FN strikingly inhibited GM-CSF- or SCF-induced proliferation of M07E cells in a dose-dependent manner, whereas little or no inhibition was induced by collagen types I and IV. The growth suppression of M07E cells was not due to the inhibitory effect of FN on ligand binding or very early events in the signal transduction pathways from the GM-CSF or SCF receptors. DNA content analysis using flow cytometry after staining with propidium iodide revealed that the treatment of M07E cells with FN did not block the entry of the cells into the cell cycle after stimulation with GM-CSF or SCF, whereas the treatment resulted in the appearance of subdiploid peak. Furthermore, FN was found to induce oligonucleosomal DNA fragmentation and chromatin condensation in the cells even in the presence of GM-CSF or SCF, suggesting the involvement of programmed cell death (apoptosis) in the FN-induced growth suppression. The growth suppression or apoptosis induced by FN was rescued by the addition of either anti-FN antibody, anti-very late antigen 5 monoclonal antibody (anti-VLA5 mAb), or GRGDSP peptide, but not by that of anti-VLA4 mAb or GRGESP peptide, suggesting that the FN effects on M07E cells were mediated through VLA5. In addition, the FN-induced apoptosis was detectable in VLA5-positive human hematopoietic cell lines other than M07E cells, but not in any of the VLA5-negative cell lines. These results suggest that FN is capable of inducing apoptosis via its interaction with VLA5, and also raise the possibility that the FN-VLA5 interaction may contribute, at least in part, to negative regulation of hematopoiesis.

Apoptosis↗
PubMed1994

Evidence that impaired intracellular collagen synthesis reduces proliferation in cultured rat hepatocytes.

Contribution of collagen to cell proliferation was studied in cultured hepatocytes. When alpha,alpha'-dipyridyl, an iron chelator which blocks hydroxylation of prolyl and lysyl residues of procollagen and expression of procollagen mRNA, was added to the medium of rat hepatocytes in primary culture, DNA synthesis of the cells was reduced in a dose-related manner without changes in protein synthesis. The reduction of collagen synthesis was parallel with the changes of DNA synthesis. The addition of P-1894B or minoxidil, which inhibits specifically prolyl hydroxylase or lysyl hydroxylase, respectively, also produced similar results. However, the DNA synthesis was not affected by beta-aminopropionitrile fumarate, which inhibits cross linking in extracellular collagen maturation, nor by purified bacterial collagenase. Intracellular processing of collagen synthesis may be required for proliferation in cultured rat hepatocytes.

2,2'-Dipyridyl↗
PubMed1994

Intergenic suppression in a beta subunit mutant with defective assembly in Escherichia coli F1ATPase. Second-site mutation in the alpha subunit.

Substitution of Leu-40 by Pro in the beta subunit (beta L40P) of Escherichia coli F1-ATPase caused a decrease in the amount of the alpha and beta subunits on the membranes. A revertant strain, Re50, carrying no suppression mutations in the uncD gene encoding the beta subunit, was isolated from the beta L40P mutant. The uncA gene from this revertant was amplified by PCR, and cloned into an expression plasmid. The expression plasmid carrying the uncA gene from the revertant was used for genetic suppression assays. The suppression mutation in Re50 was in the alpha subunit, and it recovered the assembly of the alpha and beta subunits into the F1F0 complex and the ATPase activity to 50% that of the wild type. In Re50, Leu-111 was substituted by Gln in the alpha subunit. These results suggest that the regions including Leu-40 in the beta subunit and Leu-111 in the alpha subunit are located close together and interact with each other, either directly or indirectly.

Base Sequence↗
PubMed1994

Changes in the expression of sialyl-Lewisx, a hepatic necroinflammation-associated carbohydrate neoantigen, in human hepatocellular carcinomas.

BACKGROUND: Malignant transformation of cells is associated with the change in their carbohydrate antigens. Sialyl-Lewisx (SLEX) is a necroinflammation-associated carbohydrate antigen (NICA) of liver cells, because it is newly expressed in chronic inflammatory liver diseases. The authors addressed whether this type of carbohydrate antigen shows cancer-associated changes. METHODS: Expression of SLEX and its related structures was studied immunohistochemically using the well characterized monoclonal antibodies in 13 small and 6 advanced hepatocellular carcinomas (HCC). RESULTS: SLEX was negative in 7 small HCC, which were well differentiated histologically. Both negative and positive cells were observed in 6 other small HCC. When positive, SLEX was expressed membranously or cytoplasmically. The membrane positive HCC cells were well differentiated. Cytoplasmic expression was observed in the less differentiated cells. The SLEX-negative cells were associated with any degree of differentiation. In six advanced HCC, the expression of SLEX could also be correlated with their histologic differentiation. HCC expressed sialyl-type 2 chain N-acetyllactosamine (2-NAcLc), but not 2-NAcLc, Lewisx, and Lewisy. CONCLUSIONS: SLEX, a NICA, showed HCC-associated changes that were dependent on the levels of HCC cell differentiation. Suppression and reactivation of alpha 1-3fucosyl-transferase was a possible enzymatic basis for the observed changes.

Adult↗
PubMed1994

Abnormal bone marrow B-cell differentiation in pre-B lymphoma-prone SL/Kh mice.

SL/Kh mice spontaneously develop pre-B lymphomas with surface phenotypes of B220+, BP-1+, Thy-1-, and surface immunoglobulin negative. The immunoglobulin heavy chain of lymphoma is clonally rearranged but the light chain gene remains in germline configuration. Studying prelymphoma stage SL/Kh bone marrow (BM), we found unusual multiclonal expansion of BP-1+ pre-B cells [34.8 +/- 5.8% (mean +/- SD)] by 4 weeks of age, whereas there were far fewer of such cells in most other laboratory strains (8 +/- 5%). The BP-1+ cells did not express surface immunoglobulin, Thy-1.1, or c-kit. Therefore, they seemed to belong to the pre-B II category. Increased numbers of BP-1+ cells were seen in F1 hybrids between SL/Kh and NFS/N; thus it was apparently a dominant heritable property of SL/Kh mice. Emergence of this population was independent of expression of endogenous ecotropic virus, since they were present in BMs of the F1 hybrid to C4W (Fv-4') and were not inhibited by neonatal injection of maternal resistance factor. In the radiation chimeras SL/Kh-->BALB/c, BP-1+ cells appeared abundantly (29.0 +/- 3.8%), whereas in the reciprocal chimeras BALB/c-->SL/Kh, for fewer (5.5 +/- 2.3%) appeared. Therefore, expansion of BP-1+ cells in prelymphomatous BM is a property of SL/Kh stem cells rather than BM microenvironments.

Animals↗
PubMed1994

Molecular analysis of the dhp1+ gene of Schizosaccharomyces pombe: an essential gene that has homology to the DST2 and RAT1 genes of Saccharomyces cerevisiae.

The DST2 gene of Saccharomyces cerevisiae encodes a DNA strand exchange protein, STP beta, which is required for homologous recombination in both mitotic or meiotic cells. We have cloned a DST2-related gene from the fission yeast Schizosaccharomyces pombe and designated it dhp1+. The nucleotide sequence of dhp1+ revealed an open reading frame encoding a protein composed of 991 amino acids. The predicted amino acid sequence was significantly homologous to the S. cerevisiae STP beta, but lacked the carboxy-terminal sequence present in STP beta. Furthermore, dhp1+ shows greater homology to RAT1/HKE1, a gene which is involved in RNA trafficking and processing. Genetic experiments showed that dhp1+ on an S. cerevisiae expression vector could rescue both the defects of the S. cerevisiae DST2 disruptant, slow growth rate and a sporulation defect, and the lethality of the S. cerevisiae rat1ts mutation. This implies the functional similarity of dhp1+ to both DST2 and RAT1. However unlike DST2, dhp1+ is an essential gene for cell growth in S. pombe, suggesting that dhp1+ is not the true homologue of DST2 but rather of RAT1 in S. pombe. The possible roles of dhp1+ in recombination and cell growth in S. pombe are discussed.

Amino Acid Sequence↗
PubMed1994

Reduced sensitivity of dihydroxyacetone on ATP-sensitive K+ channels of pancreatic beta cells in GK rats.

In the GK (Goto-Kakizaki) rat, a genetic model of non-insulin-dependent diabetes mellitus, glucose-induced insulin secretion is selectively impaired. In addition, it has been suggested by previous studies that impaired glucose metabolism in beta cells of the GK rat results in insufficient closure of ATP-sensitive K+ channels (KATP channels) and a consequent decrease in depolarization, leading to a decreased insulin release. We have recently reported that the site of disturbed glucose metabolism is probably located in the early stages of glycolysis or in the glycerol phosphate shuttle. In the present study, in order to identify the impaired metabolic step in diabetic beta cells, we have investigated insulin secretory capacity by stimulation with dihydroxyacetone (DHA), which is known to be directly converted to DHA-phosphate and to preferentially enter the glycerol phosphate shuttle. In addition, using the patch-clamp technique, we also have studied the sensitivity of DHA on the KATP channels of beta cells in GK rats. The insulin secretion in response to 5 mmol/l DHA with 2.8 mmol/l glucose was impaired, and DHA sensitivity of the KATP channels was reduced in beta cells of GK rats. From these results, we suggest that the intracellular site responsible for impaired glucose metabolism in pancreatic beta cells of GK rats is located in the glycerol phosphate shuttle.

Adenosine Triphosphate↗
PubMed1994

A clinical and histopathological study of factors affecting MRI signal intensities of pituitary adenomas.

Our aim was to elucidate the factors which determine the MRI signal intensities of pituitary adenomas. We examined 51 patients with surgically-confirmed pituitary adenomas. Using a spin-echo pulse sequence (SE 500/15), coronal and sagittal images (3 mm slices) were obtained. Signal intensities on T1-weighted images were measured in the parenchyma of the adenoma and in normal grey matter. The relative intensity of the adenoma was assessed by calculating the ratio of its signal intensity to that of the normal grey matter of the same patient. Paraffin-embedded sections were used for haematoxylin and eosin staining. The number of cells in a prescribed area was counted, and the mean of five such counts was taken as the cell density. Immunohistochemically stained sections using antibodies for various pituitary hormones were similarly examined; the ratio of the total number of hormone-positive cells to the overall total number of adenoma cells was calculated. Four independent variables were used in the analysis: the age of the patient, the maximum diameter of the adenoma, the cell density and the proportion of hormone-positive cells in the adenoma and, with the signal intensity ratio as the dependent variable, a multiple regression analysis was performed. This revealed that the the greatest influence upon the signal intensities on T1-weighted images was the proportion of hormone positive cells.

Adenoma↗
PubMed1994

3,4-dihydroxyphenylalanine (dopa) metabolism and retinoic acid induced differentiation in human neuroblastoma.

In mature cells of the sympathetic nervous system and the adrenal gland, the activity of dihydroxyphenylalanine decarboxylase (DDC) is higher than that of tyrosine hydroxylase and 3,4-dihydroxyphenylalanine (dopa) does not accumulate in the cells. On the other hand, it is known that in some neuroblastoma cells there is a relative deficiency of DDC, resulting in accumulation and secretion of dopa. Such a relative deficiency of DDC is a characteristic of neural cells at an early stage of neural crest development, suggesting the neuroblastoma are cells arrested in early neural crest development. If this were the case, it is possible that agents such as retinoic acid (RA) could induce neuroblastoma to differentiate into mature cells with respect to their metabolism of catecholamines. We have measured the effect of RA on the metabolism of dopa and expression of tyrosine hydroxylase and DDC in human neuroblastoma cell lines, CHP-126, CHP-134, IMR-32, NB-69, and LA-N-5. When the cell cultures were treated with RA, they showed wide variations in response as measured by morphological change, growth inhibition, enzyme activities and enzyme expressions. The RA treatment modulated the activities of tyrosine hydroxylase and DDC, but does not increase DDC relative to tyrosine hydroxylase. It is concluded that RA does not induce biochemical differentiation of the neuroblastoma into mature cells even when there are extensive morphological changes and suppression of growth rate.

Cell Differentiation↗
PubMed1994

Early abnormalities of retinal dopamine pathways in rats with hereditary retinal dystrophy.

The dopaminergic pathway that affects rod-driven horizontal cells has been studied in the Royal College of Surgeons (RCS) rat during the period preceding photoreceptor degeneration (postnatal day 17-24). The experiments were performed by intracellular recording from single horizontal cells in vitro. Horizontal cells from the recessive control animals (postnatal day 17-24) were depolarized by dopamine (10 microM) and hyperpolarized by the D1 antagonist SCH 23,390 (10 microM). In contrast, cells from age-matched dystrophic retinas, though depolarized by dopamine, were unaffected by SCH 23390 (10-100 microM), suggesting a significant reduction in the level of endogenous dopamine release. Histologic examination for catecholaminergic neurons revealed no differences in either the cell number or anatomy between the retinas of the control and dystrophic animals. Furthermore, perfusion of the control retinas with melatonin (500 nM-1 microM) yielded response characteristic of the dystrophic type. In the period preceding degeneration, the RCS retina thus displays a discrete abnormality in dopaminergic pathways, such that there is a gross reduction in endogenous dopamine release below that required to activate D1 receptors. Since melatonin levels have been shown to be high in these retinas, we propose that abnormalities in the dopamine-melatonin systems give rise to an electrophysiologic deficit in the postphotoreceptoral retina of the RCS rat.

Animals↗
PubMed1994

The evaluation of hypothalamic somatostatin tone using pyridostigmine and thyrotropin releasing hormone in patients with acromegaly.

To indirectly evaluate the hypothalamic somatostatin (SS) tone in patients with acromegaly, the effects of pyridostigmine (PD), a cholinesterase inhibitor which can inhibit hypothalamic SS secretion, on TRH-induced TSH secretion and the effects of SMS 201-995 on TSH or GH secretion were studied in acromegalic patients (31-69 yr, n = 10), normal young (21-24 yr, n = 7) and normal old male subjects (62-71 yr, n = 7). After pretreatment with PD (60 mg po, -30 min), normal young subjects showed significantly enhanced TSH responses to TRH (500 micrograms i.v., 0 min) compared to single administration of TRH, whereas normal old and acromegalic patients did not show such enhancement. Plasma TSH response to a single administration of TRH in acromegalic patients was significantly lower than that of normal young and old subjects. Although normal young and old subjects showed significantly enhanced GH responses to GHRH (100 micrograms i.v. at 0 min) after the pretreatment with PD (60 mg, -30 min), no such enhancement was observed in acromegalic patients. In contrast, the decrement in plasma TSH after SMS 201-995 administration was similar between normal subjects (5 young 5 old) and 7 acromegalic patients. Further, the maximal plasma GH decrement after administration was significantly greater in acromegalic patients than in the 5 normal young and 5 old subjects p < 0.01). In conclusion, hypothalamic SS tone does not appear to be elevated in acromegalic patients compared to normal young and probably old subjects.

Acromegaly↗
PubMed1994

Neutrophil activation after percutaneous transluminal coronary angioplasty.

We investigated whether percutaneous transluminal coronary angioplasty (PTCA) would induce neutrophil activation in patients with coronary artery disease. Blood samples were taken from the coronary sinus in 14 patients who underwent PTCA and in 9 control subjects who underwent coronary arteriography (CAG). Flow cytometry was used to measure membrane surface expression of beta 2 integrin (CD11b) and the generation of hydrogen peroxide in neutrophils after ex vivo phorbol myristate acetate stimulation by 2,'7'-dichlorofluorescein. Neutrophil elastase was measured by an immunoenzymatic method. Surface expression of CD11b increased significantly, approximately twofold, after PTCA but not after CAG. Mean fluorescence intensity of 2',7'-dichlorofluorescein in stimulated neutrophils decreased significantly after PTCA, suggesting a previous in vivo activation, but not after CAG. Neutrophil elastase increased significantly after PTCA but not after CAG. These data indicate that PTCA induces neutrophil activation and suggest that neutrophils may contribute to the ischemic injury.

Adult↗
PubMed1994

Electrophysiological signs of retinal dopamine deficiency in recently diagnosed Parkinson's disease and a follow up study.

Electrophysiological studies, including electrooculogram (EOG), and simultaneously recorded flash and pattern evoked electroretinograms (FERG and PERG) and visually evoked potentials (FVEP and PVEP) were made in 1988 on 10 newly diagnosed untreated Parkinson's patients at Stage 1 of the Hoehn and Yahr scale. Follow up studies were made on five out of the 10 patients when their disease had progressed to Stage 2 during 1993. The earliest and only sign of abnormality detected in the Stage 1 of Parkinson's patients in 1988 was a delay in the time to reach the peak light rise in the EOG. When the disease had progressed to Stage 2, not only a delay in the time to reach the peak light rise but also a reduction in the amplitude of the peak light rise in the EOG, together with changes in PERG, FERG and PVEPs were demonstrable. These changes observed in PERG, FERG and PVEPs were generally consistent with those reported by previous studies. It is suggested that the reason for the susceptibility of pigment epithelial function to dopamine deficiency in Parkinson's disease may be due to the pigment epithelium being at the extremity of the diffusion pathway from dopamine release sites at the inner plexiform layer.

Adult↗
PubMed1994

KK mouse.

The KK mouse strain shows inherently glucose intolerance and insulin resistance. When KK mice become obese by aging, dietary means or other ways, such a chemical diabetic state is changed to overt diabetic state associated with frank hyperglycemia and glucosuria. Therefore, the KK mouse is a good model for investigating a process of expression of obesity-associated diabetes.

Animals↗