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Biomedical subjects

J Itoh

Publications and source records attributed to J Itoh.

At least 55 records · Page 3Linked to original sources
PubMed1996

Abundant expression of erythroid transcription factor P45 NF-E2 mRNA in human peripheral granurocytes.

Transcription factor NF-E2 is crucial for regulation of erythroid-specific gene expression. p45 subunit of NF-E2 contains a basic-leucine zipper domain and dimerizes with the small Maf family protein to form functional NF-E2 complex. While p45 expression was shown to be restricted to erythroid cells, megakaryocytes and mast cells in hematopoietic lineage, we found in this study that p45 mRNA is abundantly transcribed in the granulocyte fraction of human peripheral blood cells. As neutrophils occupy approximately 92% of the cells in granulocyte fraction of human peripheral blood cells. As neutrophils occupy approximately 92% of the cells in this fraction, the cells expressing p45 is most likely to be neutrophils. p45 mRNA is also expressed in HL-60 promyelocytes, albeit the expression level is much lower than that of the granulocyte fraction. HL-60 cells were found to express mafK mRNA, indicating the presence of genuine NF-E2 complex in the cells. Although p45 mRNA is transcribed from two different promoters, aNF-E2 promoter and fNF-E2 promoter, in erythroid and megakaryocytic lineage cells, p45 mRNA is transcribed only from aNF-E2 promoter. The expression of p45 megakaryocytic lineage cells, p45 mRNA is transcribed only from aNF-E2 promoter. The expression of p45 mRNA in the neutrophils declined rapidly after transfer of the cells to in vitro culture and G-CSF could not sustain the expression from the down-regulation, suggesting the E2 may also participate in the regulation of neutrophil-specific gene expression.

Alternative Splicing↗
PubMed1996

Spontaneous antibody-secreting cells in the stomach of gastric cancer patients.

The gastric mucosa has been regarded as an active site of humoral immunity since the discovery of Helicobacter pylori. The present study was conducted to determine the in vivo activity of gastric B cells in 53 gastric cancer patients. B-cell activity was measured by protein-A plaque assay, in which IgA-, IgM-, and IgG-plaque-forming cells (PFC) were counted. The number of PFC was associated with the stage of cancer, but the response of lymphocytes in a non-tumorous area (NML) and tumor-infiltrating lymphocytes (TIL) differed. PFC in both sites were decreased compared to n0 cancer in n1 lymph node metastasis-positive cancer, while only NML showed raised PFC in n2 + (P < 0.05, vs TIL). Cancer cells penetrating the submucosa caused the PFC of TIL (but not of NML) to decrease. Invasion of the intratumor capillary (V) or lymphatic (Ly) vessels also caused PFC to change, showing differences of Ig class; there was a decrease of PFC in V2 (IgG- and IgM-PFC) and in Ly2 (all Ig-PFC). IgA-PFC in Ly1 differed in TIL (decrease of PFC) and NML (increase). PFC also differed in TIL and NML in cancer cells, as follows: TIL < NML in tubular and poorly differentiated adenocarcinoma and TIL > NML in papillary and signet ring cell adenocarcinoma. Changes in lymph node (LNL) and blood lymphocytes were similar to those in gastric PFC whose IgA value was 10 times as much as that of LNL. The 5-year survival rate was significantly better in patients with lower rather than higher PFC such as 89% vs 68%. Gastric B cells thus appear to be active and to reflect gastric mucosal immunity.

Adult↗
PubMed1996

In situ hybridization analysis of Pit-1 mRNA and hormonal production in human pituitary adenomas.

The pituitary-specific transcriptional factor, Pit-1, is a member of the POU-domain family which has a role in the development and differentiation of three pituitary cell types: somatotrophs, lactotrophs, and thyrotrophs. Recent investigations have suggested the involvement of specific regulation of Pit-1 transcripts in human pituitary adenomas. In this study, we analyzed the expression of Pit-1 gene and Pit-1 product in various human pituitary adenomas using in situ hybridization (ISH) and immunohistochemistry (IHC). Northern hybridization analysis revealed 2.4- and 4.1-kb Pit-1 transcripts in normal pituitary, growth hormone (GH)-, prolactin (PRL)- and thyrotropin (TSH)-secreting adenomas. By ISH analysis, Pit-1 mRNA was detected in 42 (84%) of 50 adenomas. The highest incidence was observed in 15 GH-secreting adenomas and 8 TSH-secreting adenomas, in which Pit-1 mRNA was detected in all cases. Pit-1 mRNA expression was detected in 11 (85%) of 13 PRL-secreting adenomas. In 12 clinically non-functioning adenomas, Pit-1 mRNA was also present in 8 cases, and 5 of these were associated with immunohistochemical expression of Pit-1 product. By combined ISH and IHC, Pit-1 mRNA was often colocalized with GH, PRL or TSH beta immunoreactivities and sometimes colocalized with alpha-subunit of glycoprotein (alpha SU) immunoreactivity. The expression of Pit-1 mRNA in various cell types of human pituitary adenomas in addition to GH, TSH beta and PRL immunoreactivities suggests that Pit-1 may play a role in functional development of pituitary adenomas, including clinically non-functioning adenomas. However, some additional transcriptional factors or enhancers may be required.

Adenoma↗
PubMed1996

Prohormone convertases (PC1/3 and PC2) in rat and human pancreas and islet cell tumors: subcellular immunohistochemical analysis.

Prohormone convertase 1/3 (PC1/3; also termed PC1 or PC3) and PC2 are enzymes that activate prohormones by cleaving the pairs of basic amino acids. This mechanism was initially inferred from the series of several endocrine and neuroendocrine precursor proteins, including proinsulin and proglucagon. To determine the cellular and subcellular distribution of PC1/3 and PC2 in the rat and human pancreas, immunohistochemistry was performed using polyclonal antisera against mouse PC1/3 (ST-28) and mouse PC2 (ST-29). These studies showed light and electron microscopic co-localization of insulin, PC1/3 and PC2, and the coexistence of glucagon and PC2 in the pancreatic islets. This tendency of colocalization was also depicted in one case of human insulinoma and three cases of human glucagonomas, as well as in rat insulinomas. In two cases of human insulinomas, incomplete processing of proinsulin was suggested by the absence of PC2. At the subcellular level in the rat pancreatic islet, the colocalization of PC1/3 and insulin, and that of PC2 and glucagon, were observed in the same secretory granules by immunoelectron microscopy and image analysis. These studies suggest that PC1/3 and PC2 can function with the specificities in the processing of proinsulin and proglucagon into their active forms, respectively, in the normal and neoplastic pancreatic islets.

Adenoma, Islet Cell↗
PubMed1996

Combined non-isotopic in situ hybridisation and indirect immunohistochemical analysis of hormone production in the rat pituitary gland.

An understanding of the intracellular relation between hormonal expression (storage) and gene expression (production) is essential for elucidating the functional status of the individual cells in endocrine tissue such as the pituitary gland. To this end, mRNA expression was visualised by using a combined in situ hybridisation and immunohistochemistry method in routinely processed, formalin fixed, paraffin wax embedded rat pituitaries. mRNA was detected by non-isotopic in situ hybridisation (alkaline phosphatase antialkaline phosphatase method, with nitroblue tetrazolium and 5-bromo-4-chloro-3-indolylphosphate as substrates). Sections were then stained by using the immunoperoxidase method to demonstrate pituitary hormone expression. The specificity of the combined staining method was confirmed by staining adjacent sections separately. The antigenicity of rat growth hormone and prolactin was adequately preserved following hybridisation. In conclusion, this method is specific, easy to use and permits the determination of the functional status of individual cells.

Journal Article↗
PubMed1996

[Isolated angiitis of the central nervous system presenting as subcortical hemorrhage--a case report of benign type].

A 47-year-old woman had an episode of severe headache for a few days. She suddenly experienced right leg weakness and sensory loss. A CT scan revealed subcortical hematoma at the left parietal lobe on admission. Cerebral angiography showed multiple vascular irregularities such as segmentally narrow or sausage-like dialatated areas. Her laboratory studies were entirely normal including antinuclear antibody and coagulation tests. The diagnosis of isolated angiitis of the CNS was made and she responded well to the low dose corticosteroid therapy. Repeated cerebral angiography two months after the onset demonstrated most of the areas of segmental irregularity had improved with a few unchanged areas. Some cerebral angiitis do exist that respond well to corticosteroid therapy, therefore, early diagnosis and treatment are suggested in cases of angiitis.

Cerebral Arterial Diseases↗
PubMed1996

Expression of Pit-1 and estrogen receptor messenger RNA in prolactin-producing pituitary adenomas.

The pituitary-specific transcriptional factor, Pit-1, is a member of the POU-domain family, which has a role in the development and differentiation of three pituitary cell types: somatotrophs, lactotrophs, and thyrotrophs. Recently, specific DNA-dependent interactions have been observed between Pit-1 and nuclear receptors, including: thyroid hormone receptor; retinoic acid receptor; glucocorticoid receptor; and estrogen receptor (ER). The cooperative interaction between Pit-1 and ER required for prolactin enhancer activity in rat pituitaries has been suggested. We analyzed the expression of Pit-1 messenger ribonucleic acid (mRNA) and ER mRNA in 15 human prolactin-producing adenomas using nonradioisotopic in situ hybridization. Their products were also studied by immunohistochemical analysis. Pit-1 mRNA was detected in 12 (80%) of 15 prolactin-producing adenomas. On the other hand, ER mRNA was detected in 14 (94%) of adenomas studied. mRNAs of Pit-1 and ER were detected more frequently than immunohistochemical expression of their products. By combined in situ hybridization and immunohistochemical examination, Pit-1 mRNA and ER mRNA were often colocalized with prolactin immunoreactivities. The colocalizations of Pit-1 mRNA and ER protein were observed in adenoma cells. The high incidence of the expression of ER mRNA in prolactin-producing adenomas may suggest cooperative interactions between Pit-1 and ER in functional differentiation and development of prolactin-producing adenomas.

Adolescent↗
PubMed1995

Clinical application of 18F-FUdR in glioma patients--PET study of nucleic acid metabolism.

Positron emission tomography was used to investigate the metabolism of nucleic acids by 18F-fluoro-2'-deoxyuridine (18F-FUdR) in 22 patients with gliomas. Sixteen cases of high grade glioma clearly demonstrated a region of high activity with a differential absorption rate (DAR) of 0.64 +/- 0.34. Six cases of low grade glioma failed to reveal a positive image of the tumor and the DAR in tumor was 0.21 +/- 0.042 (p < 0.01). This PET-18F-FUdR study succeeded in differentiating high and low grade gliomas from the view point of nucleic acid metabolism.

Adult↗
PubMed1995

Pregnancy outcome among long-term survivors with acute leukemia.

By means of a mail questionnaire, we evaluated the influence of treatment for acute leukemia on offspring of long-term survivors and determined whether the outcome of pregnancy in patients (or spouses) induced relapse of acute leukemia. In 322 replies from the 445 institutions where a questionnaire was sent, there were 1136 adult long-term survivors. We analyzed the 43 adults who had become pregnant or become a father after postremission therapy. The mean age at the leukemia onset was 26.4 and 21.6 years for males and females. Forty-six normal children (26 boys and 20 girls) were born of long-term survivors including 7 pairs of siblings and a pair of twin sisters. There were no malformed babies. There were five abortions. The average duration until delivery was 79 months after diagnosis, and 49 months after the final postremission therapy. Four of 38 parents of live offspring died (3 relapse, 1 other disease), and the other 34 parents of live offspring were in complete remission at the point of this survey. The adverse effect of treatment on the offspring of long-term survivors could not be clarified in this survey. Additional lifetime follow-up of long-term survivors with acute leukemia and their offspring may be necessary.

Acute Disease↗
PubMed1995

Collagenous colitis.

Collagenous colitis is characterized clinically by chronic watery diarrhea and pathologically by colonic mucosal subepithelial collagen deposition. We report a 72-year-old woman who had collagenous colitis associated with chronic watery diarrhea. She received a non-steroidal anti-inflammatory agent (sulindac) because of rheumatoid arthritis. Histological examination of biopsy showed a thick subepithelial collagen layer with lymphocytes, plasma cells, and infiltration of a few eosinocytes in the lamina propria. These findings led to the diagnosis of collagenous colitis. After treatment with salazosulfapyridine, her bowel movement became normalized and mucosal subepithelial collagen deposition disappeared.

Aged↗
PubMed1995

[Exacerbation of seizures by carbamazepine in four children with symptomatic localization related epilepsy].

We treated one hundred and seventy-eight epileptic children with carbamazepine (CBZ) for eight years. Among them, four children with symptomatic localization-related epilepsy, aged 11 months to 12 years, developed exacerbation of seizures. Their epilepsies were associated with hypoxic ischemic encephalopathy, head injury and ectopic gray matter. Despite the serum levels of CBZ (7.0 approximately 9.5 micrograms/ml) being within the therapeutic range, all of them had more frequent and severe partial seizures than before taking CBZ and one developed new atonic seizures. Diffuse irregular spike-wave complexes appeared on EEG in two children. Following discontinuation of CBZ in addition to replacement with phenytoin, their seizures became well-controlled and EEG findings improved except for residual focal spikes. Although CBZ is a widely used and effective antiepileptic drug for partial seizures, it should be kept in mind that CBZ may exacerbate seizures in children with symptomatic localization-related epilepsy.

Carbamazepine↗
PubMed1995

The role of proinflammatory and immunoregulatory cytokines in the pathogenesis of ulcerative colitis.

We investigated the production of proinflammatory cytokines (IL-1 beta, IL-6, IL-8, and TNF-alpha) and immunoregulatory cytokines (IL-2, IFN-gamma, and IL-10) in the colonic mucosa of patients with active ulcerative colitis (UC), inactive UC, and non-inflammatory bowel disease (IBD) colitis by organ culture. The production of proinflammatory cytokines was significantly increased in all the studied groups compared with controls. In active UC, levels of these cytokines, except for IL-1 beta, were markedly increased compared with non-IBD colitis, and the levels were positively correlated with the degree of inflammation. Patients with non-refractory active UC receiving steroids showed levels of IL-1 beta and TNF-beta production similar to those in controls. IL-10 production was also significantly increased in all the studied groups, the value of being the highest in active UC. In contrast, IL-2- and IFN-gamma production was significantly decreased in both active and inactive UC compared with controls, and the values in active UC were inversely correlated with the degree of inflammation. In non-IBD colitis, decreased IL-2 production was observed, but IFN-gamma production did not differ from that in controls. In an experimental study, each of the proinflammatory cytokines was injected into the colonic mucosa of rats. All of these proinflammatory cytokines, except for IL-1 beta induced colonic mucosal damage that showed some histologic features similar to those of UC. These results suggest that the increased production of proinflammatory cytokines, particularly of IL-6 and IL-8, and the decreased production of IL-2- and IFN-gamma, probably downregulated by the enhanced production of IL-10, play an important role in the pathogenesis of UC.

Animals↗
PubMed1995

Immunohistochemical characterization of "hyperplasia-adenoma sequence" in the pituitaries of transgenic mice expressing a human growth hormone-releasing factor gene.

The morphology of hyperplastic pituitaries in seven human growth hormone-releasing factor (hGRF) transgenic mice were compared to those of two normal control mice. Under continuous stimulation by hGRF, both the total volume of the pituitary and the size of individual cells increased, and a nodular lesion, designated a "hypertrophic nodule", was identified. Immunohistochemically, the hyperplastic pituitaries consisted of various numbers of cells immunoreactive for rGH, rPRL, hACTH, rLH beta, hFSH beta, and r alpha SU, whereas the "hypertrophic nodule" was composed of rGH, rPRL, and rTSH beta positive cells, similar to the adenoma. The presence of the "hypertrophic nodule", which was intermediate in appearance between the controls and the adenomas, suggests a close relation between continuous hGRF stimulation and the development of a hyperplasia-adenoma sequence in the pituitary.

Adenoma↗
PubMed1994

Behavioral evidence for a modulating role of sigma ligands in memory processes. I. Attenuation of dizocilpine (MK-801)-induced amnesia.

The potentiating effect of low doses of sigma ligands on the N-methyl-D-aspartate (NMDA)-induced excitation of pyramidal CA3 dorsal hippocampal neurons has recently been reported. In the present study, we investigated behavioral effects relevant to these findings in the experimental amnesia induced by the non-competitive NMDA antagonist, dizocilpine (MK-801), in mice. At doses below 1 mg/kg s.c., the sigma ligands, 1,3-di-(2-tolyl)guanidine (DTG), (+)-SKF 10,047, and (+)-pentazocine, but not their (-)-isomers, significantly decreased MK-801 (100 microgram/kg s.c.)-induced impairment of spontaneous alternation performances in 8-min sessions of a Y-maze exploration, an index of spatial working memory, without affecting the concomitant hyperlocomotion. The effect of DTG (100 micrograms/kg s.c.) was completely antagonized by the simultaneous administration of BMY 14802 (10 mg/kg i.p.) and NE-100 (1 mg/kg i.p.), two putative sigma antagonists, which had no effect by themselves. In long-term memory tests (step-down and step-through types of passive avoidance, elevated plus-maze), DTG exhibited a significant attenuation of MK-801-induced amnesia, at doses of 10 and 100 micrograms/kg s.c. In all tests of short- and long-term memory, the effects exhibited by the sigma ligands tested had a bell-shaped curve; no effect was seen at 1 mg/kg. DTG did not affect the impairment of alternation induced by CPP (5 mg/kg i.p.): the modulation may selectively target the blockade of NMDA receptor-associated ion channels. Moreover, DTG (1-1000 micrograms/kg) did not affect the impairment induced by scopolamine (1 mg/kg i.p.) or diazepam (4 mg/kg i.p.), but significantly prevented the impairment induced by mecamylamine (10 mg/kg i.p.). These results suggest that the potentiating effect of sigma ligands on NMDA receptor-mediated glutamatergic neurotransmission, already demonstrated electrophysiologically, may have some relevance to learning and memory processes in the hippocampus. A similar modulation may also affect cholinergic nicotinic systems.

Amnesia↗
PubMed1994

Low dose of 1,3-di(2-tolyl)guanidine (DTG) attenuates MK-801-induced spatial working memory impairment in mice.

MK-801 (30-100 micrograms/kg, SC) impaired spontaneous alternation behavior of mice, a behavior related to the spatial working memory. 1,3-Di-(2-tolyl)guanidine (DTG), (+)-pentazocine and (+)-SKF 10,047 (100 micrograms/kg, SC), putative sigma agonists, administered 10 min before MK-801, partially but significantly reversed the impairment, without affecting the concomitant hyperlocomotion. The antagonizing effects by DTG were prevented by BMY-14802 (5 mg/kg, IP), a purported sigma antagonist. These findings suggest that, at low doses, sigma ligands may modulate the N-methyl-D-aspartate dependent memory processes.

Animals↗
PubMed1994

Bio-histochemical aspects of integrins (alpha 2 beta 1, alpha 6 beta 1) in invasive mammary carcinomas: an immunohistochemical study.

Immunohistochemical expression of integrins was examined in 39 human invasive mammary carcinomas, of which 34.2% and 43.6% expressed integrins alpha 2 beta 1 and alpha 6 beta 1, respectively. Immuno-electron microscopy clearly demonstrated that the integrins were in the cell membrane of the carcinoma cells. Similar expression of integrin alpha 2 beta 1 or alpha 6 beta 1 in both the intraductal component and invasive portion of the same tumor was seen in 76.9% and 85.7% of cases, respectively. This suggested that invasive carcinoma cells retained their integrin expression after invasion through the basement membrane. Reciprocal expression of integrins alpha 2 beta 1 and alpha 6 beta 1 was seen in 20 cases. Expression of alpha 2 beta 1 was seen significantly less frequently in scirrhous carcinoma than in the more differentiated papillotubular or solid tubular carcinoma (Chi-squared test, P < 0.05). Intraductal components of carcinoma were present more frequently in cases expressing integrin alpha 2 beta 1 than in those that were negative. This suggests the potential usefulness of integrins as clinical parameters in the surgical treatment of mammary carcinoma, since recent trials of conservative treatment for mammary carcinoma have focused on the intraductal spread of the tumor cells.

Antigens, CD↗
PubMed1994

Nephritogenic antibodies in MRL/lpr lupus mice: molecular characteristics in pathological and genetic aspects.

MRL/lpr mice spontaneously develop a lethal glomerulonephritis (GN). We found that IgG3 production in this strain of mice has a critical role on the development of GN; 1) IgG3 levels were high in kidney-extracted IgG and in circulating IgG immune complexes (IC), 2) serum IgG3 was selectively reduced by cyclosporin A treatment, associated with amelioration of GN, and 3) the mRNA levels of IgG3 correlated well with the severity of GN among the MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice with the rearranged genetic profile. Based on these results, we have successfully established five hybridoma clones which produce nephritogenic IgG3 antibodies from an unmanipulated MRL/lpr mouse. When they were injected to normal mice, four of the five clones generated cell-proliferative GN associated with the marked cellular infiltrates, while the remaining clone induced wire loop-like lesions. This result suggests that particular antibodies generated in MRL/lpr mice have a different pathogenic potency. The V-region sequence study of these nephritogenic antibodies revealed that the two types of the glomerular lesions were mediated by a different B cell precursor. In conclusion, GN in MRL/lpr lupus mice is thought to be generated by the expansion of clonally different B cells producing nephritogenic antibodies with a different pathogenic potency.

Amino Acid Sequence↗