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Biomedical subjects

K Arai

Publications and source records attributed to K Arai.

At least 127 records · Page 7Linked to original sources
PubMed2000

Analysis of signals and functions of the chimeric human granulocyte-macrophage colony-stimulating factor receptor in BA/F3 cells and transgenic mice.

Receptors for GM-CSF, IL-3, and IL-5 are composed of two subunits: alpha, which is specific for each cytokine, and betac, which is shared by all. Although the role of betac in signal transduction has been extensively studied, the role of the alpha subunit has remained to be clarified. To analyze the role of the human (h) GM-CSF receptor alpha subunit, we constructed a chimeric receptor subunit composed of extracellular and transmembrane regions of alpha fused with the cytoplasmic region of betac, designated alpha/beta. In BA/F3 cells, chimeric receptor composed of alpha/beta,beta can transduce signals for mitogen-activated protein kinase cascade activation and proliferation in response to hGM-CSF. Although phosphorylation of Jak1 but not of Jak2 occurred with stimulation of hGM-CSF, the dominant-negative Jak2 but not the dominant-negative Jak1 suppresses c-fos promoter activation. To determine whether the chimeric receptor alpha/beta,beta is functional in vivo, we developed transgenic mice expressing the chimeric receptor alpha/beta,beta. Bone marrow cells from the transgenic mice expressing the alpha/beta,beta receptor form not only GM colonies but also various lineages of colonies in response to GM-CSF. In addition, mast cells were produced when bone marrow cells of the transgenic mouse were cultured with hGM-CSF. Thus, it appears that the cytoplasmic region of the alpha subunit is not required for hGM-CSF promoting activities, even in bone marrow cells.

Animals↗
PubMed2000

Analysis of mechanisms involved in the prevention of gamma irradiation-induced apoptosis by hGM-CSF.

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces proliferation and sustains viability of the mouse interleukin (IL)-3 dependent lymphoid cell line BA/F3 expressing the hGM-CSF receptor. Caspase-3 like enzyme activity and DNA fragmentation were augmented by depletion of this factor from the cell, and exposure to gamma irradiation accelerated kinetics of these events. Anti gamma irradiation-induced apoptosis occurred through various mutant GM-CSF receptors and only the box1 region was essential while the C terminal region, including tyrosine residues which are required for MAPK cascade activation, was dispensable. Consistent with this notion, the addition of PD98059 had no effect on this activity thereby indicating that activation of MAPK is not essential for the activity. As expected, gamma irradiation increased p53 protein and bax mRNA levels and the presence of hGM-CSF dramatically modulated bax/bcl-X(L) ratio. The PI-3K specific inhibitor wortmannin did not affect hGM-CSF dependent anti gamma irradiation induced apoptosis nor bcl-X(L) induction, thus bcl-X(L) but not PI-3K pathway seems to be involved in hGM-CSF dependent anti gamma irradiation-induced apoptosis. It is well documented that the boxl region is essential for GM-CSF dependent activation of JAK2 and JAK2 specific inhibitor AG490 suppressed anti gamma, irradiation-induced apoptosis by hGM-CSF. An artificial JAK2 activating molecule in which extracellular and the transmembrane of beta(c) fused with whole JAK2 can sustain BA/F3 cells survival and proliferation mIL-3 independently, but these cells are susceptible to gamma irradiation. Furthermore GyrB/Jak2, which can activate STAT5 but not the MAPK cascade nor survival of BA/F3 cells, also could not prevent gamma irradiation-induced apoptosis. Although JAK2 is essential for hGM-CSF dependent anti gamma irradiation-induced apoptosis, it appeared that JAK2 does not seem sufficient for the activity.

Animals↗
PubMed2000

Immunohistochemical investigation of migration inhibitory factor-related protein (MRP)-14 expression in hepatocellular carcinoma.

Migration inhibitory factor-related protein (MRP)-8 and -14 belong to the S-100 protein family and are associated with myeloid cell differentiation. MRP is also expressed in some epithelia. However, there are few reports for the investigation on carcinomas. Using the monoclonal antibody 60B8 against MRP-14, we carried out the immunohistochemical evalution of MRP-14 expression in 70 cases of hepatocellular carcinoma (HCC), and examined the relation to tumor differentiation and vascular invasion. Positively stained tumor cells were detected in 32 cases, all of which belonged to grade II (7/30) or grade III (25/25) of the Edmondson-Steiner classification. In particular, the grade III HCC showed a significantly greater positive reaction. Immunopositivity in the non-carcinomatous hepatocytes and bile duct epithelia was not observed. These findings suggested that malignant hepatocytes newly express MRP-14 and that the neo-expression in differentiated HCC is related to the tumor differentiation and shows higher correlation in the poorly differentiated carcinomas. Furthermore, the cholangiocellular carcinoma and metastatic adenocarcinoma as control materials also presented a more marked immunoreactivity for MRP-14 in the poorly differentiated carcinomas, in a similar manner with the findings of the HCC. Accordingly, MRP is considered to be frequently neo-expressed in poorly differentiated carcinomas. MRP-14 expression rate in the 48 HCC cases with vascular invasion was 56%, showing no significant difference compared with non-invasive tumors.

Antigens, Differentiation↗
PubMed2000

Uptake of 99mTc-tetrofosmin, 99mTc-MIBI and 201Tl in malignant thymoma.

99mTc-tetrofosmin, Thallium-201-chloride (201Tl) and 99mTc-MIBI imagings were performed in a patient with malignant thymoma. Tracer uptake in the primary tumor was demonstrated. The tumor-to-background ratios of planar and SPECT imagings were 1.60 and 1.98 for 99mTc-tetrofosmin, 1.12 and 2.09 for 201Tl, and 1.19 and 1.80 for 99mTc-MIBI, respectively. In another patient 99mTc-tetrofosmin and 201Tl imagings were performed. Not only the primary tumor but also the direct invasions and metastatic lesions (bone metastases) were clearly detected. The tumor-to-background ratios of planar and SPECT imagings were 2.31 and 2.78 for 99mTc-tetrofosmin and 2.45 and 3.58 for 201Tl, respectively. In 99mTc-tetrofosmin scintigraphy we acquired delayed images, and the tumor-to-background ratios of planar and SPECT delayed images were 1.20 and 1.86, the retention ratios were -1.11 and -0.92 and the retention indices were -48.1 and -33.1, respectively. Our preliminary results suggest that 99mTc-tetrofosmin is useful in detecting not only the primary tumor but also metastatic lesions from malignant thymoma.

Aged↗
PubMed2000

Reduction of cerebral hyperemia with anti-hypertensive medication after electroconvulsive therapy.

PURPOSE: Several different anti-hypertensive regimens have been introduced for the prevention of systemic hyperdynamic responses after electrically induced seizures. In the present study, the effects of anti-hypertensive medications on cerebral circulation were studied. METHODS: Systemic blood pressure was controlled by several anti-hypertensive medications, nicardipine, prostaglandin EI, alprenolol and nitroglycerin, in 30 patients (150 electroconvulsive therapy trials). Changes in cerebral blood flow velocity were measured by transcranial Doppler sonography of the right middle cerebral artery from the start of anesthesia to 10 min after the electrical shock. RESULTS: Administration of a Ca2+ antagonist, nicardipine, or prostaglandin EI did not alter the augmented cerebral blood flow velocity after the seizure. However, a beta-adrenergic blocking agent, alprenolol (P<0.05) or nitroglycerin (P<0.01) partially inhibited the increase in cerebral blood flow velocity. Maximal blood flow velocity was 133% larger than the pre-anesthesia value in the control group, 109% in the nicardipine group, 113% in the prostaglandin EI group, 72% in the alprenolol group, and 45% in the nitroglycerin group, respectively. The increase in cerebral blood flow velocity after electrically induced seizure was independent of systemic blood pressure. Internal jugular venous saturation (SjO2) was increased, and difference in arterial and venous concentrations of lactate was not altered in all groups. CONCLUSIONS: Cerebral hemodynamics is altered by ECT, even when systemic hemodynamics are stabilized by antihypertensive medication. Although the effects of antihypertensive medicine on cerebral hemodynamics are variable, systemic blood pressure control by these agents does not induce cerebral ischemia after ECT.

Adult↗
PubMed2000

Expression of m2 muscarinic acetylcholine receptor mRNA in primary culture of human prostate stromal cells.

The aim of this study was to investigate the expression of the muscarinic acetylcholine receptor (mAchR) subtypes mRNA in primary culture of human prostate stromal cells using the reverse transcription polymerase chain reaction (RT-PCR), RNA blotting and in situ hybridization (ISH). Using an explant method, we obtained a primary culture of prostate stromal cells from three patients with benign prostatic hypertrophy. Total RNA was extracted using the acid guanidinium method for cDNA synthesis. First-strand cDNA was then used for PCR with primers designed to amplify the fragments of each mAchR subtypes (m1-m5) cDNA sequence. The m2, m3 and m4 subtype expected bands were detected; in particular m2 transcripts was strongly detected in the stromal cell culture. Each of the PCR products were subcloned into the pGEM-T plasmid vector, sequenced and random primer labeled using 32P. Digoxigenin-labeled cRNA probes were synthesized by in vitro transcription. RNA blotting using a m2 muscarinic receptor cDNA probe revealed a 4.5 kb single transcript. However, m3 and m4 probes did not hybridize. Using in situ hybridization (ISH), m2 receptor mRNA signals were detected in several smooth muscle cells. The staining was predominantly localized to the perinuclear cytoplasm. The m3 and m4 probes did not hybridize. These results suggested that m2 receptor subtype plays a role in smooth muscle activity of the human prostate.

Blotting, Northern↗
PubMed2000

Parkinson's disease: affection of brain stem nuclei controlling premotor and motor neurons of the somatomotor system.

Pathological changes which consistently develop in the lower brain stem of patients suffering from Parkinson's disease are described against the background of the internal organization and interconnections of the involved nuclei, i.e., the gigantocellular reticular nucleus, bulbar raphe nuclei, and coeruleus-subcoeruleus area. Immunoreactions against the presynaptic protein alpha-synuclein reveal not only the voluminous forms of Lewy bodies and Lewy neurites but also the otherwise inconspicuous dot- or thread-like types. These lesions develop solely in specific neuronal types. Lipofuscin- or neuromelanin-laden projection cells which at the same time generate a long, unmyelinated or sparsely myelinated axon are particularly susceptible to developing the changes. The bulbar nuclei under consideration receive strong input from supramedullary sources, above all from higher order centers of the limbic system such as the central amygdalar nucleus, periaqueductal gray, and parabrachial nuclei. In turn, they generate descending projections to premotor and motor neurons of the somatomotor system. The disease-related deterioration of both the supramedullary limbic centers and the bulbar brain stem nuclei reduces the limbic influence and markedly impairs the control of premotor and motor neurons. This functional deficit most probably contributes to the overall dysfunction of the motor system typically evolving in the course of Parkinson's disease.

Aged↗
PubMed2000

Evolution of Alzheimer's disease-related cytoskeletal changes in the basal nucleus of Meynert.

This study examines the evolution of Alzheimer's disease (AD)-related pathology in a subcortical predilection site, the basal nucleus of Meynert (bnM), which is a major source of cortical cholinergic innervation. Brains of 51 autopsy cases were studied using silver techniques and immunostaining for tau-associated neurofibrillary pathology and for amyloid beta protein (Abeta) deposits. All cases are classified according to a procedure permitting differentiation of six stages of AD-related neurofibrillary changes in the cerebral cortex. Initial cytoskeletal abnormalities in the bnM are already noted in stage I of cortical neurofibrillary changes. The gradual development of the neurofibrillary pathology in the bnM parallels the progression of the AD-related stages in the cerebral cortex. A variety of morphologically distinguishable cytoskeletal alterations are observed in large nerve cells which predominate in the bnM. Based on these cellular alterations, a sequence of cytoskeletal deterioration is proposed. Initially, the abnormal tau protein is distributed diffusely throughout the cell body and the neuronal processes. Subsequently, it aggregates to form a neurofibrillary tangle, which appears as a spherical somatic inclusion. The cell processes gradually become fragmented. Finally the parent cell dies, leaving behind an extraneuronal "ghost tangle". With regard to the cortical stages of AD-related neurofibrillary changes, the initial forms of cytoskeletal changes in the bnM predominate in the transentorhinal AD stages (I and II), while "ghost tangles" preferentially occur in the neocortical stages (V and VI). The considerable morphological diversity of cytoskeletal alterations is typical of stages III and IV. These results indicate that individual neurons of the bnM enter the sequence of cytoskeletal deterioration at different times.

Aged↗
PubMed2000

Prenatal findings in Brachmann-de Lange syndrome.

We present a case of Brachmann-de Lange syndrome, in which prenatal ultrasonographic evaluation demonstrated increased nuchal translucency, early onset of intrauterine growth retardation, and limb abnormalities in the first, second, and third trimester, respectively.

Adult↗
PubMed2000

Fluoride and magnesium concentrations in human dental calculus obtained from Japanese and Chinese patients.

Calculus deposited on a total of 68 permanent teeth from patients 30-60 years old from Nagoya in Japan and Beijing in China was investigated. An abrasive microsampling method was used to examine the fluoride (F) and magnesium (Mg) distribution, using a fluoride ion-specific electrode and atomic absorption spectrophotometry, respectively. F concentrations decreased from the surface towards the interior of the calculus. Mg concentrations, however, gradually rose towards the innermost surface adjacent to the tooth. In all parts of the depth profiles, the average concentrations of both magnesium and fluoride were higher in the Japanese than in the Chinese calculus. Towards the inner surface of the calculus, F and Mg concentrations were also much higher in the Japanese than in the Chinese group. A greater intake of sea foods and greater use of fluoride dentifrices are possible reasons for the higher F and Mg concentrations in the Japanese individuals.

Adult↗
PubMed2000

Preliminary report of the clinical performance of a new urinary bladder cancer antigen test: comparison to voided urine cytology in the detection of transitional cell carcinoma of the bladder.

We compared the ability of a new urinary bladder cancer antigen (UBC) test with conventional cytology for the detection of transitional cell carcinoma of the bladder using voided urine samples. The UBC was measured and corrected for the creatinine concentration in the urine of 61 patients with transitional cell carcinoma of the bladder (group 1), 23 patients without recurrent bladder tumors during follow-up (group 2), 28 patients with benign prostatic hyperplasia (group 3), nine patients with prostate cancer (group 4), and 90 healthy volunteers free of urological diseases (group 5). The UBC concentrations were 408.8+/-578.5, 18.8+/-26.6, 23.9+/-32.7, 17.5+/-18.6 and 4.6+/-6.7 ngmg(-1) creatinine (mean+/-S. D.) for groups 1-5, respectively. The level for group 1 was significantly higher than for any other group. The sensitivity and specificity, which were optimized using receiver-operating characteristic curves for groups 1 and 2 were 82.0% and 82.6%, respectively, at a threshold value of 39 ngmg(-1) creatinine. The sensitivity and specificity of cytology for these same groups were 60.7% and 86.9%, respectively. The sensitivity of the UBC was significantly higher than that of cytology, not only for total bladder tumors (82.0% vs. 60.7%, P<0.02) but also for grade I transitional cell carcinoma of the bladder (76.5% vs. 11.8%, P<0. 001). While offering a similarly high specificity, the UBC test might have an advantage over cytology in terms of superior sensitivity, particularly for low-grade tumors.

Adult↗
PubMed2000

Functional characterization of the two alternative promoters of human p45 NF-E2 gene.

OBJECTIVE: The transcription factor NF-E2, a heterodimeric protein complex composed of p45 and small Maf family proteins, is considered crucial for the proper differentiation of erythrocytes and megakaryocytes in vivo. We report the results of studies aimed at understanding the regulatory mechanisms controlling p45 gene expression in erythroid cells. MATERIALS AND METHODS: Human p45 mRNAs have two alternative isoforms, aNF-E2 and fNF-E2, and these isoforms are transcribed from the alternative promoters. We investigated lineage-specific expression of both isomers in human erythroid and megakaryocytic cells by reverse transcriptase polymerase chain reaction or Northern blot analysis. For functional characterization of both promoters, plasmids in which reporter genes were placed under the control of a series of truncated or mutated promoter fragments were transfected to human hematopoietic cell lines. RESULTS: When CD34(+) cells isolated from human cord blood were induced to unilineage erythroid or megakaryocytic differentiation in liquid suspension culture, both transcripts, although barely detected at day 0, were induced in both erythroid and megakaryocytic cultures. fNF-E2 mRNA was found to be more abundant in erythroid cells than megakaryocytic cells at day 7 of culture. Although both isomers were expressed in human erythroid-megakaryocytic cell lines, megakaryocytic maturation with loss of erythroid phenotype induced by phorbol 12-myristate 13-acetate (PMA) resulted in exclusive downregulation of fNF-E2, suggesting that fNF-E2 promoter is more erythroid specific. Functional analysis of fNF-E2 promoter showed that the promoter is active only in erythroid-megakaryocytic cells and that the double GATA site in the proximal region is necessary for its efficient activity. CONCLUSION: These results suggest that GATA proteins, which govern the differentiation of erythroid lineage cells, are required for full promoter activity of the p45 gene.

Binding Sites↗
PubMed2000

Stable behavior in a recurrent neural network for a finite state machine.

For the learning of a finite state machine (FSM) by a recurrent neural network (RNN), we think about how to train an RNN so as to stably mimic an FSM even for sequences having a long length. First, we consider the relationship between the stable behavior and the internal representation of states, that is, clusters of the internal units' outputs. As for this relationship, we prove that an RNN can get the stable cluster transitions when a neuron activation parameter is larger than a certain finite value micro0. Secondly, to acquire the stable behavior, we regard the internal representation for the stable behavior as prior knowledge. This produces a new target function of learning with internal representation term. We derive a Bayesian style method to estimate coefficients of the terms in the function, corresponding to hyperparameters. Finally, experiments show that RNNs readily acquire stable behavior by using our proposed method.

Artificial Intelligence↗
PubMed2000

Triterpene alcohol and sterol ferulates from rice bran and their anti-inflammatory effects.

Six novel feruloyl esters of triterpene alcohols and sterols, viz., two trans-ferulates, cycloeucalenol and 24-methylenecholesterol trans-ferulates, and four cis-ferulates, cycloartenol, 24-methyelenecycloartanol, 24-methylcholesterol, and sitosterol cis-ferulates, besides five known trans-ferulates, cycloartenol (CAR), 24-methylenecycloartanol (24-MCA), 24-methylcholesterol, sitosterol, and stigmastanol trans-ferulates, and one known cis-ferulate, stigmastanol cis-ferulate, were isolated from the methanol extract of edible rice bran. These and eight other synthetic trans- and cis-ferulates of triterpene alcohols and sterols, along with the corresponding free alcohols, were evaluated with respect to their anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg per ear) in mice. All of the ferulates showed marked inhibitory activity, and their 50% inhibitory dose (ID(50)) was 0. 1-0.8 mg per ear. On the other hand, whereas two free triterpene alcohols, CAR and 24-MCA, showed strong inhibition (ID(50) 0.2-0.3 mg/ear), eight free sterols examined showed weaker activity (ID(50) 0.7-2.7 mg/ear) than their corresponding ferulates.

Alcohols↗
PubMed2000

Morphologic progression of polypoid colon cancer invading muscularis propria.

To clarify the morphologic progression of polypoid growth in colon cancer invading the musculasris propria, we assessed the morphologic changes in 50 such cancers according to the size and shape of the polyp. The shape of the head of the polyp was defined at the widest slice as semicircular or ulcerated. As the cancer invaded the musculasris propria, the head of the polyp thickened and the structure of the head progressively collapsed, causing its shape to change from semicircular to ulcerated. The proliferating cell nuclear antigen percentage of cells with positively stained nuclei labeling index, determined at the deepest point of invasion, significantly correlated with the morphologic progression of the polyp from semicircular to ulcerated (63.2 +/- 6.7% and 74.9 +/- 7.2%, respectively; P < 0.05). These results indicate that the proliferating cell nuclear antigen labeling index may be a useful marker for the morphologic progression of invasive colonic polyps.

Adult↗
PubMed2000

Epithelioid leiomyosarcoma in a non-immunocompromised infant: additional differential diagnosis of pediatric "round cell tumors".

We report an 18-month-old Japanese girl with purely epithelioid leiomyosarcoma presenting as a huge intraabdominal mass. The patient had been well from birth and had shown no signs of immunodeficiency. She was negative for human immunodeficiency virus. Blood examination revealed elevated serum neuron specific enolase (NSE). Histologically, the tumor was comprised of solid growths of round or polygonal cells with vesicular nuclei and often vacuolated cytoplasm rich in glycogen. The tumor cells were positive for vimentin, NSE, and MIC2, and were negative for desmin and neurofilament. The age, clinical presentation, and histologic findings mostly favored Ewing's sarcoma/primitive neuroectodermal tumor. Silver stain, however, demonstrated well-developed reticulin fibers often outlining individual tumor cells. An expanded panel of immunostains showed that the tumor cells were intensely positive for smooth muscle actin, and ultrastructural study revealed abundant fine cytoplasmic filaments with focal subsarcolemmal densities, various amounts of glycogen, and irregularly arranged, thick basal lamina. The diagnosis of epithelioid leiomyosarcoma was made. Following reduction in tumor size by chemotherapy, the serum NSE level was normalized. From the surgical finding, the primary site was presumed to be the urachus or the urinary bladder dome. Although extremely rare, epithelioid leiomyosarcoma should be added in the list of differential diagnoses of pediatric "round cell tumors."

Abdominal Neoplasms↗
PubMed2000

Heterogenous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation.

We report the characterization of a rare chromosomal translocation, a t(2;11)(q31;p15), which occurred in a patient with de novo acute myeloid leukemia (AML-M4). By 3'-RACE and RT-PCR analyses, two kinds of NUP98-HOXD13 fusion transcript were detected. In addition, we identified a novel fusion transcript, NUP98-FN1, in the same patient. Ectopic expression of the wild-type HOXD13 gene was also observed in the patient, suggesting that HOXD13 contributes to the development of this type of leukemia. The NUP98-HOXD13 fusion transcript was predicted to encode a 552 or 569-amino acid protein containing the Phe-Gly (FG) repeat region of NUP98 and the homeodomain of HOXD13. The NUP98-FN1 fusion transcript was predicted to encode a 482 or 499-amino acid protein consisting of the same N-terminal region of NUP98 and a C-terminal region of 12 amino acids derived from a previously unidentified sequence. We isolated and characterized the chromosomal breakpoints. The breakpoint at 11p15 is mapped within a LINE repetitive element in a 9 kb intron of NUP98, and more than 60% of the sequenced 3 kb region surrounding the breakpoint junction consists of repetitive elements. The other breakpoint at 2q31 is in an intron of FN1, which is located 7 kb upstream of HOXD13, and the repetitive sequence content of the breakpoint junction is low. Local sequence duplications at genomic breakpoints suggest that the t(2;11) translocation is mediated through staggered double-strand DNA breaks. These results throw light on the mechanisms responsible for the generation of t(2;11) translocation and on the processes leading to t(2;11) leukemia.

Acute Disease↗