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Biomedical subjects

N Harada

Publications and source records attributed to N Harada.

At least 343 records · Page 19Linked to original sources
PubMed1995

Interleukin-3, granulocyte-macrophage colony-stimulating factor, and interleukin-5 transduce signals through two forms of STAT5.

Recently, JAK2 kinase was found to be one of the tyrosine kinases activated by interleukin-3 (IL-3) in target cells. JAK2 belongs to a family of kinases that act upstream of transcription factors called STATs. STATs exist in the cytoplasm as latent, transcriptionally inactive forms until, in response to extracellular signals, they become phosphorylated on tyrosine residues, translocate to the nucleus, and bind to specific DNA elements. Because IL-3 activates JAK2, we searched for the STAT(s) that might transduce IL-3 signals. Several lines of evidence suggest that IL-3 uses the murine homologue of STAT5, a factor originally purified from sheep. Unexpectedly, during isolation of the murine homologue, we found two highly related molecules that we have designated STAT5A and STAT5B.

Animals↗
PubMed1995

DNA-based prenatal carrier detection for group A xeroderma pigmentosum in a chorionic villus sample.

DNA-based prenatal carrier detection of group A xeroderma pigmentosum (XP-A) is reported. Chorionic villus sampling was done at the tenth gestational week in a pregnant woman whose first child suffers from XP-A. Genomic DNAs from the villi, proband, and parents were PCR (polymerase chain reaction)-amplified using three sets of primers, because the PCR and a subsequent enzyme digestion with HphI, AlwNI, or MseI may detect the three most frequent mutations of the XP-A complementing gene (XPAC) in Japanese XP-A patients. The results showed that the proband is a homozygote and that the parents and fetus are heterozygotes for a base substitution at the 3' acceptor site of intron 3 of XPAC, indicating that the fetus is a healthy carrier of XP-A. This is the first case of prenatal carrier detection of the disorder.

Base Sequence↗
PubMed1995

A synthetic peptide corresponding to a critical intracellular signaling region of the human IL-4 receptor inhibits IL-4-induced proliferation.

We have previously identified a critical region for growth signal transduction in the cytoplasmic domain of the human IL-4 receptor (hIL-4R). Since the entire cytoplasmic domain of this receptor lacks known catalytic activities such as the tyrosine kinase domain, it is likely that the IL-4R associates with other signal-transducing molecules through this critical cytoplasmic region. We test here whether a synthetic peptide corresponding to this critical cytoplasmic region, designated SP-1, interferes with IL-4-induced proliferation by competing with the IL-4R for binding to intracellular signal-transducing molecules. Our data indicated that 100 micrograms/ml SP-1 peptide completely inhibits human IL-4 (hIL-4)-induced proliferation of Ba/F3 transfectants expressing the full-length hIL-4R (hIL-4R-Ba/F3 transfectants). In contrast, a wide concentration range of an unrelated synthetic peptide, designated SP-2, did not affect hIL-4-induced proliferation of hIL-4R-Ba/F3 transfectants. This difference between SP-1 and SP-2 peptides was not due to their differential uptake by cell, since approximately 100 times more SP-2 peptide could be found in cytoplasmic extracts than SP-1 peptide in experiments using radiolabeled peptides. The specificity of SP-1-mediated inhibition of IL-4-induced proliferation was supported by the fact that the SP-1 peptide had no effect on IL-3-induced proliferation of the same hIL-4-Ba/F3 transfectants. In addition, the SP-1 peptide did not affect either IL-2-induced proliferation of Ba/F3 transfectants expressing the human IL-2 receptor beta chain (hIL-2R beta) or hIL-4-induced proliferation of Ba/F3 transfectants expressing a chimeric receptor consisting of the hIL-4R extracellular domain and the hIL-2R beta cytoplasmic domain. SP-1 was unable to inhibit IL-4-induced proliferation of other IL-4-responsive cell lines such as human erythroleukemic cell line TF-1 and mouse T cell lines HT2 and CTLL-2. In addition, SP-1 caused only a 50% inhibition of Ba/F3 cell proliferation induced by mouse IL-4. The failure of SP-1 to inhibit IL-4-induced proliferation in these various cell lines while producing excellent inhibition of hIL-4-induced proliferation of hIL-4R-Ba/F3 transfectants appeared to be related to the number of IL-4Rs expressed on each cell type.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1995

Aromatase-immunoreactive cells are present in mouse brain areas that are known to express high levels of aromatase activity.

The transformation of testosterone into estradiol in the brain plays a key role in several behavioral and physiological processes, but it has been so far impossible to localize precisely the cells of the mammalian brain containing the relevant enzyme, viz., aromatase. We have recently established an immunohistochemical technique that allows the visualization of aromatase-immunoreactive cells in the quail brain. In this species, a marked increase in the optical density of aromatase-immunoreactive cells is observed in subjects that have been treated with the aromatase inhibitor, R76713 or racemic Vorozole. This increased immunoreactivity, associated with a total blockade of aromatase activity, has been used as a tool in the present study in which the distribution of aromatase-immunoreactive material has been reassessed in the brain of mice pretreated with R76713. As expected, the aromatase inhibitor increases the density of the immunoreactive signal in mice. Strongly immunoreactive cells are found in the lateral septal region, the bed nucleus of the stria terminalis, the central amygdala, and the dorso-lateral hypothalamus. A less dense signal is also present in the medial preoptic area, the nucleus accumbens, several hypothalamic nuclei (e.g., paraventricular and ventromedial nuclei), all divisions of the amygdala, and several regions of the cortex, especially the cortex piriformis. These data demonstrate that, contrary to previous claims, aromatase-immunoreactive cells are present in all brain regions that have been shown previously to contain high aromatase activity.

Animals↗
PubMed1995

Involvement of the central nervous system in vibration syndrome.

In order to clarify the involvement of the central nervous system (CNS) in vibration syndrome (VS), patients with VS and age-matched controls were given a questionnaire and neurophysiological tests on auditory brainstem response (ABR), event-related potential (P300), short-latency somatosensory evoked potentials (SLSEP), and blink reflex (BR). Twenty-eight patients with a mean age of 56.3 (SD = 3.01, range 48-65) years from western Japan were examined. They had been on sick leave for an average of 6.13 (SD = 3.2, range 1-13) years at the time of the testing. Almost all were experiencing Raynaud's phenomenon in the winter of 1990-1991. They were not suffering from diseases or injuries which might have affected the CNS function. These patients were divided into two subgroups, one with more symptoms related to the CNS, especially memory and judgment (n = 13, group A), and the other with fewer symptoms (n = 15, group B). Normal controls with an average age of 55.8 (SD = 4.8, 48-65) years were people from the same area who met similar criteria. The ABR parameters of the patients were slightly, but not significantly, delayed compared with those of the controls. The SLSEP and BR parameters of the patients were not delayed. The latencies of P300 in group A were significantly delayed compared with those in the controls. The findings suggest that VS involves the cognitive and attention functions of the cerebral higher function, but not the conduction function in the auditory and somatosensory ascending tract and facial nerve reflex tract in the brainstem.

Central Nervous System↗
PubMed1995

Diquat increases cysteine proteinase inhibitors greatly in rat plasma and tissues.

Biochemical and gross pathological effects of diquat were studied with special attention to cysteine proteinase inhibitor level which was often increased in acute and chronic disorder. Diquat was fed continuously to rats at the dose of 1000 ppm in the diet. After 10 days, anorexia and severe diarrhea were observed but epistaxis and hypokinesia were not apparent. The rats were killed after feeding the diet for 13.5 days and plasma components such as acute phase reactant proteins and some vitamins which act as antioxidants were examined. The results showed that alpha-cysteine proteinase inhibitor (alpha-CPI) increased to 9-fold and vitamin C radical increased to 1.6-fold, whereas alpha 1 proteinase inhibitor (alpha 1-PI) decreased to 0.9-fold and vitamins C and E were the same as the control. Among three components of alpha-CPI, the T kininogen level in intoxicated rat plasma was about 20-fold, whereas the high molecular weight kininogen level was about 2-fold of the control. Diquat also enhanced the cysteine proteinase inhibitor (CPI) level to 20-fold in kidney and to 7- to 10-fold in the other organs. The large increment of T kininogen in these organs was also confirmed immunologically. The kidney showed a granular degeneration and its weight increased to 1.2-fold of control. The other organs showed neither gross pathological alteration nor weight change, compared with the control. The diquat distribution was highest in spleen and next highest in kidney among several organs. These results were compared with those caused by paraquat.

Animals↗
PubMed1995

Two endothelin receptors (ETA and ETB) expressed on circular smooth muscle cells of guinea pig cecum.

BACKGROUND/AIMS: The functional receptors for endothelin (ET) in colonic smooth muscle are still unknown. This study investigated the expression of ET receptors in isolated circular smooth muscle cells of guinea pig cecum. METHODS: Inhibition of 125I-ET-1 binding was examined using unlabeled ET-1, ET-2, ET-3, sarafotoxin 6c (S6c), and ETA antagonists. Expression of the ET-receptor message was investigated using reverse-transcription polymerase chain reaction. The contractile potency of the ET family and the inhibitory effect of ETA antagonists on ET-1-induced contraction were also investigated. RESULTS: Unlabeled ET-1, ET-2, and ET-3 inhibited the specific binding of 125I-ET-1 in a concentration-dependent manner, but the inhibitory effect of ET-3 was smaller than those of ET-1 and ET-2. At a 10(-6) mol/L concentration of S6c, the specific binding of 125I-ET-1 was 24.7%. S6c had clearly reached maximal inhibition. Abundant polymerase chain reaction products for both the ETA and the ETB message were observed. ET-1 and ET-2 showed similar contractile potency, but ET-3-induced and S6c-induced contractions were significantly less potent than the ET-1-induced contraction. A significant response to S6c was obtained at a concentration as low as 10(-10) mol/L. The ETA antagonists BQ-123 and FR 139317 significantly inhibited ET-1-induced contraction. CONCLUSIONS: The results show a direct contractile effect of ETs on circular smooth muscle of guinea pig cecum and the presence of both ETA- and ETB-receptor subtypes.

Animals↗
PubMed1995

Interaction between atrial natriuretic peptide and vasoactive intestinal peptide in guinea pig cecal smooth muscle.

BACKGROUNDS & AIMS: The role of atrial natriuretic peptide (ANP) in gastrointestinal motility is still unclear. The aim of this study was to investigate the relationship between ANP and vasoactive intestinal peptide (VIP) in guinea pig cecal circular smooth muscle cells. METHODS: The inhibition of 125I-ANP binding or 125I-VIP binding to cecal smooth muscle cells was assessed using unlabeled peptides (i.e., ANP, ANP fragments, VIP, secretin, and peptide histidine isoleucine); the effect of ANP, ANP fragments, and VIP on muscle contraction stimulated by 1 mumol/L carbachol was assessed; and the inhibitory effects of ANP 1-11 on VIP-induced relaxation, ANP 1-11 and VIP 10-28 (a VIP antagonist) on ANP-induced relaxation, and nitric oxide production inhibitors on ANP-induced relaxation were assessed. RESULTS: The specific binding of 125I-ANP was inhibited completely by unlabeled ANP and VIP in a dose-dependent manner but only slightly inhibited by secretin and peptide histidine isoleucine. ANP 1-11 and C-atrial natriuretic factor inhibited the binding of 125I-ANP with a lower affinity than ANP. ANP only partly inhibited 125I-VIP binding. ANP and VIP inhibited 1 mumol/L carbachol-induced contraction in a dose-dependent manner. ANP 1-11 significantly inhibited VIP-induced relaxation. ANP 1-11, VIP 10-28, and NO production inhibitors completely inhibited ANP-induced relaxation. CONCLUSIONS: The results of the study showed that ANP 1-11 antagonized ANP-induced relaxation and that ANP stimulated NO production and subsequently induced relaxation via a receptor to which VIP binds.

Animals↗
PubMed1995

Shear and tensile bond testing for resin cement evaluation.

OBJECTIVES: The aim of this study was to compare the tensile and shear bond strengths of one experimental and four commercially available resin cements following the ISO document TR 110405 for bond measurement. METHODS: Tensile and shear bond tests were performed using bovine enamel and dentin as the tooth substrate with each of the resin cements. Resin composite rods were cemented to the prepared tooth surfaces. The bond strengths were obtained 24 h after cementation, and mode of failure was classified after fracture of the bonds, both visually and by SEM observation. RESULTS: Significant differences existed between the two bond test methods for all materials with enamel and three of the five cements when bonded to dentin. The shear test results were always the higher of the two test methods. Mode of fracture varied little for the visual classification, but the morphology from SEM observations showed considerable differences. SIGNIFICANCE: Although there are deficiencies in the current test methods these may be outweighed by substrate variables. A test model should be designed to determine which stresses, tensile or shear, are the greatest for different types of restorations. With this information, the type of test selected could provide appropriate information before clinical trials are commenced.

Aminosalicylic Acids↗
PubMed1995

The critical region in the cytoplasmic domain of human IL-4 receptor for induction of IgE synthesis.

To examine the region critical for differentiation in the human IL-4 receptor (hIL-4R), we transfected the Abelson murine leukemia virus (A-MuLV)-transformed murine pre-B cell line A20 with plasmid DNA encoding the hIL-4R. Transfectants expressed high affinity hIL-4Rs on the cell surface. Treatment with LPS and hIL-4 induced germline C epsilon transcripts in hIL-4R expressing A20 cells. Several hIL-4R mutant plasmids were then transfected into A20 cells and the transfectants were examined for hIL-4R expression and the ability to induce germline C epsilon transcripts upon stimulation with LPS and hIL-4. Although all A20 transfectants tested expressed the high-affinity hIL-4R, A20 transfectants expressing the mutant hIL-4R, which contains only 8 amino acids in the cytoplasmic domain, did not respond to LPS and hIL-4 with germline C epsilon transcripts. In addition, A20 transfectants expressing an internally deleted hIL-4R, in which the deleted region has been identified as the critical region for growth signal transduction in the previous study, failed to induce germline C epsilon transcripts with LPS and hIL-4. These results indicate that the critical region for the differentiation signal in the hIL-4R is identical to that for the growth signal, suggesting that IL-4 may share, at least partly, a common signal pathway for both growth and differentiation.

Animals↗
PubMed1995

Critical re-examination of the distribution of aromatase-immunoreactive cells in the quail forebrain using antibodies raised against human placental aromatase and against the recombinant quail, mouse or human enzyme.

Mouse and quail aromatase cDNAs were isolated from libraries of mouse ovary and quail brain by using a human aromatase cDNA fragment (hA-24) as a probe. These three cDNAs were inserted into plasmid vectors and expressed in Escherichia coli. Antisera against these purified recombinant proteins were raised in rabbit and purified by ammonium sulfate fractionation and affinity chromatography. The three antibodies directed against recombinant human, mouse and quail proteins were used to visualize aromatase-immunoreactive cells in the quail brain. They were compared with the antibody raised against human placental aromatase used in previous experiments and with another antibody recently developed by similar methods. The signal obtained with all antibodies was completely abolished by preadsorption with the homologous recombinant antigens and the signal produced by the two antibodies raised against placental aromatase was similarly abolished by a preadsorption with recombinant quail aromatase. The antibodies raised against recombinant proteins identified the major groups of aromatase cells previously described in the quail brain. The antibodies directed against the mouse and quail antigen identified more positive cells and stained them more densely than the antibodies raised against human recombinant antigen or purified placental aromatase. The new cell groups identified by the antibody raised against quail recombinant aromatase were located in an area ventral to the fasciculus prosencephali lateralis, the nucleus accumbens, the paleostriatum ventrale, the nucleus taeniae, the area around the nucleus ovoidalis, the caudal tuber and the mesencephalic central gray. A critical re-examination of the distribution and nomenclature of the aromatase-positive cells is proposed based on these new findings.

Animals↗
PubMed1995

Endoscopic ultrasound-guided pancreatography: a case report.

Endoscopic ultrasound-guided pancreatography was performed on a 48-year-old man with a diagnosis of pancreatic stone. A pylorus-preserving pancreaticoduodenectomy had been performed previously on this patient, approximately two years earlier, following the diagnosis of a tumor-forming pancreatitis. Endoscopic retrograde pancreatography and conventional ultrasound-guided percutaneous pancreatography had failed to yield a diagnosis. However, endoscopic ultrasound-guided pancreatography was performed successfully, delineating the pancreatic duct and a filling defect caused by intraductal calculi. Endoscopic ultrasound-guided pancreatography will be a potential alternative in cases when endoscopic retrograde pancreatography has failed or proved non-diagnostic.

Calculi↗
PubMed1995

Acute-phase reactant proteins and antioxidants in rats intoxicated chronically with paraquat.

Paraquat dichloride at 250 ppm in the diet was fed continuously to rats. Though no apparent effect of paraquat was observed until 10 d, some rats then began to show several symptoms such as diarrhea, anorexia, epistaxis, and hypokinesia, and in some cases rats died after this period. The biochemical examination of plasma components revealed appreciable changes in the concentrations of an acute-phase reactant protein and some vitamins that act as antioxidants. alpha-Cysteine proteinase inhibitor increased by 5-fold, and vitamin C and its radical increased by 1.5- and 1.7-fold, respectively, whereas alpha 1 proteinase inhibitor decreased slightly. Paraquat enhanced the cysteine proteinase inhibitor levels in lung, liver, and kidney by 6.2-, 6.0-, and 4.5-fold of control, respectively. Among three components of alpha-cysteine proteinase inhibitor, the T kininogen level of treated rat plasma was about eight-fold higher than control, whereas the high-molecular-weight kininogen level was unchanged. The large increment of T kininogen was also seen in lungs of the treated rats.

Acute-Phase Proteins↗
PubMed1995

Screening for balance and mobility impairment in elderly individuals living in residential care facilities.

BACKGROUND AND PURPOSE: The rapid growth of the elderly population has resulted in a corresponding rise in the number of elderly individuals who experience disability during their lifetimes. The purpose of this study was to test the usefulness of four established clinical measures of balance, gait, and subjective perceptions of fear of falling as screening methods for referring community-dwelling elderly individuals living in residential care facilities for detailed physical therapy evaluation and possible intervention. SUBJECTS: The subjects were a convenience sample of 53 elderly individuals living in two residential care facilities for the elderly. METHODS: Subjects were tested on each of four clinical measures of balance and mobility. Their performance on these measures was compared with a physical therapist's brief evaluation of disability and appropriateness for more detailed evaluation. The usefulness of these tools as screening methods was determined by calculating sensitivity and specificity levels using the physical therapist's evaluation as a standard. RESULTS: The sensitivity and specificity levels of the four clinical measures in their application as screening tests for referral to physical therapy were as follows: Berg Balance Scale, 84% and 78%; balance subscale of the Tinetti Performance-Oriented Mobility Assessment, 68% and 78%; gait speed, 80% and 89%; and Tinetti Fall Efficacy Scale, 59% and 82%. The combination of two tests, Berg Balance Scale and gait speed, yielded the highest sensitivity of 91% and the highest specificity of 70% when a subject tested positive on at least one test. CONCLUSION AND DISCUSSION: These findings indicate the feasibility of developing screening methods for referring community-dwelling elderly individuals for a detailed physical therapy evaluation based on established clinical assessment measures, with a combination of tests measuring balance and gait demonstrating the most promising results.

Activities of Daily Living↗
PubMed1995

Physical therapy to improve functioning of older people in residential care facilities.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the effectiveness of an individualized physical therapy mobility training program on the gait, balance, and functional performance of elderly individuals living in residential care facilities. SUBJECTS: Twenty-seven elderly individuals with impaired balance and difficulty performing at least one functional activity participated in the study. The subjects ranged in age from 71 to 97 years (mean = 87.1, SD = 6.7). METHODS: Balance and gait speed were assessed at baseline and following physical therapy that consisted of exercises to improve specific functional limitations. Outcomes were reassessed 1 month following completion of the physical therapy. RESULTS: Gait and balance outcomes were analyzed using a one-way repeated-measures analysis of variance. Improvement was obtained in balance, which was maintained at 1 month follow-up. Gait speed did not improve to a level of statistical significance. CONCLUSION AND DISCUSSION: After physical therapy, subjects improved in balance and functional performance. An improvement in gait speed may require a longer duration of treatment.

Activities of Daily Living↗
PubMed1995

The effects of green tea catechins (Polyphenon) on DL-ethionine-induced acute pancreatitis.

The effects of green tea catechins (Polyphenon) on DL-ethionine-induced acute pancreatitis in rats were examined. The acute pancreatitis induced in this study was characterized by moderate inter- and intrastitial edema and patchy acinar cell necrosis. In rats induced with acute pancreatitis by an intraperitoneal injection of DL-ethionine, the wet weight of the pancreas (0.47 +/- 0.059 g/100 g body weight; p < 0.05), the serum amylase (10,432 +/- 996 IU/L; p < 0.001), and the tissue concentration of lipid peroxides (19.5 +/- 1.78 nmol/mg tissue DNA; p < 0.001) were significantly increased compared with values obtained in control rats (0.39 +/- 0.037 g/100 g body weight, 5,639 +/- 1,568 IU/L, and 10.7 +/- 1.04 nmol/mg tissue DNA, respectively) injected with isotonic saline. In contrast, in rats injected with DL-ethionine and supplied with a green tea catechin solution as a beverage instead of water during the experimental period, the tissue of pancreas was almost-correct, and the wet weight of the pancreas (0.39 +/- 0.054 g/100 g body weight; p < 0.05), the serum amylase (5,716 +/- 708 IU/L; p < 0.001), and the concentration of lipid peroxides in tissue (11.5 +/- 2.15 nmol/mg tissue DNA; p < 0.001) were significantly decreased compared with values obtained in rats injected with DL-ethionine and supplied with water as a beverage. These data suggest that green tea catechins may have a protective effect on the pathogenesis of experimental acute pancreatitis.

Acute Disease↗
PubMed1995

Molecular and epidemiological analyses of abnormal expression of aromatase in breast cancer.

One-third of human breast cancers exhibit estrogen-dependent proliferation. It appears that estrogen functions as a mitogenic factor in these carcinomas. As aromatase is the rate-limiting enzyme in estrogen biosynthesis. It could play an important role in the pathogenesis of estrogen-dependent breast cancer. The aromatase gene consists of at least six exons 1, each containing a promoter, and the tissue-specific expression is regulated by alternative use of these multiple promoters. The expression of aromatase in the breast and abdominal adipose tissues is regulated by a promoter flanking exon 1b. Molecular and epidemiological analyses of tissue-specific utilization of multiple exons 1 and promoters revealed a switching from use of the adipose-specific exon 1b to exon 1c in adipose tissues adjacent to the carcinomas in most breast cancer patients. Exon 1c has been shown to be specific for the ovary. Aromatase mRNA in adipose tissues distal to the tumour of the same patients was normally transcribed from exon 1b as was breast tissue in healthy controls. It is noteworthy that a switching from exon 1b to exon 1c was often observed in breast cancer patients having metastatic lymph nodes. These data suggest that switching from an adipose-specific exon 1b to exon 1c could cause a deviation from strict regulation of tissue-specific expression of the adipose aromatase leading to over-expression of the adipose aromatase. Consequently overproduction of local estrogen may promote carcinogenesis or proliferation of breast cancer cells.

Adipose Tissue↗