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Biomedical subjects

T Furukawa

Publications and source records attributed to T Furukawa.

At least 253 records · Page 14Linked to original sources
PubMed1997

Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation.

We have isolated a novel otx-like homeobox gene, Crx, from the mouse retina. Crx expression is restricted to developing and mature photoreceptor cells. CRX bound and transactivated the sequence TAATCC/A, which is found upstream of several photoreceptor-specific genes, including the opsin genes from many species. Overexpression of Crx using a retroviral vector increased the frequency of clones containing exclusively rod photoreceptors and reduced the frequency of clones containing amacrine interneurons and Müller glial cells. In addition, presumptive photoreceptor cells expressing a dominant-negative form of CRX failed to form proper photoreceptor outer segments and terminals. Crx is a novel photoreceptor-specific transcription factor and plays a crucial role in the differentiation of photoreceptor cells.

3T3 Cells↗
PubMed1997

Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor.

Genes associated with inherited retinal degeneration have been found to encode proteins required for phototransduction, metabolism, or structural support of photoreceptors. Here we show that mutations in a novel photoreceptor-specific homeodomain transcription factor gene (CRX) cause an autosomal dominant form of cone-rod dystrophy (adCRD) at the CORD2 locus on chromosome 19q13. In affected members of a CORD2-linked family, the highly conserved glutamic acid at the first position of the recognition helix is replaced by alanine (E80A). In another CRD family, a 1 bp deletion (E168 [delta1 bp]) within a novel sequence, the WSP motif, predicts truncation of the C-terminal 132 residues of CRX. Mutations in the CRX gene cause adCRD either by haploinsufficiency or by a dominant negative effect and demonstrate that CRX is essential for the maintenance of mammalian photoreceptors.

Adult↗
PubMed1997

Up-regulation of angiotensin type 2 receptor mRNA by angiotensin II in rat cortical cells.

The present experiment demonstrates that the exposure of angiotensin II (AII) produced an up-regulation of the AT2 receptor mRNA level in rat cortical cells. AII (10(-9)-10(-5) M) exerted a marked increase of AT2 receptor mRNA in a dose-dependent manner. The maximum increase was observed at 3 hr of AII stimulation and lasted 3 hr. The up-regulation of AT2 receptor mRNA was antagonized by PD123319, an AT2 receptor antagonist, but not by SC-52458, an AT1 receptor antagonist, thus suggesting that the increase in AT2 receptor mRNA is mediated via AT2 receptor. This increase is blocked by serine/threonine phosphatase inhibitor okadaic acid, but not by the phosphotyrosine phosphatase inhibitor sodium vanadate, thus suggesting the involvement of serine/threonine phosphatase in this process. Protein kinase C inhibitor, H-7 and calphostin C, did not inhibit the AII-induced up-regulation significantly. In addition, calcium ionophore, A23187 had no effect. These findings suggest that the AT2 receptor mRNA expression by AII is regulated by the activity of serine/threonine phosphatase in the cortical neurons. This observation is also the first example concerning the regulation of AT2 receptor within the brain.

Angiotensin II↗
PubMed1997

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

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

Adenocarcinoma↗
PubMed1997

Reversal of heavy metal resistance in multidrug-resistant human KB carcinoma cells.

Human KB carcinoma C-A120 cells that express multidrug resistance-associated protein (MRP) were cross-resistant to trivalent and pentavalent antimonials and arsenicals. Intracellular glutathione (GSH) content was higher in C-A120 than its parental KB-3-1 cell line. Glutathione-S-transferase (GST) was similar in both cell lines. Depletion of cellular GSH by treatment of the cells with the inhibitor of gamma-glutamylcysteine synthetase (gamma-GCS), buthione sulfoximine (BSO), significantly increased the sensitivity of both KB-3-1 and C-A120 cells to heavy metals. A pyridine analog, PAK-104P, almost completely reversed the resistance to antimonials and arsenicals in C-A120 cells. BSO at 100 microM or PAK-104P at 10 microM enhanced the accumulation of antimony potassium tartrate in C-A120 cells to the level of that in KB-3-1 cells without the agents. PAK-104P inhibited the ATP-dependent efflux of antimony potassium tartrate. These findings suggest that MRP transports antimony conjugated with GSH ATP-dependently outside the cells and PAK-104P inhibits the transporting activity of MRP.

ATP-Binding Cassette Transporters↗
PubMed1997

Function of P-glycoprotein expressed in placenta and mole.

We examined the expression of P-glycoprotein in human placentas and hydatidiform moles. Trophoblasts in all the examined placentas and moles expressed P-glycoprotein, and the size of the P-glycoprotein was smaller than that in multidrug-resistant human epidermoid carcinoma KB cells. The P-glycoprotein in the placenta and mole was photolabeled with [3H]azidopine, and [3H]vincristine was transported in an ATP-dependent manner into membrane vesicles prepared from trophoblasts that expressed P-glycoprotein. These findings indicate that P-glycoprotein expressed in trophoblasts has a drug binding site(s) and the ability to transport vincristine, suggesting that P-glycoprotein in the placenta protects the fetus from xenobiotics and confers drug resistance on moles.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Existence of dopamine D1 receptor on the sympathetic nerve endings in the guinea-pig vas deferens.

The effects of selective dopamine receptor agonists and antagonists on sympathetic neuromuscular transmission were investigated in the guinea-pig vas deferens in order to test for the presence of presynaptic dopamine receptors. A single-pulse field stimulus induced a rapid monophasic contraction which was strongly inhibited by alpha,beta-methylene ATP, a P2X purinoceptor desensitizing agent. The contraction was also inhibited by 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304), a selective alpha2-adrenoceptor agonist. This inhibition was antagonized by idazoxan, an alpha2-adrenoceptor antagonist, but not by R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaz epine hydrochloride (SCH-23390), a dopamine D1 receptor antagonist. Furthermore, the contractions were inhibited in a dose-dependent manner by R(+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF-38393) and (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-be nzazepine hydrobromide (SKF-82958), dopamine D1 receptor agonists, and the inhibition was antagonized by both SCH-23390 and idazoxan, but not by spiperone, a dopamine D2 receptor antagonist. The results suggest that dopamine D1 receptors are located on the sympathetic nerve endings of guinea-pig vas deferens.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Involvement of the transcriptional factor GATA-1 in regulation of expression of coproporphyrinogen oxidase in mouse erythroleukemia cells.

Coproporphyrinogen oxidase (CPO; EC 1.3.3.3), the sixth enzyme of heme biosynthesis, transcribed from a single promoter is markedly induced during erythroid differentiation. CPO is ubiquitously expressed in all cells. To determine cis-acting elements of the human CPO gene, the promoter region of the gene was isolated, and three potential GATA-1 motifs and four GC boxes were found within this fragment. In a functional analysis of various deletion mutants, we found that the GATA-1 binding site at -143 to -138 was essential for basic and inducible expressions of the CPO gene in mouse erythroleukemia (MEL) cells. Gel mobility shift assay revealed that GATA-1 bound to the region is required for the expression and this was confirmed by observations that the nuclear protein bound to the GATA-1 motif was supershifted with anti GATA-1 antibody, by gel mobility shift assay. Furthermore, co-expression of mouse GATA-1 in MEL cells led to an increase in the promoter activity, which was markedly increased by dimethyl sulfoxide-treatment. These results indicate that GATA-1 plays an important role in regulation of transcription of the CPO gene in erythroid cells.

Animals↗
PubMed1997

rax, a novel paired-type homeobox gene, shows expression in the anterior neural fold and developing retina.

Development of the vertebrate eye has been found to require the activity of several genes encoding homeodomain proteins (Freund, C., Horsford, D. J. & McInnes, R. R. (1996) Hum. Mol. Genet. 5, 1471-1488). Some of these genes, or portions thereof, are highly conserved across phyla. In this paper, we report the identification of a novel homeobox gene, rax (retina and anterior neural fold homeobox), whose expression pattern suggests an important role in eye development. The predicted amino acid sequence of Rax comprises a protein with a paired-type homeobox, as well as the octapeptide that is found in many paired-type homeobox genes. In addition, in the C terminus of Rax, we found a 15-aa domain that we have named the OAR domain. This domain is also found in several other homeobox genes. In the early mouse embryo, rax is expressed in the anterior neural fold, including areas that will give rise to the ventral forebrain and optic vesicles. Once the optic vesicles form, rax expression is restricted to the ventral diencephalon and the optic vesicles. At later stages, rax expression is found only in the developing retina. After birth, the expression of rax is restricted to the zone of proliferating cells within the retina, and expression gradually decreases as proliferation declines. These findings suggest that rax is one of the molecules that define the eye field during early development and that it has a role in the proliferation and/or differentiation of retinal cells.

Amino Acid Sequence↗
PubMed1997

Laboratory diagnosis of anemia and related diseases using multivariate analysis.

To establish a simple computer program for the laboratory diagnosis of anemia and related diseases, multivariate analyses were applied to the results of routine hematological laboratory tests obtained from 48 patients and 51 healthy volunteers. The patients studied were limited to those who had not been treated hematologically by the time of their first visit to our hospital, and their first data obtained in our laboratory were analyzed. Final diagnoses were aplastic anemia (AA) in 21, myelodysplastic syndrome (MDS) in 14, iron deficiency anemia (IDA) in 3, polycytemia vera (PV)in 3, and idiopathic thrombocytopenic purpura (ITP) in 7. Eight parameters, WBC, RBC, Hb, Ht, MCV, MCH, MCHC, and PLT, were transformed to normal distribution and then applied to principal component analysis to evaluate their independence. Very close relationships were observed between Ht and Hb, and between MCV and MCH. One each of these pairs was selected by discriminant analysis and two sets, RBC, MCH, Hb, PLT, and WBC, and RBC, MCV, Ht, PLT, and WBC, were obtained. Two canonical components gave good discrimination of these five diseases and also of normal subjects. When disease prediction was made using this analysis, 37 of 48 patients (77.1%) were predicted correctly, and furthermore, when two disease predictions were allowed, all patients were diagnosed properly. Some overlaps were observed in this two-dimensional coordinate system, especially of AA and MDS, and also with normal subjects. To improve the system further, the additional parameters of age and sex were added to construct a three-dimensional analysis which resulted in much clearer discrimination. The whole procedure described is being developed with subjects who are not taking medication. Subsequently, the general application of this analytical procedure should be limited to only those not on medications. In conclusion, this is in essence a demonstration project; however, this trial of laboratory diagnosis using routine hematological laboratory results appears to be promising. Further extension of the study by increasing numbers of patients and disorders studied, including secondary anemias, will allow the design of diagnostic software for use with personal computers at the sites of primary care.

Adult↗
PubMed1997

Frequent gain of copy number on the long arm of chromosome 20 in human pancreatic adenocarcinoma.

We have used comparative genomic hybridization (CGH) to survey genomic regions with aberrant copy numbers of DNA sequences in pancreatic adenocarcinoma. In 12 cell lines and 6 primary tumors from 18 patients with pancreatic adenocarcinomas, highly frequent losses (> 60%) were observed on chromosome arms 6q, 9p, and 18q and the Y chromosome. Moderately frequent losses (40-60%) were observed on chromosome arms 3p, 4q, 8p, and 21q. Interestingly, these samples showed extremely high frequencies of increases in copy numbers of DNA sequences on the long arm of chromosome 20 (15/18, 83%). We further analyzed five cell lines by fluorescence in situ hybridization (FISH) with probes on chromosome 20 to define the increase in copy number more accurately, and we found that 20q was increased to between 5 and 8 copies per cell. These results suggest the existence of an oncogene or oncogenes in 20q that play a role in the development and/or the progression of pancreatic carcinogenesis.

Adenocarcinoma↗
PubMed1997

The continuous and simultaneous blood flow velocity measurement of four cerebral vessels and a peripheral vessel during cigarette smoking.

There has been no consensus about the acute effect of cigarette smoking on cerebral blood flow, and the continuous change of flow in four cerebral vessel flow with peripheral flow during different kinds of cigarette smoking has not been reported until now. Our results indicate smoking increases the flow of four cerebral vessels almost at the same time and with the same pattern. Many cerebral vessels began to show increases about 10 s after commencement. In most cases, cerebral blood velocity began to decrease between 10 and 20 s after cessation. Blood flow in peripheral vessels decreases after commencement, which is thought to be the effect of nicotine. The effect of high nicotine cigarettes is greater than that of low nicotine cigarettes. Continuous and simultaneous measurement of cerebral vessels by ultrasonic Doppler is though to be the only way to establish the detailed blood flow changes during smoking.

Adult↗
PubMed1997

Dissociations between reading responses and semantic priming effects in a dyslexic patient.

We report a patient (Y.Y.) with senile dementia of the Alzheimer's type. The patient read aloud some words composed of two or three kanji characters with errors applying typical pronunciations of each character and defined them in keeping with the mispronunciation if the pronunciation represented another real word. The results of single-word semantic priming in a lexical decision task, however, suggested normal recognition processes for these kanji-words, despite the patient's reading errors. We consider her reading to represent surface dyslexia in Japanese. We discuss these dissociations between reading responses and priming effects in the context of dual-route models of human reading, and conclude that the "visual route" (direct access from orthography to semantics and phonology) was not completely disrupted, but partially preserved and functioning in automatic access.

Aged↗
PubMed1997

Intraductal ultrasonography in diagnosing tumor extension of cancer of the papilla of Vater.

BACKGROUND: Intraductal ultrasonography is clinically useful in assessing various pancreatobiliary diseases. This study was carried out to evaluate the usefulness of intraductal ultrasonography in diagnosing tumor extension of cancer of the papilla of Vater. METHODS: Thirty-two patients with cancer underwent intraductal ultrasonography. According to the spatial relationship between the tumor echo and the hypoechoic layers representing Oddi's muscle layer or the duodenal muscularis propria layer, the images were classified into four grades. We attempted to diagnose tumor extension using this grading system. Lymph nodes measuring over 10 mm were evaluated as involved. Findings were compared with postoperative histopathologic findings classified as follows: d0, tumor limited to Oddi's muscle layer; d1, tumor invading the duodenal submucosal layer; d2, tumor invading the duodenal muscularis propria layer; and panc(+), tumor invading the pancreas. RESULTS: Diagnostic accuracy rate was 100% (6 of 6) in d0 cases, 92.3% (12 of 13) in d1 cases, 100% (1 of 1) in a d2 case, and 75% (9 of 12) in panc(+) cases. Overall accuracy rate was 87.5% (28 of 32). In assessing lymph node metastases, sensitivity was 66.7% (6 of 9) and specificity was 91.3% (21 of 23). CONCLUSION: Intraductal ultrasonography examination is useful in diagnosing tumor extension of cancer of the papilla of Vater.

Adult↗
PubMed1997

Application of the Center for Epidemiologic Studies Depression Scale among first-visit psychiatric patients: a new approach to improve its performance.

BACKGROUND: Although the Center for Epidemiologic Studies Depression Scale (CES-D) is an internationally popular self-rating scale for depression both in community and clinical settings, extant literature concerning its validity has several shortcomings. The present paper aimed to overcome these problems. METHODS: We applied newer assessment technology of receiver operating characteristics (ROC) analyses and stratum-specific likelihood ratios (SSLRs) and cross-validated the results in the 'training' and 'testing' data sets of 591 patients representing various clinical settings all over Japan. RESULTS: The ROC analyses demonstrated that the CES-D had moderate convergent and discriminant validity to detect major depressive episodes among first-visit psychiatric patients. Selecting single optimal cutoffs, however, failed to arrive at consistent results across various settings. The efficacy of the instrument was most conveniently transportable into clinical practices when converted into SSLRs, which were 0.35 (95% CI: 0.25-0.49) for the score range 0-29, 2.3 (1.8-3.1) for the score range 30-49, and 11.7 (3.1-44.0) for the scores above 50. In addition, the SSLRs proved to be generalizable not only across various clinical settings in our sample but also across psychiatric, primary care and community samples in the published reports. CONCLUSION: Clinicians and clinical epidemiologists can apply the SSLRs of the CES-D to various settings to estimate the probability of suffering from a major depressive episode in a convenient and intuitive manner.

Comorbidity↗
PubMed1997

Nitric oxide, 2-amino-4-phosphonobutyric acid and light/dark adaptation modulate short-wavelength-sensitive synaptic transmission to retinal horizontal cells.

Light-induced changes in the input resistance (Rin) of external, luminosity (i.e. H1) type horizontal cell (HC) perikarya were studied by the bridge-balance method in light-adapted and dark-adapted retinae of carp. Changes in input resistance (delta Rin) induced by short-(460 nm) and long-wavelength (674 nm) flashes, adjusted in intensity to elicit equal-amplitude membrane voltage responses (equal-voltage condition), were measured. In light-adapted retinae, long-wavelength stimuli increased Rin consistently; in contrast, the increase was much less with short-wavelength stimuli. This equal-voltage chromatic delta Rin difference was lost in dark-adapted retinae whereby the delta Rin (an increase) became the same for short- and long-wavelengths. The chromatic delta Rin difference could be recovered by light adaptation or application of sodium nitroprusside to the dark-adapted retinae. Conversely, the equal-voltage chromatic delta Rin difference was eliminated by injection of NG-monomethyl-L-arginine into H1HCs of the light-adapted retinae or by treating the retinae with 2-amino-4-phosphonobutyrate (APB). These results suggest that H1HCs of the carp retina possess distinct postsynaptic mechanisms which mediate short- and long-wavelength signal transmission. Furthermore, it appears that the short-wavelength-sensitive pathway is active only during the light-adapted state of the retina. Taken together, therefore, the short-wavelength transmission to H1HCs probably operates on an APB-sensitive glutamate receptor, with nitric oxide as a light-adaptive messenger.

Acclimatization↗