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Biomedical subjects

K Suyama

Publications and source records attributed to K Suyama.

At least 19 recordsLinked to original sources

Limited suppression of prostate-specific antigen after salvage radiotherapy for its isolated elevation after radical prostatectomy.

OBJECTIVES: To investigate the clinical outcome and degree of prostate-specific antigen (PSA) suppression after salvage radiotherapy performed because of isolated PSA elevation after radical prostatectomy. METHODS: We examined the outcomes of 32 patients who underwent radiotherapy after radical prostatectomy. Hypersensitive, as well as conventional, PSA assays were used to measure PSA levels after irradiation. RESULTS: Of 125 patients who underwent radical prostatectomy for clinically resectable prostate cancer, 42 (33.6%) developed detectable PSA an average of 13.5 months postoperatively. Thirty-two patients underwent salvage radiotherapy. In 13 patients (40.6%), PSA became undetectable (less than 0.1 ng/mL) at a mean of 1.2 months. Two of these patients later developed detectable PSA within 1 2 months. Of 22 patients who had at least 12 months of follow-up, 8 had a durable PSA response. Of 13 patients who attained an undetectable PSA postoperatively and then showed a delayed progressive increase, 7 exhibited a durable response lasting for more than the 12 months after irradiation. By contrast, only 1 of 9 patients with persistently elevated postoperative PSA showed undetectable levels after irradiation. Frozen sera from the 8 patients with a durable response to irradiation were available to measure levels less than 0.1 ng/mL by hypersensitive assay. The mean value was 0.035 ng/mL at an average of 26.9 months after irradiation. Only 3 patients had levels less than 0.01 ng/mL. CONCLUSIONS: Although radiotherapy may be beneficial in a small number of patients, many patients continue to have measurable levels of PSA (more than 0.01 ng/mL) after irradiation. Our results suggest that this treatment in its current form is inadequate to eradicate residual carcinoma.

Aged

Diagnostic value of plasma levels of brain natriuretic peptide in arrhythmogenic right ventricular dysplasia.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by local or diffuse wall motion abnormalities in the right ventricle (RV), associated with recurrent ventricular tachycardia (VT) of RV origin. Brain natriuretic peptide (BNP) was first isolated from a porcine brain extract. In humans, BNP is expressed predominantly in the ventricles of failing hearts, and its expression has been observed primarily in myocytes in the interstitial fibrous area in dilated cardiomyopathy. We hypothesized that BNP is increasingly secreted from the residual myocytes within the atrophic tissue in patients with ARVD. METHODS AND RESULTS: Plasma BNP levels were measured in 17 patients with ARVD, 12 patients with idiopathic RV outflow tract tachycardia (RVOT), and 120 control subjects. We performed cardiac catheterization, RV endomyocardial biopsy, electron- beam CT, and biventricular endomyocardial mapping in the ARVD patients. There was a significant increase in plasma BNP levels in the ARVD patients compared with the RVOT patients and control subjects (61.4+/-59.6 pg/mL versus 8.3+/-5. 5 pg/mL and 9.3+/-5.8 pg/mL; P<0.0001, respectively). The plasma BNP levels had no correlation with any of the hemodynamic data, but they had a significant correlation with the RV ejection fraction (r=-0. 588, P=0.025) and with the fractionated-area scores (r=0.705, P=0. 005). Light microscopic immunohistochemistry showed strong BNP immunoreactivity in residual myocytes with fibrofatty replacement. CONCLUSIONS: These results suggest that plasma BNP levels were not increased in RVOT patients but were increased in ARVD patients, and that the increased BNP levels indicate the severity of both the RV dysfunction and the arrhythmogenic substrate.

Adolescent

Clinical and electrophysiologic features of idiopathic left ventricular aneurysm with sustained ventricular tachycardia.

We examined 10 patients with idiopathic left ventricular (LV) aneurysm with sustained ventricular tachycardia (VT) (Id-An group), and compared them with those in 16 age- and sex-matched patients who had postinfarction aneurysm and VT (MI-An group) to clarify detailed clinical and electrophysiologic characteristics of idiopathic LV aneurysm. The clinical and laboratory data and results of electrocardiography, electrophysiologic, and morphologic examinations in the two groups were compared. In the Id-An group, the LV aneurysms were located more often at the posterior and/or inferior wall, while in the MI-An group, they were more often located at the anterior and/or apical wall (P<0.001). The LV end-diastolic volume index was significantly smaller and the LV ejection fraction was significantly higher in the Id-An group (P<0.001). The size of the aneurysm and the area with abnormal electrograms in the Id-An group were significantly smaller than those in the MI-An group (P<0.005 and P<0.001, respectively). The inducibility of VT was high in both groups, and ventricular pacing during VT showed entrainment phenomenon in most of the patients. Thus, in both groups, the abnormal electrograms were closely associated with the wall motion abnormality, and reentry was suggested as the mechanism of VT. In the Id-An group, since the lesions were anatomically and electrophysiologically confined to the posterior and/or inferior wall, the global LV function was more well preserved compared with the MI-An group.

Cardiac Catheterization

Localization of optimal ablation site of idiopathic ventricular tachycardia from right and left ventricular outflow tract by body surface ECG.

BACKGROUND: Idiopathic ventricular tachycardia (VT) is known to arise from the right ventricular (RV) and left ventricular outflow tracts (LVOT). However, reliable noninvasive methods to localize the optimum ablation site for VT have not been reported. METHODS AND RESULTS: Body surface maps (BSM) and 12-lead ECGs were investigated in 35 VTs from the RVOT and 5 VTs from the LVOT in which the origin was confirmed during the ablation procedure. The RVOT was classified into 8 subdivisions with the use of a 3-dimensional anatomic relation: anterior (A) posterior (P), right (R) left (L), and superior (S) inferior (I). On the BSM, the following 3 indexes differentiated each location of the origin, with a diagnostic accuracy of 88% (A-P), 92% (R-L), and 77% (S-I): (1) the location of the minimum at the early-to-mid QRS (right, A; left, P), (2) the isopotential distribution in the left shoulder area after 30 ms of QRS (positive, R; negative, L), and (3) the downward moving time of the minimum at the early-to-mid QRS (>/=50 ms, S; <50 ms, I). On the 12-lead ECG, (1) the QRS duration (>140 ms, A; </=140 ms, P) and the R-wave pattern in leads II and III (RR' or Rr', A, R, P), (2) the QS wave amplitude in aVR and aVL (aVR>/=aVL, R; aVR /=1 in lead V3 was an index suggesting the LVOT origin. CONCLUSIONS: The origin or the optimum ablation site of idiopathic VT from RVOT and LVOT can be localized with the use of indexes obtained with a BSM or 12-lead ECG.

Adolescent

Improvement of repolarization abnormalities by a K+ channel opener in the LQT1 form of congenital long-QT syndrome.

BACKGROUND: This study used monophasic action potential (MAP) to examine the effect of nicorandil, a K+ channel opener, on repolarization abnormalities induced by epinephrine in the LQT1 form of congenital long-QT syndrome in which the KvLQT1 mutation underlies the defect in the channel responsible for the slowly activating component of the delayed rectifier potassium current. METHODS AND RESULTS: MAPs were recorded simultaneously from two or three sites on the right ventricular and left ventricular endocardium in 6 patients with a congenital form of LQT1 syndrome with KvLQT1 defect (17 sites) and 8 control patients (24 sites). In LQT1 patients, epinephrine infusion prolonged the QT interval and 90% MAP duration (MAPD90) and increased the dispersion of MAPD90. Epinephrine also induced early after depolarizations (EADs) as well as ventricular premature complexes (VPCs) in 2 of the 6 patients. Nicorandil during epinephrine infusion abbreviated the QT interval and MAPD90, decreased the dispersion of MAPD90, and abolished the EADs as well as the VPCs in 1 patient. Addition of propranolol completely reversed the effect of epinephrine in prolonging the QT interval and MAPD90 and increasing the dispersion and eliminated the EADs and VPCs in another patient. In control patients, the effect of epinephrine and that of additional nicorandil and propranolol on repolarization parameters were much less than in the LQT1 patients. CONCLUSIONS: Our results suggest that nicorandil, a K+ channel opener, improves repolarization abnormalities in the LQT1 form of congenital long-QT syndrome with KvLQT1 defect.

Adolescent

Intravascular ultrasound evaluation of plaque distribution at curved coronary segments.

Although the distribution of atherosclerosis at the curved coronary segments has implications for atherogenesis and interventional procedures, few data exist regarding the plaque distribution in these sites. Therefore, we prospectively analyzed the intravascular ultrasound images of 55 coronary sites from 37 patients where the atherosclerotic plaque and pericardium were simultaneously demonstrated by intravascular ultrasound. The pericardial images were defined as a high-intensity linear echo image moving during cardiac cycles outside the vessel wall. By the line that was parallel to the pericardial image, the vessel area was divided into 2 semicircles with the same area, namely myocardial and pericardial sides. In each side, the maximal thickness, area, and percent area of plaque were measured. The plaque thickness and area of the myocardial side were significantly greater (1.5 +/- 0.5 mm, 4.9 +/- 2.1 mm or 66%, mean +/- SD) than those of the pericardial side (1.1 +/- 0.4 mm, 3.5 +/- 2.1 mm2 or 45%, p < 0.01). The maximal plaque thickness was positioned at the point with a mean angle of 139 +/- 37 degrees from the point just facing the pericardial image, indicating that atherosclerosis was eccentrically located on the opposite side of the pericardium in these coronary segments, and suggesting that the side of the pericardial image represents the outer curvature of the coronary artery. These results indicate that the pericardial images can be seen by intravascular ultrasound, facilitating the recognition of the disease distribution in situ. The eccentric plaque located on the inner wall at the curved coronary segments, probably due to uneven local shear stress, may have implications for the interventional procedures for these segments.

Aged

Recovery and refining of Au by gold-cyanide ion biosorption using animal fibrous proteins.

Animal fibrous proteins (AFPs) such as egg-shell membrane (ESM), chicken feather (CF), wool, silk, or elastin are an intricate network of stable and water-insoluble fibers with high surface area and are abundant bioresources. Every AFP tested was found to accumulate gold-cyanide ion from aqueous solutions in high yield, depending on pH and some other parameters. Gold-cyanide ion is adsorbed by AFP at low pH range, with maximum binding observed at approx pH 2.0. Under the certain conditions, gold-cyanide ion was accumulated up to 8.6, 7.1, 9.8, 2.4, and 3.9% of dry weight on ESM, CF, wool, silk, and elastin, respectively. In the case of ESM, it was found that ESM removed gold-cyanide ion almost quantitatively and almost all the gold uptake by ESM was easily desorbed with 0.1 M NaOH. ESM can be used repeatedly for the process of gold adsorption-desorption. The gold-biosorptive capacity of ESM that was chemically modified with glutaraldehyde was higher than that of control. In column procedure, ESM packed on column removed gold-cyanide ion from the dilute aqueous solution to extremely low concentrations (nondetectable concentration of below 1 ppb).

Adsorption

Clinical and pathological significance of the level and extent of capsular invasion in clinical stage T1-2 prostate cancer.

This study was performed to assess the relationship between the level and extent of prostatic capsular invasion (PCI) by cancer and the clinical and pathological features and prognosis of early-stage prostate cancer. We conducted a retrospective analysis of the clinical (age, stage, grade, prostate specific antigen [PSA] level) and pathological (tumor volume, stage, grade, surgical margins) features of 688 patients treated with radical prostatectomy to determine the pathological features and probability of recurrence associated with various levels of PCI. Radical prostatectomy specimens were serially sectioned and examined by whole-mount technique. Progression-free probabilities (PFP) after radical prostatectomy were determined by Kaplan-Meier and Cox proportional hazards regression analysis. Progression was defined as a rising serum PSA < or = 0.4 ng/mL or clinical evidence of recurrent cancer. Increasing clinical stage, Gleason grade in the biopsy specimen, and pretreatment serum PSA levels were each associated with increasing levels of PCI (P < .001). In the radical prostatectomy specimen, increasing levels of PCI were significantly associated with increasing tumor volume (P < .001), Gleason grade (P < .0001), seminal vesicle involvement (SVI, P < .001) and lymph node metastases (+LN, P < .001). None of 138 patients without capsular invasion had SVI or lymph node metastases (+LN), and all remained free of progression, even though some had large volume (up to 6.26 cm3) or poorly differentiated (Gleason sum up to 8) cancers. Invasion into the capsule (n = 271) was occasionally associated with SVI (6%) or +LN (3%) and a significantly (log-rank test) lower PFP of 87% at 5 years. Focal and extensive extraprostatic extension (EPE) were associated with progressively increased risk of SVI and +LN and lower PFP (73% and 42%, respectively). In a multivariate analysis, the level of PCI was an independent prognostic factor (P < .001). There is a strong association between the level of invasion of cancer into or through the prostatic capsule and the volume, grade, pathological stage, and rate of recurrence after radical prostatectomy. Prostate cancer does not appear to metastasize in the absence of invasion into the capsule regardless of the volume or grade of the intracapsular tumor. Subclassification of patients according to the levels of PCI provides valuable prognostic information.

Adenocarcinoma

Inadequacy of free prostate-specific antigen parameters in the prediction of pathologic extent of prostate cancer in Japanese men.

OBJECTIVES: To evaluate free prostate-specific antigen (PSA) and free to total PSA ratio as predictors of pathologic extent in Japanese patients with prostate cancer. METHODS: By TOSOH assay, pretreatment serum serologic markers of free PSA, total PSA, free to total PSA ratio, and PSA density (PSAD) were determined for 108 patients subsequent to radical prostatectomy for resectable prostate cancer. Serum values for these markers were compared with pathologic findings and tumor volume on the basis of pathologic assessment of whole mount section histology. RESULTS: Mean total PSA, free PSA, free to total PSA ratio, and PSAD significantly differed for pathologically confined (pT2 or lower) and advanced (pT3 or higher) cancers (P < 0.05). Total PSA, free PSA, and PSAD provided indication of seminal vesicle involvement, surgical margin status, nodal involvement, and total tumor volume (P < 0.05). Free PSA was more closely correlated with total tumor volume than the free to total PSA ratio; this ratio was not correlated with total tumor volume or specimen Gleason score. Free PSA and free to total PSA ratio were not found to be any more useful than total PSA and PSAD for predicting pT3 disease by receiver operating characteristic curve analysis. Multivariate logistic regression analysis and log likelihood ratio test results indicated little additional value of these parameters for predicting pT3 disease. CONCLUSIONS: Contrary to previous reports, free PSA and the free to total PSA ratio are of little use subsequent to the diagnosis of prostate cancer.

Adult

Improved predictability of extracapsular extension and seminal vesicle involvement based on clinical and biopsy findings in prostate cancer in Japanese men.

OBJECTIVES: The accurate preoperative prediction of the extent of cancer by pathologic examination is essential for choosing the optimal treatment for patients with prostate cancer. Currently available clinical staging methods are not adequate and more precise staging is required. METHODS: Using the log likelihood ratio test and receiver operating characteristic (ROC) curve analysis, preoperative variables, including biopsy pathologic findings, were assessed for predicting final pathologic stage in prostate cancer. A multivariate model for predicting disease organ confinement status was established for easy clinical use. RESULTS: The use of the number of cores with cancer and maximum cancer length in conjunction with the three variables (prostate-specific antigen, clinical stage, and biopsy Gleason score) was found to significantly improve predictability of extracapsular extension and seminal vesicle involvement in clinically resectable (n = 96) and localized prostate cancers (n = 81) (P < 0.05). Areas under ROC curves for the above two parameter sets (five- versus three-variable model) were 0.8395 and 0.7109, respectively, for capacity for extracapsular extension prediction in clinically localized cancer. These values for seminal vesicle involvement were 0.7861 and 0.6927, respectively. The logistic model gave positive and negative predictive values of 73% and 78%, and 64% and 83%, respectively, for extracapsular extension and seminal vesicle involvement in clinically localized cancer at a predicted probability of 0.5 or greater. CONCLUSIONS: The present method may be used to predict non-organ-confined prostate cancer with greater accuracy than the previously reported model using three variables.

Aged

Anoxic depolarization determines ischemic brain injury.

To clarify the role of anoxic depolarization (AD) in ischemic brain injury, we examined the correlation between AD and ischemia-induced neuronal injury. Twenty-eight rats underwent transient forebrain ischemia with lowering of blood pressure and bilateral carotid occlusion while direct current shifts, electrocorticogram, and cortical blood flow (CoBF) were epidurally recorded from the right parietal cortex. One week later the right parietal cortex was studied histopathologically. AD appeared 0.5-3.0 min after carotid occlusion in 21 of 28 animals. Circulation was reinitiated 15 min after AD onset in 11 rats (group A) and 10 min after onset in 10 rats (group B). AD did not develop during 20 min of ischemia in 7 rats (group C). All 12 rats (6 from group A and 6 from group B) in which CoBF decreased below 9.5% of control flow exhibited AD. Histopathologic examination disclosed massive neuronal necrosis in 5 of the 6 group A animals with marked flow reduction but in none from group B. CoBF fell between 9.5% and 20% in 14 rats, among these, AD appeared in 9 (5 from group A and 4 from group B) but not in 5 (group C). Massive neuronal necrosis was demonstrated in 3 of 5 rats from group A. Ischemic neuronal changes were absent or minimal in only 1/5 of group A animals, a much lower fraction than in group B (4/4, p < 0.05) or in group C (5/5, p < 0.05). When CoBF remained above 20% of control flow during ischemia (2 rats) no AD or irreversible injury occurred. The present study suggests that AD is a more reliable determinant of irreversible brain injury than degree of CBF reduction, and also demonstrates that 15 min is the critical duration of AD for irreversible brain injury at brain temperatures around 37 degrees C.

Animals

Public awareness and knowledge of prostate cancer in Japan: results of a survey at short-stay examination facilities.

BACKGROUND: This study was undertaken to determine public awareness and knowledge of prostate cancer, which has not been adequately studied in Japan. METHODS: Assessment was made of public awareness and perception of prostate cancer in Japan, based on health examination data for participants in a short-stay physical examination program ("human dry dock"). A multiple-choice, thirty-point questionnaire survey was conducted at 3 "human dry dock" medical facilities situated in urban areas. RESULTS: Many Japanese adults appeared to be inadequately aware of prostate cancer and of the means available for its early detection. One third of the participants were unfamiliar with this malignancy. Logistic regression analysis indicated smoking to be the only covariate associated with lack of knowledge of prostate cancer (P< 0.05). Seventy-one percent of the subjects had heard of digital rectal examination, but only 16% and 8%, respectively, were familiar with the terms transrectal ultrasonography and PSA testing. Japanese people may possibly be less informed about prostate cancer than African-American males. Both "human dry dock" facilities and subject gender were significantly associated with knowledge of digital rectal examination (P< 0.05). Knowledge of transrectal ultrasonography was found to depend on participation in "human dry dock" programs and level of education (P< 0.05). Smoking, participation in "human dry dock" programs under employer direction, and health status were all identified as determinants for knowledge of PSA testing (P< 0.05). CONCLUSION: Educational programs should be established and put into effect to instill adequate awareness of prostate cancer in Japan. In a better-informed society, more effort would be directed toward prevention and thus early stage prostate cancer would be detected more often.

Adult

Radiofrequency catheter ablation of concealed atrioventricular accessory pathways using a "simultaneous pacing method".

The retrograde atrial potential at a successful ablation site is usually obscured by the wide and large ventricular potential during atrioventricular reentrant tachycardia or ventricular pacing, which makes it difficult to determine the appropriate ablation site for a concealed accessory pathway. A pacing maneuver named the "simultaneous pacing method" is proposed herein to differentiate the retrograde atrial potential from the ventricular potential for a successful ablation of the concealed accessory pathway. Catheter ablation was performed in 12 patients with a single left free-wall concealed accessory pathway. The atrial insertion site was determined by the simultaneous pacing method in six patients (group I) and by ventricular pacing in six patients (group II). In the simultaneous pacing method, electrograms recorded during ventricular pacing in the earliest retrograde atrial activation site are a fusion of the ventricular potential and the following retrograde atrial potential. When atrial and ventricular pacings are performed simultaneously (simultaneous pacing), the end portion of the electrograms recorded at the same site is solely the ventricular component, because atrial is activated earlier. The atrial potential can be confirmed during ventricular pacing in comparison with the electrograms during the "simultaneous pacing." Radiofrequency catheter ablation was successful in eliminating conduction through the accessory pathway in all 12 patients. The radiofrequency applications in group I were significantly fewer than those in group II (1.7 +/- 1.0 in group I, 5.3 +/- 3.2 in group II, P < 0.05). The total procedure time in group I was significantly shorter than in group II (57.8 +/- 15.7 vs 106.7 +/- 41.6 mins in group II, respectively, P < 0.05). The fluoroscopy time in group I was significantly shorter than in group II (54.0 +/- 7.9 vs 81.3 +/- 26.3 mins, respectively, P < 0.05). We were able to determine the atrial insertion site of accessory pathways by the simultaneous pacing method. The simultaneous pacing method was useful in eliminating concealed left free-wall accessory pathways.

Adult

Mid-diastolic potential is related to the reentrant circuit in a patient with verapamil-sensitive idiopathic left ventricular tachycardia.

We report a case of verapamil-sensitive idiopathic ventricular tachycardia in which a mid-diastolic potential (MDP) 45 msec preceding the Purkinje potential (P potential) was recorded. Pacing during the tachycardia caused concealed entrainment, and the stimulus-QRS interval was equal to the P potential-QRS interval. The interval between the last pacing stimulus and the next P potential (postpacing interval) was longer than the ventricular tachycardia cycle length, but the MDP was orthodromically activated. These findings suggest that the MDP was on the reentrant circuit and the P potential was not on the reentrant circuit, but a bystander.

Adult

Increased dispersion of repolarization time determined by monophasic action potentials in two patients with familial idiopathic ventricular fibrillation.

INTRODUCTION: The role of increased dispersion of repolarization in the genesis of torsades de pointes in patients with long QT syndrome has been clarified, but its role in the genesis of idiopathic ventricular fibrillation (VF) is not yet known. To investigate the pathogenesis of VF, we recorded monophasic action potentials (MAPs) from two siblings (48- and 36-year-old males) with familial idiopathic VF. METHODS AND RESULTS: The elder brother (patient 1) showed a late r' wave in lead V1 and ST segment elevation in leads V1 through V3. The younger brother (patient 2) had late r' waves and ST segment elevation in leads II, III, and aVF, and the configurations were very similar to those of patient 1. MAPs were recorded from several sites in the right ventricular (RV) and left ventricular (LV) endocardium during constant right atrial pacing. The repolarization time (RT) was defined as the sum of the activation time (AT) and action potential duration (APD) at 90% repolarization. In patient 1, marked prolongation of the AT (140 msec) and the RT (380 msec) was recorded in the RV septum of the outflow tract, and the RT dispersion was markedly increased (125 msec). In contrast, patient 2 showed prolongation of the AT (80 msec) and RT (310 msec), and fractionated electrograms in the RV floor of the inflow tract. The RT dispersion was also increased (80 msec). VF and nonsustained polymorphic ventricular tachycardia were induced by double premature stimulation in patients 1 and 2, respectively. Chronic amiodarone therapy decreased the RT dispersion and suppressed the induction of ventricular tachyarrhythmias in patient 2, although late r' waves and slight ST segment elevation were unmasked in leads V1 and V2. CONCLUSION: Our data suggest that the increased dispersion of the RT, which was due mainly to a localized conduction delay in the RV, created an arrhythmogenic substrate in the two patients with familial idiopathic VF.

Action Potentials

Expression of the Rh-related glycoprotein (Rh50).

The Rh50 glycoprotein is suspected of being involved in Rh antigen expression. We prepared Rh50 cDNA from a human bone marrow library by polymerase chain reaction and then subcloned this cDNA into various vectors. The vector containing Rh50 cDNA produced a 30-kDa nonglycosylated form of Rh50 in a rabbit reticulocyte lysate system and produced partially glycosylated Rh50 (32 kDa) when microsomes were added to the system. COS-1 cells transiently transfected with the vector containing Rh50 cDNA produced partially glycosylated Rh50 (32 kDa) recognized by a Rh50-specific antibody. Surface expression of Rh50 in K562 cells was also detected by flow cytometry using mouse monoclonal antibody (2D10) specific to Rh50. Partially glycosylated Rh50 (32 kDa) was again isolated from the lysates of K562 cells metabolically labeled with [35S]-methionine or [3H]-mannose using anti-Rh50 antisera. These systems (K562 and COS-1 cells) should prove useful for studying the transport of Rh proteins within the cell and the necessary components needed for Rh antigenicity at the cell surface.

Animals

Gene expression and specific binding of platelet-derived growth factor and its effect on DNA synthesis in human decidual cells.

To clarify the biological significance of platelet-derived growth factor (PDGF) in human decidual cell function, which is important for the maintenance of pregnancy, we investigated gene expression of the PDGF subunits, PDGF-A and PDGF-B, specific binding of the PDGF isoform, and the effect of PDGF dimers on DNA synthesis in human decidual cells. We detected in decidua from early pregnancy the expected DNA bands of PDGF-A and PDGF-B by reverse transcriptase-polymerase chain reaction (RT-PCR) as well as mRNAs of each PDGF subunit by Northern blot hybridization, demonstrating that both PDGF subunits exist in this tissue. Scatchard plot analysis showed that decidual cells had both PDGF-alpha and PDGF-beta receptors. PDGF-AA, -AB and -BB stimulated [3H]-thymidine incorporation in cultured decidual cells in a dose-dependent manner. These results indicate the importance of PDGF in human decidua.

Binding Sites

Costal2, a novel kinesin-related protein in the Hedgehog signaling pathway.

The Hedgehog (HH) signaling proteins control cell fates and patterning during animal development. In Drosophila, HH protein induces the transcription of target genes encoding secondary signals such as DPP and WG proteins by opposing a repressor system. The repressors include Costal2, protein kinase A, and the HH receptor Patched. Like HH, the kinase Fused and the transcription factor Cubitus interruptus (CI) act positively upon targets. Here we show that costal2 encodes a kinesin-related protein that accumulates preferentially in cells capable of responding to HH. COS2 is cytoplasmic and binds microtubules. We find that CI associates with COS2 in a large protein complex, suggesting that COS2 directly controls the activity of CI.

Animals