Biomedical subjects

N Fukuda

Publications and source records attributed to N Fukuda.

At least 127 records · Page 7Linked to original sources

PubMed1998

Echocardiographic assessment of right atrial function in patients with myocardial infarction with reference to obstructive lesions of the coronary arteries.

We assessed the relationship between right atrial (RA) function and obstructive lesions of the coronary arteries in 29 patients with recent or old myocardial infarction (MI). Patients were divided into 3 groups according to the location of obstructions as follows: obstruction at the proximal right coronary artery (segments 1 and 2) (RCA proximal group, n=9); obstruction at the distal RCA (segments 3 and 4) (RCA distal group, n=6); and obstruction at the left anterior descending coronary artery (LCA group, n=14). The RA volume and the fractional change in the RA area during atrial contraction (RA %AC) were evaluated by apical 2-dimensional echocardiography. The right ventricular (RV) end-diastolic pressure (RVEDP) was measured in 4 patients in the RCA proximal group and 4 patients in the LCA group. The ejection fraction of the right ventricle (RVEF) was measured by radionuclide angiography or 2-dimensional echocardiography in 7 patients in the RCA proximal group, 5 patients in the RCA distal group, and 7 patients in the LCA group. The RVEF tended to be lower in the RCA proximal group than in the RCA distal and LCA groups. The RA volume was significantly greater in the RCA proximal group than in the LCA group. The RA %AC was significantly smaller in the RCA proximal group than in the RCA distal and LCA groups. There were no significant differences in the early diastolic RV inflow velocity among groups, but the late diastolic RV inflow velocity was significantly lower in the RCA proximal group than in the RCA distal and LCA groups. There was no significant difference in the RVEDP between the RCA proximal and LCA groups. Thus, RA dysfunction in the RCA proximal group appeared to be due to myocardial damage rather than to afterload mismatch. These findings suggest that RA dysfunction may occur in patients with an inferior MI who have an obstructive lesion of the proximal RCA.

Aged↗

PubMed1998

Difference in systolic motion velocity of the left ventricular posterior wall in patients with asymmetric septal hypertrophy and prior anteroseptal myocardial infarction. Evaluation by pulsed tissue Doppler imaging.

The left ventricular (LV) posterior wall in patients with asymmetric septal hypertrophy or prior anteroseptal myocardial infarction (A-MI) frequently demonstrates normal or supernormal motion to compensate for hypokinesis of the interventricular septum. This study evaluated the systolic motion velocity of the posterior wall in these conditions using a pulsed tissue Doppler imaging system. The study population consisted of 30 patients with hypertrophic cardiomyopathy (HC) and asymmetric septal hypertrophy, 25 with prior A-MI and 30 normal controls. The systolic excursion of the posterior wall was obtained by M-mode echocardiography. The endocardial motion velocities of the posterior wall were obtained by pulsed tissue Doppler imaging. The systolic excursion of the posterior wall was significantly greater in the A-MI and HC groups than in the control group, and was significantly greater in the A-MI group than in the HC group. The peak systolic velocity of the posterior wall was significantly lower in the HC group than in the control and A-MI groups, and the time from the electrocardiographic Q wave to the peak of the systolic wave of the posterior wall was significantly longer in the HC group than in the other groups. There were rough negative and positive correlations between the LV end-diastolic pressure and the peak systolic velocity and time from the Q wave to the peak of the systolic wave, respectively. In conclusion, LV myocardial contractility in HC patients was impaired when compared to A-MI patients despite similar posterior wall motion on the M-mode echocardiogram. Pulsed tissue Doppler imaging method may provide new insights and allow further evaluation of myocardial dysfunction.

Cardiac Catheterization↗

PubMed1998

Right heart flow dynamics after tricuspid valve annuloplasty. Characteristics and time course.

To evaluate the effect of tricuspid annuloplasty (TAP) on right heart flow dynamics, we analyzed tricuspid inflow velocity pattern, jugular venous pulse and color Doppler flow signal of tricuspid regurgitation (TR) before and after surgery in 16 patients who underwent TAP (TAP group). Cardiac rhythm was atrial fibrillation in all patients. Twelve patients with lone atrial fibrillation served as controls (AF group). Patients in the TAP group were studied before and serially after surgery with a mean follow-up period of 2.7 years. TAP was performed according to the modified De Vega technique in all patients. In a comparison of the most recent data in the TAP group and the data in the AF group, the maximum tricuspid inflow velocity was significantly increased, and both the deceleration time of the tricuspid inflow velocity wave and the y-h interval of the jugular venous pulse were significantly prolonged in the TAP group compared to the AF group. Immediately after surgery, in the TAP group, the area of the TR jet was markedly decreased, and the deceleration time of the tricuspid inflow velocity wave was significantly prolonged compared to those before surgery. The area of the TR jet was dramatically decreased and remained small during the follow-up period. Thus, TAP may produce mild tricuspid stenosis but may also confer sustained preventive effects against TR.

Adult↗

PubMed1998

Relationship between flow dynamics in the left atrium and hemostatic abnormalities in patients with nonvalvular atrial fibrillation.

To investigate the relationship between left atrial (LA) flow dynamics and hemostatic markers in nonvalvular atrial fibrillation (AF), 45 patients with nonvalvular AF who had not received anticoagulants were evaluated by transesophageal echocardiography. We determined the LA appendage flow and the presence of LA spontaneous echo contrast (SEC) or thrombus. We measured plasma levels of thrombin-antithrombin III complex (TAT), fibrinopeptide A, D-dimer, beta-thromboglobulin, and platelet factor 4 in peripheral blood as hemostatic markers. The patients were divided into a low-velocity group (n = 19; sum of peak emptying and filling LA appendage flow velocities < 40 cm/s) and a high-velocity group (n = 26; > or = 40 cm/s). The maximum LA diameter was significantly greater and the LA expansion fraction was significantly smaller in the low-velocity group than in the high-velocity group. LA SEC or thrombus was observed in 11 patients (58%) in the low-velocity group, but not in any patients in the high-velocity group (p < 0.001). The plasma levels of TAT, fibrinopeptide A, D-dimer, beta-thromboglobulin, and platelet factor 4 were significantly higher in the low-velocity group than in the high-velocity group. The plasma levels of TAT, fibrinopeptide A, beta-thromboglobulin, and platelet factor 4 were significantly higher in 8 patients without LA SEC or thrombus in the low-velocity group than in 26 patients in the high-velocity group. Patients with nonvalvular AF accompanied by an enlarged and dysfunctioning LA and a decreased LA appendage flow velocity had increased intravascular coagulation-fibrinolysis activity and platelet activation. These abnormalities may be closely related to the thrombogenetic state in patients with nonvalvular AF.

Adult↗

PubMed1998

Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by 123I-MIBG imaging.

To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62 +/- 11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n = 7), hypertension (n = 2), and atrial fibrillation (n = 1). Radioiodinated metaiodobenzyl guanidine (123I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, (1) left ventricular ejection fraction (LVEF) increased significantly from 38.3 +/- 6.9% to 47.5 +/- 14.7%; (2) sub-maximal exercise time increased significantly from 205 +/- 112 to 272 +/- 120 seconds; (3) the heart to mediastinum (H/M) ratio of 123I-MIBG increased significantly (early image: 1.99 +/- 0.38 versus 2.20 +/- 0.50; delayed image: 1.86 +/- 0.44 versus 2.09 +/- 0.51); and (4) the washout rate of 123I-MIBG decreased slightly from 29.1 +/- 9.1% to 25.4 +/- 7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and 123I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure.

3-Iodobenzylguanidine↗

PubMed1998

Effect of emeriamine, an inhibitor of fatty acid oxidation, on metabolic fate of a geometrical isomer of linoleic acid in perfused rat liver.

To estimate the relative significance of exogenous vs. endogenous fatty acids in increasing hepatic triacylglycerol secretion following an inhibition of fatty acid oxidation by emeriamine, livers from 2-d-fasting rats were perfused with or without an inhibitor in the presence of a geometrical isomer of linoleate (linolelaidic acid, trans,trans-9,12-octadecadienoic acid). Emeriamine added to the perfusion medium at 2 h of the recirculating perfusion period caused immediate and complete cessation of ketone body production while it increased triacylglycerol and cholesterol secretion by the liver without affecting uptake of exogenous linolelaidic acid. The increase in the triacylglycerol secretion by emeriamine was accompanied by a marked increase in the proportion of linolelaidic acid in this lipid molecule in the perfusate and in the liver. The calculated amounts of exogenous linolelaidate, compared with those of endogenous fatty acids in the secretory triacylglycerol, suggested that the former compared with the latter contributes more to the drug-mediated increase in triacylglycerol secretion. This drug caused a marked reduction of mitochondrial carnitine palmitoyltransferase activity in perfused liver. These results suggest that a blockade of fatty acid oxidation by emeriamine, through an inhibition of carnitine palmitoyltransferase, diverts predominantly the exogenous free fatty acids from oxidation to the esterification pathway and subsequently stimulates the synthesis and secretion of triacylglycerol-rich lipoproteins.

3-Hydroxybutyric Acid↗

PubMed1998

Reciprocal effects of dietary sesamin on ketogenesis and triacylglycerol secretion by the rat liver.

The effects of dietary sesamin (a mixture of sesamin and episesamin, 1:1, w/w) on ketone body production and lipid secretion were studied in isolated perfused liver from rats given sesamin. Feeding sesamin at the dietary level of 0.2% from 14 to 16 d resulted in an enlargement of liver weight. Ketone body production was significantly elevated in the livers perfused with oleic acid in comparison with those perfused without an exogenous-free fatty acid, and sesamin feeding caused a stimulation of ketone body production, especially when exogenous oleic acid was provided. On the other hand, the ratio of beta-hydroxybutyrate to acetoacetate, an index of mitochondrial redox potential, tended to increase in the livers perfused with oleic acid compared with those without fatty acid, thought it was consistently lowered by dietary sesamin. The cumulative secretion of triacylglycerol, but not of cholesterol, by the livers from sesamin-fed rats was decreased markedly, especially when exogenous oleic acid was provided, suggesting an inverse relationship between the rates of ketogenesis and triacylglycerol secretion. These results suggest that dietary sesamin exerts its hypotriglyceridemic effect at least in part through an enhanced metabolism of exogenous-free fatty acid to oxidation at the expense of esterification in rat liver.

3-Hydroxybutyric Acid↗

PubMed1998

[Evaluation of cardiac function by various cardiac imaging techniques in mitochondrial cardiomyopathy: a case report].

A 39-year-old man with cardiomyopathy due to point mutation of mitochondrial DNA(3243) was admitted to our hospital because of exertional dyspnea accompanied by hearing disturbance and diabetes mellitus. Echocardiography revealed asymmetric hypertrophy of the anterolateral and posterior walls and systolic dysfunction of the left ventricle (fractional shortening = 18%). Pulsed Doppler mitral inflow velocity wave showed a pseudonormalized pattern. Iodine-123 betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) myocardial scintigraphy showed decreased accumulation in the anterolateral, posterior, and apical walls. Left ventriculography showed moderately decreased ejection fraction (43%), and left ventricular end-diastolic pressure was mildly elevated (18 mmHg). Angiography showed normal coronary arteries, but coronary flow reserve measured by administering intravenous adenosine triphosphate was impaired in the left anterior descending and left circumflex arteries compared to the right coronary artery. Intracellular accumulations of abnormal mitochondria were detected by histologic examination of the cardiac and skeletal muscles. Evaluation of cardiac function showed that the area of myocardial hypertrophy was nearly consistent with the region of decrease in 123I-BMIPP accumulation and coronary flow reserve.

Adult↗

PubMed1998

[Effects of uvulopalatopharyngoplasty on patients with obstructive sleep apnea--the severity of preoperative tonsillar hypertrophy].

Predicting outcome following uvulopalatopharyngoplasty (UPPP) in obstructive sleep apnea is difficult. We hypothesized that UPPP is effective in obstructive sleep apnea patients with severe tonsillar hypertrophy. We examined the relationship between the severity of pre-operative tonsillar hypertrophy and the effect of UPPP in 38 patients with obstructive sleep apnea (oxygen desaturation index (ODI) > or = 20). The patients were classified into three groups according to the Mackenzie Classification of tonsillar hypertrophy. Ten patients were classified as grade 1 (M1) hypertrophy, i.e. tonsils just visible beyond the palatal arch. Five patients had grade 3 (M3) hypertrophy, i.e. tonsils appearing to contact each other at the midline. The remaining 23 patients had grade 2 (M2) hypertrophy, i.e. intermediate enlargement. We measured the apnea index, ODI, DST 90, and DST 85 (%time with SaO2 < or = 90% and < or = 85%, respectively) using a screening device for sleep apnea (Apnomonitor II, CHEST M. I. Co. Tokyo, Japan) before and after UPPP. Following UPPP, the mean ODI decreased significantly in all groups: 59 to 9/hr (p < 0.005) in the M3 group, 53 to 27/hr (p < 0.001) in the M2 group, and 48 to 33/hr (p < 0.05) in the M1 group. Post-UPPP ODI decreased by 83% in M3, 45% in M2, and 28% in M1 patients. Successful UPPP, defined by a post-UPPP ODI of less than 20/hr and a greater than 50% decrease in post-UPPP ODI, occurred in 80% of M3, 43% of M2, and 10% of M1 patients. We conclude that tonsillar hypertrophy can predict a successful response to UPPP in obstructive sleep apnea patients.

Adult↗

PubMed1998

[Cardiac amyloidosis with atrioventricular valve thickening and left atrial dysfunction: a case report].

A 70-year-old man with cardiac amyloidosis was referred to our hospital because of exertional chest pain accompanied by ischemic changes on electrocardiography on April 2, 1997. Transthoracic echocardiography revealed a normal size and normally contracted left ventricle without hypertrophy and "granular sparkling" quality of the myocardium, thickening of the mitral and tricuspid valves, and enlargement of the left atrium with reduced booster pump function. Pulsed Doppler mitral inflow velocity wave showed a pseudonormalized pattern, and pulmonary venous flow velocity wave showed a non-compliant pattern. Transesophageal echocardiography revealed thickening and reduced movement of the interatrial septum and reduced flow velocity in the left atrial appendage, suggesting left atrial dysfunction. Adenosine triphosphate (ATP) stress thallium-201 myocardial scintigraphy showed reversible patchy defect mainly in the posterolateral wall. Left ventricular end-diastolic and pulmonary capillary wedge pressures were mildly elevated. Angiography showed normal coronary arteries, but coronary flow reserve measured by administering intravenous ATP in the left anterior descending artery was severely impaired. A rectal biopsy specimen was positive by Congo red staining. Thus, angina pectoris in this patient may be due to amyloid infiltration of the small intramural coronary arteries. Atrioventricular valve thickening and left atrial dysfunction are important clues to diagnose cardiac amyloidosis.

Adenosine Triphosphate↗

PubMed1997

Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation.

Conventional assessment of left ventricular (LV) relaxation by calculating the time constant of LV pressure decay during the isovolumic diastole requires an invasive approach. Conversely, noninvasive parameters obtained by measuring isovolumic relaxation time and transmitral flow velocity often give inaccurate information. Using LV pressure curve, pulsed Doppler echocardiography, and pulsed Doppler tissue imaging in 38 patients with heart disease and 12 control subjects, we calculated the time constant and recorded transmitral flow velocity and motion velocities at the endocardial portions of the ventricular septum and LV posterior wall. Compared with the controls, patients exhibited a prolonged time constant, a decreased peak early diastolic velocity of the LV posterior wall, and a prolonged time interval from the second heart sound to the peak of the early diastolic wave. The time constant correlated well with the isovolumic relaxation time and various parameters calculated from the transmitral flow velocity, except in patients with elevated LV end-diastolic pressure. In all subjects, the time constant correlated negatively with the peak early diastolic velocity of the posterior wall and positively with the time from the second heart sound to the peak of the early diastolic wave. Thus, early diastolic parameters derived from the motion velocity of the LV posterior wall by pulsed Doppler tissue imaging were closely related to the time constant. This technique may allow noninvasive evaluation of abnormal LV relaxation in patients with various heart diseases.

Blood Flow Velocity↗

PubMed1997

Evaluation of left atrial appendage function by measurement of changes in flow velocity patterns after electrical cardioversion in patients with isolated atrial fibrillation.

We investigated temporary changes in left atrial appendage (LAA) flow velocity patterns in patients undergoing electrical cardioversion for chronic isolated atrial fibrillation, and evaluated the role of active LAA contraction in directing blood flow to the left atrial main chamber and left ventricle. The study consisted of 26 patients with chronic isolated atrial fibrillation treated with electrical cardioversion and 20 normal controls in sinus rhythm. Using transthoracic and transesophageal Doppler echocardiography, we recorded transmitral, pulmonary venous, and LAA flow velocity patterns before, 24 hours, and 1 week after cardioversion in all subjects. In the 15 patients who underwent successful cardioversion, the maximal LAA area 24 hours after cardioversion was smaller than the area before cardioversion, whereas LAA ejection fraction during atrial systole and peak atrial systolic emptying velocity of the LAA flow were lower 24 hours after cardioversion than those in the control group. One week after cardioversion, maximal LAA area and LAA peak atrial systolic emptying velocity were restored to levels approximately equivalent to those in the control group, although LAA ejection fraction was lower than in the control group. Maximal LAA area and LAA peak atrial systolic emptying velocity correlated negatively and positively with LAA ejection fraction, respectively, 24 hours and 1 week after cardioversion. These results suggest that LAA and the left atrial main chamber show stunning 24 hours after cardioversion, and the atrial systolic emptying wave of LAA flow is generated by active LAA contraction.

Adult↗

PubMed1997

Transesophageal pulsed Doppler echocardiographic evaluation of left atrial systolic performance in hypertrophic cardiomyopathy: combined analysis of transmitral and pulmonary venous flow velocities.

BACKGROUND: Hypertrophic cardiomyopathy (HC) is characterized by impaired left ventricular (LV) diastolic function due to an increase in LV wall thickness. The severity of this disease varies depending on the localization and extent of the hypertrophied myocardium and the presence and extent of myocardial disarray or fibrosis. HYPOTHESIS: The purpose of this study was to examine the background of hemodynamic abnormalities between the left atrium and the left ventricle during atrial systole in patients with HC using pulsed Doppler echocardiography. METHODS: Hemodynamic abnormalities between the left atrium and left ventricle during atrial systole were evaluated in patients with HC using transmitral flow (TMF) and pulmonary venous flow (PVF) velocities obtained by transesophageal pulsed Doppler echocardiography. The study population included 50 patients with HC, including 39 with asymmetric septal hypertrophy and 11 with apical hypertrophy, and showing fractional shortening of the left ventricle > or = 30%. They were classified into three groups: (1) Group A (n = 11): the ratio of the late to early TMF velocity < 1, and peak atrial systolic PVF velocity (PVA) < 25 mm/s; (2) Group B (n = 13): their ratio < 1, and PVA > or = 25 mm/s; and (3) Group C (n = 26): their ratio > or = 1. The mean age of patients in Group A was lower than that in Groups B and C. RESULTS: Left atrial dimension in Group B was significantly greater than that in the other HC groups and the control group. Furthermore, left atrial volume changes during atrial systole in Group B were significantly smaller than those in the other HC groups and the control group. Peak atrial systolic PVF velocity in Group B was significantly higher than that in the control group and in Group C. The duration of the atrial systolic waves of the TMF and PVF in Group B was significantly shorter and longer, respectively, than that in Group A. Left ventricular end-diastolic pressure (LVEDP) decreased in descending order with Group B > Group C > Group A. In all patients there was a significant positive correlation between the LVEDP and peak atrial systolic PVF velocity or the difference in duration between the atrial systolic waves of PVF and TMF. Plots of these values shifted toward the left and inferiorly in Group A, and toward the right and superiorly in Group B. CONCLUSION: Peak velocity and duration of TMF and PVF during atrial systole by transesophageal pulsed Doppler echocardiography are useful indices of hemodynamic abnormalities between the left atrium and the left ventricle during atrial systole, particularly a forceful atrial contraction mismatched to the left atrial afterload and severity of LV diastolic dysfunction, in HC.

Adult↗

PubMed1997

Effect of dibutyryl cyclic AMP on plasma renin activity in normal men and patients with primary aldosteronism.

Dibutyryl cyclic AMP (DBcAMP) directly stimulates the release of renin from the juxtaglomerular (JG) cells in vitro. We investigated the effect of DBcAMP on plasma renin activity (PRA) in 6 normal men and in 8 patients with primary aldosteronism (PA). A 20-min infusion of 0.33 mg/kg/min of DBcAMP significantly increased PRA in normal men, but had little effect on PRA in patients with PA. Infusion of DBcAMP significantly reduced the blood pressure and the levels of serum sodium and potassium in normal men and the patients with PA. Infusion of DBcAMP significantly increased urine volume in normal men, but not in patients with PA. Urinary excretion of sodium increased in both groups after the infusion of DBcAMP. Thus, DBcAMP did not stimulate renin release in patients with PA, suggesting that the chronic excess production of aldosterone suppresses the release of renin from JG cells.

Adult↗

PubMed1997

Role of long-form PDGF A-chain in the growth of vascular smooth muscle cells from spontaneously hypertensive rats.

Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit exaggerated growth relative to cells from normotensive Wistar-Kyoto (WKY) rats. Platelet-derived growth factor (PDGF) A-chain has been implicated in the exaggerated growth of VSMC from SHR. Two isoforms of PDGF A-chain mRNA that either include (long form) or exclude (short form) exon 6 are produced as a result of alternative splicing. The expression of the long-form PDGF A-chain at the mRNA level and its role in the growth of VSMC from SHR have now been investigated with the use of an antisense oligodeoxynucleotide (ODN) complementary to exon 6 of the PDGF A-chain gene. Reverse transcription-polymerase chain reaction (RT-PCR) analysis with primers encompassing exon 6 of PDGF A-chain mRNA revealed bands corresponding to both long- and short-form PDGF A-chain transcripts in quiescent VSMC from both SHR and WKY rats, with the long-form mRNA more abundant in VSMC from SHR than in cells from WKY rats. Expression of the long-form of PDGF A-chain mRNA was enhanced with angiotensin II and transforming growth factor-beta1 in VSMC from SHR, but not in cells from WKY rats. The antisense ODN significantly inhibited DNA synthesis by VSMC from SHR, but not by cells from WKY rats, in the absence or presence of serum. In addition, the antisense ODN significantly inhibited serum induced proliferation of VSMC from SHR, but not those from WKY rats. The antisense ODN abolished expression of the long-form PDGF A-chain mRNA in VSMC, suggesting that its inhibitory effects on the growth of VSMC from SHR are mediated by depletion of the long-form transcripts. These results indicate that the long-form of PDGF A-chain contributes to the exaggerated growth of VSMC from SHR.

Animals↗

PubMed1997

Sequences of exon 6 and the adjacent intron boundaries of the rat platelet-derived growth factor A-chain gene: implications for alternative splicing.

Platelet-derived growth factor (PDGF) is a potent stimulator of vascular smooth muscle cell growth. Two isoforms of PDGF A-chain mRNA that either include (long form) or exclude (short form) exon 6 are produced as a result of alternative splicing in mouse, rabbit, and human. The short form of PDGF A-chain is expressed in both resting and activated cells, while the long form is present predominantly in activated cells. Reverse transcription-polymerase chain reaction analysis with primers encompassing exon 6 revealed the presence of both long- and short-form PDGF A-chain transcripts in rat vascular smooth muscle cells. The nucleotide sequences of exon 6 and its intron boundaries were determined from rat vascular smooth muscle cell cDNA and rat leukocyte genomic DNA. Translation of the long form of PDGF A-chain mRNA was shown to terminate in the 70-base pair exon 6. Conserved sequences that may contribute to the regulation of alternative RNA splicing were identified in intron 5.

Alternative Splicing↗

PubMed1997

Studies on neurosteroids. V: Separation and characterization of pregnenolone 3-stearate in rat brains using high-performance liquid chromatography.

The separation and characterization of pregnenolone 3-stearate in rat brains are carried out using high-performance liquid chromatography (HPLC). The pregnenolone 3-stearate is obtained from a whole rat brain by extraction with ethyl acetate followed by silica gel column chromatography. The obtained fraction is derivatized with 1-dimethylaminonaphthalene-5-sulfonylhydrazine (dansylhydrazine) or 4-(N,N-dimethylaminosulfonyl)-7-hydrazino- 2,1,3-benzoxadiazole, and the derivative is separated by successive preparative HPLC with fluorescence detection. The chromatographic behaviors of both derivatives are identical to those of authentic samples. The former derivative obtained from the rat brain shows satisfactory mass spectral data, and after hydrolysis, dansylpregnenolone is confirmed by HPLC.

Animals↗

PubMed1997

Antisense oligodeoxynucleotide complementary to platelet-derived growth factor A-chain messenger RNA inhibits the arterial proliferation in spontaneously hypertensive rats without altering their blood pressures.

OBJECTIVE: To evaluate the effects of the antisense oligodeoxynucleotide (ODN) to platelet-derived growth factor (PDGF) A-chain messenger RNA (mRNA) on the growth of cardiovascular organs in hypertension. DESIGN: 15-Mer antisense ODN complementary to the initiation codon region of rat PDGF-A chain mRNA and non-sense ODN of identical proportion but with a random order of bases relative to that of antisense ODN were synthesized with a DNA synthesizer. METHODS: We examined the effects of the antisense ODN on the growth of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats, and on the expression of PDGF A-chain mRNA by reverse transcription and polymerase chain reaction and PDGF A-chain protein by Western blot analysis in vitro. We evaluated the distribution of 32P-labeled antisense ODN and examined the effects of the antisense ODN on the growth of cardiovascular organs in vivo. RESULTS: The antisense ODN reduced the basal DNA synthesis of VSMC from SHR significantly, but did not do so in cells from Wistar-Kyoto rats. Mutations in the antisense ODN sequence reduced the ODN-induced inhibition of DNA synthesis. Addition of serum or transforming growth factor-beta 1 increased the DNA synthesis in the SHR-derived VSMC that was inhibited by the antisense ODN. The antisense ODN inhibited the production of PDGF A-chain protein, but not of the PDGF A-chain mRNA. The injection of 32P-antisense ODN in vivo led to a greater accumulation of radioactivity in the aorta than in other organs. Infusion of antisense ODN for 28 days did not alter the systolic blood pressure appreciably in rats of either strain. However, in SHR, it reduced markedly the elevated DNA content, [3H]-thymidine uptake, and incorporation of [3H]-thymidine into aortic DNA, and suppressed the production of aortic PDGF A-chain protein. These results indicated that the PDGF A-chain is involved in the exaggerated growth of VSMC from SHR by which inhibition of the translation of PDGF A-chain mRNA to the protein with antisense ODN occurs in vitro, and that antisense ODN to PDGF A-chain suppresses the exaggerated arterial proliferation in SHR without altering the high blood pressure in vivo. CONCLUSION: These results imply that inhibition of the final responsible growth factor PDGF A-chain by antisense ODN can suppress the arterial proliferation in hypertension without altering the blood pressure, suggesting that the arterial proliferation in hypertension is independent of the high blood pressure in part, and that antisense therapy could be feasible for treating hypertension.

Animals↗