Differing effects of liraglutide on gastric emptying in Japanese patients with type 2 diabetes.

This study was performed to clarify the influence of liraglutide on gastric emptying in Japanese patients with type 2 diabetes. In 16 patients, the [(13) C]-acetate breath test was performed to compare gastric emptying before and after liraglutide treatment. We found two patterns of response, with gastric emptying being delayed by liraglutide in seven patients (delayers) and not delayed in nine patients (non-delayers). The mean increase of the maximum gastric emptying time was 31 ± 4 min (p < 0.01 vs. baseline) in the delayers, while it was only 2 ± 3 min (p = 0.60 vs. baseline) in the non-delayers. The delayers showed a greater early decrease of AUC-PG from 0 to 60 min, despite no increase of the plasma insulin level compared with non-delayers. In conclusion, the effect of liraglutide treatment on gastric emptying shows heterogeneity, and patients can be classified as delayers or non-delayers.

Presence of particular transcription regulatory elements in the 5'-intergenic region shared by the chicken H2A-III and H2B-V pair.

The two chicken histone gene families, H2A and H2B, contain nine and eight members, respectively, within two major histone gene clusters. Six genes each from families H2A and H2B have been found to be closely associated in inverted directions as H2A/H2B gene pairs. Two previously sequenced H2A members (H2A-I and H2A-II) encode the same amino acid (aa) sequence (class I), whereas seven sequenced H2B genes encode three different variants (classes I, II and III). In this study, we first sequenced H2A-III, a member of the H2A family, which is located in inverted orientation and 350 bp upstream from H2B-V, encoding the class-III H2B protein. The protein encoded by H2A-III differs from the class-I H2A protein in a single aa (Ala70-->Pro; class II). As a step toward elucidation of the transcriptional regulation of the H2A and H2B families, we fused this 5'-intergenic region to the cat gene in inverted orientations to generate two chimeric plasmids, pH2A-III-350 and pH2B-V-350. Transient CAT assays using these constructs indicated that the promoter of H2B-V is more active than that of H2A-III. CAT assays with 5'-deletion mutants of H2A-III and H2B-V showed that they each possess particular transcriptional motifs which are located relatively close to, or apart from, their own coding regions. These findings, together with those reported previously on the H2A-V/H2B-II pair, suggest distinct manners of transcription regulation of different members of the chicken histone gene families, H2A and H2B.

Nucleotide sequences of two members of the chicken H4 histone-encoding gene family.

The nucleotide sequences of two genes (H4-III and H4-IV) from the chicken H4 histone-encoding gene family have been determined. The four H4 genes, including the previously sequenced H4-I and H4-II genes, encode the same amino acid sequence and possess several copies of the possible Sp1-binding sequences on the coding and noncoding strands within the 5'-flanking regions.

Prostaglandin dehydrogenase activity in placenta and in maternal lung, kidney, and gastric mucosa during rat pregnancy.

The purpose of this study was to investigate the changes in prostaglandin dehydrogenase (PGDH) activity in various organs of the rat during pregnancy. PGDH activity was evaluated in lung, kidney, and gastric mucosa of male and nonpregnant female rats, and in these tissues as well as in placenta of pregnant rats at various stages of gestation. The specific activity of PGDH in placenta decreased until day 15 of pregnancy; thereafter, the specific activity of PGDH increased, reaching maximal levels at term. The specific activity of PGDH in lung and kidney tissue of pregnant rats was greater than that in the same tissues of nonpregnant rats; in these tissues the specific activity increased from early pregnancy through day 21 of pregnancy but was decreased significantly on day 22. The specific activity of PGDH in kidney of male rats was significantly greater (10 times) than that in kidney of female rats. This sex-related difference in renal PGDH activity was not found in lung and gastric mucosa. In gastric mucosa, the specific activity of PGDH on day 10 of pregnancy was significantly lower than that in gastric mucosa of nonpregnant rats. A rapid decrease in the specific activity at term was a phenomenon common to lung, kidney, and gastric mucosa, and was distinctly different from the marked increase in the activity in placenta at term. Thus, in this study, we present evidence that the activity of PGDH is modulated in a tissue-specific manner during pregnancy. We speculate that PGDH in maternal, fetal, and placental tissues serves a role in the maintenance of pregnancy and in growth and development of the fetus by regulating the tissue levels of bioactive prostaglandins.

[Left ventricular relaxation property evaluated by isovolumic relaxation flow].

The blood flow recorded in the center of the left ventricle (LV) during the isovolumic relaxation period, i.e., isovolumic relaxation flow (IRF), was evaluated by pulsed Doppler echocardiography. The subjects consisted of 17 normal persons, 12 patients with angina pectoris (AP), 63 with old myocardial infarction (OMI), 16 with hypertrophic cardiomyopathy (HCM) and 16 with dilated cardiomyopathy (DCM). In the normal subjects, the IRF showed a laminar flow and it was directed from the center of the LV toward the apex. The maximum velocity of the IRF coincided with the second heart sound. In the patients with heart diseases, the IRF was classified into three patterns. Type A, in which the IRF was directed toward the apex of the LV: This pattern was observed in two different patient groups from the standpoint of LV wall motion and LV ejection fraction (LVEF). One group had either a normal LVEF without wall motion abnormalities or normal LVEF with a small area of abnormal wall motion in the anterior and/or apical portions. The other group had various LVEF with abnormalities of wall motion in the posterior and/or inferior portions. The duration of the IRF in type A was prolonged in AP (142 +/- 35 msec), OMI (152 +/- 14 msec), HCM (166 +/- 33 msec) and DCM (171 msec) when compared with those of the normal subjects (119 +/- 35 msec). The acceleration time (time interval from the beginning of the IRF to the point of the maximum flow velocity) in the normal subjects was 25 +/- 8 msec, but they were prolonged in AP (37 +/- 12 msec), OMI (59 +/- 22 msec), HCM (64 +/- 18 msec) and DCM (58 msec). The acceleration rate (increment of the flow velocities per sec) was significantly decreased in AP (8.9 +/- 3.2 m/sec2), OMI (4.5 +/- 2.7 m/sec2), HCM (4.5 +/- 1.1 m/sec2) and DCM (3.7 m/sec2) when compared with those of the normal subjects (12.6 +/- 4.0 m/sec2). Type B, in which the IRF was directed away from the LV center to the base of the LV: The patients with this type had slightly depressed LVEF with moderately extended abnormalities of wall motion in the anterior and/or apical portions. Type C without discernible IRF: The patients with this type had severely depressed LVEF with generalized abnormalities of wall motion. It was concluded that the patterns of the IRF are affected by regional wall motion and the IRF seems to be caused by LV relaxation.

[Quantitation of mitral regurgitation by left ventricular blood flow dynamics: a pulsed Doppler echocardiographic study].

Using pulsed Doppler echocardiography, the blood flow dynamics in the left ventricular cavity were studied in 52 cases with mitral regurgitation (MR) (32 cases of grade 1 or 2 and 20 cases of grade 3 or 4 according to the Sellers' classification) were studied to quantify the severity of MR. Twelve healthy subjects served as the control. The results were as follows: At the mitral orifice, systolic laminar flow toward the left atrial cavity was observed in 17 cases with grade 3 or 4 MR. This flow was shown to begin at the isovolumic contraction phase and it had a higher velocity in end-systole. Thus, it could easily be differentiated from ejection flow observed in the left ventricular outflow tract. The duration of systolic blood flow in the mid-ventricle was significantly prolonged over that in the outflow tract in cases with grade 3 or 4 MR compared to those with grade 1 or 2 MR (grade 1 or 2: 4 +/- 27 msec, grade 3 or 4: 65 +/- 35 msec, p less than 0.001), indicating that MR continued even after the end of left ventricular ejection. The velocity of early diastolic left ventricular inflow was estimated for cases having isolated MR (16 cases with mitral chordal rupture and one case of mitral valve prolapse syndrome). In the healthy subjects and cases with grade 1 or 2 MR, the velocity was less than 84 cm/sec. The velocity was increased more than 100 cm/sec in grade 3 or 4 MR. These observations indicated the clinical potential of abnormal blood flow dynamics in the left ventricular cavity in the semi-quantification of MR.

Clinical significance of the right ventricular free wall appearance on stress Tl-201 myocardial images in ischemic heart disease.

In order to evaluate the clinical significance of thallium (Tl)-201 myocardial imaging for diagnosing the right ventricular (RV) ischemia, we studied the relationship of right ventricular free wall (RVFW) appearance on myocardial images to coronary arteriographic findings. Patients were divided into 3 groups as follows: 1) normal control (NC) group (19 cases) without angiographically documented coronary artery disease; 2) non-RCA group (18 cases) with significant coronary artery lesion restricted to the left coronary artery (LCA); and 3) RCA group (36 cases) with significant right coronary artery (RCA) stenosis regardless of underlying LCA disease. After the patients had exercised up to 80-85% of the predicted maximal heart rate, immediate and 3-4 hour delayed myocardial images were obtained. As for presence or absence of the RV ischemia on images, the RVFW appearance in 30 degrees and 60 degrees left anterior oblique (LAO) views were assessed carefully. On the immediate images, all patients except one in the NC group and all except 3 in the non-RCA group demonstrated 'continuous visualization' of the RVFW in both views. In the RCA group, 6 showed 'non-visualization' and 11 'defective visualization' of the RVFW in 30 degrees LAO view. In 60 degrees LAO view, 6 presented 'non-visualization' and other 6 'defective visualization' of the RVFW. On the delayed images, although none of the patients in the groups NC and non-RCA demonstrated redistribution phenomenon of the RVFW, 4 patients in the RCA group showed redistribution of Tl-201 into the RVFW. Non- and defective visualization of the RVFW on the immediate images were related to the proximally located RCA lesion, previous history of inferior myocardial infarction and high grade RCA stenosis. Collateral vessels seemed to protect the RVFW against the development of exercise induced ischemia and affect the occurrence of redistribution of Tl-201 into the RVFW. In conclusion, stress Tl-201 myocardial imaging enables us to estimate the myocardial blood flow of the RV and is a useful non-invasive method in the evaluation of RV ischemia.

[Clinical significance of stress thallium-201 myocardial scintigraphy for evaluation of right ventricular ischemia].

Although stress thallium (T1)-201 myocardial imaging has been used for evaluation of the ischemic lesion of the left ventricle, there are few reports on the usefulness of this method for the assessment of the right ventricle in ischemic heart disease. The patients (pts) fell into three distinct groups according to the findings of the coronary arteriogram: normal control group (16 cases) without angiographically documented coronary artery disease; non-RCA group (16 cases) with a significant stenosis (greater than or equal to 75% narrowing) in the left coronary artery but free of a significant right coronary artery (RCA) stenosis; RCA group (28 cases) with a significant RCA stenosis regardless of the presence or absence of a significant left coronary artery lesion. After the pts were exercised to 80-85% of the expected maximum heart rate, immediate and delayed (3 to 4 hrs) T1-201 myocardial images were obtained. The images of the right ventricular free wall ( RVFW ) in 30 degrees and 60 degrees left anterior oblique (LAO) projections were evaluated visually with regard to the presence or absence of a defective T1-201 uptake, degree of the radioactivity and redistribution phenomenon of the RVFW . On immediate images, all normal controls and 13 pts in non-RCA group had continuous visualization of the RVFW . In RCA group, the RVFW was not visualized in five and 11 showed defective visualization of the RVFW in the 30 degrees LAO projection. In 60 degrees LAO projection, the RVFW was not visualized in six and five had defective visualization. On delayed images in RCA group, two pts who had no inferior myocardial infarction (MI) had redistribution of T1-201 into the RVFW . Defective visualization of the RVFW on the image was associated with location of the RCA lesion, history of inferior MI and degree of RCA stenosis. Collateral circulation seemed to protect the RVFW against the development of exercise-induced ischemia and affect the occurrence of redistribution of T1-201 into the RVFW . The RVFW findings on images improved the sensitivity for identifying the pts with RCA disease, compared with the LV findings alone. Thus, stress T1-201 myocardial imaging is able to visualize the myocardial blood flow of the RVFW and may provide a useful non-invasive method in the evaluation of right ventricular ischemia.

A thrombotic tendency in patients with infective endocarditis.

An attempt was made to evaluate a thrombotic tendency in cases of infective endocarditis (IE) from the viewpoint of the changes of platelets and coagulo-fibrinolysis. Qualitative changes of platelets by thrombi formation were detected by showing activated responses of platelets to adenosine diphosphate or collagen and by showing a high level of plasma beta-thromboglobulin which is released by platelets during aggregation. A mild hypercoagulable state without acceleration of fibrinolysis was also detected by showing low levels of plasma antithrombin III which is the most potent antithrombin in the blood and normal levels of plasma alpha 2-plasmin inhibitor in the blood. From above findings, it was concluded that a thrombotic tendency in cases of IE was clearly detected by qualitative changes of platelets by thrombi formation and by mild hypercoagulability without acceleration of fibrinolysis.

Hypercoagulability in patients with mitral stenosis -- from the viewpoint of the behavior of plasma antithrombin III and alpha2-plasmin inhibitor.

The concentration of plasma antithrombin III (AT III) and the biological activity of plasma alpha2-plasmin inhibitor (alpha 2-PI) were measured in cases of mitral stenosis (MS) and rheumatic heart disease (RHD) without MS. Cases of MS showed the findings of the low levels of plasma AT III and normal or a little higher levels of plasma alpha 2-PI, that was not recognized in RHD without MS. This finding was interpreted to be hypercoagulable because of the acceleration of coagulation and of little or slight retardation of fibrinolysis. Besides, the influence of atrial fibrillation and chronic congestive heart failure on hypercoagulability in cases of MS was detected clearly, but the influence of them in cases of non-RHD was obscure. As the results, the severer the degree of MS, the clearer the hypercoagulable state. Therefore, the prethrombotic state existed in cases of MS, combined with blood flow disturbance due to atrial fibrillation or chronic congestive heart failure, endocardial damage resulted from rheumatic fever in an early stage and hypercoagulable state mentioned above in the present study. There was no significant difference between cases with and without thrombi in the degree of hypercoagulability in subjects with MS shown in the present work. It was concluded that the consumption of AT III caused the low levels of it in cases of MS, and that the low production of AT III in the liver rather than consumption caused the low levels of it in cases of non-RHD.