No relationship between enzyme activity and structure of nucleotide binding site in sarcoplasmic reticulum Ca(2+)-ATPase from short-term stimulated rat muscle.

AIM: We examined whether structural alterations to the adenine nucleotide binding site (ANBS) within sarcoplasmic (endo) reticulum Ca(2+)-ATPase (SERCA) would account for contraction-induced changes in the catalytic activity of the enzyme as assessed in vitro. METHODS: Repetitive contractions were induced in rat gastrocnemius by electrical nerve stimulation. Measurements of sarcoplasmic reticulum properties were performed on control and stimulated muscles immediately after or at 30 min after the cessation of 5-min stimulation. In order to examine the properties at the ANBS, the binding capacity of SERCA to fluorescence isothiocyanate (FITC), a competitive inhibitor at the ANBS, was analysed in microsomes. RESULTS: Short-term electrical stimulation evoked a 23.9% and 32.6% decrease (P < 0.05) in SERCA activity and in the FITC binding capacity, respectively, in the superficial region of the muscle. Whereas SERCA activity reverted to normal levels during 30-min recovery, a restoration of the FITC binding capacity did not occur. CONCLUSION: The discordant changes between the enzyme activity and the FITC binding suggest that, at least during recovery after exercise, changes in SERCA activity may not correlate closely with structural alterations to the ANBS within the enzyme.

Synthesis and pharmacological evaluation of carboxamide derivatives as selective serotoninergic 5-HT(4) receptor agonists.

A number of new carboxamide derivatives were synthesized. The affinity of these compounds for the serotoninergic 5-HT(4) receptor was evaluated by use of radioligand-binding techniques. The agonistic activity was evaluated as the contractile effect of the ascending colon isolated from guinea-pigs. Among these compounds, 4-amino-5-chloro-2-methoxy-N-[1-[2-[(methylsulfonyl)amino]ethly]-4-piperidinylmethyl]benzamide (24) showed a high affinity for the 5-HT(4) receptor (Ki = 9.6 nM). Compound 24 displayed a higher affinity for 5-HT(4) receptors than the other receptors, including, 5-HT(3) and dopamine D(2) receptors. In addition, compound 24 was confirmed to be a potent 5-HT(4) receptor agonist (ED(50) = 7.0 nM). An interaction model between compound 24 and 5-HT(4) receptor was proposed.

Biomechanical testing of the lumbosacral spine.

OBJECTIVE: To assess various forms of anterior and posterior sacral fixation and to study the influence of anterior lumbosacral fixation and posterior pedicle fixation at L5 in conjunction with lumbosacral fixation. SUMMARY OF BACKGROUND DATA: Moments at the lumbosacral junction are high in the long constructs requiring lumbosacral fixation. The purpose of this study was to assess bending moments in flexion-extension and lateral bending and rotational forces at the lumbosacral junction involving a variety of long constructs to the lumbosacral junction. The incidence of pseudarthrosis in such constructs in the adult spine literature ranges from 7% to 40%. METHODS: An alignment jig was designed to display three-dimensional motion in the three orthogonal planes. Nine constructs of five specimens each were tested. These consisted of fixation at T12-L5-S1 (construct 1), T12-L5-S1 with anterior L5-S1 fixation and grafting (construct 2), T12-L5-S1, S2 with and without L5-S1 fixation and grafting anterior (constructs 3 and 4, respectfully), T12-S1, S2 with and without L5-S1 anterior grafting and fixation (constructs 5 and 6, respectfully), T12 Jackson intrasacral fixation with or without L5-S1 grafting anteriorly at the anterior fixation (constructs 7 and 8, respectfully), and T12-L5-S1, S2 fixation with anterior grafting only (construct 9). RESULTS: The use of anterior fixation statistically increased stiffness in extension. There was a trend toward increasing stiffness in constructs with anterior fixation (two anterior anterior-oblique L5-S1 screws) and in other loading modes as well. Failure to use L5 screw fixation significantly decreased torsional rigidity in long constructs without anterior fixation. CONCLUSIONS: In long constructs, particularly in scoliosis surgery requiring lumbosacral fixation, the addition of anterior fixation at L5-S1 is recommended. The addition of L5 fixation in addition to sacral fixation significantly decreases rotational stresses and is recommended as well.

Benzoxazines. II. Synthesis, conformational analysis, and structure--activity relationships of 3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide derivatives as potent and long-acting serotonin-3 (5-HT3) receptor antagonists.

A series of 3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide derivatives was synthesized and evaluated for serotonin-3 (5HT3) receptor antagonistic activities by means of assays of 5-HT3 receptor binding and the ability to antagonize the von Bezold-Jarisch reflex in rats. Replacement of the 1,4-benzoxazine ring with a 1,4-benzthiepine ring or seven-membered ring (i.e., 1,5-benzoxepine or 1,5-benzthiepine) resulted in decreased affinity for 5-HT3 receptor. Introduction of substituents at the 2 position of the 1,4-benzoxazine ring increased the antagonistic activities (dimethyl > methyl > dihydro > phenyl). The compounds bearing a 9-methyl-9-azabicyclo[3.3.1]non-3-yl moiety as the basic part of 3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide derivatives were equipotent to those bearing 1-azabicyclo[2.2.2]oct-3-yl moiety. The 9-methyl-9-azabicyclo[3.3.1]non-3-yl moiety was confirmed to adopt a boat-chair conformation on the basis of both NMR studies and X-ray analysis. In this series, endo-6-chloro-3,4-dihydro-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2,2, 4-trimethyl-2H-1,4-benzoxazine-8-carboxamide showed the highest affinity for 5-HT3 receptors (Ki = 0.019 nM), and a long-lasting 5-HT3 receptor antagonistic activity as evidenced by antagonism to the von Bezold--Jarisch reflex in rats. Such a long-lasting 5-HT3 receptor antagonism would be attributed to the introduction of both two methyl groups at the 2 position of the benzoxazine ring and the 9-methyl-9-azabicyclo[3.3.1]non-3-yl moiety, which adopts the boat-chair conformation.

Marine natural products. XXXIII. Theonellapeptolide IId, a new tridecapeptide lactone from the Okinawan marine sponge Theonella swinhoei.

Following the characterization of theonellapeptolides Ia-Ie (2-6), another new tridecapeptide lactone named theonellapeptolide IId (1) was isolated from the Okinawan marine sponge Theonella swinhoei. The structure of 1 has been determined on the bases of chemical and physicochemical examinations which included an HPLC-CD combined analysis of the amino acid composition. Theonellapeptolide IId (1) prevented fertilization of the sea urchin Hemicentrotus pulcherrimus at the concentration of 25 micrograms/ml or greater but did not affect early embryonic development of fertilized eggs up to the gastrula stage.

Immunohistochemical studies on the class and the subclass of the anticolon antibody and the distribution of the antigen recognized by the anticolon antibody in patients with ulcerative colitis.

The immunologic mechanisms mediated by anticolon antibodies have been suggested for the injury of colonic mucosa in ulcerative colitis (UC). For the understanding of pathogenetic relevance of the anticolon antibody in UC, we examined the class and the subclass of the anticolon antibody reactive to rat colonic epithelial cells in sera from 10 patients with UC immunohistochemically by an indirect immunoperoxidase method. We also examined the distribution of the antigen recognized by the anticolon antibody by immunoelectron microscopy. The antibody reactive to the rat colonic epithelial cell was detected in 2 of the 10 patients, and the class and subclass of the antibody was mainly IgG2. The antigen recognized by the anticolon antibody was located on the apical membrane of the colonic epithelial cells and mucous substances of the goblet cells. These findings suggest that the anticolon antibody detected in this study is inadequate to cause the colonic mucosal injury by activating complements or mediating antibody-dependent cellular cytotoxicity. A potential pathogenetic role of the anticolon antibody in UC remains to be established.

[Electrocardiographic observations of pure septal infarction: a case report].

We report a very rare case of pure septal infarction, which was closely examined with detailed electrocardiography (ECG). The patient is a 65-year-old man, who underwent percutaneous transluminal coronary angioplasty (PTCA) for exercise-induced angina. During PTCA for the target lesions in the left anterior descending artery (LAD) and diagonal branch, a large septal branch originating from the LAD was accidentally and completely occluded. Septal Q waves then disappeared from leads I, V5 and V6, and ST segments were elevated in leads V1 to V3, with concomitant ST depressions in leads I, II, aVF, V5 and V6. It was speculated that the initial electrical potential derived from the central septum may have been lost due to septal infarction, resulting in the disappearance of the septal Q waves. The present case disclosed the role of the interventricular septum in the genesis of septal Q waves in the left precordial leads.

[Right ventricular infarction/ischemia with precordial ST elevation: comparison with left ventricular anterior wall infarction].

Acute right ventricular (RV) infarction is sometimes accompanied by precordial ST elevation which is also suggestive of left ventricular (LV) anterior wall infarction. We compared 12-lead electrocardiograms between 2 groups of patients with initial acute myocardial infarction presenting precordial ST elevation, one with RV infarction (n = 11) and the other with LV anterior wall infarction (n = 42). The magnitude and extent of the ST elevation and the positions presenting the maximal ST elevation in the precordial leads differed between the 2 groups. In the inferior and lateral leads, the analysis of the ST segment shift aided in distinguishing between the 2 groups. The specific patterns of intraventricular conduction delay and frontal QRS-axis deviation were also useful for the differentiation. The best electrocardiographic variable for identifying RV infarction was inferior lead ST elevation, followed by maximal precordial ST elevation in lead V1, ST elevation limited to only one precordial lead and a cove-shaped pattern of RV conduction delay. The best electrocardiographic predictor for diagnosing LV anterior wall infarction was an isoelectric or depressed ST-segment in the inferior leads, followed by precordial ST elevation equal to or greater than 5 mm, maximal ST elevation in lead V3 or V4 and ST elevation in the lateral leads. We concluded that systematic analysis of the 12-lead electrocardiograms recorded in the hyperacute stage is valuable for distinguishing between acute RV infarction and LV anterior wall infarction.

An ECG marker of underlying right ventricular conduction delay in the hyperacute phase of right ventricular infarction or ischemia.

Patients with extensive right ventricular (RV) infarction or ischemia often have an accompanying RV conduction delay. Such patients frequently show precordial ST-T wave elevation, which hides the late r' wave in lead V1, making it difficult to recognize the RV conduction delay during the hyperacute phase. We noted that such patients occasionally exhibited a "cove"-shaped ST-T elevation in lead V1, which strongly suggested the presence of this complication even in the hyperacute stage. This report describes three instances of RV infarction or ischemia with this characteristic electrocardiographic sign. This sign appears to be a marker of RV conduction delay during the hyperacute stage of RV infarction or ischemia.

Long-term angiographic follow-up results in patients undergoing percutaneous transluminal coronary angioplasty.

Long-term effects following percutaneous transluminal coronary angioplasty (PTCA) were examined using follow-up coronary angiography (CAG) in 49 lesions in cases in which the procedure was considered to be successful. Follow-up CAG was performed 2-5 times (average, 2.7 times) per patient during a period of 1 year to 3 years and 7 months (average, 1 year and 10 months). The luminal diameter of the PTCA sites was expressed as the percentage of the value immediately after the procedure. Narrowing by 10% or more was observed in 17 lesions 3-8 months after PTCA but in only 4 lesions on the final CAG. The luminal diameter of the PTCA site was significantly greater (p less than 0.05) 2 years after PTCA in comparison to the findings after 1 year. These results suggest excellent long-term effects at the PTCA site.

Successful coronary angioplasty for the remaining coronary artery with two completely occluded arteries with prior bypass grafting.

A 61-year-old man underwent coronary artery bypass grafting because of severe three-vessel disease. Since he had post-operative anginal attacks, coronary angiography was performed. The examination revealed the right coronary artery (RCA) and left circumflex artery (LCX) to be completely occluded, and the left anterior descending artery (LAD) showed 90% stenosis. Furthermore, the three bypass grafts (to RCA, LCX and LAD) were all occluded. The patient had severe anginal episodes despite drug therapy. Since the patient refused a second bypass operation, we performed percutaneous transluminal coronary angioplasty on the LAD. Subsequently, the stenosis of LAD was reduced to 25%, eliminating subjective episodes of angina pectoris.

[Marked ST-segment elevation in the precordial and inferior leads in right ventricular myocardial infarction: a case report].

This is a report of right ventricular infarction complicated by inferior myocardial infarction in which marked ST-segment elevation was observed in the precordial and inferior leads. A 51-year-old man was admitted with chest pain of one-half hour duration. His admission ECG showed conspicuous ST-segment elevation in the precordial and inferior leads. The maximum magnitude of the ST-segment elevation in the precordial leads was 21 mm in lead V2 and 10 mm in lead II. Echocardiography showed akinesis of the right ventricular free wall and the posterior half of the left ventricle. Angiography revealed a 90% reduction in the diameter of the right coronary artery in its proximal portion, and a normal left coronary system. Recent reports have indicated that precordial ST-segment elevation may reflect right ventricular infarction. However, there has been no previous report of marked ST-segment elevation in the precordial and inferior leads. In right ventricular infarction, the currents of injury usually occur simultaneously in the right ventricular free wall and left ventricular inferior wall, and then are electrically opposed to each other. The diffuse and marked ST-segment elevation observed in this case is thus a rare phenomenon.

Massive ST-segment elevation in precordial and inferior leads in right ventricular myocardial infarction.

This report describes a case of right ventricular infarction in which massive ST-segment elevation in the precordial and inferior leads was observed. The maximum magnitude of the ST-segment elevation in the precordial leads was 21 mm in lead V2 and that in the inferior leads was 10 mm in lead II. Angiography revealed a reduction of 90% in the diameter of the right coronary artery in its proximal portion and a normal left coronary system. Recent reports have shown that precordial ST-segment elevation may reflect right ventricular infarction. However, no previously reported instance except our case has shown massive ST-segment elevation in both the precordial and inferior leads. In right ventricular infarction, the current of injury is usually simultaneously present in the right ventricular free wall and left ventricular inferior wall, electrically opposed to each other. Thus, the diffuse and massive ST-segment elevation observed in this study seems to be a rare phenomenon.