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Various transition-metal complexes promote CC bond-forming reactions of carbon dioxide with acyclic unsaturated hydrocarbons including alkenes, alkynes, 1,3-dienes, and allenes. These reactions provide efficient methods for the synthesis of carboxylic acids and their derivatives.

Nucleophilic carboxylations of organometallic compounds, organic halides, and aromatic hydrocarbons with carbon dioxide are promoted by transition-metal catalysts or stoichiometric basic promoters. These reactions provide efficient methods for the synthesis of carboxylic acids and their derivatives.

The gene-targeting technology allows complete and selective inactivation of a specific gene to study the consequence of total absence of the gene product. The availability of such null-mutant mice enables investigators to identify the biological function of the gene product in physiological or pathophysiological conditions. This technology, popularly known as "gene knockout," can also induce more subtle mutations at the targeted site of the genome.

The role of Ca2+ was examined in regulating the binding of phorbol 12,13-dibutyrate (PdBu) to intact human platelets. Alterations in the cytosolic free Ca2+ concn. [(Ca2+]i), but not extracellular Ca2+, substantially influenced the binding parameters of the phorbol ester. Ca(2+)-depleted platelets demonstrated a significant decline in the maximal binding capacity (Bmax), an increase in equilibrium dissociation constant (Kd) and a decrease in the Hill coefficient (h), suggesting the presence of Ca(2+)-sensitive and Ca(2+)-insensitive populations of PdBu-binding sites. In 1 mM-Ca2+ buffer, thrombin (0.1 NIH unit/ml) and ionomycin (0.5 microM) evoked a rise in [Ca2+]i to approx. 300-500 nM, associated with a significant decline in Kd, but without an apparent effect on Bmax. No effect of thrombin was observed on PdBu binding in Ca(2+)-depleted platelets. Inhibition of protein kinase C (PKC) by H7 was associated with a greater thrombin-evoked [Ca2+]i transient and a decline in Kd. Staurosporine also decreased the Kd for PdBu binding. We propose that this effect of the PKC inhibitors on the Kd was also [Ca2+]i-dependent. These observations in intact platelets indicate that the primary role of agonist- or non-agonist-induced rise in [Ca2+]i is to increase the affinity of PKC for PdBu and, presumably, endogenous diacylglycerol. However, in itself a rise in [Ca2+]i does not increase the Bmax, for PdBu binding.

Magnesium deficiency in pregnant women is frequently seen because of inadequate or low intake of magnesium. Magnesium deficiency during pregnancy can induce not only maternal and fetal nutritional problems, but also consequences that might last in offspring throughout life. Many epidemiological studies have shown that restricted fetal growth, i.e. intrauterine growth retardation (IUGR), is associated with an increased risk of insulin resistance in adult life. We previously postulated that the intracellular magnesium of cord blood platelets is lower in the small for gestational age group than in the appropriate for gestational age group, suggesting that intrauterine magnesium deficiency may result in IUGR. Taken together, intrauterine magnesium deficiency in the fetus may lead to or program the insulin resistance after birth. We hypothesize that intrauterine magnesium deficiency may induce a metabolic syndrome in later life. Prospective studies will further clarify whether infants with IUGR induced by magnesium deficiency are at higher risk for metabolic syndromes in childhood or adulthood.

Free intracellular Mg2+([Mg2+]i) can potentially integrate the signals from hormones, cellular metabolism and organismal ion homeostasis and affect the activities of ion channel and other effectors. Interest in [Mg2+]i has been heightened by recent reports that small changes in [Mg2+]i in the physiological range can significantly modulate important cellular functions. In addition, a variety of new evidence shows that [Mg2+]i instantaneously changes following stimulation with various biologically active substances. These observations suggest that [Mg2+]i may act as a second messenger.

Azithromycin (AZM), 10% fine granules or 100 mg capsules, were given orally to 27 children with various pediatric infections. The results of the study are shown below. 1. Pharmacokinetic investigation. We studied plasma and urinary concentrations after 100 mg AZM capsules were given. One patient received 8.3 mg/kg of AZM once a day for 3 days, and AZM concentration in plasma was 0.033 microgram/ml 48 hours after the final dosing. Doses of 8.3 and 12.5 mg/kg body weight of AZM were respectively given to two patients once daily for 3 days. As a result, AZM concentrations in urine during a period between 96 and 120 hours post-dosing were 1.67 and 4.53 micrograms/ml, respectively, and urinary excretion rate in 120 hours after the first dosing was 10.54% in the patient that was given 12.5 mg/kg. 2. Clinical investigation. Clinical efficacies were examined in 24 patients. Excellent results were obtained in 7 patients, good results in 14 patients, hence the clinical efficacy rate was 87.5%. Bacteriologically, Haemophilus influenzae strains isolates from 2 patients were eradicated in 1 and decreased in the other. Safety was evaluated in 26 patients. An adverse reaction was observed in 1 patient (urticaria). Abnormal laboratory test results were observed in 2 patients, decreased WBC in 1 and elevation of eosinophils in the other. The above results suggest that AZM is a useful oral antibiotic for pediatric patients with infection with susceptible organisms.

Cefozopran (CZOP, SCE-2787), a new parenteral cephem, was evaluated for its antibacterial activity and clinical efficacy. CZOP, 24.0-78.0 mg/kg/day, was given to 11 pediatric patients in 3 dose a day via 30-minute drip infusion. Clinically evaluated were nine patients including 4 with acute pneumonia, 2 with urinary tract infections, 2 with lymphadenitis and 1 with sepsis. Two patients were excluded because of possible non-bacterial infections. Clinical efficacies were excellent in 5, good in 3 and fair in 1. Bacteriological responses were confirmed for 5 strains in 5 patients. Four strains were eradicated, but one strain was not. MICs of CZOP were equal to those of ceftazidime. Side effects or abnormal laboratory test results were observed in 3 patients; diarrhea in 1, elevated GPT in 1 and thrombocytosis in 1, but none of them was significant.

The characteristics of cardiac rupture associated with thrombolytic therapy for acute myocardial infarction (MI) were studied in the hearts of 10 autopsy patients, 7 men and 3 women aged 41-80 years (mean 59.9 +/- 13.2 years), who died of rupture of the free wall of the left ventricle following acute MI. The site of rupture was examined histologically and the percentage areas of living myocytes, the processes of organization, necrosis and degeneration, and hemorrhage were compared in four patients who received thrombolytic therapy (group R) and six patients without thrombolytic therapy (group N). There were four pathological findings at the site of rupture: necrosis, neutrophil infiltration, hemorrhage, and evidence of the process of absorption. Group R consisted of two patients with hemorrhage, one with absorption, and one with unsuccessful reperfusion and neutrophilic infiltration. Group N included three patients with necrosis, two with neutrophilic infiltration, and one with hemorrhage. The percentage area involved by necrosis and degeneration was significantly lower in group R than in group N. Therefore, local stress produced by more surviving myocardium around the smaller necrosis area and the weakness of myocardium due to hemorrhage and absorption may provoke cardiac rupture in acute MI patients receiving thrombolytic agent.

The effects of residual stenosis after intracoronary thrombolysis (ICT) on the hospital course and on left ventricular function were investigated in 94 patients with acute myocardial infarction. The in-patient hospital events including death, post-infarction angina, and re-infarction occurred in 6 of 24 (25%) patients with 100-99% residual stenosis (Group I), 18 of 55 (32.7%) patients with 95-90% stenosis (Group II) and one of 15 (7%) patients with 75% or less stenosis (Group III), suggesting that the presence of severe residual stenosis could be associated with the occurrence of in-patient hospital events. However, re-infarction occurred in only 3.6% of Group II patients. In an analysis of left ventricular function, global and regional wall motion was significantly improved in this group of patients, compared with patients who had no reperfusion (Group I). What is more, the degree of the improvement in wall motion in Group II, despite the severe stenosis, was the same as that in Group III with 75% or less stenosis. It was concluded that further intervention following thrombolysis may not be necessarily required for patients who underwent reperfusion without filling delay, even if the residual stenosis is greater than 90%.

To explore the etiology of altered Ca metabolism in essential hypertension, we studied parameters, i.e., maximal initial reaction velocity (Vmax) and Michaelis constant (Km), of Ca activation kinetics of Ca2(+)-ATPase in membrane fractions (isolated by a sucrose gradient) from platelets of blacks and whites, 27 of whom were essential hypertensives, 17 of whom were normotensives with a family history of essential hypertension, and 10 of whom were normotensives without a family history of the disease. The Vmax of hypertensives was significantly lower than in normotensives without a family history of essential hypertension (hypertensives, 14.99 +/- 1.71 nmol Pi.mg protein-1.min-1; normotensives, positive family history, 22.67 +/- 3.17 nmol Pi.mg protein-1.min-1; normotensives, negative family history, 27.54 +/- 4.37 nmol Pi.mg protein-1.min-1; overall, P = 0.0078). The Km was lower in both hypertensives and normotensives with a positive family history of essential hypertension as compared with normotensives with a negative family history of the disease (hypertensives, 1.70 +/- 0.23 microM; normotensives, positive family history, 1.38 +/- 0.2 microM; normotensives, negative family history, 2.79 +/- 0.58 microM; overall, P = 0.0251). Furthermore, the Km in whites was inversely related to plasma renin activity (r = 0.50; P less than 0.005). We propose that a lower Vmax for Ca2(+)-ATPase may play a role in the higher level of free Ca in platelets of essential hypertensives and that a higher affinity of the enzyme to Ca may reflect a process compensating for the lower Vmax. We also suggest that a higher Km for Ca2(+)-ATPase in juxtaglomerular cells of whites would result in blunting the release of renin.

The (H+,K+)ATPase-enriched microsomal fraction prepared from hog gastric mucosa by sucrose density gradient centrifugation was effectively solubilized with Emulgen, with apparent preservation of the enzyme activity, and then the ATPase was highly purified by polyethylene glycol fractionation, and Blue Sepharose CL-6B and amino-hexyl Sepharose chromatographies. The purified enzyme showed a single band, with an apparent molecular mass of approximately 94 kDa, on SDS-PAGE, and exhibited both K+-ATPase and K+-stimulated-p-nitrophenyl phosphatase (pNPPase) activities. The optimum pH for the ATPase activity was 7.0. Amino acid analysis of the purified enzyme showed that it contains a large amount of hydrophobic amino acid (42%) and a small amount of glucosamine and galactosamine. The rabbit antibody monospecific for the ATPase, in the Ouchterlony double immunodiffusion and Western blotting tests, markedly inhibited both the K+-ATPase and K+-pNPPase activities.

A 25-year-old man was admitted to Juntendo University Hospital with chief complaints of nocturnal dyspnea and shortness of breath on Sept. 22, 1983. He had no history of rheumatic fever or bacterial endocarditis. He was violently kicked in the chest while practicing Shorinji-Kempo (Karate) in July 1977. His heart murmur was first noticed in April 1978, but he was asymptomatic for six years after the accident until transient nocturnal dyspnea developed January 1983. Physical examination on admission revealed a grade 4/6 apical holosystolic murmur, a markedly accentuated third sound, and hepatomegaly of two finger breadth in the right midclavicular line. An electrocardiogram revealed sinus tachycardia (100/min), left atrial overload and left ventricular hypertrophy. Chest radiography showed slight cardiac enlargement with a cardiothoracic ratio of 55%, and slightly increased pulmonary vascular markings. Two-dimensional echocardiography showed a markedly prolapsed posterior mitral leaflet and fluttering in diastole. Cardiac catheterization showed elevated pressure of pulmonary capillaries (a: 16, v: 30, mean: 19 mmHg), the pulmonary artery and the right ventricle. Left ventriculography revealed grade four (Sellers) mitral regurgitation. Mitral valve replacement was performed on October 13, 1983. A chorda tendinae supporting the posterior leaflet of the mitral valve was found to be ruptured just above its origin from the posterior papillary muscle. Histological examination of the resected valve showed increased spongiosa tissue which mimicked so-called myxomatous changes, but it seemed preferable to interpret this as a "secondary change due to increased hemodynamic stress" rather than the "primary change".

The purpose of this study was to determine whether two-dimensional echocardiography (2DE) can differentiate ischemic myocardial disease (IMD) from dilated cardiomyopathy (DCM). The subjects consisted of six cases of IMD which showed left ventricular dilatation (LVDd greater than or equal to 60 mm) and diffuse abnormality of wall motion, but did not show obvious localized myocardial infarction or left ventricular aneurysm on 2DE, and 16 cases of DCM. Two cases of IMD had previous myocardial infarction, and five cases of DCM had cardiomegaly following myocarditis. A short-axis image of the left ventricle was recorded at the chordal and the papillary muscle levels. Each image was divided into 4 segments, which were comprised of the septum, anterior wall, lateral (posterolateral) wall, and posterior (posteromedial) wall. Regional wall motion abnormality with reference to systolic thickening was analyzed qualitatively in each segment. The results were as follows: In ECG findings in IMD group, only one case showed abnormal Q waves and five cases showed left ventricular hypertrophy (LVH) similar to intraventricular conduction defect. On the other hand, in DCM group seven cases showed abnormal Q waves and five cases showed LVH. Two cases of IMD had two-vessel disease and four three-vessel disease, respectively. Left ventricular ejection fraction by cine-angiography ranged from 0.10 to 0.39 (mean 0.24) in IMD group and from 0.22 to 0.42 (mean 0.36) in DCM group. Mean LVDd showed no significant difference between these two groups. Five cases of DCM showed marked left ventricular dilatation (LVDd greater than or equal to 75 mm), but there were no such cases in IMD group. B-B' step was recognized in only one case of IMD, though it was present in eight cases in DCM. In regional wall motion, incidence of asynergy such as akinesis or dyskinesis was higher in IMD group than in DCM group. Left ventricular asynergy was more serious in the posteromedial wall than the posterolateral wall at the same image in five cases of IMD. However, in 12 cases of DCM, the degree of asynergy was equal at the both walls. In conclusion, it is recommended to examine echocardiographically the extent of severe asynergy in the posteromedial and posterolateral walls in order to differentiate IMD from DCM.