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Pyridoxal-5'-phosphate-dependent cysteine synthases synthesize l-cysteine from their primary substrates, O-acetyl-l-serine (OAS) and O-phospho-l-serine (OPS), and their secondary substrate, sulfide. The mechanism by which cysteine synthases recognize OPS remains unclear; hence, we investigated the OPS recognition mechanism of the OPS sulfhydrylase obtained from Aeropyrum pernix K1 (ApOPSS) and the OAS sulfhydrylase-B obtained from Escherichia coli (EcOASS-B), using protein engineering methods. From the amino acid sequence alignment data, we found that some OPS sulfhydrylases (OPSSs) had a Tyr corresponding to the Phe225 and Phe141 residues in ApOPSS and EcOASS-B, respectively, and that the Tyr residue could facilitate OPS recognition. The enzymatic activity of the ApOPSS F225Y mutant toward OPS decreased compared with that of the wild-type; the kcat value decreased 2.3-fold during cysteine synthesis. X-ray crystallography results of the complex of ApOPSS F225Y and F225Y/R297A mutants bound to OPS and l-cysteine showed that kcat might have decreased because of the stronger interactions of the reaction product phosphate with Tyr225, Thr203, and Arg297, and that of the l-cysteine with Tyr225. The specific activity of the EcOASS-B F141Y mutant toward OPS increased by 50-fold compared with that of the wild-type. Thus, a Tyr within a cysteine synthase corresponding to the Phe225 in ApOPSS and Phe141 in EcOASS-B could act as a key residue for classifying an unknown cysteine synthase as an OPSS. The elucidation of the substrate recognition system of cysteine synthases would enable us to effectively classify cysteine synthases and develop pathogen-specific drug targets, as OPSS is absent in mammalian hosts.

Twenty-one patients undergoing mitral valve replacement (MVR) with either isolated or combined valvular procedure were investigated to determine the ef fect of randomized and prospective administration of L-carnitine (car) chloride on myocardial function. Carnitine chloride (1800 mg/day, for seven consecu tive days just prior to MVR) was given orally to 9 patients (car-treated group) who were compared with 12 car-untreated patients (control group) subjected to the same procedure. Valve replacement was performed using the Bjork-Shiley mechanical prosthesis in aortic and mitral position and bioprosthesis in tricuspid position in both groups under cardiopulmonary bypass (CPB) associated with cold potassium-magnesium cardioplegia and systemic hypothermia. Preopera tive and intraoperative clinical profile (age, functional class, duration of aortic clamp and CPB, and level of hypothermia) was well matched in both groups. Free, short-chain acyl, long-chain acyl, and total Car were measured in the papil lary muscle excised adjacent to the free wall of the left ventricle at the time of valvular surgery. Heart rate and mean arterial pressure did not differ between the two groups. Cardiac index was 3.44 ± 0.08 and 3.82 ± 0.13 L/m2/min in the control and car-treated groups, respectively, (p < 0.05). Dobutamine (DOB) infusion rate was 8.55 ± 0.73 and 5.57 ± 0.95 μg/kg/min in the control and car-treated groups, respectively (p < 0.05). Left ventricular stroke work index (LVSWI)/DOB ratio was 4.50 ± 0.65 and 8.16 ± 1.72 g*m/m 2/beat/unit of DOB, in the control and car-treated groups, respectively (p < 0.05). Long-chain acyl carnitine was 0.224 ± 0.031 and 0.460 ± 0.096 nmoL/mg noncollagenous protein in the control and the car-treated groups, respectively (p These findings suggest that pretreatment with L-carnitine chloride appears to be effective in improving myocardial function in the early phase of reperfu sion following surgery and that long-chain acyl carnitine may play a key role in the enhancement of carnitine-meditated mitochondrial metabolic process.

This study was undertaken in order to clarify the clinical characteristic features and surgical results of coronary artery bypass grafting (CABG) in patients over 65 years of age (group III, n = 43). These patients were compared with 2 other groups of patients, one aged between 50 and 59 years (group I, n = 88) and another aged between 60 and 64 years (group II, n = 54), with respect to mortality, morbidity and late survival. CABG was performed with the saphenous vein under cold K-Mg-cardioplegia with systemic hypothermia. The hospital mortality was 2.3, 3.7, and 4.7 per cent in groups I, II and III, respectively, although no operative mortality was noted in any group. The number of coronary artery lesions increased with age, however, the left ventricular ejection fraction was relatively better preserved in the aged patients than in the younger ones. The 5-year survival rates were 93.4, 95.1 and 96.9 per cent in groups I, II and III, respectively, with most of the late deaths occurring within a year after CABG in each group. In the aged patients, postoperative functional recovery was delayed in the liver and kidney, and postoperative psychosis was not infrequent. The results of this study, indicating a low operative mortality and satisfactory late survival rate, thus strongly support CABG for the aged. Nevertheless, the prevention of postoperative complications is also extremely important for reducing hospital mortality.

We reported a case of pycnodysostosis and review of 67 cases in the Japanese literature, especially on its oral and maxillofacial aspects. The following oral and maxillofacial findings were commonly reported in most cases: 1. mandibular angle loss, 2. hypoplasia of the maxilla and mandible, 3. grooved palate and 4. malpositioned teeth. Other findings reported occasionally included: osteomyelitis, anterior cross bite, mandibular fracture, permanent tooth missing, hypercementosis, microdontia, delayed eruption of permanent tooth, persistence of deciduous tooth, enamel hypoplasia, obliterated pulp chamber, macroglossia, hypoplasia of dental root and dentin hypoplasia.

A 54-year-old man with a left ventricular free wall rupture following acute anterior myocardial infarction underwent a repair surgery with percutaneous cardiopulmonary support (PCPS). During surgery and postoperatively, PCPS provided sufficient support flow. The patient was successfully weaned from PCPS on the 15th postoperative day and discharged subsequently. In the management of cardiac rupture patients, PCPS has the merit of preventing rupture progression and the advantage of recovery of pulmonary function. However, there are several problems to solve. The support effectiveness and recovery of the patient's heart should be carefully evaluated. Effective left heart decompression also needs to be established. Heparin-coated circuits still need proper anticoagula-tion treatment to prevent thrombus formation especially while support flow is low. A circuit construction that allows easier maintenance and safer exchange of oxygen-ators and pump heads is suggested. Ischemia of the cannulated leg should be prevented by femoral artery perfusion.

Background The relation between episodes of acute rejection and the development of graft coronary arteriosclerosis remains controversial. We examined the hypothesis that acute rejection episodes accelerate graft coronary arteriosclerosis lesion formation in rabbit allografts. Methods and Results A control group (n=5) received cyclosporine 5 mg · kg −1 · d −1 for 6 weeks after heterotopic heart transplantation. In a rejection group (n=5), cyclosporine was omitted for 4 days at 1 and 4 weeks after transplantation. We studied cross sections of grafted hearts at 6 weeks and evaluated myocardial rejection grade, incidence, and severity and cell composition of intimal lesions in multiple coronary artery profiles. Episodic withdrawal of cyclosporine augmented myocardial rejection (International Society for Heart and Lung Transplantation grades 0, 0, 0, 0, and 1A in the control group to grades 1A, 1B, 2, 3A, and 3B in the rejection group). Episodes of acute rejection significantly increased the incidence (7.8±2.7% to 49.7±1.9%) and severity (from grade 0.10±0.04 to 0.79±0.24) of intimal thickening in graft coronary arteries. Most intimal lesions consisted of smooth muscle cells and contained various degrees of T-lymphocyte infiltration but sparse macrophages. Conclusions In this experimental model, episodes of acute rejection precipitated by cyclosporine withdrawal accelerated the development of graft vascular lesion formation. Activation of vascular cells and leukocyte recruitment during acute rejection may thus contribute to the pathogenesis of graft arteriosclerosis.

The myocardial distribution and concentration of carnitine and its fractions was studied in 11 patients with mitral valve disease not associated with congestive heart failure (CHF). The plasma concentration of carnitine was found to be identical to the normal values documented in the literature. The left ventricular papillary muscle had the highest concentrations of total, short-acyl, long-acyl, and free carnitine, being significantly higher than those of the right ventricle, while the right atrial appendage had the lowest values of all fractions of carnitine. The proportion of long-acyl carnitine to total carnitine was significantly greater in the left ventricle than in either the right atrium or the atrial septum, and other carnitine fractions were identical in all cardiac chambers. Our results suggest that in the compensated heart with mitral valve disease, carnitine and its fractions are greatest in the left ventricle in the muscles of all cardiac chambers, and that long-acyl carnitine is most likely to be linked to the cardiac muscle demanding a higher cardiac performance.

The thiobarbituric acid (TBA) reaction method established by Yagi to determine the lipid peroxide level in serum and animal tissues was applied to isolated mitochondria with some modifications. The TBA reaction was carried out in acetic acid (pH 2.0) in the presence of 0.7 % sodium dodecyl sulfate at 95°C for 45 min. Chloroform was used to remove the lipid and protein from the reaction mixture. An aqueous layer was used for spectrophotometric measurement at 532.5 nm to determine the TBA reaction product with lipid peroxide. To evaluate the TBA assay system, the lipid peroxide content of mitochondrial suspensions exposed to ultraviolet light was examined. The lipid peroxide formed in mitochondria was proportional to the dose of ultraviolet energy. The lipid peroxide of methyl linoleate exposed to ultraviolet light was determined both with the TBA reaction and with the hydroperoxide reaction. The linear increase in TBA values following UV exposure was similar to the increase of hydroperoxide values determined iodometrically. The TBA assay was shown to be a good predictor of lipid peroxide formed in mitochondria. This assay system is useful for lipid peroxide determination in various tissues: epidermis, Ehrlich ascites tumor cells and B-16 melanoma culture cells.

In this paper, the influence of work speed, number of sparkout and forced vibration on the roughness of ground surface in the perpendicular section to grinding direction was investigated experimentally. The influence of work speed on the roughness of ground surface in the parallel one was investigated experimentally, too. On the other hand, using the experimental results of the distribution in depth for the position of grain cutting edges and the distribution of grain tip angles in the wheel surface layer, theoretical values of the roughness were calculated and compared with experimental values. Further, it was made clear by Monte Carlo simulation that the influence of elastic displacement of grain cutting edges on the roughness of ground surface in the perpendicular section to grinding direction was not so large.

If a flow obstruction such as a spacer is set in a boiling two-phase flow within an annular channel, the inner tube of which is used as a heater, the temperature on the surface of the heater tube is severely affected by the existence of the spacer. In some cases the spacer has a cooling effect, and in the other case it causes the dryout of the cooling liquid film on the heating surface resulting in the burnout of the tube. But the thermo-fluid dynamics mechanism to cause burnout near the spacer is not still clear. In the present paper we discuss temperature fluctuation characteristics in relation to the change of the flow configuration near the spacer in transient boiling two-phase flow. The transient parameters are the heat flux, the mass flow rate, and the inlet quality.