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This study proposes the laser-ignited micromotor (LIMO), which is a new propulsion system for CubeSats to overcome the problems associated with conventional chemical propellants. The solid propella...

The purpose of this study was to investigate the changes in tongue-palatal contact patterns using electropalatography (EPG) before and after sagittal split ramus osteotomy (SSRO) in patients with mandibular prognathism. Nine clients who underwent SSRO for mandibular setback and seven control subjects were participated in this study. Tongue-palatal contact patterns for /t/, /s/ and /k/ production were investigated using EPG before surgery and 3 months after surgery. The mean value of whole total of palate contact (WT) in the maximum contact frame was examined before and after SSRO. The correlation quantity between the change of center of gravity (COG) value and the amount of mandibular setback was also evaluated. The mean value of WT for /t/ and /s/ significantly increased after SSRO, and the EPG pattern became normal. However, a remarkable change in WT for /k/ was not observed, and the mean value was significantly larger in the SSRO group before and after surgery than in the control group. A negative correlation between COG variation and the amount of mandibular setback for /t/ and positive correlation for /s/ was observed. This study demonstrated that tongue-palatal contact patterns for /t/ and /s/ articulation improved clearly after SSRO. There was a significant correlation between COG variation and the amount of mandibular setback. However, no significant change was detected through perceptual assessment before and after SSRO. Further investigation is needed to determine whether these results will change over time.

We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (

Previous studies showed that a programmed freezer with magnetic field can maintain a high survival rate of mesenchymal stem cells (MSCs). The purpose of this study was to evaluate the influences of magnetic field during freezing and thawing on the survival of MSCs isolated from rat bone marrow. The cells were frozen by a normal programmed freezer or a programmed freezer with magnetic field (CAS-LAB1) and cryopreserved for 7 days at -150 °C. Then, the cells were thawed in the presence or absence of magnetic field. Immediately after thawing, the number of surviving or viable cells was counted. The cell proliferation was examined after 1-week culture. Cryopreserved MSCs which were frozen by a normal freezer or a CAS freezer were transplanted into bone defects artificially made in calvaria of 4-week-old rats. Non-cryopreserved MSCs were used as a control. The rats were sacrificed at 8, 16, or 24 weeks after transplantation and the bone regeneration area was measured. Proliferation rates of MSCs after 1 week were significantly higher in the CAS-freezing-thawing group than in the CAS-freezing group. The extent of new bone formation in the CAS-freezing-thawing group tended to be larger than in CAS-freezing group 24 weeks after transplantation. These results suggest that a magnetic field enhances cell survival during thawing as well as freezing.

Mesenchymal stem cells (MSCs) can be used for regeneration of various organs and tissues. A previous study revealed that cryopreserved MSCs, which were frozen by a programmed freezer with a magnetic field (Cells Alive System: CAS) and cryopreserved for 7 days in a -150°C deep freezer, can maintain high survival and proliferation rates while retaining both adipogenic and osteogenic differentiation abilities. The purpose of this study was to examine MSC viability and tissue regenerative ability after long-term cryopreservation using a CAS freezer. MSCs were isolated from rat femora bone marrow and cryopreserved in a -150°C deep freezer (CAS group) or directly cryopreserved in a deep freezer (Direct group). After 3 years, the cells were thawed and the number of viable cells was counted. Cell proliferation was also examined after 14 days in culture. For histological examination, forty 4-week-old Fischer 344 male rats received bone and sagittal suture defects with a diameter of 6.0mm, and MSCs (CAS or Direct group) cryopreserved for 1 year were grafted with membranes. Non-cryopreserved MSCs (Control group) were transplanted to an additional twenty rats. The rats were sacrificed at 4, 8, 16, and 24 weeks after surgery. The parietal bones, including the sagittal suture, were observed under a light microscope and the extent of bone regeneration was measured. Our results indicate that MSCs survival and proliferation rates were significantly higher in the CAS group than in the Direct group. In the Control and CAS groups, a large amount of new bone formation and a suture-like gap was identified 24 weeks after transplantation, whereas only a small amount of new bone formation was observed in the Direct group. These results suggest that the CAS freezer is amenable to long-term cryopreservation of MSCs, which can be applied to the regeneration of various tissues, including bone tissue with suture-like gap formation.

Previous studies have revealed that orthodontic force affects dental pulp via the rupture of blood vessels and vacuolization of pulp tissues. We hypothesized that pulp tissues express inflammatory cytokines and regulators of odontoclast differentiation after excess orthodontic force. The purpose of this study was to investigate the effects of tensile force in human pulp cells and to measure inflammatory root resorption during tooth movement in pulpless rat teeth.After cyclic tensile force application in human pulp cells, gene expression and protein concentration of macrophage colony-stimulating factor, receptor activator of nuclear factor kappa-B ligand, interleukin-1 beta, and tumor necrosis factor alpha were determined by real-time polymerase chain reaction and enzyme-linked immunoassay. Moreover, the role of the stretch-activated channel was evaluated by gadolinium (Gd(3+)) treatment. The upper right first molars of 7-week Wistar rats were subjected to pulpectomy and root canal filling followed by mesial movement for 6 months.The expression of cytokine messenger RNAs and proteins in the experimental group peaked with loading at 10-kPa tensile force after 48 hours (P.01). Gd(3+) reduced the expression of these cytokine messenger RNAs and protein concentrations (P.01). The amount of inflammatory root resorption was significantly larger in the control teeth than the pulpectomized teeth (P.05).This study shows that tensile forces in the pulp cells enhance the expression of various cytokines via the S-A channel, which may lead to inflammatory root resorption during tooth movement. It also suggests that root canal treatment is effective for progressive severe inflammatory root resorption during tooth movement.

The purpose of this study is to evaluate the sterilization effects of a newly developed low temperature multi gas plasma jet on oral pathogenic microorganisms (Streptococcus mutans [S. mutans], Lactobacillus fermentum [L. fermentum], Aggregatibacter actinomycetemcomitans [A. actinomycetemcomitans]). Plasma gas which generated from O2, N2, Ar and 50% (O2+N2) was irradiated to the microbes. Effect of O2 plasma irradiation on S. mutans under scanning electron microscopy (SEM) was also observed. O2 plasma was directly applied to dental plaque on human extracted tooth. Then, the depth of enamel resorption area was noted by nanoscale hybrid microscope. O2 had the best sterilizing effect for all microbes. The potent bactericidal effect of plasma irradiation was also observed by SEM. Decalcification of enamel was noted significantly lower in plasma irradiated tooth surface compared to no plasma exposure group. These findings revealed that multi gas plasma jet has great potential to be used for dental treatment.

Background: Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were randomly allocated to first-line treatment with a calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Methods: We recruited 265 (93 for CCB, 71 for ACEI and 101 for ARB) patients who completed the genomic study. Home blood pressure was measured for 5 days off-treatment before randomization and for 5 days after 2-4 weeks of randomized drug treatment. Genotyping was performed by 500K DNA microarray chips. The blood pressure responses to the three drugs were analyzed separately as a quantitative trait. For replication of SNPs with p < 10(-4), we used the multicenter GEANE study, in which patients were randomized to valsartan or amlodipine. Results: SNPs in PICALM, TANC2, NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication. Conclusion: Our approach, the first based on high-fidelity phenotyping by home blood pressure measurement, might be a step in moving towards the personalized treatment of hypertension. Original submitted 29 April 2013; Revision submitted 14 August 2013. ispartof: Pharmacogenomics vol:14 issue:14 pages:1709-21 ispartof: location:England status: published

This case report describes the treatment of a case involving a skeletal Class II facial profile with a gummy smile. While treating a facial profile and a gummy smile, the outcome may not always be successful with orthodontic therapy alone. For this reason, surgical therapy is often chosen to gain an esthetic facial profile and a good smile. However, sometimes the patients reject surgical treatment and an alternative method must be considered. Skeletal anchorage systems such as miniscrews are now frequently used for correcting severe malocclusion that should be treated by surgical therapy. In this case report, we treated a skeletal Class II malocclusion with a convex profile and a gummy smile using miniscrews, which were placed in the upper posterior and anterior areas. The active treatment period was 3.5 years, and the patient's teeth continued to be stable after a retention period of 36 months.

At the present time, there are no reports in the literature on the treatment of temporomandibular joint disorder (TMD) by intrusion of molars using mini-screws. This case report describes the treatment for a female patient, aged 19 years seven months, with a TMD and an excessive lower anterior facial height. Overjet and overbite were +5.0 mm and +0.5 mm, respectively. The patient had a history of orthodontic treatment in which her first premolars were all extracted. During the first orthodontic treatment, a clockwise mandibular rotation was observed as a result of the increase of posterior dentoalveolar height. She had temporomandibular joint (TMJ) pain during mouth opening and complained of difficulty in eating due to masticatory dysfunction. The pretreatment Schuller views of both TMJ showed a posterior condyle position. In order to correct the overjet, molar relationship and the mandibular condyle position, a miniscrew was inserted into the palatal region of the upper first molar to intrude the upper posterior teeth. As the upper molars were intruded, the overjet was decreased, and a class I molar relationship was achieved by a counterclockwise mandibular rotation. After one year of treatment, an acceptable occlusion was achieved, and the condyle moved into centric position in the glenoid fossa. The patient's teeth continued to be stable, and she had no pain in TMJ after a retention period of three years. The result of this treatment showed that molar intrusion using miniscrew anchorage is effective for treatment of a TMD patient with a posterior condyle position.

The purpose of this study was to establish a long-term tooth cryopreservation method that can be used for tooth autotransplantation. Human periodontal ligament (PDL) cells were frozen in 10% dimethyl sulfoxide (Me(2)SO) using a programmed freezer with a magnetic field. Cells were cryopreserved for 7 days at -150 degrees C. Immediately after thawing, the number of surviving cells was counted and the cells were cultured; cultured cells were examined after 48 h. Results indicated that a 0.01 mT of a magnetic field, a 15-min hold-time, and a plunging temperature of -30 degrees C led to the greatest survival rate of PDL cells. Based on these findings, whole teeth were cryopreserved under the same conditions for 1 year. The organ culture revealed that the PDL cells of cryopreserved tooth with a magnetic field could proliferate as much as a fresh tooth, although the cells did not appear in the cryopreserved tooth without a magnetic field. Histological examination and the transmission electron microscopic image of cryopreserved tooth with a magnetic field did not show any destruction of cryopreserved cells. In contrast, severe cell damage was seen in cells frozen without a magnetic field. These results indicated that a magnetic field programmed freezer is available for tooth cryopreservation.

This case report describes the treatment of a skeletal Class III malocclusion with autotransplantation of a cryopreserved tooth. To gain an esthetic facial profile and good occlusion, extraction of bimaxillary premolars and surgical therapy were chosen. The patient had chronic apical periodontitis on the lower left first molar. Although she did not feel any pain in that region, the tooth was considered to have a poor prognosis. Therefore, we cryopreserved the extracted premolars to prepare for autotransplantation in the lower first molar area because the tooth would probably need to be removed in the future. The teeth were frozen by a programmed freezer with a magnetic field (CAS freezer) that was developed for tissue cryopreservation and were cryopreserved in −150°C deep freezer. After 1.5 years of presurgical orthodontic treatment, bilateral sagittal split ramus osteotomy was performed for mandible setback. Improvement of the facial profile and the occlusion were achieved in the retention phase. Six years after the initial visit, the patient had pain on the lower left first molar, and discharge of pus was observed, so we extracted the lower left first molar and autotransplanted the cryopreserved premolar. Three years later, healthy periodontium was observed at the autotransplanted tooth. This case report suggests that long-term cryopreservation of teeth by a CAS freezer is useful for later autotransplantation, and this can be a viable technique to replace missing teeth.

C-reactive protein (CRP) is one of the important risk factors for atherosclerosis, and its serum level is lowered by popular cholesterol-lowering drugs, statins. This study was undertaken to examine the changes of CRP levels during dextran-sulfate (DS) low-density lipoprotein (LDL) apheresis. In 15 apheresis sessions in seven patients with severe hypercholesterolemia (four men and three women, aged between 36 and 70 years), changes in CRP levels were examined. The efficiency in adsorption of CRP with DS column was evaluated by measuring CRP levels in both pre- and post-column plasma. In one patient, the effect of repeated apheresis sessions on CRP preapheresis levels was examined. The changes in interleukin (IL)-6 plasma levels were also examined in six sessions. Although IL-6 levels after 3,000 mL-plasma treatment rose to 170% of preapheresis levels, CRP levels decreased significantly (from 1.91 +/- 0.49 mg/L to 0.89 +/- 0.24, P < 0.01). C-reactive protein was almost completely adsorbed by the DS column and CRP preapheresis levels were decreased gradually by repetition of apheresis. CRP, a novel risk factor of atherosclerosis, was effectively removed by DS-LDL apheresis. The decrease in CRP plasma levels may be involved in prevention of atherosclerotic vascular diseases due to DS-LDL apheresis.

Experimental studies have revealed that stent configuration influences intimal hyperplasia. The purpose of this study was to evaluate clinical outcomes for 2 stent designs in a randomized trial with quantitative coronary angiography (QCA) and intravascular ultrasonography (IVUS).We randomly assigned 100 patients with 107 lesions and symptomatic coronary artery disease to deployment of a Multilink stent (Advanced Cardiovascular Systems, Guidant, Santa Clara, Calif) or a GFX stent (Applied Vascular Engineering, Santa Rosa, Calif) with IVUS guidance. QCA and IVUS studies were performed before and after intervention and at follow-up (4.2 +/- 1.0 months).There were no significant differences in baseline characteristics and QCA and IVUS parameters before and after intervention between the 2 groups. However, minimal lumen diameter at follow-up was significantly larger in the Multilink group (2.46 +/- 0.59 vs 2.08 +/- 0.79 mm, P.05). Maximal in-stent intimal hyperplasia was significantly larger in the GFX group (2.9 +/- 1.7 vs 1.8 +/- 1.2 mm(2), P.01). The restenosis rate differed between the 2 groups (Multilink 4% vs GFX 26%, P =.003). In multiple stepwise logistic regression analysis, the only predictor that significantly correlated with restenosis was stent type (P.01). The odds ratio for the GFX stent-treated vessels was 18.65 (95% confidence interval 2.10-165.45).With deployment of the GFX stent, a thicker neointima develops within the stent. Stent configuration may affect clinical outcomes.

Several different techniques of low-density lipoprotein (LDL) apheresis are available for management of severe hypercholesterolemia. Among them, the adsorption system with a dextran-sulfate cellulose (DSC) column is most widely used. In addition to adsorption of LDL, DSC adsorbs plasma constituents that have the following characteristics: proteins containing apolipoprotein B (Lp[a]); proteins involved in the initial contact phase of the intrinsic coagulation pathway (coagulation factor XII, high-molecular-weight kininogen and prekallikrein); factors with lipophilic characteristics (coagulation factor VII, coagulation factor VIII, and vitamin E); and proteins with adhesive or other characteristics (von Willebrand factor, fibronectin, serum amyloid P component, hepatocyte growth factor). The adsorption of these proteins seems to ameliorate prevention or regression of atherosclerosis. Moreover, plasma treatment by the DSC column may be useful for treatment of inexorable diseases, such as amyloidosis. On the other hand, the DSC column generates bradykinin by activation of the initial contact phase of the intrinsic coagulation pathway. Bradykinin generation may explain the functional improvement in the circulatory system, as well as hypotension during LDL apheresis, which is observed in patients taking ACE inhibitors.

The authors report a 47-year-old man with Becker-type muscular dystrophy presenting with dilated cardiomyopathy. Left ventriculography showed diffuse severe hypokinesia: left ventric ular end-diastolic volume index 193 mL/m2, left ventricular end-systolic volume index 143 mL/m 2, and left ventricular ejection fraction 26%. Skeletal muscle biopsy demonstrated a dystrophic process. Genetic analysis revealed a deletion of exon 4. There was a difference in immunos taining pattern between skeletal muscles and cardiac muscles. Severe cardiac dysfunction in this case may be associated with the damage in dystrophin-deficient fibers.

We report an unusual case of acute myocardial infarction attributable to obstruction of a discrete coronary aneurysm in a 54-year-old man. Although coronary angioplasty and thrombolysis were unsuccessful, serial arteriography showed spontaneous recanalization, and no spasm was induced by ergonovine. We discuss its mechanism.

The aim of this study was to assess the grade of heterogeneous disturbance in the renal cortical circulation using dynamic computed tomography and to investigate the relationship between the heterogeneity of renal cortical circulation and hypertension. We studied 125 patients who underwent dynamic computed tomography (CT) for various abdominal diseases and had no serious hemodynamic abnormalities. In dynamic computed tomography under appropriate conditions, each pixel (image element), less than 1 mm 2 , has a CT number that is in proportion to the concentration of contrast media, which reflects the blood volume in the pixel. The image was constructed at the hilus level about 50 s after the start of a continuous infusion of contrast medium. The mean and standard deviation were calculated from the CT numbers in the renal cortex. The coefficient of variation, ie, the standard deviation divided by the mean value, was used as the index of the heterogeneity of renal cortical circulation. The coefficient of variation was significantly ( P .001) greater in the hypertensive patients (n = 48, 0.174 ± 0.006 [mean ± SE]) than in normotensive subjects (n = 77, 0.140 ± 0.004). The coefficient increased in parallel with the patient’s age and with the grade of renal surface irregularity. In the patients whose serum creatinine levels were normal, this parameter also had a significant relationship (r = 0.367, P .0001) with serum creatinine. These results suggest that the heterogeneity of renal cortical circulation is increased in hypertension and is also associated with aging. This parameter may become a sensitive indicator to detect slight deterioration in the renal cortical circulation.

Ingestion of alcohol acutely decreases vascular resistance and blood pressure (BP) with activation of the sympathetic nervous system in Orientals. Although alpha1-blockers are widely used in the treatment of hypertension, the possible interaction between alcohol and alpha1-blockers has not been clarified. We examined the effects of prazosin on the alcohol-induced BP changes in Japanese men with mild hypertension. Ten hypertensive patients (54 +/- 3 years, mean +/- SE) were given 1 mL/kg of alcohol or isocaloric control drink with a light meal in the evening before and 5 to 7 days after treatment with prazosin (1 mg three times daily). Ambulatory BP monitoring was carried out every 30 min for 24 h in each period using Colin ABPM-630. Blood samples were obtained before and 2 h after intake of alcohol or control drink. Before prazosin treatment, alcohol ingestion decreased BP for several hours with a significant reduction in average 24-h BP, whereas it increased heart rate, plasma norepinephrine, and plasma renin activity. Treatment with prazosin caused a significant decrease in 24-h BP (136.3 +/- 4.0/82.8 +/- 2.5 v 131.6 +/- 3.2/80.0 +/- 2.3 mm Hg). The alcohol-induced hypotension at 2-4 h after ingestion was enhanced by prazosin (-18.0 +/- 3.7/-11.8 +/- 2.7 v -24.4 +/- 4.9/-17.8 +/- 2.8 mm Hg, P < .05 for diastolic BP). These results suggested that inhibition of the sympathetic nervous system with alpha1-blockers accentuates alcohol-induced hypotension. Ingestion of alcohol may cause a marked BP reduction in hypertensive Orientals treated with alpha1-blockers.

We report two cases with induced coronary spasm of the culprit lesion in the infarct related coronary artery in the chronic phase after primary percutaneous transluminal coronary angioplasty (PTCA). To our knowledge, there are few data on the response of the angioplasty site to ergonovine in human coronary arteries after primary PTCA. It is important to note that chest pain recurring after successful primary PTCA is not automatically related to restenosis, and coronary spasm in patients with previous myocardial infarction, should also be considered. (J Interven Cardiol 2000;31–34)

Previous studies suggested that stent area (SA) did not change after the Palmaz-Schatz stent implantation. Whether these findings apply to other types of stent, however, is unknown. This study assessed vascular response to stent implantation using intravascular ultrasound (IVUS) studies. Serial (pre-intervention to follow-up) IVUS imagings were used to study 57 native coronary lesions after the GFX stent or the Multilink stent implantation. The vessel area (VA) at lesion site increased at follow-up (16.92 +/- 3.67 mm(2) after intervention to 18.17 +/- 4.66 mm(2) at follow-up, P < 0.01). The SA also increased from 8.39 +/- 1.90 mm(2) after intervention to 8.80 +/- 2.08 mm(2) at follow-up (P = 0.02). Thirty-two percent of lesions showed late stent expansion. The stent expansion [Delta (after intervention to follow-up) SA] correlated significantly with the VA growth [Delta (after intervention to follow-up) VA] (r = 0.59, P < 0.0001). In conclusion, some lesions reveal late stent expansion after both the GFX stent and the Multilink stent implantation. Adaptive vessel remodeling may be followed by stent expansion.

Hepatocyte growth factor (HGF) is a multifunctional protein implicated in tissue regeneration, wound healing, and angiogenesis. We measured serum HGF concentrations in 37 patients with peripheral arterial occlusive disease (PAOD). Among them, 36 patients underwent arteriography. Serum HGF concentrations were also measured in 40 control subjects who remained free of vascular, liver, kidney, or lung disease. Patients with PAOD showed elevated serum HGF concentrations compared with control subjects (0.40+/-0.02 vs. 0.19+/-0.01 ng/mL; P0.001). Serum HGF concentrations were significantly higher in smokers compared with nonsmokers (0.45+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.003). The serum HGF concentrations in patients with collaterals tended to be higher than those in patients without collaterals (0.43+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.06). Moreover, in patients who underwent bypass surgery or angioplasty, serum HGF concentrations decreased from 0.41+/-0.03 to 0.21+/-0.04 ng/mL after treatment (P0.001). Serum HGF may be an useful marker for the diagnosis of PAOD. HGF may play an important role in angiogenesis and collateral vessel growth in PAOD.

Alcohol ingestion acutely lowers blood pressure (BP) with vasodilation and sympathetic activation in Oriental subjects. We examined the effects of beta blockade on cardiovascular and neurohumoral actions of alcohol in Japanese men with mild-to-moderate essential hypertension. Ten hypertensive patients (54+/-5 years, mean+/-SE) were given 1 ml/kg of alcohol or isocaloric control drink with a light meal in the evening before and 5-7 days after treatment with propranolol (20 mg three times daily). BP and heart rate (HR) were measured every 30 min for 24 h in each period. Blood sampling and echocardiographic examination were carried out before (17.00 h) and after (19.00 h) intake of alcohol or control drink, Before treatment, alcohol ingestion caused significant decreases in BP, total peripheral resistance and serum potassium concentration, while it increased heart rate (HR), cardiac output (CO), plasma norepinephrine and plasma renin activity (PRA). Treatment with propranolol significantly decreased BP and HR for 24 h. Propranolol and alcohol showed an additive depressor effect on night-time BP, and the alcohol-induced hypotension was similar before and after propranolol treatment. The alcohol-induced changes in HR, CO, PRA and serum potassium were significantly attenuated by propranolol. These results suggest that activation of the sympathetic nervous system plays a role in alcohol-induced cardiac stimulation, renin release and hypokalemia through beta receptors. Moderate doses of beta-blockers may not modify alcohol-induced BP reduction in Oriental subjects with hypertension.

The negative charges of dextran sulfate (DS) used for low-density lipoprotein (LDL) apheresis activate the intrinsic coagulation pathway, accompanied by the production of bradykinin. This study was undertaken to see whether cyclic nucleotide plasma levels are affected by DS LDL apheresis. Previously, we showed the rise in plasma levels of prostaglandins and nitric oxide derivatives accompanied by the rise in bradykinin levels. The physiologic effects of prostaglandins and nitric oxide become manifest through the intracellular signal of cyclic nucleotides. The plasma levels of the cyclic nucleotides (cyclic adenosine monophosphate [cAMP] and cyclic guanosine monophosphate [cGMP]) were examined when either of 2 anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. The plasma levels of cAMP during LDL apheresis using heparin were 9.2 +/- 0.3 (mean +/- SE) 12.4 +/- 0.6, 12.0 +/- 0.5, and 12.1 +/- 0.3 pmol/ml, respectively, at the 0, 1,000, 2,000, and 3,000 ml stages. The rise in cAMP levels was suppressed during apheresis using NM. There were no significant increases in cGMP during apheresis with heparin or with NM. There were significant negative correlations between changes in cAMP and those in the blood pressure. These findings suggest that bradykinin generated during apheresis exerts some physiologic effects via activation of the adenylate cyclase dependent pathway.

We report a 27-year-old Japanese man who developed acute renal failure associated with cold water immersion. The clinical course was consistent with that of acute renal failure attributable to acute tubular necrosis. A renal biopsy specimen showed patchy and focal loss of tubule cells, necrotic epithelium, interstitial edema, and arterial lumina obstructed by diffuse and severe intimal thickening. Endothelin increased more than five times in the early phase of the clinical course. Vasoconstriction and ischemia induced by cold exposure seem to lead to endothelin release. Endothelin may be related to the development of acute renal failure and intimal thickening.

To investigate the relationship between natriuretic peptides and left ventricular remodeling after acute myocardial infarction, left ventriculography and blood sampling were performed on admission, after 1 month and after 3 months in 33 patients with acute myocardial infarction (15 anterior and 18 inferior). Plasma atrial and brain natriuretic peptide concentrations at 1 and 3 months were higher than those of controls (P

1. Adrenomedullin, a newly identified vasorelaxant peptide, participates in the regulation of the cardiovascular system. To investigate the pathophysiological significance of adrenomedullin in patients with acute myocardial infarction, we measured plasma levels of adrenomedullin. 2. Cardiac catheterization was performed on admission, after 1 day, and after 4 weeks in 36 patients with acute myocardial infarction. We measured plasma levels of adrenomedullin, atrial natriuretic peptide and brain natriuretic peptide in the right atrium, pulmonary artery and aorta. 3. Plasma levels of adrenomedullin in the right atrium (mean ± SEM) were significantly increased on admission (4.2 ± 2.6 h) in patients with acute myocardial infarction (10.6 ± 1.0 pmol/l) compared with controls (5.2 ± 0.3 pmol/l, P < 0.01). In addition, plasma levels of adrenomedullin were further elevated in patients with congestive heart failure (12.3 ± 1.4 pmol/l) compared with patients without congestive heart failure (7.8 ± 0.6 pmol/l, P < 0.01). In patients with congestive heart failure, plasma adrenomedullin on admission significantly correlated with atrial natriuretic peptide and brain natriuretic peptide. 4. These results suggest that plasma adrenomedullin increases in the early phase of acute myocardial infarction and that volume expansion may be one of the additional stimuli for the release of adrenomedullin in patients with acute myocardial infarction complicated by congestive heart failure.

BACKGROUND The vasoreactivity after direct percutaneous transluminal coronary angioplasty (PTCA) in patients with previous myocardial infarction remains unknown. We examined the constrictor response to ergonovine of the infarct-related coronary artery in comparison with that of noninfarct-related coronary artery after angioplasty. METHODS Ergonovine was administered intravenously to 17 patients with previous myocardial infarction (group I) and to 21 patients with stable angina (group II) 1 year after PTCA. The effects of ergonovine on lumen diameter were analysed quantitatively at the PTCA segment, nonPTCA segment (proximal to the PTCA segment), and nonPTCA artery. RESULTS The ergonovine-induced decrease in minimal lumen diameter at the PTCA segment was significant in group I (decrease from 2.12 +/- 0.56 to 1.39 +/- 0.74 mm, P < 0.01), but not in group II (decrease from 1.60 +/- 0.35 to 1.43 +/- 0.33 mm, NS). Patients in group I showed a constrictor response at the nonPTCA artery (decrease in diameter from 2.54 +/- 0.90 to 1.94 +/- 0.77 mm, P < 0.01), and a tendency to constrict at the nonPTCA segment (2.56 +/- 0.67 to 2.11 +/- 0.66 mm, P = 0.06), whereas those in group II showed no significant constrictor response to ergonovine at any of the three segments examined. The changes in diameter at the three segments in patients in group I were significantly greater than those in group II (all P < 0.01). Subtotal coronary spasm at the PTCA segment was provoked only in three patients in group I (18%). CONCLUSIONS The constrictor response to ergonovine of the infarct-related coronary artery was enhanced compared with that of the noninfarct-related coronary artery. This difference in coronary vasoreactivity at the angioplasty segment may be due to previous hypersensitivity of the smooth muscle.

Antemortem diagnosis of hepatocellular carcinoma with a tumor thrombus extending into the right atrium has been rarely observed. Although echocardiography allows easy detection of the intracardiac mass, reports of echocardiographic descriptions of a right atrial mass associated with hepatocellular carcinoma are few. Herein, we describe two cases of hepatocellular carcinoma with a tumor thrombus in the right atrium detected by transthoracic echocardiography. In one of the patients we also performed transesophageal echocardiography. Neither patient had cardiac symptoms or signs. Thus, echocardiographic examination is very important in patients with hepatocellular carcinoma, with or without cardiac symptoms and signs.

The negative charges of dextran-sulfate (DS) used for low-density lipoprotein (LDL) apheresis activates the intrinsic coagulation pathway, in which plasma kallikrein acts on high-molecular-weight kininogen (HMWK) to produce large amounts of bradykinin. This study was undertaken to see whether bradykinin generated during DS LDL apheresis has some physiologic effects in vivo. The plasma levels of bradykinin and nitric oxide derivatives (NOx) were examined when either of 2 anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. Although anticoagulative action by NM depends on the inhibition of thrombin activity, this substance also inhibits the activity of plasma kallikrein. During apheresis using heparin, the marked increase in bradykinin levels (before apheresis, 18 +/- 3 (mean +/- SE, n = 5) pg/ml; after apheresis 470 +/- 140, p < 0.01) was associated with the increase in NOx (before apheresis 50 +/- 11 pg/ml; after apheresis 66 +/- 15). Interestingly, these changes in bradykinin and NOx levels were suppressed during apheresis using NM. The changes in plasma NOx levels were negatively correlated with those in blood pressures. These findings suggest that bradykinin generated during apheresis exerts some physiologic effects by means of activation of endothelium-derived relaxant factor (EDRF). Our results support the view that bradykinin produced during DS LDL apheresis has physiologic significance.

Low density lipoprotein (LDL) apheresis is at present one method of treatment in homozygous cases of familial hypercholesterolemia (FH). It is also effective in the prevention of the development of coronary atherosclerosis in patients with heterozygous FH and other types of mild hypercholesterolemia, leading to the regression of the stenosing lesions. In this paper, an overview is presented on the development of the devices for LDL apheresis and its short-and long-term effects on FH mainly based upon experience with the Liposorber system. LDL apheresis has served to protect the lives of patients from life threatening diseases like myocardial infarction although observations for more than 10 years in some laboratories have shown that the progression of atherosclerosis has taken place in many patients, and more importantly, the involvement of the aortic valve with calcification has developed. especially in patients who had homozygous FH, making this the most obstinate complication of FH. Therefore, more aggressive treatment or the combination of LDL apheresis with other therapies is required in the future. LDL apheresis has also been approved for the treatment of glomerulosclerosis and arteriosclerosis obliterans.

The purpose of this study was to clarify whether occlusal hypofunction and its recovery affect the structure of the periodontal ligament (PDL) and expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in rats. Forty-eight Wistar rats aged 5 weeks were used and randomly divided into three groups: the hypofunctional group (HG), recovery group (RG), and control group (CG). In HG and RG, appliances were attached to the maxillary and mandibular incisors. In HG, appliances were set for 11 weeks. In RG, appliances were set for 7 weeks. Appliances were then removed at 0, 1, 3, 7, 14, and 28 days. Untreated rats served as CG. Histological sections were prepared and immunohistochemically stained for VEGF and bFGF. Three groups were evaluated for PDL area and the number of VEGF and bFGF immunopositive cells in PDL. The number of immunopositive cells and PDL area in CG and RG were significantly larger when compared with HG, and PDL area in RG was similar to that in CG. In the recovery process, PDL area and number of VEGF-positive cells in PDL increased from days 0 to 7 and decreased from days 7 to 28. Conversely, the number of bFGF-positive cells in PDL increased significantly after day 1 and peaked at 28 days. This study suggests that occlusal stimuli regulate PDL area through expression of VEGF and bFGF in rat PDL. Occlusal stimuli are able to regulate the expression of VEGF and bFGF in PDL cells, and these growth factors may lead to alveolar bone remodeling in PDL.

Mesenchymal stem cells (MSCs) can be used for the regeneration of various tissues and cryopreservation of MSCs is so important for regenerative medicine. The purpose of this study was to evaluate the influences of cryopreservation on MSCs by use of a programmed freezer with a magnetic field (CAS freezer). MSCs were isolated from bone marrow of rat femora. The cells were frozen by a CAS freezer with 10% dimethyl sulfoxide (Me2SO) and cryopreserved for 7 days at a temperature of −150 °C. Immediately after thawing, the number of survived cells was counted. The cell proliferation also examined after 48 h culture. Next, MSCs were frozen by two different freezers; CAS freezer and a conventional programmed freezer without magnetic field. Then, osteogenic and adipogenic differentiations of cryopreserved cells were examined. As a result, survival and proliferation rates of MSCs were significantly higher in CAS freezer than in the non-magnetic freezer. Alizarin positive reaction, large amount of calcium quantification, and greater alkaline phosphatase activity were shown in both the non-cryopreserved and CAS groups after osteogenic differentiation. Moreover, Oil Red O staining positive reaction and high amount of PPARγ and FABP4 mRNAs were shown in both the non-cryopreserved and CAS groups after adipogenic differentiation. From these findings, it is shown that a CAS freezer can maintain high survival and proliferation rates of MSCs and maintain both adipogenic and osteogenic differentiation abilities. It is thus concluded that CAS freezer is available for cryopreservation of MSCs, which can be applied to various tissue regeneration.

Dextran-sulfate (DS) cellulose used for low-density lipoprotein (LDL) apheresis seems to be a weak activator of the contact phase of the intrinsic coagulation pathway because the surface of this substance has negative charges. Heparin, a commonly used anticoagulant, has no effect on this process whereas the process is inhibited by a newly developed anticoagulant, nafamostat mesilate (NM). The effects on bradykinin generation were compared between heparin and NM. Five patients with severe hypercholesterolemia were treated with LDL apheresis using either heparin or NM on a different day. During apheresis with heparin, factor XII, high molecular weight kininogen, and prekallikrein were markedly decreased by passing through the DS column. A distinct generation of bradykinin was observed by passing plasma through the DS column, and this led to the rise of bradykinin levels from 12 +/- 5 (mean +/- SE) to 72 +/- 14 pg/ml after treatment of 1,000 ml of plasma. NM suppressed almost completely the rise of bradykinin levels. Although blood pressure was apt to decrease during apheresis with heparin, there was no significant difference in blood pressure between heparin and NM. Since an angiotensin-converting enzyme inhibitor may lead to a marked rise in blood levels of bradykinin by suppressing its degradation, the use of NM is recommended for apheresis in patients taking this drug.

著者人数: 11名, 資料番号: SA1160200000

Primary cardiac lymphoma, which is very rare, is generally regarded to have a poor prognosis. A case of a 69-year-old man with primary cardiac lymphoma diagnosed by antemortem exam ination is reported. A computed tomography scan of the chest demonstrated a huge right atrial mass with invasion into the other chambers. No mediastinal lymphadenopathy was detected. Cytologic analysis of pericardial effusion revealed diffuse large B-cell type non- Hodgkin malignant lymphoma. The patient died on the 18th day of chemotherapy (cyclophos phamide, hydroxydaunomycin, oncovin, and prednisone) due to low-output syndrome and multiple organ failure. At autopsy, massive gray-white tumor almost occupied the right atrium and invaded the right inferior lobe of the lung. Although prognosis of primary cardiac lymphoma remains poor, early diagnosis may improve the prognosis.

薬物治療に抵抗する狭心症を合併した維持血液透析中の12例 (男8, 女4例, 平均年齢は56.3歳) に対する経皮的冠動脈形成術 (PTCA) の治療成績について検討した. 合計27狭窄病変に対してPTCAを施行し, 22狭窄病変 (82%) の拡張に成功した. 不成功例は2例で, そのうちの1例は小脳出血により死亡したが, 他の11例では重篤な合併症は出現しなかった. 患者成功は12例中10例 (83%) で, 非透析例と同等の治療成績であった. 11例の平均追跡期間は2年5か月で, 狭心症が4例に再発し, 3例には再度PTCAを施行し, 全例成功した. 透析患者に対する冠動脈バイパス術はいまだにhigh riskとされていることから, 透析患者の難治性狭心症に対しては, 解剖学的に禁忌・不適応でない限り, PTCAが第一選択と考えられた.

Introduction The purpose of this study was to examine the effect of a new cryopreservation method with a magnetic field on periodontal regeneration in vitro and in vivo. Methods Human periodontal ligament cells were frozen in 10% dimethyl sulfoxide by using a programmed freezer with a magnetic field. Cells were cryopreserved for 3 days at −150°C. Immediately after thawing, collagen type I and alkaline phosphatase gene expression were determined by real-time polymerase chain reaction. Incisors were extracted from 15-week-old Wistar rats and cryopreserved or dried for 3 days. Then the incisors were replanted into the same sockets. Ninety days after transplantation, they were observed under light microscopy. Results There was no difference in the messenger RNA expression of collagen type I between the cryopreserved and the control groups. The expression of alkaline phosphatase messenger RNA in the cryopreserved group was slightly decreased compared with the control group. There was no progressive root resorption in the teeth that were replanted immediately (control group) or cryopreserved. However, there was widespread root resorption and ankylosis in the dried teeth. Conclusions These results show that a magnetic field programmed freezer can be successfully used for cryopreservation of teeth.

The purpose of this study was to evaluate the effects of long-term cryopreservation on the isolated human periodontal ligament cells (PDL) and pulp tissues. In the first part of study, 10 freshly extracted teeth were selected and divided into two groups. In the cryopreserved group, the teeth were frozen for 5 years using a programmed freezer combined with a magnetic field, known as Cells Alive System "CAS". As for the control group, freshly extracted teeth were used. In each group, extracted PDL tissues were cultured and gene expression and protein concentration of collagen type I, alkaline-phosphatase (ALP) and vascular endothelial growth factor (VEGF) was compared between the two groups. In the second part, pulp tissues were obtained from 10 mature and immature third molars which were freshly extracted or cryopreserved for three months. Expression of VEGF and nerve growth factor (NGF) mRNAs and the protein concentration in the supernatant were investigated. Results indicated that long-term cryopreservation with the use of CAS freezer cannot affect the growth rate and characteristics of PDL cells. There was no significant difference in VEGF expression and VEGF and NGF protein concentration of pulp cells derived from cryopreserved teeth with immature apex and control group with mature root formation. Finally, proper PDL regeneration and appropriate apexogenesis after transplanting magnetically cryopreserved immature tooth was clinically confirmed. These findings demonstrate that teeth banking with the use of magnetic field programmed freezer can be available for future autotransplantation as a treatment modality for replacing missing teeth.

1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16-18 g/day) and after 7 days of a low salt intake (1-3 g/day). 2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na+ concentration: 147.7 +/- 0.4 mmol/L vs 145.3 +/- 0.5 mmol/L; P less than 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period. 3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt-sensitive (n = 8) and the non-salt-sensitive (n = 7) subjects, but the changes in plasma NA and PRA were smaller in the salt-sensitive subjects. 4. These results indicate that the sympathetic nervous system is less suppressed in salt-sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system.

We assessed the effect of stopping smoking on future cardiac events (cardiac death and non-fatal myocardial infarction (MI)) in 90 male smokers with previous MI by a prospective follow-up study. At the time of enrollment, the patients were divided into 2 groups according to their current smoking status (Group A: those who had stopped smoking (n = 60), and Group B: those who were still smoking (n = 30)). Follow-up was performed prospectively by annual postal questionnaires. During the mean follow-up period of 3.1 +/- 1.4 years, 13 cardiac events (11 cardiac deaths and 2 cases of non-fatal MI) occurred in the 87 evaluable patients. The cardiac event rates in Groups A and B were 8.5% and 28.6%, respectively, and the relative risk was 3.4 (Group A vs B, p less than 0.05) by univariate analysis. The relative risk using multivariate analysis (Cox) was also statistically significant (3.1, p less than 0.05). HDL-cholesterol was significantly lower in Group B than in Group A, but other coronary risk factors apart from smoking were not significantly different between the two groups. At the end of the follow-up period, 89.8% of the patients in Group A remained nonsmokers and 21% of the patients in Group B had stopped smoking.Stopping smoking significantly reduced the risk of future cardiac events in male smokers with previous MI. This prospective follow-up study demonstrated that a significant reduction in the risk of future cardiac events could be achieved by stopping smoking in this group of patients.

This study was performed to elucidate the effect of a hypocaloric diet on blood pressure and sodium balance in overweight women with essential hypertension. Hospitalized patients were fed a hypocaloric diet (900 kcal/day) for 3 weeks after being fed a standard diet (SD) for more than 2 weeks. During the study, the sodium and potassium intake was kept constant as was the level of exercise activity. After the mean arterial pressure (MAP) and body weight had stabilized during the last week on the SD, caloric restriction significantly reduced the body weight by 1.5kg in the first week and by 0.8-0.9 kg in subsequent weeks, and reduced the MAP by 5mmHg and by 1-3mmHg, respectively. Although caloric restriction reduced the excretion of urinary norepinephrine and C-peptide, and elevated the serum levels of ketone bodies that would induce natriuresis, the urinary sodium excretion remained unchanged, indicating that sodium balance was unchanged even by caloric restriction. These results suggest that caloric restriction lowers the blood pressure in a short time with no significant change in sodium balance. (Hypertens Res 1992; 15: 137-142)

The mechanism of polyuria associated with paroxysmal supraventricular tachycardia (SVT) was investigated in 8 patients. SVT was induced artificially and sustained for 60 minutes. Urine and blood samples were collected every 30 minutes. During the latter half of SVT, urine flow increased twofold in the control subjects before SVT. Urinary sodium excretion increased significantly (p less than 0.01) within 30 minutes after SVT. Urinary excretion of antidiuretic hormone (ADH) decreased (p less than 0.01) during the latter half of SVT and increased (p less than 0.01) after SVT, respectively. Plasma level of ADH did not change during SVT but increased (p less than 0.05) after SVT. The concentration of plasma atrial natriuretic polypeptide (ANP) increased significantly (p less than 0.05) before SVT ended. Urinary excretion of prostaglandin E2 increased significantly (p less than 0.05) after termination of SVT. The percent changes in the urinary excretion of prostaglandin E2 were correlated (r = 0.713, p less than 0.001) with those of ADH. There was also a correlation (r = 0.6, p less than 0.001) between the percent changes in the urinary excretion of prostaglandin E2 and those of sodium. Their findings suggest that the polyuria during SVT is attributed mainly to the inhibition of ADH release and that the natriuresis after SVT is due not only to the increased ANP but also to the increased renal prostaglandin E2 probably stimulated by ADH.

近年, 透析患者の循環器疾患による死亡率は年々増加してきている. そこで, 透析患者の予後を決定する上で, 血圧がどの程度関与しているか検討した. 1977年から1987年までに当施設で血液透析に導入し, 転院し得た慢性腎不全患者195例 (男123例, 女72例, 平均年齢54±1歳) について導入期および, 維持期 (転院時) における血圧と1990年1月現在における生死との関連を検討した. 3年以上生存した生存群132例と3年未満に死亡した死亡群46例との比較では, 死亡群で平均年齢が高く (61±2歳vs 50±1歳), 糖尿病性腎症の割合が高く, 収縮期血圧は導入期 (178±4mmHg vs 167±2mmHg), 維持期 (165±4mmHg vs 147±2mmHg) とも高値であった. ただし, 拡張期血圧に関しては導入期, 維持期とも両群間に有意差を認めなかった. 非糖尿病性腎症例に限ると維持期収縮期血圧のみ死亡群で有意に高値であった. そこで, 維持期収縮期血圧に着目し160mmHg以上をHT群, 160mmHg未満をNT群とし, 累積生存率を比較検討した. 195例全例でも, 非糖尿病性腎症でも, 糖尿病性腎症例でもHT群に比しNT群で有意に生存率が高値を示した. 導入期から維持期に至る収縮期血圧の推移別に, 1. 導入期収縮期血圧が160mmHg以上であったが, 維持期には160mmHg未満に低下したHT-NT群, 2. 維持期にもなお160mmHg以上を示したHT-HT群, および3. 導入期, 維持期を通して160mmHg未満であったNT-NT群の3群に分類し累積生存率を比較した. HT-NT群はHT-HT群に比し有意に生存率が高くNT-NT群と有意差のないレベルに達していた. 以上より, 透析導入によって是正された後の維持期収縮期血圧が透析患者の予後を決定する重要な因子と考えられた.