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Altered expression and functional responses to cardiac beta(3)-adrenergic receptors (ARs) may contribute to progressive cardiac dysfunction in heart failure (CHF). We compared myocyte beta(3)-AR mRNA and protein levels and myocyte contractile, [Ca(2+)](i) transient, and Ca(2+) current (I(Ca,L)) responses to BRL-37344 (BRL, 10(-8) mol/L), a selective beta(3)-AR agonist, in 9 instrumented dogs before and after pacing-induced CHF. Myocytes were isolated from left ventricular myocardium biopsy tissues. Using reverse transcription-polymerase chain reaction, we detected beta(3)-AR mRNA from myocyte total RNA in each animal. Using a cloned canine beta(3)-AR cDNA probe and myocyte poly A(+) RNA, we detected a single band about 3.4 kb in normal and CHF myocytes. beta(3)-AR protein was detected by Western blot. beta(3)-AR mRNA and protein levels were significantly greater in CHF myocytes than in normal myocytes. Importantly, these changes were associated with enhanced beta(3)-AR-mediated negative modulation on myocyte contractile response and [Ca(2+)](i) regulation. Compared with normal myocytes, CHF myocytes had much greater decreases in the velocity of shortening and relengthening with BRL accompanied by larger reductions in the peak systolic [Ca(2+)](i) transient and I(Ca,L). These responses were not modified by pretreating myocytes with metoprolol (a beta(1)-AR antagonist) or nadolol (a beta(1)- and beta(2)-AR antagonist), but were nearly prevented by bupranolol or L-748,337 (beta(3)-AR antagonists). We conclude that in dogs with pacing-induced CHF, beta(3)-AR gene expression and protein levels are upregulated, and the functional response to beta(3)-AR stimulation is increased. This may contribute to progression of cardiac dysfunction in CHF.

The beta2-adrenergic receptor (beta2-AR)-mediated increase in cardiac L-type Ca2+ current (I(Ca,L)) has been documented in normal subjects. However, the role and mechanism of beta2-AR activation on I(Ca,L) in heart failure (HF) are unclear. Accordingly, we compared the effect of zinterol (ZIN), a highly selective beta2-AR agonist, on I(Ca,L) in isolated left ventricular cardiomyocytes obtained from normal control and age-matched rats with HF induced by left coronary artery ligation (4 months). I(Ca,L) was measured by using the whole-cell voltage-clamp technique. In normal myocytes, superfusion of ZIN (10(-5) M) caused a 21% increase in I(Ca,L) (9.21 +/- 0.24 versus 7.59 +/- 0.20 pA/pF) (p < 0.05). In HF myocytes, the same concentration of ZIN produced a significantly greater increase (30%) in I(Ca,L) (6.20 +/- 0.24 versus 4.75 +/- 0.17 pA/pF) (p < 0.01). This ZIN-induced increase in I(Ca,L) was further augmented in both normal and HF myocytes (normal: 59 versus 21%; HF: 71 versus 30%) after the incubation of myocytes with pertussis toxin (PTX, 2 microg/ml, 36 degrees C, 6 h). These effects were not modified by the incubation of myocytes with CGP-20712A (3 x 10(-7) M), a beta1-AR antagonist, but were abolished by pretreatment of myocytes with ICI-118551 (10(-7) M), a beta2-AR antagonist. In addition, all of the effects induced by ZIN were completely prevented in the presence of an inhibitory cAMP analog, Rp-cAMPS (100 microM, in the patch-pipette solution). In conclusion, beta2-AR activation stimulates L-type Ca2+ channels and increases I(Ca,L) in both normal and HF myocytes. In HF, beta2-AR activation-induced augmentation of I(Ca,L) was increased. These effects are likely to be mediated through a cAMP-dependent mechanism and coupled with both stimulatory G protein and PTX-sensitive G protein.

In the present study, film cooling characteristics by the jets through various easy-to-make straight holes and slots have been investigated. In this experiment, seven kinds of injection geometries were used. They were circular, rectangular, elliptic and oval holes and slots, respectively.

The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) dynamics before and after pacing-induced CHF at rest and during Ex in nine conscious, instrumented dogs. Before CHF, there were modest increases in circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance was enhanced during Ex with decreases in the time constant of LV relaxation (tau), LV end-systolic volume (V(ES)), and LV minimum pressure with a downward shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This produced an increase in peak LV filling rate without an increase in mean left atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were elevated and increased to very high levels during Ex. After CHF, mean LA pressure, tau, and LV minimum pressure were elevated at rest and increased further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or losartan, an ANG II AT(1)-receptor blocker, decreased these abnormal Ex responses in CHF more effectively than an equally vasodilatory dose of sodium nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers was more effective than either agent alone. We conclude that in CHF, circulating ANG II and ET-1 increase to very high levels during Ex and exacerbate the diastolic dysfunction present at rest.

Background: Superoxide (O(2)(-)) generated by enhanced xanthine oxidase (XO) activity may contribute to the increased myocardial oxidative stress in heart failure (CHF). Because blocking XO with allopurinol augments myofilament Ca(2+) sensitivity in reperfusion injury and CHF, we hypothesized that it may improve adrenergic inotropic responsiveness in CHF., Methods and Results: We studied the effect of allopurinol on the contractile response to dobutamine and exercise in 7 chronically instrumented conscious dogs before and after producing CHF by rapid pacing. Left ventricular (LV) contractile performance was measured by the slopes of the LV end-systolic pressure-volume relation (E(ES)) and stroke work-end-diastolic volume relation (M(SW)). Before CHF, allopurinol produced no change in LV contractile performance and did not alter the response to dobutamine or exercise. After CHF, allopurinol produced significant (P:<0.05) increases in E(ES) (5.0+/-0.6 versus 3.3+/-0.6 mm Hg/mL) and M(SW). Dobutamine and allopurinol produced greater increases in E(ES) (5.4+/-0.6 versus 7.4+/-0.6 mm Hg/mL) and M(SW) (60.1+/-7.4 versus 73.7+/-4.4 mm Hg) than did dobutamine alone. After allopurinol, dP/dt(max), stroke volume, and M(SW) were higher during CHF exercise. LV diastolic pressures were lower during CHF exercise after allopurinol., Conclusions: Allopurinol has no discernable effects on LV contractile function or adrenergic responsiveness in normal, conscious animals. In pacing-induced CHF, however, allopurinol improves LV systolic function at rest and during adrenergic stimulation and exercise.

Different types of periodontopathic bacterial lipopolysaccharide (LPS) exert various biological activities in vitro. However, whether or not these activities also occur in vivo remains unclear. Thus the present study investigates bone resorption, as well as local IL-1alpha and IL-1beta synthesis induced by Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis LPS in the periodontal tissue of mice. Both types of LPS were injected into mouse gingiva every 48 h and the animals were sacrificed 6 h after the 1st. 4th, 7th, 10th, 13th, 16th, 20th, or 24th injection. Bone resorption in the injected gingiva was histopathologically and histomorphometrically investigated and local concentrations of IL-1alpha and IL-1beta were detected using an enzyme-linked immunosorbent assay. The active resorption ratio was significantly higher in the group given the 10th injection of LPS from A. actinomycetemcomitans than in the group given P. gingivalis LPS. Furthermore, A. actinomycetemcomitans LPS stimulated significantly more synthesis of IL-1alpha than P. gingivalis LPS after the 4th and 10th injections. and of IL-1beta after the 4th, 7th, 10th, 13th, 16th and 20th injections. These results suggest that A. actinomycetemcomitans LPS is a more potent inducer of bone resorption and synthesis of IL-1alpha and IL-1beta in the short term than P. gingivalis LPS.

Whether periodontal ligament (PDL) tissue is capable of inducing root resorption was examined. The distal root of the rat molar was sectioned at the furcation and the PDL tissue removed from the root (non-PDL group, n=40). The distal root with the PDL intact was also prepared (PDL-intact group, n=40). The roots were transplanted into the dorsal skin of the rat. On the 1st, 3rd, 5th, 7th, 10th, 14th, 21st or 28th day after transplantation, the roots were removed together with surrounding dorsal subcutaneous tissue and were fixed, demineralized and embedded in paraffin. Serial sections from each block were stained with haematoxylin and eosin or by the tartrate-resistant acid phosphatase (TRAP) method to observe root-resorbing cell formation. Cyclo-oxygenase-2 (COX2) was also detected immunohistologically to examine prostaglandin E(2) production. On the 7th day after transplantation, multinucleated root-resorbing cells with TRAP were observed in the PDL-intact group. The number of TRAP-positive cells peaked on the 10th day after transplantation. COX2-positive cells were observed in PDL during the early experimental stages. No root resorption was seen in the non-PDL group. These results suggest that PDL tissue is involved in the formation of root-resorbing cells and root resorption.

Introduction: The discussions in this theme provided an opportunity to address the unique hazards facing the Pacific Rim., Methods: Details of the methods used are provided in the preceding paper. The chairs moderated all presentations and produced a summary that was presented to an assembly of all of the delegates. Since the findings from the Theme 3 and Theme 7 groups were similar, the chairs of both groups presided over one workshop that resulted in the generation of a set of action plans that then were reported to the collective group of all delegates., Results: The main points developed during the presentations and discussion included: (1) communication, (2) coordination, (3) advance planning and risk assessment, and (4) resources and knowledge., Discussion: Action plans were summarized in the following ideas: (1) plan disaster responses including the different types, identification of hazards, focusing training based on experiences, and provision of public education; (2) improve coordination and control; (3) maintain communications, assuming infrastructure breakdown; (4) maximize mitigation through standardized evaluations, the creation of a legal framework, and recognition of advocacy and public participation; and (5) provide resources and knowledge through access to existing therapies, the media, and increasing and decentralizing hospital inventories., Conclusions: The problems in the Asia-Pacific rim are little different from those encountered elsewhere in the world. They should be addressed in common with the rest of the world.

Objectives: The right heart function of the patients with pulmonary atresia and intact ventricular septum was assessed periodically during the process of staged biventricular repair, and the implications for its long-term outcome were analyzed., Subjects and Methods: During the period from 1971 to 1990, 21 neonates or infants with pulmonary atresia and intact ventricular septum had undergone initial palliative surgery. There were seven early postoperative deaths and one late death. Of the 13 survivors, 10 patients underwent subsequent biventricular repair and form the basis of this study. Their clinical records of roentgenography, electrocardiography, and catheterization studies at each staged period were reviewed retrospectively., Results: Arrhythmia occurred late in 2 patients, one of whom died by arrhythmia at 11 years after definitive surgical repair. Therefore the actuarial survival rate was 85.7% at 14 years. The catheterization study after the definitive biventricular repair revealed a significant fall in the right heart pressure (p = 0.0005) and significant improvement in the right ventricular ejection fraction (p = 0.0004). In angiocardiography, dilatation of the right atrium was noted in all patients and was more marked in those who developed arrhythmia in conjunction with rapid growth of the right ventricle. Moreover, the serial repeated electrocardiography disclosed progressive and significant prolongation of both PQ interval (p = 0.003) and QRS duration (p = 0.021)., Conclusions: Although biventricular repair for pulmonary atresia and intact ventricular septum proved to attain a satisfactory long-term result, it failed to resolve right heart dysfunction. Postoperative arrhythmia was prone to precipitate progressive dilatation of the right atrium.

Purpose: For successful organ transplantation, it is important to properly preserve the donor organ. This study was carried out to investigate tissue damage generated by the activation of calpain during prolonged hypothermic cardiac preservation using specific antibodies for mu- and m-calpain proenzymes, and to ensure the protective effect of calpain inhibitor 1 (N-acetyl-leucyl-leucyl-norleucinal)., Methods: Excised rat hearts were divided into two groups: in Group I, the heart was arrested and immersed in University of Wisconsin solution with 20 microM of calpain inhibitor 1 (n = 28) and in Group N, the heart was arrested and immersed in University of Wisconsin solution without calpain inhibitor (n = 27). After a 12-hour preservation period at 4 degrees C, the hearts were reperfused on an isolated perfusion apparatus. Separation of the myocardial calpain isozymes was carried out by DEAE cellulose chromatography and both calpain proenzymes were detected by immunoblotting., Results: The cardiac function was more satisfactorily maintained in Group I in comparison with Group N. Remarkable leakage of creatine kinase, glutamic-oxaloacetic transaminase and lactate dehydrogenase was detected in Group N, while it was efficiently suppressed in Group I. During ischemia, mu-calpain proenzyme decreased in Group N (p < 0.01), but there was no significant change in m-calpain. However, during reperfusion, both mu- and m-calpains decreased more in Group N (p < 0.01)., Conclusion: Activation of calpain proenzymes and a decrease in cardiac function during preservation and reperfusion were demonstrated. The use of calpain inhibitor to protect against tissue damage was suggested as being useful for the prolonged preservation of the heart.

A case of Salmonella subdural empyema developed in chronic subdural hematoma (Infected Subdural Hematoma; ISH) was reported. A 64-year-old man had been in a nearby hospital due to myelodysplastic syndrome with cerebral infarction for two months. His condition there had been almost uneventful. But spike fever occurred and the patient became drowsy two days before his transfer to our medical center. His consciousness level deteriorated progressively and CT scan showed a right chronic subdural hematoma. He had had no history of head trauma in the previous two months. On admission to our center, his consciousness level was semicoma with anisocoria. An emergency operation was performed via a single burr hole initially. From the burr hole, old bloody fluid accompanied by yellowish pus was obtained. Thus so-called ISH was diagnosed and the craniotomy was carried out. Gram stain of the specimen revealed gram negative rods. Although an epileptic state developed after the operation, it was controlled by barbiturate coma therapy for 3 days, followed by phenytoin administration. Fever subsided gradually with antibiotics sensitive to the bacteria and his anisocoria disappeared on the 4th postoperative day. In this case, Salmonella enteritidis was detected from bacterial culture both of the specimen and of the arterial blood. Salmonella enteritidis might have been implanted on the capsule of the chronic subdural hematoma by bacteremia derived from immunological dysfunction due to myelodysplastic syndrome. In conclusion, the possibility of ISH should be considered in chronic subdural hematoma patients with immunological dysfunction.

The purpose of this study was to clarify the involvement of CD4+ and CD8+ T cells on bone resorption induced by Escherichia coli endotoxin. Two kinds of monoclonal antibodies, anti-CD4 and/or anti-CD8, were employed for the depletion of each or both T cell subsets. E. coli endotoxin was injected into mouse mesial gingiva of the first molar of the left mandible every 48 hours for up to 14 days (7 injections). The mice were divided into four groups: CD4-depleted, CD8-depleted, T cell-depleted, and normal. The mice were sacrificed on the day after the 1st, 3rd, 4th, 5th, and 7th injection and alveolar bone was examined histopathologically and histomorphometrically. Bone surface in contact with osteoclasts was defined as the site of active resorption and the ratios of active resorption were compared among the four groups. In addition, sections obtained after the 1st, 4th, and 7th injection were immunohistologically stained in order to confirm the presence or absence of CD4+ or CD8+ T cells. Alveolar bone resorption gradually increased in normal mice as the number of injections increased. In contrast, alveolar bone resorption was significantly weaker in each or both subset-depleted mice. For the duration of the experimental period, the number of CD4+ T cells in CD8-depleted and normal mice significantly increased with increasing bone resorption. Considering the function of CD4+ and CD8+ T cells, these results suggest that each subset preferentially acts as a macrophage activator in the early period of bone resorption induced by E. coli endotoxin.

We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized into class I and II depending on the methine length, were synthesized and evaluated as a novel antitumor agent. Attention was particularly focused on the structure-activity study of two heteroaromatic rings. In class I, where the A rings were conjugated to rhodanine via two methine groups, compounds 1, 20, 23, and 24 were found to be efficacious in tumor-bearing nude mice model study, but they did not have the chemical properties (stability, solubility) suitable for clinical use. In contrast, in class II, where the A rings were directly conjugated to rhodanine, compounds 13 and 25, which possessed a benzothiazole moiety for the A ring, exhibited the favorable biological and chemical properties. Therefore, we decided to have a benzothiazole moiety as the A ring and introduce various heterocyclic groups for the B ring. As a result, the pyridinium ring was selected as the optimal moiety for the B ring (compound 13). Further, the variation of counteranion had a profound effect on solubility in water without influence on antitumor activity. Chloride anion was selected as the favorable anion with respect to synthetic method as well as solubility in water. Our study finally led us to the identification of compound 3 (MKT 077, 1-ethyl-2-[[3-ethyl-5-(methylbenzothiazolin-2-ylidene)-4-oxothi azolidin-2 -ylidene]methyl]pyridinium chloride) as the candidate for clinical trials and is currently subjected to further investigation as a potent antitumor agent in phase I clinical trial for the treatment of solid tumors.

Rhodacyanine dyes and several analogous delocalized lipophilic cations (DLCs) were synthesized and evaluated as novel antitumor agents. Rhodacyanine dye consists of two heteroaromatic rings such as thiazoles at both termini of the conjugate systems and 4-oxothiazolidine (rhodanine) in the middle of it. Compounds with such a unique double-conjugate structure were found to inhibit the growth of several tumor cell lines, such as colon carcinoma CX-1, and to exhibit relatively low toxicity against normal kidney cell line CV-1 (e.g., IC50(CX-1) = 50 nM, IC50(CV-1) = 17.3 microM; selectivity index = 346 for compound 5). These compounds were also found to be efficacious in the tumor-bearing nude mice model (e.g., against human melanoma LOX; T/C (%) = 168 for compound 5). Structural modifications on rhodacyanine, including deletion of a heteroaromatic ring involved in the merocyanine conjugate system and replacement of rhodanine with a structurally related moiety such as 4-oxoimidazolidine or 4-oxo-1,3-dithiolane, resulted in a loss of the selectivity and/or the activity. Our current structure-activity studies imply that the double-conjugate system with a rhodanine moiety is essential for the selective activity of rhodacyanine dyes, and we find this class of compounds as unique antitumor agents candidates.

One of the world's largest port cities, Kobe and its vicinity, was hit by a so-called "shallow and direct hit" type earthquake with a magnitude of 7.2 on the Richter scale in the early morning of January 17, 1995. A total of 6308 people were killed and approximately 35,000 people were injured. About 400,000 houses and buildings were more or less damaged, and electricity, water, and city gas supply were suspended in a wide area. Medical facilities were also greatly damaged. The destruction of roads, highways, bridges, and railways made it difficult for people to move within this area. Extraordinary traffic congestion occurred. Telephone lines were disconnected or overloaded. Thus, the modern healthy urban lives that the people had taken for granted were lost in a moment. Emergency responses to the disaster fell behind. Transportation of severely injured patients away from the disaster area to the non-affected area was not smooth because of the interruption of communications and traffic congestion. The scope of the damage from the disaster, types of injuries, characteristics of the victims, problems with emergency medical care encountered in this disaster, and revisions of countermeasures executed after the disaster are reported.

At least 372 people developed crush syndrome after they were injured by the Great Hanshin-Awaji Earthquake. Of these, 23 were transferred to Osaka City General Hospital from the disaster area. The serum creatinine kinase (CK) of each of the 23 patients exceeded 10,000 IU/L. Sixteen of these patients were treated with various methods of blood purification including hemodialysis (HD), plasma exchange (PE), and continuous hemodiafiltration (CHDF). The effectiveness on each method of blood purification was evaluated in this study based on the clearance of myoglobin and the length of time until recovery from acute renal failure (ARF). None of the patients died, and none suffered from ARF longer than 2 months. The length of time required for blood purification was significantly correlated with the serum CK and myoglobin levels on admission. The serum myoglobin levels decreased linearly regardless of the method of blood purification used. Our findings showed that the severity of ARF that occurred in association with crush injury was proportional to the amount of crushed muscle and that once ARF had developed, the clearance of myoglobin was not affected by any of the blood purification methods tested including HD, PE, and CHDF. Therefore, the method of blood purification employed for crush syndrome should be selected for its effectiveness in treating ARF, rather than the elimination of myoglobin.

Objective: The wall shear stress generated by blood flow regulates the expression of fibrinolytic proteins by endothelial cells in vitro. In the present study, the effects of pulmonary blood flow on fibrinolytic activity were studied in patients with congenital heart defects and pulmonary hypertension., Methods: Twenty-seven patients who underwent cardiac operation because of congenital heart defects were divided into four groups according to the severity of pulmonary hypertension. Group I consisted of seven patients with normal pulmonary artery pressure, group II consisted of nine patients with pulmonary hypertension caused by increased pulmonary blood flow, group III consisted of six patients with pulmonary hypertension caused by increased pulmonary vascular resistance, and group IV consisted of five patients with tetralogy of Fallot. Plasma concentrations of tissue plasminogen activator, plasmin, and thrombin were assayed as the inhibitor-bound forms., Results: The preoperative concentration of tissue plasminogen activator was higher in group II than in all other groups (p = 0.0003). However, the postoperative concentration decreased only in patients in group II when compared with the preoperative value (p = 0.01). By Pearson's correlation analysis, pulmonary blood flow was found to correlate with the preoperative concentration of tissue plasminogen activator (95% confidence interval = 3.99 to 10.58, p = 0.0001). No definite conclusion was found for the relationship between tissue plasminogen activator and plasmin concentration. Further, the preoperative thrombin concentration was similar in all groups., Conclusions: These findings suggest that pulmonary blood flow may regulate the plasma concentration of tissue plasminogen activator in patients with congenital heart defects.

This paper presents a constitutive law of the lumbar intervertebral disc to be described mathematically with the finite deformation theory. Mechanical behavior of the cadaveric lumbar disc obtained from continuous cyclic compression-tension tests and continuous cyclic axial torsion tests was formulated by the constitutive equation with a semi-circular shaped model. These equations were formulated with or without taking the nucleus pulposus into account. It was also confirmed that forward-backward bending behavior of the disc could be simulated numerically from these equations.

Michael addition of cytosine, N4-dimethyl-aminomethylidene-cytosine, uracil and thymine to the nitroolefin (2) generated in situ from 1-(4,6-O-benzylidene-3-deoxy-3-nitro-beta-D-glucopyranosyl)-uracil (1) gave the corresponding 2-(N1-pyrimidinyl)-2,3-dideoxy-3-nitro-beta-D-glucopyranosides (3-6). Compound 3 was also obtainable from 4.

Using the method of reconstitution of nude mice with T cells, we examined the effects of T cell on alveolar bone resorption induced by repeated injections of Escherichia coli endotoxin into periodontal tissue. Three mice groups (normal, nude and T cell reconstituted nude mice) were used. Endotoxin derived from E coli was repeatedly injected into the gingiva of the mice left mandibles every 48 h and the mice were killed on the day after the 1st, 4th, 7th, 10th, 13th and 20th injections of endotoxin. Alveolar bone resorption was examined histopathologically and histomorphometrically. Bone surfaces in contact with the osteoclast were defined as the site of active resorption and the ratios of active resorption were compared among the 3 mice groups. Consequently, no active resorption was found after the first injection of endotoxin in any group. After the 4th injection, active resorption was found in normal mice and T cell reconstituted nude mice and gradually rose with the increase in the injection frequency. In contrast, few osteoclasts were found even after the 10th injection in the nude mice. In addition, there were statistically significant differences between the normal mice and nude mice after the 4th and 10th injections (p < 0.05). These findings suggested that T cell influences periodontal bone destruction induced by local administration of endotoxin during the early phases.

Study Design: The lumbar and lumbosacral segmental motions were analyzed in vivo using cineradiographic method., Objectives: To reveal the in vivo motion behavior of the lumbar and lumbosacral segments and their contribution to the whole lumbar motion., Summary of Background Data: Relation between the lumbar motion and hip joint motion has been well investigated. The lumbar motion preceded the hip flexion in forward bending and delayed from extension of the hip joints in backward bending. However, it remains unclear how the lumbar and lumbosacral segmental motion contributed to the whole lumbar motion in vivo., Methods: Eight healthy male subjects participated in this study. The lower lumbar and lumbosacral motion (L3-S1) was recorded using cineradiography during flexion and extension. Each trunk motion was carried out from the neutral position to the maximum position. Segmental rotation and translation were measured sequentially at the L3-L4, L4-L5, and L5-S1 motion segments., Results: Intersegmental motion lags were observed between the lumbar and lumbosacral motion segments during flexion. The lower lumbar and lumbosacral motion (L3-S1) was initiated at the L3-L4 motion segment. The L4-L5 segmental motion delayed from the L3-L4 motion by an average of 6 degrees and preceded the L5-S1 motion by an average of 8 degrees. In extension, motions in the L3-L4 and L4-L5 segments were small, and the L5-S1 segmental motion only contributed to the total lower lumbar motion., Conclusions: The lumbar and lumbosacral segmental motions occurred not simultaneously but stepwise from the upper level with intersegmental motion lags during flexion. These intersegmental motion lags were much larger than the neutral zone in vitro, which implied the neutral zone in vivo should be different from the neutral zone in vitro.

Three-dimensional configuration of the scoliotic spine was mathematically expressed by a spatial curve passing through each vertebral centroid ("vertebral body line"). Three-dimensional location of the vertebral centroid was determined from digitization on the frontal and sagittal roentgenograms. Cobb angle, which is clinically used for measuring scoliosis curvature, was calculated in space to evaluate scoliosis deformity three-dimensionally. In forty-five scoliotic spines, regardless of curvature and curve patterns, the spinal configurations were excellently approximated by vertebral body lines. Vertebral body lines swerved from the sagittal plane at the end vertebrae, but aligned on a certain plane within the scoliosis region. Three-dimensional Cobb angle, which was larger than that in the frontal plane, can be utilized to evaluate the scoliosis deformity.

Study Design: Local elastic moduli of sliced intervertebral disc specimens were studied after establishing the relation between the elastic modulus and indentation behaviors by model tests using polyurethane specimens., Objectives: This study presents a method to quantify the distribution of compressive elastic moduli in the lumbar intervertebral disc and to clarify the effects of degeneration on the distribution., Summary of Background Data: No study has been performed to evaluate the distribution of axial compressive elastic moduli, which is supposed to relate previous biomechanical, biological, and biochemical findings regarding the intervertebral disc., Methods: Local compressive elastic moduli of the intervertebral disc were estimated by indentation tests. To evaluate the distribution of elastic moduli, indentation tests were performed at nodal points of a 10 mm x 10 mm network on a specimen. Nine cadaveric lumbar discs (L3-L4 and L4-L5) with various degrees of degeneration were tested. The age of subjects ranged 39 to 90 years (mean, 58.4 years)., Results: The distribution of elastic moduli in normal discs was symmetric about the midsagittal plane. The mean elastic modulus in the nucleus pulposus was 5.8 kPa and those of the anterior and posterior anulus fibrosus were 110.7 and 75.8 kPa, respectively. The elastic moduli in the lateral portions were the lowest in the normal anulus, and were close to the values of the nucleus. Compared to normal discs, degenerated discs showed irregular distributions of elastic moduli. The elastic moduli of the degenerated nucleus were higher than those in normal discs., Conclusions: The distribution of elastic moduli is much different between discs with and without degeneration.

MKT-077 (formerly known as FJ-776) is a newly synthesized, highly water-soluble ( > 200 mg/ml) rhodacyanine dye that exhibits significant antitumor activity in a variety of model systems. In culture, MKT-077 inhibits the growth of five human cancer cell lines (colon carcinoma CX-1, breast carcinoma MCF-7, pancreatic carcinoma (CRL 1420, bladder transitional cell carcinoma EJ, and melanoma LOX) but not monkey kidney CV-1, an indicator cell line for normal epithelial cells. In nude mice, MKT-077 inhibits the growth of s.c. implanted human renal carcinoma A498 and human prostate carcinoma DU145 and prolongs the survival of mice bearing i.p. implanted human melanoma LOX (tumor:control = 344%). Subcellular localization indicates that MKT-077 is taken up and retained by mitochondria, and flow cytometric analysis suggests that CX-1 cells take up MKT-077 to a much greater extent than CV-1 cells. Quantitation of MKT-077 uptake by ethanol extraction shows that CX-1 cells accumulate 65-fold more MKT-077 than do CV-1 cells. MKT-077 is the first delocalized lipophilic cation with a favorable pharmacological and toxicological profile in preclinical studies. MKT-077 is now being investigated in Phase I clinical trials.

Five cases of ASD-PDA complex were experienced. The incidence of ASD-PDA complex was 1.2% of CHD in our institution. The age at operation was ranged from 10 days after birth to 2 years of age. Four patient were male and 1 was female. Also, 4 patients had noncardiac anomalies, including Down syndrome, microcephaly, cleft palate, micrognathia, and cranioschisis. All patient had moderate or severe pulmonary hypertension. Three patients received ASD and DA closure under cardiopulmonary bypass, however, 2 patients were succeeded in decreasing CTR and pulmonary vascular shadow by ligation of DA. Operative and hospital mortality was none. We also studied concerning clinical features and surgical treatment by the review of 38 cases reported in Japan and our 5 cases.

To reveal deformation behaviour of normal lumbar discs (L((3/4)), L((4/5)) andL(5)/S(1), the lumbar spines of eight asymptomatic volunteers were examined cineradiographically during flexion and extension of the trunk. Disc deformation could be evaluated by displacement of the superior corners of the disc, which were measured with respect to the upper surface of the adjacent lower vertebra. Furthermore the in-vivo strain distribution of each lumbar disc was analysed by the finite element method and in-vivo measurement of the disc deformation. During flexion, deformation of the lumbar disc increased rapidly after a certain delay from the start of trunk motion and reached maximum value before the finish of trunk motion. It was also confirmed that time lags were present between the onsets of disc deformation. Namely, each disc deformed not simultaneously but stepwise from the upper to the lower level with time lags during flexion. When the lower disc deformation started, the strain at the adjacent upper discs had already reached more than half of the value at full flexion. RELEVANCE: The present study revealed one of the phenomena of lumbar spinal kinematics, which will provide helpful information to clinical problems such as evaluation of spinal instability.

Purpose: To investigate the adequacy of hospital disaster preparedness in the Osaka, Japan area., Methods: Questionnaires were constructed to elicit information from hospital administrators, pharmacists, and safety personnel about self-sufficiency in electrical, gas, water, food, and medical supplies in the event of a disaster. Questionnaires were mailed to 553 hospitals., Results: A total of 265 were completed and returned (Recovery rate; 48%). Of the respondents, 16% of hospitals that returned the completed surveys had an external disaster plan, 93% did not have back-up plans to accept casualties during a disaster if all beds were occupied, 8% had drugs and 6% had medical supplies stockpiled for disasters. In 78% of hospitals, independent electric power generating plants had been installed. However, despite a high proportion of power-plant equipment available, 57% of hospitals responding estimated that emergency power generation would not exceed six hours due to a shortage of reserve fuel. Of the hospitals responding, 71% had reserve water supply, 15% of hospitals responding had stockpiles of food for emergency use, and 83% reported that it would be impossible to provide meals for patients and staff with no main gas supply., Conclusions: No hospitals fulfilled the criteria for adequate disaster preparedness based on the categories queried. Areas of greatest concern requiring improvement were: 1) lack of an external disaster plan; and 2) self-sufficiency in back-up energy, water, and food supply. It is recommended that hospitals in Japan be required to develop plans for emergency operations in case of an external disaster. This should be linked with hospital accreditation as is done for internal disaster plans.

The function of the blood-nerve barrier appears quite unique in the nerve root. Protein tracers that were injected into the subarachnoid space passed through the nerve root sheath and entered into the capillary lumen in the endoneurial space but tracers that were injected intravenously did not appear in the endoneurial space. Marked extravasation of protein tracers in the nerve root was induced at the compressed part by strong compression (60 gram force, 30 gram force) and capillaries in the nerve root showed opening of the tight junction accompanied by an increase in vesicular transport under the electron microscope. This situation was reflected as high intensity on Gadolinium-enhanced magnetic resonance imaging. In twenty-one of fifty patients with lumbar disc herniation, the affected nerve root was strongly enhanced by Gadolinium-diethylene-triaminepentaacetic acid, indicating that the blood-nerve barrier in the affected nerve root was broken and intraradicular edema was produced in these cases.

A method for selecting the individually suitable form and location of major connectors for partially edentulous patients is described. Light-polymerized resin patterns are alternately placed in the patient's mouth, and the most suitable location and the form of the major connector are selected. This trial pattern method makes it possible to better address the problems posed by difficult removable partial denture patients.

A method for making directly a single solid vectorcardiogram is reported. A solid vectorcardiogram was made by employing an apparatus for production of three-dimensional objects by stereolithography. Stereolithography is a computer-aided manufacturing technique that is practiced in conjunction with computer-aided design and engineering. To design the solid vectorcardiogram, voltages in the X, Y and Z axes obtained according to the Frank lead are memorized in the computer-aided design system. By use of the stereolithography apparatus, the designed solid vectorcardiogram is formed in a vat filled with liquid plastic. In the vat, the plastic changes rapidly from liquid to solid in the presence of ultraviolet light so that a solid vectorcardiogram made of solid plastic may be formed.

Hemolysis does not necessarily result in acute renal failure in severely burned patients, but free serum hemoglobin may play some important role in the development of renal damage. This controlled study of the effects of haptoglobin administration in severely burned patients presenting with hemoglobinuria produced the following results: As long as free hemoglobin was present in the plasma, free serum haptoglobin remained undetectable. Free serum hemoglobin dropped rapidly after haptoglobin treatment, whereas the free serum hemoglobin levels in control patients remained unchanged for at least 12 hours. The time required for macroscopic hemoglobinuria to clear showed a statistically significant difference between the haptoglobin-treated patients and the control patients. Some patients among the haptoglobin-treated group had prolonged hemolysis and hemoglobinuria which might have cleared with additional doses of haptoglobin.

Pancreatic secretory trypsin inhibitor (PSTI) in serum was measured periodically in 15 patients with serious abdominal and non-abdominal injuries. From the second or third posttraumatic day, serum PSTI began to rise. Elevation of serum PSTI to more than twice the initial value was seen in 93% of the patients following serious injury. In uneventful cases, it declined and returned to the level at the time of admission within 14 days, but in the patients with serious inflammations and in the patient who died, it remained elevated. The change in the concentration of serum PSTI was significantly correlated with those of the acute phase reactants (fibrinogen and alpha 1-antitrypsin). There was no correlation between the level of serum PSTI and serum amylase activity or creatinine.

Twenty-six of 31 seriously injured patients (84%) showed a marked elevation of serum pancreatic secretory trypsin inhibitor (PSTI) to more than twice the initial level within the first 2 weeks after admission. Serum PSTI rose from the second or third post-traumatic day and reached the maximum at day 5.8 on average. In uneventful cases, it returned to the level on admission within 2 weeks. The maximum serum PSTI in these patients was significantly correlated with the severity of the injury as judged at the time of admission, indicating that the elevation of serum PSTI in these patients was related to the extent of initial damage. In contrast, serum PSTI in patients with serious complications remained at high level even at 2 weeks after trauma, and it was not correlated with the initial severity of the injury.