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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 433 records · Page 24Linked to original sources

[Cardiac contractile dysfunction in response to surgical stress including trauma, hemorrhage, and infection].

Shock and multiple organ failure are complications of primary conditions such as trauma, hemorrhage and infection. Ample evidence of cardiac contractile dysfunction has been obtained in both septic patients and experimental animal models of endotoxin shock. Recent advance in molecular biology and immunology has improved our understanding of the pathogenesis of septic shock, and thus, it is now believed that the host's inflammatory response to infection contributes to the development of septic shock. In addition, effects of toxic host mediators including cytokines, kinins, eicosanoids, platelet-activating factor, and nitric oxide, which are produced by activated cells, on cardiovascular system have been examined. The possible involvement of the nitric oxide pathway, not only as a marker for cytokine-induced effects on myocyte gene expression, but also as a mediator for cytokine-induced contractile dysfunction, was explored. According to this hypothesis, trauma and hemorrhage, both of which lead to host's inflammatory response, is also considered to induce contractile dysfunction. In this paper we reviewed the influences of various shock states on cardiac contractility. Hemorrhagic and burn shocks possibly depress cardiac contractility as well as septic and endotoxin shocks. Therefore, it is necessary to improve contractile depression in the diseased states to meet oxygen demand of each patient under monitoring patient's circulatory and metabolic conditions.

Animals↗

Afferent projections to the Bötzinger complex from the upper cervical cord and other respiratory related structures in the brainstem in cats: retrograde WGA-HRP tracing.

Following injection of WGA-HRP (30-60 nl, 5%) into the Bötzinger complex (Böt.c), a group of expiratory neurons in the vicinity of the retrofacial nucleus, a number of labeled neurons were observed, predominantly ipsilaterally, in the intermediate zone of the upper cervical cord at the C1 and C2 segments, the retrotrapezoid nucleus (RTN) in the ventrolateral medulla and the parabrachial-Kölliker-Fuse nuclear complex in the rostral pons. In addition, clusters of labeled cells were also observed in and around the solitary tract nucleus, nuclei ambiguus and retroambiguus, and nucleus raphe magnus. Control injections into the magnocellular tegmental field adjacent to the Böt.c resulted in a diffuse distribution of labeled neurons in the reticular formation. These results demonstrate that the Böt.c receives convergent monosynaptic axonal projections from the upper cervical spinal cord, the pontine pneumotaxic area, the RTN and several other respiratory related structures in the medulla.

Afferent Pathways↗

Expression of local hepatocyte growth factor system in vascular tissues.

Since endothelial cells (EC) are known to secrete various anti-proliferative and vasodilating factors, an agent that promotes seeding or regeneration of EC may have potential therapeutic value against vascular smooth muscle cell (VSMC) proliferation. For the above purpose, we have found that hepatocyte growth factor (HGF) fulfills such conditions. However, the local HGF system has not yet clarified. Therefore, we investigated endogenous HGF production and its specific receptor (c-met) in vascular tissues. Our results revealed the expressions of HGF and its receptor (c-met) mRNA in endothelial cells, VSMC and neointimal VSMC of rat assessed by RT-PCR. HGF and c-met mRNA were also detected in human aortic endothelial cells and VSMC. Endothelial cells and VSMC of both rat and human produce and secrete immunoreactive HGF as assessed by ELISA. Of importance, the existence of local HGF system (HGF and c-met) was also observed in vivo in intact abdominal aorta of SD and Wistar rats. Overall, this study demonstrated that HGF is expressed and secreted from endothelial cells and VSMC of both rat and human in vitro as well as in vivo. Since HGF has characteristics of an endothelium-specific growth factor, locally synthesized HGF in endothelial cells and VSMC may have a role in vascular functions in autocrine-paracrine manner.

Animals↗

Early immunohistochemical changes of microtubule based motor proteins in gerbil hippocampus after transient ischemia.

Changes of immunoreactivities for microtubule based motor proteins, kinesin and cytoplasmic dynein, and non-motor protein, microtubule associated protein (MAP) 2 were investigated in gerbil hippocampus after transient ischemia. The immunoreactivities for kinesin showed a progressive decrease in hippocampal CA1 cells from 8 h after transient 5 or 15 min of ischemia that is lethal to the CA1 cells, while it showed no change after 2 min of ischemia that is non-lethal to the cells. The immunoreactivities for cytoplasmic dynein showed a decrease from 3 or 1 h of reperfusion in the CA1 cells after 5 or 15 min of ischemia, respectively. In contrast, the immunoreactivity for MAP2 remained normal until 2 days in the CA1 cells after 5 min of ischemia. These results showed an early changes of microtubule based motor proteins, such as kinesin and cytoplasmic dynein in vulnerable CA1 neurons. These changes may affect the mitochondrial shuttle system between neuronal cell body and the peripheries such as axon terminal and dendrites. This early disturbance may cause a failure to obtain newly synthesized nuclear encoded mitochondrial protein, and result in mitochondrial dysfunctions and the subsequent cell death.

Animals↗

Variance of age at onset in a Japanese family with amyotrophic lateral sclerosis associated with a novel Cu/Zn superoxide dismutase mutation.

Although about 5 to 10% of amyotrophic lateral sclerosis (ALS) cases are familial, the pathophysiology of ALS remains unknown. A new point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD) gene, resulting in an amino acid substitution of leucine84 by valine (L84V), in a Japanese patient with familial ALS (FALS) was identified. This L84V substitution was not observed in 57 normal Japanese control subjects. The enzymatic activities of Cu/Zn SOD of skin fibroblasts were significantly reduced to 75% of the control level in the affected patient. The progression of the disease with this mutation is very rapid, but the age at onset varies with sex or generation within a family.

Adult↗

Expansion of circulating gamma delta T cells in active sarcoidosis closely correlates with defects in cellular immunity.

The relationship between the level of gamma delta T cells and cellular immunity of T lymphocytes was assessed in the peripheral blood of active sarcoidosis patients and healthy controls. We divided the active sarcoidosis patients into two groups: a group of patients with a normal distribution of circulating gamma delta T cells (group A; n = 11, less than 8.2% lymphocytes) and another group with increased gamma delta T cell levels (group B; n = 11, greater than 8.2% lymphocytes). The proportion and absolute count of CD4+ lymphocytes in group B (28.6 +/- 11.2%, 374.1 +/- 193.8/microliters) were remarkably smaller than control subjects (45.7 +/- 6.8%, 818.3 +/- 290.2/microliters, P < 0.001, P < 0.002, respectively). Group A, however, showed a moderate reduction in CD4+ lymphocytes when compared with controls. Serial measurements of T cell subtypes were performed on five patients in group B. gamma delta T cells and CD4+ lymphocytes were inversely correlated over the observation period which ranged from 2 to 18 months. When peripheral blood T cells were stimulated with PHA or PPD in vitro, the responses were weaker in group B compared with both group A and control subjects. These results suggest that the increase in circulating gamma delta T cells in sarcoidosis closely relates to a defect in cellular immunity which progresses during the disease process.

Adult↗

Monosynaptic rubrospinal projections to distal forelimb motoneurons in the cat.

In the present electrophysiological experiments, we examined whether or not there are short-latency excitatory postsynaptic potentials (EPSPs) suggesting monosynaptic rubro- and corticomotoneuronal connections in the cervical spinal segments in cats. Under pentobarbital anesthesia and immobilization with gallamine triethiodide, intracellular recordings were made from forelimb motoneurons (Mns) following stimulation of the red nucleus (RN) and the cerebral peduncle (CP). Mns comprising the musculocutaneous nerve (Musc. Mns), the radial nerve (Rad. Mns), the ulnar nerve (Uln. Mns), and the median nerve (Med. Mns) were identified by their antidromic activation. Single-pulse stimulation of RN produced EPSPs with a mean amplitude of 0.35 mV in the majority of forelimb Mns (88 of 122, 72%). Half of the forelimb Mns (23 of 46) of the C8-T1 segments in which RN-EPSPs were detected by single shocks exhibited segmental latencies of RN-EPSPs shorter than 1.0 ms, while only 3 of 43 (7%) forelimb Mns in the C6-7 segments showed such latencies. These results suggest that rubromotoneuronal connections are, at least in part, monosynaptic for forelimb Mns that innervate in particular the hand and digit muscles. When paired-pulse stimuli (interpulse interval of 3 ms) were applied to RN, the second EPSPs were potentiated moderately (mean amount of temporal facilitation 24%) for EPSPs with short segmental latencies (< 1.0 ms). By contrast, single shocks to CP rarely produced EPSPs in forelimb Mns (9 of 106, 8%). There was no obvious evidence to suggest monosynaptic connections between corticospinal fibers and the forelimb Mns. The present results suggest the presence of preferential direct rubrospinal projection to Mns innervating distal forelimb muscles in the cat.

Animals↗

Phylogenetic relationships of some Microsporum and Arthroderma species inferred from mitochondrial DNA analysis.

Thirty-eight strains of 12 Microsporum and 10 Arthroderma (Nannizzia) species were investigated by analysis of mitochondrial DNA with 6 restriction enzymes, and classified into 13 genetic groups. The phylogenetic tree of the 13 groups thus established was constructed. On the tree, M. audouinii, M. langeronii, M. rivalieri, M. distortum, M. equinum, M. ferrugineum and A. otae comprise one genetic group and are suggested to be the same species. A. gypseum, A. fulvum, M. duboisii, M. ripariae, A. incurvatum, A. persicolor and A. obtusum are clustered on one of five boughs of the tree indicating their close relation. A. racemosum and A. cajetani are also closely related.

Ascomycota↗

Surgical management of tricuspid malinsertion in the Rastelli operation: conal flap method.

From June 1986 to May 1994, 25 patients underwent the Rastelli operation for complete transposition of the great arteries with ventricular septal defect and pulmonary stenosis or atresia. Fourteen patients whose tricuspid valve chordae were normal underwent the conventional Rastelli procedure (conventional group), whereas 11 patients who had tricuspid malinsertion into the infundibular septum underwent the Rastelli operation concomitant with mobilization of the infundibular septal flap, with the tricuspid valve chordae, to the right ventricular side of the intraventricular conduit (conal flap method) (conal flap group). In relation to the mobilization of the tricuspid valve chordae, right heart function and tricuspid regurgitation were compared between the two groups. There was one early death after the conventional Rastelli procedure and no early death after the Rastelli operation with a conal flap. There was one late death in the conventional group and two late deaths in the conal flap group. The mean follow-up was 50.8 +/- 5.1 months in the conventional group and 54.9 +/- 7.5 months in the conal flap group (p = 0.43). Reoperation was necessary for 1 patient in the conal flap group during follow-up. At the most recent follow-up, all patients in both groups were in New York Heart Association functional class I. Tricuspid regurgitation was estimated from the echocardiograms. Mild to moderate regurgitation was noted in 6 patients in the conventional group and 8 in the conal flap group. However, postoperative right heart catheterization data did not show any significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Multiple↗

pH strategies and cerebral energetics before and after circulatory arrest.

The pH-stat strategy compared with the alpha-stat strategy provides more rapid recovery of brain high-energy phosphate stores and intracellular pH after 1 hour of hypothermic circulatory arrest in pigs. Possible mechanisms for this difference are (1) improved oxygen delivery and homogeneity of brain cooling before deep hypothermic circulatory arrest and (2) greater cerebral blood flow and reduced reperfusion injury owing to extracellular acidosis during the rewarming phase. To identify which of these mechanisms is predominant, we studied 49 4-week-old piglets undergoing 1 hour of deep hypothermic circulatory arrest. Four groups were defined according to cooling/rewarming strategy: alpha/alpha, alpha/pH, pH/alpha, and pH/pH. In 24 animals cerebral high-energy phosphate levels and intracellular pH were measured by magnetic resonance spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 5). In 25 animals cerebral blood flow was measured by labeled microspheres, cerebral metabolic rate by oxygen and glucose extraction, and the redox state of cytochrome aa3 and hemoglobin oxygenation by near infrared spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 6). Cerebral blood flow was greater with pH-stat than alpha-stat during cooling (56.3% +/- 3.7% versus 32.9% +/- 2.1% of normothermic baseline values, p < 0.001). Cytochrome aa3 values became more reduced during cooling with alpha-stat than with pH-stat (p = 0.049). Recovery of adenosine triphosphate levels in the initial 45 minutes of reperfusion was more rapid in group pH/pH compared with that in the other groups (p = 0.029). Recovery of cerebral intracellular pH in the initial 30 minutes was faster in group pH/pH compared with that in group alpha/alpha (p = 0.026). Intracellular pH became more acidic during early reperfusion only in group alpha/alpha, whereas it showed continuous recovery in the other groups. This study suggests that there are mechanisms in effect during both the cooling and rewarming phases before and after deep hypothermic circulatory arrest that could contribute to an improved cerebral outcome with pH-stat relative to more alkaline strategies.

Adenosine Triphosphate↗

Effect of suture knots on tensile strength of repaired canine flexor tendons.

59 dog cadaver flexor digitorum profundus tendons were repaired with one or two knots inside or outside the tendon, using two, four and six suture strands. The ultimate tensile strength and gap strengths were compared. Locating the knots outside rather than within the tendon repair site showed significantly higher ultimate tensile strength for two, four, and six strand sutures. The strength was greater in one knot than in two knot sutures; the value of the six-strand suture using the one knot outside technique was the greatest. Similarly, increased gap strength was also obtained from the one-knot-outside technique. We concluded that the knots should be located away from the tendon repair site and there should be as few as possible.

Animals↗

Work of flexion after tendon repair with various suture methods. A human cadaveric study.

After flexor tendon repair there is often increased resistance to tendon gliding at the repair site, which is greater for techniques using increased suture strands or suture material. This increased "friction" may be measured as the "work of flexion" in the laboratory setting. Tendon repairs performed in zone 2 in human cadaver hands using the two strand Kessler, the lateral Becker, the six strand Savage, internal and dorsal tendon splint, or the external mesh sleeve techniques, had "work of flexion" measurements made both before and after the laceration and repair. The average increase in work of flexion was 4.8% for Kessler; 6.5% for Becker; 10.9% for Savage; 19.3% for the internal tendon splint, 16.2% for the dorsal tendon splint and 44.3% for the external mesh sleeve. The work of flexion was found to increase in direct proportion to the amount of suture material at the repair site.

Biomechanical Phenomena↗

Treatment of Pancoast tumors. Combined irradiation and radical resection.

Eighteen patients underwent combined preoperative irradiation and radical resection for a Pancoast tumor at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1977 and 1993. Four patients were applied a full radiation dose of 50-70 Gy and fourteen patients were applied a reduced dose of 33-40 Gy preoperatively. Eleven of these fourteen were applied a supplemental dose postoperatively up to a total dose of at least 50 Gy. Fourteen lobectomies, three partial resections, and one pneumonectomy were performed with combined resection of chest wall or adjacent structures: rib in 14, vertebra in 4, brachiocephalic vein in 3, subclavian artery in 2, spinal nerve in 3, sympathetic truncus in 2, phrenic nerve in 2 cases. Chest walls were reconstructed with marlex mesh in 5 patients, and two subclavian arteries and one brachiocephalic vein were repaired with artificial grafts. In 13 patients complete resections were achieved, but in the other 5 only incomplete resections leaving residual tumor were achieved. Incomplete resections consisted of 4 positive stumps at the brachial plexus of the apex and one aortic involvement by a metastatic lymph node. There was one operative death. Median survival was 21.6 months and the 5-year-survival rate was 38.5% for all 18 patients. In the complete resection group 5-year-survival was 56.4%, but in the incomplete-resection group 0%, showing a significantly more favorable result for the complete resection group. It is considered that evidence of incomplete resection influences the prognosis and that particularly tumor invasion to the brachial plexus may serve as a limiting factor for surgery.

Adult↗