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Biomedical subjects

T Adachi

Publications and source records attributed to T Adachi.

At least 145 records · Page 8Linked to original sources

Dexmedetomidine reduces seizure threshold during enflurane anaesthesia in cats.

Dexmedetomidine is an alpha 2 agonist and has been reported to have proconvulsant actions. To investigate the interaction of dexmedetomidine with convulsant anaesthetics, we studied effects on seizure threshold in cats during enflurane anaesthesia. Cats were prepared with chronic implantation of electrodes for recording of the cortical electroencephalogram (EEG) and midbrain reticular formation multi-unit activity (R-MUA). Seizure threshold, the reciprocal of the number of electrical stimuli required to induce generalized EEG seizure activity x 1000 (seizure induction index (SII)), was assessed. The effects of dexmedetomidine 1, 10 and 100 micrograms kg-1 i.v. and yohimbine 500 micrograms kg-1, an alpha 2 antagonist, on SII during 3.5% enflurane anaesthesia were investigated. Dexmedetomidine significantly increased SII at 10 and 100 micrograms kg-1, and this effect was reversed by yohimbine. We found that high-dose dexmedetomidine reduced seizure threshold during enflurane anaesthesia.

Adrenergic alpha-Agonists↗

Living related donor liver transplantation in a patient with severe aortic stenosis.

We report the successful anaesthetic management of a young girl with Alagille's syndrome and severe aortic stenosis (resting pressure gradient 88 mm Hg) undergoing living related donor liver transplantation (LRDLT). The patient had end-stage liver disease and LRDLT was performed before replacement of the aortic valve. Anaesthesia was conducted uneventfully with the aid of a pulmonary artery catheter. Intra-aortic balloon pumping was used in the perioperative period for protection against myocardial ischaemia. Total clamping of the inferior vena cava was avoided during surgery and volume administration was guided by the pulmonary artery pressure. A stable circulation was maintained in the reperfusion period. The patient was discharged from hospital on day 54 after operation with normal liver function. Two years later her aortic valve was replaced successfully.

Alagille Syndrome↗

Xenon has greater inhibitory effects on spinal dorsal horn neurons than nitrous oxide in spinal cord transected cats.

UNLABELLED: Xenon (Xe) suppresses wide dynamic range neurons in cat spinal cord to a similar extent as nitrous oxide (N2O). The antinociceptive action of N2O involves the descending inhibitory system. To clarify whether the descending inhibitory system is also involved in the antinociceptive action of Xe, we compared the effects of Xe on the spinal cord dorsal horn neurons with those of N2O in spinal cord-transected cats anesthetized with alpha-chloralose and urethane. We investigated the change of wide dynamic range neuron responses to touch and pinch by both anesthetics. Seventy percent Xe significantly suppressed both touch- and pinch-evoked responses in all 12 neurons. In contrast, 70% N2O did not show significant suppression in touch- and pinch-evoked responses. These results suggest that the antinociceptive action of Xe might not be mediated by the descending inhibitory system, but instead may be produced by the direct effect on spinal dorsal horn neurons. IMPLICATIONS: Xenon (Xe) is an inert gas with anesthetic properties. We examined the antinociceptive effects of Xe and nitrous oxide (N2O) in spinal cord-transected cats. Our studies indicate that Xe has a direct antinociceptive action on the spinal cord that is greater than that of N2O.

Anesthetics, Inhalation↗

Clonidine inhibits and phorbol acetate activates glutamate release from rat spinal synaptoneurosomes.

UNLABELLED: Glutamate is a major neural transmitter of noxious stimulation in the spinal cord. We measured glutamate release from rat spinal synaptoneurosomes by using an enzyme-linked fluorimetric assay. Glutamate was released from spinal cord synaptoneurosomes in response to the addition of 30 mM potassium chloride, 1 mM 4-aminopyridine, or 1 microM ionomycin in the presence of external calcium. There was less release of glutamate in the absence, versus the presence, of external calcium. Clonidine significantly reduced the level of glutamate released from the spinal cord synaptoneurosomes. Tetradecanoyl phorbol acetate, an activator of protein kinase C, enhanced glutamate release. Forskolin, a protein kinase A activator, had no effect on the glutamate efflux. Our data indicate that glutamate released in the spinal cord is dependent on protein kinase C but is independent of the protein kinase A pathway. They also suggest that the inhibition of glutamate release may be the underlying mechanism of antinociception by clonidine at the spinal cord level. IMPLICATIONS: We demonstrated that synaptoneurosomes from rat spinal cord could release glutamate in response to depolarization. We showed that an activator of protein kinase C increased glutamate released from spinal cord synaptoneurosomes but that clonidine decreased it. Glutamate release may be one of the mechanisms of antinociception at the spinal cord level.

4-Aminopyridine↗

ATIII-independence of anticoagulant effect of human urinary soluble thrombomodulin.

We investigated antithrombin III (ATIII)-dependency of the anticoagulant effects of human urinary soluble thrombomodulin (UTM) both in vivo and in vitro, in comparison with those of heparins. For neutralization of rat plasma ATIII activity, we used F(ab')2 fragment of anti-rat ATIII antibody and could establish an appropriate in vivo model to evaluate the ATIII-dependency of antithrombotic agents. The efficacy of UTM on thromboplastin-induced disseminated intravascular coagulation produced in ATIII-decreased rats was almost the same as that in normal rats, whereas unfractionated (UF)-heparin remarkably diminished its effect in ATIII-decreased rats. The prolongation effect of UTM on activated partial thromboplastin time or prothrombin time in plasma in vitro was unchanged in both normal and ATIII-decreased rats, but the effect of UF-heparin remarkably diminished in ATIII-decreased rat plasma. Such ATIII-independence in the anticoagulant effect of UTM was also observed in human plasma. Thus, differing from heparins, since the anticoagulant effect of UTM does not depend on plasma ATIII activity, UTM is expected to be a useful antithrombotic agent for the treatment of thromboembolic diseases, even in the case with low plasma ATIII activity.

Animals↗

Perinatal and infant outcome of pregnant patients undergoing chronic hemodialysis.

Recently, perinatal outcome in patients undergoing chronic hemodialysis has been improved. But the conditions that will most likely result in successful pregnancy are still obscure. We retrospectively analyzed 15 pregnant patients who were undergoing chronic hemodialysis before pregnancy treated in our perinatal center. We divided these 15 cases into 2 groups: one group of 11 patients whose infants survived and the other group of 4 patients whose infants died 6 h to 8 months after birth due to prematurity. The rate of successful pregnancies having a surviving infant was 73.3% (11/15). We compared the maternal conditions and the progress of pregnancy in the 2 groups. Significant differences (p<0.01) were seen as follows. The patients in the group whose infants survived underwent hemodialysis for a shorter term before pregnancy (1-6 years), most of them (9/11) could produce urine (> or =50 ml/day), and the period of gestation was extended (33.3+/-4.7 weeks), so the infants were heavier (1,782.9+/-678.3 g). All the patients who underwent more than 9 years of hemodialysis could not have a surviving infant. From this we can assume that the shorter the period of dialysis before pregnancy, the better the condition is that is likely to result in women giving birth and the better is their infant's chance of survival.

Adult↗

The association between Trp64Arg polymorphism of the beta3-adrenergic receptor and autonomic nervous system activity.

The beta3-adrenergic receptor plays a significant role in the control of lipolysis and thermogenesis in brown adipose tissue through autonomic nervous system (ANS) activity. As the Trp64Arg polymorphism of the beta3-adrenergic receptor gene might affect ANS activity, we investigated the association of the polymorphism with ANS activity. The prevalence of the polymorphism was determined in 204 subjects. Ten normal homozygous, 10 heterozygous, and 1 variant homozygous subjects were examined for ANS activity during supine rest and standing by electrocardiogram R-R interval power spectral analysis. Subjects with the variant did not differ from subjects without the variant in body mass index, plasma glucose, plasma insulin, or family history of diabetes or obesity. The total power of heterozygotes at supine rest was lower than that of normal subjects (1124.6 +/- 191.6 vs. 3029.8 +/- 758.8 ms2; mean +/- SE). With a postural change to standing, the parasympathetic and sympathetic nervous system activity indexes of heterozygotes showed a higher response than those of normal subjects (parasympathetic nervous system index, 0.10 +/- 0.02 vs. 0.17 +/- 0.02; sympathetic nervous system index, 10.55 +/- 1.47 vs. 6.26 +/- 1.09), and the difference in total power disappeared. These findings show that subjects with the variant, even the heterozygotes, had lower resting ANS activity than normal subjects.

Adult↗

Isolation of two novel alternative splicing variants of allograft inflammatory factor-1.

Allograft inflammatory factor-1 (AIF-1) was initially cloned from rat cardiac allografts undergoing chronic rejection. AIF-1, possessing an EF-hand-like motif, is thought to be a Ca2+ binding protein. In this study, we identified two novel alternatively spliced variants of AIF-1 by reverse-transcription polymerase chain reaction. One variant encodes an AIF-1 protein that lacks 14 amino acids corresponding to one exon. The other variant encodes a truncated AIF-1 protein due to a frameshift introduced by an 85-bp insertion, and its C-terminal region differs from that of AIF-1. Interestingly, these variants have incomplete and no EF-handlike motifs, respectively. The expression level of the latter variant is high in peripheral blood leukocytes, and it is selectively expressed in macrophage-like cell lines.

Alternative Splicing↗

Involvement of galectin-3 expression in colorectal cancer progression and metastasis.

Galectin-3 is a beta-galactoside-specific lectin that binds to laminin sugar-sites and is involved in tumor malignancy. Galectin-3 expression in relation to primary tumor and liver metastasis of colorectal cancer was examined to determined its involvement in cancer progression and metastasis. Immunohistochemical staining of galectin-3 was performed on 117 primary lesions and 15 liver metastases of colorectal cancer using TIB166 monoclonal antibody. The expression of galectin-3 was evaluated by grading the intensity of the staining as either negative, weakly positive, or strongly positive. Normal mucosa of all patients were strongly positive for galectin-3, but the staining in these tissues was still significantly less than in the primary lesions of the cancer (31.6%). Galectin-3 expression in the primary lesions was significantly increased, correlating with the progression of clinical stage (p=0. 0224), liver metastasis (p<0.0001), venous invasion (p=0.0048), and lymph node metastasis (p=0.0289). Liver metastatic lesions also showed up-regulated levels of galectin-3 compared to the primary lesions (p=0.0030). The group showing strongly positive galectin-3 had a significantly poorer prognosis than the negative/weakly positive group in terms of disease-free survival (p=0.0224). The strong expression of galectin-3 in colorectal cancer correlates with cancer progression, liver metastasis, and poor prognosis for patients.

Adenocarcinoma↗

[A consideration for indexes of global improvement rating by physicians in bronchial asthma].

As the minimum items required for GIR evaluation, morning Peak Respiratory Flow Rate (PEFR), evening PEFR, asthma scores and symptom scores were selected based on Cronbach's alpha, an index of internal consistency. Optimum categorization of total improvement scores (TS), or principal component scores (PCS) was conducted based on agreement with the physician's evaluation of GIR. Good agreement was observed between optimally categorized moderate and marked improvement rate in TS or PCS and moderate and marked improvement rate in the physician's evaluation of GIR. The rate of agreement between optimally categorized TS or PCS and distribution of GIR was about 93% if allowance is made for discrepancy of one stage. Our assessment that TS which is objective and practical was useful as criteria for evaluating GIR.

Asthma↗

Zinc stimulates DNA synthesis during its antiapoptotic action independently with increments of an antiapoptotic protein, Bcl-2, in porcine kidney LLC-PK(1) cells.

Cadmium, an environmental pollutant, caused nephroptosis that was inhibitable by zinc. The mechanism of the antiapoptotic action of zinc is poorly understood. In this study, we found the stimulation of DNA synthesis, as assessed by bromodeoxyuridine incorporation, during prevention by zinc of apoptosis, suggesting that the proliferactive nature of zinc contributes to its inhibition of apoptosis. This finding was consistent with the result that the cells driven by dialyzed fetal bovine serum were resistant to apoptotic stimuli of cadmium. Furthermore, zinc activated the expression of endogenous Bcl-2 proteins. However, overexpression of Bcl-2 proteins by transfection did not facilitate zinc-mediated DNA synthesis. Thus, one possible role of zinc in the prevention of apoptosis is to promote DNA synthesis independently with activation of antiapoptotic proteins Bcl-2.

Animals↗

[Peak flow values in assessment of global improvement rating in bronchial asthma].

The results suggest a marked correlation between Global Improvement Rating (GIR) and change from baseline in PEFRs and that increase from baseline in PEFR was practicable as an evaluation index. Best categorization was determined based on weighted agreement (kappa *) between the increase from baseline in morning and evening PEFRs or mean PEFR (in l/min). For categorization of increase from baseline, maximum agreement with the physician's global improvement rating (GIR) was achieved by categorizing the increase in PEFR into 5 categories using Akaike's Information Criterion (AIC). Categorization into the 5 grades of > or = 50, 50-> or = 35, 35-> or = 10, 10-> or = -5 and < -5 for morning PEFR & mean PEFR and > or = 45, 45-> or = 10, 10-> or = -10, -10-> or = -45 and < -45 for increase in evening PEFR was optimal. Improvement scores (a tentative name) were prepared by maximization of agreement rate between total of scores and GIR.

Adult↗

[Study of chronic graft-vs-host disease, infection and immune reconstitution in patients surviving more than one year after bone marrow transplantation from unrelated donors].

We studied the immune reconstitution and incidence of chronic graft-vs-host disease (GVHD) and infection in 25 patients who survived more than 1 year after bone marrow transplantation (BMT) from unrelated donors for treatment of leukemia. Of the 25 patients, 4 died after 1 year post-transplantation. The causes of death were relapse of leukemia (2 patients), obstructive bronchiolitis (1 patient), and hepatic failure (1 patient). Only 2 of 14 patients who were under 30 years of age at the time of their BMT developed chronic GVHD, however, 7 of 11 patients 30 years of age or older developed chronic GVHD. Lower karnofsky scores were displayed by 6 of the older patients with chronic GVHD but by none of the younger patients with chronic GVHD. These results underscored the importance of care for older patients with chronic GVHD.CD4-positive T cells, and especially CD4 * CD45RA-positive T cells, had not recovered to a normal range even 2 years after BMT. Longer follow-up will be necessary.

Adolescent↗

Laparoscopic distal pancreatectomy with preservation of the spleen.

We describe a case of chronic pancreatitis treated by laparoscopic distal pancreatectomy with conservation of the spleen involving the resection of the splenic vessels. A proximal ligation of the splenic artery and vein was performed, followed by transection of the body of the pancreas. Retroperitoneum was dissected to the left by mobilizing the stump of the transected pancreas. The entire distal pancreas was freed posteriorly. The distal splenic artery and vein were ligated and divided individually adjacent to the tail of the pancreas at the hilum of the spleen. The points of this operation were to ligate the splenic artery and vein at both sides of the resected pancreas and to save the spleen with the blood supply continuing through the short gastric vessels and the splenocolic ligament. This operation with splenic preservation is more suitable for a patient who is a candidate for laparoscopic distal pancreatectomy, which will minimize the operation time, preserve the useful immunologic role of the spleen, and obtain the intact resected specimen. Furthermore, this procedure is useful in chronic pancreatitis patients because it avoids the difficult dissection of the posterior pancreas off of the splenic vessels.

Aged↗

[Present situation and future subjects of N.SAS study--based on experience of managing data center].

The "National Surgical Adjuvant Study" (N-SAS) was established as a study group on carcinostatics on the market as part of the Ministry of Health and Welfare's 1995/1996 consignment project. Patient registration started in October 1996, and later it was restructured as a consignment study by Taiho Pharmaceutical Co., Ltd. in April 1997. It still continues to date. EPS Co., Ltd. has operated the "N.SAS Data Center" to conduct three clinical trials of N.SAS study. In the following, we analyse the current situation and subjects of N.SAS study from the viewpoint of the data center, recognising the necessity of infrastructure at medical institutions while complying with enforcement of newly GCP and GPMSP. First, the organization and function of N.SAS, and the role and position of data center on N.SAS study, are explained. Some notes are introduced from conducting In-house Monitoring on N.SAS, especially methods and formation of communicating information between N.SAS Data Center and institutions. We also propose an infrastructure which will be essential for smooth promotion of long-term and large-scale trials like the N.SAS study.

Clinical Trials as Topic↗

Association of extracellular-superoxide dismutase phenotype with the endothelial constitutive nitric oxide synthase polymorphism.

The distribution of extracellular-superoxide dismutase (EC-SOD) levels in healthy Australian subjects was consistent with two distinct phenotypes in which the smaller group of subjects (3.3%) had 15-fold higher levels. The EC-SOD levels in individuals homozygous for endothelial constitutive nitric oxide synthase 4a (ecNOS4a), a rare allele for ecNOS repeat polymorphism at intron 4, were significantly lower than those in ecNOS4A/a and ecNOS4AIA subjects. Furthermore, NO levels were negatively correlated with the EC-SOD levels in common EC-SOD phenotype subjects. Whilst the mechanism remains speculative, it is possible that there is a significant interaction between EC-SOD and ecNOS, or that common factor(s), either genetic or environmental, influence both of them.

Adolescent↗