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Biomedical subjects

T Aoki

Publications and source records attributed to T Aoki.

At least 127 records · Page 7Linked to original sources
PubMed2001

[Mechanisms of morphine-induced rewarding effect: involvement of NMDA receptor subunits].

The glutamate receptor contributes to excitatory synaptic transmission in the central nervous system and plays an important role in memory acquisition, learning and neurological disorders. Molecular cloning studies have revealed that NMDA receptors consist of two families, the NR1 and NR2A-NR2D subunits, and NMDA receptors are thought to be pentameric or tetrameric complexes of the NR1 subunit with one or more of the NR2 subunits. It has been proposed that NMDA receptors are implicated in the development of opioid dependence. The non-selective NMDA receptor antagonist dizocilpine has been shown to suppress not only physical but also psychological dependence produced by morphine. An intracerebroventricular (i.c.v.) treatment with a specific antibody against the carboxyl-terminal region of the NR2B subunit abolishes the morphine-induced place preference, whereas antibodies against the NR1 and NR2A subunits do not affect the rewarding effect of morphine, indicating that the blockade of the NR2B subunit suppresses the development of the morphine-induced rewarding effect. Under these conditions, the NR2B subunit protein is up-regulated in the limbic forebrain of morphine-conditioned mice. These findings suggest that the NMDA receptor, especially NR2B subunit, is an important modulator of the development and/or expression of psychological dependence on morphine.

Animals↗
PubMed2001

Muscle sympathetic nerve activity in patients with lumbar spinal canal stenosis.

The present study aimed to measure sensory nerve conduction velocity (SNCV) and muscle sympathetic nerve activity (MSA) in both normal subjects and patients with lumbar spinal canal stenosis (LSCS), and to determine what sensory and sympathetic nerve systems relate to the development of abnormal sensation in the lower limbs of the patients. The study population was 12 patients and 10 age-matched healthy control subjects. A statistical difference in the mean MSA intervals was found between the LSCS patients and the normal subjects. There was a fairly large difference between them in the values of the standard deviations as one of the parameters to determine the degree of fluctuation of MSA. These results suggest the LSCS patients have shorter MSA intervals and narrower fluctuations of MSA than normal subjects. As for the range of fluctuation of the MSA intervals and SNCV, the faster the SNCV, the wider the range of fluctuation of MSA intervals in the normal subjects. Many patients with LSCS seem to maintain a correlation between SNCV and MSA intervals. This suggests that even in cases of LSCS, human homeostasis works to keep the relationship between sympathetic nerve function and somato sensory nerve function to some extent. A few LSCS patients showed no correlation between MSA and SNCV. These patients were rather old, suffered spinal stenosis in the relatively higher levels of the spinal canal, and had suffered from the disease for longer than the mean period of all the patients. When the peripheral nerves or cauda epuina are chronically compressed, the nerve systems can not maintain the relationship between them, which finally results in failure. It is suggested that the disrupted coordination between sympathetic nerve function and somato sensory nerve function is one of the reasons why abnormal sensations occur in the lower extremities of LSCS patients.

Aged↗
PubMed2001

Tissue inhibitor of metalloproteinases 1 and 2 directly stimulate the bone-resorbing activity of isolated mature osteoclasts.

Tissue inhibitor metalloproteinases 1 (TIMP-1) and 2 have been reported to inhibit bone resorption. However, here, we report the direct action of both TIMP-1 and TIMP-2 on isolated rabbit mature osteoclasts to stimulate their bone-resorbing activity at significantly lower concentrations (approximately ng/ml) than those (approximately microg/ml) required for the inhibition of bone resorption. The cell population used in this study consisted of a mature osteoclast population with >95% purity. TIMP-1 (approximately 50 ng/ml) and TIMP-2 (approximately 8-10 ng/ml) increased the pit area excavated by the isolated mature osteoclasts. The stimulatory effects of TIMPs were abolished by simultaneous addition of anti-TIMP antibodies. At higher concentrations, the stimulation of bone resorption decreased reversely to the control level. The magnitude of the stimulatory effect of TIMP-2 was more than that of TIMP-1. Metalloproteinase inhibitors such as BE16627B and R94138 could not replace TIMPs with respect to the bone-resorbing activity, suggesting that the osteoclast-stimulating activity of TIMPs was independent of the inhibitory activity on matrix metalloproteinases (MMPs). TIMPs stimulated tyrosine phosphorylation of cellular proteins in the isolated mature osteoclasts. Both herbimycin A, an inhibitor of tyrosine kinases, and PD98059 and U0126, inhibitors of mitogen-activated protein kinase (MAPK), completely blocked the TIMP-induced stimulation of osteoclastic bone-resorbing activity. On the plasma membrane of osteoclasts, some TIMP-2-binding proteins were detected by a cross-linking experiment. These findings show that TIMPs directly stimulate the bone-resorbing activity of isolated mature osteoclasts at their physiological concentrations and that the stimulatory action of TIMPs is likely to be independent of their activities as inhibitors of MMPs.

Acetamides↗
PubMed2001

Neurogenic pulmonary edema and large negative T waves associated with subarachnoid hemorrhage.

We describe a 72-year-old woman with hypertension who developed acute neurogenic pulmonary edema and giant negative T waves on electrocardiography (ECG) due to subarachnoid hemorrhage. The patient was alert and complained of precordial chest discomfort, dyspnea and shoulder stiffness. Echocardiography demonstrated normal left ventricle contraction with hypertrophy. Computed tomography (CT) and subsequent cerebral angiography revealed subarachnoid hemorrhage and saccular aneurysm at the anterior communicating artery. It is important to consider the possibility of subarachnoid hemorrhage when a patient shows pulmonary edema and ECG abnormalities even without typical clinical signs of subarachnoid hemorrhage.

Aged↗
PubMed2001

Acute pericarditis associated with 5-aminosalicylic acid (5-ASA) treatment for severe active ulcerative colitis.

A 17-year-old male who had been diagnosed with ulcerative colitis was prescribed 80 mg prednisolone and 1,500 mg 5-aminosalicylic acid (5-ASA) per day. Two weeks after initiating therapy, he was referred to our hospital for evaluation of chest pain and high fever. Electrocardiography (ECG) showed ST elevation in limb and precordial leads. Chest pain with high fever and ECG changes were resolved after 5-ASA was discontinued. Three weeks later, the administration of a low dose of 5-ASA was associated with the immediate recurrence of pericarditis associated with chest pain, suggesting a hypersensitive reaction to 5-ASA in this patient.

Adolescent↗
PubMed2001

A study of Xlim1 function in the Spemann-Mangold organizer.

The Spemann-Mangold organizer is required in amphibian embryos to coordinate cell fate specification, differentiation of dorsal cell types and morphogenetic movements at early stages of development. A great number of genes are specifically expressed within the organizer, most of them encoding secreted proteins and transcription factors. The challenge is now to uncover genetic cascades and networks of interactions between these genes, in order to understand how the organizer functions. The task is immense and requires loss-of-function approaches to test the requirement for a given factor in a specific process. For transcription factors, it is possible to generate inhibitory molecules by fusing the DNA binding region to a repressor or activator domain, which should in principle antagonize the activity of the endogenous protein at the level of the DNA targets. We used this strategy to design activated and inhibitory forms of the LIM homeodomain transcription factor Lim1, which is encoded by an organizer gene involved in head development, as revealed by analyses of knockout mice. We found that Lim1 is a transcriptional activator, and can trigger dorso-anterior development upon ventral expression of hyperactive forms, in which Ldb1 is fused to Lim1. Using inhibitory Lim1 fusion proteins, we found that Lim1, or genes closely related to it, is required for head formation as well as for notochord development. Co-expression experiments revealed that Lim1 is required downstream of the early organizer factor Siamois, first, to establish the genetic program of the organizer and second, to mediate the action of organizer agents that are responsible for blocking ventralizing activities in the gastrula.

Animals↗
PubMed2001

[Antimicrobial susceptibility of Pseudomonas aeruginosa isolated in Fukushima Prefecture].

We investigated the susceptibility of Pseudomonas aeruginosa (isolated from the sputum of patients with respiratory infection in 4 medical institutions in Fukushima Prefecture) to 8 beta-lactam antibiotics including three carbapenems and relationships among MICs of antibiotics tested. The MIC90 values for a total of 216 strains were 6.25 micrograms/ml for meropenem, 12.5 micrograms/ml for imipenem and ceftazidime, 25 micrograms/ml for panipenem and cefsulodin, 50 micrograms/ml for cefpirome and over than 200 micrograms/ml for cefoperazone and piperacillin. The frequency of resistance of these strains to each antibiotic was as follows: The resistant strains were 19 (8.8%) for meropenem, 34 (15.7%) for imipenem and ceftazidime, 50 (23.1%) for cefsulodin, 72 (33.3%) for panipenem, 76 (35.2%) for piperacillin and 90 (41.7%) for cefpirome. Eighteen strains (18.3%) of 19 meropenem resitant straisn were resistant to imipenem and panipenem, but 16 strains of the 34 imipenem-resistant strains and 54 strains of the 72 panipenem-resistant strains were susceptible to meropenem. In investigation of isolation of multi-resistant Pseudomonas aeruginosa, the susceptibility of strains tested to 7 antibiotics except cefoperazone was as follows: The strains susceptible to all the 7 antibiotics were 92 strains (42.6%), and 33 strains (15.2%) were resistant to 2 antibiotics, 31 strains (14.4%) were resistant to 1 antibiotic, 21 strains (9.7%) were resistant to 3 antibiotics, 13 strains (6.0%) were resistant to 5 antibiotics, 9 (4.2%) were resistant to 4 and 7 antibiotics, and 8 strains (3.7%) were reistant to 6 antibiotics. Since the emergence of these multi-resistant strains is closely related to frequent use of antibiotics for nosocomial infections, special attention should be paid to the antimicrobial susceptibility of Pseudomonas aeruginosa and the situation of antibiotic resistant strains.

Anti-Bacterial Agents↗
PubMed2001

[The involvement of phosphoinositide 3-kinase (PI3-Kinase) and phospholipase C gamma (PLC gamma) pathway in the morphine-induced supraspinal antinociception in the mouse].

The present study was designed to investigate whether the phospholipase C gamma (PLC gamma)/phosphoinositide 3-kinase (PI3-Kinase) pathway could participate in the expression of the supraspinal antinociception induced by intracerebroventricular (i.c.v.) administration of mu-opioid receptor agonist in the mouse. The i.c.v. pretreatment with PI3-Kinase inhibitors, wortmannin and LY294002, and a specific antibody to PLC gamma 1 significantly attenuated the antinociception produced by either i.c.v. or systemic (s.c.) injection of a prototype of mu-agonist morphine. The s.c. injection of morphine produced a marked increase in the level of membrane-bound PLC gamma 1 isoform as compared to that from the saline-treated mice. This up-regulation of PLC gamma 1 by morphine was significantly inhibited by i.c.v. pretreatment with LY294002, indicating that morphine can activate PLC gamma 1 through the stimulation of PI3-Kinase. Pretreatment with a specific IP3 receptor inhibitor xestospongin C suppressed the morphine-induced antinociception in a dose-dependent manner. Recent studies have demonstrated that PI3-Kinase can be activated by G beta gamma, but not by G alpha subunit. In the present study, i.c.v. pretreatment with specific antibodies to G12 alpha and G beta gamma significantly suppressed the antinociception induced by morphine, whereas the specific antibody to Gq/11 alpha did not affect the antinociception induced by morphine. The present findings suggest that the supraspinal antinociception induced by mu-opioid receptor agonist may be mediated, at least in part, by the activation of PLC gamma through the stimulation of PI3-Kinase modulated by G beta gamma subunit.

Analgesics, Opioid↗
PubMed2001

[Usefulness of chemotherapy with CPT-11 in clinic for three colorectal cancer in terminal stage].

In our clinic we performed chemotherapy with CPT-11 in three cases of non-resectable advanced colorectal cancer, including two cases of multiple liver metastasis and one case of multiple lung metastasis, and obtained various alleviating effects. Heretofore two factors. 1. direct effect and 2. longevity effects, have been focused on when evaluating the effect of various chemotherapy regimens. However, the symptoms of these patients were alleviated by the chemotherapy without obtaining either of the two effects. Furthermore, their performance statuses were improved. It is therefore sufficiently beneficial for patients in the terminal stage to undergo the chemotherapy. The patient in the terminal stage should be taken care of in the clinic rather than in the hospital. At present, safe and effective therapies on an ambulant basis have not been established. It will now be necessary for us to evaluate the many accumulated cases. It is conceivable that chemotherapy with CPT-11 in the clinic would be extremely useful for patients in the terminal stage for the purpose of improving the QOL, if the dose and administration interval of CPT-11 are given sufficient attention.

Ambulatory Care↗
PubMed2001

[A case of AFP producing early gastric cancer successfully treated with small dose CDDP and 5-FU (PF) therapy].

A case of AFP producing early gastric cancer successfully treated with a small dose of CDDP and 5-FU therapy administered intermittedly is reported with a review of the literature. A 63-year-old male was admitted to our hospital because of liver metastasis with a high level of serum AFP (185.8 ng/ml) three months after gastrectomy. Systemic chemotherapy was performed twice with a regimen of CDDP 20 mg and 5-FU 750 mg/day in 5 days. After hepatic arterial infusion chemotherapy (HAIC) was performed once, the patient obtained partial response according to CT scan and was discharged. After he underwent HAIC once as an outpatient, liver metastasis completely disappeared 5 months after surgery. He was administered oral 5-FU, 150 mg and Krestin 3.0 g/day and underwent HAIC with CDDP 20 mg and 5-FU 750 mg/day every 2 weeks. After serum AFP level was returned to the normal range 7 months after surgery; HAIC was performed every 4 weeks and continued until one year after surgery. One year and 11 months after surgery, serum AFP remains within the normal limit and there is no evidence of recurrence.

Adenocarcinoma↗