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Biomedical subjects

M Takasaki

Publications and source records attributed to M Takasaki.

At least 19 recordsLinked to original sources

Asymptomatic myocardial ischemia in relation to carotid artery stenosis among patients with aortic aneurysm.

AIM: The prevalence of asymptomatic coronary artery stenosis in relation to carotid artery stenosis is influenced by the underlying disease and has yet to be clarified. METHODS: A total of 124 consecutive Japanese patients with aortic aneurysm, but without symptoms of coronary artery stenosis, were divided into 2 groups on the basis of carotid ultrasonography: the carotid stenosis group (>or=50% luminal diameter narrowing) and the non-stenosis group. Myocardial imaging was performed using thalium-201 chloride and adenosine triphosphate disodium. RESULTS: The mean age and incidence of both cerebrovascular disease and peripheral artery disease were significantly higher in the stenosis group (n=24) than the non-stenosis group (n=100). Defining both fixed and reversible hypoperfusion as positive on the basis of myocardial imaging, a significantly higher number of positive findings were found in the stenosis group (15/24; 62.5%) than in the non-stenosis group (32/100, 32.0%), (Odds ratio: 3.54; p<0.01). The distributions of hypoperfusion defects in the stenosis group were similar to those in the non-stenosis group, but fixed hypoperfusion was more frequently seen in the stenosis group. CONCLUSION: The high prevalence of positive findings in the stenosis group indicates that carotid artery stenosis is frequently associated with coronary artery stenosis even in asymptomatic patients, and could be an indicator for advanced atherosclerosis of the coronary artery. The results confirm that stress myocardial imaging is invaluable in the detection of coronary artery stenosis, particularly in patients with carotid arteriosclerosis.

Aged↗

Antitumor activity of a phenoxazine compound, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one against human B cell and T cell lymphoblastoid cell lines: induction of mixed types of cell death, apoptosis, and necrosis.

PURPOSE: We studied the antitumor activity of 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx), which was synthesized by the reactions of 2-amino-5-methylphenol with bovine hemoglobin, on human B cell lymphoblastoid cell lines, P3HR-1 and Raji derived from African Burkitt's lymphoma, and the human T cell lymphoblastoid cell line Molt-4. We also studied whether Phx might cause apoptosis and necrosis in these cells. METHODS: We evaluated cell viability and apoptosis and necrosis of the cells in the presence of Phx, by using agarose gel electrophoresis, flow cytometry, and fluorescence microscopy. RESULTS: Phx suppressed the viability of P3HR-1, Raji, and Molt-4 cells, though the suppression patterns were different, i.e., Phx suppressed the viability of P3HR-1, Raji, and Molt-4 cells at higher concentrations, while the drug enhanced the viability of Raji cells, but not those of P3HR-1 and Molt-4 cells at lower concentrations. To investigate which type of cell death - apoptosis or necrosis - is induced by Phx, induction of DNA ladder, phosphatidylserine externalization, and propidium iodide-permeable cells were examined in Phx-treated cells. Although Phx did not induce DNA ladder formation, it induced the phosphatidylserine externalization and propidium iodide-permeable cells, suggesting that Phx caused a mixed type of cell death, both apoptosis and necrosis. The population of early stage apoptotic cells was dominant in Raji cells, and that of the late stage apoptotic/necrotic cells was dominant in Molt-4 cells after 72-h treatment with Phx. The population of the early stage apoptotic cells and the late stage apoptotic/necrotic cells was almost equal in P3HR-1 cells in the presence of Phx, though the population of both types of cells increased with time. The nuclear morphological analysis of Phx-treated Raji, P3HR-1, and Molt-4 cells also showed that Phx induces apoptosis. CONCLUSIONS: The present results suggest that Phx shows antitumor activity against human B cell-derived and T cell-derived lymphoblastoid cell lines, in vitro, causing apoptosis and necrosis.

Annexin A5↗

Cancer chemopreventive activity of phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, from Polygonum lapathifolium.

To search for cancer chemopreventive agents from natural resources, many phytochemicals have been screened using the in vitro synergistic assay indicated by the inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA). Two phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, were isolated from the aerial part of Polygonum lapathifolium as inhibitors on the EBV-EA induction. These compounds also exhibited significant anti-tumor-promoting effects on mouse two-stage skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA, as an initiator) and TPA as a promoter. Further, vanicoside B exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors initiated with an NO donor, NOR-1.

Animals↗

MK-801 reduces non-noxious stimulus-evoked Fos-like immunoreactivity in the spinal cord of rats with chronic constriction nerve injury.

We investigated the role of N-methyl-D-aspartate (NMDA) receptors on non-noxious stimulus-induced pain by examining the effect of MK-801, a non-competitive NMDA receptor antagonist, on Fos-like immunoreactivity (FLI) in the spinal dorsal horn by non-noxious stimulation to rats with chronic constriction injury (CCI) of the sciatic nerve. In CCI rats that did not receive the non-noxious stimulus, FLI was significantly increased in laminae V/VI of the dorsal horn at the 7th and 14th days after surgery relative to sham rats. When CCI rats received non-noxious stimuli, rubbing the plantar of the hind paw, FLI in laminae I/II at the 14th day was significantly increased relative to CCI rats that did not receive the stimulation. In sham rats, the same stimulus significantly decreased FLI in laminae III/IV and V/VI at the 7th and 14th day. When MK-801 was administered intraperitoneally prior to non-noxious stimulation in CCI rats at the 14th day after surgery, the stimulus-induced FLI in laminae I/II in CCI rats was significantly reduced. This study indicates that NMDA receptor is involved in upregulating FLI in response to non-noxious stimulation of CCI rats.

Animals↗

Magnetization transfer measurements of the hippocampus in the early diagnosis of Alzheimer's disease.

We measured magnetization transfer ratios (MTRs) of the hippocampus in 38 patients with Alzheimer's disease (AD), including very mild (Clinical Dementia Rating [CDR] 0.5, n=12), mild (CDR 1, n=14), and moderate stages (CDR 2, n=12), and in 21 healthy elderly control subjects. Medial temporal lobe atrophy was graded subjectively on a five-point scale by two observers blinded to clinical data. Compared with the controls, each of the AD groups, including the very mild group, had significant atrophy of the medial temporal lobe and a decrease in MTRs of the hippocampus. Logistic regression analysis revealed that the overall discrimination rate with MTR measurement and visual analysis of the atrophy was 85% and 73% between the control group and the CDR 0.5 group, 89% and 80% between the control group and the CDR 1 group, and 100% and 91% between the control group and the CDR 2 group, respectively. MTR measurements may provide additional information in detecting structural damage of the hippocampus of AD and be helpful in providing improved diagnosis and early detection of AD.

Aged↗

Structural characteristics of the N-glycans of two isoforms of prostate-specific antigens purified from human seminal fluid.

Prostate-specific antigen (PSA) is a glycosylated chymotrypsin-like serine protease and is found mainly in prostatic tissue and seminal fluid. We purified two forms of PSA (PSA-A and PSA-B) from human seminal fluid with pI values of approx. 7.2 and approx. 6.9, respectively. To characterize the N-glycans of the two isoforms, the sugar chains were liberated by hydrazinolysis followed by N-acetylation, and derivatized with 2-aminobenzamide. Both PSA-A and PSA-B contained mono- and disialylated sugar chains, although PSA-B had a much higher content of the latter. After removal of sialic acid residues by sialidase digestion, mono- and biantennary N-glycans and three outer chain moieties (Galbeta1-4GlcNAcbeta1-, GlcNAcbeta1-, GalNAcbeta1-4GlcNAcbeta1-) were found in both samples. However, the ratios of each N-glycan were different. These results indicate that PSA-A and PSA-B differ not only in their sialic acid contents, but also in their outer chain features.

Carbohydrate Sequence↗

Nociceptin/orphanin FQ and [Phe(1)psi(CH2-NH)Gly2]nociceptin(1-13)NH2 modulates the activity of hypothalamic paraventricular nucleus neurons in vitro.

Nociceptin, also known as orphanin FQ (N/OFQ), an endogenous ligand for the orphan opioid receptor-like(1) (ORL(1)) receptor, is moderately expressed in the hypothalamic paraventricular nucleus (PVN) involved in the integrative control of the function of the endocrine and autonomic nervous systems. Our previous study demonstrated that intracerebroventricular administration of N/OFQ elicits an inhibitory action on the function of the cardiovascular and sympathetic nervous systems in conscious rats. However, the effects of N/OFQ on PVN neurons have not been examined. We investigated the effects of N/OFQ on PVN neurons using a whole-cell patch-clamp recording technique in rat brain slices. N/OFQ (30-1000 nM) hyperpolarized membrane potentials in type 1 and type 2 neurons of the PVN classified by the electrophysiological property. [Phe(1)psi(CH2-NH)Gly2]nociceptin(1-13)NH2 (Phepsi) (1-9 microM), a presumed competitive antagonist of the ORL(1) receptor, also hyperpolarized membrane potential in both types of neurons. In voltage clamp studies, N/OFQ (3-3000 nM) activated a K+ current concentration-dependently in 69.7% of PVN neurons with an EC(50) of 72.4+/-12 nM. Phepsi (100-9000 nM) also activated a K+ current with an EC(50) of 818+/-162 nM in PVN neurons, and significantly reduced the amplitude of the N/OFQ-stimulated current. The N/OFQ-induced current was not antagonized by the classical opioid receptor antagonist naloxone and putative antagonist nocistatin. These findings suggest that N/OFQ may have a functional role in the PVN.

Animals↗

Intrathecal pre-administration of fentanyl effectively suppresses formalin evoked c-Fos expression in spinal cord of rat.

PURPOSE: To investigate whether the timing of intrathecal administration of the opioid analgesic fentanyl, alters noxious stimulus-evoked neuronal activity in the rat spinal cord. METHODS: A 5% formalin solution was used as the noxious stimulant. For the pretreatment group, a dose of 0.001 to 0.5 microg of fentanyl was injected intrathecally ten minutes prior to formalin injection. Early and late post-treatment groups received 0.01 to 0.5 microg fentanyl, five and 60 min after formalin injection respectively. The effect of fentanyl was confirmed with naloxone. The level of c-Fos expression was determined in each treatment group to indicate neuronal activity. RESULTS: Pretreatment and early post-treatment groups showed suppression of c-Fos activity compared to the vehicle (P <0.01). The late post-treatment group showed no difference in c-Fos activity compared to the vehicle (P=NS). Pretreatment with fentanyl showed the most profound suppression of c-Fos expression (P <0.01). In addition, pretreatment injection showed a greater suppression of c-Fos activity in the deep (14.6% of control) compared to the superficial laminae (32.7% of control; P <0.01), whereas the early post-treatment group showed a universal decrease in c-Fos activity (49.2% of control in laminae I and II, 50.4% of control in laminae III and IV and 51.8% of control in laminae V and VI). Naloxone reversed the action of fentanyl on c-Fos activity. CONCLUSION: Inasmuch as: 1) c-Fos expression can be equated with behavioural changes; 2) injection of formalin is an appropriate model of surgical trauma; and 3) animal data can be transports to humans, these results suggest that fentanyl would be an effective pre-emptive analgesic.

Analgesia↗

Magnetisation transfer measurements of the subcortical grey and white matter in Parkinson's disease with and without dementia and in progressive supranuclear palsy.

We measured the magnetisation transfer ratio (MTR) in the subcortical grey and white matter of 11 patients with idiopathic Parkinson's disease (PD) without dementia, six with PD with dementia (PDD), six with progressive supranuclear palsy (PSP), and 12 elderly control subjects to assess regional differences in structural brain damage. There were no significant differences in MTR in any region between PD and controls. However, patients with PDD had significantly lower MTR in the subcortical white matter, including the frontal white matter and the genu of the corpus callosum than the controls, whereas PSP had significantly lower MTR in the subcortical grey matter, including the putamen, globus pallidus and thalamus, in addition to the subcortical white matter. This suggests that regional patterns of structural brain damage can be detected using the magnetisation transfer technique. Measurement of MTR in the subcortical grey and white matter may be useful in differential diagnosis.

Aged↗

Local infusion of nerve growth factor attenuates myelinated nerve fiber sprouting into lamina II of the spinal dorsal horn and reduces the increased responsiveness to mechanical stimuli in rats with chronic constriction nerve injury.

PURPOSE: To clarify the relationship between allodynia and the sprouting of myelinated fibers, we examined whether the administration of nerve growth factor (NGF) affected the paw withdrawal response to non-noxious mechanical stimuli and the sprouting of myelinated fibers into lamina II of the spinal dorsal horn, using a chronic constriction injury model of the sciatic nerve. METHODS: Mechanical allodynia was determined as the threshold of the withdrawal response stimulated by von Frey filaments. Sprouting was examined using horseradish peroxidase conjugated to the B fragment of cholera toxin (B-HRP). NGF was continuously infused into the site of nerve injury for 14 days after nerve ligation. RESULTS: With vehicle infusion, significantly increased responsiveness to mechanical stimuli was observed on postoperative days (PODs) 5, 7, and 14 after ligation, compared with before surgery, and B-HRP-positive fibers were newly localized in lamina II on PODs 7 and 14. Infusion of NGF reduced the responsiveness to mechanical stimuli on 5, 7, and 14 PODs and B-HRP-positive fibers in lamina II on PODs 7 and 14. CONCLUSION: We propose that the suppression of the increased responsiveness to mechanical stimuli produced by NGF could be related to the disappearance of B-HRP-positive fibers in lamina II.

Journal Article↗

New phenylpropanoid esters of sucrose from Polygonum lapathifolium.

Four new phenylpropanoid esters of sucrose, lapathosides A (1), B (2), C (3), and D (4), were isolated from the aerial parts of Polygonum lapathifolium together with known esters, vanicoside B (5) and hydropiperoside (6). The structures of 1-4 were determined by spectral (1D and 2D NMR and MS) analysis. Lapathoside A (1) and vanicoside B (2) showed significant inhibitory effects on the Epstein-Barr virus early antigen activation by tumor-promoters.

Animals↗

A new method to analyze basic rest-activity cycle.

A new method was proposed to analyze a basic rest-activity cycle (BRAC), termed BRAC-A. This method calculates a significant cycle length by chi-squared method and the starting points of a resting phase and an active one by analysis of the array consisting of the segmented time series in the same length. Using 20 3-day computer-simulated time series of standard deviation in fetal heart rate fluctuation with known periodicity of the BRAC, we demonstrated that the BRAC-A was a useful tool to reveal the characteristics of the BRAC.

Activity Cycles↗

Changes in fractal structure of heart rate variability during a nap in one case.

The objective of the present study was to analyze fractal structures of adult heart rate (HR) variability during a nap. Fractal analysis was carried out in one case over consecutive 10-min time series of HR, which were simultaneously recorded with electroencephalogram. Scaling relationships showed cross-over patterns characterized by alphas and alphal (i.e. slopes above and below a cross-over point). The alphas and alphal were black and white noise at Stage 4 of NREM sleep, and black and 1/f noise in REM sleep. Cross-over points changed from the first to second sleep cycle. We demonstrate the multifractal structures of HR variability during a nap in the present case.

Adult↗

The characterization of bronchoalveolar lavage fluid in very elderly patients with cerebrovascular disease.

BACKGROUND: Elderly patients with cerebrovascular disease have a high frequency of pneumonia due to impaired immune function and the occurrence of micro-aspiration. METHODS: We performed bronchoalveolar lavage in 11 very elderly subjects with cerebrovascular disease and 9 healthy volunteers to investigate whether there were changes of local immunity in the lungs of the elderly subjects. The total cell count, the cell characteristics, and the lymphocyte subsets in bronchoalveolar lavage fluid were compared between the two groups. RESULTS: A significant increase in the total cell count as well as in the number of neutrophils and CD8(+) T cells was observed in the elderly group. In addition, the mean CD4/CD8 lymphocyte ratio was lower in the elderly patients than in the healthy volunteers. CONCLUSIONS: These observations suggest that silent micro-aspiration occurs in many elderly individuals with cerebrovascular disease and that pulmonary defenses decrease with age.

Adult↗

Orexin depolarizes rat hypothalamic paraventricular nucleus neurons.

Orexins, also called hypocretins, are newly discovered hypothalamic peptides that are thought to be involved in various physiological functions. In spite of the fact that orexin receptors, especially orexin receptor 2, are abundant in the hypothalamic paraventricular nucleus (PVN), the effects of orexins on PVN neurons remain unknown. Using a whole cell patch-clamp recording technique, we investigated the effects of orexin-B on PVN neurons of rat brain slices. Bath application of orexin-B (0.01-1.0 microM) depolarized 80.8% of type 1 (n = 26) and 79.2% of type 2 neurons tested (n = 24) in the PVN in a concentration-dependent manner. The effects of orexin-B persisted in the presence of TTX (1 microM), indicating that these depolarizing effects were generated postsynaptically. Addition of Cd(2+) (1 mM) to artificial cerebrospinal fluid containing TTX (1 microM) significantly reduced the depolarizing effect in type 2 neurons. These results suggest that orexin-B has excitatory effects on the PVN neurons mediated via a depolarization of the membrane potential.

Animals↗

Anti-tumor-promoting activity of the diterpene from Excoecaria agallocha. II.

Eight new diterpenoids (1-8) have been isolated from the wood of Excoecaria agallocha (Euphorbiaceae) and their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) in Raji cells were examined to search for potent anti-tumor-promoters from natural resources. Of these compounds, the secolabdane-type diterpenoid, compound 7 exhibited a remarkable inhibitory effect on EBV-EA induction, and a significant anti-tumor-promoting effect in the mouse two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanovl-phorbol-13-acetate.

Animals↗

Effect of dietary short-chain fructooligosaccharides on the cecal microflora in gastrectomized rats.

Total gastric resection is known to lead to changes in the microflora in the whole gastrointestinal tract. Dietary short-chain fructooligosaccharides (Sc-FOS) have been shown to also induce a change in the microflora in the large bowel by promoting an increase in the numbers of Bifidobacterium and Lactobacillus which have beneficial effects on the host. In the present study, 4-week-old male Sprague-Dawley rats received total gastrectomy or laparotomy, and each of these surgically treated groups was randomly divided into two experimental diet groups and given a 7.5% Sc-FOS diet or control diet. Enumeration and identification of the cecal bacteria was performed by using selective and non-selective media. In the gastrectomized rats, the total bacterial count, and the counts of Bacteroidaceae and Enterobacteriaceae were higher than those in the sham-operated rats. Sc-FOS promoted an increase in the numbers of Bifidobacterium and Lactobacillus, In the rats fed on the Sc-FOS diet, the predominant type of bacteria was Lactobacillus and in the rats fed on the control diet, it was Bacteroidaceae irrespective of gastrectomy. We confirmed that both gastrectomy and dietary Sc-FOS changed the composition of cecal microflora in the rats. Dietary Sc-FOS in the gastrectomized rats increased the proportions of Lactobacillus relative to other types of bacteria to levels similar to those seen in healthy normal rats, and decreased the proportion of Bacteroidaceae.

Animals↗