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Biomedical subjects

M Takasaki

Publications and source records attributed to M Takasaki.

At least 19 recordsLinked to original sources

Regional differences in diffusion abnormality in cerebral white matter lesions in patients with vascular dementia of the Binswanger type and Alzheimer's disease.

We investigated changes in water diffusion in the cerebral white matter of 14 patients with vascular dementia of the Binswanger type (VDBT) and ten patients with Alzheimer's disease (AD) with periventricular hyperintensity (PVH) lesions using diffusion-weighted magnetic resonance imaging (MRI) and studied the pathophysiological differences between white matter lesions found in these two conditions. Apparent diffusion coefficients (ADCs) in the anterior and posterior white matter and the genu and splenium of the corpus callosum were significantly higher in both groups of patients than in the 12 age-matched controls, and ADC values in VDBT and AD groups were almost the same. ADC ratios, defined as diffusion restricted perpendicular to the direction of nerve fibers, were also significantly higher in the patients than in the control subjects. However, there were regional differences in ADC ratios in the two conditions, with ratios in VDBT being higher in the anterior portions of the white matter but ratios in AD were higher in the posterior portions. The diffusion-weighted MRI technique may be useful in the differential diagnosis of VDBT and AD with white matter lesions.

Aged

Differential effects of anesthetics on sympathetic nerve activity and arterial baroreceptor reflex in chronically instrumented rats.

The effects of pentobarbital sodium, chloralose, and urethane on sympathetic nerve activity and arterial baroreceptor reflex were examined using rats chronically instrumented for recordings of blood pressure (BP), electrocardiogram and renal sympathetic nerve activity (RSNA). Pentobarbital sodium (30 mg/kg, i.v.) produced a decrease in BP with a transient decrease in heart rate (HR) and no change in RSNA. Chloralose (50 mg/kg, i.v.) also caused a decrease in BP and no change in HR and RSNA until a later increase in HR and RSNA, while urethane (800 mg/kg, i.v.) increased BP, HR, and RSNA. Baroreceptor reflex function was assessed by constructing a logistic function curve compiled from data obtained by intravenous infusion in increasing doses of phenylephrine and sodium nitroprusside. Both pentobarbital sodium and chloralose administration decreased the gain of baroreceptor reflex control of both HR and RSNA. Urethane also decreased the gain of baroreceptor reflex control of HR but elicited no change in that of RSNA. These results suggest that different intravenously administered anesthetics affect the peripheral sympathetic outflows in qualitatively and quantitatively different manners.

Anesthetics

Cancer chemopreventive activity of synthetic colorants used in foods, pharmaceuticals and cosmetic preparations.

In continuation with our studies to uncover cancer chemopreventive effects of non-toxic natural colorants and other products of biologic and synthetic origin, we tested several Food and Drug Administration-approved synthetic colorants for antitumor promoting potential by the in vitro Epstein-Barr virus early antigen activation in Raji cells in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Among 29 such colorants used in foods, pharmaceuticals and cosmetics and evaluated in vitro, six of the 10 most effective had an azo group. Three structurally unrelated colorants tested in this assay were also studied in vivo for chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced TPA-promoted mouse skin carcinogenesis. The results indicate that tartrazine, indigo carmine and erythrosine are potent inhibitors of skin tumor promotion in mice treated with DMBA and TPA.

9,10-Dimethyl-1,2-benzanthracene

Diffusion-weighted MR imaging of the hippocampus and temporal white matter in Alzheimer's disease.

We investigated the changes in water diffusion in the hippocampus and the temporal white matter (the temporal stem) in eight patients with possible Alzheimer's disease (AD), 10 patients with probable AD, and 10 age-matched controls, using coronal diffusion-weighted magnetic resonance (MR) imaging. Apparent diffusion coefficients (ADCs) were derived for the three orthogonal axes and an index of diffusion anisotropy (IDA = ADC(max-min)/ADC(mean)) was then calculated. Although no significant differences were found in ADC and IDA values in the hippocampal body between controls and patients, vertical (superior-inferior) ADC values and ADC(mean) values in the temporal stem of patients with AD were significantly higher than those in controls, and IDA values were therefore significantly lower in patients with possible or probable AD than those in controls. Moreover, IDA values in the temporal stem were significantly correlated with the clinical severity. These results suggest that decreased fiber density, such as the disruption and loss of axonal membranes or myelin, occur early in the temporal stem, probably due to secondary degeneration related to grey matter pathology including the medial temporal lobe.

Aged

Effects of anesthetics on norepinephrine release in the hypothalamic paraventricular nucleus region of awake rats.

The effects of pentobarbital sodium, chloralose and urethane on norepinephrine (NE) release in the hypothalamic paraventricular nucleus (PVN) region were examined in awake rats. An in vivo microdialysis method was used. Extracellular NE concentrations in the PVN region were measured by high performance liquid chromatography with electrochemical detection. Pentobarbital sodium (30 mg/kg, intravenously [i.v.]) and chloralose (50 mg/kg, i.v.) caused a 30-40% decrease in NE release while urethane (800 mg/kg, i.v.) caused a 50% increase. Plasma NE concentration was not altered after pentobarbital sodium and chloralose administrations, except for its increase in chloralose at 5 h, while the concentration increased significantly (P < 0.01) after urethane. These results suggest that, in the rat, these anesthetic agents have different effects on noradrenergic activity in the PVN region as well as on plasma NE.

Anesthetics

Haemodynamic effects of induction of general anaesthesia with propofol during epidural anaesthesia.

PURPOSE: To clarify whether propofol administration during thoracic or lumbar epidural anaesthesia intensifies the haemodynamic depression associated with epidural anaesthesia. METHODS: Patients (n = 45) undergoing procedures of similar magnitude were randomly divided into three study groups: a control group (n = 15) receiving general anaesthesia alone and two study groups undergoing thoracic (n = 15) and lumbar epidural anaesthesia (n = 15) before induction of general anaesthesia. All patients received 2 mg.kg-1 propofol at a rate of 200 mg.min-1, followed by a continuous infusion of 4 mg.kg-1.hr-1. Mean arterial blood pressure (MAP) and heart rate (HR) were measured at baseline, three minutes after induction, and one minute after tracheal intubation in all three groups and at 20 min after epidural anaesthesia was established in the thoracic and lumbar groups. RESULTS: Following epidural anaesthesia, MAP decreased from 94 +/- 14 (SD) at baseline to 75 +/- 11 mmHg (P < 0.0001) in the thoracic group and from 92 +/- 12 to 83 +/- 15 mmHg in the lumbar group. After propofol administration, MAP decreased further in the thoracic group to 63 +/- 9 mmHg (P = 0.0077) and to 67 +/- 10 mmHg (P = 0.0076) in the lumbar group. The MAP following propofol induction in the thoracic group (P < 0.0001) and in the lumbar group (P = 0.0001) was lower than MAP in the control group (81 +/- 9 mmHg). HR decreased only in response to thoracic epidural anaesthesia (P = 0.0066). CONCLUSION: The hypotensive effects of propofol are additive to those of epidural anaesthesia, resulting in a profound decrease in mean arterial pressure.

Analysis of Variance

Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals.

The telomerase activity and length of telomeres of peripheral blood mononuclear cells obtained from 124 healthy individuals aged 4-95 years was measured. Telomerase activity level was semiquantitatively assessed by a fluorescent-telomeric repeat amplification protocol (fluorescent-TRAP) using an internal telomerase assay standard, fluorescent primers and an automated laser fluorescent DNA sequencer. Telomeric length, measured by assay of terminal restriction fragments (TRFs), was determined in HinfI-digested DNA by Southern blot analysis using a (TTAGGG)4 probe. TRF length was determined in 80 individuals and age-related progressive reduction of size was observed. TRF length in peripheral blood mononuclear cells obtained from normal individuals (aged 4-39 years) decreased by approximately 84 bp per year, while in individuals aged > or = 40 years it decreased by 41 bp per year. In contrast, telomerase activity showed an apparent biphasic pattern with aging. Individuals aged 4-39 years showed a progressive decrease in telomerase activity, whereas 65% of those aged > or = 40 years showed relatively stable but very low telomerase activity, and the remaining individuals aged > or = 40 years had no detectable telomerase activity. These data obtained from normal individuals might in the future be of value to help risk stratify and manage the care of patients with leukemia.

Adolescent

New glycosides from ajuga decumbens

A new phenethyl alcohol glycoside, galactosylmartynoside (1), and a new abietatriene-type diterpene glycoside, ajugaside A (2), were isolated from the whole plants of Ajuga decumbens, together with known phenethyl alcohol glycosides (3 and 4) and iridoid glycosides (5-7). Chemical structures were elucidated on the basis of spectral data. Of these compounds, 8-acetylharpagide (6) exhibited the strongest inhibitory effect on Epstein-Barr virus activation induced by 12-O-tetradecanoylphorbol-13-acetate.

Journal Article

Sarcoidosis induced by interferon therapy for chronic myelogenous leukaemia.

A 31-year-old male was diagnosed as having chronic myelogenous leukaemia and has been treated with hydroxyurea and interferon-alpha since February 1995. After 16 months, he complained of low-grade fever and a cough. Bilateral hilar lymph node enlargement was detected on the chest X-ray film and multiple subcutaneous erythematous nodules appeared. A skin biopsy revealed subcutaneous sarcoid granuloma. Two months after the cessation of interferon therapy, the subcutaneous nodules and the hilar lymph node enlargement resolved. It is possible that continuous interferon administration can promote granuloma formation in sarcoidosis by activating T cells and macrophages.

Adult

Three-dimensional development of bovine reticular cell (Cellula reticuli).

This paper describes the three-dimensional construction of the reticular cell, cellula reticuli, in bovine reticulum and its ontogenetic development. Reticular cells of fetal suckling calf and adult tissues were investigated both at the surface of intact mucosa and macerated samples using scanning electron microscopy. At the third month of gestation, the formation of the reticular cells on the mucosal surface started from the center of the cell and just above the reticular crest. The reticular crests were observed on the surface of the macerated sample at an earlier period of gestation (third month). In the eighth month of gestation, primary, secondary and tertiary reticular crests and papillae could be observed from the mucosal surface. Macerated samples showed that those structures were already formed completely under the epithelium by the first half of the seventh month of gestation. It is suggested that the development of the reticular papillae starts from the lower to the upper parts of the reticular cell.

Age Factors

Graded, irreversible changes in crayfish giant axon as manifestations of lidocaine neurotoxicity in vitro.

UNLABELLED: High concentrations of lidocaine induce irreversible conduction block with little effect on resting membrane potential (Em). We assumed the mechanism of persistent neurologic deficit caused by local anesthetics may result from neural death, as represented by the loss of Em. We investigated the effects of lidocaine on Em and action potential (AP) in single crayfish giant axons in vitro. Axons were perfused with two doses of lidocaine for either 15 or 30 min, and they were continuously washed. No axons exposed to 80 mM lidocaine for 30 min showed recovery of AP and Em. Those exposed to 40 mM for 30 min and 80 mM for 15 min showed a return to baseline for Em, but no recovery of AP. Those exposed to 40 mM lidocaine for 15 min showed full recovery of Em and AP immediately after washing. The membrane depolarization was significantly greater during exposure to 80 mM lidocaine for 30 min than in other groups. We conclude that lidocaine has a direct neurotoxic effect on crayfish giant axons and that the generation of AP is more vulnerable than the maintenance of Em. The irreversibility of AP and Em is dose- and time-dependent. IMPLICATIONS: Highly concentrated lidocaine induced an irreversible conduction block and a complete loss of resting membrane potential in crayfish giant axons in vitro. Our results may represent a possible explanation for various grades of local anesthetic-induced neurotoxicity in clinical cases if the same toxicity occurs in mammalian nerves in vivo.

Action Potentials

The effects of extracellular pH with and without bicarbonate on intracellular procaine concentrations and anesthetic effects in crayfish giant axons.

BACKGROUND: The potentiating effect of sodium bicarbonate on local anesthetic action is attributed to two mechanisms: (1) an increase in the un-ionized local anesthetic due to extracellular alkalinization, and (2) an accelerated conversion of local anesthetic from un-ionized to ionized form with intracellular acidification caused by bicarbonate. To evaluate these hypotheses, the intracellular pH, intracellular ionized procaine concentration, and evoked action potentials were measured in crayfish giant axons. METHODS: In all measurements, axon preparations from crayfish were perfused extracellularly for 15 min with either bicarbonate-containing solution at pH 7.6 (bicarb/7.6) or bicarbonate-free solution at pH 7.6 (nonbicarb/7.6) or pH 8.0 (nonbicarb/8.0). Intracellular pH was measured using a pH-sensitive microelectrode. Intracellular anesthetic concentration was measured using a specially designed procaine-sensitive microelectrode with each of three solutions containing 1 mM procaine hydrochloride. Membrane potential was measured and, as an index of anesthetic action, the dV/dt of evoked action potential was calculated during perfusion with procaine. RESULTS: Mean intracellular pH was significantly lower in the bicarb/7.6 (7.16+/-0.07) group than in the nonbicarb/7.6 (7.33+/-0.09) and nonbicarb/8.0 (7.33+/-0.12) groups (P < 0.01). The mean intracellular ionized procaine concentration was significantly higher in the bicarb/7.6 (0.53+/-0.08 mM; P < 0.05) and nonbicarb/8.0 (0.58+/-0.13 mM; P < 0.01) than in nonbicarb/7.6 (0.32+/-0.14 mM) group but did not differ between the bicarb/7.6 and nonbicarb/8.0 groups. The mean percentage decrease in dV/dtmax was approximately coincident with the mean intracellular procaine concentration in each solution. CONCLUSION: The presence of bicarbonate or extracellular alkalinization increased the intracellular concentration of ionized procaine and the anesthetic effect.

Action Potentials

A study of peripheral airway findings using an ultrathin bronchofiberscope and bronchoalveolar lavage fluid with diffuse panbronchiolitis.

We investigated the peripheral airways using an ultrathin bronchofiberscope and analyzed bronchoalveolar lavage fluid (BALF) in 10 patients with diffuse panbronchiolitis (DPB; refractory and responsive to treatment with macrolide antibiotics) and 10 healthy volunteers. Refractory DPB patients had obstruction at the 11th or 12th level of bronchial branches and secretion from the 5th to 6th order bronchi to the 11th-12th level of bronchial branches. In responsive DPB patients, there was no obstruction of peripheral airways, but secretion in the bronchial lumens still remained in nearly all observed bronchial branches. Despite macrolide therapy, BALF from patients with refractory DPB contained a high percentage of neutrophils and had a lower CD4/CD8 ratio. Two-color analysis of T cell subsets in BALF revealed a high percentage and number of CD8+S6F1+ cells (activated cytotoxic T cells) in refractory DPB patients. Our findings suggest that obstruction around the terminal bronchioles may be correlated with BALF abnormalities and may be irreversible despite macrolide therapy in progressive DPB.

Adult

Anti-tumor-promoting activity of majonoside-R2 from Vietnamese ginseng, Panax vietnamensis Ha et Grushv. (I).

Seven saponins (1-7) isolated from the rhizomes and roots of Panax vietnamensis were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in Raji cells as a primary screening test for anti-tumor-promoters (cancer chemopreventive agents). The ocotillol-type saponin, majonoside-R2 (2), which is the major and characteristic constituent of this plant, exhibited a significant inhibitory effect on EBV-EA activation. Furthermore, the cell cycle analysis of 2 on Raji cells was also examined and strong inhibition was observed on the effect of the cell cycle induced by TPA. Compound 2 showed potent anti-tumor-promoting activity in two-stage carcinogenesis tests of mouse skin using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA or fumonisin B1 as a promoter. Consequently, these results suggest that majonoside-R2 (2) could be a valuable chemopreventive agent against chemical carcinogenesis.

Animals

Anti-tumor-promoting activity of diterpenes from Excoecaria agallocha.

To search for possible anti-tumor-promoters, we carried out the primary screening of seventeen diterpenes (1-17) isolated from the resinous wood of Excoecaria agallocha (Euphorbiaceae) using an in vitro synergistic assay system. Of these diterpenes, ent-16-hydroxy-3-oxo-13-epi-manoyloxide (5), (13R,14R)-ent-8alpha,13;14,15-diepoxy-13-epi- labda-3beta-ol (8) ent-3beta-hydroxy-15-beyeren-2-one (10) and ent-15-hydroxy-labda-8(17),13E-dien-3-one (14) exhibited significant inhibitory effects on Epstein-Barr virus (EBV) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, 10 exhibited remarkable anti-tumor-promoting activity in vivo on a two-stage carcinogenesis test of mouse tumor using 7,12-dimethylbenz[a]-anthracene (DMBA) as an initiator and TPA as a promoter.

9,10-Dimethyl-1,2-benzanthracene

Dissociation of adrenomedullin concentrations in plasma and cerebrospinal fluid in pregnant and non-pregnant women.

Adrenomedullin (AM), a potent vasodilator peptide, has been shown to act within the central nervous system to modulate fluid and electrolyte balance. AM-immunoreactive cells have been found in the anterior pituitary gland and the choroid plexus of humans. In addition, AM activity has been implicated in the regulation of maternal circulation during pregnancy. To determine the relationship between AM concentration in the cerebrospinal fluid (CSF) and plasma, we measured AM levels in CSF and plasma of pregnant (group P, n = 12) and non-pregnant (group NP, n = 10) women scheduled to undergo gynecologic or obstetric surgery. In both groups, the concentration of AM in the plasma exceeded that in the CSF. Plasma AM concentration was significantly higher in pregnant than non-pregnant women (17.3+/-5.8 vs 5.1+/-1.4 pmol/l, mean +/- S.D.; P<0.01), whereas CSF AM concentration did not differ between the two groups (1.3+/-0.9 and 0.9+/-0.4 pmol/l in groups P and NP respectively). No significant correlation was found between AM concentrations in the CSF and plasma. The present findings suggest that AM is present in the CSF and that its concentration in the CSF is regulated independently from that in the plasma.

Adrenomedullin

Diffusion-weighted magnetic resonance and magnetization transfer imaging in the assessment of ischemic human stroke.

We compared characteristic features in ischemic stroke lesions from the hyperacute to the chronic stage on diffusion-weighted (DW) and magnetization transfer (MT) images with those on T2-weighted (T2W) images, and assessed changes in apparent diffusion coefficient (ADC), MT effect (MTe), and T2 ratios (infarct/normal) over time. DW images were particularly useful for detecting hyperacute infarcts within 6 hours of onset and in distinguishing acute lesions from chronic lesions. ADC ratios were lower within 7 days after onset and rose toward 1.0 in the subacute phase, becoming relatively isotense on ADC maps, but elevated thereafter. Although MTe ratios were unchanged or only subtly changed in the acute stage, they became significantly lower in the subacute and chronic stages. These combined magnetic resonance (MR) techniques were useful in the assessment of ischemic stroke and facilitated the determination of the age of cerebral infarct.

Aged