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Biomedical subjects

M Takasaki

Publications and source records attributed to M Takasaki.

At least 109 records · Page 6Linked to original sources

[Longitudinal evaluation of early dementia of Alzheimer type using brain perfusion SPECT].

Regional cerebral blood flow (rCBF) measurements using a Patlak plot method of 99mTc-ECD were performed in early dementia of Alzheimer type (DAT) with both HDS-R and MMSE of over 20 to investigate initial abnormality and longitudinal changes of rCBF. A fusion technique of MRI and SPECT images was developed for MRI-guided analysis of regions of interest in hippocampal areas and statistical parametric mapping (SPM) was used for automated and objective approach to analysis of SPECT image data. Seventeen patients with clinically diagnosed early DAT and age-matched 32 normal control subjects were studied. At the first SPECT studies, the mean cerebral blood flow (mCBF) of 38.6 +/- 4.7 ml/100 g/min (mean +/- SD) for early DAT did not show significant reduction as compared with the normal control value of 42.0 +/- 3.8, whereas the rCBF values in the bilateral hippocampi (right; 26.8 +/- 4.7, left; 26.7 +/- 5.2) showed significant reduction (p < 0.05) as compared with the normal control values (right; 38.3 +/- 4.2, left; 38.4 +/- 3.8). The SPM analysis (voxel height; p < 0.001, Bonferroni correction; p < 0.05) of the first SPECT images revealed significant selective decrease of relative rCBF in the bilateral posterior cingulate gyri. At the second SPECT studies after 1.4 year on the average from the first studies, mCBF for early DAT showed a slight decrease by 1.7 +/- 3.8 ml/100 g/min/year. Bilateral hippocampi showed a greater decrease with slight left-side dominance by 3.8 +/- 3.3 on the right and 4.4 +/- 3.2 on the left side. The SPM analysis demonstrated significant decrease of relative rCBF in the basal fore-brain area, the left hippocampus, the left amygdala, and the left parahippocampal area. These results suggest that the MRI-guided ROI analysis of rCBF values in the hippocampus and the SPM analysis of SPECT images are quite useful for early diagnosis and follow-up of DAT.

Aged↗

[Chemotherapy with low-dose CDDP and continuous 5-FU for the treatment of advanced gastric cancers].

INTRODUCTION: 5-fluorouracil (5-FU) has been widely used for the treatment of gastrointestinal cancers. On the basis of recent findings, low-dose Cisplatin (CDDP) and continuous venous infusion of 5-FU have shown additive or synergistic antitumor effects in experimental models. We evaluated clinical effects of low-dose CDDP and 5-FU (low-dose FP therapy) in patients with advanced gastric cancers. PATIENTS AND METHODS: In December 1993 and June 1998, 52 patients with advanced gastric cancer were entered in this study. Patients were considered eligible if they had a bidimensionally measurable tumor. 5-FU (160 mg/m2/day) was continuously infused over 24 hours using an implantable port, and CDDP (3 mg/m2/day) was infused for half an hour. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest every four weeks according to response and tolerance. RESULTS: Low-dose FP therapy was given 44 patients (85%). The response rate was 65.9% and median survival time was 249 days. The responder group showed good survival compared with the non-responder group. The regimen was tolerable, and the most common toxicity was anorexia (40.3%). Three patients suffered from grade 3 anorexia, leukopenia and mucositis. On the other hand, renal dysfunction occurred in 50% (two of four patients administered over 1,000 mg CDDP). These results raise the possibility that the dose-limiting factor of low-dose FP therapy may account for the total dosage of CDDP. CONCLUSION: Low-dose FP therapy promises to be effective in the clinical management of advanced gastric cancer.

Adenocarcinoma↗

[Comparison of the effect of rapid infusion of lactated and that of acetated Ringer's solutions on maternal and fetal metabolism and acid-base balance].

The maternal and neonatal metabolism and acid-base balance were investigated in 20 parturients undergoing combined spinal and epidural anesthesia for cesarean delivery. Patients received intravenous infusion at a rate of either 25 ml.kg-1.h-1 of lactated (LR group, n = 10) or acetated (AR group, n = 10) Ringer's solution before anesthesia, to prevent hypotension during anesthesia. We obtained venous blood samples as follows; maternal control before anesthesia, maternal sample A after the infusion, umbilical sample B, and neonatal pedal sample C 5 h after birth, and determined lactate, pyruvate, bicarbonate, and base excess concentrations, and pH in each sample. In sample A, the lactate level was significantly higher and base excess level was significantly lower in the LR group than in the AR group. The pH of sample A and B was significantly higher in the AR group than in the LR group. However, no differences in all parameters of sample C between the two groups were observed. These results demonstrated that acetated Ringer's solution is better than lactated Ringer's solution in rapid infusion before cesarean section because of the correction of neonatal lactic acidosis.

Acid-Base Equilibrium↗

[Assessment of brain cell function using 123I-IMP SPECT of cerebral blood flow and visual evoked potential by photic stimulation in normal and demented elderly subjects].

Cerebral blood flow was quantitatively measured using 123I-IMP SPECT by photic stimulation and visual evoked potential (VEPs) in normal and dementia subjects: 8 with Alzheimer-type dementia, 9 with cerebrovascular dementia and 7 normal elderly subjects were divided into the three groups based on the Clinical Dementia Rating (CDR) grade: Group I (CDR 0), Group II (CDR 0.5-1), Group III (CDR 2-3). The 123I-IMP SPECT measurement was conducted at rest with the eyes closed and also during photic stimulation. VEPs were measured simultaneously. The results reveal prolongation of the P2 latency of the VEPs prolonged in accordance with the increasing severity of the dementia, and quantitative cerebral blood flow was lower in Group II and Group III than in Group I at rest, while during photic stimulation it significantly increased in Group I and II, but showed no change in Group III. The results suggest that quantitative measurement of cerebral blood flow using 123I-IMP SPECT by photic stimulation may enable more detailed assessment of brain cell function.

Aged↗

[Is hippocampal atrophy a specific change for Alzheimer's disease?].

Although detection of hippocampal atrophy has been proposed for the diagnosis of Alzheimer's disease (AD), atrophic changes in MRI can be found in other dementia diseases. This study was undertaken to determine whether hippocampal atrophy was a specific change for AD. Coronal T 1-weighted images were performed in 36 patients with AD, 40 patients with non-AD including vascular dementia, frontemporal dementia, Parkinson's disease with dementia, dementia with Lewy bodies, progressive supranuclear palsy, and normal pressure hydrocephalus, 9 patients with age-associated memory impairment (AAMI), and 24 control subjects. Hippocampal atrophy was graded subjectively on a 5-point scale. Scores of hippocampal atrophy for AD (2.11 +/- 0.95) and non-AD (1.80 +/- 0.91) were significantly higher than those for controls (0.79 +/- 0.72). Scores for AD were also significantly higher than those for AAMI (1.11 +/- 0.160), but no difference was found between AD and non-AD. These results suggest that hippocampal atrophy is not a specific marker for AD and appears to be a common phenomenon in dementia syndromes.

Aged↗

[Ambulatory and domiciliary cancer chemotherapy with forearm implant catheter system and low-dose CDDP + 5-FU therapy].

Shortening the period of hospitalizations and improving QOL attracting a great deal of attention in the field of medicine recently. Therefore, ambulatory and domiciliary treatment has become more important. This is not an exception in cancer therapy; the conversion from hospital treatment to ambulatory and domiciliary treatment is promoted. However, there is the danger of a lowered QOL as a resistant side effect, when the conventional cancer chemotherapy in the hospital is used as the ambulatory and domiciliary treatment. Recently, low-dose CDDP + 5-FU therapy (LFP therapy) that applies biochemical modulation has been developed for advanced gastrointestinal cancers. This therapy is thought to have a good antitumor effect and slight side effects, so it can be widely used. However, this therapy needs the continuous injection of 5-FU, so the hospital treatment was necessary, and ambulatory treatment was difficult with the usual administration method. Thus, we implanted a forearm central venous catheter system (forearm IVH reservoir), through which we can administer medication safely and conveniently without limiting the patient activity. LFP therapy was attempted in ambulatory and domiciliary treatment. Low-dose FP therapy consisted of 5-FU (160 mg/m2/day every day by continuous infusion) and cisplatin (3 mg/m2/day in 100 ml of normal saline by infusion over 30 minutes on days 1-5/W). Patients were treated for 4 consecutive weeks with a subsequent one-week rest period. The overall response rate was 52.1%. Grade 3 toxicity was observed in 5% of patients. An advantage was that in the ambulatory and domiciliary cancer chemotherapy the hematotoxicity was slight, and LFP therapy could be continued safely. In addition, it was also possible to attempt the improvement in QOL with the forearm IVH reservoir system. LFP therapy using the forearm IVH reservoir system may develop as a standard method of ambulatory and domiciliary cancer chemotherapy in the future.

Adult↗

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↗