Biomedical subjects
Publications and source records attributed to M Shimoda.
Lactobacillus brevis and Saccharomyces cerevisiae were completely sterilized by the supercritical (SC) CO2 micro-bubble method. Gaseous (G) and liquid (LQ) CO2 were used in a similar manner to compare the sterilizing effect. Among the three treatments, the microorganisms were only effectively sterilized by the SC CO2 treatment at 25 MPa and 35 degrees C.
Three siblings of a consanguineous parents with involuntary movements are reported. The mother had only a very slight neck tremor, without any other neurological abnormality, and the father had died. The 38-year-old son (Case 1) complained of involuntary movements at the age of 6. His involuntary movements were observed in the tongue, perioral region and upper and lower extremities: jerky movements with dystonic features. The 46-year-old elder brother (Case 2) experienced involuntary movements at the age of 18. Involuntary movements were observed in the upper extremities; he also had torticollis and tremulous movements in the neck, and jerky movements in the perioral region. They showed gait disturbance and dysarthria. The 35-year-old sister (Case 3) also experienced involuntary movements. When she was writing, her involuntary movements were obvious: dystonia and myoclonic jerks. Tremor in the neck was also seen. Their intelligence was below average. We concluded that this family had hereditary torsion dystonia, with myoclonus, and low intelligence. This condition may be associated with an autosomal recessive gene.
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The incidence of rerupture during the period of delayed ischemic neurological deficit (DIND) was studied in patients with aneurysmal subarachnoid hemorrhage (SAH) before surgical aneurysmal obliteration, and optimal management of DIND for preventing rerupture is discussed. At Tokai University Hospital, 511 patients with SAH were admitted during the 5-year period from 1988 to 1992. Of these, 247 had not undergone obliteration of the aneurysm neck within 3 days after SAH. In this group, 31% (77 patients) developed DIND. Of these 77 patients, 40 were managed with induced hypertension and/or hypervolemic therapy for DIND (25 with both (group 1), 15 with normotensive hypervolemic therapy (group 2)), and 37 did not receive either kind of therapy (group 3). The incidences of rerupture were as follows: all SAH patients: 11.5%; group 1: 48%; group 2: 7%; group 3: 11%. The incidence of rerupture in group 1 was significantly higher than that in the other groups. On the other hand, the favorable outcome rate (excellent and good) was as follows: group 1: 40%; group 2: 73%; group 3: 22%. This rate was significantly higher in patients who received normotensive hypervolemic therapy, than in other groups. This study suggests that, to avoid rerupture and unfavorable outcome, normotensive hypervolemic therapy is the optimal management approach in patients with DIND after SAH who have not undergone obliteration of the aneurysmal neck.
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Erythromycin (EM) pharmacokinetic variables were studied after IV administration of the drug (10 mg/kg of body weight) to 1-, 6-, and 15-day-old pigs. With advancing age, from 1 day to 15 days after birth, half-life of EM became shorter (3.0 hours to 1.4 hour), whereas apparent volume of distribution, total body clearance (CLt), and intrinsic clearance became greater: 0.68 to 3.28 (L/kg), 0.15 to 1.42 (L/h/kg), and 1.81 to 3.56 (L/h/kg), respectively. The percentage of plasma protein binding of EM decreased from 91 to 56%, correlating well with volume of distribution and CLt values. The altered binding percentage depended on plasma alpha 1-acid glycoprotein (AGP) concentration, but not on albumin concentration. With advancing age, plasma AGP concentration was markedly decreased from approximately 6,000 micrograms/ml to 700 micrograms/ml. Despite a twofold increase in intrinsic clearance with advancing age, CLt increased ninefold, implying that the decreased protein binding contributed to the increase of CLt more preferentially than did maturational development of elimination capacity. Therefore, the altered protein binding of EM attributable to the change in plasma AGP concentration could be a major causal factor of the age-related pharmacokinetic variables of EM in pigs.
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5,10-Methylenetetrahydrofolate (5,10-CH2-H4PteGlu) was identified as a major active reduced folate in rat bile using high-performance liquid chromatography with electrochemical detection (HPLC-ED). The identification of the folate derivative was based on the similarities in the retention-time profiles, electrochemical properties, UV absorption characteristics and demethylenation profiles of the bile folate and the synthetic standard. An HPLC-ED method was developed for the simultaneous determination of reduced folates including 5,10-CH2-H4PteGlu, tetrahydrofolate (H4PteGlu), 10-formyltetrahydrofolate (10-HCO-H4PteGlu) and 5-methyltetrahydrofolate (5-CH3-H4PteGlu) in rat bile. All peaks of the reduced folates in bile were separated using this method with a total retention time of less than 15 min. The detection limit was 0.01 ng/injection for H4PteGlu, 10-HCO-H4PteGlu and 5-CH3-H4PteGlu, and 0.02 ng/injection for 5,10-CH2-H4PteGlu at a signal-to-noise ratio of 3 and an injection volume of 100 microliters. Recoveries of synthetic folates from rat bile were higher than 90%. The distribution percentages of 5,10-CH2-H4PteGlu, H4PteGlu, 10-HCO-H4PteGlu and 5-CH3-H4PteGlu in rat bile were 29.6 +/- 7.2, 17.7 +/- 3.5, 24.4 +/- 6.5 and 28.2 +/- 7.1%, respectively, and total secretion rate of the bile reduced folates was 1514 +/- 663 ng/h (mean +/- S.D., n = 9).
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Sapecin is an antibacterial protein of the flesh fly and sapecin B is its homologue structurally similar to charybdotoxin of scorpion venom, which is known to be a K+ channel inhibitor. We found that, like charybdotoxin, sapecin B inhibits part of the voltage pulse-induced K+ currents of rat cerebellar Purkinje cells. We suggest that this effect is due to inhibition of the Ca(+)-activated K+ channel. Probably, sapecin B is a naturally occurring K+ channel inhibitor as well as an antibacterial protein.
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Cerebral haemodynamics were measured in 22 adult patients with secondary normal pressure hydrocephalus (NPH) before and after glycerol administration to determine which patients might benefit from a shunt procedure. Of these 22 patients, 14 were found to be shunt-responsive (group 1) and 8 were shunt-unresponsive (group 2). Measurement of regional cerebral blood flow (rCBF) was performed by xenon-enhanced computerized tomography (XeCT). Clinical factors such as the Evans' index and the presence or absence of brain atrophy, periventricular lucency (PVL), ventricular reflux, stagnation of cerebrospinal fluid on cisternography, and increased intracranial pressure were not statistically significant predictors of shunt responsiveness. Preoperative rCBF values did not differ between groups 1 and 2. The rCBF value in every cerebral region of group 1 patients increased significantly after shunting except for the basal ganglia. On preoperative rCBF measurement, all rCBF values in group 1 significantly increased after glycerol administration except for the periventricular lucency (PVL). Patients in group 2, however, lacked such an increase in rCBF. We therefore propose that, in patients with secondary NPH, shunt surgery will be likely to be effective in those with a demonstrated rise in rCBF after glycerol administration.
The effects of sound on the responses in teh abductor pollicis brevis muscle after magnetic cortical stimulation and on the H-reflexes in the wrist and finger flexor muscles were examined. Magnetic cortical stimulation and electrical stimulation eliciting H-reflexes were conditioned by sound stimulation. This sound stimulation did not produce the electromyographic response by itself. In the control subjects, sound stimulation produced an increase of the motor responses after cortical stimulation at intervals of 100, 150, 200 and 250 ms. The increase was greater in the patients with Parkinson's disease (PD). In the control subjects, sound stimulation produced an increase of the H-reflexes at intervals of 50, 100, 150 and 200 ms. This H-reflex increase in the PD patients was less than in the normal subjects. The reticular system might play a role in the abnormal motor control system in PD patients.
This study examined the effects of plasma alpha 1-acid glycoprotein (AGP) on the protein binding and pharmacokinetics of trimethoprim (TMP) in piglets. The piglets were given 5 mg/kg of TMP intravenously at 1, 14 and 28 days after birth. The plasma AGP level was highest at day 1. Fourteen days after birth, the level decreased by about 90% of that at day 1. The level at 28 days was almost the same as that at 14 days. Plasma protein bindings of TMP depended on the AGP level but not on the albumin level. The percentage of plasma protein binding decreased from 85 to 45%, and the AGP level also decreased from 6,000 to 700 micrograms/ml. The altered protein binding of TMP affected pharmacokinetic parameters such as total body clearance (CLtot), distribution volume and therefore the elimination rate constant. These parameters correlated well with the percentage binding to plasma proteins. Maturational development in the capacity to eliminate TMP was also indicated by the increase in total body clearance of unbound drug (CLtotub), which directly reflects the elimination capacity of the body. However, its contribution to the increase in CLtot was considered not to be large. CLtotub increased twofold 14 days after birth, whereas CLtot increased about ninefold. The increase in CLtot therefore, may result from both the maturational development in elimination capacity and the AGP-dependent decrease in plasma protein binding. It is concluded that the decrease in plasma AGP level observed in piglets is one of major factors affecting the pharmacokinetics of TMP.
After intravenous (1 mg/kg body weight), intramuscular (1 mg/kg body weight) and oral (1 and 50 mg/kg body weight) administration of folic acid (FA) to pigs, plasma levels of FA, tetrahydrofolic acid (THF), 5-methyltetrahydrofolic acid (5MF) were determined by using high-performance liquid chromatography. The pharmacokinetic profile of plasma FA after oral administration indicated an absorption rate-limited elimination, i.e., so called 'flip-flop' phenomenon. The bioavailability of FA was quite low after a high oral dose (F = 0.01), in contrast to a high value after intramuscular administration (F = 0.95). The plasma levels of biologically active, reduced forms of folates (THF and 5MF) were significantly increased over their basal levels after IV and IM administration to FA. The levels of these active folates were not increased after oral administration of a similar dose of FA. A 50 times higher dose was required to increase the active folates to the levels observed after IV and IM administration.
The aim of this study was to clarify the changes of inhibitory interneuronal activity in patients with chronic tension-type headache with disorder of pericranial muscle after treatment, and the pharmacological mechanisms of tizanidine--an alpha 2 adrenergic agonist. The effects of tizanidine on exteroceptive suppression (ES) of the temporalis muscle were examined in eighteen patients with chronic tension-type headache with disorder of pericranial muscles, before and two weeks after the administration of tizanidine. The left mental nerve was stimulated, under the maximal voluntary contraction of the temporalis muscles. Two types of stimulation were used: weak stimulation with four times the sensory threshold, and strong stimulation with 10 times the sensory threshold. The rectified electromyographic activity was recorded from the right temporalis muscle. ES2 produced by four times the sensory threshold was lengthened after tizanidine administration. This fact suggests that tizanidine improves the inhibitory function in the central nervous system, and then relieves headache. However, ES produced by 10 times the sensory threshold did not change. This suggests that the effect of tizanidine may be relatively mild. The interneurones mediating ES2 may be modified by the alpha 2 agonist.
This report describes an analytical method for the measurement of tetrahydrofolate (H4PteGlu), 10-formyltetrahydrofolate (10-HCO-H4PteGlu) and 5-methyltetrahydrofolate (5-CH3-H4-PteGlu) in rat bile by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). After diluting the bile sample with 0.2% sodium ascorbate solution, the sample was analyzed under the following conditions; (a) phenyl bonded phase column as an analytical column; (b) mobile phase consisting of 20 mM acetate buffer (pH 5.0) containing 0.1 mM EDTA; (c) an applied ECD potential of +300 mV; (d) 0.8 ml/min of flow rate. Under the above conditions, peaks of H4PteGlu, 10-HCO-H4PteGlu and 5-CH3-H4PteGlu in rat bile were well separated on the ECD-chromatogram. Detection limits of H4PteGlu, 10-HCO-H4PteGlu and 5-CH3-H4PteGlu were 0.13, 0.11 and 0.10 ng/ml, respectively, at S/N = 3. Bile excretion rates for H4PteGlu, 10-HCO-H4PteGlu and 5-CH3-H4PteGlu, which were analyzed by this method in rats, were 314 +/- 181, 321 +/- 179 and 449 +/- 198 ng/hr, respectively. Bile concentrations of the folates were more than 5,000 times higher than the detection limits for this method. This HPLC-ECD method is, therefore, a useful tool for bile folate analysis.
This report describes the clinico-pathological features of a group of 36 patients with malignant lymphoma of the central nervous system (CNS) who were treated at one institution between 1970 and 1993. All cases were B cell type lymphomas. The authors summarize the most salient findings with respect to clinical course, pathology, treatment and disease outcome, and emphasize the value of diagnostic and therapeutic modalities in the management of patients with primary CNS lymphoma.