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Biomedical subjects

M Machida

Publications and source records attributed to M Machida.

At least 109 records · Page 6Linked to original sources

[Functional diagnosis of brachial plexus injuries].

We evaluated 10 patients with verified brachial plexus injuries and root avulsion. In 100%, dermatomal somatosensory evoked potentials (DSSEPs) were abnormal. Compound muscle action potentials (CMAPs) by magnetic stimulation revealed 90% abnormal findings on the affected side, but also revealed abnormality in adjacent segments. Dissociation of CMAPs and DSSEPs revealed the apparent continuity of motor and sensory nerves. The use of both techniques for the examination of the function of proximal peripheral nerve revealed increased latencies over the motor and/or sensory pathways in all patients. The technique of non-invasive stimulation of the motor pathway therefore provides an additional tools to detect and quantify subclinical and clinically apparent lesions in patients with defined brachial plexus injuries and root avulsions.

Action Potentials↗

Toxicokinetic study of norfloxacin-induced arthropathy in juvenile animals.

A toxicokinetic study of norfloxacin-induced arthropathy in juvenile animals was undertaken using nalidixic acid as a standard drug. Norfloxacin and nalidixic acid were subcutaneously administered to rats and rabbits, orally administered to dogs, and norfloxacin was orally dosed to monkeys once a day for 7 consecutive days. Of the dose levels tested, the minimum arthropathic doses of norfloxacin were 100, 25, and 50 mg/kg/day in rats, rabbits, and dogs, respectively. At these doses, the peak serum concentrations (Cmax) on Day 6 were 16.1, 9.73, and 5.11 micrograms/ml, and the areas under the serum concentration/time curve (AUC0----infinity) were 31.9, 22.9, and 26.2 micrograms.hr/ml, in respective animals. Monkeys showed no arthropathy with norfloxacin at doses of less than 500 mg/kg/day, at which the Cmax and AUC0----infinity were 15.6 micrograms/ml and 103 micrograms.hr/ml, respectively. The minimum arthropathic doses of nalidixic acid were 50, 100, and 25 mg/kg/day in rats, rabbits, and dogs, respectively. The Cmax and AUC0----infinity of nalidixic acid were higher than those of norfloxacin in all animals. Joint tissues took up more norfloxacin than nalidixic acid, but when arthropathy was present the articular cartilage concentrations of the two drugs were in the same range. The penetration of norfloxacin into the articular cartilage was the same regardless of the joint's anatomical locations, but differed among species, being highest in rats and lowest in monkeys. The Cmax and AUC0----infinity of norfloxacin in animals at their arthropathic doses were far higher than those measured clinically in children, whereas those of nalidixic acid in animals did not differ much from its clinical parameters.

Administration, Oral↗

New lidocaine ester derivatives with a prolonged anesthetic effect.

In order to find a new long acting local anesthetic, methyl, ethyl, and butyl ester derivatives of lidocaine were synthesized in our laboratory. The topical anesthetic activity was studied with the effects on corneal reflex in rabbits, and the duration of action with those on the action potential of rabbit vagus nerve was studied in vitro. All drugs showed adequate topical anesthetic activities. The onset time to induce a complete blockage of the action potential in the excised vagus nerve was 97.1 +/- 6.3 s for lidocaine, 289.3 +/- 29.0 s for methyl ester, 186.3 +/- 18.4 s for ethyl ester, and 85.3 +/- 9.0 s for butyl ester. The mean duration of action, which was assessed as the time to recover from the complete block to 30% of control amplitude in a drug-free medium, was 32.5 +/- 3.1 min for lidocaine, 39.9 +/- 11.3 min for methyl ester, 68.2 +/- 4.2 min for ethyl ester, and 108.7 +/- 12.3 min for butyl ester. The differences in the duration of action between the ester derivatives and the original lidocaine were all statistically significant. The duration of action of all drugs studied paralleled with their protein binding capacities. These findings indicate the possibility that the ester derivatives studied, especially butyl ester, can be used as a long acting local anesthetic.

Journal Article↗

Effect of spinal cord ischemia on compound muscle action potentials and spinal evoked potentials following spinal cord stimulation in the dog.

We recorded the compound muscle action potentials (CMAP) from the soleus muscle and spinal evoked potentials (SpEP) from the caudal spinal cord after stimulation of the rostral spinal cord via epidural electrodes in 18 dogs. We examined the changes of CMAP and SpEP after the cord was made ischemic by clamping the aorta at different levels. Clamping the abdominal aorta below the artery of Adamkiewicz (five dogs) did not change either CMAP or SpEP significantly. When the thoracic aorta was clamped above the radicular and Adamkiewicz arteries (10 dogs), CMAP disappeared entirely within 5-10 min of occlusion, but SpEP showed only minimal latency prolongation limited to the late peaks in seven of 10 dogs. In the remaining three dogs, both CMAP and SpEP disappeared within 30 min of occlusion but with the more rapid deterioration of CMAP than of SpEP. Progressive ligation of lumbar arteries (three dogs) from caudal to rostral levels did not change CMAP until ligation of Adamkiewicz artery. Then CMAP disappeared, but SpEP remained unchanged. These findings suggest that CMAP and SpEP are mediated through different pathways and that CMAP reflect anterior cord function. The described electrophysiologic technique would be useful to monitor spinal cord motor function during surgery of the spine, spinal cord, or thoracoabdominal aorta.

Action Potentials↗

[Electrophysiological diagnosis in ulnar nerve entrapment at elbow].

Using "inching technique" we recorded antidromic sensory nerve action potentials from the little finger and compound muscle action potentials from the abductor digiti minimi, first dorsal interosseous and flexor carpi ulnaris muscles in 30 entrapped ulnar nerves. In cubital tunnel syndrome, localized conduction delay occurred most commonly at a point 2 to 4 cm distal to the medial epicondyle. In other ulnar neuropathies, with the exception of cubitus valgus deformity, conduction block or delay was noted at a site just distal to the medial epicondyle. These conduction abnormalities were most commonly observed in the abductor digiti minimi and first dorsal interosseous. In contrast, conduction abnormality in tardy palsy secondary to the valgus deformity reflected mainly in the flexor carpi ulnaris. This method provides useful information in diagnosing the early involvement and precise localization of nerve entrapment, and differentiation of cubital tunnel syndrome from other ulnar nerve entrapment.

Action Potentials↗

Purification and characterization of a nuclear factor which binds specifically to the upstream activation sequence of Saccharomyces cerevisiae enolase 1 gene.

The nuclear factor which specifically binds to the upstream activation sequence (UAS) of the enolase 1 gene (ENO1) of yeast Saccharomyces cerevisiae was purified by sequence-specific affinity chromatography. The purified factor gave two closely migrated bands at 32 kDa on SDS/PAGE. The binding activities were eluted from a gel filtration column at molecular masses of 110 kDa and 60 kDa, suggesting a dimeric and a tetrameric assembly of the factor in the native form. The region protected by the purified factor against deoxyribonuclease I digestion contained the sequence ACCCAAACACC which is highly similar to the consensus sequence present in the 5'-flanking region of the ribosomal protein genes (RPG box). We also identified the other factor specific to the ENO1 UAS which gave a single peak at a molecular mass of 120 kDa in gel filtration. We suggest the existence of multiple binding to the ENO1 UAS by at least two factors: one is the factor which we purified with a molecular mass of 32 kDa on SDS/PAGE and the other is the factor like RAP1 protein which generally recognizes the RPG-box-like sequence.

Base Sequence↗

Compound muscle action potentials and spinal evoked potentials in experimental spine maneuver.

In this study, the authors evaluated the effects of spine manipulations, similar to those used in scoliosis surgery, on the compound muscle action potential (CMAP) and spinal evoked potential (SEP) in 25 cats: a distraction maneuver was performed in ten, a rotation in five, and a combined (distraction and rotation) procedure in ten cats. Compound muscle action potential was only minimally changed by the rotation maneuver alone in all five cats. Distraction resulted in earlier deterioration of CMAP than SEP; when CMAP was no longer elicitable in ten cats, seven still showed measurable SEP. All ten cats became paraplegic. With the combined procedure, both CMAP and SEP were abolished earlier than with distraction alone. This was observed in all ten cats becoming paraplegic. The authors further extended the study to ten rabbits having experimentally induced scoliosis. Following corrective surgery with distraction and derotation, eight rabbits lost both CMAP and SEP. Two lost CMAP with still recordable SEP. All ten rabbits became paraplegic. These findings suggest that monitoring CMAP is a more sensitive measure than SEP, and that the spinal cord is more vulnerable to a combined distraction and derotation maneuver than to either one alone.

Action Potentials↗

[Bolus and maintenance infusion of high-dose methotrexate].

For 17 patients with bone and soft tissue sarcoma, 32 bolus and maintenance infusions of high-dose methotrexate (MTX) were performed to induce rapid elevation of plasma MTX concentration and to maintain it. At the doses of 200-300 mg/kg, plasma MTX concentrations were measured by enzyme assay. It needed four hours to reach the steady state by five hours' constant rate infusion, with the plasma plateau concentration at about 1 X 10(-3) M/L. On the other hand, bolus infusion of MTX needed only one hour to reach over 5 X 10(-4) M/L, and the plateau concentration lasted during the maintenance infusion period. By the constant rate infusion as well as bolus infusion, it was possible to maintain the plasma concentration over 1 X 10(-4) M/L for 12 hours, but both infusions can not maintain 1 X 10(-3) M/L for a long time. From these results, clinical effects of high dose MTX against sarcomas seemed to be evaluated by the plasma MTX plateau concentration and the maintenance time.

Bone Neoplasms↗

The protein factor which binds to the upstream activating sequence of Saccharomyces cerevisiae ENO1 gene.

Using a gel retardation assay it was shown that the 87 bp DNA fragment (UAS87) containing the upstream activating sequence (UAS) of S. cerevisiae EN01 gene and a nuclear extract gave rise to three migration-retarded species specific to UAS87. Heat- or proteinase-treatment of the nuclear extract revealed that these species were protein-DNA complexes. The precise binding region of the protein identified by DNaseI protection analysis was found to include a CCAAACA sequence which forms a dyad-symmetrical structure. The amount of one of the three migration-retarded species significantly increased when cells were grown in medium containing a gluconeogenic carbon source. The introduction of pGCR8, a multicopy plasmid containing GCR1 gene, a regulatory gene controlling the expression of several glycolytic enzymes, showed no effect on the amount of three migration-retarded species.

Base Sequence↗

Effect of desynchronized inputs on compound sensory and muscle action potentials.

Stimulation of the second (S1) or third (S2) digit elicits a median sensory potential at the wrist. Similarly, a shock applied to the median (Sm) or ulnar (Su) nerve at the wrist evokes a sensory potential of the fourth digit and a muscle potential over the thenar eminence. Hence, a concomitant application of S1 and S2 or Sm and Su with varying interstimulus intervals simulates the effect of desynchronized inputs. In 10 hands, a shift in latency on the order of 1 msec between S1 and S2 or Sm and Su caused a major reduction in sensory potential by as much as 30-40% but little change in muscle action potential. A latency difference slightly less than one-half the total duration of unit discharge maximized the phase cancellation between the two components and consequently the loss of area under the waveform.

Action Potentials↗

Dissociation of muscle action potentials and spinal somatosensory evoked potentials after ischemic damage of spinal cord.

In patients undergoing spinal fusion and Cotrel-Dubousset instrumentation we recorded compound muscle action potentials (CMAP) from the lower limb and spinal somatosensory evoked potentials (SSEP) from the caudal epidural space after direct stimulation of rostral spinal cord via epidural electrodes. In three of 30 patients tested, the derotation maneuver altered CMAP but not SSEP. In ten dogs, we observed similar dissociation with decrease or disappearance of CMAP amplitude and unchanged SSEP after ligation of the thoracoabdominal aorta or intercostal arteries at each level. In contrast, both CMAP and SSEP were unchanged by clamping the artery at the lumbar level. This is likely due to the lack of collateral vascular flow at the thoracic cord level, the anterior cord in particular, which is mainly supplied by a single large radicular artery (Adamkiewicz artery). These findings support that the CMAP and SSEP are mediated through two independent pathways located in the anterior and posterior spinal cord, respectively. We postulate that the dissociate alteration of CMAP and SSEP by derotation maneuver is due to greater vulnerability of the anterior cord or motor tract to ischemia caused by the displacement of anterior spinal or radiculomedullary artery. Therefore, the patients requiring major derotation procedure would benefit from CMAP monitoring, which provides more sensitive measure of anterior cord function that the conventional SSEP monitoring.

Action Potentials↗

Nucleotide sequences of Saccharomycopsis fibuligera genes for extracellular beta-glucosidases as expressed in Saccharomyces cerevisiae.

We isolated two genes for extracellular beta-glucosidase, BGL1 and BGL2, from the genomic library of the yeast Saccharomycopsis fibuligera. Gene products (BGLI and BGLII) were purified from the culture fluids of Saccharomyces cerevisiae transformed with BGL1 and BGL2, respectively. Molecular weights of BGLI and BGLII were estimated to be 220,000 and 200,000 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The two beta-glucosidases showed the same enzymatic characteristics, such as thermo-denaturation kinetics and dependencies on pH and temperature, but quite different substrate specificities: BGLI hydrolyzed cellobiose efficiently, but BGLII did not. This result is consistent with the observation that the S. cerevisiae transformant carrying BGL1 fermented cellobiose to ethanol but the transformant carrying BGL2 did not. Southern blot analysis revealed that the two beta-glucosidase genes were derived from Saccharomycopsis fibuligera and that the nucleotide sequences of the two genes are closely related. The complete nucleotide sequences of the two genes were determined. BGL1 and BGL2 encode 876- and 880-amino-acid proteins which were shown to be highly similar to each other. The putative precursors begin with hydrophobic segments that presumably act as signal sequences for secretion. Amino acid analysis of the purified proteins confirmed that BGL1 and BGL2 encode BGLI and BGLII, respectively.

Amino Acid Sequence↗

[Urinary beta 2-microglobulin as an indicator for impaired excretion of methotrexate].

Twenty cases treated with high-dose methotrexate (MTX) infusions were studied to determine whether urinary beta 2-Microglobulin (beta 2-M) is a reliable indicator to predict impaired excretion of methotrexate. Before and after MTX infusions, the levels of urinary beta 2-M were measured along with serum creatinine, uric nitrogen, and creatinine clearance. MTX clearance was found to be impaired in four of the 20 infusions, although concentrations of serum creatinine and uric nitrogen, and creatinine clearance were normal prior to the infusions. In the four cases that resulted in impaired excretion, a significant increase of beta 2-M levels was noted before and after the high-dose MTX infusion (p less than 0.01). Although one of the four cases showed a normal level of beta 2-M before the infusion, the post-infusion level of beta 2-M extremely high. This raised level of beta 2-M was thought to be caused by impaired excretion due to decreased amounts of urine. We conclude that urinary beta 2-M is a sensitive indicator of impaired excretion of high-dose MTX infusion, and especially when levels of more than 250 ng/ml of urinary beta 2-M are found to exist, it seems to difficult to clear the drug following high-dose MTX treatment.

Blood Urea Nitrogen↗

Monitoring of motor action potentials after stimulation of the spinal cord.

We recorded motor action potentials in cats, using surface electrodes placed over the soleus muscle. The action potentials were generated by stimulating the spinal cord with electrodes in the epidural space at the level of the fifth or sixth thoracic vertebra. This also was done in humans, using the same methods of stimulating and recording, but the intensity of the stimulus was adjusted to produce little or no twitch of the paraspinal muscles. In the animal experiment, the motor action potential was abolished after transection of the pyramidal tract and was progressively attenuated with effective doses of a curare-like agent. We also tested the effect of distraction, using the same technique as is used in Harrington instrumentation, and found that the amount of distraction that caused reduction of the amplitude of the motor action potential of more than 50 per cent, when sustained for longer than seven minutes, caused permanent paraplegia in two cats. The evaluation of spinal evoked potentials that were obtained from epidural electrodes placed caudad to the level of distraction, and of motor action potentials that were recorded over the soleus muscle, following the same stimulus, showed a similar pattern of reduction after distraction in five of seven cats. The other two cats had irreversible reduction of motor action potential associated with unchanged spinal evoked potential, and both cats became paraplegic.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

A positive regulatory sequence of the Saccharomyces cerevisiae ENO1 gene.

ENO1-'lacZ fusions with various lengths of the ENO1 5'-flanking region were constructed on various types of yeast plasmid vectors. The fully expressed level of beta Gal directed by ENO1-'lacZ fusions differed depending on the type of vector, but on any type of vector, beta Gal activity was not greatly influenced by the carbon source in the medium. The 86-bp DNA region of ENO1 at position -487 to -402 upstream of the initiation codon, in which we had previously delimited the positive regulatory region of ENO1 (Uemura, H., Shiba, T., Paterson, M., Jigami, Y., & Tanaka, H. (1986) Gene 45, 67-75), exerted its function without requiring precise location with respect to the TATA box. The action of the positive regulatory region was not affected by its orientation. In addition, the substitution of the UASs of PHO5, encoding repressible acid phosphatase, with the regulatory region of ENO1 changed the expression of PHO5-'lacZ gene to constitutive, irrespective of the concentration of inorganic phosphate in the medium. Furthermore, the GCR1 gene cloned in a multicopy plasmid increased the expression of the ENO1-'lacZ fused genes.

Escherichia coli↗