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Biomedical subjects

M Machida

Publications and source records attributed to M Machida.

At least 127 records · Page 7Linked to original sources

[Therapy of renal cell carcinoma. 3. Interferon therapy].

Human lymphoblastoid interferon (HLBI-alpha) or recombinant human leukocyte interferon (HLIF-alpha) was administered to ten patients suffering from renal cell carcinoma at a daily dose of 5 X 10(6) units. The efficacy of interferon was assessed in nine patients who had received HLBI-alpha or HLIF-alpha for more than eight weeks. One patient (11%) demonstrated complete response (CR), three patients (33%) showed no change and five patients (56%) continued to have progressive disease. CR was obtained after 30 weeks under HLBI-alpha and FT-207 combination therapy. The main side effects were fever, anorexia, general fatigue and hematologic toxicities. Cessation of interferon therapy due to side effects was necessary in three patients. In conclusion interferon is one of the most valuable agents in the treatment of renal cell carcinoma.

Adult↗

Nucleotide sequence and characteristics of the gene for L-lactate dehydrogenase of Thermus caldophilus GK24 and the deduced amino-acid sequence of the enzyme.

The gene for L-lactate dehydrogenase (LDH) (EC 1.1.1.27) of Thermus caldophilus GK24 was cloned in Escherichia coli using synthetic oligonucleotides as hybridization probes. The nucleotide sequence of the cloned DNA was determined. The primary structure of the LDH was deduced from the nucleotide sequence. The deduced amino acid sequence agreed with the NH2-terminal and COOH-terminal sequences previously reported and the determined amino acid sequences of the peptides obtained from trypsin-digested T. caldophilus LDH. The LDH comprised 310 amino acid residues and its molecular mass was determined to be 32,808. On alignment of the whole amino acid sequences, the T. caldophilus LDH showed about 40% identity with the Bacillus stearothermophilus, Lactobacillus casei and dogfish muscle LDHs. The T. caldophilus LDH gene was expressed with the E. coli lac promoter in E. coli, which resulted in the production of the thermophilic LDH. The gene for the T. caldophilus LDH showed more than 40% identity with those for the human and mouse muscle LDHs on alignment of the whole nucleotide sequences. The G + C content of the coding region for the T. caldophilus LDH was 74.1%, which was higher than that of the chromosomal DNA (67.2%). The G + C contents in the first, second and third positions of the codons used were 77.7%, 48.1% and 95.5% respectively. The high G + C content in the third base caused extremely non-random codon usage in the LDH gene. About half (48.7%) the codons in the LDH gene started with G, and hence there were relatively high contents of Val, Ala, Glu and Gly in the LDH. The contents of Pro, Arg, Ala and Gly, which have high G + C contents in their codons, were also high. Rare codons with U or A as the third base were sometimes used to avoid the TCGA sequence, the recognition site for the restriction endonuclease, TaqI. Two TCGA sequences were found only in the sequence of CTCGAG (XhoI site) in the sequenced region of the T. caldophilus DNA. There were three segments with similar sequences in the two 5' non-coding regions, probably the promoter and ribosome-binding regions, of the genes for the T. caldophilus LDH and the Thermus thermophilus 3-isopropylmalate dehydrogenase.

Amino Acid Sequence↗

What determines the latency and amplitude of stationary peaks in far-field recordings?

In 20 radial nerves from 10 healthy persons, a referential derivation from the tip of the first or second digit registered two biphasic stationary peaks, PI-NI and PII-NII, following stimulation of the nerve in the forearm. These two peaks occurred slightly before the arrival of the propagating impulse at the wrist and at the base of the digit, respectively. With stepwise reduction of stimulation from a maximal to a threshold intensity, the far-field potential decreased in amplitude linearly with the near-field potential recorded at the junction of the volume conductor. Abduction of the first digit or flexion of the second and third digits altered the waveform and, to a lesser degree, the latency of the far-field peaks. However, these changes appeared in an inconsistent manner, which we were unable to characterize. We conclude that in far-field recording a stationary peak results at the border of the adjoining volume conductors in proportion to the magnitude of the propagating axonal volley approaching the boundary.

Adult↗

New approach for diagnosis in herniated lumbosacral disc. Dermatomal somatosensory evoked potentials (DSSEPs).

Dermatomally activated somatosensory evoked potentials (DSSEPs) were recorded over the scalp of 50 healthy subjects and 40 patients who later underwent exploration for herniated lumbosacral disc. DSSEPs normally consisted of three negative peaks, N40, N56, and N78, and N41, N59, and N82 after bilateral stimulation of L5 and S1 dermatomes, respectively. In the patient group, the first two peaks were often abnormal in the presence of a clinical sensory deficit, whereas the third peak tended to remain normal. At surgery, herniated disc was confirmed in all but six patients. The findings in the myelogram were misleading in eight patients, showing either false-positive or false-negative results. The DSSEPs were normal in six patients with documented disc protrusion at the level of the L5 or S1 root. The test was also normal in another case with herniation at the level of the S2 root. In this series, DSSEPs accurately predicted the level and degree of lumbosacral root involvement. In addition to myelography and other electrodiagnostic tests, the DSSEPs are valuable non-invasive diagnostic tool for the evaluation of herniated lumbosacral disc.

Adolescent↗

Pharmacokinetics of a new quinolone, AM-833, in mice, rats, rabbits, dogs, and monkeys.

The pharmacokinetics of AM-833 [6,8-difluoro-1-(2-fluoroethyl)-1, 4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid] were studied in mice, rats, rabbits, dogs, and monkeys by reversed-phase high-performance liquid chromatography. AM-833 was rapidly and completely absorbed from the digestive tracts of mice, rats, and dogs. About half of AM-833 bound to rat and dog serum proteins. Drug levels in lung, spleen, liver, and kidney tissues of rats and dogs were greater than the respective levels in serum but lower in brain tissue. Drug levels in tissues declined with the decrease in levels in serum. AM-833 penetrated rapidly and well into inflammatory exudate of rats. Elimination half-lives in serum were species dependent, ranging from 1.57 h in rabbits to 9.42 h in dogs. Profiles of drug levels in serum were dose related over a single dose range from 2 to 40 mg/kg and not modified significantly during multiple dosing in dogs. Unchanged AM-833 was excreted in urine and bile in both rats and dogs. The metabolism of AM-833 was suggested by evidence that 24-h total recovery of unchanged AM-833 in urine and bile accounted for about half of the intravenous dose in rats.

Animals↗

Relation between size of compound sensory or muscle action potentials, and length of nerve segment.

In 24 median nerves from 12 healthy subjects, antidromic digital sensory potentials progressively diminished in size, averaging 40.4, 37.0, 30.7, and 23.9 microV X msec with stimulation at the palm, wrist, elbow, and axilla, respectively. In contrast, compound muscle action potentials changed minimally, measuring 19.4, 19.8, 19.0, and 18.2 mV X msec, respectively. Similar studies of the ulnar and radial nerves showed identical trends. Physiologic temporal dispersion can mimic conduction block of sensory nerves by summating the peaks of opposite polarity generated by fast- and slow-conducting axons. This type of cancellation affects muscle responses much less because motor unit potentials of longer duration superimpose nearly in phase, given the same latency shift as the sensory potentials.

Action Potentials↗

[Effects of cisapride on lower esophageal sphincter pressure and gastroduodenal motor activity in man].

Manometric study was performed to investigate the effects of cisapride, a new non-antidopaminergic gastrointestinal prokinetic compound, on interdigestive lower esophageal sphincter pressure (LESP) and gastroduodenal motility using infused catheter technique. The subjects consisted of 9 healthy volunteers and 29 patients with progressive systemic sclerosis (19), reflux esophagitis (8) and others (2). 4 mg of cisapride was given by bolus injection, continuous infusion or oral administration. The following results were obtained: Intravenous and oral cisapride increased LESP compared with basal pressure. Especially, bolus injection of cisapride caused a significant elevation of LESP during 30 minutes after administration. After administration of cisapride, gastroduodenal motility was accelerated gradually, then inducing IMC-like contractions. By bolus injection, IMC-like contractions were induced in healthy subjects more frequently than in patients group. On the other hand, motility index of stomach and duodenum showed persistent increase in patients group compared with healthy subjects. Cisapride-induced IMC-like contractions initiated from LES and upper part of stomach and mediated to duodenum, though aborad migration was not confirmed in the present study.

Adolescent↗

Effects of dietary methionine, cystine, and glycine on endogenous hypercholesterolemia in hepatoma-bearing rats.

The effects on hypercholesterolemia of dietary additions of cystine (Cys), methionine (Met), glycine (Gly), and a combination of Met and Gly to a 20% casein diet were studied in male Donryu rats subcutaneously implanted with an ascites hepatoma line of AH109A cells. The hepatoma-bearing rats fed the 20% casein diet lapsed into both endogenous hypertriglyceridemia and hypercholesterolemia when compared to hepatoma-free (normal) rats fed the same diet. The hypercholesterolemia was due to an elevation (3.2 fold) in the very low-density lipoprotein plus low-density lipoprotein (VLDL + LDL)-cholesterol (Ch) level. The high-density lipoprotein (HDL)-Ch level was slightly but significantly decreased. These lipoprotein changes in hepatoma-bearing rats resulted in a marked (4.5 fold) increase in the atherogenic index (AI, (VLDL + LDL)-Ch/HDL-Ch) in comparison with that of tumor-free rats. The dietary additions of 1.2% Met, 1.2% Cys, and a combination of 1.2% Met and 2.5% Gly significantly suppressed the hepatoma-induced increase in (VLDL + LDL)-Ch with no influence on the hepatoma-induced decrease in HDL-Ch, leading to a noticeable fall in AI. These results indicate that hepatoma-bearing rats are useful as an endogenously hyperlipidemic model and that some dietary amino acids are capable of improving hepatoma-induced hypercholesterolemia and abnormal serum lipoprotein profiles.

Animals↗

[Case report of choriocarcinoma of testicular origin indicating marked efficacy of a combination chemotherapy of methotrexate, vincristine, actinomycin D, cyclophosphamide, adriamycin and melphalan].

The patient was a 26-year-old male. He was admitted to our hospital with a chief complaint of hemoptysis, cough and left scrotal mass on May 9,1984. Chest X-ray film, LAG and CT revealed multiple lung, lymph node and cerebral metastases. Based on a diagnosis of testicular neoplasm, orchiectomy was performed on May 14,1984. PVB chemotherapy (Cis-diamminedichloro-platinum, Vinblastine and Pepleomycin) was administered. Because he got worse, however, he was treated with another combination chemotherapy, consisting of Methotrexate (MTX, 100 mg/m2 intravenous push (i.v.), 200 mg/m2 12-h infusion, day 1. The dose of MTX was increased with each course. Maximum dose of MTX was 900 mg/m2/day), Vincristine (1.0 mg/m2 i.v. day 1.) Actinomycin D (10 micrograms/kg i.v. days 3.4.5), Cyclophosphamide (600 mg/m2 i.v. day 3.), Adriamycin (30 mg/m2 i.v. day 8.) and Melphalan (6 mg/m2 p.o. day 8.). After 6 courses of this regimen, distant metastases disappeared or were reduced to under one tenth, and complete remission was obtained without severe side effects. The patient was in good health on March 30, 1985.

Adult↗

Allosteric effect of fructose 1,6-bisphosphate on the conformation of NAD+ as bound to L-lactate dehydrogenase from Thermus caldophilus GK24.

The allosteric effect of fructose 1,6-bisphosphate (Fru-1,6-P2) on L-lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) from Thermus caldophilus GK24 was studied by means of 1H NMR analyses. The conformation of NAD+ as bound to the T. caldophilus enzyme was elucidated by analyses of the transferred nuclear Overhauser effects (TRNOE), in the presence and the absence of the allosteric effector, Fru-1,6-P2. Upon binding of Fru-1,6-P2 to the enzyme, the ribose ring of the adenosine moiety of NAD+ is converted from the C2'-endo form to the C3'-endo form. This C3'-endo form of the adenosine moiety is similar to that of NAD+ as bound to nonallosteric vertebrate enzymes. However, the anti conformation of the adenine-ribose bond of NAD+ as bound to the T. caldophilus enzyme is not affected by the binding of Fru-1,6-P2. In contrast, the syn conformation of the nicotinamide-ribose bond is converted to the anti form on the binding of Fru-1,6-P2, while the ribose ring remains in the C3'-endo form as found in the case of a nonallosteric enzyme. Such a conformational change of enzyme-bound NAD+ as found on TRNOE analysis is essentially involved in the allosteric regulation of the T. caldophilus enzyme by Fru-1,6-P2.

Adenosine↗

Stationary negative potentials near the source vs. positive far-field potentials at a distance.

We studied the field distribution of referentially recorded negative potentials after stimulation of the median nerve at the wrist in 15 normal subjects. When recorded from multiple sites along the lateral aspect of the arm with the reference electrode at the knee, 3 negative peaks, N3, N6 and N9, appeared at fixed latencies. Of these N3 and N6 were highest in amplitude at the distal insertion of the brachioradialis and the distal end of the deltoid, respectively, and N9, at the acromion. With stimulation of the finger, the negative peaks shifted in latency by about 3 msec, indicating an anatomically fixed generator source for each component. When compared to far-field potentials, N9 was of the same latency as scalp recorded P9, that extended to the arm contralateral to the side of stimulation and to the upper half of the trunk. In contrast, N6 extended to the scalp with P6 spreading to the lower half of the body. When two subjects were connected by the arm, stationary negative or positive peaks were transmissible from the stimulated to the non-stimulated subject. When the stimulated arm of the first subject was in contact with the second subject, N3, N6 and N9 were recorded in the latter. Only P9 was registered when the unstimulated arm was in contact with the second subject. We conclude that N3, N6 and N9 are stationary negative potentials generated at certain points along the nerve pathway, probably representing a negative counterfield for positive far-field peaks, P3, P6 and P9. These stationary potentials can spread widely in a volume conductor and can even be detected in a non-stimulated subject making a close contact to the generator source.

Adolescent↗

Fructose 1,6-bisphosphate-dependent L-lactate dehydrogenase from Thermus aquaticus YT-1, an extreme thermophile: activation by citrate and modification reagents and comparison with Thermus caldophilus GK24 L-lactate dehydrogenase.

Heat-stable fructose 1,6-bisphosphate-dependent L-lactate dehydrogenase [EC 1.1.1.27] was purified from an extremely thermophilic bacterium, Thermus aquaticus YT-1. The amino acid composition and NH2-terminal 34 amino acid sequence of the enzyme were determined. Its NH2-terminal sequence shows high homology with those of Thermus caldophilus GK24 (82% identity) and some other bacterial L-lactate dehydrogenases (44-53% identity), indicating the close phylogenic relationship of the two Thermus species. At the same time, the two Thermus L-lactate dehydrogenases were found not to be identical not only chemically but also kinetically and immunologically. Citrate activated the T. aquaticus enzyme in the weak acidic pH region, while fructose 1,6-bisphosphate did in both acidic and neutral pH regions. The maximum activity obtained with citrate at pH 5.0 was about 2.5 times higher than that in the presence of fructose 1,6-bisphosphate at pH 6.7. The enzymes modified with 2,3-butanedione, acetic anhydride and diethyl pyrocarbonate in the presence of both NADH and oxamate were desensitized to fructose 1,6-bisphosphate, and the modified enzymes were active even in the absence of fructose 1,6-bisphosphate. All of the modified enzymes examined were still activated by citrate similarly to the native enzyme. These results suggest that the mechanism of activation by citrate is different from that by fructose 1,6-bisphosphate, and that the citrate-binding site is different from the fructose 1,6-bisphosphate-binding site.

Amino Acids↗