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Biomedical subjects

A Inaba

Publications and source records attributed to A Inaba.

At least 37 records · Page 2Linked to original sources

Electrophysiological features of central motor conduction in spinocerebellar atrophy type 1, type 2, and Machado-Joseph disease.

OBJECTIVES: To characterise electrophysiologically the central motor conduction of spinocerebellar atrophy type 1 (SCA1), type 2 (SCA2), and Machado-Joseph disease (MJD). METHODS: Motor evoked potentials (MEPs) triggered by transcranial magnetic stimulation (TMS) was used to investigate the functions of corticospinal tracts of 10 patients with SCA1, 10 with MJD, and eight with SCA2 in addition to pathological study of the spinal cord in a patient with SCA1. RESULTS: Central motor conduction time (CMCT) was extremely prolonged and the MEP threshold increased in all patients with SCA1, whereas both were normal in patients with SCA2 or MJD. The MEP size in MJD was larger than normal, but was normal in SCA1 and SCA2. A pathological investigation of the corticospinal tract of the spinal cord of a patient with SCA1 showed selective loss of large diameter fibres. CONCLUSIONS: SCA1, SCA2, and MJD differ in their pathophysiological features of the central motor tract and can be differentiated from each other by MEP values for the lower limb muscles, even though their neurological symptoms are sometimes similar.

Adult↗

X-linked spinal and bulbar muscular atrophy with myasthenic symptoms.

We describe a patient with X-linked spinal and bulbar muscular atrophy (X-SBMA) and myasthenic symptoms. The diagnosis of X-SBMA was established by demonstration of the increased number of CAG repeats in the androgen receptor gene on the X chromosome. This patient was characterized by the clinical symptoms of fatigability, decremental motor responses to repetitive nerve stimulation, and improvement of the myasthenic symptoms with oral administration of pyridostigmine. No serum antibody to acetylcholine receptor was detected. It is suggested that, in the process of chronic denervation and reinnervation of X-SBMA, reinnervated motor endplates may be associated with the defect of neuromuscular transmission.

Genetic Linkage↗

Expression and internal feedback regulation of ACC synthase and ACC oxidase genes in ripening tomato fruit.

We have examined whether or not a positive feedback regulation of gene expression for 1-aminocyclopropane-1-carboxylate (ACC) synthase and ACC oxidase also operates in ripening tomato (Lycopersicon esculentum) fruit during the burst of ethylene production. Two cDNA fragments for ACC synthase and one for ACC oxidase were cloned with high homology to already known genes involved in ethylene biosynthesis in ripening tomato fruit. Accumulation of mRNAs which hybridize to these cDNA probes were induced in mature green fruit within two days by treatment with propylene. In the fruit ripened from the turning stage, red color development, ethylene production, ACC content, and activities of ACC synthase and ACC oxidase increased as maturity progressed. The abundance of two ACC synthase and one ACC oxidase mRNAs in the fruit increased from the turning to pink stage and were followed by a slight decline towards the red stage. These increases in mRNAs abundance with ripening were prevented to a large extent by treatment with the ethylene action inhibitor, 1-methylcyclopropene (MCP). This was most pronounced in the fruit treated with MCP at the turning stage, in which the accumulation of ACC synthase and ACC oxidase transcripts was almost completely eliminated in the first two d, precisely the same stage at which the control fruit had the greatest level of each mRNA accumulation. The inhibition of transcript accumulation recovered to the control level within two to four d. MCP also decreased ethylene biosynthetic activity, although this decrease did not reflect the reduction in the mRNAs accumulation. These results suggest that a strong positive feedback regulation is involved in ethylene biosynthesis at the gene transcriptional level in tomato fruit, even at the stage with a burst of ethylene production.

Alkenes↗

Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 1st communication: absorption, distribution, metabolism and excretion after topical application and subcutaneous administration in rats.

4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antipsoriatic activity. The pharmacokinetic profiles of Am-80 were studied in rats after topical application and subcutaneous administration of 14C-labeled Am-80. After topical application at a dose of 1 g ointment (0.1%)/kg to normal skin rats by the occlusive dressing technique, radioactivity was scarcely detected in the blood or plasma. In the stripped skin rats, plasma radioactivity reached the peak at 2 h and decreased with a half-life of 5.5 h. The recovery of radioactivity in the excreta and carcass amounted to 54.7% of the dose, indicating about six times higher absorption than that in the normal skin rats. After subcutaneous administration at a dose of 1 mg/kg, the maximum concentration of blood radioactivity was attained at 1-2 h and declined with a half-life of 4-5 h until 24 h. Biliary excretion was about 80% of the dose, and enterohepatic circulation was estimated to be 36.5%. Radioactivity was distributed systemically, particularly in abundance in the liver followed by adrenal gland and kidney. Elimination of radioactivity in most tissues was extremely slow and the radioactivity was detected even at 240 h after dosing. There was no gender-related difference in the profile of distribution and elimination of 14C-Am-80 in the rats. Two major metabolic pathways in rats have been postulated for Am-80; one involves the 6- or 7-hydroxylation to yield related hydroxy-Am-80 that lead to the formation of oxo-Am-80, and another involves the hydrolysis of the carboxamide bond to yield tetrahydro-tetramethyl-naphthalenylamine and terephthalic acid. Furthermore, Am-80 itself an 6- or 7-hydroxy-Am-80 were susceptible to the formation of taurine conjugates. In the plasma, unchanged Am-80 was present in a high proportion to total radioactivity, while in the urine and bile the proportion of unchanged Am-80 was low.

Administration, Topical↗

Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 2nd communication: absorption, distribution and excretion after single and consecutive subcutaneous administration in rats.

4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl]benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antisporiatic activity. The accumulation characteristics of Am-80 were examined in rats after a single and consecutive subcutaneous administration of 14C-labeled Am-80 once a day for 24 days, at a daily dose of 0.2 mg/kg. As compared with the single administration, Tmax (1-2 h) and Cmax (about 50 ng eq./ml) of the blood radioactivity were not altered markedly after the consecutive administration. During the daily subcutaneous dosing, the blood level of radioactivity at 24 h after each dosing was also very low. These findings suggested that accumulation in the blood was low after long term consecutive administration of Am-80. The plasma levels of total radioactivity and the proportion of unchanged Am-80 to the total plasma radioactivity, being about 80% at 2 h after administration, and plasma elimination half-life of Am-80, being approximately 3 h, appeared to be hardly affected by the consecutive administration. The cumulative excretion of radioactivity at 168 h after the final dosing was 6.7% and 89.1% in the urine and feces, respectively. The radioactivity remaining in the carcass at this time was about 3% of the total dose. The excretion profile was not altered by the consecutive administration. In most tissues, the concentration of radioactivity at 24 h after each dose reached a steady-state within 24 doses. At 2 h after the consecutive administration for 24 days, the highest concentration of radioactivity was found in the liver followed by the adrenal gland. Accumulation and delayed elimination of radioactivity in most tissues, especially in the adrenal gland, fat, skin and epididymis, were evidently observed as predicted from the previous study where 14C-Am-80 was administered at a dose of 1 mg/kg. The profile of accumulation and retention of radioactivity after the consecutive administration may be considered as a common characteristic of retinoids, such as etretinate.

Animals↗

Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl]benzoic acid. 3rd communication: placental transfer and excretion into milk in rats.

4-[5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl]benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antipsoriatic activity. Placental transfer and excretion into milk after administration of 14C-Am-80 to pregnant or nursing rats were investigated in view of reproductive and developmental toxicity studies. When 14C-Am-80 was administered topically at a dose of 10 mg/kg to normal-skin pregnant rats on the 12th day of pregnancy, plasma radioactivity in the dam and fetus was detected only at low levels. However, at a dose of 1 mg/kg to the stripped-skin pregnant rats, radioactivity levels peaked at 6 h in the maternal plasma (188.7 ng eq./g) and fetus (64.6 ng eq./g) and at a dose of 10 mg/kg, the peak maternal plasma level of radioactivity and the concentration of radioactivity in the fetus up to 24 h after dosing rose about 10-fold in proportion to the increased dose. At both doses, the radioactivity level in the fetus at the peak corresponded to approximately one-third of the maternal plasma level. When 14C-Am-80 was administered subcutaneously at a dose of 1 mg/kg to pregnant rats on the 12th day of pregnancy, radioactivity in the fetus peaked at 4 h after dosing, being about one-fourth of the maternal plasma level at the same time point. Radioactivity in the fetus after subcutaneous administration of 14C-Am-80 at a dose of 1 mg/kg to pregnant rats on the 19th day of pregnancy peaked (156.4 ng eq./g) at 4 h after dosing, corresponding to approximately one-half the maternal plasma level at the same time point, and then decreased gradually. Among the fetal tissues, relatively high radioactivity was found in the liver. Whole-body autoradiography showed that in most tissues in the dam, the distribution pattern of radioactivity was similar to that in the non-pregnant rat. The concentration of radioactivity in the milk after subcutaneous administration of 14C-Am-80 at a dose of 1 mg/kg to lactating rats on the 9th day after delivery peaked at 8 h after dosing, being 94 times greater than that in the plasma. Unchanged Am-80 in the milk was largely recovered after hydrolysis of hexane extracts of the intact milk with lipase, suggesting extensive incorporation of Am-80 into the triglyceride in the milk because of its benzoic acid structure and high lipophilicity. As for radioactive metabolites which have hitherto been identified in rats, only M-6 (taurine conjugate of Am-80) and tetrahydro-tetra-methyl-naphthylamine (TTNA) were detectable in small amounts in the milk.

Administration, Topical↗

Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 4th communication: absorption, metabolism, excretion and plasma protein binding in various animals and man.

4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl]benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antipsoriatic activity. Pharmaco-kinetic profiles of Am-80 were studied in dogs, mice and rabbits after percutaneous or subcutaneous administration of 14C-Am-80. Plasma protein binding of 14C-Am-80 was also studied in rats, dogs and humans. After topical application of 14C-labeled Am-80 by occlusive dressing technique at a dose of 1 mg 14C-Am-80/1,000 mg ointment/kg, the blood and plasma levels of radioactivity were below the detection limit in normal-skin dogs. In normal skin mice and rabbits, the plasma radioactivity peaked at 8 h (40.8 ng eq./ml) and at 12 h (34.0 ng eq./ml) after application, respectively. Percutaneous absorption of 14C-Am-80 was less than 2% of the dose for dogs, 34% for mice and 23% for rabbits. After subcutaneous administration at a dose of 1 mg/kg to mice, dogs and rabbits, plasma levels of radioactivity peaked at 1, 4 and 4 h after dosing with a concentration of 614.0, 902.9 and 757.7 ng eq./ml and then it declined with half-lives of 2.4, 7.2 and 4.1 h, respectively. Urinary and fecal excretion of radioactivity after subcutaneous administration at a dose of 1 mg/kg was 3.5 and 94.7% of the dose in dogs, 27.0 and 73.2% in mice and 43.5 and 45.6% in rabbits. A possible gastrointestinal secretion, which might lead to excretion into feces, was suggested from the results with bile-duct-cannulated dogs. Unchanged Am-80 was present in high amounts in the plasma and bile or feces of all animal species tested except in rat bile, in which Am-80 was predominantly detected in the form of its taurine conjugate (M-6). Hydroxylation of Am-80 to yield 7-hydroxy-Am-80 (M-4) and 6-hydroxy-Am-80 (M-3), which lead to the formation of 6-oxo-Am-80 (M-5), were commonly observed in all animal species. Taurine conjugation reaction of unchanged Am-80 and hydroxy-Am-80 (to form M-6 and both M-1 and M-2, respectively) was distinct in rats and dogs, but, hardly detected in mice and rabbits. The presence of tetrahydro-tetramethyl-naphtylamine (TTNA) was most marked in mice, followed by rabbits and rats, but it was almost absent in dogs. HPLC-RIA analysis of human samples obtained from the phase II and phase III clinical trials of Am-80 ointment suggested that fecal excretion was the major elimination route, and that hydroxylation and taurine conjugation reaction of unchanged and hydroxy-Am-80 also occurred. Unchanged Am-80 was predominant in human plasma as compared with metabolites M-1 to M-6. In vitro binding of 14C-Am-80 to the plasma protein was found to be more than 99% in rats, dogs and humans. In vivo plasma protein binding of 14C-Am-80 and/or its radioactive metabolites was also found to be more than 98% in rats and dogs after subcutaneous administration of 14C-Am-80. In both dogs and humans, in vitro. 14C-Am-80 appeared to be bound predominantly to serum albumin. The binding of 14C-Am-80 to human serum albumin was scarcely affected in the presence of diazepam, digitoxin or warfarin, indicating that there are no specific binding sites for Am-80 on serum albumin.

Administration, Topical↗

Proximal and segmental motor nerve conduction in the sciatic nerve produced by percutaneous high voltage electrical stimulation.

Percutaneous high voltage electrical stimulation was applied to the proximal sciatic nerve at the hip in 18 normal subjects to evaluate motor conduction in the proximal sciatic nerve, and short-segment stimulation of the sciatic and posterior tibial nerves was given in 6 normal subjects. Compound muscle action potentials (CMAPs) were recorded from the abductor hallucis (AH) and extensor digitorum brevis (EDB) muscles. Supramaximal stimulation was easily obtained at the proximal sciatic nerve and all the sites in the short-segment stimulation. The motor nerve conduction velocity of the sciatic nerve between the hip and the popliteal fossa was 49.2 +/- 4.24 m/sec in the tibial division and 54.1 +/- 6.48 m/sec in the peroneal division. The respective peak-to-peak amplitude and negative-peak areas of the CMAPs at the hip were reduced to 86.8 +/- 5.65% and 97.3 +/- 5.36% for the tibial division, and 93.4 +/- 7.06% and 96.8 +/- 5.09% for the peroneal division as compared to the values for the popliteal fossa. The negative-peak duration of the CMAPs at the hip point were increased to 109.2 +/- 7.2% for the tibial nerve and 107.1 +/- 5.68% for the peroneal nerve as compared with the duration at the popliteal fossa. This method is non-invasive and useful for evaluating motor nerve conduction in the lower limb.

Adult↗

Pure progressive clumsiness due to parietal atrophy in a young adult.

Progressive clumsiness developed in the right hand of a 33-year-old man, became bilateral and evolved very slowly for ten years. Another neurological deficit was restricted to a slight impairment of superficial sensations. Magnetic resonance imaging verified an atrophy of bilateral parietal lobes. The cerebral blood flow was markedly decreased in the atrophic area. Pure clumsiness of a very slowly progressive course due to parietal atrophy has never been reported in such a young adult. This clinical picture may suggest another variety of degenerative process.

Adult↗

The F wave disappears due to impaired excitability of motor neurons or proximal axons in inflammatory demyelinating neuropathies.

OBJECTIVES: Investigation of pathophysiology of F wave disappearance in demyelinating neuropathies. METHODS: The peripheral motor nerve conduction was studied by motor evoked potential (MEP) on transcranial magnetic stimulation as well as conventional nerve conduction studies before and after the treatment in 26 patients with inflammatory demyelinating neuropathies. In addition, serum antiganglioside antibodies in the acute or active stage were examined. RESULTS: The F wave was abolished in 10 patients. Seven of the 10 patients showed motor evoked potentials (MEPs) on transcranial magnetic stimulation that ranged from 1-4 mV. In six of them the F wave reappeared in the recovery stage, but the MEP size did not change. This may be caused by humoral factors, because the F wave reappeared immediately after plasma exchange or intravenous immunoglobulin treatment. A correlation of F wave disappearance with the presence of serum antiganglioside antibodies was found. CONCLUSIONS: The major pathophysiology of F wave disappearance in demyelinating neuropathies is impairment of motor neuron excitability or prolonged refractoriness of the most proximal axon for backfiring. The conventional interpretation that absent F waves suggest a conduction block at the proximal site is often inadequate.

Acute Disease↗

Double cortical stimulation in amyotrophic lateral sclerosis.

OBJECTIVE: Transcranial double magnetic stimulation on the motor cortex was used to investigate central motor tract function in 16 patients with amyotrophic lateral sclerosis, five with spinal muscular atrophy, and 16 age matched normal controls. METHODS: Surface EMG responses were recorded from the relaxed abductor pollicis brevis (APB) muscle. RESULTS: Responses to test stimuli were markedly attenuated by a subthreshold conditioning stimulus given at a condition-test (C-T) interval of 1-4 ms in normal controls and patients with spinal muscular atrophy, but attenuation was mild in patients with amyotrophic lateral sclerosis. In the normal controls this suppression was caused by activation of the intracortical inhibitory mechanism because responses to electrical test stimuli and the H wave were not suppressed by the same magnetic subthreshold conditioning stimulus. In amyotrophic lateral sclerosis the effect of the conditioning cortical stimulus on the H wave was also in the normal range. CONCLUSION: The intracortical inhibitory mechanism may be impaired in patients with amyotrophic lateral sclerosis.

Aged↗

Focal conduction block in compression neuropathy of the proximal sciatic nerve.

Direct percutaneous stimulation of the proximal sciatic nerve with a high voltage electrical stimulator was given to a patient with acute sciatic compression neuropathy. Results clearly showed a focal conduction block at the sciatic notch, which could not be precisely localised and quantified by conventional electrodiagnostic methods.

Action Potentials↗

Neighborhood Women's Health Watch: partners in community care.

A successful program for delivering prenatal care in rural Hawaii incorporated women volunteers from the local community known as the "Neighborhood Women's Health Watch" (NWHW). Knowledgeable about the cultural mores among the various Asian American and Pacific Islander ethnic groups within the community, these respected women established strong collegial relationships with a public health nursing team to assist in various monitoring and care activities designed for pregnant and postpartum women. This article will address recruitment, training, and role functions of the NWHW, including recommendations for the development of similar programs.

Community Health Nursing↗

Paraneoplastic encephalo-myelo-ganglionitis: cellular binding sites of the antineuronal antibody.

The cellular binding sites of an antineuronal antibody were characterized in an autopsy case of the paraneoplastic encephalo-myelo-ganglionitis. A 61 year-old woman developed a subacute sensorimotor polyneuropathy and, later, multiple involvement of cranial nerves, disturbance of consciousness, and generalized seizure. An autopsy revealed a small cell lung carcinoma and neuropathological changes that included disseminated encephalitis, spinal anterior horn lesions, severe loss of dorsal root ganglion neurons, and secondary degeneration and loss of the nerve fibers in the spinal posterior column and peripheral nerves. The serum IgG from the patient contained antineuronal antibody(s) including an antibody to 35- to 37-kDa neuronal antigens called anti-Hu as demonstrated in Western blot. In immunohistochemical studies, the serum IgG immunostained neurons of the brains, spinal cords, and dorsal root ganglia of humans or rats. Confocal laser-scanning microscopy revealed binding of the patient's IgG in the neuronal nuclei and cytoplasm, but not in the nucleoli. In immunoelectron microscopic studies, immunolabelling with the IgG was found diffusely in the karyoplasm, excluding nucleoli, and in the cytoplasmic matrix between the cisternae of the reticulums, Golgi apparatus, and mitochondria. Encephalo-myeloganglionitis is a clinicopathological entity frequently associated with the presence of neoplasm and antineuronal antibody, however, the role of the antibody in the pathogenesis remains to be elucidated.

Autoantibodies↗

Prostaglandin E2 levels and lymphocyte subsets in portal venous drainage of colorectal cancers.

Local immunosurveillance may play an important role in the growth and spread of tumors. To investigate the local immune response, we determined prostaglandin E2 (PGE2) levels (n = 23) and lymphocyte subsets (n = 10) in the portal vein draining the tumors of patients with colorectal cancer. PGE2 levels in the portal vein were significantly higher than those in the radial artery. Portal PGE2 levels in patients with advanced stage tumors (Duke's C and D) and lymph node metastases were significantly higher than those of patients with Duke's A and B tumors without lymph node metastases. Moreover, four of the nine patients with portal PGE2 levels greater than 100 pg/mL had liver metastases within 2 years of surgery. There were no differences in lymphocyte subsets between the portal vein and the radial artery. PGE2 levels in the portal vein draining colorectal tumor may thus be closely related to tumor progression and recurrence and may serve as a predictor of tumor recurrence in patients with colorectal cancer.

Adult↗

Analysis of mitochondrial DNA in two species of the bipectinata species complex of Drosophila.

Drosophila bipectinata and D. malerkotliana are members of the bipectinata species complex of the ananassae subgroup in the melanogaster species group of Drosophila. The mtDNA from 18 isofemale strains of these species was analyzed, using 13 restriction endonucleases. Altogether, eight mtDNA haplotypes were detected, of which the haplotype 1B was shared by the two species. Restriction cleavage map of mtDNA of these species was constructed. The net nucleotide substitutions per site calculated between these species was found to be 0.0002. This value appeared to be relatively much lower than expected at the interspecific level, even lower than that reported between two subspecies of Drosophila despite both being good species. This extreme closeness of their mtDNAs is discussed in the light of recent findings.

Animals↗

Induction by Electric Currents of Ethylene Biosynthesis in Cucumber (Cucumis sativus L.) Fruit.

The effects of an electric current on ethylene biosynthesis were investigated in cucumber (Cucumis sativus L.) fruit that were producing almost no ethylene. Direct currents at 0.5 to 3.0 milliamperes induced much ethylene synthesis, with a rapid continuous increase in the rate, which reached a peak within 5 to 6 hours and then decreased. The rate of production was greater with a stronger current. Ethylene production was not observed after the use of a sine-wave alternating current (60 hertz) at 3 milliamperes, the magnitude at which a direct current had the greatest effect. The activity of 1-aminocyclopropane-1-carboxylic acid (ACC) synthase and ethylene forming enzyme (EFE) increased before the rise in ethylene production. ACC synthase and EFE were activated sixfold and fourfold, respectively, by 2 hours. The concentration of ACC increased linearly up to 6 hours and then decreased. Ethylene induction by an electric current was suppressed almost completely by the infiltration of the cucumbers with 5 millimolar aminooxyacetic acid, an inhibitor of ACC synthase, and was also suppressed 70% by 5 millimolar salicylic acid, an inhibitor of EFE. The results indicate that the ethylene induced by the direct current was synthesized via the ACC-ethylene pathway as a result of electrical stress, a new kind of stress to be identified.

Journal Article↗