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K Mokuno

Publications and source records attributed to K Mokuno.

At least 37 records · Page 2Linked to original sources
PubMed1992

Structure and expression of proteolipid protein in the peripheral nervous system.

Proteolipid protein (PLP), the major myelin protein in the central nervous system (CNS), is also made by Schwann cells (SC) in the peripheral nervous system (PNS) but is not incorporated into the SC myelin sheath. We analyzed several PLP cDNA clones isolated from a rat sciatic nerve cDNA library and found that their coding sequences were identical to PLP cDNAs previously isolated from the CNS. In addition, we have discovered an unusual form of PLP message, present in both brain and sciatic nerve RNA, that is likely formed by alternative splicing within the 3' untranslated region of the primary PLP transcript. The absence of PLP from the SC myelin sheath thus cannot be explained by an alteration in its amino acid sequence. Steady-state levels of PLP mRNA in SC cultures treated with the cAMP analogue dibutyryl cAMP (dBcAMP) were not increased, whereas dBcAMP increased steady-state levels of mRNA encoding the major myelin protein, P0. We have also shown that expression of PLP, unlike that of P0, is regulated in SC in vitro at a posttranscriptional level. Finally, the steady-state levels of P0 mRNA are much more dramatically reduced than those of PLP mRNA during Wallerian degeneration of the peripheral nerve. Thus PLP expression in the PNS is probably controlled by different molecular mechanisms from P0, and may not be part of the coordinate program of myelin gene expression. In contrast to its expression in the PNS, transcription of PLP in the CNS is coordinately regulated along with the other myelin protein genes, suggesting there may be differences in the cis-acting elements and transacting factors involved in the regulation of PLP transcription in SC and oligodendrocytes (OC). Consistent with this notion, we have found that most PLP transcripts are initiated at the more proximal of two start sites in the PNS, while in the CNS proportionally more PLP transcripts are initiated from the distal start site. We propose that the proximal site, utilized predominantly in SC, is responsible for maintenance expression of PLP and is not inducible, while the distal site is responsible for the rapid, inducible increase of PLP message during brain development.

Animals↗
PubMed1992

The mechanism of perturbation in monoamine metabolism by L-dopa therapy: in vivo and in vitro studies.

In the cerebrospinal fluid of the patients with Parkinson's disease treated with L-DOPA, L-3-O-methyldopa was the major metabolite of administered L-DOPA. Using a dopaminergic cell model, clonal rat phenochromocytoma PC 12h cells, and by microdialysis of the rat striatum it was proved that L-3-O-methyldopa was taken up into monoamine neurons by transport system specific for aromatic L-amino acids and inhibited transport of L-DOPA and other amino acids competitively. L-3-O-Methyldopa depleted allosteric regulation of the biopterin cofactor on activity of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis. Depletion of the allostery may perturb the buffer action of endogenous L-DOPA synthesis that stabilizes dopamine level in the brain. By these mechanisms L-3-O-methyldopa may reduce clinical effectiveness of administered L-DOPA and be involved in wearing-off phenomenon. L-DOPA inhibited the activity of tryptophan hydroxylase and thus serotonin synthesis, which may be related to psychiatric side-effects in the patients under L-DOPA therapy.

Aged↗
PubMed1992

[Neuron-specific enolase (NSE) and S-100b protein in cerebrospinal fluid of patients with cervical spondylosis--the relations with MRI findings and the changes of NSE and S-100b protein levels through Glisson's traction].

We have previously reported that NSE and S-100b protein (S-100) could be used as reliable markers to evaluate the damage of the spinal cord in cervical spondylosis (CS) and ossification of posterior longitudinal ligament (OPLL). In the present study we made MRI in 21 patients with CS. There was a positive correlation between the NSE level in CSF and the degree of the spinal cord compression shown by MRI. In 10 cases of CS we examined these specific protein levels in CSF before and after the Glisson's traction therapy for one month. In seven of them the NSE levels decreased with the clinical improvements. On the other hand, 2 cases showed the rise of NSE levels after the traction. One of them became clinically worse during the therapy, while in another case the NSE levels changed within the normal range. The level of NSE in the other case was unchanged. In 57-year-old patient with CS myelopathy we examined the NSE levels chronologically. The NSE level changed in parallel with his clinical features. We suggest that NSE level in CSF may be a useful marker to estimate the change of the degree of the spinal cord damage in CS.

Female↗
PubMed1992

[Cerebrospinal fluid levels of 28 kDa calcium-binding protein in patients with neurological diseases].

Vitamin D-dependent calcium-binding protein (Calbindin-D: CaBP) (MW 28 kDa) is present in high concentrations in the central nervous system (CNS), especially in the cerebellum. In the cerebellum, CaBP is localized in Purkinje cells. By using an enzyme immunoassay method, we measured the cerebrospinal fluid (CSF) levels of CaBP in 96 neurological patients and 24 control subjects, and evaluated the clinical usefulness of determining CaBP, especially in the diagnosis of cerebellar damage. CSF CaBP levels were strikingly elevated in patients with cerebellar lesions, including primary spinocerebellar degeneration (SCD), subacute cerebellar degeneration with lung cancer, Wernicke-Korsakoff syndrome, as well as in patients with cerebrovascular disease (CVD) without involvement of the cerebellum. In these 2 groups, neuron-specific enolase (NSE) levels were determined. The ratio of CaBP to NSE (CaBP/NSE) in patients with cerebellar lesions was higher than that in CVD, reflecting differences in lesions between these 2 groups. In the SCD group, multiple system atrophy (MSA) showed higher CaBP levels than the other types of SCD. Probably it reflects remarkable damage of the Purkinje cells in MSA. In MSA, the CaBP levels decreased with the duration of illness. In myelopathy, neuropathy, meningitis, multiple sclerosis, and other degenerative diseases, the increase of CaBP was not remarkable. Our results suggested that CSF CaBP is considered to be a marker of cerebellar damage.

Adolescent↗
PubMed1992

[Central nervous system disorders in myotonic dystrophy--with special reference to neuron-specific enolase, S-100b protein and creatine kinase BB isoenzyme levels in CSF].

In order to evaluate central nervous system disorders in myotonic dystrophy (MyD), neuron-specific enolase (NSE), S-100b protein and creatine kinase BB (CK-BB) isoenzyme were measured using enzyme immunoassay in MyD. Intelligence quotient (IQ) test (WAIS, 17 cases), electro-encephalography (17 cases) and brain computed tomography (18 cases) were examined. In patients with MyD, NSE level was significantly elevated in comparison with 25 age-sex matched control subjects. In some cases of MyD levels of S-100b protein and CK-BB in CSF were elevated. IQ test disclosed intellectual impairment in 70.6% of the patients examined and EEG study demonstrated slowing of basic rhythm in the majority of the cases. On brain CT both enlarged ventricles and dilated sulci were commonly found. The results of the present study suggest that in MyD the CNS is involved not only functionally but structurally as well. Since NSE, S-100b and CK-BB are localized in neuronal and glia cells, their elevated levels in CSF indicate existence of organic lesions in the central nervous tissue in patients with MyD.

Adult↗
PubMed1992

[Cerebrospinal fluid neuron-specific enolase (NSE) and S-100b protein in Guillain-Barré syndrome--their relations to prognosis].

We measured the cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) using enzyme immunoassay methods in 12 patients with Guillain-Barré syndrome (GBS), and 46 control subjects, and evaluated their clinical values in relation to prognosis. The 4 patients with the remarkably elevated level of NSE or S-100b in the acute stage recovered slowly over 1 year after onset, while the 2 patients showed the normal NSE and S-100b levels and recovered within 4 months. In 6 patients, the NSE and/or S-100b were slightly or moderately increased in the acute stage. They recovered from 1.5 to 11 months after onset, and the two patients showing very early recovery have the remarkably increase of S-100b in the recovery stage. These results suggest that CSF NSE and S-100b may be useful biochemical markers for estimation of prognosis in GBS patients.

Adolescent↗
PubMed1990

[Neuron-specific enolase and S-100 protein levels in cerebrospinal fluid of patients with cervical spondylosis and ossification of posterior longitudinal ligaments].

We examined the levels of neuron-specific enolase (NSE) and S-100 protein in the cerebrospinal fluid (CSF) in 39 cases of cervical spondylosis (CS), in 16 cases of ossification of posterior longitudinal ligaments (OPLL), and in 29 control subjects by means of highly sensitive enzyme immunoassay methods. The levels (mean +/- SD) of NSE and S-100 protein in the control subjects, CS cases, and OPLL cases were shown as follows: NSE = 4.7 +/- 2.1, 8.0 +/- 3.4, 6.0 +/- 3.1 ng/ml, S-100b = 0.42 +/- 0.22, 0.72 +/- 0.40, 0.67 +/- 0.27 ng/ml, respectively. CS patients with a muscle atrophy of upper limbs showed a rise in NSE levels and this was especially seen in cases of cervical spondylotic amyotrophy (CSA). There were positive correlations between the distance of the A-P diameters of the spinal canal and the amount of NSE in OPLL cases (r = -0.6915, p less than 0.01). CS patients with severe spinal cord compressions demonstrated by myelo CT showed higher levels of NSE and S-100b. These results suggest that NSE, S-100 protein can be used as reliable markers to evaluate the damage of the spinal cord in CS and OPLL.

Adult↗
PubMed1989

Neuronal modulation of Schwann cell glial fibrillary acidic protein (GFAP).

Adult rat sciatic nerves contain cytoskeletal peptides that resemble CNS glial fibrillary acidic protein (GFAP) in immunoreactivity and molecular weight. Immunohistological examination of teased nerve fascicles indicated that these peptides are expressed selectively by Schwann cells related to small axons. Radiolabelled mouse and rat CNS GFAP cDNA probes hybridized with a single, 2.7 kb RNA band in Northern blots prepared from total RNA from both rat sciatic nerve and rat brain. Sciatic nerve GFAP mRNA was detectable by this means in adult, 2 month, or 21 day postnatal rats, but not in 3,6, or 10 day postnatal rats. Sciatic nerve transection caused a marked reduction in the level of GFAP mRNA in the axotomized distal stump. We conclude that Schwann cell synthesis of GFAP is developmentally regulated and that Schwann cells, unlike astroglia, require continued trophic input from small axons in order to express GFAP.

Aging↗
PubMed1987

Cultured rat Schwann cells express low affinity receptors for nerve growth factor.

Schwann cell cultures prepared from postnatal Sprague-Dawley rat sciatic nerves were used to demonstrate the presence of specific receptors for the beta-subunit of nerve growth factor (NGF) on rat Schwann cells. Indirect immunofluorescence microscopy with a monoclonal antineuronal NGF receptor (NGFR) antibody indicated that NGFR antigen was expressed on the surface of Schwann cells but not of endoneurial fibroblasts. Studies with 125I-NGF confirmed this distribution of NGFR in the cultures and showed that the Schwann cell NGFR had a single NGF binding affinity (Kd of 1.8 x 10(-9) M). 125I-NGF binding by the cultured Schwann cells increased with time in vitro, reaching a plateau level on the 4th day, but decreased with increasing age, reaching 40% of the neonatal value in Schwann cells isolated from 12-day-old rats. Treatment of the cultures with NGF did not alter Schwann cell phenotype, survival or proliferation.

Animals↗
PubMed1987

Serum creatine kinase isoenzymes in Duchenne muscular dystrophy determined by sensitive enzyme immunoassay methods.

Serum levels of creatine kinase (CK) isoenzymes (MM, MB, and BB) were measured by sensitive enzyme immunoassay (EIA) methods in 50 patients with Duchenne muscular dystrophy (DMD) and in 39 controls. MM, MB, and BB levels in DMD patients were higher than in controls, and these three levels decreased with advancing age of DMD patients. Serum MB levels showed a good correlation with serum levels of carbonic anhydrase III (CA-III), but correlated poorly with electrocardiographic findings, suggesting that the main origin of serum MB in DMD is skeletal muscle rather than cardiac muscle.

Adolescent↗
PubMed1985

Highly sensitive enzyme immunoassay for human creatine kinase BB isozyme.

A sensitive sandwich-type enzyme immunoassay method for measurement of brain-type isozyme of human creatine kinase (CK-BB) was developed using purified antibodies specific to the B subunit. The assay system consisted of polystyrene balls with immobilized antibody F(ab')2 fragments and the same antibody Fab' fragments labelled with beta-D-galactosidase from Escherichia coli. The assay was highly sensitive and 1 pg of CK-BB was measurable. The assay was specific to the B subunit of creatine kinase (CK-B), and it cross-reacted about 25% with CK-MB, the heart-type isozyme. However, the assay showed no cross-reactivity with CK-MM, the muscle type-isozyme or with neuron-specific gamma gamma enolase. Coefficients of variation in within-run and between-run precision studies for serum CK-B were less than 8%. Serum CK-B levels in healthy adults of various ages (16-59 yr old) ranged from 0.25-1.44 ng/ml, whereas the CK-B concentrations in children (less than 10 yr old) were relatively high, ranging from 1.3-7.4 ng/ml. The CK-B levels in the cerebrospinal fluids (CSF) could be determined by the present method, and they ranged from 0.10-0.76 ng/ml in the samples from patients with non-neuronal disorders. Determination of immunoreactive CK-B in the extracts of various human tissues confirmed previous reports that CK-B was distributed at high concentrations in the central nervous tissue, prostate, uterus, bladder, gastrointestinal tract and heart muscle.

Adult↗
PubMed1985

Immunohistochemical demonstration of carbonic anhydrase III and muscle-specific enolase in paraffin-embedded human skeletal muscle sections.

We have demonstrated the histochemical fiber types of human skeletal muscle in paraffin sections by the immunohistochemical method, together with compatible observations previously made in frozen sections that carbonic anhydrase III is mainly localized in type 1 fibers (Shima et al. 1983), and muscle-specific enolase in type 2 fibers (Ibi et al. 1983). This method is useful to analyze the fiber types when frozen muscle samples at biopsy or autopsy cannot be obtained.

Animals↗
PubMed1985

Serum carbonic anhydrase III in progressive muscular dystrophy.

Serum carbonic anhydrase III (CA-III) levels were determined by means of an enzyme immunoassay method and compared with serum creatine kinase (CK) and muscle-specific enolase (MSE) levels in 143 patients with four types of progressive muscular dystrophy (PMD), namely, Duchenne muscular dystrophy (DMD), limb-girdle dystrophy, facioscapulohumeral dystrophy and congenital dystrophy. Serum CA-III levels were raised in the majority of patients, especially in those with DMD. In DMD patients, the gradual decline in the CA-III level was observed with age. High correlations were found between CA-III, CK and MSE levels. The frequency of cases with elevated CA-III levels was the same as or greater than that of elevated CK or MSE levels in four types of PMD. These results suggest that serum CA-III may be a useful marker of muscle disease.

Adolescent↗
PubMed1984

Distribution of immunoreactive carbonic anhydrase III in various human tissues determined by a sensitive enzyme immunoassay method.

A sensitive sandwich enzyme immunoassay method for measurement of carbonic anhydrase III (CA-III) was established by use of purified antibodies to CA-III. The assay system consisted of polystyrene balls with immobilized antibody F(ab')2 fragments and the same antibody Fab' fragments labeled with beta-D-galactosidase from E. coli. The assay was highly sensitive and pg levels of CA-III were measureable. Coefficients of variation in within-run and between-run precision studies for serum CA-III were less than 10%. Serum CA-III levels in healthy subjects of various ages ranged from 0.8 to 24 ng/ml. Concentrations of immunoreactive CA-III in the extracts of various human tissues were also determined. Tissues composed of striated muscle contained more than 10 micrograms/mg protein of CA-III, whereas other tissues, including heart muscle, contained less than 0.5 microgram/mg protein. These results were consistent with other data showing that serum CA-III levels were raised in patients with progressive muscular dystrophy but not in those with acute myocardial infarction.

Adolescent↗
PubMed1984

Serum muscle-specific enolase in progressive muscular dystrophy and other neuromuscular diseases.

Serum muscle-specific enolase ( MSE , beta beta and alpha beta enolases) levels were determined in 162 patients with progressive muscular dystrophy (PMD) and other neuromuscular diseases by means of an enzyme immunoassay method. The relationships were examined between serum MSE , creatine kinase (CK) and other markers of muscle disease. Serum MSE was strikingly increased in Duchenne muscular dystrophy, and this elevation was more prominent in younger patients. Serum MSE was also increased in other types of PMD and certain other diseases. Serum MSE showed the highest correlation with CK. In the PMD group, the frequency of cases with elevated MSE was the same as in CK. These results indicated that serum MSE may well be a specific marker of muscle disease on a par with CK.

Adolescent↗