Biomedical subjects

K Hasegawa

Publications and source records attributed to K Hasegawa.

At least 19 recordsLinked to original sources

PubMed1999

GATA-5 is involved in leukemia inhibitory factor-responsive transcription of the beta-myosin heavy chain gene in cardiac myocytes.

Leukemia inhibitory factor is a member of a family of structurally related cytokines sharing the receptor component gp130. Activation of gp130 by leukemia inhibitory factor is sufficient to induce myocardial cell hypertrophy accompanied by specific changes in the pattern of gene expression. However, the molecular mechanisms that link gp130 activation to these changes have not been clarified. The present study investigated the transcriptional pathways by which leukemia inhibitory factor activates beta-myosin heavy chain expression during myocardial cell hypertrophy. Mutation of the GATA motif in the beta-myosin heavy chain promoter totally abolished leukemia inhibitory factor-responsive transcription without changing basal transcriptional activity. In contrast, endothelin-1 responsiveness was unaffected by the GATA mutation. Among members of the cardiac GATA transcription factor subfamily (GATA-4, -5, and -6), GATA-5 was the sole and potent transactivator for the beta-myosin heavy chain promoter. This transactivation was dependent on sequence-specific binding of GATA-5 to the beta-myosin heavy chain GATA element. Cardiac nuclear factors that bind to to the beta-myosin heavy chain GATA element were induced by leukemia inhibitory factor stimulation. Last, leukemia inhibitory factor stimulation markedly increased transcripts of cardiac GATA-5, the expression of which is normally restricted to the early embryo. Thus, GATA-5 may be involved in gp130 signaling in cardiac myocytes.

Animals↗

PubMed1999

Inhibiting neuronal migration by blocking NMDA receptors in the embryonic rat cerebral cortex: a tissue culture study.

To investigate the role of the NMDA receptor on neuronal migration in the cerebral cortex, we performed a tissue culture study using embryonic rat brain. After we labeled progenitor cells in the ventricular zone of E16 cerebral cortex explants by [3H]thymidine, the explants were cultured for 48 h. Then distribution of labeled cells was evaluated autoradiographically. Blocking NMDA receptors by adding the NMDA receptor antagonist, (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801: 1 or 10 microM) or d(-)-2-amino-5-phosphonopentanoic acid (d-AP5: 100 microM) to the culture medium, caused significantly decreased distribution of labeled cells in the outer intermediate zone (control 14.2+/-5.5%, 1 microM MK-801 5.8+/-7.2%, 10 microM MK-801 3.6+/-1.4%, and d-AP5 8.6+/-4.0%; mean+/-S.D.). This suggests that blocking NMDA receptors inhibits neuronal migration in the cerebral cortex. Furthermore, the influence of decreased intracellular Ca2+ concentration on neuronal migration was examined by adding intracellular Ca2+ chelator, 1, 2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester (BAPTA-AM: 5 or 25 microM). This also resulted in inhibited neuronal migration. Therefore, it seems that neuronal migration in the cerebral cortex is regulated by intracellular Ca2+ concentration, which the NMDA receptor may influence.

2-Amino-5-phosphonovalerate↗

PubMed1999

The role of endothelin-converting enzyme-1 in the development of alpha1-adrenergic-stimulated hypertrophy in cultured neonatal rat cardiac myocytes.

BACKGROUND: Accumulating evidence suggests that the local synthesis of endothelin-1 (ET-1) plays a role in the development of heart failure in vivo. We investigated the role of endothelin-converting enzyme-1 (ECE-1), which mediates the conversion of big ET-1 to mature ET-1, in the development of alpha1-adrenergic-stimulated hypertrophy in cultured neonatal rat cardiac myocytes. METHODS AND RESULTS: Phenylephrine (PE) induced the expression of ET-1 in rat cardiac myocytes and accelerated the conversion of big ET-1 to ET-1. The ECE-1 mRNA levels were markedly increased 3 hours after PE stimulation (3.6-fold compared with saline stimulation, P<0.005). A specific ECE-1 antagonist, FR901533, inhibited the PE-stimulated increase in protein synthesis rate by 45% (P<0.05). As genetic markers for the hypertrophic response, FR901533 inhibited the PE-stimulated transcriptional activities of the 3.5-kb beta-myosin heavy chain promoter by 79% (P<0.01) but did not affect that of the 3.4-kb atrial natriuretic factor (ANF) promoter. In Bio14.6 Syrian cardiomyopathic hamsters, ventricular ET-1 and ANF mRNA levels did not correlate at 2 different stages. CONCLUSIONS: ET-1-independent pathways may mediate activation of the ANF gene program in ventricular myocytes both in vitro and in vivo. These results also indicate that the conversion of big ET-1 to ET-1 in rat cardiac myocytes is required for the development of alpha1-adrenergic-stimulated hypertrophy and beta-myosin heavy chain gene transcription.

Adrenergic alpha-Agonists↗

PubMed1999

Requirement of PEST domain tyrosine phosphatase PEP in B cell antigen receptor-induced growth arrest and apoptosis.

Signaling events leading to B cell growth or apoptosis are beginning to be unravelled, but detailed information is still lacking. To identify signaling molecules involved in B cell antigen receptor (BCR)-initiated pathways, we used the immature B cell line, WEHI-231, to investigate protein tyrosine phosphatases (PTP) whose expression was modulated by BCR ligation. Among the PTP cloned by reverse transcription-PCR, mRNA expression of the proline-, glutamic acid-, serine- and threonine-rich (PEST) domain phosphatase (PEP) was selectively elevated 3.1-fold within 3 h after anti-IgM antibody stimulation. In contrast, expression of another PEST domain phosphatase, PTP-PEST, was unaffected. Western blot analysis revealed that 71% of PEP was located in the cytosolic fraction, while 29% was in the membrane fraction. To examine the direct contribution made by PEP to BCR-initiated signal transduction, we transfected an antisense PEP cDNA into WEHI-231 cells. Two stable clones were established in which PEP expression was reduced by 34% and 47%, respectively. Strikingly, BCR-mediated inhibition of DNA synthesis was significantly rescued in the clones, and G1 phase cell cycle arrest and apoptosis were almost completely ablated. Considered collectively, these results indicate that PEP is a positive, crucial regulator in determining B cell fate triggered by BCR engagement.

Amino Acid Sequence↗

PubMed1999

Modified functional hemispherectomy in hemimegalencephaly.

We report a case of hemimegalencephaly in a 13-month-old girl successfully treated with modified functional hemispherectomy. Instead of total temporal lobectomy, medial temporal lobectomy with excision of the hippocampus and amygdala was carried out. The central region including the parasagittal tissue was preserved. A few days after the surgery seizures completely ceased. Administration of anticonvulsants was stopped 5 months after the surgery, and she has been seizure-free for 42 months.

Amygdala↗

PubMed1999

Upregulated expression of cardiac endothelin-1 participates in myocardial cell growth in Bio14.6 Syrian cardiomyopathic hamsters.

OBJECTIVES: The purpose of this study is to investigate the role of endogenous endothelin-1 (ET-1) in myocardial growth in Bio 14.6 Syrian cardiomyopathic hamsters (Bio). BACKGROUND: While ET-1, as a growth-promoting peptide, has been implicated in the development of secondary cardiac hypertrophy, the role of endogenous ET-1 in cardiac growth in primary myocardial disease is unknown. METHODS: We measured left ventricular ET-1 levels by a specific sandwich enzyme-linked immunosorbent assay. Furthermore, we examined the chronic effect of T0201, an ET type A receptor-specific antagonist. RESULTS: The ET-1 levels in the left ventricles were 1.8-fold higher (p < 0.0005) at 20 weeks and 6.4-fold higher (p < 0.0001) at 35 weeks in the Bio compared to age-matched control F1B hamsters (F1B). The Bio ET-1 levels in the lungs exhibited an only 1.3-fold elevation at 35 weeks. Immunohistochemistry demonstrated the localization of ET-1 mainly in the cardiac myocytes. The treatment with T0201 significantly reduced the heart weight/body weight ratio in the Bio, but did not affect the heart weight/body weight ratio in the F1B. Histologically, T0201 reduced the myocyte diameter of Bio to a level similar with that of F1B. However, T0201 did not affect the extent of fibrosis in Bio or F1B. CONCLUSIONS: The ET-1 level in the heart of cardiomyopathic hamsters increases in stage-dependent and organ-specific manners. Though myocyte degeneration and subsequent replacement fibrosis do not require an ET-1 pathway, the accelerated synthesis of ET-1 in the heart may contribute to the pathological growth of remaining myocytes in this animal model.

Animals↗

PubMed1999

Discrimination of two different clinical entities, acute-type and subacute-type, human fulminant hepatitis by peripheral blood lymphocyte subsets.

Human fulminant hepatitis tends to be classified into two groups: acute type (A-FH) and subacute type (S-FH). In order to define these two clinical entities more precisely, we examined and compared peripheral blood lymphocyte subsets in A-FH and S-FH patients. We found that S-FH patients had a higher prevalence of CD19+ B cells (31.1 +/- 7.6% in S-FH vs 12.7 +/- 3.7% in A-FH) and also a lower prevalence of CD3+T cells (50.2 +/- 8.7% in S-FH vs 65.6 +/- 10.5% in A-FH). Furthermore, by examining the absolute cell numbers of these subsets, we determined that their imbalance in S-FH was mainly due to a decrease in CD3+ T cells. Among several T cell subsets, the CD8+CD11b-T cell subset was elevated in A-FH and decreased in S-FH (6.1 +/- 2.1% in S-FH, 24.4 +/- 5.8% in A-FH, and 14.8 +/- 7.8% in control). Serial studies of two S-FH patients revealed that the imbalance of these lymphocyte subsets returned to their proper ratio together with the improvement of their liver injury. These results indicate that there might be a different immunological background between A-FH and S-FH.

B-Lymphocyte Subsets↗

PubMed1999

Simple fluctuation of Ca2+ elicits the complex circadian dynamics of cyclic AMP and cyclic GMP in Paramecium.

The circadian dynamics of cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) were simulated in Paramecium multimicronucleatum. The mathematical functions determined closely mimic the Ca2+ dependence of adenylate cyclase (AC) and guanylate cyclase (GC) activities as documented in P. tetraurelia. Patterns of cAMP concentration ([cAMP]), cGMP concentration ([cGMP ]), and the ratio [cGMP]/[cAMP] were calculated with respect to Ca2+ concentrations ([Ca2+]) fluctuating sinusoidally with a period of 24 hours at three different levels: low, medium, and high. The functions displayed varying patterns of [cAMP] characteristic for [Ca2+] fluctuating at each level, while patterns of [cGMP] and [cGMP]/[cAMP] almost paralleled [Ca2+] fluctuations. Similar patterns were observed for actual [cAMP] and [cGMP] measured during the light/dark cycle in P. multimicronucleatum, grown in axenic media additionally containing [Ca2+] at 25 (low), 100 (medium), or 400 (high) microM, respectively. The coincidence between simulated and measured fluctuations of [cAMP] and [cGMP] suggests that the circadian fluctuations of intracellular [Ca2+] primarily stimulate activities of AC and GC via their different degrees of Ca2+ dependence, which are ultimately responsible for the circadian spatiotemporal organization of various physiological functions in Paramecium.

Adenylyl Cyclases↗

PubMed1999

A patient with hypertrophic cardiomyopathy accompanied by right ventricular dilation of unknown cause.

Hypertrophic cardiomyopathy (HCM) is a disease characterized by an unknown cause of hypertrophy in the left or right ventricle. The dilated phase of HCM shows disease conditions resembling dilated cardiomyopathy, such as ventricular dilation, thin ventricular wall, and reduction of the ejection fraction. A patient presented with left ventricular concentric hypertrophy accompanied by right ventricular dilatation of unknown cause. Right ventricular endomyocardial biopsy specimens showed characteristic myocardial disarray. Therefore, there is the possibility that the patient had right and left ventricular HCM in the process toward the dilated phase, in which dilatation first occurred in the right ventricle.

Atrial Fibrillation↗

PubMed1999

[Pulmonary vein reconstruction for lung carcinoma].

Four cases of primary lung carcinoma (two squamous cell carcinomas and two adenocarcinomas) were performed right middle lobectomy combination with the reconstruction of upper pulmonary vein to remain the upper lobe. Lung carcinomas were in the right lobe and infiltrated to lower margin of upper pulmonary vein in all cases. After resection of the right middle lobe and an affected portion of upper pulmonary vein, the defect of the upper pulmonary vein was replaced with auto-pericardial graft in three cases, and the other one was closed by continuous suture of 5-0 plorene. Pathological classification of these four cases was stage IB in one patient, stage IIB in two and stage IV in one. All patients died from 6 to 53 months after operation (average: 31 months). Metastasis to distant organs was confirmed in all cases, so the prognosis of them was generally poor. Reconstruction of pulmonary vein may be feasible to avoid over resection of other lobes, because pulmonary function can be preserve as well as in the bronchoplasty.

Adenocarcinoma↗

PubMed1999

Growing and differentiating characterization of aortic smooth muscle cell line, p53LMAC01 obtained from p53 knock out mice.

Recently we have established an aortic smooth muscle cell line, p53LMAC01 obtained from p53 knockout mice. This cell line showed some differentiated properties which were accelerated by 5-azacytidine treatment [1]. In this study, further characterization of p53LMAC01 cell line was investigated according to cell growth and differentiation, and especially focused into the changes of cell feature, actin filaments' formation, and changes of intracellular calcium concentrations to sympathetic nerve transmitter, norepinephrine. While the cell feature was changed from flattened shape to extended form during 4 days, actin filaments were developing, arranging in parallel to longitudinal direction, and gathering under the surface membrane. In 11 days many cells died and detached from substrate, while actin filaments became poor except for the surface membrane in the remained cells. Appearance of calcium response to noradrenalin needed several days after passage as well as a morphological change of the cells for the extended form and development of actin filaments. The calcium response was maintained on 11 days, which coincided with the result that the cells hold actin filaments under the surface membrane. These results suggest that p53LMAC01 cell line maintains several differentiated characters of adult smooth muscle cell and that their expression needs several days after passage.

Animals↗

PubMed1998

Apolipoprotein E and antioxidants have different mechanisms of inhibiting Alzheimer's beta-amyloid fibril formation in vitro.

We compared the mechanisms of apolipoprotein E- (apoE-) and antioxidant- (AO-) mediated inhibition of beta-amyloid fibril (fA beta) formation in vitro, based on a nucleation-dependent polymerization model using fluorescence spectroscopy with thioflavin T. We first applied a kinetic plot to transform a sigmoidal time-course curve of fA beta formation from freshly prepared amyloid beta-peptides (A beta) into a straight line. Mathematical treatment of this plot demonstrated that the above-described sigmoidal curve is a logistic curve and provided us with a kinetic parameter t(1/2), the time when the rate of fA beta formation is maximum. t(1/2) of beta-amyloids (A beta) (1-42) and (1-40) were 18.7 +/- 1.7 min and 6.3 +/- 0.2 h, respectively (mean +/- SD, n = 3) and were independent of the initial A beta concentration examined. Although apoE extended t(1/2) of both A betas in a dose-dependent manner, AO did not. On the other hand, the final amount of fA beta formed was decreased by both apoE and AO dose-dependently. We then analyzed the effect of apoE and AO on the extension reaction of fA beta, based on a first-order kinetic model. Although apoE extended the time to proceed to equilibrium in a dose-dependent manner, AO did not. On the other hand, both apoE and AO dose-dependently decreased the final amount of fA beta formed. These results indicate that apoE and AO inhibit fA beta formation in vitro by different mechanisms and suggest the existence of multiple pharmacological targets for the prevention of fA beta formation.

Amyloid beta-Peptides↗

PubMed1998

Cardiac endothelin-1 plays a critical role in the functional deterioration of left ventricles during the transition from compensatory hypertrophy to congestive heart failure in salt-sensitive hypertensive rats.

BACKGROUND: To investigate whether endogenous ET-1 participates in an adaptive process of left ventricular hypertrophy (LVH) or a maladaptive process from LVH to congestive heart failure (CHF), we used a Dahl salt-sensitive (DS) rat model, in which systemic hypertension caused compensated concentric LVH at the age of 11 weeks followed by marked LV dilatation and global hypokinesis at the age of 17 weeks. METHODS AND RESULTS: By specific sandwich enzyme immunoassay, serum and myocardial ET-1 levels at the LVH stage were not elevated compared with age-matched Dahl salt-resistant (DR) rats, despite the marked increase of LV/body weight ratio (LV/BW). However, at the CHF stage, serum and LV ET-1 levels increased by 3. 8-fold and 5.4-fold, respectively. LV ET-1 contents had close relationships with the fractional shortening (r=0.763) and the systolic wall stress (r=0.858) measured by in vivo transthoracic echocardiography. Immunohistochemistry demonstrated that the remarkably increased ET-1 in LV is located mainly in cardiomyocytes. By competitive reverse transcriptase-polymerase chain reaction, LV prepro-ET-1 mRNA levels increased by 4.1-fold in CHF rats. We randomized 11-week-old LVH rats to chronic treatment with the endothelin receptor antagonist bosentan (Bos, 100 mg. kg-1. d-1, n=14), the alpha1-receptor antagonist doxazosin (Dox, 1 mg. kg-1. d-1, n=12), or vehicle (Cont, n=14). Bos treatment did not alter the LV geometry and function at 15 weeks; however, it attenuated the decrease of LV fractional shortening by 51% (P<0.01) without reducing the LV/BW at 17 weeks. Conversely, Dox, which decreased the blood pressure to the same extent as Bos, did not affect the progression of LV dysfunction. Bos (93%; P<0.0001 versus Cont) but not Dox (42%; P=0.8465 versus Cont) ameliorated the survival rate at 17 weeks (Cont; 36%). CONCLUSIONS: The accelerated myocardial synthesis of ET-1 contributes directly to LV contractile dysfunction during the transition from LVH to CHF. Unelevated levels of LV ET-1 at the established LVH stage and lack of effects on LV mass by chronic bosentan treatment suggest that myocardial growth is mediated through alternative pathways. These studies indicate that chronic ET antagonism may provide an additional strategy for heart failure therapy in humans.

Adaptation, Physiological↗

PubMed1998

Ultrafine flexible spinal endoscope (myeloscope) and discovery of an unreported subarachnoid lesion.

STUDY DESIGN: Introduction of a new diagnostic procedure and a report on its usefulness. OBJECTIVES: To introduce a new endoscope (myeloscope) developed for the examination of the spinal canal and to present a previously unreported subarachnoid condition as a cause of paraparesis revealed by it. SUMMARY OF BACKGROUND DATA: In spite of the availability of advanced imaging technology, there still exists a significant number of patients with spinal diseases in whom a diagnosis cannot be made. Direct visualization of the pathologic area is required in these patients. Recent advances in fiberoptics have made this possible. METHODS: The endoscope consisted of a fiberscope with an external diameter of 0.5, 0.9, or 1.4 mm. It was inserted into the subarachnoid space in the lumbar spine and carefully advanced cranially. Since 1987, this examination has been performed on 18 patients aged 7 to 69 years who had pain or other neurologic symptoms of unknown origin. RESULTS: The surface of the spinal cord, roots, properties of the arachnoid membrane, and small vessels could be observed clearly. The scope could be advanced as far as the upper cervical spine. Cotton-candy-like proliferation of fibrous tissue was identified by myeloscopy in four paraparetic patients who had clinical and radiologic features similar to those of a spinal cord herniation. The fibrous tissue beat on the spinal cord with the pulsation of the spinal fluid. Resection of the fibrous tissue with conventional surgery resulted in neurologic improvement. Complications included one case of meningitis in the early period and five cases of postspinal headache. No nerve injury was apparent. CONCLUSIONS: Myeloscopy provides detailed information about the subarachnoid space and even reveals dynamic conditions that cannot be identified during open surgery or at autopsy. It will bring new concepts to the diagnosis of spinal diseases.

Adolescent↗

PubMed1998

Vertebral pseudarthrosis in the osteoporotic spine.

STUDY DESIGN: Radiologic and operative findings of intravertebral cleft in the osteoporotic spine were investigated and the pathomechanism discussed. OBJECTIVES: To clarify the pathologic features of the intravertebral cleft. SUMMARY OF BACKGROUND DATA: Intravertebral "vacuum" cleft is one of the common radiographic findings in the osteoporotic spine. It is thought that the cleft is a rare lesion of an ununited fracture, or pseudarthrosis. Evidential findings of the disease, however, have never been reported. METHODS: Simple bone grafting was performed in five cases (average age, 76.8 years) of thoracolumbar intravertebral cleft in osteoporotic spine in patients who had been suffering from prolonged pain of the back or leg. Preoperative radiologic evaluation using flexion-extension radiograph and magnetic resonance imaging was performed in all patients. At operation, the cleft and the components of the structure were macroscopically and microscopically observed. The fluid content in the cleft was biochemically analyzed. RESULTS: In all patients, preoperative flexion-extension radiographs showed intravertebral instability at the location of the clefts that indicated gas density in three cases and water density in two cases. Magnetic resonance imaging showed that, for the most part, the cleft was low intensity on the T1-weighted image and high intensity on the T2-weighted scans, regardless of the radiographic findings. At operation, abnormal movement was observed at the cleft of the affected body, which was covered with hypertrophic membrane. The serous fluid within the cleft was aspirated before the excision of soft tissue. The thick membrane was excised and showed that the cleft was lined by smooth fibrocartilaginous tissue and the great degree of motion between the fracture ends that is consistent with the pathologic appearance of pseudarthrosis. CONCLUSIONS: The unstable cleft in the affected vertebral body of the osteoporotic spine with magnetic resonance findings of low intensity on the T1-weighted scans and high intensity on the T2-weighted scans suggests that the cleft is a false joint lined by fibrocartilaginous tissue with notable movement consistent with pseudarthrosis.

Aged↗

PubMed1998

Pathologic features of spinal disorders in patients treated with long-term hemodialysis.

STUDY DESIGN: Pathologic features of hemodialysis-associated spinal disorders were evaluated using preoperative radiographic images and histologic findings of the spinal lesions resected during surgery. OBJECTIVES: To investigate the pathology of hemodialysis-related spinal disorders and to determine the role of amyloidosis in the establishment of severe destruction of the spine. SUMMARY OF BACKGROUND DATA: The pathologic events leading to hemodialysis-associated spinal disorders are poorly understood. The distribution of amyloid deposits in the spine also has not been clarified. METHODS: Twenty patients with hemodialysis-associated spinal disorders were investigated regarding pathologic features of neural compression and spinal destruction. Preoperative radiographic images such as plain radiography, tomography, computed tomography, magnetic resonance imaging, and scintigraphy were assessed for the existence of an intracanal mass, hypertrophy of the ligamentum flavum, and destructive changes of the spinal components. Histologic examination also was conducted by light microscopy and scanning electron microscopy to determine the distribution pattern of amyloid deposits in the spinal components. RESULTS: Six patients with no destructive changes in the spine showed spinal canal stenosis. In the cervical spine, a main factor associated with spinal canal stenosis was the presence of intracanal amyloid deposits in three patients. In the lumbar spine, a main factor associated with spinal canal stenosis was hypertrophied ligamentum flavum in three patients. Destructive changes of the facet joints, intervertebral disc, and vertebral body were seen in the other 14 patients. Amyloid deposits were densely distributed at the enthesis of capsular fibers to the bone and in anular tears in the intervertebral discs. Vertebral end plates were destroyed by penetration of amyloid granulation into the vertebral body. Osteoclast activity in the destroyed vertebral bodies was enhanced, with no evidence of new bone formation. CONCLUSIONS: Amyloid deposits played an important role in the progression of spinal destruction and severe instability.

Adult↗

PubMed1998

Domain organization and functional analysis of Thermus thermophilus MutS protein.

MutS protein binds to DNA and specifically recognizes mismatched or small looped out heteroduplex DNA. In order to elucidate its structure-function relationships, the domain structure of Thermus thermophilus MutS protein was studied by performing denaturation experiments and limited proteolysis. The former suggested that T. thermophilus MutS consists of at least three domains with estimated stabilities of 12.3, 22.9 and 30.7 kcal/mol and the latter revealed that it consists of four domains: A1 (N-terminus to residue 130), A2 (131-274), B (275-570) and C (571 to C-terminus). A gel retardation assay indicated that T.thermophilus MutS interacts non-specifically with double-stranded (ds), but not single-stranded DNA. Among the proteolytic fragments, the B domain bound to dsDNA. On the basis of these results we have proposed the domain organization of T. thermophilus MutS and putative roles of these domains.

Adenosine Triphosphatases↗

PubMed1998

Kinesin and cytoplasmic dynein in spinal spheroids with motor neuron disease.

Kinesin and cytoplasmic dynein are two major molecular motors responsible for fast axonal transport. As visualized by immunohistochemistry with monoclonal antibodies, both motors were found to be distributed throughout the cell bodies, dendrites and axons of motor neurons in normal human spinal cords. Large axonal swellings, spheroids, in the spinal cords of patients with motor neuron disease showed massive accumulation of kinesin co-localized with highly phosphorylated neurofilaments. Of 114 spheroids in five spinal cords, 87% were stained heavily with the three anti-kinesin antibodies used in this study. Cytoplasmic dynein was scarce or absent in most of the spheroids. These findings suggest that kinesin selectively accumulates in the spheroids of motor neuron axons, causing disturbance of the machinery for anterograde fast axonal transport in motor neuron disease.

Aged↗