Biomedical subjects

S Kikuchi

Publications and source records attributed to S Kikuchi.

At least 235 records · Page 13Linked to original sources

PubMed1997

Tumor necrosis factor enhancement of transient outward potassium currents in cultured rat cortical neurons.

The effect of recombinant human tumor necrosis factor-alpha (TNF) on voltage-gated membrane currents of cultured neurons derived from embryonic rat cerebral cortex was studied using the whole-cell patch-clamp technique. Treatment of neurons with TNF resulted in an increase in outward potassium current density, dependent upon the concentration of TNF and the incubation time, without affecting other membrane currents such as barium and N-methyl-D-aspartate (NMDA). Long exposures (12-48 hr) to TNF (10-100 ng/ml) increased transient outward potassium current (A-current) density without affecting the parameters of activation and inactivation of the current. Prolonged exposures to TNF diminished its increasing effect on the A-current. Since the increase of A-current density induced by TNF is inhibited by both the anti-TNF receptor antibody and cycloheximide treatment, the effect of TNF might be mediated through receptors and by de novo synthesis of the channel protein itself and/or modulating proteins associated with the channel activities. Results indicate that phosphatidylcholine-specific phospholipase C and protein kinase C, but not ceramide, are involved in the signal transduction. In toxicological experiments, TNF had no neurotoxicity. Moreover, a 12 hr pretreatment of TNF protected neurons against NMDA-induced neurotoxicity. This protective effect of TNF was cancelled by 4-aminopyridine, an A-current blocker, suggesting that the increase of A-current densities induced by TNF contributes to the neuroprotection.

Animals↗

PubMed1997

Experimental disc herniation: evaluation of the natural course.

STUDY DESIGN: Changes in L7 nerve root conduction velocity and changes in appearance on magnetic resonance study of the L6-L7 intervertebral disc in the dog were assessed for 2-6 months after an experimental disc herniation was performed. OBJECTIVES: To assess the time-related changes of nerve conduction velocity and magnetic resonance changes of the intervertebral discs. SUMMARY OF BACKGROUND DATA: It is known that nucleus pulposus may induce nerve root morphologic and functional changes when applied epidurally. However, it is not known whether such changes are reversible. METHODS: The spinal canal was opened by laminotomy of the upper part of the L7 lamina and the lower part of the L6 lamina on the left side. The L7 nerve root was gently retracted (sham) or the disc was punctured and injected with saline to produce herniation of the nucleus pulposus during the retraction time (herniation). After 1 day to 2 months, nerve root conduction velocity was determined by local electrical stimulation. Six dogs had the herniation or the sham procedure, and the L6-L7 disc was studied by magnetic resonance imaging at various times up to 6 months after the procedure. RESULTS: Decrease in nerve conduction velocity reached a maximum after 7 days and recovered to baseline level fully within 2 months. Although there was a clear reduction-recovery pattern, the difference in conduction velocity compared with that of the sham group was statistically significant after only 7 days. Disc degeneration started in the herniated discs within 7 days after the herniation procedure. However, none of the experimentally induced disc herniations were visualized by magnetic resonance imaging 7 days after the procedure. In no case was there subsequent nerve root compression. In one case, disc protrusion was visible 6 months after the herniation procedure. CONCLUSIONS: The results demonstrate for the first time that nucleus pulposus-induced nerve root injury reverses in 2 months and that it may be present without simultaneous nerve root compression, as confirmed by findings in magnetic resonance imaging. The previously described nucleus pulposus-induced nerve root changes may therefore be of clinical importance, and experimental studies of these mechanisms will probably be relevant for expanded understanding of the pathophysiologic mechanism behind sciatica that is caused by disc herniation.

Animals↗

PubMed1997

Clinical analysis of two-level compression of the cauda equina and the nerve roots in lumbar spinal canal stenosis.

STUDY DESIGN: This study is a prospective, clinical study assessing the efficacy of selective decompression of the responsible level in two-level stenosis in accordance with neurologic findings defined by the gait load test, and functional diagnosis based on selective nerve root block. OBJECTIVE: To clarify the clinical features of two-level stenosis regarding the neurologic level responsible for the symptoms, neurogenic intermittent claudication, and the outcome of selective decompression. SUMMARY OF BACKGROUND DATA: Experimental studies have indicated that double-level compression of the cauda equina induces a more severe impairment of nerve function than does single-level compression. However, few studies have focused on the clinical importance of two-level stenosis. The clinical effects of two-level stenosis on the cauda equina and nerve roots are unknown. METHODS: A total of 81 patients with lumbar spinal canal stenosis due to spondylosis and degenerative spondylolisthesis were divided into two groups, two-level stenosis at L3-L4 and L4-L5, and one-level stenosis at L4-L5, based on myelography. The types of neurogenic intermittent claudication, the level responsible for neurologic findings, and the postsurgical outcome were compared between both groups. The level responsible for the symptoms in two-level stenosis was determined in accordance with neurologic findings on the gait load test and functional diagnosis based on a selective nerve root block. All patients underwent a prospective, selective decompression at the neurologically responsible level only. The average follow-up period was 4.6 years (range, 1-8 years). RESULTS: The patients with two-level stenosis more frequently had cauda equina symptoms than those with one-level stenosis, except patients with degenerative spondylolisthesis. It was therefore assumed that two-level stenosis was associated with cauda equina impairment, Changes in neurologic condition before and after the gait test were observed in four patients with two-level stenosis. Finally, for 28 patients with two-level stenosis, the levels responsible for the neurologic symptoms were the caudal level (L4-L5) in 22 patients, the cranial level (L3-L4) in 1 patient, and both cranial and caudal levels (L3-L4 and L4-L5) in 5 patients. All stenotic levels on the myelogram were not always symptomatic in two-level stenosis. However, in one-level stenosis, all of the responsible levels completely corresponded to the myelogram. Selective decompression only at the neurologically responsible level improved neurogenic intermittent claudication in all patients. The asymptomatic levels at which the stenotic condition was left unchanged at surgery did not become symptomatic at follow-up; in addition, there was no significant difference in the postoperative outcome between two-level stenosis and one-level stenosis. CONCLUSIONS: Two-level stenosis in patients with lumbar spondylosis is associated with production of cauda equina lesions. The gait load test provides information regarding changes in symptoms and neurologic condition during exercise. The responsible levels should be determined based on neurologic findings after the gait load test and a selective nerve root block. It is uncommon for both stenotic levels to be symptomatic in patients with two-level stenosis. Less invasive surgery such as selective decompression for the responsible level in patients with two-level stenosis is a useful technique with a good potential for long-term success.

Aged↗

PubMed1997

The contribution of endogenous mono-ADP-ribosylation to kindling-induced epileptogenesis.

We examined the alteration of endogenous mono ADP-ribosylation in the hippocampus of amygdaloid kindled rats to clarify the neurochemical basis of epilepsy. A significant increase of the ADP-ribosylation on the 38 kDa protein was observed in the hippocampal membrane of the kindled rat. Several antiepileptics (phenytoin, phenobarbital, carbamazepine, sodium valproate) significantly decreased the ADP-ribosylation on the 38 kDa protein and effaced the increase in the kindled group. The ADP-ribosylation was largely increased by sodium nitroprusside, a nitric oxide generating compound, in both the kindled and control groups. Carbamazepine could not affect the ADP-ribosylation in the presence of sodium nitroprusside. Twenty amino acids from the N-terminus of the ADP-ribosylated 38 kDa protein were determined by sequential analysis. The sequence was completely identical to that of glyceraldehyde-3-phosphate dehydrogenase. These results indicate that the endogenous mono-ADP-ribosylation which increased in the kindled group and decreased by the antiepileptics might be a specific reaction associated with the mechanisms of epileptogenesis.

Adenosine Diphosphate Ribose↗

PubMed1997

Expression of wild-type p53 tumor suppressor gene and its possible involvement in the apoptosis of thyroid tumors.

A good prognosis is often achieved in patients who have undergone treatment for human papillary carcinoma of the thyroid. On the assumption that this may be partly attributable to an apoptotic tendency of this special type of tumor, we measured DNA fragmentation, cell death by enzyme-linked immunosorbent assay (ELISA), and the expression of apoptosis-related genes. DNA fragmentation occurred more extensively in malignant tumor cells than in benign thyroid tumors or normal thyroid tissue, as examined by agarose gel electrophoresis and confirmed by the quantitative method using an ELISA kit. Although only expression of the tumor suppressor gene, p53, was increased in the tumor tissue, no expression of other genes, such as Fas, TNF, c-myc, c-fos or bcl-2, was observed in the normal, benign, or malignant tumor tissues, indicating that the roles of these gene functions, if any, were minimal in these tissues. Since p53 is closely related to cellular apoptosis and no point mutation was observed in the transcripts expressed by malignant cells, apoptosis and/or the production of an angiogenesis inhibitor induced by wild-type p53 molecules may be related to the favorable prognosis of patients treated for papillary carcinoma of the thyroid.

Apoptosis↗

PubMed1997

Dominantly inherited leukodystrophy showing cerebellar deficits and spastic paraparesis: a new entity?

We studied a dominant hereditary disorder showing progressive spastic paraparesis. The symptoms began in early childhood, with cerebellar deficits and mild mental deterioration, and the subsequent appearance of limb spasticity resulted in severe disability in the 3rd-4th decades of life. None of the patients were associated with any somatic abnormalities. Brain MRI showed diffuse white-matter involvement in all affected patients, but not in unaffected siblings. Although dominant, recessive, or X-linked leukodystrophies cause similar clinical features, our family did not show any known biochemical or gene deficits characteristic of these disorders. The clinical, radiological, and biochemical findings of this family are reported and suggest a possible novel genetic disorder.

Adult↗

PubMed1997

Anti-nuclear antibodies and the optic-spinal form of multiple sclerosis.

We found anti-nuclear antibodies (ANA) (1:20 or higher) in sera from 11 of 16 patients with a diagnosis of the optic-spinal form of multiple sclerosis (OpS-MS) and 13 of 59 patients with other forms of MS (other MS), both rates being significant (P = 0.0004). Six of the OpS-MS patients had a high level of ANA (1:80 or higher), while levels were high in only three of the other MS patients, showing a significant difference (P = 0.0022). Titres of ANA were significantly higher in OpS-MS patients than in other MS patients (P < 0.0001). There was no relationship between the presence of ANA and age in OpS-MS patients, while patients with were older than those without high ANA levels among other MS patients. ANA-positive rate and titres were significantly higher in OpS-MS patients than in sex- and age-matched other MS patients. These results support the concept that OpS-MS constitutes a distinct subgroup among patients with a clinical diagnosis of MS and may indicate that systemic dysregulation of the inflammatory or immune response is more common in OpS-MS patients; the possible pathogenetic relevance of ANA-associated vasculopathy to some patients with a clinical diagnosis of OpS-MS should be considered.

Adult↗

PubMed1997

Use of internal thoracic artery as a systemic-pulmonary artery shunt.

Numerous technical and physiologic problems have been described with conventional systemic-pulmonary artery shunts. We report the case of a 1-year-old girl in whom the internal thoracic artery was used to create a systemic-pulmonary artery shunt after the failure of a previous Blalock-Taussig shunt. The internal thoracic artery as an alternative systemic-pulmonary artery shunt may offer several potential advantages and can be used successfully to improve cyanotic heart disease in selected cases.

Anastomosis, Surgical↗

PubMed1997

Identification of cell types producing RANTES, MIP-1 alpha and MIP-1 beta in rat experimental autoimmune encephalomyelitis by in situ hybridization.

The chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta are members of the beta-family of chemokines and potent chemoattractants for lymphocytes and monocytes. To investigate the factors which regulate lymphocyte traffic in experimental autoimmune encephalomyelitis (EAE), we studied, by in situ hybridization analysis, the kinetics of mRNA expression and the potent cellular sources of RANTES, MIP-1 alpha and MIP-1 beta in the central nervous system (CNS) during the course of EAE. RANTES-positive cells appeared in the subarachnoid space and infiltrated the subpial region at around day 10, increased to a peak at days 12-13 and then decreased following the resolution of the acute phase of EAE, though elevated RANTES message expressions still remained on chronic subclinical stage. Most of RANTES positive cells were identified as T-lymphocytes located mainly around blood vessels, by combined studies of in situ hybridization and immunohistochemistry. The remainder of the RANTES-positive cells were astrocytes and macrophages/microglia. MIP-1 alpha and MIP-1 beta mRNA-positive cells appeared around day 10, increased further on days 12-13 and then gradually decreased. Most of the MIP-1 alpha- and MIP-1 beta-positive mononuclear cells were located around blood vessels. The kinetics of RANTES, MIP-1 alpha and MIP-1 beta expression paralleled those of the recruitment of infiltrating inflammatory cells and disease severity. Our observations support the possibility that chemokine production by T-cells, macrophages and astrocytes lead to the infiltration of inflammatory cells into the CNS parenchyma during the acute phase of EAE.

Animals↗

PubMed1997

Role of extracellular signal-regulated protein kinases 1 and 2 in oligodendroglial process extension.

The relationship between extracellular signal-regulated protein kinase (ERK) activation and process extension in cultured bovine oligodendrocytes (OLGs) was investigated. Process extension was induced through the exposure of cultured OLGs to phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), for various intervals. During the isolation of these OLGs from bovine brain, the original processes were lost. Therefore, any reinitiation of process extension via PMA stimulation was easily discemible through morphological monitoring. It was found that exposure of OLGs to PMA for 10 min was enough to induce OLG process extension 24-72 h later. Furthermore, this extension was still evident at least 1 week after the initial PMA stimulation, indicating that OLGs do not need continuous PKC activation to sustain process extension. Control and PMA-stimulated OLGs were also subjected to immunocytochemistry using an anti-ERK antibody selective for the mitogen-activated protein kinases p42 Erk2 (ERK2) and p44 Erk1 (ERK1) isoforms. ERK immunoreactivity in the nucleus was evident after PMA stimulation of OLGs but not in control OLGs. In parallel experiments, the control and PMA-stimulated OLGs were purified by Mono Q fractionation and subjected to ERK phosphotransferase assays using [gamma-32P]ATP and either myelin basic protein (MBP) or a synthetic peptide substrate based on the Thr97 phosphorylation site in MBP. These assays indicated that in PMA-treated OLGs, ERK activation was at least 12-fold higher than in control OLGs. Anti-ERK and anti-phosphotyrosine western blots of the assay fractions verified an enhanced phosphorylation of ERK1 and ERK2 in PMA-treated fractions relative to control fractions. When OLGs were pretreated for 15 min with the ERK kinase (MEK) inhibitor PD 098059 before PMA stimulation, they exhibited a 67% decrease in ERK activation as compared with cells treated with PMA alone. Furthermore, these MEK inhibitor-pretreated cells were still viable but showed no process extensions up to 1 week later. Therefore, we propose that a threshold level of ERK activity is required for the initiation of OLG process extension.

Animals↗

PubMed1997

Shift work and risk factors for coronary heart disease in Japanese blue-collar workers: serum lipids and anthropometric characteristics.

This study was conducted to determine if there is an association between shift work and risk factors for coronary heart disease (CHD) in Japanese male blue-collar shift workers. Health check-up data on serum lipid concentration and anthropometric indices of 33 three-shift workers and 27 two-shift workers were compared with those of day workers. The average years in age of the shift workers and day workers were 34.5 (SD = 7.1) and 32.7 (SD = 7.6), respectively. Serum total cholesterol levels of three-shift, two-shift and day workers were 5.70 (SD = 1.19) mmol/l, 4.81 (SD = 1.01) mmol/l, 4.98 (SD = 0.95) mmol/l, respectively, and the cholesterol levels of three-shift workers were significantly higher than the other workers (p < 0.05). In addition, the abdominal to hip circumference ratios were 0.905 (SD = 0.060) for three-shift workers and 0.877 (SD = 0.054) for day workers, with a significant difference (p < 0.05). In the present Japanese population, three-shift workers had higher risks of CHD than day workers, which was characterized by higher levels of serum total cholesterol and tendency to central obesity. These findings held when lifestyle factors were taken into account.

Adult↗

PubMed1997

Methods to persuade higher management to invest in health promotion programmes in the workplace.

This study was conducted to find effective methods to persuade higher management to invest in workplace health promotion (WHP) programmes. The study included 639 occupational health professionals selected from the directory of the Japan Society for Occupational Health. A questionnaire survey was mailed to health professionals throughout Japan in 1992, and all respondents were asked to identify themselves. We received 242 replies, which constituted a response rate of 38%. Eighty-one per cent of the respondents had attempted to persuade higher management to implement a WHP programme. Health professionals frequently presented their case to higher management through a safety and health committee (SHC), and advice provided at the SHC was perceived to be the most effective method by occupational nurses (ONs) and safety and health supervisors (SHSs). This method was rated second by occupational physicians (OPs), who thought recommendations from OPs stipulated by the Industrial Safety and Health Law to be most effective. Statistics on medical examinations constituted the data most frequently used to persuade higher management, followed by reports on worksite inspections and health care plans. Nearly 90% of OPs and 80% of ONs and SHSs felt that the above methods were fairly successful.

Health Promotion↗

PubMed1997

Spinocerebellar ataxia type 1 and familial spontaneous pneumothorax.

We report two siblings with spinocerebellar ataxia type 1 (SCA1) who experienced frequent episodes of spontaneous pneumothorax. Radiologic findings indicated underlying degenerative changes in the lungs. This suggests a possible pathophysiologic relationship between SCA1 and familial occurrence of spontaneous pneumothorax.

Adult↗

PubMed1997

[Effective low-dose amiodarone therapy for ventricular tachycardia complicated with ischemic heart disease and poor left ventricular function in an elderly patient].

A 71-year-old man who had ischemic heart disease with poor left ventricular function and ventricular tachycardia was admitted to hospital for evaluation. Cardiac catheterization was performed on August 19, 1996, and right coronary arteriography revealed total occlusion at segment 3. Left coronary arteriography revealed total occlusion at segment 6, and a lesion at segment 13 was 75% occluded. Partial collateral flow from the right ventricular branch to the left anterior descending artery was demonstrated, and the left ventricular ejection fraction was 24%. Recurrent ventricular tachycardia followed by pre-syncope occurred from August 23, 1996, and the patient underwent emergency coronary artery bypass surgery to the left anterior descending artery and circumflex artery using saphenous vein grafts. Ventricular tachycardia followed by pre-syncope occurred frequently after the bypass surgery, and antiarrhythmic agents (Vaughan Williams classification Ia and Ib groups) were ineffective. He received amiodarone (100 mg/day after a loading dose of 200 mg/day for 2 weeks) from September 6, 1996. His symptoms of arrhythmia decreased, and side effects have not been observed. Low-dose amiodarone was effective in this case of ischemic heart disease with left ventricular dysfunction and sustained ventricular tachycardia.

Aged↗

PubMed1997

[Analysis of Parkinson's disease and related syndromes using 123I-IMP-SPECT with the ARG method].

We studied regional cerebral blood flow (rCBF) in 8 patients with non-demented Parkinson's disease (PD). 1 patient with progressive supranuclear palsy (PSP), 1 patient with multiple system atrophy (MSA), and 7 normal control subjects using single photon emission computed tomography (SPECT) with the IMP-ARG method. Regions of interest were studied in the cerebral cortex (upper frontal, lower frontal, temporal, occipital, parietal), thalamus, basal ganglia, and cerebellum. In patients with PD, rCBF was normal in 4/8, and decreased in occipital lobe in 4/8. In patient with PSP, rCBF was decreased in the upper and lower frontal lobes, and in the cerebellum. In patient with MSA, rCBF was diminished in the cerebellum. The results of our study were almost compatible with the conventional rCBF study by positron emission tomography (PET), however, the decrease of rCBF in occipital lobe had rarely been reported, suggesting that might be related to visuospatial dysfunction in Parkinson's disease.

Aged↗

PubMed1997

[Transient hyperphosphatasemia observed in a boy with acute lymphoblastic leukemia].

A detailed time course of alkaline phosphatase (ALP; EC3.1.3.1) activity of transient hyperphosphatasemia (TH) in a 9-year-old boy with acute lymphoblastic leukemia (ALL) is described. The patient's serum ALP activity rose transiently to 49 times the upper limit of normal adult, without any evidences of hepatic and bone disease. The half-life of ALP activity was calculated about 10 days. We characterized ALP isoenzymes by usual electrophoresis using cellulose acetate membrane (Titan III iso-vis) and polyacrylamide disc gel (AlkPhor), and isoelectric focusing using polyacrylamide slab gel. The former two methods showed typical two bands (fast-alpha 2 and alpha 2 beta bands) and the latter one method revealed more basic bands of liver and bone, suggesting the extensive sialylation. The patient complained fever and diarrhea. Enterococcus faecium was detected from his stool. Etiologically, two more patients in the same ward showed TH in the same period. It suggested TH would be occurred by infectious states. Awareness of such benign forms of hyperphosphatasemia not related to malignancy will aid the physician in the differential diagnosis of elevated ALP activity.

Alkaline Phosphatase↗

PubMed1996

Incision of the anulus fibrosus induces nerve root morphologic, vascular, and functional changes. An experimental study.

STUDY DESIGN: The effects on nerve root structure, vasculature, and function after incision of the adjacent disc was studied in a dog model. OBJECTIVES: To see if only incision of the disc per se is sufficient for inducing similar changes. SUMMARY OF BACKGROUND DATA: It is well known that nucleus pulposus will induce nerve root structural and functional changes in experimental situations. In these previous studies, relatively large amounts of nucleus pulposus were applied. METHODS: The left L7 nerve root was exposed and mobilized in 10 dogs. In five dogs, the adjacent L6-L7 disc was incised, and in five other dogs, the disc was not incised. After 7 days, nerve conduction velocity was recorded, and specimens were obtained for histologic evaluation. RESULTS: The nerve conduction velocity was significantly lower in the incision group (13 +/- 14 m/sec) compared with the nonincision group (73 +/- 5 m/sec). Structural changes of the axons were more pronounced in the incision group, however, the degree and distribution was too limited to fully account for the neurophysiologic reactions observed. There aims were obvious signs of capillary stasis with an increased number and diameter of the intraneural capillaries in the incision group. CONCLUSIONS: The present study indicated that incision of the anulus fibrosus is sufficient to induce significant morphologic and functional changes and that vascular mechanisms may be of importance for the observed changes. These experimental data suggest that leakage of nucleus pulposus material from anular tears, with injury to adjacent nerve roots, might be one pathophysiologic mechanism in patients with low back pain and sciatica but with no radiologic or surgical evidence of disc herniation.

Animals↗

PubMed1996

Increased resistance to acute compression injury in chronically compressed spinal nerve roots. An experimental study.

STUDY DESIGN: Nerve conduction velocity was studied in the dog cauda equina subjected to chronic and, 1 week later, additional acute compression. OBJECTIVES: To model the situation of spinal stenosis by first inducing a controlled, chronic compression injury and then to add compression at various pressure levels to the already compressed cauda equina. SUMMARY OF BACKGROUND DATA: Previous models on nerve root and cauda equina compression have analyzed the effects of compression only on noninjured nerves. Clinically, the nerves that are compressed in spinal stenosis already are exposed to chronic compression. METHODS: The cauda equine in the lumbar spine of 10 dogs was first compressed by inflating a plastic balloon, which was placed in the spinal canal, to 10 mm Hg with a viscous substance or leaving it noninflated for control. After 1 week, a second plastic balloon, which was welded together with the first balloon, which had been located in the spinal canal for 1 week, was inflated to 50 or 100 mm Hg for 2 hours with 1.5 hour of recovery, and changes in the nerve conduction velocity were analyzed. Before inflation, baseline data, reflecting the effects of the chronic compression per se, were obtained. RESULTS: After 1 week, the nerve conduction velocity was significantly lower in the compressed cauda equina than in the control series, as an effect of the chronic compression. Additional compression demonstrated that the chronically compressed cauda equina was less susceptible to the compression-induced effects at 100 mm Hg compression. CONCLUSIONS: The data of the present study indicate that chronically compressed nerve roots acquire a tolerance to acute compression, which may indicate that there has been adaptation processes present in the compressed nerve tissue.

Acute Disease↗