Biomedical subjects
Publications and source records attributed to I Akiguchi.
Two cases of intracranial malignant lymphoma with an atypical feature on CT scan are reported. Both patients presented subacute progressive dementia. CT scan showed high density lesion extending all the way along the ventricular wall, which was homogeneously enhanced and resembled severe ventriculitis. Differential diagnosis on CT scan is discussed.
To study the possible involvement of human T lymphotrophic virus type I (HTLV-I) or a related retrovirus in Japanese cases of multiple sclerosis (MS), we first performed a Western blot analysis with purified Ag of HTLV-I. Ten out of 31 MS patients (32.2%), 19 of 66 patients (28.8%) with other neurologic diseases, and 2 of 64 healthy blood donors (3.1%) had antibodies reactive with Ag corresponding to the group-specific Ag (gag) proteins (p15, p19, p24) on their sera. There were no significant differences between MS and other neurologic diseases concerning the patterns and the frequency. Second, we tried to establish T cell lines from PBMC of 22 MS patients with crude IL-2 without accessory cells, because HTLV-I-infected T cells can be immortalized in a high ratio under those conditions. Only one T cell line (MS-14C), however, could be maintained in long term culture. MS-14C and cultured T cells for 3 to 5 wk derived from MS patients were examined by Southern blot analysis under both stringent and low stringent conditions with HTLV-I as a probe. No HTLV-I related bands could be detected. By polymerase chain reaction examination, we also could not detect HTLV-I provirus genome in the fresh PBMC from 20 MS patients, although some of them had gag-reactive antibodies. Our data do not favor the hypothesis of HTLV-I or an HTLV-I-related human retrovirus in the etiology of MS.
We measured acetylcholinesterase (AChE) in the non-endplate region of rat muscle, documenting its intrinsic activity within muscle fibers, as well as the extrinsic level in the capillaries and endomysium. When each muscle was considered as a whole, intrinsic AChE activity detected within the fibers was stronger in the fast-twitch extensor digitorum longus than in the slow-twitch soleus. Analysis of individual muscle fibers also showed the same tendency with a higher value in the fast-twitch type II fibers than in the slow-twitch type I fibers. On the average, 73% of the fibers showed intermediate or strong enzymatic activity in the fast-twitch muscle, whereas 56% of the slow-twitch muscle had only low activity. Sectioning or ligation of the sciatic nerve resulted in nearly complete abolition of the enzyme in the non-endplate region of the denervated muscles within 7 days, suggesting that nerve transmission regulates AChE activity not only in the endplate, as is well known, but also outside this region. Human skeletal muscles showed the same pattern of AChE activity in the non-endplate region as seen in rat muscles.
Monoamine oxidase (MAO) histochemistry has been performed in brains from patients with dementia of Alzheimer type (DAT) and aged controls. Conspicuous MAO-positive cell clusters were frequently observed in the amygdala, hippocampus, and insular cortex in the brains of DAT. Double staining with glial fibrillary acidic protein immunohistochemistry revealed that the cluster-forming MAO-positive cells were astrocytes. Using Bielschowsky's method, Congo red and thioflavin S counterstaining, this astrocytic mass was shown to be associated with senile plaques. By the enzyme inhibition experiment, MAO activity in senile plaques was revealed to be of type B. The present results clearly indicate that MAO-B activity is expressed in fibrillary astrocytes in or around senile plaques, suggesting that these astrocytes metabolize exogenous amines in senile plaques.
Sixteen patients with HTLV-1 associated myelopathy (HAM) were examined for the presence of HTLV-1 provirus genome by Southern blot analysis of genomic DNA from peripheral blood mononuclear (PBM) cells. Random integration of the provirus was detected in 14 of 16 HAM patients. By contrast, the provirus genome could not be detected in 6 non-HAM HTLV-1 carriers, HAM patients were found to have significantly higher antibody titer to HTLV-1 in the sera compared with carriers. These features of HAM patients, i.e., detectable levels of provirus integration in PBM cells and high antibody titer to HTLV-1 in the sera, were noted in 2 wives of HAM patients with neurological signs and abnormalities. High anti-HTLV-1 antibody titer and detection of the provirus genome by Southern hybridizations may be useful for screening subclinical HAM cases and elucidating pathogenesis.
A patient with paramedian thalamic and midbrain infarcts developed palilalia.
We studied a 67-year-old female suffered from polymyositis associated with primary biliary cirrhosis. She was pointed out liver dysfunction by screening test. Alkaline phosphatase, transaminase, and IgM were increased. Antimitochondrial antibody and antinuclear antibody were positive. Liver biopsy showed cell infiltrations in Glisson's capsules and destruction of cholangioles, being diagnosed as primary biliary cirrhosis (Scheuer Stage I). Four years later she showed a muscle weakness of four extremities and admitted to our department. Neurological examination revealed a severe weakness and atrophy of both proximal and distal muscles. Deep tendon reflex was decreased on four extremities. Laboratory examination showed a creatine kinase level of 312 IU/L, alkaline phosphatase 238 IU/L, gamma-glutamyl-transpeptidase 140 IU/L, Igm 416 mg/dl, antimitochondrial antibody titer 1:320, and antinuclear antibody titer 1:320. Muscle biopsy findings were compatible with polymyositis. Electron microscopic examination disclosed diffuse increase of mitochondria in subsarcolemma and intermyofibrils. Until now eight cases with polymyositis associated with primary biliary cirrhosis have been reported, but electron microscopic examination of muscle has not been carried out. It is necessary to examine mitochondria of muscle and liver in patients with polymyositis associated with primary biliary cirrhosis for the elucidation of its etiology.
A case of herpes zoster myelitis improved with acyclovir was reported. A 71-year-old female showed a rash over the S2-4 dermatomes on the right side. After that, paraplegia and dysuria progressed. Patellar tendon reflex was exaggerated, but Achilles tendon reflex was normal. Babinski and Chaddock sign were bilaterally elicited. Superficial sense was markedly decreased below the Th12 dermatome. Vibration sense was slightly decreased but position sense was normal on the lower extremities. Cerebrospinal fluid analysis revealed pleocytosis, and an elevation of IgG and varicella-zoster virus antibody titer. Acyclovir (250 mg bid/day) was given for ten days. Paraplegia, sensory disturbance and dyschezia improved but dysuria did not. In this case acyclovir administration was started on the 18th day after the onset of myelopathy. Early initiation of acyclovir treatment might lead to recovery of dysuria. As the pathogenic mechanism of herpes zoster myelitis is considered to be direct viral invasion of the spinal cord with subsequent necrosis, early initiation of acyclovir treatment is necessary for the recovery.
Vascular changes occurring after stereotaxic injection of the excitatory neurotoxin kainic acid (KA) into the rat striatum were studied at various time intervals after the lesion using laminin immunohistochemistry. Laminin immunohistochemistry revealed marked vascular changes, including presumed neovascularization, in the lesioned striatum. Vessels with increased laminin immunoreactivity were demonstrated from 2 days up to at least 5 months following the injection. The majority was capillary vasculature, which was distributed throughout the lesioned striatum, sometimes being arranged densely along the needle tract. Fine spike-like sprouts called streamers were also loaded with laminin immunoreactivity. In contrast, laminin immunoreactivity in vessels in the control striatum was negligible. Vascular changes detected by laminin immunohistochemistry preceded but then almost paralleled gliosis demonstrated by glial fibrillary acidic protein immunohistochemistry. These results indicate that striatal injection of KA causes marked vascular changes including neovascularizations which are demonstrable by laminin immunohistochemistry.
The localization of monoamine oxidase (MAO) in nerve fibers associated with the major cerebral arteries in rats was studied using a new coupled peroxidation method modified by adding nickel ammonium sulfate at the electron microscopic level. MAO was, localized in some unmyelinated axons, both in the adventitia and in the periadventitial nerve bundles. Schwann cell cytoplasm encircling myelinated axons in the periadventitial nerve bundles also contained a MAO-reactive substance. The incidences of MAO-containing axons in the adventitial layer of the anterior cerebral, middle cerebral, internal carotid and basilar arteries were 32.3%, 29.5%, 29.6% and 21.1%, respectively. In the periadventitial nerve bundles, MAO activity was also demonstrated in 10.8% among unmyelinated axons. Preincubation with clorgyline, a specific inhibitor of MAOA, suppressed staining in the axons, both in adventitia and in periadventitial nerve bundles, but not in the Schwann cell cytoplasm. Conversely, preincubation with deprenyl, a specific inhibitor of MAOB, suppressed staining in the Schwann cell cytoplasm, but not in the axons. Therefore, MAO in the axons is regarded as MAOA and MAO in the Schwann cell cytoplasm as MAOB. In immunosympathectomized rats (anti-NGF-treated rats), MAO reactivity was suppressed in axons associated with cerebral arteries, but was retained in some Schwann cell cytoplasm. The results indicate that the MAO-containing unmyelinated axons coincide with the postganglionic noradrenergic ones. Thus, histochemical MAO staining may be utilized to study postganglionic sympathetic nerve fibers presumably innervating the major cerebral arteries at the electron microscopic level.
Neovascularization of the dissociated central nervous tissue transplanted into the lateral ventricle of the rat was studied using laminin immunohistochemistry. A very high immunoreactive response to laminin was demonstrated in the presumably newly formed vessels within the transplants and the graft-host borders. The growing tips and fine spike-like sprouts called 'streamers' were also highly stained with laminin immunoreactivity. In contrast, laminin immunoreactivity was negligible in the vessels in the host brain. Therefore, these results indicate that laminin may be utilized as a marker for the newly formed vessels in neural transplantations.
When WGA-HRP (wheat germ agglutinin-horseradish peroxidase conjugate) or HRP was injected into the regions around the superior central and/or the dorsal raphe nuclei in the cat, cell bodies of a number of non-pyramidal neurons were labeled in Ammon's horn. Thus the existence of direct projections from non-pyramidal neurons in Ammon's horn to the rostral raphe regions in the brainstem was suggested in the cat.
To elucidate the possible association of human T-lymphotropic virus type I (HTLV-I) and chronic neurological diseases, 156 serum samples from patients with various neurological diseases, including multiple sclerosis, chronic progressive myelopathy, chronic inflammatory polyradiculoneuropathy, myasthenia gravis, polymyositis, motor neuron disease, and tension headache, and healthy control subjects were examined for IgG antibodies to HTLV-I by three independent techniques--gelatin particle agglutination test, enzyme-linked immunosorbent assay, and Western blot assay. Specificity of antibodies was assessed by homologous competitive inhibition on Western blot assay. Six patients (3 with chronic progressive myelopathy, 1 with chronic inflammatory polyradiculoneuropathy, 1 with motor neuron disease, and 1 with tension headache) had high-titer HTLV-I antibodies. Twelve patients (5 with multiple sclerosis, 1 with chronic progressive myelopathy, 2 with chronic inflammatory polyradiculoneuropathy, 2 with myasthenia gravis, and 2 with motor neuron disease) had low-titer HTLV-I antibodies that reacted with a single gag protein, p19 or p24, on Western blot assay. In 4 (2 with multiple sclerosis, 1 with chronic progressive myelopathy, and 1 with chronic inflammatory polyradiculoneuropathy) of these 12, the antibodies that were all directed to p19 were determined to be specific by homologous competitive inhibition. In the remaining 8 patients (3 with multiple sclerosis, 1 with chronic inflammatory polyradiculoneuropathy, 2 with myasthenia gravis, and 2 with motor neuron disease), restricted reactions against p19 or p24 were considered to be nonspecific because they were not inhibited by homologous competitive inhibition. The results suggest that in some patients chronic myeloneuropathy diagnosed as chronic progressive multiple sclerosis, chronic progressive myelopathy, and chronic inflammatory polyradiculoneuropathy may be associated with HTLV-I or related retroviruses.
Successfully transplanted neurons and their sprouting processes were demonstrated by Phaseolus vulgaris leucoagglutinin (PHA) marking. PHA is transported anterogradely and readily reveals the post-transplantation growth of the neuronal processes. Suspensions of fetal central nervous tissue, prepared by dissociation of embryonic rat brain, were marked with PHA and then transplanted into the striatum of nonimmunosuppressed young adult rats. At various intervals thereafter (1 day, 2 days, 1 week, 2 weeks, 1 month, and 2 months), the animals were sacrificed for histological examination with PHA and tyrosine hydroxylase (TH) immunohistochemistry. Up to 2 weeks after transplantation, PHA immunohistochemistry was capable of demonstrating grafted neurons and their presumably regenerated neuronal processes. However, at periods 1 month or longer after transplantation, PHA immunohistochemistry was unreliable. Thus, the PHA marking method has limitations in terms of its retention period, when applied to the intracerebral transplantation of dissociated cell suspensions. Nevertheless, the method presented here can be utilized to study neuronal regeneration as well as the relationship between transplanted neurons and the host tissue.
Twenty patients with myasthenia gravis (MG) were studied prospectively for up to 5 years after thymectomy, in order to clarify the relationships between disease severity, anti-acetylcholine receptor antibody (anti-AChR) titres, proportions of circulating CD4+CD8+ cells (CD4+CD8+ cell level) and major lymphocyte subsets. The CD4+CD8+ cell levels were closely related to the clinical change within 1 year after surgery in 8 patients who showed a preoperative elevation in the cell levels. This group of patients consisted of six thymomatous and two non-thymomatous patients; the latter were both negative for anti-AChR. The anti-AChR titres generally changed in parallel with the clinical state in 9 of the 16 patients who were followed up for more than a year after thymectomy, and the CD4+CD8+ cell levels were useful in predicting the clinical course in 6 of the above 9 patients and 3 other patients, including antibody-negative cases. The present study suggests that the CD4+CD8+ cell levels may serve as an indicator for long-term prognosis of MG.
A 38-year-old man with severe canal stenosis at the level of the atlas is reported. The clinical manifestations were muscular weakness and wasting of the upper limbs and spastic paresis of the lower limbs, which all progressed slowly. The atlas was hypoplastic and its retrodental space was narrow. The spinal cord was markedly compressed between the odontoid process and the posterior arch of the atlas. The clinical manifestations improved after a posterior laminectomy of the atlas.
Erythrocyte membrane fluidity was examined by electron spin resonance spectra using nitroxide fatty acid spin labels in spinocerebellar degeneration (SCD). Subjects with SCD, motor neuron disease (MND) and controls did not differ in fluidity of the deep site (hydrophobic region) of the erythrocyte membrane. However, the fluidity of the shallow site (hydrophilic region) in the erythrocyte membrane was significantly less fluid in SCD than in controls and MND (outer hyperfine splitting of 5-nitroxide stearic acid: SCD 54.70 +/- 0.43 G, controls 53.57 +/- 0.41 G, MND 53.54 +/- 0.35 G, P less than 0.001). Serum HDL-cholesterol and membrane fluidity correlated significantly in controls, but not in SCD. A significant negative correlation between age and membrane fluidity was found in SCD, but not in controls. These data suggest that membrane abnormality exists in SCD and may be concerned with aging.
A 21-year-old female with mixed connective tissue disease (MCTD) experienced nausea, headache, consciousness disturbance, nuchal rigidity, and a temperature of 38.5 less than or equal to C three days after the intake of sulindac (300 mg/day). Cerebrospinal fluid analysis revealed an opening pressure of 310 mm of water, a predominantly lymphocytic pleocytosis, and elevated protein content of 89 mg/dl. After discontinuing sulindac, the aseptic meningitis improved in five days. In the acute stage, CT scan disclosed contrast enhancement in the cerebral hemispheres, which suggests that hypersensitivity may be involved in the pathogenesis of nonsteroidal antiinflammatory drug (NSAID) induced aseptic meningitis.