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Biomedical subjects

K Fujihara

Publications and source records attributed to K Fujihara.

At least 19 recordsLinked to original sources

Optic-spinal form of multiple sclerosis and anti-thyroid autoantibodies.

The optic-spinal form of multiple sclerosis (OSMS), characterized by recurrent involvement of optic nerve and spinal cord with rare brain magnetic resonance imaging lesions, is relatively common among Asians. While individual cases of OSMS with anti-thyroid autoantibodies (ATABs) have been reported, the frequency of ATAbs in OSMS and classical multiple sclerosis has not been studied. We studied serum ATAbs and anti-nuclear antibodies (ANA) in 46 Japanese patients with multiple sclerosis: 14 with OSMS, and 32 with non-OSMS. Six patients were positive for ATAbs: five women with OSMS and one man with non-OSMS. The frequency of ATAbs in OSMS (5/14) was significantly higher than that in non-OSMS (1/32; P = 0.007), but the frequency of ANA did not differ between OSMS (3/14) and non-OSMS (6/32; P = 0.99). There may be a pathogenetic link between anti-thyroid autoimmunity and a subgroup of OSMS in Japanese.

Adult

Leber's hereditary optic neuropathy mitochondrial DNA mutations in familial multiple sclerosis.

Leber's hereditary optic neuropathy (LHON) can be difficult to distinguish from optic neuritis due to multiple sclerosis (MS). For several decades an association of LHON and MS has been suspected, and within the past 7 years the LHON nucleotide (nt)-3460 and nt-11778 mtDNA mutations have been identified in several patients with MS-like phenotypes. To further study this association, we tested 42 index patients with clinically definite, familial MS for the LHON mtDNA mutations at nt-3460, nt-11778, and nt-14484. No patients had a pathogenic LHON mtDNA mutation; however, two MS patients with unilateral optic neuritis harbored the nt-15257 mtDNA polymorphism that was reported originally as a pathogenic LHON mutation. Several investigators have shown evidence that the nt-15257 mtDNA mutation is not primarily pathogenic. Therefore, we conclude that pathogenic LHON mtDNA mutations are absent or rare in unselected patients with familial, clinically definite MS (95% confidence intervals for each of the negative mutations 0-7.0%).

Adult

Alteration of neurotensin receptors in MPTP-treated mice.

We examined the sequential changes in neurotensin receptors in the striatum and substantia nigra of mouse brains lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by receptor autoradiography, in comparison with the alterations in dopamine uptake sites. The mice received four intraperitoneal injections of MPTP (10 mg/kg) at 1-h intervals and then the brains were analyzed at 6 h and 1, 3, 7, and 21 days after the treatments. [3H]Neurotensin and [3H]mazindol were used to label neurotensin receptors and dopamine uptake sites, respectively. [3H]Neurotensin binding was significantly decreased in the striatum from 6 h to 21 days after MPTP treatment. In the substantia nigra, pars reticulata also showed a significant decrease in [3H]neurotensin binding from 3 to 21 days post-MPTP treatment. However, no significant change in [3H]neurotensin binding was observed in the pars compacta even after 21 days. On the other hand, [3H]mazindol binding was markedly decreased in the striatum and substantia nigra from 6 h to 21 days after MPTP treatment. These results indicate that neurotoxin MPTP can produce a severe decrease in neurotensin receptors and dopamine uptake sites in the striatum and substantia nigra of mice. Thus, our findings provide evidence that the dysfunction in neurotensin receptors may be involved in the degenerative processes causing Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Increases in [3H]FK-506 and [3H]L-N(G)-nitro-arginine binding in the rat brain after nigrostriatal dopaminergic denervation.

Receptor autoradiographic technique was studied to investigate sequential changes in FK-506 binding proteins, nitric oxide synthase and dopamine uptake sites in the brain 1 week to 8 weeks after unilateral 6-hydroxydopamine injection of the medial forebrain bundle in rats. [3H]FK-506, [3H]L-N(G)-nitro-arginine and [3H]mazindol were used to label FK-506 binding proteins (immunophilin), nitric oxide synthase and dopamine uptake sites, respectively. [3H]FK-506 binding showed about 13-25% increase in the ipsilateral striatum from 2 to 8 weeks after degeneration of nigrostriatal pathway. However, no significant change in [3H]FK-506 binding was observed in the ipsilateral substantia nigra during the postlesion periods. In the contralateral side, [3H]FK-506 binding also showed about 13-25% increase in the striatum from 2 to 8 weeks postlesion. The substantia nigra showed a 21% increase in [3H]FK-506 binding only 2 weeks after the lesioning. On the other hand, [3H]L-N(G)-nitro-arginine binding showed about 21-31% increase in the parietal cortex and striatum 1 week or 2 weeks postlesion. In the contralateral side, a 21% increase in [3H]L-N(G)-nitro-arginine binding was found in the dorsolateral striatum only 1 week postlesion. In contrast, degeneration of nigrostriatal pathway caused a conspicuous loss of [3H]mazindol binding in the ipsilateral striatum (87-96%), substantia nigra (36-73%) and ventral tegmental area (91-100%) during the postlesion periods. In the contralateral side, no significant changes in [3H]mazindol binding were observed in these areas up to 8 weeks after the postlesion. The present study demonstrates that unilateral injection of 6-hydroxydopamine into the medial forebrain bundle of rats can cause a significant increase in [3H]FK-506 and [3H]L-N(G)-nitro-arginine bindings in the brains. In contrast, a marked reduction in [3H]mazindol binding is observed in the brains after the lesioning, indicating severe damage to nigrostriatal dopaminergic pathway. These results suggest that immunophilin and nitric oxide synthase may play some role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease.

Animals

Clinical and MRI study of brain stem and cerebellar involvement in Japanese patients with multiple sclerosis.

OBJECTIVES: To investigate the clinical and MRI features of brain stem and cerebellar lesions in Japanese patients with multiple sclerosis. METHODS: A retrospective study of 66 consecutive Japanese patients with multiple sclerosis (42 women and 24 men) was done by reviewing the medical records and MRI films. Forty nine patients were diagnosed as having clinically definite multiple sclerosis and 17 patients as having clinically probable multiple sclerosis according to Poser's criteria. Prevalence rates of each brain stem and cerebellar manifestation and frequency and distribution of MRI lesions in these patients were studied. RESULTS: Forty three patients (65%) had one or more infratentorial manifestations. Cranial nerves were clinically involved in 28 patients (42%), and most of the lesions were identified by MRI. Among them, manifestations of facial, trigeminal, and abducens nerves were relatively common. Cerebellar ataxia was found in 20 patients (30%). The MRI study showed that the lesions responsible for ataxia in these patients were mainly found in the cerebellar peduncles, but cerebellar hemispheric lesions were detected in only four patients (6.4%). CONCLUSION: The low frequency (6.4%) of the cerebellar MRI lesions in these patients is in sharp contrast with the figures reported for white patients with multiple sclerosis (50%-90%). Racial and genetic differences may have an influence on the susceptibility of each part of the CNS to demyelination in multiple sclerosis.

Asian People

Human parvovirus B19 infection in multiple sclerosis.

The association of human parvovirus B19 (PVB19) infection with the development of several systemic autoimmune diseases has been confirmed in other studies. To determine if there is any association of PVB19 infection with multiple sclerosis (MS), we studied the prevalence of serum anti-PVB19 IgG and IgM by an enzyme-linked immunosorbent assay and PVB19-specific DNA in the cerebrospinal fluid (CSF) by the polymerase chain reaction method in a total of 46 patients during exacerbation or remission of MS. Anti-PVB19 IgG was detected in 65.8% of the patients' sera. The percentage was significantly higher than that in age-matched healthy control subjects (40%; p = 0.019), but was not higher in patients with other neurological diseases (50%; p = 0.16). There was no correlation between serum anti-PVB19 IgG status and antinuclear antibodies or oligoclonal IgG bands in CSF. Serum anti-PVB19 IgM and PVB19 DNA in CSF were consistently negative in the patients during exacerbation of MS. Although MS patients may be commonly infected with PVB19, our results suggest that there is no active PVB19 infection during exacerbation of MS.

Adolescent

Decrease in multiple sclerosis with acute transverse myelitis in Japan.

Acute transverse myelitis (ATM) may be a manifestation of multiple sclerosis (MS) and was reported to be more common among Japanese MS patients than in Caucasian MS patients. Recently there are arguments whether clinical manifestations of MS may have changed. Therefore, we studied the frequency of ATM in MS and the clinical subtypes of MS in 86 clinically definite MS patients whose onsets were in 1970-1979, 1980-1989, and 1990-1998 in Sendai City, Japan. Fifty-six of the patients were women and 30 were men. Forty-four patients had the conventional form of MS (C-MS) commonly seen in Western countries, and 42 had optic-spinal or spinal forms of MS (OSS-MS). Twenty MS patients had ATM, and all of them were belong to optic-spinal form of MS. ATM was not seen in any cases of C-MS. The mean onset age (years) of the clinical subtypes was 25.5 in C-MS, 34.1 in OSS-MS without ATM, and 30.9 in OSS-MS with ATM. Among the patients whose onset of the disease was in 1970-1979, 60.0% of them were cases of OSS-MS with ATM, but such cases were markedly decreased to 5.3% in 1990-1998. In contrast, the frequency of C-MS increased to 63.2% in 1990-1998 compared with 20.0% in 1970-1979. Analysis of the data by the year of birth of the patients showed similar results. Our data suggest that the frequency of ATM in MS markedly decreased, and that of C-MS increased during the last 30 years in Sendai, Japan. Since the genetic background of Japanese has not changed, some exogenous factors, such as food, infectious microorganisms, and chemicals in our environment, may be responsible for the change.

Adult

[Steroid-responsive diffuse cerebral white matter lesions in a case of intractable fungal meningoencephalitis].

We report a case of fungal meningoencephalitis with steroid-responsive diffuse cerebral white matter lesions. A 49-year-old male developed auditory hallucination, confusion and fever, on April, 1994. He was diagnosed as having cryptococcal meningoencephalitis based on the detection of cryptococcal antigens in the cerebrospinal fluid (CSF). Intravenous administration of fluconazole resulted in improvement of his neurologic symptoms and CSF findings. For the next seven months, he was treated with oral fluconazole and the neurological status was stable. However, soon after the dose of fluconazole was tapered, he became confused and febrile, which made him admitted to our hospital. Neurological examination on admission showed disturbance of consciousness, disorientation and meningeal irritation. The CSF examination revealed mild pleocytosis (mostly lymphocytes), elevated protein and normal glucose levels, although fungus was not detected. The T2-weighted image of brain MRI demonstrated diffuse hyperintense lesions in the bilateral cerebral white matters. GD-DTPA enhanced MRI showed spotty enhanced lesions in the periventricular white matters. The neurologic symptoms were once relieved after intravenous administration of fluconazole was started, but two months later, he became comatose and needed ventilatory support, despite amphotericine B therapy. Then, a needle brain biopsy targeting the white matter lesion was done. Histopathology of the specimen showed chronic inflammation with granuloma formation and T lymphycyte infiltrate around the small vessels, though fungus was not detected in the tissue. Combined therapy with corticosteroid and antifungal agents remarkably improved the neurological symptoms as well as the MRI findings. In the present case, fungal infection possibly induced an altered immune reactions which resulted in the steroid responsive diffuse cerebral white matter lesions.

Anti-Inflammatory Agents

[Pathogenetic significance of HTLV-I infection and immune surveillance in HAM].

HTLV-I proviral DNA load is significantly increased in HTLV-I associated myelopathy (HAM) compared with asymptomatic HTLV-I seropositive carriers (SPC), and this spread of HTLV-I infection seems to be critically important in the pathogenesis of HAM. Thus, in this report, cellular immune surveillance against HTLV-I was reviewed. (1) MHC class I-restricted cytotoxic T lymphocytes (CTL) activities are detected in peripheral blood mononuclear cells (PBMC) of HAM. CTL release various proinflammatory and cytotoxic cytokines, chemokines, and proteases. Since CTL are also found in the spinal lesions of HAM, CTL may contribute to the tissue damage. In spontaneous proliferation of PBMC in HAM, CD 4/CD 8 is decreased due to the proliferation of CD 8 + CTL. CD 4/CD 8 is inversely correlated with the clinical severity of HAM. Collectively, CTL may be involved in the pathogenesis of HAM. (2) Activity and subsets of natural killer (NK) cells are lower in HTLV-I-seropositive individuals. Moreover, NK have only a weak cytotoxicity against HTLV-I infected cells. (3) Antibody-dependent cell-mediated cytotoxicity (ADCC) are impaired in HAM compared with SPC due to the suppressed effector cell activity. Since ADCC effectively lyse HTLV-I infected cells in vitro, the impaired ADCC may in part allow the spread of HTLV-I infection in HAM, and potentiation of ADCC may have an anti-HTLV-I therapeutic effect.

Antibody-Dependent Cell Cytotoxicity

The effects of 4-aminopyridine on motor evoked potentials in multiple sclerosis.

In order to study the effects of 4-aminopyridine (4-AP) on impulse conduction in multiple sclerosis (MS), we studied motor-evoked potentials (MEPs) in the upper (U/E) and lower extremities (L/E) of six MS patients with stable spastic paraparesis before and after intravenous administration of 4-AP. As a result, we found a significant increase in mean amplitudes in U/E and L/E (P = 0.008) and a significant decrease in the variability of onset latencies in L/E (P = 0.017) without any significant changes in mean and shortest onset latencies. In four limbs of three patients in whom there were no detectable MEP responses before 4-AP administration, definite responses were elicited after 4-AP administration. 4-AP seems to have its therapeutic effects by improving impulse conductivity in demyelinated nerve fibers or by enhancing central or peripheral synaptic transmission, which thus results in coordinated contractions of more muscle fibers in MS.

4-Aminopyridine

Clinical and laboratory features of myelitis patients with anti-neutrophil cytoplasmic antibodies.

Although perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) are associated with vasculitic neuropathy, their association with central nervous system (CNS) disorders has not been studied except for one report on optic-spinal type of multiple sclerosis associated with serum pANCA. We examined pANCA in sera from 98 patients with various CNS disorders, such as 58 MS, 17 myelitis, 12 HTLV-1 associated myelopathy, and 11 other CNS diseases using indirect immunofluorescence methods. The results showed serum pANCA to be positive in five patients with a peculiar type of myelitis, including two with MS and three with etiology unknown myelitis. All of these ANCA-positive patients were women and had acute or subacute myelopathy with various severities. MRI revealed segmental swelling of the spinal cord with T2 hyperintensity in the acute stage of the disease. Marked pleocytosis (227.8+/-101/mm3) and elevated protein level (128.8+/-52 mg/dl) in CSF were noted. Four of the patients had anti-nuclear antibodies and two had previous histories of symptoms suggesting autoimmune disorders. In a search for target antigens of pANCA, myeloperoxidase reactivity was found in the sera from two myelitis patients. Clinical and laboratory features of myelitis patients with pANCA in the present study are different from those of typical MS patients. Further study will be needed to delineate the role of pANCA in the pathogenesis of a specific type of myelitis.

Adolescent

Amplification of JC virus regulatory DNA sequences from cerebrospinal fluid: diagnostic value for progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease in the central nervous system caused by a ubiquitous human polyomavirus designated as JC virus (JCV). PML affects individuals with decreased immune competence and is now one of the common opportunistic infections in patients with AIDS. JCV DNAs in the brain of PML patients contain various PML-type regulatory regions that were generated from the archetypal regulatory region during persistence. Recently, many studies have suggested that detection of JCV DNA from the cerebrospinal fluid (CSF) may offer a tool for diagnosing PML. However, in all of these studies, coding sequences within the T antigen or capsid protein gene have been targeted for amplification. To amplify the JCV regulatory region, we established a nested PCR that could efficiently amplify the regulatory region from most JCV subtypes prevalent in the world. Using this PCR, we amplified JCV regulatory regions from the CSF samples from 4 patients strongly suspected of PML, whereas amplification was negative from 80 CSF samples from patients without PML. Sequencing of the amplified fragments revealed that they had unique deletions and/or duplications. Furthermore, in 3 PML patients, we analyzed the structures of regulatory regions derived from the brain as well as CSF. In each of these cases, the major regulatory sequence of both origins were identical. This finding indicates that JCV DNA in brain lesions is excreted in the CSF. Since the structures of PML-type JCV regulatory regions are unique to individual patients, the current PCR, if the amplified fragments are sequenced, can eliminate false positives that may arise from contaminations.

Brain

Complement activation as a cause of transient hypotension during plasmapheresis.

Hypotension is one of the most common adverse effect of plasmapheresis (PP) and often is attributed to hypovolemia due to extracorporeal circulation and the vasovagal reflex. Complements are activated during PP, and the activated complements are strong anaphylatoxins and potent vasodilators. Therefore, we studied the relationship between the transient hypotension and the plasma levels of activated complements during and after PP in 8 sessions of 7 patients using the Plasmafro OP-08 as a plasma separator. Five of the patients underwent immunoadsorption PP using the IM-TR 350 or IM-PH 350 as the adsorption column. The other underwent double filtration PP using the Evaflux 4A as a second filter. In 4 of 8 sessions, patients experienced transient hypotension with significantly elevated plasma levels of activated complements C3a and C5a. In contrast, patients without hypotension showed no increases in C3a and C5a values during PP. In this report, we emphasize the critical role of activated complements for hypotension during PP.

Adolescent

Progressive multifocal leukoencephalopathy in a patient with acquired immunodeficiency syndrome (AIDS) manifesting Gerstmann's syndrome.

We reported a case of acquired immunodeficiency syndrome (AIDS) via multiple blood transfusions, who manifested progressive multifocal leukoencephalopathy (PML) about 18 months after the development of AIDS. PML initiated with right hemiparesis, dysphasia, and Gerstmann's syndrome and resulted in death within 2 months after the onset. Neuroimaging examinations revealed white matter lesions mainly in the left posterior parietal lobe. The cortical gray matter also showed abnormal signal intensity. Peripheral CD4+ lymphocyte count was 81/microl. Routine cerebrospinal fluid (CSF) examinations were negative. CSF antibodies against herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus as well as serum antibody against toxoplasma gondii were negative. Though autopsy or biopsy of the brain was not performed, JC virus genomes were detected in the CSF sample by a polymerase chain reaction, and their sequencing showed unique alterations of the regulatory regions, characteristic to PML-type JC virus.

Acquired Immunodeficiency Syndrome

Novel compound tetra-, dinucleotide microsatellite polymorphism in the tumor necrosis factor/lymphotoxin locus.

A polymorphic (TGCG)n, tetranucleotide repeat was discovered juxtaposed to the (GT)n dinucleotide repeat that comprises the tumor necrosis factor a microsatellite (TNF) located telomeric to the tumor necrosis factor/lymphotoxin gene cluster. The degree of complexity of this compound tetra-,dinucleotide microsatellite consists of 16 potential alleles of combined length ranging from 24 to 54 bp. The pattern of frequencies of individual alleles belonging to the compound TNFa microsatellite was established from 52 healthy volunteers and was found to be highly heterogeneous. The data diverges significantly from previously published statistics that recognized only a simple variable dinucleotide tandem repeat. The newly recognized compound tetra-, dinucleotide TNFa microsatellite polymorphism establishes a more accurate genetic basis to explore potential linkage with disease susceptibility genes located within this region of the class III major histocompatibility complex. In addition, variable tumor necrosis factor and lymphotoxin production may reflect the more complex polymorphic nature of this microsatellite region. Finally, compound microsatellites probably exist elsewhere, throughout the human genome. Recognition of their presence may have a considerable impact on the validity of past and future microsatellite-based genetic analyses.

Base Sequence

[A juvenile case of Lambert-Eaton myasthenic syndrome with severe emaciation].

Most of the patients with Lambert-Eaton myasthenic syndrome (LEMS) are over 40 years of age at onset and have a malignant neoplasm, especially pulmonary small cell carcinoma. Juvenile cases of LEMS are rare and have not been reported in Japan. We report a 21-year-old women whose onset of LEMS was at 17 years of age. In the early stage of the disease, she had limb muscle weakness and was diagnosed has having seronegative myasthenia gravis (MG) based on decrementing response in low frequency repetitive nerve stimulation, positive edrophonium test, and negative serum anti-acetylcholin receptor antibodies. Serum anti-voltage-dependent-calcium-channel (VGCC) antibody was negative with an available assay system. She was thymectomized and received anti-cholinesterases, corticosteroids, and cyclophosphamide, but their therapeutic effects were not evident. Two years later, she was confined to bed due to sever emaciation (Her body weight reduced from 47 Kg to 27 Kg.), bulbar palsy, and limb muscle weakness. She needed respiratory support and tube feeding. Type II fiber atrophy, which is non-specific, but is a common finding in LEMS, was seen in the biopsied muscle of the patient. On the other hand, postsynaptic folds and clefts of all seven motor end-plates in the specimen were normal, which is against the diagnosis of MG. Recently, she was found to have anti-VGCC antibody with an improved assay system. Despite vigorous examination, no malignancy or other autoimmune disorders have been found. 3,4-Diaminopyridine was effective to improve limb muscle powers, but she is still bedridden.

Adult

[A case of multiple intracranial tuberculoma diagnosed by open brain biopsy].

To provide histological diagnoses of brain diseases, CT-guided stereotactic brain biopsy (CT-SBB) has been widely used because of its less invasive technique compared with open brain biopsy (OBB). However, CT-SBB is not always diagnostic. We report a case of multiple intracranial tuberculoma whose diagnosis was not made by CT-SBB but by OBB. The patient is a 46-year-old man with insulin-dependent diabetes mellitus who had been receiving immunosuppressive agents (azathioprine, cyclosporin, and prednisolone) after renal transplantation for diabetic renal failure for 9 years. He gradually developed febrile, headache and unsteady gait. Brain MRI demonstrated multiple intracranial lesions involving left fronto-temporal and right parietal lobes, left cerebellar hemisphere, and the fourth ventricle. Although the MRI findings were consistent with those of previously reported cases of intracranial tuberculoma, other conditions, such as malignant lymphoma and toxoplasmosis, were not ruled out. Therefore, CT-SBB targeting the left temporal lobe lesion was done for definitive diagnosis, but it revealed only mild perivascular infiltration of mononuclear cells and hemorrhage. He was transferred to our clinic for further evaluation. On examination, mild truncal and limb ataxia on the left were noted in addition to the neurological findings corresponding to diabetic retinopathy and neuropathy. Despite vigorous laboratory examinations, including repeated bacterial cultures and PCR of cerebrospinal fluid, no evidence of tuberculous infection was obtained. A tentative diagnosis of multiple intracranial tuberculoma was made, and anti-tuberculous drugs (isoniazid 400 mg, ethambutol 750 mg, and pyrazinamide 1.5 g) were administered. Since his symptoms deteriorated because of ventricular dilatation resulting from the enlarged lesion in the fourth ventricle after a temporary clinical improvement, VP-shunting and OBB from the left temporal lobe lesion were done. The excised lesion was firmly encapsulated and the histological examination revealed typical pathology of tuberculoma. Ziehl-Neelsen staining and PCR for Mycobacterium tuberculosis of the biopsied specimen were also positive. Further administration of increased doses of anti-tuberculous drugs (isoniazid 600 mg, ethambutol 500 mg, pyrazinamide 2.0 g and intramuscular injection of streptomycin 0.3 g twice a week) eventually ameliorated the symptoms and shrank the lesions. In case of intracranial tuberculoma, the needle of CT-SBB may not penetrate the firm capsule of tuberculoma and only the surrounding brain tissue may be obtained as in the present case. Therefore, it is recommended to consider OBB from the beginning for definitive diagnosis of intracranial tuberculoma. Paradoxical worsening of the clinical and laboratory findings of tuberculosis in spite of appropriate anti-tuberculous therapy as seen in the present case has been described in both pulmonary and extra-pulmonary tuberculosis. The phenomenon, called transient worsening, could happen and we have to keep it in mind during the treatment of intracerebral tuberculoma.

Antitubercular Agents

Antibody-dependent cell-mediated cytotoxicity (ADCC) in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP)

Defects in immune surveillance mechanisms may allow increased replication of human T-lymphotropic virus type I (HTLV-I) in peripheral blood mononuclear cells in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). To explore this possibility, antibody-dependent cell-mediated cytotoxicity (ADCC) against HTLV-I infected cells in HAM/TSP and in asymptomatic HTLV-I-seropositive carriers (SPC), was studied. ADCC activity was significantly depressed in HAM/TSP compared to SPC subjects (p < 0.025) and was due to specific reduction in ADCC effector activity. On the other hand, there was no difference in antibody component of anti-HTLV-I ADCC (ADCC-Ab) activities between HAM/TSP and SPC, although patients with more severe forms of disease tended to have higher anti-HTLV-I ADCC-Ab activity. In HAM/TSP, depressed ADCC activity against HTLV-I due to reduced ADCC-effector activity may allow increased replication of HTLV-I which may implicate the development of inflammatory neuropathologic lesions of HAM/TSP.

Adult