Glycosphingolipids of leukemic cells in adult T-cell leukemia-lymphoma.

We analyzed lipids from leukemic cells of two patients with adult T-cell leukemia and compared them with those from T-cell lymphocytes of normal subjects. The neutral glycosphingolipids and gangliosides which were isolated were characterized by thin-layer chromatography and neuraminidase treatment. Both leukemic cells and normal lymphocytes had monoglycosylceramide and diglycosylceramide as major neutral glycosphingolipids. In one patient, diglycosylceramide was markedly increased. II3NeuAc-LacCer (GM3) and more complex gangliosides were detected in both cells. The most characteristic finding in leukemic cells was the occurrence of a disialylated ganglioside, II3(NeuAc)2-LacCer (GD3), which is not found in normal lymphocytes and neutrophils. This ganglioside may be due to the induced synthesis in association with malignant transformation.

Minimal record of disability in multiple sclerosis--application to Japanese patients.

The Japanese version of Minimal Record of Disability in MS was applied to randomly selected Japanese MS cases in order to determine the applicability of the scales and also to get the general trends of the disabilities of Japanese MS. The scales did reflect impairment of functional systems, in which visual system was most severe. The average DSS was 4/10. Incapacity status or environment status were well correlated with impairment of pyramidal or bowel/bladder systems. They also correlated with DSS. Duration of the illness was correlated with the severity of impairment, disability or handicap. Accumulation of such a core data base may help in management of the MS problems in the world.

Meclofenoxate therapy in tardive dyskinesia: a preliminary report.

Tardive dyskinesia seems to occur as a result of diminished cholinergic and enhanced dopaminergic activity in the striatum. Meclofenoxate has been shown to increase cerebral cholinergic activity. To ameliorate the tardive dyskinesia, meclofenoxate was given orally, 600-1200 mg/day, for 6-12 weeks. The effects of the drug were evaluated by scoring the degree of involuntary movement. Among 11 subjects with tardive dyskinesia or dystonia, 4 improved markedly, 1 moderately, 2 slightly, and there was no improvement in 4. One patient with subacute oral dyskinesia, induced by administration of neuroleptics for 1 month, improved markedly. The possibility that meclofenoxate may be effective in dealing with dyskinesias that are induced by neuroleptics warrants further attention.

Clinical electrophysiologic studies of HTLV-I-associated myelopathy.

Six patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) were studied by electrophysiologic methods. Upper-limb short-latency somatosensory evoked potentials showed slight delay of the N9-N20 interpeak latency in one of 12 limbs, while the lower-limb short-latency somatosensory evoked potentials showed prolonged N20-P40 interpeak latency in eight of 12 limbs. Frequent polyphasic potentials and occasional giant spikes were observed in the distal extremities. F-wave conduction velocity was delayed in some patients. Results of the other nerve conduction studies were unremarkable. Our data provide a valuable extension of the clinical examination of HAM and offer encouragement for a more extensive electrophysiologic study of this entity, especially in the spinal cord.

Lymphocyte alpha-glucosidase in late-onset glycogenosis type II.

We describe the biochemical characterization of lymphocyte alpha-glucosidase in a 23-year-old man with intermediate clinical features between the childhood and adult forms of glycogenosis type II (Pompe's disease). Acid alpha-glucosidase activity was markedly reduced, but immunologic cross-reactive material against human liver acid alpha-glucosidase protein could be detected, and its amount was normal. In this patient, the disorder was induced by the catalytically inactive enzyme with a normal amount of enzyme protein.

The risk of development of HTLV-I-associated myelopathy/tropical spastic paraparesis among persons infected with HTLV-I.

Using data obtained in national surveys of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) conducted in Japan in 1987 and 1988, we estimated the yearly and lifetime risk that HAM/TSP will develop in an HTLV-I-infected person. "Definite" HAM/TSP was defined as slowly progressive myelopathy with antibodies to HTLV-I in both serum and cerebrospinal fluid. Estimates of HTLV-I infection rates in eight endemic prefectures, by age group and sex, were obtained from serologic studies of blood donors; population figures, by age group, sex, and prefecture, were obtained from the census. Of 589 definite cases of HAM/TSP reported nationally, 397 occurred in residents of the eight endemic prefectures; of these, 170 reported onset of illness during the years 1982-1988 (average incidence, 24.3 cases/year). Using the estimated HTLV-I infection rates and the 1985 census figures, we estimated the number of HTLV-I-infected persons in the eight prefectures in 1985 at 794,800. We therefore estimated the incidence of HAM/TSP among HTLV-I-infected persons at 3.1 x 10(-5) cases/year; assuming a lifetime of 75 years, the lifetime incidence is approximately one quarter of 1%. This estimate is important in counseling persons such as blood donors found to be infected with HTLV-I.

High CSF lactate and pyruvate content in Kearns-Sayre syndrome.

We studied lactate and pyruvate concentrations in CSF and blood of a patient with Kearns-Sayre syndrome (KSS), 3 patients with ocular myopathy and 11 normal control subjects. We found significant elevation of lactate and pyruvate in the CSF of the patient with KSS, suggesting a disorder of CNS lactate-pyruvate metabolism.

Nationwide survey of multiple sclerosis in Japan. Clinical analysis of 1,084 cases.

Between October 1972 and October 1973, the first nationwide survey of the multiple sclerosis group of diseases in Japan was performed by the Multiple Sclerosis Research Committee of Japan, supported by the Japan Ministry of Health and Welfare. Reports on 1,084 patients with the multiple sclerosis group were collected: 509 patients with multiple sclerosis, 82 with Devic's disease, 357 with "multiple sclerosis possible," and 136 with "other or unclassified demyelinating diseases." The natural history in the present nationwide series of multiple sclerosis patients showed considerable similarity to that of patients in Western countries, suggesting that multiple sclerosis in Japan is essentially the same as that in the Western countries. However, the previously reported special characteristics of Japanese multiple sclerosis patients, namely, a higher rate of visual impairment at onset, a higher rate of optic nerve involvement during the course of illness, and a higher rate of Devic's disease, were reconfirmed in the present series.

Mitochondrial encephalomyopathy with lactate-pyruvate elevation and brain infarctions.

We studied a patient with somatic growth failure with easy fatigability, myopathy with mitochondrial abnormality, increased lactate and pyruvate in blood and CSF, mental retardation, seizure, myoclonus, deafness, cerebellar ataxia, and blindness with macular degeneration and optic atrophy. Pathologic findings included multiple brain infarctions and massive calcification in the basal ganglia. Biochemical studies of isolated mitochondria revealed decreased oxygen consumption in skeletal muscle, diaphragm, and brain, suggesting an abnormality in the respiratory chain.

The Crow-Fukase syndrome: a study of 102 cases in Japan.

Clinical manifestations of 102 cases with the Crow- Fukase syndrome (the syndrome of polyneuropathy, anasarca, skin changes, endocrinopathy, dysglobulinemia, and organomegaly), with or without myeloma, were reviewed. Fifty-six cases with myeloma consisted of 31 with osteosclerotic, 17 with mixed osteosclerotic and osteolytic, and 8 with osteolytic. Forty-six cases without myeloma consisted of 2 with extramedullary plasmacytoma, 33 with M protein alone, and 11 with polyclonal protein alone. There was no significant difference in incidence of the major clinical manifestations between the two groups with and without myeloma. They had a common characteristic histologic finding of the lymph node resembling that of Castleman's disease.

Function of Ca2+ in phosphatidylcholine-hydrolyzing phospholipase D activation in osteoblast-like cells.

We investigated the function of Ca2+ in the activation of phosphatidylcholine (PC)-hydrolyzing phospholipase D (PLD) in osteoblast-like MC3T3-E1 cells. Fetal calf serum (FCS) stimulated the formation of choline in a dose-dependent manner in the range between 0.6% and 10%. The effect of a combination of FCS and 12-O-tetradecanoylphorbol-13-acetate, a protein kinase C (PKC) activator, on the formation of choline was additive. Staurosporine, an inhibitor of protein kinases, enhanced the formation of choline induced by FCS. BAPTA/AM, a chelator of intracellular Ca2+, inhibited the formation of choline induced by FCS. The depletion of extracellular Ca2+ by EGTA markedly reduced the FCS-induced formation of choline. SK&F 96365, an inhibitor of receptor-operated Ca2+ entry, significantly inhibited the choline formation induced by FCS. On the other hand, nifedipine, an inhibitor of L-type voltage-dependent Ca2+ channels, had little effect on the choline formation. TMB-8, an inhibitor of Ca2+ mobilization from intracellular Ca2+ store, significantly inhibited FCS-induced choline formation. These results strongly suggest that Ca2+ mobilization, through both the influx via receptor-operated Ca2+ channel and the release from intracellular Ca2+ store, plays an important role in the activation of PLD in osteoblast-like cells.

Acquired anhaptoglobinemia in panhypopituitarism.

This report describes the first case of acquired anhaptoglobinemia observed in panhypopituitarism (Sheehan's syndrome). Anhaptoglobinemia was completely reversed by the administration of hydrocortisone. These findings suggest that haptoglobin synthesis and/or secretion are modulated by hydrocortisone.

Immunological studies of HTLV-I associated myelopathy.

We report the immunological studies of 50 cases with a chronic progressive myelopathy associated with elevated antibodies to human T-cell lymphotropic virus type I (HTLV-I) and adult T-cell leukemia-like cells (HAM). These are as follows: (1) T-cell activation; (2) increase of the OKT4/OKT8 ratio, due mostly to increased inducer/helper T cells and/or decreased suppressor/cytotoxic T cells; (3) decrease of natural killer cell numbers and activity; and (4) increase of immunoglobulins (IgG, IgA). Our results provide evidence that autoimmune events may participate in the pathogenesis of HAM and may be relevant in the hypothesis of common immune mechanisms between HAM and HTLV-I positive tropical spastic paraparesis.

Thrombomodulin as a marker for vascular tumors. Comparative study with factor VIII and Ulex europaeus I lectin.

Thrombomodulin (TM) is a newly described endothelial cell-associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. Various vascular tumors were characterized with immunoperoxidase staining with the use of a polyclonal anti-TM serum. The staining patterns of TM were compared with those of Factor VIII-related antigen (FVIII-RAG) and Ulex europaeus agglutinin-I (UEA-I), which have been used as markers for endothelial cells. The results showed that TM is a specific and a highly sensitive marker for angiosarcomas in comparison with FVIII-RAG or UEA-I. In contrast, UEA-I is more sensitive for benign vascular tumors than TM or FVIII-RAG. The other mesenchymal tumors of nonvascular origin showed negative staining for three endothelial markers. These results indicate that TM is a new specific and sensitive tool for the diagnosis of angiosarcomas.

Neutral oligosaccharides in the urine of a patient with glycogen storage disease type II.

Neutral oligosaccharides were isolated from urine of an adult patient with glycogen storage disease type II, a deficiency of lysosomal acid alpha-glucosidase, by chromatography on columns of activated charcoal, Dowex 50 X 2 and Dowex 1 X 2. Total neutral oligosaccharides in the urine of the patient were increased about 5-fold as compared with those in normal controls. The most accumulated oligosaccharide was separated by Bio-Gel P-2 column chromatography, and finally purified by paper chromatography. Based on various studies, including carbohydrate analysis, chemical ionization mass spectrometry, fast atom bombardment mass spectrometry, degradation by glucoamylase and isopullulanase, and methylation analysis, the structure of this oligosaccharide was deduced to be Glc alpha 1----6Glc alpha 1----4Glc alpha 1----4Glc. This oligosaccharide appears to be accumulated in urine of the patient with acid alpha-glucosidase deficiency as an end product of the hydrolysis of glycogen.

Two positional isomers of sialylheptasaccharides isolated from the urine of a patient with sialidosis.

We describe the structures of two positional isomers of sialylheptasaccharide isolated from the urine of a patient with sialidosis with partial deficiency of beta-galactosidase. Based on structural studies including compositional sugar analysis, exoglycosidase digestion, chemical ionization mass spectrometry, proton nuclear magnetic resonance spectrometry, and methylation analysis, their structures were deduced to be as follows: AcNeu alpha 2----6Gal beta 1----4GlcNac beta 1----2Man alpha 1----3(Man alpha 1----6)Man beta 1----4GlcNac; AcNeu alpha 2----6Gal beta 1----4GlcNac beta 1----2Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNac. Sialyloligosaccharide 1 has previously been found in the urine and liver of patients with mucolipidosis I and II and sialidosis, but sialyloligosaccharide 2 has not been found yet in human urine. These two sialyloligosaccharides could not be completely separated by any chromatographic procedures tested. The analytical techniques, including methylation study and NMR spectroscopy, could not clearly detect the differences between them. However, alpha-mannosidase treatment gave important information for the structural analyses of these sialyloligosaccharides.

Pharmacokinetic study of aniracetam in elderly patients with cerebrovascular disease.

The clinical pharmacokinetics of the cognitive enhancer, aniracetam (200 mg), was studied in elderly patients with cerebrovascular disease (CVD) and compared with those of young healthy volunteers. Six female hospitalized patients (mean age 84.5 years) were used in this study. The serum level of anisic acid and p-methoxyhippuric acid, major metabolites of aniracetam, reached a peak at 2 h after oral administration, and returned to basal level by 6 h. Mean creatinine clearance was 20-30 ml/min. The t1/2 of metabolites was increased by 4- to 7-fold in the elderly patients compared with young volunteers. This study showed that tmax, t1/2, and AUC were enlarged in the elderly; however, no clinical side effects were observed.

Schwartz-Jampel syndrome associated with von Willebrand's disease.

We report a very rare case of Schwartz-Jampel syndrome associated with von Willebrand's disease. This association might be coincidental because of the different modes of inheritance of the two disorders. However, we speculate that there might be some link between the two disorders, for example in the locus of the affected gene.

Pain-related somatosensory evoked potentials in dementia.

Pain-related somatosensory evoked potentials (pain SEPs) were examined in 25 demented and non-demented patients to investigate the cognitive function for pain in the progression of dementia. Pain SEPs by CO2 laser stimulation were recorded together with auditory event-related potentials (auditory ERPs). P340 in pain SEPs and P300 in auditory ERPs were analysed. The latency of P300 evoked in mildly demented patients was inversely correlated with the Mini-Mental state examination score, and the latency of P340 was also inversely correlated to that score but to a lesser extent. Pain SEPs were not recorded in 4 of 7 severely demented patients. These results indicate that the P340 component of pain SEPs is apparently different from the P300 component of auditory ERPs and suggest that the pain perception in severely demented patients may be abnormal.

A case of nemaline myopathy with ophthalmoplegia and mitochondrial abnormalities.

A case of nemaline myopathy with ophthalmoplegia is reported. The patient was a 35-year-old man born of consanguineous parents. He had a myopathic face, high-arched palate, nasal voice, scoliosis, very thin trunk and marked muscle weakness involving face, neck, limbs and trunk. He also had ptotis of the left eyelid and mild bilateral ophthalmoplegia, also detected by electrooculogram. Biopsy of gastrocnemius muscle revealed nemaline rods. At the ultrastructural level, the rods appeared to have axial and cross striations, and in cross-sections at high magnification they seemed to have a crystal lattice structure. Intranuclear rods were also observed. In addition to the rods, abnormal mitochondria including a number of paracrystalline inclusions were seen.