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Ag/Al₂O₃ catalysts with various Ag contents were characterized by thermal gravimetry (TG), differential thermal analysis (DTA), temperature-programmed desorption (TPD), NH₃ and CO₂ adsorption calorimetry, FT-IR spectroscopic method, and diffuse reflectance spectra (DRS). It was found that hydroxy groups on alumina have a close relationship with Ag loading either through ion-exchange with the proton of an acidic –OH or bonding with oxygen of a basic –OH species. An Ag loading of less than 240 μmol g^-1 decreases the Lewis acid sites but increases the Brønsted acid sites with medium NH₃ adsorption energy. A greater Ag loading induces interaction between NH₃ molecules and Ag oxides, leading to reduction of Ag oxides and dissociation of adsorbed NH₃. A large amount of Ag loading produces greatly enhanced basicity. The changes in the loaded form of silver on alumina are discussed. The appropriate acid–base property plays an important role in de-NO_x activity using propane as the reductant.

Two genetically distinct acid beta-galactosidases are apparently involved in the hydrolysis of galactosylceramide in fibroblasts. These beta-galactosidases were activated by different bile salts. The classical galactosylceramidase (galactosylceramidase I, EC 3.2.1.46) was activated by sodium taurocholate, while the other galactosylceramidase (galactosylceramidase II) was activated by sodium cholate. The former was genetically lacking in globoid cell leukodystrophy (GLD) and the latter in GM1 gangliosidosis. Galactosylceramidase II cross-reacted with antibody raised against purified GM1 ganglioside beta-galactosidase (EC 3.2.1.23) from the human placenta. The purified beta-galactosidase had galactosylceramidase II activity, which was competitively inhibited by GM1 ganglioside. Thus, galactosylceramidase II seems to be identical to GM1 ganglioside beta-galactosidase and lactosylceramidase II. Galactosylceramidase II had a very low affinity for galactosylsphingosine. In the galactosylceramide-loading tests using fibroblasts from patients with GLD and GM1 gangliosidosis, both cell lines hydrolyzed the incorporated galactosylceramide, with lower rates than control fibroblasts but higher than the fibroblasts from patients with I-cell disease, in which both galactosylceramidase I and II were deficient. These results indicate that galactosylceramide is hydrolyzed by two genetically distinct beta-galactosidases and explain well that galactosylsphingosine but not galactosylceramide accumulates in the brain of patients with GLD.

Identification of the localization of human T lymphotrophic virus type I (HTLV-I) proviral DNA in the central nervous system (CNS) is crucial to the understanding of the pathogenesis of HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) pathogenesis. We have developed a sensitive detection method, called two-step polymerase chain reaction (PCR) in situ hybridization, which enabled us to detect the HTLV-I proviral DNA in paraffin-embedded spinal cord tissue sections from HAM/TSP patients. HTLV-I proviral DNA was detected only in the nucleus of lymphocytes that had infiltrated into the spinal cord. However, no proviral DNA was amplified in any neuronal cells, including neurons and glial cells. This indicates that the demyelination of the spinal cord by HTLV-I as a result of viral infection of oligodendrocytes or neuronal cells is unlikely. The T cell receptor V beta gene sequence from lymphocytes in the spinal cord lesions taken from the same HAM/TSP autopsy cases revealed unique and restricted CDR3 motifs, CASSLXG(G) (one-letter amino acid. X is any amino acid), CASSPT(G), and CASSGRL which are similar to those described in T cells from brain lesions of multiple sclerosis (MS) and in a rat T cell clone derived from experimental allergic encephalomyelitis (EAE) lesions. The present results suggest that T cells containing restricted V beta CDR3 motifs, which are also found in MS and EAE, become activated upon HTLV-I infection and infiltrate into the spinal cord lesions of HAM/TSP patients.

Twelve patients with idiopathic painful ophthalmoplegia were studied by CT, which was found to be normal in 6 patients, but with a high density area in the orbit in the others. This abnormal high density area was not found when CT was performed at a relatively early stage of the disease, but was seen when it was performed more than 1 month after the onset of symptoms. Orbital phlebography was performed in 6 of 12 patients; 3 with normal and 3 with abnormal CT findings. An occlusion of the superior ophthalmic vein was seen in 3 patients with abnormal CT, but not in 3 patients with normal CT. All 12 patients improved with administration of corticosteroids. The results suggest that the intraorbital abnormality revealed by CT may be due to an inflammatory process in the chronic stage and/or the oedematous and infiltrating processes in soft tissues which can be caused by the occlusion of the superior ophthalmic vein or cavernous sinus.

Using high-performance liquid chromatography, adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN) were diagnosed by the analysis of fatty acids in sphingomyelin. The analytical method was simple, sensitive and accurate. In ALD and AMN patients, very long chain fatty acids (C26:0, C25:0 and C24:0 on the base of C22:0) were elevated not only in plasma and erythrocyte membranes but also in whole blood samples. An increase of long chain fatty acids was also shown in sphingomyelin of cultured skin fibroblasts. One heterozygote for ALD showed intermediate values between homozygotes and controls. Thus, high-performance liquid chromatography is a valuable method to detect increased long chain fatty acids for the diagnosis of ALD or AMN.

A case of adult type mucolipidosis with ß-galactosidase and sialidase deficiency is described. This patient, a woman aged 20, had mental retardation, macular cherry-red spots, corneal clouding, gargoyle-like face, cerebellar ataxia, myoclonus and convulsions beginning at the age of 14. Bony deformities, vacuoles in the peripheral lymphocyte and foamy cells in the bone marrow were also noted. Biopsy study of the sural nerve and vermiform appendix disclosed many vacuoles in almost every kind of cells, although the accumulated substance in these vacuoles could not be characterized histochemically or ultrastructurally. Deficient leukocyte ß-galactosidase and sialidase were confirmed. There was increased urinary sialoglycopeptide and increased siliac acid and hexosamine in the glycoprotein of lymphocytes. Leukocytes sialidase activities of the parents were 30 to 50% of the control values. These results suggest a genetic defect of sialidase.

Several forms of Alzheimer amyloid precursor protein (APP) mRNA are generated by alternative splicing. Among them, the APP695 mRNA skipping the exon 7 and 8 is expressed specifically in neurons, suggesting that this alternative splicing is regulated in a neuron-specific manner. As the first step for investigating the mechanism of the neuron-specific splicing, a mini-gene system was developed, in which mini-APP genes consisting of the exon 6, 7, 8, 9 and their flanking regions were introduced into neuronal and nonneuronal cultured cell lines to see their expression profiles. In the system the exon 7 and 8 of the mini-gene were significantly skipped in the neuronal cell, and the deletion study indicated that cis-acting elements for skipping the exons existed in the corresponding skipped-exon and its flanking regions. A small deletion upstream of the exon 8 suppressed the skipping of the exon 8 in the neuronal cell, suggesting that one of the regulatory sequence(s) for the exon skipping exists in a small region upstream of the skipped exon.

We found unstimulated (spontaneous) peripheral blood lymphocyte (PBL) proliferation significantly increased in 14 patients with human T-lymphotropic virus (HTLV)-I-associated myelopathy (HAM) compared with findings in HTLV-I seropositive non-HAM carriers (N 8) or HTLV-I seronegative controls (N 16). The proliferative response to phytohemagglutinin, concanavalin A, or pokeweed mitogen was decreased in the HAM patients. Cell clusters were frequent in cultures of unstimulated PBL from the HAM patients, but much less common in the controls or carriers. This spontaneous PBL proliferation was depressed when adherent-cell populations were depleted from the cultures. IL-2 activity increased in the supernatant of 3-day cultured cells from HAM patients, but not in cultured cells from the controls. Since IL-2 receptor positive cells increased in HAM, this spontaneous PBL proliferation is probably a response to IL-2 through the expression of IL-2 receptors.

We report on the clinical efficacy of a slow-release formulation of bromocriptine studied in a multi-center, double-blind trial using standard bromocriptine as the control. We randomly allocated enrolled patients (N 243) to either the slow-release or normal bromocriptine group. Sixty of them were de novo patients. The maintenance dose of slow-release bromocriptine was 14.2 ± 0.7 mg/d and that of standard bromocriptine 13.5 ± 0.7 mg/d (mean ± SE). The slow-release formulation was taken twice and the standard three times a day. Forty-one percent of the patients treated with the slow-release bromocriptine and 32 of the patients treated with the standard bromocriptine showed moderate or marked improvement in the global improvement rating. There were no serious side effects, and the frequency of vomiting and epigastric discomfort was lower in the patients treated with the slow-release bromocriptine. Clinical efficacies for tremor, rigidity, akinesia, and gait disturbance were comparable between the two drugs tested. The slow-release bromocriptine seems to be a valuable drug for the treatment of Parkinson's disease with less severe side effects than regular bromocriptine.

We studied the serum antibody titers to Epstein-Barr virus (EBV) in 11 patients with HTLV-I-associated myelopathy (HAM). HAM patients showed significant increases in IgG antibodies to EBV-capsid antigen (VCA) and -early antigen (EA) and in VCA-specific IgA compared with 25 seronegative subjects. However, there were no significant differences in antibodies to EBV-nuclear antigen (EBNA) or to other viruses between the two groups. In HAM patients, altered antibody responses occurred specifically to EBV-associated antigens, not to other viruses.

Influence of food on the serum concentration and kinetics ambenonium chloride (AMBC) has been examined in thirteen patients with myasthenia gravis (MG).

An 18-year-old boy showed childhood onset of mental retardation, neurogenic muscle atrophy with hyperreflexia, Marfan-like features, multiple epiphyseal dysplasia, increased urinary excretion of dermatan sulfate, and decreased lysosomal enzyme activities in ß-galactosidase, ß-glucuronidase, and N-acetyl-ß-d-glucosaminidase. This case may be a new syndrome, the combination of neurogenic muscle atrophy with lysosomal enzyme deficiencies.

A case is described with the characteristic clinical features of rigid spine syndrome: childhood onset in a male, very slowly progressive weakness and muscle atrophy, limitation of neck and trunk flexion, joint contractures, normal intelligence, no clear family history, increased serum CPK levels and myopathic patterns in EMG and muscle biopsy specimens. Myopathic patterns with various histological changes in muscle biopsy specimens were seen in all eight reported cases of the rigid spine syndrome, but there are no characteristic histological findings in the rigid spine syndrome.

An antibody against the synthetic C-terminal peptides deduced from the cDNA of the gene responsible for X-linked adrenoleukodystrophy (ALD) was produced to characterize the product of the ALD gene. The antibody reacted with the 80 kDa band protein in control fibroblasts, while no bands were detected in the fibroblasts from a patient with ALD (#163), in which mRNA of the ALD gene was undetectable based on Northern blot analysis. The 293T cells transfected with the full-coding cDNA inserted in the expression vector produced a new 80 kDa protein, as detected by Western blot. In an immunocytological study, the staining was in a punctate pattern, in the normal fibroblasts. However, there was no punctate staining in the #163 cells. These data thus indicate that the ALD gene encodes an 80 kDa membrane protein.Copyright 1994, 1999 Academic Press, Inc.

A low concentration of differentiation inducers such as dimethylsulphoxide (DMSO), sodium butyrate, hexamethylene bisacetamide and sodium phenylacetate greatly enhanced the antiproliferative effect in vitro and in vivo of interferon alpha (IFN-alpha) to several human lung adenocarcinoma cells. The agents induced morphological changes in the adenocarcinoma cells and the agents together with IFN-alpha-induced alkaline phosphatase activity, which is a typical marker of type II pneumocyte maturation. To understand the mechanism of the DMSO-enhanced interferon sensitivity, we examined the effect of DMSO on high-affinity IFN-alpha receptor and interferon-stimulated promoter-binding factors. The lung adenocarcinoma cells were not impaired in IFN-alpha receptor and interferon-stimulated gene transactivation factor 3 (ISGF-3). Our data suggest that the enhancement of interferon sensitivity in the lung adenocarcinoma cells acts downstream of the activation of ISGF-3.

Our two patients with lysinuric protein intolerance, a 14-year-old boy and his 12-year-old sister, showed growth retardation and their bone ages were retarded. Growth hormone secretion responded to glucagon-propranolol and showed a good response to arginine. However, growth hormone showed little response to insulin. After the oral administration of arginine hydrochloride, growth hormone showed a good response to insulin and glucagon-propranolol, and gain in height and weight accelerated. This result may suggest that an adequate supply of arginine is effective in improving the growth retardation in lysinuric protein intolerance.

In a case of cerebrotendinous xanthomatosis (CTX), confirmed biochemically and histologically, quantitative histological studies of the biopsied sural nerve revealed significantly higher incidence of de- and remyelination and onion bulb than in controls. The density of total myelinated fibers fell within the range of controls, although the density of large myelinated fibers seemed to be slightly decreased. It was suggested that the preferential involvement of the myelin sheath and Schwann cell may exist in CTX.

We report the first Japanese case of familial Creutzfeldt-Jakob disease (CJD) with the heterozygous point mutation at codon 200 of the prion protein gene. This suggests that the mutation is not race-specific. The clinical and pathologic features of this case are not different from those of sporadic CJD without point mutations. Some healthy members of the family also carry the same mutation in the autosomal dominant inheritance expression.

We studied subsets of peripheral blood lymphocytes (PBL) from 12 patients with human T-lymphotropic virus type I (HTLV-I) associated myelopathy (HAM). The percent of OKT8 cells was significantly decreased, and the percentages of OKDR cells and IL-2R cells and the ratio of OKT4 cells to OKT8 cells were significantly increased compared with either HTLV-I seronegative healthy adults (controls) or HTLV-I seropositive non-HAM subjects (carriers). The subsets of PBL from eight carriers showed no differences from those in controls. The patients with HAM showed significantly higher antibody titers to HTLV-I compared with carriers. These altered PBL subsets and high HTLV-I antibody titers in the patients suggest that immune functions are in an activated state in HAM.

Studies showed a significant decrease in the macrophage neutral protease and lymphocyte acid protease activities in patients with multiple sclerosis in remission, a significantly decreased neutral protease activity in macrophages in patients with myasthenia gravis and a significantly decreased acid protease activity in macrophages and lymphocytes in patients with polymyositis. No remarkable abnormalities were found in patients with myotonic dystrophy. These results suggest that multiple sclerosis, myasthenia gravis and polymyositis have an abnormality in immunological function.

A patient with adrenoleukodystrophy and his mother, a carrier, showed an elevated ratio of very long-chain fatty acids to long-chain fatty acids and decreased beta-galactosidase activity. Other lysosomal enzyme activities were normal except for the borderline level of arylsulfatase-A activity. However, the father and other patients with variant forms of adrenoleukodystrophy showed normal beta-galactosidase and other lysosomal enzyme activities.

Two siblings with congenital myopathy showing myasthenic manifestations together with congenital cataract are reported. Their muscle weakness fluctuated and was alleviated by edrophonium chloride. Their serum creatine kinase activity was elevated, and the waning phenomenon was observed on repetitive nerve stimulation. Biopsied muscle showed degenerative changes with type 1 fibre predominance and abnormal morphology of neuromuscular junctions.

A 37-year-old woman with scapulohumeral muscular atrophy, rigid spine and cardiopathy is reported. Muscle weakness, advanced atrioventricular block and contractures at the neck, elbows and ankles had occurred during her childhood. An autosomal dominant mode of inheritance was suggested because her mother, sister and brother had the same disorder. Pleomorphic mitochondria had accumulated in the subsarcolemmal space of the skeletal muscle. There was no evident enzyme defect in the mitochondrial electron transport system. Although the clinical features had some similarity with those of Emergy-Dreifuss muscular dystrophy or rigid spine syndrome, the pattern of inheritance and the muscle pathology differed.

In a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS] who had normal mitochondrial enzyme activity, high doses of coenzyme Q10 (CoQ) were administered. Clinical improvement with decreased serum lactate and pyruvate levels was observed. Though the mechanism of action of CoQ is not known, a trial is worthwhile in patients with MELAS.

A 25-year-old man with lung abscess and signs of an abscess in the rostral brain-stem was cured by large doses of antibiotics and stereotactic aspiration of the abscess.

A double-blind, multi-center study was performed on patients with HTLV-I-associated myelopathy (HAM) to evaluate the therapeutic effect of treatment with natural interferon-alpha (HLBI). Forty-eight HAM patients were enrolled and treated with either 0.3 MU (n equals 15), 1.0 MU (n equals 17), or 3.0 MU (n equals 16) of HLBI for 28 days. Clinical evaluation included motor dysfunction, urinary disturbances, and changes of neurologic signs. The frequency of therapeutic response judged as excellent to good 4 weeks after starting therapy and 4 weeks after completion of therapy were 7.1% (1 of 14) and 8.3% (1 of 12) in the 0.3-MU group, 23.5% (4 of 17) and 26.7% (4 of 15) for the 1.0-MU group, and 66.7% (10 of 15) and 61.5% (8 of 13) for the 3.0-MU group. The therapeutic benefit in the 3.0-MU group was significantly higher than in the 0.3-MU group. There was no significant difference in the incidence of symptomatic side effects between groups. Abnormal laboratory data were obtained for some patients in the 1.0-MU and 3.0-MU groups; however, the treatment schedule could be continued in most patients. These results suggest that HAM patients may be safely treated with HLBI 3.0 MU every day for 4 weeks with favorable clinical effects.