Human histocompatibility leukocyte antigen (HLA) haplotype frequencies estimated from the data on HLA class I, II, and III antigens in 111 Japanese narcoleptics.

Matsuki, Kazumasa; Juji, Takeo; Tokunaga, Katsushi; Naohara, Tohru; Satake, Masahiro; Honda, Yoshiyuki

doi:10.1172/jci112211

Cited by 55 publications

(25 citation statements)

References 13 publications

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“…Only two other diseases, narcolepsy, associated with the HLA-DR2 allele (13), and celiac disease associated with the DQw2 allele (14), show such a strong association with the HLA-D region. In view of these results, we asked whether the DR4 and DRw6 alleles in PV patients were distinct from alleles in healthy individuals, and, by applying molecular biological approaches, whether it would be possible to obtain RFLPs that could discriminate PV patients from healthy individuals.…”

Section: Resultsmentioning

confidence: 99%

Detection of disease-specific restriction fragment length polymorphisms in pemphigus vulgaris linked to the DQw1 and DQw3 alleles of the HLA-D region.

Szafer¹,

Brautbar²,

Tzfoni³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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Pemphigus vulgaris in Israeli Ashkenazi and non-Ashkenazi Jews and in Austrian non-Jewish patients is strongly associated with the DR4 and DRw6 alleles of the HLA-D region class II genes. Restriction fragment length polymorphism analysis was undertaken with DQ.3, DQoa, and DRP cDNA probes. Hybridization with the DQB probe identifies Pvu II, BamHI, and EcoRV fragments that absolutely discriminate pemphigus vulgaris patients from healthy DR-, DQ-, and ethnic-matched controls. In contrast the DQa and DRB probes failed to identify disease-specific restriction fragment length polymorphism fragments. These studies indicate that DQwl and DQw3 polymorphisms carried by pemphigus vulgaris patients may be directly involved in predisposition to the disease or may be tightly linked to the susceptibility gene itself. To our knowledge, this is the first example of an HLA restriction fragment length polymorphism that is highly associated with susceptibility to autoimmune disease.Pemphigus vulgaris (PV) is a dermatological autoimmune disease mediated by autoantibodies directed against an antigen, intracellular cement substance, in the basement membrane of keratinocytes, resulting in blister formation (1, 2). This disease can be reproduced in monkeys or in mice after transfer of antibodies from PV patients (1, 2). Susceptibility to PV is strongly associated with serologically defined gene products of the HLA-D region (3, 4). technique. HLA-DR and -DQ typing was done on T-celldepleted B-cell-enriched lymphocytes by extended incubation cytotoxicity testing (7). The HLA antisera included alloantisera from the third Asia-Oceania Histocompatibility Workshop and sera of local origin.DNA Extraction, Digestion, and Binding to Nylon Membranes. Genomic DNA was extracted from peripheral leukocytes. After lysis of the erythrocytes, the leukocytes were treated with proteinase K at 0.2 mg/ml (Boehringer Mannheim) for 12 hr at 42°C. Two phenol/chloroform-isoamyl alcohol, 3:1 (vol/vol), and two isoamyl alcohol/chloroform, 1:24 (vol/vol), extractions followed. Thereafter, the DNA was precipitated with two volumes of absolute ethanol. After precipitation and several washes with ethanol, the DNA was dissolved in TE (1 mM Tris HCl/0.1 mM EDTA, pH 7.5) to give a final concentration of 1 mg/ml. Ten micrograms of each DNA sample was digested with 10 units of the following restriction enzymes: BamHI, Dra I, EcoRI, EcoRV, HincII, HindIII, Pst I, Pvu II, and Taq I. Digestion was carried out for 15 hr, and the DNA samples were subjected to electrophoresis at 30 V in agarose gel (0.7% agarose in Tris acetate buffer, pH 6.4, containing ethidium bromide at 20 ,ug/ml) for 36 hr. Gels were then transferred to Hybond N membranes (Amersham) as described by Southern (8).cDNA Probes and Hybridization. The DQa cDNA probe was furnished by Charles Auffray (College de France). The DQ,3 and DR8 cDNA probes were furnished by Hugh McDevitt and John Bell (Stanford University). Full descriptions of the probes appear elsewhere (9, 10). The probes were labeled by t...

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Section: Resultsmentioning

confidence: 99%

Detection of disease-specific restriction fragment length polymorphisms in pemphigus vulgaris linked to the DQw1 and DQw3 alleles of the HLA-D region.

Szafer¹,

Brautbar²,

Tzfoni³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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“…Serological HLA typing was performed by the modified two-stage complement-dependent microcytotoxicity method as described previously (18). The typing sera were obtained at Blood Transfusion Service, Tokyo University Hospital, or through serum exchange.…”

Section: Methodsmentioning

confidence: 99%

“…Both dominant and recessive modes of inheritance were evaluated for each model. For the first model, expected genotype frequencies under the dominant inheritance were calculated by the moment method as described by Thomson (23) and those under the recessive inheritance were calculated by the counting method of maximum likelihood as described previously ( 18). For the second model, the expected frequencies were computed according to the maximum likelihood method (23).…”

Section: Methodsmentioning

confidence: 99%

HLA antigens in Japanese patients with myasthenia gravis.

Matsuki

Juji²,

Tokunaga³

et al. 1990

J. Clin. Invest.

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“…As part of the characterization of our narcoleptic subjects we performed histocompatibility leukocycle antigen (HLA) typing. Seropositivity for HLA DRw15 and DQw6 in Caucasians and Orientals, or seropositivity for HLA DQw6 in African Americans is strongly (but not invariably) associated with narcolepsy (7,(23)(24)(25). Subject 3N was atypical from the other narcoleptics only in that she carried the DR4 antigen rather than the DRw15 antigen.…”

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confidence: 94%

Treatment of Narcolepsy with Methamphetamine

Mitler

Erman

1993

Sleep

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SummaryEight pairs of subjects (each consisting of a narcoleptic and a control matched on the basis of age, sex, educational background and job) were evaluated under the following double-blind, randomized treatment conditions: baseline, placebo, low dose and high dose methamphetamine. Subjects were drug-free for 2 weeks prior to beginning the protocol. Methamphetamine was the only drug taken during the protocol and was given in a single morning dose of 0, 20 or 40-60 mg to narcoleptics and 0, 5 or 10 mg to controls. The protocol was 28 days long, with each of the four treatment conditions lasting 4 days followed by 3 days of washout. Nighttime polysomnography and daytime testing were done during the last 24 hours of each treatment condition. Daytime sleep tendency was assessed with the multiple sleep latency test (MSLT). Daytime performance was assessed with performance tests including a simple, computer-based driving task. Narcoleptics' mean MSLT sleep latency increased from 4.3 minutes on placebo to 9.3 minutes on high dose, compared with an increase from 10.4 to 17.1 minutes for controls. Narcoleptics' error rate on the driving task decreased from 2.53% on placebo to 0.33% on high dose, compared with a decrease from 0.22% to 0.16% for controls. The effects of methamphetamine on nocturnal sleep were generally dose-dependent and affected sleep continuity and rapid eye movement (REM) sleep. Elimination half life was estimated to be between 15.9 and 22.0 hours. Mild side effects emerged in a dose-dependent fashion and most often involved the central nervous system and gastrointestinal tract. We concluded that methamphetamine caused a dose-dependent decrease in daytime sleep tendency and improvement in performance in both narcoleptics and controls. Methamphetamine at doses of 40-60 mg allowed narcoleptics to function at levels comparable to those of unmedicated controls. KeywordsNarcolepsy; CNS stimulants; Methamphetamine; MSLT; Polysomnography; Driving task Narcolepsy is a neurological disorder affecting some 250,000-350,000 individuals in the United States, a prevalence rate similar to that for multiple sclerosis (1-4). Narcolepsy is thought to stem from genetic or early developmental abnormalities in catecholamine regulation within the brain (5,6). The disorder is characterized by a pentad of symptoms: daytime somnolence, cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed nocturnal sleep (7,8). The etiology of daytime somnolence in narcolepsy is poorly understood, but seems to stem from dysregulation of the sleep/wake cycle, rather than from an excessive need for sleep (9,10). Hypnagogic hallucinations, sleep paralysis and cataplexy are manifestations of an underlying dysfunction in the control and organization of rapid eye movement (REM) sleep (7). Pathological somnolence is by far the most disabling and potentially dangerous symptom of narcolepsy. Pathological somnolence, whether from narcolepsy or from other causes such Note: This article was planned for the April issue, which included artic...

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Human histocompatibility leukocyte antigen (HLA) haplotype frequencies estimated from the data on HLA class I, II, and III antigens in 111 Japanese narcoleptics.

Cited by 55 publications

References 13 publications

Detection of disease-specific restriction fragment length polymorphisms in pemphigus vulgaris linked to the DQw1 and DQw3 alleles of the HLA-D region.

Detection of disease-specific restriction fragment length polymorphisms in pemphigus vulgaris linked to the DQw1 and DQw3 alleles of the HLA-D region.

HLA antigens in Japanese patients with myasthenia gravis.

Treatment of Narcolepsy with Methamphetamine

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