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Biomedical subjects

K Tokunaga

Publications and source records attributed to K Tokunaga.

At least 37 records · Page 2Linked to original sources
PubMed2003

Variations of human killer cell lectin-like receptors: common occurrence of NKG2-C deletion in the general population.

CD94 and NKG2 are members of the NK cell receptor families, and are encoded in the natural killer gene complex (NKC) on human chromosome 12p12-13, one of the candidate chromosomal regions for rheumatic diseases. To examine a possible association between variations in CD94 and NKG2 genes and genetic susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), we carried out a systematic polymorphism screening of NKG2-A (KLRC1), NKG2-C (KLRC2) and CD94 (KLRD1) genes on a population basis. In NKG2-A, previously considered to be highly conserved, 10 polymorphisms in the noncoding region and introns, as well as one rare variation leading to an amino acid substitution within the transmembrane region, c.238T>A (Cys80Ser), were detected. In NKG2-C, in addition to the previously described two nonsynonymous substitutions, c.5G>A (Ser2Asn) and c.305C>T (Ser102Phe), two polymorphisms were newly detected in the noncoding region. In CD94, only one single nucleotide substitution was identified in the 5' untranslated region. When the patients and healthy individuals were genotyped for these variations, no significant association was observed. However, although statistically not significant, NKG2-A c.238T>A (Cys80Ser) was observed in three patients with RA, but in none of the healthy individuals and the patients with SLE. Unexpectedly, in the process of polymorphism screening, we identified homozygous deletion of NKG2-C in approximately 4.3% of healthy donors; under the assumption of Hardy-Weinberg equilibrium, the allele frequency of NKG2-C deletion was estimated to be 20.7%. These results demonstrated that, although human NKG2-A, -C and CD94 are generally conserved with respect to amino acid sequences, NKG2-A is polymorphic in the noncoding region, and that the number of genes encoded in the human NKC is variable among individuals, as previously shown for the leukocyte receptor complex (LRC), HLA and Fcgamma receptor (FCGR) regions.

Adult↗
PubMed2003

A single-nucleotide substitution from C to T at position -1055 in the IL-13 promoter is associated with protection from severe malaria in Thailand.

We examined a possible association of single-nucleotide polymorphisms (SNPs) in the promoters of IL-3, IL-4, and IL-13 genes on the 5q31-33, IL-3 -16T>C, IL-4 -590T>C, and IL-13 -1055C>T, with severity of malaria in 361 adult malaria patients in Thailand. The IL-13 -1055T allele showed a significant association with protection from severe malaria (OR 0.51, 95% CI 0.32-0.80; P=0.0032 by the chi(2) test), while allele frequencies of IL-3 -16T>C and IL-4 -590T>C were not statistically different between mild and severe malaria patients. An IL-13 -1055C>T has been reported to alter the regulation of IL-13 production. Thus, IL-13 -1055T may show resistance to severe malaria through the alteration of IL-13 production.

Adolescent↗
PubMed2003

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing.

Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10(4)-10(8) PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. beta-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.

Adenoviridae↗
PubMed2002

Is the rupture of cerebral berry aneurysms influenced by the perianeurysmal environment?

PURPOSE: To evaluate contact between cerebral berry aneurysms and the perianeurysmal environment and to study the influence this contact has on aneurysm rupture. MATERIALS AND METHODS: In a series of 76 consecutive patients, pre- and post-contrast CT images of 87 aneurysms were evaluated. Aneurysm locations were identified and aneurysms were divided into two different groups depending on whether they had ruptured or not. Contact between aneurysms and the perianeurysmal environment was studied when present, and considered to be balanced or unbalanced according to symmetry of contact and type of contact interface, i.e. with bone, dura, etc. RESULTS: Rupture occurred in 47 aneurysms at an average maximum dome size of 7.4 mm. There was contact with elements of the perianeurysmal environment in 38 (81%) of ruptured cases and no evidence of contact in 7 (15%). The nature of contact was unclear in 2 (4%) ruptured aneurysms. In the aneurysms with contact, the nature of contact was unbalanced in 34 (72%) and balanced in 4 (9%). Unbalanced aneurysms ruptured at significantly smaller sizes (average: 7.7 mm) than balanced aneurysms (average: 11.4 mm). Seven aneurysms of small size (3.3-6.9 mm, average: 4.8 mm) were found to have ruptured, despite the fact that they were too small to exhibit contact with the perianeurysmal environment. In 40 unruptured aneurysms (average size: 6.3 mm), contact with the perianeurysmal environment was found in 15 aneurysms, for which balanced contact was found in 11 (27.5%) and unbalanced contact in 4 (10%), and no contact in 25 (62.5%). The average size of the aneurysms without contact (3.7 mm) was significantly smaller than that with balanced contact (10.3 mm) or with unbalanced contact (11.3 mm). CONCLUSION: Aneurysms exhibit contact with their perianeurysmal environment as soon as they reach a size that exceeds their allowance given by the local subarachnoid space. The contact with the environment was found to be an additional determinant parameter in the evolution of cerebral berry aneurysms and their risk to rupture.

Adult↗
PubMed2002

Performance of long J-shaped coils in large and giant intracranial aneurysms: an in vitro study.

We evaluated the performance of long straight coils (Detach-18 J-shaped coils) in large and giant in-vitro aneurysms. The coils consisted of a distal semicircular part 7 or 15 mm in diameter and a proximal 70 cm straight part having three types of stiffness: soft, standard, and stiff. We first investigated the ease of passage through a microcatheter in a realistic cerebral vessel model. Second, we made silicone models simulating lateral-type aneurysms of various spherical dome diameters (12, 15, 20 and 30 mm) and neck sizes (3-10 mm; dome-to-neck ratio approximately 3:1) and connected them to a pulsating circulatory pump. We evaluated the anchoring and folding patterns of the coils, stability of the microcatheter and coils in the aneurysm, and smoothness of delivery and retrieval of coils. Third, we compared the conformability of a coil in a large, irregular aneurysm with that of a spiral coil. The long J-shaped coils were easily advanced and retrieved through a microcatheter in a tortuous vessel model. In 12 mm spherical aneurysms, each coil made a complex framework, and knot formation or damage to the coil during withdrawal was often observed. In 15 mm aneurysms, the coils were all easily delivered and retrieved; standard-stiffness coils adapted best to this size. In 20 mm aneurysms, frameworks were less complex but still good with a standard or stiff coil, but those with soft coil were unstable and changed significantly within 3 min of detachment due to gravity and pulsatile flow. In 30 mm aneurysms, soft coils filled only the lower part during introduction, whereas a stiff coil still made a favourable framework. Conformability of a long J-shaped coil was superior to that of a spiral coil in a large, irregular aneurysm. Long J-shaped coils conform well to various configurations of large and giant aneurysms and can shorten procedures since a larger implant volume can be delivered with a single coil. Their principle of action may promote more favourable occlusion of irregular and large aneurysms by improved conformability and stability.

Embolization, Therapeutic↗
PubMed2002

The expected power of genome-wide linkage disequilibrium testing using single nucleotide polymorphism markers for detecting a low-frequency disease variant.

The expected power of genome-wide linkage disequilibrium (LD) testing for a low-frequency disease variant was examined using a simple genetic model in which the degree of LD between the disease variant and the adjacent single nucleotide polymorphism (SNP) marker decreases in proportion to the number of generations since the LD-generating event. In this study, the frequency of the SNP marker being in complete LD with a low-frequency disease variant at the LD-generating event was regarded as the random variable having the probability distribution expected from the neutral infinite sites model, which enables us to derive the formula for calculating the expected power of genome-wide LD testing without determining the allele frequency of the associated SNP marker. Such a treatment is essential for the evaluation of the power of LD testing, because the frequency of the associated marker allele is always unknown. The main results obtained are as follows: (1) genome-wide LD testing with a case-control design could identify a disease variant with a high penetrance, while a low-frequency disease variant showing a low penetrance is difficult to detect; (2) although the degree of LD increases as the number of markers increases, the power of LD testing does not necessarily increase after the significance level is adjusted by the Sidák correction or the Bonferroni correction based on the number of testings; (3) the use of SNP markers with only high-frequency minor alleles is more powerful for detecting LD even with a low-frequency disease variant than the use of SNP markers with both high- and low-frequency minor alleles. Thus, the study design of LD testing must be evaluated prior to the investigation. The present study will provide a guideline for determining the number of SNP markers and the range of SNP allele frequencies suitable for genome-wide LD testing.

Gene Frequency↗
PubMed2002

Association of HLA-DRB1*1502-DQB1*0501 haplotype with susceptibility to systemic lupus erythematosus in Thais.

In this study, we investigated the association of HLA-DRB1 and DQB1 with Thai patients with SLE. A highly significant increase in the frequency of DRB1*1502 and DQB1*0501 was found in SLE patients compared with normal controls. DRB1*1501 and DRB1*1602 were also slightly increased. In contrast, DRB1*1202 and DQB1*0301 were decreased, and DRB1*0406 and DRB1*1401 were not found in the patients' group. The haplotype analysis revealed that DRB1*1502 - DQB1*0501 was most strongly associated with SLE, and also suggested a primary role for DRB1 rather than DQB1. Taken together with the previous report which demonstrated the association of the same haplotype in Taiwan, our present observations strongly suggested that DRB1*1502 - DQB1*0501 is the major HLA haplotype that confers susceptibility to SLE in the South-east Asian populations.

Alleles↗
PubMed2002

HLA class II allele and haplotype frequencies in Koreans based on 107 families.

We have investigated the distribution of HLA class II alleles and haplotypes in 107 Korean families (207 parents and 291 children) for the HLA-DRB1, DRB3/B4/B5, DQA1, DQB1 and DPB1 loci. Numbers of alleles observed for each locus were DRB1: 25, DQA1: 14, DQB1: 15, and DPB1: 13. Only two to three alleles were observed for the DRB3 (*0101, *0202, *0301), DRB4 (*0103, * 0103102 N), and DRB5 (*0101, *0102) loci. These alleles showed strong associations with DRB1 alleles: DRB3*0101 with DRB1*1201, *1301 and *1403; DRB3*0301 with DRB1*1202 and *1302; DRB3*0202 with DRB1*0301, *1101, *1401 and *1405; DRB5*0101 and *0102 were exclusively associated with DRB1*1501 and *1502, respectively. The seven most common DRB1-DQB1 haplotypes of frequencies > 0.06 accounted for 52% of the total haplotypes. These haplotypes were exclusively related with the seven most common DRB1-DRB3/B4/B5-DQA1-DQB1 haplotypes: DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 (0.085), DRB1*0405-DRB4*0103-DQA1*0303-DQB1*0401 (0.082), DRB1*09012-DRB4*0103-DQA1*0302-DQB1*03032 (0.082), DRB1*0101-DQA1*0101-DQB1*0501 (0.075), DRB1*0701-DRB4*0103-DQA1*0201-DQB1*0202 (0.065), DRB1*0803-DQA1*0103-DQB1*0601 (0.065), and DRB1*1302-DRB3*0301-DQA1*0102-DQB1*0604 (0.065). When these haplotypes were extended to the DPB1 locus, much diversification of haplotypes was observed and only one haplotype remained with a frequency of > 0.06: DRB1*0405-DRB4*0103-DQA1*0303-DQB1*0401-DPB1*0501 (0.062). Such diversification would have resulted from cumulated events of recombination within the HLA class II region, and the actual recombination rate observed between the HLA-DQB1 and DPB1 loci was 2.3% (10/438 informative meioses, including 2 recombinants informative by analysis of TAP genes). Comparison of the distribution of DRB1-DQB1 haplotypes with other populations revealed that Koreans are closest to Japanese people. However, Koreans share a few haplotypes with white people and Africans, which are rare in Japanese: DRB1*0701-DQB1*0202 and DRB1*1302-DQB1*0609. The results obtained in this study will provide useful information for anthropology, organ transplantation and disease association studies.

Alleles↗
PubMed2002

Association of HLA-A*3303-B*4403-DRB1*1302 haplotype, but not of TNFA promoter and NKp30 polymorphism, with postherpetic neuralgia (PHN) in the Japanese population.

Herpes zoster is a common disease caused by reactivation of the varicella zoster virus (VZV). In a small number of herpes zoster patients, pain persists beyond 4 weeks or more after healing of vesicular eruptions; this condition is termed postherpetic neuralgia (PHN). Positive associations of human histocompatibility leukocyte antigens (HLA) class I antigens, A33 and B44, with PHN in the Japanese population have been reported. Our hypothesis is that susceptibility genes to PHN might exist in the HLA region and the study objective is to further examine possible associations of genes in HLA class I, II and III regions, HLA-A, -B, -DRB1, tumor necrosis factor alpha (TNFA) promoter, and a natural killer cell activating receptor, NKp30 polymorphisms with PHN. Although TNFA or NKp30 in the class III region had been considered as a candidate locus, we found no associations of TNFA promoter or NKp30 polymorphisms with PHN in this study. We demonstrated that HLA-A*3303, -B*4403 and -DRB1*1302 alleles were significantly associated with PHN (P = 0.0007 for A*3303, P = 0.001 for B*4403 and P = 0.001 for DRB1*1302). The frequency of the HLA-A*3303-B*4403-DRB1*1302 haplotype was also significantly higher in the PHN patients than in the healthy controls (P = 0.0039). Our results suggest that this haplotype might be related to the pathogenesis of PHN.

Adult↗
PubMed2002

Polymorphisms of human CD19 gene: possible association with susceptibility to systemic lupus erythematosus in Japanese.

CD19 regulates the signaling for B lymphocyte development, activation and proliferation. In mice, CD19 deficiency and overexpression were shown to result in hypogammaglobulinemia and autoantibody production, respectively. In the present study, we screened for the polymorphisms of CD19, and examined the detected polymorphisms for the association with rheumatoid arthritis (RA), Crohn's disease and systemic lupus erythematosus (SLE). Two SNPs, c.705G>T (P235P and IVS14-30C>T, were decreased (P = 0.0096 and P = 0.028, respectively), in SLE. A GT repeat polymorphism, c.*132(GT)(12-18), was detected within the 3'-untranslated region, and individuals with > or =15 times repeat was significantly increased in the independent two groups of Japanese SLE patients (P = 0.011 and P = 0.035, respectively); the overall difference between total SLE and controls was striking (P = 0.0061). No association was observed for RA and Crohn's disease. In addition, no variations other than the common polymorphisms were detected in four patients with common variable immunodeficiency, the phenotype of which resembles CD19 deficient mice. In Caucasian SLE families, this GT repeat polymorphism was rare. CD19 mRNA level in the isolated peripheral blood B lymphocytes was lower in individuals possessing (GT)(15-18) alleles compared with those without these alleles, both in controls and in SLE patients; however, the difference did not reach statistical significance. These results suggested that either the slight reduction in the CD19 mRNA level associated with the elongation of GT repeat, or an allele of another locus in linkage disequilibrium with CD19 (GT)(15-18), may be associated with susceptibility to SLE in Japanese.

3' Untranslated Regions↗
PubMed2002

Studies on the association of Fc gamma receptor IIA, IIB, IIIA and IIIB polymorphisms with rheumatoid arthritis in the Japanese: evidence for a genetic interaction between HLA-DRB1 and FCGR3A.

We recently detected a new single nucleotide polymorphism of FcgammaRIIB gene, which alters an amino acid within the transmembrane domain from Ile to Thr (I232T), and its association with SLE in the Japanese. This study was performed to examine whether FCGR2B-I232T was associated with susceptibility to rheumatoid arthritis in the Japanese. At the same time, FCGR2A, 3A and 3B polymorphisms were also examined. Genotyping of FCGR2B-I232T, FCGR2A-H131R, FCGR3A-F176V and FCGR3B-NA1/2 polymorphisms were performed using genomic DNA. Association with RA was analyzed in 382 Japanese patients with RA and 303 healthy individuals using a case-control approach. In addition, the same groups of patients and controls were genotyped for HLA-DRB1 to examine possible interaction with FCGR genes. Significantly different distribution of genotype, allele carrier and allele frequencies was not observed between patients with RA and healthy individuals in any of the four polymorphisms. When the subjects were stratified according to the carriage of HLA-DRB1 shared epitope (SE), significant increase of FCGR3A-176F/F genotype was observed in SE positive patients compared with SE positive healthy individuals (P=0.009, P(corr)=0.07). In conclusion, FCGR3A-176F/F genotype was considered to confer risk through genetic interaction with HLA-DRB1 SE.

Adult↗
PubMed2002

Analysis on the association of human BLYS (BAFF, TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis.

Recent studies indicated a substantial role of BLyS (BAFF, TNFSF13B) in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in humans and in animal models. This study was conducted to screen for polymorphisms of human BLYS, and to examine whether they are involved in the genetic susceptibility to human SLE and RA. A systematic polymorphism screening was performed in the coding region, 5' and 3' untranslated regions, and promoter region of human BLYS. Association of the detected polymorphisms with SLE and RA was analyzed in 221 Japanese patients with RA, 156 with SLE, and 227 healthy individuals, using the case-control approach. Four single nucleotide polymorphisms (SNPs) in the promoter, one SNP in intron 1, and one rare nonsynonymous substitution (Ala105Thr) in the coding region were detected. The BLYS SNPs were found to form three common haplotypes. Significant association with the susceptibility to SLE or RA was not observed. However, a tendency for the increase of -871T/T genotype was observed in SLE patients with anti-Sm antibody (P=0.082). BLYS mRNA level was significantly elevated in the monocytes from individuals carrying -871T (P=0.010). In addition, although statistically not significant, 105Thr allele was slightly increased in patients with RA compared with controls (P=0.058). Characterizing the functional and clinical significance of these new SNPs requires further study.

Adult↗
PubMed2002

Polymorphisms of tumour necrosis factors A and B in breast cancer.

We assayed for germline single nucleotide polymorphisms (SNPs) in the TNFB and TNFA genes in patients with breast cancer. SNPs were observed in the first intron of TNFB (G/A) and at -1031 (T/C), -863 (C/A), -857 (C/T) and -308 (G/A) in the promoter region of TNFA from peripheral leucocytes in 95 breast cancer patients and 190 healthy subjects as controls. The TNFB*G/TNFB*G homozygote (23.2% vs. 5.8%, P= 0.001) was predominant in patients, while the TNFB*A/TNFB*A homozygote was less frequent in patients (34.7% vs. 46.3%, P = 0.041) than in the control subjects. Breast cancer was not associated with SNPs in the TNFA promoters. Although the TNFB SNP failed to associate with any clinicopathological parameter of breast cancer, a substantial difference in pathology among tumour stages for the -857 SNP in TNFA was detected. These results indicate that TNFB has both tumorigenic and antitumorigenic capabilities depending on the genotype: the TNFB SNP TNFB*G/TNFB*G genotype gave an increased risk for breast cancer and that of TNFB*A/TNFB*A gave resistance to breast cancer (OR = 5.3395%; CI: 2.33-12.19). The results suggest that the TNFB*G allele plays some role in the tumorigenesis or activation of dormant tumour cells, but the TNFB*A allele induces some function(s) leading to the inhibition of tumorigenesis.

Adult↗
PubMed2001

Gene expression analysis in human monocytes, monocyte-derived dendritic cells, and alpha-galactosylceramide-pulsed monocyte-derived dendritic cells.

In vitro proliferation and functional activation of V alpha 24NKT cells following stimulation with alpha-galactosylceramide (alpha-GalCer)-pulsed dendritic cells (DCs) have been observed. Because little is known about the molecular events on DCs following interaction with alpha-GalCer, we performed gene expression profiling of 2400 genes in monocytes and monocyte-derived immature DCs pulsed with alpha-GalCer (alpha-GalCer-imDCs). Overall, the expression levels of 48 genes were up-regulated and 28 were down-regulated in alpha-GalCer-imDCs. Semiquantitative RT-PCR analysis on monocytes, imDCs, alpha-GalCer-imDCs, and mature DCs confirmed the up- and down-regulation of the mRNA expression levels of 28 selected genes. Notably, we identified the specific up-regulation of mRNA expression levels of ribonuclease A and collapsin response mediator protein upon the stimulation of imDC with alpha-GalCer, suggesting a novel immunomodulating effect of alpha-GalCer on imDCs. In this study, we used imDCs prepared by culturing of monocytes with GM-CSF and IL-4 for 5 days and mDCs prepared by further culturing of imDCs with TNF alpha for two extra days.

Cell Differentiation↗
PubMed2001

Expression of renin-angiotensin system genes in immature and mature dendritic cells identified using human cDNA microarray.

Using a cDNA glass microarray, the expression of 1081 genes in immature and mature dendritic cells (DCs) of two different individuals has been studied. The upregulation of mRNA transcripts of genes encoding the transcription factor ZFM1, Mos proto-oncogene serine/threonine-protein kinase, B-cell-specific transcription factor, preB-cell growth stimulating factor, ets translocation variant 6, and epidermal growth-factor-like CRIPTO was for the first time detected in DCs. Using semiquantitative RT-PCR analysis the upregulation of the transforming growth factor-alpha, integrin alpha 6 and ZFM 1 transcription factor in mature DCs was confirmed in samples from four different individuals. On the other hand, the downregulation of renin-binding protein transcript was detected in mature DCs using a cDNA microarray. For the first time, the expression of renin-angiotensin system genes was evaluated during maturation of DCs in samples from four donors by semiquantitative RT-PCR. A possible role of the renin-angiotensin system in DCs is discussed.

Antigens, CD↗
PubMed2001

Expression of ID family genes in the synovia from patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by aggressive proliferation of synovial tissue leading to destruction of cartilage and bone. To identify molecules which play a crucial role for the pathogenesis, we compared mRNA expression pattern of RA synovium with that of osteoarthritis (OA), using the differential display. From the panel of differentially expressed genes, ID1 (inhibitor of differentiation 1) was considered to be particularly relevant to the pathogenesis of RA, because Id family genes have been shown to play a role in cell proliferation and angiogenesis. To examine whether the up-regulation of these genes is consistently observed in the patients with RA, mRNA levels of ID1 and ID3 in the synovial tissues from 13 patients with RA and 6 patients with OA were semi-quantitatively analyzed by RT-PCR. Mean mRNA levels of ID1 and ID3 were significantly elevated in RA synovia compared with OA by 8.6-fold (P = 0.0044) and 3.3-fold (P = 0.0085), respectively. Immunohistochemistry revealed striking staining of Id1 and Id3 in the endothelial cells, suggesting a possible role of Id in severe angiogenesis observed in RA. The expression of Id family genes in the synovium constitutes a new finding of particular interest. Their functional role as well as their contribution to the genetic susceptibility to RA requires further investigation.

Aged↗
PubMed2001

Monozygotic twins incompletely concordant for narcolepsy.

BACKGROUND: Among 15 monozygotic twin pairs described in the literature, only four pairs were considered to be concordant. There is no detailed report of HLA-DRB1*1501/DQB1*0602 positive monozygotic twins concordant for narcolepsy, with marked difference in the age of onset. METHODS: We compared a pair of female narcoleptic twins clinically. RESULTS: Diagnosis of narcolepsy and monozygosity of the twins were confirmed. The second-born twin demonstrated a typical course of narcolepsy, whereas the first-born twin had a very late onset of recurrent daytime sleep episodes at age 45 and cataplexy at age 50 years, which was apparently triggered by chronic emotional stresses and sleep insufficiency. CONCLUSIONS: The atypical course of narcolepsy in the first-born twin supports the multifactorial model for the development of narcolepsy. It was noted that cataplexy was preceded by sustained polyphasic sleep conditions. Our observation implies that the unaffected co-twins in discordant pairs could develop narcolepsy in stressful situations later in their lives.

Cytochrome P-450 Enzyme System↗