Treatment of a patient with hemophilia A and hepatitis C virus-related cirrhosis by living-related liver transplantation from an obligate carrier donor

BACKGROUND: Decompensated hepatitis C virus (HCV)-related cirrhosis is the main indication for liver transplantation. We report the first successful living-related liver transplantation in a 49-year-old hemophilia A patient with end-stage HCV-related cirrhosis using a graft obtained from his 20-year-old daughter, an obligate carrier. METHODS: The donor's autologous fresh-frozen plasma rich in factor VIII (FVIII) by treatment with 1-deamino-8-D-arginine vasopressin was prepared before the operation. At induction, 1-deamino-8-D-arginine vasopressin was given to the donor to increase plasma FVIII level. In addition, autologous fresh-frozen plasma containing high FVIII concentrate was infused intraoperatively. The right lobe was harvested from the donor and transplanted orthotopically. The recipient was treated postoperatively with recombinant FVIII and immunosuppressive agents. RESULTS: The donor did not receive recombinant FVIII or allogenic blood during perioperative periods. No bleeding was encountered in the donor perioperatively. The recipient showed a steady increase in FVIII activity postoperatively and was discharged 40 days after transplantation. Ribavirin and interferon-alpha were provided for 3 months postoperatively to prevent potential recurrence of HCV infection. Serum HCV-RNA by RT-PCR became negative after such treatment. CONCLUSIONS: End-stage liver disease in patients with hemophilia A can be an indication for living-related liver transplantation. Furthermore, a graft from a living-related donor with hemophilia A carrier seems to be suitable provided such individuals receive adequate support for coagulopathies.     

Repeated Necrotizing Lymphadenitis with MEFV Gene Mutations

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient''s chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.     

Prevalent founder mutation c.736T>A of LIPH in autosomal recessive woolly hair of Japanese leads to variable severity of hypotrichosis in adulthood

Background Mutations in LIPH are a cause of autosomal recessive woolly hair (ARWH). Homozygous c.736T>A (p.Cys246Ser), and compound heterozygous c.736T>A and c.742C>A (p.His248Asn) have been reported in 5 and 7 Japanese children with ARWH respectively. The severity of hypotrichosis is known to be able to change in the clinical course, and the mutation patterns of LIPH do not always correlate with the severity of hypotrichosis in ARWH caused by other mutation sites of LIPH. However, all 12 Japanese children previously reported to have ARWH have shown similar severity of hypotrichosis. Objective In this study, we investigated the clinical features and molecular basis of ARWH in patients including three adults (three adults and two children) from five non‐related Japanese families. Methods Five families of Japanese origin that presented with woolly hair were studied. The phenotype was confirmed by clinical examination. Direct automated DNA sequencing of the LIPH gene was performed to identify the mutations in our probands. Results All patients had had woolly hair since birth. Homozygous c.736T>A mutations were found in four patients, including three adult cases, and compound heterozygous c.736T>A and c.742C>A mutations were found in one child patient. The two adults and two children had only sparse scalp hair, although one adult woman had mild hypotrichosis with long hairs. Conclusion Some patients with homozygous c.736T>A can have a mild hypotrichosis phenotype with long hairs in adulthood.     

Suppressive Effects of Mometasone Furoate on an Antigen-Specific IgE Antibody Response and Production of IL-4 in Mice

A nasal formulation of mometasone furoate (MF) is advantageous in avoiding systemic activity characteristic of glucocorticoids when it is applied topically. To confirm antiallergic effects of this glucocorticoid formulation elaborately, we investigated whether the drug can suppress the production of IgE antibodies and related cytokines. It we showed that IgE production induced in mice immunized via intranasal route was significantly reduced when the mice were administered MF intranasally. Further, MF was effective in inhibiting production of type-2 helper T cell cytokines in vivo and in vitro. These results provide a immunopharmacological basis for clinical efficacy of this drug.     

Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis

BackgroundPsoriasis is a common chronic inflammatory skin disorder with a high prevalence (3–5%) in the Caucasian population. Although the number of capillary vessels increases in psoriatic lesions, there have been few reports that have specifically examined the role of angiogenesis in psoriasis. Angiogenic factors, such as vascular endothelial growth factor (VEGF), may dominate the activity of anti-angiogenic factors and accelerate angiogenesis in psoriatic skin.ObjectiveWe investigated to identify small peptide mimetics of PEDF that might show anti-angiogenic potential for the topical treatment for psoriasis.MethodsWe examined the expression of PEDF in skin by immunohistochemical staining, immunoblotting, and RT-PCR. To identify potential PEDF peptides, we screened peptides derived from the proteolytic fragmentation of PEDF for their anti-proliferative action. Anti-psoriatic functions of these peptides were analyzed using a mouse graft model of psoriasis.ResultsThe specific low-molecular weight peptides (MW < 850 Da) penetrated the skin and showed significant anti-angiogenic activity in vitro. Topical application of these peptides in a severe combined immunodeficient mouse model of psoriatic disease led to reduced angiogenesis and epidermal thickness.ConclusionsThese data suggest that low-molecular PEDF peptides with anti-angiogenic activity may be a novel therapeutic strategy for psoriasis.     

Enhanced discrimination of single nucleotide polymorphisms using 3′ nucleotide differences in ligase detection reaction probes

The ligase detection reaction (LDR) is a highly specific genotyping method for single nucleotide variations. Although LDR typically discriminates single nucleotide polymorphism (SNP) alleles at the 3′ end of so-called LDR discriminating probes, we designed probes in which the position of nucleotide differences for discrimination was shifted to the second and third nucleotides from the 3′ end. Using the 3′-modified probes, we targeted SNPs of the human ABO group and investigated the specificity and efficiency of ligation by a universal LDR assay. We demonstrated that one or two nucleotide shifts of differences in discriminating probes improve the allele balance in detecting both base substitutions and short deletions. In regard to short deletions, moreover, the shifts of nucleotide differences in discriminating probes form the perfect-machted or multiple-mismatched structures (the bulge structures) in the discriminating probe-target DNA duplex and may contribute to enhance ligation efficiency.     

A randomized placebo-controlled polysomnographic study of eszopiclone in Japanese patients with primary insomnia

ObjectivesTo evaluate the efficacy and dose–response effect of eszopiclone on sleep latency and sleep maintenance in Japanese patients with primary insomnia.MethodsIn this randomized, double-blind, five-way crossover study, 72 patients received placebo, eszopiclone 1 mg, 2 mg, and 3 mg, and zolpidem 10 mg in random order for two consecutive nights with a washout period between treatments. Objective sleep measures from polysomnography (PSG) and subjective patient reports were collected.ResultsAll active treatments produced significant improvement in objective and subjective sleep latency compared with placebo (P < 0.05 for all comparisons); linear dose–response relationships were observed for eszopiclone. PSG-determined wake time after sleep onset (WASO), sleep efficiency, and number of awakenings (NA), and patient-reported measures of WASO, NA, sleep quality, sleep depth, and daytime functioning significantly improved following treatment with eszopiclone 2 mg and 3 mg and zolpidem 10 mg versus placebo (P < 0.05). Eszopiclone at all doses increased total sleep time and stage 2 sleep time (P < 0.001 for both comparisons), but did not alter REM or slow-wave sleep. Eszopiclone was generally well tolerated; the most frequently reported adverse event was mild dysgeusia.ConclusionsIn Japanese patients with primary insomnia, eszopiclone 2 mg and 3 mg significantly improved PSG-determined and patient-reported sleep latency and sleep maintenance relative to placebo.