Primary cutaneous coccidioidomycosis

Primary cutaneous coccidioidomycosis is usually secondary to laboratory or autopsy inoculation, but can result from trauma in endemic areas. We describe an unusual case of primary inoculation cutaneous coccidioidomycosis occurring in an immunocompetent woman in a nonendemic area. The clinical features, diagnostic tests, and therapy of this extremely rare disease are reviewed.     

Intercellular junctions in the follicular envelope of the teleost, Brachydanio rerio

The nature and distribution of intercellular junctions in the outer ovarian epithelium (serosa, mesothelium), endothelium, and follicle cells of the teleost oocyte-follicle complex were investigated by freeze-fracture electron microscopy. Tight-junctions were common between outer squamous epithelial cells, sometimes closely associated with intercalated foci of communicating junctions. The tight junctions consisted of one to several sealing strands which possessed focal discontinuities. In addition, the strands existed as loops or as short, free-ending elements; a condition that could indicate lability in their assembly or disassembly. The presence of free-ending strands could also mean that the structure serves for attachment as well as involved in the formation of occluding zonules. The free ends of some bars comprising the tight junctional strands are enlarged slightly. In outer ovarian epithelial or serosal cells, as is the case for mammalian mesothelium described by others, clusters of particles comprising communicating (gap) junctions are often intercalated within or are located in close proximity to tight junctional strands. In freeze-cleaved replicas, the outer squamous epithelial (serosal) cells contained a multitude of micropinocytotic pits (caveolae) and vesicles. Capillary endothelium also contains tight junctional components which are often closely associated with communicating junctions. Tight junctions also exist between follicle cells, but their structure changes during oocyte growth. Communicating junctions between follicle cells tend to be focal in distribution and not closely associated with tight junctions.     

Failure to detect association between polymorphisms of the sodium channel gene SCN1A and febrile seizures in Chinese patients with epilepsy

A recent study in Caucasians found an association between the single nucleotide polymorphism (SNP) of SCN1A, IVS5N +5 G>A (rs3812718), and febrile seizures (FS). We examined whether this and other tagging SNPs of SCN1A were associated with an increased risk of FS in Han Chinese. A total of 728 Han Chinese patients with focal epilepsy were recruited: 97 had a history of FS (58% male, mean age 35 ± 12 years) and 631 did not (50% male, mean age 40 ± 15 years). Genotyping was performed for IVS5N +5 G>A and seven other tagging SNPs selected from the HapMap database. Genotyping was also performed in 848 ethnically matched population controls (50% male, mean age 37 ± 17 years). There was no statistically significant difference in either allele or genotype frequency of any of the SNPs studied between epilepsy patients with and without FS, and between epilepsy patients with FS and controls. The results do not suggest that SCN1A SNPs are susceptibility factors for FS in Han Chinese.     

Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: Incidence, associated factors and prognosis

Abstract Background and Aims: Interferon (IFN) plus ribavirin therapy for chronic hepatitis C (CHC) virus infection has been associated with thyroid dysfunction. The goal of our current study was to elucidate predictive factors of: (i) thyroid dysfunction associated with combination therapy; and (ii) long‐term reversibility of thyroid dysfunction. Methods: In total, 461 patients with CHC and normal baseline thyroid functions were enrolled. All patients received IFN‐α‐2b, 3 or 5 million units thrice weekly, or pegylated (PEG)‐IFN‐α‐2b 80 or 100 µg weekly combined with ribavirin 1–1.2 g daily for 24–48 weeks. Assays for serum thyroid stimulating hormone (TSH) and free thyroxine were performed. Results: By the end of the treatment, thyroid dysfunction (TSH <0.1 or >5 mU/L) had developed in 58 patients (12.6%). Female gender was significantly associated with thyroid dysfunction (P < 0.001 odds ratio (OR) = 2.85; 95% confidence interval (CI) = 1.6–5.1). The incidence of thyroid dysfunction was similar for standard IFN and PEG‐IFN‐treated patients (49/391 vs 9/70; P = 1.00). Under a nested case‐control design, detailed laboratory assessment was carried out on frozen serum samples from patients and age‐ (± 5 years) and sex‐matched controls (n = 58). Multivariate analysis revealed significant association between higher positive rates of pretreatment TMA and patients who developed thyroid dysfunction (OR = 5.8, 95% CI = 1.2–27.9). Ten patients (～2%) remained thyroid dysfunctional at the end of follow up (median, 26.5 months). For these patients, no risk factor can predict the reversibility of thyroid function. Conclusions: Female gender and pretreatment TMA positivity are associated with thyroid dysfunction. Long‐term thyroid dysfunction may persist in a small group of patients (～2%).     

Changing distribution of norovirus genotypes and genetic analysis of recombinant GIIb among infants and children with diarrhea in Japan

A total of 402 fecal specimens collected during July 2003-June 2004 from infants and children with acute gastroenteritis, encompassing five localities (Maizuru, Tokyo, Sapporo, Saga, and Osaka) of Japan, were tested for the presence of norovirus by RT-PCR. It was found that 58 (14.4%) fecal specimens were positive for norovirus. Norovirus infection was detected throughout the year with the highest prevalence in December. Norovirus GII was the most predominant genogroup (98.3%; 57 of 58). The genotypes detected in this study were GI/4, GII/2, GII/3, GII/4, and GII/6. Of these, NoV GII/3 (known as the Arg320 virus cluster) was the most predominant genotype (43.9%), followed by NoV GII/4 (the Lordsdale virus cluster; 35.1%) and others. Two norovirus strains clustered with a "new variant designated GIIb" and a "new variant of GII/4" were found circulating in Japan for the first time. It was interesting to note that NoV GIIb and NoV GII/3 appeared to be the recombinant strains and the recombination site was demonstrated at the overlap of ORF1 and ORF2. The majority (96%) of the dominant norovirus strains were identified as the recombination of GII/3 capsid and GII/12 polymerase. The recombination in the NoV GIIb capsid gene at the breakpoint located at P1 domain was also identified. Obviously, NoV GIIb isolate in Japan had double recombination. This is the first report demonstrating the existence of different "new variants" co-circulating in Japanese infants and children with acute gastroenteritis.     

Progestin-based contraceptive suppresses cellular immune responses in SHIV-infected rhesus macaques

Nine rhesus macaques in groups of three received a single dose of the injectable progestin-based contraceptive Depo-Provera 5 weeks prior to challenge intravaginally with varying doses of a mixture of the pathogenic CXCR4 (X4)-SHIV(SF33A) and CCR5 (R5)-SHIV(SF162P3) isolates. As controls, seven Depo-naive animals were inoculated once with a high-dose of the mixed inoculum. Irrespective of inoculum dose, acute viremia was higher in the Depo-treated than in the Depo-naive animals. Further, genetic complexity of the replicating virus was greater and replication of the X4 virus was favored in dually infected animals treated with Depo-Provera. Analysis of cellular immune responses revealed slower response rates in virus-specific IFN-gamma production to SIV Gag in the Depo-treated macaques. The immunosuppressive effect of Depo-Provera on mounting an antiviral cellular immune response may account for the increase viral burden and diversity, and the predominance of X4 virus replication in SHIV infected macaques that were administered the progestin-based contraceptive.