Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus

PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation.     

Involvement of NF-kappaB and mitochondrial pathways in docetaxel-induced apoptosis of human oral squamous cell carcinoma

Apoptosis induced by docetaxel that interferes with microtubule polymerization dynamics and is used clinically to treat advanced cancers, has not been fully defined in squamous cell carcinoma. In this study, apoptotic events involved in docetaxel treatment were investigated. When the human oral squamous cell carcinoma cell line HSC-3 was exposed to docetaxel for 72 h, a dose-dependent effect was observed in apoptosis using the TUNEL method. We observed activation of caspase cascade including activities like caspase-3, -8, and -9. And the pan-caspase inhibitor z-VAD-fmk prevented apoptosis induced by docetaxel (0.1 microM), showing participation of caspases in this process. Since an antagonistic CD95-antibody (ZB4) exerted no effect on docetaxel-induced apoptosis, CD95/CD95L interaction was not involved in this pathway. The caspase-8-like activity was inhibited not only by IETD-fmk (caspase-8) but also by DEVD-fmk (caspase-3). The results indicate that the caspase-8-like activation occurred downstream of DEVDase. Docetaxel promoted the formation of reactive oxygen species (ROS) in mitochondria, and preincubation of cells with anti-oxidants such as N-acetyl cysteine and pyrrolidine dithiocarbamate, protected against apoptosis mediated by docetaxel. Furthermore, treatment with docetaxel elicited reduction of mitochondrial membrane potential, and release of cytochrome c to cytosol, after 48 h of treatment. We observed binding activity to NF-kappaB consensus site and interference with the mitochondrial function via NF-kappaB after docetaxel treatment. Preventing pro-apoptotic property of NF-kappaB inhibited docetaxel-induced apoptosis. Thus, these results suggest that, following the activation of NF-kappaB by docetaxel, apoptosis is elicited through a mitochondria-dependent pathway.     

Subjects with <Emphasis Type="Italic">TNF-A-857TT</Emphasis> and <Emphasis Type="Italic">-1031TT</Emphasis> genotypes showed the highest <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositive rate compared with those with other genotypes

Background A possible association between Helicobacter pylori seropositivity and tumor necrosis factor (TNF) A G-308A has been reported in Korea. The present study examined the associations of H. pylori with functional polymorphisms, TNF-A G-308A, C-857T, and T-1031C, and TNF-B A252G in Japanese subjects.Methods The total of 1374 study subjects included 241 outpatients who participated in an H. pylori eradication program (HPE), 679 first-visit outpatients (FVO) at a regional cancer hospital, and 454 local residents who received a health checkup examination (HCE).Results The frequency of the TNF-A -308A allele was only 1.3% of 480 chromosomes in the HPE group, so the FVO and HCE groups were not genotyped for that polymorphism. The genotype frequency of TNF-A C-857T was 69.2% CC, 27.7% CT, and 3.1% TT; that of TNF-A T-1031C was 69.4% TT, 28.1% TC, and 2.5% CC; and that of TNF-B A252G was 36.8% AA, 48.2% AG, and 15.0% GG. TNF-A -857T was tightly linked to TNF-A -1031T and TNF-B 252A. No significant associations between H. pylori seropositivity and polymorphisms of TNF-A C-857T and TNF-B A252G were observed. However, a reduced odds ratio adjusted for sex, age, and recruitment source was observed for TNF-A -1031CC (0.43; 95% confidence interval, 0.20–0.91) relative to TNF-A -1031TT. Subjects with TNF-A -857CC and -1031CC showed the lowest seropositivity (38.2% of 34 participants), while those with TNF-A -857TT and -1031TT showed the highest (66.7% of 42 participants).Conclusions This study suggests that the possibly high expression genotype of TNF-A may increase susceptibility to persistent H. pylori infection.     

Identification of Factors Necessary for Enabling Technology-Based Dietary Record Surveys: A Qualitative Focus Group Interview with Japanese Dietitians

Weighed food records together with an in-person interview approach constitute the most basic methods used to estimate energy and nutrient intakes in dietary surveys. In the background of the coronavirus disease-2019 pandemic, the need for non-face-to-face dietary surveys using information and communication technology (ICT) is increasing. We aimed to evaluate ICT-based dietary record surveys and identify factors that may enable this survey method to become more widely used in the future. We conducted a non-face-to-face survey of dietary records of 44 Japanese individuals, maintained by dietitians using dietary photography and video conferencing services. We conducted a focus group interview with the six dietitians who conducted that survey. Their opinions on the factors necessary to popularize ICT-based dietary survey method were analyzed. In the focus group interview, dietitians highlighted fewer restrictions on time and place as positive aspects. Negative aspects included insufficient skills to operate computers, difficulty in hearing, and understanding facial expressions using ICT. We identified three main factors for enabling widespread use of ICT-based dietary record survey: individual skill, device and technology, and social environmental factors. This suggests that a comprehensive approach is necessary for popularizing the use of ICT in dietary surveys.     

In vivo effect of methylmercury on protein synthesis in brain and liver of the rat

Rats were given daily sc injections of methylmercury chloride, 10 mg/kg for 7 consecutive days. The manifestation of the neurological syndrome in the rat and the accumulation of mercury in rat tissues resembled the observations of previous investigators. The incorporation in vitro of [¹⁴C]leucine into brain protein began to decrease during the latent period of intoxication and declined to 56% of the control values at the symptomatic period. The incorporation of [¹⁴C]leucine into liver protein was also inhibited to a similar extent at the symptomatic period following a remarkable stimulation at the early stage after the onset of administration of methylmercury. The impairment of protein synthesis in the brain and liver at the symptomatic period was confirmed by the incorporation in vivo of a ¹⁴C-labeled amino acid mixture into proteins of these tissues. The decrease in the [¹⁴C]leucine incorporation in the liver of poisoned rats was largely affected by nutritional deficiency due to decreased food intake, but that in the brain resulted from the direct effect of methylmercury on this tissue.     

Chronic Alcohol Abuse Leads to Gastric Atrophy and Decreased Gastric Secretory Capacity: A Histological and Physiological Study

We performed morphological and physiological studies in 43 male patients with alcohol dependence (ALC) who had no other apparent lesions in the upper gastrointestinal tract except atrophic and erosive gastritis. A gastric secretory study in which tetragastrin was used as the stimulant revealed that acid and pepsin secretion was less in ALC patients than in hospital controls (p less than 0.001). Endoscopic biopsy specimens of gastric mucosa from ALC patients revealed that atrophy of the gastric mucosa advanced with age. A strong negative correlation was also found between the secretory capacity of the stomach and the degree of atrophy. Possibly, the interval between recurrent episodes of acute mucosal damage was too short to allow complete healing of mucosal lesions. Failure to regenerate denuded epithelium would result in a decrease in the gastric secretory area. Thus, chronic alcohol abuse seems to be an etiological factor in atrophic gastritis.     

Regression of superficial gastric MALT lymphoma with unsuccessful eradication therapy forHelicobacter pylori infection

A 51-year-old man had a reddish flat granular lesion in the stomach on endoscopic examination. Histology of biopsied specimen confirmed the diagnosis of low-grade B-cell gastric lymphoma of mucosaassociated lymphoid tissue (gastric MALT lymphoma) and simultaneous infection withHelicobacter pylori. He was given antibiotic treatment. Five weeks later, endoscopy and histology of biopsied specimen showed eradication ofH. pylori, and the tumor had regressed. Six months later,H. pylori reemerged, but the tumor had not recurred. After the second antibiotic therapy,H. pylori has been eradicated. The lymphoma has been in remission for 14 months.