HLA-Bw54-DR4-DRw53-DQw4 haplotype controls nonresponsiveness to hepatitis-B surface antigen -via CD8-positive suppressor T cells

We have previously reported that in nonresponders to hepatitis-B (HB) vaccine there was an HLA-linked immune suppression gene for hepatitis-B surface antigen (Is-HBsAg) controlling the nonresponsiveness to HBsAg, through HBsAg-specific suppressor T cells, and that the Is-HBsAg was in strong linkage disequilibrium with the HLA-Bw54-DR4-DRw53 haplotype (1). We have now done the HLA typing on an additional 6 nonresponders, and using the system of T-cell proliferative response to HBsAg we found that the Is-HBsAg controlled the nonresponsiveness to HBsAg through HBsAg-specific suppressor T cells in nonresponders to HB vaccine who have HLA-Bw54-DR4-DRw53-DQw4 haplotype. T- and B-cell recognition of HB vaccines might play an important role at 3 to 5 weeks after the last immunization. Use of an anti-HLA monoclonal antibody has shown that the HLA-DR molecule plays an important role in helper T-cell proliferation in nonresponders, although the role of HLA-DQ molecule in nonresponders was unclear.     

Antisense in vivo knockdown of synaptotagmin I and synapsin I by HVJ-liposome mediated gene transfer modulates ischemic injury of hippocampus in opposing ways

Neurotransmitter release during and after ischemic event is thought to be involved in excitotoxicity as a pathogenesis for the ischemic brain damage, which is mediated by excessive activation of glutamate receptors and attendant calcium overload. To ascertain the role of transmitter release from nerve terminals in promoting the ischemic neurodegeneration, we delivered antisense oligodeoxynucleotides (ODNs) to synaptotagmin I or synapsin I into the rat brain by using HVJ-liposome gene transfer technique. The antisense ODNs were injected into the lateralventricle in rats 4 days prior to transient forebrain ischemia of 20 min. With a single antisense treatment, long-lasting downregulation of the transmitter release relating protein levels at overall synaptic terminals was achieved. The antisense in vivo knockdown of synaptotagmin I prevented almost completely the ischemic damage of hippocampal CA1 neurons, while the in vivo knockdown of synapsin I markedly promoted the ischemic damage of CA1 pyramidal neurons and extended the injury to relatively resistant CA2/CA3 region. The modulation of ischemic hippocampal damage by the in vivo knockdown of synaptotagmin I or synapsin I suggests that transmitter release from terminals plays an important role in the evolution of ischemic brain damage and therefore the transmitter release strategy by the use of antisense ODNs-HVJ-liposome complex is reliable for neuroprotective therapies.     

Genetic analysis of subacute (de Quervain''s) thyroiditis

A weak association between subacute (de Quervain's) thyroiditis and HLA-DRw8 (relative risk = 2.19, X2 = 3.86) was observed. However, the association was not statistically significant if p value was corrected. Since it was confirmed that the association of subacute thyroiditis with HLA-B35 was primary, and since this association was extremely strong, the two models (dominant and recessive) for the effect of an HLA-linked gene which has a major effect on the pathogenesis of subacute thyroiditis were tested by the method described by Thomson & Bodmer using the frequency of HLA-B35 in the patients. The data most fit to the recessive model for the HLA-linked major gene involved in subacute thyroiditis.     

DNA typing of HLA class I (HLA-A) and class II genes (HLA-DR, -DQ and -DP) in Japanese patients with gastric cancer

Gastric cancer is multifactorial disease and several reports have described genetic factors involved in pathogenesis of gastric cancer. Recently, it was reported that HLA class II gene DQB1*0301 was strongly associated with gastric cancer in Caucasian population (20). We performed DNA typing of HLA class I (HLA-A) and HLA class II genes (HLA-DR, DQ and DP) to elucidate the HLA alleles or HLA haplotypes associated with gastric cancer in Japanese population using polymerase chain reaction-sequence-specific oligonucleotide probe analysis in 88 unrelated patients with gastric cancer and 525 unrelated healthy controls. We observed slight difference in frequencies of some HLA alleles and haplotypes between gastric cancer patients and controls; however, after Bonferroni correction, statistical significance was not confirmed. It is possible that environmental factors such as diet cover the contribution of genetic factors to the disease in Japanese population, which has a higher frequency of gastric cancer than do Caucasian populations, most likely due to more exposure to environmental risk factors.     

Interactive effect of Gm and Km allotypes on cellular immune responses to streptococcal cell wall antigen

Serum samples from 121 unrelated, healthy Japanese individuals were typed for several Gm and Km(1) allotypes. Peripheral blood lymphocytes from these subjects were cultured with streptococcal cell wall (SCW) antigen and the incorporation of 3H-thymidine into T lymphoblasts was measured. Log-linear analysis showed a significant interactive effect of Gm1,17;13,16,21 and Km(1) on the cellular immune response to group A SCW antigen.     

Family analysis of Werner's syndrome: A survey of 42 Japanese families with a review of the literature

Forty-two Japanese families, including 80 individuals with Werner's syndrome were studied, confirming that this syndrome is inherited as an autosomal recessive trait. The incidence of malignancy was relatively high in these families and individuals with Werner's syndrome, although the incidence was not so high as was reported previously. HLA typing revealed no significant linkage with Werner's syndrome. The frequency of Werner's syndrome in Japan was estimated using two methods which indicated approximately 300 cases among 100 million people.     

Attitudes toward cancer screening in regional Japan during the COVID-19 pandemic: An anonymous survey

The coronavirus disease (COVID-19) pandemic has raised concerns about the impact of delayed health check-ups and cancer screenings on cancer diagnosis and treatment. This study aimed to investigate the awareness of cancer patients on future screening measures during the pandemic in rural Japan. An anonymized open-data survey was undertaken in Fukui Prefecture, a rural region of Japan, in 2021. Participants were asked about their cancer screening history, screening frequency during the pandemic, and reasons for not undergoing screening. Among the 1262 respondents, the proportion of patients who underwent cancer screening in 2020 during the pandemic was similar to the proportion who underwent regular (annual or biannual) screening in 2019 before the pandemic. Of those who underwent regular screening, 82% still underwent screening in 2020, while only 21% of those who had irregular screenings. The number of respondents who believed they were healthy and did not require screening increased over time, possibly due to restrictions on going out and refraining from activities during the pandemic. This study in rural Japan found that regular cancer screening prior to the pandemic was associated with a more positive attitude toward screening during the pandemic. Raising awareness about the importance of cancer screening and encouraging participation is crucial for promoting positive attitudes in the future. The findings highlight the need for continued efforts to ensure access to screening services during the pandemic and future public health emergencies.