Implications of Popliteal Lymph Node Detected by Sentinel Lymph Node Biopsy

BACKGROUND: Although there is lymphatic flow into the popliteal fossa from a skin tumor located in the lower leg, popliteal metastasis is extremely rare. Recently, sentinel lymph nodes outside traditional nodal basins have been identified. This study investigated the incidence of sentinel nodes in the popliteal region and the indication for biopsy. METHODS: Fourteen patients with various skin cancers involving the lower extremities (nine melanomas, four squamous cell carcinomas, and one sweat gland carcinoma) underwent lymphoscintigraphy and excision with sentinel lymph node biopsy. RESULTS: In all 14 patients, hot spots showed accumulation in the groin region. Five of 14 patients (36%) demonstrated popliteal sentinel nodes in addition to the inguinal nodes. Three of five popliteal sentinel nodes were histologically studied. A patient with acral melanoma demonstrated micrometastasis of melanoma cells in a popliteal node but not in the groin node. CONCLUSION: This study demonstrates that sentinel lymph nodes located in the popliteal fossa are frequently detected by lymphoscintigraphy and that biopsy should be performed if popliteal nodes are identified.     

Gene organization of HLA and its association with ocular disease]

It is now evident that the human major histocompatibility complex (MHC), human leucocyte-associated antigen (HLA), regulates the immune response through discrimination between autologous and non autologous substances thereby displaying a high degree of genetic polymorphism. In recent years, the three-dimensional structure of HLA has been clarified by crystal analysis and provides the attractive hypothesis, the so-called hotdog model, explaining the interactions of foreign antigens (or autologous antigens), HLA and T cell receptors and has a great impact on various studies on immunogenetic mechanisms underlying the development of many diseases. Thus, several HLA-associated ocular diseases such as Beh?et's disease and Harada's disease have also been analyzed from this point of view by means of recombinant DNA techniques, enabling elucidation of molecular mechanisms of susceptibility to these diseases. This paper describes a general outline of HLA, especially its genetical structure, as well as recent analysis of molecular mechanisms of the predisposition to representative ocular diseases.     

Modified PCR-RFLP method for HLA-DPB1 and -DQA1 genotyping.

We previously developed a new technique for HLA class II genotyping by digestion of polymerase chain reaction-amplified genes with restriction endonucleases (PCR-RFLP method). This PCR-RFLP method is an efficient and convenient typing technique for class II alleles. However, small fragments or bands located close to each other on polyacrylamide gels sometimes prevent precise analysis of the RFLP bands. Furthermore, the restriction enzymes we have reported in the previous papers are not sufficient to identify the genotypes of all heterozygous individuals. Here, we report an improved PCR-RFLP method using some informative restriction enzymes which have either a single cleavage site or, alternatively, no cleavage site in the amplified DNA region, depending on the HLA alleles, making reading of RFLP band patterns much easier. Each second exon of the HLA-DQA1 or -DPB1 gene was selectively amplified from genomic DNAs of 70 HLA-homozygous B-cell lines and 100 healthy Japanese by PCR. Amplified DNAs were digested with restriction endonucleases and then subjected to electrophoresis assaying simply for cutting, or no cutting, of the DNA. ApaLI, HphI, BsaJI, FokI, MboII and Mn1I can discriminate eight alleles of the DQA1 gene. Similarly 19 alleles of the DPB1 gene can be discriminated with Bsp1286I, FokI, DdeI, BsaJI, BssHII, Cfr13I, RsaI, EcoNI, and AvaII enzymes. This modified PCR-RFLP method can be successfully applied to heterozygotes. Thus, the method is technically simpler and more practical for routine HLA typing work than our previous PCR-RFLP method.     

Host resistance to Listeria monocytogenes infection is enhanced but resistance to Staphylococcus aureus infection is reduced in acute graft-versus-host disease in mice

Acute graft-versus-host disease (GVHD) is characterized by the production of high levels of T helper 1 (Th1)-type cytokines. Bone marrow transplantation from allogeneic C57BL/6 cells to CBF(1) mice produced acute GVHD. Host resistance to Th1-driven Listeria monocytogenes was enhanced, whereas host resistance to Th2-driven Staphylococcus aureus was reduced during acute GVHD. These results suggest that opposite host responses are observed between Th1-driven and Th2-driven bacterial infections in acute GVHD.     

HLA class I genotyping including HLA-B*51 allele typing in the Iranian patients with Behçet's disease

It is well known that Beh?et's disease (BD) is strongly associated with human leukocyte antigen (HLA) B51 in many ethnic groups. However, there has been no published report as yet with respect to this association among the Iranian people. Furthermore, since it is now known that the B51 antigen can be encoded by 21 alleles, B*5101-B*5121, we performed HLA-B*51 allele typing as well as HLA class I genotyping of 48 Iranian patients with this disease. As a result, the frequency of the B*51 allele was significantly higher (62.1%) in the patient group as compared with the ethnically matched control group (31.8%) (Pc=0.067, R.R.=3.51). In the genotyping of B*51 alleles, 33 out of the 36 B*51-positive patients possessed B*5101 and the remaining 3 carried B*5108. This study revealed that Iranian patients with BD also had a strong association with HLA-B51. In addition, this significantly high incidence of HLA-B*51 was found to be caused by an increase in both the HLA-B*5101 and HLA-B*5108 alleles. However, there was no significant difference in the HLA-B*51 allelic distribution between the patient and control groups.     

Significant associations of HLA-B*5101 and B*5108, and lack of association of class II alleles with Behçet's disease in Italian patients

Beh?et's disease has been known to be strongly associated with human leukocyte antigen (HLA) B51, one of the split antigens of HLA-B5. An increased incidence of HLA-B51 in the patient group has also been reported in an Italian population. Since the B51 antigen has been recently identified to comprise nine alleles, B*5101-B*5109, we performed HLA-B51 allele genotyping by the polymerase chain reaction-sequencing based typing (PCR-SBT) method as well as serological HLA-A and -B typing among 21 Italian patients with Beh?et's disease in order to investigate whether there is any correlation of one particular B51-associated allele with Behcet's disease. In addition, HLA class II genotyping was performed by the PCR-restriction fragment length polymorphism (RFLP) method. As a result, only the phenotype frequency of the B51 antigen was found to be significantly increased in the patient group as compared to the ethnically matched control group by the corrected P-value analysis (71.4% in patients vs. 17.9% in controls; chi2 = 14.26, Pc = 0.0042, R.R. = 11.5). In the B51 allele genotyping, 11 out of 15 B51-positive patients were B*5101 and the remaining four were B*5108, whereas all of 5 normal controls were B*5101, showing significant association of each allele with Beh?et's disease. No significant difference was observed between the patient and control groups in the HLA class II allelic distribution. This study revealed a strong association of Beh?et's disease in Italian with B*5108 as well as B*5101, providing important insight into the molecular mechanism underlying an HLA association with Beh?et's disease.     

Association of gastric epithelial apoptosis with the ability of Helicobacter pylori to induce a neutrophil oxidative burst

Both polymorphonuclear cell infiltration and increased epithelial apoptosis are seen in gastric mucosa in the presence of Helicobacter pylori infection. This study examined the association between bacterial ability to stimulate an oxidative burst in neutrophils and epithelial apoptosis. Biopsy specimens were obtained from 15 patients to detect apoptotic cells by the TUNEL method. H. pylori strains isolated from corresponding stomach biopsy samples were tested for the ability to stimulate an oxidative burst in human neutrophils. Neutrophils were isolated from healthy subjects without H. pylori infection and the oxidative burst was measured by flow cytometry with dichlorofluorescein diacetate. Stimulation with H. pylori increased both the percentage of activated cells and fluorescence intensity. There was a significant positive correlation between the number of epithelial apoptotic cells and fluorescence intensity. Increased neutrophil oxidative burst stimulated by H. pylori may play a role in enhanced gastric mucosal DNA damage and consequent atrophic gastritis and gastric cancer.     

Management of lung transplantation in the COVID-19 era—An international survey

It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19.     

New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates

The threat of the current coronavirus disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is accelerating the development of potential vaccines. Candidate vaccines have been generated using existing technologies that have been applied for developing vaccines against other infectious diseases. Two new types of platforms, mRNA- and viral vector-based vaccines, have been gaining attention owing to the rapid advancement in their methodologies. In clinical trials, setting appropriate immunological endpoints plays a key role in evaluating the efficacy and safety of candidate vaccines. Updated information about immunological features from individuals who have or have not been exposed to SARS-CoV-2 continues to guide effective vaccine development strategies. This review highlights key strategies for generating candidate SARS-CoV-2 vaccines and considerations for vaccine development and clinical trials.