Possible Associations between HLA Antigens and the Immune Responsiveness to Attenuated Rubella Vaccine

We investigated the possible associations between HLA antigens and the antibody response patterns during a clinical trial with a live attenuated rubella vaccine in 172 Japanese schoolgirls. Those vaccine recipients were divided into three groups, 42 low responders, 102 intermediate responders and 28 high responders, according to convalescent-phase hemagglutination-inhibiting antibody titers. High frequencies of HLA--A11 and HLA--B15 in high responders and HLA--Aw24 and HLA--B5 in low responders were found. Among HLA--A antigens HLA--A11 had the highest geometric mean HI antibody titer and HLA--Aw24 had the lowest. Among HLA--B antigens HLA--B15 had the highest and HLA--B5 had the lowest. Strong linkage disequilibrium was found between HLA--A11 and HLA--B15 in high responders and between HLA--Aw24 and HLA--B5 in low responders. These results suggest that there may be a relationship between HLA antigens and specific immune response genes in man as well as in other vertebrates.     

Chromosome rearrangements at 12q13 in two cases of chondrosarcomas.

We analyzed the karyotypes of two moderately differentiated (grade 2) chondrosarcomas. Case 1 had a reciprocal translocation between chromosomes 6 and 12, t(6;12)(q25;q13) in most of the cells analyzed, as well as trisomies of chromosomes 7, 8, 11, 17, 19, and 21 and tetrasomy of chromosome 19. A reciprocal translocation involving chromosomes 12 and 19, t(12;19)(q13;q13), was noted as a highly clonal abnormality in the other case. Some cells had t(12;19) as the sole chromosome abnormality. Thus, chromosome rearrangements involving the long arm of chromosome 12 at the same region (q13) were commonly identified in the two tumors. These findings suggest that the rearrangements at 12q13 are nonrandom acquired changes that characterize a subgroup of chondrosarcomas.     

Immune Complex-induced Disseminated Intravascular Coagulation (DIC) An Experimental Study

Disseminated intravascular coagulation (DIC) was induced in rabbits by administration of antibody and antigen. The rabbits were sensitized passively by i.v. injection of antiferritin antiserum and challenged simultaneously by an i.p. inoculation of ferritin. After the challenge, circulating white blood cells, platelets and plasma fibrinogen levels showed an early fall, reaching minimum values at 3,10 and 6 h, respectively. Fibrin thrombi appeared first at 2 h, reached a maximum at 5–7 h, and had mostly disappeared by 24 h. Formation of fibrin thrombi was frequent in the lung, liver, kidney and spleen. Early morphological changes included neutrophilic infiltration and accumulation of platelets in capillaries. Ferritin antiferritin complexes were noted among fibrin thrombi or phagocytized by reticuloendothelial cells and neutrophils. The capacity of Kupffer cells to remove circulating immune complexes was saturated transiently; at this time fibrin thrombosis in various organs was most widespread and severe. It seems likely that formation of antigen-antibody complexes in the microcirculation initiates activation of platelets and neutrophils with subsequent release of mediators responsible for triggering DIC. Activation of complement was another possible factor inducing the reaction. In addition, blockade of the reticuloendothelial system promotes the progression of DIC. It is considered that the methods described constitute a useful model for further elucidation of immune complex induced DIC.     

Molecular characterization of inv dup del(8p): analysis of five cases

We analyzed five patients with inverted duplication deletion of 8p [inv dup del(8p)] using fluorescence in situ hybridization (FISH) and short tandem repeat polymorphism (STRP) analysis. In all patients, inv dup del(8p) consisted of a deleted distal segment, an intact in-between segment, and a duplicated proximal segment. In all of them, the proximal breakpoint of the deletion and one of the breakpoints of the duplication were identical, each located at one of the two olfactory receptor gene clusters at 8p23. FISH analysis showed all their mothers to be heterozygous carriers of an 8p23 inversion [inv(8)(p23)]. STRP analysis indicated that the deletions occurred in maternally derived chromosomes. The duplicated segments had two copies of maternal, either heterozygous or homozygous alleles. These findings support and reinforce those in 16 patients with inv dup del(8p) and their parents by Floridia et al. [1996: Am J Hum Genet 58:785-796] and subsequent additional studies of 10 of them by Giglio et al. [2001: Am J Hum Genet 68:874-883]. Based on these findings, we propose a model for the inv dup del(8p) formation. The inverted segment and its normal counterpart in inv(8)(p23) heterozygous carrier mothers form a loop at the pachytene period of meiosis I. Inv dup del(8p) with heterozygous duplication is formed through at least one meiotic recombination within the loop. Inv dup del(8p) with the homozygous duplication arises through two meiotic recombinations on the inv(8)(p23) chromosome (one within the loop and the other between the loop and centromere). Subsequent rescue by eliminating a part of the duplicated segment and a centromere enables formation of viable inv dup del(8p). The frequency of the inv(8)(p23) allele is 39% in a normal Japanese population, comparable to 26% in Europeans Giglio et al. [2001: Am J Hum Genet 68:874-883]. The proposed mechanism of formation of inv dup del(8p) requires two independent events (a recombination within the loop and subsequent rescue), which may explain its rarity.     

Comparison between single and double suture passing techniques in the suture bridge rotator cuff repair with a 2-mm tape: A simulation study using a three-dimensional finite element method

BackgroundSuture bridge repair has been widely used as one of the standard procedures in the arthroscopic rotator cuff repair. We compared the intratendinous stress distribution between single and double suture passing techniques in the suture bridge repair using a 2-mm tape and clarified the roles of tensioning in this procedure.MethodsA board-like model of the supraspinatus tendon and humeral head was used in order to standardize conditions and exclude the influence of anatomical variations between individuals. Reattachment of the supraspinatus tendon to the bone was simulated using both single and double suture passing techniques for the suture bridge repair using a 2-mm tape. A tensile load was applied to the medial end of the tendon, and the stress distribution pattern was observed. Elastic analysis enabled comparison of the von Mises equivalent and maximum principal stresses between the single and double suture passing techniques. The tape configuration was subsequently translated 1 mm toward the insertion points of lateral anchors to simulate the tensioning maneuver.ResultsAlthough the distribution pattern of both the equivalent and the maximum principal stresses was similar for both models, areas with a high stress concentration were smaller in the single suture passing model than those in the double suture passing model. The equivalent stress concentrated within the tendon beneath the tapes as well as in the area between the crossing tapes and the lateral end of the tendon, whereas the maximum principal stress concentrated medial to the sites of suture penetration.ConclusionsSingle suture passing technique can reduce the extent of intratendinous stress concentration compared with double suture passing technique, which might be beneficial to reduce the incidence of type 2 retear after suture bridge repair of rotator cuff tendon using a 2-mm tape.     

Correlation between CXCR4/CXCR7/CXCL12 chemokine axis expression and prognosis in lymph‐node‐positive lung cancer patients

The CXCR4/CXCR7/CXCL12 chemokine axis plays important roles in the migration of tumor cells during cancer development by modulating site‐specific distant metastasis including to regional lymph nodes. We investigated the correlation of these chemokine expressions to prognosis in lymph‐node‐positive non‐small‐cell lung cancer (NSCLC) patients. A total of 140 surgically resected specimens of primary site (PS) and metastatic lymph nodes (MLN) of NSCLC involving hilar and/or mediastinal lymph nodes (N1‐2) were collected. CXCR4, CXCR7 and CXCL12 expressions were evaluated. Cox regression analysis was performed to determine whether these chemokines were independent prognostic factors in N1‐2 NSCLC. High expression of CXCR4 in PS and CXCL12 in MLN was associated with poor overall survival (OS) (P = .025 and .033, respectively). Significant correlations between CXCR4 expression in PS and CXCL12 expression in MLN were observed (P = .040). There was significant difference in OS between 2 groups according to expressions of CXCR4 in PS and CXCL12 in MLN (P = .0033). Expression of CXCL12 in MLN was identified as an independent prognostic factor (HR 1.79, 95% CI 1.08‐3.04, P = .023). CXCL12 in MLN was mainly expressed by tumor cells compared with stromal cells (56% vs 25%, respectively, P < .0001). CXCR4/CXCL12 may play roles in tumor progression in MLN and is associated with poor prognosis of lymph‐node‐positive NSCLC patients.     

Characteristics of <Emphasis Type="Italic">MUTYH</Emphasis> variants in Japanese colorectal polyposis patients

Background

The base excision repair gene MUTYH is the causative gene of colorectal polyposis syndrome, which is an autosomal recessive disorder associated with a high risk of colorectal cancer. Since few studies have investigated the genotype–phenotype association in Japanese patients with MUTYH variants, the aim of this study was to clarify the clinicopathological findings in Japanese patients with MUTYH gene variants who were detected by screening causative genes associated with hereditary colorectal polyposis.

Methods

After obtaining informed consent, genetic testing was performed using target enrichment sequencing of 26 genes, including MUTYH.

Results

Of the 31 Japanese patients with suspected hereditary colorectal polyposis, eight MUTYH variants were detected in five patients. MUTYH hotspot variants known for Caucasians, namely p.G396D and p.Y179D, were not among the detected variants.Of five patients, two with biallelic MUTYH variants were diagnosed with MUTYH-associated polyposis, while two others had monoallelic MUTYH variants. One patient had the p.P18L and p.G25D variants on the same allele; however, supportive data for considering these two variants ‘pathogenic’ were lacking.

Conclusions

Two patients with biallelic MUTYH variants and two others with monoallelic MUTYH variants were identified among Japanese colorectal polyposis patients. Hotspot variants of the MUTYH gene for Caucasians were not hotspots for Japanese patients.

     

Differences in PD-L1 expression on tumor and immune cells between lung metastases and corresponding primary tumors

Background

It has been reported that the tumor microenvironment, including tumor-associated immune cells (ICs) and programmed cell death-ligand 1 (PD-L1) expression, differs between primary and metastatic tumors. This study aimed to elucidate the differences in PD-L1 expression on tumor cells (TCs) and ICs between lung metastases and corresponding primary tumors.

Superselective Transcatheter Arterial Embolization for Large Unruptured Renal Angiomyolipoma in Lymphangioleiomyomatosis

Purpose

To retrospectively evaluate therapeutic performance and complications of superselective transcatheter arterial embolization (TAE) for unruptured renal angiomyolipoma (AML) in patients with lymphangioleiomyomatosis (LAM) and to investigate the correlation between percentage reduction in tumor volume and intratumoral fat content.