Sonographic classification of testicular tumors by tissue harmonic imaging: experience of 58 cases

Purpose

To evaluate the relationship between our proposed sonographic classification of testicular tumors by tissue harmonic imaging and histological type.

Methods

We retrospectively analyzed 58 testicular tumors and tumor-like lesions [seminomatous germ cell tumor (SGCT): 28; non-seminomatous germ cell tumor (NSGCT): 16; lymphoid and hematopoietic tumor (LHT): 7; Leydig cell tumor: 1; epidermal cyst: 2; and tumor of paratesticular structure (TPS): 4]. We divided a sonographic image into six types for morphological criteria and three types for color Doppler criteria. We examined the relationship between the sonographic classification and histological type.

Results

For morphological criteria, there were 21 cases of Type I (36%), 15 Type II (26%), 9 Type III (15%), five Type IV (9%), five Type V (9%), and three Type VI (5%). For color Doppler criteria, there were 47 cases classified as hypervascular (81%), eight as hypovascular (14%), and three as avascular (5%). Most of the SGCTs were divided into types I and II; the NSGCTs into types III, IV, and V; the LHTs into only type II; and the TPSs into type VI.

Conclusion

We established a sonographic classification of testicular tumors with various histological types. This sonographic classification is potentially useful for estimating the histological type of testicular tumors.

     

Grades of 43 fish species in Japan based on IgE-binding activity.

BACKGROUND: Hypersensitivity reactions to fish are a common food allergy, but IgE-binding activity to fish species have not been fully elucidated. The aim of this study was to identify fish with high binding activity to IgE in sera from Japanese fish-hypersensitive individuals. METHODS: 38 children with a history of at least one episode of hypersensitivity after ingestion of fish were enrolled and 34 children with no history of reactions and negative IgE results for at least five kinds of fish antigen were included as controls. Using a radioallergosorbent test, we examined IgE-binding to each fish species using sera from fish-hypersensitive subjects. Fish were then graded according to IgE-binding activity. RESULTS: Many fish species, including red salmon, silver salmon, yellowfin tuna, big eyed tuna, Atlantic tuna, saurel, skipper, yellowtail, Japanese sardine, bonita and mackerel had high IgE-binding activity. All of these fish are abundantly consumed in Japan. The hypersensitivity reactions experienced by many subjects occurred after ingestion of species with high IgE-binding activity. Only halibut (Osteichthyes) and sharks (Chondrichthyes) had low IgE-binding activity. CONCLUSIONS: A correlation was observed between IgE levels and expression of symptoms after fish ingestion. High consumption of salmon, tuna, scad (including saurel), skipper, yellowtail, sardine, bonita and mackerel in Japan might be the cause of the high IgE-binding activity of these species. The grades of fish species consumed widely in Japan are likely to be useful for nutritional instruction of fish-allergic patients.     

CCL2 is critical for immunosuppression to promote cancer metastasis

We previously found that cancer metastasis is accelerated by immunosuppression during Snail-induced epithelial-to-mesenchymal transition (EMT). However, the molecular mechanism still remained unclear. Here, we demonstrate that CCL2 is a critical determinant for both tumor metastasis and immunosuppression induced by Snail⁺ tumor cells. CCL2 is significantly upregulated in various human tumor cells accompanied by Snail expression induced by snail transduction or TGFβ treatment. The Snail⁺ tumor-derived CCL2 amplifies EMT events in other cells including Snail^? tumor cells and epithelial cells within tumor microenvironment. CCL2 secondarily induces Lipocalin 2 (LCN2) in the Snail⁺ tumor cells in an autocrine manner. CCL2 and LCN2 cooperatively generate immunoregulatory dendritic cells (DCreg) having suppressive activity accompanied by lowered expression of costimulatory molecules such as HLA-DR but increased expression of immunosuppressive molecules such as PD-L1 in human PBMCs. The CCL2/LCN2-induced DCreg cells subsequently induce immunosuppressive CD4⁺FOXP3⁺ Treg cells, and finally impair tumor-specific CTL induction. In murine established tumor model, however, CCL2 blockade utilizing the specific siRNA or neutralizing mAb significantly inhibits Snail⁺ tumor growth and metastasis following systemic induction of anti-tumor immune responses in host. These results suggest that CCL2 is more than a chemoattractant factor that is the significant effector molecule responsible for immune evasion of Snail⁺ tumor cells. CCL2 would be an attractive target for treatment to eliminate cancer cells via amelioration of tumor metastasis and immunosuppression.     

A novel stop-gain CUL3 mutation in a Japanese patient with autism spectrum disorder

BackgroundCUL3 encodes cullin-3, a core component of a ubiquitin E3 ligase. CUL3 mutations have recently been associated with autism spectrum disorder (ASD); however, the detailed clinical courses have been described in only a limited number of patients with CUL3 mutations and neurodevelopmental diseases, including ASD.Case reportA 21-month-old Japanese girl presented with febrile status epilepticus and thereafter exhibited developmental regression, including loss of her verbal ability, eye contact, and skills in activities of daily living. Trio-based exome sequencing identified a de novo two-base insertion in CUL3, c.1758_1759insTG, p.(Thr587*).ConclusionWe report a case of a patient with ASD and a stop-gain CUL3 variant. Screening of CUL3 variants is worth considering for patients with ASD, especially those with Rett-like developmental regression.     

Clinical and neuroendocrinological characteristics of delayed orthostatic hypotension in Parkinson’s disease

Clinical Autonomic Research - Delayed orthostatic hypotension (DOH), a fall in blood pressure after a 3-min cutoff, is clinically meaningful. The aim of this study was to elucidate the clinical and...     

Rapid turnover of the W chromosome in geographical populations of wild silkmoths, Samia cynthia ssp.

Our previous studies revealed a considerably high level of chromosomal polymorphism in wild silkmoths, Samia cynthia ssp. (Lepidoptera: Saturniidae). Geographical populations of this species complex differ in chromosome numbers and show derived sex chromosome systems including Z0/ZZ in S. cynthia ricini (2n?=?27/28; Vietnam), neo-Wneo-Z/neo-Zneo-Z in S. cynthia walkeri (2n?=?26/26; Sapporo, Hokkaido) and neo-WZ₁Z₂/Z₁Z₁Z₂Z₂ in S. cynthia subsp. indet. (2n?=?25/26; Nagano, Honshu). In this study, we collected specimens of S. cynthia pryeri in Japanese islands Kyushu, Shikoku and Honshu, with an ancestral-like karyotype of 2n?=?28 in both sexes and a WZ/ZZ sex chromosome system, except for one population, in which females have lost the W chromosome. However, the S. cynthia pryeri W chromosome showed a very unusual morphology: It was composed of a highly heterochromatic body, which remained condensed throughout the whole cell cycle and of a euchromatin-like “tail.” We examined molecular composition of the W and neo-W chromosomes in S. cynthia subspecies by comparative genomic hybridisation and fluorescence in situ hybridisation with W chromosome painting probes prepared from laser-microdissected W chromatin of S. cynthia pryeri. These methods revealed that the molecular composition of highly heterochromatic part of the S. cynthia pryeri W chromosome is very different and lacks homology in the genomes of other subspecies, whereas the euchromatin-like part of the W chromosome corresponds to a heterochromatic part of the neo-W chromosomes in S. cynthia walkeri and S. cynthia subsp. indet. Our findings suggest that the curious WZ system of S. cynthia pryeri may represent an ancestral state of the Samia species complex but do not exclude an alternative hypothesis of its derived origin.     

Control of renal uric acid excretion and gout

PURPOSE OF REVIEW: Impaired renal uric acid excretion is the major mechanism of hyperuricemia in patients with primary gout. This review highlights recent advances in the knowledge of normal mechanisms of renal uric acid handling and derangement of these mechanisms in uric acid underexcretion. RECENT FINDINGS: The discovery of URAT1 has facilitated identification of other molecules potentially involved in uric acid transport in the renal tubules. Some of these molecules show gender differential expression in animal experiments. Sodium-dependent monocarboxylate cotransporters have been shown to transport lactate and butyrate, and may have roles in hyperuricemia associated with diabetic ketoacidosis and alcohol ingestion. Certain polymorphisms in SLC22A12 may be associated with the development of hyperuricemia or gout, although confirmation is needed. Mechanisms of hyperuricemia associated with uric acid underexcretion in patients with familial juvenile hyperuricemic nephropathy also remain to be clarified. Distal tubular salt wasting and compensatory upregulation of the resorption of sodium and uric acid in the proximal tubule may explain the hyperuricemia associated with this disorder. SUMMARY: Much progress has been made in understanding the mechanisms of renal uric acid handling. Elucidation of the mechanisms of hyperuricemia in patients with familial juvenile hyperuricemic nephropathy will shed light on the function of uromodulin, functional impairment of which eventually results in diminished uric acid excretion.     

SNARE mediates autophagosome–lysosome fusion

Autophagy is an intracellular bulk degradation/recycling system that turns over cellular constituents. This system has also been shown to play a crucial role in host defense, termed antimicrobial autophagy (xenophagy), in which it functions to degrade intracellular foreign microbial invaders. Xenophagosomes undergo a stepwise maturation process that consists of fusion with lysosomes, after which the cargo undergoes degradation. We have previously shown that intracellular group A Streptococcus (GAS) is captured by xenophagosomes termed GAS-containing autophagosome-like vacuoles (GcAVs), where GAS organisms are degraded following fusion with lysosomes. Our recent investigations have shown that endocytic soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are involved in the fusion of xenophagosomes and lysosomes. Confocal microscopic analysis has shown that SNAREs, including VAMP8 and Vti1b, colocalize with GFP-LC3 in GcAVs. Our findings also suggested that Vti1b is derived from autophagic compartments, whereas VAMP8 originates from lysosomes. Knockdown of the combinational SNARE proteins VAMP8 and Vti1b with siRNAs disturbed the autophagic fusion of xenophagosomes with lysosomes, and cellular bactericidal efficiency significantly diminished. Furthermore, knockdown of these SNAREs inhibited the fusion of canonical autophagosomes with lysosomes. These findings strongly suggest that a combinatorial SNARE complex with VAMP8 and Vti1b mediates the fusion of antimicrobial and canonical autophagosomes with lysosomes, an essential event for autophagic degradation.