Bizarre leiomyoma of the scrotum

Scrotal leiomyomas with atypical bizarre nuclei are rare, which might be misdiagnosed as malignant tumor. We describe a case of scrotal bizarre leiomyoma in a 65-yr-old man. The tumor was a 1 cm-sized, well circumscribed, oval mass arising from the tunica dartos muscle. Histologically, it was formed by whorling bundles of fusiform cells with occasional atypical, pleomorphic nuclei and pseudo-inclusions. Mitosis was not found. Although morphologically atypical, scrotal bizarre leiomyomas take on a biologic behavior not different from that of conventional leiomyoma, they should be distinguished from leiomyosarcoma to avoid unnecessary treatment.     

Galactosylated PVDF membrane promotes hepatocyte attachment and functional maintenance

One of the major challenges in BLAD design is to develop functional substrates suitable for hepatocyte attachment and functional maintenance. In the present study, we designed a poly(vinylidene difluoride) (PVDF) surface coated with galactose-tethered Pluronic polymer. The galactose-derived Pluronic F68 (F68-Gal) was adsorbed on PVDF membrane through hydrophobic-hydrophobic interaction between PVDF and the polypropylene oxide segment in Pluronic. The galactose density on the modified PVDF surface increased with the concentration of the F68-Gal solution, reaching 15.4 nmol galactosyl groups per cm2 when a 1 mg/ml of F68-Gal solution was used. The adsorbed F68-Gal remained relatively stable in culture medium. Rat hepatocytes attachment efficiency on F68-Gal modified PVDF membrane was similar to that on collagen-coated surface. The attached hepatocytes on PVDF/F68-Gal membrane self-assembled into multi-cellular spheroids after 1 day of culture. These attached hepatocytes in spheroids exhibited higher cell functions such as albumin synthesis and P450 1A1 detoxification function compared to unmodified PVDF membrane and collagen-coated surface. These results suggest the potential of this galactose-immobilized PVDF membrane as a suitable substrate for hepatocyte culture.     

Miscibility and Intermolecular Specific Interactions in Blends of Poly(hydroxyether sulfone) and Poly(N‐vinylpyrrolidone)

Summary: The blends of poly(hydroxyether sulfone) (PHES) with poly(N‐vinylpyrrolidone) (PVPy) were investigated by means of differential scanning calorimetry (DSC) and FTIR spectroscopy. The miscibility of the blend system was established on the basis of the thermal analysis results. DSC showed that the PHES/PVPy blends prepared by casting from N,N‐dimethylformamide (DMF) possessed single, composition‐dependent glass transition temperatures, indicating that the blends are miscible in the entire composition. The experimental glass transition temperatures have higher values than those calculated on the basis of additive behavior; the variation of the glass transition temperatures of the blends was accounted for by the Kwei equation. FTIR studies indicate that competitive hydrogen bonding interactions exist upon addition of PVPy to the system, which were involved in the self‐ and cross‐association, i.e., ? OH···O?S, ? OH···OH of PHES and ? OH···O?C< of PVPy. The FTIR spectra in the range of the sulfonyl stretching vibrations showed that the hydroxyl‐associated sulfonyl groups are partially “set free” upon addition of PVPy to the system. The IR spectroscopic investigation of both the model compounds and the PHES/PVPy blends suggests that the strength of the hydrogen bonding interactions in the blend system increases in the following order: ? OH···O?S, ? OH···OH and ? OH···O?C<.

Plot of glass transition temperature for PHES/PVPy blends as a function of weight fraction of PVPy. The prediction of the Kwei equation yields the values of k = 1 and q = 122.     

Changes of interleukin expression correlate with Helicobacter pylori infection and lymph node metastases in gastric carcinoma.

Helicobacter pylori (HP) infection induces expression of IL-8 and IL-10 in benign gastric epithelium. This study compared the expression of cytokines in CD4+ and CD8+ lymphocyte subsets of peripheral blood lymphocytes (PBL), benign mucosal lymphocytes (ML), and tumor infiltrative lymphocytes (TIL) as well as in the benign and malignant epithelial cells of the same patient, with respect to the presence of HP infection, lymph node metastases, and tumor histologic type. The mRNA of the cytokines was measured by a semiquantitative RT-PCR method. The levels were ranked and compared using the Wilcoxon sign-ranked test. Compared with CD8+ ML, the CD8+ TIL expresses higher levels of IL-6 and IL-8 but lower level of IL-4 in patients with lymph node metastases. In patients with HP infection, expression of IL-8 and IL-10 was higher in the gastric carcinoma cells than in the benign epithelial cells while expression of IL-6 and IL-8 were higher in CD8+ TIL than CD8+ ML. Overexpression of IL-8 in HP associated gastric carcinomas suggested that they might have arisen from HP-infected epithelial cells.     

Brachydactyly type A3 is caused by a novel 13 bp HOXD13 frameshift deletion in a Chinese family

Brachydactyly type A (BDA) is defined as short middle phalanges of the affected digits and is subdivided into four types (BDA1‐4). To date, the molecular cause is unknown. However, there is some evidence that pathogenic variants of HOXD13 could be associated with BDA3 and BDA4. Here, we report a Chinese autosomal dominant BDA3 pedigree with a novel HOXD13 mutation. The affected individuals presented with an obviously shorter fifth middle phalanx. The radial side of the middle phalanx was shorter than the ulnar side, and the terminal phalanx of the fifth finger inclined radially and formed classical clinodactyly. Interestingly, the index finger was normal. The initial diagnosis was BDA3. However, the distal third and fourth middle phalanges were also slightly affected, resulting in mild radial clinodactyly. Both feet showed shortening of the middle phalanges, which were fused to the distal phalanges of the second to the fifth toes, as reported in BDA4. Therefore, this pedigree had combined BDA3 and atypical BDA4. By direct sequencing, a 13 bp deletion within exon 1 of HOXD13 (NM_000523.4: c.708_720del13; NP_000514.2: p.Gly237fs) was identified. The 13 bp deletion resulted in a frameshift and premature termination of HOXD13. This study provides further evidences that variants in HOXD13 cause BDA3‐BDA4 phenotypes.     

Aberrant T cell responses to myelin antigens during clinical exacerbation in patients with multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease of presumed T cell autoimmunity against self myelin. We hypothesized that if myelin-reactive T cells are associated with the disease processes, they may undergo activation and expansion during acute exacerbation. In this study, we examined the precursor frequency, epitope recognition and cytokine profile of myelin-reactive T cells in 14 relapsing/remitting MS patients during exacerbation and remission. The study revealed that T cells recognizing the immunodominant peptides of candidate myelin antigens, including myelin basic protein (MBP), proteolipid protein and myelin oligodendrocyte glycoprotein, occurred at increased precursor frequency during acute exacerbation. The T cell responses to MBP focused on the immunodominant regions (residues 83-99 and 151-170) during exacerbation and shifted toward other epitopes of MBP at the time of remission. Furthermore, there was a marked increase in the production of T(h)1 cytokines among T cell lines obtained during exacerbation compared to those obtained during remission. The study demonstrated that myelin-reactive T cells underwent selective activation and expansion during acute MS exacerbation. In contrast, myelin-reactive T cells found during remission in the same patients generally resembled those identified in healthy controls with some discrepancies. The findings suggest potential association of aberrant myelin-reactive T cell responses with acute exacerbation in MS, which may reflect transient activation of myelin-reactive T cell populations of pathogenic potential.     

Myoblasts fail to stimulate T cells but induce tolerance

Recent interest in myoblast transfer and in the use of myoblastsas vehicles in gene therapy has made it important to understandthe potential immunogenicity of allogeneic or neoantlgen-expresslngmyoblasts. Given the problems of producing a pure populationof myoblasts, In this study we used a tumour-derived musclecell line (TE671), with phenotyplc features of myoblasts, whichwe transfected to express HLA-DR1. However, this cell line wasunable to stimulate either established HLA-DR1-specific alloreactlveT cell clones or a primary alloresponse. Nor could it presenthaemagglutlnln peptide HA 306–324 to DR1-restricted, HA306–324-speciflc T cell clones or lines. Indeed, prelncubatlonwith DR1-expressing TE671 and HA 306–324 rendered suchT cells tolerant as Judged by their subsequent inability toproliferate in response to a DR1⁺ B cell line plus peptide HA306–324. These results imply that myoblasts do not providecostlmulatory signals, and are therefore unlikely to stimulateallospeclfic T cells following myoblasts transplantation orto initiate neoantlgen-speclfic immune responses following Invivo transfection.     

The role of beta-catenin, TGF beta 3, NGF2, FGF2, IGFR2, and BMP4 in the pathogenesis of mesenteric sclerosis and angiopathy in midgut carcinoids

A subset of midgut carcinoids (MCs) result in mesenteric angiopathy (MA) and bowel infarction as a consequence of vascular compression caused by extensive mesenteric sclerosis (MS). The goal of this study was to determine whether the level of expression of several fibrosing-related growth factors was related to the finding of MA and/or MS in MCs. Eighteen cases of MC, 6 with both extensive MS and MA (group I), 5 with extensive MS only (group II), and 7 with ordinary MS only (group III), were analyzed for immunoexpression of beta-catenin, transforming growth factor-beta 2 (TGF beta 2), nerve growth factor 2 (NGF2), fibroblast growth factor 2 (FGF2), insulin growth factor receptor (IGFR), and bone morphogenic protein 4 (BMP4) in formalin-fixed, paraffin-embedded sections. Standard immunohistochemical technique was used following antigen retrieval. Immunostaining was scored semiquantitively as the product of the percentage and intensity (0 to 2+) of the immunostaining, giving a possible range of 0 to 200. One-way analysis of variance and Mann-Whitney nonparametric analyses were used for statistical analysis. The mean scores of immunoreactivity of each factor in groups I, II, and III were as follows: 135, 174, and 147 for beta-catenin (cytoplasmic reactivity only); 106, 112, and 92 for TGF beta 3; 1.67, 32, and 36 for NGF-2; 2.5, 48, and 55 for FGF-2; 19, 112, and 66 for IGFR2; 140, 45, and 52 for BMP4. There were significant differences in NGF-2 immunoreactivity between groups I and III (P = 0.0023) and in BMP4 immunoreactivity between groups I and II (P = 0.017) and groups I and III (P = 0.022). All MCs expressed high levels of membranous beta-catenin, moderate levels of TGF beta 3 and IGFR2, and low levels of FGF-2, with no significant differences seen among the groups. MCs with prominent MS and MA (group I) expressed significantly higher BMP4 than those in groups II and III, suggesting a potential role of BMP4 in the pathogenesis of MA. The level of NGF-2 expression was significantly lower in group I than in group III, possibly indicating abnormal angiogenesis in the formation of angiopathy.