Histologic Classification of Endoscopically Removed Flat Colorectal Polyps: A Multicentric Study

A total of 594 flat colorectal polyps, removed at endoscopy, were histologically classified into non-neoplastic (n=49) and neoplastic (n=545) polyps. Non-neoplastic polyps were subdivided into metaplastic (n=45) and hyperplastic (n=4), whereas neoplastic polyps were subdivided into adenomas (n=481), intramucosal carcinomas (n=28) and invasive adenocarcinomas (n=36). Several adenoma phenotypes were discerned: tubular (n=375), serrated (n=59), villous (n=39), mixed (n=7) and fenestrated (n=1). Intramucosal carcinomas were subdivided into tubular (n=26) and serrated (n=2), and invasive adenocarcinomas into tubular (n=32), serrated (n=3) and fenestrated (n=1). The microscopic characteristics of each histologic phenotype described in this communication are defined and illustrated.     

Characterization of the specific meningeal T cell response to intracerebral inoculation of Theiler's murine encephalomyelitis virus

The presence of a resident T lymphocyte population in the meninges of normal SJL/J mice has been detected by the use of the T cell-specific mitogen concanavalin A. Optimal conditions for [3H]thymidine incorporation were studied. An antigen-specific meningeal T cell proliferative response in SJL/J mice, primed by intracerebral inoculation of Theiler's murine encephalomyelitis virus, was also detected. This response indicated that leptomeningeal mononuclear cell infiltrations are involved in the immune response that triggers the demyelinating disease.     

Musculo-fibrous anomaly in Barrett's mucosa with dysplasia

We investigated the histological alterations occurring in the muscularis mucosae, the lamina propria mucosae, and the submucosa in areas adjacent to invasive adenocarcinoma in 32 resected esophagi with Barrett's mucosa. In 26 of the 32 specimens, we observed a thickening of the muscularis mucosae, with overgrowth of the muscle fibers into the lamina propria mucosae. In other areas, collagen-rich fibrotic tissue replaced the muscularis mucosae, the lamina propria mucosae, and even the submucosa. In 31 of the 32 specimens, we noted cystic dilatations of the esophageal glands. Normal esophageal glands and cystically dilated glands with dysplastic lining were often surrounded, compressed, and deformed by the fibrotic tissue. The compression of the glandular outlets by the collagen-rich tissue or by proliferating dysplastic cells appeared to be the two main factors in the histogenesis of these cysts. This may result in difficulty in differentiating, in biopsy specimens, between normal and dysplastic esophageal glands "trapped" in the collagen-rich fibrotic tissue and true invasive adenocarcinoma in the Barrett's mucosa.     

A model to evaluate acute and chronic stress in the colonic mucosa of rats

The effect of acute and chronic stress on the colonic mucosa of the rat was investigated at various time intervals, ranging from one day to eight weeks. The amount of DNA synthesized by the mucosa was used as a marker of time-related events. A total of 75 Sprague-Dawley rats were investigated. Acute stress was considered for rats briefly plunged (psychic stimulus) or swimming for two hours (physical stimulus). Chronic stress was determined when rats were briefly plunged or swam for two hours for periods ranging from one to eight weeks. "Sham-transported" rats were used as controls. DNA in the descending colon decreased significantly in rats swimming for two weeks, but increased (even for plunged rats) at four and eight weeks. In the ascending colon, a substantial increase in DNA content was found in rats plunged or swimming for eight weeks. The descending colon appears to be quantitatively more affected by various stressors than the ascending colon. It is apparent that, in control rats, the mucosa of the descending colon differs from the ascending colon. Fluctuations in the colonic DNA synthesis throughout the experiment suggest that this phenomenon may be connected to compensatory mechanisms toward cell adaptation to stress conditions. The model may prove of value in studies of the therapeutic abrogation of the fluctuations of the DNA replication of the colonic mucosa during the acute and chronic phases of a given stress.     

川芎嗪诱导大鼠骨髓间质干细胞分化为神经元样细胞的研究

目的用川芎嗪(ligustrazin hydrochloride)在体外定向诱导SD青年鼠骨髓间质干细胞(mesenchymal stem cells，rMSCs)分化为神经元样细胞。方法用低糖DMEM冲洗骨髓腔，收集骨髓细胞悬液，接种在塑料培养瓶中。经体外扩增、纯化，选用第5代后的骨髓间质干细胞进行诱导分化。用10μg／LbFcF预诱导24h，更换成含川芎嗪的无血清培养基DMEM诱导间质干细胞分化为神经元样细胞。用免疫组织化学SABC法鉴定神经丝蛋白(NF—M)、神经元特异性烯醇化酶(NSE)、巢蛋白(nestin)、微管联合蛋白-2(MAP-2)、生长相关蛋白-43(GAP-43)、胶质纤维酸性蛋白(GFAP)的表达。结果第5代间质干细胞形态达到均一，呈梭形。用川芎嗪诱导15min到3h，间质干细胞胞体逐渐增大，并伸出细长突起形似神经元样细胞。免疫组织化学显示NF-M、NSE、nestin、MAP-2和GAP-43表达阳性，而GFAP阴性。对照组上述染色均为阴性。结论川芎嗪可诱导骨髓间质干细胞分化为神经元样细胞。     

Further studies on the musculo-fibrous anomaly of the Barrett's mucosa in esophageal carcinomas.

A total of 50 esophagi with carcinoma were reviewed for the presence of histological changes in the subepithelial tissues of the Barrett's mucosa. Those changes consisted in the thickening of the muscularis mucosae, the presence of muscle fibres in the lamina propria mucosae, fibrosis of the submucosa and sometimes total obliteration of the subepithelial tissues by collagen-rich sclerosis. Those changes have been connoted as "musculo-fibrous anomaly". Barrett's mucosa was present in all 18 specimens with adenocarcinoma and in 13 of the remaining 32 specimens with squamous cell carcinoma. Musculo-fibrous anomaly of the Barrett's mucosa occurred in all 18 specimens with adenocarcinoma and in 10 of the 13 specimens with a concomitantly growing squamous cell carcinoma. Esophageal and metaplastic glands were surrounded, compressed and deformed by the fibrotic tissue. The histological changes described explain the difficulties in the differential diagnosis--in biopsy specimens--between normal glands or glands with dysplastic changes "trapped" in the collagen-rich fibrotic tissue and true invasive adenocarcinoma of the Barrett's esophagus.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

The Turner syndrome research registry: Creating equipoise between investigators and participants

To address knowledge gaps about Turner syndrome (TS) associated disease mechanisms, the Turner Syndrome Society of the United States created the Turner Syndrome Research Registry (TSRR), a patient‐powered registry for girls and women with TS. More than 600 participants, parents or guardians completed a 33‐item foundational survey that included questions about demographics, medical conditions, psychological conditions, sexuality, hormonal therapy, patient and provider knowledge about TS, and patient satisfaction. The TSRR platform is engineered to allow individuals living with rare conditions and investigators to work side‐by‐side. The purpose of this article is to introduce the concept, architecture, and currently available content of the TSRR, in anticipation of inviting proposals to utilize registry resources.     

Pregnancies after intracytoplasmic sperm injection with cryopreserved testicular spermatozoa

In 25 patients (14 suffering from obstructive azoospermia, sixfrom non-obstructive azoospermia, three from astheno-azoospermiaand two from absence of ejaculation) spermatozoa were extractedfrom testicular biopsies. Intracytoplasmic sperm injection (ICSI)with fresh testicular spermatozoa was performed in 18 cases;spermatozoa in excess were cryopreserved in pills. No pregnancieswere achieved. In the remaining seven patients, testicular spermatozoawere retrieved and cryopreserved during a diagnostic testicularbiopsy. After thawing, sperm motility was assessed in 17 cases(68%), and 18 ICSI with cryopreserved testicular spermatozoawere performed. The mean two-pronuclear (2PN) fertilizationrate was 59%, the mean cleavage rate was 92%, and six clinicalpregnancies were achieved, all of them still ongoing (pregnancyrate 33%). A comparison of the results of ICSI carried out withfresh or cryopreserved testicular spermatozoa showed that themean 2PN fertilization rates per cycle (53 compared with 55%),mean cleavage rates per cycle (99 compared with 96%) and embryoquality were not significantly different In conclusion, cryopreservationof testicular spermatozoa is feasible, even in patients withnon-obstructive azoospermia, and the results of ICSI with frozen-thawedtesticular spermatozoa are similar to those obtained using freshtesticular spermatozoa. Cryopreservation of testicular spermatozoamay avoid repetition of testicular biopsies to retrieve spermatozoafor successive ICSI cycles in patients in whom the only sourceof motile spermatozoa is the testicle.