Experimental columnar metaplasia in the canine oesophagus

Regeneration of canine oesophageal mucosa was studied under basal conditions and in the presence of gastro-oesophageal reflux. In normal circumstances mucosal defects in the oesophagus regenerate by squamous epithelium. In the presence of gastro-oesophageal reflux of either acid or a combination of acid and bile, regeneration was frequently by columnar epithelium (Barrett's oesophagus). This columnar regeneration was not seen with bile reflux alone. By the use of squamous barriers to proximal migration of columnar epithelium in the stomach, it was demonstrated that columnar re-epithelialization may occur from cells intrinsic to the oesophagus and is not dependent on proximal migration of cardiac columnar epithelium. The cell of origin of this epithelium may be located in oesophageal gland ducts and is likely to be a multipotential stem cell since the regenerated columnar epithelium may contain goblet and parietal cells not normally found in the oesophagus. This epithelium is morphologically distinct on mucin histochemistry from cardiac columnar epithelium. These findings support the concept that Barrett's epithelium is metaplastic.     

Barrett's ulcer

A case of an ulcer developing within previously documented Barrett's epithelium is reported. The patient had symptoms of gastroesophageal reflux for many years and Barrett's esophagus beginning 21 cm from the incisor teeth was documented by endoscopy one year earlier. Hospitalization was necessitated by an upper gastrointestinal bleed which was found to be due to an ulcer at 29 cm from the incisors. There was no inflammation of the surrounding columnar epithelium nor was there any esophagitis within the squamous epithelium. This case documents that ulcers in Barrett's esophagus can arise de novo within the columnar epithelium despite the hypothesis that this epithelium is present because it is more resistant to acid/peptic damage than squamous epithelium. This suggests that some ulcers in Barrett's epithelium may be due to spontaneous degeneration of the epithelium as this patient had no esophagitis, suggesting that gastroesophageal reflux was not causing diffuse damage.     

Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett's esophagus

A distinctive type of multilayered epithelium (ME) has been described at the neo-squamocolumnar junction and within columnar mucosa in patients with Barrett's esophagus (BE). This epithelium has morphologic and ultrastructural features of both squamous and columnar epithelium. Multilayered epithelium may represent an early or intermediate stage of columnar metaplasia; therefore, we performed this study to determine the morphologic and biologic characteristics of this epithelium and to gain insight into its derivation. Esophageal mucosal biopsies containing ME from 17 patients with BE were evaluated morphologically, stained with a variety of mucin histochemical stains; and also immunostained with antibodies against cytokeratins (CK) 13 (squamous epithelium marker); 14 (basal squamous epithelium marker) 7, 8/18, 19, and 20 (columnar epithelium markers), MIB-1 (proliferation marker); villin (intestinal brush border protein); and TGFalpha, EGFR, pS2, and hSP (enteric proliferation/differentiation regulatory peptides). The results were compared with normal esophageal squamous epithelium, normal gastric cardia epithelium, specialized-type intestinal epithelium (BE), and esophageal mucosal and submucosal gland duct epithelium. Multilayered epithelium expressed a pattern of mucin production (neutral mucin, sialomucin, and sulfomucin in 88%, 100%, and 71% of cases, respectively) and cytokeratin expression (CK 13 and 19 in the basal "squamoid" cells, CK 7, 8/18, 19, and 20 in the superficial "columnar" cells) similar to that of columnar epithelium in BE, and showed a high capacity for cellular proliferation (Ki-67-positive in 88% of cases) and differentiation (TGFalpha, EGFR, pS2 and villin-positive in 100%, 100%, 93%, and 66% of cases, respectively). The mucosal gland duct epithelium showed a similar phenotypic pattern and, in one case, was seen to give rise to ME at the surface of the mucosa. These data provide evidence in support of the hypothesis that ME represents an early or intermediate stage in the development of esophageal columnar metaplasia (BE). The mucosal gland duct epithelium may contain progenitor cells that can give rise to ME.     

The epithelium in the female urethra: a quantitative study

Histological sections were prepared from 8 regions along the length of the urethra in 16 women 19 to 82 years old. The epithelium was examined under the light microscope at 4 points in each region and the type of epithelium was classified. Our results indicate that the human female urethra is lined by stratified squamous, pseudostratified columnar and, occasionally, transitional epithelium. There is a gradual change from squamous to columnar epithelium with advancing age. More squamous epithelium is present at the distal end of the urethra.     

Experimental Barrett's esophagus and the origin of intestinal metaplasia

Many questions remain unanswered regarding the pathogenesis and the cell origin of Barrett's esophagus. Recent studies suggest that progenitor cell populations, which are presumed to reside at the basal layer in the squamous epithelium and at the esophageal glands duct epithelium, may differentiate into a glandular phenotype leading to the development of columnar epithelium in the distal esophagus. Other studies also support the hypothesis that cardiac epithelium may precede the occurrence of specialized intestinal metaplasia. It remains unclear whether cardiac-type epithelium in Barrett's esophagus arises from squamous epithelium or from migration of native cardiac epithelium at the EGJ into the distal esophagus. Experimental animal models of chronic reflux esophagitis, although with some shortcomings when researchers extrapolate the study data to the human situation, have provided interesting insights into possible mechanisms associated with the occurrence of Barrett's esophagus. A better understanding of the molecular mechanisms regulating the development of Barrett's esophagus is necessary for developing new strategies directed toward prevention and treatment of this metaplastic condition with a potential risk for malignant transformation.     

缺血再灌注小肠中DNA甲基化对细胞凋亡和增殖的调控

目的探讨缺血再灌注小肠中DNA甲基化对小肠细胞凋亡和增殖是否具有调控作用。方法将35只健康雄性Wistar大鼠随机分为正常组n=5）、假手术组n=5）及缺血再灌注（0、3、6、12、24h,n=5）组。利用脱氧核糖核苷酸末端转移酶介导的缺口末端标记测定法、透射电镜和免疫组织化学方法分别检测细胞凋亡和细胞增殖的变化,最后通过DNA甲基化位点组织末端酶链接检测法检测DNA甲基化。结果①与正常组和假手术组比较,缺血再灌注组缺血再灌注后3、6及12h时在小肠绒毛上皮、黏膜固有层及隐窝上皮中凋亡细胞均明显增加（P〈0．01）,且透射电镜检测证实,黏膜固有层的凋亡细胞主要是淋巴细胞和少量吞噬细胞。②与正常组和假手术组比较,缺血再灌注后3、6、12及24h时在小肠绒毛上皮中细胞增殖明显（P〈0．01）,缺血再灌注后6h和12h时在小肠黏膜固有层和隐窝上皮中细胞增殖明显（P〈0．01）。③正常组和假手术组DNA甲基化在小肠绒毛上皮和隐窝上皮部分有弱表达;在缺血再灌注组中,小肠隐窝上皮部分DNA甲基化在近小肠干细胞部位表达最强,从隐窝上皮到绒毛上皮是以从强到弱的趋势发生变化的。结论本研究的初步研究结果提示,缺血再灌注小肠中DNA甲基化可能对小肠细胞凋亡和增殖具有调控作用。     

The mucosal zones of the female urethra]

The short female urethra contains mucosal zones varying in extent. The proximal part, starting at the urinary bladder, is lined by a typical urothelium. It consists of several cell layers, which are covered by particularly large cells. After only a few millimeters this urothelium gives way to a stratified non-keratinized squamous epithelium containing abundant deposits of glycogen. Within this epithelium, islets varying in the extent of a stratified columnar epithelium they occupy are found. The squamous epithelium lines almost the whole length of the urethra up to its distal segment, changing shortly before the orificium externum urethrae to a stratified non-keratinized squamous epithelium which continues into the epithelium of the labia minora. This arrangement of the mucosal zones has been found in autopsy material from young women (25 and 29 years). In middle-aged women (41 and 43 years) the stratified non-keratinized squamous epithelium still predominates. In old women (84 and 90 years) only remnants of the stratified non-keratinized squamous epithelium are recognizable. Columnar epithelium lines the total length of the urethra. These results indicate that the structure of the female urethra depends on age and presumably also on the hormonal state of the mucosal zones.     

Bronchopulmonary foregut malformation

Bronchopulmonary foregut malformation (BPFM) is a rare anomaly of accessory pulmonary tissue that usually arises from esophagus or stomach. We present a case of extralobar pulmonary sequestration (ELS) connecting with the esophagus by a cyst, the inner wall of which is lined with squamous epithelium or respiratory epithelium. BPFM is sometimes used to group a number of ventral anomalies of accessory pulmonary tissue. The term currently refers specifically to those lesions composed of sequestrations that retain communication with the gastrointestinal tract. Usually the communication is a well-formed muscular tube lined with stratified squamous or columnar epithelium. The presence of both epithelia in a communication that is a component of the BPFM suggests embryogenesis. We describe an adult with BPFM composed of ELS and a connecting stalk to the esophagus by a foregut cyst that contains both squamous epithelium and respiratory epithelium.     

Squamous metaplasia of tracheal epithelium associated with high-volume, low pressure airway cuffs.

The tracheas of 12 patients, intubated from 2 hours to 20 days with tracheal airways equipped with the newer style, high-volume, low-pressure (HVLP) cuffs, were examined at autopsy. The type and severity of iatrogenic damage to the epithelium and submucosa was determined and compared to that seen in a previous study of 54 patients, who had been intubated with the older-style low-volume, high-pressure (LVHP) cuffed airways. The tracheal epithelial and submucosal damage due to intubation with the HVLP cuffed airways was considerably less than that with LVHP cuffs. The submucosal glands were often spared, and some of the tracheal epithelium even survived 20 days of exposure to the "soft" cuffs. However, the pseudostratified ciliated epithelium, which normally lines the trachea, was often replaced by stratified squamous epithelium. If such a zone of nonciliated epithelium remains in the trachea of a long-term survivor, its detrimental effect on the removal of particulate matter from the tracheobronchial tree may have to be considered.     

Benign polyps with prostatic-type epithelium of the urethra and the urinary bladder. A suggestion of histogenesis based on histologic and immunohistochemical studies

The clinicohistologic features of seven urethral and four urinary bladder polyps with prostatic-type epithelium are described. The average age of the patients was 50 years. Seven patients had prior cystoscopies and in none of them was the lesion noted initially. Histologically the lesions were papillary or polypoid and the surface was lined predominantly by prostatic-type epithelium with interspersed transitional epithelial cells or by transitional epithelium with interspersed prostatic-type epithelial cells. The prostatic-type columnar cells contained foamy, faintly eosinophilic cytoplasm, which stained strongly for prostate specific antigen and prostatic acid phosphatase. In all the lesions, there were prostatic acini in the underlying fibrovascular stroma, which was devoid of smooth muscle. The intermingling of prostatic-type cells and transitional epithelium, on the surface of the polyps, the absence of lesions at previous cystoscopies, the coexistence of cystitis cystica glandularis (a metaplastic lesion), and the older age group of our patients suggest that the prostatic-type epithelium in the polyps of urethra and urinary bladder is an acquired lesion, most likely a metaplastic response of transitional epithelium, which embryologically was multipotential.     

Concurrent pericardial diverticulum and unilocular thymic cyst lined with ciliated respiratory epithelium: a rare case report

Thymic cysts are divided into two groups as unilocular and multilocular cysts. Cystic wall is generally lined with squamous, transitional, cuboidal, or columnar epithelium. Unilocular cysts that are lined with ciliated respiratory epithelium are extremely rare, and there are only two reports in the literature. In this paper, we present a case, which had concurrent unilocular thymic cyst lined with ciliated respiratory epithelium and pericardial diverticulum.     

Distribution of lactoferrin in the normal and inflamed human prostate: an immunohistochemical study.

A polyclonal rabbit antibody to lactoferrin was used to localize the distribution of lactoferrin within the different zones of the normal human prostate as well as within the inflamed human prostate. Cases of normal central zone, peripheral zone, periurethral glandular tissue, as well as cases in which foci of moderate to severe inflammation, along with varying degrees of inflammation-related atrophy, were studied. In cases with inflammation, the staining pattern of lactoferrin was compared to the staining pattern of prostate-specific antigen. Within the central zone, lactoferrin staining occurred in numerous individual cells peppered throughout the epithelium as well as within multiple intraepithelial lumens (lacunae). These lacunae were often numerous enough to give the central zone epithelium a fenestrated appearance; they were not seen in any of the other regions of the prostate. With the exception of an occasional individual cell or isolated positive gland, normal peripheral zone exhibited very little lactoferrin activity. Staining within the transition zone was similar to that seen in the peripheral zone. Staining within the urethral lining of the epithelium in the periurethral glands showed a distinct pattern of frequent intense staining involving the entire gland; frequent individual positive cells were also often seen. Three patterns of staining were identified in prostatic inflammation. Mild periglandular chronic inflammation produced foci of epithelial lactoferrin positivity that coincided precisely with the areas of inflammation. Severe acute inflammation produced strong staining within luminal secretions while cytoplasmic staining was limited to the luminal surface of the epithelium. Post-inflammatory atrophy showed intense diffuse lactoferrin staining in the scant cytoplasm of the atrophic epithelium. In 12 of the 17 cases of inflammation that were studied, areas of post-inflammatory atrophy or severe inflammation commonly showed absence of prostate specific antigen staining and epithelium that was strongly lactoferrin-positive. Within the normal human prostate, lactoferrin appears to be produced primarily within the epithelium of the central zone, periurethral glands, and lining epithelium of the prostatic urethra. Lactoferrin-filled central zone lacunae appear to be structures unique to the central zone. The distribution of lactoferrin in the periurethral glands and urethral lining epithelium, along with the intense production of lactoferrin in the presence of inflammation, and the preservation of lactoferrin production in severe inflammation or atrophy suggest that lactoferrin may be a key component of the inflammatory response within the human prostate.     

In situ hybridization of prostate-specific antigen mRNA in human prostate.

Prostate-specific antigen (PSA) mRNA was detected by in situ hybridization utilizing a 428 base pair [35S]-labelled cDNA probe from the 3' noncoding region of the PSA gene. Thirty six fresh surgical specimens were collected from patients undergoing radical retropubic prostatectomy for carcinoma of the prostate. Quantitative analysis of the levels of PSA mRNA in both the benign and malignant tissues was performed using an IBAS 2000 Image Analysis System. The results of this study demonstrated that there is a significant decrease in the expression of PSA mRNA in the carcinoma tissue when compared to the benign epithelium. The average binding (number of silver grains/1 x 10(4) microns. 2) for 20 specimens of malignant epithelium was 475 +/- 161 and 586 +/- 140 for 16 specimens of benign epithelium (p less than 0.05). Eleven patients had both benign and malignant tissue from the same surgical specimen available for study. From these paired specimens, the PSA mRNA expression was also significantly reduced in the malignant epithelium when compared to the benign epithelium, 445 +/- 162 and 588 +/- 135 respectively (p less than 0.005). The PSA protein was detected using a monoclonal antibody to PSA with an immunohistochemical staining technique. The PSA protein expression paralleled the expression of the PSA mRNA in the majority of the tissue sections. Many of the tumor specimens showed a heterogeneous expression of PSA, whereas all of the benign epithelium had a uniform high level of PSA expression. In conclusion, PSA mRNA and protein are located only within the glandular epithelial tissue, the expression of PSA protein parallels that of the PSA mRNA, and both the PSA protein and PSA mRNA are significantly decreased in the malignant epithelium when compared to benign prostatic epithelium.     

组织工程角膜上皮移植抑制角膜碱烧伤新生血管形成的临床观察

目的：观察组织工程角膜上皮移植对角膜碱烧伤新生血管的抑制作用.方法：我院2005-2010年期间收治严重角膜碱烧伤（角膜缘干细胞缺陷）17例24眼,其中组织工程角膜上皮移植9例11眼,羊膜移植8例13眼.所有患者在手术前及手术后均行裂隙灯检查,观察角膜上皮、组织浸润、新生血管情况,对两组患者角膜新生血管情况进行评分和比较.结果：术后两组角膜新生血管评分均较手术前明显减少（P〈0.05）.在术后第21天,组织工程角膜上皮移植和羊膜移植组角膜新生血管评分分别为（1.410±0.765）分和（2.500±0.961）分,术后第60天分别为（1.770±0.832）分和（2.820±0.947）分.在术后两个评价时间点,组织工程角膜上皮移植组均较羊膜移植组角膜新生血管显著减少,两组间差异有显著性（P〈0.05）.组织工程角膜上皮移植组和羊膜移植组术后第60天新生血管评分均较术后第21天稍高,但差异均无显著性（P〉0.05）,表明两组角膜新生血管在移植3周后基本保持稳定.结论：组织工程角膜上皮移植对严重的角膜碱烧伤新生血管的抑制作用明显好于羊膜移植.     

Integrity of airway epithelium is essential against obliterative airway disease in transplanted rat tracheas.

BACKGROUND: The pathogenesis of obliterative bronchiolitis after lung transplantation requires further elucidation. In this study we used rat trachea transplantation to examine the role of epithelium in the progression of obliterative airway disease. METHODS: Normal and denuded (i.e., epithelium removed) trachea grafts from Lewis (LEW) and Brown Norway (BN) rats were transplanted sub-cutaneously into LEW rats. Viable trachea epithelial cells (to recover epithelium) were seeded into the lumen of some of the denuded tracheas. Grafts were removed at different time-points between 2 days and 8 weeks after transplantation. Histologic analysis was performed to evaluate cellular infiltration of inflammatory cells, loss of epithelium, and obliteration of trachea lumen. RESULTS: Obliteration was found to occur in trachea transplants after loss of epithelium, caused by rejection in allografts or by enzymatic denudation in isografts. In these situations, fibroblasts started to proliferate and migrate into the lumen in the second week after transplantation. Obliteration could be prevented when epithelial integrity was restored by seeding epithelial cells; no obliteration occurred when denuded trachea isografts were seeded with epithelial cells, whereas non-seeded denuded tracheas were obliterated at Day 6 after transplantation. CONCLUSIONS: We conclude that integrity of airway epithelium is essential for rat trachea transplants to be safeguarded from obliterative airway disease. For clinical lung transplantation the results of our study suggest that protection of the integrity of airway epithelium may be important in preventing the development of obliterative bronchiolitis.     

Histologic classification of patients based on mapping biopsies of the gastroesophageal junction

This study consists of 959 consecutive patients in whom endoscopic biopsies were taken according to a protocol that permitted mapping and measurement of epithelial types in the gastroesophageal region. The epithelial types were classified as normal (oxyntic and squamous) and questionably abnormal (oxyntocardiac, cardiac, intestinal) by strict histologic criteria. Patients were classified into four groups based on the length of histologically defined abnormal glandular epithelium in the measured biopsies. A total of 811 (84.6%) patients had 0 to 0.9 cm of questionably abnormal columnar epithelium between normal oxyntic mucosa and squamous epithelium. Of these, 161 (19.9%) patients had no abnormal epithelium, 158 (19.4%) patients had oxyntocardiac mucosa, 372 (45.9%) patients had cardiac mucosa, and 120 (14.8%) patients had intestinal metaplasia. A total of 148 (15.4%) patients had >or=1 cm of abnormal columnar epithelium. All but one patient in this group had cardiac or intestinal epithelia. The prevalence of intestinal epithelium increased progressively with increasing length of abnormal columnar epithelium, being present in 70.4% in the 1- to 2-cm group, 89.5% in the 3- to 4-cm group, and 100% with in the >or=5 cm group. We propose a histologic grading system of biopsies based on these findings.     

Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling

The thymidine labeling index (TLI) was measured in vitro in the epithelium and stroma of benign prostate glands and seminal vesicles and in the epithelium of prostatic adenocarcinomas. The mean epithelial TLI of normal peripheral (posterior) prostatic zone was 0.12 per cent, and that of the normal central (deep) zone was 0.11 per cent. Mean normal stromal TLI's were 0.08 per cent and 0.06 per cent, respectively. The mean TLI of epithelium in nodular hyperplasia was 0.31 per cent, which differs significantly from normal epithelium (p less than 0.05), and the mean stromal TLI was also increased (0.16 per cent, p less than 0.1). The mean TLI of prostatic adenocarcinomas was 0.90 per cent (range 0.14 to 3.90 per cent) which was significantly higher than for either normal epithelium (p less than 0.001) or epithelium of nodular hyperplasia (p less than 0.05). Trends of increasing TLI with increasing histologic grades and increasing nuclear size and numbers of nucleoli were not significant. The data support participation of both epithelial and stromal proliferation in nodular hyperplasia, and indicate a low basal proliferative rate in normal prostatic glands. The low TLI's of prostatic adenocarcinomas relative to other malignancies are consistent with their frequently slowly progressive course. The very low proliferative rate of seminal vesicular epithelium (mean TLI 0.02 per cent) may account for the rarity of seminal vesicular carcinomas.     

Immunohistochemical localization of estrogen-specific 17β-hydroxysteroid oxidoreductase in the human and mouse prostate

The estrogen-specific 17β-hydroxysteroid oxidoreductase (17β-HSOR) enzyme protein was stained immunohistochemically in the newborn and adult human prostate as well as in the mouse prostate. In the newborn human prostate, ductal and urethral epithelia were faintly stained, whereas in the adult human prostate, intense staining for 17β-HSOR enzyme antigen could be detected in the epithelium of the collecting ducts and urethral epithelium as well as in the epithelium of the intraprostatic vas deferens and seminal vesicle epithelium. Immunostaining was weak in the prostatic tissues of both newborn and adult prostate. No positive cells were found in stroma. The activity of NADPH-dependent ³H-estrone reductase was detectable in cell-free homogenates prepared from human prostatic tissues. The activities showed a good correlation with immunocytochemical findings. In the mouse, neonatal estrogenization resulted in intensively stained epithelium of the collecting ducts at the age of 14 days. Moreover, when adult control and neonatally estrogenized mice were implanted with 17β-estradiol, the metaplastic epithelium of the periurethral collecting ducts of neonatally estrogenized mice was intensively stained with 17β-HSOR. These findings suggest that metaplastic epithelium rises from 17β-HSOR-positive cells. The similar distributions of 17β-HSOR-positive cells confirm the concept of homology in the posterior estrogen-responsive periurethral region (containing the periurethral ducts and periurethral glands) of the mouse and humans. Our findings further suggest that the 17β-HSOR-positive cells may have the same origin and hormonal control in both species. © 1994 Wiley-Liss, Inc.