人膀胱不同区域Cajal样间质细胞的分布及意义

目的观察人膀胱不同区域Cajal样间质细胞（interstitial cells of cajal,ICCs）的分布情况,探讨其作为起搏细胞在人膀胱的分布意义。方法标本来源于5个膀胱癌患者手术（全膀胱切除术）切下的正常非癌变膀胱全层组织（病理检查无病变）,按解剖学分组（顶部、体部、颈部）及组织学分组（黏膜层、黏膜下层、肌层）制作冰冻切片,运用免疫荧光显色技术观察ICCs的分布情况。结果通过激光共聚焦显微镜观察到在人膀胱不同区域发现的ICCs形态学、免疫表型与在消化道发现的ICCs类似。可见CD117呈阳性的ICCs出现在膀胱不同解剖区域及组织层次中,荧光主要在细胞膜及突起着色,细胞呈梭形,轴向两端存在突起。解剖学组中ICCs存在于膀胱顶部最多,膀胱体部次之,膀胱颈部罕见。组织学组中ICCs主要存在于肌层和黏膜下层,黏膜层少见。结论为临床上治疗某些疾病提供新的理论依据,ICCs在人膀胱顶部和肌层大量存在,很可能构成了膀胱活动的第一起搏点,使慢波向膀胱体、膀胱颈传播,缺乏及丧失ICCs可能会导致人类膀胱动力障碍性疾病。     

Alterations in smooth muscle contractile and cytoskeleton proteins and interstitial cells of Cajal in megacystis microcolon intestinal hypoperistalsis syndrome

Background/Purpose: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is characterized by decreased or absent peristalsis. Gastrointestinal motility depends on the enteric nervous system, smooth muscle cells (SMCs), and the interstitial cells of Cajal (ICCs). Contractile and cytoskeleton proteinase are important structural and functional components of SMCs. The aim of study was to examine the expression of contractile and cytoskeleton proteins in SMCs and distribution of ICCs in MMIHS bowel. Methods: Full-thickness bowel specimens were obtained from 4 infants with MMIHS and 4 controls. Specimens were processed as whole-mount preparations and frozen and paraffin sections. Combined staining of NADPH-d histochemistry/c-kit immunohistochemistry, single and double immunohistochemistry using [alpha ]-smooth muscle actin ([alpha ]-SMA), calponin (CALP), caldesmon (CALD), desmin (DES), protein gene product 9.5 (PGP 9.5) and c-kit antibodies were performed and examined using light and confocal scanning microscopy. Results: [alpha ]-SMA, CALP, CALD, and DES immunoreactivity were reduced markedly in MMIHS bowel compared with controls. Combined NADPH/c-kit staining showed dense network of ICCs around myenteric plexus in MMIHS bowel. In contrast, the intramuscular ICCs either were absent or reduced in MMIHS bowel. Conclusions: Marked reduction of contractile and cytoskeleton proteins in SMCs combined with reduced expression of intramuscular ICCs in the gut may be responsible for the motility dysfunction in MMIHS. J Pedriatr Surg 38:749-755. [copy ] 2003 Elsevier Inc. All rights reserved.     

Immunolocalization of the gap junction protein Connexin43 in the interstitial cells of Cajal in the normal and Hirschsprung's disease bowel

BACKGROUND: Interstitial cells of Cajal (ICC) are pacemaker cells between gastrointestinal smooth muscles; they generate spontaneous slow waves of the smooth muscle layers and mediate neurotransmission. The cellular network of ICC is connected by Gap junctions to each other and to the smooth muscle cells. Although there have been several studies reporting distribution of ICC in the normal bowel and pathological conditions such as Hirschsprung's disease, there is little information on the crucial role of Gap junctions in the intercellular communication in the gut musculature. The aim of this study was to investigate the immunolocalization of the Gap junction protein Connexin43 in the normal and Hirschsprung's disease (HD) bowel using whole-mount preparation technique and confocal laser scanning microscopy. METHODS: Full-thickness bowel specimens were collected at pull-through operation from 8 patients diagnosed as having HD. Normal control large bowel specimens were collected from 12 patients during bladder augmentation operation. Whole-mount preparation was performed on all specimens and double immunostaining was carried out using anti c-kit and antiConnexin43 antibodies. The immunolocalization was detected with the help of confocal laser scanning microscopy. RESULTS: Connexin43 immunoreactivity appeared in and between the c-kit-positive cells and along the smooth muscle fibers of the normal bowel and ganglionic part of HD bowel. In the aganglionic part of HD bowel there was no expression of Connexin43. In the transitional zone of HD the Connexin43 staining was weak and colocalized only in the processes of the c-kit-positive Cajal cells. CONCLUSIONS: Results of this study show for the first time that Gap junctional protein Connexin43 is present in the ICCs, which form a 3-dimensional network in the normal bowel wall. The lack of expression of Connexin43 in the aganglionic bowel and reduced expression in the transitional zone of HD suggest that the impaired intercellular communication between ICCs and smooth muscle cells may partly be responsible for the motility dysfunction in HD.     

Increased expression of endothelin B receptors in the diabetic rabbit urinary bladder: functional relevance

OBJECTIVES: To determine the effect of diabetes mellitus on the density and distribution of endothelin A (ETA ) and endothelin B (ETB ) receptor subtypes in the rabbit urinary bladder, and to assess the in vitro functional properties of endothelin-1 (ET-1) receptors in bladder smooth muscle strips from diabetic and healthy rabbits. MATERIALS AND METHODS: Diabetes mellitus was induced in six male New Zealand White rabbits with alloxan and their urinary bladders excised 6 months after the induction of diabetes. On serial detrusor and bladder neck sections, low- and high-resolution autoradiography was performed using radioligands for ET-1, ETA and ETB receptors; these sections were then analysed densitometrically. The results were compared with those from six age-matched healthy control rabbits. Functional responses were investigated using isometric tension studies. RESULTS: ETA and ETB receptor binding sites were localized to both the urothelium and smooth muscle of the detrusor and bladder neck. There were significantly more ETB receptor binding sites in the diabetic detrusor and bladder neck sections than in controls. ET-1 smooth muscle contractile responses were ETA receptor-mediated. The smooth muscle contractile responses to ET-1 were unaltered in the detrusor, but significantly impaired in the bladder neck of diabetic animals compared with controls. CONCLUSION: Alteration in the expression of ETB receptors and in vitro contractile smooth muscle responses to ET-1 in the diabetic rabbit urinary bladder neck may play a role in the pathophysiology of diabetic cystopathy.     

Immunohistochemical evidence of vanilloid receptor 1 in normal human urinary bladder

PURPOSE: Experimental and clinical evidences have shown the importance of the vanilloid receptor 1 (TRPV1) in the lower urinary tract. In humans, this receptor has been detected in nerve endings of primary sensory neurons, smooth muscle and connective tissue cells and in the rat also in the urothelium. The aim of this study is to identify, by immunohistochemistry, the cell types expressing TRPV1 in the human urinary bladder. MATERIAL AND METHODS: Specimens, obtained from normal urinary bladder by multiple biopsy and from ureter at the time of radical nefrectomy for renal cell carcinoma, were fixed and frozen. Full-thickness sections were processed for light and fluorescence microscopes. To label the TRPV1, three polyclonal antibodies were used: the anti-capsaicin receptor, the anti-VR1 (N-15) and the anti-VR1 (C-15). RESULTS: Urothelium, smooth muscle cells, mast cells and endothelium were labelled and the labelling was intracytoplasmatic. In the urothelial cells, the labelling was slightly granular. In the bladder urothelium, the superficial cells were more intensely stained than the basal and club-shaped cells. VR1-positive nerve fibers were seen running single and/or in groups in the sub-urothelium and as single varicose fibers in the muscle coat, and VR1-positive nerve endings in the urothelium. CONCLUSION: The present findings provide the evidence of the presence of TRPV1 on normal human urothelium where it could have important implications in the mechanism of action of intravesical vanilloids (capsaicin and resiniferatoxin).     

机械牵张对豚鼠膀胱组织Cajal间质细胞形态学及兴奋性的影响

目的 探讨机械牵张对豚鼠膀胱组织Cajal间质细胞(ICC)形态及兴奋性的影响.方法 建立雌性豚鼠膀胱颈部分梗阻(PBOO)模型作为实验组.并设假手术组作为对照.术后4周取膀胱组织制片,免疫荧光染色观察2组ICC形态和分布情况;胶原酶消化豚鼠膀胱制细胞悬液,免疫荧光标记,流式细胞仪检测2组c-kit阳性细胞比率.在弹性硅胶膜七原代培养膀胱ICC,利用Fluo-4钙荧光指示剂检测机械牵张对ICC钙信号的影响.结果 2组豚鼠膀胱组织铺片均可见c-kit染色阳性典型长梭形有突起的ICC,主要分布于平滑肌肌束间;PBOO组膀胱平滑肌间质增厚,c-kit染色阳性细胞数量及其突起明显增多,互相连接呈网络状;PBOO组c-kit阳性细胞比率为(6.7±1.7)%,显著高于对照组的(1.0±0.5)%,差异有统计学意义(P＜0.05).体外培养的ICC可检测到自发性钙波,机械牵张刺激可诱导ICC发生钙波增强现象.结论 机械牵张可诱导膀胱ICC兴奋性增强;PBOO膀胱组织中ICC数量及相互联系显著增多.ICC可能参与了膀胱牵张感受功能并在长期牵张应力负荷下发生一定的适应性改变.     

Immunocolocalization of the heme oxygenase-2 and interstitial cells of Cajal in normal and aganglionic colon

Purpose: Interstitial cells of Cajal (ICCs) are pacemaker cells that play an important role in the control of gut motility. Carbon monoxide (CO) has been proposed as an endogenous messenger molecule between ICC and smooth muscle cells in the gastrointestinal tract (GIT). Heme oxygenase-2 (HO-2) is the main physiologic mechanism for generating CO in human cells. The aim of this study was to investigate the immunocolocalization of the HO-2 and ICCs in normal and aganglionic bowel of Hirschsprung's disease (HD). Methods: Full-thickness specimens were obtained from aganglionic colon during pull-through operation from 10 patients diagnosed as having HD. Normal control large bowel specimens were collected from 4 patients during bladder augmentation procedures. Double immunostaining was carried out using c-kit and HO-2 antibodies. Immunolocalization was detected by means of confocal laser scanning microscopy. Results: HO-2 immunoreactivity (IR) was found in many ICCs present around the myenteric plexus, within the longitudinal and circular muscle layers and at the innermost part of the circular muscle layer in normal colon. In the aganglionic colon there was absence of HO-2 IR in the sparsely found ICCs. In the transitional zone of HD bowel the colocalization of HO-2 IR and ICCs was much reduced compared with controls. Conclusions: The results of this study provide the first evidence for the presence of HO-2 immunoreactivity in the ICCs in normal human colon and absence of HO-2 immunoreactivity in sparsely appearing ICCs in the bowel of HD patients. The lack of HO-2 in the ICCs in the bowel of HD patients may result in impaired intracellular communication between ICCs and SMCs causing motility dysfunction. J Pediatr Surg 38:73-77.     

Morphological aspects of the female pig bladder neck and urethra: quantitative analysis using computer assisted 3-dimensional reconstructions

PURPOSE: To investigate whether the pig is a suitable model for studies of lower urinary tract function and dysfunction, we sought to determine the morphology of the female pig bladder neck and urethra. Computer assisted 3-dimensional (D) reconstructions from step serial histological sections were used for visualization of the spatial relationships between neighboring urethral wall components, and the quantification of these components in the bladder neck and along the urethra. MATERIALS AND METHODS: Step serial histological paraffin sections from the bladder neck and urethra of 6 female pigs, stained with Masson's trichrome, were used to generate computer assisted 3-D reconstructions using MacStereology (Ranfurly MicroSystems Ltd., Airdrie, United Kingdom) as the 3-D software package. RESULTS: The bladder neck and urethral anatomy revealed well defined smooth and striated muscle layers that varied in location, regional distribution and orientation. Circular smooth muscle was maximally developed in the mid urethra, at which point maximal urethral pressure was observed. The longitudinal smooth muscle layer appeared continuous with the detrusor, implicating a possible role in urethral shortening at the onset of voiding. A small circular and longitudinal striated muscle component was present in the distal urethra. CONCLUSIONS: Anatomical differences exist between the female pig and human bladder neck and urethra, which were successfully highlighted using computer assisted 3-D reconstructions from step serial histological paraffin sections.     

Cajal-like cells in the human upper urinary tract

PURPOSE: Interstitial cells of Cajal (ICCs) have an important role in the regulation of gut motility as they are responsible for the slow wave activity of smooth muscle. It is still unknown if ICCs also occur in the human upper urinary tract. Since these cells express and are marked by the c-kit receptor CD117, we investigated its occurrence and distribution along the human upper urinary tract. MATERIALS AND METHODS: Tissues from 56 human ureters, spanning proximal, middle and distal ureter segments, were analyzed by indirect immunohistochemistry using the alkaline phosphatase-anti-alkaline phosphatase method and double labeling immunofluorescence on consecutive tissue sections. Several monoclonal and polyclonal antibodies to c-kit receptor were used in combination with various cell markers for histiocytic, mast cell, endothelial, epithelial, neuronal, smooth muscle and stem cell differentiation. RESULTS: The c-kit receptor was found in 3 cell types of the ureter and in round or spindle-shaped cells. Due to their antigenic profile the first one was revealed as mast cells occurring in all layers of the ureteral wall except the urothelium. In contrast, the population of spindle-shaped cells was only marked by c-kit receptor, thus, resembling ICCs. These ICC-like cells were found among the inner and outer smooth muscle layers, and in the lamina propria. They showed a slight decrease from proximal to distal ureteral segments. However, unlike intestinal ICCs their cytomorphology differed and some cells, representing the third group of c-kit receptor positive cells, were found within the urothelium. CONCLUSIONS: Our data demonstrate the presence of ICC-like cells and their ubiquitous distribution in the human ureter. The physiological importance and pathological significance of these findings must be evaluated by functional studies and investigations of certain pathological with urinary outflow disturbance conditions.     

Effect of anoxia-glucopenia and re-superfusion on intrinsic nerves of mammalian detrusor smooth muscle: importance of glucose metabolism

AIMS: To investigate the effect of anoxia/glucopenia and re-superfusion on intrinsic nerves in the mammalian urinary bladder. METHODS: Strips of detrusor smooth muscle were dissected from monkey and human urinary bladder and mounted for tension recording in organ baths superfused with Krebs solution. Human, monkey, and guinea-pig urinary bladders were treated to evaluate glycogen contents by a biochemical method. RESULTS: Detrusor strips from both monkeys and humans had to be exposed to anoxia-glucopenia for up to 2-2.5 hr to observe a progressive decline in the response to electrical field stimulation (EFS) of the intrinsic nerves, at variance with guinea-pig detrusor strips. In contrast, the response to direct activation of the smooth muscle with carbachol remained almost unaltered. Incubation of human and monkey detrusor strips with 2-deoxyglucose (2-DG) during 1 hr anoxia-glucopenia, however, caused a marked damage to the intrinsic nerves. The glycogen contents of both human detrusor specimens and monkey urinary bladders were 2.0- and 1.4-fold higher, respectively, than that found in guinea-pig urinary bladder; furthermore, untreated monkey detrusor sections showed a greater number of glycogen granules as compared to those subjected to anoxia-glucopenia and re-superfusion. In guinea-pig and in monkey detrusor sections glycogen granules were found in smooth muscle cells but not in neurons of intramural ganglia. CONCLUSIONS: A higher susceptibility of guinea-pig as compared to monkey and human nerves has been demonstrated; it is suggested that anaerobic glucose metabolism during anoxia-glucopenia is crucial for the functional recovery of detrusor intrinsic nerves from damage caused by anoxia-glucopenia and re-superfusion.     

膀胱平滑肌细胞与膀胱脱细胞基质的生物相容性研究

目的:研究膀胱平滑肌细胞与膀胱脱细胞基质(BAM)的生物相容性。方法:分离培养兔膀胱平滑肌细胞,采用α-平滑肌肌动蛋白(α-SMA)抗体进行鉴定。将以1×10 5个/mL的单细胞悬液均匀接种于制备BAM支架上,通过与单独培养的膀胱平滑肌细胞作对照,绘制两组细胞生长曲线图,对比观察两条生长曲线的差异性。 ...     

Function of M3 muscarinic receptors in the rat urinary bladder following partial outlet obstruction

PURPOSE: Partial outlet obstruction of the rat urinary bladder leads to hypertrophy and alteration in contractility of the detrusor muscle involving changes in muscarinic receptors. m3 muscarinic receptor subtype has been known to play a predominant role in contractility of normal urinary bladder. The purpose of the present study was to assess the role of m3 receptors in contractility of the obstructed bladder. MATERIALS AND METHODS: In male rats, partial outlet obstruction of the urinary bladder was performed by surgically tying a 6-0 suture around the bladder neck, reducing the diameter of it by 2/3 of the original size. Four weeks after the surgery, the bladders were removed and thin strips were microdissected. Similarly, bladder strips from age matched unoperated normal rats were obtained. Sets of four strips from four normal or four obstructed rats were mounted in an in vitro multi-muscle chamber containing normal physiological solution at 37C. The tension responses evoked by optimal electrical field stimulation at 1, 10, 30, 50, and 100 Hz, and the contracture responses evoked by 120 mM potassium and 0.01 to 300.0 microM carbachol were recorded using a Nicolet digital oscilloscope. Similar responses were recorded in different sets of four strips following exposure to 10 and 100 nM 4-DAMP, which is a muscarinic antagonist with a high affinity for m3 and m1 receptor subtypes. RESULTS: The obstructed bladders showed 119% increase in weight. In control physiological solution, the obstructed bladder strips did not show significant difference in electrically-evoked tension or carbachol contractures, but showed significantly lower potassium contractures compared with normal bladder strips. 4-DAMP at 10 to 100 nM significantly reduced the electrically evoked tension responses by about the same degree in normal and obstructed bladders, without affecting the potassium contractures. It significantly increased the EC50 values for carbachol contractures in normal bladder, and to a significantly lesser extent in obstructed bladder. Schild plots using the Hill transformed EC50 values showed that the pA2 value for 4-DAMP was not significantly different in normal and obstructed bladders. CONCLUSIONS: Significantly smaller potassium contracture in the obstructed bladder indicates that depolarizability of the detrusor muscle membrane, and consequently the activity of voltage-gated Ca2+ channels may be reduced in the detrusor after partial outlet obstruction. Lack of a significant difference in the effect of 4-DAMP on the electrically evoked tension responses and in the pA2 values for 4-DAMP assessed by carbachol contractures, in normal and obstructed bladder strips, indicates that m3 muscarinic receptors still play a predominant role in causing detrusor contractility in the obstructed bladder, as in the normal bladder.     

大鼠膀胱ICC样细胞与逼尿肌神经调控关系的形态学研究

目的 从形态学上探讨膀胱ICC样细胞在逼尿肌神经调控中的作用.方法 采用透射电镜观察大鼠膀胱内ICC样细胞、神经和逼尿肌细胞之间的超微结构关系.通过c-kit免疫荧光染色对大鼠膀胱ICC样细胞进行鉴定,并通过c-kit与PGP9.5免疫荧光双标观察ICC样细胞与神经的结构关系.结果 透射电镜显示,ICC样细胞与逼尿肌细胞紧密相邻处可见典型缝隙连接.在局部区域可见ICC样细胞的突起与神经末梢联系紧密.c-kit免疫荧光染色显示,大鼠膀胱内ICC样细胞主要位于黏膜下层、肌束边缘以及肌细胞间.c-kit与PGP9.5免疫荧光双标显示ICC样细胞与神经末梢在结构上关系紧密.结论 从形态学上看,膀胱内ICC样细胞具备参与逼尿肌神经调控的结构基础,进一步从功能学上予以证实将有助于全面阐明逼尿肌神经调控理论.     

Cajal样间质细胞在豚鼠膀胱肌层的分布及意义

目的研究豚鼠膀胱Cajal样间质细胞的分布、超微结构特点并探讨其功能。方法选择健康豚鼠10只,利用激光共聚焦显微镜和透射电镜观察膀胱Cajal样间质细胞在肌层的分布和结构特点。结果豚鼠膀胱肌层Cajal样间质细胞形成网状和平行状两种不同的分布。超微结构核大、具有丰富的细胞器。结论膀胱Cajal样间质细胞分布和超微结构与胃肠道的ICCs相似,具有起搏细胞特征。     

The distribution of interstitial cells of Cajal in congenital ureteropelvic junction obstruction

Purpose

The authors analysed the distribution of c-kit-positive interstitial cells of Cajal (ICCs) in obstructed ureteropelvic junction (UPJ) and its age-related changes.

Methods

Twenty specimens were obtained from children with intrinsic ureteropelvic junction obstruction (UPJO), at the average age of 8.1 years (8 months–16.8 years), fixed in formalin and embedded in paraffin. Five control samples were taken from children at the average age of 2.3 years (2.4 months–7.4 years). All specimens were analysed by the immunohistochemistry test with light microscopy with respect to c-kit expression. The distribution of c-kit-positive ICCs in the two groups was compared and the correlation between the distribution of c-kit-positive ICCs and the patients’ age in UPJO cases was analysed. The results were examined by Yates’ χ² test, Mann–Whitney U test, and t test for Pearson’s correlation coefficient. A P value < 0.05 was considered as statistically significant.

Results

No statistically significant differences were found in the distribution of c-kit-positive ICCs between UPJO and the control group. No correlation was established between the age of patients with UPJO and the distribution of c-kit-positive ICCs.

Conclusion

No distributional difference found in obstructed and unobstructed UPJ seems to indicate that UPJO is not associated with anomalous distribution of c-kit-positive ICCs. Age-related changes in the expression of c-kit-positive ICCs are equally distributed in obstructed UPJ.     

Abnormalities of C-Kit-positive cellular network in isolated hypoganglionosis

Background/Purpose: C-Kit-positive interstitial cells of Cajal (ICCs) have a key role in the normal motility function and development of the bowel. They are pacemaker cells, which facilitate active propagation of electrical events and neurotransmission in the bowel wall. ICCs are present in the bowel as myenteric ICCs (ICC_myS) and muscular ICCs (ICC_musS). The aim of this study was to examine the distribution of c-Kit-positive ICCs and their relationship to the autonomic intrinsic innervation in bowel specimens from patients with isolated hypoganglionosis. Methods: Full-thickness large bowel specimens were obtained from 6 patients with hypoganglionosis and from 4 patients during bladder augmentation (controls). Frozen sections and whole-mount preparations were stained using c-Kit immunohistochemistry, nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, and acetylcholinesterase (AChE) histochemistry and evaluated using normal brightfield and confocal laser scanning microscopy. Results: NADPH-diaphorase and AChE histochemistry findings showed characteristic histologic features of hypoganglionosis, eg, sparse and small myenteric ganglia and low or absent AChE activity in the lamina propria. Myenteric plexus in the normal bowel was surrounded by a dense network of c-Kit-positive ICC_myS, whereas in hypoganglionosis sparse isolated ICC_myS were found. C-Kit-positive ICC_musS were reduced markedly in the longitudinal and circular muscle layer and at the innermost part of the circular muscle in hypoganglionosis. Conclusion: Deficient expression of c-Kit-positive myenteric and muscular ICCs in the hypoganglionic colon may contribute to the motility dysfunction in the affected bowel.     

Altered Expression of Interstitial Cells of Cajal in Congenital Ureteropelvic Junction Obstruction

PurposePeristaltic contractions in the upper urinary tract serve to move urine from the kidney through the ureter to the bladder. Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis in children. To our knowledge the pathophysiology of UPJ obstruction is unknown. C-kit positive interstitial cells of Cajal (ICCs) are pacemaker cells that facilitate active propagation of electrical events and mediate neurotransmission. We investigated the expression of c-kit positive cells in the muscle layer of normal and obstructed UPJ specimens.Materials and MethodsA total of 19 human formalin fixed, paraffin embedded specimens of intrinsic UPJ obstruction from children with a mean age of 2.3 years (range 2 months to 12 years) and 7 control samples from children with a mean age of 4.5 years (range 11 months to 9 years) were investigated immunohistochemically for the expression of c-Kit oncoprotein and peripherin by light and laser scanning microscopy. Quantification of immunolabeled structures was quantified using computerized image analysis.ResultsPeripherin immunoreactivity was strong in the muscle layer of normal UPJ specimens, while in UPJ obstructed specimens there was a decrease in peripherin positive nerve fibers. In normal UPJ specimens there were many c-Kit positive ICCs between the muscle bundles. The density of ICCs was markedly decreased in the muscle layers of UPJ obstructed specimens.ConclusionsTo our knowledge this study shows for the first time the immuno-expression of c-Kit positive ICCs in the proximal part of the normal human upper ureter. The altered density of c-Kit positive cells in UPJ obstruction may have a role in the failure of transmission of peristaltic waves across the UPJ.     

A study of dysplasia associated with bladder cancer--histopathological findings of bladder giant sections and related urinary cytology

Giant sections were prepared from 31 totally removed bladders because of transitional cell carcinoma and examined for accompanied urothelial dysplasia. Preoperatory urinary cytology related to dysplasia was also investigated. Dysplasia of the urinary bladder was morphologically defined as the urothelium with intermediate atypism between normal transitional epithelium and carcinoma in situ (CIS) of grade 3 anaplasia. Dysplasia was divided into four groups from two points of view: slight and severe dysplasia on the basis of cellular anaplasia, epithelial stratification and cellular polarity, and clear cell and compact cell dysplasia on the basis of features of dysplastic cell cytoplasm. Compact cell slight dysplasia was recognized in all specimens examined. Compact cell severe dysplasia as well as CIS was frequently accompanied with high grade papillary and non-papillary cancers, but not with low grade papillary cancer. Both slight and severe clear cell dysplasia tended to be frequently associated with high grade cancer. Because of no distinctiveness in nuclear atypia from CIS, severe dysplasia could be regarded as so called CIS of grade 2 anaplasia. From the current results, it appears likely that severe dysplasia is related to the occurrence of high grade bladder cancer. In addition, dysplastic cells exfoliated in to urine retained features of each type of original dysplasia, which were identified with a more than 70% accuracy. The result indicates that urinary cytology offers histologic aspects of coexisting dysplasia as well as bladder cancer.