- Silica Granuloma after Intermittent Intramuscular Injections: A Case Report.
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Suk Jin Choi, Jong Im Lee, Jung Ran Kim, Tae Jung Jang, Ki Kwon Kim, Phil Hyun Chung
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Korean J Pathol. 2003;37(5):369-372.
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- Most silica-contaminated wounds of the skin heal without complications. Cutaneous silica granuloma is a poorly understood, uncommon condition resembling a sarcoidosis. We report a case of silica granuloma after intermittent intramuscular injections. A 70-year-old man presented a painless mass in his right buttock for 2 weeks. He had received intermittent intramuscular injections of antihistamine drugs due to chronic dermatitis for 30 years.
The histolopathological findings showed numerous hyalinized collagenous nodules with concentric layers, and an ill-defined chronic granulomatous inflammation containing foreign material. A polarized light microscopic examination revealed birefrigent particles. The presence of silica components was confirmed by scanning electron microscopy and energy dispersive X-ray microanalysis.
- Expression of Cyclin D1, Cyclin E, p21Cip1 and p27Kip1 in Chemically Induced Rat Mammary Tumor Treated with Tamoxifen and Transforming Growth Factor-1.
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Tae Jung Jang, Jae Hum Park, Mee Yon Cho, Ki Kwon Kim, Jung Ran Kim
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Korean J Pathol. 2001;35(2):151-157.
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- BACKGROUND
Tamoxifen (TAM) inhibits the action of estrogen by binding to estrogen receptors, and also has non-estrogen receptor mediated cytostatic activities. Transforming growth factor-1 (TGF-1) inhibits the proliferation of many other cell types, such as epithelial, hematopoietic and endothelial cells.
METHODS
We investigated the effects of tamoxifen on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors and the expression of cyclin D1, cyclin E, p21Cip1, and p27Kip1 by performing immunohistochemistry and Western blot analysis, and studied whether TGF-1 injection amplified the effects of TAM. When tumor size reached between 10-15 mm in the largest dimension, the rats were divided into 3 groups: DMBA-control group (n=12), DMBA-TAM group (n=14) and DMBA-TAM plus TGF-1 group (n=5).
RESULTS
The consecutive administration of TAM markedly decreased the tumor development compared with the DMBA-control group. The DMBA-TAM and DMBA-TAM plus TGF-1 groups showed decreased expression of bromodexoyuridine, cyclin D1, cyclin E, and p21Cip1 when compared with those of the DMBA-control group. On the other hand, the labeling index of p27Kip1 was higher in the DMBA-TAM plus TGF-1 group than in the DMBA-control group.
CONCLUSION
TAM suppresses tumor development, which may be associated with down-expression of cyclin D1 and cyclin E, and overexpression of p27Kip1, and addition of TGF-1 does not influence tumor development treated by TAM.
- Expression of p16 and Rb in 9,10-Dimethyl-1,2-Benzanthracene Induced Rat Ovarian Carcinogenesis.
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Ki Kwon Kim, Dong Hun Kim
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Korean J Pathol. 2001;35(2):144-150.
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- BACKGROUND
In order to investigate the roles of p16 and Rb, their expression was evaluated in 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced ovarian cancers of rats.
METHODS
DMBA-coated silk was inserted into both ovaries of 20 9-week-old Sprague-Dawley rats. The experimental period lasted 20 weeks. The tumor histology was classified and the expression of p16 and Rb in the ovarian tumors was analyzed by immunohistochemistry and Western blot.
RESULTS
The p16 and Rb labeling index was significantly lower in the ovarian cancers than the normal ovarian surface epithelium of a rat. There were no differences among the cancer types. In Western blot analysis, the expressions of p16 and Rb in ovarian cancers were lower than those in normal ovarian tissue. No correlation was present between p16 and Rb.
CONCLUSION
The abnormal expression of p16 and Rb occurs in DMBA-induced rat ovarian cancer and might be involved in carcinogenesis.
- Histopathologic Change and Apoptotic Profile in Basal Ganglia of Rat Induced by Manganese Administration.
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Chang Won Ha, Jong Im Lee, Jung Ran Kim, Tae Jung Jang, Ki Kwon Kim, Dong Hoon Kim
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Korean J Pathol. 2000;34(6):419-430.
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- Mn (manganese) is known to induce Parkinsonian neurological disorder. Several lines of evidence suggest that apoptosis is involved not only in physiological cell death during normal development but also in neurodegenerative disease. The mechanism of Mn induced cell death remains poorly understood. In the present study, we evaluated the morphologic changes and apoptotic profile in basal ganglia using rat model of Mn toxicity. The rats were divided into three groups: the first group was a control; the second group was subdivided by administration dosage of Mn into group A (5, 10 mg MnC12/ kg) and group B (20, 40 mg MnC12/kg). The rats of each subgroup received a injection of Mn via tail vein every week for 4 weeks. The second group received 4 repeated injection of 10 mg MnC12/kg in the same manner and the rats were sacrificed at day 1, 3 & 7 in group I and at day 10, 21, 42, and 90 in group II after the last injection. A significant loss of neuron and gliosis were observed in the basal ganglia in the experimental groups (p<0.05), which were more pronounced in group II than in the control or group I. No significant difference in number of nerve cells or degree of gliosis was identified in the substantia nigra. Apoptotic cells were also increased in basal ganglia of experimental groups and appeared among neurons (10%), glial cells (10%), and endothelial cells (60%). Apoptotic figures were consistently noted through the entire experimental period after Mn injection in basal ganglia. In conclusion, these results demonstrate that Mn-induced cytopathic insult affects various cell types in basal ganglia and shows variable sensitivity in the different regions of brain, especially in the apoptotic cell death of the neuron. The overaccumulation of Mn in the brain might be attributed from the breakdown of blood-brain barrier due to the injury through the apoptosis.
- Expression of p27Kip1 Protein in Carcinoma of the Urinary Bladder.
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Ki Kwon Kim, Jung Ran Kim
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Korean J Pathol. 2000;34(5):341-348.
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- The cyclin-dependent kinase (cdk) inhibitor p27Kip1 gene is a powerful molecular determinant of cell cycle progression. Loss of expression of p27Kip1 has recently been shown to be predictive of disease progression in several human malignancies. The prognostic value and expression of p27Kip1 have been incompletely studied in bladder cancer. In this study, we investigated the relationship between p27Kip1 protein expression and clinicopathologic parameters in 50 cases of carcinoma of the urinary bladder by conducting immunohistochemical analysis and DNA flow-cytometry. Malignant bladder tissue demonstrated a heterogeneous pattern of p27Kip1 immunoreactivity. In addition, there was progressive loss of expression with increasing tumor grade. The expression of p27Kip1 protein was unrelated to stage, DNA ploidy and S phase fraction (SPF). SPF was unrelated with tumor grade and DNA ploidy.
The results indicate that p27Kip1 is frequently expressed in well differentiated transitional cell carcinomas of the urinary bladder but less often expressed in muscle-invasive transitional cell carcinomas. The expression of p27Kip1 and its prevalence in low-grade tumors may reflect growth regulatory influences and potential inhibiting action in tumor progression and novel predictive markers of the biological potential of bladder tumors.
- Manganese Intoxication in the Rat A neuropathologic study and distribution of manganese in rat brain.
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Tae Jung Jang, Jung Ran Kim, Jong Im Lee, Dong Hoon Kim, Ki Kwon Kim, Ji Yong Kim, Hae Kwan Cheong, Hyun Sul Lim
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Korean J Pathol. 1999;33(9):662-674.
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- We investigated a topographical distribution of managanese, and immunohistochemical density of tyrosine hydroxylase (TH), and histopathologic findings in globus pallidus and substantia nigra according to manganese dose and time course in the brain of rats which received MnCl2 intravenously.
Topographical distribution of manganese was also investigated after injection of FeCl2.
The manganese concentrations of brain in control and experimental group were highest in pituitary gland and thalamus, and lowest in the cerebral cortex. The manganese concentration of blood was increased proportionally to the dose administered, and the biological half-life of blood manganese was between 21 and 42 days. The manganese concentrations of brain were increased proportionally to the dose, and increase rate was highest in olfactory bulb, and the biological half-lives of brain manganese ranged from 42 days to 90 or more days; the longest were observed in pituitary gland, medulla oblongata and cerebral cortex. In case of administration of FeCl2, the manganese concentrations of brain were higher than that of control group in dose of 2.5 mg/kg, and decreased proportionally to the administered dose, resulting in lower level compared with control group in high dose of FeCl2 administered. Significantly decreased number of nerve cell and increased gliosis in globus pallidus were observed in experimental group, which were closely correlated with the duration after manganese injection, but no significant change of number of nerve cell expressing TH and gliosis were observed in substantia nigra.
Density of immunohistochemical reaction for TH in globus pallidus made little difference between control and experimental group. These results suggest that pathology of manganese intoxication is caused by the loss of nerve cells in globus pallidus, and closely correlated with the duration after manganese exposure.
- Imprint Cytologic Features of Fibroadenoma of the Breast with Extensive Infarction: A Case Report .
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Suk Jin Choi, Jong Im Lee, Jung Ran Kim, Tae Jung Jang, Ki Kwon Kim, Dong Hoon Kim, Byoung Ook Jeoung
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Korean J Cytopathol. 1999;10(2):169-174.
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- Spontaneous Infarction of fibroadenoma of the breast is very uncommon and may lead to difficulties in clinical and pathological diagnosis. Most reported cases occured in young women during pregnancy or lactation. This report describes imprint cytologic features of an infarcted fibroadenoma in a 19-year-old young woman without evidence of pregnancy. The smears revealed many individually scattered degenerated or necrotic epithelial or spindle stromal cells and naked nuclei on dirty necrotic background. A few sheets of cohesive uniform epithelial cells and a few fragments of stromal cells were also present. Most of the epithelial cells had pyknotic and hyperchromatic nuclei, however, cellular atypism such as pleomorphism, prominent nucleoli or mitosis were not present. Though the necrotic ductular and glandular outline of this case may bear a superficial resemblance to adenocarcinoma, obvious cytologic atypia or mitosis, even in the necrotic areas, were not present.
- Castration-induced Apoptosis in the Rat Prostate.
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Ki Kwon Kim, Sang Sook Lee
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Korean J Pathol. 1998;32(6):431-442.
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- This study was carried out to investigate the morphologic findings and process of castration-induced apoptosis in the rat prostate. The experimental group was treated with bilateral orchiectomy followed by sequential sacrifices at 1, 2, 3, 4, 5, 6, 7 days and 2, 3 weeks (6 rats, respectively). Ventral prostate was extirpated and examined by light microscopic and immunohistochemical, ultrastructural observation. Apoptotic index increased by 4 days after castration and decreased thereafter. ApopTag stain revealed brownish granular pattern in the nucleus of apoptotic cells. DNA fragmentation rate was 0.5% in the control group and began to increase by 1 day after castration and reached to 11.1% by 4 days and decreased thereafter. PCNA stain showed brownish granular pattern in the nucleus of some epithelial cells of the prostatic glands. PCNA labelling index was 2.4% in the control group and reached peak by 3 days after castration and decreased thereafter. Electron microscopically, there was chromatin condensation with margination toward the nuclear membrane by 1 day after castration. Also noted were condensation of cytoplasm, dilatation of RER and nuclear fragmentation.
Apoptotic bodies were formed and phagocytosed by adjacent cells and some apoptotic bodies were found in the lumen of acini. Based on these results, it can be concluded that castration-induced prostatic involution is the result of apoptosis. Detection of DNA fragmentation with ApopTag is a more a accurate method to identify not only apoptotic body formation itself but also the previous step of apoptotic body formation. PCNA labelling index to identify the cellular proliferation seems to play an active role in the early step of apoptosis and be a good tool for investigation of apoptosis.
- Expressions of Vascular Endothelial Growth Factor (VEGF), Phospholipase C-gammal and Ki-67 in Squamous Cell Carcinoma and High Grade Squamous Intraepithelial Lesion of Uterine Cervix.
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Ki Kwon Kim, Jung Ran Kim
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Korean J Pathol. 1998;32(4):290-297.
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- Angiogenesis is an early event in tumorigenesis and facilitates tumor progression and metastasis. This study was performed to evaluate the expression of vascular endothelial growth factor (VEGF), phospholipase C-gamma1 (PLC-gamma1) and Ki-67, and to assess the relationship between them in cervical squamous cell neoplasia. The materials were fifty cervical squamous cell lesions, consisted of thirty HSIL (6 moderate dysplasia, 11 severe dysplasia, 13 carcinoma in situ), and twenty invasive squamous cell carcinoma (ISCC) cases. Immunohistochemical stain for VEGF, PLC-gamma1 and Ki-67 were done. Expression rate of VEGF was significantly higher in ISCC than in HSIL (p=0.012). PLC-gamma1 expression was significantly higher in ISCC than in HSIL (p=0.004).
Ki-67 labelling index was significantly higher in ISCC than in HSIL (p=0.001) and higher in VEGF-positive tumors than in VEGF-negative tumors (p=0.018), but there were no significant differences between PLC-gamma1 expression and Ki-67 labelling index (p>0.05), and between PLC-gamma1 and VEGF (p>0.05). This study suggests that PLC-gamma1 and VEGF may play an important role in tumor cell proliferation and invasion, and these may be a useful marker to predict the possibility of invasion in cervical cancer.
- The Aberrant Expression of p53 Protein in Liver Cell Carcinoma.
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Woo Young Jang, Dong Sug Kim, Ki Kwon Kim, Tae Sook Lee, Chang Yoon Kim, Hong Jin Kim
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Korean J Pathol. 1995;29(5):607-614.
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- This study was carried out to evaluate the aberrant expression of p53 protein using immunobistochemical method in 54 surgically resected liver cell carcinomas and to correlate it with clinical and pathological findings. Twenty five out of 54 cases(46%) showed positive reaction in the nucleus of liver cell carcinoma and negative reaction in associated 30 cases of cirrhosis, one case of adenoma and two cases of adenomatous hyperplasia. The p53 protein expression was associated with alpha-FP level(p<0.05), but not associated with HBsAg positivity. It was significantly associated with WHO classification, Edmondson-Steiner grade and nuclear grade p53(p<0.05), but not associated with tumor size, capsule formation, portal vein invasion, cirrhosis in surrounding tissue, Eggel classification, special cell type and mitosis. In conclusion, our results suggest that the aberrant expression of p53 protein can be an advisory factor, at least, for prognosis evaluation.
- p 53 Protein Expression in Imprint Cytology of Breast Carcinoma.
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Dong Sug Kim, Eun Hi Lee, Ki Kwon Kim, Mi Jin Kim, Soo Jung Lee
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Korean J Cytopathol. 1995;6(1):1-9.
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- This study was carried out to determine the usefulness of imprint cytology for detecting p 53 protein in breast carcinoma. NCL-DO7(Novocastra, U.K.) was used to detect p53 protein immunocytochemically. A total of 33 cases was studied. Immunostaining of imprint cytology with NCL-DO7 was positive in 64%(21\33) and showed relatively high coincident rate (80 %) with immunostaining of formalin-fixed, paraffin - embedded specimen. p 53 protein was related to negative estrogen receptor status, but not to the nuclear grade, lymph node metastasis, or tumor size. The fact that p53 protein expression was not related to nuclear grade might be due to predominance of nuclear grade 3. It was easier to determine the nuclear grade is one of the most important prognostic factors, in imprint cytology than in tissue specimen. p53 protein tended to be stained more strongly in imprint cytology than in tissue.
- Detection of Human Papillomavirus 16/18, 31/33/35 in Verrucous Carcinoma of the Larynx by In Situ Hybridization with Human Papillomavirus DNA Probes.
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Ki Kwon Kim, Sang Sook Lee, June Sik Park, Seung Won Jin, U Ik Sohn
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Korean J Pathol. 1990;24(2):95-102.
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- Verrucous carcinoma of the larynx is a distinct and uncommon variant of well-differentiated squamous cell-carcinoma. The authors hybridized in situ a case of laryngeal verrucous carcinoma with DNA prebes to humman papillomavirus (HPV) 6, 11, 16, 18, 31, 33 and 35. The DNAs from the verrucous carcinoma of larynx hybridized with mixed DNA probes HPV-16/18 and 31/33/35. In addition, there was an evidence of HPV infection based on hybridization with mixed DNA probe HPV-6/11 in the adjacent papilloma tissue. By in situ DNA hybridization techniques, we clearly demonstrated human papillomavirus (HPV-16/18, and 31/33/35) related sequences in this neoplasm. These findings suggest the role of HPV-6/11 in the development of laryngeal papilloma ad HPV-16/18 and 31/33/35 probably on the progression to verrucous carcinoma.
- Detection of Human Papillomavirus DNA by In Situ Hybridization using Biotinylated DNA Probes in Cervical Intraepithelial Neoplasias and Squamous Cell Carcinomas.
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Sang Sook Lee, Ki Kwon Kim, Chai Hong Chung, Seung Won Jin, U Ik Sohn
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Korean J Pathol. 1990;24(1):16-26.
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- The authors examined 9 condylomas, 26 cervical intraepithelial neoplasms(CIN) and 22 invasive squamous cell carcinomas for the presence of human papillomavirus(HPV) DNA sequences by DNA-DNA in situ hybridization. In situ hybridization revealed target HPV DNA sequences mostly in the nuclei of the superficial cells from epithelium which contained either maturation or koilocytotic atypias. With the use of biotinylated HPV DNA probes 6/11, 16/18 and 31/33/35, 42 of the 57(73.7%) were positive with HPV-6/11, 23 with HPV-16/18, 32 with HPV-31/33/35 and 18 with two or more mixed probes. HPV-31/33/35 was wht most prevalent in CIN and invasive squamous cell carcinomas, follwed by HPV-16/18. The incidence of HPV DNA increased from 66.7% to 86.4% with increasing severity of the lesions from condylomas to invasive squamous cell carcinomas. Flat condyloma was most freuently accompanied by CIN.
- Cytologic Diagnosis of hepatocellular Carcinoma by Fine-Needle Aspiration Biopsy.
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Ki Kwon Kim, Eun Sook Chang
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Korean J Cytopathol. 1990;1(1):18-26.
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- CT guided percutaneous fine-needle aspiration(FNA) of the liver for both cytologic and histologic examination has great value in diagnosing liver malignancy. From March, 1986 to April, 1990, 62 patients with the clinical impression of liver malignancy underwent CT guided percutaneous FNA biopsy. Of these, 43 cases were reviewed for this study, 19 were reported to be liver cell carcinoma, 2 were adenocarcinoma, 11 were reported as anaplastic cell present, and the rest (11 cases) were negative (9) or necrotic (2).
Among the 11 cases of the last group, 9 were diagnosed as liver cell carcinoma and 2 were necrotic histologically.
Retrospective review, in order to clarify the casuse of cytologic diagnostic error, of both cytologic and histologic slides of all cases showed discordance of 23% between these diagnoses and sensitivity is 93.9% and specificity is 90.9%.
The reasons were as follows :1) the lack of awareness of tumor cells of well differentiated liver cell carcinoma (4 cases), 2) missed tumor cells due to too scanty cellularity (1 case), 3) improper smear (2 cases) and no tumor cell in the cytologic smears (3 cases). In such cases, at the initiation of FNA, a correct diagnosis of liver malignancy could only be made by a combination of cytologic and histologic examinations. However after three years' experience we can conclude that cytomorphologic features of liver cell carcinoma are sufficiently distinctive from other liver malignancies to be diagnostic
- Adenocarcinoma of Urinary Bladder: 2 cases report.
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Ki Kwon Kim, Eunk Sook Chang, Chai Hong Chung
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Korean J Pathol. 1988;22(4):456-461.
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- Two cases of adenocarcinoma of the urinary bladder with clinical and pathological features, and brief review of the literatureare presented. Case 1: The patient, a 52 year-old man, was admitted to this hospital because of intermittent painless total gross hematuria for 15 years. Cystoscopy was done, and showing a cauliflower mass with broad based diffuse infiltrating lesion at the right anten or portion of bladder. TUR-B was performed. Microscopically, the lesion consisted of colonic metaplastic epithelium with atypical glands and cystic dilatation and adenocarcinoma. Case 2: The patient, a 52-year-old woman, was admitted to this hospital because of total painless gorss hematuria for 1 year.
Cystoscopy was done showing a sessile diffuse mass with ulceration on the dome area. Total cystectomy was performed.
Grossly, the tumor showed an ulcerative tumor mass with elevated nodular margin at the dome of the bladder.
Microscopically, the lesion consisted of anaplastic glands with back to back arrangement and branching glands through the entire thickness of the bladder wall.
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