Journal of Pathology and Translational Medicine

Volume 33(9); September 1999

Original Articles

Histomorphologic Changes of Small Intestinal Mucosa after Irradiation in Rats.: Chan Hwan Kim, Eun Sook Chang, Keon Young Kwon, Kwan Kyu Park, Ok Bae Kim; Korean J Pathol. 1999;33(9):639-651.

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Abstract PDF: Inadvertent application of ionizing radiation, a valuable tool in diagnostic radiology and radiotherapy, results in injury and death of adjacent normal cells, inducing gene mutations or even producing latent cancers. Captopril, an angiotensin I converting enzyme (ACE) inhibitor, has been reported to prevent the structural and functional changes in variable organs, such as lung and kidney, from radiation injury in different experimental animal models. An experiment was carried out to elucidate the radiation-induced histomorphologic changes of small intestine, especially jejunum, and to determine whether captopril can reduce or prevent the radiation-induced injuries in jejunum. Twenty-six healthy Sprague-Dawley rats were used. Experimental group (n=24) was divided into two large groups: the first one (n=16) was treated with two different single dose (9 Gy, 17 Gy) irradiation only and was sacrificed at 12 hours and at 8 weeks following irradiation; the second one (n=8) received captopril 500 mg/l per oral continuously after same doses of irradiation and was sacrificed at 8 weeks. The control group (n=2) was maintained on a stock diet in a same period of experimental group and sacrificed coincidentally. On light and electron microscopy, the 9 Gy and 17 Gy 12 hours groups revealed frequent apoptosis and necrosis but extremely decreased mitotic figures of the crypt cells. However, the 9 Gy and 17 Gy 8 weeks groups and the combined irradiation with captopril groups showed extremely reduced apoptosis and necrosis with increased mitotic figures. There was good correlation between experimental groups in apoptotic count and mitotic count (p<0.05). In the 9 Gy and 17 Gy 12 hours groups, the mucosal surface was focally or diffusely fragmented and the villi were slightly to moderately distorted. Collagen deposition was very mild and confined to the lower portion of the lamina propria. The 9 Gy and 17 Gy 8 weeks groups showed more severe mucosal surface fragmentation even with foci of erosion, short and distorted villi, and more intense collagen deposition. In contrast, the combined irradiation with captopril groups revealed complete regeneration of the mucosal surface epithelium and absent collagen deposition. These findings suggest that the acute radiation injuries to small intestine occur principally in the mucosal crypt cells. Captopril, the ACE inhibitor, might provide a useful intervention in the radiation injuries of intestinal mucosa.

Assay of Proliferative Activity, Clonality and Immortality of.: Hyung Seok Kim, Young Jik Lee, Mee Sook Kim, Hyang Mi Ko, Sang Woo Juhng; Korean J Pathol. 1999;33(9):652-661.

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Abstract PDF: Among the precancerous lesions, dysplasia of the uterine cervix and adenoma of the colon have been widely studied in terms of genetic alterations. However, little has been performed regarding phenotypic alterations of the precancerous lesions. We investigated the relationship among cellular proliferation, clonality, immortality and histopathologic grading of the squamous epithelial lesions of the uterine cervix. Proliferation index (PI) was calculated based on the ratio of the epithelial cells positive for proliferating cell nuclear antigen to the total epithelial cells. Clonality was assayed by X-linked HUMARA polymorphism. For immortality assay, PCR-based TRAP (telomeric repeat amplification protocol) was done and telomerase processivity was calculated by comparison with the positive control. PI increased gradually as the lesions advanced from dysplasia to invasive carcinoma. Among informative case, all of the carcinoma in situ showed monoclonal pattern (7 of 7). Among invasive squamous cell carcinoma, 6 cases showed monoclonal pattern and 2 cases polyclonal pattern. TRAP reaction was positive in 92.6% (25 of 27) of dysplasia (high grade: 14 of 15; low grade: 11 of 12), 95.0% (19 of 20) of carcinoma in situ, 100% (9 of 9) of microinvasive carcinoma, and 92.9% (13 of 14) of invasive carcinoma. It was also positive in 12 of 12 samples of chronic cervicitis or squamous metaplasia near the lesions of dysplasia. There was no difference in TRAP positivity among the dysplasia, carcinoma in situ and invasive carcinoma, whereas telomerase processivity showed significant correlation. These results suggest that proliferative activity and telomerase processivity may be progressive events in oncogenesis, although telomerase activation may be an early event.

Manganese Intoxication in the Rat A neuropathologic study and distribution of manganese in rat brain.: Tae Jung Jang, Jung Ran Kim, Jong Im Lee, Dong Hoon Kim, Ki Kwon Kim, Ji Yong Kim, Hae Kwan Cheong, Hyun Sul Lim; Korean J Pathol. 1999;33(9):662-674.

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Abstract PDF: 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.

Morphometric Study for Muscular and Microvascular Remodeling of Left Ventricular Free Wall and Interventricular Septum in Hypertrophic Cardiomyopathy.: Young Jik Lee, Hyung Suk Kim, Jong Tae Park, Chang Soo Park; Korean J Pathol. 1999;33(9):675-683.

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Abstract PDF: Hypertrophic cardiomyopathy (HCMP) is characterized myofiber hypertrophy and structural remodeling with changes in the proportion of the muscular, vascular, and interstitial compartments. A study was done to determine the structural remodeling patterns and the role of microvasculature of hearts in HCMP. Forty-two postmortem hearts were analyzed including 14 from patients who died of HCMP (group 1), 8 patients with HCMP but who died from extracardiac causes (group 2), 10 patients with ischemic heart disease (group 3), and 10 normal adult hearts (group 4). Macro- and microscopic examination, immunohistochemical study using CD34 antibody, and morphometric studies using image analyzer were performed. Mean cardiac weight and wall thickness were significantly higher in the HCMP group. Myocardial hypertrophy, and a variety of myocardial disarray and fibrosis involved the whole area of the left ventricles with HCMP. The percentage areas of microvessels were 6.40 0.7 in group 1, 5.90 0.6 in group 2, 4.98 0.3 in group 3, 4.85 0.4 in group 4, respectively, and the numbers of microvessels were 198.0 20.7 in group 1, 230.0 22.3 in group 2, 211.7 11.2 in group 3, and 236.4 11.4 in group 4, respectively (mean SE). The percentage area of microvessels was significantly higher in group 1 than in other groups. However, the number of microvessels in that group was lower than in the other groups, although it was statistically insignificant. Since flow-dependent vasodilation is preserved in HCMP, we considered flow-dependent vasodilation the cause of the discrepancy between the area and the number of microvessels. Ischemic changes observed in chronic HCMP and related heart failure were considesed to be due to the relative deficiency of the coronary flow compared to the increasing cardiac mass.

Expression of Surfactant-D Protein and TNF-alpha in the Interaction of Pneumocystis Carinii and Alveolar Macrophages in Pneumocystis Carinii Pneumonia.: Kun Young Kwon, Kwan Kyu Park, Chang Kwon Park, Young June Jeon, Eun Sook Chang; Korean J Pathol. 1999;33(9):684-694.

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Abstract PDF: Alveolar macrophages participate in the host defense against P. carinii, but the mechanisms in degradation and clearance of the organism from lung has not been well established. We observed the transmission and scanning electron microscopic features and evaluated the expression of TNF-alpha and Surfactant-D in the interaction of P. carinii with alveolar macrophages. Expression of TNF-alpha and Surfactant-D in the experimentally induced P. carinii pneumonia in rat was examined by immunohistochemistry and immunoelectron microscopy. Electron microscopically, the alveolar macrophages phagocytized trophozoites and cysts of P. carinii micro-organisms. Immunohistochemically TNF-alpha was strongly expressed in the cytoplasms of alveolar macrophages. Postembedding immunogold labeling for Surfactant-D protein was expressed on the pellicles of trophozoites and cysts, P. carinii micro-organisms in the cytoplasms of macrophages, free floating surfactant materials and multilamellar bodies of type II epithelial cells. We conclude that alveolar macrophages interacted with P. carinii micro-organisms respond with increased expression of TNF-alpha. TNF-alpha may bind to P. carinii and exert a direct toxic effect upon the micro-organisms. Surfactant-D protein may augment binding of P. carinii to the alveolar macrophages and enhance the clearance of the micro-organisms.

Expression of Sialosyl Tn Mucin Antigen in Gastric Adenocarcinoma and Its Relationship with Prognostic Factors.: Sun Hee Chang, Ho Jung Kim, Sun Hee Sung, Hea Soo Koo, Woon Sub Han; Korean J Pathol. 1999;33(9):695-701.

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Abstract: Sialosyl Tn mucin antigen (STn) is a carbohydrate antigen of tumor associated mucin formed by the premature 2~6 sialation of N-acetylgalactosamine. STn has been expressed in several tumor types and showed prognostic significance in colonic carcinoma. The authors evaluated the expression of STn immunohistochemically and correlated its expression with clinicopathologic variables in 100 gastric cancers. In early gastric cancer, STn was expressed in 24 cases out of 50 cases (48%). In advanced gastric cancer, STn was expressed in 48 of 50 (96%). The difference in STn expression between advanced gastric cancer and early gastric cancer was statistically significant. The difference in STn expression between tumors with lymph node metastasis and those without lymph node metastasis, between tubular adenocarcinoma and signet ring cell carcinoma, and between intestinal type and diffuse type adenocarcinoma was statistically insignificant in early or advanced gastric adenocarcinoma. These results suggest that the STn expression plays a role in the tumor progression in both early and advanced gastric adenocarcinomas.

Relationship between HPV Infection and bcl-2 Protein Expression and Apoptosis in Invasive and In Situ Squamous Cell Carcinoma of the Uterine Cervix.: Myoung Ja Chung, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee; Korean J Pathol. 1999;33(9):702-708.

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Abstract PDF: Human papillomavirus (HPV) 16/18 is a causative agent of uterine cervical carcinoma. HPV 16/18 can alter cell cycle regulation through apoptosis. Bcl-2 is an important regulatory gene of apoptosis. A study was done to evaluate the relation between HPV 16/18 and bcl-2 and apoptosis in 21 cases of carcinoma in-situ (CIS), 5 cases of microinvasive carcinoma and 23 cases of invasive squamous cell carcinoma. HPV 16/18 was detected by hybrid capture system (HCS), bcl-2 protein by immunohistochemical method and apoptosis by using the hematoxylin-eosin stained slide. The results were as follows: Expression of the bcl-2 protein was 43% (9/21) in CIS and 26% (6/23) in invasive carcinoma. Expression of the bcl-2 protein was 42% (5/12) in CIS with HPV 16/18 infection, 44% in CIS without HPV 16/18 infection, 20% (2/10) in invasive carcinoma with HPV 16/18 infection and 31% (4/13) in invasive carcinoma without HPV 16/18 infection. Mean apoptotic index (mAI) was 3.36 in CIS, 5.23 in microinvasive and 6.25 in invasive carcinoma. mAI was 3.66 in CIS with HPV 16/18 infection, 2.86 in CIS without HPV 16/18 infection, 6.18 in invasive carcinoma with HPV 16/18 infection and 6.30 in invasive carcinoma without HPV 16/18 infection. Based on these results, we conclude that there are no correlation between HPV infection and bcl-2, and between HPV infection and apoptosis in invasive and in situ carcinoma of the uterine cervix, and apoptosis is increased according to tumor progression.

Expression of p27kip1, Cyclin D1 and p53 Protein in Ductal Carcinoma In Situ of the Breast.: Young Lyun Oh, Sang Yong Song, Jong Sun Choi, Young Hyeh Ko, Hwoe J Ree, Geung Hwan Ahn; Korean J Pathol. 1999;33(9):709-716.

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Abstract PDF: p27(kip1) protein, a cyclin-dependent kinase inhibitor, has been reported to be a powerful negative prognostic marker in patients with breast carcinoma. However, to this day, studies on p27(kip1) protein expression in ductal carcinoma in situ (DCIS) have been extremely limited. We studied the immunohistochemical expression of p27(kip1) protein in 49 cases of the DCIS and compared the findings to the clinicopathologic parameters, cyclin D1, p53 and estrogen receptor (ER). Positive nuclear staining of p27(kip1) protein was identified in 23 (46.9%) cases. The p27(kip1) protein expression correlated positively with the cyclin D1 immunopositivity (p<0.005) and ER expression (p<0.005). No significant associations were seen in the p27(kip1) protein expression and clinicopathologic parameters. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with ER expression (p<0.001). The p53 protein expression was identified in 30.6% and seemed to be correlated inversely with ER expression (p=0.06). The DCISs with high grade nuclei were more likely to be p53-positive (p<0.05). Our data suggest that the expression of p27(kip1) protein as well as cyclin D1 and p53 protein may be influenced by the ER status in DCIS. The significantly positive correlation of p27(kip1) protein and cyclin D1 expression (p<0.005) supports the theory that the balance of the two opposing signals is important in determining the cell proliferation in breast cancers. Therefore, a comprehensive understanding of loop reaction of p27(kip1)-cyclin D1-ER may be necessary for the treatment of DCIS.

Immunohistochemical Findings in 10 Cases of Inflammatory Myofibroblastic Tumor.: Soo Jin Jung, Mi Seon Kang, Chang Hoon Lee, Sook Hee Hong, Hye Kyoung Yoon; Korean J Pathol. 1999;33(9):717-722.

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Abstract PDF: A wide range of denomination has been used for inflammatory myofibroblastic tumor (IMT). IMT is not entirely homogeneous, even though it shows some overlapping histologic features such as haphazard proliferation of spindle cell and polymorphic chronic inflammatory cell infiltraion. The spindle cell is considered to be of myofibroblastic origin but follicular dendritic cell origin was reported recently. IMT is known as nonneoplastic, aberrant inflammatory response. However, IMT could show local invasion, recurrence, vascular invasion, and malignant transformation, and clonal characteristics and aneuploidy of IMT support the hypothesis that IMT may be a neoplastic process. In order to define the nature of spindle cell of IMT, immunohistochemical stains for smooth muscle actin (SMA), vimentin (VMT), lysozyme, S-100 protein, cytokeratin, CD21 were done. Additional immunohistochemical stains for MIB-1 for proliferating activity and LMP (latent membrane protein) for Epstein-Barr virus (EBV) were done. IMTs were composed of each 2 cases from lung, liver and lymph node and one case from common bile duct, maxillary sinus, bladder and thigh, and were histologically subclassified according to Coffin et al. Nine cases (90%) were positive for SMA and VMT, but no correlation between SMA and VMT immunoreactivity and histologic types was identified. Five cases (50%) were positive for lysozyme and S-100 protein, and histologic type III was negative for lysozyme and S-100 protein, and immunoreactivity for S-100 protein was different according to the histologic subtypes. All 11 cases were negative for CD21 and EBV LMP. MIB-1 labelling index was less than 1% in all cases. In summary, the spindle cell is regarded as myofibroblastic origin rather than follicular dendritic cell origin. Relationship with EBV is not clear, and negligible MIB-1 reaction suggests that IMT might have a good prognosis.

Correlation of Ki-67, p53 and bcl-2 Expression with Grade and Behavior of Ependymoma.: Jae Ho Han, Tai Seung Kim; Korean J Pathol. 1999;33(9):723-728.

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Abstract PDF: Ependymomas constitute no more than 5 to 7% of all primary CNS neoplasm and their biologic behavior is difficult to predict by microscopic appearances. Recently, many studies have attempted to correlate biologic behavior with tumor proliferation index, tumor suppressor gene and oncogene using immunohistochemical stains. We evaluated 25 cases of surgically resected intracranial ependymomas for the proliferation activity using Ki-67, and expression of p53 and bcl-2 protein with regard to the prognosis. The cases were divided into 17 ependymomas (WHO Grade II), 3 papillary ependymomas (WHO Grade II), and 5 anaplastic ependymomas. Clinically, the patients were divided into two groups, recurrent (18 cases) or non-recurrent (7 cases). The Ki-67 proliferation index was significantly higher in the recurrent group (p<0.05) and in the younger ages (correlation index=0.534). Although Ki-67 proliferation index was higher in anaplastic ependymoma, it was not significant statistically (p>0.05). p53 protein expression tended to increase in the patients who had anaplastic ependymoma and in the recurrent group. bcl-2 expression was not correlated with histologic grade or recurrence of the tumor. We conclude that Ki-67 proliferation index and p53 expression are important markers for predicting biologic behavior of ependymoma.

Case Reports

Inflammatory Myofibroblastic Tumor of the Mesentery: A case report.: Sung Jig Lim, Gou Young Kim, Jae Hoon Park, Youn Wha Kim, Yong Koo Park, Ju Hie Lee, Moon Ho Yang; Korean J Pathol. 1999;33(9):729-732.

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Abstract PDF: Inflammatory myofibroblastic tumor or inflammatory pseudotumor is characterized by spindle cell proliferation with inflammatory cell infiltration, predominantly plasma cells and lymphocytes. We have experienced a case of inflammatory myofibroblastic tumor of the mesentery in a 57-year-old male patient with intermittent abdominal pain. On computer tomography, a well demarcated mass was seen in the mesenteric side of the ascending colon. Right hemicolectomy was performed under the impression of the metastatic tumor of lymph nodes. Grossly, a rather well-circumscribed gray white mass was noted in the mesentery of the ascending colon. Microscopically, the lesion consisted of plump spindle cells and accompanying inflammatory cellular infiltrates. The spindle cells were positive for vimentin.

Leiomyosarcoma of the Pancreas: A case report.: Bong Kyung Shin, Jung Suk Moon, Hwa Eun Oh, Nam Hee Won, Jong Sang Choi; Korean J Pathol. 1999;33(9):733-736.

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Abstract PDF: Most of the malignant tumors of the pancreas are adenocarcinomas arising from the ductal epithelium. Primary leiomyosarcoma of the pancreas, even though it is the most common sarcoma of the pancreas, is very rare. We present a case of leiomyosarcoma of the pancreas, probably primary, with metastases to the stomach, lymph nodes, and abdominal wall. A 52-year-old woman visited the hospital with vague right upper abdominal pain and weigh loss of 6 kg for 2 months. The radiological and endoscopic examination revealed that she had a large heterogeneous mass, 11 cm in size, in the pancreatic body and tail, a 4 cm-sized mass in the paraaortic area, and a 3 cm-sized polypoid mass in the stomach. Histologically, they were all similar to one another and composed of markedly pleomorphic cells. Immunohistochemical and electron microscopic studies showed definite smooth muscle differentiation of the tumor cells. Two months later, the patient underwent an excision of a new 3 cm mass in the right lower abdominal wall, showing features of well differentiated leiomyosarcoma.

Verumontanum Mucosal Gland Hyperplasia: A case report.: Mi Sun Choe, Tae Jin Lee, Eun Sil Yu, Jae Y Ro; Korean J Pathol. 1999;33(9):737-740.

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Abstract PDF: Verumontanum mucosal gland hyperplasia (VMGH) is a relatively common benign proliferative lesion which was first described by Gagucas et al in 1995. VMGH is usually found in radical prostatectomy or transurethral resection specimens and rarely in needle biopsy specimens. The histologic feature of VMGH is characterized by well-circumscribed proliferation of small glands and thus VMGH may mimic low grade adenocarcinoma. We report a case of VMGH from a 61-year-old man. The lesion coexisted with prostatic adenocarcinoma on radical prostatectomy specimen. The lesion was a well circumscribed microacinar proliferation which was present between the openings of ejaculatory ducts. The acini consisted of two cell layers with inner secretory cuboidal epithelium and outer basal cell. Typically, the lumen contained many corpora amylacea. Nuclear pleomorphism, prominent nucleolus, or mitotic figure was not identified. Because of small gland proliferation of VMGH, this lesion can be confused with other small gland proliferative lesions, such as low grade adenocarcinoma, atypical adenomatous hyperplasia, basal cell hyperplasia, mesonephric hyperplasia, and nephrogenic adenoma. To avoid misdiagnosis of VMGH as carcinoma, one should be familiar with this lesion.

Cerebral Amyloid Angiopathy: A report of two cases.: Kee Taek Jang, Ghee Young Choe, Yeon Lim Suh, Je Geun Chi; Korean J Pathol. 1999;33(9):741-744.

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Abstract PDF: Cerebral amyloid angiopathy (C.A.A) is characterized by the extracellular amyloid protein deposition in the vessel walls of the brain and meninges. It has been estimated to account for 5 to 10% of all primary, nontraumatic brain hemorrhage. We report two cases of C.A.A causing nontraumatic intracerebral hemorrhage in the frontal lobe. The first case was a 60-year-old female who was admitted for the left hemiplegia and dysarthralgia. Brain CT revealed right frontal lobe hemorrhage. The second case was a 72-year-old male who was admitted for amnesia and gait disturbance. Clinical impression was Alzheimer's disease. Brain MRI revealed multifocal small hemorrhage in the right frontal lobe. Microscopically, both cases showed dilated small arteries of superficial cortex and meninges with hyalinization. Some vessels showed microaneurysm and fibriniod necrosis. Congo-red stain also exhibited birefringence under polarized light. There was no evidence of Alzheimer's disease.

Symptomatic Graular Cell Tumor Involving Intra- and Suprasellar Area: A case report.: Se Hoon Kim, Sun Ho Kim, Tai Seung Kim; Korean J Pathol. 1999;33(9):745-750.

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Abstract PDF: Symptomatic parasellar granular cell tumor is a very rare tumor. To the best of our knowledge, 43 cases was be found in the English literatures. We recently experienced a case of a parasellar granular cell tumor in a 61-year-old female who had bilateral temporal hemianopsia and severe panhypopituitarism. The tumor was composed of diffuse sheets of polygonal cells with abundant eosinophilic PAS positive granular cytoplasm. In the immunohistochemical and ultrastructural examinations, the tumor failed to show any evidence of Schwann cell or glial differentiation. These findings suggest that granular cell tumor has heterogenous cell types of origin.

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