Anti-NSP4 antibody can block rotavirus-induced diarrhea in mice.

BACKGROUND: Rotavirus infection is the most common cause of infectious diarrhea and gastroenteritis among children worldwide. The viral proteins (VP), especially VP4- and VP7-induced neutralizing antibodies, were considered to be critical in protective immunity to rotavirus disease. However, whether the antibody to rotavirus nonstructural protein 4 (NSP4) protects against rotavirus-induced diarrhea directly is not completely clear, especially for the protective time course. MATERIALS AND METHODS: To obtain direct evidence, 12-day-old ICR mice were treated with NSP4 and entire rotavirus to induce diarrhea. RESULTS: Both NSP4 and rotavirus-treated mice developed diarrhea, which was accompanied by histological changes in the small intestine compared to age-matched control mice. Anti-NSP4 antibody demonstrated protection against both entire rotavirus-induced diarrhea and NSP4-induced diarrhea. The histological changes in the small intestinal were reversible. These data show that early intervention with anti-NSP4 antibody can prevent rotavirus-induced diarrhea in mice; late intervention with anti-NSP4 antibody could halt diarrhea progression in mice. CONCLUSIONS: Our findings demonstrate for the first time that administration of anti-NSP4 antibody is effective both prior to and during the time course of rotavirus infection. These observations extend our knowledge of rotavirus infection and its therapeutic options.

Diabetic atherosclerosis mouse models.

Coronary heart disease (CHD) due to atherosclerosis is the leading cause of death in the USA, and accelerated CHD has emerged as a leading cause of morbidity and mortality in diabetic patients in the USA and worldwide. This has highlighted the importance and urgency of studying the mechanism of diabetic atherosclerosis and exploring therapeutic options. Due to its unique advantages over other animal models, the mouse is the most used model for studying the mechanism of diabetes-accelerated atherosclerosis and exploring effective therapeutic approaches. In the past decade, several diabetic atherosclerosis mouse models have been established. Currently, however, there is no ideal animal model for diabetic atherosclerosis. To determine the characteristics of the models that more closely resemble human diabetic atherosclerosis disease, this review focuses on the common diabetic atherosclerosis mouse models with respect to the following issues: (1) whether the mice retain diabetic condition; (2) whether the diabetes accelerates atherosclerosis or increases atherogenic inflammation; (3) whether these factors respond to medical interventions. The discussion is aimed at identifying different diabetic mouse models and their features, in order to heighten awareness of the appropriate models that may provide useful tools for studying the mechanism of diabetes-accelerated atherosclerosis and evaluating therapeutic options.

Association of 22q11 deletion with isolated congenital heart disease in three Chinese ethnic groups.

BACKGROUND: Congenital heart disease (CHD) is the most common type of heart disease among children. About 75% of DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS) includes CHD. A deletion within chromosome 22q11.2 has been identified in the majority of patients with DGS and VCFS. And 22q11.2 deletion has become one of the markers used to study CHD in these syndromes. Whether 22q11.2 deletion is associated with isolated CHD is not known and was the topic of this study. METHODS AND RESULTS: We studied the 22q11.2 deletion in three Chinese ethnic groups (Tai, Bai and Han people) with 19 sporadic, isolated CHD by genotype and haplotype analysis with D22S420 etc. 11 consecutive polymorphic microsatellite markers. Among 19 isolated CHD patients, four had Tetralogy of Fallot (TOF), five exhibited Ventricular Septal Defect (VSD), five showed Atrial Septal Defect (ASD) and 5 had Patent Ductus Arteriosus (PDA). In some isolated CHD patients, 3 Mb and 1.5 Mb deletion to chromosome 22q11.2 was found. 2 of 4 TOF (50%) and 1 of 5 VSD (20%) and 1 of 5 PDA (20%) respectively were found to have deletions at D22S944. CONCLUSIONS: 22q11.2 deletion can be detected in isolated TOF, VSD and PDA of three Chinese ethnic groups, without detectable 22q11.2 deletion in those isolated ASD patients examined thus far. Our finding may be the first to show the 22q11.2 deletion in sporadic, isolated PDA/VSD patients whose family members are without CHD. In addition, D22S420 etc. 11 consecutive polymorphic microsatellite markers are very useful for the determination of 22q11.2 deletion in isolated CHD in China.

Isolated congenital heart disease is associated with the 22q11 deletion even though it is rare.

It is well known that a deletion within chromosome 22q11.2 has been identified in most cases of congenital heart disease (CHD) with DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS). Whether the 22q11.2 deletion is associated with isolated CHD is controversial. Our data is consistent with previous publications which show that the 22q11.2 deletion is associated with isolated CHD even though it is rare.

Histological patterns and associated PSA levels for prostatic adenocarcinoma following brachytherapy.

Changes in morphologic patterns over a time course following radiation and their corresponding PSA levels were investigated. A total of 60 patients with prostatic adenocarcinoma treated with brachytherapy between 1993 and 2003, who had at least one positive post-radiation biopsy, were evaluated for their morphologic patterns as well as the associated PSA levels. A total of 86 positive post-radiation biopsies were performed. There were 17 patients with more than 1 positive post-radiation biopsy and 43 patients with single positive biopsy. Among the 17 with more than 1 positive biopsy, the morphologic patterns of treatment effect were commonly followed by patterns without treatment effect on subsequent biopsies. The morphology without treatment effect followed by treatment effect was infrequent. Furthermore, over a time course, the later the positive post-radiation biopsy, the much more common the morphologic pattern without treatment effect was observed. Compared to the morphologic pattern with treatment effect, the morphology without treatment effect was associated with a significantly higher PSA level (mean 0.69 versus 2.78 ng/ml, p<0.05). An increase in the Gleason's score in recurrent carcinoma was also noted in 14% of the cases. Multiple factors were likely involved in the variability of the changes in post-radiation morphologic patterns. A new neoplastic process was particularly considered in some of our cases, which may merit clinical attention. The significant difference in PSA levels between carcinomas without treatment effect and those with treatment effect also suggested a post-radiation variation of tumor biology and a potential role of these patterns in monitoring and managing the patients treated with brachytherapy.

Fascin over expression is associated with dysplastic changes in sinonasal inverted papillomas: a study of 47 cases.

Sinonasal inverted papilloma (IP) is a primary benign lesion with a tendency for local recurrence. Malignant transformation may develop in up to 15% of cases. Fascin (Fascin 1) is an actin cross-link binding protein required for the formation of actin-based cell-surface protrusions and cell motility. Fascin up-regulation in lung, gastric, breast and hepatobiliary carcinomas correlates with aggressiveness and decreased survival. Here we evaluate immunohistochemical expression of fascin in 47 sinonasal IPs from 34 patients. Fascin over-expression is significantly more common in sinonasal IP with high-grade dysplasia than in those with no dysplastic or low-grade dysplastic epithelium (P = 0.0001). No significant change in fascin expression is seen with recurrence. Over expression of fascin in high-grade dysplastic epithelium in IP may be associated with tumor progression and malignant transformation.

Streptozotocin-induced diabetic models in mice and rats.

Streptozotocin (STZ) is an antibiotic that can cause pancreatic ß-cell destruction, so it is widely used experimentally as an agent capable of inducing insulin-dependent diabetes mellitus (IDDM), also known as type 1 diabetes mellitus (T1DM). This unit describes protocols for the production of insulin deficiency and hyperglycemia in mice and rats, using STZ. These models for diabetes can be employed for assessing the mechanisms of T1DM, screening potential therapies for the treatment of this condition, and evaluation of therapeutic options.

Clear cell adenocarcinoma of urinary bladder and urethra: another urinary tract lesion immunoreactive for P504S.

CONTEXT: Clear cell carcinoma of the urinary bladder/ urethra is a rare tumor histologically resembling the neoplasms in the female genital tract. Adequate characterization of this tumor has been hampered by its rarity. alpha-Methylacyl-CoA racemase (AMACR)/P504S has been reported to be positive in prostatic adenocarcinoma, papillary renal cell carcinoma, and gastrointestinal neoplasmas; however, it has never been studied in clear cell carcinoma of the lower urinary tract. OBJECTIVE: To investigate the immunohistochemical staining profile in 4 primary clear cell carcinomas of the urinary tract, including P504S, which has not been previously evaluated in these tumors. DESIGN: Four cases of clear cell adenocarcinoma were retrieved from our archives: 2 cases from the urinary bladder (one each from a man and a woman) and 2 cases from the urethra (both from women, 1 in a diverticulum). Immunohistochemistry performed on the cases were P504S, K903, cytokeratin (CK) 7, CK20, CA 125, and p63. RESULTS: We found that clear cell carcinomas had a distinct immunoreactive profile: strongly positive for P504S, K903, and CK7, and negative for p63. Two cases were also positive for CA 125 and CK20. CONCLUSION: The immunohistochemical profile of clear cell carcinomas shares some similarity to conventional urothelial carcinoma; however, it deviates from those tumors in being positive for P504S and negative for p63. This staining profile may suggest a nonurothelial origin for these tumors, may serve as a useful tool in the differential diagnosis of this tumor, and may reflect its etiology. Because similar expression of P504S is also seen in nephrogenic adenomas, this marker should not be used to differentiate nephrogenic adenomas from clear cell adenocarcinomas.

Sarcomatoid carcinoma after radiation treatment of prostatic adenocarcinoma.

We report 2 patients with conventional prostatic adenocarcinoma who developed sarcomatoid carcinoma of probable prostatic origin 6 and 2.5 years after radiation treatment (seed implantation and external beam). Our cases had histologic features consistent with those cases previously reported in the literature. The tumors consisted of spindle cells with large hyperchromatic nuclei and a pattern mimicking a sarcoma. Immunohistochemical studies showed the tumors to be weakly positive for EMA, CK7, and vimentin. Ki67 staining showed positivity in more than 50% of tumor cells. The tumors also stained diffusely positive for p53 and p63. PSA and PAP were negative. Clinically, the sarcomatoid carcinomas appeared to be of prostatic origin. The pathogenesis of the tumors is still uncertain but most likely represent a radiation-induced dedifferentiation of prostatic adenocarcinoma.

Expression of PAX8 in nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract: evidence of related histogenesis?

Recent evidence has showed that nephrogenic adenoma is a true "nephrogenic" lesion derived from the proliferation of exfoliated and implanted renal tubular cells in the urinary tract, a process that closely resembles the formation of endometriosis. This new concept has led to the identification of renal transcription factor PAX2 as a diagnostic marker for nephrogenic adenoma. PAX8 is another transcription factor structurally and functionally related to PAX2. Both are cell lineage restricted transcription factors expressed in normal and neoplastic tissues of related origin, including renal tubular cells in both fetal and adult kidneys. In this study, we investigated the expression of PAX8 in nephrogenic adenoma and its mimics. We report here that PAX8 was detected in all nephrogenic adenomas (N=35) and clear cell adenocarcinoma of the lower urinary tract (N=7), but not in prostate adenocarcinoma (N=100), adenocarcinoma (N=9), squamous cell carcinoma (N=5), or urothelial carcinoma (N=48) of the urinary bladder and its variants. PAX8 was neither detected in normal urothelium of the urinary bladder nor in prostate glands and stroma. PAX2 was also detected in 2 of the 7 clear cell adenocarcinomas of the lower urinary tract. We suggest that PAX8 is an additional marker for identifying nephrogenic adenoma. Expression of PAX8 or PAX2 in both nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract may indicate a possible related tissue origin for these 2 lesions; both may be derived from proliferating renal tubular cells in the urinary tract. In addition, detection of PAX8 or PAX2 in clear cell adenocarcinoma of the lower urinary tract is helpful in differentiating it from urothelial carcinoma and its variants and adenocarcinomas of the urinary bladder or of the prostate.

PNL2 melanocytic marker in immunohistochemical evaluation of primary mucosal melanoma of the head and neck.

BACKGROUND: Histologic diagnosis of mucosal melanoma of the head and neck is difficult, requiring immunohistochemical stains which are less reliable than in cutaneous lesions. PNL-2 is a novel marker that has not been examined in mucosal melanoma. METHODS: Nine formalin-fixed tissue sections of mucosal melanoma were stained with PNL-2, human melanoma black (HMB)-45, Melan-A, S-100, and microphthalmia transcription factor (MITF). RESULTS: Disease in all 9 patients arose from the sinonasal mucosa. Rates of diffuse positive staining with the 4 stains were PNL-2 (77.8%), HMB-45 (77.8%), Melan-A (50%), S-100 (87.5%), and MITF (40%). In 3 patients, PNL2 staining was superior to Melan-A or MITF. CONCLUSION: We report the first characterization of PNL-2 staining in head and neck mucosal melanoma. PNL-2 demonstrates high sensitivity for mucosal melanoma, likely superior to Melan-A and MITF, and comparable to HMB-45, with specificity superior to S-100. We advocate inclusion of PNL2 as an important adjunctive marker in the evaluation of these lesions.

Inflammatory myofibroblastic tumor of larynx: a benign lesion with variable morphological spectrum.

Inflammatory myofibroblastic tumor is a recently characterized lesion, composed of exuberant myofibroblastic proliferation and an inflammatory component. Its etiology remains controversial, as to whether this represents a benign tumor with limited potential to recur or progress. Exaggerated response to trauma or infection has also been implicated. Only a few cases of laryngeal inflammatory myofibroblastic tumor have been described in English after it has been assigned the new name. The prototype lesion, inflammatory pseudotumor, has been best described in association with the lung but has also been reported involving various organs. We report 2 additional cases with a considerable variation in the presentation and histology of the lesion, thus expanding the morphological spectrum of the entity. Both lesions appeared aggressive in clinical presentation. One case had relatively more pleomorphic appearance and increased mitotic rate. Both lesions were surgically resected, and complete voice preservation was achieved. No postoperative complications or recurrence were noticed. This uncommon neoplasm may appear clinically as a large infiltrating mass and may be mistaken as a malignant growth. Conservative resection of the tumor may provide a cure with adequate voice preservation.

Atypical fibrous histiocytoma of the scrotum.

Atypical fibrous histiocytoma is a rare neoplasm. A scrotal location for this tumor is even more unusual. We report a case of a 90-year-old man with scrotal atypical fibrous histiocytoma. Our case had histologic features consistent with those cases previously reported in the literature. The tumor consists of cells with large hyperchromatic irregular nuclei, bizarre multinucleated cells (monster cells), and xanthomatous cells with large prominent nuclei set in a background of classic fibrous histiocytoma. Rare mitotic figures are identified. Immunohistochemical studies showed the tumor cells to be positive for vimentin, smooth muscle actin, desmin, KP-1, factor XIIIa, and MIB-1 (less than 10%). In addition to the expected immunohistochemical studies, the tumor stained diffusely positive for CD117. To our knowledge, this is the first report of atypical fibrous histiocytoma of the scrotum.

Angiomyolipoma of the bladder.

Angiomyolipoma of the bladder is an extremely rare neoplasm. We report a case of a 55-year-old woman with an angiomyolipoma of the bladder visualized on pelvic sonogram as a 5 mm polyp in the floor of the bladder. The lesional tissue consisted of spindle cells, epithelioid cells, and adipocytes, with occasional thick-walled blood vessels. Immunohistochemical studies showed the spindle and epithelioid cells to be focally positive for HMB-45 and diffusely positive for actin and muscle cell antigen (HHF-35), which confirmed the diagnosis of angiomyolipoma. A review of the recent literature on the pathogenesis of angiomyolipoma follows.