Neuronal apoptosis and inflammatory responses in the central nervous system of a rabbit treated with Shiga toxin-2

<p>Abstract</p> <p>Background</p> <p>Shiga toxins (Stxs) are the major agents responsible for hemorrhagic colitis and hemolytic-uremic syndrome (HUS) during infections caused by Stx-producing <it>Escherichia coli </it>(STEC) such as serotype O157:H7. Central nervous system (CNS) involvement is an important determinant of mortality in diarrhea associated-HUS. It has been suggested that vascular endothelial injuries caused by Stxs play a crucial role in the development of the disease. The current study investigates the relationship between the cytotoxic effects of Stxs and inflammatory responses in a rabbit brain treated with Stx2.</p> <p>Methods</p> <p>In a rabbit model treated with purified Stx2 or PBS(-), we examined the expression of the Stx receptor globotriaosylceramide (Gb3)/CD77 in the CNS and microglial activation using immunohistochemistry. The relationship between inflammatory responses and neuronal cell death was analyzed by the following methods: real time quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) to determine the expression levels of pro-inflammatory cytokines, and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method to detect apoptotic changes.</p> <p>Results</p> <p>Gb3/CD77 expression was detected in endothelial cells but not in neurons or glial cells. In the spinal cord gray matter, significant levels of Gb3/CD77 expression were observed. Severe endothelial injury and microvascular thrombosis resulted in extensive necrotic infarction, which led to acute neuronal damage. Conversely, in the brain, Stx receptor expression was much lower. The observed neuropathology was less severe. However, neuronal apoptosis was observed at the onset of neurological symptoms, and the number of apoptotic cells significantly increased in the brain at a later stage, several days after onset. Microglial activation was observed, and tumor necrosis factor (TNF)-α and interleukin (IL)-1β mRNA in the CNS parenchyma was significantly up-regulated. There was significant overexpression of TNF-α transcripts in the brain.</p> <p>Conclusion</p> <p>This study indicates that Stx2 may not directly damage neural cells, but rather inflammatory responses occur in the brain parenchyma in response to primary injury by Stx2 in vascular endothelial cells expressing Gb3/CD77. These findings suggest that neuroinflammation may play a critical role in neurodegenerative processes during STEC infection and that anti-inflammatory intervention may have therapeutic potential.</p

Successful treatment of desmoid tumor of the chest wall with tranilast: a case report

<p>Abstract</p> <p>Introduction</p> <p>Desmoid tumor is characterized by infiltrative growth and local recurrence often occurs after surgery. To reduce the local recurrence rate, adjuvant therapy, such as radiotherapy and pharmacotherapy with cytotoxic agents, anti-estrogen agents and non-steroidal anti-inflammatory drugs, is often applied. In addition, these non-surgical treatments are also performed in patients with unresectable desmoid tumors. We successfully treated a patient with a desmoid tumor with tranilast; an anti-allergic agent.</p> <p>Case presentation</p> <p>A 48-year-old Japanese man with a slow-growing desmoid tumor on his chest wall was treated with an oral administration of tranilast (300 mg per day, three times a day). Two years and two months after the commencement of his therapy, the tumor became impalpable. At this time, the oral administration of tranilast was discontinued. Two years after discontinuation of the treatment, a physical examination showed no recurrence of the tumor and he continued in a state of remission. We were successfully able to reduce the size of the tumor and thereafter maintain the reduced size.</p> <p>Conclusion</p> <p>Tranilast was clinically effective in our case, and is probably comparable to cytotoxic agents or anti-estrogen agents. Because tranilast has substantially fewer adverse effects than cytotoxic agents, it could be a very useful therapeutic agent for desmoid tumor.</p

CEREBRAL VASCULAR CHANGES IN SYSTEMIC LUPUS ERYTHEMATOSUS

Cerebral vascular lesions of 26 cases in systemic lupus erythematosus during a period from 1963 to 1978 were examined histologically and the following conclusions were made: 1.The prominent vascular changes of the brain were thrombosis, fibrinoid degeneration, endothelial swelling and proliferation, arteriolosclerosis, and perivascular infiltration of inflammatory cells. 2.From clinic-pathological viewpoints, thrombosis seemed to play an important role in the development of neurological signs. In five cases, characteristic granular or homogeneous thrombi were observed in the small blood vessels including venule. Infarct without proved vascular obstruction but probably due to thrombosis was seen in four cases. The true character of the granular thrombi was not determined, either electronmicroscopically or immunohistochemically. These suggested the presence of a tendency for in situ formation of thrombus. 3.Fibrinoid degeneration seen in four cases mainly affected arterile of less than 50 µm in diameter in the cerebral cortex, basal ganglia, and brain stem. This change of arteriole did not play a significant role in neurological signs. 4.Endothelial swelling and proliferation of the small blood vessels were prominent in the cases with thrombosis and fibrinoid degeneration. 5.Perivascular infiltration of the inflammatory cells was observed in about one-half of the cases but its significance was not clear

GLIAL FIBRILLARY ACIDIC PROTEIN-POSITIVE CELLS IN HUMAN ANTERIOR PITUITARY-IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL STUDY

The GFAP-positive cells in the five human anterior pituitaries obtained at autopsy were investigated immunohistochemically and ultramicroscopically. The GFAP-positive cells varied in number from case to case and were identical with the so-called stellate cell. The stellate cells were also involved in the follicular formation. The electron microscopic study showed the various features of these cells. Some had a narrow rim of perikaryon and slender cytoplasmic processes with a moderate number of mitochondria and endoplasmic reticula and others formed an intercellular lumen and follicles with well developed Golgi apparatus, vesicular body and lysozome. The intermediate filaments were rather abundant and the anit-GFAP-positive products were thought to be related with these filaments. The stellate cells were non-granulated so far as examined. The variability of their ultrastructural features were thought to reflect the different physiological state of the pituitary. The present findings suggested the important role of the stellate cells in the function of the endocrine secretary cells. Their origin was also discussed

A STUDY OF LEUKEMIC CELL INFILTRATION IN THE TESTIS AND OVARY

The behavior of leukemic cell infiltration in the testis or ovary was examined on 99 autopsy cases of various leukemia, which were performed in the Department of Pathology, Tokyo Medical and Dental University, from 1964 to 1975. The incidence of leukemic cell infiltration was 48.5% in the testis and 58.1% in the ovary. The frequency of leukemic cell infiltration in the testis or ovary itself showed no significant increase in recent years, although median survival time became longer by a more aggressive combination chemotherapy. These findings show that the testis and ovary are essentially a preferred site of leukemic cell infiltration. Especially in acute monocytic leukemia, leukemic cell infiltration was revealed in all cases. In addition, short discussions were made on the role of sex hormones in the infiltration, proliferation, and persistence of leukemic cells of each type of leukemia in the testis or ovary

A cotyledonoid dissecting leiomyoma with an intravascular component and adenomyosis accompanied with possible multiple lung metastases: A case report

A cotyledonoid dissecting leiomyoma (CDL) is a rare variant of a uterine smooth muscle cell tumor and is characterized by intramural and extrauterine growth patterns with dissection of the uterine myometrium.We encountered a case of a CDL with multiple lung nodules. Computed tomographic and magnetic resonance imaging results revealed the presence of a multilobulated abdominal mass with cystic components contiguous to the uterine corpus and well-demarcated nodules measuring ≤2 cm in diameter in the bilateral lungs. Simple hysterectomy and bilateral salpingo-oophorectomy were performed.Macroscopically, a placenta-like tumor protruded from the medial fundus of the uterine corpus toward the intraluminal and peritoneal cavities. Histologically, the tumor was composed of neoplastic spindle cells with hyalinized degeneration and vascular proliferation. Endometrial glands with stroma and vascular invasion were also noted.This is the first report of a CDL with possible metastasis. Histological features, including intravascular growth, may predict the aggressive behavior of this tumor. Keywords: Adenomyosis, Leiomyoma, Smooth muscle tumo

Leptomeningeal dissemination of cerebellar pilocytic astrocytoma

✓ A case of surgically treated pilocytic astrocytoma in the cerebellar vermis is reported in a patient who subsequently demonstrated multiple subarachnoid nodular masses in the cerebrum and spinal cord 6 years after the initial surgery. The nodular tumors did not indicate a growth tendency on computerized tomography or magnetic resonance imaging over a 2-year observation period. The histology of the nodular masses in the cerebrum and spinal cord was similar to that of the original tumor. The bromodeoxyuridine labeling index indicated low proliferative activity (0.5%). The peculiar pattern of dissemination of the pilocytic astrocytoma is described.</jats:p