Epidermoid Cyst Derived from an Accessory Spleen in the Pancreas

A rare case of splenic epidermoid cyst (SEC) of the pancreas discovered in a 32-year-old Japanese female is reported. The lesion, 5x6cm in size including caseous material and serous fluid in the lumen, was discovered by ultrasonography and computed tomography at the tail of the pancreas and was easily removed. Histopathologically, the cystic wall consisted of three components: the inside was lined by mature squamous epithelium with keratinization, the middle layer consisted of splenic pulp with a sinus structure, and the peripheral layer was dense fibrous connective tissue in which some involutional pancreatic ducts and islets were recognized. The literature about SEC of the pancreas is discussed in comparison with other types of epidermoid cyst including lymphoepithelial cyst and dermoid cyst in the pancreas. Acta Pathol Jpn 41: 916 921, 1991.     

Atypical Glomus Tumor in the Mediastinum: A Case Report with Immunohistochemical and Ultrastructural Studies

A case is reported of atypical glomus tumor occurring in the posterior inferior mediastinum of a 26-year-old woman complaining of severe back pain. The tumor was composed of atypical small, round tumor cells with scattered mitotic figures. In addition to sheet-like, diffuse proliferation of the tumor cells, some areas of the tumor contained small “glo-moid” cells arranged in organoid and hemangiopericytoma-like patterns. Immunohistochemically, many tumor cells were positive for muscle-type actins and a few cells were focally positive for desmin. Ultrastructural studies revealed smooth muscle features of tumor cells, that is, pinocytotic vesicles, external laminas, dense plaques, and occasional thin filaments with dense bodies. The patient remained well for 5 years and 4 months after the operation without additional radiation and chemotherapy. The tumor was diagnosed as an atypical, or low-grade malignant, glomus tumor morphologically. It seems important to recognize the presence of this type of tumor in sites other than extremities and to differentiate it from other malignant small, round cell tumors.     

Small vessel vasculitis limited to pleuropulmonary manifestations,possibly induced by endotoxin

AIMS: We investigated a rare case of small vessel vasculitis (SVV) limited to pleuropulmonary manifestations, possibly induced by endotoxin, to determine the activation of immuno-mediated cells and endothelia in the pleuropulmonary circulation. METHODS AND RESULTS: A 44-year-old man with a high fever was X-rayed, revealing bilateral pleural effusion and atelectasis in the chest. His laboratory data were within normal limits except for a high white blood cell count and a high C-reactive protein level. Autoantibodies including anti-neutrophil cytoplasmic antibody were negative. Endotoxin was detected in his sera, but repeated cultures of sputa, urine, blood and the pleural effusion were negative for bacteria. Video-assisted thoracic surgery was performed and lung and parietal pleura specimens were obtained. Histology showed arterioles or small arteries infiltrated by monocytes or neutrophils with fibrinoid necrosis and acute or chronic venulitis. A diagnosis of SVV in the lung and pleura was made. Immunohistochemistry revealed that interleukin (IL)-1beta was expressed in monocytes and vascular cell adhesion molecule (VCAM)-1 on endothelial cells in the vasculitic lesions in the lung. CONCLUSIONS: Endotoxin possibly induced the inflammation in this apparently unique case of pleuropulmonary small vessel vasculitis. Immunohistochemistry revealed the expression of IL-1beta and VCAM-1 which may have caused activation of monocytes and endothelial cells within the vasculitic lesions.     

Strong linkage disequilibrium of a HbE variant with the (AT)9(T)5 repeat in the BP1 binding site upstream of the β-globin gene in the Thai population

A binding site for the repressor protein BP1, which contains a tandem (AT)_x(T)_y repeat, is located approximately 530 bp 5 to the human -globin gene (HBB). There is accumulating evidence that BP1 binds to the (AT)₉(T)₅ allele more strongly than to other alleles, thereby reducing the expression of HBB. In this study, we investigated polymorphisms in the (AT)_x(T)_y repeat in 57 individuals living in Thailand, including three homozygotes for the hemoglobin E variant (HbE; 26Glu->Lys), 22 heterozygotes, and 32 normal homozygotes. We found that (AT)₉(T)₅ and (AT)₇(T)₇ alleles were predominant in the studied population and that the HbE variant is in strong linkage disequilibrium with the (AT)₉(T)₅ allele, which can explain why the ^E chain is inefficiently synthesized compared to the normal ^A chain. Moreover, the mildness of the HbE disease compared to other hemoglobinopathies in Thai may be due, in part, to the presence of the (AT)₉(T)₅ repeat on the HbE chromosome. In addition, a novel (AC)_n polymorphism adjacent to the (AT)_x(T)_y repeat (i.e., (AC)₃(AT)₇(T)₅) was found through the variation screening in this study.MIM and accession numbers and URLs for data presented herein are as follows: Online Mendelian Inheritance of Man (OMIM), (for HBB [MIM 141900]). GenBank, (accession number [NG_000007.2] reference sequence information).     

Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells

The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 x 10(9)PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8(+) T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8(-/-) mice, and partially blocked in CD4(-/-) mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity.     

Long‐term observation of a Japanese mucolipidosis IV patient with a novel homozygous p.F313del variant of MCOLN1

Mucolipidosis type IV (MLIV) is an autosomal recessively inherited lysosomal storage disorder characterized by progressive psychomotor delay and retinal degeneration that is associated with biallelic variants in the MCOLN1 gene. The gene, which is expressed in late endosomes and lysosomes of various tissue cells, encodes the transient receptor potential channel mucolipin 1 consisting of six transmembrane domains. Here, we described 14‐year follow‐up observation of a 4‐year‐old Japanese male MLIV patient with a novel homozygous in‐frame deletion variant p.(F313del), which was identified by whole‐exome sequencing analysis. Neurological examination revealed progressive psychomotor delay, and atrophy of the corpus callosum and cerebellum was observed on brain magnetic resonance images. Ophthalmologically, corneal clouding has remained unchanged during the follow‐up period, whereas optic nerve pallor and retinal degenerative changes exhibited progressive disease courses. Light‐adapted electroretinography was non‐recordable. Transmission electron microscopy of granulocytes revealed characteristic concentric multiple lamellar structures and an electron‐dense inclusion in lysosomes. The in‐frame deletion variant was located within the second transmembrane domain, which is of putative functional importance for channel properties.     

Terbutaline-induced triphasic changes in volume of rat alveolar type II cells: the role of cAMP

Changes in the volume of rat alveolar type II cells (AT-II cells) induced by terbutaline, a beta(2)-agonist, were measured using video-enhanced contrast microscopy. The changes consisted of three phases: initial cell shrinkage, cell swelling, and gradual cell shrinkage. The initial cell shrinkage was Ca(2+)-dependent and was inhibited by quinine (a K+ channel blocker). The subsequent cell swelling was cAMP-dependent and was inhibited by amiloride (a Na+ channel blocker). The final cell shrinkage was cAMP-dependent and was inhibited by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB, a Cl- channel blocker). Thus, terbutaline-induced cell volume changes were regulated by both Ca2+ and cAMP. Accumulation of cAMP alone, however, induced the Ca2+ -dependent cell shrinkage of AT-II cells and H-89 (a PKA inhibitor) inhibited terbutaline-induced cell volume changes. This suggests that cAMP accumulation stimulates the Ca2+ signal during terbutaline stimulation. In conclusion, terbutaline stimulates not only Na+ influx, but also K+ and Cl- release mediated via cAMP accumulation in rat AT-II cells, which induces the triphasic cell volume changes.     

Dosimetric properties of radiophotoluminescent glass rod detector in high-energy photon beams from a linear accelerator and cyber-knife

A fully automatic radiophotoluminescent glass rod dosimeter (GRD) system has recently become commercially available. This article discusses the dosimetric properties of the GRD including uniformity and reproducibility of signal, dose linearity, and energy and directional dependence in high-energy photon beams. In addition, energy response is measured in electron beams. The uniformity and reproducibility of the signal from 50 GRDs using a 60Co beam are both +/- 1.1% (one standard deviation). Good dose linearity of the GRD is maintained for doses ranging from 0.5 to 30 Gy, the lower and upper limits of this study, respectively. The GRD response is found to show little energy dependence in photon energies of a 60Co beam, 4 MV (TPR20(10)=0.617) and 10 MV (TPR(20)10=0.744) x-ray beams. However, the GRD responses for 9 MeV (mean energy, Ez = 3.6 MeV) and 16 MeV (Ez = 10.4 MeV) electron beams are 4%-5% lower than that for a 60Co beam in the beam quality dependence. The measured angular dependence of GRD, ranging from 0 degrees (along the long axis of GRD) to 120 degrees is within 1.5% for a 4 MV x-ray beam. As applications, a linear accelerator-based radiosurgery system and Cyber-Knife output factors are measured by a GRD and compared with those from various detectors including a p-type silicon diode detector, a diamond detector, and an ion chamber. It is found that the GRD is a very useful detector for small field dosimetry, in particular, below 10 mm circular fields.     

Immunocytochemical characteristics of human osteosarcoma cell line HS-Os-1: possible implication in apoptotic resistance against irradiation

In our previous study, we examined reactive oxygen species (ROS) formation in T lymphocytes following 5 Gy irradiation. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of the hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation. In the succeeding study, we examined radiation-induced ROS formation, oxidative DNA damage, early apoptotic changes, and mitochondrial membrane dysfunction in the human osteosarcoma cell line HS-Os-1. We found that ROS formation and oxidative DNA damage were actually scarcely seen after irradiation of up to 30 Gy in these cells, that mitochondrial membrane potential was preserved, and that apoptotic changes were not demonstrated despite the relatively high-dose irradiation of 30 Gy. In the present study, we examined the immunocytochemical characteristics of the apoptotic-resistance of the HS-Os-1 cell line against irradiation in order to clarify its possible implications regarding radiosensitivity. The results showed that these cells lack P53 and Bax protein expression, and strong peroxidase activity was confirmed in the nuclei of the cells. Moreover, SODII (manganese superoxide dismutase II) protein expression was gradually increased in spite of irradiation of up to 30 Gy. Therefore, it is concluded that HS-Os-1 cells are originally apoptotic-resistant and that the cells possess a strong ability to scavenge for free radicals. To convert these cells to a state of apoptotic-susceptibility, a powerful oxidant such as hydrogen peroxide might exert such an effect in terms of the production of hydroxyl radicals in lysosomes in the cells as shown in our previous studies. The origin of the radioresistance of the human osteosarcoma cell line HS-Os-1 is considered to to be low degree of ROS formation following irradiation, reflecting the strong scavenging ability of these cells for free radicals including hydroxyl radicals.     

Intramural sarcoma of the carotid artery with adventitial inflammation and fibrosis resembling 'inflammatory aneurysm'

A rare case Is descrlbed of an Intramural sarcoma of the rlght common carotld artery coexistlng wlth adventitial inflammation and flbrosls, resembllng 'inflammatory aneurysm', which was resected from a 33-yearold Japanese woman who had presented with a pulsatile mass on the rlght side of the anterior neck. Grossly, the wall of the carotld artery showed an intimal tear with dlssectlon of the medla filled with thrombus. A graylsh area, abutting directly onto the dlssected space and Involving the media and inner adventltia, was composed of a-smooth muscle actin-positive and desmln-negative polygonal and splndle cells with large bluntended nuclei and coarse granular chromatin arranged Into a well-organized Interlacing bundle pattern. This portlon was thus considered to represent lelomyosarcoma. White to yellow-tan fibrotic tissue present in the adventitial area consisted of extensive lamellar fibrosis wlth scattered focl of lymphoplasmacytlc aggregates and obliterated arteries, and lacked atypical spindle and polygonal cells. These changes accorded with the histopathologlcal findlngs hitherto described in cases of 'inflammatory aneurysm', which is known to almost exclusively involve the abdominal aorta. We conslder this case unique In that the leiomyosarcoma involved an artery other than the aorta, wlth an 'inflammatory aneurysm'-like reaction in the same she. The posslble relatlonship between these two condltions Is dlscussed.