[Peripheral Pulmonary Artery Aneurysm with Internal Thoracic Artery-Pulmonary Artery Shunt].

An 82-year-old woman with past history of pulmonary nontuberculous mycobacterial infection complained of hemoptysis and was pointed out the strongly stained nodule in the middle lobe of the right lung on chest enhanced computed tomography (CT), which was suggested to be peripheral pulmonary artery aneurysm. Angiography of the right internal thoracic artery (RITA) revealed the peripheral pulmonary artery aneurysm with the shunt from the branch of the RITA, which was considered to be the cause of hemoptysis. Transcatheter arterial embolization was performed for the branch of the RITA 2 times, however, the hemoptysis recurred again after 5 months. Therefore, after the third embolization for the RITA, the right middle lobectomy with amputation of the shunt vessel was performed. The patient has been well without hemoptysis for one year and 6 months after the surgery.

Postmortem evaluation of neuromuscular damages more extensive than the surgical intervention area after iliac crest bone graft.

Several complications may occur following iliac bone grafting, one of the common sites for autologous bone harvesting. Of these, it is difficult to localize the damage in neurological complications due to the presence of several nerves in a similar distribution area with variations among individuals. To minimize these complications, conventional clinical anatomical studies using normal human cadavers have estimated the theoretical neurological damage area corresponding to the surgical intervention area. We report a case of neuromuscular damage in a 93-year-old woman who had an iliac crest defect after a bone graft, based on the virtual and physical dissections with histological confirmations.In this study, the patient was confirmed to have severe neuromuscular complications with major complications including a hernia protruding through the iliac defect. One of the two ilioinguinal nerves was extracted with the hernia sac through the iliac defect, and its distal part was completely damaged. The iliohypogastric nerve, which was far from the defect foramen, also showed remarkable fibrosis and demyelination, affected by the degeneration of the transversus abdominis muscles.The present anatomical findings show that the area of eventual neuromuscular damage should be estimated to larger than the conventionally predicted area of direct nerve damage, which is usually concomitant with the surgical intervention area.

Ultrastructural changes in the choriocapillaris of N-methyl-N-nitrosourea-induced retinal degeneration in C57BL/6 mice.

N-methyl-N-nitrosourea (MNU) is known to cause apoptosis of photoreceptor cells and changes in retinal pigment epithelium (RPE). However, the changes in choriocapillaris, which nourishes photoreceptor cells by diffusing tissue fluid through RPE, have not been reported in detail. Therefore, we studied the ultrastructural transformation in and around the choriocapillaris to characterize the interdependence between choriocapillaris and surrounding tissue components in a mouse model. Seven-week-old male C57BL/6 mice were given a single intraperitoneal injection of MNU (60 mg/kg of body weight). Perfusion-fixed eyeballs were examined chronologically using immunohistochemistry and electron microscopy until the photoreceptor cells were lost. Sequential ultrastructural changes were observed in photoreceptor cells, RPE, Bruch's membrane, choriocapillaris, and choroidal melanocytes after an MNU injection. The lumens of the choriocapillaris narrowed following dilation, and the vascular endothelium showed structural alterations. When the photoreceptor cells were completely lost, the choriocapillaris appeared to be in a recovery process. Our results suggest that transport abnormality through Bruch's membrane and structural changes in the choroid might have influenced the morphology of choriocapillaris. The thin wall of the choriocapillaris appears to be the cause of the vulnerability with its altered morphology.

Upper gastrointestinal pathophysiology due to mouse malaria Plasmodium berghei ANKA infection.

BACKGROUND: Epigastric pain, vomiting, and other gastrointestinal problems are among the most important symptoms of malaria infection as they suggest the possibility that the condition is serious. Pathophysiologies such as gastric mucosal changes and delayed gastric emptying have been reported in serious cases of malaria infection. However, it is unclear whether or not pathophysiological involvement of the upper gastrointestinal tract occurs in Plasmodium berghei ANKA (PbA)-infected mice. METHODS: PbA-infective Anopheles mosquitoes were used to infect mice via the natural route of infection. Fifteen PbA-C57BL/6 mice were used as a cerebral malaria model and the same numbers of PbA-BALB/c mice were used as a cerebral malaria-resistant model, and then we investigated the pathophysiological involvement of the stomach and small intestine. RESULTS: On day 8 post infection, six PbA-C57BL/6 mice showed cerebral malaria and nine others had uncomplicated infection. All the PbA-C57BL/6 mice on that same day showed severe weight loss with multiple, red gastric patches and changes to the course of the small intestine with villus goblet cell enlargement. In addition, cerebral malaria cases showed gastric gas retention with submucosal edema and small intestinal shortening. In PbA-BALB/c mice, overextension of the stomach and gas retention were evident from week 2 after PbA infection, as well as changes to the course of the small intestine and mesenteric thinning with fragility. CONCLUSIONS: We described the upper gastrointestinal pathophysiology representing new findings directly linked to malarial severity and subsequent death in PbA-infected mice as a mouse model of malaria infection.

Foxc2 influences alveolar epithelial cell differentiation during lung development.

FOXC2, a forkhead transcriptional factor, is a candidate gene for congenital heart diseases and lymphedema-distichiasis syndrome and yellow nail syndrome; however, there are no reports on Foxc2 and the development of the lung. We have identified lung abnormalities in Foxc2-knockout embryos during investigation of cardiac development. The aim of this study was to clarify the morphological characteristics during lung development using ICR-Foxc2 knockout lungs. Mutant fetuses at embryonic days 10.5-18.5 were obtained from mating of Foxc2+/- mice and then analyzed. Notably, Foxc2-knockout lungs appeared parenchymatous and much smaller than those of the wild-type littermates. In the Foxc2 knockout lungs, the capillary beds remained distant from the alveolar epithelium until the late stages, the number of type2 alveolar cells per alveolar progenitor cell was lower and the type1 alveolar cells were thicker in Foxc2 knockout mice. In contrast, Foxc2 expression was only detected in the mesenchyme of the lung buds at E10.5, and it disappeared at E11.5 in Foxc2-LacZ knockin mice. Furthermore, the expression of Lef1 was significantly inhibited in E11.5 lungs. All of these results suggest that the abnormalities in Foxc2 knockout mice may involve maldifferentiation of alveolar epithelial cells and capillary vessel endothelial-alveolar epithelial approach as well as lymph vessel malformation. This is the first report about relationship between Foxc2 and lung development. This animal model might provide an important clue for elucidating the mechanism of lung development and the cause of respiratory diseases.

[A CASE OF URETERAL ENDOMETRIOSIS].

A 49-year-old woman was admitted to our hospital due to macroscopic hematuria. Contrast-enhanced computed tomography revealed left hydronephrosis, a tumor at her left ureter, pseudoaneurysm and ovarian cystoma. Prior to the operation, the tumorous lesion was considered as left ureteral cancer without metastasis (cT4N0M0; stage IV). Left nephroureterectomy was performed. After the surgery, pathological examination revealed that this lesion was extrinsic endometriosis originating from the ureter.We here report this case of ureteral endometriosis that presented with atypical clinical findings along with a review of the literature.

Giant Cell Tumor of the Skull: Review of the Literature.

BACKGROUND: Giant cell tumors (GCTs) are rare in the skull. The present report describes a case with a primary GCT located in the temporal bone and reviews the relevant literature. We also propose a treatment strategy for GCT of the skull. CLINICAL PRESENTATION: A 41-year-old man presented with headache and auditory disturbance. Radiologic images showed a lytic expansive extradural lesion originating primarily from the right temporal bone and expanding into the middle cranial fossa and the infratemporal fossa. A biopsy specimen of the lesion was obtained from the external auditory meatus. Total removal was performed with temporal craniectomy, mandibular condylar process removal, tympanoplasty, and mastoidectomy. DISCUSSION: The rate of recurrence of GCTs is related to complete resection and location of the GCT rather than to the degree of invasiveness. Some of the mononuclear cells and stromal cells in GCT express receptor activator of nuclear factor κ-ß ligand (RANKL). Because inhibition of RANKL and bisphosphonate therapy might eliminate giant cells, this approach might be useful for recurrent or unresectable GCTs of the skull. CONCLUSIONS: Preoperative diagnosis by biopsy is important in determining the therapeutic strategy of GCTs. Complete resection is important to reduce the recurrence rate of GCTs in the skull.

Effects of protein tyrosine phosphatase-PEST are reversed by Akt in T cells.

T cell activation is regulated by a balance between phosphorylation and dephosphorylation that is under the control of kinases and phosphatases. Here, we examined the role of a non-receptor-type protein tyrosine phosphatase, PTP-PEST, using retrovirus-mediated gene transduction into murine T cells. Based on observations of vector markers (GFP or Thy1.1), exogenous PTP-PEST-positive CD4(+) T cells appeared within 2 days after gene transduction; the percentage of PTP-PEST-positive cells tended to decrease during a resting period in the presence of IL-2 over the next 2 days. These vector markers also showed much lower expression intensities, compared with control cells, suggesting a correlation between the percent reduction and the low marker expression intensity. A catalytically inactive PTP-PEST mutant also showed the same tendency, and stepwise deletion mutants gradually lost their ability to induce the above phenomenon. On the other hand, these PTP-PEST-transduced cells did not have an apoptotic phenotype. No difference in the total cell numbers was found in the wells of a culture plate containing VEC- and PTP-PEST-transduced T cells. Moreover, serine/threonine kinase Akt, but not the anti-apoptotic molecules Bcl-2 and Bcl-XL, reversed the phenotype induced by PTP-PEST. We discuss the novel mechanism by which Akt interferes with PTP-PEST.

Clinical history and colliquative myocytolysis are keys to the diagnosis of shoshin beriberi.

Cardiovascular beriberi presents as either the fulminant (Shoshin beriberi) or chronic form. Shoshin beriberi is a rare disease that may lead to a fatal outcome if the patient does not receive appropriate treatment. In the present report, we describe the case of a 66-year-old man presenting with leg edema and dyspnea at rest. Clinical presentations were nonalcoholic Shoshin beriberi and lactate accumulation; however, clinical improvement was observed after the administration of thiamine. His pretherapy thiamine level (2.1 µ g/dL) was consistent with a diagnosis of beriberi. Based on the findings of the present case, we believe that a diagnosis can be made in patients with a clinical history that is consistent with that of Shoshin beriberi, combined with low thiamine levels, lactate accumulation, and colliquative myocytolysis. Learning Objective. Shoshin beriberi is often misdiagnosed because of its rarity; a detailed clinical history and characteristic myocardial histopathology changes may be useful for making a definite diagnosis.

Vasohibin-2 modulates tumor onset in the gastrointestinal tract by normalizing tumor angiogenesis.

BACKGROUND: Vasohibin-2 (VASH2) has been identified as an endogenous and vascular endothelial growth factor (VEGF)-independent angiogenic factor that is highly expressed in tumor cells. In the present study, we aimed to determine whether pre-existing vascular changes can be used to predict tumor transformation as benign or malignant. We sought to characterize microvascular changes and tumor development in the intestinal tract of ApcMin/+ mice and ApcMin/+/Vash2-/- mice. METHODS: ApcMin/+ mice provide a unique orthotopic model for the development of spontaneous adenomatous polyposis and subsequent carcinomas, a phenomenon termed the adenoma-carcinoma sequence. ApcMin/+ mice were mated with Vash2-/- mice with a mixed C57BL/6 background and the resulting pups were screened for the Min mutation and for the Vash2-/- gene by PCR. Intestinal tumors from ApcMin/+ mice and ApcMin/+/Vash2-/- mice were removed and either frozen or epon-embedded for subsequent analyses. For 3-dimensional imaging using confocal laser-scanning microscopy and transmission electron microscopy, cryosections were made, and immunofluorescent staining for various markers was performed. RESULTS: We found that structural abnormalities in tumor vessels from benign tumors resembled those in malignant tumors. In addition, a novel angiogenic factor, vasohibin-2 (VASH2) protein, was detected around tumor blood vessels in late-stage adenomas and adenocarcinomas, but was absent from early-stage adenomas in ApcMin/+ mice. Tumors used to examine endogenous VASH2 (derived from CMT93 colon carcinomas) were less vascularized in Vash2-/- mice and were more regular than those seen in wild-type (WT) mice. In addition, tumors in Vash2-/- mice were smaller than those in WT mice. Furthermore, cross-breeding of mice homozygous for a deletion of Vash2 with mice heterozygous for the APC mutation resulted in animals that showed a significant decrease in the number of polyps in the small intestine. CONCLUSION: We propose that VASH2 may modulate the onset of tumors in the gastrointestinal tract by regulating tumor angiogenesis.

Morphological and functional characterization of non-alcoholic fatty liver disease induced by a methionine-choline-deficient diet in C57BL/6 mice.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), appears to be increasingly common worldwide. Its histopathology and the effects of nutrition on liver function have not been fully determined. AIM: To elucidate the cellular mechanisms of NAFLD induced by a methionine-choline-deficient (MCD) diet in mice. Particular focus was placed on the role of phagocytic cells. METHODS: Male C57BL/6 mice were fed an MCD diet for 30 weeks. A recovery model was also established wherein a normal control diet was provided for 2 weeks after a period of 8, 16, or 30 weeks. RESULTS: Mice fed the MCD diet for ≥ 2 weeks exhibited severe steatohepatitis with elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Steatohepatitis was accompanied by the infiltration of CD68-positive macrophages (Kupffer cells). The severity of steatohepatitis increased in the first 16 weeks but was seen to lessen by week 30. Fibrosis began to develop at 10 weeks and continued thereafter. Steatohepatitis and elevated serum hepatic enzyme concentrations returned to normal levels after switching the diet back to the control within the first 16 weeks, but fibrosis and CD68-positive macrophages remained. CONCLUSIONS: The histopathological changes and irreversible fibrosis seen in this model were caused by prolonged feeding of an MCD diet. These results were accompanied by changes in the activity of CD68-positive cells with temporary elevation of CCL-2, MMP-13, and MMP-9 levels, all of which may trigger early steatohepatitis and late fibrosis through phagocytosis-associated MMP induction.

Low-grade meningioma showing nearly equal density with spinal fluid on radiographic images.

A 61-year-old woman had an intracranial tumour that was located on the falx. Meningioma was suspected and the tumour rapidly grew over 1 year. It showed nearly equal density with spinal fluid showing almost no enhancement on radiographic images, like microcystic meningioma. Successful removal of the tumour was achieved. Histopathologically, the tumour was diagnosed as low-grade meningioma. The meningioma had variable sized microcysts and the appearance of solid area was meningothelial meningioma. This is a rare radiographic image for meningothelial meningioma.

Prognostic factors of synkinesis after Bell's palsy and Ramsay Hunt syndrome.

OBJECTIVE: This study evaluated the prognostic factors of synkinesis following Bell's palsy and Ramsay Hunt syndrome. METHODS: A total of 345 patients consisting of 309 cases of Bell's palsy and 36 cases of Ramsay Hunt syndrome were enrolled in our study. The following 13 factors were considered as candidate prognostic factors for the presence of synkinesis at 6 months from onset: age, sex, diagnosis, diabetes mellitus, initial onset or recurrence, electroneurography (ENoG), number of days from onset to first visit to our hospital, the lowest Yanagihara grading system score, the change in Yanagihara score after 1 month, otalgia, hearing loss, vertigo and taste disturbances. These factors were analyzed by logistic regression. RESULTS: Logistic regression analysis clarified the lowest Yanagihara score, the change in Yanagihara score after 1 month, and the ENoG value for a prognosis of synkinesis. The most predictive prognostic factor was the lowest Yanagihara score, and the adjusted odds ratio in the multivariate model was 11.415. As for other prognostic factors, the adjusted odds ratios ranged from 7.017 (ENoG value) to 8.310 (the change in Yanagihara score after 1 month). These findings were therefore considered as high risk factors for synkinesis. CONCLUSION: It is possible to predict synkinesis following Bell's palsy and Ramsay Hunt syndrome on the basis of clinical symptoms. The lowest Yanagihara score, and the change in Yanagihara score after 1 month, together with the ENoG value at the onset, were found to be especially important factors for predicting synkinesis following Bell's palsy and Ramsay Hunt syndrome.

Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats.

A single intravitreal injection of erythropoietin (EPO) (50 ng/eye) or phosphate-buffered saline was administered to 5-week-old Sprague-Dawley rats at the onset of diabetes mellitus (DM) to determine and evaluate the protective effect of EPO on retinal microvessels. DM was induced by an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Morphological changes in microvessels in flat retinal preparations were evaluated during the subsequent 4 weeks by three-dimensional imaging of all blood vessels stained with fluorescein isothiocyanate-conjugated tomato lectin, following immunofluorescence techniques. No marked differences were observed in the shape or density of retinal vessels and the number of retinal capillary branches of the four groups [control, EPO, DM, and DM/EPO] up to 4 weeks after STZ administration. We also observed unique type IV collagen-positive filamentous structures that lacked both cellular elements and blood circulation (lectin-/type IV+ acellular strands), suggesting regressed vessel remnants. The lectin-/type IV+ acellular strands were detected soon after the onset of DM in the diabetic rats, and the number of these structures increased in the DM group (P < 0.01). A single intravitreal injection of EPO caused a significant reduction in the number of lectin-/type IV+ acellular strands to levels observed in the control group. However, the lectin-/type IV+ acellular strands were observed in the central area of the retina near the optic disc in all four groups. Intravitreal injection of EPO resulted in downregulation of the EPO receptor, vascular endothelial growth factor (VEGF), and VEGF receptor at 4 weeks. We conclude that EPO may play a primary role against the progression of diabetic retinopathy by reducing blood vessel degeneration at a very early disease stage.

Formation of abdominal cerebrospinal fluid pseudocyst.

A 63-year-old man who underwent insertion of a lumboperitoneal shunt developed gait disturbance. He had undergone surgery for gastric cancer 7 years and for ileus 5 years previously. Head computed tomography (CT) revealed enlargement of the ventricles. Abdominal CT revealed a cyst in the abdominal region and the distal segment of the peritoneal shunt tube located within the cyst. Laparotomy revealed the cyst located between the small intestine, colon, and peritoneum. The anterior wall of the cyst was excised. The distal segment of the peritoneal shunt tube was replaced in the rectovesical pouch. Histological examination showed that the cyst wall consisted of inner fibrous tissue and outer fat tissue without epithelial lining, and invasion of lymphocytes. The diagnosis was pseudocyst. Only 29 cases of abdominal cerebrospinal fluid (CSF) pseudocysts have been reported in adults. Although the mechanism underlying the formation of abdominal pseudocyst remains to be clarified, several predisposing factors for cyst formation have been reported including changes in absorption of CSF due to inflammation or infection, peritoneal adhesions due to previous abdominal surgery, and increase in the protein content of the CSF. In our case, the medical history and histological features of the cyst wall indicated that formation of the abdominal pseudocyst was associated with previous surgery or inflammatory reaction.

Hypoglossal nerve schwannoma with intratumoral hemorrhage.

Intratumoral hemorrhage of hypoglossal schwannoma is very rare. A 37-year-old man was admitted to our hospital with severe headache and gait disturbance. Radiologic examination revealed subarachnoid hemorrhage and a well-circumscribed enhanced lesion compressing the medulla oblongata. Gross total removal of the intracranial tumor was performed. Histopathological examination revealed the characteristic features of a schwannoma. The tumor had several hemorrhagic areas and numerous hyalinized blood vessels. Although the mechanism of hemorrhage from schwannomas is unclear, it is hypothesized that tumor vessels showing focal sinusoidal dilatation and hyaline thickening of the walls lead to spontaneous thrombosis with consequent necrosis, and often hemorrhage.