Kiyoshi Aita

Plexiform angiomyxoid myofibroblastic tumor of the stomach.

We report 2 cases of plexiform angiomyxoid myofibroblastic tumor of the stomach, a tumor entity that has not been described previously. The patients were a 50-year-old man (case 1) and a 68-year-old man (case 2). In case 1, the patient presented with acute abdominal pain. The tumor in case 2 was incidentally found at laparoscopic cholecystectomy. Grossly, the tumors were 4.0 cm (case 1) and 4.5 cm (case 2) in their greatest dimension, and they were recognized as submucosal tumors. The tumor caused gastric perforation in case 1. Histologically, the tumors extended from the serosa to the submucosa of the gastric wall, showing a plexiform growth pattern. Bland spindle tumor cells were observed, and they were separated by abundant intercellular myxoid matrix. The stroma was rich in small vessels. Immunohistochemically, the tumor cells were positive for α-smooth muscle actin and muscle actin, and negative for KIT, CD34, and S-100 protein. Electron microscopic findings were consistent with the myofibroblastic nature of the tumor cells. No mutations were found in the c-kit and platelet-derived growth factor receptor alpha genes. Although clinical follow-up data were insufficient, the histologic appearances suggested the benign nature of the tumors. However, the tumor in case 1 caused gastric perforation and necessitated an emergency operation.

Herpes simplex virus hepatitis in macrophage-depleted mice: the role of massive, apoptotic cell death in pathogenesis.

Infection with herpes simplex virus or hepatitis viruses can lead to fulminant hepatitis, but there is controversy about the underlying conditions needed for such disease. To investigate how the impairment of host defences might be involved, macrophages were depleted by administration of silica to mice before intravenous injection with herpes simplex virus type 1 (HSV-1). Such mice died rapidly and their livers were yellowish and shrunken (acute yellow atrophy), and occasionally grossly haemorrhagic. Small foci of apoptotic cells developed in the liver lobules; these rapidly became confluent and zonal over time. The overall lesion pattern was similar to massive hepatic necrosis, and there was extensive HSV replication in the liver lesions. In the liver, DNA fragmentation characteristic of apoptosis followed the time course of HSV-1 propagation. These findings suggest that one of the underlying conditions for fulminant viral hepatitis may be inadequate macrophage response, and that the massive hepatic damage, often defined as cell necrosis, may actually be apoptosis of liver cells subsequent to virus infection.

Solid pseudopapillary tumor of the pancreas with metastases to the lung and liver

Presented herein is the case of a 41‐year‐old woman who was admitted to Teikyo University Hospital with abdominal and back pain. Clinical examination revealed a large mass of the pancreas and multiple nodules in the liver. After surgical resection of the pancreatic and liver tumors, liver nodules recurred repeatedly, and a solitary mass lesion occurred in the right lung. Grossly, the pancreatic tumor was large and partially cystic. Histologically, small and uniform tumor cells proliferated, having solid and pseudopapillary patterns. These pathological findings enabled a pathological diagnosis of solid pseudopapillary tumor (SPT) of the pancreas to be made. The pathological appearance of the liver and lung tumors was similar to that of the pancreatic tumor. This is the first report of a case of pancreatic SPT that showed lung metastasis. It should be kept in mind that pancreatic SPT may take such an aggressive clinical course, although they are usually benign in nature.

Acute adrenal infection by HSV-1: role of apoptosis in viral replication

Summary. Replication of herpes simplex virus type 1 (HSV-1) in the adrenal gland of mice was observed 12 h after intravenous inoculation, peaked at 48 h (7 × 107 PFU/tissue), and was maintained until death. Virus spread to the bilateral intermediolateral column of the thoracic spinal cord. Infected cells appeared in the fascicular zone of the adrenal cortex 12 h after infection, and cell death was evident in lesions found in the adrenal cortex. Lesions involved the medulla 48 h after inoculation. In cortical lesions, cell nuclei were fragmented or shrunken with little damage to the cytoplasm. DNA fragmentation appeared 12 h after inoculation and increased mainly in cortical lesions, which were characterized by apoptosis induced by HSV-1 infection. In the adrenal medulla, cells were fused and formed multinucleated giant cells but rarely displayed cell death. Macrophages, which serve as a frontal barrier to viral infection in the adrenal gland, especially the cortex, were fewer in number than those found in the liver or spleen. It is likely that HSV-1 easily infects the adrenal gland, resulting in suppression of local immunity, and that adrenal cell apoptosis serves as a primitive type of immunity to limit viral replication.

Streptococcal and staphylococcal superantigen-induced lymphocytic arteritis in a local type experimental model: Comparison with acute vasculitis in the arthus reaction

Many pathogenic bacteria produce superantigenic exotoxins. To study their pathogenetic role, in particular to test whether these toxins are able to induce vasculitis, we developed a local-type experimental model in rabbits. Toxins were injected along the intermediate auricular artery of the ear. The histology of ear skin, including the artery, was examined after single or repeated injections. Repeated injections of streptococcal erythrogenic toxins produced chronic-type arteritis characteristic of lymphocytic infiltration, whereas single injection induced no acute-type vasculitis. Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 also induced the same type of arteritis, although weaker in degree. In human patients these lesions are similar to those of Kawasaki disease, a systemic vasculitis with unknown etiology. The Arthus reaction to human serum albumin in immunized rabbits included acute-type vasculitis similar to polyarteritis nodosa when examined in this model. Microvasculitis lesions similar to leukoclastic vasculitis were combined in the Arthus reaction but not in the superantigen-induced lesions. Our experimental model described here is widely applicable to the study of the etiology and pathogenesis of human diseases involving vasculitis lesions.

Hepatitis B and C virus infection and p53 mutations in human hepatocellular carcinoma in Harbin, Heilongjian Province, China

To clarify the importance of hepatitis B (HBV) and C virus (HCV) infection and p53 gene mutation in the genesis of hepatocellular carcinoma (HCC), we investigated DNA samples of formalin-fixed paraffin-embedded HCC tissue specimens from patients in the North China area of Harbin, Heilongjian province. Fifty-eight DNA samples from 43 cases obtained during surgery and the remaining 15 autopsy materials were analyzed by polymerase chain reaction (PCR) about HBV and HCV. The p53 gene (exon 7) mutant testing, in addition, was performed by PCR-direct sequencing. Histopathologically, we determined the histological grade of HCC in all specimens. Forty-five (77.6%) of 58 cases were HBV DNA-positive; only two (3.4%) HCV RNA-positive cases were found. Two of 37 samples screened showed a point mutation (AGG to AGT) at codon 249, the exon 7 hot spot of the p53 gene. The fact implies that HBV plays a very important role, but aflatoxin B1 is not an important factor in the genesis of HCC in Harbin, Heilongjian district, Peoples Republic of China.

The Role of Donor CD4+ T Cells in the Reconstitution of Oral Immunity by Herpes Simplex Virus Type 1 in Severe Combined Immunodeficiency Mice

Severe combined immunodeficiency (SCID) mice with ill-developed Peyers patches develop neither antibodies nor protection against lethal herpes simplex virus type 1 (HSV-1) infection by oral immunization. However, SCID mice carrying spleen cells from immunocompetent BALB/c mice had serum anti--HSV-1 antibody; anti--HSV-1 IgA antibody was detected in eye wash samples, and the mice were protected against lethal HSV-1 infection (88% survival rate). Western blotting showed that antibodies in SCID mice carrying spleen cells from BALB/c mice recognized 60-kDa HSV-1. The effector cells in transferred spleen cells were CD4(+), not CD8(+), T cells. Donor T cells were detected in the submucosal layer of the gut in SCID mice 1 day after transfer. Rapid movement of donor T cells to the gut may have a role in mucosal immunity to HSV-1. Thus, the normal environment for mucosal immunity develops in SCID mice without prior presence of CD4(+) T cells.

Herpes simplex virus types 1 and 2 infect the mouse pituitary gland and induce apoptotic cell death

Summary.Herpes simplex virus (HSV) infected the anterior lobe of the pituitary gland resulting in cytopathic changes following intravenous (i.v.) inoculation of male mice. Both HSV type 1 (HSV-1) and type 2 (HSV-2) were isolated from pituitary gland following i.v. infection, but not after intraperitoneal inoculation. HSV-infected pituitary cells were microscopically visible beginning at 24 h or 48 h following i.v. inoculation and were localized in the anterior pituitary. In both HSV-1 and -2 infections the pituitary lesions were apoptotic, as determined by light and electron microscopy, TUNEL, and DNA gel electrophoresis. However, the pituitary infection does not appear to be life-threatening since pituitary lesions were also observed following i.v. infection with HSV-1 strain −GC which possesses low virulence. These results suggest that the pituitary gland is one of the target organs of HSV infection.

A 76‐year‐old man who developed febrile unconsciousness with magnetic resonance imaging findings indicating encephalitis

On 24 April 2002, a 76-year-old man who had suffered acute hepatitis during his childhood underwent a medical examination that revealed abnormal liver function. Two days later, he consulted a doctor at the Hospital of Teikyo University School of Medicine; his serum AST was 1468 IU/L, ALT 1232 IU/L, g-GTP 316 IU/L, ALP 510 IU/ L, total bilirubin 2.7 mg/dL, and direct bilirubin 1.7 mg/dL. He was admitted to the Hospital on the same day. The patient was alert, and he was jaundiced without edema. His pulse rate was 72/min. Neither his liver nor spleen were palpable. On 11 May, he developed nasal bleeding. Because the plasma prothrombin time (%) was low (32%), a pulse therapy with methyl prednisolone was started. Three days later, he developed hepatic encephalopathy, grade II, with a diagnosis of subacute fulminant hepatitis. Disseminated intravascular coagulopathy also occurred. Plasma exchange was done from 15 May to 24 May, with the patient becoming alert on 23 May. On the evening of 10 June 2002, a high fever (39.2∞C) and abnormal behavior with mild consciousness disturbance (Japan Coma Scale I-2) developed. An EEG on 10 June revealed spike-and-wave complexes in the left cerebral hemisphere, and diffusion-weighted MRI of the head demonstrated high-intensity lesions essentially confined to the bilateral insular cortex (Fig. 1). With these findings combined, a diagnosis of encephalitis was made, although the lumbar puncture could not be performed because of the bleeding tendency. In spite of immediately started acyclovir, the patient’s condition deteriorated rapidly, resulting in deep coma on 14 June. He died on 20 June, only 10 days after the onset of symptoms of encephalitis. The laboratory examination showed that hepatitis A IgM antibody and antigen, hepatitis C virus RNA, Epstein–Barr virus antibody, and cytomegalovirus antibody were negative.

Herpes encephalitis complicated during the recovery stage of fluminant hepatitis

劇症肝炎回復期のステロイド減量中にヘルペス脳炎を発病し死亡した1例を経験した. 症例は76歳の男性. 2002年4月23日より鼻漏が出現し, 翌日近医を受診して肝障害を指摘された. 4月26日, 当院に入院となった. 服薬歴と好酸球増多, DLST陽性で, 薬物性肝障害と診断した. 入院19日目に劇症肝炎亜急性型と診断し, ステロイドパルス療法に加え, 血漿交換・血液濾過透析を施行した. 入院44日目にはPT, 意識ともに改善傾向であった. 入院45日目に38度台の発熱と異常行動が出現し, brain MRI, 脳波にてヘルペス脳炎と診断. 直ちにアシクロビルを投与するも, 脳炎にて死亡した. 剖検にて, 脳組織よりHSV-1 DNAが検出された. 肝不全状態に加え, ステロイド治療を行うような状態では, ヘルペス脳炎等の重症ウイルス感染症の発症も念頭において, 迅速に対応する必要があると考えられた.