Kaori Nishikawa

“Candidatus Helicobacter heilmannii” from a Cynomolgus Monkey Induces Gastric Mucosa-Associated Lymphoid Tissue Lymphomas in C57BL/6 Mice

ABSTRACT Both Helicobacter pylori and “Candidatus Helicobacter heilmannii” infections are associated with peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. However, good animal models of H. pylori clinical diseases are rare. In this study, we aimed to establish an animal model of “Candidatus Helicobacter heilmannii” gastric MALT lymphoma. We used a urease-positive gastric mucosal and mucus homogenate from a cynomolgus monkey maintained in C57BL/6 mouse stomachs. The bacterium in the homogenate was identified as “Candidatus Helicobacter heilmannii” based on a DNA sequence analysis of the 16S rRNA and urease genes. Mucosal and mucus homogenates were used to inoculate C57BL/6 mice, which were then examined for 24 months. We observed a gradual increase in the surface area of protrusive lesions in almost all infected C57BL/6 mouse fundic stomachs 6 months after infection. Light microscopic observations revealed an accumulation of B lymphocytes along with destruction of glandular elements and the presence of lymphoepithelial lesions consistent with low-grade MALT lymphomas. Electron microscopic observation revealed numerous “Candidatus Helicobacter heilmannii” bacilli in the fundic glandular lumen, the intracellular canaliculi, and the cytoplasm of intact cells, as well as damaged parietal cells. In conclusion, “Candidatus Helicobacter heilmannii” induced gastric MALT lymphomas in almost 100% of infected C57BL/6 mice after a 6-month period associated with the destruction of parietal cells.

Visceral fat thickness in overweight men correlates with alterations in serum fatty acid composition.

BACKGROUND We examined relationships between visceral fat amount and alterations in serum fatty acid composition, both of which represent critical factors in the development of metabolic syndrome. METHODS Correlations were analyzed between visceral fat thickness as measured by ultrasonography and proportions of individual fatty acids in 21 normal-weight and 24 overweight Japanese men. RESULTS Significant associations were identified in overweight subjects. Visceral fat thickness displayed positive correlations to levels of palmitic acid and saturated fatty acids (r=0.475, P<0.05 and r=0.545, P<0.01, respectively); and negative correlations to levels of linoleic acid and polyunsaturated fatty acids (r=-0.513, P<0.05 and r=-0.428, P<0.05, respectively). Visceral fat thickness was also correlated with estimated desaturase activities, with positive correlations to Delta9- and Delta6-desaturase activities and negative correlations to Delta5-desaturase activity (r=0.580, P<0.01, r=0.669, P<0.01 and r=-0.559, P<0.01, respectively). No significant associations were identified in normal-weight subjects. CONCLUSIONS Significant associations between visceral fat amount and alterations in serum fatty acid composition were identified, but only in overweight individuals.

Low concentrations of serum n-3 polyunsaturated fatty acids in non-alcoholic fatty liver disease patients with liver injury

Tomonori Kishino*, Hiroaki Ohnishi, Kouki Ohtsuka, Satsuki Matsushima, Tsuyoshi Urata, Keiko Watanebe, Yukihisa Honda, Yoshitake Mine, Motoko Matsumoto, Kaori Nishikawa, Hideaki Mori, Shin’ichi Takahashi, Hitoshi Ishida and Takashi Watanabe 1 Department of Laboratory Medicine, Kyorin University School of Medicine, Tokyo, Japan 2 Department of Clinical Laboratory, Kyorin University Hospital, Tokyo, Japan 3 The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan

Microcirculatory alteration in low-grade gastric mucosa-associated lymphoma by Helicobacter heilmannii infection: its relation to vascular endothelial growth factor and cyclooxygenase-2.

Background:  There are clinical reports that Helicobacter heilmannii, as well as Helicobacter pylori, has been clinically reported to cause gastric low‐grade mucosa‐associated lymphoid tissue‐type (MALT) lymphoma, although its precise mechanism remains to be clarified. Thus, the present study was undertaken to elucidate the alteration of the microcirculatory structure and the relation to angiogenetic factors in mice infected with H. heilmannii for 3 and 6 months.

Persistent increase in myofibroblasts in Helicobacter heilmannii-infected mice but not in Helicobacter pylori-infected Mongolian gerbils: colocalization of COX-2 and bFGF immunoreactivity

The clinical significance of Helicobacter heilmannii infection remains uncertain, owing to the lack of a specific detection method. Recently, we reported a marked increase in myofibroblasts in the early stage of Helicobacter pylori infection in Monglian gerbils.

Hepatocellular carcinoma containing sarcomatous lesions in a normal liver, accompanied by secondary Budd-Chiari syndrome

To the Editor: We experienced a huge tumor in an otherwise-intact liver of a 53-year-old woman without any known predisposing causes. The tumor was a moderately differentiated hepatocellular carcinoma (HCC), intermingled with sarcomatous lesions. HCC in this case was complicated by secondary Budd-Chiari syndrome (BCS). It is quite unusual that such events occur simultaneously in a patient, although the precise pathoetiological link among them remains unclear. The patient was admitted to Kyorin University Hospital complaining of abdominal distension. She had received a blood transfusion during labor at the age of 25, but had had no episode of liver damage. There was no history of alcohol abuse, exposure to chemical carcinogens, or any chronic liver diseases. On physical examination, a hard liver was palpable. Longitudinal dilated veins were visible on the abdominal wall. Laboratory examinations showed an elevated lactate dehydrogenase (LDH) level of 884 IU/L and a decreased hemoglobin value of 8.5 g/dL. Liver function tests remained within the normal limit. Hepatitis virus infection, including hepatitis B, C, or other possible viruses, was negative. HCC tumor markers such as -fetoprotein were also negative. Computed tomography revealed a huge hepatic mass in the right lobe with a mixed appearance of solid and cystic components. The solid regions were stained with contrast medium until the delayed phase of the image. Duplex Doppler ultrasonography demonstrated reversed flat flows in the right and middle hepatic veins, which reflected dysfunction of the venous outlet into the inferior vena cava (IVC) possibly due to the compression of the mass, while a normal flow was confirmed in the left hepatic vein toward the IVC. Intrahepatic collateral vessels were also recognized communicating between the middle and left hepatic veins. These findings on ultrasonography were compatible with those of BCS. However, no membranous obstruction was found in the IVC or hepatic veins. Tumor cytology revealed malignant cells with round to spindle nuclei. All these clinical data led us to suspect the mass could be a hepatic sarcoma, and a right lobectomy was performed. The tumor occupied 23 × 22 × 12 cm of the resected hepatic lobe of 36 × 23 × 15 cm (3875 g) and contained large hemorrhagic necrosis foci. Pathologic examination revealed that the tumor was primarily a moderately differentiated HCC. However, lesions of sarcomatous appearance were also observed sporadically. These lesions were composed mainly of marked pleomorphic cells, including bizarre multi-nucleated giant cells, and partly of spindle-shaped cells lacking mutual adherence, resembling so-called pleomorphic sarcoma and spindle cell sarcoma, respectively. Noncancerous liver tissue showed no signs of chronic liver diseases except that mild dilatation of the central veins were noted in Zone 3. When multiple recurrences were found in the liver 19 months later, serum liver function tests and tumor markers were again within the normal limit, including LDH and hemoglobin. All these clinicopathologic findings indicate that the HCC in the present case was of unknown etiology. Although the development of HCC is often associated with chronic liver diseases, as represented by liver cirrhosis, it is unusual that HCC develops when liver tissues are intact. However, we cannot exclude the possibility that an unknown virus infection at the time of blood transfusion at the age of 25 was responsible for the carcinogenesis. A sarcomatous appearance has been observed in 9.4% of HCC cases in an autopsy study and in 1.8% of surgically resected cases. It is noteworthy that most of these cases have been shown to be related to at least one of a number of factors including chronic liver diseases, hepatitis virus infection, or sarcomatous transformation of HCC due to anticancer therapy, none of which, however, were confirmed in the present case. In comparison with ordinary HCC, this type of tumor tends to show certain characteristics such as low or negative levels of serum tumor markers, huge mass including hemorrhagic necrosis, and poor prognosis with intrahepatic metastasis, as were found in the present case. Another remarkable feature of this case is that HCC was complicated by the presence of secondary BCS. Although primary BCS could be a carcinogenic cause of HCC, in this case, BCS was considered to be the consequence of HCC. Collateral vessels disappeared in the remaining left lobe after surgery, which also supports this view. Although HCC is a possible though rare cause of BCS, occurring in only 0.6 to 3.2% of all BCS cases, atypical features in HCC in the present case, or HCC containing sarcomatous lesions, may be related to the pathogenesis of BCS.

A case of primary sclerosing cholangitis treated with endoscopic balloon dilatation of the common bile duct.

胆嚢結石を合併し,繰り返す胆管・胆嚢炎に対して内視鏡下バルーン総胆管拡張術が有効であった原発性硬化性胆管炎(以下PSC)の1症例を経験したので報告する.症例は39歳男性.2年来繰り返す腹痛・発熱を主訴に来院した.胆石・胆嚢炎の診断にて治療していたが,1年後の腹部超音波検査にて肝内胆管に多発性の不整な拡張を認めたため,入院した.入院時肝機能検査は正常であったが,内視鏡的逆行性胆道造影では総胆管は全長にわたり狭窄しており,肝内胆管は不整に拡張していた.PSCを疑い腹腔鏡下肝生検を施行したところ,組織像はPSCに合致した所見を示していた.大腸内視鏡にて炎症性腸疾患の合併もあり,胆嚢結石及び胆管・胆嚢炎を合併したPSCと診断した.一旦外来管理としたが,胆管・胆嚢炎にて再入院した.入院後,内視鏡下にバルーン総胆管拡張術を2回施行した.その後胆管・胆嚢炎の発症はなく,現在外来通院中である.