Kazuaki Misugi

Evaluation of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mouse model for parkinsonism

We evaluated neurochemically, behaviorally, and neuropathologically the availability of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black (BL) mice as a model for Parkinsons disease. The dopamine and 3,4-dihydroxyphenyl acetic acid content in the striatum, measured by high-performance liquid chromatography with an electrochemical detector, decreased by 70% at 10 and 20 days after the withdrawal of MPTP (30 mg/kg, i.p. twice daily for 5 days). During these days, the mice showed a decrease in locomotor activity and exhibited akinesia in both pole and traction tests. Light microscopically, 44% of the MPTP-treated mice showed neuronal degeneration in the substantia nigra 1 month after the withdrawal (damaged group), and 56% showed no change (undamaged group). Morphometric analysis revealed that the number of neurons in the substantia nigra decreased by 33% on the average in both groups. Electron microscopically, an electron-dense degeneration of most neurons was seen in the substantia nigra of the damaged group, and even in the undamaged group, loss of rough endoplasmic reticulum and mitochondrial deformity were seen in 50-70% of the neurons. Electron-dense bodies were seen in the striatum of both groups. These results show the validity of the MPTP-treated C57 BL mice as a suitable model for parkinsonism, including Parkinsons disease.

Peripheral neuroectodermal tumors of the chest wall in childhood.

A retrospective review of primary chest wall malignant tumors of childhood collected at the Childrens Memorial Hospital of Chicago was undertaken. Among twelve instances of poorly differentiated neoplasms whose uniform, montonous structure made accurate classification difficult or impossible by conventional histologic study, there were three tumors with features suggestive of neuroectodermal differentiation. Electron microscopic and immunohistologic findings further strengthened this interpretation, despite the fact that none of the patients had evidence of a primary neuroblastoma outside the chest wall. These results and a review of the pertinent literature support the conclusion that neuroectodermal neoplasms in childhood may present in peripheral somatic tissues with greater frequency than is commonly assumed. This importance of this distinction is discussed, particularly the need to distinguish these neoplasms from Ewings sarcoma.

Expression of matrilysin in vascular endothelial cells adjacent to matrilysin-producing tumors

Matrilysin is believed to play important roles in tumor progression and metastasis. In the present study, we analyzed matrilysin‐producing cells in various human cancer tissues by immunohistochemistry and in situ hybridization. Tumor cells in colorectal carcinomas, pancreatic carcinomas, transitional‐cell carcinomas of the kidney and small‐cell lung carcinomas were frequently positive for matrilysin. In addition, we found that endothelial cells of arterioles and venules adjacent to matrilysin‐positive tumors expressed matrilysin mRNA and protein. The endothelial cells adjacent to matrilysin‐negative tumors and those in normal tissues were negative for matrilysin. Furthermore, analyses by casein zymography, Western blotting and RT‐PCR showed that matrilysin was weakly expressed by cultured human umbilical vein endothelial cells. Our results suggest that the expression of matrilysin in vascular endothelial cells and in tumor cells may be regulated by common soluble factors, and that endothelial cell‐derived matrilysin may contribute to tumor angiogenesis and tumor metastasis. Int. J. Cancer 72:441–445, 1997.

Interdigitating Dendritic Cell Sarcoma of the Spleen: Report of a Case With a Review of the Literature

Interdigitating dendritic cell sarcoma is an extremely rare neoplasm that mainly occurs in the lymph nodes. We report a case of interdigitating dendritic cell sarcoma arising from the spleen, a previously unreported site for interdigitating dendritic cell sarcoma. An 87-year-old woman, visiting Ashigara Hospital with complaints of palpitation and dyspnea, was found to have pancytopenia and low proteinemia. Abdominal ultrasonography and CT scanning demonstrated severe splenomegaly with heterogeneous enhancement. She received a splenectomy under the clinical diagnosis of a splenic tumor. Grossly, the spleen was markedly enlarged, with confluent massive nodules. Microscopically, the normal architecture was effaced with diffuse proliferation of large pleomorphic cells arrayed in a somewhat sheet-like pattern. Erythrophagocytosis was commonly observed. Immunohistochemical studies showed that the tumor cells were positive for S-100 protein, fascin, vimentin, and CD68, but uniformly negative for CD45, B- and T-cell markers, CD1a, CD30, complement receptors, CD34, Factor VIII, HMB-45, and lysozyme. Ultrastructurally, the tumor cells possessed complex interdigitating cytoplasmic dendritic processes. Birbeck granules were absent. Based on these findings, the present case was diagnosed as interdigitating dendritic cell sarcoma. The patient died of multiple liver metastases 3 months postoperatively.

Specific expression of PP5/TFPI-2 mRNA by syncytiotrophoblasts in human placenta as revealed by in situ hybridization

Placental protein 5 (PP5) is a placenta-derived glycoprotein with serine proteinase-inhibiting activity. To date its physiological functions have not been well elucidated. Recently, cDNA sequence analysis revealed that PP5 belongs to the Kunitz-type proteinase inhibitor family and it is identical to tissue factor pathway inhibitor-2 (TFPI-2), homologous to TFPI. Northern blot analysis demonstrated that placental tissue is extremely rich in the transcripts. This study localized PP5/TFPI-2 mRNA in placental tissues at three different gestational periods using in situ hybridization. PP5/TFPI-2 mRNA was specifically detected in syncytiotrophoblast at any gestational period examined, suggesting that syncytiotrophoblast is the principal production site of PP5/TFPI-2 in developing placental tissues. This mRNA expression pattern of PP5/TFPI-2 is quite different from that of TFPI, which is mainly found in vascular endothelial cells. The results indicated possible roles of PP5/TFPI-2 in the trophoblast differentiation and in the maintenance of intervillous blood flow. Also, Northern analysis demonstrated no or little expression of PP5/TFPI-2 in four choriocarcinoma cell lines, in contrast to its abundant expression in syncytiotrophoblast.

Stimulation of cellular growth and adhesion to fibronectin and vitronectin in culture and tumorigenicity in nude mice by overexpression of trypsinogen in human gastric cancer cells

It has previously been reported that the trypsinogen gene is expressed in various human cancers. To inves-tigate the possible role of trypsin in tumor malignancy, trypsinogen-1 cDNA was introduced into the human gastric carcinoma cell line MKN-1. The overexpression of trypsinogen-1 in MKN-1 cells stimulated cellular growth and adhesion to fibronectin and vitronectin when the trypsinogen activator enterokinase was added into the culture. Enterokinase treatment of the conditioned medium of the MKN-1 transfectants partially converted the proforms of gelatinases B and A to their apparent active forms. When the MKN-1 transfec-tants expressing trypsinogen-1 were intraperitoneally transplanted into nude mice, the mice frequently produced tumors in the colon, spleen and liver. However, the mice implanted with control MKN-1 cells produced no tumors. These results strongly suggest that tumor-derived trypsin contributes to the dissemi-nated growth of some types of cancer cells including gastric cancer. ©Lippincott Williams & Wilkins

APPENDICEAL ENDOMETRIOSIS IN PREGNANCY

A 25‐year old woman at the 26th week of gestation underwent surgery for possible acute appendicitis. Pathological examination of the appendix showed extensive decidual change through the entire wall with perforation and surrounding acute inflammatory cell infiltration. To our knowledge, the present report is the second case of appendiceal endometriosis with this rare complication in the literature. The previously reported cases of appendiceal endometriosis which manifested clinically during pregnancy are briefly reviewed. ACTA PATHOL. JPN. 37: 1685.1690. 1987.

A neuropathologic study of Werdnig-Hoffmann disease with special reference to the thalamus and posterior roots

SummaryThe brains of five cases of severe infantile from of Werdnig-Hoffmann (W-H) disease were studied to observe the pathologic changes of sensory neurons and the thalamus. The present study disclosed severe cell loss, chromatolytic degeneration, and empty cell beds of the spinal anterior horn and cranial motoneurons (V, VII, X, XII). Glial bundles were also noted in the anterior roots. In the sensory systems, glial bundles in the posterior roots (2/5), ghost cells in Clarkes column (2/5), and degeneration of the thalamus, mainly in the lateral formation (4/4) were noted. It was demonstrated that not only degeneration of lower motor neurons and glial bundles in the anterior roots, but also degeneration of sensory neurons and thalamus were present in W-H disease. These findings suggested the possibility that W-H disease is a multisystemic disease involving both the anterior and posterior root systems. No sensory involvement was found clinically. Characteristic wrist drop was observed in four cases, two of which also having motor nerve conduction velocity (MCV) delay. On the other hand, MCV of another case without wrist drop was normal. The possibility that wrist drop might be one of the clinical features of peripheral nerve dysfunction was discussed, but further pathologic evaluation of peripheral nerves is needed.

Hepatitis B surface antigen positive hepatocellular carcinoma in children: Report of a case and review of the literature

This report describes a case of adult type hepatocellular carcinoma (HCC) of a ten‐year‐old boy. The liver showed no cirrhosis but hepatitis B surface antigen (HBs‐antigen) was demonstrated in the nonneoplastic liver cells. Serological examination of his family revealed positive HBs‐antigen of the patients mother suggesting familial transmission to the patient in his early life. Histologic demonstration of HBs‐antigen was performed on 36 adult HCC cases and 14 childhood cases including three HCC and eleven hepatoblastoma. HBs‐antigen was demonstrated in 12 adult cases, one of which showed no cirrhosis. All childhood cases except for the one presented here showed no HBs‐antigen. Review of the literature disclosed four other cases of HBs‐antigen positive HCC in children. The present case is unique in that the non‐neoplastic portion of the liver showed neither hepatitic nor cirrhotic manifestations. These HBs‐antigen positive HCC in childhood may imply the significant relationship between HB virus and HCC not only in adult but also in childhood.

Von Hippel-Lindau tumour suppressor gene. Localization of expression by in situ hybridization.

Inactivation of the von Hippel–Lindau (VHL) tumour suppressor gene is responsible not only for VHL disease, but also for sporadic renal cell carcinoma and cerebellar haemangioblastoma. The distribution of VHL gene expression in the mouse embryo was recently studied by in situ hybridization, along with human VHL in 14‐week‐old fetal kidney: there was widely distributed expression in the former and expression in the tubules and blastema in the latter. Adult human tissue and other fetal organs were not examined. The present paper describes an in situ hybridization study to assess the function of the VHL gene in adult human tissues and in tissues of human fetus at 28 weeks of gestation. The expression of the VHL gene was limited to the adult and fetal brain and kidney, and the adult prostate. Nerve cells in adult and fetal brain were positive, including the cerebellar Purkinje cells. In adult and fetal kidney, the proximal tubular epithelium, the putative origin of the common type of renal cell carcinoma, showed intense signal, whereas the distal nephron, glomeruli, and nephrogenic blastema showed no significant signal. The prostate showed significant signal in the basal epithelium. The adrenal, pancreas, and epidydimis showed no significant signal, in spite of the frequent occurrence at these sites of neoplastic or hamartomatous lesions in VHL disease.