Electron microscopic investigation of transplanted squamous cell carcinoma in nude mice

Extirpated specimens of a squamous cell carcinoma from a human thigh were transplanted to the subcutaneous tissue of nude mice. Fourteen days later, the transplanted tumor masses were, again, extirpated from the nude mice. The transplanted chimera of the squamous cell carcinoma as seen with the electron microscope resembled the tumor cells before transplantation. It is concluded that ultrastructural investigation of transplanted chimera from squamous cell carcinoma cases may be useful for examining the site of action and clinical effects of anticancer drugs on this kind of tumor.     

Molecular cloning and complete nucleotide sequence of the genome of Japanese encephalitis virus Beijing-1 strain

The genomic RNA of the Japanese encephalitis virus (JEV) Beijing-1 strain was reversely transcribed and the synthesized cDNA was molecularly cloned. Six continuous cDNA clones that cover the entire virus genome were established and sequenced to determine the complete nucleotide sequence of the JEV RNA. The precise genomic size was estimated as 10,965 bases long. With flanking 95 bases at the 5 and 583 bases at the 3 non-coding regions, one long open reading frame (ORF) was revealed encoding a virus polyprotein with 3,429 amino acid residues. Because of sequence homologies observed between JEV and other flaviviruses, the genome organization of JEV appears to be identical with other flaviviruses. Genetic variation detected among flavivirus genomes is consistent with the established serological relatedness between JEV and other members of flaviviruses. The secondary structure of the JEV genome is deduced and discussed concerning its involvement in genome replication.     

HEREDITARY HEMORRHAGIC TELANGIECTASIA WITH MALIGNANT LYMPHOMA An Autopsy Case

A 60-year-old Japanese woman was diagnosed at autopsy as having had hereditary hemorrhagic telangiectasia (HHT) associated with systemic hemangiomas. In her repoduction period, premenstrual epistaxis frequently occurred. At the age of 60, the patient died of malignant lymphoma. At autopsy, multiple telangiectatic spots were noted on the face, limbs and trunk. The paraaortic lymph nodes, which were enlarged and irregularly conglomerated, were histologically diagnosed as malignant lymphoma of the diffuse large cell type. Submucosal telangiectatic lesions were found in the gastrointestinal system from the oral cavity to the rectum. Cavernous hemangiomas were present in various visceral organs including the liver, spleen, small and large intestines, rectum, appendix, uterus, and jejunal and colonic mesenteries. There was an arteriovenous fistula in the left lung. Examination of her family pedigree showed that the patient had an autosomal dominant trait of inheritance. The pathogenesis of the systemic visceral hemangiomas observed in this patient was considered to be similar to that of hamartoma.     

Loss of the SEDL gene product (Sedlin) causes X‐linked spondyloepiphyseal dysplasia tarda: Identification of a molecular defect in a Japanese family

A 23‐year‐old man was diagnosed as having X‐linked spondyloepiphyseal dysplasia tarda (SEDT; MIM 313400) based on his disproportionately short trunk, short stature, characteristic radiological features of the spine (posterior hump, end plate sclerosis, and disc space narrowing) and the hips (short and thick femoral necks), and positive family history. This Japanese family was found to have an intragenic deletion flanking intron 2 and exon 3 of the SEDL gene that not only included the 5′ untranslated region but also the coding sequence for the first methionine through the 25th alanine. This mutation was present in the proband and his unaffected mother (a heterozygote), but not in an unaffected sister and an unaffected uncle. The nature of the mutation predicted that the SEDL protein (Sedlin) was not produced in the proband, indicating that loss of Sedlin caused SEDT. © 2001 Wiley‐Liss, Inc.     

Nuclear accumulation of beta-catenin in intestinal-type gastric carcinoma: correlation with early tumor invasion

Mutation of the adenomatous polyposis coli gene, which is known to be an early event in the carcinogenesis of intestinal-type gastric carcinoma, leads to accumulation of beta-catenin. In addition, beta-catenin has been found to activate down stream signaling molecules in the wingless/Wnt pathway. In this study, the clinical significance of nuclear accumulation of beta-catenin was evaluated in gastric carcinoma. Immunohistochemical staining showed nuclear localization in 16 (12%) of 139 (94 intestinal-type and 45 diffuse-type) gastric carcinomas, and all 16 lesions with nuclear staining were intestinal-type adenocarcinomas. Of the 16 cases, 15 were in the early clinical stage. In the remaining case, the lesion had invaded the subserosal layer and showed strong nuclear staining at the invasive front. In 14 of the 16 cases with nuclear localization, there were no abnormal mobility shifts detected using polymerase chain reaction-single strand conformational polymorphism analysis. This was confirmed using direct sequencing analysis, which revealed the wild-type sequence in the 12 cases tested. Nuclear accumulation of beta-catenin did not correlate with lymph node metastasis or 5-year survival. These findings suggest that high intranuclear levels of beta-catenin protein play an important role in early tumor growth and may function in initiation of invasive processes in intestinal-type gastric carcinoma.     

Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer

Prostate cancer is a major cause of cancer death among elderly men in America, Europe, and Japan. However, the molecular mechanism of carcinogenesis is not yet well characterized. Frequent loss of heterozygosity (LOH) on chromosome 10q was reported in prostate cancer, and a candidate tumor suppressor gene, PTEN, was isolated on chromosome band 10q23.3. To investigate the genetic alterations of PTEN, we examined 45 primary prostate cancer specimens. LOH at the PTEN locus was observed in two (11.1%) of 18 tumors. However, no mutations were observed in any of the primary prostate cancers. These data suggest that mutation of the PTEN gene does not play a major role in prostate carcinogenesis of Japanese patients. Received: February 6, 1998 / Accepted: July, 3, 1998     

Immunohistochemical study of neuron specific enolase and S-100 protein in Hirschsprung's disease

Summary The distribution of whole differentiated neurons in the intestines from 15 children with Hirschsprung's disease was investigated using neuron specific enolase (NSE) and the perineuronal elements were studied using S-100 protein immunostaining.In aganglionic segments, NSE immunoreactive ganglion cells and S-100 positive satellite cells were absent, but the hypertrophic nerve trunks did show a markedly positive NSE and S-100 immunoreactivity.Two different forms of aganglionic segment were present. One was the middle aganglionic segment of long segment aganglionosis which was almost completely dennervated. In the other type, there were several NSE positive nerve fibers in the muscularis propria of both the aganglionic segment of short segment aganglionosis and the distal aganglionic segment of long segment aganglionosis. These latter two aganglionic segments seemed to be innervated by extrinsic nerves.     

Usefulness of a stature-based standard of skinfold thickness,especially for short children

Skinfold thicknessess (SFT) were measured at ulnar, triceps, subscapular and suprailiac sites in 730 boys and 724 girls (age 3–12 years) whose stature ranged from 100 to 150 cm and whose weight was within ±20% of the average. Means and standard deviation (SD) were calculated after logarithmic transformation of the original skinfold readings to demonstrate stature-based standards of SFT in Japanese children. The means of SFT exhibited nadirs (boys/ girls: ulnar 5.1/5.9 mm, triceps 7.9/9.5 mm, subscapular 4.9/6.1 mm, suprailiac 4.5/6.2 mm) in subjects 110–115 cm tall except for ulnar SFT in girls. SFT values increased as children increased in stature. Standard deviations of SFT at the four sites in short children (staturte < mean ?1 SD) were estimated using the stature-based standard as well as an age-based standard. Susms of the SDs assessed by the age-based standard were significantly smaller than those assessed by the stature-based standard in boys (P < 0.05) and girls (P < 0.01) with short stature, suggesting that SFT in short children was falsely understimated by the age-based standard. Thus, the stature-based standard is beneficial for the assessment of SFT, especially in children whose stature is below the mean ?-1 SD. © 1995 Wiley-Liss, Inc.     

Intratumorous distribution of catecholaminergic clone cells of human neuroblastoma

Summary The intratumorous distribution of catecholaminergic clone cells in 23 human neuroblastomas was studied using Falck-Hillarp's method, and the findings compared with the catecholamine (CA) content within the tumour. All the specimens contained elements with CA fluorescence, and the pattern of fluorescence was classified from the distribution of CA-positive cells and neurofibrils, as diffuse cellular (DC); diffuse fibrillary (DF), sporadic (S), clustered (C), island-shaped (I), and bundled (B). The strength of CA fluorescence of both cellular and fibrillary elements correlated well with the CA content within the tumour. In addition, all tumours of urinary VMA-negative cases also contained significantly larger amounts of CA than other, non-functioning, tumours in the paediatric age group. The results of this study suggest that firstly, the ratio of CA-positive cells to CA-positive neuronal processes is proportionately higher in the poorly-differentiated neuroblastomas and that secondly, even tumours negative for urinary VMA or HVA might be polyclonal and contain catecholaminergic elements.This study was supported in part by a Research Grant from the Ministry of Education, Japan (No. 59570549)