Transforming growth factor J3 type II receptor (TGFpRII) mutation in gastric lymphoma without mutator phenotype

A new mutation in the serine-threonine klnase domain of the transforming growth factor β type II receptor (TGFpRII) was found in a case of diffuse, B cell non-Hodgkin's lymphoma of the stomach. A mfssense mutation (ACA to GCA, Thr to Ala) was detected In exon 5, and a wild type allele was also present. This Is the first naturally occurring mutation in the klnase domain of this gene identified in human primary lymphoma. The replication error at three loci was negative, and the poly A tract of exon 3, which is frequently a target of mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the stomach Is an addition to an expanding catalogue of tumors with TGFβRII alterations, and the biological sequelae of the change in the functional domain and the clinical characteristics of the patient in this study are intriguing.     

Translocation (1;22)(p36;q11.2) with concurrent del(22)(q11.2) resulted in homozygous deletion of <Emphasis Type="Italic">SNF5/INI1</Emphasis> in a newly established cell line derived from extrarenal rhabdoid tumor

Malignant rhabdoid tumor (MRT) is a highly malignant pediatric cancer, which arises in various sites such as the kidney, brain, and soft tissues. Cytogenetic studies have revealed alterations of 22q11 in MRT. Recently, deletions and mutations of the SNF5/INI1 locus in 22q11.2 have been reported in MRT, suggesting that SNF5/INI1 is a tumor suppressor gene for MRT. Here we report our molecular cytogenetic study for a newly established cell line from extrarenal MRT with t(1;22)(p36;q11.2). Consequently, the reciprocal translocation was associated with the interstitial deletion of a small segment including SNF5/INI1, and another, chromosome 22, showed terminal deletion, the breakpoint of which was located 70–80 kb centromeric to SNF5/INI1, resulting in homozygous deletion of SNF5/INI1 in this cell line.     

Expression of S-100 protein in intercalated duct cells of bovine pancreas

Although Mutoh et al. have found intercalated ducts in the pancreatic islets of avians, including the chicken, moorhen (Gallinula chloorpus), and Japanese quail (Coturnix coturnix japonica), and even demonstrated the functions of intercalated duct cells in pancreatic islets, to our knowledge, there have been only a few reports on the relationship between intercalated ducts and islets in mammalia. Accordingly, in this study, we investigated whether intercalated ducts are morphologically related to the islets of cattle, by using S-100 protein as a ductal cell marker for immunocytochemistry and examining the ultrastructure of intercalated ducts and islets electron-microscopically. The results revealed intercalated ducts that reacted positively for S-100 protein within and near islets, with approximately 12% of the islets having intercalated ducts in the vicinity and approximately 1.5% containing intercalated ducts within them. Ultrastructurally, intercalated ducts were also seem to be closely related to the islets. In conclusion, the results of the present study indicate that a close relationship exists between intercalated ducts and islets.     

Dissociation of interleukin-2 production from the cell activation in response to the mitogenic lectin in peripheral CD4+ T cells of LEC mutant rats.

We have recently shown that an exogenous gradient of interleukin-8 (IL-8) induces the transendothelial migration of neutrophils. Treatment of endothelium with the cytokines IL-1 or tumour necrosis factor (TNF) also causes neutrophil transmigration, and recent evidence suggests that this may be due to endogenous IL-8 produced by the endothelium. We have used specific chemotactic desensitization of neutrophils to investigate the role of IL-8 in transmigration through cytokine-activated endothelium. Preincubation of neutrophils with IL-8 reduced their chemotactic transmigration response to an IL-8 gradient by 81%, demonstrating desensitization. Transmigration in response to cytokine-activated endothelium was inhibited by 104% after IL-8 preincubation, thus tending to support the role of IL-8. However, preincubation with another neutrophil chemotactic factor N-formyl-methionyl-leucyl-phenylalanine (FMLP), which did not affect the IL-8, response, also inhibited transmigration, by 74%. This suggests that FMLP preincubation acts to inhibit a non-IL-8-dependent mechanism of transmigration through cytokine-activated endothelium. Chemotactic factor pretreatment of neutrophils did not reduce their adhesion to activated endothelium, but specifically blocked the transmigration step. We have therefore shown that chemotactic transmigration can be subjected to factor-specific desensitization, and have used this to provide evidence supporting a role for IL-8 in transmigration through cytokine-activated endothelium, as well as suggesting a further IL-8-independent mechanism. These data also provide a mechanism for the observed defect in accumulation of neutrophils at inflammatory sites when chemotactic factors are infused intravenously.     

Pituitary Folliculo-Stellate-Like Cells Stimulate Somatotroic Pituitary Tumor Growth in Nude Mice

A new cell line (TtT/GF) established from a murine pituitary thyrotropic tumor having characteristics similar to those of pituitary folliculo-stellate cell (FS cell) was implanted into nude mice together with cells from a rat pituitary somatotrophic tumor cell line (MtT/S) to determine whether the former enhances pituitary tumor growth. For as long as 2-3 mo after implantation, MtT/S cells implanted either alone or together with fibroblasts formed either no tumors or only very small tumors in the nude mice. In contrast all of the nude mice that had received MtT/S cells implanted together with TtT/GF cells developed large tumors. Furthermore, the mice bearing the MtT/S and TtT/GF implants showed a significantly higher body weight and serum growth hormone level than those bearing only MtT/S cells or a combination of MtT/S cells and fibroblasts. The TtT/GF cell line itself had no tumorigenicity during the experimental period. Therefore, the TtT/GF cell line as a model of FS cells enhanced pituitary endocrine cell tumor formation. Additionally, immunocytochemistry showed that TtT/GF cells positive for glial fibrillary acidic protein (GFAP) or S-100 protein were present in the parenchymatous tissue elements or connective tissue surrounding the tumor nests. In the parenchymatous tissue, the TtT/GF cells exhibited a stellate appearance and surrounded neighboring tumor cells with their long cell processes. These results suggest that TtT/GF cells can serve as a model for pituitary FS cells, and are capable of stimulating pituitary tumor growth either by modifying the microenvironment or producing growth factors.     

Interrelation between membrane transport and the contents of alkali metal cations in HeLa cells

The relation of membrane transport of alkali cations to their external concentrations or to their cellular contents was studied in HeLa cells. Chilling the cells at 0 degrees C reversed cell Na+ and K+ to a mirror image of the normal pattern. Upon rewarming to 37 degrees C the ouabain-sensitive Rb+ uptake became 2-fold faster than the control. A kinetic analysis revealed that the stimulation was due to an increase in the maximal rate of Rb+ uptake, Jmax. The increase in apparent Km was relatively small. The analysis also showed that the ouabain-sensitive cation transport system seemed to have two binding sites for Rb+. The stimulation of Rb+ uptake was related to an increase in cell Na+, and an addition of ouabain abolished such a relation. Net Na+ flux which was in the direction from inside the cells to the medium at hypernormal cell Na+ was iiincreased when cell Na+ ncreased. In contrast, net Na+ flux which was in the opposite direction in the presence of ovabain was reduced and became almost 0 at cell Na+ of 900 nmol/mg of protein. The Na+/Rb+ coupling ratio in the ouabain-sensitive cation transport was apparently less than 1 at nearly physiological cell Na+, but it approached 1.5 when cell Na+ was sufficiently high. The sum of cell K+ plus Rb+ varied inversely with cell Na+, and this relation was unaffected upon treatment with ouabain. When Rb+ uptake declined below 80% of the control, cell K+ plus Rb+ was reduced, however, 40% of the sum of cell cations was still preserved even after complete inhibition of the cation pumps by ouabain treatment of 2 hr. Interrelations of these results are discussed.     

Corticospinal projections from areas 4 and 6 in the raccoon

Summary The corticospinal projections from areas 4 and 6 were investigated in the raccoon using the horseradish peroxidase (HRP) retrograde tracing technique. Multiple injections of lectin bound HRP and HRP were made into either the cervical or lumbar cord in 7 anesthetized raccoons. Retrogradely labeled neurons were observed throughout a wide extent of areas 4 and 6a. The HRP positive cells were most numerous within the dorsal bank of the cruciate sulcus within area 4 and continued around the fundus to occupy the lateral two-thirds of the ventral bank of the cruciate sulcus within area 6a. No labeled cells were observed in the more medially located area 6a. Although the HRP positive cells observed following the lumbar cord injections were situated slightly more medial and caudal to those observed following the cervical cord injections, considerable overlap between the two projections was noted. The corticospinal projections arising from areas 4 and 6a in the raccoon largely correspond in location to the regions functionally defined as the primary motor cortex and the supplementary motor area, respectively.     

Case of postradiation osteosarcoma with a short latency period of 3 years

Osteosarcoma is one of the neoplasms that may occur following exposure to radiation. A case of osteosarcoma arising in the craniofacial bone with a short latency period of 3 years after radiotherapy for maxillary squamous cell carcinoma is described. A 64-year-old-man underwent right partial maxillectomy and chemoradiotherapy due to squamous cell carcinoma of his right maxillary sinus. Histologically, the tumor was composed of moderately differentiated squamous cell carcinoma with a component of spindle cell carcinoma. Three years later, osteosarcoma developed in the craniofacial bone within the irradiation field of the first tumor. Detailed histological examination demonstrated that there was no component of osteosarcoma in the first tumor or squamous cell carcinoma in the second tumor. Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy. In this case, osteosarcoma was possibly a radiation-induced osteosarcoma with a short latency period of 3 years.     

Mutation analysis of two Japanese patients with Fanconi-Bickel syndrome

Fanconi-Bickel syndrome (FBS), or glycogen storage disease type XI, is a rare autosomal recessive disorder characterized by hepatorenal glycogen accumulation, Fanconi nephropathy, and impaired utilization of glucose and galactose. Recently, this disease was elucidated to link mutations in the glucose transporter 2 (GLUT2) gene. Only three mutations in three FBS families have been reported. Therefore, it is important to elucidate mutations in the GLUT2 gene in FBS by answering the question of whether the syndrome is a single gene disease. In this report, we describe two patients in two unrelated families clinically diagnosed with FBS. No mutation in the entire protein coding region of the GLUT2 gene was detected in patient 1, which suggested that no mutation existed in the GLUT 2 gene, or that some mutations had affected the expression of the GLUT 2 gene. In patient 2, a novel homozygous nonsense mutation (W420X, Trp at codon 420 to stop codon) was detected. These results support the correlation between GLTU2 gene mutation and FBS syndrome. However, many patients must be analyzed to determine whether other genes are involved in FBS. Received: July 16, 1999 / Accepted: September 3, 1999