A primary lung carcinoma producing alpha-fetoprotein, carcinoembryonic antigen, and human chorionic gonadotropin. Immunohistochemical and biochemical studies

This article documents a patient with lung carcinoma that produced three oncofetal antigens including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (hCG). Serum AFP, CEA, and hCG-beta-subunit were extremely high--118,000 ng/ml, 133 ng/ml and 0.9 ng/ml, respectively. Immunohistochemical staining of these tumor markers revealed that these proteins were present in different cells. The pattern of lectin affinity electrophoresis of AFP resembled that of hepatocellular carcinoma. Also investigated was the reactivity of serum CEA to monoclonal antibodies against peptide or sugar moieties. Serum CEA values measured by antipeptide monoclonal antibodies were higher than those measured by antisugar monoclonal antibodies. The demonstration of AFP, CEA, and hCG in different tumor cells suggests that three genomes were not reactivated together in a cell, and the lung carcinoma probably consisted of at least three clones of cancer cells with different phenotypes.     

Expression of matrix metalloproteinase matrilysin (mmp-7) was induced by activated ki-ras via ap-1 activation in sw1417 colon cancer cells

The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metallo-proteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.     

A case of granulocyte-colony stimulating factor producing gastric cancer]

We report a case of granulocyte-colony stimulating factor producing gastric cancer with multiple liver metastases. A 68-year-old woman who complained of epigastralgia visited our hospital. Upper gastrointestinal endoscopic examination revealed a type-2 gastric cancer. The laboratory data at admission indicated leukocytosis (35,900/microl) and a high level of serum granulocyte-colony stimulating factor (61 pg/mg). Granulocyte-colony stimulating factor producing gastric cancer was diagnosed by immunohistochemistry of biopsy specimen. Since we detected multiple liver metastases, chemotherapy was performed. Granulocyte-colony stimulating factor-producing gastric cancer is relatively rare and we summarize previous reports.     

Effect of carbon dioxide and oxygen on endothelin production by cultured porcine cerebral endothelial cells

We have previously reported the production of endothelin, a potent vasoconstrictor peptide, by porcine cerebral microvessel endothelia and suggested its important role in the regulation of local blood flow within the brain. In our present study, radioimmunoassay with anti-porcine endothelin antiserum revealed that endothelin, produced by cerebral microvessel endothelia grown on a filter, is released mainly to the basement membrane side, not the vascular lumen side. This finding suggests that endothelin constricts arterioles locally where it is produced by endothelia. We also found that cerebral microvessel endothelia produce less endothelin under low oxygen pressure and more endothelin under low carbon dioxide pressure. Our results suggest that endothelin has a role in the regulation of cerebral blood flow in response to oxygen and carbon dioxide pressure.     

Role of p53 mutations in endocrine tumorigenesis: mutation detection by polymerase chain reaction-single strand conformation polymorphism.

To elucidate the molecular basis for endocrine tumorigenesis, p53 mutations in human endocrine tumors were analyzed by using polymerase chain reaction-single strand conformation polymorphism. Exons 5 through 10 of the p53 gene were studied in genomic DNAs from 134 primary endocrine tumors and 6 human endocrine cancer-derived cell lines. Mutations were detected and identified in 4 endocrine tumors, including one parathyroid adenoma and three thyroid carcinoma cell lines. The sites of these mutations were in exons 5 (codon 151 and 152) and 7 (codon 248 and 255). In all of three tumor cell lines, but not in a parathyroid adenoma, the normal allele encoding the p53 gene was lost. However, p53 mutations were not found in any other endocrine tumors or cell lines. Based upon these results, we concluded that the p53 gene may play a role in the tumorigenesis of a limited number of parathyroid adenoma and thyroid cancers, and that the p53 mutation with an allelic loss of the p53 gene is an important factor in malignant tumorigenesis of the thyroid gland.     

Bifrontal interhemispheric approach to aneurysms of the anterior communicating artery

The authors review their experience with the bifrontal interhemispheric approach in 603 cases of single anterior communicating artery (ACoA) aneurysms and describe the operative technique. With this approach, the olfactory tracts are dissected, and both A1 segments of the anterior cerebral arteries are identified subfrontally. The interhemispheric fissure is then dissected and A2 segments are followed from the distal portion toward the ACoA complex. Following the administration of a combination of mannitol, vitamin E, and dexamethasone, a temporary clip is placed on at least the dominant A1 segment prior to dissection of the aneurysm itself. Once the aneurysm has been completely freed from the surrounding structures, the neck is ligated and clipped. If the aneurysm ruptures during surgery, temporary clips are placed on both A1 and A2 segments bilaterally and the operation proceeds in a completely dry field. With this method, it is possible to occlude any of the intracranial vessels for up to 40 minutes within 100 minutes of drug administration. To prevent the possibility of rerupture and the development of vasospasm in the period before aneurysm surgery, the authors have adopted a policy of performing ultra-early operations within 48 hours of the onset of symptoms. Among the 257 cases operated on during the 9 years since 1975, one-fifth have been operated on within 48 hours of rupture, and the in-hospital mortality rate has been only 4.3% (11 cases). Follow-up studies have shown that 87% of the 246 surviving patients have returned to useful lives.     

A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia

Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia.