Mechanism of carcinogenesis in familial tumors

It is thought that malignant tumors occur through interactions of multiple environmental factors and a personal genetic factor. A normal somatic cell having an intrinsic function is able to acquire the characteristics of a malignant cell under the influence of many factors. A small percentage of all tumors have obvious familial aggregation. These entities are called familial cancer. The familial cancer syndrome is well defined for colorectal cancer, breast cancer, endocrine neoplasia, and so on. Traits of familial tumors are sequentially inherited by offspring through gametes in a Mendelian fashion, most commonly in an autosomal-dominant manner. Carcinogenesis requires multiple genetic events. A patient with a familial tumor is ahead of an individual without any germline mutation in the carcinogenesis process. In such a situation, patients frequently suffer from multiple malignant tumors at a young age. It is well known that three major genes are closely related to the cell cycle and tumorigenesis. These gene types are protooncogenes, tumor suppressor genes, and DNA mismatch repair genes. Proto-oncogenes function to accelerate cells during the G₁ or growth phase of the cell cycle. Tumor suppressor genes act as blocks against cell growth and proliferation. Inactivation of tumor suppressor genes requires alterations in both alleles. These phenomena are known as Knudsons two-hits theory. However, DNA mismatch repair genes are known as caretaker genes and correct mismatch pair generation during DNA replication. Germline mutation of DNA mismatch repair genes causes hereditary nonpolyposis colorectal cancer. The tumor phenotype from patients with hereditary nonpolyposis colorectal cancer is demonstrated to be microsatellite instability positive.     

The diagnosis of lung cancer using 1064-nm excited near-infrared multichannel Raman spectroscopy

PURPOSE: Raman spectroscopy is based on Raman scattering of light from molecules. Because the wavelength of Raman scattered light depends on molecular composition, Raman spectra provide highly useful information about molecular composition. It has already been shown that Raman spectroscopy is potentially useful for the clinical diagnosis of malignant tumors. However, this technique had never been applied to the diagnosis of lung cancers, primarily because of interference from the strong fluorescence emitted from lung tissues. Our purpose was to examine the effectiveness of near-infrared Raman spectroscopy for the diagnosis of lung cancers. METHODS: We constructed a new near-infrared multichannel Raman system that is capable of measuring high signal-to-noise ratio, fluorescence-free Raman spectra of lung tissues within a measurement time of 1 second. Using this system, we collected a total of 210 Raman spectra from cancerous and non-cancerous lung tissues and analyzed these spectra by a least-squares fitting procedure for cancer diagnosis. RESULTS: The resultant sensitivity of cancer prediction was as high as 91%, with 97% specificity and an error margin of p<0.0001 according to Fisher's exact test. CONCLUSIONS: A method of diagnosing lung cancer efficiently and objectively using Raman spectroscopy has thus been established.     

Metallic stent placement in the pancreatic duct: an experimental study in the normal dog pancreas

PURPOSE: To evaluate radiologic and histologic changes in the pancreatic duct and parenchyma after placement of metallic stents in normal dog pancreatic ducts. MATERIALS AND METHODS: Eight dogs underwent duodenotomy and placement of a balloon-expandable metallic stent 1.5 mm in diameter and 1 cm in length in the main pancreatic duct. Two dogs each were killed at 1 day and 1, 3, and 5 months after stent placement. Pancreatic duct injection images were obtained before and immediately after stent placement and just before and after sacrifice. Macroscopic and microscopic examinations were also performed. RESULTS: Pancreatic duct injection images revealed mild dilation of pancreatic ducts related to the procedure immediately and 1 day after stent placement. Microscopically, denudation of the ductal epithelium and small foci of fat necrosis were observed. At 1 month or later, ductal stricture (n = 4) and occlusion (n = 2) were found at the downstream edge of the initially stent-implanted region associated with dilation of the duct upstream. Epithelial hyperplasia was observed at the sites of ductal stricture and occlusion at 1 and 3 months. Stents remained in the region in which they were initially placed until 1 month. However, stents had moved downstream from their initial positions at 3 and 5 months. One stent had migrated into the duodenum at 5 months. Stone formation was found in the ductal lumen and around the stents at 3 and 5 months. Ducts and parenchyma became fibrotic proportional to the period of stent implantation. CONCLUSION: Metallic stent placement in the pancreatic duct causes ductal and parenchymal damage related to the procedure and reaction to the stent in the normal dog pancreas.     

Disseminated infection due to Scedosporium apiospermum in a patient with acute myelogenous leukemia

A 62-year-old man diagnosed with acute myelogenous leukemia which had developed from myelodysplastic syndrome received cytarabine and idarubicine as an induction therapy. The patient developed pneumonia and bacterial sepsis during profound neutropenia. Fever and sepsis improved by using many anti-bacterials and anti-fungals but he became febrile again and complained of severe lumbar pain. 67Ga scintigram showed abnormal uptake in the lumbar vertebra and left sternoclavicular joint, suggesting a diagnosis of discitis and osteomyelitis in the lumbar vertebra and sternoclavicular arthritis. We biopsied the site several times but culture of the biopsy specimen could not isolate any pathogens, and high fever persisted for about 10 months despite administration of various anti-bacterials and anti-fungals. Finally we inserted a catheter into the abscess at the iliopsoas muscle and Scedosporium apiospermum was isolated in the bloody pus obtained from the catheter. Itraconazole and amphotericin B were restarted, and the high fever and lumbar pain improved rapidly. The findings of S. apiospermum infection in this patient emphasizes the importance of being aware of this pathogen in patients with hematologic malignancy during the neutropenic phase.     

Neopterin,biopterin, and nitric oxide concentrations in the cerebrospinal fluid of children with central nervous system infections

We measured neopterin, biopterin and nitric oxide (NO) concentrations in the cerebrospinal fluid of pediatric patients with central nervous system (CNS) infectious diseases. The nitric oxide and neopterin concentrations were significantly elevated in encephalitis patients, especially in two cases with serious neurological sequelae, while the biopterin levels were not elevated. The bacterial meningitis patients, on the contrary, had high cerebrospinal fluid concentrations of neopterin and biopterin, but not of NO. Although these findings are preliminary, it may suggest that cerebrospinal fluids nitric oxide would be a useful marker to prospect neurological prognoses in the CNS infections.     

Modulation by cyclic AMP and phorbol myristate acetate of cephaloridine-induced injury in rat renal cortical slices

Intracellular signaling pathways of cAMP and protein kinase C (PKC) have been suggested to modulate the generation of free radicals. We investigated the effects of cAMP and phorbol myristate acetate (PMA), a PKC activator, on cephaloridine (CER)-induced renal cell injury, which has been reported to be due to the generation of free radicals. Incubation of rat renal cortical slices with CER resulted in increases in lipid peroxidation and lactate dehydrogenase (LDH) release and in decreases in gluconeogenesis and p-aminohippurate (PAH) accumulation in rat renal cortical slices, suggesting free radical-induced injury in slices exposed to CER. A derivative of cAMP ameliorated not only the increase in lipid peroxidation but also the renal cell damage induced by CER. This amelioration by a cAMP derivative of lipid peroxidation and renal cell damage caused by CER was blocked by KT 5720, a protein kinase A (PKA) inhibitor. Lipid peroxidation and the indices of cell injury were increased by PMA. PMA also enhanced CER-induced lipid peroxidation and cell damage in the slices. This enhancement by PMA of CER-induced injury was blocked by H-7, a PKC inhibitor. These results indicated that intracellular signaling pathways of cAMP and PKC modulate free radical-mediated nephrotoxicity induced by CER.     

Protein binding of glufosinate and factors affecting it revealed by an equilibrium dialysis technique

We investigated the protein binding of glufosinate ammonium (GLF) and several factors affecting this binding using human serum albumin (HSA) and human volunteer serum under various conditions. The mean ratios of the free GLF (RFr-GLF) to 4% HSA were examined in the sera of patients described elsewhere at GLF levels from 1 microg/mL to 500 microg/mL; the range was found to be only from 0.80 to 0.88. Neither the incubation temperature nor buffers containing different chloride ion concentrations had any effect on the RFr-GLF to HSA. Moreover, the addition of heparin, glycoprotein-alpha1-acid (AAG), and sodium azide had no effect on the RFr-GLF. However, pH of the isotonic phosphate buffer and the addition of palmitic or oleic acid were seen to have an effect. In this study, the mean RFr-GLF to healthy human serum was 0.99. This high value was evidenced that GLF was rapidly excreted through the renal route.     

High-Output Heart Failure Caused by a Huge Renal Arteriovenous Fistula After Nephrectomy: Report of a Case

Postnephrectomy renal arteriovenous fistula (AVF) with an aneurysmal lesion is a rare clinical entity that may cause high-output heart failure. In this report, we describe the case of a 68-year-old man who had undergone nephrectomy for renal tuberculosis 43 years previously, in whom an acquired large renal AVF presenting as an aneurysm caused congestive cardiac failure. We also discuss the hemodynamic, hormonogenic (human arterial natriuretic polypeptide; hANP), and radiographic findings before and after surgery for the AVF. The AVF with an aneurysmal lesion was clearly visualized by three-dimensional-computerized tomographic (CT) scanning, and proximal ligation of the renal artery was followed by an uneventful recovery. This procedure can produce good results when a fistula is too large to allow safe embolization and when excision would be hazardous due to inflammation surrounding the fistula. Received: March 1, 2000 / Accepted: November 20, 2000