Al-type generalized amyloidosis showing a solitary duodenal tumor.

An amyloid tumor of the duodenum is a rare occurrence. A patient who presented with epigastric discomfort, in whom a barium meal study revealed a tumor of the duodenum is described. Upper gastrointestinal endoscopy showed a submucosal location of the tumor, and examination of a biopsy revealed amyloid deposition of the AL type. Diffuse tumor involvement of adjacent tissues of the duodenum and also deposits of amyloid fibrils in the liver and skin with no evidence of a chronic pre- existing disease in the patient led to the diagnosis of primary systemic amyloidosis. The distinguishing feature of this case was the formation of a solitary and relatively large tumor in the duodenum mimicking a submucosal tumor, which is in contrast to most reported cases of multiple and smaller amyloid tumors in other parts of the gastrointestinal tract.     

Evaluation of interleukin-12-induced interferon-y production in vitro by peripheral blood mononuclear cells in patients with chronic liver disease

BACKGROUND/AIMS: Interleukin-12 plays an important role in anti-tumor immune response by induction of interferon-gamma production by T cells and NK cells, and by activation of cytotoxic T cells and NK cells. We evaluated interleukin-12-induced interferon-gamma production as one of the immunological markers of patients with chronic liver diseases. METHODOLOGY: Interleukin-12-induced interferon-gamma production was measured in vitro in peripheral blood mononuclear cells from 28 hepatocellular carcinoma patients, 10 liver cirrhosis patients, 14 chronic hepatitis patients and 16 healthy individuals. RESULTS: The hepatocellular carcinoma patients exhibited a reduced interleukin-12 responsiveness for interferon-gamma production compared to the liver cirrhosis patients, the chronic hepatitis patients and the healthy individuals. The reduced interferon-gamma production seemed to roughly reflect clinical stage in the hepatocellular carcinoma patients. The interferon-gamma production correlated with neither alpha-fetoprotein nor protein induced by vitamin K absence II. CONCLUSIONS: The level of interleukin-12-induced interferon-gamma production by peripheral blood mononuclear cells in the patients with hepatocellular carcinoma was significantly lower than that in the patients with liver cirrhosis which is thought to be a premalignant state. The measurement of interferon-gamma production may be useful in evaluating severity of chronic liver disease from an immunological point of view.     

Concentrations of immunoreactive tonin in submandibular glands and saliva of the rat

The submandibular gland (SMG) of the rat contains tonin, an enzyme of serine proteases, which specifically cleaves angiotensinogen and angiotensin I to yield angiotensin II directly. Using a specific RIA for rat tonin, the present study was performed to examine the concentrations of immunoreactive (IR) tonin in SMG of normal Wistar male rats with various ages, those in SMG and saliva of normal adult males and females, and also its SMG levels of castrated males and testosterone-treated females. The concentrations of IR-tonin in SMG of immature 4 week old male rats were very low but rose exponentially with increasing age to reach adult levels (3-6 micrograms/mg wet tissue) in male rats after 6 week old or more. SMG of the adult male rat contained 10-fold more IR-tonin than that of the female rat and male saliva contained 5-fold more IR-tonin than that of females. The concentrations of SMG IR-tonin in the castrated males fell to about one-tenth the levels of normal males, whereas SMG IR-tonin levels in the testosterone-treated females increased about ten times more than those of normal females. These data confirm the sexual dimorphism of rat SMG with respect to the concentrations of tonin and indicate that androgens play an important role in regulating the synthesis and/or storage of tonin in rat SMG. It is also suggested that tonin is secreted into saliva in concentrations reflecting its SMG levels. However, biological significance of tonin in SMG and saliva remains obscure.     

Effects of laser irradiation on human erythrocytes: Considerations concerning clinical laser angioplasty

Recent studies demonstrate the potential use of laser to vaporize human coronary atherosclerotic plaques. The laser energy is transmitted through flexible quartz fiber and discharged intravascularly. Since red blood cells could be exposed to intense heat, we examined effects of laser irradiation on human erythrocytes. Blood was obtained and placed in 5 ethylene diaminetetracidic acid (EDTA) vials for each normal donor. A flexible 400 diameter core quartz fiber coupled to an argon-ion laser source was positioned 1 cm above the surface of 1.5 ml blood. Four vials were exposed to 5 W laser beam for 5, 10, 15, or 20 s; the remaining vial was left untreated. Packed cell volume fell primarily during the first 5 s of laser exposure (p<0.01) and plateaued beyond 5 s. Plasma hemoglobin (Hgb) rose progressively with each increased duration of exposure (p<0.01). This study indicates that lysis of erythrocytes occurs in cells exposed directly to the laser beam. However, beyond the direct beam, damage to red cell membrane took place as evident by progressive Hgb leakage into plasma despite no further cell lysis. These observations require consideration during clinical laser angioplasty.     

Interleukin 6 expression in coronary circulation after coronary angioplasty as a risk factor for restenosis

OBJECTIVE—To investigate changes in cytokine expression in the coronary circulation induced by percutaneous transluminal coronary angioplasty (PTCA).
METHODS—The study involved 32 patients with ischaemic heart disease who underwent elective PTCA for isolated stenotic lesions of the left coronary artery. Ten patients had plain old balloon angioplasty, 10 had percutaneous transluminal rotational atherectomy, and 12 had stent implantation. Blood samples were drawn from the coronary sinus before and immediately after PTCA. Plasma concentrations of interleukin 6 (IL-6), platelet derived growth factor (PDGF), monocyte chemoattractant protein 1 (MCP-1), and macrophage coronary stimulating factor (M-CSF) were measured. The patients were scheduled for follow up angiography six months after PTCA. Late loss index was calculated using quantitative coronary angiography.
RESULTS—IL-6 concentrations in coronary sinus blood increased immediately after PTCA (p < 0.001), but there was no change in PDGF, MCP-1, or M-CSF. There was a positive correlation between changes in IL-6 concentrations immediately after PTCA and late loss index six months after PTCA (r = 0.73, p < 0.001). IL-6 concentrations in coronary sinus blood were higher in patients with late restenosis than in those without restenosis (p < 0.001).
CONCLUSIONS—PTCA induces IL-6 production in the coronary circulation. This may induce subsequent inflammatory responses in injured vessels and play an important role in late restenosis after PTCA.


Keywords: inflammation; cytokine; restenosis     

Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival

Background  

The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases.     

Application of real-time RT-PCR to quantifying gene expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human abdominal aortic aneurysm

BACKGROUND: The relative expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), key regulators in remodeling of extracellular matrix, are considered to play a pivotal role in the development of abdominal aortic aneurysm (AAA). However, few data exist regarding quantitative assessment of their expression in clinical settings. METHODS: In 22 patients with AAA who underwent graft replacement, tissue samples of the AAA and non-dilated aorta were obtained. Using a real-time RT-PCR method that enabled quantitative measurement of mRNA levels in small tissue samples, we determined gene expression levels of MMPs and TIMPs relative to that of glutaraldehyde 3-phosphate dehydrogenase in each sample. RESULTS: The expression levels of the MMP-1 and -3 genes were significantly augmented in AAA compared with non-dilated regions (4.48 +/- 2.01 versus 0.26 +/- 0.12, P < 0.01 and 1.89 +/- 1.00 versus 5.01 +/- 0.97, P < 0.05, respectively). Although genes for TIMP-1, -2 and -3 tended to be upregulated in AAA, relative expression levels of MMP-1 to TIMP-1, MMP-1 to TIMP-2, MMP-1 to TIMP-3, and MMP-3 to TIMP-2 were still higher in AAA than in non-dilated regions (1.12 +/- 0.63 versus 0.10 +/- 0.03, 4.13 +/- 1.12 versus 0.43 +/- 0.11, 1.61 +/- 0.59 versus 0.14 +/- 0.03, and 7.81 +/- 1.60 versus 2.56 +/- 0.76, respectively, P < 0.05). CONCLUSION: These results demonstrate that the present real-time RT-PCR method is reliable for the determination of mRNA levels in small samples of vascular tissue and that disproportional expression of both MMP-1 and MMP-3 relative to TIMPs relates pathologically to the evolution of AAA.     

Illegitimate recombination mediated in vitro by DNA gyrase of Escherichia coli: structure of recombinant DNA molecules.

We have developed a cell-free system from Escherichia coli for studying illegitimate recombination between nonhomologous DNA molecules. The recombination is stimulated by oxolinic acid, an inhibitor of DNA gyrase. The stimulation is abolished by coumermycin A1 and is not found in extracts of nalidixic acid-resistant (gyrA) mutants. We therefore inferred that DNA gyrase directly participates in illegitimate recombination, at least in the presence of oxolinic acid [Ikeda, H., Moriya, K. & Matsumoto, T. (1981) Cold Spring Harbor Symp. Quant. Biol. 45, 399--408]. The structure of recombinant DNA molecules formed in the presence of oxolinic acid from a cross between phage lambda and plasmid pBR322 DNAs was analyzed by heteroduplex mapping. Among nine isolates tested, two recombinants were formed by the insertion of the plasmid into the lambda genome. The seven other recombinants had more complicated genome structures. Insertion of pBR322 was accompanied by a deletion on one of the genomes. In all cases, the end points of deletions coincided with one end of the pBR322 insertion. Recombination sites seemed to be distributed randomly on the lambda and pBR322 genomes. Analysis of nucleotide sequences of the recombination junctions proved that the crossover took place between nonhomologous DNA sequences. A model for DNA gyrase-mediated illegitimate recombination is discussed.     

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in Nagano, Japan: clinical, radiological, and cytokine studies of 13 patients

OBJECTIVE: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) has so far been reported almost exclusively from the USA and Europe. We carried out this study to define the clinical characteristics of this syndrome in Japanese patients. METHODS: Prospectively, we identified 13 Japanese patients with RS3PE (5 men and 8 women, age 72.7 +/- 11.8 years (mean +/- SD)) without underlying neoplasm. Their clinical features were summarized, pertinent laboratory data including serum/synovial interleukin-6 (IL-6) concentrations were obtained, and extensive radiologic studies using magnetic resonance imaging and 67gallium-citrate (67Ga) whole body scintigram were performed. RESULTS: All patients suffered from proximal arthralgia/myalgia in addition to typical distal symptoms of RS3PE, and all experienced systemic symptoms such as fever, malaise, and weight loss. In laboratory examinations, anemia and elevated inflammatory markers were often remarkable. Magnetic resonance imaging showed severe tenosynovitis of the hands. 67Ga-scintigram revealed radioisotope accumulation in both proximal and distal joints of the extremities. IL-6 activity was markedly elevated both in the serum (mean 82.4 +/- 62.1 (SD) pg/ml, normal range 0.157-2.94) and in the synovial fluid (mean 3350 +/- 633 (SD) pg/ml). CONCLUSION: Compared with cases reported previously from the USA/Europe, Japanese patients with RS3PE are characterized by more prominent systemic symptoms/signs associated with marked inflammatory responses including elevated IL-6 activity. All patients had proximal as well as distal synovitis which could be demonstrated by 67Ga-scintigram. These clinical features were very similar to those of polymyalgia rheumatica, suggesting that RS3PE and polymyalgia rheumatica are closely related disorders which may have a common pathogenesis.