[Expandable metallic stent treatment for obstructive colorectal cancer patients].

UNLABELLED: The expandable metallic stent (EMS) have been used to treat obstructive colorectal cancer. We used EMS in 13 out of 14 cases of obstructive colorectal carcinoma patients (insertion rate 93%). Of these 13 cases, 6 cases were male patients, and 7 cases were female patients. The average age was 69.1-years-old (44-87). The placement of insertion part in rectum and sigmoid colon was 8 cases and 5 cases, respectively. We detained Ultraflex non-covered type for all patients. Seven patients were able to have an operation after stenting. After the stent treatment, 11 patients were able to eat, and 7 patients were discharged from hospital. COMPLICATIONS: perforation and stent migration were occurred in one case. These results suggested that EMS might be an effective treatment for obstructive colorectal carcinoma.

[Pancreatic metastasis of malignant melanoma diagnosed by EUS-guided fine needle aspiration (EUS-FNA)].

Pancreatic metastasis of malignant melanoma is rarely diagnosed while the patient is alive. We report a case of metastatic melanoma of the pancreas in a 35-year-old woman presenting with a solid mass of the pancreas. Her past medical history included a radical hysterectomy 2 years previously for malignant melanoma of the vagina. Twelve months later, lung metastasis was also resected. EUS-guided fine needle aspiration (EUS-FNA) identified that the pancreatic tumor was histologically and immunohistochemically identical to the surgical specimen of her lung neoplasm. Imaging studies including US, CT, and MRI have limited value to distinguish the tumors from primary ductal adenocarcinoma. EUS-FNA can provide tissue diagnosis from pancreatic masses, specifically when other modalities have failed.

Escherichia coli Hmp, an "oxygen-binding flavohaemoprotein", produces superoxide anion and self-destructs.

Escherichia coli Hmp is a homologue of Ralstonia eutropha FHP, the first reported bacterial flavohaemoglobin, and functions in NO detoxification. Photolysis of CO-ligated Hmp in the presence of oxygen gave a photodissociable oxy species with k(on) 2.82x10(7) M(-1) s(-1) and k(off) 4.49x10(3) s(-1). The dissociation constant of the primary O(2) compound was 160 microM (25 degrees C, pH 7.0). In order to detect superoxide formation, ferric horseradish peroxidase was used. Hmp formed the oxy compound within milliseconds, followed by formation of compound III, arising from superoxide formation. The rate of superoxide formation was independent of oxygen concentration between 0.05 and 0.7 mM oxygen, suggesting a K(m) <0.05 mM. During prolonged oxidation of NADH, the spectral signals of Hmp decayed and iron was released in a process prevented by superoxide dismutase or catalase. NADH oxidation by purified Hmp was characterised by progressive slowing of oxygen uptake. Inclusion of NO, superoxide dismutase or catalase during NADH oxidation partially protected oxygen uptake, consistent with the formation, in the absence of NO, of reactive oxygen species that inhibit Hmp function. The results are discussed in relation to the tight control exerted on Hmp synthesis in vivo.

Natural history of colorectal nonpolypoid adenomas: a prospective colonoscopic study and relation with cell kinetics and K-ras mutations.

OBJECTIVE: Serial colonoscopic observations were prospectively conducted to elucidate the natural history of nonpolypoid tumors. Furthermore, to clarify whether cell kinetic status affects the tumor development, proliferative indices, apoptotic indices, and K-ras codon 12 point mutations on biopsy specimens were investigated. METHODS: Seventy-five colorectal tumors, 13 polypoid and 62 nonpolypoid type (56 flat elevated and six depressed type) were studied. Proliferating and apoptotic cells were detected with anti-Ki-67 antibody and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method, respectively. Point mutations at K-ras codon 12 were examined by enriched polymerase chain reaction-based restriction fragment length polymorphism assay. RESULTS: The average follow-up period was 22 months (range 1-50). The lesions of subsequent exophytic growth, unchanged shape, depressed growth, and disappearance were observed in 0%, 92%, 0%, and 8% of polypoid type, in 39%, 39%, 13%, and 9% of flat elevated type, and in 33%, 67%, 0%, and 0% of depressed type, respectively. There was no significant difference in tumor size between initial and follow-up colonoscopy. Nonpolypoid tumors apparently changed to the exophytic growth during 2 yr or more. The tumors with exophytic growth had significantly higher proliferative indices/apoptotic indices ratios than those with unchanged morphology and disappearance/depressed growth (p < 0.05, respectively). K-ras codon 12 point mutations did not correlate with tumor development. CONCLUSIONS: Cell kinetic status plays an important role in determining minute colorectal tumor development, but not K-ras codon 12 mutations. Minute nonpolypoid adenomas frequently tend to grow slowly, and nearly 40% of those become the exophytic growth with time. Most of minute nonpolypoid tumors seem to follow the adenoma-carcinoma sequence.

Escherichia coli flavohaemoglobin (Hmp) reduces cytochrome c and Fe(III)-hydroxamate K by electron transfer from NADH via FAD: sensitivity of oxidoreductase activity to haem-bound dioxygen.

Escherichia coli flavohaemoglobin (Hmp) reduced purified mitochondrial cytochrome c aerobically in a reaction that was not substantially inhibited by superoxide dismutase, demonstrating that superoxide anion, the product of O2 reduction by Hmp, did not contribute markedly to cytochrome c reduction. Cytochrome c was reduced by Hmp even in the presence of 0.5 mM CO, when the haem B was locked in the ferrous, low-spin state, demonstrating that electron transfer to cytochrome c from NADH was via FAD, not haem. Hmp also reduced the ferrisiderophore complex Fe(III)-hydroxamate K from Rhizobium leguminosarum bv. viciae anaerobically in a CO-insensitive manner, but at low rates and with low affinity for this substrate. The NADH-cytochrome c oxidoreductase activity of Hmp was slightly sensitive to the binding and reduction of O2 at the haem. The Vmax of cytochrome c reduction fell from 7.1 s-1 in the presence of 0.5 mM CO to 5.0 s-1 in the presence of 100 microM O2, with no significant change in K(m) for cytochrome c (6.8 to 7.3 microM, respectively). O2 at near-micromolar concentrations diminished cytochrome c reduction to a similar extent as did 100 microM O2. Thus, Hmp acts as a reductase of broad specificity, apparently without involvement of electron transfer via the globin-like haem. These data are consistent with the hypothesis that Hmp could act as an intracellular sensor of O2 since, in the absence of O2, electron flux from FAD to other electron acceptors increases. However, the nature of such acceptors in vivo is not known and alternative models for O2 sensing are also considered.

Reactions of the Escherichia coli flavohaemoglobin (Hmp) with NADH and near-micromolar oxygen: oxygen affinity of NADH oxidase activity.

The soluble flavohaemoglobin (Hmp) of Escherichia coli, product of the hmp gene, contains haem B and FAD in a single polypeptide of molecular mass 44 kDa. The function of this protein (and of the similar proteins identified in several bacteria and yeast) is unknown, but the observation that the binding of oxygen to haem modulates the reduction level of FAD has suggested that Hmp could act as an oxygen sensor. Here, stopped-flow, rapid-scan spectroscopy has shown that the oxidized protein reacts rapidly with NADH to form an oxygenated species, even when efforts are made to reduce oxygen concentrations to sub-micromolar levels, suggesting a high affinity for this ligand. As is the case at high oxygen concentrations (130 microM), oxygenated species formation was kinetically and spectrally heterogeneous. Between 12 ms and 1 s after mixing, following transient formation of the deoxy form and its reaction with dioxygen, a steady-state level of the oxygenated species was attained. During the oxygenated steady state, the flavin remained largely oxidized, as observed previously at 130 microM oxygen. Hmp is an NADH oxidase; on exhaustion of oxygen by reduction (in < 10 s under these conditions), the oxygenated species disappeared to generate the deoxy Fe(II) haem, whereupon the flavin was reduced. The affinity for oxygen during NADH oxidation was measured by continuous dual-wavelength monitoring of the deoxygenation of oxymyoglobin. The Km for oxygen was 2.6 microM, much higher than the Km values determined, using the same method, for the membrane-bound terminal oxidases cytochromes bo' and bd. These results show that the oxidase activity of Hmp, but not necessarily oxygen binding, would be minimal at oxygen concentrations that limit terminal oxidase function.