iNOS-dependent DNA damage in patients with malignant fibrous histiocytoma in relation to prognosis

Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas. MFH has been proposed to be a lesion accompanied with inflammatory responses. During chronic inflammation, reactive nitrogen and oxygen species generated from inflammatory cells are considered to participate in carcinogenesis by causing DNA damage. 8-nitroguanine is a mutagenic nitrative DNA lesion formed during chronic inflammation. We examined whether nitrative DNA damage is related to the prognosis of MFH patients. We performed immunohistochemical analyses to examine the distribution of DNA damage and the expression of inflammation-related molecules including inducible nitric oxide synthase (iNOS), nuclear factor-kappaB (NF-kappaB), and cyclooxygenase-2 (COX-2) in clinical specimens from 25 patients with MFH. We also analyzed the correlation of DNA damage or the expression of these genes with the prognosis of MFH patients. Immunohistochemical staining revealed that the formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidative DNA lesion, occurred to a much greater extent in MFH tissue specimens from deceased patients than in live patients. iNOS, NF-kappaB and COX-2 were colocalized with 8-nitroguanine in MFH tissues. It is noteworthy that the statistical analysis using the Kaplan-Meier method demonstrated strong 8-nitroguanine staining to be associated with a poor prognosis. In conclusion, 8-nitroguanine appears to participate in not only the initiation and promotion of MFH, but also in the progression of MFH, and could therefore be used as a promising biomarker to evaluate the prognosis of cancer patients.     

Progression of gastric cancer observed for three and a half years under S-1 administration

A 60-year-old male patient noticed a sudden epigastric pain and visited our hospital for treatment. Active gastric ulcer was discovered by a routine gastrointestinal endoscopy. Moderately differenciated tubular adenocarcinoma was confirmed by biopsy and was advised to take surgical treatment. However, he refused to go on with gastrectomy and selected to take S-1 as an oral anti-tumor drug instead. Despite many approaches to convince the patient to have surgery, three and a half years passed. Macroscopic findings have changed from 0-IIc type to infiltrating advanced type cancer. Finally, we persuaded him to take a surgical resection, but peritoneal dissemination was evident. Using S-1 against gastric cancer is common. However, S-1 should not be used before another evidence-based curative treatment is available. Furthermore, drugs should have been changed to others, if not effective. A rare clinical course is discussed.     

Two cases of colon cancer after resection of recurrence at peritoneal dissemination were for long-term survival with adjuvant chemotherapy

Generally the peritoneal dissemination of digestive cancer was difficult to control. The symptom of dissemination will decrease quality of life (QOL) for these patients. The diagnosis for the range of dissemination was difficult. Therefore, the decision of the treatment was wavered between an operation and chemotherapy. The effect of chemotherapy was controversial so the cure was inconsistent. We experienced with two recurrent colon cancer patients who underwent resection of peritoneal dissemination and adjuvant chemotherapy. Case 1 was a 62-year-old man. He was operated for left colectomy against descending colon cancer with perforation. After two years, the recurrence of peritoneal dissemination and short bowel obstruction appeared. He was performed short bowel resection and FOLFIRI chemotherapy after surgery. Case 2 was a 72-year-old woman. She was operated on sigmidectomy against sigmoid colon cancer. After three years, the recurrence of peritoneal dissemination at the anastomotic lesion appeared. She was performed low anterior resection (LAR) and S-1 chemotherapy after surgery. But after 3.5 years, the peritoneal dissemination at the anastomotic lesion appeared once more. We decided to have LAR operation and FOLFOX 4 chemotherapy. Both cases maintained a good QOL for a long time. The operation against peritoneal dissemination was one of the good treatments if the range of peritoneal dissemination was clearly restricted.     

Modulation of melanocyte-stimulating hormone receptor expression on normal human melanocytes: evidence for a regulatory role of ultraviolet B, interleukin-1α, interleukin-1β, endothelin-1 and tumour necrosis factor-α

Melanocyte-stimulating hormone (MSH) receptor binding activity and melanocortin-1 receptor (MC1-R) gene expression on normal human melanocytes have been studied as responses to the effects of ultraviolet B (UVB), interleukin-1 (IL-1), endothelin-1 (ET-1) and tumour necrosis factor-α (TNF-α), which are known as UV sensitive regulators of melanocytic function. MSH receptor (MSH-R) binding activity was upregulated by UVB, IL-1α, -1β and ET-1, but was downregulated by TNF-α. Northern blot analysis showed that MC1-R mRNA expression was induced 24 h after UVB irradiation in a dose-dependent manner, and that 24-h treatment with ET-1 also induced an expression of MC1-R mRNA, whereas TNF-α downregulated the expression. In addition, IL-1α and -1β have a small but real inductive effect on MC1-R mRNA expression. Taken together, our results suggest a model in which higher MC1-R mRNA expression is accompanied by upregulation of MSH-R binding activity, and enhanced by UVB or cytokines sensitive to UVB. Such a regulatory system would enable normal human melanocytes to respond to MSH more efficiently and induce an increase of melanization of the skin through the MSH/MSH-R system after UVB radiation.     

15The effect of Lower Esophageal Sphincter (LES) electrical stimulation on LES pressure

Background: Electrical stimulation (ES) of the stomach has been shown to modulate LESP. Electrical stimulation, using neural high frequency stimulation (NGES) can induce contractions of the smooth muscle of the gut. The purpose of this study was to determine if electrical stimulation of the LES can affect LESP. Methods: Four female hound dogs, weight: 20–25 kg, underwent an esophagostomy that allowed the introduction of a sleeve manometry catheter into the esophagus. They were also implanted with a pair of electrodes along the longitudinal axis of the LES. After 3 weeks of recovery, they underwent esophageal manometry recording during control and ES, performed randomly on separate days, using 4 different stimulations: 1‐Low frequency: freq: 6 cycles/min, pulse: 350 milisec, amp: 5 mAmp; 2 High‐frequency: freq: 50 Hz, pulse: 1 milisec, amp: 5 mAmp; 3‐ NGES: freq: 50 Hz, pulse:20 milisec, amp:10 volts; 4‐ High‐frequency, circular: freq: 20 Hz, pulse:1 milisec, amp:5 mAmp. All recordings were performed 1 hour after consumption of 3 ounces of canned dog food, to prevent fluctuations in LESP and under mild sedation (acepromazine 0.5 mg kg^­1). Tests consisted, during ES days, of 3 periods of 20 minutes each: control , stimulation and post stimulation. The effect of NGES was also tested under anesthesia and following administration of L‐NAME 50 mg kg^­1 IV. and also atropine 0.05 mg kg^­1 IV. Analysis: area under the curve (AUC) and pressure were compared among the 3 periods. Data shown as mean ± SD, ANOVA and t‐test, p < 0.05. Results: Sustained increase in LESP was observed during low frequency stimulation, 32.1 ± 12.8 vs. 42.4 ± 18.0 vs. 50.1 ± 23.6, control vs. stimulation vs. post stimulation respectively, p = 0.013. AUC also significantly increased during and after stimulation, 39,320.3 ± 15,722 vs. 51,294 ± 21,826 vs. 59,823.6 ± 28,198.4 mmHgxsec, control vs. stimulation vs. post stimulation respectively, p = 0.01. There was no significant change with other types of ES. NGES induced an initial rise in LESP followed within few seconds by relaxation with slow resumption of pressure over a 1 minute period. L‐NAME increased LESP and augmented the initial rise in LESP following NGES but markedly diminished or abolished the relaxation phase. Atropine lowered LESP and abolished the initial rise in LESP induced by NGES. Conclusions: Low frequency ES of the LES increases LESP in conscious dogs. NGES has dual effect on LESP: an initial stimulation, cholinergically mediated, followed by relaxation mediated by nitric oxide.     

Parkinson's disease mortality among male anesthesiologists and internists.

Clusters of Parkinson's disease (PD) among healthcare professionals have been interpreted as evidence of an infectious etiology. Anesthetic gases have also been associated with parkinsonism symptoms and PD among patients undergoing general anesthesia. We investigated PD mortality among large cohorts of male U.S. anesthesiologists (n = 33,040) and internal medicine physicians (n = 33,044). PD mortality for any mention on a death certificate was lower than rates in U.S. men during 1979-1995 for both groups, although anesthesiologists had a significantly elevated risk for PD as underlying cause of death for 10-year follow-up. Direct comparisons of mortality between the two cohorts indicated excess PD mortality in anesthesiologists for >10-year follow-up for any mention and for underlying cause of death. These findings lend some support to the hypothesis that infectious agents or anesthetic gases may be associated etiologically with PD.     

Enteritis necroticans 'pigbel' in a Japanese diabetic adult

Enteritis necroticans 'pigbel' is caused by Clostridium perfringens type C but has rarely been reported in developed countries. A 50-year-old Japanese man with untreated diabetes mellitus (DM) presented with diarrhea and abdominal pain. Intraoperative endoscopic and macroscopic examination disclosed segmental annular mucosal lesions characteristic of clostridial enteritis. Clostridial infection type C was verified on pathological, and immunohistochemical analysis. Although rare, the disease is likely to be underdiagnosed. Hence, the pathology and immunohistochemistry of segmental enteritis with annular mucosal lesions should be examined to establish a diagnosis of enteritis necroticans even in mildly affected patients, and especially those with DM.     

Refractoriness to platelet transfusion following partial hepatectomy for hepatocellular carcinoma: report of two cases

Refractoriness to platelet transfusion indicates a condition in which an expected increase in platelet count is not attained after platelet transfusion. We report herein two cases of refractoriness to platelet transfusion that were caused by the presence of antibodies against the human leukocyte antigen following partial hepatectomy for hepatocellular carcinoma. Due to low postoperative platelet counts in the first case, the patient was transfused with 75 units of platelet concentrate for 3 days after surgery, but was unable to gain a significant increase in the platelet count because of platelet transfusion refractoriness due to anti-human leukocyte antigen antibodies. This case was not complicated and had a favorable clinical course. Despite being transfused with 60 units of platelet concentrate during the 2 days after surgery, the patient's platelet count in the second case did not increase because of the presence of anti-human leukocyte antigen antibodies. Bleeding from the cut surface of the liver into the intraperitoneal cavity was found on the second postoperative day because of a decrease in platelet count. On postoperative day 5, disseminated intravascular coagulation occurred. Perioperative refractoriness to platelet transfusion is an intractable complication since no efficient treatment is available. Preoperative examinations for anti-platelet antibodies should be performed in patients undergoing hepatectomy for hepatocellular carcinoma. This is especially true in cases of decreased platelet counts due to preceding liver cirrhosis and when the prediction for postoperative platelet transfusions is necessary.     

Left ventricular free wall rupture after reperfusion therapy for acute myocardial infarction

We evaluated the clinical significance of angiographic indexes and pericardial involvement in predicting increased risk of free wall rupture after reperfusion therapy and found that Thrombolysis In Myocardial Infarction (TIMI) <3 flow grade after reperfusion therapy was a significant variable related to the free wall rupture. Moreover, pericardial rub was found to be a significant variable related to TIMI <3 grade flow after reperfusion, which indicates that detection of pericardial rub is one of the clinical signs that predicts inadequate anterograde flow of the infarct-related artery after reperfusion and hence, higher risk for free wall rupture.