Reversal of ischemia-induced mitochondrial dysfunction after coronary reperfusion

This study was designed to clarify the mechanism of the reversal of ischemia-induced mitochondrial dysfunction after a reperfusion of the myocardium in dogs. The occlusion of the left anterior descending coronary artery for 30 min led to the significant increase of acyl-CoA level in ischemic mitochondria and the ischemic mitochondrial function was disturbed. Pre-infusion of 1 ml/kg of lipid before occlusion further increased the acyl-CoA accumulation in ischemic mitochondria, and concomitantly, the mitochondrial dysfunction was extended much more. On the other hand, 40 min of reperfusion following 30 min of occlusion diminished the accumulation of acyl-CoA in the reperfused mitochondria and restored the mitochondrial function. However, when lipid was pre-infused, acyl-CoA level in the reperfused mitochondria was still high and mitochondrial dysfunction was observed. Administration of carnitine prior to reperfusion not only suppressed the accumulation of acyl-CoA in the reperfused mitochondria but also preserved the mitochondrial function, despite the pre-infusion of lipid. There was a clear reciprocal correlation (r = ?0.97) between acyl-CoA level and mitochondrial function. These results suggest that acyl-CoA accumulation is one of the important factors in ischemia-induced mitochondrial dysfunction, and that reversal of the dysfunction after reperfusion is closely dependent upon the lowering of the acyl-CoA accumulation.     

Evaluation of Streptococcus pneumoniae-urinary antigen detection kit in patients with community acquired pneumonia

We evaluated a new rapid urinary antigen detection kit. NOW Streptococcus pneumoniae (Binax Inc., USA) that detected S. pneumoniae antigen by immunochromatographic membrane assay, with 66 Japanese adult patients of community acquired pneumonia. Twenty-two (33.3%) patients were found to be positive with the kit and S. pneumoniae was isolated from six patients (27.3%) of these 22 patients. S. pneumoniae was not isolated from eight of the 22 patients by blood or sputum culture. Analysis of clinical laboratory data showed that the levels of C-reactive protein (CRP) in the serum were significantly higher in the urine-antigen positive group than those in the urine-antigen negative group. There were no significant difference between the two groups including renal function, urinalysis, clinical symptom, and severity of pneumonia. Our study suggests that more cases of community acquired pneumonia are caused by S. pneumoniae than conventional tests can currently confirm. Since it is not technically complex, does not require equipment, and detects within as quickly as in 15 minutes, the S. pneumoniae urinary antigen kit is useful for rapid diagnosis of community acquired pneumonia in adults.     

Carotid intima-media thickness is increased in subjects with ischemic heart disease having a familial incidence

OBJECTIVES: A family history of ischemic heart disease (IHD) is an independent risk factor for cardiovascular events. However, the mechanisms underlying this susceptibility have not been fully elucidated. The authors hypothesized that an important mediator of the familial incidence of IHD is subclinical atherosclerosis, which is detectable by noninvasive imaging. METHODS: One hundred forty-seven consecutive subjects (mean age 61.9 years, 57% men) were studied for one year using carotid ultra-sonogrophy for general medical screening, and familial IHD events were validated. Using a 7.5 MHz linear array transducer, carotid intima-media thickness (IMT) and carotid plaque were assessed. Subjects were subsequently divided into four groups based on the severity of IMT. RESULTS: The familial incidence of IHD and incidence of plaque were associated with the severity of IMT. No significant differences in risk factors were found between subjects with and without a family history of IHD. CONCLUSIONS: These findings suggest that subclinical atherosclerosis, as assessed in the carotid arteries, is more prevalent in individuals with a family history of IHD.     

Bikunin suppresses lipopolysaccharide-induced lethality through down-regulation of tumor necrosis factor- alpha and interleukin-1 beta in macrophages

BACKGROUND: Lipopolysaccharide (LPS) is the primary mediator of gram-negative sepsis; it induces the production of macrophage-derived cytokines. It has been shown that bikunin, a Kunitz-type protease inhibitor, inhibits LPS-induced cytokine expression. METHODS: To explore the role of bikunin, bikunin knockout (Bik(-/-)) mice were used for in vitro cytokine experiments and in vivo animal models. RESULTS: We show that a higher level of LPS-mediated death was induced in Bik(-/-), compared with wild-type (wt), mice; the administration of bikunin caused a significant reduction in LPS-induced lethality; LPS significantly increased tumor necrosis factor (TNF)- alpha and interleukin-1 beta levels in Bik(-/-), relative to wt, mice after LPS challenge; concomitant administration of bikunin inhibited the LPS-induced plasma levels of these cytokines; bikunin suppressed the LPS-induced up-regulation of cytokine expression through the suppression of the phosphorylation of ERK1/2, JNK, and p38 in macrophages; and LPS-induced up-regulation of TNF- alpha expression was not enhanced in Bik(-/-) macrophages without endogenous bikunin. CONCLUSIONS: These data allow us to speculate that the increased sensitivity of Bik(-/-) mice to LPS-induced death in vivo is due to a lack of circulating bikunin in plasma. Bikunin may play a role as a potent anti-inflammatory agent.     

Gastrointestinal stromal tumors with exon 8 c-kit gene mutation might occur at extragastric sites and have metastasis-prone nature

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the human gut. Most sporadic GISTs have somatic gain-of-function mutations of the c-kit gene. The mutations are frequently found at exon 11, sometimes at exon 9 and rarely at exon 13 or 17. Recently, exon 8 c-kit gene mutations were reported in very minor proportion of sporadic GISTs. We also found 3 GISTs with exon 8 c-kit gene mutations in approximately 1,000 sporadic GISTs examined. In the present report, we showed the clinicopathological data of those GISTs. One case had a deletion of codon 419 of aspartate, and 2 cases had a substitution of 3 amino acids of codon 417 to codon 419 to tyrosine. The former was the same mutation recently reported in 2 GIST cases, but the latter has not been reported in any GISTs. All three cases occurred at extragastric sites and two of three showed distant metastasis. Since the remaining case was regarded as high risk for recurrence, imatinib adjuvant treatment has been done without evidence of metastasis. Our results confirmed the idea that exon 8 mutations are minor but actually existing abnormalities in sporadic GISTs, and suggested that such GISTs have a feature of extragastric development and a metastasis-prone nature. Since the exon 8 mutations appeared to be really sensitive to imatinib as shown in the present case study, accurate genotyping including exon 8 of the c-kit gene is necessary in GISTs to predict response to imatinib in both the unresectable/metastatic and adjuvant settings.     

Thoracoscopic rib resection and reconstruction of chest wall: Our clinical experience

Chest wall resection is traditionally performed via open thoracotomy, a procedure that increases surgical morbidity and reduces postoperative quality of life. Conversely, thoracoscopic chest wall resection may minimize invasiveness but the optimal procedure remains uncertain. We previously reported rib resection using a pneumatic high‐speed power drill during video‐assisted thoracoscopic surgery for selected lung cancer patients. In this report, we present two cases of chest wall tumor resected using the drill via the thoracoscopic approach. We also report thoracoscopic chest wall reconstruction in one patient using a patch sheet.     

Clinical manifestations in patients with hereditary nonpolyposis colorectal cancer

The clinical manifestations of 1,042 Japanese patients with nonpolyposis colorectal cancer who underwent a resection between 1972 and 1992 at the National Kyushu Cancer Center were examined. Hereditary nonpolyposis colorectal cancer (HNPCC) was found in 39 (3.7%) patients. Some characteristic findings in HNPCC cases included early age of onset, a preponderance of right colon cancers, an increased frequency of colorectal cancers, and a favorable survival. Metachronous (postoperative) colorectal cancers developed significantly more often in cases with HNPCC than in those without (12.8% vs. 1.8%, P = 0.0001). Metachronous (postoperative) extracolonic cancers tended to develop more often in cases with HNPCC than in those without (10.2% vs. 3.5%, P = 0.053). In cases with HNPCC, the mean interval between the initial surgery and the diagnosis of the second cancer was 61 months (range; 12–153 months). These findings thus indicate the importance of routine and long-term follow-up to identify any second lesions, especially in patients with HNPCC. © 1996 Wiley-Liss, Inc.     

Establishment and characterization of two cultured cell lines derived from malignant rhabdoid tumors of the kidney

Malignant rhabdoid tumor of the kidney (RTK) is a rare renal sarcoma of childhood. Its histogenesis is unclear, and it is highly resistant to multimodality therapy. To elucidate the origin and the oncogenetic potential of RTK, we investigated the characteristics of 2 newly established RTK cell lines, SWT-1 and SWT-2. Both cell lines were verified to be RTK, since they did not exhibit contact inhibition and exhibited intermediate filaments, a specific marker for RTK. These cells possess the characteristics of mesenchymal cells based on their positive reactions with anti-vimentin and anti-laminin antibodies and their negative reactions with anti-keratin and anti-desmin antibodies. The karyotype of SWT-1 was 46,XX and that of SWT-2 was 46,XX,del(II)(pter-p13::p12-qter). Since 11p13 is the location of the WT-1 tumor-suppressor gene, and del(11p13) is associated with the aniridia-Wilms'-tumor syndrome, these findings link RTK with Wilms' tumor. While SWT-1 was negative for the tumor markers examined, SWT-2 released tissue polypeptide antigen into the culture supernatant. No rearrangement or amplification of the myc and ras oncogenes or of the p53 tumor-suppressor gene were detected. Wild-type RB protein and cyclin A were expressed in both cells. Our data suggest that these 2 cell lines may be useful in identifying the oncogenetic pattern of RTK. © 1996 Wiley-Liss, Inc.