Human group IIA secretory phospholipase A2 induces neuronal cell death via apoptosis.

Expression of group IIA secretory phospholipase A2 (sPLA2-IIA) is documented in the cerebral cortex (CTX) after ischemia, suggesting that sPLA2-IIA is associated with neurodegeneration. However, how sPLA2-IIA is involved in the neurodegeneration remains obscure. To clarify the pathologic role of sPLA2-IIA, we examined its neurotoxicity in rats that had the middle cerebral artery occluded and in primary cultures of cortical neurons. After occlusion, sPLA2 activity was increased in the CTX. An sPLA2 inhibitor, indoxam, significantly ameliorated not only the elevated activity of the sPLA2 but also the neurodegeneration in the CTX. The neuroprotective effect of indoxam was observed even when it was administered after occlusion. In primary cultures, sPLA2-IIA caused marked neuronal cell death. Morphologic and ultrastructural characteristics of neuronal cell death by sPLA2-IIA were apoptotic, as evidenced by condensed chromatin and fragmented DNA. Before apoptosis, sPLA2-IIA liberated arachidonic acid (AA) and generated prostaglandin D2 (PGD2), an AA metabolite, from neurons. Indoxam significantly suppressed not only AA release, but also PGD2 generation. Indoxam prevented neurons from sPLA2-IIA-induced neuronal cell death. The neuroprotective effect of indoxam was observed even when it was administered after sPLA2-IIA treatment. Furthermore, a cyclooxygenase-2 inhibitor significantly prevented neurons from sPLA2-IIA-induced PGD2 generation and neuronal cell death. In conclusion, sPLA2-IIA induces neuronal cell death via apoptosis, which might be associated with AA metabolites, especially PGD2. Furthermore, sPLA2 contributes to neurodegeneration in the ischemic brain, highlighting the therapeutic potential of sPLA2-IIA inhibitors for stroke.     

A quantitative evaluation of pontine volume by computed tomography in patients with cerebellar degeneration

We used CT to make a quantitative evaluation of the pontine volumes of 55 patients with adult-onset cerebellar degeneration and compared the results with their clinical records. Patients with pontine atrophy showed significantly more autonomic dysfunction and extrapyramidal signs; their other clinical features did not differ from patients without pontine atrophy. After dividing the patients into 2 groups, those with and without autonomic dysfunction or extrapyramidal signs, we found that those with these manifestations also had pontine atrophy, a later onset and shorter duration of the disease, and impairment of higher brain functions. The group without these manifestations had relatively normal pontine volume, a greater familial tendency for cerebellar degeneration, and longer duration of the disease. Our results suggest that quantitative volume evaluation of the pons by CT is important for the clinical categorization of cerebellar degeneration.     

Effect of Euro-Collins' or UW solution on the early graft function following cadaveric kidney transplantation

From November 1985 to March 1990, 55 cadaveric kidney transplants were performed under cyclosporine therapy. All kidneys were harvested from non-heart beating donors and cold stored after being flushed with EC solution (Group I, n = 27) or UW solution (Group II, n = 28). Warm ischemic time (min) in groups I and II were 7.1 +/- 3.3 and 6.9 +/- 2.3, respectively. Cold ischemic times (hr) in groups I and II were 6.9 +/- 2.4 and 8.4 +/- 2.8, respectively. Mean numbers of days for postoperative dialysis were 14.0 +/- 7.9 in group I and 7.9 +/- 5.8 in group II (p less than 0.05). One-month creatinine (mg/dl) was 2.9 +/- 2.8 in group I and 1.75 +/- 1.0 in group II (NS). One-month graft survivals (%) in groups I and II were 81.4% and 92.8%, respectively. In conclusion, UW solution has provided beneficial effect of preservation on ischemic damaged kidney and appears to be method of choice in non-heart beating cadaveric kidney transplantation.     

Intrahepatic micrometastases around liver metastases from gastric cancer

Background/Purpose  We aimed to clarify the association between the presence of micrometastases around liver metastases from gastric cancer and the results of hepatic resection. In addition, we investigated the influence of E-cadherin and matrix metalloproteinase (MMP)-7 expression on the development of micrometastases. Methods  Micrometastases around liver metastases were examined microscopically in 31 metastatic liver tumor specimens resected from 17 patients who had undergone hepatic resection for liver metastases from gastric cancer. E-cadherin and MMP-7 expression in the primary gastric tumor, the liver metastases, and the micrometastases were examined immunohistochemically. Results  Hepatic micrometastases were present in around 48% of the liver metastases, accounting for 59% of the patients. The tumor recurrence rate in the remnant liver after hepatic resection was significantly higher, and survival significantly poorer, in patients with such micrometastases than in those without. Micrometastases tended to appear around the liver metastases that had reduced E-cadherin expression. Most of the micrometastases in the lymph ducts and sinusoids showed reduced E-cadherin expression. MMP-7 expression was not correlated with the presence of micrometastases. Conclusions  About half of the hepatic metastases from gastric cancer had seeded off micrometastases, and the presence of these micrometastases was associated with a poorer result of hepatic resection. Reduced E-cadherin expression in metastatic liver tumors may be associated with the development of micrometastases.     

Effect of scanner type on the reproducibility of extracoronary measures of calcification: the multi-ethnic study of atherosclerosis

RATIONALE AND OBJECTIVES: Cardiac computed tomography (CT) has been used extensively to measure coronary artery calcification. However, extracoronary calcifications, such as aortic valve calcification (AVC), may have independent clinical significance as well. The ability to track calcification is dependent on the reproducibility of the original measurement, and the variability of extracoronary calcification measurements still is unknown. Accurate quantification of calcification of the aortic valve, mitral annulus (MAC), and thoracic aortic (TAC) may be possible by using cardiac CT. METHODS: A total of 1,729 randomly chosen participants (ages 45-84, 53% female, 28% African-American, 36% Caucasian, 11% Chinese, 25% Hispanic) of the Multi-Ethnic Study of Atherosclerosis underwent dual scanning by electron beam CT (EBT) or multidetector CT (MDCT) to assess coronary and extra-coronary calcifications. Two calcium measurement methods--Agatston score (AS) and volume score (VS)--were measured for each scan. Concordance for calcium positivity was assessed among all scans. Mean absolute and relative differences between calcium measures on scans 1 and 2, excluding cases for which both scans had a measure of zero, was modeled by using linear regression to compare variability between scanner types. A repeated measures analysis of variance test was used to compare variability across calcium measures, with mean percentage absolute difference as the outcome measure. RESULTS: Concordances for the presence of calcium between duplicate scans were high and similar for both EBT and MDCT. Concordance was high for all three extracoronary measures, with a kappa statistic of kappa = 0.94-0.96. For all three extracoronary sites, Bland-Altman plots demonstrated excellent agreement, with almost all measures falling within the boundaries of the 95% confidence limits of reproducibility. AVC interscan variability was approximately 8% for both AS and VS, with improved variability for EBT as compared with MDCT. Mitral annular calcification demonstrated slightly lower variability than AVC for both scanner types (approximately 6%), with no significant differences between MDCT and EBT. Of the three extracoronary sites, TAC had the highest variability (10%), with MDCT variability slightly lower than EBT variability (9.3 vs. 10.2%, respectively, P = NS). Agatson and volume scores for each of the three extracoronary sites were similar. CONCLUSIONS: Overall rescan measurement variabilities for extracoronary calcification are low and should not be an impediment to the use of this test for studying progression of extracoronary calcification over time.     

Adult T-cell leukemia/lymphoma with multiple integration of HTLV-1 provirus presenting as an isolated paranasal sinus tumor: a case report

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoma and etiologically associated with human T-lymphotropic virus type 1 (HTLV-1). Patients with ATLL commonly present with leukemic changes, systemic lymphadenopathy, and/or extranodal lesion and have very poor prognosis. METHODS AND RESULTS: We describe a rare case of ATLL presenting as an isolated paranasal mass. Southern blot analysis of the biopsied specimens demonstrated multiple integration bands of HTLV-1 provirus of different intensities. Chemotherapy resulted in complete resolution of the paranasal mass. Thereafter, the patient showed an indolent clinical course with leukemic changes and pulmonary and cutaneous ATLL lesions and remains alive more than 5 years from diagnosis. CONCLUSION: ATLL should be included in the differential diagnosis of sinonasal lymphoma, although the event is rare. Multiple HTLV-1 provirus integrations of different intensities may be indicative of good prognosis for ATLL.