Reperfused myocardial infarctions on T1- and susceptibility-enhanced MRI: Evidence for loss of compartmentalization of contrast media

The purpose of this study was to characterize the contrast caused by a susceptibility MRI contrast agents, on spin echo T₂-weighted imaging of reperfused myocardial infarction. Our interest in this model focused on the expected requirement that such agents be compartmentalized in the tissue to cause signal loss on spin echo images, a condition which may not be present in reperfused infarcted myocardium. Accordingly, nine rats were subjected to 2 h of left coronary artery occlusion followed by 3 ± 0.5 h of reperfusion prior to administration of contrast media. Three sets of MR images were acquired: (a) baseline axial images at the midventricle, both T₁-weighted (TR/TE = 300/20) and T₂-weighted (TR/TE = 1500/60); (b) T₁-weighted images after administering a T₁-enhancing agent, Gd-DTPA-BMA (0.2 mmol/kg), to document that contrast media is delivered to the reperfused infarction; and (c) T₂-weighted images after administering the susceptibility agent, Dy-DTPA-BMA (1.0 mmol/kg). Gadolinium-enhanced T₁ images depicted reperfused infarction as regions with greatly enhanced signal intensity compared with unin-farcted myocardium, indicating that contrast agent was delivered to the infarcted zone. Dysprosium-enhanced T₁ images depicted the injury as a region of persistent signal intensity relative to depletion of signal in normal myocardium, consistent with failure of the contrast agent to cause signal loss. Similar infarction sizes were observed for unenhanced T₂-weighted images (33 ± 5%), gadolinium-enhanced T₁ weighted images (36 ± 5%) and postmortem staining (30 ± 6%); strong correlations (r > 0.9) were noted in comparisons of these data. Dysprosium-enhanced images exhibited a smaller region of differential signal presumed to be infarction (20 ± 5%, P < 0.05) and weak correlations (r < 0.75) with the other measurements. We conclude that the smaller infarction depicted on dysprosium-enhanced images is a subregion of the true infarction in which myocardial necrosis is sufficiently advanced that the agent is homogeneously distributed throughout all tissue compartments, preventing T₂*-dependent phase loss on spin echo images.     

A CASE OF METASTATIC YOLK SAC TUMOR OF TESTIS IN A CHILD

We report a case of testicular yolk sac tumor in a child aged 3 years and 6 months with multiple bulky metastases to lung and retroperitoneum (stage 11182). After three courses of chemotherapy with a PV 8 regimen (cisplatin, vinblastine and bleomycin). complete and partial responses were obtained for lung and retroperitoneal lymph node metastases, respectively. The patient was followed-up closely. However, on the basis of a re-elevated alpha-letoprotein (AFP) after 4 months' follow-up, he was treated with three courses of salvage chemotherapy with a modified VAB-6 regimen (cyclophosphamide. etoposide. actinomycin D, bleomycin and cisplatin), lollowed by retroperitoneal lymph node dissection. Histologically, only necrotic tissue was found. There is no evidence of recurrence 24 months after lymphadenectomy. There is very little information in the literature on the appropriate management of postchemotherapy residual mass in pediatric testicular tumors.     

Cerebral type of Lewy body disease

A cerebral type of Lewy body disease (LBD) is proposed. Lewy body disease was split formerly into three types: brainstem type, transitional type and diffuse type. The diffuse type is now called diffuse Lewy body disease (DLBD). These three types are characterized pathologically by the presence of a large number of Lewy bodies in the CNS. In the brainstem type, Lewy bodies are numerous in the brainstem and diencephalon nuclei, and in DLBD, a vast number are present not only in these nuclei but also in the cerebral cortex and amygdala. In the cerebral type of LBD, as many Lewy bodies are found in the cerebral cortex and in the amygdala as there are in DLBD, but only rarely are they present in the brainstem and diencephalon nuclei. Thus, this type of LBD is different from other types in that it has no parkinson pathology. Therefore, parkinsonism fails to occur throughout the whole clinical course of this disease. The existence of a cerebral type of LBD suggests that Lewy bodies occur in the cerebral cortex earlier than in the brainstem nuclei and that cortical Lewy bodies appear even when the mesocortical dopaminergic system is intact. In addition, this might explain why dementia frequently precedes parkinsonism in DLBD.     

Measurement of airway resistance in anesthetized and paralyzed subjects: Proposal for evaluation of K1 values

The effects of lung volume and respiratory airflow on airway resistance were studied in five anesthetized and paralyzed patients. Airway resistance measured during the inspiratory phase with intermittent constant airflow inflatoins decreased in inverse correlationship to increases in lung volume. Airway resistance measured during the expiratory phase with an airway interruption technique, on the other hand, increased with a linear relationship to the expiratory airflow as expressed by a function of Y = K₁ + K₂X. K₁, calculated from the values of airway resistance corresponding to three different airflows, was unaffected by intentional expiratory resistance loading. Thus, simultaneously with the measurement of airway resistance by this method, expiratory gas sampling with a Douglas bag can be done if necessary. Since the K₂ value of the endotracheal tube used in this study (Portex^® I.D. 8mm, length 26cm) was quite high (5.0cmH₂O·1^–2·sec²), depending on the airflow, the presence of the endotracheal tube strongly affected the measurement of airway resistance during general anesthesia. K₁ measured by the above method, however, may be considered as the best way to evaluate the lower airway resistance independent of either lung volume or expiratory airflow.(Sakai T, Yoshida H, Yano H et al.: Measurement of airway resistance in anesthetized and paralyzed subjects: proposal for evaluation of K₁ values. J Anesth 2: 139–145, 1988)     

Immunoglobulin G from anti-glucose-6-phosphate isomerase antibodies positive patient with rheumatoid arthritis induces synovitis in cynomolgus monkeys

Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) solely induce arthritis in mice. High titers of anti-GPI Abs are found in some patients with rheumatoid arthritis (RA), but their pathogenic role remains elusive. The aim of this study was to evaluate the pathogenic role of anti-GPI Abs in cynomolgus monkeys. IgG fractions were separated from sera of anti-GPI Abs-positive RA patients and healthy subjects and directly injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. At day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from monkey joints. In monkey joints, IgG including anti-GPI Abs resulted in recruitment of granulocytes and mononuclear cells, strong deposition of human IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients including anti-GPI Abs may play a crucial role in the generation of synovitis in monkeys, although the pathogenesis of anti-GPI Abs in RA patients is still uncertain.     

Lattices of Type I Collagen Select Invasive Variants of K-ras Oncogene-Transfected NIH3T3 with Less Cellular fibronectin

A clone of NIH3T3 transformant (H3) can yield subcutaneous tumors and experimental pulmonary metastasis in nude mice. Compared to H3 in culture, the cells after in vivo tumor growth (H3-N) acquired enhanced tumorigenicity and metastatic ability. Also, indirect immunofluorescence revealed that cellular fibronectin (c-FN) of H3-N was decreased remarkably. We have studied the interactions between H3 and extracellular matrices to elucidate these phenomena. In the present study, we observed the effect of NIH3T3, H3, and H3-N cultured in type I collagen gel. Morphologically in the collagen gel, NIH3T3 assumed an extensive elongated fiber-like shape, H3 assumed a moderately elongated shape, and H3-N assumed a round or spindle shape with short pseudopodia. Compared to conventional cultures on dishes, cell proliferation of all three types was suppressed in collagen gel, but the degree of the suppression was least in H3-N. As a result, H3-N grew fastest in collagen gel. The variants which acquired growth advantage in the subcutaneum of mice also kept it in collagen gel. H3 cells were cultured in type I collagen gel for 4 weeks, a period comparable to that of tumor formation in nude mice. The cells after this long-term culture (H3-C) acquired enhanced tumorigenicity and metastatic ability nearly equal to that of H3-N. FACS analysis revealed that the c-FN of H3-C had decreased to a value comparable to that of H3-N. This means that type I collagen gel as well as subcutaneous tissues could select variants of H3 with less c-FN through proliferation. Moreover, it is suspected that lattices of type I collagen regulate cell proliferation of fibroblast via c-FN. This revised version was published online in August 2006 with corrections to the Cover Date.     

Fibrinogen stabilizes placental-maternal attachment during embryonic development in the mouse

In humans, maternal fibrinogen (Fg) is required to support pregnancies by maintaining hemostatic balance and stabilizing uteroplacental attachment at the fibrinoid layer found at the fetal-maternal junction. To examine relationships between low Fg levels and early fetal loss, a genetic model of afibrinogenemia was developed. Pregnant mice homozygous for a deletion of the Fg-gamma chain, which results in a total Fg deficiency state (FG(-/-)), aborted the fetuses at the equivalent gestational stage seen in humans. Results obtained from timed matings of FG(-/-) mice showed that vaginal bleeding was initiated as early as embryonic day (E)6 to 7, a critical stage for maternal-fetal vascular development. The condition of afibrinogenemia retarded embryo-placental development, and consistently led to abortion and maternal death at E9.75. Lack of Fg did not alter the extent or distribution pattern of other putative factors of embryo-placental attachment, including laminin, fibronectin, and Factor XIII, indicating that the presence of fibrin(ogen) is required to confer sufficient stability at the placental-decidual interface. The results of these studies demonstrate that maternal Fg plays a critical role in maintenance of pregnancy in mice, both by supporting proper development of fetal-maternal vascular communication and stabilization of embryo implantation.     

C and V proteins of Sendai virus target signaling pathways leading to IRF-3 activation for the negative regulation of interferon-beta production

We here report a molecular basis for downregulation of interferon (IFN)-beta production by V and C proteins of Sendai virus (SeV). The infection of HeLa cells with SeV poorly induced IFN-beta even if the expression of C/C' was disrupted. In contrast, when the expression of C/C'/Y1/Y2 or V/W was disrupted, SeV infection strongly induced IFN-beta production and significantly activated the interferon regulatory factor (IRF)-3 pathway. The independent expression of C or V inhibited the double-stranded (ds) RNA- or Newcastle disease virus (NDV)-induced activation of IRF-3 and NF-kappa B, as well as the IFN-beta promoter. This inhibitory effect was also observed when Y1, Y2, or a C-terminal half fragment (aa 85-204) of C was independently expressed. Phosphorylation and homodimer formation of IRF-3 were suppressed not only in cells infected with SeV capable of expressing both C/C'/Y1/Y2 (or Y1/Y2) and V/W, but also in HeLa cells constitutively expressing Y1. These results suggest that C, Y1, Y2, and V block signaling pathways leading to IRF-3 activation to downregulate IFN-beta production.