Vitreous seeds in retinoblastoma,clinical significance and ultrastructure

Vitreous seeds in retinoblastoma were studied clinically and pathologically. Vitreous seeds were found in 36.6% of retinoblastoma eyes. When tumors involved more than three quadrants of the retina and vitreous seeds were present, the prognosis was poor. When the tumor involved less than one-quarter of the retina, vitreous seeds were rare. Vitreous seeds were found most frequently in cases of undifferentiated tumor cells and endophytum type of proliferation. Although most vitreous seeds were necrotic tumor cells, some were almost intact tumor cells which were apt to be situated along blood vessels. The blood vessels in vitreous seeds had no pericytes and were derived from the tumor itself. Thus it is possible that tumor cells in the vitreous body can migrate to the anterior segment of the eye. Some tumor cells in vitreous seeds had much cytoplasm which contained mitochondria, ribosomes, fibrils, centrioles, and cilia with a presumed photoreceptor outer segment and intercellular junctions. These cytoplasmic features are very similar to those of neuroepithelial-type retinoblastoma cells. Undifferentiated cells were necrotic. Calcium deposition was found mainly in the necrotic cytoplasm of the tumor cells and occasionally on the chromatin granules of the nucleus. This may provide evidence that calcium can be bound to DNA to form radiopaque masses. No calcium-producing cells were found. Vitreous seeds contain a small number of almost intact tumor cells which are neuroepithelial in type, but most cells are necrotic. Although tumor cells may migrate to the anterior segment of the eye along or through blood vessels, the presence of vitreous seeds in itself is not always a bad prognostic sign. The prognosis is probably more closely related to the extent of the invasion of a tumor associated with vitreous seeds.     

Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid-to-late pregnancy loss

AIM: Associations have been reported between antiphospholipid antibodies (aPL), mainly anticardiolipin antibodies (aCL) and/or the lupus anticoagulant, and recurrent pregnancy losses (RPL). However, relatively few studies describing antiphosphatidylethanolamine antibodies (aPE) have been reported. We describe the prevalence of aPL to both cardiolipin and phosphatidylethanolamine in patients with RPL. METHODS: Patients with recurrent early pregnancy losses (n = 145) and mid-to-late pregnancy loss(es) (n = 26) were screened for aPE and aCL. RESULTS: In patients with recurrent early pregnancy losses, prevalence of immunoglobulin G (IgG) aPE (17.9%, P = 0.001) and immunoglobulin M (IgM) aPE (12.4%, P = 0.01) was significantly higher than in the control group. In patients with mid-to-late pregnancy loss(es), prevalence of IgM aPE (19.2%, P = 0.008) and IgG aCL (23.1%, P = 0.02) was significantly higher than in the control group. CONCLUSION: Our data suggest that aPE may be a risk factor in patients with mid-to-late pregnancy loss(es) as well as recurrent early pregnancy losses.     

Metabolic monitoring of advanced uterine cervical cancer neoadjuvant chemotherapy by using [F-18]-Fluorodeoxyglucose positron emission tomography: preliminary results in three patients

OBJECTIVE: The aim of this report is to describe the potential clinical utility of tracer [F-18]-Fluorodeoxyglucose (FDG) uptake, quantitated as a standardized uptake value (SUV) by positron emission tomography (PET), to evaluate treatment response to neoadjuvant chemotherapy (NAC) in advanced uterine cervical cancer. METHODS: We briefly describe the clinical courses of three women with advanced cervical cancer who were treated with neoadjuvant chemotherapy (NAC) prior to radical hysterectomy and who were analyzed for correlation with the decrease in tumor volume by magnetic resonance imaging (MRI), in SUV by FDG-PET, and by histologic response. RESULTS: In these individuals, tumor volume and SUV were decreased by NAC. The decrease in SUV by FDG-PET was better correlated to histologic response for NAC than MRI was in advanced cervical cancer. CONCLUSIONS: Measurement of SUV by FDG-PET has clinical utility in evaluating treatment response for NAC in advanced cervical cancer. Although work in this field is still in the early stages, this report demonstrates that SUV by FDG-PET has the potential to become the new standard for monitoring the treatment response of NAC in cervical cancer. This monitoring approach must be proven in a larger number of patients for both primary and secondary lesions and should be further explored in another gynecologic cancer.     

Effect of depth and tubule direction on ultimate tensile strength of human coronal dentin

The purpose of this study was to evaluate the effect of dentin depth and tubule direction on the ultimate tensile strength (UTS) of human dentin. Dentin slabs of 0.5-mm thickness were trimmed either from the mesial and distal (for specimens with the tubules parallel to the tensile force; parallel group) or from the occlusal and pulpal surfaces (perpendicular group) to reduce the cross-sectional area of the superficial, middle, and deep regions to 0.25 mm2, and subjected to microtensile testing. From SEM photomicrographs of the fractured specimens of the parallel group, the tubule density was investigated. For both parallel and perpendicular groups, superficial dentin showed a significantly higher UTS than deep dentin. The tubule density of superficial dentin was significantly lower than that of middle and deep dentin. When performing the microtensile bond test to deep dentin, it is possible that cohesive failure of dentin can occur at relatively low tensile stresses.     

Enhanced dopamine release by nicotine in cigarette smokers: a double-blind, randomized, placebo-controlled pilot study

Previous studies of smoking on dopamine release in humans were investigated only in smokers. Using nicotine gum, we examined the effect of nicotine on dopamine release in smokers and non-smokers and its relation to the degree of nicotine dependence. Smokers and non-smokers participated in a double-blind, randomized, placebo-controlled cross-over study. They participated in two PET measurements with [11C]raclopride, in which they received either nicotine or placebo. Changes in [11C]raclopride non-displaceable binding potential (BPND) following nicotine administration were quantified. Smokers showed significant decrease in BP in the striatum following nicotine administration, but non-smokers did not show such a decrease. The BPND difference between the two scanning sessions was correlated with the degree of nicotine dependence. The BPND difference might reflect enhanced dopamine release in smokers and the reinforced effect of nicotine. These data suggest the feasibility of our gum method as well as the importance of the degree of dependence in future studies of the nicotine effect on the dopamine system.     

Influenza vaccination for severely multiply handicapped persons/children in the 2005-2006 season

In this study, we report the effectiveness of trivalent inactivated influenza vaccination (TIV) for severely multiply handicapped persons/children (SMHPs) in the 2005-2006 season. In 77 SMHPs, A/New York/55/2004 (H3N2) which was the changed vaccine-strain showed significant differences in the geometric mean titers (P<0.05) and seroprotection rates (P<0.01) between pre- and post-vaccination. A/New Caledonia/20/99 (H1N1) and B/Shanghai/361/2002, which were the unchanged vaccine-strains, showed no significant differences. We defined the potential responders as those who can achieve 1:40 or more hemagglutination inhibition (HAI) titer after vaccination with any vaccine-strain. Therefore, the rate of potential responders is equivalent to the rate of seroprotection, estimated to be 40-60% among the SMHPs and >80% among the control group in this study. In the SMHPs, even potential responders could only achieve limited HAI titers (1:40-80) even after repeated vaccination. In contrast, the control group showed higher HAI titers compared to the SMHPs for the unchanged vaccine-strains caused by the priming effect. These data suggest that it might be difficult for SMHPs (including potential responders) to achieve the priming effect by the current TIV. Consequently, they cannot obtain a booster effect.     

Attenuation by intravenous 2-chloroadenosine of acute lung injury induced by live escherichia coli or latex particles added to endotoxin in the neutropenic state

Although neutrophil depletion can reduce the level of acute lung injury (ALI) induced by Escherichia coli endotoxin, that induced by live E coli cannot be attenuated even in neutropenia. This suggests that live E coli cause ALI by way of an mechanism independent of circulating neutrophil. Tumor necrosis factor-alpha (TNF-alpha), which is released from monocytes and macrophages, is a proinflammatory cytokine that is recognized as a central mediator of several forms of inflammation. In this controlled experimental study, we examined the effects of an adenosine-receptor agonist, 2-chloroadenosine (2CA), that has suppressive effects on various cell types and TNF-alpha, on endotoxin plus latex particles, and on ALI induced by live E coli in the neutropenic state. We studied 42 guinea pigs rendered neutropenic by means of intraperitoneal cyclophosphamide administration. Experimental groups consisted of (1) a saline-solution control group; (2) an endotoxin (0.2 mg/kg)-treated group; (3) a group treated with endotoxin plus 2CA (10 micro g/kg); (4) a group treated with latex (2 x 10(9)/kg); (5) a group exposed to endotoxin and latex; (6) a group exposed to endotoxin, latex, and 2CA; (7) a group exposed to E coli (2 x 10(9)/kg); and (8) a group exposed to E coli and 2CA. The injection of endotoxin alone in neutropenic animals did not increase the indexes of ALI (lung tissue/plasma ratio [T/P] and lung wet weight/dry weight ratio [W/D], calculated with the use of iodine 125-labeled albumin). In contrast, these indexes were increased in the endotoxin-and-latex groups compared with those of the control group. ALI in the endotoxin-and-latex group was attenuated by intravenous 2CA. The intravenous injection of live E coli also caused increases in T/P, W/D, and plasma TNF-alpha, but thse were limited by 2CA. In summary, ALI induced by latex particles added to endotoxin and live E coli in the neutropenic state was attenuated by 2CA, suggesting a partial contribution of various cell types or humoral mediators as a neutrophil-independent pathway in its pathogenesis.     

A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart

Marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the failing human myocardium. Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC2v), which is involved in the development of human cardiomyopathy, is an important structural protein that affects physiologic cardiac sarcomere formation and heart development. Integrated cDNA expression analysis of failing human myocardia uncovered a novel protein kinase, cardiac-specific myosin light chain kinase (cardiac-MLCK), which acts on MLC2v. Expression levels of cardiac-MLCK were well correlated with the pulmonary arterial pressure of patients with heart failure. In cultured cardiomyocytes, knockdown of cardiac-MLCK by specific siRNAs decreased MLC2v phosphorylation and impaired epinephrine-induced activation of sarcomere reassembly. To further clarify the physiologic roles of cardiac-MLCK in vivo, we cloned the zebrafish ortholog z-cardiac-MLCK. Knockdown of z-cardiac-MLCK expression using morpholino antisense oligonucleotides resulted in dilated cardiac ventricles and immature sarcomere structures. These results suggest a significant role for cardiac-MLCK in cardiogenesis.