Anti-macrophage monoclonal antibody D-11 in the diagnosis of histiocytic tumors

Anti-macrophage monoclonal antibody (Mab) D-11 was tested in surgical material and biopsies of non-epithelial tumors and tumor-like lesions from 181 patients in order to assess possibility of using this Mab for diagnosis of histiocytic tumors, malignant fibrous histiocytoma in particular. The study was performed in parallel on cryostat sections and smears by immuno-peroxidase method. It is established that D-11 reacts positively with both histiocytic tumors and tumors of other genesis this being a limiting factor in differential diagnosis of histiocytic tumors. However, taking into consideration 100% of positive results with histiocytic tumors only, this antibody can be used for exclusion of tumors studied from the group of histiocytomas in cases of negative reaction.     

Legal issues in sharing the benefits of biodiversity prospecting

The National Cancer Institute (NCI) is the US Government's principal agency for research on the prevention, diagnosis and treatment of cancer. A critical component of the Institute's mission is the identification and development of new and promising treatments for cancer and AIDS. For many years these efforts have included a program to investigate natural products for potential new therapeutic agents. In 1986, with the advent of new screening techniques, the National Cancer Institute stepped up its exploration of natural products and began world-wide collections of plants in tropical and subtropical regions. In recognition of the principles of the Biodiversity Treaty, NCI appreciates that continued access to the natural products of these countries depends on the Institute's ability to recognize the contributions of these source countries and their indigenous peoples, and to provide them adequate incentives to conserve their natural resources for the purposes of drug discovery. Accomplishing this goal presented several legal issues for the National Cancer Institute. As an agency of the US government, the NCI has an adjunct statutory mission to facilitate the transfer of technology developed through the Institute's programs into the private sector for further development and commercialization, and NCI operates under a national policy to use the patent system to transfer Federally supported research to the private domestic sector. Reliance on patent law may limit the Institute's ability to recognize the rights of source countries and their indigenous people and provide compensation for their contributions. However, other legal instruments, such as contracts, can serve as interim measures to provide compensation to source countries and indigenous populations. The National Cancer Institute's Letter of Collection agreement (LOC, formerly the "Letter of Intent'), is an example of an alternative means that "fills-in the gaps' created by patent law and through which source countries may share in the benefits of natural product development.     

Developmental and behavioral effects of prenatal primidone exposure in the rat

Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-17 in doses of 0.40, and 80 mg/kg. Although these doses of PRM did not produce significant differences in litter size, birth weight, mortality, date of attainment of developmental landmarks or measures of preweaning reflex and motor development, there were a number of significant differences that developed as the animals approached and entered adulthood. When tested as adults, the 80 mg/kg male rats showed a deficit in the performance of an eight-arm radial maze task. These same animals showed a significant reduction in open field activity when tested as adults. In addition, both male and female PRM-treated animals showed reduced body weights at different periods corresponding to onset of sexual maturation during development. These findings are consistent with the larger body of literature reporting on the neurobehavioral teratology of phenobarbital, including its ability to produce lesions in the hippocampus and endocrine dysfunction resulting in reproductive deficits. These results suggest that PRM produces its adverse effects as a result of its metabolism to phenobarbital, which in turn affects the limbic system.     

Accuracy of single-photon emission computed tomography myocardial perfusion imaging in patients with stents in native coronary arteries

Strategies to noninvasively evaluate patients after coronary stenting have not been evaluated. To determine the accuracy of single-photon emission computed tomography (SPECT) myocardial perfusion imaging in patients after coronary stenting, 209 patients who had undergone stenting followed by late stress SPECT myocardial perfusion imaging were evaluated. Quantitative coronary angiography was performed in 33 patients following SPECT imaging. SPECT restenosis was defined as a reversible or fixed defect within the stented vascular territory. Angiographic restenosis was examined using 2 definitions: total area narrowing > or =50% or > or =70% of the stent site or stented artery. The SPECT and angiographic findings were concordant in 22 of 33 stented vascular territories using the 50% definition of restenosis and in 29 of 33 stented territories using the 70% definition. Use of the 70% definition of restenosis resulted in improved accuracy of SPECT to detect a significant stenosis in the stented artery. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SPECT were 95%, 73%, 88%, 89%, and 88% respectively. In patients with positive SPECT scans, the most significant stenosis in the stented artery was outside the stent site in 50% of cases. SPECT imaging appears to be accurate to predict significant stenosis in the stented artery, although the most severe stenosis is frequently distant from the stent site.     

5-HPETE is a potent inhibitor of neuronal Na+, K(+)-ATPase activity

The effects of 1 microM concentrations of arachidonic acid hydroperoxide (HPETES) products of 5-, 12- and 15-lipoxygenase on Na+, K(+)-ATPase activity were investigated in synaptosomal membrane preparations from rat cerebral cortex. 5-HPETE inhibited Na+, K(+)-ATPase activity by up to 67 %. In contrast, 12-HPETE and 15-HPETE did not inhibit Na+, K(+)-ATPase activity. In addition, neither 5-HETE or LTA4 inhibited Na+, K(+)-ATPase activity. Dose-response studies indicated that 5-HPETE was a potent (IC25 = 10(-8) M) inhibitor of Na+, K(+)-ATPase activity. These findings indicate that 5-HPETE inhibits Na+, K(+)-ATPase activity by a mechanism that is dependent on the hydroperoxide position and independent of further metabolism by 5-lipoxygenase. It is proposed that 5-HPETE production by 5-lipoxygenase and subsequent inhibition of neuronal Na+, K(+)-ATPase activity may be a mechansim for modulating synaptic transmission.     

The effect of changing excitation frequency on parallel conductance in different sized hearts

OBJECTIVE: An important component of the ventricular volume measured using the conductance catheter technique is due to parallel conductance (Vc), which results from the extension of the electric field beyond the ventricular blood pool. Parallel conductance volume is normally estimated using the saline dilution method (Vc(saline dilution)), in which the conductivity of blood in the ventricle is transiently increased by injection of hypertonic saline. A simpler alternative has been reported by Gawne et al. [12]. Vc(dual frequency) is estimated from the difference in total conductance measured at two exciting frequencies and the method is based on the assumption that parallel conductance is mainly capacitive and hence is negligible at low frequency. The objective of this study was to determine whether the dual frequency technique could be used to substitute the saline dilution method to estimate Vc in different sized hearts. METHODS: The accuracy and linearity of a custom-built conductance catheter (CC) system was initially assessed in vitro. Subsequently, a CC and micromanometer were inserted into the left ventricle of seven 5 kg pigs (group 1) and six 50 kg pigs (group 2). Cardiac output was determined using thermodilution (group 1) and an ultrasonic flow probe (group 2) from which the slope coefficient (alpha) was determined. Steady state measurements and Vc estimated using saline dilution were performed at frequencies in the range of 5-40 kHz. All measurements were made at end-expiration. Finally, Vc was estimated from the change in end-systolic conductance between 5 kHz and 40 kHz using the dual frequency technique of Gawne et al. [12]. RESULTS: There was no change in measured volume of a simple insulated cylindrical model when the stimulating frequency was varied from 5-40 kHz. Vc(saline dilution) varied significantly with frequency in group 1 (8.63 +/- 2.74 ml at 5 kHz; 11.51 +/- 2.65 ml at 40 kHz) (p = 0.01). Similar results were obtained in group 2 (69.43 +/- 27.76 ml at 5 kHz; 101.24 +/- 15.21 ml at 40 kHz) (p < 0.001). However, the data indicate that the resistive component of the parallel conductance is substantial (Vc at 0 Hz estimated as 8.01 ml in group 1 and 62.3 ml in group 2). There was an increase in alpha with frequency in both groups but this did not reach significance. The correspondence between Vc(dual frequency) and Vc(saline dilution) methods was poor (group 1 R2 = 0.69; group 2 R2 = 0.22). CONCLUSION: At a lower excitation frequency of 5 kHz a smaller percentage of the electric current extends beyond the blood pool so parallel conductance is reduced. While parallel conductance is frequency dependent, it has a substantial resistive component. The dual frequency method is based on the assumption that parallel conductance is negligible at low frequencies and this is clearly not the case. The results of this study confirm that the dual frequency technique cannot be used to substitute the saline dilution technique.     

Ultrastructural features of diffuse malignant mesotheliomas

The distinction of malignant mesothelioma from tumors metastatic to the serosal membranes can often be made based on the results of histochemical or immunohistochemical studies. However, in some cases, these techniques are inadequate to make a firm diagnosis. In these instances, electron microscopic studies with the observation of a constellation of characteristic ultrastructural findings may permit an unequivocal diagnosis of mesothelioma.