Deoxyribonucleic acid flow cytometry of squamous cell carcinoma of the penis

This article reports 10 cases of cranial base tumors resected by pre-or retro-auricular intratemporal approach. Among them four were neuronomas, two meningiomas, one malignant giant cell tumor of bone, one osteochondnoma, one parotid mixed neoplasm and one poorly-differentiated squamors cell carcinoma. Total resection in 9 cases and one subtotal resection were performed without operative mortality and serious surgical complications. The surgical management of cranial base tumor and indications for selecting operative approaches were discussed.     

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), a novel bis-naphthalimide with potent nonselective tumoricidal activity in vitro

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), is a bis-naphthalimide anticancer tumoricidal agent currently in phase I clinical trials. DMP 840 exhibits curative activity in human tumor xenografts, where it shows selectivity for human solid tumors over murine leukemias. In contrast to the selectivity found for DMP 840 in vivo, DMP 840 exhibits potent antiproliferative activity in vitro against a variety of human and murine leukemia and solid tumor cell lines in culture, with inhibitory doses that reduce the number of treated cells to one half (IC50) values ranging from 2.3 to 53 nM. DMP 840 was growth inhibitory to three doxorubicin-resistant cell lines with IC50 values also in the nanomolar range. Clonogenic survival experiments showed that DMP 840 was equally cytotoxic to both exponentially growing and quiescent human clone A colon carcinoma cells. A 1-h incubation of DMP 840 (1.22-12 microM) caused 5-log cell kill in KB-3-1 human epidermoid carcinoma, clone A human colon carcinoma, and L1210 murine leukemia cell lines. The rapid cell killing by DMP 840 in clonogenic survival experiments and initial mechanism of action studies was consistent with a DNA-interactive mechanism for DMP 840 cytotoxicity. Mechanism of action studies in L1210 leukemia cells demonstrated that DMP 840 inhibited the incorporation of thymidine and uridine into DNA and RNA with IC50 values of 0.55 and 0.08 microM, respectively. DMP 840 produced DNA single-strand breaks in a dose-dependent manner. Double-strand breaks were not observed with DMP 840 treatment, even at higher concentrations of compound. Chinese hamster ovary (CHO) and P388 cells resistant to camptothecin and containing a mutant form of topoisomerase I were also used to evaluate whether DMP 840 was cross-resistant with agents active against topoisomerase I. While the CHOR line was 163-fold resistant to camptothecin, the CHOR line was only 1.7-fold resistant to DMP 840. In summary, DMP 840 is a DNA-interactive agent that demonstrates excellent antiproliferative activity in vitro against cultured tumor cells from both human and murine sources. Its mechanism of tumoricidal activity may be novel.     

Demonstration of delayed hypersensitivity in Chlamydia trachomatis salpingitis in monkeys: a pathogenic mechanism of tubal damage

The role of delayed hypersensitivity in the pathogenesis of Chlamydia t trachomatis salpingitis was studied in the monkey "pocket" model. Pigtailed monkeys (Macaca nemestrina) were sensitized by inoculation of live C. trachomatis organisms (E/UW-5/Cx) into subcutaneous pockets containing salpingeal autotransplants. At 21 days, affinity-purified recombinant C. trachomatis heat-shock protein (rhsp60) was injected into pockets either previously sensitized with C. trachomatis or not sensitized in the same monkey. Delayed-type hypersensitivity reaction was observed, characterized by mononuclear cell infiltration with peak reaction at 48 h. Injection of rhsp60 into the pockets of a naive animal did not induce inflammation. This study showed that C. trachomatis infection in monkeys induced delayed hypersensitivity, which is mediated by hsp60. Histologic findings of the salpinx were consistent with delayed hypersensitivity reaction observed in ocular C. trachomatis infection, further suggesting a similar pathogenesis for both salpingitis and trachoma.     

Symptomatic subclavian steal syndrome four decades after operation for dysphagia lusoria

Congenital abnormalities of the aortic arch may lead to signs and symptoms of tracheal and esophageal obstruction secondary to a restrictive vascular ring. There are many case reports and monographs concerning the surgical management of dysphagia lusoria. This case provides the first example of long-term follow-up of surgical intervention for relief of dysphagia lusoria. A 45-year-old laborer presented with a several year history of episodic bilateral blindness and a more recent onset of "drop attacks." Notably this patient had presented at the age of 18 months with difficulty breathing and eating since birth. The patient also had frequent upper respiratory infections and episodes of pneumonia. Workup revealed a right-sided aortic arch with a left ligamentum arteriosum. When he was first seen in our clinic, history and physical examination revealed claudication and diminished pulses in the left upper extremity. Arteriography and duplex studies confirmed reversal of flow in the patient's left vertebral artery. The arteriogram demonstrated the presence of a right-sided aortic arch and descending aorta along with the proximal stump of the previously ligated left subclavian artery. He underwent left carotid to left axillary artery bypass for the treatment of symptomatic subclavian steal syndrome. His symptoms have resolved with return of antegrade vertebral flow and the presence of normal pulses in the left arm. Congenital aortic abnormalities that lead to tracheal and esophageal compromise are numerous and varied. Surgical management requires a thorough understanding of the person's anatomy and preoperative planning. The life expectancy of patients with dysphagia lusoria necessitates consideration of the long-term consequences of surgical intervention.     

Co-capping studies reveal CD8/TCR interactions after capping CD8 beta polypeptides and intracellular associations of CD8 with p56(lck)

A reaction-diffusion model was developed to predict the fate of nitric oxide (NO) released by cells of the immune system. The model was used to analyze data obtained previously using macrophages attached to microcarrier beads suspended in a stirred vessel. Activated macrophages synthesize NO, which is oxidized in the culture medium by molecular oxygen and superoxide (O2-, also released by the cells), yielding mainly nitrite (NO2-) and nitrate (NO3-) as the respective end products. In the analysis the reactor was divided into a "stagnant film" with position-dependent concentrations adjacent to a representative carrier bead and a well-mixed bulk solution. It was found that the concentration of NO was relatively uniform in the film. In contrast, essentially all of the O2- was calculated to be consumed within approximately 2 microm of the cell surfaces, due to its reaction with NO to yield peroxynitrite. The decomposition of peroxynitrite caused its concentration to fall to nearly zero over a distance of approximately 30 microm from the cells. Although the film regions (which had an effective thickness of 63 microm) comprised just 2% of the reactor volume and were predicted to account for only 6% of the NO2- formation under control conditions, they were calculated to be responsible for 99% of the NO3- formation. Superoxide dismutase in the medium (at 3.2 microM) was predicted to lower the ratio of NO3- to NO2- formation rates from near unity to <0.5, in reasonable agreement with the data. The NO3-/NO2- ratio was predicted to vary exponentially with the ratio of O2- to NO release rates from the cells. Recently reported reactions involving CO2 and bicarbonate were found to have important effects on the concentrations of peroxynitrite and nitrous anhydride, two of the compounds that have been implicated in NO cytotoxicity and mutagenesis.     

Long-term socioeconomic outcome following surgical intervention in the treatment of refractory epilepsy in childhood and adolescence

Surgical treatment of refractory epilepsy in childhood and adolescence has been shown to be effective in reducing the seizure frequency. This paper examines the question: "Does this result in a better socioeconomic outcome in later years?" Patients who underwent a surgical procedure for the treatment of their medically refractory epilepsy at our hospital, had more than 2-years' follow-up, and were less than 18 years old at time of survey were included. From a retrospective chart review, age at onset and at surgery, duration of seizures prior to surgery, years of follow-up, type of surgery, and neurological status were obtained. From a telephone survey, seizure frequency after surgery, marital, financial and driving status, level of education, and employment status were ascertained. Sixty-four patients in our epileptic surgical series meet entry criteria. Significantly higher levels of education, employment status and independence were found in patients with a class I Engel outcome compared to other Engel outcomes.     

Evaluating medication response in ADHD: cognitive, behavioral, and single-subject methodology

We introduce a novel application for linkage analysis: using bone marrow donor-recipient sib pairs to search for genes influential in graft-versus-host disease (GVHD), a major cause of morbidity and mortality following allogeneic bone marrow transplantation. In particular, we show that transplant sib pairs in which the recipient developed severe GVHD can be used to map genes in the same way as traditional discordant (affected/unaffected) sib pairs (DSPs). For a plausible GVHD model, we demonstrate that the transplant/discordant sib pair analog of the "possible triangle test" [Holmans (1993) Am J Hum Genet 52:362-374] has similar power to that of the simpler "restricted test" proposed by Risch [(1990b) Am J Hum Genet 46:229-241; (1992) Am J Hum Genet 51:673-675]. Moreover, we show that the restricted test has superior power in much of the DSP possible triangle and significantly inferior power in only a small region. Thus, we conclude that the restricted test is preferable for localizing genes with transplant/discordant sib pairs. Finally, we examine the effects of heterogeneity on the power to detect GVHD loci and demonstrate the gain in efficiency by dividing the sample into genetically more homogeneous subgroups.     

Methane detection with a narrow-band source at 3.4 µm based on a Nd:YAG pump laser and a combination of stimulated Raman scattering and difference frequency mixing

We report the characterization of a 10-Hz pulsed, narrow-band source that is coincident with a fundamental ν(3) rovibrational absorption of methane at 3.43 μm. To generate this midinfrared wavelength, an injection-seeded 1.06-μm Nd:YAG laser is difference frequency mixed with first Stokes light generated in a high-pressure methane cell (1.06 ? 1.54 μm) to result in light at a wavelength of 3.43 μm, that is, the ν(1) Raman active frequency of methane (~2916.2 cm(-1)). With a modest-energy Nd:YAG laser (200 mJ), a few millijoules of this midinfrared energy can be generated with a pulse width of ~7 ns (FWHM). The methane ν(1) frequency can be pressure tuned over 8-32 atm (corresponding to ~13 GHz) and scanned across part of the ν(3)P(10) rovibrational level of methane, resulting in a peak measured methane absorption coefficient of 4.2 cm(-1) atm(-1).     

Protein topology of presenilin 1

Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we examined the binding of antibodies to specific PS1 epitopes in cultured cells selectively permeabilized with the pore-forming toxin, streptolysin-O. We document that the "loop," N-terminal, and C-terminal domains of PS1 are oriented toward the cytoplasm.     

Stability of linear discrete switched systems with delays based on average dwell time method

This paper deals with the problem of exponential stability for a class of linear discrete switched systems with constant delays.The switched systems consist of stable and unstable subsystems.Based on the average dwell time method, some switching signals will be found to guarantee exponential stability of these systems.The explicit state decay estimation is also given in the form of the solutions of linear matrix inequalities(LMIs).An example relating to networked control systems(NCSs) illustrates the effect...