Estramustine and estrone analogs rapidly and reversibly inhibit deoxyribonucleic acid synthesis and alter morphology in cultured human glioblastoma cells

Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's early effects on deoxyribonucleic acid synthesis in these tumors. Because estramustine shares a common structural motif with other antimicrotubule drugs, we synthesized four A-ring conjugates of estrone that contained a carbamate moiety but lacked nitrogen mustard. These analogs were examined by [3H]thymidine incorporation and compared with vinblastine. Greater than 70% inhibition of [3H]thymidine incorporation occurred within 1 hour of treatment with estramustine at 10(-5) mol/L, which increased to 80% inhibition at 4 hours. Ethyl carbamate JE208 was nearly as effective as estramustine in inhibiting deoxyribonucleic acid synthesis, and both were more effective than vinblastine. The inhibitory effects of estramustine and estrone analogs were reversible; vinblastine was not reversible. Although estramustine and JE208 induced similar antiproliferative and morphological changes in glioblastoma cells that persisted for at least 4 days, there was a modest recovery of morphology and thymidine incorporation with JE208 after prolonged treatment. The common findings with estramustine and JE208 suggest that these agents may have a similar mechanism of action and form the basis for the investigation of new agents that may rapidly and reversibly inhibit glioblastoma.     

The therapeutic effect of intralesional interferon in classical Kaposi's sarcoma

Interferon alpha-2a, which has antineoplastic, antiviral, immunomodulatory, and antiangiogenic effects, was evaluated in a prospective study, treating 10 lesions of patients with classical Kaposi's sarcoma. Ten patients received injections of interferon alpha-2a intralesionally in a dose of 3 million units three times weekly for 4 weeks, and in a variable dose for 4 more weeks. Two of the patients had a complete response, and in one of these, distant lesions also responded. Seven had a partial response, and one did not respond. The treatment was generally well tolerated. The results of our study support the use of interferon in the therapy of classical Kaposi's sarcoma, although it would appear that to achieve maximum efficacy, a longer period of treatment is needed.     

Modeling ion implantation of HgCdTe

Ion implantation of boron is used to create n on p photodiodes in vacancy-doped mercury cadmium telluride (MC.T). The junction is formed by Hg interstitials from the implant damage region diffusing into the MC.T and annihilating Hg vacancies. The resultant doping profile is n⁺/n^-/p, where the n⁺ region is near the surface and roughly coincides with the implant damage, the n^- region is where Hg vacancies have been annihilated revealing a residual grown-in donor, and the p region remains doped by Hg vacancy double acceptors. We have recently developed a new process modeling tool for simulating junction formation in MC.T by ion implantation. The interstitial source in the damage region is represented by stored interstitials whose distribution depends on the implant dose. These interstitials are released into the bulk at a constant, user defined rate. Once released, they diffuse away from the damage region and annihilate any Hg vacancies they encounter. In this paper, we present results of simulations using this tool and show how it can be used to quantitatively analyze the effects of variations in processing conditions, including implant dose, annealing temperature, and doping background.     

The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene

The acid sphingomyelinase (ASM) gene, which has been implicated in ceramide-mediated cell signaling and atherogenesis, gives rise to both lysosomal SMase (L-SMase), which is reportedly cation-independent, and secretory SMase (S-SMase), which is fully or partially dependent on Zn2+ for enzymatic activity. Herein we present evidence for a model to explain how a single mRNA gives rise to two forms of SMase with different cellular trafficking and apparent differences in Zn2+ dependence. First, we show that both S-SMase and L-SMase, which contain several highly conserved zinc-binding motifs, are directly activated by zinc. In addition, SMase assayed from a lysosome-rich fraction of Chinese hamster ovary cells was found to be partially zinc-dependent, suggesting that intact lysosomes from these cells contain subsaturating levels of Zn2+. Analysis of Asn-linked oligosaccharides and of N-terminal amino acid sequence indicated that S-SMase arises by trafficking through the Golgi secretory pathway, not by cellular release of L-SMase during trafficking to lysosomes or after delivery to lysosomes. Most importantly, when Zn2+-dependent S-SMase was incubated with SMase-negative cells, the enzyme was internalized, trafficked to lysosomes, and became zinc-independent. We conclude that L-SMase is exposed to cellular Zn2+ during trafficking to lysosomes, in lysosomes, and/or during cell homogenization. In contrast, the pathway targeting S-SMase to secretion appears to be relatively sequestered from cellular pools of Zn2+; thus S-SMase requires exogeneous Zn2+ for full activity. This model provides important information for understanding the enzymology and regulation of L- and S-SMase and for exploring possible roles of ASM gene products in cell signaling and atherogenesis.     

Disaster-readiness of medical facilities in Aichi Prefecture

One month following the Great Hanshin Earthquake of January 17, 1995, we conducted a survey of 173 hospitals in Aichi Prefecture to pinpoint problems related to their actual disaster-readiness and the medical backup systems in place to deal with such disasters. This study revealed that staff at 50% of the surveyed hospitals could reach the hospital within an hour, but that communication is almost entirely dependent on phone lines, suggesting that cordless/portable/mobile phones, radio systems, Internet, communications satellites and the like should be studied in the days to come for possible use as effective communication alternatives in times of disaster. Whereas 92% of the surveyed hospitals had manuals dealing with fire outbreaks, other areas were less well represented. For example, only 36.9% of surveyed hospitals had manuals for earthquakes, 31.7% had manuals for power outages and 14.2% had manuals to deal with flooding and water disasters. New manuals must be developed incorporating the key points garnered from experience (especially Hanshin) and be ready for use immediately. It is the time for each hospital to seriously rethink the measures it should take to deal with disasters.     

Enantioselective antiplatelet actions of nipecotamides

This investigation retrospectively examined changes in marital satisfaction following stroke. The relationship between such changes and other pertinent factors were also examined, including severity of aphasia, knowledge of aphasia, number of months after stroke, and length of the marriage. The subjects were 40 spouses of patients with aphasia grouped according to severity of the aphasia (mild, moderate, severe). Spouses completed two different measures of marital satisfaction--the Marital Satisfaction Scale (MSS) and the Marital Comparison Level Index (MCLI). These measures were completed in both a prestroke (retrospective reporting) and a poststroke format to allow for change to be assessed. In addition, a Knowledge of Aphasia questionnaire was completed by the normal spouses to evaluate their understanding of the disorder of aphasia. There was a significant difference between prestroke and poststroke scores on both the MSS and the MCLI, indicating a lower level of satisfaction following the stroke. The amount of change between prestroke and poststroke MSS and MCLI scores was not related to either number of months poststroke or number of years married. Although there was no relationship between changes in prestroke and poststroke scores on the MCLI and Knowledge of Aphasia scores, there was a significant correlation between changes in these scores on the MSS and Knowledge of Aphasia scores. Hence, the more knowledge spouses had regarding aphasia, the less the negative impact the stroke had on marital satisfaction, as measured by the MSS. Results are discussed in terms of the interdisciplinary treatment needs of aphasic patients and the implications for future investigations.     

Repair of extensive ionizing-radiation DNA damage at 95 degrees C in the hyperthermophilic archaeon Pyrococcus furiosus

We investigated the capacity of the hyperthermophile Pyrococcus furiosus for DNA repair by measuring survival at high levels of 60Co gamma-irradiation. The P. furiosus 2-Mb chromosome was fragmented into pieces ranging from 500 kb to shorter than 30 kb at a dose of 2,500 Gy and was fully restored upon incubation at 95 degrees C. We suggest that recombination repair could be an extremely active repair mechanism in P. furiosus and that it might be an important determinant of survival of hyperthermophiles at high temperatures.     

The strategy of edge wear prediction in CIM concept

A monitoring of tool wear in different cutting operations has been studied for many years. Special techniques have been used to detect a wear status basing upon cutting forces, acoustic emission, temperature, torque and power, vibration, noise and acceleration sensors. The adapting of a proper prediction method allows to solve problems of an automatic supervision in Computer Integrated Manufacturing systems. A task of the abrasive edge wear index prediction can be formulated as follows: disposing by the data collection of the edge wear status in a time period preceding the concerning the wear status in the successive time period embraced by the prediction method.