A model for analysis of the yield and the level of clustering of radiation-induced DNA-strand breaks in hydrated plasmids.

Although it is widely accepted that the spatial distribution of strand breaks is highly relevant to the biological consequences of radiation, the extent to which strand breaks are clustered is not usually demonstrated directly from the experimental data. To evaluate the spatial distribution of radiation-induced strand breaks, the authors have developed a model for the generation of strand breaks after irradiation. The model assumes that (1) a radiation track has a certain probability of 'hitting' a plasmid, (2) the radiation generates strand break(s) by chance within a relatively small region that could produce double-strand breaks and (3) the number of strand breaks generated within the region follows a Poisson distribution. To find out whether the model is valid, the authors compared the calculated values with the experimental data obtained by a plasmid DNA assay. Taking into account the inherent bias of the plasmid assay, the model described well the experimental results of hydrated plasmids exposed to radiation.

Studies of soft X-ray-induced Auger effect on the induction of DNA damage.

PURPOSE: To understand the characteristics of DNA damage induced by Auger effect in DNA by ultrasoft X-irradiation. In situ electron paramagnetic resonance (EPR) spectroscopy as well as biochemical analysis has been applied to examine the DNA damage induction in both viewpoints of intermediate species and final products. MATERIALS AND METHODS: Unpaired electron species induced in a calf thymus DNA film irradiated with monochromatic ultrasoft X-rays (270-580 eV) was observed using an X-band EPR spectrometer installed in a synchrotron beamline. To determine the yield of single strand break (SSB), pUC18 plasmid DNA was irradiated and then analyzed by agarose gel electrophoresis. To analyze molecular change in a single strand DNA, a new technique using DNA-denaturation-treatment has been applied to quantify multiple SSB arising in both DNA strands. RESULTS: Short-lived EPR spectra were observed during irradiation. The intensity of transient EPR spectrum shows the similar energy dependence with that of the SSB yield around oxygen K-edge in particular. The fraction of the single-strand plasmid DNA (SS-DNA) after irradiation could be determined using a low-temperature-denaturation condition. The obtained slope of the dose-response for SS-DNA shows half of that of closed circular DNA as expected under the diluted solution condition. CONCLUSION: The availability of an EPR apparatus installed in a synchrotron beamline is demonstrated by detecting very short-lived unpaired electron species. Transient EPR spectra of DNA show the similar energy dependence to that of the SSB yield. The proposed DNA-denaturation assay works as expected using the low-temperature-denaturation condition.

Yields of strand breaks and base lesions induced by soft X-rays in plasmid DNA.

The yields of soft-X-ray-induced DNA damages have been measured by using closed-circular plasmid DNA. Several DNA solutions with three kinds of radical scavenger capacity and also fully hydrated DNA samples were irradiated to compare the contribution by indirect reaction of diffusible water radicals, such as OH*, with those by direct action of secondary electrons. The yields of prompt single- (SSBs) and double-strand breaks (DSBs) decrease with increasing scavenging capacity. The SSB yields for soft X-rays are approximately midway those between gamma-ray and ultrasoft X-ray data previously reported. Heat labile sites are observed only in the low scavenger condition. The yields of the base lesions revealed by post irradiation treatment with base excision repair enzymes showed a similar value for Nth and Fpg protein except in the hydrated sample. These results indicate that the direct effect of soft X-rays induces the damages with different efficiency from those by indirect effect.

A concise enantioselective synthesis of antimalarial febrifugine alkaloids.

Reaction of (S)-2-(tert-butyldiphenylsilyloxy)-5-(mesyloxy)pentanal with hydroxylamine in allyl alcohol brought about simultaneous 1,3-dipolar cycloaddition of the resulting nitrone to allyl alcohol to give three diastereoisomeric adducts, from which (+)-febrifugine and (+)-isofebrifugine, potent antimalarial alkaloids, were synthesized.

[A survey on urinary incontinence in the institutionalized elderly].

A survey on urinary incontinence in 161 (41 male, 120 female) institutionalized elderly was independently performed by urologists and attending nurses. Urinary incontinence was found in 107 cases (66%), with 76 cases (47%) suffering from severe leakage (more than 5 times a day and needs diaper). The prevalences of incontinence and severe leakage were 63% and 52% at geriatric hospitals, 59% and 29% at intermediate care centers and 78% and 63% at nursing homes, respectively. The risk factors for incontinence were consciousness disturbance, urinary urgency, impaired mobility and dementia, and those for severe leakage were apathy, loss of urinary sensation, dementia and impaired mobility. The type of incontinence was considered functional one in 81% of cases. The agreement of the incontinence type evaluated by urologists and that by nurses was found in 90% of incontinent cases. Incontinence was estimated "incurable" in 54% of cases by attending nurses. These observations indicate a high prevalence of severe and "incurable" incontinence in the institutionalized elderly, urgently warranting an effective remedy for the increasing aged society.

[The relationship between the physical features and medications in Reye-like syndrome in elderly patients].

With the increase in the aged population, it is expected that the number of debilitated aged people will increase and that the number of patients receiving many medications will increase. However, there have been few reports of clinical pharmacological studies on blood pharmacokinetics, metabolism, adverse effects, etc, of drugs used in debilitated aged people who have lowered physical and mental functions complicated by many diseases. Thus, for the large part, pharmacokinetics in these patients remains unelucidated. We experienced eight cases of marked hypoglycemia of unknown cause in patients who had not taken any hypoglycemic drugs or insulin and examined the relationships between the event and the physical features and medications of the patients. The eight patients included both males and females aged 66 to 88 years (mean: 78.5 years). The eight patients were all aged and showed cerebral infarction, reduced volition, etc. The onset of hypoglycemia was preceded by decreased appetite and an abrupt manifestation of severely disturbed consciousness a few days previously. Laboratory tests revealed marked hypoglycemia in 8 cases, leucocytosis in 7 cases (not examined in one case), metabolic acidosis in 3 cases, elevated GOT in 5 cases, elevated GPT in 2 cases, increased BUN in 1 case, and positive CRP in 4 cases. The patients had been taking an agent to activate brain metabolism/improve mental symptoms (Hopantene calcium: 7 cases; Idebenone: 1 case). The Idebenone-treated patient had received Hopantene calcium for eleven months prior to receiving Idebenone. Furthermore, the findings resembled those of Reye's syndrome often noted in children.(ABSTRACT TRUNCATED AT 250 WORDS)