Visual performance in the rhesus monkey after exposure to blue light.

Rhesus monkeys trained to perform a visual task (Landolt ring discrimination) were exposed for 1000 sec to known amounts of 441 nm light by means of a 2500 W xenon lamp with narrow bandpass filter. Radiant exposures to the macula of 30 J/cm² did not impair vision, but 60 J/cm² produced a transient loss of 20/20 vision which lasted from 20 to 30 days. A radiant exposure of 90 J/cm² produced a permanent loss of 20/20 vision. These results, in addition to explaining solar retinitis and eclipse blindness, correlate well with the retinal photopathology of the short wavelength photochemical lesion.     

Pre- and postsynaptic dopaminergic activities of U-86170F

Summary The biochemical, endocrine, receptor binding, and behavioral effects of the putative dopamine autoreceptor agonist, U-86170F, were evaluated in various in vivo and in vitro models. U-86170F and apomorphine were shown to cause a significant reversal of the effects of -butyrolactone (GBL) on dopamine accumulation in mouse striata. In contrast to apomorphine, U-86170F had a ceiling effect on the extent of the reversal of GBL effects (55%), whereas apomorphine had an 82% reversal. The effect on striatal homovanillic acid (HVA) levels was also monitored, and both compounds exerted a similar and significant reduction in striatal HVA. A comparison was made between the effects of intraperitoneal (i.p.) and oral administration of U-86170F in the -methyl-p-tyrosine (-MPT)/prolactin model in rats. When administered by the i.p. route, U-86170F suppressed the effects of -MPT on prolactin level increase, having an ED₅₀ of about 0.03 mg/kg, and when administered by the oral route, its ED₅₀ was approximately 0.1 mg/kg. U-86170F has been shown to be a potent dopamine autoreceptor agonist in the GBL, prolactin, and HVA models, with an effective i.p. dose of approximately 0.03 mg/kg. When evaluated for postsynaptic dopaminergic activity in the reserpinized mouse model, and compared to apomorphine, U-86170F was found to increase locomotor activity, but its maximum effect was only 65% of that attained with apomorphine. Higher doses were needed for postsynaptic effects.In receptor binding studies using cloned D2 receptor preparations, U-86170F was found to exhibit agonist binding properties similar to dopamine as demonstrated by their inhibition of 3H-raclopride binding. Both compounds exhibited biphasic inhibition curves, with U-86170F having K_i values of 7.5 nM and 250 nM, and for dopamine the K_i values were 34.7 nM and 1031 nM. Binding studies conducted in the presence of GTP yielded only one site with Kis of 289 nM and 670 nM, for both U-86170F and dopamine, respectively.The results presented in this report demonstrated that U-86170F is a potent dopamine autoreceptor agonist, with limited activity at the postsynaptic receptor. Send offprint requests to R.A. Lahti at the above address     

Temperature and the energy cost of oscillatory work in teleost fast muscle fibres

Bundles of 20–30 fast muscle fibres were isolated from the abdominal myotomes of the short-horned sculpin (Myoxocephalus scorpius L.). The energy cost of contraction was measured during oscillatory work at 4 °C and 15 °C following treatment with iodoacetate and nitrogen gas to block glycolysis and aerobic metabolism. Isolated fibres were subjected to sinusoidal length changes about in situ resting length and stimulated at a selected phase in the strain cycle. Preliminary experiments with untreated preparations established the strain amplitude and stimulation parameters required to maximize work output over a range of cycle frequencies at 4 °C and 15 °C. Following oscillatory work, treated preparations were rapidly frozen, freeze-dried and the concentrations of phosphocreatine (PCr), creatine, adenosine 5-triphosphate (ATP), adenosine 5- di- and mono-phosphate and inosine 5-monophosphate measured by high performance liquid chromatography. The concentration of PCr declined in proportion to the total work done for up to 64 cycles without a significant change in ATP. Maximum power output was produced at a cycle frequency of 5 Hz at 4 °C (14–18 W/kg) and 17 Hz at 15 °C (23–27 W/kg). The rate of utilization of PCr per cycle was independent of temperature. However, since work per cycle was higher at 4 °C (2.7–3.7 mJ/g wet weight) than 15 °C (1.2–1.6 mJ/g wet weight), the energetic cost of contraction decreased with increasing temperature.     

Quantitative fluorescence image analysis of deoxyribonucleic acid ploidy in urine from normal children

Quantitative fluorescence image analysis incorporates the 2 diagnostic techniques of cytological analysis with quantitation of deoxyribonucleic acid (DNA). Exfoliated urinary cells are ideal for analysis by this method, which allows the identification of "rare event" abnormal cells. We evaluated the urine from 50 children who had undergone cystoscopy or were catheterized for other reasons. The urine was free of infection by urinalysis. Cytological analysis demonstrated normal or atypical cells in all patients. Of the patients 1 (2%) had greater than 2 of 500 cells analyzed with greater than 5C DNA and 4 (8%) had greater than 2 of 500 cells with greater than 5C double stranded nucleic acid. These data suggest that it may be "normal" for urine to contain "rare event" abnormal cells. The significance of this finding is unclear at present.     

Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors.

PURPOSE: Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial. EXPERIMENTAL DESIGN: We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count > or = 5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (> or = 5 cm; OR = 4.2). CONCLUSIONS: The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs.