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Influence of chemotherapy administration on monocyte activation by liposomal muramyl tripeptide phosphatidylethanolamine in children with osteosarcoma.

The purpose of these studies was to determine whether chemotherapy interfered with the ability of peripheral blood monocytes from patients with osteosarcoma to respond to the liposome-encapsulated activating agent muramyl tripeptide phosphatidylethanolamine (L-MTP-PE). This was done in preparation of designing an adjuvant therapy protocol that includes L-MTP-PE combined with chemotherapy postoperatively for the treatment of primary osteosarcoma. The majority of patients who fail current adjuvant chemotherapy do so while on chemotherapy. Therefore, we believe it is important to combine L-MTP-PE with chemotherapy early in the treatment course rather than waiting until all chemotherapy cycles are completed. The tumoricidal properties of monocytes from patients with osteosarcoma could be activated by L-MTP-PE to levels equal to or greater than those expressed by normal control monocytes. No intrinsic monocyte defect could be demonstrated. Single-agent chemotherapy consisting of cisplatin (CPD), high-dose methotrexate (MTX), Cytoxan (CTX, cyclophosphamide; Bristol-Myers Co, Evansville, IN), or Adriamycin (ADR, doxorubicin; Adria Laboratories, Columbus, OH) did not interfere with this activation process. There was even a suggestion of enhanced activation potential following the administration of ADR. However, when both ADR and CTX were administered together on the same day, profound suppression in monocyte activation was observed. This suppressed function returned to normal by 3 weeks postcombination therapy. We therefore conclude that L-MTP-PE can be combined with ADR, CPD, MTX, or CTX as single agents but recommend that ADR plus L-MTP-PE is the most effective combination. By contrast, we discourage the use of L-MTP-PE when ADR and CTX are given together.

Acetylmuramyl-Alanyl-Isoglutamine↗

Circadian fluctuations of contrast sensitivity in Parkinson's disease.

Spontaneous circadian fluctuations of motor symptoms in Parkinson's disease (PD) often occur, with dysfunction typically less severe in the early morning than in the afternoon. In 23 PD patients with or without a history of circadian motor fluctuations, we studied contrast sensitivity (CS), a non-motor function, considered to be dependent on dopaminergic transmission to see if it exhibits similar circadian variability. We tested CS throughout the day at 2-hour intervals beginning at 8:30 AM. To facilitate multiple testing sessions, we used a rapid, printed, forced choice test of CS not requiring a motor response. We tested CS in 43 eyes in the PD patients and 23 eyes in 12 controls at spatial frequencies of 1.5, 3, 6, 12, and 18 cycles per degree (cpd). At 8:30 AM, CS in PD did not differ from that of controls, but at all other testing times it was significantly worse at 3 or more spatial frequencies. In PD, CS was significantly worse at 2:30 PM than at 8:30 AM at 3 and 6 cpd, but in controls it was unchanged throughout the day. Separate analysis of CS in PD patients, with and without a history of circadian change in motor symptoms, revealed no significant difference between the groups. These results suggest that in PD a non-motor dopaminergic function can exhibit circadian variability and that this pattern can exist in the absence of similar variability in motor symptoms. Circadian variability which parallels the most common pattern of motor variability in PD supports the notion that the CS abnormality in this condition is related to dopamine deficiency.

Aged↗

Loss of P retinal ganglion cell function in resolved optic neuritis.

To determine the relative loss of P and M (X and Y) ganglion cell function in unilateral resolved optic neuritis, 10 patients with 20/20 or better Snellen acuity in both eyes had contrast sensitivity testing, color vision testing, and automated perimetry. We used contrast sensitivity gratings of 0.5 cycles per degree (cpd) with a rate of counterphase temporal modulation of 30 Hz and gratings of 11.4 cpd at 1 Hz. On 1 trial, patients responded when they detected the pattern of the grating and on the next trial when they 1st perceived movement. There was a significant difference in the 1 Hz high spatial frequency pattern and movement results suggesting loss of P cell function. Two patients were unable to perceive any movement with their involved eye with this target, but could detect the pattern. There was no significant difference between the involved and uninvolved eyes in the low spatial frequency pattern detection values. This is a function ascribed to the M cell. There was also loss of low spatial frequency movement detection. Although there was significant depression of the entire visual field in the involved eye, the probability plots showed the most significant loss in the cecocentral area. Farnsworth-Munsell 100 Hue color testing was also abnormal. Greater involvement of P than M ganglion cell axons may explain these contrast sensitivity abnormalities, central scotomata, and color vision loss.

Evoked Potentials, Visual↗

Spatial frequency evoked visuograms in multiple sclerosis.

We obtained steady-state visual evoked potentials (VEPs) to sinusoidal gratings alternating at 4 Hz with spatial frequencies varying from 0.5 to 8 cpd in 21 normal controls and 21 patients with multiple sclerosis (MS), and analyzed responses by fast Fourier transform. Amplitude- and phase-spatial frequency functions were obtained and referred to as amplitude and phase "visuograms." We observed two types of abnormalities in the phase visuograms of MS patients: (1) abnormal responses at all spatial frequencies tested (37%), and (2) abnormal responses only at selective spatial frequencies (52%). Some patients had phase lag limited to low, middle, or high spatial frequencies. Steady-state and transient VEPs to 2 and 4 cpd showed a similar percent of abnormalities. The use of more than one spatial frequency stimulus increased the diagnostic yield by 17%. Our data confirm that MS may selectively affect specific neuronal channels within the visual pathways.

Adolescent↗

Differentiation of fibroblast stem cells.

Primary human skin fibroblasts derived from the abdomen of 45 female donors of the four age groups 1-20, 20-40, 40-60, and 60-80 years were studied in primary explant, in primary low-density mass cultures, and in primary clonal populations in vitro. As a function of the age of the donor, primary mitotic and postmitotic fibroblasts in the three primary cell systems analysed represent heterogeneous populations with reproducible changes in the proportions of the mitotic fibroblasts MF I, MF II, MF III, and postmitotic fibroblasts PMF IV, PMF V, PMF VI, and PMF VII. These findings make it very likely that equivalent cell types exist in the connective tissue of skin in vivo, and that these cells undergo reproducible changes in the proportions of the mitotic and postmitotic counterparts in vivo as a function of the age of the donor. Secondary mitotic human skin fibroblast populations of the cell line HH-8 in vitro underwent 53.6 +/- 6.0 cumulative population doublings (CPD) in 302 +/- 27 days. If appropriate methods are applied, mitotic fibroblasts differentiate spontaneously into postmitotic fibroblasts which are kept in stationary cultures for up to 305 +/- 41 additional days. As a function of the CPD level and of the duration of stationary culture, secondary mitotic and postmitotic fibroblast populations are heterogeneous populations with reproducible changes in the proportions of mitotic fibroblasts MF I, MF II, and MF III, and postmitotic fibroblasts PMF IV, PMF V, PMF VI, and PMF VII. The seven secondary fibroblast cell types show differentiation-dependent and cell-type specific patterns of [35S]methionine polypeptides in total soluble cytoplasmic and nuclear proteins, in secreted proteins, and in membrane bound proteins. These findings make it very likely that the morphologically recognizable primary and secondary fibroblasts differentiate spontaneously along a seven stage terminal cell lineage MF I - MF II - MF III - PMF IV - PMF V - PMF VI - PMF VII in three compartments of the fibroblasts stem cell system.

Adolescent↗

DNA photorepair in echinoid embryos: effects of temperature on repair rate in Antarctic and non-Antarctic species.

To determine if an Antarctic species repairs DNA at rates equivalent to warmer water equivalents, we examined repair of UV-damaged DNA in echinoid embryos and larvae. DNA repair by photoreactivation was compared in three species Sterechinus neumayeri (Antarctica), Evechinus chloroticus (New Zealand) and Diadema setosum (Tropical Australia) spanning a latitudinal gradient from polar (77.86 degrees S) to tropical (19.25 degrees S) environments. We compared rates of photoreactivation as a function of ambient and experimental temperature in all three species, and rates of photoreactivation as a function of embryonic developmental stage in Sterechinus. DNA damage was quantified from cyclobutane pyrimidine dimer (CPD) concentrations and rates of abnormal embryonic development. This study established that in the three species and in three developmental stages of Sterechinus, photoreactivation was the primary means of removing CPDs, was effective in repairing all CPDs in less than 24 h, and promoted significantly higher rates of normal development in UV-exposed embryos. CPD photorepair rate constant (k) in echinoid embryos ranged from 0.33 to 1.25 h(-1), equating to a time to 50% repair of between 0.6 and 2.1 h and time to 90%repair between 3.6 and 13.6 h. We observed that experimental temperature influenced photoreactivation rate. In Diadema plutei, the photoreactivation rate constant increased from k=0.58 h(-1) to 1.25 h(-1), with a Q(10)=2.15 between 22 degrees C and 32 degrees C. When compared among the three species across experimental temperatures (-1.9 to 32 degrees C), photoreactivation rates vary with a Q(10)=1.39. Photoreactivation rates were examined in three developmental stages of Sterechinus embryos, and while not significantly different, repair rates tended to be higher in the younger blastula and gastrula stages compared with later stage embryos. We concluded that photoreactivation is active in the Antarctic Sterechinus, but at a significantly slower (non-temperature compensated) rate. The low level of temperature compensation in photoreactivation may be one explanation for the relatively high sensitivity of Antarctic embryos to UV-R in comparison with non-Antarctic equivalents.

Animals↗

Non-consultant career grade doctors in genitourinary medicine: as revalidation approaches, are some jobs at risk?

The Genitourinary Medicine Non-Consultant Career Grade Group (GUM NCCG Group) was established for the purpose of looking at training and contractual issues for this heterogeneous group of doctors. In June 2003, 700 questionnaires were posted to NCCG doctors in the UK to enquire about various aspects of working conditions. A summary of the 244 replies (35% response) is presented. Eighty-four (34%) had a job plan and 81 (33%) had had an appraisal. Just over one-third (38%) had time allocated for continuing medical education (CME), audit and administration. The response of employers to attempts by NCCGs to upgrade was poor. In all, 195 (80%) said they were registered for the purpose of continuing professional development (CPD), 43 (18%) were not and six people did not know whether they were registered or not. These results give cause for real concern at this point regarding revalidation pathways. Our survey highlights that NCCGs are disadvantaged in terms of appraisal, CPD and career progression and some jobs will be at risk as revalidation approaches.

Accreditation↗

Relationship between ultraviolet-B sensitivity and cyclobutane pyrimidine dimer photorepair in rice.

Among Indica rice cultivars (Oryza sativa L. cvs.) that belong to the aus ecotype from the tropical Bengal region, where the amount of ultraviolet-B (UV-B) radiation in the solar radiation is relatively great, Marich-bati cultivar has exhibited resistance to UV-B radiation, while Surjamkhi cultivar appeared to be less resistant. We have examined the susceptibility to cyclobutane pyrimidine dimer (CPD) induction by UV-B radiation and the ability to photorepair CPDs using these two cultivars. UV-B radiation produced similar dimer levels in the leaves of the two cultivars. In contrast, the ability to photorepair CPDs in the UV-sensitive Surjamkhi cultivar was lower than that in the UV-resistant Marich-bati cultivar. These results were similar to our previous data, namely, that a UV-sensitive Japanese rice cultivar (Oryza sativa L. cv. Norin 1) cultivated in the moderate climate of Japan is deficient in its ability to photorepair CPDs. Thus, these results suggest that a strong correlation exists between the sensitivity to UV-B and the photorepair deficiency, and that a low ability in CPD photorepair may be a principal factor in determining the UV-B sensitivity in rice plants.

DNA Repair↗

Establishment and characterization of GSA-1, a human cell line highly susceptible to apoptosis after free-fall.

The induction of apoptosis by microgravity and/or gravity-changing stress is considered to be one of the important causes of cell death, although the molecular mechanisms of the apoptotic event remain unclarified. In this study, we established a cell line, GSA-1, from ethyl methanesulfonate-treated human RSa cells. GSA-1 cells were highly susceptible to apoptosis after a free-fall; 24.4% of these cells underwent apoptosis after free-fall, compared with only 6% of the RSa cells. The apoptosis of GSA-1 cells was augmented by ultraviolet (UV, principally 254-nm wavelength) irradiation before free-fall to a greater extents than those in RSa cells. The molecular mechanisms of apoptosis included p53 and Bax proteins; the expression of nuclear p53 and cytoplasmic Bax in GSA-1 cells increased at 4 h after free-fall irrespective of irradiation. In addition, the rate of removal of cyclobutane pyrimidine dimer (CPD) in UV-irradiated GSA-1 cells was higher in cells exposed to free-fall than in those under the 1-G condition. Our results suggested that in GSA-1 cells, free-fall accelerates apoptosis, and that this process is associated with the accumulation of p53 and Bax, as well as CPD removal. Thus, GSA-1 cells should be useful for investigating the mechanism of cellular response, including the induction of apoptosis under gravity-changing stress.

Apoptosis↗

Observations on the biochemical effects of transfusion of citrate-phosphate-dextrose stored blood in man.

Preliminary data on the biochemical effects of the transfusion of three units of CPD blood in man is presented. Free (ionized) calcium was found to decrease approximately two minutes following initiation of the transfusion of CPD stored blood at a rate of 50 ml/min. Due to mixing problems, arterial and not venous specimens were found necessary to monitor accurately the severity of these decreases. Parathyroid hormone in the peripheral blood was found to increase two to four minutes after the initiation of transfusion. Decreases in blood pressure were observed during transfusion. The blood pressure recovered when the transfusion was stopped and did not decrease any further after restarting the transfusion, were found out not to increase or decrease consistently, and only modest changes in plasma potassium were observed.

Aged↗

Perimetry of contrast detection thresholds of moving spatial sine wave patterns. I. The near peripheral visual field (eccentricity 0 degrees-8 degrees).

Contrast detection thresholds for moving spatial sine wave gratings were obtained, at the fovea, and at eccentricities of 1 degree, 2 degrees, 4 degrees, 6 degrees, and 8 degrees on the nasal horizontal meridan, for two subjects. The target field subtended 30 X 30 minutes of arc. The spatial frequency range extended from 2 cpd up to the spatial resolution limit, the temporal frequency range from 0.1 Hz up to the CFF. Mean retinal illuminance was 10 trolands. We find for these conditions: (i) Contrast detection thresholds are higher, the higher the spatial and/or temporal frequency of the stimulus. (ii) Acuity appears to be independent of the temporal frequency, the CFF appears to be independent of the spatial frequency. (iii) The higher the eccentricity, the higher the contrast detection threshold for any drifting sine wave pattern. The threshold doubles roughly any 2 degrees-3 degrees for spatial frequencies of 2-20 cpd, except that the visual field for a given fineness of grating is blind beyond a certain critical eccentricity. This critical eccentricity is a monotonically decreasing function of the spatial frequency of the grating. These measurements do not support the hypothesis that coarse patterns are preferentially detected at extrafoveal sites in the visual field.

Adult↗

Suppressive rod-cone interactions: evidence for separate retinal (temporal) and extraretinal (spatial) mechanisms in achromatic vision.

We investigated the influence of selective rod light and dark adaptation on cone-mediated sensitivity to monocular displays modulated sinusoidally in both spatial and temporal domains. Rod light adaptation (1) increased sensitivity to high spatial frequencies [> or = 8 cycles per degree (cpd)] flickered slowly (< or = 2 Hz), an effect that we refer to as grating suppressive rod-cone interaction (gSRCI); (2) increased sensitivity to low spatial frequencies (< or = 2 cpd) flickered rapidly (> or = 8 Hz), an effect that we refer to as flicker suppressive rod-cone interaction (fSRCI); and (3) had relatively little influence on intermediate temporal-spatial-frequency combinations. The magnitudes of both gSRCI and fSRCI increased as the retinal position of the test display was increasingly displaced parafoveally. In parafoveal retina, both forms of suppressive rod-cone interaction increased as the overall dimension of the test stimulus decreased. However, sensitivity to high spatial frequencies is equally well influenced by adaptation of the viewing and the contralateral eye, while the adapted state of the nonviewing eye negligibly influences sensitivity to rapid flicker. Moreover, gSRCI cannot be observed with a small (30-arcmin) grating restricted to the fovea, while fSRCI is a prominent effect with small foveal test stimuli. Collectively, these results and neurobiological evidence suggest that fSRCI reflects a mechanism restricted to distal retinal, while gSRCI involves extraretinal neural circuitry.

Adaptation, Ocular↗

Curvature and separation discrimination at texture boundaries.

Visual discrimination of contour curvature was investigated by using contours defined by the locus of points at which the phase of a square-wave grating was shifted by 180 degrees (a texture boundary). Curvature-increment thresholds were measured for contour curvatures from 0.31 to 10.65 deg-1, for grating spatial frequencies of 4.0 and 16.0 cycles per degree (cpd), and for gratings in either sine or cosine phase at the point of maximum curvature. Thresholds for these conditions were compared with curvature discrimination at black-white edges. Grating phase had no effect on performance at any curvature or grating frequency, but 16.0-cpd gratings produced a threshold elevation at all curvatures by an average factor of 2.4. Two-line separation discrimination was also measured for lines defined by texture boundaries. These data can be predicted by a model incorporating end-stopped complex cells of a type reported physiologically in primate area V2.

Form Perception↗

Bupropion for smoking cessation : predictors of successful outcome.

OBJECTIVES: To identify predictors of smoking abstinence at the end of medication use that could assist in the optimal use of a sustained-release (SR) form of bupropion for treating cigarette smokers. DESIGN: A double-blind, placebo-controlled, dose-response trial. SETTING: Multicenter (three sites) study conducted in the United States. PARTICIPANTS: Six hundred fifteen healthy men and women (> or = 18 years of age) who were smoking > or = 15 cigarettes per day and who were motivated to stop smoking. INTERVENTION: Random assignment of patients to placebo or SR bupropion treatment, 100, 150, or 300 mg/d, for 7 weeks (total duration of study was 52 weeks: 7 weeks of treatment and 45 weeks of follow-up). MEASUREMENTS AND RESULTS: Logistic regression was used to identify predictors of abstinence at the end of the medication phase. Univariate predictors included the following: bupropion dose (p < 0.001); older age (p = 0.024); lower number of cigarettes smoked per day (cpd) (p < 0.001); lower Fagerström Tolerance Questionnaire score (p = 0.011); longest time previously abstinent that was < 24 h or > 4 weeks (p < 0.001); absence of other smokers in the household (p = 0.021); greater number of previous stop attempts (p = 0.019); and study site (p = 0.004). Multivariate predictors of abstinence at the end of the medication phase were the following: higher bupropion dose (p < 0.001); lower number of cpd (p < 0.001); longest time previously abstinent from smoking (p = 0.002); male gender (p = 0.014); and study site (p = 0.021). CONCLUSION: Bupropion SR therapy was effective in treating cigarette smokers independently of all other characteristics studied. Lower smoking rate, brief periods (ie, < 24 h) or long periods (ie, > 4 weeks) of abstinence with previous attempts to stop smoking, and male gender were predictive of better outcomes, independent of the dose of bupropion that was used.

Adult↗

Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism.

Major pulmonary embolism (PE) results whenever the combination of embolism size and underlying cardiopulmonary status interact to produce hemodynamic instability. Physical findings and standard data crudely estimate the severity of the embolic event in patients without prior cardiopulmonary disease (CPD) but are unreliable indicators in patients with prior CPD. In either case, the presence of shock defines a threefold to sevenfold increase in mortality, with a majority of deaths occurring within 1 h of presentation. A rapid integration of historical information and physical findings with readily available laboratory data and a structured physiologic approach to diagnosis and resuscitation are necessary for optimal therapeutics in this "golden hour." Echocardiography is ideal because it is transportable, and is capable of differentiating shock states and recognizing the characteristic features of PE. Spiral CT scanning is evolving to replace angiography as a confirmatory study in this population. Thrombolytic therapy is acknowledged as the treatment of choice, with embolectomy reserved for those in whom thrombolysis is contraindicated.

Blood Gas Analysis↗

Effect of a short course of clarithromycin therapy on sputum production in patients with chronic airway hypersecretion.

STUDY OBJECTIVE: Long-term administration of macrolide antibiotics reduces sputum production in patients with chronic airway diseases, probably by inhibiting airway inflammation. The objective of the present study was to determine the acute effects of a macrolide on airway chloride secretion and sputum production. METHODS: We first investigated the effect of erythromycin treatment on chloride diffusion potential difference (CPD) across tracheal mucosa in vivo. Next, we conducted a double-blind, parallel-group study examining the effect of 7 days of treatment with clarithromycin (400 mg/d), amoxicillin (1,500 mg/d), or cefaclor (750 mg/d) in patients with chronic bronchitis or bronchiectasis without apparent respiratory infection. RESULTS: IV administration of erythromycin decreased the CPD of rabbit tracheal mucosa in a dose-dependent manner. Treatment of patients with clarithromycin decreased sputum production, whereas amoxicillin and cefaclor treatment had no effect. The percentage of patients whose sputum decreased > 30% from baseline (responders) was 38% in the clarithromycin group, 7% in the amoxicillin group, and 0% in the cefaclor group. During treatment with clarithromycin, the sputum solid composition increased and chloride concentration decreased in responders, but these changes were not observed in nonresponders. CONCLUSION: Short-term administration of 14-membered macrolide reduces chronic airway hypersecretion, presumably by inhibiting chloride secretion and the resultant water secretion across the airway mucosa.

Adult↗

Diagnosis of airflow limitation combined with smoking cessation advice increases stop-smoking rate.

OBJECTIVES: To assess how the diagnosis of airflow limitation (AL) combined with advice to stop smoking in middle-aged smokers influence the smoking cessation rate and to identify predictors of successful outcome. DESIGN: Prospective, single-center, comparative study of the effects of smoking intervention in smokers with diagnosed AL and in smokers with normal lung function (NLF). SETTING: University hospital, out-patient clinic. PARTICIPANTS: Of 659 smokers participating in a population spirometric screening for COPD combined with smoking cessation advice, 558 (AL, 297 smokers; NLF, 261 smokers) were invited for a follow-up after 1 year. INTERVENTION: At follow-up, spirometry was repeated and smoking status was assessed. Nonsmoking status was validated with carbon monoxide measurements in exhaled air. Patients who did not come for the follow-up visit were considered to be smokers. RESULTS: Of 558 smokers invited, 368 (66%) presented for the follow-up visit. All had tried to reduce their smoking habit. The number of cigarettes smoked per day (cpd) at 1 year was - 5.2 (p < 0.01) in patients with AL and - 2.7 (not significant [NS]) in those with NLF. The 1-year cessation rate in smokers with AL was 10.1% vs 8.4% in smokers with NLF (NS). After stratifying the patients according to AL severity, the highest cessation rate was observed in smokers with moderate and severe AL (16.5%) compared to smokers with mild AL (6.4%; p < 0.001) and smokers with NLF (8.4%; p < 0.05). In a univariate analysis, the cessation of smoking was correlated with older age (p < 0.001), later age when starting smoking (p < 0.005), lower tobacco exposure (in pack-years; p < 0.01), fewer cpd (p < 0.001), and lower lung function (p < 0.05). No interaction effect was observed for any of the studied variables using two-way analysis of variance. In a stepwise logistic regression analysis, age (p < 0.001), tobacco exposure (in pack-years; p < 0.001), and FEV(1) percent predicted (p < 0.01) proved to be significant predictors of success in stopping smoking. CONCLUSION: All smokers, irrespective of their lung function, tried to modify their habit as the result of screening for COPD combined with smoking cessation advice. The diagnosis of AL motivated smokers to attempt to quit smoking. Older age, lower tobacco exposure, and lower lung function were the predictors of success in quitting smoking.

Age Factors↗

Fluoroimaging-based immunoassay of DNA photoproducts in ultraviolet-B-irradiated tadpoles.

Sensitive and accurate measurement of photoproducts induced in DNA by natural or artificial ultraviolet-B (UVB; and UVC) light is essential to evaluate the toxic and mutagenic effects of this radiation. Monoclonal antibodies specific for the two major classes of photoproducts-cyclobutane pyrimidine dimers (CPDs) and pyrimidine-[6-4]-pyrimidinone photoproducts ([6-4]PPs)-have made possible highly specific and sensitive assays. Described here is the use of these primary antibodies with fluorescent secondary antibodies to generate 96-spot arrays. Stable fluorescence signals are rapidly and sensitively scored by fluoroimaging and computer analysis of peak-and-valley traces. CPD levels in a series of calibration standards are determined by acid hydrolysis/thin-layer chromatography analyses of radiolabeled bacterial DNA, UV-irradiated to known high fluences, and linear extrapolation to known lower fluences. The nonlinear fluorescence vs CPD curve reflects the effect of photoproduct concentration on single vs double binding by divalent antibody proteins. This technique is applied to photoproducts in whole inbred Xenopus laevis tadpoles, chronically irradiated at a series of UVB fluences that reach a lethality threshold when in vivo steady-state photoproduct levels are still quite low. As few as 0.01-0.02 CPDs per DNA kbp can be reliably detected, at signal/noise ratios of roughly 3:1.

Animals↗