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At least 613 records · Page 34Linked to original sources
PubMed2006

BRCA1 promotes induction of ssDNA by ionizing radiation.

The BRCA1 tumor suppressor contributes to the repair of DNA double-strand breaks (DSB) through homologous recombination, but the mechanism is unknown. The rapid accumulation of BRCA1 into nuclear foci in response to induction of DNA breaks suggests that BRCA1 may function in an early step in the repair pathway. We examined the role of BRCA1 in one such early step, the resection of DSBs to generate ssDNA. The appearance of ssDNA in response to ionizing radiation is similar to that of BRCA1 foci formation, suggesting that the two processes are related. Furthermore, BRCA1 colocalizes to ssDNA sites induced by ionizing radiation. Overexpression of BRCA1 causes an increase in cells exhibiting ssDNA induced by ionizing radiation. Mutant BRCA1 that lacks the COOH-terminal BRCT domain also promotes ssDNA but fails to form nuclear foci. Knockdown of BRCA1 expression reduces ssDNA and Rad51 foci formation in response to ionizing radiation. These results indicate that BRCA1 promotes induction of ssDNA in response to ionizing radiation and accumulates at sites of ssDNA.

BRCA1 Protein↗
PubMed2001

Decreased levels of ionized calcium one year after hemithyroidectomy: importance of reduced thyroid hormones.

BACKGROUND: Previously we have found reduced levels of total serum calcium and 1,25(OH)2D3 despite an unaltered stimulated parathyroid hormone (PTH) secretion 1 year after hemithyroidectomy. The present study was undertaken to elucidate the possible relationship between calcium homeostasis, thyroid hormones and bone resorption in a group of 45 consecutive patients subjected to hemithyroidectomy because of a solitary nodule. All patients had free T4 and T3 levels within normal range preoperatively. METHODS: Thyroid hormones, bone mineral and biochemical variables known to reflect calcium homeostasis were studied. Patients were divided into three separate groups depending on their pre- and postoperative thyroid hormone status. RESULTS: One year postoperatively, serum levels of free T4 were decreased and that of thyrotropin (TSH) increased in the entire group of patients. The concentration of ionized calcium was reduced from 1.25 +/- 0.05 to 1.22 +/- 0.04 (p < 0.001) despite an unaltered PTH value (2.8 +/- 1.0 vs. 3.1 +/- 1.5, p = 0.50). A significant reduction in C-terminal telopeptide type 1 collagen (1CTP) indicated decreased bone resorption 1 year after surgery (p < 0.05). Subgroup analysis showed that a reduction in ionized calcium was seen only among patients with a postoperative decrease in free T4. Patients with subclinical hyperthyroidism preoperatively presented the lowest postoperative levels of ionized calcium, significantly reduced levels of 1CTP and increased levels of phosphate and creatinine. Multiple linear regression analysis showed that age (p < 0.05) and postoperatively changed serum levels of TSH (p < 0.05), creatinine (p < 0.05), phosphate (p < 0.001) and FT4 (p < 0.01) were independently associated with altered levels of ionized calcium. CONCLUSION: We conclude that the reduction in ionized calcium 1 year after hemithyroidectomy was not due to PTH deficiency. Instead our results suggest that the reduced effects of thyroid hormones on bone and kidney function is essential.

Adult↗
PubMed1987

Serum ionized calcium--a predictor of therapeutic response to slow calcium channel blockade in essential hypertension.

In 20 patients with mild to moderate essential hypertension, serum ionized calcium was determined before and after four weeks of treatment with 240 mg verapamil sustained release bid. Pretreatment systolic blood pressure was inversely correlated to serum ionized calcium (r = -0.44, p = 0.05). Mean blood pressure was significantly (p less than 0.001) reduced (from 161/100 to 145/88 mm Hg), but mean serum ionized calcium did not change during treatment (from 1.23 to 1.24 mmol/L). A significant inverse correlation (r = -0.56, p = 0.01) was found between pretreatment serum ionized calcium and reduction in systolic blood pressure during verapamil treatment. Thus serum ionized calcium in untreated essential hypertensive patients may predict the blood pressure response to the slow calcium channel blocker verapamil.

Adult↗
PubMed1992

Dependence of measured ionized calcium on protein concentration as measured by three ion-selective electrodes.

A positive effect of protein on the measurement of ionized calcium in serum by ion-selective electrodes (ISEs) has been previously reported and the present study confirms this finding. Ionized calcium in serum was measured in the presence of increasing protein concentrations induced by venous stasis in 17 healthy volunteer subjects. Ionized calcium was measured using two commercial analysers, a Radiometer ICA2 analyser and a Baker Analyte+2 analyser, and a calcium cell devised by Covington for the calcium reference method (CRM). Both commercial analysers used charged ionophores and the CRM used a neutral carrier ionophore in the selective membrane. A small but significant rise in ionized calcium with increasing protein was measured on all analysers. Substitution of isotonic KCl for saturated KCl in the reference electrode of the CRM resulted in significantly reduced values for ionized calcium in paired serum samples when measured using the isotonic salt bridge. This study supports the premise that the positive effect of protein is related to the salt bridge concentration of the reference electrode rather than the ISE membrane composition.

Adult↗
PubMed1985

Cutaneous carcinomas and soft tissue sarcomas induced by ionizing radiation therapy. Presentation of a series of 42 cases.

Forty-two cases of tumors of the skin and of the soft tissues immediately beneath the skin, presumably induced by ionizing radiotherapy, are reported: 35 were carcinomas, 2 angiosarcomas, 2 leiomyosarcomas of the dermis and 3 fibrosarcomas. In 31 of the 35 cases of carcinomas, multiple neoplastic foci were found in the skin area exposed to the ionizing radiation. The median age of the patients at the time of exposure to ionizing radiation was 32.5 years for those with carcinomas and 30 years for the others. The relatively young age at exposure to the ionizing radiation may have influenced onset of the tumor. The median interval between exposure to ionizing radiation and clinical finding of the tumor was 18.1 years for the carcinomas and 16 for the other tumor types. The radiation dose to which the patients had been subjected varied for the carcinomas from 12 to 25 Gy and for the other tumors from 40 to 50 Gy, administered over 1 to 4 years in the cases of carcinomas and 4 to 5 weeks in the other cases. The dose administered to the cases with cutaneous carcinomas was rather low, since almost all these patients had benign disease; however, it is in this dose range (12-25 Gy) that, according to Gray, a relatively high incidence of induced tumors is verified. In the opinion of the author of the present paper, the multiplicity of neoplastic carcinomatous foci in the skin area exposed to radiation confirms Gray's hypothesis; also, the time over which the dose was administered was presumably important in determining such multiplicity. The soft tissue sarcomas occurred only in patients previously subjected to radiotherapy, according to traditional modalities, for malignant neoplasms. The carcinomas were observed almost always in the trunk, and like spontaneous carcinomas at this site they were almost exclusively of basal cell type.

Adult↗
PubMed2006

Clinical and cellular ionizing radiation sensitivity in a patient with xeroderma pigmentosum.

XP14BR is a cell line derived from a xeroderma pigmentosum (XP) patient from complementation group C. The patient was unusual in presenting with an angiosarcoma of the scalp, treated by surgical excision and radiotherapy. Following 38 Gy in 19 fractions with 6 MEV electrons, a severe desquamation and necrosis of the underlying bone ensued, and death followed 4 years later. The cell line was correspondingly hypersensitive to the lethal effects of gamma irradiation. We had previously shown that this sensitivity could be discriminated from that seen in ataxia-telangiectasia (A-T). The cellular response to ultraviolet radiation below 280 nm (UVC) was characteristic of XP cells, indicating the second instance, in our experience, of dual cellular UVC and ionizing radiation hypersensitivity in XP. We then set out to evaluate any defects in repair of ionizing radiation damage and to verify any direct contribution of the XPC gene. The cells were defective in repair of a fraction of double strand breaks, with a pattern reminiscent of A-T. The cell line was immortalized with the vector pSV3neo and the XPC cDNA transfected in to correct the defect. The progeny derived from this transfection showed the presence of the XPC gene product, as measured by immunoblotting. A considerable restoration of normal UVC, but not ionizing radiation, sensitivity was observed amongst the clones. This differential correction of cellular sensitivity is strong evidence for the presence of a defective radiosensitivity gene, distinct from XPC, which is responsible for the clinical hypersensitivity to ionizing radiation. It is important to resolve how widespread ionizing radiation sensitivity is amongst XP patients.

Cell Death↗
PubMed2000

IFCC recommended reference method for the determination of the substance concentration of ionized calcium in undiluted serum, plasma or whole blood.

A reference method is described for the determination of the substance concentration of ionized calcium in plasma by which ionized calcium (free or unbound) may be reliably determined on the basis of calibration with aqueous solutions with known concentration of ionized calcium. The composition of the calibration solutions is chosen such that the activity coefficient of the calcium ion is assumed to be identical both in the calibration solutions and in "normal" plasma, i.e. by convention, the ionic strength (Im) is 0.160 mol/kg. The convention is adopted of reporting ionized calcium measurements as concentration expressed as mmol/l. The proposed reference method for ionized calcium measurement in plasma is based on the use of a cell consisting of an external reference electrode with a saturated potassium chloride liquid/liquid junction in combination with a calcium ion-selective membrane electrode of defined construction and performance. Procedures for using the reference cell and a protocol for sample measurement are described. The preparation of the calibration solutions to be used are described in detail in Appendix A, secondary calibration solutions and check standards in Appendix B, and reference cell vessel design in Appendix C.

Blood↗
PubMed2001

Annual rhythmic and non-rhythmic biological variation of magnesium and ionized calcium concentrations.

The annual inter- and intra-individual biological variation, including the circannual rhythmic variation, of the serum concentrations of magnesium and ionized calcium has been investigated in a group of 51 apparently healthy volunteers. Venous blood specimens were collected on intervals of once a month within a one-year period, using a standardized protocol. The inter-individual coefficients of variation were 5.12% for magnesium and 1.58% for ionized calcium. The medians of the intra-individual coefficients of variation were 1.93% for magnesium and 2.18% for ionized calcium. These data were used to determine the allowable imprecision, the allowable systematic error, the critical difference for significant change detection, and the usefulness of population reference values (index of individuality). Of the quantities studied, only the serum concentration of ionized calcium shows a significant annual rhythmic variation (amplitude 1.3%), although this result may be due to the between-run metrological variance, considering that the concentration of ionized calcium of the control material used during the study possesses a similar significant rhythmic variation.

Adult↗
PubMed2005

pH dependence of amide chemical shifts in natively disordered polypeptides detects medium-range interactions with ionizable residues.

A growing number of natively disordered proteins undergo a folding/binding process that is essential for their biological function. An interesting question is whether these proteins have incompletely solvated regions that drive the folding/binding process. Although the presence of predominantly hydrophobic buried regions can be easily ascertained by high-sensitivity differential scanning calorimetry analysis, the identification of those residues implicated in the burial requires NMR analysis. We have selected a partially solvated natively disordered fragment of Escherichia coli, thioredoxin, C37 (38-108), for full NMR spectral assignment. The secondary chemical shifts, temperature coefficients, and relaxation rates (R(1) and R(2)) of this fragment indicate the presence of a flexible backbone without a stable hydrogen bond network near neutral pH. (1)H-(15)N heteronuclear single quantum coherence analysis of the pH dependence of amide chemical shifts in fragment C37 within pH 2.0 and 7.0 suggests the presence of interactions between nonionizable residues and the carboxylate groups of four Asp and four Glu residues. The pH midpoints (pH(m)) of the amides in the ionizable residues (Asp or Glu) and, consequently, the shifts in the pH(m) (DeltapH(m)) of these residues with respect to model tetrapeptides, are sequence-dependent; and the nonionizable residues that show pH dependence cluster around the ionizable ones. The same pH dependence has been observed in two fragments: M37 (38-73) and C73 (74-108), ruling out the participation of long-range interactions. Our studies indicate the presence of a 15-residue pH-dependent segment with the highest density of ionizable sites in the disordered ensembles of fragments C37 and M37. The observed correlations between ionizable and nonionizable residues in this segment suggest the organization of the backbone and side chains through local and medium-range interactions up to nine residues apart, in contrast to only a few interactions in fragment C73. These results agree qualitatively with the predominantly hydrophobic buried surface detected only in fragments C37 and M37 by highly sensitive differential scanning calorimetry analysis. This work offers a sensitive and rapid new tool to obtain clues about local and nonlocal interactions between ionizable and nonionizable residues in the growing family of natively disordered small proteins with full NMR assignments.

Amides↗
PubMed2005

Melanoma and ionizing radiation: is there a causal relationship?

This review was initiated in response to concerns that ionizing radiation could be a cause of melanoma. Studies presenting the relative risks for melanoma after external ionizing radiation exposure were in seven categories: (1) The Canadian Radiation Dose Registry, (2) nuclear industry workers, (3) subjects near nuclear test blasts, (4) survivors of the atomic bombings of Japan, (5) airline pilots and cabin attendants, (6) recipients of medical radiation, and (7) radiological technicians. Relative risks for leukemia in each of the studies were used to confirm the likelihood of exposure to ionizing radiation. When studies within a category were compatible, meta-analytic methods were used to obtain combined estimates of the relative risk, and a meta-regression analysis of melanoma relative risk compared to leukemia relative risk was used to examine consistency across exposure categories. Generally, exposure categories with elevated relative risks of leukemia had proportionately elevated relative risks of melanoma. This suggests that people exposed to ionizing radiation may be at increased risk of developing melanoma, although alternative explanations are possible. Future epidemiological studies of ionizing radiation effects should include melanoma as an outcome of interest.

Aircraft↗
PubMedDate not supplied

Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure.

BACKGROUND: Chronic renal failure is complicated by secondary hyperparathyroidism, which traditionally has been controlled by dietary restriction of phosphorus and administration of phosphorus binders. Early treatment of patients with chronic renal failure with calcitriol may be indicated because once established, parathyroid gland hyperplasia does not readily resolve with therapy. HYPOTHESIS: Daily and intermittent dosing of calcitriol will decrease plasma parathyroid hormone concentration in normal cats and cats with chronic renal failure without causing ionized hypercalcemia. ANIMALS: Ten normal cats; 10 cats with chronic renal failure. METHODS: Phase 1 was daily calcitriol administration (2.5 ng/kg PO q24h) for 14 days. Phase 2 was intermittent calcitriol administration (8.75 ng/kg PO q84h) for 14 days. A 7-day washout period separated phases 1 and 2. Before each phase, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured. On days 1, 2, and 3 of both phases, serum ionized calcium concentrations were measured. On the last day of both phases, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured 0, 2, 4, and 6 hours after calcitriol administration. RESULTS: Overall, serum parathyroid hormone concentrations were significantly higher in cats with chronic renal failure than in normal cats (P = .022), but serum parathyroid hormone concentrations for both normal cats and cats with chronic renal failure were not significantly different before and after 14 days of treatment with calcitriol, regardless of whether calcitriol was administered daily or intermittently. Adverse effects of calcitriol administration (specifically ionized hypercalcemia) were not seen in either feline group during either phase of the study over the 3-day evaluation after calcitriol administration was initiated. CONCLUSIONS AND CLINICAL IMPORTANCE: At the dosages used, calcitriol treatment did not result in significant differences in serum parathyroid hormone concentrations before and after treatment in both normal cats and cats with chronic renal failure. With these dosages, adverse affects of calcitriol administration were not seen. Potential reasons for lack of apparent effect include small sample size, insufficient duration of study, insufficient dosage of calcitriol, problems with formulation or administration of calcitriol, and variable gastrointestinal absorption of calcitriol.

Administration, Oral↗
PubMed2003

Sensitivity of juvenile freshwater mussels (Lampsilis fasciola, Villosa iris) to total and un-ionized ammonia.

This study evaluated the sensitivity of juveniles of two freshwater unionid mussel species (Villosa iris [Lea] and Lampsilis fasciola [Rafinesquel) to un-ionized and total ammonia. Five concentrations of ammonium chloride were tested using 96-h static-renewal toxicity tests at 12 and 20 degrees C. Based on their respective mean 96-h lethal concentration to 50% (LC50s), V. iris (0.11 mg/ L NH3-N) was more sensitive than L. fasciola (0.26 mg/L NH3-N). At 96 h, significant differences in sensitivity to un-ionized ammonia between the two temperatures were not observed for either species. Comparison of LC50s reported for other aquatic organisms to the 96-h LC50s calculated for juvenile L. fasciola and V. iris shows these two mussel species to be among the most sensitive to un-ionized ammonia. Based on reported levels of un-ionized ammonia in the aquatic environment from anthropogenic sources, un-ionized ammonia may be an important limiting toxicological factor to freshwater mussel populations.

Age Factors↗
PubMed2006

Real-time monitoring of monochlorinated benzene and polychlorinated biphenyls in the gas phase with on-line detection: High chemical selectivity of resonance-enhanced two-photon ionization.

The development of molecular spectroscopy has enabled us to select chlorinated aromatic hydrocarbons very rapidly. In particular, the laser ionization TOFMS (time-of-flight mass spectrometry) method is expected to be useful as an on-line, selective, and sensitive method. In the present work, real-time laser ionization TOFMS measurements were carried out on gaseous chlorinated aromatic hydrocarbons. The laser ionization method used resonance-enhanced two-photon ionization with the direct introduction of gas into the vacuum chamber. This method for analyzing aromatic hydrocarbons was developed using a pulsed supersonic molecular beam method. In the context of developing a highly selective and sensitive method, excitation of monochlorinated benzene at lambda = 263.07 nm was found to be effective in the wavelength region from 263 nm to 265 nm. Also the excitation of polychlorinated biphenyls at lambda = 266 nm was found to be substantially more effective than at lambda = 280, 300 or 320 nm. The achievable sensitivity for real-time (1 min) measurements using the laser ionization TOFMS technique was found to be in the ppbV range.

Journal Article↗
PubMed2006

Effect of whole blood clotting time in rats with ionized hypocalcemia induced by rapid intravenous citrate infusion.

Although the toxic effects of citrate including hemodynamic and cardiovascular changes result from a decrease in ionized calcium levels in serum due to chelating action, these effects of citrate on blood coagulation have not yet been fully clarified. The present study examines whether serum citrate and ionized calcium levels affect whole blood clotting time in rats using the test tube method in which citrate is administered by rapid intravenous infusion. Citrate was infused via the tail vein into 10 rats at 3, 4 or 5 mmol/kg/hr for 1 hr, and then whole blood clotting time, serum citrate and ionized calcium levels were determined. Whole blood clotting time did not significantly change at citrate infusion rates of 3 and 4 mmol/kg/hr. However, at 5 mmol/kg/hr, whole blood clotting time was significantly prolonged by a factor of 2.1 relative to the untreated group, when the serum citrate level was 10.03 +/- 1.39 mmol/l (59.0-fold higher than that in the untreated group) and the serum-ionized calcium level was 0.29 +/- 0.02 mmol/l (0.2-fold lower than that in the untreated group). These results suggest that whole blood clotting time is significantly prolonged in rats with severe ionized hypocalcemia.

Animals↗
PubMed1995

Zinc heparin introduces a preanalytical error in the measurement of ionized calcium concentration.

In this study we determined how zinc heparin affected ionized calcium concentration determinations. Zinc heparin produced a positive bias (0.020-0.067 mmol l-1) in ionized calcium measurement in serum/whole blood and a negative bias (-0.035 to -0.110 mmol l-1) with aqueous ionized calcium standards. To test if the positive bias was due to zinc ions displacing calcium from its protein-calcium complexes, we reproduced the effect by adding ZnCl2 to pooled serum. Changes in [ZnCl2] (0.1-0.5 mmol l-1) caused a dose-dependent increase, a constant bias ([ZnCl2], 0.5-1.25 mmol l-1) or a dose-dependent decrease ([ZnCl2] > 1.25 mmol l-1) in ionized calcium concentration, independent of pH. Similar results were obtained when zinc concentration of the specimen was changed by varying the volume of blood collected into syringes containing zinc heparin. We conclude that zinc heparin produces a positive bias in ionized calcium measurement in protein-based matrices.

Binding Sites↗
PubMed1996

Relationship between ionized and total magnesium in serum.

The relationship between the concentration of ionized magnesium and total magnesium was investigated. Ionized magnesium was determined by an ion-selective electrode (Microlyte 6, KONE) and the result was adjusted to pH 7.4. Total magnesium concentration was measured by flame atomic absorption spectrometry. Total and ionized magnesium were only closely related in marked hypermagnesaemia (> 1.2 mmol/L), but correlation was poor in samples with slightly elevated total concentration or in hypomagnesaemia (< 0.65 mmol/L). The relationship was dependent on protein concentration. The agreement between total and ionized magnesium was acceptable in normoproteinaemia, but in hypoproteinaemia (< 40 g/L) total magnesium concentration was classified in 35% of the samples as below or within the reference interval, whereas the pertinent ionized magnesium concentration was normal or elevated, instead. Studies on paraproteinaemic sera clearly demonstrated that albumin concentration is most important for the size of the protein bound fraction.

Blood Proteins↗
PubMed1979

Calcium measurements in serum and plasma--total and ionized.

This article will review the methods currently employed for measuring the concentrations of total and ionized calcium in serum or plasma. As far as total calcium is concerned, various techniques such as atomic absorption spectrometry, spectrophotometry, fluorometry, complexometric titration, and flame photometry will be described and compared. Particular emphasis will be given to the accuracy and precision of each technique. Possible sources of error and interfering agents will be identified and the various procedures for the taking and handling of blood samples evaluated. Inter-laboratory variation in the measurement of calcium will be studied. An assessment will be made of a new reference method for measuring total calcium in serum using isotope-dilution mass spectrometry. The usefulness of the total calcium measurement in clinical medicine will be briefly discussed. Within the last decade the refinement of spectrophotometric techniques and the improvements in ion-selective electrode technology have revolutionized the measurement of ionized calcium in serum, such that it may now be possible to replace total calcium measurements with ionized calcium measurements on a routine basis. The various techniques currently in use for measuring ionized calcium will be described and evaluated. Particular attention will be paid to the preparation of standards, the procedures for taking blood samples, and the handling of the samples prior to and during measurement. An assessment of the relative value of measuring total and ionized calcium will be presented.

Calcium↗
PubMed2002

Effect of "ionized" wrist bracelets on musculoskeletal pain: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess objectively the perceived benefits of wearing an "ionized" wrist bracelet to treat muscle or joint pain. SUBJECTS AND METHODS: This study was performed at the Mayo Clinic in Jacksonville, Fla, in 2000 and 2001. In a randomized, double-blind design, 305 participants wore an ionized bracelet and 305 wore a placebo bracelet for 4 weeks. For each location where pain was present at baseline, participants rated the intensity of pain. Follow-up ratings were made after 1, 3, 7, 14, 21, and 28 days of wearing the bracelet. Two primary end points were defined for evaluating efficacy. The first was the change at 4-week follow-up (day 28) in the pain score at the location with the highest baseline value (maximum pain score). The second was the change at 4-week follow-up in the sum of the pain scores for all locations. RESULTS: Analysis of the data showed significant improvement in pain scores in both groups, but no differences were observed between the group wearing the placebo bracelet and the group wearing the ionized bracelet. CONCLUSION: The finding that subjective improvement in pain scores was equivalent with ionized and placebo bracelet use questions the benefit of using an ionized bracelet. New treatments in alternative medical therapy must be shown to be effective through vigorous, unbiased, objective testing before physicians acknowledge potential benefits or recommend these treatments to patients.

Adolescent↗