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Abstract: A left or right button press was frequently (85%) assigned to 0.5-s delayed feedback of a binaural high- or low-pitched tone, respectively. Neuromagnetic responses were recorded from eight subjects while executing a self-paced (~2 s) and self-chosen (∼50%) button press with their eyes closed. Infrequent occurrences (15%) of counter-assigned auditory feedback elicited mismatch negativity-like activities bilaterally localized in the vicinity of Heschl''s gyrus. The present result suggests that auditory perception is modulated by top–down prediction not only in visuoauditory but also in motor (kinesthetic)–auditory contexts. [Copyright &y& Elsevier]

Background/Aims: Although the PTH-suppressive effect of intravenous calcitriol has already been demonstrated by various studies, the precise dose-response to calcitriol has not been fully determined for uremic secondary hyperparathyroidism (2HPT). In order to investigate in detail the dose-response of intravenous calcitriol and the adequate initial dose against 2HPT, a randomized prospective double-blind study was conducted. Method: One-hundred and sixty-two patients with 2HPT undergoing hemodialysis three times per week were randomly assigned to four calcitriol (Ro21-5535) treatment groups, 0 (placebo), 1, 1.5 or 2 μg. Calcitriol or placebo was given intravenously after each dialysis for 12 weeks under double-blind conditions. Results: Calcitriol dose-dependently reduced both intact-PTH and high-sensitivity assay mid-terminal (HS)-PTH levels. The rate of per-week change in intact-PTH was 0.0% in the placebo group, –7.8% in the 1-μg group, –18.9% in the 1.5-μg group and –24.1% in the 2-μg group. Calcitriol dose-dependently increased the rate of increase in serum Ca adjusted by albumin level. The per-week increases in adjusted serum Ca were –0.01, 0.08, 0.23 and 0.35 mg/dl in the placebo, 1-, 1.5- and 2-μg groups, respectively. Although the degree of PTH suppression was correlated with the adjusted serum Ca increase, by-patients investigation revealed that the number of patients with suppression of PTH despite of no or slight elevation of adjusted serum Ca level was largest in the 1-μg group among the three calcitriol groups. Conclusion: Intravenous calcitriol was found to have a clear dose-dependent effect on PTH reduction in patients with 2HPT, and the appropriate initial dose of this agent was determined to be 1 μg per dialysis session.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To determine whether parathyroid hormone-related protein is synthesized and secreted by the tumor cells of patients with adult T-cell leukemia-lymphoma.Design and Patients: Convenience sample of three patients with adult T-cell leukemia-lymphoma. Two patients developed hypercalcemia, and one patient was normocalcemic.Setting: Inpatient facilities at two university-affiliated medical centers.Intervention: All patients had a lymph node biopsy. In addition, samples of ascitic or pleural fluid, or both, were obtained from these patients.Measurements and Results: Using RNA blot analysis, we showed that parathyroid hormone-related protein (PTHrP) messenger RNAs (mRNAs) were constitutively expressed in the tumor cells from all patients. Cyclic adenosine monophosphate (cAMP) production-stimulating activity, assessed using osteoblast-like UMR106 cells, was demonstrated in the pleural and ascitic fluids from the two patients who developed hypercalcemia. The elution profiles of the cAMP production-stimulating activity in the ascitic fluid extracts were very similar to those of the tumor extracts from hypercalcemic nude rats that had been implanted with a human cancer tumor.Conclusions: Parathyroid hormone-related protein is produced by tumor cells in adult T-cell leukemia-lymphoma, which may be an important factor in the development of hypercalcemia in the patients with this disease. However, the development of hypercalcemia may depend on other factors such as the number of tumor cells, access of the protein into systemic circulation, and the presence of some additional substances. [ABSTRACT FROM AUTHOR]

The action of GRF on GH3 cell membrane was examined by patch electrode techniques. Under current clamp with patch electrode, spontaneous action potentials were partially to totally eliminated by application of GRF. In the case of partial elimination, the duration of remaining spontaneous action potentials was prolonged and the amplitude of afterhyperpolarization was decreased. The evoked action potential in the cells which did not show spontaneous action potentials was also eliminated by GRF. In order to examine what channels were affected by GRF, voltage-clamp analysis was performed. It was revealed that voltage-gated Ca2+ channel current and Ca2+-induced K+ channel current were decreased by GRF, while voltage-gated Na+ channel and delayed K+ channel were not affected. The decrease of Ca2+-induced K+ channel current was considered to be a consequence of the decrease of voltage-gated Ca2+ channel current. Therefore it is likely that the effect of GRF on GH3 cells was due to the block of voltage-gated Ca2+ channels. The elimination of action potential under current clamp corresponded to the block of voltage-gated Ca2+ channels and the prolongation of action potential could be explained by the decrease of Ca2+-induced K+ channel current. The amplitude decrease of afterhyperpolarization could also be explained by the reduction of Ca2+-induced K+ channel current. Thus the results under current clamp well coincide with the results under voltage clamp. Hormone secretion from GH3 cells was not stimulated by GRF. However, the finding that GRF solely blocked voltage-gated Ca2+ channel suggested the specific action of GRF on GH3 cell membranes. [ABSTRACT FROM AUTHOR]

Previous reports demonstrated that the administration of large doses of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] to animals with normal vitamin D supply causes an increase in bone volume with reduced bone resorption and decreased osteoclast number. The present study was undertaken to clarify if 24R,25(OH)2D3 has any inhibitor effect on the formation and function of osteoclasts. The effect of 24R,25(OH)2D3 on the formation of osteoclastic cells was examined by measuring the number of tartrate-resistant acid phosphatase-positive multinucleated cells (MNCs) formed from hemopoietic progenitor cells obtained from spleens of 5-fluorouracil-treated mice. Treatment with 1,25(OH)2D3 or parathyroid hormone fragment 1-34 [PTH(1-34)] stimulated osteoclast-like MNC formation in a dose-dependent manner. Addition of 24R,25(OH)2D3 alone showed a weak stimulatory effect on MNC formation at 10(-6) M, which appeared to be due to its binding to 1,25(OH)2D3 receptors. In contrast, when 24R,25(OH)2D3 was added together with 1,25(OH)2D3 or PTH(1-34), it inhibited osteoclast-like MNC formation stimulated by these hormones. A significant inhibition of MNC formation was observed with 10(-7) M 24R,25(OH)2D3, and the stimulatory effect of 1,25(OH)2D3 or PTH(1-34) was almost completely eliminated with 10(-6) M 24R,25(OH)2D3. Neither 24S,25(OH)2D3 nor 25(OH)D3 exhibited a similar inhibitory effect. The effect of 24R,25(OH)2D3 on the resorptive function of osteoclasts was examined by measuring the formation of resorption pits by mouse bone cells on dentine slices. Treatment with 24R,25(OH)2D3 also inhibited the resorption pit formation stimulated by 1,25(OH)2D3 or PTH(1-34) with similar dose response.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

Tumors causing humoral hypercalcemia of malignancy (HHM) were implanted to athymic nude rats. In one of these rat models transplanted with uterine cancer (UCC), a complete reproduction of human HHM syndrome was achieved: hypercalcemia, hypophosphatemia with increased urinary phosphate and cyclic AMP excretion, and suppressed serum 1,25-dihydroxy-vitamin D (1,25(OH)2D) level. In another hypercalcemic nude rat model implanted with oral cavity cancer (OCC), all the features were similar except for markedly elevated serum 1,25(OH)2D. Hypercalcemia disappeared by surgical removal of the tumors in both models, confirming the humoral mechanisms for causing these features. Furthermore, in UCC tumor-bearing rats, hypophosphatemia, increased renal phosphate excretion, and reduced serum 1,25(OH)2D concentration were already present when these rats were only marginally hypercalcemic. These results raise the possibility that the changes in renal tubular phosphate handling and vitamin D metabolism in HHM are not secondary to hypercalcemia but are due to direct effects of the humoral factor(s) that cause this syndrome. Extracts of both tumors exhibited stimulation of cyclic AMP production in osteoblastlike cells, UMR 106, which could be almost completely inhibited by parathyroid hormone (PTH) antagonist, human PTH(3-34). By comparing the nature and characteristics of humoral factor(s) from UCC and OCC models, mechanisms responsible for causing these abnormalities can be explored. Thus, these nude rat models can be useful for elucidating the underlying mechanism of the development of HHM. [ABSTRACT FROM AUTHOR]

The direct effect of aluminum on mineralization was examined using an osteoblastlike cell line, MC3T3-E1. The mineralization process was quantitated by measuring 45Ca accumulation into the cell and matrix layer of MC3T3-E1 cells in culture. The accumulation of 45Ca into the cell and matrix layer increased dramatically after 13 days of culture without a parallel change in the DNA content of these cells. Because nodular clusters of cells appear around the same period in which a massive mineralization occurs, the marked increase in 45Ca accumulation after the 13th day of culture appears to represent deposition of 45Ca into the extracellular matrix. Thus, this culture system offers a useful model for making a quantitative estimation of osteoblast-mediated mineralization in vitro. When aluminum was added to this system, the accumulation of 45Ca into the cell matrix layer was inhibited in a dose-dependent manner: 10(-6) M aluminum reduced 45Ca accumulation to 40.8 +/- 2.7% of that in nontreated cells without affecting alkaline phosphatase activity or the DNA content of these cells. Because the concentration of aluminum used in this study is well within the range of serum aluminum levels seen in chronic dialysis patients, the direct effects of aluminum on osteoblast-mediated mineralization shown in the present study may underlie the development of so-called aluminum-induced "osteomalacia" in certain dialysis patients. [ABSTRACT FROM AUTHOR]

Notwithstanding the great importance of the salinity factor in the marine environment, the knowledge of influence of salinity on growth of marine benthic algae is very limited. Rate of growth (mg, cm) and O output of the intertidal red alga Porphyra umbilicalis from Helgoland, North Sea, were measured during a 3 week culture in 3 different salinities (1/2-, 1- and 2-concentrated artificial sea water; Table 1). Under hypertonic conditions (2-concentrated sea water) growth rate and photosynthesis rate were depressed, compared to values obtained in normal concentrated sea water. Under hypotonic conditions (1/2-concentrated sea water), growth expressed in mg was the same as in normal concentrated sea water, or higher when expressed in cm. Rate of O output was almost unaltered in one of the two experiments, lowered in the other. Cell size increased at higher salinity, while swelling of cell walls and intercellular substances as well as the intensity of colouring decreased with salinity. The discrepancies between growth and photosynthesis under hypotonic conditions cannot be completely explained by the observed influences of salinity on morphological structures (cell size, swelling of cell substances). Detailed studies on the time course of photosynthesis and respiration rates, and preparation of a metabolic balance for the algae are necessary. [ABSTRACT FROM AUTHOR]