Proceedings of the First Workshop Organized by the IAFSS Working Group on Measurement and Computation of Fire Phenomena (MaCFP).

This paper provides a report of the discussions held at the first workshop on Measurement and Computation of Fire Phenomena (MaCFP) on June 10-11 2017. The first MaCFP work-shop was both a technical meeting for the gas phase subgroup and a planning meeting for the condensed phase subgroup. The gas phase subgroup reported on a first suite of experimental- computational comparisons corresponding to an initial list of target experiments. The initial list of target experiments identifies a series of benchmark configurations with databases deemed suitable for validation of fire models based on a Computational Fluid Dynamics approach. The simulations presented at the first MaCFP workshop feature fine grid resolution at the millimeter- or centimeter- scale: these simulations allow an evaluation of the performance of fire models under high-resolution conditions in which the impact of numerical errors is reduced and many of the discrepancies between experimental data and computational results may be attributed to modeling errors. The experimental-computational comparisons are archived on the MaCFP repository [1]. Furthermore, the condensed phase subgroup presented a review of the main issues associated with measurements and modeling of pyrolysis phenomena. Overall, the first workshop provided an illustration of the potential of MaCFP in providing a response to the general need for greater levels of integration and coordination in fire research, and specifically to the particular needs of model validation.

Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

BACKGROUND AND OBJECTIVES: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. METHODS AND RESULTS: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. CONCLUSIONS: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry.

Climate change interactions affect soil carbon dioxide efflux and microbial functioning in a post-harvest forest.

Forest disturbances, including whole-tree harvest, will increase with a growing human population and its rising affluence. Following harvest, forests become sources of C to the atmosphere, partly because wetter and warmer soils (relative to pre-harvest) increase soil CO2 efflux. This relationship between soil microclimate and CO2 suggests that climate changes predicted for the northeastern US may exacerbate post-harvest CO2 losses. We tested this hypothesis using a climate-manipulation experiment within a recently harvested northeastern US forest with warmed (H; +2.5 °C), wetted (W; +23% precipitation), warmed + wetted (H+W), and ambient (A) treatments. The cumulative soil CO2 effluxes from H and W were 35% (P = 0.01) and 22% (P = 0.07) greater than A. However, cumulative efflux in H+W was similar to A and W, and 24% lower than in H (P = 0.02). These findings suggest that with higher precipitation soil CO2 efflux attenuates rapidly to warming, perhaps due to changes in substrate availability or microbial communities. Microbial function measured as CO2 response to 15 C substrates in warmed soils was distinct from non-warmed soils (P < 0.001). Furthermore, wetting lowered catabolic evenness (P = 0.04) and fungi-to-bacteria ratios (P = 0.03) relative to non-wetted treatments. A reciprocal transplant incubation showed that H+W microorganisms had lower laboratory respiration on their home soils (i.e., home substrates) than on soils from other treatments (P < 0.01). We inferred that H+W microorganisms may use a constrained suite of C substrates that become depleted in their "home" soils, and that in some disturbed ecosystems, a precipitation-induced attenuation (or suppression) of soil CO2 efflux to warming may result from fine-tuned microbe-substrate linkages.

Neutron reflectometry studies on the lithiation of amorphous silicon electrodes in lithium-ion batteries.

Neutron reflectometry is used to study in situ the intercalation of lithium into amorphous silicon electrodes. The experiments are done using a closed three-electrode electrochemical cell setup. As a working electrode, an about 40 nm thick amorphous silicon layer is used that is deposited on a 1 cm thick quartz substrate coated with palladium as a current collector. The counter electrode and the reference electrode are made of lithium metal. Propylene carbonate with 1 M LiClO4 is used as an electrolyte. The utility of the cell is demonstrated during neutron reflectometry measurements where Li is intercalated at a constant current of 100 µA (7.8 µA cm(-2)) for different time steps. The results show (a) that the change in Li content in amorphous silicon and the corresponding volume expansion can be monitored, (b) that the formation of the solid electrolyte interphase becomes visible and (c) that an irreversible capacity loss is present.

Characterization of non-stoichiometric co-sputtered Ba0.6Sr0.4(Ti (1-x)Fe(x))(1+x)O(3-δ) thin films for tunable passive microwave applications.

The fabrication of novel iron-doped barium strontium titanate thin films by means of radio frequency (RF) magnetron co-sputtering is shown. Investigations of the elemental composition and the dopant distribution in the thin films obtained by X-ray photoelectron spectroscopy, Rutherford backscattering spectrometry, and time-of-flight secondary ion mass spectroscopy reveal a homogeneous dopant concentration throughout the thin film. The incorporation of the iron dopant and the temperature-dependent evolution of the crystal structure and morphology are analyzed by electron paramagnetic resonance spectroscopy, X-ray diffraction, Raman spectroscopy, atomic force microscopy, and scanning electron microscopy. In summary, these results emphasize the RF magnetron co-sputter process as a versatile way to fabricate doped thin films.

Strain relaxation and vacancy creation in thin platinum films.

Synchrotron based combined in situ x-ray diffractometry and reflectometry is used to investigate the role of vacancies for the relaxation of residual stress in thin metallic Pt films. From the experimentally determined relative changes of the lattice parameter a and of the film thickness L the modification of vacancy concentration and residual strain was derived as a function of annealing time at 130 °C. The results indicate that relaxation of strain resulting from compressive stress is accompanied by the creation of vacancies at the free film surface. This proves experimentally the postulated dominant role of vacancies for stress relaxation in thin metal films close to room temperature.

Induction of protective cytotoxic T cell responses in the presence of high titers of virus-neutralizing antibodies: implications for passive and active immunization.

The effect of preexistent virus-neutralizing antibodies on the active induction of antiviral T cell responses was studied in two model infections in mice. Against the noncytopathic lymphocytic choriomeningitis virus (LCMV), pretreatment with neutralizing antibodies conferred immediate protection against systemic virus spread and controlled the virus below detectable levels. However, presence of protective antibody serum titers did not impair induction of antiviral cytotoxic T lymphocyte (CTL) responses after infection with 10(2) PFU of LCMV. These CTLs efficiently protected mice independent of antibodies against challenge with LCMV-glycoprotein recombinant vaccinia virus; they also protected against otherwise lethal lymphocytic choriomeningitis caused by intracerebral challenge with LCMV-WE, whereas transfused antibodies alone did not protect, and in some cases even enhanced, lethal lymphocytic choriomeningitis. Against the cytopathic vesicular stomatitis virus (VSV), specific CTLs and Th cells were induced in the presence of high titers of VSV-neutralizing antibodies after infection with 10(6) PFU of VSV, but not at lower virus doses. Taken together, preexistent protective antibody titers controlled infection but did not impair induction of protective T cell immunity. This is particularly relevant for noncytopathic virus infections since both virus-neutralizing antibodies and CTLs are essential for continuous virus control. Therefore, to vaccinate against such viruses parallel or sequential passive and active immunization may be a suitable vaccination strategy to combine advantages of both virus-neutralizing antibodies and CTLs.

Light-induced cross-linking and post-cross-linking modification of polyglycidol.

The photoinduced radical generation process has received renewed interest due to its economic and ecological appeal. Herein the light-induced cross-linking of functional polyglycidol and its post-cross-linking modification are presented. Linear polyglycidol was first functionalized with a tertiary amine in a two-step reaction. Dimethylaminopropyl functional polyglycidol was cross-linked in a UV-light mediated reaction with camphorquinone as a type II photoinitiator. The cross-linked polyglycidol was further functionalized by quaternization with various organoiodine compounds. Aqueous dispersions of the cross-linked polymers were investigated by means of DLS and zeta potential measurements. Polymer films were evaluated by DSC and XPS.

QTc prolongation during erythromycin used as prokinetic agent in ICU patients.

BACKGROUND: High-dose erythromycin used as antibiotic prolongs QTc interval. Low-dose erythromycin is frequently used as a prokinetic agent, especially in patients in the intensive care unit (ICU). It is unknown whether low-dose erythromycin affects cardiac repolarisation and puts patients at risk for torsades de pointes. METHODS: In this prospective study, we included ICU patients treated with erythromycin as prokinetic in a dose of 200 mg twice a day. An ECG was performed before, 15 min and 24 hours after the start of erythromycin. Cardiac repolarisation was assessed by rate-corrected analysis of the QT interval (QTc) on the ECG by two independent investigators. Starting or stopping other possibly QTc prolonging drugs during the study period was an exclusion criterion. Wilcoxon signed-rank test and Friedman's test were used for statistical analysis to assess prolongation of QTc. Primary outcome was defined by the prolongation of QTc after 15 min and 24 hours. RESULTS: 51 patients were eligible for this study. In these patients, QTc increased significantly from 430 ms at baseline to 439 ms (p=0.03) after 15 min and 444 ms (p=0.01) after 24 hours. After 15 min and 24 hours, the upper limit of 95% CI for prolongation of QTc was well above 10 ms. No QTc-related arrhythmias were seen. CONCLUSIONS: During treatment with erythromycin in a dose of 200 mg twice a day. QTc prolonged mildly but significantly. Sequential ECG registration should be performed when low-dose erythromycin is prescribed, especially in the presence of other risk factor for QTc prolongation.

[Problems in the vocational rehabilitation of mentally ill subjects--a simple procedure to identify persons with an increased risk for premature termination of a training programme]. / Probleme der beruflichen Rehabilitation psychisch kranker Menschen--Ein einfaches Verfahren zur Erkennung von Personen mit erhöhtem Risiko für vorzeitigen Abbruch einer Massnahme.

UNLABELLED: A small number of young mentally ill persons consumes a disproportionate amount of psychiatric service resources. These persons are characterised by emotional instability, aggressive or delinquent behaviour, substance misuse and personality disorders. They are sometimes referred to as young adult chronic patients (YACP). To date there has been no investigation as to what impact this pattern of problem behaviour has on vocational rehabilitation. AIM: The aim of this study was to find out whether belonging to the YACP group, as determined by an operational definition, reduces the outcome of vocational rehabilitation. METHOD: A chart review was done of the files of all 174 participants of a 15-month vocational training course held between 1.1.1993 and 2.5.1998 in the vocational training centre at Cologne. A 15-item score was used to assess YACP status. RESULTS: 30 % were classified as high scorers, i. e. YACP. 59 % of the high scorers vs. 22 % of the low scorers terminated training prematurely. Of the high scorers who completed training, only 47 (vs. 74 % of low scorers) were judged to be able to work at the end of training. CONCLUSION: At the very beginning of the vocational training persons in need of a highly individualised format can be discerned by a few, easy to assess items. Concepts of vocational training should be developed to better suit the needs of young mentally ill persons with personality disorders and substance abuse.

Protection of yttria-stabilized zirconia for dental applications by oxidic PVD coating.

In this study, the application of transparent physical vapor deposition (PVD) coatings on zirconia ceramics was examined as an approach to retard the low-temperature degradation of zirconia for dental applications. Transparent monolayers of titanium oxide (TixOy) and multilayers consisting of titanium oxide-alumina-titanium oxide (TixOy-AlxOy-TixOy) were deposited onto standardized discs of 3Y-TZP using magnetron sputtering. Using X-ray photospectroscopy and time-of-flight secondary-ion mass spectrometry, the compositions of the coatings were verified, and an approximate thickness of 50 nm for each type of coating was ascertained. After aging the coated and uncoated samples in water vapor at 134°C and 3 bar for 4, 8, 16, 32, 64 and 128 h, the monoclinic phase content was determined using X-ray diffraction, and its impact on mechanical properties was assessed in biaxial flexural strength tests. In addition, the depth of the transformation zone was measured from scanning electron microscopy images of the fracture surfaces of hydrothermally aged samples. The results revealed that the tetragonal-to-monoclinic phase transformation of the zirconia ceramic was retarded by the application of PVD coatings. During the first stages of aging, the coated samples exhibited a significantly lower monoclinic phase content than the uncoated samples and, after 128 h of aging, showed a transformation zone which was only ∼12-15 µm thick compared to ∼30 µm in the control group. Biaxial flexural strength decreased by ∼10% during aging and was not influenced by the application of a PVD coating.

Evidence that low plasma 1,25-dihydroxyvitamin D causes intestinal malabsorption of calcium and phosphate in juvenile X-linked hypophosphatemic mice.

X-linked hypophosphatemic (Hyp) mice are a model for human sex-linked vitamin D-resistant rickets. We have reported intestinal malabsorption of calcium in young Hyp mice, and in this report we have explored the mechanism for it. To test for resistance of the intestine to 1,25(OH)2 vitamin D3, this hormone was continually infused via osmotic minipumps into 4-week-old normal and Hyp mice at 0, 17, 50 or 150 ng/kg/day. After 3 days, 45Ca and inorganic 32P were administered by gavage, and the mice were sacrificed on the fifth day. The Hyp mice showed responses to the hormone equivalent to the normal mice in terms of increased intestinal absorption of both 45Ca and 32P, increased plasma isotope levels, increased femoral isotope content, and increased duodenal and renal 9 kD vitamin D-dependent calcium-binding protein (calbindin-D9K; CaBP). Plasma 1,25(OH)2D was measured in these mice. There were significant correlations of plasma 1,25(OH)2D to the intestinal absorption of 45Ca and 32P and to duodenal and renal CaBP. Plasma 1,25(OH)2D was also measured in stock normal and Hyp mice and was found to be lower in 4-week-old Hyp mice than in 4-week-old normal mice (113 +/- 10 pM (n = 18) vs. 67 +/- 10 (n = 20), normal vs. Hyp, p less than .01), but unchanged at 13 weeks of age (77 +/- 13 (n = 13) vs. 70 +/- 15 (n = 15), NS). This observed difference in plasma 1,25(OH)2D between normal and Hyp mice at 4 weeks of age was sufficient to explain the observed normal-to-Hyp differences in intestinal absorption of 45Ca and duodenal and renal CaBP. It also explained 72 +/- 18% of the observed difference in 32P absorption. We conclude that Hyp mouse intestine is not resistant to 1,25(OH)2D and that the lower plasma 1,25(OH)2D of 4-week-old Hyp mice causes intestinal malabsorption of calcium and phosphate.

Effect of 1,25,28-trihydroxyvitamin D2 and 1,24,25-trihydroxyvitamin D3 on intestinal calbindin-D9K mRNA and protein: is there a correlation with intestinal calcium transport?

Although analogs and metabolites of vitamin D have been tested for their calciotropic activity, very little information has been available concerning the effects of these compounds on gene expression. In this study one analog of vitamin D, 1,25,28-trihydroxyvitamin D2 [1,25,28-(OH)3D2], and one metabolite, 1,24,25-trihydroxyvitamin D3 [1,24,25-(OH)3D3], were tested for their effect on intestinal calbindin-D9K mRNA and protein as well as for their effect on intestinal calcium absorption and bone calcium mobilization. These compounds were also evaluated for their ability to compete for rat intestinal 1,25-(OH)2D3 receptor sites and to induce differentiation of human leukemia (HL-60) cells as indicated by reduction of nitro blue tetrazolium. In vivo studies involved intrajugular injection of 12.5 ng 1,25-(OH)2D3 or test compound to vitamin D-deficient rats and sacrifice after 18 h. 1,25,28-Trihydroxyvitamin D2 had no effect on intestinal calcium absorption, bone calcium mobilization, or intestinal calbindin-D9K protein and mRNA. Competitive binding to 1,25-(OH)2D3 receptors was 0.8% of that observed using 1,25-(OH)2D3. However, 20- and 40-fold higher doses of 1,25,28-(OH)3D2 (250 and 500 ng) resulted in significant inductions in calbindin-D9K protein and mRNA (3.5 to 7.4-fold), although doses as high as 800 ng were found to have no effect on intestinal calcium absorption or bone calcium mobilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Novel fibroblast-specific monoclonal antibodies: properties and specificities.

Specific detection of fibroblasts has been one of the unsolved problems in cell biology. Because monoclonal antibodies (MoAbs) might provide an easy and reproducible method of fibroblast detection, we have produced a panel of MoAbs raised against cell surface proteins of human dermal fibroblasts. Using flow cytometry and immunohistochemistry, we have shown that two of these MoAbs, FibAS01 and FibAS02, react exclusively with human fibroblasts. They do not react in vitro with human keratinocytes, endothelial cells, or blood cells. Immunohistologic experiments investigating the binding pattern of the MoAbs FibAS01 and FibAS02 in cryostat sections of different tissues confirmed the flow cytometric results. In human skin, the antibodies exclusively labeled fibroblasts. In other human tissues such as lymph nodes, placenta, kidney, muscle, thyroid gland, gall bladder, cartilage, and tendon, the specificity for fibroblasts was borne out. Neither antibody reacts with fibroblasts from mouse, rat, or pig. The isotype was defined as an IgG1 for both. By western blot analysis, both antibodies detected a molecule of 60-65 kDa under reducing and nonreducing conditions. By immunoelectron microscopy, we observed the antigens on the cell surface without any clustering at specific sites. These data demonstrate that the two MoAbs, FibAS01 and FibAS02, exclusively recognize human fibroblasts.

Skin fibroblasts are the only source of nidogen during early basal lamina formation in vitro.

The purpose of this study was to determine whether nidogen, the linkage protein of the basal lamina, is of epidermal or dermal origin. The development of the basal lamina was studied in an in vitro skin model. Preputial fibroblasts seeded onto a nylon mesh attached, proliferated, and developed a rich extracellular matrix (dermal model). Preputial keratinocytes were added to the dermal model to form a keratinocyte dermal model that ultrastructurally resembled in many respects human skin. Ultrastructural analysis revealed early stages of dermal development, including an incomplete basal lamina, aggregates of dermal filamentous material connecting to the lamina densa, bundles of 10-nm microfibrils, formation of premature hemidesmosomes, anchoring filaments, and anchoring fibrils. The cell origin of nidogen was determined in the dermal model and in the epidermal and dermal components of the keratinocyte dermal model. Specific antibodies and a cDNA probe for nidogen were used for immunofluorescence microscopy, Western and Northern blots, and for in situ hybridization studies. Our data show that fibroblasts are the only source of nidogen during early basal lamina formation. Although fibroblasts can synthesize nidogen and deposit it in the dermal matrix, no basal lamina will form unless they are recombined with keratinocytes. This suggests that the epidermis plays a major regulatory role in the production and assembly of nidogen into the basal lamina.

Presence and localization of two vitamin D-dependent calcium binding proteins in kidneys of higher vertebrates.

We looked for the presence of vitamin D-dependent intestinal calcium binding protein (CaBP), relative molecular mass (mol wt) about 10,000, in kidneys of mammals, birds, and reptiles, and compared the localization of this 10,000 mol wt CaBP with the localization of the 28,000 mol wt vitamin D-dependent CaBP. Antiserum directed against rat intestinal CaBP (RICaBP) was used with the unlabeled antibody peroxidase-antiperoxidase technique to localize the 10,000 mol wt CaBP. Kidneys of adult Swiss and DBA/2J mice were positive for the 10,000 mol wt CaBP, whereas kidneys of adult rat, chicken, and two species of lizard were negative. Extracts of adult rat kidney showed no detectable immunoreactivity with the antiserum to RICaBP by radial immunodiffusion assay. However, kidneys of postnatal rats (12 days old) exhibited limited immunocytochemical reactivity and relatively low immunoreactivity (about 1 micrograms/mg protein) for 10,000 mol wt CaBP. In both strains of mice, 10,000 mol wt CaBP was localized predominantly to the distal convoluted tubules, connecting tubules, and collecting tubules of the cortical labyrinth. In 12-day-old rats 10,000 mol wt CaBP was localized to the distal convoluted tubules and cortical ascending thick limbs. Absorption of the antiserum with electrophoretically pure RICaBP eliminated specific reactivity. By dual color staining of mouse kidneys, the population of cells reactive for the 10,000 mol wt CaBP was found to be similar, but not identical, to that population of cells reactive for the 28,000 mol wt CaBP. Absorption of the antiserum to RICaBP with either rat renal CaBP or chicken intestinal CaBP (both 28,000 mol wt CaBPs) had no affect on the positive reactivity of the distal mouse nephron for RICaBP. Conversely, absorption of the antiserum to rat renal CaBP with the 10,000 mol wt RICaBP had no affect on reactivity for the 28,000 mol wt CaBP. Thus, two immunologically distinct CaBPs, mol wt 10,000 and 28,000, are present in the adult mouse nephron; whereas, kidneys of adult rats, chickens, and saurian reptiles apparently contain significant levels of only 28,000 mol wt CaBP. Since the 12-day-old rat nephron contains both the 28,000 mol wt and the 10,000 mol wt CaBP it appears that in the kidney, ontogenetically, and perhaps evolutionarily as well, the 28,000 mol wt CaBP is more highly conserved.

Regulation by dietary calcium of vitamin D-dependent calcium-binding protein and active calcium transport in the small intestine of lactating rats.

To test the hypothesis that vitamin D-dependent calcium-binding protein (CaBP) and active calcium (Ca) transport in the small intestine of vitamin D-replete lactating rats are regulated by dietary Ca intake, pregnant rats were given a high Ca (1.6% Ca and 1.4% phosphorus) or low Ca (0.1% Ca and 0.4% phosphorus) diet starting 3 days before delivery. Toward the end of lactation (days 16-23) the rats were killed, and active Ca transport (using everted gut sacs) and CaBP were determined in duodenum, jejunum, and ileum. The right tibiae were used for bone weight and ash determinations. The Ca transport ratios and CaBP concentrations in jejunum and ileum were significantly increased only in the low Ca group. In contrast, in the duodenum both parameters were equally high regardless of the diet. Nonlactating rats given the two diets for the same length of time had the expected increase in both parameters in the duodenum when fed the low Ca diet. Nonlactating rats, in contrast to lactating rats, had undetectable CaBP in jejunum and ileum regardless of diet. Lactating rats fed the high Ca diet had no net loss of bone at the end of lactation compared with rats on day 1 of lactation. In contrast, lactating rats fed the low Ca diet had a net loss of 44% of bone weight. Plasma 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] concentrations on the 21st day of lactation were (mean +/- SE) 538 +/- 96 and 46 +/- 18 pg/ml in rats consuming the low and high Ca diets, respectively. The comparable values for the nonlactating rats were 140 +/- 4 and 26 +/- 8 pg/ml. In conclusion, dietary Ca restriction during lactation can stimulate CaBP and active Ca transport in both jejunum and ileum, and both parameters appear to be modulated by dietary Ca via the circulating concentration of 1,25-(OH)2D3. In contrast, in the duodenum neither parameter appears to be related to dietary Ca, plasma 1,25-(OH)2D3 concentration, or lactation-associated bone loss.

Vitamin D-dependent calcium-binding protein of rat intestine: changes during postnatal development and sensitivity to 1,25-dihydroxycholecalciferol.

To study the role of the vitamin D-endocrine system during the perinatal period, we monitored vitamin D-dependent calcium-binding protein (CaBP) in rat intestine by radial immunodiffusion and polyacrylamide disc gel electrophoresis. Small amounts of CaBp were present 2 days before birth; these levels increased 74-fold by day 38 after birth. Approximately 80% of the increase in CaBP concentration occurred in a 5-day period at the time of weaning (days 17--22 after birth). Before this period, the concentration of CaBP was comparable to that found in rachitic (adult) rats. Administration of 1,25-dihydroxycholecalciferol to suckling rats on days 15 and/or 16 was followed by a premature increase in the amount of intestinal CaBP. These data demonstrate that although vitamin D-dependent CaBP is low in preweaned rats, the rat intestine is responsive to exogeneous 1,25-dihydroxyvitamin D3 at least as early as day 15 after birth. The close temporal correspondence between the increases in CaBP and previously reported changes in calcium transport and vitamin D metabolism suggest that the vitamin D-endocrine system plays a role in postnatal intestinal maturation and adaptation during the weaning period.

Elevated levels of vitamin D-dependent calcium-binding protein (calbindin-D9k) in the osteosclerotic (oc) mouse.

The osteosclerotic (oc) mouse is an osteopetrotic mutation that has recently been identified as having rickets associated with its osteopetrosis. The presence of this rachitic lesion, unexplainable from a nutritional standpoint, prompted an investigation into the vitamin D endocrine system in these animals. The developmental appearance of vitamin D-dependent calcium-binding protein (calbindin-D9k) and alkaline phosphatase was studied in oc mutant and normal mice from birth to weaning, as were serum concentrations of 25-hydroxyvitamin D3 (25OHD3), 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], calcium, and phosphorus. Intestinal and renal calbindin-D9k levels were markedly and precociously elevated (4- to 9-fold) in young suckling, but not newborn, mutant mice compared to values in normal controls. Serum 25OHD3 levels were very low to undetectable in 2-week-old mutant mice compared to normal values, while 1,25-(OH)2D3 levels were 6 times higher in mutants. The exact cause of this premature induction in mutants is unknown, but may be due to elevated circulating levels of 1,25-(OH)2D. Alkaline phosphatase activity was similar between phenotypes at all ages. These studies indicate that the rachitic lesion present in oc mutants may be the result of some inherited disorder in vitamin D metabolism in these animals. Alternatively, these data are also consistent with a normal appropriate response to hypocalcemia and hypophosphatemia resulting from decreased osteoclastic bone resorption.

Low levels of intestinal vitamin D-dependent calcium-binding protein in juvenile X-linked hypophosphatemic mice.

Hyp mice are a model for human X-linked hypophosphatemia, the most common form of vitamin D-resistant rickets. The developmental appearance of intestinal vitamin D-dependent calcium-binding protein (CaBP) and alkaline phosphatase was studied in Hyp mice and normal mice from the perinatal period to adulthood. Both intestinal proteins were increased in the duodenum during weeks 2 and 3 of age, with values rising 10-fold or more above values measured in intestines of 1-week-old mice. During this developmental period and at most other ages, Hyp mice had levels of alkaline phosphatase and total intestinal protein comparable to those in control mice. On the other hand, the concentration of intestinal CaBP was decreased in juvenile Hyp mice during the weaning period at 2-3 weeks of age (35-65% of normal) and further depressed in the rapid growth phase at 4-6 weeks of age (15-45% of normal). During adulthood (7-35 weeks of age) Hyp mice maintained a CaBP concentration that averaged 71% of the level of control mice. These maturational defects in the Hyp intestine may play a contributory role in the bone disease in young Hyp mice.