Search PubMed⌕ Search

Biomedical subjects

G Weber

Publications and source records attributed to G Weber.

At least 127 records · Page 7Linked to original sources

Schistosomiasis presenting as acute appendicitis in a traveler.

Schistosomiasis, a waterborne trematode infestation, is one of the most widespread parasitic diseases in the world. It occurs in well-defined endemic geographical areas. Schistosomiasis of the appendix was first described by Turner in 1909, and has been reported from endemic areas. However, appendicular schistosomiasis in travelers has not been reported in the English literature. We describe an Israeli traveler with acute appendicitis as the presenting symptom of schistosomiasis, 2 years after a visit to Africa.

Acute Disease↗

Neonatal transient hypothyroidism: aetiological study. Italian Collaborative Study on Transient Hypothyroidism.

AIMS: To define the aetiology of neonatal transient hypothyroidism (NTH) and recommend preventive measures. METHODS: Maternal and perinatal clinical data on the use of antiseptics, drugs, and contrast agents containing iodine were collected from 40 subjects. Thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), thyroglobulin (TG), TSH receptor antibodies, thyroid peroxidase antibodies and urinary iodine were measured in random neonatal samples. In the mothers with known or suspected thyroid disorders, TSH, FT4, TSH receptor antibodies and thyroid peroxidase antibodies were also measured. RESULTS: The NTH aetiology was identified in 85% of cases. More than 50% of the babies with transient hypothyroidism had been exposed to iodine; maternal transfer of antibodies had occurred in a third of them. CONCLUSIONS: It is suggested that the practice of using iodine containing disinfectants should be withdrawn, and chlorhexidine substituted instead; that pregnant women should be advised of the adverse effects of using iodine products; and that thyroid function should be monitored whenever iodine is used.

Adult↗

Bronchial responsiveness in active steelworkers.

Coke-oven workers are exposed to dust and irritant gases. Therefore they are at risk of developing lung diseases including chronic bronchitis. Nonspecific bronchial hyperresponsiveness (BHR) has been advocated as a potential risk factor predisposing to the development of chronic bronchitis. In a previous study, we showed that prevalence of BHR was higher in retired coke-oven workers than in retired blast furnace workers. The present study was carried out to determine the prevalence of BHR in active steelworkers. Thus, 137 coke-oven workers and 150 blast furnace workers underwent clinical examination, a standardized questionnaire for the study of respiratory symptoms, pulmonary function testing and methacholine aerosol challenge. The study demonstrates a higher prevalence and degree of BHR [provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) < or = 8 mg x mL(-1)] in coke-oven workers than in blast furnace workers (31.4 versus 6.7%; p<0.001). Moreover, the frequency of respiratory symptoms and basal bronchial obstruction were greater among coke-oven workers with BHR in nonresponders. The basal maximum expiratory flow from 25-75% of forced vital capacity and the respiratory symptoms were correlated with bronchial responsiveness. The lack of correlation observed between BHR and the intensity of smoking or years spent in coke-oven environment may be explained by the high proportion of smokers, the worker turnover in the steel plant, and the "healthy worker effect". In conclusion, the higher prevalence and degree of bronchial hyperresponsiveness in coke-oven workers suggests that coke-oven pollutants are more intense irritants than those that escape from blast furnaces.

Adult↗

Alterations of the MEN1 gene in sporadic parathyroid tumors.

Primary hyperparathyroidism is a common endocrine disease that also occurs in a number of inherited disorders, including multiple endocrine neoplasia type 1 (MEN1). Loss of heterozygosity (LOH) in the MEN1 region on chromosome 11q13 has been found in 30% of sporadic parathyroid tumors, making the recently cloned MEN1 gene a prime candidate for involvement in parathyroid tumorigenesis. Using LOH and single strand conformation analysis, we screened 45 sporadic tumors from 40 patients for alterations involving the MEN1 gene. Thirteen tumors showed LOH at 11q13, and in 6 of these cases, somatic mutation of the MEN1 gene was detected. In tumors without LOH, no mutations were detected. The mutations consisted of 3 small deletions, 1 insertion, and 2 missense mutations that had not been reported in MEN1 patients or parathyroid tumors previously. Using messenger ribonucleic acid in situ hybridization, the expression of the MEN1 gene was studied. There was no difference in expression between normal and tumor tissue. In conclusion, the findings of inactivating mutation in tumors with LOH at 11q13 confirm the role of the MEN1 tumor suppressor gene in a subset of sporadic parathyroid tumors.

Adult↗

Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported. However, whether these families constitute MEN 1 variants or separate entities remains speculative as the genetic bases for these diseases are unclear. The gene for MEN 1 has recently been cloned and characterized. Using single strand conformation analysis (SSCA) and sequencing, we performed mutation analysis in: a) a total of 55 MEN 1 families from 7 countries, b) 13 isolated MEN 1 cases without family history of the disease, c) 8 acromegaly families, and d) 4 FIHP families. Mutations were identified in 27 MEN 1 families and 9 isolated cases. The 22 different mutations spread across most of the 9 translated exons and included frameshift (11), nonsense (6), splice (2), missense mutations (2), and in-frame deletions (1). Among the 19 Finnish MEN 1 probands, a 1466del12 mutation was identified in 6 families with identical 11q13 haplotypes and in 2 isolated cases indicating a common founder. One frameshift mutation caused by 359del4 (GTCT) was found in 1 isolated case and 4 kindreds of different origin and haplotypes; this mutation therefore represents a common "warm" spot in the MEN1 gene. By analyzing the DNA of the parents of an isolated case one mutation was confirmed to be de novo. No mutation was found in any of the acromegaly and small FIHP families, suggesting that genetic defects other than the MEN1 gene might be involved and that additional such families need to be analyzed.

Acromegaly↗

Characterization of the phosphatidylinositol-specific phospholipase C isozymes present in the bovine parathyroid and in human kidney HEK293 cells stably transfected with the human parathyroid Ca2+-sensing receptor.

The regulation of parathyroid hormone secretion by the chief cells of the parathyroid is mediated by a 7-transmembrane (7-TM) Ca2+-sensing receptor (CaR), which signals via activation of pertussis toxin-insensitive G proteins, causing stimulation of phosphatidylinositol-specific phospholipase C (PI-PLC). We have identified the PI-PLC isoforms expressed in two model systems utilized for studying CaR signal transduction, i.e. dispersed bovine parathyroid cells and a human embryonic kidney cell line (HEK 293) stably transfected with the human parathyroid CaR-cDNA. All of the eight PI-PLC isozymes examined in this study were found to be expressed to varying extents in the bovine parathyroid gland and in the CaR-transfected HEK cells as assessed by immunoblotting. We localized the expression of the more abundant isozymes (beta1, beta2, beta3, gamma1, gamma2, delta2) to the chief cells of the bovine parathyroid by immunocytochemistry, while the two less abundant isozymes (delta1, beta4) were not detectable in parathyroid sections. G proteins activated by 7-TM receptors are known to activate mainly PI-PLC of the beta class. Therefore, beta1, beta2, beta3 and beta4, all expressed in the bovine parathyroid, are candidate isozymes for coupling to the CaR. A comparison of the levels of expression of PI-PLC isozymes between CaR-transfected HEK cells and non-transfected HEK cells suggested that the expression of the CaR in this human cell line does not cause a significant up-regulation of any of the PLCbeta and PLCgamma isozymes. PLCdelta2, showing predominantly nuclear localization in the parathyroid, was the sole PI-PLC isozyme with higher levels of expression in CaR-transfected HEK cells.

Animals↗

Infective endocarditis in a tertiary-care hospital in southern Israel.

During the years 1980-1994, 84 patients were treated in our institution due to suspected infective endocarditis (IE). Seventy-one of these episodes occurring in 71 patients, classified definite or possible according to the Duke criteria, were retrospectively analyzed in this study. There were 52 cases of native valve endocarditis, 7 cases of early prosthetic valve endocarditis, and 12 cases of late prosthetic valve endocarditis. The incidence of IE did not change significantly during the study period. The overall mortality rate was 15%. Only one case of drug addiction appeared in our series despite its growing frequency in Israel. Rheumatic heart disease remained the main underlying cardiac condition and Streptococcus viridans remained the most common pathogen. Streptococcus bovis was found to be a significant pathogen causing IE in our patient population, while Staphylococcus aureus appeared to be less frequent. The Duke criteria significantly classified a greater proportion of cases as definitive, as opposed to the von Reyn criteria. Fewer cases were rejected by the Duke criteria, especially culture-negative cases, and those without histopathological confirmation. Application of the Duke criteria permits a more consistent approach to the diagnosis of IE, even in a non-drug-addict patient population.

Adolescent↗

Synergistic action of tiazofurin and genistein in human ovarian carcinoma cells.

Tiazofurin, an oncolytic drug, reduces PI kinase activity and arrests chiefly in S phase. Genistein, an inhibitor of PIP kinase, tyrosine kinase, and topoisomerase-II, induces arrest in G2 and/or early M phase in most carcinoma cells. Both tiazofurin and genistein reduce second messenger IP3 concentration in ovarian carcinoma cells. Because genistein and tiazofurin attack different enzymic targets and arrest the cell cycle at different phases, we tested the hypothesis that tiazofurin might be synergistic with genistein. Human ovarian carcinoma OVCAR-5 cells were grown in flasks in monolayers. In growth inhibition assay for tiazofurin and genistein the IC50s were 26 and 18 microM, respectively, and in clonogenic assays the LC50s were 17 and 4 microM, respectively. Various combinations of the two drugs were tested. The best protocol took into consideration that tiazofurin decreased GTP concentration in cells by 50% at 12 h after administration. Tiazofurin (20 microM) and genistein (20 microM) as single agents reduced cell counts to 60% and 50%, respectively. The predicted value, as a sum of the effect of two drugs, would have been 30% of controls. However, genistein added 12 h after tiazofurin decreased cell counts to 8%, showing synergistic action of the two drugs for growth inhibition. Similar results were observed in the clonogenic assays, which also revealed synergistic cytotoxicity. The protocol yielding synergism might be of value in the clinical treatment of human ovarian carcinoma.

Antineoplastic Agents↗

Tamoxifen downregulates signal transduction and is synergistic with tiazofurin in human breast carcinoma MDA-MB-435 cells.

Breast carcinoma is a leading cause of cancer death in women in the US. Tamoxifen (TAM), an antiestrogen, is used as a chemopreventive and chemotherapeutic compound against human breast carcinoma. Tiazofurin (TR), an oncolytic C-nucleoside, inhibits IMP dehydrogenase activity, decreases cellular GTP pools, and downregulates ras gene expression. MDA-MB-435 cells are estrogen receptor negative human breast carcinoma cells that have elevated signal transduction activity. Because TR and TAM decrease signal transduction enzyme activity and inositol 1,4,5-trisphosphate (IP3) concentration via different mechanisms, we tested the hypothesis that the two compounds may be synergistic in human breast carcinoma cells. In MDA-MB-435 cells in growth inhibition assay, the IC50s for TR and TAM were (mean +/- SE) 17 +/- 1.2 and 12 +/- 1.1 microM; in clonogenic assays they were 4 +/- 0.3 and 0.7 +/- 0.3 microM, respectively. When TR was added to MDA-MB-435 cells, followed 12 h later by TAM, synergism was observed in growth inhibition and clonogenic assays and in the reduction of IP3 concentration. The latter may explain, at least in part, the synergistic action of TR and TAM in these cells. The synergistic action of TR and TAM may have implication in the clinical treatment of human breast carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Increased uridine kinase (ATP: uridine 5'-phosphotransferase; EC 2.7.1.48) activity in human and rat tumors.

The activity of uridine kinase (ATP: uridine 5'-phosphotransferase; EC 2.7.1.48), the rate-limiting enzyme of the UMP salvage pathway, was measured in human ovaries and ovarian carcinomas, in a spectrum of six rat hepatomas of different growth rates and in eleven normal rat tissues of high and low cell renewal rates. In a standard isotopic method developed for the 100,000 x g fraction, uridine kinase activity was linear for 20 min and proportional with protein concentration over a range of 0.1 to 0.8 mg per 0.1 ml reaction mixture. The apparent Kms for uridine, ATP and Mg++ in normal rat liver were 5.0, 3.4 and 1.5 mM and in the rapidly growing hepatoma 3924A, 0.8, 2.1 and 1.1 mM, respectively. In normal control ACl/N and Buffalo strain rat livers, kinase activity ranged from 159 to 180 nmol/h/mg protein. In hepatomas of slow and intermediate growth rates, kinase activity increased to 1.5- to 2.6-fold, and in hepatomas of rapid growth rates, to 5.1- to 5.8-fold over that of the relevant control, normal livers. When hepatoma 3924A tissue culture cells were plated and expressed their proliferative program, kinase activity increased to 2.1-fold in early log phase. To further clarify the linkage between uridine kinase and cell replicating capacity, the enzyme activity was measured in rat organs of high and low cell renewal. The kinase activity in liver of adult male Wistar rats was 176 +/- 6 nmol/h/mg protein. Activities in thymus, spleen and bone marrow were 4.7-, 2.1-, and 1.8-fold, respectively, of rat liver values; in adipose tissue, the activities were low. The decay rates of uridine kinase were examined in rats injected with a high dose of cycloheximide, which inhibits protein biosynthesis by 90%. The t(1/2) of the kinase in rat bone marrow was 0.64 h, in rat liver longer than 6 h. In human ovary and ovarian carcinoma, the apparent Kms for uridine were 11.5 and 0.5 mM, respectively. In human ovary (n = 3), kinase activity was 38 nmol/hr/mg protein; in ovarian carcinoma (n = 6), the activity increased to 5- to 13-fold over that in ovary. The positive linkage of uridine kinase activity with proliferation and transformation is apparent in human ovarian carcinomas and in rat hepatomas of different growth rates. Therefore, the increased uridine kinase activity should be an interesting target for anticancer chemotherapy.

Animals↗

Zn(II) dependence of the Aeromonas hydrophila AE036 metallo-beta-lactamase activity and stability.

Two Zn2+ binding sites were found in the Aeromonas hydrophila AE036 metallo-beta-lactamase. The affinity of the first binding site for Zn2+ ions is so high that the dissociation constant could not be determined, but it is significantly lower than 20 nM. The mono-Zn2+ form of the enzyme exhibits a maximum activity against its carbapenem substrates. The presence of a Zn2+ ion in the second lower affinity binding site results in a loss of enzymatic activity with a Ki value of 46 microM at pH 6.5. The kinetic analysis is in agreement with a noncompetitive inhibition mechanism. The Zn content of the A. hydrophila enzyme is also strongly pH-dependent. With an external Zn2+ ion concentration of 0.4 microM, occupancy of the higher affinity site by metal ions is lower than 10% at pH 5 and 10. The affinity for the second binding site seems to increase from pH 6 to 7.5. Fluorescence emission and circular dichroism spectra revealed slight conformational changes upon titration of the apoenzyme by Zn2+ ions, resulting in the successive saturation of the first and second binding sites. Differential scanning calorimetry transitions and intrinsic fluorescence emission spectra in the presence of increasing concentrations of urea demonstrate that the catalytic zinc strongly stabilizes the conformation of the enzyme whereas the di-Zn enzyme is even more resistant to thermal and urea denaturation than the mono-Zn enzyme. The Zn2+ dependency of the activity of this metallo-beta-lactamase thus appears to be very different from that of the homologous Bacteroides fragilis enzyme for which the presence of two Zn2+ ions per molecule of protein appears to result in maximum activity.

Aeromonas hydrophila↗

Osseointegration in cortical sheep bone of calcium phosphate implants evaluated by PIXE method and histology.

Osseointegration of porous calcium phosphate ceramics evolves in several stages once implanted. Histologic analysis has often been used to evaluate the mechanism of integration of this material. Histologic parameters can be completed by physical analysis to obtain a semiquantitative evaluation of the osseointegration process. The histologic observation of hydroxyapatite (HA)-ceramic-containing bone sections was associated with proton-induced X-ray emission (PIXE) analysis and the results obtained by both methods were compared. Porous HA-ceramic cylinders were implanted in cortical bone of sheep femurs for periods ranging from 2 to 36 weeks. Thick sections of the implant containing bone were made at the end of the implantation period. A scanning line with two proton impacts 0.5 mm apart was plotted from the edges of cortical bone across the implanted ceramic and the X-rays produced were determined. Calcium, phosphorus, zinc, strontium, and iron contents were measured. Following PIXE analysis, the sections were surface-stained and observed under a light microscope to define the osseointegration index. Two regions of the curves were identified for each element characterizing either the bone tissue or the ceramic. Zinc and strontium present in the bone tissue but absent from the ceramics appeared after the 8th and the 12th implantation weeks, respectively. Iron present in the implant decreased with time, and calcium and phosphorus contents tended to be the same at the end of the implantation period in both curve regions. Histologic observation showed that immature bone invaded the pores of the outer layer of the ceramic as early as 2 weeks after implantation. Ceramics were totally osseointegrated 20 weeks after implantation. Osseointegration was apparently still evolving as judged by the PIXE method when histologic integration was considered complete.

Animals↗

Microamplification of specific chromosome sequences; an improved method for genome analysis.

An improved method was developed for microdissection and cloning of metaphase as well as pachytene chromosomes. The protocol incorporates efficient ligation of chromosomal DNA with linker adaptors, abolishment of microcloning steps and the reduction of micromanipulation. The threshold for amplifying genomic DNA template was in the range of 2-20 femtogram. The amplification products had a size distribution between 200 and 1300 bp (average 500 bp). Using pachytene chromosomes of maize the selectivity for segment-specific libraries can be increased between 10- and 20-fold. The approach described here is being applied to the fine mapping and isolation of genes conveying resistance against plant pathogens.

Chromosomes↗

Construction of a 1.2-Mb sequence-ready contig of chromosome 11q13 encompassing the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized by parathyroid, pancreatic, and anterior pituitary tumors. The MEN1 locus has been previously localized to chromosome 11q13, and a 2-Mb gene-rich region flanked by D11S1883 and D11S449 has been defined. We have pursued studies to facilitate identification of the MEN1 gene by narrowing this critical region to a 900-kb interval between the VRF and D11S1783 loci through melotic mapping. This was achieved by investigating 17 cosmids for microsatellite polymorphisms, which defined two novel polymorphisms at the VRF and A0138 loci, and utilizing these to characterize recombinants in MEN1 families. In addition, we have established a 1200-kb sequence-ready contig consisting of 26 cosmids, eight BACs, and eight PACs that encompass this region. The precise locations for 19 genes and three ESTs within this contig have been determined, and three gene clusters consisting of a centromeric group (VRF, FKBP2, PNG, and PLCB3), a middle group (PYGM, ZFM1, SCG1, SCG2 (which proved to be the MEN1 gene), and PPP2R5B), and a telomeric group (H4B, ANG3, ANG2, ANG1, FON, FAU, NOF, NON, and D11S2196E) were observed. These results represent a valuable transcriptional map of chromosome 11q13 that will help in the search for disease genes in this region.

Chromosome Mapping↗

Molecular cloning of a novel human gene encoding a 63-kDa protein and its sublocalization within the 11q13 locus.

A human cDNA previously isolated by virtue of its ability to complement partially the ultraviolet sensitivity of a xeroderma pigmentosum cell line was further characterized. The transcription unit is expressed as a single 4.0-kb mRNA that encodes a novel 63-kDa cytoplasmic protein, possibly initiating from an internal AUG codon. The gene encoding this protein, named UVRAG, has been extremely well conserved during evolution, implying an important role for this gene product in cell metabolism. The transcribed mRNA is constitutively expressed in a wide variety of human tissues. The protein encoded by this gene is predicted to contain a coiled-coil structure and is likely to be metabolically unstable based on the occurrence of a strong PEST domain. UVRAG was assigned to human chromosome 11 by Southern hybridization to a somatic cell hybrid panel. Fluorescence in situ hybridization coupled with PCR analysis of human/rodent somatic cell hybrids containing segments of human chromosome 11 has localized this gene to a subregion of 11q13 in between the D11S916 and the D11S906 loci. Importantly, this region has been shown to be amplified in a variety of human malignancies, including breast cancer.

Amino Acid Sequence↗

IMP dehydrogenase inhibitor, tiazofurin, induces apoptosis in K562 human erythroleukemia cells.

Tiazofurin, an anticancer drug which inhibits IMP dehydrogenase, decreases cellular GTP concentration, induces differentiation and down-regulates ras and myc oncogene expression, caused apoptosis of K562 cells in a time- and dose-dependent fashion. Apoptotic cells were detected by (1) flow cytometry, (2) electron microscopy, and (3) fluorescence in situ nick translation and confocal microscopy, while the DNA ladder was not detectable. The induced apoptosis was abrogated by guanosine which replenishes GTP pools through the guanosine salvage pathways, while it was enhanced by hypoxanthine, a competitive inhibitor of GPRT. The tiazofurin-mediated apoptosis may therefore be linked with the decrease of GTP and the consequent impairment of specific signal transduction pathways. Tiazofurin induced apoptosis also in lymphoblastic MOLT-4 cells, suggesting that this action is not confined to cells of the myeloid lineage, where the differentiating effects of the drug are more pronounced.

Apoptosis↗

Isolation of rat hepatic peroxisomes by means of immune free flow electrophoresis.

Rat hepatic peroxisomes (PO) were separated from other cell organelles by free flow electrophoresis (FFE) in combination with immunocomplexing PO prior to FFE with an antibody directed against the cytoplasmic aspect of the peroxisomal membrane protein PMP 70. This novel approach is based on a method termed antigen-specific electrophoretic cell separation (ASECS) which was originally introduced for the isolation of human T and B lymphocyte subpopulations by Hansen and Hannig (J. Immunol. Methods 1982, 51, 197-208). We adapted this technique to PO isolation from a crude peroxisomal fraction, streamlining it by the following modifications: (i) The sandwich-technique recommended to further lower a negative surface charge was renounced. (ii) Instead, the pH of the electrophoresis buffer was raised from 7.2 to 8.0, thus minimizing the electrophoretic mobility of the particles immunocomplexed due to the fact that the isoelectric point (pI) of IgG molecules is close to pH 8.0. PO isolated by this modification, referred to as immune free flow electrophoresis (IFFE), are as pure, intact, and structurally well-preserved as are highly purified PO obtained by density gradient centrifugation. The technique is currently applied for the isolation of peroxisomal subpopulations that are difficult to obtain by means of density gradient centrifugation.

Animals↗

Analysis of sections of implanted macroporous calcium phosphate bone substitutes by proton-induced X-emission method and energy-dispersive spectrometry.

The osseointegration of porous calcium phosphate ceramics once implanted evolves in several stages. The mechanism of integration of such material usually is evaluated by histologic analysis. The trace elements present in bone can be detected in the ceramic and help to provide a semiquantitative evaluation of osseointegration. Two different methods of microanalysis, energy-dispersive spectrometry (EDS) and proton induced x-emission (PIXE) were used in this study to determine the appearance of trace elements (Zn, Sr, and Fe) present in bone at the implantation site containing the ceramic. Porous HA-ceramic cylinders were implanted in the cortical bone of sheep femurs for periods ranging from 2 to 36 weeks. Thick sections of the implant-containing bone were made at the end of the implantation period. A scanning line with proton or electron impacts 0.5 mm apart was plotted from the edges of the cortical bone across the implanted ceramic and the resulting x-ray spectra were determined. Following EDS analysis, the sections were surface-stained, observed under a light microscope, and the pore volume occupied by bone tissue was measured. The spectra obtained by PIXE method showed two regions for each element characterising either the bone tissue or the ceramic. Zinc and strontium present in the bone tissue, but absent from the ceramic, appeared 8 and 12 weeks after implantation, respectively. The concentration of iron present in the implant decreased with time. EDS showed no significant level of either element in the bone or the ceramic. Histologic observation revealed that immature bone invaded the pores of the outer layer of the ceramic as early as 2 weeks after implantation. The ceramics were totally osseointegrated 20 weeks after implantation, although ceramic degradation continued for longer. In this experiment, the PIXE method was apparently sufficiently sensitive for monitoring the amount of trace element appearing in bone-implanted material.

Animals↗