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Biomedical subjects

D Baran

Publications and source records attributed to D Baran.

At least 37 records · Page 2Linked to original sources

Correlation of bone mineral density and femoral neck hardness in bovine and human samples.

Bone mineral density (BMD) is a predictor of fracture risk. The purpose of this study was to determine whether a correlation exists between femoral neck BMD and an indicator of mechanical bone strength in human and bovine samples. Human proximal femurs were obtained from seven men and two women undergoing total hip arthroplasty (THA), mean age 60.3 years. Preoperative BMD measurements of the femoral neck were obtained (Lunar DPX). A 3 cm2 area of interest on each excised femoral neck corresponding to the preoperative BMD measurement site was carefully marked and BMD was remeasured postoperatively. Ten excised bovine femoral necks were also measured for BMD. A bicortical core, each cortex 2.8 cm2 in area, containing the center of the area of interest was removed from the human and bovine femoral necks, cut into multiple 7-mm thick, multiple cross-sectional discs, and measured for hardness by indent depth (Rockwell International Hardness Tester, Wilson Mechanical Instruments, New York, NY). In vivo human femoral neck BMD measurements correlated with in vitro BMD measurements (r = 0.99). BMD measurements of human femoral necks were significantly lower than BMD measurements of bovine femoral necks (P < 0.05). Inverse relationships were found between in vivo and in vitro human BMD measurements and indent depth (r = -0.58 and -0.59, respectively). Bovine BMD measurements and indent depth were also inversely related (r = -0.64).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of vitamin D3 and cyclosporin A on HgCl2-induced autoimmunity in brown Norway rats.

BACKGROUND: Mercuric chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway (BN) rats. This syndrome is the consequence of T cell-dependent polyclonal B cell activation and autoantibody production. We have previously shown that HgCl2-induced autoimmune perturbations can be prevented in BN rats by the administration of cyclosporin A (CsA). The most potent vitamin D3 metabolite 1,25(OH)2 D3 (Vit D3) shares certain immunomodulatory properties with CsA. We therefore chose to compare the effects of Vit D3 to those of CsA in BN rats treated with HgCl2 in order to establish whether Vit D3 either alone or in combination with CsA can attenuate an autoimmune syndrome in vivo. METHODS: BN rats were treated with HgCl2 according to a standard protocol. Subgroups of rats were also given CsA alone, Vit D3 or synthetic analogues of Vit D3 alone, or combinations of both agents. Different doses and routes of administration were compared. The following markers of disease activity were evaluated: mortality, peak proteinuria, serum IgE concentrations, and renal immunoglobulin deposition. RESULTS: Disease activity was markedly attenuated in all rats treated with CsA alone. Vit D3 and certain of its synthetic analogues administered alone also tempered the autoimmune process, but to a lesser extent than did CsA. The effect of CsA alone was so potent, that no additive or synergistic effects could be demonstrated when CsA was administered in combination with Vit D3. CONCLUSIONS: Despite similar described immunomodulatory effects in vitro, CsA is clearly more effective than Vit D3 in preventing HgCl2 autoimmune disease in BN rats. This suggests that there is a difference in the cellular targets of these two agents in vivo, and/or a difference in the potency with which HgCl2-triggered immune activation is suppressed.

Animals↗

Genome macrorestriction analysis of diversity and variability of Pseudomonas aeruginosa strains infecting cystic fibrosis patients.

Genome macrorestriction fingerprinting with XbaI and DraI was used to analyze the relatedness of 166 Pseudomonas aeruginosa isolates collected from 31 cystic fibrosis patients over a 1- to 20-month period and to correlate their genotype with patterns of resistance to 14 antimicrobial agents. Quantitative comparison of intra- and interpatient similarities of P. aeruginosa macrorestriction patterns disclosed two discrete ranges that clearly discriminated subclonal variation (> 80% relatedness) and clonal diversity (10 to 70% relatedness). Cloning-derived mutants exhibited up to 20% divergence of genomic macrorestriction patterns during the course of chronic colonization of individual patients. Change of susceptibility to multiple antimicrobial agents developed in 50% of sequential pairs of isolates from individual patients. Only 19% of these susceptibility changes were attributable to strain substitution, while the majority (56%) of resistance changes were associated with minor genomic variations of a persistent strain. Sixty-six percent of patients harbored one strain, and 33% carried two strains. Three common strains colonized 5 (28%) of 18 patients attending a cystic fibrosis clinic, and another two strains colonized two patient pairs (31%) of 13 patients staying at a rehabilitation center, suggesting potential cross-infection in these settings. By indexing regional polymorphisms throughout the chromosome structure, macrorestriction analysis can monitor subclonal evolution of P. aeruginosa and identify isogenic resistance mutants. Quantitative macrorestriction fingerprinting enables discrimination between clonal variants and clones of distinct origins and should therefore provide a reliable tool for investigating the mode of acquisition of P. aeruginosa in cystic fibrosis patients.

Cross Infection↗

Ultrasound attenuation of the calcaneus: a sensitive and specific discriminator of osteopenia in postmenopausal women.

Recent studies have evaluated techniques for estimating bone mass without radiation. The present study compares broadband ultrasound attenuation of the calcaneus and bone densities of the femoral neck and the lumbar spine in 17 normal women and 41 women with osteoporosis. Twenty of the osteoporotic women had spine (n = 16) or femoral neck (n = 4) fractures. There was a significant decrease in the broadband ultrasound attenuation (P less than 0.001) in women with osteoporosis compared with normal women. The osteoporotic women also showed a decrease in vertebral (P less than 0.0001) and femoral neck (P less than 0.0001) densities compared with normal women. At 63 dB/MHz, the sensitivity and specificity of broadband ultrasound attenuation for decreased bone mineral density with or without fractures were 76%. All women with fractures had a broadband ultrasound attenuation less than 72 dB/MHz. This corresponded to a specificity of 41%. To determine whether broadband ultrasound attenuation correlated with trabecular bone volume, samples of cadaver calcaneus were analyzed. The histologic determination showed a significant correlation between broadband ultrasound attenuation and trabecular bone volume (r = 0.992, P = 0.008). These results suggest broadband ultrasound attenuation of the calcaneus reflects bone mass and can be used as a safe and sensitive indicator for decreased axial bone density.

Absorptiometry, Photon↗

Concentration of tobramycin given by aerosol in the fluid obtained by bronchoalveolar lavage.

Whereas previous studies have used only bronchial secretions and sputum, in the present study, bronchoalveolar (BAL) fluid was analysed for tobramycin levels after aerosolization of this antibiotic. In 20 adult patients with a variety of lung disorders, the concentration of tobramycin obtained in the first aliquot of the bronchoalveolar fluid varied from less than 0.1 to 9.2 micrograms ml-1 (mean 2 +/- 2.26 micrograms ml-1) with 18 samples above 0.4 micrograms ml-1. In most of the cases, the concentration of tobramycin achieved values of tobramycin in excess of the minimal inhibitory concentration for most of the microorganisms. Thus, sampling fluids by the bronchoalveolar technique offers a suitable method to study antibiotic levels at the site of broncho-pulmonary infection. These results may help explain why aerosol antibiotic treatment appears to be useful in selected patients, especially in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa.

Administration, Intranasal↗

Dietary modification with dairy products for preventing vertebral bone loss in premenopausal women: a three-year prospective study.

The effect of dietary calcium on vertebral bone mass in women is controversial. In a randomized study we have investigated the effect of dietary modification in the form of dairy products on vertebral bone mass in 30- to 42-yr-old premenopausal women over a 3-yr period. Twenty women increased their dietary calcium intake by an average of 610 mg/day (P less than 0.03) for 3 yr, while 17 age- and weight-matched women served as controls. Calcium intake was monitored by 3-day diet histories and 24-h urinary calcium excretion. The consumption of the dairy products did not alter serum calcium or PTH levels or the fasting urinary calcium to creatinine ratio. Twenty-four-hour urinary calcium excretion increased by 28% (P less than 0.03) in the supplemented women. Dairy product intake was accompanied by increased dietary fat intake, but there were no statistically significant changes in serum cholesterol, low density lipoprotein cholesterol, or high density lipoprotein cholesterol levels. The vertebral bone density in the women consuming increased calcium did not change over the 3-yr period (-0.4 +/- 0.9%). In contrast, the vertebral bone density in the control women declined (-2.9 +/- 0.8%; P less than 0.001) and was significantly lower than that in the supplemented group at 30 and 36 months. The study suggests that dietary modification in the form of dairy products retards vertebral bone loss in premenopausal women. Therefore, increased calcium intake in estrogen-replete premenopausal women may prevent age-related bone loss.

Adult↗

Activation by IL-2, but not IL-4, up-regulates the expression of the p55 subunit of the IL-2 receptor on IL-2- and IL-4-dependent T cell lines.

We have investigated the effects of IL-2 and IL-4 on different parameters of T cell activation using three T cell lines. The Th cell line L14 and the cytotoxic T cell line C30.1, both grown in IL-2-containing medium, and a line derived from C30.1 cells (line 1) cultured in IL-4 for a prolonged period were studied. All three cell lines could be activated with IL-2 or IL-4. T cell stimulation by either IL-2- or IL-4-induced identical patterns of cell size enlargement and transferrin receptor expression. However, only IL-2 up-regulated cell-surface expression of the p55 subunit of the IL-2R (p55 IL-2R) as measured by flow cytometry and RIA. This difference was also reflected by the accumulation of soluble p55 IL-2R in the culture medium. No significant increase in expression of membrane or soluble forms of p55 IL-2R was detected after IL-4 stimulation. mAb specific for p55 IL-2R which block IL-2-induced T cell growth did not affect IL-4-mediated T cell proliferation indicating that p55 IL-2R is not involved in IL-4-mediated T cell growth. Analysis of IL-4R expression performed on line 1 using biotinylated IL-4 revealed that IL-4, but not IL-2, is capable of increasing IL-4R expression. Together these results suggest that during IL-2- or IL-4-induced T cell proliferation, each lymphokine specifically up-regulates its own receptor.

Animals↗

The effect of ovariectomy on spine bone mineral density in rhesus monkeys.

As part of a study on the effects of hormones on uterine biology and estrogen metabolism, 12 normal female rhesus (Macaca mulatta) monkeys were ovariectomized, and treated intermittently with estradiol and progesterone. In order to determine whether there were changes in bone density as a result of ovariectomy despite the hormone therapy, spine bone mineral density (BMD) was measured by dual-photon absorptiometry. The mean +/- SE time from ovariectomy was 26 +/- 3 months, the mean estrogen treatment time was 3.5 +/- 0.4 months and the mean time from last hormonal treatment was 4.1 +/- 0.6 months. In these 12 monkeys aged 7.7 +/- 0.2 years, the mean spine BMD, 0.825 +/- 0.008 g/cm2, was significantly less, p = 0.0011, than the spine BMD, 0.863 +/- 0.007 g/cm2, in 12 intact female rhesus of similar age, 7.6 +/- 0.1 years and weight. Ovariectomy in female rhesus monkeys results in a relatively rapid diminution of spine BMD which is not prevented by intermittent hormonal replacement. This species may be an excellent model for studies of human osteoporosis.

Absorptiometry, Photon↗

[Cervical ectopic thymus].

Two cases of cervical aberrant thymus in infants are reported; it's important to identify such ectopia because thymic tissue involutes spontaneously later on; neither surgery nor other treatment is needed. Ultrasonography is a method of choice for tissue characterization of ectopic thymus and differential diagnosis with other cervical masses.

Diagnosis, Differential↗

Characterization of the soluble murine IL-2R and estimation of its affinity for IL-2.

IL-2 induces cells of the cytotoxic T cell line C30.1 to express large numbers of membrane IL-2R (mIL-2R). At the height of activation, these cells also release a soluble form of IL-2R (sIL-2R). Using either crude supernatant or a semi-purified preparation of sIL-2R obtained by affinity chromatography, studies were performed to characterize murine sIL-2R. Its m.w. was determined by both gel filtration and SDS-PAGE. The affinity of sIL-2R for a panel of mAb known to recognize different epitopes of mIL-2R (p55 subunit) was assessed by saturation and competition experiments. The relationship between the various epitopes was studied by cross-inhibition experiments. The data suggest that sIL-2R and mIL-2R (p55 subunit) are structurally similar. The ability of sIL-2R to bind IL-2 was assessed by measuring the dissociation and the inhibition constant of the molecule for IL-2. Both values coincide and indicate that the affinity of sIL-2R for IL-2 is at least 10-fold lower than the that of low affinity mIL-2R. The biologic implications of these findings are discussed.

Animals↗

Carrier prediction of cystic fibrosis in 36 families by means of restriction fragment length polymorphism.

Transmission of cystic fibrosis (CF) was studied in 36 families with at least one affected and one unaffected child. DNA was prepared from peripheral leukocytes and submitted to restriction fragment length polymorphism (RFLP) analysis with two CF probes (pj3.11 and met). Twenty families were shown to be informative so that accurate predictions could be made of the status of the offspring. Sixteen were only partially informative. The allele frequency was similar to that originally reported except for one Msp I site detected with the pj3.11 probe, for which we found a significantly higher heterozygote frequency, making it more informative than expected in our population sample. Pedigree analysis demonstrated no obligate recombinant between CF and the polymorphic markers.

Cystic Fibrosis↗

Plasma exchange in a rat model of autoimmune glomerulonephritis.

Using an original technique permitting repeated plasma exchange in the rat, we have tested this therapeutic approach in animals actively immunised with horseradish peroxidase, and in rats with HgCl2-induced autoimmune glomerulonephritis. Plasma exchange effectively removes circulating IgG anti-horseradish peroxidase antibodies from the sera of immunised rats. When applied to the model of HgCl2-induced antiglomerular basement membrane glomerulonephritis in Brown-Norway rats, this technique is also remarkably effective. In these rats, proteinuria is abolished during the plasma exchange treatment period and no circulating antiglomerular basement membrane antibodies can be detected. These antibodies are, however, found in the ultrafiltrates of exchanged rats. Serum IgE, characteristically elevated in HgCl2-treated rats, is also markedly diminished in exchanged rats. Control rats treated with infusions of fresh frozen plasma or with heparin alone did not show any improvement in disease severity. These results suggest that plasma exchange alone can attenuate antiglomerular basement membrane nephritis in HgCl2-treated rats. This observation may be of relevance for the treatment of human antiglomerular-basement membrane-mediated glomerulonephritis.

Animals↗

Interleukin-2 production in Brown-Norway rats with HgCl2-induced autoimmune disease: paradoxical in vivo versus in vitro findings.

In autoimmune diseases, mitogen-induced IL-2 production in vitro is generally considered to be diminished despite evidence of lymphoid hyperactivity in vivo. HgCl2 is known to cause T-dependent polyclonal B cell activation in Brown-Norway (BN) rats, resulting in autoimmune disease. We show here that the IL-2 producing capacity of cells from HgCl2-treated BN rats is low, but that HgCl2 treatment in vitro (10(-7) M) enhances IL-2 production of normal BN splenocytes. Lewis (LEW) rats are resistant to HgCl2-induced autoimmune disease. HgCl2 treatment of these rats in vivo does not significantly decrease the IL-2 production of their splenocytes. However, HgCl2 treatment of normal LEW splenocytes in vitro enhances their IL-2 production but this requires an HgCl2 concentration ten times greater (10(-6) M) in LEW than in BN rats. These findings are discussed in an attempt to resolve the paradox between the in vivo immune hyperactivity seen in HgCl2-treated BN rats, and the apparently low IL-2 production of their splenocytes in vitro.

Animals↗

Evidence for negative regulation of T cell growth by low affinity interleukin 2 receptors.

Two experimental situations have been studied, and the results provide evidence for a negative regulatory role for the low affinity interleukin 2 receptor (LA-IL 2R). The IL 2-dependent T helper cell line L-14, deprived of IL 2, becomes quiescent and expresses comparable numbers of high affinity IL 2R (HA-IL 2R) and LA-IL 2R. After activation by recombinant IL 2, this cell line preferentially expresses LA-IL 2R. The IL 2 responsiveness of the L-14 cell line was found to vary according to the ratio of LA-IL 2R to HA-IL 2R: the relative predominance of the LA-IL 2R coincides with a hyporeactivity of cells to IL 2. In contrast, a predominance of HA-IL 2R is accompanied by an increase in cellular IL 2 reactivity. Treatment of three IL 2-dependent T cell lines (L-14, HT-2, and C30.1) with limited amounts of recombinant IL 2 and moderate concentrations of anti-IL 2R monoclonal antibodies stimulates T cell growth. This treatment was shown to selectively diminish the expression of membrane LA-IL 2R. The stimulation was attributed to the decrease of expression of LA-IL 2R.

Animals↗