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991.
Elif I. Ekinci Elizabeth L.M. Barr Federica Barzi Jaquelyne T. Hughes Paul D. Lawton Graham R.D. Jones Wendy Hoy Alan Cass Mark Thomas Ashim Sinha George Jerums Kerin ODea Richard J. MacIsaac Louise J. Maple-Brown 《Journal of diabetes and its complications》2019,33(5):343-349
Background
Glomerular hyperfiltration is not able to be detected in clinical practice. We assessed whether hyperfiltration is associated with albuminuria progression among Indigenous Australians at high risk of diabetes and kidney disease to determine its role in kidney disease progression.Methods
Longitudinal observational study of Indigenous Australians aged ≥18?years recruited from >20 sites, across diabetes and/or kidney function strata. At baseline, iohexol clearance was used to measure glomerular filtration rate (mGFR) and hyperfiltration was defined as (i) a mGFR of ≥125?mL/min/1.73?m2, and (ii) an age-adjusted definition, with the top 10% of the mGFR for each 10?year age group at baseline. Baseline and follow-up urine albumin-to-creatinine ratio (uACR) was collected, and linear regression was used to assess the associations of hyperfiltration and uACR at follow up.Results
407 individuals (33% men, mean age 47?years) were followed-up for a median of 3?years. At baseline, 234 had normoalbuminuria and 173 had albuminuria. Among participants with normoalbuminuria, those with mGFR ≥125?mL/min/1.73?m2 had 32% higher uACR at follow-up (p?=?0.08), and those with age-adjusted hyperfiltration had 60% higher uACR (p?=?0.037) compared to those who had normofiltration. These associations were independent of uACR at baseline, but attenuated by HbA1c. Associations were stronger among those without than those with albuminuria at baseline.Conclusions
Although not available for assessment in current clinical practice, hyperfiltration may represent a marker of subsequent albuminuria progression among individuals who have not yet developed albuminuria. 相似文献992.
R M Prewitt C Hoy A Kong S A Gu D Greenberg R Cook S M Chan J Ducas 《The American review of respiratory disease》1990,141(2):290-295
We compared thrombolytic and pulmonary hemodynamic effects of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) in canine micropulmonary thromboembolism. Dogs were embolized with radioactive autologous blood clot to increase mean pulmonary artery pressure (from 13 to 34 mm Hg, p less than 0.005) and decrease cardiac output (2.5 to 1.6 L min, p less than 0.005). Four groups of six dogs were treated. We employed two doses of UK, 30,000 U/kg (UK30) and 60,000 U/kg (UK60), and two doses of rtPA, 1 mg/kg (rtPA1) and 2 mg/kg (rtPA2). Drugs were infused over 15 min. Rate and extent of pulmonary thrombolysis were assessed by continuously counting over both lung fields with a gamma camera. Compared with treatment with UK, both rtPA regimes significantly increased thrombolysis. Mean total pulmonary thrombolysis was 14 and 23% with UK30 and UK60, respectively, and 35 and 43% with rtPA1 and rtPA2. Corresponding to the increased thrombolysis, pulmonary hemodynamics improved most with rtPA. From 90 min to 3 h, pulmonary artery pressure was significantly lower with both rtPA regimes than with either UK regime. These results indicate, at least in the model employed, that compared with treatment with UK, pulmonary thrombolysis and corresponding hemodynamic improvement are greatest with rtPA. 相似文献
993.
Cellular requirements for iron during DNA synthesis are related to the increased activity of the iron-containing M2 subunit of ribonucleotide reductase, the enzyme responsible for the reduction of ribonucleotides to deoxyribonucleotides. We have previously shown that transferrin- gallium (Tf-Ga) inhibits cellular iron incorporation. In the present study, Tf-Ga-induced inhibition of HL60 cell growth and upregulation of Tf receptor density was reversed with hemin. Cells exposed to 2 mumol/L Tf-Ga for six hours or longer displayed a diminution in the electron spin resonance (ESR) spectroscopy signal of the tyrosyl radical of the M2 subunit of ribonucleotide reductase. The effect of Tf-Ga on the ESR signal was reversed by hemin. Tf-Ga decreased the incorporation of 14C- adenosine into DNA and decreased intracellular deoxyribonucleotide pools, with the maximum diminution seen in deoxyadenosine triphosphate (dATP) and deoxycytidine triphosphate (dCTP) pools. Exposure of cells to combinations of Tf-Ga and hydroxyurea (a known inhibitor of ribonucleotide reductase) resulted in a marked inhibition of cell growth that was consistent with drug synergy. Our studies suggest that Tf-Ga inhibits DNA synthesis through action on the M2 subunit of ribonucleotide reductase and that combinations of Ga and hydroxyurea should be further evaluated in in vivo tumor models. 相似文献
994.
David L. Duffy Stephen P. McDonald Beverley Hayhurst Sianna Panagiotopoulos Trudy J. Smith Xing L. Wang David E. Wilcken Natalia L. Duarte John Mathews Wendy E. Hoy 《BMC nephrology》2016,17(1):183
Background
Aboriginal Australians are at high risk of cardiovascular, metabolic and renal diseases, resulting in a marked reduction in life expectancy when compared to the rest of the Australian population. This is partly due to recognized environmental and lifestyle risk factors, but a contribution of genetic susceptibility is also likely.Methods
Using results from a comprehensive survey of one community (N?=?1350 examined individuals), we have tested for familial aggregation of plasma glucose, arterial blood pressure, albuminuria (measured as urinary albumin to creatinine ratio, UACR) and estimated glomerular filtration rate (eGFR), and quantified the contribution of variation at four candidate genes (ACE; TP53; ENOS3; MTHFR).Results
In the subsample of 357 individuals with complete genotype and phenotype data we showed that both UACR (h2?=?64%) and blood pressure (sBP h2?=?29%, dBP, h2?=?11%) were significantly heritable. The ACE insertion-deletion (P?=?0.0009) and TP53 codon72 polymorphisms (P?=?0.003) together contributed approximately 15% of the total heritability of UACR, with an effect of ACE genotype on BP also clearly evident.Conclusions
While the effects of the ACE insertion-deletion on risk of renal disease (especially in the setting of diabetes) are well recognized, this is only the second study to implicate p53 genotype as a risk factor for albuminuria - the other being an earlier study we performed in a different Aboriginal community (McDonald et al., J Am Soc Nephrol 13: 677-83, 2002). We conclude that there are significant genetic contributions to the high prevalence of chronic diseases observed in this population.995.
Clinical relevance of BCL-2 overexpression in childhood acute lymphoblastic leukemia 总被引:9,自引:3,他引:9
Coustan-Smith E; Kitanaka A; Pui CH; McNinch L; Evans WE; Raimondi SC; Behm FG; Arico M; Campana D 《Blood》1996,87(3):1140-1146
Enforced BCL-2 gene expression in leukemic cell lines suppresses apoptosis and confers resistance to anticancer drugs, but the clinical significance of increased BCL-2 protein levels in acute lymphoblastic leukemia (ALL) is unknown. Among 52 children with newly diagnosed ALL, BCL-2 expression in leukemic lymphoblasts ranged widely, from 4,464 to 59,753 molecules of equivalent soluble fluorochrome per cell (MESF), as determined by flow cytometry. The mean (+/- SD) level of MESF in 43 cases of B-lineage ALL (19,410 +/- 11,834) was higher than that detected in CD10+ B-lymphoid progenitors from normal bone marrow (450 +/- 314; P < .001), and CD19+ peripheral blood B lymphocytes (7,617 +/- 1,731; P = .02). Levels of BCL-2 in T-ALL cases (17,909 +/- 18,691) were also generally higher than those found in normal CD1a+ thymocytes (1,762 +/- 670), or in peripheral blood T lymphocytes (9,687 +/- 3,019). Although higher levels of BCL-2 corresponded to higher leukemic cell recoveries after culture in serum-free medium, they did not correlate with higher cell recoveries after culture on stromal layers, or with in vitro resistance to vincristine, dexamethasone, 6- thioguanine, cytarabine, teniposide, daunorubicin or methotrexate. BCL- 2 protein levels did not correlate with presenting clinical features. Unexpectedly, however, lower-than-median MESF values were significantly associated with the presence of chromosomal translocations (P = .010). Notably, all six cases with the Philadelphia chromosome, a known high- risk feature, had low levels of BCL-2 expression (P = .022). Higher levels of BCL-2 were not associated with poorer responses to therapy among 33 uniformly treated patients, and were not observed in three patients studied at relapse. In conclusion, increased BCL-2 expression in childhood ALL appears to enhance the ability of lymphoblasts to survive without essential trophic factors, and is inversely related to the presence of chromosomal translocations. However, it does not reflect increased disease aggressiveness or resistance to chemotherapy. 相似文献
996.
997.
Occurrence of Norwalk virus infections among adults in Mexico 总被引:3,自引:0,他引:3
P C Johnson J Hoy J J Mathewson C D Ericsson H L DuPont 《The Journal of infectious diseases》1990,162(2):389-393
Norwalk virus infection was sought in 48 US, 49 Puerto Rican, and 27 Mexican adults attending medical school in Guadalajara (Mexico) who were enrolled in a 2-year longitudinal study. Serum specimens were collected quarterly and as acute- and convalescent-phase samples around episodes of gastroenteritis. The reciprocal Norwalk virus geometric mean titer (GMT) for Puerto Rican students (567) was significantly higher than that of the US students overall (294; P less than .001) and for four of nine quarterly periods. The reciprocal Norwalk GMT for Mexican students (748) was also significantly higher than that of the US students overall (P less than .001) and for seven of nine quarterly periods. The average percentage of students per year with seroconversions was 30%. The rate of Norwalk virus infection averaged 0.36 episodes per student-year. Symptoms of gastroenteritis associated with seroconversion occurred in 45% of students. Preexisting serum antibody did not protect against subsequent Norwalk virus infection in these subjects. All student groups had similar rates of infection and symptomatic gastroenteritis. 相似文献
998.
999.
Effects of B cell stimulatory factor-1/interleukin 4 on hematopoietic progenitor cells 总被引:13,自引:1,他引:13
B cell stimulatory factor-1 (BSF-1)/Interleukin 4 (IL 4) is a T cell product originally characterized on the basis of its actions on B lymphocytes. Recently it has been reported that BSF-1 activates T cell and mast cell lines. We now provide evidence that BSF-1, purified to homogeneity, also has a broad spectrum of activity on hematopoietic progenitor cells (HPC). However, like its action on B cells, prolierative effects were only observed when BSF-1 was combined with an additional factor. Thus BSF-1, in costimulation with recombinant G-CSF, enhances the proliferation of granulocyte-macrophage progenitor cells (CFU-GM). BSF-1 increases the proliferation of CFU-e in the presence of recombinant erythropoietin (rEPO). Furthermore, BSF-1 induces, together with rEPO, colony formation by primitive erythroid (BFU-e) and multipotent (CFU-mix) progenitor cells comparable to that observed with rEPO and interleukin 3 (IL 3). BSF-1 is also active as a megakaryocyte colony-stimulating factor; in combination with recombinant interleukin 1, rEPO or the supernatant of the T cell hybridoma FS7-20.6.18, BSF-1 induces megakaryocyte colony formation (CFU-Mk). The same factors that synergize with BSF-1 also enhance CFU-Mk proliferation induced by IL 3. Although the precise mechanisms of action of BSF-1 on HPC is not yet known, we propose that BSF-1 represents an activation factor for HPC and prepares the progenitor cells to respond to specific growth or differentiation factors. 相似文献
1000.