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Biomedical subjects

C Jacobs

Publications and source records attributed to C Jacobs.

At least 91 records · Page 5Linked to original sources
PubMed1999

Does early anemia correction prevent complications of chronic renal failure?

Anemia is a common complication of chronic renal failure (CRF). With the availability of recombinant human erythropoietin (rhEPO) over the last decade, much progress has been made in the management of anemia in patients with end-stage renal disease (ESRD) [Eschbach 1995, Gimenez and Scheel 1994, Muirhead et al. 1995, Winearls 1995]. The clearest benefit of rhEPO in ESRD is a substantial reduction in transfusion dependency, which reduces the need for hospital admission and the risk of viral transmission. Improvements in hemostasis and a decrease in human leucocyte antigen (HLA) antibodies have also been reported. Beneficial effects of rhEPO on the cardiovascular system in ESRD include regression of left ventricular hypertrophy (LVH), improvement of angina, and a modest increase in aerobic work capacity. Treatment of anemia with rhEPO has also been shown to improve cognitive function, socialization and quality of life in dialysis patients, although this has not led to better vocational rehabilitation or employment status. It has also been reported that a lower hemoglobin (Hb) content is an independent risk factor for increased mortality in hemodialysis patients [Harnett et al. 1995]. Clearly, therefore, treatment of anemia associated with ESRD is required and beneficial. The optimum treatment of anemia prior to dialysis, however, is still a matter for debate.

Anemia↗
PubMed1998

LPS-induced cytokine production and expression of beta2-integrins and CD14 by peripheral blood mononuclear cells of patients with homozygous familial hypercholesterolemia.

It has been suggested that proinflammatory cytokines such as tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1), as well as adhesion molecules such as beta2-integrins and CD14, play a role in the pathogenesis of atherosclerosis. Familial hypercholesterolemia (FH) is an autosomal disease in which defective or absent LDL receptors are the cause for extreme LDL concentrations and early development of atherosclerosis. We studied lipopolysaccharide-induced cytokine production and the expression of adhesion molecules by mononuclear cells of three homozygous FH patients and compared them with first-degree relatives and healthy controls. There was a tendency towards increased cytokine production by cells of FH patients, whereas the expression of adhesion molecules was not modified compared to controls. In addition, LDL-apheresis inhibited IL-1 and TNF production and the expression of CD11a, CD11b, CD11c and CD14 by the mononuclear cells of FH patients and this may be an additional beneficial effect of LDL-apheresis apart of decreasing LDL concentrations.

Adolescent↗
PubMed1998

Microbial asymmetric cell division: localization of cell fate determinants.

The genetic mechanisms that control asymmetric cell divisions--yielding progeny cells that differ from one another--have been conserved among prokaryotes, eukaryotic microbes, and higher organisms. All use the paradigm of regulatory protein localization as a way of translating genetic information into three-dimensional space.

Animals↗
PubMed1998

Kidney transplants from living donors: how donation affects family dynamics.

Living donors continue to provide the optimum outcome for kidney transplant recipients, yet information is limited on how donation can affect the donor and his or her family. Questionnaires returned by 524 donors whose donor nephrectomies took place between August 1, 1985 and December 31, 1996 at the University of Minnesota were analyzed to determine if perioperative complications influence their quality of life, among other emotional and lifestyle areas. Results showed that donors have a higher quality of life than the general population, confirming they have an increased self-worth and positive self-esteem. An overwhelming 96% would donate again. However, donation was self-reported as more stressful when complications were experienced (P = .003) and when donors were female (P = .041). Relatives other than immediate family members (extended relatives) were more likely to be among the 4% who said they would not donate again. Available support, financial impact, and relationship changes as a result of donation also were revealed. Relevant results from this larger study are discussed as they relate to how the renal donor and transplant family are affected.

Adolescent↗
PubMed1998

Is ionic dialysance a valid parameter for quantification of dialysis efficiency?

The on-line measurement during hemodialysis of ionic dialysance provides an estimation of urea clearance with a good and already proven correlation. Some discrepancies remain controversial, and the influence of the dialyzer membrane is still being debated. Eighty-eight measurements of ionic dialysance (ID) were performed with a Diascan module (Hospal R&D, Int., Lyon, France), 51 with cellulosic membranes, and 37 with synthetic membranes, chosen according to their surface charges. The ID was compared to the urea clearance (UK) measured from the blood (n=16) and dialysate (n=88) sides. The ID is closely correlated (r=0.91) but significantly (p < 0.01) lower than the UK by 5% (ID/UK=0.95+/-0.06). The correlation is improved by a semilogarithmic regression analysis (r=0.93). Regarding the influence of the membrane charge, a slight difference is only evidenced for UK < 180 ml/min whereby ID is closer to the urea clearance for the charged membranes (ID/UK=0.98+/-0.05 for charged membranes versus 0.95+/-0.05 for noncharged membranes, p < 0.05). The discrepancy between ID and UK could be related with the difference in the blood distribution volume of urea and that of electrolytes. The good correlation provides the major argument for ID being used as a monitoring parameter of the delivered dialysis dose. Having integrated the discrepancy between ID and UK, prescription can be guided by ID for delivering the adequate normalized dialysis dose as defined by Kt/V.

Hemodialysis Solutions↗
PubMed1997

A prospective randomized trial of buffy coat versus CD34-selected autologous bone marrow support in high-risk breast cancer patients receiving high-dose chemotherapy.

High-dose chemotherapy with hematopoietic progenitor cell support is administered increasingly to selected categories of patients with high-risk malignancies. Bone marrow and/or peripheral blood progenitor cells (PBPCs) are commonly cryopreserved with the cryoprotectant dimethyl sulfoxide (DMSO), which can cause a variety of systemic side effects when the graft is thawed and infused. The progenitor cells thought to be responsible for hematopoietic recovery express the CD34 antigen and constitute 1% to 3% of the marrow cells and 0.5% of the PBPC fraction. Transplantation of a CD34(+) graft would markedly reduce the volume and thus the amount of DMSO required, thereby decreasing the infusion-related toxicities. In this study, 89 high-risk breast cancer patients received high-dose therapy and were randomized to receive an autologous CD34(+) marrow graft (Arm A) versus a standard buffy coat fraction (Arm B). After marrow infusion, significant increases in diastolic and systolic blood pressure, as well as significant decreases in heart rate, were documented in Arm B compared to Arm A patients (P < .001). None of the patients in Arm A experienced any clinically serious adverse events associated with the marrow infusion compared to 6% of the Arm B patients. The median time to neutrophil engraftment was 13 days for Arm A and 11 days for Arm B patients (P = .218). The median time to platelet engraftment was 27 days for Arm A and 20 days for Arm B patients (0.051). There were no other significant differences between the two arms of the study with respect to thrombocytopenia-related complications or immune function reconstitution. Additionally, patients on Arm A who received >/=1.2 x 10(6) CD34(+) cells/kg had no delay in platelet recovery (22 days), compared to patients on Arm B, who also received greater than 1.2 x 10(6) CD34(+) cells/kg (20 days) (P = .604). In conclusion, this prospective randomized study demonstrates that breast cancer patients who receive high-dose therapy with autologous CD34(+) marrow support have reduced marrow infusion-related toxicity, comparable time to neutrophil engraftment and immune function recovery posttransplant, and for those who receive <1.2 x 10(6) CD34(+) cells/kg, comparable time to platelet engraftment compared to women who receive buffy coat fractions of marrow.

Adult↗
PubMed1997

Cytosolic intermediates for cell wall biosynthesis and degradation control inducible beta-lactam resistance in gram-negative bacteria.

beta-lactam induction of chromosomal beta-lactamase in gram-negative bacteria requires the transcriptional regulator AmpR and the transport of murein breakdown products (muropeptides) into the cytoplasm. In vitro transcription shows that purified AmpR acts as an activator for ampC beta-lactamase synthesis. The murein precursor, UDP-MurNAc-pentapeptide, decreases AmpR-mediated transcriptional activation in vitro, but has no effect on an AmpR(G102E) mutant that mediates constitutive activation of ampC in vivo. Addition of the muropeptide, anhMurNAc-tripeptide, which accumulates in beta-lactamase-overproducing mutants, counteracts the negative effect of UDP-MurNAc-pentapeptide, restoring the innate ability of AmpR to induce ampC expression in vitro. Cytosolic intermediates of murein biosynthesis and degradation thus act antagonistically to control beta-lactamase expression, thereby operating as a cell-wall sensing device.

Bacterial Proteins↗
PubMed1997

Activation of p53 transcriptional activity by 1,10-phenanthroline, a metal chelator and redox sensitive compound.

p53, a tumor suppressor gene, functioning as a transcription factor, has been recently shown in a cell free system to be subject to redox (reduction/oxidation) regulation. Oxidants or metal chelating reagents disrupt wildtype p53 conformation and decrease or abolish its DNA binding activity, while reductants restore wildtype conformation and increase DNA binding. We have extended these observations to intact cell systems by using luciferase transactivation assay in two murine tumor cell lines, both harboring endogenous wildtype p53. The results showed that none of these in vitro active reagents, except 1,10-phenanthroline (OP) has a significant effect on p53 transactivation activity. OP, a metal chelator and p53 inactivator in cell free systems, however, induces p53 transactivation activity as well as sequence-specific DNA binding in a dose dependent manner. OP also differentially induces endogenous expression of several known p53 target genes such as Waf-1 and Mdm-2, but not Bax, Gadd45, and PCNA. Increased p53 activity induced by OP is not due to elevated p53 mRNA nor to protein levels. Furthermore, the OP-induced p53 transcriptional activation is not due to its potential DNA intercalating activity, but mainly due to its metal chelating activity. OP was also found to induce dramatically apoptotic cell death in these tumor cells harboring wildtype p53, to a less extent in MEF cells from p53 knockout mice and not at all in Saos-2 cells without p53 or Rb. We concluded from this study that (a) unlike what has been seen in vitro, OP induces p53 activity in intact cells (b) OP activates p53 transcriptional activity without increasing p53 protein; and (c) activation of p53 may contribute to apoptosis, but is not required.

Animals↗
PubMed1997

Neoadjuvant therapy for surgically staged IIIA N2 non-small cell lung cancer (NSCLC).

INTRODUCTION: Neoadjuvant therapy in patients with Stage IIIA NSCLC is associated with a 50-70% resection rate and a 3-5 year survival of 20-32%, but few trials have required meticulous staging of the mediastinum to ensure homogeneity of the study population. Continuous infusion cisplatin 25 mg/m2/day 1-5, 5-fluorouracil 800 mg/m2/day 2-5, and high-dose leukovorin 500 mg/m2/day 1-5 (PFL) given every 4 weeks achieved a 41% response rate in metastatic NSCLC (Lynch TJ, Kalish LA, Kass F, Strauss G, Elias A, Skarin A, Shulman L, Sugarbaker D, Frei E. Continuous infusion cisplatin, 5-fluorouracil, and leukovorin for advanced non-small cell lung cancer. Cancer 1994; 73: 1171-1176). The regimen was therefore evaluated in 34 patients with pathologic Stage IIIA N2 disease between 3/91 and 10/92. METHODS: Staging consisted of chest, liver, brain computerized tomography and bone scan, bronchoscopy and surgical mediastinal node mapping. Patients received PFL for 3 cycles, followed by thoracotomy and thoracic radiotherapy (TRT) to 54-60 Gy. RESULTS: Median age was 57 (42-68) years. Demographic factors included: male 56%; adenocarcinoma 59%, squamous cell carcinoma 24%; Stage T3N2 26%, T2N2 56%, and T1N2 18%. No treatment related deaths occurred. Radiographically defined response to PFL was 65% (6% complete). Thoracotomy was performed in 28 patients (82%) (6 had no attempt due to disease progression). Complete resection was achieved in 21 (75%) and seven were unresectable. Pathologic complete response was observed in five patients (15%) and an additional unresectable patient had fibrosis-only documented at thoracotomy for an overall clinicopathologic response rate of 76% (18% pathologic CR). Another ten patients had residual primary with or without hilar disease with resolution of previously documented mediastinal involvement. Six (18%) patients remain alive and disease-free with a median follow-up of 46 (33-50) months, four of whom had achieved pathologic complete response at time of surgery. CONCLUSIONS: Long-term event-free survival was associated with complete surgical resection which in turn was associated with clinical response to chemotherapy. There was a possible trend associating pathologic downstaging (absent residual disease in mediastinal nodes), particularly pathologic complete response observed in patients with non-bulky mediastinal disease, with improved event-free survival. Pathologic downstaging might therefore be a useful surrogate endpoint in trials evaluating the preoperative activity of new chemotherapy regimens. While radiographic response generally correlated with findings at surgery, response as determined by histologic examination of resected tissue was generally more extensive and may more accurately reflect the systemic impact of the chemotherapy regimen.

Adult↗
PubMed1997

Role of endothelium-derived nitric oxide-endothelin balance in contrast medium-induced acute renal vasoconstriction in dogs.

RATIONALE AND OBJECTIVES: The authors evaluated the involvement of nitric oxide and endothelin in radiographic contrast medium-induced changes in renal hemodynamics. METHODS: Eleven anesthetized healthy dogs were each studied during three periods. Thirty minutes before the first, second, and third periods, the dogs received 1 mL per kilogram of body weight of isotonic saline, L-N-nitro-L-arginine-methyl-ester (L-Name, 10 mg/kg intravenously), and L-arginine (500 mg/ kg intravenously), respectively. Renal blood flow (RBF) and mean arterial blood pressure were continuously monitored. The glomerular filtration rate (GFR) was evaluated by means of polyfructosan clearance. RESULTS: Contrast medium induced a significant (P < .05) decrease in RBF and GFR and a significant (P < .05) increase in urinary endothelin excretion. L-Name enhanced the effect of contrast media on RBF and GFR. L-arginine attenuated the effect of L-Name on the contrast medium-induced reduction of GFR. CONCLUSION: These findings support the hypothesis that acute contrast medium-induced intrarenal vasoconstriction may involve an imbalance of endothelial vasoactive agents, nitric oxide, and endothelin, and they confirm the involvement of hemodynamic changes in contrast medium-induced nephropathy.

Animals↗