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Biomedical subjects

A Fine

Publications and source records attributed to A Fine.

At least 37 records · Page 2Linked to original sources
PubMed2000

Analysis of microbiological trends in peritoneal dialysis-related peritonitis from 1991 to 1998.

The microbial cause of peritoneal dialysis-related peritonitis is an important determinant of clinical outcome and the basis of widely used treatment guidelines. Five hundred forty-six cases of peritonitis in 374 patients from 1991 to 1998 were analyzed. The rate of peritonitis declined significantly from 1.37 episodes/patient-year in 1991 to 0.55 episode/patient-year in 1998 (P = 0.02). The rate of Gram-positive peritonitis decreased significantly from 0.75 to 0.28 episode/patient-year during the same period (P = 0.02). Conversely, the occurrence of Gram-negative peritonitis remained constant at approximately 0.16 episode/patient-year (P = 0.28). Staphylococcus epidermidis and Staphylococcus aureus were the most common causes of peritonitis, isolated in 27.8% and 19.3% of the culture-positive cases, respectively. A distinct decrease in peritonitis caused by S epidermidis was observed, with 0.40 episode/patient-year in 1991 compared with 0.11 to 0.20 episode/patient-year during subsequent years. The rate of infections caused by S aureus decreased significantly over time from a high of 0.21 episode/patient-year in 1992 to a low of 0.04 episode/patient-year in 1998 (P = 0.01). Pseudomonas aeruginosa, Escherichia coli, and KLEBSIELLA: species were the most common causes of Gram-negative peritonitis, identified in 7.1%, 6.8%, and 5.2% of culture-positive cases, respectively. The most dramatic increase in antibiotic resistance was seen among S epidermidis. From 1991 and 1992 to 1997 and 1998, resistance to ciprofloxacin increased from 5.4% to 47.8% (P = 0.003), and resistance to methicillin increased from 18.9% to 73.9% (P = 0.03). Our study showed significant trends in the causative pathogens of peritoneal dialysis-related peritonitis and dramatic increases in antibiotic resistance. These data support further study and warrant reevaluation of current treatment practices.

Case-Control Studies↗
PubMed2000

TRAIL expression in vascular smooth muscle.

TRAIL is a cell-associated tumor necrosis factor-related apoptosis-inducing ligand originally identified in immune cells. The ligand has the capacity to induce apoptosis after binding to cell surface receptors. To examine TRAIL expression in murine vascular tissue, we employed in situ hybridization and immunohistochemistry. In these studies, we found that TRAIL mRNA and protein were specifically localized throughout the medial smooth muscle cell layer of the pulmonary artery. Notably, a similar pattern of expression was observed in the mouse aorta. Consistent with these findings, we found that cultures of primary human aorta and pulmonary artery smooth muscle cells express abundant TRAIL mRNA and protein. We also found that these cells and endothelial cells undergo cell lysis in response to exogenous addition of TRAIL. Last, we confirmed that TRAIL specifically activated a death program by confirming poly(ADP ribose) polymerase cleavage. Overall, we believe that these findings are relevant to understanding the factors that regulate cell turnover in the vessel wall.

Animals↗
PubMed2000

Apoptosis in lung pathophysiology.

As recently as 1993, fewer than 10 manuscripts had been published on the topic of apoptosis specifically in the lung. Although that number is increasing, far fewer papers appear each year on apoptosis in the lung than in the other major organs. Therefore, our knowledge of this important aspect of lung cell physiology is relatively rudimentary. Recent literature is beginning to define important roles for apoptosis in normal lung cell turnover, lung development, and the pathogenesis of diseases such as interstitial pulmonary fibrosis, acute respiratory distress syndrome, and chronic obstructive pulmonary disease. Although the involvement of lung cell apoptosis in each of these examples seems clear, the many factors comprising the normal and abnormal regulation of cell death remain to be elucidated and are likely to be different in each situation. The definition of those factors will be an exciting and challenging field of research for many years to come. In that context, the goal of this symposium was to discuss, from a physiological perspective, some of the most recent and exciting advances in the definition of signaling mechanisms involved in the regulation of apoptosis specifically in lung cell populations.

Animals↗
PubMed2000

Patients on chronic peritoneal dialysis for ten years or more in North America.

Thirty-six patients on peritoneal dialysis (PD) for more than ten years in six North American centers were analyzed retrospectively. In the six centers, the percentage of patients surviving for more than ten years varied between 0.8% and 7.3%. The study group included 27 females and 9 males aged 38.6 +/- 14.2 years [mean +/- standard deviation (SD)] at the start of treatment. Of the 36 patients, 28 were Caucasian. The most common cause of end-stage renal disease (ESRD), present in 12 patients, was chronic glomerulonephritis. Only 4 patients had diabetes. At the beginning of the study, 19 patients had hypertension (the most common comorbid condition); 11 had no comorbid conditions at the start. Creatinine clearance at the start was 4.12 +/- 3.5 mL per minute, and the mean duration to anuria was 51 +/- 25 months. Mean initial body weight was 55 +/- 9 kg, and mean body surface area was 1.5 +/- 0.2 m2. Serum albumin levels showed an increase from 33.8 +/- 3.6 g/L at the start of the study to 38.2 +/- 3.9 g/L at the end. Hospitalization rate was low at 0.5 +/- 0.3 admissions per patient-year, and duration of hospitalization was 4.8 +/- 3.7 days per patient-year. Peritonitis was the most common cause of hospitalization. The mean peritonitis rate was 1 episode every 52 +/- 48 patient-months. There were 36 catheter changes in 18 patients; 16 patients had a single PD catheter throughout the period of study. Autonomous hyperparathyroidism was the most common long-term complication. At the end of the study period, 11 patients were still on PD, 9 had died, 5 had been transferred to hemodialysis (HD), 1 was alive with a functioning allograft, and 1 was lost to follow-up. We conclude that patients who survive longer than ten years on PD are most likely to be young Caucasian females, small in body size, who are non diabetic, with few comorbid conditions. These long-term survivors have few hospitalizations, and their peritonitis rate is low. In this group of patients, severe autonomous hyperparathyroidism is the most common long-term complication.

Adolescent↗
PubMed2000

Health care systems: the emperor has no clothes.

Stand-alone hospitals are becoming something of a rarity on the American landscape. While hospital boards have repeatedly voted to form systems in the last 10 to 20 years, they have been just as likely to neglect to identify specific, measurable benefits that a merger would bring to their institution. An even if they did, they frequently discontinued evaluating whether system formation brought the hoped-for benefits, thereby justifying ongoing system participation. It is an incumbent fiduciary obligation to continually ask the question: Does continued participation make sense; that is, are we appropriately exercising stewardship over the hospitals' or system's assets by participating in this system? In a sense, boards are in danger of becoming like the emperor in the children's fairy tale, believing they have done the right thing without taking a hard look at today's reality.

Contract Services↗
PubMed1999

Characterization of a novel cis-element that regulates Fas ligand expression in corneal endothelial cells.

Constitutively expressed Fas ligand in the cornea, Sertoli cell of the testes, Paneth cell of the intestines, and Clara cell of the airway protect surrounding parenchymal tissue by inducing apoptosis of Fas(+) immune cells during inflammatory reactions. Indeed, the action of corneal Fas ligand has been suggested to facilitate successful allogeneic cornea transplantation. To study the transcriptional regulation of Fas ligand in the eye, we employed an immortalized mouse corneal endothelial cell line (C3H3) that constitutively expresses Fas ligand. By deletion analysis of the mouse Fas ligand promoter, gel mobility shift assays, and site-directed mutagenesis, we found that a TCCT motif located -299 base pairs upstream from the transcriptional start site served as a major positive regulatory cis-element in C3H3 cells. In contrast, this element was not required for Fas ligand transcriptional activity in Sertoli cells and airway epithelial cells. By UV cross-linking analysis, we found that an approximately 30-kDa corneal nuclear protein binds to the Fas ligand promoter TCCT box and, thus, likely plays an important role in Fas ligand expression in corneal endothelial cells.

Animals↗
PubMed1999

FasL promoter activation by IL-2 through SP1 and NFAT but not Egr-2 and Egr-3.

Recently activated peripheral T cells treated with IL-2 for 4 days expressed Fas ligand (FasL)-mediated cytotoxicity. These IL-2-treated T cells had high nuclear expression of SP1 and NFAT, but lacked the Egr-2 and Egr-3 that could be induced by anti-CD3 stimulation and had been implicated in FasL gene activation. A minimal promoter region that responded to IL-2 was identified by transient transfection assays using deletion mutants. The data suggests that the GGGCGGAAA site present in the 5' end of the minimal FasL promoter is critical to IL-2-induced FasL gene activation. The GGGCGGAAA sequence contains an overlapping site used by two transcription factor families, one (GGGCGG) for the SP1 family and the other (GGAAA) for the NFAT family. FasL promoter activity was partially but statistically significantly reduced with constructs mutated at either site. More activity was lost with a construct mutated at both sites. In contrast, mutation at the Egr site had no effect on IL-2-induced FasL promoter activity. Our study identified a new FasL promoter site responding to IL-2-induced SP1 and NFAT factors. Furthermore, the nuclei of IL-2-treated cells express SP1 and NFAT, but not Egr-2 and Egr-3, for FasL gene activation.

Animals↗
PubMed1999

Single synaptic events evoke NMDA receptor-mediated release of calcium from internal stores in hippocampal dendritic spines.

We have used confocal microscopy to monitor synaptically evoked Ca2+ transients in the dendritic spines of hippocampal pyramidal cells. Individual spines respond to single afferent stimuli (<0.1 Hz) with Ca2+ transients or failures, reflecting the probability of transmitter release at the activated synapse. Both AMPA and NMDA glutamate receptor antagonists block the synaptically evoked Ca2+ transients; the block by AMPA antagonists is relieved by low Mg2+. The Ca2+ transients are mainly due to the release of calcium from internal stores, since they are abolished by antagonists of calcium-induced calcium release (CICR); CICR antagonists, however, do not depress spine Ca2+ transients generated by backpropagating action potentials. These results have implications for synaptic plasticity, since they show that synaptic stimulation can activate NMDA receptors, evoking substantial Ca2+ release from the internal stores in spines without inducing long-term potentiation (LTP) or depression (LTD).

6-Cyano-7-nitroquinoxaline-2,3-dione↗