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Biomedical subjects

A Fine

Publications and source records attributed to A Fine.

At least 109 records · Page 6Linked to original sources
PubMed1996

Regulation of type I collagen production by insulin and transforming growth factor-beta in human lung fibroblasts.

The effects and interaction of transforming growth factor-beta (TGF-beta) and insulin on collagen production in human fetal lung fibroblasts was examined. Fibroblasts were labeled with [3H]proline and collagen production was analyzed by polyacrylamide gel electrophoresis. The addition of insulin (2 micrograms/ml) increased collagen production 5 fold and TGF-beta (5 ng/ml) increased collagen production 6-fold. The combination of TGF-beta and insulin further increased type I collagen production (12 fold). We found that TGF-beta increased pro-alpha 1 (I) collagen mRNA levels 2-3 fold, insulin increased mRNA levels by less than 2 fold, and the combination stimulated a 3-4 fold increase. In a nuclear run-on assay, we found a 1.7 fold increase in the rate of transcription for the pro-alpha 1 (I) collagen gene in insulin-treated cultures and a 2-fold increase in TGF-treated cultures. In fibroblasts transfected with a plasmid containing 2.4 kb of the 5' flanking sequences of the human pro-alpha 1 (I) collagen gene, TGF-beta stimulated a 2.8 fold increase in promoter activity. In contrast, the addition of insulin stimulated a small increase (less than 2 fold) in the pro-alpha 1 (I) collagen promoter activity when administered alone or in combination with TGF-beta. Insulin prolonged the half-life of pro-alpha 1 (I) collagen mRNA from 9.1 h to 14.3 h as assessed by treatment with actinomycin D. The insulin-induced increase in pro-alpha 1 (I) collagen mRNA was blocked by the presence of cycloheximide indicating a requirement for new protein synthesis. These results show that the combination of TGF-beta and insulin stimulate large increases in type I collagen formation by acting at different sites in the collagen biosynthetic pathway.

Collagen↗
PubMed1996

L-DOPA/carbidopa for nocturnal movement disorders in uremia.

Restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) are sleep disorders that are common and distressing to uremic patients. There are few data regarding effective treatment in this population. Five chronic hemodialysis patients completed a double-blind, placebo-controlled, crossover study using a single bedtime dose of controlled release L-DOPA/carbidopa (100/25 mg) for treatment of RLS and sleep disruption. Leg movements per hour of sleep and percentage of sleep time accompanied by leg movements were decreased with treatment (101.0 +/- 29.1 events/hour on placebo vs. 61.0 +/- 28.3 events per hour on drug, p = 0.006; and 15.1 +/- 4.9% of sleep time with leg movements on placebo vs. 8.6 +/- 4.0% on drug, p = 0.014). In addition, arousals associated with leg movements (mean 209 +/- 49 events on placebo, mean 108 +/- 46 events on drug) and the leg movement arousal index (mean 59 +/- 23 events/hour on placebo, mean 23 +/- 9 events/hour on drug) were decreased by active medication (p = 0.03 and 0.04, respectively). Patients, however, continued to have very disrupted sleep and we could not document consistent subjective or objective improvement in overall sleep except for an increase in slow-wave sleep (SWS) from 9.0% to 22.8% (p = 0.01). The patterns of movements during sleep were not uniform in different patients, and the movements, although often periodic, were much longer than defined for PLMS. Because of this, finding suitable objective parameters to analyze was problematic. Measuring the percentage of sleep time during which there were leg movements was probably the most efficient and reproducible means of quantitating this disorder. Thus, although controlled-release L-DOPA/carbidopa at a dose of 100/25 mg given once nightly reduced leg movements and increased SWS, sleep continued to be disrupted. Whether higher doses or more frequent dosing is effective requires further investigation.

Aged↗
PubMed1995

Discordant regulation of transforming growth factor-beta receptors by prostaglandin E2.

The effect of PGE2 on TGF-beta receptor binding was assessed for both signaling (type I and type II) and non-signaling (type III) TGF-beta receptors. We found in cross-linking studies that PGE2 treatment (24 h) decreased binding of TGF-beta to the type I and type II receptors by approx. 50% and markedly increased binding of TGF-beta to type III receptors nearly 10-fold. Northern analyses indicated that PGE2 decreased type I receptor mRNA levels by approximately 30-50%, decreased type II receptor mRNA levels by approximately 60%, and markedly increased type III receptor mRNA levels. Coincubation with cycloheximide partially blocked the PGE2-induced inhibition of type II receptor mRNA. In contrast, cycloheximide minimally affected PGE2-induced type III receptor mRNA levels. Activation of protein kinase C by phorbol esters had no apparent effect on TGF-beta receptor mRNA levels. Our data suggest that alterations in TGF-beta receptor expression could modify the response of tissues to TGF-beta during injury.

Animals↗
PubMed1995

Calciphylaxis presenting with calf pain and plaques in four continuous ambulatory peritoneal dialysis patients and in one predialysis patient.

Calciphylaxis is a rare disease associated with hemodialysis or transplantation, high parathyroid hormone values, and increased serum calcium x phosphate (Ca x P) product. Only four patients on continuous ambulatory peritoneal dialysis have been reported with this condition. We report five cases presenting within a 2-year period with severe calf pain and tenderness with extensive nonulcerating large, hard, and tender subcutaneous plaques in the calves. Calcium deposition was confirmed radiologically and by bone scanning. Four patients were on continuous ambulatory peritoneal dialysis, and the other was not yet on dialysis. High serum Ca x P product was found in three of these patients at onset of the condition. Two patients had normal parathyroid hormone levels at onset. Calcium salts and/or calcitriol had been taken prior to onset in three patients. When presenting in this fashion, the diagnosis can be easily made by the uniqueness of the physical findings in the legs. Our observation suggests that the condition should no longer be considered rare and is not confined to hemodialysis patients. Furthermore, it can occur in predialysis patients.

Aged↗
PubMed1995

Sleep complaints are common in a dialysis unit.

Sleep disturbance among uremic patients is reported to be high, but data on the actual prevalence, clinical significance, and causative factors is limited. A sleep questionnaire was distributed to an entire hemodialysis unit of 64 patients. Of the 54 patients who completed the survey, 83.3% had sleep-wake complaints. Disturbed sleep was reported by 28 patients (51.8%), and causes were secondary to delayed sleep onset in 25 patients (46.3%), frequent awakening in 19 patients (35.2%), restless legs syndrome (RLS) in 18 patients (33.3%), and generalized restlessness in six patients (11.1%). Daytime sleepiness was the most frequent complaint, reported by 36 patients (66.7%), and RLS was the second most frequent specific complaint, reported by 31 patients (57.4%). Symptoms of sleep apnea were described by seven patients (13.0%). Male gender, age more than 60 years, RLS, and caffeine intake were associated with more sleep-wake complaints (P = 0.009, P = 0.002, P = 0.028, and P = 0.008, respectively). Urea and creatinine levels were higher in patients with RLS (P = 0.04 and P = 0.08, respectively); otherwise, no other metabolic or demographic variable was associated with specific sleep disorders or disturbance. Sleep problems are very common in dialysis patients and likely contribute to the impaired quality of life experienced by many of these patients.

Adult↗
PubMed1995

Potential therapeutic initiatives for fibrogenic lung diseases.

Fibrotic process affecting the lung and other tissues is characterized by stimulation of fibroblast proliferation and connective tissue deposition. Conventional therapy consisting of glucocorticoids or cytotoxic agents is usually ineffective in blocking progression of disease. Potential new therapies have emerged from the use of animal models of pulmonary fibrosis and recent advances in the cellular and molecular biology of inflammatory reactions. Such therapies involve the use of substances directed against the action of certain growth factors, cytokines, or oxidants that are elaborated during the fibrotic reaction. In this article, we review possible therapeutic applications of these advances.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: evidence for changes in length and orientation associated with chemically induced LTP.

Using confocal microscopy in conjunction with microdrop application of Dil, we have imaged and measured individual dendritic spines of living hippocampal CA1 pyramidal neurons in acute brain slices, before and approximately 3 hr after induction of long-term potentiation by chemical means. Statistical analysis of changes in the length of individual spines, and comparison with results of Monte Carlo simulations, suggests that two forms of structural change occur in chemically induced long-term potentiation: growth of a subpopulation of small spines, and angular displacement of spines. These changes could provide a structural basis for the expression of long-term potentiation.

Algorithms↗
PubMed1994

Quantitative three-dimensional confocal microscopy of synaptic structures in living brain tissue.

In order to study changes in synaptic structure that accompany learning and memory, we have developed optical methods to visualize dendritic spines and presynaptic terminals in living, electrically monitored brain slices maintained in vitro. Focal microapplication of the fluorescent lipophilic dye DiI provides Golgi-like staining of small numbers of cells and processes that can be resolved clearly using confocal microscopy; viability of stained cells is established by exclusion of the fluorescent DNA-binding dye ethidium bromide. Serial optical sections are enhanced by deconvolution and other image processing methods. The resulting high-resolution images are combined in an automated procedure to generate three-dimensional reconstructions, in which submicron synaptic structures can be viewed and measured. These unbiased methods allow volume changes in individual, living synaptic structures to be assessed quantitatively over periods of hours or days in development or in response to stimulation, drug application, or other perturbations.

Animals↗
PubMed1994

Retinoic acid-induced inhibition of type I collagen gene expression by human lung fibroblasts.

We examined alpha 1(I) collagen gene expression in all-trans retinoic acid (RA)-treated human lung fibroblast cultures. RA (10(-5)M) decreased steady-state levels for alpha 1(I) collagen mRNA by at least 75% after 24 h. The inhibition was evident within 8 h after addition of RA, was dose dependent and reversible. Treatment with 9-cis-retinoic acid did not affect alpha 1(I) collagen mRNA levels. RA also inhibited the increases in alpha 1(I) mRNA stimulated by transforming growth factor-beta (TGF-beta). The RA-mediated decrease in alpha 1(I) collagen mRNA was blocked by cycloheximide treatment, suggesting that synthesis of a protein intermediate is required for the inhibition. The RA-induced decrease in alpha 1(I) collagen mRNA levels was not mediated by increases in prostaglandin E2 production. RA decreased alpha 1(I) gene transcription as determined by nuclear run-off assays but did not significantly alter the rate of degradation of the alpha 1(I) transcript as determined by actinomycin D treatment. Studies employing cells stably transfected with constructs containing portions of the alpha 1(I) collagen promoter indicate that the DNA sequences which mediate the inhibitory effect are located within 900 bases from the transcription start site.

Ascorbic Acid↗
PubMed1994

Structure and expression of the promoter for the human type II transforming growth factor-beta receptor.

The type II TGF-beta receptor is a serine/threonine kinase whose expression is essential for the action of TGF-beta. In this paper, we describe the cloning and expression of the human type II TGF-beta promoter. DNA sequence analysis indicates that the region near the transcription initiation site lacks a TATA and CAAT box but contains Sp1 binding sites. A similar promoter type has been identified in the 5' flanking regions of genes that code for certain other growth factor receptors. Transfection of the promoter (888 bp fragment) mediated transcriptional activity in bovine vascular smooth muscle cells and human lung fibroblasts.

Animals↗
PubMed1994

Genetic linkage of autosomal dominant juvenile glaucoma to 1q21-q31 in three affected pedigrees.

Glaucoma is a common disorder that results in irreversible damage to the optic nerve, causing absolute blindness. In most cases, the optic nerve is damaged by an elevation of the intraocular pressure that is the result of an abnormality in the normal drainage function of the trabecular meshwork. A family history of glaucoma is an important risk factor for the disease, suggesting that genetic defects predisposing to this condition are likely. Three pedigrees segregating an autosomal dominant juvenile glaucoma demonstrated significant linkage to a group of closely spaced markers on chromosome 1. These results confirm the initial mapping of this disease and suggest that this region on chromosome 1 contains an important locus for juvenile glaucoma. We describe recombination events that improve the localization of the responsible gene, reducing the size of the candidate region from 30 to 12 cM.

Adult↗
PubMed1994

Type I collagen formation in rat type II alveolar cells immortalised by viral gene products.

BACKGROUND: Alveolar type II (T2) cells synthesise matrix proteins such as type IV collagen and fibronectin. In contrast, a fetal rat T2 cell line has been shown to synthesise type I and III collagen as well as type IV collagen. To study regulation of collagen production in T2 cells, neonatal T2 cells immortalised by adenoviral 12SE1A gene transfer were used. It was previously reported that this immortalised cell line (E1A-T2) retains epithelial features such as tight junctions and cytokeratins but also expresses mesenchymal features such as vimentin. METHODS: Collagen production was examined in E1A-T2 and primary neonatal T2 cells using polyacrylamide gel electrophoresis. Electron microscopy was used to examine collagen deposition in E1A-T2 cell culture. To define the mechanism by which alpha 1(I) type I collagen gene expression was activated in E1A-T2 cells, a deletional analysis of alpha 1(I) promoter constructs linked to the bacterial chloramphenicol acetyltransferase gene was performed. RESULTS: E1A-T2 cells produced large amounts of type I collagen with a predominance of alpha 1(I) homotrimers; alpha 2(I) peptides were detected only in the cell layer. In contrast, primary neonatal rat T2 cell cultures produced a trace amount of type I collagen. Production of alpha 1(I) peptide chains (per microgram DNA) in E1A-T2 cell cultures was 30 times higher than that observed in primary neonatal T2 cell cultures. Electron microscopy showed deposition of type I collagen fibrils in the extracellular matrix of E1A-T2 cell cultures. Transfection studies suggested at least two cis-acting elements which mediate increased alpha 1(I) gene expression in E1A-T2 cells. CONCLUSIONS: These studies indicate that the E1A-T2 cell line may be useful for studying type I collagen gene regulation in alveolar T2 cells. These findings also raise the possibility that viral activation of type I collagen genes in alveolar epithelium may be involved in certain forms of pulmonary fibrosis.

Animals↗
PubMed1994

[The nursing infant at the intersection of different bodies of knowledge].

The effects of baby children's feeding on their mortality is known. It is thus interesting to know the cultural context in which bottle-feeding was adopted. In the 1930s, many women in the Eastern Pyrenees abandoned breast-feeding on the advice of their doctor because, they said, they had bad milk that "poisoned" their baby. This idea, widely spread in France at the time, took place within a set of traditional images of maternal milk and its spoiling which referred to ancient and complex beliefs concerning feminine physiology and blood disorders. These ideas were shared by women as well as by doctors until a relatively recent date.

Bottle Feeding↗
PubMed1994

Higher incidence of peritonitis in native Canadians on continuous ambulatory peritoneal dialysis.

OBJECTIVE: To determine if the rate of peritoneal dialysis (PD)-related infections in our large Native population was higher than in non-Natives. DESIGN: Prospective study of PD-related infections, 1987 to 1993. PATIENTS: Forty-eight Natives and 136 non-Natives were studied. Comparisons of infection rates were made as well as determinations of the effect of diabetes and of dialysis techniques on infection rate. RESULTS: The chance of remaining free of peritonitis was far lower at 6 and 12 months in Natives versus non-Natives, 40% versus 76% at 6 months, and 24% versus 54% at 12 months (p < 0.01). Having diabetes or adding intraperitoneal insulin did not confer additional risk of peritonitis. The Y-line reduced the risk of peritonitis in non-Natives only. Exit-site infection (ESI) was significantly higher in Natives versus non-Natives, 0.42 versus 0.19 episodes per patient year (p < 0.01) mainly due to Staph. aureus. However, less than 30% of episodes of peritonitis were due to that organism. Staph. epidermidis peritonitis episodes were not more common in Native patients, whereas infections due to most other organisms were. CONCLUSION: The susceptibility to both peritonitis and exit-site infection is increased in Native Canadians compared to non-Natives. The nonprotective effect of the Y-line combined with increased peritonitis due to most organisms except Staph. epidermidis in Natives suggests that host factors could be important in these patients.

Adult↗