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Biomedical subjects

J E Fischer

Publications and source records attributed to J E Fischer.

At least 91 records · Page 5Linked to original sources
PubMed1998

Percutaneous central venous catheterization in premature infants: a method for facilitating insertion of silastic catheters via peripheral veins.

Peripheral venous cannulation is the preferred method of inserting central venous silastic catheters in premature infants. The standard techniques are placement of the catheter using a breakaway introducer needle or introduction of the catheter through a cannula. In extremely low birth weight infants (<1000 g) successful cannulation is impeded by the small size of the vessels. After repeated attempts, both procedures can be time-consuming and stressful to the infant. We present a modified insertion technique of the standard 2-French silastic catheter with an increased success rate, thus reducing insertion time, stress to the infant, and costs. The method uses the tip of a 20-gauge cannula as dilator/introducer for the 2-French catheter. This tip is inserted into the vessel with a standard 24-gauge cannula. After successful insertion of the dilator/introducer cannula, the standard 2-French catheter can then be advanced easily.

Catheterization, Central Venous↗
PubMed1998

The molecular regulation of protein breakdown following burn injury is different in fast- and slow-twitch skeletal muscle.

We compared the effect of burn injury on the energy-ubiquitin-dependent proteolytic pathway in the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus muscle in rats. Rats were subjected to a 30% total body surface area full-thickness burn or sham procedure. At various time points after injury, total and myofibrillar protein breakdown rates were determined in incubated EDL and soleus muscles. The energy-dependent component of protein break-down was determined by incubating muscles in energy-depleting medium. Messenger RNA levels for ubiquitin and RC3, a 20S proteasome subunit, were measured by Northern blot analysis. Burn injury resulted in an approximately 50% increase in total protein breakdown and a 3-4 fold increase in myofibrillar protein breakdown in EDL muscles, and this response reflected increased energy-dependent protein breakdown. In contrast, protein breakdown rates were not significantly influenced by the burn injury in soleus muscles. Ubiquitin mRNA levels were increased almost 10-fold in EDL and approximately 4.5-fold in soleus muscles following burn injury. Burn injury resulted in a 2-fold increase in RC3 mRNA in EDL with no significant changes noted in soleus muscles. The results suggest that the more pronounced effect of burn injury on protein breakdown in fast-twitch than in slow-twitch muscle may reflect different regulation of proteolysis at the molecular level.

Animals↗
PubMed1998

Proteasome blockers inhibit protein breakdown in skeletal muscle after burn injury in rats.

1. Burn injury stimulates ubiquitin-dependent protein breakdown in skeletal muscle. The 20S proteasome is the proteolytic core of the 26S proteasome that degrades ubiquitin conjugates. We examined the effects of the proteasome inhibitors N-acetyl-L-leucinyl-L-leucinal-L-norleucinal (LLnL), lactacystin and beta-lactone on protein breakdown in muscles from burned rats. 2. A full-thickness burn of 30% total body surface area was inflicted on the back of rats. Control rats underwent a sham procedure. After 24 h, extensor digitorum longus muscles were incubated in the absence or presence of 20S proteasome blocker and protein turnover rates and ubiquitin mRNA levels were determined. 3. LLnL resulted in a dose- and time-dependent inhibition of total protein breakdown in incubated muscles from burned rats. Lactacystin and beta-lactone blocked both total and myofibrillar muscle protein breakdown. In addition to inhibiting protein breakdown, LLnL increased ubiquitin mRNA levels, possibly reflecting inhibited proteasome-associated RNase activity. 4. Inhibited muscle protein breakdown caused by LLnL, lactacystin and beta-lactone supports the concept that the ubiquitin-proteasome pathway plays a central role in burn-induced muscle proteolysis. Because the proteasome has multiple important functions in the cell, in addition to regulating general protein breakdown, further studies are needed to test the role of proteasome blockers in the treatment or prevention of muscle catabolism.

Acetylcysteine↗
PubMed1997

Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle.

Previous studies provided evidence that sepsis-induced muscle proteolysis in experimental animals is caused by increased ubiquitin-proteasome-dependent protein breakdown. It is not known if a similar mechanism accounts for muscle proteolysis in patients with sepsis. We determined mRNA levels for ubiquitin and the 20 S proteasome subunit HC3 by Northern blot analysis in muscle tissue from septic (n = 7) and non-septic (n = 11) patients. Plasma and muscle amino acid concentrations and concentrations in urine of 3-methylhistidine (3-MH), creatinine, and cortisol were measured at the time of surgery to assess the catabolic state of the patients. A three- to fourfold increase in mRNA levels for ubiquitin and HC3 was noted in muscle tissue from the septic patients concomitant with increased muscle levels of phenylalanine and 3-MH and reduced levels of glutamine. Total plasma amino acids were decreased by approximately 30% in the septic patients. The 3-MH/creatinine ratio in urine was almost doubled in septic patients. The cortisol levels in urine were higher in septic than in control patients but this difference did not reach statistical significance. The results suggest that sepsis is associated with increased mRNAs of the ubiquitin-proteasome pathway in human skeletal muscle.

Aged↗
PubMed1997

Treatment of endotoxemic mice with anti-interleukin-6 antibody paradoxically increases interleukin-6 levels and stimulates mucosal protein synthesis.

OBJECTIVE: To test the role of interleukin-6 (IL-6) in the regulation of mucosal protein synthesis during endotoxemia. EXPERIMENTAL DESIGN: Three series of experiments were performed: (1) mice were injected with different doses of lipopolysaccharide (LPS) and protein synthesis was measured in jejunal mucosa at various time points up to 24 hours after injection of LPS; (2) mice were pretreated with anti-IL-6 antibody before injection of LPS; and (3) mice were injected with recombinant IL-6 and mucosal protein synthesis was measured 24 hours later. RESULTS: Treatment of mice with LPS resulted in a dose- and time-dependent increase in mucosal protein synthesis. Pretreatment of endotoxemic mice with anti-IL-6 antibody resulted in a paradoxical increase in plasma and tissue levels of IL-6 and a further increase in mucosal protein synthesis. Administration of IL-6 to normal mice resulted in increased mucosal protein synthesis. CONCLUSION: The increase in mucosal protein synthesis seen during endotoxemia may be regulated at least in part by IL-6.

Animals↗
PubMed1997

Complement C3 production in human intestinal epithelial cells is regulated by interleukin 1beta and tumor necrosis factor alpha.

BACKGROUND: Sepsis and endotoxemia are associated with increased mucosal production of complement component C3; the enterocyte may be a source of C3 in these conditions. OBJECTIVE: To test the hypothesis that interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) regulate the production of C3 in the enterocyte at the transcriptional level and that this regulation is potentiated by interferon gamma (IFN-gamma). METHODS: Cultured Caco-2 cells, a human intestinal epithelial cell line, were treated with various concentrations of human recombinant IL-1beta (0.005-1.25 ng/mL) or TNF-alpha (1-1000 U/mL) with or without the addition of IFN-gamma (250 U/mL). C3 levels in the culture medium were measured by enzyme-linked immunosorbent assay and cellular messenger RNA levels by Northern blot analysis. RESULTS: Treatment of the Caco-2 cells with IL-1beta or TNF-alpha resulted in a time- and dose-dependent increase in C3 production. The use of IFN-gamma alone did not affect C3 production but potentiated the effect of IL-1beta and TNF-alpha in a synergistic manner. C3 messenger RNA levels were increased following stimulation with either cytokine. CONCLUSIONS: C3 production in the enterocyte is regulated by IL-1beta and TNF-alpha at the transcriptional level, and this response is potentiated by IFN-gamma. The results suggest that C3 production in the intestinal mucosa may be regulated locally by cytokines in a paracrine or autocrine manner.

Caco-2 Cells↗
PubMed1997

mRNA differential display of colonic mucosa cells in ulcerative colitis.

Involvement of mucosal cells in inflammatory bowel disease (IBD) may be a sequenced process and the molecular difference between involved and uninvolved cells might implicate a possible mechanism in the disease process. The aim of this study was to compare gene expression between involved and uninvolved colonic mucosa cells in an individual with ulcerative colitis (UC) and to clone, sequence, and identify those differentially expressed genes, mRNA differential display was used to identify the gene expression in the mucosa of the UC patient. Anchored oligo(dT) primers and random 5' oligonucleotide 10-mer were used to carry out polymerase chain reaction on reverse-transcribed RNA (RT-PCR). The amplified cDNAs were displayed on a standard sequencing gel and comparisons were drawn between each two lanes representing either involved or uninvolved cells from a specific combination of two primers. Wherever differences were noted between lanes, the bands were reamplified using PCR, cloned into specialized vectors for positive selection, and then confirmed by dot blot. The cloned genes were then sequenced and compared with the GenBank database. About 1200 mRNA species were displayed in the sequencing gel. Among them, 106 fragments were differentially expressed between the two groups. Twenty-five of those differentially displayed gene fragments have been isolated, reamplified, and cloned for sequencing and dot blot analysis. Seventeen of the fragments were differentially expressed using the dot blot technique. Among those 25 gene fragments, 14 have homology to known genes and 11 have no match to any reported genes. Those matched known genes included genes for parathyroid tumor, T cell receptor-beta, alpha-nascent polypeptide-associated complex, ovarian cancer, and myeloblast. This is the first study using mRNA differential display to observe differential gene expression between involved and uninvolved mucosa cells in UC and it shows that differential display is a rapid method for characterizing gene changes in vivo in ulcerative colitis. The results from this study may provide useful information and facilitate further gene studies in this disease.

Autoradiography↗
PubMed1997

IL-6 production in human intestinal epithelial cells following stimulation with IL-1 beta is associated with activation of the transcription factor NF-kappa B.

Recent studies suggest that interleukin-1 beta (IL-1 beta) stimulates interleukin-6 (IL-6) production in human intestinal epithelial cells, but the intracellular mechanisms of this response are not known. In other reports, the nuclear factor-kappa B (NF-kappa B) regulated IL-6 production in certain cell types. We tested the hypothesis that IL-6 production in the enterocyte is associated with activation of NF-kappa B. Caco-2 cells, a human intestinal epithelial cell line, were grown in tissue culture whereafter they were treated with IL-1 beta (0.5 ng/ml). Cells were preincubated with pyrrolidine dithiocarbamate (PDTC; 10-500 microM), tosyl-lys-chloromethylketone (TLCK; 10-500 microM), or genistein (25-75 microM), all of which are known inhibitors of NF-kappa B. IL-6 levels in the culture media were measured after 24 hr by enzyme-linked immunosorbent assay (ELISA) and IL-6 messenger RNA (mRNA) levels were determined after 4 hr by competitive reverse-transcriptase polymerase chain reaction (RT-PCR). NF-kappa B activity was determined by electrophoretic gel mobility shift assay (EMSA). PDTC, TLCK, and genistein each inhibited IL-1 beta-induced IL-6 production by the Caco-2 cells in a dose-dependent fashion. These responses were also associated with a decrease in IL-6 mRNA levels. There was no NF-kappa B activity in untreated cells, but the addition of IL-1 beta resulted in the activation of NF-kappa B as determined by EMSA. The results suggest that IL-1 beta-induced IL-6 production in the enterocyte is associated with activation of NF-kappa B. The inhibition of IL-6 production by the NF-kappa B inhibitors indicates that the IL-6 production is regulated by NF-kappa B, although further experiments are needed to test that hypothesis.

Caco-2 Cells↗
PubMed1997

Increased glutamine consumption in small intestine epithelial cells during sepsis in rats.

BACKGROUND: Previous reports have emphasized increased intestinal glutamine consumption during sepsis. This may be of clinical significance as glutamine is a (and perhaps the) physiologic fuel for the intestine. A problem remains, however, as glutaminase, the major enzyme for the degradation of glutamine, is decreased rather than increased in sepsis. This implies an alteration in the metabolic fate of glutamine in sepsis, which may be of clinical significance. METHODS: We determined the effect of sepsis on glutamine metabolism in mucosa of small intestine. Sepsis was induced in rats by cecal ligation and puncture. Control rats were sham-operated. After 16 hours, glutamine consumption was measured in isolated enterocytes, and glutaminase, glutamine synthetase, and glutamine transaminase activities and DNA synthesis were determined in mucosa. RESULTS: Glutamine consumption was increased during sepsis in enterocytes from the tips of the villi and was unchanged in enterocytes from the midportions of the villi and the crypts. As previously shown, mucosal glutaminase activity was reduced. However, glutamine synthetase and glutamine transaminase activities were stimulated in septic rats, suggesting an increase in metabolism of glutamine via alternate pathways. DNA synthesis was increased during sepsis, especially in crypt cells. CONCLUSIONS: Increased or unchanged glutamine consumption in enterocytes from septic rats, despite reduced glutaminase activity, appears to reflect increased activity of other enzyme systems and/or increased utilization of the amino acid for DNA and protein synthesis. Since other aspects of glutamine metabolism may also be deranged in sepsis, a continual enteral supply of glutamine to the intestinal lumen during sepsis may be clinically useful.

Animals↗
PubMed1997

Implementation of a clinical pathway decreases length of stay and hospital charges for patients undergoing total colectomy and ileal pouch/anal anastomosis.

BACKGROUND: Clinical pathways are increasingly being used by hospitals to improve efficiency in the care of certain patient populations; however, little prospective data are available to support their use. This study examined whether using a clinical pathway for patients undergoing ileal pouch/anal anastomosis, a complex procedure in which we had extensive practical experience, affected hospital charges or length of stay (LOS). METHODS: A clinical pathway was developed to serve patients undergoing elective total colectomy and ileal pouch/anal anastomosis. All operations were performed by two attending physicians (J.E.F., M.S.N.). Before implementation, 10 pilot patients were prospectively monitored to ensure that hospital charges were accurately generated. In addition, charge audits were performed by an outside agency to verify the accuracy of the hospital bills. The pathway was then implemented, and 14 patients were prospectively analyzed. RESULTS: In all patients the principal diagnosis was ulcerative colitis, with the exception of three patients with familial polyposis. Mean external audit charges were within 2% of the hospital bills; therefore the hospital bills were used in all calculations. The mean LOS decreased from 10.3 days to 7.5 days (p = 0.046) for patients on the pathway versus pilot patients. Mean hospital charges also decreased significantly, from $21,650 to $17,958 per patient (p = 0.005). CONCLUSIONS: Implementation of a clinical pathway, even for an operation in which the surgeon has much experience, is an effective method for reducing LOS and charges for patients. This is likely the result of interdisciplinary cooperation, elimination of unnecessary interventions, and streamlined involvement of ancillary services. These results support the development of clinical pathways for procedures that involve routine preoperative and postoperative care. In addition, the benefits of clinical pathways should increase proportionally with increasing case volume for a particular procedure.

Adenomatous Polyposis Coli↗
PubMed1997

Sepsis and endotoxaemia in mice stimulate the expression of interleukin-I and interleukin-6 in the central nervous system.

1. In previous studies, experimental endotoxaemia was found to stimulate cytokine production in the central nervous system. The effect of sepsis on brain cytokines is not fully known. We compared the effect of endotoxaemia and sepsis on brain interleukin-1 and interleukin-6 expression. 2. Male A/J mice were injected subcutaneously with lipopolysaccharide (10 mg/kg) or an equal volume of saline as control. Sepsis was induced by caecal ligation and puncture (CLP); control mice underwent sham-operation. Brain tissue was assayed for interleukin-1 and interleukin-6 by ELISA. Northern blotting or the polymerase chain reaction was used to determine cytokine mRNA levels. 3. Administration of endotoxin induced a greater than fourfold increase in brain interleukin-1, a greater than threefold increase in interleukin-6 and an increase in mRNA for both cytokines. Caecal ligation and puncture resulted in increased brain interleukin-1 and interleukin-6 levels, but the changes were less pronounced and occurred later than after injection of endotoxin. There was no detectable difference in brain interleukin-1 mRNA between septic and sham-operated mice, whereas interleukin-6 mRNA was increased in brains of septic animals. 4. Sepsis and endotoxaemia resulted in similar, although not identical, changes in brain interleukin-1 and interleukin-6 concentrations and mRNA levels, suggesting that increased cytokine production in the central nervous system is part of the systemic response to sepsis and may be mediated by endotoxin.

Animals↗
PubMed1997

The ubiquitin-proteasome pathway: review of a novel intracellular mechanism of muscle protein breakdown during sepsis and other catabolic conditions.

SUMMARY BACKGROUND DATA: Patients with sepsis and other catabolic conditions, such as severe trauma, cancer, and fasting, suffer significant loss of body protein, the majority of which originates from skeletal muscle. Recent evidence suggests that muscle protein breakdown during sepsis is caused by upregulated activity in the ubiquitin-proteasome pathway and is associated with increased expression of the ubiquitin gene. PURPOSE: The purpose of the study was to review the role of the ubiquitin-proteasome pathway in the regulation of muscle proteolysis during sepsis and other catabolic conditions. REVIEW: Proteins that are degraded by the ubiquitin-proteasome mechanism are first conjugated to ubiquitin, a 76-amino-acid, highly conserved residue. Ubiquitinated proteins are recognized by the 26S proteasome, which is a large proteolytic complex consisting of the 19S cap complex and the 20S proteasome. The 20S proteasome is a cylindrical particle composed of four stacked rings, making it look like a barrel. The rings form a "tunnel" in which the target proteins are hydrolyzed, after which ubiquitin is released to be reused in the proteolytic pathway. A unique feature of the ubiquitin-proteasome proteolytic pathway is its energy dependency. CONCLUSIONS: An understanding of the molecular regulation of protein metabolism in patients with sepsis and other catabolic conditions is important because it may form the basis for improved treatment in the future.

Cysteine Endopeptidases↗
PubMed1997

Interleukin-1 beta and interferon-gamma regulate interleukin-6 production in cultured human intestinal epithelial cells.

Recent studies suggest that interleukin-6 (IL-6) is produced in the intestinal mucosa during sepsis and endotoxemia and that the enterocyte may be a source of IL-6 in these conditions. The regulation of IL-6 production in the enterocyte is not fully understood. We tested the hypothesis that IL-6 production in the enterocyte is regulated by proinflammatory cytokines. This was done by treating cultured Caco-2 cells, a transformed human intestinal epithelial cell line, with different concentrations of tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6 or interferon-gamma (IFN-gamma). IL-6 production by the Caco-2 cells was determined by ELISA. The expression of IL-6 mRNA was determined by reverse-transcriptase polymerase chain reaction. IL-6 was not produced in unstimulated Caco-2 cells. Treatment of the Caco-2 cells with IL-1 beta resulted in a dose- and time-dependent stimulation of IL-6 production with a maximal effect noted at an IL-1 beta concentration of .5 ng/mL at 24 h. IFN-gamma alone did not stimulate IL-6 production but potentiated the effect of IL-1 beta in a synergistic fashion. Treatment of the Caco-2 cells with IL-1 beta induced expression of IL-6 mRNA with a response noticed after 30 min. TNF-alpha and IL-6 did not influence the production of IL-6 in the Caco-2 cells. The results suggest that enterocyte IL-6 production is stimulated by IL-1 beta and that this effect is potentiated by IFN-gamma. The regulation of IL-6 production in the enterocyte may be specific for IL-1 beta, since neither TNF nor IL-6 stimulated IL-6 production.

Adjuvants, Immunologic↗
PubMed1997

Cytokines block the effects of insulin-like growth factor-I (IGF-I) on glucose uptake and lactate production in skeletal muscle but do not influence IGF-I-induced changes in protein turnover.

There is evidence that proinflammatory cytokines are involved in the regulation of muscle protein breakdown in various catabolic conditions but the mechanisms are not fully understood. Previous studies suggest that cytokines reduce circulating and tissue levels of insulin-like growth factor-I (IGF-I) and may block the anabolic effects of the hormone in certain cell types and tissues. We tested the hypothesis that a mixture of tumor necrosis factor alpha, interleukin-1 alpha, and interferon-gamma block the anabolic effects of IGF-I in skeletal muscle. Muscles from burned or unburned rats were incubated in the absence or presence of 1 microgram/mL of IGF-I with or without the addition of the cytokines. As expected, IGF-I stimulated protein synthesis and inhibited protein breakdown in incubated muscles. The cytokines did not influence protein turnover rates in muscles incubated with or without IGF-I. In additional experiments, the effects of IGF-I on glucose uptake and lactate production were tested. IGF-I increased glucose uptake approximately 2.5-fold and stimulated lactate production approximately 5-fold. These effects of the hormone were significantly inhibited by the cytokine mixture. The results suggest that cytokines do not induce protein catabolism by directly inhibiting the anabolic effects of IGF-I in muscle tissue. The inhibitory effects of the cytokines on IGF-I-stimulated glucose transport and lactate production suggest that the lack of effect of cytokines on protein metabolism was not due to a metabolic unresponsiveness of the incubated muscles to the cytokines.

Animals↗
PubMed1997

Neuropeptide Y treatment and food deprivation increase cyclic AMP response element-binding in rat hypothalamus.

Intrahypothalamic (IHT) administration of neuropeptide Y (NPY) induces a robust feeding response in rats. We have shown previously that NPY-induced feeding is mediated by a pertussis-toxin-sensitive G protein in rats. NPY receptors are coupled to cAMP and Ca2+. Because these second messengers are known to activate cAMP response element binding proteins, (CREB), cAMP response element modulators, or activating transcription factor 1, we investigated the involvement of these transcription factors in NPY-induced feeding in rats. Compared with control injections of cerebrospinal fluid (1 microl), IHT administration of NPY increased cAMP response element (CRE) binding to rat hypothalamic nuclear extracts in a time-dependent manner, as detected by an electrophoretic mobility shift assay. In contrast, IHT administration of the anorectic neuropeptide, pituitary adenylate cyclase activating polypeptide, strongly inhibited the CRE binding. Food deprivation for 48 hr also increased CRE binding, whereas 8 hr of refeeding normalized CRE activity. Preincubation of the hypothalamic nuclear extracts of NPY-treated and unfed rats with antibody specific to CREB blocked CRE binding, whereas preincubation with phosphoCREB antibody retarded the migration of CRE-protein complex, indicating that phosphoCREB is involved in this process. Consistently, immunohistochemical studies with food-deprived rats showed an intense phosphoCREB signal in the paraventricular nuclei and ventromedial hypothalamus in comparison to rats fed ad libitum. Hypothalamic calcium/calmodulin-dependent protein kinase II activity was also increased by IHT-NPY. These results suggest that calcium/calmodulin-dependent protein kinase II induced phosphorylation of CREB may be involved in regulating feeding behavior induced by NPY.

Animals↗
PubMed1997

Overexpression of interleukin-4 delays virus clearance in mice infected with respiratory syncytial virus.

Although interleukin-4 (IL-4) expression has been implicated in vaccine-enhanced respiratory syncytial virus (RSV) disease, its role in mediating the immune response to primary RSV infection remains unclear. To assess the effect of IL-4 production on typical RSV infection, transgenic mice which either overexpress or fail to express IL-4 were challenged intranasally with RSV and their responses were compared to those of the parent strains. IL-4-deficient mice eliminated virus from the lung as quickly as did C57BL/6 controls. In contrast, mice which constitutively overexpress IL-4 showed delayed virus clearance compared with mice of the FVB/N control strain, although peak viral titers did not differ. IL-4 overexpression increased the magnitude of the subsequent antibody response. Lung lymphocytes harvested from IL-4-overexpressing mice post-RSV challenge showed diminished RSV-specific cytolytic activity compared with controls. Both IL-4-deficient and IL-4-overexpressing strains resisted rechallenge. These data imply that constitutive IL-4 expression delays or suppresses the development of a virus-specific cytotoxic lymphocyte population important in clearing primary RSV infection.

Animals↗
PubMed1997

Intracellular regulation of protein degradation during sepsis is different in fast- and slow-twitch muscle.

We tested the hypothesis that the difference in the response to sepsis of protein breakdown between fast- and slow-twitch skeletal muscle reflects differential activation of the energy-ubiquitin-dependent proteolytic pathway. In addition, we defined the time course and the tissue specificity of sepsis-induced changes in the expression of the ubiquitin pathway. Sepsis was induced in rats by cecal ligation and puncture; control rats were sham operated. Energy-dependent protein breakdown was measured in incubated extensor digitorum longus (EDL) and soleus muscles. Ubiquitin mRNA levels were determined by Northern blot analysis. Sepsis resulted in increased energy-dependent protein breakdown and upregulated expression of ubiquitin mRNA in the fast-twitch EDL but not in the slow-twitch soleus muscle. The sepsis-induced increase in ubiquitin mRNA levels in the EDL muscle was noticeable before the increase in energy-dependent protein breakdown. Sepsis increased ubiquitin mRNA levels in the diaphragm (a mixed fiber-type muscle) but not in heart, liver, kidney, or intestine, consistent with a tissue-specific regulation of the ubiquitin system during sepsis. The results suggest that the difference in protein breakdown during sepsis between fast- and slow-twitch muscles reflects differential activation of the energy-ubiquitin-dependent proteolytic pathway. The data also suggest that the expression of the ubiquitin pathway is upregulated in a time-dependent fashion during sepsis and that this response is not a generalized phenomenon but is tissue specific.

Animals↗