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Biomedical subjects

R Kreisberg

Publications and source records attributed to R Kreisberg.

At least 19 recordsLinked to original sources
PubMed1998

Soluble ICAM-1 (sICAM-1) in biliary atresia and its relationship to disease activity.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is strongly expressed on the bile ducts and hepatic parenchyma of livers with biliary atresia. A soluble, circulating form of this membrane protein has been found to be elevated in a number of inflammatory hepatic disorders. However, its expression in biliary atresia is unknown. The purpose of this study was to assess the presence of soluble ICAM-1 in infants with biliary atresia in relation to disease activity, degree of cholestasis, and standard liver function tests. MATERIALS AND METHODS: A total of nine patients (n = 9) with biliary atresia (seven) and neonatal hyperbilirubinemia (two) were studied (age range 6 weeks-9 years). Control samples were obtained from three healthy infants (2-10 months). Serum was collected from each patient and stored at -80 degrees C until assayed. Levels of sICAM-1 were measured in duplicate utilizing an ELISA method (Bioscource International). Standard liver function tests (conjugated bilirubin, gamma-glutamyl transpeptidase, alkaline phosphatase, alanine aminotransferase) were determined at the same time. Results are expressed as the means +/- SEM with statistical analysis by Mann-Whitney test. RESULTS: sICAM-1 levels were significantly elevated in all patients with biliary atresia (997 +/- 56 ng/ml) when compared to controls (P < 0.001). No correlation was found between sICAM-1 levels and conjugated bilirubin, gamma-glutamyl transpeptidase, alkaline phosphatase, and alanine aminotransferase levels or with clinical assessment of disease severity. CONCLUSIONS: sICAM-1 is markedly elevated in biliary atresia reflecting the immunopathology of the disease process but does not appear to correlate with markers of liver function. sICAM-1 may be useful in assessing the effects of immunomodulatory therapy.

Biliary Atresia↗
PubMed1998

Regulation of proximal tubular osteopontin in experimental hydronephrosis in the rat.

BACKGROUND: Osteopontin is a tubular-derived glycoprotein with macrophage chemoattractant properties. Our previous observations demonstrate that osteopontin is involved in the accumulation of macrophages within the renal cortex of rats following unilateral ureteral obstruction (UUO). METHODS: The present study performed Northern and Western blot analyses of isolated proximal tubular cells exposed to exogenous angiotensin II, and cultured rat proximal tubular cells subjected to one hour of cyclic mechanical stretch, which provided insight into mechanisms involving the proximal tubular renin-angiotensin system in the increased expression of cortical osteopontin following hydronephrosis. RESULTS: In situ hybridization, using a 35S-labeled antisense riboprobe, showed osteopontin mRNA transcription localized to the cortical tubules of the obstructed kidney. Freshly isolated proximal tubules incubated with angiotensin II (10-5 M) for one hour had increased osteopontin mRNA and protein expression by Northern and Western blot analyses, respectively. Pre-treatment of proximal tubules with losartan (10-5 M) for one hour prior to the addition of exogenous angiotensin II (10-5 M) decreased osteopontin mRNA and protein expression. Rat proximal tubule cells subjected to cyclic mechanical stretch for one hour exhibited a 2.1-fold increment in osteopontin mRNA levels, which was normalized following pre-treatment with losartan. CONCLUSIONS: This study provides evidence that angiotensin II, produced by the proximal tubule in the obstructed kidney as a result of mechanical injury, possibly mechanical stretch, may stimulate angiotensin II type I receptor activation, leading to up-regulated osteopontin expression and secretion by the proximal tubule, thereby facilitating macrophage recruitment into the renal interstitium.

Animals↗
PubMed1997

Increased expression of decorin in experimental hydronephrosis.

Transforming growth factor (TGF)-beta1 is a potential mediator of tubulointerstitial (TI) fibrosis in the rat unilateral ureteral obstruction (UUO) model. Decorin is a protein composed of a core protein and a chondroitin sulfate side chain and is capable of inactivating TGF-beta. Since TGF-beta strongly induces the synthesis of decorin in experimental glomerulonephritis, it was our intent to investigate whether altered decorin expression is operant in the rat UUO model. Renal cortical decorin mRNA levels initially became elevated (2.5-fold) in obstructed kidney (OBK) versus contralateral unobstructed kidney (CUK) 24 hours post-UUO and remained greater in the OBK specimens at 48 (2.3-fold), 96 (2.2-fold), and 168 (1.9-fold) hours post-ureteral ligation. Whole-body X-irradiation 11 days prior to UUO significantly reduced decorin mRNA at 24 and 96 hours post-UUO. On immunolabeling, decorin was only evident in the adventitia of blood vessels in CUK specimens at any time point after UUO. In contrast, OBK specimens initially demonstrated periglomerular and peritubular interstitial localization of decorin at 96 hours post-ureteral ligation, which became even more intense and diffuse in the tubulointerstitium at 168 hours post-UUO. On Western analysis, there were highly significant increases in decorin protein expression in the OBK versus the CUK specimens at 96 and 168 hours post-UUO. Levels of active TGF-beta1 in the renal cortex of OBK were 1.9- and 3.6-fold higher than CUK at 48 and 96 hours post-UUO. In summary, we demonstrated that post-UUO, decorin mRNA and protein expression is up-regulated in the renal cortex of OBK, but not CUK, specimens in a temporal parallel with active TGF-beta1 levels and macrophage infiltration. We postulate that the development of TI fibrosis in this model may be related to only a physiologic induction of decorin by TGF-beta, and that pharmacologic levels may be required to retard or prevent scarring via TGF-beta inhibition.

Animals↗
PubMed1995

Paired natural cysteine mutation mapping: aid to constraining models of protein tertiary structure.

This paper discusses the benefit of mapping paired cysteine mutation patterns as a guide to identifying the positions of protein disulfide bonds. This information can facilitate the computer modeling of protein tertiary structure. First, a simple, paired natural-cysteine-mutation map is presented that identifies the positions of putative disulfide bonds in protein families. The method is based on the observation that if, during the process of evolution, a disulfide-bonded cysteine residue is not conserved, then it is likely that its counterpart will also be mutated. For each target protein, protein databases were searched for the primary amino acid sequences of all known members of distinct protein families. Primary sequence alignment was carried out using PileUp algorithms in the GCG package. To search for correlated mutations, we listed only the positions where cysteine residues were highly conserved and emphasized the mutated residues. In proteins of known three-dimensional structure, a striking pattern of paired cysteine mutations correlated with the positions of known disulfide bridges. For proteins of unknown architecture, the mutation maps showed several positions where disulfide bridging might occur.

Algorithms↗
PubMed1994

Ferritin stimulation of a monokine inhibitor of lipopolysaccharide-augmented myelopoiesis is ferroxidase dependent.

Ferritin inhibition of myelopoiesis has been associated with intrinsic ferroxidase activity of heavy-chain ferritin and with production of a monokine inhibitor of lipopolysaccharide (LPS)-augmented monocytopoiesis. We report here that intrinsic ferroxidase activity of heavy-chain ferritin is required for stimulated production of the monokine inhibitor of LPS-augmented monocytopoiesis.

Amino Acid Sequence↗
PubMed1993

Cytokine mediation of the suppressive effect of ferritin on colony-stimulating factor-1-dependent monocytopoiesis.

Peptide-specific IgG from a rabbit immunized with an alanine-lysine-proline-arginine ((ALA1)-tuftsin) containing 14-mer "ferritin" peptide neutralized rat liver ferritin inhibition of in vitro CSF-1-dependent monocytopoiesis. Antiferritin IgG similarly neutralized the inhibitory effect of ferritin but did not neutralize peptide inhibition of the in vitro myelopoietic response. No cross-reactivity between the respective antibodies and Ag was detected either by Western immunoblot or by competitive ELISA. Depletion of adherent cells before marrow cell culture significantly reduced the inhibitory effect of ferritin but did not influence peptide inhibition of CSF-1-stimulated colony formation. Adherent marrow cells and P388D1 cells treated with both CSF-1 and ferritin, but not either alone, produced inhibitory supernatant culture media that were neutralized by antipeptide but not antiferritin IgG. High resolution molecular sieve chromatography of the inhibitory adherent marrow cell and P388D1 supernatants resolved two peaks of 50 to 60 kDa and approximately 30 kDa in each. The inhibitory activity in all four peaks was neutralized by antipeptide but not antiferritin IgG. The ferritin/CSF inhibitors were not further characterized although identity with IL-6, IL-8, TNF-alpha, transforming growth factor-beta, and IFN-alpha/beta could be eliminated. The results indicate that ferritin inhibition of CSF-1-dependent monocytopoiesis is mediated by an endogenously produced inhibitor, or inhibitors, that shares antigenic similarity with the (ALA1)-tuftsin-containing 14-mer peptide and that adherent marrow cells, most likely monocytes or macrophages, produce the endogenous inhibitors in response to both CSF-1 and ferritin.

Amino Acid Sequence↗
PubMed1993

Opposing effects of tumor necrosis factor alpha and leukemia inhibitory factor in lipopolysaccharide-stimulated myelopoiesis.

Three myelopoietically active, lipopolysaccharide (LPS)-stimulated monokines, interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), and leukemia inhibitory factor (LIF), were tested for effect in an in vitro model for LPS-induced inflammatory murine monocytopoiesis. Neither cytokine stimulated clonal proliferation of marrow-derived progenitors; however, both IL-1 alpha and TNF-alpha enhanced macrophage colony-stimulating factor (M-CSF)-dependent colony formation. The additional progenitors stimulated by IL-1 alpha and TNF-alpha to form colonies in response to M-CSF were equivalent to the precommitment, transitional progenitors stimulated by M-CSF and bacterial LPS. In addition, the additional colonies elicited by IL-1 alpha and TNF-alpha were not additive in cultures containing both M-CSF and LPS, indicating these colonies arose from the same LPS-responsive, two-signal-dependent transitional progenitors. Leukemia inhibitory factor did not influence M-CSF-stimulated colony formation; however, LIF effected a dose-dependent inhibition of colony formation by transitional progenitors responding to combinations of M-CSF and LPS, IL-1 alpha, TNF-alpha, or an additional transitional cell costimulant, substance P. Neutralizing anti-murine TNF-alpha antibodies abrogated transitional cell colony formation stimulated by combinations of M-CSF and TNF-alpha, IL-1 alpha, LPS, or substance P but had no effect on colony formation stimulated solely by M-CSF. The results indicate that TNF-alpha may be an important positive stimulus for commitment of progenitors to the mononuclear phagocyte lineage and that TNF-alpha may be the endogenous regulator of the costimulatory effects of LPS, IL-1, and substance P. In addition, the results indicate that LIF may play an opposing negative regulatory role acting to inhibit LPS and TNF-alpha stimulation of the transitional progenitors.

Animals↗
PubMed1992

Nanomolar cyclic adenosine and guanosine monophosphates stimulate macrophage colony-stimulating factor responsiveness by murine transitional progenitors.

Both 3':5' cyclic adenosine monophosphate (cAMP) and 3':5' cyclic guanosine monophosphate (cGMP) stimulated colony-stimulating factor 1 (CSF-1)-dependent colony formation by murine two-signal-dependent progenitors without influencing colony formation by committed CSF-1-responsive progenitors. The stimulatory effect was optimal at 10(-9) M and did not diminish with increasing concentrations of the cyclic nucleotides. The membrane-permeating analogs dibutyryl cAMP and 8-Br-cGMP similarly augmented colony formation by the transitional progenitors at 10(-9) M; however, with increasing concentration, enhancement diminished with eventual inhibition of total colony formation at micromolar concentrations. Stimulation by the two cyclic nucleotides was mutually incompatible. The results indicate that physiological levels of extracellular cyclic nucleotides may significantly influence myelopoiesis. Furthermore, the results introduce the interesting possibility that stimulation, unlike inhibition, may be initiated through an extracytoplasmic mechanism that does not require direct activation of cytoplasmic cyclic nucleotide-dependent protein kinases.

Animals↗
PubMed1990

Effects of simvastatin and cholestyramine in familial and nonfamilial hypercholesterolemia. Multicenter Group I.

Simvastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was compared with cholestyramine resin in a randomized open-label 12-week multicenter study of 251 high-risk patients with familial or nonfamilial hypercholesterolemia. Simvastatin, 20 mg and 40 mg daily, produced mean reductions in total cholesterol of 26% and 33%, respectively, and reductions in low-density lipoprotein cholesterol level of 32% and 40%. Cholestyramine resin, 4 to 12 g twice daily, reduced total cholesterol and low-density lipoprotein cholesterol levels 15% and 21%, respectively. High-density lipoprotein cholesterol levels were increased 8% to 10% by all treatments. Plasma triglyceride levels were moderately decreased by simvastatin treatment, while triglyceride levels increased with cholestyramine treatment. Simvastatin was better tolerated than cholestyramine, which had numerous gastrointestinal tract side effects. No patient had a serious drug-related adverse event.

Adult↗
PubMed1987

Hypercalcemia can potentiate the nephrotoxicity of Bence Jones proteins.

Hypercalcemia is frequently observed in patients with multiple myeloma and renal failure. Whether Bence Jones protein (BJP) is directly nephrotoxic and how and whether hypercalcemia might contribute to this putative nephrotoxicity is currently unclear. To examine this issue, we studied the effect of modest hypercalcemia on the glomerular filtration rate (GFR) of rats exposed to a BJP that by itself had been found to be nonnephrotoxic. Three groups of rats were studied. All were anesthetized and underwent a baseline measurement of inulin clearance (Cin). After this, group 1 (n = 13) rats were given 2 ml of vehicle (phosphate-buffered saline solution [PBS]) and were then made hypercalcemic with an infusion containing 0.048 mol/L CaCl2. At the end of 2 hours a second Cin was measured. Group 2 rats (n = 8) were given 100 mg BJP in 2 ml PBS and a non-calcium-containing infusate. Group 3 (n = 11) rats were given 100 mg of the BJP in 2 ml PBS and then the calcium-containing infusate used in group 1 rats. Rats in groups 2 and 3 also had a second Cin measured at the end of 2 hours. Renal blood flow was measured with an electromagnetic flow probe. At the completion of the second clearance, kidneys were processed for renal histologic assessment. The serum calcium level measured during the second Cin period was 13.5 mg/dl for group 1, 7.9 mg/dl for group 2, and 13.7 mg/dl for group 3. No significant decrement in GFR was observed in group 1 or 2 rats. In contrast, group 3 rats had a 46% fall in GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Respiratory and calcium transport properties of spiny lobster hepatopancreas mitochondria.

Mitochondria were isolated from the hepatopancreas of the Florida spiny lobster Panulirus argus using a high osmolarity medium containing 600 mM mannitol, 83 mM sucrose, 5 mM 4-morpholinepropanesulfonic acid, pH 7.6, 0.5% bovine serum albumin (BSA), and 1 mM EDTA. O2 uptake and Ca2+ transport were measured by electrode methods in similar media (plus 4 mM KPi, 3.3 mM MgCl2, and 0.67 mg/ml BSA, with 80 mM KCl replacing a portion of the osmotic support). Substrate-supported respiration was observed to be coupled to phosphorylation of ADP or uptake of Ca2+ ions. State 3 rates (nanogram atoms O X minute-1 X milligram protein-1 +/- SEM (N)) were: 49.2 +/- 3.9 (19), succinate; 30.9 +/- 3.9 (6), DL-palmitoyl carnitine; 29.0 +/- 2.7(9), L-malate; 40.0 +/- 2.3(3), L-glutamate; 27.7 +/- 2.2(5), D-3-hydroxybutyrate; and 26.4 +/- 2.4 (18), L-proline +/- pyruvate. alpha-Glycerol phosphate was not oxidized. Ca2+ uptake driven by succinate oxidation proceeded with Ca:O ratios of 4.0 +/- 0.2 (SEM). Hepatopancreas mitochondria were not uncoupled by Ca2+ uptake in excess of 1100 ng atoms X mg protein-1. Ca2+ efflux could be induced by ruthenium red, indicating the presence of an active Ca2+ cycle. These mitochondria may provide a favorable model system in which to study regulation of the Ca2+ cycle.

Animals↗