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Biomedical subjects

E Berger

Publications and source records attributed to E Berger.

At least 127 records · Page 7Linked to original sources
PubMed1988

Neutrophils accentuate ischemia-reperfusion injury in isolated perfused rat kidneys.

The contribution of neutrophils to reperfusion injury after ischemia is not known. To determine the effect of neutrophils on the function of ischemic kidneys, we added purified human neutrophils during perfusion of isolated ischemic or nonischemic rat kidneys. Reperfusion of ischemic kidneys with neutrophils caused a distinct morphological lesion of vascular endothelial and smooth muscle cells and more functional injury than reperfusion with buffered albumin alone; with neutrophils, glomerular filtration rate (GFR) was 113 +/- 7 microliter.min-1.g-1, tubular sodium reabsorption (TNa) was 72 +/- 2%; without neutrophils, GFR was 222 +/- 18 microliter.min-1.g-1; TNa was 90 +/- 2%; both P less than 0.01 vs. reperfusion with neutrophils. In contrast, addition of neutrophils did not injure control kidneys, unless the neutrophil activator, phorbol myristate acetate, was also added. Two experiments suggested that O2 metabolites contributed to neutrophil-mediated injury to ischemic kidneys. First, reperfusion of ischemic kidneys with O2 metabolite-deficient neutrophils from a patient with chronic granulomatous disease did not cause more injury than reperfusion with buffered albumin alone. Second, simultaneous addition of the O2 metabolite scavenger, catalase, prevented the GFR and TNa decreases caused by neutrophils but did not decrease injury in the absence of neutrophils. We conclude that neutrophils by an O2 metabolite-dependent mechanism contribute to ischemia-reperfusion injury in the isolated perfused kidney.

Animals↗
PubMed1988

Ovarian cancer and tumor markers: sialic acid, galactosyltransferase and CA-125.

In an effort to correlate the serum values of potential markers, including CA-125, galactosyltransferase, and total sialic acid, with residual tumor mass after initial surgery, 43 patients with FIGO stage IIb and c, III and IV ovarian cancer were studied. The sensitivity of galactosyltransferase and sialic acid levels was sufficient to correlate their serum values with the corresponding residual tumor mass. Furthermore, 28 patients were histopathologically evaluated for their response to chemotherapy. Determination of these tumor markers did not permit discrimination between small residual disease (less than or equal to 1 cm) and a state of 'no evidence of disease'. Conversely, progression of disease has been associated with a sensitive increase in the level of all three markers. CA-125 has been found to be the most useful of the three for distinguishing between responders and nonresponders.

Antigens, Neoplasm↗
PubMed1988

Managing the medical record on a concurrent basis: facts and possibilities.

In 1987, six Yale graduate students set out to study the concurrent review methods used in key hospitals across the US. They examined the advantages and disadvantages of concurrent review and the tie-in of medical record concurrent review coding with utilization review activities. The first part of their report is published this month, with the conclusion appearing next month.

Abstracting and Indexing↗
PubMed1988

Managing the medical record on a concurrent basis: facts and possibilities. Part 2.

In 1987, six Yale graduate students set out to study the concurrent review methods used in key hospitals across the US. They examined the advantages and disadvantages of concurrent review and the tie-in of medical record concurrent review coding with utilization review activities. The first part of their report appeared in the May issue of JAMRA. The second part appears below.

Abstracting and Indexing↗
PubMed1987

Antiarrhythmic agents diminish thiourea-induced pulmonary vascular protein leak in rats.

Drugs possessing membrane stabilizing activity might act to diminish the augmented microvascular permeability resulting from acute lung injury. To test this rats were pretreated with quinidine, procainamide, or lidocaine and then given the lung injury-inducing agent thiourea. Vascular permeability, assessed as the extravascular accumulation of radiolabeled protein, was increased more than threefold by thiourea. This increase was diminished by 29, 34, and 43% after pretreatment with procainamide, quinidine, and lidocaine, respectively. Lidocaine also returned the thiourea-induced increase in lung wet weight-to-dry weight ratios to control levels. This protection was not likely due to hemodynamic effects of these agents, since no differences were noted in cardiac output between pretreated rats and those receiving thiourea alone and a small increase in mean pulmonary arterial pressure in the lidocaine-pretreatment group was the only difference noted. O2 metabolites have been implicated in the pathogenesis of thiourea-induced lung injury. None of these agents scavenged O2- or H2O2 directly, but quinidine and procainamide diminished in vitro neutrophil O2- and H2O2 production, and lidocaine inhibited neutrophil H2O2 production. However, neutropenia (PMN less than 100/ml) induced with either vinblastine or cyclophosphamide (Cytoxan) failed to prevent thiourea-induced increases in pulmonary vascular protein leak. In conclusion, procainamide, quinidine, and lidocaine diminished lung injury in rats after thiourea. Although these agents diminish PMN O2 metabolite production in vitro their salutary role in thiourea-induced lung injury appears to be through an unknown mechanism that is independent of their effects on neutrophil O2 metabolite-dependent toxicity.

Animals↗
PubMed1987

Stepwise degradation of the hexapeptide Met-Ala-Ser-Pro-Phe-Ala by dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (dipeptidyl-peptide hydrolase, EC 3.4.14.-) purified from pig kidney was proved to split off the N-terminal dipeptide Met1-Ala2 and, subsequently the dipeptide Ser3-Pro4 from the synthetic model peptide Met-Ala-Ser-Pro-Phe-Ala representing the N-terminal part of a signal sequence of leucocyte interferon. The kinetic parameters for the release of Met1-Ala2 (Km 3.2.10(-5) mol.l-1 and Ser3-Pro4 (Km 1.65.10(-4) mol.l-1, kcat57.9 s-1) were determined. The dipeptides Ser-Pro and Phe-Ala were found to be competitive inhibitors of the hydrolysis of Gly-Pro-NHNp by dipeptidyl peptidase IV.

Animals↗
PubMed1986

Sustained efficacy of percutaneous transluminal coronary angioplasty.

To determine whether the immediate efficacy of percutaneous transluminal coronary angioplasty (PTCA) is sustained, follow-up data were obtained in 183 patients who had undergone PTCA at least 1 year earlier. The duration of follow-up ranged from 1 to 5 years. Subjective clinical information was obtained in each patient and objective functional information, determined by exercise stress testing, was obtained in 91. PTCA was initially successful in 141 patients (79%). Of the 42 patients in whom PTCA was unsuccessful, 26 underwent coronary artery bypass graft surgery (CABG), while 16 were maintained on medical therapy (MED). When compared to the MED patients at time of follow-up, successful PTCA patients experienced less angina (13% vs 47%; p = 0.003), used less nitroglycerin (25% vs 73%, p = 0.003), were hospitalized less often for chest pain (8% vs 31%; p = 0.02), and subjectively felt their condition had improved (96% vs 20%; p less than 0.001). Furthermore, during exercise testing, the prevalence of angina was reduced (9% vs 43%; p = 0.05), and exercise duration was greater (8.2 minutes vs 5.8 minutes, p = 0.05) among PTCA patients. There were no significant differences in the incidence of subsequent myocardial infarction, mortality, or need for coronary artery bypass surgery. For these variables, no differences were seen between the CABG and PTCA groups. Thus, successful PTCA results in long-term relief of subjective and objective manifestations of myocardial ischemia, superior to that of medical therapy and comparable to CABG.

Angina Pectoris↗
PubMed1986

Ion transport in rat proximal colon in vivo.

Active Na+ absorption by the rat proximal colon in vivo is for the most part electrically silent. The rheogenic Na+ flux makes up only 8%. To elucidate the underlying transport pathways, the following experimental approaches were used: ion substitution experiments such as choline for Na+, cyclamate for Cl-, variation of luminal pH; administration of known inhibitors; and determination of changes in luminal CO2 tension and pH. The transcolonic ion fluxes as well as the electrical parameters potential difference, specific electrical resistance, and short-circuit current were monitored. Na+ transport was drastically reduced in the absence of luminal Cl-, and vice versa Cl- absorption was blocked at zero Na+. NaCl absorption was blocked by amiloride (10(-3) M) and 4-acetamido-4'-isothiocyanostilbene-2, 2'-disulfonic acid and was lowered by acetazolamide. Colonic NaCl absorption was not influenced by luminal furosemide. Na+ absorption increased with alkalinization of the luminal fluid. Tris instead of HCO-3 buffer at constant pH favored Cl- uptake. The results may easily be explained by the operation of a Na+-H+ antiport functionally coupled to a Cl(-)-HCO-3 antiport. These transport processes are supposed to be present in the columnar cells of the colonic epithelium. There is good evidence for the association of K+ secretion with rheogenic Cl- secretion by the crypt cells.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1986

Developmental changes in the responsiveness of rat kidney to vitamin D metabolites.

Kidneys from both normal and vitamin D-deficient rats were found to show changes in responsiveness to vitamin D metabolites during postnatal development, correlated with the concentrations of the specific receptor for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or the specific binding protein for 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3]. Cytosol preparations from kidneys of vitamin D-deficient rats, in the second week of life, contained specific binding proteins for 24,25-(OH)2D3. From the fourth week of life, specific receptors for 1,25(OH)2D3 were predominant. In the third week after birth, both the receptor for 1,25(OH)2D3 and the 24,25(OH)2D3 binding protein were present. We have used a sensitive parameter for vitamin D action, the stimulation of creatine kinase BB (CKBB) activity, to measure the response of kidneys from vitamin D-deficient or normal rats. In the first days of life of vitamin D-deficient rats, the kidneys did not respond to either vitamin D metabolite; in the second week of life, there was stimulation of renal CKBB only by 24R,25(OH)2D3; beginning in the fourth week of life, only 1,25(OH)2D3 stimulated renal CKBB. However, during the third week of life, CKBB activity was increased by both metabolites. In normal animals, which showed a lower CK activity at all ages, the response was similar to that in vitamin D-deficient animals but the peak was achieved a few days later. The stimulation of CKBB by vitamin D metabolites occurred in all the zones of the kidneys. An increase in renal CKBB by 1,25(OH)2D3 was also detected immunohistochemically. The increase of CKBB activity caused by the two vitamin D metabolites at different stages of development, closely correlated with changes in the presence of the 1,25(OH)2D3 receptor or the 24,25(OH)2D3 binding protein, suggests a specific role for each metabolite during renal development.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Determination of rheogenic ion transport in rat proximal colon in vivo.

A direct clamping technique is demonstrated, which allows monitoring of rapid changes of the short-circuit current (Isc) and the specific transepithelial resistance (Rm) as well as measurement of ion fluxes under short-circuit conditions in vivo. Due to the cylindrical symmetry of the colon the intraluminal electrode was devised as a centrally fixed silver rod, by which radial current injection was achieved. The geometrical arrangement of the electrodes guaranteed zero potential difference (PD) along the whole axis of the colon segment. The Isc was determined to 3.3 +/- 0.7 mueq h-1 cm-2 and Rm equal to 121 +/- 5 omega cm2. These data obtained by direct short-circuiting agree well with our earlier Rm and Isc data based on cable analysis, where the Isc was calculated from the open-circuit PD and Rm. This is considered as evidence for the reliability of the two independent in vivo techniques. Their validity was confirmed by the expected effects of drugs acting on rheogenic ion transport. Both the indirect (via Rm) as well as the direct Isc determination may be used alternatively as required; one may serve to match the other. For larger tubular structures like the rat colon the direct clamping should be preferred as the standard procedure for the Isc determination in vivo.

Alprostadil↗
PubMed1984

Conformational specificity of chymotrypsin toward proline-containing substrates.

A number of peptide-4-nitroanilide substrates containing proline within the peptide chain have been synthesized and subjected to chymotryptic hydrolysis. Values of kcat and Km have been obtained from measurements at pH 7.8 and 25.0 degrees C. Kinetic studies at high enzyme concentrations up to 6.0 X 10(-4) mol X 1(-1) have allowed the evaluation of the conformational specificity of chymotrypsin due to the observation of various kinetic phases during the time-course of the reaction. When proline occupies the P2 position within the peptide chain, it is shown that the enzyme cleaves only the trans isomer of the substrate. The conformational specificity has also been studied for proline in P4 and P5 positions of the substrate. In some cases, an enzyme-catalyzed hydrolysis of the cis isomer was detected. From the amplitude ratios and the rate constants of the kinetic phases, information about the structural dependency of the cis/trans interconversion could be obtained. Charged residues N-terminal to the isomeric bond are of little influence on either cis/trans ratio or the rate of cis to trans interconversion. Extending the peptide chain N-terminal to the isomeric bond by alanine decreases to a low extent the cis content and increases the rate constant of the trans isomer formation.

Aniline Compounds↗
PubMed1984

Determination of short-circuit current in the in vivo perfused rat colon.

Current pulses (I) were injected into the lumen of proximal colonic segments in vivo, and the corresponding voltage deflections (delta PD) superimposed on the transcolonic PD were recorded. From the exponential decay of delta PD along the colon axis, the electrical length constant (lambda) was determined. Based on cable analysis the input resistance (= delta PD x = 0/I) and lambda made it possible to calculate the specific resistance (Rm) of the colonic epithelium as 128 +/- 16 omega X cm2. As Rm proved to be an ohmic resistor, the extrapolation from open-circuit PD (8-12 mV, lumen negative) to zero PD was feasible and made the calculation of short-circuit current (= PD/Rm) equal to 70 +/- 16 microA/cm2. In the presence of amiloride short-circuit current decreased to about 50%, whereas with theophylline it increased by about 30%. Substitution of luminal Na+ with choline or Cl- with cyclamate was associated with a marked increase of Rm. The rheogenic component of net Na+ transport was estimated to be only 8%. Electroneutral Na+ absorption functionally coupled with Cl- absorption displayed the characteristic feature of ion transport in the rat proximal colon.

Animals↗