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J I Hirsch

Publications and source records attributed to J I Hirsch.

At least 19 recordsLinked to original sources
PubMed1994

Premicellar taurocholate enhances calcium uptake from all regions of rat small intestine.

BACKGROUND/AIMS: The specific components of bile, which is necessary for normal calcium absorption, are unknown. We have previously shown that Ca2+ is bound with high affinity by premicellar taurocholate. The current studies examined the effects of taurocholate on intestinal calcium transport. METHODS: Intestinal Ca2+ uptakes were measured from proximal, mid, and distal small intestinal segments perfused with solutions containing 45CaCl2 (0.1-1 mmol/L), taurocholate (0-10 mmol/L), trihydroxymethylaminomethane buffer (pH 7), phenolsulfonpthalein (nonabsorbable marker), and NaCl (total ionic strength, 0.16 mol/L) for four randomized perfusion periods. In other studies, the proximal small intestine was divided into two equal segments and perfused with either 45CaCl2 or 45CaCl2 plus taurocholate (2.5-5 mmol/L). Calcium absorption was measured from the difference in uptake and calcium concentration retained in mucosa. Finally, effects of taurocholate on Ca2+ uptake across isolated brush border membrane vesicles were measured. RESULTS: Premicellar taurocholate produced an approximately 1.7-2-fold enhancement (P < 0.01) in Ca2+ uptake in all regions, with lesser contributions from micellar taurocholate. These effects resulted in a net increase in calcium absorption. Premicellar taurocholate also significantly increased calcium uptake across brush border vesicles. CONCLUSIONS: Premicellar taurocholate significantly enhances calcium uptake into, and absorption across, enterocytes. The mechanisms remain to be experimentally verified.

Animals↗
PubMed1994

Evidence that bile salts are important for iron absorption.

The role of bile salts in intestinal Fe absorption has not previously been defined. We have recently shown that bile salts having cholanic ring 7 alpha-OH and/or 12 alpha-OH groups bind Fe2+ with high affinity at premicellar concentrations and also produce a two-to threefold enhancement in Fe2+ uptake from perfused intestinal segments in vivo. However, the physiological relevance of these observations for Fe2+ absorption was not known. To study this, we examined the effects of a single dose of taurocholate (TC) administered with 59Fe-FeSO4 in reversing iron malabsorption induced by bile duct ligation. Fe absorption from three 0.5-mg doses of 59Fe-FeSO4 was measured from five groups of six adult Sprague-Dawley rats each: group 1, before and after bile duct ligation and subsequent administration of 59Fe-FeSO4 + TC test dose; group 2, before and after bile duct ligation followed by a third dose of Fe alone; group 3, before and after bile duct ligation followed by a third dose of Fe+taurodehydrocholate (TDHC); group 4, sham laparotomy; and group 5, nonoperated controls where Fe absorption was measured from three doses of 59Fe-FeSO4 at the same time intervals as group 1. Absorption was measured, using whole body counting, after achievement of steady-state counts after each Fe dose. Mean percentage absorption from dose 1 (baseline) was 35.33 +/- 4.6% (SE). No significant differences between any groups were noted. In nonoperated controls (group 4), Fe absorption was virtually identical after all three doses. Also, hematocrit did not change in any of the 30 animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

High-affinity binding is essential for enhancement of intestinal Fe2+ and Ca2+ uptake by bile salts.

Both calcium and iron are bound with high affinity by premicellar bile salts having cholanic ring 7-OH and/or 12-OH groups, forming soluble cation-bile salt complexes. The authors of the current study recently showed that premicellar taurocholate markedly enhances intestinal iron and calcium uptake. However, the relationship of high-affinity binding to the observed uptake enhancement was unknown. In the current study, this relationship was examined by studying taurodehydrocholate (TDHC) binding and intestinal uptake of both cations. Ca2+ binding was measured by noting depression of [Ca2+] activity in solutions containing constant total Ca concentrations (1 mmol/L) and varying [TDHC] (0.5-50 mmol/L). Fe2+ binding was assessed by equilibrium dialysis studies of 59FeSO4 (0.179-1.79 mmol/L) and TDHC (0.5-50 mmol/L). Effects of TDHC on intestinal Fe2+ and Ca2+ uptake were measured in isolated perfused intestinal segments in vivo in seven and eight Sprague-Dawley rats, respectively. TDHC, lacking ring OH groups, did not bind either cation with high affinity and had no effect on their intestinal uptake. These results suggest that high-affinity binding is essential for bile salt-induced enhancement of intestinal Fe2+ and Ca2+ uptake.

Animals↗
PubMed1992

Increased morbidity with increased pulmonary albumin flux in sepsis-related adult respiratory distress syndrome.

OBJECTIVE: To determine the feasibility of utilizing a scintigraphic technique to differentiate patients with adult respiratory distress syndrome due to sepsis syndrome from control volunteers and patients with congestive heart failure. Gamma scintigraphy was compared with chest roentgenograms to predict mortality rate and morbidity in adult respiratory distress syndrome (ARDS) patients. DESIGN: Prospective study. SETTING: University hospital ICUs. PATIENTS: Thirty-five control volunteers, 19 patients with congestive heart failure, 30 patients with a diagnosis of sepsis. MEASUREMENTS AND MAIN RESULTS: All patients were infused iv with technetium 99m-labeled albumin and underwent computerized gamma-scintigraphic analysis with a portable gamma camera. Lung-to-heart ratio of tracer was calculated and expressed as the slope index. Increase in slope index indicated increased pulmonary albumin flux. Slope index was no different in controls compared with congestive heart failure patients, unless the pulmonary artery occlusion pressure (PAOP) was greater than 30 mm Hg. Patients with a diagnosis of sepsis had an overall increased slope index compared with the other groups. A subgroup of patients in the septic group had a normal slope index. Septic patients with an increased slope index had a significantly (p less than .01) longer duration of mechanical ventilation (36 +/- 5 vs. 7 +/- 1 days), spent longer in the ICU (67 +/- 9 vs. 11 +/- 1 days), and had a longer hospital stay (113 +/- 20 vs. 35 +/- 5 days) than septic patients with a normal slope index. CONCLUSIONS: Gamma scintigraphy successfully differentiated between control volunteers and patients with congestive heart failure with PAOP less than 30 mm Hg from patients with sepsis-induced ARDS. Although all of the patients with a clinical diagnosis of septic ARDS had similar impairments in oxygenation and chest roentgenograms, those patients with a significantly increased pulmonary albumin flux (greater than 2 SD above control mean) had a markedly increased morbidity.

Adult↗
PubMed1992

Clearance of 131I by hemodialysis.

There are no available data documenting the dialysis clearance of iodide in humans. This work quantitates the hemodialysis clearance of iodide (as 131I) over time and examines certain factors which influence that clearance. In a single-patient study, three dialysis periods were studied over the 24 to 96 hours following administration of 129 mCi 131I given as Na131I. Hemodialysis clearance of 131I was calculated both from the arterio-venous difference of 131I across the artificial kidney and the appearance of 131I in the expended dialysate. Calculations were based on 131I activity in whole blood, whole plasma, and the supernate of plasma treated with 10% trichloroacetic acid (TCA). The hemodialysis clearance of 131I was highest when calculated from the activity of the plasma supernate, 171.3 +/- 6.0 ml/min for the period 24-29 h. post dosing, and fell in a linear fashion with time. The clearance calculated from whole blood activity was always intermediate to that from whole plasma (lowest) or the plasma supernate (highest). The percentage of plasma 131I activity precipitated by TCA rose over the study period and displayed a strong negative correlation to the hemodialysis clearance of 131I. The hemodialysis clearance of iodide, as 131I, is on the order expected for a free ion and is 4-5 times higher than the endogenous renal clearance of the ion. However, the calculated clearance varies with respect to total time of dialysis and the fraction of blood in which the 131I activity is measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1991

Differentiation of reperfused-viable (stunned) from reperfused-infarcted myocardium at 1 to 3 days postreperfusion by in vivo phosphorus-31 nuclear magnetic resonance spectroscopy.

Thrombolytic therapy has increased the need for a technique to assess the viability of recently reperfused myocardium. This study examined the ability of in vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy to distinguish reperfused-viable (stunned) from reperfused-infarcted myocardium at 6, 30, and 54 hours following coronary artery occlusion in a canine model. A 15-minute occlusion produced reperfused-viable myocardium in five animals and a 360-minute occlusion produced reperfused-infarcted myocardium in six animals. Postreperfusion risk zone myocardial phosphocreatine (PCr) concentration measured by P-31 NMR spectroscopy was significantly depressed throughout the 3-day study period in infarcted but not in viable myocardium (p less than 0.01 between groups, all time points). The postreperfusion ratio of inorganic phosphate (Pi) to PCr concentration, as determined by NMR spectroscopy, was elevated throughout the study period in infarcted but not in viable reperfused myocardium (p less than 0.01 between groups, all time points). Postreperfusion Pi concentration was elevated at 6 hours but not subsequently in reperfused-infarcted myocardium, and was not elevated in reperfused-viable myocardium. Logistic regression models selected PCr concentration and the Pi/PCr ratio as providing the best discrimination between reperfused-viable and reperfused-infarcted myocardium. The accuracy of P-31 NMR variables selected by logistic regression analysis for determining myocardial viability ranged from 97% to 100%.

Animals↗
PubMed1991

Effect of brief regional ischemia followed by reperfusion with or without superoxide dismutase and catalase administration on myocardial sarcoplasmic reticulum and contractile function.

The effect of reperfusion with and without free radical scavengers on sarcoplasmic reticulum and contractile function was examined in a canine model of 15-minute coronary artery occlusion followed by reperfusion. Dogs were reperfused with (n = 13) or without (n = 16) superoxide dismutase and catalase or were killed at 15 minutes of ischemia (n = 17). Superoxide dismutase and catalase were administered as a bolus (20,000 and 12,500 U/kg, respectively) beginning 1.25 minutes before reperfusion followed by infusion of 16,000 and 12,500 U/kg/hr, respectively. Sarcoplasmic reticulum function was evaluated from the rate of calcium uptake of unfractionated subepicardial, subendocardial, and transmural homogenates determined with and without ruthenium red to close the calcium release channel. Mechanical function was evaluated by means of sonomicrometry. Fifteen minutes of ischemia significantly (p less than 0.05) depressed the sarcoplasmic reticulum calcium uptake rate only in the subendocardium (from 25 +/- 2 to 14 +/- 1 nmol/min/mg without ruthenium red and from 60 +/- 3 to 49 +/- 3 nmol/min/mg with ruthenium red). Reperfusion with or without superoxide dismutase and catalase restored homogenate calcium uptake rates to normal, although severe contractile dysfunction persisted. This indicates that damage to the sarcoplasmic reticulum may not be the major cause of postreperfusion contractile dysfunction. Ischemia-reperfusion caused a decrease in systolic shortening from 19 +/- 2% to 1 +/- 2% with and from 18 +/- 1% to 4 +/- 1% without free radical scavengers (p = NS between groups). Thus administration of superoxide dismutase and catalase beginning shortly before reperfusion had no effect on postreperfusion contractile dysfunction or sarcoplasmic reticulum function.

Animals↗
PubMed1991

Premicellar taurocholate enhances ferrous iron uptake from all regions of rat small intestine.

Inorganic iron is virtually insoluble at the pH of small intestinal contents. This severe solubility limitation has been partly overcome by intraluminal substances that bind and solubilize iron, thus increasing availability for absorption. While several dietary ligands capable of solubilizing Fe2+ in intestinal lumen have been described, an endogenous binding ligand has not been previously described. It has recently been shown that certain trihydroxy bile acids (taurocholate and glycocholate) show high-affinity premicellar and low-affinity micellar Fe(2+)-binding properties, resulting in the formation of soluble Fe(2+)-bile salt complexes. It was hypothesized that this binding would increase the intraluminal pool of soluble iron, increase delivery of soluble iron to mucosal carriers, and thus enhance intestinal Fe2+ uptake. As a first step toward testing this hypothesis, the effect of taurocholate on Fe2+ uptake from all regions of in vivo rat small intestine is reported. It is shown that taurocholate, at premicellar concentrations, produces a marked, stepwise increase in Fe2+ uptake from all regions of small bowel, with little further increase above the critical micellar concentration. Enhancement of intestinal Fe2+ uptake is a newly described effect, and potential physiological function, of premicellar bile salts.

Animals↗
PubMed1991

Platelet-activating factor in porcine Pseudomonas acute lung injury.

We investigated the role of platelet-activating factor (PAF) in acute septic lung injury by examining the effects of the selective PAF antagonist SRI 63-675 and by measuring PAF in lung tissue in the porcine model. Four groups of pigs (15-25 kg) were studied: saline control (C, n = 5); Pseudomonas (Ps, n = 9), given 5 x 10(8) CFU/ml at 0.3 ml/20 kg/min intravenously over 1 hr; SRI (n = 3), given SRI 63-675 in a 40 mg/kg bolus; and SRI + Ps (n = 5). Ps infusion produced a fulminant lung injury characterized by a threefold increase in pulmonary arterial pressure at 30 min and persistent pulmonary hypertension (P less than 0.05 vs C), a significant (P less than 0.05 vs C) decrease in arterial oxygen tension (PaO2) from 60 min, a significant (P less than 0.05 vs C) increase in extravascular lung water (EVLW) from 120 min, and a significant (P less than 0.05 vs C) increase in albumin flux determined scintigraphically as slope index at 150-180 min. Systemic arterial pressure and cardiac index (CI) decreased significantly (P less than 0.05) in the Ps group vs C at 60 and 180 min, respectively. Bolus injection of SRI 63-675 at the time of Ps infusion blocked the early pulmonary hypertension, attenuated the early and late fall in PaO2, ameliorated the increase in EVLW, and prevented the late (150-180 min) increase in albumin flux. SRI 63-675 had minimal effects on Ps-induced hypotension or alterations in CI.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1990

Persistent splenic visualization on technetium-99m DISIDA hepatobiliary studies.

Tc-99m DISIDA is widely used for studying a variety of biliary conditions. It is generally recognized that the spleen is normally visualized on DISIDA imaging only during the blood pool phase. Upon review of our experience with DISIDA, visualization of the spleen was found more common than generally acknowledged. All DISIDA examinations performed at our two institutions were retrospectively reviewed; 95 studies were performed at Institution #1 and 150 studies at Institution #2. There were 138 men and 107 women. Quality control to confirm radiochemical purity included sephadex gel column chromatography. Of 245 patient studies, persistent splenic visualization was identified in one patient (1.0%) at Institution #1 and in 11 patients (7.3%) at Institution #2. There was no correlation between age, sex or final diagnosis and persistent visualization of the spleen. It is suggested that persistent splenic visualization may be caused by an elevated concentration of reduced hydrolized technetium (colloid) in DISIDA.

Biliary Tract Diseases↗
PubMed1990

Pulmonary compliance: early assessment of evolving lung injury after onset of sepsis.

We compared the sensitivity of dynamic (Cdyn) and static lung compliance (CL) with indicators of permeability injury in a model of septic porcine adult respiratory distress syndrome. Two groups of anesthetized ventilated swine (15-25 kg) were studied. Septic animals (Ps, n = 13) received Pseudomonas aeruginosa intravenously for 1 h, which resulted in severe adult respiratory distress syndrome. Controls (C, n = 13) received 0.9% NaCl. Cdyn, CL, bronchoalveolar lavage for protein estimation, and thermal cardiogreen extravascular lung water (EVLW) measurements were performed in seven C and eight Ps animals. Six C and five Ps animals underwent gamma camera measurement of lung-to-heart ratio (slope index) of 99Tc-labeled human serum albumin. Both Cdyn and CL decreased significantly (P less than 0.01) at 30 min and thereafter in Ps vs. C. EVLW, slope index, and bronchoalveolar protein content increased significantly (P less than 0.05) in Ps vs. C at 120, 150, and 300 min, respectively. Cdyn and CL decreased well before onset of permeability injury. These early changes may be due to release of vasoactive mediators and sequestration of neutrophils in the pulmonary capillaries and later to increases in EVLW. Measurement of Cdyn and CL represents an early means of assessing evolving lung injury in this acute septic porcine model.

Animals↗
PubMed1990

Assessment of the dynamics of allograft rejection utilizing Tc-99m labeled lymphocytes.

The feasibility of utilizing technetium 99m (Tc-99m) lymphocytes labeled by a modified stannous chloride technique for the assessment of cardiac allograft rejection was examined. Syngeneic lymphocytes were labeled with Tc-99m at 125 microCi per 10(7) cells. Mean labeling efficiency was 67 +/- 17%, n = 44. Two groups of rats allogeneic (ALLO) (ACI/Lewis) and syngeneic (SYN) (Lewis/Lewis) were injected with labeled cells at two, four, five, and seven days post cardiac graft. At 20 hr post-injection, transplant and native hearts were harvested for radioanalysis and histology. Ratio of percent dose per gram transplant heart to native heart (T/N) revealed a significant difference between ALLO (T/N = 2.7 +/- 0.23, n = 5) and SYN (T/N = 1.73 +/- 0.12, n = 5) at two days P[F] = 0.0045. Maximum difference occurred at five days with ALLO mean T/N of 6.40 +/- 0.54, n = 5 (P[F] = 0.0001). There was no significant difference at seven days post graft with ALLO 2.85 +/- 0.30, n = 5 and SYN 2.02 +/- 0.05, n = 5 (P[F] = 0.0166). SYN rat T/Ns did not change significantly (mean 1.83 +/- 0.10, n = 18) at the various time periods.

Animals↗
PubMed1990

Evaluation of technetium-99m disofenin by column and instant thin-layer chromatography: demonstration of radiocolloid as a cause for splenic uptake.

We found persistent splenic uptake in 5% of patients undergoing hepatobiliary imaging with Tc-99m Disofenin when administered within a few minutes after labeling, suggesting the presence of radiocolloid. Hydrolyzed reduced Tc-99m colloid (HR-Tc) present in labeled Disofenin kits is controversial and may be dependent on method of assay and radiochemical kinetics. Kits were therefore evaluated by gel column (GCC) and instant thin-layer (ITLC) chromatographic methods. Tc-99m Disofenin was prepared according to the manufacturer's instructions and was maintained at room temperature (23 degrees C) or was incubated at 37 degrees C for 0.5 hr and then held at 23 degrees C. Aliquots were obtained at intervals over 5 hr and applied to Sephadex G-15 resin columns and ITLC-SG strips, with distilled water as mobile phase. GCC showed 14.9% +/- 3.4% and 11.0% +/- 2.9% initial values of HR-Tc at 23 degrees C and 37 degrees C treatments, respectively. HR-Tc decreased over time with each treatment. ITLC showed 1.2% +/- 0.4% and 1.3% +/- 0.2% HR-Tc, with no change over time. ITLC appears to be an insensitive method for the detection of HR-Tc. Incubation of Tc-99m with Disofenin kits for 30 min at 37 degrees C or for 1 hr at 23 degrees C offers an empiric method to ensure HR-Tc levels acceptable for nuclear imaging.

Chromatography, Gel↗
PubMed1990

Premicellar taurocholate avidly binds ferrous (Fe++) iron: a potential physiologic role for bile salts in iron absorption.

Two of the major divalent cations in human physiology, Ca++ and Fe++, are poorly soluble at the pH of intestinal contents, and active "uphill" transport mechanisms exist for both ions in proximal small intestine. We have recently demonstrated significant binding of Ca++ to both premicellar and micellar bile salts and have postulated that high-affinity premicellar binding involves interposition of Ca++ between terminal carboxyl (COO-) and 7-OH or 12-OH groups of the steroid ring. The present studies were made to determine whether such binding extends to other divalent cations, and specifically to Fe++, which, like Ca++, has a hydrated diameter of 6 A. Equilibrium dialysis studies of sodium taurocholate were made at 25 degrees C with solutions containing 0.5 to 150 mmol/L taurocholate and 0.018 to 1.8 mmol/L iron 59-labeled FeSO4 at pH 3.0 to 6.3 and a total ionic strength of 0.15 mol/L. In control (saline dialysand) cells, [Fe++] was virtually equal in dialysands and dialysates within 5 hours. In sharp contrast, taurocholate-containing dialysands showed significantly higher counts than dialysates, indicating Fe++ binding to taurocholate, independent of pH and Fe concentration. After correction for taurocholate-induced Gibbs-Donnan effects across the membrane, the apparent taurocholate affinity constant (K'f) for Fe++ in micellar solutions (5 to 150 mmol/L) was essentially constant at about 3.1 (mol/L)-1, then increased dramatically below the critical micellar concentration to greater than 100 (mol/L)-1 at [taurocholate] = 0.5 mmol/L. The hyperbolic rise in K'f below the critical micellar concentration is similar to that which we have previously reported for Ca++, indicating significant high-affinity binding of Fe++ to premicellar taurocholate anions and low-affinity binding to micellar anions. It is postulated that Fe++ binding, particularly by premicellar bile salts, may play an important physiologic role in increasing iron solubility within the intestinal lumen, thus increasing iron absorption. The possible role of bile salts in increasing divalent cation solubility and absorption from the intestine is a new field of bile acid research.

Bile Acids and Salts↗
PubMed1989

Significance of alteration in biodistribution of labeled lymphocytes exposed to stannous ion.

The biodistribution patterns of 99mTc (99mTc-lymph) and 111In-lymphocytes with [111In-(Sn)-lymph] or without (111In-lymph) stannous ion treatment was compared in Lewis rats. Syngeneic lymphocytes were labeled with either 125 microCi (4.63 MBq) 99mTc or 5 microCi (185 kBq) 111In per 2 x 10(7) cells. Mean labeling efficiency for 99mTc and 111In was 68.61% +/- 3.90% (SEM) and 87.22% +/- 2.01% (SEM) respectively. 99mTc-lymph (n = 4), 111In-lymph (n = 6) and 111In-(Sn)-lymph (n = 6) rats received 2 x 10(7) cells and were killed 18 h later. While 99mTc-lymph demonstrated significantly less localization in spleen, lymph nodes, and blood (P(F) less than 0.01) as compared with 111In-lymph, 111In-(Sn)lymph also demonstrated a significant difference (P[F]= 0.0001) in lymph node accumulation when compared to 111In-lymph. As the activity levels utilized are not associated with cell radiation damage, these alterations in biodistribution do not reflect viability or chromosomal damage, but appear related to stannous ion exposure.

Animals↗
PubMed1989

Effect of methylene blue on estrogen-receptor activity.

Methylene blue in a 1% sterile solution for injection to help localize occult breast tumor was shown to interfere with the estrogen-receptor protein (ERP) binding-capacity assay. Cytosols derived from ERP-positive lyophilized powders and human breast tissue were evaluated with and without varying levels of treatment with methylene blue. Cytosols treated with 0.1% methylene blue, a clinically significant level, demonstrated a substantially lower ERP binding capacity compared with control cytosols. This alteration was found to be due to a reduction in specific binding capacity and not to an alteration in apparent cytosol protein concentration. The use of methylene blue for occult breast tumor localization is not recommended when an ERP binding-capacity assay is anticipated.

Biopsy, Needle↗
PubMed1989

Noninterference of isosulfan blue on estrogen-receptor activity.

Because a 1% sterile solution of methylene blue used for occult breast tumor localization has been shown to interfere with the estrogen-receptor protein (ERP) binding-capacity assay, isosulfan blue in a 1% injection was studied as a potential alternate stain. Cytosols derived from ERP-positive lyophilized powders and human breast tissue were evaluated with and without varying levels of treatment with isosulfan blue. No modification of the ERP-specific binding capacity was found with this stain. The use of isosulfan blue for localization of occult breast tumor is suggested when an ERP binding capacity assay is anticipated.

Biopsy, Needle↗