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J Stulc

Publications and source records attributed to J Stulc.

At least 19 recordsLinked to original sources
PubMed2000

Distensible transtrophoblastic channels in the rat placenta.

Paracellular pathways in the haemotrichorial placenta of the rat were studied by electron microscopy using lanthanum hydroxide as an electron dense marker. Near term placentae were dually perfused in situ, adding lanthanum to the fetal perfusate. In some placentae outflow pressure on the fetal side was elevated (between 10 and 25 cm H(2)O) to promote filtration of fluid in a fetomaternal direction. Under normal pressure conditions lanthanum particles lined the subendothelial spaces and tubular structures in the inner, syncytial layer of trophoblast. Further penetration of lanthanum into the tubules was blocked by coarse lanthanum aggregates. Elevated fetal hydrostatic pressure resulted in a fluid shift across the placenta (filtration rate 50+/-16 per cent of fetal arterial inflow rate), distending the tubules in the inner trophoblast layer. Lanthanum particles gradually appeared in tubular structures in the middle (syncytial) layer and in the lateral intercellular spaces in the outer (cellular) layer. Finally lanthanum reached the maternal surface of the trophoblast. These pressure effects were only partially reversible. When the fetal pressure was returned to control values, some distension of the tubules persisted and the entire length of the paracellular pathways remained accessible to lanthanum. It is concluded that the placental barrier in the rat contains pressure dependent paracellular pathways connecting the maternal and fetal extracellular compartments.

Animals↗
PubMed1997

Placental transfer of inorganic ions and water.

There are great interspecies differences in placental structure as well as in permeability properties of the placenta. In all species, however, the placenta behaves like a low-permeability barrier containing specific mechanisms of transcellular transport for minerals and other substrates for fetal growth and metabolism. The minerals that are contained in plasma in low concentrations and that are mainly intracellular or sequestered in bones (K+, Mg2+, Ca2+, phosphate) are transported to the fetus actively. The transfer of the main extracellular ions, Na+ and Cl-, exhibit great interspecies differences. In the sheep, the transfer rates of Na+ and Cl- to the fetus are consistent with passive transfer mechanisms. In the rat, Na+ is transported to the fetus actively and the transfer of Cl- is facilitated by a carrier and/or a channel. Transfer of minerals to the fetus is controlled by a variety of mechanisms ranging from very simple ones depending on intrinsic properties of the transport systems to complex mechanisms of hormonal control. Water is presumed to move across the placenta passively. The transfer may be facilitated by the 28-kDa water channel-forming integral protein (CHIP28), which is expressed in the trophoblast syncytium.

Animals↗
PubMed1996

Maternal-fetal potential difference in the rat is generated by the placenta.

Electrical potential difference, PD, was recorded between maternal blood on one side and uterine lumen (transuterine PD), amniotic fluid (amniotic fluid PD), or vitelline blood of the fetus (maternal-fetal PD) on the other side in rats on day 21 of gestation. The values obtained are 2.4 +/- 6.0 mV (mean +/- s.e.), 11.3 +/- 4.5 mV and 9.6 +/- 4.1 mV, respectively. Maternal-fetal PD recorded over a period of 12 min decreased slowly. It increased transiently when the placenta was separated from the uterus, then it decreased more rapidly than in the corresponding controls afterwards. Maternal-fetal PD did not change significantly when the sac of fetal membranes containing the fetus was exposed intact from the uterus. In other experiments the PD was recorded in vitro between vitelline blood of the fetus which had been removed from the uterus together with intact sac of fetal membranes and a bath of Ringer solution. The PD recorded when only the exposed surface of the placenta (the surface by which the placenta had been attached to the uterus) was immersed in Ringer fluid, was the same as that recorded earlier between maternal and fetal blood in the same fetus. The PD decreased rapidly when the placenta was cooled, and it increased again when the placenta was rewarmed. The PD decreased to near 0 mV when the whole sac of fetal membranes was immersed in Ringer. On the basis of these observations it is concluded that the maternal-fetal PD in the rat is generated by the placenta.

Amniotic Fluid↗
PubMed1996

Placental transfer of phosphate in anaesthetized rats.

Mechanisms of transfer of inorganic phosphate, Pi, across the placenta of rats at 21 days of gestation were studied using 32Pi. In one group of experiments the unidirectional transfer of Pi from mother to fetus was estimated from radioactivity in the fetus at various intervals after the tracer injection into the mother. At 15 min after tracer injection, the transfer rate was only slightly higher than the estimated rate of fetal accretion of Pi, and it decreased rapidly with the length of the experiment suggesting deterioration of the transfer mechanism under conditions of an acute experiment. In other experiments, transfer of 32Pi and 51Cr-EDTA (a marker of paracellular transfer) were measured across the dually-perfused placenta in the maternal-fetal direction. The transfer rate of 32Pi was an order of magnitude higher than the transfer of 51Cr-EDTA indicating that most of the Pi transfer is transcellular. The transfer of 32P decreased when the concentration of Na+ in the maternal perfusate was reduced, it was related inversely to the concentration of Pi on the fetal side of the placenta, and it was related directly to the concentration of Ca2+ on the fetal side. The maternal-fetal transfer of Pi exhibited saturation kinetics with a K(m) of about 0.4 mM suggesting that at a physiological concentration of Pi in maternal plasma the transfer mechanism is nearly saturated. The present observations are consistent with Pi being transferred in contransport with Na+. The maternal-fetal transport of Pi appears to be stabilized by the high affinity of the transport system to Pi, and controlled by a negative feedback between fetal concentration of Pi and the Pi transfer rate. It may also be controlled, to some degree, by the fetal plasma Ca2+.

Animals↗
PubMed1996

Effect of NaCl load administered to the fetus on the bidirectional movement of 51Cr-EDTA across rat placenta.

A hypothesis that, in the rat, fluid circulates across the placenta, with circulation being maintained by active transport of Na+ from mother to fetus, has been tested. Transfer of 51Cr-EDTA from mother to fetus and from fetus to mother has been measured and the respective unidirectional transfer constants, Kmf and Kfm, have been calculated. Immediately before the transfer measurement, the fetuses were injected intravenously with 10 microliters of isotonic glucose (controls); with 30 or 300 microliters of isotonic saline; or with 10, 30, or 60 microliters of 9% NaCl. In controls, Kmf of 51Cr-EDTA was 2.0 +/- 0.6 microliters/min, and Kfm was 4.3 +/- 1.0 microliters/min. Injecting the fetus with NaCl had no effect on Kmf, whereas the Kfm was increased significantly in a dose-dependent way. In other experiments, 51Cr-EDTA was injected into nephrectomized maternal animals, and the radioactivity of maternal and fetal plasma was followed for 30 h. The time course of fetal plasma radioactivity supported the thesis that the transfer of 51Cr-EDTA across the rat placenta is highly asymmetrical.

Animals↗
PubMed1996

Transfer of Cl- across placenta of anesthetized rat.

The mechanisms of Cl- transfer across the rat placenta have been investigated. Clearance across the intact placenta from mother to fetus (m-->f) of 51Cr-EDTA (paracellular diffusion marker) and 36Cl- (Kmf) was 1.9 +/- 0.1 and 37.3 +/- 4.1 microliters/min, respectively (mean +/- SE, n = 10), the large difference indicating that most m-->f transfer of Cl- is transcellular. The clearance of 36Cl- across the dually perfused placenta in m-->f and fetal-to-maternal directions was symmetrical and highly sensitive to the anion-exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.1 mM). The Kmf of 36Cl- was not inhibited by anoxia and had a low temperature quotient (Q10 between 32 and 37 degrees C was 1.52). The m --> f transfer of Cl- seemed to be fully saturated at physiological concentrations of Cl-. 36Cl- could be displaced from the transporter on the maternal side by other anions with the following order of affinity: Cl- approximately NO3- > Br- > lactate- >> gluconate. It is concluded that most of the Cl- transfer across the rat placenta is effected by an anion exchanger.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Mechanisms of the fetomaternal transfer of Na+ across the dually perfused placenta of the rat.

In order to investigate mechanisms of fetal-maternal (F-M) transfer of Na+, clearance of 22Na+ and 51Cr-EDTA was measured simultaneously across the dually perfused placenta of the rat. In eight experiments clearance was measured successively in the F-M (Kfm) and in the maternal-fetal (M-F; Kmf) directions. Clearance of 22Na+ in the two directions was approximately equal (Kmf = 11.6 +/- 2.0 microliters/min; Kfm = 11.1 +/- 1.7 microliters/min: mean +/- s.d.) while Kfm of 51Cr-EDTA (4.4 +/- 0.7 microliters/min) was nearly double Kmf (2.4 +/- 0.8 microliters/min) for this tracer. Even greater asymmetry in the transfer of 51Cr-EDTA was found when measured across intact (non-perfused) placenta. It is suggested that this asymmetry is caused by volume flow in the F-M direction. In other experiments transfer was measured in the F-M direction only. Ouabain (0.1 mM) on the maternal side and reduced concentration of Na+ (25 mM) on the fetal side had no effect on the F-M transfer of the tracers. Reducing the temperature of the preparation by 5 degrees C significantly decreased transfer of 22Na+. The transfer of 22Na was inversely related to the concentration of K+ on the fetal side. These observations suggest that the F-M transfer of Na+ has three components: diffusion through paracellular routes; convective flow by filtration through wide placental pores, and transcellular transport by a mechanism which is uncertain at present.

Animals↗
PubMed1994

Parallel mechanisms of Ca++ transfer across the perfused human placental cotyledon.

OBJECTIVES: We dissected the paracellular and transcellular components of Ca++ transfer across the perfused human placental cotyledon and explored the nature of the transcellular component. STUDY DESIGN: Transfer of 45Ca++ and ethylenediaminetetraacetic acid labeled with chromium 51 was measured across the in vitro perfused cotyledon of the human placenta, and paracellular and transcellular components of the transfer of Ca++ were calculated from the transfer of the two tracers. RESULTS: The transcellular component of the Ca++ transfer in the maternal-fetal direction represented about one third of the total maternal-fetal transfer. It was saturable, sensitive to cyanide, and insensitive to verapamil. The transcellular component in the fetal-maternal direction was not different from zero. The in vitro transfer rates correlated well with the transfer rates estimated for the in vivo situation from data published in the literature. CONCLUSION: There is a significant active transport of Ca++ across the human placenta in the maternal-fetal direction.

Biological Transport, Active↗
PubMed1993

Evidence for active maternal-fetal transport of Na+ across the placenta of the anaesthetized rat.

1. In order to investigate mechanisms of Na+ transfer, the unidirectional maternal-fetal clearance (Kmf) of 22Na+ and of 51Cr-EDTA (a marker of paracellular diffusion) was measured across the intact or umbilically or dually perfused placenta of the anaesthetized rat. 2. The Kmf of 22Na+ in the intact preparation (18.5 +/- 2.7 microliters min-1, mean +/- S.D., n = 105 placentas) exceeded that of 51Cr-EDTA in the same experiments (1.4 +/- 0.3 microliters min-1) by more than ten times, whereas the difference in their diffusion coefficients in water was only 2-fold. In the perfused preparations the difference in the Kmf values was 6-fold. 3. Assuming that a simple model of paracellular diffusion through wide pores was one component of transfer, the Kmf of 51Cr-EDTA and the diffusion coefficients were used to calculate a component of 22Na+ clearance (Kmf,residual) and of Na+ flux (Jmf,residual) across the perfused placentas which could not be accounted for by transfer through the paracellular route. 4. Kmf,residual of 22Na+ across the dually perfused placenta was significantly lower when temperature was reduced, the temperature quotient (Q10) of the transfer being about 2. Kmf,residual was also significantly lower when 0.1 mM ouabain was perfused on the fetal side. Jmf,residual exhibited saturation kinetics characterized by an apparent Michaelis constant (Km) of 90 mM. Kmf,residual was not influenced by 0.5 mM frusemide, 0.5 mM amiloride or by 0.5 mM hydrochlorothiazide administered to the maternal side. It was significantly increased by 1 mM alanine on the maternal side suggesting that the coupled transfer of Na+ and amino acids may contribute significantly to the maternal-fetal flux of Na+. 5. These observations suggest that most (80%) of the maternal-fetal flux of Na+ across the rat placenta is effected by active transcellular transport. This transport involves passive entry of Na+ into the trophoblast from the maternal side by a largely unknown saturable mechanism and active extrusion of Na+ from trophoblast to the fetal side by Na(+)-K(+)-ATPase.

Anesthesia↗
PubMed1993

Mechanisms of potassium transfer across the dually perfused rat placenta.

The purpose of this study was to directly investigate the mechanisms of K+ transfer across the rat placenta, which was isolated and perfused through both its maternal and fetal circulations. Unidirectional maternofetal (Kmf) and fetomaternal (Kfm) clearances for 42K, 51Cr-labeled EDTA (used as a diffusion-limited paracellular marker), and 3H2O (used as a flow-limited marker) were respectively 232 +/- 36, 12 +/- 4, and 1,020 +/- 260 (mf) and 96 +/- 26, 18 +/- 6, and 737 +/- 176 (fm) microliters.min-1 x g placenta-1. Calculated K+ fluxes were asymmetric, being 0.75 +/- 0.12 and 0.41 +/- 0.12 mumol.min-1 x g placenta-1 for maternofetal and fetomaternal, respectively (mean +/- SE, n = 6; P < 0.01, paired t test). Although Kmf for 3H2O was 28% higher than Kfm, this could not completely account for the asymmetry in K+ fluxes. Kmf for 42K was 12-70 times higher than that for 51Cr-EDTA (presumed to be a paracellular marker), although its diffusion coefficient is only 2.5 times higher. An apparent Michaelis constant (Km) of 11.0 +/- 2.4 mM and maximum velocity (Vmax) of 3.8 +/- 0.33 mumol.min-1 x g placenta-1 was calculated by Michaelis-Menten analysis of the transcellular component of maternofetal flux (Jmf) for K+. Ouabain or barium (1 mM in maternal and fetal perfusate) reduced Kmf for 42K from 250 +/- 38 to 76 +/- 13 microliters.min-1 x g placenta-1 (n = 4; P < 0.01) and from 358 +/- 31 to 106 +/- 18 microliters.min-1 x g placenta-1 (n = 5; P < 0.001). Neither drug had any effect on Kmf for 51Cr-EDTA or 3H2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Asymmetrical transfer of inert hydrophilic solutes across rat placenta.

Transfer of [14C]mannitol, 51Cr-labeled EDTA, and [14C]-inulin from mother to fetus and from fetus to mother was measured in rats under pentobarbital anesthesia. The clearance of the three substances from the mother to fetus (Kmf) was 2.69 +/- 0.38, 1.93 +/- 0.73, and 0.47 +/- 0.14 microliter/min (means +/- SE), respectively, and the clearance from fetus to mother (Kfm) was 5.97, 6.66, and 4.95 microliters/min, respectively (the SE could not be estimated). Kfm appears to be consistently higher than Kmf by an almost constant value of approximately 4 microliters/min. To explain this a hypothesis was proposed according to which volume flow circulates across the placenta. Solute-free water is driven transcellularly across the placental barrier from the maternal to the fetal side by a difference of osmotic pressure created by active transport of some solutes (mainly Na+) to the fetus. Water together with all solutes dissolved returns from fetus to mother by filtration through wide extracellular channels in the placenta down a hydrostatic pressure gradient.

Amniotic Fluid↗
PubMed1992

Utility of an oral examination in a surgical clerkship.

To evaluate the utility of the oral examination in a surgical clerkship, we designed a prospective and randomized study to relate the subjective impressions of experienced examiners with an objective measure of cognitive knowledge. The examiners were asked to score the student's performance as honors, high satisfactory, satisfactory, or unsatisfactory, according to their subjective impression of the student's ability. Student performance was grouped according to oral examination performance. The cognitive performance in the honors group was significantly better than that of the other groups (Student's t-test, p = 0.05). There was a significant difference in cognitive performance for oral examination groups throughout the rotations (analysis of variance, p = 0.000; Kruskal Wallis, p = 0.05). The oral examination is useful to identify a high level of cognitive achievement but cannot discriminate between groups of median to low competence. It should be used for educational feedback, career counseling, residency recommendations, and professional development.

Achievement↗
PubMed1990

Transport of calcium across the dually perfused placenta of the rat.

1. A rat placenta was dually perfused in situ with modified Krebs fluid. Perfusion was carried out through the femoral artery on the maternal side and through the umbilical artery on the fetal side. 2. Transfer of 45Ca2+ and [3H]L-glucose across the placenta was measured in the maternal-fetal direction. The transcellular component of the maternal-fetal transport of Ca2+, Jmf,tc, was estimated from transfer rates of the two tracers and from Ca2+ concentration in maternal perfusate, [Ca2+]m. 3. At [Ca2+]m of 1.1 mM (physiological concentration of Ca2+ in plasma) Jmf,tc was 92.4 +/- 13.7 nmol min-1 (mean +/- S.D.), which is about 90% of the transport expected in an intact placenta. The permeability-surface area product (PS) of the placenta to [3H]L-glucose was 13.8 +/- 3.9 microliters min-1, about 4 times higher than that expected in intact placenta. 4. Transport of 45Ca2+ changed rapidly when [Ca2+]m was varied. Kinetic constants of the transcellular transport of Ca2+ are the Michaelis constant, Km, = 0.45 mM and the maximum rate of transport, Vmax, = 116 nmol min-1. It follows from this that at physiological levels of Ca2+, transport of Ca2+ to the fetus is relatively independent of changes in [Ca2+]m. 5. Strontium and barium (SrCl2 and BaCl2, 1 mM) decreased Jmf,tc; the response was prompt and reversible. Magnesium (2 mM) had no effect. Maternal-fetal transport of 85Sr2+ and 133Ba2+ was decreased rapidly and reversibly by elevating [Ca2+]m from 0.35 to 2 mM. These observations suggest that Sr2+ and Ba2+ are transported across the placenta by the Ca2+ transport system. This means that the transport is not substrate specific. 6. Cadmium (1 mM-CdCl2) decreased Jmf,tc irreversibly with some latency. The slowness of the response suggests a non-competitive inhibition. Cadmium (0.02 mM-CdCl2) was without effect on Jmf,tc. 7. A Ca2+ channel blocker, nifedipine (10 microM), administered to the maternal side had no effect on Jmf,tc.

Animals↗
PubMed1988

A prospective, randomized trial of perioperative prophylactic cefamandole in elective colorectal surgery for malignancy.

The impact on wound infection of the addition of perioperative cefamandole to a mechanical bowel preparation with oral antibiotics was studied in a prospective randomized series of patients undergoing elective colectomy for biopsy-proven carcinoma or adenomatous polyps. Seventy patients were randomized, all underwent mechanical bowel preparation and received oral neomycin and erythromycin base. Thirty-four patients also received a preoperative and four postoperative doses of cefamandole, while 36 patients were randomized to receive no parenteral antibiotics. The two groups were well stratified for age, sex, and risk factors. The Dukes stage was similar and the surgical procedures were equally distributed in the two groups. There were no wound infections in the 34 patients receiving cefamandole and only one wound infection (2.8 percent) in the 36 control patients. Therefore, the addition of perioperative intravenous cefamandole to a good mechanical bowel preparation with oral antibiotics was of no benefit in reducing wound infections following resection of colorectal malignancies in this select group of patients.

Carcinoma, Squamous Cell↗
PubMed1988

Adenocarcinoma of the appendix.

Sixteen instances of adenocarcinoma of the appendix treated at Roswell Park Memorial Institute between 1964 and 1986 were reviewed. Thirteen of 15 were mucinous and ten were well differentiated. Synchronous metastases were present in 11 patients, with carcinomatosis being the most common pattern of metastases (nine patients). Seven of eight women had ovarian metastases. Nine of the 11 patients with metastatic disease presented with complaints referrable to the metastatic site. The five year survival rate was 50 per cent in the eight patients who underwent right hemicolectomy and 25 per cent in the four patients who underwent appendectomy. The data from this review support right hemicolectomy as the treatment of choice for adenocarcinoma of the appendix. The prolonged survival time of patients with metastatic disease and the symptomatic nature of that disease support the application of palliative oophorectomy in patients with ovarian metastases.

Adenocarcinoma, Mucinous↗
PubMed1987

A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma.

Seventy-four previously untreated patients with metastatic colorectal adenocarcinoma were prospectively randomized into one of three treatment regimens: (1) 5-fluorouracil (5-FU) 450 mg/m2 as an intravenous (IV) bolus daily for five days or toxicity, then 200 mg/m2 IV bolus every other day for six doses; (2) methotrexate (MTX) 50 mg/m2 in normal saline by IV infusion over four hours followed by an IV bolus of 5-FU 600 mg/m2. This was administered weekly for 4 weeks and then every 2 weeks. (3) Leucovorin 500 mg/m2 in a two-hour IV infusion of normal saline with 5-FU 600 mg/m2 as an IV bolus one hour after the Leucovorin began every week for 6 weeks. The combined complete and partial response rates in the three regimens were 11%, 5%, and 48%, respectively (P = .0009). The median duration of response in the 5-FU and Leucovorin regimen was 10 months. There was no statistically significant difference between the treatment regimens with respect to survival time (P = .6). Toxicity in the 5-FU and Leucovorin regimen was predominantly diarrhea (13 of 30 patients, 40%). In this regimen, eight of 13 patients (52%) who developed diarrhea not only required a dose reduction of 5-FU, but also hospitalization for IV hydration. The predominant toxicity in the 5-FU alone regimen and the 5-FU and MTX regimen was leukopenia. One drug-related death occurred in each regimen.

Adenocarcinoma↗
PubMed1986

Transport of calcium by the placenta of the rat.

Transport of 45Ca and of radioactively labelled inert saccharides across the intact or perfused placenta was measured in the rat on day 21 of pregnancy, the day after mating being day 1. The values of permeability--surface area product (PS) of the intact placenta to radioactive mannitol, sucrose, raffinose, and methoxyinulin were approximately proportional to their diffusion coefficients in water. This suggests that diffusion of inert hydrophilic molecules across the rat placenta takes place through wide aqueous channels. Net flux of Ca from mother to fetus, estimated from the increase of the fetal Ca content between day 20 and day 21 is 100 +/- 4 nmol min-1 (the limits here and below are S.E. of means). The unidirectional maternal-fetal flux of Ca (Jmf) in non-anaesthetized animals, estimated from the flux of 45Ca, is 100 +/- 7 nmol min-1. The similarity of the two values suggests that the fetal-maternal flux (Jfm) is small The umbilical vascular bed of the rat placenta was perfused in situ with Krebs-dextran fluid. Jmf estimated from the transfer of 45Ca from maternal plasma to perfusate was 81 +/- 4 nmol min-1. PS of the perfused placenta to radioactive sucrose was 2.6 +/- 0.3 microliter min-1. Jmf decreased reversibly when the placenta was perfused with 0.5 mM-dinitrophenol or 1 mM-CN-, which is consistent with the presumed active nature of the maternal-fetal transport of Ca. Jmf did not decrease when the placenta was perfused with Na-free fluids (substitution with Tris, Li or sucrose), indicating that Na-Ca exchange across the fetal border of the placental trophoblast is not involved in maternal-fetal transport of Ca. Transport of 45Ca to the perfusate was reduced to about 60% when maternal plasma concentration of Ca was doubled. This suggests that the affinity of the maternal-fetal transport system to Ca is high. Jmf did not change when the umbilical concentration of Ca was varied between 0.1 and 3 mM. There thus seems to be no rapid feed-back between umbilical concentration of Ca and transport of Ca from mother to fetus. Fetal-maternal transfer of Ca, estimated from the steady-state extraction of 45Ca from the umbilical perfusate, is only about 20% of the maternal-fetal transfer. Umbilical extraction of 45Ca changed only little when umbilical concentration of Ca was varied between 0.1 and 3 mM. This suggests that either most of the fetal-maternal transport of Ca is diffusional or the fetal-maternal transport system has a very low affinity to Ca.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia↗