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Biomedical subjects

H Schulman

Publications and source records attributed to H Schulman.

At least 163 records · Page 9Linked to original sources

Development of uterine artery compliance in pregnancy as detected by Doppler ultrasound.

Uterine artery velocimetry was performed by means of a continuous-wave Doppler ultrasound. Serial studies were done on 12 nonpregnant and 79 normal pregnant women. Measurements were made on both uterine arteries and averaged. From the proliferative phase of the menstrual cycle through 40 weeks of pregnancy, four developmental phases are described. These changes are based on the calculation of the systolic-diastolic ratio and the disappearance of the early diastolic notch in the velocity wave. The ratio after 26 weeks averaged 2 +/- 0.3. These data provide a foundation for the study of pregnancies in which these normal evolutionary changes do not occur.

Compliance↗

Uterine artery Doppler velocimetry in pregnant women with hypertension.

Uterine and umbilical artery velocimetry was carried out on 71 women with hypertensive disorders in pregnancy. Three categories of hypertensive disease were diagnosed: chronic hypertension, preeclampsia, and chronic hypertension with superimposed preeclampsia. Clinical classifications describe the severity of disease effectively, primarily because the classification is based on the appearance of abnormal physical or laboratory findings. Doppler velocimetry of the uterine arteries shows that normal pregnancy occurs when the systolic/diastolic ratio is less than or equal to 2.6. When the ratio exceeds this level and there is a notch in the waveform, the pregnancy is complicated by stillbirth, premature birth, intrauterine growth retardation, and maternal preeclampsia. The positive and negative predictive value of the examination is 93% and 91%, respectively. It appears that this new technology will be an essential ingredient of optimum pregnancy surveillance.

Adult↗

Activation of the multifunctional Ca2+/calmodulin-dependent protein kinase by autophosphorylation: ATP modulates production of an autonomous enzyme.

The multifunctional Ca2+/calmodulin-dependent protein kinase purified from rat brain cytosol undergoes an intramolecular self-phosphorylation or autophosphorylation. Autophosphorylation produces two strikingly different effects on kinase activity that are dependent on the level of ATP used in the reaction. At low but saturating levels of ATP (5 microM), autophosphorylation causes a 75% reduction in kinase activity, with the residual activity still retaining a dependence on Ca2+ and calmodulin. By contrast, at high but physiological levels of ATP (500 microM), the kinase is converted by autophosphorylation to a form that is autonomous of Ca2+ and calmodulin, with no accompanying reduction in activity. The extent of phosphate incorporation does not determine whether the kinase becomes inhibited or autonomous. Autophosphorylated kinase shows the functional change characteristic of the ATP concentration used during the reaction--inhibited at low ATP and autonomous at high ATP--even when compared at the same level of incorporated phosphate. ATP appears to regulate the site(s) phosphorylated during activation of the kinase and thereby modulates the dual effects of autophosphorylation. Events triggered by transient elevations of cellular Ca2+ may be potentiated and retained by generation of the Ca2+/calmodulin-independent protein kinase activity.

Adenosine Triphosphate↗

Fetal heart rate characteristics that provide confidence in the diagnosis of fetal well-being.

Fetal heart rate monitoring was first used as a clinical tool for the assessment of fetal danger and well-being. In the past decade, basic research has demonstrated the physiologic events associated with most heart rate changes. This review has demonstrated that study and semiquantification of the five analyzable features of an FHR recording can provide a strong reassurance of fetal health. The method has not proven as predictable for defining fetal disease, so additional parameters are needed to define clearly the significance of an abnormal FHR tracing.

Apgar Score↗

Beta 2-adrenergic receptors on peripheral nerves.

We report that peripheral nerves have a functional adenylate cyclase-coupled beta-adrenergic receptor. The pharmacological specificity of this receptor is shown to be of the beta 2 subtype. Two peripheral nerves, the sciatic from the frog and rat and the vagus from the rat, responded to beta 2-agonists with 10-50-fold increases in intracellular cyclic AMP level. This increase was inhibited by the beta-adrenergic antagonist propranolol. In contrast, a central nerve tract, the corpus callosum, responded to isoproterenol with only a minimal one- to twofold increase in cyclic AMP level. These studies demonstrate that peripheral nerves have beta 2-adrenergic receptors that are responsive to exogenously applied catecholamines and suggest a role for these ligands in the previously described modulation of axonal conduction.

Animals↗

Impact of beta-subunit human chorionic gonadotropin and ultrasonography in the management of suspected ectopic pregnancy.

The records of 346 women admitted to the Bronx Municipal Hospital Center with a diagnosis of suspected ectopic pregnancy between 1980 and 1982, when beta-subunit human chorionic gonadotropin and ultrasonography became generally available, were reviewed. The impact of these diagnostic tests on the gynecologic care this population received was to reduce the number of emergency room visits. That often meant a delay in diagnosis. There was no change in hospital stay or characteristics of the patient population. These data suggest that in this type of hospital, culdocentesis should not be abandoned in favor of this new technology.

Adult↗

Umbilical blood flow velocity waveforms in different maternal positions and with epidural analgesia.

Umbilical blood flow velocity waves were measured in the fetuses of healthy parturients in early active labor to assess the influence of different maternal positions (N = 16) and of epidural analgesia (N = 16). The ratio of systolic peak to diastolic trough (S/D) of the umbilical blood flow velocity wave is reflective of vascular resistance distal to the point of measurement on the fetal side of the placenta. Umbilical blood flow velocity wave S/D ratios were significantly higher in the supine than in either lateral position indicating that umbilical artery vascular resistance is increased when the mother lies supine. After epidural blockade, the S/D ratios were unchanged in three and lowered to varying degrees in 13 parturients indicating that this method of pain relief beneficially affects umbilical artery vascular resistance.

Anesthesia, Epidural↗

Umbilical artery velocimetry in diabetes and pregnancy.

Doppler studies of umbilical artery velocity waveforms were performed during the third trimester of pregnancy in 43 diabetic women (18 class A and 25 insulin dependent). A mean serum glucose value of 120 mg% or more was selected to indicate poor glucose control. Systolic to diastolic ratios of umbilical artery velocity waveforms were calculated to determine the degree of placental vascular resistance. A systolic to diastolic ratio of 3 or more was selected as the cut-off value for determining placental vascular disease. A significant positive correlation between systolic to diastolic ratios and serum glucose level (r = 0.52, P less than .001) was found. Elevated systolic to diastolic ratio was associated with increased number of stillbirths and neonatal morbidity. This study suggests that the risk of adverse outcome in diabetic pregnant women correlates with umbilical artery velocity waveforms.

Blood Glucose↗

Surveillance of twin pregnancy with umbilical arterial velocimetry.

A continuous-wave Doppler system and a spectrum analyzer provide the tools for the measurement of systolic-diastolic velocity wave ratios in the umbilical arteries. In twins, each umbilical cord can be studied without imaging the fetuses. Results were tabulated by taking the average difference in the ratios between each fetus and plotting these values against the neonatal weight differences. In 43 twin pregnancies, the data revealed that ratio differences between fetuses that averaged 0.4 or more was predictive of a weight difference of greater than 349 gm. The sensitivity was 73% and specificity 82%. Two cases of twin transfusion syndrome were recognized by the simultaneous presence of high- and low-resistance values.

Adult↗

Ca2+/calmodulin-dependent microtubule-associated protein 2 kinase: broad substrate specificity and multifunctional potential in diverse tissues.

In previous studies, we described a soluble Ca2+/calmodulin-dependent protein kinase which is the major Ca2+/calmodulin-dependent microtubule-associated protein 2 (MAP-2) kinase in rat brain [Schulman, H. (1984) J. Cell Biol. 99, 11-19; Kuret, J. A., & Schulman, H. (1984) Biochemistry 23, 5495-5504]. We now demonstrate that this protein kinase has broad substrate specificity. Consistent with a multifunctional role in cellular physiology, we show that in vitro the enzyme can phosphorylate numerous substrates of both neuronal and nonneuronal origin including vimentin, ribosomal protein S6, synapsin I, glycogen synthase, and myosin light chains. We have used MAP-2 to purify the enzyme from rat lung and show that the brain and lung kinases have nearly indistinguishable physical and biochemical properties. A Ca2+/calmodulin-dependent protein kinase was also detected in rat heart, rat spleen, and in the ring ganglia of the marine mollusk Aplysia californica. Partially purified MAP-2 kinase from each of these three sources displayed endogenous phosphorylation of a 54 000-dalton protein. Phosphopeptide analysis reveals a striking homology between this phosphoprotein and the 53 000-dalton autophosphorylated subunit of the major rat brain Ca2+/calmodulin-dependent protein kinase. The enzymes phosphorylated MAP-2, synapsin I, and vimentin at peptides that are identical with those phosphorylated by the rat brain kinase. This enzyme may be a multifunctional Ca2+/calmodulin-dependent protein kinase with a widespread distribution in nature which mediates some of the effects of Ca2+ on microtubules, intermediate filaments, and other cellular constituents in brain and other tissues.

Animals↗

Mechanism of autophosphorylation of the multifunctional Ca2+/calmodulin-dependent protein kinase.

The multifunctional Ca2+/calmodulin-dependent protein kinase purified from rat brain cytosol undergoes a self-phosphorylation or autophosphorylation reaction. Our conclusion that this reaction is autocatalytic is based on the following lines of evidence: The autophosphorylation reaction and the protein kinase activity toward other substrates are absolutely dependent on the presence of both Ca2+ and calmodulin; autophosphorylation and phosvitin kinase activity show a similar time course and indistinguishable heat lability; the reaction is a consistent property of every preparation of rat brain kinase; the reaction is present in both crude and highly purified preparations of similar kinases or isozymes from rat lung, spleen, heart, bovine brain, and a neuronal tissue from Aplysia californica, a marine mollusk; phosphorylation of the kinase subunits is not mimicked by addition of cAMP, cGMP, Ca2+ plus diglyceride, or addition of the cAMP-dependent protein kinase, and is not blocked by the heat-stable inhibitor protein of the cAMP-dependent protein kinase; and the reaction is intramolecular. Autophosphorylation results in the stoichiometric incorporation of phosphate into both the 51,000- and 60,000-dalton subunits.

Animals↗

Umbilical artery velocity waveforms and intrauterine growth retardation.

A continuous-wave Doppler unit was used to obtain umbilical artery velocity waveforms and to calculate the peak-systolic/diastolic ratio, a reflection of vascular resistance distal to the point of measurement. A total of 587 examinations were performed on 189 women between 18 to 42 weeks' gestation. The neonates were divided in four groups based on their centile birth weight: less than 25%, 25% to 50%, 51% to 75%, and greater than 75% for that gestational age. In all four groups the placental vascular resistance as reflected by the systolic/diastolic ratio fell progressively from the 24 weeks onward. In the lower weight group, placental vascular resistance between 31 to 39 weeks' gestation was higher than in the other three groups (p less than 0.05). For measurements taken between 31 and 39 weeks' gestation we calculated the predictive value of this test in identifying the small-for-gestational age fetus. A ratio of greater than or equal to 3 was defined as abnormal. For the entire population tested, sensitivity was 78% and the specificity was 83%. The predictive value of a positive test was 49%, but when hypertension was present, it was 66%. These findings may prove useful in identifying and managing pregnancies at risk for intrauterine growth retardation.

Blood Flow Velocity↗

Microtubule-associated proteins (MAPs): a monoclonal antibody to MAP 1 decorates microtubules in vitro but stains stress fibers and not microtubules in vivo.

A monoclonal antibody (mAb 7-1.1) was produced against a bovine brain microtubule-associated protein (MAP) preparation that had been separated from tubulin after initial purification by cycles of microtubule assembly and disassembly in vitro. The antibody reacted specifically with two high molecular weight polypeptides of the MAP 1 class, designated MAP 1.1 and MAP 1.2, and also with the surfaces of MAP 1-containing microtubules that had been assembled in vitro. Double immunofluorescence microscopy using mAb 7-1.1 and a well-characterized rabbit anti-tubulin antibody revealed that mAb 7-1.1 stained stress fibers in fixed and permeabilized cultured mammalian cells rather than microtubules. The antibody also stained cell nuclei in a punctate fashion. mAb 7-1.1 is one of a number of monoclonal antibodies that react with presumptive MAP 1 polypeptides. Some of the MAP 1 antibodies have been found to bind specifically to microtubules in fixed and permeabilized cells, while others have been reported to react with nonmicrotubule structures. Our results, together with the results of other investigations, indicate that "MAP 1" may be a family of several high molecular weight polypeptides that adventitiously behave as MAPs by the criterion of in vitro coassembly with tubulin through cycles of polymerization and depolymerization but whose cellular distributions, and perhaps functions, are varied.

Animals↗

Ca2+-dependent phosphorylation of tyrosine hydroxylase in PC12 cells.

Ca2+-dependent protein phosphorylation has been detected in numerous tissues and may mediate some of the effects of hormones and other extracellular stimuli on cell function. In this paper we demonstrate that a Ca2+/calmodulin-dependent protein kinase similar to the enzyme previously purified and characterized from rat brain is present in PC12, a rat pheochromocytoma cell line. We show that Ca2+ influx elicited by various forms of cell stimulation leads to increased 32P incorporation into tyrosine hydroxylase (TH), a major phosphoprotein in these cells. Several other unidentified proteins are either phosphorylated or dephosphorylated as a result of Ca2+ influx. Acetylcholine stimulates TH phosphorylation by activation of nicotinic receptors. K+-induced depolarization stimulates TH phosphorylation in a Ca2+-dependent manner, presumably by opening voltage-dependent Ca2+ channels. Ca2+ influx that results from the direct effects of the ionophore A23187 also leads to TH phosphorylation. Phosphorylation of TH is accompanied by an activation of the enzyme. These Ca2+-dependent effects are independent of cyclic AMP and thus implicate a Ca2+-dependent protein kinase as a mediator of both hormonal and electrical stimulation of PC12 cells.

Animals↗