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Biomedical subjects

H Schulman

Publications and source records attributed to H Schulman.

At least 109 records · Page 6Linked to original sources
PubMed1992

Transvaginal ultrasound, color flow, and Doppler waveform of the postmenopausal adnexal mass.

One thousand postmenopausal women were examined prospectively with transvaginal ultrasound. Seven hundred forty-three (74%) were asymptomatic and presented for screening. Data were analyzed to determine the accuracy of this new modality. Eighty-three women had surgery, and 29 malignant neoplasms were found. Color flow was identified in 27 of 29 malignant tumors and 35% of benign masses. A cutoff value of 0.41 for the Doppler resistance index in the feeder vessels had the best discriminatory value; sensitivity and specificity were 96 and 95%, respectively, for separating benign from malignant neoplasms. Positive and negative predictive values were 96 and 95%, respectively. Morphology alone had poor sensitivity, but when combined with Doppler indices, the sensitivity improved to 90% and the positive and negative predictive values were 90 and 96%, respectively. The results of this study suggest that in the postmenopausal ovary, transvaginal B-mode imaging, color flow, and Doppler indices satisfy criteria as tests that may be sensitive and specific enough for application in a screening program.

Adult↗
PubMed1991

Doppler studies of the uteroplacental circulation in pregnancies complicated by diabetes.

The aim of this study was to evaluate the uteroplacental side of the circulation in pregnancies complicated by diabetes. A total of 54 women with pregnancies complicated by diabetes underwent uterine and umbilical artery Doppler studies. Uterine Doppler velocity waveforms were not obtained in two women. The prevalence of abnormal uterine artery velocity waveforms was much higher than in a non-diabetic population (15.4% vs. 2%, p < 0.001). Those eight women with abnormal uterine Doppler studies had a statistically higher incidence of poor glycemic control, chronic hypertension, polyhydramnios, vasculopathy, pre-eclampsia, Cesarean births for fetal distress and newborns with respiratory distress syndrome. In this group of patients, the umbilical circulation was not considered to be a contributing factor in the development of problems.

Journal Article↗
PubMed1991

The pathophysiology of acute syphilitic funisitis.

There is an increase in the number of cases of syphilis in pregnancy in the United States. Fetal death may occur in syphilis from acute or chronic infections. A case is presented in which an acute fetal infection occurred. The patient presented at 31 weeks' gestation, with a decrease in fetal movements and non-reactive cardiotocography. Ultrasound and Doppler analysis of the fetal heart, cerebral and umbilical arteries, aorta and umbilical vein led to the suspicion of acute cardiac failure. An amniocentesis yielded a white cell count of 1122 white blood cells, with 91% polymorphs, but the Gram stain was negative. The fetus developed a persistent bradycardia and was delivered. The diagnosis of acute severe syphilitic funisitis was suspected from histological sections of the cord. Diagnosis was established from maternal and fetal blood. Modern ultrasound techniques, including imaging, Doppler and cardiotocography, can lead to the analysis of the pathophysiology of disease states. An acute syphilitic infection should be suspected when this constellation of findings is found.

Journal Article↗
PubMed1991

Unique phosphorylation site on the cardiac ryanodine receptor regulates calcium channel activity.

Ryanodine receptors have recently been shown to be the Ca2+ release channels of sarcoplasmic reticulum in both cardiac muscle and skeletal muscle. Several regulatory sites are postulated to exist on these receptors, but to date, none have been definitively identified. In the work described here, we localize one of these sites by showing that the cardiac isoform of the ryanodine receptor is a preferred substrate for multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase). Phosphorylation by CaM kinase occurs at a single site encompassing serine 2809. Antibodies generated to this site react only with the cardiac isoform of the ryanodine receptor, and immunoprecipitate only cardiac [3H]ryanodine-binding sites. When cardiac junctional sarcoplasmic reticulum vesicles or partially purified ryanodine receptors are fused with planar bilayers, phosphorylation at this site activates the Ca2+ channel. In tissues expressing the cardiac isoform of the ryanodine receptor, such as heart and brain, phosphorylation of the Ca2+ release channel by CaM kinase may provide a unique mechanism for regulating intracellular Ca2+ release.

Amino Acid Sequence↗
PubMed1991

Activation of chloride channels in normal and cystic fibrosis airway epithelial cells by multifunctional calcium/calmodulin-dependent protein kinase.

Cystic fibrosis is associated with defective regulation of apical membrane chloride channels in airway epithelial cells. These channels in normal cells are activated by cyclic AMP-dependent protein kinase and protein kinase C. In cystic fibrosis these kinases fail to activate otherwise normal Cl- channels. But Cl- flux in cystic fibrosis cells, as in normal cells, can be activated by raising intracellular Ca2+ (refs 5-10). We report here whole-cell patch clamp studies of normal and cystic fibrosis-derived airway epithelial cells showing that Cl- channel activation by Ca2+ is mediated by multifunctional Ca2+/calmodulin-dependent protein kinase. We find that intracellular application of activated kinase and ATP activates a Cl- current similar to that activated by a Ca2+ ionophore, that peptide inhibitors of either the kinase or calmodulin block Ca2(+)-dependent activation of Cl- channels, and that a peptide inhibitor of protein kinase C does not block Ca2(+)-dependent activation. Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1991

Activation of multifunctional Ca2+/calmodulin-dependent protein kinase in GH3 cells.

We report that the rat pituitary cell line GH3 contains a Ca2(+)- and calmodulin-dependent protein kinase with properties characteristic of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) from rat brain. The GH3 kinase exhibits the hallmark of authentic CaM kinase: conversion from Ca2(+)-dependent to Ca2(+)-independent activity following a brief initial phosphorylation in vitro. This phosphorylation occurs at a site which is similar or identical to that of the "autonomy" site of the rat brain enzyme and thus may be an autophosphorylation event. GH3 CaM kinase is phosphorylated and becomes Ca2(+)-independent in situ. Depolarization of intact cells with K+ opens calcium channels and leads to the phosphorylation of CaM kinase at the autonomy site, and the kinase becomes significantly and persistently Ca2(+)-independent. Treatment of cells with thyrotropin-releasing hormone (TRH), which activates the phosphatidylinositol signaling pathway, also generates a Ca2(+)-independent CaM kinase in situ. The primary effect of TRH on CaM kinase activity is transient and correlates with the spike of Ca2+ released from intracellular stores and the rapid phase of prolactin release from GH3 cells. This study demonstrates that CaM kinase is able to detect and respond to both calcium that enters the cell through voltage-sensitive Ca2+ channels and calcium released from internal stores via the phosphatidylinositol pathway. We find that TRH, a hormone that causes release of prolactin and was previously believed to activate primarily protein kinase C, also significantly activates CaM kinase in intact cells.

Animals↗
PubMed1991

Phosphorylation of microtubule-associated protein-2 in GH3 cells. Regulation by cAMP and by calcium.

The rat pituitary cell line GH3 contains a high molecular weight microtubule-associated protein with properties characteristic of microtubule-associated protein-2 (MAP-2). The 280-kDa protein is selectively immunoprecipitated by antibodies to authentic bovine brain MAP-2 and is phosphorylated at appropriate sites by cAMP-dependent protein kinase (cAMP kinase) and multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase). Although MAP-2 is a minor cellular constituent, it can be immunoprecipitated from [32P]Pi-labeled GH3 cells and shown to contain a high level of basal phosphorylation. Vasoactive intestinal peptide, forskolin, 3-isobutyl-1-methylxanthene, or cholera toxin, treatments which increase cellular cAMP levels, or dibutyryl cAMP stimulate phosphorylation of specific sites on MAP-2 without significantly increasing its high state of basal phosphorylation. Phosphopeptide mapping reveals that the sites phosphorylated by cAMP kinase in vitro are the same sites whose phosphorylation in situ increases following stimulation of GH3 with agents that activate cAMP kinase. Increasing intracellular Ca2+ levels in GH3 cells also stimulates phosphorylation of MAP-2 but at sites distinct from those phosphorylated following treatment with cAMP inducing agonists. Phosphopeptide mapping indicates that the sites phosphorylated by CaM kinase in vitro are the same sites whose phosphorylation in situ increases following Ca2(+)-mediated stimulation. We conclude that activation of cAMP- and Ca2(+)-based signaling pathways leads to phosphorylation of MAP-2 in GH3 cells and that cAMP kinase and CaM kinase mediate phosphorylation by these pathways, respectively.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Gastric "pseudolymphoma" with restricted light chain expression in a patient with obscure gastrointestinal blood loss.

We present a case report of a gastric "pseudolymphoma" (GL) that exhibits restricted light chain expression and, therefore, illustrates the dilemma encountered when histologically benign lesions have phenotypic abnormalities suggesting malignancy. For many years this lesion has been considered usually benign; however, recent reports such as this one demonstrate immunologic signs of monoclonality in an otherwise histologically benign lesion. This finding challenges our assumptions as to the nature of this lesion and our definition of cancer. The lesion also displays "Castleman-like" features (angiofollicular hyperplasia) as well as "common inflammatory" germinal centers. In addition we briefly review the literature.

Aged↗
PubMed1991

Primary lymphoma of brain in childhood.

Primary brain lymphoma is exceedingly rare during the first decade of life. We report an unusual case, not only being one of the youngest presented, but also because of the unusual CT features exhibited.

Brain Neoplasms↗
PubMed1991

Regulation of Cl- channels by multifunctional CaM kinase.

cAMP kinase has been shown to mediate the cAMP pathway for regulation of Cl- channels in lymphocytes, but the mediator of an alternative, Ca2+ pathway has not been identified. We show here that Ca2+ ionophore activates Cl- currents in cell-attached and whole-cell patch-clamp recordings of Jurkat T lymphocytes, but this activation is not direct. The effect of Ca2+ ionophore on whole-cell Cl- currents is inhibited by a specific peptide inhibitor of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase). Furthermore, Cl- channels are activated in excised patches by purified CaM kinase in a fashion that mimics the effect of Ca2+ ionophore in cell-attached recordings. These results suggest that CaM kinase mediates the Ca2+ pathway of Cl- channel activation.

Adenosine Triphosphate↗
PubMed1991

Activation of multifunctional Ca2+/calmodulin-dependent kinase in intact hippocampal slices.

In vitro phosphorylation of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) converts it to a form that is independent of Ca2+. We demonstrate that significant Ca(2+)-independent CaM kinase activity is present in untreated hippocampal slices. Two manipulations that produce a long-lasting enhancement of neuronal activity in hippocampal slices, elevated extracellular Ca2+ or depolarization with high K+, generate additional Ca(2+)-independent activity. This increase is dependent on extracellular Ca2+ and is correlated with an increased phosphorylation of CaM kinase. In contrast, CaM kinase in posterior pituitary, a brain structure that is not thought to be involved in memory-related processes, is not modulated by depolarization. These results suggest that the Ca(2+)-independent form of CaM kinase may modulate neuronal activity in the hippocampus.

Animals↗
PubMed1991

Serine/threonine kinases in the nervous system.

Three principal serine/threonine kinases that catalyze protein phosphorylation in response to second messengers are: cAMP-dependent protein kinase, multifunctional Ca2+/calmodulin-dependent protein kinase, and protein kinase C. Studies are now focusing on the distinct isoforms of these kinases that may subserve specific functions in some systems, and on providing a more molecular understanding of kinase functions. Combined genetic and biochemical approaches are beginning to be used to define unique roles for these kinases.

Animals↗
PubMed1991

Transvaginal color flow Doppler in the assessment of ovarian and uterine blood flow in infertile women.

OBJECTIVE: To measure the flow velocity of the uterine and ovarian arteries through the menstrual cycle to determine there are changes. DESIGN: Serial measurements throughout the menstrual cycle in women attending an infertility clinic, compared with volunteers coming for annual examinations. Transvaginal ultrasound-color flow Doppler was the investigative tool. SETTING: A University Hospital ambulatory care center. PATIENTS: One hundred infertile women compared with 150 women attending the clinic for annual checkups. MAIN OUTCOME MEASURES: Changes in the resistance index of flow velocity waveforms of the uterine and ovarian arteries. RESULTS: Uterine flow velocity has a resistance index of 0.88 +/- 0.04 (2 SE) in the proliferative phase and starts to decrease the day before ovulation. A nadir of 0.84 +/- 0.04 is reached on day 18 and remains at that level for the rest of the cycle. In anovulatory cycles, these changes do not occur. A subgroup of 12 women who lacked end diastolic flow in the uterine arteries during the secretory phase were identified. Eleven of these women were infertile, 8 of whom with primary infertility. Ovarian artery flow velocity is usually detected when the dominant follicle reaches 12 to 15 mm. The resistance index is 0.54 +/- 0.04 and also declines on the day before ovulation. A nadir of 0.44 +/- 0.04 is reached 4 to 5 days later and slowly rises to 0.050 +/- 0.04 before menstruation. CONCLUSIONS: There are changes in the flow velocity patterns of the uterine and ovarian arteries during the normal ovulatory menstrual cycle. Because these changes in flow velocity begin before ovulation, it can be suspected that they may involve angiogenesis as well as hormonal factors. The changes noted in these studies are statistically significant but may be too small to be used as a diagnostic tool in the study of infertility problems.

Adult↗
PubMed1991

Ectopic pregnancy: transvaginal color Doppler of trophoblastic flow in questionable adnexa.

The purpose of this study was to see if color flow Doppler measurements could aid in the positive diagnosis of ectopic pregnancy when no gestational sac can be seen in the adnexa. We examined 148 women with abdominal pain and suspected ectopic pregnancy by abdominal ultrasonography, followed by vaginal ultrasonography and color Doppler when the diagnosis was still uncertain. Seventy-three patients proved to have ectopic pregnancies. Color flow with low resistance and high velocity vascular signals were observed in complex adnexal masses and in some of the corpora lutea. The resistance index for ectopic trophoblast was 0.36 +/- 0.02 SD. Color Doppler had both positive and negative discrimination of adnexal masses (P = 10(-15). The resistance index for the corpora lutea was 0.48 +/- 0.04. A cutoff value of 0.40 or less is proposed as a diagnostic index for suspected trophoblast in the adnexa. In nine cases of ectopic pregnancy, no color flow was noted. In these women, the beta-human chorionic gonadotropin level was less than 1000 mIU/ml. The clinical operative suspicion in these cases was tubal abortion. Sensitivity and specificity were 88% and 97%, respectively, in this highly selective series. Positive and negative predictive values were 97% and 89%. Color Doppler appears to be useful for the positive diagnosis of ectopic pregnancy with ultrasonography when no adnexal gestational sac is observed. Prospective randomized trials will determine the ultimate clinical value of these findings.

Adnexa Uteri↗
PubMed1991

Fibrolamellar carcinoma of the liver in pregnancy. A case report.

Fibrolamellar carcinoma of the liver is a rare tumor that has not been previously reported to occur during pregnancy. A 22-year-old, pregnant Arab woman with documented fibrolamellar carcinoma of the liver was followed at our high-risk pregnancy unit. Despite the severity of the disease, the pregnancy and delivery were uneventful.

Adult↗
PubMed1990

Ca2+/calmodulin kinase is activated by the phosphatidylinositol signaling pathway and becomes Ca2(+)-independent in PC12 cells.

Hormonal activation of the phosphatidylinositol (PI) signaling system initiates a biochemical pathway that bifurcates to increase cellular levels of diacylglycerol and of inositol trisphosphate/Ca2+. Both Diacylglycerol and Ca2+ are known to activate protein kinase C, a primary mediator of the PI signaling system. We now find that the two limbs of the PI pathway utilize distinct multifunctional protein kinases to mediate their cellular effects. An important consequence of Ca2+ elevated by the PI signaling system, when PC12 cells are treated with bradykinin, is the activation of multifunctional Ca2+/calmodulin-dependent protein kinase. This activation stimulates autophosphorylation of CaM kinase at its regulatory domain and converts it to an active, Ca2(+)-independent species that may be a basis for potentiation of Ca2+ transients.

Adrenal Gland Neoplasms↗