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Biomedical subjects

L Rabinowitz

Publications and source records attributed to L Rabinowitz.

At least 19 recordsLinked to original sources
PubMed2000

An ikaros-containing chromatin-remodeling complex in adult-type erythroid cells.

We have previously described a SWI/SNF-related protein complex (PYR complex) that is restricted to definitive (adult-type) hematopoietic cells and that specifically binds DNA sequences containing long stretches of pyrimidines. Deletion of an intergenic DNA-binding site for this complex from a human beta-globin locus construct results in delayed human gamma- to beta-globin switching in transgenic mice, suggesting that the PYR complex acts to facilitate the switch. We now show that PYR complex DNA-binding activity also copurifies with subunits of a second type of chromatin-remodeling complex, nucleosome-remodeling deacetylase (NuRD), that has been shown to have both nucleosome-remodeling and histone deacetylase activities. Gel supershift assays using antibodies to the ATPase-helicase subunit of the NuRD complex, Mi-2 (CHD4), confirm that Mi-2 is a component of the PYR complex. In addition, we show that the hematopoietic cell-restricted zinc finger protein Ikaros copurifies with PYR complex DNA-binding activity and that antibodies to Ikaros also supershift the complex. We also show that NuRD and SWI/SNF components coimmunopurify with each other as well as with Ikaros. Competition gel shift experiments using partially purified PYR complex and recombinant Ikaros protein indicate that Ikaros functions as a DNA-binding subunit of the PYR complex. Our results suggest that Ikaros targets two types of chromatin-remodeling factors-activators (SWI/SNF) and repressors (NuRD)-in a single complex (PYR complex) to the beta-globin locus in adult erythroid cells. At the time of the switch from fetal to adult globin production, the PYR complex is assembled and may function to repress gamma-globin gene expression and facilitate gamma- to beta-globin switching.

Adenosine Triphosphatases↗
PubMed1997

Circadian variation in the natriuresis produced by potassium intake in the rat.

To determine if there was an endogenous circadian regulation of the renal natriuretic response to acute potassium loading, unanesthetized rats, either fed or fasted, were given an intragastric infusion of KCl over 100 min at the times of maximum and minimum circadian sodium excretion, i.e. in the early dark and early light phase of a 12 hour dark/light cycle. During KCl infusion plasma potassium concentration as well as sodium and potassium excretion progressively increased. Cumulative sodium excretion was greater in dark than light phase, and was greater in fed than fasted rats. Sodium excretion was greater at any given elevated level of plasma potassium in the dark than light phase. The results suggest that reported variations in the effects of high potassium diets on sodium excretion, blood pressure, or circulatory pathology in hypertension, may in part be explained by variations in the time of oral potassium intake.

Animals↗
PubMed1996

Aldosterone and potassium homeostasis.

The presently accepted regulators of the homeostatic excretion of potassium are the plasma concentrations of aldosterone and potassium. Evidence for a role of aldosterone is reviewed, and it is pointed out that aldosterone is kaliuretic at supraphysiologic levels but has little kaliuretic activity within its normal secretory range. Elevation of plasma potassium above its normal range enhances the kaliuretic action of aldosterone. Elevation of plasma potassium above, but not within, its normal range is strongly kaliuretic. In sheep the kaliuresis induced by intake of a potassium rich meal cannot be explained by changes in aldosterone or plasma potassium. A kaliuretic reflex arising from receptors in the gut, portal vein or liver has been proposed the explain the meal-induced kaliuresis. This putative reflex involves the central nervous system and efferent kaliuretic factors other than aldosterone and plasma potassium. Evidence for the involvement of the central nervous system and undetermined kaliuretic regulatory factors can be found in studies of the physiologic circadian rhythm of renal potassium excretion. This rhythmic excretion does not appear to depend on changes in either aldosterone or plasma potassium.

Aldosterone↗
PubMed1996

Early effects of uninephrectomy on K homeostasis in unanesthetized rats.

Mechanisms underlying the change in K excretion (UKV) during the first 6 days after uninephrectomy (UNX) were examined in unanesthetized rats. Arterial plasma K concentrations (PK) were 0.55 meq/l above control values at 12 and 24 h after UNX but were not significantly different 36-72 h after UNX. To determine if there was an increased sensitivity of the distal K secretory mechanism to increases in PK, an intragastric KCl infusion was given. The delta UKV/delta PK per kidney values were in the following order: 6-day UNX > 2-day UNX > control. In the normal rats, an acute increase of 0.5 meq/l in PK increased UKV by an amount approximating 25% of the increase in UKV observed 12-24 h after UNX. Amiloride, administered 48 h after UNX, increased Na excretion per kidney and decreased UKV per kidney approximately twice as much in UNX as in control groups. Thus an adaptive increase of amiloride-inhibitable K secretion occurred within 2 days of UNX and continued to increase thereafter. This K adaptation may have been induced by transient increases in PK.

Adaptation, Physiological↗
PubMed1995

Kaliuresis in normal subjects following oral potassium citrate intake without increased plasma potassium concentration.

Ingestion of potassium salts typically induces both a kaliuresis and an increase in the systemic plasma potassium concentration. In this study normal healthy adults undergoing water diuresis ingested potassium citrate or sodium citrate (0.5 mmol/kg body weight) or continued without ion ingestion (a time control group). Urine was collected over 20-min intervals and venous blood sampled at midinterval. Intake of potassium citrate led to a significant increase in potassium excretion that began during the first postingestion collection and peaked 60-80 min after intake with a maximal increase in potassium excretion above baseline of 1.60 mumol/min.kg-1. The kaliuresis occurred without changes in plasma potassium concentration, excretion of creatinine or calcium, or urine hypo-osmolality and was associated with a briefer, smaller, and less regular increase in sodium excretion and a pronounced but irregular increase in chloride excretion. Plasma aldosterone was insignificantly elevated above baseline, and the initial increase did not occur until 40-60 min after potassium intake. Intake of sodium citrate did not produce a kaliuresis. The cause of the kaliuresis does not appear to be an increased systemic plasma potassium concentration, an increased plasma level of aldosterone, intake of citrate, or an elevated excretion of sodium. The mechanism inducing the kaliuresis following oral potassium intake in the absence of changes in systemic plasma potassium may involve a reflex initiated at potassium sensors in gut, portal vein, or liver.

Administration, Oral↗
PubMed1994

Circadian rhythms and time course of adaptive sodium and potassium excretion in rats after uninephrectomy.

The relationship between renal circadian cyclic excretion and renal compensatory adaptation after uninephrectomy for K, Na, and water was studied. Rats in a 12:12-h light-dark environment were given a liquid diet, and urine was collected for 16 days with consecutive 90-min periods. Days 1-4 were control, 5-10 followed a sham operation, and 11-16 followed uninephrectomy. The major findings were 1) the circadian cycles in excretion were virtually unchanged after sham and uninephrectomy; 2) an adaptive increase in excretion of Na, K, and water by the remaining kidney occurred within 90 min after uninephrectomy; 3) after uninephrectomy the distribution of the 24-h increment in excretion for the remaining kidney closely followed the preexisting pattern of circadian excretion for Na but was evenly distributed between light and dark phases for K; and 4) after uninephrectomy the ratio of excretion to intake was unchanged. This is the first study to document the time course of adaptation to uninephrectomy using consecutive brief collections over several days in unanesthetized and undisturbed rats. Adaptation after uninephrectomy occurred essentially immediately; was maintained unchanged; and preserved Na, K, and water homeostasis. Uninephrectomy did not alter the circadian control of excretion.

Animals↗
PubMed1993

The central nervous system in potassium homeostasis.

There is considerable evidence that the central nervous system (CNS) is significantly involved in potassium homeostasis: (a) Potassium-specific receptors located in the liver or hepatic portal circulation initiate a reflex increase in potassium excretion via vagal afferents. This reflex is lost or diminished with hypophysectomy. (b) Oscillators, presumably located in the hypothalamus, determine a circadian rhythm in the renal excretion of potassium. The efferent control factors are unknown. (c) Exogenous hypophysial peptides (vasopressin, oxytocin, and alpha-, beta-, and gamma-MSH) stimulate increased potassium (and sodium) excretion. (d) Hypophysial gamma-MSH or a related hypophysial peptide stimulates an increase in the excretion of potassium (and sodium) following uninephrectomy in the rat. This adaptive response involves cerebral, naloxone-inhibitable opioid receptors. (e) Intra-third-ventricular infusion of hypertonic NaCl initiates an increased potassium (and sodium) excretion through undetermined humoral mechanisms and is blocked by prior hypophysectomy. (f) In rats depleted of potassium by low potassium intake or by production of DOCA hypertension, an inhibition of skeletal muscle Na+, K(+)-ATPase ion pump activity is directed by hypothalamic centers and involves inhibition by alpha-adrenergic activity of slow twitch fibers and inhibition by undetermined humoral factors of fast twitch fibers. (g) Potassium receptors, either demonstrated or inferred, initiate reflex increases in respiration, heart rate, blood pressure, and peripheral tissue potassium uptake as well as a reflex inhibition of skeletal muscle ion pumps. (h) Evidence for CNS regulation of potassium intake is equivocal. Major gaps exist in this emerging picture of neuroendocrine involvement in potassium homeostasis.

Animals↗
PubMed1989

Hemodynamic changes after nafcillin administration during coronary artery bypass surgery.

The hemodynamic response to nafcillin administration was studied in 45 patients with good left ventricular function and no known history of hypersensitivity to penicillin during coronary artery bypass grafting (CABG). Group I (15 patients) received 1 gram of nafcillin in 10 mL of saline as an intravenous (IV) bolus, group II (15 patients) received 1 gram of nafcillin in 50 mL of saline as a slow IV infusion over 15 minutes, and group III (15 patients) did not receive nafcillin. Hemodynamic variables and plasma histamine and catecholamine levels were measured before and after nafcillin administration, after 500 mg of CaCl2, and after 0.1 mg of phenylephrine. Bolus nafcillin administration produced profound hypotension secondary to vasodilatation with significant increases in cardiac index and decreases in systemic and pulmonary vascular resistances. Cardiac index increased from 3.15 +/- 0.3 L/min/m2 to 5.75 +/- 0.25 L/min/m2 (P less than 0.005) one minute after nafcillin administration, and remained at 5.1 +/- 0.35 L/min/m2 after administration of CaCl2 (P less than 0.005). All hemodynamic parameters returned toward control values after administration of 0.1 mg of phenylephrine, IV. Plasma epinephrine, norepinephrine, and histamine levels increased more than 100%. In group II, cardiac index increased, while systemic and pulmonary vascular resistances and mean arterial pressure decreased. However, these changes were less significant than those found in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1989

Homeostatic regulation of potassium excretion.

Multiple systems participate in the homeostatic regulation of potassium excretion. Changes in plasma potassium, above a baseline value, will directly stimulate potassium excretion. Acute variations in aldosterone may have only small and perhaps insignificant effects in stimulating potassium excretion when aldosterone is present within its normal plasma range, but may be highly significant in determining the kaliuretic response to changes in plasma potassium or tubular flow rate. Elevation of plasma aldosterone to supraphysiological levels appears to produce increases in potassium excretion. Chronic variations in aldosterone are important, but not unique in determining renal potassium adaptation to chronic variations in potassium uptake. New lines of evidence point to sensors of potassium intake located in the hepatic portal vein or liver, or in enteric locations. A reflex control of potassium excretion, first demonstrated by Aizman and Finkenshtein et al. [120-123] in the dog, and independently suggested in a more general form for the sheep, may be integral in the regulation of potassium excretion in response to intake. With this feedforward control system, potassium excretion may be regulated without changes in systemic plasma potassium concentration. From diverse lines of investigation we find that there is a compelling argument for an important role for the brain in regulating both potassium excretion and its ICF/ECF ratio. One may speculate, albeit on the basis of preliminary information, that separate but analogous systems exist for sodium and for potassium, each involving the brain and each acting through specific humoral factors. For sodium, evidence is accumulating for a ouabain-like humoral agent, perhaps originating in the brain, which modulates renal sodium excretion and the sodium concentration of ICF. Both of these actions have been proposed to have an important influence on blood pressure regulation. The evidence presented here is compatible with a similar system for potassium. On the basis of these studies reviewed here, it is intriguing to speculate that an analogous humoral factor is involved in the regulation of potassium homoeostasis, and that its effects, when understood, may help to resolve current debates regarding the role of potassium in blood pressure regulation.

Aldosterone↗
PubMed1989

Amiloride effect on diurnal cyclic Na and K excretion in rats.

Amiloride was administered to rats during the peak and minimum of Na and K diurnal rhythmic excretion (i.e., during early dark phase and early light phase). In rats receiving a normal-K diet (2.34 meq/day) amiloride decreased K excretion from 186 to 37 mueq/h (dark phase) and from 31 to 4 mueq/h (light phase). Amiloride increased Na excretion from 91 to 344 mueq/h (dark phase) and from 35 to 164 mueq/h (light phase). Rats receiving a high-K diet (10.4 meq/day) showed a higher diurnal peak and minimum for K excretion. During high-K intake, amiloride decreased K excretion from 787 to 191 mueq/h (dark phase) and from 197 to 40 mueq/h (light phase) and increased Na excretion from 237 to 891 mueq/h (dark phase) and from 31 to 222 mueq/h (light phase). Whenever given, amiloride reduced K excretion to approximately 20% of control excretion. It is concluded that rhythmic changes in amiloride-sensitive distal transport are largely, but not entirely, responsible for the diurnal K cycle, but do not cause the concurrent Na cycle. Thus the diurnal cycles in Na and K are expressed through changes in different transport mechanisms. In rats maintained on a high-K diet there is an increase in rhythmic K secretion and Na reabsorption by amiloride-sensitive transport. To maintain Na excretion unchanged, Na reabsorption must be correspondingly depressed at an amiloride-insensitive site.

Amiloride↗
PubMed1988

Aldosterone reverses potassium-induced food aversions in adrenalectomized rats.

Young adult male rats were individually housed and given a standard ration (66 ml) of a liquid diet (Nutrament) each day. The animals were divided into 7 groups: five groups were bilaterally adrenalectomized (ADX) and given one of 5 doses of aldosterone and/or dexamethasone by continuous, osmotic minipump infusions. The remaining two groups served as intact and sham operated controls. Each of the seven groups were subdivided into 3 dietary groups: a basal potassium dietary group, a moderately potassium-supplemented dietary group, and a highly potassium-supplemented dietary group. All rats with intact adrenals as well as those ADX rats given basal or 10 X basal aldosterone treatment consumed all of their allotted 66 ml of diet each day, independent of the level of potassium supplementation. ADX rats given little or no aldosterone treatment that were given access to the moderately or highly supplemented diets became anorexic, eating little or none of the diet. These data are discussed with reference to the factors controlling the intake of ADX rats.

Adrenal Glands↗
PubMed1988

Survival time, causes of death, and tumor/treatment-related morbidity in 100 women with ovarian cancer.

One hundred cases of ovarian cancer were studied at autopsy to determine the effect of morphologic and clinical factors on survival time, the primary cause of death, and tumor/treatment-related morbidity. The mean survival time was 19 months (0 to 174 months). Increasing neoplastic histologic grade and increasing clinical stage at diagnosis were each associated with decreased survival time. In grade I tumors, the mean survival time was 84 months; in grade II tumors, it was 18 months; and in grade III tumors, it was 12 months (P = .0008). Patients who presented in stage I or II had a better survival time (28 months) than those who presented in stage III or IV (15 months) (P = .02). The most common causes of death were disseminated carcinomatosis (48%), infection (17%), pulmonary embolus (8%), and combinations of infection and carcinomatosis (11%). In patients dying of infection, 43% had sepsis, 21% had pneumonia, and 25% had a combination of sepsis and pneumonia. Escherichia coli and Klebsiella were the most common pathogens identified postmortem. Intestinal obstruction (51%) and ureteral obstruction (28%) were the most common forms of tumor-induced morbidity. Bone marrow depression and resultant pancytopenia was the most common form of treatment-induced morbidity.

Adolescent↗
PubMed1988

Distribution of disease at autopsy in 100 women with ovarian cancer.

Clinical and morphologic factors that affected the distribution of disease are described in 100 cases of ovarian cancer at autopsy. In addition to the expected pattern of pelvic and abdominal peritoneal spread, extensive visceral parenchymal metastases were seen: liver parenchyma (45%), lung parenchyma (39%), small and large intestinal wall (52% and 55%), lymph nodes (70%), pancreas (21%), ureter (24%), bone (11%), and brain (6%). Liver parenchymal metastases replaced more than one third of the liver in 25% of cases, whereas lung metastases always involved less than one third of the lungs. When intestinal wall invasion was seen, bowel obstruction was present more often (71%) than when only intestinal serosa was involved (30%). Lymphatic invasion was predictive of lymph node, small intestinal wall, pancreatic, and liver as well as lung parenchymal metastases. Blood vessel invasion was predictive of pancreatic and ureteral metastases. Clinical stage I at diagnosis was associated with high incidences of liver parenchymal (56%), lymph node (56%), lung parenchymal (44%), large intestinal wall (33%), and bone (33%) metastases. Thus, ovarian cancer has parenchymal metastases similar to other carcinomas in addition to its peritoneal spread. Lymphatic and blood vessel invasion is predictive of such involvement. Intestinal wall invasion predicts bowel obstruction.

Adolescent↗
PubMed1988

Homeostatic potassium excretion in fed and fasted sheep.

In unanesthetized adult sheep, following intake of a daily meal, there was a peak in K excretion. The maximum and minimum rates of K excretion following meals were directly related to meal K content. On days without meals, no peak in K excretion occurred. Changes in K excretion on fed and fast days occurred without changes in the low levels of plasma aldosterone and were poorly correlated with urine or blood pH, urine flow rate, Na excretion, or the filtered load of K, but they correlated well with fractional K excretion. Plasma K did not change on fast days. Plasma K increased on some, but not all, fed days. Increases in plasma K that occurred on fed days were insufficient to account for the concurrent kaliuresis. Infusion of aldosterone or isotonic NaCl failed to alter K excretion in fed or fasted sheep. Infusion of isotonic NaCl + aldosterone hypertonic Na2SO4 + aldosterone increased K excretion in fasted but not fed sheep. Infusion of K in the rumen of fed and fasted sheep elevated rumen K concentration and led to increases in K excretion that could not be explained by increases in plasma K. The mechanisms responsible for the homeostatic changes in K excretion on fed and fast days were not ascertained but may importantly depend on sensors of enteric K content.

Aldosterone↗
PubMed1988

Model of homeostatic regulation of potassium excretion in sheep.

Based on experimental observations on unanesthetized sheep, a hypothesis is proposed for the homeostatic control of potassium excretion in this ruminant. This hypothesis includes as a novel element a splanchnic sensor of potassium intake. Information provided by the splanchnic sensor contributes to the control of potassium excretion independently of the level of systemic plasma potassium or other conventional control factors. A mathematical model based on this hypothesis successfully simulates the relations between potassium excretion, plasma potassium, and oral and intravenous potassium input observed in sheep.

Animals↗
PubMed1987

Prediction of intra-uterine growth retardation using maternal glucose tolerance and anthropometric data.

Maternal anthropometric data and the intravenous glucose tolerance test (IVGTT) were investigated as predictors of idiopathic intra-uterine growth retardation (IUGR). Eighty-three eligible subjects without known risk factors for IUGR were enrolled at 30.5 +/- 3.8 weeks' gestation and followed up until delivery at 39.3 +/- 1.9 weeks, at which stage the infants were assessed. There were no differences between the IVGTT profiles of mothers of infants which were appropriate for gestational age and those which were small for gestational age (SGA), irrespective of lenient or strict definitions of SGA. Third-trimester weight gain (grams per week) correlated well with both duration of pregnancy and birth weight (P less than 0.01). Correlations were also found between maternal weight and birth weight, between maternal height/weight ratio and birth weight, and between birth weight and maternal subscapular skinfold thickness.

Adult↗
PubMed1987

Plasma potassium and diurnal cyclic potassium excretion in the rat.

The relation of the plasma potassium concentration to the daily cyclic variation in potassium excretion was examined in undisturbed, unanesthetized male Sprague-Dawley rats maintained on a liquid diet in a 12-h light-dark environment. Potassium excretion increased from a light-phase minimum of 16 mu eq/h to a peak of 256 mu eq/h 3 h after the beginning of the dark phase. Plasma potassium concentration in arterial blood, sampled in rats at 90-min intervals during these changes in potassium excretion, showed no significant change and was in the range 4.50-4.99 meq/liter. In adrenalectomized rats receiving aldosterone and dexamethasone at constant basal rates by implanted pumps, the daily cycle of potassium excretion was the same as in the intact rats, and plasma potassium was not significantly different when measured at the time of minimum and maximum rates of potassium excretion (4.79 +/- 0.42 vs 5.16 +/- 0.47 meq/liter, mean +/- SD). These results indicate that plasma potassium concentration is not the efferent factor controlling diurnal cyclic changes in potassium excretion in adrenal intact rats and may not be the only significant factor in adrenalectomized-steroid replaced rats.

Adrenalectomy↗