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Biomedical subjects

R Solomon

Publications and source records attributed to R Solomon.

At least 55 records · Page 3Linked to original sources

Characterization of the prenylated protein methyltransferase in human endometrial carcinoma.

The processing of ras and of other GTP-binding proteins includes a final reversible step in which the carboxy terminal prenylated cysteine is methylated by the enzyme prenylated protein methyltransferase (PPMTase). The significance of this modification and of the role of PPMTase in human tumors has yet to be fully elucidated. Here we characterize the PPMTase of human endometrial carcinomas (tumors in which the frequency of ras gene mutations is relatively high) and compare it to the PPMTase of the normal endometrium. Our results show that in both types of tissues the enzyme is bound to the membranes. It can utilize synthetic substrates such as N-acetyl-S-farnesyl-L-cysteine (Km = 18-20 microM) and is blocked by the PPMTase inhibitor S-farnesylthioacetic acid (Ki = 2 microM). In vitro methylation assays and [alpha-32P]GTP blot-overlay assays showed that the major endogenous PPMTase substrates are small GTP-binding proteins. Methylation of these proteins in vitro is blocked by farnesylthioacetic acid. The kinetic properties of PPMTase from the carcinomas and the normal tissues are very similar. However, levels of PPMTase activity (but not of its endogenous substrates) are higher in the carcinomatous endometrium than in the normal one. The elevated enzyme activity is restricted to the crude mitochondrial fraction (8.0 +/- 0.4 vs. 5.4 +/- 0.1 pmol N-acetyl farnesylcysteine methyl ester formed/min/mg protein by the carcinoma and by the normal endometrial preparations, respectively). As this fraction is enriched in plasma membranes, it appears that the elevated enzyme activity could be related to ras protein methylation; if so, selective methylation blockers might inhibit the growth of endometrial carcinomas.

Endometrial Neoplasms↗

Effect on outcome of the presence or absence of chest pain at initiation of recombinant tissue plasminogen activator therapy in acute myocardial infarction. The Thrombolysis in Myocardial Infarction Investigators.

To ascertain whether the outcome of patients with suspected myocardial infarction differs when chest pain is still present at initiation of thrombolytic therapy, participants in the Thrombolysis in Myocardial Infarction Phase II study, all of whom presented within 4 hours of symptoms onset, were retrospectively divided into 2 groups: (1) those with chest pain present at onset of intravenous thrombolysis, n = 3,000; and (2) those who were free of chest pain on beginning intravenous thrombolytic therapy, n = 337. Patients free of chest pain were older (58 vs 57 years, p = 0.01), more often women (23 vs 17%, p = 0.01), had fewer electrocardiographic leads with ST elevation (3.8 vs 4.1, p < 0.001), and the presenting event was confirmed less often as myocardial infarction than as chest pain without infarction (88 vs 96%, p < 0.001). There were no significant differences between the 2 groups for in-hospital death, reinfarction, recurrent ischemic events, stroke, overall hemorrhagic complications, coronary angioplasty or bypass surgery. At 6-weeks follow-up, more pain-free patients had resting ejection fraction > 0.55 (35 vs 31%, p = 0.001) and fewer developed congestive heart failure (12 vs 20%). At 1-year follow-up, fewer pain-free patients developed congestive heart failure (15 vs 21%, p = 0.009), but no differences existed between the 2 groups in frequency of death, reinfarction, coronary angioplasty, bypass surgery or anginal class. Thus, there are several observations in patients who were free of chest pain at onset of lytic therapy. (1) The majority developed enzymatic or electrocardiographic evidence of acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Electromyographic analysis of standing posture and demi-plié in ballet and modern dancers.

Surface electromyography was used to analyze lower extremity muscle activity during standing posture and demi-plié in first position with lower extremities turned out, in five ballet and seven modern female professional dancers. In standing posture, increased electromyographic (EMG) activity above baseline was detected most frequently at the medial gastrocnemius (54% standing repetitions) and tibialis anterior (29%) electrodes (all dancers); in ballet dancers, increased EMG activity during standing was significantly less frequent at the medial gastrocnemius, but more frequent at the tibialis anterior, than in modern dancers. In demi-plié, the tibialis anterior had a discrete peak of EMG activity at midcycle in all dancers (97% demi-pliés). All dancers also had midcycle EMG activity in both vastus lateralis and medialis (100% demi-pliés). At the end of rising phase of demi-plié, ballet dancers had greater EMG activity than at midcycle in vastus lateralis (100% demi-pliés) and medialis (92%); in modern dancers, end-rising phase voltage was lower than at midcycle for vastus lateralis (71% demi-pliés) and medialis (83%). Genu recurvatum > or = 10 degrees was observed at the beginning and end of demi-plié in all ballet dancers, but not in modern dancers. There was marked variation of EMG activity during demi-plié in the lateral gastrocnemius, medial gastrocnemius, gluteus maximus, hamstrings, and adductors. The results support the hypothesis that ballet and modern dancers have different patterns of muscle use in standing posture and demi-plié, which in part may be a result of differences in genu recurvatum and turnout between the two groups.

Adult↗

Prenatal correlates of indigent mothers' attitudes about spoiling their young infants: a longitudinal study.

The purpose of this study was to investigate factors associated with indigent mothers' attitudes about spoiling their young infants. Mothers who believe that young infants can be spoiled may be more likely to misperceive their infants' basic needs for nurturing and thus undermine their infants' sense of security and trust. One hundred twenty-nine consecutive pregnant women who were at approximately 15 weeks' gestation completed measures to assess depressive symptoms (Center for Epidemiologic Studies Depression Scale) and social support (Maternal Social Support Index). One hundred seventeen mothers (91%) completed a simple three-question Spoiling Index when their infants were about 1 month old. Fifty-eight percent were single, never married, 73% multiparous, 66% Euro-American, 28% African-American, and 84% at least 20 years old. Fifty-eight percent of mothers believed infants younger than 5 months old could be spoiled. After including maternal age, race, marital status, prenatal social support, and number of prenatal clinic visits in the hierarchical logistic regression model, "spoilers" were more likely to be primigravida mothers (odds ratio = 2.71; 95% confidence interval, 1.05 to 7.06) and more likely to be depressed during pregnancy (odds ratio = 2.83; 95% confidence interval, 1.29 to 6.19). Primigravida indigent mothers and mothers with higher levels of prenatal depressive symptoms are more likely to believe they can spoil their young infants.

Adult↗

Successful aging: how to help your patients cope with change.

Collaborative work between physicians and social workers can be very valuable in helping patients to "age successfully." For many patients, the medical consequences of chronic disease are compounded by social problems, such as isolation and loss of self esteem. Social workers attempt to help people cope with the stresses of aging by gaining some degree of control over their lives. Keys to successful aging include being flexible and adaptable in the face of change, being connected in a confidante relationship with at least one other person, and feeling that life has a purpose beyond mere survival. Social workers provide such mental health services as counseling, support, and conflict resolution. They can also assist in the time-consuming work of finding needed community resources.

Adaptation, Psychological↗

C-type natriuretic peptide receptors and signaling in rectal gland of Squalus acanthias.

Recent evidence suggests that the newly described natriuretic peptide, C-type natriuretic peptide (CNP), may be the circulating form of natriuretic peptide in the shark. In the shark CNP has a major site of action in the rectal gland, which augments chloride secretion in response to stimulation by volume loading or CNP infusion. We therefore examined the shark rectal gland for natriuretic peptide receptors and determined the presence of guanylate cyclase-linked receptors and non-guanylate cyclase-linked receptors for CNP in this tissue. CNP binds with uniform high affinity (dissociation constant of 78 +/- 11 pM) to receptors of high density (receptor density of 61 +/- 0.7 fmol/mg protein) in plasma membranes prepared from the rectal gland. By use of rat atrial natriuretic peptide (rANP) as a competing ligand, two classes of receptors become apparent in this population, both of which have similar affinity for CNP, but different affinities for rANP. The low-molecular-weight natriuretic peptide receptor-specific peptide, des-[Gln116,Ser117,Gly118, Leu119,Gly120]rANP-(102-121), binds to 50% of the receptors in the rectal gland, but fails to bind to the remaining 50% even at micromolar concentrations. Porcine brain natriuretic peptide (pBNP) binds with uniformly diminished affinity to all receptors, whereas the unrelated peptide, porcine vasoactive intestinal peptide, does not bind these receptors. The importance of the integrity of the ring structure of CNP is underlined by the significant loss of affinity when the peptide ring is opened.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of tributyltin chloride on vascular responses to atrial natriuretic peptide.

The effects of tributylin chloride (TBT) on vascular smooth muscle responses to norepinephrine, nitroprusside (SNP) and atrial natriuretic peptide (ANP) were studied in isolated aortic rings of rats. TBT did not interfere with norepinephrine-induced contraction or SNP-induced vasorelaxation. However, TBT produced a dose-dependent inhibition of ANP-induced vasorelaxation. Inhibition was not observed with inorganic tin chloride, SnCl2. The inhibition of vasorelaxation was accompanied by a parallel inhibition of ANP-induced cGMP generation. SNP-induced generation of cGMP was not affected by TBT. TBT did not interfere with binding of ANP to its receptor in bovine adrenal glands suggesting that the effects of TBT were mediated by direct interaction with membrane-bound guanylate cyclase.

Animals↗

Mechanisms of early death despite thrombolytic therapy: experience from the Thrombolysis in Myocardial Infarction Phase II (TIMI II) study.

Mechanisms of death among patients who died within 18 h of enrollment in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) study were analyzed. Of 3,339 patients enrolled, 32 died within the 1st 4 h and 31 died within the subsequent 14 h. Thirteen of the 63 patients had shock at enrollment; 22 had advanced hemodynamic compromise without shock and 28 initially had minimal to no compromise. Prior infarction was present in 16 patients (25%). Pump failure was responsible for 39 early deaths (62%), ventricular rupture for 10 (16%), arrhythmia for 8 (13%) and complications of therapy for 6 (10%). Nine of 720 patients randomized to immediate intravenous beta-adrenergic blocking agent therapy had an early death compared with 6 of 714 assigned to deferred beta-blocker therapy. Thus, mortality is highest in the early hours after myocardial infarction, even in patients treated with thrombolytic therapy and is most frequently due to pump failure. These results imply that efforts to reduce mortality during this critical time period should be directed at prevention, limitation or palliation of early pump failure.

Adrenergic beta-Antagonists↗

Diltiazem enhances potassium disposal in subjects with end-stage renal disease.

Seven subjects with end-stage renal disease (ESRD) who were anuric and dialysis-dependent were studied during a 28-hour interdialytic period to assess changes in plasma potassium. Plasma potassium, glucose, magnesium, aldosterone, and cortisol were measured every 4 hours. Eight normal subjects were similarly treated. Subjects with ESRD had a progressive increase in plasma potassium, in contrast to normal subjects who exhibited a characteristic diurnal variation. In ESRD, diltiazem significantly reduced the rate of increase in plasma potassium compared with placebo and resulted in a significantly lower net increase in potassium over the entire 28-hour period. Diltiazem did not affect plasma potassium in normal subjects. Diltiazem did not affect plasma aldosterone, cortisol, glucose, or magnesium. In conclusion, diltiazem reduced the rate of increase of plasma potassium during a 28-hour interdialytic period.

Adolescent↗

C-type natriuretic peptides stimulate chloride secretion in the rectal gland of Squalus acanthias.

Homologous shark C-type natriuretic peptide (sCNP) was infused as a bolus and as a constant infusion in the isolated perfused rectal gland of the same species, Squalus acanthias. sCNP was a potent stimulator of chloride secretion similar in its dose-response curve to vasoactive intestinal peptide. sCNP was equipotent with killifish CNP but more potent than human CNP (hCNP). Truncated and substituted, forms of hCNP were also capable of stimulation of chloride secretion in the order hCNP greater than hCNP (6-22) = [Gly9]hCNP greater than hCNP-(7-21). sCNP was more potent than human atrial natriuretic peptide (hANP), which was more potent than porcine brain natriuretic peptide. hANP-(31-67) was without effect. These studies suggest that sCNP may be the physiological regulator of rectal gland function. The receptor in the rectal gland is unknown but based on the order of potencies, position 4 in the NH2-terminal end and the ring itself are important for ligand effects.

Amino Acid Sequence↗

Downregulation of specific protein carboxylmethyltransferase immunoreactivity in human endometrial carcinoma.

Protein carboxylmethyltransferases (PCMT), enzymes that methylate free carboxyl groups of proteins, are involved in functional modification of various proteins including those of age-damaged proteins and the oncogenic ras proteins. Several species of PCMT are associated with these modifications. By using western blot analysis and specific antibodies raised against one type of PCMT, a 30-kilodalton (KD) cytosolic enzyme from Torpedo electric organ was identified in human erythrocytes and endometrium. The high specificity of the antibodies made it possible to compare levels of immunoreactive 30-KD PCMT protein in normal human endometria and endometrial carcinomas. Assays done on samples from 23 patients indicated the average levels of immunoreactive 30-KD PCMT in endometrial carcinomas was one fifth that of normal endometrium. The sensitivity of the assay was 83%, and its specificity was 90%. These results suggest that levels and activity of the 30-KD PCMT may be downregulated to maintain the phenotypic expression of the endometrial carcinoma. These assays may be used to assist in the detection of endometrial carcinomas.

Adult↗

The diurnal rhythm of plasma potassium: relationship to diuretic therapy.

Plasma potassium levels have been implicated in the genesis of cardiac arrhythmias, particularly in patients receiving diuretic therapy. The present study was undertaken to evaluate the stability of plasma potassium levels throughout a 28-h period. Normal volunteers (n = 8) and subjects with essential hypertension (n = 10) were studied in a clinical research center while receiving controlled dietary intakes. Plasma potassium followed a diurnal rhythm in both groups, with a peak level at 12 h and a trough level at 24 h. The average peak-to-trough difference was 0.62 +/- 0.05 mmol/L. Urinary potassium excretion also followed a diurnal rhythm, with the lowest excretory rate during the evening hours, when plasma potassium reached its nadir. Subjects with essential hypertension were restudied after 4 weeks of hydrochlorothiazide (50 mg/day) and then after an additional 4 weeks of hydrochlorothiazide (50 mg/day) and amiloride (5 mg/day). Hydrochlorothiazide alone reduced plasma potassium at all times of measurement without altering the diurnal rhythm. The combination of hydrochlorothiazide and amiloride resulted in higher plasma potassium levels in the morning, but did not significantly affect evening plasma potassium levels. The frequency of hypokalemia (K less than or equal to 3.0 mmol/L) was related to the time at which the plasma potassium was measured. We conclude that plasma potassium undergoes a diurnal rhythm and that diuretics shift this rhythm to uniformly lower values. This rhythm must be considered when defining the frequency of hypokalemia.

Adult↗

Home care for HIV disease: a community-based model.

In an effort to better meet the needs of the largest populations of HIV-infected individuals in the country, California instituted a state-funded home care pilot project that provides cost-effective care in a comforting and familiar setting.

Acquired Immunodeficiency Syndrome↗