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S Singer

Publications and source records attributed to S Singer.

14 recordsLinked to original sources
PubMed1992

In vivo antitumor activity and metabolism of a series of 5-deazaacyclotetrahydrofolate (5-DACTHF) analogues.

This study compares the antitumor activity and metabolism of the purine de novo biosynthesis inhibitor 5-deazaacyclotetrahydrofolate and a series of analogues. All compounds have similar IC50 values for inhibition of MCF-7 cell growth, activity of glycineamide ribonucleotide transformylase, and methotrexate uptake by MOLT-4 cells, the latter a measure of cellular uptake potential. Only 5-deazaacyclotetrahydrofolate and the 2'-fluoro and 3'-fluoro analogues demonstrated significant inhibition of colon 38 adenocarcinoma or HCT-116 colon carcinoma growth in vivo. This correlated with the Km of these compounds for folylpolyglutamate synthetase. 5-Deazaacyclotetrahydrofolate and 2'-fluoro-5-deazaacyclotetrahydrofolate which displayed the strongest antitumor activity were detectable in colon 38 tumor tissue 24 hr after dosing and were present nearly exclusively as the polyglutamated species. These results indicate that polyglutamation represents a critical step in the in vivo antitumor activity of these compounds.

Acyltransferases↗
PubMed1992

Long-term salvageability for patients with locally recurrent soft-tissue sarcomas.

Between 1971 and 1988, 39 patients were referred because of local recurrence of soft-tissue sarcomas and data from their patient records were analyzed to determine the parameters governing local recurrence. Mean follow-up was 11.1 years, with a mean time to local recurrence of 22 months. Twenty-one patients had local recurrence only, without metastatic disease. Salvage was provided for 14 (67%) of these patients after reexcision of local recurrence, and all 14 patients remained free of disease (mean follow-up, 112 months). We conclude that (1) excisional biopsy of tumors larger than 3 cm leads to potential contamination of clean tissue planes, limits ability to achieve an adequate margin of resection, and may compromise the definitive excision, and (2) in patients with local recurrence only, there is a high rate of long-term salvage (67% for follow-up of 9.3 years) after radical compartmental excision with or without postoperative radiation therapy.

Adolescent↗
PubMed1992

Oral contraceptive type and functional ovarian cysts.

OBJECTIVE: We tested the hypothesis that multiphasic, low-dose monophasic, and high-dose monophasic oral contraceptives share a common protective effect against functional ovarian cysts. STUDY DESIGN: We conducted a cohort study using the automatic files of Maine Medicaid to assemble a population of 7462 women between the ages of 15 and 44 who were prescribed an oral contraceptive between Jan. 1, 1987, and Dec. 31, 1988. We included as cases 32 women with a principal diagnosis of a functional ovarian cyst confirmed by medical records as being greater than 20 mm in diameter. RESULTS: At comparison with the absence of an oral contraceptive prescription, we observed decreasing rates of functional ovarian cysts among women prescribed multiphasic pills (rate ratio 0.91, 95% confidence interval 0.3000 to 2.31), low-dose monophasic pills with less than or equal to 35 micrograms estrogen (rate ratio 0.52, 95% confidence interval 0.17 to 1.33), and high-dose monophasic pills with greater than 35 micrograms estrogen (rate ratio 0.24, 95% confidence interval 0.01 to 1.34). CONCLUSIONS: The protective effect of oral contraceptives against functional ovarian cysts reported previously for high-dose monophasic pills may be attenuated with newer pills of lower hormonal potency.

Adolescent↗
PubMed1991

Angiogenesis determines blood flow, metabolism, growth rate, and ATPase kinetics of tumors growing in an irradiated bed: 31P and 2H nuclear magnetic resonance studies.

Experimental tumors growing in irradiated tissue have been used to study the biological differences characteristic of locally recurrent tumors. Since the hypoxic cell fraction of tumors growing in irradiated tissue is increased and growth rate is slowed, these tumors are assumed to be metabolically deprived with hypoperfusion. In this study, we directly measured the effect of tumor bed irradiation on blood flow, growth rate, rate of nucleoside triphosphate (NTP) turnover, and metabolic state using 31P and 2H nuclear magnetic resonance, and an intradermal assay for angiogenesis. (NTP turnover refers to ATP-synthetase mediated NTP turnover that is visible to 31P nuclear magnetic resonance using the technique of saturation transfer.) A decrease in the number of small blood vessels perfusing tumors in a preirradiated bed was found. Most of the decrease was due to a loss of vessels with diameters less than 0.04 mm. When tumors growing in preirradiated tissue reached approximately 100 mm3 in volume, a high frequency of gross and microscopic necrosis and hemorrhage was already observed in most tumors. Consistent with these observations, the phosphocreatine/inorganic phosphate and nucleoside triphosphate/inorganic phosphate ratios were significantly lower in the tumors growing in a preirradiated bed compared with tumors in a nonirradiated bed. The blood flow rate was similar to control for tumors less than 100 mm3 (45.8 versus 40.5 ml/100 g/min, P = not significant), but was significantly lower than control for tumors greater than 100 mm3 (40.4 versus 12.2 ml/100 g/min, P less than 0.01). The NTP turnover rates correlated (P less than 0.005, r = 0.66) with the volume doubling rate (1/tumor volume doubling time), but for tumors approximately 100 mm3 in size neither the volume doubling rate nor the NTP turnover rate of tumors growing in an irradiated bed was statistically lower than control [NTP turnover: 14 +/- 3%/s versus 9 +/- 2%/s; volume doubling rate: 0.47 +/- 0.07/day versus 0.33 +/- 0.04/day (mean +/- SE)]. A large intertumor variability of all metabolic parameters was observed.

Adenosine Triphosphatases↗
PubMed1990

Lack of efficacy of water-suppressed proton nuclear magnetic resonance spectroscopy of plasma for the detection of malignant tumors.

Water-suppressed proton nuclear magnetic resonance (NMR) spectroscopy of plasma has been proposed by Fossel et al. (N Engl J Med 1986; 315:1369-76) as a technique for detecting malignant tumors. In their analysis, plasma samples from patients with cancer were clearly distinguished from those of normal subjects by measuring and averaging the methyl and methylene line widths of plasma lipoproteins in NMR spectrums. To evaluate this diagnostic procedure further, we collected and analyzed by NMR spectroscopy 145 samples of plasma from patients who served as controls, most of whom were undergoing orthopedic or cardiac surgery (n = 66); patients with a variety of untreated malignant tumors (n = 25) or treated malignant tumors (n = 18); and patients with hyperplastic or "premalignant" diseases, such as benign prostatic hyperplasia and ulcerative colitis (n = 36). All the samples were coded, and NMR spectroscopy was performed without knowledge of the patients' clinical status. There were no significant differences in the NMR line widths among the four study groups (P greater than 0.05 for all pairwise comparisons). The specificity and sensitivity of this method for distinguishing the control patients (mean line width [+/- SD], 44.0 +/- 7.4 Hz) from those with untreated cancer (43.8 +/- 6.9 Hz) were poor, with a false positive rate of 52 percent (34 of 66) and a false negative rate of 56 percent (14 of 25). Inverse correlations of line widths with age (P less than 0.01) and with the plasma triglyceride level (P less than 0.001) were detected. We conclude that NMR spectroscopy of plasma is not an accurate test for the detection of malignant tumors.

False Negative Reactions↗
PubMed1990

Atrial natriuretic factor alters phospholipid metabolism in mesangial cells.

The mechanism for the vasorelaxant effect of atrial natriuretic factor (ANF) remains to be clarified. Recent evidence suggests that this agent can antagonize the action of angiotensin II (ANG II) by affecting intracellular calcium metabolism. The biochemical basis for this phenomenon was investigated in cultured rat mesangial cells (MCs), a preparation which exhibits the contractile properties of smooth muscle cells and is responsive to ANG II and ANF. Preincubation of MCs with ANF significantly inhibited ANG II-induced release of inositol trisphosphate (IP3) resulting from hydrolysis of phosphatidylinositol 4, 5-bisphosphate. Similarly, ANG II-stimulated increases in cytosolic free Ca2+ [( Ca2+]i), 45Ca efflux, as well as 45Ca influx were diminished by ANF. In addition, these alterations in Ca2+ kinetics were associated with ANF-mediated antagonism of ANG II-induced phospholipid turnover and prostaglandin (PG) E2 release. Sodium nitroprusside (SNP), which augmented guanosine 3',5'-cyclic monophosphate (cGMP) accumulation to a degree comparable to ANF, likewise inhibited ANG II action on the phosphoinositide (PI) pathway, Ca2+ regulation, and PGE2 production. Collectively our results indicate that the effects of ANF on [Ca2+]i in MCs relate to cGMP-induced alterations of PI metabolism. In this fashion cGMP-elevating agents may influence a variety of calcium-dependent biochemical pathways including prostaglandin synthesis.

1-Methyl-3-isobutylxanthine↗
PubMed1978

[Gastric polypoid heterotopy in the small intestine].

We present a 14 year old girl with a two years' history of colicky abdominal pain associated with the palpation of a tumor in the left upper quadrant of the abdomen. During these two years, the pain and the tumor appeared and disappeared spontaneously several times. In the operation we found a jejunojejunal intussusception, the head being a sessile polyp placed 20 cm from the ligament of Treitz. The pathological examination showed a polyp formed by mucosa similar to the gastric one with chief and parietal cells. We discuss the clinical pictures that can be associated with this pathological entity in this uncommon localization in opposition to the more common settling in Meckel's diverticulum.

Adolescent↗
PubMed1976

Annuities.

Explore the source record for details and available documents.

Investments↗
PubMedDate not supplied

Psychological aspects in children and adolescents with hypopituitarism.

Psychological studies in children with stunted growth have partly shown inconsistent results due to heterogeneity of samples and the use of non-standardized test procedures. We have examined patients with proven hypopituitarism using a selection of standardized and age-related psychological tests. Forty-eight patients, 32 male, 16 female, age 6 to 26 years with isolated growth hormone deficiency (n = 22) and multiple pituitary deficiencies (n = 26) were investigated. The patients had had hormonal substitution therapy for 0.1-16.8 years. Test procedures included evaluation of intelligence and various personality parameters. Full score IQ was in the average range. Despite these findings a high percentage of patients had delayed schooling or had to repeat a class. They were normal regarding emotional balance and frustration tolerance and did not show any tendency towards depression or psychosomatic disorders. Social behavior was characterized by an infantile attitude toward their personal environment. The patients showed a tendency to avoid aggressiveness in frustrating situations. In contrast to the results of these tests, a non-standarized interview demonstrated that the majority of patients had serious problems because of their short stature, including difficulties in finding social contacts. Continuous medical and psychological guidance is therefore recommended.

Adolescent↗