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Biomedical subjects

M Samuels

Publications and source records attributed to M Samuels.

At least 55 records · Page 3Linked to original sources
PubMed1987

Dual task performance in children: generalized and lateralized effects of memory encoding upon the rate and variability of concurrent finger tapping.

Interference between concurrent tasks was used to investigate the brain basis of capacity limitations apparent when children encode information. Seventy-three right-handed children in Grades 1-4 engaged in speeded unilateral finger tapping while encoding a variable number of faces or numbers for subsequent recognition testing. With both face and number encoding, tapping rate decreased as memory load increased. Encoding numbers was more disruptive than encoding faces. Both encoding tasks slowed right-hand tapping more than left-hand tapping, relative to control tapping performance, but had only a bilateral effect on the variability of tapping. Although overall interference was less than that observed with a comparison task (i.e., speaking), the asymmetry of interference was comparable. The results suggest that cerebral lateralization for memory encoding, as well as for speech, is constant across the age range of 6-10 years. Findings regarding developmental change in overall capacity, however, are task specific: interference from speaking but not from memory encoding decreases with increasing age.

Attention↗
PubMed1986

Purification and characterization of a specific RNA polymerase II transcription factor.

Accurate transcription by RNA polymerase II has previously been shown to require a HeLa cell fraction designated [AB] in addition to other components (Samuels, M., Fire, A., and Sharp, P. A. (1982) J. Biol. Chem. 257, 14419-14427). A factor which substituted for HeLa [AB] was identified in chromatographic fractions from calf thymus and was purified an estimated 9,000-fold or more. The final calf thymus [AB] fractions contained three polypeptide species with molecular weights of 19,600, 19,100, and 12,800, whose appearance correlated with the transcription factor enzymatic activity. The intact factor had a molecular weight of 25,600-35,000 based on gel filtration and sedimentation analysis and could be inactivated by treatment with high temperatures or with N-ethyl-maleimide. [AB] did not stimulate nonspecific nucleotide incorporation by pure RNA polymerase II, but it did interact with factor [DB] and promoter template DNA to form a functional intermediate preceding accurate initiation. The calf thymus factor thus was homologous to HeLa [AB] by both physical and functional criteria. In contrast to a previous suggestion that this factor has properties associated with actin the highly purified active fractions did not contain detectable actin.

Actins↗
PubMed1986

Orchiectomy in advanced germ cell cancer following intensive chemotherapy: a comparison of systemic to testicular response.

A total of 16 patients with advanced germ cell cancer underwent initial chemotherapy that was followed by a delayed orchiectomy for an unrecognized primary in 3 and for life-threatening distant metastatic cancer in 13. Of these patients 13 had a complete and 3 had a partial remission at the time of the delayed orchiectomy. Of the former 13 patients 3 (23 per cent) had persistent viable tumor in the testis. To date all 3 patients have remained free of disease for more than 12, 20 and 30 months, respectively, without further therapy. One early relapse (1 month) was found in the remaining 10 patients with a complete remission and without viable disease in the testis. Of the 3 patients with a partial remission 1 had residual tumor in the testis and disease progressed despite further therapy. There was no evidence of tumor in the testis in the other 2 patients. These data document the presence of a differential response of germ cell tumors in the primary and metastatic sites. Post-chemotherapy orchiectomy for a suspicious primary tumor of the testis is necessary because of the risk of persistent primary disease. The post-chemotherapy pathological findings in the resected primary tumor do not reflect the systemic response.

Combined Modality Therapy↗
PubMed1986

Presentation rate effects on paired associate learning by attention deficit disordered children.

2 methods of varying presentation rate during paired associate learning were contrasted in attention deficit disordered (ADD) children. Previous studies have varied presentation rate across different (fixed rate) lists, and they have demonstrated that ADD children perform poorly at slower rates. In the present study, this method of presentation was contrasted with one in which half the items within a single list were presented at a fast rate and half at a slow rate. The debilitating effect of the slow rate was obtained in ADD children (but not in normal controls) only with the fixed list method. This finding suggests that the rate effects occur in ADD children because they are vulnerable to the experimental context created when items are presented at a slow rate over an extended time period.

Attention↗
PubMed1985

Plasma concentrations after oral or intramuscular vitamin K1 in neonates.

One hundred and seven healthy, breast fed infants received 1 mg vitamin K1 either at birth (orally or intramuscularly) or with the first feed (orally). Venous blood samples collected in the next 24 hours were assayed for plasma vitamin K1. In babies given the vitamin orally at birth, the peak median concentration (73 ng/ml) occurred at four hours. By 24 hours median plasma concentrations had fallen to 23 ng/ml and 35 ng/ml in the groups fed vitamin K1 at birth or with the first feed, respectively; this difference was not, however, significant. Plasma concentrations after intramuscular injection exceeded those in the oral groups at all comparable times, with a peak median concentration of 1781 ng/ml at 12 hours falling to 444 ng/ml at 24 hours. Since median plasma vitamin K1 concentrations 24 hours after oral administration were some 100 times and 1000 times greater than previously estimated adult and newborn values respectively, this study supports giving vitamin K1 orally at birth to well, mature babies to protect against early haemorrhagic disease of the newborn. Further studies are needed to determine the optimum dose for protection over subsequent weeks.

Administration, Oral↗
PubMed1984

Dinucleotide priming of transcription mediated by RNA polymerase II.

Mammalian RNA polymerase II was shown to utilize dinucleoside monophosphates for priming of promoter specific RNAs. In a reconstituted system containing purified polymerase and HeLa cell fractions, dinucleotides were incorporated by complementarity with template sequences at the in vivo cap sites of the adenovirus major late and adenovirus early region IV promoters. Incorporation was shown by label transfer experiments and by determining the size of 5'-terminal RNase T1-resistant oligonucleotides. All 16 dinucleotides were tested for priming of RNA chains at the major late promoter. RNA polymerase II initiated with various primers over a contiguous region of 9 bases, centered around the in vivo initiation site. We suggest that the polymerase drifts or oscillates over this region. Using a dinucleotide challenge protocol, the rate of initiation at the major late promoter was measured following preincubation of the template DNA with RNA polymerase II and factors. Initiation with ATP was 90% complete within the 1st min after addition of nucleotide triphosphates. Stimulation of transcription by dinucleotides was not observed, due to this rapid initiation. The 5'-hydroxyl terminus of dinucleotide-primed RNAs remained unmodified. Although transcripts initiated with ATP were rapidly capped in whole cell extracts, ATP-primed RNA synthesized in the reconstituted system retained free 5'-terminal phosphates. Thus, capping was not essential for synthesis of long runoff RNAs.

Adenosine Triphosphate↗
PubMed1984

Interactions between RNA polymerase II, factors, and template leading to accurate transcription.

Accurate transcription by RNA polymerase II has been shown to require multiple factors in addition to the purified polymerase. In this study, we use a reconstituted transcription system, consisting of purified RNA polymerase II and three essential HeLa cell chromatographic fractions, to study events leading to transcription from the adenovirus major late promoter. A preincubation-pulse-chase protocol resolves the reaction into events occurring before and after nucleotide addition. Preincubation of template with a mixture of RNA polymerase II and factors allows formation of "activated" complexes, which are defined by the ability to rapidly commence accurate transcription when presented nucleotides. Maximal activation requires that polymerase, template, and each of the three HeLa fractions be present during preincubation. The activated complexes are template associated, as shown by their inability to exchange onto a second template added during further preincubation. Similar protocols are used to define functional intermediates leading to the activated complex. A template-associated functional complex is formed during the preincubation of template with just two of the HeLa fractions. Polymerase can associate with this intermediate complex in the absence of the third HeLa fraction. In the accompanying paper, we describe a direct analysis of initiation by "activated" complexes.

Animals↗
PubMed1984

Endodermal sinus tumor of the mediastinum. Report of apparent cure in two patients with extensive disease.

Primary endodermal sinus tumor (EST) of the mediastinum has been regarded as a rare and rapidly fatal germ cell neoplasm. We describe two cases of extensive EST treated with a new high-dose sequential combination chemotherapy regimen (CISCA-VB) followed by radical surgical excision. They are alive at 11 and 20 months, respectively, postoperatively. These cases stand in marked contrast to previously reported series. A new approach to the management of this tumor is proposed.

Adult↗
PubMed1983

Fatal acute hyperparathyroidism and parathyroid carcinoma.

A 43-year-old man with parathyroid carcinoma died with hypercalcemia before a definitive diagnosis was made. The condition of patients with hypercalcemia may deteriorate rapidly, and delays in treatment may be fatal. Metastatic growth, not mitotic activity, is the best criterion for the pathologic diagnosis of parathyroid carcinoma.

Acute Disease↗
PubMed1983

Clinical pharmacology of intraarterial cis-diamminedichloroplatinum(II).

After intraarterial (30 patients) or i.v. (seven patients) administration of cis-diamminedichloroplatinum, X-ray fluorescence spectrometry was used to measure platinum concentrations in plasma and urine. Arteries infused included hepatic (seven patients), carotid (six patients), iliac (ten patients), brachial (three patients), and femoral (four patients). All patients received i.v. mannitol. Pharmacokinetic parameters after intraarterial administration were similar to those after i.v. administration, although differences existed for different intraarterial routes of administration. Mean for all patients combined were: Co, 2.67 +/- 0.97 (S.D.) microgram/ml; t1/2 beta, 71.1 +/- 26.6 hr; clearance, 0.72 +/- 0.25 liters/hr/sq m; total volume of distribution, 45.2 +/- 17.0 liters/sq m; C x t, 167 +/- 72 mg/hr/liter; and 24-hr urinary excretion, 20 +/- 10% of the administered dose. Intrahepatic infusion of the drug was associated with a significantly lower Co (1.88 +/- 0.50 g/ml) and C x t (140 +/- 25 mg hr/liter) and significantly higher clearance (0.91 +/- 0.24 liters/hr/sq m) and volume of distribution (67.6 +/- 4.6 liters/sq m) than administration by other routes, suggesting first pass extraction of drug by liver. In addition, an apparent minor late rise in serum platinum concentration may suggest enterohepatic recirculation of drug. High fluid intake was associated with a low Co and a high volume of distribution, consistent with expansion of the central compartment by fluids. Low serum albumin (less than 3.5 g/dl) was associated with significant shortening of the t1/2 beta (50.5 +/- 21.6 hr), suggesting that the amount of unbound filterable drug may possibly be higher in patients with low serum albumin concentrations. Plasma from veins draining an infused area has a higher Co and C x t during infusion than concurrent plasma from peripheral veins. Thus, intraarterial administration of cis-diamminedichloroplatinum results in increased drug exposure of tumor in the infused area without substantially decreasing exposure of systemic tumor.

Cisplatin↗
PubMed1982

Separation and characterization of factors mediating accurate transcription by RNA polymerase II.

A whole cell extract of HeLa cells was resolved through two successive chromatographic steps using an extension of the procedure of Matsui et al. (Matsui, T., Segall, J., Weil, P. A., and Roeder, R. G. (1980) J. Biol. Chem. 255, 11992-11996). RNA polymerase II and three of the resulting fractions were necessary and sufficient for accurate transcription of the adenovirus major late promoter. This accurate transcription was quantitated as a function of each of the required fractions, polymerase, and DNA. A linear range of response was observed in each case. Using the linear ranges for assay, it was possible to calculate net purifications and yields for each of the required transcriptional activities after chromatography. These activities were each shown to sediment with a distinct peak on sucrose gradients. The effects of variations in salt concentration, magnesium concentration, temperature, and reaction time were determined. High resolution analysis of runoff transcripts showed that the reconstituted system initiated transcription precisely at the adenovirus major late and early region IV promoters.

DNA-Directed RNA Polymerases↗
PubMed1982

Transcatheter intraarterial infusion of chemotherapy in advanced bladder cancer.

Bilateral internal iliac artery infusion of chemotherapeutic agents in patients with advanced bladder carcinoma, Stage D, resulted in a 50% response or greater in nine of 15 patients with a median survival, thus far, of 52 weeks. Hematuria was controlled in eight of ten patients, and pain was relieved in 12 of 15 patients. Three additional patients were treated as adjuvants after their residual tumor was removed surgically or irradiated before chemotherapy. Cis-diamminedichloroplatinum (CDDP) was infused at a dose of 80--120 mg/m2 over a 24-hour period. When CDDP failed or in the presence of impaired renal function, a combination of 5-fluorouracil (5-FU) infused intraarterially while Adriamycin and mitomycin C were delivered intravenously, salvaged two patients. Complications were tolerable, consisting of transient acute tubular necrosis in two patients, a lower extremity embolus in one, and skin reactions due to 5-FU in two patients.

Adult↗
PubMed1981

5-fluorouracil, adriamycin, and mitomycin-C (Hi-FAM) chemotherapy for adenocarcinoma of the lung.

Thirty patients with unresectable adenocarcinoma of the lung were treated with high doses of 5-fluorouracil, Adriamycin, and mitomycin-C (Hi-FAM). Objective responses were seen in ten patients (one complete and nine partial remissions). No patient with pleural disease responded to treatment. Responses were seen in all other sites of involvement including liver. In a subgroup of patients younger than 65 years, who had not had prior treatment, and who had a performance status of greater than 60 (Karnofsky), an overall response rate of 50% was realized. The overall median survival for responding patients was 10+ months while nonresponders had a median survival of 5.21 months. Patients who had had prior irradiation had a median survival of 4.81 months compared with patients who had not had any prior treatment, whose median survival was 8.45 months. Toxicity was substantial and included primarily bone marrow suppression and stomatitis. Elderly patients with poor performance status and prior treatment tolerated therapy less well. These results indicate that Hi-FAM is useful in selected groups of patients with advanced adenocrcinoma of the lung.

Adenocarcinoma↗
PubMed1981

Inhibition of transcription factor activity by poliovirus.

To study the poliovirus-induced inhibition of host-cell RNA synthesis, we prepared transcription extracts from mock-infected and poliovirus-infected HeLa cells. In contrast with the control extracts, poliovirus-infected cell extracts prepared 3 hr after infection were unable to transcribe specifically DNA templates recognized by RNA polymerase II. Accurate transcription by RNA polymerase III, however, was only slightly reduced. Supplementation of the infected cell extract with a crude preparation of transcription factors (S100) restored its ability to transcribe a polymerase II template specifically; supplementation with purified polymerase II had no effect. When the S100 was fractionated on a phosphocellulose column, the restoration activity eluted between 0.35 M and 1 M KCl. When we tested infected extracts for inhibitory activity by mixing uninfected and infected cell extracts, no in vitro inhibition of polymerase II transcription by the uninfected extract was evident. These results indicate that at least one factor required for specific transcription by polymerase II is deficient in extracts from poliovirus-infected cells.

HeLa Cells↗