Biomedical subjects
A Silverstone
Publications and source records attributed to A Silverstone.
Induction of 1-aminocyclopropane-1-carboxylate synthase mRNA by auxin in mung bean hypocotyls and cultured apple shoots.
Auxin is known to promote ethylene production in vegetative tissues by increasing the activity of 1-aminocyclopropane-1-carboxylate (ACC) synthase; therefore, we have studied the effect of auxins on ACC synthase mRNA expression. Total RNA was isolated from auxin-incubated cultured apple (Malus sylvestris Mill.) shoots or mung bean (Vigna radiata L.) hypocotyls. These RNAs and a set of oligonucleotide primers corresponding to two conserved amino acid sequences (SNPLGTT and MSSFGLV) found in ACC synthases isolated from other species were used for polymerase chain reaction-based amplification of DNA fragments encoding the ACC synthase-active site domain. We obtained and sequenced a 290-base pair cDNA fragment (pAA1) from cultured apple shoots and a 328-base pair cDNA clone (pMBA1) from mung bean hypocotyls. Comparisons of their deduced amino acid sequences with those of previously characterized ACC synthase cDNAs indicate that both fragments are, indeed, closely related to ACC synthase cDNA. Northern blot analyses further showed that the expression of these transcripts is regulated by auxin treatment. These data indicate that auxin induces ethylene production transcriptionally by increasing the ACC synthase transcripts. The pAA1 shares 46% amino acid sequence homology with ripening-regulated apple fruit ACC synthase, indicating that ripening-regulated and auxin-regulated ACC synthases are encoded by different genes. In mung bean hypocotyls, aminooxyacetic acid, a potent inhibitor of ACC synthase activity, promoted the expression of auxin-induced ACC synthase mRNA, but cycloheximide inhibited this induction.
Sequence of a cDNA coding for a 1-aminocyclopropane-1-carboxylate oxidase homolog from apple fruit.
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A randomized trial of carboplatin versus iproplatin in untreated advanced ovarian cancer.
Between August 1984 and October 1987, 120 patients with stage IC to IV epithelial ovarian cancer were randomly assigned to receive carboplatin (400 mg/m2) or iproplatin (300 mg/m2) every 4 weeks as initial treatment. Stratification was made according to International Federation of Gynecology and Obstetrics (FIGO) stage and according to size of residual disease after surgery. Response was evaluated after six courses when patients were restaged, with laparoscopy or laparotomy in clinical complete responders or those with no assessable disease. Treatment was then stopped in surgically proven complete responders. Patients with partial (PR) or minor response (MR) received a further six courses of their original drug at a reduced dose (carboplatin 300 mg/m2, iproplatin 225 mg/m2). Patients with stable (SD), progressive (PD), or recurrent disease were treated with cyclophosphamide (1 g/m2). The response rates were 63% (95% confidence interval [CI], 50% to 74%) for carboplatin and 38% (95% CI, 26% to 51%) for iproplatin. Fifteen patients were not assessable for response. The median survival was 114 weeks (95% CI, 82 to 233 weeks) for carboplatin patients and 68 weeks (95% CI, 48 to 82 weeks) for iproplatin patients (P = .008). The amount of residual disease after initial laparotomy was a prognostic factor for survival. Myelosuppression was the main toxicity and was greater with iproplatin. This study shows carboplatin to be more active than iproplatin in the treatment of ovarian cancer and less toxic. Few responses to cyclophosphamide occurred following either drug, implying resistance to the alkylating agent.
Surgical treatment of vulval carcinoma.
Carcinoma of the vulva is an uncommon genital tract malignancy which lends itself to surgical cure as long as due regard is paid to the tumour's histology and mode of spread. Modern surgical concepts have significantly reduced morbidity in this elderly group of patients.
Unsuspected streptococcal infection presenting with diarrhoea in late pregnancy.
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Hydroxylation of N-(Delta-Isopentenyl)adenine to Zeatin: Relative Activities of Organ Systems from Actinidia arguta.
By incubating explants from Actinidia arguta seedlings on a nutrient medium supplemented with 20 to 30 micromolar N(6)-(Delta(2)-isopentenyl)adenine (i(6)Ade) and then measuring zeatin (io(6)Ade) accumulation in tissues, the distribution of i(6)Ade hydroxylase activities in whole plants could be determined. Based on analyses with three entire plants, it is estimated that, as an organ system, roots contain approximately 68% of the plant's hydroxylase, while stems and leaves account for about 26% and 6%, respectively, of the total activity. Depending on the part of the root examined, hydroxylase activities ranged from 20 to 148 nanomoles io(6)Ade accumulated per gram fresh weight per 24 hours of incubation. Stem activities ranged from 17 to 165 nanomoles per gram fresh weight per 24 hours with the lowest activities being found at the tip. Leaf activities were substantially lower (1-10 nanomoles per leaf depending on position) than either root or stem.
Nucleic acid sequence and oncogenic properties of the HZ2 feline sarcoma virus v-abl insert.
Hardy-Zuckerman 2 feline sarcoma virus (HZ2-FeSV), isolated from a multicentric feline fibrosarcoma is a replication-defective acute transforming feline retrovirus which originated by transduction of feline c-abl sequences with feline leukemia virus (FeLV) and is known to encode a 110-kilodalton gag-abl fusion protein with tyrosine-specific protein kinase activity (P. Besmer, W. D. Hardy, E. E. Zuckerman, P. J. Bergold, L. Lederman, and H. W. Snyder, Nature (London) 303:825-828, 1983). The nucleotide sequence of the abl segment in the HZ2-FeSV genome was determined and compared with the murine and human v-abl and c-abl sequences. The predicted transforming protein consists of 344 amino acids (aa) of FeLV gag origin, 439 aa of abl origin, and at least 200 aa of FeLV pol origin (p110gag-abl-pol). The 1,317-base-pair HZ2-FeSV v-abl segment (fv-abl) corresponds to 5' abl sequences which include the region known to specify the protein kinase domain. The 5' 189 base pairs of fv-abl correspond to 5' c-abl sequences not contained in Abelson murine leukemia virus (MuLV) v-abl. The mouse c-abl exon which contains these segments was identified, and its nucleotide sequence was determined. Comparison of the predicted amino acid sequence of fv-abl with those of Abelson MuLV v-abl and c-abl revealed five aa differences. The 5' junction between FeLV and abl was found to involve a preferred region in FeLV gag p30 (P. Besmer, J. E. Murphy, P. C. George, F. H. Qiu, P. J. Bergold, L. Lederman, H. W. Snyder, D. Brodeur, E. E. Zuckerman, and W. D. Hardy, Nature (London) 320:415-421, 1986). A six-base homology exists at the recombination site between the parental FeLV and the c-abl sequences. The 3' junction between fv-abl and FeLV pol predicts an in-frame fusion of fv-abl and FeLV pol. A transformed cell line containing a truncated gag-abl-pol protein, p85, that lacks most of the FeLV pol sequences was obtained by transfection of NIH 3T3 mouse cells. This result implies that the pol sequences of the p110gag-abl-pol protein are dispensable for fibroblast transformation. To assess whether the fv-abl segment specifies the unique biological properties of HZ2-FeSV, we constructed a Moloney MuLV-based version of HZ2-FeSV, Mo-MuLV(fv-abl), in which the fv-abl sequences were contained in a genetic context similar to that in HZ2-FeSV.(ABSTRACT TRUNCATED AT 400 WORDS)
Biosynthesis of ferritin subunits from different cell lines of HL-60 human promyelocytic leukaemia cells and the release of acidic isoferritin-inhibitory activity against normal granulocyte-macrophage progenitor cells.
Biosynthesis of acidic isoferritins was investigated in human promyelocytic HL-60 cells, characterized by diploid (2C), tetraploid (4C) and mixed diploid--tetraploid (2C-4C) DNA cell lines. The three cell lines were studied for the biosynthesis of ferritin and its subunits and for the release of acidic isoferritin-inhibitory activity against normal CFU-GM before and after addition of DMSO. While the tetraploid and mixed diploid--tetraploid cell lines synthesized more H-(Mr = 21) than L-subunits (Mr = 19) after induction, the tetraploid line synthesized more H-subunit before and after induction, compared to the diploid line. The release of acidic isoferritin-inhibitory activity was greater before than after induction in both cell lines, but the tetraploid cell line released more acidic isoferritin-inhibitory activity consistent with its greater production of Mr = 21 subunit. However, after induction no inhibitory activity could be detected from the diploid cells and much less activity was detected with the tetraploid cells, suggesting that differentiation caused a decrease in production of acidic isoferritin-inhibitory activity.
The skin and T-cell differentiation.
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Ferritin synthesis by human T lymphocytes.
Mononuclear cells from peripheral blood of normal humans, unselected spleen cells from patients with Hodgkin's disease, and selected T and non-T lymphoid cells from normal peripheral blood and from the spleens of Hodgkin's disease patients were examined for de novo synthesis and secretion of ferritin. After precipitation of labeled lysates and supernatants from unseparated and selected T cells with antiserum to human liver ferritin, two bands were visible on sodium dodecyl sulfate-polyacrylimide gel analysis. The two bands were detected in molecular weight regions 19,000 and 21,000, which are thought to represent the L and H subunits of the ferritin molecule, respectively. The slower band (subunit H) was more radioactive than the faster band (subunit L). The H subunit is found in greater amounts in the serum of some tumor patients, but its cellular origin has not been established. The present findings indicate that cells of the immune system contribute to the synthesis and secretion of a ferritin molecule with a high proportion of H subunits.
Biosynthesis of murine terminal deoxynucleotidyltransferase.
An immunoprecipitation assay for measuring synthesis of murine terminal deoxynucleotidyltransferase (EC 2.7.7.31) has been developed using rabbit antiserum to calf terminal transferase. The antiserum precipitates a single Mr = 60,000 polypeptide (TdT-60) from all cell lines and tissues that contain enzymologically demonstrable terminal transferase. This polypeptide is not precipitated from labeled extracts of cells that lack terminal transferase by enzymological criteria. TdT-60 fractionates with terminal transferase during phosphocellulose chromatography and sediments with it in a sucrose gradient. TdT-60 is not detectably processed to lower molecular weight polypeptides, and terminal transferase activity sediments as a Mr = 60,000 activity; thus, we believe it to be the active form of terminal transferase. Using this assay we have demonstrated that terminal transferase is synthesized in both the murine thymus and the bone marrow at a rate proportional to its biochemically measured steady state level. After cortisone treatment of mice, the Mr = 60,000 polypeptide disappears from the thymus and then reappears as the thymus begins to be repopulated.
Maternal hypertension and intrauterine fetal death in mid-pregnancy.
An analysis of the 156 pregnancies which terminated spontaneously between 16 and 27 weeks gestation, inclusive, indicated that in 41 patients where fetal death was the primary event, maternal arterial pressure was raised in early pregnancy when compared with matched groups of women whose pregnancies had a successful outcome. Blood pressure in the 14th week of pregnancy in women with fetal death was significantly higher than in women with other types of mid-trimester abortion. It is suggested that maternal hypertension predisposes to intrauterine fetal death in the mid-trimester of pregnancy as it does in the third trimester.
On the criteria document process and job health and safety.
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