Search PubMed⌕ Search

Biomedical subjects

M Benson

Publications and source records attributed to M Benson.

At least 109 records · Page 6Linked to original sources

Inhibition of growth of human breast carcinomas in vivo by somatostatin analog SMS 201-995: treatment of nude mouse xenografts.

Minced tumor fragments were xenografted into subcutaneous tissue of the lateral thoracic regions of young adult, virgin female nude mice to study the effects of somatostatin analog SMS 201-995 on growth of estrogen-dependent (MCF-7) and estrogen-independent (BT-20) human breast carcinomas. When tumors became palpable (6 to 10 days), mice were assigned randomly to receive either SMS (4 to 50 micrograms) or acetate buffer (0.2 ml) subcutaneously twice a day. For MCF-7, mean tumor volume was significantly lower on day 20 and days 30 through 50 in SMS-treated mice than in controls (p less than 0.05), and tumor doubling time was increased from 13.2 to 19.0 days. Calculated growth increment was significantly lower with SMS than with buffer treatment (1.1 +/- 0.1 vs 1.9 +/- 0.2) (p less than 0.001). For BT-20, mean tumor volume of SMS-treated mice was slightly, but not significantly, lower than that of controls; however, calculated growth increment was significantly lower for SMS treatment (3.2 +/- 0.3 vs 3.9 +/- 0.4) (p +/- 0.001), and tumor doubling time was increased from 4.0 to 5.8 days. For MCF-7, flow cytometric DNA analysis of tumor biopsy samples demonstrated a reduced G2 + M phase with SMS treatment. We conclude that SMS slows the growth of both MCF-7 and BT-20 human breast cancer xenografts in nude mice and that SMS may be clinically useful in the management of patients with breast carcinoma.

Animals↗

The Drosophila zeste protein binds cooperatively to sites in many gene regulatory regions: implications for transvection and gene regulation.

The Drosophila zeste protein binds in vitro to several sites in the white, Ultrabithorax, decapentaplegic, Antennapedia, and engrailed genes and to at least one site in the zeste gene itself. The distribution of these sites corresponds often with that of regulatory elements in these genes as defined by mutations or, in the case of white, by molecular analysis. A zeste binding site is frequently found in the immediate vicinity of the promoter. zeste binding sites are composed of two or more zeste recognition sequences T/CGAGT/CG. Isolated consensus sequences do not bind or footprint. Cooperative interactions are involved both in binding to a given site and between proteins bound at independent sites. zeste bound to one DNA molecule can in fact bind simultaneously to another DNA molecule. These results suggest a general role for zeste in bringing together distant regulatory elements controlling the activity of a target gene. In this model, transvection effects are a by-product of normal intragenic zeste action.

Animals↗

Gene expression during the early phases of regression of the androgen-dependent Shionogi mouse mammary carcinoma.

The effects of castration on gene expression were measured in the androgen-dependent Shionogi mouse mammary carcinoma. From 0 to 144 h after castration, polyadenylated RNA from the tumors was analyzed by Northern blotting for the expression of genes associated with cell maintenance (beta-actin and alpha-tubulin), cell growth and differentiation (c-fos and c-myc), and cell stress and death (heat shock 70 and TRPM-2). During the first 48-72 h after castration, the tumor continued to increase its mass but thereafter (72-144 h) began to regress. Throughout, the concentration of polyadenylated RNA recovered and the expression of both beta-actin and alpha-tubulin remained relatively constant, implying that in the surviving cells there are no major decreases in RNA synthesis. By comparison, c-myc exhibited a small increase in relative expression during the entire period examined, whereas c-fos displayed a transient peak at 12 h after castration, suggesting that this gene is acutely sensitive to androgen withdrawal. Heat shock protein 70 displayed a pattern similar to that of c-fos; however, the transient rise in the level of heat shock protein 70 expression could be induced by sham operations alone. The concentration of the transcripts encoding TRPM-2 rose only when tumor regression was most evident (72-144 h after castration). Thus, gene expression in the Shionogi carcinoma following castration can be grouped according to those genes which show little or no response, those which are acutely sensitive, and those which show a late effect and are more closely affiliated with cell death.

Animals↗

Zeste encodes a sequence-specific transcription factor that activates the Ultrabithorax promoter in vitro.

Zeste is a Drosophila regulatory gene that is required for transvection at the bithorax complex. Here we find that purified zeste protein binds to multiple sites just 5' of the initiation site of Ubx RNA. Zeste protein purified from Drosophila cells or from E. coli expressing the zeste gene activates Ubx transcription in vitro. This activation is dependent on the presence of zeste protein binding sites, as it is not observed with a Ubx promoter lacking these sites or with an Adh promoter. These results suggest that transvection involves regulatory elements that act at the level of transcriptional initiation and may be mechanistically similar to activation of transcription by enhancer elements, except that transvection occurs across paired chromosomes. These findings are consistent with the hypothesis that zeste may play a more important role in the normal regulation of Ubx and its other target genes than current genetic evidence implies.

Animals↗

MRI of multilocular cystic nephroma.

We report the magnetic resonance imaging (MRI) findings in 2 patients with multilocular cystic nephromas. Both underwent MRI immediately prior to resection. The images accurately reflected the morphology of the tumors: in each, the capsule was hypointense on all pulse sequences. Varied intensities of signal from the fluid in the visualized locules presumably represented differing concentrations of old hemorrhage and protein. In one case soft tissue elements became hyperintense on T2-weighted images. We speculate that MRI of multilocular cystic nephromas will produce imaging features that are highly suggestive, but not always pathognomonic, of the disease.

Adult↗

Conformational analysis of 9beta,19-cyclopropyl sterols: Detection of the pseudoplanar conformer by nuclear Overhauser effects and its functional implications.

Nuclear Overhauser difference spectroscopy and variable temperature studies of the 9beta,19-cyclopropyl sterols 24,25-dehydropollinastanol (4,4-desmethyl-5alpha-cycloart-24-en-3beta-ol) and cyclolaudenol [(24S)-24-methyl-5alpha-cycloart-25(27)-en-3beta-ol] have shown the solution conformation of the B/C rings to be twist-chair/twist-boat rather than boat/chair as suggested in the literature. This is very similar to the known crystal structure conformation of 9beta,19-cyclopropyl sterols. The effect of these conformations on the molecular shape is highly significant: the first conformation orients into a pseudoplanar or flat shape analogous to lanosterol, whereas the latter conformation exhibits a bent shape. The results are interpreted to imply that, for conformational reasons, cyclopropyl sterols can be expected to maintain the pseudoplanar shape in membrane bilayers.

Journal Article↗

Multiple primary neoplasms in association with prostate cancer in black and white patients.

The current study follows up the 983 patients who were diagnosed as having prostate cancer at the Columbia-Presbyterian Medical Center in New York City between 1970 and 1979 and of whom 106 (11.5%) developed a multiple primary malignant neoplasm (MPMN) in addition to their prostate cancer by January 1, 1986. Of the 283 black patients, 32 (11.3%) developed an MPMN involving 35 sites excluding prostate. Of the 636 white patients, 74 (11.6%) developed an MPMN in association with their prostate cancer. Comparing observed incidence rates to expected on the basis of SEER incidence data, two malignant tumors, urinary bladder cancer and malignant lymphoma, appeared to occur in excess in the present series of patients. The excess of urinary bladder cancer in our series could be explained by detection bias due to the routine use of cystoscopy. The excess incidence of lymphoma in our series appears significant but its etiology is unexplained.

Adult↗

The product of the Drosophila zeste gene binds to specific DNA sequences in white and Ubx.

Three different segments of the zeste coding sequence were inserted in an expression vector and antibodies were raised against the resulting zeste-beta galactosidase hybrid proteins. The antibodies were used to analyse the zeste protein produced in bacteria from a different expression vector containing the entire zeste coding region. The major products made in bacteria as well as the products of in vitro translation of zeste RNA migrate anomalously upon SDS--acrylamide gel electrophoresis. Specific DNA fragments from the white and Ubx gene co-immunoprecipitate with zeste protein. At least two independent zeste binding sites are found in a 250-bp interval of the white regulatory region that contains also the sites of wsp mutations, which are known to be deficient in zeste interaction.

Animals↗

Structure and sequence of the Drosophila zeste gene.

The zeste gene of Drosophila affects the expression of other genes in a manner that depends on the homologous pairing of the chromosomes bearing the target gene. Zeste mediates transvection effects, the ability of one gene to control the expression of its homologous copy on another chromosome. We have determined the structure of the zeste gene and several mutants bearing partial deletions and the sequence of the z+, z1, zop6 and z11G3 alleles. The predicted zeste protein has an unusual structure including runs of Gln, Ala and alternating Gln Ala. Contrary to expectations the z1, zop6 and z11G3 mutations can each be attributed to single amino acid changes. The analysis of the mutants suggests that the zeste gene product is required for normal expression of at least some genes and we argue that za mutants may have residual function.

Amino Acid Sequence↗

Intrathecal immunoglobulin production and minor motor seizures.

Five infants with idiopathic infantile minor motor seizures had an elevated immunoglobulin G (IgG) index ((cerebrospinal fluid IgG/serum IgG):(cerebrospinal fluid albumin/serum albumin)). The infants had prolonged prodromal symptoms, and bad prognosis. It is suggested that immunological mechanisms may contribute to the pathophysiology in certain cases of infantile spasms.

Adrenocorticotropic Hormone↗

Bilateral congenital pseudarthrosis of the olecranon.

A case of bilateral congenital pseudarthrosis of the olecranon is described. The clinical features, radiological appearance and prognosis are distinct from the type of congenital pseudarthrosis of the forearm reported previously. The lesion appeared to be a localised failure of ossification within the proximal ulnar metaphysis. Excision, stabilisation and bone grafting led to rapid fusion.

Child, Preschool↗

Epidural cord compression in association with genitourinary neoplasms.

The epidural compression secondary to genitourinary malignancies is relatively uncommon. Of 2118 patients who were diagnosed as having a genitourinary malignancy at the Columbia-Presbyterian Medical Center from 1970-1979, 21 are known to have developed an epidural cord compression by June 30, 1985 (16 from prostate, 1 from urinary bladder, and 4 from renal origin). The following items were reviewed in these 21 patients: age of the patient at diagnosis of the primary tumor; primary site of the genitourinary primary; time in months from the date of diagnosis of the genitourinary primary to the data of diagnosis of the spinal cord compression; methods of diagnosis; presenting symptoms and signs; treatment methods; and survival following the date of diagnosis of the compression. The distribution of location of the epidural metastasis in the current series is as follows: cervical-thoracic, 7%; thoracic, 73%; and lumbosacral, 20%. Skip metastases to the epidural space was the initial sign of malignancy in six patients (31.5%). Five patients (26%) with epidural cord compression survived at least 24 months following the date of diagnosis of their compression. Only two patients in this series with paraplegia (secondary to their compression) had improvement in ambulation following treatment of their compression: of these two patients, one had a prostate primary and the other a renal primary. The indications and techniques for surgery and radiotherapy are briefly described and early diagnosis and treatment are stressed.

Aged↗

The role of imaging studies in urinary tract infection.

Technology has permitted significant advances in the imaging and early diagnosis and treatment of many serious urinary tract infections. The armamentarium is vast, with CT scan, ultrasound, nuclear scan, and magnetic resonance imaging on the horizon, with more studies certainly to follow. Nothing, however, can replace the value of proper assessment of clinical signs and symptoms and the logical pursuit of a diagnosis with knowledge of the capabilities and deficiencies of each study.

Abscess↗

Measurement of liver volume using water delay ultrasonography.

A modification of the method of Carr et al. [1976] for the ultrasonic assessment of liver volume was devised for use with a UI Octoson water delay B mode echoscope, and 32 subjects without clinical history or signs of liver disease were examined. In 9 subjects the measurements were repeated by a separate observer. Comparison of the variance between observers and that between subjects showed that the precision of the method is within acceptable limits, the variance ratio (F) being 13.7 (p less than 0.001). The mean liver volume was 1,545.4 +/- (SD) 255 ml. This finding is in close agreement with previously published data. The liver volume was correlated with body weight, height, body surface area, and body mass index. The liver volume was found to correlate best with body weight using partial correlation analysis. This was in accordance with previously published data, with the exception of that of Koischwitz [1979]. However, variations in weight could only account for 0.43 of the variation in liver volume.

Analysis of Variance↗