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Biomedical subjects

E C Martin

Publications and source records attributed to E C Martin.

At least 19 recordsLinked to original sources
PubMed1999

Quantitative PCR analysis of c-erb B-2 (HER2/neu) gene amplification and comparison with p185(HER2/neu) protein expression in breast cancer drill biopsies.

A PCR assay using capillary electrophoresis was designed for the detection of c-erbB-2 gene amplification in alcohol-formalin-acetic acid (AFA)-fixed, paraffin-embedded biopsies from 81 consecutive breast tumors. c-erbB-2 expression was analyzed in the same samples using immuno-histochemistry (IHC). In the competitive PCR assay, a single pTag plasmid containing a 4-nucleotide (nt)-deleted copy of a 124-nt sequence of c-erbB-2 and a 4-nt-deleted copy of a 120-nt sequence of GAPDH was co-amplified with genomic DNA extracted from 3 10-micrometer-thick tissue sections of the tumor biopsy. The percentage of tumor cells in the biopsy specimen and the percentage of tumor cells stained with the membrane anti-c-erbB-2 monoclonal antibody CB11 were recorded by a single pathologist on 2 consecutive sections. Among 81 consecutive tumor biopsies assayed by PCR, 21 (26%) displayed unequivocal c-erbB-2 amplification (actual gene copy number, AGCN > 4), 47 (58%) displayed no c-erbB-2 amplification (AGCN </= 2) and 7 (9%) could not be analyzed due to an insufficient amount of DNA. Six samples (7%) were considered inconclusive since the percentage of tumor cells was <20%. Analysis of c-erbB-2 expression by IHC showed that among the 21 amplified specimens 15 displayed strong staining, while all non-amplified samples (47) displayed no or only weak staining. The concordance of the 2 techniques was 91%. We conclude that c-erbB-2 gene amplification can be accurately quantitated by competitive PCR performed on small, fixed and embedded tumor samples.

Adenocarcinoma↗
PubMed1998

Complementary surgical/interventional techniques for nonresective management of "inoperable" aneurysms: a second look.

Induced thrombosis ("nonresective" therapy) of aortic aneurysms by distal arterial ligation, coil/wire embolization, and extraanatomic bypass was devalued by anecdotal reports emerging during the mid-1980s. Nevertheless, we have recently found the technique to be life-saving in occasional cases and worth revisiting. Since 1990, standard aortic aneurysm repair has been performed in 231 patients (99.1% survival), endovascular aortic aneurysm repair in 6 patients (83.3% survival), and combined surgical/interventional "nonresective" repair of a variety of aneurysms in 10 patients (100% survival). Mean age of the group was 67.9 years. Repair was performed for aortoiliac aneurysms (4), common iliac aneurysms (3), internal iliac aneurysms (2), and a large proximal subclavian artery pseudoaneurysm (1). Four of the patients had been explored and declared to be "inoperable" (retroperitoneal fibrosis) prior to transfer to the Columbia-Presbyterian Medical Center. All patients survived. Aneurysm rupture has not occurred in any patient, but one patient with a presumably thrombosed subclavian pseudoaneurysm presented 26 months postcoil-induced thrombosis with progressive aneurysm enlargement due to incomplete aneurysm thrombosis and required repair using circulatory arrest. Eight of the patients remain alive (80%) at a mean follow-up of 40.3 months (range 14-88 months). Two patients died of malignancy (30 months) and cardiac disease (15 months). It is concluded that combined surgical/interventional techniques can be life-saving in the rare instances when conventional or endovascular aneurysm repair is not advisable but that complete aneurysm thrombosis is essential and occasionally difficult to achieve. Since small proximal portions of the aneurysm may remain patent and not be visualized on magnetic resonance imaging (MRI) or computed tomography (CT) scans, contrast angiographic documentation of complete aneurysm thrombosis is essential prior to hospital discharge and close follow-up is necessary to ascertain long-term adequacy of the repair. Incomplete thrombosis is suspected as a major factor in earlier reports of aneurysm rupture after seemingly successful nonresective therapy.

Aged↗
PubMed1998

Estrogen receptor negative and progesterone receptor positive primary breast cancer: pathological characteristics and clinical outcome. Institut Curie Breast Cancer Study Group.

The expression of estrogen (ER) and progesterone (PgR) receptors was analyzed in a retrospective series of 3000 patients who had operable primary breast cancer. Patients were stratified according to ER and PgR status and the study was focused on the two groups (ER-PgR+ and ER-PgR-) of patients whose tumors contained low levels of ER (< 15 fmol/mg protein), regarding potential response to endocrine therapy. The comparison of clinical or histological characteristics between ER-PgR+ and ER-PgR- patients was analyzed as well as the disease-related death and survival. The mean follow-up was 86.3 months. Among the 529 ER-patients, 62 were PgR+ (12%), whereas 467 were PgR- (88%). The ER-PgR+ and ER-PgR- populations represented 2% and 15.6% of the overall population, respectively. In ER- tumors, the PgR status was significantly related to: age, menopausal status, tumor size, SBR grade, and histological type, but not to the type of surgical treatment or to lymph node involvement. ER-PgR+ tumors had smaller size (64% T1 vs 43%) (p=0.004) and were more frequently grade I (28% vs 12%) than ER-PgR- tumors (p < 0.001). In addition, the patients with ER-PgR+ tumors were significantly younger (49.4 years vs 58.4 years; p < 0.0001), and were more frequently premenopausal (76% vs 36%, p < 0.001). The disease-free interval and the metastasis-free survival tended to be worse for ER-PgR- than for ER-PgR+ patients, but the difference was not statistically significant at 10 years. However, a small but significant difference in overall survival, in favor of the PgR+ group, was observed between the two groups during the first 5 years (p=0.03). We conclude that in combination with ER, PgR status defines a group of patients with clinical and biological specificity, which could be considered for specific endocrine therapy.

Adult↗
PubMed1994

Directed overexpression of suppressor 2 of zeste and Posterior Sex Combs results in bristle abnormalities in Drosophila melanogaster.

Three dominant second-chromosome rearrangement mutations in Drosophila melanogaster, Aristapedioid1 (Arp), vestigial-Depilate (vgD), and vestigial62 (vg62), result in developmental abnormalities of the bristle sense organs on the notum, abdomen, legs, and wing margin. The bristle abnormalities are associated with overexpression of Suppressor 2 of zeste (Su(z)2). We constructed and transformed into flies Hsp70:cDNA constructs for Su(z)2 and the related and neighboring Polycomb group (Pc-G) gene Posterior Sex Combs (Psc). Heat shock-induced overexpression of these two genes (hs-Su(z)2 and hs-Psc) resulted in similar bristle abnormalities that in a developmental stage-specific manner mimicked those seen with the three rearrangement mutations. In addition, hs-Psc overexpression at white prepupae was lethal. The bristle abnormalities are reminiscent of those seen with reduced function of Notch, a neurogenic gene. We found that hs-Su(z)2 overexpression reduced the expression of a lac z enhancer trap in the neurogenic gene neuralized. Previous experiments found that loss of function mutations in Su(z)2 resulted in no bristle abnormalities. Analysis of Psc mitotic clones revealed no essential function of Psc in bristle development. Antibody staining of salivary gland polytene chromosomes showed that after heat shock induction of hs-Psc, Psc protein binds ectopically to hundreds of polytene chromosome loci. These data suggest that the bristle abnormalities seen with overexpression of Su(z)2 and Psc may result from altered expression of genes involved in bristle sense organ development that are not normal regulatory targets of these genes.

Animals↗
PubMed1993

The Polycomb group gene Posterior Sex Combs encodes a chromosomal protein.

The Posterior Sex Combs (Psc) gene of Drosophila has been studied at the molecular level both because it is a Polycomb group (Pc-G) gene and hence required for the maintenance of segmental determination, and because it is the Drosophila homolog of the murine bmi-1 oncogene. Although genetic interactions indicated that Psc functioned as a Pc-G gene, the zygotic mutant phenotype of Psc showed little evidence of segmental transformations. We have examined mutant embryos derived from a mutant maternal germ line and found a stronger mutant phenotype, indicating that the weak zygotic phenotype of Psc is due to maternal rescue. We have found that Psc RNA accumulates in developing oocytes and this maternal RNA is presumably responsible for the maternal rescue. We have studied the expression of the Psc gene at both the RNA and protein levels. On northern blots, we find evidence for two Psc mRNAs and, on western blots, we find evidence for two Psc proteins that are altered either in abundance or size in Psc mutants. The Psc protein accumulates in all regions of the embryo and also in many tissues in a variety of developmental stages. In all cases, it is nuclear, as is its mammalian homolog, the bmi-1 protein. On polytene chromosomes, we find Psc at 45 chromosomal loci where two other Pc-G proteins are present.

Animals↗
PubMed1991

Drosophila genes Posterior Sex Combs and Suppressor two of zeste encode proteins with homology to the murine bmi-1 oncogene.

The Polycomb group (Pc-G) genes are needed to maintain expression patterns of the homeotic selector genes of the Antennapedia (Antp-C) and bithorax (bx-C) complexes, and hence for the maintenance of segmental determination. We report the predicted protein sequence of the Pc-G gene Posterior Sex Combs (Psc), and of the neighbouring and related gene Suppressor two of zeste (Su(z)2). Both genes encode large proteins that contain a 200 amino-acid domain identical over 37.4% that is also conserved in the murine oncogene bmi-1. At the amino terminus of this domain is a cysteine-rich sequence that has been proposed as a novel type of zinc finger.

Amino Acid Sequence↗
PubMed1991

Phenotypic consequences and genetic interactions of a null mutation in the Drosophila Posterior Sex Combs gene.

The Posterior Sex Combs (Psc) gene of Drosophila is a member of the Polycomb (Pc) group of transregulatory genes. Previous analyses of the function of this gene in Drosophila embryogenesis have been hampered by the lack of a null mutation. We recently isolated a mutation that deletes the 5' end of the Psc gene. This allele appears to be a null mutation, and we have used it to determine the Psc zygotic null phenotype and to look at the interactions of a null allele of Psc with five other Pc group mutations. We find evidence for transformations along both the anterior-posterior and dorsal-ventral axes in embryos of a variety of genotypes that include a null mutation in Psc. The phenotypes of embryos that are doubly mutant for a null allele of Psc and a mutation in a second Pc group gene show dramatic synergistic effects, but in their specifics they are dependent on the identity of the second Pc group gene. This is different from the relatively uniform phenotypes seen among double mutants that contained the allele Psc1, which has both gain and loss of function properties. The differences in the phenotypes of the doubly mutant embryos allow us to eliminate one class of molecular models to explain the dramatic synergism seen with mutations in this group of genes.

Animals↗
PubMed1991

Molecular genetics of the Posterior sex combs/Suppressor 2 of zeste region of Drosophila: aberrant expression of the Suppressor 2 of zeste gene results in abnormal bristle development.

We report the molecular characterization of the Posterior sex combs-Suppressor 2 of zeste region of Drosophila melanogaster. The distal breakpoint of the Aristapedioid inversion divides the region into two parts. We have molecularly mapped the lesions associated with several loss of function mutations in the Polycomb group gene Posterior sex combs (Psc) proximal to this breakpoint. In addition, we have found that lesions associated with several loss of function mutations in the Suppressor 2 of zeste [Su(z)2] gene lie distal to this breakpoint. Since the breakpoint does not cause a loss of function in either gene, no essential sequences are shared by these two neighboring genes. There are three dominant gain of function mutations in the region that result in abnormal bristle development. We find that all three juxtapose foreign DNA sequences upstream of the Su(z)2 gene, and that at least two of these mutations (Arp1 and vgD) behave genetically as gain of function mutations in Su(z)2. Northern and in situ hybridization analyses show that the mutations result in increased accumulation of the Su(z)2 mRNA, which we argue is responsible for the bristle loss phenotype.

Animals↗
PubMed1990

Obstruction of the Roux limb after portoenterostomy for biliary atresia: a delayed complication.

We report the case of a 5-year-old girl who underwent a Kasai portoenterostomy for extrahepatic biliary atresia. The conduit was exteriorized until 11 months of age. She was doing well, with stable portal hypertension until she suddenly developed jaundice, acholic stools, and bacteremia not responsive to a course of steroids and intravenous antibiotics. Suspecting obstruction at the site of the previously exteriorized anastomosis, a percutaneous cannulation of the conduit was performed. Catheterization of the conduit obstruction unkinked it and reestablished bile flow. She has remained anicteric with stable liver function.

Anastomosis, Roux-en-Y↗
PubMed1990

Gianturco-Rosch biliary stents: preliminary experience.

Results of long-term follow-up are reported for nine patients who underwent placement of Gianturco-Rosch expandable metallic stents. Seven patients had malignant disease. The average duration of patency was 7 months. In one patient with inactive primary sclerosing cholangitis (PSC), the stents remained patent at 22 months, but recurrent stent closure was seen in a second patient with PSC. In the patient population studied, no advantages were seen with use of the stents; however, they may have an application in certain patients with benign disease.

Adenoma, Bile Duct↗
PubMed1989

Maintaining quality of life after palliative diversion for malignant ureteral obstruction.

The records of 71 consecutive patients who underwent percutaneous nephrostomy for malignant ureteral obstruction were reviewed. The average post-nephrostomy survival time was seven months, of which 25% was spent in the hospital. When comparing these figures to older studies of open nephrostomy, the percutaneous procedure is associated with less morbidity and an increased percentage of time spent at home (75% compared to 36%). Long-term survival, however, is still poor, with only 25% of patients alive at one year. We suggest that the criteria previously adopted for open nephrostomy generally remain appropriate for patients being considered for percutaneous urinary diversion.

Adult↗
PubMed1989

Percutaneous drainage of intra-abdominal abscesses following abdominal trauma.

Between January 1, 1984, and June 30, 1987, we performed percutaneous catheter drainage (PCD) of 28 intra-abdominal abscesses in 21 postoperative trauma patients. During this period only three patients had abdominal re-exploration for drainage of abdominal abscess. The PCD patients were predominantly young men who had sustained penetrating abdominal injuries (81% GSW or SW; 19% MVA). Seventeen (81%) patients had multiple abdominal organ injuries with the colon being the most frequently injured (57%). Multiple abscesses were identified in 33% of the patients. All 21 patients had successful treatment of their abscesses by PCD alone. There was one complication (4.8%) from PCD (pneumothorax) and no deaths in this group. Our data suggest that in most cases, PCD can be safe, effective, and definitive treatment for postoperative intra-abdominal abscesses following abdominal trauma. We recommend PCD in all postoperative trauma patients who develop accessible abdominal abscesses before resorting to re-exploration.

Abdominal Injuries↗
PubMed1989

Percutaneous transjejunal approaches to the biliary system.

The authors report 10 cases in which various retrograde manipulations in the biliary tract were performed via percutaneous access from the jejunum in patients who had previously undergone Roux-Y biliary surgery. The first cases involved attempted retrograde cholangiography through the jejunal limb in children who had undergone Roux-Y portoenterostomies, followed by cases of percutaneous placement of U tubes and an attempt at percutaneous creation of an hepaticojejunostomy. When a limb from the Roux-Y has been brought to the skin and marked with clips, jejunal puncture is easily performed, is well tolerated by patients, and may be repeated frequently. It also appears that after Roux-Y choledochojejunostomy, the Roux-Y limb is fixed and may be punctured with relative safety. Since access from below is more favorable for intrabiliary manipulations, the transjejunal approach expands the armamentarium of the interventional radiologist in the combined radiologic and surgical management of complex biliary disease.

Adolescent↗