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Biomedical subjects

G Coppola

Publications and source records attributed to G Coppola.

At least 73 records · Page 4Linked to original sources
PubMed1996

Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions.

PURPOSE: To assess the interobserver agreement on the diagnosis and classification of cutaneous melanoma. MATERIALS AND METHODS: A set of 140 slides of cutaneous melanoma, including a small subset of benign pigmented skin lesions, were circulated to four experienced histopathologists. The kappa statistic for multiple ratings per subject was calculated using the method described by Fleiss. RESULTS: The kappa value on the diagnosis of cutaneous melanoma versus benign lesions was 0.61. There was some discordance on the diagnosis in 37 of 140 cases (26%). For the histopathologic classification of cutaneous melanoma, the highest kappa values were attained for Breslow thickness (kappa = 0.76) and presence of ulceration (kappa = 0.87). The agreement was generally poor for other histologic features, such as level of dermal invasion (kappa = 0.38), presence of regression (kappa = 0.27), and lymphocytic infiltration (kappa = 0.27). CONCLUSION: Our study suggests considerable disagreement among pathologists on the diagnosis of melanoma versus other pigmented lesions. Tumor thickness and presence of ulceration are the most reproducible histologic features of cutaneous melanoma.

Humans↗
PubMed1995

Migrating partial seizures in infancy: a malignant disorder with developmental arrest.

Fourteen infants of both sexes had a previously unreported epileptic condition characterized by nearly continuous multifocal seizures. The first seizures occurred at a mean age of 3 months, without antecedent risk factors. At 1 to 10 months, the seizures became very frequent. They were partial with variable clinical expression, and the EEG showed that the discharges randomly involved multiple independent sites, moving from one cortical area to another in consecutive seizures. Although their topography varied, the EEG ictal pattern of each seizure was very similar. It consisted of rhythmic alpha or theta activity which spread to involve an increasing area of the cortical surface. Patients regressed developmentally and became quadriplegic with severe axial hypotonia. Three patients died at age 7 months and at age 7 and 8 years, respectively. Seizures were controlled in only 2 patients, and only 3 children resumed psychomotor development. Extensive investigation failed to determine an etiology, and there was no familial recurrence. Neuropathological examination of the brain in two cases showed only severe hippocampal neuronal loss and accompanying gliosis.

Anticonvulsants↗
PubMed1995

[Medicine as ars in the Roman world. Its advance from sacral to secular approach, its trading and public diffusion: socio-political considerations and their legal consequences].

The close linkage between empiric knowledge and its magic religious background in the archaic period appears clearly as a main feature characterizing the medical ars at its beginning, at least till it advances to a full secular approach during the fifth and fourth century B.C. The medical knowledge, which had been a privileged inheritance of the ruling class underwent a rapid transformation with the rise of the Roman Empire and its hegemonic politics that reached its climax during the Punic wars. As it was spread to all social classes it achieved an ever increasing importance leading to its specialisation and trading. This socio-political change had repercussions on the legal field: indeed conventiones concerning medical service came into effect. As far as action was concerned, doctors were permitted to avail themselves of the cognitio extra ordinem in order to get the rewards they were entitled to. The application of the legal tool cognition was however a device embedded in a set of other remedies aiming at granting rewards and incentives i.e. privilegia and salarium. Their development over the period of the Roman Empire was linked with a growing monopoly run by the supreme authority.

Commerce↗
PubMed1994

Oligonucleotides with novel, cationic backbone substituents: aminoethylphosphonates.

Oligonucleotide (2-aminoethyl)phosphonates in which the backbone consisted of isomerically pure, alternating (2-aminoethyl)-phosphonate and phosphodiester linkages have been prepared and characterized. One of these single isomer oligonucleotides (Rp) formed a more stable duplex with DNA or RNA than its corresponding natural counterpart. Hybrid stability was more pH-dependent, but less salt-dependent than a natural duplex. The specificity of hybridization was examined by hybridization of an oligonucleotide containing one (2-aminoethyl)phosphonate to oligonucleotides possessing mismatches in the region opposite to the aminoethyl group. In contrast to oligonucleotides containing (aminomethyl)-phosphonate linkages, oligonucleotide (2-aminoethyl)phosphonates were completely stable to hydrolysis in aqueous solution. These oligonucleotides were resistant to nuclease activity but did not induce RNase H mediated cleavage of a complementary RNA strand. Incubation in a serum-containing medium resulted in minimal degradation over 24 hours. Studies of cell uptake by flow cytometry and confocal microscopy demonstrated temperature dependent uptake and intracellular localization. (2-Aminoethyl)phosphonates represent a novel approach to the introduction of positive charges into the backbone of oligonucleotides.

Aminoethylphosphonic Acid↗
PubMed1994

Characterization of glycosylated and catalytically active recombinant human alpha-galactosidase A using a baculovirus vector.

Fabry disease is an X-linked inborn error of glycolipid metabolism caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GalA; EC 3.2.1.22). In order to obtain large quantities of this human enzyme for physical characterization and for the development of new approaches for enzyme therapy, we constructed derivatives of the Autographa californica nuclear polyhedrosis virus that produce the human enzyme. The recombinant GalA (re-GalA) is produced at high levels, and is active with both the artificial substrate, 4-methylumbelliferyl-alpha-D-galactopyranoside, and the natural in vivo substrate, trihexosylceramide. The purified re-GalA is glycosylated and is taken up by normal and Fabry fibroblasts in cell culture. Mass spectral analysis of total monosaccharides released by hydrazinolysis indicates that it contains fucose, galactose, mannose and N-acetylglucosamine. Amino-acid sequence analysis of six proteolytic peptides corresponded to sequences predicted by the cDNA. The molecular masses of the purified enzyme, estimated by electrospray mass spectroscopy and laser desorption time-of-flight analysis are 46.85 and 46.62 kDa, respectively, approx. 10% greater than the polypeptide portion predicted by the cDNA. The recombinant enzyme retains significant catalytic activity after modification with poly(ethylene glycol), a treatment which decreases the immunogenicity and increases the circulation life of many proteins used therapeutically.

Amidohydrolases↗
PubMed1994

Visceral pain threshold is deeply lowered far from the head in migraine.

A short-lasting over-distension of the hand-forearm veins, obtained through a non-invasive original maneuver (Hand Arm Vein Distension test) induces local pain when applied to migraine sufferers in inter-critical period. Conversely, subjects with an absolutely negative personal and family history for any type of idiopathic headache do not report any pain or only an uncertain, slight one. The injection of 1 mL of 2% to 8% (i.e. 0.34 mol/L to 1.36 mol/L) hypertonic saline into the antecubital vein during an extemporary short (1 minute) circulatory blockage (ischemia induced to guarantee a strictly local action of the chemical stimulus) provokes moderate, strong or unbearable local (arm vein) pain in migraine sufferers but not in subjects with a personal and family history absolutely free from any type of headache. These results show for the first time that migraineurs show a proneness to visceral pain in viscera (veins) distant from the head (arm-hand). Such a finding is consistent with the theory that migraine pain is due to a central derangement of the viscerosensory system.

Adult↗
PubMed1992

Multiple transcripts encoded by the ilvGMEDA gene cluster of Escherichia coli K-12.

We report here that, using Northern (RNA) blots, we identified two relatively stable transcripts of 4.6 and 1.1 kb that correspond to the products of the ilvEDA and ilvE genes and two relatively unstable transcripts of 6.7 and 3.6 kb that correspond to the products of the ilvGMEDA and ilvDA genes. The transcripts were identified by the use of eight probes derived from segments of the ilvGMEDA cluster. In addition, we used two strains with deletions of ilvG or ilvDA and observed the expected decrease in transcript size in Northern blots. Primer extension with reverse transcriptase generated a 169-nucleotide product corresponding to a 5' end within the ilvED intercistronic region, 37 nucleotides from the AUG codon of the ilvD gene. This primer extension product presumably indicates the 5' end of the ilvDA transcript that we detected in Northern blots. The stability of the transcripts was monitored, and RNase E was found to play a major role in ilv transcript degradation. Transcript levels varied in response to growth in the presence of the end product amino acids and in response to the presence of the polar frameshift site in ilvG. Although there have been speculations about the identities and numbers of transcripts derived from the ilvGMEDA cluster on the basis of the identification of some of the sites of transcription initiation and termination, this is the first report of the use of Northern blots to determine the actual sizes and distribution of mRNAs present in vivo.

Escherichia coli↗
PubMed1991

Sequence and transcriptional activity of the Escherichia coli K-12 chromosome region between rrnC and ilvGMEDA.

We previously identified a protein related to the expression of the ilvGMEDA cluster of Escherichia coli K-12. It was observed that this ilv-related protein was produced at higher levels in UV irradiated cells infected with lambda dilvGMEDA phage with specific ilvG mutations (ValR), compared to phage carrying the wild-type(ValS) ilvG allele. The gene encoding this protein was further localized to a region between rrnC and ilvGMEDA by analyzing restriction fragment subsets in maxicells. We have now determined the nucleotide (nt) sequence of the 3.5-kb segment between rrnC and ilvGMEDA, and two open reading frames (ORFs) are present in the region expected to contain the ilv-related gene. These ORFs predicts Mrs of 18,751 (ORFI) and 20,085 (ORFII) Da, and both ORFs have a strong probability to encode proteins based on codon frequency analysis. Maxicell analysis revealed that a 1319-bp HindIII-SmaI fragment containing ORFI encodes the ilv-related peptide. We deleted a ClaI fragment that removed a portion of ORFI encoding the C-terminal region of the peptide, and maxicell analysis revealed a decrease in the size of the protein produced in accord with the prediction. RNA slot blots and Northern blots were used to characterize transcripts encoding ORFI. A transcript initiated 112 nt from the ilvGp2 promoter, but proceeding in the opposite direction, may encode the ORFI peptide.

Amino Acid Sequence↗
PubMed1991

Low doses of TRH in amyotrophic lateral sclerosis and in other neurological diseases.

30 subjects--23 with amyotrophic lateral sclerosis (ALS), 4 with Charcot-Marie Tooth atrophy, 2 with progressive spinal muscle atrophy and 1 with radiation myelopathy--were given chronic low-dose TRH therapy. The effects of treatment were assessed on the scale of Norris et al. (1974). The outcome of the study, in agreement with some and at variance with other studies, was that TRH induced a statistically significant neurological improvement in 17 of the 23 ALS patients but little or none in the other ALS patients and in patients with other neurological diseases.

Adult↗
PubMed1991

Influence of the fluoride ion in the stability of bone hydroxyapatite achieved in patients after the fluo-calcic therapy.

It has been proposed that fluoride ion might actively enter into the basic structural framework of the bone, within its main constituent, the hydroxyapatite (HA), by substituting systematically the OH- ion in the crystal chemical formula Ca5[(PO4)3OH]. Accurate compositional studies have become necessary in order to explain an eventual stabilizing effect. Loss in weight (TG) and chemical reaction (DTG) while varying the temperature have been carried out for the first time on specimens under normal conditions and after fluo-calcic treatment, in parallel with accurate chemical compositional determinations by atomic absorption analysis. Our investigation shows that the new structure present after treatment is mechanically stable and proves more resistant to osteolytic processes.

Bone Neoplasms↗
PubMed1990

Interferon alpha-2a in cutaneous T-cell lymphoma.

23 newly diagnosed patients affected by cutaneous T-cell lymphoma were treated with sub-cutaneous interferon alpha-2a to evaluate the therapeutic efficacy and the toxicity of this agent. IFN was administered daily with dose escalation from 3 to 18 million units for 12 weeks; thereafter, patients induced into complete (CR) or partial (PR) remission were given IFN at maximal tolerated dose 3 times weekly for 6 or 9 months. The objective tumor response was observed in 17 patients (74%): 8 (35%) were CR and 9 (39%) were PR. A 74-yr-old patient died because of neutropenia and sepsis at the end of induction phase, while receiving IFN at dose of 18 million units. Disease stage is the initial feature predictive of response to IFN therapy. The dose schedule of this study was well tolerated: only 3 patients developed liver toxicity, while leukopenia was evident in 6 patients. Only 2 CR patients have relapsed, 18 and 24 months from response; the remaining 6 CR patients are in continuous complete remission with a median follow-up of 41.8 months. 6 PR patients have progressed from 8 to 17 months after response, and in the 3 PR patients not yet progressed the response duration ranges from 20 to 24 months. In conclusion, interferon alpha-2a is a very effective agent in therapy of untreated cutaneous T-cell lymphoma with an overall response rate of 74%.

Adult↗
PubMed1990

Membranous nephropathy associated with giant lymph node hyperplasia. A case report with histological and ultrastructural studies.

A young woman presented with nephrotic syndrome due to membranous nephropathy and a localized form of giant lymph node hyperplasia (Castleman's disease) occurring as a large intra-abdominal mass. Five months after surgical removal of the mass, only mild proteinuria persisted. Twenty months later a second kidney biopsy showed a near-normal morphology. Six years later the patient was free of symptoms and had normal urinalysis. Reviewing the pertinent literature, it seems to be the first case of a biopsy-proven cure of membranous nephropathy in a patient with membranous nephropathy and Castleman's disease.

Adolescent↗
PubMed1990

[CT in the staging of neoplasms of the gallbladder].

The authors report the results of 50 cases of gallbladder carcinoma studied by means of CT, which were observed since 1984. Twenty-five cases were confirmed at surgery and 25 were selected among those in which CT, clinical history, natural disease evolution and matching with other instrumental and laboratory examinations were highly suggestive of gallbladder carcinoma. The high incidence is reported of such CT signs, which may be considered typical, as the presence of soft tissue in gallbladder area (92%), liver infiltration (78%), and the presence of metastatic lymph nodes (36%); they may or may not be associated to less specific signs. CT appears as the most reliable examination for both diagnosis and staging of the disease. Unfortunately, due to the wide range of aspecific clinical signs, diagnosis is in most cases late and the disease has therefore a fatal outcome.

Adult↗
PubMed1989

High-performance liquid chromatography of amino acids, peptides and proteins. XCIII. Comparison of methods for the purification of mouse monoclonal immunoglobulin M autoantibodies.

A comparison of methods for the purification of naturally occurring mouse monoclonal autoantibodies, of the immunoglobulin M (IgM) isotype, has been performed to determine the optimal strategies for the isolation of IgM from ascites fluid and in vitro tissue culture hybridoma supernatants. In order to quantify each purification procedure, the concentration of IgM in eluted fractions was determined by using a double-sandwich mu-chain-specific anti-IgM enzyme-linked immunosorbent assay, and the purity of the IgM was determined by a bicinchoninic acid-based protein assay and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The most efficient single-step purification was based on size-exclusion chromatography on high-resolution Superose 6 HR 10/30 fast protein liquid chromatography (FPLC) columns. This procedure resulted in recoveries of monoclonal IgMs of ca. 71-86% with purities between 68 and 86%. Single-step chromatography of monoclonal IgM, on Superose 6 FPLC columns resulted in a 21-fold purification of IgM, prepared by the in vitro culture of hybridoma cells in dialysis membrane. Size-exclusion chromatography, performed with Sephacryl S-300 columns, resulted in reduced resolution of monoclonal IgM, with yields of ca. 57-80% and purity of ca. 42-58% compared with the high-resolution Superose 6 FPLC columns. "Non-ideal" size-exclusion chromatography on Superose 6 FPLC columns resulted in selective retention of monoclonal IgMs and elution of IgM with high-ionic-strength buffers in the trailing peak. Recovery of IgM with this strategy was high (ca. 82-92%) but the purity was not comparable to the single-step fractionation of IgM on Superose 6 FPLC columns. Single-step anion- and cation-exchange and mixed-mode hydroxyapatite chromatography resulted in only partial purification of monoclonal IgM with the applied procedures. With these latter separation techniques, monoclonal IgM was eluted with a variety of other ascites fluid or supernatant proteins, including those with apparent molecular weights identical to those of mouse IgG and albumin. Sequential purification of monoclonal IgMs by Mono Q anion exchange, followed by Superose 6 FPLC columns, resulted in a 2- to 3-fold purification of IgM but did not separate IgM from high-molecular-weight contaminants with apparent molecular weights similar to those of alpha 2-macroglobulin and IgG. Enrichment of monoclonal IgM from ascites fluid by ammonium sulphate precipitation revealed increasing IgM recovery with increasing ammonium sulphate final concentrations up to 60%.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1989

Biological osteosynthesis in osteochondral lesions of the talus.

Osteochondral lesions of the dome of the talus whether medial or lateral are rare. Surgical treatment is required when there is a loose body, or when the lesion is symptomatic and resistant to nonsurgical treatment. Usually, the degenerated fragment is removed, followed by curettage and multiple perforations of the subchondral bed, but different methods may be used to reinsert the osteocartilaginous fragment. Having been satisfied with our first studies conducted both on animals and man, we began to reinsert the osteochondral fragment by using resorbable means of synthesis. The purpose of this study is to report our experiences with 3 such cases at a minimum follow-up of one year.

Adolescent↗
PubMed1986

Characterization of vaccinia virus transcripts involved in selective inhibition of host protein synthesis.

Vaccinia virus transcripts synthesized in vitro inhibit protein synthesis directed by globin mRNA, EMC RNA, and total cytoplasmic RNA isolated from HeLa and CHO cells in micrococcal nuclease-treated reticulocyte lysates. In contrast, RNA isolated from vaccinia virus-infected cells is efficiently translated in the same system in the presence of the in vitro transcripts (G. Coppola and R. Bablanian (1983), Proc. Natl. Acad. Sci. USA 80, 75-79). In this study, we have fractionated the in vitro transcripts by acid-urea-agarose gel electrophoresis and demonstrated that the smallest RNA fraction inhibited translation of HeLa cell mRNA in vitro but had no effect on vaccinia virus mRNA translation. On the other hand, the larger RNA species inhibited nonselectively. These results indicate that the selective inhibitory activity of vaccinia virus transcripts resides only in the small poly(A)-containing in vitro RNA fraction.

Binding, Competitive↗