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Biomedical subjects

E May

Publications and source records attributed to E May.

At least 73 records · Page 4Linked to original sources
PubMed1993

Enoximone therapy as pharmacological bridging to cardiac transplantation.

Keeping pre-transplant patients alive while waiting for a suitable donor is still a major challenge. New pharmacological agents which can provide improved hemodynamics are urgently needed in patients with severe heart failure who are on the waiting list for cardiac transplantation. Intravenous enoximone therapy (an initial 0.5 mg/kg bolus, then 1.25-5.0 mcg/kg/min infusion) was administered to 35 transplant candidates with progressive heart failure despite optimal drug regimen including digoxin, diuretics, and ACE-inhibitors. In 18 out of 35 patients complete hemodynamic, echocardiographic, neurohumoral, and Holter-ECG studies were performed before and 24 hours after intravenous enoximone infusion. Patients were then continued on chronic oral therapy of 100 mg twice a day. Enoximone infusion increased the cardiac index (CI) (1.78 +/- 0.45 l/min/m2 vs 3.04 +/- 0.83 l/min/m2; p < 0.001) and stroke volume index (SVI)(22.33 +/- 9.45 ml/m2 vs 32.28 +/- 7.29 ml/m2; p < 0.05) and decreased wedge pressure (PCP)(24.1 +/- 11.98 mmHg vs 17.78 +/- 8.76 mmHg; p < 0.05) while mean arterial pressure (MAP) was unchanged. Left ventricular ejection time (LVET)(225.1 +/- 26.9 ms vs 242.2 +/- 25.8 ms; p < 0.05) was increased whereas other echocardiographic parameters were unchanged (Left ventricular end-diastolic dimension LVEDD, left ventricular end-systolic dimension LVESD, fractional shortening FS, early diastolic relaxation parameter Te). Plasma neurohumoral parameters did not change (Aldosterone, epinephrine, renin, atrial natriuretic factor) except for a significant drop in norepinephrine (936.7 +/- 443.2 pg/ml vs 522.4 +/- 287.6 pg/ml; p < 0.05). Holter-ECG parameters (ventricular premature beats VPB, couplets, ventricular tachycardia VT) were not influenced by enoximone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Transforming growth factor-alpha: characterization of the BamHI, RsaI, and TaqI polymorphic regions.

We have characterized the nature of structural alleles of the transforming growth factor-alpha (TGF alpha) locus by restriction-enzyme digestion with BamHI, RsaI, and TaqI. The BamHI polymorphic site is located within exon VI, which codes for the 3' untranslated region. The two BamHI alleles differ by a single point mutation at the restriction site. The RsaI and TaqI polymorphic sites are located within intron V. The two alleles differ at the restriction site, either by a point mutation (RsaI) or by a 4-bp deletion (TaqI). This analysis permits us to devise a PCR method coupled with restriction digestions to directly identify the TGF alpha polymorphisms. Analysis of 99 Caucasian controls has revealed a highly significant (P < .001) association between the RsaI and the BamHI genotype. The frequency of the rare BamHI allele was significantly higher (P < .001) in transformed cell lines (.30) than in controls (.076).

Alleles↗
PubMed1993

Analysis of the p53 gene in European hepatocellular carcinomas and hepatoblastomas.

Human hepatocellular carcinomas (HCC) and hepatoblastomas (HB) from patients in France and Italy, respectively, which are both areas with a low incidence of HCC and a low dietary exposure to aflatoxin B1 (AFB1), were analysed for alterations of the p53 tumour suppressor gene. An abnormality in the p53 gene was detected in only one of the seven HCCs examined. Sequencing of the cDNA of this HCC revealed a G to T transversion at the first nucleotide of codon 245 that was not found in normal tissue, excluding the possibility of germinal transmission of this alteration. All tumours had the wild-type sequence at codon 249, which has been reported to be a mutational hot spot in the p53 gene in HCCs from high incidence areas, such as China and Southern Africa. Seven samples of HB, the most common hepatic tumour of children, were also tested for loss of heterozygosity (LOH) and mutations in the p53 gene. In contrast to what is observed in HCC of adulthood, for which environmental conditions are important etiological risk factors, HB probably stems uniquely from genetic disorders. PCR-direct sequencing of exons 4 to 8 and PCR-single strand conformation polymorphism (PCRSSCP) of exons 2, 3 and 9 revealed no mutations in the coding sequences examined. LOH was observed in one of the five informative cases when codon 72 and intron 6 were subjected to polymorphism analysis.

Adult↗
PubMed1992

Simian virus 40 T antigen activates the late promoter by modulating the activity of negative regulatory elements.

Late promoter activity measured before viral DNA replication results from a complex involvement of negative and positive cis-acting elements located both in the enhancer and in the 21-bp repeats. GC motifs located within the 21-bp repeats act in cooperation with sequences overlapping the early TATA box to down-regulate the late promoter activity. Analysis of insertion mutants indicates that the late promoter might be negatively regulated at least partially by the early promoter machinery. The GTI motif located within the enhancer as well as the GC motifs lose the ability to down-regulate the late promoter in the presence of T antigen. Results obtained with tsA58 protein indicate that two different domains of T antigen are involved in the negative autoregulation of the early promoter activity and in the release of the down-regulation of the late promoter by the GC motifs.

Animals↗
PubMed1992

p53 mutations in Raji cells: characterization and localization relative to other Burkitt's lymphomas.

The nuclear phosphoprotein p53 is an important regulator of cell proliferation in normal cells. Interestingly, the gene encoding p53 has usually undergone mutations in a wide range of tumor types. Recent studies of the p53 gene in Burkitt's lymphomas have demonstrated that mutations are extremely common, and in fact it is rare that both alleles of the p53 gene in these tumors are not inactivated by mutation or deletion. We present here genetic data regarding the status of the p53 gene in the Burkitt lymphoma cell line, Raji. As is typical for this type of tumor, both alleles have undergone point mutations. Further, statistical analysis of available data from a large number of Burkitt's lymphomas indicates an apparent tumor-specific distribution of p53 mutations. The possibility that specific mutations of the p53 gene may be important for different tumor types is discussed.

Alleles↗
PubMed1992

[The interpretation of morphometric data of 10- to 13-year-old school children from the survey year 1978 of the Braunschweig Longitudinal Study].

The paper represents a cross-sectional study from a sample of 1800 out of 3000 school-children from the Braunschweiger Längsschnitt. In this methodical approach we first eliminate approximately the influence of age and stature on the raw data from all body measurements with regression equations. The transformed data were attached to three "types" named 'below normal', 'normal', and 'above normal', in course of which 'normal' means all cases in the range of the standard deviation, whereas the two other "types" are corresponding to the adjacent ranges of values. Subsequently each transformation on the mean of age and stature a discriminant analysis has been performed grouping the cases by the "types" of the width of pelvis, resp. shoulders. There were found great influences of the stature on the chosen measures of width in our investigated class of age. They could be made clear alone by using allometrical methods. Only before correction of the body height the given grouping is supported by other variables, at which different sets of variables dominate the discriminant functions for boys and girls. Out of this new aspects and considerations result for the understanding of the physique and the physique typologies, which would be significant in our opinion for acceleration phenomenon as well as for the comparative examinations on populations.

Age Factors↗
PubMed1991

Immunological evidence for the association between simian virus 40 115-kDa super T antigen and hsp70 proteins in rat, monkey, and human cells.

Immunological evidence was provided that in subclone 7 cell line, which is derived from SV40 transformed cells, 115-kDa super T antigen, a transformation-competent, elongated form of large T antigen was physically complexed with hsp70 proteins. This conclusion was first based on the coimmunoprecipitation from unstressed or heat shocked subclone 7 cells of both super T antigen and hsp70 proteins. This was observed with any one of a set of anti-T monoclonal antibodies reacting to determinants located either in the C-terminal region or in the N terminal region. Reciprocally coimmunoprecipitation of both hsp70 and super T was also observed in the anti-hsp70 peptide serum-immunoprecipitate. The formation of complexes between hsp70 proteins and super T antigen in subclone 7 cells was also confirmed by Western blot experiments. Moreover, when expressed in cell lines originating from human (Hela cells) or monkey (CV1P cells) species following transfection with the relevant plasmid, super T antigen again displayed the ability to associate with hsp70 proteins. Considering that super T antigen was obtained in laboratory experiments as a stable evolutionary variant of SV40 large T antigen, it is suggested that the marked ability of super T antigen to associate with heat shock protein could be selectively advantageous under certain conditions.

Animals↗
PubMed1991

Characterization of SV40 enhancer motifs involved in positive and negative regulation of the constitutive late promoter activity; effect of T-antigen.

By analyzing the late promoter activity of a series of nonreplicative recombinants mutated within the different enhancer motifs of SV40 we identified both positive and negative regulatory elements. In the absence of T-antigen, the motifs Sph and/or octamer, and to a lesser extent the motifs GTI and P, account for the constitutive expression of the late promoter. The motif GTII overlaps elements that negatively regulate the expression of the late promoter. These results indicate that the late promoter is down-regulated not only at the level of the GC motifs but also at the enhancer level. Moreover, we showed that T-antigen interacts with both positive and negative regulatory elements.

Antigens, Viral, Tumor↗
PubMed1991

Angiofollicular lymph node hyperplasia and peripheral neuropathy. Case report and literature review.

A man with multicentric angiofollicular lymph node hyperplasia and a polyclonal gammopathy developed a debilitating sensory-motor peripheral neuropathy that resolved with plasma-pheresis and immunosuppressive therapy. Fourteen similar cases have been reported in the literature; however, to our knowledge, this is the first report of successful treatment with plasma-pheresis. Severe peripheral neuropathy usually occurs in the setting of multicentric, plasma cell-type disease with hypergammaglobulinemia and is often responsive to immunosuppressive therapy.

Aged↗
PubMed1991

Endogenous HeLa p53 proteins are easily detected in HeLa cells transfected with mouse deletion mutant p53 gene.

It has been reported [Matlashewski et al. (1986). Eur. J. Biochem., 154, 665-672] that HeLa cells contain no detectable p53 protein, although they contain p53 mRNA which is translationally active. Here it is shown that endogenous HeLa p53 proteins were easily detected in HeLa cells transiently expressing mouse deletion mutant p53 gene after transfection with the appropriate recombinant plasmid. This detection was obtained by immunoprecipitation coupled with SDS-PAGE as well as by Western blotting experiments. Our results strongly suggest that HeLa p53 mRNA is actually translated in vivo, generating an extremely unstable p53 protein. Considering that the HeLa cell line is a HPV-18-positive human cervical carcinoma cell line, this high instability of HeLa p53 proteins is in keeping with the finding that E6 oncoprotein encoded by human papillomavirus 16 or 18 promotes the degradation of p53 proteins [Scheffner et al. (1990). Cell, 63, 1129-1136].

Animals↗
PubMed1990

Human breast cancer: identification of populations with a high risk of early relapse in relation to both oestrogen receptor status and c-erbB-2 overexpression.

We recently defined a new early prognostic factor, the ER+(R) status, which permits the discrimination of a group presenting a high risk of early relapse among the ER+ patients. This group was referred to as ER+(R2) in contrast to ER+(R1) which corresponded to the group of ER+ patients having a lower risk of early relapse. Taking into account the whole population including the ER- and inflammatory tumours, we have extended this view and showed that ER+(R) status is a significant predictor of disease-free survival. Determination of c-erbB-2 mRNA levels in the same series of tumours showed that high expression of c-erbB-2 mRNA is significantly correlated with ER-, inflammatory tumours and with lymph nodes involvement. Moreover, a multivariate analysis showed that c-erbB-2 mRNA overexpression was a significant predictor of early relapse (P = 0.02), as significant as ER negativity and ER+(R2). For ER+ patients a high level of c-erbB-2 mRNA constitutes a higher risk of relapse for both ER+(R1) and ER+(R2) patients. However, in the case of ER- patients, early relapses were strongly correlated with c-erbB-2 overexpression. The counterpart of this observation is that ER- patients with no overexpression of c-erbB-2 constitute a group with a relatively good prognosis.

Age Factors↗
PubMed1990

[Central hemodynamics of a new positive inotropic substance, adibendan. Data from a dose-finding study].

Central Hemodynamics from the New Positive-inotrope Substance Adibendan/An open dose-finding study We investigated the influence of Adibendan which is a new phophodiesterase inhibitor on central hemodynamics in an open dose-finding study. 10 patients with chronic heart failure NYHA II-IV (mean age 67 +/- 5 years) got Adibendan i.v. A maximum increase in cardiac index from 2.3 +/- 0.5 to 3.2 +/- 0.5 l/min.m2 (p less than 0.001) was seen after a cumulative dosage of 0.916 +/- 0.571 mg at a time interval of 107 +/- 43 min after injection of the first dosage of 0.125 mg. There was a pronounced increase in stroke volume index from 30 +/- 6 to 40 +/- 8 ml/m2 (p less than 0.01). Heart rate raised by 5% which was not significant. Systemic vascular resistance dropped by 30% from 1693 +/- 720 to 1177 +/- 292 dyn.s.cm-5 (p less than 0.05), pulmonary vascular resistance by 39% from 755 +/- 273 to 463 +/- 199 dyn.s.cm-5 (p less than 0.001). Blood pressure and right atrial pressure did not alter. Mean pulmonary artery pressure dropped by 14% from 37 +/- 7 to 32 +/- 11 mmHg. We conclude that Adibendan improves cardiac index markedly and causes a modest decrease in mean pulmonary artery pressure.

Aged↗