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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 865 records · Page 48Linked to original sources

Sequencing the erbA gene of avian erythroblastosis virus reveals a new type of oncogene.

Avian erythroblastosis virus (AEV) contains two distinct oncogenes, erbA and erbB . The erbB oncogene, which is homologous to a portion of the epidermal growth factor receptor, is related to the src family of oncogenes and efficiently transforms erythroblasts, whereas erbA potentiates the effects of erbB by blocking the differentiation of erythroblasts at an immature stage. This "potentiator" was sequenced; the amino acid sequence deduced from it was clearly different from the sequences of other known oncogene products and was related to carbonic anhydrases. These enzymes participate in the transport of carbon dioxide by erythrocytes, the precursors of which are main targets of avian erythroblastosis virus. A src-related oncogene such as erbB in synergy with an activated specific cell-derived gene such as erbA can profoundly affect early erythroid differentiation.

Alpharetrovirus↗

Structural changes of liver microsomes in rat during neonatal life: influence on the glucuronidation rates of various substrates.

The Vmax of the membrane bound UDP-glucuronosyltransferase (UDP-GT) towards group 1 substrates (4-nitrophenol, 2-naphthol) was particularly higher in young rats than in adults. On the contrary, activity towards group 2 substrates such as borneol or testosterone was not detectable in fetus liver. The developmental pattern of UDP-GT was related to changes in lipid composition of microsomes, namely in the content in lysophosphatidylcholine which rose at birth. The phospholipid-cholesterol molar ratio also increased 2 fold from the 16th day of fetal life to the 4th day after birth. Measurement of the steady state anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) as well as determination of the order parameter S and the rotation cone angle of the fluorescent probe strongly suggested an increase in membrane fluidity in rat liver microsomes during ontogenesis.

Animals↗

Nucleotide sequence of the human c-myc locus: provocative open reading frame within the first exon.

The nucleotide sequence of a HindIII-EcoRI DNA fragment, 8 kbp long, of a lambda recombinant containing the whole human c-myc gene has been deduced by the method of Maxam and Gilbert. This fragment encodes the complex c-myc locus and the sequence provides information relative to the 2.7 kb long c-myc transcript. It appears that although exons 2 and 3 would code for a 48-K protein homologous to the myc domain of the viral p110 gag-myc protein, the first exon, which has a large open reading frame ending with a stop codon just upstream from the donor splice site, could code on its own for a 20-K protein. Speculations about the role of that putative protein on the regulation of the expression of exons 2 and 3 are made.

Base Sequence↗

Fractionation of the multiple forms of bovine gastric aspartic proteases by chromatofocusing.

By extending the chromatofocusing technique to a very acidic pH range (down to pH 2.0) a method which, in a single-step procedure, allows separation of the three main aspartic proteases secreted by the bovine abomasal mucosa i.e., chymosin (EC 3.4.23.4), gastricsin (EC 3.4.23.3), and pepsin A (EC 3.4.23.1), has been developed. Starting materials for separation were crude commercial milk-clotting extracts or abomasal juices. A multistep procedure, using narrower pH gradients, enabled the fractionation of these proteases into their multiple forms. Chymosins A and B, which are known to differ only by a single amino acid substitution (Asp/Gly), were completely resolved. Their elution pHs, 3.75 and 3.80, respectively, though far from their "normal" pIs (around 4.7 in isoelectric focusing), demonstrate the resolving power of such a technique. Multiple forms of bovine pepsin A, which differ in their organic phosphate content (0-3 phosphate group(s) per molecule of enzyme) and whose pIs are lower than 2.5, were also separated using 15-20 mM glycine buffer, pH 2.0, as eluent. Although many attempts to get a linear gradient remained unsuccessful within this pH range, resolution appeared quite satisfactory, as judged from analytical isoelectric focusing patterns. In particular, the two subcomponents of bpA1, which presumably have a different site of post-translational phosphorylation, were resolved in this way.

Abomasum↗

Increased transcription of the c-myc oncogene in two methylcholanthrene-induced quail fibroblastic cell lines.

The expression of three c-onc genes (c-erb, c-myc, c-myb) was investigated in five cell lines established from fibrosarcomas induced with 20-methylcholanthrene (MCA) of Japanese quails. These cell lines showed low levels of the three c-onc genes, with the exception of two cell lines that accumulated moderate (MCAQ 1-4) and large amounts (MCAQ3-5) of c-myc RNA. Molecular cloning and restriction endonuclease analyses indicated that expression of c-myc in these two cell lines were not associated with detectable rearrangements in the c-myc locus, that the size of the c-myc transcript (2.7 kb) in MCAQ 3-5 was similar to that of the normal c-myc messenger RNAs (mRNA) and that the transcriptional activation observed in MCAQ 3-5 was not mediated by the LTR (long terminal repeat) of a proximate ALV (avian leukosis virus) provirus. Finally, when analysed with the restriction enzymes Msp I and Hpa II, the c-myc locus of MCAQ 3-5 and MCAQ 1-4 was found hypomethylated as compared with that of the other cell lines tested that show low levels of c-myc transcripts. Our results suggest that one of the ways methylcholantrene could mediate transformation is by inducing an abnormal regulation of the c-myc gene.

Animals↗

Chromosomes in human large bowel tumors. A study of chromosome #1.

Chromosome studies on 49 patients with large bowel adenocarcinomas showed abnormalities of chromosome #1 in 19 cases (39%). One had monosomy, 13 showed trisomy, and 5 cases had structural abnormalities. Eighteen patients had tumors on the right side of the colon; of these, only 3 had an abnormal #1 (17%); 16 of 28 tumors (57%) located on the left side had abnormalities of #1. The regions of consistent duplication of 1q were q24----q44? The presence or absence of changes of chromosome #1 may be useful as a prognostic indicator in large bowel cancer.

Adenocarcinoma↗

[Effect of the degree of phosphorylation of bovine pepsin A on its enzymatic activity].

Proteolytic and clotting activities of bovine pepsin A with respect to its degree of phosphorylation were studied on various substrates. The occurrence of phosphate group(s) on bovine pepsin A more or less strongly affects its enzymic properties according to the substrate and its environment. This is particularly obvious as far as kappa-casein is concerned. The specific flocculating activity of unphosphorylated (fA0) as well as dephosphorylated (treated with potato acid phosphatase) bovine pepsin A, determined on a 0.2% kappa-casein solution, is significantly higher than that observed with phosphorylated pepsins, especially after kappa-casein was treated with alpha-D.N-acetyl galactosaminyl oligosaccharidase, while specific milk clotting activity remains unchanged regardless to the level of phosphorylation of bovine pepsin A is. Using haemoglobin as substrate, unphosphorylated pepsin A exhibits the highest specific proteolytic activity and the less acidic pH optimum. Conversely, the amount of phosphate groups does not seem to have any effect on the peptidase activity assayed towards the synthetic chromophoric hexapeptide Leu-Ser-Phe(NO2)-Nle-Ala-Leu-OMe. By treating whole bovine pepsin A with potato acid phosphatase during 24 h at 37 degrees C and pH 5.6, using a 1/100 E/S ratio, almost complete dephosphorylation can be reached. The stability of different bovine pepsin A preparations, more or less phosphorylated, treated or not with phosphatase was also investigated. At pH 2.2, phosphorylated bovine pepsin A is twice more stable at 37 degrees C than the dephosphorylated enzymes while dephosphorylated pepsin does not exhibit any degradation at pH 5.6, judging by isoelectric focusing patterns, or loss of activity. Such a result suggests that post-translational phosphorylation might play an essential physiological function by improving the stability and integrity of pepsin in the bovine abomasum, the pH of which is very acidic (between 1.0 and 2.0).

Animals↗

Aberrent group B reactions detected in mixtures of semen and vaginal secretions possibly due to acquired B.

Routine ABO grouping tests performed on vaginal swabs from a group O female showed the presence of blood group B activity as well as the expected A and H activity after intercourse with her group A partner. The source of the B activity was readily detectable using the Laboratory's routine elution test, but it was not detectable when a monoclonal anti-B was used and detection by the inhibition technique was possible only with a selected antiserum. A possible explanation of the reactions observed is that the acquired B is capable of reacting with only a portion of the antibodies present in normal polyclonal anti-B sera.

ABO Blood-Group System↗

[Twin pregnancy--a special problem of modern obstetric medicine].

Basing on an exemplary organized health protection incorporating up-to-date technique, progressive management of delivery and optimal neonatal care, we were able to reduce the perinatal mortality of all pairs of twins at the UFK Jena in the periods between 1977/79 (n = 204) and 1980/82 (n = 174) from 8,33% to 3,30%. The difference was statistically significant (p less than 0.05). The late morbidity of these children also showed a statistically significant decline (p less than 0.05).

Apgar Score↗

Effect of whole body hyperthermia and BCNU on the development of radiation myelitis in the rat.

A radiant heat device was used to study the interaction of 41.8 degrees C whole body hyperthermia (WBH), radiation (40 Gy) and the lipophilic anti-neoplastic agent BCNU in the development of myelitis in the rat spinal cord. The addition of WBH and BCNU neither precipitated myelitis acutely nor shortened the latency before the onset of neurological signs in irradiated animals.

Animals↗

HLA DR4 and giant cell arteritis.

We reported the data of HLA-DR frequencies in a new series of 40 unrelated patients suffering from giant cells arteritis (Horton's disease). As previously reported by us, a large increase of HLA-DR4 antigen frequency is noted in patients compared with 146 healthy controls. Moreover, gathering together these 40 patients with the 48 other patients of our first published data, increase of the DR4 frequency is largely confirmed with a Pc less than 0.001.

Arteritis↗

Observations on the distinction between oligotrophic and eutrophic marine bacteria.

The nutritional requirements of two marine bacteria designated as oligotrophic because they could grow on media containing 10 mg of C per liter supplied as peptone and two classified as eutrophic because they could grow only at higher concentrations of C supplied as peptone were examined. Each of the four organisms was found to have its own unique group of compounds which could serve either individually or in combination as sources of carbon and energy for growth. When the peptone in the medium was replaced by another appropriate source of carbon and energy, the difference in the capacity of the organisms examined to grow at 10 mg of C per liter disappeared, and all four organisms could be described as being oligotrophic. Some of the organisms required a low concentration of one specific carbon source but a higher concentration of another. One of the organisms was inhibited by high concentrations of one specific carbon source but not by another. The observations indicate that current methods of enumeration based on the capacity of cells to grow in the presence of high or low concentrations of complex mixtures of nutrients such as peptone do not distinguish between two broad classes of bacteria differing intrinsically in their ability to grow at high and low concentrations of nutrients. Whether two such broad classes exist seems extremely doubtful. Which organisms will multiply in a particular environment will depend on both the specific nutrients available and their concentrations.

Journal Article↗

Fade of the responses of the isolated, blood-perfused dog atrium to cholinergic interventions.

In the isolated, blood-perfused, canine right atrium, intramural parasympathetic nerve stimulation and intra-arterial infusions of acetylcholine induced substantial negative chronotropic and inotropic responses. The responses to parasympathetic stimulation reached their maximum values quickly, and then usually faded back toward control levels over the next 1 or 2 min of stimulation. The fade of the responses at high stimulation frequencies (greater than or equal to 30 Hz) was significantly greater than that at lower frequencies. The inotropic responses to acetylcholine infusion (1 microgram/min) faded slightly but significantly, whereas the chronotropic responses did not fade at all. These results suggest that the fade of the cardiac responses to parasympathetic stimulation is mainly ascribable to a progressive reduction in the rate of acetylcholine release from the nerve endings, especially at higher stimulation frequencies. The fade of the inotropic responses was more pronounced and had a longer time course than that of the chronotropic responses. Furthermore, the fade of the inotropic responses diminished significantly as the response magnitude was augmented by an increase in stimulation voltage. Conversely, the fade of chronotropic responses was not significantly affected by this intervention. These differences in the inotropic and chronotropic responses to neural stimulation, and the occurrence of a slight fade of the inotropic response to acetylcholine infusion, suggest that in addition to the predominant prejunctional mechanism, a postjunctional phenomenon may also be partly responsible for the fade of the inotropic response to cholinergic interventions.

Acetylcholine↗

The effects of non-prescribing of anxiolytics in general practice. II. Factors associated with outcome.

Factors associated with psychiatric outcome were examined in a series of 87 patients who had presented in general practice with new episodes of minor affective disorder. Two outcome measures were used: (i) Status on Present State Examination (PSE) seven months after initial consultation; (ii) prescribing of psychotropic medication between one-month and seven-month follow-up assessments. Outcome according to the PSE was significantly associated with: worse measures of psychiatric state (General Health Questionnaire, Profile of Mood states) and of social functioning (SAS-M) at initial consultation and one month later; and with persistent anxious or depressed mood during the follow-up period; but not with life events. During the follow-up period 20 patients received at least one psychotropic prescription; they were significantly associated with worse initial GHQ scores, consumption of tobacco and non-prescribed medication, and initial anxiety. A sub-group of 11 patients received multiple psychotropic prescriptions; they were significantly associated with the same initial measures, and also with poor outcome measures (psychiatric and social).

Adult↗

Secondary malignancies after marrow transplantation.

Secondary malignancies after marrow transplantation have been observed in 20 patients: 19 patients underwent marrow transplantation for the treatment of a hemopoietic malignancy and one for aplastic anemia. All but three were given total body irradiation at doses of 8.0-15.75 Gy as part of the conditioning regimen. Secondary malignancies were composed of three groups: (a) Six patients had recurrence of leukemia (three acute lymphoblastic, two acute myeloblastic, and one chronic myelocytic) in cells of donor origin 62-1074 days after grafting. (b) Eight patients developed lymphoproliferative disorders (four of immunoblastic sarcoma type, one lymphoblastic, one follicular center cell, and one Hodgkin's lymphoma and one acute lymphoblastic leukemia) 54-730 days after grafting. In four of seven patients with appropriate studies these tumors were of donor-cell origin and in three of four tested the cells contained Epstein-Barr virus genome or expressed viral antigens. (c) Six patients developed solid tumors (two glioblastoma multiforme, two adenocarcinomas, one squamous cell carcinoma, and one sarcoma) 347-1875 days after grafting. All but two patients (one with glioblastoma and one with squamous cell carcinoma) have died. These data suggest that patients undergoing marrow transplantation for a hemopoietic malignancy may be at risk of developing secondary malignancies. The etiology appears to be multifactorial, including irradiation, immunosuppression, Epstein-Barr virus infections, and other factors.

Adolescent↗