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Biomedical subjects

G Petersen

Publications and source records attributed to G Petersen.

At least 55 records · Page 3Linked to original sources
PubMed1995

A Drosophila male accessory gland protein that is a member of the serpin superfamily of proteinase inhibitors is transferred to females during mating.

Accessory gland peptide 76A, (Acp76A), belongs to the serpin superfamily of proteins (serine protease inhibitors). Acp76A is a secreted protein synthesized only in the Drosophila melanogaster adult male accessory gland. Accumulation of the protein in males is first detected with polyclonal antibodies at 1 day after eclosion. The level of the protein in virgin males reaches a peak 5-8 days post-eclosion, and remains constant for at least 20 days. Upon mating the amount of Acp76A in males drops dramatically, but recovers by 24 h after mating. Immediately after mating the Acp76A is found in the female uterus. By 6 h after mating the amount of Acp76A detected in females is drastically reduced.

Animals↗
PubMed1994

The gene upstream of DmRP128 codes for a novel GTP-binding protein of Drosophila melanogaster.

Upstream of the gene coding for the second-largest subunit of RNA polymerase III (DmRP128) we have found another gene (128up), which is transcribed in the same direction as the RNA polymerase gene. The intergenic distance between the 3' end of 128up mRNA and the 5' end of DmRP128 mRNA is only about 100 bp. Transcripts of 128up are present at a much higher level than DmRP128 RNA in Drosophila Schneider 2 cells, embryos, and adult flies. Two transcription start points, seven nucleotides apart, are found for 128up compared to multiple scattered starts for DmRP128. Sequence analysis of 128up cDNA reveals that the gene codes for a 41 kDa protein with homology to GTP-binding proteins and matching four of the structural sequence motifs characteristic of the superfamily of GTPases. Bacterially expressed 128up protein fused to maltose-binding protein specifically binds GTP. Sequences closely related to the 128up protein are found in species as distant as Halobacterium, yeast or mouse; the murine protein is 80% identical to 128up. This evolutionary conservation is indicative of an important, but as yet unknown, physiological role. In accordance with the sequence conservation, antibodies against 128up specifically cross-react with mouse 3T3 cells and human Hep2 cells where the subcellular localization of the protein is predominantly perinuclear. We propose that 128up is a member of a novel class of GTP-binding proteins.

Amino Acid Sequence↗
PubMed1994

Cigarette smoking and drinking of alcohol are not associated with rapid progression to acquired immunodeficiency syndrome among homosexual men in Norway.

In order to study the influence of cigarette smoking and drinking of alcohol on the progression to acquired immunodeficiency syndrome (AIDS), eighty HIV infected homosexual men were included in a prospective study from the date of diagnosed HIV seropositivity. Two men were lost to follow-up. The mean follow-up time was 62 months. By the end of the follow-up period 26 out of 78 subjects (33%) were diagnosed with AIDS. When controlling for age, year of HIV diagnosis, number of male lifetime partners and frequency of receptive anal intercourse, the adjusted relative risk of being diagnosed with AIDS for the group smoking 1-20 cigarettes daily was 0.4 (0.2-1.2, 95% confidence interval) and 1.1 (0.4-2.7, 95% confidence interval) for the group smoking more than 20 cigarettes daily, as opposed to the non-smoking group. The adjusted relative risk of progression to AIDS for daily alcohol drinkers as opposed to less frequent drinkers was 0.8 (0.3-2.2, 95% confidence interval). The adjusted relative risks of receptive anal intercourse often or usually and more than 500 lifetime male partners were 2.2 and 2.0, respectively. These estimates, however, were not significantly above 1.0. The lack of positive association between cigarette smoking, drinking of alcohol and progression to AIDS found in this study as well as in other studies, may have implication for the understanding of the pathogenesis of the HIV disease and for counselling HIV infected subjects.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Bioequivalence of two commercially available levothyroxine-Na preparations in athyreotic patients.

The thyroid hormones levothyroxine and levotriiodothyronine are vital for normal growth and development and play an important role in energy metabolism. The bioequivalence of levothyroxine following administration of the test preparation (Eferox 100 tablets, Wyeth Pharma GmbH, Münster, Germany) and a reference preparation (each containing 100 micrograms levothyroxine-Na, the sodium salt of the natural thyroxine isomer) was investigated in 24 male and female patients with a lack of basal thyroid hormone secretion after an ablative thyroidectomy and postoperative radiotherapy. In a randomized, multicentric, open 3-factorial Latin-square (2 x 2 x 2) crossover study the subjects received two pharmaceutical units of the formulations once daily in the morning 30 min before breakfast during two periods of 35-42 consecutive days each. Serum concentrations of total thyroxine and total triiodothyronine were determined on screening day (basal concentrations), on the last 3 days of administration at predose to verify steady-state conditions, and on the last day of administration at 9 predetermined time points up to 24 h postadministration to obtain 24-h hormone profiles. The two formulations proved to be bioequivalent for levothyroxine regarding rate and extent of absorption. The bioequivalence decision was based on CSS,max and AUD0-24h.

Adult↗
PubMed1993

RPII15 codes for the M(r) 15,000 subunit 9 of Drosophila melanogaster RNA polymerase II.

The RPII15 gene product of Drosophila melanogaster, which has recently been identified by sequence comparison, possesses a high similarity to subunit 9 of yeast RNA polymerase II. Using the polymerase chain reaction the coding region of RPII15 was isolated from genomic DNA of adult flies. Sequence analysis shows four amino acid substitutions in comparison to the previously reported sequence. Antisera were generated against bacterially expressed RPII15 and were used for immunoblotting experiments with RNA polymerase II of Drosophila melanogaster. This analysis identified the M(r) 15,000 subunit 9 as gene product of RPII15.

Amino Acid Sequence↗
PubMed1993

[Pantothenic acid levels in blood of athletes at rest and after aerobic exercise].

Ninety-six high-performance athletes of various disciplines were available for this investigation. All athletes had many years of training and competition experience. The pantothenic acid contents in the blood were determined by means of microbiological measurements. In addition to the pantothenic acid level at rest, measurements were made resp. physical exertion in 14 marathon runners and nine body builders. Blood was collected for determination of pantothenic acid before (a), after (b) and 2 h after exercise. Compared to the reference values for untrained persons (1.34 +/- 0.13 nmol/mL), the marathon runners with 0.76 (0.31-0.94) nmol/mL and soccer players with 1.19 (0.37-2.64) nmol/mL were below the reference values. According to relative frequencies, more than 30% of all athletes were below the lower limit (< 1.20 nmol/mL). The values in body builders/racing cyclists differed significantly from those in marathon racers (p < 0.001), which is presumably due to unallowed supplementation. During exercise, there was a significant increase in the pantothenic acid level in marathon runners (p < 0.01).

Adult↗
PubMed1992

Molecular characterization of a putative peroxidase gene of Drosophila melanogaster.

We have identified genomic clones and corresponding cDNAs that encode a putative peroxidase of Drosophila melanogaster. The gene (DmPO) appears as a single copy gene located on the third chromosome at position 89 D/E. It is interrupted by seven small introns and one unusually large 5' intron (about 11 kb). Sequence analysis of the cDNA showed an open reading frame of 690 amino acids resulting in a protein of 77 kDa. The deduced amino acid sequence reveals an overall homology to myeloeosinophil and thyroid peroxidase, a human superfamily of peroxidases.

Amino Acid Sequence↗
PubMed1992

Evidence that the MCC-APC gene region in 5q21 is not the site for susceptibility to hereditary nonpolyposis colorectal carcinoma.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common form of hereditary colon cancer. Autosomal dominant inheritance is evident from pedigrees but the genetic basis of the disorder is otherwise unknown. Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and APC was shown to be the gene predisposing to familial adenomatous polyposis. To determine if these genes also confer susceptibility to HNPCC we performed linkage analyses in nine affected families. The MCC-APC region could be formally excluded as the locus for HNPCC in seven families. In one family the results were suggestive of exclusion, although they were not conclusive. The remaining family was uninformative. We used two alternative definitions of affected status. Based on haplotypes for MCC and APC the added pairwise logarithm-of-odds score for all nine families was -22.57 at the recombination fraction of 0.00 using more stringent criteria for the HNPCC phenotype and -22.67 for less stringent criteria. In addition to blood DNA samples from living family members, DNA from formaldehyde-fixed archival pathology specimens from decreased individuals contributed to these linkage results.

Base Sequence↗
PubMed1992

Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients.

We searched for germ-line mutations of the APC gene in 79 unrelated patients with familial adenomatous polyposis using a ribonuclease protection analysis coupled with polymerase chain reaction amplifications of genomic DNA. Mutations were found in 53 patients (67%); 28 of the mutations were small deletions and 2 were 1- to 2-base-pair insertions; 19 were point mutations resulting in stop codons and only 4 were missense point mutations. Thus, 92% of the mutations were predicted to result in truncations of the APC protein. More than two-thirds (68%) of the mutations were clustered in the 5' half of the last exon, and nearly two-fifths of the total mutations occurred at one of five positions. This information has significant implications for understanding the role of APC mutation in inherited forms of colorectal neoplasia and for designing effective methods for genetic counseling and presymptomatic diagnosis.

Adenoma↗
PubMed1992

Hepatitis B antibodies in HIV-infected homosexual men are associated with more rapid progression to AIDS.

OBJECTIVE: To study the influence of previous or present hepatitis B virus (HBV) infection on HIV disease progression. DESIGN: A prospective study of HIV-positive individuals from HIV diagnosis to diagnosis of AIDS or to the end of the follow-up period on 1 January 1991. Mean follow-up time was 62 months. SETTING: The study population was recruited from a primary health-care clinic for homosexual men and followed by linkage to the National AIDS Registry. PATIENTS, PARTICIPANTS: Of 876 individuals who were tested for HIV, 80 were HIV-positive and included for study. Two individuals were lost to follow-up. MAIN OUTCOME MEASURES: Differences in progression rates to AIDS according to HBV status at study entry. RESULTS: The adjusted relative risk of progression to AIDS for the 48 subjects who were HBV-antibody-positive at study entry was 3.6 [95% confidence interval (CI), 1.3-10.1]. A high frequency of receptive anal intercourse was also associated with more rapid HIV disease progression; adjusted relative risk 2.6 (95% CI, 1.1-5.9). CONCLUSIONS: Our results suggest that presence of HBV antibodies is associated with more rapid HIV-disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Structure-toxicity relationships in the amatoxin series. Structural variations of side chain 3 and inhibition of RNA polymerase II.

The amatoxins, highly toxic components of death cap Amanita mushrooms, bind strongly to RNA polymerase II (or B) in cell nuclei thus preventing the transcription of DNAs to hn-RNAs (Pre-mRNAs), the precursors of messenger RNAs. Three of the binding sites of the bicyclic octapeptides have been identified: an isoleucine side chain in position 6, a trans-4-hydroxyl group at proline in position 2 and a hydroxylated L-isoleucine side chain in position 3. No information exists about the stereochemical conditions at the beta-C-atom (C-atom 3) of this side chain. We have now synthesized the diastereomeric S-deoxo-amaninamides (Fig. 1) containing, in position 3, L-allo-isoleucine (analog 1), (2S, 3R)-2-amino-4-hydroxy-3-methyl butyric acid (analog 2), the diastereomer (2S, 3S)-2-amino-4-hydroxy-3-methylbutyric acid (analog 3) and D-isoleucine (analog 4). In the last synthesis, besides the "normal" bicyclic octapeptide 4, an isomeric Iso-4 was formed. The affinities for Drosophila RNA polymerase II were 100 times weaker as compared to gamma-amanitin for 1, 10 times weaker for 2, 200 times weaker for 3, 100 times weaker for 4, and more than 1000 times weaker for Iso-4. The results point to the importance of a methyl group in (R)-configuration at the beta-C atom of side chain 3.

Amanitins↗
PubMed1991

[Contact tracing in HIV infections].

The HIV counselling and testing clinic at the Oslo City Board of Health started in April 1986 to monitor its programme to encourage HIV-infected persons to inform their partners. By 1 April 1989, 65 of 233 potentially identifiable case contacts reported by 167 index patients had been tested and shown to be HIV-antibody positive. For 30 of the case contacts the main reason for seeking counselling and taking a HIV-antibody test was being told that their partner was HIV-infected. We discuss the effectiveness and acceptability of the programme.

Adolescent↗
PubMed1991

Identification of the genes coding for the second-largest subunits of RNA polymerases I and III of Drosophila melanogaster.

We have isolated cDNA and genomic clones of Drosophila melanogaster by cross-hybridization with a 658 bp fragment of the yeast gene coding for the second-largest subunit of RNA polymerase III (RET1). Determination of the sequence by comparison of genomic and cDNA regions reveals an ORF of 3405 nucleotides which is interrupted in the genomic sequence by an intron of 48 bp. The deduced polypeptide consists of 1135 amino acids with a calculated molecular weight of 128 kDa. The protein sequence shows the same conserved regions of homology as those observed for all the second-largest subunits of RNA polymerases cloned so far. The gene (DmRP128) obviously codes for a second-largest subunit of an RNA polymerase which is different from DmRP140 and DmRP135. We have purified three distinct RNA polymerase activities from D. melanogaster. By using specific RNA polymerase inhibitors in enzyme assays and by comparing their subunit composition we were able to distinguish between RNA polymerase I, II, and III. RNA polymerase preparations of D. melanogaster were blotted and the second-largest subunits were identified with antibodies raised against polypeptides expressed from DmRP128 and DmRP135. Anti-DmRP135 antibodies react strongly with the second-largest subunit of RNA polymerase I but do not react with the respective subunits of RNA polymerase II and III. The second-largest subunit of RNA polymerase III is only recognized by anti-DmRP128. Previously, we have claimed that DmRP135 codes for the second-largest subunit of RNA polymerase III.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Analysis of the promoter region of the housekeeping gene DmRP140 by sequence comparison of Drosophila melanogaster and Drosophila virilis.

To analyze the transcriptional control regions of Drosophila melanogaster household genes, we have characterized the promoter of the gene coding for the second-largest subunit of RNA polymerase II (DmRP140). Analysis of cDNA revealed that the coding region of the protein extends beyond the originally assumed transcription start point (tsp) and deduced translation start codon [Falkenburg et al., J. Mol. Biol. 195 (1987) 929-937] and that the tsp determined previously corresponds to an intron/exon boundary of an additional intron. Upstream of the polII gene we found a transcription unit that is transcribed in the opposite direction. The initiating ATGs of the two genes are only 467 nucleotides (nt) apart. The untranslated region is extremely A + T-rich (88%) but none of the transcription units is preceded by a canonical TATA element. It does not feature any other known nt sequence motifs thought to be necessary for the basic transcriptional machinery; yet, this region functions as a bidirectional promoter: a central 309-bp fragment directs transcription of a reporter gene in transiently transfected Drosophila culture cells in both orientations. The gene coding for the second-largest subunit of RNA polymerase II of Drosophila virilis (DvRP140) was isolated and partially analyzed. The gene is located on the second chromosome at 22F/23A which corresponds to the position determined for D. melanogaster.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

Conceiving a fetus for bone marrow donation: an ethical problem in prenatal diagnosis.

We present a family who sought prenatal diagnosis in order to bear a healthy child to serve as an HLA-identical bone marrow donor for their son affected with Wiskott-Aldrich syndrome. They intended to abort HLA-incompatible fetuses who would have been unsuitable bone marrow donors. This case led us to conclude that prenatal diagnosis should not be used to benefit a third party or facilitate the conception or abortion of a fetus for the purpose of generating an organ for transplantation. The limits of parental autonomy and physician responsibility are discussed.

Aborted Fetus↗