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J Kaufmann

Publications and source records attributed to J Kaufmann.

At least 19 recordsLinked to original sources

TGA cysteine codons and intron sequences in conserved and nonconserved positions are found in macronuclear RNA polymerase genes of Euplotes octocarinatus.

The gene sequences of the second largest subunits of RNA polymerases I and II of Euplotes octocarinatus, RPA2 and RPB2, were determined and compared to the respective known sequences of Saccharomyces cerevisiae. The similarity of the derived polypeptide sequences permitted their assignment to the respective polymerases and allowed the comparison of the zinc binding regions. In frame TGA codons were detected, which are likely to encode conserved cysteinyl residues in the putative zinc-finger region of the RPA2 gene. They were also found in other positions in both the RPA2 and RPB2 genes. The RPB2 gene contains a 30 bp intron close to the 5'-end of its coding region. The 5'-ends of the coding regions of all three genes encoding the largest subunits of the three different polymerases were also analyzed. The zinc finger structures again show the use of TGA codons for conserved cysteinyl residues in two of the genes. An N-terminal intron is located in the RPB1 gene at a conserved position as compared to the respective genes of several other eucarya.

Amino Acid Sequence

Gene dosage as a possible major determinant for equal expression levels of genes encoding RNA polymerase subunits in the hypotrichous ciliate Euplotes octocarinatus.

Ciliated protozoa harbor two different types of nuclei in each cell. The diploid micronucleus is the transcriptionally inactive generative nucleus, while the macronuclous contains a highly amplified transcriptionally active genome of lower complexity. The macronuclear genes encoding the two largest subunits of both RNA polymerases I and II of Euplotes octocarinatus were identified by a novel method of two step PCR walking, employing primer pairs derived from telomeric sequences of the organism and known conserved RNA polymerase polypeptide sequences, respectively. The relative gene dosage was determined. The genes are present in equal copy numbers for the respective matching subunits. Northern hybridizations showed comparable amounts of transcripts, as well, within the matching pairs. Mapping of the 5'-termini of the transcripts of the gene sized chromosomes showed that the upstream nontranscribed regions are very short and contain characteristic sequence motifs which could be the determinants of equal promoter strengths for subunits of a common RNA polymerase.

Amino Acid Sequence

Immunovisualization of high (HK) and low (LK) molecular weight kininogens on isolated human neutrophils.

An immunocytochemical study was performed to examine the cellular localization and the subcellular distribution of kininogens in human blood cells. Kininogens were visualised using the immunogold-silver staining method and confocal scanning laser microscopy. We confirmed the existence of high molecular weight kininogen in human neutrophils and describe for the first time the presence of low molecular weight kininogen on these cells. Both high and low molecular weight kininogens were restricted to the neutrophils where they localized as clusters of immunogold particles on the cell membrane. No labeling was observed intracellularly in organelles such as mitochondria, endoplasmic reticulum, and azurophilic or specific granules after permeabilization of the neutrophils with Triton X-100, a procedure that permitted the visualization of elastase in the azurophilic granules. Clusters of high molecular weight kininogen molecules attached to the neutrophil surface could serve as receptors for plasma kallikrein and/or be the source of substrate for a discrete and circumscribed formation of kinins that may in turn facilitate the local diapedesis of neutrophils and the transudation of plasma constituents during acute inflammation.

Antibodies, Monoclonal

The interaction of Trypanosoma congolense and Haemonchus contortus infections in trypanotolerant N'Dama cattle.

The interactions between Trypanosoma congolense and Haemonchus contortus infections were studied in N'Dama calves. A total of 38 N'Dama bulls was divided into four groups and each group infected either with H. contortus 1 week after infection with T. congolense or with T. congolense 4 weeks after infection with H. contortus, or with either infection singly. Parasitological (faecal egg counts, parasitaemia), haematological (packed cell volume, white blood cell counts, albumin) and clinical parameters (body weight change, mortality rate) were compared among the various groups. The results showed a reduced prepatent period and a markedly increased pathogenicity of H. contortus infections in animals with a concurrent T. congolense infection. The most harmful combination was a H. contortus infection 1 week after the T. congolense infection which resulted in a progressive and severe anaemia, accompanied by hypoalbuminaemia, increased weight loss and high mortality. The anaemia induced by dual infections showed a low responsiveness to chemotherapy and in several cases supportive treatment did not help recovery. The results also showed that animals with a concurrent T. congolense and H. contortus infection ran a higher risk of succumbing during the infection, and also during 10 weeks following treatment. Although infections with T. congolense alone produced no clinical signs, they were found to significantly reduce the ability of infected animals to mount a normal response to a subsequent H. contortus infection. It was concluded that the increased H. contortus egg excretion observed in animals infected with both parasites might significantly increase the risk of nematode infections and that the reduced prepatent period might necessitate more frequent anthelmintic treatments. These interactions should, therefore, be considered wherever attempts are made to control these two diseases.

Animals

Effect of erythropoietin on ischemia tolerance in anemic hemodialysis patients with confirmed coronary artery disease.

From a total of 81 patients on maintenance hemodialysis who underwent coronary angiography, 8 patients fulfilled the criteria: significant coronary artery disease, hematocrit less than 27%, reproducible (ECG) positive treadmill test, no disturbance of repolarization in ECG at rest. Exercise stress testing was performed at a hematocrit of 25 +/- 2% and following erythropoietin therapy at a hematocrit of 34 +/- 0.5%. Symptom-limited exercise performance increased in all patients (1.10 +/- 0.3 W/kg b.w. vs. 1.44 +/- 0.31 W/kg b.w., p less than 0.01) as well as exercise duration (489 vs. 362 s, p +/- 0.01). ST segment depression during maximal exercise was reduced from a mean of 2.1 to 0.4 mm (p less than 0.01). It is concluded that amelioration of renal anemia by erythropoietin in dialysis patients with significant coronary artery disease reduces exercise-induced myocardial ischemia.

Adult

A multicentred, two-year, phase III clinical trial of norethisterone enanthate 50 mg plus estradiol valerate 5 mg as a monthly injectable contraceptive.

Norethisterone enanthate (NET-EN) 50 mg combined with estradiol valerate (EV) 5 mg was studied as a once-a-month injectable contraceptive with regard to effectiveness, cycle control, adverse events and acceptability. In eight Family Planning Centres from 5 Latin American countries, 652 fertile women were followed-up for a period of 24 months, providing a total of 10,689 woman-months of experience. Only 1 pregnancy occurred, in the first treated month a few days before the second injection (failure rate 0.11 per 100 woman-years). Under treatment, the first cycle was drastically shortened in most cases, but thereafter cycles tended to recover to pre-treatment patterns. There was a significant decrease of hypermenorrhea and dysmenorrheic cycles. Intracyclic bleeding and spotting appeared in 1.2% and 2.4%, respectively, and amenorrhea in 2.5% of cycles. Incidence of other adverse events was very low with the exception of weight gain of 2 Kg (28%). Continuation rate at 12 months was 64.7%. The cumulative discontinuation rate due to bleeding problems was 7.4% and 10.7% due to adverse events at 24 months.

Adolescent

Mapping of the prekallikrein-binding site of human H-kininogen by ligand screening of lambda gt11 expression libraries. Mimicking of the predicted binding site by anti-idiotypic antibodies.

High molecular weight (H-)kininogen, a non-enzymatic cofactor of the contact activation system, has on the COOH-terminal part of its light chain a unique binding site which complexes prekallikrein or factor XI with high affinity and specificity. In a conventional protein fragmentation approach, the prekallikrein-binding site was mapped to positions 556-595 of the human H-kininogen sequence (Tait, J. F., and Fujikawa, K. (1986) J. Biol. Chem. 261, 15396-15401). To gain more insight into the minimum structural requirements of the prekallikrein-binding site, we have developed an alternative strategy employing the lambda gt11 expression cloning system. A ligand assay was established which probes for the binding site in H-kininogen or recombinant fusion proteins thereof by complexation with prekallikrein, followed by a specific antibody against prekallikrein and a secondary labeled antibody. A cDNA library constructed in lambda gt11 from random fragments of a cDNA clone encoding the COOH-terminal part of the kininogen light chain was screened by the ligand assay, and 17 positive clones were identified. Analysis of their inserted cDNA sequences revealed a consensus sequence of 119 nucleotides which maps to the extreme 3' end (positions 1759-1877) of the coding part of the prekininogen mRNA. The consensus sequence encodes positions 569-607 of the kininogen light chain and overlaps by 27 residues (positions 569-595) with the binding segment identified previously by the fragment approach. Analysis of successively shortened peptides revealed that the common segment of 27 residues but not truncated versions thereof contains the essential structural elements for prekallikrein binding. This conclusion was corroborated by the finding that anti-idiotypic antibodies toward a monoclonal antibody directed to the binding segment of 27 residues bear internal image(s) of the binding site of H-kininogen. It is pointed out that the methodology described in this study may prove generally useful in the cloning and mapping of high affinity binding sites of proteins.

Amino Acid Sequence

[Demonstrations].

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Adrenal Cortex Hormones

[Basaliomas after vaccination and infusion in basal cell nevus syndrome].

In a 31-year-old patient with a basal cell nevus syndrome two basal cell epitheliomas occurred through exogenous factors. The tumors appeared within 18 years after BCG vaccination and 3 years after an intravenous drip respectively. In basal cell nevus syndrome this course of development of basal cell carcinomas is seldom described.

Adult

[Comparison of the epidermodysplasia verruciformis Lewandowsky-Lutz with the other Papova virus acanthomas by light and electron microscopy (author's transl)].

Based on histology and electron microscopy, a series of Papova virus acanthomas consisting of 300 common warts and Condylomata acuminata as well as primary efflorescences of 7 typical and 7 questionable cases of Epidermodysplasia verruciformis have been classified. Four cytological types expressing different cytopathogenic viral actions were established. Typ 4 ("basophilic foamy giant keratinocytes") seems to be specific for Epidermodysplasia verruciformis which thus can be differentiated histologically against ordinary warts (type 1-3).

Condylomata Acuminata

SOluble and insoluble immune complex-platelet interactions in rheumatoid inflammation.

The interactions of soluble and insoluble immunoglobulin G (IgG) complexes with macromolecular rheumatoid factor (RF) and platelets were examined in an in vitro system permitting observation of platelet activities which may contribute to rheumatoid inflammation. Studies of the aggregation phenomenon by the nephalometric technique and by selective sedimentation of 51Cr-labelled platelets revealed no aggregation by platelets exposed to heat aggregated IgG (HAIgG) complexes or their RF precipitates in a plasma test system. Release of serotonin was demonstrated by the increasing radioactivity of platelet supernates to 45 min by 14C-serotonin labelled platelets exposed to insoluble IgG heat aggregates. Significantly less release was shown with saline, native IgG, and soluble IgG complexes. When RF was added to soluble HAIgG complexes, the resulting precipitate caused significantly higher release than controls. No concomitant release of the lysosomal enzyme beta-glucuronidase was detected. Thus, although soluble complexes do not cause significant release of biologically active amines, conversion of soluble complexes to insoluble immune precipitates by RF is associated with this activity which is independent of platelet aggregation and/or lyosomal enzyme release in our test system. Release of biologically active amines from platelets exposed to insoluble complexes may be important in the initiation and propagation of inflammation in rheumatoid arthritis.

Antigen-Antibody Complex

[Therapy of androgenization symptoms: double blind study of an antiandrogen preparation (SH B 209 AB) against neogynon (author's transl)].

The antiandrogen-containing preparation SH B 209 AB was tested in comparison with an ovulation inhibitor with no antiandrogenic effect (Neogynon) in a randomized, double blind study conducted to determine the effects of both on androgenization symptoms. 88 patients took part in the study. In the majority of cases the duration of the treatment period was more than 6 months. It was shown that the therapy with the combination preparation containing cyproterone acetate was distinctly more successful in cases of acne and seborrhoea: not only acne in its various locations but also all forms of seborrhoea were more favourably influenced by the trial preparation. This difference was statistically significant (p less than 0.05). It was not possible to establish a significant difference between the two preparations in the case of hirsutism in its various locations from the limited number of cases observed. There were also no differences detected in hepatic tolerance. During treatment with both preparations all values measured were within the normal range.

Acne Vulgaris