Extraction of an artery in rectal biopsy]

A biopsy of a rectal carcinoma has led to the extraction of a 2.5 cm arterial specimen, followed by an arterial bleeding. The cause of this exceptional complication was the presence of atypical vessels reaching the rectal lumen due to tumor ulceration.     

Pharmacokinetics of intravenously administered 125I-labelled human alpha 1-acid glycoprotein

The volumes of distribution of many acidic drugs have been shown to be close to that of their binding protein, i.e. serum albumin. The distribution of basic drugs mainly bound to alpha 1-acid glycoprotein (AAG) can be questioned with respect to its dependency upon the distribution of this plasma protein. So, a pharmacokinetic study was performed in 7 subjects with human 125I-labelled alpha 1-acid glycoprotein. The steady-state volume of distribution was found to be 5.37 +/- 0.82L. The central volume was 3.23 +/- 0.33L, close to that of plasma volume and the peripheral volume was 2.14 +/- 0.63L. These data allowed the establishment of an equation giving access to the volume of distribution of a basic drug by relating its unbound fraction to physiological distribution of alpha 1-acid glycoprotein. The values yielded by this equation show that the actual and calculated volumes of distribution of basic drugs mainly bound to AAG are discrepant. This protein is thus not the main factor controlling the distribution of basic drugs within the body.     

Effects of the immunomodulator diacetyl-splenopentin on antigen-induced arthritis in rabbits

Long-term treatment with the immunomodulator diacetyl-splenopentin reduces the severity of chronic joint inflammation and cartilage destruction in rabbits with antigen-induced arthritis. The level of specific antibodies as well as specific and non-specific cell-mediated immune reactivities including the proliferative response of spleen lymphocytes to cartilage proteoglycans in treated animals are lower than in untreated arthritic rabbits. Moreover, suppressor cell activity, which normally decreases during the early phase of inflammation, is enhanced and hyperreactive helper cell potential is reduced. These findings suggest that treatment with diacetyl-splenopentin normalizes the immune regulation, which is disturbed in the early phase of inflammation. This might result in a depression of the hyperreactive immune system including the autoimmunity developed against cartilage. Lowered immune reactivity in the joint in turn reduces the severity of chronic joint inflammation.Preliminary results were presented at the 6th Halle Summer Colloquium on Modulation, Mediation and Inhibition of Inflammation (H. Bekemeier and R. Hirschelmann, eds.). Wiss. Beitr. Martin-Luther-Universität Halle-Wittenberg 1987/7. Halle (Saale) 1987.     

Paracetamol inhibits replicative DNA synthesis and induces sister chromatid exchange and chromosomal aberrations by inhibition of ribonucleotide reductase

Effects of paracetamol have been studied in a hydroxyurea (HU)-resistant mouse mammary tumour cell line TA3H2, shown to overproduce the small subunit of ribonucleotide reductase. These TA3H2 cells were much more resistant than the TA3H (wild-type) cells towards the inhibitory effect of paracetamol on cell growth, IC50 0.55 mM paracetamol for the wild-type compared to 2.7 mM for the HU-resistant cells. The reduced cell growth was due to an inhibition of replicative DNA synthesis, judged from an increased percentage of cells in S-phase measured by flow cytometry. Furthermore, in the wild-type cells, the increase in the number of cells in S phase was already observed at 0.1 mM while in the HU-resistant cell line this effect was first seen at 3.0 mM paracetamol. HU inhibits ribonucleotide reductase by destroying a tyrosyl free radical located on the small subunit of the enzyme. By electron paramagnetic resonance we demonstrate that paracetamol added to crude cell extracts of HU-resistant cells also immediately destroys this radical. These results show that paracetamol reduces DNA synthesis by a specific inhibition of ribonucleotide reductase. A concentration-dependent induction of sister chromatid exchanges was found both with paracetamol (1.0-10 mM) and HU (0.3-3 mM) in wild-type cells whereas no such increase was observed in HU-resistant cells. Paracetamol (1 mM for 2 h) also increased the number of chromosomal aberrations CAs in wild-type cells (i.e. chromatid breaks and chromatid exchanges). The frequency of CAs was not increased in HU-resistant cells at paracetamol concentrations up to 10 mM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex ratio of the mutation frequencies in haemophilia A: coagulation assays and RFLP analysis.

Coagulation and RFLP data from 41 families with an isolated haemophilia A patient were used to estimate the sex ratio of mutation frequencies (nu/mu). Based on the results of coagulation assays in all the female relatives investigated, nu/mu was estimated to be 12.1 by the maximum likelihood method (95% confidence interval 3.8 to 62.5). In order to avoid the possible influence of germline mosaicism, an additional analysis was performed in which only the results in the mothers and grandmothers of an isolated patient were included. The nu/mu ratio was then estimated to be 5.2 (95% confidence interval 1.8 to 15.1). Because an estimate of nu/mu based on all available RFLP data can easily be biased in favour of males, we set up a model in which only information on the grandparental derivation of the patient's X chromosome was used, irrespective of the generation in which the mutation actually occurred. In this way nu/mu was estimated to be minimally 4. The probability of carriership for mothers of an isolated haemophilia A patient amounts to 86% with a sex ratio of 5.2. Although this would imply that 14% of the mothers are not carriers of the disease in the classical sense, they may be mosaic for the mutation and, therefore, also at risk of transmitting the mutation more than once.     

A staphylococcal radioimmunoassay for detection of antibodies toMycoplasma pneumoniae

A radioimmunoassay (RIA) which depends on the property of protein A ofStaphylococcus aureus to combine with the Fc-fragment of immunoglobulins was developed.This technique was employed to measure antibodies in human and various animal sera. It could be demonstrated that the staphylococcal RIA was at least as sensitive as the previously described radioimmunoprecipitation technique in detecting antibodies toM.pneumoniae in human sera. In addition, antibodies toM.pneumoniae could be demonstrated in sera of hamsters intranasally inoculated with the organisms. Antibodies could also be demonstrated in rabbit sera after immunization withM.pneumoniae. The test proved to be considerably more sensitive than conventional tests for detection of antibodies to the organisms. The test requires only small amounts of reagents and is relatively inexpensive.The results were presented in a preliminary form at the annual meeting of the Local Branch of the American Society for Microbiology, Frankfurt, March 1976 and the 77th ordinary meeting of the Society for General Microbiology, Glasgow, September 1976     

Colonization of in vitro-formed cervical human papillomavirus- associated (pre)neoplastic lesions with dendritic cells: role of granulocyte/macrophage colony-stimulating factor

The purpose of this study was to investigate the ability of CD1a+ Langerhans/dendritic cells (LCs/DCs) to infiltrate human papillomavirus (HPV)-associated (pre)neoplastic lesions of the uterine cervix. Migration of LCs/DCs in the presence of keratinocytes derived from normal cervix and HPV-transformed cell lines was evaluated in Boyden chambers and in organotypic cultures and correlated with granulocyte/macrophage colony-stimulating factor (GM-CSF) production by the cells, as determined by ELISA. Conditioned media of HPV-transformed keratinocytes contained lower amounts of GM-CSF and induced a decreased motile response of LCs/DCs in the Boyden chamber assay compared with those of normal cervical keratinocytes. The migration of LCs/DCs in the presence of conditioned media from normal keratinocytes could be blocked by an anti-GM-CSF antibody, and the migration of LCs/DCs in the presence of conditioned media from HPV-transformed keratinocytes could be increased by supplementing the media with recombinant GM-CSF. GM-CSF was also a potent factor in enhancing the colonization of LCs/DCs into organotypic cultures of HPV-transformed keratinocytes, as the infiltration of LCs/DCs in the in vitro-formed (pre)neoplastic epithelium was minimal under basal conditions and dramatically increased after the addition of GM-CSF to the cultures. These results suggest that GM-CSF could play an important role in the recruitment of LCs/DCs into the HPV-transformed (pre)neoplastic cervical epithelium and be useful as a new immunotherapeutic approach for cervical (pre)cancers.     

Multicontrast MRI of remyelination in the central nervous system

Although magnetic resonance imaging (MRI) represents the most sensitive tool for the detection of white matter abnormalities in patients with multiple sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes. In order to identify putative MRI markers for de- and remyelination, we employed the cuprizone mouse model which leads to a selective and reversible demyelination of the corpus callosum with little or no axonal damage. Apart from histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using multiple contrasts. While individual MRI findings significantly correlated with electron microscopy, the differentiation of regions with normal, demyelinated or remyelinated white matter by one contrast alone was less specific than by histology or electron microscopy. However, an accurate MRI prediction of the in vivo myelin status was achieved by a discriminant function analysis using a combination of T1, T2 and magnetization transfer contrast. With a correct assignment of 95% of all animals examined, the procedure will allow for the survey of new therapeutic approaches aiming at improved remyelination.     

Metachronous and multiple aneurysmal bone cysts: a rare variant of primary aneurysmal bone cysts

In 1942, Jaffe and Lichtenstein introduced the term aneurysmal bone cyst (ABC). Primary ABC is characterized by the presence of spongy or multi-cameral cystic tissue filled with blood. The process is benign, but it is locally destructive and has a high propensity for recurrence. In this paper, we present the third case of multiple metachronous primary ABCs as a rare variant of ABC. We describe the 10-year history of a 12-year-old boy with metachronous multiple primary ABCs at five different sites (right proximal humerus, right ulna, bilateral distal radius and right lateral clavicle). Furthermore, our patient suffered from vascular malformations, such as aortic isthmus stenosis, hypoplastic thoraco-abdominal aorta and bilateral renal artery stenosis. To date, in contrast to solitary ABC, the multiple lesions have been found more frequently in male individuals. Using interphase cytogenetics, we analyzed three of five of the patients ABCs and one of these was also analyzed by GTG-banding. No chromosomal abnormalities were found. Significantly, we excluded the missense mutation of codon 201 in guanine nucleotide-binding protein 1 gene consistently found in McCune-Albright syndrome (MAS) and in non-MAS cases of polyostotic fibrous dysplasia of bone with or without secondary ABC.