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Biomedical subjects

K Weise

Publications and source records attributed to K Weise.

At least 19 recordsLinked to original sources

Relationship between HLA I surface expression and different cytopathic effects produced after herpes simplex virus infection in vitro.

In the present study, we investigated the effects of herpes simplex virus (HSV) infection on the expression of HLA class I antigens and beta 2-microglobulin in human fibroblasts. The mRNA abundance for HLA class I was shown to be strongly reduced after infection with HSV strains either producing cell rounding or fusion from within (FFWI), however, HLA class I expression on the surface of cells is strongly reduced only after appearance of FFWI. Using a ts mutant (ts 78R) or CyA in combination with a fusion from without (FFWO) inducing strain of HSV, this loss of HLA class I antigens is assumed to be correlated to the rearrangement of the cell membrane during the fusion process itself as a late event of cytopathogenicity.

Blotting, Northern

Vaginal infection of mice with HSV type 2 variant ER-: a new animal model for human primary genital HSV type 2 infections.

Studying the pathogenesis of vaginal infections in mice with two variants of Herpes simplex virus type 2 (HSV-2) strain ER we observed that both variants ER+ and ER- caused severe vaginitis but only ER+ invaded the CNS leading to lethal neurological disease. In contrast, mice infected with ER- cleared the virus from the vagina and recovered from infection. ER+ and ER- expressed equal levels of thymidine kinase (TK) indicating a TK-independent difference in neurovirulence. Using the non-neurovirulent variant ER-, we were able to investigate humoral immune responses later after infection. Vaginal infection with ER- suppressed serum antibody formation after a secondary systemic HSV-1 infection. Fresh isolates of HSV-1 and HSV-2 caused uniformly a lethal neurological disease after vaginal inoculation of mice. However, some animals survived an intraperitoneal infection with these isolates. Infection with HSV-1 isolates stimulated a strong antibody production, whereas infection with HSV-2 isolates suppressed antibody formation, thus supporting earlier results from our group obtained with laboratory strains. Since suppression of antibody formation could be demonstrated with clinical HSV-2 isolates and likewise after vaginal infection with HSV-2 variant ER- we consider this phenomenon to be of relevance in human genital HSV-2 infections. Vaginal infection of mice with variant ER- represents a new model for primary genital HSV-2 infections; this model could be useful for histopathological, virological, immunological and drug testing studies.

Animals

[Injuries in track and field sports].

Acute injuries in track and field sports are rare compared to team or combatant sports (accident rate 0.4%-1%). Acute lesions are most frequent in the muscular system, followed by ruptures of the larger tendons as well as of the ligaments and capsule of the large joints. More frequent are the so-called chronically recurrent microlesions due to false or excessive strain and "endogeneous injuries." Pain at the insertions of the great tendons belongs to this category, for instance achillodynia, the so-called shin splint at the tibia, and jumper's knee involving the patella tendon. Operative treatment of muscle tears is only considered in cases of bigger extent, i.e. in 1/3 of the whole muscle diameter. Disruptions of the great tendons especially at the leg as well as unstable injuries of the capsular ligaments are an indication for reconstructive surgery. In cases of chronic sports injuries due to recurrent overstrain the noxious agent must be eliminated as a preventive step accompanied by some conservative methods of treatment. Stretching and warming up in combination with step-by-step rehabilitation training are of special importance.

Athletic Injuries

Characterization of fusion from without induced by herpes simplex virus.

The process of fusion from without (FFWO) induced by herpes simplex virus (HSV) was analyzed by using various inhibitors and compared to fusion from within (FFWI). The fate of certain elements of the cytoskeleton after FFWO was also investigated. Our experiments demonstrate FFWO as a very suitable system for study of early virus-cell interactions. Zn++ ions proved inhibitory for penetration whilst pretreatment of cells with Ca++ ions before infection enhanced FFWO activity. Dissociation of penetration from the fusion process itself was possible by use of Zn++ ions, low pH-treatment and antiserum on the one hand and N-ethylmaleimide and cytochalasin D on the other. Penetration itself needs only 6 min or less to proceed. FFWO is independent of inhibitors of glycosylation (tunicamycin) and intracellular vesicular traffic (monensin), protein-synthesis (cycloheximide) and energy-delivery (2.4 dinitrophenol and Na-azide). Analyzed strains of HSV-1 and -2 producing FFWI could be subgrouped into three categories: Strain ANG with high, strain HFEM and Lux with low and strains IES, Len, MP, US with no FFWO activity. The results of these experiments indicate that the property of FFWO is not purely a consequence of the number of PFU but depends on certain inherent properties of the virus particles. Addition of heparin as well as treatment of cells with heparitinase effectively prevented FFWO, indicating identical virus receptors for entrance of virus into cells and FFWO. During our studies several calf sera were found to inhibit FFWO-activity. Inhibition of FFWO by a glycoconjugate (ferritin coupled with oleic acid) indicates specific stereochemical hindrance of FFWO by this compound. Shortly after FFWO the actin filaments rearrange to form long fibres and surface fibronectin is being lost from the cell membrane.

Animals

Differentiation of herpes simplex virus-induced fusion from without and fusion from within by cyclosporin A and compound 48/80.

Treating strains of herpes simplex virus (HSV) in culture with either cyclosporin A or compound 48/80, allowed the strains to be divided into two groups. Group 1 contains the strains ANG and HFEM of HSV-1 and Lux syn (HSV-2) producing fusion from within (FFWI) and fusion from without (FFWO). Cyclosporin A fails to inhibit both types of fusion at concentrations up to 100 microM. Strains ANG and HFEM belong to the syn 3 marker locus group identified for HSV-1. Group 2 contains all other fusion-producing strains of HSV tested so far. Cyclosporin A inhibits FFWI at concentrations as low as 10 to 20 microM. These strains belong to the syn locus marker groups 1, 2, 4 and 5. From the fact that mutations in glycoprotein B belong to the syn 3 marker group we conclude that glycoprotein B is of major importance for FFWO. Compound 48/80 also differentiates between these two groups of viruses. O-Acetyl cyclosporin A is unable to inhibit FFWI induced by group 2 viruses; in contrast, cyclosporin H and the Ca2+ ionophore A23187 exert inhibition effects similar to those exerted by cyclosporin A. We conclude from the effects of these compounds that binding properties of the OH group of cyclosporin A and an increase of Ca2+ ions may be preconditions for the observed effects. Binding of cyclosporin A to cyclophilin does not appear to be responsible for these effects.

Animals

Colonization of adrenal glands and ovaries of mice by HSV-2 variants. I. Virological studies.

HSV-2 strain ER was shown to consist of variants with different pathogenic phenotype: Variant ER+ replicates to high titers in the adrenal glands and the ovaries but much less in the spleen; the testes were not colonized. ER+ migrates to the spinal ganglia and is highly neuroinvasive after i.p. inoculation. Variant ER- replicates 100-1,000 fold less in the adrenal glands and the ovaries, but proceeds to the spinal ganglia without invading the CNS. However, both variants are highly neuropathogenic after direct i.c. injection. We conclude that neuropathogenicity, neuroinvasiveness and the ability to replicate in the adrenal glands as well as ovaries are each determined by different sets of genes. Replication in mouse embryo fibroblasts--but not in Vero and adreno cortical carcinoma Y1 cells--is different for both strains. Also the adsorption capacity to cultured cells differs as shown by addition of D.S. 500. ER- is eliminated from the blood stream more quickly than ER+. Finally, C. parvum reduces the rate of replication of both variants in the adrenal and the ovaries. It is concluded that different adsorption and replications rates of variants ER+ and ER- in cell types critical for spread of HSV are responsible for the different pathobiological properties.

Adrenal Glands

Change of processing and nucleocytoplasmic transport of mRNA in HSV-1-infected cells.

A monoclonal antibody (MAb) raised against the pore-complex lamina fraction from CV-1 cells was used to study alterations of gene expression in herpes simplex virus type 1 (HSV-1)-infected cells. This MAb, which recognized only one cellular polypeptide of 60,000 Da, selectively stained the nucleus in immunofluorescence microscopy, showing a punctuated pattern either at the nuclear surface or at the nuclear rim. By immunoelectron microscopy, the p60 antigen could be localized in the nuclear pore complex structure. Infection of CV-1 cells with HSV-1 resulted in a drastic change of the nuclear staining pattern. Four hours p.i., a clustering of the p60 antigen and, 12 h p.i., a formation of finger-like holes, penetrating the nucleus, occurred. Later in infection (22 h p.i.) the antigen was found to be almost absent. By RNA blot hybridization it was demonstrated that, after HSV-1 infection, the level of cellular mRNA (beta-tubulin) gradually decreased, while the level of HSV major DNA binding protein (DBP) mRNA increased, reaching maximal level 3-6 h p.i. Interestingly, the level of beta-tubulin gene transcripts changed differentially in the polysomal and in the nuclear fraction during the initial phase of infection, in contrast to the viral DBP transcripts, indicating that, after HSV infection, host cell transcripts accumulate in the nucleus. Evidence is presented indicating that this change is not due to altered nucleocytoplasmic mRNA transport but is due to an impaired splicing of host cell transcripts in HSV-infected cells. The MAb, directed against the nuclear pore p60 antigen, strongly inhibited the ATP-dependent efflux of both cellular and viral mRNA from isolated nuclei. The ATP-dependence of the efflux did not change during viral infection. However, the inhibitory potency of the MAb was found to be lost at the final stage of HSV infection, paralleling the loss of p60 antigen.

Adenosine Triphosphate

[Change in external fixator and when in multiple trauma patients].

External fixation of fractures in polytraumatized patients normally should be regarded as temporary. After the patient's general condition is stabilized, in most cases it is necessary to change the procedure in order to provide sufficient mobility of joints, timely bony healing and early mobilisation. The earlier the transition toward internal osteosynthesis, the lower the complication rate. The follow up of 37 polytraumatized patients who were subjected to 50 changes of method after primary external fixation is described.

Adult

[Lateral ligament injury of the anterior ankle joint in sports].

During the last few years adequate therapy of ruptures of the fibular ligaments has been a subject of controversial discussions. Several authors consider operative and functional treatment to be almost equally good. In a retrospective study recent ankle ligament ruptures in 120 athletes were analysed with regard as to how the accident happened, the condition of the used sport shoe and the correlation between radiology and intraoperative findings. All cases were treated operatively because of an instability exceeding 10 degrees in the a.p.-stress X-ray. In a follow-up examination including 80 patients 35 to 46 months after operative reconstruction subjective complaints, ability for sports as well as clinical and radiological findings were taken into consideration. Special attention was paid to the possibility of degenerative lesions after plaster immobilisation and to the results of x-ray stress stability examinations. The result of our study confirmed the superiority of operative reconstruction of a two-ligament-injury including a p.o. cast immobilisation. There were only a few cases with functional impairment or limitation of sports activities. No degenerative change could be detected via x-rays. In respect of literature studies, and based on our results, we recommend an individually adapted therapy concept depending on the special situation of the patient. Our follow-up treatment consists of early functional exercises in a windowed cast and a total immobilisation time with a walking plaster of 4 weeks. Alternative methods like the special shoe by Dr. Spring or functional splints are recommended for exceptional cases only.

Adolescent

[Clinical experiences with tetrachlorodecaoxide in the local treatment of difficult-to-heal wounds].

Local treatment of difficult wounds with TCDO, a chemically stable, water-soluble compound containing oxygen in a chlorite matrix, is supposed to increase the pO2 in hypoxic wound tissue and to amplify physiological responses of phagocytes in wounds. 21 patients were assigned to two groups, treated by TCDO impregnated dressings twice a day or by TCDO combined with temporary skin coverage Epigard. Daily records of the state of the wounds with regard to exudation, wound cleansing, formation of granulation tissue and epithelisation demonstrated the therapeutic effect of TCDO in the treatment of complicated wounds when primary surgical debridement was sufficient.

Adolescent

[Some developmental questions on the organization of psychiatric care in East Germany--25 years after Rodewisch].

Following an appreciation of the recommendation made 25 years ago at the Rodewisch symposium on the organisation of psychiatric care in the DDR, verious misconceptions and impediments affecting the development at a complex system of psychosocial care at Area Health Authority level are discussed, with special attention to securing the care of the chronically mentally sick and handicapped and the mentally retarded. The paper indicates current requirements in obtaining the further acceptance of a gradually achievable system of area care.

Chronic Disease

[Psychiatric care in Leipzig--10 years' regionalized care in a large city by 3 major clinics].

The paper deals with experience gained in the town of Leipzig in the course of the implementation of the regionalized organisation of psychiatric care. The idea behind the organisational structure is that of a complete psychiatric system of treatment, covering hospitalised, partially hospitalised, and out-patient treatment, supported by ancillary services, to provide continued care. The organisational structure has proved effective for basic psychiatric care in a large town.

Affective Disorders, Psychotic

Endocrine manifestations of critical illness in the child.

The stress response in humans commonly includes elevations in plasma concentrations of glucocorticoids, catecholamines, glucagon, growth hormone, aldosterone, and renin, resulting in alterations in the metabolism of glucose and other energy substrates, and in increased sodium and water retention. In severe illness, triiodothyronine and sometimes thyroxine are decreased without evidence of clinical hypothyroidism. Antidiuretic hormone may be elevated in bacterial meningitis and other central nervous system disorders, as well as in acute asthma, chronic ventilator therapy, pneumothorax, atelectasis, and postoperatively. Increased ADH concentration can lead to significant hypoosmolality and hyponatremia with adverse effects on the patient. In the setting of severe intracerebral insults, ADH may be inappropriately low, resulting in diabetes insipidus. Insulin concentrations may be inappropriately low for serum glucose concentration, or insulin may have diminished receptor responsiveness in seriously stressed patients. Either situation leads to hyperglycemia. Disturbances in calcium, phosphorus, and magnesium homeostasis may occur relatively frequently in the critically ill patient in response to therapeutic interventions, or illness-induced altered metabolism. It is not always clear when an altered metabolic or hormonal state is an appropriate response to a stress, or represents decompensation of the body's mechanisms for coping with that stress. It is important, however to recognize the common responses of the organism to severe illness, and to monitor for treatable abnormalities which occur.

Aldosterone

Replacement of glycoprotein B gene sequences in herpes simplex virus type 1 strain ANG by corresponding sequences of the strain KOS causes changes of plaque morphology and neuropathogenicity.

DNA sequences encoding glycoprotein B (gB) derived from herpes simplex virus type 1 (HSV-1) strain KOS321 were transferred to HSV-1 ANG. In cotransfection experiments the cloned HSV-1 KOS BamHI G fragment served as donor, and genomic DNA of two ANG variants as recipients. One of these variants, HSV-1 ANG path, expresses gC and the other, C18, was a spontaneous gC-negative mutant. Both ANG strains are of the syncytial (syn) phenotype whereas HSV-1 KOS321 is non-syncytial (syn+). Recombinants were identified by means of a monoclonal antibody which selectively recognizes gBKOS. Among the HSV-1 ANG path/gBKOS recombinants, the majority displayed an altered plaque morphology, i.e. they were of the syn+ phenotype. In contrast all of the C18/gBKOS recombinants were of the syn phenotype. The possibility that the mutant C18 carries a syn mutation not present in the parental strain could be excluded. Marker transfer experiments involving subfragments of the gB gene mapped the syn mutation of HSV-1 ANG path to a locus within the gene that has been previously termed syn 3. Subclones of HSV-1 ANG path were established either directly or after intermittent transfection or cotransfection with the KOS BamHI G fragment. The pathogenicity in mice of these clones was compared. The data obtained indicated that at high frequency, the BamHI G fragment confers apathogenicity.

Animals