The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage

Summary The coagulation cascade has a potential role in brain edema formation due to intracerebral hemorrhage. In this study blood and other solutions were injected stereotactically into the right basal ganglia in rats. Twenty-four hours following injection, brain water and ion contents were measured to determine the amount of brain edema. Intracerebral blood resulted in an increase in brain water content. The amount of brain edema surrounding the intracerebral hematoma was reduced by a thrombin inhibitor Na-(2-Naphthalenesulfonylglycyl)-4-amidino-DL-phenylalaninepiperidide, (-NAPAP) infused into the hematoma after the clot had been allowed to solidify. The inhibitor did not alter the actual size of the clot mass. An artificial clot composed of fibrinogen, thrombin, and styrene microspheres also produced brain edema. A fibrin clot led to edema formation even in the absence of mass effect provided by the microspheres. The single component responsible for production of brain edema in all these models was thrombin. The edema was formed in response to a fibrinogen-independent pathway. These results indicate that the coagulation cascade is involved in brain edema that develops adjacent to an intracerebral hematoma.     

The possible role of TNF-α and IL-2 in inducing tumor-associated metabolic alterations

This study was conducted to investigate the role of tumor necrosis factor- (TNF-) and interleukin-2 (IL-2) in inducing cancer cachexia, and the results were compared with those obtained from our previous study on Fisher 344 rats with methylcholanthrene-induced sarcoma. Three groups of male Fisher 344 rats received one of the following regimens: 4×10⁴ IU of human recombinant TNF- per rat per day subcutaneously (sc) for 5 consecutive days (n=5), 3.5×10⁵ U human recombinant IL-2 per rat per day sc for 14 consecutive days (n=5), or normal saline (n=5). The activities of both phosphoenolpyruvate carboxykinase (PEPCK) and malic enzyme (ME) were increased slightly in the IL-2 group. Furthermore, LPL activity was significantly increased in the adipose tissue of the TNF group and in the cardiac muscle of the IL-2 group, but not in that of the TNF group. These results show that there is a significant difference between the metabolic alterations seen in the tumor-bearing state and those induced by either TNF- or IL-2 alone. Thus, it is unlikely that IL-2 or TNF- is the sole mediator of cancer cachexia in this tumor and rat model.     

Effects of 1α,25-dihydroxy-vitamin D3 and calcipotriol on organotypic cultures of outer root sheath cells: a potential model to evaluate antipsoriatic drugs

In the human hair follicle, outer root sheath (ORS) cells constitutively express the hyperproliferation-associated keratins 6, 16 and 17 instead of keratins 1 and 10 found in interfollicular epidermis. In organotypic cultures, ORS cells form a stratified epithelium which in many respects resembles psoriatic skin: it has a hyperplastic tissue architecture and a poorly developed granular layer, and expresses hyperproliferation-associated keratins. Therefore, we studied the effects of the antipsoriatic compounds 1,25-dihydroxy-vitamin D₃ (1,25-(OH)₂-D₃) and its synthetic derivative calcipotriol on cultured ORS cells. In monolayer cultures, 10^–6 M 1,25-(OH)₂-D₃ or calcipotriol completely blocked ORS cell proliferation. This inhibitory effect was substantially reduced at 10^–8 M. Incubation of organotypic ORS cultures with both vitamin D analogues resulted in a marked thinning of the living cell compartment concomitant with a thickening of the horny layer. A reduced expression of differentiation markers such as keratins 10,16 and 17, involucrin and filaggrin paralleled the thinning of the stratum Malpighi. As determined by quantification of BrdU-positive cells, ORS cell proliferation was apparently not affected by the vitamin D analogues, indicating that these compounds mainly operate by accelerating the differentiation pathway within the suprabasal living cell compartment. No alteration in the expression of the 6- and 1-integrin chains was found.     

Experience with the PCR-based HLA-DQα DNA typing system in routine forensic casework

Summary The results of HLA-DQ typing from 42 routine forensic cases using the polymerase chain reaction (PCR) were analyzed regarding the reliability, discrimination efficiency and informative value of this system in a given case. The cases included stain typing from a variety of different substrates, i.e. blood and semen stains, mixed body fluids, single hairs, cigarette butts, material from fingernail scratches, as well as identification and paternity cases on postmortem and fixed tissue. A total of 125 individual stain and tissue samples were included. PCR amplification was achieved in 70% of these samples. In cases with mixed body fluids, e.g. sperm and vaginal cells from rape cases, DQ typing was always carried out successfully. However, only approx. 42% of all samples that could be typed were relevant regarding the inclusion or exclusion of a suspect. This was mostly due to the limited number of alleles that can be typed at the HLA-DQ locus or to the fact that the stain or hair samples did not originate from the perpetrator, but from the victim or from other persons not related to the crime.     

A soluble androgen receptor in the cytoplasm of the male mastomys prostate

Summary A steroid receptor protein was isolated from the cytoplasmic fraction of Mastomys prostate. Following in vivo and in vitro labelling of the tissue with tritiated testosterone or dihydrotestosterone, samples were analysed by gel exclusion chromatography or sucrose density gradient centrifugation. A steroid receptor complex was isolated on Sephadex G-200. Analysis of the steroids associated with this complex showed that the major part of the bound radioactivity was 5 -dihydrotestosterone. The binding was inhibited by unlabelled testosterone and could not be demonstrated in the liver cytosol. Using sucrose desity gradient centrifugation, the dihydrotestosterone receptor complex sedimented at 5.6 s together with heavier aggregates. In the presence of 0.4 M KCl a single complex was sedimented at 4. 6 s. The results demonstrate a receptor protein in the cytosol of the Mastomys prostate which binds to dihydrotestosterone and is comparable to that of rat prostate.     

Effects of enkephalins and two enzyme resistant analogues on monoamine synthesis and metabolism in rat brain

Summary Methionine-enkephalin and leucineenkephalin, administered into the lateral ventricle of intact rats, increased the accumulation of DOPA by a naloxone-sensitive mechanism in different brain regions after inhibition of the aromatic l-amino acid decarboxylase. Because of the rapid enzymatic degradation of both enkephalins large doses (500 g) were required to enhance brain catecholamine synthesis. The two enzyme resistant enkephalin analogues d-Ala²-methionine enkephalin amide (DALA (4–256 g) and FK 33-824 (0.003–1 g) also increased the synthesis of DOPA, dose-dependently and by naloxone-sensitive mechanisms, but at much lower dosage level. The enkephalins markedly enhanced the brain tyrosine concentration but this effect was not antagonized by naloxone, probably because the enzymatic cleavage releases tyrosine from the administered peptides. In contrast, neither DALA nor FK 33-824 increased the brain tyrosine concentration. The formation of 5-HTP and the brain tryptophan concentration were also increased by the enkephalins, although these effects were not blocked by naloxone. The enkephalin analogues, however, enhanced the formation of 5-HTP and the brain tryptophan concentration by naloxonesensitive mechanisms. All four peptides accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine after inhibition of monoamine synthesis. The results suggest that endogenous enkephalins, through the activation of opiate receptors, are involved in the short-term regulation of central monoaminergic systems.Preliminary data were presented at the Nobel Symposium 42, Principles for the Central Regulation of the Endocrine System, Stockholm, June 8–10, 1978, and at the 4th International Catecholamine Symposium, Asilomar Conference Center, Pacific Grove, California, September 17–22, 1978