Diisopropylglutathione ester protects A549 cells from the cytotoxic effects of sulphur mustard

The A549 cell line was used to assess the ability of diisopropylglutathione (DIPE) to protect against a 100 microM challenge dose of sulphur mustard (HD) using gentian violet (GV), thiazolyl blue (MTT) and neutral red (NR) assays as indicators of cell culture viability. As part of a continuing study of the efficacy of protective nucleophiles as candidate treatments for HD poisoning, several different combinations of protectant and HD were used to determine the optimal means of protecting A549 cells from the effects of HD. It was found that DIPE (4 mM) could protect cells against the effects of HD though for optimal effect, DIPE had to be present at the time of HD challenge. Cultures protected with DIPE were up to 2.9-fold more viable than HD exposed cells 48 h after HD challenge when using the GV, MTT and NR assays to assess viability. Observations by phase contrast microscopy of GV stained cultures confirmed these findings. Pretreating A549 cultures with DIPE for 1 h followed by its removal prior to HD challenge did maintain cell viability, though at a relatively low level (only up to 1.4-fold more viable than HD only exposed cells). DIPE was also able to protect HD exposed A549 cultures when added to cell cultures at intervals of up to 12 to 15 min after the initial HD exposure, though viability tended to decrease over this period, so that at 1 h, addition of DIPE did not maintain the viability of the cultures. This is the first such report of the anti-HD protectant properties of DIPE in A549 cells. It is concluded that the protection observed against HD is probably largely due to extracellular inactivation of HD by DIPE.     

The cytogenetics of lipomatous tumours

Transglutaminases are a family of calcium-dependent enzymes that catalyse the formation of covalent crosslinks between proteins. They have several diverse functions and are thought to be involved in cell differentiation, apoptosis and blood coagulation. We have investigated the expression of tissue transglutaminase in five fibrillary astrocytomas, five anaplastic astrocytomas and seven glioblastomas by immunohistochemistry. Strongly labelled tumour cells were seen in most of the fibrillary and anaplastic astrocytomas and all of the glioblastomas. Labelling was particularly prominent in the pseudopalisading tumour cells that surrounded foci of necrosis and apoptosis in glioblastomas. Most of the immunostained cells did not themselves show morphological features of apoptosis. In addition, apoptotic cells were demonstrated using in situ end-labelling and by in situ hybridization with digoxigenin-labelled poly(A) oligonucleotide probes. Apoptotic cells demonstrated by both of these methods were most numerous in anaplastic astrocytomas and glioblastomas. However, their distribution did not correlate with that of the tumour cells showing transglutaminase labelling. Strong transglutaminase labelling was also observed in the endothelial cells of vessels showing microvascular proliferation in all of the glioblastomas studied. In contrast, endothelial transglutaminase labelling was weak or absent in lower grade astrocytic tumours. Enhanced expression of transglutaminase by endothelial cells in glioblastomas may contribute to the high prevalence of vascular thrombosis and necrosis in these tumours.     

Sexual differentiation of the vertebrate brain: principles and mechanisms

A wide variety of sexual dimorphisms, structural differences between the sexes, have been described in the brains of many vertebrate species, including humans. In animal models of neural sexual dimorphism, gonadal steroid hormones, specifically androgens, play a crucial role in engendering these differences by masculinizing the nervous system of males. Usually, the androgen must act early in life, often during the fetal period to masculinize the nervous system and behavior. However, there are a few examples of androgen, in adulthood, masculinizing both the structure of the nervous system and behavior. In the modal pattern, androgens are required both during development and adulthood to fully masculinize brain structure and behavior. In rodent models of neural sexual dimorphism, it is often the aromatized metabolites of androgen, i.e., estrogens, which interact with estrogen receptors to masculinize the brain, but there is little evidence that aromatized metabolites of androgen play this role in primates, including humans. There are other animal models where androgens themselves masculinize the nervous system through interaction with androgen receptors. In the course of masculinizing the nervous system, steroids can affect a wide variety of cellular mechanisms, including neurogenesis, cell death, cell migration, synapse formation, synapse elimination, and cell differentiation. In animal models, there are no known examples where only a single neural center displays sexual dimorphism. Rather, each case of sexual dimorphism seems to be part of a distributed network of sexually dimorphic neuronal populations which normally interact with each other. Finally, there is ample evidence of sexual dimorphism in the human brain, as sex differences in behavior would require, but there has not yet been any definitive proof that steroids acting early in development directly masculinize the human brain.     

Cryotherapy of liver metastases. Initial results

PATIENTS AND METHOD: Between 1 Jan 1996 and 1 Apr 1998 29 patients underwent cryosurgical therapy for liver metastasis at the Department of Surgery at the University of Mainz. RESULTS: No complications occurred following cryosurgery alone (n = 12). Within the group of patients with a combined procedure (n = 11) 1 patient had temporary liver failure and 1 patient died of sepsis. Following freezing of the cutting zone (n = 6) 1 patient showed a bile fistula and 1 ascites. In 15 cases of 28 dismissed patients with remaining destroyed tumor tissue the follow-up showed no tumor recurrence (median follow-up 11 months). On the other hand 9 patients had a tumor recurrence within the liver, 3 patients at extrahepatic regions and 7 patients developed a tumor recurrence within the freezing zone.     

Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells

Pseudomonas aeruginosa, an opportunistic human pathogen, causes acute pneumonia in patients with hospital-acquired infections and is commonly associated with chronic lung disease in individuals with cystic fibrosis (CF). Evidence suggests that the pathophysiological effects of P. aeruginosa are mediated in part by virulence factors secreted by the bacterium. Among these factors is pyocyanin, a redox active compound that increases intracellular oxidant stress. We find that pyocyanin increases release of interleukin-8 (IL-8) by both normal and CF airway epithelial cell lines and by primary airway epithelial cells. Moreover, pyocyanin synergizes with the inflammatory cytokines tumor necrosis factor alpha and IL-1alpha. RNase protection assays indicate that increased IL-8 release is accompanied by increased levels of IL-8 mRNA. The antioxidant n-acetyl cysteine, general inhibitors of protein tyrosine kinases, and specific inhibitors of mitogen-activated protein kinases diminish pyocyanin-dependent increases in IL-8 release. Conversely, inhibitors of protein kinases C (PKC) and PKA have no effect. In contrast to its effects on IL-8 expression, pyocyanin inhibits cytokine-dependent expression of the monocyte/macrophage/T-cell chemokine RANTES. Increased release of IL-8, a potent neutrophil chemoattractant, in response to pyocyanin could contribute to the marked infiltration of neutrophils and subsequent neutrophil-mediated tissue damage that are observed in Pseudomonas-associated lung disease.     

Occupational stress: measuring job pressure and organizational support in the workplace

Person-environment fit and demand-control theoretical models developed to explain stress and strain in the workplace have guided the construction of most measures of occupational stress. The strengths and limitations of 8 job stress measures are briefly reviewed, and the Job Stress Survey (JSS), designed to assess the severity and frequency of occurrence of 30 specific sources of occupational stress, is described in some detail. Factor analyses of responses to the JSS items identified Job Pressure and Lack of Organizational Support as major dimensions of occupational stress for male and female employees in a wide variety of work settings. JSS Index, scale, subscale, and item scores assess general and specific aspects of the work environment that are most distressing for individual workers and that adversely affect groups of employees.     

Cerebral mucormycosis after liver transplantation: a case report

A fatal case of cerebral mucormycosis occurring shortly after liver transplantation is described. The patient was a 32-yr-old male with advanced end-stage liver disease manifested by tense ascites, spontaneous bacterial peritonitis, deepening jaundice and anuria requiring hemodialysis. The 3rd day after successful liver transplantation the patient developed acute respiratory failure, then focal motor signs. Computed tomography showed fluid in the left maxillary sinus, partial opacification of the ethmoid and sphenoid sinuses, and diffuse low density lesions in both cerebral hemispheres. Despite treatment for cerebritis and cerebral edema, the patient's pupils became fixed and dilated, and brain death was declared. Autopsy revealed mucor sinusitis and cerebritis. Mucormycosis is an opportunistic fungal infection occurring in patients with diabetic ketoacidosis, malignancy, or immunodeficiency, and in those receiving wide-spectrum antibiotics, corticosteroids, or cytotoxic therapy. Mucor most frequently involves the face, rhinocerebral disease predominating. These infections are difficult to treat, but are curable with aggressive and frequent surgical debridement, discontinuation or reduction of immunosuppressive therapy and amphotericin. The diagnosis of mucormycosis is very difficult to make in cases such as the present one, in which the typical presentation and classical signs are not present. A high index of suspicion based on identified risk factors may assist in more rapid diagnosis of this life-threatening mycosis.     

Film models for multicomponent mass transfer; computational methods: the exact solution of the maxwell-stefan equations

Computational difficulties which have been encountered in using the Krishna—Standart method for calculation of interphase mass transfer rates in multicomponent mixtures are discussed. Consideration is given to various alternative methods of performing the matrix calculations involved and to the stability of such methods. On this basis a computer algorithm is developed which is faster and more reliable than that published previously.