The composition of individual molecular species of plasma phosphatidylcholine in human pregnancy

The role of medical informatics in telemedicine is dependent on using the power of the computerized database to not only feed patient specific information to the health care providers, but to use the epidemiological and statistical information in the data base to improve decision making and ultimately care. The computer is also a powerful tool to facilitate standardizing and monitoring of care and when applied in continuous quality improvement methodology it can enhance the improvement process well beyond what can be done by hand. The coupling of medical informatics with telemedicine allows sophisticated medical informatics systems to be applied in low population density and remote areas.     

Dosing of aminoglycosides to rapidly attain pharmacodynamic goals and hasten therapeutic response by using individualized pharmacokinetic monitoring of patients with pneumonia caused by gram-negative organisms

Achieving a peak aminoglycoside concentration (Cmax)/MIC of > or = 10 within 48 h of initiation of therapy for pneumonia caused by gram-negative organisms results in a 90% probability of therapeutic response by day 7. Targeting an MIC of 1 microgram/ml, empirical aminoglycoside loading doses of 348 (25th- to 75th-percentile range, 275 to 432) mg were calculated to obtain a Cmax/MIC of 10 in our patient population. Individualized pharmacokinetic monitoring coupled with MIC data should determine subsequent dosing regimens to minimize the potential for toxicity and maximize the probability of clinical response.     

Interleukin 1 beta synergises with interleukin 2 in the outgrowth of autologous tumour-reactive CD8+ effectors

Using peritoneal fluid or pleural effusion obtained from 20 patients with lung, ovarian or metastatic breast cancer, we separated tumour cells from malignant effusion-associated mononuclear cells (MEMNCs) using discontinuous Ficoll-Hypaque density gradients. CD3+ T lymphocytes represented the main population of MEMNCs. The mean +/- s.d. CD4/CD8 ratio of MEMNC suspensions was 1.18 +/- 0.40. MEMNCs proliferated and expanded in vitro with human interleukin 2 (IL-2) either as CD3+ CD8+ cells or as CD3+ CD4+ cells or as mixed populations of CD8+ and CD4+ cells. Preferential cytolytic activity against autologous tumour cells was demonstrated in IL-2-activated MEMNC cultures with excess CD3+ CD8+ cells. In contrast, effectors derived from IL-2-activated cultures with excess CD3+ CD4+ cells lysed both autologous and allogeneic tumour target cells. The addition on day 0 of interleukin 1 beta (IL-1 beta) to MEMNCs cultured in the presence of IL-2 was effective in promoting the growth of CD3+ CD8+ cells and augmenting the cytotoxicity against autologous tumour. Simultaneously, the production of gamma-interferon (IFN-gamma) was increased in these cultures. This is the first report suggesting that IL-1 beta synergises with IL-2 to induce autologous tumour-specific CD8+ cytotoxic T lymphocytes (CTLs) within the MEMNC population. Selective enrichment in T-cell subsets by IL-1 beta may be useful in cellular adoptive immunotherapy using cells isolated from malignant effusions.     

DUB-1, a deubiquitinating enzyme with growth-suppressing activity

Cytokines regulate cell growth by inducing the expression of specific target genes. Using the differential display method, we have cloned a cytokine-inducible immediate early gene, DUB-1 (for deubiquitinating enzyme). DUB-1 is related to members of the UBP superfamily of deubiquitinating enzymes, which includes the oncoprotein Tre-2. A glutathione S-transferase-DUB-1 fusion protein cleaved ubiquitin from a ubiquitin-beta-galactosidase protein. When a conserved cysteine residue of DUB-1, required for ubiquitin-specific thiol protease activity, was mutated to serine (C60S), deubiquitinating activity was abolished. Continuous expression of DUB-1 from a steroid-inducible promoter induced growth arrest in the G1 phase of the cell cycle. Cells arrested by DUB-1 expression remained viable and resumed proliferation upon steroid withdrawal. Our results suggest that DUB-1 regulates cellular growth by modulating either the ubiquitin-dependent proteolysis or the ubiquitination state of an unknown growth regulatory factor(s).     

Epoxidation of olefins by cytochrome P450: evidence from site-specific mutagenesis for hydroperoxo-iron as an electrophilic oxidant

P450 cytochromes (P450) catalyze many types of oxidative reactions, including the conversion of olefinic substrates to epoxides by oxygen insertion. In some instances epoxidation leads to the formation of products of physiological importance from naturally occurring substrates, such as arachidonic acid, and to the toxicity, carcinogenicity, or teratogenicity of foreign compounds, including drugs. In the present mechanistic study, the rates of oxidation of model olefins were determined with N-terminal-truncated P450s 2B4 and 2E1 and their respective mutants in which the threonine believed to facilitate proton delivery to the active site was replaced by alanine. Styrene epoxidation, cyclohexene epoxidation and hydroxylation to give 1-cyclohexene-3-ol, and cis- or trans-butene epoxidation (without isomerization) and hydroxylation to give 2-butene-1-ol were all significantly decreased by the 2B4 T302A mutation. Reduced proton delivery in this mutant is believed to interfere with the activation of dioxygen to the oxenoid species, as shown earlier by decreased hydroxylation of several substrates and enhanced aldehyde deformylation via a presumed peroxo intermediate. Of particular interest, however, the T303A mutation of P450 2E1 resulted in enhanced epoxidation of all of the model olefins along with decreased allylic hydroxylation of cyclohexene and butene. These results and a comparison of the ratios of the rates of epoxidation and hydroxylation support the concept that two different species with electrophilic properties, hydroperoxo-iron (FeO2H)3+ and oxenoid-iron (FeO)3+, can effect olefin epoxidation. The ability of cytochrome P450 to use several different active oxidants generated from molecular oxygen may help account for the broad reaction specificity and variety of products formed by this versatile catalyst.     

Guide to epidemiological surveillance for rinderpest. Office International des Epizooties

The practical implementation of epidemiological surveillance programmes for rinderpest prescribed by the standards of the Office International des Epizooties (OIE) is described. The rationale of surveillance is discussed in relation to the stages of disease control, discontinuation of vaccination, clinical surveillance and serological surveillance. These stages lead to provisional and confirmed declarations of freedom from disease, and the confirmed declaration of freedom from infection. Practical methods of stratification of livestock populations, and selection of samples of herds and animals within selected herds are explained. The actions to follow any discovery of disease, or any clinical or serological signs of disease, are discussed. In the serological surveillance stage, balancing the number of herds and the number of animals within selected herds tested can result in considerable reduction in the overall number of serum samples to be tested. The methods used in rinderpest surveillance can readily be adapted to surveillance programmes for other diseases.     

Subchronic oral hepatotoxicity of turmeric in mice--histopathological and ultrastructural studies

OBJECTIVE: To analyze the effects of flutamide in patients with physical and/or mental disorders consulting for urinary symptoms secondary to benign prostatic hyperplasia (BPH). METHODS: 50 patients with BPH in whom surgical treatment was contraindicated due to their physical and/or mental condition were treated with flutamide 250 mg/day. Four patients presented with urinary retention and 46 patients had prostatic symptomatology. Patients were evaluated using the symptoms score (I-PSS) and quality of life (QL). Prostate volume was measured by transabdominal US; the maximum flow rate at spontaneous micturition and residual urine were determined. RESULTS: At 12 months, the I-PSS and QL scores decreased by a mean of 7 and 3 points, respectively. The US demonstrated that treatment had reduced prostatic volume by a mean of 10 gms. The maximum flow rate at spontaneous micturition increased 3 ml/sec and residual urine decreased by 15 ml. CONCLUSION: Flutamide is another alternative to surgery in specific patients with BPH.     

Molecular and functional characterization of a calcium-sensitive chloride channel from mouse lung

A protein (mCLCA1) has been cloned from a mouse lung cDNA library that bears strong sequence homology with the recently described bovine tracheal, Ca2+-sensitive chloride channel protein (bCLCA1), bovine lung endothelial cell adhesion molecule-1 (Lu-ECAM-1), and the human intestinal Ca2+-sensitive chloride channel protein (hCLCA1). In vitro, its 3.1-kilobase message translates into a 100-kDa protein that can be glycosylated to an approximately 125-kDa product. SDS-polyacrylamide gel electrophoresis from lysates of mCLCA1 cDNA-transfected transformed human embryonic kidney cells (HEK293) reveals proteins of 130, 125, and 90 kDa as well as a protein triplet in the 32-38 kDa size range. Western analyses with antisera raised against Lu-ECAM-1 peptides show that the N-terminal region of the predicted open reading frame is present only in the larger size proteins (i.e. 130, 125, and 90 kDa), whereas the C-terminal region of the open reading frame is observed in the 32-38 kDa size proteins, suggesting a posttranslational, proteolytic processing of a precursor protein (125/130 kDa) into 90 kDa and 32-38 kDa components similar to that reported for Lu-ECAM-1. Hydrophobicity analyses predict four transmembrane domains for the 90-kDa protein. The mCLCA1 mRNA is readily detected by Northern analysis and by in situ hybridization in the respiratory epithelia of trachea and bronchi. Transient expression of mCLCA1 in HEK293 cells was associated with an increase in whole cell Cl- current that could be activated by Ca2+ and ionomycin and inhibited by 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid, dithiothreitol, and niflumic acid. The discovery of mCLCA1 opens the door for further investigating the possible contribution of a Ca2+-sensitive chloride conductance to the pathogenesis of cystic fibrosis.     

Racial differences in women's desires to be thin

The goal of this research was to attempt to understand why white women are more prone to develop eating disorders than black women. Using self-reports, we found that white women chose a significantly thinner ideal body size than did black women, and expressed more concern than black women with weight and dieting. White women also experienced greater social pressure to be thin than did black women. White men indicated less desire than black men to date a women with a heavier than ideal body size, and white men felt they would more likely be ridiculed than did black men if they did date a woman who was larger than the ideal. The results suggest that black women experience eating disorders less than white women at least in part because they experience less pressure to be thin.