The making of a spam zombie army. Dissecting the Sobig worms

On 25 June 2003, a new mass-mailing worm, Sobig.E, emerged. The worm was highly successful at infecting computer systems. It is the fifth revision of a worm that first raised its ugly head in January 2003. There is strong evidence that spammers use infected computers to relay unsolicited commercial e-mail.     

Consumer knowledge of foodborne microbial hazards and food-handling practices.

A national telephone survey was conducted of 1,620 randomly selected U.S. residents who spoke English, were at least 18 years old, and resided in households with kitchen facilities. Respondents were interviewed about their recognition of foodborne pathogens, foods at risk for transmitting infection, knowledge of safe food handling, and food-handling practices. One-third of the respondents who prepared meals reported unsafe food hygiene practices: e.g., they did not wash hands or take precautions to prevent cross-contamination from raw meat. Unsafe practices were reported more often by men, adults 18 to 29 years of age, and occasional food preparers than by women, persons 30 years old or older, and frequent food preparers. Respondents who identified a food vehicle for Salmonella spp. were more likely to report washing their hands and cleaning cutting boards after preparing raw meat and poultry. The results raise concerns about consumer food-handling practices. The influence of food safety training, food-handling experience, and age on food-handling practices should be studied further. Awareness of a food vehicle for Salmonella spp., for example, may indicate knowledge of the etiology of foodborne disease that promotes safe food handling. Understanding the factors associated with safe food handling will assist in development of effective safe-food instruction programs.     

A cholera toxin-sensitive guanyl nucleotide binding protein mediates the movement of pituitary luteinizing hormone into a releasable pool: loss of this event is associated with the onset of homologous desensitization to gonadotropin-releasing hormone

Cholera toxin (CTX; 5 micrograms/ml), but not pertussis toxin (100 ng/ml), when preincubated with pituitary cells for 18 h, enhances the percentage of cellular LH released in response to continuous or pulsatile administration of 5 x 10(-9) M GnRH. This effect occurs without increasing total (intracellular plus extracellular) LH, indicating that it is best explained by redistribution of LH from a nonreleasable to a releasable pool. This site of action is consistent with the observation that CTX-pretreated cells are also sensitized to stimulation of LH release by the Ca2+ ionophore A23187. The observations that CTX stimulates the production of cAMP in these cells and that the sensitizing action of CTX is mimicked by (Bu)2cAMP (1 mM) are consistent with the view that a CTX-stimulated guanyl nucleotide binding protein, capable of activating adenylyl cyclase, is mediating this sensitization. We used a perifused cell system to show that the movement of LH into a releasable pool is lost with the onset of homologous desensitization due to high pulse frequency or constant administration of GnRH (5 x 10(-9) M, continuous or a pulse each 15 min). Sensitization to CTX is restored by stimulation with a high concentration of GnRH (10(-6) M) or by resetting the pulse frequency to the rate measured in vivo (a pulse each 90 min). Both of these treatments also circumvent the desensitized state, restoring LH release. These results identify a novel lesion associated with the development of desensitization in the gonadotrope and support the role of a CTX-sensitive guanyl nucleotide binding protein in regulation of pituitary responsiveness to GnRH.     

Rapid infusion system for neurosurgical treatment of massive intraoperative hemorrhage

Using an illustrative case of severe closed head injury that resulted in a posterior fossa epidural hematoma (EDH) and supratentorial epidural/subdural hematomas (SDH), the massive blood losses associated with operative repair of the torn sigmoid sinus and the significant fluid losses associated with refractory diabetes insipidus were treated by the intraoperative use of the Rapid Infusion System (RIS, Haemonetics). The RIS can rapidly infuse warm blood, crystalloid, or colloid at rates up to 1.5 L/min, thereby limiting the commonly associated hypotension, hypothermia, and coagulopathies. During the suboccipital craniectomy for evacuation of the EDH and repair of the sigmoid sinus, the patient required 18 units of blood replacement secondary to a large tear in the sigmoid sinus. During a separate craniotomy for evacuation of the SDH, the patient also developed diabetes insipidus, which increased the operative fluid replacement to 39 L. Despite these massive blood and fluid losses, the RIS limited the hypotension to less than 2 min and prevented hypothermia and the frequently associated coagulopathies. When used in a neurosurgical setting associated with massive blood and/or fluid losses, the RIS accomplishes three important objectives: (1) rapid infusion of intravenous fluids for maintaining perfusion pressure, (2) rapid warming of fluids despite high intravenous infusion rates of cold crystalloids, thereby preventing intraoperative hypothermia, and (3) continuous monitoring of infusion rates and totals.     

Glucagon-like peptide I enhances the insulinotropic effect of glibenclamide in NIDDM patients and in the perfused rat pancreas

OBJECTIVE: To investigate the acute effects of glibenclamide and glucagon-like peptide I (GLP-I) and their combination in perfused isolated rat pancreas and in patients with secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS: Rat islets were perfused with 10 nmol/l GLP-I in combination with 2 mumol/l glibenclamide. In human experiments, GLP-I (0.75 pmol. kg-1.min-1) was given as a continuous infusion during 240 min, while glibenclamide (3.5 mg) was administered orally. Eight patients participated in the study (age 57.6 +/- 2.7 years, BMI 28.7 +/- 1.5 kg/m2, mean +/- SE). In all subjects, blood glucose was first normalized by insulin infusion administered by an artificial pancreas (Biostator). RESULTS: GLP-I increased the insulinotropic effect of glibenclamide fourfold in the perfused rat pancreas. In human experiments, treatment with GLP-I alone and in combination with glibenclamide significantly decreased basal glucose levels (5.1 +/- 0.4 and 4.5 +/- 0.1 vs. 6.0 +/- 0.3 mmol/l, P < 0.01), while with only glibenclamide, glucose concentrations remained unchanged. GLP-I markedly decreased total integrated glucose response to the meal (353 +/- 60 vs. 724 +/- 91 mmol.l-1. min-1, area under the curve [AUC] [-30-180 min], P < 0.02), whereas glibenclamide had no effect (598 +/- 101 mmol.l-1. min-1, AUC [-30-180 min], NS). The combined treatment further enhanced the glucose lowering effect of GLP-I (138 +/- 24 mmol. l-1.min, AUC [-30-180 min], P < 0.001). GLP-I, glibenclamide, and combined treat-stimulated meal-induced insulin release as reflected by insulinogenic indexes (control 1.44 +/- 0.4; GLP-I 6.3 +/- 1.6, P < 0.01; glibenclamide 6.8 +/- 2.1, P < 0.01; combination 20.7 +/- 5.0, P < 0.001). GLP-I inhibited basal but not postprandial glucagon responses. Using paracetamol as a marker for gastric emptying rate of the test meal, treatment with GLP-I decreased gastric emptying at 180 min by approximately 50% compared with the control subjects (P < 0.01). CONCLUSIONS: In acute experiments on overweight patients with NIDDM, GLP-I exerted a marked antidiabetogenic action on the basal and postprandial state. The peptide stimulated insulin, suppressed basal glucagon release, and prolonged gastric emptying. The glucose-lowering effect of GLP-I was further enhanced by glibenclamide. This action may be at least partially accounted for by a synergistic effect of these two compounds on insulin release. Glibenclamide per se enhanced postprandial but not basal insulin release and exerted a less pronounced antidiabetogenic effect compared with GLP-I.     

Desire and efforts to quit smoking among cigarette smokers in Wisconsin

This research studied the desire and attempts of cigarette smokers in Wisconsin to quit smoking. Data were based on the 1993 Wisconsin Division of Health's Behavioral Risk Factor Surveillance System (BRFSS). Among the 23% of respondents who were current smokers, 79% said they wanted to quit smoking and 60% said they had quit smoking for a day or more in the preceding year. High rates of wanting to quit and having tried to quit were found in all demographic subgroups of smokers studied. Compared to lighter smokers, heavy cigarette smokers (20 or more cigarettes per day) were less likely to have tried quitting in the past year, but were almost as likely to want to quit. These results demonstrate the great demand for smoking cessation services among smokers in Wisconsin and support for efforts to increase the use and effectiveness of these interventions.     

Three-dimensional anatomical model-based segmentation of MR brainimages through principal axes registration

Model-based segmentation and analysis of brain images depends on anatomical knowledge which may be derived from conventional atlases. Classical anatomical atlases are based on the rigid spatial distribution provided by a single cadaver. Their use to segment internal anatomical brain structures in a high-resolution MR brain image does not provide any knowledge about the subject variability, and therefore they are not very efficient in analysis. The authors present a method to develop three-dimensional computerized composite models of brain structures to build a computerized anatomical atlas. The composite models are developed using the real MR brain images of human subjects which are registered through the principal axes transformation. The composite models provide probabilistic spatial distributions, which represent the variability of brain structures and can be easily updated for additional subjects. The authors demonstrate the use of such a composite model of ventricular structure to help segmentation of the ventricles and cerebrospinal fluid of MR brain images. Here, a composite model of ventricles using a set of 22 human subjects is developed and used in a model-based segmentation of ventricles, sulci, and white matter lesions. To illustrate the clinical usefulness, automatic volumetric measurements on ventricular size and cortical atrophy for an additional eight alcoholics and 10 normal subjects were made. The volumetric quantitative results indicated regional brain atrophy in chronic alcoholics     

Production of the 19-kDa antigen of Mycobacterium tuberculosis in Escherichia coli and its purification

The 19-kDa antigen (19Ag) of Mycobacterium tuberculosis (Mt) is a lipoprotein which is released from the organism during growth. In order to study the possible involvement of this antigen in the host protective response against Mt infection, it would be helpful to obtain high-level production of 19Ag from a recombinant organism. We have found that overexpression of the native 19Ag gene in Escherichia coli or yeast leads to products which are aggregated and insoluble. By site-directed mutagenesis of the 19Ag lipoprotein leader sequence, we have generated a mutant gene which directs the production of 19Ag into the periplasmic space of E. coli, from where it can be easily purified in high yield. 19Ag obtained from this mutant construct lacks the lipid-modified N-terminal Cys residue found in the native 19Ag, and is not glycosylated, but is otherwise indistinguishable from 19Ag isolated from Mt culture supernatant.