'98 Escherichia coli SWISS-2DPAGE database update

The combination of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), computer image analysis and several protein identification techniques allowed the Escherichia coli SWISS-2DPAGE database to be established. This is part of the ExPASy molecular biology server accessible through the WWW at the URL address http://www.expasy.ch/ch2d/ch2d-top.html . Here we report recent progress in the development of the E. coli SWISS-2DPAGE database. Proteins were separated with immobilized pH gradients in the first dimension and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension. To increase the resolution of the separation and thus the number of identified proteins, a variety of wide and narrow range immobilized pH gradients were used in the first dimension. Micropreparative gels were electroblotted onto polyvinylidene difluoride membranes and spots were visualized by amido black staining. Protein identification techniques such as amino acid composition analysis, gel comparison and microsequencing were used, as well as a recently described Edman "sequence tag" approach. Some of the above identification techniques were coupled with database searching tools. Currently 231 polypeptides are identified on the E. coli SWISS-2DPAGE map: 64 have been identified by N-terminal microsequencing, 39 by amino acid composition, and 82 by sequence tag. Of 153 proteins putatively identified by gel comparison, 65 have been confirmed. Many proteins have been identified using more than one technique. Faster progress in the E. coli proteome project will now be possible with advances in biochemical methodology and with the completion of the entire E. coli genome.     

Do cardiovascular risk factors explain the relation between socioeconomic status, risk of all-cause mortality, cardiovascular mortality, and acute myocardial infarction?

Much remains to be understood about how low socioeconomic status (SES) increases cardiovascular disease and mortality risk. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (1984-1993) were used to estimate the associations between acute myocardial infarction and income, all-cause mortality, and cardiovascular mortality in a population-based sample of 2,272 Finnish men, with adjustment for 23 biologic, behavioral, psychologic, and social risk factors. Compared with the highest income quintile, those in the bottom quintile had age-adjusted relative hazards of 3.14 (95% confidence interval (CI) 1.77-5.56), 2.66 (95% CI 1.25-5.66), and 4.34 (95% CI 1.95-9.66) for all-cause mortality, cardiovascular mortality, and AMI, respectively. After adjustment for risk factors, the relative hazards for the same comparisons were 1.32 (95% CI 0.70-2.49), 0.70 (95% CI 0.29-1.69), and 2.83 (95% CI 1.14-7.00). In the lowest income quintile, adjustment for risk factors reduced the excess relative risk of all-cause mortality by 85%, that of cardiovascular mortality by 118%, and that of acute myocardial infarction by 45%. These data show how the association between SES and cardiovascular mortality and all-cause mortality is mediated by known risk factor pathways, but full "explanations" for these associations will need to encompass why these biologic, behavioral, psychologic, and social risk factors are differentially distributed by SES.     

Heroin related overdose problems

During the first ten months of 1992 the Oslo Ambulance Department registered 716 incidences of assumed drug-related intoxications. 80% happened in down town Oslo. 19 cases of asystoly were recorded, 13 of the patients recovered after treatment, without sequelae. Five of these patients left the location after emergency help and they refused hospitalization. 432 of the patients were unconscious when the ambulance personal arrived, 472 were treated with naloxone both by the intramuscular and the intravenous route. Most of the persons refused further observation. A team of specially trained out reach workers offers help after acute medical treatment by means of "streetwork". The intervention is directed at addicts who have experienced an overdose.     

Application of polymerase chain reaction for the correlation of Salmonella serovars recovered from greyhound feces with their diet

The polymerase chain reaction was employed to correlate Salmonella serovars isolated from fecal material of greyhounds suffering from gastroenteritis with those isolated from the diet fed to the greyhounds prior to onset of diarrhea. Kennels around the Abilene, Kansas, area were contacted and supplied with materials needed to collect a portion of the diet each day. With the onset of diarrhea, the kennels were instructed to ship the fecal material and diet from the previous 10 days to the laboratory for testing. Forty-one fecal samples and corresponding diets were screened for Salmonella, Clostridium perfringens, Campylobacter jejuni, Staphylococcus aureus, Staphylococcus intermedius, and pathogenic (piliated) Escherichia coli by direct culture using standard procedures. The fecal material was also screened for coronavirus and parvovirus using electron microscopy. Thirty-five "normal" fecal samples were screened for all of the above mentioned microorganisms as a control. In addition, the fecal material was screened for E. coli verotoxins I and II and clostridial enterotoxins. A total of 61 Salmonella isolates were recovered from the 41 samples of feces and diet submitted for testing; 31 were recovered from the feces and 30 from the diet. Four Salmonella isolates were recovered from the normal fecal samples. Results obtained by PCR, plasmid profiles, antigenic analysis, and antibiogram profiles indicated that 16 of the 31 isolates recovered from the fecal material were the same strain as that recovered from the diet.     

Acute effect of inorganic iodide after 131I therapy for hyperthyroidism

Patients treated with inorganic iodide weeks to years following 131I therapy for hyperthyroidism do not adapt to its antithyroid effect. To determine whether such adaptation occurs soon after 131I therapy, serum thyroxine (T4) and triiodothyronine (T3) concentrations were measured daily for 9-14 days following 131I therapy in seventeen hyperthyroid patients. Nine patients received 150 mg KI daily starting 48 h after 131I administration; eight received only 131I. Serum T4 and T3 concentrations did not change significantly in the patients who received only 131I. In the patients who received 131I and KI, serum T4 and T3 concentrations fell promptly, reaching nadir values 2-10 days after initiation of iodide, and then increased despite continuation of KI therapy. The mean maximal fall in serum T4 was 34% and in serum T3 42%. These results show that "escape" from the acute anti-thyroid effect of iodide occurs when it is given immediately after 131I therapy, thus limiting the utility of iodide as a therapeutic agent at this time.     

Creatine kinase isoenzymes in serum from cord blood and the blood of healthy full-term infants during the first three postnatal days

Isoenzymes of creatine kinase (ATP:creatine phosphotransferase; EC 2.7.3.2; CK) were measured by electrophoresis in serum from cord blood and skin-puncture blood taken from 45 healthy full-term infants during the first three postnatal days. Mean total CK activities (in U/L at 30 degrees C) were 185 in cord samples, 536 in samples taken between 5--8 h postnatally, 494 between 24--33 h, and 288 in the 72-100 h samples. Values for all three isoenzymes increased to a peak over this period, with the highest values generally being found in the samples taken 5--33 h after birth; the subsequent decline was most rapid for CK-BB. Serum CK isoenzymes in cord samples and those taken at 72--100 h in the 11 babies delivered by cesarian section did not differ significantly from those of babies delivered vaginally. However the postnatal increases in total CK, CK-MM, and CK-MB (but not in CK-BB) were significantly greater in those patients born by vaginal delivery. The reasons for the increases in CK isoenzymes after birth are not clear, but our results and reported studies on the ontogeny of CK suggest that CK-MB cannot be regarded as a "cardiac-specific" isoenzyme in the neonatal period.     

Inhibition of feline collateral vessel development following experimental thrombolic occlusion

We compared development of feline hindlimb collateral circulation after acute occlusion of the terminal aorta by ligation, thrombus formation, and formation of a "closed" aortic loop containing thromboplastin. Collateral circulation development was assessed by aortograms, scintillation scans, neurological signs following occlusion, measurement of hindlimb muscle blood flow, and forelimb and hindlimb temperature. In cats in which aortic occlusion was the result of ligation or thromboplastin in the aortic loop, paralysis was not evident. Aortograms and scintillation scans indicated hindlimb blood flow. Both muscle temperature and blood flow data indicated that the return of blood flow was rapid. The 5th lumbar artery appears to be the origin of the collateral vessels. The mid-zone component is a dorsal and ventral vertebral route and an epaxial muscle route. The reentry components are the 6th or 7th lumbar arteries. The collateral vessels arise from preexisting collateral vessels. Of those cats in which aortic occlusion was the result of a thrombus, all exhibited paralysis. Aortograms, scintillation scans, muscle temperature, and hindlimb blood flow data indicated reduced hindlimb blood flow. The results suggest that the thrombus has an inhibitory effect on the development of collateral circulation.     

Changes in serum thyrotropin (TSH) in man during halofenate administration

Halofenate, a serum lipid-lowering agent which inhibits binding of thyroid hormone to thyroxine-binding globulin (TBG), was administered daily for 14 days to 8 hypothyroid subjects with elevated TSH concentrations as a result of incomplete thyroxine (T4) therapy. Drug administration resulted in mean increases in serum dialyzable fraction T4 (DFT4) of 52% over pretreatment levels (P less than 0.01) and in dialyzable fraction triiodothyronine (DFT3) of 26% in 7 subjects, (P less than 0.01). During halofenate treatment in these 7 subjects, serum TSH concentrations decreased significantly (mean = 39%, P less than 0.01) when DFT4 and DFT3 were increased by halofenate. In only two subjects was there a convincing temporal relationship between increased serum absolute free T4 (AFT4) and decreased serum TSH concentrations. Contrary to what would be predicted from the "free hormone hypothesis", changes in serum TSH concentration in these hypothyroid patients appeared to relate primarily to changes in the free fraction of circulating T4 and T3 (DFT4, DFT3), rather than to alterations in AFT4 or AFT3. Halofenate did not alter serum TBG binding capacity. An eighth subject did not show increased DFT4 and DFT3 during halofenate treatment despite achievement of therapeutic serum levels of the agent; in this patient, serum TSH levels rose progressively throughout the period of inadequate T4 replacement and halofenate administration. In hypothyroid patients, short-term halofenate use suggests that the pituitary-thyroid hormone feedback circuit can respond to increases in serum DFT4 and DFT3 in the absence of detactable increases in absolute free hormone concentrations.     

Distributed computing for multidisciplinary design optimization using Java

The programming language Java (recently referred to as the computer language of the Web) offers substantial possibilities for the type of complex engineering problems typically encountered in multidisciplinary design optimization (MDO) problems. In order to demonstrate the potential uses of Java for MDO problems, this paper presents the development of the Web Interface for complex engineering design (WICkED) software, which simulates the convergence of a decomposed complex system in a distributed computing environment and computes the sensitivity derivatives of the system with respect to the independent input variables using the GSE method or the finite difference method. In this application, one computer is designated as the server and sends out required inputs to a number of client subsystems over the Internet. A number of client computers can connect to the server and then receive the inputs necessary to calculate the solution to their model. As the code necessary to solve the model already exists at the client, only the inputs have to be sent over the network. When the client has solved the calculation, it returns the results to the server which processes the result to produce new inputs.WICkED is written entirely in the Java programming language which allows server and clients to exist on completely different computer types and in heterogeneous, distributed networks. A number of parametric studies on the behaviour of complex systems in a distributed environment are performed and the results are reported in this paper. This research serves to identify potential problems as well as advantages in using Java for MDO applications.     

Susceptibility to tropical theileriosis of calves born to dams immunized with Theileria annulata (Hisar) cell culture vaccine

Epidemiological evidence suggests that millet might play a role in the etiology of endemic goiter. Recently, we showed that a traditional fermentation procedure of two pearl millet (Pennisetum americanum L. Lecke) cultivars grown in Sudan modified their effects on the weight of the thyroid gland and thyroid hormone profile in rats. In the present study, we report that this fermentation procedure reduced the ash contents of millet by about 40% and removed considerable amounts of Mg (>50%), Zn (27-39%) and K (45%). Other minerals (Ca, Fe, Cu) were not affected. Feeding of one fermented cultivar resulted in significant reduction in bone Mg and Zn contents, whereas feeding of the other fermented cultivar resulted in reduction of bone Mg only. Dietary Mg intake and bone Mg contents correlated negatively with serum T3. Groups fed the millet diets had higher serum Se level compared to those fed wheat or casein diets and feeding of fermented millet resulted in a further increase in serum Se level. Thus our data indicate that in rats the enhanced effects of millet on the thyroid induced by fermentation is likely related to removal of minerals from millet and/or chemical transformation of the goitrogens contained in millet.