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J Wilde

Publications and source records attributed to J Wilde.

At least 37 records · Page 2Linked to original sources

Eye movements in baboons performing a matching-to-sample task presented in a divided-field format.

We examined eye saccades in a baboon solving a video-formatted matching-to-sample (MTS) task. In that task, the animal had to place a cursor by way of joystick manipulation within the boundaries of a fixation point (FP) displayed on a monitor. A sample stimulus was then flashed in either the left or right of FP. Immediately thereafter, two comparison forms were displayed and the animal had to select the comparison form matching the sample. A new video technique requiring no specific head or body constraints was employed to monitor eye movements. Expt. 1 indicated that the gaze was centered on FP during the fixation procedure. However, some goal-directed express saccades, with mean latencies of 100 ms, were observed during sample presentation. Expt. 2 used an overlap procedure in which FP remained visible during sample presentation. Latencies of express saccades increased by approximatively 20 ms. Expt. 3 showed in four baboons that the overlap procedure did not affect scores. It is concluded that the computerized MTS task is a valuable tool for the assessment of hemispheric lateralization in visual processing in intact primates, as long as the sample is not displayed longer than 120 ms.

Animals↗

Substrate and inhibitor specificity of mevalonate kinase determined with substrate analogues.

Substrate analogues of mevalonate kinase were prepared and their kinetic properties determined with the enzyme from pig liver. The analogues are derived from mevalonate by substitutions of hydroxyl and/or methyl at C3(group 1), by systematic prolongation of C6 to yield 3-alkyl-3,5-dihydroxyvalerates (group 2) and by methylation at C2, C6 and C4 (group 3). Compounds of group 1 were inhibitors of mevalonate kinase, their Ki values ranging over 140 mM to 2.5 mM and decreasing in the series CH2 > C(CH3)2 > CH(OH) > CH(CH3) > C(OH)-CO2H > C(OH)CH2OH. Three of these analogues, the competitive inhibitors 3,5-dihydroxyvalerate, 3-methyl-5-hydroxy-valerate and 3,3-dimethyl-5-hydroxyvalerate are alos (poor) substrates of the kinase. Substances of group 2 contain an additional hydrophobic group and are noncompetitive inhibitors with Ki values decreasing systematically from 7.7 mM to 0.7 mM in the sequence 3-n-propyl, 3-n-butyl, 3-n-pentyl and 3-n-hexyl derivative of 3,5-dihydroxyvalerate. The methylated mevalonates of group 3 are competitive inhibitors as well as good substrates of the kinase, their Ki = Km values ranging over 4.3-0.2 mM and their maximal velocities related to mevalonate varying between 7-65%. All of these analogues have in common the carbon chain and 5-hydroxy group of the substrate and could, therefore, fit to the active site of mevalonate kinase and be phosphorylated by ATP. The results, however, indicate a strong dependence of such interaction on the ligands at C3 of the substrate. Enzymic activity as well as affinity are lost if both of these ligands are replaced by hydrogen; partial restoration occurs at a low level if only one of the ligands is concerned. In the presence of the ligands even monomethylation at C2 and C4 yields enzymically active products. Oxidation of C6 of the substrate yields inhibitors but methylation yields a reasonably good substrate. Thus 3,5-dihydroxy-3-ethylvalerate fits into the active site whereas higher C6 homologues are only inhibitory and probably bind to a hydrophobic region of the enzyme. Some of these results are shown to have parallels in the enzymic behaviour of fluorinated mevalonates.

Adenosine Triphosphate↗

Office identity.

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Attitude of Health Personnel↗

Detection of rotaviruses in the day care environment by reverse transcriptase polymerase chain reaction.

Group A rotavirus is an important cause of morbidity among infants and toddlers in day care centers. Transmission by the fecal-oral route is well established, but fomites and environmental surfaces may also play an important role in transmission. A highly sensitive polymerase chain reaction (PCR) assay was used to detect rotavirus RNA in day care environments. Areas sampled included floors, diaper change areas, toy balls, and other surfaces. In two centers undergoing outbreaks of rotavirus, 7 (39%) of 18 toy balls had detectable rotavirus as did 8 (21%) of 39 swabs from environmental surfaces. By comparison, only 1 (5%) of 21 toy balls and 1 (2%) of 44 environmental surface swabs had detectable rotavirus in centers without rotavirus outbreaks (P = .0001). Thus, rotaviruses are highly prevalent in day care centers during outbreaks of diarrhea. The monitoring of environments by sensitive nucleic acid amplification techniques may lead to strategies for the diminution of disease transmission within the day care environment.

Base Sequence↗

Improved detection of rotavirus shedding by polymerase chain reaction.

To improve identification of children excreting rotavirus a method for the amplification of rotavirus RNA by the polymerase chain reaction (PCR) was developed. The assay was compared with a solid-phase enzyme immunoassay in the detection of rotavirus shedding by infants in hospital during the winter peak of rotavirus infections. Forty children were studied in an intermediate care unit after transfer from intensive care units. Only two were admitted primarily because of diarrhoea; the other thirty-eight were admitted for management of various other disorders. Rotavirus shedding was detected by enzyme immunoassay in twenty of the infants, and nine of these (aged 1 week to 8 months) remained in hospital for more than 5 days after the initial detection of rotavirus and could be studied long term. Of 103 faecal samples from the nine infants, 60 (58%) contained rotavirus RNA detected by reverse-transcriptase (RT)/PCR, whereas only 37 (36%) were positive for rotavirus antigen by the immunoassay (chi 2 = 10.3, p less than 0.002). The geometric mean time of rotavirus shedding was 9.5 (range 1-19) days as detected by RT/PCR and 5.7 (range 1-17) days by the immunoassay (p less than 0.018). In five of the nine children, RT/PCR detected rotavirus shedding for 2-7 days longer than the immunoassay and in four children RT/PCR was positive 1 or more days before rotavirus antigen was detected. Further studies should attempt to find out whether infected infants are capable of spreading wild-type virus during periods when they are not shedding antigen as detectable by enzyme immunoassay.

Antigens, Viral↗

Detection of animal and human group B rotaviruses in fecal specimens by polymerase chain reaction.

A combined reverse transcriptase reaction-polymerase chain reaction (RT-PCR) was developed to achieve the sensitive detection of group B rotaviruses (GBR). Sequences derived from genomic segment 3 of the IDIR (intestinal disease of infant rats) strain of GBR permitted the detection of greater than or equal to 0.08 pg of purified IDIR genomic RNA (4,000 genome copies). Primers complementary to the terminal sequences of gene 11 of GBR strain ADRV (adult diarrhea rotavirus) allowed for the detection of as little as 0.008 pg of purified ADRV genomic RNA. Detection of heterologous strains of GBR was also observed with these primer pairs. IDIR gene 3 primers recognized greater than or equal to 8 pg of RNA from bovine GBR obtained from a variety of geographic locations. RNA from IDIR, but not bovine GBR, strains was detected by means of RT-PCR with ADRV gene 11 primers. Neither set of GBR primers was reactive in RT-PCR with fecal specimens containing group A rotaviruses or fecal specimens from uninfected controls. This RT-PCR assay permits the sensitive and specific detection of a variety of GBR in fecal specimens.

Animals↗

Immunoglobulins and other modalities for the prevention and treatment of enteric viral infections.

Viral infections of the gastrointestinal tract constitute a major health problem during the first years of life. In addition to causing acute diarrhea, rotaviruses and other enteric viruses may be involved in the pathogenesis of necrotizing enterocolitis and other neonatal enteric diseases. There are several potential methods for the prevention and treatment of gastrointestinal viral infections. Antiviral immune globulins, administered by the parenteral or oral route, might prove useful for the inhibition of intestinal viral replication. Alternatively, specific glycoprotein inhibitors of viral-cell binding might be used to prevent the productive infection of intestinal epithelial cells. In addition, since many enteric viruses require proteolytic enzymes for protein cleavage, protease inhibitors may prove to be effective agents for the inhibition of intestinal viral replication. At this point in time, these methods have proven useful for the inhibition of rotavirus infection in experimental animals. The successful application of these and other methods for the prevention of enteric infections in humans might substantially reduce the morbidity and mortality associated with enteric diseases.

Animals↗

Removal of inhibitory substances from human fecal specimens for detection of group A rotaviruses by reverse transcriptase and polymerase chain reactions.

A method was developed for the purification of rotavirus RNA from fecal extracts in order to permit the sensitive identification of group A rotavirus in fecal specimens by the polymerase chain reaction. Sequential reactions with reverse transcriptase and Taq polymerase with directed primers from rotavirus gene 6 yielded characteristic 259-base-pair fragments that were then visualized by silver stain on a polyacrylamide gel. As few as 500 genomic copies of purified rotavirus RNA could be detected in this manner. However, when the method was applied to fecal samples with added rotavirus virions, inhibition was noted in many of the fecal extracts which were tested. The inhibition could be reversed by dilution of the fecal extract, but sensitivity was also reduced by a corresponding dilutional factor. The inhibition was quantitatively removed by an added step in the extraction process that utilized chromatographic cellulose fiber powder (CF11 powder) to purify the rotavirus RNA during a series of rapid washing and elution steps. After CF11 purification, rotavirus RNA could be detected in experimental fecal samples at dilutions 1,000- to 10,000-fold beyond the detection limits of standard techniques such as enzyme immunoassay and the direct visualization of RNA following polyacrylamide gel electrophoresis. Furthermore, following purification by CF11, rotavirus RNA could be detected in all of seven enzyme-linked immunosorbent assay-positive fecal samples obtained from a child with rotavirus gastroenteritis; when CF11 purification was not performed, rotavirus RNA could be detected in only four of these samples, even after the removal of inhibitors by dilution of the extracts. Large-scale identification of rotavirus in fecal specimens may be possible by use of CF11 purification of viral RNA prior to sequential reactions with reverse transcriptase and Taq polymerase in a modified polymerase chain reaction.

Feces↗

On the action of carboxy groups in the citrate synthase reaction.

The aza analogue (RS)-3-hydroxy-2,5-pyrrolidinedione-3-acetic acid (6) of the five-membered citric anhydride (2) was prepared in the sequence citric acid----2-phenyl-1,3-dioxolan-4-one-5,5-diacetic acid (1)----citric acid beta-amide (3)----6 and used to resolve ambiguities in the mechanism of the citrate synthase reaction. The results yield no indication for the formation of anhydride 2 on the enzyme and favour the direct hydrolysis of the intermediate (3S)-citryl-CoA. Ammonolysis of the dioxolanone 1 in the reaction sequence described above produced not only citric acid beta-amide but also the alpha-isomer. This is shown to originate in the transient formation of anhydride 2. Hydrolysis of the dioxolanone 1 under "physiological conditions" occurs via anhydride 2, generated in intramolecular bifunctional catalysis by a protonated and a deprotonated carboxyl group. The catalytic residue Asp375 of citrate synthase is considered to operate on the enzyme as does the protonated carboxyl group in the chemical reaction and to generate enolic acetyl-CoA in cooperative catalysis with His274. This reaction of Asp375 may also facilitate the hydrolysis of citryl-CoA.

ATP Citrate (pro-S)-Lyase↗

[Lung cancer in the DDR with special reference to histological types and cigarette consumption].

By an analysis in detail of incidences of lung cancer of the years 1971 to 1984 and of the data of consumption of cigarettes per head in GDR during the years 1960 to 1984 we discussed the further trends of morbidity and mortality in lung cancer in our country. We pointed out: 1. From 1972 to 1985 the mortality of lung cancer in males dropped from 6,023 per year to 5,213, while that of females increased from 698 to 959. 2. In the time from 1971 to 1983 the over-all incidence (crude rates) of lung cancer in males decreased from 87.1 per 100,000 to 75.5 per 100,000, but came up to 77.2 per 100,000 in 1984. The females rose from 9.7 to 12.3 per 100,000 in the same interval. 3. The age related incidences showed different courses not regarding the different levels of both sexes. In the age group of 30-59 we found a significant incidence rise. The incidence of the 60-69 year old males dropped in a range of 10%; that of the females with the same age had an undulating course with rising trend. Males and females of an age of 70 years and older also had an undulating course with increasing trend. 4. Between 1970 and 1979 the proportions of histological types moved. The adenocarcinomas of males rose significantly from 10.0 to 12.6% and that of large cell carcinomas from 3.6 to 6.0%. In the females the proportions of large cell cancers rose also from 4.2 to 7.5%. 5. The histological types of lung cancer have a significant age relation: Undifferentiated cancers and adenocarcinomas decrease with the age while proportions of squamous cell cancers rise with the age. 6. During 1960 to 1969 the market share of filter cigarettes changed from less than 10% to 79% and rose to 91% until 1975. In the same time the cigarette consumption per head of population increased continuously until now (1984: consumption of cigarettes per head 1,845). 7. In the age group of 18-25 the proportions of smokers is 50% and their middle consumption of cigarettes per day amounts to 11 cigarettes. In the age group of 45-55 the proportion of smokers runs to 34% and their cigarette consumption per day comes to 15 cigarettes. The proportion of male smokers amounts to 47%. The proportion of female smokers amounts to 18%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

[Epidemiologic aspects of the histologic types of lung cancer].

An epidemiological study was performed in the county of Erfurt including all lung cancer patients of the years 1963, 1968, and 1972 to 1977, together 2,585 males and 358 females. The following results were found: 1. The incidence of lung cancer increased significantly from 1963 to 1977. 2. About 60% of all lung cancer patients were younger than 70 years. 3. In male patients squamous cell carcinomas prevailed with 44.8%. Small cell cancers came up to 34.6% and adenocarcinomas to 10.1%. Large cell cancers reached 10.5%. These types in female patients had a proportion to each other like 26.9%: 30.8%: 30.4%: 11.9%. The proportion of adenocarcinomas increased significantly during 1963 to 1977. 4. We found a non significant age relation of histological types. The adenocarcinoma and the small cell cancers dropped with rising age. 5. The classification of histological types and the conditions of detection of lung cancers did not change in the study interval. Therefore the altering of patterns of histological types, especially the increase of adenocarcinomas was attached to the beginning of cigarette smoking in younger ages and the increasing proportion of filter tipped brands as well to a variation of exposition against professional cancerogens. 6. Patients with adenocarcinomas have the highest survival rate after 5 years: 8.1%. Squamous cell lung cancer patients have a 5 year survival rate of 6.8%. Patients with small cell cancers and large cell cancers ranged at 2.7% or 2.6%. 7. Peripheral tumors of each histological type will be detected earlier by fluorographic screening than central carcinomas. Therefore the 5 year survival rates of peripheral cancers always are more favourable than that of central cancers. 8. For the problems in exact typing and staging we propose an internationally adjusted definition of tumor localization as a third parameter for prognosis.

Adenocarcinoma↗

[The relationship of histological type and tumor location to prognosis in 1000 patients with lung resection with special reference to adenocarcinoma].

On the basis of clinical investigations of 1,000 resected lung cancer patients we comment on the prognostic implications of histological type and tumour localisation with special regard to adenocarcinoma. 1. 198 patients, resected for primary adenocarcinoma of the lung, had 5- and 10-year survival rates of 42% and 25.3% respectively, similar to the survival rate of patients who had been operated on for squamous cell carcinoma. 2. Of 6 patients suffering from central adenocarcinoma according to WHO classification of 1967, or 10 patients according to WHO classification of 1981, not a single patient survived for more than 3 years. In patients with peripheral adenocarcinoma the survival rates after 5 and 10 years amounted to 42.4% and 26.6%. The 5-year survival rates of all patients with peripheral cancers were significantly better than those of central tumour patients. 3. The survival rates after 5 and 10 years among patients resected for primary adenocarcinoma dropped steeply in relation to tumour stage. While adenocarcinoma patients in stage I had the highest survival chances in comparison to other types, the survival curve of stage III patients with this type fell below that of small-cell and large-cell cancer patients. 4. The prognosis of patients resected for adenocarcinoma whose x-ray pictures showed a large infiltration, had a bad prognosis. Patients with peripheral coin lesions had good survival chances. 5. It was impossible to demonstrate a correlation between survival rate and grade of differentiation in adenocarcinoma patients. There were also no prognostic differences between papillary and acinar subtype. Patients with bronchiolo-alveolar carcinoma had the significantly highest survival rates.

Adenocarcinoma↗

[Transitory bacteremia in bronchologic-biopsy procedures].

In 105 patients, the incidence of transitory bacteraemia seen following bronchological-bioptic interventions was investigated. In three patients (2.9%), the identical pathogens were detected both in the bronchial secretion and in venous blood culture following bronchoscopy.

Bacteria↗

Structural variability of the external glycoprotein of simian immunodeficiency virus propagated in cell cultures.

We examined the structural variability of the external glycoprotein (gp130) of a cloned simian immunodeficiency virus (SIV) in culture. Cloned SIVmac142 was either permanently propagated in HUT-78 cells or sequentially passaged in MT-2 cells. After 12, 24 and 60 passages of permanent or lytic cell-culture systems, virus was harvested, gp130 was isolated and peptide mapped. Comparison of gp130 peptide maps of SIVmac142 by computer graphic analysis revealed a variation in relative spot intensity of up to 20%. No major variability of gp130 was observed in SIVmac142 propagated in HUT-78 cells (i.e. without cytopathic effect induction) in up to 60 passages. However, in MT-2 cells, which are lysed by this virus, gp130 exhibited significant variability and displayed six additional fragments in peptide maps after 24 passages. Peptide map of SIVmac142 gp130 obtained after 60 passages in MT-2 cells was comparable to that after 24 passages. Alterations in the intensity of certain spots indicated changes in the composition of the replicating virus population.

Genetic Variation↗

A 10 year follow-up of semi-annual screening for early detection of lung cancer in the Erfurt County, GDR.

A prospective and controlled study for early detection of lung cancer in the county of Erfurt with a follow-up of 10 years is presented. A collective of 41,532 males born between 1907 and 1932 was screened by chest fluorography at 6 month intervals and compared with a control group consisting of 102,348 males of the same age, who were screened at intervals of about 18 months. No significant reduction of overall mortality and of lung cancer mortality was achieved. Semi-annual screening brought about a higher detection rate (9%/6.5%), an increase in the resection rate (28%/19%) and higher 5 and 10 year survival rates (52%; 27%/39%; 19%) of resected patients than screening in 18 month intervals. Among those patients who refused resection or were surgically untreatable, the difference in survival rates between the two investigation groups lasted only up to the 12 months barrier. This is regarded as the effect of the lead-time bias. Fluorographic screening is effective only in patients with peripheral cancers. Patients resected for central lung cancers did not show differences in the survival rates. In both investigation groups considered together surgical therapy was possible mainly in those patients who had been detected by screening (resection rate: 48%; 5 yr survival rate: 26.9%). The resection rate of all the others amounted to 9%, the 5 yr survival rate to 1.4%. Therefore we consider fluorography to time as the only chance for lung cancer control of high risk groups in spite of the absence of reduction of lung cancer mortality.

Adult↗