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Biomedical subjects

J Richter

Publications and source records attributed to J Richter.

At least 19 recordsLinked to original sources

Apollo: a sequence annotation editor.

The well-established inaccuracy of purely computational methods for annotating genome sequences necessitates an interactive tool to allow biological experts to refine these approximations by viewing and independently evaluating the data supporting each annotation. Apollo was developed to meet this need, enabling curators to inspect genome annotations closely and edit them. FlyBase biologists successfully used Apollo to annotate the Drosophila melanogaster genome and it is increasingly being used as a starting point for the development of customized annotation editing tools for other genome projects.

Animals

Effect of adenosine analogues and cAMP-raising agents on TNF-, GM-CSF-, and chemotactic peptide-induced degranulation in single adherent neutrophils.

Adenosine and adenosine analogues are potent inhibitors of the respiratory burst in neutrophils. Most investigators, however, have found little or no effect of these compounds on neutrophil degranulation from cytochalasin B-treated neutrophils in suspension. We have instead investigated the effect of adenosine and 2-chloroadenosine on degranulation in adherent neutrophils in the absence of cytochalasin B. Both adenosine and 2-chloroadenosine were effective inhibitors of lactoferrin secretion induced by the chemotactic peptide N-formyl-methionine-leucyl-phenylalanine (fMLP) [50% inhibitory concentration (IC50) of less than 10(-6) M]. Secretion induced by tumor necrosis factor (TNF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) was inhibited only at high concentrations (IC50 of approximately 10(-4) M). In the presence of cytochalasin B no inhibitory effect of 2-chloroadenosine was seen. The effect of cAMP-raising agents on secretion from adherent neutrophils was also investigated. Dibutyryl cAMP at 0.2 mM reduced secretion in response to fMLP by 50% but did not inhibit TNF- and GM-CSF-induced degranulation. At a concentration of 2.0 mM dibutyryl cAMP also inhibited exocytosis in response to the two cytokines. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) at 300 microM reduced fMLP-induced degranulation, whereas a concentration of 1 mM was required to inhibit TNF- and GM-CSF-mediated secretion. The adenylate cyclase activator forskolin (50 microM) alone did not inhibit secretion in response to TNF or fMLP. However, in combination with IBMX (300 microM), forskolin (50 microM) reduced both TNF- and fMLP-induced secretion to less than 10%. PMA-induced exocytosis was unaffected by all these agents. In conclusion, adenosine appears to be an effective inhibitor of neutrophil granule protein secretion induced by fMLP but only a weak inhibitor of exocytosis in response to TNF or GM-CSF. Secretion in response to fMLP was also found to be more susceptible to a rise in cAMP than degranulation induced by TNF and GM-CSF.

1-Methyl-3-isobutylxanthine

Morphological investigation of the porcine liver directly following preservation with Euro-Collins, University of Wisconsin and Bretschneider's HTK solution.

In order to study perfusion effects of different liver preservation methods on liver structure, porcine livers were perfused with either Bretschneider's HTK (Histidine Tryptophane Ketoglutarat) solution, Euro-Collins (EC) solution or University of Wisconsin solution (UW) according to the respective recommended protocols. Subsequently, together with a group of unprotected livers, all organs were examined by light and electron microscopy including computer assisted morphometry. The width of the space of Disse, the continuity of endothelial cells and the ultrastructure of the hepatocytes were not impaired after cold perfusion with any of the 3 solutions. However, we found considerable differences between the groups with respect to removal of blood cells from liver sinusoids. Livers flushed according to the HTK-protocol had the lowest residual blood cell content followed by the livers of the EC- and the UW-group. Centrilobular regions of the liver lobules were generally better washed free of blood than periportal zones. Computer assisted morphometry did not reveal any significant difference between the size of hepatocytes of EC-, UW- and HTK livers. Only the hepatocytes of normothermic control livers (biopsy samples) were 10% larger than hepatocytes of cold flushed groups. None of the protective perfusion protocols showed structural signs of perfusion injury.

Adenosine

Sonographic organometry in Brazilian and Sudanese patients with hepatosplenic schistosomiasis mansoni and its relation to the risk of bleeding from oesophageal varices.

Fifty-nine patients with hepatosplenic schistosomiasis mansoni were investigated by sonography in Northeast Brazil and Central Sudan. The sizes of the organs usually involved in this disease were quantitatively assessed according to a standardized protocol, and measurements were adjusted to the body height of the individual. The results were compared with those of healthy controls matched by sex, age, geographical origin and socio-economic status. Considerable differences were found between patients and controls as well as between residents from the two areas. The liver of both patients and controls from the Sudan was significantly smaller than that of patients and controls from Brazil. Only in Brazil, but not in the Sudan, was the left liver lobe larger in patients than in the controls. The diameter of the portal and the splenic vein, the spleen size and the thickness of the gallbladder wall were significantly increased in patients from both areas. The increase of the portal and splenic vein diameter was significantly correlated with the degree of hepatic periportal fibrosis and the frequency of bleeding from endoscopically proven oesophageal varices in the patients, irrespective of their geographic origin. In contrast, such correlations were not found for the degree of splenomegaly nor for the degree of gallbladder-wall thickening. It is concluded that standardized sonographic organometry permits the assessment of morbidity in hepatosplenic schistosomiasis mansoni under different endemic conditions. Especially the measurement of the portal vein diameter may allow estimation of the risk of gastrointestinal haemorrhage in these patients.

Adolescent

Electron spectroscopic study (ESI, EELS) of Nanoplast-embedded mammalian lung.

The potential of Nanoplast melamine resin embedding for the study of mammalian lung parenchyma was examined by means of electron spectroscopic imaging (ESI) and electron energy-loss spectroscopy (EELS). Samples were either fixed with glutaraldehyde-paraformaldehyde or glutaraldehyde-tannic acid, or were directly transferred to the embedding medium without prior fixation. Organic dehydrants, as well as fixatives containing heavy metals and stains, were omitted. A very high level of ultrastructural detail of chromatin, ribosomes, mitochondria and plasma membranes was achieved by ESI from the Nanoplast-embedded samples. The most prominent gain in ultrastructural detail was achieved when moving from an energy loss just below the L2,3 edge of phosphorus at 132 eV to an energy loss just beyond this edge. This reflects the prominent P L2,3 edge observed by EELS of Nanoplast-embedded samples in comparison with conventionally processed samples. Thus, taking into account possible sectioning artefacts, excellent heterochromatin images which rely on the phosphorus distribution can be obtained from Nanoplast-embedded samples by computer-assisted analysis of electron spectroscopic images. In this respect glutaraldehyde-paraformaldehyde fixation is preferable to glutaraldehyde-tannic acid fixation because the presence of silicon, revealed by EELS, in tannic-acid-fixed samples may introduce artefacts in phosphorus distribution images obtained by the three-window method because of the close proximity of the L2,3 edges of silicon and phosphorus.

Animals

The receptors for regulatory molecules of hematopoiesis.

Proliferation and differentiation of hematopoietic cells are controlled by pleiotropic regulatory molecules. While the sequences of these factors are not related, their membrane receptors are restricted to two gene families with homologous domains. The members of the hematopoietic (or cytokine) receptor family (for erythropoietin, interleukins-2, -3, -4, -6 andu-7, granulocyte-macrophage and granulocyte colony-stimulating factor) are composed of multiple subunits necessary for high-affinity binding and cell signalling. Signal transducing mechanisms are largely unknown. The occurrence of variant signal transducers in different tissues could explain the pleiotropy of these regulatory molecules. Members of the receptor tyrosine kinase family bind dimeric forms of macrophage colony-stimulating factor, stem cell factor and platelet-derived growth factor leading to kinase activation and phosphorylation of many substrates involved in production of second messengers. Soluble forms (binding proteins) exist for members of both families. These may be proteolytic cleavage products of transmembrane receptors or naturally secreted products. Such binding proteins can potentially function as inhibitors in feedback regulation and in protection and transport of cytokines and would provide a rational therapy when cytokines are produced in excess. Knowledge of signal transduction mechanisms and of the three-dimensional structure of ligands and receptors can lead to the design of drugs with cell-specific effects.

Animals

Hepatosplenic schistosomiasis: comparison of sonographic findings in Brazilian and Sudanese patients--correlation of sonographic findings with clinical symptoms.

Twenty-seven Brazilian and 32 Sudanese patients with hepatosplenic schistosomiasis from areas where the disease is endemic were examined with ultrasound (US). Hyperechoic periportal areas indicating periportal fibrosis (PPF) were present in all patients irrespective of their origin. Nonspecific findings were splenomegaly (all patients), gallbladder wall thickening (81% and 92%, respectively, in Brazilian and Sudanese patients), portal vein (74% and 87%, respectively) and splenic vein (59% and 70%, respectively) enlargement, and portosystemic vascular shunts (62% and 61%, respectively). The hepatic alterations were congruent and the frequency of their occurrence was similar in both patient groups. With a standardized grading system, it was shown that grade of PPF was significantly correlated with a history of bleeding from endoscopically proved esophageal varices and with distention of the portal vein as measured with US. It was concluded that sonographic grading may be used in patients with hepatosplenic Schistosoma mansoni infection who originate from completely different endemic areas.

Adolescent

Determinants of recall of parental rearing behavior. The influence of age or loss of parents by separation or death.

In a study of 562 psychiatric inpatients and 251 healthy controls, relationships between age of proband and related life events (divorce of parents, death of a parent) and the perceived parental rearing have been investigated. The inverse relationships obtained could be explained by the higher number of divorced parents among younger subjects with negatively experienced parental rearing practices on the one hand and an idealization of the parents who had died on the other hand. In psychiatric patients these relationships and differences were more pronounced pointing to the importance of parental rearing as a vulnerability factor for mental problems during adulthood. The necessity to control for age in studies of perceived parental rearing became obvious by the present results.

Adult

Provider/client views: health-care needs of the rural elderly.

Health-care providers perceived the following issues as influencing service use among rural elderly: financial restraints, eligibility requirements, values, geographic location, coordination of services, transportation, knowledge of normal aging, and family education. The elderly cited the following as influencing their acceptance of services: self-perceptions, fear of dependence, lifetime skills, finances, and maintaining dignity. More research is necessary to determine the "true" needs of older adults in rural areas so that service provision can effectively be modified to meet existing and future needs.

Aged

Ultrasonographical investigation of periportal fibrosis in children with Schistosoma mansoni infection: reversibility of morbidity twenty-three months after treatment with praziquantel.

In February 1987, 322 Sudanese school children were diagnosed for Schistosoma mansoni infection and treated randomly with praziquantel (either 20 mg/kg or 40 mg/kg body weight). A followup of these subjects was carried out in January 1989. This treatment resulted in a substantial reduction of egg output. Patients underwent complete abdominal ultrasonography and periportal fibrosis of the liver was graded into three degrees of severity. The proportion of patients with periportal fibrosis decreased from 36.6% in February 1987 to 21.7% in January 1989. At the time of followup, higher grades of periportal fibrosis (grades II and III) were encountered in only 4.3% and 0.3% of these patients, respectively, compared with 21.1% and 5.9%, respectively, before therapy. This was paralleled by a significant decrease in hepatomegaly from 10.9% to 7% of the patients. In contrast, the rate of splenomegaly showed a slight increase during the period of observation. The different dosage regimens of praziquantel did not result in a significantly different reversibility of periportal fibrosis or a decrease in egg excretion. The reversibility of specific liver lesions 23 months after antischistosomal therapy with praziquantel was substantial. The improvement was greater at 23 months than that obtained seven months after treatment.

Adolescent

Ultrasonography as a diagnostic aid for a district hospital in the tropics.

To improve diagnostic capabilities, an ultrasound unit was installed at a major hospital in Wad Medani, Sudan. During the implementation period (October 1986 to March 1987) of ultrasound service, 863 patients were examined cooperatively by Sudanese and German physicians. The service covered internal medicine (47.5%), obstetrics and gynecology (31.6%), surgery (12.5%), and pediatrics (8.4%). Pathologic findings were seen in 75% of the patients. In obstetrics, the rate of pathologic findings was 40%. Five hundred eighty-three pathologic findings were detected in organ systems that constituted the primary indication for ultrasonography (of a total of 1,009 indications). The clinical benefit of ultrasonography was evaluated in 289 randomly selected patients in a standardized questionnaire completed by the attending physicians. The final clinical diagnosis was established or substantially revised in 21.5% of the patients, based on the ultrasonographic report. The previously reported diagnosis was supported in 69.5% of the patients. Medical management was directly influenced in 26% of the patients. We conclude that the clinical benefit of ultrasonography at a district hospital in the tropics is substantial, providing cost-effective, immediate therapeutic benefits in 25% of the patients examined. The technique thereby contributes to better and more rational patient management in institutions with limited resources.

Adolescent

Calcitonin gene-related peptide (CGRP) activates human neutrophils--inhibition by chemotactic peptide antagonist BOC-MLP.

The effect of the neuropeptides substance P, neurokinin A and alpha-calcitonin gene-related peptide (CGRP) on human neutrophil granulocytes was investigated. Substance P induced secondary granule secretion at a concentration of 100 microM. CGRP induced a significant secretory response at 10 microM and thus appeared to be about 10 times more potent than substance P. Calcitonin and a fragment of CGRP, CGRP(8-37), had no effect on neutrophil degranulation. The chemotactic peptide antagonist BOC-MLP (100 microM) inhibited lactoferrin secretion mediated both by CGRP and chemotactic peptide FMLP almost completely, while secretion in response to tumour necrosis factor (TNF) was unaffected. Results from receptor binding studies showed that CGRP and N-formyl-methionyl-leucyl-phenylalanine (FMLP) do not compete for binding. This indicates that CGRP does not exert its effects by binding to the chemotactic peptide receptor. CGRP induced a rapid increase in the cytosolic-free calcium concentration and this increase was not, unlike that induced by FMLP, abolished by preincubation of the cells with pertussis toxin (1000 ng/ml). Therefore CGRP signal transduction in neutrophils appears to involve rapid changes in the cytosolic-free calcium concentration but not a pertussis toxin-sensitive G-protein. In summary, this is the first report to show that CGRP can directly activate neutrophil granulocytes, and this probably occurs via a cell surface receptor which is distinct from that of FMLP although both the CGRP and FMLP-mediated effects can be blocked by BOC-MLP.

Calcitonin Gene-Related Peptide

Ultrasound versus clinical examination as indication for Schistosoma mansoni associated morbidity in children.

In order to compare clinical versus ultrasound based diagnosis of Schistosoma mansoni induced periportal fibrosis (pF) 536 infected Sudanese schoolchildren underwent clinical and sonographical examination. A liver exceeding 3 cm in sternal line and a palpable spleen were considered pathological. Ultrasound criteria for age dependent organometry of a Central European cohort were used as reference. Based on clinical criteria 190 children (35.4%) had hepatomegaly, whereas according to ultrasound results the rate was only 11.4%. Splenomegaly was detected in 77 cases (14.4%) by clinical means, but in 196 by ultrasound (36.6%). The sensitivity of clinical parameters as indication of pF was around 50%. Results for ultrasound detected organomegaly were only slightly better. It was concluded that assessment of liver and spleen sizes was of limited value as an indication for pF and that a considerable discrepancy existed between clinical and ultrasound based assessment of hepato- and splenomegaly.

Adolescent

[Tuberous sclerosis: broadening of the diagnosis using MR tomography and computed tomography].

Ten children and a 22-y old women with tuberous sclerosis were studied. All children were epileptic but only 8 had skin lesions (white spots, sebaceous adenoma), 4 had rhabdomyoma of the heart and 4 children had astrocytoma of the retina; only in 4 children was the entire triad of tuberous sclerosis seen. The young woman with a hemorrhage of an angiolipoma of the kidney had no other symptoms of tuberous sclerosis. All patients had pathologic CT and MRT findings; 4 different types of lesion were seen in MRT. In order to elucidate human genetic aspects and to demonstrate the underlying disease all children with epileptic disorders and also all patients without the full triad of symptoms should be examined by MRT.

Adult

[Mucosal candidiasis].

The authors demonstrate the case of a female patient with a prolonged mucosal form of candidosis caused by different biotypes of Candida albicans. Despite the fact the long-term and repeated treatment with Nizoral and transfer factor was applied, relapses of the disease developed. Marked improvement of clinical manifestations occurred only after a change of the dietary habits and long-term administration of immunomodulating agents. The authors discuss therapeutic and diagnostic aspects of the disease.

Candidiasis