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Biomedical subjects

J Richter

Publications and source records attributed to J Richter.

At least 235 records · Page 13Linked to original sources

Close correlations between mitochondrial swelling and ATP-content in the ischemic canine myocardium. A combined morphometric and biochemical study.

This study investigates how far mitochondrial swelling in the ischemic heart is influenced by factors pertaining to anaerobic energy turnover. Canine hearts were arrested by aortic cross clamping or cardioplegically with St. Thomas or HTK solution and incubated at 25 degrees C in the solution used for cardiac arrest. Samples of the left ventricle were taken at the end of cardiac arrest and during ischemia for structural evaluation and biochemical analysis. The extracellular pH in the interventricular septum was measured. Mitochondrial swelling was determined with the surface to volume ratio, a parameter independent of the reference space. Values obtained for different swelling were related to defined metabolite concentrations and pHe values to establish possible correlations between structural and biochemical parameters in the ischemic heart. At the onset of ischemia and during the breakdown of creatine phosphate (CP) to 3 mumol/g wet weight mitochondrial volume depends on the method of cardiac arrest and does not increase significantly in any of the three groups. The degree of mitochondrial swelling after depletion of CP correlates with the decline in ATP independent of the form of cardiac arrest. Characteristic values of the surface to volume ratio ascertained at different times of ischemia for all groups correspond to determined ATP concentrations. Acid pHe values seem to intensify mitochondrial swelling. With increased lactate concentrations mitochondria swell, but first initially the degree of swelling differs significantly in the forms of cardiac arrest investigated. Thus, the surface to volume ratio is a powerful and valid ultrastructural parameter, which makes correlations between mitochondrial structure and metabolism possible and furthermore indicates a strong correlation between mitochondrial swelling and ATP-concentration in the ischemic heart.

Adenosine Triphosphate↗

Immunochemotherapy of visceral leishmaniasis: a pilot trial of sequential treatment with recombinant interferon-gamma and pentavalent antimony.

The clinical, parasitological, hematological, and serological evolution of visceral leishmaniasis in Brazilian patients was assessed during treatment with human recombinant interferon-gamma (rIFN-gamma; 0.1 mg/m2 i.m. days 1-14) followed by pentavalent antimony (Sbv; 10 mg/kg days 22-28). At day 30, 6 patients had improved, 2 had slightly improved, and 1 patient had deteriorated. IFN-gamma was well tolerated in the dose tested and may be very effective as an adjunct to conventional therapy with antimony.

Adolescent↗

Correlation between serum level of soluble L-selectin and leukocyte count in chronic myeloid and lymphocytic leukemia and during bone marrow transplantation.

L-selectin is a glycoprotein which is one of three members in a family of cell adhesion molecules called selectins. L-selectin is present in distinct forms on both neutrophil granulocytes and lymphocytes, and it appears to play an important role in the early stages of leukocyte-endothelial cell interaction. Activation of leukocytes leads to shedding of the extracellular part of L-selectin which thus forms a soluble adhesion molecule, sL-selectin, which retains functional capacity and can be detected in serum. In the present study we have developed a specific, sensitive sandwich ELISA to measure the serum level of sL-selectin in patients with hematological and infectious disorders. Three patients with acute myeloid leukemia in remission and 1 patient with chronic myeloid leukemia in chronic phase were followed during bone marrow transplantation and the level of sL-selectin was found to correlate closely to the leukocyte counts with no detectable sL-selectin during periods of severe leukopenia. In 11 patients with chronic phase chronic myeloid leukemia and 13 patients with chronic lymphocytic leukemia the sL-selectin level was also found to correlate closely to the leukocyte count (R = 0.98; p = 0.001 and R = 0.83; p = 0.004 respectively). One CML patient with a leukocytosis of 385 x 10(9)/l was found to have an sL-selectin concentration 625 times above normal. Ten patients with acute pneumonia were evaluated at diagnosis and at the time of follow-up 4-8 weeks later. In all patients the initial sL-selectin level was higher than at follow-up. However, no close correlation between sL-selectin and leukocyte count or CRP (C-reactive protein) at the time of diagnosis was found. In summary, we have found that the sL-selectin level in human serum closely correlates to the leukocyte count in both CML and CLL and during bone marrow transplantation.

Acute Disease↗

[Biliary fistula after concealed choledochal rupture in a polytraumatized patient].

This paper describes the case of a polytraumatised patient. Following primary care, a persistent fistulous wound developed. After initially good healing, the patient progressively deteriorated. Extensive diagnostic workup revealed a maximally elevated bilirubin concentration in the wound secretion. Five years previously, the patient had undergone a cholecystectomy. A leak in the common bile duct caused by the trauma was detected and was treated with a biliodigestive anastomosis with a Roux-Y loop, and bypass of the distal common bile duct.

Aged↗

Influences of the environmental pollution on the immune system: some recent views.

The authors discuss the contemporary progress in preventive immunology with special attention to unfavourable effects of environmental pollution. They followed-up these problems systematically for more than twenty years and in this paper they present some of their results. They stress the importance of the protective effect of balanced nutrition with an adequate supply of vitamins and trace elements. The unfavourable effect of pollution is documented by different health aspects of the population living in the heavily polluted region of Northern Bohemia.

Adolescent↗

Carboplatin-liposomes as activators of hematopoiesis.

Recombinant colony stimulating factors are studied in clinical trials with the purpose being the relief of the side effects of high dose chemotherapy and to make an optimized treatment regimen possible. The broad use of such factors is hindered by their relatively high costs, their short elimination half-lives, the occurrence of mild side effects, and the limitation of their action to the stimulation of mainly neutrophils. Therefore, exogenous preparations inducing an endogenous activation of hematopoiesis are being sought. In experiments in mice we have shown that carboplatin-liposomes injected intraperitoneally in a single dose of 100 mg/kg led to a strong two-peak increase in white blood cell counts. A maximum 10-fold elevation compared to controls of free carboplatin or empty liposomes was observed on day 2 and was probably due to the release and mobilization of cells from storage compartments. The second peak of about a 6-fold increase occurred on day 7-8 and can be seen as an indicator of bone marrow stimulation. Differentiation of blood cells revealed that neutrophils, lymphocytes and platelets multiplied. We presume that this effect of carboplatin-liposomes is due to a relatively fast uptake of these vesicles by macrophages as their natural target. Within these cells carboplatin is metabolized, leading to an almost total loss of antineoplastic activity against the murine P388 leukemia. Concomitantly, cytokines are apparently induced in and released from macrophages producing secondarily hematopoietic growth factors either directly or in combination with other cytokines. An involvement of macrophages is indicated by the fact that an intraperitoneal pretreatment of mice with zymosan caused a partial but significant suppression of hematopoietic stimulation. In an in vitro colony forming assay of serum of mice treated 1, 3, or 7 days with carboplatin-liposomes, the number of colonies increased 20-fold compared to serum from saline treated animals. Additionally, a combined intraperitoneal treatment of mice with 100 mg/kg of cyclophosphamide followed by carboplatin-liposomes one hour later demonstrated that prevention of cytostatic-induced leukopenia is possible by this method. Although the mechanism of stimulation of hematopoiesis by carboplatin-liposomes is still partially unknown our results suggest that there should be further development of such a preparation for possible use in the treatment of cancer or other inherited or acquired hematopoietic disorders.

Animals↗

Respiratory distress syndrome. A suggestive pattern of shunt effect detected by means of macroparticles.

An esophagobronchial fistula developed in a patient who had well-differentiated squamous carcinoma of the lung that was treated with chemotherapy. Because the esophagobronchial fistula could not be surgically repaired, it was isolated with a mechanical stitch above and below it. Forty-eight hours after initiation of enteral nutrition, a perfusion lung scan was performed because of clinical suspicion of pulmonary embolism. Because the scan showed reduced pulmonary radioactivity and accumulation of activity in the kidneys and spine, an arteriovenous shunt was suspected. However, subsequent digital subtraction angiography ruled out this possibility and a recurrence of the esophagobronchial fistula was confirmed with an esophagogram. The unusual extrapulmonary activity could be related to a reversible capillary shunt in the pulmonary vasculature, secondary to acute respiratory distress syndrome.

Antineoplastic Combined Chemotherapy Protocols↗

Interrelations between electrical and biochemical processes in ischemic porcine livers at low temperature.

Recently it has been shown that during liver ischemia at 25 degrees C the presence of glycogen, by supporting glycolytic supply, not only retards ATP decay but also leads to a corresponding delay of the rise of the electrical impedance of the ischemic organ. A sudden rise of impedance during ischemia is supposed to indicate the closure of gap junctions. Although similar effects on energy state do exist at low temperature, the impact of glycogen on the electrical impedance under storage conditions has still to be evaluated. Therefore, in a model with protected porcine livers, we examined the intraischemic effects of a preischemic glucose and potassium feeding on impedance changes, lactate production and ATP-content at a storing temperature of 5 degrees C. Impedance was measured both in the low frequency alpha- and the higher frequency beta-dispersion range. In addition, the same parameters were determined in a group of unprotected livers. In this group all animals had received glucose and potassium orally prior to ischemia. Whereas in case of preischemic glucose feeding the rise of impedance in the range of the beta-dispersion (e.g. 5kHz) roughly coincided with the exhaustion of ATP, the corresponding impedance changes in the protected group without a glucose premedication only occurred when glycolysis had already stopped and ATP had reached basal values for some hours. In contrast, in the alpha-dispersion range the impedance changes in the latter group just began at the time when ATP became exhausted and lactate production ceased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

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↗