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Biomedical subjects

K Richter

Publications and source records attributed to K Richter.

At least 127 records · Page 7Linked to original sources

Assessment of accuracy and applicability of a new electronic peak flow meter and asthma monitor.

The aim of this study was to assess the accuracy and applicability of a portable electronic peak flow meter combined with an asthma monitor (AM1, Jaeger, Germany) which measures peak expiratory flow (PEF), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). The technical accuracy in PEF, FEV1 and FVC measurement was tested according to American Thoracic Society (ATS) criteria for monitoring devices using a flow generator. In addition, the effect of connecting a heated screen pneumotachograph (PT) to the AM1 was determined and the accuracy in FEV1 determinations was evaluated by simultaneous measurements in 49 normal volunteers. The devices tested fulfilled all ATS criteria for monitoring devices with respect to the accuracy of PEF, FEV1, and FVC measurements. The conditions of intra- and interdevice variability were satisfied in all cases. Compared with the PT, the AM1 showed about 4% lower values in FEV1, as measured in the 49 subjects. In conclusion, the electronic peak flow meter and asthma monitor AM1 yielded valid measurements of peak expiratory flow and forced expiratory volume in one second, which matched the accuracy criteria of the American Thoracic Society standards for monitoring devices.

Adult↗

Plasma levels and gene expression of granulocyte colony-stimulating factor, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 in neonatal early onset sepsis.

Bacterial sepsis is still a leading cause of neonatal morbidity and mortality. Early onset sepsis in particular, presents with a different clinical course and involves other pathogens than sepsis later in life. In this study, plasma concentrations and mRNA expression of granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 (sICAM-1) of neonates with early onset sepsis were evaluated in cord blood and during the first days of life. Irrespective of prematurity, plasma levels of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8, but not sICAM-1, were excessively elevated in septic neonates when compared with both healthy infants and infants with clinically suspected but not confirmed sepsis. Compared with the corresponding maternal levels, neonatal cytokine cord plasma levels were likewise highly elevated, indicating the endogenous cytokine production by the neonate. With the exception of TNF-alpha, mRNA expression in blood cells from septic infants was, however, not more frequently detectable than in those from nonseptic patients. Cytokine levels decreased significantly within the first days of life, whereas levels of sICAM-1 and C-reactive protein increased during the same time period. In summary, in contrast to C-reactive protein and sICAM-1, cord blood plasma levels, but not the presence of mRNA, of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8 can predict neonatal early onset sepsis with a high sensitivity and specificity. Cell types other than blood cells are likely to contribute considerably to the high cytokine production in septic newborns.

Bacteremia↗

[Combination of mammography with automated ultrasound (Sono-X) in routine diagnosis?].

A new technique for breast imaging is presented. This technique combines radiographic mammography directly with automated ultrasound. The combined examination, which is performed without decompression of the breast, yields the conventional mammography films as well as a complete set of B-mode scans and ultrasound projections. These can be geometrically matched with each other in a definitive manner. A prototype of the device was first used in a pilot study of 50 patients followed by a study of an additional 450 patients with a total of 492 breast lesions, of which 269 were confirmed by histology or cytology. The results show that X-ray and ultrasound are complementary in the detection of cancer. The use of an experimental mode of image interpretation for combined mammography and automated ultrasound reduced the number of mammographically suspicious findings that ultimately turned out to be benign. These results were also confirmed in two blind studies including a total of 160 histologically or cytologically confirmed lesions and 40 cases without lesions. With further technical advancement of the technique aimed at rapid and easy application and confirmation of the results obtained so far, the combination of mammography and automated ultrasound might be introduced into a routine clinical setting.

Breast↗

Immunological and biological properties of Bet v 4, a novel birch pollen allergen with two EF-hand calcium-binding domains.

We have isolated a cDNA clone coding for a birch pollen allergen, Bet v 4. The deduced amino acid sequence of Bet v 4 contained two typical EF-hand calcium-binding domains. Sequence similarities of Bet v 4 to calmodulin are primarily confined to the calcium-binding domains. However, significant sequence similarities extending outside the Ca2+-binding sites were found with a recently described group of pollen-specific allergens of Brassica and Bermuda grass. Both EF-hand domains of Bet v 4 are able to bind Ca2+, as demonstrated by 45Ca2+ blot overlay of wild type and calcium-binding deficient mutants of Bet v 4. Among pollen-allergic patients, protein-bound Ca2+ was not an absolute requirement for IgE recognition of Bet v 4. However, disruption of the carboxyl-terminal Ca2+-binding domain indicated that most IgE antibodies from allergic patients are directed against this site. IgE inhibition experiments suggested that Bet v 4 represents a highly cross-reactive pollen allergen. Pre-absorption of allergic sera with Bet v 4 drastically reduced IgE binding to proteins of similar molecular weight in pollen extracts from distantly related plant species (e.g. timothy grass, mugwort, lily) but not in extracts from plant-derived foodstuff. To test for a possible biological role in pollen germination and tube growth, we introduced recombinant Bet v 4 protein into growing lily pollen tubes by iontophoresis. As a result, cytoplasmic streaming stopped in the vicinity of the electrode tip, and a slight depolarization of the membrane voltage was measured. These effects were not observed with Ca2+-binding deficient mutants of Bet v 4. Thus, Bet v 4 and homologous proteins represent a new class of pollen-specific Ca2+-binding allergens that may have a physiological role as inhibitors of cytoplasmic streaming in outgrowing pollen tubes.

Allergens↗

A member of the Met/HGF-receptor family is expressed in a BMP-4-like pattern in the ectoderm of Xenopus gastrulae.

The importance and involvement of growth factors and their corresponding receptors in embryonic induction has been more and more recognized during the past decade, in particular by loss-of-function experiments using dominant negative receptors. Here, we report the isolation of XHR, a Xenopus receptor-type tyrosine kinase, with homology to members of the Met/hepatocyte growth factor (HGF)-receptor family. Sequence comparison of XHR with other members of the Met/HGF-receptor family as well as in situ expression analyses suggest that XHR represents a novel member of this family of receptor-type tyrosine kinases. As could be shown by whole-mount in situ analysis, XHR transcripts are first expressed in the entire ectoderm at the onset of gastrulation. As gastrulation proceeds, XHR-transcription is turned off in cells induced by dorsal mesoderm to form neural tissue and thus, becomes predominantly confined to prospective epidermis. The strikingly similar expression patterns of XHR and Bone Morphogenetic Protein-4 (BMP-4), an inducer of epidermis and inhibitor of neural development, suggest an involvement of XHR signalling in the early cell-fate decision of ectodermal cells to form either neural derivatives or epidermis.

Animals↗

Suspected ehrlichial infection in five cats from a household.

Ehrlichiosis is a poorly recognized condition of cats that may be associated with anemia, leukopenia, thrombocytopenia, or dysproteinemia. Affected cats may have indirect fluorescent antibody titers to Ehrlichia canis and E risticii. We reviewed the clinical evaluation and response to treatment of 5 cats in a household where ehrlichial disease was suspected as the cause of recurrent leukopenias and thrombocytopenias. All of the cats had E risticii indirect fluorescent antibody titers and western blot confirmation of antibodies to 4 of the 9 major antigens of E risticii. Response to doxycycline was monitored serologically and hematologically in each cat, and indicated that administration of doxycycline at a dosage of 10 mg/kg of body weight, PO, every 12 hours, for a minimum of 21 days is necessary for treatment of this condition.

Animals↗

Effect of codeine on gastrointestinal motility in relation to CYP2D6 phenotype.

BACKGROUND: Codeine is widely used as an analgesic and antitussive drug. The analgesic effect of codeine is mediated by its metabolite morphine, which is formed by the polymorphically expressed enzyme CYP2D6; therefore poor metabolizers have no analgesia after administration of codeine. Like other opiates, codeine causes a delay of gastric emptying and spastic constipation. It is not yet known whether the effect on gastrointestinal motility is mediated by codeine or its metabolite morphine. METHODS: To test the hypothesis that the metabolite morphine is responsible for the effects of codeine on gastrointestinal motility, a randomized, double-blind, two-way crossover study was performed. The orocecal transit time was studied in five extensive and five poor metabolizers of sparteine with the sulfasalazine-sulfapyridine method, assuming that no effects are observed in poor metabolizers because negligible amounts of morphine are formed. RESULTS: No differences of orocecal transit times were observed between extensive metabolizers and poor metabolizers after oral placebo administration. However, after oral codeine administration orocecal transit time was significantly prolonged in extensive metabolizer but not poor metabolizer subjects. All pharmacokinetic parameters of codeine showed no differences between extensive metabolizers and poor metabolizers. The pharmacokinetic parameters (mean +/- SD) of the metabolite morphine were significantly different between extensive metabolizer and poor metabolizer subjects (peak serum concentration, 13.9 +/- 10.5 versus 0.68 +/- 0.15 pmol/ml; area under the serum concentration-time curve, 27.8 +/- 16.0 versus 1.9 +/- 0.7 hr.pmol/ml; total amount of morphine excreted in urine, 0.160 +/- 0.036 versus 0.015 +/- 0.007 mumol). CONCLUSIONS: Because the orocecal transit time prolongation after codeine administration was observed only in extensive metabolizers, the effect of codeine on gastrointestinal motility, like the analgesia, is mediated by its metabolite morphine.

Analgesics, Opioid↗

The molting gland of the cockroach Periplaneta americana: secretory activity and its regulation.

1. The prothoracic gland is the main source of ecdysteroids in larvae of the cockroach Periplaneta americana. 2. Besides ecdysone the molting gland of Periplaneta secretes 3-dehydroecdysone and proteins. 3. The molting gland of Periplaneta is regulated in different successive steps of cooperation of nervous and neuroendocrine activity. 4. Neurogenic effects on the molting gland via the prothoracic gland nerves are concentrated on the period of prepeak production of ecdysteroids. 5. Prior to the 17th day, the glands secretory activity is inhibited by GABA-ergic neuronal pathways from the subesophageal ganglion. 6. Neurogenic disinhibition by a peptidergic brain factor elicits the competence of the gland for prepeak activity, completed by the glandotropic effect of PTTH. 7. The 17th day of the larval stage is characterized as the head critical period, i.e., after this period the ecdysteroid secretion of the gland is independent of the prothoracicotropic hormone (PTTH) from the brain. 8. The main peak of ecdysteroid production is regulated by prothoracicotropic neuropeptids from the brain.

Animals↗

B-50/growth-associated protein-43, a marker of neural development in Xenopus laevis.

To study the regulation and function of the growth-associated protein B-50/growth-associated protein-43 (mol. wt 43,000) in Xenopus laevis, B-50/growth-associated protein-43 complementary DNAs were isolated and characterized. The deduced amino acid sequence revealed potential functional domains of Xenopus B-50/growth-associated protein-43 that may be involved in G-protein interaction, membrane-binding, calmodulin-binding and protein kinase C phosphorylation. The expression of B-50/growth-associated protein-43 at the RNA and protein level during development was investigated using the Xenopus complementary DNA and the monoclonal B-50/growth-associated protein-43 antibody NM2. The antibody NM2 recognized the gene product on western blot and in whole-mount immunocytochemistry of Xenopus embryos. Moreover, visualization of the developmentally regulated appearance of B-50/growth-associated protein-43 immunoreactivity showed that this mode of detection may be used to monitor axonogenesis under various experimental conditions. In the adult Xenopus, XB-50/growth-associated protein-43 messenger RNA was shown to be expressed at high levels in brain, spinal cord and eye using northern blotting. The earliest expression detected on northern blot was at developmental stage 13 with poly(A) RNA. By whole-mount immunofluorescence, applying the confocal laser scanning microscope, the protein was first detected in embryos from stage 20, where it was expressed in the developing trigeminal ganglion. Also later in development the expression of the B-50/growth-associated protein-43 gene was restricted to the nervous system in Xenopus, as was previously found for the mouse. In conclusion, we find that XB-50/growth-associated protein-43 is a good marker to study the development of the nervous system in Xenopus laevis.

Amino Acid Sequence↗

Use of a mass-thickness marker to estimate systematic errors and statistical noise in the detection of phosphorus by electron spectroscopic imaging.

The element signal obtained from electron-energy-filtered micrographs depends on the systematic error in calculating the background and on the noise in the background-corrected image. Both systematic error and statistical fluctuation of the background can be assessed experimentally with a specimen that combines the element-containing feature with a mass-thickness marker. The approach is described for the mapping of phosphorus in turnip yellow mosaic viruses prepared on a supporting carbon film of variable thickness. The thickness modulations are produced by the additional deposition of heat-evaporated carbon through a second grid used as a mask. The three-window power-law method and the two-window difference method are compared. With the three-window power-law method, the mass-thickness modulations of the marker are still visible in the map, indicating a systematic error for the calculated background. In addition, the intensity profile over the area of the thick carbon film is broader than in the map corrected by the two-window method, indicating a higher level of noise. With the two-window difference method, mass-thickness contrast was practically eliminated due to an improved protocol that uses the mass-thickness marker to calculate the scaling factor: instead of scaling the grey-level of a single background feature, the pre-edge image is scaled to the contrast of the marker area in the image acquired at the element-specific energy loss.

Electron Probe Microanalysis↗

Detection of low phosphorus contents in neurofilaments of squid axons by Image-EELS contrast spectroscopy.

We show that Image-EELS is suitable for detecting relatively low phosphorus concentrations in very small axoplasmic structures of squid axons. Imaging plates and a CCD camera were used as electron sensors. From image series spanning a certain energy-loss range EELS (electron energy-loss spectra) were derived by averaging read-outs from many axoplasmic particles (APs). The ratio of these spectra to spectra of the background was plotted, showing the contrast modulation as a function of the energy loss. This new approach is called EELC (electron energy-loss-dependent contrast spectroscopy). A distinct phosphorus signal was found in APs of presynaptic terminals of the squid giant synapse, in the peripheral giant axon and, as controls, in ribosomes. Biochemical experiments supported this result. In neurofilament-enriched pellets a phosphorus signal could be directly detected by serial EELS and in electron spectroscopic micrographs. After dephosphorylation of either the pellets or the extruded axoplasm with alkaline phosphatase, phosphorus signals in electron spectroscopic micrographs were absent or much reduced in size and intensity. With Image-EELS inherent limitations of traditional element detection modes in energy filtering transmission electron microscopy can be overcome. Compared with serial EELS, the selective analysis of small areas with irregular shape is possible with greatly improved signal-to-noise ratio. The identification of the element-peak in Image-EEL spectra directly proves the presence of the element within the region of interest. For small peaks, the visualization is facilitated by the contrast presentation (EELC). However, the background subtraction modes used for elemental mapping in electron spectroscopic imaging are subject to uncertainties when elemental ionization edges like the P1,2,3 edge are examined. Imaging plates are very sensitive electron sensors with a wide dynamic range. Unlike photographic emulsions, they allow acquisition of image series covering a large energy-loss range without normalization of exposure times, and direct extraction of EEL spectra. Thus, the combination of Image-EELS and imaging plates is proposed as an efficient new tool for analytical electron microscopy.

Animals↗

Effects of the novel NMDA antagonists CP-98,113, CP-101,581 and CP-101,606 on cognitive function and regional cerebral edema following experimental brain injury in the rat.

The present study evaluated the effects of two novel N-methyl-D-aspartate (NMDA) receptor blockers and ifenprodil derivatives, CP-101,606 and CP-101,581, and their racemic mixture CP-98,113, on spatial memory and regional cerebral edema following experimental fluid-percussion (FP) brain injury in the rat (n = 66). Fifteen minutes after brain injury (2.5 atm), animals received either (1) CP-98,113 (5 mg/kg, i.p., n = 11), (2) CP-101,581 (5 mg/kg, i.p., n = 13), (3) CP-101,606 (6.5 mg/kg, i.p., n = 12), or (4) DMSO vehicle (equal volume, n = 12); followed by a continuous 24-h subcutaneous infusion of drug at a rate of 1.5 mg/kg/h by means of miniature osmotic (Alzet) pumps implanted subcutaneously. Control (uninjured) animals were subjected to identical anesthesia and surgery without injury and received DMSO vehicle (n = 8); CP-98,113 (5 mg/kg, i.p., n = 3); CP-101,581 (5 mg/kg, i.p., n = 3); or CP-101,606 (6.5 mg/kg, i.p., n = 3). FP brain injury produced a significant cognitive impairment assessed at 2 days postinjury using a well-characterized testing paradigm of visuospatial memory in the Morris Water Maze (MWM) (p < 0.001). Administration of either CP-98,113, CP-101,581, or CP-101,606 had no effect on sham (uninjured) animals, but significant attenuated spatial memory impairment assessed at 2 days postinjury (p = 0.004, p = 0.02, or p = 0.02, respectively). Administration of CP-89,113 but not CP-101,581 or CP-101,606 significantly reduced the extent of regional cerebral edema in the cortex adjacent to the site of injury (p < 0.05) and in the ipsilateral hippocampus (p < 0.05) and thalamus (p < 0.05). These results suggest that excitatory neurotransmission may play a pivotal role in the pathogenesis of memory dysfunction following traumatic brain injury (TBI) and that blockade of the NMDA receptor may significantly attenuate cognitive deficits associated with TBI.

Animals↗

Description and first clinical use of a new system for combined mammography and automated clinical amplitude/velocity reconstructive imaging breast sonography.

RATIONALE AND OBJECTIVES: The authors tested a new automated system for clinical amplitude/velocity reconstructive imaging (CARI) breast sonography and compared the results with those of a manual laboratory model of this imaging modality, conventional sonography, and mammography. METHODS: Fifty-one patients with breast lesions were examined by mammography, conventional breast sonography, a laboratory version of a mammography-like breast compression device for breast sonography, and an automated system that allows sonography while in compression and reconstructs an image of the whole breast. The automated device allows reconstruction of one image per breast from an automatically acquired sonographic data set and simultaneous performance of mammography. The results of mammography and all modes of sonography were compared with histopathology in 36 surgically treated lesions of which 20 were benign and 16 malignant. In addition, 17 lesions confirmed to be benign by different imaging modalities were examined with the three different sonographic devices. RESULTS: All 16 histopathologically proven malignant lesions were identified correctly by compression sonography (laboratory and automated device) compared with 14 by conventional sonography. Of the 20 benign lesions, 16 were interpreted correctly by conventional sonography, 19 with the laboratory version, and 18 with the automated device, whereas mammography identified 12 benign lesions correctly and missed 1 malignant lesion. Only 16 of 17 lesions diagnosed to be benign by outpatient imaging could be examined with all three modes of study sonography and were found to be benign with all three modes in all cases. CONCLUSIONS: Compared with the laboratory version, the automated device facilitates acquisition and evaluation of compression breast sonography and is similar in lesion detection and differentiation. It should be tested in a larger number of patients.

Adult↗

Identification of aneuploidy in recurrent clear cell hidradenoma by DNA image cytometry (ICM-DNA).

Since malignant clear cell hidradenoma (CCH) is often characterized by only slight and sometimes by absent nuclear anaplasia, even in metastases, definitive differentiation from its benign counterpart by light microscopy may be very difficult. Herein, we report the case of a 72-year-old woman suffering from a CCH on the back, which showed local recurrence following incomplete excision. By light microscopy no unequivocal signs of malignancy were found either in the primary or the recurrent tumor. However, unusual deep extension to the subcutis with some architectural disorder was seen in the latter. Identification of prospective malignancy in such cases of borderline histopathological features is one of the main indications for diagnostic DNA image cytometry (ICM-DNA). Application of this method to enzymatic cell separation specimens of the recurrence detected marked DNA-aneuploidy with a stemline ploidy of 2.60 c and single events up to 6.7 c, whereas a nearly exact diploid DNA-stemline was found in the primary. We suppose from our results that a prospective malignant CCH with aneuploid DNA-stemline has developed out of its DNA-diploid counterpart. The need for total surgical removal of apparently benign clear cell hidradenomas is further stressed by this observation. Criteria for the diagnosis of malignancy in CCH are reviewed.

Adenoma, Sweat Gland↗

Detection of malignant and benign breast lesions with an automated US system: results in 120 cases.

PURPOSE: To evaluate clinically an automated ultrasound (US) system for detecting benign and malignant breast lesions. MATERIALS AND METHODS: A prototype automated US system was used to examine 119 patients: 38 patients with 39 proved malignant breast lesions (7-50 mm), 41 patients with 41 proved benign breast lesions (8-40 mm), and 40 patients without breast lesions. The device yields a three-dimensional set of B-mode scans and reconstructed US images comparable to mammograms. All patients had undergone mammography. Four radiologists who had not performed the examinations independently assessed the mammograms and US images to detect benign and malignant breast lesions. RESULTS: Each of the four readers did not recognize one to three detectable malignant lesions on mammograms, one to two detectable malignant lesions on US images, two to four detectable benign lesions on mammograms, and five to seven detectable benign lesions on US images. All readers identified the 39 cancers with at least one of the modalities. The 40 cases without lesions were diagnosed correctly more frequently on the US images by three readers and on the mammograms by one reader. CONCLUSION: Depiction of breast lesions at automated US is reproducible. Automated US is complementary to mammography.

Breast Diseases↗

Effect of intratubular application of angiotensin 1-7 on nephron function.

Cleavage of the C-terminal tripeptide of angiotensin I (Ang I) by neutral endopeptidase 24.11 releases angiotensin 1-7 (Ang 1-7). Because Ang I and neutral endopeptidase 24.11 are present in proximal tubular fluid and brush border, respectively, Ang 1-7 could be released into proximal tubular fluid to affect nephron function. Therefore, we studied the effect of intratubular Ang 1-7 (10(-12) to 10(-8) M) on nephron function employing in vivo renal micropuncture in inactin-anesthetized Munich-Wistar-Frömter rats. We observed that: (i) Intratubular application of Ang 1-7 for 3, 15, or 30 min did not affect reabsorption in the microperfused proximal convoluted tubule determined as net fluid reabsorption. (ii) During perfusion of Henle's loop for 15 min with artificial tubular fluid (time control), we observed a decline in fluid, potassium and sodium reabsorption by 20, 18 and 5%, respectively. A similar decline in reabsorption was seen with intratubular application of Ang 1-7 in a concentration of 10(-12) or 10(-10) M. In contrast, intratubular application of Ang 1-7 in a concentration of 10(-8) M increased fluid, potassium and sodium reabsorption in that nephron segment by 11, 9 and 3%, respectively. The latter response was completely abolished by AT1 angiotensin II receptor antagonist losartan (10[-6] M). (iii) Intratubular application of Ang 1-7 did not affect net sodium, potassium, or fluid reabsorption in the distal tubule. (iv) TGF response assessed by measuring proximal tubular stop-flow pressure or single nephron filtration rate during orthograde open-loop perfusion of Henle's loop was not significantly altered by intratubular application of Ang 1-7. These findings show that intratubular application of Ang 1-7 in concentrations which possibly cover the physiological range does not significantly alter (i) tubular reabsorption in proximal convoluted or distal tubule, or (ii) TGF response. Intratubular Ang 1-7 at a concentration of 10(-8) M appears to increase reabsorption in Henle's loop by an AT1 angiotensin II receptor-mediated mechanism, the physiological relevance of which remains to be established.

Absorption↗