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K Hahn

Publications and source records attributed to K Hahn.

At least 163 records · Page 9Linked to original sources

An oxonol dye is the most potent known inhibitor of band 3-mediated anion exchange.

When cells are acutely exposed to the oxonol dye, bis(1,3-dibutylbarbituric acid)pentamethine oxonol (diBA), at 0 degrees C, the concentration that gives half inhibition of Cl- exchange (IC50) is 0.146 +/- 0.013 microM (n = 12) initially, but the inhibition increases with time. These characteristics indicate that a rapid initial binding is followed by a slow conformational change that makes the binding tighter. If diBA is allowed to equilibrate with band 3, the IC50 is only 1.05 +/- 0.13 nM (n = 5), making diBA a more potent inhibitor than 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), for which the IC50 under similar conditions is 31 +/- 6 nM [T. Janas, P. J. Bjerrum, J. Brahm, and J. O. Wieth. Am. J. Physiol. 257 (Cell Physiol. 26): C601-C606, 1989]. Inhibition by diBA is very slowly reversible at 0 degrees C (t1/2 > 50 h), but the effect is more readily reversible at higher temperatures. DiBA competes with 4,4'-dinitrostilbene-2,2'-disulfonate (DNDS) for inhibition, suggesting an external site of action. In contrast to DIDS and DNDS, however, increasing Cl- concentrations do not decrease the inhibitory effect of diBA, indicating that the inhibition is not competitive. Thus diBA may be useful for investigating conformational changes during anion exchange and for stopping transport without preventing substrate binding. However, when diBA and other oxonols are used to sense membrane potential, they may have undesirable side effects on anion transport processes.

Anion Exchange Protein 1, Erythrocyte↗

Indium-111-pentetreotide scintigraphy in Graves' ophthalmopathy.

UNLABELLED: The radiolabeled somatostatin analog 111In-pentetreotide can sensitively demonstrate somatostatin receptor-positive localizations in diseases where activated lymphocytes play a role. Lymphocyte infiltration of retrobulbar tissue in Graves' ophthalmopathy is the rationale of receptor imaging with radionuclide-coupled 111In-pentetreotide. METHODS: Forty patients with Graves' ophthalmopathy, 5 patients with orbital myositis and 10 control subjects were included in this prospective study. Indium-111-pentetreotide (110 MBq) was intravenously injected and SPECT images were obtained at 4 and 24 hr after injection. The scans were analyzed by a region of interest technique. An uptake ratio between the orbits and the brain was determined. RESULTS: Compared to controls (4-hr 111In-pentetreotide uptake: median 6.0 counts/voxel/MBq, orbit-to-brain ratio 5.6), ophthalmopathy patients showed two- to threefold increased uptake (15.8 counts/voxel/MBq versus controls p = 0.0032; ratio 12.6 versus controls p = 0.003). When considering patients with active disease only, even higher uptake was registered (16.8 counts/voxel/MBq versus controls p = 0.0048, ratio 15.6 versus controls p = 0.0006). Untreated patients showed markedly higher uptake (23 counts/voxel/MBq) compared to patients under steroid therapy (12.6, p = 0.001). In myositis, high uptake (20 counts/voxel/MBq) was also registered. CONCLUSION: In contrast to controls, ophthalmopathy patients showed markedly increased orbital accumulation of labeled 111In-pentetreotide. This sensitive nuclear medicine technique could possibly select those patients who might benefit from treatment with immunosuppressive agents and/or octreotide.

Eye↗

[A new method for early detection of neurotoxic diseases (exemplified by pyrethroid poisoning)].

This pilot-study should contribute to the question whether Pyrethroid intoxication can be distinguished from other diseases by characteristic clinical symptoms. The results show that the characteristics of the intoxication do not consist in singular symptoms but in combinations and correlations of symptoms, i.e. of central-neurological with peripheral- and autonomic-neurological as well as with characteristic immunological disturbances. Neurological symptoms consist in cerebro-organic disfunctions, locomotory disorders reminiscent of multiple sclerosis or M. Parkinson, and sensory, motoric and vegetative polyneuropathy, leading, for instance, to cardiovascular regulatory disorder like sympathicotonia or, orthostatic hypotonia. Non-neurological symptoms include immunosuppression with consecutive opportunistic infections, like candida albicans, most frequently of the alimentary tract, but also dermal and mucosal swellings, lichen-ruber-like efflorescences, loss of hair, conjunctivitis. Other symptoms are: hypoglycaemic crises inhibition of fertility, disturbances of blood clotting, and most frequently in children, suspected hematopoetic disorders.

Adult↗

The librarian as a partner in nursing education.

Welch Medical Library has explored new roles for librarians in knowledge management instruction programs throughout the Johns Hopkins University School of Nursing curricula. These programs have created roles for library staff as both instructors and knowledge management experts. By fostering strong communication and attention to quality instruction, librarians achieved their vision of a program in knowledge management integrated into the curriculum, where they are partners working with nursing faculty to define the students' knowledge management needs and decide how these needs can be met.

Baltimore↗

Pathogen-defence gene prp1-1 from potato encodes an auxin-responsive glutathione S-transferase.

Genetic studies have previously implicated the prp1 gene family in the defence of potato against infection with the late blight fungus Phytophthora infestans. Here, we show that the concentrations of PRP1 mRNA as well as protein rapidly increase in potato leaves after fungal infection and stay at high levels during an extended period of the infection cycle. After separation of subcellular components by differential centrifugation, PRP1 protein was identified in the cytosolic fraction. Expression studies with chimeric promoter/beta-glucuronidase gene constructs in transgenic potato plants provided evidence that transcription of the prp1-1 gene, representing one member of the prp1 gene family, is at least partly responsible for the accumulation of PRP1 mRNA and protein upon fungal infection. After expression of the prp1-1-coding sequence in Escherichia coli, the corresponding 26-kDa protein exhibited glutathione S-transferase activity with Km values of 9.8 mM and 0.11 mM for the artificial standard substrate 1-chloro-2,4-dinitrobenzene and glutathione, respectively. Photoaffinity labeling of the protein with tritiated 5-azido-indole-3-acetic acid suggested that the phytohormone indole-3-acetic acid or a structurally related compound serve as a regulator or substrate of the prp1-1 encoded glutathione S-transferase. This assumption was further supported by the inhibitory effect of the phytohormone on the enzyme activity in vitro. The implications of these findings for a potential involvement of indole-3-acetic acid in the control of defence reactions are discussed.

Affinity Labels↗

Extreme stability of Tyr-MIF-1 in CSF.

Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), an endogenous brain peptide, was incubated at 37 degrees C in cerebrospinal fluid (CSF) from rats and the amount remaining in intact from determined by high performance liquid chromatography (HPLC). By 3 min, a time at which Tyr-MIF-1 had been considerably degraded by rat plasma, essentially no degradation of the tetrapeptide had occurred in CSF. Tyr-MIF-1 persisted in mainly intact form for the 8 days tested, with a calculated half-time degradation of 11.4 days. The simultaneous addition to CSF of equal amounts of Tyr-MIF-1 tritiated on the Tyr and Tyr-MIF-1 tritiated on the Pro facilitated determination of whether Tyr-MIF-1 serves as a precursor of MIF-1 (Pro-Leu-Gly-NH2) in CSF. This possibility was excluded by the findings that the primary metabolite was Tyr-Pro, with minimal and equal amounts of the free amino acids Pro and Tyr being formed, but no MIF-1. The results show the extreme stability of Tyr-MIF-1 in CSF and are consistent with a role for this peptide in the CNS.

Amino Acid Sequence↗

Differential metabolism of Tyr-MIF-1 and MIF-1 in rat and human plasma.

The metabolism of the endogenous brain peptides Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and MIF-1 (Pro-Leu-Gly-NH2) was determined by HPLC after incubation of the tritiated peptides in human and rat plasma. Degradation of Tyr-MIF-1 was rapid in the plasma from both species, in contrast to the slightly delayed degradation of MIF-1 in rat plasma and the extremely prolonged persistence of MIF-1 in human plasma. In rat plasma, more than half of the intact Tyr-MIF-1 and MIF-1 was degraded within 5 min, in contrast to the 5 days required for 50% degradation of MIF-1 in human plasma at 37 degrees. To slow the rapid rate of metabolism, studies were then performed at 0 degree. Incubation of Tyr-MIF-1 in human plasma at 0 degree for 2 hr resulted in HPLC identification of more Tyr-Pro than Tyr at all times. At 0 degree in rat plasma, however, more Tyr than Tyr-Pro was formed after the first 5 min of incubation of the Tyr-MIF-1 that was labeled on the Tyr. This raised the possibility that the tetrapeptide Tyr-MIF-1 might be serving as a precursor of the tripeptide MIF-1. Incubation of Tyr-MIF-1 tritiated at the Pro under the same conditions with and without Tyr-MIF-1 tritiated at the Tyr showed that Tyr-Pro, not MIF-1, was the predominant degradation product of Tyr-MIF-1. In addition to the metabolism of Tyr-MIF-1 being slower at lower temperatures, it was also slowed by some enzyme inhibitors. After 10 min of incubation at 37 degrees, EDTA appeared to be more effective than bestatin, p-chloromercuribenzoic acid (PCMB), pepstatin, or aprotinin, but after 30 min, bestatin was more effective. Intravenous injection of the tritiated peptides into rats showed short half-time disappearances; again, MIF-1 persisted in blood longer than Tyr-MIF-1. Thus, the results show the rapid metabolism of Tyr-MIF-1 in human and rat plasma, the slightly slower metabolism of MIF-1 in rat plasma, the predominant formation of Tyr-Pro rather than MIF-1 from Tyr-MIF-1, and the markedly delayed metabolism of MIF-1 in human plasma.

Amino Acid Sequence↗

Antigen presentation and cytotoxic T lymphocyte killing studied in individual, living cells.

Interactions between individual, living fibroblasts and cytotoxic T lymphocyte (CTL) clones were analyzed by using video-enhanced differential interference contrast and fluorescence microscopy in a multimode configuration. Fibroblasts expressing known major histocompatibility complex I alleles (MC57: H-2b; Balb: H-2d) were sensitized for killing by incubating or microinjecting them with peptide fragments of lymphocytic choriomeningitis virus. Previous determination of the CTL clones' specificity for these peptides and MHC-I alleles enabled us to study CTL killing of fibroblasts, and nonlethal CTL interaction with targets due to "mismatches" of the CTL, target, and/or peptide. During viral peptide-specific MHC-restricted CTL killing, distinct morphological alterations were observed (CTL shape changes, movements of granules in CTL cytoplasm, and target cell contraction and blebbing). When no killing occurred, CTL engaged in prolonged, nonrandom movement on the target cells. Alloreactive and virus-specific CTL displayed the same morphology during killing. To study antigen presentation further within individual, living cells, a LCMV glycoprotein peptide (aa 272-286, LSDSSGVENPGGYCL) was covalently labeled with tetramethylrhodamine. In 51Cr release assays, the labeled peptide specifically induced potent CTL killing, but neither labeled nor unlabeled peptide proved toxic for unsensitized targets. Microinjection of the labeled peptide into the cytoplasm of fibroblast cells led to CTL killing of those cells, yet nearby uninjected cells contacted by CTL were not killed, indicating that killing was due to presentation of microinjected peptide rather than binding of extracellular peptide to cell surface MHC. Peptide-injected target cells were killed only when combined with CTL specific for the peptide and for the MHC allele of the injected cell.

Amino Acid Sequence↗

Decreased benzodiazepine receptor binding in panic disorder measured by IOMAZENIL-SPECT. A preliminary report.

Single photon emission tomography (SPECT) imaging of the central benzodiazepine receptor (BZr) became possible with the newly developed ligand 123I-IOMAZENIL. The BZr binding was investigated in ten patients with panic disorder (PP) compared to ten epileptic patients (EP). Panic patients had lower IOMAZENIL uptake rates in the frontal, occipital and temporal cortex than EP indicating the involvement of the BZr complex in panic disorder.

Adult↗

Delayed degradation of Tyr-MIF-1 in neonatal rat plasma.

Peptides like Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) that are administered during the neonatal period can result in biological effects persisting into the adult period. The possibility that Tyr-MIF-1 might have a prolonged half-life in neonatal blood was investigated by HPLC of plasma obtained from 4-day-old rat pups. More than half (65%) of the tritiated Tyr-MIF-1 incubated with neonatal rat plasma at 37 degrees C remained in intact form at 30 min compared with less than a quarter of the Tyr-MIF-1 incubated with adult rat plasma. The calculated half-life of the tetrapeptide incubated in neonatal plasma was 50.2 min, compared with 13.8 min for adult plasma (p < 0.01). The simultaneous addition of Tyr-MIF-1 tritiated on the Tyr and Tyr-MIF-1 tritiated on the Pro showed the formation of equal amounts of the free amino acids Tyr and Pro; this indicates that Tyr-MIF-1 is not a precursor of MIF-1 in neonatal rat plasma. The results show that the degradation of Tyr-MIF-1 is significantly delayed in plasma from neonatal rats, suggesting the possibility that the metabolism of other peptides and different types of compounds also may be delayed during the perinatal period.

Aging↗

[Somatostatin receptor scintigraphy in endocrine orbitopathy].

Somatostatin receptor scintigraphy with 111In-labeled octreotide proves to be a very sensitive diagnostic tool for evaluation of inflammative activity in endocrine ophthalmopathy (EO). The results of somatostatin receptor scintigraphy (SRS) in 40 patients with EO show a high orbital accumulation of 111In-octreotide in clinically active EO (4 h-median/orbit-brain-ratio: 12.6; controls 4 h-median: 5.8) Patients with clinically inactive EO (4 h-median: 7.1) show a similar orbital accumulation of radioactivity compared to controls. 5 patients with active orbital myositis also revealed an even higher orbital accumulation of radioactivity (4 h-median: 42.3). The diagnostic value of SRS lies in its ability to act as a measure of inflammation and can be useful as an activity parameter when planning therapeutic procedure as well as for EO follow-up. The results in patients with orbital myositis nevertheless do not permit a differential diagnosis with this method. The therapeutic value of 111In-octreotide in Graves' disease has yet to be established.

Adult↗

Improving the accuracy of 99Tcm-mercaptoacetyltriglycine clearance by using two blood samples instead of one? Paediatric Task Group of the EANM.

From a database of 133 patients (98 children and 35 adults) who underwent multiple blood sampling for 99Tcm-mercaptoacetyltriglycine (MAG3) clearance, we determined simplified algorithms allowing the estimation of clearance. A one-compartment model with two blood samples was applied. The best choices for the adult population were the 12 and 90 min blood samples, giving a standard error of the estimate (S.E.E.) of less than 10 ml min-1 1.73 m-2; for the children, the 10 and 80 min blood samples gave a S.E.E. of 20 ml min-1 1.73 m-2; for both the adults and the children, the 10 and 70 min blood samples gave the best results with, however, a S.E.E. of 19 ml min-1 1.73 m-2. The use of such a combined algorithm will therefore result in a degradation of the results in adults, suggesting that a separate algorithm for each group is preferable. We compared the accuracy of the two blood sample method to the one blood sample method based on previously published algorithms for children and adults, respectively. The S.E.E. was significantly lower, in adults as well as in children, using the empirical two blood sample method. This two blood sample method seems potentially useful for routine practice in adult patients. The advantages of using such a method in children is balanced by the practical problems inherent in the need to take a second blood sample during the first 10 min, at a time when the plasma activity is rapidly decreasing.

Adult↗

[Radiation exposure from nuclear medicine studies in children].

Nuclear medical examinations of children have to be performed with special regard to the problems of radiation protection because of the high radiation sensitivity esp. of infants and young children. The present contribution describes how any unnecessary radiation exposure can be avoided by the correct choice and planning of a nuclear medical study, by using the appropriate radiopharmaceutical as well as by the exact calculation of the amount of activity applied, depending on body surface resp. body weight of the child. A technically optimized method which employs the best technical equipment and personnel, being specially trained for working with children, are important conditions to achieve optimal results of nuclear medical tests. Due to the difficulties of direct dose measurements, large variations in the biokinetic behaviour of radiopharmaceuticals and the restriction to standard phantoms, individual dose calculations or dose estimations in pediatrics cause great problems. This is reflected by often large variations of dosimetrical data given in the literature.

Adolescent↗

[Scintigraphic display of an ectopic parathyroid adenoma using 99mTc-MIBI--2 case reports].

Radionuclide imaging of the parathyroid gland is used in the preoperative localization of parathyroid adenoma. Until recently radionuclide imaging of parathyroid tumors was performed using a dual-tracer subtraction technique with 201TI and 99mTcO4-. As an alternative radionuclide imaging with 99mTc-sestamibi (MIBI) has been introduced some years ago. The utility of preoperative parathyroid localization lies in its ability to direct surgical exploration, particularly of ectopic localizations. We present two cases of parathyroid adenoma in which radionuclide imaging with 99mTc-MIBI was successful in detecting atypical locations. In the first case remaining primary hyperparathyroidism was caused by a mediastinal gland. The second case suffered from a recurrence of secondary hyperparathyroidism caused by hyperplasia of the autotransplanted gland after removal of all four parathyroid glands.

Adenoma↗

Bird feathers as bioindicators in areas of the German Environmental Specimen Bank--bioaccumulation of mercury in food chains and exogenous deposition of atmospheric pollution with lead and cadmium.

Feathers of selected bird species are used as pollution integrating biomonitors in areas of the German Environmental Specimen Bank. Lead, cadmium and mercury are analysed by Zeeman Solid Sampling AAS in feather vanes of selected bird species with different ecologies. In feather vanes there are quite different distribution patterns of lead and cadmium on the one hand and mercury on the other: lead and cadmium show strong gradients with respect to feather parts with high exposure to atmospheric influences. In contrast to this, mercury is distributed homogeneously. These different distribution patterns of lead and cadmium in feather vanes, in contrast to mercury, show that there are quite different incorporation paths. Cadmium and lead are deposited exogenously and indicate atmospheric pollution. Mercury in feathers is caused endogenously by food and physiology. Most of the mercury analysed in bird's feathers is in the ecotoxic methylated form and the contents in feathers depend on bioaccumulation in food chains. Feathers are suitable indicators for monitoring heavy metal pollution and give us information about incorporation paths and ecotoxic effects.

Aging↗

Determination of the technetium-99m mercaptoacetyltriglycine plasma clearance in children by means of a single blood sample: a multicentre study. The Paediatric Task Group of the EANM.

A multicentre European study was undertaken in order to determine a reasonable algorithm allowing the determination of overall technetium-99m mercaptoacetyltriglycine clearance using a single blood sample. Employing multiple blood sample clearance as a reference method, it was shown that an acceptable estimation of the MAG3 renal clearance could be obtained using a blood sample taken at any time between 30 and 40 min after tracer injection. After correction for body surface area, comparison of clearance determined using (a) the single blood sample and (b) the multiple blood samples provided a coefficient of correlation of 0.949 and an SEE of 27 ml/min. This algorithm is valid for clearance values higher than 100 ml/min/1.73 m2 and for children older than 1 year of age.

Algorithms↗

The value of nuclear medicine for the diagnosis of spine diseases.

Nuclear medicine examinations hold an important position in the diagnosis of diseases of the spine. During the last decade, decisive progress has been made in the field of instrumentation and radiopharmaceutical techniques: the use of high resolution collimators and the introduction of emission computer tomography as examples of improved instrumentation as well as 99m-Technetium red blood cell labelling as a new radiopharmaceutical technique. These present some of the developments responsible for the growing importance of scintigraphical diagnosis. Inflammatory processes of the vertebrae and the surrounding soft tissues can be detected or excluded with high reliability by the use of radionuclide-labelled granulocytes. The important role of bone scintigraphy in the differential diagnosis of neoplastic bone disease relies on its high sensitivity combined with the quantitative analysis of increased bone metabolism. Furthermore, it provides exact information about the extent and a possible metastatic spread of bone tumours. In the field of orthopaedy and surgery, skeletal scintigraphy is of growing importance as a highly sensitive procedure in the detection of special traumatic lesions such as acute vertebral compression fractures and in the follow-up of patients after bone surgical interventions. Despite the progress of other imaging modalities such as computer tomography and magnetic resonance imaging, nuclear medicine today is well-established in the assessment of diseases of the vertebral column. Among all scintigraphical diagnostic procedures, bone scintigraphy and the different techniques of inflammation imaging are of special importance.

Adult↗