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Biomedical subjects

H Hartmann

Publications and source records attributed to H Hartmann.

At least 109 records · Page 6Linked to original sources

[Evaluation of hypoxic conditions in calves using the erythrocyte density test (EDT)].

The erythrocyte density separation test (EDT) divides the red blood cells into two groups: younger (less dense) and older (more dense) erythrocytes. Using this test enables veterinarians to assess the erythropoiesis in calves on the basis of the percentage of less dense (younger) red blood cells. Anemic calves, as well as those with pneumonic infections show higher proportions of less dense red blood cells in the EDT than healthy ones. This testing procedure makes it possible to estimate the effects of an oxygen deficiency condition, such as hypoxemia, anemia, shock etc. on the peripheral tissues. So the EDT represents a valuable complement to existing hematological laboratory methods. Carrying out the EDT is very simple and suitable in routine clinical testing.

Anemia↗

[Current therapeutic strategies for hepatocellular carcinoma, 2].

Therapeutic decisions depend on the tumor stage and the functional reserve of the tumor-free liver since most HCC are found in cirrhotic livers. Prospective randomized trials are not available, as is a uniform stage-adapted therapeutic concept. The only potentially curative therapy is surgical. Only 15-30% of patients are suitable for liver resection; localized but anatomically or functionally irresectable tumors can be treated by liver transplantation. Both methods have shown a high recurrence rate; controlled studies on adjuvant therapy are missing. Percutaneous ethanol injection therapy is an alternative in early stages resulting in survival rates comparable to surgical resection. More advanced tumors can be treated by transarterial chemoembolization using Lipiodol. Chemotherapy is little successful, the standard substance Adriamycin achieving remission rates of about 20%. To improve the results of chemotherapy, a combination of cytostatic agents with Lipiodol in non-metastasized tumors has been proposed. Among new therapeutic options such as treatment with cytokines, hormone antagonists, lipiodol or antibodies coupled with radioactivity no definite results have been published so far. Therefore, all patients with HCC should be treated in prospectively controlled, randomized studies.

Carcinoma, Hepatocellular↗

[Portal hypertension--pathophysiology and therapeutic approaches].

The following review article describes pathophysiological aspects of portal hypertension in its first part, especially the topographic variety of the vascular collateral system creating the danger of variceal bleeding. The second part discusses different forms of therapy including pharmaco- and sclerotherapy as well as operative and interventional procedures. Beta-blocker-therapy preferentially serves for the primary and secondary prevention of variceal bleeding. Sclerotherapy appears as the dominant therapeutic tool for the management of acute variceal bleeding. New chances of therapy include variceal banding and the implantation of a transjugular intrahepatic portosystemic stent-shunt (TIPSS). Operative procedure loose their significance more and more by the wide-spread use of sclerotherapy and the chance of a definite therapy of portal hypertension (liver transplantation) and the use of nonoperative interventional procedure (TIPSS or TIPS) which are still under clinical investigation.

Adrenergic beta-Antagonists↗

[Diagnostic and pathophysiological aspects of the determination of kidney function in animals].

Early diagnosis of loss in renal function (< 60-70%) is not possible either by resorting to the parameters of plasma urea and creatinine concentrations (responsive to functional loss by > 75% or by reference to urine concentration capacity (urine density: sensitive to concentrations > 60%). However, clearance techniques for determination of the glomerular filtration rate (GFR) have proved suitable for quantitative assessment of renal function. Endogenous creatinine clearance is one of the most common clinical approaches in GFR determination. Criticism of results obtainable from endogenous creatinine clearance appears to be justified by pharmacokinetic aspects of creatinine as an indicator, as well as by some of its analytical peculiarities. The tediousness of the procedure is another counterproductive aspect pertaining to large-scale use of endogenous creatinine clearance in veterinary medicine. Total blood-plasma clearance of exogenous creatinine (T-Clexo.Creatinine) would provide vets with an accurate (diagnostic validity) and practical method for carrying out clinical kidney-function diagnostics. However, more research on a number of related issues will be required before the general introduction of the procedure.

Animals↗

Rapid quantification of C3a and C5a using a combination of chromatographic and immunoassay procedures.

Monoclonal antibodies were isolated which reacted specifically with the complement cleavage products C3a, C3adR, C5a, and C5adR but not with the parent molecules C3 or C5. In both cases the mAbs showed a higher affinity towards the desArg forms. These mAbs were used as capture antibodies in immunoassays for C3a/C3adR and C5a/C5adR. The immunoassays are based on the ABICAP technology which ensures for a rapid measurement. Due to the large binding capacity and the very short diffusion pathways in the gel-matrix the binding equilibrium between capture antibodies and the antigen is reached whilst the sample is flowing through the column. Therefore this test represents an endpoint assay offering the possibility of using a single calibration curve for a large number of measurements. With the C3adR assay concentrations down to 16 ng/ml C3adR can be detected. The lower detection limit of the C5adR assay is 1 ng/ml C5adR. The tests for C3a/C3adR, and C5a/C5adR can be performed in 20 to 25 min and this rapid processing of plasma samples should permit the application of these parameters for diagnostic purposes and patient management.

Amino Acid Sequence↗

Age-related changes in receptor-mediated and depolarization-induced phosphatidylinositol turnover in mouse brain.

The effect of aging on receptor- and G-protein-activated and on depolarization-induced phosphoinositide (PI) hydrolysis was examined in mechanically dissociated neurons from female NMRI mice. Additionally, age-dependent changes in Ca2+ homeostasis, i.e. changes in basal intracellular calcium ([Ca2+]i) and in depolarization-induced rise in [Ca2+]i were investigated. No age-related differences in PI hydrolysis were found after stimulation of muscarinic cholinergic, alpha 1, serotonin and quisqualate receptors coupled to the phosphoinositide-phospholipase C (PI-PLC) system. PI hydrolysis following stimulation with AMPA ((RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) revealed a significantly increased response in aged animals. Activation of G-proteins with NaF also induced a higher inositol monophosphate (InsP1) accumulation in aged mice. Moreover, InsP1 accumulation due to PLC activation by increased [Ca2+]i after depolarization with KCl was significantly increased in neurons from aged animals. Investigations about age-related changes in Ca2+ homeostasis revealed lower basal [Ca2+]i and lower rise in [Ca2+]i after depolarization with KCl. The data indicate that receptor-mediated and depolarization-induced PI hydrolysis are differentially affected by aging. Decreased availability of [Ca2+]i in aged animals may enhance the sensitivity of Ca(2+)-activated mechanisms. This may explain increased KCl- and AMPA-induced InsP1 accumulation whereas receptor-coupled PLC activation is less affected.

Aging↗

beta-Amyloid protein enhances the mitogen-induced calcium response in circulating human lymphocytes.

The role of beta-amyloid in Alzheimer's disease and its cellular mechanism of action on neurons are still unclear. There is growing evidence that beta-amyloid or its fragment, 25-35, influence neuronal calcium regulation. To investigate the effects of beta-amyloid on calcium homeostasis in man we used peripheral human lymphocytes as a model system for central neurons. beta-Amyloid fragment 25-35 exposed to lymphocytes for 60 s elevates the phytohemagglutinin (PHA)-induced Ca2+ rise in a dose-dependent manner. Small effects were already seen at concentrations as low as 50 nmol/l. Similar effects were also observed with fragment 1-40, whereas fragments 1-28 or 12-28 did not affect the Ca2+ response after PHA stimulation. Our findings support the hypothesis of an enhanced calcium response as a general feature of beta-amyloid's neurotoxicity. The lymphocyte seems to be a valuable model to study this effect in man.

Adult↗

beta-Amyloid protein amplifies calcium signalling in central neurons from the adult mouse.

The role of beta-amyloid in Alzheimer's disease and its cellular mechanism of action are still unclear. Based on observations that beta-amyloid influences neuronal calcium homeostasis we investigated the effect of the peptide on K(+)-induced enhancement of free intracellular calcium in dissociated neurons from adult mice. Preincubation with beta-amyloid fragment 25-35 at concentrations > or = 0.05 mumol/l resulted in marked amplification of the K(+)-induced Ca2+ response. This effect was also observed with fragment 1-40, whereas fragment 1-28 or 12-28 did not affect the Ca2+ response. This preparation therefore presents a valuable model to investigate the action of beta-amyloid ex vivo in individual animals. Our findings suggest a small but consisting destabilizating effect of beta-amyloid on neuronal Ca2+ homeostasis resulting in chronically increased neuronal vulnerability.

Amyloid beta-Peptides↗

Aging enhances the calcium sensitivity of central neurons of the mouse as an adaptive response to reduced free intracellular calcium.

Age-related changes in Ca(2+)-homeostasis have been investigated in mechanically dissociated neurons from young and aged mice. In aged animals, basal intracellular calcium ([Ca2+]i) was significantly reduced and depolarization (KCl)-induced rise in [Ca2+]i was lower, probably as a result of increased activation of Ca(2+)-dependent mechanisms terminating Ca2+ influx. Additionally, depolarization-induced inositol-phosphate (IP) accumulation in aged animals was found to be significantly increased. Both findings suggest that Ca(2+)-dependent intracellular processes become more sensitive to Ca2+ in aged animals due to decreased Ca2+ availability.

Aging↗

Diagnosis and management after life threatening events in infants and young children who received cardiopulmonary resuscitation.

OBJECTIVE: To determine the mechanisms and thereby appropriate management for apparent life threatening events treated with cardiopulmonary resuscitation in infants and young children. DESIGN: Prospective clinical and physiological study. SETTING: Royal Brompton Hospital or in patients' homes, or both. SUBJECTS: 157 Patients referred at median age 2.8 months (range 1 week to 96 months), 111 (71%) had recurrent events, 44 were born preterm, 19 were siblings of infants who had died suddenly and unexpectedly, and 18 were over 12 months old. INTERVENTIONS: Multichannel physiological recordings, including oxygenation, in hospital (n = 150) and at home (n = 61). Additional recordings with electroencephalogram, video, or other respiratory measures were used to confirm diagnoses. Management involved monitoring of oxygen at home, additional inspired oxygen, anticonvulsant treatment, or child protection procedures. MAIN OUTCOME MEASURES: Abnormalities on recordings compared to published normal data and their correlation with clinical events; sudden death. RESULTS: 53 of 150 patients had abnormalities of oxygenation on hospital recordings, 28 of whom had an accompanying clinical event. Home recordings produced physiological data from 34 of 61 patients during subsequent clinical events. Final diagnoses were reached in 77 patients: deliberate suffocation by a parent (18), hypoxaemia induced by epileptic seizure (10), fabricated history and data (Munchausen syndrome by proxy; seven), acute hypoxaemia of probable respiratory origin (40), and changes in peripheral perfusion and skin colour without hypoxaemia (two). Four patients died: three suddenly and unexpectedly (none on home oxygen monitors) and one from pneumonia. CONCLUSIONS: Identification of mechanisms is essential to the appropriate management of infants with apparent life threatening events.

Cardiopulmonary Resuscitation↗

Immunologically unrelated Heliothis sp. and Spodoptera sp. midgut membrane-proteins bind Bacillus thuringiensis CryIA(b) delta-endotoxin.

The Bacillus thuringiensis toxins, CryIA(a), CryIA(b), CryIA(c) and CryIC were used in a ligand-blot assay to detect specific toxin-binding proteins in the brush-border membranes of Heliothis virescens, Helicoverpa zea, Spodoptera littoralis, Spodoptera exigua and Spodoptera litura. While CryIA(a) and CryIA(b) always recognize the same protein(s) in a given species, CryIA(c) and CryIC were found to bind to other proteins. Polyclonal antibodies directed against the CryIA(b) binding protein of H. virescens and polyclonal anti-idiotype antibodies recognizing some determinants of the CryIA(b)-binding protein involved in the interaction with the toxin, were used to analyse immunological relationships among the toxin-binding proteins. The results showed that the 170-kDa toxin-binding proteins from the H. virescens and H. zea are immunologically related. However, the toxin-binding proteins from the Spodoptera species did not cross-react with either type of antibodies. Therefore, we conclude that the CryIA(b) toxin has different binding determinants on the toxin molecules itself which can interact with specific binding sites on the toxin-binding proteins from Heliothis sp. and Spodoptera sp.

Animals↗

The heat shock cognate protein from Dictyostelium affects actin polymerization through interaction with the actin-binding protein cap32/34.

During isolation of the F-actin capping protein cap32/34 from Dictyostelium discoideum, a 70 kDa protein was copurified which by cloning and sequencing was identified as a heat shock cognate protein (hsc70). This protein exhibited a specific and MgATP-dependent interaction with the heterodimeric capping protein. To investigate the protein-protein interaction in vitro, we expressed all three polypeptides separately in Escherichia coli and performed reconstitution experiments of complete or truncated hsc70 with the 32 and 34 kDa subunits of the capping protein. Viscosity measurements and studies on the polymerization kinetics of pyrene-labeled actin showed that hsc70 increased the capping activity of cap32/34 up to 10-fold, whereas hsc70 alone had no effect on actin polymerization. In addition, hsc70 acted as a molecular chaperone by stimulating the refolding of the denatured 32 and 34 kDa subunits of the capping protein. To study the interaction of the two domains of hsc70 with cap32/34, the N-terminal 42 kDa ATPase region and the C-terminal 30 kDa tail of hsc70 were expressed separately in E. coli. The 32 and 34 kDa subunits were capable of associating with both domains of hsc70. The ATPase domain of hsc70, which is structurally related to actin, proved to be responsible for the increased capping activity of cap32/34, whereas the C-terminal tail of hsc70 was involved in folding of the subunits of cap32/34. Our data indicate a novel linkage between 70 kDa heat shock proteins and the actin cytoskeleton.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Acute metabolic actions of des-(B27-B30)-insulin and related analogues in adult rats.

Metabolic potencies of the destetrapeptide insulin analogues des-(B27-B30)-insulin, des-(B27-B30)-insulin-B26-amide, [ThrB26] des-(B27-B30)-insulin-B26-amide and [GluB26] des-(B27-B30)-insulin-B26-amide were studied in anaesthetized adult rats and in primary cultures of rat hepatocytes and compared with that of the native hormone. Hypoglycaemic effects following intravenous bolus injection of insulin or analogues were similar, as were the stimulatory actions on total body glucose disposal during euglycaemic clamping. In these latter studies a maximal stimulation in the range 16-20 mg glucose/kg per hour was observed and identical half-maximally effective serum concentrations for all peptides of about 1 pmol/ml were obtained. Analogue actions on individual peripheral tissues estimated by the uptake of 2-deoxyglucose were not different from those of insulin. In hepatocyte cultures the stimulatory action of destetrapeptide analogues on glycogenesis and on aminoisobutyric acid transport was indistinguishable from that of native insulin, with identical half-maximally effective concentrations. These data demonstrate that des-(B27-B30)-insulin and related destetrapeptide analogues have high biological activity. Since the truncated non-amidated analogue appeared to be monomeric in solution, this peptide could be a candidate for an insulin preparation potentially showing rapid absorption from subcutaneous tissue.

Aminoisobutyric Acids↗