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Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 145 records · Page 8Linked to original sources

Melatonin and deprivation myopia in chickens.

Chicken eyes elongate and become myopic if they are covered with translucent diffusors which degrade the retinal image ('deprivation myopia'). Since it has been shown that dopamine D2/D4 receptors (which mediate inhibition of melatonin synthesis) are also implicated in deprivation myopia, we have studied the role of melatonin in the visual control of eye growth. We have found that (1) diurnal melatonin rhythms and melatonin content in the retina are unchanged during deprivation myopia development despite the breakdown of both diurnal growth rhythms of the eye and diurnal rhythms in retinal dopamine metabolism, (2) diurnal melatonin rhythms and melatonin content in the retina remain unchanged after application of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and presumably also after 6-hydroxydopamine (6-OHDA) application which both have a suppressive effect on deprivation myopia and (3) deprivation myopia was slightly reduced in both eyes after unilateral intravitreal injection of melatonin, despite that deprivation myopia is based on a mechanism intrinsic to the eye. We conclude that melatonin is not involved in the retinal signaling pathway translating visual experience to deprivation myopia.

5,7-Dihydroxytryptamine↗

The C terminal tail of the histamine H2 receptor contains positive and negative signals important for signal transduction and receptor down-regulation.

To examine the role of the C terminal tail in H2 receptor regulation, three cDNAs, encoding truncated histamine H2 receptor mutants (H2T295, H2T307, and H2T341), were constructed and stably transfected in Chinese hamster ovary (CHO) cells. The amino acids before position 307 appear to be necessary for proper receptor transport or folding, as no detectable H2 receptor binding of the H2T295 was observed after transfection. Truncation of the C terminal tail by 51 amino acids (H2T307) did not affect the binding properties of H2 antagonists and histamine or histamine-induced signaling. Yet, removal of 17 amino acids generated a mutant receptor (H2T341), which was able to form a ternary complex but was unable to fully activate the Gs protein on histamine exposure. Agonist-induced but not the cyclic AMP-dependent H2 receptor down-regulation was more profound for the H2T307 receptor, indicating that different structural elements of the H2 receptor protein are involved in the cyclic AMP-dependent and independent pathways of H2 receptor down-regulation. Taken together, in this study we identified regions in the C terminal tail of the H2 receptor that act as positive and/or negative signals in H2 receptor signaling and down-regulation.

Amino Acid Sequence↗

The cell surface marker phenotype of macrophages from HIV-1-infected subjects reflects an IL-10-Enriched and IFN-gamma-deprived donor environment.

T cells depend on costimulation by accessory cells for an immune response. Costimulatory macrophage activity involves the expression of B7 molecules whose expression is upregulated by interferon-gamma (IFN-gamma) and downregulated by interleukin-10 (IL-10). The expression of low-affinity Fc gamma IIIR (CD16), in contrast, is upregulated in the presence of IL-10 and downregulated in the presence of IFN-gamma. In human immunodeficiency virus-1 (HIV-1) infection, the balance between IFN-gamma and IL-10 expression shifts toward IL-10 predominance. Herein, we compare B7 and CD16 macrophage phenotypes from healthy and from HIV-1-infected patients. Patient macrophages express B7 molecules in lower density than macrophages from healthy donors and are resistant to the upregulation of costimulatory molecule expression. B7 expression can be normalized in patient macrophages by treating them with anti IL-10 monoclonal antibodies (mAb) and IFN-gamma together but not by treatment with either anti-IL-10 mAb or IFN-gamma alone. This finding suggests an excess of IL-10 in HIV-1 infection and an IFN-gamma deficiency, consistent with previous cytokine assessments in HIV-1-infected subjects. The upregulation of CD16 expression was readily induced in patient macrophages by treatment with IL-10 and was inhibited by treatment with IFN-gamma. CD16 expression identifies the subset of cytotoxic macrophages that has been shown to destroy CD4T cells, which they target through CD4-reactive immune-complexed HIV-1 envelope molecules.

Acquired Immunodeficiency Syndrome↗

Randomised study assessing the effect of phenytoin and magnesium sulphate on maternal cerebral circulation in eclampsia using transcranial Doppler ultrasound.

OBJECTIVE: To assess maternal middle cerebral artery flow velocity patterns as measured by transcranial Doppler ultrasound (TCD) in eclampsia and to investigate the effect of the anticonvulsants magnesium sulphate (MgSO4) and phenytoin on cerebral circulation. DESIGN: Prospective randomised study. SETTING: High care obstetric unit, King Edward VIII Hospital, Durban, South Africa. PARTICIPANTS: Twenty-four eclamptic patients: 13 received MgSO4 and 11 phenytoin. INTERVENTION: Middle cerebral artery flow velocity waveforms were measured using 2 MHz pulsed Doppler ultrasound via the transtemporal approach in eclamptic patients, before and 15 minutes after the loading dose of anticonvulsant. RESULTS: Magnesium sulphate significantly reduced the pulsatility index (P = 0.002) and mean flow velocity (P = 0.02) in the middle cerebral artery, whereas phenytoin failed to produce any statistically significant effect. However, differences between groups were not statistically significant. Systolic and diastolic blood pressures were reduced in both the MgSO4 and phenytoin groups. CONCLUSION: These findings provide firm evidence that MgSO4 relieves cerebral vasospasm, compared with phenytoin, and may therefore be the better drug for the prevention of eclamptic convulsion.

Adolescent↗

Cell-matrix interactions of normal and transformed human keratinocytes in vitro are modulated by the synthetic phospholipid analogue hexadecylphosphocholine.

We have investigated the effect of the synthetic phospholipid analogue, hexadecylphosphocholine (HePC), a member of a new class of membrane-affecting antiproliferative drugs, on adhesion to extracellular matrix components, reorganization of three-dimensional collagen lattices, and proliferative activity of human keratinocyte populations in vitro. Six transformed keratinocyte lines were compared with their normal counterparts from interfollicular epidermis. Adhesion to collagen types I and IV, laminin, and fibronectin was weakest in normal keratinocytes (binding of 3-10% of the cells), followed by HaCaT and HaCaT-II/3 (25-30% binding), and the squamous carcinoma lines and SV-40 transformed keratinocytes (35-50% binding). Treatment with non-toxic doses of 10-20 mumol/l HePC led to a clear inhibition of the adhesive interactions by 50-75% in all populations. The impaired adhesion capacity was paralleled by a clear decrease of the ability of all keratinocyte populations to contract three-dimensional collagen lattices, an experimental model system for the reorganization of extracellular matrices. Histological examination revealed that these effects were due to a reduced cell number in the collagen lattices, a finding underscored by significant inhibition of proliferative activity of all keratinocyte populations by HePC. Furthermore, HePC led to marked changes of cellular morphology in the contracted gels. FACS analysis revealed that the impaired interaction with components of the extracellular matrix was not due to a specific downregulation of beta 1-integrins, the major cell-surface receptors for the respective matrix proteins. In conclusion, our results provide new insights into the potential action of HePC in a variety of skin disorders. Decreased proliferative activity and changes of cellular morphology, combined with impaired interactions with extracellular matrix proteins and a consecutive loss of matrix organization capacity, may cause suppression of different hyperproliferative skin diseases.

Antineoplastic Agents↗

Comparative results of transluminal extraction coronary atherectomy in saphenous vein graft lesions with and without thrombus.

OBJECTIVES: The purpose of this retrospective study was to compare the results of transluminal extraction coronary atherectomy in saphenous vein graft lesions with and without angiographic thrombus. BACKGROUND: Percutaneous interventions in lesions with thrombus are associated with reduced procedural success and increased risk of complications. Use of the transluminal extraction catheter, which cuts and aspirates atheroma and thrombus, has been advocated as a potential revascularization strategy for lesions with thrombus. METHODS: Baseline patient characteristics, lesion morphology, immediate angiographic results, in-hospital complications and follow-up were prospectively entered into an interventional cardiology data base. The results of transluminal extraction coronary atherectomy in saphenous vein bypass grafts with angiographic thrombus were compared with results in similar grafts without angiographic thrombus. RESULTS: Transluminal extraction coronary atherectomy was performed in 175 patients with 183 vein graft lesions, including 59 lesions (32%) with thrombus (Group 1) and 124 (68%) without thrombus (Group 2). Compared with lesions in Group 2, lesions in Group 1 were associated with a higher incidence of baseline total occlusion, diffuse disease and abnormal Thrombolysis in Myocardial Infarction (TIMI) grade flow (p < 0.05); more severe diameter stenosis at baseline, after atherectomy and after final angiography (p < 0.05); a lower rate of clinical success (69% vs. 88%, p < 0.01); and more angiographic and clinical complications, including no reflow (p < 0.05), vascular repair (p < 0.05) and Q wave myocardial infarction (p = 0.09). CONCLUSIONS: In transluminal extraction coronary atherectomy of saphenous vein bypass grafts, the presence of thrombus is associated with more baseline lesion complexity, reduced clinical success and increased risk of no reflow, Q wave myocardial infarction and vascular repair.

Aged↗

[Chronic treatment refractory osteomyelitis of long tubular bones--possibilities and risks of intramedullary boring].

Osteomyelitis of long bones is a severe complication of fracture healing. If on-going infection occurs despite reoperation and if antibiotic treatment is of no benefit, reaming of the medullary canal has been considered beneficial. We investigated long-term follow-up (minimum 2 years) in patients submitted to reaming of the medullary canal to evaluate the efficacy of this method. Criteria for success were: no recurrence and no further antibiotic treatment necessary. Of 37 patients, 32 were followed up (mean duration after reaming, 3.7 years). The mean number of surgical operations for osteomyelitis prior to reaming was 3.2. In 88% of patients a full range of motion was observed upon reexamination, while in the others stiffness attributable to articular injuries that had been sustained preoperatively was still present. We found that 84.3% of patients were working in the same profession as prior to the fracture, 72% were involved in sport again, and 97% of patients were pain free. One otherwise healthy patient suffering from sclerosing osteitis (Garré) died of bone marrow embolism into the lung during reaming of the femur. Reaming of the medullary canal has a high cure rate in osteomyelitis even after several previous treatment attempts with surgical revision and/or antibiotic medication. The mechanism is most probably based on improvement of local perfusion. During surgery care must be taken not to provoke pulmonary embolization. Intraoperative monitoring by pulmonary artery catheter should be performed; reaming should be discontinued immediately, if a rise in of pulmonary artery pressure occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Meralgia paraesthetica in a body-builder].

The article describes the case of meralgia paraesthetica, a disease not uncommon, of a bodybuilder. Extensive literature of meralgia paraesthetica shows us several reasons for the injury of the lateral cutaneous nerve of the thigh, but the genesis of the nerve-injury by strain in training is unusual. Diagnostics and therapy of that disease do not present any difficulty.

Adult↗

Transcranial Doppler with contrast injection for the detection of patent foramen ovale in stroke patients.

Right-to-left shunt through a patent foramen ovale was searched for in 80 patients with acute ischemic stroke by simultaneously performing transthoracic two-dimensional echocardiography and transcranial Doppler during agitated saline injection. A patent foramen ovale was detected by echocardiography in 14 patients (17.5%). Transcranial Doppler correctly identified all 14 patients, and 7 more patients in whom echocardiographic findings were indeterminate. Prevalence of patent foramen ovale by transcranial Doppler was therefore 26.3% (21 of 80 patients). Concordance between the two tests was 91.3% (73 of 80 patients). The delivery of contrast material to cerebral vessels is therefore demonstrable by transcranial Doppler in all patients diagnosed by contrast echocardiography, suggesting that paradoxical embolization through a patent foramen ovale may be more frequent than previously thought. Transcranial Doppler with contrast injection is a valid alternative in case of poor echocardiographic image quality.

Cerebral Arteries↗

Effect of ACE inhibitors on atrial natriuretic factor in the brains of rats with reduced renal mass.

We tested the effect of renal insufficiency, with and without angiotensin (Ang) converting enzyme (ACE) inhibition, on blood and brain atrial natriuretic factor (ANF) in rats. Two ACEs, one which penetrates into the CNS and one which does not, were used to distinguish between peripheral and central ACE effects. Rats underwent 5/6 nephrectomy (5/6-NPX) by ligation of renal arterial branches. After seven days, 28 5/6-NPX rats received lisinopril 20 mg/kg/day and 28 5/6-NPX rats received quinapril 30 mg/kg/day orally for five days, while 28 5/6-NPX control rats and 28 sham rats did not. Body weight, blood pressure, drinking and urine volume were monitored. At sacrifice, urine, plasma, and brain tissue was collected. ANF in 16 brain areas was measured by radioimmunoassay. 5/6-NPX resulted in increased blood pressure, increased urine volume, proteinuria, and increased drinking. Both ACEs lowered blood pressure to sham values and decreased proteinuria. Both ACEs increased plasma renin activity and decreased plasma ANF. However, only lisinopril decreased drinking and urine volume. 5/6-NPX increased ANF values in six brain areas, namely the periventricular preoptic nucleus, the arcuate nucleus, the perifornical nucleus, the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus compared to sham rats. These same increases in brain ANF were also observed in 5/6-NPX rats given quinapril, compared to shams. However, lisinopril lowered ANF to sham levels in the periventricular preoptic nucleus, the arcuate nucleus, and the perifornical nucleus. In the three additional brain areas, namely the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus, lisinopril did not effect the elevated ANF concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

[Ruminal nitrogen metabolism in calves and sheep. 3. Effect of hay-concentrate ratio in calves].

During the milk feeding period (ca. 55th day of life) and 2 weeks after the milk feeding period (ca. 80th day of life) the influence of a hay quota in the ration (on DM basis) of 6, 10, 14 and 18% in the milk feeding period and of 16, 23, 31 and 37% in the period after milk feeding was tested as to ruminal N metabolization with calves supplied with duodenal re-entrant cannulae. The increase of the hay quota in the ration for ruminating calves reduced as a tendency duodenal NAN passage, its bacterial N-quota, post-ruminal NAN digestibility and, due to a worse utilization of available N for bacterial N-synthesis, bacterial N-synthesis rate. The apparent fermentation of organic matter was, as a tendency, increased with the growing hay quota in the ration.

Animal Feed↗