Hans Karle

Receptor binding of lactoferrin by human monocytes

Summary. The binding of iron‐saturated 125I‐lactoferrin to human monocytes was studied at pH 7·4 and 37°C. Monocytes in suspension bound 125I‐lactoferrin by a reversible, saturable and specific binding indicating the presence of a receptor. The dissociation constant (KD) of the binding was estimated at about 4·5 × 10−9 M and the number of receptors was about 1·6 × 106 per monocyte. The affinity of native lactoferrin (20% iron saturated) was only slightly below that of iron‐saturated lactoferrin (KD about 7·9 × 10−9 M). Human transferrin, horse cytochrome c and human immunoglobulin G were without inhibitory effect on the binding of 125I‐lactoferrin. The majority of cell‐bound 125I‐lactoferrin was dissociable. The dissociation rate was not affected by addition of unlabelled lactoferrin to the dissociation medium. The binding of 125I‐lactoferrin to adherent mononuclear blood cells showed an about 100‐fold lower affinity (KD about 2·5 × 10−7 M) than to cells in suspension, but the specificity of the binding was the same. These results are compatible with the idea that lactoferrin exerts a biological effect mediated by an interaction with cells of the monocyte/macrophage lineage.

Lysozyme turnover in man.

Lysozyme turnover studies with (125)I-labeled human lysozyme were carried out on 22 patients, viz. nine control patients, seven nephrological patients with varying degrees of renal insufficiency, including three bilaterally nephrectomized patients, and six hematological patients with disturbed turnover of the neutrophilic granulocytes. It was found that plasma lysozyme has a rapid turnover with a fractional catabolic rate of 76%/hr of the plasma content. Lysozyme catabolism varied with the endogenous creatinine clearance; in addition however, extrarenal sites of catabolism were demonstrated since lysozyme could be broken down in the anephric patients, although only at a rate amounting to about 15% of the rate found in persons with intact kidneys. In the uremic patients the increased plasma lysozyme concentration was due to decreased rates of catabolism; in the hematological patients the increased plasma lysozyme level was due to increased rates of synthesis which supports the hypothesis that plasma lysozyme mainly stems from disintegrating neutrophilic granulocytes. Furthermore, it was shown that in the nonhematological patients examined, the rate of synthesis varied with the endogenous creatinine clearance.

Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

In vivo tissue characterization by measurement of T1- and T2-relaxation processes is one of the greatest potentials of magnetic resonance imaging (MRI). This may be especially useful in the evaluation of bone marrow disorders as the MRI-signal from bone marrow is not influenced by the overlying osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla. In the patients MRI was done at the time of diagnosis and during follow-up of chemotherapy and related to bone marrow biopsies taken within three days of the MRI. At the time of diagnosis T1-relaxation time was increased two to three times in the patients (range 0.7-3.0 sec.) compared to the controls (range 0.38-0.60 sec.). No significant difference was seen in the T2-relaxation process. In relation to chemotherapy T1 decreased towards the normal range in the patients who obtained complete remission, whereas T1 remained prolonged in the patients who did not respond successfully to the treatment. The results indicate that MRI may be a non-invasive clinically useful tool in the evaluation of acute leukaemia especially as a follow-up control of chemotherapy.

Lactoferrin‐mediated transfer of iron to intracellular ferritin in human monocytes

Interactions of 125I‐59Fe‐lactoferrin with human monocytes were studied. After 4 hours of incubation, the uptake of 59Fe exceeded that of 125I. In dissociation studies the cellular 59Fe‐activity was only partly dissociable during 16 h, whereas the 125I‐activity could be released nearly completely. Disruption of the cells and studies on the cytosolic phase were performed employing gel‐filtration and affinity chromatography. An appreciable amount of lactoferrin was found in the cytosolic phase. About 50% of the cytosolic 59Fe‐activity was bound to ferritin. The results suggest that lactoferrin is internalized into monocytes and that iron is transferred to ferritin. These cellular events may contribute to an understanding of the accumulation of iron in the monocyte/macrophage system observed during inflammatory conditions.

Lysozyme turnover in the rat

Lysozyme turnover in the rat was studied with (125)I-labeled rat lysozyme. It was found that plasma lysozyme has a rapid disappearance rate with a half-life of 75 min. The rate of synthesis was calculated at 3.4 mug/min per 100 g rat. This rate of synthesis was compared with figures from the literature for the turnover rate of neutrophilic granulocytes, and the data were consistent with the concept that disintegrating neutrophils are the main source of plasma lysozyme. The distribution of enzymatic lysozyme activity and of radioactive lysozyme was studied in several organs. Very high enzymatic activity was found in leukocytes as were considerable activities in lungs, kidneys, bone marrow, spleen, and intestine; little enzymatic activity was found in the urine. High radioactive levels as compared with plasma radioactivity were demonstrated only in the kidneys. This indicates that of the organs studied, the kidney is the predominant site of storage and destruction of plasma lysozyme. Lysozyme was found to disappear only slowly from the kidneys over a period of 4 days. The data obtained seem to indicate that lysozyme or a lysozyme degradation product precipitable by trichloroacetic acid was released in small amounts from the kidneys to plasma throughout this period.

International recognition of basic medical education programmes.

Objective  This document aims to formulate a World Federation for Medical Education (WFME) policy and to open debate on the subject on international recognition of basic medical education institutions and programmes.Objective  This document aims to formulate a World Federation for Medical Education (WFME) policy and to open debate on the subject on international recognition of basic medical education institutions and programmes. Methods  We carried out a systematic review of international quality assurance of medical education and recognition methodology, including accreditation procedures and alternative quality assurance methods, with a focus on the role of the WFME in international recognition of basic medical education programmes. Results  In order to further the intentions of the WFME, the Federation will: continue its activity to establish new Global Directories of Health Professions Education Institutions (GDHPEI); set up a planning working group to prepare the work of the international advisory committee for GDHPEI; develop a database of relevant accrediting and recognising agencies; continue its project on the promotion of proper national accreditation; establish a working group to develop principles to be used in the evaluation of medical schools and other health professions education institutions and their programmes for the purpose of international recognition, especially when proper accreditation is not feasible, and work with partners on training programmes for advisors and assessors. Conclusions  The new directory for medical schools, which will include qualitative information about basic medical education programmes, will provide a basis for the meta-recognition of medical schools’ programmes by stimulating the establishment of national accreditation systems and other quality assurance instruments.

Effect on Red Cells of a Small Rise in Temperature: in Vitro Studies

An increased destruction of red cells was previously demonstrated during experimental fever. The present study deals with the changes in red cells produced by extended exposure in vitro to temperatures in the biological range of fever.

LYSOZYME ACTIVITY IN CEREBROSPINAL FLUID

Lysozyme activity was measured in cerebrospinal fluid (CSF) from 114 patients with inflammatory (bacterial and serous meningitis, poly‐radiculitis, encephalitis) and non‐inflammatory (multiple sclerosis, CNS tumors, cerebral vascular diseases) CNS diseases. Highly elevated values were found consistently in patients with bacterial meningitis. Elevated values were found also in patients with encephalitis, poly‐radiculitis, multiple sclerosis and CNS tumors, but a considerable overlapping between these groups and normal controls precludes the use of CSF lysozyme measurements as a diagnostic aid in the latter disease groups. Simultaneous measurements of lysozyme, albumin and IgG in CSF and serum suggested that the mechanism for increased CSF lysozyme values in bacterial meningitis is mainly a breakdown of the blood/brain barrier, whereas the increased CSF lysozyme values in the remaining groups of patients are more likely caused by production of lysozyme by cells within the meninges (neutrophilic granulocytes, monocytes?).

Magnetic resonance imaging of the bone marrow in patients with acute leukemia during and after chemotherapy : changes in T1 relaxation

Twenty-seven patients with acute leukemia were examined at the time of diagnosis with MR imaging and in vivo T1 relaxation time measurements of the hemopoietic bone marrow. A 1.5 T whole body magnetic resonance scanner was used. Twenty of the patients had follow-up examinations in relation to chemotherapy. Bone marrow biopsies from the posterior iliac crest were obtained within a short time interval of all MR examinations. At the time of diagnosis, T1 relaxation times were increased significantly in all the leukemic patients, compared with 24 age-matched controls. A decrease in T1 relaxation time towards or into the normal range was observed in 10 patients who obtained remission. The T1 relaxation time remained prolonged in 6 patients who failed to obtain remission during chemotherapy. Four patients, who obtained remission with concomitant decrease of T1 values towards or into the normal range, also showed prolongation of T1 relaxation time in relation to leukemic relapse. The results indicate that changes observed in T1 relaxation times of the hemopoietic bone marrow in patients with acute leukemia reflect changes in disease activity, and, that serial measurements of T1 values may provide clinically useful information with the possibility for identification of residual disease in regions inaccessible for biopsy.

WFME Global Standards in Medical Education: status and perspectives following the 2003 WFME World Conference

The development of the World Federation for Medical Education (WFME) Global Standards in Medical Education can be viewed as consisting of 3 overlapping phases. The first phase concerned the formulation of the Standards at a time when there were no comprehensive, globally recognised standards. The second phase comprised the piloting and evaluation of the WFME Standards, of which the world conference was a part. Based on the results of this, it is envisaged that, in the third phase, more institutions, countries and regions will become familiar with the Standards and further application and refinement will take place as feedback is received. This may also lead to formal recognition or accreditation of medical schools by the WFME. As part of the evaluation process, the WFME organised a world conference, Global Standards in Medical Education for Better Health Care , in March 2003. In a remarkable example of international collaboration, the conference strongly endorsed the evaluation process and encouraged its continuation and the updating of the Standards in the light of further experience.