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Biomedical subjects

W Hartmann

Publications and source records attributed to W Hartmann.

At least 37 records · Page 2Linked to original sources

Results of allogeneic bone marrow transplantation in patients with leukocyte adhesion deficiency.

We have retrospectively analyzed the outcome of bone marrow transplantation (BMT) in 14 patients with leukocyte adhesion deficiency (LAD) performed in two centers between 1981 and 1993. Five patients received BMT from HLA-identical donors. Nine received T-depleted marrow from two HLA antigen- or haplotype-incompatible parents. Conditioning regimen consisted of chemotherapy exclusively in 13 patients and associated with total body irradiation (TBI) in one patient. In five cases, failure of engraftment occurred as a result of either insufficient myeloablation (n = 3) or, possibly, graft rejection in two cases of moderate phenotype of LAD. The second conditioning regimen consisted of TBI and chemotherapy with the use of anti-lymphocyte function-associated antigen 1 (LFA-1) and anti-CD2 monoclonal antibodies for patients with the moderate phenotype of LAD. These patients were successfully retransplanted. Eight patients developed acute graft-versus-host disease (GVHD). Chronic GVHD occurred in five cases. GVHD led to the death of three patients. Ten patients are alive and well 12 months to 12 years after BMT. Chimerism is full in six of these patients and mixed but stable in four with variable proportion of donor leukocytes. One patient with less than 15% donor leukocytes has mild gingivitis, while the others are well. Sequelae from BMT are limited in two cases to growth retardation caused by TBI. Success of BMT in cases of LAD including seven of nine recipients of HLA nonidentical marrow indicates that this procedure can be proposed as a curative approach to LAD regardless of an available HLA-identical donor. Great care should be taken in GVHD prophylaxis and treatment.

Adolescent↗

Late effects of anthracycline therapy in childhood in relation to the function of the heart at rest and under physical stress.

To evaluate the long-term effects of anthracyclines on the myocardium of the young child we examined 34 patients who had been treated with anthracyclines in childhood. In addition to anthracycline, the patients were treated with other potentially cardiotoxic substances within the framework of different protocols. The mean cumulative anthracycline dose was 128.6 mg/m2, the average age at onset of chemotherapy 4.2 years, and the time interval after discontinuation of treatment 9.0 years. The cardiological examination consisted of a physical examination, electrocardiography and echocardiography, including Doppler and bio-impedance cardiography. The patients were studied at rest and after physical exercise with a cycle ergometer test in a supine position. The results of the physical examination, the electrocardiogram at rest and the 24 h Holter monitoring were normal. The left ventricular enddiastolic diameter, shortening fraction, velocity of fibre shortening (VCF), the diastolic flow profile at the mitral valve level and the cardiac stroke volume at rest were also normal. However, the shortening fraction (SF) was below the margin of 2 standard deviations in two patients and the VCF in three patients. There was a significant reduction in septal thickness, (-1.4 SD, P < 0.0004), in the width of left ventricular posterior wall (-1.5 SD, P > 0.0002) and in the left ventricular myocardial mass (-0.76 SD, P = 0.0042). Physical working capacity was normal. Immediately after physical stress the expected rise of SF and VCF did not occur and the SF fell below the values at rest. In comparison to a healthy control group the SF and the VCF were markedly decreased (P > 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

ImmunoMax. A maximized immunohistochemical method for the retrieval and enhancement of hidden antigens.

BACKGROUND: Since the introduction of mAb, immunohistochemistry has become an important tool in research and in surgical pathology. The most widely used fixative in routine histopathology is formaldehyde, and it has become the gold standard for morphologic tissue preservation. Although the molecular mechanism underlying the tissue fixation is not well understood, it has become clear that available immunoreactive Ag are progressively lost during the fixation process. For a long time, it was thought that formalin-sensitive Ag might be irreversibly destroyed during the fixation process. Although monoclonal anti-Ig Ab frequently worked inadequately, polyclonal anti-Ig Ab were shown to produce reproducible staining results. It thus appeared possible that most cellular Ag might not be irreversibly destroyed but only masked. EXPERIMENTAL DESIGN: Although some Ag may be retrieved under appropriate conditions, there might still be many for which available antigenic epitopes are still too sparse to be visualized, as observed for a large number of leukocyte differentiation Ag. One reliable approach to resolve this dilemma is the use of a combination of an optimized Ag retrieval system and a powerful immunohistochemical staining protocol introducing a biotin amplification step, in which signal amplification is accomplished by covalent deposition of biotin molecules. RESULTS: Cryostat and paraffin sections were stained with the avidin-biotin complex technique and, for comparison, with the new maximized immunohistochemical staining protocol, termed the ImmunoMax method. Each step was monitored to establish how effectively it enhanced the overall sensitivity. Although pretreatment with detergent, protease, a chaotropic substance, or microwave heating resulted in only moderately improved immunostaining, the biotinylated tyramine enhancement step proved to be the most efficient one, although the latter is not sufficient for many Ag when used without pretreatment steps. The combination of an Ag retrieval step with the biotinylated tyramine enhancement step resulted in a 100 to 10,000-fold boost in sensitivity without loss of specificity. CONCLUSIONS: With the ImmunoMax method, defined Ag can be reproducibly detected in formalin-fixed, paraffin-embedded tissues, and the sensitivity of the method is tremendously enhanced. Moreover, it also allows many previously unreactive or unsatisfactorily reactive Ag to be detected, as shown here for IgD, IgM, and CD7 with the use of mAb.

Antigens↗

[Bilateral multiple pulmonary coin lesions--adenoid cystic carcinoma of the lung with 14-year follow-up].

The authors report on an adenoid cystic carcinoma (ACC) of the lung that had been discovered by chance 14 years before the death of the patient and that had at first been interpreted morphologically as a metastatic lung or as a bronchioalveolar carcinoma. The patient remained without any complaints for 13 years. Diagnosis of ACC became possible only by means of a renewed peripheral lung biopsy. An extrapulmonary primary tumour was excluded by postmortem examination. The disease pattern and the special course of the ACC are described.

Adult↗

Glucose transport during cell cycle in IM9 lymphocytes.

Hexose uptake of the transformed lymphocyte cell line IM9 was analysed with respect to kinetics, responsiveness to insulin and insulin-like growth factor I and to cell cycle dependency. We found a Km of 0.76 mM and a Vmax of 14.9 nMol/min/mg protein for 2-deoxy-D-[3H]glucose uptake. This Km is in accordance with the values described for the erythrocyte type and the brain type glucose transporter. Hexose uptake of IM9 lymphocytes was not altered by physiological concentrations of insulin or IGF I. We investigated the 2-deoxy-D-[3H]glucose transport in cells, enriched in the different cell cycle phases by counterflow elutriation. The results were calculated for hypothetical pure fractions. Hexose uptake per cell is more than doubled during the S-phase and returns in G2-cells to the basal value of G1-phase.

Cell Cycle↗

Large-scale cell separation by centrifugal elutriation.

Countercurrent elutriation is a powerful method for fast and gentle large-scale isolation of cells according to size and density. Current limitations of this approach are the suboptimal selectivity that is obtained and the fact that the total number of cells that can be separated per run is restricted. We describe a new separation chamber, which was calculated according to the hydrodynamic boundaries of the counterflow separation. In comparison to the chamber commonly in use, a fivefold higher cell number can be separated with this chamber at an increased separation selectivity. Furthermore the use of this chamber, which fits to the standard Beckman equipment, avoids large sampling volumes.

Cell Line↗

[Severe combined immune defect. Presentation of exfoliative dermatitis with eosinophilia and lymphadenopathy].

BACKGROUND: We report on 9 infants with severe combined immunodeficiency (SCID), who additionally showed signs of Omenn syndrome with an exfoliative dermatopathy, alopecia, enlarged lymph nodes, a hepatomegalia and a striking blood eosinophilia. The immunological evaluation revealed the characteristic abnormalities of SCID with cellular and humoral immunodeficiency. All patients however had the unusual finding of mature T cells in the peripheral blood. By HLA typing these cells were noted to be of maternal origin in 5 patients. In the other 4 patients the T cells were of host origin. We asked for additional differences between both patient groups. METHOD: Both patient groups were analyzed and compared with regard to case histories, clinical, laboratory and histopathological parameters. RESULTS: No clinical or laboratory differences could be detected. The histomorphologic analysis of patients with or without maternal T cells was identical. The skin biopsies showed dense cell infiltrations of lymphocytes, histiocytes and eosinophils, in the enlarged lymph nodes the latter two cell types predominated. Therefore the only difference between the 2 patient groups was the presence or absence of maternal T cells. CONCLUSION: Since the Omenn syndrome is found in association with maternal as well as patient derived T cells, we postulate that the peculiar symptoms of this syndrome are the result of a T cell induced inflammatory reaction, similar but not identical to a graft versus host reaction, occurring on the basis of an inborn SCID.

Bone Marrow↗

[Expert assessment of asbestos-induced lung damage].

Asbestos is a mineral of special technical properties and therefore used in many products all over the world. The inhalation of asbestos causes chronic inflammation of lung--the asbestosis--and pleura--pleuraplaques and pleuritis--and is responsible for mesothelioma and lung cancer. Under normal conditions the diagnosis asbestosis is easy because of the typical x-ray findings and the history of intensive exposure of asbestos. In rare conditions the history of exposure is uncertain and the diagnosis might be difficult. The expected anuity depends on the loss of lung-function. First we find a restrictive ventilatory disorder i.e. a reduction in VC and compliance. Later after progress of the disease the gasexchange is impaired. In case of mesothelioma or lungcancer the person is generally expected to be unable to work.

Asbestosis↗

Serum immunoreactive erythropoietin of children in health and disease.

Serum immunoreactive erythropoietin (siEPO) was determined in cord serum from neonates (n = 97, gestational age 36-43 weeks), in healthy children from birth to adolescence (n = 260) and in children with haematological (n = 30), renal (n = 10) and congenital heart diseases (n = 70). In healthy children siEPO levels decreased after birth (geometric mean cord siEPO 35.6 mU/ml with 95% range of 17-56 mU/ml in eutrophic, nondistressed fetuses) and reached lowest values during the first 2 months (geometric mean siEPO 11.5 mU/ml). Thereafter siEPO levels increased slightly and were constant between 2 months and adolescence. The geometric mean siEPO for healthy children after birth was 18.8 mU/ml with 95% range of 7-47 mU/ml. These estimates were not significantly different from normal adult values. In newborns with fetal distress (n = 15) cord siEPO was significantly elevated (geometric mean 63.0 mU/ml; P less than 0.001). In children with haematological disease, siEPO and Hb concentration were inversely correlated (log siEPO (mU/ml) = 4.1-0.20 x Hb (g/dl); r = -0.62; P less than 0.0005). This relationship was significantly different in children with chronic renal failure (log siEPO (mU/ml) = 0.67 + 0.035 x Hb (g/dl); r = 0.50; P = 0.1). In children with heart disease the geometric mean siEPO was 19.2 mU/ml with 95% range 8-65 mU/ml for cyanotic (SaO2 less than 94%) and 17.7 mU/ml with 95% range of 12-36 mU/ml for acyanotic patients. In this group siEPO values were inversely correlated to the arterial oxygen content (log siEPO (mU/ml) = 1.61-2.04 x oxygen content (l/l); r = -0.28; P less than 0.02).

Adolescent↗

Expression of p53 in human leukemic cell lines.

The cell-encoded p53 antigen seems to be tightly associated with various human malignancies. We have analyzed biochemical properties of p53 in two different cell lines derived from patients with ALL or ANLL. p53 was found in elevated levels in both leukemic cell lines compared to unstimulated or stimulated normal lymphocytes. High levels of p53 in these cell lines are due to an extended stability of p53 protein rather than to different rates of synthesis. p53 from both cell lines formed low- and high-molecular weight oligomers which revealed that p53 exists in a heterogenous population in these tumor cells. The presence of immunologically different subsets of p53 was demonstrated by sequential immunoprecipitation experiments with different p53 specific monoclonal antibodies. Our results showed structural and immunological variabilities of p53 in cell lines derived from human tumors and may thus provide an insight into the role p53 may play in human malignancies.

Burkitt Lymphoma↗

[Short- and long-term results of tuberculosis therapy with a fixed combination of isoniazide, prothionamide and diaminodiphenylsulfone combined with rifampicin].

This is a report on 912 patients treated during 1973 to 1979 for pulmonary tuberculosis and/or extrapulmonary organ involvement. These patients had been treated with a fixed tablet combination of isoniacide, prothionamide and diaphenyl sulfone in association with rifampicin and partly other substances. It was the aim of our study to examine this form of therapy in respect of side effects and effectivity. 535 of these 912 patients were followed up for as long as 13 years (maximum follow-up period). According to the criteria of the American Tuberculosis and Respiratory Diseases Association the patients were suffering from 182 cases of pulmonary tuberculosis of only slight extension, 490 of moderate extension and 130 of large extension, as well as 55 cases of pleuritis, 67 extrapulmonary organ tuberculoses and 1 tuberculosis of the bronchial mucosa. Allergic skin reactions occurred in 0.7% of the cases, and in 0.9% there were neurological disturbances such as vertigo, paroxysms and polyneuropathies. In 7.4% of the patients there was an increase in serum enzyme activities of SGOT, SGPT, Y-GT as a sign of hepatotoxicity. In 5.5% of the patients there were several gastrointestinal concomitant phenomena such as sensation of fullness, nausea, and vomiting. Under IPD therapy the hemoglobin valuedropped on the average by 12% up to the 5th or 6th week of treatment and rose subsequently to almost normal levels. No permanent damage was seen in any of the patients under observation. In the moderately extended tuberculosis cases disinfection occurred on the average between the 6th and 8th week of treatment, in the greatly extended cases on the average in the 9th to 13th week.(ABSTRACT TRUNCATED AT 250 WORDS)

Dapsone↗

Role of insulin during cell cycle in a myeloid cell line.

The characteristics of insulin receptor binding and structure and its proliferative and metabolic action in a human leukemic cell line was investigated during the cell cycle. Exponentially growing cells were separated by counterflow centrifugation which fractionates cells primarily on the basis of size into subpopulations representing G0/G1, S, and G2 + M cells. This method avoids disturbance of the cellular metabolism. After separation the cells showed a viability of at least 92%, underwent further proliferation, and remained morphologically unchanged, which was shown by electron microscopy. The cells could be enriched to 70-90% purity for G0/G1 phase and 50-60% purity for S and G2 + M phase, respectively, which was shown by DNA flow-cytometry. Specific binding of insulin could be demonstrated in G0/G1, S, and G2 + M enriched cells. Insulin binding sites decreased from 20-25,000 per cell in G0/G1 to 1-2,000 in S and increased to 30-50,000 in G2 + M. The affinity of insulin binding remained nearly constant during the cell cycle. The specificity of the insulin receptor could also be demonstrated by covalent crosslinking of the receptor to radiolabeled ligand in all enriched cell fractions. Glucose transport was stimulated by insulin independently of cell cycle. An increase to 140% of control was observed at an insulin concentration of 10 ng/ml. In contrast, glycogen synthesis could only be stimulated by insulin in the G0/G1 phase. An increase to 140% of control was already reached at 0.25 ng/ml insulin. Insulin in concentrations of 1 and 10 ng/ml stimulated the transit to S-phase in cycling, but not in resting, cells. The growth promoting action of insulin could be investigated by consecutive DNA analysis of the separated cells which had been stimulated by insulin.

Cell Cycle↗

Three other types of duodenal polyps: mucosal cysts, focal foveolar hyperplasia, and hyperplastic polyp originating from islands of gastric mucosa.

Seven cases are reported that initially presented on endoscopic examination as duodenal polyps originating from islands of gastric mucosa within the duodenal bulb. Microscopic examination revealed mucosal cysts (MC), focal foveolar hyperplasia (FFH), and hyperplastic polyp (HPP). These lesions must be added to the list of neoplastic and tumorlike lesions of the duodenum that may endoscopically present as polyps.

Aged↗

[The rhythm of melatonin synthesis in the epiphysis and its control by light].

The paper deals with the central regulation of the circadian rhythm of the melatonin in the pineal gland by light according to the literature. Examples of the effects of melatonin and their inclusion in the total endocrine complexity are pointed out. Possibilities for a therapy of chronobiological diseases with bright light resulting from animal experiments are discussed in connection with requirements for a future application to the therapy of human beings.

Circadian Rhythm↗