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Biomedical subjects

R Burkhardt

Publications and source records attributed to R Burkhardt.

At least 19 recordsLinked to original sources
PubMed1991

The systemic influence of recombinant interleukin 2 on the manifestations of lepromatous leprosy.

14 patients with lepromatous leprosy received twice daily injections of 10 micrograms recombinant interleukin 2 (rIL-2), by the intradermal route, in the skin of the back for 8 d (total dose, 160 micrograms). Lymphokine administration was accomplished without drug toxicity, or the development of acute nerve damage. The majority of patients developed nontender axillary lymphadenopathy during the course of treatment. Local injection sites showed progressively larger zones of induration, peaking at 24 h and persisting for many days. Early 12-h reactions were of a macular, erythematous nature and exhibited an increasingly striking diurnal variation. The morning injection sites were three- to fourfold larger in diameter than those placed in the evening (9 am to 9 pm). Systemic manifestations of intradermal rIL-2 administration were noted. Peripheral blood T cells, including CD4+ and CD8+ phenotypes, increased 2-2.5-fold and NK cells increased sixfold. Elevations in [3H]TdR incorporation into peripheral blood mononuclear cells occurred to a variety of mycobacterial antigens, but not to those of Mycobacterium leprae. Within 2 wk, biopsies at sites far removed from the back showed increased infiltration of mononuclear cells in 12 of 14 patients. Immunocytochemistry revealed the presence of newly emigrated CD4+ T cells, monocytes, and dermal CD1+ Langerhans cells. Endothelial cells of small dermal vessels expressed major histocompatibility complex class II determinants on their surface. Transmission electron microscopy of these specimens revealed markedly enlarged endothelial cells with many surface projections extending into the lumen as well as extravasating lymphoid cells. The numbers of acid-fast M. leprae in the peripheral sites were examined by slit smear and in biopsies of matched leprosy lesions taken before and after IL-2 administration. Within 2 mo, slit smears showed a 0.5 log or greater reduction in 12 of 14 patients, with a mean for all patients tested of 0.5 log units. Biopsy specimens showed a 1 log unit or greater reduction in the bacterial index (B.I.) in 6 of 14 patients. Historical controls in this Nepalese population showed a 0.5 log unit reduction after multidrug therapy over a period of 12 mo. Thus, after 8 d of IL-2 injections, a fivefold reduction in B.I. was observed during the first 2 mo of the study. Antibody levels against M. leprae phenolic glycolipid 1 (PGL-1) and lipoarabinomanan B were markedly elevated after IL-2 injections, while PGL-1 antigen levels were reduced. We conclude that the administration of rIL-2 has had a significant effect in decreasing the total body burden of M. leprae.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Chronic myeloproliferative disorders: prognostic importance of new working classification.

Variants of chronic myeloproliferative disorders (CMPD) were compared according to their clinical features and classified by bone marrow biopsy appearances. Subsequently, this classification was further evaluated using survival data and histological variables from iliac crest biopsy specimens of an additional 1391 patients, making a total of 2241 patients available for analysis of outcome. The patients were grouped again into three main classes: "typical"; "variant"; and "transformed". "Typical" comprised the "classic" groups. "Variant" included the less uniform myeloproliferative syndromes, distinguished also by more variable clinical features, a different prognosis, and a greater tendency to fibrotic and blastic transformation. "Transformed" defined the end stages of both "typical" and "variant" types. Ten subgroups were distinguished by different histology and prognosis. Particular prognostic importance was assigned to atypia and immaturity of haemopoiesis, predominance of individual haemopoietic cell line, number and anomalies of megakaryocytes and progressive fibrosis. It is suggested that the proposed subclassification would be helpful for studies of epidemiology and therapeutic trials by allowing more homogeneous groups to be recognised.

Bone Marrow↗
PubMed1989

[The morphology of coxsackie B virus infections of the nervous system].

Neuropathological studies were conducted into 20 virologically secured Coxsackie-B virus infections of infants and adults, with the nervous system being involved. Inflammatory processes affect both gray and white cerebral regions as well as the peripheral nervous system, and in adulthood they may take the form of severe necrotising encephalitis. Necroses of that kind may be recordable from various regions of the central nervous system. Notwithstanding tempestuous progress in the development of monoclonal antibody kits, culturing of Coxsackie viruses will continue to be of substantive importance to diagnosis, because of the small size of pathogens.

Adolescent↗
PubMed1988

Fatty acids stimulate phosphatidylcholine synthesis and CTP:choline-phosphate cytidylyltransferase in type II pneumocytes isolated from adult rat lung.

The regulation by cyclic AMP and fatty acids of phosphatidylcholine (PC) synthesis in rat alveolar type II cells was studied. In contrast with results with hepatocytes, cyclic AMP and its potent chlorophenylthio analogue had no inhibitory effect on [Me-14C]choline incorporation into PC in pulse-chase studies with alveolar type II cells. The inclusion of the fatty acids palmitate, oleate or linoleate in the chase incubation medium stimulated the incorporation of [Me-14C]choline into PC by type II cells. The effect of palmitate, which was more pronounced than that of the other fatty acids, appeared to be concentration-dependent. Increased [Me-14C]choline incorporation into PC was paralleled by an accelerated disappearance of the radiolabel from choline phosphate, which is consistent with an activation of CTP:choline-phosphate cytidylyltransferase. This enzyme is considered to be rate-limiting in the synthesis of PC de novo by type II cells. As fatty acids are also substrate for PC synthesis, their effect could also be due to compensation for a fatty acid deficiency. To test this possibility, fatty acid synthesis in the type II cells was stimulated by addition of lactate. Even then, an additional stimulation of PC synthesis by palmitate was observed, which supports the regulatory influence of exogenous fatty acids. Incubation of type II cells in the presence of 0.2 mM-palmitate resulted in a 45% increase in the membrane-bound CTP:choline-phosphate cytidylyltransferase activity, whereas the soluble activity remained unchanged. Choline kinase activity in the soluble fraction increased by 48%. However, the increase in choline kinase is unlikely to be responsible for the increased metabolic flux through the choline phosphate pathway, because there is a relatively large pool of choline phosphate in type II cells. Therefore it is suggested that the microsomal CTP:choline-phosphate cytidylyltransferase is the form of this enzyme which is active in surfactant PC synthesis, and possibly has a regulatory role in this pathway.

Animals↗
PubMed1988

Comparative histology of malignant lymphomas in lymph node and bone marrow.

Lymph node and bone marrow biopsies of 226 patients with malignant lymphomas were available for evaluation and comparison. 120 of the 226 lymphoma patients had classifiable infiltration in both lymph node and bone marrow and these were used for comparison. Congruence in the histologic subtypes in lymph node and bone marrow was found in 91 patients (76%). The majority of the 29 cases with divergent histologies showed ML of low grade malignancy in the bone marrow even with long time intervals between the two biopsies. The most notable in this group were seven cases who had ML centroblastic/centrocytic in the lymph node biopsy and ML immunocytic in the bone marrow, although none had a serum M-component. 65 of the 106 patients excluded from comparison had involvement in only one organ, the others had unclassifiable or equivocal histologies in either lymph node or bone marrow or in both. The findings are discussed with respect to the histologic behaviour of the lymphomas. The results show that comparison between lymph node and bone marrow findings in patients with ML is feasible and clinically relevant.

Bone Marrow↗
PubMed1988

Bone marrow in megakaryocytic disorders.

Megakaryocytic disorders induce serious consequences: myelofibrosis and osteomyelosclerosis, hemorrhage, and thrombosis. They are characterized by four main structural types: myeloproliferation, dysmegakaryocytosis, amegakaryocytosis, and secondary megakaryocytosis. Whereas the first and third are primarily defined by histology, the second and fourth are to be interpreted only in the context of clinical findings. Nevertheless, bone marrow biopsy has revealed marked quantitative and qualitative anomalies of megakaryocytes also in these groups: isolation, pleomorphism, and degeneration of nuclei, and immaturity, vacuolization, and disruption of cytoplasm. The pathophysiologic impact of these impressive changes is almost unknown. It deserves further consideration.

Bone Marrow↗
PubMed1987

[Diagnosis and prognosis of hairy cell leukemia].

During 1966 and 1986 202 patients with hairy cell leukemia in the bone marrow biopsy were observed. All hairy cells were categorized according to their nuclear morphology into ovoid subtype, convoluted subtype and indented subtype. The overall survival of 113 non-splenectomised patients was 11 months. However, the median survival time of each subtype differed considerably with 55 months for the ovoid subtype, 8 months for the convoluted and 6 months for the indented type. The prognosis of splenectomy patients were significantly better at a p-value of less than 0.0001 than the survival of the non-splenectomised patients. The median survival time was 59 months. Also in this group of patients the prognosis was different for the ovoid, convoluted and indented subtype. The median survival time of the ovoid subtype is not yet reached, despite a observation time of more than 180 months. In contrast, the survival time for the convoluted and indented subtypes was 26 months. These data elucidate that at least part of the heterogeneity in the clinical course of this disease can be explained by the morphologically distinct subtypes and that splenectomy prolongs profoundly but to a different degree the survival of patients with all three histological subtypes. The response rate to r.-IFN alpha-2b is higher in patients with the ovoid than with the convoluted and indented subtypes.

Adult↗
PubMed1987

Nucleotide sequence of the fhuC and fhuD genes involved in iron (III) hydroxamate transport: domains in FhuC homologous to ATP-binding proteins.

The transport of Fe3+ into cells of Escherichia coli occurs via siderophores and the uptake through the outer membrane of three Fe3+-siderophore compounds containing hydroxamate residues requires three specific receptor proteins. In contrast, transport through the cytoplasmic membrane is catalysed by three common proteins encoded by the fhuB, fhuC and fhuD genes. The nucleotide sequence of a DNA fragment containing the fhuC and fhuD genes has been determined: the open reading frame of fhuC contains 795 nucleotides which encode a polypeptide with a molecular weight of 29,255 and the largest open reading frame of the fhuD region comprises 888 nucleotides. However, we propose that translation of fhuD initiates at the fourth potential start codon resulting in a polypeptide with a molecular weight of 28,282. Both proteins are moderately nonpolar and membrane-bound. They lack obvious signal sequences. Segments of the FhuC protein display strong homology to ATP-binding proteins, suggesting a function in Fe3+ uptake similar to the ATP-binding proteins of transport systems that depend on periplasmic proteins. This study completes the nucleotide sequence of the fhu operon which consists of the four genes fhuA fhuC fhuD fhuB arranged in this order on the E. coli chromosome and transcribed from fhuA to fhuB.

Amino Acid Sequence↗
PubMed1987

Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study.

Retrospective histologic analyses of bone biopsies and of post mortem samples from normal persons of different age groups, and of bone biopsies of age- and sex-matched groups of patients with primary osteoporosis and aplastic anemia show characteristic age dependent as well as pathologic changes including atrophy of osseous trabeculae and of hematopoiesis, and changes in the sinusoidal and arterial capillary compartments. These results indicate the possible role of a microvascular defect in the pathogenesis of osteoporosis and aplastic anemia.

Adolescent↗
PubMed1986

Working classification of chronic myeloproliferative disorders based on histological, haematological, and clinical findings.

Bone marrow biopsies of 850 patients with chronic myeloproliferative disorders were taken at initial diagnosis; and 169 sequential biopsies over periods of one to 188 months. Three micron sections of all biopsies were evaluated semiquantitatively with reference to the proliferating cell lines, anomalies of megakaryocytes, and fibrosis or osteosclerosis. Correlations between initial histological findings, clinical, haematological, and survival data were analysed statistically. The predominant cell lines distinguished the classical entities of polycythaemia vera, primary thrombocythaemia, and chronic myeloid leukaemia and correlated with their different prognoses, while megakaryocytes characterised subgroups that were prone to fibrotic or blastic transformation. Based on the initial histological, clinical, and haematological data analysed a working classification of chronic myeloproliferative disorders was proposed that permits recognition of both typical and atypical cases of chronic myeloproliferative disorders.

Adolescent↗
PubMed1985

Quantitative monitoring of fundus changes.

The proposed method allows to discover and quantify small changes in series of fundus photographs which are normally not directly comparable. The principle of geometric conformality of small parts between the fundus and its photographs is developed into a practical method of stereoscopic measurement, numerical adjustment and quantitative evaluation. Very high accuracy is possible without special conditions on repeated fundus photography. The aim is to create a theoretical and methodical basis for ophthalmoscopic change detection with image-processing computers.

Fundus Oculi↗
PubMed1984

Chronic myeloproliferative disorders (CMPD).

The wide clinical range of CMPD can be understood as leukaemia of pluripotent stem cells according to the pathogenic concepts reviewed above. Blastic metamorphoses of CMPD are regressions to a more primitive level of cellular differentiation. The predominant proliferative cell line characterizes the classical entities of PV, PT and CML, and their different prognoses. Pure erythrocytic and megakaryocytic proliferations are more compatible with sustained physiologic bone marrow functions than granulocytic proliferations. The combinations of granulocytic and megakaryocytic growth are especially prone to develop MF/OMS, in which participation of immune reactions, of granulocytic and of platelet factors is probable. An etiologic role for ineffective thrombocytopoiesis is supported by experimental as well as by histologic evidence. Myelofibrosis and osteomyelosclerosis may have similar causes, but develop independently. The prevalence of the female sex among thrombocythaemic patients was proven statistically also for the increase of giant type megakaryocytes in the form of clusters in the bone marrow, and for longer median survival of females in CMPD, especially when there is megakaryocytosis in the bone marrow. It is assumed that females may be better protected against the detrimentous effects of abnormal platelet production. An arbitrary classification according to haematologic and histologic criteria was applied to PV, PT and CML, and groups with typical and atypical haematologic and histologic signs were distinguished. The latter cannot be separated from each other by their various haematologic manifestations, but by histology and their different propensity to progress into more immature and/or fibrotic stages. Three major groups are characterized by histology: mixed granulocytic-megakaryocytic myelosis with giant megakaryocytic clusters, a similar variant with diffuse distribution of giant megakaryocytes, and immature and/or pleomorphic megakaryocytic myelosis. Transitions from each of these groups have been observed as well as transitions from each of the typical CMPD-entities into these less typical forms. CML, frequently accompanied by dwarf-megakaryocytes, often develops into pleomorphic megakaryocytic or blastic myelosis. Blastic dedifferentiation and myelofibrosis manifest themselves as closely related end stages, to which principally all groups proceed after a longer or shorter period of time, modified by the proliferating cell lines in each group. Clinical, experimental and histologic evidence of this natural history has been reviewed, with special emphasis on the re-evaluation of technically optimal bone marrow biopsies of untreated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Lymphoproliferations in the bone marrow: identification and evolution, classification and staging.

Bone marrow biopsies from 3229 patients with lymphoproliferative disorders and 1156 patients with benign or reactive lymphoproliferations were investigated and criteria for distinguishing between them are given. Bone marrow involvement was found in 89% of multiple myeloma, 64% of non-Hodgkin's lymphomas and 8% of Hodgkin's disease. According to the predominant proliferative cell type there were five major entities in multiple myeloma and non-Hodgkin's lymphomas: (1) plasmacytic; (2) lymphocytic; (3) hairy cell; (4) immunocytic; (5) centrocytic. These were further classified into distinct subtypes each of which had independent prognostic significance. The mode of spread of the lymphoproliferative disorders in the bone marrow showed one of six architectural patterns, which together with the quantity of infiltration in the biopsy (reflecting the tumour cell burden) had significant predictive value. These results demonstrate the value of bone marrow biopsies in the identification, classification and staging of lymphoproliferative disorders, as well as in monitoring the course of disease and the response to therapy.

Bone Marrow↗