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Biomedical subjects

D Hartmann

Publications and source records attributed to D Hartmann.

At least 19 recordsLinked to original sources
PubMed1992

Development of astroglial cells in the proliferative matrices, the granule cell layer, and the hippocampal fissure of the hamster dentate gyrus.

The histogenesis of the hamster dentate gyrus was studied with light and electron microscopy and antisera against the astrocyte-associated antigens vimentin and GFAP, in order to follow the differentiation of radial glial cells and astrocytes. The formation of the stratum granulosum is preceded by the establishment of successive dentate matrices, which are formed by cells that leave the ventricular neuroepithelium and occupy positions above the fimbria (suprafimbrial), below the pial surface (subpial), and within the dentate hilus (hilar dentate matrix). The subpial dentate matrix invades the marginal zone of that region of the cerebral wall, where the stratum granulosum will later develop. From the beginning of its existence on embryonal day 13 (E13) up to its disappearance about postnatal day 7 (P7), it is characterized by a high content of GFAP-positive cells and mitoses. This indicates early gliogenesis in the dentate anlage, long before the appearance of the stratum granulosum. Many of the bipolar GFAP-positive cells are oriented parallel to the pial surface and have focal contacts to the pial basement membrane. The establishment of the subpial dentate matrix splits the primordial radial glial scaffold of the hippocampal/dentate anlage into two bundles: 1) the suprafimbrial bundle that retains its original radial position between ventricle and pial surface; and 2) the dorsal glial bundle that traverses the ventral tip of the pyramidal cell layer of future CA3. The latter is pushed dorsolaterally, away from the pial surface, by the enlargement of the subpial dentate matrix and, later, by the suprapyramidal blade. The latter emerges around birth as small radial columns of granule cells located between the bent basal parts of the ventralmost fibers of the dorsal glial bundle and the subpial dentate matrix. From the beginning of its existence it is traversed by unipolar "secondary" radial glial fibers that appear to originate from the subpial dentate matrix. Both the supra- and the infrapyramidal blades seem to elongate by the addition of postmitotic granule cells and "secondary" radial glial cells from the subpial dentate matrix to the growing end of the primordial stratum granulosum. The hilar dentate matrix that is localized in the prospective hilar region, inside the growing stratum granulosum, also contains glial cells that seem to be incorporated into the stratum granulosum. The dentate gyrus is demarcated from the CA1 region of the hippocampus proper by GFAP-positive cells that populate the hippocampal fissure, and that also originate from the subpial dentate matrix.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Destruction of meningeal cells over the medial cerebral hemisphere of newborn hamsters prevents the formation of the infrapyramidal blade of the dentate gyrus.

Meningeal cells participate in the development of the cerebellum both by stabilizing the extracellular matrix of the pial surface and by organizing the radial glial scaffold and the lamination of the cerebellar cortex. In the present study we investigated possible influences of meningeal cells on the development of the dentate gyrus, whose ontogenesis has many similarities to that of the cerebellum. Meningeal cells were selectively destroyed by injecting newborn hamsters with 25 micrograms 6-hydroxydopamine (6-OHDA) into the interhemispheric fissure. Twenty-four hours postinjection (p.i.) the meningeal cells over the medial cerebral hemispheres were completely destroyed. Thirty days p.i. the infrapyramidal blade of the dentate gyrus was almost completely missing, while the suprapyramidal blade was hypertrophied, extending with its medial tip almost up to the medial surface of the cortex. In order to ascertain that this maldevelopment was caused by the destruction of meningeal cells, another group of hamsters was pretreated with normetanephrine (NMN) which inhibits the extraneuronal uptake of 6-OHDA into meningeal cells. In this group the meningeal cells were unaffected by the treatment, and the morphology of the dentate gyrus was normal 30 days p.i. of 6-OHDA plus NMN. When the meningeal cells were destroyed in later stages of development (postnatal days 1-5), alterations of the dentate gyrus could be induced only up to the fourth postnatal day; thereafter, 6-OHDA treatment left it unchanged. This indicates a critical period of meningeal cell influence that coincides with the period of existence of the subpial dentate matrix. Analysis of the time course of the defective development revealed that in the first 5 days p.i. 1) meningeal cells over the medial cerebral hemisphere were destroyed and removed, 2) the pial basement membrane over both the dentate anlage and the diencephalon thinned and ruptured, and the adjacent brain parts fused focally, 3) many cells of the subpial dentate matrix disappeared from their subsurface position, 4) the number of "immature" cells increased in the hilus and the subgranular zone of the suprapyramidal blade, 5) the suprapyramidal blade elongated and thickened considerably, while the infrapyramidal blade did not form. Beyond 5 days p.i. those parts of the pial surface of the dentate anlage that had not fused with the diencephalon were repopulated with meningeal cells. This reappearance of meningeal cells was accompanied by 1) the restitution of the normal morphology of the basement membrane, 2) the reappearance of neuronal and glial cells below the pial surface, and 3) the formation of fragments of the infrapyramidal blade which later developed a normal appearing lamination.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Effect of acitretin on the response to an intravenous glucose tolerance test in healthy volunteers.

The effect of the synthetic retinoid acitretin (A) on the disposition of blood glucose and on the serum insulin response following the IV infusion of 139 mmol glucose over 10 min (IGTT) has been investigated in six healthy subjects. The IGTT was performed on Days 1, 10 and 24. On Days 3 to 10 A 50 mg/d was administered. Several parameters of glucose disposition and insulin response (K-values, AUC) were assessed. As a methodological variant, the profiles over time of blood glucose and serum insulin were evaluated by model calculations using the 'minimal model'. Acitretin did not influence any parameter of glucose disposition. The area under the insulin-time curve (baseline corrected) was significantly decreased from 1.20 mU.min.l-1 on Day 1 to 0.89 mU.min.l-1 on Day 10, and was 0.91 mU.min.l-1 on Day 24. The model-derived 'insulin sensitivity' increased from 13.10(-4) l.mU-1.min-1 on Day 1 to 20.10(-4) l.mU-1.min-1 on Day 10 and was 18.10(-4) l.mU-1.min-1 on Day 24. The results suggest that A increased sensitivity to endogenous insulin. It supports a recent report showing greater insulin sensitivity in patients treated with the synthetic retinoid etretinate.

Acitretin↗
PubMed1992

Effect of tumor burden and route of administration on the immunotherapeutic properties of polyinosinic-polycytidylic acid stabilized with poly-L-lysine in carboxymethyl cellulose [Poly(I,C)-LC].

We examined the immunomodulatory and therapeutic activities of poly(I,C)-LC. Mice received a subcutaneous (s.c.) injection of sufficient numbers of MBL-2 lymphoma cells to produce in 1 week either a high or low tumor burden. A week after tumor cell injection, poly(I,C)-LC treatment was initiated; the agent was administered intraperitoneally (i.p.) at 5 mg/kg twice a week or at 2.5 or 0.5 mg/kg every day or as an intravenous (i.v.) injection at 0.5, 0.05, or 0.005 mg/kg three times a week. Poly(I,C)-LC treatment significantly increased antitumor effector cell functions in a variety of organs (including spleen, lungs, and peritoneum), as shown by increased killing of MBL-2 cells in vitro and increased tumor cell killing by natural killer cells and macrophages. Furthermore, prolongation of survival correlated with peritoneal macrophage tumoricidal activity when poly(I,C)-LC was given i.p. and with pulmonary effector cell function (including natural killer, cytolytic T-lymphocyte and macrophage tumoricidal activity) when the agent was administered i.v.

Animals↗
PubMed1992

Human interferons-alpha inhibit the production of immunoglobulin M by secreting and nonsecreting lymphoblastoid cell lines.

It is well known that human lymphoblastoid interferon-alpha [HuIFN-alpha(ly)] may either increase or decrease antibody production by B cells, in vivo as well as in vitro, depending on the experimental conditions and the system used. We compare here the effect of HuIFN-alpha(ly) and human recombinant interferon-alpha (rHuIFN-alpha) on immunoglobulin M (IgM) production by secreting and nonsecreting human B-like lymphoblastoid cells, respectively, ST8246, and Daudi cells. Under our experimental conditions, Daudi cells were less sensitive to the antiproliferative effect of IFN than previously reported by other authors, and ST8246 cells were insensitive to this antiproliferative effect. In contrast, IgM production was profoundly affected in both cell lines. Thus, we could discriminate between the effect on cell growth from the effect on the immune response. Using high-pressure liquid chromatography (HPLC) separation, mu chains and monomeric and pentameric IgM were distinguished from cytosolic and membrane-associated fractions and from culture medium (extracellular IgM). Pentameric extracellular IgM and monomeric membrane IgM were diminished by HuIFN-alpha(ly) treatment, respectively, in ST8246 cells and in Daudi cells. We conclude that HuIFN-alpha(ly) induces regression of B-like lymphoblastoid cells toward a less mature phenotype.

Antibody-Producing Cells↗
PubMed1992

Initial studies in humans with the novel gastrointestinal lipase inhibitor Ro 18-0647 (tetrahydrolipstatin).

Excessive intake of dietary fat contributes to the development and maintenance of both obesity and hyperlipidemia. Inhibition of gastrointestinal lipases could decrease the amount of ingested fat that is absorbed systemically by preventing the hydrolysis of triglycerides. Ro 18-0647, a chemically synthesized derivative of the natural product lipstatin, inhibits the action of gastrointestinal lipases. Initial studies in humans have shown that Ro 18-0647 can reliably increase fecal fat excretion. Ro 18-0647 has also been shown to be well tolerated in the majority of normal volunteers and obese patients studied. Further research must be conducted to determine whether clinical endpoints of weight loss or cholesterol lowering can be produced by using this new pharmacologic principle.

Dietary Fats↗
PubMed1992

Host-donor interactions in healing of human split-thickness skin grafts onto nude mice: in situ hybridization, immunohistochemical, and histochemical studies.

The behavior of host and donor cell lines in human split-thickness skin grafts onto nude mice was studied by in situ hybridization (ISH) using genomic DNAs as probes, and immunohistochemically with species-specific or cross-species specific antibodies, at different stages ranging from day 3 to more than 1 year following grafting. Changes in the graft vascular and interstitial extracellular matrix were also assessed using species-specific or cross-species specific antibodies to human or murine type I, III, and IV collagens. Finally, transplant reinnervation was investigated using antibodies to various nerve cytoplasmic antigens and the thiocholine method to demonstrate acetylcholinesterase. Using these methods we were able to show the following: (1) the graft epidermis that is not replaced by mouse keratinocytes is progressively colonized by recipient Langerhans cells (LCs); (2) revascularization of the grafts begins soon by inoculation of the graft vessels with the host microcirculatory bed, and mouse endothelial cells growing into preexisting human capillary tubes produce a new basement membrane, prior to the replacement of the original one; (3) within 3-5 days following grafting, mouse fibroblasts migrate into the graft dermis. The density of the human and murine fibroblast populations then progressively increases. Characterization of the interstitial collagens identifies both human and murine type I and III collagens. Production of type III collagens decreases during the progression of fibrogenesis while human type I collagen becomes the predominant matrix protein; (4) transplant reinnervation is deficient, and neurites growing into severed graft nerve trunks were never detected.

Animals↗
PubMed1992

Effects of dentin proteins, transforming growth factor beta 1 (TGF beta 1) and bone morphogenetic protein 2 (BMP2) on the differentiation of odontoblast in vitro.

We have studied the effects of dentin proteins, of Transforming Growth Factor beta 1 (TGF beta 1) and Bone Morphogenetic Protein (BMP2) on the differentiation of odontoblasts in vitro. The total EDTA-soluble fraction of dentin proteins, prepared from rabbit incisors was further separated by chromatography on DEAE-Cellulose and heparin-agarose columns. While the total EDTA-soluble fraction of dentin had no effect on cultured dental papillae, fractions retained on both columns were able to initiate functional differentiation of preodontoblasts of isolated day-17 first lower mouse molar dental papillae cultured in vitro. TGF beta 1 and BMP2, both stimulated the matrix secretion by dental papillae cells. TGF beta 1 and BMP2, combined with the inactive total EDTA-soluble fraction, stimulated odontoblast differentiation. An active fraction retained on DEAE-Cellulose completely lost the inductive activity after incubation with a neutralizing anti-TGF beta antibody. These results demonstrate that a TGF beta-like molecule present in dentin could interact with some component which acts as a modulator of its activity on the initiation of the cytological and functional differentiation of odontoblasts.

Animals↗
PubMed1991

Spatial arrangement of coenzyme and substrates bound to L-3-hydroxyacyl-CoA dehydrogenase as studied by spin-labeled analogues of NAD+ and CoA.

The synthesis of nitroxide spin-labeled derivatives of S-acetoacetyl-CoA, S-acetoacetylpantetheine, and S-acetoacetylcysteamine is described. These compounds are active substrates of L-3-hydroxyacyl-CoA dehydrogenase [(S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase, EC 1.1.1.35] exhibiting vmax values from 20% to 70% of S-acetoacetyl-CoA itself. S-Acetoacetylpantetheine and S-acetoacetylcysteamine form binary complexes with the enzyme and exhibit ESR spectra typical for immobilized nitroxides. In the case of spin-labeled pantetheine, the radical is more mobile. When spin-labeled substrates are bound simultaneously to each active site of this dimeric enzyme, spin-spin interactions differentiate between two alternate orientations of the substrate [Birktoft, J.J., Holden, H.M., Hamlin, R., Xuong, N.H., & Banaszak, L.J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8262-8266]. The fatty acid moiety is thought to be located in a cleft between two domains whereas a large part of the CoA moiety probably extends into the solution. NAD+, spin-labeled at N6 of the adenine ring, is an active coenzyme of L-3-hydroxyacyl-CoA dehydrogenase (60% vmax). Complexes with the enzyme exhibit ESR spectra typical of highly immobilized nitroxides. Binding of coenzyme NAD+ causes conformational changes of the binary enzyme/substrate complex as revealed by changes in the ESR spectrum of spin-labeled S-acetoacetylpantetheine.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1991

Pharmacokinetics of digoxin and main metabolites/derivatives in healthy humans.

Three healthy, young male volunteers received doses of 0.6 and 1.2 mg of specifically labelled [3H]digoxin each by intravenous (i.v.) bolus injection and oral (p.o.) administration in accordance with a randomized four-way crossover design. Plasma, urine, and feces samples were taken over an interval of 144 h after drug administration. Total radioactivity and individual radioactivity assignable to digoxin and its metabolites were measured. After i.v. administration, the mean +/- SD recovery of total radioactivity, as percent of dose, was complete, urine 81.3 +/- 2.0% and feces 17.1 +/- 2.8%. The mean recovery of digoxin and that of its metabolites in urine was digoxin 75.6 +/- 3.0%, dihydrodigoxin 2.8 +/- 1.6%, digoxigenin bisdigitoxoside 1.6 +/- 0.1%, and additional metabolites 1.5 +/- 0.3%. Judging from the metabolite data in urine and considering the 5% impurity of the administered dose, metabolism of digoxin appeared to be insignificant after i.v. administration. The total and renal clearances of digoxin were, on average, 193 +/- 25 ml min-1 and 152 +/- 24 ml min-1. The mean steady state volume of distribution was 489 +/- 73 L and the mean residence time 41 +/- 5 h. For the metabolites dihydrodigoxin and digoxigenin bisdigitoxoside the mean residence times were on average 35 +/- 9 h and 53 +/- 11 h; the renal clearances were 79 +/- 13 ml min-1 and 100 +/- 26 ml min-1. After p.o. administration, the mean recovery of total radioactivity, as percent of the dose, was also complete, urine 65.7 +/- 1.98% and feces 31.6 +/- 7.6%. The mean recovery of digoxin and that of its metabolites, as percent of dose, in urine was digoxin 51.5 +/- 11.4%, dihydrodigoxin 4.5 +/- 3.9%, digoxigenin bisdigitoxoside 1.9 +/- 0.1%, polar metabolites 5.5 +/- 3.8%, and additional metabolites 1.3 +/- 0.6%. After p.o., as compared to i.v. administration, larger amounts of all the metabolites were formed in accordance with first pass metabolism/degradation. Maximum mean plasma concentrations of 4.3 +/- 2.5 ng ml-1 and 9.5 +/- 1.1 ng ml-1 for digoxin were observed at 40 +/- 10 min after p.o. administration of 0.6 and 1.2 mg of the drug. The mean absolute bioavailability of digoxin from an aqueous solution was 0.67 +/- 0.14. Renal clearance and mean oral residence time for digoxin were on average 176 +/- 28 ml min-1 and 37 +/- 4 h after p.o. administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1991

[Serum hyaluronic acid and phospholipase A2 in an arthritic population].

Serum hyaluronic acid (HA) and A2 phospholipase (A2PL) activity were measured by radioimmunoassay (Pharmacia) and using a specific phospholipid substrate respectively, as potential markers of osteoarthritic synovitis. With neither age, treatment nor sample time taken into consideration, the concentration of HA (micrograms/ml) was 585 +/- 1,054 in rheumatoid arthritis, 379 +/- 409 in knee osteoarthrosis, 272 +/- 384 in hip osteoarthrosis, 131 +/- 144 in low back pain and 44 +/- 23 in osteoporosis, with no significant difference between the groups. HA was nevertheless found to be significantly higher in knee osteoarthrosis patients than in normal controls, when samples were drawn at the same time of day. Physical exercise (pedalling), as well as 20 hours lying flat and an intra-articular injection of corticosteroids did not cause any significant variation in serum HA levels in knee osteoarthrosis patients, in contrast to 20 hours of rest in the controls. A2PL activity was significantly higher in osteoarthrosis patients than in the controls, decreased with rest and corticosteroids and was not dependent upon sample time.

Aged↗
PubMed1991

Study of an inhibitor of plasminogen activator (tranexamic acid) in the treatment of experimental osteoarthritis.

The effects of tranexamic acid, an inhibitor of plasminogen activator, were evaluated in a rabbit model of osteoarthritis induced by section of the knee joint anterior cruciate ligament. Prophylactic treatment administered intramuscularly thrice weekly for 12 or 24 weeks significantly reduced cartilage destructive lesions, increased cartilage hypertrophy but did not prevent changes in cartilage water and proteoglycan content. A suppression of synovial membrane stromelysin and collagenase activity was found while phospholipase A2 activity was unaffected.

Animals↗
PubMed1979

Pathological cell aggregates in bone marrow cultures from patients with various hematological diseases.

Non-clonal growth of macroscopic cell aggregates in methylcellulose cultures of abnormal marrow is described. They were seen in all patients with Graft-versus-Host Disease, graft rejection, and autoimmune disease presumably directed against hemopoietic cells, we found them in 35% of patients with primary hematological neoplasias and rarely in patients with solid tumors. They were never encountered in 80 healthy controls. The aggregates originated from small cell clumps which sedimented with the "buffy coat" in contrast to normal bone marrow particles. They contained tumor cells, grafted myeloid cells, or target cells of autoimmune disease in association with a widely varying amount of macrophages. Preliminary results suggest that the frequency of macrophages within the aggregates correlates inversely with the aggressiveness of the clinical condition. We propose that appearance of such aggregates in an indicator of immune activation; we expect that further quantitation of the phenomenon will reveal important clinical correlations and provide a model for the study of host defense to "foreign" cells.

Anemia, Hemolytic, Autoimmune↗
PubMed1979

[Immune profile in patients with Hodgkin's disease in long-term remission after cytostatic chemotherapy].

13 patients in complete and prolonged remission after treatment with cytostatic chemotherapy for disseminated Hodgkin's disease have been investigated for immune competence by a total of 27 immunological parameters. 11 patients had abnormal values for lymphocyte populations, lymphocyte function and skin tests. The immune profile described is suitable for long-term evaluation of patients under immunosuppressive therapy.

Adolescent↗
PubMed1979

Vindesine. A clinical trial with special reference to neurological side effects.

A good tumoricidal activity of vindesine (VDS) has been reported in a variety of animal tumors and in human leukemias and lymphomas. We treated 22 patients who had received no prior chemotherapy and were suffering from a variety of malignant neoplasms with 0.5 mg/m2 to 3.0 mg/m2 VDS i. v. once or three times at weekly intervals and recorded the clinical, hematologic, and especially, neurological side effects. Clinically we observed fatigue in nine patients, paresthesias in seven, myalgias in three, vertigo and diarrhea in two, and skin pains, tinnitus, gastric pains, alopecia, and tremor in one patient each. There was no obvious dose-action relationship. Paravenous injection caused cellulitis similar to that seen with vincristine. No side effects were apparent in liver (SGPT) and renal (creatinine) function tests. Hematologically there was a clear trend toward leukopenia with higher doses of DVA and a mean increase in the thrombocyte count by 51 X 10(3)/mm3 was found (sign test: P greater than 0.05). The hemoglobin level did not change. Clinical neurological examination and monitoring by electroneurography revealed no changes in tensiometer performance, motor and sensory nerve conduction velocity, motor or sensory nerve action potential amplitudes, or H-reflex responses. There was dose-related diminution of the proprioceptive reflexes, especially in the lower extremities. Even with as little as 2.0 mg/m2 VDS i. v. at weekly intervals for 3 weeks Achilles and patellar tendon reflexes were diminished or absent in all patients.

Action Potentials↗
PubMed1979

Steady-state turnover and body pool of ascorbic acid in man.

The time course of radioactivity in plasma and urine after oral administration of a single dose of (1-14C)ascorbic acid has been followed in healthy nonsmoking male volunteers. The investigation was carried out under steady state conditions with regard to ascorbic acid intake (30 to 180 mg/day). Using pharmacokinetic principles, turnover, pool size, and rates of metabolism and excretion could be calculated. It was found that the half-life of ascorbic acid was inversely related to the dosage and that the pool could be increased to about 20 mg/kg bodyweight by increasing the dosage. It was concluded that on a daily intake of about 100 mg ascorbic acid this pool size would be reached in 95% of the population.

Adult↗