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Biomedical subjects

D Hartmann

Publications and source records attributed to D Hartmann.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1990

Pharmacokinetic modelling of the plasma concentration-time profile of the vitamin retinyl palmitate following intramuscular administration.

Seven healthy male volunteers (21-24 y) received by the ventro-gluteal route a single dose of 100,000 I.U. of the vitamin retinyl palmitate (RP) in a water-miscible preparation (W) and 5 weeks later the same dose in an oily solution (S). After administration of W median (range) peak plasma concentrations of 5.6 (4.4-8.7). 10(3) micrograms l-1 were reached after 12 h and high levels persisted for another 50 h. At 144 h levels were still, by a factor 3, higher than baseline. Plasma levels of RP after S remained close to baseline (20-50 micrograms.l-1) suggesting negligibly low bioavailability. The plasma level profile of RP after W could well be described by use of a one-compartment model with Weibull-type absorption and Michaelis-Menten elimination. The median (range) absolute bio-availability (estimates of lower limits) was 42 (32-52) per cent.

Adult↗
PubMed1990

Establishment and characterization of somatic hybrids between human differentiated macrophages and mouse myeloma NS1 cells.

Human macrophages obtained from circulating monocytes matured in vitro by culture for seven days in hydrophobic flexible teflon bags were successfully fused with murine myeloma NS1 cells. Six of 20 clones, selected for their adherence properties, were further studied. All possessed human chromosomes (mean number ranging from 4 to 14 depending on the clones studied), exhibited non-specific esterases (but no peroxidase activity) and expressed CD14 antigen and C3 receptors (but no MAX-1 antigen). Moreover, the hybridomas retained phagocytic activity and high interferon plus lipopolysaccharide-activable cytolytic activity against tumor cells.

Animals↗
PubMed1990

Lack of effect of tenoxicam on dynamic responses to concurrent oral doses of glucose and glibenclamide.

1. In a single-blind, placebo controlled study the influence of tenoxicam on responses of glucose, insulin and C-peptide to oral doses of glucose and glibenclamide was examined in 16 healthy male volunteers. 2. The subjects received once daily doses of 2.5 mg glibenclamide for 12 days. From day 5 through 12 eight subjects received concomitantly 20 mg tenoxicam once daily and the remaining eight subjects received placebo. 3. On days 1, 4, 5 and 12 glibenclamide was taken with 75 g glucose and blood glucose, serum insulin and C-peptide were measured over 5 h. Plasma levels of glibenclamide and tenoxicam (where appropriate) were followed over 10 h. 4. Characteristic parameters of blood glucose and insulin and C-peptide responses did not change significantly with time (day) and there was no difference between both treatment groups. 5. Baseline insulin increased from 11.7 mu l-1 on day 1 to 15.6 mu l-1 on day 4 (P = 0.009), likewise baseline C-peptide increased from 478 pmol l-1 to 530 pmol l-1 (P = 0.05), but there was no further change in the subsequent treatment period. 6. The AUC of the glibenclamide plasma concentration-time curve did not show changes with time or differences between treatment groups. The mean (s.d.) oral clearance of tenoxicam was 2.5 (1.5) ml min-1 and appeared slightly higher than in previous studies. 7. It was concluded that tenoxicam did not affect overall glycoregulation in healthy subjects under glibenclamide steady state conditions.

Adult↗
PubMed1989

[Retinoids in the prevention and treatment of cancer].

There is experimental evidence that vitamin A-deficiency plays a role in tumorigenesis. Therefore, vitamin A was used in the treatment of malignant tumors. Unfortunately, it was found that the compound was too toxic and therefore its clinical usefulness was limited. Chemical modifications of the vitamin A molecule lead to what is now called the retinoids, which in general show higher efficacy and better tolerance than vitamin A itself. In this article some of the retinoids like 13-retinoic acid (Roaccutan) and etretinate (Tigason) are described with regard to their antitumor activity in animals and man. In widespread malignant disease the efficacy so far is limited to patients with basal cell carcinoma and mycosis fungoides. However, in the treatment of premalignant or in the prevention of recurrent disease retinoids have found much broader application. This is demonstrated by the successful treatment of several diseases like oral leukoplakia, actinic keratosis, xeroderma pigmentosum, bronchial metaplasia and superficial bladder carcinoma.

Animals↗
PubMed1989

Investigation of seal mycoplasmas for their cytotoxic potential on tracheal organ cultures of SPF and gnotobiotic rats.

Eleven mycoplasma strains isolated from several organs of diseased seals during the seal epidemic in the Baltic and North Sea in 1988 and the seal epidemic along the New England coast in 1979-1980, were investigated for their cytotoxic potential by inoculation into tracheal organ cultures of SPF and gnotobiotic rats. The mycoplasma strains belonged to three different species. Administration of 2.0 x 10(2) to 4.5 x 10(7) colony forming units of all of the mycoplasma strains caused an inhibition of the ciliary activity and cytopathological changes within the epithelial cells appearing as bleb-like protuberances by observation with the inverted microscope. There was, however, a distinct difference in the strength of the cytopathological changes caused by the three mycoplasma species. Semi- and ultrathin sections of tracheal rings infected with the seal mycoplasma strain 852, observed by light and electron microscopy, revealed a heavy tissue injury of the tracheal epithelium and dumbbell-shaped mycoplasmas adhering to degenerated epithelial cells.

Animals↗
PubMed1989

Lack of effect of acitretin on the hypothrombinemic action of phenprocoumon in healthy volunteers.

A possible influence of the aromatic retinoid acitretin on the hypothrombinemic action of phenprocoumon was investigated in 10 healthy male volunteers, 22-33 years of age. In a run-in period of 17 days the prothrombin complex activity (Quick) of the subjects was adjusted by individual doses of phenprocoumon (range 1.5-3 mg/day) to a therapeutic level of around 20% (INR = 3.6). Afterwards the dosage regimens were kept unchanged until day 40 when 60 mg oral vitamin K1 were administered. From day 18 to day 28 once daily doses of 50 mg acitretin were applied concurrently with phenprocoumon. The mean (+/- SD) prothrombin complex activity increased slightly and steadily from 19 +/- 1% on day 10 over 22 +/- 1% on day 18 to 24 +/- 4% on day 28 and reached 27 +/- 4% on day 38 (the corresponding INRs were 3.30, 2.91, 2.71 and 2.46 respectively). There were, however, no relevant changes of the Quick values in any subject which could be attributed to acitretin. It can be concluded that, under the present experimental conditions, acitretin did not affect significantly the anticoagulant action of phenprocoumon.

4-Hydroxycoumarins↗
PubMed1989

[Unusual course of malignant synovioma of the flexor tendon sheath of the hand].

The authors report a synovial sarcoma of the hand with an unusual case history and a favorable outcome after two years. A forty-four-year old woman suffering from uncharacteristic pain in the right hand with slightly abnormal EMG-findings for the median nerve was treated by operative release of the carpal tunnel. No unusual findings were discovered intraoperatively. The patient continued suffering from disabling pain for another year so that a second operation was performed by another surgeon. He discovered a tumor behind the median nerve which could not be removed radically because of profuse bleeding. In spite of diagnosing a sarcoma, the patient refused further surgery, however combined radio- and chemotherapy was administered for one year. The tumor was reduced in size but did not disappear. Following open biopsy and proved presence of sarcoma, the remaining tumor was removed by amputating the ulnar part of the hand. Two years following this last operation, the patient is free of local symptoms and there is no evidence of metastases.

Adult↗
PubMed1989

The pharmacology of reversible monoamine oxidase inhibitors.

The older monoamine oxidase inhibitors (MAOIs) are mechanism-based, irreversible inhibitors of MAO; most inhibit both the A and B forms of MAO. Several of the drugs are hydrazine derivatives which have non-specific effects other than MAO inhibition. These properties convey disadvantages, which may be seen as serious, though infrequent, adverse events--the 'cheese effect', hepatotoxicity, amphetamine-like activity, orthostatic hypotension and anticholinergic effects. New, reversible MAOIs stem from a variety of chemical classes and are more specific in their effects, with relatively rapid onset of action, direct relationship between plasma concentration and pharmacological effect, and no prolonged carry-over phenomena.

Administration, Oral↗
PubMed1988

Interleukin-1 alpha modulates collagen gene expression in cultured synovial cells.

The effects of porcine interleukin-1 (IL-1) alpha on collagen production were studied in cultured human rheumatoid synovial cells. Addition of 0.05-5 ng of IL-1/ml into the cultures resulted in a dose-dependent decreased rate of collagen released into the medium over 24 h. To determine whether this inhibition was due to secondary action of prostaglandin E2 (PGE2) secreted in response to IL-1, cultures were incubated in presence of various inhibitors of arachidonate metabolism. Depending on the cell strains, these inhibitors were able to suppress or diminish the effect of IL-1, suggesting that PGE2 is involved in the mechanism. Depression of collagen production caused by IL-1 mainly affected type I collagen and therefore led to a change in the type I/type III collagen ratio in the extracellular medium. Steady-state levels of mRNA for types I and III procollagens were estimated by dot-blot hybridization and compared with the amounts of respective collagens produced in the same cultures. IL-1 generally increased procollagen type I mRNA, but to a variable extent, as did indomethacin (Indo). Depending on the cell strain, the combination of indo and IL-1 could elevate the mRNA level of type I procollagen compared with Indo alone. These results did not correlate with the production rate of collagen in the medium, which was diminished by exposure to IL-1. The level of mRNA for collagen type III was not greatly changed by incubation with IL-1, and a better correlation was generally observed with the amount of type III collagen found in the medium. These data suggest that an additional control mechanism at translational or post-translational level must exist, counterbalancing the stimulatory effect of IL-1 on collagen mRNA transcription. It is likely that IL-1 could modulate the production of collagen in synovial cells by an interplay of different mechanisms, some of them limiting the effect of primary elevation of the steady-state mRNA level.

Bucladesine↗