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D Damm

Publications and source records attributed to D Damm.

At least 37 records · Page 2Linked to original sources
PubMed1994

Heparin-binding EGF-like growth factor gene is induced in the mouse uterus temporally by the blastocyst solely at the site of its apposition: a possible ligand for interaction with blastocyst EGF-receptor in implantation.

Heparin-binding EGF-like growth factor (HB-EGF) is a newly discovered member of the EGF family of growth factors. HB-EGF can bind to two loci on cell surfaces, heparan sulphate proteoglycans and EGF-receptor (EGF-R), and either one or both of these interactions could play a role in cell-cell interactions. In the rodent, increased endometrial vascular permeability at the site of blastocyst apposition is considered to be an earliest discernible prerequisite event in the process of implantation and this event coincides with the initial attachment reaction between the blastocyst trophectoderm and uterine luminal epithelium. This investigation demonstrates that the HB-EGF gene is expressed in the mouse uterine luminal epithelium surrounding the blastocyst 6-7 hours before the attachment reaction that occurs at 2200-2300 hours on day 4 of pregnancy. It was further demonstrated that this gene is not expressed in the luminal epithelium at the site of the blastocyst apposition during the progesterone-maintained delayed implantation, but is readily induced in the luminal epithelium surrounding an activated blastocyst after termination of the delay by an estrogen injection. In vitro studies showed that HB-EGF induced blastocyst EGF-R autophosphorylation, and promoted blastocyst growth, zona-hatching and trophoblast outgrowth. These results suggest possible interactions between the uterine HB-EGF and blastocyst EGF-R very early in the process of implantation, earlier than any other embryo-uterine interactions defined to date at the molecular level.

Animals↗
PubMed1994

Interference in clinical laboratory tests, with special regard to the bilirubin assay: effects of a metabolite of the new prolyl 4-hydroxylase inhibitor, Lufironil.

During the toxicological examination of the fibrosuppressive agent, Lufironil (INN), in rats a dose-dependent positive reaction for urinary bilirubin was observed. This positive reaction was found in quantitative assays, and when using test strips. The positive reaction for bilirubin in these assay systems was caused by a metabolite of Lufironil. It was not due to drug toxicity, and it was not caused by any endogenous substrate produced under the influence of Lufironil. The compound responsible for this reaction was isolated by HPLC and its structure determined by spectroscopic methods. The structure was confirmed by synthesis, starting from pyridine-2,4-dicarboxylate. The synthesized compound and the compound in urine gave an identical reaction with the test reagent for bilirubin.

Administration, Oral↗
PubMed1994

Concentrations of adipsin in blood and rates of adipsin secretion by adipose tissue in humans with normal, elevated and diminished adipose tissue mass.

Adipsin, which is identical to complement factor D, is synthesized by fat cells, circulates in the bloodstream and is profoundly deficient in mice with genetic and hypothalamic obesity. With the recent cloning of human adipsin, a quantitative human immunoassay has been developed. In the present study, we measured adipsin blood concentrations in humans with increased and decreased adipose stores as well as adipsin secretion by adipose tissue obtained from lean and obese individuals. The results demonstrate that adipsin is released by human adipose tissue fragments as has previously been shown in mice, and that, in contrast to obese mice, blood adipsin concentrations were not reduced in the obese humans tested in this study. We also observed that blood adipsin concentrations can vary as a function of feeding or adiposity, in that they tend to be mildly elevated in obese individuals or mildly reduced in individuals with total lipo-atrophy, cachexia related to AIDS and anorexia nervosa. Thus, the circulating concentration of adipsin tends to correlate positively with degree of adiposity. Clearly, no deficiency in blood adipsin concentrations or adipsin secretion by adipose tissue was observed in the obese individuals studied.

Adipose Tissue↗
PubMed1993

Heparin-binding epidermal growth factor-like growth factor expression in cultured fetal human vascular smooth muscle cells. Induction of mRNA levels and secretion of active mitogen.

Heparin-binding EGF-like growth factor (HB-EGF) is a recently identified potent mitogen for smooth muscle cells (SMC). To explore whether SMC can also synthesize HB-EGF, cultured fetal human vascular SMC (FHVSMC) were analyzed for the production of HB-EGF mRNA and active growth factor. It was found that in FHVSMC, HB-EGF has the characteristics of an early response gene in that (i) the addition of fresh 10% fetal calf serum to serum-starved FHVSMC led to a rapid and transient rise in HB-EGF mRNA levels with a maximal induction of 12-14-fold occurring within 2-4 h, (ii) the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) also elevated HB-EGF mRNA levels rapidly and transiently with a maximal induction of 7-8-fold occurring at 2-4 h, and (iii) cyclohexamide at 40 micrograms/ml markedly increased basal, serum-, and TPA-induced HB-EGF mRNA levels. In addition, HB-EGF mRNA levels were increased 7-11-fold by addition of either HB-EGF itself, platelet-derived growth factor, or basic fibroblast growth factor, all potent SMC mitogens. Besides synthesizing HB-EGF mRNA, FHVSMC were found to release into conditioned medium a bioactive HB-EGF-like protein that cross-reacted with anti-HB-EGF antibody.

Cell Division↗
PubMed1993

Heparin-binding EGF-like growth factor: characterization of rat and mouse cDNA clones, protein domain conservation across species, and transcript expression in tissues.

Clones were obtained that encode the rat and mouse forms of heparin-binding EGF-like growth factor (HB-EGF), a potent mitogen for smooth muscle cells, fibroblasts and keratinocytes that is proposed to be derived from a transmembrane precursor. Within the HB-EGF precursor sequences predicted from these cDNAs, the region corresponding to the secreted ("mature") factor was found to represent one of the least well conserved areas when compared to human or monkey HB-EGF (73-76% sequence identity). Regions of high sequence conservation included the proposed juxtamembrane and transmembrane domains, as well as a proposed heparin-binding region within the "mature" factor. Northern blotting experiments using the HB-EGF clones as probes revealed HB-EGF transcript expression in multiple tissues, particularly lung, skeletal muscle, brain, and heart.

Amino Acid Sequence↗
PubMed1993

Cell-specific posttranslational processing of the surfactant-associated protein SP-B.

Pulmonary surfactant-associated protein B (SP-B) is a 9-kDa lung-specific protein expressed in alveolar epithelial type II cells and Clara cells. The protein markedly increases the surface activity of phospholipids and is an active component in some surfactants in clinical use. SP-B is produced from a 43-kDa precursor protein by proteolytic cleavage of flanking regions from both the NH2- and COOH-terminal ends of the active protein. In this study we have compared the nature of the posttranslational processing of the SP-B precursor in type II cells and in a heterologous cell line transfected with the SP-B precursor. We found that isolated type II cells produce the 9-kDa form of SP-B from the precursor through a series of intermediates detectable in the cell lysates. In contrast Chinese hamster ovary cells stably transfected with the full-length human SP-B precursor produce the precursor and a 26-kDa intermediate but not the 9-kDa protein. The precursor protein in both cell types is glycosylated with NH2-linked sugars. Our results suggest there is cell specificity in the posttranslational processing of the SP-B precursor.

Animals↗
PubMed1993

Concentrations of cefodizime in bronchial secretions after single intravenous administration.

UNLABELLED: The concentrations of cefodizime (HR 221, CAS 69739-16-8) in bronchial secretions were measured after administration of a single intravenous bolus of 2 g in 19 patients requiring fibreoptic bronchoscopy for diagnostic purposes or as therapeutic follow-up. These concentrations, which were obtained in absence of inflammation of the mucosa, were compared to serum concentrations obtained simultaneously. The penetration into bronchial secretions was rapid, maximum levels of between 1 and 5 mg/kg being already observed 1 h after injection. Most concentrations remained about 1 mg/kg throughout the whole observation period of about 5.5 h. The percent penetration amounted to about 1.5% of the corresponding serum concentrations. CONCLUSION: Concentrations well above the MIC90s of the relevant respiratory pathogens--S. pneumoniae, M. catarrhalis, H. influenzae, K. pneumoniae--and Enterobacteriaceae were reached in bronchial secretions after intravenous injection of a single 2 g dose of cefodizime. Even higher levels may be expected in the usual condition of inflamed bronchial mucosa as found in respiratory infections.

Adult↗
PubMed1992

Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue.

A cDNA for human adipsin was isolated and shown to encode a protein sharing 98% amino acid sequence similarity with the protein sequence previously determined for purified natural human complement factor D. Like mouse adipsin, recombinant human adipsin displays the enzymatic activity of human complement factor D, cleaving complement factor B only when B is complexed with activated complement component C3. We conclude that human adipsin is equivalent to complement factor D and that adipsin is the homologue of factor D in rodents. Adipose tissue is a major site of synthesis of human adipsin/complement factor D mRNA, but unlike the case in rodents, human adipsin mRNA is also expressed in monocytes/macrophages. The data presented here, demonstrating the equivalence of human adipsin to complement factor D and its high level of expression in fat, suggest a previously unsuspected role for adipose tissue in immune system biology.

Adipose Tissue↗
PubMed1990

Plasma concentrations of methadone during postoperative patient-controlled extradural analgesia.

Plasma concentrations of methadone were measured by gas chromatography in 16 patients receiving extradural methadone by continuous infusion for relief of postoperative pain. Venous blood samples were taken after a loading dose of extradural methadone 2 mg and during infusion of 0.46 mg h-1 plus patient-controlled increments of 0.2-1 mg. Mean (SD) plasma concentration of methadone was 9.8 (2.1) ng ml-1 at 15 min; this did not change significantly during the first 2 h, after which it increased gradually to 32.2 (4.6) ng ml-1 (P less than 0.001) at the end of 24 h. The mean quantity of extradural methadone required to produce effective analgesia was 10.3 (1.8) mg during the first 12 h after operation and 6 (1.0) mg for the subsequent 12 h. The mean amount of methadone for effective analgesia on the second day was 7.6 (1.1) mg. No adverse effects were detected during the 2-3 days of methadone therapy. Plasma concentration of methadone increased significantly during patient-controlled infusion of extradural methadone in the first 24 h after operation, suggesting rapid vascular uptake. Systemic activity of the drug contributes to the analgesic effect of extradural methadone.

Adult↗
PubMed1990

Pharmacokinetics of cefodizime during continuous ambulatory peritoneal dialysis.

In a single-dose open cross-over trial we studied the pharmacokinetics of cefodizime 1 g in four uraemic patients treated by continuous ambulatory peritoneal dialysis (CAPD). Cefodizime was administered, successively with a wash out, (a) iv over 3 min and (b) by intraperitoneal (ip) administration together with the dialysate fluid (2 litres). Concentrations of cefodizime were measured by HPLC in blood and dialysate samples collected during an 8-h dwell period and in additional dialysate samples collected up to 48 h after drug administration. The mean (relative) total clearances following the iv and ip administration were 23 and 31 ml/min, respectively, and the terminal half-lives 5.5 and 6.7 h, respectively. Following iv administration, the peritoneal clearance was approximately 0.5 ml/min. After ip administration high concentrations of cefodizime were measured in the dialysate throughout the dwell period and systemic availability was good (80%) but variable.

Adult↗
PubMed1990

Cytokine modulation of keratinocyte cytokines.

There is increasing evidence that epidermal cytokines may have an important role in mediating inflammatory and immune responses in the skin. A number of cell types in the epidermis are capable of secreting cytokines including keratinocytes, Langerhans cells, melanocytic cells, and even Merkle cells. Keratinocytes are the major source of cytokines in the epidermis and have been reported to secrete IL-1, IL-3, IL-6, IL-8, CSF, TNF alpha, TGF alpha, TGF beta, and PDGF. Normally these cytokines are not actively secreted by keratinocytes; however, a number of agents are capable of mediating keratinocyte cytokine production, including cytokines themselves. We examined the effect of a number of cytokines on keratinocyte IL-1, IL-6, GM-CSF, and PDGF production. It was found that these keratinocyte cytokines are all modulated by one or more cytokines, including several that keratinocytes themselves secrete. These effects appear to be mediated by high-affinity cytokine receptors on keratinocytes. We are only beginning to understand the molecular mechanisms underlying the production, regulation, and precise role of keratinocyte cytokines in normal and diseased skin; however, recent studies suggest that cytokines secreted by epidermal cells and lymphoid cells may be important modulators of keratinocyte cytokine production.

Animals↗
PubMed1989

Adipsin and complement factor D activity: an immune-related defect in obesity.

Adipsin is a serine protease that is secreted by adipocytes into the bloodstream; it is deficient in several animal models of obesity, representing a striking example of defective gene expression in this disorder. Recombinant mouse adipsin was purified and its biochemical and enzymatic properties were studied in order to elucidate the function of this protein. Activated adipsin has little or no proteolytic activity toward most substrates but has the same activity as human complement factor D, cleaving complement factor B when it is complexed with activated complement component C3. Like authentic factor D, adipsin can activate the alternative pathway of complement, resulting in red blood cell lysis. Decreased (58 to 80 percent) complement factor D activity, relative to lean controls, was observed as a common feature of several experimental models of obesity, including the ob/ob, db/db, and monosodium glutamate (MSG)-injected mouse and the fa/fa rat. These results suggest that adipsin and the alternative pathway of complement may play an unexpected but important role in the regulation of systemic energy balance in vivo.

Adipose Tissue↗
PubMed1989

IFN-beta 2, B cell differentiation factor 2, or hybridoma growth factor (IL-6) is expressed and released by human epidermal cells and epidermoid carcinoma cell lines.

IL-6, which is also known as IFN-beta 2, hybridoma growth factor, hepatocyte-stimulating factor, and B cell differentiation factor, mediates acute phase responses including fever, has lymphocyte-stimulating capacities, and antiviral activity. IL-6 is produced by monocytes, fibroblasts, certain lymphocytes, and various tumor cells. The present study demonstrates that this multifunctional cytokine is released also by normal human epidermal cells (EC) and human epidermoid carcinoma cell lines (A431, KB). Accordingly, supernatants derived from freshly isolated EC, long term keratinocyte cultures, A431, or KB cells stimulated the proliferation of a hybridoma growth factor/IL-6-dependent plasmacytoma cell line (B9). IL-6 constitutively was produced in the presence of serum proteins. The addition of IL-1 alpha, IL-1 beta, or the tumor promoter PMA significantly enhanced the synthesis and release of EC-derived IL-6 (EC-IL 6). Like monocyte or fibroblast-derived IL-6, EC-IL-6 exhibited Mr microheterogeneity within 21 and 28 kDa. Similarly in Western blotting experiments an antiserum directed against human rIFN-beta 2/IL-6 detected the different Mr forms of EC-IL-6. Moreover, this antiserum was able to block the B9 cell growth-promoting capacity of EC-IL-6 strongly suggesting that this EC-derived mediator is closely related, if not identical with IL-6. This was further confirmed by Northern blot analysis detecting IL-6 specific mRNA both in long term cultured keratinocytes and A431 cells by hybridization with a cDNA fragment encoding for B cell differentiating factor 2/IL-6. Therefore, in addition to the production of other cytokines as previously reported, EC and in particular keratinocytes also synthesize and release IL-6. This further supports the important regulatory role of the epidermis during the pathogenesis of inflammatory, autoimmune, and neoplastic diseases.

Animals↗
PubMed1989

Simultaneous determination of the main metabolites of dipyrone by high-pressure liquid chromatography.

A simple, rapid, and sensitive procedure is described for the determination of the main metabolites of dipyrone in plasma and urine. After adding isopropyl aminoantipyrine as internal standard and a deproteinizer the plasma of urine samples are alkalized and extracted with chloroform. The residue of the evaporated organic phase is dissolved in mobile phase and separated by HPLC. The compounds are detected by ultraviolet light at 265 nm. The following metabolites can be determined selectively by this method: 4-methylamino-antipyrine, 4-aminoantipyrine, 4-formylaminoantipyrine and 4-acetylaminoantipyrine. The detection limit for all four metabolites is 0.1 microgram/ml in plasma and 2 micrograms/ml in urine. The results of a human pharmacokinetic study are also presented.

Aminopyrine↗
PubMed1987

Nucleotide and amino acid sequences of pulmonary surfactant protein SP 18 and evidence for cooperation between SP 18 and SP 28-36 in surfactant lipid adsorption.

Pulmonary surfactant is a lipid-rich material that promotes alveolar stability by lowering the surface tension at the air-fluid interface in the peripheral air spaces. The turnover of surfactant phospholipids in the alveolar space is fast, and several lines of evidence suggest there is rapid formation and replenishment of the phospholipid surface film during normal respiration. Specific proteins may regulate these dynamic surface properties. The predominant surfactant protein is a well-characterized, lipid-associated glycoprotein, SP 28-36 (28-36 kDa). A second group of very hydrophobic proteins has recently been shown to affect the surface activity of surfactant phospholipids. We have isolated this group of hydrophobic proteins, herein called SP 5-18 (5-18 kDa), from canine surfactant and have shown by NH2-terminal sequence analysis that at least two proteins, SP 5-8 and SP 18, are present in this group. We have derived the full amino acid sequence of SP 18 from the nucleotide sequence of the cDNAs identified with oligonucleotide probes that were based on the NH2-terminal amino acids of SP 18. The protein isolated from extracellular surfactant appears to be a fragment of a much larger precursor protein (40 kDa). The amino acid sequence of SP 18 is markedly hydrophobic and contains two possible bilayer-spanning domains. We have shown that SP 18 and the glycoprotein SP 28-36 have a cooperative, calcium-dependent action in promoting the formation of phospholipid surface films.

Amino Acid Sequence↗
PubMed1987

Application of a new method for measurement of plasma methadone levels to the use of epidural methadone for relief of postoperative pain.

A method is described for measurement of plasma methadone concentrations using a gas chromatic technique that is rapid and specific and enables the detection of concentrations of less than 1 ng/ml in plasma samples of only 1 ml. The method, when used to determine the plasma methadone levels in patients given continuous epidural infusions of methadone plus on-demand supplementation for relief of postoperative pain, showed plasma methadone plateaus of around 10 ng/ml (starting at 15 min and lasting over 2 hr) and 20 ng/ml (starting at 3 hr and lasting over the period of treatment) (P less than 0.001) after an initial 2-mg methadone epidural bolus and with continuous epidural methadone. Mean plasma methadone levels of around 10 ng/ml were associated with pain relief. Analgesia could be safely maintained for 24 hr.

Adult↗
PubMed1985

Structure of canine pulmonary surfactant apoprotein: cDNA and complete amino acid sequence.

The apoproteins of pulmonary surfactant (PSAP) are thought to be critical for normal surfactant function. They bind to surfactant phospholipids and enhance their ability to form surface films in vitro. These acidic glycoproteins have monomeric molecular weights of 36,000, 32,000, and 28,000 (PSAP-36, -32, and -28). Each member of this family of proteins has a similar amino acid composition and their differences in electrophoretic mobility are due in part to glycosylation. We have derived the full amino acid sequence of PSAP-32 from the nucleotide sequence of PSAP cDNA. A cDNA library was prepared from canine lung poly(A)+ RNA and screened with oligonucleotide probes that were based on the NH2-terminal amino acids of PSAP-32 determined by Edman degradation. This protein has the striking feature of collagen-like and non-collagen-like sequences in the same polypeptide chain. There are 24 Gly-Xaa-Yaa triplets, where Yaa is often hydroxyproline. These repeats comprise one-third of PSAP near the NH2 terminus. The remaining two-thirds of PSAP is resistant to bacterial collagenase digestion and contains a possible N-glycosylation site near the carboxyl terminus. The NH2-terminal one-third of PSAP-32 probably contains the cysteine involved in interchain disulfide bonds.

Amino Acid Sequence↗