Biomedical subjects

D Damm

Publications and source records attributed to D Damm.

At least 19 recordsLinked to original sources

PubMed2001

Reassessment of ADHD in a historical cohort of children treated with stimulants in the period 1969-1989.

The operational diagnostic criteria for ADHD or HKD were not at hand in Denmark before 1994, when WHO's International Classification of Diseases -10 (ICD-10) was introduced. The criteria for ADHD/HKD were well known at our clinic, but when treating children with stimulants the criteria used clinically prior to 1994 were less specific than today. The aims of this paper are to examine the prevalence of ADHD in a historical cohort of children treated with stimulants during the period 1969-1989 and to reassess a wide range of comorbid disorders and sociodemographic characteristics in order to compare aspects of the given treatment with the modern recommendations. At our clinic 208 children (183 boys) were given stimulants during the period 1969-1989. Case records on these probands were reassessed retrospectively for DSM-IV criteria regarding ADHD and comorbid disorders as well as for characteristics of stimulant treatment. Sixty-five percent met full criteria for an ADHD diagnosis. Including Subthreshold ADHD as many as 81 % of the cohort were re-diagnosed with ADHD. Prevalence rates of conduct problems and anxiety disorder were similar to previous prospective ADHD studies. The use of stimulants during the period 1969-1989 were in accord with modern guidelines. This cohort is comparable to other clinically based ADHD cohorts as regards inattentive, hyperactive/impulsive symptoms, comorbidity, impairment, gender differences, intelligence and socio-economic status (SES).

Adolescent↗

PubMed2001

Gilles de la Tourette syndrome in a child with congenital deafness.

We present the case of a 10-year-old boy, Sam, with congenital deafness and Gilles de la Tourette Syndrome (GTS). GTS is characterised by multiple motor tics and one or more vocal tics that wax and wane. Due to his deafness Sam never developed vocal language but instead used sign language from the age of four. His tic disorder rapidly accelerated from the age of seven over a six-month period and soon sign language was incorporated into tics as complex "vocal" tics. Bursting out "words" in sign language would also occur in front of people unfamiliar with sign language and often with an obscene content although this was not evident to someone not trained in sign language. To our knowledge this is the first reported case of a congenital deaf child with GTS. The case presented here supports previously published work that the intentional share of the tics in GTS is very small. This case also questions former theories on which regions and circuits of the brain are involved in GTS.

Anti-Dyskinesia Agents↗

PubMed2000

Altered patterns of gene expression in response to myocardial infarction.

The use of cDNA microarrays has made it possible to simultaneously analyze gene expression for thousands of genes. Microarray technology was used to evaluate the expression of >4000 genes in a rat model of myocardial infarction. More than 200 genes were identified that showed differential expression in response to myocardial infarction. Gene expression changes were monitored from 2 to 16 weeks after infarction in 2 regions of the heart, the left ventricle free wall and interventricular septum. A novel clustering program was used to identify patterns of expression within this large set of data. Unique patterns were revealed within the transcriptional responses that illuminate changes in biological processes associated with myocardial infarction.

Animals↗

PubMed2000

Insulin-like growth factor-binding protein-3 induces fetalization in neonatal rat cardiomyocytes.

We employed cDNA microarrays representing 4000 distinct sequences to profile changes in gene expression in a rodent model of heart disease, namely, progression to heart failure after myocardial infarction. Differential gene expression in the left ventricle was examined at 4-week intervals over a 12-week period after coronary artery ligation in rats. Over this time course, insulin-like growth factor-binding protein-3 (IGFBP-3) was found to have a greater expression than in nondiseased tissues. We then employed quantitative real-time PCR to analyze gene expression in neonatal rat cardiac myocytes that had been treated with recombinantly expressed IGFBP-3 to examine a number of transcriptional responses designed to reflect the heart failure phenotype. The IGFBP-3 protein was shown to induce transcription of atrial natriuretic factor (ANF) and beta-myosin heavy chain (B-MHC). Analysis of conditioned media taken from IGFBP-3-treated cardiac myocyte cultures demonstrated an increase in ANF protein as well as in protein synthesis, as determined by metabolic incorporation of a radiolabeled amino acid. However, transcriptional changes of troponin-1, endothelin-1, or angiotensin-II by IGFBP-3 were not observed.

Angiotensin II↗

PubMed1999

Heparin-binding epidermal growth factor-like growth factor in hippocampus: modulation of expression by seizures and anti-excitotoxic action.

The expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), an EGF receptor ligand, was investigated in rat forebrain under basal conditions and after kainate-induced excitotoxic seizures. In addition, a potential neuroprotective role for HB-EGF was assessed in hippocampal cultures. In situ hybridization analysis of HB-EGF mRNA in developing rat hippocampus revealed its expression in all principle cell layers of hippocampus from birth to postnatal day (P) 7, whereas from P14 through adulthood, expression decreased in the pyramidal cell layer versus the dentate gyrus granule cells. After kainate-induced excitotoxic seizures, levels of HB-EGF mRNA increased markedly in the hippocampus, as well as in several other cortical and limbic forebrain regions. In the hippocampus, HB-EGF mRNA expression increased within 3 hr after kainate treatment, continued to increase until 24 hr, and then decreased; increases occurred in the dentate gyrus granule cells, in the molecular layer of the dentate gyrus, and in and around hippocampal pyramidal CA3 and CA1 neurons. At 48 hr after kainate treatment, HB-EGF mRNA remained elevated in vulnerable brain regions of the hippocampus and amygdaloid complex. Western blot analysis revealed increased levels of HB-EGF protein in the hippocampus after kainate administration, with a peak at 24 hr. Pretreatment of embryonic hippocampal cell cultures with HB-EGF protected neurons against kainate toxicity. The kainate-induced elevation of [Ca2+]i in hippocampal neurons was not altered in cultures pretreated with HB-EGF, suggesting an excitoprotective mechanism different from that of previously characterized excitoprotective growth factors. Taken together, these results suggest that HB-EGF may function as an endogenous neuroprotective agent after seizure-induced neural activity/injury.

Animals↗

PubMed1999

Case-based prediction in experimental medical studies.

Case-based approaches predict the behaviour of dynamic systems by analysing a given experimental setting in the context of others. To select similar cases and to control adaptation of cases, they employ general knowledge. If that is neither available nor inductively derivable, the knowledge implicit in cases can be utilized for a case-based ranking and adaptation of similar cases. We introduce the system OASES and its application to medical experimental studies to demonstrate this approach.

Animals↗

PubMed1999

Recombinant Kunitz protease inhibitory domain of the amyloid beta-protein precursor as an anticoagulant in venovenous extracorporeal circulation in rabbits.

Investigations were performed to characterize a recombinant Kunitz protease inhibitory domain of the amyloid beta-protein precursor (rKPI) as anticoagulants. After a single intravenous infusion of wild type rKPI into dogs, its elimination fit a two compartment model with a t1/2alpha and t1/2beta of 5 and 77 min, respectively. Further investigations determined if a variant form of rKPI with 178-fold more potent anti-factor Xa activity (rKPI-DD135, Ki = 0.9 nM) could serve as an anticoagulant in a rabbit model of extracorporeal circulation using a venovenous shunt. A prospective investigation was initiated to compare standard heparin (n = 8) at 400 U/kg with different infusion concentrations of rKPI-DD135. After a single intravenous infusion of 1.89 mg/kg of rKPI-DD135 followed by a constant infusion at 0.003 (n = 3), 0.03 (n = 7), or 0.3 (n = 5) mg/kg/min, the anti-factor Xa activity of the animals' plasma rapidly reaches a steady state for the two lower infusion concentrations of the agent. All infusions of rKPI-DD135 prolong the activated clotting time with less variation than that seen with heparin administration. rKPI-DD135 anticoagulation does not prevent a drop in the platelet counts. Fibrinogen levels decrease only slightly when the circuit is anticoagulated with rKPI-DD135. rKPI-DD135 markedly prolongs the APTT, has little effect on the PT, and reduces plasma prekallikrein and plasminogen activation. The 0.3 mg/kg/min infusion concentration of rKPI-DD135 results in reduced deposition of 111Indium-labeled platelets on the circuit when compared to heparin. Last, after a steady state level is achieved, 60% of the plasma anti-factor Xa activity of rKPI-DD135 is eliminated within 60 min after stopping the infusion. These data show the rKPI-DD135 can provide single agent anticoagulation in a rabbit extracorporeal circuit. Development of short acting factor Xa inhibitors may be useful anticoagulants for cardiopulmonary bypass.

Amyloid beta-Protein Precursor↗

PubMed1997

Heparin-binding EGF-like growth factor is a mitogen for rat alveolar type II cells.

Alveolar type II cells proliferate and differentiate into type I epithelial cells to restore the alveolar epithelium after lung injury. Since mitogens that bind the epidermal growth factor (EGF), EGF, receptor and transforming growth factor alpha (TGF alpha) have been shown to stimulate type II cell proliferation, studies were undertaken to determine whether the recently described protein, heparin-binding EGF-like growth factor (HB-EGF), was a mitogen for rat alveolar type II cells in primary culture. In addition, since HB-EGF is produced by macrophages, it was of interest to determine whether mitogenic activity for type II cells present in macrophage conditioned medium was due to HB-EGF. Rat and human recombinant HB-EGF stimulated thymidine incorporation into rat type II cells in a concentration-dependent manner up to 10-50 ng/ml then became inhibitory. The nuclear labeling index of type II cells increased from 2% to 16% with 10 ng/ml HB-EGF. However, HB-EGF induced only a small increase in cell number after 48 h and did not support low-density proliferation of alveolar type II cells. Conditioned medium from the human monocytic cell line, U937, stimulated type II cell DNA synthesis, and stimulatory activity could be partially purified by S-sepharose and heparin-sepharose chromatography. The growth-promoting activity from U937 cells that bound to heparin-sepharose was inhibited by a neutralizing antibody to human HB-EGF. Immunoblot analysis of active fractions also verified the presence of HB-EGF. However, the neutralizing antibody to rat HB-EGF did not inhibit mitogenic activity for type II cells found in rat bronchoalveolar lavage fluid. HB-EGF mRNA was found to be expressed in human alveolar macrophages to similar levels as differentiated U937 cells but was not detected in rat alveolar macrophages by Northern analysis of total mRNA. There was no difference in the level of HB-EGF mRNA expression in human alveolar macrophages from patients with interstitial lung disease compared with macrophages from normal subjects. The results demonstrate that HB-EGF is a mitogen for rat alveolar type II cells but appears to show species-specific differences with regard to its production by macrophages. Leslie, C. C., K. McCormick-Shannon, J. M. Shannon, B. Garrick, D. Damm, J. A. Abraham, and R. J. Mason. 1997. Heparin-binding EGF-like growth factor is a mitogen for rat alveolar type II cells. Am. J. Respir. Cell Mol. Biol. 16:379-387.

Adult↗

PubMed1996

U.S. experience with the AddVent VDD(R) pacing system. AddVent Phase I Investigators.

The AddVent pacemaker generator and model 1328C AV single-pass lead is a new pacemaker system capable of VDD or VDDR modes. The purpose of this study was to present the initial experience with AddVent in the United States and Canada. Between May 10, 1995 and May 3, 1996, 53 devices were implanted in 52 patients and followed for a mean of 217 (+/- 39) days. At the predischarge, 1-, 3-, and 6-month follow-up evaluations, atrial sensing thresholds and ventricular sensing and capture thresholds were measured in the supine, sitting, and standing positions to evaluate stability of atrial sensing with respect to body posture at rest. At the 1-month follow-up, a treadmill exercise test was performed to evaluate atrial sensing during exercise and to evaluate two new features of the AddVent called "sensor-mediated rate smoothing" and "preferential P wave sensing." Atrial sensing thresholds were not significantly different (P > 0.05) among body postures for any follow-up period or among follow-up periods for each posture. At rest, the percentage of appropriately tracked P waves observed was > 99% at each follow-up period. During treadmill exercise, the percentage of appropriately tracked P waves was > 98.7%. Appropriate preferential P wave sensing and sensor-mediated rate smoothing (VDDR mode) was observed. The AddVent pacing system provides safe and effective pacing therapy. Several features of VDDR pacing offer advantages over standard VDD pacing.

Aged↗

PubMed1996

Pharmacokinetics of levofloxacin in comparison to the racemic mixture of ofloxacin in man.

After oral administration of a single dose of 200 mg of levofloxacin and 400 mg racemic mixture of ofloxacin to 6 healthy male volunteers in a double-blind, randomised cross-over study, concentrations of the unchanged isomers were determined at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dosing was followed by a wash-out period of one week. Ofloxacin concentrations were determined using an enantioselective and a non-enantioselective high pressure liquid chromatography (HPLC) assay. The two measurements obtained were compared by linear distribution independent regression, and were found to be equivalent. Maximum serum concentration (Cmax) of levofloxacin after the administration of 200 mg of the levo-isomer was 2.42 mg/l (chiral derivatization HPLC, mean values); the corresponding area under the serum concentration-time curve (AUC0-28) was 17.0 mg x h/l. The corresponding Cmax values after the administration of 400 mg (+/-)-isomer (chiral derivatization HPLC and reversed phased HPLC, mean values) were 2.05 mg/l, 1.98 mg/l and 4.41 mg/l for (-)-, (+)- and (+/-) isomer, respectively. The AUCS0-28 were 17.0, 14.6 and 32.7 mg x h/l, respectively. The pharmacokinetics of the (-)- and (+)-isomer were shown to be almost equal. In serum and urine no reracemisation of the (-)-isomer to a racemic mixture was observed. General tolerability was good; no side effects were reported.

Adult↗

PubMed1995

Carboxyl-terminal truncation of leucine76 converts heparin-binding EGF-like growth factor from a heparin-enhancible to a heparin-suppressible growth factor.

Previous studies have indicated that heparin differentially regulates heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AR) mitogenic activity. To further explore this phenomenon, these mitogens were compared under identical cell culture conditions in two different assays. The results of our present investigation demonstrated that AR-mediated mitogenic activity in the murine AKR-2B fibroblast-like cell line was inhibited by heparin, while HB-EGF activity was enhanced. However, the absolute effect of heparin appeared to be cell type specific since HB-EGF mitogenic activity was not dramatically affected by coincubation with heparin when tested on human dermal fibroblasts. Several studies have indicated that mutation of a conserved leucine in the carboxyl-terminal region of both EGF and transforming growth factor-alpha results in decreased affinity for EGF receptors. Since this leucine is present in the analogous position of HB-EGF, but absent in AR, we examined the effect of deleting this residue by carboxyl-terminal truncation of HB-EGF. Analysis of recombinant forms of HB-EGF demonstrated that HB-EGF can be converted to a heparin-inhibited growth factor if the putative mature form of the protein is truncated by two residues (leucine76 and proline77) at the carboxyl terminus. Further analysis demonstrated that only leucine76 appears to be required for heparin-dependent enhancement of HB-EGF-mediated mitogenic activity, indicating that this amino acid may play a pivotal role in controlling the response of HB-EGF to heparin or related glycosaminoglycan sulfates. Our results also suggest that expression of different HB-EGF forms in vivo could result in the production of HB-EGFs with divergent responses to sulfated glycosaminoglycans and proteoglycans.

Amino Acid Sequence↗

PubMed1995

Accuracy and clinical utility of transtelephonic pacemaker follow-up.

The diagnostic accuracy of transtelephonic pacemaker monitoring (TTM) has been quantified in a retrospective study involving 369 patients in three U.S. cardiac centers. Using existing medical records, TTM findings in a total of 413 reports were judged for equivalence to the findings of subsequent physical examinations in pacemaker clinics. This study found TTM follow-up testing to have a sensitivity of 94.6%, specificity of 98.5%, positive predictive value of 93.3%, and negative predictive value of 98.8%. The study also documents the clinical utility of TTM in identifying various modes of pacemaker malfunctions and instances of significant arrhythmia.

Arrhythmias, Cardiac↗

PubMed1994

Biosynthesis and processing by phorbol ester of the cells surface-associated precursor form of heparin-binding EGF-like growth factor.

Human MDA MB 231 cells were found to synthesize mostly the cell surface-associated precursor form of heparin-binding EGF-like growth factor (HB-EGF), a 27-kDa protein. Evidence for this form of HB-EGF included increased fluorescence intensity when cells were analyzed by flow cytometry using anti-HB-EGF antibodies, lack of HB-EGF in conditioned medium, and sensitivity to diphtheria toxin, for which HB-EGF is the receptor. Phorbol ester treatment of cells resulted, within 30 minutes, in loss of cell surface 27 kDA HB-EGF, lack of interaction with anti-HB-EGF antibodies, accumulation of active 21 kDa HB-EGF in conditioned medium, and the acquisition of diphtheria toxin resistance. It was concluded that cell surface-associated HB-EGF is the precursor of a bioactive growth factor, is biologically active as the receptor for diphtheria toxin, and is susceptible to rapid processing.

Diphtheria Toxin↗

PubMed1994

Heparin-binding epidermal growth factor-like growth factor is an autocrine growth factor for human keratinocytes.

Since heparin-binding epidermal growth factor (HB-EGF) is a member of the EGF family and binds to EGF receptor, we tested recombinant HB-EGF for its ability to stimulate human keratinocyte proliferation. The effect of HB-EGF on human keratinocytes was dependent on the cell density. HB-EGF optimally increased the cell number by 1.8-fold at 1.0 ng/ml for a 4-day incubation period under subconfluent culture. In contrast, under confluent culture, 10 ng/ml HB-EGF optimally increased the DNA synthesis 2.1-fold. To examine the production of HB-EGF by human keratinocytes, the analysis of human keratinocyte-conditioned medium was undertaken by a combination of heparin affinity column chromatography, EGF receptor-stimulating assay, immunoblotting, and neutralization. Heparin column chromatography fractionated three activities, peaks 1, 2, and 3, which contained immunoreactive 30- and 27-, 19-, and 14.5-kDa bands, respectively. The anti-HB-EGF-blocking antibody neutralized the activities of peaks 2 and 3 by 38 and 22%, respectively, but did not neutralize the activity of peak 1 at all. The antibody reduced the cell growth by 37% for a 4-day incubation period. Northern blot analysis detected a 2.5-kilobase transcript of HB-EGF. The addition of 1 ng/ml HB-EGF optimally increased the levels of HB-EGF mRNA 5.4-fold at 1 h and TGF-alpha mRNA 3.1-fold at 3 h. Interestingly, the addition of TGF-alpha at 1 ng/ml to keratinocyte cultures enhanced the level of HB-EGF mRNA 10.2-fold at 6 h. 1 ng/ml EGF also increased HB-EGF mRNA levels 10.9-fold at 1 h. These results suggest that HB-EGF is an autocrine growth factor for human keratinocytes, and HB-EGF and TGF-alpha act not only by an autoinductive mechanism but also by mutual amplification.

Cell Division↗

PubMed1994

Characterization of sequences within heparin-binding EGF-like growth factor that mediate interaction with heparin.

Heparin-binding (HB) epidermal growth factor (EGF)-like growth factor (HB-EGF), a member of the EGF protein family, is a potent mitogen for fibroblasts, smooth muscle cells, and keratinocytes that was initially identified as a secreted product of macrophage-like cells. HB-EGF and EGF appear to act on target cells utilizing the same receptor, but HB-EGF is distinguishable from EGF by its strong affinity for heparin. To facilitate studies of structure-function relationships in HB-EGF, a bacterial recombinant expression system was established that produced biologically active HB-EGF with the expected disulfide bonding pattern. Mutagenesis and protease digestion studies of the recombinant HB-EGF, coupled with heparin-binding analyses of synthetic peptides, indicated that the sequences within HB-EGF mediating its interaction with heparin are located primarily in a stretch of 21 amino acids characterized by a high content of lysine and arginine residues. Most of this heparin-binding domain lies in an amino-terminal region of HB-EGF that has no counterpart in EGF, but a portion of the 21-residue sequence extends into the EGF-like region of HB-EGF. In addition, the mutagenesis and synthetic peptide studies indicated that sequences in HB-EGF lying outside of the 21-residue stretch can also influence the interaction with heparin. Finally, a synthetic peptide derived from the 21-residue stretch was found to compete with HB-EGF for binding to Chinese hamster ovary cells, suggesting that the heparin-binding sequences in HB-EGF may also mediate the interaction of this factor with cell surface heparan sulfate proteoglycan.

Amino Acid Sequence↗

PubMed1994

Heparin-binding EGF-like growth factor is a potent mitogen for rat hepatocytes.

We examined the hepatotrophic activity of heparin-binding EGF-like growth factor (HB-EGF), a recently identified potent mitogen for vascular smooth muscle cells and fibroblasts. HB-EGF stimulated DNA synthesis of rat hepatocytes in primary culture in a dose-dependent manner up to 30 ng/ml. The maximal stimulation by HB-EGF represented more than 80% of that induced by HGF. In normal rat liver, the transcript of HB-EGF gene was detected in the non-parenchymal cells and very low level in the hepatocytes. In the regenerating liver on the 3rd day after 70% hepatectomy, the HB-EGF mRNA increased in the non-parenchymal cells, suggesting that HB-EGF may contribute to liver regeneration through a paracrine mechanism.

Animals↗

PubMed1994

Necrosis in benign salivary gland neoplasms. Not necessarily a sign of malignant transformation.

Necrosis that occurs in a salivary gland neoplasm is usually considered to be an ominous sign, suggesting malignant transformation, particularly in lesions that have had no prior manipulation such as fine-needle aspiration. We describe five pleomorphic adenomas and two canalicular adenomas of salivary gland origin that exhibited necrosis, yet were otherwise benign. All lesions displayed a distinctive histopathologic pattern characterized by a narrow rim of viable tumor tissue at the periphery of the neoplasm combined with a diffuse central region that demonstrated apparent ischemic necrosis. No invasion of adjacent normal tissue was identified, and no recurrence or metastasis has been seen with these lesions. Caution should be exercised in the evaluation of salivary gland neoplasms with central necrosis to avoid misdiagnosis of all such lesions as malignant.

Adenoma↗

PubMed1994

Differential regulation of heparin-binding epidermal growth factor-like growth factor in the adult ovariectomized mouse uterus by progesterone and estrogen.

Expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) was studied in the adult ovariectomized mouse uterus in response to progesterone (P4) and/or 17 beta-estradiol (E2) using Northern blotting, in situ hybridization, and immunohistochemistry. A 2.5-kilobase transcript of HB-EGF messenger RNA (mRNA) was detected in total uterine RNA samples. Although low levels of this mRNA were detected in uterine samples of oil-treated ovariectomized mice (control), an injection of E2 promptly up-regulated the levels. The mRNA levels peaked at 2 h and returned to basal levels after 12 h. Injection of P4 alone did not influence the basal levels; however, coinjection of E2 with P4 caused a rapid, but transient, up-regulation of the mRNA. The levels peaked between 2-4 h and declined 6 h after the hormone injections. Coinjection of E2 with P4 after 1 day of P4 priming also resulted in peak levels of HB-EGF mRNA at 2 h; however, the levels were not sustained thereafter. Because P4 and E2 differentially regulate heterogeneous uterine cell types, in situ hybridization was performed to determine cell-specific expression of HB-EGF mRNA in the ovariectomized uterus before and after steroid treatments. In the oil-treated uterine sections, very low levels of autoradiographic signals were observed in the luminal epithelium. In contrast, an injection of E2 resulted in a marked accumulation of HB-EGF mRNA primarily in uterine epithelial cells within 2 h. Although specific hybridization signals could not be detected in any uterine cell types after P4 treatment, combined treatment with P4 and E2 resulted in an accumulation of HB-EGF mRNA in stromal cells. To determine whether uterine HB-EGF mRNA was translated, cellular distribution of HB-EGF protein was investigated by immunohistochemistry. In oil-treated uterine sections, an overall weak immunostaining was noted, whereas no staining could be detected in uterine sections after P4 treatment. In contrast, positive immunostaining was noted in epithelial cells after E2 treatment. Coinjection of P4 with E2 caused immunostaining in the stroma. These results are consistent with those of in situ hybridization. The present investigation establishes that in the adult ovariectomized mouse uterus, E2 regulates HB-EGF expression in the epithelium, whereas expression of HB-EGF in the stroma is regulated by P4 and E2.

Animals↗