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Biomedical subjects

K Lang

Publications and source records attributed to K Lang.

At least 55 records · Page 3Linked to original sources
PubMed1999

Optimum porphyrin accumulation in epithelial skin tumours and psoriatic lesions after topical application of delta-aminolaevulinic acid.

Photodynamic therapy with topically applied delta-aminolaevulinic acid is used to treat skin tumours by employing endogenously formed porphyrins as photosensitizers. This study examines the time course of porphyrin metabolite formation after topical application of delta-aminolaevulinic acid. Porphyrin biosynthesis in human skin tumours (basal cell carcinoma, squamous cell carcinoma), in psoriatic lesions, and in normal skin was investigated. Skin areas were treated with delta-aminolaevulinic acid, and levels of total porphyrins, porphyrin metabolites and proteins were measured in samples excised after 1, 2, 4, 6, 9, 12 and 24 h. There was an increase in porphyrin biosynthesis in all tissues with maximum porphyrin levels in tumours between 2 and 6 h and in psoriatic lesions 6 h after treatment. The pattern of porphyrins showed no significant difference between normal and neoplastic skin, protoporphyrin being the predominant metabolite. The results suggest that optimum irradiation time for superficial epithelial skin tumours may be as soon as 2 h after application of delta-aminolaevulinic acid, whereas for treatment of psoriatic lesions an application time of 6 h is more suitable.

Administration, Topical↗
PubMed1999

Multiple basal cell carcinomas associated with hairy cell leukaemia.

We report the case of a caucasian woman who, between the ages of 49 and 51 years, developed multiple (> 20) basal cell carcinomas (BCC). There was no family history of BCC. No abnormalities in the human homologue of the Drosophila segment polarity gene patched (PTCH), glutathione S-transferases T1 and M1, or cytochrome P450 1A1 were detected by polymerase chain reaction (PCR)-based molecular analysis. There was, however, actinic damage of the skin in sun-exposed areas. The patient was diagnosed as having hairy cell leukaemia (HCL) at the age of 51 years, based upon leucocyte morphology as assessed by light and electron microscopy, tartrate-resistant acid leucocyte phosphatase (TRAP) staining, fluorescence activated cell scanning of peripheral blood leucocytes and bone marrow histology. As the leukaemia slowly progressed over a 3-month period, the patient developed four further BCCs. Given that HCL is characterized by a profound defect in T-cell function, it is conceivable that T-cell immune dysregulation can contribute to the pathogenesis of BCC, possibly enhancing the aetiological effect of ultraviolet irradiation.

Basal Cell Carcinoma↗
PubMed1999

Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo.

Insulin-like growth factor-binding protein-5 (rhIGFBP-5) is stored in bone and stimulates osteoblast cell proliferation in vitro. Bone formation is dependent on the number and activity of osteoblasts. We therefore evaluated the ability of recombinant human (rh) IGFBP-5 to increase osteoblast activity in vitro; both alkaline phosphatase (ALP) activity and osteocalcin levels showed a dose-dependent increase. In in vivo time-course studies, daily s.c. administration of 50 microg rhIGFBP-5/day/mouse significantly increased serum osteocalcin levels by day 7, and these levels were sustained through day 21. We further evaluated whether rhIGFBP-5 was as effective as IGF-I. Daily s.c. administration of rhIGFBP-5 (50 microg/day), IGF-I (13 microg/day), or IGF-I plus rhIGFBP-5 complex for 9 days increased serum osteocalcin levels by 58%, 65%, and 81% (P < 0.001 in all) and femoral bone extract ALP activity by 85% (P < 0.001), 29% (P < 0.05), and 13% (P = NS), respectively, and decreased carboxyl-terminal cross-linked telopeptide of type I collagen by 29% (P < 0.05), 20% (P = NS), and 12.5% (P = NS), respectively. One s.c. injection of rhIGFBP-5 (50 microg/mouse) increased serum osteocalcin and bone ALP activity by 21% (P < 0.05) and 27% (P < 0.02), respectively, after 5 days, but did not significantly increase serum IGF-I (1, 6, or 24 h/postinjection), suggesting that the effects of rhIGFBP-5 on bone are not mediated by increasing circulating IGF-I. Our data demonstrate that systemic administration of rhIGFBP-5, either alone or in combination with IGF-I, increases bone formation parameters in vivo.

Alkaline Phosphatase↗
PubMed1999

The economic cost of Alzheimer's disease and related dementias to the California Medicaid program ("Medi-Cal") in 1995.

Although state Medicaid programs may bear a large portion of the costs of Alzheimer's disease (AD), current information on spending is not available. Using a health insurance claims database for a 10% random sample of California Medicaid ("Medi-Cal") recipients 60+ years of age, the authors estimated the excess cost of AD to Medi-Cal in 1995 as the difference in expenditures between an AD cohort (those with AD or related dementias) and an age- and sex-matched cohort without AD. Among 62,450 recipients, 2,575 (4.1%) were found to have AD or related dementias, and their average payments were approximately $7,700 higher (P<0.01) than those for the comparison group. These estimates suggest that Medi-Cal spends about $200 million on AD and related dementias annually, a burden that represents nearly 10% of state spending on elderly patients.

Aged↗
PubMed1999

Long-range electron transfer in rigid 3(10)-helical oligopeptides containing redox cyclic alpha-amino acids.

Intrahelical photoinduced electron transfer processes (ET) in conformationally restricted oligopeptides have been studied by nanosecond time-resolved transient spectroscopy. The helical peptides were constructed from sterically hindered alpha-aminoisobutyric acid (Aib) and two cyclic alpha-amino acids (Aib class) bearing electron acceptor and donor side chains (DkNap, ThQx). This helical backbone design provides high conformation stability, as previously demonstrated, and yields reliable 3(10)-helical architectures in solution. The forward ET between ThQx and 3DkNap is followed by a slow back ET thus giving rise to an accumulation of the charge-separated ion pairs for hundreds of nanoseconds. We demonstrate the modulation of electronic interactions by the number of intervening Aib residues separating acceptor-donor side chains and propose modifications of the peptide framework by inclusion of a non-Aib amino acid residue. These well-defined and sterically stable frameworks are suited for the precise evaluation of intrahelical electron transfer processes mediated by peptides.

Aminoisobutyric Acids↗
PubMed1999

[Treatment dropout as failed utilization--development of a predictive model for inpatient psychosomatic rehabilitation].

Premature discontinuance of rehabilitative measures can be considered a revised decision by the patient concerning participation or a revised decision by the clinic concerning admittance. Such termination of therapy suggests that the individual need for rehabilitation (defined as the fit between the patient's need for rehabilitation and the treatment offered by the rehabilitation facility) is not (or no longer) present, at least at this point in time. Assuming that the individual need for rehabilitation actually existed when treatment was requested or approval for rehabilitative measures was granted, the question arises as to when and how the need changed in such a way that would prevent the treatment from continuing as planned and being concluded in a regular fashion. This question will be taken into focus in the present article by developing a model for the prediction and explanation of prematurely discontinued treatment. This model will give central significance to the intention to co-operate, which is considered a dependent variable by reference to individual symptoms and treatment related expectations. Furthermore, various factors of influence during the stay in the clinic are formulated, which, firstly, have a presumed effect on the intention to cooperate and, secondly, have an influence on whether the intention to prematurely terminate treatment develops from a specific intention to cooperate and whether this is then realized. The model is discussed with regard to its practicability and possibilities for operationalization.

Germany↗
PubMed1998

Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions.

Binding proteins for insulin-like growth factors (IGFs) IGF-I and IGF-II, known as IGFBPs, control the distribution, function and activity of IGFs in various cell tissues and body fluids. Insulin-like growth factor-binding protein-5 (IGFBP-5) is known to modulate the stimulatory effects of IGFs and is the major IGF-binding protein in bone tissue. We have expressed two N-terminal fragments of IGFBP-5 in Escherichia coli; the first encodes the N-terminal domain of the protein (residues 1-104) and the second, mini-IGFBP-5, comprises residues Ala40 to Ile92. We show that the entire IGFBP-5 protein contains only one high-affinity binding site for IGFs, located in mini-IGFBP-5. The solution structure of mini-IGFBP-5, determined by nuclear magnetic resonance spectroscopy, discloses a rigid, globular structure that consists of a centrally located three-stranded anti-parallel beta-sheet. Its scaffold is stabilized further by two inside packed disulfide bridges. The binding to IGFs, which is in the nanomolar range, involves conserved Leu and Val residues localized in a hydrophobic patch on the surface of the IGFBP-5 protein. Remarkably, the IGF-I receptor binding assays of IGFBP-5 showed that IGFBP-5 inhibits the binding of IGFs to the IGF-I receptor, resulting in reduction of receptor stimulation and autophosphorylation. Compared with the full-length IGFBP-5, the smaller N-terminal fragments were less efficient inhibitors of the IGF-I receptor binding of IGFs.

3T3 Cells↗
PubMed1998

An in vitro test system for differentiation between antiproliferative and toxic effects in vascular smooth muscle cells.

We describe an in vitro test system looking for four endpoints in vascular smooth muscle cells (SMC): toxicity (cell number), DNA synthesis, reversibility of effects, and specificity of effects for SMC. SMC cultures at a low cell density, either actively proliferating or arrested by serum starvation and stimulated with 10% or 2% fetal calf serum (FCS) in parallel to treatment, are subject to a 52-h treatment phase with a test compound. Cultures were labeled with bromodeoxyuridine during the last 4 h of the treatment phase. Thereafter, the cultures are divided into two groups. In the first group, directly following treatment with a test compound, the cell number of the cultures is determined indirectly by using the vital dye neutral red. Subsequently, in the same cultures DNA synthesis is measured with an antibody directed to bromodeoxyuridine. The second group of cultures is reincubated with normal growth medium without test drug for a further 24 h. This recovery period is followed by determination of cell number and DNA synthesis as described above. This procedure allows determination of reversibility of effects observed directly after treatment giving important information for differentiation between toxic and antiproliferative mechanisms resulting in the reduction of DNA synthesis.

Animals↗
PubMed1998

Structure of interleukin 16 resembles a PDZ domain with an occluded peptide binding site.

The structure of a folded core of IL-16 is similar to that of intracellular protein modules called PDZ domains. IL-16 is thus the first extracellular protein found to have a PDZ-like fold. However, it does not exhibit normal peptide binding properties of PDZ domains. This is due to alterations of the structure at the 'PDZ-like binding site' of IL-16 (the GLGF cleft): the GLGF cleft of IL-16 is much smaller than those of PDZ-domains and is additionally blocked with a tryptophan side chain at its center. Our experiments indicate also that IL-16 nonspecifically aggregates in solution; but formation of a homo-tetrameric protein is not required, in contrast to previous suggestions, for its chemo-attractant activity.

Amino Acid Sequence↗
PubMed1998

Accelerated right colonic emptying after simulated upper gut hemorrhage.

OBJECTIVE: Upper gastrointestinal hemorrhage delays gastric emptying. Our aim was to evaluate the effect of gastrointestinal hemorrhage on small intestinal, ileocecal, and proximal colonic transit. METHODS: Healthy volunteers were randomized to receive either a duodenal infusion of heparinized autologous blood (n = 7) or egg white, acting as a control substance with similar composition; 1.5 mCi99mTc-DTPA was added to the infused substances. We infused 30 ml at an infusion rate of 1 ml/min. Gamma-camera images were taken for 4 h or until all radioactivity had entered the colon. Arrival of radiolabels in the colon and also counts in the ascending and transverse colon were quantified. RESULTS: Small intestinal and ileocecal transit were not significantly different between blood and egg white infusions. However, ascending colonic emptying was significantly faster after blood infusion compared to egg white. Four hours after the start of blood infusion a median of 30% of counts were in the transverse colon (11-50%; 25th-75th percentile) versus 0% (0-7%) after egg white infusion (p < 0.001). CONCLUSION: We concluded that simulated upper gastrointestinal bleeding hastens proximal colonic transit, but does not alter small intestinal transit and colonic filling.

Adult↗
PubMed1997

Molecular cloning, sequence, expression, and processing of the interleukin 16 precursor.

Interleukin 16 (IL-16) has been shown to function as chemoattractant factor, as a modulator of T-cell activation, and as an inhibitor of immunodeficiency virus replication. The recent identification of inconsistencies in published IL-16 cDNA nucleotide sequences led to the proposal that IL-16 is synthesized in the form of a large precursor protein (pro-IL-16). To identify the true transcriptional start of the IL-16 mRNA rapid amplification of cDNA ends methods were applied. The complete pro-IL-16 cDNA was subsequently molecularly cloned, sequenced, and expressed in COS-7 cells. We report here that pro-IL-16 is most likely synthesized as a 67-kDa protein and is encoded from a major 2.6-kb transcript. Recombinant pro-IL-16 polypeptides are specifically cleaved in lysates of CD8(+) cells, suggesting that the naturally secreted bioactive form of IL-16 is smaller than the originally published 130 amino acids fragment. Moreover, in contrast to other interleukins such as IL-15, IL-16 mRNA expression is almost exclusively limited to lymphatic tissues underlining the potential of IL-16 as an immune regulatory molecule.

Amino Acid Sequence↗
PubMed1997

Angiotensin-I-converting enzyme DD genotype is a risk factor of coronary artery disease.

Coronary artery disease (CAD) is a polygenic disease whose phenotypic manifestation depends on the interaction of a number of environmental factors. A number of genes, including the angiotensin-I-converting enzyme (ACE) gene, have been implicated in the pathogenesis of CAD. ACE could affect smooth muscle cell and fibroblast migration and proliferation, low-density lipoprotein (LDL) oxidation and endothelial cell function; these are all important factors in atherosclerosis. A polymorphic variant of the ACE gene correlates with higher circulating ACE levels and carries an increased risk of myocardial infarction, and cardiomyopathies. In this study, we sought to determine the distribution of ACE genotypes and the frequency of allele D in patients undergoing coronary angiography at our institution. DNA from 196 patients with angiographically proven CAD and 96 controls without CAD was amplified by polymerase chain reaction (PCR). The primers flanked the region of the ACE gene (intron 16) where the insertion (I) or deletion (D) of a 287-bp fragment results in the I/D polymorphism. PCR amplification of alleles I and D resulted in 490- and 190-bp products, respectively. In the control group, the relative allele frequencies of the polymorphism were similar to those of previously published European studies. The ACE genotype DD was present in 37.3% of patients with CAD as compared to 23.4% in the controls (p < 0.001, odds ratio 1.95, 95% confidence intervals (CI) 1.06-3.57). There was no association with the history of prior myocardial infarction. The genotype distribution in patients with single-vessel involvement was not significantly different from controls (p = 0.14). However, the DD genotype was significantly more common in patients having multivessel CAD when compared to single-vessel disease, indicating an association of this polymorphism with the extent of CAD. ACE genotype DD is more common in patients with multivessel CAD as compared to controls and to patients with single-vessel involvement, indicating that genotype DD is a genetic risk factor for extensive, multivessel CAD.

Aged↗
PubMed1997

Life-threatening dysrhythmias in severe thioridazine poisoning treated with physostigmine and transient atrial pacing.

OBJECTIVES: To describe clinical, electrocardiographic, and blood chemistry findings in a case of high-dosage thioridazine self-poisoning, focusing on the cellular mechanisms of the cardiovascular toxicity. DESIGN: Case report and literature review. SETTING: Intensive care unit (ICU) of a district hospital in Germany. PATIENT: A 68-yr-old male patient admitted to the ICU for treatment of a severe thioridazine intoxication. INTERVENTIONS: Prevention of absorption (gastric lavage), mechanical ventilation, fluids, alkalinization, catecholamines, drugs (physostigmine, neostigmine), direct current cardioversion/defibrillation, and transient pacemaker (atrial stimulation). MEASUREMENTS AND MAIN RESULTS: Central nervous, cardiovascular, and gastrointestinal systems indicated the adverse side effects of thioridazine intoxication over a period of 9 days. During high toxic thioridazine plasma concentrations (6061 to 6480 ng/mL), a life-threatening crisis occurred due to malignant ventricular arrhythmias followed by bradycardia (e.g., sinus node arrest). The electrocardiogram showed delays in all parts of the conduction system of the heart, including prolonged repolarization for several days, which disappeared completely when thioridazine plasma concentrations were within the therapeutic range. CONCLUSIONS: An individual therapeutic approach is needed in cases of thioridazine overdose. The primary aim is to stabilize the cardiac rhythm and the circulation.

Aged↗
PubMed1997

Integration of a knowledge-based system and a clinical documentation system via a data dictionary.

This paper describes the design and realisation of a knowledge-based system and a clinical documentation system linked via a data dictionary. The software was developed as a shell with object oriented methods and C++ for IBM-compatible PC's and WINDOWS 3.1/95. The data dictionary covers terminology and document objects with relations to external classifications. It controls the terminology in the documentation program with form-based entry of clinical documents and in the knowledge-based system with scores and rules. The software was applied to the clinical field of acute abdominal pain by implementing a data dictionary with 580 terminology objects, 501 document objects, and 2136 links; a documentation module with 8 clinical documents and a knowledge-based system with 10 scores and 7 sets of rules.

Abdominal Pain↗
PubMed1997

[Arterial and neural supply of the skin of the palm. Surgical-anatomical findings in Dupuytren's contracture].

It has been reported that the skin of the palm is supplied by arteries receiving their blood from a radial, thenar, ulnar, or hypothenar arterial system. Interestingly, the middle of the palm has been described as hypovascularized, but detailed informations on number and distribution of blood vessels are not available. By surgical treatment of the Dupuytrens contracture we could show that preservation of the blood vessels and nerves supplying the skin leads to excellent postoperative results. However, our intraoperative observations do not correspond to the picture of a poorly vascularized region of skin in the middle of the hand. During surgical treatment we found between six and nine bundles consisting of one artery, at least one vene, and one nerve in each case. The bundles perforate the palmar aponeurosis through channels, and subaponeurotically a lot of them originate from further proximal than expected. This information should be taken into consideration during the exstirpation of the palmar aponeurosis.

Adult↗
PubMed1996

Autocatalytic folding of the folding catalyst FKBP12.

Prolyl isomerases are folding enzymes and thus have the potential to catalyze their own folding. We show here that the folding of cytosolic FKBP12 (FK 506 binding protein) is an autocatalytic process both for the mature protein and for a fusion protein with an amino-terminal extension of 16 residues. Native FKBP contains seven trans-prolyl peptide bonds, and the cis-to-trans isomerizations of some or all of them constitute the slow, rate-limiting events in folding. The rate of an autocatalytic reaction increases with reactant concentration, because the product catalyzes its own formation. Accordingly, the folding of the fusion protein was more than 10-fold accelerated when the protein concentration was increased from 0.05 microM to 10 microM. At high concentrations of both forms of FKBP12 autocatalysis was very efficient, and the observed folding rate seemed to approach the rate of the fast direct folding reaction of the protein molecules with the correct (all trans) peptidyl-prolyl bond conformation.

Amino Acid Isomerases↗