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Biomedical subjects

M Vogt

Publications and source records attributed to M Vogt.

At least 55 records · Page 3Linked to original sources

Elevated serum leptin in patients with coronary artery disease: no association with the Trp64Arg polymorphism of the beta3-adrenergic receptor.

BACKGROUND: Serum leptin is associated with the occurrence of cardiovascular risk factors but it is unknown whether leptin is also associated with cardiovascular disease. Another open question is whether the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) is a determinant of circulating leptin. OBJECTIVES: We measured serum leptin concentrations in a large group of patients with angiographically assessed coronary artery disease (CAD) and investigated the relationship between the Trp64Arg polymorphism of the beta3-adrenergic receptor (AR) and serum leptin. PATIENTS AND METHODS: Leptin was measured in the fasting state in 1000 consecutive patients with angiographically confirmed CAD by radioimmunoassay. The codon 64 T/C polymorphism of the beta3-AR gene was analysed by the polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) technique. Controls were 1000 age-, gender- and weight-matched subjects without clinical signs of CAD. RESULTS: Serum leptin concentrations were significantly higher in patients with CAD than in those without CAD (median: 6.8 vs 6.1 ng/ml, P < 0.001). In a multiple regression analysis leptin was found to be a determinant of CAD (P = 0.005) along with established risk factors. No differences in serum leptin were observed between wild-type and heterozygous carriers of the Trp64Arg mutation of the beta3-AR gene, whereas the small group of homozygous carriers had higher leptin due to their higher BMI. In a multiple linear regression analysis, body mass index, gender and fasting insulin were the main significant determinants of serum leptin, whereas the beta3-AR polymorphism had no effect. CONCLUSIONS: Patients with coronary artery disease exhibit higher serum leptin concentrations than age- and gender-matched controls of comparable BMI, indicating that leptin could contribute to the development of cardiovascular disease, possibly via activation of the sympathetic nervous system. The Trp64Arg variant of the beta3-adrenoceptor did not influence serum leptin.

Aged↗

Axial strain imaging using a local estimation of the scaling factor from RF ultrasound signals.

The main signal-processing techniques used in elastography compute strains as the displacement derivative. They perform well for very low deformations, but suffer rapidly from decorrelation noise. Aiming to increase the range of accurate strain measurements, we developed an adaptive method based on the estimation of strains as local scaling factors. Its adaptability makes this method appropriate for computing scaling factors resulting from larger strains or a wide spread of strain variations. First, segments corresponding to the same part of tissue are adaptively selected in the rest and stressed state echo signals. Then, local scaling factors are estimated by iteratively varying their values until reaching the zero of the phase of the complex cross-correlation function. Results from simulation and from experimental data are presented. They show how this adaptive method can track various local deformations and its accuracy for strain up to 7%.

Algorithms↗

Growth factors improve muscle healing in vivo.

Injury to muscles is very common. We have previously observed that basic fibroblast growth factor (b-FGF), insulin growth factor type 1 (IGF-1) and nerve growth factor (NGF) are potent stimulators of the proliferation and fusion of myoblasts in vitro. We therefore injected these growth factors into mice with lacerations of the gastrocnemius muscle. The muscle regeneration was evaluated at one week by histological staining and quantitative histology. Muscle healing was assessed histologically and the contractile properties were measured one month after injury. Our findings showed that b-FGF, IGF and to a less extent NGF enhanced muscle regeneration in vivo compared with control muscle. At one month, muscles treated with IGF-1 and b-FGF showed improved healing and significantly increased fast-twitch and tetanus strengths. Our results suggest that b-FGF and IGF-1 stimulated muscle healing and may have a considerable effect on the treatment of muscle injuries.

Animals↗

Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening.

BACKGROUND AND METHODS: There are few data on the prevalence and clinical outcome of hepatitis C infection in children. We studied 458 children who underwent cardiac surgery in Munich, Germany, before 1991, when blood-donor screening for hepatitis C was introduced in Germany. Their mean age at first operation was 2.8 years; none of the children had received blood transfusions before or 'after cardiac surgery, and none of their mothers had antibodies to the hepatitis C virus (anti-HCV). We compared these patients with 458 control subjects matched for age and sex. RESULTS: Sixty-seven (14.6 percent) of the 458 patients who had undergone cardiac surgery had anti-HCV, as compared with 3 (0.7 percent) of the control subjects (P<0.001). At a mean interval of 19.8 years after the first operation, 37 (55 percent) of the 67 patients who were positive for anti-HCV had detectable HCV RNA in their blood. The infection had cleared in the other 30 patients, as evidenced by negative results on three polymerase-chain-reaction analyses performed at six-month intervals. Only 1 of the 37 patients who were positive for HCV RNA had elevated levels of liver enzymes; that patient had severe right-sided congestive heart failure. Of the 17 patients who underwent liver biopsies, only 3 had histologic signs of progressive liver damage. These three patients had additional risk factors: two had congestive heart failure, and the third had also been infected with hepatitis B virus. CONCLUSIONS: Children who had undergone cardiac surgery in Germany before the implementation of blood-donor screening for hepatitis C had a substantial risk of acquiring the infection. However, after about 20 years, the virus had spontaneously cleared in many patients. The clinical course in those still infected seems more benign than would be expected in people infected as adults.

Adult↗

[Gastrointestinal complications of diabetes mellitus].

BACKGROUND: Diabetes mellitus leads to a broad spectrum of symptoms and manifestations in the field of gastroenterology. BASIS: This article reviews the pathophysiology, differential diagnoses and secondary diseases of the gastrointestinal tract in diabetic patients. CLINICAL APPEARANCE: Motility disorders, infectious complications, secondary diseases of the stomach, liver, pancreas, gall bladder, small and large bowel are considered and discussed. Diagnostic and therapeutic approaches for the management of diabetic enteropathy are presented. CONCLUSION: The new strategies in diagnosis and therapy for a successful prevention or treatment of gastrointestinal complications due to diabetes mellitus need good cooperation of clinical specialties.

Diabetes Mellitus↗

[Newer antibiotics--missed efficacy in false indications].

Various reports indicate conclusively that antibiotics are used much too frequently and physicians often prefer broad spectrum compounds for "safety reasons". Symptoms of viral infections of the respiratory tract such as fever, cough and runny nose are often reason enough to start antibiotic regimens leading to increased costs and finally to development of resistance. Some newly developed antibiotics, often with unique properties will be discussed in this paper emphasizing potential problems associated with their uncritical use.

Anti-Bacterial Agents↗

[Interventional catheter occlusion of the atrial septal defect of the secundum type--experiences with "CardioSeal" and "Angel Wings"].

Between July 1996 and July 1998, 34 patients (female n = 16, male n = 18) were scheduled for catheter--interventional occlusion (ASDO) of an atrium septum defect of secundum type (ASD II). Median age was 7.9 years (2.5-54.6), weight 23.1 kg (9-97). 9 defects were closed with "Angel Wings" (AW) and 25 ASD occlusions were attempted with "CardioSeal" (CS). 30 patients had simple ASD II, 3 persisting foramen ovale with suspected paradoxal cerebral embolization and 1 significant residual shunt at atrial level after corrective heart surgery for interrupted aortic arch type B. ASDO was successful in 31/34 cases (91%). One CS was removed surgically due to significant left to right shunt after release and two CS devices were withdrawn back into the sheath. Median ASD diameter was 11.9 mm (6-16), balloon occlusive diameter was 15 mm (6-20) and median left to right shunt was 40% (6-64%). On follow up minimal left to right shunt was seen in 5/31 patients (16%). In selected patients catheter--interventional ASDO may be a good alternative to surgical ASD closure.

Adolescent↗

Sonography of the skin at 100 MHz enables in vivo visualization of stratum corneum and viable epidermis in palmar skin and psoriatic plaques.

A main drawback of 20-25 MHz ultrasound units for skin imaging is their limited resolution. We used a transducer with a center frequency of 95 MHz and a resolution of 8.5 microm axially and 27 microm laterally - an almost 10-fold increase compared with 20 MHz. By means of a new scanning technology we reached a depth of field of 3.2 mm. We examined normal palmar skin, normal glabrous skin on the abdomen, the upper back, the calf and the dorsal forearm, and 35 lesions of psoriasis vulgaris. From 11 psoriatic plaques biopsies were taken for correlation with the sonograms. In normal palmar skin, the horny layer is represented as an echopoor band below the skin entry echo, traversed by echorich coils, which correspond to eccrine sweat gland ducts. The thickness of this band significantly increases after occlusive application of petrolatum. Its lower border is defined by an echorich line, representing the stratum corneum/stratum Malpighii-interface. Underneath, a second echopoor band is visible, which corresponds to the viable epidermis plus the papillary dermis, bordered by the scattered echo reflexes of the reticular dermis. This band is also visible in glabrous skin; however, the stratum corneum cannot be detected. In psoriatic lesions, the thickened horny layer appears echorich; after application of petrolatum, its echodensity decreases. Below, the acanthotic epidermis plus the dermis with the inflammatory infiltrate are represented as an echopoor band. There is an excellent correlation between the sonometric thickness of this band and the histometric thickness of the acanthosis plus the infiltrated dermis. Our results show that 100 MHz sonography is a valuable tool for in vivo examination of the upper skin layers.

Adult↗

Scaphotrapezoid arthritis: prevalence in thumbs undergoing trapezium excision arthroplasty and efficacy of proximal trapezoid excision.

Between June 1995 and May 1998, 37 patients underwent trapezium excision arthroplasty. Preoperative radiographic assessment for scaphotrapezoid arthritis was performed. At the time of surgery intraoperative inspection of the scaphotrapezoid joint allowed calculation of the true prevalence of arthritis as well as sensitivity and specificity of the radiographic diagnosis. The true prevalence of scaphotrapezoid arthritis was 62%. The sensitivity of the radiographic diagnosis was 44% and the specificity was 86%. Comparison of surgical results in 23 patients who underwent both trapezium excision arthroplasty and proximal trapezoid excision, with 14 patients who underwent the former procedure, only showed that there was no morbidity associated with the latter. Because of the potential that scaphotrapezoid arthritis may cause residual symptoms following trapezium excision arthroplasty, and in light of the low sensitivity of radiographs, routine intraoperative assessment of the joint is recommended so that proximal trapezoid excision can be performed if degenerative change is present.

Adult↗

[100 MHz sonography in the visualization of the palmar stratum corneum after application of various creams and ointments].

To visualise the effects of different topically applied substances on the stratum corneum in vivo by means of sonography, it is necessary to have an ultrasound unit with a much higher resolution than provided for by the 20 MHz scanners currently used in dermatology. We developed a workstation with a highly focussed transducer with a large bandwidth, providing a resolution of 9 microns axially and 27 microns laterally. Using this ultrasound unit, we investigated the effects of different creams and ointments in 10 persons on the palmar side of the distal finger segments (vaseline, a water-in-oil-emulsion, an oil-in-water-emulsion, 10% urea in an oil-in-water-emulsion and water). Sonograms were taken after an occlusion period of 0, 30, 60, 120, 180 and 240 min. In 100 MHz sonograms of palmar skin, the stratum corneum is represented as an echo-poor band below the echo-rich entry echo--the correlate of the interface between the coupling water and the horny layer. The echo-poor band is traversed by echo-rich coils, representing eccrine sweat gland ducts. It is separated by an echo-rich line from the viable epidermis, which is echo-poor as well. The topically applied substances differ in the time course of the swelling of the stratum corneum. After longer application all externals cause a significant thickening of the stratum corneum (p < 0.005) and a reduction of the echogenicity of the skin entry echo due to altered impedance. 100 MHz sonography is well suited to visualise and quantify the effects of externals on the stratum corneum in vivo.

Administration, Topical↗

Oxidative stress and hypoxia/reoxygenation trigger CD95 (APO-1/Fas) ligand expression in microglial cells.

Apoptosis plays an important role in neurodegeneration, although the mechanisms and mediators in the brain are largely unknown. Because microglial cells have been suggested to contribute to apoptosis in neurological disorders, we investigated the expression of the death ligand CD95L in this cell type. We found that, compared to classical mediators of microglial activation, the most potent inducer of CD95L was oxidative stress. Exposure of microglial cells to H2O2 or paraquat rapidly triggered CD95L mRNA and protein expression, associated with the activation of transcription factor NF-kappaB. Enhanced expression of CD95L was further found following exposure of cells to hypoxia and subsequent reoxygenation. Our results indicate a potential role of CD95L in oxidative stress-mediated cell death, ischemia/reperfusion and other diseases with a disturbed redox balance.

Animals↗

[Erroneous intravenous injection of adrenaline].

HISTORY AND CLINICAL FINDINGS: Since a car accident a 29-year-old man had been suffering from chronic pain treated with injections of morphine and tilidine. Because of renewed worsening of pain he went to the emergency doctor who by mistake intravenously injected 1 mg of undiluted adrenaline. The patients immediately collapsed and pulmonary oedema developed. INVESTIGATIONS: On admission he was hypotensive (85/45 mmHg) and tachycardic (135/min), respiratory rate 36/min. Moist rales were heard throughout the lung. The white cell count was elevated and serum potassium low (3.5 mmol/l). but other routine laboratory tests were unremarkable. TREATMENT AND COURSE: Furosemide, nitroglycerin and morphine were injected at once and his general state improved over the subsequent few hours. Chest radiogram on the next day demonstrated marked reduction of the pulmonary oedema. CONCLUSION: To prevent similar, potentially lethal, accidents, before every i.v. injection two persons should check the name of the drug on the label of the vial or bottle, both on drawing up and before injecting the drug.

Adult↗

Role of reactive oxygen intermediates in activation-induced CD95 (APO-1/Fas) ligand expression.

Activation-induced cell death of T lymphocytes requires the inducible expression of CD95 (APO-1/Fas) ligand, which triggers apoptosis in CD95-bearing target cells by an autocrine or paracrine mechanism. Although execution of the CD95 death pathway is largely independent of reactive oxygen intermediates, activation-induced cell death is blocked by a variety of antioxidants. In the present study, we investigated the involvement of redox processes in the regulation of CD95 ligand (CD95L) expression in Jurkat T cells. We show that various antioxidants potently inhibited the transcriptional activation of CD95L following T cell receptor ligation or stimulation of cells with phorbol ester and ionomycin. Conversely, a prooxidant such as hydrogen peroxide alone was able to increase CD95L expression. As detected by Western blot and cytotoxicity assays, functional expression of CD95L protein was likewise diminished by antioxidants. Inhibition of CD95L expression was associated with a decreased DNA binding activity of nuclear factor (NF)-kappaB, an important redox-controlled transcription factor. Moreover, inhibition of NF-kappaB activity by a transdominant IkappaB mutant attenuated CD95L expression. Our data suggest that, although reactive oxygen intermediates do not act as mediators in the execution phase of CD95-mediated apoptosis, they are involved in the transcriptional regulation of CD95L expression.

Antioxidants↗

[Status febrilis and jaundice].

A 49 year old patient was admitted with fever and jaundice. Laboratory evaluation showed leukocytosis, elevated values for C-reactive protein, transaminases, bilirubin and alkaline phosphatase. Ultrasound and subsequent CT-scan revealed multiple liver lesions and a liquid mass in the bursa omentalis. A CT-guided catheter-drainage was performed and streptococcus milleri isolated from the abscess and one blood culture. After empiric broad spectrum treatment with Piperacillin/Tazobactam (Tazobac) and Netilmicin (Netromycin), Ceftriaxon (Rocephin) was given for a total treatment time of 10 days. Further evaluation revealed a perforated peptic ulcer as possible etiology for the described localized infectious complication.

Abdominal Abscess↗

Mutational analysis of disulfide bonds in the trypsin-reactive subdomain of a Bowman-Birk-type inhibitor of trypsin and chymotrypsin--cooperative versus autonomous refolding of subdomains.

It is widely believed that protein folding is a hierarchical process proceeding from secondary structure via subdomains and domains towards the complete tertiary structure. Accordingly, protein subdomains should behave as independent folding units. However, this prediction would underestimate the well-established structural significance of tertiary context and domain interfaces in proteins. The principal objective of this work was to distinguish between autonomous and cooperative refolding of protein subdomains by means of mutational analysis. The double-headed Bowman-Birk inhibitor of trypsin and chymotrypsin of known crystal structure was selected for study. The relative orientation of the two subdomains is stabilized by intramolecular and water-mediated hydrogen bonds and close ion pairs across a polar domain interface. The binary arrangement of a trypsin-reactive and a chymotrypsin-reactive subdomain facilitates the distinction of local and global irregularities in the mutants of this protein by means of functional assays. The functional consequences of five replacements in the S-S bond framework of the trypsin-reactive subdomain are analyzed in the present report. The mutants were subjected to refolding experiments in a refolding buffer and on trypsin-Sepharose as a template with complementary structure leading into a fully active state. The stability of the variants was assessed by means of subsequent equilibration experiments in solution. The mutants may be grouped into the following two classes: the class-I mutations located within beta-strand A are characterized by a breakdown of the trypsin- and the chymotrypsin-reactive subdomain upon refolding in solution and a complicated behavior in the equilibration experiments; by contrast, the Class-II mutations (beta-strand B) display rather local perturbations and a reversible return to the initial ratio of the two subdomains. This points to a significance of polar interactions connecting the beta-strand A of the trypsin-reactive with the chymotrypsin-reactive subdomain. In conclusion, the polar domain interface appears as a major refolding unit of the Bowman-Birk inhibitor.

Amino Acid Sequence↗

Sesquiterpene lactones specifically inhibit activation of NF-kappa B by preventing the degradation of I kappa B-alpha and I kappa B-beta.

Extracts from certain Mexican Indian medicinal plants used in traditional indigenous medicine for the treatment of inflammations contain sequiterpene lactones (SLs), which specifically inhibit the transcription factor NF-kappa B (Bork, P. M., Schmitz, M. L., Kuhnt, M., Escher, C., and Heinrich, M. (1997) FEBS Lett. 402, 85-90). Here we show that SLs prevented the activation of NF-kappa B by different stimuli such as phorbol esters, tumor necrosis factor-alpha, ligation of the T-cell receptor, and hydrogen peroxide in various cell types. Treatment of cells with SLs prevented the induced degradation of I kappa B-alpha and I kappa B-beta by all these stimuli, suggesting that they interfere with a rather common step in the activation of NF-kappa B. SLs did neither interfere with DNA binding activity of activated NF-kappa B nor with the activity of the protein tyrosine kinases p59fyn and p60arc. Micromolar amounts of SLs prevented the induced expression of the NF-kappa B target gene intracellular adhesion molecule 1. Inhibition of NF-kappa B by SLs resulted in an enhanced cell killing of murine fibroblast cells by tumor necrosis factor-alpha. SLs lacking an exomethylene group in conjugation with the lactone function displayed no inhibitory activity on NF-kappa B. The analysis of the cellular redox state by fluorescence-activated cell sorter showed that the SLs had no direct or indirect anti-oxidant properties.

Animals↗

APM-1, a novel human gene, identified by aberrant co-transcription with papillomavirus oncogenes in a cervical carcinoma cell line, encodes a BTB/POZ-zinc finger protein with growth inhibitory activity.

Integration of human papillomavirus (HPV) DNA into the host cell genome is an important step in cervical carcinogenesis. In tumour cells with integrated HPV DNA, transcription of viral oncogenes E6 and E7 continues into the flanking cellular sequences thereby producing viral-cellular fusion transcripts. Analysis of cellular sequences flanking the integrated HPV68 DNA in the cervical carcinoma cell line ME180 revealed homozygosity of the mutant allele in ME180 cells. We speculated that this could indicate the existence of a cellular tumour suppressor gene in the integration region. We report here the identification of a novel human gene, named APM-1, which is co-transcribed with the HPV68 E6 and E7 genes and is present in the 3'-cellular part of the ME180 viral-cellular fusion transcripts. The APM-1 gene encodes a protein with a BTB/POZ domain and four zinc fingers, and is located at chromosome 18q21. APM-1 transcripts are detected in normal cervical keratinocytes, but not in the majority of cervical carcinoma cell lines analysed. The APM-1 gene caused a reduction of clonal cell growth in vitro of HeLa and CaSki tumour cells. These characteristics make APM-1, the first novel human gene identified in a HPV integration region, a likely candidate for the postulated tumour suppressor gene.

Alleles↗