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Biomedical subjects

U Seifert

Publications and source records attributed to U Seifert.

At least 19 recordsLinked to original sources

Rupture of multiple parallel molecular bonds under dynamic loading.

Biological adhesion often involves several pairs of specific receptor-ligand molecules. Using rate equations, we study theoretically the rupture of such multiple parallel bonds under dynamic loading assisted by thermal activation. For a simple generic type of cooperativity, both the rupture time and force exhibit several different scaling regimes. The dependence of the rupture force on the number of bonds is predicted to be either linear, like a square root, or logarithmic.

Binding Sites↗

Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C.

As acute hepatitis C virus (HCV) infection is clinically inapparent in most cases, the immunologic correlates of recovery are not well defined. The cellular immune response is thought to contribute to the elimination of HCV-infected cells and a strong HCV-specific T-helper-cell (Th) response is associated with recovery from acute hepatitis C (ref. 2). However, diagnosis of resolved hepatitis C is based at present on the detection of HCV-specific antibodies and the absence of detectable HCV RNA, and detailed comparison of the humoral and cellular immune response has been hampered by the fact that patient cohorts as well as HCV strains are usually heterogeneous and that clinical data from acute-phase and long-term follow-up after infection generally are not available. We studied a cohort of women accidentally exposed to the same HCV strain of known sequence and found that circulating HCV-specific antibodies were undetectable in many patients 18-20 years after recovery, whereas HCV-specific helper and cytotoxic T-cell responses with an interferon (IFN)-gamma-producing (Tc1) phenotype persisted. The data indicate these HCV-specific CD4 + and CD8+ T cells are biomarkers for a prior HCV exposure and recovery. Because of undetectable antibodies against HCV, the incidence of self-limited HCV infections and recovery may be underestimated in the general population.

Antibody Specificity↗

Axonal expression sites of tyrosine hydroxylase, calretinin- and calbindin-immunoreactivity in striato-pallidal and septal nuclei of the rat brain: a double-immunolabelling study.

Besides the dopaminergic afferent projection system, calbindin (CALB)- and calretinin (CR)-immunoreactive fibres of intrinsic and extrinsic origin represent the most abundant axonal categories in the rat striatal and lateral septal areas. The question arises whether or not they may represent separate populations, or whether they form subgroups which co-express more than one of these antigens. Therefore, the present study is focused on the distribution patterns of the axons single-immunolabelled by the catecholaminergic marker tyrosine hydroxylase (TH), and on TH-immunoreactive axons displaying also CR- and/or CALB-immunoreactivity in double-immunostained sections. Striking differences were found between the patch and matrix compartments of the caudate-putamen (CP). Whereas the vast majority of TH-immunoreactive fibres in the patches and a patch-associated subcallosal layer co-expressed CR but not CALB, fibres mono-labelled by the TH-immunoreactivity were predominant in the matrix. The matrix-like regions of the core of nucleus accumbens (CACC), fundus striati (FS), the striatal cell bridges (CB) and the striatal part of olfactory tubercle (OTU) coincided in this respect with the matrix in CP. The absence of CR-immunoreactivity was also characteristic of the TH-immunoreactive fibres in the patch-like areas of the accumbal core, although a high number of separate CR-immunoreactive axons were present. In the shell of nucleus accumbens (SACC) which receives a rich catecholaminergic innervation, fibres co-expressing either one of the calcium-binding proteins were absent. The islands of Calleja (CJI) displaying a strongly TH-immunoreactive centre and a periphery of lower staining intensity, showed only a low number of TH-immunoreactive fibres co-expressing CR or CALB. The broad shell-like band of TH-immunoreactive axons between medial and lateral part of the septum was single-stained with the TH-immunoreactivity. In contrast, the TH-positive fibres forming basket-like arrangements around some neurons in the dorsal lateral septal nucleus co-expressed also CR, but not CALB. The results are discussed in view of the recent concepts of basal forebrain organization and the cytochemical characteristics of mesencephalic dopaminergic nuclei giving rise to the vast majority of the striatal and septal TH-immunoreactive fibre supply, in order to correlate the known projection patterns with the content of calcium-binding proteins in TH-immunolabelled fibres and presumed cells of origin. The TH-immunoreactive fibres in the striatal patches displaying CR- but not CALB-immunoreactivity may originate mainly from neurons in the ventral tier of pars compacta (SNC) and from the pars reticulata of substantia nigra (SNR) which show identical cytochemical properties. Axons in the matrix of CP and the accumbal core as well as in the islands of Calleja single-labelled by the TH-immunoreactivity or additionally containing CALB and CR may originate from neurons in the dorsal tier of mesencephalic nuclei like SN, pars compacta and ventral tegmental area. CR-containing TH-immunoreactive basket-like axon terminations in the dorsal lateral septal nucleus are likely to originate either from mesencephalic nuclei or from the supramammillary region.

Animals↗

Comparison of the rat dorsal and ventral striatopallidal system. A study using the GABA(A)-receptor alpha1-subunit and parvalbumin immunolabeling.

The ventral striatum is more closely related to limbic brain regions than the dorsal striatum in spite of the remarkable similarities in the structural organization between these two brain regions. The present study is focused on the comparison of ventral striatopallidal territories and the dorsal striatopallidal system regarding the GABA(A)-receptor alpha1-subunit and parvalbumin immunoreactivity, as these markers showed specific distribution patterns and coexpression sites in the more intensely studied dorsal regions. Our investigations revealed that: (1) Parvalbumin single-labeled cells and a moderate number of neurons single-labeled with the GABA(A)-receptor alpha1-subunit exist not only in the dorsal but also in the ventral striatum, including the striatal cell bridges. In addition, morphologically similar neurons positive for the alpha1-subunit were also found in the corpus callosum and anterior commissure. (2) A small number of double-labeled neurons was seen not only in dorsal but also in ventral striatal regions. Such cells were mainly located near the border with the globus pallidus and ventral pallidum. They are likely to represent a further type of striatal neuron. (3) The vast majority of neurons in the entopeduncular nucleus, the homologue of the primate internal globus pallidus segment, coexpressed alpha1-subunit and parvalbumin immunoreactivity, as reported previously for the other pallidal compartments. (4) The islands of Calleja adjoining the ventral pallidal extensions in the olfactory tubercle exhibited a strong alpha1-subunit immunoreactivity in the neuropil as well as somata single- or double-labeled for both markers. Our findings indicate that the dorsal and ventral striatopallidal compartments are similarly organized in general with respect to the occurrence and distribution of single- and double-labeled parvalbumin-immunoreactive and GABA(A)-receptor alpha1-subunit-immunoreactive neurons.

Animals↗

Thermally induced proliferation of pores in a model fluid membrane.

The growth of thermally induced pores in a two-dimensional model fluid membrane is investigated by Monte Carlo simulation. Holes appear in the membrane via an activated process, and their subsequent growth is controlled by an edge energy per unit length or line tension. The barrier height and line tension, together with a lateral tension, are the independent parameters of the model. In the resulting phase diagram, a rupture transition separates an intact membrane from a disintegrated state. The approach to the ruptured state shows distinct regimes. Reducing the barrier height at large line tension produces multiple, quasi-independent, small holes whose behavior is dominated by their edge energy, whereas at lower line tensions shape fluctuations of the holes facilitate their coalescence into a single large hole. At a small value of line tension and large barrier height, a single hole spontaneously permeabilizes the membrane in an entropically driven phase transition. Entropy dominates pore growth for line tensions not far below those measured for artificial vesicles. Permeabilization of lipid bilayers by certain peptides involves perturbing lipid-lipid cohesive energies, and our simulations show that at small line tensions the entropy of hole shape fluctuations destroys the model membrane's stability.

Algorithms↗

A rare case of bloody diarrhea: thrombosis of the V. mesenterica inferior following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy has become the standard treatment for symptomatic cholecystolithiasis. The most common complications, as current experiences show, are bleeding, bile duct injury and non-technical complications like pneumonia. In some individual cases ischemic lesions of bowel by injury or thrombosis of intestinal vessels are described. Here we report the rare case of intestinal venous thrombosis following laparoscopic cholecystectomy. The complication clinically appeared within 24 h after operation starting with bloody diarrhea and mimicking inflammatory bowel disease. The patient, a 41-year old man, was treated with high-dose heparin and could be discharged after 44 days without complaints. Coloscopy six months after the event showed a restitution ad integrum.

Adult↗

[Morphologic findings in fetuses and placentas of late abortion in the 2nd trimester].

To investigate possible causes of abortion (and intrauterine foetal death) we reviewed clinical and morphological data of foetuses and placentas morphologically from 830 spontaneous abortions seen during a 12 years period (1978-1989) at the Institute of Pathology, University of Leipzig, and the Pathological Institute of Hoyerswerda. Our review showed that definite and possible causes of foetal death and abortion could be classified as placental, foetal maternal, and clinical. Placental changes, which included infection of the foetal membranes, disturbances of the uteroplacental circulation (abruptio placentae with bleeding) and placental dysmaturity, were the most important causes and accounted for 73.8% of the cases. Foetal causes mainly comprised multiple twin pregnancies and foetal malformations. In 20 cases (2.4%) we found malformations as a cause of foetal death and consecutive abortion. Overall, malformations were found in 7.5% of the cases examined. Maternal and obstetric complications of pregnancy were less frequent. In 16.5% of our cases, the cause of the abortion or intrauterine death remained obscure. However, since 1989, genetic analysis and prenatal diagnostic procedures have improved, bringing a greater knowledge on the spectrum and aetiology of possible developmental disorders in the foetus. This should reduce the number of unexplained abortions.

Abortion, Spontaneous↗

[Rare initial manifestation and differential diagnosis of primary sclerosing cholangitis].

BACKGROUND: Primary sclerosing cholangitis is most often diagnosed in middle-aged men who are suffering from inflammatory bowel diseases. CASE REPORT: A young, previously healthy woman presents with icterus of acute onset, high transaminases and positive hepatitis B virus serology. Ultrasound and nuclear magnetic resonance images demonstrate multiple liver tumors. After acute viral hepatitis as well as primary or secondary malignant liver tumors have been excluded as underlying diseases, diagnosis of primary sclerosing cholangitis is made. CONCLUSION: Differential diagnosis of primary sclerosing cholangitis should also be considered in cases with untypical primary presentation.

Acute Disease↗

Serological pattern of hepatitis C virus recurrence after liver transplantation.

BACKGROUND/AIMS: Hepatitis C infection is characterized by a high incidence of liver cirrhosis, frequently requiring liver transplantation. After orthotopic liver transplantation, recurrence of hepatitis C virus infection is common, but often difficult to differentiate from allograft rejection. In this context the role and diagnostic value of hepatitis C virus-associated markers like the anti-GOR response have not yet been determined. In this study we analyzed the time course of hepatitis C virus recurrence in hepatitis C virus-infected patients who underwent liver transplantation because of end-stage cirrhosis or acute liver failure. METHODS: We evaluated the serological pattern and diagnostic significance of anti-HCV, anti-HCV-IgM, anti-HCV-core, anti-HCV-core 5-27, anti-GOR, anti-GOR-IgM and HCV-RNA in serial serum samples during hepatitis C virus recurrence with or without allograft rejection up to 5-64 months after orthotopic liver transplantation. For comparison, we also studied these markers in serial serum samples from previously uninfected patients who acquired hepatitis C virus-infection during or shortly after orthotopic liver transplantation. Hepatitis C virus-infected patients who had undergone orthotopic liver transplantation were identified by screening pre-transplant sera from 235 patients for the presence of anti-HCV (2nd generation ELISA) and serum HCV-RNA (reverse transcription polymerase chain reaction). RESULTS: Of 218 patients transplanted for end-stage liver cirrhosis, 65 (30%) were anti-HCV positive and 33 (15%) were HCV-RNA positive, while only one of 17 patients (6%) transplanted for acute liver failure was found to be anti-HCV positive without detectable HCV-RNA. Fifty-two hepatitis C virus-infected patients were studied serially before and after liver transplantation: 46 patients (89%) showed recurrent anti-HCV antibodies within 3 months and 51 patients (98%) within 42 months after orthotopic liver transplantation. Serum HCV-RNA was detected in 39 patients (75%) within 3 months and in 44 patients (85%) within 42 months after orthotopic liver transplantation. In the patients studied serially during hepatitis C virus-recurrence, anti-GOR antibodies displayed the same serological profile as hepatitis C virus antibodies, i.e. a decrease after orthotopic liver transplantation and slowly rising titers when HCV-RNA became detectable again. De novo infection with hepatitis C virus as studied in four patients produced a significant peak of anti-HCV titers accompanied or followed by an increase in anti-GOR titers, indicating that the immune response to GOR-autoantigen is triggered by the hepatitis C virus. No significant diagnostic difference between anti-GOR and anti-HCV was noted during hepatitis C virus recurrence and allograft rejection.

Amino Acid Sequence↗