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T Fink

Publications and source records attributed to T Fink.

53 records · Page 3Linked to original sources
PubMed1993

Regional specificities in the distribution, chemical phenotypes, and coexistence patterns of neuropeptide containing nerve fibres in the human anal canal.

Despite the pivotal clinical significance of the human anal canal, little is known about its total and specific innervation. This study assessed the comparative distribution and histotopology of nerve fibres immunoreactive for neural markers and a variety of regulatory active neuropeptides in the human anal canal by light microscopic immunohistochemistry. Depending on the epithelial zone and region of the anal canal, the neural elements were differentially immunoreactive for the pan-neural marker protein gene product 9.5, the catecholamine marker tyrosine hydroxylase, the neuroendocrine marker chromogranin A, and various neuropeptides. Protein gene product 9.5-immunoreactive nerve fibres were ubiquitously abundant in the anal canal. In the anal transitional zone, ectopic epithelial types were supplied by the same pattern of peptidergic nerves as the respective type of epithelium in normotopic location. In the dermis of the squamous zone and in the perianal epidermis, unusual distribution patterns of nerve fibres, referred to as areas of high nerve fibre density, were encountered. Double immunohistochemistry revealed region-specific coexistence patterns of neuropeptidergic nerve fibres, and novel peptide coexistence patterns were detected in anal nerve fibres. Subsets of nerve fibres formed close spatial relationships with chromogranin A-positive neuroendocrine cells, most frequently in the anal transitional zone. Chromogranin-A positive cells were shown to be present in the epithelium of perianal eccrine sweat glands. The differential distribution, peptide phenotypes and coexistence patterns of different nerve fibre populations in the human anal canal may reflect topospecific regulatory functions of neurally released neuropeptides in health and disease.

Aged↗
PubMed1993

Analysis of human extrachromosomal DNA elements originating from different beta-satellite subfamilies.

By screening total human DNA with probes derived from the small polydisperse circular (spc) DNA fraction of cultured human cells, we identified three clones that carry long stretches of beta-satellite DNA. Further experiments have shown that the three sequences belong to at least two different beta-satellite subfamilies, which are characterized by different higher order subunits. Members of one of these subfamilies are located in the cytological satellites of all acrocentric chromosomes, whereas members of another are located on the short arms of the acrocentrics on both sides of the stalk regions and also in the centromeric regions of chromosomes 1 and 9. This is the first time that beta-satellite sequences obtained from the spcDNA of human cells have been assigned to beta-satellite subfamilies that are organized as long arrays of tandemly arranged higher order monomers. This indicates that beta-satellite sequences can be excised from their chromosomal loci via intrastrand-recombination processes.

Base Sequence↗
PubMed1993

The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic organization.

Mice carrying a retroviral insert in both alleles of the Mpv17 gene develop glomerulosclerosis and nephrotic syndrome at young age. Thus, the Mpv17 gene is a recessive disease gene in mice and this mouse strain is a potential animal model for glomerular diseases in man. We here describe the isolation and analysis of a human homolog of this gene. By interspecies hybridisation cDNA clones representing a single RNA species were isolated from human liver. Sequence analysis revealed over 90% identify in a region coding for a protein of 176 amino acids and unknown function in both species. Cloning of the genomic locus revealed a single copy gene which we mapped to the short arm of chromosome 2 at band 2p23-p21. Determination of the intron-exon structure and the junction sequences enabled us to establish a PCR based procedure to isolate the coding region from human genomic DNA. Thus, it is now possible to analyse patients suffering from candidate diseases on the basis of a blood sample if biopsy material is not available.

Animals↗
PubMed1991

A new multisequence family in human.

By hybridizing total human DNA with probes derived from the extrachromosomal circular DNA fraction of cultured cells, we detected a human multisequence family, called chAB4, previously unknown. Approximately 50 copies of this sequence are located in the haploid human genome. The repetition units of chAB4 are 35 kb long and the units are tandemly arranged. DNA sequence analysis of parts of the chAB4 unit revealed no direct evidence for a possible function of the family, but possibly chAB4 harbors a gene. Family members are located on human chromosomes 1, 3, and 9 and on the short arms of chromosomes 13-15, 21, and 22. Therefore, in addition to the rDNA, chAB4 is the second class of clustered repetitive sequences with a relatively long repetition unit localized on the short arms of all acrocentric chromosomes. Some evolutionary aspects arising from the structure of chAB4, the established parts of its DNA sequences, and the chromosomal localization of this new multisequence family are discussed.

Autoradiography↗
PubMed1991

Molecular anatomy of the neuro-immune connection.

Light microscopic immunohistochemistry was employed to elucidate and compare the presence, distribution, and coexistence of various peptides, neuroendocrine markers and enzymes of the catecholamine pathway in nerves supplying lymphoid tissues in a variety of mammalian species. All lymphoid organs and tissues receive innervation by fibers containing dopamine-beta-hydroxylase and/or tyrosine hydroxylase, neural markers like protein gene product 9.5, synaptophysin and neurofilament and a varied spectrum of peptides. The prominent peptides were tachykinins (substance P, neurokinin A), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI). Opioid innervation was variable. Double immunofluorescence revealed coexistence of tachykinins and CGRP and of tyrosine hydroxylase and NPY. A minor proportion of fibers showed coexistence of NPY and tachykinins and of VIP/PHI and tachykinins. The possible importance of the complex peptidergic innervation of lymphoid tissues in inflammation, allergy, inflammatory pain and psycho-neuro-immuno-endocrine network function is discussed. A special immunomodulatory role of the sensory neurons is suggested.

Animals↗
PubMed1991

Gene structure and chromosomal localization of the murine lamin B2 gene.

The structure of the murine lamin B2 gene has been analyzed by cloning, sequencing and hybridization techniques, including in situ hybridization. The gene exists in single copy on the distal arm of chromosome 10 and comprises at least 15 kb, containing 12 exons and 11 introns. The transcriptional start point, as determined by primer extension analysis and RNase protection, was mapped to the region -264 to -254 upstream the ATG start codon. The 5' upstream region does not reveal any classical TATA box elements but typical features of genes encoding "housekeeping" proteins. The intron pattern is strikingly similar to those of the Xenopus laevis lamin LIII (Döring, V., R. Stick, EMBO J. 9, 4073-4081 (1990)) and of the intermediate filament protein of the invertebrate Helix aspersa (Dodemont, H., D. Riemer, K. Weber, EMBO J. 9, 4083-4094 (1990], particularly in the central rod and in the tail domains. Moreover, this lamin gene contains an additional intron in the region encoding the rod domain. Our data are compatible with the evolutionary hypothesis that IF proteins have evolved from a lamin-like ancestor molecule.

Amino Acid Sequence↗
PubMed1989

Tachykinins, calcitonin gene-related peptide and neuropeptide Y in nerves of the mammalian thymus: interactions with mast cells in autonomic and sensory neuroimmunomodulation?

By the use of light microscopic (LM) immunohistochemistry the distribution of tachykinin (TK)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity in nerves supplying the mammalian (rat, mouse, guinea-pig, cat) thymus gland has been determined. There were no interspecies variations. Fibres staining for TK and CGRP completely overlapped indicating coexistence. They were present in the capsule, in interlobular septa and in the corticomedullary boundary and occurred in perivascular and paravascular plexus supplying arteries, veins and the microvasculature. Some TK/CGRP-immunoreactive (ir) fibres travelled between lymphoid cells and close contacts with mast cells were frequent. NPY-ir fibres were different from those staining for TK/CGRP and predominated in the perivascular plexus of arterial blood vessels. Only very rarely they coursed in the lymphoid parenchyma. Intimate contacts of NPY-ir fibres with mast cells were less frequent than those of TK/CGRP-ir fibres. We conclude that the NPY innervation is mainly sympathetic noradrenergic while thymic nerves coding for TK and CGRP are most likely of sensory origin. These pathways may play a differential neuroimmunomodulatory role in the thymus, possibly via interaction with mast cells.

Adrenergic Fibers↗
PubMed1989

Restriction analysis of chromosomal sequences homologous to single-copy fragments cloned from small polydisperse circular DNA (spcDNA).

Restriction fragments from the fraction of small polydisperse circular DNA (spcDNA) were cloned in pBR322. The spcDNA was prepared from cell cultures derived from an angiofibroma of a patient with tuberous sclerosis (TS). Such cultures have been shown previously to contain increased amounts of spcDNA. Four cloned spcDNA fragments containing single-copy sequences were chosen to characterize the homologous chromosomal DNA segments by restriction analysis. When used as hybridization probes, these four fragments generate well-defined nonvariable patterns in the chromosomal DNA from healthy donors. The restriction patterns obtained with one of the fragments (D-C4) can best be interpreted by assuming the presence of two copies of the homologous sequences in chromosomal DNA. A second sequence, A-B4, occurs at least 30-50 times in the haploid human genome. In both cases the duplicated regions span relatively large segments of DNA.

Base Sequence↗
PubMed1988

Multiple neuropeptides in nerves supplying mammalian lymph nodes: messenger candidates for sensory and autonomic neuroimmunomodulation?

By the use of light microscopic (LM) immunohistochemistry, the presence of peptides and of dopamine beta-hydroxylase (DBH) in nerves supplying mammalian (guinea pig, rat, cat, pig, mouse, human) lymph nodes were examined. In all species, lymph nodes of various somatic and visceral regions were found to contain nerve fibers which stained for neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), substance P (SP), calcitonin gene-related peptide (CGRP) or DBH. SP- and CGRP-immunoreactive (ir) fibers completely overlapped and exhibited the widest distribution. They were present in perivascular, paravascular and many non-vascular fibers travelling in close contact with lymphoid cells. In contrast, NPY-ir fibers coincided with those staining for DBH, prevailed in perivascular plexus and only rarely branched off into lymphoid parenchyma. Alternate staining of adjacent sections revealed that SP/CGRP-ir fibers were different from NPY/DBH-ir fibers. The distribution of VIP-ir fibers was identical to that of PHI-ir fibers and partially overlapped with that of ir-NPY/DBH or ir-SP/CGRP fibers. We conclude that the NPY innervation of lymph nodes is sympathetic noradrenergic while nerves coding for co-existing SP and CGRP are most likely of sensory origin. The nerves containing co-existing VIP and PHI may be of heterogenous origin (sensory, cholinergic sympathetic, and/or parasympathetic). We suggest that these distinct sensory and autonomic peptidergic pathways linking the nervous system with the lymph nodes may play a differential role in bidirectional neuroimmunomodulation.

Adrenergic Fibers↗
PubMed1986

[Sex determination of cadaver material by the detection of specific nucleotide sequences of the Y chromosome following DNA cleavage].

A gene technological method of sex determination in cadaverous material is reported. The samples were taken from a child's corpse, which was nearly completely skeletonized after 1 year in water. From cells of the bone marrow the DNA was isolated and digested by restriction enzymes. A defined fragment of 2.12kb length was cleaved off by the endonuclease HaeIII in the presence of Y chromosomes. After agarose-gel electrophoresis of the DNA fragments, the specific sequence was detected by hybridization with the cloned, radioactively labelled complementary plasmide pHY2.1.

Autoradiography↗
PubMed1986

Co-existence of prodynorphin--opioid peptides and substance P in primary sensory afferents of guinea-pigs.

Light microscopic immunoenzymatic and immunofluorescence histochemistry revealed co-existence of opioid peptides with substance P in primary sensory neurons of all segmental dorsal root and trigeminal ganglia of guinea-pig. Sensory opioid peptides appeared to be exclusively processed from prodynorphin and include [Leu]enkephalin, neoendorphins, and dynorphin A. We suggest the presence of presynaptic opioid autoreceptors in primary sensory afferences.

Afferent Pathways↗
PubMedDate not supplied

Biological characterization of three novel variants of IFN-alpha 13 produced by human placental trophoblast.

Interferon (IFN)-alpha from the human placenta was cloned and expressed with the aim to study the antiviral, antiproliferative, and immunostimulatory activities. In the present study, we describe three previously unknown sequence variants of IFN-alpha 13 originating from the villous trophoblast. The first variant differed from IFN-alpha 13 by a Cys99Arg substitution and a 10-amino acid C-terminal deletion, which led to a severe reduction of the antiviral and antiproliferative potential. The second variant with a Glu32Tyr substitution also displayed diminished antiviral and antiproliferative properties, but to a lesser extent than the first clone. For the third variant, a Ser25Pro substitution in the N-terminal part of the protein and two substitutions in the C-terminal part of the protein, Arg126Gly and Ala140Gly, resulted in diminished antiviral but not antiproliferative properties. Regardless of the altered antiviral and antiproliferative properties, all sequence variants demonstrated natural killer (NK) cell stimulatory potentials paralleling that of prototype IFN-alpha 13. Further studies are needed to gain a better understanding of the functional significance of different IFN-alpha subtypes at the maternal-fetal interface, in particular in light of the controversial role the NK cells play in the positive outcome of pregnancy.

Animals↗