Biomedical subjects

T Fink

Publications and source records attributed to T Fink.

At least 19 recordsLinked to original sources

PubMed2007

[An unusual complication after an insect bite? Diagnostic procedures in a case of granular cell tumor].

Granular cell tumors are, in almost all cases, benign soft tissue tumors, although malignant variants have rarely been described in a variety of anatomical locations. In the case presented here, a so-called atypical granular cell tumor was diagnosed based on two criteria, being differentiated from the usual histological findings by enhanced mitotic activity and focal spindle cell proliferation. Further suspicious characters of the tumor were its size of 13x10x5 cm on MRT as well as its long-term clinical course (1.5 years). The diagnostic procedures undergone until resection of the tumor, including the macroscopic and histological findings, are presented. The diagnosis can be made with certainty by using conventional histology in combination with immunohistochemistry. The tumor cells react positively with antibodies against S-100 protein, NSE, laminin, myelin proteins and myelin-associated glycoproteins. These staining patterns underscore the neural origin of the tumor tissue. In this case a mitotic frequency of two per ten high power fields and focal spindle cells led to the diagnosis of an atypical granular cell tumor, whereas the criteria for a malignant variant were not met.

Animals↗

PubMed2006

Randomised phase II study comparing topotecan/carboplatin administration for 5 versus 3 days in the treatment of extensive-stage small-cell lung cancer.

BACKGROUND: Topotecan is an active drug in small-cell lung cancer (SCLC). In our previous study, a combination of topotecan with cisplatin was associated with a median overall survival of 7.6 or 8.7 months, depending on the duration of treatment. We have replaced cisplatin by carboplatin in this trial, with the objective of creating a more convenient schedule for our patients. Furthermore, we have also compared the standard 5-day schedule with an experimental 3-day schedule. PATIENTS AND METHODS: A total of 100 patients with metastatic disease were included. Patients were randomly assigned to receive either topotecan 0.75 mg/m2, days 1-5, and carboplatin AUC 5, day 5 (arm A) or topotecan 1.25 mg/m2, days 1-3, and carboplatin AUC 5, day 3 (arm B). Six cycles were given at a 3-week interval. RESULTS: A total of 91 patients were assessable for response. The response during therapy was 86.9% in arm A and 80.0% in arm B. Median survival in arm A was 11.8 months and in arm B 11.6 months (P=0.37). CONCLUSIONS: The combination of topotecan and carboplatin is active in extensive-disease SCLC. Toxicity and median survival were comparable in both arms. Three days of treatment seems to be similar to the 5-day regimen.

Adolescent↗

PubMed2003

Expression of butyrate response factor 1 in HTLV-1-transformed cells and its transactivation by tax protein.

Tax oncoprotein of Human T-lymphotropic virus 1 (HTLV-1) has been proposed to dysregulate the expression of a number of cellular genes, many of which play a critical role for cell proliferation. Our initial data demonstrated that the immediate-early gene butyrate response factor 1 ( BRF1) was upregulated in HTLV-1-infected cells. The ensuing studies revealed that the effect of Tax was mediated through two transcription elements. The more proximal element, located in the vicinity of TATA box, accounted for the main Tax transactivating effect, and it appeared to be a novel transcription factor-binding site. It involved the CCTCCTC sequence (nt -59/-53, relative to transcription start site) and was dubbed BRF1 Tax-responsive site (BTRS). The cellular protein(s) recruited into the formation of DNA-protein complex at this binding site were not identified. The other element, located further upstream, was a consensus cAMP-responsive site (CRE) TGACGTCA, spanning positions -400 to -393. CRE-binding protein (CREB) was found to mediate the transactivating effect of Tax at this site. Our results present the first evidence that the Tax transactivator has a capability to modulate the expression of BRF1 and that this effect is mediated by CRE and a novel BTRS motifs.

Cell Line↗

PubMed2003

Natural killer cell-mediated basal and interferon-enhanced cytotoxicity against liver cancer cells is significantly impaired under in vivo oxygen conditions.

Current immunostimulatory treatment protocols of cancer are often met with little success. Several lines of evidence indicate that the tumour microenvironment may impair the cytotoxic activity of natural killer (NK) cells. In this study, the NK cell-mediated killing of liver-derived cells was investigated at oxygen concentrations conform to those present in the human body at physiological and pathological conditions. The in vivo-relevant oxygen concentrations corresponding to 1, 2 and 6% were compared to those of the ambient air (21%) for their effect on the lysis of four liver-derived cell lines and the highly susceptible K562 cells. Exposure to each of the hypoxic conditions had a significantly inhibitory effect on NK cytotoxicity. Treatment with interferon-alpha (IFN-alpha) in hypoxia enhanced the cytotoxic potential of the NK cells less than it enhanced the cytotoxicity at ambient oxygen conditions. In summary, the oxygen tension profoundly affects both the cytoxic activity of NK cells and their activation by IFN-alpha.

Cytotoxicity, Immunologic↗

PubMed2001

[Cross-over comparison of the pharmacokinetics of estradiol during hormone replacement therapy with estradiol valerate or micronized estradiol].

OBJECTIVE: The aim of this randomized cross-over study was the comparison between a sequential 28-day hormone replacement therapy (HRT) using micronized estradiol and a cyclic 21-day HRT using estradiol valerate with regard to the pharmacokinetics of estradiol. - MATERIAL AND METHODS: Fifty postmenopausal women were randomly assigned to be treated either with Trisequens(R) for 28 days or with Sisare(R) for 21 days. After a wash-out cycle, the women were treated for one cycle with the other preparation in a cross-over fashion. The pharmacokinetic profile of the serum concentrations of estradiol was measured on day 1, 21 and 28 each immediately before and 1, 2, 4, 6, 8, and 10 hours after intake of a tablet, and the AUC (area under the curve) was calculated. - RESULTS: The serum concentrations of estradiol increased from a mean of 10 pg/ml up to 40 pg/ml (Trisequens(R)) and 30 pg/ml (Sisare(R)) on day 1, and to 80 pg/ml (Trisequens(R)) and 60 pg/ml (Sisare(R)) on day 21, and declined to 40 pg/ml (Trisequens(R)) and 10 pg/ml (Sisare(R)) on day 28. The AUC as calculated from both treatment cycles, was significantly higher on day 1, 21, and 28 during treatment with Trisequens(R) than with Sisare(R). This difference was, however, not signifcant on day 1 and 21 of the first treatment cycle. - CONCLUSION: During treatment with 2 mg micronized estradiol the serum concentrations are significantly higher than with 2 mg estradiol valerate. On day 28 of treatment with Sisare(R), the estradiol levels decline to baseline values, while using Trisequens(R) they remain in the range of those measured on day 1.

Aged↗

PubMed2001

Quantitative gene expression profiles of human liver-derived cell lines exposed to moderate hypoxia.

AIMS: To obtain better understanding of molecular events following critical oxygen shortage in liver tissue, we performed a large-scale comparison of gene expression profiles in four human liver cell lines, Chang, Hep3B, HuH7, and HepG2. METHODS: We used Atlas cDNA expression arrays from Clontech for initial screening, and quantitative real-time RT-PCR to assess the statistical significance of observed changes. RESULTS: RT-PCR analysis confirmed significantly changed levels of 24 transcripts after 24 hours incubation in 1% O(2). Among the genes most robustly up-regulated were plasminogen activator inhibitor-1 (PAI-1), insulin-like growth factor binding protein-3, and glyceraldehyde-3-phosphate dehydrogenase. Only PAI-1 was concordantly up-regulated in all four cell lines. Conversely, most down-regulated were the stress response genes, including several heat shock proteins, yet only the expression of flap endonuclease-1 was significantly decreased in all cell lines. When comparing individual cell lines, the HepG2 cells displayed a pattern of general down-regulation (83%), followed by Hep3B with 58% of genes down-regulated. In the Chang and HuH7 cells, however, the expression of most genes, 50% and 67%, respectively, remained unchanged. CONCLUSION: These studies provide information that is of importance for improved insight into the responses of not only liver tumor cells but also normal liver tissue in the conditions where physiological oxygenation is severely impaired.

Carcinoma, Hepatocellular↗

PubMed2000

The organized subdural blood clot in forensic case work - a case report.

The medico-legal assessment of a subdural haematoma (recent or organized) usually requires some information regarding its cause. Quite often, especially in the absence of a known history of trauma, minor head injuries, which are no longer verifiable, are simply assumed to be the most likely causes. Considering the fact that a subdural haematoma could also be non-traumatic, e.g. in haemorrhagic disorders, cardiac conditions with persistent passive hyperaemia, true inflammatory and degenerative processes of the dura, etc., the medico-legal implication of a possible head injury would require the exclusion of such non-traumatic conditions capable of causing subdural bleeding. In this respect, the case of a 92-year-old man, who suffered from cerebral sclerosis with occasional episodes of confusion and agitation, is briefly discussed. He was reported to have fallen from his bed, was hospitalized and died 2 days later. A head injury was suspected. At autopsy, no skull fractures and no obvious bruises were discovered. Fresh bilateral temporal subdural haematomas were found. These appeared consistent with a suspected head injury sustained as a result of a fall. Fairly large partly organized adherent subdural clots in the parieto-occipital region completely remote from and unconnected with the fresh bitemporal haematomas were also found. Based on the gross pathology and the histology, an attempt is made to assess the possible cause of the organized clots. Some of the findings indicated a possible non-traumatic origin, a consideration which is likely to affect the forensic implications.

Accidental Falls↗

PubMed2000

Use of the software 'Poser4' in reconstruction of accident and crime scenes.

The reconstruction of accident and crime scenes demands the full attention of the forensic working physician. Description by words is often difficult and liable to be misunderstood. Reconstruction in the original places of events are expensive and in some cases impossible. Computer graphics and animations give the possibility to construct the original course of events. Poser4 is a software package to perform these reconstructions in an easy and vivid way. We investigated the possibilities of reconstructing an accident with this software.

Accidents↗

PubMed2000

Lack of protection against vertical transmission of HIV-1 by interferons produced during pregnancy in a cohort from East African republic of Malawi.

Interferons (IFNs) associated with pregnancy were studied for their possible role in inhibition of vertical transmission of the human immunodeficiency virus type 1 (HIV-1). A study group was composed of 43 HIV-1-positive mothers, of whom 15 transmitted the virus to the offspring and 28 did not. The control group included 48 HIV-1-negative mother-infant pairs. The IFN-alpha was detected only sporadically in the maternal sera from the groups of transmitters (27%), nontransmitters (21%), and controls (19%). The average levels of IFN-alpha were low, 16.3 +/- 2.5 pg/ml, 21.4 +/- 9.9 pg/ml, and 21.3 +/- 9.4 pg/ml among the transmitters, nontransmitters, and control subjects, respectively. In the cord blood, IFN-alpha was detected only on two occasions among transmitters, and on a single occasion in the control group. IFN-beta was absent from both maternal and cord blood in the study group, and found to be present in one case in the control group simultaneously in the maternal and fetal sera. In the placentas, on the other hand, both type I and II IFNs were expressed universally in the villous trophoblast, and IFN-alpha and -beta in the stromal macrophages as well. In one case among transmitters, no IFNs were detected; nevertheless, no significant difference with respect to nontransmitters could be confirmed. Our data suggest that although the placental IFNs have an antiviral potential, they are not sufficient to suppress transmission of HIV from mother to infant.

Chorionic Villi↗

PubMed1999

Genetic analysis reveals ongoing HIV type 1 evolution in infected human placental trophoblast.

To provide a better understanding of the role of placenta in vertical human immunodeficiency virus (HIV) transmission, we have studied the infection of placental trophoblast in a group of 15 mother-neonate pairs. By nested PCR amplification of the C2V3 env gene region, HIV-1 has been found to infect the placenta in five cases (33%). Phylogenetic analysis of the cloned sequences showed that all recovered maternal variants were of the B subtype. Further investigation into the ancestral relationships at the nucleotide level revealed that the trophoblast sequences evolved into a quasispecies population clearly distant from that observed in the mother. As expected, the populations transmitted to the trophoblast were also found to be more homogeneous than those in the mothers when characterized on the basis of pairwise nucleotide sequence distances. With regard to the predicted biological properties, the primary amino acid structure of the V3 loop domain was consistent, with a macrophage-tropic, non-syncytium-inducing phenotype in all patients. We also attempted to determine if any of a number of selected maternal or viral factors was associated with trophoblast infection. However, none of the followed parameters, including maternal age, disease stage, antiretroviral therapy, CCR5delta32 deletion status of the infant, and viral genotype, could be associated with viral transmission. Moreover, in one pair with proven trophoblast infection, HIV was also detected in the cord blood. Taken together, our data suggest that the productive trophoblast infection by HIV-1 in vivo is a relatively frequent event that may bear direct implications for a further transplacental propagation of the virus.

Adult↗

PubMed1999

Neuroimmune appendicitis.

BACKGROUND: 15-25% of appendices removed from patients with suspected appendicitis appear normal on histological examination. The cause of pain in such patients is unknown. Since the content of neuropeptides seems to be altered in chronic inflammation, we investigated possible changes in peptidergic innervation for substance P (SP), vasoactive intestinal peptide (VIP), and growth-associated protein-43 (GAP-43). METHODS: Appendices classified as showing acute appendicitis, non-acute appendicitis (clinical signs of acute appendicitis, but histologically not inflamed), or normal were processed for SP, VIP, and GAP-43 immunocytochemistry. The density of SP immunostaining was assessed by digitised morphometry. FINDINGS: 31 appendix specimens were studied (16 acute, 15 non-acute). 16 specimens were used as controls. Expression of GAP-43 was increased in the non-acute appendices. We observed larger amounts of SP-immunoreactive and VIP-immunoreactive nerves in the mucosal layer of the appendix in patients with non-acute appendicitis than in controls and patients with acute appendicitis (mean % area SP-immunoreactive 0.0496 [SD 0.0113] non-acute, 0.0221 [0.0049] acute, 0.0229 [0.0068] controls). In addition, a close spatial relation between SP-immunoreactive and VIP-immunoreactive nerve fibres and lymphoid cells was detected in the outer zone of lymph follicles. INTERPRETATION: Neuroproliferation in the appendix, in association with an increase in neurotransmitters SP and VIP, may be involved in the pathophysiology of acute right abdominal pain in the absence of an acute inflammation of the appendix. Our data, together with increasing knowledge about the way in which the nervous system and immune cells interact, suggest that neuroimmune appendicitis is a distinct pathological entity.

Abdominal Pain↗

PubMed1999

Glutaminergic and adrenergic receptors expressed on adult guinea pig Schwann cells in vitro.

We have investigated the responsiveness of adult guinea pig Schwann cells to a range of neuroligands, using ratiometric calcium imaging. The majority of cells responded to ATP (90 +/- 4%), adrenaline (57 +/- 5%), and noradrenaline (61 +/- 5%), as well as glutamate (60 +/- 5%). The number of cells responding to glutamate increased significantly (90 +/- 4%; p < 0.01) when the cells were grown in excitatory amino acid (EAA) free medium, indicating EAA-induced downregulation. Only a small number of cells (9 +/- 2%) responded to acetylcholine. Agonist and antagonist experiments show that these adult Schwann cells predominantly express ionotropic glutaminergic receptors (N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isooxazolepropionic acid (AMPA), and kainate) as well as alpha1-, alpha2-, and beta-adrenoreceptors. We conclude that Schwann cells derived from adult guinea pigs express a variety of neuroligand receptors when established in culture and are particularly rich in glutamate receptors. This probably reflects a de-differentiated state important to development and regeneration.

Adenosine Triphosphate↗

PubMed1997

Characterization of a high copy number amplification at 6q24 in pancreatic cancer identifies c-myb as a candidate oncogene.

In a recent study designed to identify chromosomal aberrations in pancreatic cancer tissues using comparative genomic hybridization, a high copy number amplification on 6q was detected. To identify the most likely candidate oncogene, the extension of the amplification in pancreatic cancer tissues and cell lines was determined by Southern blot analysis. Exon trapping was performed with DNA from a yeast artificial chromosome clone containing the complete minimally amplified region. Only fragments from two genes, namely, the c-myb oncogene and a novel gene, were shown to be amplified. The c-myb proto-oncogene was amplified in 10% of the pancreatic carcinoma tissues and in the pancreatic cancer cell line PC2. Interestingly, the c-myb oncogene was overexpressed not only in the amplified samples but also in the majority of the examined pancreatic cancer tissues and cell lines, suggesting that amplification is only one of the mechanisms leading to overexpression. In contrast, the novel gene, which was called human eRF3b (eukaryotic release factor 3b), seems to be only coamplified with c-myb. Genetic alterations of c-myb were mainly found in advanced tumors, indicating a possible correlation to tumor progression and aggressive tumor phenotypes.

Adenocarcinoma↗

PubMed1997

Immune cell infiltration and growth-associated protein 43 expression correlate with pain in chronic pancreatitis.

BACKGROUND & AIMS: Changes in innervation pattern and neuropeptide content have been shown in chronic pancreatitis (CP), including increased neuronal expression of growth-associated protein 43 (GAP-43). We used GAP-43 as an established marker of neuronal plasticity and correlated histological findings with pain scores of patients with CP. METHODS: In tissue samples from 29 patients with CP, the parenchyma-fibrosis ratio, degree of perineural immune cell infiltration, and neuronal GAP-43 immunoreactivity were determined by digitized morphometry and correlated with individual pain scores. RESULTS: In CP, GAP-43 was significantly increased in pancreatic nerve fibers and intrinsic neurons. GAP-43 expression correlated with individual pain scores. The infiltration of pancreatic nerves by immune cells was significantly correlated with the intensity of pain. Pain scores correlated neither with the degree of pancreatic fibrosis nor with the duration of the disease. CONCLUSIONS: The results suggest that infiltration of pancreatic nerves by immune cells and neuronal plasticity are pathogenic factors for the generation of pain, whereas the degree of pancreatic fibrosis has no major impact on pain in CP.

Adolescent↗

PubMed1997

Immunohistochemical detection of human skin nerve fibers.

The autonomic nervous system is involved in different functions such as transduction of afferent sensory inputs, trophic actions, modulation of immunologic events and thermoregulation. In the present investigation, we studied the pattern of human autonomic skin innervation with special reference to its relation to blood vessels, hair follicles, sweat glands and sensory receptors. For the first time, two clinically important areas have been compared: the skin of the forearm and of the face. Using indirect immunohistochemistry, we analyzed the distribution of calretinin (CR), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP), neurokinin A (NKA), vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS), tyrosine hydroxylase (TH), histamine, serotonin, enkephalin, and, enzyme histochemically, NADPH-diaphorase (NADPH-d). In the epidermis, we found nerve fibers containing SP, NKA and CGRP. In the dermis, SP-, CR-, VIP-, CGRP- and NKA-positive nerve fibers were detected. Particularly the large nerve fibers contained CR. VIP-positive fibers occurred especially around hair follicles and sweat glands. CGRP-positive nerve fibers were located close to the epidermal basal membrane, in the wall of blood vessels, and to a lesser extent around hair follicles. Immunoreactivity for SP and NKA in the dermis was observed predominantly in the papillary layer near the epidermal basal membrane. All neuropeptides tested in this study were also detected in the nerve fibers of the subcutis. Most of them were CGRP- and VIP-positive. They occurred in association with sweat glands and large arteries. NPY-positive nerve fibers are predominant in the wall of arteries, arterioles and veins. Nerve fibers containing NKA and SP were less common and identified only in the walls of large arteries in deeper dermal layers. In double-staining experiments, the NADPH-d reaction and reactivity to tubulin revealed a partial co-localization in nerve fibers, blood vessel walls, around glands and ganglionic cells. VIP-positive fibers were more common in the face skin than in the forearm. However, in forearm we detected more NPY-, CGRP-, NKA- and SP-positive nerve fibers than in face skin. These findings are important for future studies on skin disorders, such as sensory neuropathies, inflammatory reactions or allergic responses of human skin.

Blood Vessels↗

PubMed1997

Peripheral nerve regeneration through nerve guides seeded with adult Schwann cells.

This study tested the usefulness of Schwann cells in the repair of a severed nerve with a biosynthetic bridge or guide. Reinforced collagen nerve guides were used to bridge an 18 mm gap in the sciatic nerve of 21 young adult rats. The animals were divided into three groups and the guides were filled with: (i) more than 0.5 x 10(6) cultured syngeneic adult Schwann cells (group L, n = 12); (ii) less than 0.5 x 10(6) Schwann cells (Group S, n = 6); and (iii) phosphate buffered saline (control, n = 3). Schwann cells were pre-labelled with Hoechst dye. Regeneration was assessed functionally and histologically at 1, 2, 3 and 6 + months after surgery. Group L animals showed numerous regenerated axons surrounded by implanted Schwann cells within the first month. The total number of myelinated fibers (12.5 x 10(3)) remained above normal unoperated values (7 x 10(3)) in long-term animals. Regenerated axons were found in Group S in the third month, but no Hoechst labelled cells were found. The number of myelinated fibers (3.9 x 10(3)) remained below normal values in long-term animals. Control guides failed to support axonal regeneration. Functional recovery was evident at week 20 (Group L) and week 30 (Group S) after surgery, with no difference in function between the two groups by the end of the study. Supplementing guides with Schwann cells enhances regeneration of peripheral axons over a distance normally prohibitive. This effect is greatest in the early stages of regeneration (1-3 months) and is dependent on the number of cells implanted.

Animals↗

PubMed1996

Cloning of the VASP (vasodilator-stimulated phosphoprotein) genes in human and mouse: structure, sequence, and chromosomal localization.

The genes encoding the vasodilator-stimulated phosphoprotein (VASP) in human and mouse were isolated, and major parts were sequenced. In both species the gene is composed of 13 exons with conserved exon-intron positions. The mouse VASP cDNA sequence was deduced from the genomic sequence. The predicted amino acid sequence is 89% identical to the human protein. The high nucleotide sequence homology extends not only over the coding regions but also into the 3'-UTRs, indicating a possible function in mRNA targeting or regulation of translation. Prominent 5' CpG islands including multiple SP1 sites indicate a housekeeping function of VASP. Using cosmid DNA as a probe for fluorescence in situ hybridization, the human VASP gene was assigned to chromosome 19q13.2-q13.3, an extended region with homology to mouse chromosome 7. A sequence overlap of the VASP 5'-region with the telomeric end of a cosmid contig physically links the VASP gene with ERCC1. VASP is located about 92 kb distal to ERCC1 and about 300 kb proximal to the myotonic dystrophy protein kinase gene.

Amino Acid Sequence↗

PubMed1996

Human high affinity, Na(+)-dependent L-glutamate/L-aspartate transporter GLAST-1 (EAAT-1): gene structure and localization to chromosome 5p11-p12.

The gene of the human L-glutamate transporter hGLAST-1 (EAAT-1) has been isolated and characterized. The 1626 bp cDNA open reading frame (542 aa) is distributed over ten exons and at least 85 kb on chromosome 5p11-p12. The gene is unrelated to any other previously described neurotransmitter transporter gene family, but its exon/intron structure corresponds largely to that of the Na(+)-dependent neutral amino acid transporter ASCT-1. GLAST-1, ASCT-1 and the glutamate transporters GLT-1 and EAAC-1 have strongly similar amino acid sequences. The L-glutamate transporter gene structures might help to understand the correlation of L-glutamate reuptake in neurodegenerative disorders.

Amino Acid Sequence↗