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T Herzinger

Publications and source records attributed to T Herzinger.

14 recordsLinked to original sources
PubMed2006

Photodynamic therapy of genital condylomata in men.

Current treatments for genital condylomata are not completely satisfactory, as they fail to clear lesions in a proportion of patients, and relapses after successful treatment are frequently seen. Photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA) has been suggested as a novel treatment option. We performed a small open study using topical 5-ALA and red light (630 nm) in nine men with genital condylomata and a history of at least one previous unsuccessful conventional treatment. Complete cure was achieved in three patients, one of whom experienced a relapse after 3 weeks. Three patients showed partial responses, and three showed no response. Based on the currently available evidence, PDT is a viable treatment option for selected cases that fail to respond to other therapies.

Administration, Topical↗
PubMed2005

Treatment of small plaque parapsoriasis with narrow-band (311 nm) ultraviolet B: a retrospective study.

Narrow band (311 nm) ultraviolet B (NB-UVB) has been shown to be a safe and effective treatment for psoriasis and other inflammatory skin diseases. We have therefore employed NB-UVB in the treatment of small plaque parapsoriasis (SPP) since 1996. All patients (16/16) responded with complete remission of the disease after a mean number of 32.8 exposures and a mean total dose of 35.4 J/cm2. Unwanted side-effects were rare (3.3%) and always mild. Relapse of the disease occurred after an average of 29 weeks in those patients who came for follow-up visits. Therefore, NB-UVB is an effective, comparably safe and convenient alternative to psoralen and ultraviolet A therapy or other treatment modalities in the suppression of SPP.

Adult↗
PubMed2002

A hoarse voice.

Explore the source record for details and available documents.

Dermatomyositis↗
PubMed2000

The sign of Leser-Trélat: a paraneoplastic cutaneous syndrome that facilitates early diagnosis of occult cancer.

The sign of Leser-Trélat has been described as a rare cutaneous marker of internal malignancy. We report a patient presenting with the sign of Leser-Trélat, in whom a limited diagnostic workup for an associated malignancy lead to the early diagnosis of asymptomatic renal cell carcinoma and curative tumor nephrectomy. A review on this and other cutaneous paraneoplastic syndromes is given. Since they may be the only presenting sign of an occult cancer, patients with these syndromes should undergo a diagnostic screening program for malignant disease.

Aged↗
PubMed1998

Cyclin D3 is rate-limiting for the G1/S phase transition in fibroblasts.

D-type cyclins are induced in response to mitogens and are believed to control progression through the G1 phase of the cell cycle by activating their corresponding kinase partners (cyclin-dependent kinases). To investigate the function of individual D-type cyclins we have constructed rat fibroblast lines that allow controllable overexpression of a human cyclin D3 cDNA. Overexpression of cyclin D3 led to accelerated passage through G1 in actively proliferating cells with no effect on the overall population doubling time. In cells re-entering the division cycle from a quiescent state, cyclin D3 caused an even more dramatic advancement of S phase entry. Accelerated progression through G0/G1-to-S correlated with premature phosphorylation of the pRb tumor suppressor protein and its relatives, p107 and p130. We conclude that cyclin D3 can act as a rate-limiting G1 cyclin and that this effect involves, in part, the premature phosphorylation of critical substrates.

Animals↗
PubMed1997

Cyclin E-induced S phase without activation of the pRb/E2F pathway.

In cells of higher eukaryotes, cyclin D-dependent kinases Cdk4 and Cdk6 and, possibly, cyclin E-dependent Cdk2 positively regulate the G1- to S-phase transition, by phosphorylating the retinoblastoma protein (pRb), thereby releasing E2F transcription factors that control S-phase genes. Here we performed microinjection and transfection experiments using rat R12 fibroblasts, their derivatives conditionally overexpressing cyclins D1 or E, and human U-2-OS cells, to explore the action of G1 cyclins and the relationship of E2F and cyclin E in S-phase induction. We demonstrate that ectopic expression of cyclin E, but not cyclin D1, can override G1 arrest imposed by either the p16INK4a Cdk inhibitor specific for Cdk4 and Cdk6 or a novel phosphorylation-deficient mutant pRb. Several complementary approaches to assess E2F activation, including quantitative reporter assays in live cells, showed that the cyclin E-induced S phase and completion of the cell division cycle can occur in the absence of E2F-mediated transactivation. Together with the ability of cyclin E to overcome a G1 block induced by expression of dominant-negative mutant DP-1, a heterodimeric partner of E2Fs, these results provide evidence for a cyclin E-controlled S phase-promoting event in somatic cells downstream of or parallel to phosphorylation of pRb and independent of E2F activation. They furthermore indicate that a lack of E2F-mediated transactivation can be compensated by hyperactivation of this cyclin E-controlled event.

Animals↗
PubMed1996

Reactive perforating collagenosis--transepidermal elimination of type IV collagen.

Reactive perforating collagenosis (RPC) is a rare skin disorder characterized by reddish papules with a central keratotic plug which appear mainly on the extensor aspects of the limbs. An idiopathic or classical variant has been delineated from an acquired one which occurs in diabetes mellitus and renal failure. Histopathological examination of the lesions shows transepidermal elimination of abnormally staining bundles of collagen. To clarify the origin of this collagenous material we performed an immunohistochemical study including biopsies of two patients with RPC, one classical and one acquired. Staining reactivity to antibodies against type IV collagen was observed, thus providing evidence that the collagen eliminated in RPC may be derived from the basement membrane zone.

Adult↗
PubMed1995

Ultraviolet B irradiation-induced G2 cell cycle arrest in human keratinocytes by inhibitory phosphorylation of the cdc2 cell cycle kinase.

In response to genotoxic stress, cell cycle progression can be arrested at certain checkpoints which serve to maintain genomic integrity. We have investigated the mechanism of ultraviolet B (UVB) irradiation-induced cell cycle arrest in normal human keratinocytes and in the HaCaT keratinocyte cell line which carries mutant p53 tumour suppressor protein. While only normal keratinocytes showed a delay in G1 following sublethal UVB irradiation both cell types exhibited prolonged G2 arrest attributable to rapid inhibition of cyclin B-associated cdc2 kinase activity. This inhibition coincided with increased tyrosine phosphorylation of cdc2 and was reversed by the cdc25C phosphatase in vitro. The data indicate that UVB-induced G2 arrest in mammalian cells is mediated by inhibitory tyrosine phosphorylation of cdc2 and acts as a defense mechanism against DNA damage irrespective of the cells' p53 status.

CDC2 Protein Kinase↗
PubMed1995

A complex between E2F and the pRb-related protein p130 is specifically targeted by the simian virus 40 large T antigen during cell transformation.

The p130 protein is a recently cloned member of the retinoblastoma protein family. We show here that transformation of NIH3T3-L1 fibroblasts (L1 cells) by the simian virus 40 large T antigen (LTAg) depends on the disruption of DNA binding complexes between transcription factor E2F and p130. LTAg binds to the pocket region of p130 in vivo and disrupts the E2F-p130 complexes. E2F-p130 complexes are present only in quiescent L1 cells and disappear at the G1/S phase boundary concomitantly to induction of DNA synthesis and expression of the E2F-regulated cdc2 gene. p130 is a substrate of cyclin-dependent kinase 2 (Cdk2) in vitro and associates with a Cdk in vivo which is activated upon serum stimulation in late G1. Overexpression of p130 inhibits cdc2 promoter activity and entry of quiescent L1 cells into S phase. The results demonstrate that p130 is negative regulator of cell cycle progression which is specifically targeted by LTAg during cell transformation.

3T3 Cells↗
PubMed1995

The pRb-related protein p130 is a possible effector of transforming growth factor beta 1 induced cell cycle arrest in keratinocytes.

Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit epithelial cell growth by inducing a G1 cell cycle arrest. We have studied the effect of TGF-beta 1 on protein binding to a transcription factor E2F consensus element in extracts from early passage human keratinocytes (HFKs) and a permanent human keratinocyte cell line (HaCaT). Treatment of these cells with TGF-beta 1 resulted in the formation of a DNA binding complex between the pRb-related protein p130 and E2F. Formation of the E2F-p130 complex correlated with inhibition of cell cycle progression in G1 and suppression of the E2F-regulated cdc2 gene. While p130 mRNA and protein levels were not influenced by TGF-beta 1, the activity of cyclin-dependent kinase 2 (Cdk2) towards p130 in vitro was inhibited. The results identify p130 as a downstream target of TGF-beta 1 and a possible mediator of the G1 cell cycle arrest.

CDC2 Protein Kinase↗
PubMed1995

Assessment of cutaneous and ocular irritancy: a decade of research on alternatives to animal experimentation.

Over the past decade increasing societal and scientific pressure has promoted the development of alternatives to local tolerance testing in laboratory animals. The use of isolated organs, fertilized hen's eggs, and cell culture systems has been proposed as well as the study of a toxicant's biochemical effects and structure-activity relationships. This paper critically reviews the current status of these approaches and discusses the preliminaries for the establishment of alternative methods in the process of safety assessment.

Animal Testing Alternatives↗
PubMed1994

Discrimination of the irritancy potential of surfactants in vitro by two cytotoxicity assays using normal human keratinocytes, HaCaT cells and 3T3 mouse fibroblasts: correlation with in vivo data from a soap chamber assay.

Cell cultures have been proposed as a promising model for local tolerance testing. This study evaluated the cytotoxic effects of surfactants on early passage normal human keratinocytes, transformed human keratinocytes (HaCaT cells) and Swiss 3T3 embryonic mouse fibroblasts. Cell membrane integrity, as assessed by the release of the vital dye neutral red, and cell proliferation, as assessed by measurement of the total protein content, were both affected in a dose-dependent manner in response to surfactant exposure. There was a close correlation between the dose-response characteristics for the three cell types. Two surfactants exhibited differential effects on membrane integrity and proliferation, and thus no significant correlation was found between the two endpoints. The irritation potential of the surfactants to human forearm skin in vivo was assessed in a soap chamber test using transepidermal water loss and skin redness as quantitative endpoints. A comparison between the responses in vivo and in vitro yielded the highest correlation for the neutral red release test on normal keratinocytes. The total protein test did not significantly correlate with the soap chamber assay for keratinocytes and HaCaT cells. These results suggest that cultured normal human keratinocytes may be predictive for the irritancy of various surfactants in man. Definite judgement, however, has still to be based on confirmation in human volunteers of larger groups of compounds with diverse physico-chemical properties.

3T3 Cells↗
PubMed1993

Transcriptional and posttranscriptional regulation of human androgen receptor expression by androgen.

Autoregulation is a control mechanism common to several proteins of the steroid/thyroid hormone receptor superfamily. In this work, the effect of androgens and antiandrogens on the expression of the human androgen receptor (hAR) in prostate and breast cancer cell lines was studied. Northern blot analysis revealed a decrease in hAR steady state RNA levels in LNCaP cells by 3.3 nM of the synthetic androgen mibolerone. Maximal down-regulation of hAR RNA to 30% of control levels occurred 48 h after hormone addition. T47D breast cancer cells showed a similar effect with mibolerone, while hAR expression in normal skin fibroblasts did not respond to androgen treatment. As shown by nuclease S1 analysis, hAR transcripts initiate at three principal start sites, all of which are equally sensitive to androgen. Steroidal as well as nonsteroidal antiandrogens were capable of partially antagonizing androgen-mediated hAR RNA down-regulation in LNCaP and T47D cells, while not exerting a significant effect when administered alone. While hAR RNA stability was increased by hormone, nuclear run-on analysis revealed a 4-fold reduction of hAR gene transcription 96 h after androgen treatment. Although decreased hAR RNA levels did not coincide with a parallel decrease in AR protein levels, analysis of androgen-inducible reporter constructs demonstrated that prolonged androgen administration to cells results in a progressively impaired sensitivity of the intracellular androgen response mechanism. These results show that prolonged androgen exposure leads, besides its effect on hAR RNA levels, to functional inactivation of the AR. Thus, in vivo, posttranslational control of AR activity appears to be a novel mechanism of negative autoregulation of androgen effects on gene expression.

Androgens↗