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P Kind

Publications and source records attributed to P Kind.

At least 73 records · Page 4Linked to original sources
PubMed1996

Valuing health states: a comparison of methods.

In eliciting health state valuations, two widely used methods are the standard gamble (SG) and the time trade off (TTO). Both methods make assumptions about individual preferences that are too restrictive to allow them to act as perfect proxies for utility. Therefore, a choice between them might instead be made on empirical grounds. This paper reports on a study which compared a "props" (using specifically-designed boards) and a "no props" (using self-completion booklets) variant of each method. The results suggested that both non props variants might be susceptable to framing effects and that TTP props outperformed SG props.

Adolescent↗
PubMed1996

Inconsistency and health state valuations.

The comparison of scaling methods used to value health states sometimes rests upon an analysis of aggregate scores. This analysis is usually undertaken once 'inconsistent' respondents have been excluded from the data. However, it is important to be able to judge the extent to which respondents as a whole are logically consistent when assigning values to health states. The degree of inconsistency will depend on how the health states are described, how the questionnaire is administered and who the respondents are. This paper analyses the inconsistency rates from two studies in which valuations for EuroQol health states were elicited using the visual analogue scale (VAS) method. The studies differed in design and incorporated several different variants of the standard EuroQol questionnaire, thus providing an opportunity to examine the relative importance of the different factors that were thought to affect inconsistency rates. Our general conclusions are that inconsistency rates are higher for interviewer-based than for postal surveys, possibly due to response bias, and that inconsistency rates are positively related to age and negatively related to educational attainment.

Activities of Daily Living↗
PubMed1996

Strong and prolonged induction of c-jun and c-fos proto-oncogenes by photodynamic therapy.

Photodynamic therapy (PDT) is currently under investigation in phase II and III clinical studies for the treatment of tumours in superficial localisations. Thus far, the underlying mechanisms of PDT regarding cellular responses and gene regulation are poorly understood. Photochemically generated singlet oxygen (1O2) is mainly responsible for cytotoxicity induced by PDT. If targeted cells are not disintegrated, photo-oxidative stress leads to transcription and translation of various stress response and cytokine genes. Tumour necrosis factor (TNF) alpha, interleukin (IL) 1 and IL-6 are strongly induced by photodynamic treatment, supporting inflammatory action and immunological anti-tumour responses. To investigate the first steps of gene activation, this study focused on the proto-oncogenes c-jun and c-fos, both coding for the transcription factor activator protein 1 (AP-1), which was found to mediate IL-6 gene expression. We here determine the effects of photodynamic treatment on transcriptional regulation and DNA binding of transcription factor AP-1 in order to understand the modulation of subsequent regulatory steps. Photodynamic treatment of epithelial HeLa cells was performed by incubation with Photofrin and illumination with 630 nm laser light in vitro. Expression of the c-jun and c-fos genes was determined by way of Northern blot analysis, and DNA-binding activity of the transcription factor AP-1 was evaluated by electrophoretic mobility shift assay (EMSA). Photofrin-mediated photosensitisation of HeLa cells resulted in a rapid and dose-dependent induction of both genes but preferential expression of c-jun. Compared with the transient expression of c-jun and c-fos by phorbol ester stimulation, photodynamic treatment led to a prolonged activation pattern of both immediate early genes. Furthermore, mRNA stability studies revealed an increased half-life of c-jun and c-fos transcripts resulting from photosensitisation. Although mRNA accumulation after PDT was stronger and more prolonged compared with phorbol ester stimulation, with regard to AP-1 DNA-binding activity, phorbol ester was more efficient. Surprisingly, in addition to the activation of AP-1 DNA-binding via PDT, photodynamic treatment can decrease AP-1 DNA-binding of other strong inducers, such as the protein kinase C-mediated pathway of phorbol esters and the antioxidant pyrrolidine dithiocarbamate (PDTC). This study demonstrates a strong induction of c-jun and c-fos expression by PDT, with prolonged kinetics and mRNA stabilisation as compared with activation by phorbol esters. Interestingly, this observation is not coincident with an overinduction of AP-1 DNA-binding, hence suggesting that post-translational modifications are dominant regulatory mechanisms after PDT that tightly control AP-1 activity in the nucleus thus limiting the risk of deregulated oncogene expression.

Antioxidants↗
PubMed1996

Protein kinase C activation is involved in ultraviolet B irradiation-induced endothelial cell ICAM-1 up-regulation and lymphocyte-endothelium interaction in vitro.

Lymphocyte-endothelium interactions are pivotal steps in mediating inflammatory responses. The authors have analysed the influence of ultraviolet B (UVB) irradiation on intercellular adhesion molecule (ICAM)-1 expression on cells of the human microvascular endothelial cell line (HMEC)-1 and the intracellular signalling pathways involved. Flow cytometry revealed dose-dependent ICAM-1 up-regulation with maximum induced expression 24h after sublethal UVB irradiation of 10 mJ/cm2. While anti-tumour necrosis factor (TNF)-alpha antibodies or recombinant human interleukin (IL)-10 did not influence this response, anti-interferon (IFN)-gamma antibodies blocked the UVB-induced ICAM-1 up-regulation. Significant induction of intracellular/membrane-bound IFN-gamma was measured as early as 6 h post-UVB. Since previous work has shown a differential role of protein kinase C (PKC) in cytokine induced ICAM-1 expression, the effect of a selective bisindolylmaleimide-derived PKC-inhibitor (GF109203X) was studied. Ultraviolet B-induced ICAM-1 up-regulation was effectively blocked by the PKC-inhibitor, whereas a PKA-inhibitor was ineffective. Moreover, immunofluorescence analysis showed a radiation-induced membrane translocation of PKC-alpha, indicative of enzyme activation, in HMEC-1 cells already 30 min post-UVB. The functional relevance of the UVB-induced ICAM-1 expression and involvement of PKC in this process was demonstrated in an adhesion assay with peripheral blood mononuclear cells. In conclusion, UVB-induced ICAM-1 expression on human endothelial cells involves PKC-dependent pathways and can be prevented by a PKC-inhibitor. The use of PKC-inhibitors as additive modulators in immune reactions may bear clinical potential. The mechanisms of IFN-gamma induction in endothelial cells by UVB deserve further investigation.

Cell Adhesion↗
PubMed1996

Diffuse sebaceous gland hyperplasia. A case report and an immunohistochemical study with cytokeratins.

We report a 43-year-old woman with sebaceous gland hyperplasia that occurred in a diffuse pattern of aggregated papular lesions involving her entire face, neck, and upper chest. Comedones, pustules, and inflammatory papules were absent. The eruption was accompanied by marked seborrhea. Histopathological examination showed enlargement of sebaceous acini, an increased number of immature sebocytes in foci, and a dilated follicular infundibulum. Immunohistochemical investigation showed cytokeratin 14 (CK 14) expression in the keratinocytes of the infundibulum, the isthmus, and sebaceous duct and in the mature and immature sebocytes; CK 17 expression in the keratinocytes of the sebaceous duct; CK 1 expression in the keratinocytes of the infundibulum; and an enhanced expression of the proliferation cell antigen Ki-67 (MiB1) in the immature sebocytes. With CK 18 and CK 19, no staining was observed. Oral therapy with isotretinoin (13-cis-retinoic acid) resulted in remarkable improvement in < or = 3 months. Histopathological and immunohistochemical examination after therapy showed markedly reduced sebaceous glands, a decrease in the staining of MiB1-positive immature sebocytes, and enhanced expression of CK 19 in immature sebocytes and sebaceous duct cells. Diffuse sebaceous gland hyperplasia is a rare variant of seboglandular proliferative disorders that is distinct from the well-known circumscribed type.

Administration, Oral↗
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↗
PubMed1996

T-cell-rich B-cell lymphoma presenting in skin. A clinicopathologic analysis of six cases.

We reviewed our experience with six T-cell-rich B-cell lymphomas (TRBL) presenting in skin. Immunohistochemical studies were performed on all biopsies. The lymphoid population consisted mainly of CD3 and/or UCHL-1 (CD45RO) positive T cells. 5 to 15% of the lymphoid cells stained for the B-cell marker L26 (CD20). Monoclonality of the B-cell component was demonstrated in all cases, utilizing either light chain restriction (5 cases) or clonal immunoglobulin heavy chain gene rearrangement by polymerase chain reaction (PCR) (2 cases). One case was confirmed to be monoclonal by both techniques. Additionally, no clonal rearrangements of the T-cell receptor gamma gene were observed. There was considerable morphological variety in these cases. In H&E stained sections, the differential diagnosis included pseudolymphoma, peripheral T-cell lymphoma, Hodgkin's disease, Lennert's lymphoma and a MALT lymphoma. A significant component of monoclonal plasma cells was present in 3 of 6 cases, suggesting a possible origin from cutaneous immunocytoma. In fact, one of our cases was a biphasic lymphoma displaying TRBL with a small focus of immunocytoma. We conclude that immunophenotypic analysis is necessary for the diagnosis of TRBL. Pathologists should be aware of this type of cutaneous B-cell lymphoma to avoid misinterpretation as a pseudolymphoma.

Adult↗
PubMed1996

The hyperkeratotic variant of porokeratosis Mibelli is a distinct entity: clinical and ultrastructural evidence.

An isolated case with the hyperkeratotic variant of porokeratosis Mibelli (PM) is reported. The 62-year-old woman developed multiple brown macules with well demarcated large keratotic nodules on both legs. Histopathological studies revealed the presence of a cornoid lamella characteristic of porokeratosis. Ultrastructural investigations revealed dyskeratotic as well as edematous, swollen keratinocytes; autophagocytotic vacuoles were visible. The clinical and ultrastructural peculiarities of the hyperkeratotic variant of PM suggest the possibility of a separate entity.

Administration, Topical↗
PubMed1996

Cutaneous manifestations of congenital afibrinogenaemia.

Skin problems from coagulation disorders have rarely been described in the dermatological literature. Here we report a patient with a complete congenital absence of fibrinogen which led to leg ulceration, necrosis of the toes and a life-threatening haemorrhage following skin biopsy. This patient shows that leg ulcers may have a complex aetiology and can reflect serious underlying disease.

Adult↗
PubMed1996

Preferences for schizophrenia-related health states: a comparison of patients, caregivers and psychiatrists.

Health state preferences are important for evaluating the outcomes of medical treatment. This study examined preferences of patients for schizophrenia-related health states and compares patient preferences with those of caregivers and psychiatrists. Health-state descriptions were developed for five different outcomes likely to be experienced by schizophrenic patients. Forty-nine schizophrenic patients and their primary caregiver assigned preferences to the hypothetical states and the patient's current state using categorical rating scales and paired comparisons; physicians rated the states using the standard gamble and categorical rating scale. Mean standard gamble utilities for the patient's current health were 0.75, and ranged from 0.56 for the inpatient state to 0.83 for excellent function, outpatient. Mean categorical rating scale preferences for the patient's current health state were 0.67 for patients, 0.66 for caregivers and 0.66 for clinicians. Patient preferences were comparable with clinician and caregiver preferences for hypothetical health states. Patient preferences were correlated with clinician and caregiver preferences for current health. It was concluded that schizophrenic patients are able to complete categorical rating scales and paired comparisons, and patient preferences are associated with clinician and caregiver preferences.

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

Photodynamic therapy induces expression of interleukin 6 by activation of AP-1 but not NF-kappa B DNA binding.

Inducibility and regulation of the pleiotropic cytokine interleukin 6 (IL-6) upon photodynamic therapy (PDT) was studied in the epithelial cell line HeLa. Photofrin-mediated photosensitization resulted in a rapid and dose-dependent induction of IL-6 mRNA production. Maximal levels were reached after 4 h and had decreased to baseline levels after 24 h. This photochemical induction of IL-6 transcription was followed by a strong secretion of IL-6 protein. In comparison to stimulation by 12-O-tetradecanoylphorbol-13-acetate, the kinetics of IL-6 mRNA and protein synthesis after PDT were delayed, although the maximal amounts of secreted IL-6 protein were comparable. As compared to UV irradiation, on the other hand, PDT-induced IL-6 protein levels were 2- to 10-fold higher and were detectable 4 h earlier. Several potentially relevant regulatory DNA elements of the IL-6 promoter were analyzed by gel retardation assays for PDT-induced protein binding. Interestingly, increased AP-1 DNA binding was detected only at the distal AP-1-specific motif and not at the proximal site, differing in 1 bp. Binding of c-Fos-containing AP-1 heterodimers to the specific motif was up-regulated 30 min after PDT, reaching maximal activity at 4 h. This PDT-induced AP-1 activation was independent from protein kinase C activity. Photosensitization did not induce increased binding at the well-characterized NF-kappa B element, nor at the multiple cytokine- and second messenger-responsive element of the IL-6 promoter. By analyzing the molecular mechanisms of IL-6 up-regulation upon PDT, we provide evidence for regulatory differences compared to UV light, ionizing irradiation, or stimulation by phorbol ester. Furthermore, this study suggests that the "proinflammatory" cytokine IL-6 might be involved in the inflammatory reaction and subsequent immunological antitumor responses.

Base Sequence↗
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

[Trichoblastoma. A tumor with follicular differentiation].

The purpose of this article is to inform about neoplasms with follicular differentiation, particularly trichoblastoma. In 1970 Headington divided neoplasms of the hair germ (trichogenic tumours) into four groups: purely epithelial without inductive changes (trichoblastomas), mixed epithelial-mesenchymal with inductive changes (trichoblastic fibromas), mixed epithelial-mesenchymal with inductive changes and advanced hair follicle formations (trichogenic trichoblastomas), and predominantly mesenchymal with an abortive dermal hair papilla (trichogenic myxoma). Meanwhile a new classification of neoplasms with follicular differentiation has been presented, according to which every neoplasm with follicular differentiation, benign structure (symmetrical, circumscribed, with vertical growth), and predominance of follicular germinative cells is called a trichoblastoma. Whether this neoplasm is malignant and if so to what degree is under discussion. This classification is gaining in acceptance among histopathologists but has not been accepted in the field of clinical dermatology.

Basal Cell Carcinoma↗
PubMed1995

[Hamartoma of the sebaceous follicle. An immunohistologic analysis with cytokeratins].

A 62-year-old man presented with a nodule 2 cm in diameter on his left cheek, which he had had since childhood. Histological examination showed a circumscribed dermal nodule composed of sebaceous lobules attached to sebaceous ducts and to an infundibular cyst-like structure connected to the epidermis. The wall was lined with squamous epithelium with a stratum granulosum. This structure was reminiscent of a sebaceous follicle. In addition, a melanocytic naevus of the compound type was found. Immunohistological investigations of the tumour with various cytokeratins revealed a pattern of expression characteristic for the mature sebaceous follicle.

Biomarkers, Tumor↗