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Biomedical subjects

P Wolf

Publications and source records attributed to P Wolf.

At least 73 records · Page 4Linked to original sources

Accidental bullous phototoxic reactions to bergamot aromatherapy oil.

Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium ssp bergamia) that has a pleasant, refreshing scent; until a few years ago it had been widely used as an ingredient in cosmetics but was restricted or banned in most countries because of certain adverse effects. More recently, oil of bergamot preparations have been gaining renewed popularity in aromatherapy. Oil of bergamot possesses photosensitive and melanogenic properties because of the presence of furocoumarins, primarily bergapten (5-methoxypsoralen [5-MOP]). However, 5-MOP is also potentially phototoxic and photomutagenic. Despite its increasing application, there are only a few recent reports of phototoxic reactions to bergamot aromatherapy oil. We describe two patients with localized and disseminated bullous phototoxic skin reactions developing within 48 to 72 hours after exposure to bergamot aromatherapy oil and subsequent ultraviolet exposure. One patient (case 2) had no history of direct contact with aromatherapy oil but developed bullous skin lesions after exposure to aerosolized (evaporated) aromatherapy oil in a sauna and subsequent UVA radiation in a tanning salon. This report highlights the potential health hazard related to the increasing use of psoralen-containing aromatherapy oils.

Adult↗

Epidermal growth factor-like ligands and erbB genes in the peri-implantation rabbit uterus and blastocyst.

Molecular cloning of the partial cDNA coding sequences of the four erbB receptors and the epidermal growth factor (EGF)-like ligands EGF, transforming growth factor alpha (TGF), and heparin-binding EGF (HB-EGF) has provided the basis for a comprehensive analysis of the spatiotemporal expression pattern of the EGF receptor/ligand system during the peri-implantation period in the rabbit. Employing nonradioactive in situ hybridization and immunolocalization, we observed differential expression of erbB1-erbB3 within the trophectoderm of the blastocyst. ErbB1 was strongly expressed in the cytotrophoblast but was downregulated upon syncytium formation. ErbB3 was a product of both the cyto- and syncytiotrophoblast. Despite the expression of erbB2 mRNA, the trophectoderm was devoid of immunoreactive ErbB2. ErbB4 gene activity was exclusively detected in the trophoblast at midpregnancy. The luminal and glandular epithelium and stroma of the nonpregnant, pseudopregnant, and pregnant rabbit uterus at Day 6 of gestation also expressed ErbB1-ErbB3. In the peri-implantation period, gene activities of erbB1-erbB3 were upregulated upon decidualization. At the site of implantation, uterine luminal epithelial cells apposing the preimplantation blastocyst displayed a distinct membrane immunolocalization of ErbB2, identifying the uterine epithelium as target for EGF, TGFalpha, and HB-EGF derived from both the embryonic trophectoderm and the uterine epithelium. In the luminal epithelium at the antimesometrial uterine site, HB-EGF gene activity was upregulated at the time of blastocyst attachment, but this upregulation was not reflected in an increase in immunoreactive HB-EGF. The detection of tyrosine phosphorylated ErbB2 in the rabbit placenta indicated the presence of a functional ErbB/EGF-like system in the pregnant rabbit uterus. This study provides strong evidence for a role of the ErbB/EGF-like system in embryo/maternal interactions during the peri-implantation period in the rabbit.

Animals↗

Collision of squamous-cell carcinoma with melanoma in situ in a child with xeroderma pigmentosum.

Coexistence (collision) of two different neoplasms in the same lesion has previously been documented by several authors. In this report, we describe a 13-year-old boy with xeroderma pigmentosum presenting with squamous-cell carcinoma and melanoma arising at the same site on the nose. Histopathologically, the melanoma component of the lesion was located mainly eccentrically to the squamous-cell carcinoma component. Immunohistochemical stains confirmed the histopathologic findings. Mutations for p53 assessed using single-strand conformation polymorphism, and sequencing analysis revealed a CC-to-TT transition at codon 159 of the p53 gene in the squamous-cell component but not in the melanoma component. This finding suggests a possible role for UV in the pathogenesis of at least the squamous-cell component of the tumor. To the best of our knowledge, this is the first report of a collision tumor comprising squamous-cell carcinoma and melanoma arising in childhood.

Adolescent↗

High mutation frequency at Ha-ras exons 1-4 in squamous cell carcinomas from PUVA-treated psoriasis patients.

Clinical follow-up studies have revealed that PUVA-treated patients are at increased risk of skin cancer, particularly squamous cell carcinoma (SCC). However, since psoralen and UVA (PUVA) is not only a potent mutagen and carcinogen but also an immunosuppressor, and since other (co)carcinogenic factors often exist in psoriasis patients, the exact causes and mechanisms of PUVA-associated SCC are still not completely understood. In order to fill this gap the tools of molecular epidemiology are being used to study the SCC mutational spectra of p53 and Ha-ras, two of the most commonly mutated genes in human cancers. A previous mutation analysis revealed that SCC in PUVA-treated patients often carried mutated p53 genes and that many of the mutations had the UV fingerprint (i.e. C-->T or CC-->TT transitions at dipyrimidine sites). In the present study DNA-sequencing analysis revealed a total of 18 Ha-ras missense or nonsense mutations at exons 1-4 in 13 of 17 SCC (76%) from 8 of 11 (73%) PUVA-treated psoriasis patients. Six of the 18 mutations (33%) were of UV-fingerprint type (C-->T transitions), five (28%) were at 5'-TpG sites (i.e. potential psoralen-binding sites and thus potentially caused by PUVA) and seven were of other type (39%), including six G:C-->T:A transversions at hotspot codon 12. In addition, in the case of 6 of the 11 subjects (55%) both tumor and normal skin samples contained a T:A-->C:G base change at codon 27 (a 5'-ATT site), a change previously hypothesized to be a possible silent Ha-ras polymorphism at one allele. When we compared the present Ha-ras mutation spectrum with the p53 mutation spectrum from a previous study of the samples, we found that approximately half of the tumors harbored mutations in both Ha-ras and p53. Together, our results indicate that Ha-ras mutations are present in a large proportion of PUVA-associated SCC and that UVB, PUVA and other agents may induce Ha-ras mutations and act together with p53 in the formation of SCC in psoriasis patients.

Base Sequence↗

Charge-process strategies for outpatient prospective payment.

One of the most important strategies for operating successfully under the outpatient prospective payment system is to establish an effective charging process. Achieving control of the process begins with a thorough assessment of chargemaster coding, how charges are structured in the chargemaster, and how hospital departments use the charges. Once problems are identified and corrected, the next step is to develop a system to maintain and monitor both the chargemaster and the charging process. Perhaps the most important component of the monitoring system is to include a mechanism to provide the necessary feedback to departments regarding errors related to the charge process.

Ambulatory Care↗

Comparative phenotype and immunogenicity of freshly isolated and immortalized rat hepatocytes.

Immortalized hepatocytes are an attractive cell source for hepatocyte transplantation and gene transfer. We compared the phenotype and immunogenicity of freshly isolated (FIH) and immortalized (IMH) rat hepatocytes. Effect of culture and proinflammatory cytokines (TNF-alpha, IFN-gamma) was studied on phenotype. FIH were isolated by collagenase digestion. Two SV40 immortalized hepatocyte cell lines were tested (RH1 and P9). Immunophenotyping was performed by FACS analysis using anti-rat-specific antibodies. Immunogenicity was evaluated by a mixed lymphocyte hepatocyte reaction (MLHR). FIH suspension was an almost homogeneous parenchymal cell population with few (1-2%) CD8+ cells. FIH showed a positive staining for ICAM-1 (20-35%) and for Class I (RT1A, 30-60%) but no staining for Class II (RT1B). After 48 h of culture, the already ICAM-1-positive cells were more strongly stained and additionally 3.6% of the cells (possibly endothelial cells) were Class II positive. IMH showed a consistent expression of Class I (93-97%) and ICAM-1 (95-97%) but no expression of Class II. Culture of IMH for 48 h had no effect on Class II expression but increased ICAM-1 expression. Addition of TNF-alpha at 1000 UI/ml to cultures of FIH or IMH increased Class I and ICAM-1 expression whereas IFN-gamma (50 or 1000 UI/ml) had no evident effect. Hepatocyte immunogenicity, assessed in MLHR and appreciated by the stimulation index (SI) test/SI syngeneic control, was similar for IMH (RH1: 2.68+/-0.89; P9: 2.37+/-0.78) and FIH (2.52+/-0.18). In conclusion, despite some quantitative immunophenotypic differences, FIH and IMH induced the same proliferation rate of allogeneic T lymphocytes. Thus, immortalized hepatocytes may constitute an appropriate cellular model to study the prevention of hepatocyte rejection by gene transfer.

Animals↗

Vigabatrin reduces epileptiform activity in brain slices from pharmacoresistant epilepsy patients.

Human neocortical temporal lobe tissue resected for treatment of pharmacoresistant epilepsy was investigated. In slices prepared from this tissue, epileptiform field potentials (EFP) were induced by omission of magnesium from the artificial cerebrospinal fluid (ACSF). The effects of the gamma-aminobutyric acid transaminase inhibitor vigabatrin on EFP were tested. Vigabatrin exerted a dose-dependent reduction of the repetition rate of EFP: after 3 h of administration of vigabatrin in concentrations of 100 and 200 micromol/l, the repetition rate of EFP was reduced to 35% and 18% of the initial values, respectively. This effect was not reversible. In control experiments with neocortical slices from rats, vigabatrin reduced EFP in a comparable range. The results demonstrate a strong antiepileptic effect of vigabatrin on EFP in tissues from pharmacoresistant epilepsy patients.

Adolescent↗

Primary cutaneous follicle center cell lymphoma with follicular growth pattern.

Cutaneous B-cell infiltrates showing a prominent follicular growth pattern with germinal centers are thought by some authors to represent either marginal zone lymphomas with reactive germinal centers or pseudolymphomas. To establish whether a true primary cutaneous follicular lymphoma exists, we studied biopsies from 15 patients with skin lesions characterized histopathologically by the presence of B-cell infiltrates with follicular pattern. Staging investigations, including bone marrow biopsy, were negative in all patients. All were negative for bcl-2 protein expression and did not present the t(14;18). In all biopsy specimens neoplastic follicles showed 1 or more morphologic or immunophenotypic criteria of malignancy (presence of a reduced mantle zone, absence of tingible body macrophages, reduced proliferation rate). In 9 specimens a monoclonal rearrangement of J(H) genes could be detected by polymerase chain reaction analysis. After laser beam microdissection, a band of the same length could be observed in 6 probes from different follicles from the same specimen, indicating the presence of the same monoclonal population of follicle center cells. Follow-up examinations in all patients revealed no evidence of extracutaneous spread (mean follow-up, 48.7 months). Our study demonstrates that primary cutaneous follicular lymphoma represents a distinct entity of the cutaneous B-cell lymphomas. (Blood. 2000;95:3922-3928)

Adult↗

Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia.

Inactivation of the beta4 subunit of the calcium channel in the mouse neurological mutant lethargic results in a complex neurological disorder that includes absence epilepsy and ataxia. To determine the role of the calcium-channel beta4-subunit gene CACNB4 on chromosome 2q22-23 in related human disorders, we screened for mutations in small pedigrees with familial epilepsy and ataxia. The premature-termination mutation R482X was identified in a patient with juvenile myoclonic epilepsy. The R482X protein lacks the 38 C-terminal amino acids containing part of an interaction domain for the alpha1 subunit. The missense mutation C104F was identified both in a German family with generalized epilepsy and praxis-induced seizures and in a French Canadian family with episodic ataxia. These coding mutations were not detected in 255 unaffected control individuals (510 chromosomes), and they may be considered candidate disease mutations. The results of functional tests of the truncated protein R482X in Xenopus laevis oocytes demonstrated a small decrease in the fast time constant for inactivation of the cotransfected alpha1 subunit. Further studies will be required to evaluate the in vivo consequences of these mutations. We also describe eight noncoding single-nucleotide substitutions, two of which are present at polymorphic frequency, and a previously unrecognized first intron of CACNB4 that interrupts exon 1 at codon 21.

Amino Acid Sequence↗

[Squamous epithelial carcinoma in erythema ab igne].

Erythema ab igne (EAI) is a red-brown net-like hyperpigmentation due to repetitive exposure to submaximal heat over a long period of time. This rash is typically seen on the anterior lower legs of people who sit in front of open fireplaces or coal stoves and on the trunk of patients with chronic disorders who seek pain relief by long-term use of hot-water bottles or heating pads. EAI can not only be a diagnostic sign for underlying internal diseases including malignant tumors but can also give rise to cutaneous malignancies. We report on a 75-year-old female patient who developed several thermal keratoses and squamous cell carcinomas at the site of erythema ab igne caused by chronic heat exposure over several years.

Abdominal Neoplasms↗