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Biomedical subjects

Peter Wolf

Publications and source records attributed to Peter Wolf.

48 records · Page 3Linked to original sources
PubMed2003

High frequency of ultraviolet mutations at the INK4a-ARF locus in squamous cell carcinomas from psoralen-plus-ultraviolet-A-treated psoriasis patients.

Squamous cell carcinomas in psoralen-plus-ultraviolet A (PUVA) treated patients frequently exhibit p53 tumor suppressor genes and Ha-ras protooncogenes that are mutated at dipyrimidine sites and carry the ultraviolet fingerprint (i.e., C-to-T or CC-to-TT transitions). To further broaden the knowledge of genetic mutations in PUVA-associated skin cancer, we used DNA sequencing analysis to study the mutational spectrum of the INK4a-ARF locus in 26 squamous cell carcinomas from 11 long-term PUVA-treated psoriasis patients and classified the mutations by origin (ultraviolet, ultraviolet and/or PUVA, or other). Nineteen INK4a-ARF missense/nonsense mutations were found in exons 1alpha, 1beta, and 2 in 11 of 26 squamous cell carcinomas (42%) from seven of 11 patients (64%). Eleven mutations (58%) were of the ultraviolet type; three (16%) were of the ultraviolet and/or PUVA type (i.e., C-to-T transitions at dipyrimidine sites opposite a 5'TpG sequence, a potential psoralen binding site); and five (26%) were of other type. Interestingly, 10 of 11 patients (91%) showed intron polymorphism C500G at the 3' untranslated region of exon 3. These data indicate that (i) INK4a-ARF mutations frequently occur in PUVA-associated squamous cell carcinomas; (ii) ultraviolet B radiation is the major cause of these mutations; and (iii) PUVA itself may play no direct role in development of most INK4a-ARF mutations.

Adult↗
PubMed2003

Immune protection factors of chemical sunscreens measured in the local contact hypersensitivity model in humans.

We conducted a randomized trial designed to calculate human in vivo immune protection factors of two sunscreen preparations in a model of ultraviolet-induced local suppression of the induction of contact hypersensitivity to 2,4-dinitrochlorobenzene. Seventy-five male subjects were exposed in a multistage study to multiples of their individual minimal erythema dose of solar-simulated ultraviolet radiation with or without protection by an ultraviolet B sunscreen (sun protection factor 5.2) or a broad-spectrum ultraviolet A + B sunscreen (sun protection factor 6.2). After 24 h subjects were sensitized with 50 microL of 0.0625% 2,4-dinitrochlorobenzene on a nonirradiated or ultraviolet-irradiated field on the buttock that was unprotected or protected by sunscreen. Three weeks after sensitization the subjects were challenged with varying concentrations of 2,4-dinitrochlorobenzene on their upper inner arm, and the contact hypersensitivity response was determined at 48 and 72 h based on a semiquantitative clinical score, contact hypersensitivity lesion diameters, and dermal skin edema measurement by 20 MHz ultrasound. The 50% immunosuppressive dose ranged from 0.63 to 0.79 minimal erythema dose, depending on the endpoint parameter. Both sunscreens offered significant immunoprotection (p = 0.014-0.002) and their immune protection factor ranged from 4.5 to 5.8 (ultraviolet B sunscreen) and from 7.7 to 11 (ultraviolet A + B sunscreen). The immune protection factor of the ultraviolet B sunscreen was similar to the sun protection factor (5.2), whereas the sunscreen with broad-spectrum ultraviolet A + B protection exhibited better immunoprotective capacity than predicted from the sun protection factor.

Adult↗
PubMed2002

Repeated subinflammatory ultraviolet B irradiation increases substance P and calcitonin gene-related peptide content and augments mustard oil-induced neurogenic inflammation in the skin of rats.

The cutaneous neurosensory system is suggested to be involved in the pathophysiology of pruritus and skin diseases such as psoriasis. We investigated if repeated subinflammatory doses of ultraviolet B (UVB) irradiation similar to those used to treat pruritus or psoriasis would affect the cutaneous neurosensory system. Sprague-Dawley rats were irradiated thrice weekly for 2-4 weeks with subinflammatory doses of UVB. Three days after the last UVB exposure: (i), the skin contents of substance P (SP), calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) were quantified; (ii), the skin nerve fiber density was observed; and (iii), the effect of UVB on mustard oil-induced neurogenic inflammation was determined. UV exposure significantly increased SP and CGRP content and mustard oil-induced neurogenic inflammation in UV-irradiated but not non-irradiated skin; however, it did not affect cutaneous NGF content or overall nerve fiber density. These data suggest that repeated subinflammatory UVB irradiation locally increases the content of cutaneous SP and CGRP by an increase of neuropeptide content of nerve fibers rather than by an increase of overall nerve fiber density.

Animals↗
PubMed2002

Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) at sites typical for Borrelia burgdorferi infection.

BACKGROUND: Cutaneous manifestations of B-cell chronic lymphocytic leukemia (B-CLL) comprise a wide spectrum of clinicopathologic presentations. In some cases, onset of skin lesions is triggered by antigenic stimulation, and specific skin infiltrates at sites of previous herpes simplex or herpes zoster infection have been well documented. Specific skin manifestations of B-CLL can also be observed at sites typical for lymphadenosis benigna cutis (nipple, scrotum, earlobe), a Borrelia burgdorferi-associated cutaneous B-cell pseudolymphoma. METHODS: We studied specific skin manifestations of B-CLL arising at sites typical for B. burgdorferi-induced lymphadenosis benigna cutis, analyzing tissues for presence of B. burgdorferi DNA using the polymerase chain reaction (PCR) technique. Six patients with B-CLL (M : F = 4 : 2; mean age: 67.8) presented with specific skin lesions located on the nipple (four cases) and scrotum (two cases). RESULTS: Clinically there were solitary erythematous plaques or nodules. Histology revealed in all cases a dense, monomorphous infiltrate of small lymphocytes showing an aberrant CD20+/CD43+ phenotype. In all cases monoclonality was demonstrated by PCR analysis of the JH gene rearrangement. PCR analysis showed in four of the six cases the presence of DNA sequences specific for B.burgdorferi. CONCLUSIONS: Our study demonstrates that infection with B. burgdorferi can trigger the development of specific cutaneous infiltrates in patients with B-CLL.

Aged↗
PubMed2002

Pre- rather than co-application of vigabatrin increases the efficacy of tiagabine in hippocampal slices.

PURPOSE: The antiepileptic drug vigabatrin (VGB) increases intracellular availability of the inhibitory transmitter gamma-aminobutyric acid (GABA) by inhibition of GABA-transaminase. A blockade of the GABA uptake is the main mechanism of action of tiagabine (TGB). Based on this, the two antiepileptic drugs (AEDs) can be speculated to act synergistically so that their combined antiepileptic efficacy is supraadditive. METHODS: To test this, experiments were performed on hippocampal slices of guinea-pigs. As an epilepsy model, epileptiform field potentials (EFPs) were induced by omission of Mg2+ from the bath solution and recorded in stratum pyramidale of the CA3 region. VGB (7.5 microM) and TGB (0.75 microM) were added to the superfusate. RESULTS: VGB, given alone, failed to decrease the repetition rate of EFPs. Similarly, TGB applied alone only transiently led to a nonsignificant reduction of the EFP frequency. Combining VGB and TGB, their suppressive efficacy increased, yielding a significant reduction of EFP frequency, which, however, again did not persist. Pretreatment of the preparations with VGB for 2 h, followed by additional application of TGB, or TGB alone, drastically and persistently potentiated the effects. CONCLUSIONS: These results demonstrate that VGB and TGB show favorable pharmacodynamic interactions, provided VGB is allowed to block intracellular GABA degradation before GABA uptake block by TGB.

Animals↗
PubMed2002

Effect of levetiracetam on epileptiform discharges in human neocortical slices.

PURPOSE: The anticonvulsant effects of the novel antiepileptic drug (AED) levetiracetam (LEV) were tested in neocortical slice preparations from 23 patients who underwent surgery for the treatment of refractory epilepsy. METHODS: Slices were used to evaluate the effects of LEV on two different models of epilepsy: low-Mg2+-induced untriggered and bicuculline-evoked stimulus-triggered epileptiform burst discharges and spontaneously appearing rhythmic sharp waves. RESULTS: LEV (0.1-1 mM) did not influence spontaneously appearing rhythmic sharp waves or Mg2+-free aCSF-induced epileptiform field potentials. LEV affected neither the amplitudes or duration nor the repetition rates of burst discharges in these epilepsy models. However, LEV (100-500 microM) significantly suppressed the ictal-like discharges elicited by the gamma-aminobutyric acid subtype A (GABAA)-receptor antagonist bicuculline. A marked reduction of the amplitude and duration of bicuculline-evoked field response in the presence of LEV was observed. CONCLUSIONS: The results indicate the potential for LEV to inhibit epileptiform burst discharges in human neocortical tissue, which is consistent with its effects in animal models of epilepsy. These results also support the seizure reduction observed in clinical trials and support that this may, in part, be related to the ability of LEV to inhibit epileptiform discharges.

Adolescent↗
PubMed2002

The role of nonpharmaceutic conservative interventions in the treatment and secondary prevention of epilepsy.

Nonpharmacologic conservative treatments receive too little attention. Depending on the clinical condition of the patients, they may be used alone or in conjunction with other therapies. Their target is the single seizure rather than the epileptic condition as such. They belong mainly to one of three domains. NONSPECIFIC PREVENTION OF SEIZURES: The first step is the identification of factors facilitating the occurrence of seizures. In the second step, strategies to control these factors are developed. Most common are disturbances of the sleep-wake cycle, especially reduction of sleep. Patients should follow a regular sleep schedule with deviations of not >2 h. Sometimes a sleep calendar is helpful. Night shifts are not compatible with seizure prevention in these cases. Sleep disturbances as a facilitating factor of seizures are particularly common in juvenile idiopathic generalized epilepsies, in which their avoidance is in many cases an indispensable part of the therapeutic regimen, along with appropriate drug treatment. They are the most common precipitating factor in adolescents and adults with a first epileptic [mostly generalized tonic-clonic (GTC)] seizure. In these instances, their avoidance is central to the secondary prevention of epilepsy developing from the single seizure, whereas the prescription of antiepileptic drugs (AEDs) is rarely effective. Other nonspecific facilitators of seizures include uncontrolled use of alcohol and extraordinary stress. Patients must learn how to cope with stressful events. SPECIFIC PREVENTION OF SEIZURES: In reflex epilepsies, specific precipitants of seizures are the targets of interventions. Thus, most patients with primary reading epilepsy begin to have, with prolonged reading, perioral reflex myoclonias, which enable them to stop reading and thus to avoid a GTC seizure. In photosensitive patients, seizures are often precipitated by television. These can be avoided by viewing from a distance and using a remote control, small screens in a well-lit room, and preferably with a 100-Hz line shift. Environmental flicker stimulation often comes unexpectedly, and it is advisable that the patients always wear sunglasses in brightly lighted surroundings. Polarized glasses seem to be more protective than plain sunglasses. If the patient has only photically induced seizures, treatment by specific prevention alone may be sufficient, but if spontaneous seizures also occur, drugs must be given in addition. ARREST OF SEIZURES: Focal seizures that develop sufficiently slowly to leave the patient time to react may be interrupted by "countermeasures." These, again, may be nonspecific (acting by relaxation, concentration, or a combination of both) or specific. The latter are individually tailored, based either on spontaneous experiences of the patient or on the anatomy of ictogenesis. Seizure propagation is blocked when a major part of the neurons involved is activated and not recruitable for spread of the epileptic discharge. Seizure arrest rarely is used alone but usually in combination with partially successful pharmacotherapy.

Adolescent↗