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Biomedical subjects

J Wimberly

Publications and source records attributed to J Wimberly.

8 recordsLinked to original sources
PubMed1999

Turbo-PUVA: dihydroxyacetone-enhanced photochemotherapy for psoriasis: a pilot study.

BACKGROUND: Dihydroxyacetone (DHA), a colorless sugar in "sunless" tanning lotions, binds to stratum corneum to form a UV-A-protective brown pigment. Bound DHA polymer is shed faster from hyperproliferative skin sites such as psoriatic plaques. We tested the hypothesis that selective shedding of DHA pigment during psoralen-UV-A (PUVA) treatment of psoriasis may allow higher UV-A doses, thus accelerating clearing while protecting uninvolved skin. Concurrent use of lactic acid was investigated as an aid in removing scale and residual DHA from psoriatic plaques. OBSERVATIONS: Thirty psoriatic patients with more than 20% body surface area involvement were recruited. The 6 PUVA study groups were (1) standard American style, (2) American style plus lactic acid, (3) DHA-PUVA or "topical ultraviolet-resisting barrier to optiimize PUVA" (Turbo-PUVA), (4) Turbo-PUVA with lactic acid, (5) European style, and (6) European style plus DHA. Combinations of lactic acid and European-style treatment were not studied. Each subject received up to 30 oral PUVA treatments twice weekly 3 days apart. The DHA-PUVA groups used 15% DHA lotion twice weekly. Lactic acid groups used 7% lotion daily except on treatment days. Psoriasis area and severity index scores were recorded weekly. Turbo-PUVA allowed higher UV-A exposures with minimal burns, showed faster clearing, and required fewer treatments for 90% clearing (P<.001). CONCLUSIONS: Protection of uninvolved skin by DHA during PUVA treatment allows higher UV-A exposures to be tolerated, demonstrates faster clearing, and requires fewer treatments to clear psoriasis. By reducing the total body dose received, Turbo-PUVA may also reduce long-term risks.

Adult↗
PubMed1990

Mechanistic investigation of doxycycline photosensitization by picosecond-pulsed and continuous wave laser irradiation of cells in culture.

In order to elucidate the photophysical mechanisms of cellular phototoxicity sensitized by doxycycline, MGH-U1 human bladder carcinoma cells in vitro were treated with 20.7 microM doxycycline and irradiated with either a pulsed (lambda = 355 nm, pulse duration = 24 ps) or a continuous wave (lambda = 351 nm) laser. Cumulative radiant exposure and irradiance were systematically varied in experiments with both lasers. Phototoxicity was assessed by epifluorescence microscopy of unfixed cells using rhodamine 123 labeling of mitochondria. With the continuous wave source, the cumulative radiant exposure required for induction of phototoxic injury was independent of irradiance. With the 24-ps-pulsed source, a significantly lower cumulative radiant exposure was required to induce the phototoxicity when the peak irradiance was 5.8 x 10(7) or 1.3 x 10(8) watts cm-2 compared with when peak irradiance was either lower (6.0 x 10(6) watts cm-2) or higher (7.6 x 10(8) watts cm-2). The measured fluorescence lifetimes of doxycycline in buffered saline solution were longer than the laser pulse duration of 24 ps. The increased efficiency of photosensitization at the optimal peak irradiance in the ps domain appears to result from sequential multiphoton absorption involving higher excited states of the singlet manifold. At the highest irradiance studied, on the other hand, reduced efficiency of photosensitization is attributed to increased photodegradation of doxycycline from higher excited states by processes such as photoionization. A model consistent with these observations is presented along with calculations, based on simple rate equations, that fit the essentials of the proposed model.

Cell Line↗
PubMed1989

Rhodamine dyes as potential agents for photochemotherapy of cancer in human bladder carcinoma cells.

The phototoxicity in vitro of rhodamine 123 and tetrabromo rhodamine 123 (TBR) was compared, in order to assess their photochemotherapeutic potential. Exposure to 514.5-nm radiation from an argon ion laser caused phototoxicity in MGH-U1 bladder carcinoma cells previously treated with either dye at 10 microM for 30 min. As assessed by colony formation and cellular morphology, TBR was markedly more phototoxic than rhodamine 123, reflecting increased intersystem crossing of TBR to the triplet manifold via spin-orbital coupling induced by the heavy bromine atoms. Photoreactions of TBR very efficiently generated singlet oxygen (1O2) in solution; furthermore, irradiation of TBR-treated cells was significantly more toxic when performed in the presence of deuterium oxide, an enhancer of damage caused by 1O2. Retention of fluorescence in TBR-treated cells was enhanced by irradiation, indicating that a stable photoproduct may be formed in reaction with cellular components.

Antineoplastic Agents↗
PubMed1986

Mitochondrial phototoxicity sensitized by doxycycline in cultured human carcinoma cells.

Cultured MGH-U1 (human urinary bladder carcinoma) cells were treated with doxycycline (DOTC) and long-wave UV radiation (UVA). At UVA doses of 1 J/cm2 and above, the cells showed mitochondrial damage, reflected by altered localization of the fluorescent probe rhodamine-123, and striking vacuolization of the cytoplasm. Cell membrane integrity, as monitored by exclusion of ethidium bromide, was maintained for several hours after mitochondrial damage was evident. These changes were potentiated by irradiation in the presence of deuterium oxide, and diminished by irradiation in the presence of sodium azide. Addition of catalase, superoxide dismutase, or mannitol did not alter the damage threshold. These data indicate that the mitochondrion is an earlier target of DOTC photosensitization than the cell membrane. The critical photochemistry appears to involve singlet oxygen.

Carcinoma, Transitional Cell↗
PubMed1984

Ultra violet radiation-induced defects in accessory cell function in the human proliferative response to tetanus.

Ultraviolet B radiation (290-320 nm) has been shown to interfere with accessory cell function of human peripheral blood mononuclear cells in the generation of a proliferative response to tetanus. By altering the timing of irradiation of adherent cells and using short pulses of antigen, we have identified a minimum of two u.v. sensitive accessory cell functions. The first involves antigen presentation and is not readily reversible with time in culture after irradiation. The second is demonstrated by the ability of low doses of u.v. radiation given after the tetanus toxoid pulse to inhibit an event(s) occurring independent of antigen processing. Both occur within a range of doses which would penetrate to the vasculature of the skin of humans exposed to the sun or to phototherapy.

Cell Adhesion↗
PubMed1983

Abnormal lymphocyte function following long-term PUVA therapy for psoriasis.

The surface markers and function of peripheral blood lymphocytes were examined in patients on long-term therapy with methoxsalen and UV-A radiation (PUVA). Ten patients with psoriasis were selected because they had received a high exposure to PUVA therapy, i.e., more than 200 treatments over 2-6 years with cumulative exposure doses of 1700-6000 J/cm2 UV-A radiation. Results were compared to those obtained with lymphocytes from untreated patients and UV-B treated patients with psoriasis. The PUVA-treated patients had low levels of E rosette-forming cells in the peripheral blood and markedly impaired lymphocyte responses following stimulation with optimal and suboptimal doses of mitogens. The sensitivity of lymphocytes to in vitro treatment with PUVA was similar in the three groups of patients. The results of this study indicate that long-term PUVA therapy alters the function and cell-surface markers or distribution of lymphocytes.

Adolescent↗