Predicting upper extremity motor improvement following therapy using EEG-based connectivity in chronic stroke.

BACKGROUND: Uncertain prognosis presents a challenge for therapists in determining the most efficient course of rehabilitation treatment for individual patients. Cortical Sensorimotor network connectivity may have prognostic utility for upper extremity motor improvement because the integrity of the communication within the sensorimotor network forms the basis for neuroplasticity and recovery. OBJECTIVE: To investigate if pre-intervention sensorimotor connectivity predicts post-stroke upper extremity motor improvement following therapy. METHODS: Secondary analysis of a pilot triple-blind randomized controlled trial. Twelve chronic stroke survivors underwent 2-week task-practice therapy, while receiving vibratory stimulation for the treatment group and no stimulation for the control group. EEG connectivity was obtained pre-intervention. Motor improvement was quantified as change in the Box and Block Test from pre to post-therapy. The association between ipsilesional sensorimotor connectivity and motor improvement was examined using regression, controlling for group. For negative control, contralesional/interhemispheric connectivity and conventional predictors (initial clinical motor score, age, time post-stroke, lesion volume) were examined. RESULTS: Greater ipsilesional sensorimotor alpha connectivity was associated with greater upper extremity motor improvement following therapy for both groups (p < 0.05). Other factors were not significant. CONCLUSION: EEG connectivity may have a prognostic utility for individual patients' upper extremity motor improvement following therapy in chronic stroke.

Effect of elliptic handle shape on grasping strategies, grip force distribution, and twisting ability.

A generic torque model for various handle shapes has been developed and evaluated using experimental data. Twelve subjects performed maximum isometric torques using circular and elliptic cylinders in medium and large sizes (circular: r = 25.4, 38.1 mm; elliptic: semi-major/minor axes = 30.9/19.3, 47.1/27.8 mm) finished with aluminium and rubber, in two opposite directions. Torque, grip force distribution, and finger position were recorded. Maximum torques were 25%, 7%, and 31% greater for the elliptic, large-size, and rubber-finished cylinders than for the circular, medium-size, and aluminium-finished cylinders, respectively. Greater torque for the elliptic cylinders was associated with 58% greater normal force that the subjects could generate for the elliptic than circular cylinders. The model suggests that greater torques for the large-size and rubber cylinders are related to long moment arms and greater frictional coupling at the hand-cylinder interface, respectively. Subjects positioned their hands differently depending on torque direction to maximise their normal force and torque generation. STATEMENT OF RELEVANCE: Desirable handle features for torque generation may be different from those for grip only. Design of handles per advantageous handle features (e.g., shape, size, and surface) may help increase people's torque strength and contribute to increased physical capacity of people.

Expression of the Qa-2k phenotype encoded by the Q5k gene on the surface of tumor cells derived from H-2k mice.

Immunological and biochemical characteristics of the Qa-2 murine nonclassical histocompatibility class 1 antigen expressed on tumor cells derived from H-2k (Qa-2-) mice were studied. It was found that the Qa-2 antigen on normal H-2b lymphocytes reacted with Qa-2-specific monoclonal antibodies (mAbs) 34-1.2, 59 (both specific to the alpha 1/alpha 2 region) and 141-15.8 (specific to the alpha 3 domain), and the Qa-2 antigen on H-2k tumor cells (Qa-2k antigen) reacted with mAbs 59 and 141-15.8, but not with 34-1.2. The normal Qa-2 antigen was susceptible to treatment with phosphatidylinositol-specific phospholipase C, but the Qa-2k antigen was insensitive to it. By Northern hybridization, polymerase chain reaction (PCR) studies on cDNA, Southern hybridization, Western blotting, and nucleotide sequence analysis, the Q5k gene was identified as the gene encoding the Qa-2k antigen expressed on BW5147 lymphoma cells derived from a mouse of AKR strain (H-2k, Qa-2-). The nucleotide sequence of PCR-amplified BW5147 Q5k cDNA showed complete agreement with the reported sequence of exons 1-5 of the Q5k gene of C3H/He. It also showed complete deletion of the region corresponding to exons 6 and 7, and a very short coding region in exon 8, resulting in very short cytoplasmic domain of the product compared with regular class 1 antigens. These characteristics were expected from the reported Q5k genomic sequence. These results revealed that the Qa-2k antigen was distinct from the normal Qa-2 antigen expressed on H-2b lymphocytes although it cross-reacted with some Qa-2-specific mAbs.

First trimester findings of decidual polyp: Caution to avoid polypectomy.

Obstetricians are sometimes faced with a dilemma in that polypectomy, which is a prerequisite for differentiating malignancy, may be associate with miscarriage or preterm delivery. We describe a case with a decidual polyp resulted in first trimester miscarriage after diagnostic polypectomy. Our experience with this patient provides us important information for clinical practice. That is, decidual polyp can be recognized as early as gestational week 5, the roots of cervical polyps should be meticulously observed, a polyp connected to the decidua is suggestive finding of decidual polyp, and suspected decidual polyp can be managed conservatively.

Airtraq optical laryngoscope: tracheal intubation by novice laryngoscopists.

OBJECTIVE: To evaluate the performance of the Airtraq optical laryngoscope for tracheal intubation by novice laryngoscopists, compared with that of the Macintosh laryngoscope. METHODS: Under supervision by staff anaesthetists, non-anaesthesia physicians performed tracheal intubation using either the Airtraq optical laryngoscope (n = 100) or the Macintosh laryngoscope (n = 100). The time required for airway instrumentation, the number of attempts until successful intubation and erroneous oesophageal intubation were investigated. RESULTS: The time to secure the airway was shorter with the Airtraq optical laryngoscope than with the Macintosh laryngoscope (p<0.001). The number of attempts until successful intubation was smaller with the Airtraq optical laryngoscope than with the Macintosh laryngoscope (p<0.001). Erroneous oesophageal intubation was less with the Airtraq optical laryngoscope than with the Macintosh laryngoscope (p<0.01). CONCLUSION: The Airtraq optical laryngoscope reduces the time to secure the airway and the incidence of failed tracheal intubation by novice laryngoscopists.

Effects of upper body strength, hand placement and foot placement on ladder fall severity.

BACKGROUND: A plurality of fatal falls to lower levels involve ladders. After a slip/misstep on a ladder, climbers use their upper and lower limbs to reestablish contact with the ladder. RESEARCH QUESTION: This study investigates the impact of upper body strength, hand placement and foot placement on fall severity after a ladder climbing perturbation. METHODS: Participants performed upper body strength tests (breakaway and grip strength) and climbed a vertical, fixed ladder while a misstep perturbation was applied under the foot. After the perturbation, three hand placement and two foot placement responses were generally observed. Common hand placement responses included the hand moving two rungs, one rung, or did not move to a different rung. Foot placement responses included at least one foot or no feet reestablished contact with the ladder rung(s). Fall severity was quantified by the peak harness force observed after the perturbation. RESULTS: Increased strength, reestablishing at least one foot on the ladder, and ascending (compared with descending) the ladder was associated with a reduction in fall severity. An interaction effect indicated that the impact of hand placement was altered by climbing direction. Moving the hand one rung during ascent and moving the hand two rungs during descent was associated with an increased fall severity. Cases where the hand decoupled from the ladder was associated with higher fall severity. Upper body strength assessed using a portable grip dynamometer was sufficient to predict fall severity. DISCUSSION: This study confirms the multifactor role of upper body strength, hand placement and foot placement in preventing falls from ladders. Furthermore, a portable dynamometer shows potential to screen for high-risk individuals. Results of this investigation may guide targeted interventions to prevent falls from ladders.

Long-term Follow-up of Complicated Crown Fracture With Fragment Reattachment: Two Case Reports.

Two cases of complicated crown fracture of the maxillary incisors were restored using the fragment reattachment technique. Root canal treatment was performed, and the fractured fragment was bonded to the tooth structure using a dentin adhesive system and a flowable composite resin, followed by the insertion of a fiber post using dual-cured resin cement. Reattached fragments have shown reliable prognosis without inflammatory signs around bonded junctions after long-term follow-up.

A comparison of cervical spine movement during laryngoscopy using the Airtraq or Macintosh laryngoscopes.

The Airtraq laryngoscope has an oropharyngeal airway-shaped blade that provides a non-line-of-sight view of the glottis. The configuration of the blade should mean that less movement of the cervical spine is required during laryngeal visualisation. We compared the degree of cervical spine movement in laryngoscopy performed using the Airtraq and conventional Macintosh laryngoscope. In 20 patients requiring general anaesthesia and tracheal intubation, we measured cervical spine movement using radiography in the same patient during consecutive procedures using the two laryngoscopes. Although significant movement of the cervical spine from baseline was noted during all procedures (p < 0.05), cervical spinal extension with the Airtraq was 29% less than that measured during Macintosh laryngoscopy between the occiput and C4, and 44% less at the C3/C4 motion segment (p < 0.05). Anterior deviations of the vertebral bodies from baseline were 32%, 35%, 38% and 40% less at the atlas, C2, C3, and C4 vertebrae, respectively, during Airtraq laryngoscopy than those measured during Macintosh laryngoscopy (p < 0.01). Our study demonstrated that laryngoscopy using the Airtraq laryngoscope involves less movement of the cervical spine compared to conventional procedures using a Macintosh laryngoscope.

Isolation of two new natural pteridines from photosynthetic bacteria, Rhodopseudomonas sphaeroides.

Two new natural pteridines have been isolated from the cultured medium of Rhodopseudomonas sphaeroides GM-1. The compounds are tentatively identified as 2-amino-4-hydroxy-6-hydroxy-6-(1,2, 3,4-tetrahydroxybutyl)pteridine and 2-amino-4-hydroxy-6-(3-hydroxy-4-phosphonoxy-1-butenyl)pteridine by degradative experiments and by electrophoretic and paper chromatographic comparison with authentic materials.

Effect of continuous infusion of propofol on its concentration in blood with and without the liver in pigs.

In living donor liver transplantation, propofol, an intravenous anesthetic drug, has recently been used in both donors and recipients. Propofol is known to have intra- and extrahepatic metabolic pathways, but the effect of its continuous infusion during a long-term anhepatic state is yet to be determined. Recently, we successfully established a simplified pig model of the complete anhepatic state. In this state, we first evaluated hemodynamic parameters relating to the pharmacokinetics of continuously infused propofol (6 mg.kg(-1) x h(-1)). No significant changes in the concentration of hemoglobin or in hemodynamic parameters other than the heart rate were observed during the anhepatic phase when porpofol was continuously infused at the rate that maintains the state. Blood propofol concentrations in the mixed vein, artery, and portal vein were stable during the anhepatic phase. Finally, we confirmed the pharmacokinetics of continuously infused propofol using orthotropic liver transplantation in miniature pigs. The propofol concentration did not change markedly during the transplant procedure. In conclusion, the pharmacokinetics of continuously infused propofol was almost stable with and without the liver in pigs. Extrahepatic metabolism of propofol might help prevent changes in propofol concentrations.

Evaluation of intraoperative infusion solution using a complete anhepatic model in baby pigs.

Compared to cadaveric liver transplantation, living-related liver transplantation (LRLT) has the physiological advantage of avoiding hemodynamic changes due to the nonsystemic clamping of the inferior vena cava (IVC). However, metabolic changes in the level of blood glucose and lactate usually occur during the anhepatic phase in LRLT. For pediatric patients, intraoperative infusions have the potential to maintain immature homeostasis during LRLT. In the present study, a complete anhepatic model of baby pigs with nonsystemic clamping of IVC, which mimics the procedure of pediatric LRLT, was established using a heparin-coated tube as an internal shunt lactate Ringer solution (LR, Lactec), acetate Ringer solution (AR, VeenF), and a solution comprising acetate Ringer with 1% glucose (AR-G, Phisio140) were tested using piglets. Hemodynamic and metabolic (blood gas analysis, electrolytes, blood lactate, and glucose) changes were observed during the anhepatic phase. Although no major difference was observed in hemodynamic parameters, arterial blood gas data, or concentration of electrolytes among the three solution groups, significant progressive hyperlactatemia was observed in the LR group. Also, though severe hypoglycemia was found in the LR and AR groups, the AR-G group maintained blood glucose levels throughout the anhepatic phase. To conclude, using the simplified pig anhepatic model, we evaluated various solutions for pediatric LRLT.

Quinolone-photoconjugated major histocompatibility complex class II-binding peptides with lysine are antigenic for T cells mediating murine quinolone photoallergy.

Fluoroquinolone antibacterial agents cause photosensitivity dermatitis as an adverse effect and can function immunologically as photohapten. In a murine model of quinolone photoallergy, Langerhans cells are photomodified with a systemically given quinolone upon ultraviolet A irradiation of skin and thus present photohaptenic moieties to sensitize and restimulate T cells. The aim of this study is to determine the site of peptides/proteins photobound to quinolones and to assess the T cell antigenicity of quinolone-photocoupled peptides using Langerhans cells as photoadduct-presenting cells. On an amino acid composition analysis, lysine was preferentially degraded in bovine serum albumin that was ultraviolet A-conjugated with a representative quinolone ofloxacin. An affinity chromatographic study using a quinolone photoadduct-specific monoclonal antibody as ligand demonstrated preferential photocoupling of ofloxacin with a lysine-containing peptide. CD4+ T cells were purified from lymph nodes of BALB/c mice sensitized subcutaneously with ofloxacin-photomodified epidermal cells and from those sensitized epicutaneously via barrier-disrupted skin with a major histocompatibility complex class II (I-Ad)-binding, ofloxacin-photoconjugated peptide. These immune T cells proliferated in vitro in response to Langerhans cells loaded with class II-binding, lysine-containing peptides when photomodified with ofloxacin. Furthermore, epicutaneous application of the ofloxacin-photoconjugated peptide was able to prime mice for subsequent elicitation of photoallergy evoked with systemic ofloxacin and ultraviolet A light. This study suggests that lysine affords quinolone photocoupling of peptides and quinolone-photomodified peptides on class II molecules stimulate pathogenetic T cells in quinolone photoallergy.

Formation of antigenic quinolone photoadducts on Langerhans cells initiates photoallergy to systemically administered quinolone in mice.

Quinolone antibacterial agents are well known to cause photoallergy as a side-effect. Murine photoallergy to fluoroquinolones is a T cell-mediated immune response, evoked either by systemic fluoroquinolone and subsequent exposure of skin to ultraviolet A light or by subcutaneous injection of fluoroquinolone-photomodified epidermal cells. In this photosensitivity, epidermal Langerhans cells may be photomodified initially with the drug and thus present photohaptenic moieties to sensitize and restimulate T cells. Although we have shown that Langerhans cells photocoupled in vitro with fluoroquinolones are capable of stimulating sensitized T cells, it remains unclear whether systemically given fluoroquinolone photomodifies Langerhans cells upon ultraviolet A irradiation of the skin and the Langerhans cells become photohapten-bearing, T cell-stimulatory cells. In a murine model of fleroxacin photoallergy induced by intraperitoneal injection of the drugs plus ultraviolet A irradiation of skin, we found that Langerhans cells as well as keratinocytes are photoderivatized with fleroxacin as demonstrated with a fluoroquinolone-specific monoclonal antibody. Langerhans-cell-enriched epidermal cells prepared from mice treated with fleroxacin and ultraviolet A induced proliferation of sensitized T cells, indicating that photomodified Langerhans cells are functional. There was an optimal range of ultraviolet A dose to quantitatively and qualitatively form fleroxacin-photomodified Langerhans cells, as excess ultraviolet A rather reduced the photoantigen-presenting capacity of Langerhans cells presumably because of drug phototoxicity. Our study suggests that Langerhans cells serve as photoantigen-presenting cells in drug photoallergy.

Altered permeability and disordered cutaneous immunoregulatory function in mice with acute barrier disruption.

In vivo and in vitro T-cell-activating ability of murine epidermal cells (EC) was investigated in acutely barrier-disrupted skin by extraction of epidermal lipids with acetone or removal of corneocytes by tape stripping. Contact sensitivity (CS) to 2,4-dinitrofluorobenzene (DNFB) and picryl chloride (PCl) and contact photosensitivity (CPS) to tetrachlorosalicylanilide (TCSA) were significantly augmented when challenged or sensitized at sites treated with acetone 24 h before, compared with the intact skin. CS to DNFB was also enhanced by tape stripping, but not by water rubbing, suggesting that physical stress or a toxic effect of acetone was not responsible for the augmentation. Semi-quantification of TCSA-EC photoadducts showed markedly increased permeability of hapten in the epidermis 24 h after acetone treatment. Bioactive IL-1alpha was more pronounced in barrier-disrupted than in intact skin. Lymph node T cells from PCl-sensitized mice proliferated significantly more in a hapten-specific and co-stimulatory molecule-dependent manner in response to trinitrophenylated (TNP) EC from acetone-treated skin than to those from untreated skin. Immunofluorescence staining of epidermal sheets and flow cytometric analysis of dispersed EC showed that subpopulations of Langerhans cells (LC) in acetone-rubbed or tape-stripped skin expressed major histocompatibility complex class II CD54 and CD86 molecules at levels higher than the rest of LC and LC from water-treated or untreated epidermis. Therefore, not only increased permeability of hapten through the epidermis but also altered immune functions of EC potentiate T-cell activation in acute barrier disruption. Such augmentation of immune reactivity may be critical to elimination of environmental noxious agents that penetrate easily into the barrier-disrupted epidermis.

Treatment of T lymphocytes with 8-methoxypsoralen plus ultraviolet A induces transient but biologically active Th1-skewing cytokine production.

8-Methoxypsoralen plus ultraviolet A light is suggested to shift T lymphocytes from Th2 to Th1 cells. To clarify this issue, we examined the effects of 8-methoxypsoralen/ultraviolet A on the expression/production of cytokines in peripheral blood mononuclear cells from normal subjects and a Sézary syndrome patient. 8-Methoxypsoralen/ultraviolet A augmented the expression of mRNAs for interferon-gamma and interleukin-2 and reduced those for interleukin-4 and interleukin-10. It seems that this enhancement of Th1 cytokines is caused by increment of cytokine production by Th1 cells but not by conversion of Th2 cells to produce Th1 cytokines. The number of interferon-gamma-secreting lymphocytes was markedly increased in 8-methoxypsoralen/ultraviolet A-treated peripheral blood mononuclear cells 20 h after treatment, whereas that of Th2 cytokine-producing cells was decreased. Accordingly, the amount of interferon-gamma was elevated in culture supernatants from 8-methoxypsoralen-phototreated peripheral blood mononuclear cells, whereas interleukin-4 was significantly reduced. This enhanced production of interferon-gamma, however, was found only until 3 d after 8-methoxypsoralen phototreatment and was declined by 5 d after treatment. Finally, 8-methoxypsoralen/ultraviolet A treatment of T cells regulated their ability to induce keratinocyte CD54 expression. Our results show that 8-methoxypsoralen/ultraviolet A has a transient but biologically active Th1-skewing action in human T cells, suggesting that 8-methoxypsoralen/ultraviolet A exerts a beneficial therapeutic effect on Th2-mediated or Th2-malignant diseases.

Biphasic changes in hypothalamo-pituitary-adrenal function during the early recovery period after major abdominal surgery.

Regulatory mechanisms of the hypothalamo-pituitary-adrenal (H-P-A) axis during and after major abdominal surgery were studied in a group of patients who underwent upper abdominal surgery. We first examined the general profile of the changes of the H-P-A axis from the day before surgery to the seventh day after surgery. On the day of surgery, plasma levels of CRH, ACTH, and cortisol were all significantly elevated after skin incision (phase I). During the next 2 days, plasma cortisol levels remained significantly elevated, and the both plasma CRH and ACTH levels were suppressed below the control levels obtained on the day before surgery (phase II). Several additional studies, carried out to analyze the mechanism that maintains the high plasma cortisol levels, revealed the following features of the H-P-A axis during phase II. Plasma free cortisol levels in this phase were higher than those during the preoperative period. The exogenously administered hydrocortisone clearance rate in phase II did not differ from that observed on the day before surgery. Dexamethasone administration resulted in a decrease in plasma cortisol levels similar to that observed preoperatively. Conversely, the ACTH-stimulated cortisol increase was significantly greater in phase II than that observed preoperatively. These results suggest that during and after major surgical stress, the H-P-A axis undergoes a biphasic change in the pattern of the stress response and during the second phase, not the continuous hypothalamo-pituitary drive but the increased adrenal responsiveness to ACTH is responsible at least in part for maintaining the elevated plasma cortisol level.

Downregulation of innate and acquired antitumor immunity by bystander gammadelta and alphabeta T lymphocytes with Th2 or Tr1 cytokine profiles.

It has been thought that natural killer (NK) cells appearing early in tumor lesions play a pivotal role in the innate immunity against tumor cells. Although NK cells serve as the first tumoricidal effector cells, they subsequently promote a shift in effectors from themselves to tumor-specific cytotoxic T lymphocytes (CTLs) that mediate the acquired immunity. The mechanism of this shift has not been fully elucidated, however, NK cell-derived T helper (Th) 1 cytokines such as interferon (IFN)-gamma seem to play a key role. Another NK-lineage, termed natural killer T (NK T) cells, may also participate in the innate period when they acquire the ability to secrete Th1 cytokines. Interleukin-4 (IL-4) and IL-10, belonging to Th2, and transforming growth factor-beta (TGF-beta), belonging to T regulatory (Tr) 1 cytokines, are known to suppress the development of NK, NK T cells, as well as CTLs and to block Th0 cell differentiation to Th1 cells, suggesting that tumor cells can evade the innate and acquired immunity by virtue of cells producing these inhibitory cytokines. In early tumor lesions of murine B16 melanoma, gammadelta T and alphabeta intermediate (int) T cells that co-infiltrate with NK and NK T cells can produce Th2 cytokines and inhibit the innate immunity. In MM2 mammary tumor-bearing mice, gammadelta T cells appearing both lesionally and systemically secrete Tr1-type cytokines and depress the acquired immunity. These Th2- or Tr1-type gammadelta T and alphabeta(int) T cells downregulate the tumoricidal cells by means of both their secreted cytokines and express major histocompatibility complex (MHC) class I molecules.

Tubulin and high molecular weight microtubule-associated proteins as endogenous substrates for protein carboxymethyltransferase in brain.

The endogenous substrate for protein carboxymethyltransferase in brain was examined. Several polypeptides were methylated when brain slices were incubated with L-methionine or when subcellular fractions of brain, such as the cytosolic fraction, were incubated with S-adenosyl L-methionine. Two methyl-accepting proteins in the cytoplasm were identified as tubulin and high molecular weight microtubule-associated proteins (300 kDa), which are components of microtubules. Tubulin behaved as a 43 kDa protein in acidic polyacrylamide gel electrophoresis, but as a 55 kDa protein in SDS-polyacrylamide gel electrophoresis. The methyl moiety transferred to these proteins from L-methionine was labile at alkaline pH. The high molecular weight microtubule-associated proteins showed higher methyl-accepting activity than tubulin or ovalbumin, which was used as a standard substrate: about 20 mmol of high molecular weight microtubule-associated proteins, 2 mmol of tubulin and 10 mmol of ovalbumin were methylated per mol of each protein in 30 min under the experimental conditions used.

Lymphocyte stimulation test with drug-photomodified cells in patients with quinolone photosensitivity.

Quinolone antibacterial agents, known to elicit photosensitive dermatitis as an adverse effect, have both phototoxicity and photoallergenicity. The latter potency is mainly derived from their photohaptenic moiety; quinolones covalently bind to protein and cells upon exposure to ultraviolet A (UVA) light. Our previous study has shown the in vivo and in vitro antigenicity of quinolone-photomodified cells in mice. Here, we examined the presence of sensitized lymphocytes that react with quinolone-photomodified autologous cells in patients with photosensitivity to quinolones. A flow cytometric analysis using a monoclonal antibody specific to quinolone photoadducts demonstrated that peripheral blood mononuclear cells (PBMC) were successfully photomodified with quinolones upon exposure to UVA. PBMC from quinolone-photosensitive patients were cocultured with autologous PBMC photomodified with the causative drug. Modest but significant proliferative responses of responder lymphocytes were found in patients photosensitive to lomefloxacin, fleroxacin, and enoxacin, indicating photoallergic mechanism in these patients. On the other hand, sparfloxacin-photosensitive patients exhibited negative lymphocyte stimulation test, suggesting that its photosensitivity is mainly phototoxic. When UVA-preirradiated quinolones were used as stimulators, only fleroxacin exceptionally stimulated patients' PBMC, indicating its prohaptenic as well as photohaptenic properties. These findings suggest the presence of circulating sensitized T cells in patients with photosensitivity to certain quinolones.

Photoactivational cytokine-modulatory action of 8-methoxypsoralen plus ultraviolet A in lymphocytes, monocytes, and cutaneous T cell lymphoma cells.

Treatment with 8-methoxypsoralen (8-MOP) and ultraviolet A light (UVA) has been reported to modulate cytokine production in various cells. Our study was conducted to see the effects of 8-MOP/UVA on the expression/production of cytokines in peripheral blood lymphocytes and monocytes in relation to the therapeutic mechanisms of extracorporeal photochemotherapy. 8-MOP/UVA augmented the expression of mRNAs for interferon-gamma (IFN-gamma) and interleukin (IL)-2 and reduced those for IL-4 and IL-10 in peripheral blood mononuclear cells (PBMCs) from normal subjects and Sézary syndrome patients. This enhancement of Th1 cytokines was caused by increment of cytokine production by Th1 cells but not by conversion of Th2 cells to produce Th1 cytokines. The number of IFN-gamma-secreting lymphocytes was markedly increased in 8-MOP/UVA-treated PBMCs 20 h after treatment, and its amount was elevated in culture supernatants. However, this enhanced production of IFN-gamma was found only until three days after 8-MOP phototreatment, and its level was rapidly declined by five days after treatment. In addition to this Th1-polarized action, 8-MOP/UVA-treated PBMCs produced enhanced amounts of IL-8 upon stimulation with anti-CD3/CD28 antibodies. Phototreated CD4+ but not CD8+ cells provided excellent T cell help for monocytes to produce IL-8 via a direct cell-to-cell contact mechanism. These findings suggest that 8-MOP/UVA has a transient but biologically active Th1-skewing action in T cells, and the phototreated T cells simultaneously stimulate monocytes to produce IL-8. It is suggested that 8-MOP/UVA exerts a beneficial therapeutic effect on malignant Th2 neoplasms as a Th1-skewing cytokine modifier and that 8-MOP-phototreated CD4+ T cells allow monocytes to become effective tumor antigen-presenting cells for tumor-specific cytotoxic T cells.