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Sirs, Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia due to an idiopathic chronic granulomatous inflammation of the cavernous sinus [9]. THS usually improves with corticosteroids, however, in cases showing an insufficient effect of corticosteroid therapy or side effects, alternative therapies such as immunosuppressive agents [3] or focal radiation therapy have been reported [2, 5–7]. We describe a patient with THS who was successfully treated with radiation monotherapy. A 36-year-old man with chronic hepatitis B and impaired glucose tolerance since age 30 developed acute left orbital pain and double vision at the end of July 2006. Neurologic examination on 3 August 2006 demonstrated only mild restriction of abduction of the left eye. Magnetic resonance imaging (MRI) of the brain showed no abnormality including the cavernous sinus region at that time. His illness progressed rapidly and he was admitted to our hospital on 14 August 2006. On admission, body temperature and blood pressure were normal. Neurologic examination demonstrated almost complete ophthalmoplegia in all directions and blepharoptosis without pupil abnormality on the left. Spontaneous left ophthalmic pain was also reported. There were no ophthalmic symptoms on the right and there were no symptoms of lower cranial nerves on both sides. Urinalysis and routine hematological examination were normal. Blood chemistry examination demonstrated mild elevation of aspartate aminotransferase (60 IU/L; normal range 11–34 IU/L), alanine aminotransferase (151 IU/L; normal range 6–39 IU/L) and glycohemoglobin A1c (6.1%; normal range 4.3–5.8%). Surface antigen and core antibody of hepatitis B virus were positive. The following immunological and inflammatory investigations were normal or negative; antinuclear antibody, cytoplasmic and perinuclear antineutrophil cytoplasmic antibody, angiotensin converting enzyme level and b-D-glucan. Chest radiography and Gallium scintigraphy of the whole body showed no abnormality suggestive of systemic inflammatory disease. Cerebrospinal fluid examinations were normal including cytology and culture for bacteria and mycobacteria. Brain MRI showed abnormal soft tissue enhanced with gadolinium within the left cavernous sinus (Fig. 1). Based on a diagnosis of THS, we first considered corticosteroid therapy for THS with simultaneous antiviral therapy for hepatitis; however, the patient refused corticosteroid therapy because of the possible exacerbation of hepatitis. One week after admission, the left pupil was dilated and light response was diminished, indicating progression of THS. Thereafter, the patient received a total of 30 Gy in 15 fractions focused on the left cavernous sinus by three-dimensional conformal radiotherapy (3D-CRT). Left blepharoptosis and ophthalmoplegia gradually improved within 2 weeks after the initiation of radiation therapy; blepharoptosis had almost completely disappeared by the middle of October 2006. Ophthalmoplegia also Y. Furukawa W. Yamaguchi K. Ito T. Hamada H. Miyaji Department of Neurology, Fukui Prefectural Hospital, Fukui, Japan

Langerhans cells (LCs) are activated in the epidermis by external and internal stimuli, such as antigens and cytokines, respectively. To reveal the morphologic and functional properties of in vivo-activated LCs during inflammation, we injected the streptococcal preparation OK-432 intradermally into the earskin of mice and performed time-course analyses by immunofluorescence and electron microscopy. Cellular infiltrate appeared in the dermis at 6 h after OK-432 injection and had progressively extended to the dermoepidermal junction at 12 and 24 h. Immunostaining for class II antigen revealed that LCs were enlarged and extended long dendrites during inflammation. Acidic compartments such as lysosomes and multivesicular bodies also increased in number and Golgi apparatuses developed as demonstrated by electron microscopy and morphometric analysis. Birbeck granules, although not showing numerical changes, were translocated from the Golgi area to the subplasmalemmal area. After epicutaneous application of cationic ferritin, LCs often contained endosomes as the result of engulfment by the cytoplasmic projections. The present results indicate that nonspecifically induced dermal inflammation is capable of inducing activation of LCs in vivo, and that in vivo-activated LCs have the capacity for active endocytosis and intracellular digestion or processing.

The proliferation and cell cycle phase composition of human dermal fibroblasts cultured on or in type I collagen lattices (reconstituted dermis model) were examined. On collagen lattices, as compared with conventional cultures on plastic dishes, the proliferation of human dermal fibroblasts was suppressed, being arrested at about one-half the saturation density after 10 days of culture. In collagen lattices, proliferation was further suppressed, being nearly arrested within 4-7 days of culture. Cells were analyzed for cell cycle phases by two-color flow cytometry using DNA staining and S phase cell staining with FITC-conjugated antibromodeoxyuridine antibody. After 5 days of culture, the number of S phase cells on collagen lattices was 49.3% of that on plastic dishes, with an increase in G0G1 phase cells of 79.8%. In collagen lattices, the number of S phase cells was very small (4.3% of all cells), and most of the cells accumulated in G0G1 phase. These findings suggest that the cell cycle of fibroblasts is arrested at G0G1 phase by their interaction with collagen. On the basis of these results, the reconstituted dermis model using collagen lattice is considered to be analogous to the dermis in vivo with respect to cell growth and cell cycle phase composition.

To elucidate the interaction between melanoma and its matrix, we cultured B16 murine melanoma cells on and in type I collagen gel and evaluated specified functions of melanoma cells; tyrosinase activity and melanin-synthesizing capacity. Proliferation of cells cultured in these environments was markedly suppressed compared with that of cells cultured conventionally on plastic. On the other hand, the tyrosinase activity of cells cultured in or on collagen gel was two to three times higher than that of cells cultured on the plastics, while their melanin production was approximately double that achieved during conventional culture of cells. In conclusion, collagen gel influenced the growth and cell-specific functions of the melanoma cell. The culture system using collagen gel as substrate may be useful for the investigation of the interaction between melanoma and its matrix.

The effects of antitumor agents are usually assayed on soft agar culture or monolayer culture on plastic. However, such an environmental condition cannot be found in vivo and could be too severe for cells to survive. Recently, studies have indicated that culture of cells in or on a collagen gel provides a matrix-like environment and enables the cells to exhibit fully their differentiating functions not observed on plastic [1, 4, 9, 11, 12]. To evaluate the effect of antitumor drugs under the conditions resembling those occurring in the process of infiltrating the dermis in vivo as much as possible, we cultured B16 melanoma cells in type I collagen gel and compared the effects of dacarbazine (DTIC) [3, 8] and all-trans-retinoic acid (RA) [7] with those on the conventional plastic dishes. Three-dimensional culture in type I collagen gel was performed according to the method of Elsdale and Bard [4] after modification as described previously [6]. Briefly, 0.3% pepsinized type I collagen solution (derived from porcine tendon, Nitta Gelatine, Osaka, Japan), HEPES/ NaOH neutralizing solution, concentrated Eagle's medium, cell suspension, and fetal calf serum (FCS) were mixed at below 4 ~ C. One millilitre of the mixture was poured into a 35-ram bacteriological dish (Falcon) and incubated at 37 ~ C. The final collagen concentration was 2.0 mg/ml and the initial cell density was 2 x 10 s cells/ml. After gelling, 2 ml of Eagle's medium supplemented with 10% FCS was added. Addition of DTIC or RA was started on day 4. DTIC was activated with exposure to white light [8]. Culture medium supplemented with FCS and these reagents was changed every other day. At indicated times gels were digested by collagenase at 37 ~ C for 40 rain and released viable cells were counted with a hemocytometer using the dye exclusion test.

Mesure de l'activite de l'ornithine de carboxylase (ODC) et du taux d'ARN messager de l'ODC au niveau de la peau de souris apres irradiation par les ultraviolets. On note une augmentation du taux de l'ARN messager, et dans des proportions plus importantes une augmentation de l'ODC au niveau de l'epiderme des regions cutanees irradiees