Inhibition of the CXCR3-mediated pathway suppresses ultraviolet B-induced pigmentation and erythema in skin.

BACKGROUND: Skin pigmentation by ultraviolet (UV) B radiation is caused in part by inflammation mediated by chemokines and cytokines secreted by keratinocytes in the irradiated area. However, such inflammatory processes have not been well documented. OBJECTIVES: To elucidate the inflammation processes caused by UVB irradiation using skin-lightening agents that suppress melanin synthesis after UVB irradiation. METHODS: Utilizing a three-dimensional (3D) skin model, agents that suppressed formation of sunburn cells (SBC) after UVB irradiation were screened. Molecules whose expression was upregulated by UVB irradiation and attenuated by pretreatment with the agent were then screened by gene microarray to explore the mechanism of UVB irradiation. Messenger RNA expression of the molecules identified to be responsible for melanin biosynthesis was knocked down with a Tet-off shRNA lentivirus construct to confirm the involvement of the molecule in the pigmentation pathway following UVB irradiation. RESULTS: Paeonia suffruticosa Andrews (PSA) pretreatment suppressed SBC formation in the 3D skin model, and erythema formation and pigmentation in volunteers exposed to UVB irradiation. Comprehensive gene analysis after UVB irradiation showed upregulation of CXCR3 and its ligands, CXCL9/monokine induced by interferon (IFN)-γ (MIG), CXCL10/10-kDa IFN-γ-induced protein (IP-10) and CXCL11/inducible T-cell α-chemoattractant (I-TAC). Upregulation of these genes was partially suppressed by PSA pretreatment. Melanin biosynthesis increased upon stimulation of CXCR3 ligands (MIG, IP-10 or I-TAC) and decreased following CXCR3 downregulation by shRNA knockdown. CONCLUSIONS: UVB irradiation activates CXCR3-mediated signalling that leads to melanin synthesis. PSA pretreatment shows a lightening effect partly by attenuating CXCR3-mediated signalling at the transcriptional level.

Gastric carcinosarcoma with neuroendocrine differentiation as the carcinoma component and leiomyosarcomatous and myofibroblastic differentiation as the sarcomatous component.

Gastric carcinosarcoma with neuroendocrine differentiation is a very rare neoplasm. In this article we present such a case. The gastroendoscopic examination of a 59-year-old Japanese man disclosed gastric cancer during follow-up after operation for rectal cancer. Subsequently, total gastrectomy was carried out because of gastric cancer. A large tumor measuring 9.2 x 8.4 cm was observed in the posterior wall of the upper portion of the stomach. The tumor was composed of carcinoma and sarcomatous cells, and the histological transition of both components was observed. Immunohistochemically, carcinoma and sarcomatous cells were positive for cytokeratin CAM5.2. The carcinoma contained adenocarcinoma and malignant cells with neuroendocrine differentiation. The sarcomatous component showed leiomyosarcomatous and myofibroblastic differentiation. The present tumor is the fifth case of gastric carcinosarcoma with neuroendocrine differentiation and the first case of gastric carcinosarcoma with myofibroblastic differentiation. Pathologists should bear in mind that gastric carcinosarcoma may show various types of differentiation.

[Three cases of emergency video-assisted thoracoscopic surgery for spontaneous hemopneumothorax].

We experienced 3 cases of video-assisted thoracoscopic surgery for spontaneous hemopneumothorax. All the patients had received emergent operations because of massive intrathoracic bleeding. At the operation, a 3 cm-minithoracotomy and 2 trocar ports were fashioned. In the head up position, massive blood clots in the apex in the thoracic cavity was removed by using grasping forceps and the source of bleeding point was detected easily. The bleeding was successfully stopped. It was difficult to remove massive blood clots from trocar port by suction, however it was easy to remove massive blood clots from a 3 cm-minithoracotomy window by using a large grasping forceps. Post operative course was satisfactory and the all patients discharged within 2 weeks after admission. We concluded that the spontaneous hemopneumothorax may be a good indication for video-assisted thoracoscopic surgery.

[Chronic eosinophilic pneumonia associated with rheumatoid arthritis].

We encountered a 45-year-old woman with chronic eosinophilic pneumonia associated with rheumatoid arthritis. In May 1997, she was given a diagnosis of rheumatoid arthritis and prescribed non-steroidal anti-inflammatory drugs. After a month, she visited our hospital because of fever and cough. A chest roentgenogram and computed tomographic scan on first admission revealed peripheral infiltrative shadows in the upper fields of both lungs. Approximately 30% of peripheral blood cells were eosinophils. Furthermore eosinophils were elevated in bronchoalveolar lavage fluid and transbronchial lung biopsy specimens. A conclusive diagnosis of chronic eosinophilic pneumonia was made on these grounds. The patient responded well to steroid treatment, but was readmitted a week later because of worsening joint pain and skin eruptions in the lower extremities of both legs. A skin biopsy showed perivascular and interstitial eosinophil infiltration. The combination of steroids, a disease modifying anti-rheumatic drug, and a non-steroidal anti-inflammatory drug proved to be effective.

The role of macrophages in increased mitogen response of rat splenic lymphocytes following in vitro incubation with vitamin E.

The role of macrophages (M phi) in the enhancement of lymphocyte proliferation by alpha-tocopherol (VE) was investigated using rat splenocytes. The proliferation of whole splenocytes was significantly higher than that of M phi-depleted splenocytes at all concentrations of concanavalin A (Con A; 0.5-10 micrograms/ml). When whole and M phi-depleted splenocytes were preincubated with VE (2 micrograms/ml) for 24 h, the proliferation of whole splenocytes was significantly enhanced compared to that of whole splenocytes preincubated with medium alone. In contrast, M phi-depleted splenocytes did not show any increase of proliferation following in vitro pretreatment with VE. When the splenic: M phi pretreated with both VE (2 micrograms/ml) and Con A (10 micrograms/ml) for 24 h were further incubated with splenic lymphocytes, their proliferation was significantly enhanced compared to that of splenic lymphocytes cultured with splenic M phi pretreated with Con A. In this experiment, the medium containing 2-mercaptoethanol (2-ME) had the ability to enhance splenic lymphocyte proliferation, which masked the enhanced effect of VE on splenic: lymphocyte proliferation. Furthermore, in vitro treatment of VE could not decrease the production of prostaglandin E2, but could enhance the production of interleukin 1 from splenic M phi. These results suggest that M phi play an important role in the proliferation of splenic lymphocytes following in vitro incubation with VE, which is closely associated with the action of VE as an immunomodulator rather than antioxidant.

[Diffuse subendocardial ischemia in a patient with aortic valve stenosis without coronary artery disease by exercise 201Tl SPECT].

A case of aortic valve stenosis without coronary artery disease was confirmed to have diffuse subendocardial ischemia by exercise Thallium-201 myocardial single photon emission computed tomography. A 72-year-old woman, who had been diagnosed as aortic valve stenosis, was admitted because of chest pain during exercise. In cardiac catheterization findings, the patient angiographically had normal coronary arteries and no asynergy of left ventricular wall motion. The peak flow velocity in continuous wave Doppler echocardiography was about 5.0 m/sec at aortic valve level, providing a pressure drop of 100 mmHg across a stenotic valve with calculating on a modified Bernoulli equation (PG = 4V2). Thallium-201 myocardial SPECT images during exercise showed a transient "dilation and a widespread wall thinning" of left ventricle with apical perfusion defect. Simultaneous electrocardiogram showed further ST depression and the patient had chest pain. In 6 months after aortic valve replacement the patient no longer demonstrated both apical perfusion defect and "wall thinning" in postoperative thallium-201 myocardial SPECT images and also had neither ST depression nor chest pain. Thus; a transient "dilation and wall thinning" of left ventricle in this patient is suspected to be a sign of diffuse subendocardial ischemia.

[The clinical significance of reverse redistribution of Tl-201 SPECT at rest in the 1st month after the onset of acute myocardial infarction].

The pattern of Thallium-201 reverse redistribution (r-RD) at rest has been reported in some patients with acute myocardial infarction (AMI) in the acute phase. But there is no report of this pattern in the later phase. To investigate the significance of Thallium-201 reverse redistribution in the subacute phase, 37 patients with AMI underwent Thallium-201 SPECT at rest a month after the onset. The patients were classified into three groups visually and 19 of 37 patients (51%) showed the persistent defect pattern (Group PD), and the remaining 18 patients (49%) had the reverse redistribution pattern (Group r-RD). None of them had the redistribution pattern. Coronary reflow was earlier and the incidence of the scintigraphic overlap on Dual SPECT image of 99mTc-PYP/201TlCl in the acute phase was more frequent in Group r-RD than in Group PD. A decrease in thallium defect size of patients with r-RD from the acute phase to one month after the onset represented improvement more significantly than that with PD. Initial %Tl uptake of the infarcted region of Group r-RD was greater than that of Group PD. The degree of stenosis of the infarct-related coronary artery in Group r-RD was less severe than that in Group PD. And corresponding regional wall motion of Group r-RD was less impaired. The Thallium-201 washout in the infarcted region with r-RD was significantly faster than that in the normal region. It is concluded that the r-RD pattern at rest in the 1st month after the onset of AMI may be a sign of viable myocardium.