Arterial thrombosis model with photochemical reaction in guinea-pig and its property.

We have already developed an arterial thrombosis model in the rat femoral artery which utilized photochemical reaction between systemically injected rose bengal and transillumination of a green light with 540 nm wave length from the outside of the vessel. In the present study, we applied this model to guinea-pigs in order to produce a more suitable thrombus model for evaluation of antithrombotic drugs which act on the prostaglandin cascade. In the guinea-pigs, the irradiated femoral artery was completely occluded in 7 min after the injection of rose bengal (10 mg/kg) in a similar manner to the rats. The processes of primary endothelial injury and the subsequent formation of thrombus during this manipulation were observed by the electron microscopy. Pretreatment with aspirin and Y-20811, a thromboxane synthetase inhibitor, significantly prolonged the time required for occlusion in the guinea-pigs, while these drugs were ineffective in the rats. The antithrombotic effect of vapiprost, a thromboxane A2 receptor antagonist, was more pronounced in the guinea-pigs than the rats. In conclusion, this model in guinea-pigs is more suitable for evaluating antithrombotic drugs, particularly, the action of which is exerted involving the prostaglandin cascade.     

A case of progressive muscular dystrophy with numerous arterioluminal vessels

A 48-year-old man had histologically demonstrated cardiac involvement associated with progressive muscular dystrophy. On coronary arteriography, numerous vascular communications between the coronary arteries and the left ventricular chamber were found. These vascular communications are considered to be the arterioluminal vessels. This is the first report of a case of progressive muscular dystrophy with numerous arterioluminal vessels.     

Phase I study of cefixime, a new oral cephalosporin

The tolerance to and pharmacokinetics of cefixime, a new oral cephalosporin, were evaluated in healthy volunteers given the drug in single doses of 50, 100 and 200 mg and repeated doses of 200 mg bid for 14 days. In the repeated-dose study, there were mild and transient subjective symptoms such as soft stools, diarrhea, and anorexia, which disappeared without additional treatment during the dosing period. Slight increases in eosinophil and serum amylase levels were also observed. The serum concentrations of cefixime peaked at 0.71, 1.17, and 2.08 micrograms/mL on average, four to five hours after dosing with 50, 100, and 200 mg, respectively, and the half-lives were 2.54, 2.38, and 2.29 hours. Serum concentrations and urinary recoveries after dosing with 100 mg were little affected by food ingestion. There was no evidence of cefixime accumulation in the body by repeated dosing since mean serum concentrations and urinary recoveries were almost the same on the first, third, seventh, and 14th days of dosing.     

Facial nerve preservation in the region of the zygomatic arch

In order to preserve the frontotemporal branch of the facial nerve in frontotemporal and trans-zygomatic craniotomies, electromyographic responses from the facial muscles were recorded preoperatively. Incising the frontotemporal branch of the facial nerve could be avoided by identifying the crossing point of the frontotemporal branch of the facial nerve on the superior border of the zygomatic arch. The crossing points were investigated in 20 patients and in most cases they existed between 2 cm and 6 cm from the anterior border of the external auditory canal. Another important point to preserve the facial nerve is to conserve the layer in which the facial nerve is included. Therefore, the surgical anatomy in the region of the zygomatic arch and temporal area was reviewed in detail. This knowledge is crucial for neurosurgeons to dissect precisely in this region without causing postoperative facial palsy.     

Lattices of Type I Collagen Select Invasive Variants of K-ras Oncogene-Transfected NIH3T3 with Less Cellular fibronectin

A clone of NIH3T3 transformant (H3) can yield subcutaneous tumors and experimental pulmonary metastasis in nude mice. Compared to H3 in culture, the cells after in vivo tumor growth (H3-N) acquired enhanced tumorigenicity and metastatic ability. Also, indirect immunofluorescence revealed that cellular fibronectin (c-FN) of H3-N was decreased remarkably. We have studied the interactions between H3 and extracellular matrices to elucidate these phenomena. In the present study, we observed the effect of NIH3T3, H3, and H3-N cultured in type I collagen gel. Morphologically in the collagen gel, NIH3T3 assumed an extensive elongated fiber-like shape, H3 assumed a moderately elongated shape, and H3-N assumed a round or spindle shape with short pseudopodia. Compared to conventional cultures on dishes, cell proliferation of all three types was suppressed in collagen gel, but the degree of the suppression was least in H3-N. As a result, H3-N grew fastest in collagen gel. The variants which acquired growth advantage in the subcutaneum of mice also kept it in collagen gel. H3 cells were cultured in type I collagen gel for 4 weeks, a period comparable to that of tumor formation in nude mice. The cells after this long-term culture (H3-C) acquired enhanced tumorigenicity and metastatic ability nearly equal to that of H3-N. FACS analysis revealed that the c-FN of H3-C had decreased to a value comparable to that of H3-N. This means that type I collagen gel as well as subcutaneous tissues could select variants of H3 with less c-FN through proliferation. Moreover, it is suspected that lattices of type I collagen regulate cell proliferation of fibroblast via c-FN. This revised version was published online in August 2006 with corrections to the Cover Date.     

Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy

To investigate the possible role of the superoxide radical andits scavenging system in the human endometrium, the immunohistochemicaldistribution of superoxide dismutase (SOD), activities of SODand lipid peroxide concentrations were studied in the humanendometrium throughout the menstrual cycle and in early pregnancy.The endometrial epithelium showed a positive immunostainingfor Cu, Zn-SOD and Mn-SOD throughout the entire menstrual cycleand in early pregnancy. In the stroma, weak immunostaining forCu, Zn-SOD and moderate immunostaining for Mn-SOD were observedin the predecidual cells in the late secretory phase. Decidualcells in early pregnancy showed strong immunostaining for Cu,Zn-SOD and Mn-SOD. Total SOD activity in theendometrium increasedfrom early proliferative phase to mid-late proliferative phaseand further increased in the mid-secretory phase, and decreasedin the late secretory phase. The total SOD activity in the endometriumofearly pregnancy was the same level as that in the mid-secretoryphase. Cu, Zn-SOD and Mn-SOD activitieschanged in a similarmanner to total SOD activity throughout the menstrual cycleand in early pregnancy. Lipid peroxide concentration in theendometrium increased from early proliferative phase to mid-lateproliferativephase and further increased in the late secretoryphase. However, lipid peroxide concentration in theendometriumof early pregnancy was the same as that in the midsecretoryphase. These results suggested thatthe superoxide radical andits scavenging system may play an important role in the regulationof humanendometrial function.     

T cell can recognize the allospecificities formed by the substitution of amino acids associated with HLA-Bw4/Bw6 public epitopes.

Our previous studies clearly showed that HLA-B35 and HLA-Bw53 differed only by the amino acids associated with HLA-Bw4/Bw6 epitopes, in that the former possessed Bw6 and the latter Bw4 epitope. It remains to be known whether T cell can discriminate HLA-B35 from HLA-Bw53, although the difference between these HLA antigens is discriminated by monospecific human alloantisera. To investigate allorecognition of these HLA antigens by T cells, anti-HLA-Bw53 cytotoxic T lymphocytes (CTLs) were generated. Anti-HLA-Bw53 cytotoxic T lymphocytes (CTLs) were generated. Anti-HLA-Bw53 bulk CTLs from an individual with HLA-B35 clearly discriminated HLA-Bw53 from HLA-B35. On the other hand, anti-HLA-Bw53 bulk CTLs from an individual without HLA-B35 revealed weak cross-reactivity with HLA-B35 and HLA-B51. The additional studies using HLA-Bw53 or HLA-B35-specific CTL clones showed that some but not all of the CTL clones definitively distinguish the difference between HLA-Bw53 and HLA-B35. Thus, the allospecificities formed by HLA-Bw4/Bw6 epitopes were discriminated by allogeneic T cells. The present study demonstrated that HLA-Bw4/Bw6 public epitopes play an important role in allorecognition of T cells.     

Induction of superoxide dismutase by decidualization in human endometrial stromal cells

The present study was undertaken to investigate the effect of decidualization on superoxide dismutase (SOD) expression in human endometrial stromal cells (ESC). To induce decidualization, isolated ESC were incubated with medroxyprogesterone acetate (MPA, 10(-6) mol/l) and oestradiol (10(-8) mol/l) for 23 days. Insulin-like growth factor-binding protein-1 (IGFBP-1) was used as a marker of decidualization. SOD mRNA in ESC was significantly increased on day 12 of the hormone treatment (P < 0.01), which was concomitant with the onset of IGFBP-1 mRNA expression, and further increased until day 23 of the treatment in a manner similar to the change in IGFBP-1 expression. To examine the synergistic effect of human chorionic gonadotrophin (HCG) with MPA and oestradiol on SOD and IGFBP-1 expression, ESC were incubated with HCG in the presence or absence of MPA and oestradiol. HCG had no synergistic effect on SOD and IGFBP-1 expression. SOD activities in the decidualized endometrial tissue obtained from patients given oestradiol and progesterone for 7-10 days were significantly higher than those in the non-decidualized endometrial tissue from patients without the hormone treatment (P < 0.01). In conclusion, SOD expression in ESC was induced by MPA and oestradiol accompanied by decidualization, suggesting that SOD may play important roles in decidualization of ESC.