Inactivation of human tumor cell pro-urokinase by granulocyte elastase

Supernatant obtained from granulocytes stimulated in the presence of cytochalasin B by the chemotactic peptide N-formyl-norleucyl-leucyl-phenylalanyl-norleucyl-tyrosyl- lysine displayed an inhibitory effect on the plasmin-dependent conversion of tumor urokinase-type plasminogen activator proenzyme (pro-uPA) to the active form of uPA. Moreover, the supernatant was also found to inhibit the fibrinolytic activity of human vulva (A431) and breast (MCF7) carcinoma cell lines, which contain large amounts of pro-uPA, by 87% and 96%, respectively. By using eglin C (elastase inhibitor) and a monoclonal antibody to elastase (proteolytic activity blocker of the enzyme), elastase was identified as the key enzyme of the supernatant in these phenomena. Purified elastase converted pro-uPA to an enzymatically inactive molecule composed of two polypeptide chains of Mr = 33,000 and 22,000 linked to each other by a disulfide bond. Elastase-containing granulocytes were identified by immunohistochemistry techniques in the tissues of squamous cell carcinoma and adenocarcinoma of uterus. The cells were found close to the tumor cells and in the stroma surrounding the tumor nests. By immunohistochemical staining, uPA was also found in the tumor cells. Evidently, elastase released by chemotactically activated granulocytes, which are attracted into tumor tissues, may inhibit the conversion of pro-uPA to enzymatically active uPA in the tumor cells.     

Two cases of lymphocytic infundibuloneurohypophysitis

We report two cases of lymphocytic infundibuloneurohypophysitis (LIH). A 32-year-old male and a 13-year-old male were admitted to our hospital because of a sudden occurrence of the diabetes insipidus (DI). MRI of both patients showed the disappearance of hyperintensity of the posterior pituitary in T1WI, pituitary stalk swelling and enlargement of the pituitary gland, with homogeneous enhancement by gadolinium. We thereby diagnosed LIH, so neither patient was operated on, but both were followed-up conservatively. We reviewed 51 cases of LIH. The patient's ages ranged from 4 to 74 years (mean 45.4 years). Based on the initial symptoms, DI was found in all cases. Almost all these cases revealed characteristic MRI findings similar to those in our cases. The mean follow-up period was 3.1 years. The rate of disappearance of radiological abnormalities was 56.2%, but only 13.7% of DI improved. If we encounter a patient presenting with idiopathic DI whose MRI is strongly suggestive of LIH, and barring the necessity of an urgent operation, careful conservative treatment is advised.     

Engraftment and tumor formation after allogeneic in utero transplantation of primate embryonic stem cells

BACKGROUND: To achieve human embryonic stem (ES) cell-based transplantation therapies, allogeneic transplantation models of nonhuman primates would be useful. We have prepared cynomolgus ES cells genetically marked with the green fluorescent protein (GFP). The cells were transplanted into the allogeneic fetus, taking advantage of the fact that the fetus is so immunologically immature as not to induce immune responses to transplanted cells and that fetal tissue compartments are rapidly expanding and thus providing space for the engraftment. METHODS: Cynomolgus ES cells were genetically modified to express the GFP gene using a simian immunodeficiency viral vector or electroporation. These cells were transplanted in utero with ultrasound guidance into the cynomolgus fetus in the abdominal cavity (n=2) or liver (n=2) at the end of the first trimester. Three fetuses were delivered 1 month after transplantation, and the other, 3 months after transplantation. Fetal tissues were examined for transplanted cell progeny by quantitative polymerase chain reaction and in situ polymerase chain reaction of the GFP sequence. RESULTS: A fluorescent tumor, obviously derived from transplanted ES cells, was found in the thoracic cavity at 3 months after transplantation in one fetus. However, transplanted cell progeny were also detected (approximately 1%) without teratomas in multiple fetal tissues. The cells were solitary and indistinguishable from surrounding host cells. CONCLUSIONS: Transplanted cynomolgus ES cells can be engrafted in allogeneic fetuses. The cells will, however, form a tumor if they "leak" into an improper space such as the thoracic cavity.     

Evaluation of extracranial-intracranial arterial bypass function by using near-infrared spectroscopy

OBJECT: It has been reported that extracranial-intracranial (EC-IC) arterial bypass surgery can be useful in preventing stroke in patients with hemodynamic compromise. Little is yet known, however, regarding the extent to which the bypass contributes to maintaining adequate cerebral blood oxygenation (CBO) and its temporal changes following surgery. The authors evaluated bypass function repeatedly by using near-infrared spectroscopy (NIRS) after surgery. METHODS: The authors investigated 30 patients who had undergone EC-IC bypass surgery. Single-photon emission computerized tomography revealed a decrease in regional cerebral blood flow (rCBF) and a lowered rCBF response to acetazolamide. Changes in CBO were evaluated in the sensorimotor cortex during compression of the anastomosed superficial temporal artery (STA). When decreases in oxyhemoglobin (HbO2) and total hemoglobin (Hb) concentrations were observed, the bypass was considered to have maintained CBO in the sensorimotor cortex given that decreases in HbO2 and total Hb indicate cerebral ischemic changes. The bypass maintained CBO immediately after surgery in 36.7% of patients (Group I, 11 patients) and at some time after surgery, mostly within 1 year, in 43.3% of patients (Group II, 13 patients); however, it did not maintain it throughout the follow-up period in 20% of patients (Group III, six patients). Note that the preoperative rCBF in patients in Groups I and II was lower than that in patients in Group III (p < 0.004). In fact, the preoperative rCBF predicted whether a bypass would maintain CBO at a cutoff value of 24.5 to 25 ml/100 g/min. Among Groups I and II, 18 patients demonstrated an increase in deoxyhemoglobin during STA compression. The preoperative rCBF in these cases was lower than that in the six remaining patients (p < 0.006). Note that the preoperative rCBF predicted the postoperative deoxyhemoglobin response at a cutoff value of 22.2 to 24 ml/100 g/min. CONCLUSIONS: The EC-IC bypass surgery can maintain CBO immediately after surgery or gradually within 1 year when the preoperative rCBF is below 24.5 to 25 ml/100 g/min. Furthermore, bypass flow plays a critical role in maintaining an adequate CBO when preoperative rCBF is below 22.2 to 24 ml/100 g/min.     

Hemorrhagic complication of stereotactic surgery in patients with movement disorders

OBJECT: Small, asymptomatic hemorrhages are easier to detect during stereotactic surgery when magnetic resonance (MR) imaging is used for targeting rather than when traditional approaches, such as ventriculography, are performed with contrast material. In the present study the authors examined the actual incidence of intraoperative hemorrhages in patients with movement disorders who had undergone MR imaging-targeted surgery, microelectrode recording (MER)-guided implantation of deep brain stimulation (DBS) electrodes, or radiofrequency-induced coagulation surgery performed. METHODS: Ninety-six consecutive patients underwent a total of 116 stereotactic operations for movement disorders (57 operations for radiofrequency-induced coagulation and 59 for DBS electrode implantation) between January 1998 and November 2002. The authors investigated the correlation between hemorrhages and other factors including the location of the hemorrhage and the type of surgery performed. Postoperative computerized tomography scans demonstrated the occurrence of intraoperative hemorrhages at 12 locations during 11 procedures (9.5% of all procedures). Nine hemorrhages occurred during 57 coagulation operations (15.8%). Within this group, the frequency of hemorrhages was highest during thalamotomy (five [21.7%] of 23 procedures) and lower during pallidotomy (four [11.8%] of 34 procedures). In contrast, only two intraventricular hemorrhages developed during 59 operations in which DBS electrodes were implanted (3.4%). In no case was hemorrhage detected in the main DBS target, that is, the subthalamic nucleus. CONCLUSIONS: When small, asymptomatic hemorrhages were included in the estimation, the actual rate of hemorrhage was higher than that previously reported. Judging from the incidence of hemorrhage during coagulation and DBS surgeries, the authors suggest that the heat induced by coagulation may play a larger role than microelectrode penetration in the development of hemorrhage.     

Tubo-ovarian abscess occurring 16 years after supracervical hysterectomy

BACKGROUND: Supracervical hysterectomy is seldom performed and there are few reports of tubo-ovarian abscess (TOA) after supracervical hysterectomy. CASE: The case of a 49-year-old woman with a right TOA is reported. This patient had received a supracervical hysterectomy 16 years earlier due to rupture of the uterus. At this admission, she presented with complaints of, lower abdominal pain and fever. Bimanual and transvaginal ultrasound examinations demonstrated a tender mass in the right adnexal region. Laparotomy, pathologic examination and microbiologic study confirmed the diagnosis of right TOA. CONCLUSION: After supracervical hysterectomy, patients may develop endocervicitis, parametritis and/or TOA. This series may be a subtype of ascending infections in the female genital tract.