Mass contents of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol in human platelets stimulated with a thromboxane analogue and thrombin.

Mass contents of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DG) were measured in U46619-stimulated human platelets. 1 microM of U46619 induced maximum responses in aggregation, 5-hydroxytryptamine (5HT) secretion and increase in intracellular free Ca2+ concentration ([Ca2+]i). Aggregation was almost comparable to that induced by maximal dose (1 U/ml) of thrombin, while 5HT release was almost half. The initial [Ca2+]i peak in response to U46619 was about half of thrombin stimulation. Production of IP3 and DG was, however, less than one tenth of that seen in thrombin stimulation. The profile (time course and concentration-dependency) of IP3 formation did not correlate with that of [Ca2+]i, suggesting that U46619 stimulates IP3-dependent and -independent Ca2+ mobilization. DG production was small but sustained for more than 5 min. These findings support the recent hypothesis that aggregation is regulated by a delayed accumulation of DG. The low level of 5HT secretion could be explained by the low production of second messengers, IP3 and DG.     

Increased matrix metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue

Ovarian cancer cells disseminate by attachment to the peritoneal mesothelial cell surface of the abdominal cavity. We therefore investigated the influence of conditioned medium (CM) from human peritoneal tissues and mesothelial cells on the secretion of matrix metalloproteinases (MMPs) by ovarian cancer cells. The molecular weights of MMPs stimulating factors derived from human peritoneal tissues and mesothelial cells were estimated using microconcentrators with various cut-off membranes. Human peritoneal tissues were obtained from 12 surgical patients, and mesothelial cells were isolated from three peritoneal specimens. Exposure to CM from peritoneal tissue caused a concentration-dependent increase of the MMP-2 and MMP-9 bands in CM from NOM1 ovarian cancer cells, as shown by zymography. There was a significant difference in the increase of MMP-2 and MMP-9 (2.46-fold and 7.14-fold, respectively, at 0.4mg/ml protein; P < 0.005). CM from mesothelial cells also significantly increased the secretion of MMP-9 by NOM1 cells. The molecular size of possible MMP-9-stimulating factors secreted by peritoneal tissues and mesothelial cells was above M 100000. Further, CM of peritoneal tissues and mesothelial cells also induced the invasiveness of NOM1 cells. These findings suggest that mesothelial cells may secrete some factors which predominantly induce the MMP-9 production and increase invading cell numbers.     

The effect of a specific thromboxane A2 antagonist, AA-2414 on airway hyperresponsiveness induced by ozone exposure in dogs]

To determine whether thromboxane A2 (TxA2) is involved in airway hyperresponsiveness induced by ozone exposure, we studied the effect of a specific TxA2 antagonist, AA-2414 on ozone-induced airway hyperresponsiveness in seven dogs. Airway responsiveness to inhaled methacholine was determined by modified Astograph (7 Hz oscillation method), and numbers of neutrophils in the peripheral blood, neutrophil counts in bronchoalveolar lavage fluid (BALF), the levels of TxB2 and 6-keto-Prostaglandin F1 alpha (6-keto-PGF1 alpha) in BALF were measured before and after ozone exposure, and after ozone exposure with pretreated AA-2414. Ozone exposure was carried out for 2 hr at an ozone level of 3.06 +/- 0.06 ppm (mean +/- SE). Airway responsiveness to inhaled methacholine increased significantly after ozone exposure (p less than 0.01), and the hyperresponsiveness induced by ozone exposure was inhibited significantly by pretreated AA-2414 (p less than 0.01). Numbers of neutrophils in the peripheral blood and neutrophil counts in BALF increased after ozone exposure, and these increase were not inhibited by pretreated AA-2414. There was no apparent change in the levels of TxB2 in BALF after ozone exposure and after ozone exposure with pretreated AA-2414, however the levels of 6-keto-PGF1 alpha in BALF decreased after ozone exposure and after ozone exposure with pretreated AA-2414 (p less than 0.1). These results suggest that TxA2 plays an important role in the development of airway responsiveness after ozone exposure in dogs, and ozone-induced airway hyperresponsiveness may not be associated with the hyperproduction of TxA2 but with the relative increase of TxA2 due to the decrease of PGI2.     

Ontogeny of plasma cells in the early rat yolk sac

The present study investigated the development of plasma cells in the early rat yolk sac (days 10-16 of gestation) by light microscopy, transmission electron microscopy, immunoelectron microscopy, and indirect immunofluoresce techniques. Cells delineating the morphology of plasma cells in the yolk sac were observed as early as 12 days of embryonic life. As for positive immune staining for the intra-cytoplasmic immunoglobulin (Ig) production (IgA, IgM and IgG), the intensity of the immune staining was very weak on days 10 and 11 of gestation, while it turned very dense on day 12 of gestation. At 14 days of gestation, the number of positive cells was markedly reduced. Immunoelectron microscopy visualized products of the immune reaction in cisterns of the rough endoplasmic reticulum. Conventional electron microscopic examination of 12, 13, and 16-day yolk sacs confirmed the development and differentiation of plasma cells with their well-known ultrastructural features, making this the first study to demonstrate these in the early rat yolk sac. The development of plasma cells in the early yolk sac implies the ability of the yolk sac to effect a humoral immune response at this stage of fetal life. The probable role of plasma cells in the yolk sac is also discussed.     

The effect of AH 21-132 on airway hyperresponsiveness induced by ozone exposure

We examined the effect of AH 21-132, which has been reported to relax airway smooth muscle and inhibit platelet activating factor (PAF)-induced airway hyperreactivity, on ozone-induced airway hyperresponsiveness (AHR) with airway inflammation in dogs. Airway responsiveness (AR) to methacholine was measured by modified Astograph (7 Hz oscillation method) before and after ozone exposure, and the numbers of neutrophils in the peripheral blood and total cell counts, differential cell counts and TXB2 in BALF were measured before and after ozone exposure. Ozone exposure was carried out for 2 hr at an ozone level of 3.46 +/- 0.10 ppm (mean +/- SE). There was a significant increase in AR to methacholine after ozone exposure (p less than 0.01), and the numbers of neutrophils in the peripheral blood and the total cell and neutrophil counts in BALF increased significantly (p less than 0.05). Pretreatment with AH 21-132 at an oral dose of 20 mg/kg significantly prevented the ozone-induced AHR to methacholine (p less than 0.01), and also inhibited the increase of neutrophil counts in the peripheral blood, and the total cell counts and the neutrophil counts in BALF after ozone exposure. There was no significant change in the levels of TXB2 in BALF before and after ozone exposure. In dogs not exposed to ozone, AR to methacholine and respiratory resistance to methacholine significantly decreased after administration of AH 21-132 at an oral dose of 20 mg/kg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Chylothorax as the initial manifestation of malignant pleural mesothelioma--a case report]

A case of chylothorax associated with diffuse malignant pleural mesothelioma in a 53-year-old woman was reported. Chest radiography in a mass examination revealed right pleural effusion. A thoracentesis yielded fluid with characteristics consistent with chyle. In spite of our suggestion that thoracoscopy for further examination was necessary, the patient and her husband had refused the operation for months. Chest CT scanning revealed a nodule behind the xiphoid process. Lymphoscintigraphy suggested an obstruction of the right parasternal lymphatic vessel. Repeated thoracentesis did not yield a diagnosis. As bilateral pleural effusion and chylous ascites appeared, dyspnea worsened. About 2 years after the mass examination thoracoscopy was performed. On thoracoscopic exploration, a nodule was found in the anterior mediastinum and a biopsy was performed. Histological analysis revealed that the patient had the epithelial subtype of malignant pleural mesothelioma. Thoracoscopic pleural biopsy is a useful means of establishing the nature of a chylous effusion. In adult patients with chylothorax, thoracoscopic exploration should be performed as soon as possible to rule out malignancy.     

Tumor promoting activity of teleocidin in skin and forestomach of mice initiated transplacentally with 7,12-dimethylbenz(a)anthracene

Summary Experiments on the effect of transplacental initiation with 7,12-dimethylbenz(a)anthracene (DMBA) and postnatal promotion with teleocidin were carried out in mice. The percentage of tumorbearing mice among females treated with DMBA transplacentally on day 17 of gestation and postnatally by topical application of teleocidin to the skin of the back was 73.3% in week 30, whereas that among females treated with DMBA on day 10 of gestation and postnatally by topical application of teleocidin was 20.0%. This indicates that teleocidin shows potent tumor promoting activity on mouse skin in a transplacental initiation and postnatal promotion protocol.Furthermore, in the males treated with DMBA transplacentally on day 17 of gestation and given diet containing 0.01% teleocidin postnatally five tumors of the forestomach were found in 5 of 19 effective mice (26.3%) in week 52. One of these five tumors was a squamous cell carcinoma, and the others were papillomas. This indicates that teleocodin also has tumor promoting activity in the forestomach of mice.Dedicated to Professor Erich Hecker on the occasion of his 60th birthday     

Efficacy,safety, and pharmacokinetics of oral valganciclovir in patients with congenital cytomegalovirus infection

ObjectivesValganciclovir (VGCV) has been shown to improve sensorineural hearing loss (SNHL) and neurological outcomes in patients with neonatal symptomatic congenital cytomegalovirus (cCMV) infection. However, reports on the pharmacokinetics, efficacy and safety of oral VGCV are limited. The aim of this study is to evaluate the pharmacokinetics of VGCV for use in the treatment of cCMV.MethodsThis was a single-center, retrospective observational study conducted at Saitama Children's Medical Center in Japan between 2012 and 2017. CMV DNA copy number, maximum plasma VGCV concentration (Cmax), and adverse events (ADEs) during treatment were evaluated.ResultsA total of 26 patients with cCMV who received VGCV were included in this study. The median age at VGCV initiation was 9.5 months (range 0–46). Twenty-one patients (81%) had SNHL at baseline. Of these, five patients (19%) presented with improved SNHL, and none experienced worsened SNHL during treatment. The mean VGCV Cmax was 3.5 μg/mL (range 2–5.3), with no significant variation among individual values, and the values were maintained during treatment. Furthermore, there were no correlations between the Cmax values and age, sex, SNHL improvement or ADEs. Neutropenia (<1000/mm³) was observed in six patients (23%); however, no serious ADEs occurred.ConclusionsVGCV prevented the progression of SNHL without serious ADEs due to its stable pharmacokinetics. This study provides safety and tolerability of VGCV for the treatment of cCMV patients.     

Practice of universal precautions and risk of occupational blood-borne viral infection among Congolese health care workers

The extent of occupational injuries among health care workers in central Africa, particularly in the Democratic Republic of Congo, is not documented. We sought to determine the incidence of percutaneous injury and exposure to blood and other body fluids in Congolese urban and rural hospitals in the previous year. Our data show high rates of percutaneous injury and exposure to blood and other body fluids, reflecting poor safety conditions for most Congolese health care workers.