Protein kinase A activators inhibit agonist induced prostaglandin production in human amnion

Prostaglandin (PG) production by human amnion has been postulated to have a role in the onset of labor. Previous work by ourselves and others has demonstrated that oxytocin, phorbol esters and epidermal growth factor (EGF) increase PGE2 production in human amnion cells by activation of the Phospholipase C/Protein Kinase C (PKC) cascade system. The present study was undertaken to determine the effect of prior activation of the Adenylate Cyclase cascade system upon subsequent stimulation of PGE2 production by oxytocin, phorbol 12-myristate-13-acetate (PMA) or EGF in amnion cells and membrane discs. Isoproterenol, forskolin and dibutyryl cyclic adenosine monophosphate (dbcAMP) were utilized to activate the Adenylate Cyclase system at the receptor, enzyme and second messenger level. In control amnion cells, oxytocin, PMA and EGF each provoked dose dependent increases in PGE2 production. In cells preincubated with dbcAMP, forskolin or isoproterenol, agonist stimulated PGE2 production was markedly (50-90%) inhibited (p < 0.01). Inhibition was dose dependent upon preincubator concentrations. Maximal inhibition by adenylate cyclase activators occurred with 2-4 h of preincubation. In membrane discs, forskolin preincubation also inhibited oxytocin, PMA and EGF stimulation of PGE2 production. Activation of the Adenylate Cyclase system in human amnion cells or membrane discs inhibits the subsequent action of potent stimulators of PGE2 production in human amnion.     

Exercise training alters endothelium-dependent vasoreactivity of rat abdominal aorta

We tested the hypothesis that adaptations in peripheral arterial vasoreactivity are induced by exercise training. Male rats were trained to run on a treadmill at 30 m/min (15 degrees incline) for 1 h/day 5 days/wk for 10-12 wk. Efficacy was indicated by a 51% increase (P < 0.05) in citrate synthase activity in soleus muscle of exercise-trained (ET) rats compared with that of sedentary (SED) control rats. Responses to vasoactive compounds were examined in vitro using rings of abdominal aorta. Maximal isometric contractile tension evoked by KCl, norepinephrine (NE), and phenylephrine were not different between groups; sensitivity to phenylephrine was also not different between groups. However, sensitivity was lower for both KCl and NE in vessels from ET animals. Endothelium removal did not influence KCl sensitivity but did abolish the difference in NE sensitivity of vessel segments between ET and SED animals. Maximal vasodilator responses induced by acetylcholine (ACh; NE or prostaglandin F2 alpha preconstriction) were greater in vessel rings from ET rats. However, dilatory responses by sodium nitroprusside (NE or prostaglandin F2 alpha preconstriction) and forskolin (NE preconstriction) were not different between groups, indicating that the augmented ACh-induced dilatory response resulted from an adaptation of the endothelium. Blockade of nitric oxide synthase activity diminished ACh-induced vasodilation by 79 and 100% in SED and ET rats, respectively. These results indicate that training alters vasomotor function in rat abdominal aortas through adaptations of both endothelium and smooth muscle.     

Asbestos-related pericardial thickening detected by magnetic resonance imaging

Magnetic resonance imaging was performed in four male asbestos workers in whom the chest radiograph revealed pleural but not pulmonary or pericardial disease. Patients underwent thoracic multislice spin echo imaging, with measurement of left and right ventricular volumes at end-diastole and end-systole, and a study of the flow in the superior vena cava as an indirect measure to the filling of the right ventricle. Patients also underwent respiratory function tests and high-resolution computed tomography (HRCT). Magnetic resonance, but not HRCT, showed pericardial thickening in two patients. Magnetic resonance demonstrated reduced diastolic flow in the superior vena cava in one patient, reflecting impaired right ventricular filling. All other magnetic resonance measurements of cardiac function were normal. HRCT demonstrated mild asbestosis in three patients in which neither the chest radiograph nor magnetic resonance showed signs of parenchymal disease, and pericardiac calcification without thickening in one patient. It is concluded that magnetic resonance is superior to HRCT in identifying pericardial thickening, but that HRCT is superior to magnetic resonance in identifying asbestos-related pleural and pulmonary disease.     

T cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis

To establish the relationships among T and B cell responses, active infection, and clinical manifestations in lymphatic filariasis, filarial-specific lymphocyte proliferation, IgG antibody isotypes, and IgE levels were determined in an exposed population: 31 asymptomatic amicrofilaremics, 43 microfilaremics, 12 symptomatic amicrofilaremics, and 52 elephantiasis patients. Lymphocyte proliferation was higher in elephantiasis patients and asymptomatic amicrofilaremics than in microfilaremics (P < .004). A proportion of asymptomatic amicrofilaremics (32%), elephantiasis patients (37%), and symptomatic amicrofilaremics (58%) showed antigen-specific lymphocyte unresponsiveness, and lymphocyte proliferation to filarial antigens correlated negatively with specific IgG4 levels (rho = -0.315, P < .001). As elevated specific IgG4 is an indicator of active infection, it is argued that active infection may result in lymphocyte hyporesponsiveness irrespective of clinical category. Of those with elevated specific IgE levels and high T cell proliferative responses, 70% had elephantiasis, suggesting these factors have a role in pathology. However, the existence of a proportion of elephantiasis patients with low anti-filarial IgE and T cell unresponsiveness to filarial antigens suggests that elephantiasis can be caused by distinct processes.     

Adapting to supernormal auditory localization cues. I. Bias and resolution

Head-related transfer functions (HRTFs) were used to create spatialized stimuli for presentation through earphones. Subjects performed forced-choice, identification tests during which allowed response directions were indicated visually. In each experimental session, subjects were first presented with auditory stimuli in which the stimulus HRTFs corresponded to the allowed response directions. The correspondence between the HRTFs used to generate the stimuli and the directions was then changed so that response directions no longer corresponded to the HRTFs in the natural way. Feedback was used to train subjects as to which spatial cues corresponded to which of the allowed responses. Finally, the normal correspondence between direction and HRTFs was reinstated. This basic experimental paradigm was used to explore the effects of the type of feedback provided, the complexity of the stimulated acoustic scene, the number of allowed response positions, and the magnitude of the HRTF transformation subjects had to learn. Data showed that (1) although subjects may not adapt completely to a new relationship between physical stimuli and direction, response bias decreases substantially with training, and (2) the ability to resolve different HRTFs depends both on the stimuli presented and on the state of adaptation of the subject.     

Generation of chromosome fragment specific bovine DNA sequences by microdissection and DOP-PCR

Trends in causative organisms and sources of infection were studied in a series of 288 episodes of bacteremia in neutropenic cancer patients observed in a single institution from 1986 to 1993. The incidence of bacteremia increased significantly from 20 episodes per 1000 admissions in 1986 to 50 episodes per 1000 admissions in 1993 (p = 0.00001). Over the study period, a continuous increment in gram-positive bacteremia, which reached 81% of episodes in 1993 (p = 0.000001), was observed. Conversely, the incidence of gram-negative bacteremia remained stable. Coagulase-negative staphylococci and viridans group streptococci were the most commonly isolated pathogens. Bacteremia caused by coagulase-negative staphylococci increased from 3 episodes per 1000 admissions to 19 episodes per 1000 admissions (p = 0.0001), and viridans group streptococci bacteremia increased from 0 episodes per 1000 admissions to 19 episodes per 1000 admissions (p = 0.000001). The upward trend in gram-positive bacteremia appeared to be related to a significant increase in both intravascular catheters (p = 0.003) and oral mucositis (p = 0.003) as sources of infection. Specific strategies to prevent chemotherapy-induced mucositis and catheter-related bacteremia merit further investigations.     

c-KIT expression enhances the leukemogenic potential of 32D cells

The growth of human leukemic cells in culture and in vivo is dependent upon the presence of hematopoietic growth factors. Most populations of human leukemic acute myeloblastic leukemia (AML) cells express c-Kit on their surface and respond to Kit ligand (KL) in culture. To determine if this interaction was of potential significance in vivo we used a mouse model system. 32D cells, a murine IL-3-dependent myeloid cell line, were rendered KL responsive by transfection of the murine c-Kit. After injection of 32D or 32D-Kit cells into syngeneic hosts, animals bearing 32D-Kit cells, but not 32D cells, became moribund and were killed. These animals had circulating leukemic blast cells, infiltration of bone marrow, spleen, brain, liver, lung, and kidney. Cells recovered from some of the animals continued to be dependent upon IL-3 or KL for growth while in other cases the cells were factor independent. This model illustrates that the constitutive expression of c-Kit enhances the leukemic potential of 32D cells. The model will be useful for studying the progression of leukemia in vivo and testing whether interruption of the interaction of Kit and KL can affect the growth of leukemic cells.     

Stimulation of monocyte tissue factor expression in an in vitro model of bacterial endocarditis

The coagulation system plays a major role in the formation of the infected endocardial vegetation in bacterial endocarditis. Since monocytes can express tissue factor (TF) on their surfaces, they are thought to be responsible for the extrinsic activation of the coagulation cascade during this disease. The present study used an in vitro model in which fibrin plates, isolated adherent monocytes, and Streptococcus sanguis were used as an analog for endocardial vegetations. Adherence to fibrin by itself was found to stimulate TF expression on the monocytes, but stimulation by S. sanguis significantly increased TF expression, which was found to be maximal at a bacterium-to-monocyte ratio of 9 or more.     

Intestinal metaplasia with adherent Helicobacter pylori: a hybrid epithelium with both gastric and intestinal features

Helicobacter pylori seem to avoid areas of intestinal metaplasia in the gastric mucosa, but attachment of these bacteria to epithelium with the appearance of incomplete intestinal metaplasia has been documented. To characterize the nature of the epithelium to which H pylori was attached, we carried out an immunohistochemical study using monoclonal antibodies against gastric surface mucous cell mucins (M1), blood group-related carbohydrates antigens (Le(a), sialyl Le(a), Le(b), type 1H, and type 2H) and sialyl Tn antigen. The results of this study suggest that these areas of H pylori attachment represent a hybrid epithelium whose cells share characteristics of both gastric surface mucous cells and intestinal metaplastic cells. Whether all areas of incomplete intestinal metaplasia represent an intermediate stage between the normal gastric epithelium and the fully developed complete type of metaplasia remains to be determined.