Plasminogen activator inhibitor types 1 and 2 in human trophoblasts. PAI-1 is an immunocytochemical marker of invading trophoblasts

Trophoblast implantation, vascular remodeling, and maintenance of intervillous blood flow may depend on the regulated production of proteolytic enzymes such as plasminogen activator (PA). Since the functional activity of plasminogen activators is determined not only by the quantity of protease but also by levels of specific plasminogen activator inhibitors (PAI), we examined trophoblasts both in vitro and in vivo for the presence of two PAIs, PAI-1 and PAI-2. Cytotrophoblasts were isolated from first trimester or term placentae, cultured, and immunocytochemically stained using specific anti-PAI antibodies. The antiserum against PAI-1 demonstrated prominent cell-surface staining and some cytoplasmic staining. The antiserum generated against PAI-2 revealed a cytoplasmic localization, with some trophoblasts staining intensely, whereas others had no apparent reactivity. We also found that cultured cytotrophoblasts contain the mRNAs for PAI-1 and PAI-2. Immunohistochemical analysis of tissue sections from 8-, 16-, and 40-week implantation sites using antisera against PAI-1 demonstrated weak staining of villous syncytiotrophoblasts but prominent cytoplasmic staining of trophoblasts invading the decidua and myometrium. Antisera against PAI-2 stained the cytoplasm of villous syncytiotrophoblasts, but no staining was evident in villous cytotrophoblasts or in invading trophoblasts. We conclude that 1) human trophoblasts can express both PAI-1 and PAI-2 in vitro and in vivo and 2) prominent PAI-1 immunostaining defines invading trophoblasts, whereas PAI-2 is the predominant PAI accumulated in villous syncytiotrophoblasts. Thus, the various trophoblast forms have distinctive patterns of PAI expression.     

Rapid detection of bacterial growth in blood samples by a continuous-monitoring electrical impedance apparatus.

A growth detection method utilizing an automated apparatus capable of rapidly detecting bacterial growth by measuring changes of electrical impedance in bacteriological medium was utilized with "mock" blood cultures containing various gram-negative and gram-positive bacteria. Measurement of changes of electrical impedance was found to ba as accurate and comparable for time of growth detection as the radiometric method for detection of the same bacteria using mock blood cultures. In a limited clinical trial the use of the electrical impedance apparatus detected in 1 positive specimen from 40 clinical blood specimens as rapidly as by radiometric measurement. Both methods were considerably faster for detecting bacterial growth as compared with conventional culture methods. The selected species of gram-positive and -negative organisms tested were all detected by the electrical impedance method, including aerobes and anerobes. However, addition of 5% CO2 to the incubation atmosphere enhanced detection of gram-positive organisms.     

Effects of N-methyl-D-aspartate-induced amygdala lesion in rats submitted to the elevated T-maze test of anxiety

The elevated T-maze (ETM) has been used to generate two defensive behaviors in the same rat, inhibitory avoidance and one-way escape, which have been related to generalized anxiety and panic, respectively. In the present study, we investigate the role of the amygdala on the modulation of these two behaviors. Male Wistar rats were tested in the ETM test 2, 7, or 14 days after bilateral N-methyl-D-aspartate (NMDA)-induced lesion of the amygdala. The animals were also tested in an open field for evaluation of motor performance. The results showed that animals tested 7 days after NMDA injection had impairment in the acquisition of inhibitory avoidance, indicating an anxiolytic effect. Lesion of the amygdala did not change one-way escape in any of the tested groups. These results provide further evidence for the involvement of the amygdala in the modulation of defensive behaviors that have been associated to generalized anxiety.     

Effects of cyclosporin A on experimental infection with Listeria monocytogenes.

The effects of cyclosporin A on primary and secondary infection of mice with Listeria monocytogenes was studied both at the microbiological and the histomorphological level. This drug, when given in a dose of 100 mg/kg/day, was found to inhibit the development of protective immunity after primary infection as well as the expression of acquired immunity to challenge infection as determined by counting of bacterial numbers in the spleen. The manifestation of delayed type hypersensitivity was also impaired. When the cellular immune system was functionally intact, the formation of granulomas composed of macrophages and lymphocytes enabled the animals to overcome the Listeria infection. In mice treated with cyclosporin A protective granulomatous reaction during secondary infection did not occur. Instead numerous necropurulent lesions developed in the reticuloendothelial organs, such as spleen and liver, of animals unable to control the lethal infection.     

Type I glutaric aciduria,part 1: natural history of 77 patients

Type I glutaric aciduria (GA1) results from mitochondrial matrix flavoprotein glutaryl-CoA dehydrogenase deficiency and is a cause of acute striatal necrosis in infancy. We present detailed clinical, neuroradiologic, molecular, biochemical, and functional data on 77 patients with GA1 representative of a 14-year clinical experience. Microencephalic macrocephaly at birth is the earliest sign of GA1 and is associated with stretched bridging veins that can be a cause of subdural hematoma and acute retinal hemorrhage. Acute striatal necrosis during infancy is the principal cause of morbidity and mortality and leads to chronic oromotor, gastroesophageal, skeletal, and respiratory complications of dystonia. Injury to the putamen is heralded by abrupt-onset behavioral arrest. Tissue degeneration is stroke-like in pace, radiologic appearance, and irreversibility. It is uniformly symmetric, regionally selective, confined to children under 18 months of age, and occurs almost always during an infectious illness. Our knowledge of disease mechanisms, though incomplete, is sufficient to allow a rational approach to management of encephalopathic crises. Screening of asymptomatic newborns with GA1 followed by thoughtful prospective care reduces the incidence of radiologically and clinically evident basal ganglia injury from approximately 90% to 35%. Uninjured children have good developmental outcomes and thrive within Amish and non-Amish communities.     

Mutants of sindbis virus. I. Isolation and partial characterization of 89 new temperature-sensitive mutants.

More than 100 new temperature-sensitive mutants of Sindbis virus have been isolated, following mutagenesis with nitrous acid, N-methyl-N′-nitro-N-nitrosoguanidine, 5-azacytidine, and 5-fluorouridine. Thirty-six of these mutants synthesize at least 60% as much RNA at the nonpermissive temperature as does the parental strain and are designated RNA⁺; 23 mutants synthesize between 10 and 60% as much RNA as the parental strain at 40° and are designated RNA^±; 30 mutants make less than 10% as much RNA at 40° and are called RNA^?. The remaining mutants have not been tested for RNA incorporation.The thermal stability at 56° of most of the mutant particles has been examined. The majority of the RNA⁺ mutants is more sensitive to heating at 56° than the parental HR strain, and RNA⁺ mutations appear to reside primarily in genes coding for the structural proteins. Approximately 20% of either RNA^± or RNA^? mutants are thermosensitive, and these mutations thus appear to reside primarily in genes coding for the nonstructural proteins.Complementation assays have been performed with a number of these mutants and with those of Burge and Pfefferkorn (1966a, b). The existence of three complementation groups among the RNA⁺ mutants, which appear to encode the three major structural proteins, has been confirmed; no new complementation groups among RNA⁺ mutants have been identified. A total of four complementation groups has been identified among the RNA^? mutants. Thus, Sindbis virus contains at least seven complementation groups.     

Verletzungen und gewaltsamer Tod aus physikalischer Ursache

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