A molecular orbital theoretical study on the acid-base property and reactivity of the charge relay system in alpha chymotrypsin

The disintegration of the nuclear envelope has been examined in nuclei and nuclear envelopes isolated from amphibian oocytes from amphibian oocytes and rat liver tissue, using different electron microscope techniques (ultrathin sections and negatively or positively stained spread preparations). Various treatments were studied, including disruption by surface tension forces, very low salt concentrations, and nonionic detergents such as Triton C-100 and Nonidet P-40. The highest local stability of the cylinders of nonmembranous pore complex material is emphasized. As progressive disintegration occurred in the membrane regions, a network of fibrils became apparent which interconnects the pore complexes and is distinguished from the pore complex-associated about 15-20 nm thick, located at the level of the inner nuclear membrane, which is recognized in thin sections to bridge the interpore distances. With all disintegraiton treatments a somewhat higher susceptibility of the outer nuclear membrane is notable, but a selective removal does not take place. Final stages of disintegration are generally characterized by the absence of identifiable, membrane-like structures. Analysis of detergent-treated nuclei and nuclear membrane fractions shows almost complete absence of lipid components but retention bo significant amount of glycoproteins with a typical endomembrane-type carbohydrate pattern. Various alternative interpretations of these observations are discussed. From the present observations and those of Aaronson and Blobel (1,2), we favor the notion that threadlike intrinsic membrane components are stabilized by their attachment to the pore complexes, and perhaps also to peripheral nuclear structures,and constitute a detergent-resistant, interpore skeleton meshwork.     

Prostaglandin-F-levels in human plasma during late pregnancy and labour (author's transl)

The concentrations of prostaglandin F-equivalents were measured in peripheral plasma during labour at a cervical dilatation of 5 cm and at complete dilatation. After purification, extraction and chromatography the PGF-equivalents were measured radioimmunologically. The intraassay variation was 1.5%, the interassay variation 3.5%. The specificity for PGF was 96-98%. Logit/log transformation of the standardcurve yielded a sensitivity of the assay of 120 pg. At cervical dilatation of 5 cm PGF-equivalents varied between 1300 and 3200 pg/ml plasma. At complete dilatation values changed between 1200 and 5400 pg/ml. These fluctuations correlate timedepending to the uterine contractions recorded and may be interpreted as a result of uterine PGF-release.     

Outcome of moderate carotid artery stenosis in patients who are asymptomatic

PURPOSE: The incidence rate of disease progression and stroke after the diagnosis of a moderate (50% to 79%) carotid stenosis was determined by means of color-flow duplex scanning. METHODS: During a 4-year period, 344 male veterans with moderate internal carotid artery stenoses, on one or both sides, were examined at regular intervals for a mean period of 25 months. Carotid color-flow scans were obtained semiannually. Clinical follow-up was performed to determine the incidence rate of amaurosis fugax, transient ischemic attacks, nonhemispheric symptoms, and strokes. RESULTS: New neurologic symptoms developed in 75 patients (21.8%). Fifty-one (14.8%) had ipsilateral symptoms during follow-up: 18 amaurosis fugax (5.2%), 14 transient ischemic attacks (4%), 5 nonhemispheric symptoms (1.4%), and 14 strokes (4%). Twenty-four patients (6.9%) had contralateral symptoms: 20 strokes (5.8%) and 4 transient ischemic attacks (1.2%). Life-table analysis showed that the annual rate of ipsilateral neurologic events was 8.1%, and the annual rate of stroke was 2.1%. Seventy-five patients (22%) died in the follow-up period. Disease progression to 80% to 99% stenosis or occlusion occurred in 71 of 458 vessels (15.5%). The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs 190 cm/s; P <.0001) and end diastolic velocity (74 vs 52 cm/s; P < 0.0001). Black patients and patients with ischemic heart disease were at a higher risk for disease progression. We could not identify any atherosclerotic risk factors that reliably predicted patients in whom future ipsilateral neurologic symptoms were more likely to develop. However, there was an increased risk of stroke associated with progression of disease. CONCLUSION: Patients who are asymptomatic and who have moderate carotid stenoses are at significant risk for neurologic symptoms and death, but have a relatively low incidence rate of ipsilateral events. The initial flow characteristics in the stenotic vessel are predictive of future disease progression, but they are not helpful in identifying patients in whom symptoms will develop.     

Aureobasidium pneumonia in a post liver transplant recipient: a case report

This is the first report of Aureobasidium (A.) pullulans as an opportunistic pulmonary infection in a liver transplant recipient. A 46-year-old caucasian man had an orthotopic liver transplant in 1988. His liver disease was primary sclerosing cholangitis. He required 2 subsequent liver re-transplants for primary graft non-function and acute rejection. The patient had been living in the California desert for two months prior to admission and presented with ventilator-dependent acute respiratory failure and hemodialysis-dependent acute renal failure. Imaging studies revealed severe bilateral infiltrates. His initial bronchoalveolar lavage (BAL) and brushings grew A. pullulans. Pancultures, including sputum and throat cultures, were negative for bacterial or other fungal organisms. The patient responded to pulmonary support and aggressive systemic antifungal agents while being maintained on cyclosporine and prednisone for immunosuppression. He was discharged to a skilled nursing facility 37 days after hospitalisation. Delay in discharge was primarily due to severe malnutrition and renal impairment. Opportunistic fungal infections continue to be a major problem in immunosuppressed patients including liver transplant recipients. Here we report a pulmonary infection with Coccidioides (C.) immitis and superinfection with A. pullulans. Opportunistic infections such as A. pullulans can be treated successfully with systemic fluconazole when amphotericin B is not well tolerated.     

Distribution of protein phosphatases type 1 and 2A in RINm5F cells

In the insulin producing cell line RINm5F distribution of serine/threonine specific protein phosphatases type 1 (PP1) and 2A (PP2A) was studied. Using different agents which inhibit or stimulate PP1 and PP2A we found that in membrane and nuclear fractions phosphatase activity was inhibited by okadaic acid (OA), protamine, heparin, and inhibitor-2 in a concentration-dependent manner. C2-ceramide had no effect. In the cytosolic fraction the inhibitory effect of okadaic acid was tenfold higher. Protamine stimulated phosphatase activity at low concentrations and became inhibitory at higher concentrations. Inhibitor-2 and heparin caused a decrease in phosphatase activity whereas C2-ceramide led to a slight activation. The data suggest that in membrane and nuclear fractions of RINmSF cells predominantly PP1 is present, whereas in the cytosol PP1 as well as PP2A can be detected.     

Cholinergic responsiveness of neurons in the ventroposterior thalamus of the anesthetized rat

Acetylcholine has been implicated as an important neurotransmitter in the mechanisms of thalamic activation. Cholinergic mechanisms are thought to directly underlie the high level of excitability observed in thalamic relay neurons during waking and rapid eye movement sleep. We sought to determine if the cholinergic responsiveness of neurons in the ventroposterior nuclei of the thalamus in rat is consistent with this view. Neurons in the chloral hydrate-anesthetized rat were studied with extracellular recording and microiontophoretic application of cholinergic agents. In most cases (63% of 63 cells), the ejection of the agonist, carbachol, had no observable effect on spontaneous activity. Facilitation (25%), inhibition (8%) and inhibition followed by facilitation (3%) were also observed. Carbachol ejections that by themselves were ineffective in altering spontaneous activity proved capable, in 93% of 28 cells, of antagonizing the uniformly facilitatory responses produced by glutamate ejection. The putative M1-selective, cholinergic agonist, McN-A-343, was also ineffective alone in altering spontaneous activity in the majority of cases (74% of 27 cells) and produced only inhibitory responses in the remaining seven neurons studied. Interacting applications of McN-A-343 and glutamate resulted, in all cases, in antagonism of glutamate facilitation (N = 12). The various responses to applied cholinergic agonists were all capable of being antagonized by muscarinic receptor-blocking agents. Both the high proportion of inhibitory responses and the antagonism of glutamate facilitatory responses suggest that ventroposterior neurons in the rat differ from other thalamocortical relay neurons in the rat and cat with regard to cholinergic responsiveness. Additionally, the lack of predominantly facilitatory responding renders it unlikely that cholinergic mechanisms directly underlie increases in excitability of ventroposterior neurons observed during waking and rapid eye movement sleep.