Serotypic and genotypic characterization of human serotype 10 rotaviruses from asymptomatic neonates.

Human rotaviruses were isolated from asymptomatic neonates at various hospitals and clinics in the city of Bangalore, India, and were found to be subgroup I specific and possess long RNA patterns (M. Sukumaran, K. Gowda, P. P. Maiya, T. P. Srinivas, M. S. Kumar, S. Aijaz, R. R. Reddy, L. Padilla, H. B. Greenberg, and C. D. Rao, Arch. Virol. 126:239-251, 1992). Three of these strains were adapted to tissue culture and found by serotype analysis and neutralization assays to be of serotype 10, a serotype commonly found in cattle but infrequently found in humans and not previously identified in neonates. By RNA-RNA hybridization, a high level of relatedness to a serotype 10 bovine rotavirus strain and a low-to-medium level of relatedness to a human rotavirus strain were observed. Since this human isolate shares a genogroup with bovine rotavirus, it is likely that it originated by interspecies transmission. A human rotavirus strain isolated from asymptomatic neonates and similar to bovine rotavirus might represent a good vaccine candidate.     

Characterization of high affinity binding between laminin and Alzheimer's disease amyloid precursor proteins.

BACKGROUND: In vivo amyloid formation apparently involves several extracellular matrix components that are usually found associated with basement membranes. These include laminin, heparan sulfate proteoglycan, collagen type IV, and entactin. These components have also been found in neuritic plaques. We have therefore been examining interactions between extracellular matrix components and the Alzheimer's amyloid precursors (AAPs). EXPERIMENTAL DESIGN: Binding interactions of laminin with AAP-695, -751, and -770 were examined using a solid phase enzyme-linked immunosorbent assay technique. RESULTS: Objective, quantitative analyses of the laminin AAP-695, -751, and -770 binding data reveal two binding sites for laminin, with Kd values of 1 x 10(-10) M and 1 x 10(-8) M. Zinc and dithiothreitol profoundly stimulate laminin binding to AAPs. Furthermore, zinc fingers were found in the laminin amino acid sequences. Previous binding studies of AAPs with the basement membrane heparan sulfate proteoglycan revealed similar affinities. A particular order of addition of laminin and heparan sulfate proteoglycan to AAPs can be demonstrated. CONCLUSIONS: These avid interactions with extracellular matrix proteins likely reflect normal functions of the AAPs and may be involved in nucleation events in Alzheimer-type amyloid formation.     

The "hyperacute" extraaxial intracranial hematoma: computed tomographic findings and clinical significance

Thirteen patients with acute subdural and epidural hematomas were found to have fresh, unclotted blood at the time of surgical decompression several hours after injury. Computed tomographic (CT) scans of these patients demonstrated areas of hyperdensity, corresponding to clotted hematoma, admixed with areas of isodensity, corresponding to liquid blood. Active bleeding from identifiable loci was found in 11 patients, 4 of whom had massive hemorrhages. Clotting abnormalities ranging from slightly elevated laboratory test results to a full-blown clinical picture of disseminated intravascular coagulation occurred in 8 patients. We describe the CT pictures of these "hyperacute" lesions, and we postulate that such CT presentations indicate either the presence of ongoing active intracranial bleeding or the onset of a coagulopathy complicating the management of these lesions.     

Systemic and transcardiac platelet activity in acute myocardial infarction in man: resistance to prostacyclin

There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore an understanding of factors that influence platelet performance is important. This study was undertaken (1) to characterize during evolving myocardial infarction platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and (2) to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving myocardial infarction were studied. Twenty-two patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 min. In 15 patients with anterior myocardial infarction, transcardiac platelet function and response to PGI2 were studied. Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, were elevated three- and 10-fold. 6-Keto-prostaglandin F 1 alpha, the stable end product of PGI2, was less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets circulating during evolving myocardial infarction ("ischemic platelets") were hyperaggregable in response to ADP and relatively resistant to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic AMP and the cyclic AMP response to PGI2 were diminished. The platelet hyperreactivity, expressed by plasma beta-TG, platelet aggregation, and PGI2-induced inhibition of aggregation, was most intense early during infarct evolution and decreased with time. The increased platelet performance resulted in "platelet fatigue," indicated by decreased contents of beta-TG of the ischemic platelet and decreased TxA2 production in response to collagen. However, the ischemic platelet produced twice normal TxA2 in response to arachidonic acid (stimulus and substrate), demonstrating a heightened metabolic capacity. TxA2 was produced across the ischemic/infarcting compartment in 10 of 15 patients with anterior myocardial infarction. The antiplatelet effect of PGI2 was greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving myocardial infarction, characterized by a proaggregatory environment, heightened platelet reactivity in both the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequences of the data are that the patient in the acute phase of myocardial infarction may benefit from suppression of platelet function and requires significantly greater doses of PGI2 than normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)     

Precipitation of fibrinogen, fibrinogen degradation products and fibrin monomer by histone H3

Incubation of histone H3 with normal citrated plasma resulted in the formation of insoluble aggregates, as determined by turbidity measurements. The precipitate was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, confirming that fibrinogen was a major component. Purified fibrinogen precipitated rapidly as determined with turbidity experiments and experiments with radioiodinated protein. The amount of fibrinogen precipitation was strongly dependent on H3 concentration. Variation of ionic strength (0.2-0.84) and pH (5.3-7.4), however, had little or no effect on the reaction. Fibrinogen subjected to gelatin-Sepharose chromatography or dialysis against 3.3M urea reacted equivalently with H3. Precipitation of 125I-fibrinogen by H3 was strongly favored by increasing temperature (4 degrees-45 degrees C). Precipitation of fibrinogen by protamine was maximized by decreasing the temperature. In addition, formation of insoluble fibrinogen-protamine aggregates was highly dependent on ionic strength and pH, suggesting that different types of protein-interaction are involved in the two studied precipitation reactions. Of the fibrinogen degradation products, only fragment X precipitated significantly when incubated with H3. Radioiodinated fibrin monomer also precipitated when incubated with H3 in solutions of sufficient ionic strength to prevent spontaneous polymerization. The extent of precipitation was equivalent for fibrin monomer and fibrinogen. Fragment D inhibited the precipitation of fibrinogen by H3 or protamine. These studies indicate that the proteins termed "paracoagulants" are not all equivalent and that the hydrophobic domain of H3 plays a critical role in fibrinogen precipitation.     

Overproduction and purification of the luxR gene product: Transcriptional activator of the Vibrio fischeri luminescence system

Expression of Vibrio fischeri luminescence genes requires an inducer, termed autoinducer, and a positive regulatory element, the luxR gene product. A plasmid containing luxR under control of a tac promoter was engineered to overproduce this gene product. The overproduced luxR gene product was active in vivo, and its apparent monomeric molecular weight was indistinguishable from that of the protein encoded by luxR under control of its own promoter (M(r) 27,000). The new tac-luxR construct directed the synthesis of large quantities of the luxR gene product in induced Escherichia coli cells lacking other lux genes. In the presence of the other lux genes, overexpression of the tac-luxR construct was not detected. The overproduced luxR gene product, which formed cytoplasmic inclusion bodies, was purified and used in subsequent studies. Nonequilibrium pH gradient electrophoresis indicated that the protein was basic, and the amino-terminal 15 amino acids were sequenced. DNA-binding activity was detected by membrane filter binding assays; under the conditions used, the binding was not lux DNA-specific. Binding of tritium-labeled autoinducer to the luxR gene product was not detected, and autoinducer enhancement of the binding of the luxR gene product to DNA could not be detected reproducibly.     

Serial Dexamethasone Suppression Tests and Clinical Outcome in ECT

Serial dexamethasone suppression tests (DST), obtained during a course of electroconvulsive therapy in 43 severely depressed patients, did not exhibit relationships between the initial DST, final DST, or the change in DST with clinical outcome measures at the time of discharge. In 37 patients reviewed six months after discharge, no relationship with the continuation of improvement, rehospitalization, or suicide was found. We are unable to confirm a clinical application for the DST in the management of patients during a course of convulsive therapy.     

Comparison of primary and secondary treatment in squamous oral cancer

A popular rule of thumb has often prevailed in treating oral cancer: Try one modality first; if it fails, try the other--the chance for cure will still be good. To study this dogma, a group of 160 consecutive patients with oral cavity squamous carcinoma were reviewed. A hypothesis was formed: secondary treatment for recurrent cancer, whether surgery after radiation failure or vice versa, would salvage essentially as many patients as primary treatment, say within 15%. Results show a large difference in success rates between first and second treatments when all stages are considered together, a difference well over 15 percentage points. Regarding each stage separately, the largest difference occurs in stage II (28 percentage points); other stages exceed 15 point differences. No significant differences in successful salvage occur between "home" failures and "elsewhere" failures. Local recurrence was a major cause of failure in both groups (55%). We conclude that recurrence of oral squamous cancer after first treatment markedly reduces patients' chance for cure.     

Lupus vulgaris responding to double antituberculous therapy

A patient with a 3 by 4 cm ulcerated lesion on the nose and upper lip in whom previous antibiotics and antifungal treatments for a "mixed infection" were of no avail is presented. Her history revealed that she has had pulmonary and pharyngeal tuberculosis and subsequently scrofuloderma of cervical lymph nodes. She eventually responded well to isoniazid, rifampin, and pyridoxine therapy.     

Universal Mindfulness Training in Schools for Adolescents: a Scoping Review and Conceptual Model of Moderators,Mediators, and Implementation Factors

Prevention Science - There is evidence that universal school-based mindfulness training (SBMT) can have positive effects for young people. However, it is unknown who benefits most from such...