Differences among HIV-1 variants in their ability to elicit secretion of TNF-alpha.

HIV-1 infection of human PBMC has been shown to elicit secretion of several different cytokines. TNF-alpha secretion induced by this virus has been of particular interest because it has been associated with the development of HIV-1 dementia and because TNF-alpha increases viral replication by enhancing NF-kappaB interaction with the viral promoter, the HIV-1 long terminal repeat. Thus, an autocrine pathway is potentially created in which HIV-1 stimulates its own replication. Conflicting reports exist, however, on the ability of HIV-1 to induce TNF-alpha secretion in vitro or in vivo. Using experimental protocols that controlled for potential bacterial endotoxin-induced TNF-alpha secretion, the current study demonstrates significant differences in TNF-alpha-eliciting properties among primary and laboratory obtained HIV-1. The relative TNF-alpha-inducing ability of different variants is conserved when tested using PBMC from different individuals. Elicitation of TNF-alpha secretion was not blocked by exposure of cells to zidovudine, indicating that viral integration was not required to induce secretion. Rather, the interaction between the virus and cell surface is critical for TNF-alpha induction, as Abs against CD4 or CCR5 blocked the induction of TNF-alpha synthesis by PBMC when added before virus exposure. Furthermore, the ability to induce TNF-alpha secretion mapped to a region of the HIV-1 env gene that includes the third hypervariable domain. Differences in the ability of different HIV-1 variants to elicit TNF-alpha may account for individual differences in HIV-1 disease course.

Open or arthroscopic lateral release. Indications, techniques, and rehabilitation.

Careful patient selection, accurate surgical technique, and careful postoperative rehabilitation are all equally important to success in lateral release surgery. Whether the surgery is performed by open or arthroscopic technique, one must release all layers of the retinaculum, spare the vastus lateralis, extend the release far enough distally, check intraoperative patellar mobility, and obtain absolute hemostasis. Postoperative rehabilitation must stress pain control, early quadriceps contraction, patellar mobility, and knee motion. With attention to these details, successful lateral release surgery is likely in most patients with pathologic lateral patellar tilt and minimal patellofemoral arthrosis.

The lethality of penetrating cardiac wounds.

The objective was to review our experience in the presentation and management of patients with penetrating cardiac injuries, using physiologic and anatomic indices. The setting was a 400-bed Level I urban trauma center. A 6-year retrospective case study was undertaken. The revised trauma score, physiologic index (PI), penetrating cardiac trauma index, penetrating thoracic trauma index, penetrating trauma index, and cardiac injury organ score were determined. Fifty patients responded to emergency room resuscitation and reached the operating room. Overall survival was 66 per cent. The admission PI correlated well with outcome. Patients presenting in shock (PI, 10; revised trauma score, 7-10) appeared to have higher survival rates when compared to those patients with a normotensive presentation. Twenty-three per cent of patients admitted with a PI < or = 10 died despite reaching the operating room within a mean of 45 minutes. Although the majority of patients who reach the operating room survive, a significant number of (initially normotensive) patients die soon after cardiorrhaphy.

New monoclonal antibodies identify the glycoprotein carrying the CA 125 epitope.

CA 125 is an antigenic determinant located on the surface of ovarian carcinoma cells and elevated in the serum of greater than 90% of patients with carcinoma. The antigen, derived from the ovarian epithelium, has been described as a mucinlike glycoprotein greater than 200 kd. To date little is known of the metabolic regulation or expression of this antigen in either normal or neoplastic tissues. New monoclonal antibodies that we describe here recognize both unique and similar epitopes to OC 125. These reagents may allow for a more complete definition of the structure and expression of the CA 125 complex. These antibodies recognize high-molecular weight (greater than 200 kd) subspecies and a lower-molecular-weight (68 kd) subspecies of the antigen and identify it in the cytoplasm and the extracellular matrix of CA 125-producing cells.

Generating radially polarized beams interferometrically.

Two interferometric techniques for converting a linearly polarized laser beam into a radially polarized beam with uniform azimuthal intensity are described. The techniques are based on the linear combination of orthogonally polarized beams, which have tailored intensity and phase profiles. Linearly polarized beams with intensity profiles tailored using a modified laser or an apodization filter are combined in separate experiments to produce radially polarized light. A beam with an extinction ratio of -21.7 dB and azimuthal intensity variations of less than +/-12% is produced using the modified laser output. The second technique uses circularly polarized light and a unique spiral phase delay plate to produce the required phase profile. When focused, a radially polarized beam has a net longitudinal field useful for particle acceleration and, perhaps, other unique applications.

Effects of prenatal methadone on rat brain catecholamines.

Methadone, injected subcutaneously into Wistar rats during the last trimester of gestation, significantly retarded offspring body and brain growth and the ontogeny of brain catecholamines. On postnatal days 1 and 20, the endogenous content and high affinity uptake of norepinephrine and dopamine were significantly lower in the forebrains of methadone-treated pups than in those of saline or pair-fed control offspring. On day 40, regional norepinephrine levels and uptake were similar in the brains of all three groups. However, the striata of methadone pups remained significantly lower in dopamine content and uptake than did those of saline pups at this age. Hindbrain norepinephrine and dopamine were not altered at any time point. These data indicate that prenatal exposure to methadone more severely retarded body and brain growth than did prenatal undernutrition alone. Furthermore, biochemical indices of the maturation of central catecholamine pathways suggest that prenatal methadone may retard catecholaminergic axonal growth from the hindbrain to the forebrain in rats.

The effects of acute and chronic morphine treatment on the process of facial nerve regeneration.

Prominent cellular responses to axonal interruption include enhanced synthesis of RNA and protein in the neuronal perikaryon, and proliferation of reactive Schwann cells. Since morphine has been shown to significantly depress cellular metabolism, we examined its effect on these and other reparative responses underlying nerve fiber regeneration. Rat facial nerve trunks from saline, acute morphine, and continuous morphine-treated animals were examined by light and electron microscopy at 3, 7 and 14 days after crush injury. The number of axonal sprouts/unit area and the diameters of regenerating axons were quantified at each survival interval. Both saline-treated and acute morphine-treated facial nerves demonstrated myelin degradation and Schwann cell hypertrophy (at 3 days post-axotomy), sprout outgrowth (at 7 days) and axon maturation and myelination (at 14 days). In the chronic morphine-treated animals, a retardation of the regenerative process was evident. Axon sprout outgrowth and axonal diameters were reduced at 3 and 7 days post-axotomy. In treated 14-day animals, axon diameters were normal; however, significantly fewer axon profiles/unit area were observed. After chronic morphine exposure, Schwann cell hypertrophy and proliferation, as well as myelin debris removal, were inhibited at all survival periods.

Structural alterations in normal and axotomized facial nucleus neurons after treatment with morphine.

Chronic morphine administration induced ultrastructural alterations in neurons of the facial nucleus and increased the incidence of cell death after axotomy. These findings may correlate with the significant depression of neuronal metabolism known to occur after opiate treatment.

The effects of acute morphine treatment on the incorporation of [3H]L-lysine by normal and regenerating facial nucleus neurons.

Although opiates significantly alter RNA and protein synthesis in a variety of neuronal cell types, their effect on the biosynthetic activity of regenerating neurons has not been investigated. In the present study, the effect of morphine on the incorporation of [3H]L-lysine into proteins of facial nucleus neurons was examined by light microscopic radioautography. Silver grains present within various compartments of normal and regenerating (3-, 7-, 14- and 21 days post-axotomy) neurons from saline-treated Wistar rats were compared with the amount present in similar cells from animals receiving 40 mg/kg morphine sulfate i.v. At 14- and 21-days post-axotomy, regenerating neurons were larger and the grain count in the emulsion over these cells was greater than that observed in normal (unoperated) neurons. In normal facial neurons, the accumulation of lysine into the nucleus and nucleolus was significantly lower 60 min after morphine administration. However, morphine's inhibition of lysine incorporation was even more pronounced in regenerating neurons. In these cells, nuclear lysine uptake was depressed at 3 and 7 days, while maximum inhibition of cytoplasmic incorporation occurred at 14-days post-axotomy. Morphine administration decreased nucleolar lysine incorporation at all survival intervals.

Prenatal exposure to methadone HCL in relationship to body and brain growth in the rat.

Offspring from methadone-treated Wistar rats (last trimester of pregnancy), as compared to ad lib and pair fed controls, showed a reduction of body growth which continued throughout the 28-day period during which animals were observed after birth. Brain growth, as indicated by weight, cortical thickness and number of cells in the neocortex also showed a reduction in growth, which was apparent only during the first 14 days, after which there were no differences between the groups. However, in the hippocampus, neuronal density changes/unit area continued throughout the 28-day period in the methadone exposed group and to a lesser extent in the PF group suggesting that this area of brain did not return to normal dimensions or degree of maturation by the end of the third week. Since it has been suggested that any deficit in growth associated with prenatalmethadone-exposure might be due to a reduction in food intake, a group pair-fed to the amount of food consumed by the methadone group was included in the study. Generally, the data from the PF group was intermediate between that obtained from the ad lib fed controls and the methadone-exposed animals. Thus, while some of the growth reduction observed in the methadone-exposed pups could have been due to the impaired nutritional status of their mothers during the last third of pregnancy, a part of the reduced growth must be attributed to the drug treatment, since the reduced growth exceeded that observed in the pair-fed group.

Methadone detection in rat myenteric plexus: comparison with findings in the central nervous system by the immunofluorescence method.

Nonpregnant and pregnant rats were given methadone for varying time periods. Myenteric plexus was then examined for methadone by immunofluorescence and the results compared to similar studies of the central nervous system. Nonpregnant animals showed positive ganglion cells 2 weeks before methadone was detected in the brain. Additionally, maternal ganglion cells were more frequently positive than those of their offspring. These findings indicate fundamental differences in the response of peripheral and central neurons to methadone. Thus, studying the effects of opiates on isolated strips of bowel may be of little value in furthering understanding of the action of narcotics upon the brain.

Strain differences in the response to morphine on incorporation of 3H-lysine into rat brain protein.

The effect of morphine on the specific activity (SA) of lysine in the plasma free amino acid (FAA) fraction and in the cerebral cortical FAA and protein fractions, as well as on the specific accumulation and incorporation, was determined in male Sprague-Dawley and Wistar rats at various time intervals after intravenous injection of drug and amino acid into unanesthetized animals. The lysine SA was higher in Sprague-Dawley than in Wistar rats in the plasma and brain FAA fraction and in the protein fraction. In the SD strain, morphine decreased the SA of plasma FAA significantly, but had only slight effects in the Wistar strain. In the cortical gray matter, morphine elevated the SA of lysine significantly in both strains, although the rate of decrease of SA with increasing time after injection was different in the two strains. SA of the lysine in cerebral cortical protein increased in both strains with time, but did so more rapidly in the Sprague-Dawley strain. When the data for the free amino acids were expressed in terms of specific accumulation, the observed rates were higher in the Sprague-Dawley animals and reached a point of maximal concentration, which was not observed in animals of the Wistar strain. Morphine elevated the levels of specific accumulation of lysine into the cortical free amino acid pool in both strains of rat. However, specific incorporation of lysine into the cerebral gray cortical protein in control animlas was essentially similar in both strains. Despite the similarity in specific incorporation of lysine into brain protein in both strains of control rat, morphine treatment caused a much more marked inhibition of incorporation of lysine in the Wistar rats. Thus, it is concluded that Sprague-Dawley and Wistar rats are not equivalent in relation to the accumulation of an amino acid in the brain FAA pool from the plasma and that the effect of morphine on specific incorporation of lysine into brain protein is greater in Wistar rats.

Localization of phenobarbital in mouse central system by immunofluorescence.

Utilizing antibarbiturate serum in an indirect immunofluorescence system, phenobarbital has been detected in the central nervous system of mice given an overdose of drugs. Localizaiton was primarily within neurons of the limbic system, caudate nucleus, cerebellum, cervical spinal cord and trigeminal ganglion. The technic may be of value in acquiring additional information about the barbiturates as well as being of value to the forensic pathologist.

A morphological comparison of the regional distribution of methadone in human and rat brain as demonstrated by immunofluorescence.

The brains of ten narcotic addicts who had died from an overdose of methadone, and the brains of ten rats, given methadone for one month, were examined by the immunofluorescent technic. Positive neuronal fluorescence was seen primarily in the limbic systems of both species as well as in closely associated areas. In the human, Purkinje cell fluorescence was seen in the cerebellum, whereas only stellate cell staining was observed in rat cerebellum. Neurons of the hippocampal denate gyrus often fluoresced in man while only pyramidal cell staining was seen in this region of rat brain. The method should prove to be of value in the detection and tracing of narcotic drugs and may be helpful in investigations of drug tolerance and dependence.