Hepatitis B virus (HBV) variants containing mutations within the X and the precore regions of the viral genome were demonstrated by polymerase chain reaction (PCR) amplification and DNA sequencing in renal dialysis patients with different serological patterns of HBV infection. Among carriers, X region deletion mutants predominated in patients who lost hepatitis B e antigen (HBeAg), or developed anti-HBe, but not in persistently HBeAg-positive patients. The precore region remained wild type in all carriers whether or not they seroconverted from HBeAg to anti-HBe. The frequency of precore and X region mutants was greatest among non-carrier patients with viral antibodies as the only indication of infection and among patients with non-A, non-B hepatitis (NANBH), suggesting an inverse relationship between the presence of wild type HBV markers and the presence of HBV mutants. Furthermore, the detection of one but not the other mutation in many serum samples suggests that these mutations are independently selected for during infection. Finally, the absence of HBV DNA in 21 'uninfected' dialysis patients with normal transaminases and no viral serology, suggests that replication of these mutants is associated with hepatitis. These results have important implications for HBV screening and treatment, as well as for the pathogenesis of chronic infection.

Biomarkers↗

PubMed1995

Parent-to-child transmission is relatively common in the spread of the human polyomavirus JC virus.

JC polyomavirus (JCV), the causative agent of progressive multifocal leukoencephalopathy, is ubiquitous in the human population, infecting children asymptomatically and then persisting in renal tissue. In most adults, renal JCV replicates and the progeny are excreted in urine. We used this urinary JCV to elucidate the routes of JCV transmission. A 610-bp JCV DNA region (IG region) encompassing the 3'-terminal sequences of both T-antigen and VP1 (major capsid protein) genes was amplified by means of PCR from urine specimens collected from all members of seven families. JCV strains were then unequivocally identified by the nucleotide sequences of the amplified IG regions. We could identify 18 distinctive JCV strains from 27 individuals. Different JCV strains were detected from all unrelated persons. However, the same viral strain was detected from one (four families), two (one family), or three offspring (one family) as well as from the fathers (three families) or from the mothers (three families). In total, the JCV strains detected in half of the JCV-positive children were identified in their parents. Since most humans are infected during childhood, these findings indicated that JCV is transmitted frequently from parents to children. We roughly estimated that 50% of JCV transmission occurs by this route and that the other 50% occurs outside the family.

Adult↗

PubMed1995

Parathyroid hormone (PTH)/PTH-related peptide receptor density modulates activation of phospholipase C and phosphate transport by PTH in LLC-PK1 cells.

We showed previously that a single species of cloned PTH/PTH-related peptide (PTHrP) receptors, when stably expressed in LLC-PK1 kidney cells, couples to multiple second messenger signals and biological responses. To address the linkages of individual messenger signals to specific biological responses in these cells, we examined the relations among PTH/PTHrP receptor expression, PTH-activated phospholipase C (PLC) and adenylyl cyclase, and PTH-regulated phosphate transport in LLC-PK1 cells that stably express cloned rat PTH/PTHrP receptors. Among 18 such subclones, PTH stimulation of intracellular cAMP accumulation was nearly equivalent, despite differences in receptor density ranging from 20,000-400,000 sites/cell. In contrast, activation of PLC by PTH was directly and continuously dependent upon receptor density. PTH-stimulated phosphate uptake also was strongly dependent upon receptor expression, correlated well with PLC activity, was mimicked by active phorbol esters but not by cAMP analogs or forskolin, and was strikingly inhibited by the protein kinase C inhibitor, staurosporine. The peptide analog [Arg2]human PTH-(1-34), which significantly stimulated cAMP accumulation but failed to activate PLC, also did not increase phosphate uptake. We conclude that in LLC-PK1 cells, PTH-modulated PLC activation, unlike adenylyl cyclase activation, is strongly dependent upon PTH/PTHrP receptor density. This feature is reflected in the analogous relation between receptor density and PTH regulation of phosphate uptake, which appears to be mediated via a PKC-dependent pathway in these transfected cells. The results suggest that regulation of PTH/PTHrP receptor expression on target cells may provide a mechanism for altering the character as well as the magnitude of the signaling response to the hormone.

Adenylyl Cyclases↗

PubMed1995

Intravenous perflubron emulsion administration improves the recovery of auditory evoked potentials after temporary brain stem ischemia in dogs.

Oxygent, a second-generation perfluorocarbon (Perflubron) emulsion (Alliance Pharmaceutical Corporation, San Diego, CA) with superior oxygen delivery characteristics and greater stability than previous perfluorocarbon emulsions, was evaluated as a cerebroprotective agent in a dog model of partial brain stem ischemia. Six dogs were exposed to 20 minutes of isolated brain stem ischemia after receiving an intravenous bolus of Oxygent at a dose of 1.5 ml/kg. Brain stem auditory evoked potentials (BAEP) and regional cerebral blood flow were measured before and during the ischemia and for 5 hours after reperfusion. Changes in BAEP in this group were compared with those in four control dogs that experienced an identical ischemic period but that did not receive Oxygent. During the ischemic period, both control and Oxygent-treated animals experienced a dramatic decline in BAEP to under 10% of the baseline value. After reperfusion, the BAEP increased in both groups to between 50 and 70% of the baseline. In the Oxygent-treated group, the BAEP continued to recover to a final sustained level of over 80% of baseline. In contrast, the control animals suffered a drop in BAEP to 23% of baseline after the brief postischemic peak. The continued improvement in the BAEP in the Oxygent-treated group compared with the control groups suggests that Oxygent may be of some value as a protective agent to the brain stem during ischemia. This effect may be the result of improved oxygen delivery to the brain stem or may be related to other effects of Oxygent, such as reduction of reperfusion injury. Results suggest that Oxygent may be useful as a cerebroprotectant during cerebrovascular surgeries that require temporarily reducing blood flow to the brain stem.

Animals↗

PubMed1995

A canine model of acute hindbrain ischemia and reperfusion.

Animal models of brain stem ischemia are needed for pathophysiological study and evaluation of treatment; few such models are available currently. A new canine model of hindbrain ischemia and reperfusion is introduced in this article. Through an anterior cervical approach, the basilar artery was surgically exposed in 18 dogs. The posterior communicating and superior cerebellar arteries were embolized with cyanoacrylate glue to isolate the posterior circulation from the anterior circulation. Reversible hindbrain ischemia was induced in 14 dogs by the temporary clipping of the vertebral and ventral spinal arteries for various periods (10-30 min), then the clips were removed and reperfusion was achieved for 5 hours. In all 14 dogs, the hindbrain ischemia was confirmed by the decreased perfusion pressure in the basilar artery (< 10 mm Hg), the diminished regional cerebral blood flow as measured with a laser Doppler flowmeter at the medulla oblongata (< 10 ml/100 g/min), the flattened brain stem auditory evoked potentials, and the increased leakage of Evans blue dye from tissue. These parameters did not change in the four control dogs. The changes in brain stem auditory evoked potentials were closely related to the length of ischemic interval; after 10 minutes of ischemia, reperfusion fully reversed the changes in brain stem auditory evoked potentials, but 20-minute and 30-minute ischemic intervals partially or totally depleted the brain stem auditory evoked potentials. Delayed postischemic hypoperfusion occurred in all five dogs that underwent the 30-minute ischemic interval. The early physiological changes in this model allowed us to estimate the severity of brain stem ischemia and the resulting damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1995

The protective effects of thiopental on brain stem ischemia.

Thiopental, a barbiturate anesthetic, which at high doses suppresses cortical electroencephalogram activity, was evaluated as a neuroprotective agent in a dog model of reversible, hindbrain ischemia. Fourteen dogs were exposed to 20 minutes of isolated brain stem ischemia after pretreatment with 35 mg per kg of thiopental or placebo. Brain stem auditory evoked potentials (BAEPs) and regional cerebral blood flow were measured before and during the ischemia and for 5 hours after reperfusion. During the ischemic period, both control and thiopental-treated animals experienced dramatic declines in the BAEPs to less than 10% of baseline. On reperfusion for 30 minutes, the BAEPs increased in both groups to near 40% of baseline. In the thiopental-treated animals, the BAEPs continued to recover variably to a mean of 70% of baseline by 5 hours of reperfusion. In contrast, untreated animals showed a decline in BAEPs after 30 minutes of reperfusion. The improved recovery of BAEPs in the thiopental-treated animals suggests that thiopental may be of some value as a cerebroprotective agent, although the mechanism remains unclear. The variability in recovery in this group implies that other factors play a significant role in mediating functional recovery from ischemic brain stem damage.

Anesthetics, Intravenous↗

PubMed1995

Elimination of self-peptide major histocompatibility complex class I reactivity in NOD and beta 2-microglobulin-negative mice.

Nonobese diabetic (NOD) mice and beta 2-microglobulin-gene-ablated mice (beta 2M -/-) show impaired presentation of major histocompatibility complex (MHC) class I and self-peptides, structures now recognized as critical for T-cell education to endogenous peptides. The naturally occurring NOD class I presentation abnormality appears to be attributable to, in part, a quantitative defect in the production of Tap-1 mRNA; Tap-1 with Tap-2 normally functions as a transporter for stable self-peptide and class I assembly. This study attempts to reverse NOD and beta 2-M -/- mouse autoreactivity by introduced or reestablished syngeneic class I presentation. Introduction of MHC class I and self-peptides on syngeneic MHC class I-matched cells specifically prevented diabetes in NOD mice and eliminated in vitro class I-directed T-cell autoreactivity in NOD and beta 2M -/- mice. Reestablishment of endogenous class I and self-peptide presentation in NOD mice was achieved with two well-described cures for the NOD mouse, complete Freund's adjuvant and mouse hepatitis virus. Both treatments induced Tap-1 mRNA, reestablished class I presentation of endogenous antigens, and eliminated in vitro and in vivo T-cell autoreactivity of self-peptides in the class I groove. These results substantiate a therapeutic role of self-peptide complexed with class I for T-cell education and suggest that some well-described NOD treatments may work, in part, through reestablishment of tolerance through class I and self-peptide.

Aging↗

PubMed1995

Limited protective effects of etomidate during brainstem ischemia in dogs.

To evaluate etomidate as a neuroprotective agent in the brain stem, 33 dogs were divided into seven groups and were exposed to isolated, reversible brainstem ischemia in the presence or absence of etomidate using a newly developed canine model of brainstem ischemia. Brainstem auditory evoked potentials (BAEP) and regional cerebral blood flow were measured during ischemia and for 5 hours after reperfusion. This model provides a potential physiological environment in which to test the efficacy of putative brainstem ischemic protective strategies. During ischemia, BAEP were abolished in all animals. Without etomidate 10 minutes of ischemia was of short enough duration to allow complete recovery of BAEP. Ischemia of 20 or 30 minutes' duration resulted in minimal recovery. The dose of etomidate administered did not suppress BAEP or brainstem cardiovascular response to ischemia. In animals receiving etomidate and rendered ischemic for 20 minutes, a significant but only temporary recovery in BAEP was seen. Etomidate failed to have a significant effect in animals rendered ischemic for 30 minutes. The minimal effect of etomidate on the current measures of brainstem function is in contrast to etomidate's known suppressive effect on cortical electroencephalogram and predicts that etomidate does little to alter brainstem metabolism. Etomidate's failure to provide for permanent recovery of BAEP suggests that the drug does not give sufficient protection from ischemia to the brainstem neurons in the auditory pathway. If these auditory neurons reflect brainstem function as a whole, etomidate may not be the protective agent of choice during temporary arterial occlusion of posterior circulation.

Animals↗

PubMed1995

The Alabama Medicaid DUR Program.

Explore the source record for details and available documents.

Alabama↗

PubMed1995

Progress in diagnostic and therapeutic techniques of cardiovascular diseases in China 1994.

Explore the source record for details and available documents.

Angioplasty, Balloon, Coronary↗

PubMed1995

Structural requirements of parathyroid hormone/parathyroid hormone-related peptide receptors for phospholipase C activation and regulation of phosphate uptake.

Explore the source record for details and available documents.

Animals↗

PubMed1995

[Effect of electric fields on the proteins in nerve regeneration conditioned fluid].

80 SD rats were randomly divided into four groups of 20 each: local electrostimulation of nerve stump (Group LS); electro-stimulation of myeloneure (Group N); electrostimulation of the denervated muscle (Group M); and controls (Group C). The left lateral sciatic nerve of rats was excised 5mm in length, and the severed nerve was bridged with the silicon tube. The gap between the stumps was about 10mm. At 3rd, 7th, 14th, 21st and 28th day after nerve transection and tube implantation, the fluid in the silicon tube was aspirated. The sample of fluid was spun and 4 microliters aliquots were taken from the supernatant. Then the electrophoresis of the aliquots was made by phase-system and assayed to the amount and variety by Gel Scan system. The results showed that the group LS had a high increase in the protein amount than others in the range of 6.16-10.23 x 10(3)D molecular weight. We believe that it is one of the mechanisms of the electric fields promoting nerve regeneration.

Animals↗

PubMed1995

[Variant gap phenomenon in A-V conduction].

In 361 consecutive patients 4 with variant gap phenomenon (VGP) underwent intracardiac electrophysiological studies. The premature atrial response initially delayed in His-Purkinje system (HPS) which had a long relative refractory period (RRP), and H-V interval was prolonged. However, as atrial responses were more premature, the atrioventricular node (AVN) showed RRP and slowed down the conduction, that made HPS get rid of RRP before the response arriving. Thus the conduction resumed, and H-V interval became normal. It was different from the classic gap phenomenon. We call it variant gap phenomenon.

Adult↗