Studies of Antibody to Herpes Simplex Virus Fcγ-Binding Protein gE in Patients with Rheumatoid Arthritis, Juvenile Rheumatoid Arthritis and Normal Controls

IgG antibody to gE, the Fc gamma-binding herpes simplex 1 (HSV-1) viral glycoprotein, was studied in 49 rheumatoid arthritis (RA) patients and 43 normal controls. Antibody to gD, another important HSV-1 antigen, was assayed in parallel. No difference between RA patients and normal controls was found in levels of anti-gE antibody measured by reactivity of IgG F(ab')2 fragments reacting with gE coated to ELISA plates. No difference in anti-gD antibody was recorded between normals and patients with RA. Levels of IgG anti-IgE antibody did not correlate with quantitative elevations of serum rheumatoid factor (RF) in RA patients. When IgG anti-gE and anti-gD were assayed in 20 patients with juvenile rheumatoid arthritis and 22 children controls, no significant differences were noted. However, when individual RFs from patients with RA were tested for reactivity against a panel of affinity-isolated F(ab')2 antibodies to gE, some evidence for individual autospecificity was obtained. Four of 20 monoclonal IgM RFs produced from RA patients' B cells showed marked elevations of reactivity with some RA patients' F(ab')2 antibodies to gE. All four of the monoclonal RFs showing this specificity were derived from RA synovial tissue B cells. These findings may provide support for the concept that some RFs in patients with RA show individual specificity for internal image determinants of IgG antibodies to viral Fc gamma-binding proteins.     

EFFECT OF NITROGLYCERNE-INDUCED HYPOTENSION ON CANINE SPINAL CORD BLOOD FLOW

Twenty-four mongrel dogs were anaesthetized with pentobarbitoneand morphine sulphate. Neuromuscular blockade was achieved usingpancuronium. Spinal cord blood flow was measured using the radionuclidemicrosphere and hydrogen washout methods before, during, andfollowing nitroglycerine-induced hypotension. Heart rate, meanarterial pressure, cardiac output, pulmonary capillary wedgepressure, and acid-base balance were determined with each measurement.Mean arterial pressure was reduced by 50%. Spinal cord bloodflow, as measured by the microsphere method, increased duringthe period of hypotension, whereas values obtained using thehydrogen washout method were not significantly different fromthose at normotension. No significant change in spinal cordblood flow was detected by either method after the applicationof spinal distraction. Nitroglycerine acts predominantly onvenous capacitance vessels and it is postulated that perfusionpressure, and therefore flow, is maintained despite a reductionin arterial pressure. Presented in part at the Anual Meeting of the American Societyof Anesthesiologists, October 1985, San Francisco, California. ^*Shackleton Department of Anaesthetics, Southampton GeneralHospital, Shirley, Southampton, Hants SO9 4XY. Section of Orthopedic Surgery, Madison, Wisconsin.     

The Effects of Magnetic Resonance Imaging on Implantable Pulse Generators

The effects of magnetic resonance imaging were assessed on four dual chamber and two single chamber pulse generators. The tests were performed with a resistive, water-cooled magnet operating at 0.15 T. The 6.4-MHz radiofrequency (RF) field was operated at a maximum power of 1,000 watts with a period adjusted from 130 to 500 ms. Reed switch closure occurred in all six pulse generators tested when placed near the entrance of the magnetic resonance imaging scanner, and the generators reverted to asynchronous operation unless programmed to the "magnet off" mode. None of the pulse generators exhibited any alterations in programmed parameters or in the ability to be reprogrammed after RF pulsing. When the RF field was turned on, there was no change in the asynchronous paced cycle length in four pulse generators; however, during RF scanning there was rapid cardiac stimulation at the RF pulse period in one single chamber and one dual chamber pulse generator.     

Developmental Neurotoxicity: Evaluation of Testing Procedures with Methylazoxymethanol and Methylmercury

Testing procedures for identification of potential developmentalneurotoxicants were evaluated using two prototypical developmentalneurotoxicants, methylazoxymethanol (MAM) and methylmercury(MeHg). Evaluation of offspring of LongEvans rats incorporatedassessments of developmental toxicity, neurochemistry, histology,and behavior, with most testing being completed near weaning.A number of endpoints in the testing strategy were sensitiveto the effects of prenatal exposure to MAM [30 mg/kg on GestationDay (GD) 15]: (1) MAM caused reduced neonatal body weights butdid not effect viability or postnatal survivorship; (2) measurementof total and regional brain weight and histological analysisshowed that a number of regions, the cortex and hippocampusin particular, were affected by MAM exposure; (3) an assay forglial fibrillary acidic protein (GFAP) showed that the concentrationof this protein was significantly increased in the cortex andhippocampus of treated offspring; (4) a T-maze delayed-alternationprocedure indicated that MAM-treated pups were slower in theacquisition phase of the task relative to control pups; (5)motor activity testing revealed hyperactivity in treated offspringthat persisted into adulthood; and (6) acoustic startle proceduresrevealed reduced startle amplitudes in preweanlings. Few endpointswere significantly affected by prenatal MeHg exposure (1, 2,or 4 mg/kg on GD 6–15). High fetal and neonatal mortalityand lower neonatal body weights were detected at the highestdose of MeHg. Although minimal effects of MeHg may reflect arelative insensitivity of the test species and/or the test methods,the combined results from both chemicals suggest that some proceduresnot currently required in the developmental neurotoxicity guidelinemay be useful in hazard identification, and further evaluationwith other chemicals, species, strains, and/or exposure paradigmsmay be warranted.     

Chronic Marijuana Smoke Exposure in the Rhesus Monkey I. Plasma Cannabinoid and Blood Carboxyhemoglobin Concentrations and Clinical Chemistry Parameters

Chronic Marijuana Smoke Exposure in the Rhesus Monkey I. PlasmaCannabinoid and Blood Carbxyhemoglobin Concentrations and ClinicalChemistry Parameters SLIKKER, W., JR., PAULE, M. G., ALI, S.F., SCALLET, A. C., AND BAILEY, J. R (1991). Fundam. Appl Toxicol17, 321–334. This report is the first in a series abouta large multidisciplinary study designed to determine whetherchronic marijuana (MJ) smoke exposure results in residual behavioraland/or neuropathological alterations in the rhesus monkey. Priorto the initiation of a year of chronic MJ smoke exposure, 64periadolescent male rhesus monkeys were trained for 1 year toperform five operant behavioral tasks and then divided, accordingto their performance in these tasks, into four exposure groups(n=15–16/group): (1) a high dose (HI) group, exposed 7days/week to the smoke of one standard MJ cigarette; (2) a lowd m (LO) group, exposed on weekend days only to the smoke ofa standard MJ cigarate; (3) an extracted MJ cigarette (EX) group,exposed 7 days/week to the smoke of one ethanol-extracted MJcigarette; and (4) a sham group (SH), exposed 7 days/week tosham exposure conditions. Daily exposures for 1 year were accomplishedusing a mask that covered the subjects' nose and mouth. Averagebody weights (initially 3.7?0.5 kg, mean?SD) and rates of weightgain (approximately 0.1 kg/month) were the same for all groupsthroughout the entire experiment. During the first week of expsure,plasma concentrations of -9-tetrahydrocannabinol and 11-nor-9-carboxy-THCin the HI group were 59?7 (mean?SE) and 5.5?1.5 ng/ml, respectively,45 min after MJ smoke administration and did not change significantlyat similar times after exposure throughout the remainder ofthe year. Whole blood carboxyhemoglobin levels increased toapproximately 13% 1 min after expsure to smoke in either theMJ or the EX groups. Comparison of blood chemistry and hematologyvalues before, during, and after exposure indicated no differencesfor most parameters. During exposure, lymphocytes, alkalinephosphatase and -glutamyl transferase were depressed in theHI group compared to in the SH group. During exposure, aspartateaminotransferase was elevatd for both the HI and EX groups,suggesting a general effect of smoke exposure. Because theseeffects were transient and remained within the range of reportednormal values, these data indicate that long-term, experimentalexperimental exposure to MJ smoke is feasible and does not compromisethe general health of the rhesus monkey.     

Cerebrospinal fluid viral load is related to cortical atrophy and not to intracerebral calcifications in children with symptomatic HIV disease

The relationships between viral load in plasma and cerebrospinal fluid (CSF) and computed tomography (CT) brain scan abnormalities were studied in 39 children between 0.5 and 13 years of age with symptomatic HIV-1 disease. Quantitative RNA PCR was used to determine HIV-1 RNA levels and a semiquantitative analog rating technique was used to evaluate non-contrast CT brain scans. CSF HIV-1 RNA copy number correlated significantly with CT brain scan ratings for severity of cortical atrophy (r = 0.36; P < 0.05) but not with ratings of intracerebral calcifications (r = -12; NS). The difference between these two correlations was significant (P < 0.05). Plasma HIV-1 RNA copy number did not correlate significantly with any CT brain scan ratings or with CSF viral load (r = 0.05; NS). Severity of cortical atrophy appeared to reflect the level of viral load in the CSF, supporting the notion that active HIV-1 replication in the CNS is at least in part responsible for such brain abnormalities in children. The lack of correlation of intracerebral calcifications with other CT brain scan abnormalities as well as with CSF viral load suggests that this lesion is relatively independent and may reflect a different neuropathologic process.     

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.      

Advances in computer-assisted single-photon emission computed tomography (SPECT) for epilepsy surgery in children

Epilepsy surgery has emerged as an important option in the treatment of children with epilepsy that is refractory to antiepileptic drug management. The cornerstone of successful surgery is accurate localization of the brain region of seizure onset. Traditional techniques of seizure onset localization, e.g. surface electroencephalography (EEG) recording and magnetic resonance imaging (MRI), allow accurate localization in a significant number of patients. When the focus of seizure onset is not apparent from these non-invasive techniques, other methods of localization, e.g. intracranial EEG recording, may be needed before resection of the focus. Single-photon emission computed tomography (SPECT) is a nuclear medicine blood-flow technique that has been used to identify a region of epileptogenic brain associated with low blood flow in the resting state (interictal SPECT) or increased blood flow at the time of seizure activity (ictal SPECT). This report describes the validation and utility of a computer-assisted method of subtracting the interictal from the ictal SPECT scans and co-registering the difference image on the MRI. This method, called subtraction ictal SPECT co-registered on MRI (SISCOM), is used in guiding the location and the extent of intracranial electrode implantation, or in obviating the need for the implantation in some cases.