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M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 271 records · Page 15Linked to original sources
PubMed1996

Accumulation of tyrosine hydroxylase messenger RNA molecules in the rat mesencephalon by chronic caffeine treatment.

In the present study we assessed the effect of chronic treatment with caffeine on the levels of the messenger RNA molecule encoding the enzyme tyrosine hydroxylase (TH) by in situ hybridization histochemistry in the ventral tegmental area (VTA) and the substantia nigra compacta (SNc) of the rat brain. Animals that received caffeine for nine consecutive days at doses of 20, 40 and 80 mg/kg of body weight displayed increased TH mRNA levels in the SNc (up to 64% above vehicle-injected controls) and the VTA (33% above controls). Moreover, the increases observed at 80 mg/kg of caffeine were prevented by concurrent administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (0.25 mg/kg). These results demonstrate that chronic exposure to caffeine, an adenosine A2 receptor antagonist, alters the levels of expression of the mRNA encoding the rate limiting enzyme in catecholamine biosynthesis.

Animals↗
PubMed1996

The role of radioimmunoscintigraphy and computed tomography scan prior to reassessment laparotomy of patients with ovarian carcinoma. A preliminary report.

BACKGROUND: Accurate evaluation of patients with ovarian carcinoma who have completed primary therapy often requires surgical exploration. Radioimmunoscintigraphy (RIS) represents an evolving technique that may allow noninvasive detection and localization of persistent or recurrent disease in these patients. METHODS: Our prospective, blinded study enrolled patients with normal CA 125 levels and no clinical evidence of disease after primary cytoreductive surgery and cytotoxic chemotherapy for ovarian carcinoma. Each patient underwent RIS using Indium-satumomab pendetide (labeled antibody B72.3 to the tumor-associated antigen TAG-72) and abdominal/pelvic computed tomography (CT) prior to reassessment laparotomy. RESULTS: Twenty patients were enrolled from January 1994 to January 1995. Two patients with negative RIS scans refused reassessment laparotomy and were without evidence of disease > 15 months from the study. Twelve of the remaining 18 patients (66.7%) had histologically proven disease at reassessment laparotomy. RIS images indicated the presence of disease in all 12 patients, whereas CT scans detected disease in only 2 patients. In three of five patients, biopsy-proven microscopic disease (no gross disease at the time of laparotomy) was found only in specimens obtained by RIS-directed biopsies. RIS was superior to CT in sensitivity (100% vs. 16.7%), accuracy (72% vs. 33%), and negative predictive value (100% vs. 28.6%) (P < 0.005). CONCLUSIONS: Routine use of CT is of limited value in the assessment of ovarian carcinoma patients with negative physical examinations and normal CA 125 levels. With its high level of sensitivity and negative predictive value, RIS may play a role in the detection of persistent disease in this population and aid in the classification of patients into three distinct groups: those with gross residual disease, small volume or microscopic disease, and no disease. Separation of this heterogenous group without surgery may help guide subsequent consolidation therapy. However, attaining a high level accuracy with RIS, depends on optimizing the method of image acquisition, the timing of scans, and the reconstruction of data.

Animals↗
PubMed1996

Hyperstimulation of leukocytes by plasma from cardiopulmonary bypass patients is diminished by alpha-MSH pretreatment.

Cardiopulmonary bypass (CPB) results in a diffuse inflammatory response characterized in part by hyperstimulation of leukocytes. We have previously shown that this hyperstimulation appears to be due, in part, to an increase in the release of biological response modifiers (BRMs) such as cytokines. In the present study, we evaluated the ability of a naturally occurring immunocyte inhibitory substance, alpha-melanocyte-stimulating hormone (alpha-MSH), to prevent the hyperstimulation caused by CPB. Monocytes and granulocytes were pretreated with alpha-MSH (10(-6) M) before exposing the cells to plasma obtained from patients who had undergone CPB, as CPB plasma would stimulate native monocytes and granulocytes in a manner similar to that observed in CPB patients. Pretreatment of these cells with alpha-MSH significantly diminished the hyperstimulation induced by CPB plasma in a concentration-dependent manner. In contrast, when the cells were first or simultaneously exposed to CPB plasma and then to alpha-MSH, alpha-MSH had no effect. Furthermore, use of the specific neutral endopeptidase inhibitor, phosphoramidon, significantly increased the efficacy of alpha-MSH in inhibiting CPB-induced immunocyte activation. The data demonstrate that pretreatment of monocyte/macrophages and granulocytes with alpha-MSH effectively inhibits the immune hyperstimulation induced by CPB-plasma exposure. In addition, the data strongly suggest that preexposure to other naturally occurring immune inhibitory substances may diminish the hyperstimulation associated with CPB. The study also further confirms that this hyperstimulation may, in part, be due to BRMs released from immunocytes.

Cardiopulmonary Bypass↗
PubMed1996

Action of beta-phenylethylamine and related amines on nigrostriatal dopamine neurotransmission.

The present paper describes the effect of beta-phenylethylamine and its metabolites phenylethanolamine, tyramine, acetyl-phenylethylamine and phenylacetaldehyde on the dopaminergic nigrostriatal system. The rotational behavioural response to the i.v. injection of these drugs was quantified in animals with a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine system. Only beta-phenylethylamine and acetyl-phenylethylamine induced rotations ipsilateral to the side of the brain lesion. None of the compounds under study stimulated contralateral rotations. Acetyl-phenylethylamine was 90% less active than beta-phenylethylamine. After beta-phenylethylamine injection all animals (16/16) showed ipsilateral rotations. The dose-response curve showed that at doses as low as 1.75 mg/kg ipsilateral turns increase, with a dose-related rotational response between 1.75 mg/kg and 11.66 mg/kg, no differences being found at doses between 11.66 and 29.16 mg/kg. Rotations began a few seconds after beta-phenylethylamine injection. The highest response was found 30-60 s after the injection. The duration of the response was dose-related (4 min for the 3.5 mg/kg doses). The inhibition of dopamine-beta-hydroxylase activity with [1-3,5-difluorobenzyl)imidazole-2-thiol (SKF102698) did not modify the rotational response to beta-phenylethylamine. The inhibition of type B monoamine oxidase activity with l-deprenyl induced a slight increase in the ipsilateral rotational response to beta-phenylethylamine. The inhibition of tyrosine hydroxylase activity with alpha-methyl-p-tyrosine decreased the rotational response to beta-phenylethylamine. The dopamine receptor antagonist, haloperidol, completely blocked the ipsilateral rotational response to beta-phenylethylamine. The blocking of dopamine uptake into storage vesicles with reserpine increased the rotational action of beta-phenylethylamine. Taken together, the data suggest that, at low doses, beta-phenylethylamine stimulates the release of dopamine from the cytoplasmic pool and behaves as a dopamine receptor agonist with a very rapid and brief action.

Amines↗
PubMed1996

Monoclonal autoantibody SCH94.03, which promotes central nervous system remyelination, recognizes an antigen on the surface of oligodendrocytes.

A monoclonal antibody SCH94.03, made in syngeneic mice by injection of spinal cord homogenate, promotes central nervous system remyelination when injected into SJL/J mice chronically infected with Theiler's virus. To elucidate the mechanism of antibody-mediated remyelination, SCH94.03 was investigated by immunocytochemistry, flow cytometry, immunoelectron microscopy, Western blotting, and immuno-thin layer chromatography. All cell types investigated in vitro showed strong cytoplasmic staining with a pattern resembling a cytoskeletal protein. In contrast, among the primary cultured cells studied, only oligodendrocytes showed strong surface reactivity. Other cell types, including astrocytes, microglia, Schwann cells, myoblasts, and T and B lymphocytes, were negative. Mouse and rat oligodendrocytes which showed strong surface reactivity exhibited a well-differentiated morphology, and approximately 50% expressed myelin basic protein. Since oligodendrocyte progenitors were negative for surface staining, the expression of the antigens recognized by this monoclonal antibody appears to be developmentally regulated, i.e., transiently expressed on younger, terminally differentiating oligodendrocytes. Among the cell lines studied, only two rat oligodendrocyte lineage cell lines showed surface reactivity with SCH 94.03. Western blotting of secondary isolated oligodendrocytes lysates revealed reactivity with multiple protein bands of 27, 32, 50, 100, and 106 kDa, whereas there was no reactivity to lipid antigens by immuno-thin layer chromatography. These results raise the possibility that SCH94.03 recognizes a novel oligodendrocyte-specific surface antigen, and may act directly on oligodendrocytes to promote remyelination.

Animals↗
PubMed1996

Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro.

Phosphorus retention is an important factor in the development of hyperparathyroidism secondary to renal failure. In vivo manipulation of phosphorus is associated with changes in serum calcium and calcitriol levels which in turn can modify parathyroid hormone synthesis and secretion. The present in vitro study evaluates whether high extracellular phosphorus has a direct effect on parathyroid hormone secretion. Fresh rat parathyroid glands were incubated in a media with phosphorus concentrations of 1, 2, 3, and 4 mM and subsequently exposed to calcium levels ranging from 0.4 to 1.35 mM. In 1.25 mM calcium, the parathyroid hormone secretion rate was similar in 1 and 2 mM phosphorus; however, a phosphorus concentration of 3 and 4 mM produced a 3- and 4-fold increase in the parathyroid hormone secretion, respectively, as compared with 1 mM phosphorus. While in 1 or 2 mM phosphorus an increase in calcium from 0.6 to 1.35 mM reduced parathyroid hormone secretion to 37%, in 4 mM phosphorus the same increase in calcium only inhibited parathyroid hormone secretion to 75%. Furthermore, the addition of arachidonic acid 20 microM, a substrate for inhibitory intracellular signal pathway, to the 4 mM phosphorus-1.35 mM calcium incubation media reduced the parathyroid hormone secretion to 34.5% (p < 0.05). In conclusion, our results indicate that in vitro, high phosphorus directly increases parathyroid hormone secretion.

Analysis of Variance↗
PubMed1996

Subacute encephalomyelitis presenting as stiff-person syndrome: clinical, polygraphic, and pathologic correlations.

A 60-year-old woman presented with stiff-person syndrome (SPS). Treatment with diazepam controlled her painful spasms initially. Two and one-half years after the onset of SPS, new spells of paroxysmal leg jerking and apnea developed. A spell was recorded with simultaneous video and polygraphic techniques that revealed simultaneous firing of motor unit potentials in several muscles (paraspinal, internal hamstring, and abdominal muscles). Apnea was associated with arterial oxygen desaturation. An increase in the dose of diazepam decreased the number and severity of these episodes. Seventeen months later, the patient began to taper the diazepam dose. Shortly thereafter, she had a cardiorespiratory arrest and subsequently died. Autopsy showed small chronic inflammatory foci in the pancreas (some associated with islets) and findings of diffuse encephalomyelitis characterized by perivascular cuffing in the spinal cord, brainstem, thalamus, hippocampus, and amygdala and a dense mononuclear infiltrate in the anterior horns of the lumbar and cervical cord, with relative preservation of axons and myelin. Cell typing showed this infiltrate was polyclonal and reactive. There have been rare cases of SPS associated with encephalomyelitis reported previously. Although the prolonged course in our patient suggested that SPS may have preceded encephalomyelitis, the more likely explanation is that the patient had an unusually long course of encephalomyelitis alone.

Brain↗
PubMed1996

Reduced hyperalgesia in nerve-injured WLD mice: relationship to nerve fiber phagocytosis, axonal degeneration, and regeneration in normal mice.

The pathogenesis of neuropathic pain states is influenced by inflammatory factors associated with nerve injuries and may be mediated in part by the macrophage-dependent process of Wallerian degeneration. Macrophages play a dominant role in the Wallerian (axonal) degeneration that characterizes the painful chronic constriction injury model of neuropathy by liberating proinflammatory cytokines at the site of nerve injury. These cytokines directly affect the structural integrity of neural systems and have been implicated in the development of hyperalgesic states. We hypothesized that interference with the pathologic process of Wallerian degeneration would alter the development of the neuropathic pain state. To test this hypothesis, we studied the development of thermal hyperalgesia in the chronic constriction injury model of neuropathy using normal mice and mice of the WLD strain in which recruitment of macrophages to the site of nerve injury and Wallerian degeneration are delayed. We compared the onset and magnitude of the hyperalgesia with quantitative measures of nerve injury including the phagocytic cellular activity associated with Wallerian degeneration. In C57BL/6J (6J) mice, hyperalgesia peaked 3-10 days after placement of the ligatures, qualitatively matching the response previously reported for rats. In C57BL/WLD (WLD) mice, there was reduced hyperalgesia temporally associated with reduced numbers of phagocytic cells in the injured nerve. In injured WLD nerves there was a reduced rate of axonal degeneration compared to similarly injured 6J nerves. Regeneration was correspondingly delayed in the WLD animals. The results suggest that the process of Wallerian degeneration is a key factor in the pathogenesis of hyperalgesia. Continued development of mouse models of neuropathic pain will be important in exploring the molecular basis of neuropathic pain. Interference with the cellular mediators of Wallerian degeneration may be a useful therapeutic strategy that might modulate the onset and magnitude of hyperalgesia following nerve injury.

Animals↗
PubMed1996

Spontaneous central nervous system remyelination in strain A mice after infection with the Daniel's (DA) strain of Theiler's virus.

Intracerebral infection of susceptible SJL/J (H-2s) mice with the Daniel's strain of Theiler's murine encephalomyelitis virus produces chronic, progressive, inflammatory central nervous system demyelination, with minimal spontaneous remyelination. To assess the role of host genetic factors in spontaneous myelin repair following chronic infection with the Daniel's strain of Theiler's virus, we examined demyelination and spontaneous remyelination in strain A mice after infection with Theiler's virus. We found that A.BY/SnJ (H-2a), and A.SW/SnJ (H-2s) mice all developed chronic demyelination with substantial spontaneous remyelination 90 days after infection. In the spinal cords of both A/J and A/WySnJ mice, one quarter of the total lesion area showed spontaneous remyelination, whereas in A.SW/SnJ mice, the extent of remyelination increased to two thirds of the total lesion area. The spontaneous remyelination seen in strain A mice was consistent with myelin repair by oligodendrocytes and Schwann cells, and occurred despite the presence of persistent virus antigen. These results indicate that host-pathogen interactions play an important role in myelin regeneration after virus-induced demyelination, and suggest that host genetic factors influence spontaneous remyelination.

Animals↗
PubMed1996

A monoclonal autoantibody which promotes central nervous system remyelination is highly polyreactive to multiple known and novel antigens.

A monoclonal antibody (mAb), designated SCH94.03, which promotes central nervous system remyelination in susceptible mice infected with Theiler's virus, has been proposed to be a natural autoantibody based on its germline immunoglobulin sequence. To identify the potential antigens recognized by mAb SCH94.03, a rat brain lambda gtll cDNA expression library was screened with this antibody. Nine independent clones were identified. Five clones were identical or highly similar to known cDNAs or proteins (rat kinesin light chain, mouse thrombospondin 1, mouse oncofetal antigen, RNA polymerase beta subunit and nuclear phosphoprotein). Four clones, designated REM#1, REM#2, REM#3 and REM#4, contained open reading frames, but were not homologous to any known genes or proteins. The reactivity of SCH94.03 with all nine clones was specific in that all nine clones identified contained continuous open reading frames and none of nine control IgM mAbs showed reactivity with any of the nine cDNA clones. The precise specificity of binding of mAb SCH94.03 was demonstrated by the absence of reactivity to the identified clones with IgM Ab from B cell lymphoma (CH12) which has identical cDNA sequences with mAb SCH94.03, but differ only in the heavy chain CDR3 N region. Our studies support the hypothesis that highly polyreactive natural autoantibodies can play a role in promoting central nervous system remyelination.

Actins↗
PubMed1996

Induction of ileum muscarinic cholinoceptor signal transduction pathways by rat interferon-gamma.

We have recently shown that rat interferon-gamma (IFN gamma) can trigger a cholinergic muscarinic response upon interaction with isolated rat atria, decreasing both the contractile tension and cAMP synthesis, and increasing cGMP production. Because the intestine is rich in cholinergic muscarinic receptors, and IFN gamma-producing cells are normal components of the mucosal immune system, we investigated whether IFN gamma could also modulate the muscarinic cholinergic activity of the intestine. Our results indicate that IFN gamma may interact with ileum cholinergic muscarinic receptors by inhibiting binding of the radiolabelled antagonist quinuclidinyl benzylate (3H-QNB), decreasing cAMP formation and increasing cGMP synthesis. These effects are associated with increased mechanical activity of the isolated ileum strips, and can be blunted by pretreatment of the tissue with atropine.

Animals↗
PubMed1996

Minor constituents of sabulous material in equine urine.

The secondary constituents accompanying calcite and vaterite (crystalline forms of calcium carbonate) in the sabulous deposits from 140 vesical samples and one renal sample of equine urine were studied by infrared spectroscopy (IR), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). Apatitic calcium phosphate, present in 12 per cent of the samples, generally appeared in the form of spherulites with smooth and rough surfaces. Calcium sulphate, clearly detected by IR in 12.7 per cent of the samples, did not have a characteristic structure under SEM, although EDX detected sulphur in the samples. Amorphous silica was observed in one case and had a nodular appearance. Organic fibres were not as common as might have been expected in equine urinary deposits.

Animals↗
PubMed1996

[Analysis of pediatric home care services of the Assistance Publique--Hôpitaux de Paris].

BACKGROUND: The Home Health Care services for children in Paris was recently established and it is interesting to analyse the first results of their activities. POPULATION AND METHODS: A random sample (n = 157) of the 418 children admitted to home health care in the Assistance publique-Hôpitaux de Paris (HAD-P) in 1991 has been studied; only one episode of care was analyzed for each child. The data analysed included sociodemographic characteristics of the children, their clinical diagnosis and the care received. RESULTS: More than half of the children presented chronic diseases. Follow-up of newborn children was the main reason for admitting children with acute conditions. Housing and socioeconomic conditions were poor for a significant number of children. A seasonal pattern was found, with higher activity in the beginning and in the end of the year. CONCLUSIONS: More efforts are needed to develop complementarity between hospital-based and home health care services, beginning with improved communication of detailed information regarding home health care objectives and conditions.

Acute Disease↗
PubMed1996

Relative effects of PTH and dietary phosphorus on calcitriol production in normal and azotemic rats.

In moderate renal failure, the serum calcitriol level is influenced by the stimulatory effect of high PTH and the inhibitory action of phosphorus retention. Our goal was to evaluate the relative effect that high PTH levels and increased dietary phosphorus had on calcitriol production in normal rats (N) and rats with moderate renal failure (Nx). Normal and Nx (3/4 nephrectomy) rats were divided into two groups: (1) rats with intact parathyroid glands (IPTG) and (2) parathyroidectomized rats in which PTH was replaced (PTHR) by the continuous infusion of rat 1-34 PTH, 0.022 microgram/hr/100 g body wt, using a miniosmotic Alzet pump. To test the effect of dietary phosphorus, rats received either a moderate (MPD, 0.6% P) or a high phosphorus (HPD, 1.2%) diet for 14 days. The experimental design included pair-fed N and Nx rats with either IPTG or PTHR. Serum calcitriol and PTH levels in N rats fed a MPD were 69 +/- 3 and 40 +/- 5 pg/ml, respectively. In Nx rats on a MPD, serum calcitriol levels decreased only if hyperparathyroidism was not allowed to occur (76 +/- 4 vs. 62 +/- 4 pg/ml in Nx-IPTG-MPD and Nx-PTHR-MPD groups respectively, P < 0.05). Even in N rats on a HPD, high PTH levels (67 +/- 8 pg/ml in the N-IPTG-HPD group) were required to maintain normal serum calcitriol levels (69 +/- 4 vs. 56 +/- 6 pg/ml in Nx-IPTG-HPD and Nx-PTHR-HPD groups, respectively; P < 0.05). In Nx rats on a HPD, the development of secondary hyperparathyroidism (286 +/- 19 pg/ml in the Nx-IPTG-HPD group) prevented a decrease in serum calcitriol levels (68 +/- 7 pg/ml). In contrast, serum calcitriol levels were low in the Nx-PTHR-HPD group (52 +/- 4 pg/ml, P < 0.05), which were deprived of the adaptative increase in endogenous PTH production. In conclusion, our results in rats indicate that in moderate renal failure, an elevated PTH level maintains calcitriol production and overcomes the inhibitory action of phosphorus retention.

Animals↗
PubMed1996

The set point of calcium and the reduction of parathyroid hormone in hemodialysis patients.

Since in some studies in hemodialysis patients calcitriol treatment has resulted in a reduction of both parathyroid hormone (PTH) levels and the set point of calcium, it has been suggested that that the set point of calcium reflects a reduction in the magnitude of hyperparathyroidism. However, others have maintained that the set point of calcium is primarily an indicator of the serum calcium at which PTH is secreted and may be dissociated form the magnitude of hyperparathyroidism. The present study was designed to evaluate how a reduction in PTH levels associated with an increase in the predialysis (basal) serum calcium would affect the set point of calcium. Two different treatments were used to produce a reduction in PTH that was associated with an increase in predialysis serum calcium. In the first group, hemodialysis patients received 2 micrograms of intravenous calcitriol and were dialyzed with a 3.5 mEq/liter calcium dialysate for six weeks; in the second group, hemodialysis patients were dialyzed with a 4 mEq/liter calcium dialysate and had oral calcium supplementation increased for six weeks. In both groups, low and high calcium studies were performed to determine the PTH-calcium relationship before treatment, at the end of six weeks of treatment, and six weeks after the discontinuation of treatment. In the calcitriol group the predialysis calcium increased form 9.62 +/- 0.34 to 10.56 +/- 0.31 mg/dl, P < 0.05 and the set point of calcium increased from 9.34 +/- 0.23 to 9.79 +/- 0.25 mg/dl, P < 0.05 at the same time as maximally stimulated PTH decreased from 2637 +/- 687 to 1555 +/- 617 pg/ml, P < 0.05. In the high calcium dialysate group, the predialysis serum calcium increased from 9.19 +/- 0.31 to 9.84 +/- 0.28 mg/dl, P < 0.05, and set point of calcium increased form 9.01 +/- 0.28 to 9.39 +/- 0.22 mg/dl, P < 0.05 at the same time as maximally stimulated PTH decreased from 1642 +/- 450 to 1349 +/- 513 pg/ml, P < 0.05. Discontinuation of treatment for six weeks resulted in a return to pretreatment values. In conclusion, our results would suggest that (1) the set point of calcium may not be a reliable indicator of the magnitude of hyperparathyroidism during calcitriol treatment, and (2) PTH secretion may adapt to the ambient serum calcium concentration.

Adult↗
PubMed1996

An ideR mutant of Mycobacterium smegmatis has derepressed siderophore production and an altered oxidative-stress response.

The mycobacterial ideR protein is a homologue of the diphtheria-toxin repressor DtxR. We have previously demonstrated that Mycobacterium tuberculosis ideR, like DtxR, represses transcription of Corynebacterium diphtheriae iron-regulated promoters in vivo and binds to C. diphtheriae operators in a metal-dependent manner in vitro. We show here that ideR mutants of M. smegmatis, constructed by allelic replacement, were defective in their ability to repress siderophore biosynthesis in the presence of iron. They were also more sensitive to hydrogen peroxide and had decreased levels of catalase/peroxidase (KatG) and manganese superoxide dismutase (Mn-SOD). This indicates that ideR is a negative regulator of siderophore production and is required for the response to superoxide- and hydrogen peroxide stress. We propose that ideR is the mycobacterial counterpart of the Escherichia coli Fur protein, i.e. It is a pleiotropic regulator that couples iron metabolism to the oxidative-stress response.

Alleles↗
PubMed1996

A monoclonal natural autoantibody that promotes remyelination suppresses central nervous system inflammation and increases virus expression after Theiler's virus-induced demyelination.

We have used an established experimental model of multiple sclerosis to investigate the potential beneficial relationship between natural autoimmunity and remyelination after central nervous system (CNS) demyelination. Intracerebral infection of SJL/J mice with Theiler's murine encephalomyelitis virus (TMEV) produces chronic, progressive, inflammatory CNS demyelination. Chronically infected SJL/J mice show minimal spontaneous remyelination, which is in part due to a T cell-mediated immune response inhibiting myelin repair. We previously identified a monoclonal natural autoantibody, designated SCH94.03, that promotes remyelination when passively transferred to chronically infected SJL/J mice. The mechanism whereby SCH94.03 promotes remyelination is unknown, although previous reports suggest that natural autoantibodies can modulate immune system function. In this report we demonstrate that treatment with SCH94.03 reduced by 2- to 3-fold the number of CD4(+) and CD8(+) cells infiltrating the CNS of SJL/J mice chronically infected with TMEV, in the absence of global lymphocyte depletion. Associated with the decreased inflammation was a 2- to 3-fold increase in virus antigen expression without a significant increase in viral RNA or virus titers. Treatment with SCH94.03 also suppressed the humoral immune response to a T cell-dependent antigen in chronically infected mice. Immunohistochemical staining showed that SCH94.03 labeled MHC class II-positive dendritic cells in peripheral lymphoid organs. These results are consistent with the proposed immunomodulatory function of natural autoantibodies and suggest that one mechanism whereby SCH94.03 promotes CNS remyelination in chronically infected SJL/J mice is through inhibition of a pathogenic immune response.

Animals↗