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Biomedical subjects

R G Feldman

Publications and source records attributed to R G Feldman.

At least 19 recordsLinked to original sources
PubMed1996

The assessment of neurobehavioral toxicity: SGOMSEC joint report.

Exposure to neurobehavioral toxicants is a problem of international scope. Although many different procedures are available for the assessment of human behavioral function, performance tests are displacing traditional diagnostic tests for ascertaining the consequences of exposure to neurotoxic chemicals. Performance testing includes variables such as attention and concentration, sensory function, motor control, spatial relations, visuomotor coordination, memory, and affect. Special tests have also been devised for evaluating child development. One of the salient needs in these efforts is the construction of databases allowing access to normative data.

Adult↗
PubMed1995

Neurobehavioral effects of acute and chronic mixed-solvent exposure in the screen printing industry.

This 2-year prospective study examined the neurobehavioral effects of acute and chronic exposure to mixed solvents in workers in a screen printing business. A total of 30 subjects participated in the study in two field testings over a 12 month period. Each subject completed a detailed medical and occupational questionnaire, had a neurological examination, and underwent a battery of neuropsychological tests. Industrial hygiene investigation identified the following chemical exposures as present: toluene, methyl ethyl ketone, mineral spirits, beta-ether, methylene chloride, and acetic acid. Different departments and jobs had varying degrees of exposure to these chemicals, the highest exposures being in the ink mix area and the screen washroom area. However, all exposure levels were below recommended threshold limit values. Persons categorized as having higher acute exposure demonstrated significantly impaired test performance on tasks involving manual dexterity, visual memory, and mood. Those with higher chronic exposure demonstrated significantly poorer performance on visual memory tasks and mood. Results suggest that the mixed solvents used in the screen printing industry have an effect on central nervous system functioning in the absence of obvious clinical disease.

Adult↗
PubMed1995

Anti-polysaccharide immunoglobulin isotype levels and opsonic activity of antisera: relationships with protection against Streptococcus pneumoniae infection in mice.

Relationships between in vitro parameters (opsonic activity and anti-pneumococcal polysaccharide [PS] antibody subclasses) and in vivo mouse protection were established by logistic regression analysis. Data were from 158 mice challenged with pneumococci after vaccination with synthetic oligosaccharide- and PS-protein conjugates in combination with the adjuvant Quil A. The hypothesis that serum opsonic activity has predictive value for protection against pneumococcal infection was tested. Serum opsonic activity was well correlated with protection (chi 2 = 35.5, P < 0.001), although a stronger correlation was observed for anti-PS IgM and IgG. The combined use of IgG and opsonic activity as predictor variables yielded the best fitting model for predicting protection (chi 2 = 74.1, P < 0.001). When opsonic activity data were added to models that included various antibody isotypes, the statistical significance of the models was enhanced. Thus, the opsonic activity of antisera induced by pneumococcal vaccines can predict mouse protection.

Adjuvants, Immunologic↗
PubMed1995

Human immunoglobulin G (IgG) Fc receptor IIA (CD32) polymorphism and IgG2-mediated bacterial phagocytosis by neutrophils.

Human immunoglobulin G (IgG) Fc receptor IIa (Fc gamma RIIa; CD32) is expressed on phagocytes, triggers phagocytosis, and represents the sole Fc receptor for IgG (Fc gamma R) capable of interaction with IgG2, the main IgG subclass induced in response to bacterial capsular polysaccharides. The two genetically determined structurally different allotypes of human Fc gamma RIIa, the products of the Fc gamma RIIa-R131 and IIa-H131 alleles, have functionally different reactivities with human IgG2. In humans, the Fc gamma RIIa-H131 allotype is known to interact efficiently with complexed human IgG2, whereas the IIa-H131 allotype does so only poorly. This polymorphism may therefore have implications for IgG2-mediated phagocytosis of encapsulated bacteria and susceptibility to bacterial infections. Phagocytosis of IgG2-opsonized bacteria by homozygous Fc gamma RIIa-R/R131, heterozygous IIa-H/R131, and homozygous IIa-H/H131 polymorphonuclear cells (PMN) was compared. A higher phagocytic capacity of IgG2-opsonized group B type III streptococci by PMN of homozygous H/H131 individuals compared with PMN from homozygous R/R131 individuals was observed (P = 0.001), while heterozygous IIa-H/R131 PMN showed intermediate phagocytosis. In this model system, IgG2-mediated phagocytosis was independent of the Fc gamma RIIIb-NA1/NA2 allelic polymorphism.

Antigens, CD↗
PubMed1994

Solid-phase antigen density and avidity of antibodies detected in anti-group B streptococcal type III IgG enzyme immunoassays.

Two enzyme immunoassays which measure anti-group B streptococcal type III capsular carbohydrate IgG antibodies were compared. One utilised poly-L-lysine conjugated coating antigen while the other used tyraminated coating antigen. Both carbohydrate antigens appeared to be antigenically identical but the poly-L-lysine based assay gave significantly lower values for some sera. Sera were identified which had low and high avidity anti-group B streptococcal type III IgG antibodies by the thiocyanate elution method. These antibodies gave results on a dilution range of coating concentrations consistent with their relative avidity. Comparison of dilution ranges of the two conjugates used for coating suggests that the poly-L-lysine conjugate coats with a ten-fold lower efficiency than the tyramine conjugate and therefore detects only higher avidity antibodies. Four fractions containing different relative avidities of affinity-purified IgG were produced from a single serum. These fractions behaved in the same manner as sera containing antibodies of different avidities. The results of this study suggest that the method of polysaccharide conjugation in enzyme immunoassays may affect the antigen concentration on the solid phase and thence the detection of antibodies of various avidities.

Antibodies, Bacterial↗
PubMed1994

Epitope specificity of rabbit immunoglobulin G (IgG) elicited by pneumococcal type 23F synthetic oligosaccharide- and native polysaccharide-protein conjugate vaccines: comparison with human anti-polysaccharide 23F IgG.

Streptococcus pneumoniae type 23F capsular polysaccharide (PS23F) consitss of a repeating glycerol-phosphorylated branched tetrasaccharide. The immunogenicities of the following related antigens were investigated: (i) a synthetic trisaccharide comprising the backbone of one repeating unit, (ii) a synthetic tetrasaccharide comprising the complete repeating unit, and (iii) native PS23F (all three conjugated to keyhole limpet hemocyanin [KLH]) and (iv) formalin-killed S. pneumoniae 23F. All antigens except the trisaccharide-KLH conjugate induced relatively high anti-PS23F antibody levels in rabbits. The epitope specificity of such antibodies was then studied by means of an inhibition immunoassay. The alpha(1-->2)-linked L-rhamnose branch was shown to be immunodominant for immunoglobulin G (IgG) induced by tetrasaccharide-KLH, PS23F-KLH, and killed S. pneumoniae 23F: in most sera L-rhamnose totally inhibited the binding of IgG to PS23F. Thus, there appears to be no major difference in epitope specificity between IgG induced by tetrasaccharide-KLH and that induced by antigens containing the polymeric form of PS23F. Human anti-PS23F IgG (either vaccine induced or naturally acquired) had a different epitope specificity: none of the inhibitors used, including L-rhamnose and tetrasaccharide-KLH, exhibited substantial inhibition. These observations suggest that the epitope recognized by human IgG on PS23F is larger than the epitope recognized by rabbit IgG. Both human and rabbit antisera efficiently opsonized type 23F pneumococci, as measured in a phagocytosis assay using human polymorphonuclear leukocytes.

Animals↗
PubMed1993

Trimethyltin encephalopathy.

A chemistry student was acutely exposed to vapors of an organotin compound. Seventy-two hours later, he exhibited delirium, spatial disorientation, perseveration, inappropriate affect, and memory defects. Five months later, he experienced episodes of complex partial seizures, which continue to require anticonvulsant medication after 7 years. Trimethyltin was identified in blood and urine samples taken 17 days after the accident; the blood level of trimethyltin was elevated 35 days after exposure. Serial electroencephalograms showed persistent left temporal paroxysmal epileptogenic potentials. Serial neuropsychological tests revealed persistent memory defects, cognitive dysfunction, and dysphoria 4 years after exposure. We review acute, resolving, and long-term residual neurotoxic effects of trimethyltin in man. We describe detailed clinical observations, serial neuropsychological test results, electroencephalographic findings, and exposure data in this patient, confirming the limbic system effects of trimethyltin and relating them to the known histopathologic pattern of this condition.

Accidents, Occupational↗
PubMed1993

Magnetic resonance imaging (MRI), neurobehavioral testing, and toxic encephalopathy: two cases.

The objective of this investigation was to examine cerebral magnetic resonance imaging (MRI) pathology and functional deficits demonstrated by neuropsychological testing in cases of toxic encephalopathy. Two subjects, occupationally exposed to toxic chemicals, were studied. As part of their neurological assessment, MRI was done and each underwent a neuropsychological battery for patients with toxic exposures (White et al. Clin. Neuropharmacol. 13(5), 392-412, 1990). In Case 1, who was exposed to inorganic mercury, MRI showed mild central and cortical atrophy. Punctiform foci (T2) were noted in both frontal regions underlying the precentral gyri and in the subcortical myelin. Neuropsychological testing showed problems in cognitive flexibility, cognitive tracking, inhibiting perseveration, fine manual motor coordination, visuospatial analysis and organization, memory, and affect and personality. In Case 2, who was exposed to 2.6-dimethyl-4-heptanone, MRI showed multiple small foci in the white matter and pons. Neuropsychological testing indicated affective changes, deficits in manual motor speed, verbal fluency, visuospatial organization, and short-term memory. Lack of aphasia in patients with toxic encephalopathy indicates that neurotoxins probably affect subcortical and mesial temporal structures more than cortical gray matter. These MRI studies show subcortical sites of pathology.

Behavior↗
PubMed1993

Human B lymphocyte in vitro response to the group B streptococcal type III capsular carbohydrate.

Anti-group B streptococcal type III polysaccharide-specific human B cells from the peripheral circulation can be activated and detected in an in vitro culture system. It is possible to detect both IgM- and IgG- producing cells from both seropositive and seronegative donors. The specificity of the response was demonstrated by inhibition with excess liquid phase antigen and the use of related but antigenically distinct control antigens. The response was absent without the addition of T cells, optimal at 10% and 25% T cells respectively for IgM- and IgG-secreting cells, and undetectable using 50% T cells. The optimal antigen concentration for in vitro B-cell activation is 2.5 x 10(-4) micrograms/ml. Cells from 5 of 6 seropositive donors and 3 of 7 seronegative donors produced specific IgM antibody after culture with antigen. We conclude that the control of the human antibody response to the group B streptococcal type III polysaccharide is influenced by T cells. The response seen in the culture system may be of value in assessing future vaccine candidates designed to prevent neonatal infections.

Antibodies, Bacterial↗
PubMed1993

Age influences magnitude but not duration of response to levodopa.

Following an all-night fast, 45 patients with Parkinson's disease were examined using certain motor items present in the United Parkinson's Disease Rating Scale. All were given a single tablet of carbidopa 25 mg and levodopa 250 mg and re-examined 90 minutes later. In addition to this evaluation, 23 of these patients underwent further scoring over a 4-hour period. A significant negative correlation was found between age and one important aspect of drug-derived benefit: magnitude of response. In contrast, age had no apparent influence on duration of benefit from the drug. Although baseline (fasting) scores were predictably correlated with duration of disease, magnitude of response was not adversely influenced by this variable. Not all Parkinsonian signs were equally influenced by age. Whereas the poor response of gait and bradykinesia appeared to be dependent on age, no such effect was noted on rest tremor scores. The data indicate that in patients with Parkinson's disease treated long term, factors associated with age rather than duration of disease may have a stronger adverse influence on magnitude of response to levodopa.

Adult↗
PubMed1992

Blink reflex measurement of effects of trichloroethylene exposure on the trigeminal nerve.

Trichloroethylene (TCE) exposure is known to have specific toxic effects on cranial nerves, the trigeminal nerve (V) in particular. The electrophysiological measurement of the blink reflex (BR) can quantify latency changes in the Vth and VIIth cranial nerve reflex arc. Prior study looked at the blink reflex measurement in a community group exposed to TCE in their drinking water. This study evaluated the use of the electrophysiologic blink reflex as an indicator of neurotoxic effects of TCE in occupationally exposed workers. The BR was tested in individual cases with documented histories of exposure to known chemical neurotoxins including TCE (n = 18). When compared with the nonexposed laboratory control values (n = 30), the subjects with a significant history of TCE exposure demonstrated the most prolonged latencies (greater than or equal to 3.0 SD above the nonexposed group mean) in the R1 component of the blink reflex measurement. The electrophysiological study of the blink reflex has application in assessing TCE exposure and in documenting the neurotoxic effects of that exposure on trigeminal nerve functions in humans.

Adult↗
PubMed1992

A perceived cluster of amyotrophic lateral sclerosis cases in a Massachusetts community.

We investigated a report of a perceived cluster of amyotrophic lateral sclerosis (ALS) in Middleborough, Mass. Although an increase in ALS incidence was observed [2.51 deaths/100,000 person-years (p-y)], relative to the statewide rate over the years 1969-1985 (1.26/100,000 p-y), it was not statistically significant at the 95% confidence level. Problems in evaluating possible neurological disease clusters and their association with environmental exposures are presented.

Adult↗
PubMed1992

Lead neurotoxicity and disorders of learning.

Preventable and treatable causes of disorders of learning caused by lead exposure can be recognized by heightened awareness of this potential hazard. The Centers for Disease Control using data from many studies of neurobehavioral effects of lead in children and animals, has redefined the lead exposure threshold for clinical and social intervention from 25 micrograms/dL to 10 micrograms/dL. This article reviews the pertinent studies that provide evidence of the effects of lead exposure on development of the nervous system, effects on neural structures involved in memory and learning, and the impact of early lead encephalopathy on adolescent and adult learning skills and cognitive performance. Physicians, teachers, and child care personnel are responsible for identifying children with behavioral signs of subclinical lead intoxication as early as possible. Screening programs and preventive strategies, such as the multitier Centers for Disease Control approach referred to in this article, are necessary. It is no longer reasonable to assume that lead-exposure children not demonstrating severe encephalopathy will recover completely, without residual brain damage after removal from exposure. Sufficient evidence now exists to clearly demonstrate measurable effects of low levels of lead body burden on behavioral and intellectual performance, resulting in learning disorders.

Child↗