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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
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↗
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↗
PubMed1992

Abnormalities in color vision and contrast sensitivity in Parkinson's disease.

Dopamine is a neurotransmitter found in the retina. Delays in the visual evoked responses and abnormalities in contrast sensitivity occur in patients with Parkinson's disease. Improvement in the P100 has followed L-dopa therapy. Suspected abnormalities at the retinal level in Parkinson's disease are observed in reductions in photopic, scotopic, and pattern-derived electroretinograms. We studied 35 patients with Parkinson's disease and 26 controls of comparable age and visual acuities using visual evoked responses, color vision, and contrast sensitivity testing. Contrast sensitivity thresholds were significantly different at most frequencies tested, using both stationary and temporally modulated sinusoidal gratings. The total error score of the Farnsworth-Munsell 100 Hue Test revealed significant differences between the patients and controls. The contrast thresholds derived from certain spatial frequencies and the total error in color score were significantly related to the duration of disease. A stepwise discriminant analysis correctly identified 94% of the patients and 94% of the controls. The significant error in chromatic discrimination observed in Parkinson's disease patients may be due to altered intraretinal dopaminergic synaptic activity in these patients.

Color Perception↗
PubMed1991

Hippocampal lesions in dominantly inherited Alzheimer's disease.

We compared hippocampal lesions in three pedigrees of Familial Alzheimer's Disease (FAD). In these pedigrees, the disease is inherited as an autosomal dominant disorder and has been linked to DNA markers on chromosome 21. In eight cases of FAD (four from one pedigree and two each from two others) we quantified neurofibrillary tangles (NFT) and senile plaques (SP) in hippocampal subdivision CA1-4, subiculum, presubiculum, and dentate gyrus. We observed consistent patterns of the distribution of lesions: The highest density of NFT and SP was present in CA1-2; virtually no SP or NFT were present in presubiculum; SP diameter was consistently greatest in CA4. We found no overall differences among pedigrees in total densities of NFT and SP, but statistical analyses disclosed that an uncommon type of SP was disproportionately present in two pedigrees. This type of SP was usually restricted to CA4, had a marked amyloid core devoid of argyrophilic neurites. These studies also disclosed inter- and intrafamilial heterogeneity of lesion distribution (including congophilic angiopathy and cerebellar plaques) in these three pedigrees.

Alzheimer Disease↗
PubMed1990

Relation of distribution of conduction velocities to nerve biopsy findings in n-hexane poisoning.

Distribution of conduction velocities (DCV) of sensory fibers in sural nerve was investigated in three patients with n-hexane poisoning. Measurements were made at 1-2 months, 4-9 months, and at 11, 23, and 36 months after ending exposure. A sural nerve biopsy was obtained from one of the patients. The results indicated the characteristic changes of n-hexane toxicity: myelinated nerve fiber degeneration and paranodal swelling, resulting in changes in the fiber diameter distribution. The DCV documented these changes. After removal from toxic exposure, varying degrees of recovery were studied clinically and evaluated with nerve conduction parameters. The DCV reflects the pathological changes in nerve in toxic neuropathy due to n-hexane.

Adult↗
PubMed1990

Immunoglobulin prophylaxis for infants exposed to varicella in a neonatal unit.

The investigation and prophylaxis with anti-varicella-zoster immunoglobulin (ZIG) of 15 preterm infants (24-33 weeks gestation and 1-300 days postnatal age) exposed to varicella on a neonatal intensive care unit are described. Varicella-zoster virus (VZV) IgG was detectable in 13 infants (24-28 weeks gestation) less than 105 days of age and born to seropositive mothers. Current guidelines recommend ZIG for all preterm infants of less than 28 weeks gestation following exposure to VZV. Our findings suggest that ZIG need be given only to seronegative infants or infants of seronegative mothers and to those over 60 days postnatal age.

Antibodies, Viral↗
PubMed1990

Environmentally related disorders of the nervous system.

Specific physical and chemical agents found in the workplace and in the general environment are responsible for characteristic pathologic processes within the nervous system. It has been shown that many neurotoxic agents produce a dose-related spectrum of impairment ranging from mild slowing of nerve conducting velocity or prolongation in reaction time to neuropathy and frank encephalopathy. Clinical manifestations are determined by the agent involved, by the dose of exposure, the vulnerability of the cellular target, the ability of the organism to metabolize and excrete the agent, and the ability to repair damage. An occupational history, including evaluation of evidence of specific agents and job history, is a critical component in the clinical management of individuals with suspect neurotoxic disease. Environmentally-induced disorders can be prevented by appropriate environmental controls. Prevention of neurotoxic disease is a complex process requiring continuous involvement of public health agencies and strong scientific research.

Central Nervous System Diseases↗
PubMed1990

Prevalence of anti-group B streptococcal type III capsular IgG antibodies in the United Kingdom and an analysis of their specific IgG subclasses.

Neonatal infection due to group B streptococcus (GBS) has a higher incidence in the USA than in the United Kingdom. A British population was investigated to ascertain the proportion of women who have protective anti-GBS type III IgG levels. Thirty-one (34%) of 90 pregnant women, 10 (43%) of 23 nonpregnant women, and 5 (50%) of 10 mothers of healthy colonized infants had anti-type III IgG greater than or equal to 2 micrograms/ml. Of 19 mothers who had infants infected with GBS type III, 17 (89%) had low specific IgG levels; of the other 2, the infants themselves had low IgG levels. The proportion of women in the UK with protective antibody levels is higher than in the USA. Sera (12) were assayed for anti-type III IgG isotypes; all contained IgG2, 6 had detectable IgG1, and 1 had IgG4.

Antibodies, Bacterial↗