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Biomedical subjects

J L Benach

Publications and source records attributed to J L Benach.

At least 55 records · Page 3Linked to original sources
PubMed1992

Selection of an escape variant of Borrelia burgdorferi by use of bactericidal monoclonal antibodies to OspB.

Two immunoglobulin G (IgG) monoclonal antibodies (MAbs) to outer surface protein B (CB2 and CB6), affinity purified from mouse ascitic fluid, exhibited concentration-dependent inhibitory and bactericidal properties against Borrelia burgdorferi after a 24-h incubation period in spirochete medium. Fab fragments derived from these MAbs showed the same effects, indicating that they were not caused by agglutination of the organisms by the intact MAbs. The inhibition of spirochete growth in cultures containing MAbs was also detected by spectrophotometric analysis of the media. CB2 did not inhibit the growth of Borrelia hermsii or the BEP4 strain of B. burgdorferi, neither of which is recognized by the MAb. Affinity-purified IgG from hybridoma supernatants had similar effects on B. burgdorferi as the ascitic-fluid-derived IgG did, indicating that the inhibitory and bactericidal properties were not due to nonspecific toxic contaminants. The bactericidal properties of the MAbs were not complement dependent as there was none in the serum-free system. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of B. burgdorferi organisms surviving after exposure to CB2 revealed an escape variant which failed to express OspB. The continued presence of OspA in these escape variants indicates that the lack of OspB was not due to the loss of the plasmid which contains the genes for both of these proteins.

Animals↗
PubMed1992

Borrelia burgdorferi and other related spirochetes bind to galactocerebroside.

Spirochetes are agents of neurologic disease that may utilize specific neural cell surface molecules for adhesion. Borrelia burgdorferi, the etiologic agent of Lyme disease, bound to galactocerebroside (GalCer) in numbers that were two- to threefold greater than to ceramide and glucocerebroside, and four- to fivefold greater than to sphingosine, psychosine, sulfatide, cholesterol, and three membrane phospholipids. The adherence was greater to GalCer and ceramide with a higher content of alpha-hydroxyl fatty acids. Treponema phagedenis Reiter and Borrelia hermsii also bound to GalCer. The binding of B burgdorferi to GalCer was inhibited in a concentration-dependent manner by rabbit polyclonal and murine monoclonal antibodies to this glycosphingolipid component of myelin. The monoclonal antibody to GalCer also inhibited adhesion of the organisms to Schwann cells. Neither free D or L monosaccharides nor the lectin peanut agglutinin inhibited binding. Since B burgdorferi and other spirochetes cause neurologic disease, these results suggest a role for GalCer as a binding site in both the central and peripheral nervous systems.

Animals↗
PubMed1991

The geographic spread and temporal increase of the Lyme disease epidemic.

OBJECTIVE: To describe the temporal and geographic progression of the Lyme disease epidemic in New York State from 1977 through 1989. DESIGN: Communicable disease surveillance system. SETTING: Statewide. MAIN OUTCOME MEASURES: The progression of the epidemic was examined by analyzing trends in Lyme disease cases reported to the state surveillance system, town and county Lyme disease incidence rates, Lyme disease hospital discharge rates, and the distribution of Ixodes dammini ticks obtained from surveillance efforts and submitted for identification. MAIN RESULTS: The number of confirmed Lyme disease cases in New York has increased with concurrent increases in the number of hospital discharges. The number of counties endemic for Lyme disease increased from four to eight between 1985 and 1989. The number of counties with documented I dammini ticks increased from four in 1985 to 22 in 1989. Incidence of the disease also increased within known endemic counties. CONCLUSIONS: Tick surveillance indicated that the range of I dammini has expanded annually into areas up to 384 km from the original known endemic areas of Long Island, NY, and Connecticut. Cumulative data from human surveillance resources document both temporal increases and geographic expansion of the Lyme disease epidemic in New York.

Adolescent↗
PubMed1991

Cytotoxicity of Borrelia burgdorferi for cultured rat glial cells.

A cytotoxic effect, as measured by 51Cr release, was detected after a 6-h incubation with two strains of Borrelia burgdorferi with neonatal rat primary brain cultures and with astroglial enriched cultures derived from the primary rat brain cells. A low-passage strain, J31, induced a significantly greater cytotoxic effect than did strain B31 in long-term in vitro culture. Live spirochetes and sonicates of both strains induced cytotoxicity, whereas heat-killed organisms did not. The degree of injury was greater in the primary brain than in the astroglial enriched cultures. Scanning electron microscopy revealed marked contraction of the membrane sheets and bleb production by the oligodendroglia of primary brain cultures after incubation with B. burgdorferi. The astroglial layer appeared unharmed.

Animals↗
PubMed1991

Cytokines and the pathogenesis of neuroborreliosis: Borrelia burgdorferi induces glioma cells to secrete interleukin-6.

Lyme disease is a multisystemic disease caused by a tickborne spirochete, Borrelia burgdorferi. Neuroborreliosis is characterized by intrathecal production of antibodies specific for the spirochete. This suggests that spirochetal infection of the central nervous system produces conditions that support the maturation of B lymphocytes to immunoglobulin-secreting cells. Interleukin 6 (IL-6) stimulates B cell differentiation into antibody-secreting cells. The present study was undertaken to determine whether B. burgdorferi can stimulate cells of central nervous system origin to secrete IL-6. C6 rat glioma cells cultured with spirochetes induced secretion of IL-6 activity. Peak stimulation was achieved at 24 h with 25 spirochetes per glioma cell. Glioma cells were also stimulated to produce IL-6 by interleukin 1 and tumor necrosis factor. That very few spirochetes are found in Lyme disease patients suggests that biologic amplification factors derived from the organism or the host, or both, are responsible for the pathogenesis of this disease. IL-6 can now be added to the growing list of such factors.

Animals↗
PubMed1991

Lyme borreliosis: host responses to Borrelia burgdorferi.

The chronic inflammatory condition that develops after infection by B. burgdorferi is a complex process resulting from host responses to a limited number of organisms. Amplification mechanisms driven by potent proinflammatory molecules, i.e., IL-1, may explain the vigorous response to a paucity of organisms. Spirochete dissemination to distant locations involves adherence to and penetration across endothelium and may be facilitated by host responses that increase vessel permeability. The apparent lack of tissue tropism in Lyme disease is reflected in the organism's ability to adhere to different eucaryotic cell types in vitro and the wide distribution of B. burgdorferi in various organs of infected humans and experimentally infected animals. While phagocytosis and complement activation have been observed in vitro, the specific immune response that develops in humans is inefficient in eradicating the organisms, which may possess some mechanism(s) to evade this response. There is significant evidence for host autoreactivity based on antigenic cross-reactivity between the 41-kDa flagellar subunit and stress proteins of the spirochetes and endogenous host cell components. Although the outer surface proteins appear to be suitable candidates as targets for vaccination in animal studies, fundamental differences in the immune response to spirochetal components may preclude their use in humans.

Animals↗
PubMed1991

Salivary gland antigens of Ixodes dammini are glycoproteins that have interspecies cross-reactivity.

Serum from rabbits and rats exposed to Ixodes dammini adults and larvae, respectively, contain antibodies to a large number of antigens in salivary gland homogenates from adult ticks that cross react with the antigens of a closely related species, Ixodes scapularis, and significantly with Dermacentor variabilis antigens. The salivary gland antigens of I. dammini are glycoproteins composed of both N- and O-linked carbohydrate chains. The antigenic determinants reside in both the polypeptide and carbohydrate chains.

Animals↗
PubMed1991

Lyme borreliosis: non-specific interactions of the organism with the host.

This article will review the known factors which are host derived or borne out of the interaction between Borrelia burgdorferi and the cells of the various organ systems in order to understand the process of infection B. burgdorferi as an arthropod-borne pathogen must adapt to various and diverse environments in its life cycle. In the invertebrate vector, this organism must tolerate the conditions of the tick midgut as well as the conditions after systemic dissemination. In the vertebrate host, this organism which resides initially in the skin, spreads hematogenously to the heart, brain, joints, and possibly to other tissues as well. At each site of infection, this organism must survive to induce the chronic course of illness characteristic of Lyme borreliosis. Evidence will be presented for the adhesion of B. burgdorferi to cells of diverse origins which suggests that the initiation of cellular injury may lack specificity. Other host non-specific responses will be reviewed.

Animals↗
PubMed1990

[Multiple sclerosis or Lyme disease? a diagnosis problem of exclusion].

There is no diagnostic biological marker in multiple sclerosis. Thus, its diagnosis is based on clinical criteria. These criteria can also be found in other conditions. Lyme disease is currently among them. In a late period of the disease demyelinating involvement of central nervous system can develop, and multiple sclerosis can be erroneously diagnosed. We have evaluated a series of 55 patients with a definite diagnosis of multiple sclerosis, and we have found evidence of infection by the causative organism of Lyme disease in three. We describe the three patients and we discuss the relationship between both conditions. We conclude that it is important to consider Lyme disease as a diagnostic possibility in patients with neurological disease of unknown etiology such as multiple sclerosis.

Adult↗
PubMed1990

Isolation, preliminary chemical characterization, and biological activity of Borrelia burgdorferi peptidoglycan.

Peptidoglycan (PG), an essential cell wall polymer of most bacteria, has been isolated from many species of spirochetes. Our interest in the host response to Borrelia burgdorferi led us to isolate and characterize its PG. Extracted cells were solubilized with warm 1% SDS followed by digestion with proteases. Amino acid analysis of the isolated PG demonstrated the presence of alanine, glycine, glutamic acid, and ornithine as occurs in other spirochetes and bacteria. Intense erythematous reactions were observed after id injection of 10 micrograms of PG into normal human skin. PG was not mitogenic for human peripheral blood mononuclear cells. Murine splenocytes of certain strains responded to the PG, but only at concentrations of 25 micrograms/ml or more. PG stimulated macrophages to produce interleukin 1. Sixteen micrograms of PG injected iv into rabbits produced biphasic fevers. These observations on the in vitro and in vivo activities associated with the cellular components of the B. burgdorferi spirochete give further insight to how a small number of invading organisms can cause a multisystemic disease such as Lyme disease.

Amino Acids↗
PubMed1990

Borrelia burgdorferi in the central nervous system: experimental and clinical evidence for early invasion.

Intravenous injection into adult Lewis rats of live Borrelia burgdorferi, the spirochetal agent of Lyme disease, was followed by increased permeability of the blood-brain barrier. Permeability was measured by the ratio of 125I-labeled albumin in cerebrospinal fluid to that in blood. Permeability changes were dose-dependent, began 12 h after inoculation, and reversed within 1 week. Only live, intravenously inoculated organisms produced impairment of the blood-brain barrier. A spirochetal strain-dependent effect was noted in that changes were more marked with a recent isolate than with a strain in long-term in vitro culture. Mild pleocytosis and spirochetes were noted in the cerebrospinal fluid of rats with increased blood-brain barrier permeability. This experimental evidence for early central nervous system invasion was pursued in studies of the human disease. Specific B. burgdorferi antigens could be detected in the cerebrospinal fluid of patients with early Lyme disease by use of murine monoclonal antibodies as probes.

Animals↗
PubMed1990

Interaction between Borrelia burgdorferi and endothelium in vitro.

During the pathogenesis of Lyme disease, Borrelia burgdorferi spreads hematogenously from the site of a tick bite to several tissues throughout the body. The specific mechanism of spirochete emigration is presently unknown. Using cultured human umbilical vein endothelial cells, we found that Borrelia burgdorferi bound to the endothelial cells and to the subendothelial matrix. Low passage isolates adhered 22-30-fold greater than a strain maintained in culture continuously. Spirochete binding to subendothelial matrix was inhibited 48-63% by pretreatment of the matrix with anti-fibronectin antiserum. Spirochete migration across endothelial monolayers cultured on amniotic membrane was increased when the monolayers were damaged by chemical or physical means. Electron microscopic examination of spirochete-endothelial interactions demonstrated the presence of spirochetes in the intercellular junctions between endothelial cells as well as beneath the monolayers. Scanning electron microscopy identified a mechanism of transendothelial migration whereby spirochetes pass between cells into the amniotic membrane at areas where subendothelium is exposed.

Amnion↗
PubMed1990

Lyme disease in childhood: clinical and epidemiologic features of ninety cases.

In 1982 and 1983 practicing pediatricians in a Lyme disease-endemic county, reported 90 cases of Lyme disease among children 19 years of age and younger (median age, 9 years). Three-fourths of the children had initial symptom onset in the summer months, with peak incidence in July. Infection occurred twice as often in boys than in girls, and tick bites were recalled by less than half (49%) of the children or parents. Erythema chronicum migrans was present in two-thirds (67%) of the cases with median onset 7 days after a definite tick bite. Arthritis or arthralgia occurred in 59% and neurologic symptoms, especially seventh nerve palsy, occurred in 14%. Asymmetric involvement of a few large joints, especially the knee, was most commonly reported for those with joint involvement. antibiotics were prescribed for 79% of the children, three-fourths of whom were treated with oral penicillin. Initial diagnosis of Lyme disease is usually made on clinical grounds alone because serologic tests are often negative. Serologic tests for antibody to Borrelia burgdorferi were more often positive in cases with neurological or joint involvement, in addition to erythema chronicums migrans (80%), than in cases presenting with erythema chronicums migrans only.

Adolescent↗