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J L Benach

Publications and source records attributed to J L Benach.

At least 91 records · Page 5Linked to original sources

Clinical and geographic characteristics of Lyme disease in New York.

The clinical and geographic characteristics of 679 patients who met the clinical definition of Lyme disease and who had antibody titers of greater than or equal to 1: 128 to Borrelia burgdorferi for a two year period, 1983-1984, are described. Males outnumbered females 60% to 40% for the two year period and nearly half of all cases were children and young adults nineteen years old or younger. Forty percent of the patients reported single or multiple tick bites prior to the onset of illness and tick bites were clustered in the summer months. Skin lesions (ECM) were reported in 63% of all the patients. Joint involvement as the only manifestation of Lyme disease was reported in 21% and 22% of all the patients in 1983 and 1984 respectively. A 2: 1 ratio of males to females was noted on this subgroup and 63% of these were 19 years old or less. Onset of joint manifestations were most frequent in the last three months of the year. Neurological manifestations were noted in 20% of the patients with facial palsy being the most frequent. Twenty nine patients had neurological disorders as the only manifestation of Lyme disease. Cardiovascular symptoms were reported in 26 patients (4%). The secondary manifestations of Lyme disease were of summer and early fall onset. Lyme disease in New York is restricted to suburbs north of New York City in Westchester County, and in suburbs to the east of New York City in Suffolk County, Long Island. Incidence for the two year period can range from 0.01 cases per 1000 in some communities to 28 cases per 1000 in highly endemic areas.

Adolescent↗

Lyme disease.

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Arachnid Vectors↗

Isolation of antigenic components from the Lyme disease spirochete: their role in early diagnosis.

Patients with early Lyme disease produce IgM antibodies to a 41,000-dalton polypeptide of Borrelia burgdorferi. With advancing disease, IgG antibodies recognize a larger number of spirochetal polypeptides. Sodium dodecyl sulfate treatment of spirochetes at a concentration of 0.03% resulted in an outer envelope (OE) fraction in the supernatant and a protoplasmic cylinder (PC) flagellar fraction in the pellet. Shearing of the PC pellet followed by ultrafiltration and dialysis resulted in a flagellin-enriched fraction. From the OE and flagellin-rich fractions, individual polypeptides with Mr of 66,000, 41,000, and 31,000/34,000 daltons were eluted in microgram quantities after electrophoresis. The flagellin-enriched fraction as well as the eluted polypeptides were used as antigens in the ELISA. The flagellin-enriched fraction was superior to the standard ELISA antigen. The 41-kilodalton (kDa) flagellin antigen was not useful. Antigens of 66 kDa and 31/34 kDa were confirmed to be part of the late antibody response.

Antibodies, Bacterial↗

Adult Ixodes dammini on rabbits: a hypothesis for the development and transmission of Borrelia burgdorferi.

A histological study of unfed Ixodes dammini adults has shown that the Lyme disease spirochete can be found in the midgut diverticula of these ticks and is presumably carried over from the nymphal stage. Sequential histology of the early stages of ticks feeding on a rabbit showed that spirochetes began to divide and were located in close proximity or attached to the epithelial cells of the diverticulae. Evidence for division was obtained by the higher number of spirochetes per tick after a three-day feeding period than in the unfed females. Although the mechanism is unclear, some spirochetes become systemic by the fifth day of feeding and can be detected in low numbers in other tick organs. Spirochetes were also noted in the feeding cavities created by I. dammini in the dermis after five days of attachment. Spirochetes were not detected in salivary glands or in the feces of I. dammini during the feeding period.

Animals↗

Lyme disease during pregnancy.

Lyme disease is an increasingly recognized tick-borne illness caused by a spirochete, Borrelia burgdorferi. Because the etiologic agent of Lyme disease is a spirochete, there has been concern about the effect of maternal Lyme disease on pregnancy outcome. We reviewed cases of Lyme disease in pregnant women who were identified before knowledge of the pregnancy outcomes. Nineteen cases were identified with onset between 1976 and 1984. Eight of the women were affected during the first trimester, seven during the second trimester, and two during the third trimester; in two, the trimester of onset was unknown. Thirteen received appropriate antibiotic therapy for Lyme disease. Of the 19 pregnancies, five had adverse outcomes, including syndactyly, cortical blindness, intrauterine fetal death, prematurity, and rash in the newborn. Adverse outcomes occurred in cases with infection during each of the trimesters. Although B burgdorferi could not be implicated directly in any of the adverse outcomes, the frequency of such outcomes warrants further surveillance and studies of pregnant women with Lyme disease.

Adult↗

Interleukin 1: a common endogenous mediator of inflammation and the local Shwartzman reaction.

In this study we investigated the role of interleukin 1 (IL 1) in the induction of inflammatory lesions and in the preparation and provocation of the local Shwartzman reaction. Both of these phenomena can be induced with a variety of agents. This suggested to us that a common endogenous mediator may be crucial to the development of these two lesions. When IL 1 was injected intradermally into shaved rabbit backs, 51Cr-labeled neutrophils accumulated at the injection site. Neutrophils began to accumulate less than 1 hr after injection, and the maximum rate of accumulation was observed by 4 hr. This activity was dose dependent. It was calculated that in all animals, 10(-14) mol of IL 1 induced significant neutrophil accumulation, whereas in many animals, as little as 10(-15) mol of IL 1 sufficed. When 4.2 X 10(-9) mol of E. coli 0111:B4 lipopolysaccharide W was injected i.v. 24 hr after an intradermal injection of IL 1 (2.9 X 10(-13) mol), a local Shwartzman reaction was seen 4 hr later at the intradermal injection site. IL 1 injected i.v. 24 hr after an intradermal injection of either IL 1 or lipopolysaccharide also produced a local Shwartzman reaction. These data indicate that IL 1 may be the common endogenous mediator of the inflammatory response, and IL 1 may serve in the same role for the preparation and provocation of the local Shwartzman reaction.

Animals↗

Childhood Lyme arthritis: experience in an endemic area.

We report 25 children with oligoarticular arthritis associated with Lyme disease. There were 16 boys (male/female ratio 1.8:1); ages ranged from 2 to 15 years. Thirteen (52%) children had no history of erythema chronicum migrans or other rash. Thirteen had temperatures as high as 41 degrees C for up to 2 months before the onset of arthritis. Twelve recalled definite tick bites. Ten (40%) children, of whom seven had no history of rash, were hospitalized for presumed septic arthritis. Another four had diagnoses of pauciarticular juvenile rheumatoid arthritis for as long as 3 years. Seven patients had less acute, recurrent episodes of synovitis. Two children had seventh nerve palsies 2 months before onset of arthritis. All patients had antibodies to the Lyme spirochete. In 14 patients, synovial fluid white blood cell counts ranged from 180 to 97,700/mm3 (greater than or equal to 76% polymorphonuclear leukocytes). Antibiotic therapy was effective in all patients; in 13, orally administered therapy alone resulted in elimination of synovitis and recurrent attacks. Lyme arthritis may be confused with acute bacterial septic arthritis or recurrent "pauciarticular juvenile rheumatoid arthritis," particularly when there is no history of erythema chronicum migrans.

Adolescent↗

Isolation of the outer envelope from Borrelia burgdorferi.

Borrelia burgdorferi consists of an inner protoplasmic cylinder, containing the genome and cytoplasmic elements, surrounded by a number of axial filaments, all completely encased within a multiple-layered outer envelope structure (OE). In this study, a sodium dodecyl sulfate-mediated technique was used to isolate the OE from Borrelia burgdorferi in an attempt to better understand this structure in terms of its antigenic reactivity to Lyme disease patient sera. Electron microscopic evidence suggested that the OE product was relatively free of other spirochete cellular components. SDS-PAGE analysis indicated that the electrophoretic pattern of the OE was consistent with that of the remaining protoplasmic cylinder (PC) and whole spirochete controls. Antigenic determinants in the OE were recognized by sera from Lyme disease patients in Western blots. Chemical analysis of the OE revealed a composition of 45.90% protein, 50.75% lipid and 3.33% carbohydrate. The OE comprised 16.5% by lyophilized dry weight of the whole spirochete. Antigenic determinants located within or associated with this structure are likely to play a significant role in the development of immunity in the infected host.

Antigens, Bacterial↗

An IgE response to spirochete antigen in patients with Lyme disease.

Most but not all Lyme disease patients produce specific IgE antibodies to Borrelia burgdorferi. Development of IgE antibodies paralleled that of other immunologic classes and appeared to be directed against a polypeptide with a molecular weight of 41,000. Total serum IgE levels in Lyme disease patients were usually within the normal range in all stages of the disease. However, highly elevated total serum IgE in certain patients were not correlated to any particular disease stage nor to specific antibody titers. Spirochetes and spirochetal sonicates in high concentration induced release of histamine from basophils derived from both patients and controls. At lower antigen concentrations, histamine release could be induced only from basophils derived from patients. Synovial fluids from patients with Lyme arthritis contained IgE but only negligible amounts of histamine.

Antigens, Bacterial↗

A role for interleukin-1 in the pathogenesis of Lyme disease.

Interleukin-1 (IL-1) is the major immunoregulatory molecule produced by macrophages in response to a variety of environmental insults including chemicals, phagocytosis, bacteria, and bacterial products. Macrophages stimulated by Borrelia burgdorferi produced large quantities of IL-1 when spirochetes were added to macrophages at a ratio of 10 spirochetes per macrophage. The release of IL-1 was dose dependent: a single spirochete per macrophage was sufficient to produce significant quantities of IL-1. Spirochetal lipopolysaccharide was not required for this activity in that polymyxin B in the spirochete-macrophage culture had no effect on IL-1 production. Normal murine fibroblasts cultured with this IL-1 were shown to have an increased rate of DNA synthesis and an increase in secreted collagenase. IL-1 was found in joint fluids from Lyme disease patients. When IL-1 was injected intradermally into the backs of rabbits, the injection sites became indurated, erythematous, and warm to the touch after 4 hrs and annular lesions much like those of erythema chronicum migrans were seen in some animals after 24 hrs. B. burgdorferi is a powerful inducer for IL-1 in vitro, and it is reasonable to presume that it acts similarly in Lyme disease patients. Our results suggest that IL-1 in turn, may play a role in many of the clinical manifestations of Lyme disease.

Animals↗

Borrelia burgdorferi lipopolysaccharide and its role in the pathogenesis of Lyme disease.

Lipopolysaccharides (LPS) are a constitutive part of the outer wall of gram negative bacteria. Because many of the symptoms of Lyme disease could be explained by a spirochetal LPS we have subjected Borrelia burgdorferi to standard LPS extraction techniques which yielded a LPS which accounted for 1.5-4% of the dry weight. The LPS was very similar to classical gram negative bacterial LPS both chemically and in its biological activities which included pyrogenicity, mitogenicity for lymphocytes and the induction of Interleukin 1 production by macrophages. In addition, the LPS produced an acute inflammatory reaction when injected intradermally into rabbit skin. It could also prepare a skin site for the production of the local Shwartzman reaction. These results show that the Lyme disease spirochete contains a hitherto unknown LPS that is biologically active in vitro and in vivo. It is likely that this molecule plays an important role in the pathogenesis of Lyme disease.

Animals↗

Cellular immune response in Lyme disease: the response to mitogens, live Borrelia burgdorferi, NK cell function and lymphocyte subsets.

Although some manifestations of Lyme disease may be secondary to the presence of B. burgdorferi, the immune system appears to play a significant role in the clinical manifestations of the disease. The humoral response is well characterized, however the cellular response remains poorly defined. To further define cellular immunity in Lyme disease, the responses of lymphocytes from patients with active Lyme disease were assessed to Con a, PHA, PWM, tetanus toxoid, and whole live B. burgdorferi. In addition, the natural killer cell (NK) function of these patients was assayed. As compared to the controls the lymphocyte response to Con A was reduced and the response to PHA was increased. There was a significant proliferative response to B. burgdorferi in all patients with no response in the controls. The responses to PWM and tetanus toxoid were not different in the two groups. NK cell function in the patients with active disease was reduced as compared to the normal controls and patient's who were not clinically active. We conclude that there is a significant alteration in cellular immunity in active LD consistent with a defect in the induction of suppressor cells leading to a vigorous humoral response.

Antibodies, Monoclonal↗

Chemical and biologic characterization of a lipopolysaccharide extracted from the Lyme disease spirochete (Borrelia burgdorferi).

A lipopolysaccharide (LPS) was isolated from the Lyme disease spirochete by a modification of the hot phenol-water method. The material was composed of 45% carbohydrate, 8% protein, 44% lipid A, and 1% 3-deoxy-D-mannooctulosonic acid and accounted for approximately 1.5% of the cellular dry weight. The isolated LPS possessed several biologic activities characteristic of endotoxins. The LPS was pyrogenic for rabbits, mitogenic for human mononuclear cells and murine splenocytes, capable of clotting limulus lysate, and cytotoxic for murine macrophages. LPS extracted from Borrelia burgdorferi by the petroleum-ether:chloroform:liquid-phenol procedure was also characterized. The results show that the Lyme disease spirochete contains a hitherto unknown LPS that is biologically active in vitro, and the expression of such activities in vivo may play an important role in the pathogenesis of Lyme disease. Some of the clinical manifestations of other spirochetal disease may be explained by similar endotoxins in those organisms. To our knowledge this is the first report of an LPS extracted from a spirochete that is known to be a human pathogen.

Animals↗

Serological evidence for simultaneous occurrences of Lyme disease and babesiosis.

Babesia microti and Borrelia burgdorferi, the spirochetal agent of Lyme disease, are both transmitted by the tick Ixodes dammini. Serological evidence has shown that 54% of the patients with babesiosis tested have IgG and IgM antibodies to the spirochete causing Lyme disease. Likewise, 66% of randomly selected patients with Lyme disease from geographic areas endemic for both diseases, but not from areas where babesiosis does not occur, also have IgM and IgG antibodies to B. microti. Antigenic cross-reactivity is not the reason for these findings, as laboratory animals experimentally infected with B. microti do not develop antibodies to B. burgdorferi, and laboratory animals immunized with organisms derived from pure cultures of spirochetes do not develop antibodies to B. microti. We suggest that these patients are concurrently exposed to both organisms by doubly infected tick vectors.

Animals↗

Lyme disease spirochetes induce human and murine interleukin 1 production.

IL 1 is a major immunoregulatory molecule produced by macrophages, and it appears to be the molecular orchestrator of nonspecific host defense mechanisms against a variety of environmental insults. Many investigators have used artificial agents to stimulate macrophages to produce IL 1. We now report production of large quantities of IL 1 after a physiologic stimulus. The Lyme disease spirochete, recently isolated and adapted for growth in vitro, was used to stimulate P388D1 cells or human peripheral blood monocytes. Spirochetes were added to confluent macrophage cultures in serum-free RPMI at a ratio of 10:1. The release of IL 1 was dose-dependent. The 24-hr supernatant IL 1 activity was determined by using the thymocyte Con A co-mitogenesis assay. Activity was not due to an endotoxin on, or produced by, the spirochete. A polymyxin B affinity column failed to remove activity, and polymyxin B in the spirochete-macrophage culture had no effect on IL 1 production. Supernatants were collected, were concentrated, and were subjected to size exclusion HPLC. Three areas of activity were found in P388D1 cell supernatants (Mr greater than 60,000, 40,000, and 20,000), whereas two peaks (Mr 23,000 and 13,000) were found in human monocyte supernatants. The Mr 20,000 and 13,000 peaks from murine and human cell supernatants, respectively, were subjected to SDS-PAGE and were shown to be single bands (Mr 12,400 for the mouse IL 1 and Mr 13,500 for the human IL 1). Isoelectric focusing of column-purified IL 1 preparations showed two different pI in both human (pI 7.25 and 4.4 to 5) and murine (pI 7.25 and 5.55) IL 1. Fibroblasts cultured with murine or human IL 1 preparations demonstrated both an increase in secreted collagenase and increased cell proliferation. Thus, a physiologic stimulus and simple biochemical techniques produce large amounts of very pure mouse or human IL 1. That this IL 1 is produced by Lyme disease spirochete-stimulated macrophages may explain some of the clinical manifestations of Lyme disease.

Animals↗

Babesiosis in splenectomized adults. Review of 22 reported cases.

Since 1957, there have been 22 reported cases of human babesiosis in splenectomized persons, representing about one third of all clinical human babesiosis. Splenectomy had been performed one month to 36 years (mean 8.7 years, median 6.0 years) earlier for a variety of reasons. Four of the seven European cases were from Babesia divergens whereas 12 of the 15 United States cases were from B. microti. Most of the 22 patients had moderate to severe clinical disease including hemolytic anemia, yet all but six recovered. Three patients had transfusion-acquired babesiosis. Treatments employed included the use of chloroquine, quinine, pyrimethamine, pentamidine, clindamycin, dialysis, and exchange transfusion. Splenectomized and/or otherwise immunocompromised hosts should be advised to avoid visiting endemic areas for babesiosis such as Nantucket Island or Martha's Vineyard in Massachusetts and Shelter Island and other parts of Long Island, New York. Babesiosis must be considered as one of the not uncommon organisms responsible for the postsplenectomy sepsis syndrome and one for which there is no current prophylaxis.

Adult↗