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S A Larsen

Publications and source records attributed to S A Larsen.

At least 19 recordsLinked to original sources

Anatomical evidence of synaptic plasticity in the cochlear nuclei of white-deaf cats.

Synapses are dynamic structures reflecting environmental events. It was observed that densities associated with apposing synaptic membranes were altered in response to changing conditions of auditory stimulation (Gulley et al. 1978. J. Comp. Neurol. 180: 707-742). Synapses also exhibit plasticity during early development of the auditory system (Larsen and Pappas, 1985. Proceedings: 43rd Annual Meeting of the Electron Microscopy Society of America, pp. 493-494). Larsen and Pappas reported that, in young kittens, the end bulb of Held (EBH) terminal was distinguished by excessive density at apposing synaptic membranes which assume gradually the pattern observed in adult cats. The maturation of synapses parallels emerging function and may depend upon auditory stimulation (Larsen and Kirchhoff, 1987. Neurosci. Abstr. 13: 1260). Larsen and Kirchhoff found that EBH synapses on large spherical cells of white-deaf cats resembled the immature synapses found in young kittens (Fig. 1). They also found terminals that had an increased number and length of the membrane densities associated with synapses. Because the number of synaptic vesicles in these presynaptic terminals was equivalent to the number of vesicles found in normal-hearing cats, Larsen and Kirchhoff (1987) suggest that this is evidence of synaptic plasticity. We have completed a quantitative study of the synapses of EBH terminals found in adult cats that had been deaf for at least 3 years.

Albinism

Seroepidemiological characterization of a syphilis epidemic in the Republic of the Marshall Islands, formerly a yaws endemic area.

The annual numbers of reported cases of syphilis in the Republic of the Marshall Islands (RMI) increased from none in 1983 to more than 600 in 1989, suggesting a large outbreak of syphilis. Much of the increase resulted from expanded serological screening. The apparent outbreak of syphilis, therefore, may have been partly the result of increased surveillance or, since the RMI was formerly a yaws endemic area, possibly due to a resurgence of yaws. To address this problem and better characterize the epidemic, we analysed results from a 1989/90 Ministry of Health Services mass serological screening on Majuro Atoll, the main population centre. Serum specimens from 9160 people (86% of residents aged 15-44 years) on Majuro were screened with the rapid plasma reagin (RPR) card test; we repeated the RPR and performed a confirmatory microhaemagglutination assay for Treponema pallidum-specific antibodies (MHA-TP) on a sample of serum specimens. To estimate the seroprevalence of syphilis, we also tested a sample of RPR nonreactive specimens by MHA-TP. Among people less than 45 years of age, total (11.5%) and high-titre (5.2%) seropositivity rates were highest in the 20-24 year age group, as was MHA-TP seroprevalence (15.9%). These results suggested that a large outbreak of syphilis was responsible for the observed seroreactivity. Cumulative incidence modelling and comparisons with the results of a previous serosurvey conducted in 1985 suggested that the duration of the syphilis epidemic was approximately 10 years and that incidence had not increased appreciably since 1985.

Adolescent

Specific immunofluorescent staining of pathogenic treponemes with a monoclonal antibody.

Two hybrid cell lines which produced mouse monoclonal antibody to the DAL-1 street strain of Treponema pallidum subsp. pallidum were established. These monoclonal antibodies strongly reacted with T. pallidum subsp. pallidum (Nichols strain, DAL-1, and two other street strains, strains MN-1 and MN-3) and T. pallidum subsp. pertenue by indirect microimmunofluorescent antibody and enzyme-linked immunosorbent assay techniques, but they did not react with normal rabbit testicular tissue. These monoclonal antibodies did not react with nonpathogenic treponemes, such as T. phagedenis Reiter, T. denticola MRB, T. refringens Noguchi, or other spirochetes, such as Borrelia burgdorferi and Leptospira interrogans serovar pomona in microimmunofluorescent antibody smear slides or in Western blots (immunoblots). While unlabeled antibodies are useful for investigating the antigenic structures of T. pallidum, we labeled these monoclonal antibodies with fluorescein isothiocyanate and used them for diagnosing syphilis by direct staining of lesion exudate or T. pallidum subsp. pallidum in formalin-fixed tissues from patients suspected of having syphilis. Both monoclonal antibodies were directed against antigens of T. pallidum subsp. pallidum with a molecular weight of 37,000 as determined by the Western blotting technique.

Animals

Specific immunofluorescence staining of Treponema pallidum in smears and tissues.

To date, tissue sections prepared from Formalin-fixed tissues have not been successfully stained with Treponema pallidum subspecies-specific antibody in a direct fluorescent-antibody assay. While current methods stain T. pallidum, they do not distinguish T. pallidum from other spirochetes such as Borrelia burgdorferi (E. F. Hunter, P. W. Greer, B. L. Swisher, A. R. Simons, C. E. Farshy, J. A. Crawford, and K. R. Sulzer, Arch. Pathol. Lab. Med. 108:878-880, 1984). Because trypsin pretreatment of tissue sections has enhanced other immunofluorescent-antibody (IFA) applications, we compared the use of the trypsin digestion method with the current 1% ammonium hydroxide (NH4OH) method as a means to obtain specific staining of T. pallidum in tissues by both direct and indirect IFA techniques. Pretreated T. pallidum-infected tissues sections from rabbits, hamsters, and humans were quantitatively examined with the direct fluorescent-antibody-T. pallidum test conjugate absorbed with Treponema phagedenis, the Reiter treponeme. For indirect staining, a serum specimen from a patients with syphilis absorbed by affinity chromatography with T. phagedenis was used as the primary reagent, and a fluorescein isothiocyanate-labeled rabbit anti-human globulin was used as the secondary reagent. Serum specificity was established first by examining antigen smears of T. pallidum subsp. pallidum, T. pallidum subsp. pertenue, B. burgdorferi, T. phagedenis, and Treponema denticola MRB and then by examining tissues infected with these pathogens plus those infected with four Leptospira serovars. When we stained tissue using the direct IFA method that is currently a standard method for the examination of chancre smears, we found it to be unsuitable for use with tissue. Trypsin digestion did not offer an improvement over the NH4OH pretreatment method in the specific identification of T. pallidum by direct IFA. However, specific identification of T. pallidum in tissue sections was obtained by the indirect IFA technique after either trypsin or NH4OH pretreatment.

Animals

Sensitivity of treponemal tests for detecting prior treated syphilis during human immunodeficiency virus infection.

To evaluate the sensitivity of treponemal tests as a marker of prior syphilis in individuals with human immunodeficiency virus (HIV) infection, the syphilis serology of 109 homosexual men with a documented history of treated syphilis was compared with records of prior results and confirmed on stored serum samples. None of the HIV-seronegative individuals lost reactivity to a treponemal test, whereas 7% of the seropositive asymptomatic individuals and 38% of those with symptomatic HIV infection had loss of reactivity. Symptomatic HIV infection was associated with loss of reactivity, as a T4 lymphocyte count less than 200 X 10(6)/1, a T4-to-T8 ratio less than 0.6, a single prior episode of syphilis, and a low VDRL titer at the time of the last documented episode of syphilis. Although no conclusions can be drawn about the sensitivity of treponemal tests in patients with active syphilis and HIV infection, these data suggest that treponemal tests may not identify those previously infected with Treponema pallidum.

Adult

Race and the prevalence of syphilis seroreactivity in the United States population: a national sero-epidemiologic study.

We used the 1978 National Health and Nutrition Examination Survey to examine the prevalence of positive syphilis serologies in the US population. Analysis of risk markers--gender, age, marital status, education, income, and residence--indicates that all except gender are associated with syphilis seroreactivity, independent of race. Controlling for associated risk markers, the Black-White odds ratio of syphilis seroreactivity is 4.7 (95% CI = 2.7, 8.2). Current knowledge of racial differences in sexual and health care behavior does not explain the Black-White difference in the prevalence of syphilis seroreactivity.

Adolescent

Syphilis.

The clinical manifestations of syphilis can resemble many diseases. The diagnosis can be confirmed through serologic tests and by direct microscopic observation of Treponema pallidum, subspecies pallidum in lesion, biopsy, or autopsy specimens. Direct microscopic examination may be carried out by darkfield methods or by immunofluorescent staining. The serologic testing sequence is usually a screening nontreponemal test followed by confirmation with a specific treponemal test. Serologic tests for syphilis have been highly standardized in the past, but today quality control lies in the hands of the laboratorian.

Humans

Detection of immunoglobulin M in cerebrospinal fluid from syphilis patients by enzyme-linked immunosorbent assay.

Cerebrospinal fluid (CSF) samples were evaluated in an immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) for syphilis with sonic extracts of Treponema pallidum coated on polystyrene plates. The ELISA procedure was reproducible, and T. pallidum antigens were stable., A total of 15 CSF samples from patients with neurosyphilis, 18 CSF samples from patients with syphilis, 12 CSF samples from patients treated for syphilis, and 494 CSF samples from patients with neurologic or other systemic diseases were tested. The IgM ELISA gave reactive results in all of six symptomatic and congenital neurosyphilitic patients and none of nine asymptomatic neurosyphilitic patients. Of 524 CSF samples from nonneurosyphilitic individuals, 513 were nonreactive, resulting in 98% test specificity. The IgM ELISA in CSF should prove to be useful for confirmation of symptomatic neurosyphilis.

Albumins

Serological response to syphilis treatment. A new analysis of old data.

One important aspect of the posttreatment evaluation of patients with early syphilis is assessment of serological test results. Using information previously collected from 818 patients in the Early Syphilis Study, we evaluated the seroresponse of people treated for primary or secondary syphilis. We generated curves describing the VDRL titer declines with time. The VDRL titer declined approximately fourfold at three months and eightfold at six months. These observations will allow clinicians to identify treatment failures or reinfections at the earliest possible time during their follow-up.

Antibodies, Bacterial

Adenovirus ELISA for the evaluation of cerebrospinal fluid in patients with suspected neurosyphilis.

An enzyme-linked immunosorbent assay (ELISA) detecting antibodies against the adenovirus group antigen was used to examine cerebrospinal fluid (CSF) of suspected neurosyphilis patients for serum contamination or blood-brain barrier (BBB) leakage. Adenovirus antibodies are ubiquitous, produce high antibody titers, and rarely cause central nervous system (CNS) infections. Of 52 normal adult sera tested with this ELISA, only one lacked antibodies. CSF from 48 healthy individuals did not present a detectable amount of anti-adenovirus antibodies. CSF from 33 suspected neurosyphilis patients with positive results in the fluorescent treponemal antibody-absorption (FTA-ABS)-CSF test were examined. Eighteen showed anti-adenovirus antibodies indicating contamination of the CSF with peripheral blood or damaged BBB by syphilis or other disease, resulting in questionable CSF treponemal results. The remaining 15 of these patients appeared to be producing their anti-treponemal antibodies in the CNS. This procedure may prove to be of considerable help in excluding false positive FTA-ABS results in CSF samples.

Adenoviridae

Four-step enzyme-linked immunosorbent assay for detection of Treponema pallidum antibody.

Further studies of a four-step enzyme-linked immunosorbent assay procedure to detect Treponema pallidum antibody are described. High-titered antibody, produced in rabbits by intravenous injection of T. pallidum, was used to coat polyvinyl chloride microtiter plates. To these plates a known concentration of T. pallidum was added, followed in successive steps by serial dilutions of human sera and appropriately diluted peroxidase-labeled anti-human immunoglobulin G antibody. O-Phenylenediamine was the substrate. A total of 340 sera were obtained from the DeKalb County Sexually Transmitted Diseases Clinic, Atlanta, Ga., and examined within 3 days of receipt. Ninety-six percent test agreement between the enzyme-linked immunosorbent assay and the fluorescent treponemal antibody absorption-double staining test was obtained. A total of 372 additional sera stored at -20 degrees C were examined. The overall sensitivity of the enzyme-linked immunosorbent assay with sera from patients with various stages of syphilis was 96%. With sera from uninfected individuals, the specificity of the enzyme-linked immunosorbent assay was 95%. No antigen instability was noted with the two antigen preparations used during this evaluation.

Antibodies, Bacterial

Rheumatoid factor in syphilis.

Immunoglobulin M (IgM) antibodies directed against IgG antibodies (rheumatoid factor [RF]) are known to occur often in patients with syphilis and to interfere with serological tests measuring specific antibodies of the IgM class. In this study we examined the occurrence and specificity of the RF and demonstrated a simple method to detect and eliminate the RF for a specific Treponema pallidum IgM enzyme-linked immunosorbent assay. We measured the occurrence of the RF with a sensitive enzyme-linked immunosorbent assay and found that it increased with the duration of syphilitic disease: 1 of 13 primary syphilis serum specimens, 3 of 13 secondary syphilis serum specimens, and 10 of 27 latent syphilis serum specimens were reactive in this RF test. Those sera containing IgM RF were immunoprecipitated with anti-human gamma chain antibodies and 2% polyethylene glycol until the RF was removed. One serum specimen from a patient in the secondary stage of syphilis and eight serum specimens from patients with latent disease still presented the RF after immunoprecipitation. Removal of the IgG antibodies also improved the sensitivity of the treponemal IgM test, indicating competition of these antibodies for binding sites of the antigen. The enzyme-linked immunosorbent assays for detection of RF and antitreponemal IgM antibodies are performed on the same plate. Theoretically, only sera positive for both tests have to be immunoprecipitated. But our findings indicated an increase in sensitivity of the IgM enzyme-linked immunosorbent assay after removal of IgG antibodies responsible for competition at the binding sites.

Antibodies, Anti-Idiotypic

Epidemiological characterization of Neisseria gonorrhoeae by lectins.

A total of 101 isolates of penicillinase-producing and non-penicillinase-producing Neisseria gonorrhoeae with known nutritional requirements, plasmid content, and serovars, were examined for lectin agglutination patterns. These isolates were from outbreaks in Georgia, California, Hawaii, and Pennsylvania. Cell suspensions made from 16- to 18-h cultures were mixed with 14 different lectins, and the resultant agglutination patterns were classified as agglutination groups. Among the 101 isolates tested, 24 different agglutination groups were demonstrated. Of the organisms tested, 55% were located in 3 of the 24 groups, and 86% of the isolates reacted with the lectins Trichosanthes kinlowii, Griffonia simplicifolia I, peanut agglutinin, soybean agglutinin, potato agglutinin, and wheat germ agglutinin. One isolate did not react with peanut or potato agglutinin, five isolates lacked reactivity with potato agglutinin, and six isolates did not react with wheat germ agglutinin. Of the wheat germ-negative isolates, four were from Pennsylvania and were identical with regard to auxotype, plasmid content, serovar, and lectin group. The other two wheat germ-negative isolates were from California and were unrelated by the same criteria to the four Pennsylvania isolates and to each other. Among the isolates tested, there were no differences in lectin groups with regard to the sex of the patient. In the Georgia collection, agglutination with one lectin group was confined to isolates of serogroup IA. This association was not observed for the other geographic areas. Some isolates showing identical auxotype, plasmid content, and serovars could be differentiated based on lectin agglutination patterns, whereas other isolates were identical by all testing criteria.

Agglutination Tests

Lectin characterization of gonococci from an outbreak caused by penicillin-resistant Neisseria gonorrhoeae.

A total of 40 Neisseria gonorrhoeae isolates, representing 19 penicillin-resistant isolates (from 8 heterosexual patients and 11 homosexual patients) and 21 penicillin-susceptible isolates (from 15 heterosexual patients and 6 homosexual patients) and obtained from the same geographic area, were examined. Lectin agglutination patterns were based on the reactivity of the isolates with the following 14 lectins: concanavalin A, Lens culinaris, Trichosanthes kinlowii, Griffonia simplicifolia I, Arachis hypogeae (peanut agglutinin), Glycine max (soybean agglutinin), Dolichos bifloris, Griffonia simplicifolia II, Solanum tuberosum (potato starch agglutinin), Triticum vulgaris (wheat germ agglutinin), Limax flavus, Phaseolus vulgaris, Ulex europaeus I, and Lotus tetragonolobus. All isolates were serotyped with monoclonal antibodies specific for gonococcal outer membrane protein I and auxotyped, and the plasmid content was determined. Resistant patient isolates were selected for their decreased penicillin susceptibility, and control isolates were selected for their penicillin susceptibility. Even though the patient isolates demonstrated resistance to penicillin, no phenotypic differences in lectin-grouping patterns were demonstrated between the two study groups; i.e., two predominant lectin groups were observed. No resistance-associated plasmids were detected. All patient isolates were serogroup IB (serovars IB-1, IB-2, and IB-4), whereas 12 of 21 control isolates were serogroup IA (P less than 0.05). Isolates obtained from different anatomical sites in the same patient (cervical and rectal) agreed with regard to lectin patterns and serovars but not auxotypes.

Agglutination Tests

Problems affecting performance of the fluorescent treponemal antibody-absorption test for syphilis.

Immunofluorescent staining of Treponema pallidum was studied to clarify the effect of three factors on the results of the fluorescent treponemal antibody-absorption test: (i) heat inactivation of sera at 56 degrees C for 30 min before testing, (ii) use of multicircle slides, and (iii) tungsten illumination to visualize and assess unstained treponemes on reactive as well as nonreactive smears. It was found that serum inactivation before testing was not necessary for detection of immunoglobin G antibody, but an immunoglobulin M prozone was detected in unheated serum. On multicircle slides, it was demonstrated that a false-positive reaction could be obtained in 30 s at 37 and 25 degrees C if a smear where a nonreactive serum had been placed was crossed by a strongly reactive serum from another circle. Tungsten illumination proved necessary for correct assessment of unstained treponemes on all fluorescent treponemal antibody-aborption test smears, reactive or nonreactive. The possible role of these factors in incorrect fluorescent treponemal antibody-absorption test results is discussed.

Antibodies, Bacterial