Biomedical subjects

G Leonard

Publications and source records attributed to G Leonard.

At least 37 records · Page 2Linked to original sources

PubMed1997

Interferon gamma expression in human nasal polyps.

One feature among nasal polyps (NPs) is the predominance of lymphocytes and eosinophils. We hypothesize that elevated levels of interferon gamma (IFN-gamma) activate lymphocytes and eosinophils within the NP microenvironment. Nasal polyps were evaluated for distribution and levels of IFN-gamma in specimens from 27 patients with nasal polyposis and 4 controls. Immunohistochemical study revealed IFN-gamma staining of eosinophils, glandular cells, and epithelium (27 of 27 patients). ELISA analysis indicated elevated IFN-gamma levels in total NP tissues (25.6 +/- 7.23 pg/mg total protein [TP]) compared with controls (16.27 +/- 6.54 pg/mg TP). Three subpopulations were identified based on IFN-gamma levels: low IFN-gamma group (10.7 +/- 5.51 pg/mg TP); medium IFN-gamma group (25.70 +/- 5.90 pg/mg TP); and high IFN-gamma group (52.58 +/- 10.29 pg/mg TP). The latter levels were approximately 3.5 times the control levels (P<0.0025). Patients with previous polypectomy surgery showed higher levels of IFN-gamma compared with controls (P<0.0423). A trend was found with increased IFN-gamma levels and allergy, asthma, and topical steroid use.

Adult↗

PubMed1997

Murine model of interleukin-8-induced otitis media.

Interleukin-8 (IL-8), a potent inflammatory mediator that is thought to control leukocyte recruitment and activation during inflammatory reactions, has been implicated in a variety of inflammatory diseases. Recent studies in our laboratory have demonstrated the presence of IL-8 in chronically inflamed human middle ear effusions. These data have led us to hypothesize that IL-8 is responsible for the leukocyte recruitment seen in otitis media. Because the effect of IL-8 on the middle ear mucosa has not been investigated and therefore its role in middle ear inflammation is not known, we investigated the ability of IL-8 to directly induce inflammation in the murine middle ear. For these studies, ICR mice were used to test the hypothesis that IL-8 could directly induce inflammation in the middle ear. Murine middle ears received 8-mL transtympanic injections of human IL-8 (25 mg/mL) in saline, heat-killed Streptococcus pneumoniae (1 x 10(8)/mL), or normal saline. Temporal bones were removed at 1, 4, 8, 24, and 48 hours, decalcified, and processed for histologic examination. Noninjected murine temporal bones served as controls. Normal saline-injected ears demonstrated little to no change as compared with temporal bones from noninjected ears. IL-8-injected ears histologically demonstrated thickening of the epithelial layer and subepithelial space (SES), with inflammatory cell infiltration in the SES peaking at 4 to 8 hours and resolving by 48 hours. Bacteria-injected ears demonstrated findings similar to, although not as extensive as, those found in IL-8-injected ears (i.e., inflammatory reactions peaked at 8 to 24 hours and resolved by 72 hours). Our results demonstrate that IL-8 is a potent inducer of middle ear inflammation and support the concept that IL-8 may be one of the key cytokines responsible for the leukocyte accumulation and activation seen in otitis media.

Animals↗

PubMed1995

Visual-spatial localization by patients with frontal-lobe lesions invading or sparing area 46.

Monkeys with unilateral principal sulcus (PS) lesions show a contralateral deficit in localizing remembered targets, especially as the recall interval is lengthened. We tested 20 patients with unilateral frontal-lobe excisions that invaded (FI) or spared (FS) area 46 (putative homologue of PS) and 32 normal controls (NC) on a task where subjects had to indicate the location of a light dot either immediately, or after 30 s, with or without interference. The FI group was worse than the NC group following both delay conditions. NC and FS groups differed only after interference. We concluded that area 46 is involved in recalling the location of visual targets, but unlike the monkey, the deficit is not restricted to a particular part of the visual field.

Adult↗

PubMed1995

The effects of frontal- or temporal-lobe lesions on susceptibility to interference in spatial memory.

Patients with unilateral frontal- or temporal-lobe lesions and normal control subjects studied multiple arrays of pictures and were tested for recall of the locations of the pictures. One condition consisted of three trials of the same pictures in different spatial arrangements, recall being tested immediately after each presentation. In a second condition (using different stimuli), the subject was given two trials with one set of pictures, but a new set of pictures was viewed on the third trial. All groups showed a build-up of proactive interference across trials using the same pictures, and a release of proactive interference when they studied new pictures. Patients with frontal-lobe lesions were more susceptible to proactive interference than were the other groups.

Adolescent↗

PubMed1995

Recall of self-generated arm movements by patients with unilateral cortical excisions.

In previous work, Leonard and Milner (Neuropsychologia, 29, 47-58, 1991) demonstrated that patients with large excisions from the right frontal lobe have difficulty in reproducing accurately the extent of examiner-defined arm movements, the displacements being made without the aid of vision. The impairment in the right frontal-lobe group was not dependent on recall-condition, being apparent irrespective of the presence of a delay, suggesting that the deficit was primarily one of encoding. We then went on to show that these same patients have a short-term memory deficit when recalling terminal position of examiner-defined arm movements (Neuropsychologia 29, 629-640, 1991). From these investigations we concluded that the right frontal lobe is critically involved in the monitoring of information related to movement. In the present study 58 patients with unilateral temporal- or frontal-lobe excisions were tested on two kinesthetic tasks that required the subjects themselves to select terminal positions, or movement extents, thereby reducing dependence on peripheral feedback. Patients with right frontal-lobe lesions could reproduce these self-generated movements normally, indicating that when demands on feedback are reduced the frontal-lobe contribution is not critical.

Adolescent↗

PubMed1994

Dyadic affect regulation in three caregiving environments.

Investigation of patterns of mother-child affect across three caregiving groups indicated that both adolescent and adult high-social-risk mothers showed less individual positive affect than did adult low-social-risk mothers. High-social-risk adolescent mothers also showed more individual negative affect and participated with their children in more dyadically misregulated affect exchanges than did adult mothers from either high- or low-social-risk environments.

Adaptation, Psychological↗

PubMed1994

Cytokines in experimental otitis media with effusion.

Studies in the authors' laboratory have recently demonstrated the presence of potent inflammatory cytokines such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) in human middle ear effusions. The clinical significance of this finding has not been fully elucidated because of the limitations of human studies. We hypothesized that the chinchilla model of otitis media may be an appropriate system with which to study the role of cytokines in otitis media with effusion. To begin to investigate this possibility, 30 chinchillas underwent surgical blockage of the eustachian tube (ET) to promote effusion development. After 2 weeks, examination by otoscopy demonstrated 27 ears to have developed an effusion. Next, all middle ear clefts, in random manner, were either injected with heat-killed Streptococcus pneumoniae 1 x 10(6) in 0.1 mL normal saline, injected with 0.1 mL normal saline alone, or received no injection at all. Middle ear effusions were obtained and analyzed for IL-1 beta and TNF alpha by enzyme-linked immunosorbent assay (ELISA). This study demonstrated a significant correlation between IL-1 beta and the presence of an effusion (P < .001). Additionally, increased TNF alpha levels correlated with bacterial component presence (P < .001), i.e., mean TNF alpha level was 108, 10.8, and 0 pg/mL in bacteria, normal saline, and noninjected ears, respectively. These findings would suggest that cytokine expression may relate to specific pathological conditions and that the chinchilla model for otitis media with effusion (OME) could be used to further explore the role of cytokines in OME.

Animals↗

PubMed1994

Interleukin-8 expression in otitis media.

Based on recent studies in the authors' laboratory on the correlation of cytokines and inflammation in otitis media (OM), the authors hypothesized that in chronic otitis media with effusion (COME) interleukin-8 (IL-8) is responsible for 1. the accumulation of leukocytes in the middle ear cleft and 2. in situ leukocyte activation with subsequent tissue damage. Additionally, the authors hypothesized that IL-8 expression is at least in part under the control of interleukin-1 (IL-1) and tumor necrosis factor (TNF). To begin to test this hypothesis, middle ear effusions (MEE) obtained from children ages 2 to 90 months (mean age, 29 months) undergoing tympanostomy tube placement for the presence of these inflammatory cytokines were analyzed. For these studies, IL-8, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and tumor necrosis factor-beta (TNF-beta) were measured in MEE by radioimmunoassay (RIA) or enzyme-linked immunoassay (ELISA). IL-8, IL-1 beta, TNF-alpha, and TNF-beta were present in 92%, 67%, 77%, and 0% of effusions, respectively. The mean (+/- SEM) values for IL-8, IL-1 beta, and TNF-alpha were 4805 (+/- 913) pg/mg, 4076 (+/- 1510) pg/mg, and 163 (+/- 90) pg/mg. Further analysis indicated that levels of IL-8 correlated with IL-1 beta (R2 = .500, P = .000) and TNF-alpha (R2 = .387, P = .023). Thus the authors' studies clearly demonstrate that IL-8 is consistently present in the MEE of children with COME and is strongly correlated with levels of IL-1 beta and TNF-alpha, both known inducers of IL-8 production. These results support the authors' hypothesis that IL-1 beta, TNF-alpha, and IL-8 are intimately involved in the inflammatory cascade in the middle ear and suggest regulation of these cytokines as possible sites of future therapeutic intervention in otitis media with effusion (OME).

Age Factors↗

PubMed1994

Murine model of otitis media with effusion: immunohistochemical demonstration of IL-1 alpha antigen expression.

Recent studies have suggested that cytokines likely play a central role in the formation and maintenance of otitis media with effusion (OME). Currently, there is no immunologically defined animal model for the study of cytokines as they contribute to the formation of OME. In the present study, a murine model of OME, using eustachian tube blockage via an external surgical approach, was developed. The murine model temporal bone histology appears to mimic the histology found in chronic otitis media with effusion in humans. Additionally, using this murine model, interleukin-1 alpha (IL-1 alpha) expression was detected in the middle ear using standard immunohistochemical techniques. IL-1 alpha seemed localized to the epithelial lining of the middle ear as well as 5% to 10% of inflammatory cells. This model should provide the necessary tool to further study the immunologic aspects of OME.

Animals↗

PubMed1993

HTLV-1 antibody class and subclass distribution in African TSP and control populations.

The humoral immune responses in 44 sera from HTLV-1 seropositive African subjects were compared. The sample population was composed of 12 patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), 12 patients with other neurological conditions and 20 asymptomatic carriers. Samples HTLV-1 antigens were tested against all immunoglobulin classes and IgG subclasses, using the Western blot technique with polyclonal and monoclonal antibodies. Whilst IgG reacted with gag, env and tax products for the three groups studied, IgM and IgA were found to react more frequently with HTLV-1 in HAM/TSP patients. For these patients, IgM and IgA were particularly directed against tax and env proteins. Among IgG subclasses, IgG1 was most sensitive to gag, env and tax products reacting in similar proportions in all three groups. IgG2 and IgG4 were apparently not involved. IgG3 was most responsive in HAM/TSP patients. These data are similar to those observed in AIDS patients, LAS and HIV asymptomatic carriers and emphasize the role of HTLV-1 in HAM/TSP.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Heterogeneity in filarial-specific immune responsiveness among patients with lymphatic obstruction.

The relationship between chronic obstructive disease and antifilarial immune responsiveness was studied in the Haitian community of Leogane, where Wuchereria bancrofti is endemic. Differences in sex ratios and in the prevalence of microfilaremia were observed between patients with hydrocele and those with lymphedema or elephantiasis of the lower limb. Only 2 of 84 patients with limb involvement (74 women, 10 men) were microfilaremic compared with 25 of 42 men with hydrocele. Microfilaria-positive men with hydrocele had significantly lower IgG2 and proliferative responses to filarial antigen than did amicrofilaremic men with hydrocele or individuals with lymphedema or elephantiasis. Parasite-specific cellular responses of amicrofilaremic individuals with obstructive disease were greater, although not significantly so, than those of amicrofilaremic asymptomatic members of the community. These results are compatible with the hypothesis that development of obstructive disease of the lymphatics has an immune component in amicrofilaremic persons.

Adolescent↗

PubMed1993

Distortion-product and click-evoked otoacoustic emissions of preterm and full-term infants.

Full-term and preterm infants were evaluated with click-evoked and distortion-product otoacoustic emissions (CEOEs and DPOEs). The CEOEs and DPOEs recorded from each individual ear were analyzed by calculating the root-mean-square levels within half-octave bands. The fail criterion of the OE tests was that the half-octave RMS DPOE or CEOE levels of an ear under test were below the 10th percentile of full-term newborns in two or more bands. The DPOE data were collected from 118 ears of 61 premature babies; 80 (68%) ears passed the DPOE test, 30 (25%) ears without middle ear effusions failed the test, and 8 (7%) ears with effusions also failed. The CEOE data were collected from 128 ears of 65 premature babies; 102 (80%) ears passed the CEOE test, 18 (14%) ears without middle ear effusions failed the test, and 8 (6%) ears with effusions also failed. In 23 of 80 ears (29%) that passed the DPOE test and in 23 of 102 ears (23%) that passed the CEOE test, RMS OE levels of preterm infants were above the 90th percentile of full-term newborns. The analyses of the combined DPOE and CEOE data obtained from a group of 25 ears of full-term newborns and from a group of 72 ears of preterm babies showed statistically significant correlations between the DPOE and CEOE root-mean-square levels in each of the half-octave bands in the 1.4 to 4 kHz region. For 42 preterm infants tested with auditory brain stem response (ABR), specificity was 86% for CEOE and 74% for DPOE. All infants who failed the ABR also failed OE tests. To the best of our knowledge, this study is the first using combined DPOEs, CEOEs, and ABRs for preterm babies. It showed the feasibility of DPOEs and CEOEs for this population.

Acoustic Impedance Tests↗

PubMed1993

Otoacoustic emissions in full-term newborns at risk for hearing loss.

Distortion product otoacoustic emissions (DPOEs) and click-evoked otoacoustic emissions (CEOEs) characteristics of the normal newborn population have been previously reported in the literature. There is little information about DPOE evaluations in the newborn population at risk for hearing loss. The authors now report the DPOE and/or CEOE data from six full-term subjects at risk for hearing loss or with highly suspected hearing loss. These subjects were less than 1 year of age and at risk for hearing loss secondary to a history of hereditary hearing loss, meningitis, hyperbilirubinemia, and ototoxic drug exposure. Audiometric evaluation included auditory brainstem responses (ABR), behavioral observation audiometry, and tympanometry. The CEOEs and DPOEs were found to be decreased or absent in the subjects with suspected hearing loss secondary to cochlear pathology; they were found to be normal in a subject with a suspected central hearing loss. This study's data suggest that otoacoustic emissions when combined with ABR can provide a frequency-specific evaluation of cochlear function and help determine the anatomic site of a pathologic lesion.

Acoustic Impedance Tests↗

PubMed1992

Studies on the molecular pharmacology of GR63178A. A novel pentacyclic pyrolloquinone anticancer drug.

GR63178A (NSC D611615) is the second pentacyclic pyrolloquinone to be evaluated clinically as an anticancer drug. Its mechanism of action is unknown but may be related either to its quinone group or planar ring system. In this report we have investigated the ability of GR63178A to bind non-covalently to DNA, inhibit topoisomerase II and undergo reduction to reactive free radical species. Using two DNA duplexes, a 12-mer oligonucleotide which is a preferred sequence for minor groove binders and a hexamer which is a preferred sequence for intercalators, no evidence of significant binding with GR63178A was found. Neither GR63178A nor GR54374X (its 9-hydroxy metabolite) inhibited purified human topoisomerase II in a decatenation assay. Free radical chemistry was studied by both pulse radiolysis and ESR spectroscopy as well as by in vitro drug incubations with NADPH-fortified rat liver microsomes and purified cytochrome P450 reductase. The one-electron reduction potential of GR63178A was -207 mV +/- 10 which is much more positive than other quinone-containing anticancer drugs such as doxorubicin, mitomycin C and mitozantrone. GR63178A underwent enzyme-catalysed quinone reduction more readily than doxorubicin but produced significantly fewer reactive oxygen species. No evidence was detected of drug-induced, radical-mediated DNA damage in vitro using pBR322 plasmid DNA. Disproportionation of the GR63178A semi-quinone free radical proceeded with a rate constant of 1 x 10(9) M-1 sec-1 under anaerobic conditions, one order of magnitude faster than doxorubicin. The preferential disproportionation of the semi-quinone may explain our inability to detect a free radical signal by ESR. The hydroquinone of GR63178A was stable and exhibited strong visible absorption with a bathochromic shift of 120 nm over the parent drug. These unusual properties may be due to the hydroquinone undergoing a form of keto-enol tautomerization. Thus, GR63178A free radical formation does not appear to result in significant drug activation. In conclusion, GR63178A is unlikely to mediate its antitumour activity by DNA binding, topoisomerase II inhibition or free radical formation in direct contrast to similar anthracycline- and anthraquinone-based anticancer drugs.

Animals↗

PubMed1992

Demonstration of interleukin 6 in middle ear effusions.

In response to infection in the middle ear, inflammatory cells produce cytokines--potent regulators and mediators of the immune response. In an earlier study, we demonstrated that levels of the cytokine interleukin 1 were higher in middle-ear effusions from younger children, while levels of the cytokine tumor necrosis factor were higher in middle-ear effusions from older children and in those requiring tympanostomy on multiple occasions. In this study, we evaluated middle-ear effusions for levels of the cytokine interleukin 6. Activities of interleukin 6 include stimulation of bone erosion and production of antibodies and fever. Using an enzyme-linked immunosorbent assay system, significant levels of interleukin 6 (greater than 0.2 pg/mL) were found in 14 (36%) of 39 middle-ear effusions from 25 children with otitis media with effusion. The mean (+/- SE) level of interleukin 6 in middle-ear effusions was 173.9 +/- 74.7 pg/mg of total protein. Like interleukin 1, levels of interleukin 6 were higher in younger children. Tumor necrosis factor may be an important regulator of the local immune response in the middle-ear cleft during persistence of otitis media with effusion, while interleukin 1 and interleukin 6 may be important regulators during the early stages of otitis media with effusion.

Child, Preschool↗

PubMed1991

Distortion-product and click-evoked otoacoustic emissions in healthy newborns.

Distortion-product otoacoustic emissions (DPOEs) are believed to provide frequency-specific information about cochlear function. The DPOEs have been reported in the adult population but have not been reported previously in the neonatal population. We recorded DPOEs from a group of healthy full-term newborn human subjects (35 ears) to establish the characteristics of these emissions in the newborn population. To our knowledge, this is the first study of DPOEs in newborns. The "DPOE audiograms" from the newborns tested revealed characteristics qualitatively similar to those seen in adults with normal hearing. This study demonstrates the feasibility of DPOE measurements among newborns and provides a normal baseline for this age group, thus fulfilling a necessary step toward the development of an objective, noninvasive frequency-specific test of cochlear function. Click-evoked otoacoustic emissions were also recorded from the newborn population and compared with click-evoked otoacoustic emissions from adults. The spectrum of the click-evoked emissions was variable and individualistic, similar to findings previously reported in adult subjects. The click-evoked otoacoustic emissions of the newborns had a higher overall level and contained stronger high-frequency (4.5 to 6 kHz) spectral components than those of the adults. We also found that the low-frequency components of the click stimulus spectrum were attenuated in the neonatal ears exhibiting a high-pass slope below about 2.5 kHz, whereas the stimulus spectrum was nearly flat in this frequency region in adult ears.

Acoustic Stimulation↗

PubMed1991

Frontal-lobe contribution to recency judgements.

Three recency-discrimination tasks (involving concrete words, representational drawings and abstract paintings) were administered to 117 patients who had undergone unilateral cortical removals, and to 20 normal control subjects. Frontal or anterior temporal-lobe excision did not impair simple item recognition, and neither left nor right anterior-temporal lobectomy affected recency judgements on any task. In contrast, excisions that encroached on the mid-lateral frontal cortex impaired verbal recency judgements, the deficit being mild after right frontal lobectomy. Patients with right frontal-lobe removals showed the greatest impairment in recency discrimination on the two pictorial tests. The results provide evidence for hemispheric specialization related to the nature of the stimulus material and some support for a functional role for the left mid-lateral frontal cortex in verbal recency judgements.

Adolescent↗

PubMed1991

Contribution of the right frontal lobe to the encoding and recall of kinesthetic distance information.

Sixty-two patients with unilateral temporal- or frontal-lobe excisions and 16 normal control subjects were tested on a kinesthetic task, which required the monitoring of peripheral feedback in order to duplicate the distance of examiner-defined arm movements. Temporal lobectomy did not interfere with performance. Patients with left frontal-lobe or small right frontal-lobe excisions also performed normally, whereas those with large right frontal-lobe removals were impaired, the deficit being equal for the two arms. The results point to an important role played by the right frontal lobe in the monitoring of kinesthetic feedback both during the presentation of the movements and during the recall attempt.

Adolescent↗