The relationship between childhood BMI and adult serum cholesterol, LDL, and ankle brachial index.

OBJECTIVE: Effects of childhood overweight may persist into adulthood. We assessed the effect of childhood overweight on cardiovascular disease high risk factor levels in the same participants as adults, after controlling for adult body mass index (BMI) status. DESIGN: A subset of participants in an observational study (Heartwatch) were contacted approximately 26-27 years after initial enrollment to participate in a follow-up study on the long-term effects of childhood overweight. During follow-up, BMI, waist:hip circumference (WHC), blood pressure (BP), serum lipids, and ankle brachial index (ABI) were measured; additional BMI measures throughout childhood were obtained as available from the electronic medical record. Primary outcomes were ABI and serum low density lipoprotein (LDL). SETTING: The 1982 Heartwatch study was conducted with children participants living in Marshfield, Wisconsin; follow-up included original participants who were re-contacted and agreed to be enrolled. PARTICIPANTS: Participants were a stratified random sample of eligible participants in the original 1982 Heartwatch study. Of the original 3106 participants, 647 adult participants completed follow-up exams. RESULTS: Among males with 1982 BMI ≥ 85(th) percentile, adult BMI, WHC, (both P ≤ 0.001), ABI (P = 0.001), total cholesterol (P = 0.01), LDL (P = 0.003) and BP (P < 0.02) were higher in 2008-2009 as compared to males with 1982 BMI < 85(th) percentile. Among females, BMI, BP and WHC (all P < 0.001) were higher in 2008-2009. BMI in 1982 and 2008-2009 were correlated [r = 0.56 (males); 0.58 (females), P < 0.001]. 2008-2009 BMI was more strongly correlated with 2008-2009 measures of ABI (r = 0.16, P = 0.006, males) and high LDL [r = 0.18, P = 0.002 (males); r = 0.11, P = 0.046 (females)]. 1982 BMI was not independently associated with ABI or LDL after adjusting for adult BMI. CONCLUSION: In a cohort studying childhood and adult overweight, childhood BMI was associated with health outcomes relating to cardiovascular disease in adulthood. However, childhood BMI was not independently related to LDL-C or ABI levels in adulthood after accounting for adult BMI. Longitudinal measurements of BMI and other health risk factors were not found to improve accuracy of models for high cardiovascular disease risk factor levels.

Association between obesity and vulnerability and serologic response to influenza vaccination in older adults.

BACKGROUND: Serologic response to influenza vaccination declines with age. Few other host factors are known to be associated with serologic response. Our objective was to determine whether obesity and vulnerability independently predicted serologic response to influenza vaccination. METHODS: Adults ≥ 50 years were recruited during the 2008-2009 influenza season. Subjects provided pre- and post-vaccination sera for measuring antibody titers to 2008-2009 vaccine components. Body mass index (BMI) was calculated as weight (kg)/height (m(2)). Data were collected on vulnerability using the vulnerable elders survey (VES13). Logistic regression evaluated the associations between obesity and vulnerability and the serologic response to vaccination (both seroprotection and seroconversion), adjusting for gender, age, comorbidities, pre-vaccination titer, and site. RESULTS: Mean (± standard deviation) age of 415 study subjects was 65 ± 10 years; 40% were obese. Mean BMI was 29 ± 5.6 kg/m(2); mean VES13 was 1.6 ± 1.8. The proportions of subjects who seroconverted and had seroprotective titers were 40% and 49%, respectively, for A/Brisbane/59 (H1N1); 73% and 80% for A/Brisbane/10 (H3N2); and 34% and 94% for B/Florida. Modified VES-13 (score 0-10, with 10 being most vulnerable) was not associated with seroprotection against H1N1 or H3N2, and VES-13 was directly associated with seroconversion to H1N1 but not H3N2 or B. Obesity (BMI ≥ 30 kg/m(2) vs. BMI 18.5-30 kg/m(2)) was not associated with seroprotection for H1N1 or H3N2; obesity was directly associated with seroconversion to H3N2 but not H1N1 or B. Age was inversely associated with seroprotection and seroconversion against H1N1 and with seroconversion to influenza B. CONCLUSION: Based on this sample of older healthy subjects, there were no consistent relationships between VES 13 or obesity and either seroprotection or seroconversion to three influenza vaccine antigens.

Birth weight and systemic lupus erythematosus.

The fetal environment may be a contributing factor in the etiology of some adult diseases. This study examined whether birth weight, birth length and gestational age are associated with the subsequent development of systemic lupus erythematosus (SLE). The Marshfield Clinic Lupus Registry was searched to identify patients who were born at Saint Joseph's Hospital in Marshfield, Wisconsin, USA. Birth data on each case and five age-, sex-, and race-matched controls were recorded from medical and delivery room register records. Perinatal data were obtained for 23 cases and 115 controls. The unadjusted mean birth weight was similar for cases (3407 +/- 581 g) and controls (3422 +/- 514 g). Birth length was not different between groups. Birth weight adjusted for gestational age, analysed by conditional logistic regression, was not statistically significantly different between groups. We concluded that birth weight and length were similar among SLE cases and controls, suggesting that these perinatal characteristics are not associated with subsequent SLE.

Immunophenotypic characterization of lymphomas from the mediastinum of young ferrets.

OBJECTIVE: To determine the phenotype of naturally developing lymphomas in young ferrets. ANIMALS: 10 ferrets with lymphoma. PROCEDURE: Neoplastic tissues were graded histologically according to the National Cancer Institute's Working Formulation for non-Hodgkin's lymphoma and phenotype was determined by means of immunohistochemical staining. A polyclonal anti-human CD3 and a monoclonal anti-human CD79 antibody were used to classify the lymphomas in situ as T-cell or B-cell origin. Specificity of antibodies was determined by evaluating lymphoid tissue from normal ferrets in situ, which was confirmed by western blot analyses. RESULTS: All 10 ferrets had clinically aggressive tumors, irrespective of the phenotype. Nine ferrets had T-cell lymphoma that extensively involved the mediastinum. Remnants of thymic tissue, indicative of thymic origin, were identified in lymphoma of these 9 ferrets. One ferret had a B-cell multicentric lymphoma without involvement of the mediastinum. CONCLUSIONS: The majority of lymphomas in these young ferrets involved the mediastinum and were of T-cell phenotype. Impact for Human Medicine-There are many similarities between the lymphoma syndrome of ferrets and the condition documented for cats and children with lymphoma of the mediastinal area. CLINICAL RELEVANCE: Differential diagnoses for young ferrets with clinical signs of lethargy or respiratory distress should include T-cell lymphoma of the mediastinum.

Immunodiagnosis of human granulocytic ehrlichiosis by using culture-derived human isolates.

Human granulocytic ehrlichiosis (HGE) is an emerging infection caused by an Ehrlichia species closely related to Ehrlichia equi and Ehrlichia phagocytophila. Recent advances in the isolation and cultivation of this organism have allowed us to develop an immunofluorescence assay (IFA), enzyme immunoassay (EIA), and Western immunoblotting (WB) using HL-60 cell culture-derived human isolates. Antibody was detected in sera from culture-confirmed HGE patients by IFA and EIA, and these samples were reactive when analyzed by immunoblot analysis. HGE patient sera had high antibody titers and did not react with uninfected HL-60 cells. When IFA, EIA, and WB were used to analyze sera from healthy donors or those with a range of other disorders, including infections caused by Ehrlichia chaffeensis, Rickettsia rickettsii, and Coxiella burnetti, no significant cross-reactivity could be detected by EIA or immunoblot analysis with the exception of two of four serum samples from R. rickettsii-infected patients that were reactive by IFA only. Sera from HGE patients did not significantly cross-react in serologic tests for Borrelia burgdorferi. Using sera from patients previously enrolled in two clinical trials of treatment for early Lyme disease, we evaluated a two-step approach for estimation of the seroprevalence of antibodies reactive with the etiologic agent of HGE. On the basis of the immunoblot assay results for sera from culture-confirmed HGE patients, WB was used to confirm the specificity of the antibody detected by EIA and IFA. EIA was found to be superior to IFA in the ability to detect WB-confirmed antibodies to the HGE agent. When EIA and WB were used, 56 (19.9%) patients with early Lyme disease (n = 281) had either specific immunoglobulin M (IgM) or IgG antibodies; 38 patients (13.5%) had IgM only, 6 (2.1%) had IgG only, and 12 (4.3%) had both IgM and IgG. Therefore, Lyme disease patients are at high potential risk for exposure to Ehrlichia. Analysis by immunoblotting of serial samples from persons with culture-confirmed HGE or patients with Lyme disease and antibodies to the agent of HGE revealed a reproducible pattern of the immune response to specific antigens. These samples confirmed the importance of the 42- to 45-kDa antigens as early, persistent, and specific markers of HGE infection. Other significant immunogenic proteins appear at 20, 21, 28, 30, and 60 kDa. Use of the two-test method of screening by EIA and confirming the specificity by WB appears to offer a sound approach to the clinical immunodiagnosis of HGE.

Helicobacter mustelae-associated gastric MALT lymphoma in ferrets.

Gastric lymphoma resembling gastric mucosa-associated lymphoid tissue (MALT) lymphoma linked with Helicobacter pylori infection in humans was observed in ferrets infected with H. mustelae. Four ferrets with ante- or postmortem evidence of primary gastric lymphoma were described. Lymphoma was diagnosed in the wall of the lesser curvature of the pyloric antrum, corresponding to the predominant focus of H. mustelae induced gastritis in ferrets. Two ferrets had low-grade small-cell lymphoma and two ferrets had high-grade large-cell lymphoma. Gastric lymphomas demonstrated characteristic lymphoepithelial lesions, and the lymphoid cells were IgG+ in all ferrets. Lymphoma was confirmed by light chain restriction, which contrasted with the 1.2:1 kappa lambda ratio observed in H. mustelae-associated chronic gastritis. H. mustelae infection in ferrets has been used as a model for gastritis, ulcerogenesis, and carcinogenesis. The ferret may provide an attractive model to study pathogenesis and treatment of gastric MALT lymphoma in humans.

Changing course of growing axons in the optic chiasm of the mouse.

The distribution of retinofugal fibres has been studied by electron microscopy throughout the extent of the developing mouse optic nerve and chiasm at embryonic day (E) 16, in order to determine the course of fibre growth. Growth cones and mature axons, which are randomly distributed in bundles in the extracranial optic nerve, segregate in the juxtachiasmatic optic nerve. Here, growth cones accumulate in subpial regions amongst the endfeet of radial glia, whereas axons lie in the depths of the nerve. Surprisingly, however, growth cones move away from this region toward the ventricular zone in the lateral and midline parts of the chiasm, only to return to subpial regions once more before entering the optic tract, where fibres are again in an age-related order. Superficially, mature axons mingle with growth cones in the chiasm and near the beginning of the optic tract, suggesting that the age-related order begins to be reestablished before growth cones enter the tract. Deep and superficial regions of the pathway were examined in different planes of section. Specialised membrane relationships between retinofugal fibres and radial glial cells were also studied in deep and superficial regions of the lateral part of the chiasm. In addition, the distribution of retinofugal fibre bundles in the adult mouse was looked at by using light microscopy. The changing fibre positions noted in the embryo are maintained in the adult.

Genesis of the frog retinal pigment epithelium.

To examine cell generation in the frog retinal pigment epithelium (RPE), representative developmental stages from tail-bud to adulthood received a single injection of [3H]thymidine. Animals were killed either 24 h or several weeks later; eyes were sectioned and processed by standard autoradiographic procedures and viewed by epi-polarised illumination. The distribution of [3H]thymidine-labelled cells indicated that the RPE is formed throughout life, including in adulthood, by cell addition at the ciliary margin, matching the pattern for the neural retina. In addition, a very small number of peripapillary RPE cells underwent division but only in the adult.

Protective immunity is induced by a Borrelia burgdorferi mutant that lacks OspA and OspB.

A mutant of virulent Borrelia burgdorferi 297 was apparently selected for by long-term storage at 5 degrees C. This mutant was found to lack the plasmid which encodes outer surface protein A (OspA) and OspB. In addition to the loss of the OspA and OspB proteins, the mutant lacked two lipoproteins, of 20 and 7.5 kDa, that were observed in the wild type. Since the mutant was not recovered from the tissues or blood of hamsters injected with the mutant, the mutant was determined to be noninfectious. Hamsters vaccinated with noninfectious mutant 297 were protected completely from challenge with virulent wild-type 297 spirochetes. Prechallenge sera from hamsters vaccinated with mutant 297 lacked antibodies to OspA and OspB, while those from hamsters vaccinated with virulent wild-type 297 or avirulent 297 exhibited antibodies to these proteins. Hamsters vaccinated with virulent wild-type 297 or mutant 297 elicited antibodies to OspC and a 39-kDa protein (P39), whereas hamsters vaccinated with avirulent 297 lacked these antibodies. These results suggest that OspC and/or P39 are important for the development of a protective immune response. Study of this mutant may elucidate factors important to the development of a Lyme disease vaccine.

Intracellular injections of permanent tracers in the fixed slice: a comparison of HRP and biocytin.

Here we describe a method for intracellularly injecting mixtures of the fluorescent dye Lucifer Yellow and the permanent tracers HRP or biocytin into aldehyde-fixed slices of the dorsal lateral geniculate nucleus in young postnatal cats. Lucifer Yellow was used for visual control in the injection procedure and the inclusion of HRP or biocytin allowed the subsequent use of simple histochemical processing to give a permanent record of the injected cells. Both tracer mixtures revealed the dendritic morphology of injected cells. However, HRP was found to be superior to biocytin, in that dendrites were better defined and fine details of cellular morphology such as spines were consistently revealed. Using this technique we were able to demonstrate that the dendritic morphology of geniculate cells is much more mature between birth and 2 weeks than was thought from previous studies using Golgi methods.

Activity of acyclic halogenated tubercidin analogs against human cytomegalovirus and in uninfected cells.

Novel acyclic halogenated tubercidins (4-amino-5-halo-7-[(2-hydroxyethoxy)-methyl]pyrrolo[2,3-d]pyrimidines) were examined for their ability to inhibit human cytomegalovirus (HCMV) in yield reduction assays. 5-Bromo acyclic tubercidin (compound 102) was a more potent inhibitor of virus replication than the chloro- and iodo-substituted analogs (compounds 100 and 104). At a 100 microM concentration, the bromo and chloro compounds were more potent than acyclovir but not ganciclovir. Virus titers were reduced more than 99% by compounds 102 and 104 whereas compound 100 and the equally potent acyclovir reduced titers by only 90%. Quantitation of viral DNA by DNA hybridization demonstrated strong inhibition of HCMV DNA synthesis by these compounds. The most potent inhibitor, compound 102, had a 50% inhibitory (I50) concentration (1.6 microM) comparable to that of ganciclovir (1.8 microM). Cytotoxicity in uninfected human cells was evaluated and revealed the following: cell growth rates slowed markedly in the presence of 10 microM compound 102 whereas the same concentration of compounds 100 and 104 led to only a slight prolongation of population doubling time; these compounds inhibited cellular DNA synthesis but not RNA or protein synthesis, as measured by incorporation of radiolabeled precursors into acid-precipitable macromolecules; flow cytometry indicated that compound 102 was a mid-S phase blocker, and adenosine antagonized the inhibition of [3H]dThd incorporation by compound 102. Together, these results demonstrate that compound 102 is a potent and selective inhibitor of viral and cellular DNA synthesis and that acyclic halogenated pyrrolo-pyrimidine nucleosides may have therapeutic potential.

Synthesis and antiviral activity of some 7-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine analogues of sangivamycin and toyocamycin.

The sodium salt of 4-amino-3-cyanopyrazolo[3,4-d]pyrimidine (1) was condensed with (2-acetoxyethoxy)methyl bromide (2) to provide the corresponding protected acyclic nucleoside, 4-amino-3-cyano-1-[(2-acetoxyethoxy)methyl]-pyrazolo[3,4-d]pyrimid ine (3). Treatment of 3 with sodium methoxide in methanol provided a good yield of methyl 4-amino-1-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine-3- formimidate (4). Treatment of the imidate (4) with sodium hydrogen sulfide gave the thiocarboxamide derivative 5. Aqueous base transformed 4 into 4-amino-1-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine-3- carboxamide (6) in good yield. Treatment of 5 with mercuric chloride furnished the toyocamycin analogue 7. Evaluation of compounds 1, 3-7 revealed that only the heterocycle (1) and the thiocarboxamide acyclic nucleoside (5) were active. Compound 5 was the more potent with activity against human cytomegalovirus and herpes simplex virus type 1.

A microtiter virus yield reduction assay for the evaluation of antiviral compounds against human cytomegalovirus and herpes simplex virus.

Although the virus yield reduction assay is a powerful technique for evaluating the efficacy of antiviral compounds, it is not routinely utilized due to its labor-intensive nature. This procedure was modified, developed, thereby reducing greatly the time and effort required to perform yield reduction assays. Monolayer cultures of mammalian cells were grown in 96-well microtiter tissue culture plates and infected with virus. Test compounds were added and serially diluted directly with the plates. Following a cycle of virus replication, culture lysates were made and serially diluted in a separate set of uninfected cultures grown in microtiter plates. The cultures were incubated, plaques were enumerated in wells containing 5 to 20 plaques, and virus titers were calculated. To illustrate the use of the assay the known antiviral drugs acyclovir and ganciclovir were evaluated using this procedure. Ninety percent inhibitory concentrations for the respective drugs were 3 microM and 0.7 microM against herpes simplex virus type 1 and 60 microM and 1 microM against human cytomegalovirus.

Retinofugal projections in a marsupial, Tarsipes rostratus (honey possum).

We examined the mature retinal projections of the honey possum, Tarsipes rostratus, an Australian, diprotodont marsupial, using uni-ocular injections of horseradish peroxidase and tetramethylbenzidine processing. The suprachiasmatic nucleus, medial, lateral and dorsal terminal nuclei of the accessory optic tract, pretectal nuclei and superior colliculus received bilateral retinal input. Contralateral input only was observed in the lateral posterior nucleus. The pattern of input to these regions was essentially similar to that seen in other marsupials. Cyto-architectural examination of the dorsal lateral geniculate nucleus (dLGN) indicated that 5 laminae were present in the alpha-segment, but the beta-segment appeared to lack lamination. Input to the dLGN was bilateral, overlapping considerably, and was organised in a laminar fashion with 7 and 3 terminal bands in the alpha- and beta-segments, respectively. The monocular segment accounted for 12% of the total volume of the dLGN. In the alpha-segment, 2 terminal bands each received exclusively contralateral or ipsilateral input and 3 bilateral input. In the beta-segment, 2 terminal bands received bilateral and 1 contralateral input. The volumes of the nucleus receiving contralateral and ipsilateral input were 77 and 54% of the total, respectively. A marked overlap of input from the two eyes is an unusual feature for a diprotodont marsupial and has previously been seen only in the feathertail glider. Our findings for the dLGN are of interest in the light of recent serological and taxonomic studies which suggest a close link between the feathertail glider and the honey possum.

Expanded retinofugal projections to the dorsal lateral geniculate nucleus and superior colliculus after unilateral enucleation in the wallaby Setonix brachyurus, quokka.

We removed one eye of quokkas either neonatally, before retinal innervation of visual centres, or at 35-40 days postnatal, when projections overlap bilaterally and are more widespread than in the adult. Retinal projections to the dorsal lateral geniculate nucleus and superior colliculus at postnatal day 100 were demonstrated following anterograde transport of horseradish peroxidase. There were significant reductions in the size of the dorsal lateral geniculate nucleus and superior colliculus ipsilateral to the remaining eye. However, the extent of retinofugal projections was markedly expanded in comparison to the normal input from one eye. Unexpectedly, projections were expanded to similar extents in the two series of enucleated animals although ipsilateral labelling appeared more dense after neonatal enucleation. In controls, label was restricted to eye-specific regions but in enucleated animals there were no label-free zones. Nevertheless the alpha laminae remained distinct in the dorsal lateral geniculate nucleus of enucleated animals. Our findings suggest that binocular interactions are necessary for the segregation and refinement of visual projections but not for the formation of the alpha laminae.

Retinal ganglion cell number is unchanged in the remaining eye following early unilateral eye removal in the wallaby Setonix brachyurus, quokka.

The expanded visual projections which develop after unilateral eye removal have been associated in some studies, but not in others, with the survival of more ganglion cells than normal in the remaining eye. We have addressed this issue using the small wallaby Setonix brachyurus, quokka. Moreover to determine whether more ganglion cells survive when the eye is removed at a very early stage, we have compared the effect of enucleations at two ages. These were within 3 days of birth, before optic fibres innervate visual centres, and at 35-40 days postnatal, when visual projections are exuberant. At 100 days postnatal, retinal ganglion cells were retrogradely labelled from primary visual centres and tracts with horseradish peroxidase, allowing 24 h for transport. Numbers of ganglion cells were similar between animals enucleated as neonates (X = 231,000, n = 3) and at 35-40 days postnatal (X = 218,000, n = 4). These results were comparable to those of controls (X = 227,000, n = 5). Distributions of ganglion cells were also essentially similar in experimental and control series. However, mean ganglion cell soma diameter was significantly greater than normal in both the area centralis and temporal retina after neonatal enucleation. Our results indicate that in enucleated quokkas increased ganglion cell numbers do not underlie enhanced retinofugal projections.

Synthesis, cytotoxicity, and antiviral activity of certain 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidine nucleosides related to toyocamycin and sangivamycin.

A number of 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidine derivatives related to the nucleoside antibiotics toyocamycin and sangivamycin were prepared and tested for their biological activity. Treatment of the sodium salt of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine (1) with (2-acetoxyethoxy)methyl bromide (2) afforded a mixture of 4-amino-6-bromo-5-cyano-7-[(2-acetoxyethoxy)methyl]pyrrolo[2,3-d] pyrimidine (3) and the corresponding N1 isomer. Debromination of this mixture gave the corresponding 4-amino-5-cyano-7-[(2-acetoxyethoxy)-methyl]pyrrolo[2,3-d]pyrimidi ne (4) and 4-amino-5-cyano-1-[(2-acetoxyethoxy)methyl]pyrrolo[2,3-d]pyrimidin e (5). Deacetylation of 4 and 5 furnished 4-amino-5-cyano-7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidine (6) and the corresponding N1 isomer (7), respectively. The sites of attachment for the acyclic moiety for 6 and 7 were assigned on the basis of UV spectral studies as well as 13C NMR spectroscopy. Conventional functional group transformation of 6 provided a number of novel 5-substituted derivatives (8-10), including the sangivamycin derivative 8. The methyl formimidate derivative 10 was converted to the thioamide derivative 11 and the carbohydrazide derivative 12. Compounds 6 and 8-12 were tested for cytotoxicity to L1210 murine leukemic cells in vitro. None of these compounds caused significant inhibition of cell growth. Evaluation of compounds 4 and 6-12 for activity against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) revealed that only the thioamide (11) was active. It inhibited HCMV but not HSV-1 at concentrations producing only slight cytotoxicity in human foreskin fibroblasts (HFF cells) and KB cells.

Synergistic interaction of 2',3'-dideoxycytidine and recombinant interferon-alpha-A on replication of human immunodeficiency virus type 1.

Effective treatment of infections with human immunodeficiency virus type 1 (HIV-1) may require a combination of antiviral drugs that act by different mechanisms. We report that the combination of 2',3'-dideoxycytidine (ddCyd) and recombinant interferon-alpha-A (rIFN-alpha-A) acts synergistically against HIV-1 replication in vitro. Various cell types (peripheral blood leukocytes, a CD4-positive T cell line, and two monocyte-macrophage lines) have been studied. For each set of dose-effect data, the degree of drug interaction was quantitatively assessed with the median-effect principle and the isobologram equation by using a computer analysis. Under various culture conditions using several concentrations of drugs, multiplicities of infectious virus, and assay systems, antiviral synergism was consistently observed against HIV-1 replication without enhanced cell toxicity. Synergism was seen at concentrations as low as 0.02 microM ddCyd plus 4 U of rIFN-alpha-A/mL or 0.01 microM ddCyd plus 8 U of rIFN-alpha-A/mL, whereas 10-fold higher concentrations were usually required to achieve similar effects with single drugs.

The accessory optic system of the wallaby, Setonix brachyurus: anatomy in normal animals and after early unilateral eye removal.

We have traced primary visual projections to nuclei of the accessory optic system in the mature wallaby, Setonix brachyurus, the "quokka," following unilateral intraocular injections of horseradish peroxidase. The organization of pathways and nuclei is similar to that of other marsupials and to that of eutherian mammals. The dorsal, lateral and medial terminal nuclei receive bilateral input, though nuclei ipsilateral to the injected eye are weakly labelled in comparison with their contralateral counterparts. We also report on the accessory optic system in animals which were unilaterally enucleated neonatally or at postnatal day 35. At maturity in enucleated animals, ipsilateral projections to all nuclei of the accessory optic system are more densely labelled than normal. This exuberance is more pronounced in neonatally enucleated animals than in those enucleated at the later stage.