Mycoplasma corogypsi-associated polyarthritis and tenosynovitis in black vultures (Coragyps atratus).

Three wild American black vultures (Coragyps atratus) were presented to rehabilitation centers with swelling of multiple joints, including elbows, stifles, hocks, and carpal joints, and of the gastrocnemius tendons. Cytological examination of the joint fluid exudate indicated heterophilic arthritis. Radiographic examination in 2 vultures demonstrated periarticular soft tissue swelling in both birds and irregular articular surfaces with subchondral bone erosion in both elbows in 1 bird. Prolonged antibiotic therapy administered in 2 birds did not improve the clinical signs. Necropsy and histological examination demonstrated a chronic lymphoplasmacytic arthritis involving multiple joints and gastrocnemius tenosynovitis. Articular lesions varied in severity and ranged from moderate synovitis and cartilage erosion and fibrillation to severe synovitis, diffuse cartilage ulceration, subchondral bone loss and/or sclerosis, pannus, synovial cysts, and epiphyseal osteomyelitis. No walled bacteria were observed or isolated from the joints. However, mycoplasmas polymerase chain reactions were positive in at least 1 affected joint from each bird. Mycoplasmas were isolated from joints of 1 vulture that did not receive antibiotic therapy. Sequencing of 16S rRNA gene amplicons from joint samples and the mycoplasma isolate identified Mycoplasma corogypsi in 2 vultures and was suggestive in the third vulture. Mycoplasma corogypsi identification was confirmed by sequencing the 16S-23S intergenic spacer region of mycoplasma isolates. This report provides further evidence that M. corogypsi is a likely cause of arthritis and tenosynovitis in American black vultures. Cases of arthritis and tenosynovitis in New World vultures should be investigated for presence of Mycoplasma spp, especially M. corogypsi.

Postexposure prevention of progressive vaccinia in SCID mice treated with vaccinia immune globulin.

A recently reported case of progressive vaccinia (PV) in an immunocompromised patient has refocused attention on this condition. Uniformly fatal prior to the licensure of vaccinia immune globulin (VIG) in 1978, PV was still fatal in about half of VIG-treated patients overall, with a greater mortality rate in infants and children. Additional therapies would be needed in the setting of a smallpox bioterror event, since mass vaccination following any variola virus release would inevitably result in exposure of immunocompromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support the licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia virus-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia virus-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if left untreated. Postexposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most of the mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most of the animals, even when initiated 7 days postinfection. These results support the possibility that combination treatments may be effective in humans and support using this SCID model of PV to test new antibody therapies and combination therapies and to provide further insights into the pathogenesis and treatment of PV.

Intravenous immunoglobulin products contain neutralizing antibodies to vaccinia.

BACKGROUND AND OBJECTIVES: Individuals with primary or secondary immune-deficiency diseases may be at risk for vaccinia infection if widespread smallpox-immunization programmes are implemented in the United States of America (USA) for bioterrorism preparedness. The objective of this study was to determine whether commercial immune globulin (intravenous, human) products contain biologically active antibodies to vaccinia that have the potential to protect people, with immune deficiencies, from complications of vaccinia. MATERIALS AND METHODS: Eight currently United States (US)-licensed and two European intravenous immunoglobulin (IVIG) products were tested in a vaccinia plaque-reduction neutralization assay. The in vivo activity of five of these lots was assessed in severely immune-deficient mice. RESULTS: All tested products contained neutralizing anti-vaccinia activity, in vitro and in vivo. CONCLUSIONS: The use of IVIG by individuals with inherited or acquired humoral immune deficiencies may provide some protection if they are inadvertently exposed to vaccinia.

Protection from experimental endotoxemia by a recombinant adeno-associated virus encoding interleukin 10.

BACKGROUND: Interleukin 10 (IL-10) is a homodimeric cytokine that shows considerable clinical promise. Adeno-associated virus (AAV) vectors appear increasingly useful for in vivo gene-transfer applications. METHODS: A recombinant AAV type 2 vector encoding human IL-10 (rAAVhIL10) was constructed by using an adenoviral-free, three-plasmid co-transfection. Cytokine production was measured by using an enzyme-linked immunosorbent assay. Endotoxic shock was induced by lipopolysaccharide (LPS) injection. RESULTS: As media from rAAVhIL10-infected COS cells caused a dose-dependent blockade of IL-12 secretion from spleen cells of IL-10 knockout (KO) mice challenged with Brucella abortus, it was clear that vector-derived hIL-10 was biologically active in vitro. Intravenous or intramuscular administration of relatively modest levels of rAAVhIL10 (10(10) genomes) to IL-10 KO mice resulted in hIL-10 secretion into the bloodstream, which, at 8 weeks, gave median serum levels of 0.9 and 0.45 pg/ml, respectively. Acute endotoxic shock led to a 33% mortality rate, and severe morbidity, in control IL-10 KO mice, whereas no mortality and little morbidity were seen in IL-10 KO mice given rAAVhIL10 7 weeks earlier. CONCLUSIONS: The findings demonstrate that a modest dose of rAAVhIL10 administered in vivo provides long-term protection against LPS-induced endotoxic shock in a murine model. Thus, this vector may be useful for clinical applications requiring sustained IL-10 expression, for example in the treatment of several autoimmune diseases.

Ontogeny of Th1 memory responses against a Brucella abortus conjugate.

Protective immune responses to intracellular pathogens such as Brucella abortus are characteristically Th1-like. Recently we demonstrated that heat-killed B. abortus (HKBa), a strong Th1 stimulus, conjugated to ovalbumin (HKBA-OVA), but not B. abortus alone, can alter the antigen-specific cytokine profile from Th2- to Th1-like. In this report we study the ability of a single injection of B. abortus to switch a Th2 to a Th1 response in immature mice. One-day- and 1-week-old mice were given a single injection of B. abortus in the absence or presence of OVA, and at maturity mice were challenged with an allergenic preparation, OVA with alum (OVA-A). B. abortus given without OVA did not diminish the subsequent Th2 response in either age group. In contrast, mice receiving a single injection of B. abortus-OVA at the age of 1 week, but not those injected at the age of 1 day, had reversal of the ratio of OVA-specific Th1 to Th2 cells and decreased immunoglobulin E levels after allergen challenge as adults. Within 6 h both 1-day- and 1-week-old mice expressed interleukin-12 p40 mRNA following either B. abortus or B. abortus-OVA administration. However, only the 1-week-old mice exhibited increased expression of gamma interferon (IFN-gamma) mRNA. The absence of the early IFN-gamma response in 1-day-old mice may explain their inability to generate a Th1 memory response. These results suggest that at early stages of immune development, responses to intracellular bacteria may be Th2- rather than Th1-like. Furthermore, they suggest that the first encounter with antigen evokes either a Th1- or a Th2-like response which becomes imprinted, so that subsequent memory responses conform to the original Th bias. This has implications for protection against infectious agents and development of allergic responses.

IL-12 induction by a TH1-inducing adjuvant in vivo: dendritic cell subsets and regulation by IL-10.

IL-12 induction is critical for immune responses against many viruses and intracellular bacterial pathogens. Recent studies suggest that IL-12-secreting dendritic cells (DC) are potent Th1-inducing APC. However, controversy exists concerning the function of DC subsets. Murine studies have suggested that CD8(+) DC preferentially induce Th1 responses, whereas CD8(-) DC induce Th2 development; in this model, different DC subsets prime different responses. Alternatively, the propensity of DC subsets to prime a Th1 response could depend upon the type of initial stimulus. We used a prototypic Th1-inducing adjuvant, heat-killed Brucella abortus (HKBA) to assess stimulation of DC subsets, relationship between Ag burden and IL-12 production, and down-regulation of DC subset IL-12 production by IL-10. In this study, we show that DC were sole producers of IL-12, although most HKBA uptake was by splenic macrophages and granulocytes. More CD8(-) than CD8(+) DC produced IL-12 after HKBA challenge, whereas only CD8(+) DC produced IL-12 after injection of another Th1-promoting microbial substance, soluble Toxoplasma gondii Ags. Studies in IL-10-deficient mice revealed that IL-10 down-regulates frequency and duration of IL-12 production by both DC subsets. In the absence of IL-10, IL-12 expression is enabled in CD11c(low) cells, but not in macrophages or granulocytes. These findings support the concept of DC as the major IL-12 producers in spleens, but challenge the notion that CD8(+) and CD8(-) DC are destined to selectively induce Th1 or Th2 responses, respectively. Thus, the nature of the stimulating substance is important in determining which DC subsets are activated to produce IL-12.

Immunoglobulin G3 from polyclonal human immunodeficiency virus (HIV) immune globulin is more potent than other subclasses in neutralizing HIV type 1.

Passive antibody prophylaxis against human immunodeficiency virus type 1 (HIV-1) has been accomplished in primates, suggesting that this strategy may prove useful in humans. While antibody specificity is crucial for neutralization, other antibody characteristics, such as subclass, have not been explored. Our objective was to compare the efficiencies of immunoglobulin G (IgG) subclasses from polyclonal human HIV immune globulin (HIVIG) in the neutralization of HIV-1 strains differing in coreceptor tropism. IgG1, IgG2, and IgG3 were enriched from HIVIG by using protein A-Sepharose. All three subclasses bound major HIV-1 proteins, as shown by Western blot assay and enzyme-linked immunosorbent assay. In HIV-1 fusion assays using X4, R5, or X4R5 envelope-expressing effector cells, IgG3 more efficiently blocked fusion. In neutralization assays with cell-free viruses using X4 (LAI, IIIB), R5 (BaL), and X4R5 (DH123), a similar hierarchy of neutralization was found: IgG3 > IgG1 > IgG2. IgG3 has a longer, more flexible hinge region than the other subclasses. To test whether this is important, IgG1 and IgG3 were digested with pepsin to generate F(ab')(2) fragments or with papain to generate Fab fragments. IgG3 F(ab')(2) fragments were still more efficient in neutralization than F(ab')(2) of IgG1. However, Fab fragments of IgG3 and IgG1 demonstrated equivalent neutralization capacities and the IgG3 advantage was lost. These results suggest that the IgG3 hinge region confers enhanced HIV-neutralizing ability. Enrichment and stabilization of IgG3 may therefore lead to improved HIVIG preparations. The results of this study have implications for the improvement of passive immunization with polyclonal or monoclonal antibodies and suggest that HIV-1 vaccines which induce high-titer IgG3 responses could be advantageous.

Immunity and protection against Brucella abortus.

Brucella abortus is an intracellular pathogen that causes disease in cattle and in humans. The response against B. abortus involves the whole gamut of the immune system, from innate to adaptive immunity resulting from stimulation of antigen-presenting cells, NK cells, CD4(+) and CD8(+) T cells, and B cells.

Induction and regulation of Th1-inducing cytokines by bacterial DNA, lipopolysaccharide, and heat-inactivated bacteria.

Th1 immune responses, characterized by production of gamma interferon (IFN-gamma), are associated with protective immunity to viruses and intracellular bacteria. Heat-killed Brucella abortus promotes secretion of Th1-inducing cytokines such as interleukin-12 (IL-12) and IFN-gamma and has been used as a carrier to induce Th1 responses to vaccines. To explore which bacterial constituents could mediate this response and how it is regulated, murine spleen cells were cultured with B. abortus derived DNA, lipopolysaccharide (LPS), or whole killed organisms. Each constituent induced similar, substantial amounts of IL-10. However, only B. abortus and B. abortus DNA induced high levels of IFN-gamma and IL-12. B. abortus and B. abortus DNA-stimulated IL-12 production was maximal by 6 to 18 h, while IL-10 production steadily accumulated over this time period. These kinetics suggested that IL-10 may eventually downmodulate the Th1-like cytokine response to B. abortus and B. abortus DNA, which was confirmed by using neutralizing antibody. In the absence of IL-10, B. abortus LPS induced strong IFN-gamma responses, but IL-12 p70 levels were still undetectable from BALB/c spleen cells. LPS induced IL-12 if the spleen cells were primed with IFN-gamma and IL-10 was neutralized, indicating that LPS can stimulate IL-12 production under the most favorable conditions. Responses to Escherichia coli LPS and DNA mirrored the responses to B. abortus components, suggesting that immune effects observed with these constituents may be generalizable to many microbial species. In vivo experiments demonstrated the same hierarchy of responses for IL-12 production. These findings support the likelihood that microbial components, if used as carriers or adjuvants, can differ substantially in their ability to effect a Th1 response.

Post-traumatic migration and emergence of a novel cell line upon the ependymal surface of the third cerebral ventricle in the adult mammalian brain.

This investigation describes the migration and emergence of significant numbers of what appear to be neuron-like cells upon the surface of the median eminence of the adult rodent neurohypophyseal system of the endocrine hypothalamus following the trauma of hypophysectomy. These cells appear to migrate through the neuropil of the underlying median eminence and emerge in large numbers upon the surface of the third cerebral ventricle within 7 days following hypophysectomy (axotomy) of supraoptic (SON) and paraventricular neurites (PVN) of the adult neurohypophyseal system. Previous investigations have demonstrated regeneration of the neural stem and neural lobe in a variety of mammalian species (Adams et al., J Comp Neurol, 1969;135:121-144; Beck et al., Neuroendocrinology, 1969;5:161-182; Scott et al., Exp Neurol, 1995;131-1:23-39; Scott and Hansen, Vir Med 1997;124:249-261). It also has been demonstrated that the process of regeneration is invariably accompanied by the up-regulation of nitric oxide synthase (NOS), the enzyme that catalyzes arginine to nitric oxide (NO) and that both neurohypophyseal regeneration, as well as migration and emergence of neuron-like cells upon the surface of the adjacent third cerebral ventricle, is associated with the up-regulation of NOS and increased expression of NO. It also has been amply demonstrated that this entire process of neurohypophyseal regeneration and cell migration is completely inhibited by the introduction of the antagonist of nitric oxide, namely, nitroarginine (Scott et al., Exp Neurol, 1995;131-1:23-39; Scott and Hansen, Vir Med, 1997;124:249-261). The emergence and migratory dynamics of this novel cell line upon the floor of the rodent third cerebral ventricle are discussed with respect to the role of the ubiquitous free radical NO and the implications and potential clinical applications of neuronal migration following trauma in the human central nervous system (CNS).

Down-regulation of Th2 responses by Brucella abortus, a strong Th1 stimulus, correlates with alterations in the B7.2-CD28 pathway.

Down-regulation of the Th2-like response induced by ovalbumin-alum (OVA/alum) immunization by heat-killed Brucella abortus was not reversed by anti-IL-12 antibody treatment or in gamma interferon (IFN-gamma) knockout mice, suggesting that induction of Th1 cytokines was not the only mechanism involved in the B. abortus-mediated inhibition of the Th2 response to OVA/alum. The focus of this study was to determine whether an alternative pathway involves alteration in expression of costimulatory molecules. First we show that the Th2-like response to OVA/alum is dependent on B7.2 interaction with ligand since it can be abrogated by anti-B7.2 treatment. Expression of costimulatory molecules was then studied in mice immunized with OVA/alum in the absence or presence of B. abortus. B7.2, but not B7.1, was up-regulated on mouse non-T and T cells following immunization with B. abortus. Surprisingly, B. abortus induced down-regulation of CD28 and up-regulation of B7.2 on murine CD4(+) and CD8(+) T cells. These effects on T cells were maximal for CD28 and B7.2 at 40 to 48 h and were not dependent on interleukin-12 (IL-12) or IFN-gamma. On the basis of these results, we propose that the IL-12/IFN-gamma-independent inhibition of Th2 responses to OVA/alum is secondary to the effects of B. abortus on expression of costimulatory molecules on T cells. We suggest that down-regulation of CD28 following activation inhibits subsequent differentiation of Th0 into Th2 cells. In addition, decreased expression of CD28 and increased expression of B7.2 on T cells would favor B7.2 interaction with CTLA-4 on T cells, and this could provide a negative signal to developing Th2 cells.

Vasoactive intestinal polypeptide in sacral primary sensory pathways in the cat.

Unmyelinated sensory axons in the sacral spinal cord may play a role in bladder reflexes under certain pathological conditions. Previous data suggested vasoactive intestinal polypeptide (VIP) might be contained exclusively in sensory C-fibers, some of which innervate the bladder. This study was undertaken to describe the morphology of these VIP fibers in the sacral cord of the cat. VIP immunoreactivity was confined to unmyelinated axons observed at several levels of the sensory pathway including the dorsal root ganglia, dorsal roots, Lissauer's tract, and the lateral collateral pathway. A combination of light and electron microscopic observations showed VIP-immunoreactive fibers with labeled varicosities and synaptic terminals in laminae I, IIo, V, VII, and X. VIP-immunolabeled varicosities had a mean diameter of 1.6 microm (range = 0.11-7.4 microm, S.D. = 1.01, n = 311) with a small percentage (8%) being relatively large (3-7.4 microm). VIP varicosities contained a mixture of small clear vesicles (CLV) and large dense core vesicles (LDV). Although most varicosities contained a moderate number of LDVs (14.86 LDVs/microm2), some varicosities contained a large number of LDVs, whereas others contained very few. Varicosities that possessed synaptic specializations were classed as terminals and were divided into three morphological classes. Two of these resembled Gray's Type I terminal, whereas a third was similar to the Gray's Type II terminal. There was no consistent relationship between vesicle content of the terminal and the type of synaptic contact it possessed. This study shows that in the sacral spinal cord of the cat, VIP terminals originate only from C-fibers, terminate primarily in laminae I and V, and exhibit a variety of morphologies consistent with heterogeneous origins and functions of the lower urinary tract.

Obstetric history in women with surgically corrected adult urinary incontinence or pelvic organ prolapse.

STUDY OBJECTIVE: To compare obstetric histories of women who had surgical correction of urinary incontinence or pelvic organ prolapse with a similar group who did not. DESIGN: Case control study (Canadian Task Force classification II-2). SETTING: Urban, community-based, private practice teaching hospital. PATIENTS: Four hundred eighty women (age 51.4 +/- 13.0 yrs) who underwent corrective surgery for urinary incontinence, pelvic organ prolapse, or both, and whose obstetric history was obtainable through chart review. The control group was composed of 150 women (age 50.7 +/- 9.6 yrs) having routine screening mammography who completed a questionnaire regarding obstetric, gynecologic, and urologic history. MEASUREMENTS AND MAIN RESULTS: Patients and controls did not differ significantly in terms of age, race, height, weight, body mass index, or smoking history. Women who underwent surgery were of greater parity (2.5 +/- 1.2 vs 2.0 +/- 1.2, p <0.001), less often nulliparous (3% vs 18%, p <0.001), less likely to have had a cesarean delivery (4% vs 15%, p <0.001), and more likely to have had a vaginal delivery (94% vs 77%, p <0.001) than those with no surgery. The odds ratio of patients who had a vaginal delivery compared with controls was 4.7 (2.3-8.3), and that for cesarean delivery was 0.22 (0.11-0.43). Analysis of specific delivery information found that, compared with controls, patients were older by 4 years at time of their first delivery (28.9 +/- 4.9 vs 24.9 +/- 4.9 yrs, p <0.001) and more commonly received epidural analgesia intrapartum (87% vs 40%, p = 0.004). Comparisons within the patient group, categorized by indication for surgery, revealed that women who had surgery for either prolapse alone or for both prolapse and incontinence were most likely to have had vaginal deliveries (85% incontinence alone vs 94% prolapse alone vs 97% both, p <0.001). CONCLUSION: Increased parity, vaginal childbirth, maternal age at time of delivery, and use of epidural analgesia are associated with need for operative correction of pelvic organ prolapse or adult urinary incontinence. Conversely, cesarean delivery is associated with less need for surgical correction of incontinence or pelvic organ prolapse.

HIV peptide conjugated to heat-killed bacteria promotes antiviral responses in immunodeficient mice.

Enhancement of immunity in the setting of HIV infection is difficult owing to loss of functional CD4+ T cells. The MHC class II-deficient mouse (II-/-) environment simulates that of the immunocompromised HIV-infected individual, since these mice have low CD4+ T cell numbers, defective CD4-dependent responses, and are susceptible to opportunistic infection. This strain was used to test whether heat-killed Brucella abortus (BA), covalently conjugated to the V3 peptide of HIV-1 (MN), could elicit anti-HIV responses. V3-BA, but not the T-dependent antigen V3-KLH, induced high levels of IL-12, IFN-gamma, and IL-10 mRNA in both wild-type (WT) and II-/- mice within 24 hr of injection. V3-BA-treated, but not V3-KLH-treated, II-/- mice developed serum IgG and IgA anti-V3 antibodies, with IgG2b and IgG3 as the predominant isotype. Viral neutralization studies, using a syncytium inhibition assay, demonstrated that the antibodies generated by V3-BA in II-/- mice were capable of neutralizing HIV. These experiments demonstrate that a heat-inactivated bacterium such as BA, when used as a carrier, can generate a cytokine environment that results in the production of neutralizing antiviral antibodies in an immunodeficient host. Such strategies could be important in the development of immunotherapies and vaccines for HIV-1 patients.

An intervention for changing high-risk HIV behaviors of African American drug-dependent women.

The purpose of this study was to test the effectiveness of an AIDS education intervention for methadone-dependent, African American women. The women were randomly assigned to experimental (n=107) or control (n=97) group. The experimental group participated in a peer counseling and leadership training program conducted by two experienced nurse counselors over an 8-week period, followed by 8 weeks of reinforcement. The program was designed to reduce AIDS high-risk sexual behavior, increase self-esteem, decrease depressive affect, and increase the women's community-based AIDS prevention communication activities. A total of 130 women completed all phases of the study, including longitudinal Posttests at 2, 4, and 7 months after enrollment. Compared to the control group, there were statistically significant differences in three of the outcomes for the experimental group: The experimental group reported an increased number of safer sexual behaviors (p=.029), showed decreases in depression (p=.001), and reported engaging in more AIDS-related, community-based communication activities regarding prevention (p=.005).

Therapeutic potential of phosphodiesterase type 4 inhibition in chronic autoimmune demyelinating disease.

It was recently demonstrated that selective phosphodiesterase type 4 (PDE4) inhibition suppresses the clinical manifestations of acute experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), and inhibits the production of tumor necrosis factor-alpha (TNF-alpha), a pathogenetically central cytokine. Since the most common presentation of MS in humans is a relapsing-remitting course, we investigated the therapeutic potential of PDE4 inhibition in the relapsing-remitting EAE model of the SJL mouse. Administration of rolipram, the prototypic PDE4 inhibitor, reduced the clinical signs of EAE during both the initial episode of disease and subsequent relapses. In parallel, there was marked reduction of demyelination and also less inflammation throughout the central nervous system (CNS) of rolipram-treated animals. Gene expression of proinflammatory cytokines in the CNS was reduced in most of the rolipram-treated animals. Additional experiments demonstrated that PDE4 inhibition acted principally by inhibiting the secretion of Th1 cytokines, however, the encephalitogenic potential of myelin basic protein-specific T cells was not impaired. Our findings suggest that PDE4 inhibitors are a promising cytokine-directed therapy in chronic demyelinating disease.

Post-traumatic regeneration, neurogenesis and neuronal migration in the adult mammalian brain.

Unlike the peripheral nervous system (PNS), the mammalian central nervous system (CNS) clearly lacks the robust regenerative characteristics and capacity of the former. Despite this fact, two unique regions of the adult mammalian CNS possess such regenerative potential and are capable of active regeneration following injury or structural compromise. These unique areas are the olfactory system and the neurohypophyseal system of the endocrine hypothalamus. Furthermore, it has been clearly demonstrated that primordial neuroblasts regarded as stem cells emerge from the subependymal parenchyma of the walls and floor of the third cerebral ventricle, migrate to the ventricular surface and undergo compensatory synaptogenesis within one week following hypophysectomy. In situ hybridization studies have unequivocally demonstrated that the up-regulation of nitric oxide synthase (NOS) is essential for neural (axonal) regeneration and neuronal (stem cell) migration to occur. Moreover, neuronal migration is reliably inhibited following the administration of the NO antagonist, nitroarginine. The current investigation serves to confirm a remarkable degree of plasticity and regeneration in the adult mammalian neurohypophyseal system coupled with the emergence of primordial neuroblasts that undergo apparent differentiation, migration and compensatory synaptogenesis in response to the up-regulation of NO that occurs following the trauma of hypophysectomy. Evidence from the current investigation appears to confirm that specialized glia of the neurohypophyseal system, the so-called pituicyte, proliferate following hypophysectomy and may serve as a growth matrix or structural template that may target and direct regenerating Supraoptic (SON) and Paraventricular (PVN) axons toward endothelial primordia in the regenerating neural stem and lobe.

Inhibition of primary and recall allergen-specific T helper cell type 2-mediated responses by a T helper cell type 1 stimulus.

Allergic responses are characterized by the production of Ag-specific IgE Abs that are dependent upon Th2-mediated T cell help. We determined whether heat-killed Brucella abortus (BA), an inducer of Th1 responses, could influence the allergic Th2-mediated IgE response to OVA adsorbed to alum (O/A). BA plus O/A, but not O/A alone, induced high levels of mRNA for IFN-gamma and IL-12 promptly after injection. Furthermore, initial treatment with BA plus O/A rendered both BALB/c and C57Bl/6 mice incapable of mounting high IgE responses even after repeated challenges with allergen alone. Long term abrogation of anti-OVA IgE correlated with an increased frequency of IFN-gamma-secreting OVA-specific cells and a decreased frequency of IL-4-secreting OVA-specific cells. Initial treatment with anti-IL-12 prevented BA-induced early IFN-gamma production and secondary IgG2a responses, but did not abrogate IgE suppression. Additionally, secondary OVA-specific IgE responses were down-regulated by BA conjugated to OVA or by BA given with O/A. BA-induced down-regulation of secondary IgE responses was associated with increased frequency of Ag-specific IFN-gamma-secreting cells. These results suggest the possibility that even recall Th2-mediated immune responses can be attenuated if Ag is given with a carrier or adjuvant that induces potent Th1-promoting cytokines.

Courtship behavior and plasma levels of androgens and corticosterone in male marbled salamanders, Ambystoma opacum (ambystomatidae).

We measured plasma levels of testosterone, dihydrotestosterone (DHT), and corticosterone for male marbled salamanders (Ambystoma opacum) collected during the breeding season. Our goal was to ascertain whether steroid levels changed in response to particular reproductive behaviors or laboratory confinement. Six groups of salamanders were examined: (a) MIGRATING, males migrating toward the pond basin during the breeding season; (b) LABORATORY, males kept under confined conditions in the laboratory for 10 days; (c) LAB-FIELD, laboratory males that were later released into seminatural enclosures in the field; (d) COURTING, males from male-female pairs in which the male actively courted the female (and deposited at least one spermatophore); (e) SOLO, males that were individually isolated from conspecifics; and (f) MALE-MALE, males that were placed together in pairs, and in which one male actively courted the other male. In three groups (COURTING, SOLO, and MALE-MALE), salamanders were placed in containers for observation and each male was observed for at least 2 hr prior to a plasma sample being taken. Circulating levels of testosterone, DHT, and corticosterone did not differ significantly for males in these groups. The similarity of androgen levels among the three groups indicated a lack of behaviorally evoked change under experimental conditions designed to reveal a behavior-androgen response. Male A. opacum differ taxonomically from other amphibians showing a behavior-androgen response (three species of toads in the genus Bufo) and also lack amplexus and male-male combat during competition for mates. The effects of confinement were indicated by levels of testosterone and DHT in LABORATORY males that were significantly lower than average levels of males in the following groups: MIGRATING, LAB-FIELD, and MALE-MALE. We inferred that LAB-FIELD males, following their release to seminatural enclosures, were able to regain plasma androgen levels typical of migrating males. This increase is one of very few demonstrations for amphibians of an increase in androgen levels upon release from laboratory confinement. Levels of corticosterone did not differ significantly between males that were active in the field and males that were kept in the laboratory. The similarity of corticosterone levels among these groups differs from the typical pattern of elevated corticosterone and depressed androgen levels in captive amphibians. Maximal corticosterone levels in breeding male A. opacum may act differently than in other species in which chronic elevations inhibit the pituitary-gonadal axis.

AIDS prevention in high-risk African American women: behavioral, psychological, and gender issues.

A three-year longitudinal intervention study was implemented to reduce high-risk drug and sexual behaviors in methadone-dependent African American women. Participants were recruited from four inner-city methadone maintenance programs and randomly assigned either to an eight-week peer counseling and leadership training group or to a control group. The 107 trainees and 97 controls completed pretests and posttests at two, four, and seven months. This paper focuses on final data related to the subjects' sexual beliefs, attitudes, knowledge, and behaviors that put them at risk for HIV/AIDS. Reasons for not using condoms are categorized and discussed. Despite the women's awareness of the seriousness of AIDS, perceived powerlessness to negotiate condom use, negative attitudes about the use of condoms, influence of drugs, and unavailablility of condoms interfered with safer sex practices. The inability of education alone to prevent many high-risk sexual behaviors suggests that more serious consideration be given to expanded distribution of condoms as well as needle exchange programs and legalization of illicit drugs.

PIP: The US Centers for Disease Control report that although African-American women comprise only 12% of the US female population, they account for 56.9% of AIDS cases in women. In 1994, 41% of women with AIDS reported IV-drug use and 38% reported heterosexual contact with a partner at risk for or known to have HIV infection or AIDS. Findings are presented from a 3-year study conducted to assess and reduce high-risk drug and sex behavior among methadone-dependent African-American women in Baltimore, Maryland. Through random assignment, 107 women received 8 weeks of peer counseling and leadership training, and 97 women formed the control group. The women were 20-59 years old of mean age 35.5. 84-90% were unemployed and 16% had been homeless within the preceding 6 months. Subjects completed pretests and post-tests at 2, 4, and 7 months. Despite the women's awareness of the seriousness of AIDS, their perceived powerlessness to negotiate condom use, negative attitudes about condom use, the influence of drugs, and the unavailability of condoms interfered with the practice of safer sex behavior. The authors believe that the inability of education alone to prevent many high-risk sexual behaviors is cause to give more serious consideration to expanding the distribution of condoms as well as needle exchange programs and the legalization of currently illicit drugs.