HIV-1-specific cell-mediated immune responses induced by DNA vaccination were enhanced by mannan-coated liposomes and inhibited by anti-interferon-gamma antibody.

The adjuvant effect of mannan-coated liposomes on human immunodeficiency virus type-1 (HIV-1) DNA vaccine and the mechanism of this enhancement were studied. Coating of cationic liposomes with mannan significantly enhanced the ability of this vaccine to induce an HIV-specific delayed-type hypersensitivity (DTH) response. HIV-specific cytotoxic T-cell (CTL) activity elicited by DNA vaccination was also significantly enhanced with the mannan-liposome cocktail. This mannan-liposome-mediated activity was greatly inhibited by in vivo injection of anti-interferon (IFN)-gamma antibody, which suggests that IFN-gamma plays an important role in this HIV-specific immune response. The results of both isotype-specific antibody and cytokine analysis revealed that mannan-liposome-mediated DNA vaccination enhances Th1-mediated immunity.     

Osteosarcoma occurring in osteogenesis imperfecta

We describe a case history of a 24-year-old male with osteogenesis imperfecta (OI) who developed osteosarcoma of the left thigh. High-dose ifosfamide therapy caused marked tumor regression of multiple lung metastases. Immunohistochemically, the tumor cells were diffusely positive for the p53 protein. Mutation of the p53 gene was not detected by direct genomic sequencing of exons 4–8. The radiographic characteristics, including irregularly distributed osteolytic lesions and cortical discontinuity, should not be confused with hyperplastic callus formation, a benign process. A biopsy is critical to establish the differential diagnosis between osteosarcoma and common hyperplastic callus formation in OI; however, it must be applied with great care.     

Induction of HIV-specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV-capturing nanospheres in macaques

We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and that intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody response in mice. In this study, to evaluate the protective effect of immunization, each three macaques was intranasally immunized with Con A-NS or inactivated simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) and then intravaginally challenged with a pathogenic virus, SHIV KU-2. After a series of six immunizations, vaginal anti-HIV-1 gp120 IgA and IgG antibodies were detected in all SHIV-NS-immunized macaques. After intravaginal challenge, one of the three macaques in each of the Con A-NS- and SHIV-NS-immunized groups was infected. Plasma viral RNA load of infected macaque in SHIV-NS-immunized macaques was substantially less than that in unimmunized control macaque and reached below the detectable level. However, it could not be determined whether intranasal immunization with SHIV-NS is effective in giving complete protection against intravaginal challenge. To explore the effect of the SHIV-NS vaccine, the remaining non-infected macaques were rechallenged intravenously with SHIV KU-2. After intravenous challenge, all macaques became infected. However, SHIV-NS-immunized macaques had lower viral RNA loads and higher CD4(+) T cell counts than unimmunized control macaques. Plasma anti-HIV-1 gp120 IgA and IgG antibodies were induced more rapidly in the SHIV-NS-immunized macaques than in the controls. The rapid antibody responses having neutralizing activity might contribute to the clearance of the challenge virus. Thus, SHIV-NS-immunized macaques exhibited partial protection to vaginal and systemic challenges with SHIV KU-2.     

A case of subacute cerebral infarction demonstrating hyperemia and crossed cerebellar diaschisis in I-123 IMP SPECT

SPECT with N-isopropyl-p-[I-123]iodoamphetamine were performed in a 81-year-old man with cerebral infarction. In the subacute phase, the radioactivity was increased in the infarct area where fogging effect and remarkable contrast enhancement was demonstrated in X-ray CT. The contralateral cerebellar hemisphere showed reduced activity due to crossed cerebellar diaschisis (CCD). In the chronic phase, the decrement of the activity in the infarct was observed. Increased activity in the subacute phase was thought to reflect the hyperemia in the infarct, while CCD suggested the decreased metabolic activity in the lesion. The coexistence of the hyperemia and the CCD indicates flow and metabolic uncoupling, which means "luxury perfusion". This case was also thought to demonstrate atypical findings of CCD in SPECT imaging.     

Bathoiodopsin, a primary intermediate of iodopsin at physiological temperature.

Measurement of the primary photochemical reaction of iodopsin, a chicken red-sensitive cone visual pigment, was carried out at room temperature by using picosecond (ps) laser photolysis. Excitation of iodopsin with a ps green pulse (pulse width, 21 ps) caused the instantaneous formation of a bathochromic product, which was stable on a ps time scale. This product may correspond to "bathoiodopsin," which was detected by low-temperature spectrophotometry. Although bathoiodopsin produced at the temperature of liquid nitrogen or helium reverted to the original pigment (iodopsin) on warming (above -170 degrees C), the bathoiodopsin produced at physiological temperature decayed to all-trans-retinal and R-photopsin (the protein moiety of iodopsin) presumably through several intermediates. The absorption maximum of bathoiodopsin at room temperature was at 625 nm, a wave-length slightly shorter than that measured at low temperature (lambda max, 640 nm). The extinction coefficient of bathoiodopsin at room temperature was lower than that at low temperature and close to that of the original iodopsin at room temperature.     

Deposition of extracellular matrix on silicone intraocular lens implants in rabbits

Purpose: To examine the deposition of extracellullar matrix on silicone intraocular lenses (IOLs) implanted experimentally into rabbit eyes by electron microscopy and to determine the immunolocalization of extracellular matrix components, including collagen types and cellular fibronectin, on these IOLs. Methods: We performed phacoemulsification and aspiration of the crystalline lens and implanted a foldable silicone IOL in the capsular bag of one eye of each of 26 adult albino rabbits under general anesthesia. After 8 weeks the animals were killed and the eyes were enucleated. The silicone IOLs were processed for electron microscopy and for immunohistochemical detection of collagen types I, III, and IV and cellular fibronectin. Results: Electron microscopy revealed deposition of a presumed cell matrix complex on the optic portion of all silicone IOLs, as well as the adhesion of presumed macrophages and foreign-body giant cells. Cellular deposits showed immunoreactivity for cellular fibronectin. Fibrous or membranous deposits exhibited immunoreactivity for cellular fibronectin and collagen types I and III. A few type IV collagen-immunoreactive deposits were also seen. Conclusion: Deposits of extracellular matrix components were observed on silicone IOLs. These deposits may form the scaffolding for the adhesion and proliferation of cells. These matrix components appeared to be the products of cells adhering to the surfaces of IOLs, including lens epithelial cells, macrophages and foreign-body giant cells, indicating that the process of granulation was incomplete.     

Influence of ETR-p1/f1 antisense peptide on endothelin-induced constriction in rat renal arcuate arteries

1. This study set out to examine the endothelin receptor subtypes mediating vasoconstriction in the rat renal arcuate artery. This was done in isolated vessels 120–200 μm in diameter, incubated with a selective agonist and the novel ‘antisense'' peptide to part of the human endothelin_A receptor.
2. Groups of vessels (n=6) were incubated with increasing concentrations of endothelin-1 (ET-1), from 1 to 100 nM, which caused a 65% maximal contraction at the highest dose with an pEC₅₀ of 8.16±0.11 M. By contrast, in six other vessels sarafotoxin 6c over the same dose range gave a minimal contraction (around 5% of maximum).
3. Preincubation of six vessels with the antisense peptide ETR p₁/f1 at 1 μM had no effect on the ET-1 induced vasoconstriction, in terms of displacement of the concentration-response curve or the maximal tension achieved by the agonist. In the six vessels exposed to 4 μM ETR p₁/f1, there was a significant shift of the concentration-response curve and a lower pEC₅₀ at 7.78±0.09 M (P<0.05). At the highest concentrations of ETR p₁/f1, there was a marked suppression of all responses to ET-1, which at the maximal concentrations tested, 0.1 μM, only reached some 10% of the maximal achievable contraction.
4. Increasing ET-1 concentrations up to 2 μM in vessels incubated with 40 μM ETR-p₁/f1 showed that the blockade could be overcome and that the relationship was shifted to the right (P<0.001) by approximately one log unit with a pEC₅₀ of 7.13±0.11 M. A Schild plot of the data indicated the antagonist to be acting competitively at a single population of receptors.
5. At the highest concentrations tested, 40 μM, ETR-p₁/f1 had no effect on noradrenaline-induced contractions, indicating a lack of non-specific actions.
6. Together, these data suggest that at the rat renal arcuate artery the endothelin_A receptor is the predominant functional receptor mediating contraction. Furthermore, this study has shown the potential usefulness of this novel type of ‘antisense'' peptide in blocking receptor activation.