Aloe polymannose enhances anti-coxsackievirus antibody titres in mice.

Aloe polymannose (AP), a high mannose biological response modifier (BRM) purified from the Aloe barbadensis Miller plant, was tested for activity in enhancing antibody titres against coxsackievirus B3 (CVB3) and CVB3-induced myocarditis in murine models of the disease. Inoculation of mice with AP over a range of three nontoxic doses and in varying schedules did not reduce virus titres in heart tissues or ameliorate virus-induced cardiopathological alterations during acute disease. However, this BRM was found to significantly enhance titres of anti-CVB3 antibodies produced during acute infection of three strains of mice with CVB3. Simultaneous intraperitoneal inoculation of AP at a dose of 0.5 mg/kg body weight per mouse with purified CVB3 significantly increased ELISA titres of anti-CVB3 antibodies and the proportion of mice with these titres, compared with similar parameters in mice inoculated only with CVB3. The data conclusively show that AP can immunopotentiate antibody production against capsid protein epitopes of a nonenveloped picornavirus and suggest this BRM (AP) might be of benefit in enhancing antibody titres against other enteroviruses during a natural infection and poliovirus vaccine strains.

Expression of surfactant protein mRNA in normal and neoplastic lung of B6C3F1 mice as demonstrated by in situ hybridization.

The localization of surfactant protein (SP), A, B, C, and D mRNAs was examined in B6C3F1 mice in the normal lung, and in a range of spontaneous proliferative lung lesions using nonisotopic in situ hybridization (ISH). The aim was to develop diagnostic markers, and if possible, throw further light on the histogenesis of these lesions. Tissues from 21 animals were examined, the lesions studied were: 4 alveolar epithelial hyperplasias, 12 alveolar/bronchiolar (A/B) adenomas, and 5 A/B carcinomas. Lung metastases of hepatocellular carcinoma (HCC) were used as controls. In the nonneoplastic lung, staining for SP A, B, and C mRNA was observed in normal and hyperplastic type II cells but not in the bronchiolar epithelium. SP mRNAs were present in all lung tumors, with SPs A, B, and C being coexpressed in 10/12 (83%) of adenomas and 4/ 5 (80%) of carcinomas in both solid and tubulopapillary areas. No signals for SP D mRNA were noted in normal or neoplastic lung. Additionally, no staining for any SP transcript was observed in the HCC metastases examined. In summary, ISH for SP A, B, or C mRNA was a helpful aid in the diagnosis of proliferative lesions of the murine lung, enabling differentiation from hepatocellular metastases. Furthermore, this work provides strong support for the proposal that spontaneous lung tumors in B6C3F1 mice are of alveolar, not bronchiolar origin, and consistently show type II cell differentiation. We suggest that such tumors should be referred to as alveolar adenomas and carcinomas.

A glyconutritional mixture (Ambrotose®) provides some amelioration to mice with coxsackievirus-induced pancreatitis.

Challenge of adolescent male CD-1 mice with a coxsackievirus B3 (CVB3) strain (CVB3m) induces mild to severe destruction of pancreatic acinar cells, but causes no deaths and does not induce hyperglycemia. A weekly parenteral (intraperitoneal) administration of a glyconutritional mixture (Ambrotose® to virus-challenged mice was assessed to determine if there were any benefits to recovery over an eight month period. Virus-challenged mice showed a significant weight loss over the initial five weeks of the experiment, but injection of Ambrotose® to similar virus-challenged mice restored the total body weight to levels found in normal mice. Normal mice given Ambrotose® exhibited a small weight gain. Mice given Ambrotose® showed reduced severity of pancreatitis, as evidenced by significant reductions in percentages of pancreatic acinar cells destroyed and proportion of sections of pancreata with destroyed acinar cells, compared to virus control-mice not injected with Ambrotose®. Statistical analyses of the extent of acinar cell pathology in all virus-challenged mice showed that Ambrotose® contributed significantly to recovery of the acinar cell population in virus-inoculated mice. Anti-viral antibody titers were not affected by Ambrotose® injections. One potential mechanism to explain the benefits derived from Ambrotose® injections came from studies of antioxidant levels of glutathione in splenic macrophages/monocytes. Whereas CVB3 challenge of mice reduced glutathione levels in the latter cells, Ambrotose® injections to virus-challenged mice restored glutathione levels to those found in normal mice. In summary, most but not all mice derived benefits from Ambrotose® injections, i.e. a reduction in pathology in the pancreas and restored levels of the antioxidant glutathione in macrophages/monocytes. Higher doses of Ambrotose® could provide greater benefits for more mice, a study for the future.

In situ hybridization demonstration of albumin mRNA in B6C3F1 murine liver and hepatocellular neoplasms.

In situ hybridization was used to detect albumin mRNA in normal liver and hepatocellular neoplasms in 20 male B6C3F1 mice between 17 and 24 months of age. Positive signals for albumin were observed consistently in the cytoplasm of hepatocytes in normal liver, particularly in periportal areas. No signals were observed in other cells, such as Kupffer's cells, mesenchymal cells, or bile duct epithelium. Of hepatocellular adenomas, 11/11 (100%) stained positively for albumin mRNA, whereas 14/15 (93%) of primary hepatocellular carcinomas showed positive expression. Albumin mRNA was also detected in extrahepatic metastases of hepatocellular carcinoma, including 9/15 (60%) of pulmonary neoplasms and 5/12 (42%) of metastases at other sites. The pulmonary metastases of hepatocellular carcinoma frequently exhibited a glandular, papillary, or sarcomatous histologic appearance. The presence of albumin in these tumors, lacking characteristic hepatocellular phenotype, is a potential determinant of hepatic lineage. We conclude that in situ hybridization for albumin mRNA in mice is a useful tool in the differential diagnosis of hepatocellular carcinoma, particularly in the case of pulmonary metastasis. This technique may also enable recognition of hepatocyte differentiation in glandular structures with phenotypic features of biliary cells, as seen in mixed hepatocellular-cholangial neoplasms.

Coxsackievirus-induced chronic myocarditis in murine models.

Challenge of several murine strains with two highly myocarditic variants of coxsackievirus B3 (CVB3) induced acute and chronic myocarditis, detectable at 21 and 45 days post-inoculation (p.i.). In-situ hybridization of coronal heart sections showing chronic inflammation with a radiolabelled CVB3 probe detected viral genomic RNA at day 7 p.i. but rarely at 21 or 45 days p.i., suggesting few murine heart cells actively replicate virus during chronic myocardial inflammation. Data will be presented that favour an alternative hypothesis, i.e. autoimmune responses to shared epitopes among CVB3 proteins, cardiac myosin and myocardial cell surface proteins (molecular mimicry) can affect the severity of chronic inflammation. Mice inoculated with human cardiac myosin (HM) prior to a CVB3m challenge develop less myocarditis than mice inoculated with virus only, suggesting that antibodies stimulated by HM bind virus, reduce the virus burden and provide protection. Mice inoculated with HM only develop non-neutralizing antibodies against purified CVB3m particles. Several strains of mice inoculated with specific synthetic peptides of HM produce antibodies against CVB3m and/or develop cardiomyopathy. Thus antigen-challenged mice can produce antibodies which cross-react among CVB3m HM or cardiac cells to protect or exacerbate heart disease.

Molecular mimicry, anti-coxsackievirus B3 neutralizing monoclonal antibodies, and myocarditis.

Molecular mimicry has been suggested as one mechanism to explain chronic myocarditis in some murine strains in the postinfectious period following induction of acute myocarditis by coxsackievirus B3 (CVB3). To test this hypothesis, neutralizing mAbs were generated against a highly myocarditic CVB3 virus (CVB3m). These mAbs neutralized several myocarditic and amyocarditic CVB3 variants by cytopathic effects inhibition assays. Data from several experiments suggest that these mAbs recognize discontinuous epitopes on CVB3m capsid proteins. Several mAbs were found to induce cardiopathologic alterations subsequent to i.p. inoculation of normal adolescent male CD-1 or C3H/HeJ mice. Immunocytochemical assays demonstrated significant binding of two mAbs to the surface of normal cultured murine cardiac fibroblasts. Also, several mAbs were shown to participate in C-mediated lysis of normal cardiac fibroblasts, but this property did not correlate well with cardiopathogenic potential. The two properties of a mAb that were the best predictors for cardiopathogenic potential were the capacity for stimulation of normal murine fibroblasts to produce a chemoattractant activity for unelicted murine peritoneal macrophages, and the capacity for recognition of an epitopes(s) on murine or human cardiac myosins. These data show that some anti-CVB3m neutralizing mAbs can participate in proinflammatory reactions in vitro and induce cardiopathologic alterations in vivo, suggesting one mechanism by which CVB3-induced chronic inflammation in murine heart tissues can be sustained in the absence of continued virus replication.

Space optics: an introduction by the editors.

This feature of Applied Optics consists of papers on the Hubble Space Telescope and its instruments as well as other new instruments and other new optics technology for space science. Many of the papers are an outgrowth of the papers presented at the Second Space Optics Topical Meeting, October 1991, in Williamsburg, Va. This introduction provides an overview for the papers related to the Hubble Space Telescope: measurement of the error and approaches to correct for the error.

Optical design of zero-power Hubble Space Telescope wave-front correctors for null testing.

The optical design of the second-generation wide-field/planetary-camera instrument for the Hubble Space Telescope has been modified to compensate for the spherical aberration of the optical telescope assembly (OTA) by introduction of undercorrected spherical aberration into the wave front. This instrument can be tested in a simple manner to ensure that its aberration contribution has the proper sign and magnitude. We present designs for a near-zero power doublet lens that can be used to generate a spherically aberrated wave front that is similar to the OTA wave front. When this lens is used in combination with the instrument, a near-perfect or nulled wave front should be produced, resulting in a high-quality point image on axis. We also present lens designs for a similar test that can be performed on the OTA simulators now being built to verify the other second-generation instruments.

Telescope simulators for Hubble: an overview of optical designs.

Various optical configurations for Hubble Space Telescope simulators have been proposed, and some are being built for use as verification tools to characterize the performance of second-generation instruments during ground testing. We describe the Hubble Space Telescope, present an overview of three optical designs for simulators, and discuss the relative advantages and disadvantages of each configuration.