Immunosuppression with cis-Platinum (II) Diammino-dichloride: Effect on Antibody Plaque-Forming Spleen Cells

A new antitumor compound, cis-platinum (II) diamminodichloride, suppressed antibody plaque-forming cells in C(3)H mice when given in a single dose of 10 mg per kg of body weight within 2 days before or after sensitization.     

Analysis of genetic heterogeneity of hepatitis C viruses in Central America reveals a novel genetic lineage

Hepatitis C virus (HCV) has high genomic variability and at least six different types have been reported. The genotypes distribution is currently unknown among HCV strains circulating in Central America. In order to study the degree of genetic variability of strains isolated in Costa Rica, sequence data obtained from the 5' non coding region from 7 patients from Costa Rica were compared with published sequences from 57 strains of all types. The phylogenetic analysis revealed the existence of type 1 strains of a novel genetic lineage, recently described for some South American countries, and indicates an increasing diversification of HCV.     

Regulation of the immune response: II. Further studies on differences in ability of F(ab′)2 and 7S antibodies to inhibit an antibody response

The ability of F(ab′)₂ antibody preparations to suppress an immune response is much less than that of intact 7S antibody. The activity possessed by F(ab′)₂ preparations withstood repurification procedures, hence contamination with intact 7S antibody is unlikely. Daily or thrice daily injections of antibody did not make equal the suppressive activities of F(ab′)₂ and intact antibody, indicating that rapid excretion of F(ab′)₂ antibody is not the sole factor involved in the difference in immunosuppressive potency between intact 7S and F(ab′)₂ antibody. Some possibilities for distinct differences in the mechanism of the immuno-suppressive action of F(ab′)₂ and 7S antibodies are raised and discussed.     

A mixture of ammonium perchlorate and sodium chlorate enhances alterations of the pituitary-thyroid axis caused by the individual chemicals in adult male F344 rats

Ammonium perchlorate (AP) and sodium chlorate (SC) have been detected in public drinking water supplies in many parts of the United States. These chemicals cause perturbations in pituitary-thyroid homeostasis in animals by competitively inhibiting iodide uptake, thus hindering the synthesis of thyroglobulin and reducing circulating T(4) (thyroxine). Little is known about the short-term exposure effects of mixtures of perchlorate and chlorate. The present study investigated the potential for the response to a mixture of these chemicals on the pituitary-thyroid axis in rats to be greater than that induced by the individual chemicals. Adult male F-344 rats were exposed, via their drinking water, to the nominal concentrations of 0.1, 1.0, 10 mg/L AP or 10, 100, 1000 mg/L SC and their mixtures for 7 days. Serum T(4) levels were significantly (p < 0.05) reduced in rats following exposure to the mixtures, but not after exposure to the individual chemicals. Serum T(3) (triiodothyronine) was not altered by treatment and TSH (thyroid stimulating hormone) was only increased after the high-dose chlorate treatment. Histological examination of the thyroid gland showed colloid depletion and hypertrophy of follicular epithelial cells in high-dose single chemical and all mixture-treated rats, while hyperplasia was observed only in some of the rats treated with mixtures (AP 10 + SC 100, AP 0.1 + SC 1000, and AP 10 + SC 1000 mg/L). These data suggest that short-term exposure to the mixture of AP and SC enhances the effect of either chemical alone on the pituitary-thyroid axis in rats.     

Effect of hemoglobin concentration variation on the accuracy and precision of glucose analysis using tissue modulated, noninvasive, in vivo Raman spectroscopy of human blood: a small clinical study

Tissue modulated Raman spectroscopy was used noninvasively to measure blood glucose concentration in people with type I and type II diabetes with HemoCue fingerstick measurements being used as reference. Including all of the 49 measurements, a Clarke error grid analysis of the noninvasive measurements showed that 72% were A range, i.e., clinically accurate, 20% were B range, i.e., clinically benign, with the remaining 8% of measurements being essentially erroneous, i.e., C, D, or E range. Rejection of 11 outliers gave a correlation coefficient of 0.80, a standard deviation of 22 mg/dL with p<0.0001 for N=38 and places all but one of the measurements in the A and B ranges. The distribution of deviations of the noninvasive glucose measurements from the fingerstick glucose measurements is consistent with the suggestion that there are at least two systematic components in addition to the random noise associated with shot noise, charge coupled device spiking, and human factors. One component is consistent with the known variation of fingerstick glucose concentration measurements from laboratory reference measurements made using plasma or whole blood. A weak but significant correlation between the deviations of noninvasive measurements from fingerstick glucose measurements and the test subject's hemoglobin concentration was also observed.     

C3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria

The immunogenicity of recombinant protein or anti-viral DNA vaccines can be significantly improved by the addition of tandem copies of the complement fragment C3d. We sought to determine if the efficacy of a circumsporozoite protein (CSP)-based DNA vaccine delivered to mouse skin by gene gun was improved by using this strategy. Instead, we found that C3d suppressed the protective immunity against Plasmodium berghei malaria infection and deviated immunity, most notably by suppressing the induction of antibodies specific for the CSP C-terminal flanking sequence and by suppressing the induction of CSP-specific IL-4-producing spleen cells. We further showed that C3d bound to the C-terminal flanking sequence of the CSP, which may explain the immune deviation observed in CS/C3d chimeric antigen. We have thus identified C3d-mediated epitope masking and shifting of both the humoral and cellular immune responses as a potential novel escape mechanism, which plasmodia may use to divert the induction of protective immunity.     

Genotyping of Toxoplasma gondii strains from immunocompromised patients reveals high prevalence of type I strains

Toxoplasma gondii is an important food- and waterborne opportunistic pathogen that causes severe disease in immunocompromised patients. T. gondii has an unusual clonal population structure consisting of three widespread lineages known as I, II, and III. To establish the genotypes of strains of T. gondii associated with human toxoplasmosis, we have developed a set of four highly sensitive and polymorphic nested PCR markers. Multiplex nested PCR analysis was used to genotype parasites in cerebral spinal fluid samples from 8 of 10 human immunodeficiency virus-positive patients. Remarkably, a majority of these patients had infections with type I strains or strains containing type I alleles, despite the fact that this lineage is normally uncommon in humans and animals. Multiplex analysis of these four unlinked makers was able to distinguish all three common genotypes and also detected two strains with mixed genotypes. Further analysis based on sequencing of a polymorphic intron revealed that one of these recombinant strains was an exotic lineage distinct from the archetypal clonal lineages. The multiplex nested PCR analysis described here will be useful for analyzing the contribution of parasite genotype to toxoplasmosis.