Expanded safety and immunogenicity of a bivalent, oral, attenuated cholera vaccine, CVD 103-HgR plus CVD 111, in United States military personnel stationed in Panama

To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. A total of 170 partially-immune American soldiers stationed in Panama received one of the following five formulations: (a) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(7) CFU, (b) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(6) CFU, (c) CVD 103-HgR alone at 10(8) CFU, (d) CVD 111 alone at 10(7) CFU, or (e) inactivated Escherichia coli placebo. Among those who received CVD 111 at the high or low dose either alone or in combination with CVD 103-HgR, 8 of 103 had diarrhea, defined as three or more liquid stools. None of the 32 volunteers who received CVD 103-HgR alone or the 35 placebo recipients had diarrhea. CVD 111 was detected in the stools of 46% of the 103 volunteers who received it. About 65% of all persons who received CVD 103-HgR either alone or in combination had a fourfold rise in Inaba vibriocidal titers. The postvaccination geometric mean titers were comparable among groups, ranging from 450 to 550. Ogawa vibriocidal titers were about twice as high in persons who received CVD 111 as in those who received CVD 103-HgR alone (600 versus 300). The addition of CVD 111 improved the overall seroconversion rate and doubled the serum Ogawa vibriocidal titers, suggesting that the combination of an El Tor and a classical cholera strain is desirable. While CVD 111 was previously found to be well tolerated in semiimmune Peruvians, the adverse effects observed in this study indicate that this strain requires further attenuation before it can be safely used in nonimmune populations.     

Clonal heterogeneity of HLA-B27 cellular allorecognition. Delineation of immunodominant sites

The fine specificity of nine cytolytic T lymphocyte (CTL) clones obtained after stimulation of HLA-B27- responder lymphocytes with B27.1+ lymphoblastoid cell lines has been analyzed. These clones defined three different reaction patterns when tested against a panel of target cells including those expressing all known HLA-B27 subtypes: (a) specific recognition of HLA-B27.1, B27.2 and B27d, (b) selective reactivity with B27.1, B27d and HLA-B40 and (c) selective recognition of B27.1, B27.2, B27d, B27f and B40. Representative clones within each group were analyzed in detail. Differences in lytic ability of the various susceptible targets within each group were established by cold target inhibition analyses and by blocking experiments with anti-CD3 and anti-CD8 monoclonal antibodies. When correlated with the known structure of the HLA-B27 subtypes, these results demonstrate the critical relevance of amino acid changes within residues 77-81 and at position 152 in modulating allospecific CTL recognition of HLA-B27.1 and suggest that these residues could be involved in the structure of immunodominant regions of this antigen. The observed cross-reactions with HLA-B40, differing from B27.1 in 16 amino acid residues, suggest that the simultaneous occurrence of multiple amino acid changes could have mutually compensatory effects, so that a cross-reactive epitope might result from various combinations of polymorphic residues.     

Defibrination of blood plasma for use in serological tests for syphilis

Syphilitic plasma can be salvaged from discarded blood donations and converted to serum by defibrination. Sixty-nine units of plasma were treated with a stock solution of 100 U of thrombin per ml in 1 M calcium chloride and then with a 10% (wt/vol) solution of kaolin. Fibrinogen concentrations detected in initial plasma samples ranged from 94 to 4970 mg/liter (mean, 2532 mg/liter) for samples that were reactive by the rapid plasma reagin circle card test (RPR) and from 314 to 2742 mg/liter (mean 1528 mg/liter) for samples that were not reactive by the RPR. The treated samples showed no measurable fibrinogen remaining after the defibrination process. In the nontreponemal RPR for syphilis, 86% of the treated plasma samples retained the same endpoint titer as that of the initial plasma sample. When the Treponema pallidum passive-particle-agglutination test was used, 98% retained the same reactivity. In the Captia Syphilis-G enzyme immunoassay, 89% of the treated samples demonstrated no change in reactivity index, and in the fluorescent treponemal antibody absorption test, 96% showed no reduction in fluorescence. Human sera containing antibodies to syphilis are used at the Centers for Disease Control and Prevention for the preparation of reference controls or as samples for proficiency testing. Finding reactive sera is becoming more difficult due to the general decline of syphilis cases in the United States. The decreasing availability of these sera can be alleviated by salvaging plasma and converting it to serum.     

Prenatal haloperidol treatment decreases nerve growth factor receptor and mRNA in neonate rat forebrain.

Pregnant rats were treated daily with haloperidol (2 mg/kg) for 11 days until 1 day before birth. The levels of nerve growth factor (NGF), its receptor (NGFR) and NGFR-mRNA were measured in forebrain of 2-day old postnatal rats. Using Northern blot analysis, we observed a decrease in NGFR-mRNA. Furthermore, in binding studies, Kd and Bmax of treated rats were lower than in controls, but only in the low affinity binding sites. However NGF and its mRNA did not change after haloperidol treatment. In conclusion, our results suggest that prenatal haloperidol treatment can modify the development of forebrain cells, by changing NGFR expression.     

Exercise and brain catecholamine relationships with brown adipose tissue and whole-body oxygen consumption in rats

Brown Adipose Tissue (BAT) is thought to maintain caloric homeostasis by increasing its metabolic rate during periods of energy surfeit or low environmental temperatures and decreasing it during periods of deprivation or high environmental temperatures. The present study investigated the relationship of BAT and whole-body metabolic rate with negative energy balance induced by a minimally stressful exercise regimen. Twenty-four rats exercised in a running wheel for 2 hours per day for 8 weeks for food reinforcement either under a variable ratio or variable time schedule. Whole-body oxygen consumption and the thermic effect of a test meal were then measured, the rats sacrificed, BAT weight and oxygen consumption measured, and the brains assayed for catecholamines. Food intake was found to be positively correlated with expenditure either in the form of exercise, overnight weight loss, or BAT metabolic rate. Brain dopamine concentrations were found to be related to BAT metabolic rate which was in turn related to the amount of weight lost overnight and the amount of food intake. Running was positively correlated with BAT metabolic rate, suggesting that brown adipose tissue is not simply an organ of caloric homeostasis or thermoregulation. BAT, then, appears to be a multi-purpose tool used by a number of systems which regulate body temperature and energy metabolism.     

Evolution of MHC-G in humans and primates based on three new 3'UT polymorphisms

MHC-G is a class Ib (non-classical) major histocompatibility complex (MHC) whose functional and evolutionary characteristics are still under scrutiny. The study of noncoding sequences in the MHC genes may provide important phylogenetic information. In this work we have sequenced the MHC-G exon 8, which encodes for the 3'UT region, in different species of primates. It has been shown that: (1) a previously described 14 base pair (bp) deletion polymorphism is human-specific and the HLA-G alleles may be classified according to its absence or presence; (2) another newly described 3 bp deletion/insertion polymorphism is also human-specific; and (3) another newly described 51 bp deletion polymorphism is common to Pongidae and humans, but is not found in other primates belonging to the Cercopithecinae family. A hypothesis on the evolutionary pathway of this gene is put forward in the light of these findings.     

Respiratory mechanics and pleural remodelling in pleurodesis induced by barium sulphate

The aim of this study was to determine whether an intrapleural injection of barium sulphate would produce pleurodesis in rats. Additionally, respiratory mechanics and pleural remodelling were analysed. Single intrapleural injection of barium sulphate (100%) or saline was given to Wistar rats. Respiratory system, lung, and chest wall elastic, resistive and viscoelastic/inhomogeneous pressures were measured by the end-inflation occlusion method at 2 and 30 days after injection. The pleura were examined for gross and histopathological evidence of pleural inflammation and fibrosis, and the underlying lungs were also studied by morphometry. All pulmonary mechanical parameters increased at day 2, but were not different from control at 30 days after injection. Chest wall mechanical parameters did not change. Macroscopic evaluation demonstrated pleural adherence without haemothorax. Histopathologic analysis showed pleural inflammation and fibrosis. There was no alveolar inflammation or fibrosis in both groups. In conclusion, barium sulphate induced pleurodesis with either no changes in respiratory mechanics or lung lesion at day 30.     

Shashi XLMR syndrome: report of a second family

This report describes a family with mental retardation in two brothers. The pedigree is consistent with either X-linked mental retardation or autosomal recessive inheritance. The clinical features consist of coarse face, prominent lower lip, large testes, and obesity. This same constellation of findings was observed in a family with X-linked mental retardation (XLMR) reported by Shashi et al. [2000: Am J Hum Genet 66:469-479]. Furthermore, haplotype analysis was consistent with localization of the Shashi XLMR syndrome in Xq26-q27. Thus, the family likely represents a second occurrence of the Shashi XLMR syndrome.     

Limb preference after unilateral pyramidotomy in adult and neonatal rats

As previously reported, unilateral pyramidotomy in newborn rats results in the development of an aberrant ipsilateral corticospinal tract that originates from the intact side. In the present study, limb preference after unilateral pyramidotomy in adult and neonatal rats was examined in search of differences that might correlate with this aberrant tract. However, no significant differences were observed between the two groups. Postoperatively, adult animals preferred the limb corresponding to the intact corticospinal tract in spite of a pre- and postoperative testing bias toward the opposite limb. Similarly, the animals that sustained neonatal lesion followed by testing at maturity also preferred the limb corresponding to the normal crossed corticospinal tract.