Antibodies against the extracellular enveloped virus B5R protein are mainly responsible for the EEV neutralizing capacity of vaccinia immune globulin

In the event of smallpox bioterrorism, widespread vaccination may be required. Vaccinia immune globulin (VIG) has been used to treat complications from the smallpox vaccine. While the potency of VIG was defined by its ability to neutralize intracellular mature virus, a second form of vaccinia called the extracellular enveloped virus (EEV) is critical for virus spread in the host. The B5R-protein is one of many EEV-specific proteins. Immunoprecipitation and ELISA revealed that VIG recognizes the B5R-protein. An EEV plaque-reduction assay using a recombinant vaccinia that lacks the majority of the extracellular domain of B5R showed that the ability of VIG to neutralize EEV is principally directed at B5R. In addition, absorbing out the anti-B5R antibody present in VIG through the addition of recombinant B5R protein abrogated VIG's ability to significantly neutralize wild-type EEV. This work demonstrates the prominent role of B5R as a target of EEV-neutralizing activity of human antibodies.     

Substance P-immunoreactive nerves in the rat kidney

Previously published data have indicated that in the rat, unlike other species examined, the kidney is not supplied by sensory nerves containing substance P (SP). As part of a study of reflex control of renal function in the rat, we have now reassessed this situation. Many fine, varicose, SP-immunoreactive nerve fibers were found in the wall of the proximal ureter and the renal pelvis, and around the larger renal blood vessels. Sparser populations of similar nerves were also seen running close to proximal and distal tubules in the renal cortex. Occasional fibers were seen at the margins of the glomeruli. Our findings suggest that sensory nerves containing SP may carry sensory information of several types from the rat kidney.     

Different patterns of immunolocalization of calcitonin gene-related peptide and substance P in sympathetic ganglia of normotensive and genetically hypertensive rats

Calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity were investigated in the superior cervical ganglion of normotensive and genetically hypertensive Otago Wistar rats by an immunoperoxidase method. CGRP- and SP-positive varicose axons invested separate subpopulations of ganglion cells, neither of which contained neuropeptide Y. The densities of CGRP axons were similar in normotensive and hypertensive rats while the numbers of SP axons were several times higher in the hypertensive strain. Decentralization of the ganglion or chronic capsaicin treatment removed all immunoreactive terminals, indicating that both axon populations are likely to be collaterals from thoracic sensory afferents.     

Cost effectiveness of vaccination against pneumococcal pneumonia

We used cost-effectiveness analysis to examine the medical-care costs of vaccination against pneumococcal pneumonia in relation to its effects on health. Vaccination could add a year of healthy life among all age groups for about $4,800 in net medical-care costs. Cost-effectiveness ratios vary according to the age of the person vaccinated--from $1,000 per year of healthy life for an adult 65 years old or older to $77,000 per year of healthy life for a child between the ages of two and four. These ratios may change substantially with variations in such factors as the cost of vaccination, the duration of immunity, the efficacy and composition of the vaccine, and the percentage of pneumonia that is pneumococcal. This analysis has particular relevance for the Medicare program, since present legislation excludes coverage of most immunizations and other preventive services. Provision of pneumococcal vaccine to the elderly and inclusion of the vaccine as a Medicare benefit merit serious consideration.     

Absence of estimated glomerular pressure autoregulation during interrupted distal delivery.

Micropuncture studies in dogs have suggested that a distal tubule-to-afferent arteriole feedback system may participate in the autoregulation mechanism at the single-nephron level. To evaluate the effect of interrupted distal delivery on glomerular capillary pressure (GP) and its autoregulation, the proximal tubule was blocked with oil and maximal stop-flow pressure was measured with a micropressure servo-null system. The GP was estimated from the sum of stop-flow pressure and the plasma colloid osmotic pressure (membrane oncometer). In 18 dogs given a mild mannitol load, average +/- SD control arterial pressure was 118 +/- 16 mmHg, proximal tubule pressure was 24 +/- 5 mmHg, and estimated GP averaged 70 +/- 10 mmHg. There was a highly significant relationship between estimated GP and arterial blood pressure. Similar results were obtained in hydropenic dogs. In response to decreases in renal arterial pressure in individual dogs, stop-flow pressure and estimated GP failed to exhibit autoregulation although autoregulation of renal blood flow, GFR, and proximal tubule pressure was observed over an arterial pressure range of 150-95 mmHg. These results indicate that interruption of normal distal delivery by proximal tubule blockage interferes with the ability of the nephron to autoregulate glomerular pressure. They provide further evidence in support of the concept that a distal tubular feedback mechanism participates, at least in part, in the autoregulatory control of glomerular pressure.     

Novel translocation of the BCL10 gene in a case of mucosa associated lymphoid tissue lymphoma

Interest has focused on a recently identified gene, BCL10, thought to play an important role in the genesis of extranodal, marginal zone (MALT) lymphomas. This gene belongs to a family containing caspase recruitment domains (CARD), that are involved in the apoptotic pathway. Translocations of the BCL10 gene to the immunoglobulin heavy chain locus at 14q32 have been described. We report herein a case of MALT lymphoma showing t(1; 2)(p22; p12). The translocation was shown to involve the BCL10 gene and the immunoglobulin kappa light chain locus by fluorescence in situ hybridization.     

Pneumotoxicity and thrombocytopenia after single injection of monocrotaline

Adult Sprague-Dawley rats were treated once with 105 mg/kg monocrotaline (MCT) subcutaneously or an equivalent volume of isotonic saline and examined 2, 5, 10, and 14 days later. The earliest changes observed were in the platelet count, which was decreased in the MCT animals at 2, 5, and 10 days postinjection. Clearance of perfused 5-hydroxytryptamine, a function of pulmonary vascular endothelium, was unaltered in isolated lungs of treated rats until 5 days after dosing but decreased progressively thereafter in the MCT animals and was 24% less than controls by 14 days. The magnitude of this effect was dose related. Inflow perfusion pressure was elevated in perfused lungs of MCT-treated animals at day 14. Right heart hypertrophy, measured as an increase in the ratio of right ventricle to left ventricle plus septum weights, was not evident until 14 days after treatment. A larger dose of MCT (130 mg/kg) resulted in significant mortality, whereas a lower dose (60 mg/kg) did not result in right ventricular hypertrophy 2 wk after treatment. The treatment regimen described has advantages over administration of MCT by ingestion and may prove suitable for investigations of the mechanism by which MCT results in pulmonary hypertension.