Immunologic and pharmacologic concepts of monoclonal antibodies

While monoclonal antibodies have solved many of the difficulties of using immunologic reagents for radioimmunodiagnosis and therapy, in the 13 years since their introduction a number of persistent problems remain, most notably a low yield of antibody-producing cells from the fusion process, difficulty in obtaining high-affinity antibodies, and the potential immunogenicity of murine immunoglobulins (Igs). Several solutions are under development, including fusion techniques that enrich for cells producing desired antibodies, production of human-mouse chimeric antibodies by recombinant DNA technology, and the generation of human monoclonal antibodies by promising new approaches. Until these upcoming methodologies are established, and to better direct their development and application, a sound understanding of the pharmacology of presently available native and modified monoclonal antibodies is crucial. Although much has been already determined in this area, a great deal of further clarification remains necessary.     

Administration of kainic acid and colchicine alters mu and lambda opiate binding in rat hippocampus

Quantitative in vitro autoradiography was used to assess the effects of kainic acid (KA) and colchicine (COL) on mu and lambda opiate binding in the rat hippocampus. Rats were treated with either systemic KA, a neurotoxin that damages CA3 pyramidal cells and causes seizures and wet-dog shakes, or intrahippocampal COL to destroy dentate granule cells and their mossy fibers, or both toxins. Moderate levels of mu binding were detected in the pyramidal layer and in the stratum lacunosum-moleculare; binding was greater in the ventral hippocampus. Levels of mu binding were markedly increased in all regions 48 h after treatment with KA. Two weeks after COL treatment, there was a modest decrease in mu binding; COL plus KA gave results similar to COL alone. Dense lambda binding was present over the mossy fibers in the stratum lucidum, but was absent over the pyramidal layer. In contrast to mu binding, lambda binding was greater in the dorsal hippocampus. KA alone had little effect on lambda binding, whereas COL alone caused large decreases. KA plus COL caused even larger decreases in lambda binding, to as much as 85% below control. These results demonstrate that mu and lambda binding are localized to different parts of the hippocampus, respond differently to neurotoxin lesions, and likely serve different roles in this brain region. The number of mu sites is responsive to the release of enkephalin; these receptors appear to be linked to opiate-induced hippocampal seizure activity, especially wet-dog shakes. Lambda sites may serve as autoreceptors on mossy fibers.     

Cranial nasal bone grafts

Reconstitution of the nasal scaffolding with maintainence of soft tissue proportions either following severe facial trauma or as a sequela to aesthetic rhinoplasty misadventures frequently is best achieved using the stability afforded by bone grafts. Split cranial bone grafts offer many advantages and may be the donor site of choice, and may even allow such surgery to be performed on an outpatient basis in some cases. The use of miniplate or screw osteosynthesis, now commonly accepted as a superior technique in craniomaxillofacial procedures, may simplify fixation of these calvarial nasal bone grafts with an apparent decrease in the risk of resorption.     

Hypothermia protects brain function in acute carbon monoxide poisoning

The role of body temperature in the morbidity and mortality resulting from acute severe carbon monoxide (CO) poisoning (2400 ppm CO, 90 min) was investigated using an unanesthetized animal model. Modified Levine prepared female rats (left common carotid artery and jugular cannulated) displayed a lower rate of recovery period (4 hr) re-warming, and an increased mortality rate and behaviorally-assessed neurologic index (NI) compared to normal rats. This indicated their greater susceptibility to CO hypoxia, although the degree of CO-induced hypothermia was the same in both groups. The whole-body cooling of Levine rats to a similar extent prior to CO exposure increased somewhat the post-CO re-warming rate, and marginally decreased NI and mortality during CO exposure (in-CO). In contrast, maintenance of constant body temperature by external heating during CO exposure resulted in a negative post-CO re-warming rate and sharply increased NI and in-CO mortality. Normal euthermic rats were much less severely affected by CO. The results suggest that hypothermia, whether CO-induced or produced by prior cooling, provides measurable protection of brain function during acute severe CO poisoning, and that maintenance of body temperature increases in-CO mortality and interferes with ability to thermoregulate and increases NI in survivors.     

Effect of iron and liver injury on the pathogenesis of Vibrio vulnificus

Noncholera vibrio species can cause necrotizing soft tissue infections and cellulitis in addition to gastroenteritis. Cellulitis and necrotizing soft tissue infections frequently occur in people with liver disease or in people who are in some way a compromised host. We studied the effect of Vibrio vulnificus on the mortality of mice treated with carbon tetrachloride, an agent that causes liver damage, Desferal, an iron-chelating agent, or iron. The LD50 of V. vulnificus is approximately 2.5 X 10(6) CFU. In mice, desferal lowered the LD50 to less than 100 CFU, and carbon tetrachloride lowered the LD50 to approximately 1000 CFU. Twenty percent of the mice that survived had necrosis of the skin overlying the injection site. These studies demonstrate that liver damage and iron chelating agents increase mortality and necrotizing soft tissue infections caused by V. vulnificus.     

Water, trachoma and conjunctivitis.

The incidence of eye infections in a community is generally accepted as an indicator of the adequacy of water supply for their needs. However, discrepancies in the published results from various studies seem to challenge this view. We have reanalysed the published data on trachoma in relation to the most relevant indicators of water accessibility, using prevalence ratios as the single parameter for risk assessment. A definite trend emerges from this review: the incidence of infectious conjunctivitis is not sensitive to differences in water accessibility; on the other hand, a reduction in the risk of trachoma is consistently associated with better access to water. This conclusion may support the efforts of WHO and other multilateral and bilateral agencies to sustain the commitment towards the water supply sector beyond the International Drinking Water Supply and Sanitation Decade.     

Functional characteristics of intraepithelial lymphocytes from mouse small intestine. III. Inability of intraepithelial lymphocytes to induce a systemic graft-versus-host reaction is because of failure to migrate in vivo.

In this study we have investigated whether addition of bone marrow accessory cells or concurrent administration of recombinant IL-2 would allow intraepithelial lymphocytes (IEL) to induce a systemic, lethal GvHR in irradiated hosts. In addition we have studied the ability of IEL to migrate into lymphoid tissues after intravenous injection and compared this with their locomotor capacity in vitro.