Incomplete antigenic cross-reactivity between platelets and megakaryocytes: relevance to ITP

Immune thrombocytopenias are usually associated with normal or increased numbers of megakaryocytes in the marrow. Therefore, the mechanism(s) responsible for the destruction of circulating platelets may not affect megakaryocytes in the same way. One of the possibilities which could account for the differential effect on the cells would be the development of antibodies to components of platelet membranes which are not exposed on the surface of all megakaryocytes. To investigate this possibility, a rabbit antiserum specific for mouse platelets was tested against fresh and cultured mouse megakaryocytes by indirect immunofluorescence. This antiserum cross-reacted with 46% of fresh murine megakaryocytes and 54% of cultured megakaryocytes. Phase- contrast microscopy revealed the reacting megakaryocytes to be fully granulated with irregular contours and in the process of releasing platelets. Nonreactive megakaryocytes demonstrated smooth contours and lacked morphological evidence of thrombocytopoiesis. Electron microscopy showed that only in megakaryocytes (MK) with an irregular contour had the demarcation membrane system (DMS) reached continuity with the plasma membrane. Ultrastructural analysis of megakaryocytes from patients with ITP showed approximately 25% to 50% of megakaryocytes without evidence of injury, whereas 50% to 75% had extensive damage. In undamaged cells, platelet territories had not yet reached the peripheral zone. The DMS of damaged megakaryocytes opened to the exterior elaborating platelets. The observations suggested that some platelet antibodies react only with megakaryocytes which have reached the stage of thrombocytopoiesis. Relevant target antigens may not be exposed on all megakaryocytes before cytoplasmic fragmentation occurs.     

Improved vessel dilator for percutaneous catheterization

Three commercial vessel dilators and a dilator of an improved design were tested during percutaneous catheterization in 16 mongrel dogs to evaluate arterial damage produced with their use. The results indicate that, although all dilators often produce arterial damage, the improved design produced much less damage. In addition, lesions were less severe overall. The dilator has been safely and successfully used in patients for percutaneous vessel catheterization for the past 30 years at the authors' institution.     

Increased height in diabetes mellitus corresponds to the predicted and the adult height

This study was conducted to analyse the effect of childhood-onset diabetes mellitus on adult height. The height at time of diagnosis of 35 children with insulin-dependent diabetes mellitus (IDDM) was compared with growth reference data. Predictions of the adult height were made at the time of diagnosis using the target height and the Tanner-Whitehouse II method. The adult height was compared with both the predicted values and the height of healthy adults. The height at time of diagnosis of the prepubertal children was increased compared with growth reference data, in contrast to pubertal children who had normal heights. Only the prepubertal boys were taller at time of diagnosis. The adult height of the prepubertal patients was taller than growth reference data. The mean adult height in all patients did not differ significantly from the predicted heights. In conclusion, the increased height at the start of IDDM in prepubertal children persists until adulthood.     

Effects of short-term hypoxia on platelet counts of mice

Recent studies have shown that long-term hypoxia causes decreased platelet counts in mice and short-term hypoxia increased platelet counts. In an attempt to explain the mechanism that increases platelet counts of mice after exposure to short-term hypoxia, we measured platelet counts, total circulating platelet counts (TCPC), total circulating platelet masses (TCPM), percentages of 35S incorporation, and platelet sizes. Platelet counts, as well as TCPC and TCPM of mice, increased after 1-3 days of hypoxia, but these values were decreased after 6-7 days of hypoxia. Although platelet counts were increased in hypoxic mice, the percentage 35S incorporation into platelets and platelet sizes did not show a concurrent increase. After 6 days of hypoxia, average platelet diameters began to increase as platelet counts decreased. Splenic release did not account for the increase in platelet counts of mice after short-term hypoxia. It seems possible, therefore, that megakaryocytes "shed" platelets into the circulation in response to hypoxia. The platelets that enter the circulation in response to short-term hypoxia are smaller and incorporate less 35S than platelets that are produced in response to acute thrombocytopenia.     

A field study on the effects of Fort Morgan virus, an arbovirus transmitted by swallow bugs, on the reproductive success of cliff swallows and symbiotic house sparrows in Morgan County, Colorado, 1976

We studied the transmission of Fort Morgan (FM) virus within colonies of nesting Cliff Swallows and House Sparrows under three bridges in Morgan County, Colorado during 1976. Nests were examined, and blood or brain specimens were collected from nestlings once or twice a week. Flying birds and small mammals were also studied. We analyzed nesting activity, virus isolations from nestlings of both species, fledging success, multiple infections within a brood of nestlings, infection frequency by age of nestlings, nestling mortality, and infection frequencies by avian species and bridge site. Fort Morgan virus was isolated from 7% (80/1, 156) of the blood and brain samples collected from nestlings. The duration of viremia for nestling House Sparrows was at least 3-4 days based on virus isolation from sequential blood samples. Viremia of nestling Cliff Swallows and House Sparrows did not reduce fledging success, nor were young nestling sparrows viremic more frequently than older nestling sparrows. Nest destruction (by falling down) was a more important cause of nestling mortality than FM virus infection. All age groups of nestling sparrows were viremic at equal rates, but younger nestlings (less than or equal to 7 days old) were more likely than older nestlings (greater than 7 days old) to develop an encephalitic infection. Among nestling House Sparrows, FM virus infections were clustered in time and space. Nestling House Sparrows with FM virus-infected nest-mates were infected more often than conspecifics whose nest-mates were not infected. We concluded that nestling Cliff Swallows and symbiotic House Sparrows that reside in swallow nesting colonies are the principal vertebrate hosts for the maintenance and amplification of FM virus.     

Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial

The growth fraction of tumors from patients with non-Hodgkin's lymphomas (NHL) has been shown to correlate with survival in retrospective studies. The growth fraction can be evaluated using immunohistochemical techniques employing the Ki-67 monoclonal antibody (MoAb) that marks a nuclear protein present in cycling cells. The purpose of this study was to evaluate the clinical utility of the Ki-67 MoAb for predicting survival. Using a prospective trial design in a multi-institutional cooperative trials group, the proliferative index, clinical outcome, and statistical correlations were independently assessed for previously untreated patients with advanced stages of intermediate- and high-grade histologies of NHL treated on Southwest Oncology Group study (SWOG 8516, Intergroup 0067). The proportion of Ki- 67-positive cells was determined on snap-frozen thin tissue sections. A proliferative index of 80% or greater, as determined from prior retrospective studies, identified a group of patients (18%) who had a poor outcome. Overall survival was significantly reduced in these patients with a high Ki-67-associated proliferative index compared with those with a low proliferative index (P = .001). One-year survival estimates were 82% (low proliferative index) versus 18% (high proliferative index). A multivariate regression analysis incorporating commonly used clinical prognostic features confirmed the independent effect of proliferation on survival (relative risk estimate 5.9; 95% confidence interval, 2.2, 16.1). The Ki-67 MoAb identifies a group of patients with rapidly fatal NHL for whom currently available chemotherapy is inadequate.     

Effect of human gamma interferon on yellow fever virus infection

We studied yellow fever virus infection in two species of monkey: Saimiri sciureus (squirrel monkeys) and Macaca mulatta (rhesus monkeys). Human gamma interferon was administered intravenously in five equal doses, one was given 24 hr before infection followed by four doses 24 hr apart. Interferon reduced the levels and duration of viremia and the severity of hepatitis in squirrel monkeys. Interferon prolonged survival time and delayed the appearance of viremia and hepatitis in infected rhesus monkeys, but it did not change overall mortality.     

Human infections with Tensaw virus in south Florida: evidence that Tensaw virus subtypes stimulate the production of antibodies reactive with closely related Bunyamwera serogroup viruses

Maguari virus, a member of the Bunyamwera serogroup (family Bunyaviridae, genus Bunyavirus) has not been isolated north of Trinidad. Anecdotal information from other investigators has indicated the presence of antibody to Maguari virus in human residents of south Florida. We attributed such antibody to either cross-reactivity with Tensaw virus, the only Bunyamwera serogroup virus known in south Florida, or to cross-reactivity to an antigenic subtype or variant of Tensaw virus. Five strains, identified as Tensaw virus when they were isolated from mosquitoes collected in south Florida more than 20 years ago, were retrieved from storage. They were compared by serum dilution-plaque reduction neutralization tests with Bunyamwera serogroup prototypes Tensaw, Maguari, Cache Valley, and Tlacotalpan viruses. The south Florida isolates were shown to be most closely related to prototype Tensaw virus and most distantly related to prototype Maguari virus. One isolate could not be distinguished from prototype Tensaw virus, and the other 4 appeared to be subtypes of prototype Tensaw virus. More than 300 serum samples from humans in south Florida were tested for neutralizing antibody to prototypes Tensaw and Maguari viruses and to 3 of the field isolates. Thirteen had antibody to prototype Tensaw virus only, 19 to prototype Maguari virus only, and 39 to both. Antibody to all but 6 of these 71 was attributed to infection with Tensaw virus, to a subtype of Tensaw virus, or to travel or birth outside the United States. It is likely that those with antibody to Maguari virus only had been infected with yet another subtype of Tensaw virus, although another, undiscovered, Bunyamwera serogroup virus may exist in south Florida.