How important are hemoparasites to migratory songbirds? Evaluating physiological measures and infection status in three neotropical migrants during stopover.

Long-distance migrations are energetically expensive for many animals, including migratory songbirds. During these demanding journeys, birds likely face limitations in allocating resources to different physiological functions, including lipid reserves needed to fuel the migration and costly immune defense against pathogens. We sampled three species of long-distance migratory songbirds during their fall migration through coastal Georgia and quantified their body condition, subcutaneous fat reserves, and infection status with blood parasites (Hemoproteus and Plasmodium). We also quantified cellular immunity, on the basis of total and differential white blood cell counts, and estimated individual stress levels, using the heterophil∶lymphocyte (H∶L) ratio. We tested whether birds infected with blood parasites had decreased fat measures, poorer body condition, or increased stress levels (as reflected by H∶L ratios). We also examined relationships between immune cell profiles and the following variables: body condition, subcutaneous fat, infection status, age, and species. Infected birds did not show greater H∶L ratios, poorer body condition, or lower fat measures, but in one species infected individuals showed significantly elevated leukocyte counts. Although we found little evidence for negative relationships between immune cell counts and body condition or fat measures, as might reflect underlying trade-offs in resource allocation, our results concerning hemoparasites are consistent with past work and suggest that chronic hemoparasite infections might have minimal effects on the outcome of long-distance migratory flight.

Leukocyte response to eastern equine encephalomyelitis virus in a wild passerine bird.

Leukocyte counts are frequently used to assess the immunologic status of animals; however, few studies have directly looked at the predictive value of leukocyte counts and an animal's ability to respond to an infection with a pathogen. Understanding how an animal's leukocyte profile is altered by an active infection can assist with interpretation of leukocyte profiles in animals for which infection status is not known. In this study we examine the leukocyte counts of gray catbirds (Dumetella carolinensis) infected with eastern equine encephalomyelitis virus (EEEV). Blood smears were collected from infected catbirds on -4, 2, 5, and 14 days postinoculation (dpi) with EEEV, and from a corresponding uninfected control group, to monitor leukocyte counts. Although we found that preinfection leukocyte counts were not a reliable predictive of a catbird's viremia, we did find that infected catbirds exhibited significant hematologic changes in response to EEEV infection. We observed a significant drop in all subpopulations of leukocytes (i.e., lymphocytes, monocytes, and granulocytes) following infection. Lymphocytes and granulocytes still had not recovered to preinfection levels at 14 dpi. Uninfected catbirds also exhibited statistically significant changes in leukocyte counts, but this was due to a slight increase at 14 dpi and was not considered biologically relevant. Studies such as this can provide important information for field ecoimmunologists that use leukocyte counts to assess immunocompetence in free-living animals.

Mechanism of technetium 99m sestamibi parathyroid imaging and the possible role of p-glycoprotein.

BACKGROUND: Localization of parathyroid glands is critical in the treatment of recurrent or persistent hyperparathyroidism. Technetium sestamibi imaging may improve localization; however, the mechanism of visualization of parathyroid tissue remains unclear. On the basis of the chemical structure of sestamibi it has been suggested that p-glycoprotein is involved in the transport of sestamibi across cell membranes. This study was designed to examine sestamibi uptake and retention and p-glycoprotein expression in normal and abnormal parathyroid tissue. METHODS: Thirty-two consecutive patients underwent 2-methoxy-isobutyl-isonitrile imaging immediately before parathyroid exploration. Tissue was obtained from normal and abnormal parathyroids and from the thyroid gland. Touch preparations gave rapid confirmation of tissue origin. Specimens were trimmed and weighed, and gamma-emission was counted. Percentage injected dose per gram of tissue was calculated. Immunohistochemistry was obtained with a battery of monoclonal antibodies to identify p-glycoprotein in parathyroid tissue submitted for permanent histologic examination. Slides were graded by a pathologist familiar with immunohistochemistry. RESULTS: Abnormal parathyroid tissue had a higher mean retention of injected dose per gram than did normal thyroid and parathyroid tissue. Immunohistochemistry revealed that abnormal parathyroid tissue expresses less p-glycoprotein. CONCLUSIONS: These results suggest that size is not the single determinant of parathyroid visualization and that p-glycoprotein expression may be involved in the mechanism of parathyroid imaging.

False tumor-positive lymph nodes in radioimmunodiagnosis and radioimmunoguided surgery: etiologic mechanisms.

We investigated the causes of false-positive (nontumor cell) focal uptake in radioimmunodiagnosis (RAID) and false-positive high counts in radioimmunoguided surgery (RIGS). Tissue blocks of two such RAID cases were recut and examined by immunohistochemistry (IH) (group 1). Lymph nodes in the drainage area of 14 colon cancers selected because of tumor-positive draining nodes were examined similarly (group 2). The lymph nodes in group 1 showed nontumor cell germinal center (GC) and rare macrophage (M phi) positivity with monoclonal antibody (mAb) CC49 to tumor antigen (Ag) TAG-72, the same Ag to which the mAb B72.3, used for the RAID studies, was directed. In group 2, CC49 staining was observed in the colon cancers, in noncellular tumor Ag in lymphatic channels, and in the GC of draining nodes in a pattern similar to that of follicular dendritic cells (FDC). An In-111-mAb/tumor Ag (TAG-72 or CEA) complex can result in false-positive RAID/RIGS studies by In-111 retained in the lysosomes of lymph node M phi, following attachment of the mAb to the Ag, and their catabolism in the M phi. An I-125-mAb to either tumor Ag could lead to false positive RIGS studies due to its attachment to the Ag portion of ag/ab complexes affixed to the FDC in the GC of the lymph nodes draining a tumor.

Analysis of monoclonal antibody uptake in tumours.

Power (y = axb) and linear (y = a + bx) equations were derived, relating percentage uptake (y) of radionuclide tagged specific (SP) and non-specific (NSP) monoclonal antibody (MoAb) and blood flow (BF) to tumour weight (x) in animal models in the literature. Power equations were more significant than linear equations, that is, MoAb uptake and blood flow did not increase linearly with tumour weight. The power equations were similar to the equation relating surface area (SA) to the volume (V) of a sphere (SA = 4.84 V0.67), but with some categorical differences, namely aSP greater than aSA greater than aNSP, aBF and bSA greater than bNSP bBF.bSP was variable. These results can be correlated with tumour physiology. a and b for non-specific MoAb uptake were similar to those for blood flow, suggesting antibody uptake is blood-flow related. Tumours are vascularized from their surface, explaining their relationship to surface area. Autoradiographs show that the high aSP values are due to preferential uptake of specific MoAb by tumours.

Intrapatient and interpatient comparison of tumor size and monoclonal antibody uptake in melanoma.

In two panels totaling 52 patients with melanoma who were imaged with In-111 labeled 96.5 or ZME-018 (ZME) monoclonal antibodies (MoAb), four patients demonstrated numerous metastases (greater than or equal to 20) in the subcutaneous tissues and peripheral lymph nodes. These constituted four intrapatient groups of tumors. These were selected for an intrapatient comparison of tumor size and uptake. Data on 16 additional patients imaged with 96.5 MoAb with fewer (less than or equal to 11) such tumor foci were pooled and used as an interpatient control group of tumors. Uptake was graded 0-5+ (liver = 4+). The data were similar in all five groups. All tumors with a diameter less than 0.7 cm were not detected. All large tumors were demonstrated, usually with high uptake. Small tumors (greater than or equal to 0.7 cm in diameter), however, showed variable uptake, from 0-4+. Thus, tumors within one patient were as variable in uptake as tumors between patients. Immunologic studies of melanoma tumor antigens have shown a similar variability. It is suggested that antigenic heterogeneity is responsible for the variable scintigraphic demonstration of such tumors.

Scintigraphic detection of metastatic melanoma using indium 111/DTPA conjugated anti-gp240 antibody (ZME-018).

We evaluated the toxicity, pharmacokinetics, and localization of a monoclonal IgG2 alpha murine anti-human melanoma (gp240) antibody (ZME-018) that recognizes a tumor-associated cell surface glycoprotein of 240,000 molecular weight present in most melanomas. The antibody was conjugated with DTPA (diethylenetriamine pentaacetic acid) and labeled by chelation of 111In. One mg of antibody labeled with 5 mCi of 111In was infused, together with 0 to 40 mg of "cold" carrier ZME-018. The blood clearance, urinary excretion, and in vivo localization were determined in 26 patients. Scintigraphic images were obtained at 24 hours and 72 hours in all patients. Mild toxicity occurred in one patient. The half-time clearance of labeled monoclonal murine antibody (MoAb) from the blood increased from 16.1 hours at an antibody dose of 1 mg to 35.9 hours at 40 mg. Males showed faster clearance from the blood than did females or a single castrated male, perhaps due to selective concentration of antibody in the testes. Nonspecific uptake in liver, spleen, bone marrow, and intestine was seen in all patients. The percentage of known metastatic foci detected increased with the total dosage of antibody, from 23% at doses less than or equal to 5 mg, to 65%, 87% and 78% for 10, 20, and 40 mg, respectively. We conclude that at doses of greater than or equal to 10 mg, ZME-018 is a safe and potentially useful agent for the scintigraphic detection of metastatic malignant melanoma.

Splenosis: a complicating factor in total abdominal hysterectomy.

A case of pelvic splenosis is presented to discuss preoperative investigation and to describe surgical difficulties that may be encountered. Surgery should only be undertaken when warranted by troublesome symptoms. Removal of asymptomatic ectopic splenic tissue is contraindicated.

Problems in the imaging diagnosis of hepatoma.

Two problem cases in the imaging diagnosis of hepatoma are reported. In both, a defect on the standard liver scan showed preferential gallium uptake. Ultrasound findings for a mass lesion were inconsistently present or absent. However, in the given clinical setting, a diagnosis of hepatoma was made. The microscopic changes suggested that the poor ultrasound demonstration of the tumors was due to marked fibrosis of the liver both outside and inside the tumor.

Nuclear medicine imaging in rhabdomyolysis.

A case of severe rhabdomyolysis is reported in which, some seven and one-half weeks after its occurrence, a gallium scan was strongly positive, due to abscess formation in the damaged muscle. A bone scan was weakly positive in the same area, due to gallium photons. A review of the the reported cases reveals that bone scans are a very sensitive indicator of acute muscle damage and are useful to monitor its repair.

Increased incidence of lymphomas in survivors of the host-versus-graft syndrome.

When (SB)F1 spleen cells were injected into perinatal parental B strain mice a lethal runting syndrome was induced. The survivors showed a significantly increased incidence of lymphomas in old age. The tumors occurred much later and less frequently than in the reverse reaction, B leads to (SB)F1 GVHD.

Treatment of spontaneous murine lymphomas with syngeneic lymphoid cells.

Syngeneic thymus grafts and spleen cells were administered to thymectomized and intact (C57BL/1XA)F1 mice with spontaneous lymphomas. Their life span was prolonged significantly compared to untreated tumor-bearing controls. Dramatic clinical and histologic evidence of tumor regression was observed.

Tumor induction in host-versus-graft disease. I. Clinical and pathologic features.

Perinatal C57BL/1 mice given injections of (SJL/J X C57BL/1)F1 spleen cells developed a highly lethal runting syndrome, designated host-versus-graft disease (HVGD). The mortality was related to the dosage of F1 cells. Acute pathologic changes resembled those occurring in parent leads to F1 graft-versus-host disease (GVHD), except for more pronounced plasmacytosis. Mice suffering from HVGD recovered clinically with no sequelae except for a slight increase in the incidence of lymphomas over control mice. Such mice were hyperreactive to F1 cells utilized to initiate the original HVGD syndrome. Most of the tumors developed in those animals receiving the initial injection of F1 spleen cells within 24 hours of birth. Tumor incidence was unrelated to the clinical severity of HVGD. By contrast, GVHD in the same strain combination resulted in a much higher incidence of lymphomas in a much shorter time. Parental strain cells were detectable in the F1 hosts up to the time of tumor development. HVGD has a low tumor induction potential; GVHD has a high tumor induction potential.