Giant renal oncocytoma.

We report the largest renal oncocytoma excised at the initial presentation and the second largest renal oncocytoma in published reports. Despite a tendency for renal oncocytomas to be relatively small and asymptomatic compared with renal cell carcinomas, these lesions cannot be reliably differentiated preoperatively. The variable nature of presentation and overlap of radiographic characteristics between these lesions complicates their clinical differentiation. The present case illustrates the difficulty in the preoperative diagnosis of even very large, enhancing renal masses and reinforces the inclusion of renal oncocytoma in the differential diagnosis of these lesions.

Emergency craniotomy in a rural Level III trauma center.

Patients with closed head injury and expanding epidural (EDH) or subdural (SDH) hematoma require urgent craniotomy for decompression and control of hemorrhage. In remote areas where neurosurgeons are not available, trauma surgeons may occasionally need to intervene to avert progressive neurologic injury and death. In 1990, a young man with rapidly deteriorating neurologic signs underwent emergency burr hole decompression of a combined EDH/SDH at our hospital, with complete recovery. In anticipation of future need, five surgeons at our rural, American College of Surgeons-verified Level III trauma center participated in a neurosurgeon-directed course in emergency craniotomy. Since January 1, 1991, 792 patients have been entered into the trauma registry, including 60 with closed head injury and Glasgow Coma Scale (GCS) score of 13 or less. All but seven were transferred to a regional Level II trauma center, which is a minimum flight time of 1 hour each way. All patients with EDH (5) and 2 of 14 with SDH were deemed too unstable for transport and underwent burr hole decompression followed by immediate transfer. All craniotomies were approved by the consulting neurosurgeon and were done for computed tomography-confirmed lesions combined with neurologic deterioration as demonstrated by (1) GCS score of 8 or less, (2) lateralizing signs (dilated pupil, hemiparesis), or (3) development of combined bradycardia and hypertension. One patient with a GCS score of 3 on arrival died. Seven survivors (mean follow-up, 3.9 years; range, 1-6.5 years), including the index case, function independently, although one survivor has moderate cognitive and motor impairment. We conclude that early craniotomy for expanding epidural and subdural hematomas by properly trained surgeons may save lives and reduce morbidity in properly selected cases when timely access to a neurosurgeon is not possible.

Antibodies against cortisol block suppressive effects of corticosteroids on lymphocytes in vitro.

Lymphocyte transformation assays were used to test the ability of antibodies against cortisol to reduce bioactivity of corticosteroids in vitro. Mononuclear cells were separated from whole bovine blood and cultured in the presence of PHA alone, PHA + steroid, PHA + steroid + anticortisol, or PHA + steroid + anti-bovine serum albumin. Tritiated thymidine uptake was determined for all groups during the last 24 hr of a 72-hr culture period by scintillation counting. Polyclonal anticortisol against cortisol-bovine serum albumin conjugated in the 21 position was more effective in blocking cortisol activity than monoclonal anticortisol built against conjugates in the 3 position. The steroids that suppressed PHA-induced lymphocyte proliferation in a concentration-dependent manner were: cortisol, corticosterone, dexamethasone, prednisolone, 11-deoxycortisol, and 11-deoxycorticosterone. Aldosterone, cortisone, cholesterol, estradiol, and progesterone did not exhibit concentration-dependent effects and, thus, were not considered suppressive. These concentration-independent steroids were also the least suppressive (with the exception of aldosterone). Anticortisol was able to reduce bioactivity of suppressive corticosteroids that had an 11-hydroxy group, suggesting the antibody was primarily made against this site. Anti-BSA was not effective in blocking corticosteroid activity, but it did enhance proliferation of lymphocytes if added in combination with weakly suppressive steroids. Anticortisol also had an enhancing effect when added with some weakly suppressive steroids. We conclude that antibodies against cortisol are capable of reducing bioactivity of steroids that strongly suppress lymphocyte proliferation. Additionally, the 11-hydroxy group may be an important antigenic determinant of steroid molecules.

Lessons from caprine and ovine retrovirus infections.

Two lentiviruses that infect sheep and goats have been shown to be closely related to the human immunodeficiency virus (HIV). These ungulate lentiviruses cause a spectrum of diseases, including arthritis in their natural hosts. The molecular and cellular biology of these viruses as well as possible pathogenic mechanisms is compared to HIV-1 in order to identify common features and significant differences between the human and animals pathogens.

Production of arachidonic acid metabolites by caprine alveolar macrophages.

The in vitro release of arachidonic acid (AA) metabolites from caprine alveolar macrophages (CAM) stimulated with the calcium ionophore A23187 or opsonized zymosan was examined. Leukotriene B4 [5(S),12(R)-6,14-cis-8,10-trans-dihydroxyeicosatetraenoic acid] was the major AA metabolite elicited with either agonist; smaller amounts of 12- and 5-mono-hydroxyeicosatetraenoic acid (HETE), and 12-hydroxyheptadecatrienoic acid (HHT) were also detected. Zymosan stimulation also caused the release of very small quantities of prostaglandins E2 and F2 alpha, and thromboxane B2. Our report is the first to describe arachidonic acid metabolism in CAM.

Augmentation of lymphocyte and macrophage proliferation by caprine arthritis-encephalitis virus contributes to the development of progressive arthritis.

Infection by the lentivirus, caprine arthritis-encephalitis virus (CAEV), may lead to an intermittent arthritis due to the presence of lymphocytes and macrophages in synovial membranes. We have observed that the presence of CAEV increases the division of lymphocytes and macrophages. In association, antigen-induced arthritis is more severe in goats concurrently infected by CAEV than in noninfected goats. From these observations we propose that infection by this lentivirus increases reactivity of lymphocytes and macrophages to immune and nonimmune stimuli, leading to the increased likelihood of progressive arthritis in infected animals.

Increased macrophage division in the synovial fluid of goats infected with caprine arthritis-encephalitis virus.

Macrophages are a major component of the arthritic lesions induced by the lentivirus caprine arthritis-encephalitis virus (CAEV). Using autoradiography and the appearance of mitotic figures to detect dividing macrophages, we found that 2.1% +/- 0.2% of synovial fluid macrophages from uninfected goats are dividing and that after infection with CAEV the percentage increases three- to sixfold. The enhanced macrophage division was not associated with increased dividing of blood monoblasts. The amount of macrophage division correlated with two measures of arthritis: joint swelling and the number of synovial fluid macrophages. Induction of an immune response in the joints of CAEV-infected goats increased the number of dividing macrophages. The synovial fluid of infected animals was mitogenic for macrophages from infected animals in amounts that correlated with the amount of macrophage division occurring in the joints. Activated lymphocytes produced nondialyzable lymphokines mitogenic for macrophages from CAEV-infected goats but not from uninfected goats. These results suggest that in situ macrophage division contributes to the lesions induced by CAEV and that infection leads to greater responsiveness of macrophages to mitogenic factors produced by lymphocytes.

Contribution of various host factors to resistance to experimentally induced bacterial endotoxemia in calves.

The reactions of 15 calves to IV administered bacterial lipopolysaccharide was investigated and was correlated with the capacity of 2 host defense mechanisms. The calves had a wide range of changes in clinical response, total WBC count, plasma lactate dehydrogenase (LD) activity, reaction to intradermally inoculated lipid A, and rectal temperature response. The early rectal temperature response of an individual calf was correlated with plasma LD activity, indicating a relationship between cell damage and fever. The concentration of antibody against lipid A at the time of lipopolysaccharide inoculation was negatively correlated with the rectal temperature changes recorded during endotoxemia, suggesting a protective ability of antibody. The capacity of a plasma inhibitor of lipopolysaccharide-mediated clotting of limulus amebocyte lysate was correlated with increases in plasma LD activity. Therefore, antibody to lipid A probably is involved in protection of cattle during endotoxemia, but the plasma lipopolysaccharide inhibitor actually may potentiate lipopolysaccharide toxicity.

Lentivirus infection augments concurrent antigen-induced arthritis.

Experimental antigen-induced arthritis was compared in normal goats and goats infected with caprine arthritis-encephalitis virus. Although acute arthritis was the same in infected and uninfected animals, the disease lasted 16 weeks longer in the caprine arthritis-encephalitis virus-infected goats. Our findings suggest that the arthritis caused by this virus is due to events other than, or in addition to, the immune reaction to viral antigens.

Locally dividing macrophages in normal and inflamed mammary glands.

Goat mammary macrophage division in vivo was assessed by detection of mitotic figures, by autoradiographic measurement of the uptake of 3H thymidine, and by a 96-well proliferation assay. Autoradiography revealed that 3.74 +/- 0.77% of nonstimulated mammary macrophages were actively synthesizing DNA. Eight days of sterile inflammation, induced by lipopolysaccharide or thioglycollate, increased mammary macrophage division (10.9 +/- 2.1%). The division increased within 2 h after inducing inflammation with thioglycollate. After 1 day, the rate of division decreased, and another increase occurred 3-4 days later. The high rate of division was maintained for greater than 60 days after the induction of sterile inflammation. Division was further shown to occur by injecting 3H-thymidine directly into the mammary gland, harvesting the macrophages 1.5 h later, and determining incorporation by autoradiography. The results of all assays of division were in agreement, suggesting they reflected the same event. The dividing cells were nonspecific esterase-positive, adherent, motile, phagocytic, and had morphological characteristics of macrophages.

Stimulation and killing of bovine mononuclear leukocytes by bacterial lipopolysaccharide (endotoxin).

Bovine adherent mononuclear leukocytes were incubated with bacterial lipopolysaccharides (LPS) in vitro, and these cells produced a factor that increased the blastogenic reaction of mouse thymocytes to concanavalin A. This factor most resembles interleukin 1. The LPS were also cytotoxic for bovine adherent mononuclear leukocytes in a dose-and time-dependent manner. Cytotoxicosis was determined by the release of cytoplasmic lactic dehydrogenase. This cytotoxicosis was blocked by treating the cells with corticosteroids. Variation in the reaction to LPS occurred in cells collected from the same cow on different days and from cells collected from different cows.

Antigenic cross-reactivity between caprine arthritis-encephalitis, visna and progressive pneumonia viruses involves all virion-associated proteins and glycoproteins.

Antigenic relatedness between the virion-associated proteins of caprine arthritis-encephalitis, visna and progressive pneumonia viruses was examined. Antigenic cross-reactivity was assessed by immunoprecipitation of disrupted, radiolabelled virus with goat, sheep and rabbit antisera, followed by resolution of the immunoprecipitation products by SDS-polyacrylamide gel electrophoresis. The results indicate that antigenic cross-reactivity between the caprine and ovine virus isolates involves all of the major virion-associated proteins and glycoproteins. The common antigenic determinants exhibited by virion structural proteins are immunogenic in goats, sheep and rabbits.

Cellular and lipopolysaccharide subunit requirements for the caprine lymphoblastogenic response to endotoxin.

Caprine B lymphocytes were established as the cell type that divided when cultured with lipopolysaccharide (LPS), and lipid A was defined as the in vitro mitogenic component of LPS. The conclusion that the caprine B lymphocyte was stimulated by LPS was based on 3 observations: (i) Numbers of B lymphocytes increased in cultures containing LPS, but not in unstimulated or concanavalin A-stimulated cultures, (ii) mixtures of T lymphocytes and monocytes did not incorporate tritiated thymidine when LPS was added, and (iii) removal of monocytes from mixtures of T and B lymphocytes did not reduce the LPS-stimulated reaction. Stimulation of B lymphocytes by LPS occurred when less than 1% monocytes were present and was augmented by greater than 5% monocytes. The lipid A subunit of LPS was most likely responsible for mitogenesis, since purified lipid A stimulated lymphocytes and the addition of polymyxin B, a specific inhibitor of lipid A activity, blocked the lymphocyte reaction.

Continuous cultivation of equine lymphocytes: evidence for occasional T cell-like maturation events in horses with hereditary severe combined immunodeficiency.

Peripheral blood mononuclear cells (PBMC) from 14 foals with hereditary severe combined immunodeficiency (SCID) were studied to determine the extent of lymphocyte differentiation that occurs in this disorder. PBMC from all 14 horses had the morphologic characteristics of large granular lymphocytes (LGL). Cells from only one of 14 horses were responsive to phytolectin stimulation in a standard blastogenesis assay; however, PBMC from all 14 horses proliferated in continuous culture in the presence of partially purified interleukin 2. Furthermore, there were differences in the growth patterns of these cultured cells that correlated with their ability to respond to phytolectin stimulation. PBMC obtained from the 13 phytolectin-unresponsive foals survived in culture for only 4 to 5 wk, divided very slowly, developed large granules composed primarily of calcium phosphate, and accumulated high concentrations of histamine. In contrast, PBMC from the phytolectin-responsive SCID foal proliferated in continuous culture for over 100 days, divided as rapidly as normal equine PBMC under identical culture conditions, and did not accumulate granules or histamine. These observations indicate that lymphoid cell differentiation occurs in some horses with SCID even though the identity of the LGL is unresolved. Two possibilities are that LGL are products of a pathway separate from that of lymphocytes or that LGL are precursors of mature lymphocytes.

A sequential study of virus expression in retrovirus-induced arthritis of goats.

Persistent infection by the retrovirus caprine arthritis--encephalitis virus (CAEV) induces arthritis in goats which closely resembles rheumatoid arthritis. To examine the relationship between virus expression and development of clinical disease, ten goat kids were inoculated with CAEV and examined at successive intervals through 18 months post-infection. Virus was monitored in cell-free synovial fluid cells, serum and peripheral blood cells by titration, co-cultivation and immunofluorescent techniques. Virus was readily recovered from the synovial cavity of all animals during the first 4 weeks of infection, followed by a reduction and fluctuation in virus titres and ability to detect virus. Recovery of CAEV from peripheral blood cells occurred at low frequency while viraemia was rare. Results obtained over a period of 18 months indicate a positive association between virus expression in the synovial cavity and development of clinically detectable disease.

Experimental infection of sheep by caprine arthritis-encephalitis virus and goats by progressive pneumonia virus.

The lentiviruses, caprine arthritis-encephalitis virus (CAEV) and progressive pneumonia virus (PPV) of sheep, cause major diseases in their respective hosts; however, the infectivity of these viruses for closely related species has not been determined. Experiments were conducted to determine whether CAEV would infect sheep and whether PPV would infect goats. Upon inoculation with CAEV, lambs developed a nonsuppurative arthritis and antibody to CAEV, and the virus was isolated up to 4 months later. Exposure of 3 lambs to CAEV-infected adult goats did not lead to demonstrable infection after 18 months. Young goats inoculated with PPV replicated the virus and developed arthritis and antiviral antibody. These results demonstrate that these distinctly different lentiviruses may infect and cause diseases in species other than their accustomed host. Presently used techniques may not be effective in differentiating which lentivirus is responsible for infection of sheep and goats. Our results also indicate that mixing sheep and goats may adversely influence attempts to eradicate lentiviruses from these species.

Augmented T lymphocyte responses and abnormal B lymphocyte numbers in goats chronically infected with the retrovirus causing caprine arthritis-encephalitis.

Caprine arthritis-encephalitis is a retrovirus-induced disease resulting in lymphoproliferative lesions of the CNS and joints. Peripheral blood leukocytes of chronically infected goats were analyzed for the types of cells present and for their reactivity to viral antigen and polyclonal stimulants. Two of 9 infected goats had abnormal numbers of B lymphocytes--one elevated and the other deficient. Lymphocyte reactivity to viral antigens was transiently detectable by a lymphoblastogenic assay in 5 of the 9 goats. The reactive cells were peanut agglutinin-negative T lymphocytes. Concanavalin A induced more division in T lymphocytes of infected goats than in lymphocytes of noninfected goats, whereas the reactions to phytohemagglutinin, pokeweed mitogen, and bacterial lipopolysaccharide were no different in the 2 goat groups. It is concluded that goats infected by the caprine arthritis-encephalitis virus have antigen-reactive T lymphocytes and that infection promotes the response to a nonspecific T-cell stimulant.