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Biomedical subjects

K A Reimann

Publications and source records attributed to K A Reimann.

53 records · Page 3Linked to original sources

An activated CD8+ lymphocyte appears in lymph nodes of rhesus monkeys early after infection with simian immunodeficiency virus.

Although alterations in T lymphocyte subset distribution and function in the peripheral blood of HIV-infected humans are well defined, the extent to which these reflect changes in other lymphoid compartments is unclear. We have characterized the coincident changes in PBL and lymph nodes (LN)1 after simian immunodeficiency virus of macaques (SIVmac) infection of rhesus monkeys. Whereas no consistent change in CD8+ PBL was noted during the first 60 d after infection, CD8+ lymphocytes increased significantly in number in LN. These CD8+ LN lymphocytes exhibited an increased expression of MHC class II and a decreased expression of leukocyte adhesion molecule-1, suggesting that they were activated, but interestingly did not express CD25 (IL-2 receptor). Moreover, there was no evidence that these CD8+ LN cells were proliferating, suggesting that they had migrated to the LN. These changes in the LN CD8+ lymphocyte population preceded any detectable change in the light microscopic appearance of the LN. When SIVmac-specific effector T cell responses were assessed, the magnitude of virus-specific effector activity was nearly identical in the PBL and LN of each monkey studied. However, the presence of SIVmac-specific effector cells in the LN did not correlate with the presence of CD8+, MHC class II+ cells. These findings suggest that this numerically important CD8+ lymphocyte subpopulation may serve a regulatory function.

Animals↗

Extraskeletal osteosarcoma in two dogs.

Extraskeletal osteosarcoma (ESOS) of the spleen and jejunum was diagnosed in 2 dogs. As an extremely uncommon type of tumor that has proven difficult to treat, ESOS is associated with high rate of local recurrence and metastatic disease. Extraskeletal osteosarcoma principally affects older dogs, has no apparent breed predilection, and may develop more frequently in males. The cause of ESOS is unknown, but may involve malignant metaplasia of pluripotential mesenchymal cells into osteoblasts. Macroscopically, ESOS usually is observed as a hard mass and may appear similar to calcified hematoma or myositis ossificans. The classic radiographic appearance of ESOS is a soft tissue mass with focal mineralization and without adjacent bone involvement.

Animals↗

Effect of recombinant soluble CD4 in rhesus monkeys infected with simian immunodeficiency virus of macaques.

The CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV-1) and a soluble truncated form of CD4 produced by recombinant DNA technology is a potent inhibitor of HIV-1 replication and HIV-1-induced cell fusion in vitro. Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIVMAC), a virus closely related to HIV-1, develop an AIDS-like syndrome, and so provide an important model for the evaluation of potential AIDS therapies. We have assessed the therapeutic effect of recombinant soluble CD4 in SIVMAC-infected rhesus monkeys. Virus was readily isolated from peripheral blood lymphocytes and bone marrow cells of these animals before starting treatment with soluble CD4, but became difficult to isolate soon after treatment had begun. Moreover the diminished growth of both granulocyte-macrophage and erythrocyte progenitor colonies from the bone marrow of these monkeys rose to normal levels during treatment. These findings indicate that soluble CD4 could prove valuable in the treatment of AIDS.

Animals↗

Prolongation of primate renal allograft survival by anti-Tac, an anti-human IL-2 receptor monoclonal antibody.

In an effort to produce specific immunosuppression through the targeting of those lymphocytes expressing cell surface interleukin 2 receptors in response to an allograft, the anti-human IL-2 receptor monoclonal antibody anti-Tac was administered to cynomolgus monkeys receiving renal transplants. The data demonstrate that anti-Tac produces a significant delay in renal allograft rejection and prolongs host survival in cynomolgus monkeys. Though higher doses of anti-Tac produce modest delays in rejection, there was a surprising finding of greatly prolonged survival in three of five monkeys treated with much lower doses of anti-Tac. Anti-Tac was not shown to be synergistic with cyclosporine in this model. Animals treated with anti-Tac developed high titers of antibodies against the murine monoclonal antibody after 6-8 days of treatment, associated with the disappearance of plasma anti-Tac staining of activated lymphocytes as measured by flow cytometry. The data confirm the utility of the IL-2 receptor as a target for immunosuppressive therapy, and suggest that investigations of dosage and of methods to reduce the immunogenicity of anti-IL-2 receptor agents may be beneficial.

Animals↗

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. V. Evidence that humoral immune response to monoclonal antibodies and immunotoxin conjugates abrogates their cytotoxic activity.

Monoclonal antibodies, either alone or conjugated to toxins, hold promise as important therapeutic agents. However, the immune response to these foreign protein agents may markedly limit their therapeutic utility in vivo. We have administered both an interleukin-2 receptor-specific monoclonal antibody (anti-IL-2R) and a CD2-specific monoclonal antibody linked to the ribosome-inactivating protein gelonin to macaque monkeys. The monkeys developed high-titer antibody responses to mouse Ig and, when immunotoxin was administered, to the toxin gelonin. Their antimouse Ig antibody responses were broadly reactive with mouse Ig of differing idiotypes and isotypes. Furthermore, sera from these monkeys blocked the in vitro cytotoxic effect of anti-IL-2R or immunotoxin. This blocking was mediated by both the antimouse Ig and the antigelonin antibodies. Serum from a monkey infused with one CD2-specific monoclonal antibody blocked the in vitro cytotoxicity of two other isotypically different CD2-specific monoclonal antibody conjugates. In addition, this serum blocked the in vitro cytotoxicity of a gelonin-monoclonal antibody conjugate of an unrelated specificity. These data indicate that the immune response to some monoclonal antibodies and toxins might preclude the later use of this class of substances in an individual. Therefore, strategies for the parental therapeutic use of monoclonal antibodies and immunotoxins must take into consideration the possible limiting effects of the humoral immune response to these agents.

Animals↗

Clinicopathologic characterization of canine juvenile cellulitis.

The syndrome of canine juvenile cellulitis was observed and characterized throughout its clinical course when it occurred spontaneously in a litter of dogs. Histologically, pyogranulomatous inflammation was seen in facial skin and mandibular and superficial cervical lymph nodes of affected dogs. The predominant inflammatory cell characterized by light and electron microscopy and by immunohistochemical staining was an epithelioid macrophage. The same pyogranulomatous inflammatory process was seen in a lymph node anatomically distant from the site of apparent disease. Interestingly, a littermate with neither clinically evident dermal lesions nor lymphadenopathy had histologic evidence of a milder, but similar inflammatory process in a mandibular lymph node. The observation of canine juvenile cellulitis in clusters of dogs between 1 and 4 months of age and its apparent systemic nature suggest an infectious etiology. Bacterial, fungal, or viral agents were not isolated from affected lymph nodes. Attempts to transfer the disease by inoculation of neonatal puppies with tissue from affected dogs were also unsuccessful.

Animals↗

Tuberculosis in five basset hounds.

Five Basset Hounds (2 females and 3 males) under the age of 5 years, acquired systemic tuberculosis. We suspected tuberculosis in one dog, because it had histologic lesions similar to those in 4 dogs in which bacteria were identified as Mycobacterium avium complex. A review of canine tuberculosis revealed a similar diagnosis in a Basset Hound. The association of this infection in Basset Hounds suggests an inherited immunologic defect. Results of our survey suggest that the defect might exist in cell-mediated immunity.

Animals↗

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. IV. Cytotoxic effect of an anti-T11-gelonin immunotoxin.

The cytotoxic effect of a lymphocyte-specific immunotoxin formed by disulfide conjugation of an anti-T11 monoclonal antibody with the ribosome-inactivating protein gelonin was assessed in vitro on peripheral blood T cells and in vivo on splenic and lymph node T cells of macaque monkeys. This immunotoxin was cytotoxic to proliferating peripheral blood T cells in vitro as measured by both direct and indirect assays. Two sequential intravenous infusions into macaque monkeys achieved plasma concentrations of immunotoxin far in excess of those shown to be cytotoxic for cultured T cells and coated all T cells in lymph nodes and spleen with intact immunotoxin for four days. However, the cytotoxic effect of the immunotoxin on T cells in vivo was considerably less than that predicted by the in vitro studies. Further experiments suggested that the state of activation of the targeted T cell population in vivo, or the appearance of anti-immunotoxin antibodies, which occurred in all infused monkeys, might attenuate immunotoxin-mediated cell killing in vivo. These studies illustrate the significant differences between the action of immunotoxin conjugates in vitro, and those seen when these conjugates are utilized as therapeutic agents in vivo.

Animals↗

Thyroid and immunologic status of dogs with perianal fistula.

Lymphocyte-proliferation responses, absolute lymphocyte counts, and thyrotropin-stimulation responses were determined in 33 dogs with perianal fistula; serum immunoglobulin values also were determined in 15 of the 33 dogs. Lymphocytes were stimulated with concanavalin A, pokeweed mitogen, and phytohemagglutinin and were cultured with medium containing normal pooled canine serum or fresh patient's autologous serum. Initially, lymphocytes from 9 dogs (27.3%) had depressed stimulation responses to greater than or equal to 1 phytomitogen, and 4 of the 9 dogs had absolute lymphopenia. One month after recovery in these 9 dogs, lymphocytes from 4 dogs (66.7%) had normal proliferation responses. Of immunoglobulin determinations in 15 dogs, serum IgA values were 32 to 185 mg/dl (mean, 69 +/- 10 mg/dl) and were low in 2 dogs (13%), and serum IgM values were 48 to 610 mg/dl (mean, 263 to 46 mg/dl) and were high in 8 dogs (53%). Serum IgG values were 1,050 to 3,220 mg/dl (mean, 2,339 +/- 165 mg/dl) and were high in 10 dogs (71%). After thyrotropin stimulation, 1 dog was considered hypothyroid. Neither pathogenesis nor prognosis of canine perianal fistula was clarified via immunoglobulin concentrations or absolute lymphocyte counts. Based on lymphocyte-proliferation assays, suppression of cell-mediated immunity was probably a result of perianal fistula, rather than a cause of the fistula.

Animals↗

Feline sporotrichosis: a report of five cases with transmission to humans.

Sporotrichosis was diagnosed in five cats. Seven humans exposed to these cats subsequently developed the disease. All feline cases developed draining ulcers, and in four of five cases there was disseminated cutaneous involvement. Histologically, numerous Sporothrix organisms were noted in cutaneous lesions and overlying exudate. The seven humans who became infected were involved in cleaning and medicating cats with the disease; all human patients developed a localized lymphocutaneous form of sporotrichosis. In four of the human cases there was no history of an associated penetrating wound. The large number of Sporothrix organisms is a distinct feature of feline sporotrichosis and indicates that the cat may be the only domestic animal species that can readily transmit this disease to humans. In addition, any contact with the draining lesions of affected cats offers the potential for human infection.

Adult↗

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. Delivery of ribosome-inactivating proteins to spleen and lymph node T cells.

The selective delivery in vivo of a T lymphocyte-specific monoclonal antibody and immunotoxin conjugates to T cells in lymph node and spleen was assessed in rhesus monkeys. A transient coating of all T lymphocytes in the lymph nodes and spleens of healthy rhesus monkeys could be achieved after infusion of unconjugated anti-T11. Because derivatized antibody is cleared more rapidly than unconjugated antibody, it was necessary to infuse a higher dose of immunotoxin than antibody alone to achieve saturation of the lymphocyte binding sites with anti-T11. When sufficient antibody-toxin conjugate was infused, toxin was readily demonstrable on lymph node and spleen T cells by 16 h after infusion. This demonstration that toxins can be successfully delivered with specificity to target T cell populations in the monkey suggests that killing of restricted cell populations in vivo should be feasible.

Animals↗

Humoral immune responses to T cell tropic retrovirus simian T lymphotropic virus type III in monkeys with experimentally induced acquired immune deficiency-like syndrome.

The T cell tropic retrovirus of macaque monkeys simian T lymphotropic virus type III (STLV-III) has morphologic, growth, and antigenic properties indicating that it is related to human T cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), the etiologic agent of the acquired immune deficiency syndrome (AIDS) of humans. STLV-III has recently been shown to induce an AIDS-like disease in macaque monkeys. In this study the humoral immune responses of six experimentally infected monkeys have been characterized to determine whether certain parameters of the antibody response to the virus might be predictive of the clinical outcome of this infection. Two distinct patterns of antibody responses were found. Four animals that died within 160 d of inoculation developed low titer anti-STLV-III antibody responses that recognized only the viral envelope protein, and progressive declines in total plasma IgG levels and absolute peripheral blood T4 lymphocyte numbers. The two animals that lived longer (one died at 352 d, the other remains alive at 430 d) developed high titer anti-STLV-III antibody responses that recognized both viral envelope and core proteins, increases in total plasma IgG, and a later decrease in number of peripheral blood T4 lymphocytes. Interestingly, the single animal that has remained clinically healthy after infection was the only one to develop detectable STLV-III neutralizing antibodies.

Acquired Immunodeficiency Syndrome↗

Immunologic profiles of cats with persistent, naturally acquired feline leukemia virus infection.

Several immunologic responses were measured in 13 healthy cats with naturally acquired, persistent feline leukemia virus (FeLV) viremia from 4 multiple-cat households and were compared with responses from 28 of their healthy, non-FeLV-viremic housemates. Significant differences (P = less than 0.05) were not observed between results of FeLV-viremic and nonviremic cats for peripheral blood leukocyte or lymphocyte count, percentage of peripheral blood mononuclear cells able to form rosettes with guinea pig RBC or with antibody- and complement-coated sheep RBC, lymphocyte proliferative response to concanavalin A or pokeweed mitogen, or serum immunoglobulin G concentration. Seemingly, persistent FeLV viremia, when naturally acquired, may exist for some time without lymphopenia or a marked loss of mitogen-induced lymphocyte proliferation.

Animals↗

Contrasting reflexes evoked by chemical activation of cardiac afferent nerves.

Afferent neurons within cardiac sympathetic nerves can reflexly excite central sympathetic outflow. However, their contribution to cardiovascular control remains unclear because they are potentially opposed by inhibitory reflexes of cardiac vagal or arterial baroreceptor afferent origin. It was considered that sympathetically mediated, excitatory responses might be more prominent when initiated by chemical stimulation. In chloralose-anesthetized, vagotomized, sinoaortic-denervated cats, epicardial or intracoronary administration of bradykinin or potassium chloride evoked renal nerve excitation and pressor responses mediated by cardiac sympathetic afferent nerves. When upper thoracic sympathetic nerves were severed, and vagal afferent nerves remained intact, bradykinin and potassium chloride produced inhibition of renal nerve activity and depressor responses. When sympathetic and vagal components of cardiac innervation remained intact, these substances produced excitation, inhibition, or no change in sympathetic outflow. Excitation occurred as often as inhibition. A similar pattern was observed when arterial baroreceptor nerves remained intact. These data illustrate that cardiac sympathetic afferent neurons can have significant excitatory influences on the cardiovascular system in spite of opposition by inhibitory afferent groups.

Afferent Pathways↗

Factitious hyperkalemia in dogs with thrombocytosis. The effect of platelets on serum potassium concentration.

To determine the effect of platelet count on the accurate assessment of serum electrolyte concentrations, simultaneous platelet counts and electrolyte determinations were performed on serum and plasma from 40 dogs. Dogs were grouped according to platelet count as follows: thrombocytopenic (less than 150,000/microliters), normal (150,000 to 600,000/microliters), or thrombocytotic (greater than 600,000/microliters). Serum potassium concentration was significantly higher than plasma potassium concentration in normal dogs (mean difference, 0.63 +/- 0.17 mEq/l) and in dogs with thrombocytosis (mean difference, 1.55 +/- 0.73 mEq/l). This difference in potassium concentration between serum and plasma was positively correlated with platelet count (r2 = 0.86). In the blood of dogs with thrombocytosis, the serum-plasma potassium difference was further increased when the time period between blood collection and separation of serum or plasma from cells was lengthened. Differences between serum and plasma concentrations of sodium or chloride were not seen in any platelet group. These results suggest that a portion of the measured serum potassium concentration is released from platelets during the clotting process. In fact, profound elevations in serum potassium concentrations can occur factitiously in dogs with thrombocytosis. Therefore, the actual concentration of potassium in blood is determined more accurately by measuring the plasma concentration rather than the serum concentration of this electrolyte.

Animals↗