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Biomedical subjects

J B Grogan

Publications and source records attributed to J B Grogan.

At least 73 records · Page 4Linked to original sources

Immunochemotherapy of hepatoma in rats.

Immunoglobulin G prepared by immunization of rabbits with rat Novikoff ascites tumor cells was prepared and found to by cytotoxic to Novikoff cells and rat lymphocytes. A chlorambucil conjugate was prepared and found to have similar qualities in vitro. Three day culture systems were prepared with various test substances and the immunoglobulin was shown to markedly depress cell multiplication. The chlorambucil conjugate appeared to be more efficacious than the immunoglobulin alone in inhibiting cell growth. In vivo studies revealed a total inhibition of tumor formation in animals treated with the immunoglobulin-chlorambucil conjugate whereas all control groups had 50 to 100 per cent mortality. No systemic toxicity was apparent. These studies indicate that tumor-specific immunoglobulin bound to chlorambucil presents a feasible method of delivering tumoricidal drugs to cancer in body cavities and of treating tumors with an accessible blood supply.

Animals↗

Neutrophil function in clinical kidney allograft recipients.

The peripheral blood neutrophils from 17 kidney transplant recipients were studied for their ability to phagocytose and kill Pseudomonas aeruginosa in vitro. Practically all of the percent phagocytosis values were within the normal range but many of the neutrophil samples demonstrated a reduced ability to kill ingested P. aeruginosa, particularly within the 3 month period immediately after transplant. Of the 17 patients studied, ten were found to have neutrophils with a reduced capacity to kill the test bacteria. These defects in bactericidal capacity were found in patients who received antihuman-lymphocyte globulin (ALG), large doses of methylprednisolone for rejection, and mostly in subclinical infection with Pseudomonas or other gram-negative bacterial species.

Antibodies↗

Organ specificity in hyperacute rejection of canine heart and kidney allografts.

To clarify the organ specific nature of hyperacute rejection, 14 puppies were presensitized by multiple skin grafts and spleen cell injections prior to receiving either a heart or kidney allograft from the respective donors. Of this group, 7 received orthotopic heart allografts and 7 received kidney allografts. All heart allografts were rejected between 3 and 28 hours, and all kidneys between 0 and 24 hours as judged by cessation of urine flow from the ureterostomies. In contrast, all 11 animals in a recent series of heart allografts in non-sensitized puppies survived the operation, and rejected between 7 and 17 days. There was a significant correlation in both groups between preoperative cytotoxic antibody titer in the recipient serum and graft survival time. The preoperative titers were all above 1:1,024 but were greatly reduced within 2 hours after transplantation. At the time of rejection, antibody could be eluted from the rejected organs. In contrast to the kidneys, in which 2 of 7 grafts ceased to function immediately after revascularization, all hearts resumed beating and functioned well for at least several hours. At autopsy, the myocardium was pale and edematous and histologically polymorphonuclear leukocytes were prevalent in and around the small vessels and among myofibers. Both IgG and IgM antibody was detected in sarcolemma of the myocardium and to a lesser extent in the intima and adventitia of the small vessels by the fluorescent antibody technique. Biopsies of the rejected kidneys showed polymorphonuclear leukocyte infiltration, typical of hyperacute rejection. Marked fluorescence of IgG and IgM in the glomeruli and peritubular capillaries was observed. This study indicates that both organs rejected hyperacutely in our experimental model and participation of the preformed antibody in effecting this change was strongly suggested.

Animals↗

Alterations in the bactericidal ability of rabbit alveolar macrophages as a result of tumbling stress.

Bacteriologic and electron microscopic studies support observations that the degradative phase of the phagocytic process in rabbit alveolar macrophages is altered by subjecting the animals to tumbling stress. Macrophages from control and stressed rabbits have similar ultrastructural features. In vitro incubation of macrophages from stressed animals with Pseudomonas aeruginosa showed that the process of bacterial ingestion was not impaired, nor were the numbers of bacteria ingested decreased as compared to control macrophages. However, the ability of macrophages from stressed animals to kill ingested bacteria was significantly decreased. Bacterial plate counts after 30 minutes incubation showed that approximately 70% of the ingested organisms had been killed by control macrophages, whereas there was practically no kill by macrophages from stressed animals even after 90 minutes. Electron microscopy demonstrated extensive degradation of Pseudomonas within phagocytic vacuoles of control macrophages. These changes consisted of cytoplasmic swelling, clumping of nuclear material and disruption of the bacterial cell wall. In contrast, bacterial degradation was not observed within macrophages from stressed animals at any of the intervals studied (up to 90 minutes after rotation). This form of stress thus appears to deprive the alveolar macrophages of the ability to destroy ingested microorganisms, a factor which may be important to the establishment of pulmonary infections.

Animals↗