Reversal of encephalomyocarditis virus-induced diabetes mellitus by islet transplantation.
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Biomedical subjects
Publications and source records attributed to R J Howard.
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This study demonstrates that large doses of human IgG can, if prepared by appropriate methods, be safely given intravenously. Antibody titers to CMV can be significantly elevated by administration of MIVIgG. While this is not a controlled trial, IgG therapy appears to be beneficial in renal transplant patients presenting with life-threatening infections.
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Short term in vitro cultivation has been used successfully for biosynthetic labelling of TCA precipitable macromolecules of Papua New guinean isolates of Plasmodium falciparum. Conditions satisfactory for completion of the asexual erythrocytic cycle were achieved with aa minimum of sophisticated equipment. The techniques used are described in detail and mention is made of possible applications to assessment of chloroquine resistance and the mode of action of inhibitory antisera.
Zoster immune plasma (ZIP) was evaluated for treatment of cutaneous disseminated zoster in immunocompromised hosts. Twenty patients were studied: 13 were enrolled in a double-blind protocol, five received ZIP under an open protocol, and two were observed without receiving a transfusion. In the double-blind study, eight patients actually received ZIP; five were given plasma lacking varicella-zoster virus antibodies (control plasma). The clinical course of zoster in the group given ZIP was the same as that of patients given control plasma or no transfusions. Because ZIP did not alter the clinical course of zoster and because zoster patients produced high-antibody titers without ZIP, we concluded that ZIP is not useful for treatment of cutaneous disseminated zoster and should be reserved for prevention or modification of varicella in exposed, susceptible immunocompromised patients.
A fistula formed between a false aneurysm of the renal artery, gallbladder, and duodenum after Dacron patch angioplasty for renal artery stenosis and led to massive gastrointestinal hemorrhage. The patient was successfully treated by renal artery ligation, nephrectomy, cholecystectomy, and closure of the duodenal fistula.
The intestinal changes brought about by rejection of Trichinella spiralis from mice were studied in relation to their effects on a concurrent infection with Hymenolepis microstoma, a cestode not normally rejected from mice. The rejection phase of T. spiralis was associated with a marked stunting of growth of H. microstoma given just before, during, or just after rejection of the nematode. The survival of H. microstoma was affected only when rejection of T. spiralis coincided with the intestinal phase of the cestode: if T. spiralis rejection was timed to occur after the scolex of the cestode had entered the bile duct there was no loss of H. microstoma. It is suggested that the adverse effects on growth and establishment of H. microstoma were due to the non-specific inflammatory component of the host's response to infection with T. spiralis.
In an attempt to generate large numbers of mice resistant to Plasmodium berghei and Babesia rodhaini to be used as donors of antibody-secreting cells for hybridoma production, various methods of inducing resistance to repeated challenge with infected blood cells have been explored. Although results of independent experiments varied markedly, prior injection of CBA/M mice with BCG, and prior infection of BALB/c mice with Plasmodium yoelii, were found to be manipulations capable of inducing resistance to P. berghei. A single dose of serum, harvested from resistant mice challenged several times with P. berghei, could transfer resistance against P. berghei to a proportion of naive CBA/H recipients. Although resistance to multiple B. rodhaini challenge could be induced in mice, in no situation was a host protective effect of a single high dose of serum demonstrated in naive recipients.
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Infection continues to be a major source of morbidity and the major source of mortality in renal transplant recipients who are susceptible to opportunistic infections. We recently reviewed all renal transplant recipients who had fungi cultured during a three year period. C. albicans and T. glabrata were cultured most frequently. Deep fungal infections occurred in many patients and were frequently observed late in the course of bacterial and viral infections. Ten patients had fungemia, and primary fungal pneumonia occurred in eight patients. Three patients had fungal infection of the central nervous system. Three of eight patients with fungal pneumonia and eight of ten patients with fungemia died as a result of their fungus infections. These patients frequently had poor renal function and were receiving high steroid doses or had recently been treated for kidney rejection. One patient with fungal pneumonia and six patients with fungemia had the fungus cultured from a superficial site. Several patients developed fungal infections late in the course of viral or bacterial infections. Amphotericin-B and 5-fluorocytosine remain the mainstays of antifungal therapy.
Human kidney tissue obtained at pretransplant nephrectomy from 13 adults and 1 child with end stage renal disease was cultured to provide a source for attempted detection of viruses. Cultures were observed throughout their life span for cytopathogenic viruses. Supernatants from 13 cultures were tested for hemagglutinating viruses (including measles, rubella, influenza, parainfluenza, and mumps) using various species of red blood cells. Kidney cells were cocultivated with Vero and human foreskin cells and indirect immunofluorescence was attempted in one instance. No viruses were detected. Nevertheless 9 of the 14 patients developed infections with herpes group viruses post-transplant. Either replicating viruses were not present in the kidneys of the patients prior to transplant or the techniques used were not adequate to detect them However, the establishment of organ cultures from patients with chronic renal disease is practical and may be a useful method for further virological investigation.
Cell-mediated immunity to murine cytomegalovirus (CMV) was tested by an in vitro lymphocyte proliferation assay. CMV antigen was prepared from infected mouse embryo fibroblasts by ultracentrifugation. Control antigen was prepared in a similar fashion from uninfected fibroblasts. Splenic lymphocytes from CMV-infected mice underwent significant proliferation when incubated with CMV antigen. Lymphocytes from uninfected mice did not proliferate when incubated in vitro with CMV antigen. The proliferation was shown to be specific, since lymphocytes from CMV-infected mice did not proliferate when incubated with control antigen or an indifferent (encephalomyocarditis) viral antigen. Lymphocyte proliferation was directly related to the number of lymphocytes in each culture and to the amount of viral antigen. However, at higher numbers of cells and with large amounts of viral antigen, the backgrounds increased, and the standard errors were larger. The optimal incubation time was eight days. Lymphocyte proliferation reached a maximum 15 days after CMV infection but was still significantly elevated above background 60 days later. This type of lymphocyte proliferation test with human lymphocytes and human CMV antigen can be used to study clinical questions regarding cell-mediated immunity to CMV in immunosuppressed patients, in children with congenital CMV, and in transplant patients after vaccination with attenuated CMV.