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Biomedical subjects

R H Rubin

Publications and source records attributed to R H Rubin.

At least 163 records · Page 9Linked to original sources
PubMed1989

The in vivo and in vitro effects of interleukin-1 and tumor necrosis factor on murine cytomegalovirus infection.

The effects of tumor necrosis factor (TNF) and interleukin-1 (IL-1) on infection with murine cytomegalovirus (MCMV) were investigated in vitro and in vivo. The addition of each of these cytokines (at 1 ng/ml) to tissue culture monolayers 24 hr prior to MCMV challenge produced a reproducible decrease in vital titer (from 1 x 10(8) pfu to approximately 4 x 10(6) pfu for both cytokines). There was no further increase in this effect when a 10 or 100 ng/ml of each of these cytokines was employed. Despite these in vitro effects, the pretreatment of suckling, weanling, or adult mice with 80 or 400 ng of TNF or IL-1 alone, or 80 ng of each cytokine together, had no effect on the survival of mice following MCMV. Similarly, neither of these cytokines adversely influenced the protective effects of hyperimmune anti-MCMV antiserum; that is, they did not attenuate the protection conferred by the antiserum nor affect the protective effects of subtherapeutic doses of the antiserum. We conclude that despite promising antiviral effects against MCMV in vitro, these agents do not result in a useful therapeutic effect in vivo. Moreover, despite the ability of IL-1 to induce ACTH and corticosterone in mice, IL-1 treatment did not increase the mortality to CMV.

Adrenal Cortex Hormones↗
PubMed1989

Dietary marine lipid does not alter susceptibility of (NZBxNZW)F1 mice to pathogenic microorganisms.

Female (NZBxNZW)F1 mice were fed for one month with a diet in which the sources of fat were either melted beef tallow or fish oil, the latter regimen being associated with a marked decrease in the expression of auto-immune disease in these animals. To test whether or not this beneficial effect was associated with an increased risk of infection, animals fed each of these diets were challenged intraperitoneally with graded doses of four different classes of microorganisms: a gram positive bacillus that is an intracellular parasite (Listeria monocytogenes), an exotoxin-producing gram negative bacillus (Pseudomonas aeruginosa), a yeast (Candida albicans), and a herpes group virus (murine cytomegalovirus). There was no difference in the susceptibility of the animals fed the two different diets to any of these infections as shown by either determinations of the LD50 for each organism or by assessment of the times of survival for those animals that did succumb. We conclude that the beneficial anti-inflammatory effects of fish oil diets in these mice are not associated with an increased risk of infection with a variety of microbial agents.

Animals↗
PubMed1989

Invasive aspergillus infection: possible non-ward common source within the hospital environment.

Six immunocompromised patients housed in widely separated portions of a hospital campus developed invasive aspergillosis during a single month. This represented a significant increase (P less than .001) in the number of cases observed over the 3 years which included this event (19 cases in 36 months). Epidemiological investigation suggested that this cluster of cases was due to a common source outbreak related to construction activity in a central radiology suite serving the hospital. Such non-ward exposures to nosocomial hazards are becoming increasingly important for immunosuppressed hosts.

Adult↗
PubMed1989

Combined antibody and ganciclovir treatment of murine cytomegalovirus-infected normal and immunosuppressed BALB/c mice.

The efficacy of treatment with ganciclovir (DHPG) and antibody activity-containing ascitic fluid (AF) separately and in combination was studied in normal and immunosuppressed BALB/c mice challenged intraperitoneally with a lethal dose (10(6) PFU) of murine cytomegalovirus (CMV). With combination therapy, lower doses of both DHPG and AF were often as effective as a higher dose of either agent given singly. For instance, the survival rate of murine CMV-challenged immunosuppressed mice was doubled when 4 mg of DHPG per kg and a 1:16 dilution of AF were both administered in contrast to when each was used alone. In both groups of animals, combination therapy was shown to be more effective than either therapy individually, even when initiation of therapy was delayed as long as 48 h. Such an approach holds promise for decreasing the expense associated with antibody use and the dose-related toxicity associated with DHPG use while maintaining or possibly increasing the efficacy of prophylaxis and therapy of serious CMV disease in humans.

Animals↗
PubMed1989

Molecular epidemiology of adhesin and hemolysin virulence factors among uropathogenic Escherichia coli.

The pap, prs, pil, and hly operons of the pyelonephritic Escherichia coli isolate J96 code for the expression of P, F, and type 1 adhesins and the production of hemolysin, respectively; the afaI operon of the pyelonephritic E. coli KS52 encodes an X adhesin. Using different segments of these operons as probes, colony hybridizations were performed on 97 E. coli urinary tract and 40 fecal clinical isolates to determine (i) the presence in the infecting bacteria of nucleotide sequences related to virulence operons, and (ii) the phenotypic properties associated with such sequences. Coexpression of P and F adhesins encoded by pap-related sequences was detected more frequently among isolates from patients with pyelonephritis (32 of 49, 65%) than among those with cystitis (11 of 48, 23%; P less than 0.0001) or from fecal specimens (6 of 40, 15%; P less than 0.0001). Therefore, the expression of both adhesins appears to be critical in the colonization of the upper urinary tract. In contrast, afaI-related sequences were detected significantly more frequently among isolates from patients with cystitis, suggesting that this class of X adhesin may have a role in lower urinary tract infections. Urinary tract isolates differed from fecal isolates by a low incidence of type 1 adhesin expression among pil probe-positive isolates. hly-related sequences were only detected in pap probe-positive isolates. The frequency of hemolysin production among pap probe-positive isolates was not associated with a particular pattern of infection. The distribution of these virulence factors was similar in the presence or absence of reflux, indicating that structural abnormalities of the urinary tract did not facilitate colonization by adhesin-negative isolates.

Adhesins, Escherichia coli↗
PubMed1989

Structure and copy number of gene clusters related to the pap P-adhesin operon of uropathogenic Escherichia coli.

The structurally related pap and prs operons of the uropathogenic Escherichia coli isolate J96 encode a P and an F adhesin that mediate bacterial attachment to the human P blood group antigen and the Forssman antigen, respectively. Using probes prepared from different segments of the pap operon, Southern blot hybridizations were performed to characterize pap-related sequences of 30 E. coli clinical isolates expressing different adhesin phenotypes. Gene clusters encoding P and F adhesins displayed no restriction site polymorphism in sequences homologous to the papH, papC, and papD genes that encode proteins essential to the transport and polymerization of the subunits of the P-pilus adhesin. In contrast, pap-related genetic elements associated with a null phenotype either lacked homology to the papH, papC, and papD genes or displayed a restriction site polymorphism in this region. Sequences within and surrounding the J96 papG and prsG adhesin genes that determine the binding specificities to the P and F antigens, respectively, were not conserved. However, gene clusters encoding different binding specificities could not be distinguished based on such restriction site polymorphisms. The majority of clinical isolates had more than one copy of pap-related sequences that involved gene clusters similar to the J96 pap operon, as well as genetic elements that were related only to a part of this operon. The implications of this unexpected copy number polymorphism with respect to possible recombination events involving pap-related sequences are discussed.

Adhesins, Escherichia coli↗
PubMed1989

Autoradiographic method for quantitation of radiolabeled proteins in tissues using indium-111.

A quantitative autoradiographic method was developed to measure 111In-labeled proteins in extravascular tissues with a spatial resolution sufficient to associate these proteins with tissue morphology. A linear relationship between measured grain density and isotope concentration was demonstrated with uniformly-labeled standard sources of epoxy-embedded gelatin containing [111In]albumin; half-distance of spatial resolution was 0.6 micron. The technique was illustrated by measuring 24-hr accumulation of diethylenetriaminepentaacetic acid-coupled 111In-labeled human polyclonal IgG and human serum albumin (HSA) in a thigh infection model in the rat. Gamma camera images localized the infection and showed target-to-background ratios of 2.5 +/- 0.3 for IgG and 1.4 +/- 0.02 for human serum albumin (mean +/- s.d., n = 3). Using quantitative autoradiography, significantly higher average tissue concentrations were found in the infected thighs at 4 to 4.5% of the initial plasma concentrations as compared to 0.2 to 0.3% of initial plasma concentrations in the noninfected thigh (p less than 0.05); these radiolabeled proteins were not inflammatory cell associated and localized primarily within the edematous interstitial spaces of the infection.

Animals↗
PubMed1989

Infection: the new problems.

Although great strides have been made in clinical transplantation, infection remains a major problem. Critical to the understanding of the infectious disease problems of the present and the foreseeable future is the recognition that the risk of infection is largely related to the interaction of two factors: the net state of immunosuppression present and the epidemiologic exposures the individual patient encounters. It is now apparent that different immunosuppressive agents with comparable antirejection effects will have differing effects on infectious processes. This is perhaps best illustrated by comparing the effects of cyclosporin and antithymocyte globulin on a murine model of cytomegalovirus infection. Cyclosporin appears to have little ability to reactivate latent virus but has profound virus-promoting effects once replicating virus is present. In contrast, antithymocyte globulin has potent reactivating effects but little influence on replicating infection. Thus, the infectious disease problems observed will be affected by the timing, nature, dose, and duration of the various components of the immunosuppressive program. As far as epidemiologic exposures are concerned, there is increasing emphasis on nosocomial hazards, particularly those encountered at such common sites within the hospital as operating rooms and radiology suites. Viral infections remain the most important single infectious disease problem among transplant patients for the foreseeable future. Although immunoglobulin prophylaxis and ganciclovir therapy appear to hold promise for limiting the effects of cytomegalovirus infection, hepatitis virus infection remains a major issue. In addition, it is likely that HIV infection, particularly the clinical management of asymptomatic carriers of the virus, will have an increasing impact on clinical transplantation over the next decade.

Communicable Diseases↗
PubMed1989

Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: comparison with gallium-67 citrate and technetium-99m-labeled albumin.

The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with 125I or 111In was compared to that of [67Ga]citrate and [99mTc]albumin in rats with deep thigh inflammation due to Escherichia coli infection. Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection. As early as 3 hr postinjection, [111In]IgG showed greater accumulation at the lesion than [99mTc]HSA (p less than 0.01). Both [125I]IgG and [111In]IgG showed greater accumulation than [67Ga]citrate (p less than 0.01). At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of [67Ga]citrate or [99mTc]HSA (p less than 0.01). At all imaging times, [67Ga]citrate accumulation was surprisingly low. In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, [111In]IgG accumulation was similar to the results obtained with Escherichia coli. These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG.

Animals↗
PubMed1989

Radionuclide imaging of experimental atherosclerosis with nonspecific polyclonal immunoglobulin G.

The utility of nonspecific polyclonal IgG for external imaging of experimental atherosclerosis was tested in a series of rabbits after balloon catheter deendothelialization of the abdominal aorta. Following injection of 111In-IgG, 111In-Fc, or 111In-Fab serial images were recorded. In addition, several animals received 125I-low density lipoproteins [125I-LDL], or 125I human serum albumin [125I-HSA] as positive and negative controls. Forty-eight hours after injection of the radiolabeled proteins, the aortas were removed, divided into abdominal and thoracic regions, counted, and autoradiographed. The images acquired after injection of 111In-IgG and 111In-Fc, showed clear focal accumulation of radioactivity in the healing abdominal aorta. In contrast, the images obtained after injection of 111In-Fab did not show focal radionuclide accumulation. For 111In-IgG and 111In-Fc there were three to six times as many counts in the abdominal as in the thoracic aorta, while for 111In-Fab and 125I HSA, the abdominal and thoracic counts were nearly equal. The results suggest that radiolabeled IgG and Fc can be used to image experimental atherosclerosis.

Animals↗
PubMed1989

Utility of the indium 111-labeled human immunoglobulin G scan for the detection of focal vascular graft infection.

The ability to diagnose and localize vascular graft infections has been a major challenge. Recent studies in animal models and humans with focal bacterial infection have shown that radiolabeled, polyclonal, human immunoglobulin G accumulates at the site of inflammation and can serve as the basis for an imaging technique. This study investigated this new technique for the diagnosis and localization of vascular graft infections. Twenty-five patients with suspected vascular infections involving grafts (22), atherosclerotic aneurysms (2), and subclavian vein thrombophlebitis (1) were studied. Gamma camera images of the suspected area were obtained between 5 and 48 hours after intravenous administration of 1.5 to 2.0 mCi (56 to 74 mBq) of indium 111-labeled, human, polyclonal immunoglobulin G. Scan results were interpreted without clinical information about the patient and were subsequently correlated with surgical findings, other imaging modalities, and/or clinical follow-up. In 10 of 10 patients found to have positive scan results, localized infections were confirmed at the involved sites. In 14 of 15 patients whose scan results were interpreted as negative, no vascular infections were identified at follow-up. The patient with false-negative results and recurrent bacteremia from an aortoduodenal fistula was found to have a negative scan outcome at a time when his disease was quiescent. These data suggest that nonspecific, human, indium 111-labeled immunoglobulin G scanning can be a useful noninvasive means of localizing vascular infections.

Adult↗
PubMed1988

Escherichia coli-specific T lymphocytes in experimental pyelonephritis.

We have assessed the phenotype and specificity of infiltrating mononuclear cells in a model of unilateral ascending acute pyelonephritis induced in rats with nephritogenic Escherichia coli or Pseudomonas aeruginosa. Histologic examination showed a predominance of mononuclear cells in the interstitium at all periods examined (4, 8, 15, 21, and 25 days), although at 4 and 8 days neutrophils were also abundant. Most of the mononuclear cells had the morphologic appearance of large lymphocytes. Immunoperoxidase studies with mAb showed that most of the mononuclear cells were W3/25+; many were W3/13+ and a small proportion were OX8+. Many of the mononuclear cells were Ia+. T cells were propagated in IL-2-containing media from small fragments of renal tissue with pyelonephritic lesions. Most of the propagated cells were W3/25+; fewer than (10%) were OX8+ or Ia+. T cells propagated from kidneys infected with E. coli responded, in proliferation assays, to the infecting strain or other E. coli strains, but not to P. aeruginosa or enterococci. The response to non-p-pilus-bearing E. coli was as great or greater than to E. coli with adhesins. T cells derived from lesions induced by P. aeruginosa responded to the infecting organisms, but not to E. coli. The response to the infecting organism (E. coli or P. aeruginosa) was MHC restricted, as indicated by the requirement for syngeneic APC. The results show that large numbers of T lymphocytes, especially with the "helper/inducer" phenotype, accumulate in the lesions of acute pyelonephritis in rats. Among the infiltrating T lymphocytes are activated cells and cells with specific reactivity to the infecting bacteria (or related strains). The findings indicate that T lymphocytes play a role within the kidney in response to the invading bacteria.

Animals↗
PubMed1988

Combined kidney and pancreas transplantation in diabetics.

Kidney and pancreaticoduodenal transplantation were simultaneously performed in 12 insulin-dependent diabetic patients. These patients had advanced secondary complications, including blindness, vascular disease, and disabling neuropathy. Average posttransplant hospitalization and charges were 17.7 days and $42,780 compared with 11.2 days and $29,000 for patients who received renal allografts alone. Following transplantation, blood glucose and glycosylated hemoglobin A levels promptly returned to normal in all patients. Two patients subsequently died, one after five months of a cytomegalovirus infection and one after seven months of a ruptured bladder. After a mean of 11.6 months of follow-up, ten patients (83%) remained independent of insulin and dialysis. The success of pancreas transplantation in diabetics with advanced complications now approaches that of other organ allografts. It therefore appears reasonable to recommend transplantation for diabetics with less severe secondary complications, since these candidates are most likely to realize the potential benefits of long-term normoglycemia.

Adult↗
PubMed1988

The problem of human immunodeficiency virus (HIV) infection and transplantation.

The problem of human immunodeficiency virus (HIV) infection and that of the acquired immunodeficiency syndrome (AIDS) are becoming increasingly important in clinical transplantation. The epidemiologic characteristics of this infection are important factors in determining the impact of this infection on transplant patients: in particular, the presence of a transmissible virus in the blood, tissues, and body fluids of even asymptomatic individuals for prolonged periods; the role of lymphocyte activation in accelerating the pace and effects of HIV infection, with the transplant patient having more reasons for lymphocyte activation than other patient categories; and the possible contributions of immunosuppressive therapy to the course of HIV infection. Already, at least 20 cases of primary HIV infection conveyed by infected blood or allografts at the time of transplant have been noted; a similar number of transplants have been carried out in asymptomatic carriers of the virus. The initial impression is that the course of HIV infection in these patients is accelerated, but information is incomplete and an international registry for the study of this problem has been established.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Cure of hemophilia A by orthotopic liver transplantation.

A patient with hemophilia A and transfusion-associated end-stage chronic liver disease underwent orthotopic liver transplantation. He had no requirement for exogenous factor VIII replacement during the 27 mo he survived. Although his hemophilia was cured, he had antibodies to the human immunodeficiency virus; ultimately he died of complications arising from acquired immunodeficiency syndrome. Liver transplantation for cirrhotic hemophiliacs can free them of the need for antihemophilic-factor therapy; however, application of this approach may be limited by the high prevalence of human immunodeficiency virus infection in multitransfused hemophiliacs.

Adult↗
PubMed1988

Ciprofloxacin in management of urinary tract infection.

Ciprofloxacin is a new quinolone derivative which is particularly well adapted for the treatment of bacterial urinary tract infection. Virtually all uropathogens are susceptible, and the development of resistance is uncommon. Its pharmacokinetic characteristics reveal that effective concentrations of the drug are easily achieved with twice a day oral therapy in the blood, urine, kidneys, and prostate--even in advanced renal failure. The drug is well tolerated, even with prolonged courses of therapy. It will be particularly useful in the treatment of antibiotic-resistant, complicated, and/or prostatic infection.

Bacterial Infections↗
PubMed1988

Detection of acute inflammation with 111In-labeled nonspecific polyclonal IgG.

The detection of focal sites of inflammation is an integral part of the clinical evaluation of the febrile patient. When anatomically distinct abscesses are present, lesion detection can be accomplished by standard radiographic techniques, particularly in patients with normal anatomy. At the phlegmon stage, however, and in patients who have undergone surgery, these techniques are considerably less effective. While radionuclide methods, such as Gallium-67 (67Ga)-citrate and Indium-111 (111In)-labeled WBCs have been relatively successful for the detection of early inflammation, neither approach is ideal. In the course of studies addressing the use of specific organism-directed antibodies for imaging experimental infections in animals, we observed that nonspecific polyclonal immunoglobulin G (IgG) localized as well as specific antibodies. Preliminary experiments suggested that the Fc portion of IgG is necessary for effective inflammation localization. Since polyclonal IgG in gram quantities has been safely used for therapy in patients with immune deficiency states, we decided to test whether milligram quantities of radiolabeled IgG could image focal sites of inflammation in humans. Thus far, we have studied a series of 84 patients with suspected lesions in the abdomen, pelvis, vascular grafts, lungs, or bones/joints. In 48 of 52 patients with focal lesions detected by surgery, computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US), the IgG scan correctly localized the site, while 31 patients without focal inflammation had no abnormal focal localization of the radiopharmaceutical. Four patients had false negative scans and one patient had a false positive scan. For this small series, the overall sensitivity and specificity were 92% and 95%, respectively. In this report, we review our experience with this exciting new agent.

Acute Disease↗