Biomedical subjects

T E Miller

Publications and source records attributed to T E Miller.

At least 127 records · Page 7Linked to original sources

PubMed1978

Rat liver nuclear skeleton and ribonucleoprotein complexes containing HnRNA.

Rat liver nuclei deprived of chromatin and nucleoplasm show a spongelike network which preserves its connection with nucleoli, the inner membrane of the nuclear envelope, and nuclear pore complexes. It contains all of the HnRNA, provided the endogenous proteolytic activity is inhibited by a proteolytic inhibitor such as phenylmethyl sulfonyl chloride (PMSC) or the fluoride form (PMSF). In the absence of these proteolytic inhibitors, HnRNA is dissociated from the spongelike network and sediments in a sucrose gradient as polydispersed ribonucleoprotein complexes. Furthermore, purified HnRNA as well as rRNA do not bind to the spongelike network when added to these nuclei. These observations demonstrate that the association of HnRNA to the nuclear skeleton is not an artifact. RNase treatment of the spongelike network digests the majority of the rapidly labeled RNA but does not alter the morphological aspect nor the architecture of this network. EDTA and heparin treatments affect neither the attachment of HnRNA nor the structural organization of this network. Electron microscope studies of the network reveal a characteristic flexuous configuration. Its relationship with diffused and condensed chromatin is discussed.

Animals↗

PubMed1978

Rat liver nuclear skeleton and small molecular weight RNA species.

Small molecular weight RNA species (smwRNAs) were studied in rat liver nuclei with and without chromatin as well as with and without nuclear envelope and nucleoplasm. From all the species identified, only two, N5 and 5Sb, were related to ribosomes. The others were localized exclusively in the nuclear skeleton or the spongelike network that was described in the preceding communication. This network or protein matrix contains a less abundant but exclusive set of molecules designated 5Sa, N1, and 4.5S, as well as other more abundant molecules which also exist in rat liver endoplasmic reticulum but not in polysomes or postribosomal RNP complexes. The smwRNAs behave like HnRNA; they remain located in the nuclear skeleton when nuclei are deprived of nucleoplasm and chromatin. With the information presently available, it is not possible to know whetherer both species are in the same or different RNP complexes and whether some of the smwRNAs contribute to the architecture of the nuclear skeleton. Distinct from any other nuclear RNA species, smwRNAs have two unique properties: facility of extraction, and resistance to nuclear ribonuclease digestion.

Animals↗

PubMed1978

Complement-mediated immune mechanisms in renal infection. II. Effect of decomplementation.

Animals were depleted of complement using cobra venom factor and the influence of complement depletion on the course of renal infection was studied. Complement depletion markedly increased the susceptibility of renal tissue to a challenge with an E. coli strain sensitive to the bactericidal activity of normal serum, but did not influence the outcome of a challenge with a serum-resistant strain of E. coli. These observations are consistent with the hypothesis that complement-mediated host immune mechanisms do play a role in the biology of renal infection and are an important component of the host's immune response in pyelonephritis.

Animals↗

PubMed1978

Complement-mediated immune mechanisms in renal infection.

The belief that the inactivation of complement by renal ammonia enhances the susceptibility of renal tissue to infection has been held for some years. This thesis has been investigated in the present experiments using cultures of renal tissue maintained in vitro under physiological conditions. The experiments have confirmed that exposure of normal serum to renal issue in culture does result in the rapid loss of complement activity, but that the inactivation was not due to renal ammonia. Furthermore, in quantitative experiments, the liver was found to have even greater anti-complementary activity than renal tissue. In experiments where the biological significance of this phenomenon was examined, it was shown that the bactericidal capacity of serum was maintained even after exposure to renal tissue. The results of these investigations suggest that the biological significance of the inactivation of complement by renal tissue in vitro has been over-emphasized and requires further studies in vivo.

Ammonia↗

PubMed1977

Legionnaires' disease: nickel levels.

Nickel concentrations in lung tissues of nine deceased Legionnaire victims average nine times that of controls. There is a significant correlation between the nickel levels in the lungs of the Legionnaire victims and the weights of the lung specimens. No similar correlation is evident in the study of the victims' kidney tissues or tissues from the controls.

Humans↗

PubMed1976

Diagnostic parameters in experimental renal infection.

Urinary tract infections are commonly encountered in medical practice but their laboratory diagnosis presents many difficulties. In this study we have used experimental models to assess the value of serum antibody, urinary antibody, rheumatoid factor, and the histochemical examination of renal tissue as diagnostic parameters. Under the conditions of the experiment the analyses did provide useful diagnostic information and may prove to be of value in the management of urinary tract infection in man.

Animals↗

PubMed1976

Experimental pyelonephritis: the effect of chronic active pyelonephritis on renal function.

In these experiments, renal function in chronic active pyelonephritis was investigated and the effect of antibiotic treatment and elimination of infection on the gross pathology, histopathology and renal function in animals with chronic pyelonephritis was determined. A severe loss of urine concentrating capacity was demonstrable when the maximum urinary osmolality of a group of animals with pyelonephritis was compared with control animals. Concentrating capacity decreased sharply over the first month but further loss over an eight-month period was minimal. A compensatory increase in the glomerular filtration rate (GFR) in the control, nonchallenged, group occurred after nephrectomy but no comparable compensation in the infected group was found. Antibiotic therapy had a marked effect on the urinary concentrating capacity and the defect in concentrating ability was significantly less in the treated animals during the first 30 days after challenge. Infection again prevented a compensatory increase in the GFR of pyelonephritic animals which was not reversed by antibiotic therapy. Blood urea concentrations in treated and nontreated animals were not significantly different nor did the eradication of infection affect the gross pathologic and histopathologic changes found at autopsy.

Animals↗

PubMed1976

Depression of the T-lymphocyte response to phytohaemagglutinin by renal cells.

The lymphocytic infiltrate in the renal parenchyma is a consistent histological feature of pyelonephritis, but the role of the lymphocytes in the immunobiology of pyelonephritis is not known. In this investigation the influence of the local environment on the potential function of T lymphocytes in the kidney was investigated. The experiments have demonstrated that the response of rat lymphocytes to stimulation in vitro with phytohaemagglutinin (PHA) can be entirely ablated by normal kidney cells. Even when the number of kidney cells added to cultures of lymphocytes was less than 2% of the cells present some ablation of T-lymphocyte function could be detected. The biological characteristics of the factor causing ablation of the PHA responsiveness of T lymphocytes were partially characterized and the factor appears to have unique features that differentiate it from lymphocyte chalones and other tissue factors influencing lymphocyte function. The results may explain recent findings where T lymphocytes were found to be the predominant lymphocyte in the inflammatory infiltrate but were not responsive to PHA in vitro.

Animals↗

PubMed1976

Bacterial interference as a factor in renal infection.

These experiments have investigated the role of bacterial interference as a determinant in the epidemiology of renal infection. Two unrelated strains of Escherichia coli, E. coli 08 and 075, isolated from cases of clinical pyelonephritis were used. Although both strains had identical morphology on conventional media they could be differentiated using genetically stable markers for streptomycin resistance and arabinose utilization. When the 2 strains of E. coli were introduced into the kidney simultaneously by direct inoculation mixed infections were readily established. On the other hand, although both strains of E. coli were equally invasive as individual pathogens, pyelonephritis, when induced using a retrograde challenge with a mixed culture of the same organisms was almost invariably caused by the 08 strain alone. Further experiments showed that bacterial interference occurred within the kidney and determined the pattern of infection. When unilateral renal infections were established with E. coli 08 and the animals subsequently challenged with E. coli 075, it was found that E. coli 075 infection never occurred in kidneys infected with E. coli 08 but infection was established in the contralateral kidney. The experiments have shown that mixed renal infection with E. coli are uncommon even when both pathogens are equally nephropathogenic and are introduced simultaneously into the bladder.

Animals↗

PubMed1976

Immunological enhancement in the pathogenesis of pyelonephritis.

The role of the immune response in pyelonephritis was investigated by manipulation of the host's immune capacity using the immunosuppressive drugs 6-mercaptopurine, cyclophosphamide and thiamphenicol. Treatment with 6-mercaptopurine depressed the humoral immune response but did not have an adverse effect on the course of renal infection. Thiamphenicol administration prevented the development of pathological lesions but this was due to the anti-bacterial activity of thiamphenicol and not to its immunosuppressive activity. Pyelonephritic animals treated with cyclophosphamide did not produce anti-bacterial antibody. Despite this, cyclophosphamide-treated animals were able to eliminate organisms more readily from the infected kidney than untreated animals with a normal humoral immune response. We believe that blocking of the phenomenon of immunological enhancement explains these unexpected results and that the immune response to renal infection may have an immunoenhancing role protecting the bacterial cell from otherwise effective host defence mechanisms.

Animals↗

PubMed1975

Antimicrobial resistance in urinary tract infections.

In this investigation Gram negative bacilli resistant to two or more antibiotics were isolated from 120 individuals with urinary tract infection. Antibiotic sensitivity patterns were determined by the Kirby-Bauer paper disc method and by an agar-plate-dilution method capable of measuring the minimum inhibitory concentration at the level of antibiotic attainable in the renal interstitium and urine. The results have shown that with selected antibiotics up to 75 percent of the isolates resistant by standard disc procedures are sensitive at concentrations of antibiotic readily attainable in the urine. The implications of these results in relation to the therapy of urinary tract infection have been discussed and evidence presented that the determination of the minimum inhibitory concentration of selected antibiotics may be of considerable value in the management of urinary tract infections.

Anti-Bacterial Agents↗

PubMed1975

Quantitation of immunoglobulin-bearing lymphocytes and the lymphocyte response to PHA in experimental pyelonephritis.

In these experiments the effect of experimental pyelonephritis on the distri-ution of B lymphocytes in the peripheral blood and lymphoid sites in the rat has been determined and the functional capacity of T cells during the course of infection has been investigated. The studies have shown that renal infection affects the distribution of lymphocytes and has a marked effect on the functional capacity of splenic T lymphocytes early in infection. Most of the lymphocytes forming the round cell infiltrate in the kidney have been identified as thymus-derived lymphocytes on their surface labelling characteristics. Evidence is presented to demonstrate the inability of T lymphocytes to function normally in the environment of the kdiney. It is suggested that ablation of cell-mediated immunity may be a factor contributing to the persistence of renal infection.

Animals↗

PubMed1975

Immunogenicity of Escherichia coli O antigen in upper urinary tract infection.

The role of immunogenicity of the infecting organism (Escherichia coli) in the antibody response to O antigen in upper urinary tract infection was investigated. Heat-killed vaccines were prepared from "immunogenic" organisms which had produced upper urinary tract infection associated with high titers of hemagglutinating antibody to O antigen and "nonimmunogenic" organisms which had produced upper urinary tract infection without a rise in antibody titer. "Immunogenic" 06 vaccine produced high titers of antibody in patients regarded as possibly "poor producers" of antibody, but "nonimmunogenic" 011 vaccine was not associated with a rise in titer in patients previously regarded as "good producers". These vaccines were significantly different in immunogenicity (P less than 0.05). Five vaccines were tested in 50 rats. The difference in hemagglutinating titers to O antigen between 06 and 011 was highly significant (P less than 0.001). Immunogenicity of the infecting organism appears to be a significant factor in determining antibody response to O antigen in upper tract infection.

Adult↗

PubMed1975

Acquiescent renal infection.

The relationship between bacterial infection of the renal parenchyma with Escherichia coli and the establishment of pathologic lesions has been investigate experimentally. Infection was established in one kidney and the bacteriologic, pathologic and immunologic features of infection were compared in the pyelonephritic and contralateral unmanipulated kidney. Whereas active bacterial infection was associated with pathologic changes in the pyelonephritic kidney, a poor correlation was found between bacterial growth and the gross pathology and histopathologic changes in the contralateral kidney. The conclusion from these studies is that infection of the kidney is not always associated with pathologic changes. The term "acquiescent infection" has been used to describe this host-parasite relationship in which active, persistent, bacterial infection is not associated with pathologic lesions. Evidence is presented that bacteria in the contralateral unmanipulated kidney are present in the renal parenchyma and that bacterial proliferation can be induced following renal trauma. Activation of infection and bacterial proliferation did not always result in histopathologic damage to the kidney and was not associated with an increase in serum antibody.

Animals↗

PubMed1975

Quantitation of potential T-lymphocyte function in rats.

A simple but dependable method for determining the functional capacity of thymus-derived lymphocytes is described. The in vitro culture conditions for determining the incorporation of tritiated thymidine after stimulation with phytohemagglutinin and other mitogens have been given in detail and the methodology confirmed by measuring the ablation of T-cell function in T cell depleted animals.

Animals↗

PubMed1975

Effects of bacterial lipopolysaccharide on the induction and expression of cell-mediated immunity. I. Depression of the afferent arc.

Bacterial lipopolysaccharide (LPS), being a B cell mitogen, enhances antibody production. When given prior to an injection of sheep red blood cells (SRBC) it caused a premature but not significantly increased production of antibody forming cells in regionally stimulated lymph nodes. There was a corresponding depression of T cell activity, as measured by the relative levels of delayed-type hypersensitivity (DTH) in normal and LPS-treated mice. Although LPS also induced hyperplasia of the reticuloendothelial system, and a consequent reduction in the effective antigenic dose of SRBC, this was not the reason for the reduced level of T cell activity. The opposing effects of LPS on T and B cell responses was due to premature inhibition of the T cell response by an accelerated production of antibody. This caused an earlier onset of the inhibitory mechanism which regulates the T cell response and is specific for the inducing antigen.

Animals↗

PubMed1975

Antitumor activity of bacterial infection. II. effect of Listeria monocytogenes on growth of a guinea pig hepatoma.

Growth of a guinea pig hepatoma was suppressed when tumor cells were mixed with viable Listeria monocytogenes (LM) before intradermal (id) injection into syngeneic recipients. Heat-killed LM were less effective than viable organisms in suppressing tumor growth. A vaccine containing oil droplets and LM cell walls lacked antitumor activity. Intratumor injection of viable LM on the 7th day after id injection of tumor cells prolonged survival of guinea pigs that did not succumb to LM infection. After intratumor injection of 0.6 times 10-8-1.0 times 10-8 LM, 5 of 22 guinea pigs died from acute infection (23 percent). In the 17 survivors, 3 tumors regressed completely (18 percent). Animals surviving injections of LM and tumor cells were immune to a second challenge with tumor cells. Immunization ofguinea pigs with an intravenous injection of LM decreased the mortality from intratumor injection of LM, but the intratumor injection of LM failed to cure a significant fraction of LM-immune animals bearing 7-day hepatoma transplants. BCG was more effective than LM in producing tumor regression. Synergism between LM and BCG was not observed, and simultaneous intratumor injection of BCG and LM was no more effective than intratumor injection of BCG alone in the treatment of 12-day tumor transplants.

Animals↗

PubMed1975

Antigen presentation as a factor in the protective immune response to renal infection.

Host protection against renal infection may be augmented by active immunization against the causative organism. In these experiments we have investigated the effect of varying amounts and methods of presentation of bacterial antigen on the seconday immune response. Primary immunization with varying amounts of both killed and live antigen did not affect the nature of the secondary immune response although active renal infection did have a noticeable effect on the titre of serum antibody during the primary immune response. The experiments confirmed the presence of immunological memory to the somatic antigen of E. coli and showed that memory persisted for at least 6 months after primary immunization. Experiments have also been carried out which have demonstrated that memory to the somatic antigen of E. coli is carried by the B lymphocyte.

Animals↗