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Biomedical subjects

T E Miller

Publications and source records attributed to T E Miller.

At least 19 recordsLinked to original sources
PubMed1992

Isolation, expression, and mutation of a rabbit skeletal muscle cDNA clone for troponin I. The role of the NH2 terminus of fast skeletal muscle troponin I in its biological activity.

A cDNA for rabbit fast skeletal muscle troponin I (TnI) was isolated and sequenced. The clone contains a coding sequence predicting a 182-amino-acid protein with a molecular mass of 21,162 daltons. The translated sequence is different from that reported by Wilkinson and Grand (Wilkinson, J. M., and Grand, R. J. A. (1978) Nature 271, 31-35) in that Arg-153, Asp-154, and Leu-155 must be inserted into their original sequence. Amino acid sequencing of adult rabbit TnI confirmed this result. In order to investigate the role of the NH2 terminus of TnI in its biological activity, we have expressed a recombinant deletion mutant (TnId57), which lacks residues 1-57, in a bacterial expression system. Both wild type TnI (WTnI) and TnId57 inhibited acto-S1-ATPase activity and this inhibition could be fully reversed by troponin C (TnC) in the presence of Ca2+. Additionally both WTnI and TnId57 bound to an actin affinity column. Thus, both inhibitory actin binding and Ca(2+)-dependent neutralization by TnC were retained in TnId57. TnC affinity chromatography was used to compare the binding of TnI and TnId57 to TnC. Using this method, two types of interaction between TnC and TnI were observed: 1) one which is metal independent (or structural) and 2) one dependent on Ca2+ or Mg2+ binding to the Ca(2+)-Mg2+ sites of TnC. The same experiments with TnId57 demonstrated that the type 1 interaction was weakened, and type 2 binding was lost. This method also revealed an interaction between TnC and TnI which is dependent upon Ca2+ binding to the Ca(2+)-specific sites of TnC and which is retained in TnId57. Taken together, these results suggest that the NH2 terminus of TnI may constitute a Ca(2+)-Mg(2+)-dependent interaction site between TnC and TnI and play, in part, a structural role in maintaining the stability of the troponin complex while the COOH terminus of TnI contains a Ca(2+)-specific site-dependent interaction site for TnC as well as the previously demonstrated Ca(2+)-sensitive inhibitory and actin binding activities.

Actins↗
PubMed1992

Detection of nuclear matrix proteins in serum from cancer patients.

Morphological characteristics of the cell nucleus have long been used by pathologists in the clinical diagnosis of cancer. The nuclear matrix of the cell, the structure that serves to organize the chromatin within the nucleus, is known to reflect these morphological characteristics with regard to cell and cancer type. Monoclonal antibodies were developed to extracted nuclear matrix proteins. These antibodies were used in two-site immunometric assays to detect soluble nuclear matrix proteins in the supernatants of two dying cell lines and 15 tumor tissues. Furthermore, nuclear matrix proteins were detected at elevated levels in the sera of cancer patients compared with normal patient sera. In one assay, 63.2% of cancer sera read above 95% of normal sera, and in another assay, 73.7% of cancer sera read above 95% of the normal sera. With the development of monoclonal antibodies with greater cancer specificity, the detection of circulating nuclear matrix proteins may become an important clinical tool in the diagnosis and monitoring of cancer.

Animals↗
PubMed1992

A low molecular weight component derived from the milk of hyperimmunised cows suppresses inflammation by inhibiting neutrophil emigration.

An earlier study demonstrated that hyperimmunisation of dairy cows with a polyvalent bacterial vaccine stimulated the secretion of a small molecular weight anti-inflammatory moiety in the milk. This hyperimmune milk factor (HIMF) has been further investigated in the present experiments. HIMF was found to suppress the cellular phase of the response to carrageenin and also the neutrophil-dependent reverse passive Arthus reaction. These results, together with the observation that the administration of HIMF led to an increase in the number of circulating neutrophils, suggested that the agent might inhibit inflammation by interfering with the ability of neutrophils to emigrate from the vasculature. In vivo studies carried out to evaluate this possibility demonstrated that HIMF suppressed neutrophil emigration by up to 75%. In vitro experiments established that the ability of neutrophils to respond to chemotactic stimuli or adhere to endothelial cells was not affected by HIMF. It is possible, therefore, that the agent modulates inflammation by down-regulating the synthesis of inducible pro-inflammatory cytokines or adhesion molecules. Attempts are presently being made to isolate the active moiety to allow the activity of the agent at the molecular level to be studied in more detail.

Animals↗
PubMed1992

Suppression of inflammation by cyclosporin A is mediated via a T lymphocyte-independent process.

An athymic mutant rat strain was used to examine the hypothesis that modification of diseases with an inflammatory component by cyclosporin A (CsA) results from the suppression of nonspecific inflammatory mechanisms, rather than T-lymphocyte function, as is commonly inferred. Confirmation that the animal host was grossly depleted of T cells was obtained from anatomic and morphologic examination and functional tests of T-lymphocyte responsiveness. The experimental approach was to determine the effect of CsA on the course of experimentally induced infection with Escherichia coli, and extracellular pathogen. Host protection against this microorganism is dependent on an effective nonspecific inflammatory response. CsA administration prior to bacterial challenge resulted in a highly significant increase in bacterial numbers in the kidneys of both euthymic and athymic hosts. The data have provided a direct demonstration that modulation of the nonspecific inflammatory response by CsA can occur via a T lymphocyte-independent process.

Animals↗
PubMed1992

The pathobiology of subclinical pyelonephritis--an experimental evaluation.

Clinical studies have demonstrated a poor correlation between localization tests, which are designed to determine the site of urinary tract infection, and symptoms of upper urinary tract infection. One explanation is that microorganisms may be present in the kidney but not initiate an inflammatory response with associated symptoms. An animal model has been developed to obtain quantitative information on the comparative pathobiology of lesion-inducing and non-lesion-inducing infections. In this model, non-manipulated kidneys had acquired a persistent microbial flora within 48 hours of the lower urinary tract becoming infected. This bacterial invasion was not associated with gross or histologic changes within the renal parenchyma, but minor foci of inflammatory cells were seen beneath the epithelium lining the calyces. Ureteric urines from such kidneys contained many leukocytes and high numbers of bacteria. These results showed that the kidneys were infected, rather than colonized, and the term "subclinical" infection was appropriate. Antimicrobial agents were variably successful at eradicating the infection. These experimental observations support the concept of subclinical pyelonephritis and may explain the absence of symptoms in the clinically equivalent situation in humans.

Animals↗
PubMed1992

An experimental evaluation of the pharmacokinetics of fusidic acid in peritoneal dialysis.

Fusidic acid, an antimicrobial agent with activity against coagulase-positive and coagulase-negative staphylococci, has considerable potential for the management of staphylococcal peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Whether fusidic acid reaches therapeutic levels in the dialysate once therapeutic serum levels have been achieved is not known. An animal model of CAPD that reproduced essential features of the clinical procedure was used to investigate this issue. Although oral administration was the preferred route, fusidic acid is not absorbed from the gastrointestinal tract of laboratory rats, and a subcutaneous injection of diethanolamine fusidate was used to achieve serum levels of the agent equivalent to those achieved clinically in man. In this model, fusidic acid concentrations up to 28 times the MIC for staphylococci were found in the dialysate when therapeutic levels of the agent were reached in the serum. The data provide support for continued experimental and clinical evaluation of the role of fusidic acid in CAPD-associated peritonitis.

Administration, Oral↗
PubMed1992

Characterization of an animal model of continuous peritoneal dialysis in chronic renal impairment.

In this study we describe the successful development of a method of continuous ambulatory peritoneal dialysis in a rat with stable chronic uremia. The procedure involved the insertion of a permanent indwelling cannula into the peritoneal cavity through which a draining catheter was passed for each dialysis. Dialysis of uremic animal hosts over a 24-hour period removed 31% of the urea excreted in the urine by normal animals over the same interval. The effect of daily dialysis for 21 days on biochemical, hematologic and cytologic parameters was also determined. The model will allow the basic pathobiology of common problems such as CAPD-associated peritonitis to be investigated.

Animals↗
PubMed1991

The anti-inflammatory activity of a low molecular weight component derived from the milk of hyperimmunized cows.

"Immune" milk has been utilized as a source of biologically active compounds for many years. In the present study, a low molecular weight fraction, isolated from the milk of dairy cows hyperimmunized with a multivalent bacterial vaccine (HIMF), has been evaluated for anti-inflammatory activity. Analysis was carried out using the rat hind-paw oedema assay. HIMF was shown to have a marked anti-inflammatory effect in this model and carrageenin-induced oedema was suppressed by up to 80% in individual experiments. The agent was active following oral, subcutaneous, intramuscular, intraperitoneal or intravenous administration. Intravenous injection was particularly effective and amounts as small as 1 mg significantly reduced the inflammatory response to carrageenin. The experiments have established that milk from hyperimmunized cows contains a highly active anti-inflammatory compound and form a basis for further studies, which will attempt to isolate and further characterize the active moiety.

Animals↗
PubMed1991

Assessment of antiinflammatory agents using 125I-labeled human serum albumin to quantify footpad edema volume in the rat.

Intravenously injected human serum albumin, labeled with radioactive iodine ([125I]HSA), accumulates at inflammatory foci in proportion to the volume of the exudate, making it possible to quantify the volume of edema. This paper describes the use of [125I]HSA to measure edema formation in the carrageenin rat-footpad model, both continuously and at a single time point. In assessing antiinflammatory agents, the method was shown to be more sensitive than the most commonly used technique of thickness measurement. Because anesthetics are known to suppress inflammation, the comparative effect of five anesthetic agents on the inflammatory response was determined. Ether was the only anesthetic tested that did not substantially inhibit the accumulation of edema. The technique overcomes many of the limitations of previously used procedures and has the potential to become the method of choice when assessing edema in the rat footpad.

Anesthetics↗
PubMed1991

An empirical evaluation of the performance of antibody identification tasks.

Four empirical studies were conducted for better understanding of the nature of problem-solving activities by medical technologists and medical technology students when performing antibody identification tasks. The results indicated the importance of strategies that ensure the collection of converging evidence, as these strategies protect against the fallibility of commonly used heuristics and against errors due to simple slips. The results also indicate that not only do students make significant numbers of errors, but so do practicing technologists. In one of the studies covering a 1-year period, for instance, a group of 16 technologists made a total of 41 errors in 1057 cases. On the basis of these findings, several alternatives are proposed to reduce errors.

Adult↗
PubMed1991

Pharmacokinetics of fusidic acid in laboratory animals.

The ability of evaluate the efficacy of fusidic acid in animal models of infectious disease is limited by the absence of pharmacokinetic data for the agent in laboratory animals. In our study, aspects of fusidic acid pharmacokinetics were compared in rats (Rattus norwegicus), mice (Mus musculus), rabbits (Oryctolagus cuniculus), and guinea pigs (Cavia porcellus). Sodium fusidate was poorly absorbed after oral administration to rats, although limited absorption occurred in guinea pigs, mice, and rabbits. Subcutaneous injections of diethanolamine fusidate to laboratory rats, however, achieved a serum profile similar to that observed in humans. There was no evidence of drug accumulation in rats given repeated subcutaneous doses of diethanolamine fusidate during a 4-day period, but rabbits showed clear evidence of a cumulative effect.

Animals↗
PubMed1991

Thielemann's diagonal law of occlusion revisited.

Thielemann's studies of malocclusal relationships and the frequently observed chain reactions created in distant localities led to the formulation of a philosophical approach to occlusion that is also of practical premeditative clinical relevance for the practitioner. Dr. Thielemann presumed to name it a law, and repeated clinical observations apparently support and reinforce his claim. All disciplines of dentistry inevitably encounter and need to know about this aspect of fission-reactive involvement with the common and seemingly innocuous malocclusions. By incorporating the law into the diagnostic, planning, corrective, and therapeutic stages of treatment, the clinician can readily categorize patients for needs assessments and future goals in treatment.

Adult↗
PubMed1991

Comparison of the results of a standardized AIDS prevention program in three geographic locations.

A standardized AIDS prevention program, Stop AIDS, was tested with gay and bisexual men in 3 different geographic locations: metropolitan Chicago; Orange County, California; and Phoenix, Arizona, employing a test of AIDS knowledge, attitudes, and behavior. Results indicted that the Chicago participants began with the most knowledge about AIDS but gained least in the workshop, ending lowest, while the Orange County participants started with the least knowledge and gained the most, ending highest. The same change pattern was demonstrated in terms of attitudes. However, all groups started the discussion group with approximately the same risk behavior for HIV transmission, and all groups committed to the same amount of change in risk behavior at workshop termination, demonstrating the independence of behavior change from knowledge and attitude changes. Additionally, all 3 groups had the same 8 of 15 significant correlations of measures with no correlation between knowledge about AIDS, attitudes toward AIDS, and post-workshop intentions regarding risk behavior. These results indicate that Stop AIDS is an effective prevention program in all 3 locations, but that this and other programs should emphasize actual risk-behavior change rather than knowledge increase or healthier attitudes to produce the greatest lethality reduction.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Ureteric catheterization in the diagnosis of pyelonephritis--an experimental evaluation.

Experimental models of renal infections have been used to determine the accuracy with which the cellular and microbiologic components of ureteric and voided urine reflected the pathologic status of the kidney in pyelonephritis. In acute pyelonephritis, the composition of the ureteric urine reflected the pathologic status of the kidney, although in a few cases ureteric samples were either sterile or cell free. Animals with chronic pyelonephritis in which the lesions were either infected or sterile commonly had sterile ureteric urine. Pyuria, however, was demonstrable in both these situations. In subclinical pyelonephritis, ureteric samples from infected kidneys were variably culture positive, although pyuria was a common observation. Discriminate function analysis based on actual renal status and ureteric data gave an overall correct classification rate of 67% and demonstrated at least 80% agreement in four of the five classification groups.

Animals↗
PubMed1990

Cyclosporin A modulation of the acute inflammatory response: an explanation for the effect of CsA on host defences in infection.

Previous studies have shown that the administration of cyclosporin A (CsA) to animals with experimentally induced pyelonephritis resulted in considerable exacerbation of infection. T-lymphocytes are not involved in the host response to pyelonephritis but neutrophils are known to be a key component in the pathogenesis of this infection, so the effect of CsA on this inflammatory component was investigated. CsA administration did not affect the metabolic activity of neutrophils in vitro nor their ability to phagocytose and kill microorganisms. However, the ability of neutrophils to mobilize to a sterile inflammatory focus in vivo was significantly impaired. Further experiments, using models of pyelonephritis and subcutaneous infection, demonstrated that the CsA-induced suppression of neutrophil mobilization was directly related to the observed increase in bacterial numbers and exacerbation of tissue damage. Additionally, the actual effect of CsA on host defences and the outcome of infection was found to be dependent on the level of the initial infectious challenge. The results of this study provide an explanation for the current pattern of infectious disease in patients treated with CsA, in whom infection with extracellular pathogens is still common. It is also clear that the effect of CsA on inflammatory mechanisms may explain the efficacy of the agent in inflammatory diseases such as rheumatoid arthritis. This suggests a wider therapeutic role for CsA than is currently recognized.

Acute-Phase Reaction↗
PubMed1990

Changes in knowledge, attitudes, and behavior as a result of a community-based AIDS prevention program.

The study evaluates the outcome of a California-based AIDS prevention program, "Stop AIDS." Community discussion groups focusing on information, attitudes, and behavior associated with HIV infection and transmission were conducted in one-time, 3 1/2-hour sessions. Participants completed different versions of the AIDS Prevention Test before and after the discussion group. Significant positive shifts in information, attitudes, and behavior were observed as a function of the discussion group participation. Whereas pretest knowledge correlated with pretest behavior and posttest knowledge, only pretest behavior correlated with the crucial variable of posttest intended behavior. When changes from pretest to posttest were analyzed, both information and attitude change correlated to changes in behavior. The intervention and evaluation procedures are proposed as a replicable national model for community-based AIDS prevention programs.

Acquired Immunodeficiency Syndrome↗