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Biomedical subjects

R L Miller

Publications and source records attributed to R L Miller.

At least 145 records · Page 8Linked to original sources

Antibodies to the Giardia lamblia double-stranded RNA virus major protein can block the viral infection.

The double-stranded RNA virus-like particles, found among several independent isolates and cloned strains of Giardia lamblia, have previously been reported to be spheres of 35 nm with a genome of 7 kilobase pairs and a major protein of 100 kDa. The virus is capable of infecting certain virus-free isolates of G. lamblia. Antisera raised in mice against the intact virus did not react with the double-stranded RNA, but reacted strongly with the 100 kDa protein in Western blots. Preincubation of the virus with antisera abolished viral infectivity, whereas the antisera against double-stranded RNA showed only a weak blocking effect. Inclusion of the antiviral sera in the cultures of virus-infected G. lamblia at 10(3)-fold dilution resulted in elimination of the virus from the protozoa. Apparently, the 100 kDa protein is necessary for the initiation of viral infection and possibly subsequent assembly or replication of viral progeny particles.

Animals↗

Toluidine blue staining for detection of oral premalignant lesions and carcinomas.

The discriminative value of toluidine blue vital staining for detecting oral premalignant lesions and carcinomas was tested in the hamster DMBA buccal pouch model. The stain technique was further tested for specificity using the turpentine liquid petrolatum (TLP) hamster cheek pouch model for hyperplasia. Although carcinomas frequently exhibited toluidine blue staining, a 27.8% false negative result was noted. Premalignant lesions (dysplasia and carcinoma in situ) seldom retained toluidine blue stain and yielded a histologically confirmed (95.2%) false negative result. DMBA induced papillomas yielded a 5% false positive result. The TLP model failed to produce either clinically or histologically evident hyperplastic/hyperkeratotic lesions.

9,10-Dimethyl-1,2-benzanthracene↗

Intrarenal kallikrein-kinin activity in acute renovascular hypertension in dogs.

The intrarenal kallikrein-kinin system was studied during the acute phase of renovascular hypertension induced by renal artery constriction and during teprotide inhibition of kininase II in the dog. Kallikrein-like activity measured by both kininogenase and esterolytic assays, was increased during renal artery constriction (p less than 0.5) and (p less than 0.01). The administration of teprotide resulted in a further increase of renal cortical kallikrein-like activity and inhibited kininase II activity (p less than 0.01). Following the inhibition of kininase II, the plasma concentration of kininogen was also significantly decreased (p less than 0.01). These results suggest that kininase II inhibition may increase levels of intrarenal and plasma kinins and that decreased degradation of kinin peptides may contribute significantly to the acute hypertensive effect of teprotide.

Animals↗

Clinical modulation of doxorubicin resistance by the calmodulin-inhibitor, trifluoperazine: a phase I/II trial.

Drug resistance to chemotherapy agents such as doxorubicin appears to be an important cause of therapeutic failure in cancer treatment. Based on preclinical information demonstrating that the phenothiazine calmodulin-inhibitor trifluoperazine can enhance retention and cytotoxicity of doxorubicin in resistant cells, a phase I/II trial of the combination was performed to determine the maximally tolerated dose (MTD) of trifluoperazine that could be administered with doxorubicin. Patients with intrinsic (no previous response) and acquired (previous response with relapse) doxorubicin resistance were eligible. Doxorubicin was administered as a 96-hour continuous infusion (60 mg/m2) on days 2 through 5. Trifluoperazine was administered in divided doses orally on days 1 through 6, with dose escalation from 20 to 100 mg/d. Thirty-six patients were evaluable. The MTD of trifluoperazine was 60 mg/d, with dose-limiting toxicity being extrapyramidal side effects. No alteration of doxorubicin toxicity was observed. Seven of the 36 patients responded (one complete response [CR], six partial responses [PR]), with seven of 21 patients having acquired resistance, and zero of 15 with intrinsic resistance demonstrating responses. Doxorubicin plasma levels were not affected by trifluoperazine, and the maximal trifluoperazine plasma levels achieved were 129.83 ng/mL. This trial demonstrates the combination of trifluoperazine and doxorubicin is well tolerated, and the schedule recommended for phase II trials is doxorubicin, 60 mg/m2 (continuous infusion) days 2 through 5, and trifluoperazine, 15 mg four times per day orally days 1 through 6. Continued investigation of this combination is indicated for patients with acquired doxorubicin resistance.

Adult↗

Age and visual search: expanding the useful field of view.

The useful field of view is defined as the visual area in which information can be acquired within one eye fixation. We studied visual search within this context and found a reduction in the size of the field as a function of age. This loss, however, was recovered partially with practice. Standard acuity and perimetric tests of visual field, although diagnostic of disease, underestimate the degree of difficulty experienced by visually healthy older adults in everyday activities requiring the use of peripheral vision. To aid in predicting such performance, a model incorporating the effects of distractors and secondary task demands was developed.

Adult↗

Antigiardial activity of guanine arabinoside. Mechanism studies.

Guanine arabinoside (araG) inhibited the in vitro growth of Giardia lamblia WB with an ED50 value of 4 microM. The inhibition was prevented completely by 2'-deoxyguanosine, prevented partially by guanine and guanosine, and not prevented by adenine, adenosine or 2'-deoxyadenosine. Extracts of G. lamblia grown in the presence of [8-3H]araG contained radiolabeled araGMP, araGDP and araGTP. The formation of araGTP during the exponential phase of cell growth increased with time and was dependent upon the araG concentration. AraG was incorporated into G. lamblia DNA in a time-dependent manner at a ratio of 1 araG for each 27 2'-deoxyguanosine residues. Short-term exposure of growing cultures to araG was inhibitory to DNA synthesis but not to RNA or protein synthesis. Over an extended period, synthesis of all three macromolecules was depressed. Attempts to measure araG phosphorylation by cell-free extracts of G. lamblia under a variety of nucleoside kinase and nucleoside phosphotransferase assay conditions were unsuccessful. In an attempt to understand further the action of araG, the metabolic pathways of guanine, guanosine and 2'-deoxyguanosine were delineated in detail. The presence of araG did not appear to cause any major alterations in the metabolism of these compounds; however, it was accompanied by a 3- to 4-fold increase in the endogenous pools of ATP and GTP.

Adenine↗

Trypanosoma cruzi adenine nucleoside phosphorylase. Purification and substrate specificity.

An adenine nucleoside phosphorylase has been partially purified from extracts of epimastigotes of the Peru strain of Trypanosoma cruzi, the causative agent of Chagas' disease. The purification procedure separated this enzyme from the three other nucleoside-cleaving enzymes found in extracts. The adenine nucleoside phosphorylase, which efficiently cleaved 5'-deoxy-5'-methylthioadenosine (MTA), had a particle weight of 68,000 and exhibited a broad pH optimum between pH 6 and 8. In addition to MTA, the purified enzyme cleaved and synthesized adenosine and 2'-deoxyadenosine with high efficiency. This contrasts to the enzyme from S-180 cells which has been reported to cleave adenosine poorly and not to cleave 2'-deoxyadenosine. Several observations suggested that the three substrates, MTA, adenosine and 2'-deoxyadenosine, use a common catalytic site: (a) all served as alternate-substrate inhibitors exhibiting mutually competitive inhibition with Ki values equivalent to their respective Km values, (b) 5'-chloroformycin A exhibited a competitive Ki value of 4 microM with each nucleoside substrate, and (c) the Km value of phosphate derived from initial velocity studies (180 +/- 20 microM) was independent of the nucleoside substrate. Substrate specificity studies in both the synthesis and cleavage direction indicated that the enzyme had a broad specificity for bases and nucleosides. For the synthesis of nucleosides, the enzyme demonstrated a preference for an amino group in the position equivalent to the 6 position of purine. Compounds containing a hydroxyl group in this position were not substrates. Although a hydrogen or methyl group could substitute for a 6-amino group, a marked decrease in substrate efficiency was observed with these compounds. Alterations in the purine ring led to decreases in the maximal velocity values as evidenced by the substrate or nonsubstrate properties of 1-, 3-, and 7-deazaadenine and 4-aminopyrazolo[3,4-d]pyrimidine. The Km values for 5-methylthioribose 1-phosphate, ribose 1-phosphate and 2'-deoxyribose 1-phosphate with adenine serving as acceptor were 21, 150 and 370 microM. For nucleoside cleavage, the T. cruzi enzyme catalyzed the phosphorolysis of a variety of 5'-substituted adenine-containing nucleosides including those possessing 5'-hydrogen-, hydroxyl-, halogeno-, alkylthio-, amino- and azido-moieties. Inclusion of an ionized group in the 5'-position, such as 5'-carboxy-5'-deoxyadenosine or AMP, precluded substrate activity. 3'-Deoxyadenosine, arabinosyladenine and alpha-adenosine did not serve as substrates.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine↗

Hospital pre-admission orientation and patient satisfaction.

The literature reflects the importance of communication and information in patient satisfaction with health related services. The present study examines the effect of a physician-delivered orientation on patient satisfaction for a hospital stay of three days or less. A comparative study design was utilized. Patient satisfaction was increased when an orientation was provided prior to the hospital admission. The study found that when patients were provided an orientation, satisfaction with services improved, as did the perception of the physician's professionalism.

Communication↗

Naloxone inhibits mating and conditioned place preference for an estrous female in male rats soon after castration.

Three experiments were conducted to assess the role of endogenous opioids in controlling mating behavior and sexual reward in the male rat. In Experiment 1 SC administration of naloxone (0.5, 1.0, 5.0, or 10.0 mg/kg) significantly reduced mounting and ejaculation in male rats tested 14, but not 7 days, after castration. In Experiment 2 naloxone (5.0 mg/kg) administered SC to gonadally intact males, which had ejaculated repeatedly with one female until they were sexually sated, significantly inhibited the resumption of mating after the reintroduction of a female partner. One interpretation of these results is that naloxone attenuated the reward experienced by castrated and sexually sated males in the presence of an estrous female, thereby disrupting males' coital performance. This hypothesis was tested in Experiment 3 using a conditioned place preference paradigm in which males copulated with an estrous female in an initially "non-preferred" (white) compartment, whereas on alternate days they remained alone in an initially "preferred" (black) compartment. After 10 such conditioning sessions, males were either castrated or sham-operated. They later were given free access to both compartments in the absence of an estrous female. Seven days after conditioning and surgery, sham-operated, naloxone-injected males and both groups of castrates spent significantly less time than sham-operated, saline-injected controls in the initially "non-preferred" compartment. Fourteen days after conditioning and surgery castrated, naloxone-treated males spent significantly less time in the "non-preferred" compartment than males in the other three groups. Endogenous opioids may play an important role in the interpretation by males of the incentive motivational stimuli which emanate from an estrous female.

Animals↗

Clinical and histologic features of pityriasis lichenoides et varioliformis acuta in children.

Pityriasis lichenoides et varioliformis acuta (PLEVA) is commonly thought of as a disease of young adults, yet we identified five cases, involving patients who were 3, 5, 6, 8, and 11 years of age, among 13,000 consecutive specimens submitted to a general dermatopathology laboratory during a 15-week period. The clinical and histologic features of PLEVA in our cases were similar to those reported for adults, except that no lesions were observed on the scalp or mucous membranes of children. A high index of suspicion and biopsy specimens of suspected lesions are often needed to differentiate PLEVA from other papular and crusted eruptions seen in the pediatric age group. These include reactions to arthropods, Gianotti-Crosti syndrome, varicella, and erythema multiforme. Histologically, papular eczema and pityriasis rosea may be misdiagnosed as PLEVA.

Acute Disease↗

Erdheim-Chester disease. Case report and review of the literature.

Erdheim-Chester disease is a distinctive pathologic and radiographic entity characterized by bilateral, symmetric sclerosis of the metaphyseal regions of long bones and infiltration of foamy, lipid-laden histiocytes. Clinically, it ranges from an asymptomatic, focal process to a fatal, systemic disease. All previously reported cases of Erdheim-Chester disease are reviewed and a new case with diabetes insipidus, partial hypopituitarism, histiocytic skin lesions, and retro-orbital tumors is presented. An 11-year follow-up reveals progression from a benign, limited process to a progressive, systemic disease. Patients with Erdheim-Chester disease show markedly disparate clinical courses and some features similar to Hand-Schüller-Christian disease. They need careful monitoring and further attempts at treatment.

Adult↗

Idiopathic resorption of teeth. A report of three cases.

External resorption of teeth is a condition typically associated with etiologic factors within the adjacent alveolar bone, such as chronic periapical or periodontal infections, neoplasms, erupting permanent teeth, orthodontic movement, or trauma to the jaws. When none of these causes are present, resorption of teeth at the cementoenamel junction has been termed "idiopathic resorption of teeth." Three cases of idiopathic resorption of teeth are reported, the literature on previous cases is reviewed, and hypotheses as to causes and a new theory are postulated regarding the possible mechanism for osteoclastic resorption of teeth.

Adult↗