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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 541 records · Page 30Linked to original sources
PubMed1984

Nonquaternary cholinesterase reactivators. 2. Alpha-heteroaromatic aldoximes and thiohydroximates as reactivators of ethyl methylphosphonyl-acetylcholinesterase in vitro.

We prepared six pairs of alpha-heteroaromatic aldoximes, RC(= NOH)H, and thiohydroximates, RC(= NOH)S-(CH2)2N(C2H5)2, where R represents various oxadiazole and thiadiazole rings. Each compound was characterized with respect to the following: structure, (hydroxyimino)methyl acid dissociation constant, nucleophilicity toward trigonal carbon and tetrahedral phosphorus, octanol-buffer partition coefficient, reversible inhibition of eel acetylcholinesterase (AChE), and in vitro reactivation of AChE inhibited by ethyl p-nitrophenyl methylphosphonate. Eight of the twelve compounds significantly reactivate ethyl methylphosphonyl-AChE, but inherent reactivities are moderate to low: the most potent nonquaternary reactivator, 3-phenyl-5-[(hydroxyimino)methyl]-1,2,4-oxadiazole, is 17 times less reactive than the well-known reactivator 2-[(hydroxyimino)methyl]-1-methylpyridinium iodide (2-PAM). One of the nonquaternary compounds, 3-phenyl-1,2,4-oxadiazole-5-thiohydroximic acid 2-(diethylamino)ethyl S-ester, is a powerful reversible inhibitor of AChE (I50 = 7.5 microM). The observed relationships between nonquaternary compound structure, reactivation potency, and anti-AChE activity reveal important molecular requirements for high reactivity toward phosphonylated AChE.

Binding Sites↗
PubMed1984

Structure-activity relationships for reactivators of organophosphorus-inhibited acetylcholinesterase: quaternary salts of 2-[(hydroxyimino)methyl]imidazole.

A series of 1,3-disubstituted-2-[(hydroxyimino)methyl]imidazolium halides were prepared and evaluated in vitro with respect to their ability to reactivate acetylcholinesterase inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-2-butyl methylphosphonofluoridate (GD). The compounds conform to the general formula N(CH3)C(CHNOH)N(CH2OR)CHCH+ X Cl-, where R = CH3, (CH2)3CH3, (CH2)7CH3, CH2C6H5, CH2C10H7, (CH2)3C6H5, CH(CH3)2, CH2C(CH3)3, and CH(CH3)C(CH3)3. For comparison we also evaluated three known pyridinium reactivators, 2-PAM, HI-6, and toxogonin. The imidazolium aldoximes exhibit oxime acid dissociation constants (pKa) in the range 7.9-8.1, bracketing the value of 8.0, believed to be optimal for acetylcholinesterase reactivation. With imidazolium compound in excess over inhibited enzyme, the kinetics of reactivation are well behaved for EPMP-inhibited AChE and depend on the nature of the alkyl ether group R. For GD-inhibited AChE, maximal reactivation was used to compare compounds because rapid phosphonyl enzyme dealkylation and enzyme reinhibition complicate interpretation of kinetic constants.

Acetylcholinesterase↗
PubMed1984

Nurse/patient dependency--a review of different approaches with particular reference to studies of the dependency of elderly patients.

The dependency of elderly patients is the outcome of interaction effects between the patient and his or her environment, and over a protracted stay in hospital, environmental factors can be as influential in determining a patient's dependency as the patient's medical or physical condition. Rigid institutional regimes and inadvertent reinforcement of dependent behaviours by nursing staff appear to play an important part in the development of institutionally induced dependency. Studies of patient dependency which assume that dependency arises largely from the physical or mental condition of the patient lack validity because the major source of variation in nursing activity is seen as an almost mechanistic response to patients' dependency. It is argued that, rather than patient dependency 'causing' nursing actions, nursing actions can cause patients to become more or less dependent.

Aged↗
PubMed1984

Elastic fibers in the anulus fibrosus of the dog intervertebral disc.

A light microscopic investigation of the anulus fibrosus in cervical intervertebral discs of the dog was conducted to ascertain the arrangement and distribution of elastic fibers. Elastic fibers were observed in all lamellae of the anulus fibrosus. However, collagenous fibers were the predominant type of connective tissue fiber, and elastic fibers were randomly dispersed among them. Intralamellar (collagenous and elastic) fibers were vertically and obliquely oriented in both superficial and deep lamellae of the anulus fibrosus. All intralamellar fibers were densely and regularly arranged in superficial lamellae, but they were more loosely organized in deep lamellae. A narrow border of interlamellar, elastic fibers was observed between broader, contiguous lamellae in the superficial zone of the anulus fibrosus. Interlamellar elastic fibers wer vertically and obliquely arranged in superficial lamellae; however, they were radially oriented in deep lamellae. The deepest lamella of the anulus fibrosus consisted of a loose, three-dimensional network of intermeshing collagenous and elastic fibers. These observations suggest that elastic fibers are integral components of the articular and shock absorption mechanisms of the anulus fibrosus, and the cervical intervertebral disc of the dog is a suitable model for experimental investigation of the role of elastic fibers in intervertebral disc herniation.

Animals↗
PubMed1984

The expressed T cell repertoire is hierarchical: the precise focus of lysozyme-specific T cell clones is dependent upon the structure of the immunogen.

The breadth of the expressed T cell repertoire to antigens under Ir gene regulation is central to the understanding of Ir gene function. While major histocompatibility complex (MHC)-related differences in the elicited T cell repertoire are readily demonstrated, the reasons for the choice of particular determinants are not clear. It is commonly assumed that the Ia molecules as the sole products of Ir genes somehow influence the choice of determinants selected for response. That this choice can be severely restricted in the C57BL/6 mice to hen egg-white lysozyme (HEL) was shown earlier with L2 (a.a. 13-105) immunization. L2, as the major cyanogen bromide cleavage fragment of HEL represents about 70% of the whole molecule and contains all the determinants recognize by proliferative T cells induced with HEL in this strain. All clones obtained from L2-immunized B6 mice recognized HEL and determinants available only within the T11 peptide (a.a. 74-96), suggesting that the entire T cell repertoire was restricted to determinants within the T11 region for HEL [1]. To test this hypothesis, long-term T cell lines were derived from HEL-immunized B6 mice. Bulk HEL- and L2-induced T cell lines showed similar L2-specific responses. However, in contrast to clones from the L2-lines, which were all specific for T11, the large majority of clones from the HEL-induced lines were specific for "non-T11" determinants. Antigen recognition of all clones was restricted by a similar restriction element on the I-Ab molecule. Thus, T cells directed against "non-T11" determinants available on the L2 fragment were not induced by L2 itself but required the whole molecule. The evidence clearly shows that within the T cell repertoire, the selection of clones is dramatically changed by the context in which the determinants are available. In fact, a hierarchy of T cells specific for T11 and "non-T11" determinants results. Structural differences between HEL and L2 lead to an inversion of this hierarchy. As both the HEL- and L2-induced lines were maintained and cloned under identical conditions, this appears to reflect the cellular interplay that occurs during the early in vivo selection period, rather than during the later in vitro activation and propagation of the lines and clones derived from them. The direct implications of these findings relate to interpretations of Ir gene phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Antigen-specific T helper clones in a nonresponder strain require augmentation for expression of helper activity. Evidence for a possible antigen presentation defect in B cells.

Hen egg-white lysozyme (HEL)-specific Thy-1+, Lyt-1+2- T cell lines and clones were derived from the nonresponder C57BL/6 strain. Although the antigen-specific proliferative response of these T cells in the presence of syngeneic irradiated spleen cells as a source of antigen-presenting cells (APC) was normal, the same cells were incapable of stimulating B cells to secrete antibody in vitro. This deficiency could, however, be corrected by the addition of an excess of normal T cells or a supernatant from concanavalin A-stimulated rat spleen cells. Alternatively, the use of highly cross-reactive ring-necked pheasant lysozyme in the cultures allowed expression of efficient help, ruling out any inherent deficiency in the T cells. The antibody response was specific and required MHC compatibility between the T lines and responding B cells. By using (H-2b X H-2d)F1 B cells and another H-2d-restricted HEL-specific T line, it was shown that only the H-2b-restricted T-B collaboration required exogenous factors, and the H-2d-restricted collaboration did not. Because both proliferative and helper responses are dependent upon MHC-restricted antigen presentation by macrophage-APC and B cells, respectively, these results suggest that the defect in the nonresponder H-2b-restricted T-B collaborative pathway may relate to the inability of B cells to adequately process and present HEL to clonal T cells.

Animals↗
PubMed1984

A limited region within hen egg-white lysozyme serves as the focus for a diversity of T cell clones.

The C57BL/6 (H-2b) mouse is a nonresponder to hen egg-white lysozyme (HEL) injected i.p., owing to a T suppressor cell-inducing determinant at the amino-terminal region. After immunization with a 93-amino acid fragment (a.a. 13-105) of HEL lacking this determinant, all clones from two independently derived C57BL/6 T cell lines were found to be specific for epitopes within a subregion of peptide 74-96. Three specificity patterns for the clones could be defined on the basis of cross-reactivities with only two other species variant lysozymes. Reactivities of all three specificity groups was consistent with the serine to threonine substitution at position 91, although reactivity of one of the groups could be affected by substitutions at position 84. The results confirm at the clonal level that even for distantly related antigens, only limited regions are recognized by T cells. They are consistent with the notion that specific sites on the antigen capable of interaction with Ia molecules lead to dominance of certain regions for T cell reactivity. Moreover, the diversity in specificity among clones suggests that the limiting feature of T cell responsiveness is not a lack of available T cells in the repertoire directed against a single antigenic site.

Animals↗
PubMed1984

The pharmacy computer system at The Ohio State University hospitals.

The pharmacy computer system designed, developed, and implemented at The Ohio State University Hospitals is described. The computer system was developed to make more efficient use of hospital facilities and professional staff time. The pharmacy system operates on the mainframe hospital system using computer terminals with light-pen and keyboard access. Current online applications include order entry, patient profiles, pharmacokinetic calculations, and preparation of unit dose cart fill lists. Batch processing functions include drug-use review, drug-drug interactions, and financial management reports. Approximately 95% of unit dose orders and 20% of i.v. orders are conditionally entered by pharmacy technicians for subsequent verification by pharmacists. The system saves considerable staff time in the i.v. admixture and billing areas and has relieved pharmacists from performing many clerical and repetitive tasks. Disadvantages of the system include (1) its dependence on another department for patient admission, transfer, and discharge information and (2) delays in obtaining approval for program modifications and new applications. The advantages of the pharmacy computer system lie in its ability to access information from other computerized databases in the hospital. Future modifications and enhancements to the system are discussed.

Computers↗
PubMed1984

Surgical staging in endometrial cancer: clinical-pathologic findings of a prospective study.

The pathologic features of a prospective study of FIGO stage I endometrial cancer is presented. The uterus, tubes, ovaries, and pelvic lymph nodes of 222 cases and aortic nodes of 157 cases have been analyzed. The surgical-pathologic specimen would suggest a negligible risk for lymph node metastasis if: cancer is confined to the endometrium irrespective of grade, invasion is superficial for grades 1 and 2 tumor, the intermediate third of the myometrium is invaded for grade 1 tumor only, and occult disease is not present in the cervix and/or adnexa. Conversely, a substantial risk for lymph node metastasis exists if the surgical-pathologic study identifies superficial myometrial invasion by grade 3 cancer, intermediate myometrial invasion by grade 2 or 3 cancer, deep myometrial invasion by cancer of any grade, vascular space involvement, and extension of tumor to the cervix and/or adnexa.

Adenocarcinoma↗
PubMed1984

The utility of serum gastrin levels in assessing the significance of low serum B12 levels.

Elevated levels of serum gastrin as a consequence of gastric achlorhydria are characteristic of clinical pernicious anemia. In a largely male hospitalized population with an average age of 64 years, 7.7% had low levels of serum B12 (less than 170 pg/mL); only 2.5% of these had frank pernicious anemia. In an attempt to separate a subgroup with low levels of serum B12 in whom pernicious anemia may later develop, their serum gastrin levels were determined. Twenty-two percent had high values and, of these, 70% had low B12 absorptions. In patients with low serum B12 levels, serum gastrin assays may be useful in determining those in whom clinical pernicious anemia seems likely to develop.

Anemia, Pernicious↗
PubMed1983

A polypeptide secreted by transformed cells that modulates human plasminogen activator production.

A diffusible factor produced and secreted by malignant murine cells was capable of inducing plasminogen activator production by normal diploid human fibroblasts. The factor's ability to induce plasminogen activator was insensitive to treatment with nucleases, but its activity was destroyed by digestion with proteases. It is proposed that such a factor would play a role in malignancy if it would recruit normal cells that were adjacent to transformed cells to produce plasminogen activator which could result in tumor-promoted proteolysis.

Animals↗
PubMed1983

Molecular conformation and packing in collagen fibrils.

New X-ray diffraction data have been collected from specimens of tendon collagen stained with phosphotungstic acid. Measurements of the positions of the Bragg reflections associated with the crystalline lattice provide, for the first time, a complete description of the unit cell. A strong band of intensity in the molecular transform associated with the pitch of the molecular helix can be identified and a detailed analysis of the intensities and positions of the Bragg reflections in this band has been carried out. The principal conclusions are that the portions of the collagen molecule that contribute to these reflections have a common direction; that they have a length very much less than that of a complete molecule; that the paths of the individual portions through the crystal are incompatible with a completely straight molecule, and that the molecule is therefore crimped. No evidence was obtained for a second series of Bragg reflections attributable to a second set of molecular portions linking the first set, and it is concluded that the linking set is more mobile and subject to positional variation from cell to cell. The most plausible explanation of our finding is that the first set corresponds to the portions of the molecules in the overlap zone and the second set to the portions in the gap zone. A detailed analysis of the Bragg reflections in the strong band of intensity associated with the pitch of the molecular helix has provided information about the relative azimuthal orientations and the lateral positions in the unit cell of the five molecular segments in the overlap zone. None of the existing models for fibril structure accounts satisfactorily for all the results obtained in the present studies and alternative models are developed and tested.

Animals↗