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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 595 records · Page 33Linked to original sources

Electron microscopy shows periodic structure in collagen fibril cross sections.

X-ray diffraction was used to monitor the effects of electron microscope fixation, staining, and embedding procedures on the preservation of the three-dimensional crystalline order in collagen fibrils of rat tail tendon. A procedure is described in which the characteristic 3.8-nm lateral spacing is preserved, with increased contrast, in the diffraction pattern of the embedded fiber. This spacing is correlated with the separation between the tangentially oriented equally spaced lines of density observed in electron microscope ultrathin fibril cross sections of the same material. Optical diffraction of electron micrographs gives an objective measure of the periodicity and suggests that the fibril is composed of concentrically oriented crystalline domains. These observations, when combined with a recent interpretation of the native x-ray diffraction data [Hulmes, D. J. S. & Miller, A. (1979) Nature (London) 282, 878-880] suggest a tentative model for the three-dimensional structure of collagen fibrils.

Animals↗

Moderator variables for the relationship between life change and disorders.

The correlation between life change events and occurrence of disorders was investigated with the use of moderator variable measures of Jungian types, health locus of control, and optimal stimulation level. One hundred and twenty-four graduate and undergraduate men and women at Oregon College of Education were Ss. The following levels of moderator variables produced significant correlations: Introvert, Thinking, Feeling, Judgment, rational functions, and external health locus of control. The suggested rationale for integrating these findings is that high correlations between life change events and occurrence of disorders result from low levels of awareness and limited choices, accompanied by high degrees of conditionability.

Adolescent↗

Sensory feedback for head control in cerebral palsy.

Five school-aged children with cerebral palsy were given an auditory feedback signal when their heads tilted past a predetermined angle. After three to seven individual sessions, all of the children were able to work in the classroom on regular school activities while using the sensory feedback to monitor and after head position. Over a period of nine weeks, all children improved their stabilizing skills of the head and neck when responding to the performance information. Three of the children were successful at self-monitoring for up to one hour while maintaining the head within the required zone at least 80 percent of the time. Inability of the other two children to do so was probably related to poorer motor control and possibly to a lack of independent work skills.

Acoustic Stimulation↗

The role of two noninvasive tests in deep venous thrombosis.

A prospective study was performed to evaluate the accuracy and usefulness of two noninvasive modalities, Doppler ultrasonography and segmental air plethysmography, in the detection of deep vein thrombosis. Over a two-year period, 211 limbs were studied among 167 patients, and the results were compared with venography. Doppler ultrasonography was found to be very accurate in detecting above-knee thrombi (sensitivity: 92.4%, specificity: 90.7%) while plethysmography was found to be much less accurate (sensitivity: 77.3%, specificity: 62.4%). The results were also assessed according to the mode of patient presentation. Doppler ultrasonography was found to be very useful in symptomatic out-patients, because of the lower incidence of calf thrombi, and less accurate in symptomatic inpatients and in high risk in-patients being screened. The clinical usefulness of noninvasive detection of venous thrombosis is discussed with regard to the incidence of disease and the site of thrombosis in different patient groups under study, and recommendations are made based on these results.

Evaluation Studies as Topic↗

Hematologic effects of cis-platinum-bleomycin therapy.

A prospective study of the hematologic findings in 19 patients receiving cis-platinum (C-P) bleomycin (B) for squamous cell carcinoma of the head and neck was performed. CP 3 mg/kg was given on day 1, B 15 mg/m2 on day 3 and then by continuous infusison from day 3 to 10. Hematocrits declined in all patients from a mean of 41.6 +/- 3.9 to 36.6 +/- 4.9 (p less than 0.001) with the nadir seen by 10 days, reticulocyte count was unchanged. In 1 patient marked hemolysis occurred over 10-day period associated with the appearance of irregular spherocytes on smear, a situation similar to the index case which initiated this study. 5 other patients had spherocytes. A significant lymphopenia in the absence of neutropenia and thrombocytopenia was also observed.

Adult↗

Sharing of an idiotypic marker by monoclonal antibodies specific for distinct regions of hen lysozyme.

Idiotypes have been defined serologically as variable-region markers present on unique subsets of antibody molecules. Most studies involving myeloma proteins and antibody responses in inbred mice have indicated that idiotypy is closely related to antigenic specificity. However, indirect evidence suggests that idiotypy can sometimes be dissociated from specificity. In the response to the small monomeric protein, hen egg-white lysozyme (HEL), previous results demonstrated that 70--95% of the anti-HEL antibody found in sera of primed and boosted mice is specific for a particular region of HEL and bears a predominant idiotype (IdX-HEL). In this report, hybridoma anti-HEL antibodies tested with well-characterized peptide fragments of HEL show that the IdX-HEL marker can be found on antibodies of completely distinct antigen specificities. Thus, a mode of recognition other than antigenic recognition probably plays a major role in the immune response to HEL.

Animals↗

Differential major histocompatibility complex-related activation of idiotypic suppressor T cells. Suppressor T cells cross-reactive to two distantly related lysozymes are not induced by one of them.

B10 (H-2b) mice are genetic nonresponders to hen egg-white lysozyme (HEL) and the distantly related human lysozyme (HUL). However, anti-HEL or anti-HUL primary antibody responses in vivo or in vitro can be obtained in B10 mice by immunization with the appropriate lysozyme coupled to erythrocytes. T cells able to suppress either anti-lysozyme plaque-forming cells (PFC) response are induced in B10 mice after immunization with HEL-complete Freund's adjuvant (CFA) or HUL-CFA. This cross-reactivity of HEL and HUL in the induction and the expression of suppressive activity is in marked contrast to their very low cross-reactivity at the PFC level. These results suggest that either HEL or HUL can stimulate a suppressor T cell which recognizes a particular epitope present on both lysozymes. Suppressor cells induced by HEL or HUL bear the same predominant idiotype found on the majority of anti-HEL antibodies, and on the small proportion of anti-HUL antibodies cross-reactive with HEL. B10.Q (H-2q) mice are responders in vivo to HEL-CFA, but not to HUL-CFA. In contrast to B10, HEL-CFA priming in B10.Q micr induces helper cells whereas HUL-CFA priming induces suppressor cells. These suppressor cells are cross-reactive with HEL and are fully able to suppress HEL-specific helper cells. The presence of HEL-specific suppressor cell precursors in B10.Q mice which are not activated by HEL, seems to implicate differential choice by the antigen presenting system as a basis for Ir gene control, rather than the absence of a regulatory cell type from the T cell repertoire.

Animals↗

Endometrial carcinoma: clinical-pathologic comparison of cases in postmenopausal women receiving and not receiving exogenous estrogens.

Clinical and pathologic findings were compared in 43 postmenopausal endometrial carcinoma patients who had received exogenous estrogens prior to diagnosis and 79 similar patients unexposed to estrogens. Estrogen non-users were more likely to manifest lower parity, later menopause, obesity, hypertension, and diabetes, all of which have been considered to be constitutional risk factors for the development of endometrial carcinoma. Although estrogen users and non-users had similar extent of disease as judged by clinical stage, there was a tendency to more myometrial invasion in hysterectomy specimens from non-users, as well as greater frequency of unfavorable histologic types and grades of tumor. At short-term follow-up, more recurrences occurred in non-users, and this tendency appeared to be independent of clinical stage, histologic type, histologic grade, or modality of treatment. The significance of these and other observation to the determination of the risk-benefit ratio for estrogen administration is discussed.

Age Factors↗

Research as an impetus to improved treatment.

The relation between psychiatric research and treatment remains a controversial subject. A psychopharmacological research program implemented in a state psychiatric hospital resulted in a significantly improved treatment milieu. Diagnosis, length of stay, amounts and types of medications administered, legal commitment status, seclusion and restraint time, etc, were targeted as variables with which to measure change in the milieu. The variables showed significant changes, ie, improvement during the research period, as compared with a control period. The research discipline created a more rigorous approach to diagnosis and treatment. This, in turn, created an improved treatment milieu in which the research protocols could be implemented more meaningfully.

Adolescent↗

Spirometric "abnormality" in a normal male reference population: further analysis of the 1971 Oregon survey.

Conventional criteria for spirometric impairment (FVC and FEV1 less than or equal to 79% predicted, FEF25-75 less than or equal to 74% predicted, FEV1/FVC less than or equal to 0.69 for most ages) were applied to 507 healthy nonsmoking male subjects in the 1971 Oregon survey. Frequency of air flow impairment was higher than expected for a normal population. Of all subjects, 17.8% had an "abnormal" FEF25-75% and 19.7% an "abnormal" FEV1/FVC. "Decreased" lung volumes were seen in older subjects; of those over 55 years of age, 8.8% had a reduced FVC and 11.8% a reduced FEV1. These rates in a normal population may be used as a rough baseline for making inferences about a population under study. Similar rates were found in a cross-sectional survey of nonsmoking males representative of the population of a large industrial state. The major reason for these high rates of "abnormal" spirometry lies in the conventional definitions of abnormality. Tables showing cut-off points for abnormal spirometric values based on a 95% confidence interval for adult males of all ages and heights permit an alternative method for classification as abnormal.

Adolescent↗

Epitope specificity of the T cell proliferative response to lysozyme: proliferative T cells react predominantly to different determinants from those recognized by B cells.

The fine specificity of murine B 10.A/SgSn (B 10.A) T cells reactive with hen egg-white lysozyme (HEL) has been studied through the use of reduced, carboxymethylated HEL, a set of peptides encompassing the entire molecule, and a set of variant lysozymes from other species. Cells were taken from the lymph nodes draining the site of immunization at the base of the tail, and were restimulated in vitro with immunogen or analogue to measure T cell reactivity. Unlike B cell reactivity, which we have shown to be mainly associated with an epitope preserved in the N-C peptide (residues 1--17, Cys6--Cys 127, 120--129) most T cell reactivity appears to be directed towards a limited number of determinants on cyanogen bromide cleavage fragment II of HEL (LII) (13--105). This was confirmed by a cell-dilution assay in which antigen-reactive units are measured; reactivity was highest to LII, intermediate to N-C, and low but significant to cyanogen bromide cleavage fragment III (LIII) (106--129). Furthermore, priming with LII is as effective as immunization with HEL and results in the same extensive cross-reactivities to variant lysozymes. Although LII reactivity predominates in the response to HEL, injection of LIII and N-C reveals sizeable reactivity to the homologous peptides and to HEL. By cross-stimulation studies, specific epitopes could be defined in certain regions of HEL. B 10.A is clearly responsive to the overlap between N-C and LII (residues 13--17), and to an epitope in the region 106--121, but is poorly responsive to the C-terminal portion (120--129). The response to 106--121 is characterized by an exquisite specificity in which as little as a single amino acid substitution (Asn for Gln) is recognized.

Animals↗

Ir-gene control of T cell proliferative responses: two distinct expressions of the genetically nonresponsive state.

Two distinct modes of unresponsiveness to hen egg-white lysozyme (HEL) have been demonstrated in the "nonresponder" C57BL/10 Sn (B 10) mouse strain at the level of T cell proliferation. The first is an apparent inability to respond to a peptide of HEL comprising 70% of the molecule, LII (amino acids 13--105, when HEL is used as immunogen. On its own, LII is capable of eliciting a strong response from B 10 draining lymph node cells, but this capacity is concealed when the whole molecule is used for immunization (by suppressor cell activity raised against another part of HEL, as described by Adorini et al., J.Exp. Med. 1979. 150: 293). In the B 10.A mouse, LII and HEL are equally immunogenic. The second is an actual failure, presumably unrelated to suppression, to contrive a response to particular determinants on HEL, demonstrated for certain epitopes on LII and LIII (amino acids 106--129). Such a failure to respond was maintained despite an increase in the immunizing dose of peptide to a molarity at which HEL itself could overcome Ir gene control. B 10 cells responding to a high dose of HEL, or to the immunogenic lysozyme from ring-neck pheasant, were also unable to respond to these epitopes. These deficits in responsiveness appear to be characteristic manifestations of the relevant haplotype of the major histocompatibility complex. They may not only reflect the balance between competing T cell subpopulations, but also the constraints of associative recognition that may underlie the presentation of particular antigenic specificities.

Animals↗

A subtype of the prototypic karyotype in acute myeloid leukemia t (8; 21) (q22; q22), del 9 (q13; q23).

Two patients with acute myeloid leukemia are described in whom G- and C-banding analysis of bone marrow cells revealed, besides the translocation t(8;21), an additional structural anomaly characterized by the deletion of bands q13 to q23 of one chromosome no. 9. Findings in the literature support the proposal that this constellation represents a hitherto unreported subtype of the prototypic karyotype in AML.

Adult↗