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Biomedical subjects

L S Miller

Publications and source records attributed to L S Miller.

At least 109 records · Page 6Linked to original sources
PubMed1987

Antidepressant and circadian phase-shifting effects of light.

Bright light can suppress nighttime melatonin production in humans, but ordinary indoor light does not have this effect. This finding suggested that bright light may have other chronobiologic effects in humans as well. Eight patients who regularly became depressed in the winter (as day length shortens) significantly improved after 1 week of exposure to bright light in the morning (but not after 1 week of bright light in the evening). The antidepressant response to morning light was accompanied by an advance (shift to an earlier time) in the onset of nighttime melatonin production. These results suggest that timing may be critical for the antidepressant effects of bright light.

Circadian Rhythm↗
PubMed1987

Studies on the cellular localization and distribution of glucocorticoid receptor and estrogen receptor immunoreactivity in the central nervous system of the rat and their relationship to the monoaminergic and peptidergic neurons of the brain.

By means of monoclonal antibodies against the rat liver glucocorticoid receptor (GR) and the human estrogen receptor (ER), in combination with an immunocytochemical analysis, it has been possible to map out GR and ER immunoreactive (IR) neurons in the rat central nervous system and GR IR glial cells in the white matter. The GR IR is located in the cytoplasm and especially in the nucleus while the ER IR is only demonstrated in the nuclei of the neurons. Upon adrenalectomy the GR IR appears to be present exclusively in the cytoplasm, while after castration the ER IR is still exclusively present in the nuclei. Upon corticosterone treatment of the adrenalectomized rat the GR IR is again predominantly found in the nuclei of the neurons. These results indicate that the occupied GR and the unoccupied and occupied ER are located in the nuclei and the unoccupied GR in the cytoplasm. Evidence has been presented that large numbers of monoamine and peptide nerve cell bodies contain GR IR. Furthermore, neuronal GR IR is found in neuronal populations all over the central nervous system, especially in the cerebral cortex, the thalamus and the hypothalamus, indicating a major role of GR in regulating the metabolic and synaptic functions of the brain. The ER IR is instead limited to certain neuronal populations, mainly those of the preoptic area, the bed nucleus of the striae terminalis and the arcuate nucleus, suggesting a specific role in control of LHRH secretion and reproductive behaviour.

Adrenalectomy↗
PubMed1987

Multipurpose Senior Service Program Deinstitutionalization Screen.

The Multipurpose Senior Services Program Deinstitutionalization Screening Instrument has been designed to identify easily and quickly those patients in nursing homes who are likely to be returned to the community through case-management efforts. The six-item screen and tables allow the interviewer to determine the probability of a patient being successfully discharged from a nursing home.

Activities of Daily Living↗
PubMed1987

Biomechanical analysis of cervical distraction.

A biomechanical analysis of cervical distraction is presented, and a model comparing closed reduction of cervical spine dislocations to spring mechanics is developed. Behavior of a spring may be described as F = k delta x where F = distraction force; delta x = elongation of the spring; and k = spring constant. The records and roentgenograms of 24 cervical spine dislocations were reviewed retrospectively. Evaluation of cervical distraction vs traction weight indicates that Ftraction = kneck delta x; where F = traction weight and x = distraction at the injured level. The constant, kneck, is different for bilateral and unilateral dislocations (P less than .001) and is a function of magnitude of injury and neck morphology. As determined in this study, traction weight needed for reduction of facet dislocations may be estimated using the formulae: Ftx = 107.1 lbs/cm (x) unilateral, and Ftx = 76.4 lbs/cm (x) bilateral.

Adult↗
PubMed1987

Closed reduction of cervical spine dislocations.

Between July 1979 and July 1983, 24 patients with cervical facet dislocations were treated. There were 11 unilateral and 13 bilateral facet dislocations. The treatment consisted of axial skeletal tractions, Stryker frame, Gardner-Wells tongs, and judicious manipulation. Cadaver studies were important for learning the anatomy and principles of cervical manipulation. Seventeen (71%) of the 24 patients were reduced successfully by a closed method without any progression of neurologic deficit or facet fracture. Seven (29%) of the 24 patients could not be reduced closed. Ninety percent (9 of 10) of incomplete spinal cord injuries improved when evaluated by the Frankel classification at least one grade. The program of treatment proved to be safe and effective in achieving closed reduction of either unilateral or bilateral facet dislocations.

Adolescent↗
PubMed1986

Systemic hypertension induces disparate localized left ventricular action potential lengthening and altered sensitivity to verapamil in left ventricular myocardium.

Previously, we demonstrated that acute exposure to superfusate containing verapamil suppresses action potential plateau to a greater degree in cells at the tip of the anterior papillary muscle compared to those at its base in normal cat left ventricle (LV) studied in tissue bath. To determine the effects of chronic pressure overload brought about by renal hypertension on papillary muscle electrophysiology and regional sensitivity to verapamil, LV were isolated from cats subjected to unilateral nephrectomy and contralateral kidney wrapping. After 3 months, systemic hypertension (mean increase = 60.2 +/- 1.4 mmHg) was associated with moderate LV hypertrophy of approximately equal to 18% (LV weight/body weight). Transmembrane action potentials recorded from the endocardial surface (including anterior papillary muscle) in pressure overloaded LV in vitro (800 ms stimulus cycle length) showed increased action potential duration at 25, 75 and 90% of repolarization (APD25, APD75 and APD90, respectively) relative to controls (LV from normal and sham operated cats). With respect to the anterior papillary muscle in pressure overloaded LV, APD25, APD75 and APD90 were increased to a greater extent in cells at the base of the muscle compared to those increases observed at the tip (P less than 0.05). In contrast to its effects in controls, verapamil (2 micrograms/ml) significantly reduced APD25 at both the base and the tip of the papillary muscle in pressure overloaded preparations, but particularly at the base; also, the disparities between the APD75 or APD90 at tip and base were decreased. Thus, regional electrophysiologic disparities were induced in systemic hypertension, and these differences were subsequently reduced by verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1986

Immunocytochemical assay for estrogen receptor in patients with breast cancer: relationship to a biochemical assay and to outcome of therapy.

We developed an immunoperoxidase technique using a monoclonal antibody to the estradiol receptor (ER) to identify immunoreactive ER (iER) in breast carcinomas and compared this with the conventional dextran-coated charcoal (DCC) steroid binding assay. We also examined the relationship between the iER and response to therapy in patients with advanced breast cancer. We found iER-positive cells in 60 of 90 carcinomas (66.7%); this correlated with the DCC assay (r = 0.76; P less than .001). Of these, 56 patients were found to be assessable for response to endocrine therapy. Twenty-two showed an objective response to some form of endocrine manipulation, and all these had positively stained carcinomas. By deriving a staining intensity index (SII) we observed that 21 of 22 responders (95%) had an SII of greater than or equal to 0.5, whereas only 8 of 34 nonresponders (24%) had an SII of greater than or equal to 0.5. This difference is highly significant (P less than .001). None of the 17 patients with negatively stained carcinomas responded to endocrine therapy. We conclude that the monoclonal antibody to ER can help identify breast cancer patients who may respond to endocrine therapy.

Aminoglutethimide↗
PubMed1986

Immunocytochemical assay for estrogen receptor: relationship to outcome of therapy in patients with advanced breast cancer.

We have used an immunoperoxidase technique utilizing a monoclonal antibody to the estradiol receptor to identify immunoreactive estradiol receptor in breast carcinomas and have examined the relationship between the immunoreactive estradiol receptor and response to therapy in patients with advanced breast cancer. Fifty-six patients were found to be assessable for response to endocrine therapy. Twenty-two showed an objective response to some form of endocrine manipulation, and all these had positively stained carcinomas. None of the 17 patients with negatively stained carcinomas responded to endocrine therapy. We conclude that the monoclonal antibody to estradiol receptor can help identify breast cancer patients who may respond to endocrine therapy.

Antibodies, Monoclonal↗
PubMed1986

Detection of estrophilin in frozen sections of breast cancers using an estrogen receptor immunocytochemical assay.

Estrogen receptor (ER) was detected in frozen sections of 36 breast carcinomas using an antiestrophilin monoclonal antibody according to an immunocytochemical technique elaborated and made available by Abbott Laboratories in the form of a kit (ER-immunocytochemical assay monoclonal). Immunostaining was confined to the nuclei of the carcinoma cells. In all positive specimens, nuclei with different staining intensities were present in addition to a variable number of unstained nuclei, presumably because of functional heterogeneity. Of the 36 carcinomas, 27 displayed positive immunostaining, 4 had no staining, and in 5 the staining was borderline. All specimens were assayed for ER content by the dextran-coated charcoal (DCC) technique. When the DCC values were compared with the results of immunostaining it was found that 4 tumors were negative and 27 were positive by both techniques, whereas of 5 cases with borderline staining 3 were negative by DCC and 2 had low DCC values. These correlations proved to be highly significant (P much less than 0.001). The number of stained nuclei (extent of staining) related to the DCC status in a significant manner (P less than 0.01), whereas the intensity of staining did not (P greater than 0.10). These results indicate that immunocytochemical visualization of ER using Abbott's "ER-Immunocytochemical Assay Monoclonal" kit is an easy, reproducible, and reliable technique.

Aged↗
PubMed1986

Cost-effectiveness of the Medicare three-hour regulation.

In September 1982 Medicare instituted a requirement that patients in acute medical rehabilitation hospital units receive a minimum of three hours per day of physical and occupational therapy combined. To investigate the consequences of that policy functional status, charges and other outstanding measures of rehabilitative outcomes were assessed for 934 patients before and after implementation of the regulation. After the regulation, average daily intensity of physical plus occupational therapy increased 0.55 hours per patient day, adding charges of $408,000 over the sample. The increased intensity of therapy provided no detectable benefit to patients in terms of improved functional status, living arrangement, or other outcomes. Results underscored the importance of grading the intensity of rehabilitation to the varying needs of patients.

Aged↗
PubMed1986

The use of plasma melatonin levels and light in the assessment and treatment of chronobiologic sleep and mood disorders.

Using the highly accurate and sensitive gas chromatographic-negative chemical ionization mass spectrometric assay for plasma melatonin we have measured plasma melatonin in humans as a biological marker for 24-hour (circadian) and seasonal rhythms and the effects of light on these rhythms. We propose that there are at least three critical parameters for light to be chronobiologically active in humans: intensity, wavelength and timing. With regard to timing, we have found that bright light exposure in the morning advances circadian rhythms (shifts them to an earlier time) and bright light in the evening delays them (shifts them to a later time). We have suggested that chronobiologic sleep and mood disorders be "phase typed" into either the phase advance subtype or the phase delayed subtype and that these disorders can then be treated with either evening light (for phase advanced disorders) or morning light (for phase delayed disorders). Regarding the function of melatonin in humans, we have preliminary evidence that it may participate in the regulation of the circadian rhythm of intraocular pressure.

Biological Clocks↗
PubMed1985

Reduction in RNA synthesis following red cell-mediated microinjection of antibodies to RNA polymerase I.

Antibody molecules directed against RNA polymerase I, the enzyme responsible for rRNA synthesis, were introduced into rat hepatoma cells by red cell-mediated microinjection. Access of the antibodies to the nucleolus, the site of rRNA synthesis, was facilitated by microinjecting mitotic cells. Using indirect immunofluorescence, anti-RNA polymerase I immunoglobulins, but not control immunoglobulins, were found localized in the nucleoli of microinjected cells. To assess whether intracellular antibodies could alter RNA synthesis, cultures were labeled with [3H] uridine at various times after microinjection. Reduction in RNA synthesis, relative to cells microinjected with non-immune immunoglobulins, was observed within three hours. These results demonstrate that antibodies introduced into the cytoplasm of mitotic cells via red cell-mediated microinjection have free access to nuclear components and that they remain functional within the nuclei of living cells.

Animals↗
PubMed1985

Differential effects of calcium antagonists on viability of adult rat ventricular myocytes.

This study was designed to determine whether the various classes of Ca2+ channel blockers have differential protective effects on isolated adult rat ventricular myocytes exposed to high K+ under anoxic (100% N2) conditions. Calcium-tolerant myocytes were incubated under control (4mM K+) aerobic conditions and then subjected to high K+ (75 mM) and N2. The cells were assessed by morphological criteria (i.e. absence of blebbing, granulation etc.), maintenance of ATP levels, exclusion of trypan blue, and the presence or absence of spontaneous contractile activity. Under control conditions, the cells were quiescent and declined at a rate of approximately 10%/h. In the absence of O2, the rate of cell decline was significantly faster. Verapamil, diltiazem and the dihydropyridines had no significant effects on cell decline under these conditions. Cells exposed to 75 mM K0+ exhibited contractile activity and accelerated rate of decline under anoxic conditions; these effects were independent of lowering Na0+ to 75mM. Cells in high K0+ and N2 were significantly protected (i.e. contractile activity and rate of decline were decreased) by verapamil, less so by diltiazem, and not at all by the dihydropyridines. The uptake of 45Ca2+ into cells in high K0+ was not significantly altered by verapamil or diltiazem. Caffeine induced the immediate cessation of contractile activity of cells incubated in high K0+, but did not affect the accelerated rate of cell declined under anoxic conditions. Verapamil and diltiazem still conferred significant protection in this non-beating cell preparation. Neither verapamil nor diltiazem had any effect on the oscillation frequency of skinned heart cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1985

Immunocytochemical staining of estrogen receptor in paraffin sections of human breast cancer by use of monoclonal antibody: comparison with that in frozen sections.

Estrogen receptor (ER) in human breast cancer tissues was demonstrated in paraffin sections as well as in frozen sections by immunoperoxidase methods using monoclonal antibody (H222) against ER. The avidin-biotin-peroxidase complex method was used for the paraffin sections fixed in cold buffered formalin, and the peroxidase-antiperoxidase method was used for the fixed frozen sections. The results were compared with the ER content in the respective tumor tissue determined by dextran-coated charcoal assay. The specific staining for ER was located exclusively in the nuclei of cancer cells in both paraffin and frozen sections. Differences in the intensity and distribution of nuclear staining within a section were often observed, suggesting heterogeneity of the ER content of individual breast cancer cells. In 24 breast cancer tissues studied simultaneously by both paraffin and frozen section methods, 21 (88%) showed similar evaluation of the presence of ER. The results of immunocytochemical staining agreed with those of the dextran-coated charcoal assay in 89 (82%) of the 109 paraffin-sectioned tumor tissues and in 24 (86%) of the 28 frozen-sectioned tissues, indicating that ER can be demonstrated immunocytochemically by use of paraffin as well as frozen sections.

Antibodies, Monoclonal↗