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Biomedical subjects

B Miller

Publications and source records attributed to B Miller.

At least 199 records · Page 11Linked to original sources

Concentration of serum amyloid P component in the CSF as a possible marker of cerebral amyloid deposits in Alzheimer's disease.

Serum amyloid P component (SAP) is a normal plasma protein produced in the liver and co-deposited with amyloid fibrils in all types of amyloidosis, including cerebral beta-protein amyloid deposits associated with Alzheimer's disease (AD). We have measured its concentration and those of alpha 2-macroglobulin, IgG and albumin in the CSF of 51 patients with AD and 50 healthy and disease control subjects. The mean levels of SAP were 12.8 ng/ml in AD and 8.5 ng/ml in controls (P < 0.0125); there was no difference in the levels of the other proteins studied. The observed concentrations of SAP were much lower than expected for a protein of molecular weight 254620. The difference between AD and controls suggests that the concentration of SAP in the CSF may be affected by the presence of cerebral amyloidosis.

Aged↗

Orientation-conserved transfer of symmetric Krebs cycle intermediates in mammalian tissue.

Metabolism of [2-13C]-, [3-13C]-, and [1,2,3-13C]propionate in perfused rat livers and [2-13C]-acetate in perfused rat hearts has been examined in tissue extracts by 13C NMR. Label from [2-13C]-propionate was preferentially incorporated into the C2 carbon of lactate, alanine, and aspartate in liver tissue while label from [3-13C]propionate appeared preferentially in the C3 carbon of those same molecules. These data suggest that 13C may not be completely randomized in the symmetric citric acid cycle intermediates succinate and fumarate as is normally assumed but that some fraction of those intermediates may be transferred between enzymes in this span of the cycle with conservation of spatial orientation, consistent with recent results obtained in yeast [Sumegi et al. (1990) Biochemistry 29, 9106-9110]. This was confirmed by performing similar experiments with [1,2,3-13C]propionate. Time-dependent asymmetry was also observed between the intensities of the glutamate C2 and C3 resonances and between the aspartate C2 and C3 resonances in 13C NMR spectra of intact hearts and heart extracts during early perfusion with [2-13C]-acetate. A model is presented which predicts that isotopic asymmetry is observed only during the first 2-3 turns of the cycle pools when isotope enters the cycle via acetyl-CoA even if all symmetric cycle intermediates retain a unique molecular orientation on each pass through the citric acid cycle.

Acetates↗

Arachidonic acid depresses non-NMDA receptor currents.

Arachidonic acid has been proposed as an intercellular messenger in the nervous system. It is released when glutamate acts on postsynaptic receptors, potentiates NMDA receptor currents and depresses glutamate uptake. Here we report the effects of arachidonic acid on non-NMDA receptor currents, studied by whole-cell clamping isolated neurons and neurons in tissue slices. In cultured cerebellar granule cells and in freshly isolated hippocampal pyramidal cells arachidonic acid decreased the current produced by iontophoresed AMPA. This depression was not due to increased desensitization of the AMPA receptor. In cerebellar slices, arachidonic acid depressed the non-NMDA component of the synaptic current at the mossy fibre to granule cell and the parallel fibre to Purkinje cell synapses. However, this depression was not always seen, possibly because the lipophilic arachidonic acid is absorbed by superficial cells in the slice and does not reach the synapse being studied. Depression of non-NMDA receptor currents by arachidonic acid may reflect the presence of an arachidonic acid binding site on the non-NMDA receptor, but non-NMDA receptor subunits show much less sequence homology with fatty acid binding proteins than does the NMDA receptor.

Amino Acid Sequence↗

Oscillatory behavior of control-systems of calcium homeostasis in chickens.

Computer simulation of calcium homeostasis in chicks predicted an oscillatory behavior of bone calcium flow and kidney 25-hydroxyvitamin D3-1-hydroxylase with a periodicity of 56 h and a 9 h phase difference between the two signals. In growing chickens subjected to a light: dark cycle of 22:2 h, and intravenously dosed with 45Ca, the temporal changes in plasma 45Ca could be described by an exponential decline with superimposed diurnal oscillations. The activity of the renal 25-hydroxyvitamin D3-1-hydroxylase in chicks subjected to a 12:12 h light: dark cycle ALSO followed diurnal oscillations, with a nadir at the beginning of the light period and a peak 12 h later. The production of 1,25-dihydroxyvitamin D3 by primary cultures of chicken kidney cells oscillated with a periodicity of 5.6 h or shorter. It is suggested that despite the differences in phase and periodicity between the simulation predictions and actual results, the oscillations in both 1-hydroxylase and bone calcium flow could be coupled through the hormonal systems involved in regulation of plasma calcium.

Aging↗

Nucleolar organizer regions: a potential prognostic factor in adenocarcinoma of the endometrium.

Nucleolar organizer regions, which are evaluated using a silver stain for paraffin-embedded sections (AgNOR), can be used as a measurement of cellular proliferative activity. In the endometrium significant differences have been seen between benign and malignant lesions. To determine if AgNOR counts are of prognostic value in endometrial cancer, we examined 28 patients who developed recurrent disease after surgical stage Ib and Ic endometrial cancer and compared this group with a matched control group of patients who did not develop recurrence. The mean AgNOR number per cell was significantly higher in patients with recurrent disease (P = 0.001). Only five of these patients had values less than 4, whereas only three of the control group had values higher than 4. There was also a significant difference in the percentage of cells with more than 5 and more than 8 AgNORs (P = 0.001). After radiation therapy, the number of AgNORs per cell decreased. Recurrent tumors had higher AgNOR counts than the respective primary tumors. In conclusion, patients at increased risk for recurrent endometrial cancer can be identified by high AgNOR counts. Further evaluation of this parameter and comparison to other prognostic factors seems warranted.

Adenocarcinoma↗

The role of lipids in nephrosclerosis and glomerulosclerosis.

Hyperlipidemia and lipoprotein abnormalities are often encountered in patients with nephrotic syndrome or chronic renal disease and also in those undergoing haemodialysis and with renal transplant. Even though the significance of lipid deposition in renal tissue and the role of lipoproteins in the pathogenesis of renal disease in man is unclear, experimental and clinical data indicate a possible damaging effect of a disturbed lipid metabolism on the kidney. In humans, glomerular lipid deposition is observed in genetic diseases such as Fabry's disease, lecithin:cholesterol acyltransferase activity (LCAT) deficiency and arteriohepatic dysplasia, and in diseases with acquired disturbance of lipid metabolism such as nephrotic syndrome and cholestatic liver disease. Studies on animals with lupus nephritis, aminonucleoside nephrosis, reduced renal mass, diabetes mellitus or systemic hypertension have shown that cholesterol can increase the incidence of glomerulosclerosis. As most of these studies have been performed in the rat, which has a different lipoprotein profile to that of man, these results should be carefully interpreted with regard to their relevance for humans. In vitro cell culture studies on human glomerular cells have given some preliminary insights into the cellular mechanisms of lipid induced glomerular damage. Apo E-containing lipoproteins, which are pathologically elevated in many renal diseases, are avidly taken up by human mesangial cells. These cells seem to play a central role in the initiation of glomerulosclerosis by inducing proliferation and production of excess extracellular matrix. Lipoproteins are able to stimulate DNA synthesis in these cells, and increase the synthesis of mitogens and extracellular matrix protein. The pathogenic role of oxidized lipoproteins has not yet been defined. Human mesangial cells do not seem to take up these modified lipoproteins. However, macrophages infiltrate glomeruli and may constitute the stimulus for the generation of minimally modified lipoproteins and their cellular uptake. The data from animal experiments suggest that treatment that corrects hyperlipidemia may have an ameliorative effect on renal function. Thus, there are strong indications that lipoproteins may play a critical role in mediating the development of glomerulosclerosis.

Animals↗

Association of Chlamydia IgG Titers with Laproscopic Findings of Dystrophic Calcification and Hydrosalpinges but not with Endosalpingiosis

Psammoma bodies are discrete forms of dystrophic calcification which represent cross-sections of calcified papillary formations. At laparoscopy, these have been confused with both endometriosis and cancer. A recent abstract (Khare et al: AAGL, 1993) reported the association of peritoneal psammoma bodies (grain-like inclusions) with positive IgG chlamydia titers (p=0.012). The purpose of this study is to investigate a possible correlation of chlamydia IgG titers with endosalpinges. Histologic slides and charts of 60 consecutive women were reviewed in a blinded fashion for calcification, hydrosalpinx, endosalpingiosis, and other significant changes. Although dystrophic calcification and hydrosalpinges were associated with positive chlamydia IgG titers (p<0.05), endosalpingiosis was found in only one patient. This study confirms previous studies in showing a relationship of chlamydia IgG titers with dystrophic calcification and hydrosalpinges but did not demonstrate a relationship with endosalpingiosis.

Journal Article↗

Changes in sources of community long-term care among African American and white frail older persons.

This study examined race differences in changes in source of long-term care. We addressed the following questions: (1) Are there differences between African Americans and Whites in the patterns of transitions among community longterm care, institutionalization, and death? (2) Are there differences between African American and White populations in sociodemographic characteristics and functional limitations influencing source of long-term care in a two-year follow-up sample? (3) Controlling for socioeconomic status, health status, level of informal care, and demographic variables, are there differences between African Americans and Whites in patterns of change to informal and mixed (informal and formal) care among community-dwelling frail older persons? and, (4) What are the predictors of change patterns within African American and White populations of older frail persons? The source of data is the longitudinal component of the 1982-1984 National Long Term Care Survey (NLTCS). Results of multinomial logistic analysis indicate few differences in change patterns, despite differences in the context of care among African American and White frail older persons.

Black or African American↗

An acute care physical therapy clinical practice database for outcomes research.

Clinical practice databases are frequently used to assess outcomes in various medical specialties. Formulating a computerized physical therapy medical record requires standardization of clinical assessments among the users. The purpose of this article is to describe an acute care physical therapy database system that emphasizes high-quality measures of function. The logic underlying the development of a physical therapy computerized medical record is described. Selected uses of the database are demonstrated by projects that assess data quality, generate clinical hypotheses, manage clinical data, develop clinical measures, and generate pilot data on patient variability. Patients seen in physical therapy for total joint replacement, pain, and decreased ambulation were studied to demonstrate some of the present capabilities of the database. Clinical practice databases contribute to the overall research mission, provided the data are of high quality. The use of databases in conjunction with randomized clinical trials may serve an important role in determining effective physical therapy interventions to reduce disability.

Database Management Systems↗

Erythrocytes from young but not elderly donors can bind and degrade immune complex- and antibody-bound C3 in vitro.

In situ aged erythrocytes (senescent erythrocytes from young donors and both young and old erythrocytes from elderly donors) demonstrate high levels of membrane-bound C3c and C3d and elevated susceptibility to in vitro phagocytosis. In this study we demonstrate that in situ aged erythrocytes are defective in their ability to degrade C3 fragments and clear them from the erythrocyte membrane. Erythrocytes from young donors bind complement-bearing immune complexes via CR1 and become susceptible to complement-mediated erythrophagocytosis ('innocent bystander' sequestration). Erythrocytes from elderly donors are defective in their ability to bind such immune complexes, as attested by the lack of an increment in membrane-associated C3 fragments as detected by flow cytometry and lack of an increment in in vitro sequestration. Factor I (serum)-dependent cleavage of C3 fragments and release of immune complexes from the erythrocytes of young donors lead to a drop in erythrocyte-associated C3 fragments and the disappearance of the 'innocent bystander' phenomenon. Inhibition of Factor I, and thus inhibition of C3b degradation and immune complex release for the erythrocyte membrane, enhances the levels of 'innocent bystander' sequestration of erythrocytes from young donors. Erythrocytes from elderly donors are defective in the dynamic process of CR1 binding of complement-bearing immune complexes and Factor I-associated release of membrane-associated C3 fragments. A defect in the ability of all in situ aged erythrocytes to clear their membranes of C3 fragments is also demonstrated for complement bound to the erythrocyte via IgM isoagglutinins. While erythrocytes from both young and elderly donors allow for the IgM-mediated binding of complement to the erythrocyte, only young erythrocytes from young donors demonstrate degradative activity with the release of membrane-associated C3c. Erythrocytes from elderly donors demonstrate lower levels of detectable CR1 (CD35), decay accelerating factor (DAF) (CD55) and Protectin (CD59) than do erythrocytes from young donors. Time course studies determine that the defect in handling of immune complexes observed for in situ aged erythrocytes is not due to differences in the kinetics of loading or releasing of immune complexes. These findings on the refractiveness of erythrocytes of elderly donors to uptake of immune complexes and the degradation of C3 fragments may be of importance not only in the understanding of erythrocyte sequestration, but also in the physiology of immune clearance in the elderly.

Adolescent↗

Disease-induced changes in alpha-adrenoceptor-mediated cardiac and vascular responses in rats.

1. The physiological relevance of cardiac and vascular alpha-adrenoceptors may increase in disease states in which beta-adrenoceptors are altered. To test this, positive inotropic and vasoconstrictor responses to phenylephrine were measured in isolated tissues from rats with experimentally-induced hyperthyroidism, hypothyroidism and diabetes as well as in genetically spontaneous hypertensive rats (SHR). 2. In left atria, positive inotropic responses to phenylephrine were increased in hypothyroid and diabetic rats and abolished in hyperthyroid and SHR. 3. In contrast, phenylephrine produced increased positive inotropy in left ventricular papillary muscles from hyperthyroid rats, increased potency in diabetic rats and negative inotropic responses in hypothyroid rats. 4. The potency of phenylephrine as a vasoconstrictor in thoracic aortic rings was increased in hyperthyroid and SHR and decreased in hypothyroid rats. 5. Thus, disease states which alter beta-adrenoceptor responsiveness can independently regulate atrial, ventricular and vascular responses to the alpha 1-adrenoceptor agonist, phenylephrine. Therefore, these disease states may alter the physiological control of the cardiovascular system by noradrenaline and adrenaline as well as the responsiveness in disease states to therapeutic agents acting via alpha-adrenoceptors.

Animals↗

Cognitive functioning in a mildly to moderately depressed geriatric sample: relationship to chronological age.

The neuropsychological performance of three age cohorts of depressed patients (46-59, 60-69, and 70-85) was compared with the performance of age-matched control subjects to determine whether advancing age potentiates the effect of depression on cognition. Depression and increasing age did not interact to produce more pronounced cognitive deterioration in our unmedicated, medically healthy, well-educated outpatients diagnosed with mild to moderate major depression. Test findings suggest that presence of mild to moderate depression may result in premature "aging" of specific cognitive abilities (such as nonverbal memory, word generation, and categorization), but once the seventh decade is reached, cognition in depressed and nondepressed individuals appears to be comparable.

Age Factors↗

Trends in breast cancer in younger women in contrast to older women.

Using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics, trends in female breast cancer rates were examined for the time period 1973-1989 for the age group 20-39 and contrasted with those for older ages. Only about 7% of breast cancers occur by the age of 40; the risk of developing breast cancer prior to the age of 40 is less than 1%. The incidence trends for women in the 20-39 age group have been essentially stable, whereas for women 40 and older the rates increased steeply during the 1980s (at a faster rate than anticipated based on historical trends) and then leveled off beginning in 1987. Breast cancer mortality has been much more stable over time than incidence. Up to age 40, blacks have a higher incidence than whites. Over age 40, white rates exceed those for blacks, and the absolute and relative differences in incidence increase with advancing age. For whites, 5-year relative survival rates improved with advancing age up to age 50. Blacks under the age of 30 had survival rates similar to whites, whereas, in the older age groups, whites had somewhat better survival rates overall and by stage. The occurrence of second cancers was also analyzed in women with a first invasive breast cancer. Cancers found to occur at higher than expected rates included leukemia and cancers of the breast, ovary, and lung.

Adult↗

The effect of a surgical lubricant on in vivo sperm penetration of cervical mucus.

The implications of these data is that coital lubricants may impair fertility of some couples. Unfortunately, conception was not an end point on this study, and our conclusions must be considered inferential. Nevertheless, the results from this study lead us to recommend avoidance of surgical lubricants by couples attempting pregnancy.

Adult↗