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Biomedical subjects

B Miller

Publications and source records attributed to B Miller.

At least 217 records · Page 12Linked to original sources

Low-density lipoprotein subclass patterns and lipoprotein response to a reduced-fat diet in men.

Low-density lipoprotein (LDL) subclass pattern B is a common genetically influenced lipoprotein profile characterized by a predominance of small, dense LDL particles, and associated with increased levels of triglyceride-rich lipoproteins, reductions in high-density lipoprotein cholesterol (HDL-C), and increased risk of coronary artery disease compared to individuals with a predominance of larger LDL (pattern A). We sought to determine whether LDL subclass patterns are associated with response of plasma lipoprotein levels to changes in dietary fat and carbohydrate content. In a randomized cross-over study, 105 men consumed, for six weeks each, high-fat (46%) and low-fat (24%) solid food diets, with replacement of fat by carbohydrate. Diet-induced changes in subjects who exhibited pattern B (n = 18) following the high-fat diet differed significantly from those in subjects with pattern A (n = 87): in pattern B subjects LDL cholesterol (LDL-C) reductions were two-fold greater and plasma apolipoprotein (apo) B levels decreased significantly. These differences remained significant after adjustment for levels of plasma LDL-C, apo B, HDL-C, and body mass index. Thus, LDL subclass pattern is a factor that contributes significantly to interindividual variation of plasma lipoprotein response to a low-fat, high-carbohydrate diet.

Adult↗

Influence of systemic diseases and environmental factors on age at appearance, location and type of acquired cataract.

We studied 257 patients scheduled for cataract surgery for possible correlation with systemic diseases, blood chemistry, and environmental exposure. We found that posterior subcapsular cataract appeared in patients 10 years younger on average than those with other types of cataract. Nuclear cataract patients had higher blood levels of uric acid and creatinine and lower blood levels of calcium. We suggest capsular insult as a possible pathophysiological explanation for cataract formation in young age groups (as well as diabetes) and a toxic effect of blood metabolites in patients with renal failure, resulting in earlier and more prevalent sclerosis of lens fibers. No effect of smoking or of exposure to sunlight on the distribution of various types of cataracts was noted.

Age Factors↗

The early development of thalamocortical and corticothalamic projections.

The early development of thalamocortical and corticothalamic projections in hamsters was studied to compare the specificity and maturation of these pathways, and to identify potential sources of information for specification of cortical areas. The cells that constitute these projections are both generated prenatally in hamsters and they make reciprocal connections. Fluorescent dyes (DiI and DiA) were injected into the visual cortex or lateral geniculate nucleus in fixed brains of fetal and postnatal pups. Several issues in axonal development were examined, including timing of axon outgrowth and target invasion, projection specificity, the spatial relationship between the two pathways, and the connections of subplate cells. Thalamic projections arrive in the visual cortex 2 days before birth and begin to invade the developing cortical plate by the next day. Few processes invade inappropriate cortical regions. By postnatal day 7 their laminar position is similar to mature animals. By contrast, visual cortical axons from subplate and layer 6 cells reach posterior thalamus at 1 day after birth in small numbers. By 3 days after birth many layer 5 cell projections reach the posterior thalamus. On postnatal day 7, there is a sudden increase in the number of layer 6 projections to the thalamus. Surprisingly, these layer 6 cells are precisely topographically mapped with colabeled thalamic afferents on their first appearance. Subplate cells constitute a very small component of the corticothalamic projection at all ages. Double injections of DiI and DiA show that the corticofugal and thalamocortical pathways are physically separate during development. Corticofugal axons travel deep in the intermediate zone to the thalamic axons and are separate through much of the internal capsule. Their tangential distribution is also distinct. The early appearance of the thalamocortical pathway is consistent with an organizational role in the specification of some features of cortical cytoarchitecture. The specific initial projection of thalamocortical axons strongly suggests the recognition of particular cortical regions. The physical separation of these two pathways limits the possibility for exchange of information between these systems except at their respective targets.

Afferent Pathways↗

Breast cancer among black and white women in the 1980s. Changing patterns in the United States by race, age, and extent of disease.

BACKGROUND: This national study of breast cancer incidence and mortality was conducted to determine whether patterns of change differ for black and white women, to evaluate patterns by extent of disease, and to determine whether recent patterns of breast cancer are consistent with results that one would expect due to increases in use of screening examinations by women. METHODS: The study included 104,351 cases of in situ or invasive breast cancer diagnosed between 1983 and 1989 among women from the nine geographic areas participating in the National Cancer Institute Surveillance, Epidemiology, and End Results program. Breast cancer incidence patterns were examined by extent of disease for black and white women and by age at diagnosis. RESULTS: Significant increases occurred in the incidence of all early-stage breast cancers. Concomitantly, significant decreases occurred in the incidence of the most advanced-stage breast cancers. Although both white and black women experienced significant increases in early-stage breast cancer, black women have substantially lower rates of the least extensive breast cancers. CONCLUSIONS: These results strongly suggest that a major explanation for the increase in breast cancer incidence in the 1980s may well be the increased prevalence of breast cancer screening among women in the United States. They also suggest a consistent benefit of screening across all age groups from 40 to 49 years through 70 years and older.

Adult↗

Reliability and usefulness of a new immunochemical assay for Alzheimer's disease.

OBJECTIVE: To assess the reliability and usefulness of a new sandwich enzyme-linked immunoassay (ALZ-EIA) that detects Alzheimer's disease-associated proteins in the diagnosis of Alzheimer's disease. DESIGN: The reliability of the assay was assessed between two laboratories. Sensitivity and specificity of a diagnostic algorithm based on the results of the ALZ-EIA were determined using the Consortium to Establish a Registry for Alzheimer's Disease neuropathological diagnoses as the "gold standard." SETTING: Autopsy cases were obtained from a teaching hospital with a specialized Alzheimer Disease Diagnostic and Treatment Center. CASES: Brain tissue was selected from 24 cases with dementia and 10 normal controls. MAIN OUTCOME MEASURES: Optical density measurements from the ALZ-EIA in the hippocampus and three neocortical regions. RESULTS: A 95% concordance in ALZ-EIA activity was found between the two laboratories, and an 85% concordance was found between ALZ-EIA and the Consortium to Establish a Registry for Alzheimer's Disease diagnoses. Perfect agreement was obtained for "typical" Alzheimer's disease cases (those with plaques and tangles), while discrepancies occurred for "atypical" cases (those with predominantly plaques or tangles). CONCLUSIONS: The ALZ-EIA provides a highly reliable method of assessing neurofibrillary degeneration. Its clinical usefulness as a diagnostic test would be enhanced by the availability of a complementary assay for beta-amyloid.

Aged↗

Photodynamic therapy of subretinal neovascularization in the monkey eye.

Experimental subretinal neovascularization in the monkey eye was treated by photodynamic therapy with rose bengal. Following intravenous injection of rose bengal, the subretinal vessels were irradiated with filtered light. Successful treatment was achieved, provided the subretinal vessels were irradiated during the period in which the dye was present in and around the subretinal vessels but had already cleared from the retinal vasculature. The successfully treated lesions demonstrated replacement of the leaking and pooling subretinal vessels with a non-leaky scar. Morphologic evaluation revealed immediate destruction of the subretinal plexus, with minimal damage to the overlying retina. The destroyed subretinal tuft was replaced by a scar containing mainly fibroblasts embedded in collagen fibers. Our results suggest that photodynamic therapy is potentially useful for destruction of subretinal vessels without damaging the overlying retina.

Animals↗

Consequences of reduced cerebral blood flow in brain development. I. Gross morphology, histology, and callosal connectivity.

Reduced blood flow produced by bilateral carotid artery occlusion (BCAO) caused multiple histopathological alterations in the cerebral cortex of developing cats. BCAO was performed in the second postnatal week. At 1 and 2 months, global structural observations were made using magnetic resonance imaging (MRI). At 3 months, neuron and glial density, extent of myelination, blood vessel distribution, and the distribution of visual callosal projecting neurons (as visualized with the retrogradely transported tracer horseradish peroxidase) were assessed by light microscopy. MRI showed lateral ventricular dilatation at 1 month in five of eight subjects, with wide-ranging severity, although at 2 months only two animals still had enlarged ventricles. Histological observations at 3 months showed that neuron density in the motor cortex, but not the occipital cortex, of BACO animals was significantly lower than that in controls. BCAO animals had more dilated small vessels, again more evident in the motor cortex than in the occipital cortex. From frontal to occipital cortex, the corpus callosum was thinned and the subcortical white matter was reduced. Even with the reduction of white matter, the number of neurons in visual areas 17 and 18 contributing a callosal projection was much higher than normal. BCAO thus altered cerebral vascularization, caused neuronal death, and reduced myelinization over an area much greater than the direct area of carotid perfusion. The excess callosal projection in these animals suggests that neonatal ischemia interferes with the normal process of axon retraction during development.

Aging↗

Consequences of reduced cerebral blood flow in brain development. II. Retardation of neurological outcome and phosphorus metabolism.

We investigated the temporal relationship of the emergence of biochemical abnormalities to the development of behavioral dysfunction to identify the central factors of ischemic neurological disorders in developing brains. To induce early ischemia, bilateral carotid artery occlusion (BCAO) was surgically performed on 21 cats at the second week of age. BCAO produces histopathological damage, including neuronal loss and thinning of white matter. 31P magnetic resonance spectroscopy was used to monitor brain oxidative metabolism, neuronal membrane growth, and myelination of the prefrontal cortex in the first 3 months. Neurological development was monitored by conducting 25 tests of reflex, motor, sensory, and integrated behavioral function. At 1 month, phosphodiester (PDE) levels, a component of membranes and myelin, were low in animals showing complete ligation. At 2 months, the growth of PDE was low (1/4 to 1/2 of normal) in BCAO animals, whereas normal animals demonstrated a 23% increase. Phosphocreatine (PCr) levels, indicated by PCr/ATP and PCr/inorganic phosphate ratios, were retarded at 2 months in completely ligated animals (1/4 of normal). Neurologically, the completely ligated animals showed retardation of general development. The retardation was most pronounced for integrative functions, including visual function, and became more pronounced later in development. The time course of emergence of the retardation generally coincided with emergence of abnormalities in phosphorous compounds. The simultaneous occurrence of several biochemical and functional abnormalities in development following early ischemic insult suggests a causal relationship between membrane and mitochondrial development and neurological function.

Adenosine Triphosphate↗

Aborted exenterative procedures in recurrent cervical cancer.

Preparation for pelvic exenteration is a traumatic experience for every patient, especially so when the procedure has to be aborted because of advanced disease. This occurred in 111 of 394 patients who underwent exploration for possible pelvic exenteration for recurrent cervical cancer at the University of Texas M. D. Anderson Cancer Center between 1970 and 1990. We reviewed these cases to better delineate preoperative factors predictive of unresectability. Distributions of initial stages and pathological diagnoses were similar to those for all cases of primary cervical cancer. The median time from primary therapy to recurrence was 12 months. The reasons for aborting the procedure included the presence of peritoneal disease in 49 patients (44%), for which the only preoperative finding with significant correlation was the presence of a pelvic mass (P = 0.03). Other reasons for aborting the procedure included nodal disease in 45 patients (40%), related to a short interval from primary therapy (P = 0.008) and the notation of fibrosis on preoperative exam (P = 0.01), parametrial fixation in 15 patients (13%), and hepatic lesions or bowel involvement in 5 patients (4.5%). Peritoneal cytology was negative in 61 of 79 patients (77.2%) and was of predictive value only in patients with adenocarcinoma. In conclusion, disseminated disease can seldom be detected during preoperative work-up. Evaluation of nodal status with computed tomography, lymphangiogram and directed fine-needle aspiration, and examination of peritoneal cytology in cases with adenocarcinoma, are the best available means of reducing the number of aborted procedures.

Adult↗

The effect of intravenous magnesium administration on aortic, right atrial and coronary perfusion pressures during CPR in swine.

OBJECTIVE: To determine the effect of magnesium administration on aortic, right atrial and coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR). DESIGN: Twelve swine weighing 23.2 +/- 3.1 kg were instrumented for CPP, aortic systolic (AOSP) and aortic diastolic (AODP) pressures. INTERVENTION: Ventricular fibrillation was induced and after 20 min of CPR the animals were allocated to receive epinephrine 0.2 mg/kg, or epinephrine 0.2 mg/kg plus magnesium 0.14 g/kg. Epinephrine was repeated every 5 min. Arterial blood gases were determined during normal sinus rhythm and prior to drug administration. RESULTS: Pressures were recorded and averaged over four consecutive 5-min intervals following initial drug administration. AOSP, AODP and CPP were compared using an analysis of covariance. AOSP was statistically lower in the group receiving magnesium. There was a trend toward lower AODP and CPP in the group receiving magnesium as well. These statistical differences and trends were absent after adjusting for pressures during normal sinus rhythm and serum bicarbonate prior to drug administration. CONCLUSIONS: In this model of prolonged cardiac arrest, the administration of magnesium with epinephrine appeared to have a negative effect on aortic pressures during CPR. Further study is needed to determine the confounding effect of serum bicarbonate on the response to epinephrine and magnesium during CPR.

Animals↗

Glutamate uptake from the synaptic cleft does not shape the decay of the non-NMDA component of the synaptic current.

To study the role of glutamate uptake at central glutamatergic synapses, we used the uptake blocker L-transpyrrolidine-2,4-dicarboxylate (PDC). The effects of PDC on the glutamate uptake current in salamander retinal glia indicated that PDC competes with glutamate for transport on the uptake carrier and that 300 microM PDC should significantly reduce the uptake of glutamate during the synaptic current. In isolated rat hippocampal neurons, 300 microM PDC did not affect non-N-methyl-D-aspartate (NMDA) receptor currents, but reduced NMDA receptor currents by 30%. In hippocampal and cerebellar slices, whereas 300 microM PDC reduced the NMDA component of excitatory synaptic currents by 50%, it reduced the non-NMDA component only slightly with no change in its decay time constant. Thus, the decay rate of the non-NMDA component is not set by the rate of glutamate uptake from the synaptic cleft into the presynaptic terminal.

Animals↗

Failure to detect gonadotrophin-releasing hormone receptors in human benign and malignant breast tissue and in MCF-7 and MDA-MB-231 cancer cells.

We have measured the binding of radiolabelled analogues of gonadotrophin-releasing hormone (GnRH) to homogenates of human breast cancer and benign breast tissue, and to MCF-7 and MDA-MB-231 cell lines. Although incubation of breast cancer homogenates with the 125I-labelled GnRH agonist analogues, buserelin [(D-Ser tBU6)GnRH 1-9 ethylamide] and tryptorelin [(D-Trp6) GnRH 1-9 ethylamide] appeared to show significant though low, specific GnRH agonist binding in a high proportion of breast cancers (32/42 for buserelin; 15/32 for tryptorelin) and benign breast tissues (13/16 for buserelin; 10/12 for tryptorelin), after correction for displaceable binding in control assay tubes, GnRH agonist binding to breast tissue was no longer apparent. The lack of specific binding was not due to inactivation of GnRH agonist tracers, as > 86% of the unbound tracer was still capable of rebinding to fresh placental membranes after incubation with breast cancer homogenates. GnRH agonist did not bind to MCF-7 and MDA-MB-231 cells, however GnRH agonist tracer inactivation following exposure to these cells was very high. We have shown recently that human placental receptors bound salmon GnRH and chicken GnRH II as well as GnRH agonists, but not other isoforms of GnRH. However, no isoform of GnRH bound significantly to human breast tumour tissue. In summary, we could not confirm the presence of specific GnRH binding sites in homogenates and membranes from human breast tissues in this study. Low levels of apparently specific binding of GnRH agonist tracers could be accounted for entirely by displacement of tracer from assay tubes. Inability to demonstrate specific binding was not due to extensive inactivation of GnRH tracers (although this may be a factor in the failure to demonstrate GnRH binding to MCF-7 and MDA-MB-231 cell lines).

Animals↗

Role of lipoproteins in progressive renal disease.

Renal diseases are often associated with hyperlipoproteinemia and dyslipoproteinemia. Total serum cholesterol and triglycerides are increased in nephrotic syndrome regardless of etiology. Approximately 40 to 50% of patients with renal insufficiency requiring hemodialysis show hypertriglyceridemia and dyslipoproteinemia. During chronic hemodialysis, high doses of unfractionated heparin deplete post-heparin lipolytic activity and aggravate dyslipoproteinemia. Hypercholestrolemia and hyperlipoproteinemia are often encountered in patients taking glucocorticoids and cyclosporin A after renal transplantation. Observations in experimental animals and in patients with genetically determined and acquired hyperlipidemias suggest that lipids can damage the kidney and lead to glomerulosclerosis. In vitro cell-culture studies of human glomerular cells have been useful in providing information on lipid-induced glomerular damage. Thus, there are strong indications that lipoproteins may play a critical role in the development of mesangial cell damage and progressive renal disease. Therapeutic measures that reduce and correct dyslipoproteinemia in renal disease may have long-term beneficial effects on the amelioration of renal disease.

Humans↗

Radiofrequency catheter ablation for AV nodal reentry: a technique for rapid transection of the slow AV nodal pathway.

Selective radiofrequency (RF) catheter ablation of the slow AV nodal pathway has shed new light on the anatomy and physiology of the atrioventricular junction. The recording of "slow pathway potentials" facilitates localization of the slow pathway and has led to a concept of multiple pathway components with atrial insertion sites covering a potentially broad region surrounding the coronary sinus os. The critical area for complete interruption of the slow pathway may be larger than lesion size produced by ablation at a single site, resulting in multiple RF applications with lengthy sessions and prolonged radiation exposure. Information from both old and recent literature suggests that the slow AV nodal pathway is represented by a group of fibers originating from the posteroinferior interatrial septum and coursing anterosuperiorly near the tricuspid annulus before converging upon the compact AV node. Based on this anatomical arrangement, the present study was conducted to evaluate a technique designed to transect the slow pathway by producing a linear RF lesion perpendicular to the orientation of the slow pathway within the mid-portion of Koch's triangle. Using this technique, 30 of 30 patients with common AV nodal reentry were rendered noninducible using 1 to 3 RF applications. Total procedure time averaged 3.4 +/- 1.1 hours and fluoroscopy time averaged 14.8 +/- 4.6 minutes. As a marker of efficacy, episodic nonsustained atrial tachycardia (NSAT) during RF delivery occurred in 28 of 30 (93%) successful applications. Three patients experienced tachycardia recurrence and were successfully ablated by repeat procedure. Conduction characteristics and refractoriness of the fast pathway were unchanged in 23 of 23 patients reevaluated at a mean of 7.2 weeks postablation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Alzheimer's-disease-related protein in geriatric schizophrenic patients with cognitive impairment.

The authors compared Alz-50 immunoreactivity in the brain tissue of nine cognitively impaired elderly schizophrenic patients and 13 elderly comparison subjects, both without neuritic plaques or neurofibrillary tangles, and 13 patients with Alzheimer's disease. Alz-50 reactivity was absent in the schizophrenic patients, indicating that geriatric, cognitively impaired patients are unlikely to display the pathology of Alzheimer's disease.

Aged↗