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Biomedical subjects

L J Miller

Publications and source records attributed to L J Miller.

264 records · Page 15Linked to original sources

The International Space Station human life sciences experiment implementation process.

The selection, definition, and development phases of a Life Sciences flight research experiment has been consistent throughout the past decade. The implementation process, however, has changed significantly within the past two years. This change is driven primarily by the shift from highly integrated, dedicated research missions on platforms with well defined processes to self contained experiments with stand alone operations on platforms which are being concurrently designed. For experiments manifested on the International Space Station (ISS) and/or on short duration missions, the more modular, streamlined, and independent the individual experiment is, the more likely it is to be successfully implemented before the ISS assembly is completed. During the assembly phase of the ISS, science operations are lower in priority than the construction of the station. After the station has been completed, it is expected that more resources will be available to perform research. The complexity of implementing investigations increases with the logistics needed to perform the experiment. Examples of logistics issues include- hardware unique to the experiment; large up and down mass and volume needs; access to crew and hardware during the ascent or descent phases; maintenance of hardware and supplies with a limited shelf life,- baseline data collection schedules with lengthy sessions or sessions close to the launch or landing; onboard stowage availability, particularly cold stowage; and extensive training where highly proficient skills must be maintained. As the ISS processes become better defined, experiment implementation will meet new challenges due to distributed management, on-orbit resource sharing, and adjustments to crew availability pre- and post-increment.

Biological Science Disciplines↗

Evaluation of nondistended pyriform sinus without respiratory maneuvers.

Detection of a nondistended pyriform sinus on cross-sectional imaging studies represents a diagnostic dilemma. The finding may be an inconstant physiologic phenomenon without clinical significance, or it may be due to tissue thickening and lack of pliability related to neoplasia or inflammation. Rescanning during respiratory maneuvers may clarify the anatomy, but full patient cooperation is needed. We demonstrate a method (turning the patient's head away from the side of the nondistended sinus) that induces distention of the pyriform sinus but does not require active patient participation.

Adult↗

MR angiography of peripheral posterior inferior cerebellar artery aneurysms.

OBJECTIVE: A small subset of posterior inferior cerebellar artery (PICA) aneurysms arise distal to the vertebral artery origin of the PICA. We present two such cases seen on conventional angiography and MR angiography (MRA). MATERIALS AND METHODS: The findings in two patients are presented. In one the aneurysm presented with subarachnoid hemorrhage. The second was found incidentally but later ruptured. RESULTS: There was good agreement between the appearance of the aneurysms on MRA and conventional angiography. CONCLUSION: Awareness of the possibility of peripheral PICA aneurysms and their features is important. The positioning of the volume of excitation for MRA may have to be adjusted to include a very low PICA caudal loop.

Arteries↗

Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update.

The angiotensin converting enzyme (ACE) inhibitors are a group of effective drugs with a unique mechanism of action. These drugs have proven to be useful for hypertension and congestive heart failure. Early clinical trials of captopril used doses that are now known to be inappropriately high, and dose-related adverse effects were observed frequently. The recognition that lower doses are effective has reduced the incidence of adverse reactions and resulted in improved patient tolerance. When patients are properly selected and correctable risk factors are removed, serious side effects are uncommon. Unfortunately, the early reputation of nephrotoxicity persists, as does the belief that significant blood dyscrasias, endocrine effects and rash are serious risks for the average patient. After wide use of captopril, enalapril and lisinopril, and investigational trials of nearly a dozen newer agents, a sufficiency of clinical observation, experimental evidence and accurate postmarketing recording of events is accumulating to allow insight into the major toxicities with regard to more intelligent patient selection, more rational dosing and proper identification of risk factors. The most common adverse reactions are cough and skin rash. It appears that the agents are generally not cross-reactive with regard to skin rash, although it is not clear whether this effect is drug-specific or class-specific with regard to cough. Statistically but not clinically significant lowering of haemoglobin and hematocrit is common; these effects are inconsequential in most patients. Neutropenia, once thought to be prevalent, now appears to be so only in patients with autoimmune or collagen-vascular disease; the majority of patients outside these groups are at low risk. Hyperkalaemia is a frequent occurrence. This should not be surprising in view of the effect of the ACE inhibitors on plasma aldosterone. When dietary potassium intake is regulated and sources of altered potassium excretion are identified, hyperkalaemia is seldom a serious problem. Identification of sodium and water deficits allows correction before the drugs are started, and the frequency of hypotension and hyperkalaemia caused by the drugs is quite low if these factors are properly managed. An unexpected finding emerging in recent years is the dry cough associated with ACE inhibitor therapy. Its mechanism is not definitely known. Nonsteroidal anti-inflammatory drugs may control this symptom in some patients. The frequent observation of proteinuria in patients taking ACE inhibitors has gained notice and sometimes caused undue alarm. It is difficult to separate disease effects in diabetes and hypertension from true drug effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Cytokines in human breast cancer: IL-1alpha and IL-1beta expression.

We hypothesize that interleukin 1alpha (IL-1alpha) and interleukin 1beta (IL-1beta) are present and tumor cell associated in human breast cancer (HBC) specimens. To test our hypothesis: a) immunologic analysis was performed on HBC histologic sections for IL-1alpha (n=49) and IL-1beta (n=42) distribution; and b) homogenates of HBC tumors were analyzed for levels of IL-1alpha (n=82), IL-1beta (n=101) and interleukin 8 (IL-8) (n=103) expression. Immunohistochemical analysis demonstrated the presence of IL-1alpha and IL-1beta in tumor cells in patients with invasive cancer and ductal carcinoma in situ. Quantitative analysis confirmed the presence and positive correlation of IL-1alpha and IL-1beta to IL-8, a known angiogenic factor, in cancer specimens. These studies demonstrate that tumor-associated IL-1alpha+, IL-1beta are present in the tumor microenvironment and may play a pivotal role in regulating breast tumor growth and metastasis.

Breast Diseases↗

Parental hopes for therapy outcomes: children with sensory modulation disorders.

OBJECTIVE: Understanding parents' hopes for therapy outcomes is essential to family-centered care. This qualitative study explored parents' points of view regarding their hopes for the outcomes of occupational therapy using a sensory integration treatment approach. METHOD: Data were collected as part of a larger research project on the effectiveness of rehabilitating children who have sensory modulation disorders. Five interviews were randomly selected from 17 parent interviews conducted in the larger study. Data were analyzed using grounded theory methods. FINDINGS: Three themes pertinent to the occupations of children and two themes related to the occupations of parenting and sustaining family life emerged. Child-focused outcomes include social participation, self-regulation, and perceived competence. Parent-focused outcomes include learning strategies to support children and obtaining personal validation. DISCUSSION: Interventions are proposed that relate to children's participation in contexts in which they live, learn, and play, as well as the support of parents in the occupations of parenting.

Adult↗

Quality improvement in the cutaneous micrographic surgery laboratory.

A nationwide advocacy for improving health-care quality--including the dimensions of efficiency, productivity, and customer satisfaction--is rapidly growing. This initiative is evolving in an environment of total quality management (TQM) and continuous quality improvement (CQI). Quality assessment and improvement (QI) is a quality management program through which laboratories ensure the quality of their health-care services by continually monitoring, evaluating, and resolving opportunities for improvement. Using a systematic, FOCUS-PDCA approach, the Mohs histology laboratory implemented improvement of the quality management of frozen-section slide production and turnaround time (TAT). The Mohs laboratory achieved improved technical process performance, faster TAT time, more efficacious patient care support, and increased customer satisfaction. Using a comprehensive quality assessment and improvement process can overwhelm quality management assets if it is not approached in a systematic, prioritized manner. However, when judiciously used, the process can become a key instrument for ensuring and improving high-quality laboratory services in an efficient manner.

Data Collection↗

The biochemical characterization of the native pancreatic cholecystokinin receptor using affinity labeling approaches.

Affinity labeling has been a powerful tool for the biochemical characterization of sparse molecules which bind to a ligand probe in a specific, high-affinity manner. The rat pancreatic acinar cell receptor for cholecystokinin (CCK), the major physiologic hormonal stimulant of pancreatic exocrine secretion, has been the target of such investigation. Of interest, affinity-labeling studies have identified two distinct plasma membrane glycoproteins as candidates to represent this receptor. The initial candidate, which was identified using 125I-Bolton Hunter-labeled CCK-33 as probe, migrates on a SDS-polyacrylamide gel as a broad band in the M(r) = 80,000 range. Subsequently, using shorter probes in which the site of covalent attachment was closer to the receptor-binding domain of the probe, a band of M(r) = 85,000-95,000 was specifically labeled. Deglycosylation and protease-peptide mapping demonstrated that these bands represent distinct molecules. Using "intrinsic" probes of the receptor, in which a photolabile residue was sited within the pharmacophoric domain of the ligand, attention was focused on the latter candidate as representing the binding protein. Insight into the relationship between these proteins as they reside in the plasma membrane was contributed by labeling with a "topographical mapping" probe, which incorporates a flexible spacer of variable length between a CCK-like ligand and a photolabile residue. This procedure confirmed that these two minor membrane proteins are spatially associated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗

The efficiency of covalent labeling of the pancreatic cholecystokinin receptor using a battery of crosslinkable and photolabile probes.

Affinity labeling is a powerful method for biochemical characterization of hormone receptors, dependent on approximation of reactive groups on ligand and receptor. In this work, we have compared the efficiency of covalent labeling of the rat pancreatic cholecystokinin (CCK) receptor by decapeptide probes with differing photolabile moieties sited at their amino-terminus, mid-region, or carboxyl-terminus, or chemically crosslinkable via their amino-terminus. Each labeled the same M(r) = 85,000-95,000 plasma membrane glycoprotein with a protein core of M(r) = 42,000. Affinity labeling this band through the amino-terminus of the decapeptide, 125I-D-Tyr-Gly [(Nle28,31)CCK-26-33], was inefficient using bifunctional chemical reagents, m-maleimidobenzoyl-N-hydroxy-succinimide ester (0.07% of total incubated radioactivity, representing 0.4% of specifically bound counts) or disuccinimidyl suberate (0.02, 0.2%) or a photolabile carbene precursor (0.06, 0.2%). A benzophenone at this locus yielded more efficient labeling of this band (0.09, 11.8%), but high levels of nonspecific labeling. Probes attached through residues within the receptor-binding domain were particularly useful. Photolabile derivatives of phenylalanine at the carboxyl-terminus of this domain yielded better incorporation (4-nitro-Phe33: 0.23, 1.4%; 4-azido-Phe3: 0.67, 6.0%). A 6-nitro-Trp30 derivative in the middle of this domain gave similarly efficient labeling (0.08, 3.5%) despite being a less potent pancreatic secretagogue. These studies clearly demonstrate that the efficiency of covalent labeling of a receptor can be markedly affected by the nature and site of crosslinking chosen.

Affinity Labels↗

Small intestinal manifestations of diabetes mellitus.

Diabetic diarrhea and steatorrhea occur predominantly in young adult males who have juvenile-onset diabetes mellitus complicated by neuropathy. The presentation is often severe, with nocturnal or postprandial watery diarrhea and tenesmus. Massive malabsorption of fat may occur; however, malabsorption of other nutrients and generalized wasting are quite rare. Because the symptoms are relatively refractory to treatment, it is important to rule out other, more easily treatable causes of this presentation. Bacterial overgrowth, exocrine pancreatic insufficiency, and celiac disease are also associated with diabetes mellitus and can mimic this process. Although the mechanism of diabetic diarrhea and steatorrhea remains unclear, neuropathy, gastrointestinal motor abnormalities, bacterial overgrowth, and bile acid abnormalities have been implicated in the pathogenesis.

Celiac Disease↗

Expression of interleukin-8 receptors on tumor cells and vascular endothelial cells in human breast cancer tissue.

UNLABELLED: Recently, we demonstrated the presence of Interleukin-8 (IL-8) in human breast cancer (HBC) tissue. We hypothesize that the IL-8 receptors are present and play a role in tumor cell and vascular endothelial cell (VEC) activation (e.g. proliferation and angiogenesis). MATERIALS AND METHODS: Immunohistochemical analysis for IL-8 receptors (IL-8RA and IL-8RB) was performed on 43 malignant and 8 benign breast tissue samples. RESULTS: Tumor cells expressed IL-8RA and IL-8RB in all of the malignant specimens. Only 50% of the benign ductal epithelial cell (DEC) samples expressed these receptors. The majority of small vessel endothelial cells (SVEC) expressed IL-8RA and IL-8RB, while large vessel endothelial cells (LVEC) showed primarily IL-8RB expression. CONCLUSIONS: Our results demonstrate that tumor and VEC express the IL-8 receptors and likely play a role in regulating tumor and VEC activation which controls proliferation, angiogenesis and metastasis in HBC.

Antigens, CD↗