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Biomedical subjects

P Fox

Publications and source records attributed to P Fox.

At least 73 records · Page 4Linked to original sources
PubMed1996

The vesiculo-vacuolar organelle (VVO): a distinct endothelial cell structure that provides a transcellular pathway for macromolecular extravasation.

The vesiculo-vacuolar organelle (VVO) is a recently described organelle found in the cytoplasm of endothelial cells that line tumor microvessels and normal venules. VVOs are grape-like clusters of interconnecting uncoated vesicles and vacuoles, bounded by trilaminar unit membranes, that span the entire thickness of vascular endothelium, thereby providing a potential trans-endothelial connection between the vascular lumen and the extravascular space. Macromolecular tracers preferentially cross hyperpermeable tumor microvessels through VVOs. The present investigation was undertaken to elucidate further the ultrastructure and function of VVOs in a murine ovarian carcinoma (MOT) and in normal venules. Morphometry revealed that VVOs were enormous cytoplasmic structures (median area, 0.12-0.14 microns2 in single electron micrographs). Moreover, the individual vesicles and vacuoles that comprised VVOs were on average substantially larger than capillary caveolae and followed a non-normal distribution that was skewed to the right. Specimen tilting provided conclusive evidence that individual VVO vesicles and vacuoles communicated with each other and with the endothelial cells' plasma membranes by stomata, some of which were closed by diaphragms composed of a single membrane. Studies with two tracers, ferritin (FE, diameter approximately 11 nm) and horseradish peroxidase (HRP, diameter approximately 5 nm), revealed that passage of macromolecules through VVOs was regulated at the level of stomatal diaphragms, thereby demonstrating a mechanism for controlling the passage of macromolecules across endothelial cells. Thus, compared with tumor microvessels, little circulating FE and HRP entered the VVOs of normal venular endothelium because stomata joining vesicles and vacuoles to each other and to the lumen and ablumen were closed. VVOs and their component vesicles/vacuoles were readily distinguished from endosomal organelles such as coated vesicles and multivesicular bodies, which also accumulated FE and HRP. Our findings indicate that VVOs provide a major pathway for the extravasation of circulating macromolecules across endothelia taller than capillary endothelium and suggest that upregulated VVO function accounts for the well-known hyperpermeability of tumor blood vessels.

Animals↗
PubMed1996

Recovery of human basophils after FMLP-stimulated secretion.

BACKGROUND: Basophils are circulating, secretory granulocytes that are generally considered to be end-stage cells. In one species of guinea-pigs, basophilic leucocytes have been shown to recover from stimulated secretion in short-term cultures. Similar studies have not been done using human basophils. OBJECTIVE: The purpose of this study was to examine human basophils in short-term recovery intervals following stimulation of secretion to determine whether visual evidence of recovery occurred. METHODS: We examined the ultrastructural morphology of early recovery (10 min-6 h) of human basophils following secretion stimulated by formyl-methionyl-leucyl-phenyl-alanine (FMLP). A combined technique for electron microscopy consisted of post-fixation exposure to cationized ferritin and reduced osmium, providing maximum quality images and allowing identification of intracellular spaces/organelles that opened to the cell surface, often out of the plane of section. RESULTS: The ultrastructural evaluation revealed that control basophils (0 time-6 h) did not undergo regulated secretion or develop the morphologies associated with recovery following secretion. FMLP-stimulated basophils underwent an overlapping continuum of piecemeal degranulation-->anaphylactic degranulation (0 time-1 min), producing vesicle- and granule-free, completely degranulated, viable, mature basophils with polylobed nuclei. The early recovery period (10 min-6 h) following FMLP stimulation was characterized by reconstitution of granules. Morphological mechanisms for granule reconstitution included a mixture of conservation, condensation, and synthetic events. CONCLUSION: Human basophils, like guinea pig basophils, have the potential to recover from regulated secretion.

Basophils↗
PubMed1996

The economic costs of cardiovascular disease mortality in California, 1991: implications for public health policy.

This study estimates costs of lost productivity in California due to cardiovascular disease (CVD) mortality. Death records were used to calculate mortality losses including the number of deaths due to CVD, Years of Potential Life Lost (YPLL), and the value of productivity losses. In 1991 there was $5.3 billion in lost productivity due to mortality caused by diseases of the heart and over one billion dollars in lost productivity due to cerebrovascular disease mortality. Racial/ethnic differences in YPLL are pronounced, which likely reflect the long-standing inverse association between CVD mortality and socioeconomic status that has been documented in a variety of populations worldwide. While it is important to effectively retain or develop low risk behaviors in populations, it is equally important to reduce barriers engendered by social, economic, and political patterns that inhibit the compression of CVD morbidity and mortality.

Aged↗
PubMed1995

Protein concentration by precipitation with pyrogallol red prior to electrophoresis.

The pyrogallol red protein assay (Clinical Chemistry 1986, 32, 1551-1554) is based upon formation of a blue protein-dye complex in the presence of molybdate under acidic conditions. However, centrifugation of the assay mixture results in loss of color yield and precipitation of the protein-dye complex which can be recovered and resolubilized to achieve protein concentration prior to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The method has been evaluated relative to trichloroacetic acid (TCA) precipitation for recovery and electrophoresis of commercial protein and peptide molecular weight markers. Precipitation with pyrogallol red-molybdate (PRM) gives better and more uniform recovery of both proteins and peptides as compared to TCA. The lower limit of PRM precipitation is similar to TCA and corresponds to 1 microgram protein per mL assay mixture. This is equivalent to 100 microL of 10 micrograms/mL protein using the standard protein assay or 1 microgram/mL protein using a modified assay incorporating a fivefold concentrate of the dye reagent. Application of the method is demonstrated by concentration of urinary proteins. The method is simple and economic and useful for conserving trace amounts of precious sample as it allows recovery of protein for electrophoresis following protein assay.

Chemical Precipitation↗
PubMed1995

Alzheimer's disease. The unpaid burden of caring.

This study presents detailed estimates of the hours and cost of informal care provided to Alzheimer's disease patients in Northern California. Data were collected over 12 months from 93 community-residing patients and their caregivers and from 94 institutionalized patients and their caregivers. Patients residing in the community received an average of 286 hours per month of unpaid care, whereas institutionalized patients received 36 hours per month. Alternative methods of imputing informal costs are described. The annual value of informal care (in 1990 dollars) is $34,517 for the noninstitutionalized sample and $5,542 for the institutionalized sample. The determinants of informal caregiving were examined and compared in the two settings. The more cognitively impaired the individual, the higher the informal costs no matter what the residential setting. In an institutional setting, the younger the patient and caregiver, the higher the costs. If a caregiver is not a spouse, higher informal care costs were also found.

Alzheimer Disease↗
PubMed1995

Use of covered services in Medicare home health care.

Using data on 295 patients entering Medicare home health care at discharge from Medicare hospital stays, we explain receipt of Medicare home health nursing, PT and OT visits, and length of stay. Care reflected need, but other factors also affected service allocation. Medicare program requirements, as well as variation in provider structure and case load, appear to introduce inequities. Critical in light of recurrent proposals to change Medicare coverage and benefits, findings underline the need to reconsider Medicare home health policies that lead to denial of needed services, inequitable allocation of benefits, and premature termination of care.

Aged↗
PubMed1994

Examination of the use of smoking for weight control in restrained and unrestrained eaters.

Recent research has examined the perceived benefits of smoking and suggests that continued smoking may be related to contemporary concerns for weight and shape. The present study examined the role of restrained eating in predicting smoking for reasons of weight control, reports of weight gain following cessation, and reasons for relapse and intentions to quit. Eighty-four restrained eaters and 83 unrestrained eaters completed a questionnaire examining their smoking behavior. The results suggest that the restrained eaters gave significantly greater endorsement than the unrestrained eaters to statements relating to smoking initiation and smoking maintenance for weight control, the role of weight gain in previous experiences of smoking relapse, intentions to quit following weight loss, and intentions to quit in 5 years. No differences were found between the restrained and unrestrained eaters in terms of experiences of post cessation weight gain, the number of attempts to quit, and intentions to quit in 6 months. The results are discussed in terms of developing a model of the relationship between smoking and weight concerns.

Adolescent↗
PubMed1994

Living alone with Alzheimer's disease: effects on health and social service utilization patterns.

Subjects with possible or probable Alzheimer's disease who live alone are more likely to be women, and more likely to be poor than those living with others. They are also older and have milder cognitive impairments and a shorter disease duration. Living arrangement is a significant predictor of service utilization even with other factors held constant. Subjects living alone were less likely to use medical services such as physicians and hospitals, and more likely to use services such as homemaker chore and home-delivered meals. In addition, they were more likely to use no services than those living with others.

Activities of Daily Living↗
PubMed1994

Identification and characterization of a gene cluster mediating enteroaggregative Escherichia coli aggregative adherence fimbria I biogenesis.

The aggregative pattern of adherence (AA) exhibited by enteroaggregative Escherichia coli upon HEp-2 cells is a plasmid-associated property which correlates with aggregative adherence fimbria I (AAF/I) expression and human erythrocyte hemagglutination. By using cloning and mutagenesis strategies, two noncontiguous plasmid segments (designated regions 1 and 2) required for AA expression have previously been identified in enteroaggregative E. coli 17-2. TnphoA mutagenesis was performed on clones containing region 1, and 16 TnphoA mutants which were negative for the AA phenotype were analyzed. The TnphoA insertion site for each mutant was determined by junctional DNA sequencing. All 16 mutations occurred within a 4.6-kb span in region 1. Nucleotide sequence analysis of the region revealed four contiguous open reading frames, designated aggDCBA, in the same span. AA-negative TnphoA insertions into all open reading frames except aggB were obtained. On the basis of mutational analysis and protein homology data, it is inferred that aggA, aggC, and aggD are involved in biogenesis of AAF/I, encoding a major fimbrial subunit, outer membrane usher, and periplasmic fimbrial chaperone, respectively. By immunogold electron microscopy, polyclonal antiserum raised against the aggA gene product decorated AAF/I fimbriae, affirming that AggA encodes an AAF/I subunit.

Bacterial Adhesion↗
PubMed1992

Implications for expressed emotion therapy within a family therapeutic context.

Expressed emotion instruments measure variant levels of criticism, blaming, and anger within families of mentally ill people. Some theorists believe that high levels of expressed emotion predispose schizophrenic patients for relapse. However, recent trends in family therapy indicate that high expressed emotion may naturally result from caring for an ill family member. Families may therefore often feel unfairly blamed by practitioners for causing mental illness. The author examines the usefulness of integrating expressed emotion measures into family therapy from three theoretical perspectives: the transactional perspective, the coping and adaptation perspective, and the systems perspective. Each of these perspectives provides a framework for incorporating expressed emotion measures into the broader context of research on and treatment of schizophrenia. The author postulates that appropriate controls designed to reduce pent-up emotion in families must accompany expressed emotion interventions in family therapy. Appropriate controls might include exercise, meditation, spiritual focus, or membership in a support group.

Adaptation, Psychological↗
PubMed1991

A randomized clinical trial of scatter photocoagulation of proliferative sickle cell retinopathy.

A randomized prospective clinical trial of argon laser scatter photocoagulation therapy for proliferative sickle cell retinopathy was performed on 116 patients (174 eyes) in Kingston, Jamaica. Ninety-nine eyes were treated with scatter photocoagulation and 75 eyes served as controls. The average length of follow-up was 42 months for the control eyes and 47 months for the treated eyes. Prolonged loss of visual acuity was statistically significantly reduced in the treated eyes. The incidence of vitreous hemorrhage was also significantly reduced in the treated eyes after controlling for the previously defined risk factors of vitreous hemorrhage and extent of proliferative sickle cell retinopathy at entry into the study. There were no complications associated with argon laser scatter photocoagulation. Scatter photocoagulation of proliferative sickle cell retinopathy is currently the most effective and safe way to treat patients with sea fan neovascularization.

Adult↗
PubMed1990

Batch tests to determine activity distribution and kinetic parameters for acetate utilization in expanded-bed anaerobic reactors.

Batch tests to measure maximum acetate utilization rates were used to determine the distribution of acetate utilizers in expanded-bed sand and expanded-bed granular activated carbon (GAC) reactors. The reactors were fed a mixture of acetate and 3-ethylphenol, and they contained the same predominant aceticlastic methanogen, Methanothrix sp. Batch tests were performed both on the entire reactor contents and with media removed from the reactors. Results indicated that activity was evenly distributed within the GAC reactors, whereas in the sand reactor a sludge blanket on top of the sand bed contained approximately 50% of the activity. The Monod half-velocity constant (K(s)) for the acetate-utilizing methanogens in two expanded-bed GAC reactors was searched for by combining steady-state results with batch test data. All parameters necessary to develop a model with Monod kinetics were experimentally determined except for K(s). However, K(s) was a function of the effluent 3-ethylphenol concentration, and batch test results demonstrated that maximum acetate utilization rates were not a function of the effluent 3-ethylphenol concentration. Addition of a competitive inhibition term into the Monod expression predicted the dependence of K(s) on the effluent 3-ethylphenol concentration. A two-parameter search determined a K(s) of 8.99 mg of acetate per liter and a K(i) of 2.41 mg of 3-ethylphenol per liter. Model predictions were in agreement with experimental observations for all effluent 3-ethylphenol concentrations. Batch tests measured the activity for a specific substrate and determined the distribution of activity in the reactor. The use of steady-state data in conjunction with batch test results reduced the number of unknown kinetic parameters and thereby reduced the uncertainty in the results and the assumptions made.

Journal Article↗
PubMed1989

From senility to Alzheimer's disease: the rise of the Alzheimer's disease movement.

Alzheimer's disease, once a rarely applied medical diagnosis, is now considered to be the fourth or fifth leading cause of death in the United States. Several interrelated factors account for the disease's ascendancy as the preferred category to characterize specific types of neuropsychiatric problems associated with aging. These include a shift in the disease's conceptualization, the emergence of an institutional structure facilitating increased awareness of the disease, and the growth of a constituency advocating greater spending for and expansion of research on the disorder. A biological phenomenon was transformed into a social issue when persons took concerted action to promote Alzheimer's disease as a major social and health problem affecting the elderly.

Aged↗