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Biomedical subjects

J Allen

Publications and source records attributed to J Allen.

At least 181 records · Page 10Linked to original sources

Anaerobic degradation of polycyclic aromatic hydrocarbons and alkanes in petroleum-contaminated marine harbor sediments.

Although polycyclic aromatic hydrocarbons (PAHs) have usually been found to persist under strict anaerobic conditions, in a previous study an unusual site was found in San Diego Bay in which two PAHs, naphthalene and phenanthrene, were oxidized to carbon dioxide under sulfate-reducing conditions. Further investigations with these sediments revealed that methylnaphthalene, fluorene, and fluoranthene were also anaerobically oxidized to carbon dioxide in these sediments, while pyrene and benzo[a]pyrene were not. Studies with naphthalene indicated that PAH oxidation was sulfate dependent. Incubating the sediments with additional naphthalene for 1 month resulted in a significant increase in the oxidation of [14C]naphthalene. In sediments from a less heavily contaminated site in San diego Bay where PAHs were not readily degraded, naphthalene degradation could be stimulated through inoculation with active PAH-degrading sediments from the most heavily contaminated site. Sediments from the less heavily contaminated site that had been adapted for rapid anaerobic degradation of high concentrations of benzene did not oxidize naphthalene, suggesting that the benzene- and naphthalene-degrading populations were different. When fuels containing complex mixtures of alkanes were added to sediments from the two sites, there was significant degradation in the alkanes. [14C]hexadecane was also anaerobically oxidized to 14CO2 in these sediments. Molybdate, a specific inhibitor of sulfate reduction, inhibited hexadecane oxidation. These results demonstrate that a wide variety of hydrocarbon contaminants can be degraded under sulfate-reducing conditions in hydrocarbon-contaminated sediments, and they suggest that it may be possible to use sulfate reduction rather than aerobic respiration as a treatment strategy for hydrocarbon-contaminated dredged sediments.

Alkanes↗

Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome.

Pallister-Hall syndrome is a human developmental disorder that is inherited in an autosomal dominant pattern. The phenotypic features of the syndrome include hypothalamic hamartoma, polydactyly, imperforate anus, laryngeal clefting, and other anomalies. Here we describe the clinical characterisation of a family with 22 affected members and the genetic mapping of the corresponding locus. Clinical, radiographic, and endoscopic evaluations showed that this disorder is a fully penetrant trait with variable expressivity and low morbidity. By analysing 60 subjects in two families using anonymous STRP markers, we have established linkage to 7p13 by two point analysis with D7S691 resulting in a lod score of 7.0 at theta = 0, near the GLI3 locus. Deletions and translocations in GLI3 are associated with the Greig cephalopolysyndactyly syndrome. Although Greig cephalopolysyndactyly syndrome has some phenotypic overlap with Pallister-Hall syndrome, these two disorders are clinically distinct. The colocalisation of loci for these distinct phenotypes led us to analyse GLI3 for mutations in patients with Pallister-Hall syndrome. We have previously shown GLI3 mutations in two other small, moderately affected families with Pallister-Hall syndrome. The linkage data reported here suggest that these larger, mildly affected families may also have mutations in GLI3.

Abnormalities, Multiple↗

Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas.

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 +/- 6% at 2 years and 68 +/- 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 +/- 11% vs. 75 +/- 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 +/- 7% compared with a rate of 39 +/- 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.

Adolescent↗

Biospheric theory and report on overall Biosphere 2 design and performance.

This article reviews the structural complexity of Biospheres as well as Vernadsky's two laws of biospherics generalized into laws of thermodynamics. The history of designing and building apparatuses to test biospheric hypothesis are summarized: Drs. Shepelev and Gitelson's experiments in Russia, and Space Biospheres Ventures' 10,974 ft3 Test Module and 3.15-acre Biosphere 2 systems. Critical parameters in building Biosphere 2 are outlined: species lists, state descriptors, ecosystems, key variables, closure, and the necessity of observer-managers. Some results of the 2-year Mission One experiment in Biosphere 2 are summarized: human health, light-CO2 coupling, food production, redundancy in maintenance. Change made to the Biosphere 2 system after the first 2-year mission and before the start-up of the second mission are listed. As well, the future of artificial biospheres is considered.

Agriculture↗

Stress and distress in pediatric nurses: lessons from Baby K.

BACKGROUND: Nurses experience stress and suffering when they care for critically ill and dying patients. Moral distress occurs when nurses are unable to translate their moral choices into moral action. In response to this stress, nurses may experience burnout. OBJECTIVE: To investigate the attitudes and perceptions of the nurses who were ordered by the court to provide long-term care for Baby K, a female child with anencephaly. METHOD: A questionnaire was developed to provide descriptive insight into the stress and distress the nurses experienced while caring for Baby K. RESULTS: Nurses caring for Baby K experienced stress and suffering. Although they felt supported and respected as nurses in their workplace, they felt conflict with the legal system. To compensate for feelings of powerlessness, the nurses simply put on a professional face and continued to provide care. They feared making mistakes, many felt guilty and angry, and all felt that they were not included in decision making. CONCLUSIONS: (1) Suffering among caregivers occurs and must be recognized, (2) measures must be taken to reduce the stress and distress of healthcare professionals as they provide care to patients who cannot recover, and (3) in addition to these measures, society must provide guidance to healthcare professionals, especially concerning the care of patients who are permanently unconscious.

Anencephaly↗

Epidermolysis bullosa acquisita associated with epidermal-binding circulating antibodies.

Epidermolysis bullosa acquisita (EBA) is a rare, immunobullous disease, characterized by circulating and tissue-bound antibodies against type VII collagen (C7) of anchoring fibrils in the cutaneous basement membrane zone. These antibodies localize to the dermal aspect of salt-split skin on indirect and direct immunofluorescence (IMF). We report two patients with clinical features of EBA, in whom circulating IgG antibodies bound to the epidermal aspect of salt-split skin. In both patients direct IMF of salt-split perilesional skin revealed dermal IgG deposits, and direct immunogold immunoelectron microscopy showed antibody deposits in the region of anchoring fibrils. Their serum failed to react with epidermal or dermal extracts on Western immunoblotting. Epidermal-binding antibodies have not been reported previously in association with EBA, and the IMF findings in these cases suggest the development of autoantibodies to additional epidermal-associated antigens. Target antigen heterogeneity has been reported in most other immunobullous diseases, and may be a hitherto unrecognized feature of EBA.

Adult↗

The location of binding sites of pemphigus vulgaris and pemphigus foliaceus autoantibodies: a post-embedding immunoelectron microscopic study.

Pemphigus is a life-threatening autoimmune blistering disease of skin and mucous membranes that has two major subtypes based on clinical and histological features, pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Autoantibodies against the PV antigen (desmoglein 3) and the PF antigen (desmoglein 1) are involved in the pathogenesis of blister formation. In the present study, the location of epitopes recognized by autoantibodies of patients with PV and PF was studied by postembedding immunogold electron microscopy. PV and PF autoantibodies were observed bound predominantly to the intercellular domains of desmosomes, but not to the non-desmosomal keratinocyte cell surface. The relationship between the location of PF antigen and other constitutive desmosomal proteins, desmocollin, desmoplakin and plakoglobin, in normal human skin was investigated using a double immunogold labelling technique. It was observed that PF antigen and desmocollin co-localize within the intercellular domain of the desmosomes. In contrast, the antibodies against desmoplakin and plakoglobin bound predominantly to the intracellular desmosomal attachment plaque with the binding site of the antibody against plakoglobin closer to the desmosomal cell membrane than that of the antibody to desmoplakin. We show that the LR White postembedded immunogold electronmicroscopy technique is convenient and easily applied to studies of autoimmune bullous skin diseases. We have used it to demonstrate the precise localization of the binding sites of PV and PF autoantibodies and their relationship with other constitutive desmosomal proteins.

Antigens↗

Pulmonary artery catheterization: a narrative and systematic critique of randomized controlled trials and recommendations for the future.

OBJECTIVE: The purpose of this review is to evaluate the current literature regarding the efficacy of pulmonary artery catheterization, to assess the quality of existing randomized controlled trials and to make recommendations for future studies. DATA SOURCE: A Medline search was conducted of English language studies published between 1970 and 1996 using as search terms "Swan-Ganz catheterization," "pulmonary artery catheterization," and "right heart catheterization." STUDY SELECTION: Randomized controlled trials of pulmonary artery catheterization were selected for review. Sixteen randomized controlled trials were identified. DATA EXTRACTION: The quality of the randomized controlled trials was assessed and a formal meta-analysis was performed. DATA SYNTHESIS: The overall quality score was 40.15 +/- 6.32 out of a possible score of 100. Serious deficiencies were identified including a lack of a priori sample size calculations, unclear definitions of concomitant therapy, inability to blind physicians and patients, and lack of blinded outcome assessments. A random effects model found the relative risk ratio of .808 (95% confidence interval [CI] = .598, 1.091; p = .148). An analysis of potential covariates revealed patients from surgical series treated with pulmonary artery catheter (PAC)-guided therapy had a relative risk ratio of .578 (95% CI = .357, .937; p = .03) compared with control groups. Patients from medical or mixed unit series had a relative risk of 1.043 (95% CI = .784, 1.387; p = NS). CONCLUSION: Existing randomized controlled trials on PAC-guided strategies reveal a modest risk reduction that does reach statistical significance. Risk reduction appears to be greatest in surgical series. Deficiencies of these trials have important implications for the proper design of future trials.

Catheterization, Swan-Ganz↗

Policies regarding the transplantation of hepatitis C-positive candidates and donor organs.

Whether hepatitis C virus (HCV)-positive candidates or donor organs should undergo transplantation remains controversial. Seventy-two thoracic transplantation centers responded to a survey soliciting specific information about policies regarding the listing of HCV-positive candidates and the use of HCV-positive donor organs. Most centers (64%) list HCV-positive candidates for heart transplantation. Twenty-six percent of centers refuse to use HCV-positive organs, whereas the remainder restrict the use of HCV-positive organs to status 1 recipients or HCV-positive candidates. More information is needed regarding the clinical outcomes of HCV-positive candidates and recipients of HCV-positive organs before clear-cut candidate selection and organ allocation policies can be established.

Ethics, Medical↗

Physicochemical characterization and differentiation of the components of the cutaneous basement membrane zone.

Many of the techniques used in the diagnosis and characterization of the acquired blistering diseases of the skin and of their target antigens require the use of tissue that has been modified by heat, chemicals, or by proteolytic digestion. The effect these treatments may have on the blistering disease antigens is poorly understood and has seldom been taken into account in the interpretation of the results. Likewise, their effect on the immunodetection and expression of the ubiquitous proteins of the basement membrane zone and extracellular matrix has rarely been investigated. We have addressed this problem by probing tissue split after heat, chemical treatment and proteolytic digestion with an extensive panel of antibodies to the hemidesmosome-plasma membrane-anchoring filament complex, the extracellular matrix and the anchoring fibrils. The results showed that chemical modification by sodium chloride, calcium chloride and ethylenediaminetetraacetic acid, and incubation in 0.15 mol/L NaCl at 56 degrees C for 1 min did not adversely affect the expression of the alpha 6 beta 4 integrin, laminin-5, the LH39 antigen, laminin-1, collagen type IV or collagen type VII. The methods that involved proteolytic digestion had the greatest detrimental effect on these basement membrane components, with pepsin having a damaging effect on the greatest number of antigens, and the LH39 antigen being the most sensitive to proteolytic degradation. This project has highlighted the susceptibility of the basement membrane zone and extracellular matrix proteins to proteolytic hydrolysis. It has demonstrated a way of differentiating between specific proteins, and has shown its potential for the differential diagnosis of the autoimmune blistering disease antigens.

Antigens, Surface↗

Are retroviruses involved in the aetiology of human breast cancer?

To further investigate the possibility for retroviral involvement in the etiology of human breast cancer we processed peripheral blood monocytes and malignant breast tissue biopsies from 10 patients with breast cancer (infiltrating ductal carcinoma or infiltrating lobular carcinoma; ages 40-80 years) and 20 normal healthy women (with no evidence or family history of breast cancer. 10 age-matched controls and 10 women age 22-27 years) for the assay of the retroviral enzyme, reverse transcriptase, using an ELISA and for election microscopy examination for the detection of retroviral-like particles. Reverse transcriptase activity was detected in 5 out of 10 samples of monocyte culture medium and in 1 out of 10 of malignant tissue biopsies from the patients with breast cancer. In contrast, reverse transcriptase was not detected in the culture medium of the monocytes from any of the control subjects. Electron microscopy did not reveal the presence of any retroviral-like particles in any sample of monocyte culture medium or in any of the malignant or normal breast tissue biopsies. Despite evidence for the presence of reverse transcriptase in a subsample of the monocyte culture medium and breast tissue biopsies from the cohort of breast cancer patients who participated in this study, the role of retroviruses in human breast cancer remains unclear.

Adult↗

Initial studies on active immunization of HIV-infected subjects using a gp120-depleted HIV-1 Immunogen: long-term follow-up.

In 1987, exploratory clinical studies were initiated to determine whether the development of AIDS in HIV-infected individuals might be delayed or prevented by immunization with an inactivated HIV preparation. Preclinical studies had shown the preparation to be safe and immunogenic. Twenty-three patients with biopsy-confirmed persistent generalized lymphadenopathy (CDC III) and two with asymptomatic HIV infection and CD4 lymphocyte counts between 135 and 769/mm3 were studied, of whom eight (32%) had additional HIV-related symptoms. Over a 3-year period, they received a median of eight open-label inoculations of 100 micrograms of inactivated gp 120-depleted HIV-1 Immunogen in incomplete Freund's adjuvant (IFA). Clinical, general laboratory, immunologic, and virologic parameters were followed for up to 6 years. No serious treatment-related adverse experiences were reported, nor was accelerated HIV disease progression seen. Twelve patients developed a delayed-type hypersensitivity response (HIV-DTH) to the immunogen and nine showed fourfold or greater increases in anti-p24 antibody titers. In the follow-up period, 10 of the 25 patients developed AIDS and one with Kaposi's sarcoma (KS) at baseline progressed. Of the 12 patients who became HIV-DTH-responsive, one developed an opportunistic infection (OI), occurring approximately 5 years from study onset, and subsequently died. One additional HIV-DTH responder developed KS. Of the 13 patients who remained HIV-DTH-nonresponsive, nine (69%) progressed to AIDS and seven of these have died. Differences were also observed in terms of HIV-DNA copy number, CD4 percentages, and anti-p24 antibody patterns between the HIV-DTH-responsive and -nonresponsive groups, suggesting a more favorable clinical course in the former. HIV-1 Immunogen in IFA appears to be safe and immunogenic. Further studies are indicated to determine clinical efficacy of the HIV Immunogen as well as the significance of the apparent correlation between HIV-DTH responsivity and a more favorable clinical course.

AIDS Vaccines↗

Differentiated vascular myocytes: are they involved in neointimal formation?

The role of differentiated vascular myocytes are neointimal formation in canine carotid artery was investigated. Using antibodies and cDNA probes, cells were characterized in situ and after isolation. In situ characterization indicated the majority of medial cells expressed both smooth muscle myosin and alpha actin but many cells were negative to these markers. All adventitial cells were negative for these proteins. The muscle protein-positive cells were designated differentiated, vascular myocytes (VSMC). The others were designated type 2 cells. Sequential enzyme digestion from lumenal surface yielded VSMC ( > 90%) while digestions from the adventitial surface yielded type 2 cells ( > 90%). VSMC were viable in culture but did not spread, proliferate, or alter expression of muscle proteins. Type 2 cells proliferated and increased their expression of muscle actin but did not express muscle myosin. Characterization of neointimal cells from injured carotid arteries indicated they were morphologically and immunologically identical to cultured type 2 cells. We concluded that: (a) canine carotid artery media consists of a heterogeneous cell population: (b) serum does not stimulate isolated VSMC to undergo phenotypic modulation or proliferate: and (c) type 2 cells may be responsible for neointimal formation because they proliferate and acquire a phenotype identical to in situ neointimal cells.

Actins↗

Maternal serum interleukin-6 concentrations in patients with preterm premature rupture of membranes and evidence of infection.

OBJECTIVE: Our purpose was to determine whether maternal serum interleukin-6 concentrations are elevated in patients with preterm premature rupture of membranes and intrauterine infection. STUDY DESIGN: By use of a sensitive enzyme-linked immunosorbent assay maternal serum interleukin-6 concentrations were measured in 110 samples from patients at 22 to 34 weeks gestation with the following conditions: nonlaboring, uninfected controls (n = 46), preterm premature rupture of membranes > 48 hours before delivery without infection (n = 27), preterm premature rupture of membranes 24 to 48 hours before delivery with subsequent clinical or histologic infection (n = 11), and preterm premature rupture of membranes < 24 hours before delivery with infection present by clinical or histologic criteria (n = 26). The Mann-Whitney U test was used for statistical analysis. RESULTS: Compared with that of nonlaboring controls, serum interleukin-6 was significantly higher in patients with preterm premature rupture of membranes < 24 hours before delivery with evidence of infection (17.2 vs 1.6 pg/ml, p < 0.0001). Patients with preterm premature rupture of membranes 24 to 48 hours before delivery who had infection had significantly higher interleukin-6 concentrations than did nonlaboring controls (3.6 vs 1.6 pg/ml, p = 0.006). There was no significant difference in interleukin-6 concentrations in nonlaboring controls compared with patients with preterm premature rupture of membranes when serum was obtained > 48 hours before delivery (1.6 vs 1.6 pg/ml, p = 0.90). A serum interleukin-6 level > or = 8 pg/ml yielded a sensitivity of 81%, a specificity of 99%, a positive predictive value of 96%, and a negative predictive value of 95% for identifying intrauterine infection in patients with preterm premature rupture of membranes on the day of delivery. CONCLUSIONS: Maternal serum interleukin-6 concentrations are elevated in patients with preterm premature rupture of membranes with clinical or histologic chorioamnionitis.

Delivery, Obstetric↗