Two cases of fish mortality in low pH, aluminium rich water.
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Alum Compounds↗
Biomedical subjects
M Ingram
Publications and source records attributed to M Ingram.
The histopathology of Candida albicans invasion in neonatal rat tissues and in the human blood-brain barrier in culture revealed by light, scanning, transmission and immunoelectron microscopy.
The present studies examined the effects of Candida albicans yeast and hyphal morphologies on tissue pathologies and transmigration properties of the fungus in two experimental models: 1) an in vivo, neonatal rat model, and 2) a cell culture model of human brain microvascular endothelial cells (ECs) (BMVEC). We inoculated a hyphae-producing strain (CAI4-URA3) and a non-hyphae-producing strain (CAI4) of C. albicans into 4-10 day old rats and BMVEC cultures. Animals were inoculated by intraperitonal (i.p.), intranasal (i.n.), oral (p.o.) and intracerebral (i.c.) routes and several tissues were examined after 24-48 hrs. Rats inoculated i.p. with the hyphae-producing strain showed pathology in the kidneys, liver, spleen, and other tissues associated with inoculation tracks of the nose, and muscle and connective tissues of the abdominal wall. Few animals inoculated i.p., however, presented evidence of meningitis. The non-hyphae phase yeast produced neither tissue pathology nor meningitis. Animals inoculated i.c. with the hyphae strain after 1 and 3 hrs expressed minimal meningitis, with an increasing neutrophillic meningitis between 4 and 18 hrs after inoculation. At 18 hrs after i.c. inoculation, however, the inflammatory foci and brain pathology were extensive and demonstrated mycelia within the lateral ventricles associated with necrosis of adjacent brain tissue. Neutrophillic meningitis at this time period was pronounced. BMVEC co-cultured 1-2 hrs with both C. albicans strains showed EC phagocytosis of hyphae and blastospores into intercellular adhesion molecule-1 (ICAM-1)-labeled caveolae suggesting a transcellular role for ICAM-1 in the internalization process of C. albicans.
Animals↗
Glucocorticoids contribute to the heritability of leptin in Scottish adult female twins.
OBJECTIVE: The precise interactions between glucocorticoids and leptin are complex and poorly understood. The aim of the study was to investigate whether the glucocorticoid/leptin interaction is influenced by shared environmental or genetic factors. DESIGN: We investigated the heritability of body mass index (BMI), circulating leptin and urinary glucocorticoid metabolites [tetrahydrocortisol (THF), alloTHF and tetrahydrocortisone (THE)] in 54 monozygotic (MZ) and 39 dizygotic (DZ) female twins. Analysis was performed using a structural equation modelling package Mx, developed by Neale. RESULTS: Leptin and BMI showed substantial heritability (68.3% and 71.3%, respectively). Bivariate analysis indicated that the genetic determinants of BMI and leptin are partly shared. Total cortisol metabolites (THF + alloTHF + THE), the (THE + alloTHF)/THE ratio [a marker of 11beta-hydroxysteroid dehydrogenase (11HSD) activity] and the alloTHF/THF ratio (marker for 5alpha-reductase activity) followed an environmental pattern. The heritability of leptin was significantly lowered to 63.8% (P = 0.012) when values were corrected for the influence of total cortisol metabolites but unaffected by markers of 11HSD and 5alpha-reductase activity. CONCLUSIONS: We confirm that the genetic influence on both BMI and the circulating leptin concentration is substantial and show that these genetic determinants are highly correlated. These genetic factors, which are more likely to be dominant than additive, can be modestly but significantly modified by urinary total cortisol metabolites implying an adrenal influence.
Adult↗
The structure of anxiety symptoms among preschoolers.
This study examined whether anxiety symptoms in preschoolers reflect subtypes of anxiety consistent with current diagnostic classification systems, or should be better regarded as representing a single dimension. Parents of a large community sample of preschoolers aged 2.5 to 6.5 years rated the frequency with which their children experienced a wide range of anxiety problems. Exploratory factor analysis indicated four or five factors and it was unclear whether separation anxiety and generalized anxiety represented discrete factors. Results of confirmatory factor analyses indicated a superior fit for a five-correlated-factor model, reflecting areas of social phobia, separation anxiety, generalized anxiety, obsessive-compulsive disorder and fears of physical injury, broadly consistent with DSM-IV diagnostic categories. A high level of covariation was found between factors, which could be explained by a single, higher order model, in which first order factors of anxiety subtypes loaded upon a factor of anxiety in general. No significant differences were found in prevalence of anxiety symptoms across genders. Symptoms of PTSD in this sample were rare.
Anxiety↗
Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases.
The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.
Animals↗
Smoking behavior in a smoking workplace.
PURPOSE: This report addresses whether smoking increases as a function of working in a smoking environment. METHODS: Casino employees were targeted to complete a survey designed to assess smoking behavior. The survey contained standardized questions consistent with other major surveys on tobacco use to ensure comparability with state and national trends. Data collection occurred between September and November 1997. RESULTS: Out of 755 surveys distributed, 587 completed surveys were returned, resulting in a response rate of 77 percent. A test of proportions showed that the proportion of smokers had not changed significantly as a result of working in a smoking environment although the amount of smoking decreased significantly (one-sample t-test). The change in the amount of smoking was assessed using difference scores. Males and females did not differ in the rate in which their smoking changed. A significant correlation between age and the change score suggested that younger smokers were more likely to increase their intake whereas the older smoking employees were more likely to decrease their consumption by the time of the survey. IMPLICATIONS: The finding that individuals who work in a smoking environment decreased their smoking behavior merits further investigation in the area of smoking aversion.
Adolescent↗
Lymphocytic infiltration of bladder after local cellular immunotherapy.
BACKGROUND: This is a case report of a patient who received cellular immunotherapy, in the form of local injections of autologous stimulated lymphocytes (ASL) into individual tumors in the urinary bladder. A major consideration in cellular immunotherapy being the ability of immune cells to reach all target areas, we hypothesized that direct delivery of effector cells into individual bladder tumors might assure such access. METHODS: ASL were generated by exposing the patient's PBL to phytohemagglutinin and culturing them in the presence of IL-2 to expand the population. ASL were injected into the base of individual bladder tumors three times at intervals of 3 weeks. RESULTS: The patient died of a myocardial infarct, unrelated to cell therapy, 20 days after the third injection. An autopsy was performed. Histological sections of the bladder showed extensive lymphocytic infiltration of virtually the entire organ. DISCUSSION: No conclusions about the therapeutic efficacy of local immunotherapy using ASL are possible. Nevertheless, the observations reported, taken together with reports of therapeutic efficacy of other immunotherapy regimens in the management of bladder cancer, suggest that ready access of stimulated lymphocytes to all regions of the organ may account, in part, for the relatively high rate of therapeutic success reported for various immunotherapy regimens for this malignancy.
Aged↗
First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx).
PURPOSE: This Phase I study was designed to evaluate the computed tomography (CT) scanner as a device for radiation therapy of human brain tumors (CTRx). This first use in humans of a modified CT for treatment was founded on extensive research experience with canine tumors. An additional objective was to increase the therapeutic radiation dose to tumors compared to normal tissue by concentration of infused contrast material in tumors, an effect available at diagnostic x-ray energies but not at megavoltage energies. METHODS AND MATERIALS: A small metastatic brain tumor in each of eight patients received 3-5-weekly fractions of 5 Gy equivalent per fraction from a CT scanner modified to deliver radiation therapy. In each patient, one additional tumor, lying completely outside the volume treated by CTRx, served as a control. The tumor receiving CTRx was treated after infusion of iodinated x-ray contrast media (CM) for dose enhancement. Many of these patients also received conventional 40 Gy whole brain radiation, before, during, or after CTRx treatment. RESULTS: None of the patients showed adverse reactions to the CM or necrosis of the normal brain from the CTRx boost radiation. Monte Carlo calculations of the radiation dose distributions in a model tumor showed that the CTRx irradiation of tumors carrying 10 mg or more of iodine per gram of tumor was as good or better than the dose distribution from conventional 10-MV X-rays. The treated tumor in two of the patients vanished after four treatments, whereas a control tumor in one patient remained constant and grew 4-fold in another patient. CONCLUSION: The CTRx concept effectively combines a modified CT scanner as a diagnostic device, as a simulator dedicated to radiotherapy, and as a treatment machine. Thus, CTRx could be very useful for radiation oncologists in controlling CM-enhanced and other small brain tumors.
Brain Neoplasms↗
Mechanism of acquired thymic tolerance induced by a single major histocompatibility complex class I peptide with the dominant epitope: differential analysis of regulatory cytokines in the lymphoid and intragraft compartments.
BACKGROUND: We have recently shown that intrathymic injection of a combination of immunogenic WAG-derived or Wistar-Furth (WF) (RT1.Au) major histocompatibility complex class I peptides induces acquired systemic tolerance to cardiac and islet allografts in the WF-to-ACI rat combination and therefore hypothesized that identification of the class I peptide dominance may play an important role in the induction of antigen (Ag)-specific tolerance. This study defined the peptide with the dominant epitope among the seven synthetic RT1.Au peptides and analyzed the immunoregulatory cytokines within the lymphoid and intragraft compartments associated with acquired thymic tolerance. METHODS: ACI recipients were pretreated with intrathymic (IT) injection of 300 microg of the individual seven RT1.Au peptides 7 days before WF or Lewis cardiac transplantation. Cytokine profile of mixed lymphocyte reaction supernatants of T cells obtained from the thymus, mesenteric lymph nodes, spleen, peripheral blood leukocytes, and graft infiltrating cells after donor (WF) or third-party (Lewis) Ag stimulation were measured by enzyme-linked immunosorbent assay, whereas cytokine gene expression was determined by reverse transcription-polymerase chain reaction. RESULTS: Only IT injection of peptide 5 (93-109) among the seven RT1.Au peptides induced donor-spe cific tolerance to cardiac allografts in the WF-to-ACI rat combination. In addition, intravenous injection of peptide 5 did not prolong WF graft survival in ACI recipients. Analysis of cytokine production by the tolerant recipients showed significant Ag-specific reduction in the production of interleukin (IL)-2 and interferon-gamma (IFN-gamma) in the thymus, mesenteric lymph nodes, spleen, and peripheral blood leukocytes, which was not associated with a concomitant Ag-specific increase in IL-4 and IL-10 production. Measurement of cytokine mRNA expression confirmed undetectable
Animals↗
Pathological angiogenesis in a murine model of human Wilms' tumor.
BACKGROUND/PURPOSE: Pathological vascular architecture is a feature of neoangiogenic processes such as diseases of the retina and tumor growth. The authors hypothesized that experimental human Wilms' tumors would display a vascular architecture similar to retinal diseases that are driven by vascular endothelial growth factor (VEGF). METHODS: Human Wilms' tumors were established in the right kidneys of nude mice. After 4.5 weeks of tumor growth, fluorescein angiograms were performed before death. Representative sections of tumors and contralateral, control kidneys were evaluated by fluorescent microscopy. RESULTS: Fluorescein angiograms demonstrated a characteristic pathological architecture. Vascular tortuosity, capillary tufting, and hemorrhage were noted. These features were not present in normal kidneys. CONCLUSIONS: Vascular architecture of Wilms' tumor displays the specific features previously described in diseases of the retina, which have been shown to be driven by VEGF, suggesting that neoangiogenesis in this model is also VEGF driven.
Animals↗
Comorbid affective disorders and personality traits in alcohol abuse inpatients at an Air Force Medical Center.
A retrospective chart review of 2 years of admissions (1995-1996) for alcohol abuse and alcohol dependence patients on an inpatient substance abuse unit showed the prevalence of comorbid affective disorders, personality disorders/subsyndromal personality traits, and the combination of all three diagnoses to be 8.2, 17.5, and 9.6%, respectively. The available literature on these additional diagnoses in substance abusers is reviewed and compared with the findings of the current study. Patients identified for inpatient substance abuse treatment need full psychiatric evaluation for other Axis I and Axis II comorbidity that may greatly affect their treatment plans and clinical prognoses.
Adult↗
X-ray phototherapy for solid tumors.
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Animals↗
The birds and the bees and the plants.
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Animal Population Groups↗
A prospective randomized study of calcium alginate (Sorbsan) versus standard gauze packing following haemorrhoidectomy.
Post-haemorrhoidectomy pain is problematical but may be reduced by using less bulky haemostatic dressings in the anal canal. Fifty consecutive patients undergoing haemorrhoidectomy were prospectively randomized to receive either paraffin gauze/cotton gauze roll on calcium alginate (Sorbsan) roll as a post-operative pack. Post-operative pain was assessed at 6 h, on removal of rectal packing and at first bowel action. Haemorrhage was monitored at 6 h and removal of pack. There was no difference in the hospital stay between the two groups. Pain was significantly reduced at the time of removal/spontaneous discharge of rectal packing (P < 0.0001) and first post-operative bowel action (P = 0.0008) in the calcium alginate group. There was no significant difference in post-operative haemorrhage between the two groups. Calcium alginate dressings following haemorrhoidectomy effectively reduce post-operative pain compared to more bulky anal packs.
Alginates↗
Russian doctors protest over state of nation's health.
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Delivery of Health Care↗
Russia fears rapid increase in HIV infection.
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HIV Infections↗
X-ray phototherapy for canine brain masses.
Brain masses diagnosed in 47 pet dogs as tumors by CT scans, and confirmed in 12 dogs by necropsies, were injected with iodinated contrast media and treated by a modified CT scanner, the CTRx. Twenty-six dogs that received six or more weekly treatments of about 5.6 Gy per fraction, of which about 25% was contributed by radiation from the iodine, for a median total dose of 39 Gy, had a median survival of 230 days. This compares well with the 150 days reported for 25 dogs given 46-48 Gy of cobalt-60 radiation to the whole brain, and is significantly greater than the 6 to 13 days in untreated historic controls.
Animals↗
Three-dimensional growth patterns of various human tumor cell lines in simulated microgravity of a NASA bioreactor.
Growth patterns of a number of human tumor cell lines that from three-dimensional structures of various architectures when cultured without carrier beads in a NASA rotary cell culture system are described and illustrated. The culture system, which was designed to mimic microgravity, maintained cells in suspension under very low-shear stress throughout culture. Spheroid (particulate) production occurred within a few hours after culture was started, and spheroids increased in size by cell division and fusion of small spheroids, usually stabilizing at a spheroid diameter of about 0.5 mm. Architecture of spheroids varied with cell type. Cellular interactions that occurred in spheroids resulted in conformation and shape changes of cells, and some cell lines produced complex, epithelial-like architectures. Expression of the cell adhesion molecules, CD44 and E cadherin, was upregulated in the three-dimensional constructs. Coculture of fibroblast spheroids with PC3 prostate cancer cells induced tenascin expression by the fibroblasts underlying the adherent prostate epithelial cells. Invasion of the fibroblast spheroids by the malignant epithelium was also demonstrated.
Bioreactors↗