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Biomedical subjects

D Francis

Publications and source records attributed to D Francis.

At least 73 records · Page 4Linked to original sources
PubMed1997

Norepinephrine induced growth and expression of virulence associated factors in enterotoxigenic and enterohemorrhagic strains of Escherichia coli.

The small intestine is richly innervated by the sympathetic nervous system. High concentrations of monoamines, most notably norepinephrine, are found throughout the various intestinal layers. In order to determine whether norepinephrine is capable of influencing bacterial pathogenesis, the growth and production of virulence factors in ETEC and EHEC were examined in a physiologically relevant medium utilizing very low initial bacterial inoculums to more closely mimie in vivo conditions. The growth of ETEC strain B44 and the production of the K99 pilus adhesin on a protein equivalent basis was greatly increased in the presence of norepinephrine. Growth of EHEC O157:H7 was also increased in norepinephrine containing medium as well as production of SLT-I and SLT-II. The ability of norepinephrine to increase both bacterial growth and expression of virulence factors was shown to be non-nutritional in nature. Given the abundant adrenergic innervation in the small intestine, these in vitro results suggest that the neurohumoral environment of the host may play a role in bacterial growth and expression of virulence factors.

Antigens, Surface↗
PubMed1997

Lectin staining of renal tubules in normal kidney.

Lectins are glycoproteins able to bind carbohydrate structures specifically. In this study we applied six different lectins on normal renal tissue to investigate their specificity for different segments of the renal tubular system. The following lectins were used: jacalin, peanut agglutinin (PNA), wheat germ agglutinin (WGA), phytohemagglutinin E (PHA-E), concanavalin A (Con A), and Dolichos biflorus agglutinin (DBA). Particular attention was paid to jacalin lectin as its staining properties respecting the renal tubular system were not known. We showed that jacalin lectin strongly stains the luminal border of distal tubules, as well as single cells of the collecting tubules. As regards the other five lectins, PNA stained distal tubules, WGA the whole nephron, PHA-E proximal tubules, and Con A and DBA a few cells of the loop of Henle.

Humans↗
PubMed1996

The prevalence of gentamicin 2'-N-acetyltransferase in the Proteeae and its role in the O-acetylation of peptidoglycan.

The prevalence of aac(2')-Ia, a gene coding for gentamicin 2'-N-acetyltransferase in Providencia stuartii, among species of the Proteeae was investigated to determine if it is a common resistance factor and whether the correlation observed in P. stuartii between its expression and the levels of peptidoglycan O-acetylation represents a general feature of bacteria producing this form of modified peptidoglycan. An evaluation of the MICs of gentamicin for each of the species of the Proteeae did not reveal any apparent relationship between resistance and the degree of O-acetylation of peptidoglycan. The entire aac(2')-Ia gene was used as a probe in Southern hybridization experiments against genomic DNA from each species of the Proteeae. A sequence with strong homology to aac(2')-Ia was present only in Proteus penneri while weak hybridization was also observed to the restriction digested DNA from Providencia rettgeri. Other bacteria that O-acetylate peptidoglycan were also screened with this probe and a homologous DNA sequence was only found in Neisseria subflava. These data suggest that AAC(2')-Ia may contribute to the O-acetylation of peptidoglycan in P. stuartii, but a more specific enzyme must also be produced for this function.

Acetylation↗
PubMed1996

Evolution of promoter sequences: elements of a canonical promoter for prespore genes of Dictyostelium.

An attempt is made to define a minimal prespore promoter which contains all elements essential for correct regulation of expression of a prespore gene. The prespore genes of Dictyostelium are coregulated during development. Most begin transcription at the same early stage, and activity of all is restricted to prespore tissue during the later slug stage. Sequences 5' to the coding sequences of eight prespore genes were searched for all elements proposed to control transcription and for new elements. The meaningfulness of occurrences of elements and pairs of elements in prespore promoters was evaluated by comparison with frequencies of occurrences in promoters of other, nonprespore genes. These comparisons resulted in definition of a canonical prespore promoter, a stretch of about 200 nucleotides containing at least one of each of three elements. Certain limitations were found on the spacing of elements. Orientation of elements with respect to each other appeared unrestricted. All elements often occurred in multiple copies. This structure suggests that individual copies of each element are not conserved during evolution, but instead continually appear and disappear.

Animals↗
PubMed1996

Quality perceptions of microbiology services. A survey of infectious diseases specialists.

Opinions about the quality of their primary microbiology laboratory were received from more than 500 practicing infectious diseases specialists by a nationally distributed questionnaire. Approximately 92% of the respondents' primary laboratories were hospital-based. These sophisticated users rated the quality of their microbiology laboratories to be generally high, with bacteriology receiving highest scores and parasitology the lowest scores. Fortunately, the serious problems, such as failing to call a critical result and culture mishandled in the laboratory, were experienced rarely. Laboratories directed by pathologists with specialty microbiology training, PHD microbiologists, and infectious diseases specialists were judged to be of highest quality. American Board of Medical Microbiology certification of the laboratory director was related to higher overall quality perceptions. Whereas physician-customer opinions may not directly measure a laboratory's analytic quality, they are an important performance measure on which laboratories can base quality improvement activities in both service and analytical aspects of performance.

Clinical Laboratory Techniques↗
PubMed1996

Histo-blood group antigens in human fetal thymus and in thymomas.

The glycosylation of epithelial cell surface antigens follows cellular differentiation, and changes in the pattern of expression are seen in various premalignant and malignant epithelial lesions. The distribution of type-2 chain ABH-carbohydrate structures (N-acetyl-lactosamine, H-type 2 chain, Le-y, Le-x and sialyl-Le-x) of the ABO-histo-blood group system was investigated in 19 normal fetal thymuses (gestational age 16 to 39 weeks) and in 19 thymomas in order to study possible tumor-associated changes in the glycosylation pattern. The material was investigated by immunochemical stainings of formalin-fixed paraffin-imbedded tissue using monoclonal antibodies with defined specificity. In fetal thymus the epithelial cells of the medulla and the Hassal's bodies strongly expressed elongated carbohydrate structures (Le-y, Le-x and sialyl-Le-x). In a few cases the cortical epithelial cells weakly expressed Le-x and sialyl-Le-x. Compared with fetal thymus 16 of the thymomas showed a total loss, or a very much reduced expression of elongated carbohydrate structures. Three thymomas, which histologically had been reclassified according to Kirchner & Müller-Hermelink (14) as high grade thymic carcinomas, revealed strong expression of Le-y, moderate expression of Le-x and weak expression of sialyl-Le-x. This is of interest as in other tumors Le-y is correlated with increased cell motility and with poor prognosis.

ABO Blood-Group System↗
PubMed1996

Lectin staining of renal cell tumours with special emphasis on oncocytomas.

There are conflicting results respecting the segmental tubular origin of renal oncocytomas, a type of tumour said to be highly differentiated and benign, though metastases have been described. The aim of this study was, by applying different lectins on renal cell carcinomas (n = 50) and oncocytomas (n = 12), to search for patterns which could indicate a specific segmental origin of oncocytomas and perhaps elucidate the differentiation of this tumour. The following lectins were applied: jacalin, peanut agglutinin (PNA), wheat germ agglutinin (WGA), phytohemagglutinin E (PHA-E), concanavalin A (Con A), and Dolichos biflorus agglutinin (DBA). The results show that oncocytomas are positive when jacalin, a Lectin that stains distal tubules and collecting tubules, is used, supporting the view that the tumour derives from distal or collecting tubules. The staining of the oncocytomas is generally polarized as in normal kidney tubules underlining that the tumour is highly differentiated. Two oncocytomas with aggressive behaviour showed areas with a diffuse pattern suggesting lower differentiation.

Adenoma, Oxyphilic↗
PubMed1996

Infectious disease physicians rate microbiology services and practices.

Recent years have seen increasing emphasis on cost containment and quality improvement in clinical laboratory activities. Modifying those activities to enhance clinical relevance is one strategy that should be satisfying to both laboratory scientists and administrators. This guest commentary describes one approach to quality improvement--the use of user surveys to identify areas for improvement. As an initial attempt to define such areas in clinical diagnostic microbiology, infectious disease specialists, targeted for their particular interest and expertise in microbiology laboratory results, were polled and their responses were analyzed. Some of these data have been presented previously (E. J. Baron, D. P. Francis, and K. M. Peddecord, abstr. C-170, p. 520, in Abstracts of the 94th General Meeting of the American Society for Microbiology, 1994; K. M. Peddecord, E. J. Baron, D. P. Francis, and A. S. Benenson, abstr. C-172, p. 520, in Abstracts of the 94th General Meeting of the American Society for Microbiology, 1994; K. M. Peddecord, E. J. Baron, D. P. Francis, and J. A. Drew, Am. J. Clin. Pathol. 105:58-64, 1996). The discussion includes our recommendations for the use of these survey responses, and their limitations, as stimuli to initiate reexamination of certain microbiology laboratory practices in the interest of developing more cost-effective and clinically relevant protocols.

Bacteremia↗
PubMed1996

Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress.

The adrenal glucocorticoids and catecholamines comprise a frontline of defense for mammalian species under conditions which threaten homeostasis (conditions commonly referred to as stress). Glucocorticoids represent the end product of the hypothalamic-pituitary-adrenal (HPA) axis and along with the catecholamines serve to mobilize the production and distribution of energy substrates during stress. The increased secretion of pituitary-adrenal hormones in response to stress is stimulated by the release of corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) from neurons in the nucleus paraventricularis. In this way, a neural signal associated with the stressor is transduced into a set of endocrine and sympathetic responses. The development of the HPA response to stressful stimuli is altered by early environmental events. Animals exposed to short periods of infantile stimulation or handling show decreased HPA responsivity to stress, whereas maternal separation, physical trauma and endotoxin administration enhance HPA responsivity to stress. In all cases, these effects persist throughout the life of the animal and are accompanied by increased hypothalamic levels of the mRNAs for CRH and often AVP. The inhibitory regulation of the synthesis for these ACTH releasing factors is achieved, in part, through a negative feedback loop whereby circulating glucocorticoids act at various neural sites to decrease CRH and AVP gene expression. Such inhibitory effects are initiated via an interaction between the adrenal steroid and an intracellular receptor (either the mineralocorticoid or glucocorticoid receptor). We have found that these early environmental manipulations regulate glucocorticoid receptor gene expression in the hippocampus and frontal cortex, regions that have been strongly implicated as sites for negative-feedback regulation of CRH and AVP synthesis. When the differences in glucocorticoid receptor density are transiently reversed, so too are those in HPA responses to stress. Taken together, our findings indicate that the early postnatal environment alters the differentiation of hippocampal neurons. This effect involves an altered rate of glucocorticoid receptor gene expression, resulting in changes in the sensitivity of the system to the inhibitory effects of glucocorticoids on the synthesis of CRH and AVP in hypothalamic neurons. Changes in CRH and AVP levels, in turn, determine the responsivity of the axis to subsequent stressors; increased releasing factor production is associated with increased HPA responses to stress. Thus, the early environment can contribute substantially to the development of stable individual differences in HPA responsivity to stressful stimuli. These data provide examples of early environmental programming of neural systems. One major objective of our research is to understand how such programming occurs within the brain.

Adrenal Cortex↗
PubMed1996

Immunocytochemical localisation of tumor necrosis factor alpha in thyroid tissues from patients with neoplastic or autoimmune thyroid disorders.

It is disputed to what extent tumor necrosis factor-alpha is present in the thyroid follicular epithelial cells and/or in the interstitial cells in different disorders of the thyroid gland. We describe the immunohistochemical detection of tumor necrosis factor-alpha using formaldehyde fixed and paraffin embedded tissue and a polyclonal anti-serum with high tumor necrosis factor-alpha neutralising activity. We examined the distribution of tumor necrosis factor-alpha in interstitial cells and follicular epithelial cells in thyroid carcinomas, adenomas, non-toxic multinodular goiters and autoimmune thyroid diseases. Tumor necrosis factor-alpha was demonstrated in thyroid follicular epithelial cells, most frequently in non-toxic multinodular goiters (six of seven patients) and less frequently in adenomas (three of nine patients), papillary carcinomas (two of five patients), follicular carcinomas (one of five patients), Hashimoto's disease (one of six patients) and Grave's disease (one of seven patients). Tumor necrosis factor-alpha producing interstitial cells were found in two thirds of patients with all six thyroid diseases.

Adenocarcinoma, Follicular↗
PubMed1996

p53 protein in non-small cell lung cancer as quantitated by enzyme-linked immunosorbent assay: relation to prognosis.

The prognostic value of p53 protein in tumor extracts as measured by ELISA was studied retrospectively in 228 non-small cell lung cancer (NSCLC) patients. The assay measures both wild-type and mutated p53. The specimens on which this study was performed have been used earlier to analyze the prognostic impact of components of the plasminogen activation system, which enabled an analysis of relationships between these components and p53 protein. The median of the p53 protein values in the 228 patients was 0.10 (range, 0-0.70) ng/mg protein. Survival analysis comparing patients with p53 levels below versus above the median showed no significant difference (P = 0.67). When analyzing the histological types, adenocarcinoma (n = 106), squamous cell carcinoma (n = 84), and large cell carcinoma of the lung (n = 38) separately, similarly, no significant differences in survival between patients having low versus high tumor p53 levels were found. When comparing levels of p53 protein in the three histological types, a significant difference (P < 0.0001) was found, with adenocarcinomas having the lowest levels. There was a weak positive correlation (r = 0.22) between p53 protein and plasminogen activator inhibitor type 1 (PAI-1). Multivariate analysis proved no impact of p53 on survival; tumor size, PAI-1, and lymph node involvement were the only variables with significant influence on survival. These data indicate that p53 protein quantitated with a sandwich ELISA in tumor extracts from NSCLC has no prognostic value, but the observed statistically significant difference of p53 protein content between histological subgroups may be related to differences in etiology and biology in different NSCLC subtypes. In addition, the weak association found between p53 protein and the independent prognostic marker PAI-1 could suggest yet undefined interactions in lung cancer.

Adult↗
PubMed1995

Effects of adrenalectomy and corticosterone replacement on glucocorticoid receptor levels in rat brain tissue: a comparison between western blotting and receptor binding assays.

A sensitive Western blotting technique, using a commercially available antibody, was developed herein to study glucocorticoid receptor (GR) autoregulation in brain tissue. A prominent immunoreactive band at approximately 94 kDa, representing the GR, was observed in soluble fractions prepared from rat hippocampus whereas two bands (approximately 97 and 94 kDa) were detected in frontal cortex preparations. Four-day adrenalectomy significantly increased immunoreactive GR levels in both brain regions. In contrast, adrenalectomized animals implanted with corticosterone pellets of varying concentrations displayed dose-dependent decreases in immunodetectable GR levels. Radioligand binding assays ([3H]dexamethasone +/- RU 28362), performed on these same tissue preparations, revealed a similar pattern of GR response to that measured by Western blotting. However, changes in GR binding capacity were generally greater in magnitude than corresponding changes in immunoreactive GR levels. This discrepancy was most pronounced in adrenalectomized animals administered a bolus of corticosterone 1 h prior to sacrifice where a 60-70% reduction in receptor binding sites occurred, in sharp contrast to the 25-30% decrease in immunoreactive GR levels. Taken together, our findings suggest that Western blotting can be used to study GR regulation in brain tissue and that changes in steroid-binding capacity may not necessarily reflect changes in receptor protein levels.

Adrenalectomy↗
PubMed1995

The effects of zinc on cell viability and on mitochondrial structure in contrasting cultivars of Festuca rubra L. - a rapid test for zinc tolerance.

A 20-min exposure to 5.0 microg Zn cm(-3) reduced the percentage of viable root meristematic cells in three cultivars of Festuca rubra L.: Merlin (Zn-tolerant), Hawk (salt-tolerant but with a degree of Zn tolerance) and S59 (Zn-sensitive). The Zn-induced cell mortality in S59 was approximately twice that of the tolerant cultivars. The mean area of mitochondrial profiles in root meristematic cells of Zn-untreated roots was similar in S59 and Merlin but that of Hawk was smaller. A 4-day exposure to 0.2 microg Zn cm(-3) resulted in mitochondrial swelling in the Zn-sensitive cultivar; there was a 25% increase in the mean area of mitochondrial profiles in this cultivar, but no significant increase occurred in Hawk or Merlin. Zn treatment caused a collapse of the cristae and a localized condensation of the mitochondrial matrix in S59, but not in Hawk or Merlin. The marked increase in cell mortality after only a 20-min Zn exposure and the relative simplicity of the technique, indicates that this procedure could be used as a rapid and independent measure of Zn tolerance.

Journal Article↗
PubMed1995

Immunocytochemical localisation of interleukin-1 alpha and interleukin-6 in thyroid tissues from patients with neoplastic or autoimmune thyroid disorders.

We describe the distribution of interleukin-6 and interleukin-1 alpha in thyroid tissues obtained from patients with autoimmune diseases or neoplastic thyroid disorders employing immunohistochemistry in sections from paraffin embedded tissue blocks. Interleukin-6 was found in thyroid follicular epithelial cells (TFEC) from papillary carcinomas (four of five patients) but not in follicular carcinomas (five patients). Interleukin-6 was also detected in non-toxic multinodular goiters (four of seven patients), in patients with Graves' disease who did not have an early recurrence of hyperthyroidism after surgery (three of four patients), in follicular adenomas (five of nine patients), in Hashimoto's thyroiditis (two out of six patients, both belonging to a group of three with an early stage of the disease), and in paraadenomatous tissues (in three of nine patients). Interleukin-1 alpha positive TFEC were found less frequently than interleukin-6, and only in tissues with interleukin-6 positive TFEC. Only few interleukin-6 and interleukin-1 alpha positive interstitial cells were found, even in the lymphocyte infiltrates (in both the autoimmune, benign or malignant disorders). In conclusion, both interleukin-6 and interleukin-1 alpha could be demonstrated in TFEC from patients with autoimmune diseases, benign neoplasms or papillary carcinoma, whereas follicular cancer tissues were without interleukin-6 and interleukin-1 alpha. In contrast with previous studies, interleukin-6 and interleukin-1 alpha were demonstrated in TFEC from patients with both Graves' disease and Hashimoto's thyroiditis, and the presence of these cytokines was related to the stage of the autoimmune process.

Adenoma↗
PubMed1995

Thymomas and thymic carcinomas. A retrospective investigation with histological reclassification.

The morphological heterogeneity of thymomas has caused much confusion respecting their classification. Recently Kirchner & Müller-Hermelink (4) proposed a histological subclassification which has been claimed to represent an independent prognostic factor: medullary and mixed thymomas are benign; organoid and cortical type as well as well-differentiated thymic carcinomas are low-grade malignant tumors, which have the capacity to recur and spread, even if they are clinically benign. High-grade malignant thymomas are always malignant. We present the clinicopathological data on 10 clinically benign and 14 clinically malignant thymomas. Having reclassified the thymomas, we found four low-grade malignant examples among the clinically benign thymomas. It is important to identify this group of patients as they are at risk of tumor recurrence. However, further investigation is needed to support the validity of this subclassification system.

Aged↗
PubMed1994

Alterations in central catecholamines associated with immune responding in adult and aged mice.

Central catecholamine alterations associated with immune activity are similar to those seen following stressor exposure. Inasmuch as aged animals exhibit more pronounced stressor-provoked alterations of central amines relative to younger animals, it was of interest to determine whether immune challenge would similarly induce more pronounced central amine variations in older animals. Fifteen-month old CD-1 mice challenged with 10(7) sheep red blood cells (SRBC) revealed an equivalent peak splenic plaque-forming cell response (4 days after antigen challenge) to that of 3-month-old mice challenged with 10(6) cells. Neither plasma adrenocorticotropic hormone (ACTH) nor corticosterone levels varied over days following immunization, although ACTH levels were generally higher in the older mice. In both age groups reductions of hypothalamic and locus coeruleus norepinephrine (NE) and increased accumulation of the metabolite MHPG coincided with (or preceded by 24 h) the peak immune response. However, increased accumulation of MHPG in the hypothalamus was greater and occurred earlier in the locus coeruleus of the aged mice. Likewise, at or about the time of peak immune responses nucleus accumbens dopamine (DA) levels were reduced and metabolites elevated in both age groups, while in the prefrontal cortex only DA metabolite levels were elevated. These data are commensurate with previous findings showing that SRBC inoculation may influence central neurotransmitters and that such effects correspond with the time of the peak immune responses. Moreover, in so far as hypothalamic NE utilization is concerned, it seems that the effects of SRBC inoculation are more pronounced in aged animals.

Adrenocorticotropic Hormone↗