Environmental regulation of the development of glucocorticoid receptor systems in the rat forebrain. The role of serotonin.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
D Francis
Publications and source records attributed to D Francis.
Prognostic impact of urokinase, urokinase receptor, and type 1 plasminogen activator inhibitor in squamous and large cell lung cancer tissue.
We have studied the prognostic value of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and type 1 plasminogen activator inhibitor (PAI-1) in tumor extracts from 84 patients with squamous cell lung carcinoma and 38 patients with large cell lung carcinoma, measuring each molecule with sandwich enzyme-linked immunosorbent assays. High uPAR levels were significantly associated with short overall survival in patients with squamous cell lung carcinomas when the median value was used as a cutoff point (P = 0.038), while no statistically significant prognostic impact of uPA and PAI-1 levels was found in this group of patients. The combination of high uPAR and high PAI-1 levels did, however, have a particular significant association with short overall survival (P = 0.008). None of the 3 components was found to have a statistically significant prognostic impact in the group of 38 large cell lung cancer patients. There was a positive correlation between uPAR and PAI-1 levels in both groups and between uPA and uPAR levels in the large cell carcinoma patients. In a multivariate analysis, high uPAR was found to be an independent prognostic variable in squamous cell carcinoma patients, with a relative risk of 2.1 (95% confidence interval, 1.1-4.0) and tumor size the only other significant prognostic parameter. These data suggest that uPAR is an important prognostic factor in squamous cell lung carcinoma. In addition to the potential direct clinical usefulness, this information could be helpful in understanding the biology of this disease and developing new therapeutic approaches.
Aged↗
Urokinase and plasminogen activator inhibitor type 1 in pulmonary adenocarcinoma.
The urokinase pathway of plasminogen activation is involved in proteolytic degradation of various tissues, including dissolution of the extracellular matrix and basement membranes during the process of cancer cell invasion. We have studied the prognostic value of urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAI-1) in tumor extracts from 106 patients with adenocarcinoma of the lung. uPA and PAI-1 levels were determined by sandwich enzyme-linked immunosorbent assays. No correlation was found between uPA and PAI-1 (r = 0.23). High PAI-1 levels were significantly associated with short-duration overall survival (P = 0.017), while uPA levels showed no significant association with overall survival. Relating the levels of PAI-1 to other prognostic factors such as stage and age, no significant correlations were found. The prognostic impact of uPA and PAI-1 were investigated together with other prognostic factors in Cox multivariate analysis. PAI-1 was found to be an independent prognostic variable for survival, the relative risks being 1.5 (low versus medium PAI-1 values (95% confidence interval, 1.2-1.8) and 2.2 (low versus high (95% confidence interval, 1.8-2.6)). In patients with stage I disease (69 patients) high levels of PAI-1 were significantly associated with poor prognosis compared to low levels (P = 0.037). These data indicate that PAI-1 is a potentially important prognostic factor in pulmonary adenocarcinoma and may as such be used to select patients with low stage and poor prognosis for adjuvant therapy subsequent to complete surgical resection.
Adenocarcinoma↗
Seven genes on the short arm of human chromosome 3 map to two regions on Macropus eugenii (tammar wallaby) chromosome 2.
Seven genes were mapped by in situ hybridization to metaphase chromosomes of the marsupial species Macropus eugenii, using a series of human-derived cloned probes (six cosmids and one cDNA). The genes were located in two widely separated clusters on the long arm of M. eugenii chromosome 2, in contrast to their location in a single cluster on the distal half of the short arm of human chromosome 3. Multiple rearrangements had to be involved in the evolutionary divergence of these chromosome segments from the unknown arrangement in the common ancestor.
Animals↗
B-chromosome systems in the greater glider, Petauroides volans (Marsupialia: Pseudocheiridae). II. Investigation of B-chromosome DNA sequences isolated by micromanipulation and PCR.
B chromosomes, despite their common occurrence throughout the animal and plant kingdoms, have not been investigated extensively at the molecular level. While the majority of B chromosomes occurring in animals have been described as heterochromatic, only a few researchers have examined the DNA of these chromosomes beyond this gross cytological level. This is the case in the largest of the gliding marsupial possums, the greater glider, Petauroides volans. To examine the molecular composition and localization of B-chromosome DNA sequences in P. volans, a combination of micromanipulation and the polymerase chain reaction was used in this study to isolate and then amplify the DNA of the B chromosomes. Localization of the isolated B-chromosome sequences to metaphase chromosomes was investigated using fluorescence in situ hybridization. The B chromosomes in this species are shown to be composed of a heterogeneous mixture of sequences, some of which are unique to the B chromosomes, while others exhibit homology to the centromeric regions of the autosomal complement.
Animals↗
Peritoneal mesotheliomas in Danish women: review of histopathologic slides and history of abdominal surgery.
An unexpectedly large number of peritoneal mesotheliomas among women was reported to the Danish Cancer Registry during the years 1960 through 1985. In a case-control study, we tested whether this was due to diagnostic misclassification or to direct exposure of the peritoneal membranes to talc during abdominal surgery. Tissue specimens were available from 96 reported peritoneal mesotheliomas; 35 cases (37%) were regarded as verified mesotheliomas, and 33 (34%) as possible mesotheliomas. Information on any intraabdominal surgery was obtained from the hospital records of these 68 cases and for 206 controls with a cancer of the uterine corpus or pancreas. No association was seen between peritoneal mesotheliomas and abdominal surgery performed more than 25 years prior to cancer diagnosis (odds ratio, 0.83; 95% confidence interval, 0.35-1.94). CONCLUSION. Misclassification of other cancers was the reason for the observed excess of peritoneal mesotheliomas.
Abdomen↗
[2 cases of lymphangioleiomyomatosis treated by hormonal manipulation].
The course of disease in two women with bioptically verified lymphangioleiomyomatosis (LAM) is demonstrated. One was oestrogen- and progesterone-receptor negative, but responded promptly to hysterosalpingo-oophorectomy and has had no symptoms later. The other was receptor positive, but in spite of hysterosalpingo-oophorectomy and hormonal manipulation with tamoxifen and medroxyprogesterone, has had a complicated course of the disease with symptoms for ten years. LAM is a hormone dependent disease, but our knowledge is still incomplete. Hormonal manipulation should be tried in receptor positive as well as negative patients. Tamoxifen seems to have deleterious effects on the course of disease.
Adult↗
Tobacco plants transformed with cdc25, a mitotic inducer gene from fission yeast.
We investigated the effects of expressing a cDNA of cdc25, a mitotic inducer gene of Schizosaccharomyces pombe, on the development of transgenic tobacco plants (Nicotiana tabacum cv. Samsun). Nine independent primary transformants were regenerated containing the cdc25 sequence under the control of a cauliflower mosaic virus 35S gene promoter. Eight of the nine plants showed altered leaf morphology, the lamina being lengthened and twisted and the interveinal regions being pocketed. One of these was sacrificed for analysis of the root meristem, where the cells were found to be significantly smaller than in the wild type. The other seven were grown on and showed precocious flowering, flowers being produced earlier and in significantly greater numbers than in the wild type. They also developed abnormal flowers on short stalks developing in a position normally occupied by the most proximal axillary bud of otherwise normal flower pedicels. The presence or absence of these phenotypes in the primary transformants and in the T2 generation was associated with the presence or absence of detectable levels of cdc25 transcripts.
Base Sequence↗
Molecular basis for the development of individual differences in the hypothalamic-pituitary-adrenal stress response.
1. Several years ago, investigators described the effects of infantile handling on the development of hypothalamic-pituitary-adrenal (HPA) responses to stress in the rat. Rat pups exposed to brief periods of innocuous handling early in life showed reduced HPA responses to a wide variety of stressors, and the effect persists throughout the life of the animal. These effects are robust and provide an excellent model for understanding how early environmental stimuli, which are external to the organism, alter neural differentiation and, thus, neuroendocrine responsivity to stress. 2. This paper reviews the endocrine mechanisms affected by early handling and our current understanding of the neural transduction of environmental events and their effects at the level of the target neurons (in the hippocampus and frontal cortex). 3. In brief, handling serves to increase glucocorticoid receptor gene transcription, increasing sensitivity to glucocorticoid negative feedback regulation and, thus, altering the activity within hypothalamic corticotropin-releasing factor/vasopressin neurons. Together these changes serve to determine neuroendocrine responsivity to stress.
Adrenal Cortex↗
Genetic structure of a natural population of Dictyostelium discoideum, a cellular slime mould.
Dictyostelium discoideum is a eukaryotic microbe feeding on soil bacteria. A first step towards describing the genetic structure of populations of this species was made by examining multiple isolates from a single locale. The isolates were grown clonally and their RFLP patterns compared, using a probe specific for a family of tRNA genes. Thirty-nine types were distinguished in 54 isolates. To determine if genetic exchange occurs among members of the population, an analysis of linkage disequilibrium was performed on the RFLP data. Little disequilibrium was found, implying gene flow in the population. In conflict with this result is the finding that no recombinant progeny were recovered from many attempted crosses between pairs of isolates. The tentative conclusion is that genetic exchange does not in fact occur, and that the observed shuffling of RFLP bands is caused by insertion and excision of transposons known to be associated with the tRNA genes of Dictyostelium.
Animals↗
Activation of central alpha 1-adrenoceptors in humans stimulates secretion of prolactin and TSH, as well as ACTH.
In normal male volunteers, intravenous infusions of the alpha 1-adrenergic agonist methoxamine stimulated the secretion of prolactin, thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH), and the effects were abolished by pretreatment with the alpha 1-antagonist prazosin. To investigate the site of action of methoxamine, its effects were compared with those of equipotent doses of norepinephrine, an alpha 1-agonist that reaches the pituitary gland and the median eminence after an intravenous infusion but, unlike methoxamine, does not cross the blood-brain barrier. Norepinephrine did not stimulate secretion of prolactin, TSH, or ACTH, suggesting that the stimulant alpha 1-adrenoceptors are located in the central nervous system and not directly on the pituitary gland or in the periphery. The alpha 2- and beta-adrenoceptor agonist properties of norepinephrine could not account for the differences from methoxamine, as pretreatment with prazosin did not modify hormone concentrations after norepinephrine. Methoxamine had no behavioral stimulant effects, as judged by visual analog scales that were sensitive to physiological changes in behavioral arousal. In four patients with hypothalamic dysfunction but responsive pituitary corticotrophs, methoxamine had no stimulant effect on the secretion of ACTH, confirming that the alpha 1-adrenoceptors that stimulate ACTH secretion are not located directly on the pituitary. None of the drugs had an effect on the secretion of growth hormone or the gonadotrophins.
Adrenocorticotropic Hormone↗
[Determination of estrogen receptor status in breast cancer by immunocytochemical examination of fine-needle aspirates].
Estrogen receptor status was determined by immunocytochemical examination of fine-needle aspirates in 109 cases of primary invasive breast carcinoma. The results were compared with those from biochemical determination performed on tumor cytosols. Positive agreement was found between qualitative determination (positive/negative) by the two methods in 83% of the cases, and after semiquantitative stratification into three groups the results corresponded in 76%. The predictive value of a positive result on fine-needle aspirate was 96%, and 57% of a negative result. It is concluded that immunocytochemical determination of estrogen receptor status of breast carcinomas on fine-needle aspirate with the applied technique cannot replace the current standard biochemical method.
Aged↗
Plant and organ development.
Explore the source record for details and available documents.
Gene Expression Regulation↗
The evolution of human chromosome 21: evidence from in situ hybridization in marsupials and a monotreme.
We have mapped five human chromosome 21 (HSA 21) markers in marsupials and a monotreme, two major groups of mammals that diverged from eutherians 130-150 and 150-170 million years before present (MYrBP), respectively. We have found that these genes map to two distinct autosomal sites, one containing SOD1/CBR/BCEI and the other containing ETS2/INFAR, in the marsupials Macropus eugenii and Sminthopsis macroura (which belong to orders that diverged 40-80 MYrBP), as well as in the monotreme Ornithorhynchus anatinus (the platypus). Since marsupials and monotremes diverged independently from eutherians, these data suggest that HSA 21 genes were originally located in two separate autosomal blocks. In another Sminthopsis species, SOD1 is linked to TRF (a marker on HSA 3q), suggesting that the ancestral SOD1/CBR/BCEI region also included HSA 3 markers. We suggest that these blocks became fused early in the eutherian evolution to form a HSA 3/21 chromosome, which has remained intact in artiodactyls, but has been independently disrupted in both the primate and rodent lineages.
Animals↗
High frequency jet ventilation: use of the Bain system for entrainment.
The use of a Bain system to convey anaesthetic gases for entrainment during high frequency jet ventilation (HFJV) was evaluated by examining the effect of varying the fresh gas flow (Vf) on the end-tidal carbon dioxide (PECO2) in 46 ASA physical status I and II patients undergoing extracorporeal shock-wave lithotripsy (ESWL). Anaesthesia was induced with methohexitone (1-2 mg.kg-1), fentanyl (1-1.5 micrograms.kg-1) and vecuronium (0.1 mg.kg-1). After endotracheal intubation with a Mallinckrodt Hi-Lo Jet cuffed endotracheal tube, the patient was immersed in a water bath and HFJV at 150 breaths per minute was instituted with an Acutronic AMS 1000 jet ventilator attached to the side channel of the Hi-Lo tube. A Bain system was attached to the proximal end of the endotracheal tube to provide gases for entrainment. Anaesthesia was maintained with an intravenous infusion of methohexitone (5 mg.kg-1.h-1) and 50% nitrous oxide in oxygen for both the jetted and entrained gases. PECO2 was determined at 5-min intervals by a single-breath technique using a calibrated Engstrom Eliza capnograph. Thirty patients were randomly allocated to receive Vf's of 50 (Group 1), 75 (Group 2) and 100 (Group 3) ml.kg-1.min-1, respectively. A further eight patients (Group 4) received a Vf of 100 ml.kg-1.min-1 for 15 min, 75 ml.kg-1.min-1 for the next 15 min and 50 ml.kg-1.min-1 thereafter. In a further group of eight patients (Group 5), Vf was initially 25 ml.kg-1.min-1 for 10 min and was then switched off for the remainder of the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Pulmonary hamartoma.
Eighty-nine cases of pulmonary hamartoma were studied. There were 51 men and 38 women, with a mean age of 57.5 years (range 14 to 76 years). A histologic diagnosis from examination of the resection specimens was obtained in all patients who had operations. Moreover, transthoracic needle aspiration biopsies were performed in 40 patients, with a diagnostic result in 34 (85%). The hamartomas were equally distributed in the pulmonary lobes; mean transverse diameter at the time of diagnosis was 21.7 +/- 16.2 mm. Tumor size was independent of the anatomic localization, but it correlated with the age of the patients (p less than 0.01). Tumor growth was recorded in 15 of 31 patients who had follow-up (45%); mean expansion in transverse diameter was 3.2 +/- 2.6 mm per year during an average observation time of 4.1 years (range 1 to 20 years). Pulmonary symptoms were present in 35 patients (39%). Seventy-five patients underwent operations as follows: enucleation (54), resection (11), lobectomy (5), pneumonectomy (4), and bronchoscopic removal (1). Since most pulmonary hamartomas are nonexpanding or slowly growing neoplasms, it is concluded that operation is necessary only when expansion is recorded in young or middle-aged patients and in patients with pulmonary symptoms.
Adolescent↗
[Flumazenil, hepatic encephalopathy and benzodiazepines].
Explore the source record for details and available documents.
Benzodiazepines↗
Three genes which affect founding of aggregations in Polysphondylium pallidum.
PN6024 is an extraordinary mutant strain of the cellular slime mold Polysphondylium pallidum, characterized by having defects in many unlinked genes. New strains with altered development appeared spontaneously as aberrant clones of PN6024. Genetic crosses using the macrocyst sexual cycle were used to show that PN6030 (a clone like PN6024 in phenotype) carries mutations at two loci, emm and hge, whereas PN6031 (a clone of altered morphology) carries in addition a mutation at a third locus, mgt. hge and possibly mgt are linked to the mating type locus mat. The relatively high frequency of recombination between mat and hge is strong evidence that meiosis precedes macrocyst germination. The mutant genes themselves are of interest. A major effect of the emm-1 mutation is to remove the requirement for light to trigger aggregation. hge-1 greatly reduces the frequency of aggregation, whereas mgt-1 greatly increases it under standard conditions. None of these mutations interrupts later development leading to stalks and spore cells. It is hypothesized that all three genes act on steps immediately preceding the differentiation of the founder cells which initiate aggregation.
Crosses, Genetic↗