Heterogeneity of growth hormone production in human pituitary tumour cells.
Explore the source record for details and available documents.
Adenoma↗
Biomedical subjects
J R Davis
Publications and source records attributed to J R Davis.
Role of solid media when used in conjunction with the BACTEC system for mycobacterial isolation and identification.
This study evaluated the necessity and the contribution of solid media when used in conjunction with radiometric Middlebrook 7H12 (BACTEC 12B; Becton Dickinson, Towson, Md.) medium for recovery and complete identification of mycobacteria. Each of 1,184 digested, decontaminated respiratory specimens was inoculated into one BACTEC 12B vial, one 7H11 plate, and two Lowenstein-Jensen (LJ) slants. When the 12B vial was smear positive for acid-fast bacilli, the organisms were subcultured onto LJ slants and the BACTEC p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) test system was inoculated with the organisms. Niacin tests were performed by using the growth from the original LJ slants and organisms from the LJ slants subcultured from 12B or 7H11 medium. The times to achieve definitive NAP and niacin test results were recorded. Recovery of all 143 isolates found in this study could not be achieved with a single medium. Among the three media, the highest percentage (92.8%) of Mycobacterium tuberculosis isolate recovered was with BACTEC 12B. The use of either 7H11 medium or LJ slants along with a 12B vial increased by 4 to 6% the total percentage of M. tuberculosis organisms that were isolated. Isolation of the M. tuberculosis complex and NAP differentiation in 12B medium were completed in an average of 17 days. On average, isolation and definitive niacin test results for M. tuberculosis cultures were obtained in 39.3 days by a conventional procedure and in 36.3 days when 12B subcultures were used. These results support the conclusion that LJ slants contribute 4 to 6% increased recovery of M. tuberculosis when used in conjunction with 12B medium. Additionally, a subculture onto LJ slants from 12B medium yielded sufficient growth for niacin testing earlier than an original LJ slant did.
Bacteriological Techniques↗
Calcium/calmodulin regulation of the rat prolactin gene is conferred by the proximal enhancer region.
The effects of the calcium/calmodulin signaling system on expression of the rat PRL gene were studied in rat pituitary GH3 cells using two specific naphthalene sulfonamide calmodulin (CaM) antagonist drugs, W7 and a more potent and more highly specific iodo-derivative, 5-iodo-1-C8. PRL (but not GH) mRNA accumulation was markedly inhibited by W7, which in coincubations abolished the stimulation normally seen with TRH. Transient transfection assays showed that expression of the reporter gene chloramphenicol acetyl transferase (CAT) linked to 5'-flanking sequences from the PRL gene was inhibited by the calcium-channel blocker verapamil and by the two CaM antagonists. The calcium effects showed partial promoter specificity, in that transcription of PRL-CAT constructs was markedly inhibited by verapamil, but the Rous sarcoma virus-CAT construct also showed significant inhibition, whereas the pBL-CAT2 construct was unaffected. Three hundred ninety five base pairs were sufficient to confer the full inhibitory effect of calcium channel blockade or CaM antagonist seen with longer constructs. The data indicate that CaM is important for PRL gene transcription, and that the effects of CaM are exerted on DNA sequences within the proximal 395bp of prolactin 5'-flanking DNA.
Animals↗
Pit-1 binding sequences permit calcium regulation of human prolactin gene expression.
This study examines the regulation of the human PRL (hPRL) gene promoter by intracellular calcium. Deletants of the 5'-flanking region of the hPRL gene and constructs consisting of the thymidine kinase promoter linked to the first or second proximal Pit-1 binding site were fused to the bacterial chloramphenicol acetyl transferase (CAT) reporter gene. With the complete 5-kilobase pair (kbp) hPRL promoter sequence the calcium channel agonist Bay K8644 induced a significant 2-fold increase in CAT reporter gene expression and the antagonist verapamil a 4.5-fold reduction, using GH3 cells cultured in physiological levels of calcium. The transcriptional response to calcium influx was similar with a series of 5'-deleted hPRL-CAT constructs including those that comprised the proximal (up to 740 bp) or distal (-1300- to -1700-bp) sequences alone. When treating cells cultured in low calcium conditions the induction with the hPRL promoter increased to 5-fold on the addition of exogenous calcium and Bay K8644. The pituitary-specific expression of the hPRL gene is conferred by the interaction of the pituitary-specific factor Pit-1 with several binding sites located in the 5'-flanking DNA, of which three are located in the proximal region. This suggested that Pit-1 binding sites may be involved in the calcium response.(ABSTRACT TRUNCATED AT 250 WORDS)
Aminoquinolines↗
Physical activity on the job and cancer in Missouri.
We conducted a series of case-control studies to investigate the risks of 16 cancer types in relation to occupational physical activity. These studies were based on Missouri Cancer Registry data for 17,147 White male cancer patients registered between 1984 and 1989. Colon cancer risk was increased for both the moderate (odds ratio (OR) = 1.1; 95% confidence interval (CI) = 1.0, 1.3) and low (OR = 1.2; 95% CI = 1.0, 1.5) activity levels. Similar elevations were observed for prostate cancer at the moderate (OR = 1.1; 95% CI = 1.0, 1.3) and low (OR = 1.5; 95% CI = 1.2, 1.8) levels of activity, and for cancer of the testis at the low activity level (OR = 2.2; 95% CI = 1.3, 3.7). An opposite trend (p less than 0.01) was noted for lung cancer, which showed decreased risk at the moderate (OR = 0.9; 95% CI = 0.8, 1.0) and low (OR = 0.8; 95% CI = 0.6, 0.9) activity levels. These associations suggest that further study of the relationship between physical activity and site-specific cancer risk is warranted.
Case-Control Studies↗
Effects of epidermal growth factor on growth response, morphology, and invasive potential of human endometrial carcinoma cell line RL95-2.
Exposure of RL95-2 human endometrial adenosquamous carcinoma cells of early passage (less than 30 passages) and late passage (greater than 250 passages) to epidermal growth factor (EGF) resulted in density- and concentration-dependent effects. At low seeding density, EGF (20 nM) inhibited the growth of early passage cells, whereas at high seeding density, 4.98 nM and 20 nM concentrations of EGF stimulated their growth. Furthermore, the growth of late passage cells was stimulated by 0.0166 nM EGF and inhibited by 4.98 nM and 20 nM EGF at both seeding densities. EGF (20 nM) caused marked morphological changes of both passages at the low seeding density. Inhibition of invasion of both passages through Matrigel-coated filters was seen at low seeding density, while at the high seeding density, EGF enhanced invasiveness. At high seeding density, EGF stimulated an increase in urokinase type plasminogen activator activity, which may have augmented the ability of cells to degrade the extracellular matrix. In addition, the ability of high seeding density cells of both passages to adhere to matrigel after EGF treatment correlated with invasiveness.
Adenocarcinoma↗
Quantitation of Plasmodium falciparum sporozoites transmitted in vitro by experimentally infected Anopheles gambiae and Anopheles stephensi.
The frequency and numbers of Plasmodium falciparum sporozoites transmitted in vitro and corresponding sporozoite loads were determined for experimentally infected Anopheles gambiae and An. stephensi. Geometric mean (GM) sporozoite loads in three experiments ranged from 808 to 13, 905 for An. gambiae and from 6, 608 to 17, 702 for An. stephensi. A total of 44.1% of 68 infected An. gambiae and 49.2% of 63 infected An. stephensi transmitted sporozoites in vitro. The GM number of sporozoites transmitted was 4.5 for An. gambiae and 5.4 for An. stephensi. Overall, 86.9% of the mosquitoes transmitted from one to 25 sporozoites, and only 6.6% transmitted over 100 sporozoites (maximum = 369). Sporozoite loads were not a useful predictor of potential sporozoite transmission. Despite higher sporozoite loads, the numbers of sporozoites transmitted in vitro by the experimentally infected mosquitoes were similar to estimates obtained, using the same techniques, for naturally infected An. gambiae in western Kenya. The low but highly variable numbers of sporozoites transmitted in vitro by mosquitoes used in malaria vaccine challenge studies appears to be a reasonable simulation of natural sporozoite transmission.
Animals↗
Hematopathologic features of Epstein-Barr virus-induced human B-lymphoproliferation in mice with severe combined immunodeficiency. A model of lymphoproliferative diseases in immunocompromised patients.
The anatomical distribution, morphology, and clonality, of 'non-Hodgkin's lymphomas' in immunocompromised patients are usually distinctly different from NHL occurring in the general population. Mosier DE, Gulizia RJ, Baird SM, Wilson DB: Nature (London) 335:256, 1988 have described lymphoproliferative disease (LPD) of human B cell origin in mice with severe combined immunodeficiency (scid mice) after transfer of human peripheral blood mononuclear cells from Epstein-Barr virus-seropositive individuals. Reported herein is detailed information regarding the morphology, phenotypes, and clonality of LPD lesions in 10 of 18 scid mice that had developed LPD after transfer of peripheral blood mononuclear cells. These lesions were diffuse and monomorphic proliferations of immunoblastoid cells. They were invasive in their growth and often necrotic. Human B cell-related and activation-associated antigens were found on the LPD lesions, although the numbers of cells with the latter antigens were relatively small. Immunofixation electrophoresis for human immunoglobulins in sera of the majority of mice revealed oligoclonal populations, however, phenotypic and cytogenetic analyses showed no definite monoclonality. This scid mouse model is beneficial for understanding the early phases in the pathogenesis of LPD in immunocompromised patients.
Animals↗
Relation of cytogenetic abnormalities and clinical outcome in metastatic melanoma.
The value of chromosomal analysis is well established in human hematologic neoplasms. In contrast, the relation between chromosomal abnormalities and clinical outcome in solid tumors in humans has received little study. We undertook this study to determine whether chromosomal abnormalities could provide information on the survival of patients with malignant melanoma. Chromosome-banding analysis was performed on tumor-biopsy samples from 62 patients with metastatic melanoma, and recurring cytogenetic abnormalities were correlated with survival. Patients with structural abnormalities of chromosome 7 or 11 had significantly shorter survival than patients without these abnormalities. We conclude that cytogenetic analysis may provide useful prognostic information about patients with metastatic melanoma.
Chromosome Aberrations↗
Differential cellular susceptibility to Epstein-Barr virus infection in a patient with X-linked lymphoproliferative disease.
Epstein-Barr virus (EBV) is often associated with lethal lymphoproliferative diseases in immunologically compromised individuals. Recently, we have studied a 20-month-old boy with X-linked lymphoproliferative disease (XLP) who had succumbed to infectious mononucleosis (IM) complicated by fulminant hepatitis and virus-associated hemophagocytic syndrome following EBV infection. EBV genomes were detected in peripheral blood lymphocytes (PBL), cervical and mesenteric lymph nodes, liver, spleen, thymus, and bone marrow. According to restriction endonuclease analyses, the EBV-DNA pattern was similar in all samples except for the EBV-DNA from the bone marrow. Additionally, circular EBV-DNA (suggesting a latent infection) predominated in spontaneously established lymphoblastoid cell lines (LCLs) derived from both the lymph node and cord lymphocytes co-cultured with PBL. In contrast, both circular and linear EBV-DNA (suggesting a lytic infection) were noted in spontaneously established LCLs derived from his PBL. Furthermore, LCLs derived from both the lymph node and cord lymphocytes co-cultured with PBL expressed fewer reactive cells for early antigen (EA) and viral capsid antigen (VCA) than spontaneous LCLs from his PBL, thus providing evidence for different B cellular susceptibility to EBV infection in this patient with XLP. Finally, defective EBV-specific cytotoxic T cell activity was observed in this patient. Latent EBV infected cells may easily escape immunosurveillance by the host. These findings may explain the fatal course of EBV infection in this patient.
Antigens, Viral↗
Prolactin and related peptides in pregnancy.
This brief review has attempted to portray the complex involvement of prolactin in pregnancy. Pituitary prolactin production and lactotroph proliferation are markedly affected by oestrogens and pregnancy. Enlargement of pre-existing prolactinomas may occur during pregnancy induced with dopamine agonist drugs, and this can be a major clinical problem with larger tumours. Prolactin is produced by late luteal and decidualized endometrium as well as by the pituitary gland, but much less is known about its secretory regulation or its function. The family of prolactin-related protein hormones is rapidly expanding with the recognition of placental lactogens, variant growth hormone, proliferin, decidual luteotropin, and at least two further prolactin-related peptides in rodents. This complex system of related but distinct protein hormones, with different temporal patterns of production during gestation, suggests an important physiological role, but it remains to be seen to what extent they are involved in placental function itself, maternal metabolism or fetal growth.
Animals↗
Myogenic tone of the rat testicular subcapsular artery has a role in autoregulation of testicular blood supply.
An in vitro method is described for the isolation, cannulation, and pressurization of a 10-mm segment of the adult rat testicular subcapsular artery by use of a 200-microns micropipette connected to an adjustable-height reservoir. External and internal arterial diameters were measured by a digital filar micrometer eyepiece calibrated with a Microcode scaler. Transmural pressure was increased stepwise by 20 mm Hg from 20 to 180 mm Hg at 10-min intervals. The following novel triphasic myogenic response was found: a 22.5% increase in lumen cross-sectional area from 20 to 40 mm Hg (p less than 0.05); a 37.3% decrease in lumen cross-sectional area from 40 to 100 mm Hg (p less than 0.05); and a 72.4% increase in lumen cross-sectional area from 100 to 180 mm Hg (p less than 0.05). Papaverine (0.1 mM) completely blocked the transmural pressure-induced vasoconstriction, indicating an active increase in vascular smooth muscle tone by transmural pressure. The calculated blood flow through the testicular subcapsular artery of the adult rat, from measured internal radii at various transmural pressures ranging from 20 to 180 mm Hg by Poiseuille's equation, was constant from 40 to 100 mm Hg and showed a progressive increase from 100 to 180 mm Hg. These data suggest that the myogenic response of the adult rat testicular subcapsular artery may have an important role in the autoregulation of the testicular blood supply.
Animals↗
Continuation of chloroquine-susceptible Plasmodium falciparum parasitemia in volunteers receiving chloroquine therapy.
Volunteers infected with a chloroquine-susceptible line of Plasmodium falciparum were administered standard oral chloroquine therapy at the first detection of parasites in the blood. Parasitemias progressed in the face of therapy for up to 5 days and to levels up to 100-fold greater than those at the initiation of treatment. Thereafter, infections cleared without a requirement for additional chemotherapy. This course of infection and response to treatment has not been previously reported and may have been detected because volunteers were exposed to an unusually large number of sporozoites. The observations are consistent with the hypothesis that prolonged parasitemia resulted from the continued release of merozoites from liver.
Administration, Oral↗
Rapid presumptive identification of gram-negative rods directly from blood cultures by simple enzymatic tests.
Gram-negative rods were presumptively identified directly from blood cultures within 15 min as Escherichia coli, a member of the Klebsiella-Enterobacter group, or oxidase positive. Samples of artificially seeded blood cultures (193 cultures) and patient blood cultures (78 cultures) were filtered into a Dynadepth test card with the Bac-T-Screen instrument (Vitek, Inc., Hazelwood, Mo.). Triton X-100 was then filtered into the test card to lyse the blood cells but not the entrapped bacteria, and either methylumbelliferone-labeled substrates or oxidase reagent was applied to the filter surface. The oxidase test was read within 30 s, and the methylumbelliferone and indole tests were read after a 10-min incubation at room temperature. Positive beta-galactosidase, beta-glucuronidase, and indole test results predicted the identification of E. coli with a 96 to 100% sensitivity and a 99 to 100% specificity. Positive beta-xylosidase and beta-galactosidase test results and negative oxidase and beta-glucuronidase test results were 85 to 93% sensitive and 100% specific for a Klebsiella-Enterobacter organism. A positive oxidase test result and negative beta-glucuronidase, beta-xylosidase, and indole test results were highly predictive of Pseudomonas aeruginosa (sensitivity, 100%; specificity, 99%). The procedures described are rapid and simple and provide a direct presumptive identification of the gram-negative rods most commonly found in blood cultures.
Bacteriological Techniques↗
Tissue-specific regulation of prolactin gene expression.
The past 2 years have seen dramatic progress in our understanding of the molecular basis of prolactin gene expression in the pituitary gland. The identification of the pituitary-specific factor Pit-1/GHF-1 has been a major advance, and it leads to new questions, such as the basis for the tissue-specificity of Pit-1/GHF-1 expression itself. It clearly cannot be the only factor involved, as it is found in three pituitary cell types, yet prolactin is expressed in only one of these. It is probable that a network of trans-acting factors, some tissue-specific and some ubiquitous but hormonally activated, interact to determine the overall pattern of expression of the prolactin gene, and the dissection of this system should provide some valuable insights into endocrine gene regulation in general.
Animals↗
Basic fibroblast growth factor affects DNA synthesis and cell function and activates multiple signalling pathways in rat thyroid FRTL-5 and pituitary GH3 cells.
We have used a recombinant human basic fibroblast growth factor (basic FGF) to study its effects on cell proliferation, gene expression and accumulation of cyclic AMP (cAMP) and inositol phosphates in two well-characterized endocrine cell lines, FRTL-5 rat thyroid and GH3 rat pituitary cells. Basic FGF induced a dose-dependent increase in mitogenesis (assessed by measuring incorporation of [3H]thymidine) in FRTL-5 cells (40 ng basic FGF/ml increased mitogenesis above the control value by 2148 +/- 108% (mean +/- S.E.M.), but inhibited mitogenesis in GH3 cells at all doses (85 +/- 4% of control with 40 ng basic FGF/ml]. Thyroglobulin mRNA concentration was increased in FRTL-5 cells (126 +/- 6% of control with 40 ng basic FGF/ml) as was prolactin mRNA in GH3 cells (246 +/- 11% of control with 40 ng basic FGF/ml), but GH mRNA in GH3 cells was not significantly affected by any dose of basic FGF. Intracellular cAMP was reduced by basic FGF in both FRTL-5 and GH3 cells (40 ng bFGF/ml giving 80 +/- 5% of the control value in FRTL-5, and 67 +/- 15% of the control value in GH3 cells) despite increased levels when FRTL-5 cells were stimulated with 150 microU TSH/ml (5645 +/- 484% of control) or GH3 cells were stimulated by 10 mumol forskolin/l (3347 +/- 396% of control). In both FRTL-5 and GH3 cells, accumulation of [3H]inositol phosphates were increased by 40 ng basic FGF/ml (201 +/- 6 and 330 +/- 51% of control values respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
An analysis of occupational risks for brain cancer.
We evaluated the risks of brain cancer in relation to employment history in a case-control study of 312 cases and 1,248 cancer controls. Subjects were identified through the Missouri Cancer Registry for the period 1984 through 1988. Job classification was based on data routinely abstracted from hospital records. Elevated risks were identified for certain white collar occupations: for men employed in engineering, the odds ratio (OR) = 2.1; 95% confidence interval (CI) = 0.4, 10.3; for social science professionals, the OR = 6.1; 95% CI = 1.5, 26.1. Among occupations with potential exposure to occupational carcinogens, increased risks were observed for men employed in agricultural crop production (OR = 1.5; 95% CI = 1.0, 2.4), printing and publishing (OR = 2.8; 95% CI = 1.0, 8.3), and brickmasons and tilesetters (OR = 2.5; 95% CI = 0.5, 11.5). Most of elevated brain cancer risks were due to astrocytic cancers, but the excess among agricultural workers occurred in other cell types. No increase in risk was noted for current cigarette smokers (OR = 0.9; 95% CI = 0.7, 1.5) or ex-smokers (OR = 1.0; 95% CI = 0.7, 1.5). This exploratory study indicates a need for further studies of occupational risks of brain cancer.
Astrocytoma↗
Mammography-guided stereotactic fine-needle aspiration cytology of nonpalpable breast lesions: prospective comparison with surgical biopsy results.
We assessed the usefulness of fine-needle aspiration cytology (FNAC) in evaluating nonpalpable breast abnormalities by prospectively performing stereotactic mammography-guided FNAC on 100 women undergoing surgical excisional biopsy. Mammographic and cytologic diagnoses, on a scale of 1 (benign) to 4 (malignant), were assigned for each case and compared with the surgical pathologic diagnosis. Sensitivity and specificity were examined at different diagnostic cutoff points for regarding a mammographic or cytologic diagnosis as positive or negative. Of the 100 breast biopsy specimens, 70 were benign and 30 were malignant. For both mammography and FNAC, the optimal diagnostic cutoff point was between diagnosis 2 (mammography, probably benign; cytology, atypical) and 3 (mammography and cytology both suspicious for malignancy). At this cutoff point, FNAC had a sensitivity of 0.77 and specificity of 1.00, vs 0.73 sensitivity and 0.79 specificity for mammography. Pearson coefficient analysis revealed significant correlations between both mammographic and FNAC diagnoses and surgical pathology (p less than .001 for both). Our results suggest that use of mammography-guided FNAC may reduce the number of breast biopsies performed for benign lesions.
Adult↗