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Biomedical subjects

S Green

Publications and source records attributed to S Green.

At least 325 records · Page 18Linked to original sources

Pneumatic retinopexy. A two-year follow-up study of the multicenter clinical trial comparing pneumatic retinopexy with scleral buckling.

The authors report 2-year follow-up information on 179 of 198 eyes (90%) enrolled in a previously published multicenter, randomized, controlled clinical trial comparing pneumatic retinopexy (PR) with scleral buckling (SB) for the management of selected retinal detachments. Scleral buckling was compared with PR with regard to redetachment after the initial 6-month follow-up period (1% versus 1%), overall attachment (98% versus 99%), subsequent cataract surgery (18% versus 4%; P less than 0.05), preoperative visual acuity (no significant difference), and final visual acuity of 20/50 or better in eyes with macular detachment for a period of 14 days or less (67% versus 89%; P less than or equal to 0.05). Reoperations after a failed PR attempt did not adversely affect visual outcome. After 2 years, PR continues to compare favorably with SB.

Cataract Extraction↗

Neutron and cobalt-60 gamma irradiation produce similar changes in DNA supercoiling.

The effects of 60Co gamma-ray and d(20 MeV)Be neutron irradiation on DNA supercoiling have been studied using a nucleoid rewinding technique. Irradiation of viable CHO AA8 cells on ice with from 4 to 25 Gy of either radiation produced a similar resistance to rewinding of nuclear supercoils after treatment with ethidium bromide. The restitution from the effects of 12 Gy of either radiation was also similar, leaving no detectable residual damage. The discrepancy between these data and the reduced ability of neutrons to produce DNA breaks, as defined by the alkaline elution assay, is explained by the discontinuous deposition of dose associated with neutron irradiation. It is suggested from a microdosimetric analysis that the neutron radiation interacts with DNA at sites on average 5-10 times further apart than the interactions with gamma rays. The long DNA sequences which results after neutron irradiation are consequently eluted inefficiently during alkaline elution, giving a reported RBE of approximately 0.3. Restrictions in the rewinding of individual supercoils are not dependent on the interionization distance and thus give rise to an RBE of approximately 1. Furthermore, the complete removal of DNA damage, as measured by this technique, supports the hypothesis that neutron toxicity is associated with incorrect, not incomplete, rejoining of the DNA molecule.

Animals↗

Modulation of oestrogen receptor activity by oestrogens and anti-oestrogens.

The oestrogen receptor is a member of a supergene family that includes receptors for steroid and thyroid hormones, vitamin D3, and retinoic acid. A number of additional members of the family have been cloned where the putative ligand remains to be identified. The oestrogen receptor is a ligand-activated transcription factor that modulates specific gene expression by binding to short DNA sequences (oestrogen response elements) located in the vicinity of oestrogen-regulated genes. Regions of the receptor responsible for hormone-binding. DNA-binding and activation of transcription, have been identified. The anti-oestrogen, tamoxifen (Nolvadex), behaves as a weak oestrogen agonist. A model, based upon our current understanding of the molecular mechanism of oestrogen action, will be presented to explain the cell and gene specific effects of some anti-oestrogens.

Amino Acid Sequence↗

Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators.

We have cloned a member of the steroid hormone receptor superfamily of ligand-activated transcription factors. The receptor homologue is activated by a diverse class of rodent hepatocarcinogens that causes proliferation of peroxisomes. Identification of a peroxisome proliferator-activated receptor should help elucidate the mechanism of the hypolipidaemic effect of these hepatocarcinogens and aid evaluation of their potential carcinogenic risk to man.

Amino Acid Sequence↗

A transcribed gene, containing a variable number of tandem repeats, codes for a human epithelial tumor antigen. cDNA cloning, expression of the transfected gene and over-expression in breast cancer tissue.

A monoclonal antibody, H23, that specifically recognizes a breast-tumor-associated antigen, was used to isolate a cDNA insert that codes for the antigenic epitope. Nucleotide sequencing of this cDNA, as well as a longer 850-bp cDNA insert, shows that they are composed of 60-bp (G + C)-rich tandem repeating units. The coding strand was determined and codes for a proline-rich 20-amino-acid repeat motif. A comparison of the highly conserved repeat unit with the deduced flanking amino acid sequences demonstrates conservation of specific subregions of the repeat consensus within the flanking amino acids. Hybridization of the 60-bp cDNA probe with RNAs extracted from a variety of primary and metastatic human tumors yields relatively high levels of hybrid with the breast carcinomas, as compared to lower hybrid levels with RNAs from other epithelial tumors. RNA extracted from breast tissue adjacent to the tumor or from benign breast tumors, demonstrates low or undetectable levels of hybridization. Probing Southern blots with the 60-bp repeat shows that the tumor antigen is highly polymorphic and contains a variable number of tandem repeats (VNTRs). The VNTR nature of the gene was confirmed by probing Southern blots with unique genomic sequences that are physically linked to an isolated gene fragment that also contains the tandem repeat array. Mouse cells transfected with this gene fragment produce tumor antigen that is readily detected by H23 monoclonal antibodies. The allelic forms seen in 10 different primary human tumors demonstrate 100% concordance with the various mRNA species expressed. These studies are extended to the protein forms detected by immunoblot analyses that show both a correlation of the expressed tumor antigen species with the allelic forms as well as significantly increased expression in breast cancer tissue. The above studies unequivocally establish the over-expression of a VNTR gene coding for an epithelial tumor antigen in human breast cancer tissue.

Amino Acid Sequence↗

Expression of calmodulin gene is down-regulated in diabetic BB rats.

In past studies, we have demonstrated that in streptozotocin-induced diabetic or spontaneously diabetic (BB) animal models, low Km cAMP phosphodiesterase and calmodulin are decreased while a low MW inhibitor of calmodulin is increased. To extend these studies, we have determined the rate of [35S]-methionine incorporation into calmodulin in isolated fat cells from these diabetic animals, i.e. streptozotocin-induced diabetic and the BB rats, spontaneous diabetic rat, non-diabetic rat, and control. We found markedly decreased rates of synthesis of calmodulin in the fully diabetic BB rat. In order to investigate the mechanism of the reduced calmodulin biosynthesis, we probed poly A+ mRNA from control and diabetic rat livers with a calmodulin specific anti-sense oligonucleotide probe and found that the fully diabetic animals, streptozotocin-induced diabetic and genetically diabetic BB, contained markedly reduced levels of calmodulin transcripts. Thus, both calmodulin protein and its putative mRNA are decreased in diabetic rat liver. We believe that in uncontrolled diabetes, the observed elevation in the levels of cyclic AMP in plasma and tissue results in part from decreased activity of phosphodiesterase. The insulin-sensitive phosphodiesterase appears to be regulated by calmodulin. We hypothesize that cyclic AMP phosphodiesterase inactivation in diabetes results in part from insulin insufficiency and to a less well-defined genetic lesion leading to calmodulin down-regulation.

Actins↗

Sustained performance and some effects on the design and operation of complex systems.

Man, increasingly the limiting element in the military man-machine system, must often operate for several days in a high-risk environment with little or no sleep. It is necessary, therefore, to have some knowledge of the likely effects of sleep deprivation to predict his behaviour and minimize the adverse effects of sleep loss. The early work of the Army Personnel Research Establishment (APRE) concentrated on studying the infantryman in field trials, characterized by more realism and of greater length than previously attempted. Although measures of cognitive functioning were included in these trials, continuous cognitive performance was not assessed, nor was performance on complex tasks. An opportunity to remedy this situation arose because of a newer study concerned with controlling a removely-piloted air vehicle from a ground control station (GCS). A 65-hour experiment was designed during which subjects performed continuously either on the GCS simulator or on a battery of cognitive tests, mood scales, and physiological assessments. Results showed that whereas performance showed the usual deterioration in the test battery, it held up remarkably well on the simulator. Several reasons for this difference are suggested.

Equipment Design↗

Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin.

Cytokines such as tumor necrosis factor alpha (TNF) profoundly affect endothelial cell function, promoting for example interaction with leukocytes and inducing a procoagulant phenotype. Changes of this nature are likely to be central to the proinflammatory effects of TNF. In order to elucidate molecular mechanisms by which TNF alters endothelial cell function we utilized differential plaque hybridization to identify TNF-responsive genes. Forty TNF-inducible cDNAs were identified which on cross-hybridization were found to arise from six unique genes. DNA sequencing of these cDNAs revealed two encoded known cytokine-induced genes, endothelial leukocyte adhesion molecule 1 and neutrophil chemotactic factor. One of the cDNAs encodes a recently described monocyte-specific chemotactic factor not previously associated with endothelium. The production of a monocyte chemotaxin by cytokine-activated endothelium has important implications for understanding the role of the vessel wall in disease states such as atherosclerosis and may also in part explain the indirect angiogenic activity of TNF. The three other cDNAs are completely novel as judged by data bank searches of partial DNA sequences and remain unidentified. On exposure of endothelial cells to TNF there is a rapid and substantial increase in levels of mRNA encoding the six genes, which are further superinduced by cycloheximide. Thus these represent primary response genes as their induction does not depend on protein synthesis. Interleukin-1 beta and lipopolysaccharide are also potent inducers. Nuclear run-on studies revealed that in most cases induction by TNF is mediated largely at the transcriptional level.

Biological Factors↗

Growth factor binding and bioactivity in human kidney epithelial cell cultures.

Insulinlike growth factors (IGF) and epidermal growth factor (EGF) are produced in renal tissue, as are specific receptors for these hormones. To evaluate the significance of these observations to regulation of renal tubular cell proliferation, we have examined the interaction of IGF and EGF with cultured human proximal tubular epithelial cells (HPT). HPT cells showed specific binding of IGF-1, insulin, and EGF. IGF-1 binding was inhibited by antibody to the type 1 IGF receptor (alpha-IR3). Insulin receptors and type 1 IGF receptors were identified by bifunctional cross-linking. IGF-1, insulin, and EGF stimulated [3H]thymidine incorporation by 77, 73, and 87%, respectively. Half maximal stimulation by IGF-1, insulin, and EGF were produced with 4 X 10(-9) M, 2.5 X 10(-8) M, and 8 X 10(-10) M concentrations of these hormones. Alpha-IR3 inhibited stimulation of thymidine incorporation by IGF-1 and insulin but had no effect in EGF-stimulated thymidine incorporation. EGF and high concentrations of insulin both stimulated cell proliferation by 83 and 79%, respectively. These data are consistent with regulation of tubular epithelial proliferation by IGF-1, insulin, and EGF and suggest that the mitogenic activity of both insulin and IGF-1 is mediated by the type 1 IGF receptor.

Cells, Cultured↗

A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study.

Forty-one eligible patients with metastatic or recurrent carcinoma of the uterine cervix received 149 courses of carboplatin. The drug was administered at a starting dosage of 400 mg/m2 IV every 28 days. The overall response rate was 15% (two complete responses, four partial responses; 95% confidence interval 6-29%) and response durations were 2.0, 2.0, 2.5 +, 2.5+, 5.25 +, and 6.75 months. The major toxic effects included nausea and vomiting in 48% of courses, anemia in 47%, leukopenia in 38%, and thrombocytopenia in 22%. The activity of carboplatin against advanced cervical cancer is modest and similar to the activity of cisplatin alone. However, the toxicity profile of carboplatin is substantially better than that of cisplatin and warrants exploration of this agent against cervix cancer in more aggressive regimens or in combination with other agents.

Carboplatin↗

A phase II trial of cisplatin and 5-fluorouracil with allopurinol for recurrent or metastatic carcinoma of the uterine cervix: a Southwest Oncology Group trial.

On the strength of recent evidence of the activity of the combination of cisplatin and 5-fluorouracil against squamous malignancies of the esophagus and head and neck, this regimen was evaluated in a phase II trial against metastatic or recurrent squamous carcinoma of the uterine cervix. Cisplatin was administered at a dosage of 100 mg/m2 iv bolus and 5-fluorouracil was continuously infused iv at a dosage of 1000 mg/m2/day for 4 days. In an effort to determine whether the toxicities of 5-fluorouracil could be ameliorated by coadministration of allopurinol, patients were randomized to receive allopurinol, 900 mg orally, an odd or even courses of therapy beginning 5 days before 5-fluorouracil administration and continuing until conclusion of the infusion. Fifty-two eligible patients received 177 evaluable courses of treatment. The overall response rate was 28% (8 complete responses and 6 partial responses). Toxicity was confined to nausea and vomiting (81% of courses), anemia (47%), leukopenia (37%), oral mucositis (15%), diarrhea (6%), and thrombocytopenia (4%). Allopurinol produced no improvement in treatment-related toxicities. Allopurinol did not permit substantial increases in 5-fluorouracil dosage.

Adult↗

Serious conduct problems in the children of adolescent mothers: disentangling confounded correlations.

Early motherhood (less than 20 years of age) was found to be significantly correlated (r = .33) with the number of DSM-III symptoms of conduct disorder in a sample of 253 boys aged 6-13 years who had been referred to outpatient clinics. The following models were compared using path analysis: (a) Teenage motherhood, parental antisocial personality, and SES each contribute uniquely to the prediction of childhood conduct problems; (b) teenage motherhood mediates the association of SES and parental antisocial personality with child conduct problems; and (c) teenage motherhood is spuriously related with child conduct problems because of common associations with SES and parental antisocial personality. Model (c) best fit our data. Similar results were obtained whether maternal age at the birth of the firstborn child or the proband child was used to define maternal age and when teenage motherhood was defined as giving birth at less than 18 years.

Adolescent↗

Phase II study of fludarabine phosphate (NSC 312887) in patients with advanced cervical cancer. A Southwest Oncology Group study.

Twenty evaluable patients with advanced cervical cancer refractory to one prior chemotherapy regimen were treated with a 5-day schedule of fludarabine phosphate. No responses were noted. The major toxicities were anemia and leukopenia. Based on this study, fludarabine phosphate does not appear to be an active agent for patients with chemotherapy refractory cervical cancer.

Adult↗

Effectiveness of the kinetic treatment table for preventing and treating pulmonary complications in severely head-injured patients.

The efficacy of using the Kinetic Treatment Table (KTT) to prevent or reduce pulmonary complications in severely head-injured patients is unclear. This study is a prospective, randomized trial using the KTT vs. conventional bed care in severely head-injured patients. Outcome measures were hospital length of stay (LOS), mortality, CNS morbidity at hospital discharge, and rate of improvement of pulmonary status as gauged by chest radiograph, arterial/alveolar PO2 ratio, patient temperature, WBC count, suctioning frequency, sputum volume, and days on ventilator. The KTT group (n = 23) and conventional bed care group (n = 26) were well matched for age, sex, severity of injury, and pulmonary status. There was no significant difference in mortality, CNS morbidity, LOS in ICU or hospital, or rate of pulmonary improvement between the groups. The efficacy of the KTT in reducing pulmonary complications in head-injured patients remains unclear.

Acute Disease↗

Comparison of DSM-III and DSM-III-R diagnoses for prepubertal children: changes in prevalence and validity.

A structured and reliable diagnostic procedure based on a revised version of the Diagnostic Interview Schedule for Children for children, parents, and teachers was used to assign both DSM-III and DSM-III-R diagnoses to 177 outpatient boys aged 7 to 12 years. Compared to their DSM-III counterparts, DSM-III-R oppositional defiant disorder was 25.5% less prevalent, DSM-III-R dysthymia was 37.8% less prevalent, and DSM-III-R conduct disorder (CD) was 44.3% less prevalent. However, DSM-III-R attention deficit hyperactivity disorder was 14.4% more prevalent than DSM-III attention deficit disorder with hyperactivity. The two definitions of CD were compared to exemplify an empirical approach to diagnostic validation. The DSM-III-R diagnosis of CD appears to be more valid as it is more strongly associated with police contacts, school suspensions, and history of antisocial personality disorder in the biological father, but both CD diagnoses are associated with family histories of criminal convictions.

Child↗

The complication of pneumatic retinopexy.

There have been 26 published series with a total of 1274 detachments operated with pneumatic retinopexy. Eighty percent were reattached with a single procedure and 98% with reoperations. New breaks occurred in 13% and PVR in 4%. The complications published in 101 papers on pneumatic retinopexy in the last 5 years are analyzed as to frequency, prevention, management, and results.

Cryosurgery↗