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K Martin

Publications and source records attributed to K Martin.

At least 109 records · Page 6Linked to original sources
PubMed1998

Classification of breast cancer cells on the basis of a functional assay for estrogen receptor.

BACKGROUND: The receptor (ER) for estrogen (E2) is routinely assayed as a marker to determine the feasibility of anti-hormone therapy against breast cancer because ER-positive (ER+) tumors are much more likely to respond to anti-hormone therapy than are ER-negative (ER-). However 40% of ER+ breast cancer patients do not respond to anti-hormone therapy. We suggest that this unpredictability of therapeutic responses lies in the current ER assays, which measure only an initial component of the E2-responsive pathway, and that the difference depends upon altered downstream processes. We propose a functional criterion that subclassifies breast cancers on the basis of specific binding of ER to its cognate DNA sequence, the estrogen response element (ERE). MATERIALS AND METHODS: ER was identified in breast cancer cell lines by immunofluorescence assay, Western blot analysis, identification of ER-specific mRNA, and by interaction of the ER-ERE complex with three different ER-specific antibodies. ER-ERE complex formation was measured by electrophoretic mobility shift assay (EMSA). Transactivation of the E2-responsive gene was studied by transfection of cells with fusion gene construct with the promoter-containing ERE sequence and assay of reporter gene activity in the cell extracts. RESULTS: The growth of ER+ T47D cells was sensitive to tamoxifen, ICI-182,780, and ethynyl estradiol (EE2), whereas another ER+ breast cancer cell line, 21 PT, was resistant to these compounds. The estrogen receptor (ER) in the nuclear extracts of MCF-7 and T47D demonstrated hormone-dependent interaction with the response element (ERE) and also downstream transactivation of the E2-responsive PS2 promoter. But in the 21 PT cell line that was designated as ER- on the basis of ligand-binding assay and was found to be ER+ by all the other ER assays, ER-ERE interaction and PS2 promoter transactivation were independent of hormone. CONCLUSIONS: On the basis of the downstream functional assay of ER interaction with ERE, ER+ breast tumor cells can be subclassified into two categories. The first is E2-dependent (ERd+) and these cells should respond to anti-hormone therapy. The second type of ER interacts with ERE independent of E2 (ERi+) and constitutively transactivates responsive genes. It is predicted that the latter type of breast cancers will not respond to antihormone therapy.

Antibodies, Monoclonal↗
PubMed1997

Beta 1 integrin is essential for teratoma growth and angiogenesis.

Teratomas are benign tumors that form after ectopic injection of embryonic stem (ES) cells into mice and contain derivatives of all primitive germ layers. To study the role of beta 1 integrin during teratoma formation, we compared teratomas induced by normal and beta1-null ES cells. Injection of normal ES cells gave rise to large teratomas. In contrast, beta 1-null ES cells either did not grow or formed small teratomas with an average weight of <5% of that of normal teratomas. Histological analysis of beta 1-null teratomas revealed the presence of various differentiated cells, however, a much lower number of host-derived stromal cells than in normal teratomas. Fibronectin, collagen I, and nidogen were expressed but, in contrast to normal teratomas, diffusely deposited in beta1-null teratomas. Basement membranes were present but with irregular shape and detached from the cell surface. Normal teratomas had large blood vessels with a smooth inner surface, containing both host- and ES cell-derived endothelial cells. In contrast, beta 1-null teratomas had small vessels that were loosely embedded into the connective tissue. Furthermore, endothelial cells were always of host-derived origin and formed blood vessels with an irregular inner surface. Although beta 1- deficient endothelial cells were absent in teratomas, beta 1-null ES cells could differentiate in vitro into endothelial cells. The formation of a complex vasculature, however, was significantly delayed and of poor quality in beta1-null embryoid bodies. Moreover, while vascular endothelial growth factor induced proliferation of endothelial cells as well as an extensive branching of blood vessels in normal embryoid bodies, it had no effect in beta 1-null embryoid bodies.

Animals↗
PubMed1997

Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection.

Clinical isolates of primate immunodeficiency viruses, including human immunodeficiency virus type 1 (HIV-1), enter target cells by sequential binding to CD4 and the chemokine receptor CCR5, a member of the seven-transmembrane receptor family. HIV-1 variants which use additional chemokine receptors are present in the central nervous system or emerge during the course of infection. Simian immunodeficiency viruses (SIV) have been shown to use CCR5 as a coreceptor, but no other receptors for these viruses have been identified. Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages. The more efficient of these, gpr15, is also expressed in human CD4(+) T lymphocytes and activated rhesus macaque peripheral blood mononuclear cells. The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues. These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis.

Amino Acid Sequence↗
PubMed1997

E2F1-induced apoptosis requires DNA binding but not transactivation and is inhibited by the retinoblastoma protein through direct interaction.

E2F1 overexpression has been shown to induce apoptosis in cooperation with p53. Using Saos-2 cells, which are null for p53 and lack functional Rb, we have demonstrated that E2F1 overexpression can also induce apoptosis in the absence of p53 and retinoblastoma protein (Rb). E2F1-induced apoptosis can be specifically inhibited by Rb but not mdm2, which is known for its ability to inhibit p53-induced apoptosis. Through the study of the apoptotic function of a set of E2F1 mutants, it was clear that the transactivation and the apoptotic function of E2F1 are uncoupled. The transactivation-defective E2F1 mutants E2F1(1-374), E2F1(390-1)DF(delta mdm2), and E2F1(406-415)(delta Rb) can induce apoptosis as effectively as wild-type E2F1. In contrast to E2F1 transactivation, the DNA-binding activity of E2F1 was proven to be essential for its apoptotic function, as the DNA-binding-defective mutants E2F1(132) and E2F1(132)(1-374) failed to induce apoptosis. Therefore Rb may inhibit E2F1-induced apoptosis by mechanisms other than the suppression of the transactivation of E2F1. This hypothesis was supported by our observation that although Rb overexpression can specifically repress the apoptosis induced by wild-type E2F1 and a Rb-binding-competent E2F1 mutant E2F1(390-1)DF(delta mdm2), it failed to inhibit the apoptosis induced by mutants E2F1(1-374) and E2F1(delta 406-415)(delta Rb), which are defective or reduced in Rb binding and transactivation. All of these points argue for a novel function for E2F1 and Rb in controlling apoptosis. The results also indicate that transcriptional repression rather than the transactivation function of E2F1 may be involved in its apoptotic function. The results presented here may provide us some physiological implication of the repression function of the Rb-E2F1 complex.

Apoptosis↗
PubMed1997

Mechanistic analysis of RNA polymerase III regulation by the retinoblastoma protein.

The tumour suppressor protein RB restricts cellular growth. This may involve inhibiting the synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III. We have shown previously that RB can repress pol III transcription when overexpressed either in vitro or in vivo. We also demonstrated that pol III activity is elevated substantially in primary fibroblasts from RB-deficient mice. Here we address the molecular mechanism of this regulation. RB is shown to repress all types of pol III promoter. It can do this even if added after transcription complex assembly. Functional assays demonstrate that RB targets specifically the general pol III factor TFIIIB. A physical interaction between TFIIIB and RB is indicated by fractionation, pull-down and immunoprecipitation data. We show that TFIIIB activity is elevated in primary fibroblasts from RB-deficient mice. TFIIIB is a multisubunit complex that includes the TATA-binding protein (TBP) and a TFIIB-related factor called BRF. We show that RB itself contains regions of homology to both TBP and BRF and propose a model in which RB disrupts TFIIIB by mimicking these two components.

Amino Acid Sequence↗
PubMed1997

A thermal beam-shape phantom for ultrasound physiotherapy transducers.

Acoustic beam nonuniformities are not uncommon in physiotherapy ultrasound equipment and can lead to errors in delivered dose. A relatively simple thermal technique is described for mapping the intensity distribution in physiotherapy ultrasound beams that could be used for routine QA checks. The technique uses a thermochromic material sandwiched between layers that absorb ultrasound. The structure is used in a water bath to intersect the ultrasound beam. Thermal models predict that, with suitable absorbing materials and careful control of the surface temperature of the layers, sufficient spatial resolution and sensitivity can be achieved to show the intensity distribution in physiotherapy ultrasound beams. Thermal images of sections through physiotherapy ultrasound beams using this method correlate well with corresponding intensity maps generated by planar scanning with a hydrophone.

Hot Temperature↗
PubMed1997

Barrier precautions in trauma resuscitation: real-time analysis utilizing videotape review.

Blood-borne pathogens threaten all individuals involved in emergency health care. Despite recommendations by the Centers for Disease Control and the American College of Emergency Physicians, documented compliance with universal precautions in trauma resuscitation has been poor. The purpose of this study was to determine the factors that predispose to noncompliance with barrier precautions at a level I trauma center. Videotapes of trauma resuscitations performed during 1 month (n = 66) were reviewed. Full compliance with barrier precautions was documented in 89.1% of health care workers. Of the noncompliant health care workers, 50.7% were emergency department personnel and 47.8% were first responders to the trauma resuscitation area. Barrier precaution compliance improved from 62.5% to 91.8% with prenotification of patient arrival. Immediate access to barrier equipment is essential for all potential in-hospital first responders. Prehospital communication systems should be optimized to ensure prenotification.

Blood-Borne Pathogens↗
PubMed1997

Three-dimensional polyethylene wear of a press-fit titanium prosthesis. Factors influencing generation of polyethylene debris.

Between 1985 and 1990, 108 consecutive Harris-Galante I (Zimmer, Warsaw, IN) total hip arthroplasties were performed by four surgeons at a single hospital. At the time of follow-up evaluation, 80 hips were available for review. The mean rate of linear wear was 0.15 mm/y, mean rate of three-dimensional femoral head displacement was 0.21 mm/y, and mean rate of volumetric wear was 121 mm3/y. Eight hips (10%) in this series had radiologic osteolysis around either the femoral or acetabular component. A significantly greater volumetric wear rate was found in patients who were younger, those with a higher activity level, those who received a 32-mm-diameter femoral head, and those with vertical orientation of their acetabular component. No relationship could be made with patient weight, gender, Harris hip score, or cup diameter.

Adult↗
PubMed1997

Performance of a restrictive flow device and an electronic syringe driver for continuous subcutaneous infusion.

The aim of this study was to investigate the flow performance of the mechanical Springfusor 30 short model and the electronic Graseby MS16A. Flow rate was measured gravimetrically in a temperature-controlled cabinet. There was no statistically significant difference between the Graseby and Springfusor syringe drivers in the flow rate error at 25 degrees C. The percentage of flow rates within +/-20% accuracy during a 35-min periods at 25 degrees C was significantly less with the Graseby, being 91.9% compared with 100% for the Springfusor. Only 58.2% of flow rates with the Graseby were within the manufacturer claimed accuracy of +/-5%. The flow rate of the Springfusor was affected by temperature; at 30 degrees C the mean flow rate was 10.8% greater than at 25 degrees C. These results indicate that the Springfusor 30 had less flow rate variation than the Graseby MS16A. However, this would not be expected to cause noticeable clinical effects when used for opioid infusion in palliative care.

Electronics, Medical↗
PubMed1997

Bolus administration of eltanolone, thiopental, or etomidate does not affect systemic vascular resistance during cardiopulmonary bypass.

OBJECTIVE: To discover possible effects on systemic vascular resistance of the anesthetic induction agent eltanolone in comparison with thiopental and etomidate. The measurements were performed during cardiopulmonary bypass to maintain a constant cardiac output (approximately pump flow). DESIGN: The patients were prospectively randomized in three groups to receive either eltanolone, thiopental, or etomidate. SETTING: University hospital as a single center. PARTICIPANTS: Seventy-five patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: The anesthetic induction agents were repeated at the same dosage when cardiopulmonary bypass was instituted. The respective mean dosages were eltanolone, 0.41 +/- 0.1 mg/kg; thiopental, 2.88 +/- 0.62 mg/kg; etomidate, 0.26 +/- 0.06 mg/kg. MEASUREMENTS AND MAIN RESULTS: Systemic vascular resistance was calculated from the mean of a triple measurement (normal pump flow and +/- 20%). Points of measurement were before, and 2 and 5 minutes after injection of the hypnotic agent. None of the injected drugs made a significant change in the systemic vascular resistance. A small (not significant) decrease from 1,295 +/- 296 dyne/s/cm-5 to 1,196 +/- 323 dyne/s/cm-5 (mean +/- SD) was seen in the eltanolone group, whereas the other patients did not show any change during the study period. CONCLUSIONS: The reason for the significant reduction of the arterial pressure attributed to anesthetic induction by eltanolone may be more a cardiodepressive effect than a direct vasodilation.

Anesthetics, Intravenous↗
PubMed1997

Juvenile chronic arthritis: diagnosis and management of tibio-talar and sub-talar disease.

The aim of this study was to compare clinical evaluation of the site of hindfoot synovitis with contrast-enhanced magnetic resonance imaging (MRI) findings in children with juvenile chronic arthritis (JCA), and to evaluate the efficacy of selective guided intra-articular steroid injections. Thirteen symptomatic ankles of 11 consecutive JCA patients were examined clinically and with contrast-enhanced MRI. Pannus was demonstrated on MRI in both tibio-talar and sub-talar joints in 10 ankles, in the tibio-talar joint only in one ankle and in neither joint in two ankles. Correlation of clinical and MRI findings was good for the tibio-talar joint with concordance in 11/13 cases. Correlation was poor for the sub-talar joints. Of the 10 sub-talar joints shown to have pannus on MRI, only two were thought to have had definite clinical evidence of synovitis. Guided intra-articular steroid injection resulted in at least 6 months remission in 6/9 ankles compared with 1/10 ankles which had had previous unguided injections. We therefore recommend the use of image guidance for intra-articular triamcinolone hexacetonide injection in children with hindfoot synovitis.

Adolescent↗
PubMed1997

Severe juvenile dermatomyositis complicated by pancreatitis.

We report two boys with juvenile dermatomyositis (JDM) complicated by pancreatitis. One also had hepatitis and probably mild bowel vasculitis, while the other had catastrophic bowel vasculitis with multiple perforations. Both were on corticosteroids, but had features of active vasculitis. The former improved with high-dose i.v. pulsed methylprednisolone, while the latter improved only after immunosuppression with i.v. methylprednisolone, cyclophosphamide and plasmapheresis. Although bowel vasculitis is a known complication of severe JDM, pancreatitis and hepatitis are extremely rare. We have found in a literature search only three other reports of pancreatitis complicating JDM. We wish to alert physicians that pancreatitis may develop in JDM. It should be considered as a differential diagnosis in the child with active disease who develops abdominal pain. Control of vasculitis with adequate immunosuppression, as well as general supportive measures, may be valuable in the treatment of pancreatitis in JDM.

Adolescent↗
PubMed1997

Janibacter limosus gen. nov., sp. nov., a new actinomycete with meso-diaminopimelic acid in the cell wall.

New gram-positive bacteria were isolated from 1-year-old sludge from a wastewater treatment plant. The isolates are coccoid to rod-shaped, nonmotile aerobes that form neither spores nor mycelia. They are characterized by a peptidoglycan with directly cross-linked meso-diaminopimelic acid (type A1 gamma), by the presence of menaquinone MK-8(H4), and by the lack of mycolic acids. The strains have complex fatty acid patterns with i-C16:0 and straight-chain saturated and unsaturated fatty acids as major components. The G + C content of the DNA is 70 mol%. The results of chemotaxonomic studies and a 16S ribosomal DNA sequence comparison support our proposal to assign these bacteria to a new genus, the genus Janibacter gen. nov.; the type species is Janibacter limosus sp. nov., and the type strain of J. limosus is strain HKI 83 (= DSM 11140).

Actinomycetales↗
PubMed1997

Bogoriella caseilytica gen. nov., sp. nov., a new alkaliphilic actinomycete from a soda lake in Africa.

A new gram-positive, alkaliphilic, nonsporulating, rod-shaped bacterium is described. The organism was isolated from soda soil (Lake Bogoria, Kenya) and has the following characteristics. It is nonmotile, not acid fast, halotolerant, and microaerophilic, and optimal growth occurs at pH values between 9 and 10. The peptidoglycan type is of type A4 alpha, with lysine as the characteristic diamino acid and glutamic acid as a component of the interpeptide bridge. The major menaquinone is MK-8(H4). The polar lipids are phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, and an unknown phospholipid. 12-Methyltetradecanoic acid is the predominant fatty acid. The G + C content of the DNA is 70 mol%. The results of 16S ribosomal DNA sequence comparisons revealed that strain HKI 0088T represents a new lineage in the order Actinomycetales. Therefore, we concluded that strain HKI 0088T should be assigned to a new genus and species, for which we propose the name Bogoriella caseilytica gen. nov., sp. nov. The type strain and only strain of this genus and species is HKI 0088 (= DSM 11294).

Actinomycetaceae↗
PubMed1997

Demetria terragena gen. nov., sp. nov., a new genus of actinomycetes isolated from compost soil.

A novel actinomycete was isolated from compost soil and was studied taxonomically and phylogenetically. Cells of this organism were gram positive, not acid fast, nonmotile, nonsporulating, irregular coccoid to short rod shaped, and microaerophilic. The cell wall peptidoglycan contained lysine and was cross-linked via an L-Lys<--L-Ser<--D-Asp interpeptide bridge. The major menaquinone was MK-8(H4). The polar lipids were phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and two unknown phospholipids. Mycolic acids were absent. The cellular fatty acid profile was complex, with large amounts of saturated and monounsaturated straight-chain acids and smaller amounts of iso and anteiso branched-chain acids. The G+C content of the DNA was 66 mol%. Comparative 16S ribosomal DNA studies revealed that strain HKI 0089T represents a novel lineage within Actinobacteria (32) distinct from all previously described genera and most closely related to members of the genera Kytococcus, Dermacoccus, and Dermatophilus of the family Dermatophilaceae. On the basis of our results, we suggest that strain HKI 0089 should be classified in a new genus and species, for which we propose the name Demetria terragena. The type strain and the only strain of the genus and species is HKI 0089 (DSM 11295).

Actinomycetaceae↗
PubMed1997

Palliative care in a multicultural society: perceptions of health care professionals.

This study assesses the perceived competence of 191 Australian palliative care professionals in delivering crosscultural care. The relationship between the perceived competence levels of professionals and their experience and training is examined. Strategies to improve crosscultural palliative care, as suggested by palliative care providers, are also presented. Information about perceived competence and the kinds of difficulties encountered in crosscultural palliative care interactions form the basis of suggested guidelines for proposed education programmes. The results of this study suggest that specific education, rather than individual experience of crosscultural interactions, which may not always be positive, is needed to improve the competence of palliative care professionals. Education, therefore, is the key to the provision of culturally appropriate care to patients and their families from all cultural backgrounds.

Adult↗