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Biomedical subjects

S Garrett

Publications and source records attributed to S Garrett.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effects of 60-Hz fields, estradiol and xenoestrogens on human breast cancer cells.

If exposure to xenoestrogens or electromagnetic fields (EMFs) such as 60 Hz contributes to the etiology of breast cancer, it is likely that they must stimulate the growth of breast cells, damage genetic material or enhance the effects of other mitogenic or mutagenic agents (co-promotion). Therefore, the ability of xenoestrogens or exposure to 60-Hz fields to stimulate the entry of growth-arrested human breast cancer cells into the cell cycle was determined using cyclin-dependent kinase 2 (Cdk2) activity, synthesis of cyclin D1 and cdc2 activity. Exposure of estrogen receptor-positive MCF-7 or T-47D cells to estrogen and xenoestrogens (DDT and Red No. 3) increased Cdk2 and cyclin B1-cdc2 activity and cyclin D1 synthesis. Exposure of breast cancer cells to 12 mG or 1 or 9 G electromagnetic fields at 60 Hz failed to stimulate Cdk2 or cyclin B1-cdc2 activity or cyclin D1 synthesis. Simultaneous co-exposure of cells to 60-Hz fields and chemical promoters did not enhance Cdk2 activation above the levels produced by the chemical promoter alone. Estrogen and xenoestrogens also stimulated binding of the estrogen receptor to the estrogen receptor element but the EMF did not. Phorbol 12-myristate 13-acetate (PMA) induced phosphorylation of p53 and pRb1O5 in MCF-7 cells, but EMF exposure had no effect. DNA-damaging chemotherapeutic agents and Red Dye No. 3 were found to increase p53 site-specific DNA binding in breast cancer cells, but EMF exposure did not. Differential display analysis failed to detect any effect of EMF exposure on gene expression in MCF-7 cells, whereas the effects of estradiol were detected. These studies suggest that estrogen and xenoestrogens stimulate growth-arrested breast cancer cells to enter the growth cycle, but EMF exposure does not. Site-specific p53-DNA binding was increased in MC F-7 cells treated with DNA-damaging agents, but not by EMF exposure. EMF exposure does not appear to act as a promoter or DNA-damaging agent for human breast cancer cells in vitro.

Base Sequence↗
PubMed1995

SOK2 may regulate cyclic AMP-dependent protein kinase-stimulated growth and pseudohyphal development by repressing transcription.

Yeast cyclic AMP (cAMP)-dependent protein kinase (PKA) activity is essential for growth and cell cycle progression. Dependence on PKA function can be partially relieved by overexpression of a gene, SOK2, whose product has significant homology with several fungal transcription factors (StuA from Aspergillus nidulans and Phd1 from Saccharomyces cerevisiae) that are associated with cellular differentiation and development. Deletion of SOK2 is not lethal but exacerbates the growth defect of strains compromised for PKA activity. Alterations in Sok2 protein production also affect the expression of genes involved in several other PKA-regulated processes, including glycogen accumulation (GAC1) and heat shock resistance (SSA3). These results suggest SOK2 plays a general regulatory role in the PKA signal transduction pathway. Expression of the PKA catalytic subunit genes is unaltered by deletion or overexpression of SOK2. Because homozygous sok2/sok2 diploid strains form pseudohyphae at an accelerated rate, the Sok2 protein may inhibit the switch from unicellular to filamentous growth, a process that is dependent on cAMP. Thus, the product of SOK2 may act downstream of PKA to regulate the expression of genes important in growth and development.

Amino Acid Sequence↗
PubMed1995

Guided tissue regeneration in human furcation defects after using a biodegradable barrier: a multi-center feasibility study.

This multi-center study evaluated guided tissue regeneration (GTR) in Class II furcation defects using a polylactic acid biodegradable barrier in 29 patients with mandibular and maxillary molar defects. Following an initial hygienic phase, surgical flaps were elevated, and the sites scaled and root planed. Furcation defect perimeter was measured and a customized barrier (thickness 600 to 750 mu) was applied to cover the defect. Barriers adhered directly to tooth and bone. At baseline, sites were measured for probing depth (PD) (6.0 +/- 0.2 [SE] mm), gingival margin location (GML) (-0.2 +/- 0.2 mm), and attachment level in both vertical (AL-V) (6.2 +/- 0.2 mm) and horizontal (AL-H) (5.4 +/- 0.2 mm) directions. After the surgical procedure, there was good compatibility between the gingival tissues and barrier material. Clinically, barriers fragmented and became displaced in 3 to 6 weeks. Substantial granulation tissue was sometimes present between barrier and root surfaces. Comprehensive periodontal examination parameters were measured 3, 4, 6, 9, and 12 months after baseline. A repeated measures ANOVA was used to evaluate changes from baseline. At 6 and 12 months postsurgery, GML was close to the presurgical level (-0.5 +/- 0.2 mm). There was clinically and statistically significant improvement in all other parameters: mean PD reduction (2.2 mm), AL-V gain (1.7 mm), and AL-H gain (2.5 mm). These results indicated favorable clinical regenerative outcomes after using this barrier material in Class II furcation defects in humans.

Adult↗
PubMed1995

Diarrhoeal diseases in the White Mountain Apaches: clinical studies.

Acute diarrhoeal diseases continue to be a major health problem in certain underprivileged populations in the United States, including native Americans living in reservations. To describe the features of patients with diarrhoeal diseases requiring medical care, those attending the medical facilities of the Fort Apache Indian Reservation, Whiteriver, Arizona, were studied during 1981-1985. Clinical and aetiological information was obtained on 535 patients which constitute a 20% sample of those attending the outpatient clinic and all 386 patients who required 550 hospitalizations. Rotavirus, enterotoxigenic Escherichia coli, and Shigella were the most common aetiologic agents, a pattern similar to that seen in the developing countries. The clinical features of diarrhoeal illness and the frequent associated occurrence of acute respiratory symptoms, however, were remarkably similar, regardless of aetiology.

Acute Disease↗
PubMed1995

Diarrhoeal diseases in the White Mountain Apaches: epidemiologic studies.

Acute diarrhoeal disease in children is known to be a major public health problem among native Americans living in reservations in the southwestern part of the United States. This study was undertaken to describe the epidemiology and causative agents of diarrhoea more completely, with the expectation that this information may help in the ultimate control of the disease in this population. Three interrelated epidemiologic studies were carried out in the White Mountain Apache Tribe, Whiteriver, Arizona, during 1981-1985: a three-year longitudinal study on a cohort of 112 newborns, a longitudinal two-year study in a cohort of 200 families, and a case-control study on 1,072 children with diarrhoea attending a medical facility. Both epidemiologic and microbiological patterns of diarrhoeal disease were found to be very similar to those seen in developing countries, indicating the need for basic improvements in sanitation and hygiene in this population.

Acute Disease↗
PubMed1994

SMS1, a high-copy suppressor of the yeast mas6 mutant, encodes an essential inner membrane protein required for mitochondrial protein import.

MAS6 encodes an essential inner membrane protein required for mitochondrial protein import in the yeast Saccharomyces cerevisiae (Emtage and Jensen, 1993). To identify new inner membrane import components, we isolated a high-copy suppressor (SMS1) of the mas6-1 mutant. SMS1 encodes a 16.5-kDa protein that contains several potential membrane-spanning domains. The Sms1 protein is homologous to the carboxyl-terminal domain of the Mas6 protein. Like Mas6p, Sms1p is located in the mitochondrial inner membrane and is an essential protein. Depletion of Sms1p from cells causes defects in the import of several mitochondrial precursor proteins, suggesting that Sms1p is a new inner membrane import component. Our observations raise the possibility that Sms1p and Mas6p act together to translocate proteins across the inner membrane.

Amino Acid Sequence↗
PubMed1994

The Yak1 protein kinase of Saccharomyces cerevisiae moderates thermotolerance and inhibits growth by an Sch9 protein kinase-independent mechanism.

The growth defect associated with the loss of yeast A kinase activity can be alleviated by the overexpression or deletion of two other kinases, Sch9 and Yak1, respectively. Using tests of epistasis, we have shown that Sch9 and Yak1 define separate signaling pathways and must, therefore, suppress the A kinase defect by different mechanisms. Nevertheless, the Yak1 kinase appears to regulate cellular processes that are under A kinase control. For example, acquisition of heat resistance is correlated with Yak1 kinase activity, such that YAK1-overexpressing cells are over 200-fold more resistant than isogenic yak1 strains. These results, for the first time, associate a phenotype, other than suppression of the A kinase growth defect, with the loss of Yak1 activity and argue a broader role for the Yak1 kinase in cell growth.

Cell Cycle↗
PubMed1994

Suppression of a yeast cyclic AMP-dependent protein kinase defect by overexpression of SOK1, a yeast gene exhibiting sequence similarity to a developmentally regulated mouse gene.

Saccharomyces cerevisiae cyclic AMP-dependent protein kinase (A kinase) activity is essential for growth and cell cycle progression. Dependence on A kinase function can be partially relieved by the inactivation of a second kinase encoded by the gene YAK1. We have isolated two new genes, SOK1 and SOK2 (suppressor of kinase), as gene dosage suppressors of the conditional growth defect of several temperature-sensitive A kinase mutants. Overexpression of SOK1, like lesions in YAK1, also restores growth to a strain (tpk1 tpk2 tpk3) lacking all A kinase activity. The SOK1 gene is not essential, but a sok1::HIS3 disruption abrogates suppression of an A kinase defect by yak1. These results suggest that Yak1 and Sok1 define a linear pathway that is partially redundant with that of the A kinase. Activation of Sok1, by SOK1 overexpression or by inactivation of the negative regulator Yak1, renders a cell independent of A kinase function. The implications of such a model are particularly intriguing in light of the nuclear localization pattern of the overexpressed Sok1 protein and the primary sequence homology between SOK1 and a recently described, developmentally regulated mouse gene.

Amino Acid Sequence↗
PubMed1994

Zinc protoporphyrin and iron-deficient erythropoiesis.

Iron-deficient erythropoiesis may occur in patients with adequate levels of storage iron as well as those with tissue iron deficiency. Here we compare two methods of detecting iron-deficient erythropoiesis. The measurement of percent hypochromic cells in the full blood count provides a direct indicator of iron-deficient erythropoiesis. The zinc protoporphyrin (ZPP) determination is simple, precise and reproducible, and also appears to provide a sensitive index of iron-deficient erythropoiesis. There was a significant correlation between ZPP levels and percent hypochromic cells in patients with iron deficiency anaemia, rheumatoid arthritis and with patients with renal failure undergoing dialysis and receiving erythropoietin. However in the latter group ZPP levels were raised in almost all patients, suggesting that there may be interference by other metabolites in the assay. This may be overcome by washing the red cells before assay, but the procedure becomes cumbersome. If the laboratory is equipped to determine percent hypochromic cells during the blood count this direct measure of iron-deficient erythropoiesis dispenses with the need to determine ZPP. Otherwise ZPP determinations on washed cells may be of diagnostic use.

Anemia, Hypochromic↗
PubMed1994

Treatment of mandibular class III periodontal furcation defects. Coronally positioned flaps with and without expanded polytetrafluoroethylene membranes.

Twenty-six mandibular class III furcation defects were treated in 26 subjects using a regenerative therapy that included citric acid root conditioning, placement of freeze-dried decalcified bone allograft and coronally positioned flaps secured by crown-attached sutures. In addition to this therapy, expanded polytetrafluoroethylene (ePTFE) membranes were placed in 14 of the 26 defects. The effect of these therapies was evaluated after 52 to 60 weeks through a series of soft and hard tissue probing measurements including residual furcation classification. For both treatments, mean improvements were observed for furcal probing attachment levels, furcal bone levels, and defect volumes. However, only a few of these through-and-through defects had become closed as judged by a panel of 3 independent examiners. Four defects in each of the 2 treatment groups had changed from Class III to Class I/II or Class II/II evaluated with the soft tissue in place. One defect treated without membrane and 3 defects treated with membranes had changed from Class III to Class II as recorded after reflection of the soft tissues at re-entry. Little difference was observed between defects treated with and without membranes. Further studies with larger sample sizes and longer observation times are needed to fully evaluate these regenerative procedures and their potential for healing Class III furcation defects.

Adult↗
PubMed1994

A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index.

OBJECTIVE: After pain and stiffness, one of the most important complaints of patients with ankylosing spondylitis (AS) is disability. The main aims of treatment are to control pain but also to improve function. Various methods of assessing function exist but are either not specific for the disease or have not been adequately validated. As a result of this deficiency we developed the Bath Ankylosing Spondylitis Functional Index (BASFI) as a new approach to defining and monitoring functional ability in patients with AS. METHODS: This self-assessment instrument was designed by a team of medical professionals in conjunction with patients, and consists of 8 specific questions regarding function in AS and 2 questions reflecting the patient's ability to cope with everyday life. Each question is answered on a 10 cm horizontal visual analog scale, the mean of which gives the BASFI score (0-10). The questionnaire was completed 257 times in total: once by 116 outpatients and by 47 inpatients on 3 occasions over a 3-week intensive physiotherapy course. In addition, the instrument was compared with the Dougados functional index. RESULTS: Patients scores covered 95% of the BASFI range, giving a normal distribution of results. In contrast only 65% of the Dougados functional index scale was used. Furthermore, over the 3 week period of inpatient treatment, the BASFI revealed a significant improvement in function (20%, p = 0.004) while there was a less impressive change in the Dougados functional index (6%, p = 0.03). This demonstrates the superior sensitivity of the BASFI: Consistency was good for both indices (p < 0.001), as was the relationship between patient perception of function and function as assessed by an external observer (p < 0.001). CONCLUSION: The BASFI satisfies the criteria required of a functional index: it is quick and easy to complete, is reliable and is sensitive to change across the whole spectrum of disease.

Activities of Daily Living↗
PubMed1994

A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index.

OBJECTIVE: Disease status, in terms of disease activity, disease progression and prognosis is difficult to define in ankylosing spondylitis (AS). No gold standard exists. Therefore, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a self-administered instrument, has been developed as a new approach to defining disease activity in patients with AS. METHODS: The index, designed by a multidisciplinary team with input from patients, consists of six 10 cm horizontal visual analog scales to measure severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness (both qualitative and quantitative). The final BASDAI score has a range of 0 to 10. The index was distributed to a cross section of patients, including inpatients receiving 3 weeks of intensive physiotherapy treatment and hospital outpatients. BASDAI was completed by a total of 154 patients. Validation of the new instrument was achieved through analysis of user friendliness, reliability (consistency), score distribution and sensitivity to change. Comparisons were made with a previous Bath disease activity index (DAI) and the Newcastle Enthesis Index. RESULTS: The BASDAI was found by patients to be quick and simple to complete (mean: 67 s). Test-retest reliability was good (r = 0.93; p < 0.001), as was the distribution of scores across the scale (score range: 0.5-10; mean: 4.31). BASDAI was sensitive to change, reflecting a 16% (mean) improvement in inpatient scores after 3 weeks of treatment. It is superior to the DAI in terms of construct and content validity and to the Enthesis Index in all aspects. CONCLUSION: In summary, BASDAI is user friendly, reliability, sensitive to change and reflects the entire spectrum of disease. It is a comprehensive self-administered instrument for assessing disease activity in AS.

Data Interpretation, Statistical↗
PubMed1994

Periodontal regeneration with bone grafts.

This paper reviews the clinical and histologic results following the use of bone autografts and allografts in periodontal therapy. Results from case reports and controlled clinical trials are discussed. Reports about bone grafts and combination procedures, including coronally positioned flaps and guided tissue regeneration procedures, are also reviewed. Studies analyzing long-term stability of grafts are discussed, as well as tissue banking procedures and safety considerations when freeze-dried bone allografts are used. Tables summarizing the results and methodologies of clinical trials cited are included to provide a method of comparison between the studies. The analysis of results of clinical trials using bone graft materials indicates that there is a consistent pattern of more bone fill in grafted versus nongrafted sites. However, the magnitude of this fill represents only about 60% of the treated defects.

Alveolar Bone Loss↗
PubMed1993

Ceramide-mediated growth inhibition and CAPP are conserved in Saccharomyces cerevisiae.

Ceramide is emerging as a potential physiologic regulator of growth and differentiation in mammalian cells. This regulation may be mediated through the action of a serine/threonine ceramide-activated protein phosphatase (CAPP). In this study, the existence of a ceramide-mediated pathway of cell regulation in Saccharomyces cerevisiae was investigated. Incubating exponentially growing S. cerevisiae cells with 1-20 microM cell-permeable ceramide (C2-ceramide) produced a dose-dependent inhibition of proliferation. A number of other lipids and detergents, such as arachidonate, oleate, Triton X-100, dioctanoylglycerol, and phenylaminoalcohol ceramide analogs, were largely ineffective, demonstrating the specificity of the response. Stereospecificity was demonstrated, in that the D enantiomer of erythro-C2-ceramide was more potent than the L enantiomer. More dramatically, a highly specific structural requirement for C2-ceramide was demonstrated, in that 1-12 microM C2-dihydroceramide was completely ineffective at inhibiting growth. Since C2-dihydroceramide lacks the 4-5 trans double bond present in C2-ceramide, this suggests that the antiproliferative properties of C2-ceramide depend upon the presence of the double bond. This raises an interesting possibility; the dehydrogenase responsible for introduction of the double bond during endogenous ceramide synthesis may regulate cell growth by controlling the cellular concentrations of dihydroceramide and ceramide. The oxygenase responsible for introduction of the final hydroxyl group in phytoceramide could provide a similar regulatory function in yeast. The potential role of CAPP in ceramide action in yeast was investigated next. Crude extracts of S. cerevisiae also contained a ceramide-dependent serine/threonine phosphatase activity, which was sensitive to inhibition by okadaic acid. This enzyme exhibited stereospecificity and structural requirements identical to that of the ceramide-induced growth inhibition. We conclude that both the growth-inhibitory response to ceramide and CAPP activity are conserved in S. cerevisiae. The identical stereochemical and structural requirements in both the biological and phosphatase assays suggest that the anti-proliferative effects of ceramide in yeast may be mediated in part through the action of CAPP.

Ceramides↗
PubMed1993

Treatment of periodontal furcation defects. Coronally positioned flap with or without citric acid root conditioning in class II defects.

A total of 27 mandibular, buccal class II furcation defects were treated in 16 subjects using a coronally positioned flap procedure, with or without citric acid conditioning of the root surfaces. The effect of the therapies was evaluated from a series of soft and hard tissue measurements. Mean improvements were slightly greater for acid treated than for non-acid treated defects. However, none of the mean differences reached statistical significance, indicating that citric acid conditioning may not be a necessary part of the regenerative, coronally positioned flap procedure in mandibular furcations.

Acid Etching, Dental↗
PubMed1993

Casein kinase I-like protein kinases encoded by YCK1 and YCK2 are required for yeast morphogenesis.

Casein kinase I is an acidotropic protein kinase class that is widely distributed among eukaryotic cell types. In the yeast Saccharomyces cerevisiae, the casein kinase I isoform encoded by the gene pair YCK1 and YCK2 is a 60- to 62-kDa membrane-associated form. The Yck proteins perform functions essential for growth and division; either alone supports growth, but loss of function of both is lethal. We report here that casein kinase I-like activity is associated with a soluble Yck2-beta-galactosidase fusion protein in vitro and that thermolabile protein kinase activity is exhibited by a protein encoded by fusion of a temperature-sensitive yck2 allele with lacZ. Cells carrying the yck2-2ts allele arrest at restrictive temperature with multiple, elongated buds containing multiple nuclei. This phenotype suggests that the essential functions of the Yck proteins include roles in bud morphogenesis, possibly in control of cell growth polarity, and in cytokinesis or cell separation. Further, a genetic relationship between the yck2ts allele and deletion of CDC55 indicates that the function of Yck phosphorylation may be related to that of protein phosphatase 2A activity.

Alleles↗