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Biomedical subjects

S Gray

Publications and source records attributed to S Gray.

At least 55 records · Page 3Linked to original sources
PubMed2000

The physico-chemical properties of salmeterol and fluticasone propionate in different solvent environments.

The physico-chemical properties of two anti-asthmatic drugs, salmeterol xinafoate and fluticasone propionate, have been studied in both aqueous and non-aqueous solvent environments. Ultraviolet-visible (UV-Vis) spectroscopy, fluorescence spectroscopy and electrospray ionisation mass spectrometry (ESI-MS) have been used to characterise the interaction of the drugs in 70:30 (v/v) methanol/water solutions. First derivative UV-Vis spectra measurements indicate that an interaction takes place between the two drugs in a binary solvent system. Fluorescence studies indicate that an increase in the concentration of fluticasone propionate results in a decrease in the fluorescence signal of the salmeterol for mixed solutions of the drugs. Analysis of a mixture of the two drug solutions using mass spectrometry also shows evidence of salmeterol-fluticasone propionate interaction and dimer formation with respect to both the salmeterol and the fluticasone propionate. Model metered dose inhalers (MDI) of both individual samples and mixtures of the drugs were formulated as suspensions in solvent CFC-113. The extent of deposition onto different inhaler components, such as the aluminium alloy canister, Teflon coated canister and the metering valve was evaluated by high-performance liquid chromatography (HPLC) of the methanol/water washings of the deposited drug(s). Changing the nature of the surface properties of the container resulted in a significant difference in the extent of deposition. The deposition of the individual drugs was found to increase as the dispersion concentration of the drug increases. However, the formulation based on a combination of the two drugs was found to show different deposition behaviour compared to the individual drug formulations. The deposition of the drugs, onto the aluminium alloy canister and the metering valve, decreases as the combined dispersion concentration of the two drug increases.

Albuterol↗
PubMed2000

The glucocorticoid receptor mediates a survival signal in human mammary epithelial cells.

Complex autocrine and paracrine signaling pathways control the multiple cycles of epithelial cell proliferation and involution characteristic of the human mammary gland. Activation of these pathways can lead to cell division, cell cycle arrest, apoptosis, or survival; their aberrant regulation often contributes to malignant transformation. In this report, we show that glucocorticoid signals a potent survival pathway in the immortalized human mammary epithelial cell line MCF10A. Withdrawal of glucocorticoid from defined media triggers apoptosis, despite the presence of epidermal growth factor and insulin. Apoptosis is accelerated by ectopic expression of c-Myc and blocked by overexpression of Bcl2. Although MCF10A cells can undergo apoptosis after CD95/Fas receptor activation, cell death caused by glucocorticoid withdrawal is independent of CD95/ Fas receptor signaling. The mechanism through which glucocorticoid inhibits apoptosis is also independent of phosphatidylinositol 3-kinase activity and its downstream target Akt, thus establishing the existence of a novel epithelial cell survival pathway mediated by glucocorticoids.

Apoptosis↗
PubMed2000

A comparison of microsatellite instability in early onset gastric carcinomas from relatively low and high incidence European populations.

We have investigated the genetic basis of gastric carcinomas occurring in patients aged under 40 years from a Portuguese population with a relatively high incidence of gastric cancer. We analysed a panel of 12 microsatellite loci in DNA extracted from gastric carcinomas arising in 16 patients aged 24-39 years from Braga, Portugal. Overall, microsatellite instability (MI) in at least 1 locus was detected in 44% (7 of 16) of carcinomas. A single patient demonstrated a mutator phenotype suggestive of the hereditary nonpolyposis colorectal cancer syndrome with instability in 82% of loci. This carcinoma showed loss of expression of the hMLH1 mismatch repair protein. In a previous study, we found no evidence of MI among 10 cases of early onset gastric carcinomas from an English population, which has a relatively low incidence of gastric cancer. Comparing the 2 series, we found that there was a significant difference (p = 0.04) in the prevalence of MI (at least 1 marker affected). This geographical difference in low-level MI may be related to a significantly higher prevalence of background chronic atrophic gastritis (8 of 16 vs. 0 of 8) and Helicobacter pylori infection (15 of 16 vs. 2 of 8) in Portuguese carcinomas compared with English cases. Genetic mechanisms underlying the hereditary non-polyposis colorectal cancer syndrome may play a role in a small number of early onset gastric carcinomas. The difference in prevalence of low-level MI between these relatively high and low incidence European populations requires further investigation.

Adult↗
PubMed2000

Presence of 22q11 deletion in postadenoidectomy velopharyngeal insufficiency.

BACKGROUND: Velopharyngeal insufficiency is an uncommon complication of adenoidectomy. Persistent velopharyngeal insufficiency following adenoidectomy (VIA) may occur in association with an unrecognized syndrome, such as velocardiofacial syndrome (VCFS). Although the diagnosis of VCFS is primarily a clinical one, a test has been developed to identify the underlying chromosomal abnormality, ie, deletion of 22q11. OBJECTIVE: To describe characteristics and occurrence of the 22q11 deletion in a population with VIA. SETTING: Three tertiary referral centers. DESIGN: Retrospective case series of 23 patients with VIA who required intervention and had follow-up for more than 1 year. These patients' medical records were reviewed for indications for adenoidectomy, the presence of 22q11 deletion and whether a 22q11 deletion test was obtained, phenotypic evidence for VCFS, presence of a submucous cleft palate, velopharyngeal closure pattern, and type of speech intervention. RESULTS: Of the 23 patients, 9 underwent adenoidectomy for otitis media, 9 for obstructive sleep symptoms, and 5 for sinusitis therapy. Fourteen of the 23 patients were tested for a 22q11 deletion. Of these 14 patients, 9 had a 22q11 deletion with 5 having phenotypic evidence for VCFS. Six of the 23 patients had a submucous cleft palate, 2 of whom had a 22q11 deletion. CONCLUSIONS: Although VIA is uncommon, its occurrence should alert the otolaryngologist to the possibility of an underlying syndrome diagnosis. The 22q11 deletion test is beneficial in diagnosing patients with genotypic, but not phenotypic, VCFS in this population. In tested subjects of our patient population, 28% (4 patients) had the genotype for VCFS, without clinical evidence of VCFS.

Adenoidectomy↗
PubMed2000

A new method for identifying antibiotic-treated infections using automated pharmacy records.

For research purposes, there are few alternatives to costly surveillance for ascertaining infections in community populations. We propose a new approach based on antibiotic prescription fills in automated pharmacy records of the Group Health Cooperative of Puget Sound, in Seattle, Washington, to identify treated infections in postmenopausal women. After excluding probable antimicrobial prophylaxis and chronic antibiotic use, four intervals between antibiotic fills (30, 45, 60, and 90 days) were tested for their ability to detect new infections. Concordance with outpatient medical record reviews was evaluated in 150 women. The sensitivity of the automated pharmacy records using the four cutpoints for detecting new infections ranged from 88 to 80%, from 30 to 90 days, respectively. Of the 81 women with no infection in the chart reviews, 75% also had no infection using the pharmacy method. Good agreement was found between the two methods for counts of infections per person over the 2-year follow-up, with the 60-day cutpoint showing the greatest overall agreement with chart reviews (kappa = 0.55). The pharmacy method presented here offers a useful new approach for infection ascertainment for epidemiologic research.

Aged↗
PubMed2000

Effects of tumour necrosis factor-alpha and inhibition of protein kinase C on glucose uptake in L6 myoblasts.

Clinical and experimental studies have implicated high circulating levels of the cytokine tumour necrosis factor-alpha (TNF-alpha) in the pathogenesis of insulin resistance, not only in obesity and diabetes, but also in clinical conditions associated with cachexia and sepsis. TNF-alpha impairs insulin-mediated glucose uptake in adipocytes, but because of lipolytic effects the interpretation of clinical studies and the extent to which TNF-alpha affects muscle insulin sensitivity are unclear. In addition, protein kinase C (PKC) has recently been implicated in the mechanism of TNF-alpha-induced insulin resistance. The present study investigated the effects of TNF-alpha and a PKC inhibitor (RO-318220) on basal and insulin-stimulated 2-[(3)H]deoxyglucose uptake in cultured L6 myoblasts. Reverse transcriptase-PCR analysis confirmed that L6 myoblasts express TNF-alpha receptors I and II (p60 and p80). Dose-response curves for glucose uptake were fitted to a quadratic function to derive C(I-150) values (concentration of insulin required to increase glucose uptake by 50%). Incubation with TNF-alpha at 1 or 10 ng/ml for 24 h had no significant effect on basal glucose uptake, insulin sensitivity or maximal insulin responsiveness. C(I-150) values (means+/-S.E.M.) were as follows: basal, 91.2+/-13 nM; 1 ng/ml TNF-alpha, 102+/-12 nM; and basal, 70.8+/-13 nM; 10 ng/ml TNF-alpha, 43.7+/-40 nM. PKC inhibition markedly attenuated glucose uptake, but there was no difference in insulin sensitivity with RO-318220 alone compared with RO-318220+TNF-alpha. In conclusion, although increased TNF-alpha expression and plasma concentrations have been implicated in the pathogenesis of insulin resistance in various clinical states, there is no evidence that TNF-alpha impairs insulin-stimulated glucose uptake in a skeletal-muscle-derived cell line.

Animals↗
PubMed2000

Problems of older adults living alone after hospitalization.

OBJECTIVE: To describe functional deficits among older adults living alone and receiving home nursing following medical hospitalization, and the association of living alone with lack of functional improvement and nursing home utilization 1 month after hospitalization. DESIGN: Secondary analysis of a prospective cohort study. PARTICIPANTS: Consecutive sample of patients age 65 and over receiving home nursing following medical hospitalization. Patients were excluded for new diagnosis of myocardial infarction or stroke in the previous 2 months, diagnosis of dementia if living alone, or nonambulatory status. Of 613 patients invited to participate, 312 agreed. MEASUREMENTS: One week after hospitalization, patients were assessed in the home for demographic information, medications, cognition, and self-report of prehospital and current mobility and function in activities of daily living (ADLs) and independent activities of daily living (IADLs). One month later, patients were asked about current function and nursing home utilization. The outcomes were lack of improvement in ADL function and nursing home utilization 1 month after hospitalization. RESULTS: One hundred forty-one (45%) patients lived alone. After hospital discharge, 40% of those living alone and 62% of those living with others had at least 1 ADL dependency (P =.0001). Patients who were ADL-dependent and lived alone were 3.3 (95% confidence interval [95% CI], 1.4 to 7. 6) times less likely to improve in ADLs and 3.5 (95% CI, 1.0 to 11. 9) times more likely to be admitted to a nursing home in the month after hospitalization. CONCLUSION: Patients who live alone and receive home nursing after hospitalization are less likely to improve in function and more likely to be admitted to a nursing home, compared with those who live with others. More intensive resources may be required to continue community living and maximize independence.

Activities of Daily Living↗
PubMed2000

Clinical features, laboratory findings and management of meningococcal meningitis in England and Wales: report of a 1997 survey. Meningococcal meningitis: 1997 survey report.

OBJECTIVES: To describe the epidemiological, clinical and laboratory features of meningococcal meningitis and the effects of antibiotics on laboratory investigations under current clinical practices in England and Wales. METHODS: Using a telephone questionnaire, information was gathered on 103 cases with a clinical diagnosis of meningococcal meningitis. Included were cases with samples submitted to the Public Health Laboratory Service (PHLS), Meningococcal Reference Unit (MRU) over a 5-month period in 1997. Tests included microscopic examination, latex agglutination and culture for Neisseria meningitidis, and at MRU confirmation of identification and characterization of isolates and meningococcal polymerase chain reaction (PCR) analysis on blood and cerebrospinal fluids (CSF). RESULTS: Clinically 45% of the cases had predominantly meningitis and 55% had septicaemia and meningitis. Only 29% of the cases received pre-admission benzylpenicillin, and 66% were given antibiotics within an hour of hospital attendance. Microbiological confirmation was achieved in 97 cases, 46 (44%) by traditional tests and 92 (89%) by PCR assay, including some with both. The blood culture positive rate was 23 (22%), but in predominant meningitis the rate was only 10% (5/46). PCR was the sole method of confirmation in 48 cases. Seventy percent of the plasma samples referred were reactive by PCR assay, but all samples taken more than 24 h after hospital antibiotics were non-reactive. PCR-based techniques increased the overall number of cases with a serogroup identified by 44%. Lumbar punctures were performed in 73 of the cases and microbiological confirmation was achieved in 67 (92%) of these cases, compared to 26/30 without lumbar puncture (LP). Eighty-nine percent of the CSF samples referred were reactive by PCR; 50% of the CSF samples taken more than 24 h after hospital antibiotics were reactive, whilst none were positive by culture or microscopy. CONCLUSION: Due to variable clinical manifestations, early diagnosis and treatment was difficult. Laboratory confirmation has been improved by the introduction of PCR-based techniques. Meningococcal DNA was detected by molecular methods in CSF samples taken up to 72 h after commencement of antibiotics. During this period patients could be stabilized and the chances of complications attendant upon early LP reduced. In addition to providing accurate epidemiological information, confirming the diagnosis may alter the extent and length of follow-up.

Adolescent↗
PubMed2000

Physical inactivity and smoking increase risk for serious infections in older women.

OBJECTIVE: This study examined health and behavioral risk factors for infections that required hospitalization in postmenopausal women who were enrollees of a large health maintenance organization (HMO). METHODS: Participants were 1,365 generally healthy women aged 55 to 80 years who were followed for up to 6 years. Infection diagnoses listed first in the automated hospital discharge records were used to identify hospitalizations for which infections were the primary cause of admission. Potential risk factors for these serious infections were identified from baseline questionnaire information and automated HMO records from before baseline and during follow-up. Risks for infections associated with hospital admission were examined using multivariate logistic regression methods. RESULTS: Seventy-three women had a total of 90 hospital admissions in which infection was the primary discharge diagnosis. Behaviors that were independent predictors of infection were physical inactivity (adj. odds ratio = 4.08; 95% CI, 1.73-9.63) and smoking (adj. odds ratio = 2.64; 95% CI, 1.11-6.26). Incident cancer and lung disease were also associated with increased risk of infection. These associations were independent of age, body mass index, functional status, and other measures of health. CONCLUSIONS: Modifiable risk factors such as physical inactivity and smoking may place older women at risk for serious infections although the causal link is yet to be explained. Further research in this area may lead to new strategies aimed at reducing the serious burden of infections in the older population.

Age Factors↗
PubMed2000

Testing cyclin specificity in the exit from mitosis.

Cyclical inactivation of B-type cyclins has been proposed to be required for alternating DNA replication and mitosis. Destruction box-dependent Clb5p degradation is strongly increased in mitotic cells, and constitutive overexpression of Clb5p lacking the destruction box resulted in rapid accumulation of inviable cells, frequently multiply budded, with DNA contents ranging from unreplicated to apparently fully replicated. Loss of viability correlated with retention of nuclear Clb5p at the time of nuclear division. CLB2-Deltadb overexpression that was quantitatively comparable to CLB5-Deltadb overexpression with respect to Clb protein production and Clb-associated kinase activity resulted in a distinct phenotype: reversible mitotic arrest with uniformly replicated DNA. Simultaneous overexpression of CLB2-Deltadb and CLB5-Deltadb overexpressers similarly resulted in a uniform arrest with replicated DNA, and this arrest was significantly more reversible than that observed with CLB5-Deltadb overexpression alone. These results suggest that Clb2p and not Clb5p can efficiently block mitotic completion. We speculate that CLB5-Deltadb overexpression may be lethal, because persistence of high nuclear Clb5p-associated kinase throughout mitosis leads to failure to load origins of replication, thus preventing DNA replication in the succeeding cell cycle.

Cell Cycle↗
PubMed2000

Defective hMSH2/hMLH1 protein expression is seen infrequently in ulcerative colitis associated colorectal cancers.

BACKGROUND: Ulcerative colitis is associated with an increased risk of colorectal cancer above that of the normal population. The relative risk correlates with the extent and duration of the disease but the genetic basis of ulcerative colitis associated cancer risk is not known. AIMS: To assess the prevalence of microsatellite instability and mismatch repair gene abnormalities in ulcerative colitis associated colorectal cancer. PATIENTS: Forty six patients with colorectal cancer, with a previous histological diagnosis of ulcerative colitis. METHODS: The frequency of microsatellite instability and/or immunohistochemical expression of hMSH2 and hMLH1 was assessed. Thirty three cases were investigated using both approaches. RESULTS: Although 6/41 (14.6%) cases showed microsatellite instability at one or more markers, only one case (2. 4%) exhibited high level instability (at least two markers affected). Of 38 cases which were assessed using antibodies against hMSH2 and hMLH1, only one case (2.6%) showed loss of expression. This case, which showed loss of hMSH2 expression, was the same case which exhibited high level microsatellite instability. The 33 cases which were investigated using both approaches showed that loss of expression of either hMSH2 or hMLH1 was not seen in any case which exhibited microsatellite instability in no more than one marker. CONCLUSIONS: This study suggests that both high level microsatellite instability and loss of expression of hMSH2/hMLH1 are infrequent events in ulcerative colitis associated colorectal cancers. Low level microsatellite instability was not associated with loss of expression of either hMSH2 or hMLH1.

Biomarkers↗
PubMed2000

Histological identification of Helicobacter pylori: comparison of staining methods.

AIM: To determine whether two recently described staining methods (the modified McMullen's and the Helicobacter pylori silver stain HpSS methods) used for the histological identification of H pylori organisms are superior to two established techniques (the modified Giemsa and anti-H pylori antibody immunostain) in terms of availability, reproducibility, rapidity, sensitivity, and cost. METHODS: Histological sections from 63 paired gastric biopsies from adult patients previously investigated for dyspepsia were stained with the four methods and these were assessed blindly and independently by two observers. Of the 63 patients, 30 were originally negative in all tests for H pylori infection, 30 were positive, and the remaining three cases had discordant results using a combination of five tests (rapid biopsy urease test, urea breath test, culture, serology, and histology). RESULTS: Interobserver agreement was best with the antibody method (98%), followed by the McMullen's (90%), Giemsa (87%), and HpSS (85%). Of the 60 "gold standard" positive and negative cases, 30 were positive by the modified Giemsa stain, 29 by the McMullen's method, 29 by HpSS, and 30 by the antibody stain. However, there were two false positives with the HpSS method. The modified Giemsa is the cheapest and easiest to perform technically. CONCLUSIONS: When H pylori are present, careful examination will almost always reveal them, whichever of these stains is used. However, the modified Giemsa stain is the method of choice because it is sensitive, cheap, easy to perform, and reproducible.

Adult↗
PubMed2000

Clinicians' attitudes to recruitment to randomised trials in cancer care: a qualitative study.

OBJECTIVES: To explore attitudes to and problems experienced with recruitment into randomised trials in cancer care. METHODS: In-depth semi-structured interviews with a purposive sample of 20 hospital clinicians in the South West of England identified from 192 participants in a larger postal survey. Interviews were recorded on audiotape and fully transcribed. Data were analysed by comparing transcripts and describing emergent themes. RESULTS: Clinicians do not always find it easy to identify key randomised trials in their area of interest. Even when they identify those trials in which they would like to participate, they are not always able to recruit patients. Although recruitment can be hindered by the time and administration involved and the resources needed, the attitudes of clinicians to research in general, the design of randomised trials, clinicians' concerns regarding individual patients and patients' preferences for different treatments also present major barriers. Other factors of concern include the imposition of strict eligibility criteria and the expense and complexity of monitoring and follow-up. CONCLUSION: Barriers to recruitment depend on the clinicians' individual situations and on a complex combination of factors. Action is needed to promote awareness of randomised trials under way, to ensure that trials address issues of importance, are acceptable to patients and clinicians, and that practical support is provided for participating centres.

Attitude of Health Personnel↗
PubMed2000

Possible interactions between angiotensin II and insulin: effects on glucose and lipid metabolism in vivo and in vitro.

Angiotensin II (ANGII) increases insulin sensitivity in diabetic and non-diabetic subjects, even at subpressor doses, and because there is 'crosstalk' between ANGII and insulin-signaling pathways the underlying mechanism may not be due solely to changes in regional blood flow. A series of experimental studies was undertaken to evaluate the effects of ANGII on glucose and lipid metabolism in vivo and in vitro. Groups of fructose-fed, insulin-resistant Sprague-Dawley (SD) rats were pre-treated with 0.3 mg/kg per day of the AT(1)-receptor antagonist L-158 809 (n=16), or vehicle (n=16), by oral gavage. This was prior to an oral glucose tolerance test (day 5) and measurement of the effects of ANGII infusion (20 ng/kg per min i.v. for 3 h) on whole-body insulin sensitivity using the insulin suppression test (day 7). The effect of ANGII infusion on total triglyceride secretion rate (TGSR) was evaluated in normal SD rats pretreated for 7 days with L-158 809 (n=12) or vehicle (n=12). AT(1)- and AT(2)- receptor mRNA expression and [(3)H]2-deoxyglucose uptake were assessed in cultured L6 myoblasts. Short-term treatment with L-158 809 had no effect on glucose tolerance or fasting triglyceride levels in fructose-fed rats. ANGII infusion had no effect on insulin sensitivity in fructose-fed rats pretreated with vehicle (steady-state plasma glucose (SSPG) values 8.1+/-1.6 vs 8. 4+/-0.4 mmol/l), but pretreatment with L-158 809 resulted in ANGII having a modest insulin antagonist effect in this insulin-resistant model (SSPG values 9.6+/-0.3 vs 7.1+/-0.6, P<0.03). ANGII infusion had no significant effect on TGSR (e.g. 24.6+/-1.4 vs 28.4+/-0.9 mg/100 g per h in vehicle-treated animals). RT-PCR analysis showed that L6 cells express both AT(1)- and AT(2)-receptor mRNA. Incubation with ANGII (10(-9) and 10(-8) M) had no significant effect on the dose-response curve for insulin-stimulated [(3)H]2-deoxyglucose uptake. For example, C(I200) values (dose of insulin required to increase glucose uptake by 200%) were 4.5 x 10(-9) M (control) vs 3.9 x 10(-9) M and 6.2 x 10(-9) M, whereas the positive control (glucagon-like peptide-1) increased insulin sensitivity. Thus, ANGII infusion may have a modest insulin antagonist effect on glucose disposal in insulin-resistant fructose-fed rats pretreated with an AT(1)-blocker, but ANGII has no effect on TGSR or in vitro glucose uptake in L6 myoblasts. These findings are relevant to recent clinical discussions about the metabolic effects of ANGII and renin-angiotensin system blockade.

Analysis of Variance↗
PubMed1999

Identification of the genes responsive to etoposide-induced apoptosis: application of DNA chip technology.

DNA chip technology was used in an attempt to identify target genes responsible for apoptosis induced by etoposide, a p53 activating topoisomerase II inhibitor used clinically as an antitumor agent. 62 Individual mRNAs whose mass changed significantly were identified after screening oligonucleotide arrays capable of detecting 6591 unique human mRNA species. 12 (Nine induced and three repressed) of the etoposide-responsive genes were further studied by Northern analysis and an agreement rate of 92%, was reached. Among the 12 genes studied, two (WAF1/p21 and PCNA) are known p53 regulatory genes, two (glutathione peroxidase and S100A2 calcium-binding protein) appear to be the novel p53 target genes and the others appear to be p53-independent. Based upon these findings, the signalling pathways that possibly mediate etoposide-induced apoptosis are proposed.

Apoptosis↗
PubMed1999

No change in O2 saturation but measurable difference in thenar flexor power after radial artery harvest.

OBJECTIVES: Objective measures of morbidity will be required to establish the radial artery (RA) as a viable long term alternative to saphenous vein. The RA is the dominant arterial supply to the thenar musculature. We hypothesised that RA harvest should decrease O2 saturation and thenar muscle power. METHODS: RA was harvested from non-dominant (ND) limbs only (left n = 58, right n = 21). Oximeter values of O2 saturation were taken from the thumb of the dominant (D) and non-dominant (ND) limb pre and post operatively. A syringe filled with 25 cc of air is emptied against a one way valve connected to a pressure generator MX 100 by MEDEX, Inc, Ohio, USA. Three measures of thenar flexor power (TFP) were taken and mean values obtained in the ND and D limbs. RESULTS: O2 saturation ranged from 92 to 98% in the thumb of the ND limbs 24 h post RA harvest. The values for TFP (mean +/- SD) were 1246 +/- 246 mmHg (ND) and 1240 +/- 258 mmHg (D) pre-operatively and 1216 +/- 250 (ND) and 1259 +/- 233 (D) post operatively. The changes in TFP between the ND and D limbs (37.0 +/- 60.6 ND and 1.86 +/- 65.9 D) were significant for the D against the ND limb (P < 0.001). This reduction in TFP for the harvested limb was also found when considering handedness (28.0 +/- 24.2 and 40.3 +/- 69.2 for the left and right handed patients respectively). CONCLUSION: Our findings confirm the hypothesis that there are objective differences in TFP pre and post RA harvest at 3 months. Further studies are required to assess the clinical significance and persistence of the loss of TFP.

Adult↗
PubMed1999

Specialization and targeting of B-type cyclins.

The B-type cyclins of S. cerevisiae are diversified with respect to time of expression during the cell cycle as well as biological function. We replaced the early-expressed CLB5 coding sequence with the late-expressed CLB2 coding sequence, at the CLB5 locus. CLB5::CLB2 exhibited almost no rescue of clb5-specific replication defects, although it could rescue clb1 clb2 lethality, and in synchronized cells Clb2p-associated kinase activity from CLB5::CLB2 rose early in the cell cycle, similar to that of Clb5p. Mutagenesis of a potential substrate-targeting domain of CLB5 reduced biological activity without reducing Clb5p-associated kinase activity. Thus, Clb5p may have targeting domains required for CLB5-specific biological activity.

Cell Cycle↗