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Biomedical subjects

L Moore

Publications and source records attributed to L Moore.

At least 55 records · Page 3Linked to original sources
PubMed1999

Neoadjuvant hormonal therapy before radical prostatectomy and risk of prostate specific antigen failure.

PURPOSE: To date there is little information on the long-term effect of neoadjuvant hormonal therapy on prostate cancer progression. We performed a prospective study to determine whether patients with prostate cancer receiving neoadjuvant hormonal therapy before radical prostatectomy (hormonal therapy group) have a lower risk of prostate specific antigen (PSA) failure than those treated with radical prostatectomy alone (prostatectomy group). We also evaluated whether type of neoadjuvant hormonal therapy and duration were associated with the risk of PSA failure. MATERIALS AND METHODS: We followed 680 men initially treated for prostate cancer with radical prostatectomy between January 1988 and December 1997 at our university hospital. Of the patients 292 received neoadjuvant hormonal therapy. Median followup was 38 months. Cox regression analysis was used to assess the association between neoadjuvant hormonal therapy and PSA failure (greater than 0.3 ng./ml.) controlling for age, clinical stage, grade, initial PSA and adjuvant therapies. RESULTS: Surgical margins were positive less often in the hormonal therapy (25%) than the prostatectomy (47%) group (p = 0.0001). PSA failure was observed in 163 patients and the 5-year failure rate was 33%. No difference in risk of PSA failure was observed overall between the hormonal therapy and prostatectomy groups (hazards ratio 0.94, 95% confidence interval 0.68 to 1.30). Treatments with antiandrogen alone for any duration, and those combining antiandrogen and luteinizing hormone-releasing hormone analogue for 3 months or less were not associated with improved survival. However, patients receiving combined therapy for more than 3 months had a significantly lower risk of PSA failure than those treated with radical prostatectomy alone (hazards ratio 0.52, 95% confidence interval 0.29 to 0.93). CONCLUSIONS: Prolonged neoadjuvant hormonal therapy combining antiandrogen and luteinizing hormone-releasing hormone analogue may improve disease-free survival after radical prostatectomy.

Adult↗
PubMed1999

Prognostic value of the proliferative index determined by Ki-67 immunostaining in superficial bladder tumors.

The biological behavior of urothelial carcinomas remains unpredictable. The objective of this study was to determine the prognostic value of Ki-67 index in superficial papillary bladder tumors and to correlate it with the S-phase fraction (SPF) measured by flow cytometry. Three hundred nineteen patients with newly diagnosed superficial (pTa, pT1) bladder tumors were included between September 1990 and April 1992. Patients with bladder carcinoma in situ alone were excluded. We observed 255 pTa tumors and 64 pT1 tumors, whereas 111 lesions were classified as grade G1 and 208 as grade G2-G3. Ki-67 immunostaining was performed on paraffin-embedded material using a 3-step immunoperoxidase procedure with the murine monoclonal antibody MiB1. The relation between Ki-67 expression and prognostic variables (stage, grade, tumor size, multifocality, age, and sex) was investigated by the chi-square test. Cox regression was used to describe the association between Ki-67 and tumor recurrence in 308 patients with follow-up while adjusting for potentially confounding prognostic variables. The frequency of high Ki-67 expression (> or =10%) increased with stage (P = .005) and grade (P = .001), but not with tumor size or multifocality. Two hundred one patients experienced tumor recurrence in a median follow-up of 68 months. Stage, grade, tumor size, and multifocality were all independent predictors of recurrence. Ki-67 index greater than 10% was found to be an independent predictor of tumor recurrence among patients with tumors larger than 3 cm in diameter (HR = 2.05, CI = 1.18-3.55), but not those with smaller size tumors. With regards to the DNA index, a significant but weak correlation was observed between Ki-67 expression and the SPF (Spearman's correlation coefficient = 0.23, P = .004). In addition, aneuploid tumors had significantly higher expression of Ki-67 (22.5%) than diploid tumors (10.1%) (P = .0006). Moreover, patients with DNA aneuploid bladder tumors were more likely to have more than 10% Ki-67-positive cells than those with diploid tumors. In patients with newly diagnosed pTa or pT1 bladder tumors, a Ki-67 index above 10% is an independent predictor of shorter time to recurrence only in those with tumors larger than 3 cm.

Aged↗
PubMed1999

Dietary fat and prostate cancer survival.

OBJECTIVES: Relationships between dietary factors and the incidence of prostate cancer have emerged from epidemiologic and laboratory studies, but there are no published data on the relationship between diet and disease progression among prostate cancer patients. We studied the association between dietary fat intake and prostate cancer survival. METHODS: We prospectively followed 384 men diagnosed with prostate cancer between 1990 and 1992 in the Quebec City area. On average 3 months following diagnosis, trained nutritionists interviewed the men on their usual diet using a diet history questionnaire. Deaths during follow-up were documented through record linkage with the provincial mortality file and review of hospital records. Cox proportional hazard models were used to estimate the relative risk of dying from prostate cancer associated with terciles of fat intake, expressed as percent of dietary energy, while controlling for prognostic factors and total energy. RESULTS: The median duration of follow-up was 5.2 years. During the follow-up period 32 patients died of prostate cancer and 39 died of other causes. After controlling for grade, clinical stage, initial treatment, age and total energy intake, we found that saturated fat consumption was significantly associated with disease-specific survival (two-sided p-value = 0.008). Compared to men in the lower tercile of saturated fat, those in the upper tercile had three times the risk of dying from prostate cancer (relative risk = 3.1, 95% confidence interval: 1.3-7.7). CONCLUSIONS: Our findings suggest that saturated fat is related to disease-specific survival and that, if this relation is causal, a moderate reduction of its intake might reduce the risk of dying from prostate cancer.

Aged↗
PubMed1999

Barrier formation in the human fetus is patterned.

We recently demonstrated patterned stratum corneum maturation and skin barrier formation during fetal development in rodents and rabbit. The presence of skin patterning in these mammals led us to predict patterned barrier formation during human infant development. Here we extend our mammalian study and demonstrate patterned stratum corneum development and skin barrier formation in the pre-term human infant. Surprisingly, we show initiation of human barrier regionally as early as 20-24 wk gestational age (22-26 wk menstrual age), bringing barrier formation close to the time of periderm disaggregation. We use the mouse model to show that patterns of periderm disaggregation mirrors barrier formation. Periderm disaggregation follows and recapitulates barrier pattern, suggesting a relationship between the processes. This work reveals regional patterning in skin maturation and barrier formation in the human infant and demonstrates that initiation of human skin barrier formation in utero coincides with the current lower limit of viability of the pre-term infant.

Animals↗
PubMed1999

In vivo analysis of the domains of yeast Rvs167p suggests Rvs167p function is mediated through multiple protein interactions.

Morphological changes during cell division in the yeast Saccharomyces cerevisiae are controlled by cell-cycle regulators. The Pcl-Pho85p kinase complex has been implicated in the regulation of the actin cytoskeleton at least in part through Rvs167p. Rvs167p consists of three domains called BAR, GPA, and SH3. Using a two-hybrid assay, we demonstrated that each region of Rvs167p participates in protein-protein interactions: the BAR domain bound the BAR domain of another Rvs167p protein and that of Rvs161p, the GPA region bound Pcl2p, and the SH3 domain bound Abp1p. We identified Rvs167p as a Las17p/Bee1p-interacting protein in a two-hybrid screen and showed that Las17p/Bee1p bound the SH3 domain of Rvs167p. We tested the extent to which the Rvs167p protein domains rescued phenotypes associated with deletion of RVS167: salt sensitivity, random budding, and endocytosis and sporulation defects. The BAR domain was sufficient for full or partial rescue of all rvs167 mutant phenotypes tested but not required for the sporulation defect for which the SH3 domain was also sufficient. Overexpression of Rvs167p inhibits cell growth. The BAR domain was essential for this inhibition and the SH3 domain had only a minor effect. Rvs167p may link the cell cycle regulator Pcl-Pho85p kinase and the actin cytoskeleton. We propose that Rvs167p is activated by phosphorylation in its GPA region by the Pcl-Pho85p kinase. Upon activation, Rvs167p enters a multiprotein complex, making critical contacts in its BAR domain and redundant or minor contacts with its SH3 domain.

Cytoskeletal Proteins↗
PubMed1999

Psychological stress and incidence of ischaemic heart disease.

BACKGROUND: We assessed the relationship between psychological stress and ischaemic heart disease (IHD) incidence in a population of 868 men over a 10-year follow-up period. METHODS: In 1981, 869 men aged 42-60, free from IHD and living around Quebec City completed a questionnaire assessing the presence of psychological stress in different areas of their life. They also underwent a medical examination and provided information on IHD risk factors. From 1981 to 1991, the incidence of IHD events was ascertained. The relationship between 13 stress dimensions and IHD incidence was investigated using Cox regression while controlling for important IHD risk factors. Cross-sectional analyses were also performed to investigate the relationship between stress dimensions and IHD risk factors. RESULTS: Between 1981 and 1991, 79 men (9%) experienced a first IHD event. The following risk factors were associated with the risk of IHD: age, (rate ratio (RR) = 1.93, 95% CI: 1.21-3.09), hypertension (RR = 1.90, 95% CI: 1.22-2.98), triglycerides (RR = 1.87, 95% CI: 1.19-2.95) and high density lipoprotein (HDL) cholesterol (RR = 1.64, 95% CI: 1.05-2.55). After controlling for risk factors, not one of the psychological stress dimensions significantly altered the risk of IHD. CONCLUSIONS: While confirming the influence of hypertension, age, triglycerides and HDL cholesterol on IHD incidence, this study suggests that there is no important connection between the explored stress dimensions and IHD incidence. It is unlikely that this lack of association is due to the stress questionnaire since the 13 stress dimensions were rigorously developed through independent evaluation of the questions by three specialists and many statistically significant relationships were observed between stress dimensions and IHD risk factors.

Adult↗
PubMed1999

FSH-induced resumption of meiosis in mouse oocytes: effect of different isoforms.

The ability of different isoforms of follicle stimulating hormone (FSH) to induce the resumption of meiosis in cultured mouse oocytes was evaluated. Oocytes were cultured in the presence of hypoxanthine to prevent spontaneous resumption of meiosis. Using serial dilutions of the isoform fractions representing less acidic isoforms (pI 6. 43-5.69), mid-acidic (pI 5.62-4.96) and acidic (pI 4.69-3.75), the concentration which caused 50% of the oocytes to resume meiosis and undergo germinal vesicle breakdown (GVBD) after a culture period of 24 h (i.e. ED(50%) GVBD) was determined. The FSH concentration of the isoform fractions was determined by radioimmunoassay, radio-receptor assay or through cAMP release in a Chinese hamster ovary-cell line expressing the human FSH-receptor. Determined by radioimmunoassay, the (ED(50%) GVBD) values were: less acidic 6.4 +/- 0.3 IU/l (mean +/- SD), mid-acidic 6.1 +/- 0.7 IU/l and acidic 12.2 +/- 0.7 IU/l. The less and mid-acidic isoforms were significant lower than the acidic (P < 0.0005). Similar relationships between the isoform fractions were obtained by the two other FSH assays. The results demonstrate that FSH isoforms with a pI of >5.0 induced resumption of meiosis significantly more efficiently than acidic isoforms. Less and mid-acidic isoforms may exert an important physiological function by inducing the resumption of meiosis in oocytes from pre-ovulatory follicles during the mid-cycle gonadotrophin surge.

Animals↗
PubMed1999

Preclinical toxicity screening of intrathecal adenosine in rats and dogs.

BACKGROUND: Intrathecally administered adenosine receptor agonists have antinociceptive effects in animals, suggesting that intrathecal adenosine might provide analgesia in humans. The authors performed preclinical neurotoxicity studies to define the safety of intrathecally administered adenosine in rats and dogs. METHODS: Eighteen rats with long-term intrathecal catheters received daily injections of saline or 100 microg adenosine for 4 days and were observed for general behavior and thermal nociception before being killed on day 6. Nine beagle dogs were prepared with long-term, lumbar intrathecal catheters and infused continuously with saline or adenosine, 2.4 mg/day for 48 h, then 7.2 mg/day for 26 days. Animals were then anesthetized and perfused with preservative and their spinal cords were examined systematically. RESULTS: No disturbances in neurologic function were detected in either animal species. intrathecal adenosine caused transient sedation in rats and increased muscle tone in dogs, resolving with continued exposure to drug. Neither adenosine-nor saline-treated rats or dogs showed acute thermal analgesia. Adenosine groups did not differ from saline groups regarding histopathology, although a moderate fibrotic and inflammatory reaction was noted in both, and protein concentrations in cerebrospinal fluid were increased in both. CONCLUSION: The current study in rats and dogs failed to provide behavioral or histologic evidence of neurotoxicity from intrathecal administration of adenosine. This provides evidence for the presumption of safety of adenosine in this dose range, and supports phase I safety trials of acute intrathecal adenosine administration in humans.

Adenosine↗
PubMed1999

Helicobacter pylori treatment and antibiotic susceptibility: results of a five-year audit.

BACKGROUND: Helicobacter pylori eradication treatment has been a rapidly evolving field. Audit of treatment results provides reassurance that trial data can be translated into routine clinical practice. METHODS: Data were collected prospectively over five years. Patients were given four different treatment regimens over the audit period 'standard' triple therapy, two types of clarithromycin-based treatment or ranitidine, amoxycillin and metronidazole. Eradication was proven by a urea breath test at least four weeks after completing treatment. RESULTS: Eradication treatment for H. pylori was given to 665 patients; 89% had follow-up data. H. pylori eradication was significantly associated with treatment type (p<0.0001) and smoking (p=0.04) by univariate analysis, but was not associated with sex, age, alcohol consumption, endoscopic diagnosis, recent treatment with anti-secretory drugs or NSAIDs. By logistic regression analysis, only treatment type was significant (p=0.0001). H. pylori culture and sensitivities were available for 255 patients. Metronidazole resistance was shown for 84 isolates (32%) and clarithromycin resistance for 18 isolates (6.8%). Metronidazole resistance was significantly associated with younger age (p=0.02), ethnicity (p=0.02), female sex (p=0.02), and year of endoscopy (p=0.04), but was not associated with clarithromycin resistance. Clarithromycin resistance was not associated with age, sex, or ethnicity. Metronidazole resistance significantly affected H. pylori eradication for regimens containing metronidazole without clarithromycin. Eradication with metronidazole without clarithromycin was achieved in 90% of sensitive strains but only 55% of resistant strains (p<0.001). Metronidazole resistance was not significantly associated with treatment failure when metronidazole was combined with clarithromycin. Eradication with metronidazole and clarithromycin was achieved in 86% of sensitive strains and 78% of resistant strains (p=0.42). CONCLUSION: Treatment type and antibiotic susceptibility are the most important determinants of treatment success.

Adolescent↗
PubMed1999

Regulation of transcription at the Saccharomyces cerevisiae start transition by Stb1, a Swi6-binding protein.

In Saccharomyces cerevisiae, gene expression in the late G(1) phase is activated by two transcription factors, SBF and MBF. SBF contains the Swi4 and Swi6 proteins and activates the transcription of G(1) cyclin genes, cell wall biosynthesis genes, and the HO gene. MBF is composed of Mbp1 and Swi6 and activates the transcription of genes required for DNA synthesis. Mbp1 and Swi4 are the DNA binding subunits for MBF and SBF, while the common subunit, Swi6, is presumed to play a regulatory role in both complexes. We show that Stb1, a protein first identified in a two-hybrid screen with the transcriptional repressor Sin3, binds Swi6 in vitro. The STB1 transcript was cell cycle periodic and peaked in late G(1) phase. In vivo accumulation of Stb1 phosphoforms was dependent on CLN1, CLN2, and CLN3, which encode G(1)-specific cyclins for the cyclin-dependent kinase Cdc28, and Stb1 was phosphorylated by Cln-Cdc28 kinases in vitro. Deletion of STB1 caused an exacerbated delay in G(1) progression and the onset of Start transcription in a cln3Delta strain. Our results suggest a role for STB1 in controlling the timing of Start transcription that is revealed in the absence of the G(1) regulator CLN3, and they implicate Stb1 as an in vivo target of G(1)-specific cyclin-dependent kinases.

Blotting, Western↗
PubMed1999

Dietary fat and prostate cancer progression and survival.

BACKGROUND: The association between dietary factors and the occurrence of prostate cancer has been studied extensively, but there is, as yet, no published study on the relationship between diet and disease progression among prostate cancer patients. We studied the association between dietary fat intake and prostate cancer survival. METHODS: We prospectively followed 384 men diagnosed with prostate cancer between 1990 and 1992 in the Quebec City area who participated in a case-control study of diet in relation to prostate cancer occurrence. Trained nutritionists interviewed the men on their usual diet using a diet history questionnaire. Deaths in the follow-up were documented through record linkage with the provincial mortality file and review of hospital records. The cause of death was taken as written on the death certificate. Cox proportional hazards models were used to estimate the relative risk of dying from prostate cancer associated with terciles of fat intake, expressed as percent of dietary energy, while controlling for prognostic factors and total energy. RESULTS: The median duration of follow-up was 5.2 years. During the follow-up period, 32 patients died of prostate cancer and 39 died of other causes. The 5-year disease-specific survival was 91%. After controlling for grade, clinical stage, initial treatment, age and total energy intake, we found that saturated fat consumption was significantly associated with disease-specific survival (p = 0.008). Compared to men in the lower tercile of saturated fat, those in the upper tercile had three times the risk of dying from prostate cancer (hazards ratio 3.13, 95% confidence interval 1.28-7.67). CONCLUSION: Our findings suggest that, if saturated fat is causally related to disease-specific survival, a moderate reduction of its intake below 10% of energy should reduce the risk of dying from prostate cancer. This dietary goal is already recommended for health promotion and primary prevention of heart disease and cancer.

Aged↗
PubMed1999

The trithorax group gene osa encodes an ARID-domain protein that genetically interacts with the brahma chromatin-remodeling factor to regulate transcription.

The trithorax group gene brahma (brm) encodes the ATPase subunit of a chromatin-remodeling complex involved in homeotic gene regulation. We report here that brm interacts with another trithorax group gene, osa, to regulate the expression of the Antennapedia P2 promoter. Regulation of Antennapedia by BRM and OSA proteins requires sequences 5' to the P2 promoter. Loss of maternal osa function causes severe segmentation defects, indicating that the function of osa is not limited to homeotic gene regulation. The OSA protein contains an ARID domain, a DNA-binding domain also present in the yeast SWI1 and Drosophila DRI proteins. We propose that the OSA protein may target the BRM complex to Antennapedia and other regulated genes.

Animals↗
PubMed1999

The Drosophila kismet gene is related to chromatin-remodeling factors and is required for both segmentation and segment identity.

The Drosophila kismet gene was identified in a screen for dominant suppressors of Polycomb, a repressor of homeotic genes. Here we show that kismet mutations suppress the Polycomb mutant phenotype by blocking the ectopic transcription of homeotic genes. Loss of zygotic kismet function causes homeotic transformations similar to those associated with loss-of-function mutations in the homeotic genes Sex combs reduced and Abdominal-B. kismet is also required for proper larval body segmentation. Loss of maternal kismet function causes segmentation defects similar to those caused by mutations in the pair-rule gene even-skipped. The kismet gene encodes several large nuclear proteins that are ubiquitously expressed along the anterior-posterior axis. The Kismet proteins contain a domain conserved in the trithorax group protein Brahma and related chromatin-remodeling factors, providing further evidence that alterations in chromatin structure are required to maintain the spatially restricted patterns of homeotic gene transcription.

Amino Acid Sequence↗
PubMed1999

Downward trend in prostate cancer mortality in Quebec and Canada.

PURPOSE: If new treatment strategies and screening for prostate cancer are effective they should reduce prostate cancer mortality. In this review we monitored prostate cancer mortality rates in Quebec and in Canada. MATERIALS AND METHODS: We obtained data on all deaths from prostate cancer between 1976 and 1997 in Quebec, and 1976 and 1996 in Canada. We calculated age standardized mortality rates and assessed changes with time. RESULTS: Prostate cancer mortality rates increased regularly until 1991 in Quebec and Canada. After 1991 the rates decreased moderately until 1995 and then more markedly in 1996. There was a further decline in 1997 in Quebec. Overall, age standardized prostate cancer mortality rates declined by 23% in Quebec between 1991 and 1997, and by 9.6% in Canada between 1991 and 1996. The mortality decline was observed for all age groups but was more pronounced among men younger than 75 years. CONCLUSIONS: Until 1995 the trends in prostate cancer mortality in Quebec and Canada were similar to those observed in the United States. Our data suggest that a sharper decline has occurred since 1995. It is of primary importance to identify the causes of the mortality decline. As prostate cancer mortality rates declined relatively early after the initiation of widespread screening with prostate specific antigen, it is unlikely that screening has as yet contributed in a major way to the decline. It is more likely that the mortality reduction is a consequence of better prostate cancer management or improved treatment modalities.

Age Distribution↗
PubMed1999

Peer consultation reflection exercise.

OBJECTIVE: To explore participants' overall perception of the value of the Peer Consultation Reflection Exercise (PCRE); of barriers and facilitators to participation and learning during a PCRE; and of the transferability of the experience to participants' own settings. DESIGN: This study used the qualitative techniques of key informant interviews and a focus group. SETTING: Focus group and key informant interviews at the 1996 Annual Meeting of the College of Family Physicians of Canada's Section of Teachers. PARTICIPANTS: Family medicine teachers attending a PCRE. METHOD: Five key informant interviews and one focus group composed of five participants were conducted to explore participants' experience of participating and learning during a PCRE. MAIN FINDINGS: Participants viewed the PCRE as a valuable opportunity to interact and learn from colleagues a were especially impressed with the opportunity to listen. Confidentiality and the important role of the facilitator were identified as key components. The greatest perceived barrier was the formal structure of the PCRE. CONCLUSIONS: The PCRE is an innovative strategy for personal and professional development. It could be used in other settings.

Adult↗
PubMed1999

Predictive value of cell cycle markers p53, MDM2, p21, and Ki-67 in superficial bladder tumor recurrence.

The aim of the study was to determine whether the expression of the cell cycle markers p53, MDM2, p21, and Ki-67 was predictive of superficial bladder cancer recurrence and to compare the relative predictive power for tumor recurrence of a cell cycle index based on the number of abnormally expressed cell cycle markers with a clinicopathological index based on primary clinical tumor characteristics. The expression of p53, MDM2, and p21 proteins and the value of the Ki-67 index were analyzed for 244 patients. One hundred ninety-four lesions were determined to be superficial papillary tumors (pTa), whereas 50 tumors invaded the lamina propria (pT1). Tumor grade was noted low (grade 1) in 83 cases and high (grades 2-3) in 161 cases. An avidin-biotin peroxidase method was performed using monoclonal antibodies against p53, MDM2, p21, and Ki-67 antigens after antigen retrieval treatment of formalin-fixed specimens. The cell cycle marker index was created using the number of abnormally expressed cell cycle markers according to the following cutoff points: p53 (>5%), MDM2 (>20%), p21 (<5%), and Ki-67 (>10%). The clinicopathological index was created using the following adverse tumor characteristics: grades G2-G3, stage pT1, multifocality, and diameter of tumors > 3 cm. Cox regression models were used to calculate the relative risks and their 95% confidence intervals associated with disease recurrence for the clinicopathological index and the cell cycle marker index. The chi2 test was performed to describe the correlation between the Ki-67 index and p53, MDM2, and p21 protein expression. Kaplan-Meier survival curves were generated to demonstrate the disease-free survival according to these two prognostic indexes. The clinicopathological index was a strong, independent predictor of disease recurrence where tumors with three or four adverse tumor characteristics at initial resection had over four times the risk of recurrence than tumors with no risk factors (P for trend = 0.0001). A strong correlation was observed between the Ki-67 index >10% and both MDM2 and p21 proteins. MDM2 was overexpressed in 106 tumors (43%), and p53 was overexpressed in 47 (19%); Ki-67 was >10% in 171 cases (70%). Thirty-nine tumors (16%) were p21 negative. The risk of recurrence increased slightly with the number of abnormally expressed cell cycle markers, but when the clinicopathological index was taken into account in multivariate analysis, the cell cycle marker index was not predictive of disease recurrence (P for trend = 0.72). The cell cycle markers studied provided no added prognostic information on disease recurrence after initial resection of papillary superficial tumors when the clinicopathological parameters were taken into account.

Aged↗
PubMed1998

Interaction of yeast Rvs167 and Pho85 cyclin-dependent kinase complexes may link the cell cycle to the actin cytoskeleton.

BACKGROUND: . PHO85 encodes the catalytic subunit of a cyclin-dependent kinase (Cdk) in budding yeast and functions in phosphate and glycogen metabolism. Pho85 associated with the G1 cyclins Pcl1 and Pcl2 is also required for cell cycle progression in the absence of the Cdc28 cyclins Cln1 and Cln2. Loss of Pcl1, Pcl2 and related Pho85 cyclins results in budding defects, suggesting that Pcl-Pho85 complexes function in cell morphogenesis early in the cell cycle; their precise role is not clear, however. RESULTS: . To identify targets for Pcl-Pho85 kinases, we performed yeast two-hybrid interaction screens using Pcl2 and the related cyclin Pcl9. We identified RVS167, a gene involved in endocytosis, organization of the actin cytoskeleton, and cell survival after starvation. Like rvs167Delta mutants, pho85 mutants or strains deleted for the Pcl1,2-type Pho85 cyclins showed abnormal cell morphology on starvation, sensitivity to salt, random budding in diploids, and defects in endocytosis and in the actin cytoskeleton. Overexpression of Rvs167 in wild-type cells caused morphological abnormalities and growth arrest at high temperatures; these phenotypes were exacerbated by deleting PHO85. Rvs167 has a Src homology 3 (SH3) domain and five potential Pho85 phosphorylation sites; recombinant Rvs167 was phosphorylated by the Pcl2-Pho85 kinase in vitro. Maximal phosphorylation of Rvs167 in vivo required Pho85 and the Pcl1,2-type cyclins. CONCLUSIONS: . Rvs167 interacts with Pho85 cyclins and is implicated as a target of Pho85 kinases in vivo. Our results identify a connection between Cdks and the actin cytoskeleton; interaction of Rvs167 and Pcl-Pho85 Cdks might contribute to actin cytoskeleton regulation in response to stresses such as starvation.

Actins↗