The consequences of functional selectivity suggest that the inherent activity and toxicity profile of each individual agonist might be different and relevant to deducing what could result from idiosyncratic responses or overdose,73 but toxicity data are not usually published. Functional selectivity means that drugs that are equipotent ligands at the 5-HT2A receptor can have different

“downstream” effects.40,74 Some clinically used dopamine agonists are also agonists at the 5-HT2A receptor, eg, lisuride and pergolide. LSD and pergolide are hallucinogenic, but lisuride is not.74 There appear to be no reports of complications involving hyperthermia with these drugs. Is it just luck that they happen to exhibit the “functional selectivity” that avoids this? One might assume Panobinostat that if experimental compounds did precipitate hyperthermic toxicity they would rapidly be screened out; however, without published toxicity data doubt remains. Be that as it may, the triptans are inactive at the 2A receptor, HDAC cancer and the evidence indicates that their very weak activity at the 1A receptor is almost certainly of no relevance or consequence. Indeed, if there were to be a convincing report of definite severe hyperthermic SS with a triptan, it would be a valuable

report deserving critical evaluation. Such a case might provide insights about functional selectivity and genetic variants of receptors.75,76 It is therefore clear, in my opinion, that triptans do not pose a risk of causing severe SS for 2 reasons: (1) they do not show serotonergic side effects or toxicity by themselves or with other serotonergic drugs; (2) they do not posses the

pharmacological properties that we are confident are required to mediate SS. It is important to note that there have been clear precedents of many false-positive reports with other drugs that we know are not serotonergic and cannot precipitate SS, eg, amitriptyline, trazodone, nefazodone, and mirtazapine. These have all been analysed in detail elsewhere9,10,14,15: but there are numerous incorrect reports of supposed SS from them, so they serve to remind us of the importance of establishing the pharmacology of the drug and its ability to raise serotonin, which constitute the sine qua non for SS, and of using our knowledge of the spectrum concept of SS to Staurosporine mouse predict the serotonergic potency of drugs in humans from data about their propensity to induce SS.9 There is a great contradiction between the estimate of risk, and the conclusions and recommendations, of the USA FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA) in their respective assessments of methylene blue,77 an MAOI, see Stanford,22 and triptans. On the one hand, the MHRA fail to warn of SS despite strong evidence of severe SS, whereas the FDA does warn of “fatal” SS where no substantive evidence exists.

3b), and it showed that

Asp409del mutant dramatically changed the Na+-binding loop conformation and the Na+-binding residues (Try185 and Asp185a) in the mutant loop were off the Na+ binding sites. Therefore, Na+ binding capacity of the loop would be impaired, and the conformation of the neighbouring catalytic pocket and FVa-binding helix (residues 163–170) might be changed. The enzymatic activity of the Asp409del mutant FXa would be affected, consistent with our in vitro expression study results. In this report, we analysed a proband with this website severe FX deficiency who has experienced abnormal bleeding since childhood. Two novel heterozygous mutations were identified in the proband: one was a splice mutation (IVS5+1G>A) and the other was an in-frame deletion of aspartic acid 409 (Asp409del), which RG-7388 ic50 is associated with the CRM+ mutation. Mutations that occur in the GT-AG consensus splice sequences are certain to result in incorrect splicing, but aberrant splicing patterns are

heterogeneous, resulting in either complete skipping of the exon, retention of the intron, or introduction of a new splice site within either an exon or intron [5]. All splice sites of the F10 gene are GT-AG consensus pairs. At present, five splice-site mutations in the F10 gene have been reported, but only two have been studied using in vitro splicing and ectopic transcript analysis [3, 6]. In this study, a donor splice-site mutation in intron 5 (IVS5+1G>A)

was studied by ectopic transcription combined with informative marker analysis. The result of ectopic transcription showed that no aberrant transcript from the IVS5+1G>A mutant allele was found. Because the proband was homozygous for Fossariinae all reported polymorphisms in the F10 gene (data not shown), the heterozygous deletion (Asp409del) in exon 8 identified in the other allele was used as an informative marker, and sequencing results confirmed the loss of the transcript from the splice-site mutant allele. Therefore, the use of an informative marker in this study provided direct evidence of the absence of an aberrant transcript from the splice-site mutant. The possible reason for the absence of such a transcript might be that the mRNA derived from the IVS5+1G>A mutant allele is unstable and degrades rapidly in vivo. Therefore, a computer-assisted analysis of splice-site prediction in the DNA sequence was performed with a program available online (http://www.fruitfly.org/seq_tools/spliceAbst.html). The program predicted that the mutation might completely abolish the physiological splice site and result in two candidate splice sites with the same splice-site score of 0.83 (physiological score of 0.94). Both transcripts originating from these two alternative splice sites were predicted to possess terminal codons at nucleotide positions 82–84 of exon 6 and 111–113 of intron 5 respectively.

For example, if walruses haul out on land in late summer, after ice-based surveys are complete, lower calf:cow ratios ICG-001 molecular weight on beaches may be a consequence of calves being exposed to a constant survival rate for a longer

period of time and not due to abnormally high mortality on beach haulouts. While the estimation of calf:cow ratios provides managers with a metric than can be used to monitor the status of the Pacific walrus population, how the ratio is sampled can and should be improved upon. Therefore, we make the following recommendations: (1) Surveys need to classify 200–300 cow groups (~1,600–2,500 cows) to estimate calf:cow ratios with 20%–30% relative precision. Higher precision will require sampling more groups and surveys conducted at a different time of

year or on beaches (i.e., not on sea ice) may require differing sample sizes. (2) Tagging studies need to be conducted to determine how the haul out behavior of cows with calves differs from that of cows without calves. Estimates of the availability of cows with calves and cows without calves can be used to estimate the true calf:cow ratio. (3) Ideally, the sizes of groups classified should reflect what is available. If observers cannot selleck kinase inhibitor ensure that the distribution of group sizes sampled approximates what is available, sampling some large groups allows investigation of how the ratio may vary as a function of group size. (4) The timing of future surveys warrants careful consideration. Although we did not detect declining ratios as a function date, ratios collected across years may not be directly comparable if they are collected at different times of year, as calf mortality may confound comparisons. (5) Surveys should cover the entire ice edge and should be repeated when possible to verify that ratios are not spatial and/or temporal anomalies. Dr. Francis “Bud” Fay began developing this method to visually sample walruses in 1958 because he recognized the need for a sensitive method for monitoring HSP90 the status of the population. He would want us to thank the officers and the crews of the survey ships

and those that assisted with the field tests, especially B. P. Kelly, A. Akeya, J. J. Burns, P. Gehnrich, S. Hills, A. Hoover-Miller, M. Iya, A. Johnson, L. Lowry, E. Miller, R. Miller, R. Nelson, G. C. Ray, D. Rugh, J. Sease, A. Sorensen, and D. Wartzok. Ship support was provided by NOAA, Greenpeace, and the Soviet All-Union Institute of Fisheries and Oceanography. Additional support was provided by the University of Alaska Sea Grant Program, the Outer Continental Shelf Environmental Assessment Program, the U.S. Fish and Wildlife Service, the Minerals Management Service, and the Alaska Department of Fish and Game. B. Bolker provided helpful discussion regarding beta-binomial models. T. Gerrodette provided a useful critique of this manuscript. M. Udevitz, D. Monson, and C.

Particularly, we focused on the endoscopic findings and clinicopathological characteristics of colonic schistosomiasis. Methods: All cases with intestinal

schistosomiasis diagnosed between October 2004-October 2010 in West China Hospital were included in the study. A total of 179 cases of colonic schistosomiasis diagnosed by colonoscopy and pathological examination were collected for analysis, and the demographics, the see more presence of symptoms, endoscopic findings, clinicopathological characteristics were retrospectively evaluated. Results: Of the 179 colonic schistosomiasis patients, 32 cases (male = 24, 75%) aged 44–85 years old combined with colorectal cancer (CRC) were detected. 32 lesions

were classified as 12 as endophytic/ulcerative (37.5%), 10 as exophytic/fungating (31.2%), 4 as annular (12.5%), 3 asIIa (superficial elevated type) (9.4%), 3 asIIc (superficial depressed type) (9.4%). The segments of rectum and sigmoid colon were involved in 19 patients (59.4%) and 6 patients (18.8%), respectively. The histopathologic type was classified as follows:30 well-differentiated adenocarcinomas, one mucinous adenocarcinoma, one poorly differentiated adenocarcinomas. The pathological findings have suggested that colorectal malignancy with schistosome ova deposited. Conclusion: Chronic schistosomal infestation is a probable etiological role in promoting carcinogenesis of colorectal neoplasms. Proposing that selleck chemicals patients diagnosed as intestinal schistosomiasis undergo colonoscopy and pathological examinations regularly if necessary AMP deaminase medical infrastructures are available. Assuring the periodical administration

of anthelminthics is essential to promote the control of schistosomiasis in endemic countries. Key Word(s): 1. colonoscopy; 2. pathology; 3. colorectal carcinoma; 4. schistosomiasis; Presenting Author: SHOMRON BEN-HORIN Additional Authors: TANIA BERDICHEVSKI, NATI KELLER, GALIA RAHAV, SIMON BAR-MEIR, RAMI ELIAKIM Corresponding Author: SHOMRON BEN-HORIN Affiliations: Sheba Medical Center Objective: Although pseudomembranes are the hallmark manifestation of Clostridium difficile-associated diarrhea (CDAD), there are scant data specifically addressing their impact on the clinical outcome. We investigated whether the formation of pseudomembranes predicts a worse CDAD outcome. Methods: CDAD patients hospitalized during 2010 underwent sigmoidoscopy and were followed prospectively. In addition, all hospitalized CDAD patients in 01/2000–12/2009 who underwent lower endoscopy were retrospectively identified and their charts reviewed. Patients with detectable pseudomembranes on endoscopy were compared to those in whom pseudomembranes were absent.

Associations of HLA class II genes with DILI have also been reported

for the antituberculosis drugs isoniazid (DRB1*03), rifampin (DQA1*0102), see more and ethambutol (DQB1*0201).74 The recognition of the role of immune response regulation and universal downstream mechanisms in DILI defined related genetic variants as new targets for genetic association studies. Polymorphisms affecting the expression of the cytokine system may favor T cell–mediated immune responses, or may also promote hepatotoxicity regardless of the initial mechanism. The first CGAS that investigated IL-10 and IL-4 polymorphisms as risk factors for diclofenac-induced DILI therefore represents a conceptual landmark. This this website study found indeed that variants with low IL-10 (−627 AA/AC), and high IL-4 (−590 TT/CT) gene transcription are more frequently associated with DILI, and concluded that these may promote a T helper 2–mediated immune response to neoantigen formation.29 Another study found no association between IL-10, IL-4, and TNF-alpha variants and mixed DILI cases, but a low IL-10–producing variant was associated with DILI for subgroups of patients without peripheral blood eosinophilia and patients with serious DILI.31 Furthermore, variants of IL-6 were associated with increased aminotransferases under treatment with tacrine.75 Oxidative stress and antioxidant defense are involved

in many hepatotoxic mechanisms, including direct toxicity of reactive metabolites, upstream and downstream immune and inflammatory reactions, and MPT. Studies on DILI pharmacogenetics of oxidative stress relating to CYP450 enzymes and GST have

been discussed above. Considering the central mechanistic role of mitochondria in DILI mitochondrial manganese superoxide dismutase (SOD2) may be of particular interest because its function is essential for the scavenging of mitochondrial superoxide. Indeed, SOD2 knockout mice (SOD2 +/−) showed increased susceptibility to DILI caused by nimesulide76 Smad inhibitor and troglitazone.10 In humans, one study found that patients with a SOD2 mutant c allele have an elevated risk of DILI caused by various drugs.68 Furthermore, it may be of interest that antioxidant defense is under the master control of nuclear factor erythroid-derived 2-like (NFE2L), which has also been shown to be involved in DILI77, 78 and may therefore represent a potential target for future genetic association studies. The bile salt export pump (BSEP, ABCB11 gene) mediates the efflux of bile acids from hepatocytes into the bile canaliculus.79 Impairment of normal BSEP function results in intracellular accumulation of bile acids and consequent liver injury. Genetic variants of ABCB11 have been studied intensely in the context of various cholestatic disorders, including DILI.

Subjects Compound Library research buy using diazepam or clomethiazol were not tested until at least 7 days after their final medication. Patients with elevated ammonium levels, hypovitaminosis, hypothyroidism, electrolyte

disturbances, or parameters indicating an acute inflammation were excluded. Apart from mild dysthymia, all central nervous system (CNS)-affecting diseases, cognitive complaints and CNS-affecting drugs were further exclusion criteria. Three patients did not undergo all neuropsychological subtests for compliance reasons. The control group was closely matched by age, education, and gender. One control subject was excluded because of a previously undiagnosed major depression, and a further matched pair could not be found. The following well-established cognitive tests were performed by a senior neuropsychologist

as described in the literature: Digit Span subtest of the Wechsler Adult Intelligence Scale, Version III (WAIS-III), the two classical versions Autophagy inhibitor chemical structure of the Trail Making Test (TMT-A, TMT-B), Benton facial recognition test, Syndrom-Kurz-Test (SKT), Facially Expressed Emotion Labeling (FEEL), and a German version of the verbal learning memory test (VLMT). The Mehrfachwahl-Wortschatz-Intelligenztest (MWT-B), a multiple-choice vocabulary intelligence test, was used to provide an estimation of crystalline intelligence. The Regensburg Wortflüssigkeitstest (RWT), a word fluency test containing verbal and phonological fluency with alternating categories, was also applied. The Becks Depression Inventory, second version (BDI-II), was

completed as a self-questionnaire. All participants performed a computerized motor short-term memory paradigm. Subjects were required to memorize a 4-, 5-, or 6-item finger sequence, which was indicated by a dot moving on the fingers of a schematic of the left hand or right hand. A go cue was presented either immediately or after a 5- to 7-s pause, and the memorized finger sequence had to be reproduced DNA Damage inhibitor as quickly and accurately as possible. Each sequence length was combined with both types of delay and the two possible hands, yielding 12 distinct conditions. Each condition was presented six times throughout the whole experiment. Thus, in total, 72 trials were presented in a randomized fashion. All visual stimuli were displayed using the presentation software package (Version 12.0). A standardized finger-tapping test was performed to exclude motor dysfunction. Measurements from the neuropsychological assessment, the motor paradigm and sociodemographic data were analysed offline using MATLAB (Mathworks, Natick, MA). Group differences were analysed using two sample t-tests. Correlations were calculated by Spearman’s rank. Gender distribution was tested by a chi-square test.

Highest prevalence of NAFLD was seen among Indian and Malay males at 33.3 XL184 % and 25.5 %, respectively. The prevalence of NAFLD among Chinese males was 6.8 %. Independent factors associated with NAFLD were: age, male gender, obesity and elevated serum ALT level. Conclusion: The particularly high prevalence of NAFLD among Indian and Malay males is observed as early as young adulthood and is consistent with the higher prevalence of obesity in these groups. Key

Word(s): 1. NAFLD; 2. ethnicity; 3. young adult; 4. epidemiology; Presenting Author: WAH KHEONG CHAN Additional Authors: ALEXANDER TONG BOON TAN, SHIREENE RATNA VETHAKKAN, PEI CHIEN TAH, ANUSHYA VIJAYANANTHAN, KHEAN LEE GOH Corresponding Author: WAH KHEONG CHAN Affiliations: University of Malaya Objective: Non-alcoholic fatty liver disease (NAFLD) has been associated with increased cardiovascular diseases independent of traditional risk factors for atherosclerosis. We embarked on buy RXDX-106 this study to determine if ultrasonography-diagnosed

NAFLD is associated with prevalent ischemic heart disease (IHD) among diabetics in a hospital clinic setting. Methods: This is a cross-sectional study on consecutive patients seen at the Diabetic Clinic of University of Malaya Medical Centre. Diagnosis of NAFLD was by ultrasonography following exclusion of significant alcohol intake and other causes of chronic liver disease. The medical record for each patient was reviewed for documented IHD. Patients without documented IHD but had symptoms and/or electrocardiographic changes suggestive of IHD were referred for cardiac evaluation. Results: Data for 399 patients were analyzed. Mean age was 62.8 ± 10.5 years with 43.1% male. Mean duration of diabetes mellitus was 16.2 ± 9.7 years and mean serum HbA1c level was 8.1 ± 1.8%. NAFLD and IHD were present in 49.6% and 26.6%, respectively. Ultrasonography-diagnosed NAFLD and serum ALT and GGT levels

were not associated with IHD. The prevalence of IHD was highest among the Indians (34.1%) followed by the Malays (29.2%) and the Chinese (20.1%). No association Thymidylate synthase was found between ultrasonography-diagnosed NAFLD or serum ALT and GGT levels and IHD when analyzed according to ethnicity. On multivariate analysis, independent factors associated with IHD were older age, lower levels of physical activity, greater waist circumference and higher serum glycated hemoglobin level. Conclusion: Ultrasonography-diagnosed NAFLD was not associated with prevalent IHD among long-standing poorly-controlled diabetics. Better characterization of NALFD using non-invasive methods may allow more accurate risk stratification for cardiovascular disease. Key Word(s): 1. NAFLD; 2. IHD; 3. diabetes mellitus; Presenting Author: ROMMELPARULAN ROMANO Additional Authors: MELCHORMESA CHAN, CARMELITADADO DALUPANG, CHANDY LOUPATIAG MALONG, ABIGAIL MILO, MARIO MILO Corresponding Author: ROMMELPARULAN ROMANO Affiliations: University of Santo Tomas Hospital Objective: Background.

The hazard ratio for all-cause mortality compared with controls was 2.2, 95% CI: [1.8; 2.7], P < 0.001 for the entire group PFT�� mouse of patients and 1.7, 95% CI: [1.3; 2.2], P < 0.001 when patients with HIV and/or viral hepatitis were excluded. The corresponding figures for the severe haemophilia subgroup were 6.6, 95% CI: [4.5; 10.0], P < 0.001

and 8.2, 95% CI [3.2; 20.8], P < 0.001 respectively. The most common causes of death were related to malignancies and the haemostatic defect. People with haemophilia were 57% less likely to die from ischaemic heart disease than controls. People with haemophilia in Sweden demonstrate higher mortality over time, independent of HIV and viral hepatitis, despite relatively advantageous access to clotting factor concentrates. "
“Summary.  Acquired factor XIII (FXIII) deficiency, arising from an autoantibody against factor XIII, is a rare bleeding disorder. This

autoimmune disorder most commonly occurs in the elderly. Patients who develop such acquired FXIII inhibitors may present with catastrophic bleeding events and are hard to be diagnosed with the normal general coagulation tests. Though the disease is relatively rare, it is known to cause Selleckchem ACP-196 significant mortality. In this article we briefly describe a patient who presented with extensive bleeding and a normal activated partial thromboplastin time and prothrombin time (PT), but had an acquired inhibitor to FXIII; PIK3C2G her primary disease was systemic lupus erythematosus (SLE). Also, we will focus on the clinical features, treatment modalities, fibrin structure and epitope identification for acquired factor XIII inhibitor with a review of the literature. “
“Summary.  Changes in articular cartilage after haemarthrosis

have not been completely elucidated in haemophilic arthropathy. Insights into the pathophysiological mechanisms of blood-induced joint damage mainly derived from histological, inflammatory and biochemical investigations. A structure–function relationship is another reasonable way to determine the joint overall health status. Cartilage, a viscoelastic connective tissue, is at least a biphasic material that should also work under minimal friction. Pendulum friction tester measures the mechanical aspects of joint lubrication and quantifies the biotribological properties of the joint. Indentation test is an in situ method characterizing the biomechanical properties of the cartilage. Gross, biotribological and biomechanical properties were determined in a rabbit model of experimental haemarthrosis. A sample of 1 mL of fresh autologous blood was injected in the left knee of rabbit’s joint twice weekly for four consecutive weeks. The right knee and animals in the control group were left untreated. After 8 days, joint perimeter, biotribological and biomechanical tests were performed. In a consistent manner, all data showed detrimental effects of the blood on the overall cartilage function under loading.

The hazard ratio for all-cause mortality compared with controls was 2.2, 95% CI: [1.8; 2.7], P < 0.001 for the entire group DNA Damage inhibitor of patients and 1.7, 95% CI: [1.3; 2.2], P < 0.001 when patients with HIV and/or viral hepatitis were excluded. The corresponding figures for the severe haemophilia subgroup were 6.6, 95% CI: [4.5; 10.0], P < 0.001

and 8.2, 95% CI [3.2; 20.8], P < 0.001 respectively. The most common causes of death were related to malignancies and the haemostatic defect. People with haemophilia were 57% less likely to die from ischaemic heart disease than controls. People with haemophilia in Sweden demonstrate higher mortality over time, independent of HIV and viral hepatitis, despite relatively advantageous access to clotting factor concentrates. "
“Summary.  Acquired factor XIII (FXIII) deficiency, arising from an autoantibody against factor XIII, is a rare bleeding disorder. This

autoimmune disorder most commonly occurs in the elderly. Patients who develop such acquired FXIII inhibitors may present with catastrophic bleeding events and are hard to be diagnosed with the normal general coagulation tests. Though the disease is relatively rare, it is known to cause selleck chemicals significant mortality. In this article we briefly describe a patient who presented with extensive bleeding and a normal activated partial thromboplastin time and prothrombin time (PT), but had an acquired inhibitor to FXIII; Epothilone B (EPO906, Patupilone) her primary disease was systemic lupus erythematosus (SLE). Also, we will focus on the clinical features, treatment modalities, fibrin structure and epitope identification for acquired factor XIII inhibitor with a review of the literature. “
“Summary.  Changes in articular cartilage after haemarthrosis

have not been completely elucidated in haemophilic arthropathy. Insights into the pathophysiological mechanisms of blood-induced joint damage mainly derived from histological, inflammatory and biochemical investigations. A structure–function relationship is another reasonable way to determine the joint overall health status. Cartilage, a viscoelastic connective tissue, is at least a biphasic material that should also work under minimal friction. Pendulum friction tester measures the mechanical aspects of joint lubrication and quantifies the biotribological properties of the joint. Indentation test is an in situ method characterizing the biomechanical properties of the cartilage. Gross, biotribological and biomechanical properties were determined in a rabbit model of experimental haemarthrosis. A sample of 1 mL of fresh autologous blood was injected in the left knee of rabbit’s joint twice weekly for four consecutive weeks. The right knee and animals in the control group were left untreated. After 8 days, joint perimeter, biotribological and biomechanical tests were performed. In a consistent manner, all data showed detrimental effects of the blood on the overall cartilage function under loading.

Bid-deficient hepatocytes manifested delayed and reduced serum-stimulated proliferation, which was corrected Lenvatinib by ionomycin or reconstitution of Bid, particularly an ER-targeted Bid. Finally, B cell lymphoma

2–associated X protein (Bax) could also be found in the ER-enriched membranes, and Bax deficiency caused the same proliferation defect. However, Bid/Bax double deletion in hepatocytes did not further augment the defect, which suggested that Bid and Bax worked by the same regulatory mechanism in [Ca2+]ER control. Conclusion: Bid regulates hepatocyte proliferation by positively affecting [Ca2+]ER homeostasis, and this could be important for liver regeneration and carcinogenesis. (HEPATOLOGY 2010) Hepatocytes are highly differentiated cells, GSK126 datasheet but they retain a remarkable ability to proliferate in response to acute or chronic injury.1, 2 In the best studied rodent model of hepatocyte proliferation in vivo, that is, regeneration after 70% partial hepatectomy, the liver returns to its original size within 1 week after the resection. Massive hepatocyte proliferation can be documented within 48 hours in a nearly synchronous fashion. A number of factors are responsible for this

proliferation burst, including hepatocyte growth factor (HGF), epidermal growth factor (EGF), and other growth-promoting agents.1, 2 An important effector of the growth signaling seems to be calcium, which is required for quiescent hepatocytes to enter the cell cycle.3, 4 At the protein level, the transition of the resting hepatocyte into the proliferating state (G0-G1 transition) is characterized by increased cyclin D1 expression.5, 6 Cyclin D1 expression is critically regulated by extracellular stimuli that control hepatocyte proliferation during liver regeneration and in culture.7 There are multiple regulatory mechanisms at each of these steps that affect hepatocyte proliferation, not all of which have been characterized,

particularly at the level of calcium signaling. The B cell lymphoma 2 (Bcl-2) family proteins are best characterized for their regulation of apoptosis by targeting from the mitochondria.8 This family can be divided into two groups: the antiapoptotic members, such as Bcl-2 and B cell lymphoma extra long (Bcl-xL), and the proapoptotic members, such as BH3-interacting domain death agonist (Bid) and B cell lymphoma 2–associated X protein (Bax). Intriguingly, in addition to their function in apoptosis regulation, some members of this family have been found to also affect cell proliferation. Lymphocytes from Bcl-2 transgenic mice exhibited delayed entry into the S phase after mitogen stimulation, whereas those from Bcl-2–deficient mice had accelerated cell cycle entry.