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Biomedical subjects

A Bloch

Publications and source records attributed to A Bloch.

At least 19 recordsLinked to original sources
PubMed1998

Tumor suppressor proteins as regulators of cell differentiation.

The products of the tumor suppressor genes are considered to function as specific inhibitors of tumor cell growth. In this communication, we present evidence to show that these proteins inhibit tumor cell proliferation by participating in the activation of tumor cell differentiation. The ML-1 human myeloblastic leukemia cells used in this study proliferate when treated with insulin-like growth factor I and transferrin but differentiate to monocytes when exposed to tumor necrosis factor alpha or transforming growth factor beta1, or to macrophage-like cells when treated with both these cytokines. Initiation of proliferation but not of differentiation was followed by a 20- to 25-fold increase in the nuclear level of the DNA polymerase-associated processivity factor PCNA and of the proliferation-specific transcription factor E2F1. In contrast, induction of differentiation but not of proliferation was followed by a 25- to 30-fold increase in the nuclear level of the tumor suppressor proteins p53 (wild type), pRb, and p130/Rb2 and of the p53-dependent cyclin kinase inhibitor p21/Cip1. p53 and p21/Cip1, respectively, inhibit the expression and activation of PCNA, whereas p130 and pRb, respectively, inhibit the expression and activation of E2F1. As a result, G1-S-associated DNA and mRNA synthesis is inhibited, growth uncoupled from differentiation, and maturation enabled to proceed. Where this function of the tumor suppressor proteins is impaired, the capacity for differentiation is lost, which leads to the sustained proliferation that is characteristic of the cancer cell.

Carrier Proteins↗
PubMed1998

[Clinical value of measuring systolic arterial blood pressure post-exercise for evaluation and diagnosis of coronary disease: comparative study between women and men].

It has been demonstrated that the ratio of the systolic blood pressure post-exercise to that at peak exercise (rSBP) is a criterion for diagnosis and severity of coronary artery disease (CAD) in men. No such demonstration has been attempted in women. We have compared SBP to classical signs of ischemia, such as ST segment depression and angina pectoris, in a group of 788 ambulatory patients of whom 357 were women. All underwent a bicycle ergometric test and a coronary angiogram. The prevalence of CAD at angiography was the same for both genders (women 43.5% and men 47%) with no significant difference in the number of vessels diseased. In patients with CAD, the rSBP was significantly more elevated than in others, at 1 minute (p < 0.01) and even more so at 3 minutes (p < 0.001) post-exercise, with no gender difference. The most discriminating value of rSBP at 3 minutes post-exercise for diagnosis of CAD was situated at 0.91 for sensitivity and specificity (receiver operating characteristic curve analysis). In the whole group sensitivity of rSBP is lower, while the specificity is greater than classical criteria of ischemia. The sensitivity of rSBP is poor for the diagnosis of single vessel disease, but of equal value compared to ST segment depression in the presence of multivessel disease, with no gender difference. The specificity of rSBP is higher than ST segment depression in women (p < 0.001) compared to men (p < 0.05). rSBP has a positive correlation with the number of coronary vessels diseased but not with the extent of ST segment depression. Our study demonstrates that rSBP at 3 minutes post-exercise is a less good diagnostic sign than the classical criteria of myocardial ischemia. However, rSBP has good specificity, particularly in women, thus reducing false positive tests related to ST segment depression. rSBP is also a marker of the severity of coronary artery disease.

Aged↗
PubMed1998

[Symptomatic coronary disease associated with mitral insufficiency: surgical strategy].

In recent years coronary artery bypass grafting (CABG) has been extended to include patients with very low left ventricular ejection fractions (LVEF), also frequently with co-existing mild to moderate mitral valve regurgitation (MR). The question is, should MR be corrected simultaneously with a myocardial revascularization or not? Between January 1990 and December 1996, 82 patients with preoperative LVEF < or = 0.25 and echocardiographic evidence of co-existing MR without chordal or papillary muscle rupture (Grade I-28%, II-35%, III-32% and IV-5%) underwent primary CABG. None of them underwent simultaneous mitral valve surgery. The mean preoperative LVEF was 0.17 +/- 0.04 (0.10-0.25), mean PAP 43.8 +/- 15.9 mmHg. An average of 4.4 +/- 1.5 grafts/ patient were placed. The overall mortality was 3.7% (3/82). Transient postoperative low cardiac output syndrome occurred in 24 patients (29%). Thirty-two patients (39%) had no postoperative complications at all. Seventy-nine hospital survivors were followed up over a period of 18 months (6-48 months) on average. There was one death (8 months post-operatively) and 2 graft occlusions, not requiring redo surgery. At the end of follow up echocardiography showed that 45 patients had no MR at all and 28 patients had MR-Grade I, a total of 73 patients (94%). Five patients had Grade II-III MR, none of them requiring mitral valve surgery. All patients improved their NYHA functional class, from 3.5 +/- 0.7 to 1.8 +/- 0.5 and the LVEF from 0.17 +/- 0.04 to 0.46 +/- 0.08, p < 0.001. Moderate to severe co-existing MR (Grade II-IV) seems to normalize after the myocardial revascularization and should therefore not be surgically corrected at the primary operation, if there are no echocardiographic evidence of chordal or papillary muscle rupture. Peroperative control echocardiography is recommended.

Adult↗
PubMed1997

Differential expression of proteins regulating cell cycle progression in growth vs. differentiation.

The level of various G1 cyclins and cyclin-dependent kinases (cdks) present in the nuclei of synchronized ML-1 human myeloblastic leukemia cells was determined as a function of time after initiation of cell growth with insulin-like growth factor-1 (IGF-1) and transferrin (Tf), and following induction of differentiation with transforming growth factor-beta1 (TGF-beta1). Cyclin E and cdk2 were expressed at relatively high levels in the nuclei of proliferation-stimulated cells, whereas cyclin D1 and cdk5 were expressed at comparably high levels in the nuclei of differentiation-induced cells. In the nuclear extracts from proliferation-stimulated cells, cyclin E complexed specifically with cdk2, whereas in nuclear extracts from differentiation-induced cells, cyclin D1 bound specifically to cdk5. Increased cyclin E/cdk2 expression was accompanied by increased DNA synthesis, whereas increased cyclin D1/cdk5 levels correlated with decreased DNA synthesis. In both growth- and differentiation-induced cells, cyclin D2 expression preceded the expression of cyclin D3, and a significantly larger amount of these cyclins was present in differentiation- as compared to proliferation-induced cells. In contrast, cdk4 and cdk6 were present at similar levels in the nuclear extracts from both growth- and differentiation-induced cells. These data show that, in ML-1 cells, the proliferation-associated progression from G1 to S, as well as the differentiation-associated transit from G1 to maturation is accompanied by the expression of specific cyclin/cdk pairs, comprising cdk2/cyclin E in growth and cdk5/cyclin D1 in differentiation.

CDC2-CDC28 Kinases↗
PubMed1997

[Ambulatory blood pressure measurement: clinical significance and prognostic evaluation of nocturnal arterial hypertension].

With the aim of determining the clinical and prognostic value of the onset of a cardiac and/or cerebral event and nocturnal hypertension, we retrospectively investigated 291 patients with essential hypertension by noninvasive ambulatory 24-hour blood pressure measurement. The patients were followed for 1809 +/- 107 days. During the follow-up period 21 patients suffered a nonfatal cardiovascular event. The patients experiencing this type of event showed a higher nocturnal systolic blood pressure and a smaller diurnal/nocturnal difference for systolic blood pressure values at diurnal blood pressure values comparable to those without a cardiovascular event. Patients with nocturnal hypertension, with or without inversion of the circadian rhythm, were statistically more likely to suffer a cardiovascular event than patients with a normal circadian profile. Our investigation revealed a certain prognostic value for nocturnal hypertension in the evaluation of essential hypertension, the prognosis being more favourable in hypertensive patients with a normal circadian profile.

Adult↗
PubMed1997

[Prognostic significance of exercise-induced hypertension].

The significance of exercise-induced hypertensive blood pressure values is poorly known. The present study has looked for a correlation between hypertensive systolic blood pressure values on exercise in a normotensive population and later development of hypertension at rest. After elimination of patients with hypertension at rest and of patients lost to the follow-up, this study includes 74 normotensive subjects who had developed exertional hypertension (blood pressure superior to 220/95 mmHg) during exercise testing. At the end of an average follow-up of six years, 40.5% of these patients are showing hypertension at rest. Thus hypertensive blood pressure values on exercise in a normotensive subject is an important finding. It should lead to an adaptation of diet and life style and to regular blood pressure controls.

Aged↗
PubMed1997

[Is white-coat hypertension a disease?].

White-coat hypertension can be defined as a hypertensive reaction in the physician's office in a usually normotensive individual. Several studies have shown that white-coat hypertension may be associated to slight metabolic or echocardiographic abnormalities, putting these individuals between normal subjects and true hypertensives; however, long-term evolution of white-coat hypertensives remains poorly known. The present study tries to solve this question. A retrospective study was performed on 63 individuals with office hypertension but normal ambulatory blood pressure monitoring. After a mean follow-up of 5.4 years, more than half of these subjects have become permanent hypertensives, the majority of them being at this time under hypotensive treatment. White-coat hypertension is probably not a disease but a factor predictive of later permanent hypertension; therefore, such individuals should be submitted to life style changes and to regular blood pressure controls.

Antihypertensive Agents↗
PubMed1997

Indexes of food and nutrient intakes as predictors of serum concentrations of nutrients: the problem of inadequate discriminant validity. The Polyp Prevention Trial Study Group.

Nutrient indexes derived from food-frequency questionnaires have generally been regarded as acceptably valid for epidemiologic purposes. Evaluations of these indexes, however, have considered only their convergent validity. We suggest that discriminant validity, or the ability to distinguish among exposures to different nutrients, is also important. Using baseline data from a large clinical trial, we tested the discriminant validity of indexes of intake of vitamin E, alpha-carotene, and beta-carotene. Our results suggest that the vitamin E index possesses neither convergent not discriminant validity, the alpha-carotene index adequate convergent and discriminant validity, and the beta-carotene index adequate convergent but no discriminant validity.

Biomarkers↗
PubMed1996

[Surgical correction of the ventricular geometry in post-infarction left ventricular aneurysms].

Left ventricular aneurysm (LVA) following myocardial infarction carry a high morbidity and mortality, which may be reduced by appropriate surgical treatment. The Jatene correction is an attractive technique for aneurysm repair. We have employed a modified Jatene correction in 72 patients between July 1986 and May 1995. There were 57 men and 15 women, mean age 61.6 +/- 8.2 years old. Fifteen patients (21%) presented with malignant recurrent ventricular arrhythmias. Fourteen patients had emergency operations and 3 were redo coronary artery bypass grafts. Fifty-eight patients (83%) were in NYHA class III and IV. Fifty-two patients had 3-vessel disease. Preoperative left ventricular ejection fraction (LVEF) was 30.4 +/- 12.2% (10-59%) and left ventricular end-diastolic pressure was 26.2 +/- 10.1 mmHg (12-41 mmHg). The overall perioperative mortality was 11.1%, one patient had a peroperative myocardial infarction. Immediately postoperatively, 17 patients had low cardiac output, requiring intraaortic balloon pump in eight cases. There were no bleeding problems and 30 patients (42%) had no postoperative complications whatsoever. The average hospital stay was 10.2 days. Left ventricular cavity size, measured (echocardiography) showed significant reduction 1 week postoperatively, which was unchanged after 1 month. The left ventricular ejection fraction was significantly increased 1 month postoperatively. After follow-up, on average 20 months, there was significant improvement in mean NYHA class. The modified Jatene correction of left ventricular aneurysm is simple, carries acceptable mortality and low morbidity and significantly improves left ventricular function.

Aged↗
PubMed1995

Activation of casein kinase II in ML-1 human myeloblastic leukemia cells requires IGF-1 and transferrin.

Casein kinase II (CK II), a key enzyme involved in the regulation of cell growth, has been variously reported to be activated by diverse mitogens, including insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF). Activation of the enzyme is generally carried out in the presence of serum, and we examined the question whether serum components participate in the activation process. We demonstrated previously that ML-1 cells require IGF-1 plus transferrin (TF) for growth and transforming growth factor beta or tumor necrosis factor alpha plus TF for differentiation. We now found that CK II is activated only when the cells are exposed to both IGF-1 and TF or when TF is replaced in this combination with relatively high levels of iron salts. Induction of differentiation with TGF-beta and TF did not result in CK II activation. These results show that CK II activation in ML-1 cells requires the application of both components of the growth signal, IGF-1 and TF, demonstrating that the growth factor alone is incapable of enhancing the activity of the enzyme.

Amino Acid Sequence↗
PubMed1995

Regulation of c-myb expression in ML-1 human myeloblastic leukemia cells by c-ets-1 protein.

C-myb and c-ets-1 have variously been demonstrated to function as protooncogenes. Using a human leukemic cell line, ML-1, we have examined the mechanism by which these genes participate in establishing the sustained proliferation mode that is characteristic of the transformed cell. In the absence of serum, ML-1 cells were found to require IGF-1 and transferrin (TF) for growth and TGF-beta or TNF-alpha plus TF for differentiation. Upon administration of the growth factors, c-myb expression increased within 60 min, whereas after addition of the differentiation factors c-myb expression ceased completely within 3 hr. A correlation was found to exist between the level of c-ets-1 protein in the cells, the extent to which that protein is bound to intron I of the myb gene and the amount of c-myb mRNA that is expressed. Upon administration of growth factors, a sizable increase in the intracellular, and particularly, in the intranuclear level of c-ets-1 protein was observed, whereas a pronounced decrease in the level of this protein occurred after exposure to the differentiation factors. These data demonstrated that the level at which an oncogene-specified transcription factor is expressed can affect the expression of other target oncogenes involved in the regulation of cell proliferation. Stimulated expression of such transcription factor can then lead to the continuous proliferation cycle characteristic of the cancer cell.

Blotting, Western↗
PubMed1995

Is reoperative coronary artery bypass grafting in patients with poor left ventricular ejection fractions < or = 25% worthwhile?

AIM: This study aimed to investigate whether patients with very low left ventricular ejection fractions (LVEF) should be accepted for reoperative coronary artery bypass grafting (CABG). STUDY POPULATION: Between January 1990 and December 1993, 1681 patients underwent primary CABG and 308 (15.5%) reoperative CABG. One hundred and eight patients (5.4%) had an LVEF < or = 25%, 91 patients for primary CAGB (group I) and 17 for CABG (group II). The mean age of the patients was 62 years. Sex distribution and preoperative risk factors did not differ. Urgent operations were more frequently necessary in group II (P < 0.01). Mitral regurgitation was present in 49% of the group I patients and 18% of the group II patients (P < 0.05). Pulmonary artery hypertension was observed in 24% of group I patients, but in only 6% in group II patients. The mean LVEF was 21% and left ventricular end-diastolic pressure 18 mmHg, without between-group differences. All patients had significant two- or three-vessel disease (stenosis > or = 70%). An average of 4.5 grafts per patient were performed. Mitral valve surgery was not performed in any of the patients. RESULTS: The postoperative mortality was significantly higher in reoperative CABG patients (group II; 23.5%) than in group I patients (12.1%; P < 0.05), whereas the incidence of non-fatal myocardial infarction did not differ. The incidence of postoperative complications did not differ between the groups, except for transient renal failure, more frequently encountered in group II (P < 0.05). After an average follow-up of 18 months, the New York Heart Association (NYHA) class and the LVEF were significantly improved in both groups (NYHA class from 3.5 to 1.8 and LVEF from 21% to 45%; P < 0.001). The mitral regurgitation had improved or completely disappeared at the end of follow-up in all patients in both groups. CONCLUSIONS: Our results suggest that patients with left ventricular ejection fraction < or = 25%, angina and significant two- or three-vessel coronary artery disease should not categorically be refused for reoperative CABG. Careful patient selection is necessary because of an increased operative risk.

Case-Control Studies↗
PubMed1995

Jatene correction of the ventricular geometry in postinfarction left ventricular aneurysm. Results of 62 operations.

Jatene correction of left ventricular aneurysm was performed on 62 patients (including 11 emergency operations) with mean age 60 years, 80% of them in NYHA class 3-4, with mean left ventricular ejection fraction c. 30%and mean left ventricular end-diastolic pressure c. 24 mm. Concomitant bypass grafting was performed in 58 cases (mean grafts per patient 3.7). Perioperative mortality was 12.9%. One patient had peroperative myocardial infarction. Postoperatively 13 patients had low cardiac output, requiring intra-aortic balloon pump in seven cases. There were no bleeding problems and 28 patients (45%) had no postoperative complications. The average hospital stay was 10.2 days. Left ventricular cavity size (echocardiography) showed significant reduction 1 week postoperatively, which was unchanged after 1 month. The left ventricular ejection fraction was significantly increased 1 month postoperatively. After follow-up averaging 15 months there was significant improvement in mean NYHA class. One patient underwent heart transplantation and died, but there were no other late deaths or cardiac-related complications. Jatene correction of left ventricular aneurysm is simple, carries acceptable mortality and low morbidity and significantly improves left ventricular function.

Echocardiography↗
PubMed1995

Mitral regurgitation in patients with coronary artery disease and low left ventricular ejection fractions. How should it be treated?

In recent years, coronary artery bypass grafting has been extended to include patients with very low left ventricular ejection fractions. Should concomitant mitral valve regurgitation be corrected simultaneously? Between January 1990 and July 1994, 43 patients with preoperative left ventricular ejection fractions < or = 25% and echocardiographic evidence of concomitant mitral valve regurgitation (grade I, 18 patients; II, 19 patients; and III, 6 patients) underwent primary coronary artery bypass grafting. None of these patients underwent simultaneous mitral valve surgery. Twenty-four patients (56%) had pulmonary artery pressures > or = 40 mmHg (pulmonary hypertension). The mean preoperative left ventricular ejection fraction was 18.7% +/- 4.4% (range, 10% to 25%), and the mean pulmonary artery pressure was 45.6 +/- 15.8 mmHg. The average of number of grafts per patient was 4.5 +/- 1.5. Five patients underwent simultaneous repair of a left ventricular aneurysm. The hospital mortality rate was 4.7% (2/43). Transient low cardiac output occurred postoperatively in 13 patients (30%). Sixteen patients (37%) had no postoperative complications. The average follow-up of the 41 hospital survivors was 6 months (range, 1 to 32 months). One patient died 8 months after surgery for an overall mortality rate of 7%. Another 2 patients had graft occlusions that did not require reoperation. In the 40 surviving patients, follow-up echocardiography revealed that 37 patients (93%) had either no mitral valve regurgitation or only very mild mitral valve regurgitation (grade I). Three patients had grade II mitral valve regurgitation, but none required mitral valve surgery. The New York Heart Association functional class improved significantly in all hospital survivors (from 3.4 +/- 0.6 to 1.7 +/- 0.7; p > 0.001), and left ventricular ejection fractions rose from 19.0% +/- 4.6% to 42.0% +/- 8.3%. Coronary artery bypass grafting is possible in patients with very low left ventricular ejection fractions who present with 2- or 3-vessel disease, significant coronary artery stenoses (less than or equal 70%), and angina. The mortality rate is acceptable and morbidity is low. If there is no rupture of papillary muscle or chordae, concomitant ischemic mitral regurgitation (grades I through III) seems to return to normal after coronary artery bypass grafting and, therefore, does not need to be corrected surgically during the primary operation.

Adult↗