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Biomedical subjects

L Kapusta

Publications and source records attributed to L Kapusta.

31 records · Page 2Linked to original sources

The prognostic significance of altered cyclin-dependent kinase inhibitors in human cancer.

Progression through the cell cycle is governed by cyclin-dependent kinases (cdks), whose activity is inhibited by the cdk inhibitors. Cyclins, cdks, and cdk inhibitors are frequently deregulated in cancers. This chapter reviews the prognostic significance of alterations in cdk inhibitors. Loss of p27 protein provides independent prognostic information in breast, prostate, colon, and gastric carcinomas, and immunohistochemical (IHC) staining for p27 may eventually become part of routine histopathologic processing of cancers. Loss of IHC staining for p21 may be prognostic in certain cancers but conflicting results are reported in breast cancer. Reports on homozygous deletion of p16 and p15 genes suggest the value of larger, prospective studies with standardized treatment protocols to definitively establish the prognostic utility of p15/p16 deletions in acute leukemias. Larger trials and the development of a consensus on methods for deletion analysis, IHC staining, and tumor scoring will be needed to move these molecular assays from bench to bedside.

Breast Neoplasms↗

Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer.

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for reliable prognostic markers to assist clinicians in making management decisions. Although a variety of factors have been tested, only tumor stage, grade, size, hormone receptor status, and S-phase fraction are used on a routine basis. The cell cycle is governed by a family of cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by phosphorylation. p27Kip1, a cyclin-dependent kinase inhibitor, regulates progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27Kip1 protein levels and/or activity are upregulated by growth inhibitory cytokines including transforming growth factor-beta (TGF-beta) and, thus, provide an important link between extracellular regulators and the cell cycle. Loss of p27Kip1, a negative cell-cycle regulator, may contribute to oncogenesis and tumor progression. However, p27Kip1 mutations in human tumors are extremely rare. We have demonstrated by immunohistochemistry that p27Kip1 protein levels are reduced in primary breast cancers and that this is associated with tumor progression in both in situ and invasive lesions. This was confirmed by western analysis, reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to be regulated posttranscriptionally by in situ hybridization. Furthermore, on multivariate analysis, low p27Kip1 is a predictor of reduced disease-free survival. This simple and reliable immunohistochemical assay may become a routine part of breast cancer evaluation and may influence patient management.

Biomarkers, Tumor↗

Craniofrontonasal dysplasia.

We report on nine patients with craniofrontonasal dysplasia (CFND). Seven classical cases had facial features suggestive of frontonasal dysplasia and coronal craniosynostosis. Extracranial abnormalities such as brittle nails with prominent longitudinal grooves or syndactyly of fingers and toes were observed in individual patients. In two families the father of classical cases showed a milder pattern of abnormalities, consistent with the diagnosis. We present a 2- to 13-year follow-up on our patients. Hypotonia and laxity of joints are common and may necessitate supportive measures. Mild developmental delay was noted in three out of six classical cases studied in detail. Unlike almost all other X-linked disorders, clinical expression in CFND is generally much more severe in females than in males. In contrast to previous reports of this condition, one of our severely affected cases is a male.

Abnormalities, Multiple↗

The agreement between pulmonary and systemic blood flow measurements in babies by dual beam Doppler echocardiography.

Measurement of cardiac output within the great arteries of infants by non-invasive Doppler echocardiographic techniques is limited. This paper describes a simple method, based on dual beam Doppler, that is capable of measuring the pulmonary and systemic blood flows independently of the vessel diameter and beam-blood flow angle. In 27 babies (12 of them were premature born) without intracardial shunts the accuracy of this method in measuring cardiac output was evaluated. The mean difference between pulmonary and systemic blood flow measurements was 0.02 (SD 0.06) 1 min-1. This study demonstrates a good agreement between the pulmonary and systemic blood flow measurements using dual beam Doppler ultrasound in babies.

Aorta↗

The role of DNA flow and image cytometry in the evaluation of body cavity fluids.

In addition to conventional cytomorphologic study, 50 body cavity fluid specimens (benign and malignant) were analyzed by both flow cytometry (FCM) and image cytometry (ICM) in order to evaluate the potential application of these techniques in the diagnosis of malignancy. While 88% of the fluids were similarly classified by FCM and ICM as being either diploid (66%) or nondiploid (22%), with similar DNA index values, nondiploid peaks were identified by ICM alone in 12% of the fluids. Aneuploid populations were present in 92% of the cytologically positive fluids and in 15% of the cytologically negative fluids. All of the latter fluids came from patients who clinically had tumors involving the respective body cavities. These results show that (1) both FCM and ICM are useful adjuvant techniques in the evaluation of body cavity fluid specimens and (2) ICM is superior to FCM in the identification of small aneuploid subpopulations. The identification of aneuploid populations by either method is highly suggestive of malignancy.

Adult↗

Moya-Moya syndrome and primary pulmonary hypertension in childhood.

A child is described with Moya-Moya disease and a primary pulmonary hypertension. This association has never been reported until now. It is attempting to consider a common vascular denominator for both diseases although we were not able to prove this hypothesis.

Cerebral Arteries↗

The usefulness of cross-sectional Doppler flow imaging in the detection of small ventricular septal defects with left-to-right shunt.

Small ventricular septal defects (VSDs) with left to right (L-R) shunt have been difficult to diagnose with conventional ultrasound techniques. Using the cross-sectional Doppler flow imaging system, additional information can be obtained. In a group of 60 patients with a clinical diagnosis of VSD with L-R shunt, the new technique proved valuable, especially in detecting muscular and apical VSDs.

Adolescent↗

[Myocarditis and thrombosis].

Thrombo-embolic events are important complications of myocarditis, associated with a dilated and decreased contracting left ventricle. With echocardiography it is possible to prove the diminished left ventricular function as well as the presence of a thrombus. Early anti-thrombotic therapy is indicated in these cases. This will be demonstrated in a case history.

Echocardiography↗

The effect of epidural analgesia on maternal thermoregulation in labor.

Core and peripheral body temperatures were recorded in 24 parturients in labor with epidural analgesia and in 9 control parturients without analgesia. Shivering occurred in 11 (46%) of the women with epidural analgesia and in one parturient without analgesia. Twelve patients (50%) showed increase in leg and chest temperatures after injection of bupivacaine 0.35% into the epidural space. Lumbar epidural analgesia may produce shivering and temporary temperature changes in the periphery. Core temperature is not significantly altered.

Adult↗