Molecular biology of phospholipid transfer protein

Lipid transfer proteins play an essential role in the intravascular dynamics of lipids among lipoproteins and between lipoproteins and cell membranes. Phospholipid transfer protein has been known for over a decade but, unlike cholesteryl ester transfer protein, has been investigated relatively little with regard to its physiological importance. The recent determination of the phospholipid transfer protein complementary DNA sequence as well as the further characterization of its gene structure will direct future studies toward the understanding of its structure-function correlations, physiological regulation, and clinical assessment at the molecular level. As a member of the lipid-transfer lipopolysaccharide-binding protein gene family, phospholipid transfer protein will attract investigators to studying its possible involvement in lipopolysaccharide or endotoxin interactions in addition to its phospholipid transfer activity.     

T2-weighted breath-hold MRI of the liver at 1.0 T: comparison of turbo spin-echo and HASTE sequences with and without fat suppression

To compare the clinical usefulness of T2-weighted breath-hold sequences for imaging the liver, 33 patients with 97 focal hepatic lesions were studied with a 1.0-T scanner by using T2-weighted breath-hold turbo spin-echo (SE) sequences and T2-weighted breath-hold half-Fourier single-shot turbo SE (HASTE) sequences with and without fat suppression. Images were quantitatively analyzed for liver signal-to-noise ratio (SNR) and lesion-to-liver contrast-to-noise ratios (CNR). Qualitative analysis was performed for lesion conspicuity, motion artifacts, and anatomic sharpness of extrahepatic structures. Breath-hold turbo SE imaging with fat suppression showed the highest CNR for cystic lesions and the best lesion conspicuity for cystic and solid lesions among the four sequences. For solid lesions, there was no significant difference of lesion-to-liver CNR between them. HASTE sequence was superior to turbo SE sequences in terms of motion artifacts; however, the usefulness for evaluating focal hepatic lesions was limited compared with turbo SE sequence with fat suppression. Addition of fat suppression was not helpful for HASTE imaging because of decreased lesion conspicuity and extrahepatic details without the advantage of reducing motion artifacts. This study suggests that turbo SE sequence with fat suppression is most useful for breath-hold T2-weighted liver imaging at 1.0 T. Addition of imaging without fat suppression can be considered for evaluating extrahepatic structures. HASTE sequence may have a role for imaging uncooperative patients due to absence of motion artifacts.     

The prognostic significance of sialyl-Tn antigen in women treated with breast carcinoma treated with adjuvant chemotherapy

BACKGROUND: Sialyl-Tn (STn) represents an aberrantly glycosylated mucin epitope that is expressed in breast carcinoma and other adenocarcinomas and is an important factor in the development of novel immunotherapeutic approaches. The primary aim of the current study was to investigate the influence of STn expression on the prognoses of patients with breast carcinoma. METHODS: A cohort of 207 women diagnosed with invasive breast carcinoma who were treated with anthracycline-containing adjuvant chemotherapy and were enrolled in a randomized clinical trial were studied. Expression of STn was determined by an immunohistochemical procedure in which the B72.3 monoclonal antibody was used. Kaplan-Meier and Cox proportional regression survival analyses were used to compare low STn and high STn patients. RESULTS: Forty-eight (23%) of the 207 specimens demonstrated high STn staining (>25% cells were immunoreactive). During a median follow-up of 5 years, high STn patients had worse disease free survival than low STn patients (55% vs. 74%, respectively; P = 0.03). High STn expression was significantly associated with age (P = 0.04) but not with other conventional prognostic markers. In multivariate analysis using the Cox regression model, high STn emerged as an independent prognostic indicator for disease free survival (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.09-3.73) and for overall survival (HR, 2.16; 95% CI, 0.95-4.92). CONCLUSIONS: The results of this study suggest that STn may be a valuable marker for identifying women at high risk of developing recurrent breast carcinoma who may be candidates for trials investigating new therapies in combination with standard adjuvant therapy.     

The Tel Aviv Stroke Registry. 3600 consecutive patients

BACKGROUND AND PURPOSE: We undertook to estimate the frequency of various risk factors and the type and severity of stroke in different ethnic groups documented in a large hospital-based stroke registry. Tel Aviv is a metropolis with about 400000 inhabitants and about 600000 daily visitors and workers. The Tel Aviv Medical Center (TAMC) is the only tertiary medical care facility to which all patients with acute stroke are referred. Israel is a country with a heterogeneous population, of which a significant proportion was born abroad. The people differ in their genetic background, as well as in their early environmental conditions, lifelong diet, and other habits. This variety has proved to be a fertile ground for the study of different neurological diseases, including stroke. METHODS: A prospective hospital-based registry using systematic computer coding of data of all consecutive stroke patients admitted to the TAMC has been conducted since May 1988. Different aspects of the amassed data were analyzed statistically. RESULTS: From May 1988 until April 1994, 3600 stroke patients were admitted to the TAMC. The mean age was 73.2 years, and 58.2% were males. Cerebral infarctions were diagnosed in 80.9%, primary intracerebral hemorrhages in 8.0%, and transient ischemic attacks in 11.1%. There were 861 patients (24%) who were admitted with recurrent strokes. Past medical history of hypertension was the major risk factor (occurring in 52.2% of the patients), followed by ischemic heart disease (29.7%), diabetes mellitus (25.2%), smoking (17.0%), atrial fibrillation (14.3%), and hyperlipidemia (8.4%). Ischemic heart disease and atrial fibrillation were more frequent in patients from Europe and America (Ashkenazi group), whereas diabetes mellitus and smoking were more prominent in the other groups. The in-hospital mortality rate was 13.8% and was similar in both ethnic groups. CONCLUSIONS: This registry allows the study of the risk factors, natural history, and clinical manifestations of stroke in different ethnic groups.     

Differential participation of hippocampal formation in cocaine-induced cortical electroencephalographic desynchronization and penile erection in the rat

Rts1 RepA and P1 RepA are trans-acting proteins essential for initiation of replication of Rts1 and P1 plasmids, respectively. We recently found that P1 RepA bound in vitro to the Rts1 replication origin as strongly as Rts1 RepA and activated the origin in vivo. However, the ori activation was quite inefficient. This study shows that by replacing a small region of P1 RepA with the corresponding region of Rts1 RepA, the efficiency of Rts1 ori activation increased markedly. Interestingly, the same subregion of P1 RepA was found to be important for in vivo activation of the P1 origin. Thus, a region essential for efficient activation of the replication origin was assigned to the P1 RepA molecule as well as to the Rts1 RepA molecule. The region was distinct from a domain necessary for in vitro binding to the origin, although both regions were required for in vivo activation of the respective origin.     

Liver microsomal drug-metabolizing enzyme system: functional components and their properties

The liver microsomal drug-metabolizing enzyme system consists of two protein components, cytochrome P-450 and NADPH-cytochrome c reductase, and a lipid, phosphatidylcholine. Cytochrome P-450 serves as the binding site for oxygen and substrate while the reductase acts as an electron carrier shuttling electrons from NADPH to cytochrome P-450. The phospholipid facilitates the transfer of electrons from NADPH-cytochrome c reductase to cytochrome P-450 but itself is not an electron carrier. Different cytochromes P-450 and P-448 have been purified; the spectral, catalytic, and immunological properties as well as the molecular weight (determined by SDS-gel electrophoresis) of all these hemeproteins differ from one another. The presence of multiple cytochrome P-450s may explain the species, strain, age, tissue, and sex differences as well as the effect of inducers and nutritional status in mammlian drug metabolism.