Angiotensinogen and angiotensin-I converting enzyme gene polymorphisms and the risk of coronary artery disease in Chinese

We investigated extracts of timothy grass pollen from four seasons (1989, 1990, 1991, and 1994) by protein content, SDS-PAGE, immunoblot, RAST, RAST inhibition, and crossed immunoelectrophoresis. Extract of the pollen from 1991 showed the lowest yield in quantitative assays. SDS-PAGE, crossed immunoelectrophoresis, RAST, and RAST inhibition expressed approximately comparable patterns for all extracts except that from 1991. Obviously, the quality of grass pollens, as shown for some ragweed (Ambrosia elatior) pollens depend on year of collection. Our findings are partially in agreement with some earlier examinations of the quality of timothy pollen from different pollen seasons.     

The role of individual cysteine residues in the processing, structure, and function of human macrophage colony-stimulating factor

The ontogeny of the hematopoietic system in mammalian embryos occurs during the yolk sac (YS) and the fetal liver (FL) stages. Events leading to the establishment of hematopoiesis in the FL remain obscure. The appearance of colony-forming units-spleen (CFU-S) in the FL is preceded by a gradual increase of CFU-S in the YS and a more rapid increase in the AGM region (area comprising dorsal aorta, gonads, and mesonephros) during day 10 of development (Medvinsky et al, Nature 364:64, 1993). By this time, the AGM CFU-S attain a high frequency equivalent to that found in the adult bone marrow. The analogous area gives rise to adult hematopoiesis in amphibians and probably in birds. We present here a more complete picture of CFU-S development during transition from the pre-liver to liver stage of hematopoiesis. (1) Dissectional analysis of the mouse AGM region shows the presence of CFU-S both around the dorsal aorta and in the uro-genital ridges. (2) The embryonic gut also shows low but distinctive CFU-S activity. This initial intrabody pattern of CFU-S distribution in murine embryogenesis parallels that found for primordial germ cells. (3) The beginning of definitive liver hematopoiesis is accompanied by wide dissemination of CFU-S in the embryonic tissues. (4) Comparison of spleen colonies arising from the AGM and YS has shown morphologic differences. In contrast to simple erythroid constitution of the YS colonies, a broader variety of cells are found within the AGM-derived colonies that are similar to those derived from 11-day FL. These data suggest a lineage relationship for hematopoietic progenitors between the AGM region and the FL.     

Alterations of local cerebral blood flow, phorbol 12,13-dibutyrate binding activity, and histological damage during acute focal ischaemia in rat brain. A pathophysiology of acute focal ischaemia: Part 1

The alterations of the local cerebral blood flow (LCBF), 3H-phorbol 12,13-dibutyrate (PDBu) binding activity were measured, and histological findings were also examined during the closed time course (0, 1, 3, 5, 7 hour) after middle cerebral artery occlusion (MCAO) in rat brain to assess the complex pathophysiology of acute focal ischaemia. From 1 to 3 hours after the start of MCAO, significant (p < 0.01) hyperreactivity of the second messenger system involving PDBu binding may be present, despite low perfusion of LCBF, and severe damage in the striatum whereas sparing almost completely the cortex on histological examination. At 5 hours, the PDBu binding activity increased slightly but not significantly but is reduced markedly at 7 hours after MCAO compared with the control group. The measurement of PDBu binding activity, additionally to measuring the LCBF and observation of the histological change might be a useful indicator in determining the threshold and duration of ischaemia which cause functionally irreversible cell damage in the brain.     

False-positive 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography studies for evaluation of focal pulmonary abnormalities

Positron emission tomography (PET) with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) can demonstrate the glucose metabolism characteristics of a lesion, which may be helpful in differentiating between benign and malignant focal pulmonary lesions. Malignant cells demonstrate higher glucose metabolic activity than benign lesions. However, some inflammatory processes also show significant FDG uptake. We present two cases where high FDG uptake was found in inflammatory lesions in the lungs. The first case was that of a 38-year-old woman with chronic cough for more than 20 years. FDG PET revealed a hypermetabolic lesion with a lesion-to-background ratio of 8.0 at the posterior aspect of the right middle lung. She underwent thoracotomy and tumor resection, and was diagnosed with cryptococcosis. The second case was that of a 72-year-old woman who had pulmonary tuberculosis previously with cavitation in the left lower lobe. She suffered from fever, chills and severe hemoptysis for several days before this admission. FDG PET revealed a hypermetabolic ring at the periphery of the cavity. The lesion-to-background ratio was 7.8. Echo-guided biopsy showed no evidence of malignancy. She was treated with antibiotics and the symptoms subsided gradually. Lung abscess complicating a pre-existing cavity was diagnosed. These two cases substantiate that positive FDG PET results should be interpreted with caution in differentiating benign from malignant pulmonary abnormalities, especially in regions with a high prevalence of granulomatous lesions.     

Construction of vectors expressing bioactive heterodimeric and single-chain murine interleukin-12 for gene therapy

OBJECTIVE: We examined the prevalence, correlates, and predictive value of an abbreviated somatization index, based on specific symptom thresholds, in primary care patients using services at a university-affiliated clinic. METHOD: We interviewed 1456 patients with a survey instrument that included the Composite International Diagnostic Interview (CIDI) to elicit symptoms and diagnoses of several psychiatric disorders as well as demographic information and a measure of disability. Statistical analyses examined the relationship of abridged somatization with physical functioning and various demographic and diagnostic factors. RESULTS: About one fifth of this primary care sample met the abridged somatization criteria. "Somatizers," defined according to these criteria, had significantly higher levels of psychiatric comorbidity and disability than "nonsomatizers". Analyses taking into account the number and type of organ/body systems represented by the unexplained symptoms showed that this dimension adds specificity to the prediction of outcomes. Thus, regardless of the total number of medically unexplained symptoms, abridged somatization with unexplained symptoms attributable to four or more organ/body systems showed the strongest association with disability and psychopathology. CONCLUSIONS: Abridged Somatization is a frequent syndrome in primary care that is strongly associated with psychopathology and physical disability. Our research also yielded a new series of abridged somatization subtypes (eg, "discrete" vs. "comorbid" and "simple" vs. "polymorphous") that may effectively separate among various psychopathologies, and may become useful tools for future research with somatizing patients.     

Suramin is an active site-directed, reversible, and tight-binding inhibitor of protein-tyrosine phosphatases

The effect of suramin, a well known antitrypanosomal drug and a novel experimental agent for the treatment of several cancers, on protein-tyrosine phosphatases (PTPases) has been examined. Suramin is a reversible and competitive PTPase inhibitor with Kis values in the low microM range, whereas the Kis for the dual specificity phosphatase VHR is at least 10-fold higher. Although suramin can also inhibit the activity of the potato acid phosphatase at a slightly higher concentration, it is 2-3 orders of magnitude less effective against the protein Ser/Thr phosphatase 1alpha and the bovine intestinal alkaline phosphatase. Suramin binds to the active site of PTPases with a binding stoichiometry of 1:1. Furthermore, when suramin is bound to the active site of PTPases, its fluorescence is enhanced approximately by 10-fold. This property has allowed the determination of the binding affinity of suramin for PTPases and several catalytically impaired mutant PTPases by fluorescence titration techniques. Thus, the active site Cys to Ser mutants bind suramin with similar affinity as the wild type, while the active site Arg to Ala mutant exhibits a 20-fold reduced affinity toward suramin. Interestingly, the general acid deficient Asp to Ala mutant PTPases display an enhanced affinity toward suramin, which is in accord with their use as improved "substrate-trapping" agents. That suramin is a high affinity PTPase inhibitor is consistent with the observation that suramin treatment of cancer cell lines leads to an increase in tyrosine phosphorylation of several cellular proteins. Given the pleiotropic effects of suramin on many enzyme systems and growth factor-receptor interactions, the exact in vivo actions of suramin require further detailed structure-activity investigation of suramin and its structural analogs.     

Structure of hydrated oligonucleotides studied by in situ scanning tunneling microscopy

We have used the scanning tunneling microscope (STM) to image several synthetic oligonucleotides adsorbed onto a positively charged Au(111) electrode. The molecules were deposited and imaged in aqueous electrolyte under potential control, a procedure that eliminated the problem of the substrate artifacts that had limited some previous STM studies. Experiments were carried out with two types of single-stranded molecules (11 and 20 bases long) and three types of double-stranded molecules (20 and 61 base pairs and 31 bases with 25 bases paired and 6-base "sticky" ends). The molecules lie along symmetry directions on the reconstructed (23 x square root of 3) gold surface, and length measurements indicate that they adopt simple base-stacked structures. The base stacking distances are, within experimental uncertainty, equal to the 0.33 nm measured for polymeric aggregates of stacked purines by direct imaging in identical conditions. The images show features consistent with helical structures. Double helices have a major-groove periodicity that is consistent with a 36 degrees twist. The single helices appear to be more tightly twisted. A simple tunneling model of STM contrast generates good agreement between measured and calculated images.