Effectiveness of fetal fibronectin testing compared with digital cervical assessment of women with preterm contractions

The purpose of this study is to determine the effectiveness of fetal fibronectin (FFN) compared to assessment of cervical dilation (CD) in clinical management of women with symptomatic preterm labor (PTL). Pregnant women presenting to Thomas Jefferson University Hospital between May 1, 2001 and November 30, 2002 with symptomatic PTL underwent FFN sampling and had a complete clinical evaluation including a pelvic bimanual examination. Inclusion criteria were singleton pregnancy, gestational age (GA) between 24 (0) and 33 (6) weeks, CD < 3 cm, and intact amniotic membranes. FFN samples were sent out and results were available within 4-12 hours. Clinical management including tocolysis, antenatal steroids, and hospitalization was determined based on digital CD assessment and FFN status. A dilated cervix was defined as CD > 1 cm. Ninety-three patients were included. Spontaneous preterm delivery (SPTD) at < 37 weeks occurred in 20 of 93 (21.5%) patients. Medical therapy use was significantly higher in patients with dilated cervix than in those with a closed cervix (all P values < 0.05). Tocolysis and steroid use in FFN-negative patients and FFN-positive patients were not significantly different. Furthermore, tocolytic use was higher in FFN-negative patients than in women with positive FFN (50% versus 42.1%; P = 0.53). Use of antenatal steroids was similar in patients with CD >/= 1 cm and a positive FFN (54.5% versus 47.4%; P = 0.92). Compared with FFN-negative patients, women with closed cervix were less likely to undergo interventions. In symptomatic PTL patients, CD determined clinical management more than FFN status. Overall, the use of FFN was not effective in decreasing "unnecessary" clinical interventions.     

Studies on passive transfer of anti-dextran and anti-egg albumin reactivity in the rat.

We were unable, passively, to transfer reactivity against dextran to the skin or peritoneal mast cells of non-dextran-reactive rats, by using serum or material eluted at pH 3 from mast cells of spontaneously dextran-reactive rats. When the dextran-reactive donor rats had also been immunized against egg albumin (EA) with pertussis vaccine (inducing IgE anti-EA antibody), passive sensitivity against EA (but not against dextran) could easily be transferred. The results indicated that the anti-dextran reactivity is not due to IgE antibody. Systemic reactions against dextran and EA differed in pattern, supporting the concept that the two substances acted through different mechanisms.     

Trends in dietary fiber intake in Japan over the last century

Summary. Background: Insufficient intake of dietary fiber (DF) is currently a major problem in the overall promotion of health in the general population in Japan. Aim of the study: To analyze the time trends in DF intake, including DF density (total DF intake/1,000 kcal), and the ratio of water-insoluble fiber to water-soluble fiber (IS ratio) in Japan. Methods: The time trend in DF intake in Japan was calculated from data compiled in the Japanese National Nutrition Survey. Results: The mean daily DF intake (total DF intake) in 1952 was 20.5 g/day, which rapidly declined to about 70 % of the 1952 level in 1970, after which there was little change to 1998. DF density in 1952 was 9.7 g/1000 kcal, which declined by about 30 % in 1970, and remained at about the same level to 1998. The IS ratio has remained stable over this period. Whereas total DF intake and DF density in Japan are similar to those in Western countries, the IS ratios are higher in Japan. Therefore, the higher incidence of, and mortality from, colon diverticulosis, coronary heart disease, hyperlipidemia, etc., which are all thought to be related to fiber deficiency, in Western countries compared to Japan might be due to the differences in the IS ratio. Conclusions: A decline in total DF intake and DF density is predicted for Japan in the future, because these parameters were lower among the younger generation. This may be due to the marked changes in the dietary habits of the younger generation, and is a problematic trend for Japanese health. Received: 26 April 2002, Accepted: 22 August 2002 Correspondence to: Shigeyuki Nakaji, MD, PhD     

MMP-12 has a role in abdominal aortic aneurysms in mice

BACKGROUND: Matrix metalloproteinase (MMP)-12 levels are increased in the abdominal aortic aneurysm (AAA), implicating this protease in AAA pathogenesis. The purpose of this study was to assess the role of MMP-12 in aneurysm formation. METHODS: A murine aneurysm model was generated by periaortic application of 0.25 mol/L calcium chloride (CaCl 2 ) for 15 minutes. Aortic diameters were measured and compared before and 10 weeks after aneurysm induction. Aortic diameter changes for wild type (WT) and MMP-12 knockout (MMP-12 -/- ) mice were determined. MMP-12 production in mouse aorta was analyzed by casein zymography. MMP-2 and MMP-9 expressions were examined by gelatin zymography. Immunohistochemical study was used to measure macrophage infiltration into the aorta. RESULTS: There is an increase of 63 +/- 5% (mean +/- SEM) in aortic diameters of WT mice after CaCl 2 inductions, while MMP-12 -/- mice increased only 26 +/- 14%. Connective tissue staining of aortic sections from WT mice showed disruption and fragmentation of medial elastic fibers, while MMP-12 -/- mice showed only focal elastic lamellae breakdown. MMP-12 levels in WT mice were significantly increased after CaCl 2 treatment, whereas no MMP-12 was detected in MMP-12 -/- mice. There was no difference in the MMP-2 and MMP-9 productions between WT and MMP-12 -/- mice. Immunohistochemical analysis demonstrated that infiltrating macrophages in the aorta of MMP-12 -/- mice were significantly less than WT controls. CONCLUSIONS: MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage recruitment.     

Serotonergic modulation of two potassium currents in the pleural sensory neurons of Aplysia

1. The properties of membrane currents that were modulated by serotonin (5-HT) were investigated with two-electrode voltage-clamp techniques in sensory neuron somata isolated from the pleural ganglion of Aplysia californica. The modulatory effects of 5-HT were revealed by computer subtraction of current responses elicited in the presence of 5-HT from current responses elicited prior to the application of 5-HT. The complexities of the resulting 5-HT difference currents (I5-HT) suggested that 5-HT modulated more than one component of membrane current. 2. The 5-HT difference currents appeared to have at least two distinct components. One component was clearly evident at membrane potentials more negative than -10 mV was relatively voltage independent and did not inactivate. A second component was activated at membrane potentials more positive than -10 mV, had complex kinetics, and was highly voltage dependent. In an attempt to identify the membrane currents that were modulated by 5-HT, we compared the pharmacologic sensitivity of I5-HT to that of previously described K+ currents. 3. The two components of I5-HT had different sensitivities to agents that block K+ currents. The relatively voltage-independent component of I5-HT was not blocked by 2 mM 4-aminopyridine (4-AP) and was relatively insensitive to tetraethylammonium (TEA) (estimated Kd of 92 mM). In contrast, the voltage-dependent component of I5-HT was blocked by 4-AP (2 mM) and moderate concentrations of TEA (estimated Kd of 5 mM). 4. The K+ current blockers that were used to examine I5-HT were also used to examine voltage-activated membrane currents. Externally applied TEA blocked the delayed or voltage-dependent K+ current (IK.V) with an estimated dissociation constant (Kd) of 8 mM and a membrane current similar to the Ca2+-activated K+ current (IK.Ca) with an estimated Kd of 0.4 mM. In addition, externally applied 4-AP (2 mM) blocked IK.V. Thus TEA and 4-AP were equipotent in blocking both IK.V and the voltage-dependent component of I5-HT. 5. The suggestion that I5-HT contained multiple components was supported further by examining the modulatory effects of adenosine 3',5'-cyclic monophosphate (cAMP) that mediates some actions of 5-HT on membrane currents in these cells. cAMP difference currents (IcAMP) were similar to the relatively voltage-independent component of I5-HT. The subsequent addition of 5-HT to solutions already containing cAMP resulted in 5-HT difference currents similar to the voltage-dependent component of I5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)     

Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys

In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states.     

Characterization of the acid-labile subunit of the growth hormone-dependent insulin-like growth factor binding protein complex

The insulin-like growth factors (IGFs) circulate predominantly in a 150,000-dalton (150K) complex, the IGF-binding component of which appears to be an acid-stable 53K glycoprotein (BP-53). This study tested the hypothesis that an acid-labile subunit (ALS) reacts with the binding subunit to form the 150K complex. ALS activity was quantitated by the conversion of covalent BP-53-[125I]IGF-I tracer from about 60K to about 150K. DEAE-Sephadex chromatography of serum at pH 8.2 yielded separate peaks of 30-60K BP-53 immunoreactivity and 100-110K ALS which, when mixed, converted the BP-53 to 150K. Whole serum also contained 100-110K ALS not complexed with BP-53. ALS was markedly acid labile, irreversibly losing activity below pH 4.5. In an assay involving competition between test substances and BP-53-IGF-I tracer in the reaction with partially purified ALS, serum samples, acidified to inactivate endogenous ALS, reacted with potencies proportional to their immunoreactive BP-53 content. Pure BP-53 alone was inactive, but after preincubation with IGF-I or IGF-II, competed with a potency identical to that of BP-53 in acidified serum. Amniotic fluid IGF-binding protein, with or without IGFs, had no activity. These results confirm that serum contains an acid-labile protein which interacts with the acid-stable IGF-binding protein BP-53, when it is occupied by IGFs, to convert it to the 150K form.