Second-trimester sex hormone-binding globulin and subsequent development of pre-eclampsia.

OBJECTIVE: To investigate whether maternal plasma sex hormone-binding globulin (SHBG) concentrations are reduced in women who subsequently develop pre-eclampsia. METHODS: This was a cross-sectional study, carried out at antenatal clinics in seven hospitals in and around London. Healthy women underwent uterine artery Doppler velocimetry as a screening method for pre-eclampsia at 22-24 weeks of gestation. The first group (408 women) had normal uterine artery Doppler waveforms (mean uterine artery pulsatility index (PI) below 1.6). The second group (274 women) had increased impedance to flow in the uterine arteries (mean PI above the 95th centile, 1.6). Maternal plasma SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. Pre-eclampsia was as defined by the International Society for the Study of Hypertension in Pregnancy. RESULTS: Plasma SHBG concentrations in the 80 (11.7%) women who subsequently developed pre-eclampsia were significantly lower than in the 585 (85.8%) women with normal pregnancy outcomes (median 336, range 142-674 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.001). There was a strong correlation between SHBG concentrations and body mass index (r =-0.232246, p < 0.0001). There were no significant differences in maternal plasma SHBG concentrations in women with abnormal uterine artery Doppler (n = 274) compared with controls (n = 408) (median 324, range 101-635 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.09). CONCLUSION: Maternal plasma SHBG concentrations are reduced in women who subsequently develop pre-eclampsia.     

Clinical and laboratory characteristics of cerebral infarction in tuberculous meningitis: a comparative study.

Cerebral infarction as a complication of tubercular (TB) meningitis is not uncommon, but an adequate comparison of patients with and without stroke has not been carried out. This study was performed to evaluate the clinical characteristics of cerebral infarction secondary to TB meningitis, and to investigate predictive factors for cerebral infarction in patients with TB meningitis. Patients with TB meningitis were recruited over a period of 56 months. They were divided into two groups, those with and those without stroke. Demographic features and clinical, laboratory, and neuroradiological findings were compared between the two groups. We classified strokes into subtypes using neuroimaging findings. Of the 38 patients who were diagnosed with TB meningitis, eight also experienced cerebral infarction. The percentage of cerebrospinal fluid leukocytes that were neutrophils was significantly higher in patients with stroke (68%) than in patients without stroke (31%; p=0.0001). Upon initial CT imaging, meningeal enhancement was found in 11 patients, and of these patients, six experienced stroke. There were no significant differences between the groups with respect to other clinical and laboratory features, including demographic features, time between meningitis onset and treatment initiation, peripheral white blood cell count, and cerebrospinal fluid findings. Five of the eight patients who developed stroke had lacunar infarcts. One of the three patients with territorial nonlacunar infarction died due to herniation. When treating patients with TB meningitis, the possibility of cerebral infarction should be considered when patients develop focal neurological signs, meningeal enhancement on a CT scan, and sustained polymorphic cerebrospinal fluid pleocytosis.     

肝癌患者血清12种肿瘤标志物的变化

目的探讨定量测定肝癌患者血清12种肿瘤标志物的临床意义。方法用蛋白芯片技术定量测定42例正常人、46例肝癌、41例肝炎和23例肝硬化患者血清12种肿瘤标志物的变化并对检测效果进行评价。结果42例正常人CA-199(KU/L)、NSE(g/L)、CEA(g/L)、CA-242(KU/L)、Ferritin(g/L)、β-HCG(g/L)、AFP(g/L)、f-PSA(g/L)、PSA(g/L)、CA-125(KU/L)、HGH(g/L)和CA-153(KU/L)的含量分别为12.42±10.62、2.22±1.43、1.28±1.20、5.72±5.73、91.17±79.43、0.64±0.34、2.96±3.93、0.13±0.11、0.61±1.40、5.46±9.65、1.61±2.40、9.83±9.51;46例肝癌患者血清12种肿瘤标志物含量依次为:35.09±39.50、2.83±4.13、2.98±8.72、8.47±23.42、157.50±129.77、0.72±0.72、87.58±63.27、0.15±0.19、0.58±1.88、56.34±102.02、3.63±4.57、15.65±51.09;41例肝炎患者其含量依次为:76.23±96.57、4.12±4.94、2.06±3.92、4.68±6.99、298.76±326.82、1.00±0.74、63.16±91.76、0.11±0.006、0.27±0.94、18.57±36.60、3.63±4.00、6.13±6.86;23例肝硬化患者其含量依次为:49.85±75.60、5.47±14.97、1.71±1.77、12.44±34.55、278.32±326.82、0.70±0.54、52.89±98.28、0.22±0.21、2.24±4.36、111.50±191.99、2.15±0.99、10.51±15.79。该蛋白芯片测定的敏感性为50.0%,特异性为64.2%,阳性预测值为37.7%,阴性预测值为74.7%。结论采用蛋白芯片技术同时测定患者血清多种肿瘤标志物,对普查肿瘤和临床疗效观察有较好应用价值。     

Cigarette smoke toxicants alter growth and survival of cultured mammalian cells.

Our purpose was to determine the effects of six cigarette toxicants (pyridine, nicotine, 2-ethylpyridine, 3-ethylpyridine, p-cresol, and pyrazine) on three types of cultured mammalian cells (human umbilical vein endothelial cells [HUVECs], human microvascular endothelial cells [HMVECs], and NIH 3T3 cells) using a cell proliferation/survival assay. Synchronized cells were cultured in proliferation or survival medium containing various doses (10(-18)M-10(-2)M) of the tested chemicals. After 48 h, cells were counted using a hemacytometer. The no observable adverse effect level (NOAEL), lowest observable adverse effect level (LOAEL), and the efficacy were determined for each compound in the cell proliferation and survival assays. Pyridine and p-cresol did not show significant effects with any cell types, except at high doses. Derivitization of the pyridine ring altered its potency, especially when an ethyl group or nitrogen was added. In survival medium, nicotine stimulated proliferation of all three cell types at doses found in smoker's serum (10(-8)M-10(-7)M). For HUVEC and HMVEC, 2-ethylpyridine, 3-ethylpyridine, and pyrazine inhibited proliferation in proliferation medium and induced cell death in survival medium at attomolar and femtomolar doses. All chemicals, except pyridine and pyrazine, stimulated NIH 3T3 cell proliferation at low doses and induced cell death at high doses. LOAELs and efficacies revealed that endothelial cells from a developing organ (umbilical cord) were more sensitive to these chemicals than endothelial cells from an adult organ (lung). 3-Ethylpyridine and pyrazine, which induced cell death at low doses, are added to consumer products and should be subjected to further toxicological testing.     

Effects of cerulenin on the endogenous fatty acid synthetic activity in squamous cell carcinoma of the oral cavity.

PURPOSES: Inhibition of cerulenin on the endogenous fatty acid synthetic activities of oral squamous cell carcinoma (OSCC) and normal oral mucosa was assayed. METHODS: Squamous cell carcinoma and normal oral mucosa were collected fresh from surgical specimens. The collected tissues were minced in RPMI 1640 and divided into 3 groups: cerulenin treated, dimethylsulfoxide treated, and control. The tissues were incubated in [1(2)-(14)C]acetic acid, sodium salt for the last 2.5 hours of the treatment at 37 degrees C in 5% CO(2). After labeling, total lipids were extracted and counted for (14)C by scintillation counting. RESULTS: Endogenous fatty acid synthetic activities of oral squamous cell caranoma in the cerulenin-treated group decreased by 19% at 1 hour, 64% at 2 hours, and 87% at 4 hours; remained nearly unchanged in the dimethylsulfoxide-treated group; and increased slightly in the control group. The oral mucosa tissues were only mildly affected by cerulenin in fatty acid synthesis. CONCLUSIONS: Cerulenin significantly inhibits fatty acid synthetic activity in squamous cell carcinoma and only mildly affected the oral mucosa, indicating that the fatty acid synthetic pathway may be exploited as a target for developing anticancer drugs.     

A comparative study of using comet assay and gammaH2AX foci formation in the detection of N-methyl-N'-nitro-N-nitrosoguanidine-induced DNA damage.

Comet assay is a useful technique in the detection of DNA damages, particularly DNA strand breaks; and it has been utilized to show that a potent carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), can induce such damages. Recently, gammaH2AX foci formation has been suggested as another sensitive way to detect DNA double strand breaks (DSBs). However, there is no systematic comparison being conducted to evaluate the consistency of these two methods. Using MNNG as a model chemical, the sensitivity of neutral comet assay and gammaH2AX foci formation in detecting MNNG-induced damage was studied. It was found that at concentrations of 0.1 and 1 microg/ml, both methods can detect MNNG-induced damage in human amnion FL cells. However, at 0.1 microg/ml, comet assay revealed more percentage of cells with DNA damage than gammaH2AX fluorescence revealed. On the other hand, while gammaH2AX foci were readily formed at very early times by 10 microg/ml MNNG treatment, neutral comet assay did not detect any significant DNA damage at the same time points. In addition, 10 microg/ml MNNG induced a distinct whole nuclei staining pattern of gammaH2AX, a type of DNA damage which was not detected by neutral comet assay but could be detected by alkaline comet assay. Therefore, gammaH2AX may be used as a sensitive indicator for DNA damage.     

Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans.

Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, but is also frequently demonstrated by children and adults with chronic obstructive lung diseases. AHR is usually measured by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare these two types of bronchial challenge in children with post-infectious bronchiolitis obliterans (BO). Methacholine and adenosine 5'-monophosphate (AMP) challenges were used as tools for the evaluation of AHR to direct and indirect stimuli, respectively, in children with post-infectious BO (n = 28). These results were compared with those of asthmatic (n = 30) and control children (n = 25). Altogether, twenty-two patients (78.6%) with post-infectious BO were hyperreactive to methacholine with a provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20) of <16 mg x mL(-1), but only six (21.4%) were hyperreactive to AMP with a PC20 of <200 mg x mL(-1). All patients with asthma responded positively to methacholine, and most (28, 93.3%) also responded positively to AMP. The majority of controls were insensitive to both challenges. Airway hyperresponsiveness to methacholine is a frequent, but by no means universal, finding in children with post-infectious bronchiolitis obliterans, but is usually not accompanied by airway hyperresponsiveness to adenosine 5'-monophosphate. This finding suggests that airway hyperresponsiveness in patients with post-infectious bronchiolitis obliterans has characteristics that differ from those of asthmatic subjects.     

Buccal mucosal graft for urethral reconstruction.

Urethral reconstruction with graft substances, such as skin and bladder mucosa, has been previously used when primary anastomosis cannot be achieved. However, stricture and meatal prolapse are associated with these grafts. We report the use of buccal mucosa for the reconstruction of urethral defects in 3 patients. One patient with failed operation for hypospadias received tube buccal mucosal graft for urethral replacement. Two patients with urethral necrosis and stricture received onlay buccal mucosal graft. All patients were disease-free during follow-up (range, 12 to 49 months; mean, 36 months). One patient had a pinhole fistula that was successfully managed with simple repair. This technique appears to be useful for urethral reconstruction when a local graft is not available, even in patients with complicated conditions.     

The CLDN5 locus may be involved in the vulnerability to schizophrenia.

The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3'-untranslated region of the CLDN5 locus was associated with schizophrenia (chi(2) = 4.75, P = 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5'-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (chi(2)) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (chi(2) = 5.32, P = 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors.     

Fumonisins as a possible contributory risk factor for primary liver cancer: A 3-year study of corn harvested in Haimen, China, by HPLC and ELISA

Employing HPLC fluorometry, gas-liquid chromatography (GLC) and a novel enzymelinked immunosorbent assay (ELISA) based on a monoclonal antibody, 40 corn samples, each collected in 1993 from agricultural stocks for human consumption in Haimen (Jiangsu County) and Penlai (Shandong Province), high- and low-risk areas for primary liver cancer (PLC) in China, respectively, were analysed for fumonisins (FBs), aflatoxins (AFs) and trichothecenes. Levels and positive rates of FBs and deoxynivalenol (DON) were significantly higher in Haimen than in Penlai. ELISA of the 40 corn samples harvested in the two areas in 1994 revealed that FB contamination levels and rates in these areas were comparable to those observed in 1993 in Haimen. ELISA analysis of 1993 and 1994 products revealed a wide occurrence of AFB₁ but the positive rates as well as levels were not significantly different between these areas. ELISA of the same sample number of corn harvested in 1995 revealed that FB contamination in Haimen was significantly higher than in Penlai. These 3-yearly surveys of corn samples (240 in total) demonstrated that corn harvested in Haimen was highly contaminated with FBs and that the contamination level, as well as positive rate in 1993 and 1995, were 10–50-fold higher than those in Penlai, suggesting FBs as a risk factor for promotion of PLC in endemic areas, along with the trichothecene DON. Co-contamination with AFs, potent hepatocarcinogens, was assumed to play an important role in the initiation of hepatocarcinogenesis.