[Clinical analysis of 81 cases of intravenous leiomyomatosis confined to pelvic cavity].

Objective: To investigate the clinical features, treatment and recurrence factors of intravenous leiomyomatosis (IVL) confined to the pelvic cavity after the operation. Methods: The clinical data of 81 patients who underwent surgery and were pathologically diagnosed with IVL at Women's Hospital, School of Medicine, Zhejiang University from January 2014 to March 2021, were analyzed retrospectively to explore the influencing factors of postoperative recurrence of IVL, including age, gravidity and parity, surgical methods, intraoperative conditions and so on. Results: (1) Clinical features: the age of 81 IVL patients was (43.9±8.1) years old; increased menstrual volume in 26 cases (32%, 26/81), prolonged menstrual period in 31 cases (38%, 31/81), frequency and urgency to urinate in 4 cases (5%, 4/81), abdominal pain and abdominal distension in 8 cases (10%, 8/81), and pelvic masses in 34 cases (42%, 34/81). IVL was diagnosed right in 4 of 72 patients (6%, 4/72) underwent preoperative ultrasound, right in 11 of 51 patients (22%, 11/51) underwent magnetic resonance imaging (MRI), and right in 4 of 19 patients (4/19) underwent CT. (2) Treatment: all patients with IVL underwent surgical treatment. Surgical procedure: myomectomy in 37 cases, total hysterectomy and bilateral salpingectomy in 19 cases, total hysterectomy and bilateral salpingo-ophorectomy in 25 cases. Surgical approach: hysteroscopic operation in 6 cases, transabdominal operation in 52 cases, laparoscopic operation in 23 cases. Fifty-three cases underwent rapid intraoperative pathological examination, 17 cases (32%, 17/53) of them were diagnosed right as IVL. (3) Influencing factors of IVL postoperative recurrence: among 81 patients with IVL, 3 cases were lost to follow-up, and 8 cases (10%, 8/78) had recurrence during follow-up. Age<35 years, number of pregnancies<2, number of births<2, number of fibroids ≥10, abnormal appearance of fibroids (long, vermicular, beadlike, cystic, etc.) and IVL invasion into adjacent vessels were all the risk factors influencing postoperative recurrence of IVL (all P<0.05). Methods of operation, ovariectomy or not, IVL invasion or not, maximum diameter of IVL, abundant blood vessels near uterine fibroids were not associated with postoperative recurrence of IVL (all P>0.05). Conclusions: The clinical manifestations and preoperative auxiliary examination of IVL are lack of specificity. Doctors need to pay attention to young patients with uterine fibroids, and choose the appropriate surgical scope when the characteristic manifestations of IVL be found during the operation, or the right diagnoses of IVL in the surgery's rapid intraoperative pathology be examined, and should remove the IVL lesions to reduce the recurrence as far as possible.

MiR-223-5p inhibitor suppresses microglia inflammation and promotes Nrg-1 in rats of spinal cord injury.

OBJECTIVE: The aim of this study was to investigate the role of microRNA-233-5p (miR-233-5p) in spinal cord injury (SCI), and to explore the possible underlying mechanism. MATERIALS AND METHODS: Microglia were first isolated from neonate rats and cultured in a suitable environment in vitro. Lipopolysaccharide (LPS) and interleukin-4 (IL-4) were used to activate microglia. The expressions of miR-223-5p, inducible nitric oxide synthase (iNOS) and arginase 1 (Arg-1) were measured by qRT-PCR, respectively. After transfection of miR-233-5p inhibitor, the expression levels of miR-223-5p, iNOS and Arg-1 in cells were detected as well. A moderate SCI model was successfully established in rats (10 g fallen on T10 spinal cord at the height of 5 cm). Subsequently, inflammation indexes at miR-223-5p peak moment were observed. Meanwhile, its neuro-protective effect at 28 days after SCI was estimated. Finally, Basso, Beattie, and Bresnahan (BBB) rating scale was applied to evaluate the hindlimb locomotor function of rats at 1, 3, 7, 14, 21, 28 days after SCI. RESULTS: MiR-223-5p inhibitor significantly promoted M2 microglia expression and degenerated M1 microglia expression in vitro. SCI elevated the level of miR-223-5p in injured spinal cord tissues within one week, which reached a peak at 5 days after injury. Meanwhile, miR-223-5p inhibitor remarkably reduced the expressions of inflammatory factors, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) at 3 days after SCI, as well as increased neuregulin1 (NRG-1) expression. However, miR-223-5p inhibitor significantly declined the levels of apoptosis key enzyme-caspase-3 and glia reaction marker-glial fibrillary acidic protein (GFAP) at 7 and 28 days after SCI, respectively. As a result, BBB rating scale demonstrated that hindlimb locomotor function was significantly recovered in miR-223-5p injection group. CONCLUSIONS: MiR-223-5p was up-regulated in M1 microglia, whereas down-regulated in M2 microglia. MiR-223-5p inhibitor could significantly increase M2 microglia expression, while decrease M1 microglia expression in vitro. In vivo, miR-223-5p inhibitor suppressed the inflammatory response and reinforced NRG-1 level to reduce glia reaction and neuron apoptosis. Thereby, its treatment promoted the hindlimb locomotor function of rats.

Somatotopic Representation of Second Pain in the Primary Somatosensory Cortex of Humans and Rodents.

There is now compelling evidence that selective stimulation of Aδ nociceptors eliciting first pain evokes robust responses in the primary somatosensory cortex (S1). In contrast, whether the C-fiber nociceptive input eliciting second pain has an organized projection to S1 remains an open question. Here, we recorded the electrocortical responses elicited by nociceptive-specific laser stimulation of the four limbs in 202 humans (both males and females, using EEG) and 12 freely moving rats (all males, using ECoG). Topographical analysis and source modeling revealed in both species, a clear gross somatotopy of the unmyelinated C-fiber input within the S1 contralateral to the stimulated side. In the human EEG, S1 activity could be isolated as an early-latency negative deflection (C-N1 wave peaking at 710-730 ms) after hand stimulation, but not after foot stimulation because of the spatiotemporal overlap with the subsequent large-amplitude supramodal vertex waves (C-N2/P2). In contrast, because of the across-species difference in the representation of the body surface within S1, S1 activity could be isolated in rat ECoG as a C-N1 after both forepaw and hindpaw stimulation. Finally, we observed a functional dissociation between the generators of the somatosensory-specific lateralized waves (C-N1) and those of the supramodal vertex waves (C-N2/P2), indicating that C-fiber unmyelinated input is processed in functionally distinct somatosensory and multimodal cortical areas. These findings demonstrated that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire.SIGNIFICANCE STATEMENT Unmyelinated C-fibers are the evolutionarily oldest peripheral afferents responding to noxious environmental stimuli. Whether C-fiber input conveys information about the spatial location of the noxious stimulation to the primary somatosensory cortex (S1) remains an open issue. In this study, C-fibers were activated by radiant heat stimuli delivered to different parts of the body in both humans and rodents while electrical brain activity was recorded. In both species, the C-fiber peripheral input projects to different parts of the contralateral S1, coherently with the representation of the body surface within this brain region. These findings demonstrate that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire.

[Radiographic assessment of vertebral artery injury in anterior cervical surgery in healthy adults].

Objectives: To study the relationship between the anatomical parameters of transverse foramen and intervertebral discs in the cross-section of the cervical spine in healthy adults, and to evaluate the risk of vertebral artery injury in the anterior cervical spine surgery. Methods: There were 24 healthy adults(12 male, 12 female) underwent neck CT angiography with clear vertebral artery and the adjacent structure imaging from June to December 2014 in Huashan Hospital, Fudan University. The anatomical parameters of vertebral artery V2 segment with lower cervical vertebrae and intervertebral discs were measured by cross-sectional images of C(3-6). The corresponding parameters of different sex and both sides of the same segment were analyzed by independent samples t-test and paired t test, respectively. The least significant difference(LSD) t test was used to compare the corresponding data between different segments. Results: The vertebral artery was not walking in the middle of the transverse foramen in healthy individual, but partial medial, partial front walking. Transverse diameter of transverse foramen in male and female were 6.62-6.89 mm and 6.21-6.45 mm, and sagittal diameter was 5.41-6.48 mm and 5.40-6.10 mm, respectively.The transverse foramen were slightly oval. The distance between vertebral artery and midline in male and female were 14.23-16.12 mm and 13.60-15.04 mm, respectively, which was much larger than the width of cervical vertebral corpectomy. Compared with C(3-4), intervertebral disc, the transverse distance between the vertebral artery and the uncovertebral joint of C(4-5), C(5-6) was smaller, and the distance from the vertebral artery to the posterior margin of the uncovertebral joint was relatively small, the difference was statistically significant (t=2.449, P=0.022). The distance from vertebral artery to the posterior margin of uncinate process was 1/5-2/5 of the distance between the anterior and posterior edge of the corresponding segmental vertebra. Conclusion: Based on this anatomical study, the risk of vertebral artery injury in conventional anterior cervical decompression is small, and the risk of vertebral artery injury in different segments is slightly different.

Biological mechanism of post-herpetic neuralgia: Evidence from multiple patho-psychophysiological measures.

BACKGROUND: Post-herpetic neuralgia (PHN), which develops after the resolution of a herpes zoster eruption, is an exceptionally drug-resistant neuropathic pain. The unsatisfactory management of PHN partly results from the difficulty in dissecting out its contributing factors due to the complexity of PHN mechanism. METHODS: Here, to elaborate our understanding of the PHN mechanism and to establish a basis for effective therapeutic strategies, we comprehensively investigated the contributions of multiple factors to PHN severity. RESULTS: Based on the comparison of somatosensory detection thresholds (C, Aδ and Aß fibre thresholds) between affected and unaffected sides, 16 PHN patients with significant sensory deficits and 13 PHN patients without significant sensory deficits were identified and assigned to different groups. The different extents of lesions in the nociceptive system between patients with and without sensory deficits were confirmed using laser-evoked brain responses. Moreover, patients with sensory deficits had more severe pain and psychological disorders, e.g. anxiety and depression. Importantly, chronic pain severity was significantly influenced by various psychophysiological factors (sleep disturbances, psychological disorders and hypothalamic-pituitary-adrenal axis dysfunction) for patients with sensory deficits. CONCLUSIONS: Our findings demonstrated the contribution of multiple patho-psychophysiological factors to PHN severity, which could help establish a basis for the development of a rational, patient-centred therapeutic strategy. SIGNIFICANCE: This study revealed the contribution of multiple patho-psychophysiological factors to PHN severity, which expanded our understanding of the underlying PHN mechanism, and helped develop a rational, patient-centred therapeutic strategy targeting towards the corresponding etiology and psychophysiological disorders for individual patient.

Salicylic acid-induced changes in physiological parameters and genes of the flavonoid biosynthesis pathway in Artemisia vulgaris and Dendranthema nankingense during aphid feeding.

Phloem-feeding aphids cause serious damage to plants. The mechanisms of plant-aphid interactions are only partially understood and involve multiple pathways, including phytohormones. In order to investigate whether salicylic acid (SA) is involved and how it plays a part in the defense response to the aphid Macrosiphoniella sanbourni, physiological changes and gene expression profiles in response to aphid inoculation with or without SA pretreatment were compared between the aphid-resistant Artemisia vulgaris 'Variegata' and the susceptible chrysanthemum, Dendranthema nankingense. Changes in levels of reactive oxygen species, malondialdehyde (MDA), and flavonoids, and in the expression of genes involved in flavonoid biosynthesis, including PAL (phenylalanine ammonia-lyase), CHS (chalcone synthase), CHI (chalcone isomerase), F3H (flavanone 3-hydroxylase), F3'H (flavanone 3'-hydroxylase), and DFR (dihydroflavonol reductase), were investigated. Levels of hydrogen peroxide, superoxide anions, MDA, and flavonoids, and their related gene expression, increased after aphid infestation and SA pretreatment followed by aphid infestation; the aphid-resistant A. vulgaris exhibited a more rapid response than the aphid-susceptible D. nankingense to SA treatment and aphid infestation. Taken together, our results suggest that SA could be used to increase aphid resistance in the chrysanthemum.

Laser-evoked cortical responses in freely-moving rats reflect the activation of C-fibre afferent pathways.

The limited success of translating basic animal findings into effective clinical treatments of pain can be partly ascribed to the use of sub-optimal models. Murine models of pain often consist in recording (1) threshold responses (like the tail-flick reflex) elicited by (2) non-nociceptive specific inputs in (3) anaesthetized animals. The direct cortical recording of laser-evoked potentials (LEPs) elicited by stimuli of graded energies in freely-moving rodents avoids these three important pitfalls, and has thus the potential of improving such translation. Murine LEPs are classically reported to consist of two distinct components, reflecting the activity of Aδ- and C-fibre afferent pathways. However, we have recently demonstrated that the so-called "Aδ-LEPs" in fact reflect the activation of the auditory system by laser-generated ultrasounds. Here we used ongoing white noise to avoid the confound represented by the early auditory response, and thereby comprehensively characterized the physiological properties of C-fibre LEPs recorded directly from the exposed surface of the rat brain. Stimulus-response functions indicated that response amplitude is positively related to the stimulus energy, as well as to nocifensive behavioral score. When displayed using average reference, murine LEPs consist of three distinct deflections, whose polarity, order, and topography are surprisingly similar to human LEPs. The scalp topography of the early N1 wave is somatotopically-organized, likely reflecting the activity of the primary somatosensory cortex, while topographies of the later N2 and P2 waves are more centrally distributed. These results indicate that recording LEPs in freely-moving rats is a valid model to improve the translation of animal results to human physiology and pathophysiology.

Identification and expression analysis of the MSP130-related-2 gene from Hyriopsis cumingii.

MSP130-related-2 is thought to play a role in bio-mineralization as revealed in Crassostrea gigas and sea urchins. In this study, an MSP130-related-2 gene was isolated from Hyriopsis cumingii (HcMSP130-related-2) and characterized for the first time. The HcMSP130-related-2 cDNA was 2307 bp in length and consisted of a 572-bp 5'-untranslated region (5'-UTR), a 1239-bp open reading frame encoding 430-amino acid residues, and a 439-bp 3'-UTR. The molecular weight of the peptide was predicted to be 48551.3 Da, with a theoretical isoelectric point of 4.78 and instability index of 32.74, indicating that the protein is stable. The HcMSP130-related-2 amino acid residues included a signal peptide and several potential N-glycosylation sites. NCBI BLAST analysis indicated that this full-length amino acid sequence showed the highest similarity with HcMSP130-related-2 from C. gigas (45%) and about 38% identity with that from SpMSP130-rel-2 and Strongylocentrotus purpuratus. A phylogenetic tree showed that HcMSP130-rel-2 clustered with MSP130 from C. gigas. HcMSP130-related-2 was expressed in various tissues, including the mantle, blood, gill, foot, liver, kidney, intestine, and muscle, with the highest transcripts found in the mantle. Quantitative real-time polymerase chain reaction was used to analyze the expression of the HcMSP130- related-2 gene in grass carp after inducing shell damage. HcMSP130- related-2 expression was upregulated significantly in the mantle within 7 days (P < 0.05) after damage; however, the expression remained unchanged in the adductor muscle tissues (P > 0.05). These data suggest that HcMSP130-related-2 might be involved in shell formation in H. cumingii.

Molecular characterization and expression patterns of the big defensin gene in freshwater mussel (Hyriopsis cumingii).

Antimicrobial peptides (AMPs), of which big defensins are examples, are an important component of the natural defenses of most living organisms, and possess remarkable microbicidal activities. In the present study, using expressed-sequence tag sequences from a cDNA library and RACE, the full-length cDNA sequence of the big defensin gene from the triangle-shell pearl mussel, Hyriopsis cumingii, (HcBD), was cloned. The gene consists of a 5'-untranslated region (UTR) of 166 bp, a 3'-UTR region of 96 bp, and an open reading frame of 342 bp that encodes 113 amino acids, consisting of a 23 amino acid signal peptide and a mature peptide of 90 amino acids with a molecular mass of 12.5 kDa. Amino acid sequence analysis showed that the sequence contained a transmembrane domain and a hydrophobic region. The full-length amino acid sequence showed the highest similarity to an amphioxus (Branchiostoma floridae) sequence (64%), and lower similarities to other known defensins (α-, ß-, and θ-defensins, and insect defensins). Expression of HcBD was relatively high in the mantle and blood, lower in other tested tissues, and absent in gill and foot tissues. Real-time quantitative PCR was used to investigate HcBD expression in various tissues at different time points after injection of Aeromonas hydrophila. At 4 h post-inoculation, HcBD expression in the mantle, liver, intestine, gill, and foot was greater than in the control, with the greatest expression at 72 h, while at 24 h, expression in the liver, intestine, gill, and foot were at their lowest levels. These results suggest that HcBD might play an important role in the host immune response. This study enriches the basic research on the big defensin family of antimicrobial peptides and lays foundations for further research on antimicrobial peptide expression and relevance to disease defense.

Photo-responsive properties of azobenzene small molecules in sol-gel hybrid TiO(2)/ormosil organic-inorganic matrices.

Azodye-doped TiO(2)/ormosil hybrid materials for photonic applications were prepared by a low temperature sol-gel process from an organic-inorganic hybrid system. Acid-catalyzed solutions of gamma-glycidoxypropyltrimethoxysilane and methyltrimethoxysilane mixed with tetrapropyl orthotitanate were used as hybrid matrix precursors. The trans-cis-trans photoisomerization of azobenzene small molecules in sol-gel hybrid organic-inorganic matrices was induced by a photoirradiation with UV light and subsequent visible light. It was found that the hybrid film doped with azodyes and heated at a lower temperature was much better for applications in optical storage or optical switch. The planar waveguide properties of the hybrid films were also investigated by using a prism coupling technique. These results indicates that it is possible for the as prepared hybrid films to allow directly integrating on the same chip the optical storage or optical switch devices with the pump source.

A two year family based behaviour treatment for obese children.

BACKGROUND: Childhood obesity has become a nutritional problem in China since the 1990s. AIMS: A family based behavioural treatment was developed and tested, to see if its use was feasible in China and to evaluate its impact on obese schoolchildren. METHODS: In a single school in Beijing, 33 obese children were randomly assigned to a treatment group and 35 to a control group. The treatment group participated in a family based behavioural treatment programme for two years. Height and weight were measured every six months for all participants. Blood pressure, cholesterol, and triglyceride levels were measured at baseline and after two years of programme implementation. RESULTS: Body mass index (BMI, kg/m2) was significantly reduced in the treatment group (from 26.6 (1.7) to 24.0 (0.9), 95% CI 2.06 to 3.18) but not in the control group (from 26.1 (1.5) to 26.0 (1.6)). Total cholesterol decreased 5.5% and triglycerides 9.7% in the treatment group. There was a significant correlation between change in BMI and change in triglycerides. There were no significant changes in plasma lipids in the controls. Blood pressure values also decreased significantly in the treatment, but not the control group. CONCLUSIONS: A family based behavioural intervention was feasible to use in treating obesity in schoolchildren in Beijing, China. After two years of implementation, it successfully decreased the degree of obesity, reduced levels of blood pressure, and decreased serum lipids in treatment; there were no significant changes among control children.

Hypoxia activates jun-N-terminal kinase, extracellular signal-regulated protein kinase, and p38 kinase in pulmonary arteries.

Chronic alveolar hypoxia is the major cause of pulmonary hypertension. The cellular mechanisms involved in hypoxia- induced pulmonary arterial remodeling are still poorly understood. Mitogen-activated protein kinase (MAPK) is a key enzyme in the signaling pathway leading to cellular growth and proliferation. The purpose of this investigation was to determine the roles that MAPKs, specifically Jun-N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38 kinase, play in the hypoxia-induced pulmonary arterial remodeling. Rats were exposed to normobaric hypoxia (10% O(2)) for 1, 3, 7, or 14 d. Hypoxia caused significant remodeling in the pulmonary artery characterized by thickening of pulmonary arterial wall and increases in tissue mass and total RNA. JNK, ERK, and p38 kinase tyrosine phosphorylations and their activities were significantly increased by hypoxia. JNK activation peaked at Day 1 and ERK/p38 kinase activation peaked after 7 d of hypoxia. The results from immunohistochemistry show that hypoxia increased phospho-MAPK staining in both large and small intrapulmonary arteries. Hypoxia also upregulated vascular endothelial growth factor messenger RNA (mRNA) and platelet-derived growth factor receptor mRNA levels in pulmonary artery with a time course correlated to the activation of ERK and p38 kinase. The gene expressions of c-jun, c-fos, and egr-1, known as downstream effectors of MAPK, were also investigated. Hypoxia upregulated egr-1 mRNA but downregulated c-jun and c-fos mRNAs. These data suggest that hypoxia-induced activation of JNK is an early response to hypoxic stress and that activation of ERK and p38 kinase appears to be associated with hypoxia-induced pulmonary arterial remodeling.

PLA2-independent induction of CSF-1 gene expression in growth-arrested fibroblasts.

At the site of a wound or an infection, localized production of colony-stimulating factor-1 (CSF-1) by resident macrophages is chemotactic for circulating monocytes. Several intracellular signaling pathways, including those initiated in response to activation of phospholipase A2 (PLA2) have been proposed to play a role in the regulation of CSF-1 gene expression. The goal of these studies was to determine whether PLA2 is required for the initial increase in CSF-1 gene expression in serum- or IL-1 alpha-stimulated growth-arrested fibroblasts. IL-1 alpha- or serum-stimulation of growth-arrested fibroblasts had no effect on PLA2 enzyme activity and inhibitors of cytosolic or Ca(2+)-independent PLA2 activity had no effect on IL-1 alpha- or serum-mediated increases in CSF-1 mRNA levels. High concentrations of the PLA2 inhibitors, 4-bromophenacyl lactone and quinacrine, resulted in a generalized decrease in cellular mRNA levels. Our results, obtained in fibroblasts, suggest treatment with 4-bromophenacyl lactone or quinacrine, instead of inhibiting PLA2 activity specifically, results in a generalized depression of cellular mRNA levels. These data demonstrate that the initial increase in CSF-1 gene expression in growth-arrested fibroblasts treated with serum or IL-1 alpha occurs through a PLA2-independent mechanism.

Transcriptional regulation of the mouse CSF-1 gene.

Research in our laboratory is aimed at understanding the cellular and molecular mechanisms that govern colony stimulating factor-1 (CSF-1) gene expression. Our hypothesis is that a basal set of trans-acting factors is bound to the CSF-1 gene during fibroblast proliferation, resulting in constitutive CSF-1 gene expression. Modulation of CSF-1 gene transcription by growth-arrest (decrease) or stimulation of growth-arrested fibroblasts (re-initiate) is mediated by changes in the basal set of factors bound and/or by the addition of stimulus-specific factors. We have extended our hypothesis to include other cell types (monocytes) to determine if mechanisms used to control CSF-1 gene expression in fibroblasts are unique or represent common nontissue-specific regulatory mechanisms. Analysis of CSF-1-CAT reporter constructs in transiently transfected fibroblasts and monocytes was used to identify CSF-1 genomic sequences that affect transcriptional activity. DNase I protection, electrophoretic mobility shift, and methylation interference assays were used to identify the putative cis-acting elements. Results of our study suggest multiple trans-acting factors may regulate CSF-1 gene expression; some may be tissue specific, while others, such as AP1, CTF/NF1, Sp1, and Sp3, are shared in common.

Binding of a CTF/NF1-like protein to the mouse colony-stimulating factor-1 gene promoter.

Circulating and tissue-specific monocytes/macrophages, through production of hydrolytic enzymes and growth factors, can dramatically affect the local tissue environment. Colony-stimulating factor-1 (CSF-1) is a key regulator of monocyte/macrophage cell activity. CSF-1 is produced by stromal elements, including fibroblasts, which are found in all tissues. To understand at the molecular level how changes in CSF-1 gene transcription are initiated in fibroblasts, we set out to identify the cis-acting elements and cognate trans-acting factor(s) that bind regulatory regions of the mouse CSF-1 gene. Analysis of heterologous reporter constructs containing the mouse CSF-1 promoter linked to the bacterial chloramphenicol acetyltransferase (CAT) gene in transiently transfected fibroblasts identified a cis-acting element located between base pairs -88 and -43 of the CSF-1 gene. Electrophoretic mobility-shift assays (EMSAs) and DNase I protection assays with nuclear extracts isolated from proliferating fibroblasts revealed distinct protein binding to the region spanning base pairs -90 to -68. Results from methylation interference assays suggest CTF/NF1 or a CTF/NF1-like factor is the cognate trans-acting factor. Mutation of the putative CTF/NF1 binding site in the CSF-1 promoter lead to a modest decrease in promoter activity in transiently transfected fibroblasts and monocytes. Therefore, we have demonstrated that CTF/NF1 or a CTF/NF1-like protein binds to the CSF-1 gene promoter; however, binding of the CTF/NF1-like protein alone does not significantly effect changes in CSF-1 gene promoter activity.

Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1.

Aflatoxin B1 (AFB1) has been postulated to be a hepatocarcinogen in humans, possibly by causing p53 mutations at codon 249. AFB1 is metabolized via the phase I and II detoxification pathways; hence, genetic variation at those loci may predict susceptibility to the effects of AFB1. To test this hypothesis, genetic variation in two AFB1 detoxification genes, epoxide hydrolase (EPHX) and glutathione S-transferase M1 (GSTM1), was contrasted with the presence of serum AFB1-albumin adducts, the presence of hepatocellular carcinoma (HCC), and with p53 codon 249 mutations. Mutant alleles at both loci were significantly overrepresented in individuals with serum AFB1-albumin adducts in a cross-sectional study. Mutant alleles of EPHX were significantly overrepresented in persons with HCC, also in a case-control study. The relationship of EPHX to HCC varied by hepatitis B surface antigen status and indicated that a synergistic effect may exist. p53 codon 249 mutations were observed only among HCC patients with one or both high-risk genotypes. These results indicate that individuals with mutant genotypes at EPHX and GSTM1 may be at greater risk of developing AFB1 adducts, p53 mutations, and HCC when exposed to AFB1. Hepatitis B carriers with the high-risk genotypes may be an even greater risk than carriers with low-risk genotypes. These findings support the existence of genetic susceptibility in humans to the environmental carcinogen AFB1 and indicate that there is a synergistic increase in risk of HCC with the combination of hepatitis B virus infection and susceptible genotype.

Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms' tumor locus.

Colony-stimulating factor-1 (CSF-1) is a member of the immediate early gene family, which is expressed in mitogen-stimulated quiescent fibroblasts. The biological effects of CSF-1 are multifaceted and include stimulation of the proliferation and differentiation of myeloid progenitors and activity of circulating monocytes and tissue-specific macrophages. Ablation of circulating levels of biologically active CSF-1 in mice leads to osteopetrosis and sterility, thus implicating a role for CSF-1 in bone remodeling and implantation. Identification of regulatory elements and cognate transcription factors that bind the csf-1 promoter and mediate such diverse expression patterns is of great interest. We identified a sequence element at -273 to -265 (relative to the transcription initiation site) in the murine csf-1 promoter, which contains overlapping consensus sequences for the Wilms' tumor protein (WT1), EGR-1, SP1, and SP3 proteins. WT1 and EGR-1 proteins produced in vitro bound to this sequence, and co-transfection of wt1 with a csf-1-cat reporter plasmid resulted in repression of promoter activity. Interestingly, nuclear extracts prepared from serum-stimulated C3H10T1/2 cells contained predominantly SP1 and SP3 binding activities, which recognized the -273 to -265 site. Thus repression of the csf-1 promoter by WT1 at this site may involve competition between SP1 family transcriptional activators and the WT1 repressor. Colony-stimulating factor-1 may be a physiologically relevant target gene for regulation by the WT1 transcription factor.

[Diagnosis and treatment of secondary bone cysts].

The article reported 17 cases of confirmed or suspected secondary bone cyst originating from cystic degeneration of pre-existed tumor or tumor-like lesions. Twelve cases were diagnosed as solitary bone cysts pathologically after operation, but their clinical or radiological manifestations were not in keeping with the pathological findings. Among them aggressive or malignant tumors appeared in 6 cases during follow-up and no primary lesions could be found in other 6 cases. The macroscopic features of the lesion of other 5 cases were very similar to a solitary bone cyst, nevertheless, primary tumors were found histologically. The authors held that when dealing with a cystic lesion of bone, it was important, but sometimes difficult to differentiate a solitary bone cyst from a secondary one, and suggested that if the latter was suspected, injection therapy should not be used, but more radical procedures should be taken for treatment instead and the patient should be observed closely for a longer period.

[Aggressive fibromatosis of bone].

Twenty four cases of pathologically diagnosed aggressive fibromatosis of bone were reported. 17 patients were followed for at least 2 years. Among them 4 recurred and the histological findings of their lesional tissues obtained after recurrence remained benign; one case refused radical treatment and the second biopsy done at 3.5 years after the appearance of the tumor showed no malignant changes; but another case died of lung metastasis. The authors suggest that the criteria for final diagnosis of an aggressive fibromatosis of bone are as follows: Besides the pathological findings, the lesion does not recur or metastasize more than 2 years after operation or it does recur, but still shows benign features histologically. As for treatment, marginal or wide excision is the procedure of choice.