ABSTRACT
Objective: Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) occurring at multiple sites during the same period of time is extremely rare, and the aim of this study was to investigate the clinicopathologic features of SMMN-FGT and its relationship with prognosis. Methods: We retrospectively analyzed the clinicopathological features and follow-up records of 25 cases of SMMN-FGT diagnosed from January 2012 to October 2022 in the case database of Obstetrics and Gynecology Hospital of Fudan University. Results: The mean and median age at onset were 47 and 46 years old, respectively. Clinical manifestations included irregular vaginal bleeding or drainage, pelvic pain, and ovarian cysts, etc. Germline genetic test confirmed Peutz-Jeghers syndrome (P-J syndrome) in two patients. All patients underwent surgery, and some had postoperative adjuvant radiotherapy and/or chemotherapy. The most frequent site of lesion was the cervix (21 cases), with 11, 10 and 16 cases occurring in the endometrium, fallopian tubes and ovaries, respectively. Six cases involved three sites simultaneously, and only one case had all four sites involved at the same time. Among the 9 cases with P53 mutation phenotype, 6 cases had gastric-type mucinous adenocarcinoma, 2 cases had lobular endocervical glandular hyperplasia, and 1 case had mucinous adenocarcinoma, whereas all the minimally deviated adenocarcinomas had wild phenotype of P53. The median follow-up time was 59 months, during which 3 cases died and 6 cases developed local recurrence or distant metastasis. According to our analysis, postoperative recurrence or metastasis was correlated with the FIGO stage of the disease, the number of lesion sites and the severe degree of the uterine lesions (Pï¼0.05). Conclusions: SMMN-FGT had a relatively good clinical prognosis, and even advanced patients could benefit from surgery and adjuvant therapy. In young patients, the ovaries may be preserved if no evidence of lesions were seen after adequate evaluation. In SMMN-FGT, gastric-type mucinous adenocarcinoma occurring in the cervix may have a better prognosis than gastric-type mucinous adenocarcinoma of the cervix alone, so the accurate diagnosis of SMMN-FGT is critical for clinical management.
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OBJECTIVE: This work was developed to compare the effects of transversus abdominis plane block (TAPB) and thoracic epidural anesthesia (TEA) mediated activation of inflammasome on postoperative medication, pain, and recovery in patients undergoing laparoscopic colorectal surgery. Then, the effects of two anesthesia methods on postoperative analgesia of patients were investigated and compared, aiming to provide reference for the selection of postoperative analgesia methods of laparoscopy. PATIENTS AND METHODS: In this work, patients undergoing laparoscopic colorectal surgery were rolled into a TAPB group (30 patients) and a TEA group (30 patients). The blood pressure and stress indexes of the patients at different time points were observed and compared, and the doses of anesthetic drugs were recorded. Postoperative pain scores were evaluated, and postoperative recovery of the two groups was compared. Meanwhile, the peripheral venous bloods were extracted from the two groups before and after surgery for the determination of inflammasome proteins, and the detection results were compared. RESULTS: Data showed that the dose of sufentanil in TEA group was notably inferior to that in TAPB group (p<0.05). The blood pressure indexes in the TEA group decreased remarkably (p<0.05), while their changes in the TAPB group were stable. The slower point heart rate (HR), lower mean arterial pressure (MAP), and lower levels of cortisol (Cor) and norepinephrine (NE) in the TEA group were found when compared with the TAPB group during the period from pneumoperitoneum establishment to post-ventilation. After pneumoperitoneum establishment, blood oxygen saturation (SpO2) in the TEA group was lower than that in the TAPB group at the same time point (p<0.05). The postoperative visual analog scales (VAS) score and numerical rating scale (NRS) score in TEA group were lower than those in TAPB group (p<0.05). After surgery, the protein level in TEA group was significantly lower than that in TAPB group (p<0.05). CONCLUSIONS: In short, the activation of inflammasome mediated by TEA could reduce the anesthetic agents used after laparoscopic colorectal cancer surgery and reduce the surgical stress response. In addition, TEA exerted a little effect on early immunity, which was safe and feasible, contributing to postoperative analgesia and recovery. In addition, its application value in laparoscopic postoperative analgesia was higher than TAPB.
Subject(s)
Anesthesia, Epidural , Colorectal Surgery , Laparoscopy , Pneumoperitoneum , Humans , Inflammasomes , Pneumoperitoneum/chemically induced , Pneumoperitoneum/surgery , Abdominal Muscles , Pain, Postoperative/surgery , Laparoscopy/adverse effects , Analgesics, OpioidABSTRACT
OBJECTIVE: Blast related characteristics may contribute to the diversity of findings on whether mild traumatic brain injury sustained during war zone deployment has lasting cognitive effects. This study aims to evaluate whether a history of blast exposure at close proximity, defined as exposure within 30 feet, has long-term or lasting influences on cognitive outcomes among current and former military personnel. METHOD: One hundred participants were assigned to one of three groups based on a self-report history of blast exposure during combat deployments: 47 close blast, 14 non-close blast, and 39 comparison participants without blast exposure. Working memory, processing speed, verbal learning/memory, and cognitive flexibility were evaluated using standard neuropsychological tests. In addition, assessment of combat exposure and current post-concussive, posttraumatic stress, and depressive symptoms, and headache was performed via self-report measures. Variables that differed between groups were controlled as covariates. RESULTS: No group differences survived Bonferroni correction for family-wise error rate; the close blast group did not differ from non-close blast and comparison groups on measures of working memory, processing speed, verbal learning/memory, or cognitive flexibility. Controlling for covariates did not alter these results. CONCLUSION: No evidence emerged to suggest that a history of close blast exposure was associated with decreased cognitive performance when comparisons were made with the other groups. Limited characterization of blast contexts experienced, self-report of blast distance, and heterogeneity of injury severity within the groups are the main limitations of this study.
Subject(s)
Blast Injuries , Brain Concussion , Military Personnel , Stress Disorders, Post-Traumatic , Humans , Blast Injuries/complications , Blast Injuries/psychology , Stress Disorders, Post-Traumatic/complications , Brain Concussion/complications , Brain Concussion/diagnosis , Cognition , Neuropsychological Tests , Iraq War, 2003-2011 , Afghan Campaign 2001-ABSTRACT
Primary Objective: To advance knowledge about the value of the Center for Epidemiologic Studies - Depression scale (CES-D) for depression screening in military service members with a history of mild traumatic brain injury (mTBI). Research Design: Retrospective data from 336 military service members with a history of mTBI were extracted from a TBI Repository at a large military medical center. Participants included in this study screened positive for mTBI in a primary care clinic or soldier readiness processing center and were enrolled in the TBI repository from November 6, 2014 to May 31, 2017. At the time of enrollment, participants completed the CES-D and their electronic medical records (EMR) were searched for diagnoses of depressive disorders. Methods and Procedures: Receiver-operating characteristic (ROC) analysis of the CES-D was used to discriminate cases with and without depression diagnoses. Main Outcomes and Results: Area under the ROC curve (AUC) was .897. Sensitivity (.824) and specificity (.826) were maximized at a cut score of 18 or greater, slightly higher than the standard cut of 16 established for civilian samples. Conclusions: Results suggest that the CES-D is a valid screening instrument for depressive disorders in military samples with a history of mTBI.
Subject(s)
Brain Concussion/complications , Depression/diagnosis , Military Personnel/psychology , Adult , Depression/etiology , Female , Humans , Male , Mass Screening , Psychiatric Status Rating Scales , Reproducibility of Results , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Objective: To explore the expression and clinicopathological significance of Ser10 phosphorylated p27(kip1)(P-p27Ser10) protein in human breast carcinoma tissue. Methods: Tissue specimens were obtained from 111 cases with breast carcinoma from January 2004 to December 2005. And the expression of P-p27Ser10 protein for each specimen was detected by immunohistochemical (EnVision) analysis. Six representative paired samples of cancerous and paired adjacent normal tissues were collected and detected by Western blot. The relationships between the expression levels of P-p27Ser10 protein and its clinicopathological characteristics in primary breast carcinoma were retrospectively analyzed.The association of P-p27Ser10 and Jab1 protein was detected by co-immunoprecipitation method. Results: A high-level expression of P-p27Ser10 was present in cancerous tissues but not in paired adjacent normal tissues. The positive expression rate of P-p27Ser10 protein was as high as 88.3% (98/111) and 7.2% (8/111) in cancerous and paired adjacent normal tissues respectively (P<0.05). P-p27Ser10 expression was correlated with tumor size, lymph node metastasis and TNM stage (all P<0.05). P-p27Ser10 expression was significantly correlated with Ki-67 (r=0.582, P<0.05), and inversely correlated with p27 (r=-0.426, P<0.05). Co-immunoprecipitation revealed that the association of P-p27Ser10 and Jab1 protein was increased in breast carcinoma. Conclusion: Over-expression of P-p27Ser10 protein might play an important role in the pathogenesis of breast carcinoma. P-p27Ser10 protein therefore represents a novel diagnostic marker and therapeutic target in patients with breast carcinoma.
Subject(s)
Breast Neoplasms/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry , Intracellular Signaling Peptides and Proteins , Lymphatic Metastasis , Peptide Hydrolases , PrognosisABSTRACT
Necrophoric behaviour is critical sanitation behaviour in social insects. However, little is known about the necrophoric responses of workers towards different developmental stages in a colony as well as its underlying mechanism. Here, we show that Solenopsis invicta workers display distinct necrophoric responses to corpses of workers and pupae. Corpses of workers killed by freezing (dead for <1 h) were carried to a refuse pile, but pupal corpses would take at least 1 day to elicit workers' necrophoric response. Metarhizium anisopliae-infected pupal corpses accelerated the necrophoric behaviour of resident workers, with 47.5% of unaffected corpses and 73.8% infected corpses discarded by 1 day post-treatment). We found that fungus-infected pupal corpses had a higher concentration of fatty acids (palmitic acid, oleic acid and linoleic acid) on their surface. We experimentally confirmed that linoleic and oleic acids would elicit a necrophoric response in workers. The appearance of linoleic and oleic acids appeared to be chemical signals involved in recognition of pupal corpses, and M. anisopliae infection could promote the accumulation of fatty acids on surface of pupal corpses resulting in accelerated necrophoric responses of workers.
Subject(s)
Ants/microbiology , Behavior, Animal , Animals , Ants/physiology , Behavior, Animal/drug effects , Host-Pathogen Interactions , Linoleic Acids/pharmacology , Oleic Acids/pharmacology , Pupa/microbiology , Social BehaviorABSTRACT
Tomato yellow leaf curl Kanchanaburi virus (TYLCKaV) is a bipartite begomovirus (genus Begomovirus, family Geminiviridae) reported to infect tomato and eggplant in Thailand and Vietnam (1,2). In April 2013, eggplant (Solanum melongena L.) plants exhibiting yellow mosaic symptoms were found in a suburb of Vientiane, Laos. Three symptomatic samples were collected. Total DNA was extracted from leaves by the CTAB method, and used as template for PCR using the degenerate primer pair AV494/CoPR (3). The PCR results suggested that the plants were infected by a begomovirus. The begomoviral genome was amplified by rolling circle amplification (RCA) with TempliPhi kit (GE Healthcare) following the manufacturer's protocol. RCA product was digested with the endonucleases BamH I, EcoR I, Hind III, Kpn I, Pst I, and Xba I, respectively. The fragments about 2.1 kbp (with Pst I digestion) and 1.5 kbp (with Xba I digestion) in size were cloned and sequenced. The sequence of the 2.1-kbp fragment showed similarity with begomovirus DNA-A component. A pair of primers for amplification of the full-length DNA-A, AF (5'-CTTCATCGTTTCTCAGCATCAT-3') and AR (5'-CACTTGCACACGATCTCTAAGA-3') were designed from the 2.1-kbp sequence. The full-length DNA-A was 2,752 nucleotides and encoded six putative ORFs (GenBank Accession No. KF218820). The sequence of the 1.5-kbp fragment shared similarity with begomoviruses DNA-B. The begomoviral circular DNA-B was amplified using the pair of primers BF (5'-GTAACAGCCGAAGTGCACG-3') and BR (5'-AATGGAGAGACACCAGTCTGCC-3') designed from the 1.5-kbp sequence. PCR yielded a product of expected size (~1.4 kbp). The full-length DNA-B sequence was obtained by assembling the two sequences. The DNA-B was 2,734 nucleotides and encoded two putative ORFs (GenBank Accession No. KF218821). The sequences of DNA-A and DNA-B of isolate Laos shared the highest nucleotide sequences identities at 99.0% and 98.0% with those of TYLCKaV-[TH:Kan 1:01] (AF511529), and [TH:Kan 2:Egg:01] (AF511527), respectively. The results indicated that the virus associated with eggplant yellow mosaic disease was an isolate of TYLCKaV. To our knowledge, this is the first report of this begomovirus in Laos. Our results indicate that this virus may be spreading in Southeast Asia and scientists there should be aware of this virus when developing begomovirus-resistant varieties of tomato or eggplant. References: (1) S. K. Green et al. Plant Dis. 87:446, 2003. (2) C. Ha et al. J. Gen. Virol. 89:312, 2008.(3) Z. F. He et al. Arch. Virol. 154:1199, 2009.
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To assess female sexual function (FSF) and health-related quality of life (HRQOL) following anterior vaginal wall surgeries for stress urinary incontinence (SUI) and pelvic organ prolapse (POP). The retrospective study consisted of 116 patients. Chinese translations of the modified Lemack Questionnaire (not validated) and Pelvic Floor Distress Inventory-Short Form 20 were used to assess FSF and HRQOL, 3 months pre-operatively and 12-24 months (mean 16.8 months) post-operatively. Sixty-one (52.6%, 29 in SUI group and 32 in POP group) of patients were sexually active before and after the operation. Overall, 12 (19.7%, six in SUI group and six in POP group) reported an improvement in overall intercourse satisfaction, 21 (34.4%, 8 in the SUI and 13 in the POP group) were decreased and 28 (45.9%, 15 in SUI group and 13 in POP group) were unchanged. Incidence of coital incontinence decreased significantly in SUI group. Frequency of intercourse decreased, vaginal dryness and pain due to it and asymptomatic vaginal narrowing increased significantly, following the surgery in POP group. There were no statistically significant differences in the frequency of intercourse in SUI group, patients' perception of intercourse, frequency of orgasm and the importance of sex life in both groups. Partner discomfort remained unchanged. HRQOL improved significantly after the operation in both groups. There was no association between HRQOL and FSF in the post-operative period. In most patients, overall FSF did not impaired. All trans-anterior vaginal wall surgery positively impacted on the patients' HRQOL. A prospective study with validated questionnaire is necessary in future.
Subject(s)
Pelvic Organ Prolapse/surgery , Postoperative Complications/epidemiology , Quality of Life , Sexual Behavior/statistics & numerical data , Urinary Incontinence, Stress/surgery , Adult , Aged , China/epidemiology , Female , Humans , Middle Aged , Retrospective Studies , Sexual Dysfunction, Physiological/epidemiologySubject(s)
Calcium/therapeutic use , Hydrofluoric Acid/poisoning , Magnesium/therapeutic use , Ventricular Fibrillation/etiology , Adult , Electrocardiography , Glucose/therapeutic use , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Male , Resuscitation , Survival , Treatment Outcome , Ventricular Fibrillation/therapyABSTRACT
AIM: To study the effect of bcr-abl fusion gene antisense phosphorothioate oligodeoxynucleotide (Aspo) on bcr-abl mRNA and apoptosis of K562 cells. METHODS: Cells were exposed to Aspo. P210 was measured by Flow Cytometry. Cellular bcr-abl mRNA was detected by RT-PCR mediquantitative analysis. Cell apoptosis was measured by Flow Cytometry and observed by electron microscope (EM). RESULTS: The P210 was down regulated or completely suppressed after 24h treatment with more than 5 micromol/L Aspo. The decrease of bcr-abl mRNA was about 45%. After incubation 48 h with 10 micromol/L Aspo. Also, 20% - 30% K562 cells were induced to apoptosis at 120 h when the cell number was 1 x 10(4)/ml at the beginning. While the cell number was 1 x 10(5)/ml, the apoptosis rate was 30% after 48 h culture and the typical morphology of apoptosis cell was observed under EM. CONCLUSION: bcr-abl Aspo could inhibit the expression of bcr-abl mRNA and P210. Also,it could induce apoptosis of K562 cells.
Subject(s)
Apoptosis/drug effects , Fusion Proteins, bcr-abl/genetics , Oligonucleotides, Antisense/pharmacology , Cell Proliferation/drug effects , Humans , K562 Cells , Phosphorothioate Oligonucleotides/pharmacology , RNA, Messenger/geneticsABSTRACT
OBJECTIVE: Patients who misperceive that they are moving their paralysed arm (phantom movements) may not recognise its weakness. Therefore, the relation between phantom limb movements and anosognosia for hemiplegia during selective right hemispheric anaesthesia (the Wada test) was examined. METHODS: Nine patients with intractable epilepsy underwent the Wada test. During the right hemispheric injection, after the onset of hemiparesis, anosognosia was assessed by asking patients if they were weak. The patient's vision was limited such that they could not see the position of their limbs. Phantom movements were tested for by asking patients to attempt to lift their left upper limb, and to demonstrate their left limb's position by placing their right limb in the same position as their left. Proprioception was tested by lifting the patient's paretic upper limb and having patients demonstrate this position by lifting their right limb to the same position. RESULTS: Three patients experienced left phantom limb movements, and five were anosognosic for their hemiplegia. However, phantom movement occurred in only one patient with anosognosia. The other two patients with phantom movement were without anosognosia. The patient with phantom movement and anosognosia had impaired proprioception. The two patients with phantom movement but without anosognosia had intact proprioception. CONCLUSIONS: Phantom movement in the presence of a proprioceptive deficit could contribute to anosognosia. However, anosognosia and phantom movement are dissociable; therefore phantom movement cannot alone account for anosognosia. Because phantom movement occurred with and without proprioceptive deficits, proprioceptive loss is not a prerequisite for phantom movement.
Subject(s)
Agnosia/psychology , Hemiplegia/physiopathology , Hemiplegia/psychology , Movement/physiology , Phantom Limb/physiopathology , Phantom Limb/psychology , Adult , Agnosia/physiopathology , Female , Humans , Male , Middle AgedABSTRACT
Holmes noted that with hemispheric injuries proprioceptive disturbances were more marked in the distal than proximal limb segments and proposed that this difference was related to the size of cortical sensory representations. An alternative hypothesis is that sensation from distal segments projects to the contralateral hemisphere and sensation from proximal segments projects to both hemispheres. Selective hemispheric anesthesia was used to test these alternative hypotheses and revealed a decrement in distal but not proximal proprioception with hemispheric anesthesia, thereby supporting the bilateral projection hypothesis.
Subject(s)
Epilepsy/complications , Functional Laterality , Somatosensory Disorders/diagnosis , Somatosensory Disorders/physiopathology , Arm , Electroencephalography , Humans , Methohexital , Reproducibility of Results , Shoulder , Somatosensory Disorders/complications , Temporal Lobe/pathology , Temporal Lobe/physiopathology , WristABSTRACT
This study was conducted to investigate the nature of root resorption resulting from intrusive forces applied to the rat lower molars, by means of histological and histochemical techniques with tartrate resistant acid phosphatase (TRAP). Thirty-eight 13-week-old Wistar strain male rats were used. Intrusive force was created by a fixed appliance which was adjusted to exert an initial force of 50 g for the duration of 1, 2, and 3 weeks. The degree of root resorption and distribution of TRAP positive cells were evaluated. On the root surface, the TRAP positive scores were low in the apical regions. Significant differences in the scores were found in the inter-radicular region of the roots between the experimental and control groups for the 2- and 3-week groups. More active resorption of bone occurred during the experimental period, as denoted by greater TRAP positive scores on the bone than on the root surface. Root resorption scores in the apical root region were larger in the 2- and 3-week groups than in the 1-week group. Significant differences in the root resorption scores were also found between the 1- and 3-week groups in the inter-radicular region, indicating that intrusive force application of a longer duration may lead to a higher frequency of root resorption. It is shown that, irrespective of the level of TRAP positive cells and root resorption scores, the degree of root resorption activity is higher in the apical root region than in the inter-radicular area. These results indicate that cellular cementum may be resorbed more easily because of its richer organic components and low mineralized structure.
Subject(s)
Molar/pathology , Root Resorption/pathology , Tooth Movement Techniques , Acid Phosphatase/analysis , Alveolar Bone Loss/metabolism , Alveolar Bone Loss/pathology , Analysis of Variance , Animals , Biomarkers/analysis , Coloring Agents , Dental Cementum/pathology , Isoenzymes/analysis , Male , Molar/metabolism , Rats , Rats, Wistar , Root Resorption/metabolism , Stress, Mechanical , Tartrate-Resistant Acid Phosphatase , Tooth Apex/pathology , Tooth Root/pathologyABSTRACT
1. The mechanisms of the antiproliferative effect of epigallocatechin, one of the catechin derivatives found in green tea, in vascular smooth muscle cells were studied. The proliferative response was determined from the uptake of tritiated thymidine. 2. In the concentration range of 10(-6) to 10(-4) M, catechin, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin, epigallocatechin gallate, concentration-dependently inhibited the proliferative response stimulated by serum in rabbit cultured vascular smooth muscle cells. Catechin and epicatechin were less effective in inhibiting the serum-stimulated smooth muscle cell proliferation, indicating that the galloyl group may be important for full inhibitory activity. 3. Epigallocatechin (EGC) inhibited the proliferative responses in different cells including rat aortic smooth muscle cells (A7r5 cells), rabbit cultured aortic smooth muscle cells, human coronary artery smooth muscle cells, and human CEM lymphocytes in a concentration-dependent manner. The possible mechanisms of the antiproliferative effect of EGC were further studied in A7r5 cells. 4. The membranous protein tyrosine kinase activity stimulated by serum in A7r5 cells was significantly reduced by 10(-5) M EGC. In contrast, the cytosolic protein kinase C activity stimulated by phorbol ester was unaffected by directly incubating with EGC (10(-6)-10(-4) M). 5. We also performed Western blot analysis using the anti-phosphotyrosine monoclonal antibody PY20. EGC (10(-5) M) reduced the levels of tyrosine phosphorylated proteins with different molecular weights, indicating that EGC may inhibit the protein tyrosine kinase activity or stimulate the protein phosphatase activity. 6. Reverse transcription-polymerase chain reaction analysis of c-fos, c-jun and c-myc mRNA levels demonstrated that c-jun mRNA level after serum-stimulation was significantly reduced by 10(-5) M EGC. However, the reduction of c-fos and c-myc mRNA levels by 10(-5) M EGC did not achieve significance. 7. Western blot analysis using the antibody against JNK (c-jun N-terminal kinase) and ERK (extracellular signal-regulated kinase) demonstrated that the level of phosphorylated JNK1, but not phosphorylated ERK1 and ERK2, was reduced by 10(-5) M EGC. Direct measurement of kinase activity by immune complex kinase assay confirmed that JNK1 activity was inhibited by EGC treatment. These results demonstrate that EGC preferentially reduced the activation of JNK/SAPK (stress-activated protein kinase) signal transduction pathway. 8. It is suggested that the antiproliferative effect of epigallocatechin on vascular smooth muscle cells may partly be mediated through inhibition of protein tyrosine kinase activity, reducing c-jun mRNA expression and inhibiting JNK1 activation. Tea catechins may be useful as a template for the development of drugs to prevent the pathological changes of atherosclerosis and post-angioplasty restenosis.
Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Catechin/analogs & derivatives , Flavonoids/pharmacology , Genes, jun , Mitogen-Activated Protein Kinases , Muscle, Smooth, Vascular/drug effects , Animals , Cell Division/drug effects , Cells, Cultured , Enzyme Inhibitors/pharmacology , Gene Expression Regulation/drug effects , Genes, fos , Genes, myc , Humans , JNK Mitogen-Activated Protein Kinases , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/enzymology , Phosphorylation , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rabbits , Rats , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , TeaABSTRACT
1. The possible mechanisms of the antiproliferative effect of polyhydroxylated fullerene (fullerenol), a novel free radical trapper, were studied in rat vascular smooth muscle cells (A7r5 cells) and compared with the effect of ascorbic acid. 2. Fullerenol-1 and ascorbic acid inhibited the proliferative responses in a number of cells, including rat aortic smooth muscle cells (A7r5 cells), human coronary artery smooth muscle cells, and human CEM lymphocytes (CEM cells) in a concentration dependent manner. 3. At the concentration range of 10(-6) to 10(-2) M, fullerenol-1 and ascorbic acid concentration-dependently inhibited the proliferative responses stimulated by serum in A7r5 cells. Fullerenol-1 was more potent than ascorbic acid. 4. The production of O2- induced by alloxan, a diabetogenic compound, was reduced by fullerenol-1 (10(-4) M) in the presence of A7r5 cells. 5. The cytosolic protein kinase C activity of A7r5 cells stimulated by phorbol ester was reduced by 10(-3) M fullerenol-1, but not ascorbic acid (10(-4)-10(-2) M) and fullerenol-1 at lower concentrations (10(-6)-10(-4) M). 6. In contrast, the membraneous protein tyrosine kinase activity of A7r5 cells stimulated by foetal calf serum was significantly reduced by fullerenol-1 (10(-6)-10(-3) M) and ascorbic acid (10(-4)-10(-2) M). Again, the inhibitory activity of fullerenol-1 was greater than that of ascorbic acid. 7. Our results demonstrate that fullerenol-1 and ascorbic acid exhibit inhibitory effects on transduction signals in addition to their antioxidative property. It is suggested that the antiproliferative effect of fullerenol-1 on vascular smooth muscle cells may partly be mediated through the inhibition of protein tyrosine kinase.
Subject(s)
Carbon/pharmacology , Fullerenes , Muscle, Smooth, Vascular/drug effects , Animals , Ascorbic Acid/pharmacology , Cell Division/drug effects , Cell Line , Enzyme Activation , Humans , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/enzymology , Protein Kinase C/metabolism , Protein-Tyrosine Kinases/metabolism , Rats , Superoxides/metabolismABSTRACT
Feinberg et al. proposed that right-hemisphere-damaged stroke patients with anosognosia for hemiplegia (AHP) confabulate seeing stimuli on the left side but those without AHP admit to having inadequate visual information. This study examines the relationship between AHP and confabulation using selective anesthesia of the cerebral hemispheres. Seventeen patients with intractable epilepsy were tested during intracarotid methohexital infusion. For half of the trials, subjects were stimulated on their paretic hand with a material (sandpaper, metal, or cloth), and for the remaining trials they were not stimulated. The subjects were trained to use a pointing response to indicate if they been stimulated and the type of material they had felt. Admission of uncertainty was defined as pointing to a question mark. Confabulation was defined as any material response to a no-touch trial. During anesthesia of either hemisphere, subjects with and without AHP confabulated responses. The AHP and non-AHP groups did not differ in admission of uncertainty. Our results support the postulate that confabulation and AHP are independent disorders, and therefore confabulation cannot fully account for AHP.
Subject(s)
Agnosia/physiopathology , Fantasy , Memory Disorders/physiopathology , Reality Testing , Adolescent , Adult , Aged , Agnosia/psychology , Anesthetics, Intravenous , Carotid Arteries , Dominance, Cerebral/physiology , Epilepsy/diagnosis , Epilepsy/physiopathology , Epilepsy/psychology , Female , Humans , Injections, Intra-Arterial , Male , Memory Disorders/psychology , Methohexital , Middle Aged , Neuropsychological Tests , Verbal Behavior/physiologyABSTRACT
Heregulins bind directly to ErbB3 and ErbB4 receptors, leading to multiple dimerization possibilities including heterodimerization with the ErbB2 receptor. We have generated ErbB3-, ErbB2- and heregulin-deficient mice to assess their roles in development and differentiation. Heregulin(-/-) and ErbB2(-/-) embryos died on E10.5 due to a lack of cardiac ventricular myocyte differentiation; ErbB3(-/-) embryos survived until E13.5 exhibiting cardiac cushion abnormalities leading to blood reflux through defective valves. In ErbB3(-/-) embryos, the midbrain/hindbrain region was strikingly affected, with little differentiation of the cerebellar plate. Cranial ganglia defects, while present in all three nulls, were less severe in ErbB3(-/-) embryos. The cranial ganglia defects, along with a dramatic reduction in Schwann cells, enteric ganglia and adrenal chromaffin cells, suggests a generalized effect on the neural crest. Numerous organs, including the stomach and pancreas also exhibited anomalous development.
Subject(s)
Cerebellum/embryology , ErbB Receptors/physiology , Glycoproteins/physiology , Heart/embryology , Proto-Oncogene Proteins/physiology , Receptor, ErbB-2/physiology , Transcription Factors , Zebrafish Proteins , Adrenal Glands/embryology , Amino Acid Sequence , Animals , Cell Differentiation , Epithelium/embryology , Ganglia/embryology , Gene Expression Regulation, Developmental , Gene Targeting , Glycoproteins/genetics , Homeodomain Proteins/analysis , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Pancreas/embryology , Proto-Oncogene Proteins/genetics , RNA, Messenger/analysis , Rats , Receptor, ErbB-3 , Stomach/embryology , Wnt ProteinsABSTRACT
UNLABELLED: Hemostasis (HS) in 134 healthy subjects of over 20 years old was investigated. The cases with HS symptom were 45.5%, which increased with age. TXB2, 6-keto-PGF1 alpha and T/K ratio were measured by radioimmuno assay (RIA). RESULTS: elevation of TXB2 was more significant in the middle age and old age than in the young group (P < 0.01). But the level of 6-keto-PGF1 alpha in various age group didn't changed significantly; while the ratio between TXB2 and 6-keto-PGF1 alpha was more significant in the aged than in the young person (P < 0.01). The results revealed that there was hypercoagulable tendency with the increase of age, and it was correlated with TXB2 and 6-keto-PGF1 alpha. It is significant in theory and practice to prevent and cure the cardiovascular and cerebrovascular disease as well as HS with the traditional Chinese medicine.
Subject(s)
6-Ketoprostaglandin F1 alpha/blood , Hemostasis , Medicine, Chinese Traditional , Thromboxane B2/blood , Adult , Age Factors , Aged , Aged, 80 and over , Blood Coagulation , Blood Viscosity , Female , Humans , Male , Middle Aged , SyndromeABSTRACT
Insulin-like growth factor-I (IGF-I) modulates renal function, growth, and repair. IGF-I produced in the kidney is one component of the intrarenal IGF-I system comprising the IGF-I receptor (IGF-IR) and six IGF-binding proteins (IGFBP). Because of the physiologic importance of IGF-I and its potential therapeutic properties, the renal sites of mRNA synthesis for IGF-I, IGF-IR, and IGFBP-I through IGFBP-5 were characterized in rat kidney by in situ hybridization. Anatomical heterogeneity was prominent. IGF-I mRNA was present in the thick ascending limb of Henle in the outer medulla, whereas IGF-IR mRNA was diffusely present at low levels throughout the kidney. IGFBP-I mRNA was localized to cells within the distal convoluted tubules as well as the thick ascending limb of Henle. IGFBP-2 mRNA was expressed in glomeruli, medullary ray collecting ducts, pelvic smooth muscle and uroepithelium, and the papilla tip; IGFBP-3 mRNA was localized to the cortical interstitium, whereas IGFBP-4 mRNA was expressed in proximal tubules, medullary ray collecting ducts, and glomeruli. IGFBP-5 was strongly positive throughout the medulla with lesser expression in the distal convoluted tubules and glomeruli. This study highlights the complexity of the intrarenal IGF-I system. The striking heterogeneity of IGFBP gene expression suggests that the various IGFBP may have diverse modulatory effects on the action of IGF-I or discrete effects of their own.