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1.
Jpn J Radiol ; 42(2): 201-207, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37792149

ABSTRACT

PURPOSE: Herein, we assessed the accuracy of large language models (LLMs) in generating responses to questions in clinical radiology practice. We compared the performance of ChatGPT, GPT-4, and Google Bard using questions from the Japan Radiology Board Examination (JRBE). MATERIALS AND METHODS: In total, 103 questions from the JRBE 2022 were used with permission from the Japan Radiological Society. These questions were categorized by pattern, required level of thinking, and topic. McNemar's test was used to compare the proportion of correct responses between the LLMs. Fisher's exact test was used to assess the performance of GPT-4 for each topic category. RESULTS: ChatGPT, GPT-4, and Google Bard correctly answered 40.8% (42 of 103), 65.0% (67 of 103), and 38.8% (40 of 103) of the questions, respectively. GPT-4 significantly outperformed ChatGPT by 24.2% (p < 0.001) and Google Bard by 26.2% (p < 0.001). In the categorical analysis by level of thinking, GPT-4 correctly answered 79.7% of the lower-order questions, which was significantly higher than ChatGPT or Google Bard (p < 0.001). The categorical analysis by question pattern revealed GPT-4's superiority over ChatGPT (67.4% vs. 46.5%, p = 0.004) and Google Bard (39.5%, p < 0.001) in the single-answer questions. The categorical analysis by topic revealed that GPT-4 outperformed ChatGPT (40%, p = 0.013) and Google Bard (26.7%, p = 0.004). No significant differences were observed between the LLMs in the categories not mentioned above. The performance of GPT-4 was significantly better in nuclear medicine (93.3%) than in diagnostic radiology (55.8%; p < 0.001). GPT-4 also performed better on lower-order questions than on higher-order questions (79.7% vs. 45.5%, p < 0.001). CONCLUSION: ChatGPTplus based on GPT-4 scored 65% when answering Japanese questions from the JRBE, outperforming ChatGPT and Google Bard. This highlights the potential of using LLMs to address advanced clinical questions in the field of radiology in Japan.


Subject(s)
Nuclear Medicine , Humans , Japan , Radiography
2.
Cardiovasc Intervent Radiol ; 46(12): 1666-1673, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37973663

ABSTRACT

PURPOSE: To describe a novel technique of transvenous radiofrequency catheter ablation of an aldosterone-producing adenoma (APA) of the left adrenal gland using the GOS System (Japan Lifeline, Tokyo, Japan). Using the GOS system, a flexible radiofrequency tip catheter can be inserted into the adrenal central and tributary veins, the drainers for functional tumors. MATERIALS AND METHODS: An APA at the left adrenal gland, which was diagnosed by segmental adrenal venous sampling following administration of 0.25 mg cosyntropin, was ablated using the GOS catheter inserted into adrenal tributary veins via a right femoral vein 7-Fr sheath. The effect of radiofrequency ablation on APA was assessed using the international consensus on surgical outcomes for unilateral primary aldosteronism (PA). RESULTS: No device-related complications were observed. The patient was deeply sedated under blood pressure and heart rate control with continuous administration of ß-blockers. Then, the tumor and surrounding adrenal gland were cauterized at 7000 J two times each in sequence. The output time was 7-11 min for each ablation and 80 min in total. For blood pressure and pulse rate control, esmolol hydrochloride and phentolamine mesylate were used. The contrast enhancement of APA disappeared on dynamic CT immediately after the procedure. PA was biochemically cured until 12 months after the procedure. CONCLUSION: Using the radiofrequency device with the GOS catheter and system is a method for cauterizing adrenal tumors from blood vessels. This approach resulted in a marked reduction in aldosterone concentrations and a complete biochemical cure of PA over the observation period.


Subject(s)
Adrenal Gland Neoplasms , Catheter Ablation , Hyperaldosteronism , Humans , Aldosterone , Adrenal Glands/diagnostic imaging , Adrenal Glands/surgery , Adrenal Glands/blood supply , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/surgery , Catheters/adverse effects , Catheter Ablation/methods , Hyperaldosteronism/etiology , Hyperaldosteronism/surgery , Hyperaldosteronism/diagnosis
3.
Sci Rep ; 12(1): 14090, 2022 08 18.
Article in English | MEDLINE | ID: mdl-35982148

ABSTRACT

Evaluation of feasibility and safety of percutaneous radiofrequency ablation using bipolar radiofrequency devices in a prospective multicenter cohort of patients with benign aldosterone-producing adenoma. A total of five institutions participated. CT-guided percutaneous RFA was performed for patients diagnosed as APA. The safety of the procedure was evaluated using the Common Terminology Criteria for Adverse Events. During the 84-day follow-up period, serial changes in plasma aldosterone concentration and plasma renin activity were measured. The percentage of patients with normalized hormonal activity after the procedure, was calculated with 95% confidence intervals. Forty patients were enrolled, and two patients were excluded for cerebral hemorrhage and no safe puncture root. In another patients, RFA was tried, but an intraprocedural intercostal arterial injury occurred. Consequently, RFA was completed in thirty-seven patients (20 men, 17 women; mean age, 50.4 ± 10.0 year). The tumor size was 14.8 ± 3.8 mm. The treatment success rate of the ablation was 94.6% (35/37), and a 2nd session was performed in 2.7% (1/37) patients. Grade 4 adverse events were observed in 4 out of 38 sessions (10.5%). The normalization of plasma aldosterone concentration or aldosterone-renin ratio was 86.5% (72.0-94.1: 95% confidence interval) on day 84. Percutaneous CT-guided RFA for APA using a bipolar radiofrequency system was safe and feasible with clinical success rate of 86.5% on day 84.


Subject(s)
Adenoma , Catheter Ablation , Radiofrequency Ablation , Adenoma/etiology , Adenoma/surgery , Adult , Aldosterone , Catheter Ablation/adverse effects , Catheter Ablation/methods , Electrodes , Feasibility Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Radiofrequency Ablation/adverse effects , Radiofrequency Ablation/methods , Renin , Tomography, X-Ray Computed , Treatment Outcome
4.
Int J Surg Case Rep ; 60: 164-167, 2019.
Article in English | MEDLINE | ID: mdl-31229769

ABSTRACT

INTRODUCTION: Bochdalek hernia (BH) is a congenital diaphragmatic hernia that generally occurs in infants and is rarely seen in adults. Surgical repair of BH is recommended, but the approach for repairing BH should be selected carefully in individual cases. It is well known that hand-assisted laparoscopic surgery (HALS) has the advantage of preserving tactile sensation compared with standard laparoscopic surgery. We describe an adult patient with a history of abdominal incisional hernia who developed BH that was treated safely by HALS. PRESENTATION OF CASE: An 87-year-old woman was admitted to our hospital with nausea. She had a history of right hemicolectomy and repair of an abdominal incisional hernia using mesh at 5 years after hemicolectomy. Chest and abdominal computed tomography revealed herniation of the gastric corpus through the left posterior diaphragm. BH was diagnosed and hernia repair by HALS was selected as the approach because dense adhesions were expected in the abdominal cavity. The operation was performed safely and her postoperative course was uneventful. CONCLUSION: HALS was useful, especially when removing adhesions around the hernial orifice. HALS is a feasible approach for BH and should be considered as one of the options in patients with a history of previous abdominal surgery.

5.
Kurume Med J ; 65(1): 17-21, 2018 Dec 21.
Article in English | MEDLINE | ID: mdl-30158359

ABSTRACT

Cerebral air embolism following central venous catheter (CVC) removal is extremely rare. We report a case of cerebral air embolism with loss of consciousness after removal of CVC caused by pulmonary arteriovenous malformation (PAVM). Computed tomography revealed air bubbles in the internal carotid arteries along the sulci in the cerebral hemispheres, as well as a PAVM. The cerebral air embolism was treated with hyperbaric oxygen and intravenous thrombolytic therapy, and transcatheter embolization of the PAVM was performed. When inserting/removing CVC in a patient with a small PAVM, treatment of the PAVM, irrespective of its size, could prevent the type of complication that occurred in our present case.


Subject(s)
Arteriovenous Malformations/complications , Catheterization, Central Venous/instrumentation , Catheters, Indwelling , Central Venous Catheters , Device Removal/adverse effects , Embolism, Air/etiology , Intracranial Embolism/etiology , Pulmonary Artery/abnormalities , Pulmonary Veins/abnormalities , Arteriovenous Malformations/diagnostic imaging , Arteriovenous Malformations/therapy , Computed Tomography Angiography , Embolism, Air/diagnostic imaging , Embolism, Air/drug therapy , Embolization, Therapeutic , Female , Humans , Hyperbaric Oxygenation , Intracranial Embolism/diagnostic imaging , Intracranial Embolism/drug therapy , Middle Aged , Pulmonary Artery/diagnostic imaging , Pulmonary Veins/diagnostic imaging , Thrombolytic Therapy
6.
Eur Radiol ; 26(3): 622-30, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26108640

ABSTRACT

OBJECTIVES: To evaluate visualization of the right adrenal vein (RAV) with multidetector CT and non-contrast-enhanced MR imaging in patients with primary aldosteronism. METHODS: A total of 125 patients (67 men) scheduled for adrenal venous sampling (AVS) were included. Dynamic 64-detector-row CT and balanced steady-state free precession-based non-contrast-enhanced 3-T MR imaging were performed. RAV visualization based on a four-point score was documented. Both anatomical location and variation on cross-sectional imaging were evaluated, and the findings were compared with catheter venography as the gold standard. RESULTS: The RAV was visualized in 93.2% by CT and 84.8% by MR imaging (p = 0.02). Positive predictive values of RAV visualization were 100% for CT and 95.2% for MR imaging. Imaging score was significantly higher in CT than MR imaging (p < 0.01). The RAV formed a common trunk with an accessory hepatic vein in 16% of patients. The RAV orifice level on cross-sectional imaging was concordant with catheter venography within the range of 1/3 vertebral height in >70% of subjects. Success rate of AVS was 99.2%. CONCLUSIONS: Dynamic CT is a reliable way to map the RAV prior to AVS. Non-contrast-enhanced MR imaging is an alternative when there is a risk of complication from contrast media or radiation exposure. KEY POINTS: Dynamic CT and non-contrast-enhanced MR imaging detect the right adrenal vein (RAV). Dynamic CT can visualize the RAV more than non-contrast-enhanced MR imaging. Mapping the RAV helps to achieve successful adrenal venous sampling. Sixteen per cent of RAVs share the common trunk with accessory hepatic veins.


Subject(s)
Adrenal Glands/blood supply , Hyperaldosteronism/diagnostic imaging , Magnetic Resonance Angiography/methods , Multidetector Computed Tomography/methods , Multimodal Imaging/methods , Phlebography/methods , Adrenal Glands/diagnostic imaging , Adult , Aged , Anatomic Variation , Anatomy, Cross-Sectional/methods , Catheterization, Peripheral/methods , Contrast Media , Female , Hepatic Veins/diagnostic imaging , Humans , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Angiography/statistics & numerical data , Male , Middle Aged , Multidetector Computed Tomography/statistics & numerical data , Multimodal Imaging/statistics & numerical data , Phlebography/instrumentation , Predictive Value of Tests , Vena Cava, Inferior/diagnostic imaging
9.
J Sports Sci ; 31(16): 1841-53, 2013.
Article in English | MEDLINE | ID: mdl-23879798

ABSTRACT

The purpose of the present study was to relate 3D acceleration patterns of the lower and upper trunk during running to running gait cycle, assess the validity of stride duration estimated from acceleration patterns, investigate speed-dependent changes in acceleration, and examine the test-retest reliability of these parameters. Thirteen healthy young men performed two running trials each on a treadmill and on land at three speeds (slow, preferred, and fast). The 3D accelerations were measured at the L3 spinous process (lower trunk) and the ensiform process (upper trunk) and synchronised with digital video data. The amplitude and root mean square of acceleration and stride duration were calculated and then analysed by three-way analysis of variance to test effects of running conditions, device location, and running speed. Bland-Altman analysis was used to evaluate the test-retest reliability. Marked changes in acceleration were observed in relation to foot strike during running. Stride durations calculated from the vertical accelerations were nearly equal to those estimated from video data. There were significant speed effects on all parameters, and the low test-retest reliability was confirmed in the anterior-posterior acceleration during treadmill running and the anterior-posterior acceleration at slow speed during treadmill and overground running.


Subject(s)
Acceleration , Running , Task Performance and Analysis , Torso , Adult , Analysis of Variance , Biomechanical Phenomena , Foot , Gait , Humans , Male , Reproducibility of Results , Young Adult
10.
Palliat Med ; 27(3): 284-5, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22661318

ABSTRACT

Persistent hiccup can cause anorexia, weight loss, disabling sleep deprivation, anxiety, and depression. Therefore, relief of persistent hiccup is important for advanced cancer patients and their family. Most reports on this condition are case series reports advocating the use of baclofen, haloperidol, gabapentin, and midazolam. However, these medications are occasionally ineffective or accompanied by intolerable side effects. The sodium channel blocker lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms. Intravenous administration of lidocaine is common but efficacy has also been reported for subcutaneous infusion. In advanced cancer patients, subcutaneous infusion is easy, advantageous, and accompanied by less discomfort. We report a case of severe and sustained hiccup caused by gastric cancer that was successfully treated with a continuous subcutaneous infusion of lidocaine (480 mg (24 ml)/day) without severe side effects.


Subject(s)
Anesthetics, Local/administration & dosage , Hiccup/drug therapy , Lidocaine/administration & dosage , Stomach Neoplasms/complications , Voltage-Gated Sodium Channel Blockers/administration & dosage , Aged, 80 and over , Hiccup/etiology , Humans , Infusions, Subcutaneous , Male , Treatment Outcome
11.
Am J Hosp Palliat Care ; 30(3): 305-11, 2013 May.
Article in English | MEDLINE | ID: mdl-22669937

ABSTRACT

Pain and dyspnea are the most prevalent and distressing symptoms in patients with terminally ill cancer. Evidences have accumulated for the effects of morphine on dyspnea, whereas little is known about the effects of oxycodone on dyspnea. We investigated the effectiveness of oxycodone for dyspnea in patients with terminally ill cancer. The injectable form of compound oxycodone (iOC) containing hydrocotarnine was administered continuously via subcutaneous route. We administered iOC to 136 patients. The effect on dyspnea was less conspicuous than pain, yet iOC was effective for dyspnea with varying degrees. None of the adverse effects observed were serious. These results suggest that continuous subcutaneous administration of oxycodone could be one of the reasonable alternatives in the management of dyspnea in patients with terminally ill cancer.


Subject(s)
Dyspnea/drug therapy , Neoplasms/complications , Oxycodone/therapeutic use , Terminal Care/methods , Aged , Aged, 80 and over , Female , Humans , Infusions, Subcutaneous , Male , Middle Aged , Neoplasms/drug therapy , Oxycodone/administration & dosage , Pain Management/methods , Retrospective Studies , Treatment Outcome
12.
J Pain Symptom Manage ; 44(4): 604-7, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22771132

ABSTRACT

Bowel obstruction is one of the most common complications in patients with advanced cancer. Incomplete bowel obstruction is one of the leading causes of nausea and vomiting, which may result in a substantial impairment to quality of life. We explored the antiemetic activity of olanzapine against nausea and vomiting in cancer patients with incomplete bowel obstruction. This retrospective study was carried out on a palliative care unit, using an electronic medical record from 2007 to 2009. The intensity of the symptom was evaluated and classified from the medical records on four scales. The frequency of vomiting also was noted from the medical records. During this study period, 20 patients met the inclusion criteria. The average dose of olanzapine was 4.9±1.2mg and treatment duration was 23.4±16.2 days. Olanzapine treatment led to a significant decrease in the average intensity score of nausea from 2.4±0.7 to 0.2±0.4 (P<0.001). Of the 20 patients, 18 (90%) experienced a reduction in the intensity of nausea. The average frequency of vomiting significantly decreased after olanzapine treatment from 1.1±1.3 times/day (median 0.5; range 0-4) before the treatment to 0.3±0.5 times/day (median 0; range 0-1) after the treatment (P<0.01). Before the treatment, 10 patients experienced vomiting; eight of these patients experienced a decrease in the frequency of vomiting with olanzapine treatment. Our study suggests the potential efficacy of olanzapine for relief of nausea in incomplete bowel obstruction. A prospective trial is promising.


Subject(s)
Antiemetics/therapeutic use , Benzodiazepines/therapeutic use , Intestinal Obstruction/complications , Nausea/drug therapy , Neoplasms/complications , Vomiting/drug therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Nausea/etiology , Olanzapine , Retrospective Studies , Treatment Outcome , Vomiting/etiology
13.
Gan To Kagaku Ryoho ; 37 Suppl 2: 253-5, 2010 Dec.
Article in Japanese | MEDLINE | ID: mdl-21368541

ABSTRACT

A palliative care team provides palliative care in the hospital setting.However, palliative care might be discontinued when a patient was switched to an outpatient from an inpatient or when a patient was being transferred to another hospital.In the present work, we report a case who could receive anti-cancer therapy and palliative care simultaneously at home.The case is a 46-year-old woman.She was diagnosed as left ovary cancer in 1990's and underwent an operation followed by chemotherapy. The tumor relapsed and invaded the sigmoid colon in 2000's.She then developed an intestinal obstruction and was hospitalized.After her conditions were stabilized, she was discharged but still needed a high degree of medical interventions. She was introduced to another hospital providing a home palliative care as well as emergency admission.She could fulfill her desire to receive a palliative care and chemotherapy simultaneously at home through this seamless healthcare linkage.It should be insisted that hospital oncologists and home doctors need to acquire the knowledge of palliative care and close cooperation between them is required.It is also important to establish a comprehensive healthcare linkage system in the society.


Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Community Networks , Doxorubicin/therapeutic use , Home Care Services , Ovarian Neoplasms/therapy , Palliative Care , Patient Care Team , Female , Humans , Middle Aged , Ovarian Neoplasms/drug therapy
14.
J Biol Chem ; 284(10): 6109-15, 2009 Mar 06.
Article in English | MEDLINE | ID: mdl-19122240

ABSTRACT

Transforming growth factor-beta (TGF-beta) is crucial in numerous cellular processes, such as proliferation, differentiation, migration, and apoptosis. TGF-beta signaling is transduced by intracellular Smad proteins that are regulated by the ubiquitin-proteasome system. Smad ubiquitin regulatory factor 2 (Smurf2) prevents TGF-beta and bone morphogenetic protein signaling by interacting with Smads and inducing their ubiquitin-mediated degradation. Here we identified Pin1, a peptidylprolyl cis-trans isomerase, as a novel protein binding Smads. Pin1 interacted with Smad2 and Smad3 but not Smad4; this interaction was enhanced by the phosphorylation of (S/T)P motifs in the Smad linker region. (S/T)P motif phosphorylation also enhanced the interaction of Smad2/3 with Smurf2. Pin1 reduced Smad2/3 protein levels in a manner dependent on its peptidyl-prolyl cis-trans isomerase activity. Knockdown of Pin1 increased the protein levels of endogenous Smad2/3. In addition, Pin1 both enhanced the interaction of Smurf2 with Smads and enhanced Smad ubiquitination. Pin1 inhibited TGF-beta-induced transcription and gene expression, suggesting that Pin1 negatively regulates TGF-beta signaling by down-regulating Smad2/3 protein levels via induction of Smurf2-mediated ubiquitin-proteasomal degradation.


Subject(s)
Down-Regulation/physiology , Peptidylprolyl Isomerase/metabolism , Signal Transduction/physiology , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Transforming Growth Factor beta/metabolism , Amino Acid Motifs/physiology , Animals , Bone Morphogenetic Proteins/genetics , Bone Morphogenetic Proteins/metabolism , COS Cells , Chlorocebus aethiops , Gene Knockdown Techniques/methods , Humans , NIMA-Interacting Peptidylprolyl Isomerase , Peptidylprolyl Isomerase/genetics , Phosphorylation/physiology , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/metabolism , Protein Binding/physiology , Smad2 Protein/genetics , Smad3 Protein/genetics , Transforming Growth Factor beta/genetics , Ubiquitin/genetics , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism
15.
Gan To Kagaku Ryoho ; 36 Suppl 1: 128-31, 2009 Dec.
Article in Japanese | MEDLINE | ID: mdl-20443425

ABSTRACT

Tokyo Kosei-Nenkin Hospital operates the Tokyo Metropolitan Home Palliative Care Support Center (TMHPCSC) commissioned from the Tokyo metropolitan government. TMHPCSC held one lecture workshop for healthcare professionals and one symposium for general citizens in fiscal year ended March 2008. Questionnaires were distributed to the attendants at the beginning of meetings and collected at the end. Several problems in the present home palliative care system were revealed from the questionnaires. Those include problems associated with palliation skills, cooperation among multiple professionals, especially between medical staff and caring staff, transition from hospital to home and aging of society. These problems should be tackled as issues of the whole society.


Subject(s)
Home Care Services , Palliative Care , Surveys and Questionnaires , Education, Continuing , Patient Care Team , Tokyo
16.
Acta Med Okayama ; 59(1): 1-9, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15902993

ABSTRACT

DNA damage causes chromosomal instability leading to oncogenesis, apoptosis, and severe failure of cell functions. The DNA repair system includes base excision repair, nucleotide excision repair, mismatch repair, translesion replication, non-homologous end-joining, and recombinational repair. Homologous recombination performs the recombinational repair. The RAD51 gene is an ortholog of Esherichia coli recA, and the gene product Rad51 protein plays a central role in the homologous recombination. In mammals, 7 recA-like genes have been identified: RAD51, RAD51L1/B, RAD51L2/C, RAD51L3/D, XRCC2, XRCC3, and DMC1. These genes, with the exception of meiosis-specific DMC1, are essential for development in mammals. Disruption of the RAD51 gene leads to cell death, whereas RAD51L1/B, RAD51L2/C, RAD51L3/D, XRCC2, and XRCC3 genes (RAD51 paralogs) are not essential for viability of cells, but these gene-deficient cells exhibit a similar defective phenotype. Yeast two-hybrid analysis, co-immunoprecipitation, mutation analysis, and domain mapping of Rad51 and Rad51 paralogs have revealed protein-protein interactions among these gene products. Recent investigations have shown that Rad51 paralogs play a role not only in an early step, but also in a late step of homologous recombination. In addition, identification of alternative transcripts of some RAD51 paralogs may reflect the complexity of the homologous recombination system.


Subject(s)
DNA-Binding Proteins/physiology , Mammals/physiology , Multigene Family/physiology , Rec A Recombinases/genetics , Rec A Recombinases/metabolism , Recombination, Genetic/physiology , Animals , Escherichia coli/genetics , Escherichia coli/metabolism , Humans , Rad51 Recombinase
17.
Biochim Biophys Acta ; 1679(2): 107-16, 2004 Aug 12.
Article in English | MEDLINE | ID: mdl-15297144

ABSTRACT

The RecA/RAD51 family plays a central role in DNA recombinational repair. The targeted disruption of mouse RAD51L3/TRAD is lethal during embryogenesis, suggesting that this protein is essential for development. Recently, we reported multiple alternative splice variants of human RAD51L3/TRAD transcripts. In this study, we have identified multiple mouse transcript variants. Complete sequence analysis of the genomic and cDNA clones has confirmed that the exon-intron structures obey the GT/AG splicing rule, and that the multiplicity of the transcripts is due to alternative splicing. In addition, we have determined the transcription initiation site by rapid amplification of cDNA 5'-end (5'-RACE). These results show that the mouse gene structure is very similar to that of humans.


Subject(s)
Alternative Splicing , DNA-Binding Proteins/genetics , Rec A Recombinases/genetics , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , DNA, Complementary/biosynthesis , DNA, Complementary/chemistry , Exons , Mice , Molecular Sequence Data , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis , Transcription Initiation Site
19.
Acta Med Okayama ; 58(6): 263-70, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15762294

ABSTRACT

Because of the many superficial similarities between the immune system and the central nervous system, it has long been speculated that somatic DNA recombination is, like the immune system, involved in brain development and function. To examine whether or not the V(D)J recombination signals of the immune system work in an in vitro neural differentiation model, the P19 mouse embryonal carcinoma cell line was transfected with a reporter gene that is designed, when rearranged, to express bacterial beta-galactosidase, which was previously reported to exhibit somatic DNA recombination in the transgenic mouse brain. The cloned cells were then induced into neural cells by retinoic acid treatment. This neural induction treatment resulted in the cloning of a P19 cell line that showed a high incidence of beta-galactosidase-positive cells. Most of these beta-galactosidase-positive cells were immunocytochemically identified as either neurons, neuroepithelial cells, or astrocytes. The 5'-end sequences of the beta-galactosidase transcripts expressed in the induced cells were analyzed, and sequences were found that seemed to reflect DNA rearrangement through re-integration of the reporter gene into the host genome. However, the V(D)J recombination signals did not work in the in vitro model. These results suggested that DNA rearrangement activity though integration increased during neural differentiation of P19 cells.


Subject(s)
Cell Differentiation/physiology , Gene Rearrangement , Neoplastic Stem Cells/physiology , Neurons/cytology , Neurons/drug effects , Tretinoin/pharmacology , Animals , Base Sequence , Cell Line, Tumor , Embryonal Carcinoma Stem Cells , Genes, Reporter , Mice , Mice, Transgenic , Molecular Sequence Data , Neoplastic Stem Cells/cytology , Neurons/physiology , beta-Galactosidase/genetics , beta-Galactosidase/metabolism
20.
Cancer Res ; 62(20): 5955-61, 2002 Oct 15.
Article in English | MEDLINE | ID: mdl-12384562

ABSTRACT

Smad2 is a receptor-regulated Smad that is activated specifically by transforming growth factor beta and activin signaling. We disrupted the mouse Smad2 gene by gene targeting. Homozygous Smad2 mutant mice died around E8.5 with impaired visceral endoderm function and deficiency of mesoderm formation. Heterozygotes were fertile and had no apparent abnormality up to at least 1 1/2 year of age. To examine the role of Smad2 inactivation in the process of carcinogenesis, we prepared compound heterozygous mice, which carry both Apc and Smad2 mutations on the same chromosome in the cis-configuration. Compound inactivation of Smad2 in heterozygous Apc mutant mice did not change the total number of intestinal tumors but increased sudden death from intestinal obstruction caused by extremely large tumors. Furthermore, histological examination revealed that Apc/Smad2 cis-compound heterozygotes developed multiple invasive cancers that had never been observed in Apc single heterozygotes. These results indicate that loss of Smad2 does not initiate tumorigenesis by itself but accelerates malignant progression of tumors to invasive cancer in the late stages of carcinogenesis.


Subject(s)
DNA-Binding Proteins/genetics , Genes, APC , Intestinal Neoplasms/genetics , Intestinal Neoplasms/pathology , Trans-Activators/genetics , Animals , DNA-Binding Proteins/deficiency , Disease Progression , Female , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mutation , Smad2 Protein , Trans-Activators/deficiency
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