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1.
Surg Endosc ; 33(6): 1769-1776, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30291444

RESUMO

BACKGROUND: The number of colorectal cancer cases is increasing, and so the number of laparoscopic colectomy procedures being performed is also increasing, leading to an increased workload for surgeons. However, operating for prolonged time periods may cause surgeons to lose their concentration and develop fatigue. We hypothesized that there is a time-of-day variation in outcome for patients with colorectal cancer who undergo laparoscopic colectomy. The present study aimed to compare the operative outcome between laparoscopic colectomy for colorectal cancer performed in the morning versus the afternoon. METHODS: This was a single-center, retrospective study. All 1961 consecutive patients who underwent laparoscopic surgery for colorectal cancer between 2007 and 2017 were included; 1006 of these patients underwent morning surgery, while 955 underwent afternoon surgery. These patients were analyzed using propensity score matching, giving 791 patients in each group. The short- and long-term outcomes in both groups were compared. RESULTS: Before propensity score matching, the morning group had a larger mean tumor size than the afternoon group (30 cm vs 35 cm; P = 0.0035). After matching, the two groups did not significantly differ in any patient characteristics. Compared with the afternoon group, the morning group had a significantly lesser incidence of intra-operative organ injury (0.25% vs 1.13%; P = 0.027), and a significantly greater incidence of post-operative abdominal abscess (2.03% vs 0.75% P = 0.028). The incidences of other complications and morbidities were similar in both groups. The median operative time in the morning group (201 min) was significantly longer than that in the afternoon group (193 min; P = 0.0124). The two groups did not differ in 5-year overall survival rates and 5-year disease-free rates within any disease stage. CONCLUSIONS: Surgical start times are correlated with surgical outcomes. Our data will help to ensure the safest possible surgeries.


Assuntos
Neoplasias Colorretais/cirurgia , Duração da Cirurgia , Idoso , Idoso de 80 Anos ou mais , Colectomia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Análise de Sobrevida
2.
Vox Sang ; 113(2): 128-135, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29067694

RESUMO

BACKGROUND AND OBJECTIVES: Adverse reactions to platelet transfusions are a problem. Children with primary haematological and malignant diseases may experience allergic transfusion reactions (ATRs) to platelet concentrates (PCs), which can be prevented by giving washed PCs. A new platelet additive solution, using bicarbonated Ringer's solution and acid-citrate-dextrose formula A (BRS-A), may be better for platelet washing and storage, but clinical data are scarce. MATERIALS AND METHODS: A retrospective cohort study for consecutive cases was performed between 2013 and 2017. For 24 months, we transfused washed PCs containing BRS-A to children with primary haematological and malignant diseases and previous adverse reactions. Patients transfused with conventional PCs (containing residual plasma) were assigned as controls, and results were compared in terms of frequency of ATRs, corrected count increment (CCI) and occurrence of bleeding. We also studied children transfused with PCs washed by a different system as historical controls. RESULTS: Thirty-two patients received 377 conventional PC transfusions. ATRs occurred in 12 (37·5%) patients from transfused with 18 (4·8%) bags. Thirteen patients, who experienced reactions to regular PCs in plasma, then received 119 transfusion bags of washed PCs containing BRS-A, and none had ATRs to washed PCs containing BRS-A. Before study period, six patients transfused 137 classical washed PCs with different platelet additive solution, under same indication, ATRs occurred in one (16·7%) patient from transfused with one (0·7%) bags. CCIs (24 h) in were lower with classical washed PCs (1·26 ± 0·54) compared to regular PCs in plasma (2·07 ± 0·76) (P < 0·001), but there was no difference between washed PCs containing BRS-A (2·14 ± 0·77) and regular PCs (2·21 ± 0·79) (P = 0·769), and we saw no post-transfusion bleeding. CONCLUSION: Washed PCs containing BRS-A appear to prevent ATRs without loss of transfusion efficacy in children with primary haematological and malignant diseases. Their efficacy should be further evaluated through larger prospective clinical trials.


Assuntos
Plaquetas/imunologia , Transfusão de Plaquetas/métodos , Reação Transfusional/prevenção & controle , Plaquetas/efeitos dos fármacos , Criança , Feminino , Humanos , Soluções Isotônicas/farmacologia , Masculino , Transfusão de Plaquetas/efeitos adversos , Reação Transfusional/imunologia
3.
Vox Sang ; 110(4): 376-84, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26808840

RESUMO

BACKGROUND AND OBJECTIVES: Allergic transfusion reactions (ATRs) and febrile non-haemolytic transfusion reactions (FNHTRs) are the two major types of transfusion-related adverse reactions (TRARs). Although prestorage leucocyte reduction and diversion of the first aliquot of blood (LR/D) could reduce FNHTRs and bacterial contamination in adult transfusion, ATRs are still problematic. In addition, there is little information about TRARs in paediatric population. MATERIALS AND METHODS: We conducted a single-centre retrospective analysis of all transfusions, except washing products, and TRARs for 153 months to evaluate related factors such as delivery of treatment and the characteristics of recipients. RESULTS: Most TRARs were FNHTRs and/or ATRs in children. In delivering blood products with LR/D, the frequencies of not only FNHTRs but also ATRs were significantly reduced with both platelet concentrates (PCs) and red cell concentrates (RCCs). TRARs of fresh-frozen plasma were infrequent in children. In addition, even after the introduction of LR/D, ATRs were significantly more frequent in patients with primary haematological and malignant diseases who received PCs and RCCs, older patients who received PCs and patients who received frequent RCCs. CONCLUSION: These results suggest that leucocytes or mediators from leucocytes are underlying cause of ATRs in addition to FNHTRs in children. Furthermore, particular characteristics of patients would be other risk factors for ATRs.


Assuntos
Hipersensibilidade/etiologia , Reação Transfusional/etiologia , Criança , Pré-Escolar , Transfusão de Eritrócitos/efeitos adversos , Feminino , Humanos , Lactente , Leucócitos/citologia , Masculino , Análise Multivariada , Plasma/química , Transfusão de Plaquetas/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
4.
Eur J Med Res ; 13(3): 133-5, 2008 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-18499560

RESUMO

Bacteremia due to Capnocytophaga sputigena occurred in a 4-year and 9-month-old Japanese girl patient with acute erythroblastic leukemia in Shinshu University Hospital, Japan. On her admission to the hospital, she had a temperature of 38.2 degrees C with canker sore. Prior to the commencement of chemotherapy, peripheral blood culture was carried out with the BacT/Alert 3D System ver. 4.00D (bioMerieux Japan Ltd., Tokyo, Japan) using both the PF and the SN bottles. At 48 hrs of incubation, the System showed the positive sign only in the anaerobic SN bottle for bacterial growth. The strain isolated from the SN bottle was morphologically, biochemically, and genetically characterized, and finally identified as Capnocytophaga sputigena. The causative Capnocytophaga sputigena isolate was found to be a beta-lactamase-producer demonstrating to possess cfxA3 gene. The gene responsible for the production of CfxA3-beta-lactamase was proved to be chromosome-encoded, by means of southern hybridization analysis. This was the first case of bacteremia caused by chromosome-encoded CfxA3-beta-lactamase-producing Capnocytophaga sputigena.


Assuntos
Bacteriemia/microbiologia , Capnocytophaga/isolamento & purificação , Cromossomos Bacterianos , Leucemia Eritroblástica Aguda/complicações , beta-Lactamases/biossíntese , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/complicações , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Capnocytophaga/efeitos dos fármacos , Capnocytophaga/enzimologia , Pré-Escolar , Feminino , Humanos , Testes de Sensibilidade Microbiana , beta-Lactamases/genética
5.
Leukemia ; 20(3): 485-90, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16424864

RESUMO

Among 11 JMML children, two had an abnormal karyotype, and nine had a normal karyotype at onset. In one patient with trisomy 8 and four patients with a normal karyotype, a new clone with an aberrant karyotype emerged 1-14 months after 6-mercaptopurine (6-MP) therapy as shown by G-banding analyses. Fluorescence in situ hybridization disclosed that an abnormal clone existed in approximately 3-6% of bone marrow cells at onset or before 6-MP therapy in all the four cases examined, and increased to approximately 12-90% during the treatment. In culture with granulocyte-macrophage colony-stimulating factor, cytogenetically abnormal clones that proliferated during 6-MP therapy possessed significantly less sensitivity to the antimetabolite, compared with cells that decreased in numbers after the therapy. A PTPN11 mutation was detected in all of granulocyte-macrophage colonies irrespective of karyotypic aberration in one patient, whereas approximately 80% of erythroid colonies and 20% of mixed colonies possessed neither a PTPN11 mutation nor chromosomal abnormalities. The appearance of chromosomal aberrations shown by G-banding during 6-MP therapy in some JMML cases may result, in part, from the growth of a 6-MP-refractory clone that already exists at onset. It is possible that treatment with 6-MP promotes progression of the disease.


Assuntos
Antineoplásicos/uso terapêutico , Aberrações Cromossômicas , Leucemia Mielomonocítica Aguda/tratamento farmacológico , Leucemia Mielomonocítica Aguda/genética , Mercaptopurina/uso terapêutico , Bandeamento Cromossômico , Genes ras , Humanos , Hibridização in Situ Fluorescente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Leucemia Mielomonocítica Aguda/patologia , Mutação , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Proteínas Tirosina Fosfatases/genética
6.
Cancer Res ; 60(3): 522-4, 2000 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-10676628

RESUMO

The frequency of K-ras mutation in biliary duct carcinomas in different locations and the relationship to the form of the junction of the pancreaticobiliary duct (JPBD) are not understood clearly. These points were investigated in the present study. Thirty-seven biliary duct carcinomas in patients without anomalous JPBD were investigated for K-ras mutations. Regarding location, 12 were hilar, 4 in the upper, 11 in the middle, and 10 in the lower portion of the duct. Furthermore, with 14 cases for which the form of the JPBD could be confirmed by endoscopic retrograde cholangiopancreatography or postoperative cholangiopancreatography, division was made into two types: those with a long common channel (>5 mm) in the papilla of Vater (type 1, n = 4), and the other with a shorter or nonapparent common channel (type 2, n = 10). The overall frequency of K-ras mutation was 30%, the incidence gradually increasing from upper to lower regions. K-ras mutations were significantly more frequent in biliary duct carcinomas associated with long common channels (P < 0.05). These results suggest that a long common channel may bear a relation to K-ras mutations in biliary duct carcinogenesis, presumably through its influence on pancreatic juice regurgitation.


Assuntos
Neoplasias dos Ductos Biliares/genética , Ductos Biliares/anormalidades , Genes ras , Mutação , Ductos Pancreáticos/anormalidades , Humanos
7.
Transplant Proc ; 48(4): 1083-6, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320563

RESUMO

BACKGROUND: In this study, we demonstrated our new device for open donor liver surgery with left-sided heptectomy by use of the real-time moving windows (RTMW) method with 8-cm transverse skin incision for living donors from the viewpoints of cosmetic, economic, and safety procedures. METHODS: After the upper abdominal 8-cm transverse skin incision was made, the subcutaneous area was exfoliated and the reverse T-shaped-abdominal incision was made, as in open surgery. After that, the 2 Kent hooks for the upper region and the 2 surgical arms for the lower region were placed. The operative fields of hepatic vein, hepatic hilus, and common hepatic artery were explored, respectively, by use of the RTMW method with the use of the 4 surgical hooks. Hepatic parenchymal dissection was carried out with the use of CUSA and laparosonic coagulating shears. Manipulations of 3 hepatic vessels and the hepatic duct were done by the usual procedure of open surgery. RESULTS: This operative procedure could be performed without laparoscopic techniques. The operative time was 7 hours, without blood transfusion. The operative course was uneventful, and the patient was discharged on postoperative day 11. CONCLUSIONS: Our RTMW method for donor left-sided hepatectomy is considered to be a useful operative procedure from the viewpoints of donor safety, cosmetic advantage, and cost performance.


Assuntos
Dissecação/instrumentação , Hepatectomia/métodos , Transplante de Fígado , Doadores Vivos , Coleta de Tecidos e Órgãos/métodos , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Duração da Cirurgia , Sítio Doador de Transplante
8.
Transplantation ; 69(8): 1645-54, 2000 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-10836376

RESUMO

BACKGROUND: To assess the clinical application of thrombopoietin (TPO) for thrombocytopenia of patients receiving cord blood (CB) or bone marrow (BM) transplants, we examined whether various types of hematopoietic progenitors including megakaryocyte (MK) progenitors from CB and BM exerted different proliferative and differentiative potential in the presence of TPO. METHODS: The development of MK, granulocyte-macrophage, and erythroid/mixed erythroid (E/Mix) progenitors in a serum-deprived liquid culture medium supplemented with TPO was compared between CD34+ CB and BM cells. RESULTS: The CD34+ CB cells generated 30-fold more MKs than the CD34+ BM cells, but the CB-derived MKs were more immature. A single-cell culture study showed that CB CD34+CD38- cells as well as CD34+CD38+ cells proliferated in response to TPO, whereas the two subpopulations of CD34+ BM cells showed little multiplication. In short-term liquid cultures containing CD34+ CB or BM cells, TPO significantly increased the absolute numbers of various types of colony-forming cells, compared with the input values. In particular, MK progenitors and E/Mix progenitors in CB were amplified to a substantially greater extent than in BM. The superior response of CD34+ CB cells to TPO observed in this study may be due in part to the use of cryopreserved cells. CONCLUSIONS: Our results suggest that TPO alone cannot only stimulate megakaryocytopoiesis but also increase the numbers of various types of hematopoietic progenitors, and that quantitative and qualitative differences in TPO-dependent hematopoietic progenitor development exist between CB and BM.


Assuntos
Células da Medula Óssea/fisiologia , Sangue Fetal/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Trombopoetina/fisiologia , Antígenos CD34/análise , Células da Medula Óssea/imunologia , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Senescência Celular , Criopreservação , Sangue Fetal/citologia , Sangue Fetal/imunologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Megacariócitos/citologia , Megacariócitos/fisiologia , Proteínas Recombinantes/farmacologia , Trombopoetina/farmacologia
9.
J Histochem Cytochem ; 49(10): 1269-75, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11561011

RESUMO

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a pyrin N-terminal homology domain (PYD)- and caspase recruitment domain (CARD)-containing a proapoptotic molecule. This molecule has also been identified as a target of methylation-induced silencing (TMS)-1. We cloned the ASC cDNA by immunoscreening using an anti-ASC monoclonal antibody. In this study, we determined the binding site of the anti-ASC monoclonal antibody on ASC and analyzed the expression of ASC in normal human tissues. ASC expression was observed in anterior horn cells of the spinal cord, trophoblasts of the placental villi, tubule epithelium of the kidney, seminiferous tubules and Leydig cells of the testis, hepatocytes and interlobular bile ducts of the liver, squamous epithelial cells of the tonsil and skin, hair follicle, sebaceous and eccrine glands of the skin, and peripheral blood leukocytes. In the colon, ASC was detected in mature epithelial cells facing the luminal side rather than immature cells located deeper in the crypts. These observations indicate that high levels of ASC are abundantly expressed in epithelial cells and leukocytes, which are involved in host defense against external pathogens and in well-differentiated cells, the proliferation of which is regulated.


Assuntos
Apoptose , Caspases/química , Proteínas do Citoesqueleto/metabolismo , Proteínas/química , Animais , Anticorpos Monoclonais , Western Blotting , Proteínas Adaptadoras de Sinalização CARD , Células COS , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/genética , Epitopos , Proteínas de Fluorescência Verde , Humanos , Imuno-Histoquímica , Hibridização In Situ , Proteínas Luminescentes/genética , Microscopia de Fluorescência , Mutação , Especificidade de Órgãos , Estrutura Terciária de Proteína , Pirina , Proteínas Recombinantes de Fusão/metabolismo , Deleção de Sequência , Frações Subcelulares/metabolismo
10.
J Histochem Cytochem ; 49(5): 587-96, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11304796

RESUMO

alpha1,4-N-acetylglucosaminyltransferase (alpha4GnT) is a glycosyltransferase that mediates transfer of GlcNAc to betaGal residues with alpha1,4-linkage, forming GlcNAcalpha1--> 4Galbeta-->R structures. In normal human tissues, glycoproteins having GlcNAcalpha1-->4Galbeta-->R structures at non-reducing terminals are exclusively limited to the mucins secreted from glandular mucous cells of gastric mucosa, Brunner's gland of duodenum, and accessory gland of pancreaticobiliary tract. Recently, we have isolated a cDNA encoding human alpha4GnT by expression cloning. Although alpha4GnT plays a key role in producing this unique glycan in vitro, the actual localization of alpha4GnT was not determined. In this study we examined the localization of alpha4GnT in various human tissues, including gastrointestinal mucosa, using a newly developed antibody against human alpha4GnT. The specificity of the antibody was confirmed by analyses of human gastric adenocarcinoma AGS cells transfected by alpha4GnT cDNA. Expression of alpha4GnT was largely associated with the Golgi region of mucous cells that produce the mucous glycoproteins having GlcNAcalpha1-->4Galbeta-->R, such as the glandular mucous cells of stomach and Brunner's gland. An immunoprecipitation experiment disclosed that two distinct mucin proteins, MUC5AC and MUC6 present in gastric mucin, carried the GlcNAcalpha1-->4Galbeta-->R structures. These results indicate that alpha4GnT is critical to form the mucous glycoproteins having GlcNAcalpha1-->4Galbeta-->R on MUC6 and MUC5AC in vivo.(J Histochem Cytochem 49:587-596, 2001)


Assuntos
Mucosa Gástrica/metabolismo , Mucosa Intestinal/metabolismo , Mucinas/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Animais , Western Blotting , Mucosa Gástrica/enzimologia , Humanos , Imuno-Histoquímica , Mucosa Intestinal/enzimologia , Metaplasia/enzimologia , Metaplasia/metabolismo , Microscopia Confocal , Microscopia Imunoeletrônica , Mucina-5AC , Mucina-6 , Mucinas/química , Especificidade de Órgãos , Testes de Precipitina , Coelhos , Transfecção , Células Tumorais Cultivadas
11.
Am J Med Genet ; 94(4): 265-70, 2000 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-11038437

RESUMO

We report on a Japanese family having an autosomal dominant neurodegenerative disease with chromosomal instability and radiosensitivity. Clinical manifestations of affected members included short stature, osteoporosis, severe dental caries, and various neurological abnormalities, such as mental retardation, depression, dysarthria, hyperreflexia, and ataxic gait. MRI demonstrated a markedly atrophic spinal cord and degeneration of the white matter. Cytogenetic examination showed spontaneous chromosome rearrangements at 14q11.2 and hypersensitivity to radiation and bleomycin. The degree of these cytogenetic abnormalities was significantly higher in the patients than in normal controls but lower than in patients with ataxia telangiectasia or Nijmegen breakage syndrome. Moreover, genetic anticipation was observed in this family: the age of disease onset became earlier, MRI abnormalities more extensive, and the chromosome hypersensitivity to radiation increased in successive generations. We speculate that a basic defect in this family is a mutation in the gene that is responsible for DNA double-strand breakage repair.


Assuntos
Aberrações Cromossômicas/genética , Genes Dominantes , Doenças Neurodegenerativas/genética , Adulto , Feminino , Humanos , Lactente , Japão , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/fisiopatologia , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/fisiopatologia , Linhagem , Recombinação Genética , Síndrome
12.
Hum Pathol ; 31(10): 1223-9, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11070115

RESUMO

To clarify the origin of giant cells in osteoclast-like giant cell tumors (OGCTs) of the pancreas, we performed microscopical, immunohistochemical, and K-ras gene mutation analyses with a microdissection approach in 3 cases, featuring 4 cellular components (osteoclast-like giant cells [OGCs], pleomorphic large cells [PLCs], mononuclear cells, and ductal carcinoma cells). Two cases had abundant OGCs, and 1 case contained large number of both OGCs and PLCs. In each, none of the microdissected OGCs contained any K-ras gene mutation while they were positive for a histiocytic marker (CD-68). In contrast, PLCs, when present, frequently harbored K-ras gene mutations and were negative for CD-68. In all cases, mononuclear cells, a mixture of histiocyte-like and atypical, from microscopic and immunohistochemical viewpoints, also frequently showed K-ras alteration. Histiocyte-like mononuclear cell was equipped with a regular and oval nucleus similar to those in OGCs and was positive for CD-68. Atypical mononuclear cell showed an irregular, pleomorphic, or sometimes bizarre nucleus similar to those in PLCs and was negative for CD-68. All of the K-ras gene mutations found in PLCs and mononuclear cells were the same as in the ductal carcinoma cells within the same tumor. Thus, OGCs differ in origin from ductal cells and are strongly suggested to be nonneoplastic and of mesenchymal origin, whereas PLCs, which harbor K-ras gene mutations, are neoplastic and presumably derived from ductal carcinoma cells. Moreover, mononuclear cells may be classified into 2 types, histiocyte-like and atypical.


Assuntos
Tumores de Células Gigantes/patologia , Células Gigantes/patologia , Osteoclastos/patologia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Análise Mutacional de DNA , Feminino , Genes ras , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade
13.
Hum Pathol ; 31(7): 795-803, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10923915

RESUMO

Mucin-producing tumors (MPTs) of the pancreas accompanied by carcinomas usually include various grades of dysplasia in the ductal epithelium, and invasive areas are histologically similar to those of common invasive ductal carcinomas, suggesting that MPTs provide a good tool to investigate early stages of pancreatic carcinogenesis. Thus, to clarify genetic alterations in the early stage of pancreatic carcinogenesis, we analyzed K-ras gene mutations and loss of heterozygosity (LOH) at the p53 gene locus using 37 cases of MPTs harboring dysplastic epithelium. Further, we conducted an extended, multifocal microdissection analysis focusing on the histological features of ductal epithelium and the distribution of genetic alterations for 3 cases of MPT positive for LOH of the p53 gene to determine the relation to tumor progression. K-ras gene mutations were detected with high frequency in 50% or more cases of the adenomas (14 of 19), borderline tumors (4 of 7), and carcinomas (8 of 11), whereas LOH of the p53 gene was limited to carcinomas (3 of 5 informative cases, 60%) and always accompanied by K-ras gene mutation. Investigation of a total of 126 microdissection sites from 3 cases showed the presence of K-ras gene mutations in mild dysplasia and all (100%) regions of moderate or more marked dysplasia, whereas LOH of the p53 gene showed more gradual tendency to increase with grade from moderate dysplasia. In addition, the multifocal genetic analysis showed K-ras gene mutations to be widely distributed throughout tumors, whereas LOH of the p53 gene was localized to 1 or a few areas. Further, topographically delimited areas with the same histology in the same tumor did not always show the same genetic alteration. In conclusion, we could confirm that both the K-ras and p53 gene alterations occur in the intraductal stage of MPT, and the latter is superimposed on the former during the course of tumor progression. However, the pattern of association of histological features with genetic alteration differs from tumor to tumor.


Assuntos
Genes p53 , Genes ras , Perda de Heterozigosidade , Mucinas/biossíntese , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Epitélio/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo
14.
J Cancer Res Clin Oncol ; 125(8-9): 439-43, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10480335

RESUMO

PURPOSE: This present study aimed to investigate the genetic changes in gallbladder carcinogenesis. METHODS: Eleven intramucosal gallbladder carcinomas were compared with 31 invasive lesions for loss of heterozygosity (LOH) on chromosomes 5q, 9p, 17p and 18q, frame-shift mutations in a ten-adenine repeat site within the gene encoding the transforming growth factor beta type II receptor (TGFbetaRII) and an eight-guanine repeat site within BAX, and point mutations in codon 12 of Ki-ras. RESULTS: The incidences of LOH in intramucosal and invasive carcinomas were 14% and 17% on 5q, 9% and 52% on 9p, 64% and 65% on 17p, and 13% and 32% on 18q. No frame-shift mutations were found at TGFbetaRII or BAX, and point mutations in codon 12 of Ki-ras were present in only 8% of the samples. Thus, LOH on 17p was by far the most frequent lesion with similar results in both intramucosal and invasive carcinomas. In contrast, the frequency of LOH on 9p and 18q was distinctly higher in invasive lesions. CONCLUSION: The present data suggest that LOH on 17p may play an important role in the evolution of gallbladder carcinoma from a relatively early phase, while LOH on 9p and 18q may play roles in progression.


Assuntos
Carcinoma/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 5/genética , Cromossomos Humanos Par 9/genética , Mutação da Fase de Leitura , Neoplasias da Vesícula Biliar/genética , Genes ras/genética , Perda de Heterozigosidade , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Proteínas ras/genética , Adenina/metabolismo , Adenocarcinoma/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Carcinoma de Células Pequenas/genética , Carcinoma de Células Escamosas/genética , Feminino , Neoplasias da Vesícula Biliar/patologia , Guanina/metabolismo , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Invasividade Neoplásica , Reação em Cadeia da Polimerase/métodos , Proteínas Serina-Treonina Quinases , Receptor do Fator de Crescimento Transformador beta Tipo II , Proteína X Associada a bcl-2
15.
Am J Clin Pathol ; 110(3): 368-73, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9728612

RESUMO

To establish an effective and reliable system for the detection of p53 mutations, we evaluated the detection efficiencies of nonisotopic polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP), fluorescence in situ hybridization (FISH), and immunohistochemistry. Ten cell lines (AsPc1, BxPc3, Miapaca2, Panc1, Colo320-011, Lovo, MCF7, LNCaP, HL-60, and Daudi), a peripheral blood sample from a patient with a p53 germline mutation (p53GML), and a normal peripheral blood sample were used for examination. Direct nucleotide sequencing identified p53 mutations in 7 of 12 samples (AsPc1, BxPc3, Miapaca2, Panc1, Colo320-011, HL-60, and p53GML). The nonisotopic PCR-SSCP detected anomalies of the PCR fragments in 5 cell lines. In the FISH analysis, 2 cell lines exhibited loss of heterozygosity of the p53 locus. Immunohistochemistry detected an accumulation of the abnormal p53 in 4 cell lines. The combination of these 3 methods produced no false-negative or false-positive results. This combination may be an excellent and beneficial system for the clinical diagnosis of the various human cancers.


Assuntos
DNA de Neoplasias/análise , Genes p53/genética , Mutação , Proteína Supressora de Tumor p53/genética , Linhagem Celular , Análise Mutacional de DNA , Estudos de Avaliação como Assunto , Reações Falso-Positivas , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Perda de Heterozigosidade , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Análise de Sequência de DNA , Proteína Supressora de Tumor p53/metabolismo
16.
Virchows Arch ; 432(4): 315-22, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9565340

RESUMO

Adenoma malignum of the uterine cervix (mucinous type of minimal deviation adenocarcinoma, mucinous MDA), is a unique neoplasm that is difficult to diagnose owing to the deceptively benign appearance of the tumour cells. The present study was undertaken to explore the phenotypic expression of this tumour compared with those of non-neoplastic cervical tissues and of cervical carcinomas of various types. Ten cases of mucinous MDA, 50 cases with non-neoplastic cervical tissues, 13 of cervical adenocarcinoma including the mucinous (endocervical or intestinal type) and endometrioid types, and 2 of mucoepidermoid carcinoma were examined by various histochemical staining methods, including those for gastric mucins, pepsinogen, lysozyme, chromogranin A and carcinoembryonic antigen. The results revealed that mucinous MDA characteristically exhibited gastric phenotypes. The presence of gastric metaplasia was also demonstrated in 9 cases of mucinous MDA and in 5 of the other cases examined. The 7 endocervical-type adenocarcinomas also included 4 that expressed gastric phenotypes, and 2 of the 3 intestinal-type adenocarcinomas showed the same properties focally. These results indicate the presence of a group of lesions expressing gastric phenotypes in the uterine cervix and suggest a close relationship between these lesions. Cervical adenocarcinomas expressing gastric phenotypes are probably derived from MDA.


Assuntos
Adenocarcinoma Mucinoso/química , Mucinas/análise , Neoplasias do Colo do Útero/química , Adolescente , Adulto , Cromogranina A , Cromograninas/análise , Feminino , Histocitoquímica , Humanos , Metaplasia , Pessoa de Meia-Idade , Muramidase/análise , Ácidos Neuramínicos/análise , Pepsinogênios/análise , Estômago/química , Estômago/patologia
17.
Ann Clin Lab Sci ; 31(2): 163-70, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11337906

RESUMO

In a proband (21-yr-old female), we previously identified an apolipoprotein (apo) E variant, apoE3 (Arg 145-->His), with an isoelectric point midway between apoE3 and apoE2. ApoE gene analysis of 4 of the proband's kin indicated that 3 possess the same variant. All 4 had a high concentration of apoE in plasma, while 3 of 4 had hypertriglyceridemia. In the proband (who had no hypertriglyceridemia), most apoE was distributed in slow-alpha lipoproteins (predominantly in the form of apoE-AII heterodimer) and in larger molecules with apparent molecular weights of 80 and 100 kDa. In the proband's brother (with hypertriglyceridemia), however, most apoE was distributed in slow pre-beta lipoproteins, predominantly in the form of monomeric apoE. In each subject, the concentration of apoE3 variant was significantly higher than that of normal apoE3 in the predominant apoE-rich lipoprotein. The apoE3 variant, which displayed a slightly reduced binding ability to LDL-receptor and heparin, may induce an accumulation of apoE-rich lipoproteins. These observations suggest that the difference in distribution of apoE3 variant in plasma lipoproteins between the proband and her brother (combined with its reduced affinity for the LDL receptor) may provide key insights into the pathogenesis of hypertriglyceridemia.


Assuntos
Apolipoproteínas E/genética , Variação Genética , Hipertrigliceridemia/genética , Adulto , Apolipoproteínas E/sangue , Apolipoproteínas E/química , Cromatografia de Afinidade , Eletroforese em Gel de Ágar , Eletroforese em Gel Bidimensional , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Focalização Isoelétrica , Ponto Isoelétrico , Masculino , Fenótipo , Receptores de LDL/metabolismo
18.
Rinsho Byori ; 48(1): 31-7, 2000 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-10756672

RESUMO

Molecular diagnostic tests and chromosomal analyses are often used to diagnose infectious, neoplastic and genetic diseases. However, there are only a few genetic laboratories in university hospitals in Japan because of the high cost and additional staff required for their management. In 1992, we started a genetic laboratory with one technologist in Shinshu University Hospital, and mainly performed polymerase chain reactions(PCR) for the diagnosis of several mycobacterial species, Hepatitis C virus and cytomegalovirus. Infectious diseases diagnosed by PCR have gradually increased over recent years. Chromosome analyses were available in 1996 and spectral karyotyping started from April 1999. Our genetic laboratory was staffed by 4 technologists and 3 faculty members in 1999, and they can provide informative tests with high quality. Molecular diagnostic tests were performed for 855 infectious diseases, 25 hematopoietic tumors and 8 solid tumors, while chromosome analyses were performed for 51 hereditary diseases and 29 hematopoietic tumors in 1998. Establishment of a genetic laboratory in a university hospital may not result in cost savings, but it produces a favorable influence on other laboratories. All staff can use molecular biology techniques to clarify limitations of routine tests and research.


Assuntos
Doenças Genéticas Inatas/genética , Infecções/genética , Neoplasias/genética , Cromossomos , Humanos , Mycobacterium/genética , Reação em Cadeia da Polimerase , Tuberculose/microbiologia , Viroses/virologia
19.
Rinsho Byori ; 48(10): 955-9, 2000 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-11215110

RESUMO

FISH analysis using X alpha satellite probe was performed to the nuclei of lymphocytes obtained from fourteen women with having a history of habitual abortion for unknown causes(WHA) and from 65 normal control women(NW), in order to determine whether low frequency X monosomy mosaicism is one of the factors of habitual abortion. In parallel, the nuclei of buccal mucosa from 8 of WHA and 65 NW were also examined. Five hundreds of the interphase nuclei in each sample were observed. As results, the frequency of X monosomy in NW found in the lymphocytes or buccal mucosa was ranged from 0-3.2%(mean 1.59%, SD 0.69%) or from 0-3.2%(mean 1.24%, SD 0.85%), respectively. However, the occurrence of X monosomy in WHA was significantly higher compared with that of NW; i.e., 0.8-5.8%(mean 3.21%, SD 1.67) for lymphocytes, and 1.8-7.4%(mean 4.45%, SD 1.73%) for buccal mucosa. These results allowed us to define the reference intervals to discriminate WHA from NW were less than 2.97% or 2.94% for lymphocytes or buccal mucosa, respectively. Based on the reference intervals defined above, the high frequency of X monosomy mosaicism was actually found in 9 of 14 WHA. These results altogether strongly suggested that the low frequency X monosomy mosaicism was one of the factors of habitual abortion.


Assuntos
Aborto Habitual/genética , Hibridização in Situ Fluorescente , Linfócitos , Monossomia , Mosaicismo , Mucosa Bucal/citologia , Cromossomo X/genética , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez
20.
Rinsho Byori ; 46(2): 151-7, 1998 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-9528339

RESUMO

The COBAS Amplicor system is an automated diagnostic PCR system which contains a PCR internal control (P. I. C.) template to monitor the amplification. The applicability of COBAS Amplicor HCV was examined using sera of patients with hepatitis. Furthermore, the effects of possible interfering substance (total protein, triglyceride, hemoglobin, glucose, total bilirubin, heparin, lysis reagent including guanidium) on HCV-RNA detection were investigated. The sensitivity of COBAS Amplicor HCV was equivalent to the manual method of Amplicor HCV, moreover all of the results in 54 clinical samples analyzed on both COBAS Amplicor HCV and Amplicor HCV were in agreement. Detection sensitivity of HCV-RNA decreased in the presence of total bilirubin and heparin. Ten and 25mg/dl of total bilirubin affected HCV-RNA detection but did not affect P. I. C. This result suggested that total bilirubin interfered with the protein denature caused by the lysis reagent. Fifteen U/ml of heparin in the sample completely inhibited amplification both of the HCV-RNA and P. I. C. One U/ml of heparin did not affect amplification, but heparinized blood samples should not be used for the detection of HCV-RNA. To examine the effect of possible carry over contamination on the lysis reagent which contains guanidium, various concentrations of lysis reagent in P. I. C. were tested. RT-PCR was inhibited by 1/500 volume contamination of lysis reagent in specimen diluent. Other substances did not affect the sensitivity. Our results indicate that the carryover contamination of lysis reagent cause more "false negative" results than interfering substances in sera. In conclusion, HCV-RNA detection system containing P. I. C., such as COBAS Amplicor HCV, will become a very useful to differentiate "false negative" and "true negative" result.


Assuntos
Hepacivirus/genética , Reação em Cadeia da Polimerase/instrumentação , RNA Viral/análise , Bilirrubina , Heparina , Humanos , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Sensibilidade e Especificidade
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