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1.
Virus Res ; 347: 199418, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38880337

RESUMEN

Although it is generally believed that large DNA viruses capture genes by horizontal gene transfer (HGT), the detailed manner of such transfer has not been fully elucidated. Here, we searched for genes in the coleopteran entomopoxvirus (EV) Anomala cuprea entomopoxvirus (ACEV) that might have been gained by ACEV by HGT. We classified the potential source organisms for HGT into three categories: the host A. cuprea; other organisms, including viruses unrelated to EVs; and organisms with uncertain host attribution. Of the open reading frames (ORFs) of the ACEV genome, 2.1 % were suggested to have been gained from the host by ACEV or its recent ancestor via HGT; 8.7 % were possibly from organisms other than the host, and 3.7 % were possibly from the third category of organisms via HGT. The analysis showed that ACEV contains some interesting ORFs obtained by HGT, including a large ATP-binding cassette protein (ABC transporter) ORF and a tenascin ORF (IDs ACV025 and ACV123, respectively). We then performed a detailed analysis of the HGT of the ACEV large ABC transporter ORF-the largest of the ACEV ORFs. mRNA sequences obtained by RNA-seq from fat bodies-sites of ACEV replication-and midgut tissues-sites of initial infection-of the virus's host A. cuprea larvae were subjected to BLAST analysis. One type of ABC transporter ORF from the fat bodies and two types from the midgut tissues, one of which was identical to that in the fat bodies, had the greatest identity to the ABC transporter ORF of ACEV. The two types from the host had high levels of identity to each other (approximately 95 % nucleotide sequence identity), strongly suggesting that the host ABC transporter group consisting of the two types was the origin of ACV025. We then determined the sequence (12,381 bp) containing a full-length gene of the A. cuprea ABC transporter. It turned out to be a transcription template for the abovementioned mRNA found in both tissues. In addition, we determined a large part (ca. 6.9 kb) of the template sequence for the mRNA found only in the midgut tissues. The results showed that the ACEV ABC transporter ORF is missing parts corresponding to introns of the host ABC transporter genes, indicating that the ORF was likely acquired by HGT in the form of mRNA. The presence of definite duplicated sequences adjacent to the ACEV ABC transporter genes-a sign of LINE-1 retrotransposon-mediated HGT-was not observed. An approximately 2-month ACV025 transcription experiment suggested that the transporter sequence is presumed to be continuously functional. The amino acid sequence of ACV025 suggests that its product might function in the regulation of phosphatide in the host-cell membranes.

2.
Nat Commun ; 14(1): 1357, 2023 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-36914655

RESUMEN

In most eukaryotes, biparentally inherited nuclear genomes and maternally inherited cytoplasmic genomes have different evolutionary interests. Strongly female-biased sex ratios that are repeatedly observed in various arthropods often result from the male-specific lethality (male-killing) induced by maternally inherited symbiotic bacteria such as Spiroplasma and Wolbachia. However, despite some plausible case reports wherein viruses are raised as male-killers, it is not well understood how viruses, having much smaller genomes than bacteria, are capable of inducing male-killing. Here we show that a maternally inherited double-stranded RNA (dsRNA) virus belonging to the family Partitiviridae (designated DbMKPV1) induces male-killing in Drosophila. DbMKPV1 localizes in the cytoplasm and possesses only four genes, i.e., one gene in each of the four genomic segments (dsRNA1-dsRNA4), in contrast to ca. 1000 or more genes possessed by Spiroplasma or Wolbachia. We also show that a protein (designated PVMKp1; 330 amino acids in size), encoded by a gene on the dsRNA4 segment, is necessary and sufficient for inducing male-killing. Our results imply that male-killing genes can be easily acquired by symbiotic viruses through reassortment and that symbiotic viruses are hidden players in arthropod evolution. We anticipate that host-manipulating genes possessed by symbiotic viruses can be utilized for controlling arthropods.


Asunto(s)
Drosophila melanogaster , Genes Virales , Virus de Insectos , Razón de Masculinidad , Simbiosis , Drosophila melanogaster/embriología , Drosophila melanogaster/virología , Virus de Insectos/genética , Genes Virales/fisiología , Masculino , Animales , Desarrollo Embrionario , ARN Viral/fisiología , ARN Bicatenario/fisiología , Evolución Molecular , Sistemas de Lectura Abierta/genética , Caracteres Sexuales , Femenino
3.
PNAS Nexus ; 2(1): pgac293, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36712932

RESUMEN

Wolbachia, a maternally transmitted bacterium, shows male-killing, an adaptive phenotype for cytoplasmic elements, in various arthropod species during the early developmental stages. In lepidopteran insects, lethality of males is accounted for by improper dosage compensation in sex-linked genes owing to Wolbachia-induced feminization. Herein, we established Ostrinia scapulalis cell lines that retained sex specificity per the splicing pattern of the sex-determining gene doublesex (Osdsx). We found that Wolbachia transinfection in male cell lines enhanced the female-specific splice variant of Osdsx (OsdsxF ) while suppressing the male-specific variant (OsdsxM ), indicating that Wolbachia affects sex-determining gene signals even in vitro. Comparative transcriptome analysis isolated only two genes that behave differently upon Wolbachia infection. The two genes were respectively homologous to Masculinizer (BmMasc) and zinc finger-2 (Bmznf-2), male-specifically expressed sex-determining genes of the silkworm Bombyx mori that encode CCCH-type zinc finger motif proteins. By using cultured cells and organismal samples, OsMasc and Osznf-2 were found to be sex-determining genes of O. scapulalis that are subjected to sex-specific alternative splicing depending upon the chromosomal sex, developmental stage, and infection status. Overall, our findings expound the cellular autonomy in insect sex determination and the mechanism through which sex is manipulated by intracellular selfish microbes.

4.
Front Microbiol ; 13: 1031535, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36425043

RESUMEN

The poultry red mite Dermanyssus gallinae poses a significant threat to the health of hens and poultry production. A comprehensive understanding of D. gallinae is necessary to develop sustainable and efficacious control methods. Here we examined 144 D. gallinae collected from 18 poultry farms throughout the Japanese Archipelago for their genetic variations based on mitochondrial cytochrome c oxidase subunit I (COI) sequences, and microbiome variations based on amplicon sequencing of the 16S ribosomal RNA gene. According to COI sequencing, the Japanese samples were categorized into three haplogroups, which did not reflect the geographical distribution. Microbiome analyses found that the major bacteria associated with D. gallinae were Bartonella, Cardinium, Wolbachia, and Tsukamurella, with Bartonella being most predominant. Among 144 individual mites, all possessed one of the two major types of Bartonella (Bartonella sp. A), while 140 mites possessed the other type (Bartonella sp. B). The presence of the two strains of Bartonella was also confirmed by a single copy gene, rpoB. The presence of Bartonella in laid eggs suggested transovarial vertical transmission. Given that obligate blood-feeding arthropods generally require a supply of B vitamins from symbiotic bacteria, Bartonella may play an important role in mite survival. Rickettsiella, a major symbiont in European D. gallinae populations, and suggested to be an important symbiont by genomic data, was rarely found in Japanese populations. Cardinium detected from D. gallinae fell into a major clade found widely in arthropods, whereas Wolbachia detected in Japanese D. gallinae appear to be a new lineage, located at the base of Wolbachia phylogeny. Of the mitochondrial phylogeny, infection patterns of Cardinium and Wolbachia were strongly correlated, possibly suggesting one or both of the symbionts induce reproductive manipulations and increase spread in the host populations.

5.
In Vitro Cell Dev Biol Anim ; 58(7): 610-618, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35867318

RESUMEN

Insect contractile cells frequently appear at an early phase of cell culture, but in most cases, they disappear before a continuous cell line is established, so the cell line ceases to contract. Continuous contractile insect cell lines are currently available from only one species each of Hymenoptera and Diptera. Here, we obtained a new cell line that contracted long after being established as a continuous cell line. The cell line contracted for a short period at an early phase of insect cell culture before a continuous cell line was established, but then did not contract again for several years. After this cell line entered the continuous growth phase, it produced spontaneously contractile tissues for about 4 mo but stopped contracting again. This is the first instance of a cell line that contracted after its establishment as a non-contractile continuous cell line. It is unclear whether the contractile cells survive or die after contraction ceases at an early phase of cell culture, and our results indicate that potential contractile cells survive for years after they stop to contract. The cells of this line sometimes produced complex contractile structures, such as sheet-like tissues. Only a few continuous cell lines have been derived from scarabaeid beetles. The new continuous cell line was derived from the culture of the fat bodies of the scarab beetle Anomala cuprea, which is a pest in the agriculture and forestry of Japan. The population doubling time of the new cell line was 2.5 d and thus it grows very rapidly among coleopteran continuous cell lines. Our new cell line will facilitate research on the physiology and pathology of Coleoptera, including scarab beetles, and may also contribute to research on invertebrate muscles.


Asunto(s)
Escarabajos , Animales , Técnicas de Cultivo de Célula , Línea Celular
6.
Arch Virol ; 164(1): 17-25, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30225520

RESUMEN

Oral inoculation of entomopoxvirus spindles, microstructures composed of fusolin protein, causes disruption of the peritrophic matrix (PM), a physical barrier against microbe infection, in the insect midgut. Although the atomic structure of fusolin has been determined, little has been directly elucidated of the mechanism of disruption of the PM. In the present study, we first performed an immunohistochemical examination to determine whether fusolin acts on the PM directly or indirectly in the midgut of Bombyx mori larvae that were inoculated with spindles of Anomala cuprea entomopoxvirus. This revealed that the PM, rather than the midgut cells, was the attachment site for fusolin. Fusolin broadly attached to the PM from the anterior to the posterior region, both to its ectoperitrophic and endoperitrophic surfaces and within the PM. These results likely explain why the whole of the PM is rapidly disintegrated. Second, we administered protease inhibitors mixed with spindles and observed decreased midgut protease activity and reduced disruption of the PM. This suggests that midgut protease(s) is also positively involved in PM disruption. Based on the present results, we propose an overall mechanism for the disruption of the PM by administration of fusolin.


Asunto(s)
Bombyx/efectos de los fármacos , Tracto Gastrointestinal/efectos de los fármacos , Péptido Hidrolasas/metabolismo , Proteínas Virales/farmacología , Administración Oral , Animales , Insecticidas/farmacología , Larva/efectos de los fármacos
7.
Biol Lett ; 13(10)2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29021316

RESUMEN

A maternally inherited, all-female trait is widely found among arthropods, which is caused by bacterial endosymbionts such as Wolbachia, Rickettsia, Spiroplasma and Cardinium We discovered a single female of Drosophila biauraria, collected from Tomakomai, Hokkaido, Japan, that produced all-female offspring. This all-female trait was maternally inherited in the iso-female line (SP12F) by backcrossing with males of a normal line (SP11-20) with a 1 : 1 sex ratio derived from the same population. The all-female trait was not affected by tetracycline treatment performed for two consecutive generations. However, the microinjection of filter-sterilized homogenate of SP12F females into SP11-20 females established all-female matrilines. Our data suggest the role of transmissible agents, most likely viruses, but not bacteria or protists, as the possible cause of the all-female phenotype, which is likely to be achieved by killing of male embryos because egg hatch rates of SP12F were nearly half those of SP11-20. This is the first report in Diptera to demonstrate a maternally inherited virus-like element as the cause of the male-killing phenotype in D. biauraria.


Asunto(s)
Drosophila/fisiología , Animales , Antibacterianos/farmacología , Femenino , Japón , Masculino , Herencia Materna , Fenotipo , Reacción en Cadena de la Polimerasa , Razón de Masculinidad , Simbiosis , Tetraciclina/farmacología
8.
J Dig Dis ; 17(10): 670-675, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27534444

RESUMEN

OBJECTIVE: Vonoprazan is a potassium-competitive acid blocker, a new type of acid-suppressing drug, and has recently become available for peptic ulcers, gastroesophageal reflux disease, and Helicobacter pylori (H. pylori) eradication. Its efficacy for H. pylori eradication has been reported. However, the evidence for its efficacy and feasibility remains limited. We aimed to compare the feasibility, effectiveness and safety of vonoprazan-based triple therapy with conventional proton pump inhibitor (PPI)-based triple therapy in multicenter clinical practice. METHODS: We performed a multicenter retrospective study on patients receiving first-line H. pylori eradication therapy between March 2013 and November 2015 with either vonoprazan-based triple therapy or conventional PPI-based triple therapy. RESULTS: A total of 2715 patients aged 63.0 ± 12.1 years (1412 [52.0%] males) were analyzed. Eradication rates were 87.2% (368/422) for vonoprazan-based therapy and 72.4% (1661/2293) for conventional PPI-based therapy (P < 0.01). Among the former group, there were 10 cases of diarrhea, six of nausea/vomiting, and five of rash, but the rates of these adverse events were similar to those in the conventional PPI group. CONCLUSION: Vonoprazan-based triple therapy is feasible, and has a higher rate for H. pylori eradication than conventional PPI as a first-line regimen.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Inhibidores de la Bomba de Protones/uso terapéutico , Pirroles/uso terapéutico , Sulfonamidas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amoxicilina/uso terapéutico , Antiulcerosos/uso terapéutico , Claritromicina/uso terapéutico , Quimioterapia Combinada , Estudios de Factibilidad , Femenino , Infecciones por Helicobacter/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/efectos adversos , Pirroles/efectos adversos , Estudios Retrospectivos , Sulfonamidas/efectos adversos , Resultado del Tratamiento , Adulto Joven
9.
World J Surg Oncol ; 14: 52, 2016 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-26911980

RESUMEN

BACKGROUND: The outcomes of treatment of ruptured varices in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) are unclear. We therefore evaluated the long- (rebleeding and death) and short-term (immediate death within 24 h of variceal bleeding diagnosis) outcomes of patients with PVTT who underwent emergency variceal band ligation. METHODS: Data on 62 patients with PVTT and endoscopically proven esophageal or gastric variceal bleeding from 2007 to 2012 were studied. In most cases, the varices were treated using endoscopic variceal band ligation (EVL). We assessed the patients' rebleeding-free and overall survival using the Kaplan-Meier method, and a Cox proportional hazard model was used to analyze effect of independent factors on rebleeding-free and overall survival times. RESULTS: Most patients had decompensated cirrhosis and were classified as Child-Pugh class B (56%) or C (36%). A total of 35 patients (56%) had PVTT in the main portal trunk. Among all patients, 58 (94%) and 4 (6%) had esophageal and gastric variceal bleeding, respectively. Bleeding was managed using EVL in all, but one patient (98%) who was treated with a Sengstaken-Blakemore tube. A total of 24 patients (39.3%) experienced rebleeding, and these patients had a median overall survival time of 36 days. A PVTT in the main portal trunk was predictive of rebleeding (hazard ratio 3.706, p = .0223), and α-fetoprotein-L3 levels <37.4% (hazard ratio 0.464, p = 0.015) and Child-Pugh class A/B (hazard ratio 0.398, p = 0.007) were associated with overall survival. We observed 95 bleeding events in 62 patients. EVL achieved hemostasis in 92 of the 95 bleeding events, whereas seven immediate deaths occurred due to variceal bleeding (7/92, 7.6%). All three bleeding events treated with modalities other than EVL resulted in immediate deaths. CONCLUSIONS: EVL is a safe and effective treatment of variceal ruptures in patients with HCC and PVTT. After successful hemostasis, alleviation of the underlying liver function impairment and tumor control are equally important for a good prognosis.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hemorragia/complicaciones , Neoplasias Hepáticas/cirugía , Vena Porta/cirugía , Cirugía Asistida por Computador/métodos , Várices/cirugía , Trombosis de la Vena/cirugía , Adulto , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Endoscopía/métodos , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Vena Porta/patología , Pronóstico , Estudios Retrospectivos , Várices/etiología , Várices/patología , Trombosis de la Vena/complicaciones , Trombosis de la Vena/patología
10.
Insect Biochem Mol Biol ; 66: 72-6, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26453817

RESUMEN

Endosymbiotic bacteria of the genus Wolbachia often manipulate the reproductive system of their hosts to propagate themselves in host populations. Ostrinia scapulalis moths infected with Wolbachia (wSca) produce female-only progeny (sex chromosomes: ZW), whereas females cured of the infection by antibiotic treatment produce male-only progeny (ZZ). The occurrence of female- and male-only progeny has been attributed to the specific death of the opposite sex during embryonic and larval development. In this bidirectional sex-specific lethality, embryos destined to die express a phenotypic sex opposite to their genotypic sex. On the basis of these findings, we suggested that wSca carries a genetic factor that feminizes the male host, the W chromosome of the host has lost its feminizing function, and discordance between the genotypic and phenotypic sexes underlies this sex-specific death. In the present study, we examined whether the failure of dosage compensation was responsible for this sex-specific mortality. Quantitative PCRs showed that Z-linked gene expression levels in embryos destined to die were not properly dosage compensated; they were approximately two-fold higher in the male progeny of wSca-infected females and approximately two-fold lower in the female progeny of infected-and-cured females. These results support our hypothesis that misdirection of dosage compensation underlies the sex-specific death.


Asunto(s)
Compensación de Dosificación (Genética) , Mariposas Nocturnas/genética , Mariposas Nocturnas/microbiología , Wolbachia/fisiología , Animales , Muerte , Femenino , Genotipo , Larva/genética , Larva/crecimiento & desarrollo , Larva/microbiología , Masculino , Mariposas Nocturnas/crecimiento & desarrollo , Cromosomas Sexuales , Diferenciación Sexual , Razón de Masculinidad , Tetraciclina/farmacología
11.
J Dig Dis ; 16(11): 649-55, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26356801

RESUMEN

OBJECTIVE: Patients who take drugs regularly are increasing, not least due to metabolic and orthopedic diseases. In the present study we aimed to investigate the association between the use of drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin, and colorectal polyps diagnosed based on colonoscopic findings. METHODS: In total, 1318 consecutive patients who underwent total colonoscopy for the first time were cross-sectionally analyzed. Personal data including comorbidities and all medications were obtained by a questionnaire. Their blood pressure, body weight and waist circumference were measured just before the colonoscopic examination. RESULTS: Colorectal polyps were found in 577 (43.8%) patients, with a prevalence of 57.6% (296/514) in patients receiving antihypertensive treatment and 35.0% (281/804) in patients not undergoing such treatment. A multivariate analysis showed that age, waist circumference, alcohol consumption, smoking and the use of antihypertensive drugs were independent risk factors for colorectal polyps. In a secondary multivariate analysis incorporating the parameters of measured blood pressure and medication status, the number of antihypertensive drugs was strongly associated with the risk of colorectal polyps, whereas blood pressure showed no significant association. CONCLUSIONS: The use of antihypertensive drug may be a risk factor for colorectal polyps. Furthermore, this risk increases with the intensive use of antihypertensive drugs.


Asunto(s)
Antihipertensivos/efectos adversos , Neoplasias Colorrectales/inducido químicamente , Pólipos Intestinales/inducido químicamente , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Presión Sanguínea/fisiología , Pólipos del Colon/inducido químicamente , Pólipos del Colon/fisiopatología , Colonoscopía , Neoplasias Colorrectales/fisiopatología , Estudios Transversales , Femenino , Humanos , Pólipos Intestinales/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo
12.
J Insect Physiol ; 81: 48-51, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26142572

RESUMEN

Maternally inherited endosymbiotic bacteria of the genus Wolbachia cause various reproductive alterations in their hosts. Wolbachia induces male-specific death during embryonic and larval stages in the moth Ostrinia scapulalis. To investigate how the density of Wolbachia affects their performance in the host, we attempted to reduce its density using a short, high-temperature treatment of the host at the larval stage. Individuals cured of infection as well as sexual mosaics, which harbor Wolbachia, were obtained by this method in the next generation. The sex of uninfected offspring was exclusively male, similar to that of the offspring of larvae treated with antibiotics. A strong correlation was found between Wolbachia density in female moths and the sex ratio of their progeny. These results suggest that a short, high-temperature treatment at the larval stage reduced the density of Wolbachia in the adult stage, and, hence, inhibited interference with the host's development in the next generation. Since the direct effects of the heat treatment on Wolbachia were transient, this method may be useful for specifying the critical time for interference by Wolbachia in host development.


Asunto(s)
Mariposas Nocturnas/microbiología , Wolbachia/fisiología , Animales , Antibacterianos/farmacología , Femenino , Interacciones Huésped-Patógeno , Calor , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Larva/microbiología , Masculino , Mosaicismo , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/crecimiento & desarrollo , Razón de Masculinidad , Tetraciclina/farmacología
13.
Can J Gastroenterol Hepatol ; 29(6): 321-5, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26069891

RESUMEN

BACKGROUND: Endoscopic submucosal dissection (ESD) of early gastric cancer is a minimally invasive procedure. However, the risk for metachronous cancers after successful cancer treatment remains high and the risk factors for metachronous cancers have not been elucidated. OBJECTIVE: To evaluate the risk factors for metachronous gastric cancers after ESD with a long-term follow-up. METHODS: A total of 155 consecutive patients (119 men, 36 women, mean age 68.9 years) were treated with ESD between September 2000 and September 2009. Biopsy specimens were obtained from the greater curvature of the antrum and middle corpus to evaluate gastric mucosal status, including Helicobacter pylori, intestinal metaplasia (IM) and neutrophil infiltration (NI) before ESD. Follow-up endoscopy after ESD was scheduled at two and six months, one year and annually thereafter. H pylori eradication was recommended when possible. RESULTS: The median follow-up period was 4.2 years. Metachronous gastric cancers were found in 23 of 155 patients (3.5% per year). No local recurrences were observed. The cumulative incidence of metachronous gastric cancer was significantly high in IM and NI in the corpus (P=0.0093 and P=0.0025, respectively [log-rank test]). The ORs for IM and NI in the corpus were 2.65 and 3.06, respectively, according to the Cox proportional hazards model (P=0.024 and P=0.0091, respectively). CONCLUSIONS: The presence of IM and NI in the corpus was closely related to the development of metachronous gastric cancer after ESD.


Asunto(s)
Disección/efectos adversos , Intestinos/patología , Neoplasias Primarias Secundarias/epidemiología , Infiltración Neutrófila , Neoplasias Gástricas/inmunología , Anciano , Anciano de 80 o más Años , Disección/métodos , Femenino , Estudios de Seguimiento , Mucosa Gástrica/cirugía , Gastroscopía , Helicobacter pylori , Humanos , Masculino , Metaplasia , Persona de Mediana Edad , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía
14.
Hepatol Int ; 9(1): 142-8, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25788388

RESUMEN

PURPOSE: The prognosis in advanced biliary carcinoma has remained poor. The purpose of this study was to investigate the efficacy of intraarterial 5-fluorouracil and interferon therapy against unresectable biliary carcinoma. METHODS: Patients with unresectable biliary carcinoma with performance status 0 or 1 were enrolled between January 2002 and September 2012. They received pegylated interferon-α 2a and intraarterial 5-FU every 4 weeks. The therapy was either terminated at the end of the first cycle for the patients with progressive disease or continued for at least three cycles. Patients' characteristics (physical, laboratory and radiographic) at the time of starting intraarterial 5-FU therapy were investigated. The relationship between the patients' characteristics and outcome, i.e., survival time and radiographic therapeutic evaluation of patients, was statistically analyzed. RESULTS: Tumor sites were the intrahepatic bile ducts in 23 patients and gallbladder in 2 patients. Previous treatment had been administered in ten patients. The overall response rate was 24% (6 partial responses in 25 patients). Stable disease was observed in 13 patients. The median overall survival was 358 days. Among the six partial responses, three patients received surgery, and one patient received radiofrequency ablation because clinical downstaging was obtained. The treatment was well tolerated. The survival analyses revealed that two factors (serum albumin ≥ 3.5 and hypovascular tumor) were significantly associated with overall survival. CONCLUSIONS: Combination therapy with 5-FU and interferon-α was safe and may improve the prognosis of advanced biliary carcinomas.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Conductos Biliares Intrahepáticos , Colangiocarcinoma/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de los Conductos Biliares/irrigación sanguínea , Colangiocarcinoma/irrigación sanguínea , Femenino , Fluorouracilo/administración & dosificación , Neoplasias de la Vesícula Biliar/irrigación sanguínea , Humanos , Infusiones Intraarteriales , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Albúmina Sérica/análisis , Tasa de Supervivencia , Resultado del Tratamiento
15.
Clin J Gastroenterol ; 7(6): 481-3, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25491906

RESUMEN

Restorative proctocolectomy has become the most common surgical option for familial adenomatous polyposis patients, based on the premise that the technique yields good functional results and reduces colorectal cancer risk. However, several adenomas may develop in the pouch mucosa in later years, and even cancer (at the anastomosis or in the pouch mucosa) has been reported. Endoscopic submucosal dissection (ESD) would then be indicated, even if severe fibrosis extended into the submucosal layer. Endoscopic resection of an ileal tumor from the thin wall of the ileum carries a high-risk of perforation. Our present case demonstrates the successful use of ESD to treat an ileal neoplasm, a technically difficult lesion with a high-risk of complications.


Asunto(s)
Adenoma/cirugía , Poliposis Adenomatosa del Colon/cirugía , Reservorios Cólicos/efectos adversos , Disección/métodos , Endoscopía Gastrointestinal/métodos , Neoplasias del Íleon/cirugía , Proctocolectomía Restauradora/efectos adversos , Adenoma/etiología , Adenoma/patología , Poliposis Adenomatosa del Colon/complicaciones , Adulto , Canal Anal/cirugía , Anastomosis Quirúrgica/efectos adversos , Humanos , Neoplasias del Íleon/etiología , Neoplasias del Íleon/patología , Íleon/cirugía , Mucosa Intestinal/cirugía , Masculino , Factores de Tiempo
16.
J Dig Dis ; 13(7): 374-80, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22713087

RESUMEN

OBJECTIVE: The study was aimed to assess the efficacy of sodium phosphate (NaP) tablets and polyethylene glycol (PEG) on colon cleansing. METHODS: A prospective, randomized trial was conducted at the Graduate School of Medicine, University of Tokyo. Participants who were scheduled for colonoscopy were included and randomized into either the NaP or PEG group. An interim analysis was programmed into the study design when approximately 50% of the enrolments were completed. The primary outcome was the detection rate of polyps with a diameter ≤5 mm. RESULTS: A total of 92 patients were included in the analysis, of whom 44 were in the NaP group and 48 in the PEG group. The quality of colonic preparation was similar in both groups. The NaP group showed a higher detection rate of polyps with a diameter ≤5 mm than the PEG group (38.6% vs 18.8%, P = 0.004). A multivariate analysis showed that NaP and the withdrawal time of the colonoscope were independent factors associated with the detection of polyps with a diameter ≤5 mm. CONCLUSIONS: NaP is certainly not inferior to PEG. In fact, the results suggest that diminutive polyp detection using NaP might be superior to that using PEG.


Asunto(s)
Catárticos/administración & dosificación , Pólipos del Colon/diagnóstico , Colonoscopía/métodos , Fosfatos/administración & dosificación , Polietilenglicoles/administración & dosificación , Adulto , Anciano , Pólipos del Colon/patología , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego , Irrigación Terapéutica/métodos , Adulto Joven
17.
Int J Antimicrob Agents ; 39(4): 352-5, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22321702

RESUMEN

The third-line treatment regimen for Helicobacter pylori after failure of clarithromycin- and metronidazole-based therapies is not yet established. Sitafloxacin (STX) is a quinolone that possesses potent in vitro activity against H. pylori. In this study, the susceptibility of H. pylori isolates to STX was examined and the efficacy of STX-based triple therapy as a third-line regimen was evaluated. STX showed minimum inhibitory concentrations (MICs) of ≤1 µg/mL against all 100 H. pylori isolates, and the MIC(90) (MIC for 90% of the organisms) of STX was 5 log(2) dilutions lower than that of levofloxacin (LVX). The MIC(50) (MIC for 50% of the organisms) of STX against gyrA mutants was 0.12 µg/mL and was significantly lower than that of LVX (8 µg/mL). The activity of STX at pH 5.5 was significantly less than that at pH 7.0. In the clinical trial, 28 patients with two eradication failures were treated with STX-based triple therapy [rabeprazole 10 mg twice daily (b.i.d.), amoxicillin 750 mg b.i.d. and STX 100mg b.i.d. for 7 days]. The eradication rate was 75% using intention-to-treat analysis and 80% using per-protocol analysis. Two gyrA mutant strains were eradicated. Amongst participants, a low pepsinogen I/II ratio was associated with successful eradication. These results suggest that STX could be active against most clinical H. pylori isolates and that STX-based triple therapy is a promising and safe third-line therapy.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Fluoroquinolonas/farmacología , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Amoxicilina/farmacología , Antibacterianos/uso terapéutico , Girasa de ADN/genética , Erradicación de la Enfermedad/métodos , Femenino , Fluoroquinolonas/uso terapéutico , Genes Bacterianos , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Humanos , Concentración de Iones de Hidrógeno , Concentración 50 Inhibidora , Japón/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mutación , Pepsinógeno A/química , Pepsinógeno C/química , Estudios Prospectivos
18.
Biol Lett ; 8(3): 412-5, 2012 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-22219393

RESUMEN

Endosymbiotic bacteria of the genus Wolbachia induce diverse reproductive alterations in their insect hosts. Wolbachia (wSca) infecting the moth Ostrinia scapulalis causes unusual male killing, in which males (genotype: ZZ) selectively die during embryonic and larval development, whereas females (genotype: ZW), in turn, selectively die when cured of infection. To gain insight into the interaction between wSca and the host, we analysed phenotypic and genetic sexes of the embryos and larvae of normal, wSca-infected, and infected-and-cured O. scapulalis by diagnosing the sex-specifically spliced transcripts of Osdsx-a homologue of the sex-determining gene doublesex-and sex chromatin in interphase nuclei, respectively. It was observed that the female-type Osdsx was expressed in the infected male (ZZ) progenies destined to die, whereas the male-type Osdsx was expressed in the cured female (ZW) progenies destined to die. These findings suggest that (i) wSca, a male killer, carries a genetic factor that feminizes the male host, (ii) the sex-determining system of the host is degraded, and (iii) a mismatch between the genetic and phenotypic sexes underlies the sex-specific death.


Asunto(s)
Mariposas Nocturnas/crecimiento & desarrollo , Mariposas Nocturnas/microbiología , Wolbachia/fisiología , Animales , Proteínas de Unión al ADN/metabolismo , Femenino , Genotipo , Proteínas de Insectos/metabolismo , Japón , Larva/genética , Larva/crecimiento & desarrollo , Larva/metabolismo , Larva/microbiología , Masculino , Mariposas Nocturnas/genética , Mariposas Nocturnas/metabolismo , Isoformas de Proteínas/metabolismo , Diferenciación Sexual , Razón de Masculinidad , Simbiosis , Wolbachia/genética
19.
J Clin Gastroenterol ; 46(2): 124-9, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21959325

RESUMEN

BACKGROUND AND AIM: The technique of endoscopic submucosal dissection (ESD) was introduced to obtain en bloc specimens of large early gastrointestinal neoplasms. The drawback of ESD is its technical difficulty and, consequently, its higher rate of complication. In this multicenter study, we investigated the therapeutic outcomes of ESD in consecutive patients. METHODS: From January 2002 to December 2008, 485 early gastric neoplasms in 418 patients were consecutively treated by using ESD procedure performed by 6 endoscopists in 4 institutions in Tokyo. Demorgraphics, tumor location, therapeutic outcomes, and complication rates were analyzed. RESULTS: The rates of en bloc resection, complete en bloc resection, submucosal invasion, and piecemeal resection were 93.6%, 85.4%, 10.9%, and 5.4%, respectively. In multivariate analysis, the en bloc resection rate was independently lower in lesions in upper portion than in lower portion (P<0.01), lower in larger lesions (>30 mm, P<0.05; 20 to 30 mm, P<0.05), and lower in lesions with a scar (P<0.01). Delayed bleeding occurrence was independently high in larger lesions (>30 mm, P<0.01; 20 to 29 mm, P<0.01) than in small lesions (<20 mm). Institution and endoscopists were not risk factors of en bloc resection and complications CONCLUSIONS: ESD is an effective and safe therapy in the management of early gastric neoplasms when performed by well-trained endoscopists. Endoscopists should recognize the difficulty to perform ESD for en bloc resection of upper lesion, and the risk of delayed bleeding in cases of lesions >2 cm in size.


Asunto(s)
Adenocarcinoma/cirugía , Disección/efectos adversos , Endoscopía Gastrointestinal/efectos adversos , Mucosa Gástrica/cirugía , Neoplasias Gástricas/cirugía , Adenocarcinoma/patología , Anciano , Disección/métodos , Detección Precoz del Cáncer , Endoscopía Gastrointestinal/métodos , Estudios de Factibilidad , Femenino , Mucosa Gástrica/patología , Humanos , Complicaciones Intraoperatorias , Japón , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias , Neoplasias Gástricas/patología , Resultado del Tratamiento
20.
Hepatogastroenterology ; 59(113): 108-11, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-21940364

RESUMEN

BACKGROUND/AIMS: We aimed to investigate the association between colorectal polyp detection rates and withdrawal times, and also to investigate diverticulum detection rates as a counterpart lesion. METHODOLOGY: Thirteen trainee colonoscopists were characterized by their mean withdrawal time for normal colon. A total of 2,314 colonoscopies were analyzed. RESULTS: The mean withdrawal times ranged from 6.5 to 10.4 minutes among colonoscopists. Polyp detection rates in individual endoscopists ranged between 36.5% and 60.0%. When stratified by the hood use, a significant association was shown when the hood was not used (p=0.03), whereas no association was found when the hood used. On the other hand, diverticulum detection rates varied from 20.7% to 43.2%. A strong association was shown only when the hood was not used (p=0.009). CONCLUSIONS: An association between the polyp or diverticulum detection rate and the withdrawal time was observed when the transparent hood was not attached, and mainly on the right-side colon.


Asunto(s)
Pólipos del Colon/patología , Colonoscopía , Divertículo del Colon/patología , Pólipos Intestinales/patología , Enfermedades del Recto/patología , Anciano , Competencia Clínica , Colonoscopios , Colonoscopía/instrumentación , Diseño de Equipo , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Tiempo
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