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1.
Phys Rev Lett ; 124(25): 252501, 2020 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-32639790

RESUMEN

Transverse single-spin asymmetries of very forward neutral pions generated in polarized p+p collisions allow us to understand the production mechanism in terms of perturbative and nonperturbative strong interactions. During 2017, the RHICf Collaboration installed an electromagnetic calorimeter in the zero-degree region of the STAR detector at the Relativistic Heavy Ion Collider (RHIC) and measured neutral pions produced at pseudorapidity larger than 6 in polarized p+p collisions at sqrt[s]=510 GeV. The large nonzero asymmetries increasing both in longitudinal momentum fraction x_{F} and transverse momentum p_{T} have been observed at low transverse momentum p_{T}<1 GeV/c for the first time, at this collision energy. The asymmetries show an approximate x_{F} scaling in the p_{T} region where nonperturbative processes are expected to dominate. A non-negligible contribution from soft processes may be necessary to explain the nonzero neutral pion asymmetries.

2.
Scand J Rheumatol ; 48(3): 218-224, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30394816

RESUMEN

OBJECTIVE: We aimed to describe the clinical characteristics and treatment course of hypertrophic pachymeningitis (HPM) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We retrospectively analysed 15 patients (11 men and four women). HPM was diagnosed based on thickening and enhancing of the brain and/or spinal dura mater on gadolinium-enhanced magnetic resonance imaging (MRI) T1 sequence. RESULTS: The median age at HPM onset was 60 years. Headache and cranial nerve impairment were observed in 14 and 10 patients, respectively. Otitis media and/or mastoiditis were found as complications of AAV in 11 patients. Fourteen patients were classified as having granulomatosis with polyangiitis (GPA). Single-positive myeloperoxidase-ANCA, single-positive proteinase 3-ANCA, and double-positive ANCA were identified in seven patients, five patients, and one patient, respectively. With MRI, thickening of the dura mater in the cranial fossa and tentorium cerebelli was found in 10 and eight patients, respectively. For remission induction, all patients were treated with corticosteroids, and immunosuppressants were added in 10 patients. Dura mater thickening partially improved in all patients, and cranial neuropathy completely remitted in eight patients. In a median follow-up of 43 months, four patients had HPM relapse and underwent reinduction therapy. All six patients treated with cyclophosphamide at initial therapy did not relapse. CONCLUSIONS: HPM was mostly associated with patients with GPA with otitis media and/or mastoiditis having either type of ANCA serology. Treatment with corticosteroids with or without immunosuppressants was effective. However, HPM relapse occasionally occurred, especially when cyclophosphamide was not used in initial treatment.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Encéfalo/diagnóstico por imagen , Duramadre , Granulomatosis con Poliangitis , Inmunosupresores/uso terapéutico , Meningitis , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Enfermedades de los Nervios Craneales/diagnóstico , Enfermedades de los Nervios Craneales/etiología , Duramadre/diagnóstico por imagen , Duramadre/patología , Femenino , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Humanos , Hipertrofia , Japón , Imagen por Resonancia Magnética/métodos , Masculino , Meningitis/diagnóstico , Meningitis/tratamiento farmacológico , Meningitis/inmunología , Meningitis/fisiopatología , Persona de Mediana Edad , Inducción de Remisión
3.
Curr Oncol ; 24(4): e328-e332, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28874903

RESUMEN

Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients. Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published). Because the imids are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed hsr when receiving previous lines of imids. As a patient's advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients. Intervention with the use of a rapid desensitization program (rdp) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient's safety will ensure a smooth transition into pomalidomide treatment. A hsr can be either related or non-related to immunoglobulin E. As imids become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo rdp safely. Patients enjoy a good quality of life and clinical response after the rdp procedure.

4.
Curr Oncol ; 23(4): e355-61, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27536184

RESUMEN

BACKGROUND: Venous thromboembolism (vte) is a recognized complication in patients treated with asparaginase-containing chemotherapy regimens; the optimal preventive strategy is unclear. We assessed the safety and efficacy of prophylaxis using low-dose low molecular weight heparin in adult patients with acute lymphoblastic leukemia in complete remission treated with an asparaginase-based post-remission chemotherapy regimen. METHODS: As part of the intensification phase of the Dana-Farber Cancer Institute 91-01 regimen, asparaginase was administered weekly to 41 consecutive patients for 21-30 weeks; these patients also received prophylaxis with enoxaparin 40 mg daily (60 mg for patients ≥80 kg). Outcomes were assessed against outcomes in a comparable cohort of 99 patients who received the same chemotherapy regimen without anticoagulation prophylaxis. RESULTS: The overall rate of symptomatic venous thrombosis was not significantly different in the prophylaxis and non-prophylaxis cohorts (18.92% and 21.74% respectively). Among patients receiving prophylaxis, vte occurred in higher proportion in those who weighed at least 80 kg (42.86% vs. 4.35%, p = 0.0070). No major bleeding complications occurred in the prophylaxis group (minor bleeding: 8.1%). CONCLUSIONS: Prophylaxis with low-dose enoxaparin during the intensification phase was safe, but was not associated with a lower overall proportion of vte.

5.
Curr Oncol ; 22(5): e357-63, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26628876

RESUMEN

BACKGROUND: Keratoconjunctivitis sicca from chronic graft-versus-host disease (cgvhd) after allogeneic stem cell transplantation is common, leading to severe corneal damage and blindness if not treated. We retrospectively examined the efficacy and safety of pooled human albumin eye drops (haeds) for symptom relief in 40 stem-cell transplantation patients after other alternatives had failed. METHODS: The Common Terminology Criteria for Adverse Events (version 4.0) and the cgvhd grading scale were used to compare response in the patients during January 2000 and July 2013. In addition, on days 1 and 30, the haeds were subjected to quality assurance testing for sterility, oncotic pressure, albumin measurement, viscosity, pH, and purity by protein electrophoresis. RESULTS: Use of haeds resulted in symptom relief for 37 patients (92.5%); 3 patients (7.5%) failed to improve with use of haeds (p ≤ 0.0001). Of the 37 patients having symptom relief, 7 (19%) improved from grade 3 to no dry eye symptoms. Proportionately, post-treatment symptom improvement by two grade levels, from 3 to 1 (70%), was significantly higher than improvement by one grade level, from 3 to 2 (11%) or from 2 to 1 (19%, p ≤ 0.0001). Time to symptom relief ranged from 2 weeks to 28 weeks. Of the 40 patients, 38 (95%) had no adverse reactions. Days 1 and 30 quality assurance testing results were equivalent. CONCLUSIONS: Complications of keratoconjunctivitis sicca were well managed and well tolerated with haeds when other remedies failed. Quality assurance testing confirmed that haeds were safe and stable in extreme conditions.

6.
Eur J Pain ; 28(6): 1018-1028, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38318653

RESUMEN

BACKGROUND: Oscillatory activities observed in multiple regions are closely associated with the experience of pain. Specifically, oscillatory activities within the theta- and beta-frequency bands, observed in the left dorsolateral prefrontal cortex (DLPFC), have been implicated in pain perception among healthy individuals and those with chronic pain. However, their physiological significance remains unclear. METHODS: We explored the modulation of pain perception in healthy individuals by theta- and beta-band transcranial alternating current stimulation (tACS) over the left DLPFC and examined the relationship between the modulation effect and magnitude of the electric field elicited by tACS in the left DLPFC using computational simulation. RESULTS: Our findings revealed that both theta- and beta-tACS increased the heat pain threshold during and after stimulation. Notably, the simulated electric field magnitude in the left DLPFC exhibited an inverted U-shaped relationship with the pain modulation effect for theta-tACS. CONCLUSIONS: Our study findings suggested that there would be an optimal electric field strength to produce a high analgesic effect for theta-tACS. SIGNIFICANCE: The application of theta- and beta-tACS interventions targeting the left DLPFC might facilitate the treatment of chronic pain. Furthermore, the attainment of effective pain modulation via theta-tACS over the DLPFC warrants the use of optimal stimulus intensity.


Asunto(s)
Percepción del Dolor , Umbral del Dolor , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Masculino , Femenino , Percepción del Dolor/fisiología , Adulto , Adulto Joven , Umbral del Dolor/fisiología , Ritmo Teta/fisiología , Corteza Prefontal Dorsolateral/fisiología , Ritmo beta/fisiología , Dolor Crónico/terapia , Dolor Crónico/fisiopatología , Manejo del Dolor/métodos
8.
J Small Anim Pract ; 63(11): 843-847, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36058894

RESUMEN

A 9-year-old spayed female crossbreed cat with chief complaints of anorexia and hypersalivation had high serum concentrations of ammonia and fasting and postprandial total bile acid. Therefore, she was referred to our hospital. On the first evaluation, haematology, serum chemistry, radiography and ultrasonography findings suggested that she had a congenital portosystemic shunt. CT revealed a shunt vessel from the left gastric vein to the left pulmonary vein. During median celiotomy and sternotomy, gross findings and mesenteric portography revealed abnormal vessel shunting from the left gastric vein to the left pulmonary vein. Complete ligation of the shunt vessel was achieved. She recovered without any complications. Postoperative serum chemistry revealed that ammonia and total bile acid levels decreased to within the reference intervals. This report is the first to describe the clinical features and surgical outcome of a cat with a congenital portopulmonary shunt.


Asunto(s)
Amoníaco , Portografía , Femenino , Gatos , Animales , Derivación Portosistémica Quirúrgica/veterinaria , Vena Porta/anomalías , Ácidos y Sales Biliares , Sistema Porta/diagnóstico por imagen , Sistema Porta/cirugía , Sistema Porta/anomalías
9.
J Small Anim Pract ; 63(12): 904-910, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36226325

RESUMEN

Two dogs with anorexia and rapid weight loss were referred to our hospital due to a right renal mass and several pulmonary nodules. Both dogs underwent needle core biopsy of the mass, followed by transarterial chemoembolisation of the renal mass. A catheter was inserted from the femoral artery and advanced into the right renal artery. A suspension of carboplatin (100 mg/m2 ) and equivalent lipiodol was administered via the inserted multipurpose catheter. Immediately after, under fluoroscopic guidance, pulse injections of small amounts of gelatin particles (diameter 1 mm) dissolved in iohexol were administered until complete embolisation of the renal artery. Histopathologic diagnosis was renal cell carcinoma in both dogs. Clinical signs improved for 134 and 358 days after transarterial chemoembolisation. In addition, postoperative radiographs demonstrated a decrease in the tumour size. The dogs died 215 and 525 days after the initial evaluation, respectively. As a palliative treatment, transarterial chemoembolisation might help reduce the tumour volume and improve the quality of life in dogs with renal cell carcinoma and distant metastases.


Asunto(s)
Carcinoma Hepatocelular , Carcinoma de Células Renales , Quimioembolización Terapéutica , Enfermedades de los Perros , Neoplasias Renales , Neoplasias Hepáticas , Neoplasias Pulmonares , Perros , Animales , Quimioembolización Terapéutica/veterinaria , Carcinoma Hepatocelular/veterinaria , Neoplasias Hepáticas/veterinaria , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/veterinaria , Cuidados Paliativos , Calidad de Vida , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/veterinaria , Neoplasias Renales/terapia , Neoplasias Renales/veterinaria , Resultado del Tratamiento , Enfermedades de los Perros/terapia
10.
Clin Exp Dermatol ; 35(4): e123-6, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19925486

RESUMEN

Schnitzler's syndrome is a rare disorder of unknown aetiology characterized by a chronic urticarial eruption, intermittent fever and monoclonal gammopathy. We encountered an interesting patient with this syndrome, who had been misdiagnosed for 10 years as having Sweet's syndrome because of the histopathological picture, which was a prominent perivascular and interstitial neutrophilic infiltrate in the dermis with leucocytoclasia but without vasculitis. An urticarial eruption with this histopathological feature has recently been categorized as neutrophilic urticarial dermatosis, and it is strongly indicative of an associated systemic disease, mainly Schnitzler's syndrome and other inflammatory diseases. We therefore need to be cautious not to confuse Schnitzler's syndrome with Sweet's syndrome. Further, the serum interleukin (IL)-6 levels, but not those of other cytokines and chemokines, correlated with the disease activity in our patient, suggesting that IL-6 may be involved in some of the disease processes, including neutrophil infiltration.


Asunto(s)
Infiltración Neutrófila , Paraproteinemias/diagnóstico , Síndrome de Sweet/diagnóstico , Urticaria/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Paraproteinemias/patología , Síndrome , Urticaria/patología
11.
Andrology ; 7(5): 644-653, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30927342

RESUMEN

BACKGROUND: Spermatozoa become competent for fertilization during transit through the epididymis. As spermatozoa from the proximal caudal epididymis can fertilize eggs, proteins from the caput and corpus epididymis are required for sperm maturation. OBJECTIVES: Microarray analysis identified that more than 17,000 genes are expressed in the epididymis; however, few of these genes demonstrate expression restricted to the epididymis. To analyze epididymis-enriched gene function in vivo, we generated knockout (KO) mutations in nine genes that are abundantly expressed in the caput and corpus region of the epididymis. MATERIALS AND METHODS: KO mice were generated using the CRISPR/Cas9 system. The histology of the epididymis was observed with hematoxylin and eosin staining. KO males were caged with wild-type females for 3-6 months to check fertility. RESULTS: We generated individual mutant mouse lines having indel mutations in Pate1, Pate2, or Pate3. We also deleted the coding regions of Clpsl2, Epp13, and Rnase13, independently. Finally, the 150 kb region encoding Gm1110, Glb1l2, and Glb1l3 was deleted to generate a triple KO mouse line. Histology of the epididymis and sperm morphology of all KO lines were comparable to control males. The females mated with these KO males delivered pups at comparable numbers as control males. DISCUSSION AND CONCLUSION: We revealed that nine genes abundantly expressed in the caput and corpus epididymis are dispensable for sperm function and male fecundity. CRISPR/Cas9-mediated KO mice generation accelerates the screening of epididymis-enriched genes for potential functions in reproduction.


Asunto(s)
Epidídimo/metabolismo , Fertilidad/genética , Proteínas de la Membrana/genética , Espermatozoides/metabolismo , Animales , Sistemas CRISPR-Cas , Técnicas de Inactivación de Genes , Masculino , Ratones , Ratones Noqueados , Maduración del Esperma/fisiología , Motilidad Espermática/genética
12.
Rheumatology (Oxford) ; 47(6): 815-20, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18397956

RESUMEN

OBJECTIVE: IL-19 is a novel cytokine of the IL-10 family. In this study, we sought to examine whether IL-19 plays a role in the pathogenesis of RA. METHODS: Expression of IL-19, IL-20 receptor 1 (IL-20R1) and IL-20R2 was examined by RT-PCR and immunohistochemical analysis in rheumatoid synovium. The effects of IL-19 on synovial cells established from rheumatoid synovium (RASCs), with regard to IL-6 production and signal transducers and activators of transcription3 (STAT3) activation, were examined by ELISA and western blot analysis, respectively. The effect of IL-19 on RASC apoptosis was examined by Hoechst staining, flow cytometry analysis of annexin V binding and caspase-3 activity. RESULTS: IL-19, IL-20R1 and IL-20R2 mRNA were detected by RT-PCR in synovial tissues from RA patients. Immunohistochemical analysis showed IL-19 was predominantly expressed in the hyperplastic lining layers of RA synovial tissues. The majority of IL-19-positive cells were vimentin-positive and CD68-positive synovial cells, serving as markers of fibroblasts and macrophages, respectively. IL-20R1 and IL-20R2 (IL-20Rs) were expressed in both the lining and sublining layers of RA synovium. In RASC, IL-19 was induced by lipopolysaccharide stimulation and constitutive expression of IL-20Rs was observed, suggesting IL-19 has an autocrine action. In terms of this function, IL-19 induced STAT3 activation and increased IL-6 production by RASC above the medium control. Moreover, IL-19 significantly reduced RASC apoptosis induced by serum starvation. CONCLUSIONS: These data suggest that IL-19, produced by synovial cells, promotes joint inflammation in RA by inducing IL-6 production and decreasing synovial cell apoptosis.


Asunto(s)
Artritis Reumatoide/inmunología , Interleucinas/metabolismo , Receptores de Interleucina/metabolismo , Membrana Sinovial/inmunología , Apoptosis/inmunología , Artritis Reumatoide/patología , Caspasa 3/metabolismo , Células Cultivadas , Humanos , Hiperplasia/inmunología , Interleucina-6/biosíntesis , Interleucinas/inmunología , Proteínas Recombinantes/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/inmunología , Membrana Sinovial/patología
13.
Cancer Res ; 56(18): 4205-12, 1996 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-8797593

RESUMEN

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we synthesized two bispecific antibodies (BsAbs), MUC1 x CD3 BsAb constructed with MUSE11 (anti-MUC1 tumor antigen) and OKT-3 (anti-CD3), and MUC1 x CD28 BsAb constructed with MUSE11 and 15E8 (anti-CD28) antibodies. These two BsAbs reacted well with both MUC1-positive target tumor cells and effector lymphokine-activated killer (LAK) cells. Investigation of in vitro cytotoxicity [3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide assay] revealed that the MUC1 x CD3 BsAb could antigen-specifically enhance the cytotoxicity of LAK cells. Addition of the two BsAbs (MUC1 x CD3 BsAb plus MUC1 x CD28 BsAb) in vitro resulted in a 60% cytotoxicity, similar to that obtained with BsAb (MUC1 x CD3) alone. Interleukin 12-induced LAK cells demonstrated far greater cytotoxicity (50%) than their interleukin 2-induced counterparts (LAK cells), and this was also enhanced by the BsAbs. When 2 x 10(7) LAK cells sensitized with both kinds of BsAbs were administered four times i.v. to BDC-grafted severe combined immunodeficient mice (tumor size 5 mm in diameter), inhibition of tumor growth was observed. Thus, BsAb-LAK therapy for control of BDC warrants clinical trials.


Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Neoplasias de los Conductos Biliares/terapia , Citotoxicidad Inmunológica , Inmunoterapia , Mucina-1/inmunología , Animales , Antígenos de Neoplasias/inmunología , Neoplasias de los Conductos Biliares/inmunología , Neoplasias de los Conductos Biliares/patología , Complejo CD3/inmunología , Línea Celular , Citometría de Flujo , Humanos , Interleucina-12/inmunología , Interleucina-2/inmunología , Células Asesinas Activadas por Linfocinas/inmunología , Ratones , Ratones SCID , Muromonab-CD3/inmunología , Factores de Tiempo , Trasplante Heterólogo
14.
Cancer Res ; 58(13): 2838-43, 1998 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-9661899

RESUMEN

To reinforce cytotoxic activity and the targeting ability of lymphokine-activated killer cells with a T-cell phenotype (T-LAK) for adoptive immunotherapy against human bile duct carcinoma (BDC), staphylococcal enterotoxin A (SEA) was conjugated chemically with MUSE11 monoclonal antibody (MUSE11 mAb), directed to the MUC1 antigen, using N-succinimidyl 3-(2-pyridyldithio) propionate and 2-iminothiolane HCl. Both SEA-conjugated MUSE11 mAb (SEA-MUSE11) and the F(ab')2 of MUSE11 mAb (SEA-F(ab')2) showed significant enhancement of T-LAK cell tumor neutralization for MUC1 positive-target tumor cells, even with a concentration of 0.01 microg/ml at an E:T ratio of 5:1 in vitro. In this in vitro test, MUC1-positive BDC cells were observed to attach to surrounding T-LAK cells in the presence of SEA-MUSE11 or SEA-F(ab')2. Remarkable tumor growth inhibition was observed in BDC-grafted severe combined immunodeficient mice to which 2 x 10(7) T-LAK cells preincubated with 2 microg of SEA-MUSE11 or SEA-F(ab')2, together with recombinant interleukin 2 (500 IU), were administered i.v. for 4 consecutive days, when tumor size was 5 mm in diameter. These results point to a promising adoptive immunotherapy for patients with BDC.


Asunto(s)
Neoplasias de los Conductos Biliares/terapia , Enterotoxinas/uso terapéutico , Inmunoterapia Adoptiva/métodos , Inmunotoxinas/uso terapéutico , Células Asesinas Activadas por Linfocinas , Mucina-1/inmunología , Superantígenos/uso terapéutico , Animales , Anticuerpos Monoclonales/uso terapéutico , Adhesión Celular , Humanos , Ratones , Ratones SCID , Trasplante de Neoplasias
15.
J Mol Biol ; 304(3): 397-410, 2000 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-11090282

RESUMEN

Oxidative biodegradation of aromatic compounds by bacteria usually begins with hydroxylation of the aromatic ring by multi-component dioxygenases like benzene dioxygenase, biphenyl dioxygenase, and others. These enzymes are composed of ferredoxin reductase, ferredoxin, and terminal oxygenase. Reducing equivalents that originate from NADH are transferred from ferredoxin reductase to ferredoxin and, in turn, to the terminal oxygenase, thus resulting in the activation of a dioxygen. BphA4 is the ferredoxin reductase component of biphenyl dioxygenase from Pseudomonas sp. strain KKS102. The amino acid sequence of BphA4 exhibits significant homology with the putidaredoxin reductase of the cytochrome P450cam system in Pseudomonas putida, as well as with various other oxygenase-coupled NADH-dependent ferredoxin reductases (ONFRs) of bacteria. To date, no structural information has been provided for the ferredoxin reductase component of the dioxygenase systems. In order to provide a structural basis for discussing the mechanism of electron transport between ferredoxin reductase and ferredoxin, crystal structures of BphA4 and its NADH complex were solved. The three-dimensional structure of BphA4 is different from those of ferredoxin reductases whose structures have already been determined, but adopts essentially the same fold as the enzymes of the glutathione reductase (GR) family. Also the three-dimensional structure of the first two domains of BphA4 adopts a fold similar to that of adrenodoxin reductase (AdR) in the mitochondrial cytochrome P450 system. Comparing the amino acid sequence with what is known of the three-dimensional structure of BphA4 strongly suggests that the other ONFRs have secondary structural features that are similar to that of BphA4. This analysis of the crystal structures of BphA4 suggests that Lys53 and Glu159 seem to be involved in the hydride transfer from NADH to FAD. Since the amino acid residues around the active site, some of which seem to be important to electron transport, are highly conserved among ONFRs, it is likely that the mechanism of electron transport of BphA4 is quite applicable to other ONFRs.


Asunto(s)
Proteínas Hierro-Azufre , Oxidorreductasas/química , Oxigenasas/química , Pseudomonas/enzimología , Secuencia de Aminoácidos , Factor Inductor de la Apoptosis , Sitios de Unión , Cristalografía por Rayos X , Transporte de Electrón , Evolución Molecular , Flavina-Adenina Dinucleótido/química , Flavina-Adenina Dinucleótido/metabolismo , Flavoproteínas/química , Glutatión Reductasa/química , Humanos , Proteínas de la Membrana/química , Modelos Moleculares , Datos de Secuencia Molecular , NAD/química , NAD/metabolismo , Oxidorreductasas/metabolismo , Oxigenasas/metabolismo , Unión Proteica , Estructura Cuaternaria de Proteína , Estructura Terciaria de Proteína , Alineación de Secuencia
16.
Plant Physiol ; 106(3): 971-976, 1994 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12232377

RESUMEN

Growth of squash (Cucurbita maxima Duch.) roots was significantly inhibited by 1 mM AlCl3 as early as 1 h after the treatment. The growth inhibition was confined to the elongating zone (1-6 mm from the root tip). Chemical analysis of cell-wall polysaccharides from roots revealed that aluminum increased pectin, hemi-cellulose, and cellulose contents after 3 h of treatment. The effect of aluminum on pectin content was found in the elongating zone including the root tip, whereas change in cellulose content was confined to only nonelongating zones. Hemicellulose content increased in all of the regions along the root axis. The increase in the pectin fraction was due to the increases in uronic acids, galactose, and arabinose constituents, whereas hemicellulose content changed due to increases in glucose, xylose, galactose, and arabinose. The results clearly indicate that aluminum rapidly reduced squash root growth by inhibiting cell elongation and altering metabolism of cell-wall polysaccharides in the nonelongating zone as well as in the elongating zone.

17.
Diabetes Care ; 17(2): 107-14, 1994 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8137680

RESUMEN

OBJECTIVE: To understand the interrelationship of coronary artery disease (CAD) risk factors including hyperlipidemia, hypertension, and glucose intolerance to prevent and better manage this disease. RESEARCH DESIGN AND METHODS: We performed a 100-g oral glucose tolerance test in 2,113 subjects, and we evaluated their plasma lipid levels, blood pressure (BP), and plasma glucose and plasma insulin responses. RESULTS: Multiple regression analysis demonstrated a significant relationship of either BP, plasma triglyceride (TG), or high-density lipoprotein (HDL) cholesterol levels to plasma insulin and glucose response after the glucose load. Plasma cholesterol levels were related only to the plasma glucose response. In subjects matched for age, sex, and body mass index (BMI) with hyperinsulinemia or normoinsulinemia, the hyperinsulinemic subjects had a significantly higher mean BP and plasma TG level than the normoinsulinemic subjects (128.8/82.3 vs. 122.9/79.3 mmHg and 172.1 vs. 119.4 mg/dl), and the HDL-cholesterol level was significantly lower (43.9 vs. 47.8 mg/dl). Furthermore, subjects matched for age, sex, and BMI with glucose intolerance had a higher mean BP (128.4/81.8 vs. 123.5/78.7 mmHg) and higher plasma TG level (154.2 vs. 123.0 mg/dl) than those without glucose intolerance. CONCLUSIONS: Based on these findings, subjects with hyperinsulinemia or glucose intolerance should be carefully managed to prevent CAD, because they have more numerous and more severe risk factors than subjects with normal plasma insulin levels or subjects without glucose intolerance.


Asunto(s)
Enfermedad Coronaria/epidemiología , Intolerancia a la Glucosa/complicaciones , Prueba de Tolerancia a la Glucosa , Hiperinsulinismo/complicaciones , Glucemia/metabolismo , Presión Sanguínea , Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Intolerancia a la Glucosa/diagnóstico , Intolerancia a la Glucosa/fisiopatología , Humanos , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/fisiopatología , Japón/epidemiología , Lípidos/sangre , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo , Triglicéridos/sangre
18.
FEBS Lett ; 476(3): 266-71, 2000 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-10913626

RESUMEN

The most predominant co-stimulation pathway, which is critical for T cell activation and proliferation, is the CD28-B7 pathway. The anti-CD28 monoclonal antibody (mAb) also provides a co-stimulatory signal to T cells. In order to construct a functional Fv fragment (complex of VH and VL domains) of anti-CD28 antibody using a bacterial expression system, cDNA encoding the variable regions of immunoglobulin from 15E8 hybridoma cells was cloned and expressed in Escherichia coli. The Fv fragment was obtained as a soluble protein from the periplasmic fraction and showed a binding pattern similar to parental IgG. The Fv fragment induced proliferation of peripheral blood mononuclear cells in the presence of anti-CD3 or anti-CD2 mAb and enhanced anti-tumor activity of anti-MUC1x(anti)-CD3 bispecific antibody when tested with lymphokine-activated killer cells with T cell phenotype. Thus, the anti-CD28 Fv fragment will be promising not only for the study of co-stimulation, but also for cancer immunotherapy.


Asunto(s)
Antígenos CD28/inmunología , Fragmentos de Inmunoglobulinas/inmunología , Linfocitos T/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Secuencia de Bases , División Celular , Clonación Molecular , Citotoxicidad Inmunológica , ADN Recombinante/genética , Escherichia coli/genética , Humanos , Hibridomas , Fragmentos de Inmunoglobulinas/genética , Inmunoterapia , Células Asesinas Activadas por Linfocinas/inmunología , Activación de Linfocitos , Ratones , Datos de Secuencia Molecular , Linfocitos T/citología , Células Tumorales Cultivadas
19.
Neurology ; 39(12): 1615-8, 1989 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2586778

RESUMEN

We studied the onset of preparatory postural responses and subsequent voluntary movements by measuring soleus muscle activities in the standing position in 20 patients with Parkinson's disease. We measured the postural response in preparing to rise on tiptoe as the onset of the premotion silent period (PMSP). Our patients showed no delay when compared with age-matched healthy controls, but did show a significant delay in the onset of voluntary movement. The elongated PMSP (increased duration of the preparatory postural adjustments) was related to the severity of bradykinesia. Results indicate that the conventional reaction time is increased in patients with Parkinson's disease, even though there is no delay of central processing for the preparation of voluntary movements, and that there is bradykinesia of involuntary postural movements.


Asunto(s)
Movimiento , Músculos/fisiopatología , Enfermedad de Parkinson/fisiopatología , Adulto , Anciano , Electromiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción , Valores de Referencia
20.
Am J Cardiol ; 60(7): 555-9, 1987 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-3307369

RESUMEN

The populations of T cells were studied in 46 patients with Kawasaki disease, separated into 2 groups: group I--11 patients with coronary aneurysms; and group II--35 patients with normal coronary arteries. Patients from both groups with early acute illness, before day 5, had a significant reduction in the population of OKT3+ (p less than 0.001), OKT4+ (p less than 0.02) and OKT8+ cells (p less than 0.002), but normal OKT4/OKT8 ratios compared with age-matched control subjects. These abnormal values quickly returned to normal levels during week 2 in patients with normal coronary arteries. In contrast, patients in whom coronary aneurysms developed within 3 weeks of the onset had an imbalance between OKT4 and OKT8 during week 2, characterized by a decrease in the number of OKT8+ cells and an increase in the number of OKT4+ cells, resulting in a high OKT4/OKT8 ratio (p less than 0.01). Three patients in whom large coronary aneurysms developed had ratios higher than 4.50. Follow-up analysis of T-cell subsets from individual patients with coronary aneurysms showed that the OKT4/OKT8 ratio during the acute stage was reduced during the convalescent stage (p less than 0.005). In contrast, the ratio in patients with normal coronary arteries was normal during the course of the illness. These observations suggest that an immune regulatory process operating in coronary aneurysm formation is present.


Asunto(s)
Aneurisma Coronario/inmunología , Síndrome Mucocutáneo Linfonodular/inmunología , Linfocitos T/clasificación , Anticuerpos Monoclonales , Separación Celular , Preescolar , Aneurisma Coronario/etiología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Lactante , Síndrome Mucocutáneo Linfonodular/complicaciones
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