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1.
Rhinology ; 60(3): 177-187, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35233583

RESUMO

BACKGROUND: Whether endoscopic surgery for sellar/parasellar disease causes significant deficits in olfactory function remains unclear. We aimed to systematically review the olfactory outcomes in such settings based on the evidence up to date. METHODS: PubMed, EMBASE, and CENTRAL were searched through February 1, 2021. Included studies were limited to endoscopic surgery for sellar/parasellar disease with follow-up olfactory function measured by standardized olfactory testing methods or subjective assessment. The primary outcome was the change in olfactory function after surgery assessed by standardized olfactory testing methods. The secondary outcome was the change in subjective olfactory function. Random-effects model was used in obtaining combine effects. Study quality was assessed using the Newcastleâ€"Ottawa scale. Sensitivity analysis was carried out using the leave-one-out approach, and publication bias was assessed using Egger's test. RESULTS: The results show no significant difference in olfaction assessed by standardized olfactory testing methods at 1-3 months post-surgery (880 patients in 16 studies) or at 6-12 months post-surgery (1320 patients in 16 studies) compared to pre-surgery, whereas a significantly lower subjective olfaction at 3 months was observed. In addition, the lack of significant change in olfaction as assessed by standardized olfactory testing methods was observed regardless of whether patients were treated with or without the nasoseptal flap (NSF) harvesting. Heterogeneity and publication bias were observed, whereas sensitivity analysis showed the meta-analysis results are robust. CONCLUSION: The findings of this updated systematic review and meta-analysis support the conclusion that endoscopic surgery for sellar and parasellar pathology may pose no greater risk of olfactory dysfunction. In addition, the current evidence does not support there is an increased risk of diminished olfaction among patients treated with NSF during surgery.


Assuntos
Transtornos do Olfato , Olfato , Humanos , Transtornos do Olfato/etiologia , Resultado do Tratamento , Endoscopia/métodos , Retalhos Cirúrgicos
2.
Cell Death Discov ; 2: 16065, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27752362

RESUMO

Tanshinone IIA (Tan IIA), a constituent of the traditional medicinal plant Salvia miltiorrhiza BUNGE, has been reported to possess anticancer activity through induction of apoptosis in many cancer cells. Surprisingly, the present study finds that Tan IIA simultaneously causes apoptosis and necroptosis in human hepatocellular carcinoma HepG2 cells. We further find that apoptosis can be converted to necroptosis by pan-caspase inhibitor Z-VAD-fmk, and the two death modes can be blocked by necroptotic inhibitor necrostatin-1. The underlying mechanisms are revealed by analysis of the signaling molecules using western blotting. In control cells, FLICE inhibitory protein in short form (FLIPS) is expressed in relatively high levels and binds to caspase 8 in ripoptosome, which supposedly sustains cell survival. However, in Tan IIA-treated cells, FLIPS is down-regulated and may thus cause homodimer formation of cleaved caspase 8, cleavage of receptor-interacting serine/threonine-protein kinases 1, 3 (RIP1, RIP3), and mixed-lineage kinase domain-like (MLKL), in turn leads to cell apoptosis. In parallel, Tan IIA causes necroptosis by forming a suggested necrosomal complex composed of RIP1/RIP3. Regarding the inhibitors, z-VAD-fmk diminishes the cleaved caspase 8, RIP1, RIP3, and MLKL induced by Tan IIA, and reconstructs the ripoptosome complex, which marks cells moving from apoptosis to necroptosis. Nec-1 recovers the Tan IIA down-regulated FLIPS, consequently causes FLIPS to form heterodimer with caspase 8 and thus block apoptosis. Meanwhile, cleaved forms of RIP1 and RIP3 were observed preventing necroptosis. Intriguingly, the cytotoxicity of tumor necrosis factor-related apoptosis-inducing ligand to HepG2 cells is enhanced by Tan IIA in a pilot study, which may be attributed to low FLIPS levels induced by Tan IIA. In short, Tan IIA simultaneously induces both Nec-1 inhibition and FLIPS regulation-mediated apoptosis/necroptosis, which has not been previously documented. Moreover, the involvement of the cleavage type of MLKL in executing necroptosis warrants further investigation.

3.
Eur J Surg Oncol ; 37(1): 18-24, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21093206

RESUMO

AIMS: The purpose of this study was to clarify the prognostic significance of triple-negative breast cancer (TNBC) with a tumor size ≤ 1 cm. MATERIALS AND METHODS: Patients with primary operable breast cancer with a tumor size ≤ 1 cm were enrolled at Changhua Christian Hospital and National Cheng-Kung University Hospital. Tumors negative for ER, PR, and HER-2 were classified as TNBCs and compared with tumors with any receptor positivity (non-TNBC) for disease-free survival (DFS) and cancer-specific survival (CSS). RESULTS: From 1995 to 2006, a total of 377 patients with tumor size ≤ 1 cm were enrolled. Compared with non-TNBC patients, TNBC patients with a tumor size ≤ 1 cm as a whole or in a lymph node-positive subgroup were not associated with a poorer 5-year DFS and CSS. In lymph node-negative patients (pT1a-bN0M0), TNBC was associated with a poorer 5-year CSS but not DFS. Compared with the hormone receptor-positive, HER-2-negative subgroup, TNBC was associated with poorer DFS and CSS. In the multivariate Cox regression hazard analysis, lymph node invasion was the most important cause of disease recurrence and cancer-specific death. CONCLUSION: TNBC is very likely an independent risk factor in small (≤1 cm) node-negative invasive breast cancer. With tumors 1 cm and smaller, lymph node invasion was the single most important prognostic factor.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Adulto Jovem
4.
Histopathology ; 53(5): 554-60, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18983464

RESUMO

AIMS: Grap2 and cyclin-D interacting protein (GCIP) is a putative tumour suppressor in human cancer. The aim was to investigate its prognostic significance in human breast carcinoma. METHODS AND RESULTS: Immunohistochemical analysis of breast carcinoma specimens from 107 female patients was performed. Decreased cytoplasmic expression of GCIP was detected in breast carcinomas compared with normal ductal epithelium (P < 0.001). Higher GCIP scores were observed in patients with lower histological grade, mucinous carcinomas and better clinical outcome (P < 0.05). Disease-free survival was significantly longer in patients with high GCIP scores than in those with low GCIP scores (P = 0.010). However, GCIP expression was independent of the status of oestrogen receptor, progesterone receptor, Her-2/neu and cancer stage. Moreover, in patients receiving neoadjuvant chemotherapy, those with higher GCIP scores showed potentially more reduction of tumour size compared with those with lower GCIP scores (borderline significance, P = 0.053). CONCLUSIONS: The current data provide evidence that decreased expression of GCIP in vivo is present in human breast carcinoma and indicate that GCIP is a potential indicator of good prognosis. In patients receiving neoadjuvant chemotherapy, it may also have predictive value for the chemotherapeutic response.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Fatores de Transcrição/metabolismo , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Diferenciação Celular , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Resultado do Tratamento
5.
Oncogene ; 27(3): 332-8, 2008 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-17621266

RESUMO

The ribosomal acidic P0 protein, an essential component of the eukaryotic ribosomal stalk, was found to interact with the helix-loop-helix protein human Grap2 and cyclin D interacting protein (GCIP)/D-type cyclin-interacting protein 1/human homolog of MAID protein. Using in vivo and in vitro binding assays, we show that P0 can interact with the N and C termini of GCIP via its N-terminal 39-114 amino-acid residues. Although the P0-GCIP complex was detected mainly in cytoplasmic fraction, polysome profile analysis indicated that the P0-GCIP complex did not coelute with either polysomes or 60S ribosomes, suggesting that GCIP associates with the free form of P0 in the cytoplasm. Transfection of GCIP into MCF-7 cells resulted in decreased levels of pRb phosphorylation. Cotransfection of P0 with GCIP, however, resulted in GCIP-mediated reduction of pRb phosphorylation level which was repressed by P0. Furthermore, overexpression of P0 in breast cancer and hepatocellular cancer cell lines promoted cell growth and colony formation compared to control transfectants. Overexpression of P0 also increased cyclin D1 expression and phosphorylation of pRb at Ser780. Interestingly, P0 mRNA was overexpressed in 12 of 20 pairs of breast cancer/ normal breast specimens (60%). Together, these data indicate that P0 overexpression may cause tumorigenesis in breast and liver tissues at least in part by inhibiting GCIP-mediated tumor suppression.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/metabolismo , Hepatócitos/patologia , Proteínas Ribossômicas/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias da Mama/metabolismo , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Hepatócitos/metabolismo , Humanos , Fosforilação , Domínios e Motivos de Interação entre Proteínas , Mapeamento de Interação de Proteínas , Regulação para Cima
6.
Cytopathology ; 15(2): 104-8, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15056171

RESUMO

The aim of the study was to improve the pre-operative diagnosis of mammary mucinous lesions. All mucinous lesions detected by fine needle aspiration (FNA) and confirmed by histological examination were reviewed by cytological findings, mammographic appearances and sonographic findings. Twenty aspirates had corresponding pathology, including 12 mucinous carcinomas, two mucocele-like lesions (MLL) with atypical ductal hyperplasia, three MLL with ductal hyperplasia and three simple MLL. Simple MLL and mucocele-like with ductal hyperplasia showed scant cellularity, no or rare intact single tumour cells, monolayered arrangement and absence of nuclear atypia. In contrast, most mucinous carcinomas showed higher cellularity, more single tumour cells, three-dimensional clusters, and mild to marked nuclear atypia. However, MLL with atypical ductal hyperplasia showed cytological features overlapping with mucinous carcinoma. MLL had a non-specific mammographic appearance and showed a cystic lesion on sonography. Mucinous carcinoma appeared as a solid mass on sonography and as a distinct nodule on mammography. Based on the combination of FNA cytology and image findings, benign MLL can be correctly distinguished from mucinous carcinoma before surgery.


Assuntos
Adenocarcinoma Mucinoso/patologia , Neoplasias da Mama/patologia , Mama/patologia , Mucocele/patologia , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adulto , Idoso , Biópsia por Agulha Fina , Neoplasias da Mama/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Doença da Mama Fibrocística/diagnóstico por imagem , Doença da Mama Fibrocística/patologia , Humanos , Hiperplasia/patologia , Pessoa de Meia-Idade , Mucocele/diagnóstico por imagem , Radiografia , Sensibilidade e Especificidade , Ultrassonografia
8.
Proteins ; 43(4): 499-508, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11340665

RESUMO

Rhodostomin (Rho) is a snake venom protein isolated from Calloselasma rhodostoma. Rho is a disintegrin that inhibits platelet aggregation by blocking the binding of fibrinogen to the integrin alpha(IIb)beta3 of platelets. Rho produced in Escherichia coli inhibited platelet aggregation with a K(I) value of 263 nM. Although functional, Rho produced in E. coli is misfolded based on our 2D and 3D NMR studies. In order to correct the folding problem, Rho was expressed in Pichia pastoris. The recombinant Rho expressed in P. pastoris inhibited platelet aggregation with a resulting K(I) value of 70 nM. This is the same potency as that of native Rho. CD analysis showed that the secondary structures of Rho are pH-independent and contain 3.5-7.9% alpha-helix, 48.2-50.5% beta-structures, and 42.3-47% coil. The sequential assignment and structure analysis of Rho were obtained using 2D and 3D 15N-edited NMR spectra. These results provide the first direct evidence that highly disulfide-bonded disintegrin can be expressed in P. pastoris with the correct fold. This evidence may serve as the basis for exploring the structure and function relationships as well as the dynamics of disintegrin and its variants.


Assuntos
Dicroísmo Circular , Dissulfetos/química , Escherichia coli/genética , Espectroscopia de Ressonância Magnética , Peptídeos/química , Peptídeos/metabolismo , Pichia/metabolismo , Proteínas Recombinantes de Fusão/isolamento & purificação , Sequência de Aminoácidos , Animais , Escherichia coli/metabolismo , Expressão Gênica , Peptídeos/genética , Pichia/genética , Agregação Plaquetária/efeitos dos fármacos , Reação em Cadeia da Polimerase , Dobramento de Proteína , Estrutura Secundária de Proteína , Proteínas Recombinantes de Fusão/genética , Homologia de Sequência de Aminoácidos , Solubilidade
9.
Chemosphere ; 43(8): 1133-9, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11368230

RESUMO

The predictive accuracy of using the one-dimensional advection-dispersion equation to evaluate the fate and transport of solute in a soil column is usually dependent on the proper determination of chemical retardation factors. Typically, the distribution coefficient (Kd) obtained by fitting the linear sorption isotherm has been extensively used to consider general geochemical reactions on solute transport in a low-concentration range. However, the linear distribution coefficient cannot be adequately utilized to describe the solute fate at a higher concentration level. This study employed the nonlinear equilibrium-controlled sorption parameters to determine the retardation factor used in column leaching experiments. Copper and cadmium transportation in a lateritic silty-clay soil column was examined. Through the explicit finite-difference calculations with a third-order total-variation-diminishing (TVD) numerical solution scheme, all results of the theoretical copper and cadmium breakthrough curves (BTCs) simulated by using the Freundlich nonlinear retardation factors revealed good agreement with the experimental observations.


Assuntos
Cádmio/química , Cobre/química , Modelos Teóricos , Poluentes do Solo/análise , Adsorção , Fenômenos Químicos , Físico-Química , Temperatura
10.
Acta Cytol ; 43(2): 273-6, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10097724

RESUMO

BACKGROUND: Cystic hypersecretory duct carcinoma (CHC) of the breast, first described in 1984, is a rare variant of duct carcinoma. Histologically it is characterized by the formation of dilated ducts and cysts containing an eosinophilic secretory product resembling thyroid colloid. The lining epithelium of the cysts atypically proliferates to form intraductal carcinoma. Only four cases of invasive cystic hypersecretory carcinoma have been reported. CASE: We present a case of invasive CHC with tumor emboli in many lymphatic spaces and axillary nodal metastases. The lesion was also evaluated by fine needle aspiration. Direct smears with Papanicolaou stain were highly cellular and had abundant, intensely staining, orange-to-gray-green thyroid colloid-like material. Epithelial cells, showing a variety of cellular patterns, were indistinguishable from usual ductal carcinoma cells. These cytologic findings may be characteristic enough to suggest cystic hypersecretory carcinoma. CONCLUSION: The cytologic features of CHC are distinctive and correlate with histology. This was the first presentation of colloidlike secretory material in cytologic material with Papanicolaou stain in such a case. Invasive CHC tends to have aggressive behavior. Cystic hypersecretory hyperplasia coexisted in this case.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Adulto , Biópsia por Agulha , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/metabolismo , Coloides/metabolismo , Eosinófilos/patologia , Feminino , Humanos , Metástase Linfática/diagnóstico , Metástase Linfática/patologia
12.
Histopathology ; 34(2): 106-12, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10064388

RESUMO

AIM: BRCA1, a nuclear phosphoprotein, normally functions as a negative regulator of the cell cycle and may be an active inhibitor of neoplastic progression. Mutation of the BRCA1 gene has been demonstrated in 80% of familial breast cancer. Decreased mRNA levels or aberrant subcellular locations of BRCA1 have been identified in breast cancer lines and in sporadic cases of breast cancer tissues. The expression of BRCA1 in large series of variously differentiated breast carcinomas with correlation with other biological parameters has not been clarified. METHODS AND RESULTS: The BRCA1 expression in normal breast tissue (n = 15) and in sporadic cases of invasive ductal carcinoma (n=108) was determined using immunohistochemistry. BRCA1 expression was correlated with other prognostic parameters including p53, c-erbB-2, bcl-2, oestrogen receptor (ER), histological grade, tumour size, axillary lymph node status and age. BRCA1 was exclusively (100%) localized in the nuclei of normal ductal and lobular epithelia. However, this nuclear expression pattern was variable in breast carcinoma (76.8%). Loss of nuclear BRCA1 expression (22 of 108 cases, 20.4%) correlated well with high histological grade (P<0.025) and bcl-2-negative tumours (P<0.05) and frequently in ER-negative tumours. CONCLUSION: BRCA1 nuclear expression could be considered to represent the normal or physiological phenotype. Complete loss of BRCA1 nuclear expression in breast cancer and its correlation with other poor prognostic markers suggest that BRCA1 expression may play an important role in the pathogenesis and prognosis of sporadic breast carcinoma. Altered BRCA1 phenotype may therefore provide an additional prognostic parameter for breast cancer.


Assuntos
Proteína BRCA1/metabolismo , Neoplasias da Mama/metabolismo , Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo
13.
Br J Plast Surg ; 52(5): 365-72, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10618979

RESUMO

Unilateral breast reconstruction with an extended latissimus dorsi musculocutaneous flap was carried out for 12 women in the National Cheng Kung University Hospital. Eleven patients acquired a good or fair result cosmetically. We analysed the net weight of the flap as well as various anthropometric data to see what effect they have on the final aesthetic outcome. The weight of the flap ranged from 180 to 610 g, and the resected specimen weighed from 160 to 635 g. The flap weight was equivalent to 61%-113% of the specimen weight. A satisfactory result could be achieved when the bulk of the flap attained 70% of the mass resected. We also observed that the aesthetic quality is better when the breast is less ptotic. All of the muscle transfers survived completely without any flap loss. The only complications included one minor wound edge slough and another modest seroma formation at the donor site. This reconstructive method is a viable option for young women with small or medium-sized breasts who anticipate pregnancy in the future. It is especially advisable in Oriental society, since the breast size of the patients is generally smaller and the donor scar is hidden, given the hypertrophic tendency of the lower abdominal scar in Asian people undergoing TRAM flap reconstruction.


Assuntos
Povo Asiático , Mamoplastia/métodos , Retalhos Cirúrgicos , Adulto , Idoso , Antropometria , Estética , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/transplante , Transplante de Pele/métodos , Retalhos Cirúrgicos/patologia , Resultado do Tratamento
14.
Acta Cytol ; 42(2): 391-5, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9568143

RESUMO

BACKGROUND: Liposarcoma arising within a phyllodes tumor is extremely rare. To the best of our knowledge, a malignant phyllodes tumor with liposarcomatous stroma diagnosed by fine needle aspiration (FNA) has not been reported before. CASE: A 39-year-old female had a malignant phyllodes tumor with liposarcomatous stroma diagnosed by FNA cytology. Two subtypes of liposarcomatous stroma, including lipomalike differentiated and myxoid, were found in the aspirates. The cytologic findings were very representative of the histologic features. CONCLUSION: It is very important to recognize the cytologic features of such rare tumors. An accurate diagnosis preoperatively by FNA permits better therapy planning.


Assuntos
Neoplasias da Mama/patologia , Lipossarcoma/patologia , Tumor Filoide/patologia , Adulto , Biópsia por Agulha , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Lipossarcoma/diagnóstico , Lipossarcoma/cirurgia , Tumor Filoide/diagnóstico , Tumor Filoide/cirurgia
15.
Hepatogastroenterology ; 44(16): 1037-45, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9261596

RESUMO

BACKGROUND/AIMS: Gastrointestinal obstructions caused by bezoars are uncommon but are encountered with increasing frequency in general surgery. METHODOLOGY: We made a retrospective review of 30 cases treated in the National Cheng Kung University hospital between July 1988 and December 1994. RESULTS: Fourteen patients had either prior gastric surgery (9) or peptic ulcer disease (5) and were categorized as group I. The remaining 16 patients without above conditions were categorized as group II; and seven of them had history of ingestion of Pho Pu Zi (Cordia dichotoma Frost. f.), three had food bolus ingestion, two had diverticulum, two had adhesion and the remaining two had no significant features. Two patients, who received endoscopic removal of gastric bezoar and subsequently developed bowel obstruction, needed operation. Sixteen of 30 who underwent operation within 24 hours after arrival, recuperated uneventfully and most were discharged within a week. Eleven patients who received operation after 24 hours resulted in prolonged hospitalization in 9 and death in two. Re-operation was performed in one case for the recurrence of obstruction by the residual bezoar. CONCLUSION: Dietary factors (Pho Pu Zi or bolus ingestion), and gastrointestinal (GI) anatomical lesion (diverticulum or adhesion) are the profound etiologies for formation of bezoars in cases without previous gastric surgery. On the other hand, gastric factors (previous ulcer surgery or peptic ulcer) play a major role even after ingestion of nonspecific high fiber diet. Early diagnosis, surgical intervention without delay and thorough exploration of the entire GI tract are essential for good postoperative results.


Assuntos
Bezoares/complicações , Sistema Biliar , Colestase/etiologia , Obstrução Intestinal/etiologia , Intestinos , Estômago , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bezoares/diagnóstico , Bezoares/cirurgia , Criança , Colestase/diagnóstico , Colestase/cirurgia , Feminino , Seguimentos , Humanos , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos
16.
J Trauma ; 42(2): 223-30, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9042872

RESUMO

OBJECTIVE: This study used a Wiggers shock model to investigate the effect of the removal of the intestines on the outcome of hemorrhagic shock. METHODS: Rats were subjected to laparotomy for the removal of the entire small and large intestines (experimental group) or a sham operation (control group) before bloodshedding. During the period of shock, animals were maintained at 30-35 mm Hg arterial pressure for 2 hours. After reinfusion of the shed blood, rats were observed for over 3 hours for survival. The average volumes (mean +/- SEM) of shed blood were 6.84 +/- 0.23 mL (experimental group) and 6.49 +/- 0.39 mL (control group), with no significant difference between the two (p > 0.05). RESULTS: This protocol resulted in a 42% mortality (11 of 26) in the control group and 0% mortality (0 of 25) in the experimental group (p < 0.005, chi2). Moreover, in the survivors, the mean arterial pressure was significantly lower in the control (65.7 +/- 4.3 mm Hg) than in the experimental group (78.2 +/- 3.5 mm Hg) at the end of the experiment (p < 0.05). Comparing volume status, neither serial hematocrit values nor body weight changes through the experiment had a significant difference between the two groups (p's > 0.05). Serial quantitation of blood levels of tumor necrosis factor-alpha (TNF-alpha) revealed that systemic TNF-alpha concentrations peaked at 4 hours after shock in both groups. TNF-alpha levels were not reduced by enterectomy. Instead, the peak concentrations were significantly higher in the enterectomized (387.5 +/- 36.5 pg/mL, n = 13) than in the sham-enterectomized group (175.7 +/- 35.9 pg/mL, n = 12,p < 0.001). Limulus assay, used to detect endotoxins in the blood at 2 hours after restoration of blood volume, showed no endotoxemia in any specimen from either group. Four hours after hemorrhagic shock, blood levels of platelet-activating factor, quantitated by the radioimmunoassay method, were 2.88 +/- 0.18 ng/mL (experimental group, n = 8) and 2.32 +/- 0.32 ng/mL (control group, n = 6). The difference between these two means was not significant (p > 0.05). Measurement of hepatic adenosine triphosphate (ATP) by the luminometric method showed that hepatic ATP contents were significantly reduced in both groups after shock (p's < 0.05). However, a higher magnitude of hepatic ATP depletion occurred in the control group; significantly lower amounts of ATP in the liver tissues of the sham-enterectomized group (367 +/- 95 nmol/g, n = 7) than in that of the enterectomized group (870 +/- 100 nmol/g, n = 13) were observed at 5 hours after shock (p < 0.05). CONCLUSIONS: These experimental findings show that, in the absence of the intestines, hemorrhagic shock is associated with both an improved outcome and higher hepatic ATP levels in rats, suggesting the importance of intestinal participation in the process leading to hepatic ATP depletion as well as irreversibility in shock.


Assuntos
Intestinos/fisiologia , Choque Hemorrágico/fisiopatologia , Trifosfato de Adenosina/análise , Animais , Modelos Animais de Doenças , Endotoxinas/sangue , Fígado/química , Masculino , Fator de Ativação de Plaquetas/análise , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/mortalidade , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/análise
17.
HPB Surg ; 10(5): 305-10, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9298385

RESUMO

Although the operative mortality of pancreaticoduodenal resection has decreased recently, the operative morbidity resulting from a leaking pancreatic anastomosis remains high. We described our experience in 50 consecutive cases with a simple, secure end to side pancreaticojejunostomy. We used a paediatric nasogastric tube in the pancreatic remnant duct as a temporary external pancreatic drain. There were 29 men and 21 women ranging from 12 to 84 years with a median age of 61 years. Forty-two patients underwent a standard Whipple procedure and eight a pylorus preserving pancreaticoduodenectomy. Average operating time was 270 minutes with a range of 170 to 480 minutes. The pancreaticojejunostomy could be constructed in a mean of 8 minutes. Intraoperative blood loss ranged from 150 to 3500 mL with a mean of 910 mL. Twenty-five patients (50%) received no blood transfusion. The consistency of the pancreatic remnant was hard in 12 patients (24%) and normal in 38 patients (76%). The pancreatic duct was dilated (> 4 mm) in 15 patients (30%). There was no operative mortality and only three (6.0%) minor leaks from the pancreatic anastomosis which healed spontaneously. It was difficult to determine if the leaks were related to the consistency of the pancreatic remnant, the size of the pancreatic duct, the amount of intraoperative blood loss, operating time, sex of the patient or experience of the surgeon, as there were only three leaks. We concluded that our technique for pancreaticojejunal anastomosis following pancreaticoduodenectomy was safe and applicable to, standard Whipple or pylorus preserving pancreaticoduodenectomy, small or dilated pancreatic ducts, normal or fibrotic pancreas.


Assuntos
Pancreaticoduodenectomia , Pancreaticojejunostomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias
18.
Immunol Invest ; 25(5-6): 495-505, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8915686

RESUMO

The membrane IgE peptide (MEP) encompassing 20 amino acids proximal to the C terminus of membrane IgE molecules, and secretory IgE peptides (SEP), spanning CH epsilon 1 to 4 domain were synthesized according to IgE genomic and cDNA sequences. Inhibition of anti-KLH and anti-BGG IgE, but not IgG responses was observed in mice treated with MEP-protein but not SEP-protein conjugates in complete/incomplete Freund's adjuvant. Only IgE responses directed toward proteins to which MEP was conjugated, were inhibited, while IgE responses to a concomitantly injected, unrelated antigen were not. Inhibition of antigen-specific IgE was also not correlated with levels of anti-MEP or anti-IgE antibodies, moreover, levels of total IgE remained comparable among mice treated with MEP-protein conjugates, native or glutaraldehyde-modified protein carriers. This observation may have significant import on future design of IgE immunotherapy. Treatment of MEP conjugated allergens prevents formation of IgE-anti-IgE complexes because the MEP sequence is absent from the secretory IgE.


Assuntos
Antígenos/farmacologia , Epitopos/imunologia , Tolerância Imunológica , Imunoglobulina E/biossíntese , Peptídeos/imunologia , Receptores de Antígenos de Linfócitos B/metabolismo , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Antígenos/metabolismo , Proteínas de Transporte/imunologia , Proteínas de Transporte/farmacologia , Feminino , Adjuvante de Freund/administração & dosagem , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Ovalbumina/imunologia , Ovalbumina/metabolismo , Ovalbumina/farmacologia , Peptídeos/administração & dosagem , Peptídeos/metabolismo , Receptores de Antígenos de Linfócitos B/administração & dosagem
19.
Mol Immunol ; 33(2): 179-87, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8649439

RESUMO

Membrane-bound immunoglobulins, mIgs, are displayed as transmembrane proteins on the surface of B cells, where they serve as antigen receptors. The mIgs are anchored to the membrane through a carboxy-terminal extension of the immunoglobulin heavy chain. Three distinct structural regions of these membrane-anchor peptides, of mouse and human mIgs, have been delineated: (1) a central conserved stretch of 25 hydrophobic, unchanged amino acid residues, which spans the membrane lipid bilayer; (2) a C-terminal hydrophilic region of 3-28 amino acids, which is intracytoplasmic; and (3) an N-terminal extracellular hydrophilic region of 13-67 amino acids, which is isotype-specific. Here we report predicted secondary and tertiary structures of the third structural region of the membrane anchoring peptide along with corroborating experimental evidence. The predictions of secondary and tertiary structure indicate that most of these regions can assume an chi-helical conformation. Circular dichroism spectroscopy of corresponding synthetic peptide confirms this essential feature. The choice of solvent and pH have dramatic effects on peptide helicity; solvent conditions consistent with a membrane-proximal environment promote helicity. Additional studies suggest that the two adjacent extracellular peptides may be stabilized through coiled-coil interactions similar to those described for some other transmembrane proteins.


Assuntos
Receptores de Antígenos de Linfócitos B/química , Sequência de Aminoácidos , Animais , Dicroísmo Circular , Espaço Extracelular/imunologia , Humanos , Isotipos de Imunoglobulinas/química , Isotipos de Imunoglobulinas/genética , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Molecular , Peptídeos/química , Peptídeos/genética , Peptídeos/imunologia , Estrutura Secundária de Proteína , Receptores de Antígenos de Linfócitos B/genética , Homologia de Sequência de Aminoácidos
20.
Biotechnology (N Y) ; 13(8): 779-86, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9634808

RESUMO

Human hybridoma cell lines secreting IgG specific for the major allergen in the pollen of short ragweed, Amb a I, were established from patients who had been receiving antigen injections for immunotherapy. Recombinant Ig genes were then constructed by cloning the heavy and light chain variable region genes of the human hybridoma cell line and joining them to the human alpha or kappa constant region genes in mammalian expression vectors. Amb a I-specific IgA was expressed in two mouse myeloma cell lines, NS0 and Sp2/0. In both systems, transfected alpha and kappa chains were assembled into IgA monomers or into dimers covalently linked by the endogenous murine J chains. We propose that recombinant IgA monoclonal antibodies specific for airborne allergens may be applied to the mucosal surface of the nasal linings or of the lower airway of sensitized individuals to inhibit the entry of allergenic molecules across the mucosal epithelium and, therefore, to prevent the development of allergic responses.


Assuntos
Alérgenos/imunologia , Antígenos/uso terapêutico , Imunoglobulina A/imunologia , Imunoterapia , Pólen/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais , Especificidade de Anticorpos , Sequência de Bases , Linhagem Celular , Estudos de Viabilidade , Humanos , Hipersensibilidade/terapia , Camundongos , Dados de Sequência Molecular , Ligação Proteica , Proteínas Recombinantes/isolamento & purificação
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