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Biomedical subjects

Atsushi Watanabe

Publications and source records attributed to Atsushi Watanabe.

At least 37 records · Page 2Linked to original sources

Systematic node dissection by VATS is not inferior to that through an open thoracotomy: a comparative clinicopathologic retrospective study.

BACKGROUND: Major pulmonary resection with systematic node dissection (SND) for early lung cancer by video-assisted thoracic surgery (VATS) is performed in many institutes, but the feasibility of SND for early lung cancer by VATS remains controversial. The aim of this study was to elucidate the feasibility and safety of SND by VATS. METHODS: Three hundred fifty patients with clinical stage I lung cancer who underwent pulmonary major resection with SND between 1998 and 2003 were enrolled in this study. Of these patients, 191 (VATS group) underwent pulmonary resection with SND by VATS; 159 patients (open thoracotomy [OT] group) did so through anterolateral thoracotomy. The clinical and pathologic data, including the number of dissected nodes in each nodal station, of the 2 groups were compared to evaluate the feasibility of SND by VATS. RESULTS: Pathologic data showed that, in the VATS group, more patients had adenocarcinoma (P = .0078) and fewer patients had advanced factors than the OT group. The greatest tumor diameter was 24.5 mm and 29.6 mm in the VATS group and OT group, respectively (P < .0001). The total number of mediastinal nodes dissected in right upper lobectomy plus right middle lobectomy (RUL+RML), right lower lobectomy (RLL), left upper lobectomy (LUL), and lower left lobectomy (LLL) also did not differ between the 2 groups. The total number of mediastinal nodes dissected in RUL+RML, RLL, LUL, and LLL was 19.7 in the VATS group versus 22.0 in the OT group (P = .122), 23.4 versus 21.0 (P = .241), 14.8 versus 17.5 (P = .123), and 18.8 versus 15.8 (P = .202), respectively. The number of dissected nodes in each nodal station in RUL+RML, RLL, LUL, and LLL was similar between the 2 groups. Operative mortality, morbidity, or recurrence did not differ between the 2 groups. CONCLUSIONS: With regard to the number of dissected nodes, SND by VATS was not inferior to that of OT. SND by VATS is technically feasible and safe, and seems acceptable for clinical stage I lung cancer.

Disease-Free Survival↗

Visualization of newly deposited tau in neurofibrillary tangles and neuropil threads.

Neurofibrillary tangles (NFTs) and neuropil threads (NTs), the major hallmark of Alzheimer disease (AD), are composed of the microtubule-associated protein tau that has undergone posttranslational modifications, including deamidation and isomerization on asparaginyl or aspartyl residues. Because such modifications represent protein aging, we generated 2 antibodies, TM4, specific for Asp-387 of tau, and iD387, specific for isoAsp-387 of tau, to investigate the evolution of NFTs and NTs. On Western blots of Sarkosyl-insoluble fractions, TM4 strongly labeled paired helical filament-tau (PHF-tau), whereas iD387 preferentially labeled PHF smear. Thus, it is reasonable to postulate that TM4-labeled tau (unmodified tau species) represents more recent deposition, and iD387-labeled tau (modified tau species) represents earlier deposition. Unexpectedly, TM4 immunostained even highly evolved NFTs, suggesting that deposition of newly produced tau continues until neuronal death. iD387 labeled the whole profile of NFTs up to distal dendritic branches, whereas TM4 staining was localized to particular portions of NFTs in proximal dendrites and neuronal perikarya. In NTs, TM4 preferentially labeled the outer portion, whereas iD387 intensely labeled the core portion. Based on TM4-positive NFT counts and total NFT counts, we speculate that NFTs in the human hippocampus are produced at a constant rate irrespective of the disease stage.

Alzheimer Disease↗

Expression of cochlin in the vestibular organ of rats.

The COCH gene mutated in autosomal dominant sensorineural deafness (DFNA9) encodes cochlin, a major constituent of the inner ear extracellular matrix. Cochlin constitutes 70% of the inner ear protein and cochlin isoforms can be classified into three subgroups, p63s, p44s and p40s. Symptoms of some DFNA9 patients are consistent with those of Ménière's disease. Here, we report the expression of cochlin in the vestibular organ of rats using isoform-specific antibodies that recognize all three isoforms. Cochlin is highly expressed in the stromata of the maculae of otolithic organs and cristae of semicircular canals, and in the channels in the bony labyrinth that transmit the dendritic innervation to the cristae and maculae. Cochlin cannot be detected in the sensory cells, dark cells, nor in the acellular structures, otolithic membrane or in the cupula. These findings support the theory that deposition of acidophilic substance in the inner ear caused by mutation of cochlin can induce a secondary retrograde dendritic degeneration of the vestibular nerves.

Animals↗

[Lung cancer in patients with idiopathic interstitial pneumonia].

The purpose of this study was to determine the outcome of surgical treatment for lung cancer concomitant with idiopathic interstitial pneumonia (IIP). Between 1994 and 2003, 673 patients with primary lung cancer were treated. Forty-four patients (6.54%) of 673 patients were complicated with IIP. Their data were retrospectively reviewed. There were 37 male and 7 female with an average age of 67 years. They underwent 7 wedge resections of the lung, 3 segmentectomies, 32 lobectomies and 2 bi-lobectomies as surgical treatment for lung cancer. Five of these 44 patients died of acute exacerbation of IIP after the operation. The exacerbation occurred in an average postoperative day of 5 (range, 3 to 7) day. Preoperative values of serum CRP, LDH, SP-D and KL-6 failed to predict the occurrence of the exacerbation of IIP after the surgery. The preoperative value of %DLCO was lower in patients with the exacerbation than patients without the exacerbation (42.3+/-9.6% versus 66.8+/-18.8%, p=0.018). The postoperative 5-year survival rate for pathological stage I lung cancer were 84.9% and 70.2% (p=0.134) for patients without IIP and patients with IIP, respectively. Although the acute exacerbation of IIP after the surgery caused catastrophic outcomes, the long-term results in surgical treatment for stage I lung cancer simultaneously concomitant with IIP were not so poor. It is very important to avoid the postoperative exacerbation and further effort and research are required to avoid the exacerbation.

Aged↗

Node dissection for solitary interlobar node metastasis from renal cell carcinoma by VATS.

We present an unusual case of a patient with a right pulmonary interlobar node metastasis from renal cell carcinoma following nephrectomy. She underwent interlobar node dissection (ND) by video-assisted thoracoscopic surgery (VATS). Interlobar ND without lobectomy by VATS has not been reported until now in English literature. The retraction of the right intermediate bronchus is a useful technique during this procedure.

Carcinoma, Renal Cell↗

Pulmonary sequestration associated with asymptomatic aspergillosis.

Intralobar pulmonary sequestration associated with asymptomatic aspergillosis is a rare case. We describe the case of a 65-year-old woman with intrapulmonary sequestration, anomalous systemic arterial supply to the left lower lobe and aspergillosis who underwent left lower lobectomy and ligation of an anomalous artery by Video-Assisted Thoracoscopic surgery (VATS). Pathological examination showed the parenchymal distortion and chronic inflammation. Aspergillus were found in the cyst. VATS lobectomy for intralobar pulmonary sequestration is a safe and valid procedure.

Aged↗

Adipogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice-including relationship of sex differences.

We have previously demonstrated that adipose-derived stromal cells (ASCs) as well as bone marrow-derived stromal cells (BSCs) differentiate into a variety of cell lineages both in vitro and in vivo. Both types are considered to include mesenchymal stem cells. Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have also previously reported the plasticity of BSCs and ASCs. In this study, we focused on adipogenic differentiation in vitro by ASCs harvested from GFP transgenic mice. Moreover, preadipocytes and mature adipocytes were harvested at the same time, and the cells were cultured to compare them with ASCs. Inguinal fat pads from GFP transgenic mice were used for the isolation of ASCs, preadipocytes, and mature adipocytes. After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks. Adipogenic differentiation of ASCs was assessed by Oil Red O staining and the expression of the adipocyte specific peroxisome proliferative activated receptor gamma2 (PPAR-gamma2) gene. These ASCs stained positively, and expression of PPAR-gamma2 was detected. Moreover, we also tried to characterize the influence of sex differences on the adipogenic differentiation of ASCs harvested from both male and female mice. This was assessed by the expression levels of the PPAR-gamma2 gene using real-time PCR. The results showed that the expression levels of ASCs harvested from female mice were a maximum of 2.89 times greater than those harvested from male mice. This suggests that the adipogenic differentiation of ASCs is closely related to sex differences.

Adipose Tissue↗

Identification of a novel Cochlin isoform in the perilymph: insights to Cochlin function and the pathogenesis of DFNA9.

The COCH gene mutated in DFNA9, an autosomal dominant hereditary sensorineural hearing loss and vestibular disorder, encodes Cochlin. Previously, we reported three bovine Cochlin isoforms, p63s, p44s, and p40s, which exhibit significant molecular heterogeneity in vivo. Here we have characterized Cochlin isoforms by generating four isoform-specific anti-Cochlin antibodies. The same three Cochlin isoforms, p63s, p44s, and p40s, were detected in human and cow inner ear tissue; however, p44s and p40s were not detected in perilymph. We identified a novel short 16kDa isoform in human perilymph and a 18-23kDa isoform in cow perilymph, named Cochlin-tomoprotein (CTP), corresponding to the N-terminus of full-length Cochlin (p63s) and the LCCL domain. Notably, CTP contains all of the known mutation sites associated with DFNA9. The pathogenesis of DFNA9 is not fully clarified as yet, and this novel perilymph-associated CTP isoform might provide mechanistic clues to how mutations in the COCH gene damage the inner ear function.

Amino Acid Sequence↗

Osteogenic and chondrogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice.

Recent studies suggest that human adipose tissue contains pluripotent stem cells similar to bone marrow-derived stem cells. Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have previously demonstrated that bone marrow-derived stromal cells (BSCs) differentiate into a variety of cell lineages both in vitro and in vivo. In the present study, we extend this approach to characterize adipose tissue-derived stromal cells, sometimes called processed lipoaspirate (PLA) cells. Adipose-derived stromal cells (ASCs) were isolated from inguinal fat pads of GFP transgenic mice after extensive washing with phosphate-buffered saline and treatment with collagenase. After primary culture in a control medium (Dulbecco's modified Eagle's medium+10% fetal bovine serum) and expansion to two passages, the cells were incubated in either an osteogenic medium (Dulbecco's modified Eagle's medium+10% fetal bovine serum+dexamethasone+ascorbate-2-phosphate+beta-glycerophosphate) or a chondrogenic medium (Dulbecco's modified Eagle's medium+1% fetal bovine serum+insulin+ascorbate-2-phosphate+transforming growth factor-beta1) for 2-4 weeks to induce osteogenesis and chondrogenesis, respectively. Osteogenic differentiation was assessed by von Kossa and alkaline phosphatase staining, while chondrogenic differentiation was assessed by Alcian blue staining. Expression of osteocyte specific osteopontin, osteocalcin, and alkaline phosphatase, and chondrocyte specific aggrecan and type II/X collagen was confirmed by RT-PCR. ASCs incubated in the osteogenic medium were stained positively for von Kossa and alkaline phosphatase staining. Expression of osteocyte specific genes, except osteocalcin, was also detected. Incubation with chondrogenic medium induced Alcian blue positive cells and expression of aggrecan and type II/X collagen genes. No osteochondrogenic differentiation was observed in cells incubated in the control medium. ASCs from GFP transgenic mice have both osteogenic and chondrogenic potential in vitro. Since this cell population can be easily identified through fluorescence microscopy, it may be an ideal source of ASCs for further experiments on stem cell biology and tissue engineering.

Adipose Tissue↗

Extrapleural thoracoscopic excision of a mediastinal bronchogenic cyst in a patient with dense pleural adhesions.

We report the case of a 70-year-old man with dense pleural adhesions who underwent an excision of a mediastinal bronchogenic cyst by video-assisted thoracoscopic surgery (VATS) through an extrapleural approach. The VATS approach for the diagnostic and therapeutic excision of a mediastinal tumor is easier and safer than an intrapleural approach if a patient has dense pleural adhesions.

Aged↗

Avoiding chest tube placement after video-assisted thoracoscopic wedge resection of the lung.

OBJECTIVE: A chest tube is usually placed in the pleural cavity after wedge resection of the lung, even after thoracoscopic procedures. The aim of this study was to determine the validity and safety of postoperative management without chest tube placement for patients undergoing thoracoscopic wedge resection of the lung. METHODS: Between 1998 and 2002, 93 patients underwent thoracoscopic wedge resection of the lung. In January 2000, we established the following criteria for avoiding chest tube placement: (1) absence of air leaks during intraoperative alternative sealing test, (2) absence of bullous or emphysematous changes on inspection, (3) absence of severe pleural adhesions, and (4) absence of prolonged pleural effusion requiring chest drainage preoperatively. Seventeen of 93 patients did not satisfy the criteria. The other 76 patients were divided into two groups: group 1 consisted of 34 patients who underwent thoracoscopic resection before 1999 and in whom a chest tube was routinely placed in spite of retrospectively meeting the criteria, group 2 consisted of 42 patients who underwent thoracoscopic resection after 2000 and in whom chest tube was not placed. The clinical data were evaluated and analyzed between the two groups. RESULTS: Two patients in group 1 required new intervention after removal of a chest tube that had been inserted during the operation due to recurrence of a pneumothorax, so did two patients in group 2 after the operation. The rate of late pneumothorax requiring intervention is similar in groups 1 and 2. No differences were found between the two groups with regard to postoperative chest pain and hospital stay. No patients experienced a significant adverse outcome. CONCLUSIONS: Avoiding the chest tube placement did not increase postoperative morbidity if carefully selected criteria are met.

Adolescent↗

Surgical experience with resection en bloc of intramedullary astrocytomas and ependymomas in the cervical and cervicothoracic region.

We performed 8 operations on 7 patients with benign intramedullary astrocytomas and ependymomas in the cervical and cervicothoracic region. All patients initially underwent gross total tumor resection en bloc. One patient with an astrocytoma showed tumor recurrence postoperatively, and underwent a second operation resulting in subtotal removal. The follow-up after the initial surgery ranged from 2.7 to 19.7 years (mean 8.5 years). Symptomatic improvement was observed in 6 patients after the initial operation. Two patients showed postoperative neurological deterioration, one with an ependymoma and the other after the second operation. No operative complications or deaths, nor postoperative respiratory dysfunction occurred. Benign intramedullary astrocytomas and ependymomas of the cervical and cervicothoracic spinal cord can be treated by radical resection en bloc with a low morbidity and recurrence, as well as acceptable outcomes. We describe here the surgical technique for en bloc tumor removal.

Adolescent↗

Prognostic factors for myasthenic crisis after transsternal thymectomy in patients with myasthenia gravis.

OBJECTIVE: The purpose of this study was to assess which clinical features of patients with myasthenia gravis predict postoperative respiratory problems due to myasthenic crisis after transsternal thymectomy. METHODS: One hundred twenty-two patients who underwent transsternal thymectomy in our institute were analyzed retrospectively. Fourteen of those experienced myasthenic crisis and required prolonged (48 hours or more) postoperative mechanical ventilation. The following factors were evaluated: sex, age, body mass index, grade of symptom, disease interval, existence of thymoma, history of preoperative crisis, doses of anticholinesterase drugs, steroid use, pulmonary function, serum anti-acetylcholine receptor antibody, history of pulmonary disease, presence of other disease, operation time, and blood loss. RESULTS: Univariate analysis revealed preoperative bulbar symptoms (odds ratio = 14.246, P =.001), history of preoperative myasthenic crisis (7.091,.018), and preoperative serum level of anti-acetylcholine receptor antibody > 100 nmol/L (4.098,.044) were prognostic factors for postoperative myasthenic crisis. On the other hand, multivariate logistic regression analysis revealed preoperative bulbar symptoms (33.333,.004), preoperative serum level of anti-acetylcholine receptor antibody > 100 nmol/L (7.874,.020), and intraoperative blood loss > 1000 mL (18.519,.048) were prognostic factors for postoperative myasthenic crisis. CONCLUSIONS: In this study, postoperative myasthenic crisis after transsternal thymectomy in 122 patients with myasthenia gravis was affected by the existence of preoperative bulbar symptoms, history of preoperative myasthenic crisis, preoperative serum level of anti-acetylcholine receptor antibody > 100 nmol/L, and intraoperative blood loss > 1000 mL. Meticulous preoperative and postoperative care should be carried out to prevent postoperative myasthenic crisis in patients with these prognostic factors.

Adolescent↗

The use of a lateral stabilizer increases the incidence of wound trouble following the Nuss procedure.

BACKGROUND: A lateral stabilizer has been used to prevent bar displacement during the Nuss procedure for pectus excavatum repair in pediatric patients. We experienced wound troubles in patients who had a stabilizer placed within them. The aim of this study was to examine the effect of a lateral stabilizer and other clinical factors on wound troubles after the Nuss procedure. METHODS: 53 patients with pectus excavatum underwent repair by the Nuss procedure. Preoperative clinical data, operative data, and postoperative complications were examined in all patients. RESULTS: A lateral stabilizer was placed in 29 of the 53 patients. Short-term results were excellent in 42 patients (79.2%). Postoperative complications involved pneumothorax requiring drainage in two patients, atelectasis in one patient, pleural effusion in three patients, deterioration of scoliosis in one patient, erythema in one patient, persistent pain in two patients, bar displacement in four patients, and local wound complications (Seroma with dermatitis due to pressure damage) in five patients. All seromas with dermatitis due to pressure damage were initially aseptic around lateral stabilizers and became infected in four patients after resection of the seroma or spontaneous perforation. Removal of both the pectus bar and lateral stabilizer was performed in two of those four patients and the lateral stabilizer was removed in the other two patients to prevent catastrophic infection such as empyema or mediastinitis. The use of a lateral stabilizer increases the incidence of wound trouble (p = 0.041). CONCLUSIONS: Although the Nuss procedure has evolved into an effective method for pectus excavatum repair, the use of a lateral stabilizer increases the incidence of wound difficulties.

Adolescent↗

Molecular aging of tau: disulfide-independent aggregation and non-enzymatic degradation in vitro and in vivo.

Smearing from high-molecular-mass regions to low-molecular-mass regions on western blot is the most striking observation of the tau making up paired helical filaments in brain tissues affected by Alzheimer's disease. Because our previous study showed site-specific deamidation/isomerization in the smeared tau in vivo, a feature of protein aging, recombinant tau was subjected to prolonged (up to 90 days) in vitro incubation. Carboxymethylated tau at approximately 50 kDa gradually disappeared and was converted to dimers and to high- and low-molecular-mass smearing. In addition, the same site-specific deamidation/isomerization as previously identified in the smeared tau in vivo emerged. Most importantly, tau was spontaneously degraded, generating fragments that start from bulky residues next to asparaginyl residues. This spontaneous degradation of tau probably represents non-enzymatic cleavage through the formation of succinimide intermediates. Similar degradation products starting from the bulky residues next to asparaginyl residues were found in the smeared tau in vivo partially purified from the homogenates from Alzheimer's disease brains.

Aging↗

Chondrogenic and osteogenic differentiation of adipose-derived stem cells isolated from GFP transgenic mice.

Recent studies suggest that human adipose tissue contain pluripotent cells similar to bone marrow-derived stromal cells (BSCs). Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have previously demonstrated that BSCs differentiate into a variety of cell lineages both in vitro and in vivo). In the present study, we extend this approach to characterize adipose-derived stromal cells (ASCs)). These cells derived from human are sometimes called processed lipoaspirate (PLA) cells. ASCs were prepared from inguinal fat pads of GFP transgenic mice after extensive washing with PBS and treatment with collagenase. After the primary culture in control medium (DMEM + 10% FBS), the cells were incubated in either chondrogenic medium (DMEM + 1% FBS + insulin + ascorbate 2-phosphate + TGF-beta 1) or osteogenic medium (DMEM + 10%FBS + dexamethasone + ascorbate-2-phosphate + beta-glycerophosphate) for two to four weeks. Chondrogenic differentiation was assessed by Alcian blue staining, while osteogenic differentiation was by von Kossa and Alkaline phosphatase staining. ASCs incubated in chondrogenic medium induced Alcian blue positive cells. Incubation with osteogenic medium became positive for von Kossa and Alkaline phosphatase staining. No osteochondrogenic differentiation was observed in cells incubated with control medium. This cell population can be easily identified through fluorescence microscope, it should be an ideal source of ASCs for further experiments of stem cell biology and tissue engineering.

Adipocytes↗

[Two younger male patients with rapidly progressing pulmonary pleomorphic carcinoma].

We report 2 cases of pulmonary pleomorphic carcinoma. The patient in case 1 was a 44-year-old man who was admitted to our hospital complaining of dry cough and dyspnea on exertion. Chest radiography and CT showed a huge tumor with left pleural effusion. Percutaneous biopsy suggested malignancy. As distant metastasis was not found and as cytological examination of pleural effusion gave a result of class II, we attempted to perform left pneumonectomy. However, we performed partial resection of the tumor because it had invaded the aorta, pulmonary artery, pericardium and pleura. The pathological diagnosis was pleomorphic carcinoma, p-T4 N2 M0. After the operation, we performed systemic chemotherapy, including cisplatin and irinotecanm with little effect (PD). The patient died of progression of the tumor. Case 2 was a 34-year-old man who was admitted to our hospital complaining of fever and general malaise. Chest radiography and CT showed a tumor in the left upper lobe. As no distant metastasis was found, we tried left upper lobectomy. However, we performed left upper segmentectomy and lymph node dissection because of invasion of the aorta and the chest wall, and because of hypersegmentation of the left upper lobe. Pathological diagnosis was pleomorphic carcinoma, p-T4 N0 M0. After the operation, the mediastinum was subjected to radiation therapy. However, a metastatic tumor was found in the pelvis after this radiation was given. We performed systemic chemotherapy with substances including cisplatin, gemcitabine and vinorelbine, but with little effect (PD). The patient died of peritonitis and pleuritis due to the recurrence and progression of the tumor. Both cases had rapidly growing neoplasms showing little sensitivity to chemotherapy or radiotherapy. Pulmonary pleomorphic carcinoma is suggested to be type of lung cancer with a poor prognosis when the tumor is not resected in the early stages.

Adenocarcinoma↗