[Progress in diagnosis of and therapy for diabetic polyneuropathies].
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Achilles Tendon↗
Biomedical subjects
Masayuki Baba
Publications and source records attributed to Masayuki Baba.
Upregulation of striatal adenosine A2A receptor mRNA in 6-hydroxydopamine-lesioned rats intermittently treated with L-DOPA.
To determine whether the adenosine A2A receptor might play a role in L-DOPA-induced dyskinesia in Parkinson's disease, we analyzed changes in the expression of A2A receptor mRNA in response to intermittent treatment with L-DOPA in rats with dopaminergic denervation by 6-hydroxydopamine (OHDA) infusion into the medial forebrain bundle. Intermittent treatment with L-DOPA increased A2A receptor mRNA levels in the dopamine-depleted striatum of 6-OHDA-lesioned rats exhibiting behavioral sensitization to L-DOPA. These results suggest that A2A receptor activation is associated with the development of motor complications induced by L-DOPA treatment.
Animals↗
Rapid change of tonotopic maps in the human auditory cortex during pitch discrimination.
OBJECTIVE: To study early cognitive processes and hemispheric differences in the primary auditory cortex during selective attention. METHODS: We measured auditory evoked magnetic fields (AEFs) to 400 and 4000 Hz tone pips that were randomly presented at the right or left ear. Subjects paid attention to target stimuli during pitch (high or low) or laterality (left or right) discrimination tasks. In the control session, 400 or 4000 Hz tone alone was presented at the left or right ear. We calculated the location and strength of N100m dipole for 400 and 4000 Hz tones, based on the AEFs obtained from the hemisphere contralateral to the stimulated ear. RESULTS: N100m amplitude increased in both hemispheres in pitch or laterality discriminating conditions. N100m latency also shortened during selective attention. The N100m dipole distance between 400 and 4000 Hz tones was enlarged, especially in the right auditory cortex during pitch discrimination task, but was unchanged during the laterality discrimination task. CONCLUSIONS: We conclude that these dynamic changes in the N100m dipole reflect short-term plastic changes in the primary auditory cortex, supporting early selection models. SIGNIFICANCE: This work is the first to disclose short-term plastic changes during pitch discrimination in the human auditory cortex based on the analysis of magnetoencephalography.
Acoustic Stimulation↗
Biological features of bronchial squamous dysplasia followed up by autofluorescence bronchoscopy.
Some dysplasias in the bronchial epithelium are thought to be precancerous lesions that can develop into squamous cell carcinomas. In this investigation, we assessed the biological behavior of bronchial squamous dysplasia in order to define which dysplasias have the potential to progress to squamous cell carcinoma. Using autofluorescence bronchoscopy, we followed up periodically localized dysplasias and examined for correlation between histological outcome and smoking status during the follow-up period, telomerase activity, Ki-67 labeling index, and p53 immunoreactivity of initial biopsy specimens. Ninety-nine dysplasias from 50 participants mainly with sputum cytology suspicious or positive for malignancy were followed up. Of 99 dysplasias, 3 dysplasias progressed to squamous cell carcinoma, 41 dysplasias remained as dysplasia, 6 dysplasias changed to metaplasia, 14 dysplasias changed to hyperplasia, and 35 dysplasias regressed to bronchitis or normal bronchial epithelium. There were no significant associations between histological outcome and smoking status. Mean initial telomerase activity and Ki-67 labeling index values in the dysplasias increased in proportion to the severity of the histological outcome at the second biopsy. There was also a significant difference between p53-positive and p53-negative dysplasia in terms of histological outcome at the second biopsy. Our results suggested that dysplasias with high telomerase activity, increased Ki-67 labeling index, and p53-positivity tended to remain as dysplasia and might have the potential to progress to squamous cell carcinoma. Patients with dysplastic lesions with these characteristics should be carefully followed up.
Aged↗
Overview of clinical experiences on carbon ion radiotherapy at NIRS.
BACKGROUND AND PURPOSE: Carbon ion beams provide physical and biological advantages over photons. This study summarizes the experiences of carbon ion radiotherapy at the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences. MATERIALS AND METHODS: Between June 1994 and August 2003, a total of 1601 patients with various types of malignant tumors were enrolled in phase I/II dose-escalation studies and clinical phase II studies. All but malignant glioma patients received carbon ion radiotherapy alone with a fraction number and overall treatment time being fixed for each tumor site, given to one field per day and 3 or 4 days per week. In dose-escalation studies, the total dose was escalated by 5 or 10% increments to ensure a safe patient treatment and to determine appropriate dose levels. RESULTS: In the initial dose-escalation studies, severe late complications of the recto-sigmoid colon and esophagus were observed in those patients who received high dose levels for prostate, uterine cervix and esophageal cancer. Such adverse effects, however, did shortly disappear as a result of determining safe dose levels and because of improvements in the irradiation method. Carbon ion radiotherapy has shown improvement of outcome for tumor entities: (a) locally advanced head and neck tumors, in particular those with non-squamous cell histology including adenocarcinoma, adenoid cystic carcinoma, and malignant melanoma; (b) early stage NSCLC and locally advanced NSCLC; (c) locally advanced bone and soft tissue sarcomas not suited for surgical resection; (d) locally advanced hepatocellular carcinomas; (e) locally advanced prostate carcinomas, in particular for high-risk patients; (f) chordoma and chondrosarcoma of the skull base and cervical spine, and (g) post-operative pelvic recurrence of rectal cancer. Treatment of malignant gliomas, pancreatic, uterine cervix, and esophageal cancer is being investigated within dose-escalation studies. There is a rationale for the use of short-course RT regimen due to the superior dose localization and the unique biological properties of high-LET beams. This has been proven in treatment of NSCLC and hepatoma, where the fraction number has been successfully reduced to 4-12 fractions delivered within 1-3 weeks. Even for other types of tumors including prostate cancer, bone/soft tissue sarcoma and head/neck tumors, it was equally possible to apply the therapy in much shorter treatment times as compared to conventional RT regimen. CONCLUSION: Carbon ion radiotherapy, due to its physical and biologic advantages over photons, has provided improved outcome in terms of minimized toxicity and high local control rates for locally advanced tumors and pathologically non-squamous cell type of tumors. Using carbon ion radiotherapy, hypofractionated radiotherapy with application of larger doses per fraction and a reduction of overall treatment times as compared to conventional radiotherapy was enabled.
Carbon↗
Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6-hydroxydopamine-lesioned rats treated with L-DOPA: implication for L-DOPA-induced dyskinesia in Parkinson's disease.
The medial globus pallidus plays a crucial role in generation of L-DOPA-induced dyskinesia in patients with Parkinson's disease. The 6-hydroxydopamine-lesioned rat exhibiting behavioral sensitization to L-DOPA is one useful animal model for examining L-DOPA-induced dyskinesia. To determine neuropathological abnormality responsible for behavioral sensitization, the medial globus pallidus and the substantia nigra reticulata in 6-hydroxydopamine-lesioned rats treated with L-DOPA were examined. Intermittent L-DOPA treatment induced hypertrophy of the lesioned-side of medial globus pallidus and substantia nigra reticulata of 6-hydroxydopamine-lesioned rats with behavioral sensitization to L-DOPA. Additionally, coadministration of a 5-HT1A receptor agonist, 8-hydroxy-2(di-n-propylamino)tetralin with L-DOPA, alleviated the hypertrophy with improvement of the behavioral sensitization. These results suggest that hypertrophy of the medial globus pallidus and substantia nigra reticulata is associated with induction of behavioral sensitization to L-DOPA in 6-hydroxydopamine-lesioned rats. Therefore, neuropathological changes corresponding to hypertrophy might underlie L-DOPA-induced dyskinesia in patients with Parkinson's disease.
Animals↗
Imprint cytologic features of pulmonary large cell neuroendocrine carcinoma: Comparison with classic large cell carcinoma.
The World Health Organization (WHO) categorized large cell neuroendocrine carcinoma (LCNEC) as a variant of large cell carcinoma in 1999. However, cytologic features of these tumors have not yet been adequately characterized. The cytologic features of 24 cases of LCNEC were analyzed and compared to the features of 16 cases of classic large cell carcinoma (CLCC). Giant cells, neutrophils and cytophagocytosis were observed more frequently in CLCC than in LCNEC (p<0.05), whereas the unclear border of tumor cells was seen more frequently in LCNEC (p<0.05). The presence of nuclear atypia, such as anisokaryosis, nuclear budding, irregularity of nuclear margins, and multinucleation (having three or more nuclei), was observed less frequently in LCNEC. Characteristic arrangements of tumor cells, such as rosette formation, and palisading, were observed only in LCNEC cases. In morphometric studies, the nuclear areas, cytoplasmic areas, and nuclear rotundity ratios were significantly higher in CLCC cells than in LCNEC cells (p<0.05). However, N/C ratios were significantly higher in LCNEC than in CLCC. LCNEC cells have less nuclear atypia than CLCC cells, and have the characteristic arrangements of tumor cells, such as palisading and rosette. It is possible to preoperatively differentiate LCNEC from CLCC by careful cytologic characterization.
Carcinoma, Large Cell↗
Acute motor axonal neuropathy rabbit model: immune attack on nerve root axons.
Macrophages in the periaxonal space and surrounding intact myelin sheath are the most prominent pathological feature of acute motor axonal neuropathy (AMAN). We describe this characteristic in nerve roots from paralyzed rabbits immunized with bovine brain ganglioside or GM1. IgG was deposited on nerve root axons. Distal nerve conduction was preserved, and late F wave components were absent during the acute phase. Initial lesions were located mainly on nerve root axons, as in human AMAN. This study thus provides supportive evidence that the rabbits constitute a model of AMAN.
Action Potentials↗
Small solitary pulmonary metastasis detected before primary sigmoid colon cancer: report of a case.
We report the case of a 60-year-old woman referred to us after chest X-ray and mobile computed tomography screening detected an 8-mm nodule in right S2. Transbronchial aspiration cytology suggested a pulmonary metastasis from colorectal cancer. Therefore, we performed a colonoscopy and found a polypoid lesion, 2 cm in diameter, in the sigmoid colon. An analysis of a biopsy specimen from this polypoid lesion confirmed adenocarcinoma. Surgical resection of the primary sigmoid colon cancer was subsequently performed, followed 4 weeks later by a right S2 segmentectomy to remove the lung metastasis. The patient is currently well without any clinical signs of recurrence, 44 months after her operation.
Adenocarcinoma↗
Dynamic movement of N100m dipoles in evoked magnetic field reflects sequential activation of isofrequency bands in human auditory cortex.
OBJECTIVE: To investigate spatiotemporal features of the isofrequency bands for 400 and 4000 Hz tones in human auditory cortex and on the hemispheric differences in the arrangement of isofrequency bands. METHODS: We recorded auditory evoked magnetic fields (AEFs) to 400 or 4000 Hz tone pips presented at right or left ear from 31 normal subjects. The dipole location for the N100m sources was successively calculated from the AEFs obtained from the hemisphere contralateral to the stimulated ear. RESULTS: In the right hemisphere, the current sources for 400 and 4000 Hz moved toward the anterolateral direction before the N100m peak, showing parallel arrangement of the isofrequency bands (4000 Hz in medial location). In the left hemisphere, the movement direction of 400 Hz dipoles was anterolateral, while that of 4000 Hz dipoles was lateral. CONCLUSIONS: This difference in the organization of isofrequency bands between right and left auditory cortices reflects distinct functional roles in auditory information processing such as pitch vs. language discrimination. SIGNIFICANCE: This work is the first to disclose isofrequency bands in human auditory cortex based on the analysis of magnetoencephalography.
Acoustic Stimulation↗
Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients.
Three genes commonly causing Charcot-Marie-Tooth disease (CMT) encode myelin-related proteins: peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32). Demyelinating versus axonal phenotypes are major issues in CMT associated with mutations of these genes. We electrophysiologically, pathologically and genetically evaluated demyelinating and axonal features of 205 Japanese patients with PMP22 duplication, MPZ mutations or Cx32 mutations. PMP22 duplication caused mainly demyelinating phenotypes with slowed motor nerve conduction velocity (MCV) and demyelinating histopathology, while axonal features were variably present. Two distinctive phenotypic subgroups were present in patients with MPZ mutations: one showed preserved MCV and exclusively axonal pathological features, while the other was exclusively demyelinating. These axonal and demyelinating phenotypes were well concordant among siblings in individual families, and MPZ mutations did not overlap among these two subgroups, suggesting that the nature and position of the MPZ mutations mainly determine the axonal and demyelinating phenotypes. Patients with Cx32 mutations showed intermediate slowing of MCV, predominantly axonal features and relatively mild demyelinating pathology. These axonal and demyelinating features were present concomitantly in individual patients to a variable extent. The relative severity of axonal and demyelinating features was not associated with particular Cx32 mutations. Median nerve MCV and overall histopathological phenotype changed little with disease advancement. Axonal features of diminished amplitudes of compound muscle action potentials (CMAPs), axonal loss, axonal sprouting and neuropathic muscle wasting all changed as disease advanced, especially in PMP22 duplication and Cx32 mutations. Median nerve MCVs were well maintained independently of age, disease duration and the severity of clinical and pathological abnormalities, confirming that median nerve MCV is an excellent marker for the genetically determined neuropathic phenotypes. Amplitude of CMAPs was correlated significantly with distal muscle strength in PMP22 duplication, MPZ mutations and Cx32 mutations, while MCV slowing was not, indicating that clinical weakness results from reduced numbers of functional large axons, not from demyelination. Thus, the three major myelin-related protein mutations induced varied degrees of axonal and demyelinating phenotypic features according to the specific gene mutation as well as the stage of disease advancement, while clinically evident muscle wasting was attributable to loss of functioning large axons.
Action Potentials↗
Evidence of neoangiogenesis and an increase in the number of proliferating cells within the bronchial epithelium of smokers.
BACKGROUND: Normal bronchial epithelium gradually acquires cellular and genetic changes that result in the formation of invasive tumors. The objective of this study was to evaluate the degree of proliferative change and the amount of neovascularization in both normal and preneoplastic lesions in smokers who were at high risk for developing lung carcinoma. METHODS: The authors studied bronchial biopsy specimens from 7 nonsmokers and 52 smokers. Immunohistochemical staining of the specimens with antibodies for the presence of p53 protein, Ki-67 and CD34 antigens, and vascular endothelial growth factor was performed. The proliferation index (PI) was assessed by immunohistochemical staining for Ki-67 antigen. RESULTS: Overexpression of p53 protein was observed frequently in regions of squamous dysplasia and in squamous cell carcinoma tissue. The PI of normal epithelium from smokers was increased compared with nonsmokers, and the difference was statistically significant (P < 0.05). The microvessel count (MC) in normal mucosa obtained from smokers was higher compared with the MC in normal mucosa obtained from nonsmokers (P < 0.05). A significant difference in MC also was observed between regions of squamous metaplasia or dysplasia with projections of capillary loops into the bronchial mucosa and similar lesions without capillary loops (P < 0.005); however, there was no difference in either the PI or the incidence of p53 overexpression between these groups. CONCLUSIONS: These results show that smoking appears to induce both a proliferative response and neovascularization in bronchial mucosa. The projection of capillary loops into the bronchial mucosa also may be a result of neovascularization occurring within the lamina propria of the bronchial wall.
Antigens, CD34↗
Imprint cytologic features of pulmonary sclerosing hemangioma: comparison with well-differentiated papillary adenocarcinoma.
BACKGROUND: Sclerosing hemangiomas (SH) of the lung are uncommon tumors and are thought to be benign. However, histogenesis of these tumors has not yet been characterized adequately. Moreover, there are few reports dealing with their cytologic features, and it is generally considered difficult to make accurate diagnoses of sclerosing hemangiomas that have a predominantly papillary pattern. METHODS: Cytologic features were analyzed for 15 sclerosing hemangiomas, and cytologic features of sclerosing hemangioma were compared with features of 22 cases of well-differentiated papillary adenocarcinoma classified as pathologic Stage 1A. RESULTS: Blood and round cells were observed more frequently in SH than in adenocarcinomas (P < 0.05), whereas necrosis was seen more frequently in adenocarcinomas than in SH (P < 0.05). The presence of nucleoli, nuclear indentations, irregularities of nuclear margins, nuclear polymorphisms, and high nuclear-cytoplasmic (NC) ratios of tumor cells were observed less frequently in SH. Polynuclear (having three or more nuclei) tumor cells were observed only in adenocarcinoma cases. In morphometric studies, the nuclear areas, cytoplasmic areas, NC ratios, long axes of nuclei, short axes of nuclei, and nuclear rotundity ratios were significantly higher in adenocarcinoma cells than in SH cells (P < 0.05). CONCLUSIONS: The presence of polymorphous cells and tumor cells with bland nuclei are characteristic cytologic findings associated with sclerosing hemangioma. It is possible to make accurate diagnoses for SH cases preoperatively by careful cytologic characterization.
Adenocarcinoma, Papillary↗
Pulmonary large cell carcinomas with neuroendocrine features are high-grade neuroendocrine tumors.
BACKGROUND: In 1999, the World Health Organization (WHO) categorized large cell carcinoma with neuroendocrine features as variants of large cell carcinoma and reclassified neuroendocrine lung tumors, especially typical and atypical carcinoid tumors. However, to date, the clinical relationship between these categories of neuroendocrine lung tumors has not been clearly defined. METHODS: We analyzed 133 cases of neuroendocrine tumors from primary lung carcinoma cases surgically resected. Using electron microscopy and immunohistochemical staining, we classified these cases as typical carcinoid (TC), atypical carcinoid (AC), large cell carcinoma with neuroendocrine features (LCNF), or small cell lung carcinoma (SCLC) based upon the WHO classification. RESULTS: TC and AC tumors were not related to smoking (p < 0.001) and, unlike LCNF, were found in younger patients (p < 0.001) without a male predominance (p < 0.001). Multivariate analysis revealed that LCNF predicted poorer overall and disease-free survivals comparable with SCLC (overall survival, p = 0.019, hazards ratio, 6.34; disease-free survival, p = 0.007, hazards ratio, 8.19). CONCLUSIONS: The prognoses of LCNF are comparable with those of SCLC, and LCNF should be classified as high-grade neuroendocrine tumors.
Adolescent↗
Correlation between endobronchial ultrasonography (EBUS) images and histologic findings in normal and tumor-invaded bronchial wall.
The aim of this study was to examine the ability of endobronchial ultrasonography (EBUS) to image the bronchial wall structure in order to assess the depth of bronchial tumor invasion. Sixty-one patients who underwent lobectomy, pneumonectomy or forceps biopsy were included in this study. In 21 patients with bronchoscopically visible bronchial malignant tumors, EBUS was performed during bronchoscopy. In the remaining 40 patients, ultrasonography was performed on the resected specimens. The EBUS findings obtained using thin ultrasonic probes (20 MHz radial scanner) were compared with the macroscopic and histologic findings of the corresponding areas in the resected specimens. When the bronchial walls were imaged while immersed in normal saline, six ultrasonically distinct layers were detected in the cartilaginous and membranous portions. A similar wall structure was imaged when EBUS was performed during bronchoscopy using a latex balloon sheath. The image of the lamina propria and submucosa was occasionally compressed and mixed with a balloon echo due to the latex balloon sheath, whereas the cartilage layer was always distinctly imaged. A good correlation was observed between the EBUS-determined cartilage thickness and the actual histologic measurement, as measured with vernier calipers. Malignant tissues were imaged as hypoechoic areas, and tumor invasion of the cartilage layer was clearly detected. In conclusion, using high-resolution (20 MHz) ultrasonic probes, the bronchial wall structure could be imaged as six distinct layers. The cartilage layer was easily identified and could be used as a reference to evaluate the rest of the bronchial wall structure.
Adult↗
Serum endostatin correlates with progression and prognosis of non-small cell lung cancer.
The relationship between non-small cell lung cancer and platelet counts, serum levels of vascular endothelial growth factor (VEGF) and endostatin, is unclear. Platelet counts and serum VEGF and endostatin levels were measured preoperatively in 99 patients with non-small cell lung cancer, and the relationship between these factors and clinicopathological features, including prognosis, was examined. Mean serum VEGF level was slightly higher in patients than in healthy subjects (P=0.23). Mean serum endostatin level was 42.4+/-40.4 ng/ml in patients compared to 16.3+/-10.3 ng/ml in healthy subjects (P=0.0003). Serum endostatin levels were significantly higher in patients with involvement greater than T2 or stage IB, compared to other patients. Platelet count and serum endostatin level greater than the median were associated with poor prognosis. Our results suggested that platelet count and serum endostatin level may be useful markers for non-small cell lung cancer.
Adenocarcinoma↗
Preoperative cytodiagnosis of very small-sized peripheral-type primary lung cancer.
To demonstrate the importance of preoperative diagnosis of pulmonary cancers presenting as peripheral small-sized solitary shadows we evaluated the results of morphologic definitive diagnosis together with various clinical factors in 91 tumors with less than 15-mm diameter resected surgically between 1983 and 1999. Histologically, these tumors consisted of 73 adenocarcinomas, nine squamous cell carcinomas, and nine other types. Regarding the pathologic stage, 57 tumors were classified in stage IA, three in IB, six in IIA, seven in IIIA, 14 in IIIB, and four in IV. Comparing various biopsy techniques, the sensitivity of preoperative cytodiagnosis was 43.7% for transbronchial brushing (n = 48), 52.9% for transbronchial forceps biopsy-stamp cytology (n = 51), 66.6% for transbronchial fine needle aspiration (n = 78), and 85.0% for percutaneous fine needle aspiration (n = 20). The overall sensitivity of preoperative cytodiagnosis was 79.0% for transbronchial biopsy (n = 81), and 87.3% for transbronchial and percutaneous biopsy (n = 87). Of 73 clinical N0 cases in which lobectomy was performed, 10 cases (13.6%) were diagnosed as between pathological degrees N1, N2 and N3. However, lung cancer cases with less than 10-mm diameter did not have lymph node metastasis. Our study of histologic differentiation showed that all cases of well-differentiated adenocarcinomas (n = 20) were pathological degree N0. The overall sensitivity of preoperative diagnosis increased to 89.1% in cases (n = 74) of tumors with 11-15-mm diameter. The sensitivity of cytodiagnosis for peripheral small-sized primary lung cancers is high, and we can estimate histological differentiation based on the cytological findings. Therefore, cytodiagnosis is an effective and indispensable diagnostic method for determination of the optimal treatment approach, including approaches such as intentionally limited resection.
Adult↗
Alpha-fetoprotein-producing lung carcinoma: report of three cases.
Three cases of alpha-fetoprotein (AFP)-producing lung carcinoma were studied histologically and immunohistochemically. Samples were obtained from two men and one woman who ranged in age from 64 to 71 years. Serum AFP levels for the three samples were 9826, 74.4 and 24.3 ng/mL. One case was classified as stage IIIA and two as stage IIIB. Two cases were diagnosed as large cell neuroendocrine carcinoma, and AFP expression was detected immunohistochemically. One of these samples showed differentiation to a hepatoid carcinoma, while the other was combined with a squamous cell carcinoma. The remaining case was a squamous cell carcinoma, and AFP was detected in only some of the tumor cells. All patients died within 2 years. The Ki-67 labeling indices of the AFP-producing pulmonary carcinomas (30.2 +/- 4.6%) were significantly higher than those of AFP-negative pulmonary carcinomas (P < 0.05). The high proliferative activity, advanced stage at presentation, vascular endothelial growth factor expression and vascular invasion observed in these tumors may explain the poor prognosis of AFP-producing lung carcinomas.
Aged↗